Background. Hepatocellular carcinoma (HCC) is the most common primary malignant liver tumor. Currently, liver transplantation may be the optimal treatment for HCC in cirrhotic patients. Patient selection is currently based on tumor size. We developed a program to offer liver transplantation to selected patients with HCC outside of traditional criteria. Methods. Retrospective review for patients transplanted with HCC between April 2008 and June 2017. Patients were grouped by tumor size according to Milan, University of California San Francisco (UCSF), and outside UCSF criteria. Patient demographics, laboratory values, and outcomes were compared. Patients radiographically outside Milan criteria were selected based on tumor control with locoregional therapy (LRT) and 9 months of stability from LRT. α-fetoprotein values were not exclusionary. Results. Two hundred twenty HCC patients were transplanted, 138 inside Milan, 23 inside UCSF, and 59 beyond UCSF criteria. Patient survival was equivalent at 1, 3, or 5 years despite pathologic tumor size. Waiting time to transplantation was not significantly different at an average of 344 days. In patients outside UCSF, tumor recurrence was equivalent to Milan and UCSF criteria recipients who waited >9 months from LRT. Although tumor recurrence was more likely in outside of UCSF patients (3% versus 9% versus 15%; P = 0.02), recurrence-free survival only trended toward significance among the groups (P = 0.053). Conclusions. Selective patients outside of traditional size criteria can be effectively transplanted with equivalent survival to patients with smaller tumors, even when pathologic tumor burden is considered. Tumor stability over time can be used to help select patients for transplantation.

INTRODUCTION: Rhabdomyosarcoma (RMS) is a primary malignancy that arises from the embryonic mesenchyme with the potential to differentiate into skeletal muscle. RMS of the biliary tree is extremely rare. We report a case of an undifferentiated pleomorphic RMS involving the liver and pancreas.PRESENTATION OF CASE: A 62 year old Caucasian woman with rapidly growing abdominal mass and a history of endometrial adenocarcinoma underwent laparotomy due to compression symptoms and concerns of malignancy. Alarge mass arising from the pancreas and extending into the liver was identified and resected with a distal pancreatectomy associated with a left lateral liver segmentectomy. A diagnosis of pleomorphic RMS was made from the pathology specimen. Chemotherapy and radiotherapy were also performed. Unfortunately the patient died 2 years following treatment due to recurrence of the disease.DISCUSSION: P-RMS in the biliary tree is extremely rare (0.5%) and mostly seen in infants and children. Preoperative diagnosis is challenging since the symptoms are unspecific. Preoperative imaging rarely contributes to the final diagnosis. The only possible treatment for adult RMS is surgical resection of the tumor followed by chemotherapy and radiotherapy. Long-term prognosis of P-RMS reported (predominantly of limbs) is poor. To our knowledge, no previous cases of RMS originating from the pancreas have been reported.CONCLUSION: However RMS is an extremely rare tumor in adults, it should be included in the differential diagnosis of patients with atypical pancreatic and liver lesions. (C) 2015 The Authors. Published by Elsevier Ltd. on behalf of Surgical Associates Ltd.

BACKGROUND:Hyper-methylation of CpG dinucleotides in the promoter region of inhibitor of cyclin-dependent kinase 4A (INK4A) has been reported in 60%-80% of hepatocellular carcinoma (HCC). As INK4A promoter hypermethylation event occurs early in HCC progression, the quantification of INK4A promoter methylation in blood sample may represent a useful biomarker for non-invasive diagnosis and prediction of response to therapy.METHODS:We examined INK4A promoter methylation using circulating cell-free DNA (ccfDNA) in a total of 109 serum specimens, including 66 HCC and 43 benign chronic liver diseases. Methylation of the individual seven CpG sites was examined using pyrosequencing.RESULTS:Our results showed that there were significantly higher levels of methylated INK4A in HCC specimens than controls and that the seven CpG sites had different levels of methylation and might exist in different PCR amplicons. The area under receiver operating characteristic (ROC) curve was 0.82, with 65.3% sensitivity and 87.2% specificity at 5% (LOD), 39.0% sensitivity and 96.5% specificity at 7% LOD, and 20.3% sensitivity and 98.8% specificity at 10% LOD, respectively.CONCLUSIONS:Our results support additional studies incorporating INK4A methylation testing of ccfDNA to further validate the diagnostic, predictive, and prognostic characteristics of this biomarker in HCC patients. The knowledge of the existence of epi-alleles should help improve assay design to maximize detection.

