Publications by authors named "Hauke Heinzow"

46 Publications

Refining prediction of survival after TIPS with the novel Freiburg index of post-TIPS survival.

J Hepatol 2021 Jan 25. Epub 2021 Jan 25.

Department of Medicine II, Medical Center University of Freiburg, Faculty of Medicine, University of Freiburg, Hugstetter Str. 55, 79106 Freiburg, Germany.

Background And Aim: TIPS implantation is an effective and safe treatment for complications of portal hypertension. Prediction of survival is important in these patients as they constitute a high-risk population per se. Therefore, the aim of our study was to develop an alternative prognostic model for accurate survival prediction after planned TIPS implantation.

Methods: A total of 1871 patients with de novo TIPS implantation for ascites or secondary prophylaxis of variceal bleeding were recruited retrospectively. The study cohort was divided in a training set (80% of study patients; n=1496) and a validation set (20% of study patients; n=375). Further, patients with early (preemptive) TIPS implantation due to variceal bleeding were included as another validation cohort (n=290). Medical data and overall survival (OS) were assessed. A Cox regression model was performed to create an alternative prediction model, which includes significant prognostic factors.

Results: Age, bilirubin, albumin and creatinine were the most important prognostic factors. These parameters were included in a new score named the Freiburg index of post-TIPS survival (FIPS). The FIPS score was able to identify high-risk patients with a significantly reduced prognosis of a median survival of 5.0 [3.1 - 6.9] months after TIPS implantation in the training set. These results were confirmed in the validation set (median survival of 3.1 [0.9 - 5.3] months). The FIPS score showed better prognostic discrimination compared to the Child-Pugh-, MELD-, MELD-Na-score and the bilirubin-platelet model. However, the FIPS score showed insufficient prognostic discrimination in patients with early TIPS implantation.

Conclusions: The FIPS score is superior to established scoring systems for identifying high-risk patients with a reduced prognosis in patients with elective TIPS implantation.
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http://dx.doi.org/10.1016/j.jhep.2021.01.023DOI Listing
January 2021

Bile Acids in Control of the Gut-Liver-Axis.

Z Gastroenterol 2021 Jan 11;59(1):63-68. Epub 2021 Jan 11.

Medizinische Klinik B (Gastroenterologie, Hepatologie, Endokrinologie, Klinische Infektiologie), Universitätsklinikum Münster, Munster, Germany.

The liver and gut share an intimate relationship whose communication relies heavily on metabolites, among which bile acids play a major role. Beyond their function as emulsifiers, bile acids have been recognized for their influence on metabolism of glucose and lipids as well as for their impact on immune responses. Therefore, changes to the composition of the bile acid pool can be consequential to liver and to gut physiology. By metabolizing primary bile acids to secondary bile acids, the bacterial gut microbiome modifies how bile acids exert influence. An altered ratio of secondary to primary bile acids is found to be substantial in many studies. Thus, disease pathogenesis and progression could be changed by gut microbiome modification which influences the bile acid pool.
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http://dx.doi.org/10.1055/a-1330-9644DOI Listing
January 2021

Evaluation of impact of elective invasive examinations in patients with transjugular intrahepatic portosystemic shunt in the long-term follow up.

Z Gastroenterol 2021 Jan 11;59(1):24-34. Epub 2021 Jan 11.

Medical Clinic B, Department of Gastroenterology, Hepatology, Endocrinology, Clinical Infectiology, University Hospital Muenster, Muenster, Germany.

Introduction:  In the management of patients with decompensated liver cirrhosis, transjugular intrahepatic portosystemic shunt (TIPS) insertion is well-established but common recommendations in the follow up management are inconsistent. Doppler sonography is commonly used for detection for TIPS dysfunction whilst data on the impact of elective invasive examinations are scarce.

Aim:  The aim of this retrospective analysis is to evaluate potential benefits of elective invasive examinations in the follow up management of patients after TIPS insertion METHODS:  Data of all patients receiving TIPS at the university hospitals of Muenster and Bonn between 2013 and 2018 (n = 534) were collected. The impact of performance of elective invasive examinations at 12 months after TIPS insertion on the occurrence of liver related events (LREs) and frequency of TIPS revisions within 24 months after TIPS insertion was analyzed.

Results:  No significant differences were found concerning occurrence of liver related events after 24 months depending on whether an elective invasive examination was performed. Occurrence of hepatic encephalopathy, relapse of initial indication for TIPS, as well as death or liver transplantation all did not differ. These findings were verified by a subgroup analysis including only patients who did not experience a LRE or TIPS revision within the first 12 months after TIPS procedure.

Conclusion:  The analyzed data suggest no evidence for a beneficial impact due to implementation of an elective invasive examination program after TIPS insertion. Invasive examinations should remain reserved to patients with suspected TIPS dysfunction.
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http://dx.doi.org/10.1055/a-1330-9867DOI Listing
January 2021

Standard versus Endocuff versus cap-assisted colonoscopy for adenoma detection: A randomised controlled clinical trial.

United European Gastroenterol J 2021 Feb 16. Epub 2021 Feb 16.

Department of Medicine 1, Klinikum Ibbenbueren, Teaching Hospital University of Muenster, Münster, Germany.

Background And Aims: Adenoma detection rate (ADR) in colon cancer screening is most important for cancer prophylaxis. This work is the first three-armed randomised controlled clinical trial aimed at comparing a head-to-head setting standard colonoscopy (SC) with Endocuff-assisted colonoscopy (EC) and cap-assisted colonoscopy (CAC) for improvement of ADR.

Methods: Patients from Poland and Germany with independent indication for colonoscopy were randomised into three arms of this trial: EC, CAC and SC. Exclusion criteria were age <18 years, active Crohn's disease or ulcerative colitis, known stenosis and post-colonic resection status.

