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Pancreatic Neoplasms: HELP
Articles by Jan Schmidt
Based on 12 articles published since 2010
(Why 12 articles?)
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Between 2010 and 2020, Jan Schmidt wrote the following 12 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Review The role of the tumor endothelium in leukocyte recruitment in pancreatic cancer. 2012

Schmidt, Jan / Mocevicius, Paulius / Werner, Jens / Ryschich, Eduard. ·Department of Surgery, University of Heidelberg, Germany. ·Surgery · Pubmed #22770953.

ABSTRACT: BACKGROUND: Although pancreatic cancer tissue frequently induces an immune reaction, immunocompetent cells are not able to eliminate the tumor. One potential cause for this ineffective immune response is that a number of active, tumor-cytotoxic T cells are not able to invade into the tumor. METHODS: A potential barrier for invading leukocytes can be the tumor endothelium, which controls recruitment of leukocytes from circulating blood into the tissue. Although attenuated expression of adhesion molecules on the tumor endothelium has been proposed as a mechanism which suppresses intratumoral leukocyte infiltration, the relevance of adhesion molecules for leukocyte recruitment in tumor tissue is poorly understood. RESULTS: The leukocyte extravasation in normal pancreas during acute pancreatitis follows the "classic" leukocyte recruitment cascade and is controlled by the overexpression of endothelial adhesion molecules, such as selectins, intracellular adhesion molecule-1, and platelet endothelial cell adhesion molecule-1. In contrast to acute inflammation in normal pancreas, leukocyte recruitment in pancreatic cancer is a slow process, which does not show a strong dependence on intracellular adhesion molecule-1. In addition, pancreatic cancer has a high degree of heterogeneity of both immunogenic properties and the distribution of tumor-infiltrating leukocytes, such as CD8(+), CD4(+), or regulatory T cells. CONCLUSION: Additional studies may clarify whether T cell recruitment and their activity in pancreatic cancer can be enhanced by modulation of endothelial adhesion molecules.

2 Clinical Trial Influence of interferon-alpha combined with chemo (radio) therapy on immunological parameters in pancreatic adenocarcinoma. 2014

Karakhanova, Svetlana / Mosl, Beate / Harig, Sabine / von Ahn, Katharina / Fritz, Jasmin / Schmidt, Jan / Jäger, Dirk / Werner, Jens / Bazhin, Alexandr V. ·Department of General Surgery, University Hospital Heidelberg, 69120 Heidelberg, Germany. Svetlana.karakhanova@med.uni-heidelberg.de. · Department of General Surgery, University Hospital Heidelberg, 69120 Heidelberg, Germany. beate.mosl@med.uni-heidelberg.de. · Department of General Surgery, University Hospital Heidelberg, 69120 Heidelberg, Germany. Dirk.Jaeger@med.uni-heidelberg.de. · Department of General Surgery, University Hospital Heidelberg, 69120 Heidelberg, Germany. katharinavonahn@hotmail.com. · Department of General Surgery, University Hospital Heidelberg, 69120 Heidelberg, Germany. jasminfritz@web.de. · Department of General Surgery, University Hospital Heidelberg, 69120 Heidelberg, Germany. Jan.Schmidt@hirslanden.ch. · National Centre for Tumor Disease, University Hospital Heidelberg, 69120 Heidelberg, Germany. Dirk.Jaeger@med.uni-heidelberg.de. · Department of General, Visceral, and Transplant Surgery, Ludwig-Maximilians-University, 81377 Munich, Germany. jens.werner@med.uni-heidelberg.de. · Department of General Surgery, University Hospital Heidelberg, 69120 Heidelberg, Germany. Alexandr.bazhin@med.uni-heidelberg.de. ·Int J Mol Sci · Pubmed #24608924.

ABSTRACT: Prognosis of patients with carcinoma of the exocrine pancreas is particularly poor. A combination of chemotherapy with immunotherapy could be an option for treatment of pancreatic cancer. The aim of this study was to perform an immunomonitoring of 17 patients with pancreatic cancer from the CapRI-2 study, and tumor-bearing mice treated with combination of chemo (radio) therapies with interferon-2α. Low doses of interferon-2α led to a decrease in total leukocyte and an increase in monocyte counts. Furthermore, we observed a positive effect of interferon-2α therapy on the dendritic cells and NK (natural killer) cell activation immediately after the first injection. In addition, we recorded an increased amount of interferon-γ and IL-10 in the serum following the interferon-2α therapy. These data clearly demonstrate that pancreatic carcinoma patients also show an immunomodulatory response to interferon-2α therapy. Analysis of immunosuppressive cells in the Panc02 orthotopic mouse model of pancreatic cancer revealed an accumulation of the myeloid-derived suppressor cells in spleens and tumors of the mice treated with interferon-2α and 5-fluorouracil. The direct effect of the drugs on myeloid-derived suppressor cells was also registered in vitro. These data expose the importance of immunosuppressive mechanisms induced by combined chemo-immunotherapy.

