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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

Acute scrotum due to arterial bleeding mimicking non-seminomatous germ cell tumor

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Asian Journal of Andrology 2004年第4期6卷 379-381页

作者： F.Christoph M.Schrader A.Amirmaki K.Miller department of Urology Department of UrologyDepartment of PathologyDepartment of Urology Charité Charité Charité Universitatsmedizin Berlin Campus Benjamin Franklin Berlin Germany Charité

Men with testicular tumors usually present with painless increase in testis size incidentally noticed by the patient. We report a case of a young patient presenting as an emergency with acute onset of massive right-sided testicular pain without previous injury. After physical examination testicular torsion could not be excluded. Ultrasound examination of the testis was suspicious for testicular tumor. Surgical exploration of the right testis by inguinal approach was performed revealing subcapsular arterial bleeding due to a small nonseminomatous germ cell tumor non-palpable on clinical examination.

关键词： acute scrotum hemorrhage testicular cancer

Extended surgical resection for xanthogranulomatous cholecystitis mimicking advanced gallbladder carcinoma: A case report and review of literature

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World Journal of Gastroenterology 2006年第14期12卷 2293-2296页

作者： Antonino Spinelli Guido Schumacher Andreas Pascher Enrique Lopez-Hanninen Hussain Al-Abadi Christoph Benckert Igor M Sauer Johann Pratschke Ulf P Neumann Sven Jonas Jan M Langrehr Peter Neuhaus department of General Visceral and Transplantation Surgery Charitè-Universitatsmedizin BerlinCampus Virchow KlinikumAugustenburger Platz 113353 BerlinGermany department of radiology charitè-universitatsmedizin berlin Campus Virchow KlinikumAugustenburger Platz 113353 BerlinGermany

Xanthogranulomatous cholecystitis （XGC） is a destructive inflammatory disease of the gallbladder, rarely involving adjacent organs and mimicking an advanced gallbladder carcinoma. The diagnosis is usually possible only after pathological examination. A 46 year-old woman was referred to our center for suspected gallbladder cancer involving the liver hilum, right liver lobe, right colonic flexure, and duodenum. Brushing cytology obtained by endoscopic retrograde cholangiography （ERC） showed high-grade dysplasia. The patient underwent an en-bloc resection of the mass, consisting of right Iobectomy, right hemicolectomy, and a partial duodenal resection. Pathological examination unexpectedly revealed an XGC. Only six cases of extended surgical resections for XGC with direct involvement of adjacent organs have been reported so far. In these cases, given the possible coexistence of XGC with carcinoma, malignancy cannot be excluded, even after cytology and intraoperative frozen section investigation. In conclusion, due to the poor prognosis of gallbladder carcinoma on one side and possible complications deriving from highly aggressive inflammatory invasion of surrounding organs on the other side, it seems these cases should be treated as malignant tumors until proven otherwise. Clinicians should include XGC among the possible differential diagnoses of masses in liver hilum.

关键词： Xanthogranulomatous cholecystitis Gallbladder cancer Gallbladder carcinoma

Phlegmonous appendicitis in children is characterized by eosinophilia in white blood cell counts

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World Journal of Pediatrics 2018年第5期14卷 504-509页

作者： Maximiliane I.Minderjahn Dag Schadlich Josephine Radtke Karin Rothe Marc Reismann department of Pediatric Surgery Charité–Universitatsmedizin BerlinAugustenburger Platz 113353 BerlinGermany

Background Phlegmonous and complicated appendicitis represent independent entities depending on hereditary immuno-logical mechanisms. However, clinically there are no means to distinguish uncomplicated phlegmonous from complicated appendicitis. The ability to distinguish these two forms of appendicitis is relevant as current attempts are to treat both forms of the disease differently. The aim of the present study was to investigate differences in white blood cell counts (WBCs) in these conditions to identify areas of interest for future molecular studies. Methods White blood cell counts of patients aged between 7 and 14 years who underwent appendectomy from January 2008 to June 2016 were investigated with special reference to particular cellular subpopulations. Results A total of 647 children were included in the study. Within distinct inflammatory patterns, significant eosinophilia and basophilia were found in phlegmonous inflammation compared with complicated inflammation (0.11±0.19×109/L vs. 0.046±0.104×109/L, P<0.0001, and 0.033±0.031×109/L vs. 0.028±0.024×109/L, P<0.001). Conclusions Compared with complicated disease, phlegmonous appendicitis seems to depend primarily on eosinophil inflam-mation. This observation is stable over time and indicates a direction for investigation of underlying genetic prerequisites.

