Cancer Incidence and Mortality in Patients Treated Either With RAI or Thyroidectomy for Hyperthyroidism.

CONTEXT: Some previous studies have suggested increased cancer risk in hyperthyroid patients treated with radioactive iodine (RAI). It is unclear whether the excess cancer risk is attributable to hyperthyroidism, its treatment, or the shared risk factors of the two diseases. OBJECTIVE: The objective was to assess cancer morbidity and mortality in hyperthyroid patients treated with either RAI or surgery. PATIENTS: We identified 4334 patients treated surgically for hyperthyroidism in Finland during 1986-2007 from the Hospital Discharge Registry and 1814 patients treated with RAI for hyperthyroidism at Tampere University Hospital. For each patient, three age- and gender-matched controls were chosen. Information on cancer diagnoses was obtained from the Cancer Registry. The follow-up began 3 months after the treatment and ended at cancer diagnosis, death, emigration, or the common closing date (December 31, 2009). RESULTS: The overall cancer incidence was not increased among the hyperthyroid patients compared to their controls (rate ratio [RR], 1.05; 95% confidence interval [CI], 0.96-1.15). However, the risk of cancers of the respiratory tract (RR, 1.46; 95% CI, 1.05-2.02) and the stomach (RR, 1.64; 95% CI, 1.01-2.68) was increased among the patients. The overall cancer mortality did not differ between the patients and the controls (RR, 1.08; 95% CI, 0.94-1.25). The type of treatment did not affect the overall risk of cancer (hazard ratio for RAI vs thyroidectomy, 1.03; 95% CI, 0.86-1.23) or cancer mortality (hazard ratio, 1.04; 95% CI, 0.91-1.21). CONCLUSIONS: In this cohort of Finnish patients with hyperthyroidism treated with thyroidectomy or RAI, the overall risk of cancer was not increased, although an increased risk of gastric and respiratory tract cancers was seen in hyperthyroid patients. Based on this large-scale, long-term follow-up study, the increased cancer risk in hyperthyroid patients is attributable to hyperthyroidism and shared risk factors, not the treatment modality.

Cardiovascular morbidity and mortality in surgically treated hyperthyroidism - a nation-wide cohort study with a long-term follow-up.

OBJECTIVE: Previous studies suggest that patients with hyperthyroidism remain at an increased risk of cardiovascular morbidity even after restoring euthyroidism. The mechanisms of the increased risk and its dependency on the different treatment modalities of hyperthyroidism remain unclear. The aim of this long-term follow-up study was to compare the rate of hospitalizations for cardiovascular causes and the mortality in hyperthyroid patients treated surgically with an age- and gender-matched reference population. PATIENTS AND MEASUREMENTS: A population-based cohort study was conducted among 4334 hyperthyroid patients (median age 46 years) treated with thyroidectomy in 1986-2007 in Finland and among 12,991 reference subjects. Firstly, the hospitalizations due to cardiovascular diseases (CVD) were analysed until thyroidectomy. Secondly, the hazard ratios for any new hospitalization due to CVDs after the thyroidectomy were calculated in Cox regression analysis adjusted with the prevalent CVDs at the time of thyroidectomy. RESULTS: The risk of hospitalization due to all CVDs started to increase already 5 years before the thyroidectomy, and by the time of the operation, it was 50% higher in the hyperthyroid patients compared to the controls (P < 0·001). After the thyroidectomy, the hospitalizations due to all CVDs (HR 1·15), hypertension (HR 1·23), heart failure (HR 1·17) and valvular diseases or cardiomyopathies (HR 1·55) remained more frequent among the patients than among the controls for 20 years after thyroidectomy. The increased morbidity was not clearly related to the aetiology of hyperthyroidism. Despite the increased CVD morbidity among the patients, there was no difference in cardiovascular mortality. CONCLUSIONS: The present study shows that hyperthyroidism increases the risk of hospitalization due to CVDs and the risk is sustained up to two decades after effective surgical treatment. However, there was no excess CVD mortality in the middle-aged patient cohort studied.

