Mia Hashibe

Cystectomy for bladder cancer: a contemporary series.

PURPOSEnTo validate the current TNM staging system, we analyzed our contemporary experience with 300 cystectomies.nnnMATERIALS AND METHODSnThe pathological material and medical records of 300 patients treated with cystectomy were reviewed, and the new TNM classification was adopted.nnnRESULTSnThe median followup of patients with no evidence of disease was 65 months, and overall survival rate was 45% with a median survival of 50 months. In a Cox regression analysis only patient age, pT stage and neoadjuvant chemotherapy were significant factors for survival. The disease specific survival was 67% with a median survival of 94 months. In a multiple proportional hazards analysis only pT stage and previous chemotherapy were significant factors of disease specific survival. A significant difference was seen in the overall and disease specific survival between patients with organ confined and nonorgan confined tumors. We did not observe a difference in the survival rate among patients with pT4a to pT3 tumors. Significant differences were not seen in survival rates between sexes or among patients of different age groups. Transitional cell carcinoma was the predominant histological type, and no significant difference was found in patient outcome among the different histological subtypes.nnnCONCLUSIONSnBladder cancer can be categorized into organ confined and nonorgan confined tumors. This dichotomous grouping is better suited for evaluating adjuvant clinical trials. The pT stage of the bladder and prostate should be prospectively analyzed together to better define the clinical implications of prostatic involvement. In our opinion the histological subtypes do not affect outcome.

Comparison of methods for DNA extraction from paraffin-embedded tissues and buccal cells

Both paraffin-embedded tissue specimens and buccal cells are excellent resources for large-scale molecular epidemiological studies. In order to identify the optimal method for DNA extraction, we compared three methods: (1) modified phenol-chloroform protocol; (2) simple boiling method; and (3) DNA Extraction Mini Kit. For paraffin-embedded tissue specimens, amplification of the beta-globin gene sequence was successful in 30 of 34 (88.2%) by the simple boiling method, 29 of 34 (85.3%) samples using DNA extracted by the phenol-chloroform method, and 18 of 34 (52.9%) by the DNA Mini Kit. For buccal cells, amplification of the beta-globin gene sequence was successful in 16 of 17 (94.1%) DNA samples extracted by the phenol-chloroform method, 2 of 16 (12.5%) by the simple boiling method, and 12 of 16 (75%) by the DNA Mini Kit. Both the simple boiling method and the phenol-chloroform method are better methods for DNA isolation from paraffin-embedded tissue specimens, and the phenol-chloroform method is the best method for DNA extraction from buccal cells.

Risk factors for multiple oral premalignant lesions

Oral leukoplakia, oral submucous fibrosis and erythroplakia are 3 major types of oral premalignant lesions. Multiple oral premalignant lesions may possibly develop due to field cancerization, where carcinogenic exposures can cause simultaneous genetic defects to the upper aerodigestive tract epithelium, putting the epithelium at high risk for development of premalignant lesions at different stages of carcinogenesis. There have been no epidemiological studies on risk or protective factors of the disease. A case‐control study was conducted with data from the baseline screening of a randomized oral cancer screening trial in Kerala, India. A total of 115 subjects with multiple oral premalignant lesions (8–10% of oral premalignant lesions in our case series) were included: 64 subjects with oral leukoplakia and oral submucous fibrosis, 19 subjects with oral leukoplakia and erythroplakia, 22 subjects with oral submucous fibrosis and erythroplakia and 10 subjects with all 3 lesions. Individuals without oral lesions were considered controls (n=47,773). The odds ratio (OR) for ever tobacco chewers was 37.8 (95% confidence interval (CI)=16.2–88.1) when adjusted for age, sex, education, BMI, smoking, drinking and fruit/vegetable intake. Dose‐response relationships were seen for the frequency (p<0.0001) and duration of tobacco chewing (p<0.0001) with the risk of multiple oral premalignant lesions. Whereas alcohol drinking may possibly be a risk factor for multiple oral premalignant lesions, smoking was not associated with the risk of multiple oral premalignant lesions (OR=0.9, 95%CI=0.5–1.7). The results suggest that tobacco chewing was the most important risk factor for multiple oral premalignant lesions and may be a major source of field cancerization on the oral epithelium in the Indian population.

Socioeconomic status, lifestyle factors and oral premalignant lesions.

Several studies have suggested that low socioeconomic status (SES) is associated with a higher risk of oral cancer, but the association with oral premalignant lesions has not yet been explored. The aim of this study was to examine the association of education, occupation, income and SES index with oral premalignant lesions. A case-control study was conducted with data from the baseline screening of a randomized oral cancer screening trial in Kerala, India. There were a total of 927 oral leukoplakia, 170 oral submucous fibrosis, 100 erythroplakia and 115 multiple oral premalignant lesion cases and 47,773 controls. Subjects with high SES index had protective ORs for oral premalignant lesions, ranging from 0.6 to 0.7, after adjustment for age, sex, BMI, tobacco chewing, smoking, drinking and fruit/vegetable intake. Higher education levels were also associated with decreased risk of all four oral premalignant lesions. Protective ORs for income were observed for oral leukoplakia and possibly oral submucous fibrosis and erythroplakia. SES may be associated with oral premalignant lesions because of access to medical care, health related behaviors, living environment or psychosocial factors. Though the mechanism for the association is not clear, higher SES index, education and income were associated with decreased risk of oral premalignant lesions in our study.

