Cord Langner

Medical University of Graz, Gratz, Styria, Austria

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Publications (323)1108.61 Total impact

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    ABSTRACT: Purpose Tumor grade is a traditional prognostic parameter in colorectal cancer. Remarkably, however, there is still no generally accepted consensus how to perform tumor grading. In this study, we systematically compared the prognostic value of traditional grading based upon histological features, that is, gland formation alone with grading based upon both histological and cytological features, such as nuclear pleomorphism and anaplasia (“alternative grade”). Methods Three hundred eighty-one tumors of randomly selected patients were retrospectively reviewed. Traditional and alternative tumor grades were related to various clinicopathological features and to progression-free and cancer-specific survival applying both univariate and multivariate testing. Results Traditional and alternative tumor grades were significantly associated with T and N classification, tumor size, lymphovascular invasion, as well as both progression-free and cancer-specific survival. In Cox’s proportional hazards regression models, the alternative grade was superior to the traditional tumor grade and was significantly associated with progression-free survival (hazard ratio 1.57, 95 % confidence interval 1.04–2.35; p = 0.031), independent of patients’ age and gender, T and N classification, and lymphovascular invasion. Likewise, patients with tumors with high alternative grade were more likely to die of disease (hazard ratio 1.30, 95 % confidence interval 0.85–2.00), but this difference was not statistically significant (p = 0.22). Conclusions Tumor grade based upon both histological and cytological features was superior to grade based upon histological features alone and proved to be an independent prognostic parameter. Thus, tumor grade based upon both histological and cytological features may help to improve prognostic stratification and may thereby affect clinical decision-making and patient management.
    No preview · Article · Jan 2016 · International Journal of Colorectal Disease
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    ABSTRACT: Background: Tumour budding is an adverse prognostic indicator in colorectal cancer (CRC). Marked overall peritumoural inflammation has been associated with favourable outcome and may lead to the presence of isolated cancer cells due to destruction of invading cancer cell islets. Methods: We assessed the prognostic significance of tumour budding and peritumoural inflammation in a cohort of 381 patients with CRC applying univariate and multivariate analyses. Results: Patients with high-grade budding and marked inflammation had a significantly better outcome compared with patients with high-grade budding and only mild inflammation. Outcome in these cases, however, was still worse compared with cases with low-grade budding, in which the extent of peritumoural inflammation had no further prognostic effect. Conclusions: Tumour budding proved to be a powerful prognostic variable in patients with CRC. Scattering of invading cancer cell islets by marked overall peritumoural inflammation seems to have a minor role.British Journal of Cancer advance online publication, 14 January 2016; doi:10.1038/bjc.2015.454 www.bjcancer.com.
    No preview · Article · Jan 2016 · British Journal of Cancer
  • Nicole Max · Franz Siebert · Cord Langner

