Publications by authors named "Arne Kandulski"

61 Publications

Hereditary Diffuse Gastric Cancer: Molecular Genetics, Biological Mechanisms and Current Therapeutic Approaches.

Int J Mol Sci 2022 Jul 15;23(14). Epub 2022 Jul 15.

Department and Outpatients Department of Internal Medicine I, University Hospital Regensburg, 93053 Regensburg, Germany.

Hereditary diffuse gastric cancer is an autosomal dominant syndrome characterized by a high prevalence of diffuse gastric cancer and lobular breast cancer. It is caused by inactivating mutations in the tumor suppressor gene . Genetic testing technologies have become more efficient over the years, also enabling the discovery of other susceptibility genes for gastric cancer, such as among the most important genes. The diagnosis of pathogenic variant carriers with an increased risk of developing gastric cancer is a selection process involving a multidisciplinary team. To achieve optimal long-term results, it requires shared decision-making in risk management. In this review, we present a synopsis of the molecular changes and current therapeutic approaches in HDGC based on the current literature.
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http://dx.doi.org/10.3390/ijms23147821DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9319245PMC
July 2022

Simulation of aerosol and droplet spread during upper airway and gastrointestinal endoscopy.

Dig Dis 2022 Jun 23. Epub 2022 Jun 23.

Background And Aims: Aerosols and droplets are the main vectors in transmission of highly contagious SARS-Cov-2. Invasive diagnostic procedures like upper airway and gastrointestinal endoscopy have been declared as aerosol generating procedures. Protection of health care workers is crucial in times of COVID-19 pandemic.

Methods: We simulated aerosol and droplet spread during upper airway and gastrointestinal endoscopy with and without physico-mechanical barriers using a simulation model.

Results: A clear plastic drape as used for central venous access markedly reduced visualized aerosol and droplet spread during endoscopy.

Conclusion: A simple and cheap drape has the potential to reduce aerosol and droplet spread during endoscopy. In terms of health care worker protection, this may be important particularly in low- or moderate-income countries.
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http://dx.doi.org/10.1159/000525482DOI Listing
June 2022

Retrospective evaluation of early thrombosis in transjugular intrahepatic portosystemic polytetrafluoroethylene-coated shunts under 2-day postinterventional heparinization.

Sci Rep 2022 Jun 22;12(1):10506. Epub 2022 Jun 22.

Department of Radiology, University Hospital Regensburg, 93042, Regensburg, Germany.

The development of acute thrombosis within the TIPS tract may be prevented by prophylactic anticoagulation; however, there is no evidence of the correct anticoagulation regimen after TIPS placement. The purpose of this single-center retrospective study was to evaluate the short-term occlusion rate of transjugular intrahepatic portosystemic shunts (TIPSs) with polytetrafluorethylene (PTFE)-coated stents under consequent periprocedural full heparinization (target partial thromboplastin time [PTT]: 60-80 s). We analyzed TIPS placements that were followed up over a six-month period by Doppler ultrasound in 94 patients and compared the study group of 54 patients who received intravenous periprocedural full heparinization (target PTT: 60-80 s) without any other anticoagulation to patients with prolonged anticoagulation medication. The primary endpoint was TIPS patency after six months. The primary patency rate was 88.3% overall, and in the study group, 90.7%, with an early thrombosis rate of 3.2% (study group: 1.9%) and a primary assisted patency rate of 95.7% (study group: 96.3%). In the study group, one case of TIPS thrombosis occurred on the 23rd day after TIPS placement. Two patients underwent reintervention because of stenosis or buckling. Moreover, the target PTT was not attained in 8 of the 54 patent TIPSs. Four patients had an increased portosystemic pressure gradient, without stenosis, and the flow rate was corrected by increasing the TIPS diameter by dilation. Two-day heparinization seems sufficient to avoid early TIPS thrombosis over a six-month period.
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http://dx.doi.org/10.1038/s41598-022-14388-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9217914PMC
June 2022

Quantitative analysis of liver function: 3D variable-flip-angle versus Look-Locker T1 relaxometry in hepatocyte-specific contrast-enhanced liver MRI.

Quant Imaging Med Surg 2022 Apr;12(4):2509-2522

Department of Radiology, University Hospital Regensburg, Regensburg, Germany.

Background: Gd-EOB-DTPA, a liver specific contrast agent with T1- shortening effects, is routinely used in clinical magnetic resonance imaging (MRI) for detection and characterization of focal liver lesions. Gd-EOB-DTPA-enhanced T1 relaxometry has recently received increasing attention as a tool for the quantitative analyses of liver function. However, this T1 relaxometry technique is limited due to various artifacts caused by B1 inhomogeneities and motion artifacts. This study aims to compare two different T1 relaxometry techniques for evaluating liver function as determined using a C-methacetin-based breath test (C-MBT).

Methods: Ninety-six patients underwent gadoxetic acid-enhanced MRI of the liver at 3T and a C-MBT. Two different prototype sequences for T1 relaxometry were used, a 3D VIBE sequence using Dixon water-fat separation and variable-flip-angles (VFA), as well as a 2D Look-Locker sequence (LL). Images were acquired before (T1 pre) and 20 minutes after (T1 post) administration of liver-specific contrast agent to evaluate the reduction rates of T1 relaxation time (rrT1) in accordance with the C-MBT outcome. To analyze both MR sequences' performance, the intraclass correlation coefficient (ICC) between four ROI measurements within the same liver and the coefficient of repeatability (CR) were calculated.

Results: T1 relaxometry measurements based on MR sequences, VFA, and LL show a constant change in line with impaired liver function progression. Simple regression models showed a log-linear correlation of C-MBT values with all evaluated T1 relaxometry measurements (VFA T1post, VFA rrT1, LL T1post, LL rrT1, P<0.001). Both ICC (VFA T1post, LL T1post; 0.75, 0.95) and CR (VFA T1 post, LL T1 post; 179, 101) showed a better agreement between ROI measurements using the LL sequence.

