Neuroendocrine tumours and pregnancy: Real-world data from an European Neuroendocrine Tumour Centre of Excellence.

Neuroendocrine neoplasms (NENs) arise from the diffuse endocrine system and have been considered to be rare. However, the incidence and prevalence of these tumours have increased in recent years, and they are being seen in younger patients including women in the reproductive age group. Due to the paucity of data, diagnostic and therapeutic strategies in managing such tumours during pregnancy can be challenging to both treating physicians and patients.

Duodenal neuroendocrine neoplasms with unexpectedly aggressive behaviour: Challenging the "watch and wait" approach.

The incidence of duodenal neuroendocrine neoplasms has risen over the past decades as a result of the wide availability of endoscopy and associated expertise. Although it is considered that tumour size greater than 10 mm, higher tumour grade and/or location in relation to the ampulla of Vater represent the main risk factors for local or distant metastases, we describe two cases of well differentiated grade 1 and grade 2 neuroendocrine tumours, which measured < 10 mm at the time of diagnosis but had an aggressive course during follow-up. Furthermore, we also summarise the available therapeutic strategies for the management of small, low grade, non-functioning, non-ampullary duodenal neuroendocrine neoplasms.

Clinicopathological correlations of mesenteric fibrosis and evaluation of a novel biomarker for fibrosis detection in small bowel neuroendocrine neoplasms.

Purpose: Mesenteric fibrosis (MF) in small intestinal neuroendocrine neoplasms (SINENs) is often associated with significant morbidity and mortality. The detection of MF is usually based on radiological criteria, but no previous studies have attempted a prospective, multidimensional assessment of mesenteric desmoplasia to determine the accuracy of radiological measurements. There is also a lack of non-invasive biomarkers for the detection of image-negative MF.

Collagen proportionate area is an independent predictor of long-term outcome in patients with non-alcoholic fatty liver disease.

Background: Collagen proportionate area (CPA) measurement is a technique that quantifies fibrous tissue in liver biopsies by measuring the amount of collagen deposition as a proportion of the total biopsy area. CPA predicts clinical outcomes in patients with HCV and can sub-classify cirrhosis.

Aim: To test the ability of CPA to quantify fibrosis and predict clinical outcomes in patients with NAFLD.

Circulating tumour cells and their association with bone metastases in patients with neuroendocrine tumours.

Background: Bone metastases are associated with a worse outcome in patients with neuroendocrine tumours (NETs). Tumour overexpression of C-X-C chemokine receptor 4 (CXCR4) appears predictive of skeletal involvement. We investigated the role of circulating tumour cells (CTCs) and CXCR4 expression on CTCs as potential predictors of skeleton invasion.

MAIT cells are chronically activated in patients with autoimmune liver disease and promote profibrogenic hepatic stellate cell activation.

Unlabelled: Autoimmune liver diseases (AILDs) are chronic liver pathologies characterized by fibrosis and cirrhosis due to immune-mediated liver damage. In this study, we addressed the question whether mucosal-associated invariant T (MAIT) cells, innate-like T cells, are functionally altered in patients with AILD and whether MAIT cells can promote liver fibrosis through activation of hepatic stellate cells (HSCs). We analyzed the phenotype and function of MAIT cells from AILD patients and healthy controls by multicolor flow cytometry and investigated the interaction between human MAIT cells and primary human hepatic stellate cells (hHSCs).

IL-2 tissue-resident T cells in the human liver: Sentinels for hepatotropic infection.

The liver provides a tolerogenic immune niche exploited by several highly prevalent pathogens as well as by primary and metastatic tumors. We have sampled healthy and hepatitis B virus (HBV)-infected human livers to probe for a subset of T cells specialized to overcome local constraints and mediate immunity. We characterize a population of T-betEomesBlimp-1Hobit T cells found within the intrahepatic but not the circulating memory CD8 T cell pool expressing liver-homing/retention markers (CD69CD103 CXCR6CXCR3).

Prognostic Impact of Novel Molecular Subtypes of Small Intestinal Neuroendocrine Tumor.

