Bronchioalveolar stem cells (BASCs) located at the bronchioalveolar-duct junction (BADJ) are stem cells residing in alveoli and terminal bronchioles that can self-renew and differentiate into alveolar type (AT)-1 cells, AT-2 cells, club cells, and ciliated cells. Following terminal-bronchiole injury, BASCs increase in number and promote repair. However, whether BASCs can be differentiated from mouse-induced pluripotent stem cells (iPSCs) remains unreported, and the therapeutic potential of such cells is unclear. We therefore sought to differentiate BASCs from iPSCs and examine their potential for use in the treatment of epithelial injury in terminal bronchioles. BASCs were induced using a modified protocol for differentiating mouse iPSCs into AT-2 cells. Differentiated iPSCs were intratracheally transplanted into naphthalene-treated mice. The engraftment of BASCs into the BADJ and their subsequent ability to promote repair of injury to the airway epithelium were evaluated. Flow cytometric analysis revealed that BASCs represented ~ 7% of the cells obtained. Additionally, ultrastructural analysis of these iPSC-derived BASCs via transmission electron microscopy showed that the cells containing secretory granules harboured microvilli, as well as small and immature lamellar body-like structures. When the differentiated iPSCs were intratracheally transplanted in naphthalene-induced airway epithelium injury, transplanted BASCs were found to be engrafted in the BADJ epithelium and alveolar spaces for 14 days after transplantation and to maintain the BASC phenotype. Notably, repair of the terminal-bronchiole epithelium was markedly promoted after transplantation of the differentiated iPSCs. Mouse iPSCs could be differentiated in vitro into cells that display a similar phenotype to BASCs. Given that the differentiated iPSCs promoted epithelial repair in the mouse model of naphthalene-induced airway epithelium injury, this method may serve as a basis for the development of treatments for terminal-bronchiole/alveolar-region disorders.
Masami Morimoto, Hiroaki Toba, Mariko Aoyama, Misako Nakagawa, Hirokazu Takechi, Takahiro Yoshida and Akira Tangoku : Phase 1 Dose-Escalation Study of Triweekly Nab-Paclitaxel Combined With S-1 for HER2-Negative Metastatic Breast Cancer, Clinical Breast Cancer, Vol.20, No.6, 448-453, 2020.
(要約)
To evaluate the efficacy, toxicity, maximum tolerated dose, and recommended dose of triweekly nab-paclitaxel (nab-PTX) and S-1 combination chemotherapy for patients with metastatic breast cancer. This phase 1 study was conducted with a standard 3 + 3 dose escalation design. Every 3 weeks, the patients received nab-PTX at 180-260 mg/m on day 1 and S-1 at 65-80 mg/m daily on days 1 to 14. Ten HER2-negative metastatic breast cancer patients were enrolled; their median number of prior chemotherapy regimens was 3. Dose-limiting toxicity was observed in the first patient assigned to level 4; grade 4 febrile neutropenia and grade 3 neurotoxicity such as needing a wheelchair occurred. Therefore, an additional patient was not assigned to level 4. The maximum tolerated dose was considered level 4 (260 mg/m nab-PTX with 80 mg/m S-1). The recommended dose determined was level 3 (220 mg/m nab-PTX with 80 mg/m S-1). The response rate was 60.0%. The disease control rate was 70.0%. This combination chemotherapy therapy was feasible and safe for patients with HER2-negative metastatic breast cancer.
Seiya Inoue, Takahiro Yoshida, Takeshi Nishino, Masakazu Goto, Yoshihito Furukita, Yota Yamamoto, Satoshi Fujiwara, Takuya Minato, Hiroyuki Sumitomo, Yasuhiro Yuasa, Hiromitsu Takizawa and Akira Tangoku : The sterno-tracheal distance is an important factor of anastomotic leakage of retrosternal gastric tube reconstruction after esophagectomy, Esophagus, Vol.17, No.3, 264-269, 2020.
(要約)
Anastomotic leakage (AL) is a serious complication after esophagectomy. The retrosternal (RS) route has been selected majorly to reduce reflux and related pneumonia and considering mediastinal recurrences. AL has been developed more in RS than posterior mediastinal (PM) route reconstruction. Therefore, we suspected the sterno-tracheal distance (STD) might be related to AL and started the selection according to the STD from 2009. A total of 221 patients who underwent a subtotal esophagectomy with gastric tube reconstruction during January 2004-April 2017 were investigated. The patients were classified into the 'after STD selection' (A; n = 144) group and the 'before STD selection' (B, n = 77) group. The incidences of and the risk factors for AL between the two groups were compared. The incidence of AL was high in the B group (18.2%), and 78.6% of the patients who developed AL were treated with RS route reconstruction. The median STDs of the patients with AL and no AL were 10.3 mm and 14.5 mm, respectively (p = 0.001). These results demonstrated that the STD was a risk factor for AL in the RS route. Based on these results, 13 mm was set as the cutoff value. After STD selection, the median STD increased from 14.0 to 17.3 mm (p = 0.001), and the incidence of AL decreased significantly from 26.2 to 11.1% in the RS route (p = 0.037). The STD was the independent risk factor for AL in the RS route. RS route reconstruction should be avoided for the patients with STD < 13 mm.
Naoki Miyamoto, Mitsuteru Yoshida, Mitsuhiro Tsuboi, Kenji Otsuka, Yoshimi Bando, Takumi Kakimoto, Naoya Kawakita, Hiromitsu Takizawa, Kazuya Kondo and Akira Tangoku : A case of long-term unchanged calcifying fibrous tumor, General Thoracic and Cardiovascular Surgery, Vol.68, No.12, 1587-1590, 2020.
(要約)
A calcifying fibrous tumor (CFT) is a rare benign tumor that may occur in any part of the body. We report the case of an asymptomatic 21-year-old woman with thoracic tumors. Chest computed tomography showed multiple masses in the left costophrenic angle. As we were unable to diagnose the tumor with a CT-guided needle biopsy, we performed a thoracoscopic biopsy. We found smooth multilobulated masses on the pleura and multiple small nodules around the main tumors. Partial resection of the tumor was performed by VATS. Histological examination revealed that the tumor had hypocellular fibrosclerotic tissue and distributed psammomatous calcifications with inflammatory infiltrates. Immunohistochemistry demonstrated that the spindle cells were partially positive for CD34 and CD99, but negative for anaplastic lymphoma kinase-1, smooth muscle actin, BCL-2, STAT6, and S-100 protein. The tumor was diagnosed as CFT. The patient's postoperative recovery was uneventful, and no progression of the lesions was observed during follow-up.
Naoya Kawakita, Hiroaki Toba, Yukikiyo Kawakami, Hiromitsu Takizawa, Yoshimi Bando, Hideki Otsuka, Daisuke Matsumoto, Mika Takashima, Mitsuhiro Tsuboi, Mitsuteru Yoshida, Kazuya Kondo and Akira Tangoku : Use of a prognostic risk score that aggregates the FDG-PET/CT SUVmax, tumor size, and histologic group for predicting the prognosis of pStage I lung adenocarcinoma, International Journal of Clinical Oncology, Vol.25, No.6, 1079-1089, 2020.
(要約)
pStage I includes clinicopathologically diverse groups. This study aimed to identify the prognostic factors for pStage I lung adenocarcinoma. We retrospectively reviewed 208 patients with pStage I adenocarcinomas who underwent curative resection in our institute between 2006 and 2013. The maximum standardized uptake value (SUVmax) on [F18]-fluoro-deoxy-D-glucose positron emission tomography-computed tomography (PET/CT) was evaluated. Adenocarcinomas were categorized into the following histologic groups: group 0 (minimally invasive adenocarcinoma and lepidic predominant adenocarcinoma), group 1 (papillary predominant adenocarcinoma), and group 2 (acinar predominant adenocarcinoma and all the remaining subtypes). We assessed the relationship between disease-free survival (DFS) and clinicopathological factors. Multivariate analysis of DFS demonstrated that SUVmax > 3.0 (p < 0.001), total tumor size > 20 mm (p = 0.016), and histologic groups (p < 0.05) were independent prognostic factors. The prognostic risk score (PRS) was calculated using the following equation: PRS = SUVmax (≤ 3.0: 0 point, > 3.0: 2 points) + total tumor size (≤ 20 mm: 0 point, > 20 mm: 1 point) + histologic group (group 0: 0 point, group 1: 1 point, group 2: 2 points). Patients were divided into the following three risk groups: low-risk (PRS 0-2 points, n = 136), intermediate-risk (PRS 3-4 points, n = 49), and high-risk groups (PRS 5 points, n = 13). The 5-year DFS rates were 93.2%, 50.6%, and 30.8% for the low-, intermediate-, and high-risk groups, respectively (p < 0.001). The PRS aggregating the FDG-PET/CT SUVmax, total tumor size, and histologic group predicts the prognosis of pStage I lung adenocarcinoma.
Seiya Inoue, Takahiro Yoshida, Takeshi Nishino, Masakazu Goto, Kouhei Nishioka, Keisuke Fujimoto, Mariko Aoyama, Daisuke Matsumoto, Hiromitsu Takizawa and Akira Tangoku : Safe central venous catheters for esophageal cancer treatment, The Journal of Medical Investigation : JMI, Vol.67, No.3,4, 298-303, 2020.
(要約)
Introduction : Central venous catheter (CVC) use is essential for treating esophageal cancer. Peripherally inserted central catheters (PICC) are commonly used recently for improved patient comfort and safety. We compared centrally inserted central catheters (CICC) and PICC insertions and examined their safety. Methods : We retrospectively investigated complications at the catheter insertion and post-insertion for 199 patients' esophageal cancer treatment (CICC : 45, PICC : 154) from 2013 to 2018. In addition, we summarized the results of catheter tip culture. Results : No serious complications occurred at the catheter insertion in either group. The rate of complications at catheter insertion was 5.8% for PICC and 6.7% for CICC patients. Post-insertion complications were observed in 6.5% and 11.1% of patients with PICC and CICC, respectively, and this difference was not significant. The incidence of catheter-related blood stream infection (CRBSI) was significantly lower in PICC than CICC patients (0.3 vs. 1.8 / 1,000 catheter-days ; p = 0.029). Catheter-related thrombosis was observed in PICC : 0.5 and CICC : 0.6, and occlusion due to blood flow reversal was observed in PICC : 0.5 and CICC : 0.6. Conclusion : PICCs are safer and more effective than CICCs for the treatment of esophageal cancer, and reduce the incidence of CRBSI. We hope to standardize the insertion procedures, conventionalize techniques, and establish training systems. J. Med. Invest. 67 : 298-303, August, 2020.
Reina Kishibuchi, Kazuya Kondo, Shiho Soejima, Mitsuhiro Tsuboi, Koichiro Kajiura, Yukikiyo Kawakami, Naoya Kawakita, Toru Sawada, Hiroaki Toba, Mitsuteru Yoshida, Hiromitsu Takizawa and Akira Tangoku : DNA methylation of GHSR, GNG4, HOXD9 and SALL3 is a common epigenetic alteration in thymic carcinoma, International Journal of Oncology, Vol.56, No.1, 315-326, 2019.
(要約)
Thymic epithelial tumors comprise thymoma, thymic carcinoma and neuroendocrine tumors of the thymus. Recent studies have revealed that the incidence of somatic non-synonymous mutations is significantly higher in thymic carcinoma than in thymoma. However, limited information is currently available on epigenetic alterations in these types of cancer. In this study, we thus performed genome-wide screening of aberrantly methylated CpG islands in thymoma and thymic carcinoma using Illumina HumanMethylation450 K BeadChip. We identified 92 CpG islands significantly hypermethylated in thymic carcinoma in relation to thymoma and selected G protein subunit gamma 4 (GNG4), growth hormone secretagogue receptor (GHSR), homeobox D9 (HOXD9) and spalt like transcription factor 3 (SALL3), which are related to cancer. We examined the promoter methylation of 4 genes in 46 thymic epithelial tumors and 20 paired thymus tissues using bisulfite pyrosequencing. Promoter methylation was significantly higher in thymic carcinoma than in thymoma and revealed a high discrimination between thymic carcinoma and thymoma in all 4 genes. Promoter methylation was higher in thymic carcinoma than in the thymus. No significant differences were observed in the promoter methylation of GNG4, HOXD9, or SALL3 between thymoma and the thymus. The promoter methylation of the 4 genes was not significantly higher in advanced-stage tumors than in early-stage tumors in all thymic epithelial tumors. Among the 4 genes, relapse-free survival was significantly worse in tumors with a higher DNA methylation than in those with a lower DNA methylation in all thymic epithelial tumors. Moreover, relapse-free survival was significantly worse in thymomas with a higher DNA methylation of HOXD9 and SALL3 than in those with a lower DNA methylation. On the whole, the findings of this study indicated that the promoter methylation of cancer-related genes was significantly higher in thymic carcinoma than in thymoma and the thymus. This is a common epigenetic alteration of high diagnostic value in thymic carcinoma and may be involved in the carcinogenesis of thymic carcinoma. However, epigenetic alterations in the 3 genes, apart from GHSR, are not involved in the tumorigenesis of thymoma.
Mitsuhiro Tsuboi, Kazuya Kondo, Shiho Soejima, Koichiro Kajiura, Naoya Kawakita, Hiroaki Toba, Yukikiyo Kawakami, Mitsuteru Yoshida, Hiromitsu Takizawa and Akira Tangoku : Chromate exposure induces DNA hypermethylation of the mismatch repair gene MLH1 in lung cancer, Molecular Carcinogenesis, Vol.59, No.1, 24-31, 2019.
(要約)
Hexavalent chromium is recognized as a human carcinogen. Our previous studies revealed that lung cancer (LC) in chromate-exposed workers (chromate LC) had molecular features of frequent microsatellite instability (MSI), repression of MLH1 level, and aberrant DNA methylation of several tumor-suppressor genes, including MLH1. In the present study, we quantitatively investigated MLH1-promoter methylation status using bisulfite pyrosequencing of paired tumorous/nontumorous tissues from chromate and nonchromate LCs to determine the effect of chromate exposure on MLH1-promoter methylation. The methylation level of MLH1 promoter was significantly higher in chromate LC tumors (P < .001) than nonchromate LC tumors and, among chromate LC, significantly higher in tumorous tissue than nontumorous tissue (P = .004). Moreover, the methylation level of MLH1 promoter in normal lung tissue tended to be higher in chromate LC than nonchromate LC (P = .062). In addition, LC with reduced levels of MLH1 showed significantly higher methylation levels of MLH1 promoter than LC exhibiting normal MLH1 levels (P = .019). Moreover, immunohistochemical analyses determined that levels of SUV39H1, an H3K9me2-related methyltransferase, were higher in chromate LC than nonchromate LC (P = .076). Furthermore, we evaluated three DNA double-strand break-repair genes (MRE11, RAD50, and DNA-PKcs) as possible targets of MSI by fragment-length polymorphism analysis, revealing the mutation frequency of RAD50 as significantly higher in chromate LC than nonchromate LC (P = .047). These results suggest that chromate exposure might induce MLH1 hypermethylation in LC as a mechanism of chromate-induced carcinogenesis.
Takumi Sakurada, Sanako Bando, Yoshito Zamami, Kenshi Takechi, Masayuki Chuma, Mitsuhiro Goda, Yasushi Kirino, Toshimi Nakamura, Kazuhiko Teraoka, Masami Morimoto, Akira Tangoku and Keisuke Ishizawa : Prophylactic administration of granulocyte colony-stimulating factor in epirubicin and cyclophosphamide chemotherapy for Japanese breast cancer patients: a retrospective study., Cancer Chemotherapy and Pharmacology, Vol.84, No.5, 1107-1114, 2019.
(要約)
The incidence rate of FN was 23.9%. In patients who received G-CSF as primary prophylaxis, FN expression was completely suppressed. The incidence rate of severe leucopenia/neutropenia, emergency hospitalization, and the use of antimicrobial agents were low in patients receiving primary prophylaxis with G-CSF compared with those not receiving G-CSF (27.3% vs. 64.8%, 9.1% vs. 27.3%, and 27.3% vs. 71.6%, respectively). Furthermore, in all patients who received primary prophylaxis with G-CSF, a relative dose intensity > 85% using EC therapy was maintained.
Mitsuhiro Tsuboi, Kazuya Kondo, Kiyoshi Masuda, Shoichiro Tange, Koichiro Kajiura, Tomohiro Kohmoto, Hiromitsu Takizawa, Issei Imoto and Akira Tangoku : Prognostic significance of GAD1 overexpression in patients with resected lung adenocarcinoma, Cancer Medicine, Vol.8, No.9, 4189-4199, 2019.
(要約)
In a previous genome-wide screening, we identified hypermethylated CpG islands around glutamate decarboxylase 1 (GAD1) in lung adenocarcinoma (LADC). In this study, we aimed to investigate the methylation and expression status of GAD1 and its prognostic value in patients with LADC. GAD1 methylation and mRNA expression status were analyzed using 33 tumorous and paired non-tumorous LADC samples and publicly available datasets. The prognostic value of GAD1 overexpression was investigated using publicly available datasets of mRNA levels and 162 cases of LADC by immunohistochemistry. The methylation and mRNA expression levels of GAD1, each having a positive correlation, were significantly higher in LADC tumors than in paired non-tumorous tissues. LADC patients with higher GAD1 mRNA expression showed significantly poorer prognosis for overall survival in publicly available datasets. Higher immunoreactivity of GAD1 was significantly associated with the pathological stage, pleural invasion, lymph vessel invasion, and poorer prognosis for cancer-specific and disease-free survival. Multivariate analysis revealed that GAD1 protein overexpression is an independent prognosticator for disease-free survival. GAD1 mRNA and protein expression levels were significant prognostic factors in LADC, suggesting that they might be useful biomarkers to stratify patients with worse clinical outcomes after resection.
A.A.Ali Eman, Hiromitsu Takizawa, Naoya Kawakita, Toru Sawada, Mitsuhiro Tsuboi, Hiroaki Toba, Mika Takashima, Daisuke Matsumoto, Mitsuteru Yoshida, Yukikiyo Kawakami, Kazuya Kondo, El-Badrawy Khairy Mohammad and Akira Tangoku : Transbronchial Biopsy Using an Ultrathin Bronchoscope Guided by Cone-Beam Computed Tomography and Virtual Bronchoscopic Navigation in the Diagnosis of Pulmonary Nodules, Respiration, Vol.98, No.4, 321-328, 2019.
(要約)
Transbronchial biopsy is a safe diagnostic approach for patients with peripheral pulmonary lesions; however, the diagnostic yield is low. This study was conducted to evaluate the feasibility and diagnostic yield of transbronchial biopsy using the combination of an ultrathin bronchoscope, virtual bronchoscopic navigation (VBN), and cone-beam computed tomography (CBCT). Patients with peripheral pulmonary lesions, no >30 mm, with the responsible bronchus, were prospectively included. An ultrathin bronchoscope and biopsy forceps were advanced to the target bronchus under VBN, 2D-fluoroscopy, and CBCT. We categorized the CBCT findings before biopsy into 3 types according to positions of the target lesion and forceps (CBCT target-forceps sign). In type A, the forceps reached the inside of the target lesion. In type C, the forceps could not reach the lesion. When the CBCT findings could not be categorized into either type A or C, the sign was categorized as type B. Although the target lesions were invisible by conventional C-arm fluoroscopy in 29 patients, CBCT visualized all 40 lesions. The overall diagnostic yield was 90.0%, and diagnostic yields for malignant and benign lesions were 92.0 and 86.7%, respectively. Diagnostic yields for CBCT target-forceps sign types A, B, and C were 100, 75.0, and 0%, respectively. Four undiagnosed patients proceeded to other diagnostic procedures based on the CBCT target-forceps sign (type B: n = 2, type C: n = 2) and were correctly diagnosed without delay. Transbronchial biopsy using an ultrathin bronchoscope guided by CBCT and VBN showed a very high yield in the diagnosis of pulmonary nodules.
It was suggested long ago that regional cooperation is necessary for cancer patients. Both doctors in base hospitals and community doctors understand the importance of such cooperation. Here we report the results of our widely distributed questionnaire designed to clarify the division of physicians' roles and to strengthen the relationships between base hospital and community doctors. The questionnaire asks whether community doctors can accept cancer patients and what types of medical treatment the doctors can provide for patients with esophageal cancer, lung cancer, breast cancer, and thyroid cancer. The doctors in 289 of 550 (53%) facilities completed and returned the questionnaire. About half of the community doctors responded that they can accept patients with any of the four cancers and can provide most types of the necessary medical examinations and treatments in their daily practices. Most of the community doctors indicated that they could not provide some anti-cancer drugs and supportive drug therapies for breast cancer patients. The development and implementation of a clinical pathway system could enable the participation of more community doctors and base hospital doctors. Although our findings are preliminary, they will contribute to a foundation for building better regional corporative relationships with community doctors who treat cancer patients.
(キーワード)
A widely distributed questionnaire / Regional corporation / Cancer patient / Community Doctor
Naoya Kawakita, Hiromitsu Takizawa, Toru Sawada, Daisuke Matsumoto, Mitsuhiro Tsuboi, Hiroaki Toba, Mitsuteru Yoshida, Yukikiyo Kawakami, Kazuya Kondo and Akira Tangoku : Indocyanine green fluorescence imaging for resection of pulmonary metastasis of hepatocellular carcinoma, Journal of Thoracic Disease, Vol.11, No.3, 944-949, 2019.
(要約)
Indocyanine green (ICG) accumulates in hepatocellular carcinoma (HCC), and tumor fluorescence can be observed under irradiation with near infrared light (NIR). This study investigated the clinical utility of ICG fluorescence imaging during resection of pulmonary metastases of HCC. From April 2010 to June 2018, six patients with suspected pulmonary metastasis of HCC were enrolled prospectively. Prior to surgery, all patients underwent the ICG hepatic function test following intravenous administration of ICG (0.5 mg/kg body weight). During surgery, metastatic HCC was identified by observation of ICG fluorescence, allowing assessment of the surgical margin. Tumor fluorescence was also evaluated on cut sections. A total of 11 metastatic HCCs were resected in six patients at nine operations. Eight lesions were removed by wedge resection and 3 lesions were managed by lobectomy. During surgery, tumor fluorescence could be confirmed through the visceral pleura in 6 out of 7 lesions treated by wedge resection, while NIR irradiation was difficult for 1 lesion. For these 6 lesions, the median distance from the tumor to the visceral pleura and the median surgical margin were 0 mm (range, 0-2 mm) and 14 mm (range, 11-17 mm), respectively. When cut sections were examined, all tumors emitted fluorescence. All lesions were histologically confirmed to be metastatic HCC. In patients with pulmonary metastasis of HCC, ICG fluorescence imaging is useful for identifying the tumor and securing its margin when the lesion is peripheral and wedge resection is planned.
Koichiro Kajiura, Shoichiro Takao, Kawano Naoko, Toru Sawada, Mitsuhiro Tsuboi, Hiroaki Toba, Mitsuteru Yoshida, Hiromitsu Takizawa, Akira Tangoku and Kazuya Kondo : Evaluation of the components of mediastinal cystic lesions using imaging techniques, The Journal of Medical Investigation : JMI, Vol.66, No.1,2, 106-111, 2019.
(要約)
To identify and differentiate patients with mediastinal cysts from those with cystic tumors requiring surgery. A total of 36 patients with mediastinal cystic lesions were enrolled. The patients were separated into two groups based on pathological findings : those with mediastinal cysts (n=23) and those with mediastinal tumors (n=13). The cystic components were measured using imaging parameters including mean computed tomography (CT) value, apparent diffusion coefficient (ADC), T1 signal intensity ratio (T1SIratio), and T2 signal intensity ratio (T2SI-ratio), acquired from magnetic resonance imaging (MRI) ; and standardized maximum uptake value (SUVmax) fromF-fluorodeoxyglucose positron emission tomography/computed tomography (F-FDG PET/CT). Both groups were statistically compared. Comparative parameters between the cysts and tumors revealed the following ratios : CT value, 40.9?21.2 versus (vs) 24.8?12.9 (p = 0.019) ;SUVmax, 1.18?0.50 vs 4.32?3.52 (p = 0.003) ; ADC, 3.46?0.96 vs 2.68?0.74 (p = 0.022) ; T1SI-ratio, 1.06?0.60 vs 1.35? 0.92 (p = 0.648) ; T2SI-ratio, 5.40?1.80 vs 4.33?1.58 (p = 0.194). However, there was no correlation between FDG uptake and ADC value. SUVmax fromF-FDG PET/CT and ADC derived from MRI were effective in facilitating preoperative diagnosis to differentiate mediastinal cysts from tumors. However, these examinations may be complementary to one another, not dominant. J. Med. Invest. 66 : 106-111, February, 2019.
Chisato Tonoiso, Hitoshi Ikushima, Akiko Kubo, Takashi Kawanaka, Shunsuke Furutani, Takaharu Kudoh, Takahiro Yoshida, Hiroshi Miyamoto, Masafumi Harada, Tetsuji Takayama and Akira Tangoku : Clinical outcomes and prognostic factors of definitive radiotherapy for esophageal cancer, The Journal of Medical Investigation : JMI, Vol.66, No.1, 2, 99-105, 2019.
(要約)
Purpose To assess the treatment results of definitive radiotherapy for esophageal cancer at Tokushima University Hospital and clarify the prognostic factors. Methods Seventy consecutive patients with esophageal cancer who underwent definitive radiotherapy between May 2004 and March 2012 were included in the present study. Local control rate, overall survival rate, and radiation morbidity were examined and univariate and multivariate analyses were performed to investigate prognostic factors. Results The 5-yearoverall survival rates of stages I, II, III, and IVA were 81%, 71%, 0%, and 9%, respectively. Performance status, clinical stage, and neoadjuvant chemotherapy were significant prognostic factors. A past history of interstitial pneumonia was associated with severe radiation-induced lung injury. Conclusions Patients who underwent definitive chemoradiotherapy for esophageal cancer in stage I/II showed good prognosis. However, treatment results of the patients in stage III/IV were not satisfactory, and those who could not undergo surgery after neoadjuvant chemotherapy had the worst prognosis.J.Med.Invest.66:99-105, February, 2019.
(キーワード)
esophageal cancer / radiotherapy / chemoradiotherapy
Misako Nakagawa, Mayumi Ikeuchi, Masami Morimoto, Hirokazu Takechi, Hiroaki Toba, Takahiro Yoshida, Kazumasa Okumura, Naoki Hino, Aya Nishisho and Akira Tangoku : Phase II Study of S-1 Combined With Low-Dose Docetaxel as Neoadjuvant Chemotherapy for Operable Breast Cancer Patients (N-1 Study), Clinical Breast Cancer, Vol.S1526-8209, No.18, 30262-30263, 2019.
(要約)
To improve the pathological complete response (pCR) rate, we devised new neoadjuvant chemotherapy. Efficacy and safety of the oral fluoropyrimidine derivative S-1 (Taiho Pharmaceutical Co, Tokyo, Japan) combined with low-dose docetaxel (S-1+DOC) were evaluated. Patients were treated with docetaxel (40 mg/m intravenously on day 1) and S-1 (40 mg/m orally twice per day on days 1-14) every 3 weeks for 4 cycles. In accord with the Response Evaluation Criteria In Solid Tumors version 1.1 criteria, the patients who showed a complete response (CR) underwent surgery, and those who achieved a partial response (PR) underwent 4 more cycles of S-1+DOC. Patients who achieved stable disease (SD) or progressive disease (PD) received EC (epirubicin and cyclophosphamide) or HT (trastuzumab and paclitaxel) according to their HER2 status. The primary end point was the pCR rate. Ninety-four patients entered the study. After 4 cycles of S-1+DOC, CR was noted in 5 patients, PR in 57, SD in 18, and PD in 3. Of the patients who achieved SD and PD, 12 received EC, and 9 received HT. Among the 83 assessable patients, the pCR rate was 34.9%, and the response rate was 80.7%. The pCR rates were 19.5% in the luminal type group, 53.8% in the luminal HER2 group, 46.1% in the HER2 group, and 50.0% in the triple-negative group. The S-1+DOC regimen in this study could be well tolerated and a new candidate neoadjuvant chemotherapy in operable breast cancer patients. It is also expected to be effective even in patients with luminal type disease. However, further randomized control trials are needed to ascertain whether pCR can contribute to favorable outcomes.
Naoya Kawakita, Hiroaki Toba, Shoji Sakiyama, Mitsuhiro Tsuboi, Hiromitsu Takizawa and Akira Tangoku : A case of thoracoscopic medial basal segmentectomy, International Journal of Surgery Case Reports, Vol.55, 15-17, 2019.
(要約)
Isolated resection of the medial basal segment (S7) is uncommon because of its small volume, and S7 segmentectomy is considered to be difficult due to anatomical variation. We report a case of successful thoracoscopic S7 segmentectomy. A 56-year-old man was referred to our hospital with suspected pulmonary metastasis of rectal cancer. A 6-mm nodule was detected in S7. A7 and B7 branched from the basal segmental artery and bronchus, respectively, to run ventral to the inferior pulmonary vein. This made it possible to isolate A7 and B7 by an approach via the interlobar fissure. In addition, V7a and V7b were easily isolated from inferior pulmonary vein. The intersegmental plane was indicated by V7b and was transected along a demarcation line identified by using selective oxygenation via B7. B7 most commonly branches from the basal bronchus and A7 from the basal artery to run ventral to the inferior pulmonary vein. With this anatomical type, when the surgeon approaches via the interlobar fissure during surgery, A7 is identified first, B7 is seen behind A7, and the IPV is posterior to B7. Since the intersegmental plane is located ventral to the IPV, segmentectomy can be completed via the interlobar fissure approach. In patients with this pattern of pulmonary artery and bronchial anatomy, isolated S7 segmentectomy is a feasible treatment option.
Haruka Takasugi, Takahiro Yoshida, Takeshi Nishino, Masakazu Goto, Seiya Inoue, Daisuke Matsumoto, Tomohiro Inui, Hiromitsu Takizawa, Hideo Tsuzuki, Toshikatsu Taniki and Akira Tangoku : Acase of advanced colon cancer arising from a colonic graft foran esophago-bronchial fistula : A case report., The Journal of Medical Investigation : JMI, Vol.66, No.1.2, 190-193, 2019.
(要約)
Neoplasm of a colonic graft after esophageal reconstruction is rare. We treated a colon cancer patient who developed malignancy in a colonic graft after esophagectomy and reconstruction through a retrosternal route. A male had undergone esophagectomy in his 50s due to a benign esophago-bronchial fistula. His dysphagia became exacerbated 20 years later, and further examinations showed a circumferential tumor on the esophagocolonic anastomosis. He underwent resection of the colonic graft adenocarcinoma with median sternotomy after neoadjuvant chemotherapy. Gastric tube reconstruction was performed through a retrosternal route. This report should be informative in terms of making decisions from an initial reconstruction to follow-up and choosing a therapeutic strategy for colonic graft cancer in the future. J. Med. Invest. 66 : 190-193, February, 2019.
Mariko Aoyama, Hiromitsu Takizawa, Mitsuhiro Tsuboi, Shinichi Yamasaki, Yoshihiro Tsuruo and Akira Tangoku : Surgical training in video-assisted neck surgery-based thyroidectomy using fresh frozen human cadavers., The Journal of Medical Investigation : JMI, Vol.66, No.3.4, 293-296, 2019.
(要約)
Endoscopic surgery has been introduced in various surgical fields. Endoscopic surgery requires different skills from open surgery due to the restricted surgical field and difficulty in identifying anatomical structures from certain viewpoints. Therefore, surgeons need to undergo sufficient surgical training before performing such surgery in the clinical setting. We examined the utility of fresh frozen human cadavers for surgical training aimed at introducing video-assisted neck surgery (VANS) at our department. First, we performed surgical training using fresh human cadavers four times. Next, we performed hemi-thyroidectomy with VANS in 5 clinical patients. After the cadaver training and the actual surgery, the surgeons evaluated each step of the surgical procedure using a 3-point scale. In the cadaver training, the scores for steps : creation of a subcutaneous tunnel and lifting up the skin flap and pre-thyroid muscles were higher than other steps. And a tracheal injury occurred as a complication. However, we were able to recognize anatomical structures under the endoscopic view. And it was also useful for confirming the role of surgical staff and simulating the placement of surgical equipment. Surgical training using fresh frozen human cadavers was effective at introducing a new surgical method. J. Med. Invest. 66 : 293-296, August, 2019.
A 60s female complained of right thigh pain caused by bone metastasis from advanced breast cancer. She was introduced to our ward for systemic therapy with palliative radiation to painful osteolytic lesion in the right femur. She suddenly complained of serious pain and motility disturbance in the right upper-extremity two days after her admission. Magnetic resonance imaging(MRI)suggested bone metastasis in the 3rd cervical vertebra which compressed spinal cord. We discussed about an optimal treatment with the orthopedic surgeon and the radiation therapeutic physician, and laminectomy was scheduled promptly. She also had a right femur fracture a day before her planed laminectomy, so she underwent osteosynthesis of the femur together with laminectomy of the cervical vertebra. She also received the irradiation to the 3rd cervical vertebra and the shaft of right femur. She became able to eat with a spoon by herself and her activity of daily living(ADL)have fully recovered by daily rehabilitation. She is receiving chemotherapy in our out-patient clinic now. We recognized that an emergent oncological treatment for the spinal decompression by the bone metastasis could improve the patients' quality of life(QOL)to avoid the permanent paralysis and also their prognoses.
Satomi Moriyama, Daisuke Hinode, Masami Yoshioka, Yuka Sogawa, Takeshi Nishino, Akira Tangoku and Daniel Grenier : Impact of the use of Kampo medicine in patients with esophageal cancer during chemotherapy: a clinical trial for oral hygiene and oral condition, The Journal of Medical Investigation : JMI, Vol.65, No.3,4, 184-190, 2018.
(要約)
The aim of this study was to investigate the impact of the use of two Kampo medicines on oral mucositis, tongue coating bacteria, and gingiva condition in patients with esophageal cancer undergoing chemotherapy. Twenty-three esophageal cancer patients who receive chemotherapy at Tokushima University Hospital, were included. The participants, who received professional oral healthcare, were randomly divided into three groups:7 subjects received Daiokanzoto sherbets, 7 subjects received Hangeshashinto sherbets, and 9 subjects received nothing (control). The numbers of total bacteria and specific periodontopathogenic bacteria in tongue coating were determined in addition to clinical parameters. No difference on the onset of oral mucositis was found among the three groups. However, tongue coating index, gingival index (GI), plaque index, the number of total bacteria, Fusobacterium nucleatum and Campylobacter rectus were decreased during chemotherapy. More specifically, GI as well as the number of F. nucleatum and C. rectus were decreased significantly in the Daiokanzoto group when compared to the control group (psize 8 < 0.05). No such differences were observed for the group receiving Hangeshashinto. This clinical trial showed that Daiokanzoto might be effective in attenuating gingival inflammation and reducing the levels of periodontopathogenic bacteria in patients with esophageal cancer. J. Med. Invest. 65:184-190, August, 2018.
Mitsuhiro Tsuboi, Hiromitsu Takizawa, Takahiro Yoshida and Akira Tangoku : Mediastinal Parathyroidectomy Using a Cervical Approach Under a Pneumomediastinum, Seminars in Thoracic and Cardiovascular Surgery, Vol.30, No.4, 472-474, 2018.
(要約)
Video-assisted thoracoscopic surgery (VATS) and robotic surgery are minimally invasive surgeries for mediastinal parathyroid adenomas. However, a transthoracic approach is often difficult in the cervicothoracic transition area because of the limited visual field. We report a novel minimally invasive surgery for an ectopic parathyroid adenoma in the middle mediastinum using a cervical approach under a pneumomediastinum.
Mitsuhiro Tsuboi, Hiromitsu Takizawa, Takahiro Yoshida and Akira Tangoku : Mediastinal Parathyroidectomy Using a Cervical Approach Under a Pneumomediastinum., Seminars in Thoracic and Cardiovascular Surgery, Vol.S1043, No.19, 121-127, 2018.
There are cases in which one-lung ventilation is difficult due to contralateral lung resection or low lung function. Selective lobar blockade can improve oxygenation compared with one-lung ventilation and secure a good operative field by inducing partial collapse. We report two cases of lung resection involving selective lobar blockade. (Case1) An 80-year-old female had previously undergone right upper and middle lobectomy for multiple lung tumors. Surgery was scheduled to remove a 7‐mm ground glass opacity from the upper left lobe. Oral intubation was performed (inner diameter of intubation tube:8mm). Next, the left upper lobe bronchus was blocked with a7Fr Arndt blocker under bronchoscopy, and partial resection of the left upper lobe was conducted. (Case2) A 75-year-old male had previously undergone right upper lobectomy for pulmonary tuberculosis and had developed right chronic empyema. Surgery was scheduled to remove a 22-mm nodule from the left lingular segment. Oral intubation was performed(inner diameter of intubation tube:8．5mm). Next, the left lingual bronchus was blocked with a7Fr Arndt blocker under bronchoscopy. Left lingular segmentectomy was carried out under thoracoscopic assistance. Intraoperative oxygenation was maintained in both cases, and the release of the block due to hypoxemia was not required in either case.
(キーワード)
肺癌 (lung cancer) / surgery / 麻酔 (anesthesia) / blocker
Takahiro Yoshida, Hiroaki Miyata, Hiroyuki Konno, Hiraku Kumamaru, Akira Tangoku, Yoshihito Furukita, Norimichi Hirahara, Go Wakabayashi, Mitsukazu Gotoh and Masaki Mori : Risk assessment of morbidities after right hemicolectomy based on the National Clinical Database in Japan, Annals of Gastroenterological Surgery, Vol.2, No.3, 220-230, 2018.
(要約)
Nationwide databases are expected to provide critical data to improve medical practice. The present study used such data to develop risk models for clinically important outcomes after right hemicolectomy based on preoperative risk factors. Japan's National Clinical Database (NCD) identified 38 030 cases of right hemicolectomy in the years 2011 and 2012. These were used to analyze correlations between mortality and eight selected clinical outcomes of interest by Pearson's correlation coefficient (). To construct risk models for the eight selected clinical outcomes, 80% of all the examined cases were extracted randomly as a development cohort, and preoperative risk factors for each clinical outcome were identified using a forward stepwise selection method. Morbidities predicted from the risk models were used to find areas under the receiver operator curves among the remaining 20% of the testing cohort. The following clinical outcomes were identified as highly associated with operative mortality: systemic sepsis ( = .360), renal failure ( = .341), unplanned intubation ( = .316) and central nervous system (CNS) occurrences ( = .301). Risk models containing up to 21 preoperative variables were constructed for these eight postoperative clinical outcomes. Predictive values of the eight models were as follows: surgical site infections (0.634), anastomotic leakage (0.656), systemic sepsis (0.816), pneumonia (0.846), unplanned intubation (0.838), renal failure (0.883), CNS occurrences (0.833) and transfusion >5 units (0.846). This study indicated that the NCD-generated risk models for six of the eight selected critical postoperative outcomes had high discrimination among right hemicolectomy patients. These risk models can accurately identify high-risk patients prior to surgery.
