Search

ObjectiveCancer patients and survivors may be disproportionately affected by COVID-19. We sought to determine the effects of the pandemic on thyroid cancer survivors' health care interactions and quality of life.MethodsAn anonymous survey including questions about COVID-19 and the Patient-Reported Outcomes Measurement Information System profile (PROMIS-29, version 2.0) was hosted on the Thyroid Cancer Survivors' Association, Inc website. PROMIS scores were compared to previously published data. Factors associated with greater anxiety were evaluated with univariable and multivariable logistic regression.ResultsFrom May 6, 2020, to October 8, 2020, 413 participants consented to take the survey; 378 (92%) met the inclusion criteria: diagnosed with thyroid cancer or noninvasive follicular neoplasm with papillary-like nuclear features, located within the United States, and completed all sections of the survey. The mean age was 53 years, 89% were women, and 74% had papillary thyroid cancer. Most respondents agreed/strongly agreed (83%) that their lives were very different during the COVID-19 pandemic, as were their interactions with doctors (79%). A minority (43%) were satisfied with the information from their doctor regarding COVID-19 changes. Compared to pre-COVID-19, PROMIS scores were higher for anxiety (57.8 vs 56.5; P < .05) and lower for the ability to participate in social activities (46.2 vs 48.1; P < .01), fatigue (55.8 vs 57.9; P < .01), and sleep disturbance (54.7 vs 56.1; P < .01). After adjusting for confounders, higher anxiety was associated with younger age (P < .01) and change in treatment plan (P = .04).ConclusionDuring the COVID-19 pandemic, thyroid cancer survivors reported increased anxiety compared to a pre-COVID cohort. To deliver comprehensive care, providers must better understand patient concerns and improve communication about potential changes to treatment plans.

BackgroundGuidelines recommend screening for primary aldosteronism in patients diagnosed with hypertension and obstructive sleep apnea. Recent studies have shown that adherence to these recommendations is extremely low. It has been suggested that cost is a barrier to implementation. No analysis has been done to rigorously evaluate the cost-effectiveness of widespread implementation of these guidelines.MethodsWe constructed a decision-analytic model to evaluate screening of the hypertensive obstructive sleep apnea population for primary aldosteronism as per guideline recommendations in comparison with current rates of screening. Probabilities, utility values, and costs were identified in the literature. Threshold and sensitivity analyses assessed robustness of the model. Costs were represented in 2020 US dollars and health outcomes in quality-adjusted life-years. The model assumed a societal perspective with a lifetime time horizon.ResultsScreening per guideline recommendations had an expected cost of $47,016 and 35.27 quality-adjusted life-years. Continuing at current rates of screening had an expected cost of $48,350 and 34.86 quality-adjusted life-years. Screening was dominant, as it was both less costly and more effective. These results were robust to sensitivity analysis of disease prevalence, test sensitivity, patient age, and expected outcome of medical or surgical treatment of primary aldosteronism. The screening strategy remained cost-effective even if screening were conservatively presumed to identify only 3% of new primary aldosteronism cases.ConclusionsFor patients with hypertension and obstructive sleep apnea, rigorous screening for primary aldosteronism is cost-saving due to cardiovascular risk averted. Cost should not be a barrier to improving primary aldosteronism screening adherence.

BackgroundResistant hypertension is common in patients with primary aldosteronism and in those with obstructive sleep apnea. Primary aldosteronism treatment improves sleep apnea. Despite Endocrine Society guidelines' inclusion of sleep apnea and hypertension co-diagnosis as a primary aldosteronism screening indication, the state of screening implementation is unknown.MethodsAll hypertensive adult patients with obstructive sleep apnea (n = 4751) at one institution between 2012 and 2020 were compared with a control cohort without sleep apnea (n = 117,815). We compared the association of primary aldosteronism diagnoses, risk factors, and screening between both groups. Patients were considered to have screening if they had a primary aldosteronism diagnosis or serum aldosterone or plasma renin activity evaluation.ResultsObstructive sleep apnea patients were predominantly men and had higher body mass index. On multivariable analysis, hypertensive sleep apnea patients had higher odds of drug-resistant hypertension (odds ratio [OR] 2.70; P < .001) and hypokalemia (OR 1.26; P < .001) independent of body mass index, sex, and number of antihypertensive medications. Overall, sleep apnea patients were more likely to be screened for primary aldosteronism (OR 1.45; P < .001); however, few patients underwent screening whether they had sleep apnea or not (pre-guideline publication 7.8% vs 4.6%; post-guidelines 3.6% vs 4.6%; P < .01). Screening among eligible sleep apnea patients remained low prior to and after guideline publication (4.4% vs 3.4%).ConclusionsObstructive sleep apnea is associated with primary aldosteronism risk factors without formal diagnosis, suggesting screening underutilization and underdiagnosis. Strategies are needed to increase screening adherence, as patients may benefit from treatment of concomitant primary aldosteronism to reduce sleep apnea severity and its associated cardiopulmonary morbidity.

