Particulate hexavalent chromium exposure induces DNA double-strand breaks and inhibits homologous recombination repair in rat and human lung tissues

Lung cancer is an important human health concern because of its high mortality rate, with many cases caused by environmental chemicals other than tobacco. Particulate hexavalent chromium [Cr(VI)] is a well-established human lung carcinogen, but how Cr(VI) induces lung cancer is poorly understood. Chromosome instability, a hallmark of lung cancer, is considered a major driving factor in Cr(VI)-induced lung cancer. Our previous studies in cultured human lung cells showed that particulate Cr(VI) induces DNA double-strand breaks during the late S and G2 phases of the cell cycle, which are repaired by homologous recombination, one of the main repair pathways of DNA double-strand breaks. Our previous data showed that prolonged exposure to Cr(VI) inhibits homologous recombination repair by targeting RAD51, a key protein that mediates homologous recombination. Therefore, particulate Cr(VI)-induced DNA damage combined with failure of DNA repair can lead to chromosome instability. In this study we translated these results to rat lung tissue and lung tumor tissue from Cr(VI)-exposed workers. Wistar rats were exposed to zinc chromate in a saline solution or saline alone by oropharyngeal aspiration with a single dose repeated weekly for 90 days. We observed DNA double-strand breaks increased in a concentration-dependent manner, but homologous recombination repair decreased in rat lungs after 90 days of exposure. Notably, these effects were more pronounced in bronchioles than alveoli. We also considered these effects in Cr(VI)-associated human lung tumors and observed increased DNA double-strand breaks and reduced RAD51 levels in lung tumor tissue compared with adjacent normal lung tissue. Thus, Cr(VI)-induced induction of DNA double-strand breaks, and inhibition of homologous recombination repair translates from cultured cells to experimental animals, normal lung tissue adjacent to the tumor, and Cr(VI)-associated human lung tumors.


Intraoperative Transbronchial Metallic Coil Marking for Small Peripheral Pulmonary Lesions in a Hybrid Operation Room

: Computed tomography (CT)-guided transbronchial metallic coil marking is useful for identifying the locations of small peripheral pulmonary lesions. Even deeply located lesions may be accurately identified and resected with adequate margins. This method is also applicable to multiple lesions. The present study examined the efficacy of our marking method using cone-beam CT (CBCT) under general anesthesia in a hybrid operation room. : In the hybrid operation room, an ultrathin bronchoscope was inserted into the objective bronchus under virtual bronchoscopic navigation, and a metallic coil was installed under CBCT guidance. The lesion was then resected with wedge resection by single- or 3-port video-assisted thoracoscopic surgery under fluorescence guidance. Eighty-seven patients with 90 lesions were treated between October 2016 and December 2022. The median lesion size was 11 mm and the median distance from the pleural surface was 8.7 mm. Lesions comprised 19 pure ground-glass nodule (GGN), 35 partly solid, and 36 solid types. : All lesions were visualized by CBCT, and metallic coils were installed into the objective bronchi. The median distance from lesions to coils was 3.6 mm, and the median marking time was 23.5 min. All lesions were resected with sufficient margins. In total, 57 lesions were diagnosed as primary lung cancer, 26 as metastatic lung tumors, 3 as nodular lymphoid hyperplasia, and 4 as others. There were no complications associated with the marking procedure. : CBCT represents an alternative modality for identifying peripheral lung lesions due to its ability to visualize even small GGNs. It is a minimally invasive technique because the treatment sequence is completed under general anesthesia with the same quality as previous methods performed in a CT-equipped interventional radiology suite.


Intraoperative transbronchial metallic coil marking guided by mobile 3D C-arm for resection of a small peripheral lung lesion

Sublober resection of small peripheral lung lesions using video-assisted thoracoscopic surgery may require marking and confirmation using 3D imaging in the interventional radiology suite or in the hybrid operating room (HOR) before surgery is started. We report a novel approach for intraoperative transbronchial metallic coil marking followed by thoracoscopic wedge resection in a conventional operating room under mobile 3D C-arm guidance. Under general anesthesia, an ultrathin video-bronchoscope was inserted into an objective bronchus guided with virtual bronchoscopic navigation, and a coil-feeding microcatheter was introduced through the bronchoscope's channel. After the position of the catheter tip was confirmed with cone-beam computed tomography (CT) images rendered via a mobile 3D C-arm, a metallic coil was subsequently deployed through the catheter as a marker. During surgery, the nodule with the metallic coil was grasped with pulmonary forceps and fully resected with endostaplers under fluoroscopic guidance. This method has advantages because the transbronchial approach carries a lower risk of complications such as pneumothorax and air embolism compared with a percutaneous approach, and the metallic coil provides more accurate, pinpoint localization compared with liquid dye. Mobile 3D C-arm-guided transbronchial metallic coil marking followed by thoracoscopic wedge resection under fluoroscopic guidance is a one-stop solution for intraoperative marking and resection of small peripheral pulmonary lesions in any operating room.


Lenvatinib treatment strategy for thyroid carcinoma with malignant pleurisy: a case report

Although lenvatinib is effective for unresectable thyroid carcinoma, it may cause adverse events owing to rapid tumor shrinkage or necrosis. Pneumothorax during lenvatinib therapy is rare. However, once it occurs, it can become a refractory and fatal complication. Herein, we report two cases of thyroid carcinoma with malignant pleurisy treated with lenvatinib and discuss treatment strategies to prevent pneumothorax. The first case involved a 78-year-old male with papillary thyroid carcinoma and malignant bilateral pleural effusion. He underwent pleurodesis with talc for the left pleural effusion due to respiratory distress, and lenvatinib therapy was initiated. Forty days after lenvatinib therapy, the patient developed a right pneumothorax and underwent surgery for a prolonged air leak. However, the left pneumothorax was prevented by pleurodesis. During surgery, the visceral pleura was fragile, and repair of the pulmonary fistula was difficult. Pathological examination revealed an anaplastic carcinoma in the visceral pleura. The air leak disappeared 20 days after surgery; however, the patient died 22 days after surgery due to progression of the underlying disease. The second case involved a 65-year-old female with a poorly differentiated thyroid carcinoma and lung metastasis. She underwent ablation with 30 mCi I after total thyroidectomy, and there was no accumulation in the metastatic sites. Chest computed tomography (CT) revealed the progression of malignant pleurisy in the right thoracic cavity, and iodine-resistant disease was confirmed. She was treated with lenvatinib after talc pleurodesis and showed good progress without any adverse events. The presence of malignant pleurisy results in a risk of developing lenvatinib-associated pneumothorax. Therefore, pleurodesis should be considered before lenvatinib therapy for thyroid carcinomas with malignant pleurisy.


Impact of interstitial lung disease gender-age-physiology index in surgically treated lung cancer

The postoperative prognosis of patients with interstitial lung disease (ILD) and lung cancer is poor. Recently, the ILD-gender-age-physiology (GAP) index was identified as a clinical prognostic factor for patients with ILD. This study investigated the ILD-GAP index and oncological factors regarding postoperative outcomes. We retrospectively reviewed 87 lung cancer patients with comorbid ILD who underwent curative resection at our institution between April 2005 and December 2019. Short-term postoperative outcomes and overall survival (OS) based on the ILD-GAP index were examined. OS rates after surgery were calculated using the Kaplan-Meier method, and group differences were analyzed using the Log-Rank test. Univariate and multivariate analyses for OS were performed using the Cox regression model. Multivariate analyses revealed ILD-GAP index ≥ 4 [Hazard ratio, 3.349; 95% confidence interval 1.375-8.155; P = 0.008] as a factor associated with OS. In the ILD-GAP index ≥ 4 group, no deaths occurred from primary lung cancer, with respiratory-related deaths being the most common, and exacerbation of ILD was more frequent (P = 0.007). Regarding perioperative results, a significant difference was observed in 90-day mortality (2.7% vs. 23.0% [P = 0.022]), and more patients required home oxygen therapy (14.9% vs. 69.2% [P < 0.001]) in the ILD-GAP index ≥ 4 group. An ILD-GAP index ≥ 4 indicated a poor prognostic factor for patients with surgically treated lung cancer. Careful consideration of surgical indications is essential for patients with an ILD-GAP index ≥ 4.

International Journal of Clinical Oncology


DNA methylation and mRNA expression of ZNF577 as biomarkers for the detection and prognosis of lung adenocarcinoma.

Despite advances in science and technology, lung cancer remains a major public health issue. The discovery of early diagnostic and prognostic markers is still needed to reduce the mortality rate of lung cancer, which is the highest among all cancer types. Aberrations in the DNA methylation system have an important role in human cancer and are promising for the development of early diagnostic and prognostic markers. The present study focused on zinc finger protein (ZNF)577, whose encoding gene was indicated to exhibit promoter hypermethylation together with 9 other genes in lung adenocarcinoma (LADC) in a previous study by our group. ZN577 is a member of the ZNG family and its functional role has so far remained elusive. LADC tissue samples surgically resected at Tokushima University Hospital (Tokushima, Japan) between April 1999 and November 2013 were collected. A total of 73 tumors and 27 paired tumor-adjacent normal tissues were examined for DNA methylation and mRNA expression of ZNF577. A total of 149 LADC tissue samples were collected and evaluated by immunohistochemistry (IHC) for the tissue expression of ZNF577. High methylation (n=27, P<0.0001) and low mRNA expression levels (n=27, P<0.031) of ZNF577 were identified in LADC tissues, and it was demonstrated that methylation levels were inversely correlated with mRNA expression levels (P=0.0116, =-0.2515). Among the LADC tissues, lepidic-patterned samples had lower methylation levels of ZNF577 than other pathological types. In addition, mRNA expression levels of ZNF577 were significantly higher in females, non-smokers and stage I samples. Overall survival [P<0.0001; area under curve (AUC)=0.8658] and disease-free survival (DFS; P<0.0004; AUC=0.7232) rates were significantly higher in the ZNF577 high mRNA expression group than in the ZNF577 low mRNA expression group. Among the 149 LADC samples examined by IHC, 105 were negative and 44 were positive for the tissue expression of ZNF577. Cox regression analysis showed poorer DFS (hazard ratio: 3.917; P=0.023) in patients with lower expression of ZNF577. In conclusion, higher methylation levels of ZNF577 were observed in LADC tissues than in normal lung tissue and low mRNA expression of ZNF577 was associated with unfavorable prognosis.


Investigating the usefulness of functional assessment of the elderly for lung cancer patients undergoing surgical treatment

外科治療を受ける肺がん患者に対する高齢者機能評価の有用性の検討


Surgical outcomes of video-assisted neck surgery for papillary thyroid carcinoma

New approaches to endoscopic thyroid surgery have been developed to improve cosmetic results, one of which is video-assisted neck surgery (VANS). The present study investigates the safety and effectiveness of thyroidectomy by VANS as oncologic surgery for papillary thyroid carcinoma (PTC). The subjects of this retrospective study were 121 patients with PTC, who underwent hemi-thyroid lobectomy and central lymph node dissection via open surgery (n = 102) or VANS (n = 19) at Tokushima University Hospital between 2011 and 2023. We performed 1:1 propensity score matching and then compared the surgical outcomes between the two matched groups. Propensity score matching generated 18 distinct examination pairs. The VANS group had significantly less blood loss (P = 0.003), but a longer operative time (P < 0.001) than the open thyroidectomy group. There were two cases of transient recurrent laryngeal nerve paralysis and one case of recurrence in the lateral regional lymph nodes in the VANS group. However, no significant differences were observed in the incidence of complications (P = 0.243) or recurrence (P = 0.500) between the two groups. VANS is a safe and effective surgical procedure for PTC, but longer follow-up is needed to assess tumor recurrence.


