Publications by authors named "Jakob Izbicki"

399 Publications

[Erratum to: The paraplegic patient. Characteristics of diagnostics and treatment in visceral surgery].

Chirurg 2021 Apr 1. Epub 2021 Apr 1.

Abteilung für Allgemein und Viszeralchirurgie, BG Klinikum Hamburg, Hamburg, Deutschland.

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http://dx.doi.org/10.1007/s00104-021-01392-yDOI Listing
April 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

[The paraplegic patient-Characteristics of diagnostics and treatment in visceral surgery].

Chirurg 2021 Feb 25. Epub 2021 Feb 25.

Abteilung für Allgemein und Viszeralchirurgie, BG Klinikum Hamburg, Hamburg, Deutschland.

Background: Patients with paraplegia develop syndrome-specific complications relevant to visceral surgery, which occur in the context of the acute spinal shock or as a consequence of the progressive neurogenic bowel dysfunction (NBD) with the formation of an elongated colon and/or megacolon. Moreover, acute abdominal emergencies, such as acute appendicitis, cholecystitis, diverticulitis and ileus images, pose particular challenges for the clinician when the clinical signs are atypical or even absent. The expansion of indications for obesity surgery to include patients with a paraplegic syndrome, whose independence and quality of life can be impaired due to the restricted mobility, especially by obesity, is becoming increasingly more important.

Objective: This article provides an overview of the special requirements and aspects in the treatment of this special patient collective and to show the evidence of paraplegia-specific visceral surgery treatment.

Material And Methods: Targeted literature search in Medline and Cochrane library (German and English, 1985-2020).

Results And Conclusion: The clinical treatment of paraplegic patients requires in-depth knowledge of the pathophysiological changes at the different height of the paraplegia (upper versus lower motor neuron) and the phase of the disease (spinal shock versus long-term course). Missing or atypical clinical symptoms of acute diseases delay a quick diagnosis and make early diagnosis essential. The evidence for surgical treatment of the acute and chronic consequences of NBD is based on small retrospective series and case reports, as is that for special indications such as obesity surgery.
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http://dx.doi.org/10.1007/s00104-021-01364-2DOI Listing
February 2021

Reduced anoctamin 7 (ANO7) expression is a strong and independent predictor of poor prognosis in prostate cancer.

Cancer Biol Med 2021 Feb;18(1):245-255

Department of Urology, University Medical Center Hamburg-Eppendorf, Hamburg 20246, Germany.

Objective: Anoctamin 7 (ANO7) is a calcium-dependent chloride ion channel protein. Its expression is restricted to prostate epithelial cells. The exact function is unknown. This study aimed to analyze ANO7 expression and its clinical significance in prostate cancer (PCa).

Methods: ANO7 expression was assessed by immunohistochemistry in 17,747 clinical PCa specimens.

Results: ANO7 was strongly expressed in normal prostate glandular cells but often less abundant in cancer cells. ANO7 staining was interpretable in 13,594 cancer tissues and considered strong in 34.4%, moderate in 48.7%, weak in 9.3%, and negative in 7.6%. Reduced staining was tightly linked to adverse tumor features [high classical and quantitative Gleason grade, lymph node metastasis, advanced tumor stage, high Ki67 labeling index, positive surgical margin, and early biochemical recurrence ( < 0.0001 each)]. The univariate Cox hazard ratio for prostate-specific antigen (PSA) recurrence after prostatectomy in patients with negative strong ANO7 expression was 2.98 (95% confidence interval 2.61-3.38). The prognostic impact was independent of established pre- or postoperatively available parameters ( < 0.0001). Analysis of annotated molecular data showed that low ANO7 expression was linked to G fusions ( < 0.0001), elevated androgen receptor expression ( < 0.0001), as well as presence of 9 of 11 chromosomal deletions ( < 0.05 each). A particularly strong association of low ANO7 expression with phosphatase and tensin homolog (PTEN) deletion may indicate a functional relationship with the PTEN/AKT pathway.

Conclusions: These data identify reduced ANO7 protein expression as a strong and independent predictor of poor prognosis in PCa. ANO7 measurement, either alone or in combination, might provide clinically useful prognostic information in PCa.
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http://dx.doi.org/10.20892/j.issn.2095-3941.2019.0324DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7877177PMC
February 2021

Genome-wide scan of long noncoding RNA single nucleotide polymorphisms and pancreatic cancer susceptibility.

