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8. Circulating levels of soluble urokinase plasminogen activator receptor predict outcome after resection of biliary tract cancer

Author

Loosen, Sven H., Breuer, Annemarie, Tacke, Frank, Kather, Jakob N., Gorgulho, Joao, Alizai, Patrick H., Bednarsch, Jan, Roeth, Anjali A., Lurje, Georg, Schmitz, Sophia M., Brozat, Jonathan F., Paffenholz, Pia, Vucur, Mihael, Ritz, Thomas, Koch, Alexander, Trautwein, Christian, Ulmer, Tom F., Roderburg, Christoph, Longerich, Thomas, Neumann, Ulf P., and Luedde, Tom

Published
2020
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13. Quality of Life, Sarcopenia and Nutritional Status in Patients with Esophagogastric Tumors before and after Neoadjuvant Therapy.

Author

Schooren, Lena, Oberhoff, Grace H., Koch, Alexander, Kroh, Andreas, Ulmer, Tom F., Vondran, Florian, Bednarsch, Jan, Neumann, Ulf P., Schmitz, Sophia M., and Alizai, Patrick H.

Subjects
STOMACH tumors, SKELETAL muscle, RESEARCH funding, QUESTIONNAIRES, COMPUTED tomography, ESOPHAGEAL tumors, ADJUVANT chemotherapy, COMBINED modality therapy, QUALITY of life, NUTRITIONAL status, SARCOPENIA
Abstract

Simple Summary: Aside from a decreased quality of life, patients with esophagogastric tumors often suffer from difficulties with eating that impact nutritional status. Both the presence of cancer and the impacted nutritional status can also reduce muscle mass. All of this can impact treatment decisions: a patient with low muscle mass and low caloric impact might have a lower tolerance for chemotherapy or other treatment courses. However, treating physicians do not always have immediate access to current data on muscle mass and nutritional status. If there was a correlation between quality of life and these parameters, this might allow for the estimation of real-time muscle mass and suggest further controlled studies. (1) Background: Health-related quality of life (HRQoL) gains importance as novel treatment options for individuals with esophagogastric tumors to improve long-term survival. Impaired HRQoL has been shown to be a predictor of overall survival. Sarcopenia is a known prognostic factor for postoperative complications. As the regular control of sarcopenia through CT scans might not always be possible and HRQoL and nutritional scores are easier to obtain, this study aimed to assess the relationship between nutritional scores, HRQoL and skeletal muscle mass in patients undergoing chemotherapy for cancers of the upper gastrointestinal tract. (2) Methods: Eighty patients presenting with tumors of the upper GI tract were included and asked to fill out the standardized HRQoL questionnaire, EORTC's QLQ-C30. Nutritional status was assessed using the MNA, MUST and NRS 2002 scores. Sarcopenia was determined semi-automatically based on the skeletal muscle index at the L3 vertebrae level in staging CT scans. (3) Results: In chemo-naïve patients, HRQoL summary scores correlated significantly with nutritional scores and SMI. SMI and HRQoL prior to neoadjuvant therapy correlated significantly with SMI after treatment. (4) Conclusions: HRQoL is a helpful tool for assessing patients' overall constitution. The correlation of HRQoL summary scores and SMI might allow for a rough assessment of skeletal muscle status through HRQoL assessment in chemo-naïve patients. [ABSTRACT FROM AUTHOR]

Published
2024
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14. Insulin Resistance Is the Main Characteristic of Metabolically Unhealthy Obesity (MUO) Associated with NASH in Patients Undergoing Bariatric Surgery

Author

Schmitz, Sophia M., primary, Storms, Sebastian, additional, Koch, Alexander, additional, Stier, Christine, additional, Kroh, Andreas, additional, Rheinwalt, Karl P., additional, Schipper, Sandra, additional, Hamesch, Karim, additional, Ulmer, Tom F., additional, Neumann, Ulf P., additional, and Alizai, Patrick H., additional

Published
2023
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15. Golgi Protein 73 (GP73) Serum Levels Predict Outcome after Resection of Biliary Tract Cancer

Author

Loosen, Sven H., primary, Halpaap, Justus, additional, Labuhn, Simon, additional, Bednarsch, Jan, additional, Alizai, Patrick H., additional, Roeth, Anjali A., additional, Lang, Sven A., additional, Vucur, Mihael, additional, Kather, Jakob N., additional, Knoefel, Wolfram T., additional, Ulmer, Tom F., additional, Neumann, Ulf P., additional, Roderburg, Christoph, additional, and Luedde, Tom, additional

Published
2022
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18. Comparative Analysis of Circulating Biomarkers for Patients Undergoing Resection of Colorectal Liver Metastases

Author

Loosen, Sven H., Roderburg, Christoph, Alizai, Patrick H., Roeth, Anjali A., Schmitz, Sophia M., Vucur, Mihael, Luedde, Mark, Schöler, David, Paffenholz, Pia, Tacke, Frank, Trautwein, Christian, Luedde, Tom, Neumann, Ulf P., and Ulmer, Tom F.

