Publications by authors named "Marius Kemper"

9 Publications

  • Page 1 of 1

Integrin alpha-V is an important driver in pancreatic adenocarcinoma progression.

J Exp Clin Cancer Res 2021 Jun 26;40(1):214. Epub 2021 Jun 26.

Institute of Anatomy and Experimental Morphology, University Medical-Center Hamburg-Eppendorf, Hamburg, Germany.

Background: Mesothelial E- and P-selectins substantially mediate the intraperitoneal spread of Pancreatic ductal adenocarcinoma (PDA) cells in xenograft models. In the absence of selectins in the host, the integrin subunit alpha-V (ITGAV, CD51) was upregulated in the remaining metastatic deposits. Here we present the first experimental study to investigate if ITGAV plays a functional role in PDA tumor growth and progression with a particular focus on intraperitoneal carcinomatosis.

Methods: Knockdown of ITGAV was generated using an RNA interference-mediated approach in two PDA cell lines. Tumor growth, intraperitoneal and distant metastasis were analyzed in a xenograft model. Cell lines were characterized in vitro. Gene expression of the xenograft tumors was analyzed. Patient samples were histologically classified and associations to survival were evaluated.

Results: The knockdown of ITGAV in PDA cells strongly reduces primary tumor growth, peritoneal carcinomatosis and spontaneous pulmonary metastasis. ITGAV activates latent TGF-β and thereby drives epithelial-mesenchymal transition. Combined depletion of ITGAV on the tumor cells and E- and P-selectins in the tumor-host synergistically almost abolishes intraperitoneal spread. Accordingly, high expression of ITGAV in PDA cells was associated with reduced survival in patients.

Conclusion: Combined depletion of ITGAV in PDA cells and E- and P-selectins in host mice massively suppresses intraperitoneal carcinomatosis of PDA cells xenografted into immunodeficient mice, confirming the hypothesis of a partly redundant adhesion cascade of metastasizing cancer cells. Our data strongly encourage developing novel therapeutic approaches for the combined targeting of E- and P-selectins and ITGAV in PDA.
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http://dx.doi.org/10.1186/s13046-021-01946-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8235815PMC
June 2021

Are muscle parameters obtained by computed tomography associated with outcome after esophagectomy for cancer?

Clin Nutr 2021 Jun 1;40(6):3729-3740. Epub 2021 May 1.

Department of Intensive Care Medicine, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.

Background & Aims: Esophageal cancer patients often suffer from cancer-related malnutrition and, as a result, sarcopenia. Whether sarcopenia worsens the outcome after esophagectomy is unclear. Inconsistent study results are partly caused by varying cut-off values used for defining sarcopenia. To overcome this challenge, a new statistical approach is proposed in this study: analyzing the linear association of computer tomography derived muscle parameters with important clinical short- and long-term outcomes post esophagectomy, regardless of cut-offs.

Methods: Skeletal muscle index (SMI), quantifying muscle mass, was assessed with computed tomography (CT) in 98 patients undergoing esophagectomy. Muscle radiation attenuation (MRA) was measured to evaluate muscle quality. To evaluate the influence of the SMI and MRA on post-surgery complications, logistic regression models were used. To analyze the relationship of lengths of stay to muscle parameters, the competing risk approach introduced by Fine and Gray was applied. For survival analysis, log-rank test and Cox proportional hazards regression modeling were used.

Results: Neither a relevant association of SMI nor MRA with pneumonia and esophagoenteric leak were observed. Furthermore, no relevant association to lengths of stay in intensive care or hospital were detected. If the SMI increased, the odds for pleural effusion and pleural empyema decreased, but the odds of a pulmonary embolism increased. Univariate, unadjusted long-term survival analysis revealed that lower MRA and lower SMI were associated with shorter survival (P = 0.03). However, if the analysis was adjusted for confounders, e.g., Charlson Comorbidity Index, no relevant association regarding long-term survival was detected.

Conclusion: Consequently, poor muscle status, determined by CT imaging, does not justify denying a patient an oncologic resection. The Charlson Comorbidity Index, however, was superior for preoperative risk stratification.
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http://dx.doi.org/10.1016/j.clnu.2021.04.040DOI Listing
June 2021

Liver surgery-specific complications are an independent factor influencing long-term survival following major hepatectomy.