Int J Cancer 2021 Jun 3;148(11):2779-2788. Epub 2021 Feb 3.

Department of Biology, University of Pisa, Pisa, Italy.

Pancreatic ductal adenocarcinoma (PDAC) is projected to become the second cancer-related cause of death by 2030. Identifying novel risk factors, including genetic risk loci, could be instrumental in risk stratification and implementation of prevention strategies. Long noncoding RNAs (lncRNAs) are involved in regulation of key biological processes, and the possible role of their genetic variability has been unexplored so far. Combining genome wide association studies and functional data, we investigated the genetic variability in all lncRNAs. We analyzed 9893 PDAC cases and 9969 controls and identified a genome-wide significant association between the rs7046076 SNP and risk of developing PDAC (P = 9.73 × 10 ). This SNP is located in the NONHSAG053086.2 (lnc-SMC2-1) gene and the risk allele is predicted to disrupt the binding of the lncRNA with the micro-RNA (miRNA) hsa-mir-1256 that regulates several genes involved in cell cycle, such as CDKN2B. The CDKN2B region is pleiotropic and its genetic variants have been associated with several human diseases, possibly though an imperfect interaction between lncRNA and miRNA. We present a novel PDAC risk locus, supported by a genome-wide statistical significance and a plausible biological mechanism.
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http://dx.doi.org/10.1002/ijc.33475DOI Listing
June 2021

as an important differential diagnosis in patients suffering from stridor following thyroidectomy.

Clin Case Rep 2021 Jan 19;9(1):470-472. Epub 2020 Nov 19.

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

It is essential to consider hypocalcemia as a cause of stridor, especially following postoperative thyroidectomy, as hypocalcemia secondary to hypoparathyroidism is an important differential diagnosis. Advances in intraoperative technology to optimize the vascularization of the parathyroid glands can help to predict and prevent patients from a postoperative hypoparathyroidism.
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http://dx.doi.org/10.1002/ccr3.3559DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7813116PMC
January 2021

Acute Mesenteric Infarction: The Chameleon of Acute Abdomen Evaluating the Quality of the Diagnostic Parameters in Acute Mesenteric Ischemia.

Dig Surg 2021 27;38(2):149-157. Epub 2021 Jan 27.

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

Introduction/objective: Acute mesenteric ischemia (AMI) is difficult to diagnose. Since the established parameters have low sensitivity and specificity, the aim of this study is to analyze the diagnostic quality of the established parameters of AMI.

Methods: All patients that underwent emergency surgery due to suspected diagnosis of mesenteric ischemia at the University Medical Center Hamburg-Eppendorf between 2008 and 2014 were evaluated. Overall, 275 patients were enrolled and pre-, intra- and postoperative data were evaluated.

Results: In 200 patients, a mesenteric ischemia was confirmed intraoperatively, and 75 patients had no ischemia. Comparing these groups, the rate of patients with pH < 7.2 (25 vs. 12%; p = 0.021) and elevated mean CRP level (175 ± 117 mg/L vs. 139 ± 104 mg/L; p = 0.019) was significantly higher in ischemic patients. There was no significant difference in the level of preoperative lactate. Concerning abdominal CT scan, a sensitivity and specificity of 61 and 68%, respectively, was found.

Conclusion: New diagnostic parameters are needed. So far, explorative laparotomy is the only reliable diagnostic method to detect mesenteric infarction.
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http://dx.doi.org/10.1159/000512779DOI Listing
January 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

Elevated MUC5AC expression is associated with mismatch repair deficiency and proximal tumor location but not with cancer progression in colon cancer.

Med Mol Morphol 2020 Dec 29. Epub 2020 Dec 29.

Institute of Pathology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany.

Mucin 5AC (MUC5AC) is a secreted gel-forming mucin expressed by several epithelia. In the colon, MUC5AC is expressed in scattered normal epithelial cells but can be abundant in colorectal cancers. To clarify the relationship of MUC5AC expression with parameters of tumor aggressiveness and mismatch repair deficiency (dMMR) in colorectal cancer, a tissue microarray containing 1812 colorectal cancers was analyzed by immunohistochemistry. MUC5AC expression was found in 261 (15.7%) of 1,667 analyzable colorectal cancers. MUC5AC expression strongly depended on the tumor location and gradually decreased from proximal (27.4% of cecum cancers) to distal (10.6% of rectal cancers; p < 0.0001). MUC5AC expression was also strongly linked to dMMR. dMMR was found in 21.3% of 169 cancers with MUC5AC positivity but in only 4.6% of 1051 cancers without detectable MUC5AC expression (p < 0.0001). A multivariate analysis showed that dMMR status and tumor localization predicted MUC5AC expression independently (p < 0.0001 each). MUC5AC expression was unrelated to pT and pN status. This also applied to the subgroups of 1136 proficient MMR (pMMR) and of 84 dMMR cancers. The results of our study show a strong association of MUC5AC expression with proximal and dMMR colorectal cancers. However, MUC5AC expression is unrelated to colon cancer aggressiveness.
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http://dx.doi.org/10.1007/s00795-020-00274-2DOI Listing
December 2020

