Donald F. Austin

Early menopause in long-term survivors of cancer during adolescence

Objective: We attempted to investigate the risk of early menopause after treatment for cancer during childhood or adolescence. Study Design: We interviewed 1067 women in whom cancer was diagnosed before age 20, who were at least 5-year survivors, and who were still menstruating at age 21. Self-reported menopause status in survivors was compared with that in 1599 control women. Results: Cancer survivors, with disease diagnosed between ages 13 and 19, had a risk of menopause four times greater than that of controls during the ages 21 to 25; the risk relative to controls declined thereafter. Significantly increased relative risks of menopause during the early 20s occurred after treatment with either radiotherapy alone (relative risk 3.7) or alkylating agents alone (relative risk 9.2). During ages 21 to 25 the risk of menopause increased 27-fold for women treated with both radiation below the diaphragm and alkylating agent chemotherapy. By age 31, 42% of these women had reached menopause compared with 5% for controls. Conclusions: Treatment for cancer during adolescence carries a substantial risk for early menopause among women still menstruating at age 21. Increasing use of radiation and chemotherapy, together with the continued trend toward delayed childbearing, suggests that these women should be made aware of their smaller window of fertility so that they can plan their families accordingly.

Radiation dose and second cancer risk in patients treated for cancer of the cervix

The risk of cancer associated with a broad range of organ doses was estimated in an international study of women with cervical cancer. Among 150,000 patients reported to one of 19 population-based cancer registries or treated in any of 20 oncology clinics, 4188 women with second cancers and 6880 matched controls were selected for detailed study. Radiation doses for selected organs were reconstructed for each patient on the basis of her original radiotherapy records. Very high doses, on the order of several hundred gray, were found to increase the risk of cancers of the bladder [relative risk (RR) = 4.0], rectum (RR = 1.8), vagina (RR = 2.7), and possibly bone (RR = 1.3), uterine corpus (RR = 1.3), cecum (RR = 1.5), and non-Hodgkins lymphoma (RR = 2.5). For all female genital cancers taken together, a sharp dose-response gradient was observed, reaching fivefold for doses more than 150 Gy. Several gray increased the risk of stomach cancer (RR = 2.1) and leukemia (RR = 2.0). Although cancer of the pancreas was elevated, there was no evidence of a dose-dependent risk. Cancer of the kidney was significantly increased among 15-year survivors. A nonsignificant twofold risk of radiogenic thyroid cancer was observed following an average dose of only 0.11 Gy. Breast cancer was not increased overall, despite an average dose of 0.31 Gy and 953 cases available for evaluation (RR = 0.9); there was, however, a weak suggestion of a dose response among women whose ovaries had been surgically removed. Doses greater than 6 Gy to the ovaries reduced breast cancer risk by 44%. A significant deficit of ovarian cancer was observed within 5 years of radiotherapy; in contrast, a dose response was suggested among 10-year survivors. Radiation was not found to increase the overall risk of cancers of the small intestine, colon, ovary, vulva, connective tissue, breast, Hodgkins disease, multiple myeloma, or chronic lymphocytic leukemia. For most cancers associated with radiation, risks were highest among long-term survivors and appeared concentrated among women irradiated at relatively younger ages.

Genetic Disease in Offspring of Long-Term Survivors of Childhood and Adolescent Cancer

Numerous case series have addressed the concern that cancer therapy may damage germ cells, leading to clinical disease in offspring of survivors. None has documented an increased risk. However, the methodological problems of small series make it difficult to draw firm conclusions regarding the potential of cancer treatments to damage the health of future offspring. We conducted a large interview study of adult survivors of childhood cancer treated before 1976. Genetic disease occurred in 3.4% of 2,198 offspring of survivors, compared with 3.1% of 4,544 offspring of controls (P=.33; not significant); there were no statistically significant differences in the proportion of offspring with cytogenetic syndromes, single-gene defects, or simple malformations. A comparison of survivors treated with potentially mutagenic therapy with survivors not so treated showed no association with sporadic genetic disease (P=.49). The present study provides reassurance that cancer treatment using older protocols does not carry a large risk for genetic disease in offspring conceived many years after treatment. With 80% power to detect an increase as small as 40% in the rate of genetic disease in offspring, this study did not do so. However, we cannot rule out the possibility that new therapeutic agents or specific combinations of agents at high doses may damage germ cells.