Results: A total of 585 patients (195 SC, 189 EC and 186 CAC) were enrolled in this study. Indications were not different between the groups (colorectal cancer screening 51%, diagnostic colonoscopy in 31% and post-polypectomy follow-up in 18%; p = 0.94). Withdrawal time was a mean of 7 min in all groups (p = 0.658), and bowel preparation did not differ between the groups. The time to reach the caecum was significantly reduced when using the cap (a mean of 6 min for CAC vs. 7 min for SC; p = 0.0001). There was no significant difference in the primary outcome of the ADR between the groups (EC 32%, CAC 30%, SC 30%; p = 0.815). EC proved to be superior (EC vs. SC) in the sigmoid colon and transverse colon for polyp detection.

Conclusion: The use of EC increased the total number of polyps seen during colonoscopy. In contrast to recent studies, no significant improvement of the ADR was detected.
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http://dx.doi.org/10.1177/2050640620982952DOI Listing
February 2021

Shunt-Induced Hepatic Encephalopathy in TIPS: Current Approaches and Clinical Challenges.

J Clin Med 2020 Nov 23;9(11). Epub 2020 Nov 23.

Institute of Clinical Radiology, University Hospital Muenster, D-48149 Muenster, Germany.

Transjugular intrahepatic portosystemic shunt (TIPS) is an established treatment tool in decompensated liver cirrhosis that has been shown to prolong transplant-free survival. Hepatic encephalopathy (HE) is a frequent complication of decompensated cirrhosis, eventually induced and/or aggravated by TIPS, that remains a clinical challenge especially in these patients. Therefore, patient selection for TIPS requires careful assessment of risk factors for HE. TIPS procedural parameters regarding stent size and invasive portosystemic pressure gradient measurements thereby have an important role. Endovascular shunt modification, in combination with a conservative medical approach, often results in a significant reduction of symptoms. This review summarizes HE molecular mechanisms and pathophysiology as well as diagnostic and therapeutic approaches targeting shunt-induced HE.
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http://dx.doi.org/10.3390/jcm9113784DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7700586PMC
November 2020

First-In-Class CD13-Targeted Tissue Factor tTF-NGR in Patients with Recurrent or Refractory Malignant Tumors: Results of a Phase I Dose-Escalation Study.

Cancers (Basel) 2020 Jun 7;12(6). Epub 2020 Jun 7.

Department of Medicine A, Hematology, Oncology, University Hospital Muenster, D-48149 Muenster, Germany.

Background: Aminopeptidase N (CD13) is present on tumor vasculature cells and some tumor cells. Truncated tissue factor (tTF) with a C-terminal NGR-peptide (tTF-NGR) binds to CD13 and causes tumor vascular thrombosis with infarction.

Methods: We treated 17 patients with advanced cancer beyond standard therapies in a phase I study with tTF-NGR (1-h infusion, central venous access, 5 consecutive days, and rest periods of 2 weeks). The study allowed intraindividual dose escalations between cycles and established Maximum Tolerated Dose (MTD) and Dose-Limiting Toxicity (DLT) by verification cohorts.

Results: MTD was 3 mg/m tTF-NGR/day × 5, q day 22. DLT was an isolated and reversible elevation of high sensitivity (hs) Troponin T hs without clinical sequelae. Three thromboembolic events (grade 2), tTF-NGR-related besides other relevant risk factors, were reversible upon anticoagulation. Imaging by contrast-enhanced ultrasound (CEUS) and dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) showed major tumor-specific reduction of blood flow in all measurable lesions as proof of principle for the mode of action of tTF-NGR. There were no responses as defined by Response Evaluation Criteria in Solid Tumors (RECIST), although some lesions showed intratumoral hemorrhage and necrosis after tTF-NGR application. Pharmacokinetic analysis showed a t of 8 to 9 h without accumulation in daily administrations.

Conclusion: tTF-NGR is safely applicable with this regimen. Imaging showed selective reduction of tumor blood flow and intratumoral hemorrhage and necrosis.
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http://dx.doi.org/10.3390/cancers12061488DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7352358PMC
June 2020

A prospective, multicentre study in acute non-cirrhotic, non-malignant portal vein thrombosis: comparison of medical and interventional treatment.

Aliment Pharmacol Ther 2020 07 7;52(2):329-339. Epub 2020 Jun 7.

Freiburg, Germany.

Background: To evaluate medical versus interventional treatment (transjugular thrombus fragmentation, local thrombolysis with or without stent implantation) in patients with acute non-cirrhotic, non-malignant portal vein thrombosis (PVT).

Methods: This prospective, observational study enrolled 65 patients with acute (<28 days since begin of symptoms, no cavernoma) PVT in nine centres. Thirty patients received medical treatment and 35 patients received interventional treatment. PVT was graded into grade 1: short thrombosis and incomplete occlusion of the vessel lumen and grade 2: extended thrombosis or complete occlusion. Treatment response was classified as partial or complete, if thrombosis was reduced by one grade or to <25% of the vessel diameter respectively.

Results: Partial and complete response rates were 7% and 30% in the medical compared to 17% and 54% (P < 0.001) in the interventional treatment group. In the multivariate analysis, interventional treatment showed a strong positive (OR 4.32, P < 0.016) and a myeloproliferative aetiology a negative (OR 0.09, P = 0.006) prediction of complete response. Complications were rare in the medical group and consisted of septicaemia and upper gastrointestinal bleeding of unknown origin in one patient each. Interventional treatment was accompanied by mild and self-limiting bleeding complications in nine patients, moderate intra-abdominal bleeding requiring transfusions (2 units) in one patient and peritoneal bleeding requiring surgical rescue in one patient. Four patients in each group developed intestinal gangrene requiring surgery. One patient died 52 days after unsuccessful interventional treatment.

Conclusions: Compared to medical treatment alone, interventional treatment doubled response rates at the cost of increased bleeding complications.
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http://dx.doi.org/10.1111/apt.15811DOI Listing
July 2020

TIPS Modification in the Management of Shunt-Induced Hepatic Encephalopathy: Analysis of Predictive Factors and Outcome with Shunt Modification.

