retinamide and Esophageal-Neoplasms

To report long term therapeutic effect in patients with esophageal pre-cancerous lesions in high-risk area of esophageal cancer.. The therapeutic trial enrolled 2,531 cases of severe dysplasia and 3,393 cases of mild dysplasia. A 2-arm randomized, placebo-controlled design was used in which the participants received Zeng Sheng Ping (ZSP, an herbal composite), retinamide or placebo for cases with severe dysplasia and riboflavin or placebo for those with mild dysplasia.. Treatment with ZSP and retinamide decreased malignant transformation rate of severe dysplasia by 52.2% and 43.2%, respectively after 5 years of treatment. When the treatment had been discontinued for 4 years, the rate of malignat transformation was decreased by 42.1% and 38.2% respectively, which remained significantly higher than that of the placebo-treated control. Riboflavin treatment was continued for 9 years. At the end of 5-year medication, the malignant transformation rate decreased by 34.8%, which was not significantly different from that of the placebo control. When the treatment was continued up to 9 years, the rate was further decreased to 37.0%, which became statistically significant.. ZSP, retinamide and riboflavin treatment can effectively prevent esophageal dysplasia from transforming into carcinoma.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Drugs, Chinese Herbal; Esophageal Neoplasms; Female; Humans; Male; Middle Aged; Precancerous Conditions; Tretinoin

Since 1983, a long-term clinical trial of esophageal carcinoma chemoprevention has been conducted in a high-risk area in China. From this study, 25 esophageal severe dysplasia patients without therapy were selected for analysis. After 5-year follow-ups, 14 cases progressed to esophageal carcinoma, while the other 11 cases remained stable. Three Papanicolaou's smears were used for each case, including one from the esophageal cytological examination at the beginning, two from the re-examinations three and five years later respectively. About 100 visually normal intermediate cells were randomly collected per slide by high resolution image analysis. More than 100 features (morphologic, densitometric, textural) were extracted. The classifications were made by means of stepwise linear discriminate analysis at the single cell level as on the specimen level using up to ten features. In all three comparisons of patients with progression and with regression at time of diagnosis, three years after diagnosis and five years later, the correct cell classification rates were about 70%. The subsequent specimen classifications by means of the a posteriori probability (APOP) distribution of the cells in each case led to 80% correct classification. All selected features reflected the chromatin structure of nuclei. The result demonstrated that the chromatin structures of esophageal epithelial cells in severely dysplasic patients are different between cases with and without progression. These results suggest the possibility of the application of image analysis in the clinical trials to find the dysplasia patients with higher risk of progression, in order to reduce the number of patients for therapy.

Topics: Adult; Aged; Antineoplastic Agents; Biomarkers, Tumor; Cell Nucleus; Chromatin; Cytodiagnosis; Drugs, Chinese Herbal; Esophageal Neoplasms; Esophagus; Humans; Image Processing, Computer-Assisted; Middle Aged; Prognosis; Prospective Studies; Time Factors; Tretinoin

Since 1983, we have been conducting inhibitory therapy for precancerous lesions of the esophagus in two regions of Henan Province considered high-risk areas of esophageal carcinoma. Our goal was to effect a 50% reduction in the canceration rate of marked esophageal dysplasia. By means of a cytological survey, 2531 cases of marked esophageal dysplasia and 3393 cases of mild esophageal dysplasia were selected. The former were randomly divided into 3 groups for antitumor-B (ATB, a mixture of Chinese herbs), retinamide (4-ethoxycarbophenylretinamide) and placebo treatment respectively, and the latter into 2 groups treated with riboflavin and placebo respectively. Treatment was continued for 3 or 5 years (administration rate greater than 90% in all groups) and esophageal cytology reexamined (reexamination rates were 94.1% and 92.5% respectively). Our results were as follows: 1) ATB 3- and 5-year subjects saw the canceration rate of marked esophageal dysplasia drop by 52.2% and 47.3% respectively as compared to control (P less than 0.01). 2) Retinamide lowered the canceration rate by 37.3% after a 3-year treatment period, with this reduction reaching 43.2% after an additional 2 years of treatment with increased dosages (P less than 0.05, P less than 0.01). 3) In the riboflavin group, the canceration rate of mild esophageal dysplasia was reduced by 22.2% and 34.8% after 3 and 5 years of treatment respectively, but these differences were not statistically significant. The above results verify the efficacy of medicamentous inhibitory therapy for esophageal precancerous lesions.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Drugs, Chinese Herbal; Esophageal Neoplasms; Female; Humans; Male; Middle Aged; Precancerous Conditions; Riboflavin; Tretinoin