Purpose: Small intestinal neuroendocrine tumors (SINET) are the commonest malignancy of the small intestine; however, underlying pathogenic mechanisms remain poorly characterized. Whole-genome and -exome sequencing has demonstrated that SINETs are mutationally quiet, with the most frequent known mutation in the cyclin-dependent kinase inhibitor 1B gene (CDKN1B) occurring in only ∼8% of tumors, suggesting that alternative mechanisms may drive tumorigenesis. The aim of this study is to perform genome-wide molecular profiling of SINETs in order to identify pathogenic drivers based on molecular profiling.

Goblet cell appendiceal tumors--management dilemmas and long-term outcomes.

Background: Appendiceal Goblet cell tumors (GCTs) are clinically more aggressive, and have a worse outcome than midgut neuroendocrine tumors (mNETs). Guidelines for management of GCTs are limited.

Methods: A retrospective case-study analysis was performed in patients with a diagnosis of GCT, confirmed on histological review.

Inflammation-based scores do not predict post-transplant recurrence of hepatocellular carcinoma in patients within Milan criteria.

Increased preoperative inflammation scores, such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and inflammation-based index (IBI) have been related to post-transplant HCC recurrence. We evaluated the association between inflammation-based scores (NLR, PLR, IBI) and post-LT HCC recurrence as well as tumor necrosis after transarterial embolization. 150 consecutive patients who underwent transplantation for HCC within the Milan criteria between 1996 and 2010 were included; data regarding inflammatory markers, patient and tumor characteristics were analyzed.

The use of guideline images to improve histological estimation of hepatic steatosis.

Background & Aims: Guideline images of specific fat proportionate area (FPA) percentages have recently been published to aid the histological assessment of liver steatosis as subjective estimates of FPA are usually overestimated. To assess, (i) the effect of guideline images on accuracy and concordance of estimated FPA (eFPA), (ii) experience of steatosis grading systems on eFPA, (iii) the effect of magnification on assessment of FPA (iv) and produce a range of guideline images at x4 objective magnification (OM).

Methods: Two circulations of sample images (C1 and C2) were circulated to UK liver external quality assessment histopathology scheme members who were asked to independently evaluate steatosis.

Capecitabine and streptozocin ± cisplatin in advanced gastroenteropancreatic neuroendocrine tumours.

Background: Cytotoxic chemotherapy is widely used for advanced, unresectable pancreatic and other gastrointestinal foregut neuroendocrine tumours (NETs) and the most commonly used regimen combines 5-fluorouracil with streptozocin. The NET01 trial was designed to investigate whether capecitabine combined with streptozocin was an acceptable regimen with or without adding cisplatin.

Methods: Patients with advanced, unresectable NETs of pancreatic, gastrointestinal foregut or unknown primary site were randomised to receive three-weekly capecitabine (Cap) 625 mg/m(2) twice daily orally, streptozocin (Strep) 1.

Reduced fibrosis in recurrent HCV with tacrolimus, azathioprine and steroids versus tacrolimus: randomised trial long term outcomes.

Objective: Early results of a randomised trial showed reduced fibrosis due to recurrent HCV hepatitis with tacrolimus triple therapy (TT) versus monotherapy (MT) following transplantation for HCV cirrhosis. We evaluated the clinical outcomes after a median 8 years of follow-up, including differences in fibrosis assessed by collagen proportionate area (CPA).

Design: 103 consecutive liver transplant recipients with HCV cirrhosis receiving cadaveric grafts were randomised to tacrolimus MT (n=54) or TT (n=49) with daily tacrolimus (0.

A case of medullary sponge kidney (Cacchi-Ricci disease) mimicking a renal mass.

Medullary sponge kidney (MSK) is an uncommon benign congenital disorder, generally asymptomatic. In symptomatic patients the diagnosis is usually made by excretory urography performed in the most frequent complications such as renal stones, urinary tract infections and haematuria. Excretory urography can be very characteristic, showing cystic collections of ectatic collecting ducts like "bunches of grapes" or "bouquet of flowers".