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

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

Antibiotic sensitivity in correlation to the origin of secondary peritonitis: a single center analysis.

Sci Rep 2020 10 29;10(1):18588. Epub 2020 Oct 29.

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

Despite improvements in diagnosis, intensive-care medicine and surgical technique, the mortality of patients with secondary peritonitis is still high. Early and aggressive empiric antibiotic treatment has strong impact on the outcome. This retrospective study investigates bacterial and fungal pathogens and their antibiotic sensitivity in patients with secondary peritonitis. All patients that underwent emergency laparotomy due to secondary peritonitis at the Department of Surgery, University Medical Center Hamburg-Eppendorf between 2005 and 2015 were reviewed and overall 414 patients were included. We correlated the intra-abdominal localization of the organ perforation with intraoperative microbiological findings and corresponding sensitivities to relevant antibiotics. Overall, the most common findings were Escherichia coli (39%) and other Enterobacterica (24%). Depending on the location of the perforation, Cefuroxime/Metronidazole and Cefutaxime/Metronidazole were effective (based on in vitro susceptibility testing) in only 55-73% of the patients, while Meropenem/Vancomycin was able to control the peritonitis in more than 98% of the patients; independent of the location. Besides early source control, appropriate empiric treatment plays a pivotal role in treatment of secondary peritonitis. We are able to show that the frequently used combinations of second or third generation Cephalosporins with Metronidazole are not always sufficient, which is due to the biological resistance of the bacteria. Further clinical studies are needed to determine whether calculated use of broad-spectrum antibiotics with a sensitivity rate > 99%, such as Carbapenem plus Vancomycin, can improve overall survival rates in critically ill patients with secondary peritonitis.
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http://dx.doi.org/10.1038/s41598-020-73356-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7596236PMC
October 2020

Differential regulation of extracellular matrix proteins in three recurrent liver metastases of a single patient with colorectal cancer.

Clin Exp Metastasis 2020 Dec 24;37(6):649-656. Epub 2020 Oct 24.

Institute of Biochemistry and Signal Transduction, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246, Hamburg, Germany.

Colorectal cancer (CRC) patients suffer from the second highest mortality among all cancer entities. In half of all CRC patients, colorectal cancer liver metastases (CRLM) can be observed. Metastatic colorectal cancer is associated with poor overall survival and limited treatment options. Even after successful surgical resection of the primary tumor, metachronous liver metastases occur in one out of eight cases. The only available curative intended treatment is hepatic resection, but metachronous CRLM frequently recur after approximately 1 year. In this study, we performed a proteome analysis of three recurrent liver metastases of a single CRC patient by mass spectrometry. Despite surgical resection of the primary CRC and adjuvant chemotherapy plus cetuximab treatment, the patient developed three metachronous CRLM which occurred consecutively after 9, 21 and 31 months. We identified a set of 1132 proteins expressed in the three metachronous CRLM, of which 481 were differentially regulated, including 81 proteins that were associated with the extracellular matrix (ECM). 56 ECM associated proteins were identified as upregulated in the third metastasis, 26 (46%) of which were previously described as negative prognostic markers in CRC, including tenascin C, nidogen 1, fibulin 1 and vitronectin. These data may reflect an ascending trend of malignancy from the first to the third metachronous colorectal cancer liver metastasis. Additionally, the results indicate different ECM phenotypes for recurrent metachronous metastasis, associated with different grades of malignancy and highlights the importance of individual analysis of molecular features in different, consecutive metastatic events in a single patient.
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http://dx.doi.org/10.1007/s10585-020-10058-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7666585PMC
December 2020

Perforation of the ascending colon during implantation of an indwelling peritoneal catheter: a case report.

