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Influence of the body mass index on postoperative outcome and long-term survival after pancreatic resections in patients with underlying malignancy

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Hepatobiliary Surgery and Nutrition 2019年第3期8卷 201-210页

作者： Philippa Seika Fritz Klein Uwe Pelzer Johann Pratschke marcus bahra Thomas Malinka Department of Surgery Charite Campus Mitte and Charite Campus Virchow KlinikumCharité-Universitatsmedizin BerlinBerlinGermany Department of Hematology/Oncology/Tumorimmunology Campus Virchow KlinikumCharité-Universitatsmedizin BerlinBerlinGermany

Background:While the long-term survival rate among patients with pancreatic and periampullary carcinomas remains low,it can be influenced by various *** purpose of this retrospective study was to investigate the effects of body mass index(BMI)on postoperative complications and patient survival after pancreatic resections for underlying malignancy over a 20-year observation ***:We analyzed 1,384 patients,918 patients with pancreatic ductal adenocarcinoma(PDAC)(66.3%),229 patients with distal cholangiocarcinoma(16.5%),206 ampullary carcinoma patients(14.8%),and 31 duodenal carcinoma patients(2.2%).Patients were classified into four groups(group 130.0)according to their BMI(kg/m2).We analyzed differences in postoperative complications,postoperative length of hospital stays,reoperations,postoperative mortality and survival rate among the ***:Within a mean observation period of 687.7[2–8,500]days,735(53.1%)patients *** were important differences in postoperative complications(group 1,16.2%;group 2,20.3%;group 3,27.2%,group 4,41.6%)with the type of postoperative complications also varying between the *** 1-,5-,10-and 15-year survival rates were 66.4%,25.5%,17.9%,and 12.1%,respectively,with survival rates varying amongst the four ***:Patients with a BMI between 18.5 and 30 show better postoperative outcomes,regarding complications,hospitalization duration,and reoperation rates than underweight or obese ***-term survival depends strongly on postoperative complications while patients with a higher BMI show better long-term survival rates.

关键词： Pancreatic resection body mass index(BMI) outcome long-term survival

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Matched-pair analysis of postoperative morbidity and mortality for pancreaticogastrostomy and pancreaticojejunostomy using mattress sutures in soft pancreatic tissue remnants

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Hepatobiliary & Pancreatic Diseases International 2012年第1期11卷 89-95页

作者： Fritz Klein marcus bahra Matthias Glanemann Wladimir Faber Peter Warnick Andreas Andreou Safak Gül Dietmar Jacob Department of General Visceraland Transplantation SurgeryCharité-Campus VirchowUniversit tsmedizin Berlin Department of Visceral Vascularand Minimally Invasive SurgeryVivantes Klinikum Spandau

BACKGROUND:After pancreaticoduodenectomy,the incidence of postoperative pancreatic fistula remains high,especially in patients with 'soft' pancreatic tissue *** 'gold standard' surgical technique for pancreaticoenteric anastomosis has been *** study aimed to compare the postoperative morbidity and mortality of pancreaticogastrostomy and pancreaticojejunostomy for 'soft' pancreatic tissue remnants using modified mattress ***:Seventy-five patients who had undergone pancreaticogastrostomy and 75 who had undergone pancreaticojejunostomy after pancreaticoduodenectomy between 2002 and 2008 were retrospectively compared using matched-pair analysis.A modified mattress suture technique was used for the pancreaticoenteric *** with an underlying 'hard' pancreatic tissue remnant,as in chronic pancreatitis,were *** groups were homogeneous for age,gender,and underlying *** morbidity,mortality,and preoperative and operative data were ***:There were no significant differences between the groups for the incidence of postoperative pancreatic fistula (10.7% in both).Postoperative morbidity and mortality,median operation time,median length of hospital stay,intraoperative blood loss,and the amount of intraoperatively transfused erythrocyte concentrates also did not significantly differ between the *** age >65 years (P=0.017),operation time >350minutes (P=0.001),and intraoperative transfusion of erythrocyte concentrates (P=0.038) were identified as risk factors for postoperative ***:Our results showed no significant differences between the groups in the pancreaticogastrostomy and pancreaticojejunostomy anastomosis techniques using mattress sutures for 'soft' pancreatic tissue *** our experience,the mattress sutures are safe and simple to use,and pancreaticogastrostomy in particular is feasible and easy to learn,with good endoscopic accessibility to the anastomos

