A case of matrix-producing carcinoma of the breast.

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 Case of Solitary Para-Aortic Lymph Node Metastasis of Hepatocellular Carcinoma Treated with Single Resection

肝細胞癌孤立性大動脈周囲リンパ節転移の1切除例

We report a case of the which was treated with TAE, RFA and surgery. In 2003, a 60-year-old man followed up for chronic hepatitis C and admitted for examination of intrahepatic lesions detected in urtrasonography was found in abdominal computed tomography (CT) to have two intrahepatic masses of about 4cm and 4.5cm and a solitary swollen 2.8cm lymph node to the right of the aorta. We diagnosed the intrahepatic lesions as hepatocellular carcinoma (HCC), but we could not diagnose the paraaortic lesion as a metastatic lymph node. We treated the hepatic lesion with TAE and RFA, and followed up the paraaortic mass, which became enlarged two months later. We resected the lymph node. The postoperative course was uneventful and the patient was discharged. Serum AFP decreased from a preoperative 2,685ng/ml to a postoperative 3ng/ml. Two years later, neither intrahepatic recurrence nor the presence of the metastatic lymph node was seen.

肝細胞癌の孤立性大動脈周囲リンパ節転移に対し,切除を行い良好な経過を得た症例を経験したので報告する.症例は60歳代の男性で,C型肝炎を経過観察中の2005年に腹部超音波検査で肝内腫瘤を指摘され当院紹介となった.CTで肝内に4cmと4.5cmの肝細胞癌を2個認め,大動脈周囲に2.8cmの孤立性腫瘤を認めた.大動脈周囲の孤立性腫瘤はリンパ節転移を疑ったが,鑑別診断に難渋したため,肝内病変の治療を先行し,経皮的局所療法を施行した.2か月の経過観察中に大動脈周囲の腫瘤は著明に増大傾向を示した.リンパ節転移としても孤立性であり,また,下大静脈と接することより,今後増大すれば予後因子と成りうると判断し,切除を行った.術後経過は良好で,術前2,685ng/mlと高値を示したAFPは3か月後には3ng/mlと著明に低下した.現在2年を経過するがAFPの上昇,再発は認めていない.肝細胞癌大動脈周囲孤立性リンパ節転移の報告はまれであり報告する.

The Japanese Journal of Gastroenterological Surgery


Complete response in a case of advanced esophageal cancer treated with docetaxel/5-FU/CDDPand S-1/docetaxel as neoadjuvant chemotherapy

Docetaxel/5‐FU/CDDP療法およびS‐1/Docetaxel療法による術前化学療法にて病理学的CRが得られた進行食道癌の1例

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.

Japanese Journal of Cancer and Chemotherapy


Approach by clamshell incision for bilateral pulmonary metastasis

手術の工夫 両側転移性肺腫瘍に対するclamshell incisionによるアプローチ

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.

The Japanese Journal of Thoracic Surgery


Thymidine phosphorylase and dihydropyrimidine dehydrogenase are predictive factors of therapeutic efficacy of capecitabine monotherapy for breast cancer-preliminary results.

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.

The Journal of Medical Investigation : JMI


Clinical experience with 16 cases of mediastinal lymphoma

縦隔悪性リンパ腫の臨床的検討

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.


Effect of mediastinal lymph nodes sampling in patients with clinical stage I non-small cell lung cancer

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.


Comparison of 3.0-and 1.5-tesla diffusion-weighted imaging in the visibility of breast cancer.

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.


Photodynamic therapy using a second generation photosensitizer, Talaporfin

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 elderly case of advanced cervical esophageal cancer successfully treated with UFT after chemoradiotherapy with docetaxel/5-FU/CDDP

Docetaxel/5‐FU/CDDP併用化学放射線療法後UFT単独外来投与が有効であった高齢者進行頸部食道癌の1例

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.

Japanese Journal of Cancer and Chemotherapy


Bilateral male breast cancer with male potential hypogonadism.

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.


Chromosomal aneusomy (chr 1, 11, 17) detected by fluorescence in situ hybridization may be a prognostic factor in breast cancer.

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.


Current status of sentinel lymph node navigation surgery in breast and gastrointestinal tract.

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.

The Journal of Medical Investigation : JMI


Two cases of bronchogenic cyst with severe adhesion to the trachea

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.

The Journal of Medical Investigation : JMI


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

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.


False-positive in fine-needle aspiration cytology of breast disease can be reduced with p63 immunostaining- A preliminary report

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.


A case of early relapsed multiple lung metastases after esophagectomy successfully treated with S-1/cisplatin therapy after docetaxel/5-fluorouracil/cisplatin therapy.

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.


The reduced expression and aberrant methylation of p16(INK4a) in chromate workers with lung cancer.