Takeshi Nishino, Takahiro Yoshida, Masakazu Goto, Seiya Inoue, Takuya Minato, Satoshi Fujiwara, Yota Yamamoto, Yoshihito Furukita, Yasuhiro Yuasa, Hiromichi Yamai, Hirokazu Takechi, Hiroaki Toba, Hiromitsu Takizawa, Mitsuteru Yoshida, Jun-ichi Seike, Takanori Miyoshi and Akira Tangoku : The effects of the herbal medicine Daikenchuto (TJ-100) after esophageal cancer resection, open-label, randomized controlled trial, Esophagus, Vol.15, No.2, 75-82, 2018.
(要約)
Daikenchuto (TJ-100), a traditional Japanese herbal medicine, is widely used in Japan. Its effects on gastrointestinal motility and microcirculation and its anti-inflammatory effect are known. The purpose of this prospective randomized controlled trial was to investigate the effect of TJ-100 after esophagectomy in esophageal cancer patients. Forty patients for whom subtotal esophageal resection for esophageal cancer was planned at our institute from March 2011 to August 2013 were enrolled and divided into two groups at the point of determination of the operation schedule after informed consent was obtained: a TJ-100 (15 g/day)-treated group (n = 20) and a control group (n = 20). The primary efficacy end-points were maintenance of the nutrition condition and the recovery of gastrointestinal function. The secondary efficacy end-points were the serum C-reactive protein (CRP) level and adrenomedullin level during the postoperative course, the incidence of postoperative complications, and the length of hospital stay after surgery. We examined 39 patients because one patient in the TJ-100 group was judged as having unresectable cancer after surgery. The mean age of the TJ-100 group patients was significantly older than that of the control group patients.The rate of body weight decrease at postoperative day 21 was significantly suppressed in the TJ-100 group (3.6% vs. the control group: 7.0%, p = 0.014), but the serum albumin level was not significantly different between the groups. The recovery of gastrointestinal function regarding flatus, defecation, and oral intake showed no significant between-group differences, but postoperative bowel symptoms tended to be rare in the TJ-100 group. There was no significant between-group difference in the length of hospital stay after surgery. The serum CRP level at postoperative day 3 was 4.9 mg/dl in the TJ-100 group and 6.9 mg/dl in the control group, showing a tendency of a suppressed serum CRP level in the TJ-100 group (p = 0.126). The rate of increase in adrenomedullin tended to be high postoperatively, but there was no significant difference between the two groups. TJ-100 treatment after esophageal cancer resection has the effects of prompting the recovery of gastrointestinal motility and minimizing body weight loss, and it might suppress the excess inflammatory reaction related to surgery.
(キーワード)
Adrenomedullin / Aged / C-Reactive Protein / Defecation / Eating / Esophageal Neoplasms / Esophagectomy / Female / Gastrointestinal Tract / Humans / Length of Stay / Male / Middle Aged / Nutritional Status / Phytotherapy / Plant Extracts / Postoperative Complications / Prospective Studies / Recovery of Function / Serum Albumin / Weight Loss
Yoshimasa Miyagawa, Yosuke Matsushita, Hiromu Suzuki, Masato Komatsu, Tetsuro Yoshimaru, Ryuichiro Kimura, Ayako Yanai, Junko Honda, Akira Tangoku, Mitsunori Sasa, Yasuo Miyoshi and Toyomasa Katagiri : Frequent downregulation of LRRC26 by epigenetic alterations is involved in the malignant progression of triple-negative breast cancer., International Journal of Oncology, 2018.
(要約)
Triple-negative breast cancer (TNBC), defined as breast cancer lacking estrogen- and progesterone‑receptor expression and human epidermal growth factor receptor 2 (HER2) amplification, is a heterogeneous disease. RNA-sequencing analysis of 15 TNBC specimens and The Cancer Genome Atlas-TNBC dataset analysis identified the frequent downregulation of leucine-rich repeat-containing 26 (LRRC26), which negatively regulates nuclear factor-κB (NF-κB) signaling, in TNBC tissues. Quantitative polymerase chain reaction and bisulfite pyrosequencing analyses revealed that LRRC26 was frequently silenced in TNBC tissues and cell lines as a result of promoter methylation. LRRC26 expression was restored by 5-aza-2'-deoxycytidine (5'-aza-dC) treatment in HCC1937 TNBC cells, which lack LRRC26 expression. Notably, small interfering RNA-mediated knockdown of LRRC26 expression significantly enhanced the anchorage-independent growth, invasion and migration of HCC70 cells, whereas ectopic overexpression of LRRC26 in BT20 cells suppressed their invasion and migration. Conversely, neither knockdown nor overexpression of LRRC26 had an effect on cell viability in the absence of tumor necrosis factor-α (TNF-α) stimulation. Meanwhile, overexpression of LRRC26 caused the reduction of TNF-α-mediated NF-κB luciferase reporter activity, whereas depleting LRRC26 expression resulted in the upregulation of TNF-α-mediated NF-κB downstream genes [interleukin-6 (IL-6), IL-8 and C-X-C motif chemokine ligand-1]. Taken together, these findings demonstrate that LRRC26 is frequently downregulated in TNBC due to DNA methylation and that it suppresses the TNF-α-independent anchorage-independent growth, invasion and migration of TNBC cells. Loss of LRRC26 function may be a critical event in the aggressiveness of TNBC cells through a TNF-α/NF-κB-independent mechanism.
Mitsuhiro Tsuboi, Kazuya Kondo, Hiromitsu Takizawa, Naoya Kawakita, Toru Sawada, Hiroaki Toba, Yukikiyo Kawakami, Mitsuteru Yoshida, Hisashi Ishikura, Suguru Kimura and Akira Tangoku : A feasibility study of postoperative adjuvant chemotherapy with fluoropyrimidine S-1 in patients with stage II-IIIA non-small cell lung cancer., The Journal of Medical Investigation : JMI, Vol.65, 90-95, 2018.
(要約)
Adjuvant chemotherapy with uracil tegafur (UFT) improved survival among patients with completely resected stage I lung adenocarcinoma. S-1, an oral dihydropyrimidine dehydrogenase (DPD)-inhibitory 5-fluorouracil, is a more potent DPD inhibitor than UFT;therefore, we hypothesized that postoperative adjuvant chemotherapy with S-1 would be effective for advanced non-small cell lung cancer (NSCLC). We conducted a feasibility study of S-1 as postoperative adjuvant chemotherapy in patients with curatively resected pathological stage bold I back 10 bold I and bold I back 10 bold I back 20 bold I A NSCLC. Adjuvant chemotherapy consisted of 9 courses (4-week administration, 2-week withdrawal) of S-1 at 80-120 mg/body per day. Twenty-four patients with completely resected NSCLC were enrolled in this study from November 2007 through December 2010. The primary endpoint was the rate of completion of the scheduled adjuvant chemotherapy. The secondary endpoints were safety, overall survival, and relapse-free survival. Five patients were censored because of disease recurrence. The planned 9 courses of S-1 were administered to completion in 8 patients. Twelve patients completed more than 70% of the planned courses. Grade 3 adverse reactions, such as elevated total bilirubin (4.2%) and pneumonitis (4.2%), were observed, but there were no Grade 4 adverse reactions. Patients who completed more than 70% of the 9 courses demonstrated better overall survival than those who completed less than 70%. Postoperative administration of S-1 may be possible with few severe adverse events as adjuvant chemotherapy for patients with curatively resected pathological stage bold I back 10 bold I -bold I back 10 bold I back 20 bold I A NSCLC. J. Med. Invest. 65:90-95, February, 2018.
Mitsuhiro Tsuboi, Hiromitsu Takizawa, Mariko Aoyama and Akira Tangoku : Surgical treatment of locally advanced papillary thyroid carcinoma after response to lenvatinib, International Journal of Surgery Case Reports, Vol.41, 89-92, 2017.
(要約)
Differentiated thyroid carcinomas (DTC) have good prognoses after complete resection. Nevertheless, when DTC is associated with an aerodigestive invasion, curative surgery is difficult to perform. However, there is no established neoadjuvant therapy for advanced DTC. A 73-year-old man with thyroid papillary carcinoma was referred to our hospital. A computed tomography examination revealed a tumor in the upper right lobe of the thyroid, and multiple bilateral enlarged lymph nodes in the neck, involving the surrounding structures. The enlarged lymph node at the right upper neck was suspected to have invaded the right internal jugular vein, and the left paratracheal lymph node was suspected to have invaded the cervical esophagus and trachea. The tumor was considered resectable; however, surgery would have been highly invasive. Therefore, we initiated neoadjuvant therapy with lenvatinib. After administration of lenvatinib, the tumor decreased in size by 84.3% and the cervical lymph nodes by 56.0%. The patient underwent a total thyroidectomy, modified neck dissection, a resection of the muscular layer of the esophagus, and a tracheal sleeve resection and reconstruction. The SELECT trial demonstrated that lenvatinib had high response rate with short response time, in patients with radioiodine-refractory DTC. The results suggested that lenvatinib could be effective as neoadjuvant therapy. For an advanced DTC that requires removal through invasive surgery, preoperative lenvatinib treatment might be one of the options for a less invasive surgery.
KH-type splicing regulatory protein (KHSRP) is a multifunctional RNA-binding protein, which is involved in several post-transcriptional aspects of RNA metabolism, including microRNA (miRNA) biogenesis. It affects distinct cell functions in different tissues and can have an impact on various pathological conditions. In the present study, we investigated the oncogenic functions of KHSRP and their underlying mechanisms in the pathogenesis of esophageal squamous cell carcinoma (ESCC). KHSRP expression levels were elevated in ESCC tumors when compared with those in non-tumorous tissues by immunohistochemistry, and cytoplasmic KHSRP overexpression was found to be an independent prognosticator for worse overall survival in a cohort of 104 patients with ESCC. KHSRP knockdown inhibited growth, migration, and invasion of ESCC cells. KHSRP knockdown also inhibited the maturation of cancer-associated miRNAs, such as miR-21, miR-130b, and miR-301, and induced the expression of their target mRNAs, such as BMP6, PDCD4, and TIMP3, resulting in the inhibition of epithelial-to-mesenchymal transition. Our findings uncover a novel oncogenic function of KHSRP in esophageal tumorigenesis and implicate its use as a marker for prognostic evaluation and as a putative therapeutic target in ESCC.
Mariko Aoyama, Hiromitsu Takizawa, Mitsuhiro Tsuboi, Yasushi Nakagawa and Akira Tangoku : A case of metastatic follicular thyroid carcinoma complicated with Graves' disease after total thyroidectomy, Endocrine Journal, Vol.64, No.12, 1143-1147, 2017.
(要約)
Thyroid cancer and Graves' disease may present simultaneously in one patient. The incidence of the development of hyperthyroidism from metastatic differentiated thyroid carcinoma is rare. We herein report a case of metastatic follicular carcinoma complicated with Graves' disease after total thyroidectomy. A 57-year-old woman underwent right hemithyroidectomy for follicular carcinoma. Metastatic lesions appeared in the lungs and skull two years after the first surgery, and remnant thyroidectomy was performed for radioactive iodine-131 (RAI) therapy, during which the TSH receptor antibody (TRAb) was found to be negative. The patient was treated with RAI therapy four times for four years and was receiving levothyroxine suppressive therapy. Although radioiodine uptake was observed in the lesions after the fourth course of RAI therapy, metastatic lesions had progressed. Four years after the second surgery, she had heart palpitations and tremors. Laboratory data revealed hyperthyroidism and positive TRAb. She was diagnosed with Graves' disease and received a fifth course of RAI therapy. 131I scintigraphy after RAI therapy showed strong radioiodine uptake in the metastatic lesions. As a result, the sizes and numbers of metastatic lesions decreased, and thyroid function improved. Metastatic lesions produced thyroid hormone and caused hyperthyroidism. RAI therapy was effective for Graves' disease and thyroid carcinoma.
Naoya Kawakita, Kazuya Kondo, Hiroaki Toba, Akiko Yoneda, Hiromitsu Takizawa and Akira Tangoku : A case of atypical type A thymoma with vascular invasion and lung metastasis, General Thoracic and Cardiovascular Surgery, Vol.66, No.4, 239-242, 2017.
(要約)
We present a case of type A thymoma with invasion of the left brachiocephalic vein and lung metastases. An 84-year-old man underwent extended thymectomy combined with left brachiocephalic vein reconstruction and resection of a lung metastasis. Histological examination showed vascular invasion by the tumor. The lung metastasis had high mitotic activity and slight nuclear enlargement, the so-called "atypical" features, but the main part of the primary tumor did not. However, the intravascular portion of the tumor had "atypical" histological features like the lung metastasis. It seems that "atypical" histological features are related to clinically malignant behavior.
Koichiro Kajiura, Hiromitsu Takizawa, Yuki Morimoto, Kiyoshi Masuda, Mitsuhiro Tsuboi, Reina Kishibuchi, Nuliamina Wusiman, Toru Sawada, Naoya Kawakita, Hiroaki Toba, Mitsuteru Yoshida, Yukikiyo Kawakami, Takuya Naruto, Issei Imoto, Akira Tangoku and Kazuya Kondo : Frequent silencing of RASSF1A by DNA methylation in thymic neuroendocrine tumours, Lung Cancer, Vol.111, 116-123, 2017.
(要約)
Aberrant methylation of promoter CpG islands (CGIs) of tumour suppressor genes is a common epigenetic mechanism underlying cancer pathogenesis. The methylation patterns of thymic tumours have not been studied in detail since such tumours are rare. Herein, we sought to identify genes that could serve as epigenetic targets for thymic neuroendocrine tumour (NET) therapy. Genome-wide screening for aberrantly methylated CGIs was performed in three NET samples, seven thymic carcinoma (TC) samples, and eight type-B3 thymoma samples. The methylation status of thymic epithelial tumours (TETs) samples was validated by pyrosequencing in a larger cohort. The expression status was analysed by quantitative polymerase chain reaction (PCR) and immunohistochemistry. We identified a CGI on a novel gene, RASSF1A, which was strongly hypermethylated in NET, but not in thymic carcinoma or B3 thymoma. RASSF1A was identified as a candidate gene statistically and bibliographically, as it showed frequent CGI hypermethylation in NET by genome-wide screening. Pyrosequencing confirmed significant hypermethylation of a RASSF1A CGI in NET. Low-grade NET tissue was more strongly methylated than high-grade NET. Quantitative PCR and immunohistochemical staining revealed that RASSF1A mRNA and protein expression levels were negatively regulated by DNA methylation. RASSF1A is a tumour suppressor gene epigenetically dysregulated in NET. Aberrant methylation of RASSF1A has been reported in various tumours, but this is the first report of RASSF1A hypermethylation in TETs. RASSF1A may represent an epigenetic therapeutic target in thymic NET.
Masakazu Goto, Takahiro Yoshida, Yota Yamamoto, Yoshihito Furukita, Seiya Inoue, Satoshi Fujiwara, Naoya Kawakita, Takeshi Nishino, Takuya Minato, Yasuhiro Yuasa, Hiromichi Yamai, Hirokazu Takechi, Jun-ichi Seike, Yoshimi Bando and Akira Tangoku : CXCR4 Expression is Associated with Poor Prognosis in Patients with Esophageal Squamous Cell Carcinoma, Annals of Surgical Oncology, Vol.24, No.3, 832-840, 2017.
(要約)
Chemokines and their receptors are known to play important roles in the tumorigenesis of many malignancies. The chemokine CXCL12 and its receptors CXCR4 and CXCR7 were suggested to be involved in cancer invasion and metastasis. The aim of this retrospective study was to evaluate the prognostic impact of the expressions of CXCL12, CXCR4 and CXCR7 in patients with esophageal squamous cell carcinoma (ESCC). We used immunohistochemistry (IHC) and reverse transcriptase-polymerase chain reaction (RT-PCR) to evaluate the expressions of CXCL12, CXCR4, and CXCR7 in ESCC patients' tumor biopsy specimens obtained during preoperative endoscopy or surgery. These results were compared with the patients' clinicopathological parameters and survival. IHC was conducted for 172 patients. High expression of CXCR4 in the cytoplasm and nuclei and that of CXCR7 were associated with poor cause-specific survival (CSS) (P= .002 and .010, respectively). The specimens from 52 of the 172 patients were examined by RT-PCR and quantitative real-time PCR. The expression levels of messenger RNA (mRNA) of CXCR4 and CXCR7 were significantly increased in the tumors compared with normal esophageal mucosae (P < .0001). The expression level of mRNA of CXCR4 was associated with poor recurrence-free survival and CSS (P = .012 and .038, respectively). CXCR4 expression is associated with poor prognosis in patients with ESCC.
Koichiro Kajiura, Kiyoshi Masuda, Takuya Naruto, Kohmoto Tomohiro, Watanabe Miki, Mitsuhiro Tsuboi, Hiromitsu Takizawa, Kazuya Kondo, Akira Tangoku and Issei Imoto : Frequent silencing of the candidate tumor suppressor TRIM58 by promoter methylation in early-stage lung adenocarcinoma, Oncotarget, Vol.8, No.2, 2890-2905, 2017.
(要約)
In this study, we aimed to identify novel drivers that would be epigenetically altered through aberrant methylation in early-stage lung adenocarcinoma (LADC), regardless of the presence or absence of tobacco smoking-induced epigenetic field defects. Through genome-wide screening for aberrantly methylated CpG islands (CGIs) in 12 clinically uniform, stage-I LADC cases affecting six non-smokers and six smokers, we identified candidate tumor-suppressor genes (TSGs) inactivated by hypermethylation. Through systematic expression analyses of those candidates in panels of additional tumor samples and cell lines treated or not treated with 5-aza-deoxycitidine followed by validation analyses of cancer-specific silencing by CGI hypermethylation using a public database, we identified TRIM58 as the most prominent candidate for TSG. TRIM58 was robustly silenced by hypermethylation even in early-stage primary LADC, and the restoration of TRIM58 expression in LADC cell lines inhibited cell growth in vitro and in vivo in anchorage-dependent and -independent manners. Our findings suggest that aberrant inactivation of TRIM58 consequent to CGI hypermethylation might stimulate the early carcinogenesis of LADC regardless of smoking status; furthermore, TRIM58 methylation might be a possible early diagnostic and epigenetic therapeutic target in LADC.
Hiromitsu Takizawa, Kazuya Kondo, Naoya Kawakita, Mitsuhiro Tsuboi, Hiroaki Toba, Koichiro Kajiura, Yukikiyo Kawakami, Shoji Sakiyama, Akira Tangoku, Atsushi Morishita, Yasushi Nakagawa and Toshiyuki Hirose : Autofluorescence for the diagnosis of visceral pleural invasion in non-small-cell lung cancer, European Journal of Cardio-Thoracic Surgery, Vol.53, No.5, 987-992, 2017.
(要約)
This study was conducted to evaluate the accuracy of autofluorescence as a mode of diagnosis for visceral pleural invasion of non-small-cell lung cancer compared with white-light by means of clinical questions to several thoracic surgeons. Eight independent thoracic surgeons evaluated visceral pleural invasion in 25 cases of non-small-cell lung cancer attached to the visceral pleura on lung windows of preoperative computed tomography images. At the first study meeting to evaluate the accuracy of visceral pleural invasion diagnosis using conventional white-light images, the surgeons diagnosed visceral pleural invasion based on information in preoperative computed tomography images, histological types and videos recorded with white-light mode using a thoracoscope. At the second study meeting to evaluate the accuracy of visceral pleural invasion diagnosis using autofluorescence, the same surgeons diagnosed visceral pleural invasion based on information in 2 videos recorded in white-light mode and in autofluorescence mode using the thoracoscope. The overall average sensitivity, specificity and accuracy of visceral pleural invasion diagnosis by white-light versus autofluorescence mode were 64.6% vs 83.3%, 53.9% vs 73.7% and 56.5% vs 76.0%, respectively. The sensitivity, specificity and accuracy of visceral pleural invasion diagnosis was improved through the additional use of the autofluorescence mode compared with the white-light mode alone.
Koichiro Kajiura, Hiromitsu Takizawa, Kazuya Kondo, Hiroaki Toba, Yukikiyo Kawakami and Akira Tangoku : A case of subcutaneous emphysema induced by a portable thoracic drainage system after pneumonectomy, The Journal of the Japanese Association for Chest Surgery, Vol.31, No.5, 610-615, 2017.
Naoya Kawakita, Hiromitsu Takizawa, Koichiro Kajiura and Akira Tangoku : Indocyanine Green Fluorescence Intraoperative Imaging for Hepatic Hydrothorax With a Small Diaphragmatic Defect, Seminars in Thoracic and Cardiovascular Surgery, Vol.28, No.2, 606-608, 2016.
(キーワード)
Aged, 80 and over / Diaphragm / Disease Progression / Fatal Outcome / Fluorescent Dyes / Humans / Hydrothorax / Indocyanine Green / Intraoperative Care / Liver Cirrhosis / Male / Optical Imaging / Pleural Effusion / Predictive Value of Tests / Treatment Outcome
Naoya Kawakita, Hiromitsu Takizawa, Kazuya Kondo, Shoji Sakiyama and Akira Tangoku : Indocyanine Green Fluorescence Navigation Thoracoscopic Metastasectomy for Pulmonary Metastasis of Hepatocellular Carcinoma, Annals of Thoracic and Cardiovascular Surgery, Vol.22, No.6, 367-369, 2016.
(要約)
Indocyanine green can selectively accumulate in primary hepatocellular carcinoma (HCC) and extrahepatic metastases. We report a patient who underwent resection of pulmonary metastasis of HCC using a thoracoscopic near-infrared imaging system and fluorescent navigation surgery. A 66-year-old man with suspicion of pulmonary metastasis of HCC was referred to our hospital. Indocyanine green was injected intravenously at a dose of 0.5 mg/kg body weight, 20 h before thoracoscopic surgery. An endoscopic indocyanine green near-infrared fluorescence imaging system showed clear blue fluorescence, indicating pulmonary metastasis of HCC in a lingular segment. We performed wide wedge resection using the fluorescence image for navigation to confirm the surgical margins. The specimen was histologically confirmed as a pulmonary metastasis of HCC. In conclusion, thoracoscopic indocyanine green near-infrared fluorescence imaging for pulmonary metastases of HCC is useful in identifying tumor locations and ensuring resection margins.
宇山 攻, Shoji Sakiyama, Mitsuteru Yoshida, Koichiro Kenzaki, Hiroaki Toba, Yukikiyo Kawakami, Kazumasa Okumura, Hiromitsu Takizawa, Kazuya Kondo and Akira Tangoku : Lung regeneration by fetal lung tissue implantation in a mouse pulmonary emphysema model, The Journal of Medical Investigation : JMI, Vol.63, No.3-4, 182-186, 2016.
(要約)
The mortality and morbidity of chronic obstructive pulmonary disease are high. However, no radical therapy has been developed to date. The purpose of this study was to evaluate whether fetal mouse lung tissue can grow and differentiate in the emphysematous lung. Fetal lung tissue from green fluorescent protein C57BL/6 mice at 16 days' gestation was used as donor material. Twelve-month-old pallid mice were used as recipients. Donor lungs were cut into small pieces and implanted into the recipient left lung by performing thoracotomy under anesthesia. The recipient mice were sacrificed at day 7, 14, and 28 after implantation and used for histological examination. Well-developed spontaneous pulmonary emphysema was seen in 12-month-old pallid mice. Smooth and continuous connection between implanted fetal lung tissue and recipient lung was recognized. Air space expansion and donor tissue differentiation were observed over time. We could clearly distinguish the border zones between injected tissue and native tissue by the green fluorescence of grafts. Fetal mouse lung fragments survived and differentiated in the emphysematous lung of pallid mice. Implantation of fetal lung tissue in pallid mice might lead to further lung regeneration research from the perspective of respiratory and exercise function. J. Med. Invest. 63: 182-186, August, 2016.
Miyuki Kanematsu, Masami Morimoto, Masako Takahashi, Junko Honda, Yoshimi Bando, Takuya Moriya, Yukiko Tadokoro, Misako Nakagawa, Hirokazu Takechi, Takahiro Yoshida, Hiroaki Toba, Mitsuteru Yoshida, Aiichiro Kajikawa, Akira Tangoku, Issei Imoto and Mitsunori Sasa : Thirty percent of ductal carcinoma in situ of the breast in Japan is extremely low-grade ER(+)/HER2(-) type without comedo necrosis, The Journal of Medical Investigation : JMI, Vol.63, No.3-4, 192-198, 2016.
(要約)
Background Overdiagnosis in mammography (MMG) is a problem. Combination of MMG and ultrasonography for breast cancer screening may increase overdiagnosis. Most cases of overdiagnosis are low-grade ductal carcinoma in situ (LGD), but no reports have focused on them. Materials and methods We immunostained 169 ductal carcinoma in situ (DCIS) cases for ER, PgR, HER2 and Ki67 and classified them into 4 subtypes: ER(+)/HER2(-), ER(+)/HER2(+), ER(-)/HER2(-) and ER(-)/HER2(+). The Ki67 index was used to evaluate the grade of malignancy and examined for correlations with each ER/HER2 subtype and the nuclear grade (NG), with/without comedo necrosis. Results The Ki67 index correlated significantly with NG, both with/without comedo necrosis, and reliably evaluated the grade of malignancy. The index for ER(+)/HER2(-) (n=117, 69.2%) was 7.45±7.10, which was significantly lower than for each of the other types. The index was 5.71±6.94 for ER(+)/HER2(-) without comedo necrosis (n=52, 30.8%), which was significantly lower than with comedo necrosis. This was considered LGD, characterized by absence of microcalcification in MMG and either presence of a solid mass or cystic lesion or absence of hypoechoic areas in ultrasound. Conclusion In Japan, ER(+)/HER2(-) without comedo necrosis accounts for about 30% of DCIS and is LGD. This may be being overdiagnosed. J. Med. Invest. 63: 192-198, August, 2016.
Masami Morimoto, Masako Takahashi, Junko Honda, Takahiro Yoshida, Mitsuteru Yoshida, Hiroaki Toba, Issei Imoto, Akira Tangoku and Mitsunori Sasa : Assay of serum E2 concentration in postmenopausal breast cancer patients using a high-sensitivity RIA method is generally useful., The Journal of Medical Investigation : JMI, Vol.63, No.3-4, 236-240, 2016.
(要約)
Serum E2 levels determined for postmenopausal women by RIA and LC-MS/MS generally correlated well. High-sensitivity RIA is a potentially useful clinical assay, but it overestimated serum E2 in some women. J. Med. Invest. 63: 236-240, August, 2016.
Hiroaki Toba, Shoji Sakiyama, Hiromitsu Takizawa and Akira Tangoku : Safe and successful treatment with afatinib in three postoperative non-small cell lung cancer patients with recurrences following gefitinib/erlotinib-induced hepatotoxicity., The Journal of Medical Investigation : JMI, Vol.63, No.1-2, 149-151, 2016.
(要約)
Afatinib could be a well-tolerated EGFR-TKI that could be chosen for its relatively low hepatotoxicity, which is attributable to its having a different metabolic mechanism compared to other EGFR-TKIs. J. Med. Invest. 63: 149-151, February, 2016.
Hiroshi Kondo, Keiko Miyoshi, Shoji Sakiyama, Akira Tangoku and Takafumi Noma : Differential Regulation of Gene Expression of Alveolar Epithelial Cell Markers in Human Lung Adenocarcinoma-Derived A549 Clones, Stem Cells International, Vol.2015, 165867, 2015.
(要約)
Stem cell therapy appears to be promising for restoring damaged or irreparable lung tissue. However, establishing a simple and reproducible protocol for preparing lung progenitor populations is difficult because the molecular basis for alveolar epithelial cell differentiation is not fully understood. We investigated an in vitro system to analyze the regulatory mechanisms of alveolus-specific gene expression using a human alveolar epithelial type II (ATII) cell line, A549. After cloning A549 subpopulations, each clone was classified into five groups according to cell morphology and marker gene expression. Two clones (B7 and H12) were further analyzed. Under serum-free culture conditions, surfactant protein C (SPC), an ATII marker, was upregulated in both H12 and B7. Aquaporin 5 (AQP5), an ATI marker, was upregulated in H12 and significantly induced in B7. When the RAS/MAPK pathway was inhibited, SPC and thyroid transcription factor-1 (TTF-1) expression levels were enhanced. After treatment with dexamethasone (DEX), 8-bromoadenosine 3'5'-cyclic monophosphate (8-Br-cAMP), 3-isobutyl-1-methylxanthine (IBMX), and keratinocyte growth factor (KGF), surfactant protein B and TTF-1 expression levels were enhanced. We found that A549-derived clones have plasticity in gene expression of alveolar epithelial differentiation markers and could be useful in studying ATII maintenance and differentiation.
Misako Nakagawa, Masami Morimoto, Hirokazu Takechi, Yukiko Tadokoro and Akira Tangoku : Preoperative diagnosis of sentinel lymph node (SLN) metastasis using 3D CT lymphography (CTLG)., Breast Cancer, Vol.23, No.3, 519-524, 2015.
(要約)
Sentinel lymph node biopsy (SLNB) became a standard procedure for patients with early breast cancer, however, an indication of SLN navigation to metastatic disease may lead to misdiagnosis for staging. Preoperative CTLG with a water-soluble iodinated contrast medium visualizes the correct primary SLNs and its afferent lymphatic channels surrounding detailed anatomy, therefore it can predict LN metastasis by visualizing the lymph vessel obstruction or stain defect of the SLN by tumor. The current study presents the value of CTLG for preoperative prediction for SLN status. A total of 228 patients with Tis-T2 breast cancer who did not receive primary chemotherapy were studied. SLN metastasis was diagnosed according to the following staining patterns of SLNs and afferent lymphatic vessels: stain defect of SLN, obstruction, stagnation, dilation, and detour of the lymphatic vessels by tumor occupation. The diagnosis was compared with the pathological results to evaluate the accuracy of prediction for SLN metastasis using CTLG. Twenty-seven of 228 patients had metastatic SLN pathologically. Twenty-five of these were diagnosed as metastatic preoperatively. The accuracy for metastatic diagnosis using CTLG was 89.0 %, sensitivity was 92.6 %, and specificity was 88.6 %. The positive predictive value was 52.1 % and negative predictive value was 98.8 %. CTLG can select the candidate with truly node negative cases in early breast cancer patients, because it predicts lymph node metastasis preoperatively from natural status of the lymphographic image. It also might omit the SLN biopsy itself.
Masami Morimoto, Yoshimi Bando, Misako Nakagawa, Hirokazu Takechi, Takahiro Yoshida, Junko Honda, Yukiko Tadokoro, Takuya Moriya, Mitsunori Sasa and Akira Tangoku : Immunocytochemical results for HER2 and Ki67 in breast cancer touch-smear cell specimens are reliable., Breast Cancer, Vol.23, No.4, 577-582, 2015.
(要約)
HER2 and Ki67 were analyzed in TSC from 36 and 28 patients, respectively. The HER2 expression scores in the TSC and HS groups showed good agreement (kappa value =0.640) and significant correlation (correlation coefficient =0.860, p < 0.001). The Ki67 indexes in the TSC and HS groups also showed significant correlation (correlation coefficient =0.861, p < 0.001).
Masakazu Goda, Osamu Jinnouchi, Tsukasa Takaoka, Koji Abe, Koichi Tamura, Yutaka Nakaya, Yoshihito Furukita, Hirokazu Takechi, Akira Tangoku and Noriaki Takeda : Efficacy of percutaneous endoscopic gastrostomy on unplanned treatment interruption and nutritional status in patients undergoing chemoradiotherapy for advanced head and neck cancer., The Journal of Medical Investigation : JMI, Vol.62, No.3-4, 173-176, 2015.
(要約)
It is suggested that therapeutic PEG placement is useful for preventing unplanned interruption of CRT in patients with advanced head and neck cancer. After severe mucositis and inadequate oral intake have developed during CRT, PEG placement should be considered before the radiation therapy dose of 30 Gy.
Mitsuteru Yoshida, Shoji Sakiyama, Kazuya Kondo and Akira Tangoku : Thoracoscopic pericardial fenestration for effective long-term management of non-tuberculous mycobacterium pericarditis, General Thoracic and Cardiovascular Surgery, Vol.63, No.1, 49-51, 2015.
(要約)
The long-term consequences of non-tuberculous mycobacterium pericarditis with pericardial effusion after fenestration have not been described. We encountered a case of non-tuberculous mycobacterium pericarditis in a 59-year-old woman with an underlying collagenosis. Repeated drainage was required because of rapid reaccumulation of the effusion. To definitively control the effusion, pericardial fenestration was performed by video-assisted thoracoscopic surgery. Chest radiography performed 6 years postoperatively showed no accumulation of pericardial or pleural fluid. The patient required careful follow-up and, to date, the pulmonary non-tuberculous mycobacterium (NTM) infection has been successfully suppressed by continuous antibiotic therapy. Pericardial fenestration with antibiotic therapy was an appropriate treatment for recurrent effusion in this case of NTM pericarditis.
Takahiro Yoshida, Akira Tangoku, Yoshihito Furukita, Takeshi Nishino and Hirokazu Takechi : Long-term survival for advanced esophageal cancer patients with an esophago-bronchial fistula can be achieved by timely multimodality therapy, Esophagus, Vol.12, No.3, 277-285, 2015.
Hisashi Matsuoka, Kazuya Kondo, Hiromitsu Takizawa, Haruhiko Fujino, Etsuko Sakamoto, Junji Uchida, Koh Uyama, Hiroaki Toba, Koichiro Kenzaki, Shoji Sakiyama and Akira Tangoku : Comprehensive evaluation of the response of genes to the administration of the antitumor drug S-1 using a low density array., International Journal of Oncology, Vol.46, No.2, 569-577, 2014.
(要約)
S-1 is a newly developed dihydropyrimidine dehydrogenase inhibitory fluoropyrimidine that exhibits high clinical efficacy against non-small cell lung cancers. To identify genes that may be associated with chemosensitivity to the antitumor drug S-1, we used a low density array representing 93 genes to analyze expression profiles in 4 orthotopically implanted lung cancers derived from human lung cancer cell lines (Lu99, Lu130, LC6 and A549). The tumor growth inhibition (TGI) rates of S-1 in orthotopically implanted tumors of the Lu99, Lu130, LC6 and A549 cell lines were 34.6, 37.5, 32.1 and 3.6%, respectively. The expression of the PRSS3, ABCC4, TXN, SHMT1 and CMPK genes was significantly promoted in the orthotopically implanted SCID mouse model of the 4 lung cancer cell lines by the administration of S-1, while the expression of the LMO7 and FOLH1 genes was significantly suppressed. The expression of the ABCC1, 2 and TST genes was negatively correlated with TGI. The expression of the TK1 and ERCC2 genes was positively correlated with TGI. The results of the present study suggest that the expression of the ABCC1, 2, TST, TK1 and ERCC2 genes is related to resistance to the antitumor drug S-1.
Khalil Abdellah Hamed Ali, Hiroaki Toba, Shoji Sakiyama, Ryo Yamamoto, Hiromitsu Takizawa, Koichiro Kenzaki, Kazuya Kondo and Akira Tangoku : Holter ECG monitoring of sympathovagal fluctuation during bronchoscopy., The Clinical Respiratory Journal, 2014.
(要約)
Heart rate increased significantly after pre-medication compared with that before pre-medication and increased further during bronchoscopy. The coefficient of variation (CVRR ) values after pre-medication and during bronchoscopy were significantly higher than those before pre-medication (P = 0.031 and P = 0.041, respectively). The low frequency (LF) power decreased during bronchoscopy. LF powers obtained after bronchoscopy were significantly lower than those obtained before bronchoscopy (P < 0.041). The high-frequency (HF) power was found to be decreased during bronchoscopy. In particular, HF powers obtained after bronchoscopy were significantly lower than those obtained before bronchoscopy (P < 0.019). Although the LF/HF ratios increased after pre-medication, they decreased temporarily during the bronchoscope insertion.
Mohamed Mokhtar, Yukiko Tadokoro, Misako Nakagawa, Masami Morimoto, Hirokazu Takechi, Kazuya Kondo and Akira Tangoku : Triple assessment of sentinel lymph node metastasis in early breast cancer using preoperative CTLG, intraoperative fluorescence navigation and OSNA., Breast Cancer, 2014.
(要約)
SLN were identified by preoperative CTLG and intraoperative SLNB with fluorescence navigation in all patients, the identification rate was 100 %. SLN metastases were detected as positive by OSNA in 9 patients (18 %), 4 were (++), 4 were (+) and 1 was (+I). SLN metastases were detected as positive by histopathology in 10 patients (20 %). The concordance rate between OSNA and permanent sections was 90 %. The negative predictive value of CTLG was 80 %.
Mohamed Mokhtar, Kazuya Kondo, Hiromitsu Takizawa, Tamaki Otani, Hideki Otsuka, Hitoshi Kubo, Koichiro Kajiura, Yasushi Nakagawa, Yukikiyo Kawakami, Mitsuteru Yoshida, Haruhiko Fujino, Shoji Sakiyama and Akira Tangoku : Non-invasive monitoring of anticancer effects of cisplatin on lung cancer in an orthotopic SCID mouse model using [¹⁸F] FDG PET-CT., Oncology Reports, Vol.31, No.5, 2007-2014, 2014.
(要約)
Positron emission tomography-computed tomography (PET-CT) with [18F] fluorodeoxyglucose (FDG) has recently been applied for evaluating tumor response to anticancer therapy. The aim of the present study was to evaluate the utility of FDG PET-CT in monitoring non-invasively and repeatedly the inhibitory effect of cisplatin (CDDP) on an orthotopic lung cancer model. Validation of in vivo FDG uptake in human lung cancer Ma44-3 cell line in an orthotopic SCID mouse model was carried out. Next, we assessed the use of FDG PET-CT to monitor the response of orthotopic lung cancer to the anticancer effect of CDDP. SCID mice were divided into the CDDP group (7 mg/kg single dose intraperitoneally) and the control group. Tumor volume and maximal standardized uptake value (SUV max) were calculated for all mice. All mice were sacrificed for histopathologic analysis. Validation of FDG PET-CT showed that tumor volume and SUV max were significantly correlated with postmortem tumor length measured in specimens (P=0.023) and (P=0.012), respectively, and there was a significant correlation between SUV max and tumor volume (P=0.048). Response monitoring showed that significant growth inhibition by CDDP in the form of SUV max of the CDDP group was significantly lower than that of the control group on day 8 (P=0.02) and on day 13 (P=0.003). Tumor volume of the CDDP group was significantly lower than that of the control group on day 13 (P=0.03). The present study supports using FDG PET-CT in monitoring tumor progression and therapeutic response of lung cancer in an orthotopic model non‑invasively and repeatedly.
