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Background Biliary intraductal papillary mucinous neoplasm (B-IPMN) has been proposed as a unique clinicopathologic disease with distinct histopathologic features, although wide acceptance remains controversial. A recent consensus conference classified pancreatic IPMN (P-IPMN) into 4 subtypes (ie, gastric, intestinal, pancreatobiliary, oncocytic) based on morphologic appearance and mucin (MUC) staining properties. The aim of this study was to determine whether B-IPMN has similar histopathologic and immunologic subtypes to P-IPMN. Study Design Specific immunostaining for MUC1, MUC2, and deleted for pancreas cancer, locus 4 were performed on specimens from 19 patients with a histopathologic diagnosis of B-IPMN. Immunostaining patterns of B-IPMN were correlated with histopathology. Results Based on histopathology, the following subtypes of B-IPMN were identified: pancreatobiliary n=9 (47%), intestinal n=8 (42%), oncocytic n=2 (11%), and gastric n=0 (0%). Pancreatobiliary and oncocytic subtypes of B-IPMN were positive for MUC1 and negative for MUC2, and intestinal subtypes were positive for MUC2 and negative for MUC1. Thirteen of the 19 B-IPMN were associated with invasive carcinoma; loss of deleted for pancreas cancer, locus 4 was found in 6 of 13 invasive components and in 3 of 19 noninvasive components of B-IPMN. Five-year survival for patients with resected B-IPMN and invasive carcinoma was 38%, which is similar to that for resected P-IPMN with invasive carcinoma. Conclusions Histopathologic subtypes and type-specific MUC expression patterns of B-IPMN resemble those of P-IPMN. MUC1 expression and/or absence of MUC2 expression, which correlate with aggressive features of P-IPMN, were found in B-IPMN and correlate with invasive B-IPMN. Loss of deleted for pancreas cancer, locus 4 parallels the findings observed in P-IPMN. These findings provide additional support that B-IPMN is a unique entity with similarities to main duct P-IPMN.

Background Mirizzi syndrome (MS) is characterized by extrinsic compression of the common hepatic duct by stones impacted in the cystic duct or gallbladder neck. Open cholecystectomy (OC) has been the standard treatment; however, laparoscopy has challenged this approach. Study Design The objective of this study was to review our clinical experience with MS since the introduction of laparoscopic cholecystectomy (LC) and determine the impact of alternative approaches. We conducted a retrospective review of patients with MS from January 1987 to December 2009. Results There were 36 patients with MS among 21,450 cholecystectomies (frequency 0.18%). Seventeen were women. The most common presenting symptoms were abdominal pain (n = 23) and jaundice (n = 19). Preoperative diagnostic studies included ultrasonography (n = 27), CT (n = 24), and endoscopic retrograde cholangiopancreatography (n = 32). Cholecystectomy was performed in 35 patients; LC was initiated in 15 and OC in 21. Conversion rate from LC to OC was 67%. Five patients who had successful LC had type I MS. Of the patients who underwent LC with conversion or OC, 14 had type I and 16 had type II MS. The cystic duct for type I and the bile duct for type II MS were managed diversely according to surgeon's preference. There was no operative mortality. Morbidity was 31% with Clavien class I in 2, IIIa in 4, IIIb in 1, and IV in 3 patients. Mean hospitalization was 9 days (range 2 to 40 days). Mean follow-up was 37 months (range 1 to 187 months). Conclusions Low incidence and nonspecific presentation of MS precludes referral and substantive individual experience. Although LC may be applicable in selected patients with type I MS, OC remains the standard of care.