3 Clinical Trial Open-label, multicenter, randomized phase III trial of adjuvant chemoradiation plus interferon Alfa-2b versus fluorouracil and folinic acid for patients with resected pancreatic adenocarcinoma. 2012

Schmidt, Jan / Abel, Ulrich / Debus, Jürgen / Harig, Sabine / Hoffmann, Katrin / Herrmann, Thomas / Bartsch, Detlef / Klein, Justus / Mansmann, Ulrich / Jäger, Dirk / Capussotti, Lorenzo / Kunz, Reiner / Büchler, Markus W. ·Department of Surgery, Ruprecht-Karls-University, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany. ·J Clin Oncol · Pubmed #23008325.

ABSTRACT: PURPOSE: Adjuvant chemotherapy prolongs survival in patients with pancreatic cancer, but its benefit is limited. Long-term survival times of up to 44 months after adjuvant chemoradioimmunotherapy in phase II trials motivated the present study. PATIENTS AND METHODS: Between 2004 and 2007, 132 R0/R1 resected patients received either fluorouracil (FU), cisplatin, and interferon alfa-2b (IFN α-2b) plus radiotherapy followed by two cycles of FU (arm A, n=64) or six cycles of FU monotherapy (arm B, n=68). One hundred ten patients (arm A, n=53; arm B, n=57) received at least one dose of the study medication, and these patients composed the per-protocol (PP) population. Biomarkers were analyzed longitudinally for their predictive value. RESULTS: Median survival for all randomly assigned patients was 26.5 months (95% CI, 21.6 to 39.5 months) in arm A and 28.5 months (95% CI, 20.4 to 38.6 months) in arm B. The hazard ratio was 1.04 (arm A v arm B: 95% CI, 0.66 to 1.53; P=.99). Median survival for the PP population was 32.1 months (95% CI, 22.8 to 42.2 months) in arm A and 28.5 months (95% CI, 19.5 to 38.6 months) in arm B (P=.49). Eighty-five percent of patients in arm A and 16% of patients in arm B experienced grade 3 or 4 toxicity. The quality of life was temporarily negatively affected in arm A. CONCLUSION: The FU, cisplatin, and IFN α-2b plus radiotherapy regimen did not improve the survival compared with FU monotherapy. Given the substantial adverse effects, this treatment can currently not be recommended. Nevertheless, the outcome in both arms represents the best survival, to our knowledge, ever reported for patients with resected pancreatic cancer in randomized controlled trials. Future studies will demonstrate whether immune response to IFN α-2b challenge has a predictive value.

4 Article Prognostic value of site-specific metastases in pancreatic adenocarcinoma: A Surveillance Epidemiology and End Results database analysis. 2017

Oweira, Hani / Petrausch, Ulf / Helbling, Daniel / Schmidt, Jan / Mannhart, Meinrad / Mehrabi, Arianeb / Schöb, Othmar / Giryes, Anwar / Decker, Michael / Abdel-Rahman, Omar. ·Hani Oweira, Anwar Giryes, Omar Abdel-Rahman, Swiss Cancer Institute, 6330 Cham, Switzerland. ·World J Gastroenterol · Pubmed #28348494.

ABSTRACT: AIM: To evaluate the prognostic value of site-specific metastases among patients with metastatic pancreatic carcinoma registered within the Surveillance, Epidemiology and End Results (SEER) database. METHODS: SEER database (2010-2013) has been queried through SEER*Stat program to determine the presentation, treatment outcomes and prognostic outcomes of metastatic pancreatic adenocarcinoma according to the site of metastasis. In this study, metastatic pancreatic adenocarcinoma patients were classified according to the site of metastases (liver, lung, bone, brain and distant lymph nodes). We utilized chi-square test to compare the clinicopathological characteristics among different sites of metastases. We used Kaplan-Meier analysis and log-rank testing for survival comparisons. We employed Cox proportional model to perform multivariate analyses of the patient population; and accordingly hazard ratios with corresponding 95%CI were generated. Statistical significance was considered if a two-tailed RESULTS: A total of 13233 patients with stage IV pancreatic cancer and known sites of distant metastases were identified in the period from 2010-2013 and they were included into the current analysis. Patients with isolated distant nodal involvement or lung metastases have better overall and pancreatic cancer-specific survival compared to patients with isolated liver metastases (for overall survival: lung CONCLUSION: Pancreatic adenocarcinoma patients with isolated liver metastases have worse outcomes compared to patients with isolated lung or distant nodal metastases. Further research is needed to identify the highly selected subset of patients who may benefit from local treatment of the primary tumor and/or metastatic disease.

