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There is no standard program for laparoscopic surgery training in Japan, and competency in these procedures does not require the acquisition of board certification. The purpose of this survey was to investigate the current status of laparoscopic surgery training in Japan. A questionnaire survey was mailed to 2296 members of the Japan Society for Endoscopic Surgery who were between postgraduate year 3 and 10. The questionnaire inquired about laparoscopic surgical training conditions, operation case numbers, and autonomy in eight laparoscopic procedures. The total response rate was 28.1%. The number of cases required to perform procedures independently was demonstrated. Most participants felt confident in performing laparoscopic appendectomy and cholecystectomy; however, they felt less confident about performing laparoscopic colectomy and gastrectomy. The information from this survey may be useful for surgical educators, surgical societies, and the board certification council for rebuilding the surgical training system in Japan.

Anastomotic leakage is one of the major complications that can occur after an esophagectomy. Usually, preemptive surgical intervention with prompt open drainage by cervical incision is the first choice. In our department, on the other hand, we perform intraluminal continuous decompression (ILCD) using a computer-controlled portable vacuum pump system (Thopaz®) as first-line therapy for leakage of the cervical anastomosis. In this study, we examine the effectiveness of this management. Methods Thirty-eight patients who underwent esophagectomy and cervical anastomosis and were diagnosed with leakage between May 2005 and October 2019, were studied. Until July 2014, cervical incision was generally performed, and ILCD or nasoesophageal extraluminal drainage (NEED) was added in some cases (conventional group). Since August 2014, we have performed ILCD and have added NEED in patients for whom ILCD was ineffective. A cervical incision was made for refractory cases (ILCD group). These two groups were analyzed statistically. Fifteen (39.5%) of the 38 patients were treated as the conventional group, and the remaining 23 (60.5%) were treated as the ILCD group. Results Thirteen patients in the conventional group (86.7%) required a cervical incision. Eight patients in the ILCD group (34.8%) underwent cervical incision and 9 (39.1%) underwent NEED. Drinking water orally was resumed at a median (range) of 35 (6–284) days from leakage in the conventional group and 18 (0–111) days from leakage in the ILCD group. The time to oral drinking was significantly shorter in the ILCD group (p = 0.0365). Six patients in the conventional group (40%) and one patient in the ILCD group (4.3%) had Clavien-Dindo IIIb or higher complications, indicating a significantly lower rate in the ILCD group (p = 0.0096). Conclusion The ILCD as first-line therapy is a minimally invasive treatment that effectively prevents exacerbation of leakage after subtotal esophagectomy.

Thoracoscopic esophagectomy (TE) requires advanced surgical skills. Learning TE only through conventional on-the-job- training (OnJT) is difficult. Therefore, it is necessary to establish a safe and efficient educational program to learn the procedure. In our department, cadaver surgical training (CST) has been used to learn our standard procedure of prone position TE. In this presentation, we describe the usefulness of CST as an education tool for the surgical training of TE. Methods Cadavers embalmed by Thiel fixation were used for the training. To be eligible, the trainee must possess the surgical skills to perform laparoscopic gastrectomy and have the motivation to perform TE. Our program included self-study and lectures and evaluating the trainee using our original manual and evaluation sheet. During the CST practice, one cadaver was assigned to each trainee, and the trainee experienced whole procedure both as the operator and the assistant. After the training, feedback was given using the same evaluation sheet. Results Ten surgeons were evaluated using the technical evaluation sheet (12 items, 5 points per item, total 60 points), the average of the total points increased from 23 to 43 points after the training. The item with largest increase and highest score after the training was “thoracic duct dissection” (1.8 to 4.0). The item “Left recurrent laryngeal nerve (RLN) dissection” was the worst in both pre- and post-training as the average score was only increased from 1.6 to 3.1. On the other hand, the item “Right RLN dissection” score showed a moderate change from 1.7 to 3.5. Conclusion CST for mastering the whole surgical procedure of TE was useful in terms of overall quality of the operative performance. On the other hand, it seemed to be insufficient for mastering the lymph node dissection around the left recurrent laryngeal nerve. Development of a comprehensive education program combined with learning the whole procedure by CST and repetition training for a highly difficult procedure by simulation is necessary.

Postoperative pancreatic fistula (POPF) after pancreatectomy is one of the severe postoperative adverse events. We aimed to clarify the outcomes of a strategy for POPF after left-sided pancreatectomy with one-step endoscopic ultrasonography-guided drainage (EUSD) and percutaneous drainage (PCD) based on the wall status of collected fluid.From January 2012 to September 2017, 90 of 336 patients developed grade B/C POPF and were retrospectively analyzed. Primary outcome measures were the technical and clinical success and resolution rates. Secondary outcome measures were time from surgery to intervention, and time from intervention to discharge/resolution or stent/tube removal and adverse events.Seventeen patients underwent EUSD and 73 patients underwent PCD for POPF. The technical success rates were 100% in both the EUSD and PCD groups. The clinical success and resolution rates in the EUSD group were 100%, while those in the PCD group were 98.6%. The time from surgery to intervention was significantly longer in the EUSD group than in the PCD group (20 vs. 11 days, p0.001). The time from intervention to discharge/resolution was significantly shorter in the EUSD group than in the PCD group (11 vs. 22 days, p0.001/10 vs. 20 days, p0.001). The time from intervention to stent/tube removal was significantly shorter in the PCD group than in the EUSD group (20.5 vs. 873 days, p0.001). Adverse event rates were similar in the two groups (11.8% vs. 5.5%).A drainage strategy for POPF based on the wall status of collected fluid is appropriate.

Previous studies have shown that curative resection (R0 resection) was among the most crucial factors for the long-term survival of patients with PHCC. To achieve R0 resection, we performed the transhepatic direct approach and resection on the limits of division of the hepatic ducts. Although a recent report showed that the resection margin (RM) status impacted PHCC patients’ survival, it is still unclear whether RM is an important clinical factor. To describe a technique of transhepatic direct approach and resection on the limit of division of hepatic ducts, investigate its short-term surgical outcome, and validate whether the radial margin (RM) would have a clinical impact on long-term survival of perihilar cholangiocarcinoma (PHCC) patients. Consecutive PHCC patients (n = 211) who had undergone major hepatectomy with extrahepatic bile duct resection, without pancreaticoduodenectomy, in our department were retrospectively evaluated. R0 resection rate was 92% and 86% for invasive cancer-free and both invasive cancer-free and high-grade dysplasia-free resection, respectively. Overall 5-year survival rate was 46.9%. Univariate analysis showed that preoperative serum carcinoembryonic antigen level (> 7.0 mg/dl), pathological lymph node metastasis, and portal vein invasion were independent risk factors, but R status on both resection margin and bile duct margin was not an independent risk factor for survival. The transhepatic direct approach to the limits of division of the bile ducts leads to the highest R0 resection rate in the horizontal margin of PHCC. Further examination will be needed to determine the adjuvant therapy for PHCC to improve patient survival.

Diagnosing peritoneal dissemination is essential for selecting the appropriate therapeutic strategy for patients with pancreatic cancer. Intraoperative laparoscopic diagnosis enables the selection of less invasive surgical strategies. Photodynamic diagnosis using 5-aminolevulinic acid may improve gastrointestinal cancer diagnostic accuracy, although weak fluorescence is not easily detected. Here we aimed to improve this sensitivity using laparoscopic spectrophotometry.Photodynamic diagnosis was performed using serial dilutions of protoporphyrin IX, and its detectability using laparoscopic spectrophotometry was compared with that using naked-eye observation. Five-aminolevulinic acid-photodynamic diagnosis was performed for pancreatic cancer cell lines, and a murine peritoneal disseminated nodule model was established. We compared laparoscopic spectrophotometry and naked-eye observation results using white and fluorescent lights and compared them to routine histopathological examination results. Photodynamic diagnoses were made in 2017 and 2018 in eight patients with pancreatic cancer.Weaker fluorescence of the diluted protoporphyrin IX samples was better detected with spectrophotometry than with naked-eye observation. Moreover, a spectrograph of protoporphyrin IX in multiple cell lines was detected by spectrophotometry. In the murine model, the detection rates were 62 %, 78 %, and 90 % for naked-eye observation with white light, fluorescent light, and spectrophotometry, respectively. Comparisons of fluorescent light-negative peritonea with and without pathological metastases showed significantly higher spectrophotometric intensities in the former (P0.010). In clinical studies, three fluorescent light-negative spectrophotometry-positive pathologically metastatic lesions were observed.Laparoscopic spectrophotometry in the murine model and extraperitoneally photodynamic diagnoses using spectrophotometry in clinical practice are sensitive photodynamic diagnostic techniques.

Objective Pembrolizumab has benefited patients with advanced non-small-cell lung cancer (NSCLC) with a programmed death-ligand (PD-L) 1 high expression, but little information is available regarding its safety for patients with interstitial lung disease (ILD). The aim of this study was to assess the efficacy and tolerability of pembrolizumab for patients with advanced NSCLC and preexisting ILD. Methods We retrospectively reviewed the medical records of five patients with advanced NSCLC and preexisting ILD who received pembrolizumab monotherapy in a first-line setting. Patients All patients had mild ILD and pulmonary emphysema with a forced vital capacity within the normal range. Pembrolizumab was administered at a dose of 200 mg/body on day 1 every 3 weeks. Results The overall response rate was 60%. Four patients developed pembrolizumab-induced lung injury, which was improved in all cases by corticosteroid therapy. One patient received pembrolizumab for two years, did not experience lung injury and achieved a complete response. Conclusion Pembrolizumab has a high risk of inducing lung injury in patients with preexisting ILD, although it may be very effective in NSCLC patients with a high PD-L1 expression, even concurrent with preexisting ILD. Further large-scale studies are needed to determine risk factors of pembrolizumab-induced lung injury in such patients.

/ObjectivesThe aim of this study was to clarify the oncological outcomes of patients with intraductal papillary mucinous neoplasm (IPMN) who underwent limited resection (LR).This retrospective study analyzed the data of 110 patients with IPMN. Patients with IPMN without a history of pancreatitis who had neither tumor infiltration nor regional lymph node swelling on imaging findings underwent LR. We assessed the oncological outcomes of LR for patients with IPMN by comparing the surgical outcomes of LR and standard resection.LR was performed in 50 patients (45.5%), including duodenum-preserving pancreatic head resection (n = 31), middle-pancreatectomy (n = 12), spleen-preserving distal pancreatectomy (n = 3), total parenchymal pancreatectomy (n = 3), and partial resection (n = 1). In the LR group, 18 patients had postoperative complications of Clavien-Dindo classification ≥ IIIa. After histopathological examination, the presence of high-grade dysplasia (HGD) and invasive carcinoma (IC) were observed in nine and three patients, respectively, in the LR group, and eight and 22 patients, respectively, in the standard resection group. There was a significant difference in the histopathological diagnosis of IC between the two groups (p0.001). Finally, in the LR group, postoperative recurrences occurred in three patients, and the 5-, 10-, and 15-year disease-specific survival rates were all 97.0%.For patients with IPMN judged to have no infiltrating lesions based on the detailed imaging examination, LR is acceptable and may be considered as an alternative to standard resection.

