Publications by authors named "Oliver Mann"

91 Publications

Long-Term Improvement of Chronic Low-Grade Inflammation After Bariatric Surgery.

Obes Surg 2021 Mar 5. Epub 2021 Mar 5.

III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany.

Purpose: Bariatric surgery (BS) was shown to improve inflammatory markers in previous short-term follow-up studies. The aim of the present study was to assess the long-term effects of BS on chronic low-grade inflammation markers related to severe obesity. Moreover, the meaning of the type of BS procedure as well as the remission of type 2 diabetes (T2D) for inflammatory status up to 4 years after BS was analyzed.

Materials And Methods: In a retrospective cohort study including 163 patients at baseline, inflammatory and metabolic parameters were assessed at 4 time points: before surgery (baseline), 6 months after surgery (visit 1), 2 years after surgery (visit 2), and 4 years after surgery (visit 3). Univariate regression analysis was used to identify variables that were thought to determine change in inflammatory parameters.

Results: CRP, hs-CRP, leucocytes, and ferritin significantly declined in the mid- and long-term according to the U-shaped curve of weight loss (p<0.001). Change in body mass index (BMI) at long-time follow-up showed a significant linear effect on change in leucocytes (B=0.082; p<0.001) and change in hs-CRP (B=0.03; p<0.05). There was a strong, positive correlation between T2D and hs-CRP at visit 2 (r=0.195; p<0.05) and visit 3 (r=0.36; p=0.001). With regard to type of surgery and gender, there were no significant differences in inflammatory parameters.

Conclusion: BS is able to reduce obesity-related chronic low-grade inflammation up to 4 years after surgical intervention. The improvement in metaflammation is related to the change in BMI and remission of T2D in the long-term.
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http://dx.doi.org/10.1007/s11695-021-05315-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7934816PMC
March 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

Validation of quantitative assessment of indocyanine green fluorescent imaging in a one-vessel model.

PLoS One 2020 18;15(11):e0240188. Epub 2020 Nov 18.

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

Objectives: Evaluation of intestinal perfusion remains subjective and depends on the surgeon´s individual experience. Intraoperative quality assessment of tissue perfusion with indocyanine green (ICG) fluorescence using a near-infrared camera system has been described in different ways and for different indications. The aim of the present study was to evaluate fluorescent imaging (FI) in the quantitative assessment of intestinal perfusion in a gastric tube model in pigs and to compare the results to results obtained with florescent microspheres (FM), the gold standard for tissue perfusion.

Methods: Seven pigs (56.0±3.0 kg), both males and females, underwent gastric tube formation after transection and ligation of the gastric arteries, except the right gastroepiploic artery, to avoid collateral blood flow. After baseline assessment (T0), hypotension (T1) was induced by propofol (Karampinis et al 2017) (< 60 mmHg). Then, propofol was paused to obtain normotension (T2, Mean arterial pressure (MAP) 60-90 mmHg). Finally, hypertension (T3, MAP>90 mmHg) was induced by norepinephrine. Measurements were performed in three regions of interest (ROIs) under standardized conditions: the fundus (D1), corpus (D2), and prepyloric area (D3). Hemodynamic parameters and transit-time flow measurement (TTFM) in the right gastroepiploic artery were continuously assessed. FI, FM and the partial pressure of tissue oxygen (TpO2) were quantified in each ROI.

Results: The study protocol could successfully be performed during stable hemodynamics. Flow in the gastroepiploic artery measured by transit time flow measurement (TTFM) was related to hemodynamic changes between the measurements, indicating improved blood flow with increasing MAP. The distal part of the gastric tube (D1) showed significantly (p<0.05) impaired perfusion compared to the proximal parts D3 and D2 using FM. ICG-FI also showed the highest values in D3 and the lowest values in D1 at all hemodynamic levels (T1-T3; p<0,05).

Conclusion: Visual and quantitative assessment of gastric tube perfusion is feasible in an experimental setting using ICG-FI. This might be a promising tool for intraoperative assessment during visceral surgery in the future.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0240188PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7673564PMC
December 2020

Bariatric Surgery Is Protective Against Renal Function Decline in Severely Obese Patients in the Long-Term.

Obes Surg 2021 Mar 7;31(3):1038-1045. Epub 2020 Nov 7.

III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany.

Purpose: This study aims to assess the long-term renal effects of bariatric surgery (BS) in severely obese patients over a follow-up period of up to 11 years.

Materials And Methods: In a retrospective cohort study including 102 patients, patients were stratified by eGFR at baseline and divided into three groups: (1) reduced, (2) normal, and (3) increased filtration rate. Adjustments for age- and sex-related decline in eGFR were performed. We used uni- and multivariate regression analysis to identify variables that were thought to determine change in eGFR.

Results: Over a median follow-up of 8.5 years (interquartile range 2.7), eGFR declined from 96.1 ± 20.7 to 84.9 ± 21.0 ml/min (p < 0.001). Among patients with (1), eGFR remained stable (69.1 ± 19.3 ml/min). Among patients with (2), eGFR declined from 99.7 ± 13.3 ml/min to 88.7 ± 19.4 ml/min (p < 0.001). Among patients with (3), eGFR decreased to normal levels (94.2 ± 17.7 ml/min, p < 0.001). Age- and sex-adjusted eGFR increased (6.4 ± 14.4 ml/min; p < 0.05) among patients with reduced filtration rate. Among patients with normal filtration rate, adjusted eGFR remained stable during follow-up (-1.3 ± 15.2 ml/min; n.s.). Among patients with increased filtration rate, adjusted eGFR decreased and remained within the normal range (-13.2 ± 12.2 ml/min; p < 0.001). Change in eGFR showed a negative correlation with eGFR at baseline (B = -0.31; p < 0.001), change in LDL-cholesterol (B = -0.09; p < 0.05), and a negative correlation with treatment requiring hypertension (B = -9.36; p = 0.001).