BMC Gastroenterol 2020 Oct 16;20(1):345. Epub 2020 Oct 16.

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

Background: Tunneled peritoneal drainage catheters are described as an effective and relatively safe method in the management of malignant and non-malignant refractory ascites. Therapeutic advantages, linked to their use, are self-management of ascites and palliative care at home. Complications occur rarely. We describe an ascending colon perforation after implantation of a peritoneal drainage in a patient with refractory ascites due to liver cirrhosis.

Case Presentation: The 68-year-old male was admitted to the intensive care unit due to severe community acquired pneumonia. The ascites drainage was inserted in order to reduce the intra-abdominal pressure and enable appropriate ventilation. A few hours later, bowel content could be detected in the tube and an abdominal computed tomography confirmed the intestinal perforation. Notably, there was no pneumoperitoneum and peritonitis had not yet set in. The catheter was removed during an emergency laparotomy and sutured closure of both perforation sites was performed.

Conclusion: Patients with septated ascites and intraperitoneal adhesions are at potential higher risk of bowel perforation during implantation of an indwelling peritoneal catheter. A mini-laparotomy is, therefore, necessary in order to ensure safe implantation and positioning of the catheter in those cases.
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http://dx.doi.org/10.1186/s12876-020-01489-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7566115PMC
October 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

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

A single-center experience: management of patients with thymic epithelial tumors.

World J Surg Oncol 2020 Aug 13;18(1):202. Epub 2020 Aug 13.

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

Background: Thymic epithelial tumors are rare neoplasias. There are no internationally accepted standards to treat this complex oncological disease. The studies on which our knowledge is based frequently have methodological weaknesses. If the tumor is resectable, complete surgical excision is currently the first-line therapy. Thymic epithelial tumors respond to radiation. The therapeutic benefit of adjuvant radiotherapy depends on tumor stage. To validate and improve treatment, we share our current experiences with clinical management and surgical intervention.

Methods: This single-center retrospective study included 40 patients with primarily resectable thymic epithelial tumors who underwent resection with curative intent. The survival data was collected and presented according to Kaplan-Meier. Single- and multiple predictor survival analyses were carried out using the log-rank test and Cox proportional hazards model.

Results: Single-predictor survival analysis showed survival to be dependent on the Masaoka-Koga classification, WHO histological classification, resection status, surgical technique, and Clavien-Dindo grade for postoperative complications. Multiple predictor analysis confirms that the Masaoka-Koga stage (HR = 4.876, P = 0.032) and Clavien-Dindo grade (HR = 4.904, P = 0.011) are independent prognostic factors for survival.

Conclusion: In addition to the Masaoka stage, the occurrence of severe postoperative complications represents an independent prognostic factor. Given the tumor's sensitivity to radiation, the use of neoadjuvant radiotherapy can be considered to downstage Masaoka-Koga stages III and higher, thus reducing surgical risks. Further prospective multicenter studies are urgently needed.
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http://dx.doi.org/10.1186/s12957-020-01988-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7427055PMC
August 2020

Prognostic value of positive histological margins in patients with pancreatic head ductal adenocarcinoma and lymph node involvement: an international multicentric study.

HPB (Oxford) 2021 Mar 8;23(3):379-386. Epub 2020 Aug 8.

Department of Visceral Surgery, Lausanne University Hospital CHUV, Lausanne, Switzerland.

Background: Resection margin status and lymph node (LN) involvement are known prognostic factors for patients who undergo pancreatoduodenectomy for pancreatic ductal adenocarcinoma (PDAC). This study aimed to compare overall survival (OS) and disease-free survival (DFS) by resection margin status in patients with PDAC and LN involvement.

Methods: A retrospective international multicentric study was performed including four Western centers. Multivariable Cox analysis was performed to identify prognostic factors of OS and DFS. Median OS and DFS were calculated using Kaplan-Meier curves and compared using log-rank tests.

Results: A cohort of 814 PDAC patients with pancreatoduodenectomy were analyzed. A total of 651 patients had LN involvement (80%). On multivariable analysis R1 resection was not an independent factor of worse OS and DFS in patients with LN involvement (HR 1.1, p = 0.565; HR 1.2, p = 0.174). Only tumor size, grade, and adjuvant chemotherapy were associated with OS and DFS. Median OS and DFS were similar between patients with R0 and R1 resections (23 vs. 20 months, p = 0.196; 15 vs. 14 months, p = 0.080).