Mycobacterial diseases and antitumour necrosis factor therapy in USA

Objective In North America, tuberculosis and nontuberculous mycobacterial (NTM) disease rates associated with antitumour necrosis factor α (anti-TNFα) therapy are unknown. Methods At Kaiser Permanente Northern California, the authors searched automated pharmacy records to identify inflammatory disease patients who received anti-TNF therapy during 2000–2008 and used validated electronic search algorithms to identify NTM and tuberculosis cases occurring during anti-TNF drug exposure. Results Of 8418 anti-TNF users identified, 60% had rheumatoid arthritis (RA). Among anti-TNF users, 18 developed NTM and 16 tuberculosis after drug start. Anti-TNF associated rates of NTM and tuberculosis were 74 (95% CI: 37 to 111) and 49 (95% CI: 18 to 79) per 100 000 person-years, respectively. Rates (per 100, 000 person-years) for NTM and tuberculosis respectively for etanercept were 35 (95% CI: 1 to 69) and 17 (95% CI: 0 to 41); infliximab, 116 (95% CI: 30 to 203) and 83 (95% CI: 10 to 156); and adalimumab, 122 (95% CI: 3 to 241) and 91 (95% CI: 19 to 267). Background rates for NTM and tuberculosis in unexposed RA-patients were 19.2 (14.2 to 25.0) and 8.7 (5.3 to 13.2), and in the general population were 4.1 (95% CI 3.9 to 4.4) and 2.8 (95% CI 2.6 to 3.0) per 100, 000 person-years. Among anti-TNF users, compared with uninfected individuals, NTM case-patients were older (median age 68 vs 50 years, p<0.01) and more likely to have RA (100% vs 60%, p<0.01); whereas, tuberculosis case-patients were more likely to have diabetes (37% vs 16%, p=0.02) or chronic renal disease (25% vs 6%, p=0.02). Conclusions Among anti-TNF users in USA, mycobacterial disease rates are elevated, and NTM is associated with RA.

CANCER IN OFFSPRING OF LONG-TERM SURVIVORS OF CHILDHOOD AND ADOLESCENT CANCER

A multicentre retrospective cohort study of long-term survivors of childhood and adolescent cancer identified 7 cases of cancer among 2308 offspring (0.30%) of 2283 case-survivors and 11 cases among 4719 offspring (0.23%) of 3604 controls. Overall, the observed numbers of cases were not significantly different from those expected in the general population. Among offspring of case-survivors observed for the first 5 years of life, the group with the most person-years of follow-up, 5 cancers were reported (3 confirmed), compared with 1.7 expected, a significant excess due mostly to boys whose mothers survived cancer. Some offspring with cancer had known single-gene traits; others resembled previously recognised patterns of family cancer. The remainder may represent chance occurrences or new cancer family syndromes, such as an association with malignant melanoma. The study had an overall 79% power to detect a 3-fold excess of cancer among offspring of case-survivors, but no excess was observed. The number person-years of follow-up in the second decade of life, when most cases of cancer developed, was small.

Incidence and prevalence of uveitis in Veterans Affairs Medical Centers of the Pacific Northwest.

PURPOSE To ascertain the frequency of uveitis in Veterans Affairs (VA) patients in the Pacific Northwest and to compare disease rates with those in previously published epidemiologic studies. DESIGN Cross-sectional, population based-study. METHODS The medical records of 152,267 patients seen at six VA Medical Centers in Oregon and Washington during fiscal year 2004 were searched for uveitis-related International Classification of Diseases 9th edition codes. Cases were reviewed and classified anatomically, by associated systemic disease, and as incident or prevalent. Only definite cases were used for disease rate calculations. RESULTS This study found a crude incidence of 25.6 cases/100,000 person-years and a crude prevalence of 69 cases/100,000 persons. The most common anatomic location for uveitis was anterior. Approximately half of cases were idiopathic, with human leukocyte antigen-B27-related diseases being the most common identified cause. There was no statistical evidence of increased or decreased incidence with age, although uveitis seemed to be more prevalent in the younger age groups. CONCLUSIONS Our data are consistent with those of most published population-based studies on the epidemiologic features of uveitis, but we detected significantly lower incidence and prevalence than those reported in a recently published study from Kaiser Permanente. The significance of and possible explanations for the differences between our data and that published by the Kaiser group are discussed.

