Publications by authors named "Thomas Rösch"

172 Publications

Multi-scale fully convolutional neural networks for histopathology image segmentation: From nuclear aberrations to the global tissue architecture.

Med Image Anal 2021 May 18;70:101996. Epub 2021 Feb 18.

Department for Interdisciplinary Endoscopy, Hamburg, Germany.

Histopathologic diagnosis relies on simultaneous integration of information from a broad range of scales, ranging from nuclear aberrations (≈O(0.1μm)) through cellular structures (≈O(10μm)) to the global tissue architecture (⪆O(1mm)). To explicitly mimic how human pathologists combine multi-scale information, we introduce a family of multi-encoder fully-convolutional neural networks with deep fusion. We present a simple block for merging model paths with differing spatial scales in a spatial relationship-preserving fashion, which can readily be included in standard encoder-decoder networks. Additionally, a context classification gate block is proposed as an alternative for the incorporation of global context. Our experiments were performed on three publicly available whole-slide images of recent challenges (PAIP 2019: hepatocellular carcinoma segmentation; BACH 2020: breast cancer segmentation; CAMELYON 2016: metastasis detection in lymph nodes). The multi-scale architectures consistently outperformed the baseline single-scale U-Nets by a large margin. They benefit from local as well as global context and particularly a combination of both. If feature maps from different scales are fused, doing so in a manner preserving spatial relationships was found to be beneficial. Deep guidance by a context classification loss appeared to improve model training at low computational costs. All multi-scale models had a reduced GPU memory footprint compared to ensembles of individual U-Nets trained on different image scales. Additional path fusions were shown to be possible at low computational cost, opening up possibilities for further, systematic and task-specific architecture optimisation. The findings demonstrate the potential of the presented family of human-inspired, end-to-end trainable, multi-scale multi-encoder fully-convolutional neural networks to improve deep histopathologic diagnosis by extensive integration of largely different spatial scales.
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http://dx.doi.org/10.1016/j.media.2021.101996DOI Listing
May 2021

Laparoscopic lymph node sampling: a new concept for patients with high-risk early esophagogastric junction cancer resected endoscopically.

Gastrointest Endosc 2021 Feb 24. Epub 2021 Feb 24.

Interdisciplinary Endoscopy, University Hospital Hamburg-Eppendorf, Hamburg, Germany.

Background And Aims: Endoscopic resection is considered as curative treatment for early upper GI cancers under certain histologic (low-risk) criteria. In tumors not completely fulfilling these criteria but resected R0 endoscopically, esophagectomy is still advised due to an increased risk of lymph node (LN) metastases. However, the benefit-risk ratio especially in elderly patients at higher risk for radical surgery can be debated. We now present the outcome of our case series of laparoscopic lymph node sampling (LLS) in patients with T1 esophagogastric junction tumors, which had been completely resected by endoscopy but did not fulfill the low-risk criteria (G1/2, m, L0, V0).

Methods: Retrospective review of all T1 cancer cases undergoing LLS with at least one high-risk parameter after endoscopic resection during an 8-year period. Repeated endoscopy with biopsy and abdominothoracic CT had been performed before. Cases were divided into 2 periods, before (n=8) and after (n=12) introduction of an extended LLS protocol (additional resection of the left gastric artery). In case of positive LN, patients underwent conventional oncologic surgery; if negative, follow-up was performed. Main outcome was the number of harvested LN by means of LLS and the percentage of positive LNs found.

Results: 20 patients with cardia (n=1) and distal esophageal/Barrett's cancer (n=19) were included. The LN rate using the extended LLS technique increased by 12 % (period 1: median 12 (range 5-19; 95% CI, 3.4-15.4) vs period 2: median 17.5 (range 12-40; 95% CI, 12.8-22.2; p=0.013). There were 2 adverse events, 1 inadvertent chest tube removal, and 1 postoperative pneumonia. In 15% of cases patients had positive lymph nodes and in 2 cases there was local recurrence at the endoscopic resection site, all necessitating surgery.

Conclusion: An extended technique of laparoscopic lymph node sampling appears to provide adequate LN numbers and is a safe approach with short hospital stay only. Only long-term follow-up of larger patient numbers will allow conclusions about miss rate as well as oncologic adequacy of this concept.
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http://dx.doi.org/10.1016/j.gie.2021.02.014DOI Listing
February 2021

Possible tumour cell reimplantation during curative endoscopic therapy of superficial Barrett's carcinoma.

Gut 2021 Jan 13. Epub 2021 Jan 13.

Department of Interdisciplinary Endoscopy, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

Background And Aims: Endoscopic resection has been established as curative therapy for superficial cancer arising from Barrett's oesophagus (BE); recurrences are very rare. Based on a case series with unusual and massive early recurrences, we analyse the issue of tumour cell reimplantation.

Methods: This hypothesis was developed on the basis of two out of seven patients treated by circumferential (n=6) or nearly circumferential (n=1) en bloc and R0 endoscopic resection of T1 neoplastic BE. Subsequently, a prospective histocytological analysis of endoscope channels and accessories was performed in 2 phases (cytohistological analysis; test for cell viability) in 22 different oesophageal carcinoma patients undergoing endoscopy. Finally, cultures from two oesophageal adenocarcinoma cell lines were incubated with different triamcinolone concentrations (0.625-10 mg/mL); cell growth was determined on a Multiwell plate reader.

Results: Cancer regrowth in the two suspicious cases (male, 78/71 years) occurred 7 and 1 months, respectively, after curative tumour resection. Subsequent surgery showed advanced tumours (T2) with lymph node metastases; one patient died. On cytohistological examinations of channels and accessories, suspicious/neoplastic cells were found in 4/10 superficial and in all 5 advanced cancers. Further analyses in seven further advanced adenocarcinoma cases showed viable cells in two channel washing specimens. Finally, cell culture experiments demonstrated enhanced tumour cell growth by triamcinolone after 24 hours compared with controls.

Conclusions: Tumour cell reimplanation from contaminated endoscopes and accessories is a possible cause of local recurrence after curative endoscopic therapy for superficial Barrett carcinoma; also, corticosteroid injection could have promoted tumour regrowth in these cases.
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http://dx.doi.org/10.1136/gutjnl-2020-322723DOI Listing
January 2021

Germline variation in the insulin-like growth factor pathway and risk of Barrett's esophagus and esophageal adenocarcinoma.

Carcinogenesis 2020 Dec 10. Epub 2020 Dec 10.

Department of Cancer Prevention and Control, Roswell Park Comprehensive Cancer Center, Buffalo, New York, USA.