    No preview · Article · Dec 2015 · Endoscopy
  • Lisa Setaffy · Cord Langner
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    ABSTRACT: Although often viewed as a single disease, colorectal cancer more accurately represents a constellation of heterogeneous subtypes that result from different combinations of genetic events and epigenetic alterations. Chromosomal instability (CIN), microsatellite instability (MSI) and CpG island methylator phenotype (CIMP) have been identified as the three major molecular characteristics, which interact with other significant mutations, such as mutations in the KRAS and BRAF genes. High-level MSI (MSI-H) is of eminent clinical importance. It is the seminal molecular feature for the identification of individuals with Lynch syndrome, but it may also occur in sporadic cancers with CIMP phenotype, which arise from serrated precursor lesions. MSI-H status is a marker of favorable prognosis and may be used for outcome prediction, that is, molecular grading. Among others, mucinous and medullary histology, signet-ring cell differentiation, and a marked anti-tumoral immune response are histological features suggesting MSI. Universal tumor testing is recommended and may be performed using immunohistochemistry (mismatch repair protein expression) or molecular analysis, as has recently been recommended by an international task force. In this review, we consider in detail the molecular pathogenesis of colorectal cancer, focusing on the diagnosis of MSI in both hereditary and sporadic tumors. © 2015, Versalius University Medical Publisher. All rights reserved.
    No preview · Article · Nov 2015 · Polish journal of pathology: official journal of the Polish Society of Pathologists
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    ABSTRACT: Aims: Medullary carcinoma of the large bowel mainly occurs right-sided in elderly females. The tumour is almost invariably microsatellite instable and has been associated with favourable outcome. Our study aimed to present three cases of medullary carcinoma originating from the small bowel. Methods and results: We describe three cases of small bowel medullary carcinoma. Two patients had celiac disease, diagnosed at the age of 79 and 71 years, respectively. The tumours showed the characteristic syncytial growth pattern with marked intratumoural lymphocytic inflammation. Loss of MLH1 (and PMS2) expression was observed in all cases, consistent with high-level microsatellite instability. All tumours were negative for Epstein-Barr virus. Follow-up information was available for one patient, who is recurrence-free six years after resection. Discussion: Medullary carcinoma of the small bowel is exceedingly rare. Our data and a review of the literature suggest that this tumour type is characteristic for celiac disease and may be the histological type underlying small bowel cancers with high-level microsatellite instability in patients with celiac disease. This article is protected by copyright. All rights reserved.
    No preview · Article · Nov 2015 · Histopathology
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    ABSTRACT: Tuberous sclerosis complex (TSC) is a genetic disorder with multisystem involvement that is due to autosomal-dominantly inherited or sporadic mutations in TSC1 and TSC2 genes. Involvement of the gastrointestinal tract is rare. We report the case of a 51-year-old woman with diagnosis of TSC established by genetic testing, who presented with colorectal hamartomatous polyposis. Multiple small polyps were found scattered through the left colon and rectum. Histology revealed a distinct spindle cell proliferation in the lamina propria, originating from the muscularis mucosae. The cells lacked atypia or mitotic activity and were diffusely positive for smooth muscle actin and negative for S100 protein. Genetic testing proved a disease causing frameshift mutation in the TSC1 gene. Although gastrointestinal involvement is rare in TSC, hamartomatous polyps can be the initial manifestation of this syndrome. Genetic testing should be considered in every case for which TSC is clinically suspected.
    No preview · Article · Oct 2015 · Pathology - Research and Practice
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    ABSTRACT: This Guideline is an official statement of the European Society of Gastrointestinal Endoscopy (ESGE). The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system 1 2 was adopted to define the strength of recommendations and the quality of evidence. Main recommendations 1 ESGE recommends endoscopic en bloc resection for superficial esophageal squamous cell cancers (SCCs), excluding those with obvious submucosal involvement (strong recommendation, moderate quality evidence). Endoscopic mucosal resection (EMR) may be considered in such lesions when they are smaller than 10 mm if en bloc resection can be assured. However, ESGE recommends endoscopic submucosal dissection (ESD) as the first option, mainly to provide an en bloc resection with accurate pathology staging and to avoid missing important histological features (strong recommendation, moderate quality evidence). 2 ESGE recommends endoscopic resection with a curative intent for visible lesions in Barrett's esophagus (strong recommendation, moderate quality evidence). ESD has not been shown to be superior to EMR for excision of mucosal cancer, and for that reason EMR should be preferred. ESD may be considered in selected cases, such as lesions larger than 15 mm, poorly lifting tumors, and lesions at risk for submucosal invasion (strong recommendation, moderate quality evidence). 3 ESGE recommends endoscopic resection for the treatment of gastric superficial neoplastic lesions that possess a very low risk of lymph node metastasis (strong recommendation, high quality evidence). EMR is an acceptable option for lesions smaller than 10 - 15 mm with a very low probability of advanced histology (Paris 0-IIa). However, ESGE recommends ESD as treatment of choice for most gastric superficial neoplastic lesions (strong recommendation, moderate quality evidence). 4 ESGE states that the majority of colonic and rectal superficial lesions can be effectively removed in a curative way by standard polypectomy and/or by EMR (strong recommendation, moderate quality evidence). ESD can be considered for removal of colonic and rectal lesions with high suspicion of limited submucosal invasion that is based on two main criteria of depressed morphology and irregular or nongranular surface pattern, particularly if the lesions are larger than 20 mm; or ESD can be considered for colorectal lesions that otherwise cannot be optimally and radically removed by snare-based techniques (strong recommendation, moderate quality evidence). © Georg Thieme Verlag KG Stuttgart · New York.
    Full-text · Article · Sep 2015 · Endoscopy
