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Neuroendocrine neoplasms (NENs) are rare neoplasms that occur in various organs and present with diverse clinical manifestations. Pathological classification is important in the diagnosis of NENs. Treatment strategies must be selected according to the status of differentiation and malignancy by accurately determining whether the neoplasm is functioning or nonfunctioning, degree of disease progression, and presence of metastasis. The newly revised Clinical Practice Guidelines for Gastroenteropancreatic Neuroendocrine Neoplasms (GEP-NENs) comprises 5 chapters—diagnosis, pathology, surgical treatment, medical and multidisciplinary treatment, and multiple endocrine neoplasia type 1 (MEN1)/von Hippel–Lindau (VHL) disease—and includes 51 clinical questions and 19 columns. These guidelines aim to provide direction and practical clinical content for the management of GEP-NEN preferentially based on clinically useful reports. These revised guidelines also refer to the new concept of “neuroendocrine tumor” (NET) grade 3, which is based on the 2017 and 2019 WHO criteria; this includes health insurance coverage of somatostatin receptor scintigraphy for NEN, everolimus for lung and gastrointestinal NET, and lanreotide for GEP-NET. The guidelines also newly refer to the diagnosis, treatment, and surveillance of NEN associated with VHL disease and MEN1. The accuracy of these guidelines has been improved by examining and adopting new evidence obtained after the first edition was published.

To determine acceptable limits of communication delays in telesurgery, we investigated the impact of communication delays under a dynamic environment using a surgical assist robot. Previous studies have evaluated acceptable delays under static environments. Effects of delays may be enhanced in dynamic environments, but studies have not yet focused on this point. Thirty-four subjects with different surgical experience (Group1: no surgical experience; Group2: only laparoscopic surgical experience; Group3: robotic surgery experience) performed 4 tasks under different delays (0, 70, 100, 150, 200, or 300 ms) using a surgical assist robot. Task accomplishment time and total movement distance of forceps were recorded and compared under different communication delays of 0-300 ms. In addition, surgical performance was compared between Group1or Group2 without delay and Group3 with communication delays. Significant differences in task accomplishment time were found between delays of 0 and 70 ms, but not between delays of 70 and 100 ms. Thereafter, the greater the communication delay, the longer the task accomplishment time. Similar results were obtained in total movement distance of forceps. Comparisons between Group3 with delay and Group1 or Group2 without delay demonstrated that surgical performance in Group3 with delay was superior or equal to that of Group1 or Group2 without delay as long as the delay was 100 ms or less. Communication delays in telesurgery may be acceptable if 100 ms or less. Experienced surgeons with more than 100 ms of delay could outperform less-experienced surgeons without delay.

Confirming the patient benefit of progression-free survival (PFS) in B-cell non-Hodgkin lymphoma (B-NHL) and multiple myeloma (MM) has become increasingly challenging due to the improved outcomes brought by novel therapies. In parallel, the U.S. Food and Drug Administration recommends conducting randomized trials, focusing on evaluating early endpoints to compare study and control arms for accelerated approval (AA). From both the clinical and regulatory perspectives, identifying early surrogate endpoints for PFS is imperative. In principle, the complete response rate (CRR) is a potential early endpoint for granting AA. This study aimed to evaluate whether the CRR is a surrogate early endpoint for PFS in patients with B-cell malignancies. We investigated the results of randomized trials with data on CRR and PFS using a combined approach of PubMed and Clinical Trial.gov (CTG), identifying 52 trials after applying exclusion criteria. A meta-regression plot showed a significant correlation between the CRR and PFS with an R-squared of 0.822 in 13 trials of aggressive B-NHL, 0.941 in the 8 trials of indolent N-NHL and 0.492 in the 31 trials of MM. This meta-analysis suggests that the CRR can be considered an early surrogate endpoint for PFS in B-NHL and MM.