Genome-wide association studies (GWAS) of esophageal adenocarcinoma (EAC) and its precursor, Barrett's esophagus (BE), have uncovered significant genetic components of risk, but most heritability remains unexplained. Targeted assessment of genetic variation in biologically relevant pathways using novel analytical approaches may identify missed susceptibility signals. Central obesity, a key BE/EAC risk factor, is linked to systemic inflammation, altered hormonal signaling, and insulin-like growth factor (IGF) axis dysfunction. Here, we assessed IGF-related genetic variation and risk of BE and EAC. Principal components analysis (PCA) was employed to evaluate pathway-level and gene-level associations with BE/EAC, using genotypes for 270 SNPs in or near 12 IGF-related genes, ascertained from 3295 BE cases, 2515 EAC cases, and 3207 controls in the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON) GWAS. Gene-level signals were assessed using Multi-marker Analysis of GenoMic Annotation (MAGMA) and SNP summary statistics from BEACON and an expanded GWAS meta-analysis (6167 BE cases, 4112 EAC cases, 17,159 controls). Global variation in the IGF pathway was associated with risk of BE (P=0.0015). Gene-level associations with BE were observed for GHR (growth hormone receptor; p=0.00046, FDR q=0.0056) and IGF1R (IGF1 receptor; p=0.0090, q=0.0542). These gene-level signals remained significant at q<0.1 when assessed using data from the largest available BE/EAC GWAS meta-analysis. No significant associations were observed for EAC. This study represents the most comprehensive evaluation to date of inherited genetic variation in the IGF pathway and BE/EAC risk, providing novel evidence that variation in two genes encoding cell-surface receptors, GHR and IGF1R, may influence risk of BE.
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http://dx.doi.org/10.1093/carcin/bgaa132DOI Listing
December 2020

PAIP 2019: Liver cancer segmentation challenge.

Med Image Anal 2021 01 8;67:101854. Epub 2020 Oct 8.

Department of Biomedical Engineering, Seoul National University Hospital, Seoul, South Korea. Electronic address:

Pathology Artificial Intelligence Platform (PAIP) is a free research platform in support of pathological artificial intelligence (AI). The main goal of the platform is to construct a high-quality pathology learning data set that will allow greater accessibility. The PAIP Liver Cancer Segmentation Challenge, organized in conjunction with the Medical Image Computing and Computer Assisted Intervention Society (MICCAI 2019), is the first image analysis challenge to apply PAIP datasets. The goal of the challenge was to evaluate new and existing algorithms for automated detection of liver cancer in whole-slide images (WSIs). Additionally, the PAIP of this year attempted to address potential future problems of AI applicability in clinical settings. In the challenge, participants were asked to use analytical data and statistical metrics to evaluate the performance of automated algorithms in two different tasks. The participants were given the two different tasks: Task 1 involved investigating Liver Cancer Segmentation and Task 2 involved investigating Viable Tumor Burden Estimation. There was a strong correlation between high performance of teams on both tasks, in which teams that performed well on Task 1 also performed well on Task 2. After evaluation, we summarized the top 11 team's algorithms. We then gave pathological implications on the easily predicted images for cancer segmentation and the challenging images for viable tumor burden estimation. Out of the 231 participants of the PAIP challenge datasets, a total of 64 were submitted from 28 team participants. The submitted algorithms predicted the automatic segmentation on the liver cancer with WSIs to an accuracy of a score estimation of 0.78. The PAIP challenge was created in an effort to combat the lack of research that has been done to address Liver cancer using digital pathology. It remains unclear of how the applicability of AI algorithms created during the challenge can affect clinical diagnoses. However, the results of this dataset and evaluation metric provided has the potential to aid the development and benchmarking of cancer diagnosis and segmentation.
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http://dx.doi.org/10.1016/j.media.2020.101854DOI Listing
January 2021

Prospective evaluation of an assessment tool for technical performance of duodenoscopes.

Dig Endosc 2020 Oct 2. Epub 2020 Oct 2.

Center for Interventional Endoscopy, AdventHealth Orlando, Orlando, Florida, USA.

Objective: While single-use and detachable-tip duodenoscopes have been recently developed to overcome risks of infection transmission, there are no reliable tools to objectively assess their technical performance. We evaluated the reliability and validity of a newly developed tool to assess the technical performance of reusable duodenoscopes.

Methods: An assessment tool was developed to measure duodenoscope performance based on three distinct criteria: maneuverability, mechanical/imaging characteristics and ability to perform requisite interventions. The assessment tool was tested prospectively on duodenoscopes used in endoscopic retrograde cholangiopancreatography (ERCP) procedures at nine academic medical centers over a 6-month period. The main outcome was reliability of the duodenoscope assessment tool, which was estimated using Cronbach's coefficient alpha (α). The secondary outcome was validity of the assessment tool.

Results: The assessment tool evaluated technical performance of reusable duodenoscopes in 1080 ERCP procedures. Indications were biliary in 92.8% and pancreatic in 7.2% procedures. The overall Cronbach's coefficient α for maneuverability was 0.81, assessment of mechanical/imaging characteristics was 0.92, and ability to perform requisite interventions was 0.87. On multiple linear regression analysis, prolonged procedure duration, older patient age and pancreatic interventions were significantly positively associated with higher (worse) scores.

Conclusions: The newly developed assessment tool appears reliable and valid for evaluating the technical performance of duodenoscopes. Registration: ClinicalTrials.gov Identifier: NCT04004533.
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http://dx.doi.org/10.1111/den.13856DOI Listing
October 2020

Sex-Specific Genetic Associations for Barrett's Esophagus and Esophageal Adenocarcinoma.

Gastroenterology 2020 12 9;159(6):2065-2076.e1. Epub 2020 Sep 9.

Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, Texas; Section of Epidemiology and Population Sciences, Department of Medicine, Baylor College of Medicine, Houston, Texas. Electronic address:

Background & Aims: Esophageal adenocarcinoma (EA) and its premalignant lesion, Barrett's esophagus (BE), are characterized by a strong and yet unexplained male predominance (with a male-to-female ratio in EA incidence of up to 6:1). Genome-wide association studies (GWAS) have identified more than 20 susceptibility loci for these conditions. However, potential sex differences in genetic associations with BE/EA remain largely unexplored.

Methods: Given strong genetic overlap, BE and EA cases were combined into a single case group for analysis. These were compared with population-based controls. We performed sex-specific GWAS of BE/EA in 3 separate studies and then used fixed-effects meta-analysis to provide summary estimates for >9 million variants for male and female individuals. A series of downstream analyses were conducted separately in male and female individuals to identify genes associated with BE/EA and the genetic correlations between BE/EA and other traits.

