Low-Activity Radioactive Iodine Therapy for Thyroid Carcinomas Exhibiting Nodal Metastases and Extrathyroidal Extension May Lead to Early Disease Recurrence.

BACKGROUND: The application of radioactive iodine in differentiated thyroid carcinomas has become more selective in an attempt to decrease morbidity. While ablative success has been documented, it is less clear how changes in radioactive iodine treatment strategies will influence long-term recurrence rates for patients with larger tumors and adverse pathological features, including extrathyroidal extension and nodal metastases. METHODS: Patients diagnosed between 1995 and 2008 with differentiated thyroid carcinoma treated with thyroidectomy followed by radioactive iodine treatment were eligible. All patients were followed for a minimum of five years using a standardized follow-up protocol requiring both biochemical and imaging assessments for recurrent disease (n = 219). Patients were stratified by initial radioactive iodine activity, and disease-free survival was calculated using the Kaplan-Meier method, with significant differences defined by the log-rank test. RESULTS: In this cohort, 46% of patients had clinical metastases and 74% had primary tumors >1.5 cm. Patients who had recurrences were more likely to present with extrathyroidal extension (p = 0.002) and lymph node metastases at diagnosis (p < 0.001). Patients presenting with both extrathyroidal extension and lymph node metastases had a significantly worse time to progression if treated with <1850 MBq radioactive iodine compared to those patients treated with >1850 MBq (25 months vs. 121 months; p = 0.004). The use of lower-activity radioactive iodine ablative therapy was associated with more early recurrences (p = 0.003). Being aged younger or older than 45 years did not impact the time to recurrence nor did the use of level 6 dissection. On multivariate analysis, lymph node metastases at diagnosis and multiple applications of radioactive iodine were linked to increased risk of recurrence. Patients with neither, or only one, adverse pathologic feature had excellent outcomes, regardless of initial ablative activity, with <10% of patients recurring over a 10-year time span. CONCLUSIONS: Recurrent disease in differentiated thyroid carcinoma is more common in patients treated with low-activity radioactive iodine in patients with lymph node metastases and extrathyroidal extension. These recurrences typically occur within four years of initial treatment. Patients lacking both of these risk factors treated with low radioactive iodine activity (<1850 MBq) have excellent outcomes, even after 10 years.

131I-MIBG Therapy in a Metastatic Small Bowel Neuroendocrine Tumor Patient Undergoing Hemodialysis.

Systemic radioisotope therapy with I-metaiodobenzylguanidine (I-MIBG) is an effective form of targeted therapy for neuroendocrine tumors. One of the absolute contraindications to administering I-MIBG therapy listed in the 2008 European Association of Nuclear Medicine guidelines is renal insufficiency requiring dialysis, although this contraindication is not evidence based. We describe a 68-year-old woman with a metastatic small bowel neuroendocrine tumor who developed renal insufficiency requiring hemodialysis. Imaging and dosimetry with I-MIBG were performed and showed that the radiation doses to the whole body and lungs were within safe limits. She was treated with 1820 MBq of I-MIBG with no short-term adverse reactions.

Multifaceted support for a new medical school in Nepal devoted to rural health by a Canadian Faculty of Medicine and Dentistry.

Nepal and Alberta are literally a world apart. Yet they share a common problem of restricted access to health services in remote and rural areas. In Nepal, urban-rural disparities were one of the main issues in the recent civil war, which ended in 2006. In response to the need for improved health equity in Nepal a dedicated group of Nepali physicians began planning the Patan Academy of Health Sciences (PAHS), a new health sciences university dedicated to the education of rural health providers in the early 2000s. Beginning with a medical school the Patan Academy of Health Sciences uses international help to plan, deliver and assess its curriculum. PAHS developed an International Advisory Board (IAB) attracting international help using a model of broad, intentional recruitment and then on individuals' natural attraction to a clear mission of peace-making through health equity. Such a model provides for flexible recruitment of globally diverse experts, though it risks a lack of coordination. Until recently, the PAHS IAB has not enjoyed significant or formal support from any single international institution. However, an increasing number of the international consultants recruited by PAHS to its International Advisory Board are from the University of Alberta in Edmonton, Alberta, Canada (UAlberta). The number of UAlberta Faculty of Medicine and Dentistry members involved in the project has risen to fifteen, providing a critical mass for a coordinated effort to leverage institutional support for this partnership. This paper describes the organic growth of the UAlberta group supporting PAHS, and the ways in which it supports a sister institution in a developing nation.

