Publications by authors named "Armin Wiegering"

72 Publications

The novel KIT exon 11 germline mutation K558N is associated with gastrointestinal stromal tumor, mastocytosis and seminoma development.

Genes Chromosomes Cancer 2021 Aug 2. Epub 2021 Aug 2.

Department of General, Visceral, Transplant, Vascular and Pediatric Surgery University Hospital Wuerzburg, Oberduerrbacherstrasse 6, Wuerzburg, Germany.

Familial gastrointestinal stromal tumors (GIST) are dominant genetic disorders that are caused by germline mutations of the type III receptor tyrosine kinase KIT. While sporadic mutations are frequently found in mastocytosis and GISTs, germline mutations of KIT have only been described in 39 families until now. We detected a novel germline mutation of KIT in exon 11 (p.Lys-558-Asn; K558N) in a patient from a kindred with several GISTs harboring different secondary somatic KIT mutations. Structural analysis suggests that the primary germline mutation alone is not sufficient to release the autoinhibitory region of KIT located in the transmembrane domain. Instead, the KIT kinase module becomes constitutively activated when K558N combines with different secondary somatic mutations. The identical germline mutation in combination with an additional somatic KIT mutation was detected in a second patient of the kindred with seminoma while a third patient within the family had a cutaneous mastocytosis. These findings suggest that the K558N mutation interferes with the juxtamembranous part of KIT, since seminoma and mastocystosis are usually not associated with Exon 11 mutations. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/gcc.22988DOI Listing
August 2021

[Impact of COVID-19 on elective and emergency colorectal surgery].

Chirurg 2021 Jul 13. Epub 2021 Jul 13.

Klinik und Poliklinik für Allgemein‑, Viszeral‑, Transplantations‑, Gefäß- und Kinderchirurgie, Universitätsklinikum Würzburg, 97080, Würzburg, Deutschland.

Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has led to far-reaching changes in the treatment reality in practically all fields of medicine.

Objective: Recommendations on the perioperative management with respect to SARS-CoV‑2 and presentation of the impact of the pandemic on colorectal surgery.

Material And Methods: A systematic literature search was carried out.

Results: Perioperative SARS-CoV‑2 infections lead to a clearly increased postoperative mortality and must be avoided by a structured bundle of measures. The worldwide limitations on screening investigations and treatment options can in the medium term result in an increased mortality due to colorectal cancer. In emergency treatment there was also a substantial reduction in case numbers with the danger of delayed interventions.

Conclusion: A rapid normalization of clinical treatment pathways in colorectal surgery is necessary to avoid long-term negative sequelae for patients.
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http://dx.doi.org/10.1007/s00104-021-01464-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8276841PMC
July 2021

[Robotic hernia repair : Part II: Robotic primary ventral and incisional hernia repair (rv-TAPP and r-Rives or r-TARUP). Video report and results of a series of 118 patients].

Chirurg 2021 Jul 13. Epub 2021 Jul 13.

Klinik für Viszeral‑, Gefäss- und Thoraxchirurgie, Kantonsspital Olten, Baslerstrasse 150, 4600, Olten, Schweiz.

Endoscopic management of umbilical and incisional hernias has adapted to the limitations of conventional laparoscopic instruments over the past 30 years. This includes the development of meshes for intraperitoneal placement (intraperitoneal onlay mesh, IPOM), with antiadhesive coatings; however, adhesions do occur in a significant proportion of these patients. Minimally invasive procedures result in fewer perioperative complications, but with a slightly higher recurrence rate. With the ergonomic resources of robotics, which offers angled instruments, it is now possible to implant meshes in a minimally invasively manner in different abdominal wall layers while achieving morphologic and functional reconstruction of the abdominal wall. This video article presents the treatment of ventral and incisional hernias with mesh implantation into the preperitoneal space (robot-assisted transabdominal preperitoneal ventral hernia repair, r‑ventral TAPP) as well as into the retrorectus space (r-Rives and robotic transabdominal retromuscular umbilical prosthetic repair, r‑TARUP, respectively). The results of a cohort study of 118 consecutive patients are presented and discussed with regard to the added value of the robotic technique in extraperitoneal mesh implantation and in the training of residents.
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http://dx.doi.org/10.1007/s00104-021-01450-5DOI Listing
July 2021

Lenvatinib halts aortic aneurysm growth by restoring smooth muscle cell contractility.

JCI Insight 2021 Jun 29. Epub 2021 Jun 29.

Department for Vascular and Endovascular Surgery, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany.

AAA is a disease with high morbidity and mortality, especially when ruptured. The rational of this study was to evaluate the repurposing of lenvatinib, a multi tyrosine kinase inhibitor, in limiting experimental abdominal aortic aneurysm (AAA) growth targeting vascular smooth muscle cells (VSMC) and angiogenesis. We applied systemic and local lenvatinib treatment to elastase-induced murine aortic aneurysms, and RNA profiling identified myosin heavy chain 11 (Myh11) as the most deregulated transcript. Daily oral treatment significantly reduced aneurysm formation in two independent mouse models. In addition, a large animal aneurysm model in hypercholesterolemic low-density lipoprotein receptor knockout (LDLR-/-) Yucatan minipigs was applied to endovascularly deliver Lenvatinib via drug-eluting balloons (DEB). Here, a single local endovascular delivery blocked AAA progression successfully compared to a DEB-delivered control treatment. Reduced VSMC proliferation and a restored contractile phenotype were observed in animal tissues (murine and porcine), as well as AAA patient-derived cells. Apart from increasing MYH11 levels, lenvatinib reduced downstream ERK signaling. Hence, Lenvatinib is a promising new therapy to limit aortic aneurysm expansion upon local endovascular delivery. The tyrosine kinase inhibitor was able to positively affect pathways of key relevance to human AAA disease, even in a potentially new local delivery using DEBs.
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http://dx.doi.org/10.1172/jci.insight.140364DOI Listing
June 2021

Robotic hernia surgery : Part I: Robotic inguinal hernia repair (r‑TAPP). Video report and results of a series of 302 hernia operations.

