Kalble T.; Otto T.
Abt. fur Urologie und Poliklinik, Chirurgisches Zentrum, Universitat Heidelberg, Im N euenheimer Feld 110, D-69120 Heidelberg Germany
Urologe Ausg. A (Germany), 1994, 33/6 (553-556)

Several unconventional agents or methods are used for recurrence prophylaxis of superficial bladder cancer. In animal experiments KLH (keyhole limpet hemocyanin) has shown an effect comparable to that of BCG on bladder carcinoma, resulting in an increase of natural killer cell activity. The few clinical data dealing with KLH are contradictory. A prospective randomized study with a large number of patients uniform high dosage and early start of instillation has not yet been performed for definitive evaluation of the clinical role of KLH. Whether mistletoe extracts or intravesical antineoplastic iontophoresis can prevent recurrence is not yet known. Vitamin A and megadose multivitamins in combination with intravesical BCG significantly decrease the recurrence rate. The most effective vitamin or the most important combination has not yet been identified, and the precise mechanism of action is also unknown.

Momas I.; Daures J.-P.; Festy B.; Bontoux J.; Gremy F.
Lab. d'Hygiene et de Sante Publique, Fac. Scis. Pharmaceutiques/Biol., 4 Avenue de l'Observatoire, 75270 Paris Cedex 06 France
Cancer Causes Control (United Kingdom), 1994, 5/4 (326-332)

In the Mediterranean region of France where bladder cancer mortality and incidence are high, a case-control study with 219 male incident cases and 794 randomized, male population-controls was carried out in 1987-89 to investigate bladder cancer risk factors and more specifically, regional factors. A stepwise logistic regression was applied to the data. This investigation confirms the role of tobacco and of certain occupational exposures in bladder carcinogenesis. There was a significant dose-response relationship with lifelong coffee drinking and alcohol consumption; however the risk estimates were only significantly elevated for the heaviest drinkers. The intake of saccharin was not associated with risk of bladder cancer. Infrequent consumption of carrots, spinach, and marrows conferred an increased risk, suggesting a protective effect of vitamin A. Finally, this investigation results in some new hypotheses. The study of residences and birthplaces has revealed a lower risk for those who have lived in a non-Mediterranean area and a higher risk for those born in a Mediterranean area. These features might be explained by some Mediterranean dietary habits, such as a high consumption of spices (odds ratio = 3.64, 95 percent confidence interval = 2.21-5.98).

Lamm D.L.; Riggs D.R.; Shriver J.S.; VanGilder P.F.; Rach J.F.; DeHaven J.I.
Department of Urology, West Virginia University, P.O. Box 9251, Morgantown, WV 26506 USA
J. Urol. (USA), 1994, 151/1 (21-26)

Epidemiological and laboratory studies suggest that vitamin supplements may be helpful in the prevention of some cancers but clinical trials to date have failed to demonstrate protection with naturally occurring vitamins. Without substantiation of the highly touted benefits of vitamins, few physicians who care for cancer patients have recommended their use. A total of 65 patients with biopsy confirmed transitional cell carcinoma of the bladder enrolled in a randomized comparison of intravesical bacillus Calmette-Guerin (BCG) with or without percutaneous administration was also randomized by closed envelope to therapy with multiple vitamins in the recommended daily allowance (RDA) versus RDA multivitamins plus 40,000 units vitamin A, 100 mg. vitamin B6, 2,000 mg. vitamin C, 400 units vitamin E and 90 mg. zinc. The addition of percutaneous BCG did not significantly lessen tumor recurrence but recurrence after 10 months was markedly reduced in patients receiving megadose vitamins. The 5-year estimates of tumor recurrence are 91% in the RDA arm and 41% in the megadose arm (p = 0.0014, Mantel-Cox). Overall recurrence was 24 of 30 patients (80%) in the RDA arm and 14 of 35 (40%) in the high dose arm (p = 0.0011, 2-tailed Fisher's exact test). Megadose vitamins A, B6, C and E plus zinc decrease bladder tumor recurrence in patients receiving BCG immunotherapy. Further research will be required to identify which ingredient(s) provide this protection.