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.


Problems in histological grading of malignancy and its clinical significance in patients with operable breast cancer.

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.


Evaluation of safety and efficacy for bi-weekly Docetaxel and 5'-DFUR combination therapy in patients with advanced or recurrent breast cancer--Phase I study

進行・再発乳癌に対するBi‐weekly Docetaxelと5′‐DFURの併用化学療法における安全性と効果の検討—第I相試験—

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.

Japanese Journal of Cancer and Chemotherapy


Clinical analysis of operative and hospital deaths in primary lung cancer

胸部外科の指針 原発性肺癌における手術死亡および在院死亡

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.

The Japanese Journal of Thoracic Surgery


Lung regeneration: implantation of fetal rat lung fragments into adult rat lung parenchyma.

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.

Journal of Thoracic and Cardiovascular Surgery


Fluoroscopy-assisted thoracoscopic resection of pulmonary nodules after computed tomography--guided bronchoscopic metallic coil marking.

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.


CT lymphography-navigated sentinel lymph node biopsy in patients with superficial esophageal cancer.

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.


Lymphatic drainage from esophagogastric tract: feasibility of endoscopic CT lymphography for direct visualization of pathways.

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.


[Evaluation of host immunity and side effects in breast cancer patients treated with adjuvant chemotherapy (FEC therapy)]

乳癌術後補助化学療法(FEC療法)における免疫能および副作用の検討

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.


Photodynamic therapy for submucosal tumor of the central bronchus

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.

The Journal of Medical Investigation : JMI


甲状腺髄様癌術後肝転移に対し肝動脈化学塞栓療法が有効であった1例

甲状腺髄様癌術後肝転移に対し肝動脈化学塞栓療法が有効であった1例


Breast sentinel lymph node navigation with three-dimensional interstitial multidetector-row computed tomographic lymphography.

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.


Lower axillary dissection in breast cancer surgery may be candidate for cases with early breast cancer.

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.


Spatial resolution in the electrical impedance tomography for the local tissue.

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.

Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society


Risk factors for postoperative liver failure after hepatectomy for hepatocellular carcinoma.

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.


Molecular signature linked to acquired resistance to cisplatin in esophageal cancer cells.

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.


Mediastinoscope-assisted transhiatal esophagectomy for esophageal cancer


Molecular signature in three types of hepatocellular carcinoma with different viral origin by oligonucleotide microarray

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.


Sentinel lymph node biopsy using computed tomography-lymphography in patients with breast cancer

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.


Breast sentinel lymph node mapping at CT lymphography with iopamidol: preliminary experience

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.


Analysis of DNA copy number aberrations in hepatitis C virus-associated hepatocellular carcinomas by conventional CGH and array CGH

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.


Altered Levels of Cytochrome P450 Genes in Hepatitis B or C Virus-infected Liver Identified by Oligonucleotide Microarray


Gene expression profile linked to p53 status in hepatitis C virus-related hepatocellular carcinoma

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.


Identification of common or distinct genes related to antitumor activities of a medicinal herb and its major component by oligonucleotide microarray

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.


Prediction of nodal metastasis by comparative genomic hybridization in biopsy specimens from patients with superficial esophageal squamous cell carcinoma

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.


Detection of amplified oncogenes by genome DNA microarrays in human primary esophageal squamous cell carcinoma:comparison with conventional comparative genomic hybridization analysis

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.


Clinical evaluation of intrapleural or peritoneal administration of lentinan and OK-432 for malignant effusion

癌性胸腹水に対するLentinan+OK-432併用療法の臨床的検討

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.

Japanese Journal of Cancer and Chemotherapy


A case of Vp4 hepatocellular carcinoma treated with surgical resection and continuous intrahepatic artery infusion chemotherapy of low-dose cisplatin and 5-fluorouracil

Vp4肝細胞癌術後Low-Dose CDDP+5-FU肝動注療法が肝内再発に有効であった1例

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.


[Significance of intracellular cytokines levels in peripheral lymphocytes for evaluation of surgical stress after hepatectomy in patients with hepatocellular carcinoma].

肝癌切除の手術侵襲評価におけるCD4陽性リンパ球内サイトカイン測定の意義

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.


食道良性疾患の外科治療 6．食道憩室

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.


Differential gene expression in distinct virologic types of hepatocellular carcinoma: association with liver cirrhosis

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.


Oligonucleotide microarray for prediction of early intrahepatic recurrence of hepatocellular carcinoma after curative resection

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.


Visualization of Breast Lymphatic Pathways With an Indirect Computed Tomography Lymphography Using a Nonionic Monometric Contrast Medium Iopamidol: Preliminary Results

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.


Effects of moderate hypothermia on proinflammatory cytokine production in a rat model of caerulein-induced pancreatitis

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.


