Marko Kornmann

Universität Ulm, Ulm, Baden-Württemberg, Germany

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Publications (131)464.57 Total impact

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    ABSTRACT: A condylomata acuminata infection is caused by human papillomaviridae (HPV). This sexually transmitted condition most often affects the perineal region. Importantly, infections with types 16 and 18 are associated with an increased risk for anal and cervix cancer. In most cases topical therapy is sufficient for successfully treating condylomata acuminata. Here, we report the case of a 51-year old patient who suffered from a giant perianal located condylomata acuminata which had developed over a period of more than 10 years. Imaging by MRI revealed a possible infiltration of the musculus sphincter ani externus. Because a topical treatment or a radiotherapy was considered unfeasible, a surgical treatment was the only therapeutic option in this unusual case. First, a colostomy was performed and subsequently a resection of the tumor in toto with circular resection of the external portion of the musculus sphincter ani externus was performed. The large skin defect was closed by two gluteus flaps. The rectum wall was reinserted in the remnant of the musculus sphincter ani externus. Postoperatively, parts of the flaps developed necrosis. Therefore, a vacuum sealing therapy was initiated. Subsequently, the remaining skin defects were closed by autologous skin transplantation. Six months later the colostomy could be reversed. To date, one year after first surgery, the patient has still a normal sphincter function and no recurrence of the condylomata acuminata. This case report demonstrates how giant condylomata acuminata can be successfully treated by extended surgical procedures including colostomy and plastic reconstruction of resulting defects upon resection.
    No preview · Article · Jan 2016
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    ABSTRACT: Pancreatic tumors comprise benign lesion and malignant lesion, most importantly pancreatic adenocarcinoma, acinar cell carcinoma, neuroendocrine carcinoma or metastasis. Surgical resection provides the only chance for cure for malignant pancreatic tumors. In some cases, surgical resection is performed because a malignant lesion is suspected, however, histopathological examinations eventually reveal a benign lesion. Here, we report the case of a 49-year-old woman, who was initially diagnosed with a neuroendocrine tumor of the pancreas with metastasis to the liver. The patient underwent distal pancreatectomy and atypical liver resection. Surprisingly, however, histopathological examination revealed an intrapancreatic accessory spleen (IPAS) of the pancreatic tail as well as liver hemangioma. This unique case report highlights the impact of extensive preoperative examinations to differentiate benign and malignant pancreatic lesions and, possibly, prevent patients from unnecessary surgery.
    No preview · Article · Nov 2015 · International Journal of Surgery Case Reports
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    ABSTRACT: Purpose To establish a chordoma tissue cohort (n = 43) and to correlate localization, size, metastasis, residual disease (R-status), recurrences, histological subtype, matrix content, and Ki-67 proliferation index with patients’ overall survival (OS). Methods and results We used routine histopathology supplemented by immunohistochemistry. In our patient cohort (median age 69 years, range 17 to 84 years) the median OS was 8.25 years. 24 chordomas were localized in the sacrum, 6 in lumbar vertebrae, 7 in thoracic and cervical vertebrae, 5 were limited to the clivus, and one was localized in the nasal septum. Ten patients had metastases, with pulmonary, nodal, and hepatic involvement. 23 patients had recurrent disease. 23 chordomas were classified as ‘not otherwise specified’ (NOS). Besides NOS, we found the following differentiation patterns: renal cell cancer like in six cases, chondroid in four cases, hepatoid differentiation in three cases, and anaplastic morphology in six cases. Ki-67 index of ≥10 %, presence of metastasis, and the low content of extracellular matrix were statistically linked to poor OS (p < 0.05). The matrix-poor phenotype had a higher Ki-67 index (p < 0.05). Furthermore, presence of metastasis was associated with a higher Ki-67 index in the primary lesion, a positive resection margin, and multiple recurrences (p < 0.05 each). Conclusion We propose to include these parameters in the final pathologic report of the resected chordoma.
    No preview · Article · Sep 2015 · European Spine Journal
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    ABSTRACT: Chordomas are tumors which arise at vertebral bodies and the base of the skull. Although rare in incidence they are deadly owing to slow growth and a lack of effective therapeutic options. In this study, we addressed the need for chordoma cell systems that can be used to identify therapeutic targets and empower testing of candidate pharmacological drugs. Eight human chordoma cell lines that we established exhibited cytology, genomics, mRNA and protein profiles that were characteristic of primary chordomas. Candidate responder profiles were identified through an immunohistochemical analysis of a chordoma tissue bank of 43 patients. Genomic, mRNA and protein expression analyses confirmed that the new cell systems were highly representative of chordoma tissues. Notably, all cells exhibited a loss of CDKN2A and p16 resulting in universal activation of the CDK4/6 and Rb pathways. Therefore, we investigated the CDK4/6 pathway and responses to the CDK4/6-specific inhibitor palbociclib. In the newly validated system, palbociclib treatment efficiently inhibited tumor cell growth in vitro and a drug responder vs non-responder molecular signature was defined based on immunohistochemical expression of CDK4/6/pRb (S780). Overall, our work offers a valuable new tool for chordoma studies including the development. Copyright © 2015, American Association for Cancer Research.