Robot-assisted thoracoscopic resection of a posterior mediastinal tumor with immunoglobulin G4-related disease: a case report

Immunoglobulin (Ig)G4-related disease affects nearly every organ, and its clinical course varies depending on the involved organ; however, its occurrence in the mediastinum is rarely reported. A 58-year-old woman presented with a posterior mediastinal tumor along the thoracic spine on imaging. Based on her elevated serum IgG4 level of 349.7 mg/dL, IgG4-related disease was suspected. Since the tumor was growing and malignancy could not be excluded, surgical resection was performed for definitive diagnosis. Robot-assisted thoracoscopic surgery was performed via the left semipronation and right thoracic approaches. The irregularly-shaped tumor was located on the level of the seventh to ninth thoracic vertebra, along the sympathetic nerve. A malignancy was not excluded based on the appearance of the tumor. The tumor had poor mobility. The sympathetic nerves, intercostal arteries, and veins were also excised. In this case, the articulated forceps, used during the robotic surgery, were useful in achieving complete tumor resection along the vertebral body. The pathological examination revealed IgG4-positive plasma infiltration, which fulfilled the criteria for IgG4-related diseases. The postoperative course was uneventful, and the patient underwent follow-up on an outpatient basis without additional medications. The clinical presentation of IgG4-related disease varies, based on the involved organs. This case was rare because the mediastinum was involved, and it emphasized the effectiveness of surgical resection.


Silicone stent placement for tracheal stenosis induced by a giant goiter due to Graves disease: a case report

Although thyroid tumors with tracheal stenosis are occasionally encountered, severe tracheal stenosis caused by benign thyroid tumors is rare. We herein describe a case in which a silicone tracheal stent was placed for severe tracheal stenosis induced by a giant goiter due to Graves' disease. A 93-year-old woman had been receiving thiamazole treatment for Graves' disease with a thyroid goiter for 32 years. She emergently presented to the hospital with sudden difficulty breathing and the temporary loss of consciousness. Although marked stridor was heard, the patient's respiratory status was stable in the first visit. Computed tomography revealed a giant thyroid goiter that extended to the mediastinum. The trachea was compressed by the sternal notch and thyroid gland, resulting in severe stenosis, and the tracheal lumen was only 1 mm. Surgical thyroidectomy was expected to be difficult due to the high risk of complications associated with the large size of the goiter and advanced age of the patient. Therefore, we decided to place a tracheal stent. A silicone stent (Dumon tube) was inserted into the site of tracheal stenosis under general anesthesia. After stent placement, respiratory distress symptoms improved, and no complications were observed. Three months after stent placement, the stent opening side was narrowed due to defective granulation and, thus, was cauterized with argon plasma coagulation. We encountered a patient who was treated by tracheal silicone stent placement for severe tracheal stenosis induced by a giant goiter due to Graves' disease. A silicone stent effectively secures the airway for benign thyroid tumors that cause severe airway stenosis.


Dual indocyanine green fluorescence imaging for segmentectomy in pulmonary metastasis of hepatocellular carcinoma : a case report


Long-term outcomes of S-1 combined with low-dose docetaxel as neoadjuvant chemotherapy (N-1 study, phase II trial) in patients with operable breast cancer

We previously reported that S-1 and low-dose docetaxel (DOC) (N-1 study, phase II trial) could be a well-tolerated and effective neoadjuvant chemotherapies (NACs) for patients with operable breast cancer. Herein, we analyzed the long-term outcomes and developed clinicopathological and molecular predictors of pathological complete response (pCR). Eighty-three patients received S-1 (40 mg/m orally on days 1-14) and DOC (40 mg/m intravenously on day 1) every 3 weeks for 4 to 8 cycles. Disease-free survival (DFS) and overall survival (OS) were analyzed for each population with a pCR status. To assess the relationship between pCR and clinicopathological factors such as tumor-infiltrating lymphocytes (TILs, 1+ <10%, 2+ 10%-50%, and 3+ >50%) and nuclear grade (NG), microarray was used to compare the microRNA profiles of the pCR and non-pCR groups using core needle biopsy specimens. With a median follow-up duration of 99.0 (range, 9.0-129.0) months, the 5-year DFS and OS rates were 80.7% and 90.9%, respectively. The 5-year OS rate of the pCR group was significantly better than that of the non-pCR group (100% vs. 86.2%, p = .0176). Specifically, in triple-negative patients, the difference was significant (100% vs. 60.0%, p = .0224). Multivariate analysis revealed that high TILs (≥2-3+) and NG 2-3 independently predicted pCR. Microarray data revealed that 3 miRNAs (miR-215-5p, miR-196a-5p, and miR-196b-5p) were significantly upregulated in the pCR group. Our NAC regimen achieved favorable long-term outcomes and significantly improved OS in the pCR group. High TILs, NG 2-3, and some miRNAs may be predictors of pCR.


Aberrant DNA Methylation of NPTX2 as an Indicator of Malignant Behavior in Thymic Epithelial Tumors

Thymic epithelial tumors (TET) consist of thymomas, thymic carcinoma (TC), and neuroendocrine tumors of the thymus (NECTT). Genetic and epigenetic alterations in TET have been the focus of recent research. In the present study, genome-wide screening was performed on aberrantly methylated CpG islands in TET, and this identified neuronal pentraxin 2 (NTPX2) as a significantly hypermethylated CpG island in TC relative to thymomas. NPTX2 is released from pre-synaptic cells in response to neuronal activity/seizure, and plays a role in host immunity and acute inflammation. TET samples were obtained from 38 thymomas, 25 TC, and 6 NECTT. The DNA methylation, mRNA, and protein expression levels of were examined. The DNA methylation rate of the gene was significantly higher in TC than in the normal thymus and thymomas, except B3. The mRNA expression level of was lower in TC than in the normal thymus. An inverse relationship was observed between mRNA expression levels and methylation levels. Relapse-free survival was shorter in patients with high DNA methylation levels than in those with low DNA methylation levels. NECTT showed very high mRNA and protein expression levels and low DNA methylation levels of NPTX2. NPTX2 may function as a tumor suppressor in TC, and have an oncogenic function in NECTT.


Achievements of perioperative assist team medical care in esophageal cancer surgery, Tokushima University Hospital

Radical esophagectomy is highly invasive and associated with many postoperative complications. A decline in postoperative QOL is a serious issue for patients, and comprehensive perioperative management through multidisciplinary cooperation is necessary. Our institution has established a perioperative assist team (OPERA) to address this need since 2017. This study included 109 patients with esophageal cancer who underwent neoadjuvant chemotherapy and esophagectomy from 2009 to 2018. O group, means OPERA intervention group, included 57 patients, and N group, means Non-OPERA intervention group, included 52 patients. The effects of the OPERA intervention on reducing chemotherapy-related adverse events and improving postoperative outcomes were retrospectively investigated. The OPERA intervention significantly reduced the incidence of chemotherapy-related adverse events (P=0.002). In particular, anorexia and diarrhea, febrile neutropenia were significantly reduced (P<0.001, P=0.002, P=0.025, respectively). Postoperatively, the start date of walking was significantly earlier (P<0.001), the incidence of pneumonia was lower (P=0.022). At the time of postoperative discharge, N group was significantly greater weight loss compared to O group (P=0.002). The 5-year survival rate was longer in O group (P=0.003). The OPERA intervention reduced the incidence of chemotherapy-related adverse events and postoperative complications and helped improved prognosis. J. Med. Invest. 71 : 279-285, August, 2024.

The Journal of Medical Investigation : JMI


A case of severe interstitial lung disease developed during administration of abemaciclib but successfully rescued

アベマシクリブ投与中に重篤な間質性肺疾患をきたしたが救命しえた1例


Lung regeneration with rat fetal lung implantation and promotion of alveolar stem cell differentiation by corticosteroids

The lung is a difficult organ to regenerate, and the development of functional lungs has still not been achieved. In this study, we investigated lung regeneration using a rat fetal lung tissue-implanted model. This study aimed to evaluate the functioning of the implanted fetal lung tissue and investigate the graft differentiation and maturation mechanism, focusing on alveolar stem cells. Fetal lung tissue fragments were obtained from Lewis rats on day 17 and implanted into adult lungs. Animals were divided into the following three groups: group 1, injection into the adult left lung parenchyma; group 2, injection with post-caval lobectomy; and group 3, injection with post-caval lobectomy and corticosteroid administration. Computed tomography was performed on weeks 1, 2, 4, and 8. The presence of alveolar pore, CD31 expression, and bipotential progenitor cell (podoplanin+/surfactant protein C+) localization were histologically evaluated. MiRNA expression was comprehensively compared among the three groups. The grafts comprised type I and type II alveolar cells connected to the recipient lungs with alveolar pores and capillary networks in the interstitial tissue. The alveolar space was the largest and the computed tomography value was the lowest in the grafts of the corticosteroid-administered group. The number of bipotential progenitor cells was the lowest in the corticosteroid administration group on day 7. Moreover, microRNA-487-3p, 374-5p, and 20b-5p expression was changed by more than 2-fold between the post-caval lobectomy and corticosteroid administration groups. Implanted fetal lung tissues established airway and capillary communication with the recipient lungs, and corticosteroids accelerated their maturation by promoting the differentiation of progenitor cells. The study findings provide new insights into lung regeneration research.


Effectiveness of surveillance by echocardiography for Cancer therapeutics-related cardiac dysfunction of patients with breast Cancer

Cancer therapeutics-related cardiac dysfunction (CTRCD) affect the prognosis of patients with breast cancer. Echocardiographic surveillance of patients treated with anti-human epidermal growth factor receptor type 2 (HER2) antibodies has been recommended, but few reports have provided evidence on patients with breast cancer only. We aimed to evaluate the effectiveness of echocardiographic surveillance for breast cancer patients. We identified 250 patients with breast cancer who were treated with anti-HER2 antibodies from July 2007 to September 2021. We divided 48 patients with echocardiographic surveillance every 3 months into the surveillance group and 202 patients without echocardiographic surveillance into the non-surveillance group. In the surveillance group, patients with a considerable reduction in global longitudinal strain of 15 % were considered for the initiation of cardioprotective drugs. The composite outcome of CTRCD and acute heart failure was the study endpoint. The mean age was 59 ± 12 years. During the follow-up period of 15 months (12-17 months), 12 patients reached the endpoint. The surveillance group had significantly lower incidence of the composite outcome (2.1 % vs. 5.5 %, adjusted odds ratio: 0.28, 95 % confidential intervals: 0.09-0.94; p = 0.039) and higher rates of prescriptions of cardioprotective drugs than the non-surveillance group. The incidence of cardiac complications was significantly lower in the surveillance group than the non-surveillance group, which supports the effectiveness of echocardiographic surveillance in patients with breast cancer.