Conclusions: Both T1 relaxometry sequences are suitable for the evaluation of liver function based on C-MBT. However, the Look-Locker sequence is less susceptible to artifacts and might be more advantageous, especially in patients with impaired liver function.
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http://dx.doi.org/10.21037/qims-21-597DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8923846PMC
April 2022

[Beningn disesases of the esophagus].

MMW Fortschr Med 2022 04;164(Suppl 1):20-28

Medizinische Klinik und -Poliklinik II, Medizinische Klinik und -Poliklinik II, Marchioninistr. 15, 81377, München, Germany.

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http://dx.doi.org/10.1007/s15006-022-0829-8DOI Listing
April 2022

Atezolizumab and bevacizumab with transarterial chemoembolization in hepatocellular carcinoma: the DEMAND trial protocol.

Future Oncol 2022 04 27;18(12):1423-1435. Epub 2022 Jan 27.

Department of Medicine II, University Hospital, LMU Munich, Munich, 81377, Germany.

The combination of the anti-PD-L1 antibody atezolizumab and the anti-VEGF bevacizumab is the first approved immunotherapeutic regimen for first-line therapy in patients with unresectable hepatocellular carcinoma (HCC), currently approved in more than 80 countries. The efficacy and tolerability of this regimen suggest that the use of atezolizumab + bevacizumab could be extended to the treatment of patients with intermediate-stage HCC in combination with transarterial chemoembolization (TACE). The authors describe the rationale and design of the DEMAND study. This investigator-initiated, multicenter, randomized phase II study is the first trial to evaluate the safety and efficacy of atezolizumab + bevacizumab prior to or in combination with TACE in patients with intermediate-stage HCC. The primary end point is the 24-month survival rate; secondary end points include objective response rate, progression-free survival, safety and quality of life. Clinical Trial Registration: NCT04224636 (ClinicalTrials.gov).
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http://dx.doi.org/10.2217/fon-2021-1261DOI Listing
April 2022

[Prevention of gastrointestinal cancer].

Z Gastroenterol 2021 Sep 10;59(9):964-982. Epub 2021 Sep 10.

II. Medizinische Klinik, Medizinische Fakultät Mannheim, Universität Heidelberg, Mannheim, Universitätsklinikum Mannheim, Mannheim.

Throughout the past decades, considerable progress has been made in the (early) diagnosis and treatment of gastrointestinal cancers. However, the prognosis for advanced stages of gastrointestinal tumors remains limited for many patients and approximately one third of all tumor patients die as a result of gastrointestinal tumors. The prevention and early detection of gastrointestinal tumors is therefore of great importance.For this reason, we summarize the current state of knowledge and recommendations for the primary, secondary and tertiary prevention of esophageal, stomach, pancreas, liver and colorectal cancer in the following.
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http://dx.doi.org/10.1055/a-1540-7539DOI Listing
September 2021

An investigation of the diagnostic, predictive, and prognostic impacts of three colonic biopsy grading systems for acute graft versus host disease.

PLoS One 2021 26;16(8):e0256543. Epub 2021 Aug 26.

Institute of Pathology, University Medical Center Mainz, Mainz, Germany.

Acute graft versus host disease (aGvHD) is an important, life-threatening complication after allogeneic hematopoietic stem cell transplantation (alloHSCT). To investigate the value of multiple simultaneous colon biopsies in improving diagnostic accuracy in patients with aGvHD, we retrospectively analyzed 157 patients after alloHSCT. The biopsies were evaluated individually using three established histological grading systems (Lerner, Sale, and Melson). The maximum, minimum, median, and mean histological aGvHD grades were calculated for each patient, and the results were correlated with the Glucksberg grade of clinical manifestation of GvHD, steroid therapy status, and outcome. We found that multiple colon biopsies enhanced diagnostic sensitivity. Moreover, higher histological grades correlated with steroid therapy initiation and refractoriness; the latter particularly occurred when advanced damage was present in all samples and healthy colon mucosa was reduced or absent. On multivariate analysis, the minimal Lerner and Glucksberg grades for intestinal aGvHD were significantly associated with steroid treatment failure. Ninety-nine patients died. The median survival was 285 days after the biopsies were taken. Fifteen patients died from relapse of their underling disorder and 84 from other causes, mostly infection (53 patients) and GvHD (14 patients). Multivariate analysis revealed a significant association between none-relapse mortality and the mean Lerner grade, minimum Melson grade, Glucksberg organ stage, and platelet counts. Thus, we found the Lerner system to be superior to the other grading methods in most instances and histologic evaluation of multiple simultaneously obtained biopsies from the colon to result in a higher diagnostic yield, which helps plan systemic steroid treatment while predicting treatment response and outcome.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0256543PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8389423PMC
December 2021

Intraoperative digital single-operator cholangioscopy - extra-anatomical biliary access and insights into severe sclerosing cholangitis in a pediatric patient.

Endoscopy 2022 05 8;54(5):E234-E235. Epub 2021 Jun 8.

Department and Outpatients' Department of Internal Medicine I, University Hospital Regensburg, Germany.

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http://dx.doi.org/10.1055/a-1494-2854DOI Listing
May 2022

Lenvatinib as First-line Treatment of Hepatocellular Carcinoma in Patients with Impaired Liver Function in Advanced Liver Cirrhosis: Real World Data and Experience of a Tertiary Hepatobiliary Center.

J Gastrointestin Liver Dis 2021 06 18;30(2):247-253. Epub 2021 Jun 18.