BACKGROUND/PURPOSE Grade C postoperative pancreatic fistula (POPF), as defined by International Study Group of Pancreatic Fistula (ISGPF), is the most life-threatening complication after pancreatoduodenectomy (PD). This study aims to evaluate risk factors for Grade C POPF after PD. METHODS This is a prospective, multicenter study based in Japan and Taiwan. Between December 2014 and May 2017, 3022 patients were enrolled in this study and 2762 patients were analyzed. We analyzed risk factors of Grade C POPF based on the updated 2016 ISGPF scheme (organ failure, reoperation, and/or death). RESULTS Among 2762 patients, 46 patients (1.7%) developed Grade C POPF after PD. The mortality rate of the 46 patients with Grade C POPF was 37.0%. On the multivariate analysis, six independent risk factors for Grade C POPF were found; BMI ≥ 25.0 kg/m2 , chronic steroid use, preoperative serum albumin

This study sought to assess the disparity between regions and facilities in surgical resident training in Japan via a national level needs-assessment. A survey was sent to all 909 graduating residents of 2016. Residents trained in the six prefectures with a population of 7 million or more were included in the large prefecture (LP) group. Residents trained in the other 41 prefectures were included in the small prefecture (SP) group. Each group was further divided into a university hospital (UH) group and a non-university hospital (NUH) group. The response rate was 56.3% (n = 512). Excluding nine residents who did not report their prefectures and facilities, surveys from 503 residents were analyzed. The UH group received significantly more years of training. In the SP and UH groups, there were significantly fewer residents who had performed 150 procedures or more under general anesthesia in comparison to the LP and NUH groups, respectively. Self-assessed competencies for several procedures were significantly lower in the SP and UH groups. Disparity in surgical resident training was found between regions and facilities in Japan. The surgical residency curriculum in Japan could be improved to address this problem.

Background: Total pancreatectomy (TP) used to be applied for pancreatic cancer to obtain better oncological clearance or to avoid pancreatic fistulae, but indications have changed. The aim of this study was to clarify recent disease indications and outcomes for this procedure. Methods: A total of 26 patients who underwent one-stage surgery (n=11) or two-stage surgery (n=15) were analyzed retrospectively. Results: The postoperative morbidity rate was 26.9%, but no postoperative mortality was encountered. Twenty-two patients had multiple diseases, including intraductal papillary mucinous neoplasm (IPMN) -associated tumors in 12 and de novo pancreatic ductal carcinoma (PDAC) in 5. Significantly more T3/T4 and stage III/IV tumors were included in the de novo PDAC group than in the IPMN-associated tumor group (T3/T4: 70% vs. 16.7%, p=0.002; stage III/IV: 100% vs. 33.3%, p=0.012). Two-year survival rates were lower in the de novo PDAC group (20%) than in the IPMN-associated tumor group (68.8%, p=0.041). Conclusions: TP can be performed safely with low mortality and acceptable morbidity. Our study revealed that the most frequent indication for TP was multiple diseases, and the two main cohorts involved different malignancies: IPMN-associated tumors; and de novo PDAC.

Introduction Gait exercise assist robot (GEAR), a gait rehabilitation robot developed for poststroke gait disorder, has been shown to improve walking speed and to improve the poststroke gait pattern. However, the persistence of its beneficial effect has not been clarified. In this matched case-control study, we assessed the durability of the effectiveness of GEAR training in patients with subacute stroke on the basis of clinical evaluation and three-dimensional (3D) gait analysis. Methods Gait data of 10 patients who underwent GEAR intervention program and 10 patients matched for age, height, sex, affected side, type of stroke, and initial gait ability who underwent conventional therapy were extracted from database. The outcome measures were walk score of Functional Independence Measure (FIM-walk), Stroke Impairment Assessment Set total lower limb motor function score (SIAS-L/E), and 3D gait analysis data (spatiotemporal factors and abnormal gait patter indices) at three time points: baseline, at the end of intervention, and within 1 week before discharge. Results In the GEAR group, the FIM-walk score, SIAS-L/E score, cadence, and single stance time of paretic side at discharge were significantly higher than those at post-training (p < 0.05), whereas the stance time and double support time of the unaffected side, knee extensor thrust, insufficient knee flexion, and external rotated hip of the affected side were significantly lower (p < 005). However, no significant differences in these respects were observed in the control group between the corresponding evaluation time points. Conclusion The results indicated significant improvement in the GEAR group after the training period, with respect to both clinical parameters and the gait pattern indices. This improvement was not evident in the control group after the training period. The results possibly support the effectiveness of GEAR training in conferring persistently efficient gait patterns in patients with poststroke gait disorder. Further studies should investigate the long-term effects of GEAR training in a larger sample.

Background Intraperitoneal chemotherapy using paclitaxel is considered an experimental approach for treating peritoneal carcinomatosis. This study aimed to determine the recommended dose, and to evaluate the clinical efficacy and safety, of the combination of intravenous gemcitabine, intravenous nab‐paclitaxel and intraperitoneal paclitaxel in patients with pancreatic cancer and peritoneal metastasis. Methods The frequencies of dose‐limiting toxicities were evaluated, and the recommended dose was determined in phase I. The primary endpoint of the phase II analysis was overall survival rate at 1 year. Secondary endpoints were antitumour effects, symptom‐relieving effects, safety and overall survival. Results The recommended doses of intravenous gemcitabine, intravenous nab‐paclitaxel and intraperitoneal paclitaxel were 800, 75 and 20 mg/m2 respectively. Among 46 patients enrolled in phase II, the median time to treatment failure was 6·0 (range 0–22·6) months. The response and disease control rates were 21 of 43 and 41 of 43 respectively. Ascites disappeared in 12 of 30 patients, and cytology became negative in 18 of 46. The median survival time was 14·5 months, and the 1‐year overall survival rate was 61 per cent. Conversion surgery was performed in eight of 46 patients, and those who underwent resection survived significantly longer than those who were not treated surgically (median survival not reached versus 12·4 months). Grade 3–4 haematological toxicities developed in 35 of 46 patients, whereas non‐haematological adverse events occurred in seven patients. Conclusion Adding intraperitoneal paclitaxel had clinical efficacy with acceptable tolerability., This multicentre phase I/II study was undertaken to determine the recommended dose of the combination of intravenous gemcitabine, intravenous nab‐paclitaxel and intraperitoneal paclitaxel in patients with pancreatic ductal adenocarcinoma and peritoneal metastasis, and to evaluate its clinical efficacy and safety. This regimen exhibited promising clinical efficacy, with acceptable tolerability. Effective and safe in pancreatic cancer

Postoperative pancreatic fistula is a main cause of fatal complications post-pancreatoduodenectomy. However, no universally accepted drainage management exists for clinically relevant postoperative pancreatic fistulas. We retrospectively evaluated cases in which drain contrast imaging was used to determine its utility in identifying clinically relevant postoperative pancreatic fistulas post-pancreatoduodenectomy. Between January 2014 and December 2018, 209 consecutive patients who underwent pancreatoduodenectomy in our institute were retrospectively analyzed. Drain monitoring with contrast imaging was performed in 47 of the cases. We classified drain contrast type into three categories and evaluated postoperative outcome in each group: (1) fistulous tract group—only the fistula was contrasted; (2) fluid collection group – fluid collection connected to the drain fistula; and (3) pancreatico-anastomotic fistula group—fistula connected to the digestive tract. The durations of postoperative hospital stay and drainage were significantly shorter in the fistulous tract group than in the fluid collection group (31 vs. 46 days, p = 0.0026; and 12 vs. 38 days, p

Background: Histopathological findings would impact the timing of early cholecystectomy, but no reports have yet discussed. The aim of this study is to examine the feasible timing for early cholecystectomy based on both conventional clinicopathological data and histopathological findings. Methods: We retrospectively analyzed 127 patients who underwent laparoscopic cholecystectomy for acute cholecystitis (AC) at in our institutes between 2010 and 2015. Patients were categorized into two groups according to the interval between surgery and symptom onset (early, £96 h; delayed, >96 h) for comparison of clinical results. In addition, both histopathological findings and clinical results were compared between the early group (£96 h) and a sub-delayed subgroup of patients who underwent cholecystectomy at >96 h but ≦240 h. Results: No significant differences in surgical results were seen between the early group and delayed group. In terms of histopathological findings, the sub-delayed subgroup showed significant phase progression of cholecystitis compared to the early group. However, edema in the gallbladder (GB) wall was comparable in all cases operated on within 240 h, mirroring the lack of significant differences in surgical results seen between early and sub-delayed subgroups. Conclusion: Edema in the GB wall with AC is continuous within 10 days from onset, and emergency laparoscopic cholecystectomy within this period is safe and feasible.

BACKGROUND Lymph node metastasis is an important prognostic factor for distal bile duct cancer. The number of lymph node metastases was adopted for nodal classification. However, different cutoff values have been proposed, ranging from two to five. METHODS A total of 1748 cases who underwent curative surgery with pancreatoduodenectomy for distal bile duct cancer registered in the nationwide biliary tract cancer registry in Japan from 2008 to 2013 were included. Univariate Cox regression was performed to assess the effect of prognostic lymph node metastasis counts on mortality and to determine cutoff values. RESULTS The overall survival rate after resection was 47.4% at 5 years. Univariate and multivariate analysis found prognostic factors to include lymph node metastasis. The cutoff point was set to two lymph node metastases using the Cox model. There were significant differences in pairwise comparisons between three groups by the number of metastatic lymph node (P

Background Rectal neuroendocrine neoplasms (NENs) are rare, but their incidence has increased in recent years. The metastasis rate is low in cases of a tumor diameter Case presentation Here, we report three cases of metachronous liver metastasis after long-term follow-up of endoscopic mucosal resection (EMR) for rectal NEN. The pathological findings indicated a depth lower than the submucosa and complete radical resection in all cases and lymphovascular invasion in only one case. All three cases showed metachronous multiple liver metastases after 9–13 years of follow-up for EMR, despite achieving complete resection and without muscular invasion. Conclusions Metachronous liver metastases may occur after long interval following endoscopic resection; thus, long-term follow-up is necessary after endoscopic resection for rectal NEN.

Background The association between delayed gastric emptying (DGE) after pancreatoduodenectomy (PD) and pancreatic reconstruction technique remain unclear. The aim of this study is to investigate whether the occurrence of DGE differs between pancreaticojejunostomy (PJ) and pancreaticogastrostomy (PG). Methods A total of 83 patients who underwent subtotal stomach-preserving pancreatoduodenectomy was retrospectively analyzed, and the factors associated with clinically relevant DGE were explored. These patients were divided into a PG group and a PJ group according to the pancreatic reconstruction. DGE occurrence and its association with intra-abdominal complications was compared between the two types of pancreatic reconstruction. Results The overall incidence of DGE was 27.7%. Intra-abdominal complications including pancreatic fistula were strongly associated with DGE. As to the pancreatic reconstruction, DGE developed more frequently in the PG than in the PJ. In addition, DGE with intra-abdominal complications tended to be more frequent in PG, despite the fact that intra-abdominal complications occurred at a similar frequency in both groups. Conclusions Intra-abdominal complications were strongly associated with DGE. As to the pancreatic reconstruction, DGE developed more frequently in the PG than in the PJ. We speculate that intra-abdominal complications affected patients with PG more and resulted in frequent occurrence of DGE.

Most models for predicting malignant pancreatic intraductal papillary mucinous neoplasms were developed based on logistic regression (LR) analysis. Our study aimed to develop risk prediction models using machine learning (ML) and LR techniques and compare their performances. This was a multinational, multi-institutional, retrospective study. Clinical variables including age, sex, main duct diameter, cyst size, mural nodule, and tumour location were factors considered for model development (MD). After the division into a MD set and a test set (2:1), the best ML and LR models were developed by training with the MD set using a tenfold cross validation. The test area under the receiver operating curves (AUCs) of the two models were calculated using an independent test set. A total of 3,708 patients were included. The stacked ensemble algorithm in the ML model and variable combinations containing all variables in the LR model were the most chosen during 200 repetitions. After 200 repetitions, the mean AUCs of the ML and LR models were comparable (0.725 vs. 0.725). The performances of the ML and LR models were comparable. The LR model was more practical than ML counterpart, because of its convenience in clinical use and simple interpretability.

