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Background. Intraoperative identification of parathyroid adenomas can be challenging. We hypothesized that low-doses methyl- ene blue (MB) and near-infrared fluorescence (NIRF) imaging could be used to identify parathyroid adenomas intraoperatively. Methods. MB was injected intravenously after exploration at a dose of 0.5 mg/kg into 12 patients who underwent parathyroid surgery. NIRF imaging was performed using the Mini-FLARE imaging system. Results. In 10 of 12 patients, histology confirmed a parathyroid ade- noma. In 9 of these patients, NIRF could clearly identify the parathyroid adenoma during surgery. Seven of these 9 patients had a positive preoperative 99m Tc-sestamibi single photon emission CT (SPECT) scan. Importantly, in 2 patients, parathyroid adenomas could be identified only using NIRF. Conclusion. This is the first study to show that low-dose MB can be used as NIRF tracer for identification of parathyroid adenomas, and suggests a correlation with preoperative 99m Tc-sestamibi SPECT scan- ning. V C 2013 Wiley Periodicals, Inc. Head Neck 36: 853-858, 2014

Summary Objective Lithium has been reported to increase radioactive iodine (RaI) doses in benign thyroid disease and in differentiated thyroid carcinoma (DTC). It is not known whether lithium influences the outcome of RaI therapy in DTC. We therefore studied the clinical effects of RaI without and with lithium carbonate in patients with proven metastatic DTC. Controversy also exists on the mechanism by which lithium increases RaI dose in DTC. We performed an in vitro study specifically aimed at examining the effects of lithium on the sodium iodide symporter (NIS). Design In a clinical study, 12 patients were selected with metastases of DTC who had received previous RaI therapy without lithium (control) that had not influenced tumour progression, despite RaI accumulation in metastases. The patients received 1200 mg lithium carbonate/day followed by 6000 MBq RaI. Outcome parameters were RaI uptake, serum thyroglobulin (Tg) levels and radiological dimensions of metastases compared between RaI with lithium and control. In an in vitro study, iodide uptake was studied in the benign rat thyroid cell line FRTL-5, in the polarized non-thyroid MDCK cell line, stably transfected with human sodium iodide symporter (hNIS) to study the effects of lithium on NIS in a non-thyroid background, and the human follicular thyroid carcinoma cell line FTC133-hNIS to study lithium effects in a background of DTC. Lithium chloride (LiCl) was added in concentrations up to 2 mm for 0–48 h. Both steady-state iodide uptake (30 min) and initial rate (2 min) were studied using a specific activity of 100 mCi/mmol I, the latter experiment to determine lithium effects on substrate dependency. Iodide efflux studies were performed as well. Results Despite an increased uptake of RaI in seven patients, no beneficial effect of RaI with lithium was observed on the clinical course as assessed by serum Tg measurements and radiographically. In the in vitro studies, no effects of LiCl on iodide uptake or efflux were observed. Conclusions The addition of lithium to RaI did not have any beneficial effects on the clinical course in 12 patients with metastatic DTC. No beneficial effects of lithium on iodide uptake were observed in vitro. Therefore, the clinical value of lithium in DTC remains subject to debate.

