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Colorectal cancer (CRC) is well characterized in terms of genetic mutations and the mechanisms by which they contribute to carcinogenesis. Mutations in APC, TP53, and KRAS are common in CRC, indicating key roles for these genes in tumor development and progression. However, for certain tumors with low frequencies of these mutations that are defined by tumor location and molecular phenotypes, a carcinogenic mechanism dependent on BRAF mutations has been proposed. We here analyzed targeted sequence data linked to clinical information for CRC, focusing on tumors with a high tumor mutation burden (TMB) in order to identify the characteristics of associated mutations, their relations to clinical features, and the mechanisms of carcinogenesis in tumors lacking the major driver oncogenes. Analysis of overall mutation frequencies confirmed that APC, TP53, and KRAS mutations were the most prevalent in our cohort. Compared with other tumors, TMB-high tumors were more frequent on the right side of the colon, had lower KRAS and higher BRAF mutation frequencies as well as a higher microsatellite instability (MSI) score, and showed a greater contribution of a mutational signature associated with MSI. Ranking of variant allele frequencies to identify genes that play a role early in carcinogenesis suggested that mutations in genes related to the DNA damage response (such as ATM and POLE) and to MSI (such as MSH2 and MSH6) may precede BRAF mutations associated with activation of the serrated pathway in TMB-high tumors. Our results thus indicate that TMB-high tumors suggest that mutations of genes related to mismatch repair and the DNA damage response may contribute to activation of the serrated pathway in CRC., (© 2025 The Author(s). Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.) more...

Background: In the field of abdominal surgery, including colorectal cancer surgery, robotic surgery has become widespread, and the introduction of new robotic platforms is increasing. As a result, the incidence of subcutaneous emphysema (SE) as a postoperative complication has increased; however, the causes, grade, and perioperative course of SE have not been definitively examined. Therefore, we aimed to evaluate potential risk factors of SE after robotic colorectal cancer surgery., Methods: Between November 2022 and March 2024, 244 consecutive patients who underwent robotic colorectal cancer surgery using the da Vinci Xi (n = 190) or the hinotori™ platform (n = 54) were retrospectively analyzed. Risk factors associated with postoperative SE were assessed by multivariate analysis using logistic regression models. Moreover, the grade of SE and its perioperative course were investigated based on the two robotic platforms., Results: Postoperative SE was observed in 95 patients (38.9%). Nine patients (3.7%) had severe SE. The risk factors for SE were female sex, older age (≥ 80 years), and maximum intraabdominal pressure (max IAP) with CO 2 insufflation > 10 mmHg (odds ratio [95% confidence interval]: 1.981 [1.105-3.552], p = 0.022; 2.765 [1.310-5.835], p = 0.008; and 13.249 [1.227-143.020], p = 0.033, respectively). Additionally, the incidence of SE when using the hinotori™ platform was significantly lower than when using the da Vinci Xi platform (0.302 [0.135-0.667], p = 0.004)., Conclusions: Max IAP with CO 2  > 10 mmHg was associated with SE during robotic colorectal cancer surgery. Compared with the use of da Vinci Xi, the use of hinotori™ was associated with fewer incidences of postoperative SE, especially in females and older patients (≥ 80 years)., Competing Interests: Declarations. Disclosures: Tsutomu Kumamoto, Koki Otsuka, Junichiro Hiro, Hiroko Taniguchi, Yeongcheol Cheong, Yusuke Omura, Gaku Inaguma, Yosuke Kobayashi, Megumu Kamisima, Kazuki Tsujimura, Yuko Chikaishi, Koji Masumori, Ichiro Uyama, and Koichi Suda declare that they have no conflict of interest in connection with the submitted article. Ichiro Uyama has received lecture fees from Intuitive Surgical, Inc., and Medtronic, Inc., outside of the submitted work. Ichiro Uyama has been funded by Medicaroid, Inc., in relation to the Collaborative Laboratory for Research and Development in Advanced Surgical Technology, Fujita Health University. Koichi Suda has been funded by Sysmex, Co., in relation to the Collaborative Laboratory for Research and Development in Advanced Surgical Intelligence, Fujita Health University, outside of the submitted work. K.S. received research expenses from Sysmex, Co. and Medtronic Japan Co., Ltd., unrelated to the present study., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.) more...

Background: The da Vinci™ Surgical System, recognized as the leading surgical robotic platform globally, now faces competition from a growing number of new robotic surgical systems. With the expiration of key patents, innovative entrants have emerged, each offering unique features to address limitations and challenges in minimally invasive surgery. The hinotori™ Surgical Robot System (hinotori), developed in Japan and approved for clinical use in November 2022, represents one such entrant. This study demonstrates initial insights into the application of the hinotori in robot-assisted surgeries for patients with rectal neoplasms., Methods: The present study, conducted at a single institution, retrospectively reviewed 28 patients with rectal neoplasms treated with the hinotori from November 2022 to March 2024. The surgical technique involved placing five ports, including one for an assistant, and performing either total or tumor-specific mesorectal excision using the double bipolar method (DBM). The DBM uses two bipolar instruments depending on the situation, typically Maryland bipolar forceps on the right and Fenestrated bipolar forceps on the left, to allow precise dissection, hemostasis, and lymph node dissection., Results: The study group comprised 28 patients, half of whom were male. The median age was 62 years and the body mass index stood at 22.1 kg/m 2 . Distribution of clinical stages included eight at stage I, five at stage II, twelve at stage III, and three at stage IV. The majority, 26 patients (92.9%), underwent anterior resection using a double stapling technique. There were no intraoperative complications or conversions to other surgical approaches. The median operative time and cockpit time were 257 and 148 min, respectively. Blood loss was 15 mL. Postoperative complications were infrequent, with only one patient experiencing transient ileus. A median of 18 lymph nodes was retrieved, and no positive surgical margins were identified., Conclusions: The introduction of the hinotori for rectal neoplasms appears to be safe and feasible, particularly when performed by experienced robotic surgeons. The double bipolar method enabled precise dissection and hemostasis, contributing to minimal blood loss and effective lymph node dissection., (© 2024. The Author(s).) more...

