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Background: Macroscopic extrathyroidal extension to structures adjacent to the thyroid gland is one of the most important predictors of survival in papillary thyroid carcinoma. However, the prognostic significance of macroscopic extrathyroidal extension to strap muscles alone is unknown. The aim of this study is to determine the impact on survival in patients with macroscopic extrathyroidal extension to strap muscles alone compared to those with no macroscopic extrathyroidal extension and macroscopic extrathyroidal extension involving other adjacent structures., Methods: After institutional review board approval, adult papillary thyroid carcinoma patients were identified from an institutional database of 6,259 patients undergoing initial surgery for well-differentiated thyroid carcinoma from 1986 to 2015. Patients were classified as having no macroscopic extrathyroidal extension, macroscopic extrathyroidal extension to strap muscles alone, or macroscopic extrathyroidal extension to other adjacent structures. Disease-specific survival was calculated using the Kaplan-Meier method and groups were compared using the log-rank test. A P value < .05 was considered statistically significant and significant factors were used in a Cox proportional hazard model to predict disease-specific survival., Results: There were 5,880 patients included in the analysis; 5,485 patients (93.3%) in the no macroscopic extrathyroidal extension group, 179 (3.0%) in the macroscopic extrathyroidal extension to strap muscles alone group and 216 (3.7%) in the macroscopic extrathyroidal extension involving other adjacent structures group. With a median follow-up of 64 months, the estimated 10-year disease-specific survival for patients with no macroscopic extrathyroidal extension, macroscopic extrathyroidal extension to strap muscles alone, and macroscopic extrathyroidal extension involving other adjacent structures were 98.9%, 95.7%, and 83.7%, respectively (P < .0001). In the ≥55-year-old cohort, the estimated 10-year disease-specific survival for patients with no macroscopic extrathyroidal extension, macroscopic extrathyroidal extension to strap muscles alone, and macroscopic extrathyroidal extension involving other adjacent structures were 97.6%, 89.3%, and 68.1%, respectively (P <.0001). After controlling for pathological nodal stage and distant metastasis stage, extent of extrathyroidal extension remained an independent predictor of disease-specific survival; patients with macroscopic extrathyroidal extension to strap muscles alone had a 3.3-fold increased likelihood of a disease-specific death compared to no macroscopic extrathyroidal extension patients (hazard ratio 3.294; 95% confidence interval 1.076-10.086, P < .0368)., Conclusion: In our study, patients aged ≥55 years with papillary thyroid carcinoma and macroscopic extrathyroidal extension to strap muscles alone appear to have an increased likelihood of a disease-specific death compared to patients with no macroscopic extrathyroidal extension., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: The approach for surgical treatment of patients with low-/intermediate-risk T1T2N0/Nx well-differentiated thyroid cancer (WDTC)-total thyroidectomy (TT) versus thyroid lobectomy (TL)-remains a controversial topic. Conducting a randomized controlled trial (RCT) would be the gold standard to address this issue. However, this is challenging due to excellent survival outcomes, and therefore, high number of patients and long-term follow-up would be required. As an alternative to RCT, we have used propensity score (PS) matching to determine if T1T2N0/Nx patients selected to have TL had equivalent outcomes to a similar group treated with TT. Methods: After institutional review board approval, a database of 6259 patients with WDTC treated with primary surgery at our institution between 1985 and 2016 was analyzed to identify patients with T1T2N0/Nx cancers. Of 3756 patients identified, 943 were managed by TL and 2813 by TT. To control for possible confounders and reduce potential bias, we selected age, sex, histology, 131 I therapy, American Thyroid Association risk, and American Joint Committee Cancer stage as our PS matching criteria. Subsequently, 918 TL patients were successfully matched with 918 TT patients. The Pearson χ 2 test or Fisher's exact test was used to compare categorical covariates, and Student's t -test was used for comparison of continuous variables between the two groups. Disease-specific survival (DSS), overall survival (OS), and recurrence-free survival (RFS) were calculated using the Kaplan-Meier method and compared using the log-rank test. Results: After PS matching, there were no significant differences between TL and TT patients for OS (10-year OS: 92.2% vs. 91.3%, p  = 0.9668), DSS (10-year DSS: 100% vs. 99.1%, p  = 0.1967), or RFS (10-year RFS: 99.5% vs. 98.3%, p  = 0.079). Conclusions: For low-/intermediate-risk patients with intrathyroidal thyroid cancer <4 cm, patients selected for TL have similar survival outcomes to a comparable group treated by TT.

Background: The 2015 American Thyroid Association guidelines state that a prophylactic central compartment neck dissection (PCND) should be considered for patients with papillary thyroid carcinoma (PTC) and clinically involved lateral neck lymph nodes (cN1b). The purpose of our study was to determine the rate of central neck recurrence in select cN1b patients, with no evidence of clinically involved central compartment lymph nodes, treated without a PCND., Methods: After institutional review board approval, adult PTC patients with cN1b disease who were treated with a total thyroidectomy and lateral neck dissection were identified from an institutional database of 6259 patients who underwent initial surgery for well-differentiated thyroid carcinoma from 1986 to 2015. Patients with gross extrathyroidal extension, distant metastases, or no preoperative imaging were excluded. Patients with evidence of clinically involved central compartment lymph nodes, on preoperative imaging or intraoperative evaluation, also were excluded. A total of 152 cN1b patients were included and categorized into non-PCND and PCND groups. Central neck recurrence-free probability (CNRFP) was calculated using the Kaplan-Meier method and log-rank tests., Results: One hundred three patients (67.8%) did not have a PCND. With a median follow-up of 65 months, the 5- and 10-year CNRFP was 98.4% in the non-PCND group and 93.6% in the PCND group (p = 0.133)., Conclusions: Select PTC patients with cN1b disease but no evidence of clinically involved central compartment lymph nodes, on preoperative imaging and intraoperative evaluation, appear to have a low rate of central neck recurrence. These patients may not require or benefit from a PCND.