Conclusion: Resection status was not identified as predictor of OS or DFS in PDAC patients with LN involvement. Extensive surgery to achieve R0 resection in such patients might not influence the disease course.
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http://dx.doi.org/10.1016/j.hpb.2020.07.008DOI Listing
March 2021

Personalised haemodynamic management targeting baseline cardiac index in high-risk patients undergoing major abdominal surgery: a randomised single-centre clinical trial.

Br J Anaesth 2020 08;125(2):122-132

Department of Anesthesiology, Center of Anesthesiology and Intensive Care Medicine; Outcomes Research Consortium, Cleveland, OH, USA.

Background: Despite several clinical trials on haemodynamic therapy, the optimal intraoperative haemodynamic management for high-risk patients undergoing major abdominal surgery remains unclear. We tested the hypothesis that personalised haemodynamic management targeting each individual's baseline cardiac index at rest reduces postoperative morbidity.

Methods: In this single-centre trial, 188 high-risk patients undergoing major abdominal surgery were randomised to either routine management or personalised haemodynamic management requiring clinicians to maintain personal baseline cardiac index (determined at rest preoperatively) using an algorithm that guided intraoperative i.v. fluid and/or dobutamine administration. The primary outcome was a composite of major complications (European Perioperative Clinical Outcome definitions) or death within 30 days of surgery. Secondary outcomes included postoperative morbidity (assessed by a postoperative morbidity survey), hospital length of stay, mortality within 90 days of surgery, and neurocognitive function assessed after postoperative Day 3.

Results: The primary outcome occurred in 29.8% (28/94) of patients in the personalised management group, compared with 55.3% (52/94) of patients in the routine management group (relative risk: 0.54, 95% confidence interval [CI]: 0.38 to 0.77; absolute risk reduction: -25.5%, 95% CI: -39.2% to -11.9%; P<0.001). One patient assigned to the personalised management group, compared with five assigned to the routine management group, died within 30 days after surgery (P=0.097). There were no clinically relevant differences between the two groups for secondary outcomes.

Conclusions: In high-risk patients undergoing major abdominal surgery, personalised haemodynamic management reduces a composite outcome of major postoperative complications or death within 30 days after surgery compared with routine care.

Clinical Trial Registration: NCT02834377.
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http://dx.doi.org/10.1016/j.bja.2020.04.094DOI Listing
August 2020

Secreted Frizzled-Related Protein 4 (SFRP4) Is an Independent Prognostic Marker in Prostate Cancers Lacking TMPRSS2: ERG Fusions.

Pathol Oncol Res 2020 Oct 16;26(4):2709-2722. Epub 2020 Jul 16.

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

Secreted frizzled-related protein 4 (SFRP4) controls WNT signaling and is thought to play a role for tumor aggressiveness. Here, we analyzed a tissue microarray containing 11,152 prostate cancers with pathological, clinical and molecular data by immunohistochemistry. SFRP4 expression was higher in cancer than in non-neoplastic acinar cells. SFRP4 staining was seen in 64.9% of tumors and classified as weak in 33.2%, moderate in 23.9% and strong in 7.8% of cancers. SFRP4 overexpression was linked to advanced tumor stage, high classical/quantitative Gleason grade (p < 0.0001 each), lymph node metastasis (p = 0.0002), and a positive surgical margin (p = 0.0017). SFRP4 positivity was markedly more frequent in ERG positive (77.4%) than in ERG negative cancers (57.4% p < 0.0001). Subset analyses in 2725 cancers with and 3592 cancers without TMPRSS2:ERG fusion revealed that associations with tumor phenotype and patient outcome were largely driven by the subset of ERG negative tumors. In a multivariate analysis including various postoperative and prognostic clinico-pathological features, SFRP4 protein expression emerged as an independent prognostic parameter in ERG negative cancers. SFRP4 immunostaining was significantly linked with 10 of 11 previously analyzed chromosomal deletions (p < 0.05 each). In conclusion, high SFRP4 immunostaining is associated with poor prognosis and genomic instability in ERG negative prostate cancers.
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http://dx.doi.org/10.1007/s12253-020-00861-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7471174PMC
October 2020

The induction and function of the anti-inflammatory fate of T17 cells.

Nat Commun 2020 07 3;11(1):3334. Epub 2020 Jul 3.

