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The NCCN Guidelines for Hepatobiliary Cancers provide treatment recommendations for cancers of the liver, gallbladder, and bile ducts. The NCCN Hepatobiliary Cancers Panel meets at least annually to review comments from reviewers within their institutions, examine relevant new data from publications and abstracts, and reevaluate and update their recommendations. These NCCN Guidelines Insights summarize the panel’s discussion and updated recommendations regarding systemic therapy for first-line and subsequent-line treatment of patients with hepatocellular carcinoma.

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Primary fascial closure is often difficult after adult orthotopic liver transplantation (OLT), complicated by donor-to-recipient graft size mismatch, post-reperfusion hepatic edema, coagulopathy, or intestinal edema. Attempts at closing the abdomen under these circumstances can cause increase in intra-abdominal pressures, resulting in significant complications, including graft loss. Temporary closure with silastic mesh has been used as a viable option in children receiving transplants, but there is no experience recorded with its use in adults. A retrospective review was conducted on 200 consecutive liver transplantations performed over 42 months (October 2002 to February 2006. Records were evaluated for patient and donor demographics, perioperative factors including Model for End-Stage Liver Disease and Child-Turcotte-Pugh scores, indications for OLT, ischemic times, blood product administration, and use of temporary silastic mesh closure. Patients requiring silastic mesh were further evaluated for indication, time to primary fascial closure, duration of intubation, length of stay, graft function, and complications (infectious, vascular, biliary, and hernia development). Comparisons were made with a cohort of patients undergoing OLT over the same time period but who were closed primarily, without the use of temporary silastic mesh. Fifty-one liver transplantations (25.5%) of the 200 total transplant cohort used silastic mesh closure. Comparison of the cohorts (primary closure vs. temporary mesh) revealed that no differences existed, except the requirement of all blood products was significantly greater in the silastic mesh group (P Ͻ 0.001). Bowel edema (47.1%) and coagulopathy (37.3%) were the most common indications for mesh closure, with less frequent reasons including donor to recipient size mismatch (11.8%), hemodynamic instability, and a large preexisting fascial defect (2.0% each). The average time from transplant to final fascial closure was 3.4 days (range 2-9 days). In the silastic cohort, 41 transplants where closed primarily, 3 required the addition of synthetic mesh, and 6 had component separation and flap closure. After fascial closure, the mean time to extubation was 1 day. The median length of follow-up was 1.3 years for the silastic closure group. Long-term wound complications in the silastic closure group included 1 instance of colonic fistula, 2 incisional hernias, and 2 wound infections. The 30-day and 1-year patient survival for this group were 93.6 and 82.4%, respectively, and the graft survival for those same periods were 90.2 and 77.7%, respectively. Wound complications, rates of hepatic artery thrombosis or stricture, portal vein thrombosis or stricture, biliary complications, and allograft and patient survival were no different than those in patients undergoing initial primary closure. In adult liver transplantation with a difficult (or potentially difficult) abdomen, temporary closure with silastic mesh was found to allow for uncomplicated fascial closure in a short period of time, wi...

Background Current guidelines recommend laparoscopic cholecystectomy be offered for patients with acute cholecystitis except those deemed as high risk. Few studies have examined the impact of frailty on outcomes for patients undergoing laparoscopic cholecystectomy. Therefore, the aim of this study was to determine the association of frailty with postoperative morbidity and mortality in patients undergoing laparoscopic cholecystectomy for acute cholecystitis. Methods Patients undergoing laparoscopic cholecystectomy for acute cholecystectomy were identified from 2005 to 2010 in the American College of Surgeons National Surgical Quality Improvement Project (NSQIP). The Modified Frailty Index (mFI) was used a surrogate for frailty, and patients were stratified as non-frail (mFI 0), low frailty (mFI 1-2), intermediate frailty (mFI 3-4) and high frailty (mFI ≥ 5). Univariable and multivariable analyses were performed. Receiver operator curves (ROC) and an area under the curve (AUC) were generated to determine accuracy of mFI in predicting postoperative morbidity and mortality. Results Of the 6898 patients undergoing laparoscopic cholecystectomy, 3245 (47%) patients were non-frail. There were 2913 (42%) patients with low-frailty, 649 (9%) patients with intermediate frailty, and 91 (2%) with high frailty. Clavien IV complications were higher for intermediate frail patients (OR 1.81, 95% CI 1.00-3.28, p = 0.050) and high-frail patients (OR 4.59, 95% CI 1.98-10.7, p < 0.001). Additionally, mortality was higher for patients with intermediate frailty (OR 4.69, 95% CI 1.37-16.0, p = 0.014) and high frailty (OR 12.2, 95% CI 2.67-55.5, p = 0.001). The mFI had excellent accuracy for mortality (AUC = 0.83) and Clavien IV complications (AUC = 0.73). Conclusion Frailty is associated with postoperative morbidity and mortality in patients undergoing laparoscopic cholecystectomy for acute cholecystitis.