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    ABSTRACT: This study aimed to assess the clinicopathological significance of tumour differentiation of metastatic lymph node tissue in patients with American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) stage III colorectal cancer. In a cohort of 145 patients, lymph node grades were G1 in 77 (53.1%), G2 in 41 (28.3%) and G3 in 27 (18.6%) cases, respectively. Despite differences in 77 (53.1%) cases, primary tumour and lymph node grade correlated significantly (Somer's D=0.639; p<0.001). Lymph node grade was significantly associated with N classification (p=0.009), tumour size (p=0.024) and lymphovascular invasion (p=0.004). Patients with lymph node grade G1 had better progression-free survival (p=0.031) and cancer-specific survival (p=0.008). Multivariable analysis identified lymph node grade as independent predictor of cancer-specific survival in this cohort. In conclusion, lymph node grade emerged as a promising novel prognostic variable for patients with AJCC/UICC stage III disease. Additional studies are warranted to validate this new finding.
    No preview · Article · Jun 2015 · Journal of Clinical Pathology
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    ABSTRACT: We investigated the hypothesis that the varying treatment efficacy of adjuvant 5-fluorouracil (5FU) in stage III colon cancer is linked to the TP53 mutational status. ABCSG-90 was a prospective randomized trial in which effect of adjuvant 5FU was studied in stage III colon cancer patients. Tumor material of 70% of these patients (389/572) was available for analysis of the biomarker TP53 using a TP53-gene-specific Sanger sequencing protocol. Median follow-up was 88 months. TP53 mutation frequency was 33%. A significant interaction between TP53 status, outcomes and nodal category was found (P = 0.0095). In the N1 category, TP53 wildtype patients had significantly better overall survival than TP53 mutated (81.0% vs. 62.0% overall survival at 5 years; HR = 2.131; 95% CI: 1.344–3.378; P = 0.0010). In the N2 category, the TP53 status did not affect survival (P = 0.4992). In TP53 wildtype patients, the prognostic significance of N category was significantly enhanced (P = 0.0002). In TP53 mutated patients, survival curves of N1 and N2 patients overlapped and nodal category was no longer prognostic. The biomarker TP53 independently predicted effect of adjuvant 5FU in N1 colon cancer patients. TP53 was not predictive in N2 patients, in whom 5FU is known to have no effect.
    Full-text · Article · Jun 2015 · EBioMedicine
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    ABSTRACT: This study aimed to assess the clinicopathological significance of tumour differentiation of metastatic lymph node tissue in patients with American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) stage III colorectal cancer. In a cohort of 145 patients, lymph node grades were G1 in 77 (53.1%), G2 in 41 (28.3%) and G3 in 27 (18.6%) cases, respectively. Despite differences in 77 (53.1%) cases, primary tumour and lymph node grade correlated significantly (Somer's D=0.639; p<0.001). Lymph node grade was significantly associated with N classification (p=0.009), tumour size (p=0.024) and lymphovascular invasion (p=0.004). Patients with lymph node grade G1 had better progression-free survival (p=0.031) and cancer-specific survival (p=0.008). Multivariable analysis identified lymph node grade as independent predictor of cancer-specific survival in this cohort. In conclusion, lymph node grade emerged as a promising novel prognostic variable for patients with AJCC/UICC stage III disease. Additional studies are warranted to validate this new finding. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
    No preview · Conference Paper · May 2015
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    Preview · Article · Mar 2015 · Journal of Crohn s and Colitis
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    ABSTRACT: HintergrundDas Management von „kleinen Polypen“ im distalen Kolon und Rektum ist in den Fokus der Kosten-Nutzen-Analyse der Vorsorgekoloskopie geraten. So wird insbesondere im angloamerikanischen Sprachraum aktuell diskutiert, winzige (Die Amerikanische Gesellschaft für Gastroenterologische Endoskopie (ASGE) hat im Rahmen ihrer sog. Innovationsdiskussion („Preservation and Incorporation of Valuable Endoscopic Innovations [PIVI]“) diskutiert, Polypen unter 0,5 cm Durchmesser zwar zu entfernen, nicht jedoch histopathologisch zu untersuchen - um angeblich Kosten zu sparen (www. http://www.asge.org/publications/). In Computermodellrechnungen wurde ermittelt, dass durch das „Entfernen und Verwerfen“ pro Vorsorgekoloskopie 25 US-Dollar gespart werden könnten [1, 2].Nicht nur aus berufspolitischen Gründen wird die Diskussion auch in Deutschland geführt - und von einigen be ...
    No preview · Article · Mar 2015 · Der Pathologe
  • Annika Resch · Nora I Schneider · Cord Langner
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    ABSTRACT: Surgical resection is the treatment of choice for patients with locally confined disease, but early cancers may be adequately treated by endoscopic resection alone. In advanced colorectal cancers, accurate staging including pathological lymph node assessment is crucial for patient counselling and decision making. In addition to the extent of surgical lymph node removal and the thoroughness of the pathologist in dissecting the cancer specimen lymph node recovery is related to the actual number of regional lymph nodes that is related to patient demographics, tumor location and biology. Current guidelines recommend a minimum of twelve nodes harvested as the standard of care. In patients with node-negative tumors a variety of histological features may be used for adjusted risk assessment, including histological subtyping, lymphatic and venous invasion, tumor budding and tumor necrosis as well as the anti-tumor host inflammatory response which has been identified as favorable feature in several studies. In rectal cancer, involvement of the circumferential resection margin and the plane of surgery are important prognostic factors. Early or superficial colorectal cancer is defined as invasive adenocarcinoma invading into, but not beyond the submucosa. A number of features require special attention because they are used to determine the necessity for radical surgery. In addition to the assessment of completeness of excision, these include the recording of parameters that predict the presence of lymph node metastasis, namely the depth of invasion into the submucosa, tumor grade, and the presence of additional risk factors, such as angioinvasion and tumor budding. The combination of these parameters allows the stratification of affected individuals into low-risk and high-risk categories.Keywords: colorectal cancer - early colorectal cancer - lymph node metastasis - pathological features - risk factors - prognosis.
    No preview · Article · Feb 2015 · Ceskoslovenska patologie

