Rendezvous procedure for the treatment of bile leaks and injury following segmental hepatectomy

BackgroundEndoscopic retrograde cholangiopancreatography is a minimally invasive procedure used for the evaluation and management of biliary injuries. At times, ERCP fails and percutaneous modalities may be required. Rendezvous procedures are combined endoscopic and percutaneous techniques that have been used to restore anatomic continuity and biliary drainage in cases where retrograde and/or transhepatic access alone has failed either due to anatomic variation or traumatic injury with biloma formation.AimsTo assess if the Rendezvous technique plays a role in establishing biliary continuity in patients with a bile leak after segmental hepatectomy.MethodsWe herby present a series of 3 patients who had complex bile leaks after segmental liver resection and underwent a combined percutaneous and endoscopic Rendezvous procedure to establish biliary continuity.ResultsThis technique was successful in restoring biliary continuity and avoiding hepaticojejunostomy in 2 of the 3 patients.ConclusionThe Rendezvous technique may play a role in establishing biliary continuity in patients with biliary leak secondary to hepatic surgery.     

Controversies Concerning Pathophysiology and Management of Acalculous Biliary-Type Abdominal Pain

Acalculous biliary-type abdominal pain is a commonly encountered clinical problem whose pathophysiology is unclear and evaluation and management are controversial. Cholecystokinin cholescintigraphy to measure the gallbladder ejection fraction (GEF) has been advocated as a criterion for cholecystectomy. However, there is no consensus regarding the dose and rate of infusion of cholecystokinin, both of which can alter the GEF, and the definition of an abnormal ejection fraction varies among studies. Many but not all studies have concluded that a low GEF predicts good outcomes after cholecystectomy, but most studies suffer from poor methodology and there is only one prospective randomized controlled trial. Also, some patients with a normal GEF have responded to cholecystectomy. Another controversial area has been the role of sphincter of Oddi dysfunction (SOD) in patients with biliary-type pain and gallbladder in situ. Some reports suggest an overlap between SOD and low GEF, although a causal relationship has not been established. Yet another subject of interest is the role of visceral hyperalgesia in patients with acalculous biliary-type pain. We have reviewed the relevant literature relating to these issues and have highlighted the controversial aspects. In the absence of high-quality studies, an evidence-based treatment algorithm is difficult to design but will be proposed. More prospective controlled trials are warranted to better define the appropriate evaluation and management of patients with this syndrome.     

Use of microsatellite marker loss of heterozygosity in accurate diagnosis of pancreaticobiliary malignancy from brush cytology samples

BACKGROUND: Brush cytology of biliary strictures to diagnose pancreaticobiliary malignancy suffers from poor sensitivity. AIM: To improve the diagnostic yield of pancreaticobiliary brush cytology through analysis of tumour suppressor gene linked microsatellite marker loss of heterozygosity (LOH) and k-ras codon 12 mutation detection. METHODS: Twenty six patients with biliary strictures underwent endoscopic retrograde cholangiography with brush cytology. A panel of 12 polymorphic microsatellite markers linked to six tumour suppressor genes was developed. Genomic DNA from cell clusters acquired from brush cytology specimens and microdissected surgical malignant and normal tissue underwent polymerase chain amplification reaction (PCR). PCR products were compared for LOH and k-ras codon 12 mutations. RESULTS: Seventeen patients were confirmed to have pancreaticobiliary adenocarcinoma. Nine patients had benign strictures (eight proven surgically, one by follow up). Cytomorphological interpretation was positive for malignancy (n = 8), indeterminate (n = 10), and negative for malignancy (n = 8). Selected malignant appearing cytological cell clusters and microdissected histological samples from cancer showed abundant LOH characteristic of malignancy while brushings from nine cases without cancer carried no LOH (p<0.001). LOH and k-ras mutations profile of the cytological specimens was almost always concordant with the tissue samples. Presence of k-ras mutation predicted malignancy of pancreatic origin (p<0.001). CONCLUSION: LOH and k-ras codon 12 mutation analysis of PCR amplified DNA from biliary brush cytology discriminates reactive from malignant cells, with 100% sensitivity, specificity, and accuracy. Minor variations in LOH in brushings and in different sites within the same tumour likely reflect intratumoral mutational heterogeneity during clonal expansion of pre- and neoplastic lineages.     