Background: Adenosquamous carcinoma of the pancreas (ASCP) accounts for only 1-4% of all pancreatic exocrine cancers and has a particularly poor prognosis. The efficacy of chemotherapy for ASCP remains unknown because of the small number of cases, and few studies have evaluated conversion-intended chemotherapy., Case Presentation: A 76-year-old woman was referred to our hospital because of epigastric pain and nausea. A preoperative contrast-enhanced multidetector row computed tomography (MDCT) scan revealed a 17 × 17 mm low-density tumor with an ill-defined margin at the arterial phase in the pancreatic head. The tumor involved the common hepatic artery, left hepatic artery bifurcated from the common hepatic artery, and gastroduodenal artery, and was in contact with the portal vein. Fluorodeoxyglucose-positron emission tomography (FDG-PET) showed an uptake in the pancreatic head but no evidence of distant metastasis. The tumor was diagnosed as an adenocarcinoma of the pancreatic head and staged unresectable because the common and left hepatic arteries were involved. Hence, the patient underwent seven courses of conversion-intended chemotherapy using gemcitabine and nab-paclitaxel for pancreatic ductal adenocarcinoma over 7 months. After chemotherapy, the tumor shrank to 10 × 10 mm on contrast-enhanced MDCT. Consequently, the boundary between the tumor and major vessels of the common and left hepatic arteries and the portal vein became clear, and the involvement of the arteries with the tumor was evaluated to be released. The contact of the tumor to the portal vein also reduced to less than half the circumference of the portal vein. FDG-PET showed decreased accumulation in the tumor. Hence, the tumor was judged resectable, and pancreaticoduodenectomy was performed. The tumor and major blood vessels were easily dissected and R0 resection was achieved. The patient experienced no major complications and was discharged on postoperative day 28. The tumor was revealed as ASCP via pathological examination. The patient is alive and recurrence-free seven months after surgery. This is the first report of successful R0 resection for an initially unresectable ASCP following conversion-intended chemotherapy using gemcitabine and nab-paclitaxel regimen., Conclusions: Conversion-intended chemotherapy using gemcitabine and nab-paclitaxel regimen may be effective for ASCP., (© 2024. The Author(s).) more...

Background: Hydrocele of the canal of Nuck (HCN) is a rare disease, and its indications for laparoscopic surgery are not well-established., Case Presentation: A 53-year-old woman was referred to our hospital due to an uncomfortable thumb-sized inguinal mass. Preoperative computed tomography scan and magnetic resonance imaging revealed a hydrocele extending from the abdominal cavity around the left deep inguinal ring via the inguinal canal to the subcutaneous space. The patient was diagnosed with HCN protruding into the abdominal cavity and extending to the subcutaneous space. Laparoscopy can easily access the hydrocele protruding into the abdominal cavity. Furthermore, laparoscopic hernioplasty can be superior to the anterior approach for females. Hence, laparoscopic surgery was performed. After transecting the round ligament of the uterus, a tense 3-cm hydrocele was dissected with it. In order to approach the hydrocele distal to the deep inguinal ring, the transversalis fascia was incised medially to the inferior epigastric vessels. The subcutaneously connected hydrocele was excised from the incision. Then, the enlarged deep inguinal ring was reinforced using a mesh with the laparoscopic transabdominal preperitoneal approach. The patient was discharged 2 days postoperatively. Laparoscopic resection can be more effective for a hydrocele protruding into the abdominal cavity as it facilitates an easy access to the hydrocele. Moreover, laparoscopic resection of a hydrocele extending from the inguinal canal to the subcutaneous space via a transversalis fascia incision can be safer, with low risk of injury to the inferior epigastric vessels. The incised transversalis fascia and the enlarged deep inguinal ring due to the HCN were simultaneously repaired with the laparoscopic transabdominal preperitoneal repair. There are two reports on laparoscopic resection via a transversalis fascia incision for HCNs located between the inguinal canal and the subcutaneous space, which does not require intraperitoneal hydrocelectomy. However, this is the first report on laparoscopic resection of large HCNs protruding into the abdominal cavity and extending beyond the inguinal canal into the subcutaneous space via intraperitoneal hydrocelectomy and a transversalis fascia incision., Conclusions: Laparoscopic surgery with transversalis fascia incision can be useful for HCNs extending from the abdominal cavity to the subcutaneous space., (© 2024. The Author(s).) more...

A 78-year-old male who was undergoing treatment for diabetes was referred to our department after a chest X-ray revealed an abnormal shadow in the left upper lung field. A chest contrast-enhanced CT showed a tumor in the left upper lobe and a cystic lesion in the left lower lobe. Two aberrant arteries branching from the aorta were identified near the cyst. The patient was diagnosed with lung cancer and anomalous systemic arterial supply to the basal segment of the left lung (ABLL), necessitating surgical intervention. Thoracoscopic surgery was performed, with the left upper segmentectomy guided by Indocyanine green (ICG) to facilitate precise intersegmental plane identification. The two aberrant arteries were resected, and the perfusion area supplied by these arteries was excised using repeated ICG intravenous injection. This case of lung cancer with ABLL demonstrates that the repeated use of ICG can enable not only a precise upper segmentectomy but also accurate visualization and resection of a perfusion area supplied by aberrant arteries. more...

Background: Although most duodenal carcinomas are pathological adenocarcinomas, a small number of cases have been reported of adenosquamous carcinoma, characterized by variable combinations of two malignant components: adenocarcinoma and squamous cell carcinoma. However, owing to the small number of cases of non-ampullary duodenal adenosquamous carcinoma, there have been no reported cases of emergency pancreaticoduodenectomy for gastrointestinal hemorrhage due to non-ampullary duodenal adenosquamous carcinoma., Case Presentation: A 66-year-old Japanese male presented to the referring hospital with a chief complaint of abdominal pain, diarrhea, and dark urine that had persisted for 1 month. The patient was referred to our hospital because of liver dysfunction on a blood examination. Laboratory results of the blood on the day of admission showed that total and direct bilirubin levels (12.0 mg/dl and 9.6 mg/dl) were markedly increased. An endoscopic retrograde biliary drainage tube was inserted for the treatment of obstructive jaundice, and imaging studies were continuously performed. Contrast-enhanced computed tomography and endoscopy revealed an ill-defined lesion involving the second portion of the duodenum, predominantly along the medial wall, and measuring 60 mm in diameter. No metastases were observed by positron emission tomography. Pancreaticoduodenectomy was planned based on the pathological findings of poorly differentiated adenocarcinoma. However, 2 days before the scheduled surgery, the patient experienced hemorrhagic shock with melena. Owing to poor hemostasis after endoscopic treatment and poor control of hemodynamic circulation despite blood transfusion, radiological embolization and hemostasis were attempted but were incomplete. An emergency pancreaticoduodenectomy was performed after embolizing the route from the gastroduodenal artery and pseudoaneurysm area to reduce bleeding. The operation was completed using an anterior approach without Kocherization or tunneling due to the huge tumor. The operation time was 4 h and 32 min, and blood loss was 595 mL The pathological diagnosis was adenosquamous carcinoma. The postoperative course was uneventful with 17 day hospital stay and the patient is currently well, with no signs of recurrence 9 months after surgery., Conclusions: This report presents an extremely rare case of successful emergency pancreaticoduodenectomy for gastrointestinal hemorrhage caused by non-ampullary duodenal adenosquamous carcinoma., (© 2023. Japan Surgical Society.) more...