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

T17 cells exemplify environmental immune adaptation: they can acquire both a pathogenic and an anti-inflammatory fate. However, it is not known whether the anti-inflammatory fate is merely a vestigial trait, or whether it serves to preserve the integrity of the host tissues. Here we show that the capacity of T17 cells to acquire an anti-inflammatory fate is necessary to sustain immunological tolerance, yet it impairs immune protection against S. aureus. Additionally, we find that TGF-β signalling via Smad3/Smad4 is sufficient for the expression of the anti-inflammatory cytokine, IL-10, in T17 cells. Our data thus indicate a key function of T17 cell plasticity in maintaining immune homeostasis, and dissect the molecular mechanisms explaining the functional flexibility of T17 cells with regard to environmental changes.
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http://dx.doi.org/10.1038/s41467-020-17097-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7335205PMC
July 2020

Polygenic and multifactorial scores for pancreatic ductal adenocarcinoma risk prediction.

J Med Genet 2020 Jun 26. Epub 2020 Jun 26.

Department of Biology, University of Pisa, Pisa, Italy.

Background: Most cases of pancreatic ductal adenocarcinoma (PDAC) are asymptomatic in early stages, and the disease is typically diagnosed in advanced phases, resulting in very high mortality. Tools to identify individuals at high risk of developing PDAC would be useful to improve chances of early detection.

Objective: We generated a polygenic risk score (PRS) for PDAC risk prediction, combining the effect of known risk SNPs, and carried out an exploratory analysis of a multifactorial score.

Methods: We tested the associations of the individual known risk SNPs on up to 2851 PDAC cases and 4810 controls of European origin from the PANcreatic Disease ReseArch (PANDoRA) consortium. Thirty risk SNPs were included in a PRS, which was computed on the subset of subjects that had 100% call rate, consisting of 839 cases and 2040 controls in PANDoRA and 6420 cases and 4889 controls from the previously published Pancreatic Cancer Cohort Consortium I-III and Pancreatic Cancer Case-Control Consortium genome-wide association studies. Additional exploratory multifactorial scores were constructed by complementing the genetic score with smoking and diabetes.

Results: The scores were associated with increased PDAC risk and reached high statistical significance (OR=2.70, 95% CI 1.99 to 3.68, p=2.54×10 highest vs lowest quintile of the weighted PRS, and OR=14.37, 95% CI 5.57 to 37.09, p=3.64×10, highest vs lowest quintile of the weighted multifactorial score).

Conclusion: We found a highly significant association between a PRS and PDAC risk, which explains more than individual SNPs and is a step forward in the direction of the construction of a tool for risk stratification in the population.
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http://dx.doi.org/10.1136/jmedgenet-2020-106961DOI Listing
June 2020

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

Up regulation of the Hippo signalling effector YAP1 is linked to early biochemical recurrence in prostate cancers.

Sci Rep 2020 06 2;10(1):8916. Epub 2020 Jun 2.

Institute of Pathology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.

The transcriptional coactivator YAP1 controls the balance between cell proliferation and apoptosis. YAP1 overexpression is linked to poor prognosis in many cancer types, yet its role in prostate cancer is unknown. Here, we applied YAP1 immunohistochemistry to a tissue microarray containing 17,747 clinical prostate cancer specimens. Cytoplasmic and nuclear YAP1 staining was seen in 81% and 63% of tumours. For both cytoplasmic and nuclear YAP1 staining, high levels were associated with advanced tumour stage, classical and quantitative Gleason grade, positive nodal stage, positive surgical margin, high KI67 labelling index, and early biochemical recurrence (p < 0.0001 each). The prognostic role of YAP1 staining was independent of established prognostic features in multivariate models (p < 0.001). Comparison with previously studied molecular markers identified associations between high YAP1 staining, TMPRSS2:ERG fusion (p < 0.0001), high androgen receptor (AR) expression (p < 0.0001), high Ki67 labelling index (p < 0.0001), and PTEN and 8p deletions (p < 0.0001 each). In conclusion, high YAP1 protein expression is an independent predictor of unfavourable disease course in prostate cancer. That cytoplasmic and nuclear YAP1 staining is equally linked to phenotype and prognosis fits well to a model where YAP1 activation during tumour progression includes up regulation, cytoplasmic accumulation and subsequent translocation to the nucleus.
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http://dx.doi.org/10.1038/s41598-020-65772-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7265544PMC
June 2020

TGF-β signaling in Th17 cells promotes IL-22 production and colitis-associated colon cancer.