Department and Outpatients Department of Internal Medicine I, University Hospital Regensburg, Regensburg, Germany.

Background And Aims: Lenvatinib is a multikinase inhibitor approved for systemic first line treatment of hepatocellular cancer (HCC) in patients with compensated liver cirrhosis (LC) and unaltered liver function. We aimed to evaluate the efficiency and tolerability of lenvatinib in patients with HCC in a real world setting, also including patients with advanced LC and impaired liver function.

Methods: Retrospectively, 35 patients with HCC BCLC stages B, C and D were screened. After drop-out and exclusion of patients not receiving active treatment for > 2 weeks, 28 patients (27 male; median age 64.7) with advanced HCC and LC were included in the analysis.

Results: Fourteen patients (male, median age 62.7) treated had Child-Pugh class B LC, while the other 12 patients had a good liver function Child-Pugh class A (male, median age 68.8). Two patients had advanced Child-Pugh class C LC. The patients received an escalating dosing scheme of lenvatinib up to 12 mg/d. The tolerability of lenvatinib was similar in most of the patients, with no significant difference between the subgroups. Median survival was better in patients with Child-Pugh A LC (p=0.003). More than 60% of the patients with Child-Pugh A were still on treatment at the time of data analysis with a median follow-up of 274 ± 117.5 days compared with 153 days (95%CI: 88.3 - 217.7) in patients with Child-Pugh B and 30 days in Child-Pugh C. The survival benefit correlated significantly with less impaired liver function (p=0.003).

Conclusion: Tolerability and toxicity of lenvatinib are similar in patients withChild-Pugh class A and class B LC, but patients with less impaired liver function have a better survival benefit.
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http://dx.doi.org/10.15403/jgld-3345DOI Listing
June 2021

Identification and In-Depth Analysis of the Novel FGFR2-NDC80 Fusion in a Cholangiocarcinoma Patient: Implication for Therapy.

Curr Oncol 2021 03 8;28(2):1161-1169. Epub 2021 Mar 8.

Institute of Pathology, University of Regensburg, 93053 Regensburg, Germany.

Fibroblast growth factor receptor 2 (FGFR2) fusions have emerged as a new therapeutic target for cholangiocarcinoma in clinical practice following the United States Food and Drug Administration (FDA) approval of Pemigatinib in May 2020. FGFR2 fusions can result in a ligand-independent constitutive activation of FGFR2 signaling with a downstream activation of multiple pathways, including the mitogen-activated protein (MAPK) cascade. Until today, only a limited number of fusion partners have been reported, of which the most prevalent is BicC Family RNA Binding Protein (BICC1), representing one-third of all detected FGFR2 fusions. Nonetheless, in the majority of cases rare or yet unreported fusion partners are discovered in next-generation sequencing panels, which confronts clinicians with a challenging decision: Should a therapy be based on these variants or should the course of treatment follow the (limited) standard regime? Here, we present the case of a metastasized intrahepatic cholangiocarcinoma harboring a novel FGFR2-NDC80 fusion, which was discussed in our molecular tumor board. The protein NDC80 kinetochore complex component (NDC80) is an integral part of the outer kinetochore, which is involved in microtubule binding and spindle assembly. For additional therapeutic guidance, an immunohistochemical analysis of the predicted fusion and downstream effector proteins was performed and compared to cholangiocarcinoma samples of a tissue microarray. The FGFR2-NDC80 fusion resulted in strong activation of the FGFR2 signaling pathway. These supporting results led to a treatment recommendation of Pemigatinib. Unfortunately, the patient passed away before the commencement of therapy.
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http://dx.doi.org/10.3390/curroncol28020112DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8025813PMC
March 2021

Novel pathomechanism for spontaneous bacterial peritonitis: disruption of cell junctions by cellular and bacterial proteases.

Gut 2022 03 11;71(3):580-592. Epub 2021 Mar 11.

Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology and Infectious diseases, University Hospital Regensburg, Regensburg, Bavaria, Germany

Objective: Spontaneous bacterial peritonitis (SBP) is a life-threatening complication of liver cirrhosis with a 1-year mortality of 66%. Bacterial translocation (BT) from the intestine to the mesenteric lymph nodes is crucial for the pathogenesis of SBP.

Design: Since BT presupposes a leaky intestinal epithelium, the integrity of mucus and epithelial cell junctions (E-cadherin and occludin) was examined in colonic biopsies from patients with liver cirrhosis and controls. SBP-inducing () and () were isolated from ascites of patients with liver cirrhosis and co-cultured with Caco-2 cells to characterise bacteria-to-cell effects.

Results: SBP-derived and led to a marked reduction of cell-to-cell junctions in a dose-dependent and time-dependent manner. This effect was enhanced by a direct interaction of live bacteria with epithelial cells. Degradation of occludin is mediated via increased ubiquitination by the proteasome. Remarkably, a novel bacterial protease activity is of pivotal importance for the cleavage of E-cadherin.

Conclusion: Patients with liver cirrhosis show a reduced thickness of colonic mucus, which allows bacteria-to-epithelial cell contact. Intestinal bacteria induce degradation of occludin by exploiting the proteasome of epithelial cells. We identified a novel bacterial protease activity of patient-derived SBP-inducing bacteria, which is responsible for the cleavage of E-cadherin structures. Inhibition of this protease activity leads to stabilisation of cell junctions. Thus, targeting these mechanisms by blocking the ubiquitin-proteasome system and/or the bacterial protease activity might interfere with BT and constitute a novel innovative therapeutic strategy to prevent SBP in patients with liver cirrhosis.
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http://dx.doi.org/10.1136/gutjnl-2020-321663DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8862089PMC
March 2022

Diagnostic Accuracy and Therapeutic Efficacy of Digital Single-Operator Cholangioscopy for Biliary Lesions and Stenosis.

