Risk Factors for Infectious Complications following Endoscopic Retrograde Cholangiopancreatography in Liver Transplant Patients: A Single-Center Study.

Background: Liver transplant recipients often require endoscopic retrograde cholangiopancreatography (ERCP) for biliary complications, which can lead to infections. This retrospective single-center study aimed to identify risk factors for infectious complications following ERCP in liver transplant patients. Methods: A retrospective analysis was conducted on 285 elective ERCP interventions performed in 88 liver transplant patients at a tertiary care center. The primary endpoint was the occurrence of an infection following ERCP. Univariable and multivariable regression analyses, Cox regression, and log-rank tests were employed to assess the influence of various factors on the incidence of infectious complications. Results: Among the 285 ERCP interventions, isolated anastomotic stenosis was found in 175 cases, ischemic type biliary lesion (ITBL) in 103 cases, and choledocholithiasis in seven cases. Bile duct interventions were performed in 96.9% of all ERCPs. Infections after ERCP occurred in 46 cases (16.1%). Independent risk factors for infection included male sex (OR 24.19), prednisolone therapy (OR 4.5), ITBL (OR 4.51), sphincterotomy (OR 2.44), cholangioscopy (OR 3.22), dilatation therapy of the bile ducts (OR 9.48), and delayed prophylactic antibiotic therapy (>1 h after ERCP) (OR 2.93). Additionally, infections following previous ERCP interventions were associated with an increased incidence of infections following future ERCP interventions (p < 0.0001). Conclusion: In liver transplant patients undergoing ERCP, male sex, prednisolone therapy, and complex bile duct interventions independently raised infection risks. Delayed antibiotic treatment further increased this risk. Patients with ITBL were notably susceptible due to incomplete drainage. Additionally, a history of post-ERCP infections signaled higher future risks, necessitating close monitoring and timely antibiotic prophylaxis.

Impact of dose escalation on colostomy-free survival and treatment outcome in squamous cell anal carcinoma.

PURPOSE: Primary radiochemotherapy (RCT) constitutes the standard of care for early- and advanced-stage anal carcinoma. This retrospective study investigates the impact of dose escalation on colostomy-free survival (CFS), overall survival (OS), locoregional control (LRC), progression-free survival (PFS), and acute and late toxicities in patients with squamous cell anal cancer. METHODS: Considered were the outcomes of 87 patients with anal cancer treated with radiation/RCT between May 2004 and January 2020 at our institution. Toxicities were evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE version 5.0). RESULTS: The 87 patients received treatment with a median boost of 63 Gy to the primary tumor. With a median follow-up of 32 months, the 3­year CFS, OS, LRC, and PFS were 79.5%, 71.4%, 83.9%, and 78.5%, respectively. Tumor relapse occurred in 13 patients (14.9%). Dose escalation to > 63 Gy (maximum 66.6 Gy) to the primary tumor in 38/87 patients revealed a nonsignificant trend for improved 3­year CFS (82.4% vs. 97%, P = 0.092), a significantly improved CFS for T2/T3 tumors (72.6% vs. 100%, P = 0.008), and a significantly improved 3­year PFS for T1/T2 tumors (76.7% vs. 100%, P = 0.035). While acute toxicities did not differ, dose escalation > 63 Gy led to a higher rate of chronic skin toxicities (43.8% vs. 69%, P = 0.042). Treatment with intensity-modulated radiotherapy (IMRT) showed a significant improvement in 3­year OS (75.4% vs. 53.8%, P = 0.048). In multivariate analysis, significant improvements for T1/T2 tumors (CFS, OS, LRC, PFS), G1/2 tumors (PFS), and IMRT (OS) were shown. The nonsignificant trend for CFS improvement with dose escalation > 63 Gy was also apparent in multivariate analysis (P = 0.067). CONCLUSION: Dose escalation > 63 Gy (maximum 66.6 Gy) may improve CFS and PFS for certain subgroups, with a concomitant increase in chronic skin toxicities. Modern IMRT seems to be associated with an improvement in OS.

Unmasking of Metamizole-induced Liver Injury by Simult aneous Development of Characteristic Agranulocytosis.