Chirurg 2021 Jun 29. Epub 2021 Jun 29.

Department of Visceral, Vascular and Thoracic Surgery, Cantonal Hospital Olten (soH), Baslerstrasse 150, 4600, Olten, Switzerland.

The treatment of inguinal hernias with open and minimally invasive procedures has reached a high standard in terms of outcome over the past 30 years. However, there is still need for further improvement, mainly in terms of reduction of postoperative seroma, chronic pain, and recurrence. This video article presents the endoscopic anatomy of the groin with regard to robotic transabdominal preperitoneal patch plasty (r‑TAPP) and illustrates the surgical steps of r‑TAPP with respective video sequences. The results of a cohort study of 302 consecutive hernias operated by r‑TAPP are presented and discussed in light of the added value of the robotic technique, including advantages for surgical training. r‑TAPP is the natural evolution of conventional TAPP and has the potential to become a new standard as equipment availability increases and material costs decrease. Future studies will also have to refine the multifaceted added value of r‑TAPP with new parameters.
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http://dx.doi.org/10.1007/s00104-021-01446-1DOI Listing
June 2021

MYC- and MIZ1-dependent vesicular transport of double-strand RNA controls immune evasion in pancreatic ductal adenocarcinoma.

Cancer Res 2021 Jun 18. Epub 2021 Jun 18.

Theodor Boveri Institute and Comprehensive Cancer Center Mainfranken, Biocenter, University of Würzburg

Deregulated expression of the MYC oncoprotein enables tumor cells to evade immune surveillance, but the mechanisms underlying this surveillance are poorly understood. We show here that endogenous MYC protects pancreatic ductal adenocarcinoma driven by KRASG12D and TP53R172H from eradication by the immune system. Deletion of TANK-Binding Kinase 1 (TBK1) bypassed the requirement for high MYC expression. TBK1 was active due to the accumulation of double-stranded RNA (dsRNA), which was derived from inverted repetitive elements localized in introns of nuclear genes. Nuclear-derived dsRNA is packaged into extracellular vesicles and subsequently recognized by toll-like receptor 3 (TLR3) to activate TBK1 and downstream MHC class I expression in an autocrine or paracrine manner before being degraded in lysosomes. MYC suppressed loading of dsRNA onto TLR3 and its subsequent degradation via association with MIZ1. Collectively, these findings suggest that MYC and MIZ1 suppress a surveillance pathway that signals perturbances in mRNA processing to the immune system, which facilitates immune evasion in pancreatic ductal adenocarcinoma.
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http://dx.doi.org/10.1158/0008-5472.CAN-21-1677DOI Listing
June 2021

Successful surgical closure of infected abdominal wounds following preconditioning with negative pressure wound therapy.

Langenbecks Arch Surg 2021 Jun 17. Epub 2021 Jun 17.

Department of General, Visceral, Transplantation, Vascular and Pediatric Surgery, University Hospital Würzburg, Oberduerrbacherstr. 6, 97080, Würzburg, Germany.

Purpose: Traditionally, previous wound infection was considered a contraindication to secondary skin closure; however, several case reports describe successful secondary wound closure of wounds "preconditioned" with negative pressure wound therapy (NPWT). Although this has been increasingly applied in daily practice, a systematic analysis of its feasibility has not been published thus far. The aim of this study was to evaluate secondary skin closure in previously infected abdominal wounds following treatment with NPWT.

Methods: Single-center retrospective analysis of patients with infected abdominal wounds treated with NPWT followed by either secondary skin closure referenced to a group receiving open wound therapy. Endpoints were wound closure rate, wound complications (such as recurrent infection or hernia), and perioperative data (such as duration of NPWT or hospitalization parameters).

Results: One hundred ninety-eight patients during 2013-2016 received a secondary skin closure after NPWT and were analyzed and referenced to 67 patients in the same period with open wound treatment after NPWT. No significant difference in BMI, chronic immunosuppressive medication, or tobacco use was found between both groups. The mean duration of hospital stay was 30 days with a comparable duration in both patient groups (29 versus 33 days, p = 0.35). Interestingly, only 7.7% of patients after secondary skin closure developed recurrent surgical site infection and in over 80% of patients were discharged with closed wounds requiring only minimal outpatient wound care.

Conclusion: Surgical skin closure following NPWT of infected abdominal wounds is a good and safe alternative to open wound treatment. It prevents lengthy outpatient wound therapy and is expected to result in a higher quality of life for patients and reduce health care costs.
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http://dx.doi.org/10.1007/s00423-021-02221-wDOI Listing
June 2021

Correction to: CIP2A regulates MYC translation (via its 5'UTR) in colorectal cancer.

Int J Colorectal Dis 2021 Jun 4. Epub 2021 Jun 4.

Department of Biochemistry and Molecular Biology, Biocenter, University of Würzburg, Würzburg, Germany.

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http://dx.doi.org/10.1007/s00384-021-03960-4DOI Listing
June 2021

[Robotic hernia surgery : Part I: Robotic inguinal hernia repair (r‑TAPP). Video report and results of a series of 302 hernia operations].

Chirurg 2021 Aug 1;92(8):707-720. Epub 2021 Jun 1.

Klinik für Viszeral‑, Gefäss- und Thoraxchirurgie, Kantonsspital Olten, Baslerstr. 150, 4600, Olten, Schweiz.

The treatment of inguinal hernias with open and minimally invasive procedures has reached a high standard in terms of outcome over the past 30 years. However, there is still need for further improvement, mainly in terms of reduction of postoperative seroma, chronic pain, and recurrence. This video article presents the endoscopic anatomy of the groin with regard to robotic transabdominal preperitoneal patch plasty (r‑TAPP) and illustrates the surgical steps of r‑TAPP with respective video sequences. The results of a cohort study of 302 consecutive hernias operated by r‑TAPP are presented and discussed in light of the added value of the robotic technique, including advantages for surgical training. r‑TAPP is the natural evolution of conventional TAPP and has the potential to become a new standard as equipment availability increases and material costs decrease. Future studies will also have to refine the multifaceted added value of r‑TAPP with new parameters.
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http://dx.doi.org/10.1007/s00104-021-01425-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8324587PMC
August 2021

Preoperative Liver Function Guiding HCC Resection in Normal and Cirrhotic Liver.