Background: Retropharyngeal lymph node metastases (RPMs) from differentiated thyroid carcinoma (DTC) are rare. Treatment includes surgical resection, radioactive iodine (RAI) therapy, or external beam radiation therapy (EBRT). The objective of this study was to describe our experience in the management of DTC-associated RPMs. Methods: Patients diagnosed with a DTC-associated RPM from 1999 to 2018 were identified at our institution, using key search terms in imaging and histology reports. Patient and tumor characteristics were recorded, and patients were grouped according to RPM management: observation, nonsurgical treatment, or surgical resection. The estimated rates of local RPM control, disease-specific survival (DSS), and distant metastasis-free probability (DMFP) were calculated by using the Kaplan-Meier method. Results: Of the 65 patients identified, 53 (82%) had an RPM as a manifestation of recurrent disease. Twenty-five patients (38%) underwent observation, 13 (20%) received nonsurgical treatment (RAI, EBRT, and/or systemic therapy), and 27 (42%) underwent surgical resection. In the observation cohort, all patients had a stable RPM, which in the majority (80%) of cases remained <1.5 cm during the period of observation (median 28 months). Of the 13 patients in the nonsurgical treatment cohort, 3 received RAI therapy, 7 received EBRT, and 3 received systemic therapy only. In the surgical cohort, the median RPM maximum diameter was 2.0 cm (range 0.8-4.2 cm). The size of the RPM was predictive of surgical resection versus observation ( p  < 0.001). A transcervical approach was employed in 19 patients, and a transoral approach was used in 8 patients. The 5-year rate of local RPM control was 92%. For the whole cohort, the 5- and 10-year DMFP were 72% and 62%, respectively; the 5- and 10-year DSS were 93% and 81%, respectively. Conclusions: DTC-associated RPMs manifest as recurrent disease in the majority of patients. Select patients with a small-volume and nonprogressive RPM may be suitable for observation, whereas surgery is likely warranted in large or progressing RPMs. In general, the presence of an RPM from DTC appears to be associated with aggressive disease.

Background: Multifocality in papillary thyroid carcinoma is common. The aim of this study is to determine whether patients with multifocal disease, treated with lobectomy alone, have an increased risk of contralateral lobe papillary thyroid carcinoma, regional recurrence, and poorer survival., Methods: After institutional review board approval, papillary thyroid carcinoma patients managed from 1986 to 2015 with lobectomy alone were identified from an institutional database. Papillary thyroid carcinoma patients with pT3 to T4 classification, nodal disease, or distant metastases were excluded. After excluding 40 patients who underwent an immediate completion thyroidectomy, 849 were included in the analysis; 619 (72.9%) had unifocal disease and 230 (27.1%) had multifocal disease. Contralateral lobe papillary thyroid carcinoma-free probability, regional recurrence-free probability, disease-specific survival, and overall survival were calculated using the Kaplan-Meier method., Results: With a median follow-up of 58 months, unifocal disease and multifocal disease patients had similar rates of contralateral lobe papillary thyroid carcinoma, regional recurrence, and overall survival (10-year contralateral lobe papillary thyroid carcinoma-free probability 98.6% vs 97.8%; regional recurrence-free probability 99.5% vs 99.4%; overall survival 91.6% vs 93.1%, respectively). There were no disease-related deaths., Conclusion: Select multifocal disease patients, managed with lobectomy alone, have rates of contralateral lobe papillary thyroid carcinoma, regional recurrence, and overall survival comparable to unifocal disease patients. Multifocal disease should not be an indication for completion thyroidectomy., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Preoperative detection of RAS mutations can contribute to cancer risk assessment in indeterminate thyroid nodules, although RAS is not always associated with malignancy., Methods: Fine-needle aspiration samples classified in 1 of 3 indeterminate cytology categories were prospectively tested for N-, H-, and K-RAS mutations using next-generation sequencing assay., Results: In the study, 93 patients with 94 nodules had preoperative RAS detected, of whom 86 patients had an operation (69% total thyroidectomy, 29% lobectomy). In total, 76% of RAS-positive nodules were malignant and follicular variant papillary thyroid cancer was the most common cancer type (83%). HRAS mutations had the greatest risk of cancer (92%) followed by NRAS (74%) and KRAS (64%; P = .05). No preoperative variables were associated with malignancy including age (P = .07), sex (P = .49), RAS isoform (P = .05), mutational allelic frequency (P = .49), nodule size (P = .14), cytology category (P = .63), or ultrasound bilaterality (P = .24), multifocality (P = .23), or presence of ≥1 suspicious feature (P = .86). Only 60% of patients with a unifocal nodule on ultrasound had single focus low-risk encapsulated follicular variant papillary thyroid cancer or benign disease., Conclusion: Preoperative RAS mutation detection in thyroid nodules carries a substantial risk of cancer with a greater risk associated with HRAS and NRAS. Most RAS malignancies are follicular variant papillary thyroid cancer, which may inform the extent of operation., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: The majority of differentiated thyroid cancer tends to present with limited locoregional disease, leading to excellent long-term survival after operative treatment. Even patients with advanced local disease may survive for long periods with appropriate treatment. The aim of this study is to present our institutional experience of the management of locally advanced differentiated thyroid cancer and to analyze factors predictive of outcome., Methods: We reviewed our institutional database of 3,664 previously untreated patients with differentiated thyroid cancer operated between 1986 and 2010. A total of 153 patients had tumor extension beyond the thyroid capsule that invaded the subcutaneous soft tissues, recurrent laryngeal nerve, larynx, trachea, or esophagus. Details on extent of operation and adjuvant therapy were recorded. Disease-specific survival and locoregional recurrence-free probability were determined by the Kaplan-Meier method. Factors predictive of outcome were determined by multivariate analysis., Results: The median age of the 153 patients with tumor extension beyond the thyroid capsule was 55 years (range 11-91 years). Eighty-nine patients (58.2%) were female. Twenty-three patients (15.0%) were staged as M1 at presentation, and 122 (79.7%) had pathologically involved lymph nodes. The most common site of extrathyroidal extension was the recurrent laryngeal nerve (51.0%) followed by the trachea (46.4%) and esophagus (39.2%). Sixty-three patients (41%) required resection of the recurrent laryngeal nerve due to tumor involvement. After surgery, 20 patients (13.0%) had gross residual disease (R2), 63 (41.2%) had a positive margin of resection (R1), and 70 (45.8%) had complete resection with negative margins (R0). With a median follow-up of 63.9 months, 5-year, disease-specific survival, when stratified by R0/R1/R2 resection, was 94.4%, 87.6%, and 67.9%, respectively (P = .030). The data do not demonstrate a statistical difference in survival between R0 versus R1 (P = .222). The 5-year distant recurrence-free probability for M0 patients was 90.8%, 90.3%, and 70.7% (P = .410). The locoregional recurrence-free probability was 85.8% for R0 patients and 85.5% for R1 patients (P = .593)., Conclusion: With an appropriate operative strategy, patients with locally advanced thyroid cancer with an R0 or R1 resection have excellent survival outcome., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Predictive role of undetectable thyroglobulin (Tg) in patients with poorly differentiated thyroid carcinoma (PDTC) is unclear. Our goal was to report on Tg levels following total thyroidectomy and adjuvant RAI in PDTC patients and to correlate Tg levels with recurrence., Methods: Forty patients with PDTC with no distant metastases at presentation (M0) and managed by total thyroidectomy and adjuvant RAI were identified from a database of 91 PDTC patients. Of these, 31 patients had Tg values recorded and formed the basis of our analysis. A nonstimulated Tg level <1 ng/ml was used as a cutoff point for undetectable Tg levels. Association of patient and tumor characteristics with Tg levels was examined by χ (2) test. Recurrence-free survival (RFS) stratified by postop Tg level was calculated by Kaplan-Meier method and compared by log-rank test., Results: Twenty patients had undetectable Tg (<1 ng/ml) and 11 had detectable Tg (≥1 ng/ml; range 2-129 ng/ml) following surgery. After adjuvant RAI, 24 patients had undetectable Tg (<1 ng/ml) and 7 had detectable Tg (≥1 ng/ml; range 1-57 ng/ml). Patients with undetectable Tg were less likely to have pathologically positive margins compared to those with detectable Tg (33 vs. 72 % respectively; p = 0.03). Patients with undetectable Tg levels had better 5-year regional control and distant control than patients with detectable Tg level (5-year regional recurrence-free survival 96 vs. 69 %; p = 0.03; 5-year distant recurrence-free survival 96 vs. 46 %, p = 0.11)., Conclusion: Postoperative thyroglobulin levels in subset of patients with PDTC appear to have predictive value for recurrence. Patients with undetectable Tg have a low rate of recurrence.

