Faculty Bibliography

PURPOSE/OBJECTIVE:To perform a systematic review and meta-analysis of the sensitivity and positive predictive value (PPV) of CT for preoperative parathyroid localization in patients with primary hyperparathyroidism (pHPT), and subsequently compare the different protocols and their performance in different patient groups. MATERIALS AND METHODS/METHODS:We performed a search of the Embase, Pubmed and Cochrane Library databases to identify studies published between January 1, 2000 and March 31, 2016 investigating the diagnostic value of CT for parathyroid localization in patients with biochemical diagnosis of pHPT. Performance of CT was expressed in sensitivity and PPV with pooled proportion using a random-effects model. Factors that could have affected the diagnostic performance were investigated by subgroup analysis. RESULTS:Thirty-four studies evaluating a total of 2563 patients with non-familial pHPT who underwent CT localization and surgical resection were included. Overall pooled sensitivity of CT for localization of the pathological parathyroid(s) to the correct quadrant was 73% (95% CI: 69-78%), which increased to 81% (95% CI: 75-87%) for lateralization to the correct side. Subgroup analysis based on the number of contrast phases showed that adding a second contrast phase raises sensitivity from 71% (95% CI: 61-80%) to 76% (95% CI: 71-87%), and that adding a third phase resulted in a more modest additional increase in performance with a sensitivity of 80% (95% CI: 74-86%). CONCLUSION/CONCLUSIONS:CT performs well in localizing pathological glands in patients with pHPT. A protocol with two contrast phases seems to offer a good balance of acceptable performance with limitation of radiation exposure.

BACKGROUND AND OBJECTIVES/OBJECTIVE:We investigated the rate, stage, and prognosis of thyroid cancer in patients after solid-organ transplantations, and compared this to the general population. METHODS:We performed a retrospective review of patients who developed thyroid cancer after a solid-organ transplantation between January 1988 and December 2013 at a high volume transplant center. Standardized Incidence Ratio's (SIR) were calculated. Additionally, a systematic review of the literature was performed. RESULTS:A total of 10,428 patients underwent solid organ transplantation. Eleven patients (11.4 per 100,000 person-years) developed thyroid cancer: six men and five women with a mean age at diagnosis of thyroid cancer of 58 years. Ten patients underwent surgery and had stage I thyroid cancer. One patient had recurrent disease after a mean follow-up time of 78 months. The SIR varied between 0.75 and 2.3. Seventeen studies were included in the systematic review with a SIR ranging from 2.5 to 35. CONCLUSION/CONCLUSIONS:Rate of thyroid cancer is not significantly higher in patients who underwent solid organ transplantation compared to general population. Stage at presentation and prognosis also appear to be similar to that of the general population. Post-transplant screening for thyroid cancer remains debatable; however, when thyroid cancer is discovered, treatment should be similar to that of non-transplant patients. J. Surg. Oncol. 2017;115:105-108. © 2017 Wiley Periodicals, Inc.

BACKGROUND:The management of low-risk micropapillary thyroid cancer <1 cm in size has come into question, because recent data have shown that nonoperative active surveillance of micropapillary thyroid cancer is a viable alternative to hemithyroidectomy. We conducted a cost-effectiveness analysis to help decide between observation versus operation. METHODS:We constructed Markov models for active surveillance and hemithyroidectomy. The reference case was a 40-year-old patient with recently diagnosed, low-risk micropapillary thyroid cancer. Costs and health utilities were determined using extensive literature review. The willingness-to-pay threshold was set at $100,000/quality-adjusted life year gained. Deterministic and probabilistic sensitivity analyses were performed to account for uncertainty in the model's variables. RESULTS:Active surveillance is dominant (less expensive and more quality-adjusted life years) for a health utility <0.01 below that for disease-free, posthemithyroidectomy state, or for a remaining life expectancy of <2 years. For a utility difference ≥0.02, the incremental cost-effectiveness ratio (the ratio of the difference in costs between active surveillance and hemithyroidectomy divided by the difference in quality-adjusted life years) for hemithyroidectomy is <$100,000/QALY gained and thus cost-effective. For a utility difference of 0.11-the reference case scenario-the incremental cost-effectiveness ratio for hemithyroidectomy is $4,437/quality-adjusted life year gained. CONCLUSION:The cost-effectiveness of hemithyroidectomy is highly dependent on patient disutility associated with active surveillance. In patients who would associate nonoperative management with at least a modest decrement in quality of life, hemithyroidectomy is cost-effective.