Assessment of dyspnea, ADL, and QOL in the perioperative period in lung cancer patients treated with minimally invasive surgery

Patients with lung cancer generally undergo minimally invasive surgery, such as video-assisted thoracoscopic surgery (VATS). This study examined the changes in health conditions and symptoms of patients with lung cancer using the European Organization for Research and Treatment of Cancer-Quality of Life Questionnaire (EORTC QLQ) C-30 questionnaires after surgery. This was a longitudinal descriptive study. One hundred and three patients with lung cancer who underwent lung resection at Tokushima University Hospital between 2012 and 2021 were eligible. They completed EORTC QLQ-C30, QLQ-LC13, the Cancer Dyspnea scale (CDS), and pulmonary-ADL (P-ADL) before and 1, 3, and 6 months after surgery. Regarding functional scale scores, impairments in physical and role functions persisted for 6 months after surgery. In symptom scale scores, fatigue, pain, dyspnea, and appetite loss continued for 6 months after surgery. In CDS, sense of effort, discomfort, and total dyspnea scale scores were elevated for 6 months after surgery. In P-ADL, most ADL were impaired 1 month after surgery, but recovered by 3 months. The dyspnea index of ADL was lower for 6 months after surgery. Impairments in health conditions and symptoms persisted for 6 months after surgery despite its minimally invasive nature. J. Med. Invest. 70 : 388-402, August, 2023.


Absolute Lymphocyte Count Changes During Neoadjuvant Chemotherapy are Associated With Prognosis of Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer Patients

Some reports have shown that absolute lymphocyte count (ALC) is associated with prognosis in breast cancer; however, the impact of ALC changes remains unclear. This study aimed to investigate the relationship between ALC changes during neoadjuvant chemotherapy for human epidermal growth factor receptor-2 (HER2)-positive breast cancer patients and disease prognosis. This retrospective cohort study January 2010 to September 2020) included patients diagnosed with HER2-positive breast cancer and treated with trastuzumab-based neoadjuvant chemotherapy. The ALC ratio was defined as the ALC value after administration of the anti-HER2 drug divided by the ALC value before administration. The optimal ALC ratio cut-off value was identified using the receiver operating characteristic curve analysis and Youden's index. The relationship between the ALC ratio and disease-free survival was assessed using the Kaplan-Meier method. Univariate and multivariate analyses were performed using the Cox proportional hazards model. Data from a total of 100 HER2-positive breast cancer patients were analyzed. The cut-off value of the ALC ratio was set as 1.142. The median follow-up period was 52.0 (range: 5.1-123.7) months. The 5-year disease-free survival rates were 88.4% and 60.9% in the high-and low-ALC ratio groups, respectively, and were significantly higher in the high-ALC ratio group (p = .0031). The ALC ratio was an independent prognostic factor in multivariate Cox proportional hazards analysis (p = .0032). HER2-positive breast cancer patients with a higher ALC ratio during trastuzumab-based neoadjuvant chemotherapy may have a better prognosis than their counterparts.


Aberrant methylation of dipeptidyl peptidaselike 6 as a potential prognostic biomarker for lung adenocarcinoma

We previously performed the genome-wide screening of aberrantly methylated CpG islands (CGIs) using the paired tumorous and non-tumorous tissues of 12 lung adenocarcinomas (LADC). In comparisons with paired normal lung tissues, dipeptidyl peptidase-like 6 () has been identified as the most significantly hypermethylated CGI in LADC. is a protein that modulates A-type potassium channels in the somatodendritic compartments of neurons, which play a role in synaptic plasticity. Previous studies have showed that is downregulated in cancers, such as acute myeloid leukemia and melanoma, but upregulated in colon cancer, which is attributed to hyper- and hypomethylation, respectively. The present study investigated the methylation and expression levels of and its prognostic value in patients with LADC. The DNA methylation and mRNA expression levels of in surgically resected LADC tissues were examined by bisulfite pyrosequencing and reverse transcription-quantitative PCR, respectively. The DNA methylation and mRNA expression levels of were both significantly higher in LADC tissues compared with in normal lung tissues (n=25; P<0.0001). Overall and disease-free survival rates were significantly higher in LADC with high mRNA expression levels compared with those with low levels. In conclusion, epigenetic alterations in were significantly higher in LADC tissues compared with in normal lung tissues, which may contribute to the malignant features and worse prognosis of these patients.


Cone-beam computed tomography-guided endobronchial ultrasound using an ultrathin bronchoscope for diagnosis of peripheral pulmonary lesions: a prospective pilot study

Multimodal transbronchial biopsy (TBB) may have improved diagnostic yield for peripheral pulmonary lesions suspected as lung cancer. Radial endobronchial ultrasound (R-EBUS) provides real-time imaging and confirmation of the location of the lesions. Cone-beam computed tomography (CBCT) can confirm that the forceps tip has reached the lesion before biopsy. Patients with peripheral pulmonary lesions and a positive computed tomography (CT) bronchus sign (based on slice thickness of 1 mm) were prospectively enrolled. An ultrathin bronchoscope (UTB) and R-EBUS probe were advanced to the target bronchus. Thereafter, forceps were advanced, and CBCT was performed. R-EBUS was performed for re-navigation, if possible. The obtained EBUS and CBCT images were classified into "within" (type 1), "adjacent to" (type 2), or "far from" (type 3), based on the probe or forceps tip. For 20 lesions, the diagnostic yield was 85%. The primary EBUS images were of types 1, 2, and 3 in 12, 6, and 2 cases, respectively. The primary CBCT images were of types 1, 2, and 3 in 12, 6, and 2 cases, respectively. Primary EBUS and CBCT image types were equivalent in 14 cases. Of the 12 cases with type 1 primary EBUS image, 9 cases had a type 1 primary CBCT image, while 3 cases exhibited positional misalignment of the forceps tip. Re-navigation was required in 8 cases with types 2 and 3 primary CBCT images. CBCT-guided TBB using an UTB and EBUS may enable real-time positioning guidance and better re-navigation in the diagnosis of peripheral pulmonary lesions.


Abscopal effect in a patient with solitary extramedullary plasmacytoma of the thyroid: case report

The abscopal effect is a systemic antitumor response that occurs distant to the irradiation site and is induced by local irradiation. We herein describe a case of solitary extramedullary plasmacytoma (SEP) of the thyroid in which bone metastases disappeared after thyroidectomy and cervical radiotherapy (RT). A 68-year-old man with a right cervical swelling for approximately 10 years visited a hospital with left elbow pain that persisted for 5 months. He was referred to our hospital for more detailed examinations and treatment. An immobile mass of approximately 10 cm in diameter was palpable on the right side of the patient's neck. Computed tomography (CT) showed osteolytic changes in the left humerus and right scapula, and a tumor in the right lobe of the thyroid gland. The patient was diagnosed with widely invasive follicular carcinoma and multiple bone metastases and underwent total thyroidectomy. During surgery, tumor infiltration into the trachea was observed. Shaving between the tumor and trachea was performed. Based on the results of a pathological examination, the patient was diagnosed with primary extramedullary plasmacytoma of the thyroid. After surgery, external beam RT was performed on the neck, which also reduced the pain in the left elbow. Positron emission tomography (PET)-CT showed the decreased accumulation of fluorodeoxyglucose (FDG) in the left humerus and right scapula, and the amelioration of osteolytic changes on CT. SEP of the thyroid is rare, and to the best of our knowledge, this is the first case report in which the abscopal effect was observed after thyroidectomy and cervical RT.


F-FDG PET/CT Showing Rare Mediastinal Growing Teratoma Syndrome Following Chemotherapy.

Molecular Imaging and Radionuclide Therapy


A case of papillary thyroid carcinoma with renal and pulmonary metastases

Distant metastases derived from papillary carcinoma are generally detected in the lungs and bones. However, renal metastasis is rare. We herein report a case of papillary thyroid carcinoma with renal and pulmonary metastases that had been initially diagnosed as primary renal carcinoma with pulmonary metastases. The lesions showed response to immune checkpoint inhibitors and tyrosine kinase inhibitor but not to radioactive iodine therapy.


Axillary lymphangioma that developed following COVID-19 vaccination: a case report

Extensive vaccination programs are being implemented worldwide for coronavirus disease 2019 (COVID-19). With the spread of vaccination, swelling of the lymph nodes after vaccination is frequently seen. We encountered a patient who developed left axillary lymphadenoma following vaccine administration. The patient was a Japanese woman in her 80 s who had previously undergone surgery for right breast cancer. She received two injections of the Pfizer-BioNTech COVID-19 vaccine in her left arm. Approximately 3 months later, she complained of left axillary swelling, and imaging resulted in a diagnosis of left axillary lymphangioma. In accordance with the patient's wishes, we performed axillary mass resection. The pathological diagnosis was lymphangioma. Our examination findings indicated that congestion of the axillary lymph vessels might have been caused by upper-arm injections of the COVID-19 vaccine.


Diversity of lymphatic flow in patients with lung cancer revealed by computed tomography lymphography

This study was conducted to verify the optimal extent of lymph node dissection or sampling during lung cancer surgery based on the sentinel node (SN) map created by computed tomography (CT) lymphography. From April 2010 to January 2015, patients with clinical stage I non-small-cell lung cancer, who were candidates for lobectomy or segmentectomy with standard hilar and mediastinal lymph node dissection, and in whom bronchus reached the tumour, were enrolled. An ultrathin bronchoscope was inserted to the target bronchus under the guidance of virtual bronchoscopic navigation images. CT images of the chest were obtained 30 s after 2.5 ml of iopamidol was injected. SNs were identified when the maximum CT attenuation value of the lymph nodes on postcontrast CT images increased by 30 Hounsfield units or more compared with the precontrast images. Patients underwent lobectomy with standard lymph node dissection. SNs were identified in 36 (87.8%) of the 41 patients. The average number of SNs was 1.6 (range, 1-4). There was 1 false negative case; therefore, the accuracy of SN identification was 97.2% (35/36). In 5 (13.9%) of 36 patients, SNs were outside the lobe-specific lymph node station range (#11i from right S1, #7 from right S1, #4R from right S8, #12u from right S8, #7 and #12l from left S1 + 2). CT lymphography demonstrated the diversity of lymphatic spreading patterns and there were cases in which lymph flows are found outside the lymph node dissection range.

Interactive Cardiovascular and Thoracic Surgery


XB130 deficiency causes congenital hypothyroidism in mice due to disorganized apical membrane structure and function of thyrocytes

Congenital hypothyroidism is often caused by genetic mutations that impair thyroid hormone (TH) production, resulting in growth and development defects. XB130 (actin filament associated protein 1 like 2) is an adaptor/scaffold protein that plays important roles in cell proliferation, migration, intracellular signal transduction, and tumorigenesis. It is highly expressed in thyrocytes, however, its function in the thyroid remains largely unexplored. mice and their littermates were studied. Postnatal growth and growth hormone levels were measured, and responses to low or high-iodine diet, and levothyroxine treatment were examined. TH and thyrotropin in the serum and TH in the thyroid glands were quantified. Structure and function of thyrocytes in embryos and postnatal life were studied with histology, immunohistochemistry, immunofluorescence staining, Western blotting, and quantitative reverse transcription polymerase chain reaction. mice exhibited transient growth retardation postnatally, due to congenital hypothyroidism with reduced TH synthesis and secretion, which could be rescued by exogenous thyroxine supplementation. The thyroid glands of mice displayed diminished thyroglobulin iodination and release at both embryonic and early postnatal stages. XB130 was found mainly on the apical membrane of thyroid follicles. Thyroid glands of embryonic and postnatal mice exhibited disorganized apical membrane structure, delayed folliculogenesis, and abnormal formation of thyroid follicle lumina. XB130 critically regulates folliculogenesis by maintaining apical membrane structure and function of thyrocytes, and its deficiency leads to congenital hypothyroidism.