MC3 Working Group: Rehan Akbani21, Pavana Anur22, Matthew H. Bailey1,2,3, Alex Buchanan9, Kami Chiotti9, Kyle Covington12,23, Allison Creason9, Li Ding1,2,3,20, Kyle Ellrott9, Yu Fan21, Steven Foltz1,2, Gad Getz8,14,15,16, Walker Hale12, David Haussler24,25, Julian M. Hess8,26, Carolyn M. Hutter27, Cyriac Kandoth28, Katayoon Kasaian29,30, Melpomeni Kasapi27, Dave Larson1 , Ignaty Leshchiner8, John Letaw31, Singer Ma32, Michael D. McLellan1,3,20, Yifei Men32, Gordon B. Mills33,34, Beifang Niu35, Myron Peto22, Amie Radenbaugh24, Sheila M. Reynolds36, Gordon Saksena8, Heidi Sofia27, Chip Stewart8, Adam J. Struck31, Joshua M. Stuart24,37, Wenyi Wang21, John N. Weinstein38, David A. Wheeler12,13, Christopher K. Wong24,39, Liu Xi12 & Kai Ye40,41 21Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. 22Molecular and Medical Genetics, OHSU Knight Cancer Institute, Oregon Health and Science University, Portland, OR 97239, USA. 23Castle Biosciences Inc, Friendswood, TX 77546, USA. 24UC Santa Cruz Genomics Institute, University of California Santa Cruz, Santa Cruz, CA 95064, USA. 25Howard Hughes Medical Institute, University of California Santa Cruz, Santa Cruz, CA 95064, USA. 26Massachusetts General Hospital Center for Cancer Research, Charlestown, MA 02114, USA. 27National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20894, USA. 28Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. 29Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada. 30Canada’s Michael Smith Genome Sciences Centre, BC Cancer, Vancouver, BC V5Z 4S6, Canada. 31Computational Biology Program, School of Medicine, Oregon Health and Science University, Portland, OR 97239, USA. 32DNAnexus Inc, Mountain View, CA 94040, USA. 33Department of Systems Biology, UT MD Anderson Cancer Center, Houston, TX 77030, USA. 34Precision Oncology, OHSU Knight Cancer Institute, Oregon Health and Science University, Portland, OR 97239, USA. 35Computer Network Information Center, Chinese Academy of Sciences, Beijing, China. 36Institute for Systems Biology, Seattle, WA 98109, USA. 37Department of Biomolecular Engineering, University of California Santa Cruz, Santa Cruz, CA 95064, USA. 38Department of Bioinformatics and Computational Biology and Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. 39Biomolecular Engineering Department, University of California Santa Cruz, Santa Cruz, CA 95064, USA. 40School of Elect, PCAWG novel somatic mutation calling methods working group: Matthew H. Bailey1,2,3, Beifang Niu35, Matthias Bieg42,43, Paul C. Boutros6,44,45,46, Ivo Buchhalter43,47,48, Adam P. Butler49, Ken Chen50, Zechen Chong51, Li Ding1,2,3,20, Oliver Drechsel52,53, Lewis Jonathan Dursi6,7, Roland Eils47,48,54,55, Kyle Ellrott9, Shadrielle M. G. Espiritu6, Yu Fan21, Robert S. Fulton1,3,20, Shengjie Gao56, Josep L. l. Gelpi57,58, Mark B. Gerstein5,18,19, Gad Getz8,14,15,16, Santiago Gonzalez59,60, Ivo G. Gut52,61, Faraz Hach62,63, Michael C. Heinold47,48, Julian M. Hess8,26, Jonathan Hinton49, Taobo Hu64, Vincent Huang6, Yi Huang65,66, Barbara Hutter43,67,68, David R. Jones49, Jongsun Jung69, Natalie Jäger47, Hyung-Lae Kim70, Kortine Kleinheinz47,48, Sushant Kumar5,19, Yogesh Kumar64, Christopher M. Lalansingh6, Ignaty Leshchiner8, Ivica Letunic71, Dimitri Livitz8, Eric Z. Ma64, Yosef E. Maruvka8,26,72, R. Jay Mashl1,2, Michael D. McLellan1,3,20, Andrew Menzies49, Ana Milovanovic57, Morten Muhlig Nielsen73, Stephan Ossowski52,53,74, Nagarajan Paramasivam43,47, Jakob Skou Pedersen73,75, Marc D. Perry76,77, Montserrat Puiggròs57, Keiran M. Raine49, Esther Rheinbay8,14,72, Romina Royo57, S. Cenk Sahinalp62,78,79, Gordon Saksena8, Iman Sarrafi62,78, Matthias Schlesner47,80, Jared T. Simpson6,17, Lucy Stebbings49, Chip Stewart8, Miranda D. Stobbe52,61, Jon W. Teague49, Grace Tiao8, David Torrents57,81, Jeremiah A. Wala8,14,82, Jiayin Wang1,40,66, Wenyi Wang21, Sebastian M. Waszak60, Joachim Weischenfeldt60,83,84, Michael C. Wendl1,10,11, Johannes Werner47,85, Zhenggang Wu64, Hong Xue64, Sergei Yakneen60, Takafumi N. Yamaguchi6, Kai Ye40,41, Venkata D. Yellapantula20,86, Christina K. Yung76 & Junjun Zhang76, PCAWG Consortium: Lauri A. Aaltonen87, Federico Abascal49, Adam Abeshouse88, Hiroyuki Aburatani89, David J. Adams49, Nishant Agrawal90, Keun Soo Ahn91, Sung-Min Ahn92, Hiroshi Aikata93, Rehan Akbani21, Kadir C. Akdemir50, Hikmat Al-Ahmadie88, Sultan T. Al-Sedairy94, Fatima Al-Shahrour95, Malik Alawi96,97, Monique Albert98, Kenneth Aldape99,100, Ludmil B. Alexandrov49,101,102, Adrian Ally30, Kathryn Alsop103, Eva G. Alvarez104,105,106, Fernanda Amary107, Samirkumar B. Amin108,109,110, Brice Aminou76, Ole Ammerpohl111,112, Matthew J. Anderson113, Yeng Ang114, Davide Antonello115, Pavana Anur22, Samuel Aparicio116, Elizabeth L. Appelbaum1,117, Yasuhito Arai118, Axel Aretz119, Koji Arihiro93, Shun-ichi Ariizumi120, Joshua Armenia121, Laurent Arnould122, Sylvia Asa123,124, Yassen Assenov125, Gurnit Atwal6,126,127, Sietse Aukema112,128, J. Todd Auman129, Miriam R. Aure130, Philip Awadalla6,126, Marta Aymerich131, Gary D. Bader126, Adrian Baez-Ortega132, Matthew H. Bailey1,2,3, Peter J. Bailey133, Miruna Balasundaram30, Saianand Balu134, Pratiti Bandopadhayay8,135,136, Rosamonde E. Banks137, Stefano Barbi138, Andrew P. Barbour139,140, Jonathan Barenboim6, Jill Barnholtz-Sloan141,142, Hugh Barr143, Elisabet Barrera59, John Bartlett98,144, Javier Bartolome57, Claudio Bassi115, Oliver F. Bathe145,146, Daniel Baumhoer147, Prashant Bavi148, Stephen B. Baylin149,150, Wojciech Bazant59, Duncan Beardsmore151, Timothy A. Beck152,153, Sam Behjati49, Andreas Behren154, Beifang Niu35, Cindy Bell155, Sergi Beltran52,61, Christopher Benz156, Andrew Berchuck157, Anke K. Bergmann158, Erik N. Bergstrom101,102, Benjamin P. Berman159,160,161, Daniel M. Berney162, Stephan H. Bernhart163,164,165, Rameen Beroukhim8,14,82, Mario Berrios166, Samantha Bersani167, Johanna Bertl73,168, Miguel Betancourt169, Vinayak Bhandari6,44, Shriram G. Bhosle49, Andrew V. Biankin133,170,171,172, Matthias Bieg42,43, Darell Bigner173, Hans Binder163,164, Ewan Birney59, Michael Birrer72, Nidhan K. Biswas174, Bodil Bjerkehagen147,175, Tom Bodenheimer134, Lori Boice176, Giada Bonizzato177, Johann S. De Bono178, Arnoud Boot179,180, Moiz S. Bootwalla166, Ake Borg181, Arndt Borkhardt182, Keith A. Boroevich183,184, Ivan Borozan6, Christoph Borst185, Marcus Bosenberg186, Mattia Bosio52,53,57, Jacqueline Boultwood187, Guillaume Bourque188,189, Paul C. Boutros6,44,45,46, G. Steven Bova190, David T. Bowen49,191, Reanne Bowlby30, David D. L. Bowtell103, Sandrine Boyault192, Rich Boyce59, Jeffrey Boyd193, Alvis Brazma59, Paul Brennan194, Daniel S. Brewer195,196, Arie B. Brinkman197, Robert G. Bristow44,198,199,200,201, Russell R. Broaddus99, Jane E. Brock202, Malcolm Brock203, Annegien Broeks204, Angela N. Brooks8,24,37,82, Denise Brooks30, Benedikt Brors67,205,206, Søren Brunak207,208, Timothy J. C. Bruxner113,209, Alicia L. Bruzos104,105,106, Alex Buchanan9, Ivo Buchhalter43,47,48, Christiane Buchholz210, Susan Bullman8,82, Hazel Burke211, Birgit Burkhardt212, Kathleen H. Burns213,214, John Busanovich8,215, Carlos D. Bustamante216,217, Adam P. Butler49, Atul J. Butte218, Niall J. Byrne76, Anne-Lise Børresen-Dale130,219, Samantha J. Caesar-Johnson220, Andy Cafferkey59, Declan Cahill221, Claudia Calabrese59,60, Carlos Caldas222,223, Fabien Calvo224, Niedzica Camacho178, Peter J. Campbell49,225, Elias Campo226,227, Cinzia Cantù177, Shaolong Cao21, Thomas E. Carey228, Joana Carlevaro-Fita229,230,231, Rebecca Carlsen30, Ivana Cataldo167,177, Mario Cazzola232, Jonathan Cebon154, Robert Cerfolio233, Dianne E. Chadwick234, Dimple Chakravarty235, Don Chalmers236, Calvin Wing Yiu Chan47,237, Kin Chan238, Michelle Chan-Seng-Yue148, Vishal S. Chandan239, David K. Chang133,170, Stephen J. Chanock240, Lorraine A. Chantrill170,241, Aurélien Chateigner76,242, Nilanjan Chatterjee149,243, Kazuaki Chayama93, Hsiao-Wei Chen114,121, Jieming Chen218, Ken Chen50, Yiwen Chen21, Zhaohong Chen244, Andrew D. Cherniack8,82, Jeremy Chien245, Yoke-Eng Chiew246,247, Suet-Feung Chin222,223, Juok Cho8, Sunghoon Cho248, Jung Kyoon Choi249, Wan Choi250, Christine Chomienne251, Zechen Chong51, Su Pin Choo252, Angela Chou170,246, Angelika N. Christ113, Elizabeth L. Christie103, Eric Chuah30, Carrie Cibulskis8, Kristian Cibulskis8, Sara Cingarlini253, Peter Clapham49, Alexander Claviez254, Sean Cleary148,255, Nicole Cloonan256, Marek Cmero257,258,259, Colin C. Collins62, Ashton A. Connor255,260, Susanna L. Cooke133, Colin S. Cooper178,196,261, Leslie Cope149, Vincenzo Corbo138,177, Matthew G. Cordes1,262, Stephen M. Cordner263, Isidro Cortés-Ciriano264,265,266, Kyle Covington12,23, Prue A. Cowin267, Brian Craft24, David Craft8,268, Chad J. Creighton269, Yupeng Cun270, Erin Curley271, Ioana Cutcutache179,180, Karolina Czajka272, Bogdan Czerniak99,273, Rebecca A. Dagg274, Ludmila Danilova149, Maria Vittoria Davi275, Natalie R. Davidson276,277,278,279,280, Helen Davies49,281,282, Ian J. Davis283, Brandi N. Davis-Dusenbery284, Kevin J. Dawson49, Francisco M. De La Vega216,217,285, Ricardo De Paoli-Iseppi211, Timothy Defreitas8, Angelo P. Dei Tos286, Olivier Delaneau287,288,289, John A. Demchok220, Jonas Demeulemeester290,291, German M. Demidov52,53,74, Deniz Demircioğlu292,293, Nening M. Dennis221, Robert E. Denroche148, Stefan C. Dentro49,290,294, Nikita Desai76, Vikram Deshpande72, Amit G. Deshwar295, Christine Desmedt296,297, Jordi Deu-Pons298,299, Noreen Dhalla30, Neesha C. Dhani300, Priyanka Dhingra301,302, Rajiv Dhir303, Anthony DiBiase304, Klev Diamanti305, Li Ding1,2,3,20, Shuai Ding306, Huy Q. Dinh159, Luc Dirix307, HarshaVardhan Doddapaneni12, Nilgun Donmez62,78, Michelle T. Dow244, Ronny Drapkin308, Oliver Drechsel52,53, Ruben M. Drews223, Serge Serge49, Tim Dudderidge150,221, Ana Dueso-Barroso57, Andrew J. Dunford8, Michael Dunn309, Lewis Jonathan Dursi6,7, Fraser R. Duthie133,310, Ken Dutton-Regester311, Jenna Eagles272, Douglas F. Easton312,313, Stuart Edmonds314, Paul A. Edwards223,315, Sandra E. Edwards178, Rosalind A. Eeles178,221, Anna Ehinger316, Juergen Eils54,55, Roland Eils47,48,54,55, Adel El-Naggar99,273, Matthew Eldridge223, Kyle Ellrott9, Serap Erkek60, Georgia Escaramis53,317,318, Shadrielle M. G. Espiritu6, Xavier Estivill53,319, Dariush Etemadmoghadam103, Jorunn E. Eyfjord320, Bishoy M. Faltas280, Daiming Fan321, Yu Fan21, William C. Faquin72, Claudiu Farcas244, Matteo Fassan322, Aquila Fatima323, Francesco Favero324, Nodirjon Fayzullaev76, Ina