Visc Med 2021 Mar 12;37(2):94-101. Epub 2020 Jun 12.

Department of General, Visceral and Transplantation Surgery, University Hospital of Würzburg, Würzburg, Germany.

Background: Liver resection is the most effective available therapy for patients with hepatocellular carcinoma (HCC). The accurate selection of patients for surgery requires determination of technical resectability and the risk of recurrence, as well as assessment of liver function and functional reserve to avoid postoperative liver failure. Previous studies have underlined the effectiveness and reliability of the LiMAx® test to evaluate liver function preoperatively. Nevertheless, data concerning HCC evaluation are lacking.

Methods: From 2014 to 2019, 92 patients with HCC underwent additional assessment of liver function using the LiMAx test prior to decision for or against liver resection. Preoperative LiMAx results were compared between cirrhotic and noncirrhotic liver. The clinical decision for surgery was evaluated applying the various liver function parameters available.

Results: Forty-six patients underwent liver resection. The LiMAx results were higher in resected patients (388 vs. 322 µg/kg/h; = 0.004). LiMAx values were an independent risk factor for the presence of liver cirrhosis in multivariate analysis. In 17 patients, surgical treatment was cancelled due to major impairment of liver function. Only 4 out of 46 resected patients presented with post-hepatectomy liver failure (PHLF) grade ≥B. Histologic assessment revealed liver cirrhosis in 10 resected patients without PHLF.

Conclusion: Preoperative determination of liver function by the LiMAx test enables effective and safe patient selection for HCC resection in both cirrhotic and noncirrhotic liver.
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http://dx.doi.org/10.1159/000508172DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8077495PMC
March 2021

Prognostic impact of additive chemotherapy after curative resection of metachronous colorectal liver metastasis: a single-centre retrospective study.

BMC Cancer 2021 May 3;21(1):490. Epub 2021 May 3.

Department of General, Visceral, Transplant, Vascular and Pediatric Surgery, University Hospital of Würzburg, Oberdürrbacherstr. 6, 97080, Würzburg, Germany.

Background: A prognostic benefit of additive chemotherapy in patients following resection of metachronous colorectal liver metastases (CRLM) remains controversial. Therefore, the goal of this retrospective study was to investigate the impact of perioperative chemotherapy on disease-free survival (DFS) and overall survival (OS) of patients after curative resection of metachronous CRLM.

Methods: In a retrospective single-centre study, patients after curative resection of metachronous CRLM were included and analysed for DFS and OS with regard to the administration of additive chemotherapy. The Kaplan-Meier method was applied to compare DFS and OS while Cox regression models were used to identify independent prognostic variables.

Results: Thirty-four of 75 patients were treated with additive 5-FU based chemotherapy. OS was significantly prolonged in this patient subgroup (62 vs 57 months; p = 0.032). Additive chemotherapy significantly improved 10-year survival rates (42% vs 0%, p = 0.023), but not 5-year survival (58% vs 42%, p = 0.24). Multivariate analysis identified additive chemotherapy (p = 0.016, HR 0.44, 95% CI 0.23-0.86), more than five CRLM (p = 0.026, HR 2.46, 95% CI 1.16-10.32) and disease recurrence (0.009, HR 2.70, 95% CI 1.29-5.65) as independent risk factors for OS.

Conclusion: Additive chemotherapy significantly prolonged OS and 10-year survival in patients after curative resection of metachronous CRLM. Randomized clinical trials are needed in the future to identify optimal chemotherapy regimens for those patients.
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http://dx.doi.org/10.1186/s12885-021-07941-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8091534PMC
May 2021

Laparoscopic appendectomy versus antibiotic treatment for acute appendicitis-a systematic review.

Int J Colorectal Dis 2021 Apr 14. Epub 2021 Apr 14.

Department of General, Visceral, Transplantation, Vascular and Pediatric Surgery, University Hospital, University of Wuerzburg, Oberduerrbacherstr. 6, 97080, Wuerzburg, Germany.

Background: Over the last years, laparoscopic appendectomy has progressively replaced open appendectomy and become the current gold standard treatment for suspected, uncomplicated appendicitis. At the same time, though, it is an ongoing discussion that antibiotic therapy can be an equivalent treatment for patients with uncomplicated appendicitis. The aim of this systematic review was to determine the safety and efficacy of antibiotic therapy and compare it to the laparoscopic appendectomy for acute, uncomplicated appendicitis.

Methods: The PubMed database, Embase database, and Cochrane library were scanned for studies comparing laparoscopic appendectomy with antibiotic treatment. Two independent reviewers performed the study selection and data extraction. The primary endpoint was defined as successful treatment of appendicitis. Secondary endpoints were pain intensity, duration of hospitalization, absence from work, and incidence of complications.

Results: No studies were found that exclusively compared laparoscopic appendectomy with antibiotic treatment for acute, uncomplicated appendicitis.

Conclusions: To date, there are no studies comparing antibiotic treatment to laparoscopic appendectomy for patients with acute uncomplicated appendicitis, thus emphasizing the lack of evidence and need for further investigation.
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http://dx.doi.org/10.1007/s00384-021-03927-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8045433PMC
April 2021

Case Report: Abdominal Lymph Node Metastases of Parathyroid Carcinoma: Diagnostic Workup, Molecular Diagnosis, and Clinical Management.

Front Endocrinol (Lausanne) 2021 23;12:643328. Epub 2021 Mar 23.

Department of Internal Medicine I, Division of Endocrinology and Diabetes, University Hospital, University of Würzburg, Würzburg, Germany.