Edes T.E.; Gysbers D.S.; Packer L.; Bertram J.; Heimburger D.; Krinsky N.
University of Missouri, Columbia, 800 Hospital Drive, Columbia, MO 65201 USA
Ann. New York Acad. Sci. (USA), 1993, 686/- (203-212)

Exposure to benzopyrene, an enzyme-inducing PAH carcinogen, promotes vitamin A depletion in exposed tissues. This effect is evident while on a vitamin A sufficient diet and without a decline in serum retinol. The finding of local tissue vitamin depletion without systemic depletion may have considerable implications in maintaining tissue health. While the described studies involved dietary exposure to benzopyrene, it is reasonable to extrapolate that inhalation exposure via cigarette smoke would have a similar effect in the lungs and perhaps stomach and bladder. Higher MFO enzyme activity in the lungs may have detrimental effects. Kellermann's early work identifying a higher incidence of lung cancer in those with genetically greater aryl hydrocarbon hydroxylase activity was interpreted as due to the greater formation of a reactive intermediate in the process of carcinogen metabolism. As an alternative hypothesis I suggest that those with higher enzyme inducibility may have greater carcinogen-induced vitamin A depletion. If poor tissue vitamin A nutriture potentiates the carcinogenicity of compounds such as benzopyrene, dietary or pharmacologic interventions which improve tissue nutriture could be important. The demonstrated effect of dietary beta-carotene on preventing carcinogen-induced tissue vitamin A depletion suggests one mechanism by which beta-carotene may be cancer protective. Further investigations are warranted, particularly with inhalation exposure to carcinogens and the effect of dietary beta-carotene on lung tissue nutriture.

Paganini-Hill A.; Chao A.; Ross R.K.; Henderson B.E.
Department of Preventive Medicine, University of Southern California School of Medicine, Los Angeles, CA 90033-0800 USA
J. Natl. Cancer Inst. (USA), 1987, 79/3 (443-448)

A cohort of 10,473 residents of Leisure World, Laguna Hills, CA, who were initially free of cancer were followed from 1981 to 1986. A health survey questionnaire completed by all cohort members included usual frequencies of consumption of certain food items, including vegetables, fruits, dairy products, liver, and cereal, as well as specific information on brand and formulation of vitamin supplements containing vitamins A, C, or E. Pathologic diagnosis of incident cancer was confirmed in 643 persons (56 lung, 110 colon, 59 bladder, 93 prostate, 123 female breast, and 202 cancers of other sites). Our study found little indication that increased intake of vitamin A or beta-carotene from the diet or supplements protects against the development of cancer overall. Dietary vitamin A intake was highly associated with smoking status; 25% of current smokers were in the highest third of dietary vitamin A consumption versus 32% of past smokers and 36% of never-smokers. In males who never smoked there was some indication that cancer rates decreased with increasing vitamin A intake, but the results were not statistically significant.

Clerici M.; Pastorino U.; Labianca R.; et al.
Ospedale S. Carlo Borromeo, Divisione di Oncologia Medica, Milano Italy
Minerva Med. (Italy), 1987, 78/6 (377-386)

The role of vitamins A, E, C, D, folates and selenium in the chemical prevention of tumours and/or precancerous conditions is examined in the light of epidemiological studies and experimental observations. Particular mention is made of significant clinical studies that provide valuable indications about the use of vitamin A and its derivatives, in particular for the treatment of precancerous and cancerous conditions. Vitamin A and its derivatives apparently play a fundamental role not only in the treatment of proliferating malignancies of the skin (carcinomas, severe actinic keratosis) or involving the skin (fungoid mycosis, skin metastases of solid tumours) but also in the prevention of recurring bladder tumours and the treatment of several bronchial dysplasias.

