John I. Lew

Pediatric Thyroid Carcinoma: Incidence and Outcomes in 1753 Patients

OBJECTIVE To examine outcomes and predictors of survival for pediatric patients with thyroid carcinoma. METHODS The Surveillance, Epidemiology, and End Results (SEER) registry from 1973 to 2004 was queried for all patients with thyroid carcinoma less than 20 y of age. RESULTS A total of 1753 patients with malignant thyroid neoplasms were identified with an age-adjusted annual incidence of 0.54 cases per 100,000 persons. There has been a significant increase in the annual incidence by 1.1% per y. Female patients outnumbered males 4 to 1. Tumors were classified as papillary (n=1044, 60%), follicular variant of papillary (n=389, 23%), follicular (n=165, 10%), and medullary (n=87, 5%). The majority of patients presented with localized and regional disease. Overall mean survival time (MST) was 30.5 y. The MST for females was 40 y, whereas males survived an average of 20.4 y (P=0.0001). Patients with medullary cancer had significantly shorter mean survival than those with papillary cancer (P=0.006). Surgical treatment significantly improved outcome. Multivariate analysis demonstrated that male gender, nonpapillary histology, distant disease, and no surgery were all independent prognostic factors of worse outcome. For patients with medullary thyroid carcinoma, radiation therapy was also identified as an independent predictor of lower survival. CONCLUSION The incidence of pediatric thyroid cancer is increasing. Females have a higher incidence than males, but enjoy longer survival. Papillary thyroid cancer has overall excellent survival. Male gender, nonpapillary tumor, distant metastases, and nonsurgical treatment all predict worse outcome.

Surgical management of primary hyperparathyroidism: state of the art.

This article reviews the current state of the art regarding therapy for primary hyperparathyroidism. Clinical evaluation and indications for parathyroidectomy are described, followed by a review of surgical techniques currently being practiced and possible outcomes involved. Focused parathyroidectomy has become a successful alternative to conventional bilateral cervical exploration.

Fine Needle Aspiration of the Thyroid: Correlation with Final Histopathology in a Surgical Series of 797 Patients

BACKGROUND Fine needle aspiration (FNA) is accepted as the diagnostic procedure of choice in the management of patients with thyroid nodules. Follicular/Hürthle cell neoplasms have traditionally been grouped under the category of indeterminate FNA results. This study examined the experience with FNA in a large cohort of patients undergoing thyroidectomy before adoption of the Bethesda system for reporting thyroid cytopathology (BSTC) at a single academic medical center. STUDY DESIGN A retrospective review of prospectively collected data of 797 consecutive patients with dominant nodules >1 cm who underwent FNA and thyroidectomy from 2003 to 2009 was performed. Patients were categorized into groups based on FNA results: malignant, benign, indeterminate, and nondiagnostic. The indeterminate group had FNA results that included follicular neoplasm, Hürthle cell neoplasm, and suspicion of papillary thyroid cancer. FNA results were compared with final histopathology after thyroidectomy. RESULTS FNA results included 147 (18%) positive for malignancy, 255 (32%) benign, 358 (45%) indeterminate, and 37 (5%) nondiagnostic. The overall malignancy rate on final histopathology was 369 of 797 (46%). Overall, there was a false positive rate of 2% and false negative rate of 8.6%. Among the 358 indeterminate FNA results, carcinoma was found in 81 (36%) of 223 follicular neoplasms, 18 (36%) of 50 Hürthle cell neoplasms, and 78 (92%) of 85 that were suspicious for papillary thyroid cancer. When FNA was nondiagnostic, cancer was present in 9 of 37 (24%). Among 39 patients with benign FNA who had cancer on final histopathology, 22 of 255 (8.6%) had cancer in the index thyroid nodule, and 81% of cancers were >1 cm. CONCLUSIONS Patients with FNA and dominant nodules >1 cm, who underwent thyroidectomy, had an overall rate of thyroid malignancy of 46%. There was a cancer prevalence of 8.6% in patients with benign FNA results referred for surgical resection. Despite not yet implementing the BSTC at this medical center, the majority of thyroidectomies were adequately performed for indeterminate FNAs with underlying malignancy.