Parathyroid carcinoma (PC) is an orphan malignancy accounting for only ~1% of all cases with primary hyperparathyroidism. The localization of recurrent PC is of critical importance and can be exceedingly difficult to diagnose and sometimes futile when common sites of recurrence in the neck and chest cannot be confirmed. Here, we present the diagnostic workup, molecular analysis and multimodal therapy of a 46-year old woman with the extraordinary manifestation of abdominal lymph node metastases 12 years after primary diagnosis of PC. The patient was referred to our endocrine tumor center in 2016 with the aim to localize the tumor causative of symptomatic biochemical recurrence. In view of the extensive previous workup we decided to perform [18F]FDG-PET-CT. A pathological lymph node in the liver hilus showed slightly increased FDG-uptake and hence was suspected as site of recurrence. Selective venous sampling confirmed increased parathyroid hormone concentration in liver veins. Abdominal lymph node metastasis was resected and histopathological examination confirmed PC. Within four months, the patient experienced biochemical recurrence and based on high tumor mutational burden detected in the surgical specimen by whole exome sequencing the patient received immunotherapy with pembrolizumab that led to a biochemical response. Subsequent to disease progression repeated abdominal lymph node resection was performed in 10/2018, 01/2019 and in 01/2020. Up to now (12/2020) the patient is biochemically free of disease. In conclusion, a multimodal diagnostic approach and therapy in an interdisciplinary setting is needed for patients with rare endocrine tumors. Molecular analyses may inform additional treatment options including checkpoint inhibitors such as pembrolizumab.
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http://dx.doi.org/10.3389/fendo.2021.643328DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8021949PMC
March 2021

Brain Metastases from Colorectal Cancer: A Systematic Review of the Literature and Meta-Analysis to Establish a Guideline for Daily Treatment.

Cancers (Basel) 2021 Feb 21;13(4). Epub 2021 Feb 21.

Department of General, University Hospital Wuerzburg, Visceral, Transplant, Vascular and Paediatric Surgery, 97084 Wuerzburg, Germany.

Colorectal cancer (CRC) is the third most common malignancy worldwide. Most patients with metastatic CRC develop liver or lung metastases, while a minority suffer from brain metastases. There is little information available regarding the presentation, treatment, and overall survival of brain metastases (BM) from CRC. This systematic review and meta-analysis includes data collected from three major databases (PubMed, Cochrane, and Embase) based on the key words "brain", "metastas*", "tumor", "colorectal", "cancer", and "malignancy". In total, 1318 articles were identified in the search and 86 studies matched the inclusion criteria. The incidence of BM varied between 0.1% and 11.5%. Most patients developed metastases at other sites prior to developing BM. Lung metastases and mutations were described as risk factors for additional BM. Patients with BM suffered from various symptoms, but up to 96.8% of BM patients were asymptomatic at the time of BM diagnosis. Median survival time ranged from 2 to 9.6 months, and overall survival (OS) increased up to 41.1 months in patients on a multimodal therapy regimen. Several factors including age, blood levels of carcinoembryonic antigen (CEA), multiple metastases sites, number of brain lesions, and presence of the mutation were predictors of OS. For BM diagnosis, MRI was considered to be state of the art. Treatment consisted of a combination of surgery, radiation, or systemic treatment.
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http://dx.doi.org/10.3390/cancers13040900DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7924831PMC
February 2021

Ephrin receptor A2, the epithelial receptor for Epstein-Barr virus entry, is not available for efficient infection in human gastric organoids.

PLoS Pathog 2021 02 17;17(2):e1009210. Epub 2021 Feb 17.

Research Centre for Infectious Diseases, Institute for Molecular Infection Biology, Julius Maximilian University of Wuerzburg, Wuerzburg, Germany.

Epstein-Barr virus (EBV) is best known for infection of B cells, in which it usually establishes an asymptomatic lifelong infection, but is also associated with the development of multiple B cell lymphomas. EBV also infects epithelial cells and is associated with all cases of undifferentiated nasopharyngeal carcinoma (NPC). EBV is etiologically linked with at least 8% of gastric cancer (EBVaGC) that comprises a genetically and epigenetically distinct subset of GC. Although we have a very good understanding of B cell entry and lymphomagenesis, the sequence of events leading to EBVaGC remains poorly understood. Recently, ephrin receptor A2 (EPHA2) was proposed as the epithelial cell receptor on human cancer cell lines. Although we confirm some of these results, we demonstrate that EBV does not infect healthy adult stem cell-derived gastric organoids. In matched pairs of normal and cancer-derived organoids from the same patient, EBV only reproducibly infected the cancer organoids. While there was no clear pattern of differential expression between normal and cancer organoids for EPHA2 at the RNA and protein level, the subcellular location of the protein differed markedly. Confocal microscopy showed EPHA2 localization at the cell-cell junctions in primary cells, but not in cancer cell lines. Furthermore, histologic analysis of patient tissue revealed the absence of EBV in healthy epithelium and presence of EBV in epithelial cells from inflamed tissue. These data suggest that the EPHA2 receptor is not accessible to EBV on healthy gastric epithelial cells with intact cell-cell contacts, but either this or another, yet to be identified receptor may become accessible following cellular changes induced by inflammation or transformation, rendering changes in the cellular architecture an essential prerequisite to EBV infection.
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http://dx.doi.org/10.1371/journal.ppat.1009210DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7935236PMC
February 2021

Changes in the management of acute appendicitis during the COVID-19 pandemic.

Langenbecks Arch Surg 2021 03 3;406(2):503-504. Epub 2021 Feb 3.

Department of General, Visceral, Transplantation, Vascular and Pediatric Surgery, University Hospital, University of Würzburg, Oberdürrbacherstr 6, 97080, Würzburg, Germany.

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http://dx.doi.org/10.1007/s00423-021-02099-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7854877PMC
March 2021

Defining the Scope of Antimicrobial Stewardship Interventions on the Prescription Quality of Antibiotics for Surgical Intra-Abdominal Infections.

