The workplace as a cause of cancer--part II.
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Biomedical subjects
Publications and source records attributed to D Schottenfeld.
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The Memorial Hospital, New York, surveys of multiple primary cancer risks undertaken during 1965-1971 are summarized. After re-examination the methodological problems noted were: 1) that prospective studies tell us more than prevalence or retrospective studies; 2) that risks must be related to the observation period, patient's ages, etc.; 3) that hospital series probably are selected but that this may be overcome by internal comparisons; 4) that the search for explanatory variables is difficult, to the extent data on these variables were not explicitly collected; and 5) that computing multiple risk ratios for each of many cancer types guarantees a number of accidentally statistically significant results. It was also concluded that most cancer patients have excess risk for specific later cancers, depending on their original cancer type and that knowledge of these risks is of true clinical importance.
Forty-four antecedent, synchronous, and metachronous multiple primary cancers were identified among 41 patients who constituted 4.0% of 1028 patients initially treated for Hodgkin's disease during the years 1950-1954, 1960-1964, and 1968-1972. At 5 years post-therapy the cumulative probabilities of developing a multiple primary cancer for patients treated in 1950-1954, 1960-1964, and 1968-1972, were 1.14%, 1.48%, and 4.43%, respectively. At 10 years the cumulative probability of a multiple primary cancer was 2.54% for the 1950-1954 treatment group and 6.52% for the 1960-1964 treatment group. Among those patients 16-39 years of age, initially treated during the period 1960-1964, who had survived 6-10 years after receiving radiation plus single agent chemotherapy, we observed a significant 18-fold increase in the number of multiple primary cancers. A significant occurrence of two multiple primary cancers in a relatively small group of patients treated with chemotherapy only during the period 1968-1972 was also noted. Continued surveillance of patients extensively treated with combination chemotherapy and radiotherapy will enable assessment of the oncogenic potential of these modern therapeutic approaches to the management of Hodgkin's disease.
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A screening program for colorectal cancer and adenomas has been applied to 6,579 mostly asymptomatic men and women age 40 years and older utilizing fecal occult-blood testing followed by investigation of patients with positive slides by air-contrast barium enema and colonoscopy. A control population of 7,325 patients had sigmoidoscopy only and no occult-blood testing. Approximately 1% of the patients had positive slides; most patients had only one or two slides positive. Approximately 50% of patients with positive slides had significant neoplastic lesions, including 23 patients with large adenomas and 7 patients with cancers. Pathological staging of cancers was more favorable in the screened asymptomatic group as compared with the control group. Neoplastic lesions seen on sigmoidoscopy in screened patients who had negative fecal occult-blood tests included 2 cancers and 15 large adenomas. Reasons for false negativity include possible conversion of initially positive slides to negative. Screening for colorectal cancer and adenomas with fecal occult-blood testing appears to be feasible approach with good patient compliance, and manageable rate of positive slides productive of a high percentage of neoplastic lesions. The number of false-positives seems to be low. False negativity has been observed and will require further study.
During the years 1954 through 1964, 259 individuals with primary malignant melanoma had an elective node dissection. Microscopic metastases were found in 15% of these patients. The presence of only a microscopic focus of involvement gave a 10-year cure rate of 67%; metastasis larger than a microscopic focus in a single node, 50%; and more than one node, 15%. One hundred forty-five individuals were treated by wide excision alone with 18% subsequently requiring a therapeutic lymphadenectomy with a ten-year cure of only 6%. A prospective study was then initiated which was concerned with efficacy of selection of patients for elective node dissection. Clark's level of invasion was determined for 258 patients treated since January 1972. The depth of invasion of the primary lesion was found to correlate directly with the absence of lymph node metastases, extent of nodal involvement, and rate of recurrence. It is concluded that the concept of elective node dissection is valid.
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The influence of pregnancy on the prognosis of cutaneous melanoma in women of childbearing age was examined in a retrospective review of 251 surgically treated cases. There was no statistical difference in survival at five years, free of disease, for Stage I melanoma between nulliparous, parous nonpregnant, and pregnant women. For Stage II melanoma, however, a significantly lower survival rate was observed for pregnant patients (29%) and parous women who had experienced activation of the lesion in a previous pregnancy (22%), as compared with that of nulliparous patients (55%) and other patients in the parous group (51%); p less than 0.05. This discrepancy in survival, together with the observed higher frequencies of Stage II cases, melanomas occurring on the trunk, and symptoms such as bleeding, ulceration, irritation, and elevation of the lesion, strongly suggest an adverse influence of pregnancy on women with Stage II melanoma.