BACKGROUND: Metamizole is one of the most used analgesic, antipyretic, and spasmolytic agents in many countries worldwide. While metamizole-induced agranulocytosis is an, albeit seldom, well-known adverse event, metamizole-associated drug-induced liver injury has been reported rarely in the literature and hence often remains unconsidered. Here, we present a unique case where metamizole-induced hepatotoxicity got unmasked by the simultaneous development of characteristic agranulocytosis. CASE REPORT: A 22-year-old woman without known conditions presented with a new onset of fever, jaundice, and maculopapular rash and explicitly denied intake of any new substances. Laboratory tests showed liver injury, granulopenia, and positive anti-nuclear and anti-mitochondrial (AMA-M2) antibodies. Liver biopsy revealed a histological pattern characteristic of drug-induced liver injury and bone marrow biopsy, the classical picture of metamizole-induced agranulocytosis. Indeed the in-depth interview of the patient unveiled metamizole consumption over the last two months. Therefore, we could diagnose metamizole-induced hepato- and myelotoxicity. Accordingly, steroid therapy led to normalization of liver parameters and stimulation with granulocyte colony- stimulating factor to leukocyte recovery. CONCLUSION: This case report is intended to increase the awareness of metamizole-associated druginduced liver injury which should always be kept in mind due to its occasionally life-threatening course. Diagnosis can be difficult particularly if anamnesis and written records are without hints for prior metamizole intake.

Bowel Preparation With Polyethylene Glycol 3350 or Fasting Only Before Peroral Single-balloon Enteroscopy: A Randomized European Multicenter Trial.

BACKGROUND: Although bowel preparation before colonoscopy and capsule endoscopy is widely evaluated and usually follows established guidelines, a standard preparation regime for peroral small bowel enteroscopy is yet to be defined.The aim of the present study was to compare small bowel preparation with polyethylene glycol (PEG) and "fasting only" (FO) before peroral single-balloon enteroscopy (SBE). STUDY: We compared small bowel preparation with PEG versus "FO" for peroral SBE in a randomized European multicenter trial. Patients' and procedural characteristics were documented and carefully analyzed. Primary endpoint was the oral intubation depth of the small bowel. A modified Boston preparation scale was used to assess bowel cleansing as a secondary endpoint. RESULTS: In total, 43 patients were enrolled in this study (FO group: n=25; PEG group: n=18). In both groups, patients' characteristics were comparable. The indications for oral enteroscopy were equally distributed in both groups (P=0.894). The oral intubation depth was significantly higher in the PEG versus the FO group (261±87 vs. 203±66 cm; P=0.019; mean±SD), while the quality of bowel preparation was equally sufficient in both groups [complete visualization of the mucosa (Boston preparation scale) 83% versus 76% (P=1.000)]. CONCLUSIONS: Small bowel preparation with PEG for SBE yields significantly deeper intubation as compared with "FO" preparation. As patient comfort and safety was similar in both groups, PEG preparation might be favored, especially if deep intubation of the small bowel is desired. For patients requiring visualization of the proximal jejunum, a FO preparation seems to be sufficient.

Percutaneous-transhepatic-endoscopic rendezvous procedures are effective and safe in patients with refractory bile duct obstruction.

Background: Percutaneous-transhepatic-endoscopic rendezvous procedures (PTE-RVs) are rescue approaches used to facilitate biliary drainage. Objective: The objective of this article is to evaluate the safety and the technical success of PTE-RVs in comparison with those of percutaneous transhepatic cholangiographies (PTCs). Methods: Percutaneous procedures performed over a 10-year period were retrospectively analyzed in a single-center cohort. Examinations were performed because of a previous or expected failure of standard endoscopic methods including endoscopic retrograde cholangiography (ERC) or balloon-assisted ERC to achieve biliary access. Results: In total, 553 percutaneous procedures including 163 PTE-RVs and 390 PTCs were performed. Overall, 71.3% of the patients suffered from malignant disease with pancreas-carcinoma (32.8%) and cholangio-carcinoma (19.0%) as the most frequent, while 28.7% of the patients suffered from benign disease. Many patients had a postoperative change in bowel anatomy (50.8%).PTC had a higher technical success rate (89.7%); however, the technical success rate of PTE-RVs was still high (80.4%; p < 0.003). Overall complications occurred in 23.5% of all procedures. Significantly fewer complications occurred after performing PTE-RVs than after PTCs (16.6% vs 26.4%; p = 0.037). Conclusion: Beside a high technical efficacy of PTE-RVs, significantly fewer complications occur following PTE-RVs than following PTCs; thus, PTE-RV should be preferred over PTC alone in selected patients.

