Publications by authors named "Steffen Kunsch"

32 Publications

Evaluation of ustekinumab trough levels during induction and maintenance therapy with regard to disease activity status in difficult to treat Crohn disease patients.

Medicine (Baltimore) 2021 Mar;100(11):e25111

Clinic for Gastroenterology, Gastrointestinal Oncology and Endocrinology.

Abstract: Ustekinumab (UST) is approved for the treatment of moderate and severe Crohn disease (CD). Therapeutic drug monitoring (TDM) can help monitor the therapeutic effects of biologics. Therefore, the aim of this study was to evaluate the clinical outcomes of UST-treated CD patients and to determine the UST trough level in clinical and corticosteroid-free remission.This retrospective study included patients with moderate and severe active disease (AD) treated intravenously with a weight-adapted induction dose of UST. The maintenance therapy consisted of 90 mg UST subcutaneously at week 8 and thereafter every 8 or 12 weeks, depending on the clinical response. Clinical and corticosteroid-free remission, Harvey-Bradshaw-Index (HBI), UST trough level, and further laboratory parameters were measured just before the injection of UST at each follow-up evaluation until week 40.37 CD patients with a median HBI of 9 at week 0 were included in the study. Starting from 24% at the beginning of the monitoring period, and 38% of patients at the end of the monitoring period were treated with an 8-week interval (P = .18). There was a significant improvement in clinical (P = .0004), corticosteroid-free remission (P = .03), and HBI (P < .0001) from week 0 until the end of the observation period. The serum UST trough level decreased significantly from 2.0 at week 8 to 0.3, in the maintenance therapy and 0.4 μg/ml at the end of the therapy (P < .0001). Neither UST trough level nor levels of C-reactive protein (CRP) or fecal calprotectin (FC) were associated with disease outcome. Concomitant immunomodulator therapy did not appear to affect the UST trough level or clinical course.UST is an effective treatment option for difficult-to-treat patients with CD. UST trough levels may not be associated with treatment efficacy or the prediction of treatment outcomes in patients with CD. Further prospective randomized trials should be conducted to evaluate whether UST trough levels are associated with treatment outcomes in patients with CD.
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http://dx.doi.org/10.1097/MD.0000000000025111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7982165PMC
March 2021

Endoscopic internal drainage and low negative-pressure endoscopic vacuum therapy for anastomotic leaks after oncologic upper gastrointestinal surgery.

Endoscopy 2021 Jan 27. Epub 2021 Jan 27.

Department of Gastroenterology and Gastrointestinal Oncology, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris and University of Paris, Paris, France.

Background:  Endoscopic internal drainage (EID) with double-pigtail stents or low negative-pressure endoscopic vacuum therapy (EVT) are treatment options for leakage after upper gastrointestinal oncologic surgery. We aimed to compare the effectiveness of these techniques.

Methods:  Between 2016 and 2019, patients treated with EID in five centers in France and with EVT in Göttingen, Germany were included and retrospectively analyzed using univariate analysis. Pigtail stents were changed every 4 weeks; EVT was repeated every 3-4 days until leak closure.

Results:  35 EID and 27 EVT patients were included, with a median (interquartile range [IQR]) leak size of 0.75 cm (0.5-1.5). Overall treatment success was 100 % (95 % confidence interval [CI] 90 %-100 %) for EID vs. 85.2 % (95 %CI 66.3 %-95.8 %) for EVT ( = 0.03). The median (IQR) number of endoscopic procedures was 2 (2-3) vs. 3 (2-6.5;  = 0.003) and the median (IQR) treatment duration was 42 days (28-60) vs. 17 days (7.5-28;  < 0.001), for EID vs. EVT, respectively.

Conclusion:  EID and EVT provide high closure rates for upper gastrointestinal anastomotic leaks. EVT provides a shorter treatment duration, at the cost of a higher number of procedures.
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http://dx.doi.org/10.1055/a-1375-8151DOI 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

Comparison of Chest Ultrasound and Standard X-Ray Imaging in COVID-19 Patients.

Ultrasound Int Open 2020 Sep 2;6(2):E36-E40. Epub 2020 Sep 2.

Department of Gastroenterology, Gastrointestinal Oncology and Endocrinology, University Medical Center Göttingen, Gottingen, Germany.

Purpose: The COVID-19 pandemic poses new challenges for the medical community due to its large number of patients presenting with varying symptoms. Chest ultrasound (ChUS) may be particularly useful in the early clinical management in suspected COVID-19 patients due to its broad availability and rapid application. We aimed to investigate patterns of ChUS in COVID-19 patients and compare the findings with results from chest X-ray (CRX).

Materials And Methods: 24 patients (18 symptomatic, 6 asymptomatic) with confirmed SARS-CoV-2 by polymerase chain reaction underwent bedside ChUS in addition to CRX following admission. Subsequently, the results of ChUS and CRX were compared.

Results: 94% (n=17/18) of patients with respiratory symptoms demonstrated lung abnormalities on ChUS. ChUS was especially useful to detect interstitial syndrome compared to CXR in COVID-19 patients (17/18 vs. 11/18; p<0.02). Of note, ChUS also detected lung consolidations very effectively (14/18 for ChUS vs. 7/18 cases for CXR; p<0.02). Besides pathological B-lines and subpleural consolidations, pleural line abnormality (89%; n=16/18) was the third most common feature in patients with respiratory manifestations of COVID-19 detected by ChUS.

Conclusion: Our findings support the high value of ChUS in the management of COVID-19 patients.
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http://dx.doi.org/10.1055/a-1217-1603DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7467801PMC
September 2020

Endoscopic submucosal dissection with an additional working channel (ESD+): a novel technique to improve procedure time and safety of ESD.

Surg Endosc 2020 Jul 16. Epub 2020 Jul 16.

Department of Gastroenterology and Gastrointestinal Oncology, University Medical Center Goettingen, Georg-August-University, 37075, Göttingen, Germany.

Background And Aims: A new external additional working channel (AWC) was recently introduced by which endoscopic submucosal dissection (ESD) can be converted to a technique termed "ESD+ ". We aim to systematically evaluate this novel technique in flat gastric lesions and compare it to classical ESD.

Methods: The study was prospectively conducted in a pre-clinical ex vivo animal model (EASIE-R simulator) with porcine stomachs. Prior to intervention, we set standardized lesions measuring 3 cm or 4 cm in antegrade as well as in retrograde positions.

