Biomedical subjects
Publications and source records attributed to Clive Harmer.
We report a case of malignant pleural mesothelioma with histologically proven spontaneous regression of pleural disease. During a 12-year follow-up there was a single recurrence, which was a lesion in the chest wall at 6 years that was surgically excised. A prominent host response to tumor was seen in both the primary tumor and the recurrence.
CONTEXT: Radioiodine ablation of the thyroid remnant after thyroidectomy is commonly performed in the management of patients with differentiated thyroid cancer. Although many centers administer an activity of 100 mCi, there is uncertainty over using a lower activity. OBJECTIVE: A systematic review of the published literature was used to compare the success rates of remnant ablation using approximately 30 mCi with approximately 100 mCi (1.1 vs. 3.7 GBq). DATA SOURCES: Data were obtained from MEDLINE and EMBASE for the years 1966 to March 2006. STUDY SELECTION: All studies that reported rates of successful ablation associated with approximately 30 or approximately 100 mCi of radioiodine were reviewed. DATA EXTRACTION: Studies were based on reviews of patient case notes (n = 41), prospective cohorts (n = 12), and randomized trials (n = 6). We obtained the success of thyroid remnant ablation according to different administered activities of radioiodine. Where a study reported on two or more activities, the risk ratio of having a successful ablation (approximately 30 vs. approximately 100 mCi) was calculated and combined in a meta-analysis. DATA SYNTHESIS: Observational studies confirmed the high ablation success rate ( approximately 80%) using approximately 100 mCi, although 22% of studies reported a rate of 90% or greater. The pooled ablation success rate in these studies was 10% lower using 30 mCi compared with 100 mCi (95% confidence interval, 3-17%; P = 0.01). The meta-analysis of the randomized trials produced equivocal results. For example, the rate of successful ablation in patients given 30 mCi was 8% lower compared with 100 mCi (95% confidence interval, 29% lower or up to 20% greater, P = 0.58), consistent with there being no difference or that 30 mCi is much less effective. CONCLUSIONS: From the published data, it is not possible to reliably determine whether ablation success rates using 30 mCi are similar to using 100 mCi. Large randomized trials are needed to resolve the issue and guide clinical practice.
An 80-year-old woman was referred for a painless mass arising in right side of her neck of 4 months' duration. Ultrasound revealed a multinodular goiter, but cytology confirmed a follicular carcinoma. Thyroid function was normal. Total thyroidectomy was performed with evidence of tumor infiltration into the strap muscles extending up to the right submandibular gland and right internal jugular vein, which was completely occluded. Radioiodine was considered as the treatment of choice postoperatively. This is an unusual case of SVC obstruction caused by tumor embolus diagnosed on I-131 scan.
OBJECTIVE: To determine, based on published literature and expert clinical experience, current indications for the post-surgical administration of a large radioiodine activity in patients with differentiated thyroid cancer. DESIGN AND METHODS: A literature review was performed and was then analyzed and discussed by a panel of experts from 13 European countries. RESULTS: There is general agreement that patients with unifocal microcarcinomas = 1 cm in diameter and no node or distant metastases have a <2% recurrence rate after surgery alone, and that post-surgical radioiodine confers recurrence and cause-specific survival benefits in patients, strongly suspected of having persistent disease or known to have tumor in the neck or distant sites. In other patients, there is limited evidence that after complete thyroidectomy and adequate lymph node dissection performed by an expert surgeon, post-surgical radioiodine provides clear benefit. When there is any uncertainty about the completeness of surgery, evidence suggests that radioiodine can reduce recurrences and possibly mortality. CONCLUSION: This survey confirms that post-surgical radioiodine should be used selectively. The modality is definitely indicated in patients with distant metastases, incomplete tumor resection, or complete tumor resection but high risk of recurrence and mortality. Probable indications include patients with tumors >1 cm and with suboptimal surgery (less than total thyroidectomy or no lymph node dissection), with age <16 years, or with unfavorable histology.
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OBJECTIVE: To assess the value of the diagnostic whole body (131)I scan after thyroidectomy and (131)I ablation. DESIGN: Retrospective analysis of all patients with differentiated thyroid cancer treated in one centre between 1990 and 2000. RESULTS: A total of 153 consecutive patients who underwent diagnostic scanning following ablative therapy were identified. This diagnostic scan was positive in 20 patients (13%) and faintly positive in 16 patients (11%). The majority (117 patients) had negative scans. Of the 20 patients with positive scans, four received no further treatment, nine showed no abnormal uptake following a second ablative (131)I dose and seven had uptake in the thyroid bed (six) or in neck nodes (one) after repeat ablation. OUTCOME: In the group with positive scans, the four patients who received no further treatment and the nine with a negative second ablation scan remained disease free during follow-up. No patient with a positive diagnostic scan received additional (131)I therapy which would not otherwise have been given based on the clinical findings, serum thyroglobulin (Tg) values or the presence of anti-Tg antibodies. Ten of the patients with negative scans developed recurrent disease which was always detected clinically or by a rising serum Tg value. CONCLUSIONS: Diagnostic whole body (131)I scans add little extra information and in our experience do not influence patient management. They should be reserved for patients in whom serum Tg levels are unreliable because of the presence of antibodies or when there is clinical suspicion of tumour.