Felau220, Sian Fereday103, Martin L. Ferguson325, Vincent Ferretti76,326, Lars Feuerbach205, Matthew A. Field327, J. Lynn Fink57,113, Gaetano Finocchiaro328, Cyril Fisher221, Matthew W. Fittall290, Anna Fitzgerald329, Rebecca C. Fitzgerald282, Adrienne M. Flanagan330, Neil E. Fleshner331, Paul Flicek59, John A. Foekens332, Kwun M. Fong333, Nuno A. Fonseca59,334, Christopher S. Foster335,336, Natalie S. Fox6, Michael Fraser6, Scott Frazer8, Milana Frenkel-Morgenstern337, William Friedman338, Joan Frigola298, Catrina C. Fronick1,262, Akihiro Fujimoto184, Masashi Fujita184, Masashi Fukayama339, Lucinda A. Fulton1 , Robert S. Fulton1,3,20, Mayuko Furuta184, P. Andrew Futreal340, Anja Füllgrabe59, Stacey B. Gabriel8, Steven Gallinger148,255,260, Carlo Gambacorti-Passerini341, Jianjiong Gao121, Shengjie Gao56, Levi Garraway82, Øystein Garred342, Erik Garrison49, Dale W. Garsed103, Nils Gehlenborg8,343, Josep L. l. Gelpi57,58, Joshy George110, Daniela S. Gerhard344, Clarissa Gerhauser345, Jeffrey E. Gershenwald346,347, Mark B. Gerstein5,18,19, Moritz Gerstung59,60, Gad Getz8,14,15,16, Mohammed Ghori49, Ronald Ghossein348, Nasra H. Giama349, Richard A. Gibbs12, Anthony J. Gill170,350, Pelvender Gill351, Dilip D. Giri348, Dominik Glodzik49, Vincent J. Gnanapragasam352,353, Maria Elisabeth Goebler354, Mary J. Goldman24, Carmen Gomez355, Santiago Gonzalez59,60, Abel Gonzalez-Perez298,299,356, Dmitry A. Gordenin357, James Gossage358, Kunihito Gotoh359, Ramaswamy Govindan3, Dorthe Grabau360, Janet S. Graham133,361, Robert C. Grant148,260, Anthony R. Green315, Eric Green27, Liliana Greger59, Nicola Grehan282, Sonia Grimaldi177, Sean M. Grimmond362, Robert L. Grossman363, Adam Grundhoff97,364, Gunes Gundem88, Qianyun Guo75, Manaswi Gupta8, Shailja Gupta365, Ivo G. Gut52,61, Marta Gut52,61, Jonathan Göke292,366, Gavin Ha8, Andrea Haake111, David Haan37, Siegfried Haas185, Kerstin Haase290, James E. Haber367, Nina Habermann60, Faraz Hach62,63, Syed Haider6, Natsuko Hama118, Freddie C. Hamdy351, Anne Hamilton267, Mark P. Hamilton368, Leng Han369, George B. Hanna370, Martin Hansmann371, Nicholas J. Haradhvala8,72, Olivier Harismendy102,372, Ivon Harliwong113, Arif O. Harmanci5,373, Eoghan Harrington374, Takanori Hasegawa375, David Haussler24,25, Steve Hawkins223, Shinya Hayami376, Shuto Hayashi375, D. Neil Hayes134,377,378, Stephen J. Hayes379,380, Nicholas K. Hayward211,311, Steven Hazell221, Yao He381, Allison P. Heath382, Simon C. Heath52,61, David Hedley300, Apurva M. Hegde38, David I. Heiman8, Michael C. Heinold47,48, Zachary Heins88, Lawrence E. Heisler152, Eva Hellstrom-Lindberg383, Mohamed Helmy384, Seong Gu Heo385, Austin J. Hepperla134, José María Heredia-Genestar386, Carl Herrmann47,48,387, Peter Hersey211, Julian M. Hess8,26, Holmfridur Hilmarsdottir320, Jonathan Hinton49, Satoshi Hirano388, Nobuyoshi Hiraoka389, Katherine A. Hoadley134,390, Asger Hobolth75,168, Ermin Hodzic78, Jessica I. Hoell182, Steve Hoffmann163,164,165,391, Oliver Hofmann392, Andrea Holbrook166, Aliaksei Z. Holik53, Michael A. Hollingsworth393, Oliver Holmes209,311, Robert A. Holt30, Chen Hong205,237, Eun Pyo Hong385, Jongwhi H. Hong394, Gerrit K. Hooijer395, Henrik Hornshøj73, Fumie Hosoda118, Yong Hou56,396, Volker Hovestadt397, William Howat352, Alan P. Hoyle134, Ralph H. Hruban149, Jianhong Hu12, Taobo Hu64, Xing Hua240, Kuan-lin Huang1,398, Mei Huang176, Mi Ni Huang179,180, Vincent Huang6, Yi Huang65,66, Wolfgang Huber60, Thomas J. Hudson272,399, Michael Hummel400, Jillian A. Hung246,247, David Huntsman401, Ted R. Hupp402, Jason Huse88, Matthew R. Huska403, Barbara Hutter43,67,68, Carolyn M. Hutter27, Daniel Hübschmann48,54,404,405,406, Christine A. Iacobuzio-Donahue348, Charles David Imbusch205, Marcin Imielinski407,408, Seiya Imoto375, William B. Isaacs409, Keren Isaev6,44, Shumpei Ishikawa410, Murat Iskar397, S. M. Ashiqul Islam244, Michael Ittmann411,412,413, Sinisa Ivkovic284, Jose M. G. Izarzugaza414, Jocelyne Jacquemier415, Valerie Jakrot211, Nigel B. Jamieson133,172,416, Gun Ho Jang148, Se Jin Jang417, Joy C. Jayaseelan12, Reyka Jayasinghe1 , Stuart R. Jefferys134, Karine Jegalian418, Jennifer L. Jennings419, Seung-Hyup Jeon250, Lara Jerman60,420, Yuan Ji421,422, Wei Jiao6, Peter A. Johansson311, Amber L. Johns170, Jeremy Johns272, Rory Johnson230,423, Todd A. Johnson183, Clemency Jolly290, Yann Joly424, Jon G. Jonasson320, Corbin D. Jones425, David R. Jones49, David T. W. Jones426,427, Nic Jones428, Steven J. M. Jones30, Jos Jonkers204, Young Seok Ju49,249, Hartmut Juhl429, Jongsun Jung69, Malene Juul73, Randi Istrup Juul73, Sissel Juul374, Natalie Jäger47, Rolf Kabbe47, Andre Kahles276,277,278,279,430, Abdullah Kahraman431,432,433, Vera B. Kaiser434, Hojabr Kakavand211, Sangeetha Kalimuthu148, Christof von Kalle405, Koo Jeong Kang91, Katalin Karaszi351, Beth Karlan435, Rosa Karlić436, Dennis Karsch437, Katayoon Kasaian29,30, Karin S. Kassahn113,438, Hitoshi Katai439, Mamoru Kato440, Hiroto Katoh410, Yoshiiku Kawakami93, Jonathan D. Kay117, Stephen H. Kazakoff209,311, Marat D. Kazanov441,442,443, Maria Keays59, Electron Kebebew444,445, Richard F. Kefford446, Manolis Kellis8,447, James G. Kench170,350,448, Catherine J. Kennedy246,247, Jules N. A. Kerssemakers47, David Khoo273, Vincent Khoo221, Narong Khuntikeo115,449, Ekta Khurana301,302,450,451, Helena Kilpinen117, Hark Kyun Kim452, Hyung-Lae Kim70, Hyung-Yong Kim415, Hyunghwan Kim250, Jaegil Kim8, Jihoon Kim453, Jong K. Kim454, Youngwook Kim455,456, Tari A. King457,458,459, Wolfram Klapper128, Kortine Kleinheinz47,48, Leszek J. Klimczak460, Stian Knappskog49,461, Michael Kneba437, Bartha M. Knoppers424, Youngil Koh462,463, Jan Komorowski305,464, Daisuke Komura410, Mitsuhiro Komura375, Gu Kong415, Marcel Kool426,465, Jan O. Korbel59,60, Viktoriya Korchina12, Andrey Korshunov465, Michael Koscher465, Roelof Koster466, Zsofia Kote-Jarai178, Antonios Koures244, Milena Kovacevic284, Barbara Kremeyer49, Helene Kretzmer164,165, Markus Kreuz467, Savitri Krishnamurthy99,468, Dieter Kube469, Kiran Kumar8, Pardeep Kumar221, Sushant Kumar5,19, Yogesh Kumar64, Ritika Kundra114,121, Kirsten Kübler8,14,72, Ralf Küppers470, Jesper Lagergren383,471, Phillip H. Lai166, Peter W. Laird472, Sunil R. Lakhani473, Christopher M. Lalansingh6, Emilie Lalonde6, Fabien C. Lamaze6, Adam Lambert351, Eric Lander8, Pablo Landgraf474,475, Luca Landoni115, Anita Langerød130, Andrés Lanzós230,231,423, Denis Larsimont476, Erik Larsson477, Mark Lathrop189, Loretta M. S. Lau478, Chris Lawerenz55, Rita T. Lawlor177, Michael S. Lawrence8,72,183, Alexander J. Lazar99,108, Xuan Le479, Darlene Lee30, Donghoon Lee5, Eunjung Alice Lee480, Hee Jin Lee417, Jake June-Koo Lee264,266, Jeong-Yeon Lee481, Juhee Lee482, Ming Ta Michael Lee340, Henry Lee-Six49, Kjong-Van Lehmann276,277,278,279,430, Hans Lehrach483, Dido Lenze400, Conrad R. Leonard209,311, Daniel A. Leongamornlert49,178, Ignaty Leshchiner8, Louis Letourneau484, Ivica Letunic71, Douglas A. Levine88,485, Lora Lewis12, Tim Ley486, Chang Li56,396, Constance H. Li6,44, Haiyan Irene Li30, Jun Li21, Lin Li56, Shantao Li5, Siliang Li56,396, Xiaobo Li56,396, Xiaotong Li5, Xinyue Li56, Yilong Li49, Han Liang21, Sheng-Ben Liang234, Peter Lichter68,397, Pei Lin8, Ziao Lin8,487, W. M. Linehan488, Ole Christian Lingjærde489, Dongbing Liu56,396, Eric Minwei Liu88,301,302, Fei-Fei Liu201,490, Fenglin Liu381,491, Jia Liu492, Xingmin Liu56,396, Julie Livingstone6, Dimitri Livitz8, Naomi Livni221, Lucas Lochovsky5,19,110, Markus Loeffler467, Georgina V. Long211, Armando Lopez-Guillermo493, Shaoke Lou5,19, David N. Louis72, Laurence B. Lovat117, Yiling Lu38, Yong-Jie Lu162,494, Youyong Lu495,496,497, Claudio Luchini167, Ilinca Lungu144,148, Xuemei Luo152, Hayley J. Luxton117, Andy G. Lynch223,315,498, Lisa Lype36, Cristina López111,112, Carlos López-Otín499, Eric Z. Ma64, Yussanne Ma30, Gaetan MacGrogan500, Shona MacRae501, Geoff Macintyre223, Tobias Madsen73, Kazuhiro Maejima184, Andrea Mafficini177, Dennis T. Maglinte166,502, Arindam Maitra174, Partha P. Majumder174, Luca Malcovati232, Salem Malikic62,78, Giuseppe Malleo115, Graham J. Mann211,246,503, Luisa Mantovani-Löffler504, Kathleen Marchal505,506, Giovanni Marchegiani115, Elaine R. Mardis1,193,507, Adam A. Margolin31, Maximillian G. Marin37, Florian Markowetz223,315, Julia Markowski403, Jeffrey Marks508, Tomas Marques-Bonet61,81,386,509, Marco A. Marra30, Luke Marsden351, John W. M. Martens332, Sancha Martin49,510, Jose I. Martin-Subero81,511, Iñigo Martincorena49, Alexander Martinez-Fundichely301,302,451 Yosef E. Maruvka8,26,72, R. Jay Mashl1,2, Charlie E. Massie223, Thomas J. Matthew37, Lucy Matthews178, Erik Mayer221,512, Simon Mayes513, Michael Mayo30, Faridah Mbabaali272, Karen McCune514, Ultan McDermott49, Patrick D. McGillivray19, Michael D. McLellan1,3,20, John D. McPherson148,272,515, John R. McPherson179,180, Treasa A. McPherson260, Samuel R. Meier8, Alice Meng516, Shaowu Meng134, Andrew Menzies49, Neil D. Merrett115,517, Sue Merson178, Matthew Meyerson8,14,82, William U. Meyerson4,5, Piotr A. Mieczkowski518, George L. Mihaiescu76, Sanja Mijalkovic284, Ana Mijalkovic Mijalkovic-Lazic284, Tom Mikkelsen519, Michele Milella253, Linda Mileshkin103, Christopher A. Miller1 , David K. Miller113,170, Jessica K. Miller272, Gordon B. Mills33,34, Ana Milovanovic57, Sarah Minner520, Marco Miotto115, Gisela Mir Arnau267, Lisa Mirabello240, Chris Mitchell103, Thomas J. Mitchell49,315,352, Satoru Miyano375, Naoki Miyoshi375, Shinichi Mizuno521, Fruzsina Molnár-Gábor522, Malcolm J. Moore300, Richard A. Moore30, Sandro Morganella49, Quaid D. Morris127,490, Carl Morrison523,524, Lisle E. Mose134, Catherine D. Moser349, Ferran Muiños298,299, Loris Mularoni298,299, Andrew J. Mungall30, Karen Mungall30, Elizabeth A. Musgrove133, Ville Mustonen525,526,527, David Mutch528, Francesc Muyas52,53,74, Donna M. Muzny12, Alfonso Muñoz59, Jerome Myers529, Ola Myklebost461, Peter Möller530, Genta Nagae89, Adnan M. Nagrial170, Hardeep K. Nahal-Bose76, Hitoshi Nakagama531, Hidewaki Nakagawa184, Hiromi Nakamura118, Toru Nakamura388, Kaoru Nakano184, Tannistha Nandi532, Jyoti Nangalia49, Mia Nastic284, Arcadi Navarro61,81,386, Fabio C. P. Navarro19, David E. Neal223,352, Gerd Nettekoven533, Felicity Newell209,311, Steven J. Newhouse59, Yulia Newton37, Alvin Wei Tian Ng534, Anthony Ng535, Jonathan Nicholson49, David Nicol221, Yongzhan Nie321,536, G. Petur Nielsen72, Morten Muhlig Nielsen73, Serena Nik-Zainal49,281,282,537, Michael S. Noble8, Katia Nones209,311, Paul