Results: Overall, 64 procedures were performed by an experienced endoscopist. Both techniques were reliable and showed en bloc resection rates of 100%. Overall, ESD+ reduced time of procedure compared to ESD (24.5 vs. 32.5 min, p = 0.025*). Particularly, ESD+ was significantly faster in retrograde lesions with a median of 22.5 vs. 34.0 min in 3 cm retrograde lesions (p = 0.002*) and 34.5 vs. 41.0 min (p = 0.011*) in 4 cm retrograde lesions. There were 0 perforations with both techniques. In ESD+ , 1 muscularis damage occurred (3.13%) compared to 6 muscularis damages with ESD (18.75%, p = 0.045*).

Conclusions: By its grasp-and-mobilize technique, ESD+ allows potentially faster and safer resections of flat gastric lesions compared to conventional ESD in an ex vivo porcine model. The potential advantages of ESD+ in terms of procedure time may be particularly relevant for difficult lesions in retrograde positions.
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http://dx.doi.org/10.1007/s00464-020-07808-wDOI Listing
July 2020

Association of serum interleukin-6 and soluble interleukin-2-receptor levels with disease activity status in patients with inflammatory bowel disease: A prospective observational study.

PLoS One 2020 29;15(5):e0233811. Epub 2020 May 29.

Department of Gastroenterology and Gastrointestinal Oncology, University Medical Center Goettingen, Goettingen, Germany.

Crohn's disease (CD) and ulcerative colitis (UC) are characterized by overexpression of proinflammatory cytokines. We determined the association of serum levels of interleukin (IL)-6, soluble-IL-2-receptor (sIL-2R) and CRP as well as of faecal calprotectin (FC) values with disease activity in CD and UC patients. This prospective study included 145 CD and 84 UC patients. Serum proinflammatory biomarkers and FC levels were measured and demographic, clinical and endoscopic characteristics were collected. Uni- and multivariate statistical analyses were performed. Serum IL-6 and CRP levels as well as FC values of CD patients were associated with clinical and endoscopic remission. In multivariate analysis serum IL-6 levels remained significantly associated with clinical and endoscopic remission. FC levels were also associated with endoscopic remission in CD patients. CD patients under the threshold levels of 8.5 pg/mL and 5.5 pg/mL for serum IL-6 were in 70% and 66% in clinical and endoscopic remission, respectively. Serum sIL-2R, CRP levels and FC values of UC patients were associated in univariate analysis with clinical and endoscopic remission. In multivariate analysis CRP and FC values were associated with clinical remission and serum sIL-2R as well as FC levels with endoscopic remission. UC patients under the threshold levels of 759 IU/mL and 646 IU/mL for serum sIL-2R were in 76% and 76% in clinical and endoscopic remission, respectively. Beside CRP and FC, serum IL-6 levels in CD patients and sIL-2R levels in UC patients can be a further useful non-invasive biomarker to identify the disease activity status.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0233811PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7259981PMC
August 2020

Diagnostic accuracy of B-Mode ultrasound and Hepatorenal Index for graduation of hepatic steatosis in patients with chronic liver disease.

PLoS One 2020 1;15(5):e0231044. Epub 2020 May 1.

Department of Gastroenterology and Gastrointestinal Oncology, University Medical Center Goettingen, Goettingen, Germany.

Background/aims: The aim of our study was to evaluate the diagnostic accuracy of B-Mode ultrasound and Hepatorenal Index (HRI) by high-end devices for the detection and classification of hepatic steatosis in patients with various causes of chronic liver disease (CLD).

Methods: We retrospectively enrolled patients with CLD who underwent liver biopsy and baseline ultrasound between March 2016 and May 2019. Sonographic graduation of steatosis (0°-III°) using B-Mode criteria and HRI were correlated with the histological graduation (S0 (<5% fat), S1 (≥5-33%), S2 (>33-66%) and S3 (>66%). Interobserver agreement was calculated.

Results: 157 patients were evaluated. B-Mode ultrasound had a sensitivity of 75.6% and a specificity of 76.0% to differentiate between steatosis and no steatosis (AUROC 0.758). Using B-Mode criteria for advanced steatosis (≥II°), specificity for presence of histological steatosis was ≥98.7%. For detection of advanced steatosis (≥S2), sensitivity of B-mode criteria was 90.9%. In a subgroup of patients with advanced liver fibrosis, sensitivity of B-mode criteria was 95.0% for detection of advanced steatosis (S≥2). A HRI cut-off-value of 1.46 differentiates between patients with steatosis and patients without steatosis with a sensitivity of 42.7% and a specificity of 90.7% (AUROC 0.680). Interobserver agreement of both B-Mode and HRI was good to excellent.

Conclusion: B-Mode ultrasound using high-end devices is an excellent method to detect advanced steatosis in patients with various CLD. For diagnosis of mild steatosis, modern ultrasound devices may have higher sensitivity but at the expense of specificity. Stage of fibrosis and etiology of CLD seem not to impact on diagnostic accuracy. The additional calculation of HRI seems to have no additional benefit with regard to detect or grade hepatic steatosis in our study population.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0231044PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7194436PMC
July 2020

Impact of Endoscopic Vacuum Therapy with Low Negative Pressure for Esophageal Perforations and Postoperative Anastomotic Esophageal Leaks.

Digestion 2020 Feb 11:1-11. Epub 2020 Feb 11.

Department of Gastroenterology and Gastrointestinal Oncology, University Medical Center Göttingen, Göttingen, Germany,

Introduction: Management of esophageal anastomotic leaks (AL) and esophageal perforations (EP) remains difficult and often requires an interdisciplinary treatment modality. For primary endoscopic management, self-expanding metallic stent (SEMS) placement is often considered first-line therapy. Recently, endoscopic vacuum therapy (EVT) has emerged as an alternative or adjunct for management of these conditions. So far, data for EVT in the upper gastrointestinal-tract is restricted to single centre, non-randomized trials. No studies on optimal negative pressure application during EVT exist. The aim of our study is to describe our centre's experience with low negative pressure (LNP) EVT for these indications over the past 5-years.

Patients And Methods: Between January 2014 and December 2018, 30 patients were endoscopically treated for AL (n = 23) or EP (n = 7). All patients were primarily treated with EVT and LNP between -20 and -50 mm Hg. Additional endoscopic treatment was added when EVT failed. Procedural and peri-procedural data, as well as clinical outcomes including morbidity and mortality, were analysed.

