Intraductal papillary mucinous neoplasm of the intrahepatic bile duct: a review of literature and a rare case report.

Background: Intraductal papillary neoplasm of the bile duct is a rare variant of bile duct tumors, which is characterized by papillary or villous growth inside the bile duct. Having papillary and mucinous features such as those found in pancreatic intraductal papillary mucinous neoplasm (IPMN) is extremely rare. We report a rare case of intraductal papillary mucinous neoplasm of the intrahepatic bile duct. Case report: A 65-year-old male Caucasian with multiple comorbidities presented to the emergency room with moderate constant pain at the right upper quadrant (RUQ) abdomen for the last several hours. On physical examination, he was found to have normal vital signs, with icteric sclera and pain on deep palpation at the RUQ region. His laboratory results were significant for jaundice, elevated liver function tests and creatinine, hyperglycemia, and leukocytosis. Multiple imaging studies revealed a 5 cm heterogeneous mass in the left hepatic lobe that demonstrated areas of internal enhancement, mild gall bladder wall edema, dilated gall bladder with mild sludge, and 9 mm common bile duct (CBD) dilatation without evidence of choledocholithiasis. He underwent a CT-guided biopsy of this mass, which revealed intrahepatic papillary mucinous neoplasm. This case was discussed at the hepatobiliary multidisciplinary conference, and the patient underwent an uneventful robotic left partial liver resection, cholecystectomy, and lymphadenectomy. Conclusion: IPMN of the biliary tract may represent a carcinogenesis pathway different from that of CBD carcinoma arising from flat dysplasia. Complete surgical resection should be performed whenever possible because of its significant risk of harboring invasive carcinoma.

Distinction between Mitochondrial Antibody-Positive and -Negative Primary Biliary Cholangitis.

Antimitochondrial antibody-positive primary biliary cholangitis (AMA-pos PBC) is an autoimmune disorder in which monoclonal antibodies are produced against epitopes in the mitochondrial membranes of biliary epithelial cells, resulting in progressive nonsuppurative biliary cholangitis. Up to 5% of patients lack these autoantibodies, termed antimitochondrial antibody-negative (AMA-neg) PBC. Although a somewhat new variant of AMA-pos PBC, it is not an overlapping syndrome. Few studies to date have described this phenomenon. An 87-year-old woman was referred to our clinic with elevated serum alkaline phosphatase (714 U/L). She reported fatigue but no other symptoms. A physical examination revealed a benign lesion and bilateral lower extremity swelling secondary to lymphedema. The serological profile was significant for a high antinuclear antibody titer (>1:2,560) with a centromere pattern and negative for antimitochondrial antibody (AMA). The hepatitis panel was negative for viruses A, B, and C. Her serum immunoglobulin G level was 871 mg/dL (normal, <1,600 mg/dL). The rest of the serological tests, including anti-smooth muscle antibodies (ASMA) and anti-liver/kidney microsomal antibodies, were negative. Computed tomography of the abdomen and pelvis without contrast showed normal liver parenchyma and no acute intra-abdominal pathology. Histopathology indicated florid duct lesions. The background parenchyma showed no significant steatosis, and inflammatory changes were limited to the portal areas. Periodic acid-Schiff staining revealed intact hepatic parenchyma and architecture. The patient was diagnosed with AMA-neg PBC and responded well to ursodeoxycholic acid therapy. This case highlights the importance of recognizing AMA-neg PBC as a variant of AMA-pos PBC and differentiating between them. Autoimmune cholangitis is a vague and imprecise condition. All patients with AMA-negative PBC should be tested for other PBC-specific autoantibodies. Although the prognosis and bile duct damage and loss are worse in AMA-neg PBC for unknown reasons, treatment remains the same for both.

Cholestatic liver diseases: An era of emerging therapies.