A key challenge in diagnosis and treatment of thymic epithelial tumors (TET) is in improving our understanding of the genetic and epigenetic changes of these relatively rare tumors. Methylation specific PCR (MSP) and immunohistochemistry were applied to 66 TET to profile the methylation status of DNA repair gene O6-methylguanine DNA methyltransferase (MGMT) and its protein expression in TET to clarify the association between MGMT status and clinicopathological features, response to chemotherapy and overall survival. MGMT methylation was significantly more frequent in thymic carcinoma than in thymoma (17/23, 74% versus 13/44, 29%; P<0.001). Loss of expression of MGMT protein was significantly more frequent in thymic carcinoma than in thymoma (20/23, 87% versus 10/44, 23%; P<0.0001). There is a significant correlation between of MGMT methylation and loss of its protein expression (P<0.0003). MGMT methylation and loss of expression were significantly more frequent in advanced thymic epithelial tumors (III/IV) than in early tumors (I/II). MGMT methylation plays a soul role in development of TET, especially in thymic carcinoma. Therefore, translation of our results from basic molecular research to clinical practice may have important implication for considering MGMT methylation as a marker and a target of future therapies in TET.
(キーワード)
Adult / Aged / 発癌 (carcinogenesis) / Carcinoma / DNA Methylation / DNA Modification Methylases / DNA Repair Enzymes / Epigenesis, Genetic / Humans / Male / Middle Aged / Neoplasm Staging / Neoplasms, Glandular and Epithelial / Promoter Regions, Genetic / Thymoma / Thymus Neoplasms / Tumor Suppressor Proteins
Hirokazu Takechi, Kazuaki Mawatari, Nagakatsu Harada, Yutaka Nakaya, Megumi Asakura, Mutsumi Aihara, Hiromitsu Takizawa, Masakazu Goto, Takeshi Nishino, Takuya Minato, Yoshihito Furukita, Yota Yamamoto, Yasuhiro Yuasa, Hiromichi Yamai, Takahiro Yoshida, Jun-ichi Seike and Akira Tangoku : Glutamine protects the small intestinal mucosa in anticancer drug-induced rat enteritis model., The Journal of Medical Investigation : JMI, Vol.61, No.1-2, 59-64, 2014.
(要約)
Supportive therapy during chemotherapy has become essential, but effective preventive therapies to gastrointestinal mucosal injury are few. We investigated the efficacy of glutamine in rat anticancer drug-induced enteritis model. In this study, we used twenty male SD rats. They were divided into control, 5-fluorouracil (5-FU) (orally administered at 20 mg/kg day), 5-FU+glutamine (1000 mg/kg/day) and 5-FU+glutamine+fiber and oligosaccharide (GFO(®)) (1000 mg/kg/day) groups. All groups were sacrificed on day 6 and upper jejunums were excised. The jejunal villous height was measured in specimens. IgA level in jejunal washing solution, and serum diamine oxidase activity were also measured. The jejunal villous height was recognized as shorter in the specimen from 5-FU treated rats compared with 5-FU+glutamine treated rats (p<0.001). Serum diamine oxidase activity in 5-FU+glutamine group were significantly superior to that in 5-FU group (p=0.028). IgA level in jejunal washing solution tended to be higher in 5-FU+glutamine group than that in 5-FU group (p=0.076). On the other hand, serum diamine oxidase activity and IgA level in jejunal washing solution showed no significant difference between 5-FU+GFO and 5-FU treatment group. Our results suggest that glutamine showed protective effects on mucosal injury of small intestine in rat anticancer drug-induced enteritis model.
(キーワード)
glutamine / gastrointestinal toxity / anticancer drug / diamine oxidase / IgA
Khasag Narmisheekh, Shoji Sakiyama, Hiroaki Toba, Mitsuteru Yoshida, Yasushi Nakagawa, Hiromitsu Takizawa, Yukikiyo Kawakami, Koichiro Kenzaki, Ali Hamed Khalil Abdellah, Kazuya Kondo and Akira Tangoku : Monitoring of exhaled carbon monoxide and carbon dioxide during lung cancer operation, European Journal of Cardio-Thoracic Surgery, Vol.45, No.3, 531-536, 2013.
(要約)
Carbon monoxide (CO) is expelled mainly via the lungs, so that exhaled carbon monoxide (Ex-CO) concentration reflects endogenous production. Recent reports have shown that Ex-CO levels are increased in critically ill patients and after anaesthesia and surgery. However, there has been no investigation of the changes in Ex-CO level during a lung operation. We continuously monitored Ex-CO and exhaled carbon dioxide (Ex-CO2) concentrations during surgery for lung cancer. Eighteen lung cancer patients who underwent elective lung cancer lobectomy were enrolled in this study. All patients were endotracheally intubated and ventilated under general anaesthesia. Ex-CO and Ex-CO2 concentrations were separately monitored and recorded continuously using two sets of Carbolyzer® breath analysers (Taiyo Inc., Osaka, Japan). Ex-CO concentration increased rapidly in response to changes in body position from supine to decubitus and was significantly decreased when patients were once again lying back (supine 2). Upon restarting bilateral ventilation, Ex-CO concentration in the operated lung was significantly higher than that in the breathing lung. In the lateral decubitus position, Ex-CO2 concentration showed the same pattern of increase as seen for Ex-CO. In the operated lung, the Ex-CO2 concentrations changed significantly at clamping, declamping and supine 2. In the re-ventilated, operated lung, the Ex-CO2 concentration was significantly lower than in the breathing lung. In the breathing lung, the Ex-CO2 concentration did not exhibit any significant changes over the course of the operation. When breathing was restarted, the Ex-CO level of the target lung was significantly higher than that of the breathing lung. The Ex-CO concentration was also affected by the surgical body position and this change was marked and transient.
Hiroaki Toba, Kazuya Kondo, Yohei Sadohara, Hideki Otsuka, Masami Morimoto, Koichiro Kajiura, Yasushi Nakagawa, Mitsuteru Yoshida, Yukikiyo Kawakami, Hiromitsu Takizawa, Koichiro Kenzaki, Shoji Sakiyama, Yoshimi Bando and Akira Tangoku : 18F-fluorodeoxyglucose positron emission tomography/computed tomography and the relationship between fluorodeoxyglucose uptake and the expression of hypoxia-inducible factor-1, glucose transporter-1 and vascular endothelial growth factor in thymic epithelial tumours., European Journal of Cardio-Thoracic Surgery, Vol.44, No.2, e105-e112, 2013.
(要約)
OBJECTIVES: The objective of this study was to evaluate the usefulness of (18)F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) and the relationships among the expressions of hypoxia-inducible factor-1 (HIF-1), glucose transporter-1 (Glut-1) and vascular endothelial growth factor (VEGF), histological type, other clinical factors and FDG uptake in thymic epithelial tumours. METHODS: Thirty-three patients who underwent FDG-PET/CT before treatment were reviewed. All types of tumours were reclassified into three subgroups: low-risk thymomas (types A, AB and B1), high-risk thymomas (types B2 and B3) and thymic carcinomas. Tumour contour, pattern of FDG uptake, tumour size and maximum standardized uptake value (SUVmax) were obtained. Expressions of HIF-1, Glut-1 and VEGF were analysed immunohistochemically, and these expressions were evaluated using grading scales. RESULTS: FDG uptake was visually recognized in all (100%) tumours. A homogeneous pattern of FDG uptake was increasingly observed in the order of low-risk thymomas to high-risk thymomas to thymic carcinomas (P = 0.016). SUVmax for thymic carcinomas was significantly higher than that for thymomas (P = 0.008). With the optimal cut-off value of SUVmax of 5.6, the sensitivity, specificity and accuracy for diagnosing thymic carcinoma were 0.75, 0.80 and 0.79, respectively. Regarding the mean scoring of HIF-1, Glut-1 and VEGF, increasing trends were observed in the order of low-risk thymomas to high-risk thymomas to thymic carcinomas. Tumour size revealed a significant correlation with SUVmax (r = 0.60, P < 0.001), and the expression of HIF-1 showed a moderate association, but the expression of Glut-1 showed no correlation with SUVmax. Regarding correlations between the expression of the three markers, there were moderate associations between HIF-1 and Glut-1, and HIF-1 and VEGF, and a significant correlation between Glut-1 and VEGF (r = 0.60, P < 0.001). In type B1 thymoma, HIF-1 and Glut-1 were partly expressed in non-neoplastic immature lymphocytes. CONCLUSIONS: FDG-PET/CT should be performed in patients with tumours in the anterior mediastinum because the pattern of FDG uptake and SUVmax are useful in the differential diagnosis of thymic epithelial tumours. Furthermore, the expressions of HIF-1, Glut-1 and VEGF might be associated with malignancy of thymic epithelial tumours. In contrast, FDG uptake might be dependent on tumour size rather than Glut-1 overexpression.
Takeshi Nishino, Yota Yamamoto, Mayumi Ikeda, Masami Morimoto, Yoshihito Furukita, Masakazu Goto, Yoshihito Furukita, Hirokazu Takechi, Junichi Seike, Akira Tangoku and Haruo Fujiwara : [Pathological Complete Response in a Case of Advanced Esophageal Cancer Invading Aorta Treated by Preoperative Chemotherapy with Docetaxel and Cisplatin plus 5-FU]., Japanese Journal of Cancer and Chemotherapy, Vol.40, No.5, 643-646, 2013.
(要約)
The patient was a 64-year-old man, diagnosed as cStage IVa esophageal cancer invading the aorta with lymph node metastasis. He received combination chemotherapy with docetaxel/cisplatin/5-FU(DFP therapy). After one course, CT and endoscopic examination showed remarkable reduction of the primary lesion and lymph node metastasis. We performed subtotal esophagectomy and gastric tube reconstruction by the retroposterior mediastinum route. The pathological specimen evidenced fibrosis and infiltration of inflammatory cells on almost all layers, but showed no viable malignant cells in the middle thoracic esophagus. Therefore, the pathological effect was judged as Grade 3(pCR). This case suggested that DFP combination chemotherapy may prove to be a useful treatment for advanced esophageal cancer with invasion to other organs.
(文献検索サイトへのリンク)
● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 23863591
Hiroaki Toba, Kazuya Kondo, Takanori Miyoshi, Koichiro Kajiura, Mitsuteru Yoshida, Yukikiyo Kawakami, Hiromitsu Takizawa, Koichiro Kenzaki, Shoji Sakiyama and Akira Tangoku : Fluoroscopy-assisted thoracoscopic resection after computed tomography-guided bronchoscopic metallic coil marking for small peripheral pulmonary lesions., European Journal of Cardio-Thoracic Surgery, 2013.
(要約)
OBJECTIVES: To re-evaluate the efficacy of fluoroscopy-assisted thoracoscopic resection after computed tomography (CT)-guided bronchoscopic metallic coil marking (FATS-CM), which was our original method for small peripheral pulmonary lesions. METHODS: Fifty-eight patients with 63 lesions underwent FATS-CM. A metallic coil was installed in the bronchus nearest to the lesion under CT fluoroscopic guidance with ultrathin bronchoscopy. The virtual bronchoscopic navigation (VBN) system was used in 14 cases. Afterwards, we basically performed wide wedge resection (WWR) using a C-arm-shaped roentgenographic fluoroscope during thoracoscopic surgery initially, and then the final procedure was determined by intraoperative histological diagnosis. Moreover, we prospectively treated ground-glass opacity (GGO) lesions of <20 mm diameter according to our treatment protocol from September 2004. RESULTS: We could install coils in the objective bronchi in all cases. The average time required for the marking procedure was 38.9 (15-120) min. Pneumothorax was recognized in 1 (1.7%) case as a complication, but no fatal complications occurred. We could also install coils for each lesion in 4 cases (9 lesions) with multiple lesions. In 14 cases with the VBN system, the examination time and CT number were significantly reduced (P < 0.05 and <0.001, respectively), compared with those of 40 cases without the VBN system. The average interval between the CM and the operation was 5.6 (0-30) days. We never experienced a case of migration preoperatively. Sixty-two (98.4%) lesions were definitively identified, and WWRs were performed using three trocars in 58 (92.1%) cases during thoracoscopic surgery. Lobectomy was initially performed in only 1 case owing to coil migration. Thirty-seven of 40 cases (92.5%) were in line with the treatment protocol. There were no local-regional recurrences in all cases undergoing WWR. CONCLUSIONS: We could prospectively show that our method was suitable to perform WWR with a sufficient margin for small GGO lesions of <20 mm. Moreover, we reconfirmed that the advantages of our method were safety, permitting flexibility in scheduling operations and a high ability to deal with multiple lesions. Additionally, our method became a minimally invasive and mature technique by using a new VBN system.
Seiya Inoue, Hiromitsu Takizawa, Yota Yamamoto and Akira Tangoku : Therapeutic hypothermia for severe cerebral air embolism complicating pleural lavage for empyema., Interactive Cardiovascular and Thoracic Surgery, Vol.17, No.1, 199-201, 2013.
(要約)
Cerebral air embolism during pleural lavage is a rare, but potentially fatal complication. We present a case of severe cerebral air embolism that developed during pleural lavage for empyema and was successfully treated by therapeutic hypothermia. A 77-year old male patient with empyema developed severe cerebral air embolism during pleural lavage via a chest tube. Cranial computed tomography and cranial magnetic resonance imaging showed many small bubbles and widespread infarction in the territory of the right middle cerebral artery. The patient received therapeutic hypothermia maintained at 33°C for 24 h and could leave the hospital without delayed sequelae.
(キーワード)
Aged / Cerebral Angiography / Diffusion Magnetic Resonance Imaging / Embolism, Air / Empyema, Pleural / Humans / Hypothermia, Induced / Intracranial Embolism / Magnetic Resonance Angiography / Male / Therapeutic Irrigation / Tomography, X-Ray Computed / Treatment Outcome
Masami Yoshioka, Daisuke Hinode, Yota Yamamoto, Yoshihito Furukita and Akira Tangoku : Alteration of the oral environment in patients undergoing esophagectomy during the perioperative period, Journal of Applied Oral Science, Vol.21, No.2, 183-189, 2013.
(要約)
During the perioperative period, oral ingestion is changed considerably in esophagectomy patients. The aim of this study was to investigate oral environment modifications in patients undergoing esophageal cancer treatments due to changes in dietary intake and swallowing functions. Thirty patients who underwent operation for removal of esophageal cancer in Tokushima University Hospital were enrolled in this study. It was found that 1) the flow rate of resting saliva decreased significantly at postoperative period by deprived feeding for one week, although it did not recover several days after oral ingestion began, 2) the accumulation of dental plaque and the number of mutans streptococci in saliva decreased significantly after operation, while both increased relatively quick when oral ingestion began, and 3) the swallowing function decreased significantly in the postoperative period. These results suggest that dental professionals should emphasize the importance of oral health care and provide instructions on plaque control to patients during the perioperative period of esophageal cancer treatment.
(キーワード)
Aged / Aged, 80 and over / Deglutition / Dental Plaque / Eating / Esophageal Neoplasms / Esophagectomy / Female / Humans / Male / Middle Aged / Perioperative Period / Saliva / Salivation / Secretory Rate / Statistics, Nonparametric / Streptococcus mutans / Time Factors
Tadaoki Morimoto, Akira Tangoku, Takashi Yamakawa, Masaki Tsuruno and Shigemitsu Takashima : Promotion of quality-controlled mammography alone as a screening modality in Japan., Breast Cancer, Vol.21, No.4, 435-441, 2012.
(要約)
BACKGROUND: The rate of breast cancer screening in Japan has not increased, and it is thought that one of the reasons is the principle that mammography (MMG) and clinical breast examination (CBE) be carried out in combination. Nationwide, there is a shortage of physicians qualified to perform CBE, and in some regions mass-screening is performed by MMG alone out of a mobile MMG bus. In Shikoku, MMG is performed alone as a screening examination in Kochi and Ehime Prefectures. METHODS: A comparative analysis of the data generated by MMG alone in breast cancer screening in the four prefectures of Shikoku during the 2005-2009 period was performed. RESULTS: The overall attendance rates, recall, cancer detection, early-stage cancer detection, and the positive predictive value (PPV) were 16.8-24.5, 6.0-12.8, 0.26-0.37, 63.1-79.7, and 2.8-4.3 %, respectively. Almost no differences were seen between the results for MMG alone and combined MMG/CBE screening. In addition, the cancer detection rates based on the Japan Cancer Society's nationwide data were 0.25 % with combined MMG/CBE screening and 0.21 % with MMG alone, showing almost no difference. CONCLUSIONS: No differences were seen between the results (i.e., recall rate, cancer detection rate, early-stage cancer detection rate, PPV) for MMG alone and MMG/CBE screening in the four prefectures of Shikoku compared with the Japan Cancer Society's nationwide data. In order to improve the mammographic screening rate in Japan, quality-controlled mammography as a stand-alone examination should be promoted, and performed biennially for women aged 50-74 years.
Hideki Otsuka, Yukikiyo Kawakami, Hiromitsu Takizawa, Koichiro Kenzaki, Kazuya Kondo and Akira Tangoku : 18F-fluorodeoxyglucose positron emission tomography/computed tomography is useful in postoperative follow-up of asymptomatic non-small-cell lung cancer patients., Interactive Cardiovascular and Thoracic Surgery, 2012.
(要約)
OBJECTIVESPostoperative follow-up and surveillance after curative resection for non-small-cell lung cancer (NSCLC) patients are generally performed. However, there is no consensus on the best programme at this time. The aim of this study was to evaluate the diagnostic capability of (18)F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) in postoperative NSCLC patients without clinical and radiological evidence of recurrence, as a follow-up and surveillance programme.METHODSBetween January 2005 and April 2010, a total of 101 NSCLC patients underwent potentially curative operations and follow-up FDG-PET/CT was performed in patients without clinical and radiological evidence of recurrence at least once a year in principle. A total of 233 FDG-PET/CT studies were entered and retrospectively reviewed.RESULTSEighteen (18%) asymptomatic patients had recurrent diseases and 22 recurrent sites were confirmed. Of 22 recurrent sites, recurrence was diagnosed by histological examination in 9 (41%) sites and by imaging examination in 13 (59%) sites. FDG-PET/CT correctly diagnosed recurrence in 17 of the 18 (94%) patients and 21 of the 22 (95%) recurrent sites. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 94.4, 97.6, 89.5, 98.8 and 97.0%, respectively. On the other hand, in 3 patients, other diseases were detected and treated appropriately. Post-recurrence therapies were performed in all patients with recurrence, but 4 (22%) patients died of the original diseases. The median post-recurrence survival was 25.2 months, and the 1- and 2-year post-recurrence survival rates were 83.3 and 69.6%, respectively.CONCLUSIONSFDG-PET/CT is a useful tool that has high capability to detect recurrences in asymptomatic NSCLC patients after a potentially curative operation. However, a large-scale multi-institutional randomized control trial may be needed to ascertain the benefit of surveillance with FDG-PET/CT.
Mitsuteru Yoshida, Takanori Miyoshi, Shoji Sakiyama, Kazuya Kondo and Akira Tangoku : Pemphigus with thymoma improved by thymectomy: report of a case, Surgery Today, Vol.43, No.7, 806-808, 2012.
(要約)
A 53-year-old female with pemphigus vulgaris received treatment with prednisolone for 3 years. On chest computed tomography performed at follow-up, an anterior-mediastinal tumor (4 cm × 3 cm) was detected and diagnosed as a thymoma. Although amyosthenia was absent, the patient's anti-acetylcholine-receptor antibody level was high, and she was positive for anti-desmoglein 3 antibodies. She underwent extended thymectomy in the same year, following which both the anti-acetylcholine receptor antibody and the anti-desmoglein 3 antibody levels were normalized. The patient's skin symptoms improved, and the steroid dose was gradually lowered and finally discontinued 4 years postoperatively. Extended thymectomy may be an effective therapy for treating patients with pemphigus.
Akira Tangoku, Yota Yamamoto, Yoshihito Furukita, Masakazu Goto and Masami Morimoto : The New Era of Staging as a Key for an Appropriate Treatment for Esophageal Cancer, Annals of Thoracic and Cardiovascular Surgery, Vol.18, No.3, 190-199, 2012.
(要約)
Fluorodeoxyglucose-positron emission tomography (FDG-PET) and computed tomography (CT) have become the gold standard for staging of esophageal cancer by detecting distant metastases, but metastatic lymph nodes are often difficult to diagnose from the size and standardized uptake value (SUV). If we compare the diagnostic performance of endoscopic ultrasonography (EUS), CT, and FDG-PET in staging of esophageal cancer, EUS is the most sensitive method to identify the detection of regional lymph node metastases, whereas CT and FDG-PET are more specific tests. Combination study with CT, EUS and PETCT cannot make a precise diagnosis after neoadjuvant therapy (NAT). A precise staging might be determined by the fine needle aspiration biopsy (FNAB) under EUS and US screening in the neck and the abdomen even after NAT. Indication of endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) for superficial cancer is sensitive because of difficulty in T1b cancer diagnosis. Detailed examination about vessel invasion and the possibility of residual tumor with dissected specimen will offer an appropriate additional therapy. New strategy like sentinel lymph node (SLN) navigation could supply more information about lymphatic routes and metastatic nodes. SLN navigation with ESD might become a new less invasive strategy for superficial esophageal cancer.
Hiromitsu Takizawa, Kazuya Kondo, Hiroaki Toba, Koichiro Kajiura, Ali Hamed Khalil Abdellah, Shoji Sakiyama and Akira Tangoku : Computed tomography lymphography by transbronchial injection of iopamidol to identify sentinel nodes in preoperative patients with non-small cell lung cancer : A pilot study, Journal of Thoracic and Cardiovascular Surgery, Vol.144, No.1, 94-99, 2012.
(要約)
The objective of the present study was to assess the safety and feasibility of computed tomography lymphography by transbronchial injection of a water-soluble extracellular computed tomography contrast agent. From April 2010 to May 2011, patients with clinical stage I non-small cell lung cancer who were candidates for lobectomy were enrolled in the present study. An ultrathin bronchoscope was inserted to the target bronchus under the guidance of virtual bronchoscopic navigation images. Computed tomography images of the chest were obtained 0.5 and 5 minutes after 2 or 3 mL of iopamidol was injected through a microcatheter. Sentinel nodes were identified when the maximum computed tomography attenuation value of the lymph nodes on the postcontrast computed tomography images increased by 30 Hounsfield units or more compared with the precontrast images. Patients underwent lobectomy with standard lymph node dissection. The ultrathin bronchoscope could access the targeted bronchus, and iopamidol was delivered into the peritumoral area in all 13 patients without any complications. Sentinel nodes were identified in 12 (92.3%) of the 13 patients. The average number of sentinel nodes was 1.5 (range, 1-2). Pathologic examination revealed metastatic lymph nodes in 2 patients. Metastatic nodes were included with the sentinel nodes. Computed tomography lymphography by transbronchial injection of iopamidol was a safe and feasible method to identify the sentinel nodes in patients with clinical stage I non-small cell lung cancer.
Yota Yamamoto, Yamai Hiromichi, Jun-ichi Seike, Takahiro Yoshida, Hirokazu Takechi, Yoshihito Furukita, Koichiro Kajiura, Minato Takuya, Yoshimi Bando and Akira Tangoku : Prognosis of Esophageal Squamous Cell Carcinoma in Patients Positive for Human Epidermal Growth Factor Receptor Family Can Be Improved by Initial Chemotherapy with Docetaxel, Fluorouracil and Cisplatin, Annals of Surgical Oncology, Vol.19, No.3, 757-765, 2012.
(要約)
The human epidermal growth factor receptor (HER) family, Ki-67 and p53 are important biomarkers for several malignancies. However, few studies have examined the role of these in prognosis and therapeutic sensitivity of esophageal squamous cell carcinoma (ESCC). The efficacy of triple-drug combination therapy with docetaxel, fluorouracil and cisplatin has recently been expected for ESCC. Subjects comprised 142 patients with ESCC who underwent operation (OP group, n = 54), neoadjuvant chemotherapy with docetaxel, fluorouracil, and cisplatin (DFP therapy) followed by operation (NAC group, n = 37) or initial systemic DFP therapy (CT group, n = 51) between January 2004 and December 2010. Immunohistochemical expressions of epidermal growth factor receptor (EGFR), HER2, HER3, Ki-67, and p53 were evaluated and compared with prognosis and sensitivity to DFP therapy. Positive correlations existed between EGFR, HER2, and HER3 expressions. In the OP group, EGFR was independently associated with postoperative recurrence in multivariate analysis (P = .036). In the NAC group, EGFR correlated with pathological response to DFP therapy (P = .004). In the CT group, EGFR, HER2, and HER3 correlated with clinical response to DFP therapy and EGFR was independently associated with favorable prognosis in multivariate analysis (P = .022). EGFR represents a predictor of postoperative recurrence and sensitivity to triple-drug combination therapy including a taxane. EGFR-positive patients may show improved prognosis with taxane combination chemotherapy and molecular targeted therapy for HER family members.
Hiroaki Toba, Shoji Sakiyama, Koichiro Kenzaki, Yukikiyo Kawakami, Koh Uyama, Yoshimi Bando and Akira Tangoku : Implantation of fetal rat lung fragments into bleomycin-induced pulmonary fibrosis, Journal of Thoracic and Cardiovascular Surgery, Vol.143, No.6, 1429-1435, 2012.
(要約)
Pulmonary fibrosis is a life-threatening disease that results in progressive respiratory failure. We have suggested the possibility of fetal lung tissue as an option for further investigation into lung regeneration. The objective was to prove whether fetal lung fragments can survive and differentiate in fibrotic lung. Lewis rats were administered bleomycin and used as recipients after 3 or 4 weeks. Day 17 fetal lung tissue from green fluorescent protein Lewis rats was used as donor material. Donor lungs were removed, cut into small pieces, and implanted into the recipients' left lung. The recipients received cyclosporin to prevent immune response to green fluorescent protein and were killed after 1, 2, 4, 8, and 12 weeks and histologically evaluated. Furthermore, the expression of thyroid transcription factor-1 and Clara cell secretory protein in the implanted fetal lung tissue was immunohistologically evaluated. Fibrotic changes were recognized for a long period of time in the recipient lungs. The implanted fetal lung fragments could be clearly distinguished from recipient lungs because of the luminescence of grafts. Fetal lung fragments could survive in the recipient lungs with fibrotic changes. The air spaces of implanted fetal lungs were narrow at 1 and 2 weeks but expanded with the passage of time. The connection between the recipient lung and the implanted fetal lung was recognized, particularly in the peripheral grafts. The expression patterns of thyroid transcription factor-1 and Clara cell secretory protein in implanted lungs resembled those in the process of normal lung morphogenesis. Fetal rat lung fragments could survive and differentiate in bleomycin-induced completely fibrotic lung.
Takuya Minato, Yota Yamamoto, Jun-ichi Seike, Takahiro Yoshida, Hiromichi Yamai, Hirokazu Takechi, Yasuhiro Yuasa, Yoshihito Furukita, Masakazu Goto, Yoshimi Bando and Akira Tangoku : Aldehyde Dehydrogenase 1 Expression is Associated with Poor Prognosis in Patients with Esophageal Squamous Cell Carcinoma., Annals of Surgical Oncology, Vol.20, No.1, 209-217, 2012.
(要約)
BACKGROUND: Aldehyde dehydrogenase 1 (ALDH1) and CD44 act as important biomarkers in several solid tumors. However, few studies have examined the relationships between ALDH1 expression and the prognosis and clinical characteristics of esophageal squamous cell carcinoma (ESCC). METHODS: This study was a retrospective case-control study and included 152 patients with ESCC. A total of 56 patients underwent surgery (OP group), 40 patients received neoadjuvant chemotherapy involving weekly docetaxel plus 5-fluorouracil and low-dose cisplatin (DFP therapy) prior to undergoing surgery (NAC group), and 56 patients received initial systemic DFP therapy (CT group). The ALDH1 and CD44 immunohistochemical expression levels of each tumor were evaluated and compared with the prognosis and clinical characteristics of the ESCC patients. RESULTS: In the OP and NAC groups, multivariate analysis found that ALDH1 was independently associated with postoperative recurrence and prognosis (OP group, P = 0.004 and 0.016, respectively; NAC group, P = 0.026 and 0.014, respectively). In addition, CD44 was found to be associated with postoperative recurrence in the OP group and prognosis in the NAC group (P = 0.024 and 0.047, respectively). Among the ALDH1-negative clinical stage II/III patients, the OP and NAC groups displayed better prognoses than the CT group (P < 0.001). However, among the ALDH1-positive clinical stage II/III patients, the OP and NAC groups displayed poorer prognoses than the CT group (P = 0.049). CONCLUSIONS: ALDH1 was found to be a predictor of postoperative recurrence and prognosis in ESCC, and CD44 might be a predictor of recurrence and prognosis. ALDH1 expression might affect the treatment strategy for ESCC.
Yoshio Kasahara, Masaaki Kawai, Ichiro Tsuji, Eriko Tohno, Takao Yokoe, Minoru Irahara, Akira Tangoku and Noriaki Ohuchi : Harms of screening mammography for breast cancer in Japanese women., Breast Cancer, 2012.
(要約)
BACKGROUND: The US Preventative Services Task Force assesses the efficacy of breast cancer screening by the sum of its benefits and harms, and recommends against routine screening mammography because of its relatively great harms for women aged 40-49 years. Assessment of the efficacy of screening mammography should take into consideration not only its benefits but also its harms, but data regarding those harms are lacking for Japanese women. METHODS: In 2008 we collected screening mammography data from 144,848 participants from five Japanese prefectures by age bracket to assess the harms [false-positive results, performance of unnecessary additional imaging, fine-needle aspiration cytology (FNA), and biopsy and its procedures]. RESULTS: The rate of cancer detected in women aged 40-49 years was 0.28%. The false-positive rate (9.6%) and rates of additional imaging by mammography (5.8%) and ultrasound (7.3%) were higher in women aged 40-49 years than in the other age brackets. The rates of FNA (1.6%) and biopsy (0.7%) were also highest in women aged 40-49 years. However, they seemed to be lower than the rates reported by the Breast Cancer Surveillance Consortium (BCSC) and other studies in the US. CONCLUSIONS: The results, although preliminary, indicate the possibility that the harms of screening mammography for Japanese women are less than those for American women.
Miyuki Kanematsu, Masami Morimoto, Junko Honda, Taeko Nagao, Misako Nakagawa, Masako Takahashi, Akira Tangoku and Mitsunori Sasa : The time since last menstrual period is important as a clinical predictor for non-steroidal aromatase inhibitor-related arthralgia., BMC Cancer, Vol.11, 436, 2011.
(要約)
AIA tends to manifest early after starting AI, but some cases show delayed onset. The incidence was significantly lower in patients with a duration of > 10 years since LMP. When the time since LMP was short, the onset of AIA was significantly earlier after starting AI administration.
Yota Yamamoto, Mayumi Ikeda, Mika Takashima, Takuya Minato, Yoshihito Furukita, Hirokazu Takechi, Junichi Seike and Akira Tangoku : [A case of a patient with stage IVa esophageal cancer surviving over 4 years by combination chemotherapy with docetaxel,5 -FU and cisplatin, without operation]., Japanese Journal of Cancer and Chemotherapy, Vol.38, No.8, 1321-1324, 2011.
(要約)
A male patient in his 50s was found to have lower thoracic advanced esophageal squamous cell carcinoma by upper gastrointestinal endoscopy with the chief complaint of dysphagia in July 2006. CT revealed supraclavicular lymph node metastasis, and he was diagnosed as clinical stage IVa. He underwent two courses of combination chemotherapy with docetaxel, 5-FU and cisplatin(DFP therapy: docetaxel at 25mg/m / / 2 on day 1, 5-FU at 370 mg/m2 on days 1-5, and cisplatin at 7 mg/m2 on days 1-5 were repeated weekly for 4 weeks). The primary tumor disappeared and the lymph node was reduced as observed by upper gastrointestinal endoscopy and CT. After 2 courses of DFP therapy, PET-CT revealed that the primary tumor and lymph node had no new accumulation. Because he refused both operation and chemoradiotherapy, the patient underwent oral chemotherapy. In January 2010, PET-CT and upper gastrointestinal endoscopy revealed that the primary tumor relapsed. DFP therapy was performed and was effective once again. He has survived for over 4 years and 4 months without operation.
Yasuhiro Yuasa, Junichi Seike, Takahiro Yoshida, Hirokazu Takechi, Hiromichi Yamai, Yota Yamamoto, Yoshihito Furukita, Masakazu Goto, Takuya Minato, Takeshi Nishino, Seiya Inoue, Satoshi Fujiwara and Akira Tangoku : Sentinel lymph node biopsy using intraoperative indocyanine green fluorescence imaging navigated with preoperative CT lymphography for superficial esophageal cancer., Annals of Surgical Oncology, Vol.19, No.2, 486-493, 2011.
(要約)
Preoperative CTLG visualized the correct number and site of SLNs in surrounding anatomy during routine computed tomography to evaluate distant metastases. Referring to CTLG, SLNs were identified using IGFI, resulting in successful SLN navigation and saving time and cost. This method appears clinically applicable as a less-invasive method for treating superficial esophageal cancer.
Misako Nakagawa, Yoshimi Bando, Taeko Nagao, Masami Morimoto, Chikako Takai, Takamasa Ohnishi, Junko Honda, Takuya Moriya, Keisuke Izumi, Masako Takahashi, Mitsunori Sasa and Akira Tangoku : Expression of p53, Ki-67, E-cadherin, N-cadherin and TOP2A in triple-negative breast cancer., Anticancer Research, Vol.31, No.6, 2389-2393, 2011.
(要約)
Elucidation of the biological features of triple negative breast cancer (TNBC) is important for deciding treatment strategies. The expression of a number of biomarkers in TNBC was analyzed to elucidate those features. The subjects were 134 TNBC patients. Immunohistochemical staining was employed to analyze for eight biomarkers: cytokeratin 5/6 (CK5/6), epidermal growth factor receptor (EGFR), p53, Ki-67 antigen (Ki-67), E-cadherin, N-cadherin, topoisomerase 2 alpha (TOP2A) and B-cell lymphoma 2 (BCL-2), which were then correlated with the nuclear grade (NG), tumor diameter, and the presence/absence of lymph node metastasis, distant recurrence and lymphatic infiltration. Significantly more high than low NG TNBC exhibited positive p53, Ki-67, E-cadherin and TOP2A. High N-cadherin and TOP2A expression was shown significantly in TNBC with lymphatic infiltration, and N-cadherin was also significantly positively expressed in node metastasis-positive cases. EGFR and CK5/6 were positively expressed in high NG TNBC, but not significantly. Analysis for expression of p53, Ki-67, E-cadherin, N-cadherin and TOP2A is meaningful for deciding treatment strategies for TNBC.
(キーワード)
Antigens, CD / Antigens, Neoplasm / Breast Neoplasms / Cadherins / DNA Topoisomerases, Type II / DNA-Binding Proteins / Female / Humans / Immunohistochemistry / Ki-67 Antigen / Middle Aged / Receptor, erbB-2 / Receptors, Estrogen / Receptors, Progesterone / Tumor Suppressor Protein p53
(文献検索サイトへのリンク)
● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 21737670
Misako Nakagawa, Yoshimi Bando, Taeko Nagao, Chikako Takai, Takamasa Ohnishi, Junko Honda, Takuya Moriya, Keisuke Izumi, Masako Takahashi, Akira Tangoku and Mitsunori Sasa : Among triple-negative breast cancers, HER2(0) breast cancer shows a strong tendency to be basal-like compared with HER2(1+) breast cancer: preliminary results., Breast Cancer, Vol.19, No.1, 54-59, 2011.
(要約)
Diagnosis of triple-negative breast cancer (ER-negative, PgR-negative, HER2-negative; TNBC) is performed by means of immunohistological staining. HER2-negative includes HER2(0) and HER2(1+), based on differences in the staining intensity, but there have been no reports on comparison of these two types in TNBC. Accordingly, this study was designed to investigate the possible differences in the biological characteristics of HER2(0) breast cancer and HER2(1+) breast cancer in TNBC. Tissue specimens from 89 TNBC patients were immunohistochemically stained for CK5/6, EGFR, p53, Ki67, E-cadherin, TOP2A and Bcl-2. The expressions of these markers and the clinicopathological findings were compared between the HER2(0) patient group and the HER2(1+) patient group. When either CK5/6 or EGFR was positive, the specimen was judged to be the basal-like phenotype of breast cancer. The percentages of CK5/6- and/or EGFR-positive specimens in the HER2(0) and HER2(1+) groups were 44.9 and 16.8%, respectively, showing that there was a significantly greater number of basal-like phenotype patients in the HER2(0) group (p < 0.01). The percentage of E-cadherin-positive specimens in the HER2(0) group was 66.6%, which was significantly greater than the 40.0% recorded in the HER2(1+) group (p < 0.05). The respective percentages of TOP2A-positive specimens in the HER2(0) and HER2(1+) groups were 55.0 and 30.0%, and the difference was statistically significant (p < 0.05). In TNBC, HER2(0) breast cancer showed a strong tendency to include more of the basal-like phenotype compared with HER2(1+) breast cancer. The staining results indicated the possibility that HER2(0) breast cancer and HER2(1+) breast cancer have different characteristics.
(キーワード)
Antigens, Neoplasm / Breast Neoplasms / Cadherins / DNA Topoisomerases, Type II / DNA-Binding Proteins / Female / Humans / Ki-67 Antigen / Middle Aged / Receptor, Epidermal Growth Factor / Receptor, erbB-2 / Receptors, Estrogen / Receptors, Progesterone / Tumor Markers, Biological / Tumor Suppressor Protein p53
Abdellah Hamed Khalil Ali, Hiromitsu Takizawa, Kazuya Kondo, Yasushi Nakagawa, Hiroaki Toba, Narmisheekh Khasag, Koichiro Kenzaki, Shoji Sakiyama, Hamdy Ali Mohammadien, Essam Ahmed Mokhtar and Akira Tangoku : Follow-up using fluorescence bronchoscopy for the patients with photodynamic therapy treated early lung cancer., The Journal of Medical Investigation : JMI, Vol.58, No.1-2, 46-55, 2011.
(要約)
To evaluate the accuracy of fluorescence bronchoscopy by precise histological analysis of the photodynamic therapy (PDT) treated lesions.
