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.

PuraStat in gastrointestinal bleeding: results of a prospective multicentre observational pilot study.

BACKGROUND: A recently developed haemostatic peptide gel for endoscopic application has been introduced to improve the management of gastrointestinal bleeding. The aim of this pilot study was to evaluate the feasibility, safety, efficacy and indication profiles of PuraStat in a clinical setting. METHODS: In this prospective observational multicentre pilot study, patients with acute non-variceal gastrointestinal bleeding (upper and lower) were included. Primary and secondary application of PuraStat was evaluated. Haemoglobin, prothrombin time, platelets and transfusion behaviour were documented before and after haemostasis. The efficacy of PuraStat was assessed during the procedure, at 3 days and 1 week after application. RESULTS: 111 patients with acute gastrointestinal bleeding were recruited into the study. 70 percent (78/111) of the patients had upper gastrointestinal bleeding and 30% (33/111) had lower gastrointestinal bleeding. After primary application of PuraStat, initial haemostatic success was achieved in 94% of patients (74/79, 95% CI 88-99%), and in 75% of the patients when used as a secondary haemostatic product, following failure of established techniques (24/32, 95% CI 59-91%). The therapeutic success rates (absence of rebleeding) after 3 and 7 days were 91% and 87% after primary use, and 87% and 81% in all study patients. Overall rebleeding rate at 30 day follow-up was 16% (18/111). In the 5 patients who finally required surgery (4.5%), PuraStat allowed temporary haemostasis and stabilisation. CONCLUSIONS: PuraStat expanded the therapeutic toolbox available for an effective treatment of gastrointestinal bleeding sources. It could be safely applied and administered without complications as a primary or secondary therapy. PuraStat may additionally serve as a bridge to surgery in order to achieve temporary haemostasis in case of refractory severe bleeding, possibly playing a role in preventing immediate emergency surgery.

Circulating Bile Acids in Liver Failure Activate TGR5 and Induce Monocyte Dysfunction.

BACKGROUND & AIMS: Retention of bile acids in the blood is a hallmark of liver failure. Recent studies have shown that increased serum bile acid levels correlate with bacterial infection and increased mortality. However, the mechanisms by which circulating bile acids influence patient outcomes still are elusive. METHODS: Serum bile acid profiles in 33 critically ill patients with liver failure and their effects on Takeda G-protein-coupled receptor 5 (TGR5), an immunomodulatory receptor that is highly expressed in monocytes, were analyzed using tandem mass spectrometry, novel highly sensitive TGR5 bioluminescence resonance energy transfer using nanoluciferase (NanoBRET, Promega Corp, Madison, WI) technology, and in vitro assays with human monocytes. RESULTS: Twenty-two patients (67%) had serum bile acids that led to distinct TGR5 activation. These TGR5-activating serum bile acids severely compromised monocyte function. The release of proinflammatory cytokines (eg, tumor necrosis factor α or interleukin 6) in response to bacterial challenge was reduced significantly if monocytes were incubated with TGR5-activating serum bile acids from patients with liver failure. By contrast, serum bile acids from healthy volunteers did not influence cytokine release. Monocytes that did not express TGR5 were protected from the bile acid effects. TGR5-activating serum bile acids were a risk factor for a fatal outcome in patients with liver failure, independent of disease severity. CONCLUSIONS: Depending on their composition and quantity, serum bile acids in liver failure activate TGR5. TGR5 activation leads to monocyte dysfunction and correlates with mortality, independent of disease activity. This indicates an active role of TGR5 in liver failure. Therefore, TGR5 and bile acid metabolism might be promising targets for the treatment of immune dysfunction in liver failure.

Low Incidence of Esophageal Lesions After Pulmonary Vein Isolation Using Contact-Force Sensing Catheter Without Esophageal Temperature Probe.

Pulmonary vein isolation (PVI) is a cornerstone therapy for atrial fibrillation (AF). Although severe complications are rather rare, the development of an atrio-esophageal fistula (AEF) is a fatal complication with a very high mortality even after surgical treatment. The use of esophageal temperature probes (ETP) during PVI may protect the esophagus but it is still under debate since the ETP may also lead to esophageal lesions. The aim of this study was to evaluate the clinical safety of PVI using contact-force (CF) sensing catheter without esophageal temperature monitoring.We investigated 70 consecutive patients who underwent point-by-point PVI without usage of ETP and who underwent esophago-gastro-duodenoscopy (EGD) with detailed evaluation of the esophagus after the index PVI procedure. The operator attempted to keep CF within the 10-40 g range. The incidences of esophageal lesions (EDEL) detected by endoscopy were then analyzed.Two of 70 patients (2.9%) showed EDEL consisting of one longitudinal ulcer-like erythematous lesion with fibrin and a different one consisting of a round-shaped lesion surrounded by erythema and petechial hemorrhage. All EDEL healed within two weeks under high proton-pump inhibitor therapy without developing AEF as proven by a second EGD of the esophagus.Point-by-point PVI without usage of ETP showed a low incidence of EDEL (2.9%); atrio-esophageal fistula was absent. Further studies on the necessity of ETP under CF control are necessary.

Surveillance colonoscopy in patients with inflammatory bowel disease: comparison of random biopsy vs. targeted biopsy protocols.

BACKGROUND: Endoscopic surveillance in patients with long-standing inflammatory bowel disease (IBD) improves early detection of intraepithelial neoplasia (IEN). We aimed to compare three different endoscopic surveillance strategies in the detection of IEN. METHODS: One hundred fifty surveillance colonoscopies (ulcerative colitis, UC n = 141; Crohn's disease, CD n = 9) were carried out. Random quadrant biopsies were taken (group I, n = 50). Chromoendoscopy with indigo carmine was performed and subsequently quadrant biopsies were collected (group II, n = 50). Patients in group III (n = 50) underwent confocal endomicroscopy (CEM), and CEM-guided as well as random quadrant biopsies were taken (group III, n = 50). The findings of CEM were correlated to conventional histology. Patients with high-grade IEN underwent surgery or strict follow-up by patients' request. RESULTS: In group I (1531 biopsies), no IEN was detected by histology. In group II (1,811 biopsies), chromoendoscopy-guided biopsies revealed high-grade IEN in two patients (4% detection rate). In four patients of group III (1477 biopsies), areas with high-grade IEN were clearly visible by CEM and confirmed by histology (8% detection rate, p < 0.05). Of six patients with high-grade IEN, five patients underwent proctocolectomy. Colorectal cancer was detected in one out of five patients. CONCLUSION: Targeted biopsy protocols guided by either chromoendoscopy or CEM led to higher detection rates of IEN and are thus mandatory for surveillance colonoscopies in patients with long-standing UC. Random biopsy protocols should be replaced by chromoendoscopy-guided protocols.