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Regional lymphadenectomy strongly recommended in T1b gallbladder cancer

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World Journal of Gastroenterology 2011年第38期17卷 4347-4348页

作者： Ulrich Klaus Fetzner arnulf h hlscher Dirk L Stippel Department of General Visceral and Cancer SurgeryUniversity Hospital of Cologne

This article discusses the adequate treatment of early gallbladder cancer （Tla, Tlb） and is based on published studies extending over nearly 3 decades. Ran- domized studies and meta analyses comparing different surgical treatments do not exist. The literature shows that in up to 20% of patients lymph node metastasis are found in Tlb gallbladder cancer. Due to high malignancy with early angiolymphatic spread and resistance to chemotherapy and radiation on the one hand, and the relative low operative risk of extended cholecystectomy （cholecystectomy and regional lymphadenectomy） on the other hand, we believe that this procedure is mandatory in early gallbladder cancer.

关键词： Gallbladder cancer Long-term survival Lymphadenectomy Surgical treatment

Neoadjuvant treatment for advanced esophageal cancer: response assessment before surgery and how to predict response to chemoradiation before starting treatment

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Chinese Journal of Cancer Research 2015年第3期27卷 221-230页

作者： Elfriede Bollschweiler arnulf h.hlscher Matthias Schmidt Ute Warnecke-Eberz Department of General Visceral and Cancer SurgeryUniversity of Cologne Institute of Nuclear Medicine University of Cologne

Patients with advanced esophageal cancer（T3-4, N） have a poor prognosis. Chemoradiation or chemotherapy before esophagectomy with adequate lymphadenectomy is the standard treatment for patients with resectable advanced esophageal carcinoma. however, only patients with major histopathologic response（regression to less than 10% of the primary tumor） after preoperative treatment will have a prognostic benefit of preoperative chemoradiation. Using current therapy regimens about 40% to 50% of the patients show major histopathological response. The remaining cohort does not benefit from this neoadjuvant approach but might benefit from earlier surgical resection. Therefore, it is an aim to develop tools for response prediction before starting the treatment and for early response assessment identifying responders. The current review discusses the different imaging techniques and the most recent studies about molecular markers for early response prediction. The results show that [^18F]-fluorodeoxyglucose-positron emission tomography（FDGPET） has a good sensitivity but the specificity is not robust enough for routine clinical use. Newer positron emission tomography detector technology, the combination of FDG-PET with computed tomography, additional evaluation criteria and standardization of evaluation may improve the predictive value. There exist a great number of retrospective studies using molecular markers for prediction of response. Until now the clinical use is missing. But the results of first prospective studies are promising. A future perspective may be the combination of imaging technics and special molecular markers for individualized therapy. Another aspect is the response assessment after finishing neoadjuvant treatment protocol. The different clinical methods are discussed. The results show that until now no non-invasive method is valid enough to assess complete histopathological response.

关键词： Esophageal cancer squamous cell carcinoma adenocarcinoma neoadjuvant chemoradiation response prediction response assessment

Neoadjuvant chemoradiotherapy for esophageal cancer:Impact on extracapsular lymph node involvement

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World Journal of Gastroenterology 2010年第16期16卷 1986-1992页

作者： Ralf Metzger Elfriede Bollschweiler Uta Drebber Stefan P Mnig Wolfgang Schrder hakan Alakus Martin Kocher Stephan E Baldus arnulf h hlscher Department of General Visceral and Cancer SurgeryCenter for Integrated OncologyUniversity Hospital of Cologne Department of Pathology University of Cologne Department of Radiation Oncology University of Cologne Department of Pathology University of Düsseldorf

AIM:To assess the effects of neoadjuvant chemoradiotherapy(CRT) on the presence of extracapsular lymph node involvement(LNI) and its prognostic value in patients with resected esophageal ***:Two hundred and ninety-eight patients with advanced esophageal cancer underwent esophagectomy between 1997 and *** hundred and ninety patients(63.8%) were treated with neoadjuvant CRT prior to resection.A total of 986 metastatic LNs were *** of the patients was analyzed according to intra-and extra-capsular ***:Five-year survival rate was 22.5% for the entire patient *** with extracapsular LNI had a 5-year survival rate of 16.7%,which was comparable to the 15.8% in patients with infiltrated nodes of the celiac trunk(pM1lymph).In contrast to patients treated with surgery alone,neoadjuvant therapy resulted in signif icantly(P = 0.001) more patients with pN0/M0(51.6% vs 25.0%).In 17.6% of the patients with surgery alone vs 16.8% with neoadjuvant CRT,extracapsular LNI was *** therapy does not reduce the occurrence of extracapsular ***:Extracapsular LNI is an independent negative prognostic factor not influenced by neoadjuvant *** a revised staging system for esophageal cancer,extracapsular LNI should be considered.