Conclusion: BS is protective against renal function decline in severely obese patients in the long term.
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http://dx.doi.org/10.1007/s11695-020-05096-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7921037PMC
March 2021

Maternal Brown Fat Thermogenesis Programs Glucose Tolerance in the Male Offspring.

Cell Rep 2020 11;33(5):108351

Institute for Endocrinology and Diabetes-Molecular Endocrinology, Center of Brain Behavior & Metabolism, University of Lübeck, 23562 Lübeck, Germany. Electronic address:

Environmental temperature is a driving factor in evolution, and it is commonly assumed that metabolic adaptations to cold climates are the result of transgenerational selection. Here, we show in mice that even minor changes in maternal thermogenesis alter the metabolic phenotype already in the next generation. Male offspring of mothers genetically lacking brown adipose tissue (BAT) thermogenesis display increased lean mass and improved glucose tolerance as adults, while females are unaffected. The phenotype is replicated in offspring of mothers kept at thermoneutrality; conversely, mothers with higher gestational BAT thermogenesis produce male offspring with reduced lean mass and impaired glucose tolerance. Running-wheel exercise reverses the offspring's metabolic impairments, pointing to the muscle as target of these fetal programming effects. Our data demonstrate that gestational BAT activation negatively affects metabolic health of the male offspring; however, these unfavorable fetal programming effects may be negated by active lifestyle.
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http://dx.doi.org/10.1016/j.celrep.2020.108351DOI Listing
November 2020

The value of CT imaging and CRP quotient for detection of postbariatric complications.

Langenbecks Arch Surg 2021 Feb 17;406(1):181-187. Epub 2020 Sep 17.

Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany.

Background: The diagnosis of major complications seems to be more challenging in obese patients. We aimed to show the relevance of routinely assessed clinical and paraclinical parameters as well as the relevance of CT scans in the diagnosis of major complications after bariatric procedures.

Methods: All patients who underwent operations (primary or revisional) in a 3-year period were retrospectively studied after bariatric surgery with a specific focus on the routinely assessed clinical parameters (tachycardia, temperature), paraclinical parameters on postoperative day (POD) 1 and 3 (C-reactive protein (CRP), leukocytes), and additional computed tomography (CT) scan results for the diagnosis of leakage, bleeding, intraabdominal abscess, superficial abscess, and other complications.

Results: A total of 587 patients were examined. In this cohort, 73 CT scans were performed due to suspected intraabdominal or pulmonary complication according to our hospital standard operating procedure. In total, 14 patients (2.4%) had a major complication (Clavien-Dindo grade IV/V). Of those, 10 patients (1.7%) had postoperative leakage. While the correct leakage diagnosis was only found in 33% of the patients by CT scan, the overall specificity of CT as a diagnostic tool for all kinds of complications remained high. Especially for abscess detection, CT scan showed a sensitivity and specificity of 100%. Multivariate analysis showed a significantly higher risk of leakage development characterized by a doubling of postoperative CRP level (odds ratio 4.84 (95% confidence interval 2.01-11.66, p < 0.001)). To simplify the use of CRP as a predictive factor for the diagnosis of leakage, a cut-off value of 2.4 was determined for the CRP quotient (POD3/POD1) with a sensitivity of 0.88 and a specificity of 0.89.

Conclusion: CT diagnostic after bariatric surgery has a high positive predictive value, especially for intraabdominal abscess formation. Nevertheless, CT scan for the diagnosis of leakage has a low sensitivity. Thus, a negative CT scan does not exclude the presence of a leakage. Using the described CRP quotient with a cut-off of 2.4, the risk of early leakage can be easily estimated. Furthermore, in any uncertain case of clinically suspected leakage, diagnostic laparoscopy should be performed.
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http://dx.doi.org/10.1007/s00423-020-01986-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7870754PMC
February 2021

Multi-layered epigenetic regulation of IRS2 expression in the liver of obese individuals with type 2 diabetes.

Diabetologia 2020 10 24;63(10):2182-2193. Epub 2020 Jul 24.

First Department of Medicine, Division of Epigenetics and Metabolism, University of Lübeck, Ratzeburger Allee 160, 23562, Lübeck, Germany.

Aims/hypothesis: IRS2 is an important molecular switch that mediates insulin signalling in the liver. IRS2 dysregulation is responsible for the phenomenon of selective insulin resistance that is observed in type 2 diabetes. We hypothesise that epigenetic mechanisms are involved in the regulation of IRS2 in the liver of obese and type 2 diabetic individuals.

Methods: DNA methylation of seven CpG sites was studied by bisulphite pyrosequencing and mRNA and microRNA (miRNA) expression was assessed by quantitative real-time PCR in liver biopsies of 50 obese non-diabetic and 31 obese type 2 diabetic participants, in a cross-sectional setting. Methylation-sensitive luciferase assays and electrophoretic mobility shift assays were performed. Furthermore, HepG2 cells were treated with insulin and high glucose concentrations to induce miRNA expression and IRS2 downregulation.