Contrary to well-recognized bleeding diathesis in chronic liver disease, thrombotic events can occur in these patients due to reduction or loss of synthesis of anticoagulant proteins. Forty-seven consecutive patients with end-stage liver disease (ESLD) were investigated for activity of protein C, protein S, antithrombin, and factor V Leiden mutation. Forty-two (89.4%) patients had low levels of at least 1 while 33 (70.2%) patients were deficient for all anticoagulant proteins studied. Forty-six (97.9%) patients were negative for factor V Leiden mutation. The deficiencies were more marked in hepatitis C virus–positive patients and patients with model for end-stage liver disease (MELD) score >15. Six (12.8%) patients had portal vein thrombosis (PVT), and all had diminished protein S activity. In conclusions, deficiency of anticoagulant proteins occur in early phase of chronic liver disease. The severity of deficiency is proportional to the severity of liver disease. Despite the high prevalence of hypercoagulability, the incidence of PVT is low. Further studies with larger cohort of patients are needed to support these conclusions and to study other associated factors.

Case: A 62-year-old man with cirrhosis, hepatitis C, and hepatocellular carcinoma, underwent a liver transplant. On day 11 after surgery, a chylous leak from a partial wound dehiscence was noted. The leak did not respond to 2 weeks of uninterrupted, fat-free clear liquid diet and 12-hour total parenteral nutrition at night. The same treatment was continued for another 6 weeks with fatty meal challenge every weekend, which he failed. He was then given a fat-free clear liquid diet, 24-hour total parenteral nutrition, and octreotide 100 μg subcutaneously every 8 hours for 14 days. A prompt response was noted. His recovery was excellent at the time of this writing (9 months' follow-up). Discussion: Eleven major cases have been reported with 9 cases being managed conservatively. Four were given a diet plus total parenteral nutrition without octreotide producing a cure in 3 to 36 days. Two cases (including ours) were given the diet and total parenteral nutrition, which failed; octreotide was then added, and these cases were cured in 2 to 4 weeks. Therefore, diet with total parenteral nutrition failed in 33.3% of the cases (2/6). In 3 cases, octreotide was used from the outset. They were all cured in ≤ 2 weeks. One case was operated on for peritonitis; chylous ascites was found and a leak was ligated. One patient with congenital lymphatic disorder underwent peritoneovenous shunting. Octreotide was not used in any of the cases of chylous ascites that were treated surgically. Conclusions:If exploratory surgery is done for any other reason, it is best to identify a chylous leak and ligate it. Otherwise, we recommend octreotide combined with a fat-free, clear liquid diet, and supplementation with medium chain triglycerides and total parenteral nutrition from the outset.

We examined the p53 status of 108 NSCLCs compared to the expression of MLH1 and MSH2 proteins. p53 overexpression was demonstrated by IHC in 64% of patients examined, whereas p53 mutations were detected in 43%. Twenty-two percent of mutations were located outside of the hot-spot (exons 5-8) area. p53 mutations and overexpression were more frequent in SCCL (57% and 73%, respectively) than in lung adenocarcinomas (22% and 50%, respectively). In NSCLC-carrying wild-type p53, increased expression of MSH2 correlated with p53 overexpression (p ‫؍‬ 0.018). In addition, in SCCL, p53 mutations correlated with reduced MSH2 expression (p ‫؍‬ 0.019). These data suggest a relationship between p53 and MSH2. While there is evidence for p53 being a transcriptional activator of MSH2, the hypothesis that MSH2 acts as a DNA-damage signaller triggering p53 overexpression needs to be clarified in future studies. © 2002 Wiley-Liss, Inc. Key words: p53; MSH2; MLH1; non-small cell lung carcinomaThe p53 gene codes for a 53 kDa nuclear phosphoprotein, which holds a key position in the complex network controlling genome stability, the cell cycle and apoptosis. 1 Inactivation of the p53 gene is common in human tumours, 2-5 including NSCLC. 6 -10 A possible role of p53 inactivation as a prognostic marker in lung cancer has been suggested. 8,10 The majority of the p53 mutations described have been detected within exons 5-8, which encode 88% of the DNA-binding domain of the protein. 5 However, there is considerable evidence suggesting that p53 mutations and their biologic effects may have been underestimated since the whole coding region (exons 2-11) of the p53 gene has not been extensively investigated. It has been demonstrated that p53 mutations outside of exons 5-8 account for approximately 20% of the total number of mutations. [11][12][13][14][15] Inactivation of the DNA MMR machinery is associated with the pathogenesis and predisposition of certain malignancies through a mutator phenotype. 16 A possible role of hMLH1 and hMSH2 overexpression in the induction of apoptosis has also been suggested. 17 We have demonstrated that reduced expression of these 2 genes is a frequent event in NSCLC. 18 It has also been demonstrated that LOH at the DNA MMR loci is a frequent genetic event in lung cancer. 19,20 p53 levels increase in response to DNA damage, and this is mainly accomplished through posttranslational modifications. 21 The DNA-PK, ATM and ATR genes are among the known signallers of DNA damage to p53. However, little is known about the relation of MMR genes and p53. The latter can bind in vitro to the promoter region elements of hMSH2 22 and synergise with c-Jun in regulating MHS2 expression. 23 Further support for an MSH2 expression regulatory role of p53 comes from an association between p53 mutations and MSH2 downregulation in human neoplasms. 24,25 We investigated the status of p53 in NSCLC cases from a population in northwest England (Merseyside). In addition, we examined the possible relations of p53 with 2 DNA MMR genes, MLH1 and M...