J Clin Med 2020 Feb 19;9(2). Epub 2020 Feb 19.

Institute of Clinical Radiology, University Hospital Muenster, D-48149 Muenster, Germany.

Purpose: To evaluate predictive parameters for the development of Hepatic Encephalopathy (HE) after Transjugular Intrahepatic Portosystemic Shunt (TIPS) placement and for success of shunt modification in the management of shunt-induced HE.

Methods: A retrospective analysis of all patients with TIPS ( = 344) has been performed since 2011 in our university liver center. = 45 patients with HE after TIPS were compared to = 48 patients without HE after TIPS (case-control-matching). Of = 45 patients with TIPS-induced HE, = 20 patients received a reduction stent ( = 18) or TIPS occlusion ( = 2) and were differentiated into responders (improvement by at least one HE grade according to the West Haven classification) and non-responders (no improvement).

Results: Older patient age, increased serum creatinine and elevated International Normalized Ratio (INR) immediately after TIPS placement were independent predictors for the development of HE. In 11/20 patients (responders, 55%) undergoing shunt modification, the HE grade was improved compared with nine non-responders (45%), with no relevant recurrence of refractory ascites or variceal bleeding. A high HE grade after TIPS insertion was the only positive predictor of treatment response ( = 0.019). A total of 10/11 responders (91%) survived the 6 months follow-up after modification but only 6/9 non-responders (67%) survived.

Discussion: Older patient age as well as an increased serum creatinine and INR after TIPS are potential predictors for the development of HE. TIPS reduction for the treatment of TIPS-induced HE is safe, with particular benefit for patients with pronounced HE.
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http://dx.doi.org/10.3390/jcm9020567DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7073830PMC
February 2020

Cytomegalovirus Viremia after Living and Deceased Donation in Kidney Transplantation.

J Clin Med 2020 Jan 17;9(1). Epub 2020 Jan 17.

Department of Medicine D, Division of General Internal Medicine, Nephrology and Rheumatology, University Hospital of Muenster, 48149 Muenster, Germany.

Despite screening, effective anti-viral drugs and risk-balanced prophylaxis, cytomegalovirus (CMV) remains a major cause of morbidity in transplant patients. The objective of this study was to retrospectively analyze the risk factors associated with CMV viremia after kidney transplantation in a large European cohort with standardized valganciclovir prophylaxis in the present era. A special focus was placed on the comparison of living and postmortal donation. We conducted a longitudinal observational study involving 723 adult patients with a total of 3292 patient-years who were transplanted at our center between 2007 and 2015. Valganciclovir prophylaxis was administered over 100 days for CMV+ donors (D) or recipients (R), over 200 days for D+/R-, and none in D-/R-. A CMV+ donor, rejection episodes, and deceased donor transplantation were identified to be associated with increased incidences of CMV viremia. Although we did not find a reduced overall survival rate for patients with CMV viremia, it was associated with worse graft function. Since we observed a relevant number of CMV infections despite prescribing valganciclovir prophylaxis, a pre-emptive strategy in patients with (suspected) adherence restrictions could be favored. Our data can help transplant physicians educate their patients about their individual CMV risk and choose the most appropriate CMV treatment approach.
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http://dx.doi.org/10.3390/jcm9010252DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7019428PMC
January 2020

Inflammation, etiologies and Model for End-stage Liver Disease score: What makes liver disease patients susceptible to developing colorectal neoplasia?

Hepatol Res 2020 Mar 17;50(3):342-352. Epub 2020 Jan 17.

Department of Gastroenterology and Hepatology, University Hospital Münster, Albert-Schweitzer-Campus 1, Münster, Germany.

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http://dx.doi.org/10.1111/hepr.13463DOI Listing
March 2020

Escalating interventional recanalization therapy in non-cirrhotic, non-malignant acute portal vein thrombosis.

Eur J Gastroenterol Hepatol 2019 Dec;31(12):1584-1591

Institute of Clinical Radiology, University Hospital Münster, Münster, Germany.

Objective: To evaluate the effectiveness of interventional therapy in acute, non-malignant, non-cirrhotic portal vein thrombosis.

Methods: We present a retrospective study of eight consecutive patients who presented with an acute non-malignant, non-cirrhotic portal vein thrombosis and were treated by mechanical recanalization using an escalating scheme including local aspiration, thrombolysis, rheolysis and the implantation of transjugular intrahepatic portosystemic shunt or other visceral stents.

Results: Recanalization rates applying the escalating scheme were good, with a success rate of 75%. However, major complications occurred in 50% of patients, mostly due to bleeding at the percutaneous access site, and minor complications in 12.5% of patients.

Conclusion: Interventional therapy is effective in acute portal vein thrombosis, but should only be performed at specialized centers and based on an individual treatment decision.
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http://dx.doi.org/10.1097/MEG.0000000000001559DOI Listing
December 2019

Endoscopic Radiofrequency Ablation Prolongs Survival of Patients with Unresectable Hilar Cholangiocellular Carcinoma - A Case-Control Study.

Sci Rep 2019 09 23;9(1):13685. Epub 2019 Sep 23.

Department of Medicine B for Gastroenterology and Hepatology, University Hospital Muenster, Muenster, Germany.

The life expectancy of unresectable hilar cholangiocellular carcinomas (CCCs) is very limited and endoscopic radiofrequency ablation (ERFA) of the biliary tract may prolong survival. Our single-center-study retrospectively analysed all CCC cases, in whom ERFAs of the biliary tract were performed between 2012 and 2017 and compared these to historical control cases who received the standard treatment of sole stent application. ERFA was performed in 32 patients with malignant biliary strictures that were mainly caused by Bismuth III and IV hilar CCCs (66%). 14 of these patients received repeated ERFAs, for an overall performance of 54 ERFAs. Stents were applied after examination of all patients (100%). Adverse events occurred in 18.5% of examinations. Case-control analysis revealed that the survival time of cases with unresectable Bismuth type III and IV hilar CCCs (n = 20) treated with combined ERFA and stent application significantly increased compared to controls (n = 22) treated with sole stent application (342 +/- 57 vs. 221 +/- 26 days; p = 0.046). In conclusion, ERFA therapy significantly prolonged survival in patients with unresectable Bismuth type III and IV hilar CCC. As an effective and safe method, ERFA should be considered as a palliative treatment for all these patients.
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http://dx.doi.org/10.1038/s41598-019-50132-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6757045PMC
September 2019

[The Clif-Consortium strikes again: Multidrug-resistant bacterial infections in patients with decompensated cirrhosis and with acute-on-chronic liver failure in Europe].