HPB (Oxford) 2021 Mar 30. Epub 2021 Mar 30.

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

Background: A severity grading system for liver surgery-specific complications, given the acronym FABIB, has been standardized to increase the feasibility and comparability of academic reports in liver surgery. Whether the FABIB score is associated with long-term survival following major hepatectomy has not been previously investigated.

Methods: 297 consecutive patients who had undergone major hepatectomy between 2012 and 2019 were recruited. The postoperative complications were documented according to the FABIB system and, for comparison purposes, Clavien-Dindo classification. Their influence on 90-day mortality and long-term survival was analyzed retrospectively.

Results: Taking the relevant confounders into account, the FABIB score was a robust factor associated with long-term survival after major hepatectomy: patients with high FABIB scores (≥6) had a 2.415-fold higher risk of death compared to patients with low FABIB scores (≤2) (P = 0.002). In contrast to that, the Clavien-Dindo Classification (grade III + IV vs. grade I + II) was not associated with survival in our cohort (P = 0.873).

Conclusion: Liver surgery-specific complications, measured by the FABIB system, impact long-term survival after major hepatectomy independent of relevant confounders. We propose the FABIB score as a composite endpoint for randomized controlled trials and a quality assessment tool in liver surgery.
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http://dx.doi.org/10.1016/j.hpb.2021.02.013DOI Listing
March 2021

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

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

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

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

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

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

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

Clinical Significance of Circulating Tumor Cells in Gastrointestinal Carcinomas.

Diagnostics (Basel) 2020 Mar 30;10(4). Epub 2020 Mar 30.

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

The idea of a liquid biopsy to screen, surveil and treat cancer patients is an intensively discussed and highly awaited tool in the field of oncology. Despite intensive research in this field, the clinical application has not been implemented yet and further research has to be conducted. However, one component of the liquid biopsy is circulating tumor cells (CTCs) whose potential for clinical application is evaluated in the following. CTCs can shed from primary tumors to the peripheral blood at any time point during the progress of a malignant disease. Following, one single CTC can be the origin for distant metastasis at later cancer stage. Thus, CTCs have great potential to either be used in cancer diagnostics and patient stratification or to function as a target for new therapeutic approaches to stop tumor dissemination and metastasis at the very early beginning. Due to the biological fundamental role of CTCs in tumor progression, here, we provide an overview of CTCs in gastrointestinal cancers and their potential use in the clinical setting. In particular, we discuss the usage of CTC for screening and stratifying patients' risk. Moreover, we will discuss the potential role of CTCs for treatment specification and treatment monitoring.
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http://dx.doi.org/10.3390/diagnostics10040192DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7235836PMC
March 2020

Serum Midkine is a clinical significant biomarker for colorectal cancer and associated with poor survival.

Cancer Med 2020 03 26;9(6):2010-2018. Epub 2020 Jan 26.

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

Colorectal carcinoma (CRC) is one of the most common carcinomas worldwide. Early detection is crucial for reducing morbidity and mortality. Several promising studies described the use of midkine (MK) as a tumor marker. This study aimed to investigate a larger collective to ascertain if the preoperative serum midkine level (S-MK) is suitable as a marker for screening and if S-MK correlates with tumor progression and localization. It was also investigated for the first time whether patients with high S-MK show poor survival. This prospective single-center study included 299 patients with CRC. The preoperative serum midkine level (S-MK) was determined using ELISA. Established tumor markers Carcinoembryonic antigen (CEA) and Carbohydrate antigen 19-9 (CA 19-9) were collected for comparison. The median follow-up period was 65 months. S-MK was significantly elevated in patients with CRC (P < .001). The receiver operation characteristic (ROC) curve has an area under the curve (AUC) of 0.868 (P < .001). A cut-off value of 56.42 pg/mL results in a sensitivity of 84.3% and a specificity of 75.4%. In the one-way analysis of variance (ANOVA), there were no significant correlations between S-MK and tumor progression, localization. Furthermore, no significant correlation to CEA und CA 19-9 could be found. Kaplan-Meier survival analysis was able to show for the first time that patients with S-MK of more than 225 pg/mL have a significantly shorter survival. Multivariate Cox regression showed that only CEA was an independent prognostic factor for survival. S-MK helps estimate the prognosis for CRC and is a valuable component for developing a multimarker panel for screening and surveillance.
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http://dx.doi.org/10.1002/cam4.2884DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7064087PMC
March 2020

Increase of CD45-positive Immune Cells in Liver Parenchyma Indicates a More Favorable Prognosis for Patients With Barrett's Cancer.