Background: In contrast to other head and neck cancers, the impact of histological thyroid specimen margin status in differentiated thyroid cancer (DTC) is not well understood. The aim of this study was to investigate the prognostic value of margin status on local recurrence in DTC., Method: The records of 3664 consecutive patients treated surgically for DTC between 1986 and 2010 were identified from an institutional database. Patients with less than total thyroidectomy, unresectable or gross residual disease, or M1 disease at presentation and those with unknown pathological margin status were excluded from analysis. In total, 2616 patients were included in the study; 2348 patients (90%) had negative margins and 268 patients (10%) had positive margins. Microscopic positive margin status was defined as tumor present at the specimen's edge on pathological analysis. Patient, tumor, and treatment characteristics were compared by Pearson's chi-squared test. Local recurrence free survival (LRFS) was calculated for each group using the Kaplan Meier method., Results: The median age of the cohort was 48 years (range 7-91 years) and the median follow-up was 50 months (range 1-330 months). Age, sex, and histology types were similar between groups. As expected, patients who had positive margins were more likely to have larger tumors (p<0.001), extrathyroidal extension (ETE) (p<0.001), multicentric disease (p<0.001), or nodal disease (p<0.001) and were more likely to receive adjuvant radioactive iodine therapy (p<0.001) as well as external beam radiotherapy (p<0.001). The LRFS at 5 years for patients with positive margins status was slightly poorer compared with patients with negative margins (98.9% vs. 99.5%, p=0.018). Twelve patients developed local recurrence-8/2348 (0.34%) patients with negative margins and 4/263 (1.52%) patients with positive margins. Univariate predictors of LRFS were sex (p=0.006), gross ETE (<0.001), and positive margins (p=0.018). However, when controlling for presence of gross ETE on multivariate analysis, microscopic positive margin status was not an independent predictor of LRFS (p=0.193)., Conclusion: Patients with resectable, M0 disease that undergo total thyroidectomy have an excellent five year LRFS of 99.4%. Microscopic positive margin status was not a significant predictor for local failure after adjusting for ETE or pathological tumor (pT) stage.