Results: We found a significant downregulation of IRS2 expression in the liver of obese individuals with type 2 diabetes (0.84 ± 0.08-fold change; p = 0.0833; adjusted p value [p] = 0.0417; n = 31) in comparison with non-diabetic obese participants (n = 50). This downregulation correlated with hepatic IRS2 DNA methylation at CpG5. Additionally, CpG6, which is located in intron 1 of IRS2, was hypomethylated in type 2 diabetes; this site spans the sterol regulatory element binding transcription factor 1 (SREBF1) recognition motif, which likely acts as transcriptional repressor. The adjacent polymorphism rs4547213 (G>A) was significantly associated with DNA methylation at a specificity-protein-1 (SP1) binding site (CpG3). Moreover, DNA methylation of cg25924746, a CpG site located in the shore region of the IRS2 promoter-associated CpG island, was increased in the liver of individuals with type 2 diabetes, as compared with those without diabetes. A second epigenetic mechanism, upregulation of hepatic miRNA hsa-let-7e-5p (let-7e-5p) in obese individuals with type 2 diabetes (n = 29) vs non-diabetic obese individuals (n = 49) (1.2 ± 0.08-fold change; p = 0.0332; p = 0.0450), is likely to act synergistically with altered IRS2 DNA methylation to decrease IRS2 expression. Mechanistic in vitro experiments demonstrated an acute upregulation of let-7e-5p expression and simultaneous IRS2 downregulation in a liver (HepG2) cell line upon hyperinsulinaemic and hyperglycaemic conditions.

Conclusions/interpretation: Our study highlights a new multi-layered epigenetic network that could be involved in subtle dysregulation of IRS2 in the liver of individuals with type 2 diabetes. This might lead to fine-tuning of IRS2 expression and is likely to be supplementary to the already known factors regulating IRS2 expression. Thereby, our findings could support the discovery of new diagnostic and therapeutic strategies for type 2 diabetes. Graphical abstract.
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http://dx.doi.org/10.1007/s00125-020-05212-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7476982PMC
October 2020

Epigenetic Downregulation of FASN in Visceral Adipose Tissue of Insulin Resistant Subjects.

Exp Clin Endocrinol Diabetes 2020 May 20. Epub 2020 May 20.

First Medical Department, University of Lübeck, Lübeck, Germany.

Objective: The risk to develop type 2 diabetes increases with the amount of visceral adiposity presumably due to increased lipolysis and subsequent lipid accumulation in visceral organs. However, data describing the molecular regulation of these pathways in humans are rare. We tested if genes of the lipogenic and lipolytic pathways are associated with glucose intolerance independently of obesity in visceral adipose tissue (VAT) of obese subjects. Moreover, we studied DNA methylation of ( that catalyses the synthesis of long-chain fatty acids, in VAT of the same subjects and whether it is associated with metabolic traits.

Subjects And Methods: Visceral adipose tissue biopsies and blood samples were taken from 93 severely obese subjects undergoing bariatric surgery. Subjects were grouped in low HbA1c (L-HbA1c, HbA1c<6.5 %) and high HbA1c (H-HbA1c, HbA1c≥6.5 %) groups and expression of genes from the lipogenic and lipolytic pathways was analysed by TaqMan qPCR. DNA methylation of was quantified by bisulfite-pyrosequencing.

Results: expression was downregulated in visceral fat from subjects with high HbA1c (p = 0.00009). Expression of other lipogenetic (, ) or lipolytic genes (, ) and was not changed. DNA methylation of was increased at a regulatory ChoRE recognition site in the H-HbA1c-subgroup and correlated negatively with mRNA (r = - 0.302, p = 0.0034) and positively with HbA1c (r = 0.296, p = 0.0040) and blood glucose (r = 0.363, p = 0.0005).

Conclusions: Epigenetic downregulation of in visceral adipose tissue of obese subjects might contribute to limited lipogenesis of important insulin sensitizing fatty acids and could thereby contribute to glucose intolerance and the development of type 2 diabetes independently of obesity.
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http://dx.doi.org/10.1055/a-1150-7446DOI Listing
May 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

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

Anti-inflammatory microenvironment of esophageal adenocarcinomas negatively impacts survival.

Cancer Immunol Immunother 2020 Jun 25;69(6):1043-1056. Epub 2020 Feb 25.

Section of Molecular Immunology and Gastroenterology, Center of Internal Medicine, I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany.

Objective: Reflux promotes esophageal adenocarcinomas (EACs) creating a chronic inflammatory environment. Survival rates are low due to early local recurrences and distant metastasis. Hence, there is a need for new potential treatment options like immunotherapies. However, the inflammatory microenvironment in EACs and its impact on patient outcome remain to be fully understood.

Methods: mRNA expression levels of pro- and anti-inflammatory markers in 39 EAC patients without neoadjuvant radio-chemotherapy were measured. Data were confirmed using flow cytometric analysis of freshly resected surgical specimens. Inflammatory alterations in premalignant lesions of Barrett's esophagus were analyzed by immunohistochemistry.

Results: Expression levels of IL22 were reduced in EAC, while expression levels of FOXP3, IL10 and CTLA4 were increased. Flow cytometry demonstrated a strong infiltration of CD4 T cells with a reduction in CD4 T cells producing IL-22 or IL-17A. We also observed an increase in CD4CD127FOXP3 cells producing IL-10. Accumulation of FOXP3 T cells occurred prior to malignant changes. High expression of IL10 and low expression of IL22 in EAC were associated with reduced overall survival. Moreover, increased expression of IL10, CTLA4 and PD1 in the unaltered esophageal mucosa distant to the EAC was also linked with an unfavorable prognosis.

Conclusion: EAC shows an anti-inflammatory environment, which strongly affects patient survival. The microscopically unaltered peritumoral tissue shows a similar anti-inflammatory pattern indicating an immunological field effect, which might contribute to early local recurrences despite radical resection. These data suggest that using checkpoint inhibitors targeting anti-inflammatory T cells would be a promising therapeutic strategy in EAC.
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http://dx.doi.org/10.1007/s00262-020-02517-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7230052PMC
June 2020

RAI3 is overexpressed in gastric adenocarcinoma but unrelated to prognosis.

Int J Clin Exp Pathol 2019 1;12(2):606-612. Epub 2019 Feb 1.

General, Visceral and Thoracic Surgery Department and Clinic, University Medical Center Hamburg-Eppendorf Hamburg, Germany.

