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R A Kleinerman

Publications and source records attributed to R A Kleinerman.

49 records · Page 3Linked to original sources

Second cancer following cancer of the female genital system in Connecticut, 1935-82.

The risk of second primary cancer was evaluated in more than 25,000 women with cancer of the genital organs diagnosed between 1935 and 1982 in Connecticut. Significant excesses of subsequent cancers were observed following cancers of the cervix (35%, n = 656), uterine corpus (16%, n = 1,060), and ovary (58%, n = 366). When observed and expected second cancers of the female genital tract were excluded, these excesses became 40%, 30%, and 59% after cervix, uterine corpus, and ovary, respectively. Among women with either cancer of the cervix or uterine corpus, the risk of developing a second cancer rose with increasing duration of follow-up, reaching an excess of 61 and 34%, respectively, after 20 years. In contrast, among patients with ovarian cancer, the second cancer risk decreased over time to 41% after 10 years. Cancers related to smoking, i.e., oral cavity and pharynx, esophagus, and respiratory system, were notably increased among cervical cancer patients. The twofold to threefold risks observed for these second cancers are consistent with recent evidence linking cervical cancer to cigarette smoking and seem too large to be artifacts of confounding by low socioeconomic status. An increased incidence of second cancer of the abdominal organs (colon, rectum, kidney, bladder, ovaries) was generally observed for each gynecologic site. However, only rectal cancer was consistently linked with radiation treatment for the first primary cancer. Leukemia occurred in excess after cancers of the uterine corpus and ovary, but not after cervical cancer. The predominant cell type was acute nonlymphocytic leukemia, and the excess was associated with radiotherapy for uterine corpus cancer and with chemotherapy for ovarian cancer. Cancers of the breast and colon were increased following uterine corpus and ovarian cancer and vice versa, which supports the notion that these sites share a common etiology, perhaps related to dietary or hormonal factors. Cervical cancer patients experienced a deficit of subsequent breast cancer, possibly due to ovarian removal or ablation by radiation. Investigators need to explore further the association between the smoking-related cancer sites and cervical cancer, to clarify the role of radiotherapy and chemotherapy in relation to excess cancers, and to define more fully the etiologic factors that link cancers of the breast, colon, uterine corpus, and ovary.

Breast Neoplasms↗

Cancer registration in Connecticut and the study of multiple primary cancers, 1935-82.

The Connecticut Tumor Registry (CTR) was established in 1941 and is the oldest population-based cancer registry in the world. Since 1935, all malignant tumors have been registered, and cancer patients are followed annually for vital status. Reporting by hospitals of all cancers diagnosed in Connecticut residents became mandatory in 1971. The reporting physician or hospital makes the initial determination as to whether a tumor is an independent primary cancer, recurrent tumor, or metastatic lesion. In addition, the Registry maintains stringent quality control procedures to avoid duplication of cancer reports. The Registry reviews reports of new cancers developing in patients with a previous primary cancer to rule out the possibility of misdiagnosed metastases. Microscopic confirmation of the diagnosis has improved from 49% in 1935-39 to 94% in 1980-82. Cancers reported only from death certificates currently account for only 1% of all registrations. Between 1935 and 1979, cancer rates in Connecticut almost doubled among males and increased by more than one-third among females; notable increases were seen for cancers of the lung and prostate in males and cancers of the lung and breast in females. In recent years, rates for malignant melanoma of the skin have increased dramatically among both sexes. Stomach cancer has decreased over time in both sexes, as has cervical cancer in females. Although the CTR has used several revisions of the International Classification of Diseases to code the primary site of cancers, rules for the coding of multiple primary cancers have remained essentially the same. Among 253,536 individuals diagnosed between 1935 and 1982 with an invasive cancer, 16,727 (6.6%) nonsimultaneous second cancers were evaluated and are discussed in subsequent chapters of this monograph. Simultaneous cancers were diagnosed in 4,107 individuals and accounted for approximately 20% of all multiple cancers reported in Connecticut. The most frequent simultaneous tumors were cancers of the colon, rectum, prostate, lung, breast, and bladder. Some simultaneous cancers (chronic lymphocytic leukemia, testis, prostate, rectum, uterine corpus, and liver and biliary tract) occurred almost as frequently as the number of subsequent nonsimultaneous tumors, which suggests that the patterns of risk over time for certain sites may be distorted when diagnoses are advanced in time and removed from analysis.(ABSTRACT TRUNCATED AT 400 WORDS)

Age Factors↗

Second cancer following cancer of the male genital system in Connecticut, 1935-82.