After all records of patients with breast cancer who received primary treatment at Memorial Hospital in 1960 were reviewed, 304 women with operable, infiltrating carcinoma were identified and classified clinically according to the TNM system of the American Joint Committee for Cancer Staging and End Results Reporting. There were 66 patients (22%) classified under Stage I, 176 (58%) under Stage II, and 62 (20%) under Stage III. There were 82 patients (27%) in whom the nodal status was misclassified clinically. The observed 10-year survival was 59.7%. The 10-year end results (with 95% confidence limits) diminished significantly in relation to advancing clinical stage of disease--90.9% (+/-6.9%) for Stage I, 57.1% (+/-7.3%) for Stage II, and 33.9% (+/-11.8%) for Stage III patients. The 10-year survival in patients with pathologically negative axillary nodes was 71.5%, and in the patients with pathologically positive axillary nodes, 48.3%.
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En bloc resection of the primary melanoma with the regional lymph node drainage basin as a method of controlling disease within the area was used in 281 patients with stage I or II melanoma arising on the extremities (proximal to wrist or ankle) or on the trunk from 1954 through 1964. The en bloc operation was performed in 212 patients with a five-year cure of 73.5% (156 of 212). Seventy-six percent had histologically negative nodes. Only 2% developed regional recurrence. Sixty-nine patients had a discontinuous dissection. The five-year cure was comparable: 68% (47 of 69). The incidence of histologically negative nodes was similar (77%), but the regional recurrence rate was 14%. This difference is significant at P < .01. The incontinuity or en bloc procedure appears highly effective for its designed purpose.
With increasing evidence that cancer patients respond immunologically to their cancers, it seemed interesting to investigate whether or not the course of the second cancer differed from that of the first. If we assume that, in analogy to mammary cancer in the mouse, the cells of human breast cancers carry shared antigens (although this is by no means certain), we could expect that sensitization of the patient induced by the first cancer would enhance his immune response to the second and that this might be reflected in an altered clinical course. We evaluated 82 patients with a second breast cancer and found no difference in the course of the second cancer as compared with the first.
Treatment of mammary carcinoma by partial mastectomy rather than by total mastectomy and axillary dissection may diminish the chances of long-term cure by risking incomplete removal of all local carcinoma at the initial operation. This study was undertaken to determine by pathologic examination how often carcinoma might remain in the breast and axilla after partial mastectomy. The operation was simulated in 203 mastectomy specimens after operations for unilateral invasive carcinoma. In so far as could be determined on gross examination, the entire primary lesion was included in the quadrant which was excised in the simulated procedure. Among 100 women with primary lesions less than 2 cm in diameter, 26% had carcinoma in the breast which remained after simulated partial mastectomy. Six percent of them also had axillary node metastases. An additional 30% only had axillary node metastases. When the primary lesion was more than 2 cm in diameter, 38% of patients had carcinoma in the breast after simulated partial mastectomy, of whom 29% also had axillary metastases. After simulated partial mastectomy, carcinoma was found in 80% of breasts from patients with lesions in the subareolar area, in contrast with 25-35% of patients with a primary carcinoma in one of the four quadrants. None of the 9 patients with medullary and colloid carcinomas that measured under 2 cm had axillary metastases or carcinoma in the breast outside of the primary quadrant. The findings suggested that a familial history of breast carcinoma or a large primary lesion may be associated more often with multifocal disease, but factors such as age at diagnosis, axillary status, and the mammogram report did not have significant predictive value for distinguishing between patients who did or did not have carcinoma in breast tissue after the primary had been removed by a simulated partial mastectomy.
An unusual cluster of 11 patients with Pneumocystis carinii pneumonia occurred in a 3-month period at Memorial Hospital, New York. Ten of the 11 patients had lymphoma or leukemia. In 7 patients, corticosteroid therapy was decreased or stopped shortly before pneumocystis pneumonia was diagnosed. The pediatric patients had extensive contact in the outpatient department, and three of them had roomed together, suggesting the possibility of man to man transmission. Tree of 4 adult patients with Hodgkin's disease and pneumocystis pneumonia had the same physician. This physician had an indirect immunofluorescent titer of 1:16, as did an infectious disease resident involved in the care of 6 patients. Three of 9 patients tested showed indirect immunofluorescent titers of 1:16 or above, with rising or falling titers on serial specimens. Although definitive evidence of communicability was not established, patients with suspected or proved pneumocystis pneumonia are now isolated in this hospital.