Z Gastroenterol 2019 08 9;57(8):997-999. Epub 2019 Aug 9.

Medizinische Klinik B für Gastroenterologie und Hepatologie, Universitätsklinikum Münster.

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http://dx.doi.org/10.1055/a-0945-0607DOI Listing
August 2019

Chronic liver disease promotes lesions of the colorectal adenoma-carcinoma sequence, independent of liver cirrhosis.

United European Gastroenterol J 2019 06 21;7(5):662-672. Epub 2019 Jan 21.

Department of Gastroenterology and Hepatology, University Hospital Münster, Münster, Germany.

Background: Research increasingly focuses on identifying individuals at greater risk of colorectal cancer (CRC) to enhance colonoscopy screening efficacy.

Objective: The objective of this article is to determine associations between chronic liver disease and lesions along the colorectal adenoma-carcinoma sequence.

Methods: This retrospective study encompasses consecutive liver disease patients (LDPs) of all etiologies evaluated for liver transplantation at a single institution and a control group of liver-healthy patients (LHPs) undergoing colonoscopy as part of the German CRC screening program.Rates of polyps, adenomas, high-risk situations (HRS) and CRC were analyzed in univariable and multivariable settings adjusting for age, gender, body mass index and number of colonoscopies. Differences between LHPs and LDPs and between cirrhotic and noncirrhotic hepatopathy were assessed.

Results: In total, 1046 patients (52.6% male, median age 59.6 years) were included, of whom 38.9% had liver disease. A total of 41.0% of all patients showed polyps, 23.2% adenomas, 10.0% HRS, and 0.5% CRC. LDPs were more likely to develop polyps, adenomas and HRS than LHPs, both in univariable and multivariable analysis. There were no significant differences between cirrhotic and noncirrhotic patients.

Conclusion: Chronic liver disease of any etiology is associated with colonic lesions of the colorectal adenoma-carcinoma sequence, independent of cirrhosis. LDPs should receive intensified, and earlier, colonoscopy screening.
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http://dx.doi.org/10.1177/2050640619826391DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6545718PMC
June 2019

Pictorial Representation of Illness and Self Measure (PRISM): A Novel Visual Instrument to Quantify Suffering in Liver Cirrhosis Patients and Liver Transplant Recipients.

Ann Transplant 2018 Sep 28;23:674-680. Epub 2018 Sep 28.

Department of Gastroenterology and Hepatology, Münster University Hospital, Münster, Germany.

BACKGROUND The level of suffering of chronically ill patients does not necessarily correlate with illness severity. In this study, we evaluated the burden of suffering and its impact on health-related quality of life in liver transplant recipients and liver cirrhosis patients. MATERIAL AND METHODS The Pictorial Representation of Illness and Self Measure (PRISM) was used to explore levels of suffering in outpatients of Münster University Hospital, Germany. Self-illness separation scores were analyzed as a measure of disease-specific burden of suffering. Health-related quality of life was measured using the Short Form Health Survey (SF-36). RESULTS Data from 201 subjects were statistically analyzed. Median Self-illness separation scores for liver transplant recipients and patients with liver cirrhosis were 13.5 (minimum/maximum: 0.2/25.6) cm and 6.3 (0.1/25.6) cm (p<0.001), respectively. The median SF-36 Mental Component Summary and Physical Component Summary scores were 46.4 (12.5/66.2) and 40.1 (12.3/61.1), respectively. Higher health-related quality of life was associated with greater self-illness separation. Liver transplant recipients showed normal Mental Component Summary scores compared with the general German population; patients with liver cirrhosis had significantly lower Mental Component Summary scores. Physical Component Summary scores were significantly higher in liver transplant recipients than in patients with liver cirrhosis, but still lower than in the general population. CONCLUSIONS PRISM is a novel, simple tool for measuring the illness burden in liver transplant recipients and patients with liver cirrhosis. This measure may help to identify patients at a higher risk of psychological disorders.
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http://dx.doi.org/10.12659/AOT.910278DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6248009PMC
September 2018

Impact of direct-acting antiviral therapy on the need for liver transplantation related to hepatitis C in Germany.

J Hepatol 2018 10 6;69(4):982-984. Epub 2018 Aug 6.

Department of Gastroenterology and Hepatology, University Hospital Essen, University of Duisburg Essen, Germany; Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany; Leberstiftungs-GmbH Deutschland, Hannover, Germany; German Center for Infection Research (DZIF), Hannover-Braunschweig Site, Germany; Helmholtz Center for Infection Research (HZI), Braunschweig, Germany.

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http://dx.doi.org/10.1016/j.jhep.2018.07.001DOI Listing
October 2018

Digital single-operator cholangioscopy: a useful tool for selective guidewire placements across complex biliary strictures.

Surg Endosc 2019 03 13;33(3):731-737. Epub 2018 Jul 13.

Department of Medicine B for Gastroenterology and Hepatology, University Hospital Muenster, Albert-Schweitzer-Campus 1, 48149, Muenster, Germany.

Background: Treatment of biliary strictures is challenging. Digital single-operator cholangioscopes (SOCs) equipped with an improved imaging quality, were recently introduced and may be useful for selective guidewire placement in difficult biliary strictures.

Methods: A total of 167 digital SOC procedures performed between 2015 and 2018 were retrospectively analyzed for successful guidewire placements across biliary strictures. Only cases with previous failed conventional guidewire placement approaches were included.

