Long-term impact of scheduled regular endoscopic interventions for patients with primary sclerosing cholangitis.

BACKGROUND: Primary sclerosing cholangitis (PSC) is associated with biliary obstructions that can require endoscopic retrograde cholangiopancreatography (ERCP). While the beneficial effects of ERCP are well documented, follow-up interventional strategies are less defined, and their long-term impact is debated. METHODS: We evaluated the outcome of a scheduled program of ERCP-guided interventions that have been developed and implemented at our tertiary liver center for more than 20 years. Within our center, follow-up ERCPs were performed at regular intervals to treat previously detected morphological stenosis independent of clinical symptoms. We calculated the transplant-free survival (TFS) of patients who were enrolled in the scheduled ERCP program and compared it to patients who received follow-up ERCPs only on clinical demand. Moreover, we documented the occurrence of hepatic decompensation, recurrent cholangitis episodes, hepatobiliary malignancies, and endoscopy-related adverse events. RESULTS: In our retrospective study, we included 201 patients with PSC who all received an ERCP. In all, 133 patients received scheduled follow-up ERCPs and 68 received follow-up ERCPs only on demand. The rates of TFS since initial diagnosis (median TFS: 17 vs. 27 y; P = 0.020) and initial presentation (median TFS: 16 vs. 11 y; P = 0.002) were higher in patients receiving scheduled versus on-demand ERCP. Subgroup analysis revealed that progression in cholangiographic findings between the first and second ERCP was associated with a poorer outcome compared to patients without progression (17 y vs. undefined; P = 0.021). CONCLUSION: In conclusion, we report the outcome data of a scheduled follow-up ERCP program for patients with PSC in an experienced high-volume endoscopy center. Our data suggest the initiation of multicenter randomized controlled prospective trials to explore the full potential of regular endoscopic follow-up treatment as a strategy to prevent disease progression in patients with PSC.

When malignancy hits twice - synchronous gastric carcinoma and non-Hodgkin-B-cell lymphoma in a patient with common variable immunodeficiency.

Patients with common variable immunodeficiency (CVID) generally bear a higher risk of non Hodgkin B-cell lymphomas and solid tumors, in particular gastric adenocarcinoma.Here we report a case of a 58-year-old male CVID patient who developed both malignancies within a very short period, as documented by two subsequent esophagogastroduodenoscopies performed within 4 months. While the first upper gastrointestinal endoscopy for routine surveillance purposes was uneventful, the second one after developing unexplained weight loss revealed two new neoplastic lesions in the stomach. The histological evaluation revealed a poorly differentiated adenocarcinoma infiltrating the muscularis propria forcing gastrectomy as well as a high-grade B-non-Hodgkin-lymphoma with detection of a MYC- and BCL6-translocation, necessitating chemotherapy with R-CHOP.This case emphasizes the necessity of high awareness for gastric neoplasia in patients with CVID and highlights the need of a standardized yet not established endoscopic surveillance protocol for this vulnerable group.

Liver Regeneration-Related Cytokine Profiles in Donors and Recipients Before and After Living-Donor Liver Transplant.

OBJECTIVES: The liver's capability to completely regenerate after injury is a unique phenomenon in which cytokines are of particular interest. Here, we aimed to assess the release patterns and prognostic relevance of liver regeneration-related cytokines in the setting of living-donor liver transplant. MATERIALS AND METHODS: Eleven cytokines related to liver regeneration (hepatocyte growth factor, interleukin 6, insulin-like growth factor-1, tumor necrosis factor alpha, transforming growth factor beta, granulocyte colony-stimulating factor, stem cell factor, chemokine (C-X-C motif) ligand 12, angiogenin, fibroblast growth factor-2, and vascular endothelial growth factor) were compared in 13 living-donor liver transplant recipients and their corresponding donors before and daily (10 days) after transplant. Patients and donors were stratified by clinical outcomes (early graft loss within 4 weeks after transplant vs beneficial outcome). RESULTS: Most cytokines tested (especially tumor necrosis factor alpha and stem cell factor) were elevated in recipients versus donors. Many cytokines were also increased in recipients with graft loss (especially CXCL12) and in donors of recipients with beneficial outcomes (especially fibroblast growth factor 2). Fibroblast growth factor 2 levels were also correlated positively with serum gamma-glutamyltransferase, and higher preoperative concentrations in donors were associated with recipients having beneficial outcomes, indicating an improved regenerative capacity. In contrast, elevated CXCL12 levels in recipients before and after LDLT predicted graft loss and were linked to ongoing liver damage. CONCLUSIONS: In living-donor liver transplant, there are distinct differences between donors and recipients regarding the release of liver regeneration-related cytokines. Moreover, fibroblast growth factor 2 and CXCL12 may be of diagnostic value in a complementary way to describe or even predict the possible outcomes after transplant. These results may be of clinical interest not only for living-donor liver transplant but also for acute liver failure.