    Full-text · Article · Jul 2015 · Cancer Research
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    ABSTRACT: Aim: Adjuvant treatment is still controversially discussed for elderly colon cancer (CC) patients. Our aim was to investigate the benefit of adjuvant treatment for younger (<70 years) and elderly (≥70 years) patients. Patients and Methods: The long-term outcome of patients (n=855) enrolled in a randomized controlled trial comparing adjuvant chemotherapy with 5-FU alone, 5-FU plus folinic acid (FA), and 5-FU plus interferon-alpha (IFNa) was compared in younger (<70 years) and elderly (≥70 years) patients using a quotient of each patient's survival time and his expected residual life expectancy (QSL) and a multivariate Cox proportional hazards model. Results: Eightyear overall survival (OS) rates were 58.3% and 57.4% for younger (n=653) and elderly (n=202) patients, respectively. In elderly patients, 8-year OS rates were 51.4%, 61.8%, and 56.3, and median QSL scores were 0.338, 0.371, and 0.343 for 5-FU (n=59), 5-FU plus FA (n=76), and 5-FU plus IFNa (n=67), respectively. In elderly patients treatment with 5-FU plus FA decreased the risk for an event by 1.5-fold compared to 5-FU (HR=0.657, 95%CI=0.495-0.870, p=0.004) and 5- FU plus INFa (HR=0.685, 95%CI=0.515-0.912, p=0.009). Conclusion: Our analysis clearly demonstrates for the first time an additional benefit of FA for adjuvant treatment of elderly CC patients. We conclude that this regimen is very safe and effective for adjuvant treatment of elderly patients.
    No preview · Article · Jul 2015 · Anticancer research
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    ABSTRACT: With an increasing number of cancer survivors quality of life (QoL) becomes more and more important in the treatment of rectal cancer (RC). QoL after sphincter-preserving anterior resection (AR), however, was found nonsuperior to abdominoperineal resection. The aim of our study was to evaluate QoL after AR compared with colon cancer patients after right hemicolectomy (CC) and healthy lay persons without history of cancer (HL) in long-term follow-up. Consecutive alive RC patients (n = 293) who received an AR between 1998 and 2008 were included. CC patients (n = 201) and HL of the same age were used as a surgical and a nonsurgical control group, respectively. QoL was assessed using European Organization of Research and Treatment of Cancer questionnaires QLQ-C 30 and -CR 38. Questionnaires from 116 RC patients, 105 CC patients, and 103 HL were evaluable with a median time after surgery of 5 years. The global health status did not differ. Social functioning, future perspectives, and financial difficulties tended to poorer scores in the cancer groups. Physical functioning was better in RC and CC patients compared with HL. Defecation problems and diarrhea were more frequent in RC patients (P < .05). An additional open question revealed a median stool frequency of 3, 2, and 1 per day for RC, CC, and HL, respectively. Defecation problems were more frequent in RC patients who received radiation therapy (P < .05). Diarrhea and defecation problems impaired QoL after AR for RC, which was worsened after radiation therapy. To improve QoL of RC patients in the future, physicians have to focus on minimization of gastrointestinal side effects while optimizing surgical reconstruction. Copyright © 2015 Elsevier Inc. All rights reserved.
    No preview · Article · Jun 2015 · Clinical Colorectal Cancer
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    ABSTRACT: A 60-year-old patient presented with a solitary mass within the right hepatic lobe. Diagnostic imaging revealed a solid tumor on the diameter of 3 cm. In absence of any extrahepatic manifestation and based on FNAC findings the lesion was classisfied a primary hepatic chondroid sarcoma. However, after right hemihepatectomy histologic assessment resulted the final diagnosis of a benign chondroid hamartoma. Our findings add another variant to the versatile phenotype of liver hamartoma.
    No preview · Article · Dec 2014
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    ABSTRACT: Colorectal cancer (CRC) is the fourth leading cause of cancer related death worldwide due to high apoptotic resistance and metastatic potential. Since mutations as well as deregulation of CK1 isoforms contribute to tumor development and tumor progression, CK1 has become an interesting drug target. In this study we show that CK1 isoforms are differently expressed in colon tumor cell lines and that growth of these cell lines can be inhibited by CK1-specific inhibitors. Furthermore, expression of CK1δ and ε is changed in colorectal tumors compared to normal bowel epithelium, and high CK1ε expression levels significantly correlate with prolonged patients’ survival. In addition to changes in CK1δ and ε expression, mutations within exon 3 of CK1δ were detected in colorectal tumors. These mutations influence ATP binding resulting in changes in kinetic parameters of CK1δ. Overexpression of these mutants in HT29 cells alters their ability to grow anchorage independently. Consistent with these results, these CK1δ mutants lead to differences in proliferation rate and tumor size in xenografts due to changes in gene expression, especially in genes involved in regulation of cell proliferation, cell cycle, and apoptosis. In summary, our results provide evidence that changes in the expression levels of CK1 isoforms in colorectal tumors correlate with patients’ survival. Furthermore, CK1 mutants affect growth and proliferation of tumor cells and induce tumor growth in xenografts, leading to the assumption that CK1 isoforms provide interesting targets for the development of novel effective therapeutic concepts to treat colorectal cancer. This article is protected by copyright. All rights reserved.