Results: Clinical successful endoscopic treatment of EP and AL was achieved in 83.3% (n = 25/30), with 73.3% success using EVT alone (n = 22/30). Mean treatment duration until leak closure was 16.1 days (range 2-58 days). Additional treatment modalities for complete leak resolution was necessary in 10% (n = 3/30), including SEMS placement and fibrin glue injection. Mean hospital stay for patients with EP was shorter with 33.7 days compared to AL with 54.4 days (p = 0.08). Estimated preoperative 10-year overall survival (Charlson comorbidity score) was 39.4% in patients with AL and 59.9% in patients with EP (p = 0.26). A mean of 5.1 EVT changes (range 1-12) was needed in EP and 3.6 changes (range 1-13) in AL to achieve complete closure, switch to other treatment modality, or reach endoscopic failure (p = 0.38).

Conclusion: LNP EVT enables effective minimally - invasive endoluminal leak closure from anastomotic esophageal leaks and EP in high-morbid patients. In this study, EVT was combined with other endoscopic treatment options such as SEMS placement or fibrin glue injection in order to achieve leak or perforation closure in the vast majority of patients (83.3%). Low aspiration pressures led to slower but still sufficient clinical results.
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http://dx.doi.org/10.1159/000506101DOI Listing
February 2020

Endoscopic mucosal resection with an additional working channel (EMR+) in a porcine ex vivo model: a novel technique to improve en bloc resection rate of snare polypectomy.

Endosc Int Open 2020 Feb 22;8(2):E99-E104. Epub 2020 Jan 22.

Department of Gastroenterology and Gastrointestinal Oncology, University Medical Center, Goettingen, Germany.

 Recently, a new external additional working channel (AWC) was introduced by which conventional endoscopic mucosal resection (EMR) can be improved to a technique termed "EMR+". We first evaluated this novel technique in comparison to classical EMR in flat lesions.  The trial was prospectively conducted in an ex vivo animal model with porcine stomachs placed into the EASIE-R simulator. Prior to intervention, standardized lesions were set by coagulation dots, measuring 1, 2, 3 or 4 cm.  Overall, 152 procedures were performed. EMR and EMR+ were both very reliable in 1-cm lesions, each showing en bloc resection rates of 100 %. EMR+ en bloc resection rate was significantly higher in 2-cm lesions (95.44 % vs. 54.55 %,  = 0.02), in 3-cm lesions (86.36 % vs. 18.18 %,  < 0.01) and also in 4-cm lesions (60.00 % vs. 0 %,  < 0.01). Perforations occurred only in EMR+ procedures in 4-cm lesions (3 of 20; 15 %).  With its grasp-and-snare technique, EMR+ facilitates en bloc resection of larger lesions compared to conventional EMR. In lesions 2 cm and larger, EMR+ has demonstrated advantages, especially concerning en bloc resection rate. At 3 cm, EMR+ reaches its best discriminatory power whereas EMR+ has inherent limits at 4 cm and in lesions of that size, other techniques such as ESD or surgery should be considered.
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http://dx.doi.org/10.1055/a-0996-8050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6976338PMC
February 2020

Noninvasive assessment of liver fibrosis in a real-world cohort of patients with known or suspected chronic liver disease using 2D-shear wave elastography.

Eur J Gastroenterol Hepatol 2020 12;32(12):1559-1565

Department of Gastroenterology and Gastrointestinal Oncology.

Objectives: We aimed to investigate the diagnostic accuracy of liver stiffness measurement (LSM) by 2D-shear wave elastography (2D-SWE, GE, Logiq E9) in patients with known or suspected chronic liver disease and to define cutoff values for the different stages of fibrosis.

Methods: First, we retrospectively enrolled 21 patients in a pilot study and validated the results in a prospective cohort of 70 patients between May 2017 and February 2019. In all patients, LSM and liver biopsy were performed. We analyzed the diagnostic accuracy of LSM for the different fibrosis stages and examined the impact of additional clinical parameters on LSM.

Results: The success rate of LSM was 88.6%. In the prospective cohort, optimal cutoff values for F ≥ 1, F ≥ 2, F ≥ 3 and F = 4 were 6.24, 7.86, 8.05 and 10.74 kPa [area under the receiver operating characteristic curve (AUROC) 0.831, 0.913, 0.996 and 0.954]. In both cohorts and in the subgroup of patients with nonalcoholic fatty liver disease (NAFLD) (n = 35), a cutoff value of 8.05 kPa differentiates patients with advanced fibrosis (F ≥ 3) and patients with no or mild fibrosis (F0-F2) with high diagnostic accuracy (AUROC 0.995-1.000). Parameters such as age, sex, BMI, bilirubin- and alanine aminotransferase-level had no significant impact on LSM.

Conclusion: LSM by 2D-SWE is an excellent method to differentiate between patients with advanced fibrosis (F ≥ 3) and patients with no or mild fibrosis (F ≤ 2). We were able to show this also in a subgroup of patients with NAFLD.
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http://dx.doi.org/10.1097/MEG.0000000000001675DOI Listing
December 2020

[Quality improvement in conservative pain management (QUIKS) : A module of the QUIPS project for benchmarking of pain treatment in patients with nonoperative care].

Schmerz 2020 Feb;34(1):52-64

Klinik für Anästhesie und Intensivmedizin, Universitätsklinikum Jena, Jena, Deutschland.

Background: National and international surveys have shown that the quality of pain therapy in hospitals shows deficits, especially in the nonoperative disciplines.

Objective: The objective was to develop and clinically validate a module for the outcome and process parameters for pain management in patients in the context of a conservative/nonoperative hospital treatment analogous to the QUIPS questionnaire (quality improvement in postoperative pain therapy), which focuses on postoperative pain management.

Material And Methods: In a 4-step procedure the QUIPS outcome questionnaire and the process assessment sheet of the QUIPS module were adapted to the conditions of conservative/nonoperative treatment. Patients from internal medicine, neurology and dermatology took part in the systematic testing and the clinical validation.

Results: A total of 973 patients were enrolled (inclusion rate 74%, n = 403 internal medicine, n = 401 neurology, n = 169 dermatology). The majority completed the questionnaire independently while 33% of the patients needed support, which was given in the form of an interview. Apart from a few deficits, most questions about pain intensity and function were fully recorded. The evaluation of the outcome was difficult as regardless of the pain therapy, a relevant proportion of the patients reported no pain. Due to the lack of conclusive diagnoses at the time of the assessment, organ-related disease groups were developed using word diagnoses instead of the OPS coding used in QUIPS.

