The rs4374383 AA genotype, associated with lower intrahepatic expression of MERTK, is protective against F2-F4 fibrosis in patients with NAFLD. The mechanism may involve modulation of HSC activation.

Hepatocellular carcinoma (HCC) is a major health problem with a high incidence and mortality all over the world. Natural history of HCC is severe and extremely variable, and prognostic factors influencing outcomes are incompletely defined. Over time, many staging and scoring systems have been proposed for the classification and prognosis of patients with HCC. Currently, the non-ideal predictive performance of existing prognostic systems is secondary to their inherent limitations, as well as to a non-universal reproducibility and transportability of the results in different populations. New serological and histological markers are still under evaluation with promising results, but they require further evaluation and external validation. The aim of this review is to highlight the main tools for assessing the prognosis of HCC and the main concerns, pitfalls and warnings regarding its staging systems currently in use.

This study, despite being retrospective, indicates that both cyclosporine and infliximab are effective in avoiding a colectomy in steroid-refractory UC patients. During the follow-up the risk of a colectomy is higher in patients treated with cyclosporine than with infliximab.

Vulvar malignancies are important tumors of the female reproductive system. They represent a serious health issue with an incidence between 2 and 7 per 100,000 and year. We provide a review about most important cancer entities, i.e., melanoma, squamous cell carcinoma, basal cell carcinoma, neuroendocrine cancer, and skin adnexal malignancies.Squamous cell carcinoma is the most common vulvar malignancy that can develop from vulvar intraepithelial neoplasia or de novo. Basal cell carcinoma represents only 2% of all vulvar cancers. Melanoma of the vulva exists in two major types-superficial spreading and acral lentiginous. A special feature is the occurrence of multiple vulvar melanomas. Of the adnexal cancer types Paget's disease and carcinoma are seen more frequently than other adnexal malignancies. The dermatologist should be aware of this problem, since he might be the first to be consulted by patients for vulvar disease. Treatment should be interdisciplinary in close association to gynecologists, oncologists, and radiologists.

We describe glycoprotein (GP) Ib as a mediator of adhesion to fibronectin, specifically in flow. A monoclonal antibody (MoAb) directed to the von Willebrand factor (vWF)-binding site on this receptor or the absence of this receptor on the platelet membrane, in the case of a patient with the Bernard-Soulier syndrome, reduced platelet coverage to fibronectin to approximately 30% of the control value. A MoAb directed to the GP Ib-binding site on vWF showed a similar effect. With washed platelets in the absence of plasma vWF, the inhibitory effect of the anti-GP Ib antibody was the same as with whole blood. No inhibition with the anti-GP Ib antibody was observed when we used blood from patients with severe von Willebrand disease (vWD) or from a patient with vWD type I (platelet low). Addition of vWF to vWD blood resulted in restoration of adhesion. Immunoelectron microscopy on platelets adhering to fibronectin showed that GP Ib was homogeneously distributed over the entire surface of the platelet. vWF was present at the central zone and the edges of the platelet and at the basal interface between the platelet and the fibronectin surface. No direct binding of vWF to fibronectin could be demonstrated. These data indicate that GP Ib-mediated adhesion to fibronectin fully depends on vWF and that normal levels of plasma or platelet vWF are sufficient for optimal adhesion to fibronectin. The data suggest that the presence of platelets during perfusion is a prerequisite for vWF to support platelet adhesion to fibronectin.

The natural history of Crohn's Disease and ulcerative colitis is characterized by repeated episodes of inflammation and ulceration of the bowel. This results in complications implying a worse quality of life and significant healthcare costs, due to hospitalization, surgery and an escalation of therapy. The main goal of the therapy in inflammatory bowel disease is to achieve and maintain disease remission, with an improved health-related quality of life, less hospitalization, and less surgery. The concept of remission has changed in the recent years. In fact the concept of clinical remission, where only the patients' symptoms are in remission, has been replaced by the new concept of deep remission. This implies not only sustained clinical remission but also complete mucosal healing, with the normalization of serological activity indexes. Mucosal healing, rarely achieved with traditional drugs, can now be achieved and maintained by means of biological drugs. Current evidence suggests that the achievement of mucosal healing might significantly change the natural course of inflammatory bowel diseases and should represent an objective end point of future therapeutic trials, particularly for colonic diseases.

a b s t r a c tPrimary Neuroendocrine Tumours (NETs) of the gallbladder are rare. Among all NETs of the gallbladder, large cell neuroendocrine carcinoma (LCNEC) is exceedingly rare. In most of the cases LCNECs are combined with other histological components. We reviewed clinical presentation and management of all patients with "pure" LCNEC from published literature since the first case was published in 2000, as well as one patient from our experience. Only 7 cases of "pure" LCNEC has been described in the last 15 years, our case is the eighth. The diagnosis of gallbladder NETs is rarely made preoperatively since the presentation generally consists of non-specific symptoms including upper abdominal pain, discomfort, jaundice, weight loss. The majority of patients are identified incidentally at the time of cholecystectomy for cholelithiasis. It is not possible to differentiate preoperatively between gallbladder adenocarcinoma and gallbladder neuroendocrine carcinoma (NEC) with imaging techniques. The only curative therapeutic modality for LCNECs is a complete en bloc surgical resection, including regional lymph node clearances and hepatic lobectomy, but only in patients without multiple metastasis. LCNECs benefit from an aggressive surgical resection in combination with chemotherapy, if resectability is possible. If the tumour is non-resectable, the primary management is therefore medical and not surgical. All patients with LCNEC presented a poor prognosis with a median survival of 10 months after the initial diagnosis. Only in five patients (62.5%) a wide surgical excision was performed, while in the other cases the tumour was non-resectable or multiple liver metastases were present at diagnosis.

BackgroundRadio-frequency ablation (RFA) has been employed in the treatment of Barcelona Clinic Liver Cancer (BCLC) early stage hepatocellular carcinoma (HCC) as curative treatments.AimTo assess the effectiveness and the safety of RFA in patients with early HCC and compensated cirrhosis.MethodsA cohort of 151 consecutive patients with early stage HCC (122 Child-Pugh class A and 29 class B patients) treated with RFA were enrolled. Clinical, laboratory and radiological follow-up data were collected from the time of first RFA.A single lesion was observed in 113/151 (74.8%), two lesions in 32/151 (21.2%), and three lesions in 6/151 (4%) of patients.ResultsThe overall survival rates were 94%, 80%, 64%, 49%, and 41% at 12, 24, 36, 48 and 60 months, respectively. Complete response (CR) at 1 month (p<0.0001) and serum albumin levels (p = 0.0004) were the only variables indipendently linked to survival by multivariate Cox model. By multivariate analysis, tumor size (p = 0.01) is the only variable associated with an increased likehood of CR.The proportion of major complications after treatment was 4%.ConclusionsRFA is safe and effective for managing HCC with cirrhosis, especially for patients with HCC ≤3 cm and higher baseline albumin levels. Complete response after RFA significantly increases survival.