Nomura A.M.Y.; Stemmermann G.N.; Heilbrun L.K.; et al.
Japan-Hawaii Cancer Study, Honolulu, HI 96817 USA
Cancer Res. (USA), 1985, 45/5 (2369-2372)

Serum specimens were obtained from over 6800 men of Japanese ancestry in Hawaii from 1971 to 1975. Since then, the following numbers of newly diagnosed cancer cases have been identified: 81 colon, 74 lung, 70 stomach, 32 rectum, and 27 urinary bladder. The stored sera of the cases and 302 controls were tested to determine their beta-carotene, vitamin A, and vitamin E levels. There was no association of either vitamin A or E with any of the cancers. For serum beta-carotene, there was a significant association only with lung cancer (20.0 mug/dl in cases versus 29.0 in controls, P < 0.005). The lung cancer odds ratio for men in the lowest quintile of beta-carotene was 3.4 relative to men in the highest quintile. These findings suggest that a low serum beta-carotene level is a predictor of increased lung cancer risk in men.

Mahmoud L.A.N.; Robinson W.A.
Dep. Clin. Pathol., Fac. Med., Mansoura Univ., Mansoura Egypt
Int. J. Cancer (Switzerland), 1982, 30/2 (143-145)

The following studies were undertaken to determine the levels of serum carotene and vitamin A (retinol) in Egyptian patients with intestinal, urinary, hepatosplenic schistosomiasis, and bladder cancer. These studies have shown that both serum carotene and serum retinol levels are significantly reduced in patients with bladder cancer when compared to controls. These data, when viewed in light of previous animal studies noted, raise the question as to whether vitamin A administration can be beneficial in the prevention and/or treatment of human bladder cancer, particularly that associated with schistosomiasis.

Basu T.K.; Rowlands L.; Jones L.; Kohn J.
Dep. Biochem., Univ. Surrey, Guildford United Kingdom
Eur. J. Cancer Clin. Oncol. (England), 1982, 18/4 (339-342)

Serum vitamin A and retinol-binding protein (RBP) concentrations were measured in patients comprising 53 myeloma and 28 epithelial cell cancer cases. Vitamin A levels in these patients were found to be significantly lower than those in the 30 healthy subjects, the effect being more marked in the patients with cancer of epithelial origin. The serum concentrations of retinol-binding protein (RBP) fell in parallel with vitamin A in the epithelial cancer patients, while the RBP concentrations remained unaffected in the patients with myeloma, suggesting that the underlying factor for resulting low vitamin A levels may be different in these two groups of patients.

El-Aaser A.A.; El-Merzabani M.M.; Abdel-Reheem K.A.; Hamza B.M.
Dept. Cancer Biol., Nat. Cancer Inst., Cairo Egypt
Tumori (Italy), 1982, 68/1 (19-22)

The possible role of vitamin A in the pathogenesis of bilharzial bladder cancer among Egyptians, particularly as it relates to the histopathologic tumor type, was investigated. Bilharzial patients and bladder cancer patients with squamous cell carcinoma, the most prevalent type in Egypt, showed significantly lower levels of vitamin A than normal male subjects. In contrast, bladder cancer patients with transitional cell carcinoma had levels that were not significantly different from normal male subjects. The possible role of vitamin A in the etiology of bilharzial bladder cancer is discussed.

Mettlin C.; Graham S.; Priore R.; et al.
Roswell Park Mem. Inst., Buffalo, NY USA
Nutr. Cancer (USA), 1981, 2/3 (143-147)

The reported dietary, alcohol consumption and smoking habits of 147 Roswell Park Memorial Institute white male patients diagnosed with cancer of the esophagus were compared with the reports of 264 white males of comparable ages with diagnoses other than cancer. Overall frequency of vegetable and fruit consumption was associated with lower risk; persons reporting fruit and/or vegetable consumption 31-40 times a month had significantly greater risk than those who reported consumption 81 times a month or more. Calculated indexes of vitamin A and vitamin C intake were similarly related to reduction in risk. Dose-response gradients were observed for frequency of vegetable and/or fruit consumption, as well as for vitamin A and C intake. The putative protective effect of vegetable and fruit intake remained evident after controlling for its possible association with smoking and drinking. Previously reported associations of smoking, alcohol use and social class, as measured by type of occupation, were replicated in these data. The findings of this investigation are consistent with evidence of lower risk associated with vegetable consumption in instances of colon, lung, bladder, oral, and laryngeal cancers, and with evidence of tumor inhibition by vegetable proporties in animals. Interpretation of the findings is limited by the difficulties of retrospective assessment of dietary intake and by possible confounding by other factors known to be related to esophageal cancer.