5 Article 5-Fluorouracil and interferon-α immunochemotherapy enhances immunogenicity of murine pancreatic cancer through upregulation of NKG2D ligands and MHC class I. 2012

Khallouf, Hadeel / Märten, Angela / Serba, Susanne / Teichgräber, Volker / Büchler, Markus W / Jäger, Dirk / Schmidt, Jan. ·University Hospital Heidelberg, AG Jäger, INF 460, 69120 Heidelberg, Germany. khallouf@stud.uni-heidelberg.de ·J Immunother · Pubmed #22421942.

ABSTRACT: Pancreatic cancer has the poorest prognosis of all gastrointestinal cancers, driving the need for new therapeutic approaches. Adjuvant 5-fluorouacil (5-FU) chemotherapy proved effective in increasing the survival of patients with resected tumors. Furthermore, the addition of interferon alpha (IFN-α) immunotherapy to 5-FU has shown encouraging clinical results. The aim of this study was to determine the relevance of different immune cell populations, namely natural killer (NK) cells, CD8 T cells, and dendritic cells, in the anticancer immune response mediated by the combination therapy using an orthotopic mouse model of pancreatic carcinoma and to get more insight into the underlying mechanisms of action. Depleting CD8 T cells, NK cells, or dendritic cells significantly reduced the anticancer effects mediated by the combination therapy. Tumors of mice treated with 5-FU+IFN-α harbored higher numbers of infiltrating NK cells in comparison with control mice. In addition, NK cells isolated from these mice showed enhanced cytotoxicity against Panc02 pancreatic cancer cells. Furthermore, 5-FU+IFN-α treatment increased the expression of major histocompatibility complex class I and NKG2D ligands on Panc02 cells that could be a potential key for enhancing the immunogenicity of tumors. Understanding how this combination therapy enhances the immunogenicity of pancreatic tumors in our model may provide potential predictive biomarkers. This will allow to evaluate the efficacy of this immunochemotherapy more effectively in future clinical trials and to identify patients who will benefit most from it.

6 Article αL β2 integrin is indispensable for CD8+ T-cell recruitment in experimental pancreatic and hepatocellular cancer. 2012

Takeichi, Takayuki / Mocevicius, Paulius / Deduchovas, Olegas / Salnikova, Olga / Castro-Santa, Edward / Büchler, Markus W / Schmidt, Jan / Ryschich, Eduard. ·Department of Surgery, University of Heidelberg, Heidelberg, Germany. ·Int J Cancer · Pubmed #21647874.

ABSTRACT: Recruitment of activated leukocytes from peripheral blood into the tumor tissue is a crucial step of the immune response, which is controlled by the interaction between specific adhesion molecules such as endothelial ICAM-1 and leukocyte β(2) -integrins. Although attenuated expression of adhesion molecules on tumor endothelium has been proposed to represent a mechanism, which suppresses the intratumoral leukocyte infiltration, the relevance of adhesion molecules for leukocyte recruitment in tumor tissue is poorly understood. The present study is the first investigation of the role of ICAM-1 and β(2) -integrins in leukocyte recruitment in pancreatic and hepatocellular cancer in vivo, which was studied using knockout mice, intravital time-lapse microscopy and immunohistochemistry. We found that tumor tissue of both pancreatic and hepatocellular cancer was infiltrated with numerous active lymphoid and myeloid leukocytes, although the leukocyte extravasation rate in tumor blood vessels was very low. The knockout of LFA-1 (also known as α(L) β(2) integrin) strongly suppressed recruitment of CD8(+) T cells whereas no significant differences of leukocyte adhesion and infiltration were found in ICAM-1(-/-) and Mac-1(-/-) mice. Analysis of the interstitial leukocyte migration demonstrated that intratumoral leukocytes used haptokinetic type of migration, however, no significant differences of leukocyte migration between any knockout strains were found. We concluded that leukocyte recruitment in pancreatic and hepatocellular cancer is a slow-going process whose dynamics clearly contrasts to a high-speed leukocyte recruitment during acute inflammation. In contrast to acute inflammatory reaction, only LFA-1 controls recruitment of CD8(+) T-cells in both pancreatic and hepatocellular cancer, whereas ICAM-1 and Mac-1 are dispensable.