We herein report a 79-year-old woman who underwent surgery had recurred non-small cell lung cancer and developed irAEs following ICI treatment. During ICI treatment, we conducted monthly measurements of the serum antibody levels in this patient, including those which were both tumor- (anti-p53 antibody) and nonspecific (immunoglobulins). Anti-p53 antibodies and IgM had not increased during ICI treatment, but the serum levels of IgG and IgA had gradually increased before the occurrence of irAEs. These results suggest that monitoring serum immunoglobulin levels might enable the early detection of ICI-induced immune responses in patients with lung cancer., (© 2022 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.) more...

The efficacy and safety of immune checkpoint inhibitor (ICI) monotherapy in elderly patients with non-small cell lung cancer (NSCLC) remain unclear, especially in patients older than 80 years. We retrospectively reviewed the records of 10 patients older than 80 years with NSCLCs treated by ICIs. The median age was 85 years (range, 82-93 years), and 7 patients were men. The median length of follow-up was 13 months (range, 4.5-23 months). Eight patients had adenocarcinoma (3 of whom had exon 19 deletions), and two had squamous cell carcinoma. Expression of programmed cell death ligand 1 (PD-L1) was ≥ 50% in 3 patients, between 1% and 49% in 4 patients, < 1% in 1 patient, and undetected in 2 patients. Patients with undetected PD-L1 underwent transbronchial lung biopsy. Performance status was graded zero, one, and two in two, seven, and one patients, respectively. First-, second-, and third-line treatments were administered to three, three, and four patients, respectively. The 2-year overall survival rate was 30.0% (median, 285 days). Time to treatment failure rate on the 2 years was 10.0% (median, 167 days). One patient achieved a partial response, and one achieved a complete response. ICI-associated adverse events occurred in five patients. In summary, ICIs were effective in some patients older than 80 years; however, some experienced adverse effects. Elderly patients must be selected carefully for ICI treatment., Competing Interests: Nothing to disclose., (© 2021 The Authors. Aging Medicine published by Beijing Hospital and John Wiley & Sons Australia, Ltd.) more...

We herein report the case of a 62-year-old man who underwent extrapleural pneumonectomy (EPP) for pleural epithelial hemangioendothelioma (EHE) diagnosed by a pleural biopsy. Pre-operative computed tomography revealed diffuse pleural thickening and pleural effusion in the right thoracic cavity, although metastasis to neither the lymph nodes nor distant organs was detected. We decided to perform EPP based on surgical findings that the tumor had invaded the lung parenchyma. A pathological examination revealed tumor invasion of the lung parenchyma, blood vessel, pericardium, diaphragm and bronchial wall. Despite aggressive treatment, tumor recurrence was detected about 1 month after surgery. Although we controlled the tumor progression using pazopanib, the patient ultimately died 3.5 months after the operation. Pleural EHE is a very rare disease that has a poor prognosis due to its high malignant potential. It is important to formulate strategies matched to individual cases based on disease progression and invasiveness of treatment. more...

Introduction: Generally, lung cancer representing as Ground-glass nodules is associated with an early stage and good prognosis. However, we herein report a rare case of pure ground-glass nodules with mediastinal lymph node metastases., Presentation of Case: A 69-year-old man underwent video assisted thoracic surgery right upper lobectomy with mediastinal lymph node dissection due to multifocal Ground-glass nodules in the right upper lobe of the lung. Histopathologically, six lung adenocarcinomas were present simultaneously. Furthermore, we detected mediastinal lymph nodes metastases that contain micropapillary component. The lung lesion containing micropapillary component was a pure Ground-glass nodule that adjoining pulmonary bulla on CT findings., Discussion: Generally, lung cancer presenting as pure ground-glass nodules is associated with an early stage and good prognosis. However, the necessity of evaluating the mediastinal lymph nodes in pure ground-glass nodules is controversial. It is reported that lung cancer adjoining the wall of a bulla tends to have a poor prognosis, even when small in size. Therefore, Ground-glass nodules with metastases might have a different pathogenesis than other nodules., Conclusion: Adenocarcinoma appearing as pure Ground-glass nodules is associated with early stage lung cancer and a good prognosis. However, the findings in our patient indicate the importance and necessity of evaluating the mediastinal lymph nodes for metastases intraoperatively., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.) more...

Background: Several treatment strategies are available for primary spontaneous pneumothorax (PSP). Surgical procedures are also performed in patients with PSP without an absolute indication for surgery. This study was performed to investigate the best treatment strategy for PSP by comparison of the recurrence rate., Materials and Methods: From January 2006 to December 2013, 149 patients with PSP aged ≤50 years were treated in our institution. We reviewed the recurrence rate of PSP for each treatment strategy and evaluated the association between the recurrence rate of PSP with the clinicopathological characteristics. We also compared the surgery and non-surgery groups., Results: A significant difference in the PSP recurrence rate was found between the surgery and non-surgery groups (22% vs. 52%, respectively; p < 0.001), patients aged ≥22 and < 22 years (16% vs. 44%, respectively; p < 0.001), and smokers and nonsmokers (13% vs. 43%, respectively; p < 0.001). There were also significant differences in the multivariate analysis (p < 0.001, p = 0.050, and p = 0.001, respectively). In the surgery group, the PSP recurrence rate was significantly different between patients aged ≥22 and < 22 years (7% vs. 38%, respectively; p < 0.001) and smokers and nonsmokers (5% vs. 33%, respectively; p = 0.002). No significant differences were found in the non-surgery group., Conclusions: In the surgical treatment of PSP, it is desirable that smokers stop using tobacco and that patients are ≥22 years old. Moreover, when surgery is being considered, the best timing seems to be when air leakage is present because the air leakage sites can be resected. more...

Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Background: Although immune checkpoint inhibitors (ICIs) for non-small cell lung cancer (NSCLC) have been established as one of standard therapy, the prognostic factors of ICIs remain unclear, aside from the programed cell death-ligand 1 (PD-L1) expression of tumor cells. The aim of this study was to determine the prognostic factors of ICIs., Methods: We analyzed the clinicopathological data of 44 cases of advanced NSCLC targeted with ICIs in our hospital, between February 2016 and February 2018, in order to determine the prognostic factors of ICIs. We also reviewed the literature regarding ICIs., Result: We retrospectively analyzed the 44 cases (26 nivolumab and 18 pembrolizumab cases). These patients were 38 men and 6 women, comprising 13 cases of adenocarcinoma, 29 squamous cell carcinoma and 2 unclassified types. Seven patients were using first-line therapy and while the others were using second-line therapy or later. Epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) mutations were negative in all the cases. The response rate and disease control rate were 20.5% and 51.3%, respectively. The median progression-free survival time and median survival time were 146 days and 257 days, respectively. We observed five severe adverse effects (AEs) (three cases of interstitial pneumonia, one of liver dysfunction and one of adrenal failure), that were resolved by steroid pulse therapy. In multivariate analyses, the Eastern Cooperative Oncology Group performance status (ECOG PS), pathological type, standardized uptake value (SUV) on positron emission tomography (PET), white blood cell (WBC) count, neutrophil, neutrophil-to-lymphocyte ratio (NLR), lactate dehydrogenase (LDH) and albumin were independently prognostic factors. There were no significant differences in the prognosis between nivolumab and pembrolizumab., Conclusions: ICIs were effective in 44 treated NSCLC cases. Our analysis suggests that while ICIs are effective in treating patients, candidates must be carefully selected and cautiously observed., Competing Interests: Conflicts of Interest: F Tanaka has received lecture fees and received funds Chugai Pharmaceutical Co. Ltd., AstraZeneca Co. Ltd., Taiho Pharmaceutical Co. Ltd., MSD Co. Ltd. The other authors have no conflicts of interest to declare. more...

Detection of rare tumor cells circulating in the blood (CTCs) presents technical challenges. CellSearch, the only approved system for clinical use, fails to capture epithelial cell adhesion molecule-negative CTCs such as malignant pleural mesothelioma (MPM). We have developed a novel microfluidic device (CTC-chip) in which any Ab to capture CTCs is conjugated. The CTC-chip was coated with an Ab against podoplanin that is abundantly expressed on MPM. Circulating tumor cell-detection performance was evaluated in experimental models in which MPM cells were spiked in blood sampled from a healthy volunteer and in clinical samples drawn from MPM patients. The CTC-chip showed superior CTC-detection performance over CellSearch in experimental models (sensitivity, 63.3%-64.5% vs 0%-1.1%; P < .001) and in clinical samples (CTC-positivity, 68.8% vs 6.3%; P < .001). A receiver operating characteristic (ROC) analysis showed that the CTC test provided a significant diagnostic performance in discrimination of unresectable disease from resectable disease (area under the ROC curve, 0.851; P = .003). The higher CTC count (≥2 cells/mL) was significantly associated with a poor prognosis (P = .030). The novel CTC-chip enabled sensitive detection of CTCs, which provided significant diagnostic and prognostic information in MPM., (© 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.) more...

Introduction: Thymic papillary adenocarcinoma is rare. Further, thymic papillary adenocarcinoma coexisting with type A thymoma is extremely rare. Surgery remains the only effective treatment for this disease., Presentation of Case: An 84-year-old Japanese woman presented to our institute due to abnormal chest computed tomography (CT) findings showing a 45 × 40 × 40-mm tumor located in the anterior mediastinum. A malignant tumor was suspected based on the CT findings and high serum levels of carcinoembryonic antigen. Mediastinal tumor resection was performed via video-assisted thoracic surgery through the left thoracic approach. This patient was discharged from our institute without any problems at six days post-operation., Discussion: This report has three major implications. First, one of the tumors was papillary adenocarcinoma. Primary papillary adenocarcinoma of the thymus is exceedingly rare. Second, papillary adenocarcinoma and type A thymoma coexisted in this tumor. Third, epithelial thymic tumor should be resected completely, since complete resection has been reported to be associated with an improved prognosis., Conclusion: We encountered a rare case of thymic papillary adenocarcinoma coexisting with type A thymoma., (Copyright © 2019 The Author(s). Published by Elsevier Ltd.. All rights reserved.) more...

Background: The standard therapy for brain metastasis (BM) in non-small cell lung cancer (NSCLC) is radiation therapy (RT), although it is associated with complications such as leukoencephalopathy. In the current report, we retrospectively review data from eight patients who had NSCLC and harbored epidermal growth factor receptor (EGFR) mutations, and who were received erlotinib plus bevacizumab (E+B) as first-line therapy for BM., Methods: Patients were given E+B as first therapy for BM until August 2017 at our institution. Patients receiving local therapy for BM, such as surgery or radiotherapy, were excluded. Patients were administered erlotinib orally (once daily at 150 mg/body) plus bevacizumab by intravenous infusion (15 mg/kg on day 1 of a 21- or 28-day cycle)., Results: Eight NSCLC patients who were diagnosed with BM received E+B, including 2 men and 6 women with a median age of 65 years (range, 46-84 years). Four patients had an L858R EGFR mutation, while the other four had an exon 19 deletion. Seven patients had a partial response to E+B treatment, and one had a complete response. The 2-year survival rate was 62.5%. Three patients who were pre-treated with gefitinib had an E+B treatment duration of less than 1 year. At the time of this analysis, four patients had BM-related neurologic symptoms and multiple BMs, and were still receiving E+B with no evidence of treatment failure after more than 1 year., Conclusions: E+B can be used as first-line therapy for BM, even in patients with BM-related neurologic symptoms and multiple BMs., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare. more...