Results: In total, 30 examinations with a digital SOC-assisted guidewire placement across biliary strictures, performed in 23 patients, were identified. In 52% of all patients, the stricture was benign with post-liver-transplant strictures (75%) as the most frequent finding; in 48% of all patients the stricture was malignant with cholangiocellular carcinoma as the most frequent type (64%). Guidewire placement was successful in 21 of 30 procedures (70%). According to a subgroup analysis, digital SOC-assisted guidewire placements were significantly more successful in patients with benign strictures than those in patients with malignant strictures (88.2% vs. 46.2%; p = 0.02). Furthermore, the technical success rate tended to be increased in cases of initial examinations (78.3%) than in patients with repeated examinations (42.9%; p = 0.15). Adverse events, such as post-interventional pancreatitis or cholangitis as well as severe bleeding occurred in 16.7% of all examinations.

Conclusions: Digital SOC-assisted guidewire placements have high technical success rates, especially in benign biliary strictures. This technique can help to avoid more invasive procedures such as percutaneous transhepatic or endoscopic ultrasound-guided biliary drainage.
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http://dx.doi.org/10.1007/s00464-018-6334-6DOI Listing
March 2019

Novel score predicts risk for cytomegalovirus infection in ulcerative colitis.

J Clin Virol 2018 08 9;105:103-108. Epub 2018 Jun 9.

Department of Medicine B, Gastroenterology and Hepatology, University Hospital Münster, Münster, Germany.

Background: Cytomegalovirus (CMV) infection is associated with relapse and exacerbation of ulcerative colitis (UC), especially in immunosuppressed patients.

Objectives: The aim of this study was to identify risk factors for CMV colitis and to develop a predictive risk score to estimate the probability of CMV colitis in UC patients supporting clinical decision making.

Study Design: A cohort of 239 UC-patients was retrospectively analyzed. Univariate and multivariate regression analysis identified several independent risk factors for CMV colitis and a predictive risk score was established using ROC analysis.

Results: CMV colitis is common in patients with severe ulcerative colitis. Clinical UC activity, disease duration and extent as well as the use of steroids and anti-TNF-α agents were identified as risk factors (p < 0.05 each). Based on five predictive parameters, a web-based risk score was developed. A strong correlation between the predicted and actual rates of CMV colitis was found (AUC: 0.855; 95% CI 0.79-0.92; p < 0.0001).

Conclusions: Our study supports the pathogenic relevance of CMV in UC. The predictive risk score estimates the risk of CMV colitis and might aid in clinical decision making, especially when timely modifications of therapeutic regimens are needed and reliable diagnostic tools are not readily available.
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http://dx.doi.org/10.1016/j.jcv.2018.06.002DOI Listing
August 2018

Preoperative prediction of curative surgery of perihilar cholangiocarcinoma by combination of endoscopic ultrasound and computed tomography.

United European Gastroenterol J 2018 Mar 25;6(2):263-271. Epub 2017 May 25.

Department of Transplant Medicine, University of Münster, Münster, Germany.

Background: Perihilar cholangiocarcinomas are often considered incurable. Late diagnosis is common. Advanced disease therefore frequently causes questioning of curative surgical outcome.

Aim: This study aimed to develop a prediction model of curative surgery in patients suffering from perihilar cholangiocarcinomas based on preoperative endosonography and computer tomography.

Methods: A cohort of 81 patients (median age 67 (54-75) years, 62% male) with perihilar cholangiocarcinoma was retrospectively analyzed. Multivariate logistic regression analysis of staging variables taken from the European Staging System was performed and applied to ROC analysis.

Results: The correlation of predicted rates of eligibility for surgery with actual rates reached AUC values between 0.652 and 0.758 for endosonography and computer tomography ( < 0.05 each). Best prediction for curative surgical option was achieved by combining endosonography and computer tomography (AUC: 0.787; 95% CI 0.680-0.893,  < 0.0001). A predictive model (pSurg) was developed using multivariate analysis.

Conclusions: Our predictive web-based model pSurg with inclusion of T, N, M, B, PV, HA and V stage of the recently published European Staging System for perihilar cholangiocarcinoma results in highly significant predictability for curative surgery when combining preoperative endosonography and computer tomography, thus allowing for better patient selection in terms of possibility of curative surgery.
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http://dx.doi.org/10.1177/2050640617713651DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5833220PMC
March 2018

Risk factors for allograft failure in liver transplant recipients.

Z Gastroenterol 2018 07 16;56(7):745-751. Epub 2018 Jan 16.

University Hospital Muenster, Department of Medicine B, Gastroenterology and Hepatology, Muenster, Germany.

Background: With regard to quality of life and organ shortage, follow-up after liver transplantation (LT) should consider risk factors for allograft failure in order to avoid the need for re-LT and to improve the long-term outcome of recipients. Therefore, the aim of this study was to explore potential risk factors for allograft failure after LT.

Material And Methods: A total of 489 consecutive LT recipients who received follow-up care at the University Hospital of Muenster were included in this study. Database research was performed, and patient data were retrospectively reviewed. Risk factors related to donor and recipient characteristics potentially leading to allograft failure were statistically investigated using binary logistic regression analysis. Graft failure was determined as graft cirrhosis, need for re-LT because of graft dysfunction, and/or allograft-associated death.

Results: The mean age of recipients at the time of LT was 50.3 ± 12.4 years, and 64.0 % were male. The mean age of donors was 48.7 ± 15.5 years. Multivariable statistical analysis revealed male recipient gender (p = 0.04), hepatitis C virus infection (HCV) (p = 0.014), hepatocellular carcinoma (HCC) (p = 0.03), biliary complications after LT (p < 0.001), pretransplant diabetes mellitus (p = 0.03), and/or marked fibrosis in the initial protocol biopsy during follow-up (p = 0.001) to be recipient-related significant and independent risk factors for allograft failure following LT.