Background Hepatic resection of metastatic carcinoid cancer can prolong survival and control symptomatic endocrinopathy. Decompensated carcinoid heart disease (CHD) can develop in some patients with metastatic carcinoid cancers, which can preclude operation for resectable hepatic metastases. We hypothesized that outcomes after hepatic resection for patients with the carcinoid syndrome after valve replacement for CHD would be similar to carcinoid patients without CHD. Study Design We compared the survival and symptom control after hepatic resection for patients undergoing valve replacement for CHD to carcinoid patients without CHD matched for age, sex, and extent of hepatectomy. Results Fourteen patients with earlier valve replacement for CHD were compared with 28 carcinoid patients without CHD. All patients had hepatic resection for metastatic carcinoid disease and carcinoid syndrome. Mean age, sex distribution, and extent of hepatectomy (major hepatectomy, 78%) was similar between groups. Mean interval from valve replacement to hepatectomy was 101 days. There was no operative mortality. Major operative morbidity, inclusive of operative blood loss and cardiorespiratory events, occurred in 28.5% and 14.2% for CHD and non-CHD groups, respectively (p = 0.16). Symptom-free survival for CHD and non-CHD groups was 69% and 81% at 1 year (p = 0.22) and 61% and 44% (p = 0.17) at 5 years, respectively. Octreotide-free survival after hepatectomy 69% and 84% (p = 0.15) at 1 year and 62% and 52% (p = 0.29) 5 years, respectively. Overall survival CHD and non-CHD groups 100% at 1 year and 100% and 70% (p = 0.002) 5 years. Conclusions Valve replacement for severe CHD is safe and hepatic resection is associated with similar outcomes as patients without CHD undergoing hepatic resection for carcinoid syndrome. Identifying resectable hepatic metastases from carcinoids in patients with severe CHD should prompt valve replacement and interval hepatic resection.

The basis of hepatocellular injury and progressive fibrosis in a subset of patients with nonalcoholic fatty liver disease (NAFLD) is poorly understood. We sought to identify hepatic proteins that are differentially abundant across the histologic spectrum of NAFLD. Hepatic protein abundance was measured in liver samples from four groups (n = 10 each) of obese (body mass index >30 kg/m2) patients: (1) obese normal group (normal liver histology), (2) simple steatosis (SS), (3) nonalcoholic steatohepatitis (NASH)-mild (steatohepatitis with fibrosis stage 0-1), and (4) NASH-progressive (steatohepatitis with fibrosis stage 2-4). Hepatic peptides were analyzed on an API Qstar XL quadrupole time-of-flight mass spectrometer using Analyst QS software. Linear trends tests were performed and used to screen for differential abundance. Nine known proteins were expressed with differential abundance between study groups. For seven proteins differential abundance is likely to have been on the basis increased hepatic lipid content and/or inflammation. Lumican, a 40-kDa keratin sulfate proteoglycan that regulates collagen fibril assembly and activates transforming growth factor-beta and smooth muscle actin, was expressed similarly in obese normal and SS but was overexpressed in a progressive manner in NASH-mild versus SS (124%, P < 0.001), NASH-progressive versus NASH-mild (156%, P < 0.001) and NASH-progressive versus obese normal (178%, P < 0.001). Fatty acid binding protein-1 (FABP-1), which is protective against the detergent effects of excess free fatty acids, facilitates intracellular free fatty acid transport and is an important ligand for peroxisome proliferator-activated receptor–mediated transcription, was overexpressed in SS when compared to the obese normal group (128%, P < 0.001), but was paradoxically underexpressed in NASH-mild versus SS (73%, P < 0.001), NASH-progressive versus NASH-mild (81%, P < 0.001), and NASH-progressive versus obese normal (59%, P < 0.001). Conclusion: Histologically progressive NAFLD is associated with overexpression of lumican, an important mediator of fibrosis in nonhepatic tissues, whereas FABP-1 is paradoxically underexpressed in NASH, suggesting a new potential mechanism of lipotoxicity in NAFLD. Further studies are needed to determine the biologic basis of lumican and/or FABP-1 dysregulation in NAFLD. (HEPATOLOGY 2009;49:1375–1384.)

Intraductal mucinous papillary neoplasm (IPMN) is being recognized with increasing frequency around the world. The true incidence, however, remains unknown. Our goal was to determine the incidence of IPMN in a population study.We used the records-linkage system of the Rochester Epidemiology Project to ascertain age- and sex-adjusted incidence rates of IPMN in Olmsted County, Minn, from January 1, 1984, to December 31, 2005. We also evaluated the number of prevalent cases as of December 31, 2005.We identified 28 incident cases of IPMN. The age- and sex-adjusted cumulative incidence for IPMN in Olmsted County is 2.04 cases per 100,000 persons (95% confidence interval [CI], 1.28-2.80) from 1984 to 2005. Point prevalence on December 31, 2005, was 25.96 cases per 100,000 persons (95% CI, 14.53-37.38 cases) or 1 per 3852. Restricting to county residents 60 years and older, the point prevalence is 99.10 cases per 100,000 persons (95% CI, 54.40-143.79 cases) or one per 1009 persons. Thirty-two percent of patients were treated surgically. The 5-year survival rate after diagnosis was 59.6%.The incidence of IPMN in Olmsted County is low but increasing. Most patients do not die of complications related to the disease.