7 Article Covered stents used for late, postpancreatectomy hemorrhage in the common hepatic artery. 2011

Kolokotronis, Theodoros / Hosch, Waldemar / Schmidt, Jan / Radeleff, Boris / Werner, Jens / Weitz, Jürgen / Büchler, Markus. ·Chirurgische Universitätsklinik, Münster, Germany. theodoros.kolokotronis@uni-muenster.de ·Am Surg · Pubmed #21337890.

ABSTRACT: -- No abstract --

8 Article The need for extended intensive care after pancreaticoduodenectomy for pancreatic ductal adenocarcinoma. 2011

Welsch, Thilo / Degrate, Luca / Zschäbitz, Stefanie / Hofer, Stefan / Werner, Jens / Schmidt, Jan. ·Department of General, Visceral and Transplant Surgery, University of Heidelberg, Im Neuenheimer Feld 110, Heidelberg, Germany. ·Langenbecks Arch Surg · Pubmed #20336311.

ABSTRACT: PURPOSE: Pancreaticoduodenectomy (PD) is standard for patients with resectable pancreatic ductal adenocarcinoma (PDAC) in the pancreatic head, neck, and uncinate process, but it is associated with a relatively high morbidity. This study aimed to identify risk factors for extended postoperative intensive care unit (ICU) admission and assess the impact of ICU treatment on patient survival. METHODS: Between October 2001 and June 2008, patients that underwent PD for PDAC in the pancreatic head were identified from a prospective database. Patients admitted to the ICU after an initial recovery period were compared to those not admitted regarding comorbidities, intraoperative parameters, resection size, and tumor biology. RESULTS: Five hundred and forty patients were included. Of these, 17.8% required extended postoperative ICU admission (immediate, 9.3%; delayed, 7.6%). Immediate ICU admission was most frequently required for increased intraoperative blood loss and fluid management. Delayed ICU treatment was most frequently required for hemorrhage, respiratory insufficiency, or pancreatic fistula. Morbidity and 30-day mortality rates were 54.2% and 2.6%, respectively. ICU admission correlated with significantly lower survival rates compared to no ICU admission (P = 0.0155). Multivariate risk factors for ICU admission included a history of diabetes mellitus and heart failure (NYHA I-III), an intraoperative blood transfusion, and a longer operating time. CONCLUSIONS: The need for extended ICU admission is associated with higher in-hospital mortality and reduced long-term outcome. The highest mortality was observed after delayed ICU admission. Preoperative diabetes, heart failure and long operations, and intraoperative blood transfusions substantially increased the risk for ICU requirement.

9 Article Expression of A disintegrin and metalloprotease 10 in pancreatic carcinoma. 2010

Gaida, Matthias M / Haag, Natascha / Günther, Frank / Tschaharganeh, Darjus F / Schirmacher, Peter / Friess, Helmut / Giese, Nathalia A / Schmidt, Jan / Wente, Moritz N. ·Institute of Pathology, University of Heidelberg, Heidelberg, Germany. ·Int J Mol Med · Pubmed #20596609.

ABSTRACT: The protease ADAM10 influences progression and metastasis of cancer cells and is overexpressed in various malignancies. Therefore, the aim of our study was to evaluate the expression and potential function of ADAM10 in the pathophysiology of pancreatic cancer (PDAC). ADAM10 expression in normal pancreatic (NP), chronic pancreatitis (CP), PDAC tissues, as well as PDAC cell lines was determined. To evaluate whether rhADAM10 or ADAM10 silencing influences cancer cell viability, MTT assay was used. Matrigel invasion and wound healing assays were performed to observe influence on invasion and migration. ADAM10 mRNA was expressed in all samples of NP, CP and PDAC tissue and cell lines. Western blotting and immunohistochemistry revealed stronger ADAM10 expression in PDAC than in NP. ADAM10 silencing or rhADAM10 had no effect on cell viability. ADAM10 silencing markedly reduced invasiveness and migration of cancer cells. These findings establish ADAM10 as a contributing factor in PDAC invasion and metastasis.

10 Article Uncinate process first--a novel approach for pancreatic head resection. 2010

Hackert, Thilo / Werner, Jens / Weitz, Jürgen / Schmidt, Jan / Büchler, Markus W. ·Department of Surgery, University of Heidelberg, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany. ·Langenbecks Arch Surg · Pubmed #20582600.