Summary objective To investigate to what extent thyroid remnant ablation and withdrawal from thyroxine are required to achieve sufficient accuracy of serum thyroglobulin (Tg) measurements as an indicator of tumour recurrence in the follow-up of patients with differentiated thyroid carcinoma. design and methods We conducted a meta-analysis of the literature from 1975 to 2003 on serum Tg measurements in the follow-up of differentiated thyroid carcinoma. In a computer-based search, we initially found 915 articles that were finally narrowed down to 120. These 120 papers were subjected to strict in/and exclusion criteria, leaving 46 articles (totalling 9094 patients). Data from these articles were extracted in a structured fashion and were grouped according to initial therapy, TSH status, Tg assay method and definition of a ‘gold standard’. Original 2 × 2 tables were pooled by summary receiver operating characteristic curve analysis (sROCa), best estimates of sensitivity and specificity being obtained by the combination of sROCa and Mantel–Haenszel odds ratios. results Despite considerable differences between series in laboratory and clinical methodology, we consistently found higher specificity for Tg measurements after thyroid remnant ablation than after surgery alone. Highest pooled sensitivity 0·961 ± 0·013 (SE) was found for immunometric assay (IMA) after thyroid remnant ablation and thyroid hormone withdrawal, at a specificity of 0·947 ± 0·007. Pooled sensitivity decreased significantly if ablated patients were tested while on thyroid hormone (0·778 ± 0·023, at a specificity of 0·977 ± 0·005). Significantly decreased pooled specificity was found in patients who did not undergo remnant ablation (sensitivity 0·972 ± 0·023, at a specificity of 0·759 ± 0·028). If recombinant human TSH (rhTSH) stimulation was used as a substitute for thyroxine withdrawal, sensitivity remained high (0·925 ± 0·018) while specificity decreased to 0·880 ± 0·013. In all analyses, specificity of Tg would decrease when unspecified activity in the thyroid region at scintigraphy was considered benign, whereas sensitivity decreased when such activity was considered malignant. conclusion This study confirms that the best accuracy of Tg-guided follow-up in patients treated for differentiated thyroid carcinoma is obtained if treatment includes remnant ablation, and Tg testing is performed while off thyroxine.

Summary BACKGROUND The preferred treatment of Cushing's disease (CD) nowadays is transsphenoidal pituitary surgery (TPS). Prior to TPS, patients at the Leiden University Medical Centre were treated by unilateral adrenalectomy followed by external pituitary irradiation (UAPI). We report on long-term results of both UAPl and TPS and compare remission, relapse rates, and complications. PATIENTS AND METHODS A retrospective Study was carried out on 130 patients with CD. Patients with pituitary macroadenoma were excluded. Eighty-six and 44 patients underwent UAPl and TPS, respectively. Of these patients, 85 and 41 were evaluable for long-term results. RESULTS Remission following UAPl and TPS was identical at 64% (54/85 and 27/41). Cumulative relapse was also comparable - 17% (9/54) and 22% (6/27), respectively, - for UAPl and TPS, although the mean follow-up periods were different - 21.4 years and 8.5 years, respectively. Cumulative disease-free survival curves after UAPl and TPS are identical until 5 years of follow-up, but diverge thereafter indicating more sustained remissions following UAPl (P=0.17, Wilcoxon statistic). Pituitary dysfunction following UAPl (36%) and pituitary surgery (55%) likewise did not dlffer significantly. However, pituitary dysfunction was an immediate event after TPS, whereas it developed after a mean interval of 17.8 years following UAPI. Low-dose dexamethasone testing during follow-up had no value in predicting therapeutic outcome. CONCLUSIONS The results of unilateral adrenalectomy followed by external pituitary irradiation do not Justify that this therapy is totally abandoned in favour of transsphenoidal pituitary surgery. Unilateral adrenalectorny followed by external pituitary irradiation is a valid therapeutic modality for the treatment of Cushing's disease, and could be considered as alternative to bilateral adrenalectomy and under some circumstances to transsphenoidal pituitary surgery.

The use of carcinoembryonic antigen (CEA) to monitor patients after intentionally curative colon cancer resection can have advantages (improved life expectancy as a result of early detection of recurrences) as well as disadvantages (false-positive CEA rises and early detection of incurable recurrences in asymptomatic patients). This study estimated how the favorable and unfavorable effects of CEA monitoring affect life expectancy and quality of life of colon cancer patients. These effects were simulated using a Markov analysis for which the variables had been defined on the basis of data found in literature. The influence of CEA monitoring on quality adjusted life expectancy appears to be modest and varies, according to the data used, from an average increase of +7 days (+0.3%) to an average decrease of -5 days (-0.09%). This value is dependent, among other things, on patient related variables; the adverse effects especially dominate in older patients with a favorable Dukes' stage of the primary tumor and if operative mortality exceeds 2%. The total cost of CEA monitoring, including diagnosis and therapy performed as a result of true- or false-positive CEA rise, is considerable. High cost and low return leads to a high marginal cost-effectiveness ratio, which varies from $22,963 to $4,888,208 per quality adjusted life year saved. It is concluded that CEA monitoring should not be used for routine following of colon cancer patients, as its advantages have so far been demonstrated insufficiently.