Publications (7)30.17 Total impact
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Article: EGF61 polymorphism predicts complete pathologic response to cetuximab-based chemoradiation independent of KRAS status in locally advanced rectal cancer patients.
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ABSTRACT: Cetuximab has shown significant clinical activity in metastatic colon cancer. However, cetuximab-containing neoadjuvant chemoradiation has not been shown to improve tumor response in locally advanced rectal cancer patients in recent phase I/II trials. We evaluated functional germline polymorphisms of genes involved in epidermal growth factor receptor pathway, angiogenesis, antibody-dependent cell-mediated cytotoxicity, DNA repair, and drug metabolism, for their potential role as molecular predictors for clinical outcome in locally advanced rectal cancer patients treated with preoperative cetuximab-based chemoradiation. 130 patients (74 men and 56 women) with locally advanced rectal cancer (4 with stage II, 109 with stage III, and 15 with stage IV, 2 unknown) who were enrolled in phase I/II clinical trials treated with cetuximab-based chemoradiation in European cancer centers were included. Genomic DNA was extracted from formalin-fixed paraffin-embedded tumor samples and genotyping was done by using PCR-RFLP assays. Fisher's exact test was used to examine associations between polymorphisms and complete pathologic response (pCR) that was determined by a modified Dworak classification system (grade III vs. grade IV: complete response). Patients with the epidermal growth factor (EGF) 61 G/G genotype had pCR of 45% (5/11), compared with 21% (11/53) in patients heterozygous, and 2% (1/54) in patients homozygous for the A/A allele (P < 0.001). In addition, this association between EGF 61 G allele and pCR remained significant (P = 0.019) in the 59 patients with wild-type KRAS. This study suggested EGF A+61G polymorphism to be a predictive marker for pCR, independent of KRAS mutation status, to cetuximab-based neoadjuvant chemoradiation of patients with locally advanced rectal cancer.Clinical Cancer Research 06/2011; 17(15):5161-9. · 7.74 Impact Factor -
Article: Prognostic relevance of demographics and surgical practice for patients with gastric cancer in two centers: in Poland versus Germany.
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ABSTRACT: Although studies comparing the surgical treatment of gastric carcinoma in Japan and Western industrialized countries have revealed differing survival rates, no studies to date have been performed comparing Western and Eastern Europe. This study aimed to compare demographics and surgical practice as well as the related prognostic impact on gastric cancer patients treated in Poland and Germany. This retrospective study included gastric cancer patients treated between 1999 and 2004 by surgical departments in Gdansk (Poland) and Cologne (Germany). Univariate and multivariate analyses of demographic, histopathological, surgical, and prognostic data were performed. Included were 117 patients from Gdansk and 130 patients from Cologne. The Cologne patients showed higher incidence rates of serious comorbidity, pT1 cancer, and distant metastasis than those from Gdansk. Indications for and frequency of selected surgical procedures differed significantly. D2-lymphadenectomy was performed in 89% of the Cologne patients, while D1-lymphadenectomy was done for 85% of the Gdansk patients. Univariate analysis yielded a 5-year survival rate of 28.3% for the Gdansk patients, and 40.3% for the Cologne patients (p = 0.056). Independent prognostic factors were pT category (p = 0.002), pN category (p < 0.001), pM category (p = 0.027), residual tumor (R) category (p = 0.004), age (p = 0.012), and number of resected lymph nodes (p = 0.005). Significant differences of clinical and surgical parameters exist between gastric cancer patients treated in Poland and Germany. In addition to established independent prognostic factors, we found that survival improved with each additionally resected lymph node.Gastric Cancer 03/2011; 14(3):234-41. · 2.42 Impact Factor -
Article: High expression of heparanase is significantly associated with dedifferentiation and lymph node metastasis in patients with pancreatic ductal adenocarcinomas and correlated to PDGFA and via HIF1a to HB-EGF and bFGF
Gastroenterology 01/2008; 134(4):A856-A856. · 11.68 Impact Factor -
Article: COX-2 mRNA expression is significantly increased in acid-exposed compared to nonexposed squamous epithelium in gastroesophageal reflux disease.