ABSTRACT: PURPOSE: Partial pancreatico-duodenectomy is the standard treatment for malignancies of the pancreatic head. We describe a technical modification with a retrograde dissection of the pancreatic head as a novel surgical approach. METHODS: Retrograde resection of the pancreatic head is performed starting with the uncinate process after division of the first jejunal loop and transection of the pancreas as the last operative step of the resection. Technical aspects and possible advantages for this procedure are discussed. RESULTS: The retrograde resection can be safely performed and offers a comfortable and innovative approach for pancreatico-duodenectomy. CONCLUSIONS: The "uncinate process first" approach can serve as an additional approach in modern pancreatic surgery. Further studies are required to evaluate this procedure regarding operative parameters and postoperative outcome compared to the standard resection.

11 Article Eps8 is recruited to lysosomes and subjected to chaperone-mediated autophagy in cancer cells. 2010

Welsch, Thilo / Younsi, Alexander / Disanza, Andrea / Rodriguez, Jose Antonio / Cuervo, Ana Maria / Scita, Giorgio / Schmidt, Jan. ·Department of General, Visceral and Transplant Surgery, University of Heidelberg, Im Neuenheimer Feld 110, Heidelberg, Germany. thilo.welsch@med.uni-heidelberg.de ·Exp Cell Res · Pubmed #20184880.

ABSTRACT: Eps8 controls actin dynamics directly through its barbed end capping and actin-bundling activity, and indirectly by regulating Rac-activation when engaged into a trimeric complex with Eps8-Abi1-Sos1. Recently, Eps8 has been associated with promotion of various solid malignancies, but neither its mechanisms of action nor its regulation in cancer cells have been elucidated. Here, we report a novel association of Eps8 with the late endosomal/lysosomal compartment, which is independent from actin polymerization and specifically occurs in cancer cells. Endogenous Eps8 localized to large vesicular lysosomal structures in metastatic pancreatic cancer cell lines, such as AsPC-1 and Capan-1 that display high Eps8 levels. Additionally, ectopic expression of Eps8 increased the size of lysosomes. Structure-function analysis revealed that the region encompassing the amino acids 184-535 of Eps8 was sufficient to mediate lysosomal recruitment. Notably, this fragment harbors two KFERQ-like motifs required for chaperone-mediated autophagy (CMA). Furthermore, Eps8 co-immunoprecipitated with Hsc70 and LAMP-2, which are key elements for the CMA degradative pathway. Consistently, in vitro, a significant fraction of Eps8 bound to (11.9+/-5.1%) and was incorporated into (5.3+/-6.5%) lysosomes. Additionally, Eps8 binding to lysosomes was competed by other known CMA-substrates. Fluorescence recovery after photobleaching revealed that Eps8 recruitment to the lysosomal membrane was highly dynamic. Collectively, these results indicate that Eps8 in certain human cancer cells specifically localizes to lysosomes, and is directed to CMA. These results open a new field for the investigation of how Eps8 is regulated and contributes to tumor promotion in human cancers.

12 Article Soluble iC3b as an early marker for pancreatic adenocarcinoma is superior to CA19.9 and radiology. 2010

Märten, Angela / Büchler, Markus W / Werft, Wiebke / Wente, Moritz N / Kirschfink, Michael / Schmidt, Jan. ·Department of Surgery, University of Heidelberg, Heidelberg 69120, Germany. angela.maerten@med.uni-heidelberg.de ·J Immunother · Pubmed #20139773.

ABSTRACT: Pancreatic adenocarcinoma as an aggressive tumor still lacks specific markers. Resection offers the only potential cure, and earlier diagnosis could benefit many patients. Here, we analyzed siC3b as a potential diagnostic marker. Soluble iC3b is generated in the fluid phase after binding of autoantibodies to tumor cells and subsequent inactivation of the complement cascade by interaction with complement regulatory proteins. Two hundred thirty-two plasma samples from patients with adjuvant treatment after resection, from healthy volunteers, and from vulnerable patients were collected prospectively and analyzed for siC3b. Every 3 months, the patients underwent imaging and the results from siC3b enzyme-linked immunosorbent assay were categorized according to radiologically defined recurrence within 4 months after blood withdrawal. Furthermore, the regulatory factors of the complement system were analyzed in tumor cells and in urine. The most important finding was that up to 4 months before radiologically defined recurrence, siC3b plasma level is increased with a sensitivity and specificity resulting in an area under the curve of 0.85, which could be further increased by combining it with CA19.9 (area under the curve=0.92). Complement regulatory proteins are highly expressed in pancreatic carcinoma cells and detectable in the patient's urine. In summary, screening for siC3b in patients with an increased risk for pancreatic ductal adenocarcinoma (patients with chronic pancreatitis, hereditary pancreatitis, after curative resection, and patients with a variety of familial cancer syndromes) allows for early detection with high sensitivity, as siC3b plasma levels are increased up to 4 months before radiologic evidence. Sensitivity could be further increased by combining this approach with CA19.9.