关键词： Esophageal cancer Neoadjuvant therapy Chemotherapy Radiotherapy Adenocarcinoma Squamous cell carcinoma Lymph node metastasis Extracapsular lymph node involvement Prognosis

Co-expression of CDX2 and MUC2 in gastric carcinomas: Correlations with clinico-pathological parameters and prognosis

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World Journal of Gastroenterology 2005年第21期11卷 3182-3188页

作者： Kristina Roessler Stefan P.M(o|¨)nig Paul M.Schneider Franz-Georg hanisch Stephanie Landsberg Juergen Thiele arnulf h.h(o|¨)lscher hans P.Dienes Stephan E.Baldus Institute of Pathology University of Cologne 50931 Cologne Germany Department of Visceral and Vascular Surgery University of Cologne 50931 Cologne Germany Center of Biochemistry University of Cologne Cologne Germany Institute of Pathology University of Cologne 50931 CologneGermany Department of Visceral and Vascular Surgery University of Cologne 50931 Cologne Germany

AIM: To evaluate the role of CDX2 homeobox protein as a predictor for cancer progression and prognosis as well as its correlation with MUC2 expression. CDX2 represents a transcription factor for various intestinal genes (including MUC2) and thus an important regulator of intestinal differentiation, which could previously be identified in gastric carcinomas and intestinal metaplasia. METhODS: Formalin-fixed and paraffin-embedded tissues from 190 gastric carcinoma patients were stained with monodonal antibodies recognizing CDX2 and MUC2, respectively. Immunoreactivity was evaluated semiquantitatively and statistical analyses including x2 tests, uni- and multi-variate survival analyses were performed. RESULTS: CDX2 was mostly expressed in a nuclear or supranuclear pattern,whereas MUC2 showed an almost exclusive supranuclear *** antigens were present in >80% of areas exhibiting intestinal metaplasia. An immunoreactivity in >5% of the tumor area was observed in 57% (CDX2) or in 21% (MUC2) of the *** presence of both molecules did not correlate with WhO, Lauren and Goseki classification (with the exception of a significantly stronger MUC2 expression in mucinous tumors). CDX2 correlated with a lower pT and pN stage in the subgroups of intestinal and stage I cancers and was associated with MUC2 positivity.A prognostic impact of CDX2 or MUC2 was not observed. CONCLUSION: CDX2 and MUC2 play an important role in the differentiation of normal, inflamed, and neoplastic gastric tissues. According to our results, loss of CDX2 may represent a marker of tumor progression in early gastric cancer and carcinomas with an intestinal phenotype.

关键词： CDX2 MUC2 Monoclonal antibody Gastric carcinoma Prognosis

Association of the GNAS1 T393C polymorphism with tumor stage and survival in gastric cancer

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World Journal of Gastroenterology 2009年第48期15卷 6061-6067页

作者： hakan Alakus Stefan P Mnig Ute Warnecke-Eberz Gül Alakus Günther Winde Uta Drebber Klaus J Schmitz Kurt W Schmid Kathrin Riemann Winfried Siffert Elfriede Bollschweiler arnulf h hlscher Ralf Metzger Department of General Visceral and Cancer SurgeryCenter for Integrated OncologyUniversity of Cologne Department of Gastrointestinal Surgery Klinikum Herford Institute of Pathology University of Cologne Institute of Pathology and Neuropathology University Hospital of EssenUniversity of Duisburg-Essen Institute of Pharmaco-genetics University Hospital of EssenUniversity of Duisburg-Essen

AIM： To analyze the impact of the GNAS1 T393C polymorphism on prognosis and histopathology of gastric cancer. METhODS： Genomic DNA was extracted from paraffinembedded tissues of 122 patients with primary gastric carcinoma and from the blood of 820 healthy white individuals. Allelic discrimination was performed by quantitative real-time polymerase chain reaction. Genotyping was correlated with histopathologic parameters and with overall survival according to the Kaplan-Meier approach and with multivariate analysis by multiple stepwise regression. RESULTS： Thirty-nine （32%） patients displayed a CC genotype, 57 （46.7%） a CT genotype and 26 （21.3%） a TT genotype. The frequency of the C allele （fC） in the patient group was 0.55, which was not significantly different from that of healthy blood donors. The distribution was compatible with the hardy-Weinberg equilibrium. Analysis of clinicopathological parameters did not show any significant correlation of the T393C genotype with gender （P = 0.50）, differentiation （P = 0.29）, pT-category （P = 0.19）, pN-category （P = 0.30）, pM-category （P = 0.25）, R-category （P = 0.95）, the classifications according to WhO （P = 0.34）, Lauren （P = 0.16）, Goseki （P = 1.00） and Ming （P =0.74）. Dichotomization between C＋（CC＋CT） and C-genotypes （FI）, however, revealed significantly more advanced tumor stages （P = 0.023） and lower survival rates （P = 0.043） for C allele carriers. CONCLUSION： The present study provides strong evidence to suggest that the GNAS1 T393C allele carrier status influences tumor progression and survival in gastric cancer with higher tumor stages and a worse outcome for C allele carriers.