A. Northcott538, Faiyaz Notta148,539, Brian D. O’Connor76,540, Peter O’Donnell541, Maria O’Donovan282, Sarah O’Meara49, Brian Patrick O’Neill542, J. Robert O’Neill543, David Ocana59, Angelica Ochoa88, Layla Oesper544, Christopher Ogden221, Hideki Ohdan93, Kazuhiro Ohi375, Lucila Ohno-Machado244, Karin A. Oien523,545, Akinyemi I. Ojesina546,547,548, Hidenori Ojima549, Takuji Okusaka550, Larsson Omberg551, Choon Kiat Ong552, Stephan Ossowski52,53,74, German Ott553, B. F. Francis Ouellette76,554, Christine P’ng6, Marta Paczkowska6, Salvatore Paiella115, Chawalit Pairojkul523, Marina Pajic170, Qiang Pan-Hammarström56,555, Elli Papaemmanuil49, Irene Papatheodorou59, Nagarajan Paramasivam43,47, Ji Wan Park385, Joong-Won Park556, Keunchil Park557,558, Kiejung Park559, Peter J. Park264,266, Joel S. Parker518, Simon L. Parsons124, Harvey Pass560, Danielle Pasternack272, Alessandro Pastore276, Ann-Marie Patch209,311, Iris Pauporté251, Antonio Pea115, John V. Pearson209,311, Chandra Sekhar Pedamallu8,14,82, Jakob Skou Pedersen73,75, Paolo Pederzoli115, Martin Peifer270, Nathan A. Pennell561, Charles M. Perou129,518, Marc D. Perry76,77, Gloria M. Petersen562, Myron Peto22, Nicholas Petrelli563, Robert Petryszak59, Stefan M. Pfister426,465,564, Mark Phillips424, Oriol Pich298,299, Hilda A. Pickett478, Todd D. Pihl565, Nischalan Pillay566, Sarah Pinder567, Mark Pinese170, Andreia V. Pinho568, Esa Pitkänen60, Xavier Pivot569, Elena Piñeiro-Yáñez95, Laura Planko533, Christoph Plass345, Paz Polak8,14,15, Tirso Pons570, Irinel Popescu571, Olga Potapova572, Aparna Prasad52, Shaun R. Preston573, Manuel Prinz47, Antonia L. Pritchard311, Stephenie D. Prokopec6, Elena Provenzano574, Xose S. Puente499, Sonia Puig176, Montserrat Puiggròs57, Sergio Pulido-Tamayo505,506, Gulietta M. Pupo246, Colin A. Purdie575, Michael C. Quinn209,311, Raquel Rabionet52,53,576, Janet S. Rader577, Bernhard Radlwimmer397, Petar Radovic284, Benjamin Raeder60, Keiran M. Raine49, Manasa Ramakrishna49, Kamna Ramakrishnan49, Suresh Ramalingam578, Benjamin J. Raphael579, W. Kimryn Rathmell580, Tobias Rausch60, Guido Reifenberger475, Jüri Reimand6,44, Jorge Reis-Filho348, Victor Reuter348, Iker Reyes-Salazar298, Matthew A. Reyna579, Sheila M. Reynolds36, Esther Rheinbay8,14,72, Yasser Riazalhosseini189, Andrea L. Richardson323, Julia Richter111,128, Matthew Ringel581, Markus Ringnér181, Yasushi Rino582, Karsten Rippe405, Jeffrey Roach583, Lewis R. Roberts349, Nicola D. Roberts49, Steven A. Roberts584, A. Gordon Robertson30, Alan J. Robertson113, Javier Bartolomé Rodriguez57, Bernardo Rodriguez-Martin104,105,106, F. Germán Rodríguez-González83,332, Michael H. A. Roehrl44,123,148,234,585,586, Marius Rohde587, Hirofumi Rokutan440, Gilles Romieu588, Ilse Rooman170, Tom Roques262, Daniel Rosebrock8, Mara Rosenberg8,72, Philip C. Rosenstiel589, Andreas Rosenwald590, Edward W. Rowe221,591, Romina Royo57, Steven G. Rozen179,180,592, Yulia Rubanova17,127, Mark A. Rubin423,593,594,595,596, Carlota Rubio-Perez298,299,597, Vasilisa A. Rudneva60, Borislav C. Rusev177, Andrea Ruzzenente598, Gunnar Rätsch276,277,278,279,280,430, Radhakrishnan Sabarinathan298,299,599, Veronica Y. Sabelnykova6, Sara Sadeghi30, S. Cenk Sahinalp62,78,79, Natalie Saini357, Mihoko Saito-Adachi440, Gordon Saksena8, Adriana Salcedo6, Roberto Salgado600, Leonidas Salichos5,19, Richard Sallari8, Charles Saller601, Roberto Salvia115, Michelle Sam272, Jaswinder S. Samra115,602, Francisco Sanchez-Vega114,121, Chris Sander276,603,604, Grant Sanders134, Rajiv Sarin605, Iman Sarrafi62,78, Aya Sasaki-Oku184, Torill Sauer489, Guido Sauter520, Robyn P. M. Saw211, Maria Scardoni167, Christopher J. Scarlett170,606, Aldo Scarpa177, Ghislaine Scelo194, Dirk Schadendorf68,607, Jacqueline E. Schein30, Markus B. Schilhabel589, Matthias Schlesner47,80, Thorsten Schlomm84,608, Heather K. Schmidt1 , Sarah-Jane Schramm246, Stefan Schreiber609, Nikolaus Schultz121, Steven E. Schumacher8,323, Roland F. Schwarz59,403,405,610, Richard A. Scolyer211,448,602, David Scott428, Ralph Scully611, Raja Seethala612, Ayellet V. Segre8,613, Iris Selander260, Colin A. Semple434, Yasin Senbabaoglu276, Subhajit Sengupta614, Elisabetta Sereni115, Stefano Serra585, Dennis C. Sgroi72, Mark Shackleton103, Nimish C. Shah352, Sagedeh Shahabi234, Catherine A. Shang329, Ping Shang211, Ofer Shapira8,323, Troy Shelton271, Ciyue Shen603,604, Hui Shen615, Rebecca Shepherd49, Ruian Shi490, Yan Shi134, Yu-Jia Shiah6, Tatsuhiro Shibata118,616, Juliann Shih8,82, Eigo Shimizu375, Kiyo Shimizu617, Seung Jun Shin618, Yuichi Shiraishi375, Tal Shmaya285, Ilya Shmulevich36, Solomon I. Shorser6, Charles Short59, Raunak Shrestha62, Suyash S. Shringarpure217, Craig Shriver619, Shimin Shuai6,126, Nikos Sidiropoulos83, Reiner Siebert112,620, Anieta M. Sieuwerts332, Lina Sieverling205,237, Sabina Signoretti202,621, Katarzyna O. Sikora177, Michele Simbolo138, Ronald Simon520, Janae V. Simons134, Jared T. Simpson6,17, Peter T. Simpson473, Samuel Singer115,458, Nasa Sinnott-Armstrong8,217, Payal Sipahimalani30, Tara J. Skelly390, Marcel Smid332, Jaclyn Smith622, Karen Smith-McCune514, Nicholas D. Socci276, Heidi J. Sofia27, Matthew G. Soloway134, Lei Song240, Anil K. Sood623,624,625, Sharmila Sothi626, Christos Sotiriou244, Cameron M. Soulette37, Paul N. Span627, Paul T. Spellman22, Nicola Sperandio177, Andrew J. Spillane211, Oliver Spiro8, Jonathan Spring628, Johan Staaf181, Peter F. Stadler163,164,165, Peter Staib629, Stefan G. Stark277,279,618,630, Lucy Stebbings49, Ólafur Andri Stefánsson631, Oliver Stegle59,60,632, Lincoln D. Stein6,126, Alasdair Stenhouse633, Chip Stewart8, Stephan Stilgenbauer634, Miranda D. Stobbe52,61, Michael R. Stratton49, Jonathan R. Stretch211, Adam J. Struck31, Joshua M. Stuart24,37, Henk G. Stunnenberg396,635, Hong Su56,396, Xiaoping Su99, Ren X. Sun6, Stephanie Sungalee60, Hana Susak52,53, Akihiro Suzuki89,636, Fred Sweep637, Monika Szczepanowski128, Holger Sültmann67,638, Takashi Yugawa617, Angela Tam30, David Tamborero298,299, Benita Kiat Tee Tan639, Donghui Tan518, Patrick Tan180,532,592,640, Hiroko Tanaka375, Hirokazu Taniguchi616, Tomas J. Tanskanen641, Maxime Tarabichi49,290, Roy Tarnuzzer220, Patrick Tarpey642, Morgan L. Taschuk152, Kenji Tatsuno89, Simon Tavaré223,643, Darrin F. Taylor113, Amaro Taylor-Weiner8, Jon W. Teague49, Bin Tean Teh180,592,640,644,645, Varsha Tembe246, Javier Temes104,105, Kevin Thai76, Sarah P. Thayer393, Nina Thiessen30, Gilles Thomas646, Sarah Thomas221, Alan Thompson221, Alastair M. Thompson633, John F. Thompson211, R. Houston Thompson647, Heather Thorne103, Leigh B. Thorne176, Adrian Thorogood424, Grace Tiao8, Nebojsa Tijanic284, Lee E. Timms272, Roberto Tirabosco648, Marta Tojo106, Stefania Tommasi649, Christopher W. Toon170, Umut H. Toprak48,650, David Torrents57,81, Giampaolo Tortora651,652, Jörg Tost653, Yasushi Totoki118, David Townend654, Nadia Traficante103, Isabelle Treilleux655,656, Jean-Rémi Trotta61, Lorenz H. P. Trümper469, Ming Tsao124,539, Tatsuhiko Tsunoda183,657,658,659, Jose M. C. Tubio104,105,106, Olga Tucker660, Richard Turkington661, Daniel J. Turner513, Andrew Tutt323, Masaki Ueno376, Naoto T. Ueno662, Christopher Umbricht151,213,663, Husen M. Umer305,664, Timothy J. Underwood665, Lara Urban59,60, Tomoko Urushidate616, Tetsuo Ushiku339, Liis Uusküla-Reimand666,667, Alfonso Valencia57,81, David J. Van Den Berg166, Steven Van Laere307, Peter Van Loo290,291, Erwin G. Van Meir668, Gert G. Van den Eynden307, Theodorus Van der Kwast123, Naveen Vasudev137, Miguel Vazquez57,669, Ravikiran Vedururu267, Umadevi Veluvolu518, Shankar Vembu490,670, Lieven P. C. Verbeke506,671, Peter Vermeulen307, Clare Verrill351,672, Alain Viari177, David Vicente57, Caterina Vicentini177, K. Vijay Raghavan365, Juris Viksna673, Ricardo E. Vilain674, Izar Villasante57, Anne Vincent-Salomon635, Tapio Visakorpi190, Douglas Voet8, Paresh Vyas311,351, Ignacio Vázquez-García49,86,675,676, Nick M. Waddell209, Nicola Waddell209,311, Claes Wadelius677, Lina Wadi6, Rabea Wagener111,112, Jeremiah A. Wala8,14,82, Jian Wang56, Jiayin Wang1,40,66, Linghua Wang12, Qi Wang465, Wenyi Wang21, Yumeng Wang21, Zhining Wang220, Paul M. Waring523, Hans-Jörg Warnatz483, Jonathan Warrell5,19, Anne Y. Warren352,678, Sebastian M. Waszak60, David C. Wedge49,294,679, Dieter Weichenhan345, Paul Weinberger680, John N. Weinstein38, Joachim Weischenfeldt60,83,84, Daniel J. Weisenberger166, Ian Welch681, Michael C. Wendl1,10,11, Johannes Werner47,85, Justin P. Whalley61,682, David A. Wheeler12,13, Hayley C. Whitaker117, Dennis Wigle683, Matthew D. Wilkerson518, Ashley Williams244, James S. Wilmott211, Gavin W. Wilson6,148, Julie M. Wilson148, Richard K. Wilson1,684, Boris Winterhoff685, Jeffrey A. Wintersinger17,127,384, Maciej Wiznerowicz686,687, Stephan Wolf688, Bernice H. Wong689, Tina Wong1,30, Winghing Wong690, Youngchoon Woo250, Scott Wood209,311, Bradly G. Wouters44, Adam J. Wright6, Derek W. Wright133,691, Mark H. Wright217, Chin-Lee Wu72, Dai-Ying Wu285, Guanming Wu692, Jianmin Wu170, Kui Wu56,396, Yang Wu179,180, Zhenggang Wu64, Liu Xi12, Tian Xia693, Qian Xiang76, Xiao Xiao66, Rui Xing497, Heng Xiong56,396, Qinying Xu209,311, Yanxun Xu694, Hong Xue64, Shinichi Yachida118,695, Sergei Yakneen60, Rui Yamaguchi375, Takafumi N. Yamaguchi6, Masakazu Yamamoto120, Shogo Yamamoto89, Hiroki Yamaue376, Fan Yang490, Huanming Yang56, Jean Y. Yang696, Liming Yang220, Lixing Yang697, Shanlin Yang306, Tsun-Po Yang270, Yang Yang369, Xiaotong Yao408,698, Marie-Laure Yaspo483, Lucy Yates49, Christina Yau156, Chen Ye56,396, Kai Ye40,41, Venkata D. Yellapantula20,86, Christopher J. Yoon249, Sung-Soo Yoon463, Fouad Yousif6, Jun Yu699, Kaixian Yu700, Willie Yu701, Yingyan Yu702, Ke Yuan223,510,703, Yuan Yuan21, Denis Yuen6, Takashi Yugawa617, Christina K. Yung76, Olga Zaikova704, Jorge Zamora49,104,105,106, Marc Zapatka397, Jean C. Zenklusen220, Thorsten Zenz67, Nikolajs Zeps705,706, Cheng-Zhong Zhang8,707, Fan Zhang381, Hailei Zhang8, Hongwei Zhang494, Hongxin Zhang121, Jiashan Zhang220, Jing Zhang5, Junjun Zhang76, Xiuqing Zhang56, Xuanping Zhang66,369, Yan Zhang5,708,709, Zemin Zhang381,710, Zhongming Zhao711, Liangtao Zheng381, Xiuqing Zheng381, Wanding Zhou615, Yong Zhou56, Bin Zhu240, Hongtu Zhu700,712, Jingchun Zhu24, Shida Zhu56,396, Lihua Zou713, Xueqing Zou49, Anna deFazio246,247,714, Nicholas van As221, Carolien H. M. van Deurzen715, Marc J. van de Vijver523, L. van’t Veer716 & Christian von Mering433,717, The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts.

