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This retrospective study reviews our experience in surveillance and early detection of cholangiocarcinoma (CC) and in using en bloc total hepatectomy-pancreaticoduodenectomy-orthotopic liver transplantation (OLT-Whipple) to achieve complete eradication of early-stage CC complicating primary sclerosing cholangitis (PSC). Asymptomatic PSC patients underwent surveillance using endoscopic ultrasound and endoscopic retrograde cholangiopancreatography (ERCP) with multilevel brushings for cytological evaluation. Patients diagnosed with CC were treated with combined extra-beam radiotherapy, lesion-focused brachytherapy, and OLT-Whipple. Between 1988 and 2001, 42 of 119 PSC patients were followed according to the surveillance protocol. CC was detected in 8 patients, 6 of whom underwent OLT-Whipple. Of those 6 patients, 4 had stage I CC, and 2 had stage II CC. All 6 OLT-Whipple patients received combined external-beam and brachytherapy radiotherapy. The median time from diagnosis to OLT-Whipple was 144 days. One patient died 55 months post-transplant of an unrelated cause, without tumor recurrence. The other 5 are well without recurrence at 5.7, 7.0, 8.7, 8.8, and 10.1 years. In conclusion, for patients with PSC, ERCP surveillance cytology and intralumenal endoscopic ultrasound examination allow for early detection of CC. Broad and lesion-focused radiotherapy combined with OLT-Whipple to remove the biliary epithelium en bloc offers promising long-term, tumor-free survival. All patients tolerated this extensive surgery well with good quality of life following surgery and recovery. These findings support consideration of the complete excision of an intact biliary tree via OLT-Whipple in patients with early-stage hilar CC complicating PSC. Liver Transpl 14: [279][280][281][282][283][284][285][286] 2008 Hilar cholangiocarcinoma (CC) is a deadly malignant tumor that arises from the bile duct epithelium. 1 CC is often diagnosed at an untreatable advanced stage. National tumor registry data show that approximately two-thirds of patients with CC have, at minimum, regional lymph node or adjacent organ involvement at presentation. Such advanced disease is uniformly fatal. 2 Although surgical strategies afford patients the best chance for short-term survival, with resection, 5-year survival is less than 50%, despite a notably high rate (nearly 90%) of complete excision. [3][4][5][6][7][8][9][10][11] Orthotopic liver transplantation (OLT) for otherwise unresectable CC has also been associated with limited success, with 5-year survival reported to range from 0% to 55% (transplant registry data: 23%). 4,[12][13][14][15][16][17][18][19][20] Because of this poor survival after OLT, CC has become recognized as a contraindication to OLT (except in experimental protocols). However, a recent report describing chemoirradiation followed by OLT for early-stage CC located above the cystic duct demonstrated encouraging 5-year Abbreviations: CC, cholangiocarcinoma; ERCP, endoscopic retrograde cholangiopancreatography; EUS, endoscopic ultrasound ex...

Fructose intolerance may cause unexplained GI symptoms. The higher yield of positive tests in our initial study may be due to referral bias or testing conditions; lower test dose produced a lower yield. Nonetheless, recognition and treatment of fructose intolerance may help many patients.

Micellar cholesterol uptake and secretion were investigated in the human intestinal cell line CaCo-2 following depletion of apical membrane sphingomyelin. The addition of exogenous sphingomyelinase, which hydrolysed 60% of prelabelled sphingomyelin, resulted in a 50% decrease in the uptake of cholesterol from bile salt micelles. The flux of membrane cholesterol into the cell by the hydrolysis of membrane sphingomyelin decreased the rate of cholesterol synthesis by 43% and inhibited hydroxymethylglutaryl-CoA reductase activity by 54%. Moreover, the rate of cholesterol esterification was increased 4-fold. Total cellular cholesterol mass was unchanged by the addition of sphingomyelinase; however, cholesteryl esters increased by 50% and the amount of unesterified cholesterol decreased significantly. The basolateral secretion of cholesterol mass was also decreased following sphingomyelin hydrolysis. Human pancreatic juice was found to contain neutral sphingomyelinase activity which required taurocholate for full expression. The presence of neutral sphingomyelinase activity was also documented in membranes prepared from CaCo-2 cells and in whole homogenates from human duodenal biopsies. The data suggest that the amount of sphingomyelin present in the apical membrane of the intestinal absorptive cell regulates cholesterol uptake from bile salt micelles. Sphingomyelinase activity within intestinal cells and in pancreatic juice could alter the sphingomyelin content of brush-border membranes of small intestinal absorptive cells and thus regulate the amount of cholesterol absorbed by the gut.

BACKGROUNDBilateral vs unilateral biliary stenting is used for palliation in malignant biliary obstruction. No clear data is available to compare the efficacy and safety of bilateral biliary stenting over unilateral stenting.AIMTo assess the efficacy and safety of bilateral vs unilateral biliary drainage in inoperable malignant hilar obstruction.METHODSPubMed, Embase, Scopus, and Cochrane databases, as well as secondary sources (bibliographic review of selected articles and major GI proceedings), were searched through January 2019. The primary outcome was the re-intervention rate. Secondary outcomes were a technical success, early and late complications, and stent malfunction rate. Pooled odds ratio (OR) and 95% confidence interval (CI) were calculated for each outcome.RESULTSA total of 9 studies were included (2 prospective Randomized Controlled Study, 5 retrospective studies, and 2 abstracts), involving 782 patients with malignant hilar obstruction. Bilateral stenting had significantly lower re-intervention rate compared with unilateral drainage (OR = 0.59, 95%CI: 0.40-0.87, P = 0.009). There was no difference in the technical success rate (OR = 0.7, CI: 0.42-1.17, P = 0.17), early complication rate (OR = 1.56, CI: 0.31-7.75, P = 0.59), late complication rate (OR = 0.91, CI: 0.58-1.41, P = 0.56) and stent malfunction (OR = 0.69, CI: 0.42-1.12, P = 0.14) between bilateral and unilateral stenting for malignant hilar biliary strictures.CONCLUSIONBilateral biliary drainage had a lower re-intervention rate as compared to unilateral drainage for high grade inoperable malignant biliary strictures, with no significant difference in technical success, and early or late complication rates.

Despite advancements in endoscopic palliation, operative bypasses are still commonplace in patients with unresectable pancreatic head cancer. In this study, patients treated with operative procedures had a high rate of complications without a notable improvement in outcome. These findings highlight the importance of identifying unresectable disease prior to surgery and support a selective approach to palliative operations.

Thoracoscopic SPL offers short-term relief of pain from chronic pancreatitis, but the relief is not durable in most cases. Similarly, there are short-term improvements in degree of disability, mood, and freedom from narcotic use that are not sustained in the long-term. Nevertheless, two-thirds of patients stated that they would have the surgery again.