Alcohol drinking, body mass index and the risk of oral leukoplakia in an Indian population

Although tobacco habits have been associated with the risk of oral leukoplakia, alcohol drinking and body mass index (BMI) as risk factors have not been well established. The purpose of this study is to evaluate the independent effects of drinking, BMI, tobacco chewing and smoking on the risk of oral leukoplakia. A case‐control study was conducted, with data from an ongoing randomized oral cancer screening trial in Kerala, India. Trained health workers conducted interviews and performed oral visual inspections to identify oral premalignant lesions such as leukoplakia. The logistic regression model in SAS was used to estimate odds ratios (OR) and 95% confidence intervals (95% CI). A total of 927 leukoplakia cases and 47,773 controls were included in the analysis. Ever alcohol drinking was a significant risk factor for oral leukoplakia among nonsmokers (OR=2.1, 95%CI=1.3, 3.4) and non‐chewers (OR=1.8, 95%CI=1.3, 2.5) after adjusting for age, sex, education, BMI and tobacco habits. The association with alcohol drinking was stronger among women (OR=3.9, 95%CI=1.5, 10.4) than men (OR=1.5, 95%CI=1.3, 1.9). An inverse dose‐response relationship was observed between BMI and the risk of oral leukoplakia (p for trend=0.0075). Tobacco chewing was a stronger risk factor for women (OR=37.7, 95%CI=24.2, 58.7) than for men (OR=3.4, 95%CI=2.8, 4.1). Smoking was a slightly stronger risk factor for men (OR=3.3, 95%CI=2.5, 4.3) than for women (OR=2.0, 95%CI=1.5, 2.9). In conclusion, alcohol drinking was found to be an independent risk factor while BMI might be inversely associated with the risk of oral leukoplakia in an Indian population. Int. J. Cancer 88:129–134, 2000.

Marijuana smoking and head and neck cancer

A recent epidemiological study showed that marijuana smoking was associated with an increased risk of head and neck cancer. Among high school students and young adults, the prevalence of marijuana use was on the rise in the 1990s, with a simultaneous decline in the perception that marijuana use is harmful. It will be a major public health challenge to make people aware of the harmful effects of marijuana smoking, when some people view it as the illicit drug with the least risk. The carcinogenicity of Δ9‐tetrahydrocannabinol (THC) is not clear, but according to laboratory studies, it appears to have antitumor properties such as apoptosis as well as tumor‐promoting properties such as limiting immune function and increasing reactive oxygen species. Marijuana tar contains similar carcinogens to tar from tobacco cigarettes, but each marijuana cigarette may be more harmful than a tobacco cigarette since more tar is inhaled and retained when smoking marijuana. More molecular alterations have been observed in bronchial mucosa specimens of marijuana smokers compared to nonsmokers. Field cancerization may be occurring on the bronchial epithelium due to marijuana smoking exposure. Several case studies were suggestive of an association of marijuana smoking with head and neck cancers and oral lesions. However, in a cohort study with 8 years of follow‐up, marijuana use was not associated with increased risks of all cancers or smoking‐related cancers. Further epidemiological studies are necessary to confirm the association of marijuana smoking with head and neck cancers and to examine marijuana smoking as a risk factor for lung cancer. It will also be of interest to examine potential field cancerization of the upper aerodigestive tract by marijuana and to explore marijuana as a risk factor for oral premalignant lesions.

Body mass index, tobacco chewing, alcohol drinking and the risk of oral submucous fibrosis in Kerala, India

Objective: While chewing areca nut is considered a risk factor for oral submucous fibrosis, the effects of cigarette smoking, alcohol drinking, and body mass index (BMI) have not been examined; nor are they well established. In this study we investigated the association between BMI, smoking, drinking, and the risk of oral submucous fibrosis. Methods: We conducted a case–control study within the fraåework of an ongoing randomized oral cancer screening trial in Kerala, India. Trained health workers conducted interviews with structured questionnaires and oral visual inspections to diagnose oral premalignant lesions. A total of 170 oral submucous fibrosis cases (139 women and 31 men) and 47,773 controls were identified. The odds ratios (OR) and 95% confidence intervals (CI) were calculated by logistic regression in SAS. Results: The adjusted OR for ever-tobacco chewing was 44.1 (95% CI = 22.0–88.2). An inverse dose–response relationship was seen between BMI and the risk of oral submucous fibrosis when both genders were combined (p for trend = 0.0010), with an OR of 0.5 (95% CI = 0.3–0.9) for the highest BMI quartile compared to the lowest. Alcohol drinking may possibly be associated with the risk of oral submucous fibrosis; the adjusted OR for ever drinking was 2.1 (95% CI = 1.0–4.4). Cigarette smoking did not appear to be a risk factor for women or for men. Both smoking and drinking were rare habits among women. Conclusion: This study suggested, for the first time, that BMI was inversely associated with the risk of oral submucous fibrosis for both genders when potential confounding factors were adjusted. Our results indicated that alcohol drinking might be a moderate risk factor and confirmed the previous observation that chewing tobacco was a strong risk factor for oral submucous fibrosis.