Antibiotics (Basel) 2021 Jan 14;10(1). Epub 2021 Jan 14.

Department of General-, Visceral-, Transplant-, Vascular- and Paediatric Surgery, University Hospital of Würzburg, 97080 Würzburg, Germany.

Background: The aim of this study was to assess the impact of antimicrobial stewardship interventions on surgical antibiotic prescription behavior in the management of non-elective surgical intra-abdominal infections, focusing on postoperative antibiotic use, including the appropriateness of indications.

Methods: A single-center quality improvement study with retrospective evaluation of the impact of antimicrobial stewardship measures on optimizing antibacterial use in intra-abdominal infections requiring emergency surgery was performed. The study was conducted in a tertiary hospital in Germany from January 1, 2016, to January 30, 2020, three years after putting a set of antimicrobial stewardship standards into effect.

Results: 767 patients were analyzed ( = 495 in 2016 and 2017, the baseline period; = 272 in 2018, the antimicrobial stewardship period). The total days of therapy per 100 patient days declined from 47.0 to 42.2 days ( = 0.035). The rate of patients receiving postoperative therapy decreased from 56.8% to 45.2% ( = 0.002), comparing both periods. There was a significant decline in the rate of inappropriate indications (17.4% to 8.1 %, = 0.015) as well as a significant change from broad-spectrum to narrow-spectrum antibiotic use (28.8% to 6.5%, ≤ 0.001) for postoperative therapy. The significant decline in antibiotic use did not affect either clinical outcomes or the rate of postoperative wound complications.

Conclusions: Postoperative antibiotic use for intra-abdominal infections could be significantly reduced by antimicrobial stewardship interventions. The identification of inappropriate indications remains a key target for antimicrobial stewardship programs.
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http://dx.doi.org/10.3390/antibiotics10010073DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7828676PMC
January 2021

Systematic review and meta-analysis on volume-outcome relationship of abdominal surgical procedures in Germany.

Int J Surg 2021 Feb 9;86:24-31. Epub 2021 Jan 9.

Department of General, Visceral, Transplant, Vascular and Pediatric Surgery University Hospital Würzburg, Oberduerrbacherstrasse 6, 97080, Wuerzburg, Germany; Comprehensive Cancer Center Mainfranken, University Hospital Würzburg, Germany; Department of Biochemistry and Molecular Biology University of Würzburg Würzburg, Germany. Electronic address:

Background: In the past, for a number of abdominal surgical interventions a correlation between treatment volume of a hospital and the patient's outcome was shown in national and international studies.

Methods: Based on a systematic literature search we analyzed the absolute and risk-adjusted in-house lethality as well as the rate of complications and the failure to rescue after abdominal surgery in Germany. The hospitals were grouped in quintiles according to the volume of treatment.

Results: 11 studies including more than 2 million patients were identified and surgeries for the treatment of 9 disease conditions were studied. The meta-analysis shows a significantly lower absolute and risk-adjusted in-house mortality for surgery in hospitals with high treatment volumes compared to low volume hospitals. In the context of subgroup analysis, this effect is demonstrated especially for complex surgical procedures. The failure to rescue in patients suffering from sepsis is significantly lower in high volume centers compared to low volume centers.

Conclusion: This systematic review and meta-analysis shows on more than 2 million patients that there is a volume-outcome relationship for the surgical treatment of abdominal diseases in Germany across various organ systems, which is particularly true for complex interventions.
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http://dx.doi.org/10.1016/j.ijsu.2020.12.010DOI Listing
February 2021

Impact of the COVID-19 pandemic on appendicitis treatment in Germany-a population-based analysis.

Langenbecks Arch Surg 2021 Mar 9;406(2):377-383. Epub 2021 Jan 9.

Department of General, Visceral, Transplantation, Vascular and Pediatric Surgery, University Hospital, University of Wuerzburg, Oberduerrbacherstr. 6, 97080, Wuerzburg, Germany.

Purpose: Acute appendicitis is one of the most common reasons for emergency medical consultation. While simple appendicitis can be treated with antibiotics or surgery, complex appendicitis including gangrene, abscess, and perforation requires appendectomy. During the COVID-19 pandemic in early 2020, an overall drop in emergency room consultations was observed. We therefore aimed to investigate the incidence and treatment strategies of acute appendicitis during that period.

Methods: Data of insurance holders with the ICD code for "acute appendicitis" or OPS procedure of appendectomy of a major health insurance company in Germany were analyzed retrospectively. Groups were built, containing of the means of March-June of 2017, 2018, and 2019, defined as "pre-COVID group" with the "COVID group," defined as data from March to June of 2020. Data was analyzed by age, sex, comorbidities, length of hospital stay, diagnoses, and treatment. Data of the COVID group was analyzed for simultaneous COVID-19 infection.

Results: During the COVID-19 pandemic of early 2020, an overall reduction by 12.9% of patients presenting with acute appendicitis was noticeable. These results were mainly due to decreased rates of uncomplicated appendicitis, while complicated appendicitis was scarcely affected. Especially in the group of females < 40 years, a drastic reduction was visible. Rates of extended surgery did not change. Likewise, the complication rate like appendix stump leakage or need for re-operation did not differ. In March 2020, 4.8% of acute appendicitis patients had concomitant COVID-19 infection.

Conclusion: In line with the overall drop of emergency room visits during the COVID-19 pandemic of spring 2020 in Germany, a significantly lowered number of patients with uncomplicated appendicitis were noticeable, whereas complicated appendicitis did not differ. Also, treatment and complication rate of acute appendicitis did not change. These findings might be a hint that acute appendicitis is not a progressing disease but caused by different entities for uncomplicated and complicated appendicitis and therefore another clue that uncomplicated appendicitis can be treated with antibiotics or observation. Nevertheless provided data does not cover outpatient treatment; therefore, no statement observation or antibiotics in outpatients can be made.
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http://dx.doi.org/10.1007/s00423-021-02081-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7794073PMC
March 2021

Desmoplastic Small Round Cell Tumors: A review with focus on clinical management and therapeutic options.