Esophageal and Mediastinal Lesions Following Multielectrode Duty-Cycled Radiofrequency Pulmonary Vein Isolation: Simple Equals Safe?

BACKGROUND: The development of esophageal lesions following atrial fibrillation (AF) ablation has frequently been reported. Mediastinal tissue layers and the posterior wall of the left atrium are in close proximity to the site of ablation. Hence, mucosal lesions might solely represent the "tip of the iceberg." We therefore investigated patients undergoing multielectrode phased radiofrequency (RF) ablation (PVAC®, Medtronic Inc., Minneapolis, MN, USA) for symptomatic AF by radial endosonography (EUS) in conjunction with conventional endoscopy esophago-gastro-duodenoscopy (EGD) to visualize potential mediastinal injuries following pulmonary vein isolation (PVI). METHODS AND RESULTS: Eighteen patients (six women, mean age 52.8 ± 12.8 years, range 32-72 years) underwent PVI using multielectrode phased RF ablation and EGD and EUS following PVI within 48 hours. Postablation periesophageal lesions were detected by EUS in 10 out of 18 patients (56%). Four out of 10 lesions consisted of mild changes like small pericardial effusions, whereas six out of 10 patients had more severe lesions of the mediastinum, including one patient with changes of the esophageal mucosa. No atrio-esophageal fistula developed during follow-up (FU; mean FU 215 ± 105 days). CONCLUSIONS: Mediastinal and esophageal structural changes occurred in a substantial number of patients. These findings highlight the necessity of close FU and the awareness of the potential development of an atrio-esophageal fistula also after multielectrode catheter ablation.

Prospective observational multicenter study to define a diagnostic algorithm for biliary candidiasis.

AIM: To develop an algorithm to improve the diagnosis and treatment of patients with biliary candidiasis. METHODS: We performed a prospective study of 127 patients who underwent endoscopic retrograde cholangiopancreatography, for various biliary disorders, at 3 tertiary referral centers in Germany from July 2011 through July 2012 (ClinicalTrials.gov: NCT01109550). Bile, buccal, and stool samples were collected. When indicated, endoscopic transpapillary bile duct biopsies were performed to clarify the etiology of bile duct strictures and to prove invasive fungal infections. RESULTS: Candida species were detected in 38 of the 127 bile samples (29.9%). By multivariate analysis patients' age and previous endoscopic sphincterotomy were independent risk factors for biliary candidiasis (P < 0.05). Patients with immunosuppression (P = 0.058) and recent long-term antibiotic therapy (> 7 d) (P = 0.089) tend to be at risk for biliary candidiasis. One patient was negative in mycological culture of bile fluid but invasive biliary candidiasis was diagnosed histologically. Of Candida subspecies detected, 36.7% were azole-resistant, such as C glabrata. Eight patients received anti-mycotic therapy, based on our algorithm. Of these, 3 had cancer with biliary tract involvement, 2 had secondary sclerosing cholangitis, 1 had retroperitoneal fibrosis, and 5 had septicemia. In all patients contamination was ruled out by smears of the endoscope channel. CONCLUSION: Gastroenterologists should be aware of frequent candida colonization in patients with cholangitis and biliary disorders. Our suggested algorithm facilitates the further clinical management.

Clearance of refractory bile duct stones with Extracorporeal Shockwave Lithotripsy: higher failure rate in obese patients.