Introduction: Nodular Regenerative Hyperplasia (NRH) is a rare noncirrhotic portal hypertensive liver disease characterized by the diffuse transformation of hepatic parenchyma into regenerative nodules without fibrosis. Although the specific etiology has yet to be elucidated, NRH has been associated with various diseases, conditions and medications. Thus, whether NRH occurs from a single unifying pathophysiologic process or multiple different processes is still uncertain. Aims: To characterize biochemical, radiological, and histologic markers of liver disease in patients (pts) with and without NRH in multiple disease cohorts. Methods: Pts with chronic granulomatous disease (CGD), sickle cell disease (SCD), systemic mast cell disease (SMCD), common variable immunodeficiency disease (CVID) and sporadic cases of NRH underwent hepatologic evaluation and liver biopsy for clinical care purposes were evaluated with biomarkers of liver disease, radiologic imaging and histopathologic analysis. Results: 137 pts were evaluated and 56 (41%) were diagnosed with NRH histologically. Of those with NRH, 11 (20%) had CGD, 22 (39%) SCD, 7 (13%) SMCD, 12 (21%) CVID and 4 (7%) sporadic disease. Age at biopsy across all NRH cohorts was significantly older compared to the non-NRH population (mean 40 vs. 33 years, p=0.0128). Patients with NRH had significantly higher alkaline phosphatase (197 vs. 190 U/L, p=0.01), increased liver volumes (2152 vs. 1166 cm3, p=0.01) and increased spleen volumes (after excluding SCD) (1071 vs. 410 cm3, p=0.01), which negatively correlated with platelets ( ρ -0.58, p= 0.002). In the SCD cohort, pts with NRH had increased gamma-glutamyltransferase (128 vs. 67 U/L, p=0.03) and increased lactate dehydrogenase (432 vs. 322 U/L, p=0.01). On histologic evaluation, SCD-NRH pts had increased lobular inflammation (p=0.04). SMCDNRH pts had increased portal and peri-portal inflammation (p=0.005 and p=0.01, respectively), veno-occlusive changes (p=0.04), portal venopathy (p=0.001) and sinusoidal dilation (p=0.03). Conclusions: Despite parallels in clinical disease presentation, histopathologic examination of NRH in separate disease cohorts suggests different mechanistic pathways. Given the potential for multiple etiologies, NRH may be more common than previously thought. Further investigation should focus on the underlying disease process as it may provide a window into biology.

Purpose: A 68-year-old Caucasian man was seen in the hospital for abnormal LFTs. He carried a diagnosis of HHV-8 related plasmablastic T-cell lymphoma. He had undergone treatment with cyclosporine, doxorubicin, vincristine, and prednisone, with initial remission of disease; however, he developed recurrence and was subsequently treated with rituximab 8 months prior to presentation. Before the initiation of chemotherapy, the patient underwent testing for hepatitis B (HBV), which demonstrated he was HBV surface antigen (HBsAg) negative, anti-HBV surface antibody (anti-HBS) positive, and IgM anti-HBV core antibody (anti-HBc IgM) negative. A total anti-HBV core antibody (anti-HBc total) was not checked prior to starting therapy. On the current admission, total bilirubin was 7.9 mg/dL with conjugated fraction of 4.7 mg/dL. AST was elevated to 830 U/L, ALT to 1591 U/L, and alkaline phosphatase to 189 U/L. Serum ANA was positive at a titer of <1:80 and anti-smooth muscle antibody was negative. Ceruloplasmin was noted at 44 mg/dL. Serologies demonstrated HBsAg to be positive, anti-HBs negative, anti-HBc total positive, anti-HBc IgM positive, HBeAg positive, and anti-HBe negative. HBV PCR found 5.81 Log IU viral particles. Furthermore, his hepatitis A virus (HAV) total antibody was positive, and the antiHAV IgM antibody was reactive. His anti-hepatitis E virus (HEV) IgM antibody was also detected, and anti-HEV IgG was negative. Hepatitis D antibody was negative. Liver biopsy showed irregular hepatic plates with hepatocyte dropout, peri-portal infl ammation, multiple apoptotic bodies, and ballooning degeneration. Stage one to two fi brosis was found. Tenofovir 300 mg daily was started for reactivated HBV, and his AST, ALT, and bilirubin declined to normal 16 weeks later. Acute hepatitis resulting from co-infection with multiple hepatotropic viruses may occur. In some instances, the mechanism by which they are contracted and risk factors for their exposure are shared. In the developing world, several case reports and series have described instances where patients presented with serologic evidence for acute infection from both HAV and HEV. Th ese studies have generally been performed in the setting of sporadic cases with clinical syndromes of acute hepatitis. However, the use of serologic testing to establish diagnoses of acute HAV or HEV in these settings is problematic. Serologic tests were designed for cases in which the pretest probability and clinical suspicion for exposure to acute HEV or HAV were high (i.e., epidemic outbreaks or travel to endemic areas). Whether the presence of anti-HAV and HEV in the setting of such sporadic cases are indicative of true co-infection or represent false positive results remains debatable.