Conclusion: In addition to the perioperative modules of QUIPS, QUIKS (quality improvement in conservative pain management), an instrument for quality assurance of pain treatment in patients in nonoperative disciplines, is now available.
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http://dx.doi.org/10.1007/s00482-019-00429-wDOI Listing
February 2020

Impact of faecal calprotectin measurement on clinical decision-making in patients with Crohn's disease and ulcerative colitis.

PLoS One 2019 24;14(10):e0223893. Epub 2019 Oct 24.

Department of Gastroenterology and Gastrointestinal Oncology, University Medical Center Goettingen, Goettingen, Lower Saxony, Germany.

Background: Faecal calprotectin (FC) seems to be the best available biomarker for the detection of intestinal inflammation in patients with inflammatory bowel disease (IBD). The aim of this study is to clarify whether the measurement of FC has changed the number of ultrasound and endoscopic procedures, drug modifications, as well as FC re-measurements in IBD patients.

Methods: This retrospective study included 242 IBD patients with available FC values (case cohort) and 46 patients without an available FC value (control cohort). Clinical consequences such as carrying out abdominal ultrasound, endoscopy, drug modification or FC re-measurement at the next ambulatory presentation or during in-patient stay were collected. Statistical analysis was performed to determine the association between clinical decision-making and patient's characteristics, especially FC value.

Results: Overall, 192 (67%) clinical consequences were noted in both cohorts. In the case cohort 174 (91%) implications were noted compared to 18 (9%) in the control cohort (P < 0.001). In the case cohort, significantly more clinical consequences were detected in patients with Crohn's disease (CD) as well as in ulcerative colitis (UC) patients with a FC value > 250 mg/Kg than in patients with a value of ≤ 250 mg/Kg. In CD patients with high FC values significantly increased numbers of abdominal ultrasounds, endoscopies and FC re-measurements were noted. In UC patients with high FC values significantly increased numbers of abdominal ultrasounds, drug modifications and FC re-measurements were noted.

Conclusion: Measurement of FC may alter physician's clinical decision-making in IBD patients beside other clinical and diagnostic parameters. Further prospective and survey studies are warranted to evaluate the influence of FC measurement in the daily clinical decision-making.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0223893PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6812761PMC
March 2020

Distinct Association of Serum Vitamin D Concentration with Disease Activity and Trough Levels of Infliximab and Adalimumab during Inflammatory Bowel Disease Treatment.

Digestion 2020 19;101(6):761-770. Epub 2019 Sep 19.

Department of Gastroenterology and Gastrointestinal Oncology, University Medical Centre Göttingen, Göttingen, Germany,

Background: Studies of serum vitamin D (Vit-D) levels in patients with inflammatory bowel disease (IBD) treated with anti-tumor necrosis factor-alpha (anti-TNF-α) agents are scarce. The conjunction of Vit-D as well as zinc levels and anti-TNF-α-trough concentrations (TC) has not yet been explored.

Objectives: To determine the association of serum Vit-D, zinc and C-reactive protein (CRP) levels with clinical and biochemical remission and a possible correlation with serum TC and antibody levels of anti-TNF-α.

Methods: Serum Vit-D and zinc levels as well as Infliximab (IFX) and Adalimumab (ADA) TC during the maintenance phase of treatment were measured in 112 IBD patients. Statistical analysis were performed for clinical and biochemical remission.

Results: Vit-D and zinc deficiency were detected in 58 and 4.5% of the patients respectively. In IFX-treated patients, IFX-TC, Vit-D and CRP levels were associated independently with clinical remission with an OR of 20 (95% CI 1.3-333, p = 0.03), 1.3 (95% CI 1.1-1.7, p = 0.02) and 0.4 (95% CI 0.2-0.8, p = 0.01) respectively. Serum IFX-TC and Vit-D levels correlated positively (r = 0.39, p = 0.001), while serum IFX-TC and CRP levels showed an inverse correlation (r = -0.43, p < 0.001). Only -IFX-TC associated independently with biochemical remission with a threshold of 3.1 µg/mL. In ADA-treated patients, ADA-TC associated independently with clinical and biochemical remission with an OR of 2.5 (95% CI 1.1-5.0, p = 0.04) and 1.3 (95% CI 1.1-1.4, p = 0.03) respectively. The serum zinc level was associated neither with clinical nor with biochemical remission in either cohort.

Conclusions: Our results indicate that serum Vit-D level may be a predictive marker in addition to drug trough levels in IBD patients treated with IFX. Furthermore, due to the correlation between serum IFX and Vit-D levels, Vit-D substitution should be conducted in patients with low Vit-D levels.
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http://dx.doi.org/10.1159/000502515DOI Listing
September 2019

Prospective comparison of 2D-shearwave elastography in both liver lobes in healthy subjects and in patients with chronic liver disease.

Scand J Gastroenterol 2019 Sep 21;54(9):1138-1145. Epub 2019 Aug 21.

Department of Gastroenterology and Gastrointestinal Oncology, University Medical Center Goettingen , Goettingen , Germany.

2D-shearwave elastography is an established method for liver stiffness measurement (LSM). However, the success rate of LSM using the recommended standard technique in the right lobe is limited by several factors. We aimed to compare LSM in the right and left liver lobe in order to evaluate whether LSM in the left lobe could be an alternative if measurements in the right lobe are not feasible. A total of 116 subjects, 58 healthy volunteers and 58 patients with chronic liver disease (CLD), were prospectively included. LSM were performed in the right lobe and in the left lobe, both in neutral and in inspiration position. LSM in the left lobe (8.39(±4.83)kPa) was significantly ( < .001) higher than LSM in the right lobe (6.27(±2.45)kPa). LSM in inspiration position (8.60(±4.33) kPa) was significantly ( = .009) higher than LSM in neutral position (7.70(±3.01)kPa). LSM in the left lobe overestimated the grade of fibrosis in 50.0% of the patients with CLD. However, correlation between LSM values right and left was strong ( = 0.856) and additional use of LSM in the left lobe increased the success rate from 106/116 (91.4%) to 112/116 (96.6%;  = .098). High skin-to-liver-capsule-distance and presence of ascites were independent risk factors for non-successful LSM. Despite significantly higher values, LSM in the left lobe may be an alternative if LSM in the right lobe is not feasible, and cirrhosis can be ruled out with high probability if LSM is within the normal range.
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http://dx.doi.org/10.1080/00365521.2019.1653961DOI Listing
September 2019

Testing of Helicobacter pylori by Endoscopic Biopsy: The Clinical Dilemma of Suppressive Conditions.