Role of intraoperative parathormone monitoring during parathyroidectomy in patients with discordant localization studies

BACKGROUND Many patients with sporadic primary hyperparathyroidism (SPHPT) have discordant preoperative Tc-99m-sestamibi (MIBI) and ultrasonography studies prior to focused parathyroidectomy (PTX). This study examines the usefulness of intraoperative parathormone monitoring (IPM) during PTX in patients with discordant preoperative localization studies. METHODS A retrospective series of 225 consecutive SPHPT patients with MIBI scans and surgeon performed ultrasonography (SUS) prior to focused parathyroidectomy were studied. All patient operations were reviewed, and how IPM changed operative management was determined. Correct gland localization, presence of multigland disease (MGD), and operative outcome were also examined. RESULTS In 225 patients, overall operative success was 97%, and IPM changed operative management in 29% of patients. In 85 patients (38%) with discordant studies, operative success was 93%; IPM changed operative management in 74% of these patients. IPM allowed for 66% (56/85) of these operations to be performed as unilateral neck exploration and confirmed removal of abnormal glands in 7 patients with MGD. In 140 patients (62%) with concordant localization, in which operative success was 99%, IPM changed operative management in only 2% (3/140) of these patients with MGD. CONCLUSION Although of marginal benefit in patients with concordant imaging studies, IPM remains essential for performing successful PTX with discordant or incorrect concordant localization.

Focused parathyroidectomy guided by intra-operative parathormone monitoring does not miss multiglandular disease in patients with sporadic primary hyperparathyroidism: A 10-year outcome

BACKGROUND There remains concern that focused parathyroidectomy guided by intra-operative parathormone monitoring (IPM) will miss multiglandular disease (MGD) leading to a higher recurrence rate. This study reports the 10-year outcome of patients with sporadic primary hyperparathyroidism treated by focused parathyroidectomy guided by IPM. METHODS From 1993 to 1998, 173 consecutive patients with sporadic primary hyperparathyroidism underwent focused parathyroidectomy guided by IPM. When IPM showed >50% decrease 10 minutes after abnormal gland excision, the operation was completed. Recurrent hyperparathyroidism was defined as elevated serum calcium and parathormone (PTH) levels >6 months after successful parathyroidectomy. RESULTS There were 164 patients with a mean follow-up of 83 months. In this group, 96% patients had single gland disease (SGD) and 4% had MGD. Five (3%) patients developed recurrent hyperparathyroidism at 2, 4, 9, 10, and 12 years. In 43 eucalcemic patients followed for >10 years, PTH levels remained normal in 54%, were constantly above normal range in 2%, or varied between normal and above normal range in 44%. CONCLUSION In patients 10 years after treatment, IPM-guided parathyroidectomy does not fail to identify MGD, allows for limited dissection in SGD, and shows that various sized parathyroid glands left in situ do not cause higher recurrence rates.

Long-term outcome of patients with elevated parathyroid hormone levels after successful parathyroidectomy for sporadic primary hyperparathyroidism.

HYPOTHESIS Untreated long-term elevated parathyroid hormone (PTH) levels after successful parathyroidectomy may predict recurrent hyperparathyroidism (HPT). Although elevated PTH levels have been reported in eucalcemic patients after parathyroidectomy for sporadic primary HPT, the long-term clinical significance of this finding remains unclear. DESIGN Retrospective case series. SETTING Tertiary referral center. PATIENTS Five hundred seventy-six consecutive patients with HPT. INTERVENTION Parathyroidectomy guided by intraoperative monitoring of PTH levels. MAIN OUTCOME MEASURES Overall incidence of elevated PTH levels (measurements of >or= 70 pg/mL at any time during follow-up) and recurrent HPT (hypercalcemia and elevated PTH levels more than 6 months after parathyroidectomy). RESULTS Of the 505 patients who underwent successful parathyroidectomy in this series and were followed up for more than 6 months, 337 (66.7%) consistently had PTH levels within the reference range, and 168 (33.3%) had elevated PTH levels. Of the 168 patients with elevated PTH levels, only 8 (4.8%) developed recurrent disease. The earliest recurrence occurred 2 years postoperatively. Factors associated with elevated PTH levels included advanced age, higher preoperative PTH levels, and mild postoperative renal insufficiency. CONCLUSION Although one-third of the patients had elevated PTH levels after successful parathyroidectomy, most of these patients with elevated PTH levels (95%) will achieve long-term eucalcemia.

Operative Failure in the Era of Focused Parathyroidectomy: A Contemporary Series of 845 Patients

HYPOTHESIS Focused parathyroidectomy guided by intraoperative parathyroid hormone monitoring (IPM) may lead to higher failure rates because of missed multiglandular disease. DESIGN Retrospective review of prospectively collected data. SETTING Tertiary referral center. PATIENTS From September 8, 1993, through January 30, 2009, a total of 845 consecutive patients with sporadic primary hyperparathyroidism underwent focused parathyroidectomy guided by IPM at a single institution. MAIN OUTCOME MEASURES Parathyroid hormone dynamics and perioperative data were analyzed for factors affecting outcome. Operative failure was defined as hypercalcemia with elevated parathyroid hormone levels within 6 months after parathyroidectomy. Detailed intraoperative data from the failed operations were also reviewed. RESULTS Of 723 patients followed up for at least 6 months, 702 (97.1%) had successful parathyroidectomy, and 21 (2.9%) had failed parathyroidectomy. The major cause of operative failure was the surgeons inability to find the abnormal parathyroid gland (16 of 21 patients [76.2%]). In the remaining patients, IPM results were false-positive in 5 of 21 patients (23.8%) or 0.7% overall. Among the cohort, IPM correctly identified missed multiglandular disease in 33 of 38 patients (86.8%). Patients having operative failure were more likely to have a history of thyroidectomy or parathyroidectomy and were less likely to have correct findings on technetium Tc 99m sestamibi or ultrasonographic localizing studies compared with patients having operative success. CONCLUSION Inability of the surgeon to find the abnormal parathyroid gland-not missed multiglandular disease-is the main cause of operative failure in focused parathyroidectomy guided by IPM.