Results: We included 6758 male BE/EA cases, 7489 male controls, 1670 female BE/EA cases, and 6174 female controls. After Bonferroni correction, our meta-analysis of sex-specific GWAS identified 1 variant at chromosome 6q11.1 (rs112894788, KHDRBS2-MTRNR2L9, P = .039) that was statistically significantly associated with BE/EA risk in male individuals only, and 1 variant at chromosome 8p23.1 (rs13259457, PRSS55-RP1L1, P = 0.057) associated, at borderline significance, with BE/EA risk in female individuals only. We also observed strong genetic correlations of BE/EA with gastroesophageal reflux disease in male individuals and obesity in female individuals.

Conclusions: The identified novel sex-specific variants associated with BE/EA could improve the understanding of the genetic architecture of the disease and the reasons for the male predominance.
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http://dx.doi.org/10.1053/j.gastro.2020.08.052DOI Listing
December 2020

Recovery of endoscopy services in the era of COVID-19: recommendations from an international Delphi consensus.

Gut 2020 11 14;69(11):1915-1924. Epub 2020 Aug 14.

Gastroenterology and Endoscopy Unit, Istituto Clinico Humanitas, Milan, Italy.

The COVID-19 pandemic has had a profound impact on provision of endoscopy services globally as staff and real estate were repurposed. As we begin to recover from the pandemic, a cohesive international approach is needed, and guidance on how to resume endoscopy services safely to avoid unintended harm from diagnostic delays. The aim of these guidelines is to provide consensus recommendations that clinicians can use to facilitate the swift and safe resumption of endoscopy services. An evidence-based literature review was carried out on the various strategies used globally to manage endoscopy during the COVID-19 pandemic and control infection. A modified Delphi process involving international endoscopy experts was used to agree on the consensus statements. A threshold of 80% agreement was used to establish consensus for each statement. 27 of 30 statements achieved consensus after two rounds of voting by 34 experts. The statements were categorised as pre-endoscopy, during endoscopy and postendoscopy addressing relevant areas of practice, such as screening, personal protective equipment, appropriate environments for endoscopy and infection control precautions, particularly in areas of high disease prevalence. Recommendations for testing of patients and for healthcare workers, appropriate locations of donning and doffing areas and social distancing measures before endoscopy are unique and not dealt with by any other guidelines. This international consensus using a modified Delphi method to produce a series of best practice recommendations to aid the safe resumption of endoscopy services globally in the era of COVID-19.
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http://dx.doi.org/10.1136/gutjnl-2020-322329DOI Listing
November 2020

Recognizing Post-Endoscopy Complications: A Database Filter Reduces Quality Assurance Workload for Inpatients.

Dig Dis 2021 10;39(2):171-178. Epub 2020 Aug 10.

Department of Interdisciplinary Endoscopy, University Hospital Hamburg-Eppendorf, Hamburg, Germany.

Background And Aims: Documentation of complications of gastrointestinal endoscopy within the commonly used endoscopy documentation systems are mostly limited to acute complications during endoscopy included in the post-procedural endoscopy report. We tested a documentation system-based filter to reduce the workload by maintaining a high sensitivity to recognize post-endoscopy complications.

Methods: Of all inpatient endoscopic resections during 1 year and all endoscopic retrograde cholangiopancreatography (ERCP) procedures during 4 months in 1 tertiary referral centre, post-procedural complications during hospital stay were individually analyzed retrospectively from the hospital databases (gold standard). In comparison, information technology-based filters were assessed searching for specific tests and data within 2 days after endoscopy and/or until discharge. These were second endoscopy, surgery, or an abdominal computed tomography (CT) or haemoglobin drop ≥2 g/dL for endoscopic resection. For ERCP cases, any case with lipase determination and post-ERCP CT scan was selected. Main outcomes were the sensitivity of these filters to recognize post-endoscopy complications and the percentage of workload reduction.

Results: Three hundred twenty-two inpatients who underwent endoscopic resections and 302 ERCP cases (all inpatients) were included. Post-endoscopy complications occurred in 7.14% (endoscopic resection) and 3.7% (ERCP). The above-mentioned filters identified 100% of all resection and post-ERCP complications compared to detailed case file analysis, at the same time reducing the quality management workload to 14 and 31%, respectively.

Conclusions: Post-procedural monitoring of advanced endoscopic procedures performed on inpatient procedures has a high sensitivity (100%) and reduces case-by-case screening workload for complications by 70-85%. Outpatient interventions, however, require a different system for monitoring of post-endoscopy complications after discharge.
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http://dx.doi.org/10.1159/000510757DOI Listing
April 2021

A feasibility study of zebrafish embryo irradiation with laser-accelerated protons.

Rev Sci Instrum 2020 Jun;91(6):063303

Department of Medical Physics, Faculty of Physics, Ludwig-Maximilians-Universität München, 85748 Garching bei München, Germany.

The development from single shot basic laser plasma interaction research toward experiments in which repetition rated laser-driven ion sources can be applied requires technological improvements. For example, in the case of radio-biological experiments, irradiation duration and reproducible controlled conditions are important for performing studies with a large number of samples. We present important technological advancements of recent years at the ATLAS 300 laser in Garching near Munich since our last radiation biology experiment. Improvements range from target positioning over proton transport and diagnostics to specimen handling. Exemplarily, we show the current capabilities by performing an application oriented experiment employing the zebrafish embryo model as a living vertebrate organism for laser-driven proton irradiation. The size, intensity, and energy of the laser-driven proton bunches resulted in evaluable partial body changes in the small (<1 mm) embryos, confirming the feasibility of the experimental system. The outcomes of this first study show both the appropriateness of the current capabilities and the required improvements of our laser-driven proton source for in vivo biological experiments, in particular the need for accurate, spatially resolved single bunch dosimetry and image guidance.
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http://dx.doi.org/10.1063/5.0008512DOI Listing
June 2020

Histologic and Clinical Effects of Different Topical Corticosteroids for Eosinophilic Esophagitis: Lessons from an Updated Meta-Analysis of Placebo-Controlled Randomized Trials.

Digestion 2020 Jul 1:1-9. Epub 2020 Jul 1.

Institute of Medical Biometry and Epidemiology, University Hospital Hamburg-Eppendorf, Hamburg, Germany.

Background: Topical corticosteroids (TS) have become standard therapy for eosinophilic esophagitis (EoE). However, a variety of drug formulations have been used for which results of histological and clinical responses may be different. We aimed at determining the short-term histologic efficacy of TS for EoE based on randomized placebo-controlled trials and to review clinical response.

Methods: We searched MEDLINE, ISI Web of Science, and clinicaltrials.gov for randomized controlled trials (RCTs) on TS versus placebo for active EoE published until June 2019. Treatment effects were calculated as risk ratios (RRs) comparing histologic remission between groups.