Objectives To examine the relationship between patients’ transfer ability and fall risk in stroke patients during hospitalization. Materials and methods We retrospectively enrolled 237 stroke patients who were transferred to a convalescent rehabilitation ward from acute wards in the same hospital. Using incident reports, we investigated their fall rates and activity status at the falls according to their transfer abilities, which were assessed with Functional Independence Measure (FIM) transfer scores. The bi-weekly time trend of fall rates in all patients and in three subgroups based on FIM transfer scores of 1–3, 4–5, and 6–7, and activity status at the falls, were investigated. In addition, changes of patients’ transfer ability on admission, at the first fall, and at discharge were investigated among falling patients. Results The fall rate was the greatest in patients with a FIM transfer score of 4 (14.3 times/1000 person-days). The majority of falls for patients with a FIM transfer score of 1 occurred at the activity status of “on the bed” and “sitting”, while three quarters of patients with a FIM score of 7 had falls during “standing” and “walking”. No longitudinal trend in fall rates was found overall; however, the fall rate trends differed depending on the FIM transfer score. The majority of the patients who fell required full assistance for transfers upon admission but required no assistance at discharge. Conclusions Fall risk differed among patients with various transfer abilities; the greatest risk was in those who needed minimal assistance for transfers.

Background: Near-infrared (NIR) fluorescence image-guided surgery (FIGS) introduces a revolutionary new approach to address this basic challenge in minimally invasive surgery. However, current FIGS systems have some limitations - the infrared rays cannot detect and visualise thick tissues with low concentrations of the fluorescent agent. We established a novel laparoscopic fluorescence spectrum (LFS) system using indocyanine green (ICG) fluorescence to overcome these limitations.& nbsp;Materials and Methods: Bovine serum albumin (BSA) was conjugated to ICG, and the mixtures were serially diluted at 5 x 10(-8)-5 x 10(-1) mg/mL. We used the LFS system and a NIR camera system (NLS; SHINKO OPTICAL CO., LTD Tokyo, Japan) to determine the optical dilution for the fluorescence detection. BSA was conjugated to ICG (5.0 x 10(-2) mg/mL) and used to coat the clips. We attempted to identify the fluorescence-coated clip from the serosal side of the cadaveric porcine stomach tissues using the LFS system and the NIR camera system. We measured the depth of the cadaveric porcine stomach wall at the thickest part that could be confirmed.& nbsp;Results: We could not visualise fluorescence concentrations < 2.5 x 10(-3) mg/mL using the NIR camera system. The spectrum was detected at a concentration < 2.5 x 10(-3) mg/mL. We were able to identify the spectrum of ICG (829 nm) to a 13-mm depth of cadaveric porcine stomach wall by using the LFS system but could not identify the same with the NIR camera system regardless of wall thickness.& nbsp;Conclusions: The novel LFS system with NIR fluorescence imaging in this ex vivo and cadaveric porcine model was confirmed useful at deeper depths and lower concentrations. Based on these findings, we anticipate that the LFS system can be integrated and routinely used in minimally invasive surgery.