Introduction: Esophageal sarcomatoid carcinoma is a rare cause of esophageal malignancies constituting less than 2% of all cases. Presentation is usually secondary to dysphagia, and diagnosis is made by endoscopy and biopsy showing both carcinomatous and sarcomatous components. Endoscopic resection is thought to be safe and effective management option. Case Presentation: We present a 51-year-old male who was complaining of dysphagia for both solids and liquids for the last for 6 weeks with a 20-pound weight loss. An EGD showed a large pedunculated polyp. Ultrasound was then performed and showed a polyp attached to the esophageal wall without infiltration and no large vessels seen on Doppler, and no enlarged mediastinal or paraesophageal lymph nodes. A repeat procedure for excisional biopsy was attempted under maximum anesthesia care. Cardiothorasic surgery team was consulted and was ready to intervene in case complications to endoscopic resection were faced. Biopsy was taken successfully but mass resection using a snare was unsuccessful given its large size. Pathology results showed sarcomatoid carcinoma after which oncology team was consulted and recommended esophagectomy. A month later the patient underwent a transhiatal esophagectomy with gastroplasty and pull-through without any intraoperative complications, though later the course was complicated by controlled anastomosis leak. Discussion: Previously the endoscopic resection was shown to be a safe procedure for esophageal polypoid lesions after assessing the base with endoscopic ultrasound for vascular structures. In this case, that approach was a challenge due to the large size of the tumor. Treatment for esophageal sarcomatoid carcinoma is achieved by endoscopic resection combined with adjunct radiation and chemotherapy.

Incidence of nonalcoholic fatty liver disease is increasing with an estimated prevalence of 20-30% in developed nations. This is leading to increased incidence of chronic liver disease, cirrhosis, and hepatocellular cancer. It is critical to understand the etiology and pathogenesis of any disease to create therapeutic targets and develop new treatments. In this paper we discuss the etiology and pathogenesis of nonalcoholic steatohepatitis with special focus on obesity, role of insulin resistance, and molecular mechanisms of hepatotoxicity.

BACKGROUND AND AIMS:Despite effective vaccine available, hepatitis A remains a significant cause of morbidity and mortality worldwide including acute liver failure, transplantation and death. Vaccination rates for hepatitis A in the general population are low. Rates of hepatitis A vaccination in healthcare personnel (HCP) are unknown. We studied vaccination rate to hepatitis A in a cohort of HCP at a large US academic center.MATERIAL AND METHODS:An anonymous survey was circulated between 499 HCP at-risk of hepatitis A exposure at our Institution. Results were corrected for non-response rate and compared with the general US population using the 2007 CDC-National Immunization Survey. Rate of hepatitis A vaccination was compared with Institutional rate of vaccination for the Influenza 2009-2010 season.RESULTS:Rate of vaccination for hepatitis A in HCP was 28.8% (response rate 41.4%; 207/499), with 58.9% having completed the full series and 24.7% being tested for post-vaccination immunity. Acceptance rate among non-vaccinated subjects was 70.7%. HCP hepatitis A vaccination rate was statistically greater than the national general population (28.8 vs. 12.1%, p ≤ 0.031). A statistically significant greater vaccination rate was found among US born responders vs. foreign-born HCP (34.3 vs. 19.3%, p = 0.0324). Vaccination for hepatitis A was statistically inferior to that of Influenza (28.8 vs. 90%; P = 0.01).CONCLUSIONS:HCP have statistically higher vaccination rate for hepatitis A than the general population, but overall protection remains suboptimal with vaccination rate below those for mandatory vaccines. Further studies to determine whether hepatitis A vaccine is cost-effective in HCP are recommended.