关键词： mattress sutures pancreaticoduodenectomy pancreaticogastrostomy pancreaticojejunostomy soft pancreatic tissue remnant

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Sirolimus inhibits growth of human hepatoma cells alone or combined with tacrolimus, while tacrolimus promotes cell growth

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World Journal of Gastroenterology 2005年第10期11卷 1420-1425页

作者： Guido Schumacher Marijke Oidtmann Anne Rueggeberg Dietmar Jacob Sven Jonas Jan M. Langrehr Ruth Neuhaus marcus bahra Peter Neuhaus Departments of General Department of Anesthesiology

AIM: Standard immunosuppression after organ transplantation stimulates tumor growth. Sirolimus has a strong antiproliferative and a tumor inhibiting effect. The purpose is to assess the effect on tumor growth of the immunosuppressive compounds sirolimus and tacrolimus alone and in combination on cells of human hepatocellular ***: We used the human cell lines SK-Hep 1 and Hep 3B derived from hepatocellular carcinoma. Proliferation analyses after treatment with sirolimus, tacrolimus, or the combination of both were performed. FACS analyses were done to reveal cell cycle changes and apoptotic cell death. The expression of apoptosis-related proteins was estimated by Western ***: Sirolimus alone or combined with tacrolimus inhibited the growth of both cell lines after 5 d by up to 35% in SK-Hep 1 cells, and by up to 68% in Hep 3B cells at 25 ng/mL. Tacrolimus alone stimulated the growth by 12% after 5 ng/mL and by 25% after 25 ng/mL in Hep 3B cells. We found an increase of apoptotic Hep 3B cells from 6 to 16%, and a G1-arrest in SK-Hep 1 cells with an increase of cells from 61 to 82%, when sirolimus and tacrolimus were combined. Bcl-2 was down-regulated in Hep 3B, but not in SK-Hep 1 cells after combined ***: Sirolimus appears to inhibit the growth of hepatocellular carcinoma cells alone and in combination with tacrolimus. Sirolimus seems to inhibit the growth stimulation of tacrolimus.

关键词： Sirolimus Tacrolimus Hepatocellular carcinoma Growth inhibition Apoptosis SK-Hep 1 Hep3B

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Tumor–stromal cross-talk modulating the therapeutic response in pancreatic cancer

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Hepatobiliary & Pancreatic Diseases International 2018年第5期17卷 461-472页

作者： Christopher C.M.Neumann Ellen von Horschelmann Anja Reutzel-Selke Elisabeth Seidel Igor Maximilian Sauer Johann Pratschke marcus bahra Rosa Bianca Schmuck Department of Surgery Campus Charité Mitte Campus Virchow-KlinikumExperimental SurgeryCharité-Universitatsmedizin BerlinBerlinGermany Berlin Institute of Health Department of SurgeryCampus CharitéMitte and Campus Virchow-KlinikumAugustenburger Platz 113353 BerlinGermany

Background: Pancreatic ductal adenocarcinoma(PDAC) is a highly malignant solid tumor with a dismal prognosis. The stroma component makes up to 90% of the tumor mass and is thought to be one of the main reasons for the tumor’s high chemoresistance. Cancer associated fibroblasts(CAFs) have previously been identified to be the key stromal players. This is the first time we provide detailed in vitro experiments investigating tumor–stromal interactions when exposed to three well-known chemotherapeutic agents. Methods: Monocultures, indirect and direct co-cultures of two PDAC cell lines(AsPC and Panc-1) and six primary patients derived CAFs were treated with gemcitabine, nab-paclitaxel and the γ-secretaseinhibitor(GSI) DAPT. The cell viability of each component was measured with XTT. Finally, IL-6 concentrations of the supernatants were analyzed. Results: On the contrary to PDAC cell lines, CAF monocultures hardly responded to any treatment which suggested that stroma(CAFs) itself is more resistant to standard chemo-treatments than the epithelial cancer cells. Moreover, only a weak chemotherapeutic response was observed in direct co-cultures of cancer cells with CAFs. A change in the morphology of direct co-cultures was accompanied with the chemoresistance. CAFs were observed to build cage-like structures around agglomerates of tumor cells. High levels of IL-6 were also associated with a reduced response to therapy. Indirect co-cultures make the tumor–stromal interaction more complex. Conclusions: CAFs are highly chemoresistant. Direct cell–cell contact and high levels of IL-6 correlate with a high chemoresistance.