    No preview · Article · Nov 2014 · International Journal of Cancer
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    ABSTRACT: Introduction: The Peutz-Jeghers syndrome (PJS) is a rare hereditary, autosomal-dominant disorder. It is characterized by a gastrointestinal polyposis and mucocutaneous melanic spots. It has also been reported as a precondition for malignancies with a life-time-hazard for cancer up to 93%, caused by a germline mutation in the STK11 gene. Presentation of case: A 21-year-old man presented with nausea and abdominal pain. He had a known history of PJS since the age of 13 when he was treated for intussusception due to a hamartomatous polyp. Preoperative diagnostics revealed a second intussusception and an extensive intestinal polyposis. Intraoperative findings confirmed the suspected diagnoses and desvagination was performed. Nearly 50 polyps were removed from the small intestinum over several longitudinal sections. As the appendix appeared thickened an appendectomy was performed simultaneously. Histology showed hamartomatous polyps and the incidental finding of a pT1 carcinoid of the appendix. The patient recovered well and needed no further treatment for his carcinoid tumor. Discussion: The mechanism of carcinogenesis in PJS still remains debatable, although the genetic disorder underlying the syndrome is known. A predisposition for carcinoid tumors also stays questionable. To our knowledge there is no description of an association between carcinoid tumors of the appendix and PJS to date. Conclusion: Life-expectancy in patients with PJS is reduced. Causes are the development of malignancies and complications from the polyps such as intussusception. Since there is no treatment possible main focus must be aimed at early recognition of malignancies and the prevention of complications.
    Preview · Article · Oct 2014 · International Journal of Surgery Case Reports
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    ABSTRACT: Background Unlike metastatic colorectal cancer (CRC) there are to date few reports concerning the predictive value of molecular biomarkers on the clinical outcome in stage II/III CRC patients receiving adjuvant chemotherapy. Aim of this study was to assess the predictive value of proteins related with the EGFR- and VEGFR- signalling cascades in these patients.Methods The patients' data examined in this study were from the collective of the 5-FU/FA versus 5-FU/FA/irinotecan phase III FOGT-4 trial. Tumor tissues were stained by immunohistochemistry for VEGF-C, VEGF-D, VEGFR-3, Hif-1 ¿, PTEN, AREG and EREG expression and evaluated by two independent, blinded investigators.Survival analyses were calculated for all patients receiving adjuvant chemotherapy in relation to expression of all makers above.ResultsPatients with negative AREG and EREG expression on their tumor had a significant longer DFS in comparison to AREG/EREG positive ones (p< 0.05). The benefit on DFS in AREG-/EREG- patients was even stronger in the group that received 5-FU/FA/irinotecan as adjuvant treatment (p=0.002). Patients with strong expression of PTEN profited more in terms of OS under adjuvant treatment containing irinotecan (p< 0.05). Regarding markers of the VEGFR- pathway we found no correlation of VEGF-C- and VEGFR-3 expression with clinical outcome. Patients with negative VEGF-D expression had a trend to live longer when treated with 5-FU/FA (p=0.106). Patients who were negative for Hif-1 ¿, were disease-free in more than 50% at the end of the study and showed significant longer DFS-rates than those positive for Hif-1 ¿ (p=0.007). This benefit was even stronger at the group treated with 5-FU/FA/irinotecan (p=0.026). Finally, AREG-/EREG-/PTEN+ patients showed a trend to live longer under combined treatment combination.Conclusions The addition of irinotecan to adjuvant treatment with 5-FU/FA does not provide OS or DFS benefit in patients with stage II/III CRC. Nevertheless, AREG/EREG negative, PTEN positive and Hif-1 ¿ negative patients might profit significantly in terms of DFS from a treatment containing fluoropyrimidines and irinotecan. Our results suggest a predictive value of these biomarkers concerning adjuvant chemotherapy with 5-FU/FA +/¿ irinotecan in stage II/III colorectal cancer.
    Full-text · Article · Oct 2014 · Journal of Experimental & Clinical Cancer Research
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    ABSTRACT: About 10% of all cancer patients will develop brain metastases during advanced disease progression. Interestingly, the vast majority of brain metastases occur in only three types of cancer: Melanoma, lung and breast cancer. In this review, we focus on summarizing the prognosis and impact of surgical resection of brain metastases originating from gastrointestinal cancers such as esophageal, gastric, pancreatic and colorectal cancer. The incidence of brain metastases is <1% in pancreatic and gastric cancer and <4% in esophageal and colorectal cancer. Overall, prognosis of these patients is very poor with a median survival in the range of only months. Interestingly, a substantial number of patients who had received surgical resection of brain metastases showed prolonged survival. However, it should be taken into account that all these studies were not randomized and it is likely that patients selected for surgical treatment presented with other important prognostic factors such as solitary brain metastases and exclusion of extra-cranial disease. Nevertheless, other reports have demonstrated long-term survival of patients upon resection of brain metastases originating from gastrointestinal cancers. Thus, it appears to be justified to consider aggressive surgical approaches for these patients.
    Full-text · Article · Sep 2014 · International Journal of Molecular Sciences