Digestion 2021 25;102(5):776-782. Epub 2021 Feb 25.

Department of Internal Medicine I, University Hospital Regensburg, Regensburg, Germany.

Background/aims: Digital single-operator cholangioscopy (dSOC) has revolutionized bile duct visualization. Interventions like electrohydraulic or laser lithotripsy, inspection of suspicious areas, and targeted biopsies have become possible quick and easy. One main indication for dSOC remains the evaluation of indeterminate biliary strictures.

Objective And Methods: We analyzed 180 consecutive dSOCs procedures performed in a high-volume tertiary center to evaluate sensitivity, specificity as well as positive and negative predictive values (PPV and NPV) for indeterminate strictures. Furthermore, technical success and complications were analyzed.

Results: In 92-97%, the region of interest was reached and successfully visualized. In 83-100%, targeted biopsies were obtained from the suspicious area. Only the distal bile duct was less successful with only 84 and 62%, respectively. In general, dSOC procedures were safe. Cholangitis was the main complication. Regarding the diagnostic accuracy of dSOC of indeterminate biliary strictures, we found a sensitivity of 0.87 and specificity of 0.88, over all. Within the whole cohort, the investigators' assessment directly after dSOC had a PPV of 0.63 and a NPV of 0.97. In patients with biliary lesions or stenosis suspicious for malignancy, the dSOC-based visual diagnosis revealed a very high diagnostic accuracy with sensitivity and specificity of 1.0 (95% CI 0.86-1.0) and 0.76 (95% CI 0.56-0.9) with a PPV of 0.77 (95% CI 0.59-0.9) and a high NPV of 1.0 (95% CI 0.85-1.0).

Conclusions: Our study demonstrates that dSOC has a high diagnostic accuracy as well as a favorable safety profile. Therefore, dSOC should be discussed as standard of care during endoscopic retrograde cholangiography for indeterminate biliary lesions.
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http://dx.doi.org/10.1159/000513713DOI Listing
September 2021

Serum Adiponectin Levels Do Not Distinguish Primary from Metastatic Liver Tumors.

Anticancer Res 2020 Jan;40(1):143-151

Department of Internal Medicine I, Regensburg University Hospital, Regensburg, Germany

Background/aim: Adiponectin protects from metabolic disease and cancer. Accordingly, serum adiponectin was reduced in patients with colorectal cancer (CRC). This hepatoprotective factor was definitely increased in hepatocellular carcinoma (HCC). CRC metastases to the liver are common and the aim of the present study was to evaluate whether serum adiponectin discriminates primary from secondary liver cancers.

Materials And Methods: Adiponectin was measured by ELISA in the serum of 36 patients with colorectal liver metastases, 32 patients with HCC and 49 patients without cancer.

Results: Serum adiponectin levels were higher in cancer than non-tumor patients. Adiponectin was not related to TNM stage in HCC nor to the levels of serum tumor markers. Moreover, hepatic inflammation and liver fibrosis were not correlated with serum adiponectin levels. Metabolic diseases are associated with low adiponectin and a higher risk of cancer. In HCC, but not in CRC serum, adiponectin was increased in patients with hypertension and hyperuricemia. In this cohort, adiponectin positively correlated with chemerin, an adipokine supposed to contribute to metabolic disturbances.

Conclusion: Serum adiponectin cannot discriminate primary from secondary liver tumors.
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http://dx.doi.org/10.21873/anticanres.13935DOI Listing
January 2020

Endoscopic Necrosectomy of Walled-Off Necrosis following Severe Pancreatitis Using a Hot AxiosTM Stent - A Case Series.

Dig Dis 2019 Nov 14:1-4. Epub 2019 Nov 14.

Department of Gastroenterology, University Hospital Regensburg, Regensburg, Germany.

Background: Walled-off necrosis is a common complication of severe pancreatitis. Guidelines recommend endoscopic transgastric necrosectomy as therapy of choice. Different endoscopic approaches are possible.

Methods: We retrospectively analyzed our series of 9 patients where necrosectomy was performed after application of a lumen-apposing metal stent (LAMS) delivered using a Hot AxiosTM Stent device.

Results: In all 9 cases, the walled-off necrosis resolved completely. Necrosectomy was performed through the LAMS (mean: 5.7 times). Endoscopic necrosectomy was repeated every 3rd-7th day using 10- or 15-mm snares. There were no major complications. Especially, no early or delayed bleeding was seen.

Conclusion: The Hot AxiosTM Stent device is a safe method for necrosectomy of walled-off necrosis. It enables puncture, drainage, and LAMS insertion in a single delivery, followed by several courses of necrosectomy if needed without stent exchange.
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http://dx.doi.org/10.1159/000503991DOI Listing
November 2019

[Therapeutic regimens using monoclonal antibodies in gastroenterology].

Internist (Berl) 2019 Oct;60(10):1043-1058

Klinik und Poliklinik für Innere Medizin I, Universitätsklinikum Regensburg, Franz-Josef-Strauß-Allee 11, 93053, Regensburg, Deutschland.