Purpose: Retinoic acid-induced gene 3 () has been associated with tumorigeneses in several cancer types. To clarify the clinical significance of RAI3 expression in premalignant and malignant gastric epithelium, RAI3 protein expression was assessed by immunohistochemistry on tissue microarrays (TMAs) containing 140 gastric dysplasia and 230 GC samples.

Findings: RAI3 protein expression was predominantly localized in the cell membrane and was detectable in low intensities in most of the benign gastric tissue samples. RAI3 expression was found in increased intensities in premalignant and malignant epithelium relative to non-malignant gastric epithelium (P < 0.0001). High RAI3 expression was found in 66.2% of interpretable gastric adenocarcinomas and was associated with advanced pathological tumor stage (P = 0.0014) and positive lymph node status (P = 0.0137) but was unrelated to overall survival of patients (P = 0.3743).

Conclusion: The deregulation of RAI3 in premalignant and gastric epithelium suggests a relevant role of RAI3 during gastric carcinogenesis. Additionally, RAI3 overexpression defines a subset of GCs with aggressive tumor features. However, since RAI3 expression was not associated with clinical outcome of patients, RAI3 cannot be considered as a prognostic biomarker in patients with GCs.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6945097PMC
February 2019

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

Clinical outcome of patients undergoing abdominoplasty after massive weight loss.

Surg Obes Relat Dis 2019 Aug 12;15(8):1362-1366. Epub 2019 Jun 12.

Department of Plastic, Reconstructive and Aesthetic Surgery, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany. Electronic address:

Background: Abdominoplasty is one of the most commonly performed surgical procedures to reshape the body contour in patients who have undergone massive weight loss.

Objectives: This study was undertaken to assess the clinical outcome, complication rates, and risk factors for complications of patients undergoing abdominoplasty after massive weight loss.

Setting: University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.

Method: Clinical outcome was retrospectively analyzed in 121 patients, who underwent abdominoplasty. The retrospective analysis included demographic data of patients, such as sex, age, body mass index (BMI), and pre-existing illnesses. Moreover, postoperative complications including seroma, hematoma, wound infection, and tissue necrosis were analyzed.

Results: In our study cohort, the median age was 43.7 years, the median weight was 94.7 kg, and the median BMI was 32.3 kg/m. The majority of included patients were women (70.3%). Death occurred in none of the patients. Among individuals, wound infection occurred in 3.3%, tissue necrosis in 1.7%, seroma in 7.4%, and hematoma in 3.3% of patients during the postoperative course. Reoperations were necessary in 2 patients (1.7%) due to postoperative bleeding and tissue necrosis of the navel. Tissue necrosis was significantly more often seen in a subset individual with type 2 diabetes (P = .006). Moreover, the rate of reoperations was significantly higher in patients with pre-existing cardiovascular illnesses compared with cardiovascular healthy patients (P = .036). Multivariate analysis analyzing risk factors for postoperative complications, including sex, age, BMI, diabetes, pulmonary disease, and cardiovascular disease, revealed strong independent relevance for type 2 diabetes (P = .024).

Conclusions: We found that abdominoplasty is a safe operative procedure. In addition, the risk for complications is significantly increased in the subgroup of diabetic patients and patients with cardiovascular diseases.
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http://dx.doi.org/10.1016/j.soard.2019.06.001DOI Listing
August 2019

Aberrant expression of Sec61α in esophageal cancers.

J Cancer Res Clin Oncol 2019 Aug 13;145(8):2039-2044. Epub 2019 Jun 13.

General, Visceral and Thoracic Surgery Department and Clinic, University Medical Center Hamburg-Eppendorf, 20251, Hamburg, Germany.

Introduction: The heterotrimeric Sec61α translocon complex is topological located in the membrane of the endoplasmic reticulum (ER) and allows protein transport and calcium across the membrane. Recently, aberrant expression of Sec proteins was linked to carcinogenesis and prognosis of patients.

Materials And Methods: Here, we analysed the role of Sec61α in esophageal cancer, and we analysed Sec61α staining on a tissue microarray containing more than 600 esophageal cancer specimens by immunohistochemistry.

Results: Sec61α staining was always strong in benign esophagus, but was only found in 5% of interpretable esophageal adenocarcinomas (EACs) and 14.5% of squamous cell carcinomas (ESCCs). Reduced Sec61α staining was not strongly linked to tumor phenotype in both subgroups of esophageal cancers and was unrelated to clinical outcome of patients (EACs: p = 0.8051 and ESCCs: p = 0.2751).

Conclusions: Thus, Sec61α measurement has not an additional prognostic benefit for the patients.
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http://dx.doi.org/10.1007/s00432-019-02955-7DOI Listing
August 2019

Cholecystokinin-8 treatment reduces acinar necrosis and edema of pigs with induced pancreatitis.

Asian J Surg 2020 Jan 3;43(1):272-277. Epub 2019 Jun 3.

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

Background: Acute pancreatitis is an inflammatory process of the pancreas and a leading cause of hospitalization amongst gastrointestinal disorders. Previously, cholecystokinin (CCK) has been described to play a role in regeneration of pancreas. The aim of this study was to analyse the function of cholecystokinin octapeptide (CCK-8) during induced pancreatitis in an animal model.

Methods: Overall acute pancreatitis was induced in 38 pigs. After the induction of acute pancreatitis, half of the animals were treated with CCK-8. Intraoperative clinical data, postoperative blood parameters, 'Porcine Well-being' (PWB) and fitness score and post-mortal histopathological data were analysed.

Results: At baseline, physiologically parameters of the pigs of both groups were comparable. No differences were observed regarding the overall survival of animals (p = 0.97). Postoperative PWB score were significantly enhanced in animals treated with CCK-8 as compared to the control group (p = 0.029). Moreover, histopathological analysis of the pancreatic tissue revealed that acinar necrosis and edema were significant reduced in the CCK-8 group in comparison to the control group (p = 0.016 and p = 0.019).