Conclusion: Male recipients, patients who received LT for HCV or HCC, those with pretransplant diabetes mellitus, and LT recipients with biliary complications are at high risk for allograft failure and thus should be monitored closely.
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http://dx.doi.org/10.1055/s-0043-125225DOI Listing
July 2018

Commentary: Severe Sequelae to Mold-Related Illness As Demonstrated in Two Finnish Cohorts.

Front Immunol 2017 7;8:1694. Epub 2017 Dec 7.

Department of Environmental Health Protection, State Office for Social Services, Kiel, Germany.

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http://dx.doi.org/10.3389/fimmu.2017.01694DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5725433PMC
December 2017

Cost-Effectiveness of Access Expansion to Treatment of Hepatitis C Virus Infection Through Primary Care Providers.

Gastroenterology 2017 12 23;153(6):1531-1543.e2. Epub 2017 Oct 23.

School of Public Health, Department of Health Management and Policy, University of Michigan, Ann Arbor, Michigan.

Background & Aims: Chronic hepatitis C virus (HCV) infection is a major burden on individuals and health care systems. The Extension for Community Healthcare Outcomes (Project ECHO) enables primary care providers to deliver best-practice care for complex conditions to underserved populations. The US Congress passed the ECHO Act in late 2016, requiring the Department of Health and Human Services to investigate the model. We performed a cost-effectiveness analysis to assess diagnosis and treatment of HCV infection in a primary care patient panel with and without the implementation of Project ECHO.

Methods: We used Markov models to simulate disease progression, quality of life, and life expectancy among individuals with HCV infection and for the general population. Data from the University of New Mexico's ECHO operation for HCV show an increase in treatment rates. Corresponding increases in survival, quality-adjusted life years (QALYs), costs, and resulting budget impact between ECHO and non-ECHO patients with HCV were then compared.

Results: Project ECHO increased costs and QALYs. The incremental cost-effectiveness ratio of ECHO was $10,351 per QALY compared with the status quo; >99.9% of iterations fell below the willingness-to-pay threshold of $100,000 per QALY. We were unable to confirm whether the increase in rates of treatment associated with Project ECHO were due to increased or more targeted screening, higher adherence, or access to treatment. Our sensitivity analyses show that the results are largely independent of the cause. Budget impact analysis shows payers would have to invest an additional $339.54 million over a 5-year period to increase treatment by 4446 patients, per 1 million covered lives.

Conclusion: Using a simulated primary care patient panel, we showed that Project ECHO is a cost-effective way to find and treat patients with HCV infection at scale using existing primary care providers. This approach could substantially reduce the burden of chronic HCV infection in the United States, but high budgetary costs suggest that incremental rollout of ECHO may be best.
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http://dx.doi.org/10.1053/j.gastro.2017.10.016DOI Listing
December 2017

Single-operator cholangioscopy for biliary complications in liver transplant recipients.

World J Gastroenterol 2017 Jun;23(22):4064-4071

Anna Hüsing-Kabar, Hauke Sebastian Heinzow, Hartmut Hans-Jürgen Schmidt, Carina Stenger, Christian Wilms, Iyad Kabar, Department of Transplant Medicine, University Hospital Muenster, 48149 Muenster, Germany.

Aim: To evaluate cholangioscopy in addition to endoscopic retrograde cholangiopancreatography (ERCP) for management of biliary complications after liver transplantation (LT).

Methods: Twenty-six LT recipients with duct-to-duct biliary reconstruction who underwent ERCP for suspected biliary complications between April and December 2016 at the university hospital of Muenster were consecutively enrolled in this observational study. After evaluating bile ducts using fluoroscopy, cholangioscopy using a modern digital single-operator cholangioscopy system (SpyGlass DS™) was performed during the same procedure with patients under conscious sedation. All patients received peri-interventional antibiotic prophylaxis and bile was collected during the intervention for microbial analysis and for antibiotic susceptibility testing.

Results: Thirty-three biliary complications were found in a total of 22 patients, whereas four patients showed normal bile ducts. Anastomotic strictures were evident in 14 (53.8%) patients, non-anastomotic strictures in seven (26.9%), biliary cast in three (11.5%), and stones in six (23.1%). A benefit of cholangioscopy was seen in 12 (46.2%) patients. In four of them, cholangioscopy was crucial for selective guidewire placement prior to planned intervention. In six patients, biliary cast and/or stones failed to be diagnosed by ERCP and were only detectable through cholangioscopy. In one case, a bile duct ulcer due to fungal infection was diagnosed by cholangioscopy. In another case, signs of bile duct inflammation caused by acute cholangitis were evident. One patient developed post-interventional cholangitis. No further procedure-related complications occurred. Thirty-seven isolates were found in bile. Sixteen of these were gram-positive (43.2%), 12 (32.4%) were gram-negative bacteria, and Candida species accounted for 24.3% of all isolated microorganisms. Interestingly, only 48.6% of specimens were sensitive to prophylactic antibiotics.

Conclusion: Single-operator cholangioscopy can provide important diagnostic information, helping endoscopists to plan and perform interventional procedures in LT-related biliary complications.
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http://dx.doi.org/10.3748/wjg.v23.i22.4064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5473125PMC
June 2017

Successful Anti-HCV Therapy of a Former Intravenous Drug User with Sofosbuvir and Daclatasvir in a Peritranspant Setting: A Case Report.

Am J Case Rep 2016 Aug 24;17:605-10. Epub 2016 Aug 24.

Department of Transplantation Medicine, University Hospital Münster, Münster, Germany.