Digestion 2020 19;101(5):552-556. Epub 2019 Jun 19.

Department of Gastroenterology and Gastrointestinal Oncology, University Medical Center Goettingen, Georg-August-University, Goettingen, Germany,

Background And Aims: Testing for Helicobacter pylori is frequently conducted during esophagogastroduodenoscopy (EGD). Suppressive conditions such as the intake of proton-pump inhibitors (PPIs), preceded antibiotic treatment or recent upper gastrointestinal bleeding impair H. pylori test quality. The aim of our study was to evaluate the frequency and pattern of H. pylori suppressive conditions in a large patient collective undergoing elective EGD in a German university hospital.

Methods: The trial was performed as a single-center study. Only elective EGD from inpatients and outpatients were included. Prior to endoscopy, H. pylori suppressive conditions were collected using a standardized questionnaire. If H. pylori testing was indicated according to the guidelines, always both histology and helicobacter urease test were performed in analogy to the Sydney classification.

Results: One thousand six hundred and thirty-one patients were included (median 61 years, 36.0% outpatients, 64.0% inpatients). Overall, 76.5% of patients were under H. pylori suppressive conditions. The main suppressive condition was the intake of PPIs (70.7%). In 819 (50.2%) of all included cases, H. pylori testing was performed. The following were the results: 17.3% (142) had a positive H. pylori testing and 82.7% (677) were negative. Of those with negative result, 70.0% were tested under suppressive conditions.

Conclusion: Guidelines recommend H. pylori testing under non-suppressive conditions. However, this does not always meet the clinical practice. Our data show that de facto, many patients undergoing elective EGD are tested for H. pylori under suppressive conditions coming along with a higher risk of potentially false negative results. Particularly, concerning this issue, further research is needed to improve and clarify everyday clinical practice.
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http://dx.doi.org/10.1159/000501270DOI Listing
June 2019

Serum vitamin D but not zinc levels are associated with different disease activity status in patients with inflammatory bowel disease.

Medicine (Baltimore) 2019 Apr;98(15):e15172

University Medical Center Göttingen, Department of Gastroenterology and Gastrointestinal Oncology, Robert- Koch-Str., Göttingen, Germany.

The incidence of inflammatory bowel disease (IBD) is increasing and the pathogenesis is still not completely understood. Micronutrients like vitamin D [25 (OH)D] and zinc play an important role in enzyme activities and the immune system. As the 25 (OH)D-receptor has been shown to be downregulated in patients with IBD, 25 (OH)D may emerge as a predictive marker for disease improvement. Studies on relationship of both micronutrients in IBD patients are lacking.We retrospectively evaluated serum levels of 25(OH)D and zinc together with baseline characteristics of 232 IBD patients. Uni- and multivariate analyses were performed for association between serum levels of 25(OH)D and zinc with clinical and deep remission (CR and DR).155 Crohn's disease (CD) and 77 ulcerative colitis (UC) patients were included. 54% (n = 125) and 6% (n = 14) of IBD patients showed deficient serum 25(OH)D levels below 20 ng/mL and zinc levels below 7 μmol/L. Serum 25(OH)D levels were significantly higher in IBD patients with CR (P = .02) and DR (P < .001) but not serum zinc levels, respectively. Serum 25(OH)D levels (P = .008), anti-tumor-necrosis-factor-α-trough-concentration (anti-TNF-α-TC) (P = .02) and CRP level (P = .02) were independently associated with CR in CD patients. Serum 25(OH)D threshold of 19 ng/mL discriminated CD patients with or without CR, having an area under the receiver operating curve analysis (AUROC) of 0.77 [95%-confidence interval (CI): 0.68-0.85]. In multivariate analysis serum 25(OH)D levels (P = .04) and anti-TNF-α-TC (P = .04) were associated with DR in CD patients. Serum 25(OH)D threshold of 26 ng/mL discriminated CD patients with or without DR, having an AUROC of 0.75 (95%-CI: 0.68-0.83).Serum 25(OH)D (P = .04) and fecal calprotectin levels (P = .04) were independently correlated with CR in UC patients. Serum 25(OH)D threshold of 32 ng/mL discriminated UC patients in CR with an AUROC of 0.83 (95%-CI: 0.71-0.95). Zinc levels did not correlate with disease activity status in CD or UC patients either.In conclusion, beside CRP and fecal calprotectin, serum 25(OH)D levels, but not serum zinc levels, may be an additional useful and noninvasive marker for characterizing different disease activity status of IBD patients. Measurement of serum 25(OH)D in IBD patients may be warranted. 25(OH)D supplementation in deficient IBD patients is recommended.
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http://dx.doi.org/10.1097/MD.0000000000015172DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6485817PMC
April 2019

Cytomegalovirus colitis in inflammatory bowel disease and after haematopoietic stem cell transplantation: diagnostic accuracy, predictors, risk factors and disease outcome.

BMJ Open Gastroenterol 2019 27;6(1):e000258. Epub 2019 Feb 27.

Department of Gastroenterology and Gastrointestinal Oncology, Universitatsklinikum Gottingen, Gottingen, Germany.

Background: Concurrent cytomegalovirus (CMV) colitis in inflammatory bowel disease (IBD) and after haematopoietic stem cell transplantation (HSCT) is an important clinical entity associated with high rates of morbidity and mortality.

Methods: A retrospective study of 47 patients with IBD and 61 HSCT patients was performed regarding the evaluation of diagnostic accuracy of applied methods, predictors, risk factors for CMV disease manifestation, the proportion of patients with antiviral treatment and disease outcome.

Results: The sensitivity of quantitative PCR (qPCR) with a cut-off value of >250 copies/mg for CMV colitis in patients with IBD and HSCT patients was 79% and 92%, respectively. Predictors for CMV colitis in the IBD cohort were anaemia and the presence of endoscopic ulcers. Glucocorticoids, calcineurin inhibitors and >2 concurrent lines of treatment with immunosuppressive drugs could be identified as risk factors for CMV colitis in the IBD cohort with an OR of 7.1 (95% CI 1.7 to 29.9), 21.3 (95% CI 2.4 to 188.7) and 13.4 (95% CI 3.2 to 56.1), respectively. Predictors and risk factors for CMV gastroenteritis in the HSCT cohort was the presence of endoscopic ulcers (OR 18.6, 95% CI 3.3 to 103.7) and >2 concurrent lines of treatment with immunosuppressive drugs. Antiviral therapy was administered in 70% of patients with IBD and 77% of HSCT patients with CMV disease. 71% of antiviral-treated patients with IBD showed an improvement of their disease activity and 14% underwent colectomy. The mortality rate of HSCT patients was 21% irrespective of their CMV status.