Results: Nine RCTs (6 budesonide and 3 fluticasone) involving a total of 483 participants were included. A substantial overall effect of TS on acute histologic remission (RR 12.5, 95% confidence interval 6.0-25.9) was found despite varying definitions of histologic response. Indirect comparisons between drug and formulation types showed a trend for a better histologic efficacy of budesonide (RR 13.5 vs. 10.4 fluticasone) and for the orodispersible tablet (RR 46.2 vs. 11.5 suspension, and 10.4 nebulized formula/spray), but only based on small patient numbers. Scores used for clinical response assessment were different between studies, and short-term clinical results were less impressive: significant differences favoring TS were found in 4/9 RCTs (4/6 budesonide, 0/3 fluticasone).

Conclusions: TS are effective for short-term induction of histological remission in EoE with less impressive clinical response rates. The mode of drug delivery to the esophagus may be a relevant factor for the degree of histologic remission. Further trials should use uniform assessment criteria and long-term patient-centered outcomes.
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http://dx.doi.org/10.1159/000507571DOI Listing
July 2020

Performance of artificial intelligence in colonoscopy for adenoma and polyp detection: a systematic review and meta-analysis.

Gastrointest Endosc 2021 Jan 26;93(1):77-85.e6. Epub 2020 Jun 26.

Endoscopy Unit, Humanitas Clinical and Research Center-IRCCS, Rozzano, Italy; Department of Biomedical Sciences, Humanitas University, Rozzano, Italy.

Background And Aims: One-fourth of colorectal neoplasia are missed at screening colonoscopy, representing the main cause of interval colorectal cancer. Deep learning systems with real-time computer-aided polyp detection (CADe) showed high accuracy in artificial settings, and preliminary randomized controlled trials (RCTs) reported favorable outcomes in the clinical setting. The aim of this meta-analysis was to summarize available RCTs on the performance of CADe systems in colorectal neoplasia detection.

Methods: We searched MEDLINE, EMBASE, and Cochrane Central databases until March 2020 for RCTs reporting diagnostic accuracy of CADe systems in the detection of colorectal neoplasia. The primary outcome was pooled adenoma detection rate (ADR), and secondary outcomes were adenoma per colonoscopy (APC) according to size, morphology, and location; advanced APC; polyp detection rate; polyps per colonoscopy; and sessile serrated lesions per colonoscopy. We calculated risk ratios (RRs), performed subgroup and sensitivity analyses, and assessed heterogeneity and publication bias.

Results: Overall, 5 randomized controlled trials (4354 patients) were included in the final analysis. Pooled ADR was significantly higher in the CADe group than in the control group (791/2163 [36.6%] vs 558/2191 [25.2%]; RR, 1.44; 95% confidence interval [CI], 1.27-1.62; P < .01; I = 42%). APC was also higher in the CADe group compared with control (1249/2163 [.58] vs 779/2191 [.36]; RR, 1.70; 95% CI, 1.53-1.89; P < .01; I = 33%). APC was higher for ≤5-mm (RR, 1.69; 95% CI, 1.48-1.84), 6- to 9-mm (RR, 1.44; 95% CI, 1.19-1.75), and ≥10-mm adenomas (RR, 1.46; 95% CI, 1.04-2.06) and for proximal (RR, 1.59; 95% CI, 1.34-1.88), distal (RR, 1.68; 95% CI, 1.50-1.88), flat (RR, 1.78; 95% CI, 1.47-2.15), and polypoid morphology (RR, 1.54; 95% CI, 1.40-1.68). Regarding histology, CADe resulted in a higher sessile serrated lesion per colonoscopy (RR, 1.52; 95% CI, 1.14-2.02), whereas a nonsignificant trend for advanced ADR was found (RR, 1.35; 95% CI, .74-2.47; P = .33; I = 69%). Level of evidence for RCTs was graded as moderate.

Conclusions: According to available evidence, the incorporation of artificial intelligence as aid for detection of colorectal neoplasia results in a significant increase in the detection of colorectal neoplasia, and such effect is independent from main adenoma characteristics.
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http://dx.doi.org/10.1016/j.gie.2020.06.059DOI Listing
January 2021

IL22BP Mediates the Antitumor Effects of Lymphotoxin Against Colorectal Tumors in Mice and Humans.

Gastroenterology 2020 10 22;159(4):1417-1430.e3. Epub 2020 Jun 22.

Section of Molecular Immunology und Gastroenterology, I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. Electronic address:

Background & Aims: Unregulated activity of interleukin (IL) 22 promotes intestinal tumorigenesis in mice. IL22 binds the antagonist IL22 subunit alpha 2 (IL22RA2, also called IL22BP). We studied whether alterations in IL22BP contribute to colorectal carcinogenesis in humans and mice.

Methods: We obtained tumor and nontumor tissues from patients with colorectal cancer (CRC) and measured levels of cytokines by quantitative polymerase chain reaction, flow cytometry, and immunohistochemistry. We measured levels of Il22bp messenger RNA in colon tissues from wild-type, Tnf, Lta, and Ltb mice. Mice were given azoxymethane and dextran sodium sulfate to induce colitis and associated cancer or intracecal injections of MC38 tumor cells. Some mice were given inhibitors of lymphotoxin beta receptor (LTBR). Intestine tissues were analyzed by single-cell sequencing to identify cell sources of lymphotoxin. We performed immunohistochemistry analysis of colon tissue microarrays from patients with CRC (1475 tissue cores, contained tumor and nontumor tissues) and correlated levels of IL22BP with patient survival times.

Results: Levels of IL22BP were decreased in human colorectal tumors, compared with nontumor tissues, and correlated with levels of lymphotoxin. LTBR signaling was required for expression of IL22BP in colon tissues of mice. Wild-type mice given LTBR inhibitors had an increased tumor burden in both models, but LTBR inhibitors did not increase tumor growth in Il22bp mice. Lymphotoxin directly induced expression of IL22BP in cultured human monocyte-derived dendritic cells via activation of nuclear factor κB. Reduced levels of IL22BP in colorectal tumor tissues were associated with shorter survival times of patients with CRC.

Conclusions: Lymphotoxin signaling regulates expression of IL22BP in colon; levels of IL22BP are reduced in human colorectal tumors, associated with shorter survival times. LTBR signaling regulates expression of IL22BP in colon tumors in mice and cultured human dendritic cells. Patients with colorectal tumors that express low levels of IL22BP might benefit from treatment with an IL22 antagonist.
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http://dx.doi.org/10.1053/j.gastro.2020.06.033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7607422PMC
October 2020

Computer-aided detection-assisted colonoscopy: classification and relevance of false positives.

Gastrointest Endosc 2020 Oct 16;92(4):900-904.e4. Epub 2020 Jun 16.