Radiotherapy after segmental resection of breast cancer with favorable prognostic features: 12-year follow-up results of a randomized trial.

PURPOSE: Postoperative breast irradiation is considered standard after breast-preserving surgery for cancer. We evaluated the efficacy of radiation therapy in the prevention of local recurrence in a patient population that had small-size breast cancer with features that suggested low biologic aggressiveness. PATIENTS AND METHODS: Women (n = 264) older than 40 years who were treated by breast resection with > or = 1 cm of tumor-free margin and axillary nodal dissection were randomly assigned to receive or not to receive breast irradiation (cumulative dose, 50 Gy) after surgery. The tumor was required to be < or = 20 mm, node negative, progesterone receptor positive, well to moderately well differentiated and unifocal, and of low cell proliferation rate (ie, S phase fraction < or = 7% or nuclear Ki-67 expression < 10%) and had to lack an extensive intraductal component. The median follow-up time was 12.1 years after random assignment. RESULTS: Sixteen (11.6%) and 34 (27.2%) cancers recurred locally in the radiotherapy and the control arms, respectively (P = .0013). Time to local recurrence was longer in the radiotherapy arm (hazard ratio [HR], 0.36; 95% CI, 0.20 to 0.65; P = .00071). Twenty-one patients assigned to radiotherapy and 26 assigned to control died during the follow-up. There were no differences in overall survival time (HR, 0.63; 95% CI, 0.35 to 1.12; P = .11), distant disease-free survival (P = .94), or breast cancer-specific survival (P = .56) between the radiation therapy and control groups. CONCLUSION: Radiation therapy after breast resection reduces the frequency of ipsilateral breast recurrences, even among women with small-size breast cancers that have favorable histologic features and that are resected with at least a 1-cm margin. Postoperative radiotherapy did not significantly improve survival.

Factors determining esthetic outcome after breast cancer conservative treatment.

The aim of this study was to evaluate the factors that determine esthetic outcome after breast cancer conservative treatment, based on a consensual classification obtained with an international consensus panel. Photographs were taken from 120 women submitted to conservative unilateral breast cancer surgery (with or without axillary surgery) and radiotherapy. The images were sent to a panel of observers from 13 different countries and consensus on the classification of esthetic result (recorded as excellent, good, fair or poor) was obtained in 113 cases by means of a Delphi method. For each patient, data were collected retrospectively regarding patient characteristics, tumor, and treatment factors. Univariate and multivariate analysis were used to evaluate the correlation between these factors and overall cosmetic results. On univariate analysis, younger and thinner patients as well as patients with lower body mass index (BMI) and premenopausal status obtained better cosmetic results. In the group of tumor- and treatment-related factors, larger removed specimens, clearly visible scars, the use of chemotherapy and longer follow-up period were associated with less satisfactory results. On multivariate analysis, only BMI and scar visibility maintained a significant association with cosmesis. BMI and scar visibility are the only factors significantly associated with cosmetic results of breast cancer conservative treatment, as evaluated by an international consensus panel.

Is bile flow reduced in patients with hypothyroidism?

