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Tuu, 0ou.NLcir, For Z`om~,cco P.E SEacrz' New F,nglar.d Deaconess or New England Baptist Hospitals, but recently we have begun 3. The pathology ar.d clinical course of patients with bladder cancer. 0 CTR GRANT N0. 558' G. H. FRIEIDELL, M.D. Cancer Research Institute New England Deaconess Hospital 194 Pilgrim Road Boston, Massachusetts 02215 PROGRESS REPORT NO. 1 November'l, 1966 - June 30, 1967 THE PATHOGLNL'SIS OF HUt4A.N BLADDER CANCER The specific aims of this project were to study the relationship between: 1. Detailed smoking, occupational, residential and family histories; 2. Levels of urinary excretion of urinary metabolites; and I will briefly discuss our procgress with regard to each of these specific afms. Interview Studies We have interviewed141 patients with~bladder cancer, 106 males and 35 females. A majority of interviews were patients originally treated at either the to inte.rvicw patients treated in the Boston Veteran's Administration Hospital as Q. - O.. Well. We are pleased at gaining access to this latter group of patients for we CJ feel it represents a different population than we had previously been studying. For example, in 4 of the first 16 cases seen at the V. A. Hospital a history of employment in the rubber industry was found. We have interviewed 176 control subjects, 90 male and 86 female. The selection of an appropriate control population for such an interview study has been soMewhat difficult, however, and we have enlisted the assistance of epidemiologists at the Harvard~School of Public Health in making this selection. They have beemof oxeat help to us, but in addition, and perhaps of greater sionific2.nce, I believe members of that department have become sufficiently interested in exploring the epidemiology of

bladder cancer to collaborate in a more extensive interview study. This study • would cover the greater Boston area and should more accurately reflect the pos- sible influence of environmental factors in the pathogenesis of this disease. Thus far 340 of the females and 75°,; of the male bl.tdder cancer patients in our control population, but at present we are attaching no significance to tnese ,~ who have been interviewed have smoked. This is approximately the same ratio as figures. No significant trend is yet apparent in our data concerning occupational or residential history but 48% of the female and 430 of the male population with bladder cancer have a family history of cancer. Again I am reluctant to comment about the sionificance of these numbers until we have reviewed our data with our statistical consultants. Council For Tobacco Research-USA we had obtained the part-time services of Dr. Carl Cornil, a trained~ urologist. of a second trained interviewer and with the additional funds furnished by Th By the end of the period covered in this report we had obtained the services Tryptophan Metabolites With regard to tryptophan metabolite excretion we have carried out 24, 4~C or 96 hour studies on 63 patients and 32 controls. t;ot all of the urine samples have been 0 assayed but thus far it would appear that approximately one third of the patients with bladder tumors have abnormal excretion of tryptophan n,etabolites. If one excludes patients with papillomas from the group of tu~aor cases, approximately one half of the remaining patients have abnormal values. This latter figure is similar to the one originally published by Price and his co-workers for the 41 Madison patients with bladder tu^ ors . 100354s i 24 In~our material it would appear that the histolo.-ical grade and extent of the tumors are related to abnormal urinary metabolite concentrations. A review of the original patholo3ical material from Dr. Price's group of 41 cases suggests that in

this group also the extent of the tumor was related~ to the presence or absence of abnormal urinary metabolite values. This review was conducted by Dr. Safouh Atassi and me in Madison within the past few months. Pathology and Clinical Course Dr. Spencer Burney and I, in Boston, have almost completed our review of the patholo~y from all of the bladder tumor patients whom we have thus far interviewed. ving their primary therapy will be found in the first 5 years after treatment. We will shortly have fairly complete information about 5, 10 and 15 year survival in Hospitals. From this review the fact has emerged that the majority of patients survi- patients treated for bladder cancer at the New E'ngland Deaconess and~ A*ew Enoland Baptist A great deal of time and energy has been spent following up the histories of all within the next few months. sections were prepared. These latter studies should be suitable for publication In~addition we are almost through with a review of 25 cases in which giant histologic • bladder cancer patients treated at these two institutions. Such information has heretofore not been available. Financial Support U. S. Public Health Service to continue our bladder cancer studies for a 4 year period. Finally, it should be noted~that we have been awarded a researchigrant from the This grant will supplement funas from The Council For Tobacco Research-USA for the first 2 years and then will furnish entire support for the last 2 years of our pro:osed research project. The grant year for the ?ublic Health Service award began April 1, 1967. The sums awarded for each of the 4 grant years are $31, 307 . 00, $45, 935 . C0, ~.a $57,185.00, and $13,701.00. • C 0 GJ UZ At this time we hope that The Council For Tobacco Research-USA will see fit to renew its aNard to us for a second year beginning November 1, this project beyotid the second grant year. 1967. We do not anticipate asking The Council for additional support for CA