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World Journal of Gastroenterology 2006年第18期12卷 2914-2918页

作者： Helge Kleinhans Oliver Mann Paulus G Schurr jussuf t kaifi Bente Hansen Jakob R Izbicki tim Strate Department of General- Visceral- and Thoracic SurgeryUniversity Medical Center Hamburg-EppendorfMartinistrasse 52D-20246 HamburgGermany

AIM： Microcirculatory dysfunction and free oxygen radicals are important factors in the pathogenesis of severe acute pancreatitis. Additional oxygen delivery might enhance lipid peroxidation but may also improve pancreatic microcirculation. this study assesses the effect of free cellular bovine hemoglobin on the formation of oxygen radicals and microcirculation in a rodent model of severe acute pancreatitis. MEtHODS： Fifteen minutes after induction of acute pancreatitis Wistar rats received either 0.8 mL bovine hemoglobin （HBOC-200）, hydroxyethyl starch （HES） or 2.4 mL of normal saline to ensure normovolemic substitution. After 6 h of examination the pancreas was excised and rapidly processed for indirect measurement of lipid peroxidation products malondialdehyde （MDA） and reduced glutathione （GSH） in pancreatic tissue. RESULtS： the single application of HBOC-200 improved pancreatic microcirculation and reduced histopathological tissue damage significantly. tissue concentration of MDA did not differ between the groups. Also no differences in GSH levels were detected.CONCLUSION： though the single application of HBOC-200 and HES improve pancreatic microcirculation, no differences in lipid peroxidation products were detected. the beneficial effect of additional oxygen supply （HBOC-200） does not lead to enhanced lipid peroxidation.

关键词： Hemoglobin-based-oxygen-carrier HBOC Blood substitudes Severe acute pancreatitis Free oxygen radicals Oxidative stress

L1 is a potential marker for poorly-differentiated pancreatic neuroendocrine carcinoma

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World Journal of Gastroenterology 2006年第1期12卷 94-98页

作者： jussuf t kaifi Ulrich Zinnkann Emre F Yekebas Paulus G Schurr Uta Reichelt Robin Wachowiak Henning C Fiegel Susann Petri Melitta Schachner Jakob RIzbicki Department of General Visceral and Thoracic SurgeryUniversity Medical Center Hamburg-EppendorfHamburgGermany Institute for Pathology University Medical Center Hamburg-EppendorfHamburgGermany Department of Pediatric Surgery University Medical Center Hamburg-EppendorfHamburgGermany Center for Molecular Neurobiology University Medical Center Hamburg-EppendorfHamburgGermany

AIM： to determine the expression of L1 in pancreatic neuroendocrine tumor and to correlate it with WHO classification of this tumor. MEtHODS： We retrospectively analyzed L1 expression in 63 cases of pancreatic neuroendocrine tumor by immunohistochemistry on paraffin sections of primary tumors or metastases. Staining was performed by peroxidase technique with monoclonal antibody U3127.11 against human L1. All tumors were classified according to WHO classification as well-differentiated neuroendo- crine tumors and carcinomas or poorly-differentiated neuroendocrine carcinomas. RESULtS： LI was detected in 5 （7.9%） of 63 pancreatic neuroendocrine tumors. Four （44.4%） of 9 poorlydifferentiated carcinomas expressed L1. In contrast, only 1 （1.9%） of 54 well-differentiated tumors or carcinomas was positive for LI. No expression was found in Langerhans islet cells of normal pancreatic tissue. Cross table analysis showed a significant association between L1 expression and classification of neuroendocrine tumors of the pancreas （P〈0.01）. CONCLUSION： L1 is specifically expressed in poorlydifferentiated pancreatic neuroendocrine carcinomas that are known to have the worst prognosis. L1 might be a marker for risk prediction of patients diagnosed with pancreatic neuroendocrine carcinomas.