Subjects
Medicine (General), R5-920, CEA, endocrine system diseases, liver resection, CRLM, cancer, CA19-9, CRP, survival, digestive system diseases, Article, CRC
Abstract

Diagnostics : open access journal 11(11), 1999 (2021). doi:10.3390/diagnostics11111999 special issue: "Special issue "Novel approaches in the diagnosis of primary and secondary disease within colorectal cancer" / special issue editors: Lucía Inglada-Pérez, guest editor; José Perea, guest editor", Published by MDPI, Basel

Published
2021
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21. Levels of Circulating PD-L1 Are Decreased in Patients with Resectable Cholangiocarcinoma

Author

Roderburg, Christoph, Loosen, Sven H., Bednarsch, Jan, Alizai, Patrick H., Roeth, Anjali A., Schmitz, Sophia M., Vucur, Mihael, Luedde, Mark, Paffenholz, Pia, Tacke, Frank, Trautwein, Christian, Ulmer, Tom F., Neumann, Ulf Peter, and Luedde, Tom

Subjects
Adult, Aged, 80 and over, Male, PD-L1, QH301-705.5, Middle Aged, Article, B7-H1 Antigen, Chemistry, Biliary Tract Neoplasms, biliary tract cancer, PD-1, Biomarkers, Tumor, Humans, biomarker, Female, Biology (General), cholangiocarcinoma, QD1-999, Aged
Abstract

International journal of molecular sciences 22(12), 6569 (2021). doi:10.3390/ijms22126569 special issue: "Special Issue "PD-L1, a Master Regulator of Immunity 2.0" / Special Issue Editor: Dr. Grazyna Kochan, Guest Editor", Published by MDPI, Basel

Published
2021
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22. Levels of Circulating PD-L1 Are Decreased in Patients with Resectable Cholangiocarcinoma

Author

Roderburg, Christoph, primary, Loosen, Sven H., additional, Bednarsch, Jan, additional, Alizai, Patrick H., additional, Roeth, Anjali A., additional, Schmitz, Sophia M., additional, Vucur, Mihael, additional, Luedde, Mark, additional, Paffenholz, Pia, additional, Tacke, Frank, additional, Trautwein, Christian, additional, Ulmer, Tom F., additional, Neumann, Ulf Peter, additional, and Luedde, Tom, additional

Published
2021
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24. Circulating levels of microRNA193a-5p predict outcome in early stage hepatocellular carcinoma

Author

Loosen, Sven H., primary, Wirtz, Theresa H., additional, Roy, Sanchari, additional, Vucur, Mihael, additional, Castoldi, Mirco, additional, Schneider, Anne T., additional, Koppe, Christiane, additional, Ulmer, Tom F., additional, Roeth, Anjali A., additional, Bednarsch, Jan, additional, Alizai, Patrick H., additional, Paffenholz, Pia, additional, Demir, Münevver, additional, Trautwein, Christian, additional, Tacke, Frank, additional, Neumann, Ulf P., additional, Roderburg, Christoph, additional, and Luedde, Tom, additional

Published
2020
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26. Circulating levels of microRNA193a-5p predict outcome in early stage hepatocellular carcinoma

Author

Loosen, Sven H., Wirtz, Theresa H., Roy, Sanchari, Vucur, Mihael, Castoldi, Mirco, Schneider, Anne T., Koppe, Christiane, Ulmer, Tom F., Roeth, Anjali A., Bednarsch, Jan, Alizai, Patrick H., Paffenholz, Pia, Demir, Muenevver, Trautwein, Christian, Tacke, Frank, Neumann, Ulf P., Roderburg, Christoph, Luedde, Tom, Loosen, Sven H., Wirtz, Theresa H., Roy, Sanchari, Vucur, Mihael, Castoldi, Mirco, Schneider, Anne T., Koppe, Christiane, Ulmer, Tom F., Roeth, Anjali A., Bednarsch, Jan, Alizai, Patrick H., Paffenholz, Pia, Demir, Muenevver, Trautwein, Christian, Tacke, Frank, Neumann, Ulf P., Roderburg, Christoph, and Luedde, Tom