Although adjuvant chemotherapy with gemcitabine is standard care for resected pancreatic cancer, S-1 has shown non-inferiority to gemcitabine for advanced disease. We aimed to investigate the non-inferiority of S-1 to gemcitabine as adjuvant chemotherapy for pancreatic cancer in terms of overall survival. We did a randomised, open-label, multicentre, non-inferiority phase 3 trial undertaken at 33 hospitals in Japan. Patients who had histologically proven invasive ductal carcinoma of the pancreas, pathologically documented stage I–III, and no local residual or microscopic residual tumour, and were aged 20 years or older were eligible. Patients with resected pancreatic cancer were randomly assigned (in a 1:1 ratio) to receive gemcitabine (1000 mg/m2, intravenously administered on days 1, 8, and 15, every 4 weeks [one cycle], for up to six cycles) or S-1 (40 mg, 50 mg, or 60 mg according to body-surface area, orally administered twice a day for 28 days followed by a 14 day rest, every 6 weeks [one cycle], for up to four cycles) at the data centre by a modified minimisation method, balancing residual tumour status, nodal status, and institutions. The primary outcome was overall survival in the two treatment groups, assessed in the per-protocol population, excluding ineligible patients and those not receiving the allocated treatment. The protocol prespecified that the superiority of S-1 with respect to overall survival was also to be assessed in the per-protocol population by a log-rank test, if the non-inferiority of S-1 was verified. We estimated overall and relapse-free survival using the Kaplan-Meier methods, and assessed non-inferiority of S-1 to gemcitabine using the Cox proportional hazard model. The expected hazard ratio (HR) for mortality was 0·87 with a non-inferiority margin of 1·25 (power 80%; one-sided type I error 2·5%). This trial is registered at UMIN CTR (UMIN000000655). 385 patients were randomly assigned to treatment between April 11, 2007, and June 29, 2010 (193 to the gemcitabine group and 192 to the S-1 group). Of these, three were exlcuded because of ineligibility and five did not receive chemotherapy. The per-protocol population therefore consisted of 190 patients in the gemcitabine group and 187 patients in the S-1 group. On Sept 15, 2012, following the recommendation from the independent data and safety monitoring committee, this study was discontinued because the prespecified criteria for early discontinuation were met at the interim analysis for efficacy, when all the protocol treatments had been finished. Analysis with the follow-up data on Jan 15, 2016, showed HR of mortality was 0·57 (95% CI 0·44–0·72, pnon-inferiority<0·0001, p<0·0001 for superiority), associated with 5-year overall survival of 24·4% (18·6–30·8) in the gemcitabine group and 44·1% (36·9–51·1) in the S-1 group. Grade 3 or 4 leucopenia, neutropenia, aspartate aminotransferase, and alanine aminotransferase were observed more frequently in the gemcitabine group, whereas stomatitis and diarrhoea were more frequently experienced in the S-1 group. Adjuvant chemotherapy with S-1 can be a new standard care for resected pancreatic cancer in Japanese patients. These results should be assessed in non-Asian patients. Pharma Valley Center, Shizuoka Industrial Foundation, Taiho Pharmaceutical.

PurposeWe reviewed the literature regarding the specific methods and strategies for implementing simulation-based training into the modern surgical residency curriculum. Residency programs are still struggling with how best to implement it into their curricula from a practical viewpoint.MethodsA systematic review was performed using Ovid MEDLINE, EMBASE, PubMed, PsycINFO, Web of Science, and other resources for studies involving the use of simulation for technical skills training in the surgical residency curriculum. Studies were selected based on the integration of simulation into the curriculum and/or a description of the details of implementation and the resources required.ResultsIn total, 2533 unique citations were retrieved based on this search, and 31 articles met the inclusion criteria. Most simulators were focused on laparoscopic procedures, and training occurred most often in a skills lab. The assessment of skills consisted mostly of speed of task completion. Only 4 studies addressed issues of cost, and 6 programs mentioned human resources without any mention of skills center personnel or administrative support.ConclusionsAll of the studies described the nature of the simulation training, but very few commented on how it was actually implemented and what was needed from organizational, administrative and logistical perspectives.