Acute alcoholic hepatitis (AH) is a distinct clinical entity amongst patients with chronic alcohol abuse. Patients with severe AH are at risk of dying in about 20%-25% cases despite specific treatment with corticosteroids and/or pentoxifylline. Clearly, a need for an additional more effective treatment option is unmet currently. Liver transplantation (LT), a definitive treatment option for alcoholic cirrhosis requires 6 mo abstinence. However, this rule cannot be applied to patients with AH as these patients are actively drinking prior to their presentation. Shortage of donors, ethical issues, and fear of recidivism after transplantation with less than 6 mo pre-transplant abstinence are some of the reasons behind this rule of 6 mo of abstinence and hesitancy of transplanting patients with AH. These issues are debated at length in this manuscript. Further, retrospective studies have shown that patients undergoing transplantation for alcoholic cirrhosis and having histological changes of AH have been shown to fare as well when compared to patients without these histological changes. Recently, French workers have reported a case matched prospective study showing encouraging data on the usefulness of LT for patients who are non-responders to corticosteroid and/or pentoxifylline therapy. Future studies are needed to identify patients with severe AH who are going to benefit most with LT. In the light of emerging data on the efficacy of LT in improving survival of patients with severe acute AH who do not respond to corticosteroids, the time is ripe to re-evaluate our policy of LT in patients with AH.

Myotonic dystrophy is a multisystemic disorder characterized by repeat expansion mutations of the dystrophia myotonica protein kinase (DMPK) gene resulting in a defective muscular insulin receptor and insulin resistance. We describe a patient with myotonic dystrophy who developed biopsy-proven non-alcoholic steatohepatitis. We suggest that patients with myotonic dystrophy are at risk of developing steatohepatitis. The relationship between defective insulin receptor and development of steatohepatitis should be further investigated.

BACKGROUNDFor the past two decades multiple series have documented that liver resection has become safer. The purpose of this study was to determine the current status of hepatic resection in the USA by analysing the multi-institutional experience within the National Surgical Quality Improvement Program (NSQIP) dataset.METHODSOf the 363,897 cases in the 2005-2007 NSQIP Participant Use File, 2313 elective open hepatectomy cases were identified (1344 partial, 230 left, 510 right and 229 extended hepatectomies). A total of 57 perioperative risk factors and 28 postoperative complications were compared. To determine the applicability of NSQIP general risk models to hepatic surgery, the prognostic value of standard multivariate analysis was compared with the NSQIP general surgery aggregate risk indices (expected probability of morbidity [morbprob], expected probability of mortality [mortprob]).RESULTSThe median age of patients listed in the database was 60 years; sex distributions were equivalent; 78% were White; 65% of patients had an ASA score of 3 or 4, and the most prevalent co-morbidity was hypertension (46%). A total of 41% of patients had disseminated cancer, 19% of whom had received chemotherapy within 30 days of surgery. The overall 30-day mortality rate was 2.5% (57/2313) and the 30-day major morbidity rate was 19.6% (453/2313). Multivariate analysis identified nine risk factors associated with major morbidity and two risk factors associated with mortality. In contrast, the morbprob and mortprob statistics did not predict outcomes accurately. For those patients who developed major morbidity, the median length of stay was longer (10 vs. 6 days; P = 0.001) and the mortality rate was higher (11.3% vs. 0.3%; P = 0.001).CONCLUSIONSAnalysis of the NSQIP experience with hepatectomy indicates that the current mortality and major morbidity rate benchmarks are 2.5% and 19.6%, respectively. Poor outcomes were associated with nutritional status, liver function and the extent of hepatectomy. The NSQIP general surgery morbprob and mortprob values were relatively poor predictors of post-hepatectomy observed morbidity, indicating the need for specialty-specific NSQIP modelling.