Cancer Treat Rev 2021 Feb 24;93:102140. Epub 2020 Dec 24.

Department of General, Visceral, Transplant, Vascular and Pediatric Surgery, University Hospital, University of Wuerzburg, Oberduerrbacherstr. 2, 97080 Wuerzburg, Germany; Comprehensive Cancer Centre Mainfranken, University of Wuerzburg Medical Center, Josef-Schneiderstr. 6, 97080 Wuerzburg, Germany; Department of Biochemistry and Molecular Biology, University of Wuerzburg, Germany. Electronic address:

Desmoplastic Small Round Cell Tumors (DSRCTs) are an entity of rare, aggressive soft tissue sarcomas described by Gerald and Rosai in 1989. It predominantly affects male adolescents and young adults, with a peak incidence between an age of 20 and 30 years. Typically, DSRCT demonstrate as multiple small tumor nodules within the abdominal cave, retroperitoneum and pelvis. In more than 50% of the cases, the neoplasm presents metastatic at the timepoint of diagnosis. Histologically, DSRCTs have a characteristic morphology with sharply demarcated islands of uniform small round cells in abundant desmoplastic stroma organized in loose extracellular matrix. Immunohistochemistry reveals a polyphenotypic differentiation with co-expression of epithelial, myogenic, mesenchymal and neural markers. The morphology is highly variable and can hinder diagnosis. The most consistent molecular characteristic of DSRCT is the reciprocal t(11;22)(p13q12) translocation. This mutation leads to a formation of the EWSR1-WT1 fusion oncogene, which encodes for a chimeric protein with transcriptional regulatory activity and is regarded as driving source of the disease. To date, there is no standardized concept for clinical management, staging and treatment. Patients receive an aggressive multimodal therapeutic approach consisting of chemotherapy, radical surgical procedures, hyperthermic, intraperitoneal chemotherapy (HIPEC) and radiation. New targeted therapies are used in experimental settings as salvage therapy. So far, none of these therapies showed significant long-term success. This review gives an overview of diagnostic difficulties and pitfalls, discusses therapeutic strategies and highlights options for clinical management.
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http://dx.doi.org/10.1016/j.ctrv.2020.102140DOI Listing
February 2021

[Laparostoma-Avoidance and treatment of complications].

Chirurg 2021 Mar;92(3):283-296

Klinik und Poliklinik für Allgemein‑, Viszeral‑, Transplantations‑, Gefäß- und Kinderchirurgie, Oberdürrbacher Straße 6, 97080, Würzburg, Deutschland.

The open abdomen (OA) is an established concept for treating severe abdominal diseases. The most frequent reasons for placement of an open abdomen are abdominal sepsis (e.g. from intestinal perforation or anastomotic leakage), severe abdominal organ injury and abdominal compartment syndrome. The pathophysiology is much more complex than the surgeon's eye can see in an OA. The temporary closure of the abdominal wall ensures sufficient drainage of infected ascites, protection of the intestinal loops and conditioning of the abdominal wall in order to be able carry out definitive closure of the abdominal wall at the end of the surgical treatment. Negative peritoneal pressure therapy combined with fascia traction (with or without mesh) is well-established in the management of an open abdomen.
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http://dx.doi.org/10.1007/s00104-020-01322-4DOI Listing
March 2021

[Evidence in minimally invasive oncological surgery of the colon and rectum].

Chirurg 2021 Apr;92(4):334-343

Klinik und Poliklinik für Allgemein‑, Viszeral‑, Transplantations‑, Gefäß- und Kinderchirurgie, Zentrum für operative Medizin, Universitätsklinikum Würzburg, Oberdürrbacherstr. 6, 97080, Würzburg, Deutschland.

An essential component of the treatment of colorectal cancer is a resection of the tumor-bearing segment of the bowels. After the development of minimally invasive procedures the feasibility and safety in oncological, colorectal surgery was questioned. The broad study situation for colon cancer over the last years showed predominantly consistent benefits during the perioperative phase and non-inferiority concerning long-term oncological outcomes. The implementation of laparoscopic rectal resection was more hesitant due to the complexity of the procedure and insufficient study data; however, overall the short-term benefits seem to be maintained and laparoscopic rectal resection is thought to be noninferior to open resection in the long run even though findings on the quality of the resected specimen are heterogeneous. Accordingly, most guidelines now include a recommendation of laparoscopic resection for colorectal cancer. The limitation with respect to an achievable oncological equivalency of resection takes account of the complexity and the requirements of the intervention only in the setting of rational selection of patients and sufficient experience of the surgeon.
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http://dx.doi.org/10.1007/s00104-020-01320-6DOI Listing
April 2021

The Effect of Day of the Week on Morbidity and Mortality From Colorectal and Pancreatic Surgery.

Dtsch Arztebl Int 2020 Aug;117(31-32):521-527

Department of General, Visceral, Transplant, Vascular, and Pediatric Surgery, Center for Operative Medicine, University Hospital of Würzburg, Würzburg, Germany; Comprehensive Cancer Center Mainfranken, University Hospital of Würzburg, Würzburg, Germany; Institute of Biochemistry and Molecular Biology I, University of Würzburg, Würzburg, Germany.

Background: A number of studies have revealed higher postoperative mortality after operations that were performed toward the end of the week. It is not yet known whether a day-of-the-week effect exists after visceral surgical procedures for cancer in Germany.

Methods: Data on resections of carcinomas of the colon, rectum (2010-2017), and head of the pancreas (2014-2017) (n = 19 703) that had been prospectively acquired by the Study, Documentation, and Quality Center of the German Society for General and Visceral Surgery were analyzed in relation to the day of the week on which the operation was performed. The primary endpoint was postoperative 30-day mortality; the secondary endpoints were complications, length of hospital stay, and MTL30 (a combined outcome criterion that is positive if the patient has died, is still in the hospital, or has been transferred to another acute care hospital 30 days after the index procedure).