关键词： Neuroendocrine pancreatic tumor tumor markers Cell adhesion molecules L1

Association of rare SPINK1 gene mutation with another base substitution in chronic pancreatitis patients

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World Journal of Gastroenterology 2006年第33期12卷 5352-5356页

作者： Viacheslav N Kalinin jussuf t kaifi Heidi Schwarzenbach Anatoly S Sergeyev Bjoern C Link Dean Bogoevski Yogesh Vashist Jakob R Izbicki Emre F Yekebas Department of General Visceral and Thoracic Surgery University Medical Center Hamburg-Eppendorf Hamburg Germany Institute for tumor Biology University Medical Center Hamburg-Eppendorf Hamburg Germany Research Centre for Medical Genetics Moscow Russia

AIM: to verify and expand the known spectrum of serine protease inhibitor Kazal type 1 (SPINK1) gene mutations in chronic pancreatitis. MEtHODS: DNA extracted from 172 chronic pancreatitis patients was assayed for SPINK1 gene mutations by PCR and DNA sequencing. A control cohort of 90 unrelated healthy individuals was analysed by the same methods for presence of common populational polymorphisms, and frequency of five-loci haplotypes was calculated. Linkages of gene aberrations in single SPINK1 gene copies were analysed by long-distance PCR followed by allele-specifi c PCR and DNA sequencing. RESULtS: the most frequent SPINK1 gene mutation N34S was found at a frequency of 6%. Furthermore, we detected the heterozygous intervening sequence (IVS) 3 + 2 t > C mutated gene in 2 German patients and 1 Macedonian chronic pancreatitis patient. In all three SPINK1 gene copies an additional rare base substitution was found: 5’untranslated region (UtR)-215 G > A. Poly-morphism analysis revealed that all three affected genes carried the same fi ve-loci haplotype. DNA sequencing of another chronic pancreatitis-related gene PRSS1 (cationic trypsinogen) did not reveal any mutations in these 3 ***: We found in 3 (2%) of 172 chronic pancreatitis patients an IVS3 + 2 t > C SPINK1 gene mutation and a base substitution 5’UtR-215 G > A inthe same gene copy. Most probably the 5’UtR-215 G >A represents a rare polymorphism and not a mutationas previously concluded. Haplotype analysis suggests acommon origin of the IVS3 + 2 t > C mutation in thesepatients.

关键词： Chronic pancreatitis Serine protease inhibitor Kazal type 1 Gene mutations

Strong prognostic value of nodal and bone marrow micro-involvement in patients with pancreatic ductal carcinoma receiving no adjuvant chemotherapy

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World Journal of Gastroenterology 2006年第40期12卷 6515-6521页

作者： Emre F Yekebas Dean Bogoevski Michael Bubenheim Bjrn-Christian Link jussuf t kaifi Robin Wachowiak Oliver Mann Asad Kutup Guellue Cataldegirmen Lars Wolfram Andreas Erbersdobler Christoph Klein Klaus Pantel Jakob R Izbicki Department of General Visceral and Thoracic Surgery University Medical Centre of Hamburg-Eppendorf Hamburg Germany Institute of Medical Biometry and Epidemiology University Medical Centre of Hamburg-Eppendorf Hamburg Germany Institute of Pathology University Medical Centre of Hamburg-Eppendorf Hamburg Germany Institute of Immunology University of Munich Munich Germany Institute of tumor Biology University Medical Centre of Hamburg-Eppendorf Hamburg Germany

AIM： to study the prognostic value of adjuvant chemotherapy in patients with pancreatic, ductal adenocarcinoma. MEtHODS： Lymph nodes from 106 patients with resectable pancreatic ductal adenocarcinoma were systematically sampled. A total of 318 lymph nodes classified histopathologically as tumor-free were examined using sensitive immunohistochemical assays. Forty-three （41%） of the 106 patients were staged as pt1/2, 63 （59%） as pt3/4, 51 （48%） as pNo, and 55 （52%） as pN1. the study population included 59 （56%） patients exhibiting G1/2, and 47 （44%） patients with G3 tumors. Patients received no adjuvant chemoor radiation therapy and were followed up for a median of 12 （range： 3.5 to 139） mo.RESULtS： Immunostaining with Ber-EP4 revealed nodal microinvolvement in lymph nodes classified as ＂tumor free＂ by conventional histopathology in 73 （69%） out of the 106 patients. twenty-nine （57%） of 51 patients staged histopathologically as pNo had nodal microinvolvement. the five-year survival probability for pN0-patients was 54% for those without nodal microinvolvement and 0% for those with nodal microinvolvement. Cox-regression modeling revealed the independent prognostic effect of nodal microinvolvement on recurrence-free （relative risk 2.92, P = 0.005） and overall （relative risk 2.49, P = 0.009） survival. CONCLUSION： the study reveals strong and independent prognostic significance of nodal microinvolvement in patients with pancreatic ductal adenocarcinoma who have received no adjuvant therapy. the addition of immunohistochemical findings to histopathology reports stratification of patients with may help to improve risk pancreatic cancer.

