Concomitant Heterotopic Pancreas and Endometriosis as a Rare Cause of Ileo-Ileal Intussusception in a Young Woman with Spina Bifida: Case Report and Literature Review.

INTRODUCTION: Isolated heterotopic pancreas (HP) as the primary cause of bowel intussusception is extremely rare. We report a case of a 33-year-old female patient with spina bifida admitted to the Emergency Surgical Department for ileal intussusception due to the presence of heterotopic pancreas associated with endometriosis. AREAS COVERED: Symptomatic ileal intussusception for ectopic pancreas is usually associated with overt gastrointestinal blood loss (predominantly melena), abdominal pain, vomiting, and weight loss. Treatment is universally surgical. EXPERT COMMENTARY: Isolated heterotopic pancreas is a rare condition; it should be considered in the differential diagnosis of bowel intussusception.

Membrane human equilibrative nucleoside transporter 1 is associated with a high proliferation rate and worse survival in resected intrahepatic cholangiocarcinoma patients not receiving adjuvant treatments.

Human equilibrative nucleoside transporter 1 (hENT-1) is a membrane nucleoside transporter mediating the intracellular uptake of nucleosides and their analogues. hENT-1 was recently reported to have a predictive role in intrahepatic cholangiocarcinoma (iCC) patients receiving adjuvant gemcitabine-based chemotherapy, but its biological and clinical significance in iCC remains unsettled. This study investigated the role of hENT-1 in regulating tumour growth and predicting the survival of 40 resected iCC patients not receiving adjuvant treatments. hENT-1 expression was found to be significantly higher in iCC than in the matched non-tumoural liver. Patients harbouring hENT-1 localised on the tumour cell membrane had a worse overall survival than membrane hENT-1-negative patients (median 21.2 months vs 30.3 months, p = 0.031), with an adjusted hazard ratio of 2.8 (95% confidence interval 1.01-7.76). Moreover, membrane hENT-1-positive patients had a higher percentage of Ki67-positive cells in tumour tissue than membrane hENT-1-negative patients (median 23% vs 5%, p < 0.0001). Functional analyses in iCC cell lines revealed that hENT-1 silencing inhibited cell proliferation and induced apoptosis in HUH-28 cells expressing hENT-1 on the cell membrane, but not in SNU-1079 cells expressing the transporter only in the cytoplasm. Overall, these findings suggest that membrane hENT-1 is involved in iCC proliferation and associated with worse survival in resected iCC patients. Further prospective studies on larger cohorts are required to confirm these results and better define the potential prognostic role of membrane hENT-1 in this setting of patients.

Metabolic Profile of Obeticholic Acid and Endogenous Bile Acids in Rats with Decompensated Liver Cirrhosis.

Obeticholic acid (OCA) is a semisynthetic bile acid (BA) analog and potent farnesoid X receptor agonist approved to treat cholestasis. We evaluated the biodistribution and metabolism of OCA administered to carbon tetrachloride-induced cirrhotic rats. This was to ascertain if plasma and hepatic concentrations of OCA are potentially more harmful than those of endogenous BAs. After administration of OCA (30 mg/kg), we used liquid chromatography-mass spectrometry to measure OCA, its metabolites, and BAs at different timepoints in various organs and fluids. Plasma and hepatic concentrations of OCA and BAs were higher in cirrhotic rats than in controls. OCA and endogenous BAs had similar metabolic pathways in cirrhotic rats, although OCA hepatic and intestinal clearance were lower than in controls. BAs' qualitative and quantitative compositions were not modified by a single administration of OCA. In all the matrices studied, OCA concentrations were significantly lower than those of endogenous BAs, potentially much more cytotoxic.

Biochemical and immunomorphological evaluation of hepatocyte growth factor and c-Met pathway in patients with critical limb ischemia.