Therapeutic regimens using monoclonal antibodies have been implemented in clinical daily practice for various gastroenterological diseases, for therapeutic strategies in gastrointestinal (GI) oncology, and infectious diseases of the gastrointestinal tract. The main indications remain the therapy of chronic inflammatory bowel disease and in GI oncology. A new field has opened for targeted therapy with monoclonal antibodies of recurrent Clostridium difficile infection. In the nomenclature of monoclonal antibodies, the endings of the substances indicate the production or degree of "humanization" of the respective antibodies ("umab": fully human, recombinant antibody; "ximab": chimeric antibody with variable murine domain). For chronic inflammatory bowel disease, monoclonal antibodies has been developed to interfere with molecular targets of the inflammatory cascade in the underlying pathogenesis (tumor necrosis factor‑α, interleukin-12 and -23; α4β7-integrins). The development of targeted therapies in the treatment of GI malignancies, monoclonal antibodies has been developed to interfere with substantial pathways of proliferation and apoptosis as well as neoplastic vascularization and neovascularization (e.g., vascular endothelial growth factor [VEGF] and VEGF receptor antibodies, epidermal growth factor receptor antibodies, HER2/neu antibodies). In the current review, we provide a summary of the current applications of monoclonal antibodies in the therapeutic treatment of gastroenterological diseases.
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http://dx.doi.org/10.1007/s00108-019-00682-2DOI Listing
October 2019

Serum Chemerin Does Not Differentiate Colorectal Liver Metastases from Hepatocellular Carcinoma.

Int J Mol Sci 2019 Aug 12;20(16). Epub 2019 Aug 12.

Department of Internal Medicine I, Regensburg University Hospital, 93053 Regensburg, Germany.

The chemoattractant adipokine chemerin is related to the metabolic syndrome, which is a risk factor for different cancers. Recent studies provide evidence that chemerin is an important molecule in colorectal cancer (CRC) and hepatocellular carcinoma (HCC). Serum chemerin is high in CRC patients and low in HCC patients and may serve as a differential diagnostic marker for HCC and liver metastases from CRC. To this end, serum chemerin was measured in 36 patients with CRC metastases, 32 patients with HCC and 49 non-tumor patients by ELISA. Chemerin serum protein levels were, however, similar in the three cohorts. Serum chemerin was higher in hypertensive than normotensive tumor patients but not controls. Cancer patients with hypercholesterolemia or hyperuricemia also had increased serum chemerin. When patients with these comorbidities were excluded from the calculation, chemerin was higher in CRC than HCC patients but did not differ from controls. Chemerin did not correlate with the tumor markers carcinoembryonic antigen, carbohydrate antigen 19-9 and alpha-fetoprotein in both cohorts and was not changed with tumor-node-metastasis stage in HCC. Chemerin was not associated with hepatic fat, liver inflammation and fibrosis. To conclude, systemic chemerin did not discriminate between CRC metastases and HCC. Comorbidities among tumor patients were linked with elevated systemic chemerin.
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http://dx.doi.org/10.3390/ijms20163919DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6719925PMC
August 2019

Accuracy of Different Rapid Urease Tests in Comparison with Histopathology in Patients with Endoscopic Signs of Gastritis.

Digestion 2020 28;101(2):184-190. Epub 2019 Feb 28.

Department of Internal Medicine I, University Hospital Regensburg, Regensburg, Germany,

Background And Aim: According to several guidelines, both invasive and non-invasive tests can be used to detect Helicobacter pylori (H. pylori). Invasive methods include H. pylori culture, histological staining, rapid urease tests (RUTs) and PCR. Non-invasive methods include urease breath test, stool antigen and serum IgG testing. The aim of our study was to compare all commercially available RUTs and histology in Germany.

Material And Methods: One hundred fifty patients were enrolled in our study, irrespective of proton pump inhibitors (PPIs) or antibiotic use. If the results of RUTs and histology were diverging, real-time PCR to detect H. pylori DNA was undertaken.

Results: We detected no differences in the sensitivity or specificity between the different RUTs. In PPI and/or antibiotic-treated patients, RUTs seemed to be more sensitive for the detection of H. pylori infection compared to histology. In addition to the cheaper price of RUTs, they are also quicker to process. We show that histological staining in patients with signs of gastritis is expensive and not necessary, if there are no additional histological questions besides H. pylori status.

Conclusions: In conclusion, we consider RUTs to be cheap and fast alternatives to histology in patients with endoscopic signs of gastritis, independently of whether PPIs or antibiotic are used. Histological evaluation is expensive, time consuming and may be unnecessary in some cases.
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http://dx.doi.org/10.1159/000497810DOI Listing
November 2020

Combined Gastric and Colorectal Cancer Screening-A New Strategy.

Int J Mol Sci 2018 Dec 3;19(12). Epub 2018 Dec 3.

Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke-University of Magdeburg, Leipziger Str. 44, 39120 Magdeburg, Germany.

Background: Our aim was to evaluate the feasibility of a serological assessment of gastric cancer risk in patients undergoing colonoscopy in countries with low-to-moderate incidence rates.

Methods: Serum samples were prospectively collected from 453 patients (>50 years old) undergoing colonoscopies. Of these, 279 (61.6%) also underwent gastroscopy to correlate the results for serum pepsinogen I and II (sPG-I and sPG-II), sPG-I/II ratio, and anti- antibodies with gastric histopathology findings (graded according to the updated Sydney classification and the Operative Link of Gastritis Assessment (OLGA) and the Operative Link for Gastric Intestinal Metaplasia assessment (OLGIM) systems).

Results: was found in 85 patients (30.5%). Chronic atrophic gastritis was diagnosed in 89 (31.9%) patients. High-risk OLGA (III⁻IV) stages were present in 24 patients, and high-risk OLGIM stages were present in 14 patients. There was an inverse correlation of sPG-I with the degree of atrophy and intestinal metaplasia (IM), as well as with the respective OLGA (r = -0.425; < 0.001) and OLGIM (r = -0.303; < 0.001) stages. A pathological sPG-I result was associated with a relative risk (RR) of 12.2 (95% confidence interval: 6.29⁻23.54; < 0.001) for gastric preneoplastic changes.