The risk of a second primary cancer developing was evaluated in nearly 20,000 men with cancers of the prostate or testis in Connecticut, 1935-82. Among 18,135 men with prostate cancer, a significant 15% deficit of all second cancers was observed [1,053 vs. 1,241; relative risk (RR) = 0.85; 95% CI = 0.80-0.90], most notably for respiratory (RR = 0.7) and digestive cancers (RR = 0.8). The absence of a colon cancer risk lends little support to the idea of common risk factors such as dietary fat consumption. Only the risk for salivary gland cancer was significantly increased, possibly due to chance. Leukemia was significantly elevated among men observed for 10 and more years (RR = 2.2). In contrast to most other index tumors, the prostate stands out as being associated with an overall low risk of second cancer development. The reasons for these deficiencies have not been explained. Among 1,446 men with testis cancer, a significant twofold risk of second cancers was seen (104 vs. 50.1). A fivefold risk of leukemia (8 vs. 1.5) was not related to treatment or age. Contralateral testis cancer (6 vs. 0.5) was elevated in men treated with and without radiation. Risks for kidney cancer (5 vs. 1.5), bladder cancer (9 vs. 3.4), pancreatic cancer (6 vs. 1.5), non-Hodgkin's lymphoma (6 vs. 1.5), and prostate cancer (12 vs. 5.9) were significantly increased. No trends over time were noted for any cancer. Overall risk of second cancer development tended to be higher in younger men with testis cancer. The relationship of leukemia to testis and prostate cancers should be investigated in future research.

Connecticut↗

Summary: multiple primary cancers in Connecticut, 1935-82.

The risk of developing a second primary cancer was evaluated in over 250,000 persons reported to the Connecticut Tumor Registry (CTR) during 1935-82. The CTR has collected data on cancer incidence longer than any other population-based tumor registry and thus provided researchers with a unique opportunity to investigate the occurrence of second cancers among persons followed for long periods, in some cases for more than 40 years. When compared with the general Connecticut population, cancer patients had a 31% increased risk of developing a subsequent cancer overall and a 23% elevated risk of second cancer at a different site from the first. Little variation in risk was seen for the first 20 years of follow-up, although the risk for females averaged twice that for males (41% vs. 18%). Persons who survived more than 20 years after the diagnosis of their first cancer were at highest risk: 51% for females and 45% for males. Over 1 million person-years of observation were recorded, and the excess risk of developing a new cancer was 3.5 per 1,000 persons per year. Common environmental exposures seemed responsible for the excess occurrence of many second cancers, particularly those related to cigarette smoking, alcohol consumption, or both. For example, persons with epithelial cancers of the lung, larynx, esophagus, buccal cavity, and pharynx were particularly prone to developing new cancers in the same or contiguous tissue throughout their lifetimes. A notable finding was the high risk of cancers of the lung, larynx, buccal cavity, and pharynx observed among cervical cancer patients, which suggested a common etiology involving cigarette smoking. The intriguing association previously reported among cancers of the colon, uterine corpus, breast, and ovary was confirmed in our data, which indicated the possible influence of hormonal or dietary factors. Incidental autopsy findings were largely responsible for the observed excesses of second cancers of the prostate and kidney, and heightened medical surveillance of cancer patients likely resulted in ascertainment bias and elevated risks for some tumors during the early period of follow-up, most notably cancers of the thyroid. Interestingly, patients with prostate cancer were the only ones found to be at significantly low risk for second cancer development. However, this might be an artifact of case-finding because advanced age at initial diagnosis of prostate cancer was associated with an underascertainment of second cancers.(ABSTRACT TRUNCATED AT 400 WORDS)

Connecticut↗

Introduction to the study of multiple primary cancers.