Humanitas Clinical and Research Center IRCCS, Digestive Endoscopy Unit, Division of Gastroenterology, Rozzano, Milan; Humanitas University, Department of Biomedical Sciences, Pieve Emanuele, Milan, Italy.

Background And Aims: False positive (FP) results by computer-aided detection (CADe) hamper the efficiency of colonoscopy by extending examination time. Our aim was to develop a classification of the causes and clinical relevance of CADe FPs, and to assess the relative distribution of FPs in a real-life setting.

Methods: In a post-hoc analysis of a randomized trial comparing colonoscopy with and without CADe (NCT: 04079478), we extracted 40 CADe colonoscopy videos. Using a modified Delphi process, 4 expert endoscopists identified the main domains for the reasons and clinical relevance of FPs. Then, 2 expert endoscopists manually examined each FP and classified it according to the proposed domains. The analysis was limited to the withdrawal phase.

Results: The 2 main domains for the causes of CADe FPs were identified as artifacts due to either the mucosal wall or bowel content, and clinical relevance was defined as the time spent on FPs and the FP rate per minute. The mean number of FPs per colonoscopy was 27.3 ± 13.1, of which 24 ± 12 (88%) and 3.2 ± 2.6 (12%) were due to artifacts in the bowel wall and bowel content, respectively. Of the 27.3 FPs per colonoscopy, 1.6 (5.7%) required additional exploration time of 4.8 ± 6.2 seconds per FP (ie, 0.7% of the mean withdrawal time). In detail, 15 (24.2%), 33 (53.2%), and 14 (22.6%) FPs were classified as being of mild, moderate, or severe clinical relevance. The rate of FPs per minute of withdrawal time was 2.4 ± 1.2, and was higher for FPs due to artifacts from the bowel wall than for those from bowel content (2.4 ± 0.6 vs 0.3 ± 0.2, P < .001).

Conclusions: FPs by CADe are primarily due to artifacts from the bowel wall. Despite a high frequency, FPs result in a negligible 1% increase in the total withdrawal time because most of them are immediately discarded by the endoscopist.
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http://dx.doi.org/10.1016/j.gie.2020.06.021DOI Listing
October 2020

Cardiovascular dynamics during peroral endoscopic myotomy for esophageal achalasia: a prospective observational study using non-invasive finger cuff-derived pulse wave analysis.

J Clin Monit Comput 2020 Jun 5. Epub 2020 Jun 5.

Department of Anesthesiology, Center of Anesthesiology and Intensive Care Medicine, University Medicine Rostock, Schillingallee 35, 18057, Rostock, Germany.

Peroral endoscopic myotomy (POEM) is natural orifice transluminal endoscopic surgery to treat esophageal achalasia. During POEM, cardiovascular dynamics can be impaired by capnoperitoneum, capnomediastinum, and systemic carbon dioxide accumulation. We systematically investigated changes in cardiovascular dynamics during POEM. We included 31 patients having POEM in this single-center prospective observational study. Before and every 5 min during POEM we measured mean arterial pressure (MAP), heart rate (HR), cardiac index (CI), stroke volume index (SVI), and systemic vascular resistance index (SVRI) using non-invasive finger cuff-derived pulse wave analysis. During POEM, the median MAP was higher than the median baseline MAP of 77 (67;86) mmHg. HR (median at baseline: 67 (60;72) bpm), CI (2.8 (2.5;3.2) L/min/m), SVI (42 (34;51) mL/m), and SVRI (1994 (1652; 2559) dyn × s × cm × m) remained stable during POEM. Mixed model-derived 95% confidence limits of hemodynamic variables during POEM were 72 to 106 mmHg for MAP, 65 to 79 bpm for HR, 2.7 to 3.3 L/min/m for CI, 37 and 46 mL/m for SVI, and 1856 and 2954 dyn × s × cm × m for SVRI. POEM is a safe procedure with regard to cardiovascular dynamics as it does not markedly impair MAP, HR, CI, SVI, or SVRI.
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http://dx.doi.org/10.1007/s10877-020-00541-8DOI Listing
June 2020

Designs of colonoscopic adenoma detection trials: more positive results with tandem than with parallel studies - an analysis of studies on imaging techniques and mechanical devices.

Gut 2021 Feb 14;70(2):268-275. Epub 2020 May 14.

Gastrozentrum Hirslanden, Zurich, Switzerland.

Background And Aims: Adenoma detection rate (ADR) has been shown to correlate with interval cancers after screening colonoscopy and is commonly used as surrogate parameter for its outcome quality. ADR improvements by various techniques have been studied in randomised trials using either parallel or tandem methodololgy.

Methods: A systematic literature search was done on randomised trials (full papers, English language) on tandem or parallel studies using either adenoma miss rates (AMR) or ADR as main outcome to test different novel technologies on imaging (new endoscope generation, narrow band imaging, iScan, Fujinon intelligent chromoendoscopy/blue laser imaging and wide angle scopes) and mechanical devices (transparent caps, endocuff, endorings and balloons). Available meta analyses were also screened for randomised studies.

Results: Overall, 24 randomised tandem trials with AMR (variable definitions and methodology) and 42 parallel studies using ADR (homogeneous methodology) as primary outcome were included. Significant differences in favour of the new method were found in 66.7% of tandem studies (8222 patients) but in only 23.8% of parallel studies (28 059 patients), with higher rates of positive studies for mechanical devices than for imaging methods. In a random-effects model, small absolute risk differences were found, but these were double in magnitude for tandem as compared with parallel studies (imaging: tandem 0.04 (0.01, 0.07), parallel 0.02 (0.00, 0.04); mechanical devices: tandem 0.08 (0.00, 0.15), parallel 0.04 (0.01, 0.07)). Nevertheless, 94.2% of missed adenomas in the tandem studies were small (<1 cm) and/or non-advanced.

Conclusions: A tandem study is more likely to yield positive results than a simple parallel trial; this may be due to the use of different parameters, variable definitions and methodology, and perhaps also a higher likelihood of bias. Therefore, we suggest to accept positive results of tandem studies only if accompanied by positive results from parallel trials.
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http://dx.doi.org/10.1136/gutjnl-2020-320984DOI Listing
February 2021

Efficacy of Real-Time Computer-Aided Detection of Colorectal Neoplasia in a Randomized Trial.

Gastroenterology 2020 08 1;159(2):512-520.e7. Epub 2020 May 1.

Digestive Endoscopy, Nuovo Regina Margherita Hospital, Rome, Italy.

Background & Aims: One-fourth of colorectal neoplasias are missed during screening colonoscopies; these can develop into colorectal cancer (CRC). Deep learning systems allow for real-time computer-aided detection (CADe) of polyps with high accuracy. We performed a multicenter, randomized trial to assess the safety and efficacy of a CADe system in detection of colorectal neoplasias during real-time colonoscopy.