OBJECTIVE: Bile duct stones that cannot be removed endoscopically are still a challenge in interventional gastroenterology. Extracorporeal shockwave lithotripsy (ESWL) with subsequent endoscopic extraction of residual fragments is an established treatment option if other endoscopic means are not successful. Our study aimed to investigate the efficacy and safety of ESWL for clearance of refractory bile duct stones. MATERIAL AND METHODS: A total of 73 consecutive patients treated for refractory choledocholithiasis with ESWL were retrospectively analyzed. Success and complication rates were calculated. RESULTS: Complete stone clearance was achieved in 66 cases (90%). Patients with complete clearance had a significantly lower body mass index or BMI (25.55 ± 5.01 kg/m² vs. 31.60 ± 6.26 kg/m², p = 0.035) and needed less ESWL treatments (3.61 ± 1.87 vs. 5.00 ± 1.63, p = 0.048). A relevant drop of hemoglobin occurred significantly more often in the group with partial clearance (43% vs. 6%, p = 0.005). CONCLUSIONS: ESWL proves to be an excellent clearing approach to refractory bile duct stones with high success rates. However, obesity is one risk factor for ESWL failure and higher procedural hazard.

Clinical outcome and predictors of survival after TIPS insertion in patients with liver cirrhosis.

AIM: To determine the clinical outcome and predictors of survival after transjugular intrahepatic portosystemic stent shunt (TIPS) implantation in cirrhotic patients. METHODS: Eighty-one patients with liver cirrhosis and consequential portal hypertension had TIPS implantation (bare metal) for either refractory ascites (RA) (n = 27) or variceal bleeding (VB) (n = 54). Endpoints for the study were: technical success, stent occlusion and stent stenosis, rebleeding, RA and mortality. Clinical records of patients were collected and analysed. Baseline characteristics [e.g., age, sex, CHILD score and the model for end-stage liver disease score (MELD score), underlying disease] were retrieved. The Kaplan-Meier method was employed to calculate survival from the time of TIPS implantation and comparisons were made by log rank test. A multivariate analysis of factors influencing survival was carried out using the Cox proportional hazards regression model. Results were expressed as medians and ranges. Comparisons between groups were performed by using the Mann-Whitney U-test and the χ2 test as appropriate. RESULTS: No difference could be seen in terms of age, sex, underlying disease or degree of portal pressure gradient (PPG) reduction between the ascites and the bleeding group. The PPG significantly decreased from 23.4 ± 5.3 mmHg (VB) vs. 22.1 ± 5.5 mmHg (RA) before TIPS to 11.8 ± 4.0 vs. 11.7 ± 4.2 after TIPS implantation (P = 0.001 within each group). There was a tendency towards more patients with stage CHILD A in the bleeding group compared to the ascites group (24 vs 6, P = 0.052). The median survival for the ascites group was 29 mo compared to > 60 mo for the bleeding group (P = 0.009). The number of radiological controls for stent patency was 6.3 for bleeders and 3.8 for ascites patients (P = 0.029). Kaplan-Meier calculation indicated that stent occlusion at first control (P = 0.027), ascites prior to TIPS implantation (P = 0.009), CHILD stage (P = 0.013), MELD score (P = 0.001) and those patients not having undergone liver transplantation (P = 0.024) were significant predictors of survival. In the Cox regression model, stent occlusion (P = 0.022), RA (P = 0.043), CHILD stage (P = 0.015) and MELD score (P = 0.004) turned out to be independent prognostic factors of survival. The anticoagulation management (P = 0.097), the porto-systemic pressure gradient (P = 0.460) and rebleeding episodes (P = 0.765) had no significant effect on the overall survival. CONCLUSION: RA, stent occlusion, initial CHILD stage and MELD score are independent predictors of survival in patients with TIPS, speaking for a close follow-up in these circumstances.

A typical presentation of a rare cause of obscure gastrointestinal bleeding.

A 52-year-old white woman had suffered from intermittent gastrointestinal (GI) bleeding for one year. Upper GI endoscopy, colonoscopy and peroral double-balloon enteroscopy (DBE) did not detect any bleeding source, suggesting obscure GI bleeding. However, in videocapsule endoscopy a jejunal ulceration without bleeding signs was suspected and this was endoscopically confirmed by another peroral DBE. After transfusion of packed red blood cells, the patient was discharged from our hospital in good general condition. Two weeks later she was readmitted because of another episode of acute bleeding. Multi-detector row computed tomography with 3D reconstruction was performed revealing a jejunal tumor causing lower gastrointestinal bleeding. The patient underwent exploratory laparotomy with partial jejunal resection and end-to-end jejunostomy for reconstruction. Histological examination of the specimen confirmed the diagnosis of a low risk gastrointestinal stromal tumor (GIST). Nine days after surgery the patient was discharged in good health. No signs of gastrointestinal rebleeding occurred in a follow-up of eight months. We herein describe the complex presentation and course of this patient with GIST and also review the current approach to treatment.