Conclusions: In conclusion, we found that CCK-8 treatment reduces acinar necrosis and edema of pancreatic tissue after induction of an acute pancreatitis in pigs.
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http://dx.doi.org/10.1016/j.asjsur.2019.05.002DOI Listing
January 2020

Critical evaluation of the DNA-methylation markers ABCG1 and SREBF1 for Type 2 diabetes stratification.

Epigenomics 2019 06 6;11(8):885-897. Epub 2019 Jun 6.

Medical Department I, Division Epigenetics & Metabolism, University of Lübeck, Lübeck, Germany.

Validation of epigenome-wide association studies is sparse. Therefore, we evaluated the methylation markers cg06500161 () and cg11024682 () as classifiers for diabetes stratification. DNA methylation was measured in blood (n = 167), liver (n = 99) and visceral adipose tissue (n = 99) of nondiabetic or Type 2 diabetic subjects by bisulfite pyrosequencing. DNA methylation at cg11024682 in blood and liver correlated with BMI. Methylation at cg06500161 was influenced by the adjacent SNP rs9982016. Insulin-resistant and sensitive subjects could be stratified by DNA methylation status in blood or visceral adipose tissue. DNA methylation at both loci in blood presents a promising approach for risk group stratification and could be valuable for personalized Type 2 diabetes risk prediction in the future.
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http://dx.doi.org/10.2217/epi-2018-0159DOI Listing
June 2019

Melatonin treatment of pigs with acute pancreatitis reduces inflammatory reaction of pancreatic tissue and enhances fitness score of pigs: experimental research.

World J Emerg Surg 2019 11;14:18. Epub 2019 Apr 11.

1Department of General, Visceral and Thoracic Surgery, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.

Background: Severe acute pancreatitis is associated with high morbidity and mortality. Melatonin is known as the activator of antioxidant enzymes. The main purpose of this study was to evaluate the clinical effect of melatonin treatment in a pig model with induced acute pancreatitis.

Methods: In this study, acute pancreatitis was induced in 38 German domestic pigs (German Hybrid). After induction of acute pancreatitis, 18 animals were treated with melatonin. Intraoperative clinical data, postoperative blood parameters, fitness, and Porcine Well-being (PWB) score, and post-mortal histopathological data were analyzed in both study groups.

Results: The matching procedure created two groups (melatonin group and control group) which were very similar. The fitness and PWB score were postoperative significantly enhanced in the melatonin group as compared to the control group ( = 0.005 and  = 0.003). Additionally, histological analysis revealed that acinar necrosis, fat tissue necrosis, and edema were significantly reduced in the melatonin group as compared to the non-melatonin group ( = 0.025,  = 0.003, and  = 0.028).

Conclusions: Pigs, which were treated with melatonin, were characterized by higher fitness and PWB scores than those of the control group. Moreover, melatonin treatment reduces the acinar necrosis, fat tissue necrosis, and edema of pancreatic tissue. Thus, melatonin might be a useful therapeutic option in severe acute pancreatitis.
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http://dx.doi.org/10.1186/s13017-019-0237-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6458612PMC
July 2019

Prevalence and clinical significance of RBM3 immunostaining in non-small cell lung cancers.

J Cancer Res Clin Oncol 2019 Apr 13;145(4):873-879. Epub 2019 Feb 13.

General-, Visceral and Thoracic Surgery Department and Clinic, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Introduction: Aberrant expression of RNA-binding motif protein 3 (RBM3) has been suggested as a prognostic biomarker in several malignancies.

Materials And Methods: This study was performed to analyse the prevalence and clinical significance of RBM3 immunostaining in non-small cell lung cancers (NSCLCs). Therefore, we took advantage of our tissue microarray (TMA) containing more than 600 NSCLC specimens.

Results: While nuclear RBM3 staining was always high in normal lung tissue, high RBM3 staining was only seen in 77.1% of 467 interpretable non-metastatic NSCLCs. Reduced RBM3 staining was significantly associated with advanced pathological tumor stage (pT) in NSCLCs (p = 0.0031). Subset analysis revealed that the association between reduced RBM3 staining and advanced pT stage was largely driven by the histological subgroup of lung adenocarcinoma (LUACs) (p = 0.0036). In addition, reduced RBM3 expression predicted shortened survival in LUAC patients (p = 0.0225).

Conclusions: In summary, our study shows that loss of RBM3 expression predicts worse clinical outcome in LUAC patients.
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http://dx.doi.org/10.1007/s00432-019-02850-1DOI Listing
April 2019

High levels of RAI3 expression is linked to shortened survival in esophageal cancer patients.

Exp Mol Pathol 2019 04 29;107:51-56. Epub 2019 Jan 29.

General, Visceral and Thoracic Surgery Department and Clinic, University Medical Center Hamburg-Eppendorf, Germany. Electronic address:

Expression of the retinoic acid-induced protein 3 (RAI3) has been suggested to predict clinical outcome in a variety of malignancies. However, its role in esophageal cancers remains unclear. Immunohistochemical RAI3 staining was analyzed on tissue microarrays containing 359 esophageal adenocarcinomas (EAC) and 254 esophageal squamous cell carcinomas (ESCC). RAI3 immunostaining was typically absent or weakly detectable in the membranes in benign esophageal tissues. RAI3 staining was higher in malignant than in benign esophagus epithelium. High-levels of RAI3 staining were found in 79.2% of interpretable EACs and 55.9% of ESCCs. In EACs, strong RAI3 staining was associated with advanced pathological tumor stage (p < .0001), high UICC stage (p < .0001), high tumor grade (p = .0133), and positive lymph nodal status (p = .0002). Additionally, high RAI3 staining predicted shortened overall survival of EAC and ESCC patients (p = .0298 and p = .0227). RAI3 overexpression is associated with poor prognosis in esophageal cancers. We propose that RAI3 overexpression might play a biologically relevant role of RAI3 in esophageal cancers.
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http://dx.doi.org/10.1016/j.yexmp.2019.01.013DOI Listing
April 2019

Reduced expression of thyroid hormone receptor β in human nonalcoholic steatohepatitis.