BACKGROUND Direct-acting antivirals (DAAs) represent a new hallmark in antiviral therapy of hepatitis C virus (HCV). DAAs have been shown to be safe and effective after liver transplantation (LT), but there is little information about their use in peritransplant settings. Former intravenous drug users represent an increasing group seeking HCV treatment. This case report demonstrates the successful peritransplant antiviral treatment of a former intravenous drug user who had been treated in a methadone maintenance program. CASE REPORT The patient was diagnosed with Child B cirrhosis for the first time in 2009. He had a Model for End-stage Liver Disease (MELD) score of 21 and started antiviral therapy with sofosbuvir (SOF) and daclatasvir (DCV) in March 2014. Due to hepatic decompensation, he received a LT in April 2014. Immunosuppression was performed with tacrolimus (TAC) and mycophenolate-mofetil (MMF), and boosted with prednisolone in the initial stage. Four weeks after his LT, the patient presented with an acute renal injury. The patient was discharged one week later after sufficient hydration, discontinuation of non-steroidal anti-phlogistics therapy, and adjustments to his immunosuppressive regimen. At the beginning of his therapy, the number of RNA copies was 13,000 IU/mL. He received 24 weeks of anti-HCV treatment with SOF and DCV; the antiviral treatment was successful and his LT was well tolerated.  CONCLUSIONS Treatment of HCV is feasible in a peritransplant setting. The antiviral regimen we used did not seem to have any relevant interactions with the patient's immunosuppressive regimens. Still, the peritransplant setting is a very demanding environment for anti-HCV therapy, and further studies are needed.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4999016PMC
http://dx.doi.org/10.12659/ajcr.895839DOI Listing
August 2016

[Acute liver failure after ingestion of death cap mushrooms].

Dtsch Med Wochenschr 2016 Jul 30;141(13):940-2. Epub 2016 Jun 30.

Amatoxins, which are mainly found in Amanita phalloides, Amanita virosa, and Galerina autumnalis, are responsible for the majority of fatal intoxication with green death cap. The intoxication is associated with acute liver failure, which explains the poor prognosis. Acute liver injury is generally preceeded by a gastrointestinal phase with nausea, vomiting and diarrhea. In the course, pre-renal kidney failure due to the associated fluid deficit and fulminant liver failure may occur. General guidelines for the treatment of amatoxin poisoning are yet not available. We report on three patients who suffered from amatoxin mushroom poisoning after ingestion of green death cap mushrooms. Based on the pathophysiology of amatoxin poisoning, we discuss a potential therapeutic approach.
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http://dx.doi.org/10.1055/s-0042-103987DOI Listing
July 2016

Long-Term Renal Function in Liver Transplant Recipients After Conversion From Calcineurin Inhibitors to mTOR Inhibitors.

Ann Transplant 2015 Nov 26;20:707-13. Epub 2015 Nov 26.

Department of Transplant Medicine, University Hospital Münster, Münster, Germany.

Background: Renal dysfunction often occurs in liver transplant (LT) recipients receiving calcineurin inhibitor (CNI)-based immunosuppressive regimens, increasing morbidity and mortality rates. Replacement of CNIs by mTOR inhibitor-based immunosuppressive protocols may prevent renal impairment in LT recipients.

Material/methods: Outcomes in patients who underwent LT between 1996 and 2010 at our center and who were switched from CNI-based to mTOR inhibitor-based immunosuppression were retrospectively analyzed. Renal course, hyperlipidemia, and graft rejection were assessed in patients maintained on this CNI-free regimen for at least 24 months.

Results: Of the 85 patients switched from CNI-based to mTOR inhibitor-based, CNI-free immunosuppression, 78 met the inclusion criteria. Within the first 6 weeks after switching, the covariable adjusted estimated glomerular filtration rate (eGFR) increased 5.6 mL/min [95% confidence interval 2.6-8.7 mL/min, p<0.001], but there were no further statistically noticeable changes in eGFR. Concentrations of cholesterol and triglycerides increased statistically, noticeable within the first 12 months after drug conversion. Histologically proven graft rejection was observed in 4 patients (5.1%) after conversion.

Conclusions: Conversion from CNI-based to CNI-free, mTOR inhibitor-based immunosuppression after LT is safe and can result in significant renal recovery. CNI-free, mTOR inhibitor-based immunosuppression is a potential option for patients with contraindications for CNIs and for LT recipients with rapid reduction in kidney function due to CNIs.
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http://dx.doi.org/10.12659/aot.895320DOI Listing
November 2015

Interferon-Free Sofosbuvir-Based Anti-HCV Therapy After Liver Transplantation.

Ann Transplant 2015 Sep 22;20:561-8. Epub 2015 Sep 22.

Department of Transplantation Medicine, University Hospital Münster, Münster, Germany.

Background: Therapy for HCV-infected patients after orthotopic liver transplantation (OLT) is based on interferon (IFN) as the gold standard, but sustained virologic response (SVR) and safety profiles of the IFN-based therapies are very unsatisfactory. The aim of this continuing analysis is evaluation of the impact of an IFN-free sofosbuvir (SOF)-based therapy in HCV-infected liver transplant recipients.

Material And Methods: Post-OLT patients with a proven recurrence of HCV were treated with SOF and ribavirin (RBV) for 24 weeks (n=10). Laboratory parameters and FibroScan® are continuously evaluated at weeks 0, 12, 24, and 36. A retrospectively analyzed HCV patient cohort who received antiviral therapy with pegylated INF and RBV± telaprevir (TLV) were used as a control group.

Results: All patients who finished their treatment with SOF/RBV at least 12 weeks ago showed an SVR. The SOF-based therapy showed a significantly higher rate of rapid virologic response (RVR) and sustained virologic response (SVR) compared to the IFN-based therapies (RVR: p=0.007; SVR: p=0.009). According to temporary data on FibroScan® analysis, regression of fibrosis was observed in 8 patients treated with SOF/RBV. No premature termination of SOF became necessary.

Conclusions: In this small group of patients, the preliminary results indicate that a regression of fibrosis is achievable within 24 weeks of therapy with SOF after OLT. SOF seems to be effective and safe in the treatment of OLT patients infected with HCV and will likely improve patient and transplant survival.
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http://dx.doi.org/10.12659/AOT.893640DOI Listing
September 2015

Hepatitis C in Special Patient Cohorts: New Opportunities in Decompensated Liver Cirrhosis, End-Stage Renal Disease and Transplant Medicine.