关键词： Appendicitis Children Eosinophil granulocytes Immunology

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

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

Impact of humic acids on the colonic microbiome in healthy volunteers

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World Journal of Gastroenterology 2017年第5期23卷 885-890页

作者： Alexander Swidsinski Yvonne Dorffel Vera Loening-Baucke Christoph Gille Anne Reiβhauer Onder Goktas Monika Krüger Jürgen Neuhaus Wieland Schrodl Laboratory for Molecular Genetics Polymicrobial Infections and BiofilmsDepartment of MedicineSection of GastroenterologyHepatology and EndocrinologyCharitéUniversitatsmedizin Berlin Outpatient Clinic Luisenstr.11-13CharitéUniversitatsmedizin Berlin entre for Infectious Diseases Faculty of Veterinary MedicineUniversity of Leipzig

AIMTo test the effects of humic acids on innate microbial communities of the *** followed the effects of oral supplementation with humic acids (Activomin®) on concentrations and composition of colonic microbiome in 14 healthy volunteers for 45 d. 3 × 800 mg Activomin® were taken orally for 10 d followed by 3 × 400 mg for 35 d. Colonic microbiota were investigated using multicolor fluorescence in situ hybridization (FISH) of Carnoy fixated and paraffin embedded stool cylinders. Two stool samples were collected a week prior to therapy and one stool sample on days 10, 31 and 45. Forty-one FISH probes representing different bacterial groups were *** sum concentration of colonic microbiota increased from 20% at day 10 to 30% by day 31 and remained stable until day 45 (32%) of humic acid supplementation (P 0.05). The others remained unaffected. Bacterial groups with initially marginal concentrations (9/mL) demonstrated no response to humic acids. The concentrations of pioneer groups of Bifidobacteriaceae, Enterobacteriaceae and Clostridium difficile increased but the observed differences were statistically not *** acids have a profound effect on healthy colonic microbiome and may be potentially interesting substances for the development of drugs that control the innate colonic microbiome.

关键词： Fluorescence in situ hybridization Colonic microbiota Colonic bioreactor Humic acids Healthy volunteers Oral supplementation

CT-guided high-dose-rate brachytherapy in the interdisciplinary treatment of patients with liver metastases of pancreatic cancer

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Hepatobiliary & Pancreatic Diseases International 2015年第5期14卷 530-538页

作者： Gero Wieners Alexander Christian Schippers Federico Collettini Dirk Schnapauff Bernd Hamm Peter Wust Hanno Riess Bernhard Gebauer department of Diagnostic and Interventional radiology Charité-Universit?tsmedizin Berlin Campus Virchow-Klinikum department of Radiation Oncology Charité-Universit?tsmedizin Berlin Campus Virchow-Klinikum department of Oncology Charité-Universit?tsmedizin Berlin Campus Virchow-Klinikum

BACKGROUND： CT-guided high-dose-rate brachytherapy（CT-HDRBT） is an interventional radiologic technique for local ablation of primary and secondary malignomas applying a radiation source through a brachycatheter percutaneously into the targeted lesion. The aim of this study was to assess local tumor control, safety and efficacy of CT-HDRBT in the treatment of liver metastases of pancreatic cancer. METHODS： Twenty consecutive patients with 49 unresectable liver metastases of pancreatic cancer were included in this retrospective trial and treated with CT-HDRBT, applied as a single fraction high-dose irradiation（15-20 Gy） using a 192 Irsource. Primary endpoint was local tumor control and secondary endpoints were complications, progression-free survival and overall ***： The mean tumor diameter was 29 mm（range 10-73）. The mean irradiation time was 20 minutes（range 7-42）. The mean coverage of the clinical target volume was 98%（range 88%-100%）. The mean D100 was 18.1 Gy and the median D100 was 19.78 Gy. Three major complications occurred with post-interventional abscesses, three of which were seen in 15 patients with biliodigestive anastomosis（20%）and overall 15%. The mean follow-up time was 13.7 months（range 1.4-55.0）. The median progression-free survival was 4.9 months（range 1.4-42.9, mean 9.4）. Local recurrence occurred in 5（10%） of 49 metastases treated. The median overall survival after CT-HDRBT was 8.6 months（range 1.5-55.3）. Eleven patients received chemotherapy after ablation with a median progression-free survival of 4.9 months（mean 12.9）. Nine patients did not receive chemotherapy after intervention with a median progression-free survival of 3.2 months（mean 5.0）. The rate of local tumor control was 91% in both groups after 12 ***： CT-HDRBT was safe and effective for the treatment of liver metastases of pancreatic cancer.

关键词： brachytherapy pancreatic cancer liver metastases CT intervention

Substrate topography as a powerful tool to modify glial cell biology and interactions

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Neural Regeneration Research 2025年第5期20卷 1390-1391页

作者： Pascal Achenbach Haktan Altinova Gary A.Brook Institute of Neuropathology RWTH Aachen University Hospital department of Neurosurgery RWTH Aachen University Hospital Aachen Germany berlin State Office for Health and Social Affairs(LAGeSo) BerlinGermany

Traumatic injuries to the central nervous system(CNS) result in disruption of the intricate network of axons which connect functionally related neurons that are widely distributed throughout the brain and spinal *** normal conditions,maintenance of this complex system is structurally and functionally supported by astrocytes (ACs)and other glial cells,the processes of which form a framework surrounding neuronal cell bodies,dendrites,axons,and synapses.

关键词： injuries topography system