Benign thyroid disorders are strong risk factors for non-medullary thyroid cancer (NMTC). Germline variation in Tg (thyroglobulin) and TSHR (thyroid stimulating hormone receptor) confers an increased risk of benign thyroid disorders. To explore the hypothesis that polymorphic variation in these genes affects the risk of NMTC we compared the frequency of TgQ2511R, TSHR-P52T and TSHR-D727E genotypes in two series of NMTC cases and controls (group 1, Canadian 102 cases and 102 controls; group 2, British 202 cases and 298 controls). No significant association was seen with TSHR-P52T and TSHR-D727E genotypes and risk of NMTC. However, the frequency of the R-allele of TgQ2511R was over represented in NMTC cases in both study populations. The odds ratios associated with hetero- and homozygosity for the R-allele were 1.6 (95% confidence interval, 1.1-2.5) and 2.0 (95% confidence interval, 1.2-3.3), respectively. Although the risk of NMTC associated with the TgQ2511R R-allele is modest, its high prevalence in the general population suggests it may make a significant contribution to the incidence of NMTC.
BACKGROUND: The authors assessed the biologic behavior of differentiated thyroid carcinoma in patients age 70 years or older and evaluated factors that influenced long-term survival. METHODS: Among 1448 patients with differentiated thyroid carcinoma who were treated at the authors' institution over the past 60 years, 111 patients were identified who were age 70 years or older at the time of their initial diagnosis (range, 70-93 years). The authors conducted a retrospective analysis of the outcome of these 111 patients, who had a median follow-up of 9 years (range, 2-9 years). RESULTS: There were 83 female patients and 28 male patients (female to male ratio, 3:1). Fifty-eight tumors were papillary, 46 tumors were follicular, and 7 tumors were Hürthle cell carcinoma. Eighty percent of patients presented with a thyroid mass, and 70% of tumors were pathologic stage T3 (pT3) or pT4. Lymph node disease was evident at presentation in 44% of patients, and distant metastases were documented at diagnosis in 23% of patients. Forty-six patients underwent total thyroidectomy, and the remaining patients underwent subtotal thyroidectomy or biopsy only. Radioiodine was administered to 80 patients, and external beam radiotherapy was administered to 19 patients. The cause specific survival rates were 75%, 50%, and 50% at 5 years, 10 years, and 15 years, respectively. Multivariate analysis showed that the presence of metastases was the most important independent prognostic factor for survival. External beam radiotherapy was associated with a poorer prognosis, in that it was reserved for patients with either inoperable disease or residual disease after surgery and patients with no uptake of radioiodine. CONCLUSIONS: A large proportion of thyroid tumors showed extrathyroid spread and distant metastases, which frequently were not iodine-avid. The prevalent histologic type was papillary, often with features of poor differentiation. Thyroid carcinoma in the elderly appears to behave more aggressively, and they have a less favorable prognosis compared with younger adults.
Thyroid cancers are a diverse group of malignant disorders ranging from indolent micropapillary carcinoma, which has no effect on life expectancy, to anaplastic tumours, which are invariably fatal even with aggressive treatment. Although the estimated incidence has increased by 14.6% over the past 40 years, the estimated death rate has fallen by 21%, probably as a result of earlier diagnosis. The natural history of thyroid tumours is no longer a mystery, and the prognostic factors identified can predict outcome fairly accurately. Improvements in management have mostly depended on information from large retrospective series, though there are still many areas open to debate. There has been, however, a general acceptance that thyroid cancer should be managed by multidisciplinary teams in specialised units following evidence-based guidelines.
OBJECTIVE: Young adults with differentiated thyroid cancer are treated with high doses of radioiodine and have an excellent long-term prognosis. However, there is limited information on the effects of this treatment on the gonads and fertility in male patients. We have reviewed the outcome of treatment in our centre with respect to male fertility. We have also assessed directly the radiation dose received by the testes. DESIGN: Retrospective analysis of males attending the thyroid clinic at the Royal Marsden Hospital for treatment of differentiated thyroid cancer. A prospective study was also performed to assess radiation dose to testes in 14 consecutive patients attending for thyroid cancer treatment. PATIENTS: Males under the age of 40 years at the time of treatment with a minimum of 3 years follow-up. MEASUREMENTS: Number of children fathered by patients and number of congenital malformations. For the prospective study: gonadal function assessed by serum FSH, LH and testosterone measurements; radiation dose to the testes (Gy) measured by thermoluminescent dosimetry. RESULTS: Fertility was assessed in 122 men with a median follow-up of 21 years (range 3-39) of whom 93 were under active follow-up. One hundred and six children were fathered by 59 patients; the remainder had no wish to have children. No major malformations were reported. Of these 59 patients, 12 had received a single 3 GBq ablation dose, 19 had been treated with up to 14 GBq radioiodine and 28 had received up to 44 GBq. In 14 patients followed prospectively, the median estimated radiation dose to each testis was 6.4 cGy following 3 GBq, 14.1 cGy following 5.5 GBq and 21.2 cGy following 9.2 GBq. There was a transient elevation in serum FSH after radioiodine which normalized within 9 months from the last administration. CONCLUSIONS: Radioiodine treatment for thyroid cancer may result in transient impairment of gonadal function. The radiation dose absorbed by the testis after a single ablative dose of radioiodine is well below that associated with permanent damage to germinal epithelium and the risk of infertility in these patients is minimal. Patients requiring multiple administrations for persistent or metastatic thyroid cancer may be at greater risk of gonadal damage although even in this group, we found no evidence of infertility.