Introduction: Patients with undiagnosed anterior mediastinal tumors commonly undergo surgery for diagnosis and treatment. However, determining the optimal therapeutic strategy is difficult for tumors with substantial invasion, such as lesions touching the aortic arch (AA)., Case Presentation: A 76-year-old man of Asian descent presented to our hospital because chest computed tomography (CT) revealed an anterior mediastinal tumor. This tumor surrounded the left subclavian vein and touched the AA. We suspected the tumor to be malignant. We therefore decided to resect the tumor with preparation for total arch replacement (TAR). The operation was performed in three steps. First, we performed a mediastinal sternotomy. However, the tumor had invaded the subclavian vein, so we resected this vein after adding a transmanubrial approach. However, because of invading the AA we needed next step. Second, we shifted the patient to the right lateral decubitus position. We performed partial resection of the left upper lobe and exfoliated the distal AA. Third, we shifted the patient to the dorsal position and implanted an artificial cardiopulmonary device, after which we performed TAR, and pulmonary artery (PA) trunk plasty with a pericardial patch. The operation was successful, with no major adverse events. Pathologically, the tumor was diagnosed as diffuse large B-cell lymphoma., Discussion: If oncologically complete resection is preferable for tumors with substantial invasion, complete resection should be attempted even if the surgery is difficult., Conclusion: We performed complete resection of an anterior mediastinal tumor with TAR and PA trunk plasty using a pericardial patch. more...

Background: Thymic carcinoma is uncommon, presents locally at an advanced stage, and behaves aggressively. The optimum treatment for advanced thymic carcinoma is controversial. We retrospectively reviewed our institutional experience with patients with thymic carcinoma., Methods: We analyzed the clinical data of six patients who underwent total thymectomy for thymic carcinoma at our institution from 2006 to 2016. Variables analyzed included sex, age, histological classification, Masaoka staging, postoperative treatment, and recurrence., Results: The clinical characteristics of the six patients with thymic carcinoma (median age, 56 years; five men and one woman) were as follows: squamous cell carcinoma (n=5); sarcomatoid carcinoma (n=1); Masaoka stages II (n=1), III (n=2), IVa (n=1), and IVb (n=2). Four patients underwent combined pulmonary resection (66.7%) as a component of en bloc resection due to suspicion of pulmonary invasion. Four patients (66.7%) received postoperative therapy, and complete resection was achieved for four patients. There were no perioperative deaths. One patient experienced a recurrence., Conclusions: Complete resection for thymic cancer improved the prognosis of our patients, indicating that robust studies will be required to confirm our findings., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare. more...

Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Background: The detection of extremely small lung tumors has increased with the development of computed tomography. Resection of such tumors by thoracoscopy is often hindered due to the unclear location of the tumor. Various methods of preoperative determination of such lesions have been attempted, but without marked success. Here we used virtual-assisted lung mapping (VAL-MAP) to perform surgical resection of small lung lesions., Methods: We selected patients with pulmonary tumors that we anticipated to be difficult to identify during thoracoscopy and/or decide the resection line for sub-lobar lung resection. The wedge resections in the VAL-MAP group were compared to a group of patients who underwent wedge resection without VAL-MAP in 2013., Results: Surgery duration was significantly shorter in the VAL-MAP group (average: 76.4 min) than in the 2013 group (average: 108.6 min; P=0.000451), although the VAL-MAP group (average major axis: 9.6 mm) had smaller tumors (P=0.000032) and more pure ground-glass opacities (GGOs) (P=0.0000919) than the 2013 group (average major axis: 16.6 mm)., Conclusions: The findings of this study indicate that VAL-MAP is efficacious. In particular, VAL-MAP resulted in a shorter surgery duration and has expanded the indications of resectable lesions., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare. more...

Malignant mesothelioma (MM) is a highly aggressive malignant tumor, predominantly associated with job-related exposure to asbestos. Development of effective and non-invasive modalities for diagnosis is an important issue in occupational medicine. Circulating tumor cells (CTCs), which are tumor cells that are shed from primary tumors and circulate in the peripheral blood, may be detected at an earlier stage than malignant tumors, and detection of CTCs may provide a novel insight into the diagnosis of MM. In a previous study evaluating clinical utility of CTCs, detected with a widely used system 'CellSearch', the authors indicated a significant however insufficient capability in the diagnosis of MM, suggesting need for a more sensitive system. Accordingly, the authors developed a novel microfluidic system to capture CTCs (CTC-chip), and demonstrated that the CTC-chip effectively captured MM cells (ACC-MESO-4) spiked in the blood by conjugating an anti-podoplanin antibody. The results of the present study demonstrated that the CTC-chip coated with the anti-podoplanin antibody captured another MM cell (ACC-MESO-1). However, the capture efficiencies were lower than those for ACC-MESO-4. In addition, an anti-mesothelin antibody was used to capture CTCs, however the CTC-chip coated with the anti-mesothelin antibody failed to effectively capture MM cells, possibly due to low mesothelin expression. Overall, the CTC-chip may capture specific types of CTCs by conjugating any antibody against an antigen expressed on CTCs, and may be a useful system for the diagnosis of malignant tumors, including MM. more...

Background: Malignant pleural mesothelioma (MPM) is an uncommon malignant tumor, and its synchronous occurrence with primary lung cancer is extremely rare. Here, we report the first surgical case of synchronous MPM and contralateral lung adenocarcinoma. Extrapleural pneumonectomy (EPP) combined with surgery for contralateral lung cancer may not be tolerated, and a lung-sparing procedure including pleurectomy/decortication (P/D) can be an alternative to achieve complete resection., Case Presentation: A 69-year-old male with right MPM and lung adenocarcinoma in the left upper lobe presented. Two lesions were judged to be synchronous MPM and lung cancer that were both potentially resectable clinical stage I diseases, and complete resection of both tumors was successfully achieved with right P/D following left upper division segmentectomy., Conclusions: P/D, not EPP, is a less invasive surgical procedure for MPM with curative intent and can be performed in combination with contralateral lung resection. more...

