ObjectiveLiver transplantation is an optimal radical therapy for selected patients with hepatocellular carcinoma. The stringent organ allocation system driven by the Milan criteria has been challenged by alternative sets of expanded criteria. Careful analysis is needed to prove that the Milan criteria can be expanded safely and effectively.DesignThis study collectively reviewed 6012 patients of hepatocellular carcinoma from the China Liver Transplant Registry. Expanded criteria were evaluated to characterise an optimised expansion with acceptable outcomes beyond the Milan criteria.ResultsCompared with the Milan criteria, Valencia, University of California, San Francisco, University Clinic of Navarra and Hangzhou criteria provided an expansion of 12.4%, 16.3%, 19.6%, and 51.5%, respectively. The post-transplant survivals of patients fulfilling the expanded criteria were comparable to that of the Milan criteria. The analysis of net reclassification improvement and area under the receiver operating characteristic curves showed an excellent efficiency in recurrence prediction for the expanded criteria compared with the Milan criteria. In patients exceeding Milan but fulfilling the Hangzhou criteria (N=1352), α-fetoprotein (AFP) >100 ng/mL and tumour burden>8 cm were the only two independent prognostic factors (p<0.001). Accordingly, the Hangzhou criteria were stratified as type A (tumour burden ≤8 cm, or tumour burden >8 cm but AFP≤100 ng/mL) and type B (tumour burden >8 cm but AFP between 100 and 400 ng/mL). Type A showed significantly higher 5-year tumour-free survival rates compared with type B (p<0.001).ConclusionsThe Milan criteria can be expanded safely and effectively. The prognostic stratification system based on the Hangzhou criteria serves as a hierarchy of transplant candidates for hepatocellular carcinoma.

CPM may be more prevalent following liver transplantation. Although the diagnosis of CPM after OLT can be made by overall neurologic evaluations including magnetic resonance imaging (MRI) of the head, the mortality is still very high. The occurance of CPM may be associated with such factors as hyponatremia, rapid rise of serum sodium concentration, plasma osmolality increase postoperation, the duration of operation, and high CsA levels.

Abstract.Metformin is an oral anti-hyperglycemic agent of the biguanide family, which is used first-line for type II diabetes with few side-effects. A recent epidemiological study that included 1,828 potential intrahepatic cholangiocarcinoma (ICC) patients showed that metformin use was significantly associated with a 60% reduction in ICC risk in diabetic patients, demonstrating the potential value of metformin in ICC management. In the present study, we firstly showed that metformin exhibited a dose-and time-dependent anti-proliferation effect on ICC cell lines, by mechanisms including apoptosis induction and cell cycle arrest. Metformin targeted the AMPK/mTORC1 pathway in ICC cells. Furthermore, metformin sensitized ICC cells to certain chemotherapeutic agents, such as sorafenib, 5-fluorouracil and As 2 O 3 by targeting the AMPK/mTOR/ HIF-1α/MRP1 pathway and ERK. As it is an inexpensive and widely used antidiabetic drug without severe adverse effects, metformin may be a prospective chemotherapeutic agent or a chemosensitizer in future ICC treatment. IntroductionMetformin, a first-line oral anti-type II diabetes agent used worldwide, displays an antitumorigenesis effect, according to recent epidemic studies (1-3). As compared to insulin or sulfonylureas administration, metformin use may markedly reduce the cancer risk in patients with type II diabetes. Recent studies have confirmed the anti-proliferation effect on various human cancer cell types, such as pancreas (4), prostate (5), breast (6), stomach (7) and liver (8). Metformin inhibits the pro-proliferation effect of insulin receptor-and IGF receptor-dependent signaling by reducing insulin resistance. Furthermore, metformin activates AMP-activated protein kinase (AMPK) and subsequently inhibits activation of mammalian target of rapamycin (mTOR) to prevent proliferation of tumor cells, and activates p53 protein-inducing cell cycle arrest of tumor cells. Several studies have indicated that metformin can potentiate the effect of chemotherapeutic agents or reverse drug resistance in cancer cells (8-10). However, the mechanism of the anti-cancer effects of metformin remains unclear.A recent epidemiological study that included 1,828 potential intrahepatic cholangiocarcinoma (ICC) patients described that metformin use was significantly associated with a 60% reduction in ICC risk in diabetic patients (11). Cholangiocarcinoma (CC)categorized as intrahepatic and extrahepatic cholangiocarcinoma (ECC) is highly lethal. ICC is the second most common type of primary liver cancer and its incidence and mortality rates have been rising in recent decades (12-15). Less than 30% of patients with ICC have the opportunity to have radical operation at diagnostic presentation. Apart from radical operation, some treatment approaches such as systemic chemotherapy, transarterial chemoembolization and radiofrequency ablation may be applied at advanced stages of ICC; however, none of the approaches can significantly improve the prognosis of ICC. Thus, new treatment strategies are needed ...

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Pre-transplant AFP and the dynamic change of AFP after LT were valuable in predicting tumor recurrence after LT for patients with HCC.