Soluble kit receptor in human serum

c-kit encodes the transmembrane receptor tyrosine kinase (Kit) for the recently described ligand stem cell factor (SCF). We have developed an enzyme-linked immunosorbent assay for measuring soluble human Kit and we have used the assay to show high levels of soluble Kit in human serum. The distribution of soluble Kit levels was investigated among 112 normal human serum donors. The mean serum level (+/- SD) was found to be 324 +/- 105 ng/mL with the values falling between 163 ng/mL and 788 ng/mL. No correlation between soluble Kit levels and the sexes or ages of the donors was found. Partial purification using immunoaffinity chromatography allowed us to characterize the soluble Kit from pooled human serum. Antibodies generated to a 497-amino acid recombinant human soluble Kit corresponding to the N-terminal extracellular domain of the receptor recognized the serum-derived soluble Kit by immunoblotting. We found that the serum-derived soluble Kit is glycosylated, with mostly N- linked but also O-linked carbohydrate, and with terminal sialic acid residues. When compared with the recombinant human soluble Kit, the serum-derived material was similar both in size and glycosylation pattern. CNBr cleavage of the isolated serum-derived material followed by amino terminal sequencing confirmed the presence of five peptides expected for the extracellular portion of the Kit molecule. The immunoaffinity purified serum-derived soluble Kit inhibited binding of [125I]SCF to membrane-bound receptor in an in vitro assay. These results indicate that soluble Kit could modulate the activity and functions of SCF in vivo.     

Hepatobiliary disease in inflammatory bowel disease

Many hepatobiliary diseases are seen in IBD. PSC is the most common, occurring in 7.5% of patients with UC. The cause of PSC is not well understood, but PSC seems to be associated with genetic susceptibility, sharing some immunologic abnormalities with UC. A characteristic cholangiogram in a patient with abnormal liver function tests usually establishes the diagnosis. Liver biopsy is not essential but can help make the diagnosis of small duct PSC in patients with a normal cholangiogram. There are no medications that treat PSC effectively. Endoscopic dilation of dominant strictures reduces the frequency of cholangitis and may improve survival. OLT remains the only proven treatment of advanced PSC. Cholangiocarcinoma is a feared complication of PSC that is difficult to diagnose. Cholelithiasis, PBC, portal vein thrombosis, and hepatic abscess are hepatobiliary disorders that occur less frequently in IBD patients.     

Limited contribution of the SPINK1 N34S mutation to the risk and severity of alcoholic chronic pancreatitis: a report from the United States

Mutations in the SPINK1 gene (e.g. N34S) have been reported in patients with idiopathic, familial, tropical, and alcoholic pancreatitis. The prevalence of SPINK1 N34S differs between different patient populations, and its contribution to the risk and the severity of alcoholic chronic pancreatitis has not been defined in the United States. Mutational analysis of the exon 3 was performed in 32 patients with alcoholic chronic pancreatitis, 39 patients with nonalcoholic chronic pancreatitis or recurrent acute pancreatitis, and 190 previously studied healthy controls. The course of alcoholic chronic pancreatitis with and without N34S was compared in age of onset- and sex-matched patients. All SPINK1 gene sequence variations were heterozygous. SPINK1 N34S was present in 3/190 (1.6%) and P55S was found in 2/190 (1.1%) of controls. In alcoholics, the N34S mutation was identified in 2/32 patients (6.3%, P < 0.05). In nonalcoholics, N34S and P55S were identified in 6/39 patients (15.4%, P < 0.005, N34S N = 4, P55S N = 1, N34S/P55S N = 1). The clinical course of alcoholic chronic pancreatitis was similar between patients with and without the N34S mutation. The N34S mutation is uncommon in patients with alcoholic chronic pancreatitis in the United States; its prevalence is similar to other countries and appears not to alter the onset or the severity of alcoholic chronic pancreatitis.     

DNA Mutational Differences in Cytological Specimens from Pancreatic Cancer and Cholangiocarcinoma

Background/Aims: Preoperative distinction between pancreatic cancer (PC) and extrahepatic cholangiocarcinoma (CC) is desirable due to diverging management options, and to optimize enrollment into neoadjuvant trials. Methods: A single-center retrospective study of patients with PC or CC was undertaken. Four blinded pathologists reviewed all cases and reached a consensus diagnosis (PC or CC). Microdissection-based multiple microsatellite loss analysis and direct sequencing of K-ras oncogene was performed and compared for PC and CC. Results: Of 33 cases studied (17 males; 16 PC, 17 CC; 10 with primary sclerosing cholangitis), a K-ras mutation was present in 14/16 (87.5%) PC and 1/17 (5.9%) CC cases (p<0.001), sensitivity and specificity were 87.5 and 94%, respectively. The mean fractional mutational rate was higher in PC (0.51; 95% CI 0.45–0.58) compared to CC (0.34; 95% CI 0.28–0.39, p<0.001). Conclusions: The presence of a K-ras mutation in cytology specimens distinguishes PC from CC in this study.