Conclusions: The assessment of serum pepsinogen allows the identification of patients at increased risk of gastric cancer. A prevention strategy of combining a screening colonoscopy with a serological screening for preneoplastic gastric changes should be considered in the general population.
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http://dx.doi.org/10.3390/ijms19123854DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6321419PMC
December 2018

Diagnostic Investigations of Gastroesophageal Reflux Disease: Who and When to Refer and for What Test?

Visc Med 2018 Apr 20;34(2):97-100. Epub 2018 Apr 20.

Department of Internal Medicine I, University Hospital Regensburg, Regensburg, Germany.

Background: Due to the high prevalence and incidence of patients with gastroesophageal reflux disease (GERD), the diagnostic workup of patients with symptoms of GERD needs to be balanced between empiric antisecretory therapy and further functional assessment including endoscopy and reflux monitoring.

Methods: This article is based on a literature review (PubMed, Medline) using the terms 'gastroesophageal reflux disease' or 'GERD' and 'diagnosis', 'therapy', or 'PPI' with special and critical analysis of the current 'Porto' consensus report.

Results And Conclusions: Further diagnostics are mandatory in case of alarm symptoms as well as atypical or persistent symptoms under adequate therapy with proton pump inhibitors (PPI). In general, the clinical situation needs to be clarified before sending the patients for reflux monitoring. The question is not only when and whom to test but also how to test: or PPI therapy, pH-metry, or combined pH-impedance analysis. These questions have been defined in a recent consensus report of an international panel of experts and are further discussed in this article.
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http://dx.doi.org/10.1159/000488184DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5981635PMC
April 2018

Mucosal Two-Step Pathogenesis in Gastroesophageal Reflux Disease: Repeated Weakly Acidic Stimulation and Activation of Protease-Activated Receptor-2 on Mucosal Interleukin-8 Secretion.

Digestion 2018 19;98(1):19-25. Epub 2018 Apr 19.

Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University Magdeburg, Magdeburg, Germany.

Background: Activation of protease-activated receptor-2 (PAR2) is involved in the mucosal immune pathogenesis of gastroesophageal reflux disease (GERD) that is characterized by proinflammatory cytokines such as interleukin-8 (IL-8). PAR2 activation on epithelial cells induces epithelial IL-8 secretion and initiates mucosal inflammation.

Methods: A human primary esophageal epithelial cell model was established to investigate the effects of repeated stimulation with weakly acidic solutions and subsequent PAR2 activation. After creating a monolayer, cells were incubated under weakly acidic conditions for 7 h followed by 17 h at pH 7.4. This short-term exposure was repeated once. After weakly acidic stimulation, PAR2 activation was achieved by a synthetic agonist at pH 7.4.

Results: After repeated weakly acidic incubation, PAR2 transcript levels were 3.6-fold upregulated (p = 0.001) and IL-8 transcripts were 2.4-fold enhanced (p = 0.034) compared to nonstimulated controls, while IL-8 protein in the cell pellet and supernatant was not increased. Only the additional PAR2 activation upon pH stimulation led to increased IL-8 secretion into the supernatant.

Conclusions: We propose a 2-step mechanism in which repeated weakly acidic exposure leads to the upregulation of epithelial PAR2 expression. The subsequent activation of upregulated PAR2 contributes to the initiation of mucosal inflammation, which underlies the important role of esophageal epithelium in GERD pathogenesis.
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http://dx.doi.org/10.1159/000486480DOI Listing
October 2018

Cholangioscopy-guided electrohydraulic lithotripsy of large bile duct stones through a percutaneous access device.

Endoscopy 2018 05 16;50(5):E111-E112. Epub 2018 Feb 16.

Department of Radiology, University Hospital Regensburg, Regensburg, Germany.

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http://dx.doi.org/10.1055/s-0044-101015DOI Listing
May 2018

Proton-pump inhibitors: understanding the complications and risks.

Nat Rev Gastroenterol Hepatol 2017 Dec 20;14(12):697-710. Epub 2017 Sep 20.

Department of Gastroenterology, Hepatology and Infectious Diseases, Otto von Guericke University Hospital, Leipziger Strasse 44, 39120 Magdeburg, Germany.

Proton-pump inhibitors (PPIs) are the most effective therapy for the full spectrum of gastric-acid-related diseases. However, in the past decade, a steadily increasing list of complications following long-term use of PPIs has been reported. Their potent acid-suppressive action induces several structural and functional changes within the gastric mucosa, including fundic gland polyps, enterochromaffin-like cell hyperplasia and hypergastrinaemia, which can be exaggerated in the presence of Helicobacter pylori infection. As discussed in this Review, most associations of PPIs with severe adverse events are not based on sufficient evidence because of confounding factors and a lack of plausible mechanisms. Thus, a causal relationship remains unproven in most associations, and further studies are needed. Awareness of PPI-associated risks should not lead to anxiety in patients but rather should induce the physician to consider the appropriate dosing and duration of PPI therapy, including long-term monitoring strategies in selected groups of patients because of their individual comorbidities and risk factors.
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http://dx.doi.org/10.1038/nrgastro.2017.117DOI Listing
December 2017

Impact of thoracic surgery on esophageal motor function-Evaluation by high resolution manometry.

J Thorac Dis 2017 Jun;9(6):1557-1564

Department of Pneumology, University Hospital Magdeburg, Magdeburg, Germany.

Background: Alteration of esophageal function is a potential risk factor for postoperative complications in thoracic surgery. This prospective study investigates esophageal motility and function during and after thoracic procedures via high resolution manometry (HRM) and impedance technology with spatiotemporal representation of pressure data.