Conclusions: In addition to the implementation of histological methods, qPCR may be performed in patients with suspected high-risk IBD and HSCT patients for CMV colitis. Independent validations of these results in further prospective studies are needed.
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http://dx.doi.org/10.1136/bmjgast-2018-000258DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6398871PMC
February 2019

Evaluation of liver stiffness by 2D-SWE in combination with non-invasive parameters as predictors for esophageal varices in patients with advanced chronic liver disease.

Scand J Gastroenterol 2019 Mar 17;54(3):342-349. Epub 2019 Mar 17.

a Department of Gastroenterology and Gastrointestinal Oncology , University Medical Centre Goettingen , Goettingen , Germany.

Esophageal varices (EV) are common complications in patients with advanced chronic liver disease (ACLD). Non-invasive parameters to exclude EV in patients with ACLD would be desirable. The aim of this study was the evaluation of liver stiffness measurement (LSM) using 2D-shear wave elastography (GE Logiq E9) and other non-invasive parameters as predictors for EV. Hundred patients with ACLD were enrolled. Abdominal sonography, including measurement of gall bladder wall thickness (GBWT), spleen diameter and LSM, gastroscopy and blood test results were evaluated. Statistical analyses were performed for the association between EV and non-invasive parameters. Fifty-one per cent of the patients had EV. The mean LSM (14.6 kPa) and GBWT (3.88 mm) in the group with EV were significantly higher than in the group without EV (10.6 kPa; 2.94 mm;  < .01). Performing area under the receiver operating characteristic curve, LSM has a better diagnostic performance (0.781) than GBWT (0.707), spleen diameter (0.672) and platelet count (0.635). Combining LSM (cut-off 13.58 kPa) and GBWT (cut-off 3.07 mm) resulted in a sensitivity of 86.3% and a specificity of 71.4% for the presence of EV. A sensitivity of 100% (negative predictive value 1.0) was achieved at LSM >9 kPa or GBWT >4 mm. Following these criteria in our current study population, 18% of the gastroscopies could have been avoided. Combining LSM with non-invasive parameters, especially GBWT, improves the diagnostic accuracy for predicting EV. We suggest reconsidering screening gastroscopy in patients with ACLD who show LSM <9 kPa and GBWT <4 mm due to the very low risk of having varices.
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http://dx.doi.org/10.1080/00365521.2019.1585571DOI Listing
March 2019

Colonoscopy-assisted application of a 14/6t over-the-scope clip for treatment of a bleeding Dieulafoy lesion in the distal jejunum.

Endoscopy 2019 04 8;51(4):E92-E93. Epub 2019 Feb 8.

Department of Gastroenterology and Gastrointestinal Oncology, Center of Interdisciplinary Endoscopy, University Medical Center Göttingen, Germany.

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http://dx.doi.org/10.1055/a-0833-8079DOI Listing
April 2019

Use of an additional working channel for endoscopic mucosal resection (EMR +)of a pedunculated sessile serrated adenoma in the sigmoid colon.

Endoscopy 2019 03 11;51(3):279-280. Epub 2019 Jan 11.

Department of Gastroenterology and Gastrointestinal Oncology, Center of Interdisciplinary Endoscopy University Medical Centre Göttingen, Göttingen, Germany.

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http://dx.doi.org/10.1055/a-0809-4814DOI Listing
March 2019

Liver Stiffness Measured by 2-Dimensional Shear Wave Elastography: Prospective Evaluation of Healthy Volunteers and Patients With Liver Cirrhosis.

J Ultrasound Med 2019 Jul 11;38(7):1769-1777. Epub 2018 Dec 11.

Department Gastroenterology and Gastrointestinal Oncology, University Medical Center Goettingen, Goettingen, Germany.

Objectives: We aimed to establish normal values for liver stiffness measurement, performed by 2-dimensional shear wave elastography (LOGIQ E9; GE Healthcare, Wauwatosa, WI), in healthy volunteers, patients with nonhepatic morbidities, and patients with histologically confirmed liver cirrhosis.

Methods: A total of 175 participants were included between July 2016 and February 2018. Three cohorts were analyzed: healthy volunteers (n = 68), patients with healthy livers but nonhepatic morbidities (n = 57), and patients with liver cirrhosis (n = 50). Liver stiffness measurement was performed by 2 observers with different levels of experience to determine interobserver agreement.

Results: Of the 175 participants included, 91 were male, and the mean age ± SD was 44.4 ± 19.4 years. The success rate for 175 liver stiffness measurements was 95.4%. The number of unsuccessful measurements was significantly higher in the liver cirrhosis cohort (P = .04). The interobserver agreement was excellent (intraclass correlation coefficient, 0.87). Liver stiffness in the healthy-liver patient cohort (4.93 ± 0.83 kPa) was not significantly different from that in the healthy-volunteer cohort (5.19 ± 1.03 kPa; P = .13). Apart from male sex in the healthy-volunteer cohort, age, body mass index, mild steatosis, and nonhepatic morbidities had no significant impact on liver stiffness. Liver stiffness values in participants without liver disease (healthy volunteers and healthy-liver patients; n = 125) ranged from 3.62 to 7.02 kPa (2.5th-97.5th percentiles). Notably, there was no overlap of liver stiffness measurements between the patients without liver disease and the cirrhosis cohort (13.29 ± 3.27 kPa [7.76-19.49 kPa]).

Conclusions: Liver stiffness values in healthy individuals vary widely and are not dependent on age, body mass index, or specific nonhepatic comorbidities. Liver stiffness values within the normal range can noninvasively rule out cirrhosis, as liver stiffness is significantly higher in cirrhotic patients (P < .001). Two-dimensional shear wave elastography has excellent interobserver agreement.
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http://dx.doi.org/10.1002/jum.14866DOI Listing
July 2019

High Prevalence of Pathological Hydrogen Breath Tests in Patients with Functional Dyspepsia.

Digestion 2019 14;100(3):186-191. Epub 2018 Nov 14.