To lay the groundwork for subsequent chapters in this monograph of multiple primary cancers in Connecticut and Denmark, we present a description of the historical significance of previous studies, focusing on key surveys that have enhanced our understanding of the origins of multiple cancers. Case reports, hospital series, and cancer registry studies have progressively sharpened our perspective on the patterns and causes of multiple cancers. These findings in turn have generated hypotheses about host and environmental determinants of various combinations of cancer and have provided clues to the actual mechanisms of carcinogenesis. The registries of Connecticut and Denmark which began in the 1930s and 1940s, respectively, afford investigators a unique opportunity to analyze the cancer experience of well-defined populations, followed for long periods. The major contribution of this monograph is the evaluation of second cancer risks among long-term survivors of cancer, including relatively rare tumors about which little information currently exists. For patients with a particular cancer, the number of observed second cancers are tabulated over time and compared with those expected if the patients experienced the same rates prevailing in the corresponding general population. We have discussed problems in distinguishing statistical artifacts from biologically plausible associations in light of the potential biases inherent in follow-up surveys of cancer patients; for example, heightened medical surveillance and mistaken metastases could result in false indications of elevated risk. Several differences in the reporting, follow-up, and coding practices between the Connecticut and Denmark registries are described and probably account for many differences in the reported findings.(ABSTRACT TRUNCATED AT 250 WORDS)

Connecticut↗

Diazepam use and progression of breast cancer.

The relationship between diazepam and breast cancer was evaluated using data from a case-control study of breast cancer, in which 1075 cases and 1146 controls who were participants in a breast cancer screening program were interviewed. Diazepam use was negatively associated with extent of disease and lymph node involvement, and this effect seemed greatest for long-term users of diazepam. It is not certain to what extent these data reflect an ascertainment bias, an association with the reasons for which the drug was prescribed, or chance. Whatever the explanation, the findings do not support a previous contention that diazepam promotes or accelerates breast cancer growth.

Breast Neoplasms↗

Second cancers following radiotherapy for cervical cancer.

Incidence of second primary cancers was evaluated in 7,127 women with invasive cancer of the cervix uteri, diagnosed between 1935 and 1978, and followed up to 38 years (average, 8.9 yr) in Connecticut. Among 5,997 women treated with radiation, 449 developed second primary cancers compared with 313 expected (relative risk = 1.4) on the basis of rates from the Connecticut Tumor Registry. Excess incidence was noticeable 15 years or more after radiotherapy and attributed mostly to cancers of sites in or near the radiation field, especially the bladder, kidneys, rectum, corpus uteri, and ovaries. No excess was found for these sites among the 1,130 nonirradiated women. The ratio of observed to expected cancers for these sites did not vary appreciably by age at irradiation. The data suggested that high-dose pelvic irradiation was associated with increase in cancers of the bladder, kidneys, rectum, ovaries, corpus uteri, and non-Hodgkin's lymphoma but, apparently, not leukemia, Hodgkin's disease, breast cancer, or colon cancer.

Adult↗

Effect of methoxsalen photochemotherapy on cost of treatment for psoriasis. An example of technological assessment.

In 1974 a new therapy that employs methoxsalen and ultraviolet A irradiation (PUVA) was introduced as an outpatient treatment for severe psoriasis. To study the effect of this therapy on the cost of treatment, we documented for 1,320 patients two major components of cost--hospitalization and PUVA treatments. When the one-year period before initiation of PUVA therapy was compared with a one-year period after initiation of PUVA therapy, average hospital days per person per year declined 77% (5.1 vs 1.2). This decrease in hospitalization was most notable among patients who continued to use PUVA therapy. Largely offsetting the reduction in cost from reduced hospitalization was the cost of PUVA treatments. Our data confirm the previously known effectiveness of PUVA therapy, and they provide no support for the hypothesis that PUVA substantially increases the cost of treating patients with severe psoriasis.

Ambulatory Care↗

Phototoxic reactions to photoactive drugs in patients treated with PUVA.

