Neoadjuvant sorafenib combined with gemcitabine plus oxaliplatin in advanced hepatocellular carcinoma

This paper reports the first case of a patient with hepatocellular carcinoma with lymph node metastasis treated by sorafenib combined with gemcitabine plus oxaliplatin,with a partial response and normalization of α fetoprotein,which allowed curative surgery.The potential synergy between these three drugs needs to be confirmed,and is currently being investigated in a randomized phase Ⅱ trial.

Role of frozen section assessment for intraductal papillary and mucinous tumor of the pancreas

Intraductal papillary mucinous neoplasms(IPMN) of the pancreas include a spectrum of dysplasia ranging from minimal mucinous hyperplasia to invasive carcinoma and are extensive tumors that often spread along the ductal tree.Several studies have demonstrated that preoperative imaging is not accurate enough to adapt the extent of pancreatectomy and have suggested routinely using frozen sectioning(FS) to evaluate the completeness of resection and also to check if ductal dilatation is active or passive,in order to avoid an excessive pancreatic resection.Separate main duct and branch duct analysis is needed due to the difference in the natural history of the disease.FS accuracy averages 95%.Eroded epithelium on the main duct,severe ductal inflammation mimicking dysplasia and reactive epithelial changes secondary to obstruction can lead to inappropriate FS results.FS results change the planned extent of resection in up to 30% of cases.The optimal cut-off leading to extend pancreatectomy is not consensual and our standard option is to extend pancreatec-tomy if FS reveals:(1) at least IPMN adenoma on the main duct;or(2) at least borderline IPMN on branch ducts;or(3) invasive carcinoma.However,the decision to extend resection must be taken after a multidisciplinary discussion since it does not exclusively depend on the FS result but also on age,general condition and expected prognosis after resection.The main limitation of using FS is the existence of discontinuous("skip") lesions which account for approximately 10% of IPMN in surgical series and can lead to reoperation in up to 8% of cases.

Disease control with sunitinib in advanced intrahepatic cholangiocarcinoma resistant to gemcitabine-oxaliplatin chemotherapy

Advanced cholangiocarcinoma is associated with poor prognostic survival and has limited therapeutic options available at present. The importance of angiogenesis and expression of pro-angiogenic factors in intrahepatic forms of cholangiocarcinoma suggest that therapies targeting angiogenesis might be useful for the treatment of this disease. Here we report three cases of patients with advanced intrahepatic cholangiocarcinoma progressive after standard chemotherapy and treated with sunitinib 50 mg/d in 6-wk cycles of 4 wk on treatment followed by 2 wk off treatment(Schedule 4/2). In all three patients, sunitinib treatment was associated with a sustained disease control superior to 4 mo, patients achieving either a partial response or stable disease. A reduction in tumor size and density was observed in all cases, suggesting tumor necrosis as a result of sunitinib treatment in these patients. In addition, sunitinib was generally well tolerated and the occurrence of side effects was managed with standard medical interventions, as required. Our results suggest that sunitinib therapy maybe associated with favorable outcomes and tolerability in patients with advanced cholangiocarcinoma. Those observations contributed to launch a prospective phase Ⅱ multicenter trial investigating sunitinib in advanced intrahepatic cholangiocarcinoma(SUN-CK study; NCT01718327).

Metabolic syndrome and non-alcoholic fatty liver disease in liver surgery: The new scourges?

The aim of this topic highlight is to review relevant evidence regarding the influence of the metabolic syndrome(MS) and its associated liver manifestation, non-alcoholic fatty liver disease(NAFLD), on the development of liver cancer as well as their impact on the results of major liver surgery. MS and NAFLD, whose incidences are significantly increasing in Western countries, are leading to a changing profile of the patients undergoing liver surgery. A MEDLINE search was performed for relevant articles using the key words "metabolic syndrome", "liver resection", "liver transplantation", "non alcoholic fatty liver disease", "non-alcoholic steatohepatitis" and "liver cancer". On one hand, the MS favors the development of primary liver malignancies(hepatocellular carcinoma and cholangiocarcinoma)either through NAFLD liver parenchymal alterations(steatosis, steatohepatitis, fibrosis) or in the absence of significant underlying liver parenchyma changes. Also, the existence of NAFLD may have a specific impact on colorectal liver metastases recurrence. On the other hand, the postoperative period following partial liver resection and liver transplantation is at increased risk of both postoperative complications and mortality. These deleterious effects seem to be related to the existence of liver specific complications but also higher cardio-vascular sensitivity in a setting of MS/NAFLD. Finally, the long-term prognosis after curative surgery joins that of patients operated on with other types of underlying liver diseases. An increased rate of patients with MS/NAFLD referred to hepatobiliary units has to be expected. The higher operative risk observed in this subset of patients will require specific improvements in their perioperative management.