Multiple plastic stents versus covered metal stent for treatment of anastomotic biliary strictures after liver transplantation: a prospective, randomized, multicenter trial.

BACKGROUND AND AIMS: Treatment of anastomotic biliary strictures (ABSs) after orthotopic liver transplantation by endoscopic insertion of multiple plastic stents (MPSs) is well established. The use of covered self-expandable metal stents (cSEMSs) for this indication is less investigated. METHODS: In an open-label, multicenter, randomized trial, patients with confirmed ABSs were randomly assigned 1:1 to receive either an MPS or a cSEMS. The primary endpoint was the number of endoscopic interventions until ABS resolution. Secondary endpoints were frequency of adverse events, treatment success rates, and time to treatment success and recurrence of ABS during follow-up of at least 1 year. RESULTS: Fifty-eight patients were included between 2012 and 2015, and 48 patients completed follow-up. Patients receiving MPS (n = 24) underwent a median of 4 (range, 3-12) endoscopic retrograde cholangiography examinations, whereas those in the cSEMS group (n = 24) underwent a median of 2 (range, 2-12) sessions until ABS resolution (P < .001). A median of 8 (range, 2-32) stents was used until ABS resolution within the MPS group and 1 (range, 1-24) in the cSEMS group (P < .0001). cSEMS migration occurred in 8 (33.3%) patients. Treatment duration did not differ significantly. Initial treatment success rates were high with 23 (95.8%) in the MPS group and 24 (100%) for cSEMSs (P = 1). Five (20.8%) patients in both groups showed stricture recurrence after a median follow-up of 500 days (range, 48-1317 days). CONCLUSIONS: cSEMSs for treatment of ABSs needed less endoscopic interventions to achieve similar efficacy as MPS and might become a new treatment standard. However, the optimal duration of cSEMS therapy and cost-efficacy have to be evaluated. (Clinical trial registration number: NCT01393067.).

Non-alcoholic fatty liver disease progresses to hepatocellular carcinoma in the absence of apparent cirrhosis.

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in developed countries, and accumulating evidence suggests it as the hepatic manifestation of the metabolic syndrome (MS). Although the published prevalence of hepatocellular carcinoma (HCC) is low in NAFLD/NASH patients, most of these data have been derived from areas endemic for viral hepatitis. We recruited 162 adults with HCC between February 2007 and March 2008, investigated the underlying etiologies and determined the prevalence of the MS and related features within each group. Patients with NAFLD/NASH-associated HCC exhibited a higher prevalence of metabolic features (Type 2 diabetes mellitus, hypertension, dyslipidemia, coronary artery disease) compared to non-NAFLD/NASH-HCC. Intriguingly, a significant number (41.7%; p < 0.005) of individuals with NAFLD/NASH-HCC had no evidence of cirrhosis. Patients with alcohol-induced liver disease also displayed many features (14/19, 73.7%) of the MS, although, in contrast to NAFLD/NASH-HCC, alcohol-associated HCC was highly associated with cirrhosis (95.0%; p = 0.064). NAFLD/NASH as the hepatic entity of the MS may itself pose a risk factor for HCC, even in the absence of cirrhosis. The MS may also promote development of HCC among those with alcoholic liver disease. Increased awareness of liver manifestations in the MS may instigate early interventions against developing HCC.

Quantitative liver function tests in donors and recipients of living donor liver transplantation.

The unique ability of the liver to regenerate quickly after resection makes living donor liver transplantation (LDLT) possible. This technique uses the unique ability of the liver to regenerate to full size after partial resection. However, the quality and course of this regeneration process in humans are still widely unexplored. In the present study we investigated the quantitative liver function tests galactose elimination capacity (GEC), indocyanine green half-life (ICG), and lidocaine half-life as markers for the quality of the liver regeneration in the first 3 months after LDLT. In this study, 22 consecutive living liver donors and their corresponding recipients were analyzed at baseline and at 10 and 90 days after LDLT. Six recipients lost their grafts during the study period. We compared donors and recipients at the different time points. After LDLT, GEC decreased (-42.6%) and ICG increased (+50.6%) significantly in donors. ICG and GEC remained significantly altered over 3 months in donors with an improvement between days 10 and 90 (GEC, +59.3%; ICG, -9.1%). ICG and GEC improved significantly in recipients between days 10 and 90 (ICG, -63.7%; GEC, +16.3%). The lidocaine half-life showed no significant changes. The donors had better test results and recovered faster than the recipients. In conclusion, after LDLT the parameters for liver capacity and flow remain altered in donors and recipients despite rapid volume growth.