Junichi Seike, Akira Tangoku, Yasuhiro Yuasa, Hiroshi Okitsu, Yukikiyo Kawakami and Masayuki Sumitomo : The effect of nutritional support on the immune function in the acute postoperative period after esophageal cancer surgery: total parenteral nutrition versus enteral nutrition., --- Enteral nutrition (EN) is now used more frequently than total parenteral nutrition (TPN) for nutritional support after resection for esophageal cancer. But consensus regarding which type of nutrition should be used does not exist. We studied the effect of TPN and EN on patients' nutritional status and immune function in the immediate postoperative period after esophageal cancer resection. ---, The Journal of Medical Investigation : JMI, Vol.58, No.1-2, 75-80, 2011.
(要約)
Enteral nutrition (EN) is now used more frequently than total parenteral nutrition (TPN) for nutritional support after resection for esophageal cancer. But consensus regarding which type of nutrition should be used does not exist. We studied the effect of TPN and EN on patients' nutritional status and immune function in the immediate postoperative period after esophageal cancer resection. We enrolled 30 patients (27 men and 3 women) who underwent subtotal esophagectomy. The patients were randomly assigned to TPN or EN group. Either TPN or EN was begun on postoperative day 1. On postoperative days 1, 3, and 7, three endpoints were measured: albumin, C-reactive protein, and Th1/Th2 balance. All patients completed the study. Anastomotic leaks occurred in 6 patients in the TPN group and 7 patients in the EN group. Albumin, Th1/Th2 balance, and C-reactive protein did not differ between the groups. Th1/Th2 balance was not different regardless of the preoperative treatment or complications. No differences in immune function, nutritional state, or inflammatory response were seen between patients supported with TPN and those supported with EN. The results of our study suggest that perioperative nutritional support can be safely performed either with TPN or EN.
(キーワード)
Aged / C-Reactive Protein / Enteral Nutrition / Esophageal Neoplasms / Female / Humans / Male / Middle Aged / Parenteral Nutrition, Total / Postoperative Care / Postoperative Period / Serum Albumin / Th1 Cells / Th2 Cells
BACKGROUND: It is known that endogenously synthesized protoporphyrin IX (PpIX) following the administration of 5-aminolevulinic acid (5-ALA) is an effective photosensitizer for photodynamic diagnosis (PDD). We tested in vivo and in vitro susceptibility of human lung cancer and mesothelioma cells to photodynamic diagnosis (PDD) using 5-aminolevulinic acid (5-ALA) as a photosensitizer. METHODS: Human lung cancer cell lines A549, Ma44-3, FT821 and human mesothelioma cell lines MSTO-211H, NCI-H290, Y-MESO-14 were incubated with 0.03% 5-ALA for 4h. After incubation, protoporphyrin IX (PpIX) fluorescence was detected using a fluorescence microscope. Pleural carcinosis was induced in severe combined immunodeficiency disease mice using the previous cell lines to test the efficacy of PDD in vivo. The mice were sacrificed 4h after oral administration of 400mg/kg of 5-ALA. We counted the visible tumors under white light then fluorescence light. RESULTS: In vitro, clear red fluorescence was observed in all cell lines. The mean fluorescence intensity was stronger in A549 and FT821 cells than Ma44-3 cells (165.59±26.49, 157.62±18.93 vs. 104.01±17.58). Also, MSTO-211H and NCI-H290 cells had stronger fluorescence intensity than Y-MESO-14 cells (142.51±26.85, 165.16±12.91 vs. 92.31±8.69). In vivo, the tumor detection rate of fluorescence diagnosis was 1.1-4.5 times higher than that of white light. The mean number of metastases detected by the PDD was significantly higher than that of white light for FT821 (p=0.004), Ma44-3 (p=0.006) and Y-MESO-14 cell lines (p=0.005), but not for A549, NCI-H290 and MSTO-211H cell lines. Small lesions were detected by fluorescence diagnosis even though the lesions were invisible macroscopically under white light. CONCLUSION: Our results suggest the possibility of clinical application of fluorescence diagnosis with intrapleural malignant tumors.
Abdellah H. K. Ali, Kazuya Kondo, Toshiaki Namura, Yoshitaka Senba, Hiromitsu Takizawa, Yasushi Nakagawa, Hiroaki Toba, Koichiro Kenzaki, Shoji Sakiyama and Akira Tangoku : Aberrant DNA methylation of some tumor suppressor genes in lung cancers from workers with chromate exposure., Molecular Carcinogenesis, Vol.50, No.2, 89-99, 2010.
(要約)
Our previous studies revealed a variety of genetic changes in lung cancers from chromate-exposed workers (chromate lung cancer). In the present study, we examined epigenetic changes in chromate lung cancers. Nested-methylation-specific PCR was employed in studying the methylation of CpG islands in the APC, MGMT, hMLH1 genes in 36 chromate lung cancers and 25 nonchromate lung cancers. Methylation in chromate lung cancers was detected at 86% for APC, 20% for MGMT, and 28% for hMLH1. Whereas, it occurred at lower frequencies in nonchromate lung cancers, particularly in APC (44%) and hMLH1 (0%) genes. Our previous study showed that methylation of p16 gene in chromate lung cancer and nonchromate lung cancer was 33% and 26%, respectively. The mean methylation index (MI), a reflection of the overall methylation status, was significantly higher in chromate lung cancers than nonchromate lung cancers (0.41 vs. 0.21, P=0.001). Methylation of multiple genes (particularly hMLH1, p16, and APC genes) had experienced more than 15 yr of chromate exposure in chromate lung cancer (MI: <15 yr; 0.19, ≥ 15 yr, 0.42). There is a significant correlation of p16 and hMLH1 methylation with the expressional decrease or loss of the corresponding gene products (P=0.037 and 0.024) respectively, and an inverse correlation between APC and MGMT methylation (P = 0.014). This study provides a novel evidence for the chromium carcinogenesis that chromate lung cancer is linked to the progressive methylation of some tumor suppressor genes, which may be related to genomic instability.
A 69-year-old man and a 53-year-old man with lung cancer of left upper lobe underwent pulmonary resection. A preoperative chest computed tomography (CT) scan showed the left superior and inferior pulmonary veins forming a common trunk. In the former case, the common trunk was misidentified as the superior pulmonary vein. The latter was recognized preoperatively by using 3-dimensional CT, and successfully performed left superior segmentectomy. This variation type is surgically important because of a potential risk of intraoperative bleeding and damage to pulmonary circulation during pulmonary resection.
Hiroaki Toba, Kazuya Kondo, Hideki Otsuka, Hiromitsu Takizawa, Koichiro Kenzaki, Shoji Sakiyama and Akira Tangoku : Diagnosis of the presence of lymph node metastasis and decision of operative indication using fluorodeoxyglucose-positron emission tomography and computed tomography in patients with primary lung cancer., The Journal of Medical Investigation : JMI, Vol.57, No.3-4, 305-313, 2010.
(要約)
PET/CT is superior to CT scan in lymph node staging. However, because the false-positive rate is high in PET-positive lymph nodes measuring less than 1 cm in diameter, we think that clinical background should be considered and other modalities or histological examinations should be undertaken if necessary. J. Med. Invest. 57: 305-313, August, 2010.
Kenji Okazaki, Akira Tangoku, Tadaoki Morimoto, Ryosuke Kotani, Keigo Hattori, Emiko Yasuno, Masatake Akutagawa and Yohsuke Kinouchi : Basic study of a diagnostic modality employing a new electrical impedance tomography (EIT) method for noninvasive measurement in localized tissue, The Journal of Medical Investigation : JMI, Vol.57, No.3,4, 205-218, 2010.
(要約)
The objective of this study is to develop a device for noninvasive local tissue electrical impedance tomography (EIT) using divided electrodes with guard electrodes and to validate its effectiveness using bioequivalent phantoms. For this purpose, we prepared a measurement device and bioequivalent phantoms, measured the electrical characteristics of the phantoms, and validated the method using the phantoms. Monolayer phantoms mimicking the brain and muscle and bilayer phantoms consisting of muscle and brain layers were prepared. The relative differences between the measured electrical conductivities of the monolayer brain and muscle phantoms and the true values determined by the 4-electrode method were both less than 10%. The relative differences between the measured and true values in the bilayer phantoms were less than 20% in both layers. The biological impedance measurement device that we developed was confirmed to be effective for impedance measurement in bilayer phantoms with different electrical impedances. To develop a device for the early diagnosis of breast diseases, the development of a multi-layer phantom and demonstration of the effectiveness of the device for its examination are necessary. If the device that we developed makes impedance measurement in breast tumors possible, it may be used as a new diagnostic modality for breast diseases.
We clinically reviewed 33 surgery patients and 15 non-surgery patients aged 80 years or older with primary lung cancer treated at our hospital. The surgery group consisted of 21 males and 12 females (82.0 +/- 1.9 years old). The surgical procedures were 1 pneumonectomy, 19 lobectomies (1 bronchoplasty), 4 segmentectomies and 9 partial resections. The cancer types were 17 adenocarcinomas, 14 squamous cell carcinomas and 2 others. The stagings were 24 in stage I, 4 in stage II and 5 in stage III. There were no direct surgical deaths within 30 days post operatively. There have been 9 other disease-related deaths to date (27%). The non-surgery group consisted of 9 males and 6 females (81.7 +/- 1.5 years old). Treatment procedures consisted of radiationtherapy in 11, chemotherapy in 2 and best supportive care in 3. The cancer types were 2 adenocarcinomas, 11 squamous cell carcinomas and 2 others. The stagings were 7 in stage I, 4 in stage II and 4 in stage III. There have been 3 other disease-related deaths to date (20%). We must carefully select the therapeutic approach for elderly lung cancer patients, because the other disease-related death rates of both groups were high. The 5-year survival rate of stage I patients in the surgical group was relatively good (60.2%). There were long-term survival (7 5-year survivors) in the surgical group. Since there were some cases of radiation pneumonia in the group receiving radiation therapy, it would be better to perform surgery for elderly patients with lung cancer, especially those with stage I disease. For elderly patients, it is important to consider quality of life as well as the survival rate.
(キーワード)
Age Factors / Aged / Aged, 80 and over / Female / Humans / Lung Neoplasms / Male / Pneumonectomy
(文献検索サイトへのリンク)
● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 20662228
Taeko Nagao, Misako Kira, Masako Takahashi, Junko Honda, Toshiyuki Hirose, Akira Tangoku, Hitoshi Zembutsu, Yusuke Nakamura and Mitsunori Sasa : Serum estradiol should be monitored not only during the peri-menopausal period but also the post-menopausal period at the time of aromatase inhibitor administration., World Journal of Surgical Oncology, Vol.7, 88, 2009.
(要約)
BACKGROUND: Aromatase inhibitor (AI) therapy is being extensively used as postoperative adjuvant therapy in patients with hormone receptor-positive postmenopausal breast cancer. On the other hand, it has been reported that ovarian function was restored when AI was administered to patients who had undergone chemical menopause with chemotherapy or tamoxifen. However, there have been no reports of comprehensive monitoring of estradiol (E2) in breast cancer patients with ordinary menopause who were being administered AI. PATIENTS AND METHODS: Beginning in March 2008, regular monitoring of the serum levels of E2, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) was performed for 66 postmenopausal breast cancer patients who had been started on AI therapy. For this study, we chose anastrozole as the AI. The assays of those hormones were outsourced to a commercial clinical laboratory. RESULTS: In 4 of the 66 patients the serum E2 level was decreased at 3 months but had then increased at 6 months, while in 2 other patients E2 was decreased at both 3 and 6 months but had increased at 9 months. CONCLUSION: The results indicate that, in some breast cancer patients with ordinary menopause, E2 rebounds following AI therapy. In the future, E2 monitoring should be performed for a larger number of patients being administered AI therapy. TRIAL REGISTRATION: Our trial registration number is 19-11-1211.
We herein report a case of thoracic esophageal cancer operated on by mediastinoscope-assisted transhiatal esophagectomy after a right upper lobectomy for primary lung cancer. A 70-year-old male with non-small-cell lung cancer (T4N2M0, cStage III B) underwent chemo-radiation therapy followed by an upper lobectomy of the right lung with mediastinal lymph node dissection. The lung cancer histologically showed complete remission (CR), and no recurrence has been shown. Five years after the operation of lung cancer, esophageal cancer (T3N0M0, cStage II) was endoscopically detected in this patient. Partial remission was obtained after neoadjuvant FP chemotherapy for esophageal cancer. Therefore, mediastinoscope-assisted transhiatal esophagectomy was performed in consideration of a history of a right thoracotomy and of pulmonary dysfunction. Preventive tracheostomy was performed because of recurrent nerve paralysis, but no other severe postoperative complication has developed in this case. Histopathological findings showed a well differentiated squamous cell carcinoma (pT3 (Ad), pN0, M0, pStage II), with involvement at resection margin. He was alive for 11 months after the operation for esophageal cancer, although a local recurrence was observed. There are still many problems remained of the treatment for esophageal cancer patients who had previously undergone a radical operation for lung cancer. However, mediastinoscope-assisted transhiatal esophagectomy may become a procedure for surgical approach if it seems to be difficult to approach the esophageal cancer by thoracotomy again.
Hiroaki Toba, Kazuya Kondo, Koichiro Kenzaki, Takanori Miyoshi, Shoji Sakiyama and Akira Tangoku : Late pulmonary metastases from malignant melanoma of the left planta., General Thoracic and Cardiovascular Surgery, Vol.57, No.10, 558-561, 2009.
(要約)
We report a patient treated for malignant melanoma of the left planta who developed pulmonary metastases after a disease-free interval of 10 years. Metastatectomy was performed after observing progress for 12 months. However, 18 months later, pretracheal and right axillary lymph node metastases occurred. Because pulmonary metastasis from malignant melanoma may occur after 10 years or more, we observe patients carefully. If it does occur, an operation should be considered under limited indications. We should also recognize that recurrence may occur within a short interval after metastatectomy as well.
Takao Tamesa, Norio Iizuka, Naohide Mori, Toshimasa Okada, Norikazu Takemoto, Akira Tangoku and Masaaki Oka : High serum levels of vascular endothelial growth factor after hepatectomy are associated with poor prognosis in hepatocellular carcinoma., Hepato-Gastroenterology, Vol.56, No.93, 1122-1126, 2009.
(要約)
BACKGROUND/AIMS: Vascular endothelial growth factor (VEGF) reportedly affects the metastatic potential of tumors. We investigated in patients whether association exits between perioperative serum VEGF levels and recurrence of hepatocellular carcinoma (HCC). METHODOLOGY: Thirty-two patients who underwent curative resection for HCC were enrolled in this study. Blood samples were obtained at 6 points during the perioperative period: preoperative day and, postoperative days 1, 2, 3, 7 and 14). Serum VEGF levels were measured by enzyme-linked immunosorbent assay. We divided the 32 hepatocellular carcinoma patients into a high VEGF group (preoperative serum level > or = 100 pg/ ml, n = 10) and a low VEGF group (preoperative serum level < 100 pg/ml, n = 22). RESULTS: During a median follow-up period of 27.1 months, the cancer recurred in 20 of the 32 patients. Disease-free survival in the high VEGF group was significantly poorer than that in the low VEGF group (p < 0.05). Serum VEGF levels in the high VEGF group remained significantly higher than those in the low VEGF group after hepatectomy (p < 0.05). Serum VEGF levels in the recurrent group were also significantly higher than those in the non recurrent group at preoperative day, postoperative days 2, 3 and 7 (p < 0.05). CONCLUSIONS: High serum VEGF levels during perioperative period may be a risk factor for intrahepatic recurrence after complete resection for HCC.
(キーワード)
Analysis of Variance / Carcinoma, Hepatocellular / Enzyme-Linked Immunosorbent Assay / Female / Hepatectomy / Humans / Liver Function Tests / Liver Neoplasms / Male / Middle Aged / Neoplasm Recurrence, Local / Predictive Value of Tests / Prognosis / Proportional Hazards Models / Risk Factors / Statistics, Nonparametric / Survival Rate / Tumor Markers, Biological / Vascular Endothelial Growth Factor A
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● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 19760954
Hiromitsu Takizawa, Kazuya Kondo, Hiroaki Toba, Koichiro Kenzaki, Shoji Sakiyama and Akira Tangoku : Fluorescence diagnosis of lymph node metastasis of lung cancer in a mouse model., Oncology Reports, Vol.22, No.1, 17-21, 2009.
(要約)
Fluorescence diagnosis of lymph node metastasis of non-small cell lung cancer has not been reported previously. This study was conducted to evaluate the feasibility of fluorescence detection using 5-aminolevulinic acid and mono-L-aspartyl chlorine e6 for lymph node metastasis in a lung cancer mouse model. Human lung cancer cell line Ma44-3, which forms metastatic lymph nodes in the mediastinum, was injected into the left lungs of 6 severe combined immunodeficiency disease mice. Two weeks after implantation, 2 groups of 3 mice received oral administration of 5-aminolevulinic acid (100 mg/kg) or intraperitoneal administration of mono-L-aspartyl chlorine e6 (5 mg/kg). Both lungs and mediastinal organs were removed en-bloc and illuminated with blue light (405 nm) to evaluate the detectability of lung tumors and metastatic lymph nodes in the mediastinum. These organs were evaluated histopathologically. Clear red fluorescence was observed in the lung tumors of all mice. Metastatic lymph nodes had formed in 5 of 6 mice and were detected by fluorescent detection in all 5 mice even though one of the lymph nodes was invisible macroscopically under white light. In conclusion, fluorescence diagnosis of lymph node metastasis is possible in a mouse model. The successful result with small lymph node metastasis suggests the possibility of clinical application.
We report a case of anaplastic carcinoma of the thyroid administered peroral fluorinated pyrimidine, providing longterm survival during three years. Three years ago, a 70-year-old woman diagnosed with anaplastic carcinoma of the thyroid was admitted for chemoradiation therapy after tumor resection and tracheostomy. The tumor was confirmed to remain on the margin of resected specimens by postoperative histopathology. Combination chemotherapy, including docetaxel, 5-fluorouracil, cisplatin, and radiotherapy, was performed for four weeks. After completion of radiotherapy, CT scan showed residual tumor and lytic clavicular bone findings. But the patient did not desire the same heavy chemotherapy, wishing rather to undergo chemotherapy as an outpatient, if possible. She received chemotherapy with S-1 which was peroral fluorinated pyrimidine for 9 months. In this period, PET-CT showed that accumulation of FDG and lytic clavicular bone findings were continuously confirmed. She was changed to tegafur-uracil(UFT)from S-1, because of myelosuppression. She is alive at this writing in good physical condition. CT shows no tumor growth and no remote metastasis.
M Yoshida, Shoji Sakiyama, Koichiro Kenzaki, Hiroaki Toba, K Uyama, M Takehisa, Kazuya Kondo and Akira Tangoku : Functional evaluation of pallid mice with genetic emphysema., Laboratory Investigation; a Journal of Technical Methods and Pathology, Vol.89, No.7, 760-768, 2009.
(要約)
Studies on pallid mice models of genetic emphysema have conventionally focused on morphological or biochemical evaluations. However, it is important to consider the functional aspects. We evaluated the exercise capacity and respiratory function in male pallid mice and male C57BL/6J mice at 3, 6, 12, and 15 months of age. The functional evaluations were conducted using a treadmill and a pulmonary function analysis device. The morphology of the lungs was analyzed on the basis of mean linear intercept (Lm) values. The body weights of the pallid mice at 12 and 15 months were significantly lower than those of the age-matched C57BL/6J mice. The pallid mice showed deterioration in exercise capacity from 6 months, as indicated by the trends in running distance. At 6, 12, and 15 months, the pallid mice showed significantly higher pulmonary compliance and significantly lower forced expiratory volume in 20 ms (FEV(20 ms))/vital capacity (VC) values in comparison with the corresponding values for the C57BL/6J mice. In the morphological analysis of the pallid mice, emphysema was detected from 12 months, and the mice showed a significantly larger Lm at 12 months. The exercise capacity and lung function in the pallid mice significantly deteriorated from 6 months, at which time no pathological changes in the lung were detected. The deterioration in the exercise capacity and pulmonary function preceded the microscopic morphological changes.Laboratory Investigation advance online publication, 20 April 2009; doi:10.1038/labinvest.2009.34.
Takahiro Yoshida, Takanori Miyoshi, Jun-Ichi Seike, Hiromichi Yamai, Hirokazu Takechi, Yasuhiro Yuasa and Akira Tangoku : Gene expression changes in a chemoresistant model with human esophageal cancer xenografts using cDNA microarray., Anticancer Research, Vol.29, No.4, 1163-1168, 2009.
(要約)
BACKGROUND: 5-Fluorouracil (5-FU) and cisplatin combined chemotherapy (FP) is commonly used for esophageal cancer. Acquired resistance needs to be overcome to improve the chemotherapeutic effect. MATERIALS AND METHODS: The FP-resistant xenograft model using severe combined immunodeficient (SCID) mice was established as an acquired resistance model. RNA was extracted pretreatment, at the onset of the anticancer effect, during the most effective, and regrowth period in the FP administration group and during the mid-progressive period and the far advanced period in the control group. A microarray was applied to explore gene expression changes. RESULTS: The data set containing up-regulated genes in the regrowth period was uploaded into Ingenuity Pathway Analysis. The expression change profiles suggested that activation of not only 5-FU- and cisplatin-specific genes, but also the Phosphoinositide 3-kinase (PI3K)/AKT signal were associated with FP resistance. CONCLUSION: A xenograft model using SCID mice with esophageal cancer cells would monitor gene changes during treatment and regrowth.
(文献検索サイトへのリンク)
● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 19414360
Hiromichi Yamai, Naruhiko Sawada, Takahiro Yoshida, Junnichi Seike, Hiromitsu Takizawa, Koichiro Kenzaki, Takanori Miyoshi, Kazuya Kondo, Yoshimi Bando, Yoshinari Ohnishi and Akira Tangoku : Triterpenes augment the inhibitory effects of anticancer drugs on growth of human esophageal carcinoma cells in vitro and suppress experimental metastasis in vivo., International Journal of Cancer, Vol.125, No.4, 952-960, 2009.
(要約)
The antineoplastic effects of combinations of anticancer drugs (5-fluorouracil, irinotecan and cisplatin) and triterpenes (ursolic acid, betulinic acid, oleanolic acid and a Japanese apricot extract (JAE) containing triterpenes) on esophageal squamous carcinoma cells were examined by the WST-8 (2-(2-methoxy- 4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium, monosodium salt) assay in vitro and by an animal model in vivo. Triterpenes and JAE showed additive and synergistic cytotoxic effects, respectively, on esophageal squamous carcinoma cells (YES-2cells) by combinational use of 5-fluorouracil. JAE and 5-fluorouracil induced cell cycle arrest at G2/M phase and at S phase, respectively, and caused apoptosis in YES-2 cells. A new animal model of esophageal cancer causing tumor colonization of the peritoneal cavity and producing bloody ascites was made by injecting YES-2 cells into the peritoneal cavity of a severe combined immunodeficiency mouse. In this model, 5-fluorouracil inhibited colonization of tumor cells in the peritoneum. The addition of JAE to 5-fluorouracil augmented the suppression of experimental metastasis of the peritoneum. The numbers of peritoneal nodules of more than 2 mm in diameter in mice treated with 5-fluorouracil and JAE were less than those in mice treated with 5-fluorouracil alone or JAE alone. These results suggest that triterpenes, especially JAE, are effective supplements for enhancing the chemotherapeutic effect of 5-fluorouracil on esophageal cancer. (c) 2009 UICC.
Hiroaki Toba, Kazuya Kondo, Hiromitsu Takizawa and Akira Tangoku : Recurrent thymoma with a pleural dissemination invading the intervertebral foramen., European Journal of Cardio-Thoracic Surgery, Vol.35, No.5, 917-919, 2009.
(要約)
We report a rare case of recurrent thymoma with pleural dissemination invading the intervertebral foramen. A woman with Masaoka's stage IVa thymoma with myasthenia gravis (MG) underwent macroscopically complete resection. After 45 months, she developed back pain. Computed tomography (CT) of the chest demonstrated a mass in the right thoracic cavity invading the intervertebral foramen between thoracic vertebrae 10 and 11. She underwent complete resection of the tumor and postoperative radiotherapy. The resected specimen was histologically diagnosed as a pleural dissemination from thymoma. There has been no local recurrence.
We experienced 3 resected cases of pleomorphic carcinoma of the lung. Each cases were 74-year-old man (case 1), 74-year-old woman (case 2) and 69-year-old man (case 3). Two patients (case 1 and 2) were histologically diagnosed as pleomorphic carcinoma composed of spindle cell carcinoma with giant cell carcinoma. One patient (case 3) was similarly diagnosed as pleomorphic carcinoma composed of spindle cell carcinoma with adenocarcinoma and squamous cell carcinoma. Although lymph nodes metastasis were not recognized in all patients, invasion to vessels were recognized in 2 patients (case 1 and 3). In one patient (case 1), recurrence was recognized at contralateral side 1 month after surgery and he died of other disease 2 months after surgery. The other 2 patients were alive without recurrence 24 and 5 months after surgery. Recently it is reported that recurrence is recognized at early phase after surgery and prognosis is poor in a case with vessel invasions in spite of pathological NO state. Since one patient (case 3) had nonmetastatic lymph nodes with vessel invasions, careful observation is considered to be necessary.
(キーワード)
Aged / Aged, 80 and over / Carcinoma / Diagnostic Imaging / Fatal Outcome / Female / Humans / Lung Neoplasms / Male / Neoplasm Staging / Treatment Outcome
(文献検索サイトへのリンク)
● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 19280950
Tadaoki Morimoto, Taeko Nagao, Kenji Okazaki, Misako Kira, Yasushi Nakagawa and Akira Tangoku : Current status of breast cancer screening in the world., Breast Cancer, Vol.16, No.1, 2-9, 2008.
(要約)
The mortality associated with breast cancer is decreasing in Europe and the United States. There are various reasons for these trends, including an increase in detection of early-stage breast cancers due to increased use of mammographic screening and the establishment of standardized systemic treatments based on evidence-based medicine. However, in Japanese women, both the morbidity and the mortality of breast cancer are increasing. In this manuscript, we describe the current status of mammographic screening in Europe and the United States, and the status of breast cancer screening in Japan. Quality control systems are also introduced, and the need for practical measures, such as implementation of quality control systems aimed at improving the cancer screening rate (with a target of 50%) and population-based screening (organized screening), based on the Cancer Control Act, is described. Current countermeasures for dense breasts in women in their 40s, both overseas and in Japan, are also described, together with discussions of the diagnostic capability of digital mammography, the usefulness of screening combined with computer-aided diagnosis, and the current status of screening using MRI in Europe and the United States.
(キーワード)
Breast Neoplasms / 画像診断 (diagnostic imaging) / Female / Humans / Image Interpretation, Computer-Assisted / Mass Screening / Quality Control
In our department, there were 482 thoracic surgeries for primary lung cancer between 1994 and 2007. We clinically reviewed cases that underwent tracheoplasty or bronchoplasty (n = 22, 4.6%). The patients consisted of 21 males and 1 female (66.5 +/- 12.0 years-old). All patients were smokers. The tissue forms were 19 squamous cell carcinomas, 2 adenocarcinomas, 1 large cell carcinoma, 1 adenoid cystic carcinoma and 1 carcinoid, including 2 multiple carcinomas. Sleeve resections involved the trachea in 1, upper lobes in 13, lower lobes in 3, upper-middle lobes in 2 and intermediate bronchus in 1. Wedge resections were performed in the upper lobes in 2. Fourteen reconstructions were performed. We ordinarily sutured the trachea and bronchus in any case, using a single outside knot. There was no leakage at the anastomosis. There were 2 hospital deaths. There were 4 cancer deaths, including 2 local recurrences. There were 4 patients demonstrating stenosis post operatively. There were 3 stenoses among 4 preoperative radiation therapies. We considered that radiation therapy disturbed the repair of the anastomosis. There were 8 pneumonia patients who developed post operatively. There were 2 operative hospital deaths among 3 angio-bronchoplasties without coverage. Recently, we have routinely covered the anastomosis at the reconstruction site and have not experienced any major complications.
BACKGROUND: Thymoma is an uncommon neoplasm derived from epithelial cells of the thymus. Few studies have addressed the genetic alterations that occur in the tumourigenesis of thymoma. METHODS: We examined aberrant DNA methylation of DAP-K, p-16, MGMT and HPP1 genes in 26 thymomas and 6 thymic carcinoma to clarify the association between aberrant DNA methylation and clinicopathological features. RESULTS: Fifteen (47%) of 32 thymic epithelial tumours showed aberrant methylation. Aberrant methylation was more frequent in thymic carcinoma (86%) than in thymoma (29%). Moreover, the frequency of tumours with methylation of multiple genes in thymic carcinoma was higher than in thymoma (60% vs 20%). In thymoma, the frequency of tumour methylation, including the type A tumour component (28%), was lower than that of tumours with type B tumour component (42%). MGMT methylation was detected in 23% of thymoma and in 83% of thymic carcinoma. The frequency of methylation of the MGMT gene in both tumours was high compared with the other 3 genes. CONCLUSIONS: Aberrant DNA methylation was more frequent in thymic carcinoma than in thymoma, and the frequency of DNA methylation in thymic epithelial tumours is roughly parallel to their malignant behaviour.
Toshiyuki Hirose, Junko Honda, Yoshimi Bando, Mitsunori Sasa, Yukiko Hirose, Taeko Nagao and Akira Tangoku : A case of matrix-producing carcinoma of the breast., World Journal of Surgical Oncology, Vol.6, 60, 2008.
(要約)
BACKGROUND: Matrix-producing carcinoma (MPC) of the breast is one variant type of metaplastic carcinoma. The cellular origin of MPC remains unclear. It has been suggested the tumor cells in MPC have the combined characteristics of both epithelial cells and mesenchymal cells. Several reports suggested that the tumor cells in MPC might originate from the myoepithelial cells, but others suggested the origin was basal-like cells. CASE PRESENTATION: The patient was a 42-year-old Japanese female. A tumor of about 2 cm in diameter was noted in the right breast. CT revealed the circumference of the tumor to have a ring-like structure, and fine needle aspiration cytology indicated suspicion for malignancy. Breast-conserving surgery was performed. Histopathological studies showed carcinoma cells, having cuboidal to oval-shaped nucleus, were proliferating in cord-like and sheet-like structures in the periphery. In the central areas of the tumor, myxoedematous area was observed with cartilaginous matrix and necrosis. The diagnosis was a matrix-producing carcinoma. Immunohistochemical findings showed the tumor cells had the characteristics of both epithelial cells and mesenchymal cells, while being negative for estrogen receptor, progesterone receptor, Her2, myoepithelial cell markers and basal cell markers. CONCLUSION: The findings for our present patient and many of the other MPC patients reported in the published literature indicate that this breast cancer has the properties of both epithelial cells and mesenchymal cells. In addition, there is a possibility that matrix-producing tumor cells of our present patient may have a feature of undifferentiated cells.
A 64-year-old woman with advanced esophageal cancer underwent chemotherapy with docetaxel/5-FU/CDDP (DFP). Adverse reactions were severe nausea and general fatigue, so the patient decided to discontinue DFP therapy. The treatment was changed to S-1/docetaxel. Adverse reactions were not so severe, so she could receive 1 course of the medication completely. After the treatment, the primary lesion showed a partial response, so we performed surgery. In the resected specimen, no malignant cell could be seen microscopically. Though the advanced esophageal cancer was regarded as a systemic disease, the appropriate combination of chemotherapy and surgery proved effective.
In recent years thoracotomy by "clamshell incision" has frequently been chosen for heart-lung transplantation, bilateral lung tumors and mediastinal tumor merging into lung tumor because this approach provides very good visibility to access the whole bilateral lung including the lower lobe and mediastinal organs. In our hospital, 4 patients underwent bilateral thoracotomy by clamshell incision for pulmonary metastasectomy between 2001 and 2005. All cases had bilateral pulmonary metastases, and multiple wedge resection was performed. All lesions that were planned for resection on preoperative computed tomography (CT) could be resected. Regarding the surgical approach to bilateral pulmonary metastases that did not need lobectomy, clamshell incision is one of the useful approaches that can allow wedge resection anywhere in the whole lung. In cases that are expected multiple procedures, bilateral thoracotomy by clamshell incision is recommended because it allows another route for thoracotomy at reoperation.
Junko Honda, Mitsunori Sasa, Takuya Moriya, Yoshimi Bando, Toshiyuki Hirose, Masako Takahashi, Taeko Nagao and Akira Tangoku : Thymidine phosphorylase and dihydropyrimidine dehydrogenase are predictive factors of therapeutic efficacy of capecitabine monotherapy for breast cancer-preliminary results., The Journal of Medical Investigation : JMI, Vol.55, No.1-2, 54-60, 2008.
(要約)
Capecitabine monotherapy was administered for 25 patients with advanced or recurrent breast cancer, and the clinical therapeutic efficacy and its relationship to expression of 5-fluorouracil-related enzymes (i. e., thymidine phosphorylase (TP), thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD)) were investigated. The expressions of TP, TS and DPD were determined by immunohistochemical staining techniques and rated using a scoring system of 1~4. The expression score for TP/DPD showed a statistically significant correlation with the clinical response, whereas the expression score for TP/TS also showed a correlation but it was not statistically significant. The number of patients was small, but the results revealed the potential of application of the TP/DPD expression score as a factor for predicting the efficacy of the drug in individual patients.
Sixteen cases of mediastinal lymphoma in our hospital were reviewed clinically. There were 7 men and 9 women, whose mean age is 35 years old. The histological types were non-Hodgkins' disease in 12 (B-cell type in 6 and T-cell type in 6), Hodgkins' disease in 2, mucosa-associated lymphoid tissue (MALT) lymphoma in 2. All cases except 1 in which percutaneous needle biopsy was performed were diagnosed histologically. Even small specimens by percutaneous needle biopsy can be helpful in diagnosing histological type and subtype with immunohistlogy, recommending percutaneous needle biopsy as an mitial step for diagnosis. When histological diagnosis can not be made by needle biopsy, open biopsy should be done.
Hiromitsu Takizawa, Kazuya Kondo, Hisashi Matsuoka, Koh Uyama, Hiroaki Toba, Koichiro Kenzaki, Shoji Sakiyama, Akira Tangoku, Kazumasa Miura, Kiyoshi Yoshizawa and Junji Morita : Effect of mediastinal lymph nodes sampling in patients with clinical stage I non-small cell lung cancer, The Journal of Medical Investigation : JMI, Vol.55, No.1,2, 37-43, 2008.
(要約)
Systematic nodal dissection has been recommended for patients with resectable non-small cell lung cancer because of its staging accuracy. However, in patients with clinical stage I non-small cell lung cancer whether systematic nodal dissection provides more benefits than mediastinal lymph node sampling or not is controversial. In this retrospective study, we evaluated the effect of mediastinal lymph node sampling in patients with clinical stage I NSCLC. One hundred and nineteen consecutive patients with clinical stage I NSCLC, who underwent curative operation between January 1994 and December 2000, were retrospectively reviewed (dissection group = 58: sampling group= 61). Systematic nodal dissection was defined as complete removal of mediastinal lymph node, and mediastinal lymph node sampling was defined as removal of lymph node levels 3, 4, and 7 for right-sided tumors and levels 5, 6, and 7 for left-sided tumors. The total number of removed mediastinal lymph nodes in patients who underwent systematic nodal dissection was 22.1 +/- 9.7, which was significantly higher than that in patients who underwent mediastinal lymph node sampling of 11.4 +/- 7.0 (p < 0.001). Postoperatively N2 disease was detected in 8 patients (13.8%) in the dissection group and 7 (11.5%) in the sampling group. After the median follow up of 79 months, the cancer specific survival rate at 5 year was 78.0% in the dissection group and 76.2% in the sampling group (p = 0.60). Mediastinal lymph node sampling showed the similar effect to systematic nodal dissection in patients with clinical stage I non-small cell lung cancer.
Aoi Matsuoka, Masako Minato, Masafumi Harada, Hitoshi Kubo, Yoshikatsu Bandou, Akira Tangoku, Kiichirou Nakano and Hiromu Nishitani : Comparison of 3.0-and 1.5-tesla diffusion-weighted imaging in the visibility of breast cancer., Radiation Medicine, Vol.26, No.1, 15-20, 2008.
(要約)
PURPOSE: The aim of this study was to compare diffusion-weighted imaging (DWI) at 3.0 T and 1.5 T by evaluating the apparent diffusion coefficient (ADC) value and visibility of breast cancer in the same patients. MATERIALS AND METHODS: A total of 13 patients (16 lesions) with breast cancer underwent DWI at 3.0 T and 1.5 T. Tumors were classified into two groups based on the lesion size. The ADC values were measured, and visibility of the tumors was scored blindly. RESULTS: No significant difference was found for ADC values between 3.0 T and 1.5 T in either group (P > 0.05). All of the large lesions were visible clearly at both magnetic field strengths, and image scores were not different (P > 0.05). In contrast, small lesions were more clearly visible and had better image scores at 3.0 T than at 1.5 T (P < 0.001). CONCLUSION: Small cancers were more clearly visible on DWI at 3.0 T than 1.5 T.
(キーワード)
Breast Neoplasms / Diffusion Magnetic Resonance Imaging / Female / Humans / Image Interpretation, Computer-Assisted
Kazuya Kondo, Takanori Miyoshi, Haruhiko Fujino, Hiromitsu Takizawa, Satoshi Imai, Naoki Kobayashi, Koichiro Kenzaki, Shoji Sakiyama and Akira Tangoku : Photodynamic therapy using a second generation photosensitizer, Talaporfin, Photodiagnosis and Photodynamic Therapy, Vol.4, No.4, 269-274, 2007.
(要約)
Background: Photodynamic therapy (PDT) using Talaporfin is an attractive treatment for centraltype early lung cancer. It was noted that some patients had altered levels of arterial oxygen saturation as indicated by pulse oximeter (SpO2) and arterial oxygen saturation levels in blood gas analysis (SaO2) during PDT. The present experiments were designed to provide an explanation for these findings. Methods: The influence of Talaporfin on SpO2 using in vitro and in vivo experiments, and clinically, was examined. Results: Our in vitro and in vivo experiments showed a linear relationship between Talaporfin concentration in the plasma and the SpO2 level (R = 0.9957 and 0.9837). The apparent SpO2 level decreased according to the increase of Talaporfin concentration in the plasma. In two patients with PDT, SpO2 levels at 4 6 h and 24 h after Talaporfin administration were 93% and 97%, respectively. Conclusions: Talaporfin raised blood absorbance at 660nm with a pulse oximeter. It appeared that the presence of the drug falsely decreased the level of SpO2 since SpO2 did not actually change.