performed using techniques of enucleation and renorraphy previously described. Renal function outcomes were stratified based on CKD stages I, II and III. Statistical analysis was performed using pairedsamples T-Test. RESULTS: The distribution of CKD stages is presented in Table 1. Patients with CKD I and II pre-operatively showed no statistically significant increase in creatinine (Cr) or decrease in estimated glomerular filtration (eGFR) was observed post-operatively or at 3 month follow-up (p1⁄40.42 and p1⁄40.36 respectively). For patients with a pre-operative eGFR

Cholangiocarcinoma is a highly-malignant adenocarcinoma originating from cholangiocytes. Current concepts support escape from immune surveillance using aberrant expression of Fas ligand (FasL) and dysregulation of receptor (FasR) signaling as a potential mechanism for tumor progression. Our aims were to determine if altered expression of FasR and FasL or changes in expression of FLICE inhibitor (I-FLICE) allow cholangiocarcinoma cells to escape immune surveillance. Human cholangiocarcinoma cell lines were evaluated for the functional expression of FasR and FasL by (1) quantitating apoptosis after incubation of cells with agonistic antibodies and (2) an in vitro cell death assay involving coculture of cholangiocarcinoma cells with Fas-sensitive thymocytes. I-FLICE antisense treatment was performed by stable transfection with complementary DNA (cDNA) for I-FLICE in the reverse orientation. We found that normal cholangiocytes in vivo express FasL. Human cholangiocarcinoma cell lines express both FasL and FasR and I-FLICE. FasL expressed by cholangiocarcinomas in vitro induced lymphocyte cell death (70% after 24 hours). Despite the expression of FasR, exposure of the cells to agonistic antibodies (500 ng/mL) induced only minimal apoptosis in the Jurkat cells. Antisense treatment of cholangiocarcinomas in vitro with I-FLICE reduced protein expression of I-FLICE by 90% to 95% and increased Fas-mediated apoptosis 2-fold. We concluded that cholangiocarcinomas escape immune surveillance either by disabling FasR signaling through the expression of I-FLICE and/or increased FasL expression to induce apoptosis of invading T cells. Reduction of I-FLICE expression in cholangiocarcinoma cells restored Fas-mediated apoptosis. Therapeutic maneuvers to inhibit expression of I-FLICE may aid in the treatment of cholangiocarcinoma.

Background Adenosquamous carcinoma is a rare malignancy of the exocrine pancreas. Previous literature has reported dismal survival for these patients. We examined our single-institution experience with this tumor to compare survival for sugical resection and palliative therapy. Study design Records were reviewed for patients with adenosquamous pancreatic cancer evaluated during the years 1985 to 2003. Pathology specimens were reviewed. Survival was calculated by Kaplan-Meier method and categorical variables were compared with Chi-square analysis. A p value Results Twenty-three patients were identified with adenosquamous carcinoma of the pancreas. Twelve patients underwent curative resection and 11 patients had either no surgery or a palliative bypass procedure. For the resection group the mean age was 69 years (7 men). In the nonoperative group the mean age was 65 years (6 men). Operative procedures included standard pancreaticoduodenectomy (PD), 4 patients; pyloruspreserving PD, 3 patients; and distal pancreatectomy, 5 patients. Median length of stay was 13.5 days (7–30 d). Morbidity included delayed gastric emptying (4 patients), leak (2 patients), superficial skin infection, abscess, and GI bleed (1 patient each). There was no operative or inhospital mortality in the resection group. For R0 resection median survival was 14.4 months compared to 8 months for R1 and 4.8 months for patients undergoing palliative therapies. Conclusions The retrospective review of our single-institution experience with resection and palliative care for adenosquamous cancer of the pancreas has demonstrated a longer survival for patients that can undergo an R0 resection. Although this is a small series we continue to recommend resection for these patients.