GHSR methylation-dependent expression of a variant ligand and receptor of the ghrelin system induces thymoma tumorigenesis

Our previous study reported that the DNA methylation of growth hormone secretagogue receptor () was significantly higher in thymoma or thymic carcinoma (TC) than in normal thymic tissue samples. Thymic epithelial tumors (TETs) with higher DNA methylation were associated with significantly worse prognosis than those with lower levels of DNA methylation. Diversified components of the ghrelin- axis may exert opposing effects in cancer progression, depending on the cancer type in question. However, the precise function of the axis remains unclear. In the present study, the mRNA expression of five key components of the ghrelin system [native ligand ghrelin, variant ligand In-1 ghrelin, native receptor GHSR1a, variant receptor GHSR1b and acylation enzyme ghrelin O-acyltransferase (GOAT)] were examined in 58 TET samples by reverse transcription-quantitative PCR, and protein expression of GHSR1a and GHSR1b was assessed in 20 TETs using immunohistochemistry. The results revealed that In-1 ghrelin, GHSR1b (variant forms) and GOAT were more strongly expressed in thymoma compared with thymic-adjacent tissue. By contrast, no significant differences were observed in the expression of ghrelin and GHSR1a (native forms) between thymoma and thymic tissue. The mRNA expression of In-1 ghrelin and GHSR1b (variant forms) was positively associated with methylation in thymoma tissue samples. However, a relationship was not found between ghrelin, GHSR1a or GOAT expression (native forms) and methylation in thymoma. Immunohistochemical analysis revealed that mRNA expression of GHSR1a and GHSR1b generally correlated with expression of the corresponding protein, and that the expression of GHSR1b was increased in advanced-stage TETs. These results indicate that the DNA methylation of is associated with a shift from native expression (ghrelin and GHSR1a) to variant expression (In-1 ghrelin and GHSR1b), which induces the tumorigenesis of thymoma, but not TC.


HER2陽性乳癌患者における術前化学療法開始前の総リンパ球数は予後予測の指標となり得る

Purpose : Several studies have shown that peripheral hematologic parameters, such as the absolute lymphocyte count(ALC)and neutrophil to lymphocyte ratio(NLR)can predict the prognosis for malignant tumor. We investigated the relation of these parameter and prognosis before neoadjuvant chemotherapy for human epidermal growth factor receptor-2(HER2)-positive breast cancer patients. Methods : From April 2009 to March 2019, 85 patients diagnosed with HER2‐positive breast cancer and treated with trastuzumab-based neoadjuvant chemotherapy were included in this retrospective cohort study. The optimal cut-off for the NLR and ALC was identified using the receiver operating characteristic(ROC)curve analysis and Youden's index. Results : The median age of patients at the start of treatment was 58．9(range 32‐81)years. The median follow-up time for HER2-positive breast cancer patients was 52．0(range:9．8‐114．3)months. In this period, 11 patients developed recurrence. The low-ALC group showed better disease free survival than the high-ALC group(p=0．0482). There was no significant difference in disease free survival between the low- and high-NLR groups. Conclusion : ALC before neoadjuvant chemotherapy may be a predictor of prolonged disease free survival in HER2‐positive breast cancer patients.


Hypervascularized bronchial arteries as a risk factor for intraoperative bleeding and prolonged surgery

The present study investigated whether highly vascularized bronchial arteries affect the intraoperative blood loss and the operative time of video-assisted thoracic surgery (VATS) lobectomy for patients with non-small cell lung cancer. We retrospectively collected data on consecutive pathological stage I to IIIA non-small cell lung cancer patients who underwent VATS lobectomy with systematic lymph node dissection between January 2017 and December 2019. Patients were divided into the following two groups according to bronchial artery diameters on preoperative enhanced contrast computed tomography (CT) findings: ≤2 and >2 mm groups. Among the 175 patients enrolled, risk factors for intraoperative blood loss >50 mL were being male (P=0.005), a history of smoking (P=0.01), percent forced expiratory volume in 1 s (FEV1.0%) <70% (P=0.012), squamous cell carcinoma (P=0.049), and a bronchial artery diameter >2.0 mm (P<0.001) in the unadjusted analysis, and a bronchial artery diameter >2.0 mm (P<0.001) in the multivariable analysis. Risk factors for an operative time >200 min were being male (P<0.001), a history of smoking (P=0.007), FEV1.0% <70% (P=0.011), squamous cell carcinoma (P=0.046), a bronchial artery diameter >2.0 mm (P<0.001), and experience of surgeon <10 years (P=0.011) in the unadjusted analysis, and being male (P=0.047), a bronchial artery diameter >2.0 mm (P=0.024), and experience of surgeon <10 years (P=0.047) in the multivariable analysis. Bronchial artery diameter was the most important risk factor of intraoperative bleeding and prolonged operative time during VATS lobectomy.


Diagnosis of visceral pleural invasion using confocal laser endomicroscopy during lung cancer surgery

Visceral pleural invasion (VPI) in lung cancer is a significant prognostic factor; however, it is difficult to diagnose preoperatively or intraoperatively. In this study, we examined the possibility of intraoperative diagnosis of VPI using confocal laser endomicroscopy (CLE). Among patients with primary lung cancer who underwent surgery between April 2018 and August 2019, those in whom the tumor was in contact with the pleura on chest computed tomography and whose pleural changes were intraoperatively confirmed were enrolled in this study. In the 35 patients who underwent lung resection (6 cases with visceral pleural infiltration), the area where pleural change was noted was observed and a short video was recorded using CLE. Based on the video images, three evaluators determined the defect ratio (0%, 25%, 50%, 75%, and 100%) of the autofluorescence-positive structure. The area under the receiver operating characteristic curve was used to evaluate the diagnostic performance for VPI. In 15 cases (3 cases with VPI), a validation study was performed for intraoperative VPI according to the cutoff value of the defect ratio of the autofluorescence-positive structure. The areas under the receiver operating characteristic curve for the defect ratio of the autofluorescence-positive structure were 0.86-0.91 for the three readers. Using defect ratio of autofluorescence-positive structure cutoff of ≥50% as predictor of VPI, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 83.3-100.0%, 57.7-73.1%, 35.3-41.7%, 95.0-100.0%, and 75.0-78.1%, respectively, for the three readers. In the validation study, the sensitivity was 100%, the specificity was 83.3%, and the diagnostic accuracy rate was 86.7%. The diagnosis of VPI through CLE is simple, non-invasive, and has high diagnostic accuracy rates. This method may be applicable for determining surgical procedures.


GAD1 expression and its methylation as indicators of malignant behavior in thymic epithelial tumors

Thymic epithelial tumors (TETs) comprise thymomas and thymic carcinoma (TC). TC has more aggressive features and a poorer prognosis than thymomas. Genetic and epigenetic alterations in thymomas and TC have been investigated in an attempt to identify novel target molecules for TC. In the present study, genome-wide screening was performed on aberrantly methylated CpG islands in thymomas and TC, and the glutamate decarboxylase 1 gene () was identified as the 4th significantly hypermethylated CpG island in TC compared with thymomas. catalyzes the production of γ-aminobutyric acid from L-glutamic acid. expression is abundant in the brain but rare in other tissues, including the thymus. A total of 73 thymomas and 17 TC tissues were obtained from 90 patients who underwent surgery or biopsy at Tokushima University Hospital between 1990 and 2017. DNA methylation was examined by bisulfite pyrosequencing, and the mRNA and protein expression levels of were analyzed using reverse transcription-quantitative PCR and immunohistochemistry, respectively. The DNA methylation levels of were significantly higher in TC tissues than in the normal thymus and thymoma tissues, and methylation exhibited high sensitivity and specificity for discriminating between TC and thymoma. The mRNA and protein expression levels of were significantly higher in TC tissues than in thymomas. Patients with TET with high DNA hypermethylation and high mRNA and protein expression levels had significantly shorter relapse-free survival rates than those with low levels. In conclusion, significantly more epigenetic alterations were observed in TC tissues compared with in thymomas, which may contribute to the clinical features and prognosis of patients.


Endobronchial Ultrasound Improves the Diagnosis of the Tracheobronchial Invasion of Advanced Esophageal Cancer

Accurate diagnosis of the tracheobronchial invasion of advanced esophageal cancer is essential to select appropriate treatment and improve prognosis; however, it is difficult using the conventional modalities. This study aimed to clarify the diagnostic usefulness of convex probe endobronchial ultrasound (CP-EBUS) for the diagnosis of the tracheobronchial invasion of advanced esophageal cancer. We conducted a cadaveric study to clarify the changes in ultrasonic and histopathologic findings in the esophageal tumor and tracheal invasion models. Additionally, we examined CP-EBUS for patients with advanced thoracic esophageal cancer in whom tracheobronchial invasion was suspected on contrast-enhanced computed tomography (CE-CT) scan. We retrospectivity evaluated the diagnosis of CP-EBUS, comparing the pathological findings and treatment outcomes. Cadaveric esophageal tumor and tracheal invasion models showed the disappearance of the third layer observed with CP-EBUS and histologically proven interruption of the adventitia. This indicated that the third layer corresponded with the tracheal adventitia. We examined 40 patients with advanced thoracic esophageal cancer in whom tracheobronchial invasion was suspected. The precise diagnosis was pathologically confirmed in 9 of 14 patients diagnosed with cT3 who underwent radical surgery. 20 of 26 cases diagnosed with cT4b received definitive chemoradiotherapy, and 4 cases received salvage surgery and pathologically confirmed precise diagnosis. CP-EBUS is extremely useful for diagnosing the tracheobronchial invasion of advanced esophageal cancer. It could be an effective modality for determining treatment strategies in cases with a marginal surgical indication.


気管支鏡の破損を分析する

Background. Bronchoscopy is used in many procedures, such as endoscopic ultrasonography, tracheal stent placement, placement of Endobronchial Watanabe Spigots, and preoperative coil marking. However, bronchoscopy is a complicated procedure, and breakage can occur due to external forces. Bronchoscope breakage is associated with both adverse economic effects and patient-related consequences, since these devices are expensive and their breakage may increase the rates of complications and cause interruptions in examinations and treatments, if repairs are necessary. Purpose. We considered the causes of bronchoscope damage at our hospital in order to design future preventive measures and precautions. Method. We examined the bronchoscope type, their breakage status, and the repair costs for the 246 bronchoscopes in our department between January 2015 and November 2017. Result. A bronchoscope was damaged in 3 of the 246 cases, resulting in a damage rate of 1.2%. Damage to the bronchoscope occurred during yttrium-aluminium-garnet laser resection (n=2) because of thermal damage to the suction forceps port, during a right upper lobe biopsy (n=1) because of the forceps contacting the curved part, and during an endobronchial ultrasound lymph node biopsy because of damage to the tube caused by the puncture needle (n=1). Conclusion. All cases of breakage occurred secondary to technical factors owing to a lack of understanding of the structure of the bronchoscope and procedural instability. Bronchoscope damage increases expenses and procedural time while potentially reducing safety. The bronchoscopy procedure must be improved. Furthermore, practitioners should increase their understanding of the bronchoscope structure in order to prevent damage. Precautionary measures can be communicated through short lecture courses and education programs in order to increase practitioners' understanding of the internal structure of the bronchoscope and measures to increase procedural stability.