Introduction: The current American Joint Committee on Cancer TNM classification for differentiated thyroid cancer (DTC) separates T1 status into T1a and T1b based on a 1-cm cutoff for maximal tumor dimension. In 2009, the American Thyroid Association recommended total thyroidectomy for tumors >1 cm in contrast to the possibility of lobectomy for tumors ≤ 1 cm. Our aim was to investigate the prognostic significance of a 1-cm tumor cutoff., Methods: From an institutional database of 3,664 patients with DTC, 1,522 patients with T1 tumors without neck disease or distant metastases were identified. Patient, tumor, and treatment characteristics were compared. Disease-specific survival (DSS) and recurrence-free survival (RFS) outcomes were analyzed., Results: Total thyroidectomy rates were similar between patients with T1a and T1b tumors (P = .307). With a median follow-up of 46 months (range, 1-320), there were no disease-specific deaths in the T1a or T1b groups. In total, 18 patients (1.2%) experienced a recurrence. Five-year RFS was comparable for patients with T1a and T1b tumors (98.6 vs 98.6%; P = .224)., Conclusion: T1a and T1b tumors have similar prognosis both in terms of DSS and RFS. It seems that a distinction between tumors of <1 and >1 cm is of no prognostic benefit., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: The impact of preoperative neck ultrasound (US) on management of the lateral neck in patients with differentiated thyroid cancer is unclear. The objective of this study was to assess the impact of preoperative neck US on the rate of lateral neck dissection in clinical N0 neck and initial response to therapy., Methods: An institutional review board-approved retrospective review of 890 patients that had thyroid surgery for differentiated thyroid cancer between 2009 and 2010 was performed at our institution. Patients with palpable neck disease, distant metastases, less than total thyroidectomy, no postoperative thyroglobulin (Tg) determinations, and positive Tg antibodies were excluded, leaving 465 patients available for analysis. Patients were divided into those who had a preoperative neck US to evaluate lateral neck nodes (n = 234) and those who did not (n = 231). Patient and tumor characteristics were compared using the χ(2) test. The primary end point was response to therapy, defined by postoperative US and Tg levels., Results: There were no significant differences in age, histology, T stage, postoperative radioactive iodine dose, American Joint Committee on Cancer stage, American Thyroid Association risk category, or duration of follow up between the 2 groups. Patients with preoperative neck US were more likely to have lateral neck dissection compared with patients without preoperative neck US [n = 31 (13.2%) vs n = 2 (0.9%); P < .001]. Preoperative neck US resulted in a better response to therapy (P = 0.005), a greater likelihood of no evidence of disease, and a smaller likelihood of having a biochemical or structural incomplete response or a return for delayed neck dissection. The preoperative US group also resulted in fewer recurrences; 10 patients from the no preoperative US group returned to the operating room compared with two patients (4.3% vs 0.9%, P = .018) who had a preoperative neck US., Conclusion: Preoperative neck US detects more lateral neck disease, leading to an increase in lateral neck dissection with subsequent improvement in response to therapy and fewer return to the operating room for regional recurrence management.

Background: At our institution, thyroid lobectomy is employed as a definitive operation for unifocal intrathyroidal low risk cancers and thus completion thyroidectomy is rarely performed. The purpose of this study was to identify the indications for selective completion thyroidectomy and to report oncologic outcomes., Methods: A retrospective review was performed to identify patients who underwent planned completion thyroidectomy for well-differentiated thyroid carcinoma (WDTC) from 2001 to 2010 based on initial lobectomy pathology. Assessment for risk of recurrence was based on the American Thyroid Association Initial Risk Stratification., Results: During the 10-year study period, 79 patients underwent completion thyroidectomy for WDTC. Forty-four (56 %) patients were low risk and 35 (44 %) were intermediate risk. Completion thyroidectomy was recommended for 64 patients, whereas 15 patients were given an option of surveillance but ultimately decided to have surgery. Patients in the "recommended group" had more T3 tumors and fewer T1a tumors (p = 0.005 and 0.006, respectively). These patients also were more likely to be intermediate risk (p = 0.008) and to present with aggressive histology (p = 0.002). The rate of contralateral tumors (n = 27) was similar between both groups (35 and 33 %, respectively). Contralateral cancers were micropapillary in 24 of 27 (89 %) patients, 10 (40 %) of whom had multifocal disease. There were two pulmonary recurrences and no local-regional recurrences (median follow-up of 42.3 months)., Conclusions: Completion thyroidectomy is infrequent and performed for a select group of intermediate and low risk WDTCs at our institution with low recurrence rates. Incidental multifocal and unifocal contralateral cancers are common after completion thyroidectomy.

Background: Cervical hematoma can be a potentially fatal complication after thyroidectomy, but its risk factors and timing remain poorly understood., Methods: We conducted a retrospective, case-control study identifying 207 patients from 15 institutions in 3 countries who developed a hematoma requiring return to the operating room (OR) after thyroidectomy., Results: Forty-seven percent of hematoma patients returned to the OR within 6 hours and 79% within 24 hours of their thyroidectomy. On univariate analysis, hematoma patients were older, more likely to be male, smokers, on active antiplatelet/anticoagulation medications, have Graves' disease, a bilateral thyroidectomy, a drain placed, a concurrent parathyroidectomy, and benign pathology. Hematoma patients also had more blood loss, larger thyroids, lower temperatures, and higher blood pressures postoperatively. On multivariate analysis, independent associations with hematoma were use of a drain (odds ratio, 2.79), Graves' disease (odds ratio, 2.43), benign pathology (odds ratio, 2.22), antiplatelet/anticoagulation medications (odds ratio, 2.12), use of a hemostatic agent (odds ratio, 1.97), and increased thyroid mass (odds ratio, 1.01)., Conclusion: A significant number of patients with a postoperative hematoma present >6 hours after thyroidectomy. Hematoma is associated with patients who have a drain or hemostatic agent, have Graves' disease, are actively using antiplatelet/anticoagulation medications or have large thyroids. Surgeons should consider these factors when individualizing patient disposition after thyroidectomy., (Copyright © 2013 Mosby, Inc. All rights reserved.)

Background: The American Thyroid Association guidelines recommend the routine use of radioactive iodine for remnant ablation (RRA) in all T3 or greater primary tumors, and selective use in patients with intrathyroidal disease >1 cm, or evidence of nodal metastases. The guidelines recognize that there is conflicting and inadequate data to make firm recommendations for most patients. The aim of this study was to analyze our institutional experience of the use of RRA in the management of papillary thyroid cancer, with a particular focus on outcomes for those patients selected not to receive RRA., Methods: We retrospectively reviewed 1129 consecutive patients who underwent total thyroidectomy at the Memorial Sloan-Kettering Cancer Center between 1986 and 2005. Of these, 490 were pT1-2 N0, 193 pT1-2 N1, and 444 pT3-4. Details on recurrence and disease-specific survival were recorded by the Kaplan-Meier method and compared using the log-rank test., Results: The five-year disease-specific survival and recurrence-free survival in the pT1/T2 N0, pT1-2 N1, and pT3-4 were 100% and 92%, 100% and 92%, and 98% and 87% respectively. Low-risk patients who were managed without RRA (who tended to have limited primary disease, pT1-2, and low-volume metastatic disease in the neck, pT1-2 N1-fewer than five nodes, all <1 cm greatest dimension) had five-year recurrence-free survival of >97%. In the group with advanced local tumors (pT3-4), those patients who did not receive RRA (who tended to have pT3 N0 disease) had five-year recurrence-free survival of >90%., Conclusion: Following appropriate surgical management, the majority of patients with low-risk local disease and even some patients with more advanced-stage (pT3) tumors or regional metastases have low rates of recurrence and high rates of survival when managed without RRA.