Recently the field of cholestasis has expanded enormously reflecting an improved understanding of the molecular mechanisms underlying bile secretion and its perturbation in chronic cholestatic disease. Novel anti-cholestatic therapeutic options have been developed for patients not favorably responding to ursodeoxycholic acid (UDCA), the current standard treatment for cholestatic liver disease. Important novel treatment targets now also include nuclear receptors involved in bile acid (BA) homoeostasis like farnesoid X receptor and G protein-coupled receptors e.g., the G-protein-coupled BA receptor "transmembrane G coupled receptor 5". Fibroblast growth factor-19 and enterohepatic BA transporters also deserve attention as additional drug targets as does the potential treatment agent norUDCA. In this review, we discuss recent and future promising therapeutic agents and their potential molecular mechanisms in cholestatic liver disorders.

Portal-endocrine and gastric-exocrine drainage technique of pancreas transplantation provides an easy access for evaluation of pancreatic allograft dysfunction: six-year experience at a single center.

BACKGROUND: The aim of this study is to report our six-year experience with portal-endocrine and gastric-exocrine drainage technique of pancreatic transplantation, which was first developed and implemented at our center in 2007. METHODS: In this study, the outcomes of all patients at our center who had pancreas transplantation with portal-endocrine and gastric-exocrine drainage technique were evaluated. RESULTS: From October 2007 to November 2013, 38 patients had pancreas transplantation with this technique - 31 simultaneous kidney pancreas and seven pancreas alone. Median duration of follow-up was 3.8 years. One-, three-, and five-year patient and graft survival rates were 94%, 87%, 70% and 83%, 65%, 49%, respectively. For pancreas allograft dysfunction evaluation, 51 upper endoscopies were performed in 14 patients; donor duodenal biopsies were successfully obtained in 45 (88%). We detected nine episodes of acute rejection (eight patients) and seven episodes of cytomegalovirus (CMV) duodenitis (six patients). No patient developed any complication due to upper endoscopy. CONCLUSIONS: Portal-endocrine and gastric-exocrine drainage technique of pancreas transplantation provides lifelong easy access to the transplanted duodenum for evaluation of pancreatic allograft dysfunction.

Kinetics and metabolism of fomepizole in healthy humans.

CONTEXT/OBJECTIVE: Fomepizole, a potent inhibitor of alcohol dehydrogenase, has replaced ethanol as antidote for methanol and ethylene glycol intoxications because of a longer duration of action and fewer adverse effects. Prior human studies have indicated that single doses of fomepizole are eliminated by Michaelis-Menten kinetics, but two studies in poisoned patients have suggested that first order elimination occurs after multiple doses. Because of the contrast in fomepizole kinetics among existing studies and the lack of information regarding its metabolism in humans, kinetic and metabolic studies were conducted after single doses and after multiple oral doses in healthy human subjects. MATERIALS/METHODS: In a single-dose, crossover study, healthy humans received fomepizole IV or orally (7 mg/kg). Also to define the metabolism and kinetics of fomepizole when administered over the presumed antidotal period, subjects were divided into three groups, which were given oral loading doses of 10-15 mg/kg, followed by supplemental doses of 3-10 mg/kg/12 h through 96 hours. RESULTS: The single dose study confirmed that fomepizole was eliminated by saturable, nonlinear kinetics, primarily by metabolism, and subsequent renal excretion of the metabolite 4-carboxypyrazole (4-CP). In the multi-dose study, the zero order elimination rate of fomepizole increased with increasing duration of treatment (from mean of 3 µmol/L/h after first dose to 14 µmol/L/h after 72 hours). Consistent with the enhanced elimination of fomepizole, the rate of urinary excretion of 4-CP increased with time. After 96 hours, fomepizole elimination apparently changed to first order kinetics with a t(½) of 1.5-2 hours. DISCUSSION/CONCLUSION: The results suggest that fomepizole induces its own metabolism via cytochrome P-450, leading to enhanced fomepizole elimination and 4-CP excretion. Thus, to maintain relatively constant plasma levels of fomepizole during therapy, increased supplemental doses at about 36-48 hours are needed to overcome the increased elimination of fomepizole. As such, these kinetic evaluations in healthy humans support the current dosing recommendations for fomepizole.