Methods: We analyzed data from 685 subjects (61.32 ± 10.2 years old; 337 men) undergoing screening colonoscopies for CRC, post-polypectomy surveillance, or workup due to positive results from a fecal immunochemical test or signs or symptoms of CRC, at 3 centers in Italy from September through November 2019. Patients were randomly assigned (1:1) to groups who underwent high-definition colonoscopies with the CADe system or without (controls). The CADe system included an artificial intelligence-based medical device (GI-Genius, Medtronic) trained to process colonoscopy images and superimpose them, in real time, on the endoscopy display a green box over suspected lesions. A minimum withdrawal time of 6 minutes was required. Lesions were collected and histopathology findings were used as the reference standard. The primary outcome was adenoma detection rate (ADR, the percentage of patients with at least 1 histologically proven adenoma or carcinoma). Secondary outcomes were adenomas detected per colonoscopy, non-neoplastic resection rate, and withdrawal time.

Results: The ADR was significantly higher in the CADe group (54.8%) than in the control group (40.4%) (relative risk [RR], 1.30; 95% confidence interval [CI], 1.14-1.45). Adenomas detected per colonoscopy were significantly higher in the CADe group (mean, 1.07 ±1.54) than in the control group (mean 0.71 ± 1.20) (incidence rate ratio, 1.46; 95% CI, 1.15-1.86). Adenomas 5 mm or smaller were detected in a significantly higher proportion of subjects in the CADe group (33.7%) than in the control group (26.5%; RR, 1.26; 95% CI, 1.01-1.52), as were adenomas of 6 to 9 mm (detected in 10.6% of subjects in the CADe group vs 5.8% in the control group; RR, 1.78; 95% CI, 1.09-2.86), regardless of morphology or location. There was no significant difference between groups in withdrawal time (417 ± 101 seconds for the CADe group vs 435 ± 149 for controls; P = .1) or proportion of subjects with resection of non-neoplastic lesions (26.0% in the CADe group vs 28.7% of controls; RR, 1.00; 95% CI, 0.90-1.12).

Conclusions: In a multicenter, randomized trial, we found that including CADe in real-time colonoscopy significantly increases ADR and adenomas detected per colonoscopy without increasing withdrawal time. ClinicalTrials.gov no: 04079478.
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http://dx.doi.org/10.1053/j.gastro.2020.04.062DOI Listing
August 2020

Low risk of COVID-19 transmission in GI endoscopy.

Gut 2020 11 22;69(11):1925-1927. Epub 2020 Apr 22.

Interdisciplinary Endoscopy, University Hospital Hamburg Eppendorf Center of Experimental Medicine, Hamburg, Hamburg, Germany.

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http://dx.doi.org/10.1136/gutjnl-2020-321341DOI Listing
November 2020

Waiting times for endotherapy of early malignancy: No problem?

Gastrointest Endosc 2020 08 15;92(2):424-426. Epub 2020 Apr 15.

Department of Interdisciplinary Endoscopy, University Hospital Hamburg-Eppendorf, Hamburg, Germany.

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http://dx.doi.org/10.1016/j.gie.2020.04.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7158833PMC
August 2020

Endoscopic or Surgical Myotomy in Achalasia. Reply.

N Engl J Med 2020 04;382(14):1377-1378

University Hospital Hamburg-Eppendorf, Hamburg, Germany

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http://dx.doi.org/10.1056/NEJMc2000065DOI Listing
April 2020

Pneumatic balloon dilatation versus laparoscopic Heller myotomy for achalasia: a failed attempt at meta-analysis.

Surg Endosc 2021 Feb 16;35(2):602-611. Epub 2020 Mar 16.

Department of Interdisciplinary Endoscopy, University Hospital Hamburg-Eppendorf, Martinistraße 52, 20246, Hamburg, Germany.

Introduction: The advent of peroral endoscopic myotomy (POEM) shed some light on the role of the current standards in the treatment of idiopathic achalasia, namely endoscopic pneumatic dilatation (PD) and laparoscopic Heller myotomy (LHM). We analyzed the quality of the current evidence comparing LHM and PD.

Methods: A systematic literature search was performed in Pubmed/Medline, Web of Science, Google Scholar and Cochrane for meta-analyses/systematic reviews comparing PD and LHM or open surgery, limited to English language full-text articles. After a detailed review of these meta-analyses, all studies included were analyzed further in depth with respect to treatment protocol, assessment of success, complications and sequelae such as gastroesophageal reflux (GER), as well as follow-up details.

Results: Six randomized controlled trials (RCT), 5 with LHM and 1 with open surgery, were found, published in 10 papers. In contrast to a rather homogeneous LHM technique, PD regimens as well as the clinical dysphagia scores were different in every RCT; most RCTs also showed methodological limitations. There were nine meta-analyses which included a variable number of these RCTs or other cohort studies. Meta-analyses between 2009 and 2013 favored surgery, while the 4 most recent ones reached divergent conclusions. The main difference might have been whether repeated dilatation was regarded as part of the PD protocol or as failure.

Conclusions: The variability in PD techniques and in definition of clinical success utilized in the achalasia RCTs on PD versus LHM render the conclusions of meta-analyses unreliable. Further randomized studies should be based on uniform criteria; in the meantime, publication of even more meta-analyses should be avoided.
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http://dx.doi.org/10.1007/s00464-020-07421-xDOI Listing
February 2021

Identification of loci of functional relevance to Barrett's esophagus and esophageal adenocarcinoma: Cross-referencing of expression quantitative trait loci data from disease-relevant tissues with genetic association data.

PLoS One 2019 31;14(12):e0227072. Epub 2019 Dec 31.

Institute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn, Bonn, Germany.

Esophageal adenocarcinoma (EA) and its precancerous condition Barrett's esophagus (BE) are multifactorial diseases with rising prevalence rates in Western populations. A recent meta-analysis of genome-wide association studies (GWAS) data identified 14 BE/EA risk loci located in non-coding genomic regions. Knowledge about the impact of non-coding variation on disease pathology is incomplete and needs further investigation. The aim of the present study was (i) to identify candidate genes of functional relevance to BE/EA at known risk loci and (ii) to find novel risk loci among the suggestively associated variants through the integration of expression quantitative trait loci (eQTL) and genetic association data. eQTL data from two BE/EA-relevant tissues (esophageal mucosa and gastroesophageal junction) generated within the context of the GTEx project were cross-referenced with the GWAS meta-analysis data. Variants representing an eQTL in at least one of the two tissues were categorized into genome-wide significant loci (P < 5×10-8) and novel candidate loci (5×10-8 ≤ P ≤ 5×10-5). To follow up these novel candidate loci, a genetic association study was performed in a replication cohort comprising 1,993 cases and 967 controls followed by a combined analysis with the GWAS meta-analysis data. The cross-referencing of eQTL and genetic data yielded 2,180 variants that represented 25 loci. Among the previously reported genome-wide significant loci, 22 eQTLs were identified in esophageal mucosa and/or gastroesophageal junction tissue. The regulated genes, most of which have not been linked to BE/EA etiology so far, included C2orf43/LDAH, ZFP57, and SLC9A3. Among the novel candidate loci, replication was achieved for two variants (rs7754014, Pcombined = 3.16×10-7 and rs1540, Pcombined = 4.16×10-6) which represent eQTLs for CFDP1 and SLC22A3, respectively. In summary, the present approach identified candidate genes whose expression was regulated by risk variants in disease-relevant tissues. These findings may facilitate the elucidation of BE/EA pathophysiology.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0227072PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6938334PMC
April 2020

Endoscopic or Surgical Myotomy in Patients with Idiopathic Achalasia.