Background: The standard treatment for patients with stage IV non-small cell lung cancer (NSCLC) is systemic chemotherapy. However, certain patients, such as those with oligometastasis or M1a disease undergo resection of the primary lesion., Methods: We conducted a retrospective review of the records of 1,471 consecutive patients with NSCLC who underwent resection of the primary lesion for between June 2005 and May 2016. The present study included 38 patients with stage IV NSCLC who underwent complete resection of the primary lesion as first-line treatment., Results: The median follow-up duration for the 38 patients (27 men) was 17.7 months (range, 1-82.3 months). The T factors were T1/T2/T3/T4 in 4/16/12/6 patients, respectively. The N factors were N0/N1/N2/N3 in 16/8/12/2 patients, respectively. The M factors were M1a/M1b/M1c in 19/13/6 patients, respectively. Of the 19 M1a patients, 11 were classified as cM0. We introduced the novel classification M-better/M-worse. M-better includes cM0 patients and M1b and M1c patients in whom all lesions have been locally controlled. M-worse includes cM1a patients and M1b and M1c patients in whom lesions cannot be locally controlled. The new M-better/M-worse statuses were 24/14 patients, respectively. The histology of NSCLC was adenocarcinoma/squamous cell carcinoma/others in 30/5/3 patients, respectively. The 5-year overall survival rate was 29%, and the median survival time was 725 days. Squamous cell carcinoma and M-worse were significant factors predicting poor outcomes (P=0.0017, P=0.0007, respectively)., Conclusions: Even for stage IV NSCLC patients, resection of the primary lesion may be beneficial, especially for those with M-better status and those not diagnosed with squamous-cell carcinoma (SCC)., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare. more...

Background: We actually investigated the surgical and pathological findings in cases which tumor invasion of the major thoracic vessels was suspected based on the preoperative Computed tomography (CT) findings., Materials and Methods: We retrospectively reviewed our prospective database of all patients, who underwent lung resection for lung cancer from 2012 to 2014. 387 patients underwent lung cancer surgery. Among these patients, we analyzed 30 patients in whom pulmonary artery (PA) invasion was suspected and 11 patients in whom pulmonary vein (PV) or left atrium (LA) invasion was suspected based on the preoperative CT findings., Results: Among the 30 patients with suspected PA invasion, there were 9 patients in whom the tumor could be peeled off the PA in actual thoracotomy. Pathological invasion of the PA was observed in 6 of these patients. The positive predictive value of the preoperative CT findings was 20%. Among the 11 patients with suspected PV or LA invasion, there were 2 patients in whom the tumor could be peeled off the PV or LA in actual thoracotomy. Pathological tumor invasion of the PV or LA was observed in 4 of these patients. The positive predictive value of the preoperative CT findings was 36%., Conclusion: The positive predictive value of the preoperative CT findings for tumor invasion of the thoracic vessels was low. Therefore, surgical opportunities that offer the chance of a cure shouldn't be missed in advanced lung cancer patients because the tumor is located near the major thoracic vessels on preoperative CT. more...

Background: Treatment of tracheostenosis after tracheostomy in pediatric patients is often difficult. Mucopolysaccharidosis is a lysosomal storage disease that may induce obstruction of the airways., Case Presentation: A 16-year-old male patient underwent long-term follow-up after postnatal diagnosis of type II mucopolysaccharidosis. At 11 years of age, tracheostomy was performed for mucopolysaccharidosis-induced laryngeal stenosis. One week prior to presentation, he was admitted to another hospital on an emergency basis for major dyspnea. He was diagnosed with tracheostenosis caused by granulation. The patient was then referred to our institution. The peripheral view of his airway was difficult because of mucopolysaccharidosis-induced tracheomalacia. For airway management, a mediastinal tracheostoma was created with extracorporeal membrane oxygenation. To maintain the blood flow, the skin incision for the mediastinal tracheal hole was sharply cut without an electrotome. The postoperative course was uneventful, and the patient was weaned from the ventilator on postoperative day 19. He was discharged 1.5 months postoperatively. Although he was referred to another institution because of respiratory failure caused by his primary disease 6 months postoperatively, his airway management remained successful for 1.5 years postoperatively., Conclusion: Mediastinal tracheostomy was useful for treatment of tracheostenosis caused by granulation tissue formation after a tracheostomy. more...

Introduction: Superior sulcus tumors, frequently referred to as Pancoast tumors, are a wide range of tumors invading a section of the apical chest wall called the thoracic inlet. For this reason, a surgical approach and complete resection may be difficult to accomplish. We experienced a locally advanced superior sulcus tumor (SST) located from the anterior to posterior apex thoracic inlet and performed complete resection after definitive chemoradiation., Presentation of Case: A 71-year-old Japanese male presented at our hospital due to left back pain and an abnormal chest computed tomography (CT) scan showing 80×70×60-mm tumor located in the left middle apex thoracic inlet. This tumor was located near the subclavian artery, and the subclavian lymph nodes were swollen. The tumor was found to be an adenocarcinoma (clinical-T3N3M0 stage IIIB). Therefore, we performed definitive chemoradiation therapy. Slight reduction in the tumor size was noted after the treatment, and the subclavian lymph nodes were not swollen. We next performed surgical resection for this SST. Regarding the surgical approaches, the anterior approach was a transmanubrial approach, and the posterior approach was a Paulson's thoracotomy. In this manner, we were able to perform complete en-bloc resection of this tumor., Discussion: This surgical approach was effective and safe for treating a SST located from the anterior to posterior apex of the thoracic inlet. The patient remains healthy and recurrence-free at 2.5 years after the operation., Conclusion: Surgical approach for SST is difficult. Therefore, this approach is effective and safety., (Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.) more...

Capture of circulating tumor cells (CTCs), which are shed from the primary tumor site and circulate in the blood, remains a technical challenge. CellSearch® is the only clinically approved CTC detection system, but has provided only modest sensitivity in detecting CTCs mainly because epithelial cell adhesion molecule (EpCAM)-negative tumor cells may not be captured. To achieve more sensitive CTC‑capture, we have developed a novel microfluidic platform, a 'CTC-chip' comprised of light-curable resins that has a unique advantage in that any capture antibody is easily conjugated. In the present study, we showed that EpCAM-negative tumor cells as well as EpCAM-positive cells were captured with the novel 'universal CTC-chip' as follows: i) human lung cancer cells (PC-9), with strong EpCAM expression, were efficiently captured with the CTC-chip coated with an anti-EpCAM antibody (with an average capture efficiency of 101% when tumor cells were spiked in phosphate‑buffered saline (PBS) and 88% when spiked in blood); ii) human mesothelioma cells (ACC-MESO-4), with no EpCAM expression but with podoplanin expression, were captured with the CTC-chip coated with an anti-podoplanin antibody (average capture efficiency of 78% when tumor cells were spiked in PBS and 38% when spiked in blood), whereas ACC-MESO-4 cells were not captured with the CTC-chip coated with the anti-EpCAM antibody. These results indicate that the novel 'CTC-chip' can be useful in sensitive EpCAM-independent detection of CTCs, which may provide new insights into personalized medicine. more...