Endocr Connect 2018 Dec;7(12):1448-1456

Epigenetics & Metabolism, Medical Department I, University of Lübeck, Lübeck, Germany.

Hepatic thyroid hormone signaling has an important role in the development and progression of nonalcoholic steatohepatitis (NASH). While the systemic levels of thyroid hormone might remain stable, there is evidence that the intracellular signaling machinery consisting of transporters, deiodinases and receptors could be altered in NASH. However, clinical material from human liver biopsies of individuals with NASH has not been studied to date. In a cross-sectional study, we analyzed 85 liver biopsies from patients with different stages of NASH that underwent bariatric surgery. Using qPCR, we analyzed gene expression of thyroid hormone transporters NTCP (SLC10A1), MCT8 (SLC16A2) and OATP1C1 (SLCO1C1), thyroid hormone receptor α and β (THRA and THRB) and deiodinase type I, II and III (DIO1, DIO2, DIO3). The expression was correlated with serum TSH, triglyceride, HbA1c and NASH score and corrected for age or gender if required. While DIO2, DIO3 and SLCO1C1 were not expressed in human liver, we observed a significant negative correlation of THRB and DIO1 with age, and SLC16A2 with gender. THRB expression was also negatively associated with serum triglyceride levels and HbA1c. More importantly, its expression was inversely correlated with NASH score and further declined with age. Our data provide unique insight into the mRNA expression of thyroid hormone transporters, deiodinases and receptors in the human liver. The findings allow important conclusions on the intrahepatic mechanisms governing thyroid hormone action, indicating a possible tissue resistance to the circulating hormone in NASH, which becomes more prominent in advanced age.
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http://dx.doi.org/10.1530/EC-18-0499DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6300861PMC
December 2018

Decomposition of dissolved organic contaminants by combining a boron-doped diamond electrode, zero-valent iron and ultraviolet radiation.

Chemosphere 2019 Feb 5;217:897-904. Epub 2018 Nov 5.

ESW Consulting Wruss, Rosasgasse 25-27, 1120, Vienna, Austria. Electronic address:

This study presents the results of a research project dealing with the degradation of dissolved tetrachloroethene, MTBE and clopyralid by using a boron-doped diamond electrode, zero-valent iron in a fluidized bed reactor and ultraviolet radiation. These treatment methods were tested alone, in any combination of two as well as in combination of all three of them to identify emerging synergy effects. Additionally, the influence of adding HO or HO + HSO is investigated. The experiments revealed that the treatment methods alone were able to decrease the organic contaminant concentrations, yet, the decomposition rate was not very sufficient. Applying the BDD yielded the highest decomposition rates, however, this degradation was accompanied by metabolite production. By combining two methods and adding HO, the decomposition was enhanced significantly for any combination. These removal rates were further increased by using the combination of the three treatment methods and adding HO or HO + HSO. These high removal rates were not achieved by solely using the combination of the three methods without further addition of chemicals. This research demonstrates the potential, but also the limitations of the investigated system.
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http://dx.doi.org/10.1016/j.chemosphere.2018.11.043DOI Listing
February 2019

Mentorship Programs in Bariatric Surgery Reduce Perioperative Complication Rate at Equal Short-Term Outcome-Results from the OPTIMIZE Trial.

Obes Surg 2019 01;29(1):127-136

Department of General-, Visceral- and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany.

Objectives: The aim of this study was to determine the efficacy of coaching on outcome in low volume centers of excellence and to evaluate the influence of mentorship programs on the center development.

Background: The number of bariatric procedures has increased steadily in the last years. Providing nationwide bariatric care on a high professional level needs structures to train and guide upcoming centers and ensure high quality in patient care.

Methods: A prospective multicentered, observational study including laparoscopic sleeve gastrectomies (SG) and Roux-en-Y gastric bypass (RYGB) procedures was performed. Twelve emerging bariatric centers were coached by five experienced bariatric centers. Surgeons of the mentor centers gave guidance on pre- and postsurgical management of their patients including complications and proctored the first interventions. The results were compared regarding operative outcomes, percentage of excess weight loss, complications, and resolution of comorbidities.

Results: A total of 214 of 293 patients (73.0%) completed the study. The most frequently reported complications were wound infection (4.4%), disorder of emptying stomach/new reflux (2.4%), anastomotic leaks, intra-abdominal secondary hemorrhage, and dumping syndrome (2.0% each). The mortality rate was zero. We found no difference in overall complication rates or resolution of obesity-related comorbidities when comparing experienced surgeons with less experienced surgeons.

Conclusions: Our results suggest that under the conditions of the practices of this study, coaching and mentoring were associated with comparable outcomes both in experienced and emerging centers. In addition, mentorship programs ensure equal outcome quality in terms of improvement of obesity-associated comorbidities.

Trial Registration: NCT Number: NCT01754194 .
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http://dx.doi.org/10.1007/s11695-018-3495-2DOI Listing
January 2019

Perioperative Short-Term Outcome in Super-Super-Obese Patients Undergoing Bariatric Surgery.

Obes Surg 2018 07;28(7):1895-1901

Department General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany.

Background: Prevalence of obesity is increasing with a pandemic magnitude worldwide. Incidence of super-super-obesity (> 60 kg/m) is expanding by the same means. While bariatric surgery is the only approach with proven long-term results, surgical outcome in super-super-obesity is still discussed controversially.