Long-term efficacy and safety of double balloon enteroscopy--prospective and retrospective data from a single center study.

OBJECTIVE: Double balloon enteroscopy (DBE) has evolved as one of the most innovative and fast spreading endoscopic procedures in the last decade. With increasing experience of performing endoscopic procedures in the mid gut outside the operating room it is necessary to investigate the effectiveness of DBE regarding therapeutic consequences, long-term efficacy as well as safety. MATERIAL AND METHODS: To address this we retrospectively analyzed all DBE performed over a period of 2 years at our department. Furthermore, in order to evaluate long-term effectiveness of DBE procedures we performed a follow-up analysis on all patients, whose DBE procedure was at least 6 months ago. In addition, 100 consecutive patients who underwent DBE were questioned regarding procedure associated complaints using a standardized questionnaire. RESULTS: Retrospective analysis of all DBE procedures performed in our department before November 2006 (n = 545) revealed an overall diagnostic yield of 39.7% and a therapeutic yield of 31.1%. The overall number of major complications accounted to 0.9%. Follow-up analysis revealed a long-term effect of endoscopic interventions in more than 50%, while in those patients with an initially negative DBE long-term follow-up only revealed symptom explaining findings in 17% with the majority of the other patients being asymptomatic during follow-up. Regarding patient related complaints the prospective analysis showed that DBE procedures in general are well tolerated with the most common complaint being meteorism. CONCLUSIONS: DBE showed to be a relatively safe and well tolerated procedure. However, more sensitive algorithms are needed to enhance the therapeutic results.

Damage to the esophagus after atrial fibrillation ablation: Just the tip of the iceberg? High prevalence of mediastinal changes diagnosed by endosonography.

BACKGROUND: Radiofrequency catheter ablation is increasingly used in the treatment of atrial fibrillation. Esophageal wall changes varying from erythema to ulcers have been described by endoscopy in up to 47% of patients following pulmonary vein isolation (PVI). Although esophageal changes are frequently reported, the development of a left atrial (LA)-esophageal fistula is fortunately rare. Nevertheless, mucosal changes may just represent "the tip of the iceberg." The aim of this study was, therefore, to investigate the more subtle changes of and injuries to the posterior wall of the LA, the periesophageal and mediastinal connective tissue, and the whole wall of the esophagus, including mucosal changes by esophagogastroduodenoscopy (EGD) combined with radial endosonography (EUS). METHODS AND RESULTS: Twenty-nine patients (7 females; mean age, 57.7+/-10.5 years [range, 23-75 years]) underwent EGD and EUS before and after PVI within 48 hours. PVI was performed as a circumferential antral isolation of the septal and lateral pulmonary veins guided by a decapolar circular mapping catheter using a 3-dimensional mapping system with the integration of a preprocedurally acquired computed tomography scan of the left atrium. The maximum power applied was 30 W, with an open-irrigated catheter using a maximum flow rate of 30 mL/min. In all patients, the esophagus was reconstructed using the same computed tomography scan and displayed during the ablation procedure. In case of newly detected periesophageal changes, EGD and EUS were repeated 1 week after the PVI. In all patients, a regular contact area between the LA and the esophagus could be demonstrated before PVI. The mean vertical contact length was 4.4+/-1.5 cm (range, 2-10 cm); and the mean distance between the anterior wall of the esophagus and the endocardium was 2.6+/-0.8 mm (range, 1.4-4.0 mm). After PVI, morphological changes of the periesophageal connective tissue and the posterior wall of the LA were diagnosed by endosonography in 8 patients (27%; 95% confidence interval, 12.73-47.24). No mucosal changes of the esophagus in terms of erythema or ulcers were found. In all but one patient (who refused the control), all periesophageal and atrial changes had resolved within 1 week. No atrioesophageal fistula occurred during follow-up (mean follow-up, 294+/-110 days [range, 36-431 days]). CONCLUSIONS: Mucosal changes of the esophagus after PVI-like ulcers or erythema could not be demonstrated, yet structural changes of the mediastinum, which were only visible by endosonography, occurred in 27% of patients in the present study. This may indicate a higher than expected periesophageal injury because of PV ablation. Endosonography might prove to be a sensitive and reliable tool in the follow-up after PVI.