Introduction: Postoperative pulmonary embolism (PE) is the one of the most important complications after thoracic surgery. This complicatin after the surgery is often treated by new anticoaglant drug, such as rivaroxaban, which dose not need to the monitoring of blood coaglation system. We experienced postoperative bleeding case during anticoaglant therapy using rivaroxaban., Presentation of Case: The patient underwent a right upper lobectomy with lung and chest wall resection for lung cancer. On postoperative day (POD) 10, we started to use rivaroxaban to treat the deep vein thrombosis (DVT). Four days after starting the rivaroxaban treatment, severe surgical site hemorrhage occurred, which led to the need for the infusion of concentrated red cells (CRC). After stopping the rivaroxaban, the thoracic bleeding ceased. Because the event occurred so long after the surgery, and because the bleeding stopped after withdrawal of treatment, we believe that rivaroxaban induced the thoracic bleeding., Conclusion: Some reports in the field of orthopedics (Turpie et al., 2009) have noted that rivarxaban is effective to prevent postoperative DVT. However, there were few reports that invied the attention to postoperative bleeding be induced by rivarxaban. Thus, we describe this case in order to alert clinicians to the potential bleeding risks associated with the admistration of rivaroxaban postoperatively., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.) more...

Background: Resection and reconstruction of the pulmonary artery during lobectomy is a safe and effective procedure for centrally located lung cancer. We usually choose a pericardial conduit to repair a large defect of the pulmonary artery. The use of an autologous pulmonary vein conduit for reconstruction was first described in 2009., Case Presentation: A 64-year-old woman with left upper lung adenocarcinoma with mediastinal and hilar adenopathy was referred to our hospital. Hilar nodes had extensively infiltrated the pulmonary artery. We interposed an autologous superior pulmonary vein between the cut ends of the pulmonary artery. She was discharged without any complication on the ninth postoperative day., Conclusions: A pulmonary vein conduit is a good option for reconstruction of the pulmonary artery. We report the successful use of an autologous pulmonary vein conduit. more...

Background: Pleomorphic lung cancer cells have been reported to produce cytokines, resulting in systemic reactions. Recently, the autonomous production of hematopoietic cytokines (granulocyte colony-stimulating factor [G-CSF], granulocyte-macrophage colony-stimulating factor [GM-CSF], and interleukin-6 [IL-6]) was observed in some of these patients., Case Presentation: We herein report a case of complete resection of right pleomorphic lung cancer producing IL-6. The patient had a high-grade fever before surgery, and a blood examination showed high IL-6 and CRP levels in the serum. After surgery, the patient no longer had a fever, and the elevated serum IL-6 levels had dropped to values less than those before the operation. Immunohistochemically, the carcinoma cells were faintly or focally positive for IL-6 and negative for G-CSF., Conclusions: The symptoms in the present case were dramatically improved by surgery. In addition, an immunohistochemical examination showed that the cancer cells were positive for IL-6. more...

Competing Interests: The authors have no conflicts of interest to declare.

Sarcomatoid carcinoma of the thymus is extremely rare. An operation remains the only effective treatment for this disease. We report a case of complete resection of thymic sarcomatoid carcinoma through a total aortic arch replacement and left upper lobectomy at our institution. Our aggressive operation was very effective, and the patient has experienced no recurrence in the 3 years since his operation., (Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.) more...

Background: Thymic carcinomas are usually detected in the anterior mediastinum. Thymic carcinoma occurring in the middle mediastinum and showing an image of a cyst is extremely rare., Case Presentation: A 64-year-old man with a middle mediastinal tumor detected incidentally by a CT scan was referred. Chest CT showed an entirely cystic mass in the middle mediastinum between the bilateral brachiocephalic vein and trachea. We resected the tumor completely in the right recurrent nerve because it had invaded the nerve. Immunohistochemical features showed a thymic carcinoma pattern. The final diagnosis was thymic squamous cell carcinoma occurring in the middle mediastinum., Conclusion: To our best knowledge, this is the first report of a thymic carcinoma occurring in the middle mediastinum, as demonstrated by histopathological findings with immunohistochemical features. more...

Background: Surgery for lung cancer invading the spine remains challenging associated with high morbidity and mortality. However, recent advances in surgical techniques as well as in perioperative care may improve outcomes of lung cancer surgery with vertebrectomy. We describe our surgical approach and assess the outcome lung cancer invading the spine., Methods: We retrospectively reviewed our recent experiences of lung cancer with vertebral invasion, in which we have performed total or partial vertebrectomy from January 2011 through April 2015., Results: We experienced eight patients who were treated with partial or total vertebrectomy for lung cancer. Vertebral invasion was evaluated by chest CT and MRI findings. All cases were no distant metastasis. N factors were all patients N0 revealed by chest CT and PET-CT. Two patients were treated preoperative induction therapy (CDDP + TS-1, Radiation 50 Gy). For the surgery, total vertebrectomy was performed two patients, hemi vertebrectomy was two patients, transverse-process resection was four patients. In all of eight cases, complete resection were perfomed with total or partial vertebrectomy. Morbidity was observed in six patients (75%); no mortality occurred. Six patients (75%) were survived after surgery (range: 12-62 months) and four patients (50%) were no recurrence. Five years overall survival rate was 71.4%., Conclusions: In our experience, Lung cancer surgery combined with vertebrectomy is highly aggressive surgery associated with high morbidity. But, this procedure is a promising treatment option for selected patients, for example N0M0 disease with lung cancer invading the spine. more...

Tyrosine kinase inhibitors (TKIs) of the epidermal growth factor receptor (EGFR) may achieve long-term survival in selected cases with advanced non-small cell lung cancer harboring activating mutations in the EGFR gene, but a cured case has not been reported yet. Here, we present the first case of EGFR -mutated lung adenocarcinoma cured with an EGFR-TKI, as the 75-year-old Japanese man has achieved complete response with gefitinib treatment and has survived without tumor 10 years after termination of gefitinib treatment. more...

