Impact of External Beam Radiotherapy after Surgical Resection for Hilar Bile Duct Carcinoma

PURPOSE: For bile duct carcinomas, local treatment including surgical resection plays an important role. In the case of hilar bile duct carcinoma, the rate of resection is low and local recurrences are frequent, even after radical resection. Radiotherapy, one of the local remedies, may influence the treatment result. The aims of this study were to determine the effect of radiotherapy after surgical resection on the length of survival, as well as the radiation toxicity, in patients with hilar bile duct carcinoma. METHODS: Seventy patients with hilar bile duct carcinoma were included in this study; 46 underwent surgical resection only while 24 additionally received external beam radiotherapy after resection. The authors compared the survival rate between the two groups and investigated the complications following radiotherapy. RESULTS: The overall 5-year survival rate after surgical resection was 28.3%; 20.1% and 31.3% in patients with and without radiotherapy, respectively. The difference was not significant (P> 0.10). In patients with positive surgical margin, the 5-year survival rate for the radiation group was superior to that of the non-radiation group (21.8% vs. 10.1%), but aqain the difference was not statistically significant (P> 0.10). In patients with lymph node metastasis the survival rates for radiation and non-radiation groups showed no significant difference(median survival, 7 vs. 13 months) (P> 0.10). Leukopenia (n=2) and digestive complications including gastroduodenal ulcers (n=2) occurred after radiotherapy. CONCLUSION: External beam radiotherapy after radical resection had no significant effect on the length of survival in patients with resectable hilar bile duct carcinomas.

Microsatellite Instability and Overexpression of p53 Protein in Human Gastric Carcinomas: Clinicopathologic Implications and Prognosis

PURPOSE: Striking advances in molecular analysis of human gastrointestinal cancer indicate that malignant transformation of normal epithelial cells is necessary for a multiple process associated with an accumulation of multiple gene abnormalities affecting DNA repair genes, oncogenes, and tumor suppressor genes. Microsatellites are short repeated DNA sequences scattered throughtout the human genome. Microsatellite instability (MSI) may underlie the etiology of mutistep gastric carcinogenesis. The altered microsatellites observed in tumors with DNA replication error (RER) phenotypes may represent the expression of such an instability. METHODS: Fourty-four gastrectomy specimens from patients with gastric carcinomas were examined in an attempt to study the molecular mechanisms of gastric carcinogenesis, to assess the prognostic value of genetic instability and mutant p53 protein expressions, and to evaluate a possible interaction between genetic instability and mutation of the p53 protein. Pairs of tumor and adjacent normal tissue were amplified at six microsatellite loci, and their sizes were compared. Tumors with microsatellite sizes different from their normal tissue sizes for at least two of the tested loci were designated as MSI. Mutations of the p53 protein were investigated with immunohistochemical staining. RESULTS: MSI was detected in 33.3% of the early gastric carcinomas and in 41.4% of the advanced gastric carcinomas with an overall frequency of 38.6%. The frequency of MSI tended to occur more frequently in poorly differentiated adenocarcinomas. The frequency of MSI was not significanctly different with repect to age, sex, size of tumor, location of tumor, depth of invasion,lymph-node metastasis, and Helicobacter pylori infection. Mutation of the p53 protein was detected in 40.0% of the early gastric carcinomas and in 48.3% of the advanced gastric carcinomas with an overall frequency of 45.5%. Mutation of the p53 protein occurred more frequently in positive lymph-node metastasis and advanced stage. There were no correlations between microsatellite instability and p53 expression.The overall 5-year surval rate was 56.6%. The 5-year survival rate of patients with MSI was 58.5%, and that for patient with mutant p53 protein was 42.8%. Gastric cancers with MSI showed a relatively good prognosis, but the result was not statistically significant (p=0.976), and patients with mutant p53 protein had a statistically significant poorer prognosis (p=0.049). CONCLUSION: These findings suggest that both MSI and mutation of the p53 protein are present in early and later stages of malignant transformation. Based on this study, investigations with a larger number of patients are needed to establish their roles as prognostic indicators in gastric cancer.

Long-term Result of Radical Resection for Hilar Bile Duct Cancer

Sixty patients with hilar bile duct cancer were operated on during a period of nine years. The tumor was resected in 45 patients (resection rate:75.0%). A hilar resection with regional lymph-node dissection was performed in 27 patients, and various types of hepatic resections were added in 18 patients. A potentially curative resection was achieved in 20 patients (curative resection rate:44.4%). There were two operative deaths (operative mortality:4.4%). The overall cumulative five-year survival rate was 25.6%. Six patients survived for more than five years. The survival was superior in patients with a curative resection and in those with a combined hepatic resection, but this result was statistically insignificant. Regional lymph-node metastasis, gross type, histologic grade, and perineural invasion were significant prognostic factors. We conclud that improved survival in hilar bile duct cancers can be achieved by a radical resection with acceptable morbidity and mortality.