ImportanceTransoral endocrine surgery (TES) allows thyroid and parathyroid operations to be performed without leaving any visible scar on the body. Controversy regarding the value of TES remains, in part owing to the common belief that TES is only applicable to a small, select group of patients. Knowledge of the overall applicability of these procedures is essential to understand the operation, as well as to decide the amount of effort and resources that should be allocated to further study the safety, efficacy, and value of these operations.ObjectiveTo determine what percentage of US patients undergoing thyroid and parathyroid surgery are eligible for TES using currently accepted exclusion criteria.Design, setting, and participantsCross-sectional study of 1000 consecutive thyroid and parathyroid operations (with or without neck dissection) performed between July 1, 2015, and July 1, 2018, at 3 high-volume academic US thyroid- and parathyroid-focused surgical practices (2 general surgery, 1 otolaryngology-head and neck endocrine surgery). Eligibility for TES was determined by retrospectively applying previously published exclusion criteria to the cases.Main outcomes and measuresThe primary outcome was the percentage of thyroid and parathyroid cases eligible for TES. Secondary outcomes were a subgroup analysis of the percentage of specific types of cases eligible and the reasons for ineligibility.ResultsThe mean (SD) age of the 1000 surgical patients was 53 (15) years, mean (SD) body mass index (calculated as weight in kilograms divided by height in meters squared) was 29 (7), and 747 (75.0%) of the patients were women. Five hundred fifty-eight (55.8%) of the patients were eligible for TES. Most patients with thyroid nodules with cytologically indeterminate behavior (165 of 217 [76.0%]), benign thyroid conditions (166 of 240 [69.2%]), and primary hyperparathyroidism (158 of 273 [57.9%]) were eligible for TES, but only 67 of 231 (29.0%) of patients with thyroid cancer were eligible. Among all 1000 cases reviewed, previous neck operation (97 of 441 [22.0%]), nonlocalized primary hyperparathyroidism (78 of 441 [17.7%]), and need for neck dissection (66 of 441 [15.0%]) were the most common reasons for ineligibility.Conclusions and relevanceMore than half of all patients undergoing thyroid and parathyroid surgery in this study were eligible for TES. This broad applicability suggests that a prospective multicenter trial is reasonable to definitively study the safety, outcomes, and cost of TES.

BackgroundMinimally invasive and remote access thyroid surgery has been evolving with the transoral endoscopic thyroidectomy vestibular approach (TOETVA) emerging as a true "scarless" thyroidectomy. In this study, we describe a hybrid transoral and submental thyroidectomy (TOaST) technique for thyroid lobectomy.Materials and methodsA TOaST right thyroid lobectomy was performed for a 4 cm cytologically benign right thyroid nodule. Initial incision was made in the submental region with two additional 5 mm lateral ports inserted transorally. Right thyroid lobectomy proceeded via standard TOETVA with intact specimen extraction via the submental incision.ResultsThe patient was discharged home on postoperative day 1. Final pathology showed a 4.2 cm follicular adenoma. Cosmetic results and patient satisfaction were excellent.DiscussionThis is the first reported case of a hybrid TOaST technique. It aims to maintain the principles and advantages of TOETVA while addressing its limitations related to large tumor extraction, mental nerve injury, and chin sensory changes. The shorter distance of dissection required may reduce postoperative pain. This approach may expand the indications for transoral thyroidectomy while maintaining excellent cosmetic outcomes.

ImportanceLaparoscopic adrenalectomy is the gold standard for most adrenal disorders and its frequency in the United States is increasing. While national and administrative databases can adjust for patient factors, comorbidities, and institutional variations, granular disease-specific data that may significantly influence the incidence of perioperative complications and length of stay (LOS) are lacking.ObjectiveTo investigate factors associated with perioperative complications and LOS after laparoscopic adrenalectomy.Design, setting, and participantsThis cohort study was carried out at a single academic medical center, with all patients who underwent laparoscopic adrenalectomy between 1993 and 2017 by the endocrine surgery department. Multivariable linear and logistic regression were used to obtain adjusted odds ratios (ORs).Main outcomes and measuresThe primary outcome was perioperative complications with a Dindo-Clavien grade of 2 or more. The secondary outcome was prolonged length of stay, defined as a stay longer than the 75th percentile of the overall cohort.ResultsWe identified 640 patients who underwent 653 laparoscopic adrenalectomies, of whom 370 (56.7%) were female. The median age was 51 (range, 5-88) years. A total of 76 complications with a Dindo-Clavien grade of 2 or more occurred in 55 patients (8.4%), with postoperative mortality in 2 patients (0.3%). The median hospital length of stay was 1 day (range, 0-32 days). Factors independently associated with increased complications were American Society of Anesthesiologists class 3 or 4 (OR, 2.78 [95% CI, 1.39-5.55]; P