Stammwitz U.
U. Stammwitz, Schape and Brummer GmbH and Co. KG, Bahnhofstrasse 35, 38259 Salzgitter-Ringelheim Germany
Zeitschrift fur Phytotherapie (Germany), 1998, 19/2 (90-95)

For herbal urinary antiseptics a positive monograph by the commission E of the former German Bundesgesundheitsamt (BGA) has been issued for bearberry leaf horseradish roots and white sandalwood. Bearberry leaf is the only one of these drugs suited for the (sole) therapy of inflammable diseases of the lower urinary tract. Recent investigations regarding pharmacokinetics and toxicology of Uvae-ursi folium confirm the precautionary nature of restricting the application. Herbal urinary antiseptics are preferred if antibiotic treatment/chemotherapy is not considered essential: for uncomplicated cystitis, asymptomatic bacteriuria or in patients with permanent catheter.

Yu Y; Hu J; Wang PP; Zou Y; Qi Y; Zhao P; Xe R
Harbin Engineering University, China.
Eur J Cancer Prev (England) Aug 1997, 6 (4) p363-9

A case-control study of risk factors for bladder cancer was carried out in Heilongjing Province, China. Between May 1989 and May 1990, 217 histologically confirmed cases of bladder cancer and 254 controls with non-neoplastic and non-urine system disease were recruited. Individuals were interviewed in the wards of six major hospitals. Controls were matched by sex, age and area of residence. Information was collected concerning economic status, occupation, histories of smoking and consumption of alcohol, use of tea, the taking of analgesics, dietary histories and previous diseases. Odds ratios (ORs) were calculated from stratified analysis and conditional logistic regression models. Increased risk was observed with increasing times per year and number of years of saccharine use. Compared with non-users, the use of saccharine for more than 19 times per year, and for more than 15 years, the adjusted ORs were 3.9 (95% CI = 1.8-8.67) and 5.1 (95% CI = 2.3-11.6), respectively. Statistically significant associations were also found for diseases related to the urinary system (OR = 2.8; 95% CI = 1.1-7.6). Increased consumption of fruit and vegetable may reduce the risk of bladder cancer. Cigarette smoking had no effect on the risk of bladder cancer in both genders. There was no association between the consumption of alcohol or tea, or types of water supply, with bladder cancer risk.

Hoskin PJ; Saunders MI; Phillips H; Cladd H; Powell ME; Goodchild K; Stratford MR; Rojas A
CRC Tumour Biology and Radiation Research Group, Mount Vernon Hospital, Middlesex, UK.
Br J Cancer (Scotland) 1997, 76 (2) p260-3

Carbogen and nicotinamide have been evaluated in a phase II study as hypoxia-modifying agents during radical radiotherapy for bladder cancer using a standard daily 20-fraction schedule. Three groups of patients have received (a) nicotinamide alone, given orally in a dose of 80 mg kg(-1) daily with 52.5 Gy in 20 fractions over 4 weeks, (b) carbogen alone, with 50 Gy in 20 fractions over 4 weeks, and (c) carbogen and nicotinamide, with 50-52.5 Gy in 20 fractions over 4 weeks. Ten patients were treated in each group. All patients completed carbogen and radiotherapy as prescribed, but only 45% completed daily nicotinamide over the 4-week treatment period. The end points of this study were acute bowel and bladder morbidity and local control at cystoscopy 6 months after treatment. An expected level of acute bowel and bladder morbidity was seen that reverted to normal in most patients by 12 weeks with no difference between the three treatment groups. Complete response rates at 6 months were seven out of ten (100%) in the nicotinamide alone group, nine out of ten (90%) in the carbogen alone group and seven out of ten (70%) in the carbogen and nicotinamide group. It is concluded that carbogen and nicotinamide may improve the results of daily fractionated radiotherapy in bladder cancer and that further evaluation is required.