N Engl J Med 2019 12;381(23):2219-2229

From the Departments of Interdisciplinary Endoscopy (Y.B.W., T.N., T.R.), Epidemiology and Statistics (J.F.K.), and General, Visceral, and Thoracic Surgery (O.M., J.I.), University Hospital Hamburg-Eppendorf, and the Department of Surgery, Israelitic Hospital (A.E.), Hamburg, the Department of Surgery, University Hospital Würzburg, Würzburg (B.H.A.R., C.-T.G.), and the Department of Gastroenterology, University Hospital Augsburg, Augsburg (H.M.) - all in Germany; the Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, and the Department of Surgery, Ersta Hospital, Stockholm (B.H.); the Department of Hepatogastroenterology, Institute for Clinical and Experimental Medicine (J.M.), and the 3rd Department of Surgery, 1st Faculty of Medicine, Charles University in Prague and University Hospital Motol (A.P.) - all in Prague, Czech Republic; the Departments of Gastroenterology (A.R.) and Digestive Surgery (U.F.), Istituto Clinico Humanitas Rozzano, and the Department of Digestive Surgery, IRCCS Ospedale San Raffaele (R.R.) - both in Milan; Amsterdam University Medical Centers location AMC, Amsterdam Gastroenterology and Metabolism (A.J.B., P.F.) and Surgery (M.P.S.), University of Amsterdam, Amsterdam; the Department of Gastroenterology and Hepatology, University Hospitals Leuven, and Translational Research Center for Gastrointestinal Disorders, Katholieke Universiteit Leuven, Leuven, Belgium (R.B., G.B.); the Department of Psychology, Harvard University, Cambridge, MA (M.C.V.); and the Division of Gastroenterology, Montreal University Hospital and Research Center, Montreal (D.R.).

Background: Pneumatic dilation and laparoscopic Heller's myotomy (LHM) are established treatments for idiopathic achalasia. Peroral endoscopic myotomy (POEM) is a less invasive therapy with promising early study results.

Methods: In a multicenter, randomized trial, we compared POEM with LHM plus Dor's fundoplication in patients with symptomatic achalasia. The primary end point was clinical success, defined as an Eckardt symptom score of 3 or less (range, 0 to 12, with higher scores indicating more severe symptoms of achalasia) without the use of additional treatments, at the 2-year follow-up; a noninferiority margin of -12.5 percentage points was used in the primary analysis. Secondary end points included adverse events, esophageal function, Gastrointestinal Quality of Life Index score (range, 0 to 144, with higher scores indicating better function), and gastroesophageal reflux.

Results: A total of 221 patients were randomly assigned to undergo either POEM (112 patients) or LHM plus Dor's fundoplication (109 patients). Clinical success at the 2-year follow-up was observed in 83.0% of patients in the POEM group and 81.7% of patients in the LHM group (difference, 1.4 percentage points; 95% confidence interval [CI], -8.7 to 11.4; P = 0.007 for noninferiority). Serious adverse events occurred in 2.7% of patients in the POEM group and 7.3% of patients in the LHM group. Improvement in esophageal function from baseline to 24 months, as assessed by measurement of the integrated relaxation pressure of the lower esophageal sphincter, did not differ significantly between the treatment groups (difference, -0.75 mm Hg; 95% CI, -2.26 to 0.76), nor did improvement in the score on the Gastrointestinal Quality of Life Index (difference, 0.14 points; 95% CI, -4.01 to 4.28). At 3 months, 57% of patients in the POEM group and 20% of patients in the LHM group had reflux esophagitis, as assessed by endoscopy; at 24 months, the corresponding percentages were 44% and 29%.

Conclusions: In this randomized trial, POEM was noninferior to LHM plus Dor's fundoplication in controlling symptoms of achalasia at 2 years. Gastroesophageal reflux was more common among patients who underwent POEM than among those who underwent LHM. (Funded by the European Clinical Research Infrastructure Network and others; ClinicalTrials.gov number, NCT01601678.).
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http://dx.doi.org/10.1056/NEJMoa1905380DOI Listing
December 2019

Improved colorectal anastomotic leakage healing by transanal rinsing treatment after endoscopic vacuum therapy using a novel patient-applied rinsing catheter.

Int J Colorectal Dis 2020 Jan 2;35(1):109-117. Epub 2019 Dec 2.

Department of General, Visceral and Thoracic Surgery, University Hospital Hamburg-Eppendorf, Hamburg, Germany.

Purpose: Anastomotic or stump leakage is a common and serious complication of colorectal surgery. The objective of this study was to retrospectively investigate the clinical use and potential benefit of transanal rinsing treatment (TRT) using an innovative rinsing catheter (RC) after treatment with endoscopic vacuum therapy (EVT).

Methods: Patients with leakage after low colorectal surgery who had been treated with EVT were retrospectively analyzed. A subset of patients was trained to perform TRT with a specially developed RC. We investigated the rate of complete healing of the leakage, septic complications, failure of the therapy, surgical revisions, ostomy closure rate, and complications related to endoscopic therapy.

Results: Between February 2007 and January 2014, 98 patients with local complications after low colorectal surgery, treated with EVT, were identified. Eighty-nine patients were analyzed (the treatment of nine patients was stopped due to medical or technical problems): 31 patients were treated with EVT only (EVT group) and 58 patients with EVT followed by TRT (EVT/TRT group). Complete healing of the leakage was significantly better in the EVT/TRT group [84% vs. 58% (p < 0.009)], and significantly fewer septic complications needing surgical revision were detected [3% vs. 11% (p = 0.001)]. No significant differences regarding endoscopy-related complications and ostomy closure were found between EVT and EVT/TRT patients.

