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Molecular Biology of Esophageal Cancer

The Chinese-German Journal of Clinical Oncology 2004年第4期3卷 205-209页

作者： HuanXi JanBrabender ralfmetzger PaulM.Schneider DepartmentofVisceral-andVascularSurgery UniversityofCologneCologneGermany／／DepartmentofGeneralSurgeryBeijingHospitalBeijingChina DepartmentofVisceral-andVascularSurgery UniversityofCologneCologneGermany

There have been many new developments in our understanding of esophageal carcinoma biology over the past several years. Information regarding both of the major forms of this disease, adenocarcinoma and squamous cell carcinoma, has accumulated in conjunction with data on precursor conditions such as Barrett’s esophagus. Interesting and promising ?ndings have included overexpression of proto-oncogenes, loss of heterozygosity at multiple chromosomal loci, tumor suppressor gene inactivation, epigenetic silenc- ing by DNA methylation, and mutations and deletions involving the tumor suppressor gene p53. Important cancer pathways, the cyclin kinase inhibitor cascade and the DNA mismatch repair process, implicated in the genesis of multiple tumor types have also been inculpated in esophageal carcinogenesis. Alterations in the p16 and p15 cyclin kinase inhibitors including point mutations and homozygous deletions have been reported in primary esophageal tumors. Further developments in the ?eld of molecular carcinogen- esis of esophageal malignancies promise to yield improvements in prevention, early detection, prognostic categorization, and perhaps gene-based therapy of this deadly disease.

关键词： esophageal cancer molecular biology

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Neoadjuvant Treatment for Esophageal Cancer

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The Chinese-German Journal of Clinical Oncology 2004年第4期3卷 249-252页

作者： PaulM.Schneider HuanXi StephanE.Baldus JanBrabender ralfmetzger DepartmentofVisceral-andVascularSurgery UniversityofCologneCologneGermany DepartmentofGeneralSurgery BeijingHospitalBeijingChina InstituteofPathology UniversityofCologneCologneGermany

Because the con?icting data currently available from the performed randomized trials it is very di?cult to provide strict guidelines for the treatment of patients with locoregional advanced esophageal cancers. Surgery however, remains the standard of care for potentially resectable disease. Preoperative chemotherapy is still controversial with two large randomized trials resulting in two di?erent conclusions regarding the survival bene?t. Preoperative chemoradiation is also controversial since only one randomized trial showed a clear survival bene?t however, the patients treated with surgery alone in this trial had an unusually poor outcome. And the study by Urba et al was not powered enough to show a clear survival bene?t for patients treated with neoadjuvant chemoradiation. The results of three metaanalysis of these randomized studies show lower rate of resection, higher rate of R0-resection, more often postoperative mortality and better prognosis for patients with neoadjuvant radiochemotherapy. As a consequence one may consider o?ering neoadjuvant chemotherapy or neoadjuvant radiochemotherapy to patients with locally- advanced disease under the premise that patients have a good performance status and understand the controversies about this therapeutic option. Larger trials with su?cient power to clearly detect survival bene?ts for patients treated with neoadjuvant chemotherapy or radiochemotherapy are necessary before this therapeutic option will be the standard of care.

关键词： esophageal cancer neoadjuvant treatment

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Prediction of Response to Multimodality Treatment inEsophageal Cancer

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The Chinese-German Journal of Clinical Oncology 2004年第4期3卷 253-256页

作者： ralfmetzger HuanXi FutoshiMiyazono HiroshiHigashi UteWarnecke-Eberz StephanE.Baldus JanBrabender PaulM.Schneider DepartmentofVisceral-andVascularSurgery UniversityofCologneCologneGermany DepartmentofGeneralSurgery BeijingHospitalBeijingChina FirstDepartmentofSurgery UniversityofKagoshimaSchoolofMedicineKagoshimaJapan InstituteofPathology UniversityofCologneCologneGermany

Patients with locally advanced esophageal cancer have a dismal prognosis when treated exclu- sively by surgery. This fact prompted many investigators to apply neoadjuvant treatment strategies in an e?ort to improve survival. Results from phase III randomized trials are encouraging however, they revealed 五笔字型计算机汉字输入技术 that only patients with major histopathological response will bene?t from treatment. Therefore, predic- tive molecular markers indicating response or non-response to neoadjuvant treatment would be extremely helpful in selecting patients for current and future treatment protocols. In this paper we review the role of the molecular markers ERCC1 (excision repair cross-complementing 1 gene) and c-erbB-2 (synonym: HER2/neu) in predicting response to radiochemotherapy and outcome for patients with locally advanced resectable esophageal cancers (cT2-4, Nx, M0). The results are promising and it appears that we might expect to unequivocally identify with ERCC1 and c-erbB-2 respectively, approximately up to one third of patients who ful?l the criteria for neoadjuvant treatment for locally advanced esophageal cancer but will not bene?t from our treatment protocol. Integration of such markers in the clinical setting might prevent a substantial number of patients from expensive, non-e?ective and potentially harmful therapies, and could lead to a more individualized type of combined multimodality treatment in the near future.

关键词： esophageal cancer response prediction multimodality therapy neoadjuvant radiochemotherapy ERCC1 c-erbB-2

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