Telomerase Activity and Nm23-H2 Protein Expression in Hepatocellular Carcinoma

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.


[Hepatic arterial infusion of IL-2 and chemotherapy for unresectable liver metastasis from colorectal cancer].

当科における大腸癌肝転移に対するIL‐2，5‐FU，MMC併用肝動注療法の経験

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.

Japanese Journal of Cancer and Chemotherapy


[An autopsy case of sepsis following radiofrequency ablation (RFA) for metastatic liver carcinoma after bile duct reconstruction].

胆道再建術後転移性肝癌に対してラジオ波焼灼療法(RFA)施行後に敗血症を来した1剖検例

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.


Osteopontin expression in chronic pancreatitis.

Chronic pancreatitis (CP) is frequently associated with stone formation within the pancreatic duct system. The mechanism of pancreatic stone formation, however, is still unclear.


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.

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.


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.

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.


Anticachectic effects of the natural herb Coptidis rhizoma and berberine on mice bearing colon 26/clone 20 adenocarcinoma.

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.


Expression of estrogen receptor-alpha and -beta mRNAs in human gastric cancer.

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.


Gain of 5p15 detected by comparative genomic hybridization as an independent marker of poor prognosis in patients with esophageal squamous cell carcinoma.

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.


[Local therapy for stage IV advanced breast cancer with brain metastasis].

脳転移を伴うStage IV進行乳癌に対する局所療法

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.

Japanese Journal of Cancer and Chemotherapy


[Combined hepatocellular carcinoma and cholangiocellular carcinoma].

肝細胞癌と胆管細胞癌の混合型

Nihon Rinsho. Japanese Journal of Clinical Medicine


Failure to detect a huge Meckel's diverticulum with abundant ectopic gastric mucosa on gastric mucosal scintigraphy with Tc-99m pertechnetate.


Interleukin-6 production in lung tissue after transthoracic esophagectomy.

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.

Journal of the American College of Surgeons


Downregulation of intracellular nm23-H1 prevents cisplatin-induced DNA damage in oesophageal cancer cells: possible association with Na(+), K(+)-ATPase.

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.


Immunoregulatory effects of the antitumor polysaccharide lentinan on Th1/Th2 balance in patients with digestive cancers.

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.


[Significance of reduction surgery for giant hepatocellular carcinoma with diffuse lung metastases and multiple intrahepatic metastases].

び慢性肺転移および残肝多発転移を伴う巨大肝細胞癌症例に対する減量手術としての下大静脈合併拡大肝右葉切除術

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.


[Hepatocellular carcinoma with tumor thrombus in the portal and hepatic veins treated successfully with hepatectomy and chemotherapy--a case report].

門脈内(Vp2)および下大静脈内腫よう栓(Vv3)と肺転移を伴った肝細胞癌に対し外科切除と化学療法を施行した1例

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.


Detection of telomerase activity in peritoneal lavage fluid from patients with gastric cancer using immunomagnetic beads

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.


Anticachectic effects of Coptidis rhizoma, an anti-inflammatory herb, on esophageal cancer cells that produce interleukin 6.

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 achalasia of the esophagus].

食道アカラシアにおける治療最近の動向 6． 食道アカラシアに対するバルーン拡張術

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.


Lymph node metastases identified with mediastinoscopy in a patient with superficial carcinoma of the esophagus.

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.


Cytogenetic analysis of esophageal squamous cell carcinoma cell lines by comparative genomic hybridization: relationship of cytogenetic aberrations to in vitro cell growth.

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.


Gains of 8q23-qter and 20q and loss of 11q22-qter in esophageal squamous cell carcinoma associated with lymph node metastasis.

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.


Inhibitory effect of Coptidis Rhizoma and berberine on the proliferation of human esophageal cancer cell lines.

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.


Esophageal perforation and mediastinal abscess following placement of a covered self-expanding metallic stent and radiation therapy in a cancer patient.

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.


Laparoscopic resection of large leiomyomas of the gastric fundus.

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.


[Study of continuous arterial infusion chemotherapy with low-dose cisplatin and 5-fluorouracil for patients with hepatocellular carcinoma].

肝細胞癌に対するLow‐Dose CDDP+5‐FU肝動注療法の位置づけ

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.

Japanese Journal of Cancer and Chemotherapy


[A case of multiple liver metastases from breast cancer successfully treated with intra-arterial administration of docetaxel].

Docetaxel肝動注が奏効した乳癌肝転移の1例

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.


The nm23-H1 gene as a predictor of sensitivity to chemotherapeutic agents in oesophageal squamous cell carcinoma

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.


Wire-guided transoral esophagogastrostomy for carcinoma of the cervical esophagus.

Journal of the American College of Surgeons