Background: The efficacy of radioactive iodine therapy (RAI) in patients who have an undetectable thyroglobulin (Tg) level after total thyroidectomy in well-differentiated papillary thyroid cancer (PTC) is questionable. The objectives of this study were to report the risk of recurrence in patients with PTC who had an undetectable Tg level after total thyroidectomy managed with postoperative RAI and without RAI., Methods: After approval by the institutional review board, 751 consecutive patients who had total thyroidectomy for PTC as well as postoperative Tg measurement were identified from our institutional database of 1163 patients treated for well-differentiated thyroid carcinoma at Memorial Sloan Kettering Cancer Center between 1999 and 2005. Of these, 424 patients had an undetectable postoperative Tg (defined as a Tg <1 ng/mL) of whom 80 were classified as low, 218 intermediate, and 126 high risk via use of the GAMES (grade, age, distant metastasis, extrathyroidal extension, and size of the neoplasm) criteria. Patient, neoplasm, and treatment characteristics were recorded on the low- and intermediate-risk patients. Recurrence was defined as any structural abnormality on examination or imaging and confirmed by fine-needle aspiration biopsy. Disease-specific survival and recurrence-free survival (RFS) were calculated with the Kaplan-Meier method. Univariate analysis was carried out by the log rank test and multivariate analysis by Cox proportional hazards method., Results: In the low-risk group (n = 80), 35 patients received postoperative RAI and 45 did not. Comparison of patient and tumor characteristics showed patients treated without RAI were more likely to have T1 tumors (82% vs 60%, P = .027). There were no disease-specific deaths in either group. There was 1 neck recurrence in the group that did not receive RAI. Patients managed without RAI had a similar RFS to patients managed with RAI (96% vs 100%, P = .337). In the intermediate risk group (n = 218), 135 were managed with RAI and 83 without. Comparison of patient and tumor characteristics showed patients managed without RAI were more likely to be older patients (≥ 45 years: 90% vs 39%, P < .0005) with smaller tumors (pT1T2: 97% vs 62%, P < .0005) and negative neck disease (N0: 56% vs 30%, P < .0005). There were no disease specific deaths in either group. There were 7 recurrences, of which 6 were in the RAI cohort (5 regional, 1 distant) and 1 in the non-RAI cohort (1 regional). Patients managed without RAI had a similar RFS to patients managed with RAI (97% vs 96%, P = .234)., Conclusion: Select low- and intermediate-risk group patients who have undetectable Tg after total thyroidectomy for PTC can be managed safely without adjuvant RAI with no increase in risk of recurrence., (Copyright © 2012 Mosby, Inc. All rights reserved.)

Objective: To report the impact of microscopic extrathyroid extension (ETE) on outcome in patients with cT1/cT2 well-differentiated thyroid cancer (WDTC), and to determine the effect of extent of surgery and adjuvant radioactive iodine (RAI) treatment on outcome in patients with microscopic ETE., Patients and Methods: From an institutional database, we identified 984 patients (54%) who underwent surgery for cT1/T2N0 disease. Of these, 869 patients were pT1/T2 and 115 were upstaged to pT3 based on the finding of microscopic ETE. Disease-specific survival (DSS) and recurrence-free survival (RFS) were analyzed for each group using the Kaplan-Meier method. In the pT3 group, factors predictive of outcome were analyzed by univariate and multivariate analyses., Results: There was no difference in the 10-year DSS (99% vs 100%; P = .733) or RFS (98% vs 95%; P = .188) on comparison of the pT1/pT2 and pT3 cohorts. Extent of surgery and administration of postoperative RAI were not significant for recurrence on univariate or multivariate analysis in the pT3 cohort., Conclusion: Outcomes in patients with cT1T2N0 WDTC are excellent and not affected by microscopic ETE. The extent of resection and administration of postoperative RAI in patients with microscopic ETE does not impact survival or recurrence., (Copyright © 2011 Mosby, Inc. All rights reserved.)

Objective: To develop statistical prediction tools to select patients for short-stay thyroidectomy based on dynamic quantification of individual risk for postoperative hypocalcemia., Design: Clinical and biochemical factors that could influence postoperative calcium levels were analyzed. A multivariable logistic regression model was used to study the predictive ability of each variable for hypocalcemia. A step-down model reduction selection method was used to rank the predictors according to their predictive accuracy., Setting: Memorial Sloan Kettering Cancer Center., Patients: A test population of 393 patients who met our inclusion criteria and who underwent total thyroidectomy at Memorial Sloan Kettering Cancer Center in the year 2008 made up the modeling data set, 116 of whom developed biochemical hypocalcemia postoperatively (29.5%). The nomograms were validated on an independent data set consisting of 296 selected patients who underwent total thyroidectomy during the year 2005, using the same selection criteria for inclusion as those for the modeling data set., Main Outcome Measures: The 8 predictors with the highest predictive accuracy were selected to generate a nomogram, which was validated both internally and externally using an independent data set. A second nomogram was developed for assessing the probability of a patient stay of 24 hours or shorter, based on preoperative and intraoperative factors., Results: The 8 variables of highest predictive value were age, sex, medications, history of cancer, preoperative serum calcium level, creatinine concentration, central neck dissection, and alkaline phosphatase levels. A nomogram was created based on the final parsimonious model. The nomogram had excellent accuracy (concordance index of 74.6%) and scored high on internal validation tests. The concordance index of the second nomogram for predicting the likelihood of discharge from the hospital within 24 hours was 70%., Conclusion: We have produced a set of nomograms that can dynamically quantify the risk of postthyroidectomy hypocalcemia and prolonged hospital stay based on preoperative clinical and biochemical variables and intraoperative surgical variables.