Splenic infarction (SI) following gastrectomy is common; severe complications related to SI, such as splenic haemorrhage, abscess formation or rupture, can be fatal. To overcome these problems, we performed real-time vessel navigation using indocyanine green (ICG) fluorescence during robotic distal gastrectomy (RDG). The aim of study is to report the efficacy of robotic real-time vessel navigation for lymph node dissection (LND) along left gastroepiploic vessels (LGEVs). We treated seven patients with gastric cancer who underwent LND along the LGEVs using robotic real-time vessel navigation during RDG at our institution from January 2021 to July 2021. There were no complications (Clavien-Dindo classification II). There were no cases of post-operative SI or spleen-related complications. Robotic real-time vessel navigation using ICG for LND along LGEVs during RDG could help to reduce post-operative spleen-related complications associated with RDG.

Recently, laparoscopic surgery (LS) has become a more common procedure than traditional open surgery. Although LS-related adverse events have been reported, there is no formal, standardized curriculum to teach the fundamentals of LS in Japan. Understanding surgeons' knowledge regarding LS is crucial for developing an educational curriculum. The purpose of this study was to determine the baseline knowledge on LS of surgeons and surgical trainees in Japan.Participants completed 24 multiple-choice questions testing basic cognitive knowledge of LS and a questionnaire regarding the status of laparoscopic education. The examination was developed according to the 13 content domains of the Fundamentals of Laparoscopic Surgery (FLS) program. Scores were compared between post-graduate year (PGY) 5 and PGY 1-5 participants. Data are expressed as median scores and interquartile ranges. Wilcoxon signed-rank test was used for statistical analysis.A total of 195 surgeons and surgical trainees from 10 teaching hospitals (PGY1-5: 66, PGY 5: 129) across Japan completed the examination. The median score in the entire cohort was 75 [67; 83] %, with significantly higher scores in the PGY 5 group compared to the PGY1-5 group (79 [75; 83] % vs. 67 [58; 75] %, p 0.001). The differences in performance were due to better scores for PGY 5 group on the sections "equipment," "patient considerations," "abdominal access," "tissue handling," "hemorrhage and hemostasis," "tissue approximation," and "exiting the abdomen." Overall, the median scores in the "energy sources" and "establishment and physiology of the pneumoperitoneum" subsections were lower than in other domains. All participants agreed on the need for fundamental knowledge and a formal educational curriculum.Compared to experienced surgeons, surgical trainees had lesser knowledge about performing LS. Regardless of the years of experience, there are crucial knowledge gaps in specific areas regarding safe LS that should be addressed by implementing an educational curriculum.

Objective Although lung squamous cell carcinoma (SCC) accounts for 20-30% of lung cancer cases, new treatment options are limited. The CA031 study showed that nanoparticle albumin-bound-paclitaxel (nab-PTX) plus carboplatin produced a significantly higher overall response rate (41%) than solvent-based paclitaxel plus carboplatin in patients with lung SCC. However, the safety and efficacy of combination chemotherapy of nab-PTX and carboplatin has not yet been established for patients with concurrent lung SCC and idiopathic interstitial pneumonias (IIPs). The aim of this study was to assess the safety and efficacy profiles of nab-PTX and carboplatin in patients with lung SCC and concurrent IIPs. Methods Eight patients with inoperable-stage lung SCC and IIPs were treated with nab-PTX plus carboplatin in a first-line setting between June 2013 and December 2016. One of the eight was a woman, and the median age was 77 (range=72-80) years. Their clinical outcomes, including chemotherapy-associated acute exacerbation of IIPs, were retrospectively investigated. Results The overall response rate was 50%, the median progression-free survival time was 5.6 months, and the median overall survival time was 8.1 months. No patients experienced chemotherapy-related exacerbation of IIPs in the first-line treatment with nab-PTX plus carboplatin. However, IIPs worsened in two of four patients who received second-line chemotherapy. Conclusion Combination chemotherapy of nab-PTX and carboplatin may be an effective and safe treatment option for patients with inoperable lung SCC with IIPs. To confirm this, a large-scale prospective study is needed.

Background: Conversion surgery (CS) is expected as a new therapeutic strategy for patients with unresectable pancreatic cancer (UR-PC). We analyzed outcomes of CS for patients with UR-PC and evaluated the survival benefit of CS. Methods: Thirty-four patients diagnosed with UR-PC according to the National Comprehensive Cancer Network guideline underwent CS in our hospital. Resectability was considered by multimodal images in patients who underwent nonsurgical treatment (NST) for more than 6 months. CS was performed only in patients who were judged to be able to undergo R0 resection. Results: Twenty-six patients had locally advanced PC, and eight had distant metastases. The median duration of NST was 9 (range 5-44) months. R0 resection was achieved in 30 patients (88.2%). Six patients (17.6%) showed Evans grade ≥III. Three- and 5-year overall survival (OS) rates from initial treatment were 74% and 56.9%, respectively, with median survival time (MST) of 5.3 years. The actual 5-year OS rate in 19 patients was 47.4% with an MST of 4.0 years. Patients with Evans grade ≥III had a better prognosis than those with Evans grade

Background The British Thoracic Society guidelines for diagnostic flexible bronchoscopy (FB) in adults recommend that intravenous sedation should be offered to patients undergoing bronchoscopy. However, it is difficult to determine the adequate depth of sedation for each patient because of inter-individual variability. Methods This prospective, open-label, single-arm study was conducted in patients undergoing routine bronchus examination with FB. All patients underwent FB under local anesthesia and conscious sedation, with initial administration of 0.03 mg/kg midazolam. The sedation level during FB was objectively assessed using the Ramsay sedation score (RSS). Two hours after the procedure, patients completed a questionnaire about its efficacy and adverse effects using a visual analog scale (VAS). Receiver operating characteristic (ROC) curve analyses were performed to determine the optimal RSS that could improve the subjective efficacy indicated by the VAS. Results This study enrolled 110 consecutive patients between September 2008 and February 2012. The median total amount of midazolam administered was 1.65 mg per patient. In an analysis of ROC curves between RSS and VAS, the area under the ROC curve for an RSS of 4 against the others was 0.66 (95% CI: 0.54 to 0.77, p = 0.014). The area under the ROC curve was not shown to be statistically significant for RSSs other than 4. Conclusions The optimal depth of conscious sedation during FB for conventional examination was achieved at an RSS of 4. The patients’ subjective evaluations indicated that a deep level of conscious sedation does not seem necessary for FB.

Background Despite its advantages, few trainees outside of North America have access to simulation training. We hypothesized that a stepwise training method using tele-mentoring system would be an efficient technique for training in basic laparoscopic skills. Methods Residents were randomized into two groups and trained to proficiency in intracorporeal suturing. The stepwise group (SG) practiced the task step-by-step, while the other group practiced comprehensively (CG). Each participant received weekly coaching via two-way web conferencing software. The duration of the coaching sessions and self-practice time were compared between the two groups. Results Twenty residents from 15 institutions participated, and all achieved proficiency. Coaching sessions using tele-mentoring system were completed without difficulties. The SG required significantly shorter coaching time per session than the CG (p = .002). There was no significant difference in self-practice time. Conclusions The stepwise training method with the tele-mentoring system appears to make efficient use of surgical trainees' and trainers' time.

Controversy remains regarding the optimal resection approach for Siewert type II adenocarcinoma of the esophagogastric junction (EGJ). Furthermore, an esophageal diverticulum, although rare, can complicate surgical procedures. Herein, we report a case of EGJ adenocarcinoma with an esophageal diverticulum that was treated using the minimally invasive abdominal and left thoracic approach (MALTA). A 72-year-old man, with EGJ adenocarcinoma and an epiphrenic diverticulum on esophagogastroduodenoscopy underwent endoscopic submucosal dissection. The pathological diagnosis of the specimen revealed invasion to the lymphatic vessels. Therefore, laparoscopic proximal gastrectomy and thoracoscopic lower esophagectomy with D1 lymph node dissection and double-tract reconstruction of the esophageal diverticulum were performed via MALTA. The patient was discharged without any postoperative morbidity. MALTA provides good visualization for the transection of the lower esophagus in cases of esophageal diverticulum. Moreover, MALTA for adenocarcinoma of the EGJ is technically feasible, even with the presence of a lower esophageal diverticulum.

Purpose: We used propensity score matching to compare the complication rates after laparoscopic total gastrectomy (LTG) with esophagojejunostomy (EJS) performed using a circular or a linear stapler. Methods: We retrospectively enrolled all patients who underwent curative LTG between November 2004 and March 2016. Patients were categorized into the circular and linear groups according to the stapler type used for the subsequent EJS. Patients in the groups were matched using the following propensity score covariates: age, sex, body mass index, American Society of Anesthesiologists physical status, extent of lymph node dissection, and Japanese Classification of Gastric Carcinoma stage. Clinicopathological characteristics and surgical outcomes were compared. Results: We identified 66 propensity score-matched pairs among 379 patients who underwent LTG. There was no significant between-group difference in the median operative time, extent of lymph node dissection, number of lymph nodes resected, rate of conversion to open surgery, or number of surgeries performed by a surgeon certified by the Japanese Society of Endoscopic Surgery. In the circular and linear groups, the rate of all complications (Clavien-Dindo [CD] classification ≥ I; 21 vs. 26%, respectively; p = 0.538), complications more severe than CD grade III (14 vs. 14%, respectively; p = 1.000), and occurrence of EJS leakage and stenosis more severe than CD grade III (5 vs. 2%, p = 0.301; 9 vs. 8%, p = 0.753, respectively) were comparable. Conclusions: There is no difference in the postoperative complication rate related to the type of stapler used for EJS after LTG.

Background The effect of botulinum toxin A (BoNTA) injection on flexed-elbow deformity is usually evaluated using the Modified Ashworth Scale (MAS), but only with the muscle tone at rest. Some patients show the flexed-elbow deformity during gait despite low muscle tone at rest. Objective This study aimed to evaluate the effect of BoNTA injection on flexed-elbow deformity during gait using a three-dimensional motion analysis system. Methods Twenty stroke patients with spastic flexed-elbow deformity during gait received BoNTA injections into the upper limb muscles. The MAS score of the elbow flexors, passive elbow range of motion, comfortable overground gait velocity, and elbow flexion angle during treadmill gait were evaluated just before and 2, 6, and 12 weeks after the injection. Twenty-five healthy subjects were also recruited to provide a normal reference of the elbow flexion angle. Results The MAS scores at 2, 6 and 12 weeks after the injection were significantly lower than that before the injection. Some patients showed no spasticity at rest but an obviously flexed elbow during gait. The elbow flexion angles during gait at 2 and 6 weeks after the injection were significantly lower than that before the injection. Conclusions BoNTA injections to the upper limb muscles reduced muscle tone at rest and flexed-elbow deformity during gait. However, the elbow flexion angle during gait returned to its pre-injection level sooner than the muscle tone at rest. We strongly recommend evaluating muscle tone during motion and at rest, preferably using three-dimensional motion analysis since it can objectively detect small changes.

Background We have reported the effectiveness of laparoscopy-assisted stomach-partitioning gastrojejunostomy Roux-en-Y reconstruction (LASPGJ-RY) for gastric outlet obstruction (GOO). The aim of this study was to evaluate the surgical outcomes of totally laparoscopic stomach-partitioning gastrojejunostomy Roux-en-Y reconstruction (TLSPGJ-RY) for GOO. Materials and methods This retrospective study enrolled 19 consecutive patients with GOO. Surgical outcomes of LASPGJ-RY (LA group; n=8) and TLSPGJ-RY (TL group; n=11) between January 2004 and 2015 were compared. The patients' background characteristics, operative findings, postoperative complications, and period to starting postoperative chemotherapy were examined. Results Eligible cases included 6 patients with gastric cancer, 4 with pancreatic cancer, 4 with duodenal cancer, 4 with urologic malignancies, and 1 with benign duodenal stenosis. The patients' background characteristics were not significantly different. In surgical outcomes, there were no significant differences in operating time, bleeding, complications (≥Clavien-Dindo grade IIIA), and postoperative hospital stay between the groups. The time to resume diet was significantly shorter in the TL group (median, 3 d; range, 3 to 6 d) than in the LA group (median, 5 d; range, 3 to 7 d; P=0.0093), and the number of patients who could receive chemotherapy after surgery was significantly higher in the TL group (P=0.039). Conclusions TLSPGJ-RY was a safe and feasible gastrojejunostomy procedure for GOO. TLSPGJ-RY might be useful for early resumption of oral intake after surgery.