背景．気管支鏡は超音波内視鏡，ステント，気管支充填術，また当科においては，術前コイルマーキングなど，様々な手技に使用されている．同時に，気管支鏡操作も複雑になり，様々な外力がかかることで破損が起こりやすくなる．気管支鏡の故障は医療経済面での不利益のみならず，合併症発生の増加や，修理期間中の検査・治療が中断されることによる患者側の不利益につながる．目的．当院で経験した気管支鏡の破損について検討し，その原因について探求し，今後の予防策や注意点に関して検討する．方法．2015年1月から2017年11月において当科で気管支鏡検査を施行した246例のうち，気管支鏡修理状況について，気管支鏡の種類や破損原因，修理費などについて検討した．結果．246例中3例(4本)の破損を認め，破損率は1.2%であった．気管内レーザー焼灼術による破損の1例(2本)は，吸引鉗子口の先端の熱損傷による破損であった．生検による破損の1例は湾曲部の鉗子操作によるものであり，超音波気管支鏡の破損の1例は，穿刺針による湾曲部の損傷によるものであった．結論．全例が手技的な要因で発生しており，機器の構造の理解不足や手技の不安定さが原因であった．気管支鏡破損は，経済面や安全面，時間的損失に影響を及ぼす．破損を起こさないためには，手技の向上や気管支鏡構造の理解が必要である．我々が取り組む方策は，気管支鏡内部構造の特性の理解，安定した手技の取得に至る講習，教育を常に意識して実行することである．

The Journal of the Japan Society for Respiratory Endoscopy


Cone-beam computed tomography versus computed tomography-guided ultrathin bronchoscopic diagnosis for peripheral pulmonary lesions: A propensity score-matched analysis

CBCT-guided TBB using a UTB under VBN is a useful method for the diagnosis of peripheral small pulmonary lesions. CBCT-guided TBB using UTB under VBN has been used as an alternative to CT-guided TBB. However, the advantage of CBCT-guided TBB using UTB under VBN over CT-guided TBB is still unknown. This study aimed to compare the diagnostic yield of CT-guided TBB and CBCT-guided TBB using a propensity score-matched analysis. Patients with peripheral pulmonary lesions ≤30 mm were included. Lesions whose bronchus could not be determined by CT were excluded. A UTB and biopsy forceps were advanced to the target bronchus under VBN, 2D-fluoroscopy and CT or CBCT. The CT-guided and CBCT-guided groups were matched for their propensity scores based on patient characteristics. We retrospectively reviewed 93 patients in the CT-guided group and 79 patients in the CBCT-guided group for this study. Furthermore, 48 distinct examination pairs were generated by propensity score matching. In the overall diagnostic yield, the CBCT-guided group showed better results (72.9%) than did the CT-guided group (47.9%) (P = 0.012). The median examination time lasted for 43 (IQR: 37-51) min in the CBCT-guided group and 50 (IQR: 43-62) min in the CT-guided group. The examination time in the CBCT-guided group was significantly shorter than that of the CT-guided group (P = 0.001). CBCT-guided TBB had a better diagnostic yield and shorter examination time than did CT-guided TBB.


Diagnosis of recurrence and follow-up using FDG-PET/CT for postoperative non-small-cell lung cancer patients

There is currently no consensus regarding the best program for postoperative follow-up and surveillance after a curative resection for non-small-cell lung cancer (NSCLC) patients. We examined the diagnostic capability of F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) for detecting recurrence in postoperative NSCLC patients, and we evaluated the results of postoperative surveillance using FDG-PET/CT in asymptomatic patients. Between 2005 and 2013, 496 FDG-PET/CT examinations were performed to detect recurrences for 187 NSCLC patients who had undergone potentially curative operations at our institution. Follow-up FDG-PET/CT was performed ≥ 1 × /year in principle in 172 asymptomatic patients without clinical or radiological evidence of recurrence, and the results were retrospectively reviewed. FDG-PET/CT correctly diagnosed recurrence in 46 of 47 (97.9%) patients and 68 of 69 (98.6%) recurrent sites. The following were obtained: 97.9% sensitivity, 97.1% specificity, 92.0% positive predictive value, 99.3% negative predictive value, and 97.3% accuracy. In six patients, other diseases were detected and treated appropriately. In asymptomatic patients, the detection rate of recurrence in the stage III group was significantly higher than the detection rates in the stage I and II groups, and FDG-PET/CT performed ≤ 3 years post-resection detected significantly more FDG-positive lesions compared to that performed after 4 years. FDG-PET/CT is very useful for detecting recurrence in NSCLC patients after a potentially curative operation. It might be sufficient to perform follow-up FDG-PET/CT until 3 years post-resection for advanced-stage patients. Further randomized clinical trials are needed to determine whether the early detection of recurrences leads to better prognoses.

General Thoracic and Cardiovascular Surgery


Long-term outcomes of sentinel node identification using indocyanine green in patients with lung cancer


Comprehensive Interventions for Building a Better Regional Cooperation for Cancer Patients

より良いがんの地域連携体制構築のための包括的な取り組み

Objectives : We introduce our comprehensive interventions for building a better regional cooperation for cancer patients. Methods : We have made a questionnaire survey for community physicians asking whether they can accept cancer patients and what types of medical treatments they can provide. Based on the questionnaire responses, we visualized the information, developed a new critical pathway, and improved the system in a basic hospital. Results : We first organized the information obtained from the questionnaire responses and uploaded the organized information to the basic hospital's homepage for public access. We then developed a new critical pathway for the cooperation among community physicians considering the prophylactic administration of a granulocyte-colony stimulating factor (G-CSF) formulation for treating cancer patients. This treatment was subsequently applied to four patients. Additionally, a community physician was matched with each patient by a medical social worker during the patients' hospitalization. We improved the basic hospital's simple electronic medical record system to reduce the physicians' workloads. As a result, the document creation could be completed within one minute, and so they could relate to approximately 10 times larger number of cases. Conclusions : Satisfactory cancer treatments can be provided for patients by building the better regional cooperative relationships and dividing the roles with community physicians in an earlier time.

目的:より良いがんの地域連携体制を構築するための包括的な取り組みについて紹介する．方法:かかりつけ医を対象に行った，がん患者の連携の可否と役割分担できる診療内容に関するアンケート結果をもとに，情報の可視化，新たな連携クリティカルパス(連携パス)の導入，拠点病院内の環境整備を行った．結果:まず，アンケート結果の情報を整理し，誰もがアクセスできるよう病院ホームページにアップして可視化した．さらに，予防的G-CSF(Granulocyte-Colony Stimulating Factor)投与連携パスを運用し，少数だが4例に適用した．加えて，入院中に医療ソーシャルワーカーが介入してかかりつけ医を決定し，文書作成を1分以内に完遂できる簡便な電子カルテ運用にして医師の作業負担を減らし，連携件数を約10倍増加させた．結語:より早期から緊密に情報交換し，役割分担することで，患者にとって満足度の高いがん医療を提供できる．今回の取り組みは，より良い連携体制構築に寄与すると考える．


Japanese Journal of Cancer and Chemotherapy


Relationship between regional left ventricular dysfunction and cancer-therapy-related cardiac dysfunction

The aim of our study was to assess the association between risk of cancer-therapy-related cardiac dysfunction (CTRCD) after first follow-up and the difference in echocardiographic measures from baseline to follow-up. We retrospectively enrolled 87 consecutive patients (58±14 years, 55 women) who received anthracycline and underwent echocardiographic examinations both before (baseline) and after initial anthracycline administration (first follow-up). We measured absolute values of global longitudinal strain (GLS), apical longitudinal strain (LS), mid-LS and basal-LS at baseline and first follow-up, and per cent changes (Δ) of these parameters were calculated. Among 61 patients who underwent further echocardiographic examinations (second follow-up, third follow-up, etc), we assessed the association between regional left ventricular (LV) systolic dysfunction from baseline to follow-up and development of CTRCD, defined as LV ejection fraction (LVEF) under 53% and more absolute decrease of 10% from baseline, after first follow-up. LVEF (65%±4% vs 63±4%, p=0.004), GLS (23.2%±2.6% vs 22.2±2.4%, p=0.005) and basal-LS (21.9%±2.5% vs 19.9±2.4%, p<0.001) at first follow-up significantly decreased compared with baseline. Among the 61 patients who had further follow-up echocardiographic examinations, 13% developed CTRCD. In the Cox-hazard model, worse Δbasal-LS was significantly associated with CTRCD. By Kaplan-Meier analysis, patients with Δbasal-LS decrease of more than the median value (-9.7%) had significantly worse event-free survival than those with a smaller decrease (p=0.015). Basal-LS significantly decreased prior to development of CTRCD, and worse basal-LS was associated with development of CTRCD in patients receiving anthracycline chemotherapy.


Bronchioalveolar stem cells derived from mouse-induced pluripotent stem cells promote airway epithelium regeneration

Bronchioalveolar stem cells (BASCs) located at the bronchioalveolar-duct junction (BADJ) are stem cells residing in alveoli and terminal bronchioles that can self-renew and differentiate into alveolar type (AT)-1 cells, AT-2 cells, club cells, and ciliated cells. Following terminal-bronchiole injury, BASCs increase in number and promote repair. However, whether BASCs can be differentiated from mouse-induced pluripotent stem cells (iPSCs) remains unreported, and the therapeutic potential of such cells is unclear. We therefore sought to differentiate BASCs from iPSCs and examine their potential for use in the treatment of epithelial injury in terminal bronchioles. BASCs were induced using a modified protocol for differentiating mouse iPSCs into AT-2 cells. Differentiated iPSCs were intratracheally transplanted into naphthalene-treated mice. The engraftment of BASCs into the BADJ and their subsequent ability to promote repair of injury to the airway epithelium were evaluated. Flow cytometric analysis revealed that BASCs represented ~ 7% of the cells obtained. Additionally, ultrastructural analysis of these iPSC-derived BASCs via transmission electron microscopy showed that the cells containing secretory granules harboured microvilli, as well as small and immature lamellar body-like structures. When the differentiated iPSCs were intratracheally transplanted in naphthalene-induced airway epithelium injury, transplanted BASCs were found to be engrafted in the BADJ epithelium and alveolar spaces for 14 days after transplantation and to maintain the BASC phenotype. Notably, repair of the terminal-bronchiole epithelium was markedly promoted after transplantation of the differentiated iPSCs. Mouse iPSCs could be differentiated in vitro into cells that display a similar phenotype to BASCs. Given that the differentiated iPSCs promoted epithelial repair in the mouse model of naphthalene-induced airway epithelium injury, this method may serve as a basis for the development of treatments for terminal-bronchiole/alveolar-region disorders.


A case of juvenile fibroadenoma arising from axillary accessory mammary gland

腋窩副乳発生と考えられる若年性線維腺腫の1例

A case is20years old woman. She had previously noticed a mass in the left axilla. The mass grew, so she went to the hospital. Ultrasonography revealed a 71 × 51 mm well-defined tumor in the left axilla. We suspected a benign tumor but could not rule out axillary lymph node metastasis or accessory breast cancer. The findings of fine needle aspiration cytology suggested fibroadenoma or phyllodes tumor. Although we diagnosed fibroadenoma by needle biopsy, a definitive diagnosis was made by tumor resection because it is located in the axilla and large in size, and other diseases such as phyllodes tumors can be distinguished. The histopathological diagnosis of the excised specimen was juvenile fibroadenoma. We report a case of juvenile fibroadenoma arising from the axillary accessory mammary gland.


