Dimitrios Linos

A pooled analysis of case-control studies of thyroid cancer II. Menstrual and reproductive factors

Objective: It has been suggested that female hormones, and hence menstrual and reproductive factors, play a role in thyroid cancer etiology. Epidemiological data, however, are limited and inconsistent, partly because of the small number of cases included in each study. To clarify the etiology of thyroid cancer, we conducted a pooled analysis of original data from 14 case-control studies, 4 from the United States, 2 from Asia, and 8 from Europe.Methods: This analysis included a total of 2,247 female cases of thyroid cancer (80% papillary) and 3,699 control women. Pooled odds ratios (OR) were estimated using logistic regression, conditioning on study and (i) matching sets for individually matched studies, or (ii) quinquennia of age for the other studies. Additional terms for age and history of radiation exposure were included in the regression equations.Results: The OR per year of later menarche was 1.04 (95% confidence interval (CI) 1.0–1.1). Compared to pre-menopausal women, the OR was 1.3 for women with natural menopause, and 1.8 for those with artificial menopause, but the studies were heterogeneous and the association may be due, at least in part, to diagnostic or ascertainment bias. Parity, spontaneous or induced abortions and history of infertility were not associated with thyroid cancer risk. The OR was above unity in women reporting later age at first birth (OR=1.1, 95% CI 1.0–1.3 for 5-year delay) and higher in the first years after a birth.Conclusions: The associations of menstrual and reproductive factors with thyroid cancer risk were generally weak, but appeared stronger among women diagnosed with thyroid cancer at younger ages.

A POOLED ANALYSIS OF CASE-CONTROL STUDIES OF THYROID CANCER. IV. BENIGN THYROID DISEASES

Objective: To obtain more precise estimates of the association between thyroid cancer and benign thyroid diseases and to elucidate the role of potential confounders or effect modifiers.Methods: The original data from 12 case–control studies from the United States, Asia, and Europe were pooled. Based on 2094 women and 425 men with cancer of the thyroid and, respectively, 3248 and 928 control subjects, odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were obtained by conditional regression models, conditioning on study and age at diagnosis, and adjusting for age and radiotherapy.Results: A history of hypothyroidism was not associated with cancer risk (pooled ORs = 0.9, 95% confidence interval, CI: 0.7–1.3 in women and 1.7, 95% CI: 0.3–11.7 in men). ORs for hyperthyroidism were 1.4 (95% CI: 1.0–2.1) in women and 3.1 (95% CI: 1.0–9.8) in men. In women, however, risk was lower in the absence of or after allowance for history of goiter. Pooled ORs for a history of goiter were 5.9 (95% CI: 4.2–8.1) in women and 38.3 (95% CI: 5.0–291.2) in men. Risk for a history of benign nodules/adenomas was especially high (OR = 29.9, 95% CI: 14.5–62.0, in women; 18 cases versus 0 controls in men). The excess risk for goiter and benign nodules/adenomas was greatest within 2–4 years prior to thyroid cancer diagnosis, but an elevated OR was present 10 years or more before cancer.Conclusions: Goiter and benign nodules/adenomas are the strongest risk factors for thyroid cancer, apart from radiation in childhood.

Reinforcement Does Not Necessarily Reduce the Rate of Staple Line Leaks After Sleeve Gastrectomy. A Review of the Literature and Clinical Experiences

BackgroundLaparoscopic sleeve gastrectomy (SG) is an accepted bariatric procedure, with an advantaged by a low complication rate. A feared complication is stapler line leak. Buttressing materials have been suggested as a means of reducing staple line leak rates. We analyzed the leak rates from published series to help in demonstrating a potential cause.MethodsThe study was institutional review board (IRB) approved retrospectively. A Medline search using the key words sleeve gastrectomy and bariatric surgery obtained 54 articles. Attention was restricted to 11 articles written in English that listed numbers of gastrectomy procedures and leaks. Poisson regression assessed the possibility that patients who received buttressing materials had a reduced rate of leaks.ResultsThirty-five patients were evaluated from Greece (15) and the United States (20); two patients developed staple line leaks that appeared to be related to problems associated with buttressing materials. Eleven prior studies and the present series yielded 1,589 procedures, 15 (0.94%) of which were complicated by leaks. The leak rate for patients who were known to have received reinforcement of some sort was 1.45 (95% confidence interval 0.41–3.43) times that for other patients. To detect a difference between 1% and 0.5% as statistically significant in 80% of cases, with a two tailed test and alpha set at 0.05, would require 9,346 procedures.ConclusionsThere is no reason to believe, at this point, that reduction in leak rates occur because reinforcement is used. Because the leak rate is small, the routine reinforcement of the staple line after sleeve gastrectomy is questionable at best, although a decrease in hemorrhage has been reported.