Results: Resections of colon carcinomas that were performed on Mondays were associated with more advanced tumor stages (T4: 18.4% vs. 15.7%, p <0.001), higher 30-day mortality (3.5% vs. 2.3%, p = 0.004), and a more frequently positive MTL30 (10.5% vs. 8.5%, p = 0.004). Among patients who underwent pancreatic head resections, those whose procedures were on Tuesday had higher mortality (6.2% vs. 3.8%; p = 0.021). Among those who underwent surgery for rectal carcinoma, the day of the week on which the procedure was performed had no effect on postoperative morality. Multivariate analysis revealed that the independent risk factors for postoperative mortality were colonic resection on a Monday (odds ratio [OR]: 1.45; 95% confidence interval [1.11; 1.92], p = 0.008) and pancreatic head resection on a Tuesday (OR: 1.88 [1.18; 2.91], p = 0.006).

Conclusion: Elective surgery for carcinoma of the colon or pancreatic head is associated with slightly higher mortality if per - formed toward the beginning of the week. On the other hand, the day of the week has no effect on the outcome of surgery for rectal carcinoma.
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http://dx.doi.org/10.3238/arztebl.2020.0521DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7658684PMC
August 2020

CIP2A regulates MYC translation (via its 5'UTR) in colorectal cancer.

Int J Colorectal Dis 2021 May 19;36(5):911-918. Epub 2020 Oct 19.

Department of Biochemistry and Molecular Biology, Biocenter, University of Würzburg, Würzburg, Germany.

Background: Deregulated expression of MYC is a driver of colorectal carcinogenesis, suggesting that decreasing MYC expression may have significant therapeutic value. CIP2A is an oncogenic factor that regulates MYC expression. CIP2A is overexpressed in colorectal cancer (CRC), and its expression levels are an independent marker for long-term outcome of CRC. Previous studies suggested that CIP2A controls MYC protein expression on a post-transcriptional level.

Methods: To determine the mechanism by which CIP2A regulates MYC in CRC, we dissected MYC translation and stability dependent on CIP2A in CRC cell lines.

Results: Knockdown of CIP2A reduced MYC protein levels without influencing MYC stability in CRC cell lines. Interfering with proteasomal degradation of MYC by usage of FBXW7-deficient cells or treatment with the proteasome inhibitor MG132 did not rescue the effect of CIP2A depletion on MYC protein levels. Whereas CIP2A knockdown had marginal influence on global protein synthesis, we could demonstrate that, by using different reporter constructs and cells expressing MYC mRNA with or without flanking UTR, CIP2A regulates MYC translation. This interaction is mainly conducted by the MYC 5'UTR.

Conclusions: Thus, instead of targeting MYC protein stability as reported for other tissue types before, CIP2A specifically regulates MYC mRNA translation in CRC but has only slight effects on global mRNA translation. In conclusion, we propose as novel mechanism that CIP2A regulates MYC on a translational level rather than affecting MYC protein stability in CRC.
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http://dx.doi.org/10.1007/s00384-020-03772-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8178152PMC
May 2021

Mortality and complication management after surgery for colorectal cancer depending on the DKG minimum amounts for hospital volume.

Eur J Surg Oncol 2021 Apr 25;47(4):850-857. Epub 2020 Sep 25.

Department of General, Visceral, Vascular and Pediatric Surgery, University Hospital, University of Wuerzburg, Oberduerrbacherstr. 2, 97080, Wuerzburg, Germany; Comprehensive Cancer Centre Mainfranken, University of Wuerzburg Medical Center, Josef-Schneiderstr. 6, 97080, Wuerzburg, Germany; Department of Biochemistry and Molecular Biology, University of Wuerzburg, Germany. Electronic address:

Background: The German Cancer Society ("Deutsche Krebsgesellschaft"; DKG) certifies on a volunteer base colorectal cancer centers based on, among other things, minimum operative amounts (at least 30 oncological colon cancer resections and 20 oncological rectal cancer resections per year). In this work, nationwide hospital mortality and death after documented complications ('Failure to Rescue' = FtR) were evaluated depending on the fulfillment of the minimum amounts.

Methods: This is a retrospective analysis of the nationwide hospital billing data (DRG data, 2012-2017). Categorization is based on the DKG minimum quantities (fully, partially or not fulfilled).

Results: Of 287,227 patients analyzed, 56.5% were operated in centers that met the DKG minimum amounts. The overall hospital mortality rate was 5.0%. In centers which met the minimum quantities, it was significantly lower (4.3%) than in hospitals which partially (5.7%) or not (6.2%) met the minimum quantities. The risk-adjusted hospital mortality rate for patients in hospitals who meet the minimum amount was 20% lower (OR 0.80; 95% CI [0.74-0.87], p < 0.001). For complications, both surgical and non-surgical, there was an unadjusted and adjusted lower FtR in hospitals that met the minimum amounts (e.g. anastomotic leak: 11.2% vs. 15.6%, p < 0.001; pulmonary artery embolism 21.3% vs. 28.2%, p = 0.001).

Conclusion: There is a 1/3 lower mortality and FtR rate after surgery for a colon or rectal cancer in centers fulfilling the DKG minimum amounts. The presented data implicate that there is an urgent need for a nationwide centralization program.
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http://dx.doi.org/10.1016/j.ejso.2020.09.024DOI Listing
April 2021

Nationwide effect of high procedure volume in lung cancer surgery on in-house mortality in Germany.

Lung Cancer 2020 11 31;149:78-83. Epub 2020 Aug 31.

