Esophageal cancer : Evaluation of some new strategies

Abstract: Objective:To study and to evaluate new strategies regarding the diagnosis, treatment and nutrition of esophageal cancer patients. Methods: A background retrospective analysis of the files of all 1284 esophageal cancer patients in Stockholm County 1978 - 1995 was performed and followed by a multicenter study of the development and evaluation of a cisplatinum based chemoradiation protocol for the treatment of nonmetastatic squamous cell carcinoma of the esophagus. An immunohisto-chemistry analysis of prechemoradiation biopsies from patients with squamous cell carcinoma of the esophagus regarding the expression of factor VIII, CD-34, p53and bcl-2 and DNA ploidy was described. The results were correlated to tumor response. A method to register local spread of tumor in the esophageal wall through serial endoscopic fine needle aspirations (FNA). FNA was also evaluated as a diagnostic tool and the cytologic morphology was correlated to survival. Finally the technical aspects and risks of using percutaneous endoscopic gastrostomy (PEG) in a consecutive series of patients with esophageal cancer were evaluated. Results: A significant improvement in survival was found during 1978-1995. No survival benefit was noted for patients operated in high volume clinics. An increase in the incidence of adenocarcinomas among men was documented. Chemoradiation toxicity was mainly attributable to hematological impairment and lead to two adjustments of the treatment protocol (addition of filgrastim and lowering of the 5-fluorouracil dose). These changes made it possible to give the planned treatment to a gradually higher proportion of the patients. No correlations were found between the expressions of p53, bcl-2 or DNA ploidy and tumor response to chemoradiation. In spite of significant correlations to the markers for angiogenesis this significance may have been questionable since factor VIII had a positive and CD- 34 a negative correlation to tumor response. In the FNA study a high proportion of patients had malignant cells in the esophageal wall at a considerable distance from macroscopic tumor. When the quotas between numbers of benign and malignant cells in tumor aspirates were evaluated, patients with a high quota had a median survival of 9.7 months while patients with low quota had a median survival of 23.2 months. (p<0.03). PEGs were successfully inserted in 97% after dilatation in 46 %. The procedure related mortality was 0.9%. The right gastroepiploic artery was injured by the PEG in one surgical patient. 1 possible implantation metastasis was found. Conclusions: Survival has increased among esophageal cancer patients in Stockholm County. The number of yearly esophageal cancer operations performed in a clinic did not correlate to long term survival. The chemoradiation protocol resulted in a combination of a high proportion of complete responses and, after protocol adjustments, a good compliance. The relapse pattern following chemoradiation showed that further development of the systemic part, i.e. chemotherapy, of the protocol might be beneficial. It was not possible to predict tumor response to the chemoradiation protocol studied through the analysis of pretreatment expression of p53, bcl-2 or DNA ploidy in biopsy specimens. In spite of significant correlations between complete tumor responses and the expressions of the markers for angiogenesis this significance may have been questionable since factor VIII had a positive and CD-34 a negative correlation to tumor response. Serial FNA could demonstrate local microscopic tumor spread in the wall of the esophagus in vivo in esophageal cancer patients. There may have been a correlation between the quota of benign/malignant cells in tumor aspirates in FNA and survival giving patients with a low quota a more favorable prognosis. PEG is a safe and a well tolerated way of ensuring enteral nutrition in patients with esophageal cancer.