Department of Gastroenterology and Gastrointestinal Oncology, University Medical Center Goettingen, Goettingen, Germany.

Background/aims: The aim of the study is to investigate the frequency of pathological hydrogen breath tests (HBT) in patients with clinical features of functional dyspepsia (FD) meeting the Rome criteria and normal testing of upper endoscopy and abdominal sonography.

Methods: We retrospectively included patients who underwent HBT (lactose, fructose, or glucose) between 2006 and 2012 and who had symptoms of FD. Patients were divided into 2 groups according to medical history and diagnostic results: (I) patients with suspected FD according to the Rome III criteria and (II) patients with an alternative diagnosis such as gastroesophageal reflux disease (GERD) or Crohn's disease (CD).

Results: A total of 207/404 patients were assigned to the FD group and 44.4% of these had at least 1 positive HBT and thus more frequently than patients with GERD (20.7%; n = 111; p < 0.001) and with CD (31.7%; n = 63; p = 0.07). Lactose and fructose HBT, but not glucose HBT, occurred significantly more frequently with pathological results than in patients with GERD (p = 0.02; p = 0.002). The probability of a positive HBT increased significantly with increasing number of performed HBT (p < 0.001).

Conclusion: We suggest that HBT should be considered in the clinical management of patients with suspected FD. In cases of positive HBTs, a potential causal therapy can be initiated.
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http://dx.doi.org/10.1159/000494718DOI Listing
February 2020

Impact of Food Intake on Liver Stiffness Determined by 2-D Shear Wave Elastography: Prospective Interventional Study in 100 Healthy Patients.

Ultrasound Med Biol 2019 02 2;45(2):402-410. Epub 2018 Nov 2.

Department Gastroenterology and Gastrointestinal Oncology, University Medical Center Goettingen, Goettingen, Germany. Electronic address:

The aim was to evaluate the influence of food intake on liver stiffness measurement (LSM), performed with 2-D shear wave elastography (Logiq E9, GE Medical Systems, Wauwatosa, WI, USA). One hundred healthy volunteers were prospectively enrolled. Mean age was 25.8 (19-55) y, and mean body mass index was 22.43 (17.3-30.8) kg/m². Patients fasted for at least 3 h and subsequently ingested a liquid meal of 800 kcal. Liver stiffness and portal vein velocity were measured before and after food intake. Food intake resulted in significantly higher LSM values compared with baseline LSM (5.74 ± 0.94 kPa vs. 4.80 ± 0.94 kPa, p < 0.001). On multiple linear regression analysis, body mass index was significantly positively correlated with the LSM increase after food intake (p = 0.01). No correlation between the increase in LSM and the increase in post-prandial portal vein velocity was observed (r = 0.09). In summary, food intake has a significant influence on LSM. There is an 11% risk of misclassifying non-fasting, healthy patients as having significant fibrosis.
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http://dx.doi.org/10.1016/j.ultrasmedbio.2018.09.021DOI Listing
February 2019

Gall bladder wall thickening as non-invasive screening parameter for esophageal varices - a comparative endoscopic - sonographic study.

BMC Gastroenterol 2018 Aug 2;18(1):123. Epub 2018 Aug 2.

Department Gastroenterology and Gastrointestinal Oncology, University Medical Centre Goettingen Georg-August-University, Robert-Koch-Str. 40, 37075, Goettingen, Germany.

Background: The mortality due to hemorrhage of esophageal varices (EV) is still high. The predominant cause for EV is liver cirrhosis, which has a high prevalence in Western Europe. Therefore, non-invasive screening markers for the presence of EV are of interest. Here, we aim to investigate whether non-inflammatory gall bladder wall thickening (GBWT) may serve as predictor for the presence of EV in comparison and combination with other non-invasive clinical and laboratory parameters.

Methods: One hundred ninety four patients were retrospectively enrolled in the study. Abdominal ultrasound, upper endoscopy and blood tests were evaluated. GBWT, spleen size and the presence of ascites were evaluated by ultrasound. Platelet count and Child-Pugh-score were also recorded. The study population was categorized in two groups: 122 patients without esophageal varices (non EV) compared to 72 patients with EV were analyzed by uni-and multivariate analysis.

Results: In the EV group 46% showed a non-inflammatory GBWT of ≥4 mm, compared to 12% in the non-EV group (p < 0.01). GBWT was significantly higher in EV patients compared to the non-EV group (mean: 4.4 mm vs. 2.8 mm, p < 0.0001), and multivariate analysis confirmed GBWT as independent predictor for EV (p < 0.04). The platelets/GBWT ratio (cut-off > 46.2) had a sensitivity and specificity of 78 and 86%, PPV 76% and NPV of 87%, and ROC analysis calculated the AUC of 0.864 (CI 0.809-0.919).

Conclusions: GBWT occurs significantly more often in patients with EV. However, because of the low sensitivity, combination with other non-invasive parameters such as platelet count is recommended.
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http://dx.doi.org/10.1186/s12876-018-0852-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6090930PMC
August 2018

Individual endoscopic management of anastomotic insufficiency after esophagectomy for esophageal squamous cell carcinoma and creation of a neostomach.

Endoscopy 2018 03 12;50(3):E69-E71. Epub 2018 Jan 12.

Department of Gastroenterology and Gastrointestinal Oncology, Center of Interdisciplinary Endoscopy, University Medical Center Göttingen, Göttingen, Germany.

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http://dx.doi.org/10.1055/s-0043-124180DOI Listing
March 2018

A case report of delayed intra-abdominal and intra-luminal haemorrhage after polypectomy.

Z Gastroenterol 2017 Oct 11;55(10):1009-1013. Epub 2017 Oct 11.

Department of Gastroenterology and Gastrointestinal Oncology, University Medical Center Goettingen, Georg August University, Goettingen, Germany.

We report the case of a 70-year-old man who presented with hematochezia, anaemia, and severe abdominal pain 6 days after polypectomy. Contrast-enhanced ultrasound and computed tomography revealed no signs of free intra-abdominal air but showed intra-abdominal and intra-luminal bleeding. The patient was referred to colonoscopy in the operation room, which showed a coagula and venous bleeding at the polypectomy site. Emergency laparotomy was performed and revealed a large intra-abdominal mesocolic hematoma, which was surgically removed. The patient's post-operative recovery was uneventful. While few reports of splenic vessel rupture after colonoscopy due to traction on the splenocolic ligament have been published, delayed mesocolic hematoma without evidence of organ damage has not been reported so far. Clinicians need to be aware of these rare but life-threatening complications following colonoscopy.
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http://dx.doi.org/10.1055/s-0043-108125DOI Listing
October 2017

Higher adenoma detection rates with endocuff-assisted colonoscopy - a randomized controlled multicenter trial.