  • No preview · Article · Aug 2014 · Zeitschrift für Gastroenterologie
  • Xiaoran Liu · Xiaodong Tian · Feng Wang · Yongsu Ma · Marko Kornmann · Yinmo Yang
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    ABSTRACT: Gemcitabine is a standard chemotherapeutic agent for locally advanced and metastatic pancreatic cancer. However, the chemoresistance of pancreatic cancer is the major barrier to efficient chemotherapy. Here, we reported that BRG1, a chromatin modulator, was exclusively overexpressed in human pancreatic ductal adenocarcinoma tissues. BRG1 knockdown inhibited PANC-1 and MIA PaCa-2 cell growth in vitro and in vivo, reduced the phosphorylation/activation of Akt and p21(cip/waf), enhanced intrinsic and gemcitabine induced apoptosis and attenuated gemcitabine-induced downregulation of E-cadherin. Moreover, by establishing acquired chemoresistance of MIA PaCa-2 cells in vitro, we found that BRG1 knockdown effectively reversed the chemoresistance to gemcitabine. Surprisingly, inhibiting Akt phosphorylation resulted in BRG1 suppression in pancreatic cancer cells, indicating BRG1 as a new downstream target of Akt signalling. Taken together, our findings suggest that BRG1 promotes both intrinsic and acquired chemoresistance of pancreatic cancer cells, and BRG1 crosstalks with Akt signalling to form a positive feedback loop to promote pancreatic cancer development.
    No preview · Article · Jun 2014 · European journal of cancer (Oxford, England: 1990)
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    ABSTRACT: Aim: We analyzed survival of patients diagnosed with ampullary cancer (AC) and pancreatic ductal adenocarcinomas (PDAC). Patients and methods: Between 1996 and 2009, 505 and 69 patients diagnosed with PDAC and AC, respectively, were identified. Overall survival was analyzed according to tumor entity, therapeutic approach and pathological tumor stage. Results: The 5-year overall survival rate of patients with AC (37%; 95% confidence interval 25-49%) was remarkably higher compared to PDAC patients (7%; 95% confidence interval 5-10%). In both cohorts, surgical resection improved survival. Analysis of pathological factors revealed a survival benefit for patients staged with small primary tumors (pT1/2) and exclusion of distant metastases (M0) for both PDAC and AC. Interestingly, absence of lymph node metastasis substantially improved survival in AC, but not in PDAC. Conclusion: Overall survival of patients with AC is superior compared to that of patients with PDAC. Therapeutically, adequate regional lymph node dissection seems particularly important for the surgical management of AC.
    No preview · Article · Jun 2014 · Anticancer research