Objective: This retrospective study examined bariatric surgery patients' short-term outcome in relation to their degree of obesity.

Setting: Data collection was performed in a German university medical center between March 2010 and November 2013.

Methods: This study analyzes a cohort of 715 patients in a single institution. Patients were subdivided into three groups, obese (≤ 49.9 kg/m), super-obese (≥ 50 kg/m), and super-super-obese (≥ 60 kg/m), and evaluated regarding perioperative outcome.

Results: Three hundred eighty-one patients were included into obese (O); 225 patients, into super-obese (SO); and 109 patients, into super-super-obese (SSO) cohort. There were no significant differences regarding patient characteristics including quantity of comorbidities and perioperative outcome. BMI was significantly lower in patients with complications, compared to patients without complications (p < 0.05), whereas patients' age was significantly higher (p < 0.05) in complication cohort. One SSO patient died of a septic multiorgan failure. Thus, the 30-day overall mortality was 0.14%. The BMI showed an inverse correlation to the patients' age at surgery (p < 0.05).

Conclusion: Super-super-obesity should not be considered as a limiting factor for bariatric surgery outcome; however, the patients' age, surgeries prior to the bariatric procedure, and comorbidities must be considered prior to bariatric surgical treatment.
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http://dx.doi.org/10.1007/s11695-018-3118-yDOI Listing
July 2018

Development of Obesity-Associated Comorbidities Post Bariatric Surgery with a Special Focus on Diabetes Remission and Short-Term Relapse.

Exp Clin Endocrinol Diabetes 2018 Sep 8;126(9):577-583. Epub 2017 Nov 8.

Department for Endocrinology and Diabetology, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany.

Purpose: The purpose of this study is to study a heterogeneous group of obese patients undergoing Bariatric surgery(BS) and its impact on glycemic control. Secondary endpoints include changes in lipid profile and albuminuria. BS has shown to effectively reduce body-weight. However, the impact on obesity-related comorbidities varies strongly between individuals. Especially postoperative short- and long-term improvement of Diabetes is an active area of investigation.

Methods: We conducted a retrospective analysis from baseline to 24 months post bariatric surgery in our interdisciplinary obesity outpatient-clinic. Follow-up data was collected from 215 patients who had undergone either Roux-en-Y gastric bypass or Sleeve Gastrectomy. The prevalence of and changes in the major obesity-related comorbidities and concurrent medication were assessed.

Results: Standard parameters of diabetic control showed a U-shaped curve with initial improvement after six months, but with a gradual worsening after the first year of follow-up. Weight loss resulted in dose reduction of oral antidiabetic medication and insulin in 85% and 100% of patients, respectively. With weight loss, a significant improvement in lipid profile one year after surgery was seen. Subgroup analysis demonstrated gender- and age-dependent differences in overall benefit.

Conclusions: Current data on diabetes remission might be too optimistic and close follow-up should be provided to prevent gradual worsening of glucose metabolism after BS.
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http://dx.doi.org/10.1055/s-0043-119985DOI Listing
September 2018

Cost-utility analysis of bariatric surgery compared with conventional medical management in Germany: a decision analytic modeling.

BMC Surg 2017 Aug 3;17(1):87. Epub 2017 Aug 3.

University Medical Center Hamburg, Hamburg, Germany.

Background: The objective was to evaluate cost-utility of bariatric surgery in Germany for a lifetime and 10-year horizon from a health care payer perspective.

Methods: State-transition Markov model provided absolute and incremental clinical and monetary results. In the model, obese patients could undergo surgery, develop post-surgery complications, experience diabetes type II, cardiovascular diseases or die. German Quality Assurance in Bariatric Surgery Registry and literature sources provided data on clinical effectiveness and safety. The model considered three types of surgeries: gastric bypass, sleeve gastrectomy, and adjustable gastric banding. The model was extensively validated, and deterministic and probabilistic sensitivity analyses were performed to evaluate uncertainty. Cost data were obtained from German sources and presented in 2012 euros (€).

Results: Over 10 years, bariatric surgery led to the incremental cost of €2909, generated additional 0.03 years of life and 1.2 quality-adjusted life years (QALYs). Bariatric surgery was cost-effective at 10 years with an incremental cost-effectiveness ratio of €2457 per QALY. Over a lifetime, surgery led to savings of €8522 and generated an increment of 0.7 years of life or 3.2 QALYs. The analysis also depicted an association between surgery and a reduction of obesity-related adverse events (diabetes, cardiovascular disorders). Delaying surgery for up to 3 years, resulted in a reduction of life years and QALYs gained, in addition to a moderate reduction in associated healthcare costs.

Conclusions: Bariatric surgery is cost-effective at 10 years post-surgery and may result in a substantial reduction in the financial burden on the healthcare system over the lifetime of the treated individuals. It is also observed that delays in the provision of surgery may lead to a significant loss of clinical benefits.
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http://dx.doi.org/10.1186/s12893-017-0284-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5543597PMC
August 2017

Upper Gastrointestinal Endoscopy prior to Bariatric Surgery-Mandatory or Expendable? An Analysis of 801 Cases.

Obes Surg 2017 08;27(8):1938-1943

Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany.

Background: Upper gastrointestinal pathologies are common in bariatric patients. Preoperative esophagogastroduodenal endoscopy (EGD) should detect and treat pathologies that might alter the type of bariatric surgery. However, clinical consequences of these findings are often insignificant. The aim of this study was to assess the influence of preoperative endoscopy in our cohort and its clinical consequences.

Methods: We conducted a retrospective analysis of endoscopic findings in patients under evaluation for bariatric surgery. Endoscopic findings were compared to preoperative risk factors as well as postoperative complications, and its clinical consequences were analyzed.