To determine the potentially adverse effects of photoactive medications taken in conjunction with oral methoxsalen photochemotherapy (PUVA) for psoriasis, we studied the incidence of phototoxic reactions in 1,125 patients treated with PUVA at 15 centers. During the initial (clearing) phase of PUVA therapy, patients using photoactive medications were no more likely to have diffuse delayed erythema than patients who did not use such medications. After clearing, patients 45 years of age or older who used photoactive drugs were 2.3 times as likely to discontinue PUVA therapy for at least one month owing to problems related to UV-induced burns than were those who did not use such drugs. Only 6% of patients older than 45 years who took photoactive medications had problems with phototoxicity sufficiently severe to contribute to permanent discontinuation of PUVA therapy.

Adult↗

Risk of cutaneous carcinoma in patients treated with oral methoxsalen photochemotherapy for psoriasis.

A 2.1-year prospective study of 1373 patients given oral 8-methoxypsoralen photochemotherapy for psoriasis revealed 30 patients with a total of 48 basal-cell and squamous-cell carcinomas. The observed incidence of cutaneous carcinoma was 2.63 (95 per cent confidence limits = 1.91 to 3.90) times that expected for an age, sex and geographically matched population. Relative risk to patients with history of ionizing radiation was 3.68 (99 per cent confidence limits, 2.42 to 8.69). Patients with a previous cutaneous carcinoma had a relative risk of 10.22 (99 per cent confidence limits, 4.78 to 37.08). A higher than expected proportion of squamous-cell carcinomas and an excess of squamous-cell carcinomas in areas not exposed to sun were seen. New patients with known histories of ionizing-radiation exposure or of skin tumors should be given 8-methyoxypsoralen photochemotherapy only if they understand the risks and have disabling psoriasis untreatable by other means.

Administration, Oral↗

Antinuclear antibodies and oral methoxsalen photochemotherapy (PUVA) for psoriasis.

In view of theoretical concern that psoralen ultraviolet A radiation (PUVA) therapy might induce a systemic lupus erythematosus-like syndrome, we studied serum antinuclear antibodies (ANAs) in patients with psoriasis who received PUVA and are participating in a five-year prospective study. At 14 centers, 1,023 patients had two or more ANA determinations. When first and last tests were compared, the incidence of positive tests for ANAs was not significantly different (P greater than .2). In addition, there was no apparent relationship between the frequency of PUVA treatments and the probability of a positive test. Over a two-year period, there is no evidence to indicate that PUVA therapy for psoriasis has resulted in a significantly higher number of positive tests for ANAs within our population.

Adolescent↗

Multiple primary cancers in Connecticut, 1935-82.

Recently, the National Cancer Institute published a comprehensive monograph on multiple primary cancers in Connecticut and Denmark. This paper summarizes some of the observations made on the Connecticut population. Data compiled by the Connecticut Tumor Registry have extended our knowledge about the patterns of multiple primary cancers, especially among long-term survivors of cancer and among patients with relatively rare tumors about which little information currently exists. When compared with the general Connecticut population, cancer patients had a 31 percent (RR = 1.31) increased risk of developing a second cancer and a 23 percent (RR = 1.23) elevated risk of second cancer at a different site from the first. Common environmental exposures seemed responsible for the excess occurrence of many second cancers, particularly those related to cigarette smoking, alcohol consumption, or both. For example, persons with epithelial cancers of the lung, larynx, esophagus, buccal cavity, and pharynx were particularly prone to develop new cancers in the same or contiguous tissue throughout their lifetimes. Cancers of the colon, uterine corpus, breast, and ovary frequently occurred together, suggesting underlying hormonal or dietary influences. Only patients with prostate cancer were at significantly low risk for second cancer development; this might be an artifact of case finding, since advanced age at initial diagnosis was generally associated with an underascertainment of second cancers. Radiotherapy may have caused rectal and other cancer among patients with cancers of the female genital tract, and leukemia among patients with uterine corpus cancer. Chemotherapy with alkylating agents probably contributed to the excess of acute nonlymphocytic leukemia following multiple myeloma or cancers of the breast and ovary. Genetic susceptibility seemed to explain some tumor complexes, such as the multiple occurrences of cutaneous melanoma and the excess of bone cancer following retinoblastoma. Research into multiple cancer syndromes should enhance our understanding of carcinogenic factors and mechanisms and the development of strategies for cancer prevention and control.

Alcohol Drinking↗