An 80-year-old woman with advanced cervical esophageal cancer underwent chemoradiotherapy with docetaxel/5-FU/CDDP (DFP). The tumor reduced in size after the treatment,but severe pancytopenia and scar stenosis of cervical esophagus appeared. In consideration of her age,the treatment was changed to the administration of UFT alone on an outpatient basis. Ten months after the medication, a follow-up CT scan showed multiple lung metastases and mediastinal lymph node metastases. The patient was treated with DFP therapy again, and all tumors reduced in size, but severe general fatigue and pancytopenia appeared during this therapy. Given the difficulty of continuing this therapy, the treatment was changed to UFT alone on an outpatient basis. The followup CT scan showed a reduction in the size of all tumors even 8 months after discharge. UFT alone appears to be safe and effective as maintenance therapy after DFP therapy, especially for elderly patients.
(キーワード)
Aged, 80 and over / Ambulatory Care / Antineoplastic Combined Chemotherapy Protocols / Cisplatin / Combined Modality Therapy / Drug Administration Schedule / Drug Combinations / Esophageal Neoplasms / Female / Fluorouracil / Humans / Lung Neoplasms / Lymph Nodes / Lymphatic Metastasis / Quality of Health Care / Taxoids / Tegafur / Uracil
(文献検索サイトへのリンク)
● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 17687211
Yukiko Hirose, Mitsunori Sasa, Yoshimi Bando, Toshiyuki Hirose, Tadaoki Morimoto, Yasushi Kurokawa, Taeko Nagao and Akira Tangoku : Bilateral male breast cancer with male potential hypogonadism., World Journal of Surgical Oncology, Vol.5, 60, 2007.
(要約)
BACKGROUND: Male breast cancer is a comparatively rare disease, and simultaneous bilateral male breast cancer is considered to be an extremely rare event. Risk factors are said to be genetic factors and hormonal abnormalities due to obesity or testicular diseases. CASE PRESENTATION: The patient was a 47-year-old Japanese male. His family had no history of female breast cancer. This patient also had hypospadias and hormonal examination indicated the presence of primary testicular potential hypogonadism, and these hormonal abnormalities seemed to be present since childhood or the fetal period. The bilateral breast cancer developed in this man at a comparatively young age, and histopathological studies of multiple sections showed that there was almost no normal epithelial cell in the ducts, while the ducts were almost completely filled with breast cancer cells. CONCLUSION: It is thought that male breast cancer is caused by an imbalance between estrogen and testosterone. We cannot rule out the possibility that the breast cancer developed due to the effect of the slight elevation of estrogen over a long period of time, but the actual causative factors in this patient were unable to be definitively identified. In the future, we hope to further elucidate the causes of male breast cancer.
Masatsugu Takehisa, Mitsunori Sasa, Yoshimi Bando, Toshiyuki Hirose, Tadaoki Morimoto, Taeko Nagao and Akira Tangoku : Chromosomal aneusomy (chr 1, 11, 17) detected by fluorescence in situ hybridization may be a prognostic factor in breast cancer., Anticancer Research, Vol.27, No.2, 1073-1078, 2007.
(要約)
The relationship between clinicopathological findings and the long-term prognosis was investigated in 42 breast cancer patients in whom aneusomy was detected for chromosomes 1, 11 and 17. The frequencies of aneusomy of those chromosomes were 78.6%, 47.5% and 52.5%, respectively, and more than 90% of anomalies consisted of polysomy. The relationship between aneusomy and the clinicopathological findings showed a statistical correlation with a high histological grade in the case of polysomy of chromosome 17 compared with disomy, indicating a tendency for a high incidence of lymph node metastasis. Analysis of the survival data revealed that the prognosis was poor when there was polysomy of chromosomes 1 or 11. These results indicate the possibility that aneusomy of chromosomes 1, 11 and 17 can serve as prognostic factors of poor outcome in breast cancer patients.
Akira Tangoku, Junichi Seike, Kiichiro Nakano, Taeko Nagao, Junko Honda, Takahiro Yoshida, Hiromichi Yamai, Hisashi Matsuoka, Kou Uyama, Masakazu Goto, Takanori Miyoshi and Tadaoki Morimoto : Current status of sentinel lymph node navigation surgery in breast and gastrointestinal tract., The Journal of Medical Investigation : JMI, Vol.54, No.1-2, 1-18, 2007.
(要約)
Sentinel lymph node biopsy (SLNB) has been developed as a new diagnostic and therapeutic modality in melanoma and breast cancer surgery. The purpose of the SLNB include preventing the operative morbidity and improving the pathologic stage by focusing on fewer lymph nodes using immunocytochemic and molecular technology has almost achieved in breast cancer surgery. The prognostic meaning of immunocytochemically detected micrometastases is also evaluating in the SLN and bone marrow aspirates of women with early-stage breast cancer. SLNB using available techniques have suggested that the lymphatic drainage of the gastrointestinal tract is much more complicated than other sites, skip metastasis being rather frequent because of an aberrant lymphatic drainage outside of the basin exist.At the moment, the available data does not justify reduced extent of lymphadenectomy, but provides strong evidence for an improvement in tumor staging on the basis of SLNB. Two large scale prospective multi-center trials concerning feasibility of gamma-probe and dye detection for gastric cancer are ongoing in Japan.Recent studies have shown favorable results for identification of SLN in esophageal cancer. CT lymphography with endoscopic mucosal injection of iopamidol was applicable for SLN navigation of superficial esophageal cancer. The aim of surgical treatment is complete resection of the tumor-infiltrated organ including the regional lymph nodes. Accurate detection of SLN can achieve a selection of a more sophisticated tailor made approach. The patient can make a individualized choice from a broader spectrum of therapeutic options including endoscopic, laparoscopic or laparoscopy-assisted surgery, modified radical surgery, and typical radical surgery with lymph node dissection. Ultrastaging by detecting micrometastasis at the molecular level and the choice of an adequate treatment improve the postoperative quality of life and survival. However these issues require further investigation.
Mitsuteru Yoshida, Kazuya Kondo, Hiroaki Toba, Koichiro Kenzaki, Shoji Sakiyama and Akira Tangoku : Two cases of bronchogenic cyst with severe adhesion to the trachea, The Journal of Medical Investigation : JMI, Vol.54, No.1-2, 187-190, 2007.
(要約)
We experienced two bronchogenic cysts with severe adhesion to the trachea. Both cysts were located on the right side of the trachea. The surgical procedure was changed to thoracotomy from thoracoscopic surgery due to strong adhesion to the trachea. In case 1, sharp separation of the cystic wall from the trachea led to tracheal wall damage. In case 2, the cystic wall except a portion which was adhered to the trachea was resected. The inner side of the residual cystic wall underwent dull curettage to remove the epithelial component. There were no postoperative complications in either case.
Takanori Miyoshi, Kazuya Kondo, Hiroaki Toba, Mitsuteru Yoshida, Haruhiko Fujino, Koichiro Kenzaki, Shoji Sakiyama, Masatsugu Takehisa and Akira Tangoku : Predictive Value of Thymidylate Synthase and Dihydropyrimidine Dehydrogenase Expression in Tumor Tissue, Regarding the Efficacy of Postoperatively Administered UFT(Tegafur+Uracil) in Patients with Non-small Cell Lung Cancer, Anticancer Research, Vol.27, No.4C, 2641-2648, 2007.
(要約)
UFT (tegafur + uracil) has been reported to be effective as an adjuvant in postoperative chemotherapy for non-small cell lung cancer (NSCLC) in a randomized prospective study. Thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) expression were investigated in resected tumors and the relationship between their expression and clinical factors in NSCLC patients was examined. Fifty-four NSCLC patients had undergone complete surgical resection and lymph node dissection, and had been administered UFT post-surgery. The TS and DPD expression in the tumor tissues was evaluated by immunohistochemical staining. The relationship between TS and/or DPD expression and clinicopathological factors was examined. There were 38 TS-negative and 16 TS-positive cases, and 22 DPD-negative and 32 DPD-positive cases. There was no significant difference between the patients with TS or DPD and those without TS or DPD in age, gender, histological type or p-stage. The 5-year survival rates of patients positive and negative for TS were 50.0 and 89.5%, while 10-year survival rates were 23.3 and 79.7%, respectively (p<0.001). The 5-year survival rates of TS-positive and TS-negative patients in p-stage I were 54.6 and 95.5%, while 10-year survival rates were 22.7 and 95.5%, respectively (p<0.001). There was no significant difference between DPD-positive and DPD-negative patients in prognosis. The oral administration of UFT after surgery might improve the survival of NSCLC patients when TS levels in tumor tissues are low. Immunohistochemical evaluation of TS and DPD expression may be useful for predicting the efficacy of UFT after complete resection in NSCLC.
Taeko Nagao, Yoshimi Bando, Mitsunori Sasa, Tadaoki Morimoto, Nobuya Sano, Toshiyuki Hirose and Akira Tangoku : False-positive in fine-needle aspiration cytology of breast disease can be reduced with p63 immunostaining- A preliminary report, Anticancer Research, Vol.26, No.6B, 4373-4378, 2006.
(要約)
Myoepithelial cells of the mammary gland are considered to be a key to distinguishing benign from malignant disease in fine-needle aspiration (FNA) cytology. However, identification of these cells with Papanicolaou staining is not easy. The identification of myoepithelial cells was investigated using p63 antibodies to carry out immunostaining of FNA specimens that had been used at the time of Papanicolaou staining for 37 patients who yielded false-positives in FNA. Positively-stained cells were observed in overlying cell clusters or the background in 67.6% of the patients. There is a possibility that over-diagnosis could have been avoided by performing p63 staining for these patients. The controls consisted of stamp samples of fresh specimens obtained from 23 patients at the time of surgery for invasive carcinoma and the results of p63 immunostaining did not reveal any positive staining of tumor cells. Accordingly, these results indicate that there is a strong likelihood that there is no invasive carcinoma when many p63-positive cells are observed in the tumor cell population or the background and that p63 immunostaining has the potential to aid in reducing false-positives at the time of FNA diagnosis of breast disease.
Junichi Seike, Takahiro Yoshida, Junko Honda, Takanori Miyoshi, Atsushi Umemoto and Akira Tangoku : A case of early relapsed multiple lung metastases after esophagectomy successfully treated with S-1/cisplatin therapy after docetaxel/5-fluorouracil/cisplatin therapy., The Journal of Medical Investigation : JMI, Vol.53, No.3-4, 321-324, 2006.
(要約)
A 55-year-old-male patient underwent subtotal esophagectomy for esophageal cancer (pT1b, N0, M0, stage II) in April 2005. The patient received postoperative chemotherapy (docetaxel 40 mg/body, 5-fluorouracil 750 mg/body, cisplatin 10mg/body: administered every 4 weeks) for 3 months. Six months postoperatively, routine follow up CT demonstrated multiple metastatic tumors in the bilateral lungs. Under the diagnosis of multiple lung metastases, the patient was hospitalized and received intensive chemotherapy with docetaxel 40 mg/week (day 1), 5-fluorouracil 500 mg/day (days 1-5), cisplatin 10 mg/day (days 1-5). After two weeks administration, the patient eagerly hoped for outpatient treatment. The treatment was changed to outpatient chemotherapy with S-1 100 mg/day (continuous administration for 3 weeks followed by rest for 1 week) and cisplatin 20 mg/every week. The treatment enabled the patient to keep working. Follow up CT showed disappearance of all tumors two months after TS-1/cisplatin chemotherapy. There were no obvious signs of recurrence 5 months after chemotherapy. The S-1/cisplatin therapy in the outpatient was thought to be one of the effective treatments in maintaining quality of life for the patient.
Kazuya Kondo, Yuji Takahashi, Yukiko Hirose, Taeko Nagao, Masaru Tsuyuguchi, Masato Hashimoto, Atsushi Ochiai, Yasumasa Monden and Akira Tangoku : The reduced expression and aberrant methylation of p16(INK4a) in chromate workers with lung cancer., Lung Cancer, Vol.53, No.3, 295-302, 2006.
(要約)
STUDY OBJECTIVES: It is known that chromium is one of the important inhaled carcinogens that cause lung cancer. Our previous studies revealed a variety of genetic changes in lung cancers from chromate-exposed workers (chromate lung cancer). However, the epigenetic effects of chromium are not understood. MATERIALS AND METHODS: We investigated the methylation of the p16 gene using a methylation-specific PCR method in 30 chromate lung cancers and 38 non-chromate lung cancers, and the expression of the p16 protein using immunohistochemistry in 25 chromate lung cancers. RESULTS: Ten (33%) chromate lung cancers showed methylation of the p16 promoter region. On the other hand, 10 (26%) of the non-chromate lung cancers also showed it. The frequency of p16 methylation in non-chromate lung cancer was 0%, 33% and 30% for low (< or =600), moderate (<600, >1000) and high (> or =1000) Brinkman indexes, respectively. However, the frequency of p16 methylation in chromate lung cancer was constant, irrespective of the Brinkman index. In chromate lung cancer, patients with chromate exposure of less than 15 years never had p16 methylation, while 40% (> or =25 years) or 43% (> or =15, <25 years) of patients with chromate exposure of more than 15 years did. In chromate lung cancer, chromate exposure, not smoking, mainly influenced the p16 methylation. Most of the chromate lung cancers with p16 methylation (85.7%) showed repression of the p16 protein. CONCLUSIONS: We speculate that not only genetic but also epigenetic alterations are involved in the carcinogenesis due to chromium.
Kansei Komaki, Nobuya Sano and Akira Tangoku : Problems in histological grading of malignancy and its clinical significance in patients with operable breast cancer., Breast Cancer, Vol.13, No.3, 249-253, 2006.
(要約)
Although the histological grading of malignancy in patients with operable breast cancer, typically consisting of three factors: tubular formation, mitotic counts, and nuclear atypia, plays an important role in identifying patients at high risk of recurrence, the most effective combination of factors is still not completely clear. In assessing prognosis, the problems of clinical application of the grade of malignancy are not only related to the assemblage of the factors employed, but also to the heterogeneity within the tumor and interobserver variations. In a review of the correlation between the histological grading system for malignancy in operable breast cancer patients and the recurrence rate, only the grade of nuclear atypia statistically correlated with the rate of recurrence. Furthermore, a grading system consisting of mitotic counts and nuclear atypia was more significantly correlated to the risk of recurrence than was the system based on the three factors described above. Concerning the heterogeneity of histologic features within the primary tumor, a system based on the grade of mitotic counts or nuclear atypia showed a high degree of heterogeneity, but a system based on the grade of tubular formation showed low heterogeneity and bimodal distribution.
(キーワード)
Breast Neoplasms / Humans / Neoplasm Staging / Prognosis
BACKGROUND: A clinical trial of Docetaxel was performed by tri-weekly administration in patients with advanced or recurrent breast cancer. However, careful observation is necessary for outpatients because serious neutropenia often occurs during the therapy. A bi-weekly schedule is recommended since weekly administration requires more visits to the hospital. Docetaxel is proved to express synergistic efficacy in combination with 5'-DFUR by induced dThdPase in vivo. But there are no clinical trials to evaluate efficacy of bi-weekly Docetaxel and 5'-DFUR combination therapy. PURPOSE: To evaluate safety, the recommended dose of Docetaxel and the efficacy of biweekly Docetaxel and 5'-DFUR combination therapy. PATIENTS AND METHODS: Patients with advanced or recurrent breast cancer within 1 regimen of prior chemotherapy and without prior use of both Docetaxel and 5'-DFUR were enrolled. 5'-DFUR was orally administered by 600 mg/day. Docetaxel was intravenously given for at least 2 cycles (8 weeks) by 30 mg/m(2) for level 1, 40 mg/m(2) for level 2 and 50 mg/m(2) for level 3. At each level with 3 cases enrolled,the maximum tolerated dose (MTD) level was defined as that in which 2 or 3 cases showed dose limiting toxicity (DLT). The recommended dose was defined as the dose before MTD level. Therapeutic safety was evaluated by analyses of adverse events with the recommended dose. RESULTS: MTD was in level 3 and the recommended dose of Docetaxel was 40 mg/m(2) of level 2. No DLT was observed in level 2, and this combination therapy seemed safe and feasible for outpatients. In addition, all 6 cases for whom therapeutic efficacy was evaluated expressed a clinical response.
(キーワード)
Administration, Oral / Aged / Ambulatory Care / Antineoplastic Combined Chemotherapy Protocols / Bone Neoplasms / Breast Neoplasms / Dose-Response Relationship, Drug / Drug Administration Schedule / Female / Floxuridine / Humans / Lung Neoplasms / Maximum Tolerated Dose / Middle Aged / Neoplasm Recurrence, Local / Taxoids
(文献検索サイトへのリンク)
● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 16770094
In our department, there were 313 thoracic surgeries for primary lung cancer from January 1994 to December 2003. We clinically reviewed for the operative and hospital death (n=18, 5.8%). The patients were 16 males and 2 females (70.6 +/- 5.6 years old). The surgical procedures were 4 pneumonectomies, 13 lobectomies (3 bronchoplasties) and 1 partial resection. The mean interval until postoperative death was 122.5 +/- 156.1 days. There were 5 direct operative deaths within 30 days (1.6%). There were 4 cancer deaths, 2 hemoptyses, 2 operative bleeding, 2 thromboses, 2 cerebral hemorrhages, 1 pyothorax, 1 pneumonia, 1 respiratory failure, 1 multiple organ failure after chemotherapy and 2 unexplained deaths. The patients with pneumonectomy or aged significantly had high mortality. For postoperative complications such as hemoptysis or bleeding, perioperative management that takes these issues into consideration is needed. Furthermore, we must carefully review the preoperative evaluation and combined treatment, because there were many cancer deaths among cases showing early recurrence and metastasis.
(キーワード)
Adenocarcinoma / Aged / Aged, 80 and over / Carcinoma, Squamous Cell / Female / Hospital Mortality / Humans / Lung Neoplasms / Male / Middle Aged / Pneumonectomy
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● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 16715882
Koichiro Kenzaki, Shoji Sakiyama, Kazuya Kondo, Mitsuteru Yoshida, Yukikiyo Kawakami, Masatsugu Takehisa, Hiromitsu Takizawa, Takanori Miyoshi, Yoshimi Bando, Akira Tangoku and Mingyao Liu : Lung regeneration: implantation of fetal rat lung fragments into adult rat lung parenchyma., Journal of Thoracic and Cardiovascular Surgery, Vol.131, No.5, 1148-1153, 2006.
(要約)
OBJECTIVE: The capability of regeneration of lung tissues in adults is limited after chronic destruction. Bone marrow-derived stem cells, retinoic acid, growth factors, and other approaches have been attempted to promote or facilitate this process. We hypothesized that fetal lung tissues, with great potential for growth and differentiation, could be used for lung regeneration. METHODS: Day 17 fetal lung tissue fragments at the pseudoglandular stage of lung development from Lewis rats were implanted into adult Lewis rat lungs. For group 1, fetal lung fragments were injected into the adult left lung parenchyma; for group 2, fetal fragments were injected with the left lung partially resected; for group 3, adult fragments were injected; and for groups 4 and 5, fetal fragments were implanted into the omentum and subcutaneous tissue, respectively. RESULTS: The grafts implanted into pulmonary parenchyma were differentiated with opening of the alveolar space after 4 weeks and were advanced further with morphologic features similar to those of neonatal lungs after 8 and 12 weeks. The implants were connected with pulmonary circulation determined by means of perfusion with India ink. These changes appeared to be further enhanced in animals with partial lung resection that might have facilitated the maturation of implanted fetal lung tissues through mechanical factors, soluble factors, or both. Fetal lung tissues did not mature when implanted into the omentum or subcutaneous tissue. Adult lung fragments did not expand after being reimplanted back into the same animal. CONCLUSIONS: Fetal lung tissue might be an option for further investigation into lung regeneration.
Takanori Miyoshi, Kazuya Kondo, Hiromitsu Takizawa, Koichiro Kenzaki, Haruhiko Fujino, Shoji Sakiyama and Akira Tangoku : Fluoroscopy-assisted thoracoscopic resection of pulmonary nodules after computed tomography--guided bronchoscopic metallic coil marking., Journal of Thoracic and Cardiovascular Surgery, Vol.131, No.3, 704-710, 2006.
(要約)
OBJECTIVE: To localize small and deeply situated pulmonary nodules during thoracoscopy with roentgenographic fluoroscopy, we developed a marking procedure that uses a metallic coil. METHODS: Nine patients underwent video-assisted thoracoscopic surgery for the removal of 11 pulmonary lesions. Fluoroscopy-assisted thoracoscopic surgery after computed tomography-guided bronchoscopic metallic coil marking was performed with an ultrathin bronchoscope, with simulation by means of virtual bronchoscopy. During thoracoscopy, a C-arm-shaped roentgenographic fluoroscope was used to detect the radiopaque nodules. RESULTS: The marking procedure took 15 to 60 minutes from insertion to removal of the bronchoscope. There were no complications from the marking, and all 11 nodules were easily localized by means of thoracoscopy. The metallic coil showed the nodules on the fluoroscopic monitor, which aided in nodule manipulation. Nodules were completely resected under thoracoscopic guidance, except in one case in which a minithoracotomy was performed at an early stage of the trial. The pathologic diagnosis was primary adenocarcinoma in 9 patients, pulmonary metastasis from colon cancer in 1 patient, and pulmonary lymph node in 1 patient. Two cases of bronchioloalveolar adenocarcinoma with an invasive component and a well-differentiated adenocarcinoma were converted to open thoracotomy to perform curative lobectomy. CONCLUSIONS: In this pilot study computed tomography-guided transbronchial metallic coil marking with an ultrathin bronchoscope with virtual bronchoscopic simulation might be a useful method for the fluoroscopy-assisted thoracoscopic resection of pulmonary nodules.
(キーワード)
Adult / Aged / Aged, 80 and over / Bronchoscopes / Bronchoscopy / Female / Fluoroscopy / Humans / Lung Neoplasms / Male / Middle Aged / Pilot Projects / Reproducibility of Results / Thoracic Surgery, Video-Assisted / Thoracoscopy / Tomography, X-Ray Computed
Hideto Hayashi, Akira Tangoku, Kazuyoshi Suga, Kensaku Shimizu, Katsuhiko Ueda, Shigefumi Yoshino, Toshihiro Abe, Tomomitsu Sato, Naofumi Matsunaga and Masaaki Oka : CT lymphography-navigated sentinel lymph node biopsy in patients with superficial esophageal cancer., Surgery, Vol.139, No.2, 224-235, 2006.
(要約)
BACKGROUND: To evaluate experimentally and clinically the feasibility of a newly developed technique of endoscopic computed tomography (CT) lymphography with endoscopic submucosal injection of iopamidol for esophageal sentinel lymph node (SLN) mapping and biopsy examination. METHODS: Nine anesthetized dogs underwent CT after endoscopic submucosal injection of 2 mL iopamidol; 1.25-mm thick CT images were obtained before and at 1, 3, 5, 7, and 10 minutes after contrast injection. Clinically, 12 patients with superficial esophageal cancer (preoperative imaging stage: cT1, cN0) underwent CT lymphography in a similar fashion at 1, 5, and 10 minutes after peritumoral injection, followed by radical esophagectomy and regional lymph node dissection under CT lymphography guidance. RESULTS: CT lymphography visualized the draining lymphatic vessels and SLNs within 5 minutes after contrast injection. All 14 SLNs in dogs (average, 1.5 nodes per animal; range, 1-2) and 28 SLNs in patients (average, 2.3 nodes per patient; range, 1-4) were found intraoperatively at the correct location under CT lymphography guidance. Lymph node metastasis could be detected with excellent sensitivity and accuracy in this small number of patients with no false-negative findings; metastasis was positive only in the preoperatively identified SLNs in 4 patients and in both SLNs and distant nodes in 1 patient, and was negative in all resected nodes in the remaining 7 patients. CONCLUSIONS: Endoscopic CT lymphography appears to allow accurate identification of direction and locations of lymph flow and SLNs, and has the potential clinical applicability for esophageal SLN mapping and biopsy examination, but will require a large study to determine its accuracy and usefulness.
Kazuyoshi Suga, Kensaku Shimizu, Yasuhiko Kawakami, Akira Tangoku, Mohammed Zaki, Naofumi Matsunaga and Masaaki Oka : Lymphatic drainage from esophagogastric tract: feasibility of endoscopic CT lymphography for direct visualization of pathways., Radiology, Vol.237, No.3, 952-960, 2005.
(要約)
PURPOSE: To evaluate the feasibility of an endoscopic computed tomographic (CT) lymphography technique with submucosal injection of iopamidol for direct visualization of lymphatic drainage pathways in dogs and in patients with operable esophageal cancer. MATERIALS AND METHODS: With institutional animal committee approval, a total of 2 mL of undiluted iopamidol was injected into the esophageal (n = 6) or gastric (n = 3) submucosa in nine dogs by using a flexible endoscope. Multi-detector row CT images (section thickness, 1.25 mm) were obtained before contrast material injection and during the 10 minutes after injection. The animals were euthanized so that their lymphatic anatomy could be examined. With ethical committee approval and patient informed consent, nine patients with esophageal cancer also underwent CT lymphography with peritumoral injection of 2 mL of iopamidol, followed by esophagectomy and regional lymph node dissection with CT lymphographic guidance. The histopathologic features of dissected nodes, including sentinel lymph nodes (SLNs), were examined. RESULTS: CT lymphography depicted the direct connection of lymphatic drainage vessels with enhanced and/or unenhanced nodes (ie, SLNs) as early as within 5 minutes after contrast material injection in all subjects. All 13 SLNs in dogs (1.4 nodes per animal) and 18 SLNs in patients (two nodes per patient) were found and dissected at the correct location by using CT lymphographic guidance. In patients, histopathologic examination revealed the high predictive value of CT lymphographic-guided SLN biopsy: Only one of the preoperatively identified SLNs in three patients and both SLNs and adjacent nodes in two patients were positive for metastasis; all resected nodes in the remaining four patients were negative. CONCLUSION: Endoscopic CT lymphography is a feasible method for visualizing the direct connection between and the accurate anatomic location of SLNs and lymphatic drainage vessels.
BACKGROUND: FEC (5-FU+epirubicin+cyclophosphamide) therapy has been used as adjuvant chemotherapy for breast cancer patients with nodes positive. The aim of this study was to evaluate host immunity and side effects of the FEC therapy. The effect of oral administration of Lentinus edodes mycelia (LEM) was also observed. METHODS: Ten patients were enrolled in this study. The treatment with 5-FU (500 mg/m2), epirubicin (75 mg/m2) and cyclophosphamide (500 mg/m2) was administered every 21 days for 2 cycles, and LEM (9 g/day po) was administered during the 2nd cycle. RESULTS: NK cell activity and the number of white blood cells decreased on the 7th day after the therapy, and they recovered on the 21st day. However, this NK cell activity and the number of white blood cells didn't decrease when the FEC therapy was used with LEM po. CONCLUSIONS: FEC 75 therapy has made some impacts on host immunity, and LEM with the FEC 75 therapy might have prevented host immunity.
Kazuya Kondo, Takanori Miyoshi, Hiromitsu Takizawa, Koichiro Kenzaki, Shoji Sakiyama and Akira Tangoku : Photodynamic therapy for submucosal tumor of the central bronchus, The Journal of Medical Investigation : JMI, Vol.52, No.3,4, 208-211, 2005.
(要約)
A 75-year-old man was referred to our hospital because of the emphysema and tumor of the right intermediate bronchus. Thoracic CT scan and bronchoscopic examination demonstrated a spherical tumor of the right intermediate bronchus covering a normal mucosa. The biopsy specimen obtained from this tumor was histologically diagnosed as "glandular type of adenocarcinoma in the bronchus". Surgical treatment was not feasible because of poor pulmonary function. Therefore, the patient underwent Photodynamic therapy (PDT) using porfimer sodium (Photofrin) and an excimer dye laser. After 4 months, the tumor disappeared and there has been no recurrence for 3 years 3 months. PDT can affect a submucosal tumor of the central airway, and is safe for patients with poor pulmonary function. Our report recommends that PDT should be applied not only to early lung cancer but also submucosal tumor of the central bronchus.
OBJECTIVE: Three-dimensional multidetector-row computed tomographic lymphography (3D MDCT-LG) with interstitial injection of a widely available nonionic monometric contrast medium iopamidol was used for navigation of breast sentinel lymph node (SLN) biopsy. METHODS: 3D MDCT-LG was obtained after massage of the interstitially injection sites of a total of 4-5 mL undiluted iopamidol at periareolar and peritumoral areas in 68 consecutive patients with early-stage breast cancer, using a 4 detector-row CT scanner. Drainage lymphatic patterns and SLN anatomy were assessed on 3D MDCT-LG images. 3D MDCT-LG-navigated SLN biopsy with combined use of blue dye was followed by backup axillary lymph node dissection to evaluate accuracy of SLN biopsy. RESULTS: The 3D MDCT-LG images clearly localized primary SLNs by visualizing the direct connection between these nodes and their afferent lymphatic vessels on detailed anatomy of the surrounding structures in all patients. Drainage lymphatic pathways on these images were classified into 4 patterns: single route/single SLN (39 cases, 57%), multiple routes/multiple SLNs (10 cases, 15%), single route/multiple SLNs (9 cases, 13%), and multiple routes/single SLN (10 cases, 15%). Under 3D MDCT-LG navigation, SLNs was found at the accurate location in all patients. With backup axillary lymph node dissection, metastasis was found in 14 (20%) patients, and 8 of these patients had metastasis only in the preoperatively identified SLNs. In other 5 positive patients, metastasis was found both in the SLN and non-SLNs. However, micrometastasis eventually was found only in non-SLN in an elderly patient. Overall, the sensitivity, false-negative rate, and accuracy of 3D CT-L-navigated SLN biopsy were 92% (13/14 patients), 7% (1/14 patients), and 98% (67/68 patients), respectively. CONCLUSIONS: Topographic 3D interstitial MDCT-LG can be a widely available and reliable navigator for breast SLN biopsy.
(キーワード)
Adult / Aged / Aged, 80 and over / Breast Neoplasms / Contrast Media / False Negative Reactions / Female / Humans / Imaging, Three-Dimensional / Iopamidol / Mammography / Middle Aged / Sensitivity and Specificity / Sentinel Lymph Node Biopsy / Tomography, X-Ray Computed
Masatsugu Takehisa, Taeko Nagao, Mitsuteru Yoshida, Toshiyuki Hirose, Aiichiro Kajikawa, Mitsunori Sasa and Akira Tangoku : Lower axillary dissection in breast cancer surgery may be candidate for cases with early breast cancer., The Journal of Medical Investigation : JMI, Vol.52, No.1-2, 74-79, 2005.
(要約)
Lower axillary lymph node dissection (lower parts of both the level I and II elements below the second intracostobrachial nerve) and level I and II lymph node dissection were performed on breast cancer patients (n = 54), and the results with the two methods were compared in terms of the status of detected lymph node metastases. For Stage I, N0 cases, the results for pathological classification lymph node metastases (pN) were in agreement between the two dissection methods. And, the occurrence of operated arm swelling wasn't recognized when a side effect was examined with the case (n = 28) that only lower axillary dissection was carried out in case of an operation for breast cancer. Accordingly, it was surmised that lower axillary dissection provides accurate pN information for Stage I, N0 cases. These results indicate that lower axillary dissection has the potential to become an effective, standard surgical procedure for breast cancer patients whose preoperative disease stage is Stage I.
A Morimoto, E Yasuno, Y Kinouchi, Y Ohmine, Akira Tangoku and T Morimoto : Spatial resolution in the electrical impedance tomography for the local tissue., Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society, Vol.6, 6638-6641, 2005.
(要約)
Electrical impedance tomography (EIT) is one of the medical tissue diagnosis devices and it creates a two- or three-dimensional image of electrical impedance distribution in a living tissue. It is used for imaging the information of tissue structures, and physiological functions and states of the tissue. However, there are several problems to achieve the practical use of EIT, which are an inverse algorithm for estimating parameters and electrode structure and so on. EIT is calculated from impedance data, which is measured non-invasively by surface electrodes. Therefore, it is important to choose a proper electrode structure to realize a practical EIT measurement system. In this study, we used a electrode structure, called "divided electrode", which is proposed for a short time measurement of bio-impedance in a cross section of the local tissue. Its capability is examined by computer simulations, where a distributed equivalent circuit is used as a model for the cross section tissue. Estimation of impedance parameters is carried out by use of the Newton method. The objective of this study is to examine the spatial resolution on the circuit model. Moreover, the current flowing in the circuit model is examined.
Yoshitaka Maeda, Minekatsu Nishida, Takashi Takao, Naohide Mori, Takao Tamesa, Akira Tangoku and Masaaki Oka : Risk factors for postoperative liver failure after hepatectomy for hepatocellular carcinoma., Hepato-Gastroenterology, Vol.51, No.60, 1792-1796, 2004.
(要約)
BACKGROUND/AIMS: Selection of patients for hepatectomy for hepatocellular carcinoma conventionally has been based upon Child-Pugh grading. However, postoperative liver failure after hepatectomy is a major cause of hospital mortality. A new predictor of postoperative liver failure is required. The objective of this study was to identify risk factors for postoperative liver failure after hepatectomy. METHODOLOGY: Perioperative risk factors for liver failure after hepatectomy were analyzed in 112 patients with hepatocellular carcinoma Eight of these patients died of liver failure. Stepwise multivariate logistic regression was performed to investigate significant independent factors among 17 variables, including the serum alkaline phosphatase ratio (ALPR) on the first day after hepatectomy. ALPR was calculated as the postoperative ALP level divided by the ALP level before surgery. RESULTS: Significant risk factors of postoperative liver failure were ALPR on postoperative day 1 (ALPR1), sex, operative blood loss, and operative procedure. As an indicator of liver failure, the diagnostic accuracy of the ALPR1 was 93.7% when the ALPR was less than 0.4 on the first postoperative day. The ALPR and the serum total bilirubin concentration after hepatectomy were uncorrelated. CONCLUSIONS: ALPR1 is a useful predictor of liver failure after hepatectomy.
Hiroaki Toshimitsu, Kiichiro Hashimoto, Akira Tangoku, Norio Iizuka, Kohtaro Yamamoto, Shigeto Kawauchi, Atsunori Oga, Tomoko Furuya, Masaaki Oka and Kohsuke Sasaki : Molecular signature linked to acquired resistance to cisplatin in esophageal cancer cells., Cancer Letters, Vol.211, No.1, 69-78, 2004.
(要約)
To clarify the molecular basis of acquired cisplatin (CDDP) resistance in esophageal squamous cell carcinoma (ESCC), we used cDNA microarray technology. A CDDP-resistant cell line (YES-2/CDDP), which shows a 7.5-fold increase in resistance to CDDP and a 3-fold decrease in CDDP accumulation compared with the parental YES-2 ESCC cell line, was generated from YES-2 by exposure to increased concentrations of CDDP. By cDNA microarray analysis, we identified 44 genes with significantly different expression levels between YES-2/CDDP and YES-2 cells. Interestingly, 15 of these 44 genes encoded ribosome-related proteins, almost all of which were underexpressed in YES-2/CDDP cells. Our present data suggest that many ribosome-related genes may be involved in the acquired resistance to CDDP in ESCC and that such information may allow us to better understand the mechanism of CDDP resistance.
Norio Iizuka, Masaaki Oka, Hisafumi Yamada-Okabe, Kenji Hamada, Hironobu Nakayama, Naohide Mori, Takao Tamesa, Toshimasa Okada, Norikazu Takemoto, Katsuhiro Matoba, Motonari Takashima, Katsuhiko Sakamoto, Akira Tangoku, Takanobu Miyamoto, Shunji Uchimura and Yoshihiko Hamamoto : Molecular signature in three types of hepatocellular carcinoma with different viral origin by oligonucleotide microarray, International Journal of Oncology, Vol.24, No.3, 565-574, 2004.
(要約)
Chronic infection with hepatitis B or C virus (HBV or HCV) is the most clearly established risk factor for hepato-cellular carcinoma (HCC). One type of HCC (non-B, non-C HCC) also appears to develop in patients negative for both HBV and HCV. Using a supervised learning method, we investigated gene expression in 11 non-B, non-C HCCs with high-density oligonucleotide microarrays, and compared the patterns of gene expression with those of HBV-infected HCCs (B-type HCCs) and HCV-infected HCCs (C-type HCCs) in the previous dataset. Our gene selection identified 112 and 64 genes that were differentially expressed in non-B, non-C HCC in comparison with B- and C-type HCCs, respectively. In both gene selections, we found that the false discovery rate, the percentage of genes identified by chance, was less than 5%. Additionally, in combination with the previous data, our present data revealed a set of genes specific to each type of B- and C-type HCCs and non-B, non-C HCC. Among these, an interferon-induced gene, IFI27, was differentially expressed among all three types of HCCs, and this result was confirmed by RT-PCR. Thus, our present study provides a framework to characterize the molecular features in the three subtypes of HCC with different viral origin.
(キーワード)
DNA Chip / Microarray / Gene Expression Profiles / Hepatocellular Carcinoma / Hepatitis B Virus / Hepatitis C Virus
(文献検索サイトへのリンク)
● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 14767541
Akira Tangoku, Shigeru Yamamoto, Kazuyoshi Suga, Katsuhiko Ueda, Yukiko Nagashima, Makoto Hida, Tomomitsu Sato, Kazuhiko Sakamoto and Masaaki Oka : Sentinel lymph node biopsy using computed tomography-lymphography in patients with breast cancer, Surgery, Vol.135, No.3, 258-265, 2004.
(要約)
The sentinel lymph node biopsy (SLNB) technique is established in the treatment of breast cancer. The current technique of mapping the SLN with blue dye or radiotracers requires a learning period. Tracer and injection site selection and intraoperative pathologic examination have been discussed. We developed a three-dimensional computed tomography lymphography (3D CT-LG) technique with commercially available iopamidol. SLNB and backup dissection were performed in 40 patients with T1 and T2 breast cancer. Feasibility and efficacy of CT-LG were examined. In all patients, lymph flow and the surrounding anatomical environment were visualized with 3D CT-LG. SLNB was successful because of accurate navigation by 3D CT-LG. SLN was detected in all patients, whereas dye navigation failed in seven fatty axilla and two patients with prior excisional biopsy. Backup dissection confirmed the accuracy of CT-LG-guided SLNB. A false negative result was found in only one patient. Preoperative prediction was feasible in cases of SLN metastasis. CT-LG allowed accurate SLN localization by quickly and adequately visualizing the direct connection between the SLN and its afferent lymphatic vessels. Detailed cross-sectional images of lymphatic anatomy during CT resulted in successful SLNB with shortening of the presurgical examination schedule.