Nat Commun 2020 05 25;11(1):2608. Epub 2020 May 25.

I. Department of Medicine, University Medical Center Hamburg-Eppendorf, 20246, Hamburg, Germany.

IL-22 has dual functions during tumorigenesis. Short term IL-22 production protects against genotoxic stress, whereas uncontrolled IL-22 activity promotes tumor growth; therefore, tight regulation of IL-22 is essential. TGF-β1 promotes the differentiation of Th17 cells, which are known to be a major source of IL-22, but the effect of TGF-β signaling on the production of IL-22 in CD4+ T cells is controversial. Here we show an increased presence of IL-17+IL-22+ cells and TGF-β1 in colorectal cancer compared to normal adjacent tissue, whereas the frequency of IL-22 single producing cells is not changed. Accordingly, TGF-β signaling in CD4+ T cells (specifically Th17 cells) promotes the emergence of IL-22-producing Th17 cells and thereby tumorigenesis in mice. IL-22 single producing T cells, however, are not dependent on TGF-β signaling. We show that TGF-β, via AhR induction, and PI3K signaling promotes IL-22 production in Th17 cells.
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http://dx.doi.org/10.1038/s41467-020-16363-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7248087PMC
May 2020

Upregulation of Phosphatase 1 Nuclear-Targeting Subunit (PNUTS) Is an Independent Predictor of Poor Prognosis in Prostate Cancer.

Dis Markers 2020 25;2020:7050146. Epub 2020 Apr 25.

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

Protein phosphatase 1 nuclear-targeting subunit (PNUTS) is ubiquitously expressed and associates with PTEN and protein phosphatase 1 (PP1) to control its activity. The role of PNUTS overexpression has hardly been studied in cancer. In this study, we used immunohistochemistry to quantitate PNUTS expression on a tissue microarray containing 17,747 clinical prostate cancer specimens. As compared to normal prostate epithelium, PNUTS expression was often higher in cancer. Among 12,235 interpretable tumors, PNUTS staining was negative in 21%, weak in 34%, moderate in 35%, and strong in 10% of cases. High PNUTS expression was associated with higher tumor stage, classical and quantitative Gleason grade, nodal stage, surgical margin, Ki67 labeling index, and early biochemical recurrence ( < 0.0001 each). PNUTS expression proved to be a moderate prognostic parameter with a maximal univariable Cox proportional hazard for PSA recurrence-free survival of 2.21 compared with 5.91 for Gleason grading. It was independent from established prognostic parameters in multivariable analysis. Comparison with molecular data available from earlier studies using the same TMA identified associations between high PNUTS expression and elevated androgen receptor expression ( < 0.0001), presence of G fusion ( < 0.0001), and 8 of 11 chromosomal deletions (3p13, 5q21, 8p21, 10q23, 12p13, 13q14, 16q24, and 17p13; < 0.05 each). Particularly strong associations with PTEN and 12p13 deletions ( < 0.0001 each) may indicate a functional relationship, which has already been established for PNUTS and PTEN. PNUTS had no additional role on outcome in PTEN-deleted cancers. In conclusion, the results of our study identify high PNUTS protein levels as a predictor of poor prognosis possibly linked to increased levels of genomic instability. PNUTS measurement, either alone or in combination, might be of clinical utility in prostate cancers.
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http://dx.doi.org/10.1155/2020/7050146DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7196962PMC
February 2021

Endoscopic vacuum therapy versus stenting for postoperative esophago-enteric anastomotic leakage: systematic review and meta-analysis.

Endoscopy 2020 08 21;52(8):632-642. Epub 2020 Apr 21.

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

Background: Esophageal anastomotic leakage still represents a challenging complication after esophageal surgery. Endoscopically placed self-expandable metal stents (SEMS) are the treatment of choice, but since the introduction of endoscopic vacuum therapy (EVT) for esophageal leakage 10 years ago, increasing evidence has demonstrated that EVT might be a superior alternative. Therefore, we performed a systematic review and meta-analysis to compare the effectiveness and related morbidity of SEMS and EVT in the treatment of esophageal leak.

Methods: We systematically searched for studies comparing SEMS and EVT to treat anastomotic leakage after esophageal surgery. Predefined end points including outcome, treatment success, endoscopy, treatment duration, hospitalization time, morbidity, and mortality were assessed and included in the meta-analysis.