Conclusions: The use of patient-administered TRT with an innovative, customized RC after EVT is technically feasible and reliable and significantly improves therapeutic results. Further prospective trials with larger patient groups are needed to validate the results of our study.
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http://dx.doi.org/10.1007/s00384-019-03456-2DOI Listing
January 2020

Shared Genetic Etiology of Obesity-Related Traits and Barrett's Esophagus/Adenocarcinoma: Insights from Genome-Wide Association Studies.

Cancer Epidemiol Biomarkers Prev 2020 02 20;29(2):427-433. Epub 2019 Nov 20.

Institute of Human Genetics, University of Bonn, Bonn, Germany.

Background: Obesity is a major risk factor for esophageal adenocarcinoma (EA) and its precursor Barrett's esophagus (BE). Research suggests that individuals with high genetic risk to obesity have a higher BE/EA risk. To facilitate understanding of biological factors that lead to progression from BE to EA, the present study investigated the shared genetic background of BE/EA and obesity-related traits.

Methods: Cross-trait linkage disequilibrium score regression was applied to summary statistics from genome-wide association meta-analyses on BE/EA and on obesity traits. Body mass index (BMI) was used as a proxy for general obesity, and waist-to-hip ratio (WHR) for abdominal obesity. For single marker analyses, all genome-wide significant risk alleles for BMI and WHR were compared with summary statistics of the BE/EA meta-analyses.

Results: Sex-combined analyses revealed a significant genetic correlation between BMI and BE/EA ( = 0.13, = 2 × 10) and a of 0.12 between WHR and BE/EA ( = 1 × 10). Sex-specific analyses revealed a pronounced genetic correlation between BMI and EA in females ( = 0.17, = 1.2 × 10), and WHR and EA in males ( = 0.18, = 1.51 × 10). On the single marker level, significant enrichment of concordant effects was observed for BMI and BE/EA risk variants ( = 8.45 × 10) and WHR and BE/EA risk variants ( = 2 × 10).

Conclusions: Our study provides evidence for sex-specific genetic correlations that might reflect specific biological mecha-nisms. The data demonstrate that shared genetic factors are particularly relevant in progression from BE to EA.

Impact: Our study quantifies the genetic correlation between BE/EA and obesity. Further research is now warranted to elucidate these effects and to understand the shared pathophysiology.
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http://dx.doi.org/10.1158/1055-9965.EPI-19-0374DOI Listing
February 2020

Anesthesia for Patients Undergoing Peroral Endoscopic Myotomy Procedures: A Review of the Literature.

Anesth Analg 2020 05;130(5):1331-1340

Department of Anesthesiology, Center of Anesthesiology and Intensive Care Medicine.

Idiopathic achalasia is a motility disorder of the esophagus with important implications on anesthesia and periprocedural management. As new and more complex treatment options develop, anesthesiologists are increasingly involved with these patients. The cardinal symptoms of achalasia are as follows: dysphagia, regurgitation, chest pain, and weight loss. Achalasia is also associated with an increased risk of aspiration. Patients are frequently treated by endoscopic botulinum toxin injections, pneumatic dilation of the lower esophageal sphincter, laparoscopic Heller myotomy, or peroral endoscopic myotomy (POEM). The POEM procedure is based on the concept of "natural orifice transluminal endoscopic surgery." Because the integrity of the esophageal wall is deliberately interrupted during POEM, the mediastinum and the peritoneal cavity may be exposed. Thus, the insufflated carbon dioxide frequently causes hypercapnia, tension capnoperitoneum, capnomediastinum, or pneumothoraces. An interdisciplinary team, skilled in diagnostics and emergency measures such as therapeutic hyperventilation, percutaneous abdominal needle decompression, or pleural drainage, is essential for the successful periprocedural management of POEM. POEM is one endoscopic procedure that requires general anesthesia. But neither anesthesia-specific care algorithms nor evidence-based recommendations are currently available for these patients. Because institutional experience varies broadly across the globe, this review examines anesthesia recommendations and perioperative management of POEM procedures based on 7 retrospective case series, 1 prospective study, and our personal experience.
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http://dx.doi.org/10.1213/ANE.0000000000004420DOI Listing
May 2020

How to Perform a High-Quality PerOral Endoscopic Myotomy?

Gastroenterology 2019 11 9;157(5):1184-1189. Epub 2019 Sep 9.

Digestive Endoscopy Unit, Division of Gastroenterology, Humanitas Research Hospital, Milan, Italy.

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http://dx.doi.org/10.1053/j.gastro.2019.09.001DOI Listing
November 2019

Comparison of the integrin α4β7 expression pattern of memory T cell subsets in HIV infection and ulcerative colitis.

PLoS One 2019 29;14(7):e0220008. Epub 2019 Jul 29.

I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Anti-α4β7 therapy with vedolizumab (VDZ) has been suggested as possible immune intervention in HIV. Relatively little is known about the α4β7-integrin (α4β7) expression of different T-cell subsets in different anatomical compartments of healthy individuals, patients with HIV or inflammatory bowel disease (IBD). Surface expression of α4β7 as well as the frequency of activation, homing and exhaustion markers of T cells were assessed by multicolour flow cytometry in healthy volunteers (n = 15) compared to HIV infected patients (n = 52) or patients diagnosed with ulcerative colitis (UC) (n = 14), 6 of whom treated with vedolizumab. In addition, lymph nodal cells (n = 6), gut-derived cells of healthy volunteers (n = 5) and patients with UC (n = 6) were analysed. Additionally, we studied longitudinal PBMC samples of an HIV patient who was treated with vedolizumab for concomitant UC. Overall, only minor variations of the frequency of α4β7 on total CD4+ T cells were detectable regardless of the disease status or (VDZ) treatment status in peripheral blood and the studied tissues. Peripheral α4β7+ CD4+ T cells of healthy individuals and patients with UC showed a higher activation status and were more frequently CCR5+ than their α4β7- counterparts. Also, the frequency of α4β7+ cells was significantly lower in peripheral blood CD4+ effector memory T cells of HIV-infected compared to healthy individuals and this reduced frequency did not recover in HIV patients on ART. Conversely, the frequency of peripheral blood naïve α4β7+ CD4+ T cells was significantly reduced under VDZ treatment. The results of the current study will contribute to the understanding of the dynamics of α4β7 expression pattern on T cells in HIV and UC and will be useful for future studies investigating VDZ as possible HIV cure strategy.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0220008PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6663001PMC
March 2020

[G-POEM in gastroparesis - another weapon in the armamentarium?]

Z Gastroenterol 2019 Jul 9;57(7):889-891. Epub 2019 Jul 9.

Klinik und Poliklinik für Interdiziplinäre Endoskopie, Universitätsklinikum Hamburg-Eppendorf, Hamburg.

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http://dx.doi.org/10.1055/a-0919-559DOI Listing
July 2019