Objective: The objective of this study was to determine the incidence and significance of Delphian node (DN) metastasis in papillary thyroid cancer., Summary of Background Data: Despite the historic association, the prognostic implications of thyroid cancer metastasis to the DN remain unclear., Methods: Retrospective analysis of 101 patients who underwent thyroid surgery from 2007 to 2009 for papillary thyroid cancer, and had their DN harvested ab initio. Of these, 25 had metastatic disease to the DN. DN status was correlated with clinical and pathologic factors including age, gender, tumor size, histologic variant, extra-thyroidal extension (ETE), and central and lateral nodal metastasis., Results: DN positivity was seen consequent to higher rates of ETE of the primary tumor (52% vs. 28%; P = 0.025) and is associated with further nodal metastases to the central (72% vs. 22%; P < 0.0001) and lateral (28% vs. 4%; P < 0.0001) neck compartments. DN positivity was also associated with heavier nodal burden, in terms of number of metastatic nodes (median 5 vs. 2 nodes; P = 0.005) and nodal size (median 1 cm vs. 0.5 cm; P = 0.03)., Conclusions: Metastatic involvement of the DN is often associated with ETE and increased incidence of metastatic disease to the central and lateral neck compartments. If the DN is positive on intraoperative frozen section, careful evaluation of the central and lateral nodal compartments is essential., (@ 2011 Lippincott Williams & Wilkins, Inc.)

Background: The American Thyroid Association guidelines do not mention isthmusectomy as an appropriate procedure for thyroid cancer. Despite this, a small number of patients present with lesions isolated to the thyroid isthmus, which can be excised without exploring the trachyesophageal grooves or total thyroidectomy. This study was designed to analyze outcomes in patients treated with isthmusectomy for small well-differentiated thyroid cancer (WDTC) at our institution., Methods: Nineteen patients with WDTC managed by isthmusectomy were identified from a database of 1,810 patients (1%) with WDTC managed by surgery in Memorial Sloan Kettering Cancer Center from 1986-2005. Demographic, surgical, pathological, and outcomes data were analyzed., Results: Six patients were men and 13 were women. The median age was 46 (range, 28-83) years. All patients had a solitary nodule confined to the thyroid isthmus. The median size of lesion was 1 (range, 0.4-3) cm. Eighteen patients had a pathologically T1 lesion (pT1), and one patient had a pT2 lesion. Two patients had papillary carcinoma detected in perithyroid lymph nodes (pN1a). There were no complications of recurrent laryngeal nerve palsy or hypocalcaemia. With a median follow-up of 124 (range, 53-276) months, the 10-year disease-specific survival was 100% and 100% local and regional 10-year recurrence-free survival., Conclusions: Our results suggest that isthmusectomy alone may be sufficient treatment for selected patients with small WDTC limited to the isthmus. This procedure has the benefit of avoiding dissection of the recurrent laryngeal nerve and parathyroid glands, thus limiting postoperative complications.

Background: Metastases to the thyroid gland are uncommon, with rates reported between 0.02% and 1.4% of surgically resected thyroid specimens. Our goal was to present our experience with surgical management of metastases to the thyroid gland., Methods: Twenty-one patients with metastatic disease to the thyroid were identified from a database of 1,992 patients with thyroid cancer who had surgery during 1986-2005. Patient, tumor, treatment, and outcome details were recorded by analysis of charts. The median age at time of surgery was 68 (range, 39-83) years; 12 were men and 9 were women., Results: All patients were managed by surgery, including lobectomy in ten patients, total thyroidectomy in six, completion thyroidectomy in two, and subtotal thyroidectomy in one. In two patients, the thyroid lesion was found to be unresectable at the time of surgery. Histopathology revealed renal cell carcinoma in ten, malignant melanoma in three, gastrointestinal adenocarcinoma in three, breast cancer in one, sarcoma in one, and adenocarcinoma from an unknown primary site in three patients. Seventeen patients have died. The cause of death in all 17 was widespread metastatic disease from their respective primary tumors. The median survival from surgery to death or last follow-up was 26.5 (range, 2-114) months., Conclusions: In patients with metastases to the thyroid gland, local control of metastatic disease in the central compartment of the neck can be successfully achieved with minimal morbidity with surgical resection in selected patients.

Background: Electronic synoptic operative reports ensure systematic documentation of all critical components and findings during complex surgical procedures. Thyroid surgery lends itself to synoptic reporting, because there are a predefined number of essential intraoperative events and findings that every endocrine surgeon invariably records., Methods: An electronic web-based form (e-form) was designed and implemented to record operative data in a synoptic structure for thyroid surgery. The e-form was implemented as a pilot study from January 2008 to October 2009 for use by three attending surgeons., Results: During this period, 514 e-forms were completed with 100% compliance, which recorded data from 384 total thyroidectomies and 130 thyroid lobectomies. All users found the e-form to be easy to use, comprehensive, and took less than 5 min to complete., Conclusions: The main advantages of a web-based e-form for synoptic recording of thyroid surgery are that it is user-friendly and easy to complete, yet comprehensive. Because it is based on a system available across institutions, it can be used as a minimum dataset and could be considered a national and international standard for wider use, especially if endorsed by the American or International Association for Endocrine Surgeons.

A technique of thyroidectomy that facilitates resection of the thyroid, preserves the parathyroid glands with their blood supply, and preserves the recurrent and the superior laryngeal nerves is described. This technique provides a simple and versatile means of complete extracapsular thyroidectomy for lesions of the thyroid gland and minimizes postoperative complications.