BACKGROUND:The recently published 2015 American Thyroid Association guidelines recognize lobectomy as a viable alternative for low-risk cancers and advise more conservative use of radioactive iodine. Some factors indicating adjuvant treatment with radioactive iodine (and therefore completion total thyroidectomy), however, only can be found upon pathologic investigation. METHODS:We performed a retrospective analysis including patients with American Thyroid Association low- and low-to-intermediate risk well-differentiated thyroid cancer 1-4 cm. We evaluated how often radioactive iodine would be indicated and compared this with our historic rate. A subanalysis was performed to determine the rate of completion total thyroidectomy necessary, based on the indications for adjuvant radioactive iodine therapy. RESULTS:A total of 394/1,000 (39.4%) patients were included for final analysis. Adjuvant radioactive iodine would have been favored in 101/394 (25.6%) of patients, which is 2.5 times less than was given in our historic cohort. Completion total thyroidectomy to enable adjuvant radioactive iodine would have been recommended in 29/149 (19.5%) patients preoperatively eligible for lobectomy. CONCLUSION:Despite the tightened regulations for radioactive iodine, about 20% of patients with apparently "low-risk" well-differentiated thyroid cancer who are eligible for lobectomy may need completion total thyroidectomy because of pathologic findings for which radioactive iodine use is listed as considered or favored by the current guidelines.

BACKGROUND:Primary hyperparathyroidism is the most common manifestation of multiple endocrine neoplasia type 1 (MEN1). Guidelines advocate subtotal parathyroidectomy (STP) or total parathyroidectomy with autotransplantation due to high prevalence of multiglandular disease; however, both are associated with a significant risk of permanent hypoparathyroidism. More accurate imaging and use of intraoperative PTH levels may allow a less extensive initial parathyroidectomy (unilateral clearance, removing both parathyroids with cervical thymectomy) in selected MEN1 patients with primary hyperparathyroidism. METHODS:We performed a retrospective cohort study at a high-volume tertiary medical center including patients with MEN1 and primary hyperparathyroidism, who underwent STP or unilateral clearance as their initial surgery from 1995 to 2015. Unilateral clearance was offered to patients who had concordant sestamibi and ultrasound showing a single enlarged parathyroid gland. For both the groups, we compared rates of persistent/recurrent disease and permanent hypoparathyroidism. RESULTS:Eight patients had unilateral clearance and 16 had STP. Subtotal parathyroidectomy patients were younger (37 vs 52 years). One patient in each group had persistent disease. One (13 %) unilateral clearance and five (31 %) STP patients had recurrent hyperparathyroidism after a mean follow-up of 47 and 68 months (p = 0.62). No unilateral clearance patients and two of 16 SPT patients had permanent hypoparathyroidism (p = 0.54). CONCLUSIONS:Some MEN1 patients with primary hyperparathyroidism who have concordant localizing studies may be selected for unilateral clearance as an alternative to STP. For appropriately selected MEN1 patients, unilateral clearance can achieve similar results as STP and has no risk of permanent hypoparathyroidism, and may facilitate possible future reoperations.