Abstract

While tumor resection and liver transplantation (LT) represent potentially curative therapeutic options for patients with early-stage hepatocellular carcinoma (HCC), the identification of the ideal surgical candidates has remained challenging. Just recently, miRNA-193a-5p was described as a tumor suppressor in murine and human HCC but only little is known about circulating miRNA-193a-5p in HCC patients. Here, we evaluated serum levels of miR-193a-5p by qPCR in 41 HCC patients undergoing tumor resection (n = 33) or LT (n = 8) and 20 controls. Circulating relative miR-193a-5p levels were significantly elevated in HCC patients compared to healthy controls. While relative miR-193a-5p levels were comparable between patients of different underlying disease etiology and tumor size, high relative miR-193a-5p levels were predictive for the patients' postoperative outcome, which was confirmed in uni- and multivariate Cox-regression analysis. As such, HCC patients with a preoperative relative miR-193a-5p level above the ideal cut-off value (3.57) had a median overall survival (OS) of only 451 days compared to 1158 days in patients with a relative miR-193a-5p level below this cut-off value. Our data support a novel function of miR-193a-5p as a biomarker in early-stage HCC patients that might help to identify the best surgical candidates in terms of postoperative outcome.

Published
2020

27. High baseline soluble urokinase plasminogen activator receptor (suPAR) serum levels indicate adverse outcome after resection of pancreatic adenocarcinoma

Author

Loosen, Sven H, primary, Tacke, Frank, additional, Püthe, Niklas, additional, Binneboesel, Marcel, additional, Wiltberger, Georg, additional, Alizai, Patrick H, additional, Kather, Jakob N, additional, Paffenholz, Pia, additional, Ritz, Thomas, additional, Koch, Alexander, additional, Bergmann, Frank, additional, Trautwein, Christian, additional, Longerich, Thomas, additional, Roderburg, Christoph, additional, Neumann, Ulf P, additional, and Luedde, Tom, additional

Published
2019
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29. High baseline soluble urokinase plasminogen activator receptor (suPAR) serum levels indicate adverse outcome after resection of pancreatic adenocarcinoma

Author

Loosen, Sven H., Tacke, Frank, Puthe, Niklas, Binneboesel, Marcel, Wiltberger, Georg, Alizai, Patrick H., Kather, Jakob N., Paffenholz, Pia, Ritz, Thomas, Koch, Alexander, Bergmann, Frank, Trautwein, Christian, Longerich, Thomas, Roderburg, Christoph, Neumann, Ulf P., Luedde, Tom, Loosen, Sven H., Tacke, Frank, Puthe, Niklas, Binneboesel, Marcel, Wiltberger, Georg, Alizai, Patrick H., Kather, Jakob N., Paffenholz, Pia, Ritz, Thomas, Koch, Alexander, Bergmann, Frank, Trautwein, Christian, Longerich, Thomas, Roderburg, Christoph, Neumann, Ulf P., and Luedde, Tom

Abstract

Surgical resection represents the only potentially curative therapy for patients with pancreatic adenocarcinoma (PDAC), an aggressive malignancy with a very limited 5-year survival rate. However, even after complete tumor resection, many patients are still facing an unfavorable prognosis underlining the need for better preoperative stratification algorithms. Here, we explored the role of the secreted glycoprotein soluble urokinase plasminogen activator receptor (suPAR) as a novel circulating biomarker for patients undergoing resection of PDAC. Serum levels of suPAR were measured by enzyme-linked immunosorbent assay (ELISA) in an exploratory as well as a validation cohort comprising a total of 127 PDAC patients and 75 healthy controls. Correlating with a cytoplasmic immunohistochemical expression of uPAR in PDAC tumor cells, serum levels of suPAR were significantly elevated in PDAC patients compared to healthy controls and patient with PDAC precursor lesions. Importantly, patients with high preoperative suPAR levels above a calculated cutoff value of 5.956 ng/ml showed a significantly reduced overall survival after tumor resection. The prognostic role of suPAR was further corroborated by uni- and multivariate Cox-regression analyses including parameters of systemic inflammation, liver and kidney function as well as clinico-pathological patients' characteristics. Moreover, high baseline suPAR levels identified those patients particularly susceptible to acute kidney injury and surgical complications after surgery. In conclusion, our data suggest that circulating suPAR represents a novel prognostic marker in PDAC patients undergoing tumor resection that might be a useful addition to existing preoperative stratification algorithms for identifying patients that particularly benefit from extended tumor resection.