关键词： Pancreatic ductal adenocarcinoma Nodal microinvolvement Micrometastases

Identifying patient-specific flow of signal transduction perturbed by multiple single-nucleotide alterations

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Quantitative Biology 2020年第4期8卷 336-346页

作者： Olha Kholod Chi-Ren Shyu Jonathan Mitchem jussuf kaifi Dmitriy Shin MU Institute for Data Science and Informatics University of MissouriColumbiaMO 65201USA Department Pathology and Anatomical Sciences School of MedicineUniversity of MissouriColumbiaMO 65212USA Department of Surgery School of MedicineUniversity of MissouriColumbiaMO 65212USA Harry S.truman Memorial Veterans'Hospital ColumbiaMO 65201USA Department of Electrical Engineering&Computer Science University of MissouriColumbiaMO 65212USA

Background:Identifying patient-specific flow of signal transduction perturbed by multiple single-nucleotide alterations is critical for improving patient outcomes in cancer ***,accurate estimation of mutational effects at the pathway level for such patients remains an open *** probabilistic pathway topology methods are gaining interest among the scientific community,the overwhelming majority do not account for network perturbation effects from multiple single-nucleotide ***:Here we present an improvement of the mutational forks formalism to infer the patient-specific flow of signal transduction based on multiple single-nucleotide alterations,including non-synonymous and synonymous *** lung adenocarcinoma and skin cutaneous melanoma datasets from tCGA Pan-Cancer Atlas have been employed to show the utility of the proposed ***:We have comprehensively characterized six mutational *** number of mutated nodes ranged from one to four depending on the topological characteristics of a *** confidences(tCs)have been computed for every possible combination of single-nucleotide alterations in the *** performed analysis demonstrated the capacity of the mutational forks formalism to follow a biologically explainable logic in the identification of high-likelihood signaling routes in lung adenocarcinoma and skin cutaneous melanoma *** findings have been largely supported by the evidence from the biomedical ***:We conclude that the formalism has a great chance to enable an assessment of patient-specific flow by leveraging information from multiple single-nucleotide alterations to adjust the transitional likelihoods that are solely based on the canonical view of a disease.

关键词： mutational forks signaling pathways cancer single-nucleotide alterations

胰腺切除术后出血的诊断与治疗:669例连续胰腺切除术分析

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医学信息（手术学分册） 2008年第4期21卷 317-317页

作者： Yekebas Emre F. Wolfram Lars Cataldegirmen Guellue Habermann Christian R. Bogoevski Dean Koenig Alxandra M. kaifi jussuf Schurr Paulus G. Bubenheim Michael Nolte-Ernsting Claus Adam Gerhard Izbicki Jakob R.

目的:分析胰腺切除术后出血(postpancreatectomy hemorrhage,PPH)的临床病程及预后。背景:PPH是最致命的胰腺术后并发症,但目前仍缺少其标准治疗规程。方法:1992年至2006年,对1524例施行胰腺手术的患者进行了前瞻性研究。根据以下指标进... 详细信息

目的:分析胰腺切除术后出血(postpancreatectomy hemorrhage,PPH)的临床病程及预后。背景:PPH是最致命的胰腺术后并发症,但目前仍缺少其标准治疗规程。方法:1992年至2006年,对1524例施行胰腺手术的患者进行了前瞻性研究。根据以下指标进行PPH危险分级:PPH严重程度(轻度,即血红蛋白浓度下降3g/dL),PPH出现时间(早期,即术后1－5天;晚期,术后第6天),合并胰瘘,肠道内或肠道外出血表现以及存在“复杂的”血管病理变化(腐蚀、假性动脉瘤)。[第一段]

关键词：切除术后出血胰腺切除术标准治疗血红蛋白浓度诊断术后并发症假性动脉瘤 PPH