OBJECTIVES: Hepatocyte growth factor (HGF), the c-Met receptor, and hypoxia-inducible factor (HIF) are crucial for regenerative processes including ischemic wound healing. The aims of the present study are (a) to analyze the tissue c-Met and HIF-1α expression in skin from patients with critical limb ischemia (CLI); (b) to compare the serum HGF levels of CLI and control subjects. METHODS: This is a prospective, controlled, single-center study. Thirty-seven patients were enrolled. A skin sample adjacent to the ischemic lesion was taken from 20 patients with CLI; skin samples were taken from the surgical wounds of 17 patients surgically treated for abdominal aortic aneurysm as healthy controls. Serum samples were taken in all cases. Samples were formalin fixed, paraffin embedded, and routinely processed. Tissue inflammation was histologically assessed. Immunohistochemistry was performed with antibodies against total c-Met receptor, activated Met (p-Met), and HIF-1α. RT-polymerase chain reaction was used to quantify HIF-1α mRNA. The enzyme-linked immunosorbent assay was performed to evaluate serum HGF levels. RESULTS: With immunohistochemistry, while total c-Met was unchanged, different patterns of p-Met positivity were observed between CLI and control cases (p < .001). In particular, CLI skin showed a total negativity or membrane positivity for p-Met (19/20 cases), while control skin mainly showed cytoplasmic positivity in the epidermal basal layer (16/17 cases). HIF-1α was diffusely lost in CLI, but HIF-1α mRNA was threefold higher than in controls. Finally, mean serum HGF levels were 590.5 pg/mL and 2380.0 pg/mL in CLI and control groups respectively (p < .001). CONCLUSIONS: In CLI patients a significant decrease in serum HGF levels, concomitant with a loss of skin HIF-1α stabilization and a lack of c-Met phosphorylation were seen, probably driving a decrease in wound-healing functions. The next hypothesis is that HGF application might reactivate the c-Met receptor, stabilizing the normal wound healing process.

Expanding the criteria of organ procurement from donors with prostate cancer: the application of the new Italian guidelines.

Prostate cancer (CaP) represents the most prevalent malignancy in men more than 60-year-old, posing a problem in organ procurement from elderly subjects. However, most of the currently diagnosed CaP are low-grade and intraprostatic, with low metastatic risk, and there is recent evidence that most patients are overdiagnosed. The Italian National guidelines about organ acceptance from neoplastic donors changed in March 2005, extending the pool of potential candidates with CaP and introducing the function of a second opinion expert. Between 2001 and February 2005, 40 candidate donors with total PSA>/=10 and/or positive digital rectal examination underwent histopathological analysis of the prostate: 15 (37.5%) donors harboured CaP, and 25 (62%) were judged at 'standard risk'. After the introduction of the new guidelines in 2005, the second opinion expert judged at 'standard risk' 48 of 65 donors, while 17 of 65 needed histopathological analysis. Four (6.2%) donors harboured CaP, and 61 (94%) where judged at 'standard risk', with a significant increase of donated and actually transplanted organs. The application of the new guidelines and the introduction of a second opinion expert allowed a significant extension of the 'standard risk' category also to CaP patients, decreasing the histopathological examinations and expanding the donor pool.

Assessment of liver fibrosis in transplant recipients with recurrent HCV infection: usefulness of transient elastography.

BACKGROUND: Progression of recurrent hepatitis C is accelerated in liver transplant recipients, leading to special need of non-invasive validated methods to estimate liver fibrosis. AIM: To assess the efficacy of liver stiffness measurement by transient elastography (Fibroscan) and serum parameters in predicting fibrosis stage in HCV-infected transplant recipients. METHODS: The correlation between liver fibrosis, assessed at liver histology on bioptic specimens obtained for clinical indications, and stiffness or clinico-serological indexes (Benlloch, APRI, Forns, Fibrotest and Doppler resistance index), was investigated in transplant recipients with recurrence of HCV chronic hepatitis. A total of 56 patients (of which 36 with all clinico-serological indexes), presenting with the following METAVIR fibrosis stage F1=38, F2=9, F3=8, F4=1, were enrolled in the study population. Differences between fibrosis stages were calculated by non-parametric analysis. The best cut-off for identifying significant fibrosis (F2-F4) was assessed by ROC curve analysis. RESULTS: Stiffness (median and range) was 7.7 KPa (range 4.2-13.9) in F1 and 17.0KPa (range 6.8-36.3) in >or=F2 (p<0.001). A stiffness cut-off of 10.1 KPa revealed 94% Sensitivity, 89% Specificity, 81% PPV and 94% NPV in differentiating F1 from F2-F4. The area under the receiver operator curve in the assessment of fibrosis was significantly higher for Liver stiffness (AUROC 0.943) than for any of the other non-invasive indexes (AUROCs ranging 0.591-0.815). CONCLUSIONS: Transient elastography of the liver provides good accuracy in identifying patients with significant fibrosis and performs better than non-invasive indexes based on clinico-serological parameters in transplant recipients.