  • No preview · Article · Jan 2015 · Zeitschrift für Gastroenterologie
  • Cord Langner · Michael Vieth
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    ABSTRACT: This chapter explains the terminology and classification of colorectal neoplastic precursor lesions, with focus on serrated lesions: hyperplastic polyp, sessile serrated adenoma/polyp (or lesion), mixed polyp and traditional serrated adenoma. We refer to practical issues, such as the measurement of polyp size and the grading of intraepithelial neoplasia/dysplasia (low grade vs. high grade). The definition of invasion is driven by the World Health Organization and defined as invasion into the submucosal layer. Risk assessment of pT1 colorectal cancers is the prerequisite of clinical decision making ranging from follow-up only to additional endoscopic and surgical procedures. The evaluation is based upon the following parameters: depth of invasion (for sessile lesions reported according to Kikuchi levels sm1–sm3; for polypoid/pedunculated lesions reported according to Haggitt levels I–IV), tumour grade, vascular invasion, margin involvement, budding (tumour cell dissociation at the invasion front) and (possibly) perineural invasion.
    No preview · Chapter · Jan 2015
  • Cord Langner
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    ABSTRACT: Although often viewed as a single disease, colorectal cancer more accurately represents a family of diseases with different precursor lesions. Conventional (tubular, tubulovillous and villous) adenomas are the most common neoplastic lesions occurring in the large intestine. They have adenomatous polyposis coli (APC) mutations and arise from dysplastic aberrant crypt foci, initially as polyclonal lesions. In sporadic tumours, neoplastic progression follows the traditional pathway (chromosomal instability pathway), resulting in CpG island methylator phenotype (CIMP)-negative, microsatellite-stable (MSS), BRAF and KRAS wild-type cancers. Germline mutations in the APC gene lead to familial adenomatous polyposis. Conventional adenomas are also the precursors of Lynch syndrome-associated microsatellite-instable (MSI-high) cancers. Sessile serrated adenoma/polyp (SSA/P) is the principal precursor lesion of the serrated pathway, in which BRAF mutation can lead to colorectal cancer with MSI-high CIMP-high or MSS CIMP-high phenotype. SSA/Ps have been associated with synchronous and metachronous invasive adenocarcinomas as well as so-called interval carcinomas. Serrated polyposis is rare but most likely underdiagnosed. Affected individuals bear an increased but unspecified risk for the development of colorectal cancer; close endoscopic surveillance is warranted. Traditional serrated adenomas (TSAs) are much less common than the other serrated lesions. Cancers originating from TSAs may show KRAS mutation with a CIMP-high MSS phenotype. © 2014 S. Karger AG, Basel.
    No preview · Article · Jan 2015 · Digestive Diseases
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    Nora I Schneider · Cord Langner

