Increasing significance of tumor–stromal interaction in development and progression of cancer implies that signaling molecules in the tumor microenvironment (TME) might be the effective therapeutic targets for hepatocellular carcinoma (HCC). Here, the role of microRNA miR-199a-3p in the regulation of TME and development of HCC has been investigated by several in vitro and in vivo assays. Expression of miR-199a-3p was observed significantly low in HCC tissues and its overexpression remarkably inhibited in vivo tumor growth and metastasis to lung in NOD-SCID mice. In vitro restoration of miR-199a-3p expression either in endothelial cells (ECs) or in cancer cells (CACs) significantly diminished migration of ECs in co-culture assay. Again incubation of miR-199a-3p transfected ECs with either conditioned media (CM) of CACs or recombinant VEGF has reduced tube formation, in ECs and it was also dropped upon growth in CM of either anti-VEGF antibody-treated or miR-199a-3p-transfected CACs. In addition, bioinformatics and luciferase-reporter assays revealed that miR-199a-3p inhibited VEGF secretion from CACs and VEGFR1 and VEGFR2 expression on ECs and thus restricted cross talk between CACs and ECs. Again, restoration of miR-199a-3p in hepatic stellate cells (HSCs) reduced migration and invasion of CACs in co-culture assay, while it was enhanced by the overexpression of HGF suggesting miR-199a-3p has hindered HSC-CACs cross talk probably by inhibiting HGF and regulating matrix metalloproteinase MMP2, which were found as targets of miR-199a-3p subsequently by luciferase-reporter assay and gelatin zymography, respectively. Thus, these findings collectively highlight that miR-199a-3p restricts metastasis, invasion and angiogenesis in HCC and hence it may be considered as one of the powerful effective therapeutics for management of HCC patients.

Decompressive shunt surgery alone relieves biliary obstruction in the majority of patients with symptomatic PBP and facilitates endoscopic or surgical management in patients who require second-stage management of biliary obstruction.

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Objectives: The presentation of choledochal cysts (CDCs) is altered by complications such as acute severe cholangitis, hepatolithiasis, spontaneous perforation, portal hypertension, pancreatitis, malignancy of the biliary tract and previous surgery in the form of internal drainage of the cyst. The management and the outcome of such complicated cysts differ from that of an uncomplicated CDC. This presentation is an analysis of our experience with complicated CDCs. Patients and Methods: One hundred and forty-four patients with CDCs were managed at a tertiary level referral hospital in North India, between January 1989 and June 2004. Thirty-three (23%) CDCs were associated with complicating factors: severe cholangitis requiring a biliary drainage procedure prior to definitive operative procedure (n = 11), spontaneous perforation (n = 3), hepatolithiasis (n = 6), acute cholecystitis (n = 1), recurrent acute pancreatitis (n = 1), chronic pancreatitis (n = 1), gastric outlet obstruction (n = 1), portal hypertension (n = 6), biliary tract malignancy (n = 4) and previous internal drainage of the cyst (n = 5). Five patients had more than one complication. The management outcome of complicated CDCs was compared with that of uncomplicated CDCs. Results: Complicated CDCs were significantly more common with type IV-A anatomy. Endoscopic, percutaneous or external surgical biliary drainage procedure was performed in 14 complicated CDCs prior to cyst excision. Desired definitive surgical procedure could be performed in 26/33 (79%) patients with complicated CDCs as compared to 107/111 (96%) patients with uncomplicated CDCs. Four (12%) patients with complicated CDCs had early postoperative complications as compared to 9/111 (8%) patients with uncomplicated CDCs. During a median follow-up of 13 months (2 months to 8 years), 2 patients with complicated CDCs died due to advanced secondary biliary cirrhosis and advanced gall bladder cancer, respectively. Six patients reported complications. Of the 6 patients, 3 required reoperation for a strictured hepaticojejunostomy (n = 2) and hepatolithiasis (n = 1). In contrast, there was no disease-related mortality and only 1 out of 111 patients with uncomplicated cysts had a complication during follow-up. Conclusion: Complicated CDCs merit a carefully planned management strategy including percutaneous, endoscopic and surgical procedures. The management may have to be staged. The outcome depends on the nature of complication and the management strategy adopted.

Excision of the extrahepatic part of the cyst and drainage of the intrahepatic part by a wide hilar or subhilar anastomosis gave satisfactory results in the majority of patients with type IV-A choledochal cysts. Close long-term follow up of these patients is essential, because they are likely to present with complications related to the residual intrahepatic part of the disease.

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Living donor liver transplantation (LDLT) in obese patients raises concerns with regards to obtaining grafts of "adequate" graft-to-recipient weight ratio (GRWR) and the impact of obesity on the outcomes of LDLT. LDLT outcomes in patients weighing 100 kg were compared with those weighing <100 kg. Patients weighing 100 kg were divided into 3 categories based on the GRWR of the grafts they received. Groups 1, 2, and 3 included patients with GRWR 0.8%, between 0.65% and 0.8%, and <0.65%, respectively. The 56 (6.5%) adult liver transplants were performed in patients weighing 100 kg or more. Except for higher mean body mass index (35.8 versus 25.2 kg/m 2 ; P value < 0.01) and grafts of lower GRWR in obese patients (0.74% versus 1.02%; P value < 0.01), all other parameters were similar between the 2 groups. Despite obesity and smaller grafts, the posttransplant outcomes such as day to normal bilirubin and international normalized ratio; infective, respiratory, and biliary complications; and hospital mortality were similar between the 2 groups. On comparing obese patients in the 3 GRWR categories, except for graft weight (985 versus 769 versus 646 g; P value < 0.01), all the pretransplant parameters were comparable. There was no significant difference in terms of graft function, postoperative morbidity, and hospital mortality between patients with grafts of normal GRWR and those with grafts of low and very low GRWR. Grafts of low GRWR give satisfactory results in obese patients undergoing LDLT and obesity does not adversely impact the outcome of LDLT.