The incidence of non-functioning pancreatic neuroendocrine neoplasms (NF-PanNENs) has increased recently¹. Traditionally, surgery has been the treatment of choice for localized NF-PanNENs, although evidence has emerged that active surveillance could be advocated for most asymptomatic tumours no larger than 2 cm^2–7. However, the practice of active surveillance varies considerably and, contrary to current recommendations^8–10, many patients still undergo surgical resection^11–13.

Gallbladder cancer (GBC) is an aggressive gastrointestinal malignancy with no approved targeted therapy. Here, we analyze exomes (n = 160), transcriptomes (n = 115), and low pass whole genomes (n = 146) from 167 gallbladder cancers (GBCs) from patients in Korea, India and Chile. In addition, we also sequence samples from 39 GBC high-risk patients and detect evidence of early cancer-related genomic lesions. Among the several significantly mutated genes not previously linked to GBC are ETS domain genes ELF3 and EHF, CTNNB1, APC, NSD1, KAT8, STK11 and NFE2L2. A majority of ELF3 alterations are frame-shift mutations that result in several cancer-specific neoantigens that activate T-cells indicating that they are cancer vaccine candidates. In addition, we identify recurrent alterations in KEAP1/NFE2L2 and WNT pathway in GBC. Taken together, these define multiple targetable therapeutic interventions opportunities for GBC treatment and management.

Background In gallbladder cancer, stage T2 is subdivided by tumour location into lesions on the peritoneal side (T2a) or hepatic side (T2b). For tumours on the peritoneal side (T2a), it has been suggested that liver resection may be omitted without compromising the prognosis. However, data to validate this argument are lacking. This study aimed to investigate the prognostic value of tumour location in T2 gallbladder cancer, and to clarify the adequate extent of surgical resection. Methods Clinical data from patients who underwent surgery for gallbladder cancer were collected from 14 hospitals in Korea, Japan, Chile and the USA. Survival and risk factor analyses were conducted. Results Data from 937 patients were available for evaluation. The overall 5‐year disease‐free survival rate was 70·6 per cent, 74·5 per cent for those with T2a and 65·5 per cent among those with T2b tumours (P = 0·028). Regarding liver resection, extended cholecystectomy was associated with a better 5‐year disease‐free survival rate than simple cholecystectomy (73·0 versus 61·5 per cent; P = 0·012). The 5‐year disease‐free survival rate was marginally better for extended than simple cholecystectomy in both T2a (76·5 versus 66·1 per cent; P = 0·094) and T2b (68·2 versus 56·2 per cent; P = 0·084) disease. Five‐year disease‐free survival rates were similar for extended cholecystectomies including liver wedge resection versus segment IVb/V segmentectomy (74·1 versus 71·5 per cent; P = 0·720). In multivariable analysis, independent risk factors for recurrence were presence of symptoms (hazard ratio (HR) 1·52; P = 0·002), R1 resection (HR 1·96; P = 0·004) and N1/N2 status (N1: HR 3·40, P < 0·001; N2: HR 9·56, P < 0·001). Among recurrences, 70·8 per cent were metastatic. Conclusion Tumour location was not an independent prognostic factor in T2 gallbladder cancer. Extended cholecystectomy was marginally superior to simple cholecystectomy. A radical operation should include liver resection and adequate node dissection.

A single tumor marker has a low diagnostic value in pancreatic cancer. Combinations of multiple biomarkers and unique analysis algorithms can be applied to overcome these limitations. This study sought to develop diagnostic algorithms using multiple biomarker panels and to validate their performance in the diagnosis of pancreatic ductal adenocarcinoma (PDAC). We used blood samples from 180 PDAC patients and 573 healthy controls. Candidate markers consisted of 11 markers that are commonly expressed in various cancers and which have previously demonstrated increased expression in pancreatic cancer. Samples were divided into training and validation sets. Five linear or non-linear classification methods were used to determine the optimal model. Differences were identified in 10 out of the 11 markers tested. We identified 2047 combinations, all of which were applied to 5 separate algorithms. The new biomarker combination consisted of 6 markers (ApoA1, CA125, CA19-9, CEA, ApoA2, and TTR). The area under the curve, specificity, and sensitivity were 0.992, 95%, and 96%, respectively, in the training set. Meanwhile, the measures were 0.993, 96%, and 93% in the validation set. This study demonstrated the utility of multiple biomarker combinations in the early detection of PDAC. A diagnostic panel of 6 biomarkers was developed and validated. These algorithms will assist in the early diagnosis of PDAC.

Novel biomarkers for early diagnosis of pancreatic cancer (PC) are necessary to improve prognosis. We aimed to discover candidate biomarkers by identifying compositional differences of microbiome between patients with PC (n = 38) and healthy controls (n = 52), using microbial extracellular vesicles (EVs) acquired from blood samples. Composition analysis was performed using 16S rRNA gene analysis and bacteria-derived EVs. Statistically significant differences in microbial compositions were used to construct PC prediction models after propensity score matching analysis to reduce other possible biases. Between-group differences in microbial compositions were identified at the phylum and genus levels. At the phylum level, three species (Verrucomicrobia, Deferribacteres, and Bacteroidetes) were more abundant and one species (Actinobacteria) was less abundant in PC patients. At the genus level, four species (Stenotrophomonas, Sphingomonas, Propionibacterium, and Corynebacterium) were less abundant and six species (Ruminococcaceae UCG-014, Lachnospiraceae NK4A136 group, Akkermansia, Turicibacter, Ruminiclostridium, and Lachnospiraceae UCG-001) were more abundant in PC patients. Using the best combination of these microbiome markers, we constructed a PC prediction model that yielded a high area under the receiver operating characteristic curve (0.966 and 1.000, at the phylum and genus level, respectively). These microbiome markers, which altered microbial compositions, are therefore candidate biomarkers for early diagnosis of PC.