关键词： Gastric cancer G Protein Polymorphism Prognosis Tumor stage

Monitoring of Tumor Response to Neoadjuvant Radio-Chemotherapy of Esophageal Carcinoma by F-18-FDG-PET

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Oncology and Translational Medicine 2004年第4期 64-69页

作者： Peter Theissen,Paul M. Schneider,Stephan E. Baldus,Alexandra Jost,Markus Dietlein,Rolf P. Mller,arnulf h. hlscher,harald Schicha Department of Nuclear Medicine University of Cologne Department of Visceral- and Vascular Surgery University of Cologne Department of Pathology University of Cologne Department of Nuclear Medicine University of Cologne Department of Nuclear Medicine University of Cologne Department of Radiation Therapy University of Cologne Department of Visceral- and Vascular Surgery University of Cologne Department of Nuclear Medicine University of Cologne Cologne Germany Cologne Germany Cologne Germany Cologne GermanyDepartment of Visceral- and Vascular Surgery University of CologneCologne Germany Cologne Germany Cologne Germany Cologne Germany Cologne Germany

Introduction: For clinical assessment of neoadjuvant radiochemotherapy of esophageal cancer reliable in-vivo methods are necessary. Therefore, the capabilities of F-18-Fluorodesoxyglucose-PET in comparison to histomorphological grading of tumor regression were studied. Methods: In 33 patients with locally advanced esophageal carcinoma (uT3, uN0-1, cM0) F-18-FDG-PET was performed before and 2 weeks after radiochemotherapy. All tumors were resected by transthoracic en-bloc esophagectomy 3–4 weeks after induction therapy. A subgroup of 11 patients underwent weekly PET scan during neoadjuvant therapy. PET was performed in a dedicated scanner 1.3 h after administration of 370 MBq F-18-FDG. Data analysis based on maximum SUV data derived from individual regions of interest in pre- and posttherapeutic images. PET data were compared to histomorphological grading parameters for tumor regression whithin the resected tissues. Results: The comparison of histopathological tumor regression after neoadjuvant therapy and PET SUV di?erences showed a signi?cant χ2 P -value of 0.006. There was a signi?cant decrease 五笔字型计算机汉字输入技术 of the SUV data from 9.1±3.5 to 4.3±1.9 (P herapy responders SUV was diminished by 59 % and in non-responders by 34 %. Longitudinal SUV measurement during neoadjuvant therapy showed a strong SUV decrease already after one and two weeks (P =0.021 and 0.003). Conclusion: The recent data of the FDG-PET follow-up after neoadjuvant therapy show that PET is able to predict therapy response. Longitudinal PET data advocate that it may be possible to recognize response also very early during radiochemotherapy.

关键词： PET esophageal cancer therapy response histomorphological regression early therapy e?ect

Pathohistological classification systems in gastric cancer:Diagnostic relevance and prognostic value

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World Journal of Gastroenterology 2014年第19期20卷 5679-5684页

作者： Felix Berlth Elfriede Bollschweiler Uta Drebber arnulf h hoelscher Stefan Moenig Department of General Visceral and Cancer SurgeryUniversity of Cologne50937 CologneGermany Department of Pathology University of Cologne50937 CologneGermany

Several pathohistological classification systems exist for the diagnosis of gastric cancer. Many studies have investigated the correlation between the pathohistological characteristics in gastric cancer and patient characteristics, disease specific criteria and overall outcome. It is still controversial as to which classification system imparts the most reliable information, and therefore, the choice of system may vary in clinical routine. In addition to the most common classification systems, such as the Laurén and the World health Organization (WhO) classifications, other authors have tried to characterize and classify gastric cancer based on the microscopic morphology and in reference to the clinical outcome of the patients. In more than 50 years of systematic classification of the pathohistological characteristics of gastric cancer, there is no sole classification system that is consistently used worldwide in diagnostics and research. however, several national guidelines for the treatment of gastric cancer refer to the Laurén or the WhO classifications regarding therapeutic decision-making, which underlines the importance of a reliable classification system for gastric cancer. The latest results from gastric cancer studies indicate that it might be useful to integrate DNA- and RNA-based features of gastric cancer into the classification systems to establish prognostic relevance. This article reviews the diagnostic relevance and the prognostic value of different pathohistological classification systems in gastric cancer.