Published
2019

30. Serum levels of soluble urokinase plasminogen activator receptor (suPAR) predict outcome after resection of colorectal liver metastases

Author

Loosen, Sven H., primary, Tacke, Frank, additional, Binnebosel, Marcel, additional, Leyh, Catherine, additional, Vucur, Mihael, additional, Heitkamp, Florian, additional, Schoening, Wenzel, additional, Ulmer, Tom F., additional, Alizai, Patrick H., additional, Trautwein, Christian, additional, Koch, Alexander, additional, Longerich, Thomas, additional, Roderburg, Christoph, additional, Neumann, Ulf P., additional, and Luedde, Tom, additional

Published
2018
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33. Noninvasive Evaluation of Liver Function in Morbidly Obese Patients.

Author

Alizai, Patrick H., Lurje, Isabella, Kroh, Andreas, Schmitz, Sophia, Luedde, Tom, Andruszkow, Julia, Neumann, Ulf P., and Ulmer, Florian

Subjects
LIVER function tests, OVERWEIGHT persons, FATTY liver, LIVER biopsy, BARIATRIC surgery
Abstract

Background. More than half of the obese patients develop nonalcoholic fatty liver disease (NAFLD), which may further progress to nonalcoholic steatohepatitis (NASH) and cirrhosis. The aim of this study was to assess alterations in liver function in obese patients with a noninvasive liver function test. Methods. In a prospective cohort study 102 morbidly obese patients undergoing bariatric surgery were evaluated for their liver function. Liver function capacity was determined by the LiMAx® test (enzymatic capacity of cytochrome P450 1A2). Liver biopsy specimens were obtained intraoperatively and classified according to the NAFLD Activity Score (NAS). NASH clinical score was additionally calculated from laboratory and clinical parameters. Results. Median liver function capacity was 286 (IQR=141) μg/kg/h. 27% of patients were histologically categorized as definite NASH, 39% as borderline, and 34% as not NASH. A significant correlation was observed between liver function capacity and NAS (r=−0.492; p<0.001). The sensitivity and specificity of the LiMAx® test to distinguish between definite NASH and not NASH were 85.2% and 82.9% (AUROC 0.859), respectively. According to the NASH clinical scoring system, 14% were classified as low risk, 31% as intermediate, 26% as high, and 29% as very high risk. Liver function capacity is also significantly correlated with the NASH clinical scoring system (r=−0.411; p<0.001). Conclusions. Obese patients show a diminished liver function capacity, especially those suffering from type 2 diabetes. The liver function capacity correlates with histological and clinical scoring systems. The LiMAx® test may be a valuable tool for noninvasive screening for NASH in obese patients. [ABSTRACT FROM AUTHOR]

Published
2019
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34. Establishment of a biophysical model to optimize endoscopic targeting of magnetic nanoparticles for cancer treatment

Author

Roeth,Anjali A., Slabu,Ioana, Baumann,Martin, Alizai,Patrick H., Schmeding,Maximilian, Guentherodt,Gernot, Schmitz-Rode,Thomas, Neumann,Ulf P., Roeth,Anjali A., Slabu,Ioana, Baumann,Martin, Alizai,Patrick H., Schmeding,Maximilian, Guentherodt,Gernot, Schmitz-Rode,Thomas, and Neumann,Ulf P.

Abstract

Anjali A Roeth,1,* Ioana Slabu,2,* Martin Baumann,2 Patrick H Alizai,1 Maximilian Schmeding,1 Gernot Guentherodt,3 Thomas Schmitz-Rode,2 Ulf P Neumann1 1Department of General, Visceral and Transplant Surgery, University Hospital RWTH Aachen, 2Institute of Applied Medical Engineering, Helmholtz-Institute Aachen, RWTH Aachen, Aachen, 3Institute of Physics A, RWTH Aachen University, Aachen, Germany *These authors contributed equally to this work Abstract: Superparamagnetic iron oxide nanoparticles (SPION) may be used for local tumor treatment by coupling them to a drug and accumulating them locally with magnetic field traps, that is, a combination of permanent magnets and coils. Thereafter, an alternating magnetic field generates heat which may be used to release the thermosensitively bound drug and for hyperthermia. Until today, only superficial tumors can be treated with this method. Our aim was to transfer this method into an endoscopic setting to also reach the majority of tumors located inside the body. To find the ideal endoscopic magnetic field trap, which accumulates the most SPION, we first developed a biophysical model considering anatomical as well as physical conditions. Entities of choice were esophageal and prostate cancer. The magnetic susceptibilities of different porcine and rat tissues were measured with a superconducting quantum interference device. All tissues showed diamagnetic behavior. The evaluation of clinical data (computed tomography scan, endosonography, surgical reports, pathological evaluation) of patients gave insight into the topographical relationship between the tumor and its surroundings. Both were used to establish the biophysical model of the tumors and their surroundings, closely mirroring the clinical situation, in which we could virtually design, place and evaluate different electromagnetic coil configurations to find optimized magnetic field traps for each tumor entity. By simulation, we could show that the efficiency of the mag

