Laparoscopic Hepatectomy: Current State in Japan Based on the 4th Nationwide Questionnaire

Purpose. Since laparoscopic hepatectomy (LH) became covered by national health insurance in April 2010 in Japan, the numbers of applied cases and institutions performing it have increased and the indication has expanded. We surveyed the current state and safety of LH in Japan. Methods. A questionnaire survey was performed in 41 institutions related to the Japanese Endoscopic Liver Surgery Study Group and 747 institutions certified by the Japanese Society of Gastroenterological Surgery, and responses concerning all 2962 cases of LH performed by August 2011 were obtained. Results. The surgical procedure employed was hemihepatectomy in 234 (8%), segmentectomy in 88 (3%), left lateral segmentectomy in 434 (15%), segmentectomy in 156 (5%), and partial resection in 1504 (51%) cases. The approach was pure laparoscopy in 1835 (63%), hand-assisted laparoscopic surgery in 201 (7%), and laparoscopy-assisted surgery in 926 (31%). Regarding perioperative complications, surgery was switched to laparotomy in 59 (2.0%), reoperation was performed in 4 (0.1%), and surgery-related death occurred in 2 (0.07%). Intraoperative accidents occurred in 68 (2.3%), and postoperative complications developed in 94 (3.2%). Conclusions. When the selection of cases is appropriate, LH for liver diseases can be safely performed

Deletion of both p62 and Nrf2 spontaneously results in the development of nonalcoholic steatohepatitis

Nonalcoholic steatohepatitis (NASH) is one of the leading causes of chronic liver disease worldwide. However, details of pathogenetic mechanisms remain unknown. Deletion of both p62/Sqstm1 and Nrf2 genes spontaneously led to the development of NASH in mice fed a normal chow and was associated with liver tumorigenesis. The pathogenetic mechanism (s) underlying the NASH development was investigated in p62:Nrf2 double-knockout (DKO) mice. DKO mice showed massive hepatomegaly and steatohepatitis with fat accumulation and had hyperphagia-induced obesity coupled with insulin resistance and adipokine imbalance. They also showed dysbiosis associated with an increased proportion of gram-negative bacteria species and an increased lipopolysaccharide (LPS) level in feces. Intestinal permeability was elevated in association with both epithelial damage and decreased expression levels of tight junction protein zona occludens-1, and thereby LPS levels were increased in serum. For Kupffer cells, the foreign body phagocytic capacity was decreased in magnetic resonance imaging, and the proportion of M1 cells was increased in DKO mice. In vitro experiments showed that the inflammatory response was accelerated in the p62:Nrf2 double-deficient Kupffer cells when challenged with a low dose of LPS. Diet restriction improved the hepatic conditions of NASH in association with improved dysbiosis and decreased LPS levels. The results suggest that in DKO mice, activation of innate immunity by excessive LPS flux from the intestines, occurring both within and outside the liver, is central to the development of hepatic damage in the form of NASH

Genomic characterization of biliary tract cancers identifies driver genes and predisposing mutations

Background & Aims Biliary tract cancers (BTCs) are clinically and pathologically heterogeneous and respond poorly to treatment. Genomic profiling can offer a clearer understanding of their carcinogenesis, classification and treatment strategy. We performed large-scale genome sequencing analyses on BTCs to investigate their somatic and germline driver events and characterize their genomic landscape. Methods We analyzed 412 BTC samples from Japanese and Italian populations, 107 by whole-exome sequencing (WES), 39 by whole-genome sequencing (WGS), and a further 266 samples by targeted sequencing. The subtypes were 136 intrahepatic cholangiocarcinomas (ICCs), 101 distal cholangiocarcinomas (DCCs), 109 peri-hilar type cholangiocarcinomas (PHCs), and 66 gallbladder or cystic duct cancers (GBCs/CDCs). We identified somatic alterations and searched for driver genes in BTCs, finding pathogenic germline variants of cancer-predisposing genes. We predicted cell-of-origin for BTCs by combining somatic mutation patterns and epigenetic features. Results We identified 32 significantly and commonly mutated genes including TP53 , KRAS , SMAD4 , NF1 , ARID1A , PBRM1 , and ATR , some of which negatively affected patient prognosis. A novel deletion of MUC17 at 7q22.1 affected patient prognosis. Cell-of-origin predictions using WGS and epigenetic features suggest hepatocyte-origin of hepatitis-related ICCs. Deleterious germline mutations of cancer-predisposing genes such as BRCA1 , BRCA2 , RAD51D , MLH1 , or MSH2 were detected in 11% (16/146) of BTC patients. Conclusions BTCs have distinct genetic features including somatic events and germline predisposition. These findings could be useful to establish treatment and diagnostic strategies for BTCs based on genetic information. Lay summary We here analyzed genomic features of 412 BTC samples from Japanese and Italian populations. A total of 32 significantly and commonly mutated genes were identified, some of which negatively affected patient prognosis, including a novel deletion of MUC17 at 7q22.1 . Cell-of-origin predictions using WGS and epigenetic features suggest hepatocyte-origin of hepatitis-related ICCs. Deleterious germline mutations of cancer-predisposing genes were detected in 11% of patients with BTC. BTCs have distinct genetic features including somatic events and germline predisposition

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: 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

Sufficient condition for locally unidentifiable edge weights from any single-state trajectory in networked linear systems

In this study, we analyse the local identifiability of parameters in linear systems whose state matrix is given by a graph Laplacian. Graph Laplacian is a matrix given by a graph and the weights of its edges, where the weights represent the parameters in those systems. There are cases in which parameter estimation has to be conducted with a single trajectory data. In this case, detecting whether the parameter is locally unidentifiable (non-locally identifiable (LI)) from a single-state trajectory a priori is important. This is because we need conditions to avoid estimating non-LI parameters. Therefore, we address a problem to find the condition which implies that the parameter is non-LI from any single-state trajectory. Then, we obtain a sufficient condition for the parameter to be non-LI from any single-state trajectory. The condition is given based on the number of vertices and edges of the graph and the number of distinct eigenvalues of the graph Laplacian. This paper also presents an example that satisfies the condition

Performance Limitation of Group Testing in Network Failure Detection

In a network system, there inevitably be a few connection failures at nodes, such as delay. Once a failure occurs, the network administrator must detect failure sources as soon as possible to maintain communication over the network. Group testing is a method for detecting failure nodes in networks using a small number of measurements, provided that the measurement matrix is constructed appropriately. A promising method for constructing measurement matrices is given by the binary correlation matrices. This study analyzes the performance limitation of group testing based on the binary correlation measurement matrix. We derive the upper and lower bounds of the minimum number of measurements needed for network detection. Moreover, we propose a sufficient condition of network topology, under which the failure vertices in the network can be detected with optimal performance, and we also provide a detection scheme with guaranteed exactness for the network. Numerical example indicates that for the network that satisfies the proposed sufficient condition, the administrator can exactly detect the failure vertices with optimal performance by using our proposed detection scheme

Consensus Control of Multi-Hopping-Rover Systems: Convergence Analysis

A hopping rover is a mobile robot developed for exploring low-gravity planets. The movement is based on hopping motion for moving on rough ground in low gravity. For efficient exploration, it is desirable to construct a cooperative system with multiple rovers. Such a system is called here the multi-hopping-rover systems. This paper addresses a consensus control problem for the multi-hopping-rover systems, where the hopping rovers involve uncertain dynamics caused by hopping motion. By representing the dynamics by a stochastic model and focusing on the dynamics of the disagreement, we present a condition on the control gain so that the system converges to consensus in a mean-square sense. The result is demonstrated by numerical simulation