Int J Mol Sci 2015 Aug 5;16(8):18033-53. Epub 2015 Aug 5.

Department of Transplant Medicine, University Hospital Muenster, 48149 Münster, Germany.

Worldwide, hepatitis C virus (HCV) is a common infection. Due to new antiviral approaches and the approval of direct-acting antiviral agents (DAA), HCV therapy has become more comfortable. Nevertheless, there are special patient groups, in whom treatment of HCV is still challenging. Due to only few data available, tolerability and efficacy of DAAs in special patient cohorts still remain unclear. Such special patient cohorts comprise HCV in patients with decompensated liver disease (Child-Pugh Class B or C), patients with chronic kidney disease, and patients on waiting lists to renal/liver transplantation or those with HCV recurrence after liver transplantation. HCV infection in these patient cohorts has been shown to be associated with increased morbidity and mortality and may lead to reduced graft survival after transplantation. Successful eradication of HCV results in a better outcome concerning liver-related complications and in a better clinical outcome of these patients. In this review, we analyze available data and results from recently published literature and provide an overview of current recommendations of HCV-therapy regimen in these special patient cohorts.
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http://dx.doi.org/10.3390/ijms160818033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4581234PMC
August 2015

Comparative analysis of ERCP, IDUS, EUS and CT in predicting malignant bile duct strictures.

World J Gastroenterol 2014 Aug;20(30):10495-503

Hauke S Heinzow, Carina Rammes, Dirk Domagk, Department of Medicine B, University of Münster, D-48149 Münster, Germany.

Aim: To compare endoscopic retrograde cholangio-pancreatography (ERCP), intraductal ultrasound (IDUS), endosonography (EUS), endoscopic transpapillary forceps biopsies (ETP) and computed tomography (CT) with respect to diagnosing malignant bile duct strictures.

Methods: A patient cohort with bile duct strictures of unknown etiology was examined by ERCP and IDUS, ETP, EUS, and CT. The sensitivity, specificity, and accuracy rates of the diagnostic procedures were calculated based on the definite diagnoses proved by histopathology or long-term follow-up in those patients who did not undergo surgery. For each of the diagnostic measures, the sensitivity, specificity, and accuracy rates were calculated. In all cases, the gold standard was the histopathologic staging of specimens or long-term follow-up of at least 12 mo. A comparison of the accuracy rates between the localization of strictures was performed by using the Mann-Whitney U-test and the χ(2) test as appropriate. A comparison of the accuracy rates between the diagnostic procedures was performed by using the McNemar's test. Differences were considered statistically significant if P < 0.05.

Results: A total of 234 patients (127 males, 107 females, median age 64, range 20-90 years) with indeterminate bile duct strictures were included. A total of 161 patients underwent operative exploration; thus, a surgical histopathological correlation was available for those patients. A total of 113 patients had malignant disease proven by surgery; in 48 patients, benign disease was surgically found. In these patients, the decision for surgical exploration was made due to the suspicion of malignant disease in multimodal diagnostics (ERCP, CT, or EUS). Fifty patients had a benign diagnosis and were followed by a surveillance protocol with a follow-up of at least 12 mo; the median follow-up was 34 mo. Twenty-three patients had extended malignant disease, and thus were considered palliative. A comparison of the different diagnostic tools for detecting bile duct malignancy resulted in accuracy rates of 91% (ERCP/IDUS), 59% (ETP), 92% (IDUS + ETP), 74% (EUS), and 73% (CT), respectively. In the subgroup analysis, the accuracy rates (%, ERCP + IDUS/ETP/IDUS + ETP; EUS; CT) for each tumor entity were as follows: cholangiocellular carcinoma: 92%/74%/92%/70%/79%; pancreatic carcinoma: 90%/68%/90%/81%/76%; and ampullary carcinoma: 88%/90%/90%/76%/76%. The detection rate of malignancy by ERCP/IDUS was superior to ETP (91% vs 59%, P < 0.0001), EUS (91% vs 74%, P < 0.0001) and CT (91% vs 73%, P < 0.0001); EUS was comparable to CT (74% vs 73%, P = 0.649). When analyzing accuracy rates with regard to localization of the bile duct stenosis, the accuracy rate of EUS for proximal vs distal stenosis was significantly higher for distal stenosis (79% vs 57%, P < 0.0001).

Conclusion: ERCP/IDUS is superior to EUS and CT in providing accurate diagnoses of bile duct strictures of uncertain etiology. Multimodal diagnostics is recommended.
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http://dx.doi.org/10.3748/wjg.v20.i30.10495DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4130858PMC
August 2014

Endocuff-assisted colonoscopy: a new accessory to improve adenoma detection rate? Technical aspects and first clinical experiences.

Endoscopy 2014 Jul 13;46(7):610-4. Epub 2014 May 13.

Department of Medicine B, University of Muenster, Muenster, Germany.

Background And Study Aims: The Endocuff is a new colonoscopy accessory that has been designed to improve both the adenoma detection rate and endoscope tip control.

Patients And Methods: A total of 50 Endocuff-assisted colonoscopies were analyzed retrospectively with regard to safety, procedural success, and complications.

Results: The cecal intubation rate was 98 %, and the mean intubation time was 6.0 minutes (95 % confidence interval 5.3 - 6.6 minutes). The ileal intubation rate was 76 %. In 30 % of patients, the Endocuff caused small, superficial, "scratch-like" mucosal lesions. In all other patients, no Endocuff-associated complications were observed. A total of 36 adenomas were detected in 50 patients. The adenoma detection rate was 34 %.

Conclusions: Endocuff-assisted colonoscopy showed good procedural success rates in terms of cecal intubation rate and time, and a promising adenoma detection rate. Endocuff seems to improve endoscope tip control, especially during polypectomy. Endocuff may be a useful device for colorectal adenoma screening, and should be investigated in larger trials.
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http://dx.doi.org/10.1055/s-0034-1365446DOI Listing
July 2014