PurposeWe investigated the communication bandwidth (CB) limitation for remote robotics surgery (RRS) using hinotori™ (Medicaroid, Kobe, Japan).MethodsThe operating rooms of the Hokkaido University Hospital and Kyushu University Hospital were connected using the Science Information NETwork (SINET). The minimum required CB for the RRS was verified by decreasing the CB from 500 to 100 Mbps. Ten surgeons were tested on a task (intracorporeal suturing) at different levels of video compression (VC) (VC1: 120 Mbps, VC2: 40 Mbps, VC3: 20 Mbps) with the minimum required CB, and assessed based on the task completion time, Global Evaluative Assessment of Robotic Skills (GEARS), and System and Piper Fatigue Scale-12 (PFS-12).ResultsPacket loss was observed at 3–7% and image degradation was observed at 145 Mbps CB. The task performance with VC1 was significantly worse than that with VC2 and VC3 according to the task completion time (VC1 vs VC2, P = 0.032; VC1 vs. VC3, P = 0.032), GEARS (VC1 vs VC2; P = 0.029, VC1 vs VC3; P = 0.031), and PFS-12 (VC1 vs. VC2; P = 0.032, VC1 vs. VC3; P = 0.032) with 145 Mbps.ConclusionOur findings provide evidence that RRS using hinotori™ requires a CB ≥ 150 Mbps. We also found that when there is insufficient CB, RRS can be continued by compressing the image.

Hidewaki Nakagawa and colleagues report a comprehensive genome-wide mutational landscape of 300 liver cancers from Japanese individuals. They identify candidate driver mutations, including ones in noncoding regions, and structural mutations affecting the expression of nearby genes. Liver cancer, which is most often associated with virus infection, is prevalent worldwide, and its underlying etiology and genomic structure are heterogeneous. Here we provide a whole-genome landscape of somatic alterations in 300 liver cancers from Japanese individuals. Our comprehensive analysis identified point mutations, structural variations (STVs), and virus integrations, in noncoding and coding regions. We discovered mutational signatures related to liver carcinogenesis and recurrently mutated coding and noncoding regions, such as long intergenic noncoding RNA genes ( NEAT1 and MALAT1 ), promoters, CTCF-binding sites, and regulatory regions. STV analysis found a significant association with replication timing and identified known ( CDKN2A , CCND1 , APC , and TERT ) and new ( ASH1L , NCOR1 , and MACROD2 ) cancer-related genes that were recurrently affected by STVs, leading to altered expression. These results emphasize the value of whole-genome sequencing analysis in discovering cancer driver mutations and understanding comprehensive molecular profiles of liver cancer, especially with regard to STVs and noncoding mutations.

PurposeIn recent years, the expectations for telesurgery have grown with the development of robot-assisted surgical technology and advances in communication technology. To verify the feasibility of the social implementation of telesurgery, we evaluated the communication integrity, availability, and communication delay of robotic surgery by remote control under different communication conditions of commercial lines.MethodsA commercial line was used to connect hospitals 150 km apart. We had prepared guaranteed-type lines (1Gbps, 10Mbps, 5Mbps) and best effort-type lines. Two types of robotic teleoperations were performed, and we evaluated the round-trip time (RTT) of communication, packet loss, and glass-to-glass time.ResultsThe communication delay was 4 ms for the guaranteed-type line and 10 ms for the best effort-type line. Packet loss occurred on the 5 Mbps guaranteed-type line. The mean glass-to-glass time was 92 ms for the guaranteed-type line and 95 ms for the best effort-type line. There was no significant difference in the number of errors in the task according to the type of line or the bandwidth speed.ConclusionsThe social implementation of telesurgery using the currently available commercial communication network is feasible.