PLoS One 2014 3;9(12):e114267. Epub 2014 Dec 3.

Departments of Gastroenterology, HELIOS Albert-Schweitzer-Hospital Northeim, Northeim, Germany.

Objectives: The Endocuff is a device mounted on the tip of the colonoscope to help flatten the colonic folds during withdrawal. This study aimed to compare the adenoma detection rates between Endocuff-assisted (EC) colonoscopy and standard colonoscopy (SC).

Methods: This randomized prospective multicenter trial was conducted at four academic endoscopy units in Germany.

Participants: 500 patients (235 males, median age 64[IQR 54-73]) for colon adenoma detection purposes were included in the study. All patients were either allocated to EC or SC. The primary outcome measure was the determination of the adenoma detection rates (ADR).

Results: The ADR significantly increased with the use of the Endocuff compared to standard colonoscopy (35.4%[95% confidence interval{CI} 29-41%] vs. 20.7%[95%CI 15-26%], p<0.0001). Significantly more sessile polyps were detected by EC. Overall procedure time and withdrawal time did not differ. Caecal and ileum intubation rates were similar. No major adverse events occurred in both groups. In multivariate analysis, age (odds ratio [OR] 1.03; 95%[CI] 1.01-1.05), male sex (OR 1.74; 95%CI 1.10-2.73), withdrawal time (OR 1.16; 95%CI 1.05-1.30), procedure time (OR 1.07; 95%CI 1.04-1.10), colon cleanliness (OR 0.60; 95%CI 0.39-0.94) and use of Endocuff (OR 2.09; 95%CI 1.34-3.27) were independent predictors of adenoma detection rates.

Conclusions: EC increases the adenoma detection rate by 14.7%(95%CI 6.9-22.5%). EC is safe, effective, easy to handle and might reduce colorectal interval carcinomas.

Trial Registration: ClinicalTrials.gov NCT02034929.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0114267PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4255000PMC
December 2015

Prehospital chest emergency sonography trial in Germany: a prospective study.

Eur J Emerg Med 2012 Jun;19(3):161-6

Division of Interdisciplinary Prehospital Emergency Medicine, University Giessen and Marburg, Marburg, Germany.

Objectives: To examine the feasibility and diagnostic value of a novel prehospital chest ultrasound algorithm in patients with dyspnea.

Methods: Sixty-two patients (32 men, 30 women, mean 67.1 years, range 20-90 years) with acute dyspnea prospectively underwent chest sonography with a portable ultrasound device. The algorithm included five sectional views (four-chamber subxyphoidal view, left and right laterodorsal view, left and right anterior intercostal space two to four view) screening for pleural and pericardial effusion, right heart distension, and pneumothorax. The prehospital sonographic findings were confirmed by chest radiograph, ultrasonography, and clinical follow-up in the emergency department.

Results: Prehospital chest emergency sonography trial was completed in 56 patients. Mean examination time was 2 min, and no scan took longer than 5 min. Sonography was easily integrated in the prehospital workflow alongside paramedic treatment without delay of treatment or transport. The most common diagnoses associated with acute dyspnea were (a) acute coronary syndrome (n=12, 21%), (b) decompensated congestive heart failure (CHF) (n=11, 20%), and (c) chronic obstructive pulmonary disease (COPD) (n=10, 18%). Pleural effusion was detected in 100% of CHF, 17% of acute coronary syndrome, and 20% of COPD patients, constituting a highly significant parameter in the differential diagnosis (P<0.01). Ultrasonography provided a helpful tool in n=38 (68%), and additional therapeutic consequences were drawn in n=14 (25%).

Conclusion: Prehospital chest emergency sonography trial is a novel prehospital ultrasound algorithm for patients with dyspnea. Pleural effusion may serve as a novel prehospital marker for patients with decompensated CHF, thus facilitating the often difficult differential diagnosis between CHF and COPD.
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http://dx.doi.org/10.1097/MEJ.0b013e328349edccDOI Listing
June 2012

NFAT-induced histone acetylation relay switch promotes c-Myc-dependent growth in pancreatic cancer cells.

Gastroenterology 2010 Mar 6;138(3):1189-99.e1-2. Epub 2009 Nov 6.

Department of Gastroenterology and Endocrinology, Philipps-University of Marburg, 35043 Marburg, Germany.

Background & Aims: Induction of immediate early transcription factors (ITF) represents the first transcriptional program controlling mitogen-stimulated cell cycle progression in cancer. Here, we examined the transcriptional mechanisms regulating the ITF protein c-Myc and its role in pancreatic cancer growth in vitro and in vivo.

Methods: Expression of ITF proteins was examined by reverse-transcription polymerase chain reaction and immunoblotting, and its implications in cell cycle progression and growth was determined by flow cytometry and [(3)H]-thymidine incorporation. Intracellular Ca(2+) concentrations, calcineurin activity, and cellular nuclear factor of activated T cells (NFAT) distribution were analyzed. Transcription factor complex formations and promoter regulation were examined by immunoprecipitations, reporter gene assays, and chromatin immunoprecipitation. Using a combination of RNA interference knockdown technology and xenograft models, we analyzed the significance for pancreatic cancer tumor growth.

Results: Serum promotes pancreatic cancer growth through induction of the proproliferative NFAT/c-Myc axis. Mechanistically, serum increases intracellular Ca(2+) concentrations and activates the calcineurin/NFAT pathway to induce c-Myc transcription. NFAT binds to a serum responsive element within the proximal promoter, initiates p300-dependent histone acetylation, and creates a local chromatin structure permissive for the inducible recruitment of Ets-like gene (ELK)-1, a protein required for maximal activation of the c-Myc promoter. The functional significance of this novel pathway was emphasized by impaired c-Myc expression, G1 arrest, and reduced tumor growth upon NFAT depletion in vitro and in vivo.

Conclusions: Our study uncovers a novel mechanism regulating cell growth and identifies the NFAT/ELK complex as modulators of early stages of mitogen-stimulated proliferation in pancreatic cancer cells.
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http://dx.doi.org/10.1053/j.gastro.2009.10.045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2895621PMC
March 2010