Phase 1 Dose-Escalation Study of Triweekly Nab-Paclitaxel Combined With S-1 for HER2-Negative Metastatic Breast Cancer

To evaluate the efficacy, toxicity, maximum tolerated dose, and recommended dose of triweekly nab-paclitaxel (nab-PTX) and S-1 combination chemotherapy for patients with metastatic breast cancer. This phase 1 study was conducted with a standard 3 + 3 dose escalation design. Every 3 weeks, the patients received nab-PTX at 180-260 mg/m on day 1 and S-1 at 65-80 mg/m daily on days 1 to 14. Ten HER2-negative metastatic breast cancer patients were enrolled; their median number of prior chemotherapy regimens was 3. Dose-limiting toxicity was observed in the first patient assigned to level 4; grade 4 febrile neutropenia and grade 3 neurotoxicity such as needing a wheelchair occurred. Therefore, an additional patient was not assigned to level 4. The maximum tolerated dose was considered level 4 (260 mg/m nab-PTX with 80 mg/m S-1). The recommended dose determined was level 3 (220 mg/m nab-PTX with 80 mg/m S-1). The response rate was 60.0%. The disease control rate was 70.0%. This combination chemotherapy therapy was feasible and safe for patients with HER2-negative metastatic breast cancer.


Thoracoscopic lobectomy for lung cancer with unilateral absence of pulmonary artery


Tolerability and efficacy of a chemotherapy regimen avoiding Anthracycline for HER2 positive elderly and poor risked breast cancer patients

HER2陽性高齢者乳癌に対するAnthracycline系薬剤回避レジメンの忍容性と有効性についての検討

Tolerability and efficacy of chemotherapy avoiding anthracycline regimen were examined histologically in ER negative and HER2positive elderly and poor risked breast cancer patients because of serious toxicity of Anthracycline regimen. Neo-adjuvant chemotherapy with 4 to 6 courses of Paclitaxel with Trastuzumab was given to 6 patients, Pertuzumab was added in 2 cases to obtain complete response. Adverse events were controllable, the primary treatment was completed without reducing the dose of drugs(RDI was 100%). Clinical CR rate was recognized in all 6 patients and pathological CR was proved in all of the operated5cases.


Use of a prognostic risk score that aggregates the FDG-PET/CT SUVmax, tumor size, and histologic group for predicting the prognosis of pStage I lung adenocarcinoma

pStage I includes clinicopathologically diverse groups. This study aimed to identify the prognostic factors for pStage I lung adenocarcinoma. We retrospectively reviewed 208 patients with pStage I adenocarcinomas who underwent curative resection in our institute between 2006 and 2013. The maximum standardized uptake value (SUVmax) on [F18]-fluoro-deoxy-D-glucose positron emission tomography-computed tomography (PET/CT) was evaluated. Adenocarcinomas were categorized into the following histologic groups: group 0 (minimally invasive adenocarcinoma and lepidic predominant adenocarcinoma), group 1 (papillary predominant adenocarcinoma), and group 2 (acinar predominant adenocarcinoma and all the remaining subtypes). We assessed the relationship between disease-free survival (DFS) and clinicopathological factors. Multivariate analysis of DFS demonstrated that SUVmax > 3.0 (p < 0.001), total tumor size > 20 mm (p = 0.016), and histologic groups (p < 0.05) were independent prognostic factors. The prognostic risk score (PRS) was calculated using the following equation: PRS = SUVmax (≤ 3.0: 0 point, > 3.0: 2 points) + total tumor size (≤ 20 mm: 0 point, > 20 mm: 1 point) + histologic group (group 0: 0 point, group 1: 1 point, group 2: 2 points). Patients were divided into the following three risk groups: low-risk (PRS 0-2 points, n = 136), intermediate-risk (PRS 3-4 points, n = 49), and high-risk groups (PRS 5 points, n = 13). The 5-year DFS rates were 93.2%, 50.6%, and 30.8% for the low-, intermediate-, and high-risk groups, respectively (p < 0.001). The PRS aggregating the FDG-PET/CT SUVmax, total tumor size, and histologic group predicts the prognosis of pStage I lung adenocarcinoma.

International Journal of Clinical Oncology


DNA methylation of GHSR, GNG4, HOXD9 and SALL3 is a common epigenetic alteration in thymic carcinoma

Thymic epithelial tumors comprise thymoma, thymic carcinoma and neuroendocrine tumors of the thymus. Recent studies have revealed that the incidence of somatic non-synonymous mutations is significantly higher in thymic carcinoma than in thymoma. However, limited information is currently available on epigenetic alterations in these types of cancer. In this study, we thus performed genome-wide screening of aberrantly methylated CpG islands in thymoma and thymic carcinoma using Illumina HumanMethylation450 K BeadChip. We identified 92 CpG islands significantly hypermethylated in thymic carcinoma in relation to thymoma and selected G protein subunit gamma 4 (GNG4), growth hormone secretagogue receptor (GHSR), homeobox D9 (HOXD9) and spalt like transcription factor 3 (SALL3), which are related to cancer. We examined the promoter methylation of 4 genes in 46 thymic epithelial tumors and 20 paired thymus tissues using bisulfite pyrosequencing. Promoter methylation was significantly higher in thymic carcinoma than in thymoma and revealed a high discrimination between thymic carcinoma and thymoma in all 4 genes. Promoter methylation was higher in thymic carcinoma than in the thymus. No significant differences were observed in the promoter methylation of GNG4, HOXD9, or SALL3 between thymoma and the thymus. The promoter methylation of the 4 genes was not significantly higher in advanced-stage tumors than in early-stage tumors in all thymic epithelial tumors. Among the 4 genes, relapse-free survival was significantly worse in tumors with a higher DNA methylation than in those with a lower DNA methylation in all thymic epithelial tumors. Moreover, relapse-free survival was significantly worse in thymomas with a higher DNA methylation of HOXD9 and SALL3 than in those with a lower DNA methylation. On the whole, the findings of this study indicated that the promoter methylation of cancer-related genes was significantly higher in thymic carcinoma than in thymoma and the thymus. This is a common epigenetic alteration of high diagnostic value in thymic carcinoma and may be involved in the carcinogenesis of thymic carcinoma. However, epigenetic alterations in the 3 genes, apart from GHSR, are not involved in the tumorigenesis of thymoma.


Chromate exposure induces DNA hypermethylation of the mismatch repair gene MLH1 in lung cancer

Hexavalent chromium is recognized as a human carcinogen. Our previous studies revealed that lung cancer (LC) in chromate-exposed workers (chromate LC) had molecular features of frequent microsatellite instability (MSI), repression of MLH1 level, and aberrant DNA methylation of several tumor-suppressor genes, including MLH1. In the present study, we quantitatively investigated MLH1-promoter methylation status using bisulfite pyrosequencing of paired tumorous/nontumorous tissues from chromate and nonchromate LCs to determine the effect of chromate exposure on MLH1-promoter methylation. The methylation level of MLH1 promoter was significantly higher in chromate LC tumors (P < .001) than nonchromate LC tumors and, among chromate LC, significantly higher in tumorous tissue than nontumorous tissue (P = .004). Moreover, the methylation level of MLH1 promoter in normal lung tissue tended to be higher in chromate LC than nonchromate LC (P = .062). In addition, LC with reduced levels of MLH1 showed significantly higher methylation levels of MLH1 promoter than LC exhibiting normal MLH1 levels (P = .019). Moreover, immunohistochemical analyses determined that levels of SUV39H1, an H3K9me2-related methyltransferase, were higher in chromate LC than nonchromate LC (P = .076). Furthermore, we evaluated three DNA double-strand break-repair genes (MRE11, RAD50, and DNA-PKcs) as possible targets of MSI by fragment-length polymorphism analysis, revealing the mutation frequency of RAD50 as significantly higher in chromate LC than nonchromate LC (P = .047). These results suggest that chromate exposure might induce MLH1 hypermethylation in LC as a mechanism of chromate-induced carcinogenesis.


Transbronchial Biopsy Using an Ultrathin Bronchoscope Guided by Cone-Beam Computed Tomography and Virtual Bronchoscopic Navigation in the Diagnosis of Pulmonary Nodules

Transbronchial biopsy is a safe diagnostic approach for patients with peripheral pulmonary lesions; however, the diagnostic yield is low. This study was conducted to evaluate the feasibility and diagnostic yield of transbronchial biopsy using the combination of an ultrathin bronchoscope, virtual bronchoscopic navigation (VBN), and cone-beam computed tomography (CBCT). Patients with peripheral pulmonary lesions, no >30 mm, with the responsible bronchus, were prospectively included. An ultrathin bronchoscope and biopsy forceps were advanced to the target bronchus under VBN, 2D-fluoroscopy, and CBCT. We categorized the CBCT findings before biopsy into 3 types according to positions of the target lesion and forceps (CBCT target-forceps sign). In type A, the forceps reached the inside of the target lesion. In type C, the forceps could not reach the lesion. When the CBCT findings could not be categorized into either type A or C, the sign was categorized as type B. Although the target lesions were invisible by conventional C-arm fluoroscopy in 29 patients, CBCT visualized all 40 lesions. The overall diagnostic yield was 90.0%, and diagnostic yields for malignant and benign lesions were 92.0 and 86.7%, respectively. Diagnostic yields for CBCT target-forceps sign types A, B, and C were 100, 75.0, and 0%, respectively. Four undiagnosed patients proceeded to other diagnostic procedures based on the CBCT target-forceps sign (type B: n = 2, type C: n = 2) and were correctly diagnosed without delay. Transbronchial biopsy using an ultrathin bronchoscope guided by CBCT and VBN showed a very high yield in the diagnosis of pulmonary nodules.


Regional cooperation for cancer patients : A questionnaire clarifying the roles of community doctor

がんの地域連携 かかりつけ医との役割分担に関するアンケート調査

It was suggested long ago that regional cooperation is necessary for cancer patients. Both doctors in base hospitals and community doctors understand the importance of such cooperation. Here we report the results of our widely distributed questionnaire designed to clarify the division of physicians' roles and to strengthen the relationships between base hospital and community doctors. The questionnaire asks whether community doctors can accept cancer patients and what types of medical treatment the doctors can provide for patients with esophageal cancer, lung cancer, breast cancer, and thyroid cancer. The doctors in 289 of 550 (53%) facilities completed and returned the questionnaire. About half of the community doctors responded that they can accept patients with any of the four cancers and can provide most types of the necessary medical examinations and treatments in their daily practices. Most of the community doctors indicated that they could not provide some anti-cancer drugs and supportive drug therapies for breast cancer patients. The development and implementation of a clinical pathway system could enable the participation of more community doctors and base hospital doctors. Although our findings are preliminary, they will contribute to a foundation for building better regional corporative relationships with community doctors who treat cancer patients.