9633 subjects aged 40 to 65 were sampled from high-risk areas for esophageal cancer and examined by esophageal exfoliative cytology. 2531 and 3393 cases of markedly and mildly dysplastic patients were screened out respectively. Those with marked dysplasia were randomized into 3 groups and given respective medications: antitumor B (Chinese herbs), 4-ethoxycarbophenylretinamide (retinamide) and placebo. The subjects with mild dysplasia were randomly divided into 2 groups for riboflavin and placebo treatment. After medication for 3 or 5 years the subjects were reexamined by esophageal exfoliative cytology. The incidence of esophageal cancer in the antitumor B group after taking medication for 3 and 5 years was reduced by 52.2% and 47.3% respectively as compared with the placebo group. These differences were statistically significant (chi 2 = 8.9115, P less than 0.01; chi 2 = 10.9573, P less than 0.01). The incidence of esophageal cancer in the retinamide group after 3 years of medication was reduced by 37.3% as compared with control, while the incidence among patients treated for 5 years dropped by 43.2% relative to control. This difference was statistically significant (chi 2 = 9.2836, P less than 0.01). The incidence of esophageal cancer in the riboflavin group was reduced by 22.2% and 34.8% respectively. The above results indicate that secondary prevention of esophageal cancer is possible and that inhibitory therapy of precancerous lesions of the esophagus is effective in preventing esophageal cancer. This method needs further trial and study in high risk areas of esophageal cancer. The reliability of the experimental results is critically discussed.

Topics: Adult; Aged; Antineoplastic Agents, Phytogenic; Drugs, Chinese Herbal; Esophageal Neoplasms; Female; Follow-Up Studies; Humans; Male; Middle Aged; Precancerous Conditions; Riboflavin; Tablets; Tretinoin

In 1983, intervention of precancerous lesion of esophagus was undertaken in the high risk area of esophageal cancer, Heshun Village, Linxian County. It had been expected that cancerous degeneration rate of esophageal dysplasia should be reduced by 50% so as the prevention of esophageal cancer could become possible. 6758 subjects of the general population aging from 40 to 65 were examined by esophageal exfoliative cytology, 1729 had marked dysplasia and 2411 had mild dysplasia of esophageal epithelium. Those with marked dysplasia were randomized into 3 groups to take their respective medication: antitumor B (Chinese herbs); retinamide (4-Ethoxycarbophenylretinamide) and placebo. The subjects with mild dysplasia were divided randomly into 2 groups for treatment by riboflavin and placebo. 95% of the subjects had taken 90% or more of the total medication for 3 years, at the end of which they were reexamined by esophageal exfoliative cytology. The reexamination rate was 94.1%. The incidence of esophageal cancer in the antitumor B group (3.9%) was reduced by 53% as compared with that of the placebo group (8.3%). This difference had statistical significant (means 2 = 7.672, P less than 0.05). The incidence of esophageal cancer in retinamide and riboflavin groups were reduced by 33.7% and 19% as compared with those of the control groups. The regression rate of dysplasia in the treatment groups were increased than that of the control groups. The above results showed that our hypothesis about the secondary prevention of esophageal cancer is correct. The intervention of precancerous lesion of the esophagus is effective in the prevention of esophageal cancer.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Drugs, Chinese Herbal; Esophageal Neoplasms; Female; Humans; Hyperplasia; Male; Middle Aged; Precancerous Conditions; Riboflavin; Tretinoin