Multi-Center Analysis of Liver Transplantation for Combined Hepatocellular Carcinoma-Cholangiocarcinoma Liver Tumors

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Targeting the PI3K/AKT/mTOR pathway in biliary tract cancers: A review of current evidences and future perspectives

Biliary tract cancers (BTCs) are a group of invasive neoplasms, with increasing incidence and dismal prognosis. In advanced disease, the standard of care is represented by first-line chemotherapy with cisplatin and gemcitabine. In subsequent lines, no clear recommendations are currently available, highlighting the need for novel therapeutic approaches.The PI3K/AKT/mTOR pathway is a core regulator of cell metabolism, growth and survival, and is involved in BTCs carcinogenesis and progression. Mutations, gene copy number alterations and aberrant protein phosphorylation of PI3K, AKT, mTOR and PTEN have been thoroughly described in BTCs and correlate with poor survival outcomes.Several pre-clinical evidences state the efficacy of PI3K/AKT/mTOR pathway inhibitors in BTCs, both in vitro and in vivo. In the clinical setting, initial studies with rapamycin analogs have shown interesting activity with an acceptable toxicity profile. Novel strategies evaluating AKT and PI3K inhibitors have risen serious safety concerns, pointing out the need for improved patient selection and increased target specificity for the clinical development of these agents, both alone and in combination with chemotherapy.This review extensively describes the role of the PI3K/AKT/mTOR pathway in BTCs and examines the rationale of its targeting in these tumors, with particular focus on clinical activity, toxicities and perspectives on further development of PI3K/AKT/mTOR pathway inhibitors.     

Improvement of refractory pruritus after lipoprotein‐apheresis in arthrogryposis‐renal failure‐cholestasis syndrome

Accumulation of bile acids can lead to invalidating pruritus in cholestatic patients. Few reports exist on the influence of lipoprotein‐apheresis (LA) on plasma level of total bile acids (tBA). We report of significant decrease in tBA levels and drastic improvement of pruritus in a 5‐year‐old girl with arthrogryposis‐renal failure‐cholestasis syndrome. We present LA as a suitable rescue treatment option in therapy‐refractory cholestasis‐associated pruritus, at least as bridge until a long‐term solution such as entero‐biliary anastomosis or transplantation is possible.     

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??Abstracts??Objective Different diagnostic methods of biliary atresia ??BA?? and infantile intrahepatic cholestasis disease were investigated in order to find a simple?? fast??practical??economic and non invasive differential diagnostic method. Methods A total of 584 cases of infantile cholestasis were collected from May 2006 to June 2012 for persistent jaundice??pale yellow or white shit who lived in Department of Pediatric Digestion and Infection?? Tongji Hospital?? Tongji Medical College?? Huazhong University of Science & Technology??HUST??. Seven methods including clinical diagnosis??blood biochemical tests?? liver and gallbladder ultrasonography?? dynamic continuous duodenal liquid bile check?? nuclide hepatic imaging?? magnetic resonance imaging and histology were applied for differential diagnosis and the results were analyzed. Results The correctness of clinical diagnosis method was 74.5%?? sensitivity 81.6%??specificity 69.9%?? liver size: 49.0%??89.0%?? and76.9%?? stool color:83.2%??96.1% and96.7%??blood total bilirubin:63.0%??93.1%and91.2% ?? serumγ-GT:79.7%?? 71.1%and78.7% ?? dynamic duodenal liquid color check:93.3%??91.7% and92.7%?? bile acid of duodenal liquid:97.8%??100.0% and 100.0%??B graphy :89.7%??91.7%and94.3%??porta fibre block check:72.1%??29.4%and 68.7%??nuclide hepatic imaging :60.5%??100.0% and 100.0%??MRCP:88.3%??96.5%and94.4%??liver pathology :97.4%??98.2% and 94.9%. Conclusion Differential diagnosis in 1 week can help differentiate biliary atresia from infantile intrahepatic cholestasis. B-ultrasonography and dynamic duodenal fluid test are simple?? fast practical??economic and noninvasive as differential diagnostic methods.     

Transjugular intrahepatic portosystemic shunt versus open splenectomy and esophagogastric devascularization for portal hypertension with recurrent variceal bleeding

BACKGROUND: Transjugular intrahepatic portosystemic shunt (TIPS) and open splenectomy and esophagogastric devascu-larization (OSED) are widely used to treat patients with portal hypertension and recurrent variceal bleeding (PHRVB). This study aimed to compare the effectiveness between TIPS and OSED for the treatment of PHRVB.METHODS: The data were retrospectively retrieved from 479 cirrhotic patients (Child-Pugh A or B class) with PHRVB, who had undergone TIPS (TIPS group) or OSED (OSED group) between January 1, 2010 and October 31, 2014.RESULTS: A total of 196 patients received TIPS, whereas 283 underwent OSED. Within one month after TIPS and OSED, the rebleeding rates were 6.1% and 3.2%, respectively (P=0.122). Significantly lower incidence of pleural effusion, splenic vein thrombosis, and pulmonary infection, as well as higher hepatic encephalopathy rate, shorter postoperative length of hospital stay, and higher hospital costs were ob-served in the TIPS group than those in the OSED group. Dur-ing the follow-up periods (29 months), significantly higher incidences of rebleeding (15.3% vs 4.6%, P=0.001) and hepatic encephalopathy (17.3% vs 3.9%, P=0.001) were observed in the TIPS group than in the OSED group. The incidence of in-stent stenosis was 18.9%. The survival rates were 91.3% in the TIPS group and 95.1% in the OSED group. The long-term liver function did not worsen after either TIPS or OSED.CONCLUSION: For the patients with liver function in the Child-Pugh A or B class, TIPS is not superior over OSED in terms of PHRVB treatment and rebleeding prevention.