Histologic types and hormone receptors in breast cancer in men: a population-based study in 282 United States men

Histologic slides from 282 incident cases of breast cancer in men, that were identified in 10 population-based cancer registries in the United States, were reviewed by a single pathologist. Breast cancer more often presented in the noninvasive stage in men (10.8 percent of all cases) than would be expected among women. All noninvasive carcinomas were of the ductal type. Of invasive carcinomas, compared with women, men had smaller proportions of lobular and mucinous types and larger proportions of ductal and papillary types and Pagets disease. No case of tubular or medullary carcinoma was seen. The breast in men is composed only of ducts and normally contains no lobules, and the histologic types of breast carcinomas that predominate in men are likely of ductal origin. Estrogen and progesterone receptors were present in 86.7 percent and 76.3 percent of invasive carcinomas, respectively, which are higher proportions than would be expected among women. Also, unlike findings in women, receptor content was not associated with patient age at diagnosis.

Evolving Preoperative Evaluation of Patients with Pancreatic Cancer: Does Laparoscopy Have a Role in the Current Era?

BACKGROUND Recent years have brought important developments in preoperative imaging and use of laparoscopic staging of patients with pancreatic adenocarcinoma (PAC). There are few data about the optimal combination of preoperative studies to accurately identify resectable patients. STUDY DESIGN We conducted a statewide review of all patients with surgically managed PAC from 1996 to 2003 using data from the Oregon State Cancer Registry, augmented with clinical information from primary medical record review. We documented the use of all staging modalities, including CT, endoscopic ultrasonography, and laparoscopy. Primary outcomes included resection with curative intent. The association between staging modalities, clinical features, and resection was measured using a multivariate logistic regression model. RESULTS There were 298 patients from 24 hospitals who met the eligibility criteria. Patients were staged using a combination of CT (98%), laparoscopy (29%), and endoscopic ultrasonography (32%). The overall proportion of patients who went to surgical exploration and were resected was 87%. Of patients undergoing diagnostic laparoscopy, metastatic disease that precluded resection was discovered in 24 (27.6%). For patients who underwent diagnostic laparoscopy and were not resected, vascular invasion was the most common determinant of unresectability (56.6%). In multivariate analysis, preoperative weight loss and surgeon decision to use laparoscopy predicted unresectability at laparotomy. CONCLUSIONS This population-based study demonstrates that surgeons appear to use laparoscopy in a subset of patients at high risk for metastatic disease. The combination of current staging techniques is associated with a high proportion of resectability for patients taken to surgical exploration. With current imaging modalities, selective application of laparoscopy with a dual-phase CT scan as the cornerstone of staging is a sound clinical approach to evaluate pancreatic cancer patients for potential resectability.

Diabetes-related changes in hearing†

Determine the effects on hearing of diabetes mellitus (DM) severity.

Oral and pharyngeal cancer and occupation: A case-control study

We studied the relation between occupation and oral and pharyngeal cancer with a population-based case-control study conducted in four areas of the United States. The study group included 1,114 incident male and female cases and 1,268 frequency-matched controls. After adjustment for age, race, smoking, alcohol, and study location, an analysis of lifetime occupational histories revealed a small number of noteworthy associations. Risk was increased among male carpet installers (23 cases, 4 controls), with an adjusted odds ratio of 7.7 [95% confidence interval (CI)=2.4−24.91, and tended to rise with longer duration of employment. A decreased risk was found among male and female textile mill workers (odds ratio 0.48, 95% CI=0.27−0.88). Previously reported increases in oral cancer risks among printing workers, electrical and electronics workers, and workers other than carpet installers who were possibly exposed to formaldehyde were not found in this study. For several employment groups, including male machinists, primary metal industry workers, petroleum industry workers, painters, furniture and fixture industry workers, woodworking machine operators, and workers with inferred exposure to fossil fuel combustion, odds ratios were approximately 2.0 for cancers of pharyngeal sites. (Epidemiology 1992;3:300–309)