Indocyanine green fluorescence imaging for resection of pulmonary metastasis of hepatocellular carcinoma

Indocyanine green (ICG) accumulates in hepatocellular carcinoma (HCC), and tumor fluorescence can be observed under irradiation with near infrared light (NIR). This study investigated the clinical utility of ICG fluorescence imaging during resection of pulmonary metastases of HCC. From April 2010 to June 2018, six patients with suspected pulmonary metastasis of HCC were enrolled prospectively. Prior to surgery, all patients underwent the ICG hepatic function test following intravenous administration of ICG (0.5 mg/kg body weight). During surgery, metastatic HCC was identified by observation of ICG fluorescence, allowing assessment of the surgical margin. Tumor fluorescence was also evaluated on cut sections. A total of 11 metastatic HCCs were resected in six patients at nine operations. Eight lesions were removed by wedge resection and 3 lesions were managed by lobectomy. During surgery, tumor fluorescence could be confirmed through the visceral pleura in 6 out of 7 lesions treated by wedge resection, while NIR irradiation was difficult for 1 lesion. For these 6 lesions, the median distance from the tumor to the visceral pleura and the median surgical margin were 0 mm (range, 0-2 mm) and 14 mm (range, 11-17 mm), respectively. When cut sections were examined, all tumors emitted fluorescence. All lesions were histologically confirmed to be metastatic HCC. In patients with pulmonary metastasis of HCC, ICG fluorescence imaging is useful for identifying the tumor and securing its margin when the lesion is peripheral and wedge resection is planned.


Evaluation of the components of mediastinal cystic lesions using imaging techniques

To identify and differentiate patients with mediastinal cysts from those with cystic tumors requiring surgery. A total of 36 patients with mediastinal cystic lesions were enrolled. The patients were separated into two groups based on pathological findings : those with mediastinal cysts (n=23) and those with mediastinal tumors (n=13). The cystic components were measured using imaging parameters including mean computed tomography (CT) value, apparent diffusion coefficient (ADC), T1 signal intensity ratio (T1SIratio), and T2 signal intensity ratio (T2SI-ratio), acquired from magnetic resonance imaging (MRI) ; and standardized maximum uptake value (SUVmax) fromF-fluorodeoxyglucose positron emission tomography/computed tomography (F-FDG PET/CT). Both groups were statistically compared. Comparative parameters between the cysts and tumors revealed the following ratios : CT value, 40.9?21.2 versus (vs) 24.8?12.9 (p = 0.019) ;SUVmax, 1.18?0.50 vs 4.32?3.52 (p = 0.003) ; ADC, 3.46?0.96 vs 2.68?0.74 (p = 0.022) ; T1SI-ratio, 1.06?0.60 vs 1.35? 0.92 (p = 0.648) ; T2SI-ratio, 5.40?1.80 vs 4.33?1.58 (p = 0.194). However, there was no correlation between FDG uptake and ADC value. SUVmax fromF-FDG PET/CT and ADC derived from MRI were effective in facilitating preoperative diagnosis to differentiate mediastinal cysts from tumors. However, these examinations may be complementary to one another, not dominant. J. Med. Invest. 66 : 106-111, February, 2019.

The Journal of Medical Investigation : JMI


Phase II Study of S-1 Combined With Low-Dose Docetaxel as Neoadjuvant Chemotherapy for Operable Breast Cancer Patients (N-1 Study)

To improve the pathological complete response (pCR) rate, we devised new neoadjuvant chemotherapy. Efficacy and safety of the oral fluoropyrimidine derivative S-1 (Taiho Pharmaceutical Co, Tokyo, Japan) combined with low-dose docetaxel (S-1+DOC) were evaluated. Patients were treated with docetaxel (40 mg/m intravenously on day 1) and S-1 (40 mg/m orally twice per day on days 1-14) every 3 weeks for 4 cycles. In accord with the Response Evaluation Criteria In Solid Tumors version 1.1 criteria, the patients who showed a complete response (CR) underwent surgery, and those who achieved a partial response (PR) underwent 4 more cycles of S-1+DOC. Patients who achieved stable disease (SD) or progressive disease (PD) received EC (epirubicin and cyclophosphamide) or HT (trastuzumab and paclitaxel) according to their HER2 status. The primary end point was the pCR rate. Ninety-four patients entered the study. After 4 cycles of S-1+DOC, CR was noted in 5 patients, PR in 57, SD in 18, and PD in 3. Of the patients who achieved SD and PD, 12 received EC, and 9 received HT. Among the 83 assessable patients, the pCR rate was 34.9%, and the response rate was 80.7%. The pCR rates were 19.5% in the luminal type group, 53.8% in the luminal HER2 group, 46.1% in the HER2 group, and 50.0% in the triple-negative group. The S-1+DOC regimen in this study could be well tolerated and a new candidate neoadjuvant chemotherapy in operable breast cancer patients. It is also expected to be effective even in patients with luminal type disease. However, further randomized control trials are needed to ascertain whether pCR can contribute to favorable outcomes.


A case of thoracoscopic medial basal segmentectomy

Isolated resection of the medial basal segment (S7) is uncommon because of its small volume, and S7 segmentectomy is considered to be difficult due to anatomical variation. We report a case of successful thoracoscopic S7 segmentectomy. A 56-year-old man was referred to our hospital with suspected pulmonary metastasis of rectal cancer. A 6-mm nodule was detected in S7. A7 and B7 branched from the basal segmental artery and bronchus, respectively, to run ventral to the inferior pulmonary vein. This made it possible to isolate A7 and B7 by an approach via the interlobar fissure. In addition, V7a and V7b were easily isolated from inferior pulmonary vein. The intersegmental plane was indicated by V7b and was transected along a demarcation line identified by using selective oxygenation via B7. B7 most commonly branches from the basal bronchus and A7 from the basal artery to run ventral to the inferior pulmonary vein. With this anatomical type, when the surgeon approaches via the interlobar fissure during surgery, A7 is identified first, B7 is seen behind A7, and the IPV is posterior to B7. Since the intersegmental plane is located ventral to the IPV, segmentectomy can be completed via the interlobar fissure approach. In patients with this pattern of pulmonary artery and bronchial anatomy, isolated S7 segmentectomy is a feasible treatment option.

International Journal of Surgery Case Reports


CT lymphography for superficial esophageal cancer. Lymph Node Metastasis in Gastrointestinal Cancer" Part IV. Sentinel node navigation surgery, Chapter 17, Methodology: CT lumphography

Lymph Node Metastasis in Gastrointestinal Cancer. Ed. By Natsugoe S, Springer-Verlag, Tokyo


Case reports : A case of advanced breast cancer with spinal palsy due to cervical bone metastasis who was improved a quality of life by emergent multidisciplinary oncological salvage

乳癌頚椎転移による脊髄麻痺に対して迅速な集学的治療によりQOLの改善が得られた1例

A 60s female complained of right thigh pain caused by bone metastasis from advanced breast cancer. She was introduced to our ward for systemic therapy with palliative radiation to painful osteolytic lesion in the right femur. She suddenly complained of serious pain and motility disturbance in the right upper-extremity two days after her admission. Magnetic resonance imaging(MRI)suggested bone metastasis in the 3rd cervical vertebra which compressed spinal cord. We discussed about an optimal treatment with the orthopedic surgeon and the radiation therapeutic physician, and laminectomy was scheduled promptly. She also had a right femur fracture a day before her planed laminectomy, so she underwent osteosynthesis of the femur together with laminectomy of the cervical vertebra. She also received the irradiation to the 3rd cervical vertebra and the shaft of right femur. She became able to eat with a spoon by herself and her activity of daily living(ADL)have fully recovered by daily rehabilitation. She is receiving chemotherapy in our out-patient clinic now. We recognized that an emergent oncological treatment for the spinal decompression by the bone metastasis could improve the patients' quality of life(QOL)to avoid the permanent paralysis and also their prognoses.


Selective lobar blockade for lung resection : A report of two cases

選択的肺葉ブロックを用いた肺切除の2例

There are cases in which one-lung ventilation is difficult due to contralateral lung resection or low lung function. Selective lobar blockade can improve oxygenation compared with one-lung ventilation and secure a good operative field by inducing partial collapse. We report two cases of lung resection involving selective lobar blockade. (Case1) An 80-year-old female had previously undergone right upper and middle lobectomy for multiple lung tumors. Surgery was scheduled to remove a 7‐mm ground glass opacity from the upper left lobe. Oral intubation was performed (inner diameter of intubation tube:8mm). Next, the left upper lobe bronchus was blocked with a7Fr Arndt blocker under bronchoscopy, and partial resection of the left upper lobe was conducted. (Case2) A 75-year-old male had previously undergone right upper lobectomy for pulmonary tuberculosis and had developed right chronic empyema. Surgery was scheduled to remove a 22-mm nodule from the left lingular segment. Oral intubation was performed(inner diameter of intubation tube:8．5mm). Next, the left lingual bronchus was blocked with a7Fr Arndt blocker under bronchoscopy. Left lingular segmentectomy was carried out under thoracoscopic assistance. Intraoperative oxygenation was maintained in both cases, and the release of the block due to hypoxemia was not required in either case.


The effects of the herbal medicine Daikenchuto (TJ-100) after esophageal cancer resection, open-label, randomized controlled trial

Daikenchuto (TJ-100), a traditional Japanese herbal medicine, is widely used in Japan. Its effects on gastrointestinal motility and microcirculation and its anti-inflammatory effect are known. The purpose of this prospective randomized controlled trial was to investigate the effect of TJ-100 after esophagectomy in esophageal cancer patients. Forty patients for whom subtotal esophageal resection for esophageal cancer was planned at our institute from March 2011 to August 2013 were enrolled and divided into two groups at the point of determination of the operation schedule after informed consent was obtained: a TJ-100 (15 g/day)-treated group (n = 20) and a control group (n = 20). The primary efficacy end-points were maintenance of the nutrition condition and the recovery of gastrointestinal function. The secondary efficacy end-points were the serum C-reactive protein (CRP) level and adrenomedullin level during the postoperative course, the incidence of postoperative complications, and the length of hospital stay after surgery. We examined 39 patients because one patient in the TJ-100 group was judged as having unresectable cancer after surgery. The mean age of the TJ-100 group patients was significantly older than that of the control group patients.The rate of body weight decrease at postoperative day 21 was significantly suppressed in the TJ-100 group (3.6% vs. the control group: 7.0%, p = 0.014), but the serum albumin level was not significantly different between the groups. The recovery of gastrointestinal function regarding flatus, defecation, and oral intake showed no significant between-group differences, but postoperative bowel symptoms tended to be rare in the TJ-100 group. There was no significant between-group difference in the length of hospital stay after surgery. The serum CRP level at postoperative day 3 was 4.9 mg/dl in the TJ-100 group and 6.9 mg/dl in the control group, showing a tendency of a suppressed serum CRP level in the TJ-100 group (p = 0.126). The rate of increase in adrenomedullin tended to be high postoperatively, but there was no significant difference between the two groups. TJ-100 treatment after esophageal cancer resection has the effects of prompting the recovery of gastrointestinal motility and minimizing body weight loss, and it might suppress the excess inflammatory reaction related to surgery.


A feasibility study of postoperative adjuvant chemotherapy with fluoropyrimidine S-1 in patients with stage II-IIIA non-small cell lung cancer.