  • No preview · Article · May 2014 · Gastroenterology
  • Marko Kornmann · Karl-Heinrich Link · Andrea Formentini

    No preview · Article · Feb 2014
  • Xiaoran Liu · Xiaodong Tian · Feng Wang · Yongsu Ma · Marko Kornmann · Yinmo Yang
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    ABSTRACT: Gemcitabine is a standard chemotherapeutic agent for locally advanced and metastatic pancreatic cancer. However, the chemoresistance of pancreatic cancer is the major barrier to efficient chemotherapy. Here, we reported that BRG1, a chromatin modulator, was exclusively overexpressed in human pancreatic ductal adenocarcinoma tissues. BRG1 knockdown inhibited PANC-1 and MIA PaCa-2 cell growth in vitro and in vivo, reduced the phosphorylation/activation of Akt and p21cip/waf, enhanced intrinsic and gemcitabine induced apoptosis and attenuated gemcitabine-induced downregulation of E-cadherin. Moreover, by establishing acquired chemoresistance of MIA PaCa-2 cells in vitro, we found that BRG1 knockdown effectively reversed the chemoresistance to gemcitabine. Surprisingly, inhibiting Akt phosphorylation resulted in BRG1 suppression in pancreatic cancer cells, indicating BRG1 as a new downstream target of Akt signalling. Taken together, our findings suggest that BRG1 promotes both intrinsic and acquired chemoresistance of pancreatic cancer cells, and BRG1 crosstalks with Akt signalling to form a positive feedback loop to promote pancreatic cancer development.
    No preview · Article · Jan 2014
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    ABSTRACT: Evading apoptosis is a hallmark of pancreatic cancer. In pancreatic cancer models, chemotherapy down-regulates the antiapoptotic protein cellular FLICE inhibitory protein (c-FLIP), which renders cells sensitive to apoptosis. Currently, the relevance of c-FLIP expression as a biomarker in pancreatic cancer is unknown, and here we assessed the prognostic significance of the c-FLIP expression status in a large cohort of pancreatic cancer patients with clinical follow-up. Cellular FLICE inhibitory protein expression levels were determined by immunohistochemistry in 120 surgically resected ductal pancreatic adenocarcinomas. Survival analysis by c-FLIP status was compared with established clinicopathologic biomarkers as well as Ki-67 and cyclooxygenase 2 expression levels as 2 other established independent prognostic biomarkers in pancreatic cancer. Of 120 tumors, 111 (91%) were c-FLIP positive, whereas 9 (9%) were completely c-FLIP negative. Cyclooxygenase 2 was positive in 59 cases (52%), and Ki-67 was positive in more than 10% of tumor cells in 51 cases (44%). Univariate and multivariate survival analysis (correcting for stage, grade, and proliferation index) showed that c-FLIP is an independent prognostic factor. Specifically, c-FLIP negativity identifies 9% of patients with a highly aggressive disease course (P = 0.0001). Cellular FLICE inhibitory protein expression status is a valuable prognostic biomarker in pancreatic cancer.
    No preview · Article · Sep 2013 · Pancreas
  • S Hofmann · Tfe Barth · M Kornmann · D Henne-Bruns