Parathyroidectomy for hypercalcemic crisis: 40 years' experience and long-term outcomes

BACKGROUND Hypercalcemic crisis is a serious and potentially life-threatening complication of markedly increased serum calcium concentrations most commonly due to severe primary sporadic hyperparathyroidism (HPT). METHODS A review of 1,310 consecutive patients with severe sporadic HPT who underwent parathyroidectomy at a single institution from April 1970 through July 2009 was performed. Of this series, 88 patients were treated operatively for hypercalcemic crisis associated with signs and symptoms of acute calcium intoxication and/or serum calcium concentrations ≥14 mg/dL (3.5 mmol/L). Clinical presentation, laboratory values, operative success, operative failure, and disease recurrence were compared to noncrisis patients. RESULTS Preoperative calcium and parathyroid hormone (PTH) concentrations were significantly greater among patients with hypercalcemic crisis. Crisis patients had a greater incidence of mental status changes, fatigue, ectopic glands, and pancreatitis. Postoperatively, calcium and PTH levels were similar. Overall, crisis patients had a lesser rate of operative success compared to noncrisis patients (92% vs 97%). With the advent of intraoperative PTH monitoring-guided focused parathyroidectomy in 1993, success rates equalized (95% vs 97%). There was no difference in disease recurrence. Overall follow-up was 59 months. CONCLUSION Hypercalcemic crisis patients are appropriately treated by expeditious parathyroidectomy, but overall have slightly lesser rates of initial operative success than noncrisis patients. Long-term results reveal similar serum calcium, PTH concentrations, and recurrence rates at a mean follow-up of nearly 5 years.

Surgeon-performed ultrasound: A single institution experience in parathyroid localization

BACKGROUND Ultrasound has been used successfully to localize parathyroid glands. This study evaluates surgeon-performed ultrasound (SUS) for pre-operative parathyroid localization prior to parathyroidectomy. METHODS In all, 442 patients with primary hyperparathyroidism (HPT) underwent SUS at a single institution. Patients were divided into 2 groups: group 1 (n = 338) had correct localization, and group 2 (n = 104) had incorrect localization. The true-positive (TP) rate and peri-operative findings were compared. TP was defined as localization of all abnormal parathyroids resulting in operative success. A P value >.05 was considered significant. RESULTS Of 442 patients, 338 (76.5%) had TP results. Group 1 patients were younger (57 vs 63 years; P < .0001) with larger gland size: 2.1 versus 1.8 cm (P = .08). In group 2, 45/104 (43%) patients had false-positive SUS, and 59/104 (57%) had negative studies or missed multiglandular disease (MGD). Group 1 patients had shorter operative times (60 vs 80 min, P = .002), fewer bilateral neck explorations (BNEs) (8% vs 39%; P < .0001), and lower MGD rates (2% vs 19%; P < .0001). Operative failure was 0.3% in group 1 and 9.6% in group 2 (P < .0001). CONCLUSION Younger patients have a greater rate of correct localization. When SUS correlates with operative findings, MGD is significantly lower and fewer BNEs are performed. Additionally, operations are shorter with a higher success rate.

Use of Ultrasound in the Management of Thyroid Cancer

The use of ultrasound for thyroid cancer has evolved dramatically over the last few decades. Since the late 1960s, ultrasound has become essential in the examination of the thyroid gland with the increased availability of high-frequency linear array transducers and computer-enhanced imaging capabilities of modern day portable ultrasound equipment in a clinic- or office-based setting. As a noninvasive, rapid, and easily reproducible imaging study, ultrasound has been demonstrated to have a broadened utility beyond the simple confirmation of thyroid nodules and their sizes. Recently, office-based ultrasound has become an integral part of clinical practice, where it has demonstrated overwhelming benefits to patients being evaluated and treated for thyroid cancer. Ultrasound has become useful in the qualitative characterization of thyroid nodules based on benign or malignant features. On the basis of such classifications and the relative risk for thyroid malignancy, the need for ultrasound-guided fine-needle aspiration, preoperative and intraoperative staging, lymph node mapping, and the extent of surgery can subsequently be determined. Furthermore, ultrasound has additional value in the surveillance of patients treated for thyroid cancer.