BACKGROUND: Disturbances in the sphincter of Oddi (SO) function may prevent normal bile flow and thus enhance the probability of common bile duct stone (CBDS) formation. We have previously shown increased prevalence of diagnosed hypothyroidism in CBDS patients, thyroxine (T(4)) -induced inhibition of the SO contractility both in animal and in human experiments ex vivo, and reduced bile flow to duodenum in hypothyroid rats. The aim of the present study was to investigate human biliary dynamics in relation to altered thyroid gland function. METHODS: Eight female patients, 1 with diagnosed untreated hypothyroidism and 7 with total thyroidectomy performed due to thyroid cancer, were studied in hypothyroid stage and again after thyroxine replacement therapy in euthyroid stage, with quantitative (99m)Tc HIDA cholescintigraphy (QC), biliary ultrasonography, and serum determinations. Each patient served as her own control in the 2 stages of the study. RESULTS: In QC, maximal uptake of (99m)Tc HIDA was not changed in hypothyroidism compared to euthyroidism. The first appearance of radioactivity to large bile ducts at the hepatic hilum remained unchanged in the 2 stages of the study. Hepatic clearance of (99m)Tc HIDA was decreased at 45 minutes (28% [11-38] vs 50% [33-54]; P =.028; median and range) and at 60 minutes (55% [28-80] vs 69% [61-79]; P =.028; median and range) and hilum-duodenal transit time increased by 31% compared to euthyroid stage. In US no changes were seen in gall bladder or bile ducts in the 2 stages of the study. Serum hypercholesterolemia was observed in the hypothyroid stage. CONCLUSIONS: We conclude that hypothyroidism may result in delayed emptying of the biliary tract, as studied with QC. In addition to the changes in bile composition and excretion rate suggested before to take place in hypothyroidism, according to the present study changes in biliary emptying also may be included in the probable causes for the increased prevalence of CBDS in hypothyroidism. This may be due to the absence of the prorelaxing effect of thyroxine on SO, which we have shown before to exist ex vivo.

An in vitro long-term culture model for normal human mammary gland: expression and regulation of steroid receptors.

Steroids and their nuclear receptors play crucial roles in the development and maintenance of normal functions of the human mammary gland (HMG). They have also been implicated in breast carcinogenesis. However, the study of steroid action in normal HMG has been hampered by experimental difficulties. By using a newly established in vitro long-term culture method, we successfully cultured normal HMG tissue for more than 2 months without detriment to its morphology or steroid receptor expression. Expression of the cellular structural and extracellular matrix proteins was similar to that prior to culture, and HMG tissue retained its properties of steroid receptor expression and regulation. Addition of 17-beta estrogen to mammary tissues markedly increased the expression of progesterone receptor (PR) but only slightly affected that of the estrogen receptor (ER). Medroxyprogesterone acetate down-regulated the expression of PR within 24-48 h and also increased the expression of androgen receptor. When HMG tissue was cultured in medium containing normal or dextran-coated charcoal-stripped fetal calf serum or normal human serum, the expression and regulation of steroid hormone receptors were similar, although different in extent. When serum was omitted, the morphology of HMG was normal after 1 week, but the expression and regulation of ER and PR were altered. Thus, as HMGs retain the capacity to express steroid receptors in culture, this long-term culture system is probably a good model for studying the regulation of the mammary gland by steroids.

Intraoperative localization of parathyroid glands with gamma counter probe in primary hyperparathyroidism: a prospective study.

BACKGROUND: Technetium 99m-sestamibi imaging might be the best method to localize abnormal parathyroid glands. No studies to date have compared preoperative imaging and intraoperative gamma probe localization in patients with primary hyperparathyroidism. STUDY DESIGN: This prospective study included 20 arbitrarily selected patients with primary hyperparathyroidism, verified by elevated serum ionized calcium and intact parathyroid hormone concentrations and low serum phosphatase level. Each patient underwent both preoperative imaging study of the parathyroid glands with technetium 99m-sestamibi (dose 740MBq) and intraoperative localization with a handheld gamma probe. Full collar exploration served as the gold standard. RESULTS: Hypercalcemia and hypophosphatemia normalized in each patient. A single parathyroid adenoma was confirmed histologically in 16 and hyperplasia (4 abnormal glands) in 4 patients. None of the patients had multiple adenomas. The sensitivity of the preoperative scan was 81% (13 of 16 patients) in adenoma patients and 100% (4 of 4 patients) in hyperplasia. The corresponding specificity was 88% and 100%. Intraoperatively only 8 of 16 adenomas were correctly detected (sensitivity 50%), and none of the hyperplastic glands were correctly detected. CONCLUSIONS: In unselected patients with primary hyperparathyroidism, preoperative technetium 99m-sestamibi imaging is more accurate than intraoperative gamma probe detection in localizing abnormal parathyroid glands.