关键词： Pancreatic cancer Tumor microenvironment Cancer associated fibroblasts Cancer–stroma co-culture Atroma targeted therapy

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An inflammatory subtype of pancreatic ductal adenocarcinoma is associated with poor prognosis and increased perioperative mortality

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Journal of Pancreatology 2019年第3期2卷 107-112页

作者： Benzing Christian Klein Fritz Pelzer Uwe Sinn Marianne Pratschke Johann bahra marcus Campus Charité-Mitte and Campus Virchow Klinikum Charité-Universitätsmedizin BerlinBerlinGermany Department of Hematology Oncology and Tumor ImmunologyCharité-Universitätsmedizin BerlinBerlinGermany

Pancreatic ductal adenocarcinoma(PDAC)is a malignancy characterized by an aggressive tumor *** present analysis seeks to identify and analyze a cohort that meets criteria for"inflammatory"PDAC(IPDAC).All patients who underwent a curative resection for PDAC at our institution between 1989 and 2015 were included in the retrospective *** with histological proven adenocarcinoma and elevated C-reactive protein(CRP)(≥6 mg/L)serum concentrations,but no other suspicion of infection were *** provide a matched control group with normal CRP serum levels from the same patient ***-six(6.8%)of 532 patients meet our criteria for an IPDAC group ***-hospital(30 days)mortality was 13.9%in the IPDAC group vs 0%in the control group(P=.020).Median follow-up was 183.8 months(standard deviation[SD]=53.3,range 14.3-285.4).Median overall survival was 8.5 months(SD=16.8,range 0.3-89.6)in the IPDAC group and 24.8 months(SD=19.4,range 0.7-80.4)in the control group(P=.002).Patients indicating an IPDAC in our cohort had a significantly and clinical meaningful decreased overall survival and a higher perioperative morbidity and mortality.

关键词： Cholangitis CRP Inflammatory carcinoma PDAC

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Perioperative treatment options in resectable pancreatic cancer-how to improve long-term survival

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World Journal of Gastrointestinal Oncology 2016年第3期8卷 248-257页

作者： Marianne Sinn marcus bahra Timm Denecke Sue Travis Uwe Pelzer Hanno Riess Department of Medical Oncology and Haematology Charité-Universitatsmedizin Berlin Department of General Visceral and Transplantation SurgeryCharité-Universitatsmedizin Berlin Institute of Radiology Charité-Universitatsmedizin Berlin

Surgery remains the only chance of cure for pancreatic cancer, but only 15%-25% of patients present with resectable disease at the time of primary diagnosis. Important goals in clinical research must therefore be to allow early detection with suitable diagnostic procedures, to further broaden operation techniques and to determine the most effective perioperative treatment of either chemotherapy and/or radiation therapy. More extensive operations involving extended pancreatectomy, portal vein resection and pancreatic resection in resectable pancreatic cancer with limited liver metastasis, performed in specialized centers seem to be the surgical procedures with a possible impact on survival. After many years of stagnation in pharmacological clinical research on advanced pancreatic ductal adenocarcinomas(PDAC)- since the approval of gemcitabine in 1997- more effective cytotoxic substances(nab-paclitaxel) and combinations(FOLFIRINOX) are now available for perioperative treatment. Additionally, therapies with a broader mechanism of action are emerging(stroma depletion, immunotherapy, antiinflammation), raising hopes for more effective adjuvant and neoadjuvant treatment concepts, especially in the context of "borderline resectability". Only multidisciplinary approaches including radiology, surgery, medical and radiation oncology as the backbones of the treatment of potentially resectable PDAC may be able to further improve the rate of cure in the future.