The role of female hormones on lung function in chronic lung diseases.

BACKGROUND: The prevalence, morbidity, and mortality of inflammatory lung diseases such as asthma, chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF) are increasing in women. There is a dearth of data on the biological mechanisms to explain such observations. However, some large epidemiologic studies suggest that lung function fluctuates during the menstrual cycle in female patients with airways disease but not in women without disease, suggesting that circulating estradiol and progesterone may be involved in this process. DISCUSSION: In asthma, estradiol shuttles adaptive immunity towards the TH2 phenotype while in smokers estrogens may be involved in the generation of toxic intermediate metabolites in the airways of female smokers, which may be relevant in COPD pathogenesis. In CF, estradiol has been demonstrated to up-regulate MUC5B gene in human airway epithelial cells and inhibit chloride secretion in the airways. Progesterone may augment airway inflammation. SUMMARY: Taken together, clinical and in-vivo data have demonstrated a sex-related difference in that females may be more susceptible to the pathogenesis of lung diseases. In this paper, we review the effect of female sex hormones in the context of these inflammatory airway diseases.

Multifaceted intervention to improve diagnosis and treatment of osteoporosis in patients with recent wrist fracture: a randomized controlled trial.

BACKGROUND: Older patients who experience a fragility fracture are at high risk of future fractures but are rarely tested or treated for osteoporosis. We developed a multifaceted intervention directed at older patients with wrist fractures (in the form of telephone-based education) and their physicians (in the form of guidelines endorsed by opinion leaders, supported by reminders) to improve the quality of osteoporosis care. METHODS: In a randomized controlled trial with blinded ascertainment of outcomes, we compared our intervention with usual care (provision of printed educational materials to patients). Eligible patients were those older than 50 years of age who had experienced a wrist fracture and were seen in emergency departments and fracture clinics; we excluded those who were already being treated for osteoporosis. The primary outcome was bisphosphonate treatment within 6 months after the fracture. Secondary outcomes included bone mineral density testing, "appropriate care" (consisting of bone mineral density testing with treatment if bone mass was low) and quality of life. RESULTS: We screened 795 patients for eligibility and randomly assigned 272 to the intervention (137 patients) or control (135 patients) group. The median age was 60 years; 210 (77%) of the subjects were women, and 130 (48%) reported a previous fracture as an adult. Six months after the fracture, 30 (22%) of the intervention patients, as compared with 10 (7%) of the control patients, were receiving bisphosphonate therapy for osteoporosis (adjusted relative risk [RR] 2.6, 95% confidence interval [CI] 1.3-5.1, p = 0.008). Intervention patients were more likely than control patients to undergo bone mineral density testing (71/137 [52%] v. 24/135 [18%]; adjusted RR 2.8, 95% CI 1.9-4.2, p < 0.001) and to receive appropriate care (52/137 [38%] v. 15/135 [11%]; adjusted RR 3.1, 95% CI 1.8-5.3, p < 0.001). There were no differences between the groups in other outcomes. One patient died, and 4 others experienced recurrent fracture. INTERPRETATION: A multifaceted intervention directed at high-risk patients and their physicians substantially increased rates of testing and treatment for osteoporosis. Nevertheless, more than half of the patients in the intervention group were not receiving appropriate care 6 months after their fracture, which suggests that additional strategies should be explored. (ClinicalTrials.gov trial register no. NCT00152321.).