Anticancer Res 2019 Mar;39(3):1191-1196

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

Background: Despite advances in perioperative management, the 5-year survival rate of patients with esophageal adenocarcinoma (Barrett's cancer) is poor. Adjuvant immunotherapies are currently the subject of clinical trials. The prognostic role of tumor-infiltrating T-lymphocytes (TILs) expressing CD45 has only been investigated in primary tumors. The significance of TILs in the target organs of distant metastases, in particular the liver, is unclear. This study examined the influence of CD45-positive cells in liver parenchyma and primary tumors on cumulative survival.

Materials And Methods: The density of CD45-positive cells was analyzed immunohistochemically using tissue microarrays. Sixty-five patients for whom a liver biopsy was available in addition to the primary tumor were included in the study. Liver metastases were found in 21 patients. The results of the immunohistochemical analysis were correlated with patient's outcomes. The Cox proportional hazard model was used to compute mortality hazard ratio in consideration of clinical variables.

Results: Elevated density of CD45-positive cells in the liver biopsy corresponded with a better cumulative survival rate (p<0.001), while no significant differences were found for primary tumors. Multivariate Cox regression analysis showed that a high density of CD45-positive cells in the liver parenchyma was an independent prognostic parameter of longer overall survival (hazard ratio(HR)=0.432, p=0.048).

Conclusion: The density of CD45-positive cells in the liver parenchyma is an easily measured prognostic biomarker that can identify patient subgroups with a better prognosis. In addition, the density of CD45-positive cells in the liver may assist as a criterion for selecting patients with a high potential for response to adjuvant immunotherapy.
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http://dx.doi.org/10.21873/anticanres.13229DOI Listing
March 2019

Surgical Treatment of Chronic Pancreatitis: The State of the Art.

Chirurgia (Bucur) 2018 May-Jun;113(3):300-306

Chronic pancreatitis is a common disease accompanied with considerable morbidity and mortality. Complications associated with chronic pancreatitis, such as pseudocysts, stenosis of adjacent anatomic structures or pain that cannot be managed conservatively, may be treatable surgically or interventionally by endoscopy. Surgery is superior to endoscopy in regard to long-term pain management. Duodenum preserving pancreatic resection is the surgical procedure of choice in patients with inflamed changes of the head of the pancreas. The best timing of surgery, the ideal standardized perioperative management are the focus of current research.
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http://dx.doi.org/10.21614/chirurgia.113.3.300DOI Listing
September 2018

Is hyaluronan deposition in the stroma of pancreatic ductal adenocarcinoma of prognostic significance?

PLoS One 2017 5;12(6):e0178703. Epub 2017 Jun 5.

Centre of Experimental Medicine, Department of Anatomy and Experimental Morphology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.

Background: Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis and the number of PDAC-related deaths is rising. Recently the tumour stroma and in particular one of its main components, hyaluronan (HA), have attracted considerable attention as intravenous hyaluronidase treatment together with conventional chemotherapy considerably prolonged survival in HA-rich PDA patients. We therefore wanted to investigate the prognostic significance of HA deposition in PDA using both antibodies to HA and hyaluronan binding protein (HABP).

Material And Methods: Tissue microarrays of PDAs of 184 patients and pancreatic xenografts tumours were immunohistochemically (IHC) stained for HA using either biotinylated hyaluronic acid binding protein (HABP) or anti-HA antibody.

Results: The pattern of staining with HABP differed significantly from that with antibody IHC. Antibody staining was found both within cancer cells and in the extracellular matrix and staining could not be eliminated by hyaluronidase predigestion of the tissue sections. In contrast, HABP staining was generally confined to the extracellular matrix and was completely abolished by hyaluronidase pretreatment. HA positivity as determined by HABP was associated with larger primary tumours (p = 0.046). There were no correlations between overall survival, disease-free survival and HA expression.

Conclusion: Presence of HA alone is not of prognostic importance in PDAC, and IHC with utilization of antibody detection shows no reliable staining pattern and should not be applied for HA IHC.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0178703PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5459453PMC
September 2017
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