    Preview · Article · Jan 2015
  • Annika Resch · Cord Langner
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    ABSTRACT: The pathological examination of early colorectal cancer specimens, in particular 'malignant polyps', provides important prognostic information. The depth of invasion into the submucosal layer assessed according to the Haggitt (for pedunculated lesions) or Kikuchi (for nonpolypoid lesions) classification systems or by direct measurement has been associated with the risk of lymph node metastasis. Angioinvasion, in particular lymphatic invasion, budding, tumor differentiation or grade, and resection margin status have been identified as further risk factors. The combination of these parameters allows the stratification of affected individuals into low- and high-risk categories, which is pivotal for clinical management. For low-risk cancers, defined as a completely excised Haggitt level 1-3/Kikuchi sm1 tumor with no evidence of poor differentiation or angioinvasion, local excision is generally regarded as adequate treatment. Oncological surgical resection is, however, indicated for high-risk cancers, which show at least one of the following features: Haggitt level 4/Kikuchi sm3 invasion, the presence of lymphatic (or vascular) invasion, poor differentiation, or positive resection margin. The inclusion of molecular markers such as tumor suppressor genes and their products, markers involved in tumor vascularization, and markers related to tumor cell adhesion and invasion may help to refine risk stratification, but data on molecular markers are still limited in this regard. © 2014 S. Karger AG, Basel.
    No preview · Article · Jan 2015 · Digestive Diseases
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    ABSTRACT: Intrahepatic granuloma formation and fibrosis characterize the pathological features of Schistosoma mansoni (S.m.) infection. Based on previously observed substantial anti-fibrotic effects of 24-nor-ursodeoxycholic acid (norUDCA) in Abcb4/Mdr2(-/-)mice with cholestatic liver injury and biliary fibrosis, we hypothesized that norUDCA improves inflammation-driven liver fibrosis in S.m. infection. Adult NMRI mice were infected with 50 S.m. cercariae and after 12 weeks received either norUDCA- or ursodeoxycholic acid (UDCA)-enriched diet (0.5% wt/wt) for 4 weeks. Bile acid effects on liver histology, serum biochemistry, key regulatory cytokines, hepatic hydroxyproline content as well as granuloma formation were compared to naive mice and infected controls. In addition, effects of norUDCA on, primary T-cell activation/proliferation and maturation of the antigen-presenting-cells (dendritic cells, macrophages) were determined in vitro. UDCA as well as norUDCA attenuated the inflammatory response in livers of S.m. infected mice but exclusively norUDCA changed cellular composition and reduced size and of hepatic granulomas as well as TH2-mediated hepatic fibrosis in vivo. Moreover norUDCA affected surface expression level of major histocompatibility complex (MHC) class II of macrophages and dendritic cells as well as activation/proliferation of T-lymphocytes in vitro, whereas UDCA had no effect. This study demonstrates pronounced anti-inflammatory and anti-fibrotic effects of norUDCA compared to UDCA in S.m. induced liver injury and indicates that norUDCA directly represses antigen presentation of antigen presenting cells and subsequent T-cell activation in vitro. Therefore norUDCA represents a promising drug for the treatment of this important cause of liver fibrosis. Copyright © 2014. Published by Elsevier B.V.
    Full-text · Article · Nov 2014 · Journal of Hepatology
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    ABSTRACT: The International Consultations on Urological Diseases are international consensus meetings, supported by the World Health Organization and the Union Internationale Contre le Cancer, which have occurred since 1981. Each consultation has the goal of convening experts to review data and provide evidence-based recommendations to improve practice. In 2012, the selected subject was bladder cancer, a disease which remains a major public health problem with little improvement in many years. The proceedings of the 2nd International Consultation on Bladder Cancer, which included a 'Pathology of Bladder Cancer Work Group,' have recently been published; herein, we provide a summary of developments and consensus relevant to the practicing pathologist. Although the published proceedings have tackled a comprehensive set of issues regarding the pathology of bladder cancer, this update summarizes the recommendations regarding selected issues for the practicing pathologist. These include guidelines for classification and grading of urothelial neoplasia, with particular emphasis on the approach to inverted lesions, the handling of incipient papillary lesions frequently seen during surveillance of bladder cancer patients, descriptions of newer variants, and terminology for urine cytology reporting.Modern Pathology advance online publication, 21 November 2014; doi:10.1038/modpathol.2014.158.
    No preview · Article · Nov 2014 · Modern Pathology

Publication Stats

4k Citations
1,108.61 Total Impact Points

Institutions

  • 2004-2015
    • Medical University of Graz
      • Institute of Pathology
      Gratz, Styria, Austria
  • 2013
    • Klinikum Bayreuth GmbH
      Bayreuth, Bavaria, Germany
  • 2001-2012
    • Karl-Franzens-Universität Graz
      • Institute of Psychology
      Gratz, Styria, Austria
  • 2006-2011
    • IST Austria
      Klosterneuberg, Lower Austria, Austria
  • 2010
    • Ruhr-Universität Bochum
      • Institut für Pathologie
      Bochum, North Rhine-Westphalia, Germany
    • University of Bayreuth
      Bayreuth, Bavaria, Germany
  • 2009
    • Universität Heidelberg
      • Department of Urology
      Heidelburg, Baden-Württemberg, Germany
    • University of Rostock
      • Institut für Pathologie
      Rostock, Mecklenburg-Vorpommern, Germany
  • 2008
    • Keio University
      Edo, Tōkyō, Japan
  • 2000-2001
    • Klinikum Kassel
      Cassel, Hesse, Germany
  • 1999
    • Philipps University of Marburg
      • Institut für Physiologie und Pathophysiologie
      Marburg, Hesse, Germany