Prevalence, associations, and trends of biliary-tract candidiasis: a prospective observational study.

BACKGROUND: Biliary obstruction and cholangitis are common problems in gastroenterology. Infections of the biliary tract with Candida and other fungal species have increasingly been seen in the last few years. OBJECTIVE: To investigate the prevalence, associations, and trends of biliary-tract candidiasis. DESIGN: A prospective, observational, diagnostic study. SETTING: University Hospital, Muenster, Germany. PATIENTS: Consecutive patients undergoing ERCP for various indications. RESULTS: In 54 of 123 patients, we found Candida species in bile samples (44%). In only 7 patients, candidiasis was suspected on endoscopy before mycologic proof. Only 4 of these 7 patients were correctly diagnosed with biliary candidiasis by simple morphologic aspects. The fungus was mainly differentiated as Candida albicans or Candida glabrata and rarely as Candida parapsilosis, Candida tropicalis, or other subspecies. Immunosuppression for various reasons was significantly associated with bile-duct candidiasis (P < .02). No significant association was found between positive fungal cultures and prior endoscopic sphincterotomy (P = .0824) or prior ERCP (P = .1152). Biliary candidiasis was neither associated with positive fungal cultures of buccal smears (P = .0722) nor with positive findings in stool samples (P = .0860). LIMITATIONS: Highly selected patient population. Buccal smears and stool samples were not obtained from all patients. Contamination artifacts cannot totally be excluded with the ERCP procedure. CONCLUSIONS: Candida species very frequently can be detected in the bile. Positive fungal cultures of bile samples are not just contamination artifacts. This has to be taken into account when designing an anti-infectious treatment for recurrent cholangitis or even more cholangiosepsis. Especially in immunosuppressed patients or recipients of long-term antibiotic therapy, physicians should screen for biliary-tract candidiasis during endoscopic examination.

Endoluminal gastroplasty (EndoCinch) versus endoscopic polymer implantation (Enteryx) for treatment of gastroesophageal reflux disease: 6-month results of a prospective, randomized trial.

OBJECTIVES: The aim of this study was to compare and determine the efficiency and safety of two newly introduced endoscopic antireflux procedures in the treatment of gastroesophageal reflux disease (GERD). METHODS: In a prospective, randomized trial, endoluminal gastroplasty (EndoCinch) was compared with polymer injection (Enteryx) employing 51 consecutive patients dependent on proton pump inhibitor therapy. Follow-up evaluation included drug consumption, symptoms, quality-of-life scoring, endoscopy, pH monitoring, manometry, and documentation of adverse events. RESULTS: Twenty-six patients were assigned to EndoCinch treatment, 23 patients received Enteryx implantation, and two patients dropped out before applying endoscopic therapy. At 6 months, proton pump inhibitor therapy could be stopped or dosage was reduced by > or =50% in 20 of 26 (77%) EndoCinch-treated patients and in 20 of 23 patients treated by Enteryx (87%, p= 0.365), which differed significantly in both groups compared to the pre-interventional status (p < 0.0001). Esophageal acid reflux (pH < 4) decreased from 14.5% to 9.6% in EndoCinch-treated patients (p= 0.071) and from 15.5% to 13.9% in patients treated by Enteryx (p= 0.930). Heartburn symptom score, modified DeMeester score, gastrointestinal life quality index, and SF-36 physical health survey score improved significantly in both groups postinterventionally (p < 0.0001). Approximately 25% of the patients in both groups required retreatment in an attempt to achieve symptom control. CONCLUSIONS: This is the first prospective, randomized study directly comparing two endoscopic anti-GERD techniques. EndoCinch and Enteryx seem to be equally successful in the treatment of GERD significantly reducing the proton pump inhibitor dosages, and also by improving symptoms of patients. Both endoluminal antireflux procedures may be promising therapeutic options; long-term evaluation will have to show if the positive initial results can be maintained.