Calcitonin testing for detection of medullary thyroid cancer in people with thyroid nodules.

BACKGROUND: Thyroid nodules are very common in general medical practice, but rarely turn out to be a medullary thyroid carcinoma (MTC). Calcitonin is a sensitive tumour marker for the detection of MTC (basal calcitonin). Sometimes a stimulation test is used to improve specificity (stimulated calcitonin). Although the European Thyroid Association's guideline advocates calcitonin determination in people with thyroid nodules, the role of routine calcitonin testing in individuals with thyroid nodules is still questionable. OBJECTIVES: The objective of this review was to determine the diagnostic accuracy of basal and/or stimulated calcitonin as a triage or add-on test for detection of MTC in people with thyroid nodules. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase and Web of Science from inception to June 2018. SELECTION CRITERIA: We included all retrospective and prospective cohort studies in which all participants with thyroid nodules had undergone determination of basal calcitonin levels (and stimulated calcitonin, if performed). DATA COLLECTION AND ANALYSIS: Two review authors independently scanned all retrieved records. We extracted data using a standard data extraction form. We assessed risk of bias and applicability using the QUADAS-2 tool. Using the hierarchical summary receiver operating characteristic (HSROC) model, we estimated summary curves across different thresholds and also obtained summary estimates of sensitivity and specificity at a common threshold when possible. MAIN RESULTS: In 16 studies, we identified 72,368 participants with nodular thyroid disease in whom routinely calcitonin testing was performed. All included studies performed the calcitonin test as a triage test. Median prevalence of MTC was 0.32%. Sensitivity in these studies ranged between 83% and 100% and specificity ranged between 94% and 100%. An important limitation in 15 of the 16 studies (94%) was the absence of adequate reference standards and follow-up in calcitonin-negative participants. This resulted in a high risk of bias with regard to flow and timing in the methodological quality assessment. At the median specificity of 96.6% from the included studies, the estimated sensitivity (95% confidence interval (CI)) from the summary curve was 99.7% ( 68.8% to 100%). For the median prevalence of MTC of 0.23%, the positive predictive value (PPV) for basal calcitonin testing at a threshold of 10 pg/mL was 7.7% (4.9% to 12.1%). Summary estimates of sensitivity and specificity for the threshold of 10 pg/mL of basal calcitonin testing was 100% (95% CI 99.7 to 100) and 97.2% (95% CI 95.9 to 98.6), respectively. For combined basal and stimulated calcitonin testing, sensitivity ranged between 82% and 100% with specificity between 99% and 100%. The median specificity was 99.8% with an estimated sensitivity of 98.8% (95% CI 65.8 to 100) . AUTHORS' CONCLUSIONS: Both basal and combined basal and stimulated calcitonin testing have a high sensitivity and specificity. However, this may be an overestimation due to high risk of bias in the use and choice of reference standard The value of routine testing in patients with thyroid nodules remains questionable, due to the low prevalence, which results in a low PPV of basal calcitonin testing. Whether routine calcitonin testing improves prognosis in MTC patients remains unclear.

Patients' perception of diagnostic tests in the preoperative assessment of esophageal cancer.

OBJECTIVE: Defining an optimal staging strategy requires an evaluation of the effectiveness and costs of diagnostic tests and may include the burden of these tests for patients. This study evaluated the burden of cervical ultrasonography (US), endoscopic ultrasonography (EUS), computed tomography (CT) and positron emission tomography (PET) in patients with esophageal carcinoma (EC). METHODS: Consenting consecutive patients underwent a standard preoperative work-up. Burden of testing was evaluated with a self-report questionnaire addressing anxiety, embarrassment, and discomfort, each measured on a 1(none) to 5 (extreme) point-scale. An overall burden score was calculated by summing the three item scores. In addition, patients were asked to rank the four tests from least to most inconvenient. Statistical analysis was performed with nonparametric tests. RESULTS: 82 patients (67 , 15 ; mean age 64.3 yrs) participated. For most tests and most dimensions of burden, the large majority of subjects was in categories 1 and 2.With respect to anxiety, the rank order (from highest burden to lowest burden) was EUS, US, PET, and CT (average scores 1.7, 1.5, 1.4, and 1.2, respectively). For embarrassment, the rank order was EUS, PET, US, and CT (1.9, 1.5, 1.4, and 1.3 respectively). For discomfort, the rank order was EUS, PET, US and CT (2.0, 1.6, 1.4, and 1.2, respectively). And for total burden, the rank order was EUS, PET, US and CT (5.6, 4.6, 4.2, and 3.7). PET was ranked as least inconvenient by 35% of patients and as most inconvenient by 16% compared with the other tests. CONCLUSION: Significant but small differences were observed in patient burden for imaging tests to evaluate EC. The perceived burden of PET was lower than that of EUS, but higher than the burden of CT. However absolute values were low for all tests and therefore patient burden will not be a key feature for the construction of an optimal staging algorithm for EC.

An introduction to managing medullary thyroid cancer.

MTC is a rare neuroendocrine thyroid tumour accounting for 3% to 10% of all thyroid malignancies. It can occur in a sporadic and a hereditary clinical setting. Hereditary MTC may either occur alone (familial MTC, FMTC) or as part of multiple endocrine neoplasia (MEN) type 2A, or MEN 2B. These disorders are due to germline mutations in the RET (REarranged during Transfection) gene. In carriers of MEN 2B-associated RET mutations, prophylactic thyroidectomy is indicated before the first year of life. In the case of MEN 2A-associated germline RET mutations with a high-risk profile, total thyroidectomy is warranted before the age of 2 years and certainly before the age of 4 years. At that age the risk of invasive MTC and metastases is acceptably low. Depending on the type of RET mutation, thyroidectomy can take place at an older age in patients with a lower risk profile. In case of elevated basal or stimulated serum calcitonin, preventive surgery including total thyroidectomy and central compartment dissection should be performed regardless of age. When MTC presents as a palpable tumour, total thyroidectomy should be combined with extensive lymph node dissection of levels II-V on both sides and level VI to prevent locoregional recurrences.