Primary hepatic lymphoma: a review

Primary lymphoma of the liver is extremely rare, and is more common among immunocompromised patients. It typically occurs during the fifth decade of life and has a male predominance. Abdominal pain, weight loss, and fever are the normal symptoms. Liver function tests are usually upset. Ultrasonography, computed tomography, and magnetic resonance imaging can help in the diagnosis, which can be confirmed only by histological examination of a liver biopsy specimen. Treatments include surgery, chemotherapy, and radiotherapy all of which give good results. Surgical resection when feasible is beneficial.

A pooled analysis of thyroid cancer studies. V. Anthropometric factors

AbstractObjective: To assess the relation between anthropometric factors and thyroid cancer risk in a pooled analysis of individual data from 12 case–control studies conducted in the US, Japan, China and Europe. Methods: 2056 female and 417 male cases, 3358 female and 965 male controls were considered. Odds ratios (OR) were derived from logistic regression, conditioning on age, A-bomb exposure (Japan) and study, and adjusting for radiotherapy. Results: Compared to the lowest tertile of height, the pooled OR was 1.2 for females for the highest one, and 1.5 for males, and trends in risk were significant. With reference to weight at diagnosis, the OR for females was 1.2 for the highest tertile, and the trend in risk was significant, whereas no association was observed in males. Body mass index (BMI) at diagnosis was directly related to thyroid cancer risk in females (OR = 1.2 for the highest tertile), but not in males. No consistent pattern of risk emerged with BMI during the late teens. Most of the associations were observed both for papillary and follicular cancers, and in all age groups. However, significant heterogeneity was observed across studies. Conclusions: Height and weight at diagnosis are moderately related to thyroid cancer risk.

A pooled analysis of case-control studies of thyroid cancer. III. Oral contraceptives, menopausal replacement therapy and other female hormones.

Objective: The relations between oral contraceptives (OC), hormone replacement therapy (HRT) for menopause, and other female hormone use and thyroid cancer risk was analyzed using the original data from 13 studies from North America, Asia and Europe.Methods: Based on 2,132 cases and 3,301 controls, odds ratios (OR) and the corresponding 95% confidence intervals (CI) were obtained by conditional regression models, conditioning on study and age at diagnosis, and adjusting for age, radiation exposure and parity.Results: Overall, 808 (38%) cases versus 1,290 (39%) controls had ever used OCs, corresponding to an OR of 1.2 (95% CI 1.0 to 1.4). There was no relation with duration of use, age at first use, or use before first birth. The OR was significantly increased for current OC users (OR=1.5, 95% 1.0 to 2.1), but declined with increasing time since stopping (OR=1.1 for >10 years since stopping). The association was stronger for papillary cancers (OR=1.6 for current users) than for other histologic types. No significant heterogeneity was observed across studies or geographic areas. Eight studies had data on HRT, for a total of 1,305 cases and 2,300 controls: 110 (8%) cases and 205 (9%) controls reported ever using HRT (OR=0.8; 95% CI 0.6 to 1.1). The ORs were 1.6 (95% to 0.9 to 2.9) for use of fertility drugs, and 1.5 (95% CI 1.1 to 2.1) for lactation suppression treatment.Conclusions: The studies considered in these analyses include most of the epidemiological data on the role of exogenous hormone use in the etiology of thyroid cancer, and they provide reassuring evidence on the absence of an association of practical relevance. The moderate excess risk in current OC users, if not due to increased surveillance for thyroid masses among OC users, is similar to that described for breast cancer, and would imply a role of female hormones on thyroid cancer promotion. There was no indication of increased thyroid cancer risk 10 or more years after discontinuing OC use.

A pooled analysis of case-control studies of thyroid cancer. VI. Fish and shellfish consumption

Objective: To better understand the role of fish and shellfish on thyroid cancer risk, we systematically re-analyzed the original data from 13 case–control studies conducted in the US, Japan, China, and Europe. Methods: A total of 2497 cases (2023 women, 474 men) and 4337 controls (3268 women, 1069 men) were considered. Odds ratio (OR) and corresponding 95% confidence interval (CI) were estimated for each study by logistic regression models, conditioned on age and sex, and adjusted for history of goiter, thyroid nodules or adenomas, and radiation. Combined ORs were computed as the weighted average of the estimates from each study. Results: The ORs for the highest level of total fish consumption (three or more times per week) as compared to the lowest one (less than once per week) was above unity in Hawaii, Connecticut, Japan, Norway, Tromsø, and Vaud. Conversely, the ORs for the studies in Los Angeles, Shanghai, southeastern Sweden, Uppsala, northern Sweden, northern Italy, and Athens were below one. The pattern of risk for salt water fish and shellfish was not substantially different from that of total fish. Fish was not associated with thyroid cancer risk in all studies combined (OR=0.99, 95% CI 0.85–1.2 for moderate, and OR=0.88, 95% CI 0.71–1.1 for high total fish consumption), but there was a suggestion of a protective effect in endemic goiter areas (OR=0.65, 95% CI 0.48–0.88). Conclusion: This combined analysis indicates that relatively elevated fish consumption does not appreciably increase thyroid cancer risk, and may have a favorable influence in areas where iodine deficiency is, or was, common.