(キーワード)
Adult / Aged / Breast Neoplasms / Breast Neoplasms, Male / Female / Humans / Lymphography / Male / Middle Aged / Sentinel Lymph Node Biopsy / Tomography, X-Ray Computed
Kazuyoshi Suga, Yue Yuan, Munemasa Okada, Naofumi Matsunaga, Akira Tangoku, Shigeru Yamamoto and Masaaki Oka : Breast sentinel lymph node mapping at CT lymphography with iopamidol: preliminary experience, Radiology, Vol.230, No.2, 543-552, 2004.
(要約)
To evaluate sentinel lymph node (SLN) mapping with interstitial computed tomographic (CT) lymphography with small volumes of iopamidol for direction of SLN biopsy in breast cancer. Thin-section transverse and three-dimensional CT images that included the breast and axilla were acquired at multi-detector row helical CT in 17 patients with operable breast cancer before subcutaneous injection of 2 mL of undiluted iopamidol into peritumoral and periareolar areas and 1-5 minutes after massage of injection sites. Location and size of SLNs were assessed at CT lymphography and were compared with SLNs at standard axillary lymph node dissection with blue dye staining. CT lymphography allowed localization of SLNs in all patients by means of visualization of a direct connection between an SLN and its afferent lymphatic vessels draining from the injection sites. Afferent vessels were joined and drained into a single axillary SLN, except in four patients with two or three SLNs, including a parasternal one. SLNs did not enhance because of rerouting of lymph flow in four patients. At surgery, SLNs that were stained or not stained with blue dye were easily found with CT lymphographic guidance. Tumoral infiltration was not evident in any resected nodes, except for infiltration in one patient with micrometastasis in SLN alone and infiltration in four patients with massive metastasis in both SLN and distant nodes. Because preoperative CT lymphography-guided SLN mapping provides SLN position with detailed lymphatic anatomy, it may be useful for the direction of breast SLN biopsy.
Kiichiro Hashimoto, Naohide Mori, Takao Tamesa, Toshimasa Okada, Shigeto Kawauchi, Atsunori Oga, Tomoko Furuya, Akira Tangoku, Masaaki Oka and Kohsuke Sasaki : Analysis of DNA copy number aberrations in hepatitis C virus-associated hepatocellular carcinomas by conventional CGH and array CGH, Modern Pathology, Vol.17, No.6, 617-622, 2004.
(要約)
To clarify the genetic aberrations involved in the development and progression of hepatitis C virus-associated hepatocellular carcinoma (HCV-HCC), we investigated DNA copy number aberrations (DCNAs) in 19 surgically resected HCCs by conventional CGH and array CGH. Conventional CGH revealed that increases of DNA copy number were frequent at 1q (79% of the cases), 8q (37%), 6p (32%), and 10p (32%) and that decreases were frequent at 17p (79%), 16q (58%), 4q (53%), 13q (42%), 10q (37%), 1p (32%), and 8p (32%). In general, genes that showed DCNAs by array CGH were usually located in chromosomal regions with DCNAs detected by conventional CGH analysis. Increases in copy numbers of the LAMC2, TGFB2, and AKT3 genes (located on 1q) and decreases in copy numbers of FGR/SRC2 and CYLD (located on 1p and 16q, respectively) were observed in more than 30% of tumors, including small, well-differentiated carcinomas. These findings suggest that these genes are associated with the development of HCV-HCC. Increases of MOS, MYC, EXT1, and PTK2 (located on 8q) were detected exclusively in moderately and poorly differentiated tumors, suggesting that these alterations contribute to tumor progression. In conclusion, chromosomal and array CGH technologies allow identification of genes involved in the development and progression of HCV-HCC.
Toshimasa Okada, Norio Iizuka, Hisafumi Yamada-Okabe, Naohide Mori, Takao Tamesa, Norikazu Takemoto, Akira Tangoku, Kenji Hamada, Hironobu Nakayama, Takanobu Miyamoto, Shunji Uchimura, Yoshihiko Hamamoto and Masaaki Oka : Gene expression profile linked to p53 status in hepatitis C virus-related hepatocellular carcinoma, FEBS Letters, Vol.555, No.3, 583-590, 2003.
(要約)
To clarify the role of p53 in 22 hepatitis C virus (HCV)-infected hepatocellular carcinomas (HCCs), we compared the gene expression profiles of HCCs with wild-type p53 (wt-p53) (n=17) and those with mutant-type p53 (mt-p53) (n=5) by oligonucleotide microarray analysis. Among 83 p53-related genes identified by a supervised learning method, 25 were underexpressed, and 58 were overexpressed in mt-p53 HCCs compared with wt-p53 HCCs. With a computer search, we identified consensus p53-binding sequences in the 3-kb region upstream of the translation initiation site in 59 of the 83 genes, suggesting that the in vivo p53-associated transcription system is very complicated. These data will provide additional insights into p53-related pathogenesis in HCV-infected HCC.
Norio Iizuka, Masaaki Oka, Kohtaro Yamamoto, Akira Tangoku, Koji Miyamoto, Takanobu Miyamoto, Shunji Uchimura, Yoshihiko Hamamoto and Kiwamu Okita : Identification of common or distinct genes related to antitumor activities of a medicinal herb and its major component by oligonucleotide microarray, International Journal of Cancer, Vol.107, No.4, 666-672, 2003.
(要約)
Although the physiological actions of many herbs are gradually being elucidated at the molecular level, it remains unclear how individual components of herbs contribute to their biological activities. In the present study, the antiproliferative activity of Coptidis rhizoma, a medicinal herb, and the major component berberine was investigated in 8 human pancreatic cancer cell lines. Gene expression patterns associated with sensitivities to each agent were analyzed with oligonucleotide arrays that comprised approximately 11,000 genes. We used a tetrazolium dye (MTT) assay to determine ID(50) values after the 8 cell lines were exposed to the 2 agents for 72 hr. The ID(50) value for berberine was correlated positively with that for C. rhizoma (r=0.725, p=0.0401). C. rhizoma killed tumor cells more effectively than purified berberine when normalized to the level of berberine present in the herb. From the oligonucleotide array data, we selected 20 and 13 genes with strong correlations (r(2)>0.81) to ID(50) values for berberine and C. rhizoma, respectively. Among these 33 genes, the levels of expression of 12 were correlated with the ID(50) values of both agents, suggesting that these genes are associated with tumor-killing activity of berberine in C. rhizoma. Expression of the remaining 21 genes was correlated with the ID(50) value of either purified berberine or C. rhizoma. Thus, we identified common and distinct genes responsible for anti-proliferative activities of purified berberine and C. rhizoma. This strategy may improve our understanding of the actions of herbs with antitumor activities.
(キーワード)
Coptidis rhizoma / Herb / Berberine / DNA chip / Pancreatic cancer
Takashi Ueno, Akira Tangoku, Shigefumi Yoshino, Toshihiro Abe, Hideto Hayashi, Hiroaki Toshimitsu, Kiichiro Hashimoto, Tomomitsu Satoh, Atsunori Oga, Tomoko Furuya, Masaaki Oka and Kohsuke Sasaki : Prediction of nodal metastasis by comparative genomic hybridization in biopsy specimens from patients with superficial esophageal squamous cell carcinoma, Clinical Cancer Research, Vol.9, No.14, 5137-5141, 2003.
(要約)
Selection of appropriate protocols for treatment of superficial esophageal squamous cell carcinoma (SESCC) is dependent on lymph node metastasis status. Therefore, it is important to know whether lymph node metastasis is present before treatment. In this study, we examined the relation between DNA sequence copy number aberrations detected by comparative genomic hybridization and lymph node metastasis in 26 surgically resected SESCCs (training samples). We then assessed whether the genetic information is predictive for nodal status in biopsy specimens from eight newly enrolled patients with SESCC (blinded samples). Pathological examination revealed that 17 of 26 training samples (65.4%) did not have associated lymph node metastasis. Gains of 8q24 and/or 20q12-qter were observed in 12, including all (nine of nine) with nodal metastasis. Fourteen training samples did not have gain of either 8q24 or 20q12-qter. Of the blinded samples, two showed no gain of 8q24 or 20q12-qter, and as anticipated the postoperative pathological examination revealed no nodal metastasis. The remaining six blinded samples had gains of 8q24 and/or 20q12-qter, and lymph node metastasis was detected by postoperative examination in four of these tumors. Absence of gains of 8q24 and/or 20q12-qter appears to be associated with absence of lymph node metastasis in patients with SESCC; therefore, less invasive surgery can be chosen.
(キーワード)
Aged / Aged, 80 and over / Biopsy, Needle / Carcinoma, Squamous Cell / Chromosomes, Human, Pair 20 / Chromosomes, Human, Pair 8 / DNA, Neoplasm / Esophageal Neoplasms / Female / Gene Amplification / Humans / Lymph Nodes / Lymphatic Metastasis / Male / Middle Aged / Nucleic Acid Hybridization / Postoperative Care / Predictive Value of Tests
(文献検索サイトへのリンク)
● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 14613991
Hiroshi Araki, Takashi Ueno, Akira Tangoku, Shugefumi Yoshino, Toshihiro Abe, Shigeto Kawauchi, Atsunori Oga, Tomoko Furuya, Masaaki Oka and Kohsuke Sasaki : Detection of amplified oncogenes by genome DNA microarrays in human primary esophageal squamous cell carcinoma:comparison with conventional comparative genomic hybridization analysis, Cancer Genetics and Cytogenetics, Vol.146, No.1, 16-21, 2003.
(要約)
Oncogene amplification in 20 surgically resected esophageal squamous cell carcinomas (ESCC) was examined with DNA microarrays that detected 57 oncogenes and two reference DNA. Alterations in DNA copy numbers detected by microarrays were compared to those obtained by conventional comparative genomic hybridization (CGH). Amplification of eight oncogenes (CCND1, FGF3/FGF4, EMS1, SAS, ERBB2, PDGFRA, MYC, and BCL2) was detected by DNA microarrays in 9 of 20 tumors. Although ERBB2 was 23.2 times higher than the control level in one case, the average magnitude of gene amplification was approximately two to four times that of the control level. EMS1, CCND1, and FGF3/FGF4, which are all located on 11q13, were amplified in 7, 5, and 4 of 20 ESCC, respectively, and they were coamplified in 3 tumors. A comparison of genome DNA microarrays and CGH data revealed that although most amplified oncogenes were included in chromosomal regions for which DNA copy number gains were detected by conventional CGH, not all amplified genes on microarrays showed concomitant DNA copy number gains on CGH. In conclusion, microarrays of oncogenes are useful for the comprehensive identification of amplified oncogenes and for analysis of areas of specific amplification within chromosomal regions with DNA copy number increases detected by CGH analysis.
(キーワード)
Aged / Aged, 80 and over / Carcinoma, Squamous Cell / DNA / Esophageal Neoplasms / Female / Gene Amplification / Humans / Male / Middle Aged / Nucleic Acid Hybridization / Oligonucleotide Array Sequence Analysis / Oncogenes
It is very important to control the Th2-dominant condition in cancer patients while they are undergoing immunotherapy. OK-432 powerfully guides Th1 cytokine, but sometimes it can not eliminate the Th2 dominant state in cancer patients, which is needed to induce Th2 cytokine. Premedication with combined LTN and OK-432 is an effective therapy for controlling the Th1/Th2 balance. We tried administering LTN and OK-432 in the pleural or peritoneal cavity for patients with malignant effusion. Of all 9 lesions of the 8 cases, 6 showed complete remission and 1 showed partial response. The level of IL-12 (p70) and IFN-gamma in the pleural effusion or ascites of the combination group was higher than the OK-432 only group. In conclusion, LTN and OK-432 combined therapy appears to be an effective local treatment.
A 49-year-old woman was admitted to our hospital because of hepatocellular carcinoma (HCC). She had no hepatitis virus. Serum AFP and PIVKA-II levels were as high as AFP 329.4 ng/ml (AFP-L3% 73.1%) and 281 AU, respectively. Portal venous thrombus was observed from the right portal branch to left portal branch and superior mesenteric vein. An extended right hemihepatectomy with extraction of portal venous thrombus was performed. On postoperative day 8, low-dose cisplatin (10 mg/day for 5 days/week) and 5-fluorouracil (250 mg/day for 5 days/week) were administered through the hepatic artery for 4 weeks. After chemotherapy, one intrahepatic metastasis appeared and RFA was performed for this tumor. At 16 months after surgery, she had multiple lymph node metastases and died at 20 months after the surgery without intrahepatic metastasis. Low-dose CDDP/5-FU intra-hepatic artery infusion chemotherapy was effective for prevention of intrahepatic recurrence after resection of HCC with portal venous thrombus.
It is difficult to evaluate surgical stress of patients with hepatocellular carcinoma (HCC). Cytokine production from the liver is decreased due to the liver dysfunction that is usually associated with HCCs. Therefore, we evaluated surgical stress after hepatectomy by measuring intracellular cytokines of lymphocytes in peripheral blood. We examined 22 patients with digestive cancers (8 with HCC, 10 with gastric cancer, and 4 with esophageal cancer). The concentrations of serum IL-6 levels 6 h after hepatectomy, gastrectomy, and esophagectomy were 268 +/- 84, 309 +/- 93, and 1,323 +/- 364 pg/ml, respectively. There was no significant difference between hepatectomy and gastrectomy, though based on clinical observations, it is estimated the surgical stress of hepatectomy was greater than that of gastrectomy. Conversely, the percentage of CD4+IL-6+ cells 6 h after surgery was 8.5 +/- 2.8, 3.3 +/- 0.6, and 7.8 +/- 3.4%, respectively. The percentage of CD4+IL-6+ cells after hepatectomy was significantly higher than that after gastrectomy. We estimated that the percentage of CD4+IL-6+ cells was an appropriate indicator of surgical stress on HCC, because the percentage of CD4+IL-6+ cells correlated well with the duration of surgery more than did the serum IL-6 levels. These results suggest that the percentage of CD4+IL-6+ cells may help in accurately evaluating surgical stress in patients with liver dysfunctions such as HCC.
Esophageal diverticula are considered to be rare but this has not deterred interest in the condition, either historically or in the present era. Most parabronchial esophageal diverticula are traction diverticula, and resection is thought to be unnecessary. The majority of pharyngoesophageal diverticula and epiphrenic diverticula are pulsion diverticula. It is now well accepted that they correlate with underlying motor disturbance and that surgery is indicated. If there is motor disturbance is preoperative manometry, it is necessary to add myotomy. However, if there is no motor disturbance, the surgical management remains controversial. Recently, minimal access surgery with laparoscopy or thoracoscopy has been successful in the treatment of epiphrenic diverticulum.
Norio lizuka, Masaaki Oka, Hisafumi Yamada-0kabe, Naohide Mori, Takao Tamesa, Toshimasa Okada, Norikazu Takemoto, Kiichiro Hashimoto, Akira Tangoku, Kenji Hamada, Hironobu Nakayama, Takanobu Miyamoto, Shunji Uchimura and Yoshihiko Hamamoto : Differential gene expression in distinct virologic types of hepatocellular carcinoma: association with liver cirrhosis, Oncogene, Vol.22, No.19, 3007-3014, 2003.
(要約)
Using oligonucleotide microarray data of 45 hepatocellular carcinoma (HCC) samples, we evaluated gene expression in hepatitis B virus-positive and hepatitis C virus-positive HCCs (HBV- and HCV-HCCs) for an association with liver cirrhosis (LC). In all, 89 genes were expressed differentially between HBV-HCCs associated with LC and those not associated with LC. Among them, tumors from LC patients showed significantly lower expression levels of 72 genes and significantly higher levels of 17 genes than the levels found in tumors from non-LC patients. The former included genes responsible for signal transduction, transcription, metabolism, and cell growth. The latter included a tumor suppressor gene and a cell-growth-related gene. Only eight genes were expressed differentially between HCV-HCCs associated with and without LC. Our findings provide as a framework for clarifying the role of LC in HBV- and HCV-related hepatocarcinogenesis.
Norio Iizuka, Masaaki Oka, Hisafumi Yamada-Okabe, Minekatsu Nishida, Yoshitaka Maeda, Naohide Mori, Takashi Takao, Takao Tamesa, Akira Tangoku, Hisahiro Tabuchi, Kenji Hamada, Hironobu Nakayama, Hideo Ishitsuka, Takanobu Miyamoto, Akira Hirabayashi, Shunji Uchimura and Yoshihiko Hamamoto : Oligonucleotide microarray for prediction of early intrahepatic recurrence of hepatocellular carcinoma after curative resection, The Lancet, Vol.361, No.9361, 923-929, 2003.
(要約)
Hepatocellular carcinoma has a poor prognosis because of the high intrahepatic recurrence rate. There are technological limitations to traditional methods such as TNM staging for accurate prediction of recurrence, suggesting that new techniques are needed. We investigated mRNA expression profiles in tissue specimens from a training set, comprising 33 patients with hepatocellular carcinoma, with high-density oligonucleotide microarrays representing about 6000 genes. We used this training set in a supervised learning manner to construct a predictive system, consisting of 12 genes, with the Fisher linear classifier. We then compared the predictive performance of our system with that of a predictive system with a support vector machine (SVM-based system) on a blinded set of samples from 27 newly enrolled patients. Early intrahepatic recurrence within 1 year after curative surgery occurred in 12 (36%) and eight (30%) patients in the training and blinded sets, respectively. Our system correctly predicted early intrahepatic recurrence or non-recurrence in 25 (93%) of 27 samples in the blinded set and had a positive predictive value of 88% and a negative predictive value of 95%. By contrast, the SVM-based system predicted early intrahepatic recurrence or non-recurrence correctly in only 16 (60%) individuals in the blinded set, and the result yielded a positive predictive value of only 38% and a negative predictive value of 79%. Our system predicted early intrahepatic recurrence or non-recurrence for patients with hepatocellular carcinoma much more accurately than the SVM-based system, suggesting that our system could serve as a new method for characterising the metastatic potential of hepatocellular carcinoma.
(キーワード)
Carcinoma, Hepatocellular / Female / Gene Expression Profiling / Humans / Liver Neoplasms / Male / Middle Aged / Neoplasm Recurrence, Local / Oligonucleotide Array Sequence Analysis / Predictive Value of Tests
Kazuyoshi Suga, Nobuhiko Ogasawara, Yuan Yue, Munemasa Okada, Naofumi Matsunaga and Akira Tangoku : Visualization of Breast Lymphatic Pathways With an Indirect Computed Tomography Lymphography Using a Nonionic Monometric Contrast Medium Iopamidol: Preliminary Results, Investigative Radiology, Vol.38, No.2, 73-84, 2003.
(要約)
The capability of an indirect computed tomographic lymphography (CT-LG) using a nonionic monometric contrast medium iopamidol for visualizing breast lymphatic pathways was preliminarily tested. In 10 female dogs, a total of 0.5 and 1 mL of undiluted iopamidol was injected subcutaneously into the skin areas overlying the both caudal mammary glands. Contiguous 2-mm-thick multidetector raw helical CT images were obtained through the upper thorax and axilla before and during 60 minutes after gentle massage at the injection sites, with reconstruction into three-dimensional (3D) postcontrast CT images. The first lymph node (1st LN) directly draining from the injection sites was marked under CT guidance, followed by pre- and postmortem examinations. This CT-LG with 2-mL iopamidol was also attempted in five human female volunteers. Even with 0.5-mL iopamidol, the CT-LG clearly visualized the direct connection of the 1st LN and lymphatic vessels draining from the injection sites throughout the examination time in all the animals, with the maximum CT attenuation of 269 Hounsfield units (HU) +/- 137 in the 1st LN on the first postcontrast images. The topographic 3D images provided comprehensive anatomic outlines of these lymphatic pathways. Of the total of 20 opacified 1st LN and 110 distant nodes, all the 1st LN (100%) and 92 (83.6%) distant nodes could be resected at pre- or postmortem, with a good correlation with the CT images. The CT-LG also effectively localized the 1st LN with the maximum attenuation of 223 HU +/- 63 in the human volunteers, without any significant late adverse effects. Indirect CT-LG with iopamidol may have excellent potential for visualizing breast lymphatic drainage and for preoperative localization of breast sentinel lymph nodes.
Koji Matsuoka, Tomio Ueno, Katsuhiko Morita, Hiroo Kawano, Kazuhito Yamaguchi, Tsuyoshi Maekawa, Akira Tangoku and Masaaki Oka : Effects of moderate hypothermia on proinflammatory cytokine production in a rat model of caerulein-induced pancreatitis, Pancreas, Vol.26, No.1, e12-e17, 2003.
(要約)
Proinflammatory cytokines act as mediators of the local and systemic manifestations of acute pancreatitis (AP). To investigate whether moderate hypothermia (MH) (32 degrees C) can reduce the severity of AP by inhibiting cytokine production in a rat model of caerulein-induced pancreatitis. Rats were divided into three groups: control rats (Group I), AP rats treated with normothermia (38 degrees C) (Group II), and AP rats treated with MH (Group III). AP was induced by intramuscular injection of caerulein and intraperitoneal infusion of lipopolysaccharide. MH was induced 4 hours after the first caerulein injection. Serum interleukin (IL)-1beta, tumor necrosis factor (TNF)-alpha, IL-6, amylase, and lipase levels were determined 8 hours after the first injection. The pancreas and lung were examined histologically. MH in comparison with normothermia significantly reduced serum levels of IL-1beta, TNF-alpha, IL-6, amylase, and lipase. Histologically, the MH group showed less vacuolization of the acinar cells and cellular infiltration into the interacinar areas of the pancreas than were shown in the normothermia group, but these effects were not evident in the lung. Our results suggest that MH may be clinically applicable for reducing the severity of AP.
Norio Iisuka, Naohide Mori, Takuo Tamesa, Akira Tangoku and Masaaki Oka : Telomerase Activity and Nm23-H2 Protein Expression in Hepatocellular Carcinoma, Anticancer Research, Vol.23, No.1A, 43-47, 2003.
(要約)
Telomerase activity is up-regulated in most hepatocellular carcinomas (HCCs). Nm23-H2 has been shown to promote the expression of the c-myc gene, a candidate transcriptional activator of the human telomerase reverse transcriptase gene. Therefore, this study was undertaken to clarify the relationship between nm23-H2 expression and telomerase activity in HCCs. Telomerase activity and nm23-H2 protein expression in 24 HCCs were analyzed by telomeric repeat amplification protocol (TRAP) assay and immunohistochemistry, respectively. The incidence of positive telomerase activity was significantly higher in tumor tissues than in normal liver tissues (18 out of 24 vs. 7 out of 24, p = 0.0015), and nm23 -H2 protein was more abundantly expressed in tumors than in corresponding normal liver tissues. Tumor nm23-H2 immunoreactivity was associated positively with tumor telomerase activity (p = 0.0037). These results demonstrate that tumor nm23-H2 expression might be associated positively with telomerase activity in HCC and suggest the value of tumor nm23-H2 linked to telomerase activity as a therapeutic target for HCC.
We administered interleukin (IL)-2 with mitomycin C (MMC) and 5-fluorouracil (5-FU) by hepatic arterial infusion for the treatment of liver recurrence from colorectal cancer. The regimen consisted of continuous hepatic arterial infusion of IL-2 (7 x 10(5) JRU/day)/5-FU (250 mg/day) for 4 weeks. After those 4 weeks, a weekly hepatic arterial infusion of IL-2 (2.1 x 10(6) JRU)/5-FU (250 mg) was performed more than 4 weeks. MMC (4 mg) was given as a bolus weekly. This therapy resulted in partial response (PR) in one case, progressive disease (PD) in one case, and no change (NC) in one case. The toxicity of the therapy was a slight in all cases. We herein report 3 patients treated with hepatic arterial infusion of IL-2 with MMC and 5-FU for liver recurrence from colorectal cancer. This therapy may be a new strategy for metastatic colorectal cancer.
An autopsy case of sepsis following radiofrequency ablation (RFA) for metastatic liver carcinoma after bile duct reconstructive operation is reported. A 72-year-old man underwent pylorus-preserving pancreaticoduodenectomy and reconstruction with the Suzuki-method (PD-III) for extrahepatic bile duct cancer in October 1998. A metastatic lesion was recognized in the liver (S3) in November 2001. Percutaneous RFA was performed for a recurrent lesion. A metastatic lesion was recognized again in the same segment in February 2002. Percutaneous RFA was performed again on February 26 and March 12. The patient was discharged without hemorrhage, infection, or hepatic failure on March 22. He complained of general fatigue on March 26. He was diagnosed with liver abscess, sepsis, acute renal failure, and disseminated intravascular coagulation, and received intensive care, but died on April 1. The autopsy revealed liver necrotic abscess at the RFA locus and multiple microabscesses of the liver, heart, and kidney.
(キーワード)
Acute Kidney Injury / Aged / Bile Duct Neoplasms / Bile Ducts / Bile Ducts, Intrahepatic / Catheter Ablation / Disseminated Intravascular Coagulation / Humans / Liver Abscess / Liver Neoplasms / Male / Pancreaticoduodenectomy / Postoperative Complications / Sepsis
(文献検索サイトへのリンク)
● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 12484045
Chronic pancreatitis (CP) is frequently associated with stone formation within the pancreatic duct system. The mechanism of pancreatic stone formation, however, is still unclear.
Norio Iizuka, Masaaki Oka, Hisafumi Yamada-Okabe, Naohide Mori, Takao Tamesa, Toshimasa Okada, Norikazu Takemoto, Akira Tangoku, Kenji Hamada, Hironobu Nakayama, Takanobu Miyamoto, Shunji Uchimura and Yoshihiko Hamamoto : Comparison of gene expression profiles between hepatitis B virus- and hepatitis C virus-infected hepatocellular carcinoma by oligonucleotide microarray data on the basis of a supervised learning method., Cancer Research, Vol.62, No.14, 3939-3944, 2002.
(要約)
Gene expression profiles of hepatocellular carcinomas (HCCs) associated with hepatitis B virus (HBV) and hepatitis C virus (HCV) were analyzed and compared. Oligonucleotide microarrays containing >6000 genes and subsequent gene selection by a supervised learning method yielded 83 genes for which expression differed between the two types of HCCs. Expression levels of 31 of these 83 genes were increased in HBV-associated HCCs, and expression levels of the remaining 52 genes were increased in HCV-associated HCCs. The 31 genes up-regulated in HBV-associated HCC included imprinted genes (H19 and IGF2) and genes relating to signal transduction, transcription, and metastasis. The 52 genes up-regulated in HCV-associated HCC included a number of genes responsible for detoxification and immune response. These results suggest that HBV and HCV cause hepatocarcinogenesis by different mechanisms and provide novel tools for diagnosis and treatment of HBV- and HCV-associated HCCs.
N Yahara, T Abe, K Morita, Akira Tangoku and M Oka : Comparison of interleukin-6, interleukin-8, and granulocyte colony-stimulating factor production by the peritoneum in laparoscopic and open surgery., --- Human mesothelial cells secrete a variety of cytokines. The levels of postoperative serum inflammatory cytokines are thought to reflect the magnitude of surgical stress. ---, Surgical Endoscopy, Vol.16, No.11, 1615-1619, 2002.
(要約)
Human mesothelial cells secrete a variety of cytokines. The levels of postoperative serum inflammatory cytokines are thought to reflect the magnitude of surgical stress. Pieces of peritoneum were obtained immediately upon and 1 h after entry into the abdominal cavity in nine patients undergoing laparoscopic surgery and 11 patients undergoing open surgery. The samples were cultured and interleukin (IL)-6, IL-8, and granylocyte colony-stimulating factor (G-CSF) levels in the supernatants were measured by enzyme-linked immunosorbent assay (ELISA). Expression of IL-6, IL-8, and G-CSF mRNAs was examined by RT-PCR. At 1 h after laparotomy, the amounts of IL-6 and G-CSF produced by the peritoneum were significantly greater than those obtained immediately after the procedure, but this difference was not observed with laparoscopic surgery. Reverse transcription-polymerase chain reaction (RT-PCR), which showed an increase in the expression of cytokine mRNAs at 1 h after laparotomy, was compatible with these results. The lower levels of cytokine production by the peritoneum suggest that laparoscopic surgery is associated with lower degree of surgical stress.
Norio Iizuka, Shoichi Hazama, Kiyoshi Yoshimura, Shigefumi Yoshino, Akira Tangoku, Koji Miyamoto, Kiwamu Okita and Masaaki Oka : Anticachectic effects of the natural herb Coptidis rhizoma and berberine on mice bearing colon 26/clone 20 adenocarcinoma., International Journal of Cancer, Vol.99, No.2, 286-291, 2002.
(要約)
We previously showed that the natural herb Coptidis rhizoma has an anticachectic effect in nude mice bearing human esophageal cancer cells. We further investigated this phenomenon by examining the anticachectic effect of C. rhizoma in syngeneic mice bearing colon 26/clone 20 carcinoma cells, which cause IL-6-related cachexia after cell injection. We evaluated nutritional parameters such as serum glucose level and wasting of adipose tissue and muscle in tumor-bearing and non-tumor-bearing mice treated with C. rhizoma (CR) supplement or a normal diet. IL-6 levels in those mice were quantified by ELISA and real-time RT-PCR. CR supplementation significantly attenuated weight loss in tumor-bearing mice without changing food intake or tumor growth. Furthermore, these mice maintained good nutritional status. IL-6 mRNA levels in tumors and spleens and IL-6 protein levels in tumors and sera were significantly lower in tumor-bearing mice treated with CR supplement than in those treated with a normal diet. CR supplementation did not affect food intake, body weight, nutritional parameters and IL-6 levels in non-tumor-bearing mice. An in vitro study showed that C. rhizoma and its major component, berberine, inhibited IL-1-induced IL-6 mRNA expression in a dose-dependent manner in colon 26/clone 20 cells. Our results showed that C. rhizoma exerts an anticachectic effect on colon 26/clone 20-transplanted mice and that its effect is associated with tumor IL-6 production. We also suggest that its effect might be due to berberine.
Naofumi Takano, Norio Iizuka, Shoichi Hazama, Shigefumi Yoshino, Akira Tangoku and Masaaki Oka : Expression of estrogen receptor-alpha and -beta mRNAs in human gastric cancer., Cancer Letters, Vol.176, No.2, 129-135, 2002.
(要約)
To clarify the roles of estrogen receptors (ERs) in gastric cancers, we evaluated expression of ER-alpha and ER-beta mRNAs in 41 pairs of tumorous and non-tumorous tissues of gastric cancer patients and in six gastric cancer cell lines by reverse transcription-polymerase chain reaction method. ER-alpha and ER-beta mRNAs were detected in 21 (51%) and 30 (73%) of 41 tumors and in 15 (37%) and 36 (88%) of 41 corresponding normal tissues, respectively. There were no statistically significant associations between expression of ER-alpha and/or ER-beta mRNAs in tumors and clinicopathologic factors. Between the tumorous and normal tissues, expression of ER-alpha and ER-beta mRNAs were changed in 20 (49%) and unchanged in 21 (51%) of the 41 cases. The incidences of lymph node metastasis and liver metastasis were significantly higher in changed cases than in unchanged cases (P=0.031 and P=0.021, respectively). We confirmed that ER-alpha and ER-beta mRNA were expressed in 2 and 6 of the six gastric cancer cell lines, respectively. Together with this finding, our results indicate that ER-beta mRNAs are preferentially expressed in gastric cancers. Our data also suggest that altered expression of ER-alpha and ER-beta mRNAs in tumors compared with corresponding normal gastric tissues is related to increased metastatic potential in gastric cancers. Further studies are needed to clarify the role of ERs in gastric cancers.
Takashi Ueno, Akira Tangoku, Shigefumi Yoshino, Toshihiro Abe, Hiroaki Toshimitsu, Tomoko Furuya, Shigeto Kawauchi, Atsunori Oga, Masaaki Oka and Kohsuke Sasaki : Gain of 5p15 detected by comparative genomic hybridization as an independent marker of poor prognosis in patients with esophageal squamous cell carcinoma., Clinical Cancer Research, Vol.8, No.2, 526-533, 2002.
(要約)
Comparative genomic hybridization was applied to 51 primary esophageal squamous cell carcinomas (ESCCs) to clarify the relation between DNA sequence copy number aberrations (DSCNAs) and the clinicopathology of the disease. The average number of DSCNAs was 10.9 DSCNAs/tumor (6.1 gains and 4.9 losses), ranging from 1-30 DSCNAs/tumor. Gain of 3q26-qter and loss of 18q22-qter were detected in >60% of stage I tumors and considered to play an important role in the development of ESCC. Whereas gain of 8q24-qter was observed in 82.6% (19 of 23) of stage III and IV cancers, it was seen in 27.3% (3 of 11) of stage I tumors. It is suggested that gain of 8q24-qter plays an important role in tumor progression. Gains of 8q24-qter and 20q12-qter and loss of 11q22-23 were linked to nodal metastasis (P = 0.0006, 0.002, and 0.02, respectively). Gains of 5p15 and 14q21 were associated with distant organ metastasis after surgery (P = 0.006 and 0.02, respectively). These observations suggest that nodal and distant organ metastases involve different genes. Gains of 5p15, 8q24-qter, and 14q21 were significantly associated with unfavorable prognosis (P = 0.0002, 0.007, and 0.04, respectively). Multivariate analysis revealed the 5p15 gain to be an independent prognostic marker with a higher significance than that of nodal status (risk ratio = 5.95; P = 0.001). The present findings indicate that comparative genomic hybridization analysis may be used to predict the likelihood of a poor or favorable outcome in cases of ESCC.
A 55-year-old female patient was diagnosed with right breast cancer with brain metastasis of 3 cm in size. Neurological examination revealed paralysis in the left upper and lower extremities. Chemotherapy and hormone therapy were performed. Brachytherapy by Cyberknife was performed for the brain metastatic lesion. As a result, the brain metastatic lesion decreased in size to 1 cm on the CT-scan after 2 months. The paralysis disappeared and the patient's QOL improved. Cyberknife therapy was useful for a brain metastatic lesion that harmed the patient's QOL.
(キーワード)
Antineoplastic Combined Chemotherapy Protocols / Brain Neoplasms / Breast Neoplasms / Carcinoma, Ductal, Breast / Female / Humans / Lymphatic Metastasis / Middle Aged / Paclitaxel / Quality of Life / Radiosurgery / Tamoxifen / Taxoids
(文献検索サイトへのリンク)
● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 11708034
M Ariga, K Suga, N Matsunaga, K Sasai, K Shimizu, Y Ishikawa, Akira Tangoku and R Eto : Failure to detect a huge Meckel's diverticulum with abundant ectopic gastric mucosa on gastric mucosal scintigraphy with Tc-99m pertechnetate., Clinical Nuclear Medicine, Vol.26, No.5, 470-471, 2001.
T Abe, M Oka, Akira Tangoku, H Hayashi, K Yamamoto, N Yahara, K Morita, T Tabata and Y Ohmoto : Interleukin-6 production in lung tissue after transthoracic esophagectomy., Journal of the American College of Surgeons, Vol.192, No.3, 322-329, 2001.
(要約)
The mechanisms of the reported high increase in interleukin-6 (IL-6) levels after esophagectomy are unclear. We investigated the influence of an intrathoracic procedure, esophagectomy, on IL-6 production in lung tissue.
N lizuka, K Miyamoto, Akira Tangoku, H Hayashi, S Hazama, S Yoshino, K Yoshimura, K Hirose, H Yoshida and M Oka : Downregulation of intracellular nm23-H1 prevents cisplatin-induced DNA damage in oesophageal cancer cells: possible association with Na(+), K(+)-ATPase., British Journal of Cancer, Vol.83, No.9, 1209-1215, 2000.
(要約)
Previously, we showed that expression of nm23-H1 is associated inversely with sensitivity to cisplatin in human oesophageal squamous cell carcinoma (OSCC). The present study was undertaken to investigate the association of nm23-H1 expression with cisplatin-induced DNA damage in OSCC using antisense nm23-H1 transfectants. YES-2/AS-12, an antisense nm23-H1-transfected OSCC cell line, showed significantly reduced expression of intracellular nm23-H1 protein compared with that in parental YES-2 cells and YES-2/Neo transfectants. Surface expression of nm23-H1 protein was not observed in any of the three cell lines. PCR analysis for DNA damage demonstrated that YES-2/AS-12 cells were more resistant to nuclear and mitochondrial DNA damage by cisplatin than were YES-2/Neo cells. In addition, mitochondrial membrane potentials and DNA fragmentation assays confirmed that YES-2/AS-12 was more resistant than YES-2/Neo to apoptosis induced by cisplatin. In contrast, YES-2/AS-12 was more sensitive to ouabain, a selective inhibitor of Na(+), K(+)-ATPase, than YES-2 and YES-2/Neo. Pre-treatment with ouabain resulted in no differences in cisplatin sensitivity between the three cell lines examined. Intracellular platinum level in YES-2/AS-12 was significantly lower than that in YES-2 and YES-2/Neo following incubation with cisplatin, whereas ouabain pre-treatment resulted in no differences in intracellular platinum accumulations between the three cell lines. Our data support the conclusion that reduced expression of intracellular nm23-H1 in OSCC cells is associated with cisplatin resistance via the prevention of both nuclear and mitochondrial DNA damage and suggest that it may be related to Na(+), K(+)-ATPase activity, which is responsible for intracellular cisplatin accumulation.
S Yoshino, T Tabata, S Hazama, N Iizuka, K Yamamoto, M Hirayama, Akira Tangoku and M Oka : Immunoregulatory effects of the antitumor polysaccharide lentinan on Th1/Th2 balance in patients with digestive cancers., Anticancer Research, Vol.20, No.6C, 4707-4711, 2000.
(要約)
Recent studies demonstrated that patients with advanced cancer may have impaired cell-mediated immunity caused by an imbalance between Th1 and Th2 responses. We evaluated the ability of lentinan (LNT) to modulate Th1 and Th2 responses in patients with digestive cancers.
Continuous systemic infusion of low-dose cisplatin (CDDP) (10 mg/body/day) and 5-fluorouracil (5-FU) (500 mg/body/day) was performed for advanced hepatocellular carcinoma (HCC) after hepatectomy with diffuse lung metastases and multiple intrahepatic metastases. This infusion chemotherapy, cisplatin was continued for five days, and discontinued for two days, whereas 5-fluorouracil was administered every day and repeated four weeks as one course basally. Remnant metastases had almost disappeared after systemic chemotherapy for 10 weeks. In our experience, the response rate in 13 patients who underwent reduction surgery for multiple HCC was 84.6%. Continuous infusion of low-dose CDDP/5-FU may be effective in patients having absolute non-curative resection.
A 39-year-old woman was admitted to our hospital because of advanced hepatocellular carcinoma. She had good liver function with clinical Stage I. Abdominal ultrasonographic study and CT scan revealed a huge tumor of 12 cm in diameter in the left lobe of the liver, with tumor thrombi in the portal and hepatic veins. A chest CT scan demonstrated multiple bilateral lung metastases from 5 to 10 mm in size. An extended left hemihepatectomy with extirpation of the portal and hepatic venous tumor thrombi was performed. On postoperative day 7, low-dose cisplatin (10 mg/day-5 days/week) and 5-fluorouracil (250 mg/day-continuous for 7 days/week) were administered intravenously. Four weeks after chemotherapy, CT scan revealed no recurrence in the liver and no change in the lung metastases. The patient is now being treated on an outpatient basis with no change in the metastatic tumors.