BACKGROUND Circulating tumor cells (CTCs) are tumor cells that are shed from primary tumors and circulate in the peripheral blood. CTCs, as a surrogate of micro-metastasis, can be a useful clinical marker, but their clinical significance remains unclear in lung cancer. We now report a case of lung cancer in which the count of CTCs was useful in monitoring postoperative recurrence. CASE REPORT A 50-year-old man had undergone right upper lobectomy for lung cancer (pT1bN2M0, stage IIIA adenocarcinoma), followed by cisplatin-based adjuvant chemotherapy. After the patient's operation, we initiated monitoring of CTCs using CellSearch, and documented the change in the CTC count along with the development of cancer recurrence and response or progression to chemotherapy given for recurrent disease. CONCLUSIONS The CTC count may be useful in monitoring blood of patients with lung cancer. more...

We herein present the pathological findings of a bulla covered using an absorbable polyglycolic acid sheet applied with fibrin glue. These findings indicated that the membrane of the bulla was reinforced. Covering the bulla with an absorbable polyglycolic acid sheet (Neoveil, Gunze Ltd, Kyoto, Japan) and applying fibrin glue was effective to prevent the recurrence of the pneumothorax. Moreover, this report is the first case report showing the pathological findings of a bulla which was covered with an absorbable polyglycolic acid sheet and fibrin glue. more...

Background: Open window thoracotomy (OWT) as well as its closure are challenging. Transposition of omental pedicle and muscle flaps is often performed for OWT closure; however, the better technique among the two is unknown. The purpose of this series was to evaluate the outcomes of using both omental pedicle and muscle flaps for the aforementioned closure., Methods: This was an observational retrospective cohort study on 27 consecutive patients who underwent OWT closure at a single institution between January 2005 and December 2014. The operation was performed using either omental pedicle or muscle flap with thoracoplasty. We compared both techniques in terms of the patient background [sex, age, body mass index (BMI) and C-reactive protein (CRP) before OWT and serum albumin levels before OWT closure], presence of methicillin-resistant Staphylococcus aureus (MRSA) infection, rate of bronchopleural fistula (BPF), duration of OWT, recurrence of local infection, morbidity, duration of indwelling drainage after operation, success, mortality and postoperative hospital stay., Results: There were 9 (33.3%) omental pedicle flap procedures and 18 (66.7%) muscle flap procedures. The rate of local recurrence after closure of OWT was significantly higher with muscle flap than with omental pedicle flap (0% vs. 50.0%, P=0.012). The median duration of postoperative hospital stay was significantly shorter with omental pedicle flap than that with muscle flap (16.0 vs. 41.5 days, P=0.037). Mortality was observed in 2 patients (11.2%) in the muscle flap group and no patient in the omental pedicle flap group. Success rate was similar between the two groups (100% for omental pedicle flap vs. 83.3% for muscle flap)., Conclusions: Omental pedicle flap was superior to muscle flap in terms of reducing local recurrence and shortening postoperative hospital stay. However, mortality, morbidity and success rates were not affected by the choice of flap. more...

Introduction: Surgery for primary lung cancer invading the spine remains challenging. Here, we present a case of superior sulcus tumor (SST) with vertebral invasion, successfully resected with total vertebrectomy (Th2) and dissection of involved apical chest wall and the subclavian artery (SCA)., Presentation of Case: A 62-year-old man was referred with the diagnosis of lung squamous cell carcinoma originating from left upper lobe (clinical stage IIIA/T4N0M0) involving the thoracic vertebrae (Th2) as well as the apical chest wall including three ribs (1st, 2nd and 3rd) and SCA. After induction concurrent chemo-radiotherapy, we achieved complete resection by three-step surgical procedures as follows: first, the anterior portion of involved chest wall including SCA was dissected through the trans-manubrial approach (TMA); next, the posterior portion of involved chest wall including ribs was dissected and left upper lobectomy with nodal dissection was performed through posterolateral thoracotomy; finally, total vertebrectomy (Th2) was performed through posterior mid-line approach., Discussion: This tumor was existence of anterior and posterior position in pulmonary apex region. So that, it is very important for complete resecting this complicated tumor to work out operation's strategy., Conclusion: Surgery may be indicated for SST invading the spine, when complete resection is expected., (Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.) more...

Background/objectives: CD44 is often expressed in various types of tumor cells and involved in a number of biological behaviors of malignancy. The present study focused on the clinical significance of the expression of CD44st and CD44v6 in non-small cell lung cancer (NSCLC)., Methods: The cohort consisted of 261 consecutive patients who had undergone complete resection of NSCLC. CD44 expression was evaluated in surgical specimens by immunohistochemical staining. Serum CD44 levels were determined using a sandwich ELISA (enzyme-linked immunosorbent assay)., Results: In the immunohistochemical analysis, significant correlations were observed between CD44 expression and clinicopathological factors such as the T factor, N factor, pathological stage, and histological type. The 5-year survival rates according to CD44v6 expression were 65.8 and 80.6% in the higher and lower expression groups, respectively (p = 0.0053). According to ELISA, the group with higher expression of serum CD44v6 also showed a significantly more unfavorable prognosis than the lower expression group (p = 0.014). According to multivariate analysis using these significant variables, serum CD44v6 level was found to be an independent prognostic factor (p = 0.048)., Conclusions: CD44v6 overexpression and higher serum CD44v6 levels were found to be significantly unfavorable prognostic factors., (© 2016 S. Karger AG, Basel.) more...

Background: Postoperative recurrence is a significant problem associated with a poor prognosis. However, there is currently no consensus regarding biomarkers of recurrence., Materials and Methods: We performed a microarray expression analysis using a combination of tumor tissues (n=2) and cell lines. We prioritized and validated candidate protein expression levels in the primary tumors., Results: We prioritized 18 genes found to be up-regulated by more than four-fold in both A925LPE3 cell lines compared to the A925L cell line (lung adenocarcinoma) and in the cases of recurrence versus no recurrence, in order to find genes highly causative of metastasis. Among them, we selected transmembrane protease, serine 4 (TMPRSS4) and identified positive expression of TMPRSS4 in 93 (57.8%) patients. A significant negative association was observed only between the TMPRSS4 expression level and the N status. The univariate logistic regression models indicated that TMPRSS4 expression was an independent predictor of recurrence, as was the T and N status., Conclusion: TMPRSS4 expression is associated with postoperative recurrence. In addition, the current survival curves demonstrated that TMPRSS4 expression is associated with statistically significant differences in survival among patients with lung adenocarcinoma. TMPRSS4 staining can be used to predict the prognosis of such patients after surgery., (Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.) more...