关键词： Pancreatic cancer Perioperative treatment Perioperative radiology Chemotherapy

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Evaluating twenty-years of follow-up after orthotopic liver transplantation, best practice for donor-recipient matching: What can we learn from the past era?

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World Journal of Transplantation 2016年第3期6卷 599-607页

作者： Niklas Buescher Daniel Seehofer Michael Helbig Andreas Andreou marcus bahra Andreas Pascher Johann Pratschke Wenzel Schoening Department of General Visceral and Transplantation Surgery Charité Campus Virchow Klinikum Department of General Visceral and Transplantation Surgery University Hospital

AIM To characterize major determinants of 20-year survival after liver transplantation(LT).METHODS This longitudinal single-institution study includes 313 consecutive patients who received a LT between 1988 and 1992. Pretransplant clinical characteristics and laboratory values were assessed and compared between 20-year survivors and non-survivors. Particular attention was paid to the Model for End-Stage Liver Disease(labM ELD)-score and the Eurotransplant Donor Risk Index(ET-DRI) to unravel their impact on 20-year survival after *** Twenty-year survivors were significantly younger(44 vs 50 years, P = 0.001), more likely to be female(49% vs 36%, P = 0.03) and less likely to be obese at the time of LT(19% vs 32%, P = 0.011). Mean labM ELD-score(P = 0.156), rate of high-urgency LT(P = 0.210), coldischemia time(P = 0.994), rate of retransplantation(P = 0.12) and average donor age(28 vs 33 years, P = 0.099) were not statistically different. The mean estimated glomerular filtration rate was higher among survivors(P = 0.007). ET-DRI > 1.4(P = 0.020) and donor age ≥ 30 years(P < 0.022) had significant influence on 20-year survival. The overall survival was not significantly impacted by labM ELD-score categories(P = 0.263).CONCLUSION LT offers excellent long-term results in case of optimal donor and recipient conditions. However, mainly due to the current organ shortage, these ideal circumstances are rarely given; thus algorithms for donor-recipient matching need to be refined, in order to enable a maximum benefit for the recipients of high quality as well as marginal organs.

关键词： Liver transplantation Long-term outcome Ideal recipient Recipient characteristics Donor-recipient matching

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Characterization of the Stem Cell Fraction in Pancreatobiliary Carcinomas: The Notch Signaling Pathway as a Potential Therapeutic Target

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Journal of Cancer Therapy 2018年第6期9卷 480-502页

作者： Elisabeth Seidel Cynthia de Carvalho Fischer Christopher Neumann Anja Reutzel-Selke Andreas Andreou Joseph Gassner Julia Gogolok Peter Tang Anja Schirmeier Fritz Klein Igor M. Sauer Johann Pratschke marcus bahra Rosa B. Schmuck Charité—Universitatsmedizin Berlin Corporate Member of Freie Universitat Berlin Humboldt-Universitatzu Berlin and Berlin Institute of Health Institute of Surgery Augustenburger Platz 1 Berlin Germany

Pancreatic adenocarcinoma (PDAC) and extrahepatic cholangiocarcinoma (ECC) are highly lethal malignancies with limited treatment options. Both a small subpopulation of cancer stem cells (CSC) and the deregulation of the notch pathway have been considered potential sources of tumor formation. In this study, flow cytometry (FCM) was conducted to identify the CSC population and Notch-associated proteins in ECC and PDAC cell lines. Additionally, the treatment effect of Gemcitabine and the specific notch-inhibitor DAPT on ECC and PDAC cell lines was evaluated. Our results show that the amount of SP cells in ECC cell lines is significantly higher than in PDAC cell lines, and that SP-ECC cells show a higher sensitivity to therapy. In conclusion, inhibition of Notch signaling with DAPT may be of therapeutic value in ECC, but seems to show no effect on more aggressive PDAC. As it could be essential for the improvement in outcomes of the ECC patients, other trials are needed to determine the role of further Notch components.

关键词： Notch Pathway Cancer Stem Cells Pancreatic Adenocarcinoma Extrahepatic Cholangiocarcinoma Targeted Therapy

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