BACKGROUND:The reported rate of incidental parathyroidectomy (IP) during thyroid surgery is between 5.2 and 21.6 %. Current literature reports wide discrepancy in incidence, risk factors, and outcomes. Thus study was designed to address definitively the topic of IP and identify associated risk factors and clinical outcomes with this multi-institutional study. METHODS:This retrospective cohort study included 1767 total thyroidectomies that occurred between 1995 and 2014 at two academic centers. Pathologic reports were reviewed for the presence of unintentionally removed parathyroid glands. Demographics, potential risk factors, and postoperative calcium levels were compared with matched control group. Logistic regression, t tests, and Chi squared tests were used when appropriate. RESULTS:IP occurred in 286 (16.2 %) of thyroidectomies. Risk factors for IP were: malignancy, neck dissection, and lymph node metastases (p = 0.005, <0.001, and <0.001). Fifty-three (19.2 %) of IPs were intrathyroidal. Those with IP were more likely to have postoperative biochemical (65.6 vs. 42.0 %; p < 0.001) and symptomatic (13.4 vs. 8.1 %; p = 0.044) hypocalcemia than controls. The number of parathyroids identified intraoperatively was inversely correlated with the number of parathyroid glands in the specimen (p < 0.001). CONCLUSIONS:Our findings indicate that malignancy, lymph node dissection, and metastatic nodal disease are risk factors for IP. Patients with IP were more likely to have postoperative biochemical and symptomatic hypocalcemia than controls, showing that there is a physiologic consequence to IP. Additionally, intraoperative surgeon identification of parathyroid glands results in a lower incidence of IP, highlighting the importance of awareness of parathyroid anatomy during thyroid surgery.

PURPOSE/OBJECTIVE:The great spatial and temporal resolution of positron emission tomography might provide the answer for patients with primary hyperparathyroidism (pHPT) and non-localized parathyroid glands. We performed a systematic review of the evidence regarding all investigated tracers. METHODS:A study was considered eligible when the following criteria were met: (1) adults ≥17 years old with non-familial pHPT, (2) evaluation of at least one PET isotope, and (3) post-surgical and pathological diagnosis as the gold standard. Performance was expressed in sensitivity and PPV. RESULTS:of 51 % (p = 0.01) for all 14 studies. Pooled PPV ranged from 91 to 100 % with a pooled estimate of 98 % (95 % CI 96-100 %). Of the other investigated tracers, 18-FCH seems the most promising with high diagnostic performance. CONCLUSIONS:The results of our meta-analysis show that 11C-MET PET has an overall good sensitivity and PPV and may be considered a reliable second-line imaging modality to enable minimally invasive parathyroidectomy. Our literature review suggests that 18F-FCH PET may produce even greater accuracy and should be further investigated using both low-dose CT and MRI for anatomical correlation.

BACKGROUND:Preoperative imaging in patients with primary hyperparathyroidism and a previous parathyroid operation is essential; however, performance of conventional imaging is poor in this subgroup. Magnetic resonance imaging appears to be a good alternative, though overall evidence remains scarce. We retrospectively investigated the performance of magnetic resonance imaging in patients with and without a previous parathyroid operation, with a separate comparison for dynamic gadolinium-enhanced magnetic resonance imaging. METHODS:All patients undergoing magnetic resonance imaging prior to parathyroidectomy for primary hyperparathyroidism (first time or recurrent) between January 2000 and August 2015 at a high-volume, tertiary care, referral center for endocrine operations were included. We compared the sensitivity and positive predictive value of magnetic resonance imaging with conventional ultrasound and sestamibi on a per-lesion level. RESULTS:A total of 3,450 patients underwent parathyroidectomy, of which 84 patients with recurrent (n = 10) or persistent (n = 74) disease and 41 patients with a primary operation were included. Magnetic resonance imaging had a sensitivity and positive predictive value of 79.9% and 84.7%, respectively, and performance was good in both patients with and without a previous parathyroid operation. Adding magnetic resonance imaging to the combination of ultrasound and sestamibi resulted in a significant increase in sensitivity from 75.2% to 91.5%. Dynamic magnetic resonance imaging produced excellent results in the reoperative group, with sensitivity and a positive predictive value of 90.1%. CONCLUSION:Technologic advances have enabled faster and more accurate magnetic resonance imaging protocols, making magnetic resonance imaging an excellent alternative modality without associated ionizing radiation. Our study shows that the sensitivity of multimodality imaging for parathyroid adenomas improved significantly with the use of conventional and dynamic magnetic resonance imaging, even in the case of recurrent or persistent disease.