Objectives: To assess the incidence of unintentional parathyroid removal during routine thyroidectomy and to identify factors that might predict patients at high risk., Study Design: Retrospective review of case records. Data analyzed for incidental finding of parathyroid gland(s) in the thyroidectomy specimen and postoperative temporary or permanent hypocalcemia., Methods: The clinical records of 220 patients undergoing thyroidectomies between January 1997 and October 1999 were reviewed. Pathology reports were screened for information on the presence of parathyroid tissue along with the thyroid specimen. Operative reports were reviewed to exclude the possibility of intentional parathyroid gland removal. Case records were scrutinized to determine whether the patient developed symptomatic hypocalcemia postoperatively., Results: Nine percent of the 220 patients were found to have had inadvertent removal of parathyroid tissue. The majority of patients (95%) had two or less parathyroid glands in their specimens. The size and histological nature of the thyroid lesion were not predictive of inadvertent parathyroid removal. Of the 25 repeat operations for recurrent or persistent malignancy, 5 (20%) were found to have unintentional parathyroid removal compared with 15 (7.71%) of 195 primary thyroidectomy cases (P <.05). Nineteen percent of patients who had tracheoesophageal groove node dissection had an incidental parathyroid in their specimen compared with 7% who did not undergo tracheoesophageal groove node dissection (P = .04). None of the patients with unintentional parathyroid gland removal developed either temporary or permanent postoperative hypocalcemia., Conclusions: Inadvertent excision of a parathyroid gland(s) occurred in 9% of patients undergoing thyroidectomy in our experience. Reoperative thyroid surgery and tracheoesophageal node dissection were associated with a significantly higher risk of inadvertent parathyroid gland excision. Inadvertent parathyroidectomy did not result in symptomatic temporary or permanent hypocalcemia postoperatively.

Background Following total thyroidectomy ( TT) for papillary thyroid cancer ( PTC), pathological assessment can occasionally reveal incidental perithyroidal lymph nodes ( LNs) with occult metastases. These cN0pN1a patients often receive radioactive iodine ( RAI) therapy for this indication alone . The aim of this study was to determine the central compartment nodal recurrence-free survival in patients treated without RAI compared to those who received RAI treatment. Methods An institutional database of 3664 previously untreated patients with differentiated thyroid cancer operated between 1986 and 2010 was reviewed. A total of 232 pT1-3 patients managed with TT and no neck dissection were subsequently found to have incidental level 6 LNs on pathology. Patients with other indications for RAI, such as extrathyroidal extension and close or positive margins, were excluded. One hundred and four patients remained for analysis. Kaplan-Meier method was used to determine central neck LN recurrence-free survival ( RFS). Results The median age of the cohort was 40 years (range 17-83). The median follow-up was 53 months (range 1-211). The median number of positive LNs removed and maximum LN diameter were 1 (range 1-8) and 5 mm (range 1-16 mm), respectively. A total of 67 (64%) patients had adjuvant RAI and 37 (36%) did not. Patients with vascular invasion ( P = 0·01), LNs >2 mm ( P = 0·07) and >2 positive nodes ( P = 0·06) were more likely to be selected for adjuvant RAI therapy. Patients without RAI therapy had similar 5-year central neck LN RFS compared to those treated with RAI: 96·2% vs 94·6%, respectively ( P = 0·92). Conclusion There is no difference in the 5-year central compartment nodal recurrence-free survival in patients treated without RAI compared to those who received RAI treatment. [ABSTRACT FROM AUTHOR]

Background: The recent overdiagnosis of subclinical, low-risk papillary thyroid cancer (PTC) coincides with a growing national interest in cost-effective health care practices. The aim of this study was to measure the relative cost-effectiveness of disease surveillance of low-risk PTC patients versus intermediate- and high-risk patients in accordance with American Thyroid Association risk categories.Methods: Two thousand nine hundred thirty-two patients who underwent thyroidectomy for differentiated thyroid cancer between 2000 and 2010 were identified from the institutional database; 1845 patients were excluded because they had non-PTC cancer, underwent less than total thyroidectomy, had a secondary cancer, or had <36 months of follow-up. In total, 1087 were included for analysis. The numbers of postoperative blood tests, imaging scans and biopsies, clinician office visits, and recurrence events were recorded for the first 36 months of follow-up. Costs of surveillance were determined with the Physician Fee Schedule and Clinical Lab Fee Schedule of the Centers for Medicare and Medicaid Services.Results: The median age was 44 years (range, 7-83 years). In the first 36 months after thyroidectomy, there were 3, 44, and 22 recurrences (0.8%, 7.8%, and 13.4%) in the low-, intermediate-, and high-risk categories, respectively. The cost of surveillance for each recurrence detected was US $147,819, US $22,434, and US $20,680, respectively.Conclusions: The cost to detect a recurrence in a low-risk patient is more than 6 and 7 times greater than the cost for intermediate- and high-risk PTC patients. It is difficult to justify this allocation of resources to the surveillance of low-risk patients. Surveillance strategies for the low-risk group should, therefore, be restructured. [ABSTRACT FROM AUTHOR]