Liver transplantation for hepatocellular carcinoma： is zero recurrence theoretically possible？

BACKGROUND： Hepatocellular carcinoma（HCC） recurrence remains a key issue after liver transplantation. This study aimed to determine a subgroup of HCC patients within the Milan criteria who could achieve a theoretical goal of zero recurrence rates after liver transplantation.METHODS： Between 1999 and 2009, 179 patients who received liver transplantation for HCC within the Milan criteria were retrospectively included. Analysis of the factors associated with HCC recurrence was performed to determine the subgroup of patients at the lowest risk of recurrence.RESULTS： Seventy-two percent of the patients received a bridging therapy, including 54 liver resections. Eleven（6.1%） patients recurred within a delay of 19±22 months and ultimately died. Factors associated with recurrence were serum alpha-fetoprotein level 〉400 ng/m L, satellite nodules, poor differentiation, microvascular invasion and cholangiocarcinoma component. Recurrence rates decreased from 6.1% to 3.1% in patients without any of these factors.CONCLUSIONS： Among HCC patients within the Milan criteria, selecting patients with factors based on histology would allow tending towards zero recurrence, and prior histological assessment by liver biopsy or resection may be essential to rule out poorly differentiated tumors, microvascular invasion,and cholangiocarcinoma component.

Hepatic veins as a site of clot formation following liver resection

Pulmonary embolism occurs more frequently after hepatectomy than previously thought but is infrequently associated with peripheral deep vein thrombosis. In this paper, we report 2 cases of postoperative hepatic vein thrombosis after liver resection. Both patients had undergone major hepatectomy of a non-cirrhotic liver largely exposing the middle hepatic vein. Clots were incidentally found in the middle hepatic vein 4 and 17 d after surgery despite routine systemic thrombo-prophylaxis with low molecular weight heparin. Coagulation of the transition plan in a context of mutation of the prothrombin gene and inflammation induced biloma were the likely predisposing conditions. Clots disappeared following curative anticoagulation. We conclude that thrombosis of hepatic veins may occur after liver resection and is a potential source of pulmonary embolism.

Impact of previous cyst-enterostomy on patients' outcome following resection of bile duct cysts

AIM:To analyze the impact of previous cyst-enterostomy of patients underwent congenital bile duct cysts(BDC) resection.METHODS:A multicenter European retrospective study between 1974 and 2011 were conducted by the French Surgical Association.Only Todani subtypes I and IVb were included.Diagnostic imaging studies and operative and pathology reports underwent central revision.Patients with and without a previous history of cystenterostomy(CE) were compared.RESULTS:Among 243 patients with Todani types I and IVb BDC,16 had undergone previous CE(6.5%).Patients with a prior history of CE experienced a greater incidence of preoperative cholangitis(75% vs 22.9%,P < 0.0001),had more complicated presentations(75% vs 40.5%,P = 0.007),and were more likely to have synchronous biliary cancer(31.3% vs 6.2%,P = 0.004) than patients without a prior CE.Overall morbidity(75% vs 33.5%;P < 0.0008),severe complications(43.8% vs 11.9%;P = 0.0026) and reoperation rates(37.5% vs 8.8%;P = 0.0032) were also significantly greater in patients with previous CE,and their Mayo Risk Score,during a median follow-up of 37.5 mo(range:4-372 mo) indicated significantly more patients with fair and poor results(46.1% vs 15.6%;P = 0.0136).CONCLUSION:This is the large series to show that previous CE is associated with poorer short-and longterm results after Todani types I and IVb BDC resection.