Gilbert H. Friedell

Occupation and cancer of the lower urinary tract.

Lifetime occupation histories were elicited from 461 persons with transitional or squamous‐cell carcinoma of the lower urinary tract, 94% of whom had a bladder tumor. This was a sample of all such persons newly diagnosed in a designated area in eastern Massachusetts during a recent 18‐month period. A sample of 485 persons from the population of the entire study area provided comparable histories and serves as a control group. Occupations were classified according to two schemes developed for this study. Among men, excess risk of lower urinary tract cancer was found in 5 of 8 occupation categories where this was suspected a priori: dyestuffs, rubber, leather and leather products, and paint and organic chemicals. Although suspected, excess risk was not confirmed for 3 categories: printing, petroleum, and chemicals other than organic. The relative risks for men ever employed in the rubber industry (1.63) and in the leather industry (2.25) are statistically significant, p < 0.05. In absolute terms, the 5 risk categories account annually for 7.3 cases of lower urinary tract cancer per 100,000 men aged 20–89; this is about 18% of male bladder cancer. Among women, the comparable figures are 0.8 cases and 6% of the disease. None of the associations of bladder cancer with occupation results from any indirect association with cigarette smoking. Although requiring cautious interpretation, the data suggest increased risk in 2 occupation groups not previously suspected: cooks and kitchen workers and clerical workers.

Treated History of Noninvasive Grade 1 Transitional Cell Carcinoma

A total of 178 patients with grade 1 noninvasive (stage Ta) bladder tumors followed from 1 to 10 years (median 58 months) was prospectively evaluated by cystoscopy, transurethral resection, mucosal biopsies, cytology, size and number of tumors at diagnosis, recurrences, progression in grade and stage, number of negative or positive cystoscopies and death from all causes. Histopathological and cytological studies were confirmed by a Central Pathology Laboratory using the criteria for grade 1 as described previously. Of the patients 122 (68.5%) had a single tumor. Three-quarters of the patients had tumors of less than 2 cm., 95% had mild or no urothelial dysplasia and 1 had positive cytology results. There were 419 recurrent tumors in 109 patients (61%). Patients with multiple tumors were at a significantly greater risk for recurrences (p < 0.001). Size of tumor significantly affected the rate of recurrence in the first 2 years after initial diagnosis in single tumor patients only. Of the multiple tumor patients 90% experienced a recurrence compared to 46% of the single tumor patients. Of the 1,112 cystoscopies performed in 122 single tumor patients 18% were positive, compared to 33% of the 686 cystoscopies performed in 56 multiple tumor patients. A total of 29 patients had a change in grade, 5 having grade 3 and 24 having grade 2 tumors. Progression to stage T1 occurred in 5 patients and to stage T2 or greater in 3. Of the 36 patients who died, 1 died of obstruction due to bladder cancer. Experimental evidence supports the opinion that the cells of stage Ta, grade 1 tumors are different in several ways from normal urothelium. There are little data to support the use of the term papilloma to describe stage Ta, grade 1 tumors without reservation. The data demonstrate that the tumor diathesis being expressed ceases with time and for unknown reasons. Multiple tumor patients with stage Ta, grade 1 disease might be included in chemotherapy trials only with stratification and a control arm of transurethral resection/fulguration alone.

Long-term Fate of 90 Patients with Superficial Bladder Cancer Randomly Assigned to Receive or not to Receive Thiotepa

We assigned randomly 90 patients treated previously for superficial transitional cell carcinoma to conventional followup or prophylactic treatment. This followup study details the late incidence of recurrence (29 of 45 patients in the prophylactic group and 34 of 45 controls), the progression of tumor grade and stage, the deaths and causes (24 patients), and the influence of initial stage, grade, carcinoma in situ and positive cytology on the outcome of treatment.

Prognostic factors in cancer of the female breast. II. Reproducibility of histopathologic classification

The reproducibility of histopathologic classification of breast tumor tissue (nuclear grade) and of axillary lymph nodes (sinus histiocytosis) has been evaluated. In 2 independent readings, an experienced observer assigned 70% of tumor tissue slides and 70% of lymph node slides to the same classification. Two other pathologists agreed fairly well with the classification by the experienced observer. Nuclear grade and sinus histiocytosis were found to be related to patient survival on the basis of classification by each of the 3 pathologists.

„NORMAL” urothelium in patients with bladder cancer. A preliminary report from the national bladder cancer collaborative group a

The concept that most bladder carcinomas arise from a widespread reaction of urothelial cells to various carcinogenic stimuli is widely accepted. The evidence for this theory rests largely on retrospective evaluations of nontumorous urothelium obtained from patients with concomitant or sinecomitant bladder cancers. A prospective surveillance study of patients with bladder cancer has been conducted at the University of Tennessee Center for the Health Sciences, a collaborating institution of the National Bladder Cancer Collaborative Group‐A, to determine the frequency, distribution, and biologic significance of hyperplasia, dysplasia, carcinoma in situ (CIS), and carcinoma in the cystoscopically unremarkable urothelium of patients with carcinoma of the bladder.

The pathology of human bladder cancer.