Background: The prognostic implications of the diagnosis of a papillary thyroid carcinoma (PTC) with tall-cell features are unknown. Methods: All PTC patients identified between 1985 and 2005 were analyzed histologically. Classical PTC cases were defined as having <30% tall cells, PTC with tall-cell features (PTC TCF) as 30%-49% tall cells, and tall-cell variant of PTC (TCV) as ≥50% tall cells. All classical PTC, PTC TCF, and TCV ≥1 cm in size were included. Results: A total of 453 patients satisfied the inclusion criteria (288 classical PTC, 31 PTC TCF, and 134 TCV). Classical PTC patients were younger than their PTC TCF and TCV counterparts ( p<0.0002). There was an increase in tumor size from classical PTC to PTC TCF and TCV ( p=0.05). Extensive extrathyroid extension and positive margins were more often present in TCV and PTC TCF than in classical PTC ( p=0.0001 and p=0.03 respectively). Overall pathologic tumor (pT) stage was more advanced in TCV and PTC TCF than in classical PTC ( p<0.0001). Total thyroidectomy and radioactive iodine therapy were more often performed and administered in TCV patients than in their PTC TCF and classical PTC counterparts ( p=0.001 and p=0.0001 respectively). Median follow-up was 9.3 years. Ten-year disease-specific survival (DSS) was lower in TCV (96%) and PTC TCF (91%) than in classical PTC (100%; p<0.001). Ten-year distant recurrence-free survival (RFS) was higher in classical PTC (98%) than in PTC TCF (89%) and TCV (96%; p=0.03). In multivariate analysis, the presence of more than five positive nodes and extranodal extension were the only independent prognostic factors of neck and distant RFS respectively. Four (2.4%) of 165 PTC TCF and PTC TCV developed poorly differentiated or anaplastic carcinoma in their recurrence, while none of the 288 classical PTC transformed into higher grades ( p=0.017). Conclusions: PTC TCF and TCV have similar clinicopathologic features that are more aggressive than classical PTC. PTC TCF and TCV have similar DSS and distant RFS but poorer outcomes than classical PTC. PTC TCF are currently being treated like classical PTC, that is, less aggressively than TCV. PTC TCF and TCV TCV have a higher rates of high-grade transformation than classical PTC. Consideration should be given to using a 30% tall-cell threshold to diagnose TCV. [ABSTRACT FROM AUTHOR]

Background: Distant metastases at presentation are rare in well-differentiated thyroid cancer (WDTC). The objective of this study was to report outcomes for patients presenting with distant metastases managed by thyroidectomy and radioactive iodine (RAI) therapy. Methods: Fifty-two patients with distant metastases from thyroid cancer diagnosed before thyroid surgery ( n=32) or on a postoperative RAI scan after thyroid surgery ( n=20) were identified from a database of patients with WDTC treated between 1985 and 2005. The median age was 58 years (range 12-83 years), with a male-to-female ratio of 3:2. Forty-seven patients (90%) had total thyroidectomy and two (4%) had thyroid lobectomy, and three patients (6%) were found to be unresectable. Distant metastases were classified into pulmonary and extrapulmonary. Overall survival (OS), disease-specific survival (DSS), and locoregional recurrence-free survival were calculated by the Kaplan-Meier method. Factors predictive of the outcome were determined by univariate and multivariate analyses. Results: Thirty-nine patients (75%) were diagnosed with pulmonary metastases alone and 13 (25%) with extrapulmonary metastases. The sites of extrapulmonary metastases were bone in nine, mediastinum in one, pyriform sinus in one and skin in one, and one patient had synchronous lung, bone, and intracerebral metastases. After thyroid surgery, 47 patients (90%) were treated with RAI alone, and 2 patients had external beam radiation in addition to RAI. With a median follow-up after surgery of 78.5 months, the 5-year OS and DSS were 65% and 68%, respectively. Twenty-nine patients (56%) died during follow-up, of whom 24 (46%) died of thyroid cancer. Six patients (12%) developed recurrent disease in the lateral neck, and three patients (6%) developed recurrence in the thyroid bed. Over 45 years, follicular pathology and extrapulmonary metastases were predictive of lower 5-year DSS (56% vs. 100%, p<0.001; 50% vs. 70%, p=0.004; and 46% vs. 75%, p=0.013, respectively). Conclusion: Approximately half of patients with WDTC presenting with distant metastases die of disease within 5 years of initial diagnosis despite thyroid surgery and RAI. Age over 45 years, extrapulmonary metastases, and follicular pathology were significant predictors of the poor outcome. [ABSTRACT FROM AUTHOR]

Background: There remains controversy over the type of surgery appropriate for T1T2N0 well differentiated thyroid cancers (WDTC). Current guidelines recommend total thyroidectomy for all but the smallest lesions, despite previous evidence from large institutions suggesting that lobectomy provides similar excellent results. The objective of this study was to report our experience of T1T2N0 WDTC managed by either thyroid lobectomy or total thyroidectomy. Methods: Eight hundred eighty-nine patients with pT1T2 intrathyroid cancers treated surgically between 1986 and 2005 were identified from a database of 1810 patients with WDTC. Total thyroidectomy was carried out in 528 (59%) and thyroid lobectomy in 361 (41%) patients. Overall survival (OS), disease-specific survival (DSS) and recurrence-free survival (RFS) were determined by the Kaplan-Meier method. Factors predictive of outcome by univariate and multivariate analysis were determined using the log rank test and Cox proportional hazards method respectively. Results: With a median follow-up of 99 months, the 10-yr OS, DSS, and RFS for all patients were 92%, 99%, and 98% respectively. Univariate analysis showed no significant difference in OS by extent of surgical resection. Multivariate analysis showed that age over 45 yr and male gender were independent predictors for poorer OS, whereas T stage and type of surgery were not. Comparison of the thyroid lobectomy group and the total thyroidectomy group showed no difference in local recurrence (0% for both) or regional recurrence (0% vs 0.8%, P = .96). Conclusion: Patients with pT1T2 N0 WDTC can be safely managed by thyroid lobectomy alone. [ABSTRACT FROM AUTHOR]

Background. There is an increasing awareness of the association of papillary thyroid carcinoma and familial adenomatous polyposis (FAP). Although the incidence is rare, most tend to occur in women. Several authors have described a distinctive histologic variant of papillary thyroid carcinoma, the cribriform-morular variant, which is associated with FAP but also may be encountered in patients with non-FAP. This diagnosis may precede the symptoms of colorectal polyposis. Methods. A healthy 36-year-old woman was seen with a left thyroid nodule, and a 34-year-old woman with FAP was seen with a right thyroid nodule; both masses were suspicious for papillary thyroid carcinoma. Both patients underwent total thyroidectomy. Results. Pathologic examination of both specimens revealed papillary thyroid carcinoma, cribriform-morular variant. The first patient subsequently underwent colonoscopy, which was negative for polyposis. Conclusions. Patients diagnosed with the cribriform-morular variant of papillary thyroid cancer should be screened for the presence of FAP. © 2006 Wiley Periodicals, Inc. Head Neck28: 471–476, 2006 [ABSTRACT FROM AUTHOR]