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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. [ABSTRACT FROM AUTHOR]

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. Methods: A multidimensional assessment of MF incorporating radiological, surgical and histological parameters was performed in a prospective cohort of 34 patients with SINENs who underwent primary resection. Pre-operative blood samples were collected in 20 cases to evaluate a set of five profibrotic circulating transcripts—the "fibrosome"—that is included as an "omic" component of the NETest. Results: There was a significant correlation between radiological and surgical assessments of MF (p < 0.05). However, there were several cases of image-negative MF. The NETest-fibrosome demonstrated an accuracy of 100% for the detection of microscopic MF. Conclusions: The detection of MF by radiological criteria has limitations. The NETest-fibrosome is a promising biomarker for fibrosis detection and further validation of these results would be needed in larger, multicentre studies. [ABSTRACT FROM AUTHOR]

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. Methods: We assessed consecutive patients with biopsy‐proven NAFLD from three European centres. Clinical and laboratory data were collected at baseline and at the time of the last clinical follow‐up or death. CPA was performed at two different objective magnifications, whole biopsy macro and ×4 objective magnification, named standard (SM) and high (HM) magnification respectively. The correlation between CPA and liver stiffness was assessed in a sub‐group of patients. Results: Of 437 patients, 32 (7.3%) decompensated and/or died from liver‐related causes during a median follow‐up of 103 months. CPA correlated with liver stiffness and liver fibrosis stage across the whole spectrum of fibrosis. HM CPA was significantly higher than SM CPA in stages F0‐F3 but similar in cirrhosis, reflecting a higher ability to capture pericellular/perisinusoidal fibrosis at early stages. Age at baseline (HR: 1.04, 95% CI: 1.01‐1.08), HM CPA (HR: 1.04 per 1% increase, 95% CI: 1.01‐1.08) and presence of advanced fibrosis (HR: 15.4, 95% CI: 5.02‐47.84) were independent predictors of liver‐related clinical outcomes at standard and competing risk multivariate Cox‐regression analysis. Conclusions: CPA accurately measures fibrosis and is an independent predictor of clinical outcomes in NAFLD; hence it merits further evaluation as a surrogate endpoint in clinical trials. [ABSTRACT FROM AUTHOR]

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.Methods: Blood from patients with metastatic bronchial, midgut or pancreatic NET (pNET) was analysed by CellSearch. CXCR4 immunohistochemistry was performed on matched formalin-fixed paraffin-embedded (FFPE) samples.Results: Two hundred and fifty-four patients were recruited with 121 midgut and 119 pNETs, of which 51 and 36% had detectable CTCs, respectively. Bone metastases were reported in 30% of midgut and 23% of pNET patients and were significantly associated with CTC presence (p = 0.003 and p < 0.0001). In a subgroup of 40 patients, 85% patients with CTCs had CTCs positive for CXCR4 expression. The proportion of CXCR4-positive CTCs in patients with bone metastases was 56% compared to 35% in those without (p = 0.18) it. Staining for CXCR4 on matched FFPE tissue showed a trend towards a correlation with CXCR4 expression on CTCs (p = 0.08).Conclusions: CTC presence is associated with bone metastases in NETs. CXCR4 may be involved in CTC osteotropism and present a therapeutic target to reduce skeletal morbidity. [ABSTRACT FROM AUTHOR]

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 followup, 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 (0.1 mg/kg divided dose), azathioprine (1 mg/kg) and prednisolone (20 mg), the last tailing off to zero by 6 months. Both groups had serial transjugular biopsies with hepatic venous pressure gradient (HVPG) measurement. Time to reach Ishak stage 4 was the predetermined endpoint. CPA was measured in all biopsies. Factors associated with HCV recurrence were evaluated. Clinical decompensation was the first occurrence of ascites/hydrothorax, variceal bleeding or encephalopathy. Results No significant preoperative, peri-operative or postoperative differences between groups were found. During 96 months median follow-up, stage 4 fibrosis was reached in 19 MT/11 TT with slower fibrosis progression in TT ( p=0.009). CPA at last biopsy was 12% in MT and 8% in TT patients ( p=0.004). 14 MT/ three TT patients reached HVPG=10 mm Hg (p=0.002); 10 MT/three TT patients, decompensated. Multivariately, allocated MT ( p=0.047, OR 3.23, 95% CI 1.01 to 10.3) was independently associated with decompensation: 14 MT/ seven TT died, and five MT/ four TT were retransplanted. Conclusions Long term immunosuppression with tacrolimus, azathioprine and short term prednisolone in HCV cirrhosis recipients resulted in slower progression to severe fibrosis assessed by Ishak stage and CPA, less portal hypertension and decompensation, compared with tacrolimus alone. [ABSTRACT FROM AUTHOR]