The pathologist plays a key role in the detection and diagnosis of bladder cancer, as well as in the development of strategies for the clinical management of this disease by the urologist. In order to make appropriate decisions, the urologist needs help from the pathologist in determining: 1) whether or not a bladder tumor is present; 2) if present, its histologic type, grade, depth of invasion and evidence of lymphatic or blood vessel invasion; 3) whether or not there are associated neoplastic lesions elsewhere in the bladder —or elsewhere in the lower urinary tract; and 4) if some therapeutic modality has been directed toward the neoplastic tissue, the completeness of tumor removal or destruction. It is recommended that the WHO classification of bladder tumors be used by pathologists in their reports to facilitate communication among pathologists, urologists, radiation therapists, medical oncologists, and others involved in the management of bladder cancer patients. In addition, the pathologist should make a definite statement regarding the presence or absence of muscle tissue in every bladder biopsy specimen containing tumor. After one or more superficial tumors are identified by the urologist and treated by transurethral means, management of the patient will depend not only on the microscopic evaluation of the resected tumor but also on an accurate assessment of the neoplastic potential of the remaining epithelium. The cytopathologic examination of urine samples or bladder washings aids this assessment.

Are the known bladder cancer risk-factors associated with more advanced bladder cancer?

Risk factors for superficial and invasive bladder cancer were examined in a case-control study of 470 cases Identified in 1967–68 in the Brockton and Boston Standard Metropolitan Areas (MA, United States) and of 500 population-based controls. Histologic specimens were reviewed and classified as superficial or invasive, following a standardized protocol. The tobacco-associated risk for superficial bladder cancer was odds ratio (OR)=2.6 (95 percent confidence interval [CI]=1.7–4.1) and the risk for invasive bladder cancer was OR=1.7 (CI=1.1–2.5). For subjects less than 60 years of age, the risks were greater for invasive tumors (OR=4.3, CI=1.2–15) than for superficial tumors (OR=0, CI=0.9–4.2), but this pattern for tobacco use was not found in older subjects. A strong trend of increased risk with increased amount of cigarettes smoked was shown only for invasive bladder tumors. No clear pattern of excess risk for invasive bladder tumors was seen for age at first use and years since last use of tobacco. The risk associated with occupational exposure to aromatic amine bladder carcinogens was OR=1.7 (CI=0.8–3.3) for superficial and OR=1.5 (CI=0.8–3.0) for invasive bladder cancer. For subjects less than 60 years of age, the risks were greater for invasive (OR=12.0, CI=2.1–65) than for superficial tumors (OR=4.3, CI=0.8–24), but this pattern for occupational exposure was not found in older subjects. Risk by age at first exposure to occupational aromaticamine, bladder carcinogens was similar for superficial and invasive tumors. Overall, there was no association between known bladder-cancer risk-factors and more advanced bladder cancer. The relative risk associated with cigarette smoking and occupational exposure to aromatic amines was higher for invasive than superficial cancer only for men less than 60 years of age.

Raynaud's Disease and Primary Pulmonary Hypertension

A case of Raynauds disease with autopsy is reported in which the clinical picture was dominated by pulmonary hypertension apparently unassociated with any significant pulmonary parenchymal disease. Microscopically cellular intimal proliferation of small pulmonary muscular arteries and arterioles was the most characteristic lesion. In several proximal medium-sized muscular arteries there was necrotizing arteritis with thrombus formation. Similar vascular lesions were not found in other organs, although generalized arteriosclerosis and arteriolosclerosis were present. The pulmonary vascular changes are thought to represent a local exacerbation of generalized vascular disease, but a specific etiology was not apparent.

Multiple Malignancies in the Urinary Bladder Following a By-pass Procedure

A case with two separate transitional cell carcinomas of the bladder is reported in which neither tumor was evident on cystoscopy six months prior to resection. Transplantation of the ureters into an ileal loop, performed for chronic cystitis of long duration, did not prevent development of the tumors. Extensive atypical epithelial hyperplasia and areas of carcinoma in situ were noted in the giant tissue sections prepared from the cystectomy specimen. These changes were not evident in biopsy specimens taken from the bladder six months before the cystectomy, although a segment of distal ureter had had atypical epithelial hyperplasia five months before tumor was clinically evident in the bladder.

Tryptophan Metabolism in Patients with Bladder Cancer of Occupational Etiology

Excretion of urinary tryptophan metabolites after a 2-gm load of L-tryptophan was measured in patients with occupational bladder cancer (due to exposure to aromatic aimines), and in matched exposed and unexposed control subjects from the same factory. No significant differences were found in mean excretions of kynurenine, acetylkynurenine, hydroxykynurenine, kynurenic acid, xanthurenic acid, indican, anthranilic acid glucuronide, o-aminohippuric acid, or creatinine. Some individual subjects had slight elevations of metabolites so that 2 of 8 patients with bladder cancer present, and 2 of 10 with a diagnosis of bladder cancer but free of disease when studied, were classified as having abnormal tryptophan metabolism. In this regard, their tryptophan metabolism resembled that of male patients from Boston (15% abnormal) rather than that of male patients from Wisconsin (35% abnormal).