Results: Data was available for 801 patients. Abnormal endoscopic findings were found in 65.7% of all patients. The most common conditions were gastritis (32.1%) and gastroesophageal reflux (24.8%). Malignancies were observed in 0.5% of all patients. We observed early-stage adenocarcinoma of the esophagus in two patients through our routine preoperative evaluation. Helicobacter pylori infections were detected in preoperative biopsies in only 3.7% of all patients. Patients who reported reflux symptoms had a higher rate of pathological EGDs (74.2 vs. 64.9%, p .019). We did not find any other risk factors for a pathological endoscopy. The postoperative complication rate was 11.2%. Leakage rate was 1.1%. Mortality rate was 0.4%. We did not find any correlation between the incidence of postoperative complications and preoperative endoscopic findings.

Conclusions: Relevant findings in routine preoperative endoscopy are rare but have significant influence on decision-making in bariatric patients and should be assessed as a necessary diagnostic tool.
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http://dx.doi.org/10.1007/s11695-017-2622-9DOI Listing
August 2017

Anesthetic considerations for patients with esophageal achalasia undergoing peroral endoscopic myotomy: a retrospective case series review.

Can J Anaesth 2017 May 23;64(5):480-488. Epub 2017 Jan 23.

Department of Anesthesiology, Center of Anesthesiology and Intensive Care Medicine, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20251, Hamburg, Germany.

Purpose: Peroral endoscopic myotomy (POEM) is a novel technique for treating esophageal achalasia. During POEM, carbon dioxide (CO) is insufflated to aid surgical dissection, but it may inadvertently track into surrounding tissues, causing systemic CO uptake and tension capnoperitoneum. This in turn may affect cardiorespiratory function. This study quantified these cardiorespiratory effects and treatment by hyperventilation and percutaneous abdominal needle decompression (PND).

Methods: One hundred and seventy-three consecutive patients who underwent POEM were included in this four-year retrospective study. Procedure-related changes in peak inspiratory pressure (p), end-tidal CO levels (etCO), minute ventilation (MV), mean arterial pressure (MAP), and heart rate (HR) were analyzed. We also quantified the impact of PND on these cardiorespiratory parameters.

Results: During the endoscopic procedure, cardiorespiratory parameters increased from baseline: p 15.1 (4.5) vs 19.8 (4.7) cm HO; etCO 4.5 (0.4) vs 5.5 (0.9) kPa [34.0 (2.9) vs 41.6 (6.9) mmHg]; MAP 73.9 (9.7) vs 99.3 (15.2) mmHg; HR 67.6 (12.4) vs 85.3 (16.4) min (P < 0.001 for each). Hyperventilation [MV 5.9 (1.2) vs 9.0 (1.8) L·min, P < 0.001] was applied to counteract iatrogenic hypercapnia. Individuals with tension capnoperitoneum treated with PND (n = 55) had higher peak p values [22.8 (5.7) vs 18.4 (3.3) cm HO, P < 0.001] than patients who did not require PND. After PND, p [22.8 (5.7) vs 19.9 (4.3) cm HO, P = 0.045] and MAP [98.2 (16.3) vs 88.6 (11.8) mmHg, P = 0.013] decreased. Adverse events included pneumothorax (n = 1), transient myocardial ischemia (n = 1), and subcutaneous emphysema (n = 49). The latter precluded immediate extubation in eight cases. Postanesthesia care unit (PACU) stay was longer in individuals with subcutaneous emphysema than in those without [74.9 min (34.5) vs 61.5 (26.8 min), P = 0.007].

Conclusion: Carbon dioxide insufflation during POEM produces systemic CO uptake and increased intra-abdominal pressure. Changes in cardiorespiratory parameters include increased p, etCO, MAP, and HR. Hyperventilation and PND help mitigate some of these changes. Subcutaneous emphysema is common and may delay extubation and prolong PACU stay.
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http://dx.doi.org/10.1007/s12630-017-0820-5DOI Listing
May 2017

Early adverse events of per-oral endoscopic myotomy.

Gastrointest Endosc 2017 Apr 5;85(4):708-718.e2. Epub 2016 Sep 5.

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

Background And Aims: The recently developed technique of per-oral endoscopic myotomy (POEM) has been shown to be effective for the therapy of esophageal motility disorders. Limited information is available about POEM adverse events (AEs).

Methods: POEM was performed on 241 patients (58% male; mean age, 47.4 ± 16.4 years) under general anesthesia over 61 months. The main outcome was the rate of intra- and post-procedural AEs. Post-procedural checks comprised clinical and laboratory examinations and endoscopy, with further follow-ups performed at 3, 6, and 12 months.

Results: Of the 241 procedures, 238 were successfully completed (mean procedure time, 100.2 ± 39.5 min). Reasons for abortion were excessive submucosal fibrosis preventing submucosal tunneling. Three patients had severe procedural-related AEs (SAE rate, 1.2%); 1 case of pneumothorax required intra-procedural drainage, and 2 patients had delayed SAEs (1 ischemic gastric cardia perforation and 1 hemothorax, both leading to surgery). The overall rate of minor AEs was 31.1%, mainly prolonged intra-procedural bleeding (>15 min hemostasis) and defects of the mucosa overlying the tunnel; none led to clinically relevant signs or symptoms. Patients experiencing any AE had a significantly prolonged hospital stay (P = .037) and a trend toward prolonged procedure time (P = .094). Neck/upper thoracic emphysema and free abdominal air were noted in 31.5% and 35.7%, respectively (95.3% drained), but without relevant sequelae.

Conclusions: POEM has a low rate of SAEs; minor AEs are more frequent but lack a consistent definition. Therefore, based on our experience and literature analysis, we suggest a classification of AEs for POEM. (Clinical trials registration number: NCT01405417.).
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http://dx.doi.org/10.1016/j.gie.2016.08.033DOI Listing
April 2017