Results: Five retrospective studies including 274 patients matched the inclusion criteria. Compared with stenting, EVT was significantly associated with a higher rate of leak closure (odds ratio [OR] 3.14, 95 % confidence interval [CI] 1.23 to 7.98), more endoscopic device changes (pooled median difference of 3.09; 95 %CI 1.54 to 4.64]), a shorter duration of treatment (pooled median difference -11.90 days; 95 %CI -18.59 to -5.21 days), and a lower mortality rate (OR 0.39, 95 %CI 0.18 to 0.83). There were no significant differences in short-term and major complications.

Conclusions: Owing to the retrospective quality of the studies with potential biases, the results of the meta-analysis must be interpreted with caution. However, the analysis indicates the potential benefit of EVT, which should be further investigated with standardized and prospectively collected data.
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http://dx.doi.org/10.1055/a-1149-1741DOI Listing
August 2020

Systemic interleukin 10 levels indicate advanced stages while interleukin 17A levels correlate with reduced survival in esophageal adenocarcinomas.

PLoS One 2020 16;15(4):e0231833. Epub 2020 Apr 16.

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

Introduction: Reflux promotes esophageal adenocarcinomas (EAC) creating a chronic inflammatory environment. EAC show an increasing incidence in the Western World and median survival rates are still low. The main reasons for poor prognosis despite new multimodal therapies are diagnosis of EACs at an already advanced stage and distant metastases. Hence, we wanted to investigate the presence of systemic inflammatory interleukins (IL) and their impact on patient prognosis.

Material And Methods: Systemic expression levels of pro- and anti-inflammatory markers (IL-2, IL-4, IL-6, IL-10, IL-17A and IL-22) in the sera of 43 EAC patients without neoadjuvant radiochemotherapy were measured by flow cytometric analysis. A correlation to clinicopathological data was performed. Log-rank and Cox regression analysis were used to investigate the impact on patient survival. 43 sera of age and gender matched healthy volunteers were used as controls.

Results: Increased systemic IL-6 (p = 0.044) and lower IL-17A (p = 0.002) levels were found in EAC patients as opposed to controls. A correlation of IL-10 levels with an increased T stage was found (p = 0.020). Also, systemic IL-10 levels were highly elevated in patients with distant metastasis (p<0.001). However, only systemic IL-17A levels had an influence on patient survival in multivariate analysis.

Conclusion: Systemic IL-6 levels are increased, while IL-17A levels are reduced in EAC patients compared to healthy controls. In addition, circulating IL-10 might help to identify patients with advanced disease and high IL-17A might indicate a limited prognosis.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0231833PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7162521PMC
August 2020

Expression and serum levels of the neural cell adhesion molecule L1-like protein (CHL1) in gastrointestinal stroma tumors (GIST) and its prognostic power.

Oncotarget 2020 Mar 31;11(13):1131-1140. Epub 2020 Mar 31.

Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg Eppendor, Hamburg, Germany.

Introduction: Diagnosis of gastrointestinal stroma tumors (GIST) is based on the histological evaluation of tissue specimens. Reliable systemic biomarkers are lacking. We investigated the local expression of the neural cell adhesion molecule L1-like protein (CHL1) in GIST and determined whether soluble CHL1 proteoforms could serve as systemic biomarkers.

Material And Methods: Expression of CHL1 was analyzed in primary tumor specimens and metastases. 58 GIST specimens were immunohistochemically stained for CHL1 on a tissue microarray (TMA). Systemic CHL1 levels were measured in sera derived from 102 GIST patients and 91 healthy controls by ELISA. Results were statistically correlated with clinicopathological parameters.

Results: CHL1 expression was detected in GIST specimens. Reduced tissue expression was significantly associated with advanced UICC stages ( = 0.036) and unfavorable tumor localization ( = 0.001). CHL1 serum levels are significantly elevated in GIST patients ( < 0.010). Elevated CHL1 levels were significantly associated with larger tumors ( = 0.023), advanced UICC stage ( = 0.021), and an increased Fletcher score ( = 0.041). Moreover, patients with a higher CHL1 serum levels displayed a significantly shortened recurrence free survival independent of other clinicopathological variables.

Conclusion: Local CHL1 expression and serum CHL1 levels show a reverse prognostic behavior, highlighting the relevance of proteolytic shedding of the molecule. The results of the study indicate a potential role of serum CHL1 as a diagnostic and prognostic marker in GIST.
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http://dx.doi.org/10.18632/oncotarget.27525DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7138165PMC
March 2020