N Mori, M Oka, S Hazama, N Iizuka, K Yamamoto, S Yoshino, Akira Tangoku, Takafumi Noma and K Hirose : Detection of telomerase activity in peritoneal lavage fluid from patients with gastric cancer using immunomagnetic beads, British Journal of Cancer, Vol.83, No.8, 1026-1032, 2000.
(要約)
Cytologic examination of peritoneal lavage fluid is a useful predictor of peritoneal recurrence in gastric cancer. However, this technique is not overly sensitive and requires special abilities in the cytologist. In this study, telomerase activity was used to detect free cancer cells in peritoneal lavage fluid from patients with gastric cancer. In the first part, 12 lavage-fluid samples obtained from 12 patients with gastric cancer were analysed using the conventional telomeric repeat amplification protocol (TRAP) assay. Three of five patients with early gastric cancer had positive telomerase activity. These false-positive results may have been due to lymphocyte contamination. Furthermore, polymerase chain reaction inhibitors were also detected in the lavage-fluid samples. Therefore, we developed a novel method for elimination of haematopoietic cell and Taq polymerase inhibitors to increase the accuracy of the TRAP assay using immunomagnetic beads, which bind to most normal and neoplastic human epithelial cells. Telomerase activity was found in 10 of 20 (50%) lavage-fluid samples from patients with serosal or subserosal invasion. Cytologic examination was positive in nine of 20 (45%) samples. Both the telomerase activity and cytology were negative in all 14 patients without serosal or subserosal invasion. These results suggest that the TRAP assay combined with immunomagnetic beads might be useful for detection of free cancer cells in the peritoneal space in gastric cancer without the aid of an experienced cytologist.
N Iizuka, K Miyamoto, S Hazama, S Yoshino, K Yoshimura, K Okita, T Fukumoto, S Yamamoto, Akira Tangoku and M Oka : Anticachectic effects of Coptidis rhizoma, an anti-inflammatory herb, on esophageal cancer cells that produce interleukin 6., Cancer Letters, Vol.158, No.1, 35-41, 2000.
(要約)
Herbs as alternative cancer therapies have attracted a great deal of recent attention due to their low toxicity and costs. In this study, the antitumor activity and anticachectic effect of Coptidis rhizoma, an anti-inflammatory herb, were investigated in nude mice carrying a human esophageal cancer cell line YES-2, which constitutively secretes interleukin-6 (IL-6) and induces cachexia when injected into these mice. In this study, in vivo growth of YES-2 cells was not affected by an oral supplement containing the extract powder of C. rhizoma at a final concentration of 1% (CR supplement). However, in comparison with normal diet, CR supplement significantly attenuated weight loss of tumor-bearing mice without a change in food or water intake. Tumor IL-6 levels were significantly lower in mice treated with CR supplement than in control mice (P<0.001). Serum IL-6 was detectable in four (50%) of eight control mice; IL-6 was not detected in mice treated with CR supplement. We also confirmed that berberine (8-32 microM), a major component of C. rhizoma, dose-dependently inhibited secretion of IL-6 by YES-2 cells in vitro. Moreover, reverse transcription-PCR assay showed that treatment of YES-2 cells with berberine (8-32 microM) for 24 h reduced IL-6 mRNA expression. Our results suggest that C. rhizoma may have an anticachectic effect on esophageal cancer and an effect is associated with the ability of berberine to down-regulate tumor IL-6 production.
Esophageal dilation therapy for esophageal achalasia has a 300-year history and remains the first-line therapy because of its low cost, progressively decreasing morbidity and mortality, and possibility of surgery for patients who do not improve. Another advantage is the feasibility of repeated trial even after surgery. The aim of this procedure is to produce a controlled tear in the lower esophageal sphincter muscle. Precise esophagographic, endoscopic, and manometric diagnosis is necessary for successful esophageal dilation therapy. In addition, the exclusion of pseudoachalasia using echogram or CT scan is important. The procedure should be carried out accurately to prevent complications. If perforation occurs, appropriate, timely management is required.
Akira Tangoku, H Hayashi, S Kanamura, S Yoshino, T Abe, Y Yoshimoto, T Morioka and M Oka : Lymph node metastases identified with mediastinoscopy in a patient with superficial carcinoma of the esophagus., Surgical Endoscopy, Vol.14, No.6, 595, 2000.
(要約)
Superficial esophageal cancers limited to the lamina propria are not associated with lymph node metastases. Mediastinoscopic transhiatal esophagectomy was planned in a patient with widespread superficial cancer of the midthoracic esophagus. Sampling of the upper mediastinal lymph nodes revealed metastases. The operation was converted to a transthoracic esophagectomy with radical lymphadenectomy. Histopathologic examination of the resection specimen showed three metastatic lymph nodes, despite local invasion limited to the lamina propria. This is the first report of a patient with superficial esophageal cancer and lymph node metastases.
K Tada, M Oka, H Hayashi, Akira Tangoku, A Oga and K Sasaki : Cytogenetic analysis of esophageal squamous cell carcinoma cell lines by comparative genomic hybridization: relationship of cytogenetic aberrations to in vitro cell growth., Cancer Genetics and Cytogenetics, Vol.117, No.2, 108-112, 2000.
(要約)
Cancer is characterized by autonomous growth of cells, and it is widely accepted that cell proliferation is primarily influenced by individual cell genetics. To elucidate the mechanisms of cancer cell proliferation, we studied differences in genetic aberrations for different type of tumors with different proliferation characteristics. We employed comparative genomic hybridization (CGH) to detect genetic aberrations in six cell lines of esophageal squamous cell carcinoma (ESCC). Three cell lines (YES-1, -2, and -3) grow in culture without fetal calf serum (group A), while others require serum to be maintained in vitro (group B). Both groups showed very similar cytogenetic aberrations: over-representations of 11q13 (6/6), 8q23-qter (5/6), Xq25-qter (5/6), 3q26-qter (4/6), 5p (4/6), 7p15-pter (4/6), 8q21.3-q22 (4/6), 17p (4/6), and 20q13 (4/6), and under-representations of 18q21-qter (6/6), 4q28-q33 (4/6), and 9p21 (4/6). Six amplification loci were mapped to chromosomal regions of 6q23 (1 case), 7p12 (2 cases), 9p21 (1 case), 11p11.2-12 (3 cases), 11q13 (2 cases), and 17p12 (2 cases). However, some differences were detected. DNA copy number increases at 7p12-p13, 11q14-q22, and 11q22-qter and under-representations of 4p, 8p, and 11p14-pter. In contrast, gains at 12p and 20p, and losses at 3p and 5q were detected only in group-B cell lines. These observations suggest that cytogenetic differences between the two groups may be linked to differences in cell growth characteristics in vitro, and that the genes in these chromosomal regions may play important roles in cell proliferation.
K Tada, M Oka, Akira Tangoku, H Hayashi, A Oga and K Sasaki : Gains of 8q23-qter and 20q and loss of 11q22-qter in esophageal squamous cell carcinoma associated with lymph node metastasis., Cancer, Vol.88, No.2, 268-273, 2000.
(要約)
Esophageal squamous cell carcinoma (ESCC) is associated with poor prognosis and lymph node metastasis is one of the critical prognostic factors. Although it is important to elucidate the genetic aberrations underlying its lymph node metastasis, to the authors' knowledge little is known regarding alterations in the primary ESCC that are linked with ESCC metastasis to the lymph nodes.
N Iizuka, K Miyamoto, K Okita, Akira Tangoku, H Hayashi, S Yosino, T Abe, T Morioka, S Hazama and M Oka : Inhibitory effect of Coptidis Rhizoma and berberine on the proliferation of human esophageal cancer cell lines., Cancer Letters, Vol.148, No.1, 19-25, 2000.
(要約)
Our previous study demonstrated that the herbal medicine, Oren-to, had antitumor effects on esophageal cancer cells (ECCs) in vitro. The purpose of this study was to examine which of the seven constituents of Oren-to had antitumor effects on esophageal cancer cells. MTT assay showed that, of the seven constituents, only the aqueous extract of Coptidis Rhizoma had potent inhibitory effect on the proliferation of two types of ECC lines, YES-3 and YES-4. In addition, the proliferation of all six types of ECC lines (YES-1 to YES-6) was inhibited in a dose-dependent manner (P<0.001 for all), when co-cultured at each concentration of Coptidis Rhizoma for 72 h. The ID50 of Coptidis Rhizoma for YES-1 to YES-6 was 2.2 microg/ml, 3.0 microg/ml, 0.25 microg/ml, 2.8 microg/ml, 2.5 microg/ml, and 0.5 microg/ml, respectively, berberine, one of protoberberine components of Coptidis Rhizoma, showed potent antitumor effects on all six types of ECC lines as well as Coptidis Rhizoma. In addition, the ID50 of berberine showed a positive correlation with that of Coptidis Rhizoma in six types of ECC lines examined (r2 = 0.763, P = 0.023). Cell cycle analysis of Coptidis Rhizoma-treated cancer cells showed the accumulation of cells in the G0/G1 phase and relative decrease of the S phase. These results support the possibility that the use of Coptidis Rhizoma containing abundant berberine may be useful as one of alternative therapies for esophageal cancers.
T Abe, Akira Tangoku, H Hayashi, S Takeda, S Yoshino and M Oka : Esophageal perforation and mediastinal abscess following placement of a covered self-expanding metallic stent and radiation therapy in a cancer patient., Surgical Endoscopy, Vol.13, No.10, 1044-1046, 1999.
(要約)
Patients with advanced esophageal cancer may require intubation with a stent to relieve debilitating dysphagia. However, if these patients also undergo radiation therapy, they may incur esophageal injury, thus increasing the risk of perforation after placement of the stent. Herein we report the case of a 71-year-old man who received such combination therapy and died of severe sepsis 65 days after the stent was inserted. An autopsy revealed that the stent had perforated into the mediastinal pleura and that an abscess had developed around the perforation. We conclude that caution should be taken before combining radiation therapy with the use of a stent.
Akira Tangoku, K Yamamoto, K Hirazawa, T Takao, N Mori, K Tada and M Oka : Laparoscopic resection of large leiomyomas of the gastric fundus., Surgical Endoscopy, Vol.13, No.10, 1050-1052, 1999.
(要約)
Two patients with a large leiomyoma arising from the gastric fundus underwent laparoscopic resection. In case 1, the tumor was located in the anterior wall of the gastric fundus. To prevent stenosis and preserve the volume of the residual stomach, intragastric resection was adopted. The tumor was markedly and resected with laparosonic coagulating shears with a 1-cm safety margin. In case 2, a large tumor was detected in the duodenal bulb. Serious hemorrhage mandated emergency resection. The tumor originated from the posterior wall of the fundus. Attempts at reduction with the forceps failed. Reduction by digital manipulation via laparoscopic port sites was successful. An endostapler was used to resect the tumor and close the anterior wall. Both patients recovered uneventfully.
Seven patients with postoperative recurrence of hepatocellular carcinoma (HCC) and four patients who underwent absolute non curative resection for HCC were treated with continuous arterial infusion of low-dose cisplatin (CDDP) (10 mg/body/day) and 5-fluorouracil (5-FU) (250 mg/body/day). This infusion chemotherapy was continued for five days and discontinued for two days, repeated over four weeks as one course. The response rate in patients with postoperative recurrence was 42.9%, while that in patients who underwent reduction surgery for multiple HCC was 75%. Continuous arterial infusion of low-dose CDDP/5-FU may be effective in patients with multiple small intrahepatic metastases.
Docetaxel is an excellent agent with a high antitumor effect for the treatment of advanced/recurrent breast cancer. A 55-year-old female with metastatic liver tumors from breast cancer showed a remarkable response to intra-arterial administration of docetaxel (20 mg/week, or 40 mg/2 weeks). Since CT and MRI imaging revealed multiple metastases in the liver, intra-arterial chemotherapy was selected. No critical side effect was found during this chemotherapy. A CT scan 3 months after chemotherapy showed a partial response. We conclude that this intra-arterial chemotherapy using docetaxel will be safe and useful for liver metastases from breast cancer.
N Iizuka, K Hirose, Takafumi Noma, S Hazama, Akira Tangoku, H Hayashi, T Abe, K Yamamoto and M Oka : The nm23-H1 gene as a predictor of sensitivity to chemotherapeutic agents in oesophageal squamous cell carcinoma, British Journal of Cancer, Vol.81, No.3, 469-475, 1999.
(要約)
Recently, nm23-H1, an anti-metastasis gene, has been reported to correlate with sensitivity to chemotherapeutic agents including cisplatin in human breast and ovarian carcinoma cells. The aim of this study was to evaluate a role for nm23-H1 in responsiveness to cisplatin-based chemotherapy in patients with oesophageal squamous cell carcinoma (OSCC). The expression of nm23-H1 protein was examined immunohistochemically in 32 eligible patients with OSCC who underwent adjuvant chemotherapy with cisplatin, etoposide, and 5-fluorouracil after tumour resection. Fifteen (46.9%) of 32 patients were positive for nm23-H1 staining and 17 (53.1%) were negative. Both disease-free survival and overall survival rates of nm23-H1-negative patients were significantly shorter than in nm23-H1-positive patients (P < 0.01 for both). There was no significant difference in clinicopathologic characteristics between nm23-H1-positive and nm23-H1-negative groups. Multivariate analysis also showed that nm23-H1 expression was the most significant factor for overall survival of OSCC patients included in this study (P = 0.0007). To further study the role of nm23-H1, a human OSCC cell line (YES-2) was transfected with a plasmid containing a fragment of the nm23-H1 cDNA in an antisense orientation. Reduced expression of nm23-H1 protein in the antisense-transfected (AS) clones was found by Western blot analysis as compared to wild-type YES-2 and YES-2/Neo (clone transfected with the neomycin resistance gene alone). MTT (3-(4,5-dimethyl-2-thiazol)-2,5-diphenyl-2H tetrazolium bromide) assay showed that reduced expression of the nm23-H1 protein in AS clones was consistent with the degree of increased resistance to cisplatin but not etoposide or 5-fluorouracil. These data support the conclusion that reduced expression of nm23-H1 may be associated with resistance to cisplatin, suggesting the value of nm23-H1 expression as a prognostic marker for OSCC patients who are to undergo cisplatin-based chemotherapy.
Akira Tangoku, H Hayashi, S Yoshino, T Ueno, T Abe, Y Yoshimoto, T Morioka and M Oka : Wire-guided transoral esophagogastrostomy for carcinoma of the cervical esophagus., Journal of the American College of Surgeons, Vol.189, No.3, 330-333, 1999.
N Iizuka, S Hazama, K Hirose, T Abe, N Tokuda, T Fukumoto, Akira Tangoku and M Oka : Interleukin-1 receptor antagonist mRNA expression and the progression of gastric carcinoma., Cancer Letters, Vol.142, No.2, 179-184, 1999.
(要約)
Interleukin-1 receptor antagonist (IL-1ra), an endogeneous inhibitor of IL-1, plays an immunosuppressive role in vivo by blocking the proinflammatory effects of IL-1. In the present study, we examined whether IL-1ra expression in human gastric carcinoma correlates with tumor progression and/or metastatic potential. The reverse transcription-polymerase chain reaction was used to compare the expression of the secreted form of IL-1ra (sIL-1ra) and the intracellular form of IL-1ra (icIL-1ra) mRNA in tumor and corresponding benign tissue obtained from 38 patients with gastric carcinoma. The incidence of sIL-1ra mRNA expression was significantly higher in tumor (52%) than in corresponding benign tissue (18%) (P = 0.002). On the contrary, icIL-1ra mRNA was detected in all tumors and benign tissues. The expression of sIL-1ra mRNA by malignant tissue correlated positively with both lymph node metastasis (P = 0.008) and liver metastasis (P = 0.015). There was no association between tumor sIL-lra mRNA expression and other clinicopathologic factors. The degree of regional lymph node reaction, such as sinus histiocytosis, in tumors expressing sI-1ra mRNA was significantly weaker than that in tumors without sIL-1ra mRNA expression (5/20 vs. 12/18, P = 0.010). These results demonstrate that the altered expression of sIL-1ra by malignant tissue may be related to the progression of gastric carcinoma via modulating host immune response.
Y Masaki, M Oka, Y Ogura, T Ueno, K Nishihara, Akira Tangoku, M Takahashi, M Yamamoto and T Irimura : Sialylated MUC1 mucin expression in normal pancreas, benign pancreatic lesions, and pancreatic ductal adenocarcinoma., Hepato-Gastroenterology, Vol.46, No.28, 2240-2245, 1999.
(要約)
Pancreatic cancer has the poorest prognosis of all gastrointestinal cancers. Because sialylated mucin influences the biologic behavior of carcinoma cells, we investigated sialylated MUC1 mucin expression in patients with pancreatic ductal adenocarcinoma.
M Oka, S Hazama, M Takahashi, K Yamamoto, T Abe, S Yoshino, H Hayashi and Akira Tangoku : Relationship between serum levels of soluble interleukin-2 receptor and various disease parameters in patients with squamous cell carcinoma of the esophagus., Hepato-Gastroenterology, Vol.46, No.28, 2254-2259, 1999.
(要約)
Soluble interleukin-2 receptor (sIL-2R) is a useful biomarker for the management of hematologic malignancies. We determined the significance of serum sIL-2R levels in patients with squamous cell carcinoma of the esophagus.
A 44-year-old woman complained of headache and palpitation. Magnetic resonance imaging showed bilateral adrenal tumors 10 x 9 cm in size on the left side and 8 x 4 cm in size on the right side. CT scan revealed a 0.7 x 0.7 cm mass in the thyroid. Hormonal examinations showed high values of urinary cathecholamines and serum calcitonin. DNA sequence analysis of peripheral white blood cells revealed that codon 634 in exon 11 of the RET gene was mutated from TGC (Cys) to TAC (Tyr). From these findings, a diagnosis was made of MEN2A with bilateral adrenal pheochromocytomas and medullary thyroid carcinoma. Bilateral adrenalectomy and thyroidectomy were performed. The same mutation of the RET gene was detected in all her 3 children, in two of whom, early stage medullary thyroid carcinoma was detected and thyroidectomy was performed. DNA analysis of the RET gene was useful for the diagnosis of carriers of MEN2A and the early detection of medullary thyroid carcinoma.
M Oka, Y Yoshimoto, T Ueno, K Yoshimura, Y Maeda and Akira Tangoku : Treatment of cholecystoduodenal fistula by laparoscopy., Surgical Laparoscopy, Endoscopy & Percutaneous Techniques, Vol.9, No.3, 213-216, 1999.
(要約)
We describe a patient with cholecystoduodenal fistula treated by a laparoscopic approach. Use of a flexible videoscope, flexible retractor, and endoscopic transecting stapler allows for laparoscopic treatment of cholecystoenteric fistulae.
K Suga, K Miura, N Kume, A Hara, N Matsunaga, Akira Tangoku and M Oka : Tc-99m colloid and Ga-67 imaging of splenic inflammatory pseudotumor correlation with ultrasound, CT, and MRI., Clinical Nuclear Medicine, Vol.24, No.5, 334-337, 1999.
(要約)
Splenic inflammatory pseudotumor is extremely rare and may mimic splenic neoplasms, such as lymphomas or hamartomas, clinically and radiologically. A case of a surgically proved splenic inflammatory pseudotumor is presented in which Tc-99m colloid SPECT and Ga-67 scintigraphy characterized the changes in the spleen, but the findings of ultrasound and unenhanced CT and MRI were nonspecific. This report indicates the utility of radionuclide imaging for diagnosing splenic inflammatory pseudotumor.
N Iizuka, Akira Tangoku, H Hayashi, S Yosino, T Abe, T Morioka and M Oka : The association between nm23-H1 expression and survival in patients with esophageal squamous cell carcinoma., Cancer Letters, Vol.138, No.1-2, 139-144, 1999.
(要約)
The nm23 gene is a potential metastasis suppressor gene originally identified using a murine melanoma cell line. The expression of nm23-H1 protein was examined immunohistochemically in 50 eligible patients with esophageal squamous cell carcinoma (ESCC). The expression was not correlated with other prognostic factors including lymph node metastases; however, overall survival rates of nm23-H1-negative patients were significantly shorter than those of nm23-H1-positive patients (P < 0.05). Furthermore, reduced expression of nm23-H1 was associated with shorter overall survival in patients with involved lymph nodes (P < 0.01), but not in patients without involved lymph nodes. These data support the conclusion that reduced expression of nm23-H1 may be associated with poor prognosis of ESCC patients, suggesting the value of nm23-H1 expression as a prognostic marker for ESCC patients, especially ESCC patients with involved lymph nodes.
T Takao, M Nishida, Y Maeda, S Hiraki, K Takao, Akira Tangoku and M Oka : Effect of cautery with irrigation forceps on the remnant liver after hepatectomy in rats., European Surgical Research, Vol.31, No.2, 173-179, 1999.
(要約)
Monopolar cautery with irrigation forceps (CIF) was devised for use in liver resection that does not require occlusion of inflow to the remnant liver. However, a high power output is required to divide the hepatic parenchyma which boils the irrigation water. This study was performed to investigate the effects of using CIF on the hepatic parenchyma. Histologic and biochemical examination was performed in rats which had undergone hepatectomy using the CIF, irrigating bipolar (IB), Pringle's maneuver with blunt dissection (group P), or a sham operation. A greater cautery distance was obtained with the CIF than the IB. There was no significant difference in the remnant liver function after the 1st postoperative day in any of the groups. CIF is an effective instrument for anatomic or nonanatomic hepatic resection.
Portal thrombectomy with extended hepatectomy for extensively progressive primary liver cancer (Vp 3), in which the tumor thrombus has spread beyond the first portal branches, will make other non-surgical treatments possible and improve patients quality of life. We have performed extensive resections in 15 cases of such Vp 3 liver cancer. One patient with huge HCC involving retrohepatic IVC underwent in situ extended left hepatectomy without reconstruction of IVC, resulting in postoperative renal failure because of thrombosis in the bilateral renal veins, but 14 other patients' postoperative courses were uneventful. Ten of 14 patients relapsed within one year, but these patients underwent non-surgical treatments, resulting in improvement in the quality of life. The 1-, and 3-year survival rates were 55.6% and 32.5%, respectively.
M Oka, K Yamamoto, M Nakamura, M Miyahara, T Ueno, K Nishihara and Akira Tangoku : Reconstruction after proximal gastrectomy using a stapled, U-shaped jejunal pouch., Journal of the American College of Surgeons, Vol.186, No.5, 601-603, 1998.
M Nakamura, Akira Tangoku, H Kusanagi, M Oka and T Suzuki : Breast cancer associated with Recklinghausen's disease: report of a case., Archiv für Japanische Chirurgie, Vol.67, No.1, 3-9, 1998.
(要約)
A 49-year-old woman with Recklinghausen's disease presented to our department for investigation of a left breast lump, measuring 60 mm x 50 mm, which she had first noticed 6 months earlier, but had disregarded, believing it to be another manifestation of her Recklinghausen's disease. The lump was suspected to be malignant based on physical examination and ultrasonography. Biopsy and frozen sections subsequently confirmed a diagnosis of scirrhous carcinoma. A standard radical mastectomy was performed, followed by postoperative chemoendocrine therapy. However, lungs, liver, and bone metastasis, as well as a contralateral breast tumor, developed and she died 4 months after surgery.
M Nakamura, Akira Tangoku, M Oka and T Suzuki : A case of invasive lobular carcinoma of the breast., The Kurume Medical Journal, Vol.45, No.1, 147-150, 1998.
(要約)
A 43-year-old woman presented to our department with left breast lump, measuring 10 mm x 10mm x 6mm. On physical examination and mammography, the lump was suspected to be due to mastopathy, but malignancy could not be excluded based on ultrasonography. Excisional biopsy showed that it was an invasive lobular carcinoma. A modified radical mastectomy was performed after obtaining informed consent. She remained disease-free seven years after surgery.
K Yamamoto, M Oka, H Hayashi, Akira Tangoku, T Gondo and T Suzuki : CYFRA 21-1 is a useful marker for esophageal squamous cell carcinoma., Cancer, Vol.79, No.9, 1647-1655, 1997.
(要約)
CYFRA 21-1 measures soluble cytokeratin-19 fragments in serum and is a useful marker for lung carcinoma, especially squamous cell carcinoma (SCC). The authors conducted this study to determine the significance of CYFRA 21-1 in patients with esophageal SCC.
K Suga, K Nishigauchi, K Shimizu, N Kume, N Matsunaga, Y Sato, Akira Tangoku, N Kouichi and K Esato : SPECT with In-111 autologous platelets to detect residual splenic tissue in two patients with relapsed thrombocytopenia., Clinical Nuclear Medicine, Vol.22, No.3, 141-146, 1997.
(要約)
In two patients with relapsed thrombocytopenia, the authors used SPECT with In-111 labeled autologous platelets to identify residual splenic tissue after splenectomy. One case involved a previously splenectomized patient with idiopathic portal hypertension, while the other had relapsed chronic idiopathic thrombocytopenic purpura (ITP). In both patients, SPECT showed a higher In-111 uptake in the splenic tissues compared with planar images. In the patient with ITP, a small accessory spleen had been overlooked on abdominal CT because of post-operative changes, but it was identified by superimposition of SPECT/CT images. These cases indicate that In-111 platelet SPECT is useful in detecting and localizing residual accessory splenic tissue associated with relapsed thrombocytopenia.
F Numa, H Ogata, Y Suminami, N Tsunaga, Y Nakamura, H Tamura, N Takasugi, H Kato, Akira Tangoku, T Uchiyama, M Oka, T Suzuki, M Yamamoto and K Naito : Pelvic exenteration for the treatment of gynecological malignancies., Archives of Gynecology and Obstetrics, Vol.259, No.3, 133-138, 1997.
(要約)
Twenty-three patients undergoing pelvic exenteration for primary and recurrent gynecological malignancies from 1976 to 1994 are reported. Fifteen patients underwent total pelvic exenteration, 3 underwent anterior exenteration, and 5 underwent a posterior procedure. Eight patients had exenteration as their primary treatment (primary group), and 15 underwent exenteration as secondary treatment (recurrent group). In the primary group, two patients developed recurrence and died of it at 6 and 20 months after operation. Five patients are still being followed up and are alive without disease. Four of these 5 patients have survived more than 5 years. In the recurrent group, 12 patients were followed up and three died of complications during the early years. Seven patients died of cancer with the mean survival time of 16.6 months. The mean age, average operating time, and mean blood loss in the primary and recurrent groups were 57 vs. 53 years, 8 hours and 20 min vs. 8 hours and 10 min, and 4,120 vs. 4,190 ml, respectively. The overall cumulative 5-year survival rate was 34.7%, being 68.6% in the primary group and 16.7% in the recurrent group. It is noteworthy that the 5-year survival rate was 51.3% in the patients who had surgical margins free of disease. In conclusion, pelvic exenteration should be considered an acceptable therapeutic option when appropriately selected.
M Oka, K Yamamoto, M Takahashi, M Hakozaki, T Abe, N Iizuka, S Hazama, K Hirazawa, H Hayashi, Akira Tangoku, K Hirose, T Ishihara and T Suzuki : Relationship between serum levels of interleukin 6, various disease parameters and malnutrition in patients with esophageal squamous cell carcinoma., Cancer Research, Vol.56, No.12, 2776-2780, 1996.
(要約)
Serum levels of interleukin 6 (IL-6) are correlated with the disease status and prognosis in cancer patients. IL-6 is also an important mediator of experimental cancer cachexia. We investigated the production of IL-6 and IL-6 receptors and expression of IL-6 mRNA by esophageal squamous carcinoma cells using immunohistochemical staining and in situ reverse transcription-PCR. We also measured levels of serum IL-6 using an ELISA in 50 patients with esophageal squamous cell carcinoma (ESCC) to determine the correlation between serum levels of IL-6 and clinicopathological factors IL-6 mRNA was expressed in the primary tumor. Esophageal squamous carcinoma cells produced both IL-6 and IL-6 receptor. IL-6 concentrations were significantly higher in the primary tumor than in the normal epithelium. The incidences of weight loss, tumor invasion to adjacent organs, and noncurative resection were significantly higher in ESCC patients with serum levels of IL-6 > or = 7 pg/ml (n = 13, group C) compared with patients with serum levels <7 pg/ml and > or = 3 pg/ml (n = 14, group B) and <3 pg/ml (n = 23, group A). Tumor size and C-reactive protein levels were significantly higher and albumin levels were significantly lower in group C. Results suggest that IL-6, which is produced by tumor cells, may be related to various disease parameters as well as to the nutritional status in patients with ESCC.
(キーワード)
Adult / Aged / Aged, 80 and over / Antigens, CD / Base Sequence / Carcinoma, Squamous Cell / Esophageal Neoplasms / Female / Humans / Interleukin-6 / Male / Middle Aged / Molecular Sequence Data / Neoplasm Proteins / Nutrition Disorders / RNA, Messenger / Receptors, Interleukin / Receptors, Interleukin-6 / Tumor Markers, Biological
(文献検索サイトへのリンク)
● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 8665513
P Chowdhury, R Doi, Akira Tangoku and P L. Rayford : Structural and functional changes of rat exocrine pancreas exposed to nicotine., The International Journal of Pancreatology, Vol.18, No.3, 257-264, 1995.
(要約)
Nicotine, an addictive agent in cigarette smoking, has been implicated in the etiology of pancreatitis and pancreatic carcinoma. Very little experimental data are, however, available regarding the effects of nicotine on the structural and functional changes in the exocrine pancreas. Two groups of rats divided into control and nicotine exposed were used. The animals in the nicotine group were maintained for 28 d with ad libitum water containing 0.77 mM of nicotine. At term, the animals were sacrificed, and pancreas was examined for pathological and functional changes. Nicotine induced cytoplasmic vacuolation and cellular edema in the exocrine pancreas. Plasma levels of glucose and insulin and CCK-8-stimulated amylase release in isolated acini were significantly decreased by nicotine, whereas the total cellular amylase content was significantly increased. Analysis of competitive ligand binding data on membranes from isolated acini showed that the Bmax and Kd values for CCK receptors were not significantly changed by nicotine, p > 0.05. These data indicate that a postreceptor mechanism is involved in the inhibition in stimulus-secretion coupling of enzyme secretion by nicotine. The increase in total cellular amylase content and decreased enzyme secretion by nicotine may be implicated in the induction of pancreatic pathology.
We report a case of multiple liver metastasis from ileac carcinoid treated with continuous intraarterial infusion of somatostatin analog. A 65-year-old man who complained of chest pain was admitted to Yamaguchi University Hospital School of Medicine for further examination of cardiac angina. Liver tumors, which were detected during ECHO cardiogram examination, were diagnosed as metastasis from carcinoid by percutaneous transhepatic liver biopsy. Primary tumor was found at the ileum by colonofiberscopy. We performed ileo-cecal resection and catheterization from the gastroduodenal artery for intraarterial chemotherapy under laparotomy. After the operation, the patient was treated with continuous intraarterial infusion of somatostatin analog (100 micrograms/day, 5 days/week for 16 weeks). The tumor in segment 6 (S6) disappeared, but the tumor in S2 enlarged after the therapy. Hepatic angiography confirming the drug distribution demonstrated the occlusion of the left hepatic artery. This drug was thus distributed to the tumor in S6 but not in S2. These results suggest that somatostatin analog may have a direct anti-tumor effect. Furthermore, no side effect was observed. Thus, intraarterial infusion of somatostatin analog may be a useful therapy for liver metastasis from carcinoid.
A 75-year-old man with gastric cancer having multiple liver metastases was given intraarterial infusion therapy with sequential low-dose MTX (30 mg/body) and 5-FU (1,000 mg/body) for metastatic liver tumors one month after the primary gastric tumor was resected. This therapy was given once a week on admission and every two weeks while an outpatient. A total of 18 courses of this therapy produced marked regression and necrosis of liver metastases. The effect was thus rated as partial response. This patient survived 15 months after surgery. These results indicate that intraarterial infusion therapy with sequential low-dose MTX and 5-FU may be effective in multiple liver metastasis from gastric cancer.
M Nishikawa, Akira Tangoku, Y Hamanaka, T Suzuki and P L. Rayford : Gastric pH monitoring after pylorus preserving pancreaticoduodenectomy with Billroth I type of reconstruction., Journal of the American College of Surgeons, Vol.179, No.2, 129-134, 1994.
(要約)
A late complication of pancreaticoduodenectomy is anastomotic ulcer, and the complication is lessened when pancreaticoduodenectomy is accompanied by preservation of the pylorus. However, the results of some reports suggest that acid levels are not significantly different between patients who undergo pylorus preserving pancreaticoduodenectomy (PPPD) and those having standard pancreaticoduodenectomy. In this study, we measured gastric acidity in the same patients both before and after PPPD.
M Nishikawa, T Murakami, Akira Tangoku, H Hayashi, J Adachi and T Suzuki : Functioning of the intrathoracic stomach after esophagectomy., Archives of Surgery, Vol.129, No.8, 837-841, 1994.
(要約)
To investigate acid secretion and motility of the intrathoracic stomach with truncal vagotomy after esophagectomy.
Akira Tangoku, R Doi, P Chowdhury, G T. Blevins, J N. Pasley and P L. Rayford : Exogenous administration of estradiol and cholecystokinin alters exocrine pancreatic function in rats., The International Journal of Pancreatology, Vol.13, No.2, 81-86, 1993.
(要約)
This study was conducted in rats to investigate the influence of exogenously administered estradiol (ESD) and/or cholecystokinin (CCK) on components and secretions of the pancreatic acini. Intact male rats were treated for 14 d with exogenous administration of ESD, CCK, or ESD+CCK. After 14 d CCK treatment induced significant increases in DNA and RNA contents, and DNA/RNA ratio in the pancreas, indicating hyperplasia and hypertrophy of the pancreas, however, ESD treatment did not have these effects. Both ESD treatment and CCK treatment induced significant increases in amylase and trypsinogen contents in pancreatic acini and each decreased secretion from acini in response to CCK. Combined treatment with ESD plus CCK augmented these effects on enzyme contents and secretion. The results indicate that exogenous administration of CCK has trophic effects on the exocrine pancreas, increasing effects on enzyme contents and inhibitory effects on amylase secretion. In contrast, exogenous administration of ESD had no trophic effects on pancreas, but had increasing effects on enzyme contents and inhibitory effects on amylase secretion. The results suggest that the effects of exogenous ESD and CCK on pancreas are not similar to each other, but both ESD and CCK may be involved in regulating pancreatic exocrine functions.
Akira Tangoku, R Doi, P Chowdhury, G T. Blevins, J N. Pasley, L W. Chang and P L. Rayford : Humoral factors that induce alterations of the pancreas in rats with obstructive jaundice., Pancreas, Vol.8, No.1, 103-108, 1993.
(要約)
This study was conducted to investigate the role of humoral factors in pancreatic alterations induced by obstructive jaundice (OJ) in rats. OJ in male Sprague-Dawley rats induced significant increases in pancreatic weight, DNA content, and RNA content of acinar cells. These changes were accompanied by enlargement of eosinophilic granules and compressed nuclei. Protein, amylase, and trypsinogen contents of pancreas were also increased in OJ rats. In addition, plasma levels of bilirubin, cholecystokinin (CCK), and estradiol increased in OJ rats and were correlated positively with each other and with pancreatic weights. Administration of a specific CCK receptor, L-364,718, to OJ rats partly attenuated the changes of the pancreas, indicating that CCK is involved in these changes. These findings suggest that estradiol may be involved in regulating the pancreatic changes induced by OJ in rats.
Y Sato, H Tominaga, Akira Tangoku, Y Hamanaka, Y Yamashita and T Suzuki : Alpha-fetoprotein-producing cancer of the ampulla of Vater., Hepato-Gastroenterology, Vol.39, No.6, 566-569, 1992.
(要約)
A case of cancer of the ampulla of Vater producing alpha-fetoprotein is reported and the literature is reviewed. As far as we know, the literature contains no reports of such a case. The preoperative serum alpha-fetoprotein was remarkably high (7,480 ng/ml), but it fell to normal values (under 5.0 ng/ml) after pancreatoduodenectomy, by means of which the lesion could be radically resected. In this case, the immunohistochemical findings at optical and electron microscopy clearly indicated the production of alpha-fetoprotein by the cancer cells of the ampulla of Vater.
(キーワード)
Adenocarcinoma / Aged / Ampulla of Vater / Common Bile Duct Neoplasms / Humans / Male / Pancreaticoduodenectomy / alpha-Fetoproteins
(文献検索サイトへのリンク)
● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 1282896
Akira Tangoku, P Chowdhury, Y S. Huang, R Doi, G T. Blevins, C Eyiuche, D W. McKay and P L. Rayford : Exocrine pancreatic function in obstructive jaundice rats: studies with isolated dispersed pancreatic acini., The Journal of Surgical Research, Vol.53, No.4, 378-383, 1992.
(要約)
This study was conducted to investigate pancreatic exocrine function and pancreatic growth in rats with obstructive jaundice (OJ). OJ was produced in adult male Sprague-Dawley rats by bile duct ligation; control rats underwent laparotomy only. Induction of OJ was associated with significant hyperplasia and hypertrophy of the pancreas in rats as shown by increased DNA and RNA contents of pancreatic tissue. Factors associated with pancreatic growth in OJ rats were further examined in isolated dispersed pancreatic acini from OJ rats and the data were compared with those for control rats. Studies with isolated dispersed acini from OJ rats showed that pancreatic growth was accompanied by significant increases in total cellular amylase content; however, amylase release (percentage of initial) in response to cholecystokinin octapeptide was significantly decreased in OJ rats compared to control rats. Total amylase output in response to 100 pM cholecystokinin (CCK) was higher in the OJ group when compared to the control group (8.6 U/mg protein versus 6.4 U/mg protein), as calculated from the total amylase content and percentage of amylase released. Receptor binding data showed that the capacity of CCK receptors in OJ rats was significantly lower when it was compared with control. In addition, plasma levels of CCK were significantly elevated in OJ rats when compared to controls. These results suggest that obstructive jaundice induces pancreatic growth that is associated with alteration of exocrine pancreatic function. Abnormally high levels of stored amylase in pancreatic acini may be implicated in the development of pancreatitis as often seen in obstructive jaundice patients.
G T. Blevins, R Doi, Akira Tangoku, P Chowdhury, D McKay and P L. Rayford : Simultaneous measurement of cholecystokinin-stimulated amylase release and cholecystokinin receptor binding in rat pancreatic acini., The Journal of Laboratory and Clinical Medicine, Vol.119, No.5, 566-573, 1992.