Background It is important to understand pulmonary vein drainage pattern variations and their frequency in order to perform safe anatomical pulmonary resection. Methods Variations and frequencies were assessed using three-dimensional computed tomography angiography (3D-CT) in 194 patients. In cases where the tumor or lymph node caused atelectasis or compression of hilar structures, the involved lobes were excluded from the analyses. Results We confirmed variant drainage patterns in 15/189 (8.0%) patients in the right upper lobe (RUL), 29/189 (15.3%) in the right middle lobe (RML), 18/192 (9.5%) in the right lower lobe (RLL), and 5/187 (2.6%) in the left upper lobe (LUL). There was no variant type in the left lower lobe (LLL). There were 14 (7.4%) cases of anomalous superior posterior pulmonary vein of RUL (V2 ) drainage: V2 draining to the superior pulmonary vein (SPV) (n = 2, 1.1%), V2 to the inferior pulmonary vein (IPV) (n = 7, 3.7%), V2 to the left atrium (LA) (n = 2, 1.1%), and V6 to the apical pulmonary vein of the RLL (n = 3, 1.6%). There was a posterior pulmonary vein, V3 to RML pulmonary vein in one case (0.5%). The RML pulmonary vein drained into the IPV in 14 (7.4%) and into the LA in 15 (7.9%) cases. The right V6 directly drained into the LA in 15 (7.9%) and V6 into the SPV in 3 (1.6%) cases. The lingular pulmonary vein drained into the IPV in one case (0.5%) and into the LA in two cases (1.1%). The inferior lingular pulmonary vein V5 drained into the IPV and into the LA in one case (0.5%), respectively. Conclusion We describe anomalous pulmonary venous drainage patterns and their frequencies particular to anatomic surgical resection. 3D-CT is useful to find such variations.

BACKGROUND AND AIM Lymph node metastasis is an important prognostic factor for intrahepatic cholangiocarcinoma (ICC), but accurate preoperative diagnosis is difficult. The aim of this study was to measure the concentration of serum carbohydrate antigen 19-9 (s-CA19-9) as a preoperative predictor of lymph node metastasis. METHODS In our department, curative-intent hepatectomy for ICC has been performed only once the absence of metastases in para-aortic lymph nodes (PALN) has been confirmed from intraoperative frozen-section pathological examinations. The present study included 13 non-resected ICC patients with PALN metastasis (PALN group) and 44 resected ICC patients without PALN metastasis (non-PALN group). S-CA19-9 was examined to evaluate predictive performance for PALN metastasis and regional lymph node metastasis (pN1) from analysis of the receiver operating characteristic curve. In the non-PALN group, univariate and multivariate analyses for survival were performed on clinicopathological variables. RESULTS From receiver operating characteristic curve analysis, s-CA19-9 showed good diagnostic accuracy for PALN metastasis (68%; cut-off, 200 U/mL) and pN1 (77%; cut-off, 100 U/mL). In univariate analysis, age (

Background: Post-hepatectomy liver failure (PHLF) is a serious complication after major hepatectomy with extrahepatic bile duct resection (Hx with EBDR) that may cause severe morbidity and even death. The purpose of this study was to compare several criteria systems as predictors of PHLF-related mortality following Hx with EBDR for perihilar cholangiocarcinoma (PHCC). Methods: The study cohort consisted of 222 patients who underwent Hx with EBDR for PHCC. We compared several criteria systems, including previously established criteria (the International Study Group of Liver Surgery (ISGLS) criterion; and the “50-50” criterion), and our institution’s novel systems “Max T-Bili” defined as total bilirubin (T-Bili) >7.3 mg/dL during post-operative days (POD) 1–7, and the “3-4-50” criterion, defined as total bilirubin >4 mg/dL and prothrombin time Results: Thirteen patients (5.8%) died from PHLF-related causes. The 3-4-50 criterion showed high positive predictive values (39.1%), the 3-4-50, Max T-Bili, and 50-50 criterion showed high accuracies (91.7, 86.9, and 90.5%, respectively) and varying sensitivities (69.2, 69.2, and 38.5% respectively). Conclusions: The 3-4-50, Max T-Bili, and 50-50 criterion were all useful for predicting PHLF-related mortality after Hx with EBDR for PHCC.

In this work, electron backscatter diffraction and digital image correlation techniques were employed to study the microstructure and microstructure-property relationship in friction-stir welded TRIP steel. It was found that the thermal effect of the welding process led to material softening in the heat-affected zone and promoted martensite transformation in the stir zone. These microstructural changes provided rapid strain localization during subsequent transverse tensile tests and thus resulted in premature failure of the welds. Material softening in the heat-affected zone was deduced to be a combined result of dissolution and spheroidisation of retained austenite as well as recovery in bainitic ferrite. The stir zone martensite was characterized by significant orientation spread and therefore its orientation relationship with austenite essentially deviated from the ideal Kurdjumov-Sachs relation. Moreover, the martensite transformation was found to be influenced by variant selection.

Surgical education has seen tremendous changes in the US over the past decade. The Halstedian training model of see one, do one, teach one that governed surgical training for almost 100 years has been replaced by the achievement of the ACGME competencies, milestones, entrustable professional activities (EPAs), and acquisition of surgical skill outside the operating room on simulators. Several of these changes in American medical education have been influenced by educators and training paradigms abroad. In this paper, we review the training paradigms for surgeons in the UK, Japan, and Mexico to allow comparisons with the US training paradigm and promote the exchange of ideas.

Background Whether to classify “advanced (subserosal layer or greater invasion)” biliary carcinoma centered in the cystic duct (BCCD) as gallbladder carcinoma (GBC) or perihilar cholangiocarcinoma (PHCC) remains unclear. Methods The clinicopathological features and overall survival (OS) of patients with advanced BCCD were examined through a comparison with those of patients with advanced PHCC and with GBC. Results 290 patients were classified as 199 PHCC, 44 GBC, and 47 BCCD. Patients with BCCD (median, 23 months) had significantly worse OS than those with PHCC (44 months, p = 0.030). OS of patients with BCCD, all of whom were classified as pT3 or pT4 by the American Joint Committee on Cancer (AJCC) classification of GBC, was similar to 27 patients with pT3 or pT4 GBC (23 months, p = 0.840). When the patients with BCCD were classified by the AJCC classification of PHCC, 36 were classified as pT2. OS among the patients with BCCD classified as pT2 by the PHCC classification (29 months) was significantly worse than that among patients classified as pT2 PHCC (48 months, p = 0.040). Conclusion These findings suggest that advanced BCCD is appropriately classified as a subtype of GBC because it can grow through the serosa.

Curative endoscopic resection of non-ampullary duodenal lesions, although possible, is challenging. In recent years, although a novel surgical technique named laparoscopic-endoscopic cooperative surgery (LECS), which combines laparoscopic and endoscopic techniques, has made the resection of nonampullary duodenal lesions relatively easier, closure of the defect is still controversial. We report two cases of the duodenal lesion which were closed using a novel technique for primary closure utilising the free wall of the duodenum. Two cases of the duodenal lesion in the second portion of the duodenum were undergone full thickness resection using the LECS technique. The defect is designed spirally to ensure maximum use of the free wall of the duodenum. The mucosal layer is closed using a running suture, and the seromuscular layer is closed using interrupted sutures. The suture line is then reinforced with omentum. There were no intraoperative complications and had uneventful post-operative courses with no leakage, stenosis, or relapse.

Purpose: To establish the within-day and between-day intra-rater reliability, inter-rater reliability, validity and systematic errors of the tandem gait test (TGT).Materials and methods: Thirty par...

// Shoki Sato 1 , Toru Nakamura 1 , Toyomasa Katagiri 2 , Takahiro Tsuchikawa 1 , Toshihiro Kushibiki 1 , Kouji Hontani 1 , Mizuna Takahashi 1 , Kazuho Inoko 1 , Hironobu Takano 1 , Hirotake Abe 1 , Shintaro Takeuchi 1 , Masato Ono 1 , Shota Kuwabara 1 , Kazufumi Umemoto 1 , Tomohiro Suzuki 1 , Osamu Sato 1 , Yusuke Nakamura 3 and Satoshi Hirano 1 1 Department of Gastroenterological Surgery II, Hokkaido University Graduate School of Medicine, Sapporo, Japan 2 Division of Genome Medicine, Institute for Genome Research, Tokushima University, Tokushima, Japan 3 Department of Medicine and Surgery, The University of Chicago, Chicago, IL, USA Correspondence to: Toru Nakamura, email: torunakamura@med.hokudai.ac.jp Keywords: C16orf74; pancreatic ductal adenocarcinoma; cell-permeable peptide; molecular target therapy Received: May 04, 2017 Accepted: July 26, 2017 Published: October 19, 2017 ABSTRACT Background: Chromosome 16 open reading frame 74 ( C16orf74 ) is highly expressed in pancreatic ductal adenocarcinoma (PDAC) and is involved in cancer cell proliferation and invasion through binding to calcineurin (CN). Therefore, C16orf74 is a good target for the development of a PDAC treatment. A cell-permeable dominant-negative (DN) peptide that can inhibit the C16orf74/CN interaction was designed to examine whether this peptide can inhibit PDAC cell proliferation in vitro and in vivo . Method: TheDN-C16orf74 peptide, which corresponds to the portion of C16orf74 that interacts with CN, was synthesized, and we assessed its anti-tumor activity in proliferation assays with human PDAC cells and the underlying molecular signaling pathway. Using an orthotopic xenograft model of PDAC, we treated mice intraperitoneally with phosphate-buffered saline (PBS), control peptide, or DN-C16orf74 and analyzed the tumor-suppressive effects. Result: DN-C16orf74 inhibited the binding of C16orf74 to CN in an immunoprecipitation assay. DN-C16orf74 suppressed PDAC cell proliferation, and the level of suppression depended on the expression levels of C16orf74 in vitro . DN-C16orf74 also exhibited anti-tumor effects in orthotopic xenograft model. Furthermore, the tumor-suppressive effect was associated with inhibition of the phosphorylation of Akt and mTOR. Conclusion: The cell-permeable peptide DN-C16orf74 has a strong anti-tumor effect against PDAC in vitro and in vivo .

The purpose of this study was to determine absolute protein expression levels of transporters at the porcine inner blood-retinal barrier (BRB) and to compare the transporter protein expression quantitatively among the inner BRB, outer BRB, blood-brain barrier (BBB), and blood-cerebrospinal fluid barrier (BCSFB). Crude membrane fractions of isolated retinal capillaries (inner BRB) and isolated retinal pigment epithelium (RPE, outer BRB) were prepared from porcine eyeballs, while plasma membrane fractions were prepared from isolated porcine brain capillaries (BBB) and isolated choroid plexus (BCSFB). Protein expression levels of 32 molecules, including 16 ATP-binding-cassette (ABC) transporters and 13 solute-carrier (SLC) transporters, were measured using a quantitative targeted absolute proteomic technique. At the inner BRB, five molecules were detected: breast cancer resistance protein (BCRP, ABCG2; 22.8 fmol/μg protein), multidrug resistance protein 1 (MDR1, ABCB1; 8.70 fmol/μg protein), monocarboxylate transporter 1 (MCT1, SLC16A1; 4.83 fmol/μg protein), glucose transporter 1 (GLUT1, SLC2A1; 168 fmol/μg protein), and sodium-potassium adenosine triphosphatase (Na

We herein report the case of a 78-year-old woman with an intraductal tumor with scant mucin production in a moderately dilated main pancreatic duct that resembled an intraductal tubulopapillary neoplasm (ITPN) on imaging. An endoscopic transpapillary forceps biopsy enabled an accurate preoperative diagnosis of the tumor as an oncocytic type intraductal papillary mucinous neoplasm (IPMN) of the pancreas microscopically showing papillary growth consisting of oncocytic cells with a typical mucin expression profile, although with few intraepithelial lumina containing mucin. This is the first case of an oncocytic type IPMN mimicking an ITPN that was able to be diagnosed preoperatively.