The pan-cancer analysis of whole genomes The expansion of whole-genome sequencing studies from individual ICGC and TCGA working groups presented the opportunity to undertake a meta-analysis of genomic features across tumour types. To achieve this, the PCAWG Consortium was established. A Technical Working Group implemented the informatics analyses by aggregating the raw sequencing data from different working groups that studied individual tumour types, aligning the sequences to the human genome and delivering a set of high-quality somatic mutation calls for downstream analysis (Extended Data Fig. 1). Given the recent meta-analysis

A non-smooth tumor margin in the hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI is useful to predict MPVI, IM, and early recurrence of HCC after hepatectomy.

Background Cholangiolocellular carcinoma (CoCC) has distinct pathological characteristics, and CoCC is considered to originate from hepatic progenitor or stem cells. However, the surgical outcome of CoCC has not been clarified in detail.MethodsWe retrospectively studied 275 patients with intrahepatic cholangiocarcinoma (ICC) who underwent hepatectomy between 1990 and 2011. Surgical outcomes were compared between 29 patients with CoCC and 130 patients with mass-forming (MF) type ICC since all patients with CoCC showed MF type on macroscopic findings.ResultsThe number of patients with chronic liver disease was significantly higher in the CoCC group than in the ICC group. The number of patients with abnormal levels of CA19-9 was significantly lower in the CoCC group than in the ICC group. Portal vein invasion and intrahepatic metastasis were significantly lower in patients with CoCC group than in the ICC group. In the CoCC group, 15 of 28 patients survived for more than 5 years after curative surgery whereas 15 of 102 patients with ICC survived for more than 5 years after curative surgery. The 5-year survival rate was significantly higher in patients with CoCC (75 %) than in patients with ICC (33 %, p = 0.0005). Multivariate analysis showed CoCC, absence of portal vein invasion or hepatic vein invasion, and absence of intrahepatic metastasis to be significant independent prognostic factors for overall survival in patients with MF-type ICC and CoCC.ConclusionsCoCC is rare, but patients with CoCC had special characteristics with favorable long-term survival due to its less invasive histopathologic characteristics.

Cancers require telomere maintenance mechanisms for unlimited replicative potential. They achieve this through TERT activation or alternative telomere lengthening associated with ATRX or DAXX loss. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, we dissect whole-genome sequencing data of over 2500 matched tumor-control samples from 36 different tumor types aggregated within the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium to characterize the genomic footprints of these mechanisms. While the telomere content of tumors with ATRX or DAXX mutations (ATRX/DAXX trunc) is increased, tumors with TERT modifications show a moderate decrease of telomere content. One quarter of all tumor samples contain somatic integrations of telomeric sequences into non-telomeric DNA. This fraction is increased to 80% prevalence in ATRX/DAXX trunc tumors, which carry an aberrant telomere variant repeat (TVR) distribution as another genomic marker. The latter feature includes enrichment or depletion of the previously undescribed singleton TVRs TTCGGG and TTTGGG, respectively. Our systematic analysis provides new insight into the recurrent genomic alterations associated with telomere maintenance mechanisms in cancer.

Background Recently, the Liver Cancer Study Group of Japan (LCSGJ) staging system for intrahepatic cholangiocarcinoma (ICC) was followed by a proposal of the American Committee on Cancer (AJCC)/International Union Against Cancer (UICC) system. The present study aimed to assess the accuracy of both systems to predict survival after curative resection for mass-forming ICC and to establish a new staging system based on survival analysis results. The present study was conducted as a project study of the Japanese Society of Hepato-Biliary-Pancreatic Surgery. Methods Clinical data from 233 patients who underwent curative resection for mass-forming ICC were retrospectively reviewed. Survival analysis was performed to identify predictors of postoperative outcomes, and a new staging system was established. The survival stratification of our proposed system was compared with two previous staging systems.Results A N0M0 cohort analysis demonstrated that tumor size, tumor number, and vascular invasion were independently associated with survival after curative resection for mass-forming ICC, whereas serosal and periductal invasion were not. Of patients with nodal metastases, patients with T4 tumor had significantly lower overall survival rate than patients with T1, T2, or T3 tumor. Thus, we proposed a new staging system as follows: serosal invasion was excluded from the LCSGJ T categories, and patients with nodal metastases were divided into stage IVA or IVB according to T classification. The new system better stratified survival after curative resection for mass-forming ICC than the two previous systems.

MF type ICC with marked enhancement within the tumor on arterial CT scans showed a favorable surgical outcome due to its less invasive histopathologic characteristics in patients with MF type ICC.

The Glissonean pedicle approach in liver surgery provides new knowledge of the surgical anatomy of the liver and advances the technique of liver surgery. The Glissonean pedicles are wrapped by a connective tissue referred to as the Glisson’s capsule and include the hepatic artery, portal vein and bile duct. The Glissonean pedicles can be approached intrahepatically or extrahepatically. The extrahepatic approach at the hepatic hilus was referred to as the extra-fascial access by Couinaud. In summary, the secondary Glissonean pedicles are encircled and ligated at the hepatic hilus without liver dissection. The angle of approach should be over the hilar plate so that the surgeon does not have to consider any variations in the arteries or bile ducts. The tertiary branches can be approached through the hepatic hilus extrahepatically or intrahepatically on the border between the sections which are fed by the secondary Glissonean pedicles. This procedure is suitable for liver cancer without hilar invasion, particularly for hepatocellular carcinoma (HCC). Patients with HCC usually have liver dysfunction and HCC easily invades the peripheral portal vein; therefore, patients with HCC should only undergo small anatomical hepatectomies such as sectionectomy or segmentectomy. Any anatomical hepatectomy can be performed using this technique which allows simple, safe and easy liver resection. Liver surgeons should, therefore, know the fundamental concept of the Glissonean pedicle transection method.Electronic supplementary materialThe online version of this article (doi:10.1007/s00534-011-0443-0) contains supplementary material, which is available to authorized users.

Recent studies applying high-throughput sequencing technologies have identified several recurrently mutated genes and pathways in multiple cancer genomes. However, transcriptional consequences from these genomic alterations in cancer genome remain unclear. In this study, we performed integrated and comparative analyses of whole genomes and transcriptomes of 22 hepatitis B virus (HBV)-related hepatocellular carcinomas (HCCs) and their matched controls. Comparison of whole genome sequence (WGS) and RNA-Seq revealed much evidence that various types of genomic mutations triggered diverse transcriptional changes. Not only splice-site mutations, but also silent mutations in coding regions, deep intronic mutations and structural changes caused splicing aberrations. HBV integrations generated diverse patterns of virus-human fusion transcripts depending on affected gene, such as TERT, CDK15, FN1 and MLL4. Structural variations could drive over-expression of genes such as WNT ligands, with/without creating gene fusions. Furthermore, by taking account of genomic mutations causing transcriptional aberrations, we could improve the sensitivity of deleterious mutation detection in known cancer driver genes (TP53, AXIN1, ARID2, RPS6KA3), and identified recurrent disruptions in putative cancer driver genes such as HNF4A, CPS1, TSC1 and THRAP3 in HCCs. These findings indicate genomic alterations in cancer genome have diverse transcriptomic effects, and integrated analysis of WGS and RNA-Seq can facilitate the interpretation of a large number of genomic alterations detected in cancer genome.