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ABSTRACT: Little is known about the role of cyclooxygenase (COX)-2 in gastroesophageal reflux disease (GERD) and the development of Barrett's metaplasia. The objectives of this study were to further analyze COX-2 mRNA expression in patients with GERD compared to Barrett's esophagus (BE) and Barrett's cancer (BC). Tissue samples from 110 patients with GERD (n = 43), BE (n = 20), and BC (n = 47) were obtained in routine upper GI endoscopy. Expression levels of COX-2 were measured by quantitative real-time reverse trancriptase polymerase chain reaction (RT-PCR). Also, 24-h pH monitoring was performed in all patients of the GERD study group and the DeMeester composite score was used to match COX-2 mRNA expression with the severity of acid exposure in the lower esophagus. COX-2 mRNA is progressively upregulated within the metaplasia-dysplasia-adenocarcinoma (MDA) sequence (p = 0.001). COX-2 levels of the squamous epithelium in the distal esophagus from patients with GERD and a pathologic mean DeMeester score (>14.72) were significantly higher than in patients with normal DeMeester scores (p = 0.01). In summary our findings suggest that alterations in COX-2 mRNA expression occur independently of endoscopic or histologic signs of GERD in the acid-exposed squamous epithelium of the distal esophagus. However, this early COX-2 increase in GERD is further upregulated within the MDA sequence for yet unknown reasons.Journal of Gastrointestinal Surgery 10/2007; 11(9):1105-11. · 2.83 Impact Factor -
Article: Splenic rupture: an unusual complication of colonoscopy: case report and review of the literature.
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ABSTRACT: Splenic rupture after colonoscopy is rare. Only 44 cases previously have been reported in the English literature. Partial capsular avulsion is the proposed mechanism of injury. Any condition causing increased splenocolic adhesions may be a predisposing factor to splenic injury. One case of splenic injury after colonoscopy is reported in addition to a complete review of the literature.Surgical laparoscopy, endoscopy & percutaneous techniques 11/2006; 16(5):351-4. · 1.23 Impact Factor -
Article: Sex differences in the predictive power of the molecular prognostic factor HER2/neu in patients with non-small-cell lung cancer.
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ABSTRACT: Recent studies imply that HER2/neu is a potential prognostic factor in patients with non-small-cell lung cancer (NSCLC). Whereas considerable evidence indicates sex differences in epidemiologic, hormonal, biologic, and genetic factors in this disease, it has remained unknown whether HER2/neu has a diverse function as a prognostic factor in men and women. We investigated the association between gene expression levels of HER2/neu in the primary tumors of 90 patients with curable resected NSCLC and survival, especially analyzing whether there is a different potential of this molecular factor in its prognostic impact between men and women. High HER2/neu gene expression levels were found in 62 patients (68.9%), and low HER2/neu gene expression levels were found in 28 patients (31.1%). High HER2/neu messenger RNA expression levels were associated with inferior survival (P = 0.09) compared with lower HER2/neu expression. Survival analysis was then carried out separately for men and women in this group of patients. An HER2/neu gene expression cutoff point was identified that separated women, but not men, into good and poor prognostic groups. These findings suggest that HER2/neu as a prognostic factor is strongly sex specific, indicating that it is not useful for men but highly predictive for women.Clinical Lung Cancer 04/2006; 7(5):332-7. · 2.94 Impact Factor -
Article: Evaluation of POSSUM scoring system in patients with gastric cancer undergoing D2-gastrectomy.
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ABSTRACT: Risk adjustment and stratification play an important role in quality assurance and in clinical research. The Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity (POSSUM) is a patient risk prediction model based on 12 patient characteristics and 6 characteristics of the surgery performed. However, because the POSSUM was developed for quality assessment in general surgical units, its performance within specific subgroups still requires evaluation. The aim of the present study was to assess the accuracy of POSSUM in predicting mortality and morbidity in patients with gastric cancer undergoing D2-gastrectomy. 137 patients with gastric cancer undergoing gastrectomy were included in this study. Detailed, standardized risk assessments and thorough documentation of the post-operative courses were performed prospectively, and the POSSUM scores were then calculated. The 30- and 90-day mortality rates were 3.6% (n = 5) and 5.8% (n = 8), respectively. 65.7% (n = 90) of patients had normal postoperative courses without major complications, 14.6% (n = 20) had moderate and 13.9% (n = 19) had severe complications. The number of mortalities predicted by the POSSUM-Mortality Risk Score (R1) was double the actual number of mortalities occurring in the median and high-risk groups, and was more than eight times the actual number of mortalities occurring in the low-risk group (R1 < 20%). However, the calculated R1 predicted rather well in terms of severe morbidity or post-operative death in each risk group: in predicted low risk patients the actual occurrence rate (AR) of severe morbidity or post-operative death was 14%, for predicted medium risk patients the AR was 23%, and for predicted high risk patients the AR was 50% (p < 0.05). The POSSUM-Morbidity Risk Score (R2) overestimated the risk of morbidity. The POSSUM Score may be beneficial and can be used for assessment of the peri- and post-operative courses of patients with gastric carcinoma undergoing D2-gastrectomy. However, none of the scores examined here are useful for preoperative prediction of postoperative course.BMC Surgery 01/2005; 5:8. · 1.33 Impact Factor
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2005
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Universität Köln
- Department of Vascular Surgery
Köln, North Rhine-Westphalia, Germany
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