ABSTRACT
AIMS: To evaluate outcomes of ERCP as first-line management in patients with malignant biliary obstruction (MBO) of all causes and stages, reflecting a real-life setting. METHODS: Retrospective observational study of patients with ERCP as the first-line management of MBO at Oslo University Hospital between 2015 and 2021. Primary outcome measure was a ≥ 50% decrease from the pre-procedural bilirubin within 30 days after ERCP. Secondary outcome measures were technical success of ERCP, complications and overall mortality. RESULTS: A total of 596 patients were included, median age 70 years. ASA score was ≥ III in 67% of patients. The most common cancers causing MBO were pancreatic cancer (52%), metastatic lesions (20%) and cholangiocarcinoma (16%). The primary outcome measure was achieved in 62% of patients. With endoscopic access, overall technical success was 80% with 85% for the distal extrahepatic group, 71% for the perihilar, 40% for the intrahepatic and 53% for multiple level MBOs. Reinterventions were performed in 27% of the patients. Complications occurred in 15% of the patients, including post-ERCP pancreatitis in 9%. Most complications were of minor/moderate severity (81%). Overall mortality was 33% within the first 90 days. Patients deceased by the end of the study period (83%) had median survival of 146 days (range 1-2,582 days). CONCLUSIONS: ERCP has a high rate of clinical effect and technical success in the management of both distal extrahepatic and perihilar MBO. Our data indicate that ERCP is a valid option in the first-line management of MBO.
Subject(s)
Bile Duct Neoplasms , Cholestasis , Pancreatic Neoplasms , Humans , Aged , Cholangiopancreatography, Endoscopic Retrograde/adverse effects , Cholangiopancreatography, Endoscopic Retrograde/methods , Cholestasis/complications , Pancreatic Neoplasms/complications , Bile Duct Neoplasms/complications , Bile Ducts, Intrahepatic , Retrospective StudiesABSTRACT
Primary sclerosing cholangitis (PSC) is strongly associated with several human leukocyte antigen (HLA) haplotypes. Due to extensive linkage disequilibrium and multiple polymorphic candidate genes in the HLA complex, identifying the alleles responsible for these associations has proven difficult. We aimed to evaluate whether studying populations of admixed or non-European descent could help in defining the causative HLA alleles. When assessing haplotypes carrying HLA-DRB1*13:01 (hypothesized to specifically increase the susceptibility to chronic cholangitis), we observed that every haplotype in the Scandinavian PSC population carried HLA-DQB1*06:03. In contrast, only 65% of HLA-DRB1*13:01 haplotypes in an admixed/non-European PSC population carried this allele, suggesting that further assessments of the PSC-associated haplotype HLA-DRB1*13:01-DQA1*01:03-DQB1*06:03 in admixed or multi-ethnic populations could aid in identifying the causative allele.
Subject(s)
Cholangitis, Sclerosing/genetics , Genetic Predisposition to Disease , HLA-DQ beta-Chains/genetics , HLA-DRB1 Chains/genetics , Haplotypes , Alleles , Cholangitis, Sclerosing/ethnology , Cholangitis, Sclerosing/immunology , Ethnicity , Gene Expression , Gene Frequency , HLA-DQ beta-Chains/classification , HLA-DQ beta-Chains/immunology , HLA-DRB1 Chains/classification , HLA-DRB1 Chains/immunology , Humans , Linkage Disequilibrium , Scandinavian and Nordic Countries , White PeopleABSTRACT
BACKGROUND: A recent genome-wide association study identified the FUT2 secretor status and genotype defined by the single-nucleotide polymorphism rs601338 as potential genetic risk factor in primary sclerosing cholangitis (PSC), which significantly influences biliary bacterial composition. AIM: To determine the impact of the rs601338-FUT2 genotype on frequency of biliary infections, development of dominant stenosis and liver-transplantation-free survival in patients with PSC. METHODS: Cohort study of 215 patients with PSC treated at our tertiary care centre with respect to their rs601338-FUT2 genotype. Results of endoscopic retrograde cholangiography and bile culture were analysed; 639 biliary samples were obtained, cultured and subjected to microbial analysis. Clinical and laboratory data were analysed using chart reviews. RESULTS: For the rs601338-FUT2 genotype, 69 patients (32.1%) were found to be wildtype (GG), 97 (45.1%) patients were heterozygous (AG) and 49 patients (22.8%) were homozygous-mutated (AA). In addition to alterations in the bacterial pattern, especially in heterozygous carriers, patients with mutated alleles had a marked increase in the frequency of biliary Candida infections (P = 0.025). Further, patients with mutated alleles showed an increased frequency of episodes of cholangitis (P = 0.0025), development of dominant stenosis (P < 0.002) and a reduced actuarial transplantation-free survival (P = 0.044). Levels of biliary Ca19-9 were significantly elevated in the homozygous-mutated patients. CONCLUSIONS: The rs601338-FUT2 genotype is strongly associated with episodes of cholangitis, fungobilia and the incidence of dominant stenosis, which are three clinical hallmarks of PSC; FUT2 is thus an important genetic risk factor for host-microbial diversity and disease progression in PSC.