The influence of dietary patterns on the development of thyroid cancer.

To elucidate the role of diet in the development of thyroid cancer, we conducted a case-control study of 113 persons with histologically-verified thyroid cancer and 138 controls, matched by age, gender and health unit. Socio-economic data, known risk factors and food consumption of more than 100 items were recorded by interviewer-administered prestructured questionnaire. Factor analysis was used to identify possible dietary patterns and logistic regression analysis was used to explore the effect of food items or dietary patterns on thyroid cancer. After adjustment for age, gender, body mass index (BMI), and total energy intake, significant positive associations were observed for pork consumption, while negative ones were observed for tomatoes, lemons and pasta. Dietary patterns of fruits, raw vegetables and mixed raw vegetables and fruits, led to a reduced risk (corresponding odds ratios (ORs) 0.68, 0.71, 0.73) for all thyroid cancers and similar figures were obtained for papillary thyroid cancers. A dietary pattern of fish and cooked vegetables led to an increased risk (OR 2.79) of follicular cancer.

Adrenaloma: a call for more aggressive management.

Abstract. We review our experience from the surgical management of 57 patients (24 males, 33 females) with a mean age of 48.5 years who underwent adrenalectomy because of the computed tomography (CT) finding of a “nonfunctioning” adrenal tumor (adrenaloma). We found that CT consistently underestimated the real histologic size of the adrenal tumor (p = 0.001). Of the 57 resected tumors, 23 were cortical adenomas, 7 myelolipomas, 8 adrenal cysts, 11 nodular hyperplasias, 2 primary adenocarcinomas, 2 metastatic carcinomas, and 4 pheochromocytomas. The mean diameter was 5.89 cm and the mean weight 114.07 g. The mean diameter of the resected primary adenocarcinomas was 3.0 cm and 4.5 cm, respectively. The operative mortality was zero and the perioperative morbidity minimal. The mean operating time was 137 minutes (range 60–240 minutes). The posterior approach had the shortest operating time and the laparoscopic approach the shortest hospital stay and the least postoperative need for narcotics. During the 6.2 years mean follow-up period, five patients with preoperative hypertension remained normotensive, and both patients with the resected primary adenocarcinomas are alive without recurrence. We suggest a more liberal surgical approach to patients with adrenalomas because: (1) even small tumors can be malignant or potentially lethal (e.g., pheochromocytomas); (2) some tumors that appear to be nonfunctioning may in reality be functioning; and (3) other nonfunctioning tumors may, with time (and without prior notice), function. The low risk of adrenalectomy especially via the laparoscopic approach can provide an early definitive diagnosis and treatment, avoiding the cost of repeated CT scans and other studies as suggested by the currently prevailing conservative management of these tumors.

A pooled analysis of case-control studies of thyroid cancer. VII. Cruciferous and other vegetables (International)

OBJECTIVE: To investigate the association between cruciferous and other vegetables and thyroid cancer risk we systematically reanalyzed the original data from 11 case–control studies conducted in the US, Asia, and Europe.METHODS: A total of 2241 cases (1784 women, 457 men) and 3716 controls (2744 women, 972 men) were included. Odds ratios (OR) and the corresponding 95% confidence intervals (CI) were estimated for each study by logistic regression models, conditioned on age and sex, and adjusted for history of goiter, thyroid nodules or adenomas, and radiation. Summary ORs for all studies combined were computed as the weighted average of the estimates from each study.RESULTS: A decreased risk for the highest level of cruciferous vegetable intake, as compared to the lowest, was observed in Los Angeles, Hawaii, Connecticut, southeastern Sweden, Tromsø, and Switzerland; the OR were above unity in Japan and Uppsala, whereas no material association was found in northern Sweden, Italy, or Greece. The OR values for all studies combined were 0.87 (95% CI 0.75–1.01) for moderate and 0.94 (95% CI 0.80–1.10) for high cruciferous vegetables intake. The results were similar in studies from iodine-rich areas and endemic goiter areas, and were consistent when the analysis was restricted to papillary carcinomas and women. The summary OR values for vegetables other than cruciferous were 1.04 (0.88–1.22) for moderate and 0.82 (0.69–0.98) for high consumption.CONCLUSIONS: This combined analysis indicates that cruciferous vegetables are not positively related to thyroid cancer risk. Their effect does not seem to be substantially different from that of other vegetables, which appear to be protective on this cancer.