Published
2017

35. Extended Distal Pancreatectomy with En Bloc Resection of the Celiac Axis for Locally Advanced Pancreatic Cancer: A Case Report and Review of the Literature

Author

Alizai, Patrick H., Mahnken, Andreas H., Klink, Christian D., Neumann, Ulf P., and Junge, Karsten

Subjects
Article Subject, digestive system diseases
Abstract

Due to a lack of early symptoms, pancreatic cancers of the body and tail are discovered mostly at advanced stages. These locally advanced cancers often involve the celiac axis or the common hepatic artery and are therefore declared unresectable. The extended distal pancreatectomy with en bloc resection of the celiac artery may offer a chance of complete resection. We present the case of a 48-year-old female with pancreatic body cancer invading the celiac axis. The patient underwent laparoscopy to exclude hepatic and peritoneal metastasis. Subsequently, a selective embolization of the common hepatic artery was performed to enlarge arterial flow to the hepatobiliary system and the stomach via the pancreatoduodenal arcades from the superior mesenteric artery. Fifteen days after embolization, the extended distal pancreatectomy with splenectomy and en bloc resection of the celiac axis was carried out. The postoperative course was uneventful, and complete tumor resection was achieved. This case report and a review of the literature show the feasibility and safety of the extended distal pancreatectomy with en bloc resection of the celiac axis. A preoperative embolization of the celiac axis may avoid ischemia-related complications of the stomach or the liver.

Published
2012
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37. Sarcopenia, obesity and sarcopenic obesity: effects on liver function and volume in patients scheduled for major liver resection

Author

Lodewick, Toine M., primary, Roeth, Anjali A.J., additional, Olde Damink, Steven W.M., additional, Alizai, Patrick H., additional, van Dam, Ronald M., additional, Gassler, Nikolaus, additional, Schneider, Mark, additional, Dello, Simon A.W.G., additional, Schmeding, Maximilian, additional, Dejong, Cornelis H.C., additional, and Neumann, Ulf P., additional

Published
2015
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38. Circulating levels of microRNA193a-5p predict outcome in early stage hepatocellular carcinoma

Author

Loosen, Sven H., Wirtz, Theresa H., Roy, Sanchari, Vucur, Mihael, Castoldi, Mirco, Schneider, Anne T., Koppe, Christiane, Ulmer, Tom F., Roeth, Anjali A., Bednarsch, Jan, Alizai, Patrick H., Paffenholz, Pia, Demir, Münevver, Trautwein, Christian, Tacke, Frank, Neumann, Ulf P., Roderburg, Christoph, and Luedde, Tom

Subjects
Survival Rate, MicroRNAs, ROC Curve, Area Under Curve, Case-Control Studies, Liver Neoplasms, 600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit, 3. Good health, Neoplasm Staging, Proportional Hazards Models, Up-Regulation
Abstract

While tumor resection and liver transplantation (LT) represent potentially curative therapeutic options for patients with early-stage hepatocellular carcinoma (HCC), the identification of the ideal surgical candidates has remained challenging. Just recently, miRNA-193a-5p was described as a tumor suppressor in murine and human HCC but only little is known about circulating miRNA-193a-5p in HCC patients. Here, we evaluated serum levels of miR-193a-5p by qPCR in 41 HCC patients undergoing tumor resection (n = 33) or LT (n = 8) and 20 controls. Circulating relative miR-193a-5p levels were significantly elevated in HCC patients compared to healthy controls. While relative miR-193a-5p levels were comparable between patients of different underlying disease etiology and tumor size, high relative miR-193a-5p levels were predictive for the patients’ postoperative outcome, which was confirmed in uni- and multivariate Cox-regression analysis. As such, HCC patients with a preoperative relative miR-193a-5p level above the ideal cut-off value (3.57) had a median overall survival (OS) of only 451 days compared to 1158 days in patients with a relative miR-193a-5p level below this cut-off value. Our data support a novel function of miR-193a-5p as a biomarker in early-stage HCC patients that might help to identify the best surgical candidates in terms of postoperative outcome.

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