Methods: Twelve consecutive patients eligible for elective thoracic surgery underwent preoperative and postoperative (48 hours and 7 days) esophageal HRM. Swallowing acts were carried out with 5 mL of water, 10 mL of water and 1 cm bread in physiological posture to evaluate distal contraction integral (DCI). Length and location of contractile integrity breaks were measured by investigators blinded to the form of surgical intervention. The impact of surgical procedures on esophageal motility was quantified according to current Chicago Classification (CC) criteria. Pre-, intra- and postoperative 24-hour multi-channel impedance pH-metry (MII-pH) was performed to further analyze gastroesophageal reflux patterns.

Results: All patients were investigated 48 hours prior to and 7 days after thoracic procedures, with a total of n=675 swallowing acts being included in our study. Increased motility patterns of the tubular esophagus occurred temporally 48 hours postoperatively. DCI 48 hours after surgery increased significantly (5 mL, P=0.049; solid, P=0.014) and returned to baseline values after seven days (5 mL, P=0.039; solid, P=0.039). Break length was significantly reduced 48 hours postoperatively, especially in the proximal esophageal segment (transition zone). Follow-up measurements after another week were comparable to preoperative baseline findings. The perioperative MII-pH measurement showed numerous artifacts caused by intubation and ventilation during surgery also with increasing short and frequent acidic reflux episodes.

Conclusions: Thoracic procedures cause a transient modulation of esophageal peristalsis with postoperative increased contractility of the tubular esophagus, presumably without affecting intraesophageal reflex arcs. Although limited by the number of patients, we can conclude on our data that postoperative esophageal hypomotility is unlikely to promote secondary pulmonary complications.
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http://dx.doi.org/10.21037/jtd.2017.05.43DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5506166PMC
June 2017

Road Map fluoroscopy successfully guides endoscopic interventions in the esophagus.

Endosc Int Open 2017 Jul 5;5(7):E608-E612. Epub 2017 Jul 5.

Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University, Magdeburg, Germany.

Background And Study Aims: Road Map (RM) fluoroscopy is a radiological technique that enables visualization of anatomic structures using image subtraction at peak opacification. RM fluoroscopy has never previously been evaluated for use in endoscopy. The aim of this study was to evaluate the usefulness of RM in guiding endoscopic intervention in the esophagus.

Patients And Methods: This was a monocentric observational trial of consecutive patients with esophageal strictures in a university hospital. Twenty-seven investigations using RM were performed in 24 patients undergoing esophageal endoscopy. Indications for the procedure were balloon dilatation (n = 7 including 2 pneumatic balloon dilatations for treatment of achalasia), bougie dilatation (n = 7) and diagnostic endoscopy (n = 1). In addition, 12 stents, 7 partially covered and 5 fully covered, were placed using RM as a guide for determination of stent length and diameter. Stents were deployed under RM guidance.

Results: In all procedures, RM successfully guided the intervention. Endoscopic control endoscopy confirmed adequate stent placement in all cases.

Conclusion: RM allows permanent and accurate radiographic imaging of stenoses and esophageal anatomic changes. It is an easy and safe method of guiding endoscopic interventions that require radiological imaging.
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http://dx.doi.org/10.1055/s-0043-111719DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5498184PMC
July 2017

Correlation of High-Resolution Manometric Findings with Symptoms of Dysphagia and Endoscopic Features in Adults with Eosinophilic Esophagitis.

Dig Dis 2017 23;35(5):472-477. Epub 2017 Feb 23.

Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University, Magdeburg, Germany.

Background: Eosinophilic esophagitis (EoE) presents with dysphagia, but data about motility patterns using high-resolution manometry (HRM) are rare. We aimed at evaluating esophageal motility patterns in EoE and their correlation to endoscopic and dysphagia scores.

Methods: Twenty-six EoE patients and 23 controls were included after 4 weeks of treatment with proton pump inhibitors. Dysphagia and endoscopic scores were evaluated before performing HRM. EoE patients were classified to have fibrostenotic (FS) or inflammatory (IF) type. HRM analysis was performed according to the Chicago classification (CC) system.

Results: According to the CC, the HRM findings in EoE and controls were normal in 11 (42%) and 20 (88.5%), p < 0.0001. Weak and failed peristaltic integrity was only seen in EoE patients (failed 1/2.7%, weak 7/26.9%, p = 0.004). Of the EoE patients, 17 had IF and 9 presented with FS type. HRM parameters showed no differences according to the EoE subtype. The endoscopic score in the FS subtype was significantly higher than in EoE with IF subtype (5.33 vs. 3.58, p = 0.001). No significant difference was seen in dysphagia scores in EoE subtypes.

Discussion: HRM findings in EoE are often diagnostic, but they are non-specific and do not correlate with the severity of dysphagia or endoscopic appearance. The clinical impact of HRM in EoE needs further evaluation.
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http://dx.doi.org/10.1159/000458407DOI Listing
December 2017

Helicobacter pylori and non-malignant upper gastrointestinal diseases.

Helicobacter 2016 Sep;21 Suppl 1:30-3

Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University Hospital, Magdeburg, Germany.

Peptic ulcer disease (PUD) has been further decreased over the last decades along with decreasing prevalence of Helicobacter pylori-associated PUD. A delayed H. pylori eradication has been associated with an increased risk of rehospitalization for complicated recurrent peptic ulcer and reemphasized the importance of eradication especially in patients with peptic ulcer bleeding (PUB). PUB associated with NSAID/aspirin intake and H. pylori revealed an additive interaction in gastric pathophysiology which favors the "test-and-treat" strategy for H. pylori in patients with specific risk factors. The H. pylori-negative and NSAID-negative "idiopathic PUD" have been increasingly observed and associated with slower healing tendency, higher risk of recurrence, and greater mortality. Helicobacter pylori-associated dyspepsia has been further investigated and finally defined by the Kyoto consensus. Helicobacter pylori eradication therapy is advised as first option in this group of patients. Only in the case of symptom persistence or recurrence after eradication therapy, dyspeptic patients should be classified as functional dyspepsia (FD). There were few new data in 2015 on the role of H. pylori infection in gastroesophageal reflux disease (GERD), and in particular Barrett's esophagus. A lower prevalence of gastric atrophy with less acid output in patients with erosive esophagitis confirmed previous findings. In patients with erosive esophagitis, no difference was observed in healing rates neither between H. pylori-positive and H. pylori-negative patients nor between patients that underwent eradication therapy compared to patients without eradication. These findings are in line with the current consensus guidelines concluding that H. pylori eradication has no effects on symptoms and does not aggravate preexisting GERD.
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http://dx.doi.org/10.1111/hel.12337DOI Listing
September 2016

Anatomy-shaped design of a fully-covered, biliary, self-expandable metal stent for treatment of benign distal biliary strictures.