(要約)
In the past, isolated-dispersed pancreatic acini have been used to examine either cholecystokinin-stimulated amylase release or pancreatic acinar cholecystokinin receptors. We have developed and validated a method for simultaneous measurement of synthetic cholecystokinin octapeptide-stimulated (CCK8-stimulated) pancreatic amylase release and cholecystokinin receptors. After an 18-hour fast, rats were killed and their pancreatic acini isolated. Three-milliliter aliquots of acinar suspension were incubated for 60 minutes in N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid-Ringer buffer containing graded doses of CCK8 and a constant amount (7 pmol/L) of iodine 125-labeled CCK8 (by the Bolton-Hunter method) ([125I]BH-CCK8). A 1 ml sample was removed from each flask for determination of amylase release, and the remaining 2 ml were used to determine cholecystokinin receptor capacities and affinities. The median effective dose for amylase release was 16 pmol/L, and release was maximal at 100 pmol/L CCK8 plus 7 pmol/L [125I]BH-CCK8, a dose that released 28% +/- 3% of total cellular amylase content. High affinity (equilibrium dissociation constant of high-affinity receptors = 58 +/- 8 pmol/L, receptor density of high-affinity receptors = 4 +/- 1 fmol/mg protein) and low affinity (equilibrium dissociation constant of low-affinity receptors = 7 +/- 2 nmol/L, receptor density of low-affinity receptors = 313 +/- 108 fmol/mg protein) cholecystokinin receptors were measured. The results demonstrate that CCK8-stimulated amylase release and cholecystokinin receptor binding in pancreatic acini can be measured concurrently and that the parameters of amylase release and cholecystokinin receptor binding are strikingly similar to those previously observed.(ABSTRACT TRUNCATED AT 250 WORDS)
R Doi, Akira Tangoku, K Inoue, P Chowdhury and P L. Rayford : Effects of FK506 on exocrine pancreas in rats., Pancreas, Vol.7, No.2, 197-204, 1992.
(要約)
The efficacy of FK506 on exocrine pancreas was studied in rats. Male Sprague-Dawley rats (230-250 g) received an i.m. daily injection of FK506 (0.1, 0.5, or 5.0 mg/kg), cyclosporine (CS; 25 mg/kg), or saline for 2 weeks. Isolated dispersed pancreatic acini were prepared from rats, and enzyme content of the cells and secretory response to cholecystokinin (CCK) were determined. Amylase and trypsin contents were increased in a dose-related manner by FK506 (p less than 0.01) and by CS at 25 mg/kg (p less than 0.01). The release of amylase in response to CCK was reduced by FK506 in a dose-related manner (p less than 0.01) and by CS at 25 mg/kg (p less than 0.01). Histologic examination showed that treatment of rats with FK506 at 0.1 mg/kg did not affect morphology of the acinar cells. FK506 at 0.5 mg/kg induced a minimal number of small vacuoles in cytoplasm of acinar cells and FK506 at 5.0 mg/kg, and CS at 25 mg/kg induced numerous cytoplasmic vacuoles and pyknotic nuclei. Increased enzyme storage and suppressed responsiveness of amylase release may have an association with the histologic changes. Therefore, the results of this study suggest that FK506, even when used in a low dose, may have adverse effects on the exocrine pancreas. Understanding of the mechanism of action of FK506 on pancreas will provide essential basic information that will allow transplant practitioners to more fully explore the benefits of this drug.
(キーワード)
Amylases / Animals / Male / Organ Size / Pancreas / Rats / Rats, Inbred Strains / Tacrolimus
(文献検索サイトへのリンク)
● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 1372739
Akira Tangoku, R Doi, P Chowdhury, J N. Pasley, D W. McKay and P L. Rayford : Use of a specific cholecystokinin receptor antagonist (L-364,718) to determine the role of cholecystokinin on feeding and body weight in rats with obstructive jaundice., Journal of the Association for Academic Minority Physicians, Vol.3, No.2, 38-40, 1992.
(要約)
We conducted a study to examine the role of cholecystokinin in feeding behavior and weight change in rats with obstructive jaundice. Daily food and water intake, body weight, and short-term food intake were determined in two groups of rats with surgically induced obstructive jaundice and in control rats. One group of rats with obstructive jaundice was given L-364,718, a selective cholecystokinin receptor antagonist. Plasma bilirubin and cholecystokinin levels were measured in each rat before and 7 days after surgery. Daily food intake and body weight were decreased in obstructive jaundice rats compared with control rats during the first week after surgery (P less than .05); however, obstructive jaundice rats treated with L-364,718 had increased food intake and body weight (P less than .05). Short-term food intake measured for 30 minutes and 120 minutes in food-deprived obstructive jaundice rats was decreased when compared with control rats (P less than .05), but the obstructive jaundice rats given L-364,718 had increased short-term food intake (P less than .05). Water intake was similar between the two groups of rats. Plasma levels of cholecystokinin and bilirubin were increased in obstructive jaundice rats with and without L-364,718 treatment (P less than .05). The results support the concept that endogenously elevated levels of plasma cholecystokinin play an important role in decreased food intake and subsequent loss of body weight in rats with obstructive jaundice.
R Doi, Akira Tangoku, K Inoue, P Chowdhury and P L. Rayford : Mechanisms by which FK 506 affects exocrine pancreas in rats., Transplantation Proceedings, Vol.23, No.6, 3161-3163, 1991.
(キーワード)
Amylases / 分散分析 (analysis of variance) / Animals / Dose-Response Relationship, Drug / Kinetics / Male / Pancreas / Rats / Rats, Inbred Strains / Reference Values / Tacrolimus
(文献検索サイトへのリンク)
● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 1721392
Akira Tangoku, M Nishikawa, A Adachi and T Suzuki : Plasma gastrin and cholecystokinin response after pylorus-preserving pancreatoduodenectomy with Billroth-I type of reconstruction., Annals of Surgery, Vol.214, No.1, 56-60, 1991.
(要約)
Plasma gastrin and cholecystokinin (CCK) responses were measured after a pancreatoduodenectomy (PD) using the Billroth-I type reconstruction combined with distal partial gastrectomy (standard PD) and combined with preservation of the pylorus and the duodenal bulb (PPPD). Six unoperated patients, 4 men and 2 women, were studied as control subjects. Basal plasma levels of gastrin were significantly higher in controls than in patients who had a standard PD (p less than 0.05) and gastrin responses to a meal were also blunted in these patients. In contrast basal and postprandial levels of gastrin after PPPD were significantly higher than these found in patients with standard PD (p less than 0.05). Postprandial gastrin response after PPPD were similar in pattern to these found in controls. Integrated gastrin release after PPPD was less than that of the control but was significantly greater than that in patients with standard PD. Basal plasma levels of CCK in the patients after the standard PD were significantly lower than in controls and significantly higher postprandial levels of CCK were found after PPPD compared to standard PD (p less than 0.05). However integrated CCK from 0 to 120 minutes were not significantly different between PPPD and standard PD groups. Based on these observations concerning hormonal release of gastrin and CCK, preservation of the stomach and the duodenal bulb appears to be a more physiologic reconstructive procedure than the standard PD. In addition the operation probably has more beneficial effect on the injured pancreas in time.
G T. Blevins, H S. Huang, Akira Tangoku, D W. Mckay and P L. Rayford : Estrogens influence cholecystokinin stimulated pancreatic amylase release and acinar cell membrane cholecystokinin receptors in rat., Life Sciences, Vol.48, No.16, 1565-1574, 1991.
(要約)
This study examines the influence of ovariectomy and administration of a pharmacologic dose of estradiol on amylase release from isolated-dispersed rat pancreatic acini and cholecystokinin receptors on rat acinar cell membranes. Rats were sham ovariectomized (intact) or ovariectomized (Ovx) and 21 day timed release pellets containing either estradiol (2.5 mg) or vehicle, were implanted subcutaneously. Eighteen days later, pancreatic acini were isolated from rats by collagenase digestion and differential centrifugation. Total cellular amylase, basal and cholecystokinin octapeptide (CCK8) stimulated amylase release and CCK membrane receptors were measured. Acini isolated from estradiol treated Ovx rats had significantly greater total cellular amylase, compared to acini isolated from either intact or Ovx rats. The amplitude of both total stimulated amylase release and percent total stimulated amylase release were significantly greater for acini isolated from vehicle treated Ovx rats, than acini isolated from either intact or estradiol treated Ovx rats. The magnitude of percent total amylase release of acini isolated from estradiol treated Ovx rats was significantly lower than that of acini isolated from intact rats. Cholecystokinin receptor concentration was significantly greater on membranes prepared from vehicle treated Ovx rats, compared to membranes prepared from either intact or estradiol treated Ovx rats. These data indicate that ovariectomy is associated with increased responsiveness of pancreatic acini to CCK stimulation, while chronic estradiol treatment of ovariectomized rats is associated with increased total cellular amylase and decreased acinar cell responsiveness to CCK8. Estrogen mediated alterations in acinar cell amylase content and amylase release may play a role in estrogen related pancreatitis.
Experimental achalasia dogs produced with Deloyer's method showed higher resting pressure at the gastroesophageal junction and the increase in LES pressure in response to tetragastrin and cholecystokinin. Dose-response curve of the LES to each dose of tetragastrin in achalasia dog shifted to the left. Resting LES pressure in 11 patients with achalasia was 42.73 +/- 23.31 cm H2O. It increased significantly after intramuscular injection of 5 micrograms/kg of tetragastrin and fluoroscopic observation showed the tonic contraction of the lower esophagus and cardia. After the performance of Jekler-Lhotka operation, LES pressure decreased to lower values sufficient to prevent the gastroesophageal reflux. Comparing 5 kinds of hiatal herniorrhaphies in dogs, LES pressure increased postoperatively in the following order: Nissen, Belsey Mark IV, Stensrud, Hill and Harrington methods. Responses to tetragastrin increased after Nissen and Belsey Mark IV methods. In 12 out of 21 clinical cases of sliding esophageal hiatal hernia who had undergone Nissen-Rossetti method adding fundopexy and posterior gastropexy, preoperative esophageal manometry showed HPZ of 24.98 +/- 8.87 cm H2O in peak value and 5.1 +/- 3.46 cm in length. Seven cases showed the biphasic pattern and 5 cases showed the negative response to tetragastrin. Postoperative manometry showed HPZ of 31.42 +/- 18.46 cm H2O in peak value and 4.5 +/- 1.73 cm in length. One case showed the biphasic pattern and 3 cases showed the negative response to tetragastrin.
A 66-year-old man underwent a curative operation for cecal cancer on the 30th of November, 1998. Since his CEA level rose in January 2001, computed tomography (CT) revealed a tumor in the abdomen. He underwent a resection of this tumor and disseminated tumors that were diagnosed during the operation. He received systemic chemotherapy (5'-DFUR 600 mg 3x everyday, CPT-11 80 mg/body div every 2 weeks), but the CEA level rose again in August 2003. He was diagnosed with spleen metastasis and underwent splenectomy. The tumor disseminated in the left diaphragm was also resected. After that, he received systemic chemotherapy (5-FU 500 mg/body/week div, levofolinate calcium 250 mg/body/week i.v.) as an outpatient. Peritoneal carcinomatosis from colorectal cancer with distant metastasis, in general, has no indication for an operation. However, if dissemination is located after a sufficient observation period, its resection may be recommended.
K. Muguruma, Kazuya Kondo, R. Kishibuchi, Mitsuhiro Tsuboi, S. Soejima, B. Tegshee, Koichiro Kajiura, Yukikiyo Kawakami, Naoya Kawakita, Mitsuteru Yoshida, Hiromitsu Takizawa and Akira Tangoku : DNA Methylation of MT1A and NPTX2 Genes Predict Malignant Behavior of Thymic Epithelial Tumors, The IASLC 20th World Conference on Lung Cancer, Sep. 2019.
2.
S. Soejima, Kazuya Kondo, Mitsuhiro Tsuboi, R. Kishibuchi, K. Muguruma, B. Tegshee, Koichiro Kajiura, Yukikiyo Kawakami, Naoya Kawakita, Mitsuteru Yoshida, Hiromitsu Takizawa, Akira Tangoku and N. Wusiman : GAD1 Expression and Its Methylation Become Indicators of Malignant Behavior in Thymic Epithelial Tumor, The IASLC 20th World Conference on Lung Cancer, Sep. 2019.
3.
Hiromitsu Takizawa, Toru Sawada, Mika Takashima, Daisuke Matsumoto, Naoya Kawakita, Mitsuhiro Tsuboi, Hiroaki Toba, Mitsuteru Yoshida, Yukikiyo Kawakami, Kazuya Kondo and Akira Tangoku : Autofluorescence Mode of Thoracoscope Improves Visceral Pleural Invasion Diagnosis in Non-Small Cell Lung Cancer, 19th World Conference on Lung Cancer, Sep. 2018.
4.
Naoya Kawakita, Hiromitsu Takizawa, Ali Eman, Mika Takashima, Daisuke Matsumoto, Toru Sawada, Mitsuhiro Tsuboi, Hiroaki Toba, Mitsuteru Yoshida, Yukikiyo Kawakami, Kazuya Kondo and Akira Tangoku : Cone-Beam CT Confirms the Status of Transbronchial Biopsy Under Virtual Bronchoscopic Navigation for Peripheral Lung Lesions, 19th World Conference on Lung Cancer, Sep. 2018.
5.
Hiromitsu Takizawa, Mika Takashima, Daisuke Matsumoto, Naoya Kawakita, Toru Sawada, Mitsuhiro Tsuboi, Hiroaki Toba, Mitsuteru Yoshida, Yukikiyo Kawakami, Kazuya Kondo and Akira Tangoku : CT and PET/CT Parameters of Lepidic Predominant Pattern Lung Adenocarcinoma and Invasiveness on Pathology, 19th World Conference on Lung Cancer, Sep. 2018.
6.
Kazuya Kondo, Soejima Shiho, wusiman nuliamina, Kishibuchi Reina, Mitsuhiro Tsuboi, Koichiro Kajiura, Yukikiyo Kawakami, Naoya Kawakita, Toru Sawada, Hiroaki Toba, Mitsuteru Yoshida, Hiromitsu Takizawa and Akira Tangoku : The expression of DNA methylation of GAD1 gene is an indicator of malignant behavior in thymic epithelial tumor, 19th World Conference on Lung Cancer, Sep. 2018.
7.
Seiya Inoue, Masakazu Goto, Takeshi Nishino, Takahiro Yoshida and Akira Tangoku : Oral PresentationTreatment Strategy of Esophageal Cancer from the Expression of HER2 and EGFR, International Society for Diseases of the Esophagus, Sep. 2018.
8.
Takeshi Nishino, Hiroaki Toba, Takahiro Yoshida, Seiya Inoue, Masakazu Goto and Akira Tangoku : Oral PresentationDiagnostic Utility of Endobronchial Ultrasonography for the Tracheobronchial Invasion of Esophageal Cancer, International Society for Diseases of the Esophagus, Sep. 2018.
9.
Akira Tangoku, Takeshi Nishino, Seiya Inoue, Masakazu Goto and Takahiro Yoshida : The Effects of the Herbal Medicine Daikenchuto(Tj-100) after Esophageal Cancer Resection, Open-Label, Randomized Controlled Trial, Esophagus, Vol.15, No.2, 75-82, Sep. 2018.
(要約)
Daikenchuto (TJ-100), a traditional Japanese herbal medicine, is widely used in Japan. Its effects on gastrointestinal motility and microcirculation and its anti-inflammatory effect are known. The purpose of this prospective randomized controlled trial was to investigate the effect of TJ-100 after esophagectomy in esophageal cancer patients. Forty patients for whom subtotal esophageal resection for esophageal cancer was planned at our institute from March 2011 to August 2013 were enrolled and divided into two groups at the point of determination of the operation schedule after informed consent was obtained: a TJ-100 (15 g/day)-treated group (n = 20) and a control group (n = 20). The primary efficacy end-points were maintenance of the nutrition condition and the recovery of gastrointestinal function. The secondary efficacy end-points were the serum C-reactive protein (CRP) level and adrenomedullin level during the postoperative course, the incidence of postoperative complications, and the length of hospital stay after surgery. We examined 39 patients because one patient in the TJ-100 group was judged as having unresectable cancer after surgery. The mean age of the TJ-100 group patients was significantly older than that of the control group patients.The rate of body weight decrease at postoperative day 21 was significantly suppressed in the TJ-100 group (3.6% vs. the control group: 7.0%, p = 0.014), but the serum albumin level was not significantly different between the groups. The recovery of gastrointestinal function regarding flatus, defecation, and oral intake showed no significant between-group differences, but postoperative bowel symptoms tended to be rare in the TJ-100 group. There was no significant between-group difference in the length of hospital stay after surgery. The serum CRP level at postoperative day 3 was 4.9 mg/dl in the TJ-100 group and 6.9 mg/dl in the control group, showing a tendency of a suppressed serum CRP level in the TJ-100 group (p = 0.126). The rate of increase in adrenomedullin tended to be high postoperatively, but there was no significant difference between the two groups. TJ-100 treatment after esophageal cancer resection has the effects of prompting the recovery of gastrointestinal motility and minimizing body weight loss, and it might suppress the excess inflammatory reaction related to surgery.
(キーワード)
Adrenomedullin / Aged / C-Reactive Protein / Defecation / Eating / Esophageal Neoplasms / Esophagectomy / Female / Gastrointestinal Tract / Humans / Length of Stay / Male / Middle Aged / Nutritional Status / Phytotherapy / Plant Extracts / Postoperative Complications / Prospective Studies / Recovery of Function / Serum Albumin / Weight Loss
Satomi Moriyama, Daisuke Hinode, Masami Yoshioka, Yuka Sogawa, Takeshi Nishino, Akira Tangoku and Daniel Grenier : Impact of the use of Kampo medicine in patients with esophageal cancer during chemotherapy: a clinical trial, 65th Annual Meeting of the Japanese Association for Dental Research, Showa University, Tokyo, Japan, Nov. 2017.
11.
Hiroki Nishiwaki, Takuya Ishimoto, Masatake Akutagawa, Takahiro Emoto, Emiko Yasuno, Akira Tangoku, Shinsuke Konaka and Yohsuke Kinouchi : Development of bioelectrical impedance measurement device for discrimination of the mammary tumor using switching circuit, Abstracts book of the 16th International Conference on Biomedical Engineering, 124, Singapore, Dec. 2016.
12.
澤田 徹, Kazuya Kondo, Mitsuhiro Tsuboi, Naoya Kawakita, Koichiro Kajiura, Hiroaki Toba, Yukikiyo Kawakami, Mitsuteru Yoshida, Hiromitsu Takizawa and Akira Tangoku : FDG-PET/CT Might Be a Predictor for Residual Disease in Advanced NSCLC after Chemoradiotherapy, 17th World Conference on Lung Cancer, Dec. 2016.
13.
Naoya Kawakita, Hiroaki Toba, 澤田 徹, Mitsuhiro Tsuboi, Koichiro Kajiura, Yukikiyo Kawakami, Mitsuteru Yoshida, Hiromitsu Takizawa, Kazuya Kondo and Akira Tangoku : Stratification of pStage I Lung Adenocarcinoma by the Scoring System Based on Prognostic Factors, 17th World Conference on Lung Cancer, Dec. 2016.
14.
Mitsuhiro Tsuboi, Kazuya Kondo, Koichiro Kajiura, Hiromitsu Takizawa, 澤田 徹, Naoya Kawakita, Hiroaki Toba, Yukikiyo Kawakami, Mitsuteru Yoshida and Akira Tangoku : Promoter Hypermethylation of DNA Mismatch Repair Gene hMLH1 of Lung Cancer in Chromate-Exposed Workers, 17th World Conference on Lung Cancer, Dec. 2016.
15.
Koichiro Kajiura, Kazuya Kondo, 澤田 徹, Naoya Kawakita, Mitsuhiro Tsuboi, Hiromitsu Takizawa and Akira Tangoku : The Relationship of CDH3 Expression and DNA Methylation in Thymic Epitherial Tumors, 17th World Conference on Lung Cancer, Dec. 2016.
16.
Seiya Inoue, Takeshi Nishino, Takahiro Yoshida and Akira Tangoku : Safety strategy for reconstruction with the jejunum-conduit for metachronous and synchronous gastrectomized patients with esophageal cancer, International Society for Diseases of the Esophagus, Sep. 2016.
17.
Takahiro Yoshida, Takeshi Nishino, Seiya Inoue, 松本 大資, 髙杉 遥, 森本 雅美, Kazumasa Okumura, Hirokazu Takechi and Akira Tangoku : Implications for improvement of gastro-esophageal reflux disease after esophagectomy, International Society for Diseases of the Esophagus, Sep. 2016.
18.
Akira Tangoku, Takahiro Yoshida and Seiya Inoue : Efficacy of prophylactic landiolol for atrial fibrillation in transthoracic esophagectomy, International Society for Diseases of the Esophagus, Sep. 2016.
19.
Akira Tangoku : N-1 study with S-1+low dose Docetaxel for advanced breast cancer patients, Official 10th European Breast Cancer Conference (EBCC-10), Mar. 2016.
20.
Koichiro Kajiura, Kazuya Kondo, 松本 大資, 河北 直也, Mitsuhiro Tsuboi, Hiroaki Toba, Yukikiyo Kawakami, Hiromitsu Takizawa, Shoji Sakiyama and Akira Tangoku : DNA Methylation on Promotor Region of RASSF1 Gene in Thymic Neuroendocrine Tumor Is Higher than B3 Thymoma and Thymic Squamous Cell Carcinoma, 16th World Conference on Lung Cancer, Sep. 2015.
21.
Mitsuhiro Tsuboi, Hiromitsu Takizawa, Daisuke Matsumoto, Naoya Kawakita, Koichiro Kajiura, Hiroaki Toba, Yukikiyo Kawakami, Shoji Sakiyama, Kazuya Kondo and Akira Tangoku : The Correlation between Visceral Pleural Invasion in T1a Non-Small Lung Cancer and Lymph Node Metastasis, 16th World Conference on Lung Cancer, Sep. 2015.
22.
Kazuya Kondo, Tomoko Kawanishi, Mariko Shiraishi, Chikako Takai, Yuki Morimoto, Tamaki Otani, Mitsuhiro Tsuboi, Koichiro Kajiura, Hiromitsu Takizawa, Gokei Kawakami, Hiroaki Toba, Shoji Sakiyama and Akira Tangoku : The MRE11/RAD50/NBS1 Complex Was Impaired in Lung Cancer from Chromate-Exposed Workers, 16th World Conference on Lung Cancer, Sep. 2015.
23.
Hiromitsu Takizawa, Kazuya Kondo, Mitsuhiro Tsuboi, Koichiro Kajiura, Tamaki Otani, Hiroaki Toba, Yukikiyo Kawakami, Shoji Sakiyama and Akira Tangoku : Mini OralComputed Tomography Lymphography by Transbronchial Injection of Iopamidol for Preoperative, 16th World Conference on Lung Cancer, Sep. 2015.
24.
Yukiko Tadokoro, 森本 雅美, Misako Nakagawa, Hirokazu Takechi and Akira Tangoku : Phase II study with S-1+low dose Docetaxel (N-1 study) for operable breast cancer patients, 14th St. Gallen International Breast Cancer Conference 2015 (BCC2015), Mar. 2015.
25.
Misako Nakagawa, Masami Morimoto, Hirokazu Takechi, Yukiko Tadokoro and Akira Tangoku : Preoperative diagnosis for metastasis of sentinel lymph node (SLN) using 3D CT lymphography (CTLG), 14th St. Gallen International Breast Cancer Conference 2015 (BCC2015), Vol.23, No.3, 519-524, St. Gallen, Mar. 2015.
Akira Tangoku : Estimation of sentinel lymph node metastasis with CT lymphography after primary chemotherapy, 14th St. Gallen International Breast Cancer Conference 2015 (BCC2015), Mar. 2015.
27.
Akira Tangoku, Takahiro Yoshida, Yoshihito Furukita, 西野 豪志, Hirokazu Takechi and 森下 敦司 : Timely Multimodality Therapy can realize long Survival for Advanced Espophageal Cancer Patients with Esophago-Broncheal Fistula, 14th World Congress of the International Society for Diseases of the Esophagus, Sep. 2014.
28.
Takeshi Nishino, Takahiro Yoshida, Yoshihito Furukita, Hirokazu Takechi, Yota Yamamoto, Yasuhiro Yuasa, Masakazu Goto, Takuya Minato, Seiya Inoue, Satoshi Fujiwara, Toru Sawada, Naoya Kawakita, Hiromichi Yamai, Jun-ichi Seike, Takanori Miyoshi and Akira Tangoku : Gender Differences in Clinicopathologic Features and Outcomes of Esophageal Cancer Patients, 14th World Congress of the International Society for Diseases of the Esophagus, Sep. 2014.
29.
Takahiro Yoshida, Yoshihito Furukita, Takeshi Nishino, Hirokazu Takechi, Yasuhiro Yuasa, Yota Yamamoto, Masakazu Goto, Takuya Minato, Seiya Inoue, Satoshi Fujiwara, Toru Sawada, Naoya Kawakita, Miyuki Kanematsu, Hiromichi Yamai, Junichi Seike, Takanori Miyoshi and Akira Tangoku : Sentinel Lymph Node Navigation Surgery Using Preoperative CT Lymphography for Esophago-gastric Junctional Carcinomas, 14th World Congress of the International Society for Diseases of the Esophagus, Sep. 2014.
30.
Yoshihito Furukita, Akira Tangoku, 藤原 聡史, 井上 聖也, 西野 豪志, Masakazu Goto, 湊 拓也, Yota Yamamoto, 湯浅 康弘, 山井 礼道, Hirokazu Takechi, Takahiro Yoshida and Jun-ichi Seike : New Minimal Invasive Strategy for Superficial Esophageal Cancer, 26th International Conference of the Society for Medical Innovation and Technology, Sep. 2014.
31.
Mitsuteru Yoshida, Shoji Sakiyama, 日野 弘之, 高嶋 美佳, Mitsuhiro Tsuboi, Koichiro Kajiura, Hiroaki Toba, Yasushi Nakagawa, Yukikiyo Kawakami, Hiromitsu Takizawa, Kazuya Kondo and Akira Tangoku : Anatomical Anomaly Cases Of General Thoracic Surgery, American Thoracic Society International Conference2014, San Diego, May 2014.
32.
Shoji Sakiyama, Mitsuteru Yoshida, Yukikiyo Kawakami, Koichiro Kenzaki, Mitsuhiro Tsuboi, Koichiro Kajiura, Yasushi Nakagawa, Hiromitsu Takizawa, Kazuya Kondo and Akira Tangoku : Glucocorticoid Administration Facilitates The Differentiation Of Rat Fetal Lung Fragments Into Adult Rat Lung Parenchyma, American Thoracic Society International Conference2014, San Diego, California, May 2014.
33.
Yasushi Nakagawa, Kazuya Kondo, Jun Nakajima, Meinoshin Okumura, Ichiro Yoshino, Yoshitaka Fujii, Hisao Asamura, Kazuo Yoshida, Hiroshi Date, Kanji Nagai, Kohei Yokoi, Shinichiro Miyoshi, Shoji Sakiyama and Akira Tangoku : Analysis of lymphatic metastases of thymic epithelial tumors on Japanese database, 15th World Conference on Lung Cancer, Oct. 2013.
34.
Koichiro Kajiura, Shoji Sakiyama, Hiromitsu Takizawa, Yasushi Nakagawa, Kazuya Kondo and Akira Tangoku : Prophylactic landiolol administration can prevent atrial fibrillation after lobectomy?, 15th World Conference on Lung Cancer, Oct. 2013.
35.
Hiromitsu Takizawa, Kazuya Kondo, Tamaki Otani, Ali M. Mohammed, Hideki Otsuka, Mitsuhiro Tsuboi, Koichiro Kajiura, Yasushi Nakagawa, Yukikiyo Kawakami, Mitsuteru Yoshida, Shoji Sakiyama and Akira Tangoku : Positron-emission tomography-computed tomography with the glucose analogue [18F] fluorodeoxyglucose in orthotopic implantation SCID mouse model of lung cancer, 15th World Conference on Lung Cancer, Oct. 2013.
36.
Mitsuhiro Tsuboi, Hiromitsu Takizawa, Kazuya Kondo, Hisashi Ishikura, Suguru Kimura, Koichiro Kajiura, Yasushi Nakagawa, Yukikiyo Kawakami, Mitsuteru Yoshida, Shoji Sakiyama and Akira Tangoku : A feasibility study of postoperative adjuvant chemotherapy with fluoropyrimidine S-1 in patients with stage II-IIIA non-small cell lung cance, 15th World Conference on Lung Cancer, Oct. 2013.
37.
Hiromitsu Takizawa, Kazuya Kondo, Hiroaki Toba, Koichiro Kajiura, Mayumi Ikeda, Takako Furukawa, Takeshi Nishino, Yasushi Nakagawa, Mitsuteru Yoshida, Yukikiyo Kawakami, Shoji Sakiyama and Akira Tangoku : PREOPERATIVE AND INTRAOPERATIVE IDENTIFICATION OF SENTINEL NODES IN PATIENTS, THE 21ST ANNUAL MEETING OF THE ASIAN SOCIETY FOR CARDIOVASCULAR AND THORACIC, Apr. 2013.
38.
Yoshie Imai, Misako Nakagawa, Chiemi Onishi, Keiko Mori, Takae Bando, Kazuya Kondo and Akira Tangoku : Symptoms and knowledge of lymphedema among postoperative breast cancer patients without lymphedema, Prague, Sep. 2012.
39.
Yota Yamamoto, Akira Tangoku, H. Yamai, T. Minato, Yoshihito Furukita, Hirokazu Takechi and Jun-ichi Seike : The human epidermal growth factor receptor(HER)family as the predictor of sensitivity to chemotherapy and, INTERNATIONAL SURGICAL WEEK/ISW2011, Aug. 2011.
40.
Y. Fujita, Kazuya Kondo, A.H.K. Ali, T. Namura, Y. Senba, Y. Oiwa, C. Takai, Hiromitsu Takizawa, Yasushi Nakagawa, Hiroaki Toba, Koichiro Kenzaki, Shoji Sakiyama and Akira Tangoku : Polymorphisms in x-ray repair cross-complementing group 1 (XRCC1) base excision repair gene and lung cancer risk in industrial workers with chromate exposure, 14TH WORLD CONFERENCE ON LUNG CANCER, Jul. 2011.
41.
A.H.K. Ali, Hiromitsu Takizawa, Kazuya Kondo, Yasushi Nakagawa, Hiroaki Toba, N. Khasag, Koichiro Kenzaki, Shoji Sakiyama and Akira Tangoku : Follow- up using fluorescence bronchoscopy for the patients with photodynamic therapy treated early lung cancer, 14TH WORLD CONFERENCE ON LUNG CANCER, Jul. 2011.
42.
M. Takashima, Hiromitsu Takizawa, K. Kajiura, K. Uyama, Hiroaki Toba, Yasushi Nakagawa, Yukikiyo Kawakami, Koichiro Kenzaki, Shoji Sakiyama, Kazuya Kondo and Akira Tangoku : Comparison of two different EGFR gene mutation tests for resected lung adenocarcinoma, 14TH WORLD CONFERENCE ON LUNG CANCER, Jul. 2011.
43.
K. Kajiura, Hiroaki Toba, Shoji Sakiyama, M. Takashima, K. Uyama, Yasushi Nakagawa, Hiromitsu Takizawa, Yukikiyo Kawakami, Koichiro Kenzaki, Kazuya Kondo and Akira Tangoku : Experience of TBLB using thin bronchoscopy with VBN, 14TH WORLD CONFERENCE ON LUNG CANCER, Jul. 2011.
44.
H. Matsuoka, Kazuya Kondo, Hiromitsu Takizawa, H. Fujino, K. Uyama, Hiroaki Toba, Koichiro Kenzaki, Shoji Sakiyama and Akira Tangoku : Comprehensive evaluation of the responded genes by the administration of anti-tumor drug, S-1 using low, 14TH WORLD CONFERENCE ON LUNG CANCER, Jul. 2011.
45.
Hiromitsu Takizawa, Kazuya Kondo, Hiroaki Toba, K. Kajiura, M. Takashima, K. Uyama, Yasushi Nakagawa, Yukikiyo Kawakami, Koichiro Kenzaki, Shoji Sakiyama and Akira Tangoku : Computed tomography lymphography by transbronchial injection of a water-soluble extracellular CT, 14TH WORLD CONFERENCE ON LUNG CANCER, Jul. 2011.
46.
Akira Tangoku : New strategy for treatment of esophageal cancer, VIETNAM-JAPAN JOINT WORKSHOP ON CANCER TREATMENT, Dec. 2010.
47.
Junko Honda, Taeko Nagao, Misako Nakagawa, Takahashi Masako, Akira Tangoku, Zembutsu Hitoshi, Nakamura Yusuke and Sasa Mitsunori : SERUM ESTRADIOL SHOULD BE MONITORED NOT ONLY DURING THE PERI-MENOPAUSAL, The Sixth International Symposium on Hormonal Oncogenesis, Sep. 2010.
48.
中川 美砂子, Morimoto Masami, Ikeda Mayumi, Misaki Mariko, 坂東 良美, Sasa Mitsunori, 丹黒 章 : PROGNOSTIC BIOMARKERS IN TRIPLE NEGATIVE BREAST CANCER, The Sixth International Symposium on Hormonal Oncogenesis, 2010年9月.
49.
Jun-ichi Seike, Yoshihito Furukita, Yota Yamamoto, Hirokazu Takechi, Takahiro Yoshida and Akira Tangoku : Mediastinoscope-assisted transhiatal esophagectomy, 12th World Congress of the ISDE, Sep. 2010.
50.
Yota Yamamoto, H. Yamai, Yoshihito Furukita, Hirokazu Takechi, Takahiro Yoshida, Jun-ichi Seike and Akira Tangoku : The human epidermal growth factor receptor(HER) family are the predictor of sensitivity to chemotherapy, 12th World Congress of the ISDE, Sep. 2010.
51.
Yoshihito Furukita, Yota Yamamoto, M. Kanematsu, M. Morimoto, S. Inoue, S. Fujiwara, Hirokazu Takechi, Jun-ichi Seike and Akira Tangoku : Evaluation of first-line chemotherapy with docetaxel/CDDP/5-FU for advanced esophageal cancer, 12th World Congress of the ISDE, Sep. 2010.
52.
Akira Tangoku, Jun-ichi Seike, Hirokazu Takechi, Yota Yamamoto, Yoshihito Furukita, S. Inoue, S. Fujiwara, M. Morimoto, M. Kanematsu and M. Takashima : A new minimal invasive strategy for superficial esophageal cancer: sentinel lymph node, 12th World Congress of the ISDE, Sep. 2010.
53.
Khalil Hamed Abdellah, Hiromitsu Takizawa, Kazuya Kondo, Matsuoka Hisashi, Hiroaki Toba, Yasushi Nakagawa, Koichiro Kenzaki, Shoji Sakiyama, Kakiuchi Soji, Saburo Sone and Akira Tangoku : In vitro and in vivo photodynamic diagnosis using 5-aminolevulinic acid in malignant mesothelioma, The 10th International Conference of the International Mesothelioma Interest Group, Aug. 2010.
54.
Misako Nakagawa, Morimoto Masami, Taeko Nagao, Yasushi Nakagawa and Akira Tangoku : Preoperative diagnosis of sentinel lymph node(SLN) metastasis using 3D CT lymphography(CTLG), American Society of Clinical Oncology 46th Annual Meeting, Jun. 2010.
55.
Aki Takahashi, Takahiro Yoshida, Takae Bando, Yoshie Imai, Takeshi Nishino, Seiya Inoue, Akira Tangoku and Kazuya Kondo : Quality of Life and Psycholugical Status ofPatients with Esophageal Cancer Who Underwent Minimal Invasive Surgery, 2nd Technological Competrncy as Caring inthe Health Sciences 2018, 111, Aug. 2008.
56.
Emiko Yasuno, Xueli Zhao, Yohsuke Kinouchi, Tadaoki Morimoto, Akira Tangoku, Okazaki Kenji, Ikeda Yuichi, Sato Yasuhiro and Ichida Teruhiro : A fundamental study on theory of space distribution estimation for EIT, Proceedings of the International Symposium on Biological and Physiological Engineering /The 22nd SICE Symposium on Biological and Physiological Engineering, 353-354, Harbin, Jan. 2008.
(キーワード)
bio-impedance / tissue equivalent circuit model / Gauss-Newton metohd
57.
Teruhiro Ichida, Yuichi Ikeda, Emiko Yasuno, Kenji Okazaki, Yasuhiro Sato, Akira Tangoku, Yohsuke Kinouchi and Tadaoki Morimoto : Improvement of bio-impedance measurement accuracy with guard electrodes approach, International journal of bioelectromagnetism, Vol.9, No.1, 126-127, Aizuwakamatsu, Oct. 2007.
58.
Ikeda Yuichi, Sato Yasuhiro, Yohsuke Kinouchi, Emiko Yasuno, Omine Yuken, Akira Tangoku and Tadaoki Morimoto : Nomivasive Estimation of Tissue Impedance Based on an Equivalent Circuit Model, Proceedings of the Intenational Conference on Biomedical and Pharmaceutical Engineering, 246-251, Singapore, Dec. 2006.
59.
Arisa Morimoto, Emiko Yasuno, Yohsuke Kinouchi, Y Omine, Akira Tangoku and Tadaoki Morimoto : Spatial Resolution in the Electrical Impedance Tomography for the Local Tissue, Proceedings of the 27th Annual Conference of the IEEE-EMBS, Vol.7, 6638-6641, Shanghai, Sep. 2005.
Takanori Miyoshi, Kazuya Kondo, Hiromitsu Takizawa, Kouichirou Kenzaki, Haruhiko Fujino, Shoji Sakiyama and Akira Tangoku : P-171 Fluoroscopy-assisted thoracoscopic resection of pulmonarynodules after computed tomography-guided bronchoscopic metallic coil marking using virtual bronchoscopy navigation, Lung Cancer, Vol.49, No.supplement2, s160, Feb. 2005.
61.
Akira Tangoku : Mediastinoscope Assisted trans-hiatal Esophagectomy (MATHE) for Esophageal Cancer, Audiovisual Symposium : Esophageal Cancer 2 IX th International Congress of Disease of the Esophagus, 26-29, Madrid,Spain, May 2004.
62.
Akira Tangoku : Wat's new in chemotherapy for palliation, Symposium Palliation of esophageal cancer IX th International Congress of Disease of the Esophagus, 26-29, Madrid,Spain, May 2004.