    No preview · Article · Jul 2013 · Zeitschrift für Gastroenterologie
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    ABSTRACT: Our aim was to determine predictive factors for the diagnosis and postoperative complications of acute appendicitis. Data sets of 1,439 consecutive adults and children who had an appendectomy between 1999 and 2008 were retrospectively analyzed. A mild acute appendicitis was present in 50 % (n = 722) and a severe acute appendicitis in 25 % (n = 355) of the patients. No signs of any pathology were found in 6 % (n = 82). Gender, white blood count (WBC), C-reactive protein (CRP), and ultrasound (US) examination were important indicators of mild acute and severe acute appendicitis in adults and children. Postoperative complications occurred in 16 % (237/1,439), mainly consisting of wound infections (8 %, n = 122) and bowel dysfunction (5 %, n = 76). Sixty-two patients (4.3 %) required reoperations. One patient died (1/1,439, 0.07 % mortality rate). Age, pathology, and the presence of bacteria in the intraoperative swab were important predictive factors for postoperative complications in adults and children. Time since onset of symptoms and type of operation were also associated with postoperative complications among adults. Complications developed in 21 and 9 % of the adults (155/754 and 10/125) who had open and laparoscopic surgery, respectively. Besides history and clinical examination, WBC, CRP, and US examination remain important factors for diagnosing acute appendicitis. Complications are related to the pathology, presence of bacteria, and type of operation. Early diagnosis within 48 h may be important. A laparoscopic procedure in adults may also cause fewer wound infections.
    No preview · Article · Jul 2013 · Langenbeck s Archives of Surgery

Publication Stats

3k Citations
464.57 Total Impact Points

Institutions

  • 1996-2015
    • Universität Ulm
      • • Clinic of General and Visceral Surgery
      • • Institute of General Medicine
      Ulm, Baden-Württemberg, Germany
  • 2009
    • Asklepios Paulinen Klinik Wiesbaden
      Wiesbaden, Hesse, Germany
  • 2006
    • Peking University
      Peping, Beijing, China
  • 1996-2000
    • University of California, Irvine
      • • Department of Biological Chemistry
      • • Department of Medicine
      Irvine, California, United States
  • 1999
    • University of Southern California
      Los Ángeles, California, United States