Endosc Int Open 2016 Jan 27;4(1):E79-82. Epub 2015 Nov 27.

Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University, Magdeburg, Germany.

Background And Study Aims: The treatment success of benign biliary strictures with fully covered metal stents (CSEMS) is altered by high stent dislocation rates. We aimed to evaluate a new stent design to prevent dislocation.

Patients And Methods: Patients with benign biliary strictures were treated with a newly designed double-coned stent (dcSEMS). Mechanical analysis of the new stent was performed and it was compared with a cylindrical stent.

Results: A total of 13 dcCSEMS were implanted in 11 patients (2 female, 9 male, median age 47, range 33 - 71). All patients had distal biliary strictures due to chronic pancreatitis. No stent migration occurred. In all but one patient the stents were removed. One patient refused stent extraction and was lost to follow up. Stent occlusion occurred twice leading to cholangitis in both cases. The duration of stent treatment was 170 days (range 61 - 254). After extraction only one patient had early recurrent stricture and received the same stent again. Three stents showed minimal tissue granulation at the papilla. One stent presented ingrowth at the proximal end and was removed after implantation of a second fully covered stent. Mechanical examination revealed significantly lower radial expansion force of the new stent as compared to the cylindrical stent.

Conclusions: The new stent design has a low rate of migration. Biomechanical properties may explain this effect.
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http://dx.doi.org/10.1055/s-0034-1393583DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4713183PMC
January 2016

Cone-beam computed tomography - adding a new dimension to ERCP.

Endoscopy 2015 Jul 12;47(7):654-7. Epub 2015 Feb 12.

Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University of Magdeburg, Germany.

Six patients with biliary duct pathologies were investigated with three-dimensional endoscopic retrograde cholangiopancreatography (3D-ERCP). The technique of 3D-ERCP consists of c-arm rotation using a flat detector c-arm to acquire a complete set of images for 3 D visualization of the biliary system. Our case series demonstrates a high level of accuracy with regard to the diagnosis of stenosis and biliary leakage. In two patients the diagnosis obtained from conventional ERCP changed significantly after 3D-ERCP. From these early observations we conclude that 3D-ERCP enhances the diagnostic performance of ERCP in a subset of patients with biliary tract disease.
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http://dx.doi.org/10.1055/s-0034-1391483DOI Listing
July 2015

Esophageal intraluminal baseline impedance differentiates gastroesophageal reflux disease from functional heartburn.

Clin Gastroenterol Hepatol 2015 Jun 9;13(6):1075-81. Epub 2014 Dec 9.

Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University, Magdeburg, Germany.

Background & Aims: Mucosal integrity can be assessed in patients with gastroesophageal reflux disease (GERD) by measuring intraluminal baseline impedance (BI). However, it is not clear whether BI is abnormal in patients with functional heartburn (FH), or can be used to distinguish them from patients with GERD. We compared differences in BI between patients with FH vs GERD.

Methods: We performed a prospective study of 52 patients (16 men; mean age, 55 y; range, 23-78 y) seen at a tertiary university hospital from February 2009 through December 2012. Thirty-five patients had GERD (19 had nonerosive reflux disease [NERD], 16 had erosive reflux disease [ERD]) and 17 had FH. All patients discontinued proton pump inhibitor therapy and then underwent esophagogastroduodenoscopy and multichannel intraluminal impedance and pH monitoring. BI was assessed at 3, 5, 7, 9, 15, and 17 cm proximal to the lower esophageal sphincter in recumbent patients. Biopsy specimens were taken from 3 cm above the gastroesophageal junction; histology analysis was performed to identify and semiquantitatively score (scale, 0-3) dilated intercellular spaces.

Results: Baseline impedance in the distal esophagus was significantly lower in patients with NERD or erosive reflux disease (ERD) than FH (P = .0006). At a cut-off value of less than 2100 Ω, BI measurements identified patients with GERD with 78% sensitivity and 71% specificity, with positive and negative predictive values of 75%. Also in the proximal esophagus, reduced levels of BI levels were found only in patients with ERD. There were negative correlations between level of BI and acid exposure time (r = -0.45; P = .0008), number of acidic reflux episodes (r = -0.45; P = .001), and proximal extent (r = -0.40; P = .004). Biopsy specimens from patients with NERD or ERD had significant increases in dilation of intercellular spaces, compared with those from patients with FH; there was an inverse association between dilated intercellular spaces and BI in the distal esophagus (r = -0.28; P = .06).

Conclusions: Measurement of BI in the lower esophagus can differentiate patients with ERD or NERD from patients with FH (78% sensitivity and 71% specificity), and therefore should be considered as a diagnostic tool for patients with proton pump inhibitor-refractory reflux. Low levels of BI are associated with increased exposure to acid and dilation of intercellular spaces, indicating that BI is a marker of mucosal integrity.
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http://dx.doi.org/10.1016/j.cgh.2014.11.033DOI Listing
June 2015
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