Adjuvant chemotherapy with uracil tegafur (UFT) improved survival among patients with completely resected stage I lung adenocarcinoma. S-1, an oral dihydropyrimidine dehydrogenase (DPD)-inhibitory 5-fluorouracil, is a more potent DPD inhibitor than UFT;therefore, we hypothesized that postoperative adjuvant chemotherapy with S-1 would be effective for advanced non-small cell lung cancer (NSCLC). We conducted a feasibility study of S-1 as postoperative adjuvant chemotherapy in patients with curatively resected pathological stage bold I back 10 bold I and bold I back 10 bold I back 20 bold I A NSCLC. Adjuvant chemotherapy consisted of 9 courses (4-week administration, 2-week withdrawal) of S-1 at 80-120 mg/body per day. Twenty-four patients with completely resected NSCLC were enrolled in this study from November 2007 through December 2010. The primary endpoint was the rate of completion of the scheduled adjuvant chemotherapy. The secondary endpoints were safety, overall survival, and relapse-free survival. Five patients were censored because of disease recurrence. The planned 9 courses of S-1 were administered to completion in 8 patients. Twelve patients completed more than 70% of the planned courses. Grade 3 adverse reactions, such as elevated total bilirubin (4.2%) and pneumonitis (4.2%), were observed, but there were no Grade 4 adverse reactions. Patients who completed more than 70% of the 9 courses demonstrated better overall survival than those who completed less than 70%. Postoperative administration of S-1 may be possible with few severe adverse events as adjuvant chemotherapy for patients with curatively resected pathological stage bold I back 10 bold I -bold I back 10 bold I back 20 bold I A NSCLC. J. Med. Invest. 65:90-95, February, 2018.


多職種連携による緩和治療が有効であった乳腺悪性葉状腫瘍の1例

多職種連携による緩和治療が有効であった乳腺悪性葉状腫瘍の1例

The case subject was a woman in her50s who consulted her local clinic for the chief complaint of pain extending from the left buttock to the lower leg. A sacral lesion and giant mass in the right breast were observed, and thus on suspicion of breast cancer the subject was referred to our department. The results of needle biopsy led to the definite diagnosis of malignant phyllodes tumor. At the start of treatment the subject presented markedly reduced activities of daily living due to the pain, and upon the introduction of opioids, and performing palliative irradiation for the sacral metastasis, the pain was successfully alleviated relatively quickly. During this period, the primary lesion became ulcerated and progression of anemia was also observed, and therefore upon applying metronidazole ointment and commencing irradiation for the right breast, therapeutic effects such as tumor regression and control of anemia progression were observed. After the initial consultation the subject expressed severe anxiety, and thus intervention was requested from a nurse specialist in cancer care, who sat with the patient when her condition was explained, and listened closely to her anxiety. Thereafter, 2 courses of epirubicin and cyclophosphamide therapy as systemic chemotherapy were administered, however the disease progressed. The subject desired to receive care at a local medical institution, and thus it was decided with the help of a social worker that she be transferred to a hospice in the short-term.


A case of atypical type A thymoma with vascular invasion and lung metastasis

We present a case of type A thymoma with invasion of the left brachiocephalic vein and lung metastases. An 84-year-old man underwent extended thymectomy combined with left brachiocephalic vein reconstruction and resection of a lung metastasis. Histological examination showed vascular invasion by the tumor. The lung metastasis had high mitotic activity and slight nuclear enlargement, the so-called "atypical" features, but the main part of the primary tumor did not. However, the intravascular portion of the tumor had "atypical" histological features like the lung metastasis. It seems that "atypical" histological features are related to clinically malignant behavior.

General Thoracic and Cardiovascular Surgery


Frequent silencing of RASSF1A by DNA methylation in thymic neuroendocrine tumours

Aberrant methylation of promoter CpG islands (CGIs) of tumour suppressor genes is a common epigenetic mechanism underlying cancer pathogenesis. The methylation patterns of thymic tumours have not been studied in detail since such tumours are rare. Herein, we sought to identify genes that could serve as epigenetic targets for thymic neuroendocrine tumour (NET) therapy. Genome-wide screening for aberrantly methylated CGIs was performed in three NET samples, seven thymic carcinoma (TC) samples, and eight type-B3 thymoma samples. The methylation status of thymic epithelial tumours (TETs) samples was validated by pyrosequencing in a larger cohort. The expression status was analysed by quantitative polymerase chain reaction (PCR) and immunohistochemistry. We identified a CGI on a novel gene, RASSF1A, which was strongly hypermethylated in NET, but not in thymic carcinoma or B3 thymoma. RASSF1A was identified as a candidate gene statistically and bibliographically, as it showed frequent CGI hypermethylation in NET by genome-wide screening. Pyrosequencing confirmed significant hypermethylation of a RASSF1A CGI in NET. Low-grade NET tissue was more strongly methylated than high-grade NET. Quantitative PCR and immunohistochemical staining revealed that RASSF1A mRNA and protein expression levels were negatively regulated by DNA methylation. RASSF1A is a tumour suppressor gene epigenetically dysregulated in NET. Aberrant methylation of RASSF1A has been reported in various tumours, but this is the first report of RASSF1A hypermethylation in TETs. RASSF1A may represent an epigenetic therapeutic target in thymic NET.


Malignant Pleural Mesothelioma Presenting Refractory Pneumothorax Successfully Treated by Intrapleural Administration of Diluted Fibrin Glue : Report of a Case

悪性胸膜中皮腫に合併した難治性気胸に対し胸腔内フィブリン糊注入療法が有効であった1例

The Japanese Journal of Thoracic Surgery


Autofluorescence for the diagnosis of visceral pleural invasion in non-small-cell lung cancer

This study was conducted to evaluate the accuracy of autofluorescence as a mode of diagnosis for visceral pleural invasion of non-small-cell lung cancer compared with white-light by means of clinical questions to several thoracic surgeons. Eight independent thoracic surgeons evaluated visceral pleural invasion in 25 cases of non-small-cell lung cancer attached to the visceral pleura on lung windows of preoperative computed tomography images. At the first study meeting to evaluate the accuracy of visceral pleural invasion diagnosis using conventional white-light images, the surgeons diagnosed visceral pleural invasion based on information in preoperative computed tomography images, histological types and videos recorded with white-light mode using a thoracoscope. At the second study meeting to evaluate the accuracy of visceral pleural invasion diagnosis using autofluorescence, the same surgeons diagnosed visceral pleural invasion based on information in 2 videos recorded in white-light mode and in autofluorescence mode using the thoracoscope. The overall average sensitivity, specificity and accuracy of visceral pleural invasion diagnosis by white-light versus autofluorescence mode were 64.6% vs 83.3%, 53.9% vs 73.7% and 56.5% vs 76.0%, respectively. The sensitivity, specificity and accuracy of visceral pleural invasion diagnosis was improved through the additional use of the autofluorescence mode compared with the white-light mode alone.

European Journal of Cardio-Thoracic Surgery


Gender differences in clinicopathological features and prognosis of squamous cell carcinoma of the esophagus


肺癌手術における周術期口腔機能管理の術後肺炎予防効果

肺癌手術における周術期口腔機能管理の術後肺炎予防効果

The Journal of the Japanese Association for Chest Surgery


Surgical resection after BEP therapy induced interstitial pneumonia during treatment for primary mediastinal malignant germ cell tumor

縦隔原発悪性胚細胞性腫瘍に対するBEP療法中に発症した間質性肺炎治療後に手術を施行した2例

The incidence of interstitial pneumonia caused by bleomycin is increasing, dependent on the total dose. Care should be taken in the treatment of a germ cell tumor requiring high-dose administration. If interstitial pneumonia occurs during treatment for a primary mediastinal malignant germ cell tumor, it may influence the subsequent surgical treatment. We report two surgical cases of interstitial pneumonia that occurred during BEP (bleomycin+etoposide+cisplatin) therapy for a primary mediastinal malignant germ cell tumor. Case 1 was a 19-year-old man and case 2 was a 24-year-old man. They both had an anterior mediastinal tumor of around 10 cm in diameter that was diagnosed as a yolk sac tumor by needle biopsy, and received BEP therapy. Interstitial pneumonia occurred at total bleomycin doses of 360 and 330 mg, respectively. They received steroid pulse treatment 103 and 109 days after starting therapy, respectively. Thereafter, they received steroid maintenance treatment by oral administration. Because they showed the improvement of interstitial pneumonia on imaging examinations, they received residual tumor resection and partial resection of the lung 17 and 26 days after starting steroid pulse treatment, respectively. Both post-operative courses were good, without the onset of respiratory failure.

ブレオマイシンによる間質性肺炎は総投与量依存性に頻度が増加する．高容量投与が必要となる縦隔胚細胞性腫瘍において，治療中に間質性肺炎を生じた場合は，その後の手術にも影響がおよぶ可能性がある．今回BEP(bleomycin+etoposide+cisplatin)療法中に生じた間質性肺炎を治療し，早期に手術を施行した2例を報告する．症例1は19歳の男性，症例2は24歳男性で，ともに前縦隔に約10 cmの腫瘍を認め，針生検で卵黄囊腫瘍と診断された．BEP療法を開始し，それぞれ，ブレオマイシン総投与量360，330 mgで間質性肺炎を発症した．化学療法開始103日目，109日目から3日間のステロイドパルスを行い，その後内服で維持療法を行った．画像上，間質性肺炎の改善を認めたため，手術はパルス療法開始後17日目と26日目に残存腫瘍切除と肺部分切除を行った．ともに術後呼吸不全の発症なく経過良好であった．


A case of subcutaneous emphysema induced by a portable thoracic drainage system after pneumonectomy

A 62-year-old man was admitted to our hospital for squamous cell lung carcinoma. We performed video-assisted right pneumonectomy after the induction chemoradiation therapy. We used portable thoracic drainage systems: Thopaz® and 19-Fr blake drain®. The patient had a severe cough and showed progressive subcutaneous emphysema. Thopaz® showed little air leakage. We confirmed the absence of a fistula at the bronchial stump via bronchoscopy and the absence of air suction from outside the drainage tube. We removed the thoracic drain because we believed Thopaz® caused the subcutaneous emphysema, and the subcutaneous emphysema subsequently fully resolved.

Thopaz® regulates the mean intrathoracic pressure by supplying air to the thoracic cavity when there is an excessive negative intrathoracic pressure. The mechanism of the increased subcutaneous emphysema by Thopaz® was considered as follows: sudden elevation of the intrathoracic pressure caused by the cough moved intrathoracic air into the subcutaneous space, instead of the blake drain®. Thopaz® supplied air into the thoracic cavity to restore the excessive negative intrathoracic pressure. This cycle was repeated and the subcutaneous emphysema worsened.

症例は62歳男性．右肺扁平上皮癌にて術前放射線化学療法後に胸腔鏡補助下右肺全摘術(ND2a-2)を施行した．ポータブル型胸腔ドレナージ装置であるThopazⓇ(トパーズ)にblakeドレーンⓇをつなげて術後胸腔内ドレナージした．術後，咳嗽が多く認められ，皮下気腫が増加した．トパーズのエアリーク表示量はほぼ0 ml/分であった．気管支鏡で気管支断端瘻がないことを確認した．トパーズのドレナージトラブルと判断し，ドレーン抜去すると皮下気腫は軽快した．トパーズには胸腔内圧調節機能があり，胸腔内が過陰圧になるとバルブが開き空気を吸い込ませる機能がある．本症例では咳嗽による急激な胸腔内圧上昇時に胸腔内の空気が皮下に漏れ，その結果起こった胸腔内圧の低下を感知したトパーズ経由で胸腔内へ空気が流入するという機序を繰り返したと考えられた．

The Journal of the Japanese Association for Chest Surgery