关键词： Gastric cancer classification Lauré n World health Organization classification Pathohistology

Neoadjuvant chemoradiation changes podoplanin expression in esophageal cancer patients

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World Journal of Gastroenterology 2020年第23期26卷 3236-3248页

作者： Ute Warnecke-Eberz Patrick Plum Viola Schweinsberg Uta Drebber Christiane J Bruns Dolores T Müller arnulf h holscher Elfriede Bollschweiler Department of General Visceral and Cancer SurgeryUniversity Hospital of CologneCologne 50937Germany Department of Dermatology University Hospital of CologneCologne 50937Germany Institute of Pathology University Hospital of CologneCologne 50937Germany Agaplesion Markus hospital Frankfurt 60431Germany

BACKGROUND Locally advanced adenocarcinoma of the esophagus(EAC) and squamous cell carcinoma(ESCC) result in a worse prognosis. Neoadjuvant treatment improves survival, however, only for responders. The transmembrane glycoprotein podoplanin is overexpressed in squamous cell carcinomas, mi RNA-363 is associated to its regulation in head and neck *** To predict therapy response and prognosis markers, and targets for novel therapies would individualize treatments leading to more favourable *** Expression of podoplanin protein has been visualized by immunohistochemistry in surgical specimens of 195 esophageal cancer patients who underwent transthoracic esophagectomy: 90 ESCC and 105 EAC with clinical T2-3, Nx, *** hundred and six patients received neoadjuvant chemoradiation. RNA was extracted from paraffin-embedded tissue, and mi RNA-363 quantified by realtime Taq Man-real-time-PCR. D2-40 mab staining of > 5% was scored as high podoplanin expression(hPE). We related podoplanin and mi RNA-363 expression to histopathologic response after neoadjuvant treatment and clinicopathological characteristics, such as histological tumor type, survival rate or clinical tumor *** confirmed expression of membrane-bound podoplanin in 90 ESCC patients.26% showed hPE of > 5%. In addition, absence in EAC patients(only 2% with hPE) was shown. Lower podoplanin expression has been detected in resectionspecimen of 58 ESCC patients after neoadjuvant(RTx/CTx) treatment, only 11% with hPE, compared to 50% hPE of 32 non-pretreated primary surgery patients,P = 0.0001. This difference of podoplanin expression was confirmed comparing pre-treatment biopsies with matching post-treatment surgical specimens, P has been identified as a prognostic marker in 32 patients that underwent primary surgery without neoadjuvant treatment. Low(0-5%)podoplanin expression was associated with better prognosis compared to patients with hPE, P = 0.013. Podoplanin e

关键词： Esophageal cancer Response prediction Prognosis D2-40 Posttranscriptional regulation miRNA-363

Simultaneous occurrence of a hepatocellular carcinoma and a hepatic non-hodgkin's lymphoma infi ltration

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World Journal of hepatology 2010年第6期2卷 246-250页

作者： Sabine heidecke Dirk L Stippel arnulf h hoelscher Inga Wedemeyer hans-Peter Dienes Uta Drebber Department of General- Visceral- and Cancer Surgery University Hospital of Cologne Department of Pathology University Hospital of Cologne

To investigate the simultaneous occurrence of hepatocellular carcinoma and non-hodgkin's lymphoma, we report the case of a 70 year old patient with a primary diagnosis of non-hodgkin's lymphoma in 2002. In a routine follow up investigation of his chronic lymphocytic leukemia a newly detected mass in the Couinaud's segments 2 and 3 was found. No hepatitis C virus or hepatitis B virus infection or cirrhosis was evident. After laparoscopic segmentectomy the histological examination revealed a hepatocellular carcinoma. While the relation between liver parenchyma damages and hepatocellular carcinoma or non-hodgkin's lymphoma is well known, only a few publications have focused on the coexistence of hepatocellular carcinoma and non-hodgkin's lymphoma. With this case we demonstrate the coexistence of these diseases without having a pre- damaged liver parenchyma.

关键词： hepatocellular carcinoma Non-hodgkin’s lymphoma Etiology Carcinogenesis histology