Department of Thoracic Surgery, Thoraxklinik at Heidelberg University Hospital, Roentgenstrasse 1, 69126 Heidelberg, Germany; Translational Lung Research Center Heidelberg (TLRC), German Center for Lung Research (DZL), Im Neuenheimer Feld 156, 69120 Heidelberg, Germany. Electronic address:

Background: The literature reports that hospital caseload volume is associated with survival for lung cancer resection. The aim of this study is to explore this association in a nationwide setting according to individual hospital caseload volume of every inpatient case in Germany.

Methods: This retrospective analysis of nationwide hospital discharge data in Germany between 2014 and 2017 comprises 121,837 patients of whom 36,051 (29.6 %) underwent surgical anatomic resection. Hospital volumes were defined according to the number of patient resections for lung cancer in each hospital, and patients were categorized into 5 quintiles based on hospital caseload volume. A logistic regression model accounting for death according to sex, age, comorbidity, and resection volume was calculated, and effect modification was evaluated using the Mantel-Haenszel method.

Results: In-house mortality ranged from 2.1 % in very high-volume centers to 4.0 % in very low-volume hospitals (p < 0.01). In multivariable logistic regression analysis, lower in-house mortality in very high-volume centers performing > 140 anatomic lung resections per year was observed compared with very low-volume centers performing < 27 resections (OR, 0.58; CI, 0.46 to 0.72; p < 0.01). This relationship also held for failure to rescue rates (12.9 vs 16.7 %, p = 0.01), although a greater number of extended resections were performed (23.1 vs. 14.8 %, p < 0.01).

Conclusions: Hospitals with high volumes of lung cancer resections performed surgery with a higher ratio of complex procedures and achieved reduced in-house mortality, fewer complications, and lower failure to rescue rates.
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http://dx.doi.org/10.1016/j.lungcan.2020.08.018DOI Listing
November 2020

Author response to: Comment on: Abdominal fluid samples (negative for SARS-CoV-2) from a critically unwell patient with respiratory COVID-19.

Br J Surg 2020 11 19;107(12):e624. Epub 2020 Sep 19.

Department of General, Visceral, Transplantation, Vascular and Pediatric Surgery, University Hospital Wuerzburg, Oberduerrbacher Str. 6, 97080, Wuerzburg, Germany.

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http://dx.doi.org/10.1002/bjs.11898DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7537022PMC
November 2020

Impact of Borderline Resectability in Pancreatic Head Cancer on Patient Survival: Biology Matters According to the New International Consensus Criteria.

Ann Surg Oncol 2021 Apr 12;28(4):2325-2336. Epub 2020 Sep 12.

Department of General, Visceral, Transplantation, Vascular and Paediatric Surgery, Julius Maximilians University Wuerzburg, Würzburg, Germany.

Background: International consensus criteria (ICC) have redefined borderline resectability for pancreatic ductal adenocarcinoma (PDAC) according to three dimensions: anatomical (BR-A), biological (BR-B), and conditional (BR-C). The present definition acknowledges that resectability is not just about the anatomic relationship between the tumour and vessels but that biological and conditional dimensions also are important.

Methods: Patients' tumours were retrospectively defined borderline resectable according to ICC. The study cohort was grouped into either BR-A or BR-B and compared with patients considered primarily resectable (R). Differences in postoperative complications, pathological reports, overall (OS), and disease-free survival were assessed.

Results: A total of 345 patients underwent resection for PDAC. By applying ICC in routine preoperative assessment, 30 patients were classified as stage BR-A and 62 patients as stage BR-B. In total, 253 patients were considered R. The cohort did not contain BR-C patients. No differences in postoperative complications were detected. Median OS was significantly shorter in BR-A (15 months) and BR-B (12 months) compared with R (20 months) patients (BR-A vs. R: p = 0.09 and BR-B vs. R: p < 0.001). CA19-9, as the determining factor of BR-B patients, turned out to be an independent prognostic risk factor for OS.

Conclusions: Preoperative staging defining surgical resectability in PDAC according to ICC is crucial for patient survival. Patients with PDAC BR-B should be considered for multimodal neoadjuvant therapy even if considered anatomically resectable.
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http://dx.doi.org/10.1245/s10434-020-09100-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940298PMC
April 2021

Colorectal cancer in Crohn's colitis is associated with advanced tumor invasion and a poorer survival compared with ulcerative colitis: a retrospective dual-center study.

Int J Colorectal Dis 2021 Jan 12;36(1):141-150. Epub 2020 Sep 12.

Department of Surgery, Friedrich-Alexander-University Erlangen, Krankenhausstraße 12, 91054, Erlangen, Germany.

Purpose: Colorectal cancer is a well-recognized complication of inflammatory bowel diseases (IBD), such as ulcerative colitis (UC) and Crohn's colitis (CC). In this study, we assess the clinico-pathological features and outcomes of patients with colorectal cancer from UC in comparison with CC.

Methods: Data of all patients with colitis-associated cancer (CAC) who underwent surgery at Erlangen or Würzburg University Clinic between 1995 and 2015 were selected. Clinical, histopathological, and survival data were analyzed retrospectively.

Results: Of all 88 patients with CAC, 20 patients had Crohn's colitis and 68 patients had ulcerative colitis. We observed a young median age at tumor diagnosis (49.5 years UC; 45.5 years CC, p = 0.208) in both diseases and a long median disease duration before CAC (19 years UC; 18 years CC; p = 0.840). Patients with CC suffered more often from rectal cancer (14 (70.0%) in CC; 23 (33.8%) in UC; p = 0.005) and advanced tumor stages (8 (47.0%) pT4 in CC; 14 (25.0%) pT4/ypT4 in UC; p = 0.008). Five-year overall survival rate was 39.3% for CC and 67.1% for UC (p = 0.009 for difference between the groups). Survival did not differ significantly between UC and CC in the multivariate analysis after correction for UICC tumor stage.

Conclusion: CAC in CC showed advanced tumor stages associated with reduced survival compared with CAC in UC. This may be explained by less intense surveillance in patients with CC leading to delayed cancer diagnosis.
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http://dx.doi.org/10.1007/s00384-020-03726-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7782386PMC
January 2021
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