BACKGROUND:The extent of thyroidectomy for low-risk well-differentiated thyroid cancer (WDTC) remains controversial. Historically, total thyroidectomy (TT) has been recommended for WDTC ≥1 cm in size. However, recent National Comprehensive Cancer Network and American Thyroid Association guidelines recognize unilateral thyroid lobectomy as a viable alternative for 1-4 cm cancers due to their otherwise favorable prognosis, with TT remaining the preferred option for tumors with unfavorable pathological characteristics. This study sought to determine how often a completion TT would be recommended based on these guidelines if lobectomy was initially performed in patients with 1-4 cm WDTC without preoperatively known risk factors. METHODS:Patients who underwent thyroidectomy for 1-4 cm WDTC (January 2000 to January 2010) were retrospectively reviewed. Patients with preoperatively known high-risk characteristics, including gross extrathyroidal extension (ETE) on preoperative imaging, clinically apparent lymph node metastases, distant metastases, history of radiation, and positive family history, were excluded. The pathology specimens from the cancer-containing lobe were evaluated for features that would lead to a recommendation for TT based on current guidelines, including aggressive histology, vascular invasion, microscopic ETE, positive margins, and any positive lymph nodes within the specimen. RESULTS:Of 1000 consecutive patients operated for WDTC, 287 would have been eligible for lobectomy as the initial operation. The mean age in this cohort was 45 years, and 80% were women. Aggressive tall-cell variant histology was found in one patient (0.5%), angio-invasion in 34 (12%), ETE in 48 (17%), positive margins in 51 (18%), and positive lymph nodes in 49 (18%) patients. Completion TT would have been recommended in 122/287 (43%) patients. Even in those with 1-2 cm cancers, completion TT would have been recommended in 52/143 (36%) patients. CONCLUSIONS:Nearly half of the patients with 1-4 cm WDTC who are eligible for lobectomy under current guidelines would require completion TT based on pathological characteristics of the initial lobe. Surgeons, endocrinologists, and patients need to balance the relative benefits, risks, and costs of initial TT versus the possible need for reoperative completion TT.

BACKGROUND:Incomplete surgical resection with gross positive tumor margin increases the risk of recurrence in patients with well-differentiated thyroid cancer (WDTC); however, it is not clear whether a microscopic positive margin found only on final pathology has similar implications on patient outcomes. METHODS:We conducted a single-institution retrospective review of all patients undergoing total thyroidectomy for T1-T2 WDTC (January 2000-January 2010). Factors that may influence the risk of locoregional recurrence or distant metastasis were evaluated by univariate and multivariate analysis. RESULTS:Of 1000 consecutive patients undergoing surgical resection for WDTC, 684 T1-T2 cancers were included. Mean age was 46 years and 81 % were women. Of this total cohort, 78 (11 %) patients had microscopic positive margins. Radioactive iodine (RAI) was administered in 47/78 (60 %) patients with positive margins versus 312/606 (51 %) patients without positive margins. After a mean follow-up of 46 months, 53 (8 %) patients developed recurrent disease (1 local and 52 nodal). On multivariate analysis, nodal metastases (N1, odds ratio [OR] 7.7) and contralateral multifocality (OR 3.7) were independent risk factors for recurrent disease. A microscopic positive margin was not a risk factor for recurrence. CONCLUSIONS:A microscopic positive margin found only on final pathological analysis does not increase the risk of recurrence in T1-T2 WDTC. Clinicians should interpret such pathology findings accordingly when considering further surveillance and treatment decisions such as the use of RAI ablation.