BackgroundPrimary hyperparathyroidism (PHPT) is a common endocrine disorder that predominantly affects patients >60 and is increasing in prevalence. Identifying risk factors for poor outcomes after parathyroidectomy in older adults will help tailor operative decision making. The impact of frailty on surgical outcomes in parathyroidectomy has not been established.MethodsWe performed a retrospective review of patients ≥40 years who underwent parathyroidectomy in the 2005-2010 ACS NSQIP. Frailty was assessed using the modified frailty index (mFI). Multivariable regression was used to determine the association of frailty with 30-day complications, length of stay (LOS), and reoperation.ResultsWe identified 13,123 patients ≥40 who underwent parathyroidectomy for PHPT. The majority of patients were not frail, with 80% with a low NSQIP mFI score (0-1 frailty traits), 19% with an intermediate mFI score (2-3), and 0.9% with a high mFI score (≥4). Overall 30-day complications were rare, occurring in 141 (1.1%) patients. Increasing frailty was associated with an increased risk of complications with adjusted odds ratios (ORs) of 1.76 (95% CI 1.20-2.59; p = 0.004) for intermediate and 8.43 (95% CI 4.33-16.41; p

ImportanceUse of next-generation sequencing of RNA and machine learning algorithms can classify the risk of malignancy in cytologically indeterminate thyroid nodules to limit unnecessary diagnostic surgery.ObjectiveTo measure the performance of a genomic sequencing classifier for cytologically indeterminate thyroid nodules.Design, setting, and participantsA blinded validation study was conducted on a set of cytologically indeterminate thyroid nodules collected by fine-needle aspiration biopsy between June 2009 and December 2010 from 49 academic and community centers in the United States. All patients underwent surgery without genomic information and were assigned a histopathology diagnosis by an expert panel blinded to all genomic information. There were 210 potentially eligible thyroid biopsy samples with Bethesda III or IV indeterminate cytopathology that constituted a cohort previously used to validate the gene expression classifier. Of these, 191 samples (91.0%) had adequate residual RNA for validation of the genomic sequencing classifier. Algorithm development and independent validation occurred between August 2016 and May 2017.ExposuresThyroid nodule surgical histopathology diagnosis by an expert panel blinded to all genomic data.Main outcomes and measuresThe primary end point was measurement of genomic sequencing classifier sensitivity, specificity, and negative and positive predictive values in biopsies from Bethesda III and IV nodules. The secondary end point was measurement of classifier performance in biopsies from Bethesda II, V, and VI nodules.ResultsOf the 183 included patients, 142 (77.6%) were women, and the mean (range) age was 51.7 (22.0-85.0) years. The genomic sequencing classifier had a sensitivity of 91% (95% CI, 79-98) and a specificity of 68% (95% CI, 60-76). At 24% cancer prevalence, the negative predictive value was 96% (95% CI, 90-99) and the positive predictive value was 47% (95% CI, 36-58).Conclusions and relevanceThe genomic sequencing classifier demonstrates high sensitivity and accuracy for identifying benign nodules. Its 36% increase in specificity compared with the gene expression classifier potentially increases the number of patients with benign nodules who can safely avoid unnecessary diagnostic surgery.

Genetic testing for pheochromocytoma and paraganglioma allows for early detection of hereditary syndromes and enables close follow-up of high-risk patient. We investigated the trends in genetic testing among patients at a high-volume referral center and evaluated the prevalence of pheochromocytomas and paragangliomas.We reviewed the charts of 129 patients who underwent adrenalectomy for pheochromocytoma and paraganglioma between January 2000 and July 2015. To evaluate for trends in genetic testing, patients were divided by year of diagnosis: 2000-2005 (group 1, n = 35), 2006-2010 (group 2, n = 44), and 2011-2015 (group 3, n = 50).Among 129 patients the mean age was 47 years and 56% were women. Groups 2 and 3 were more frequently referred for genetic consultation than group 1, 73%, and 94% versus 26% (P

BACKGROUND:Papillary thyroid carcinoma with squamous differentiation (PTC-SD) is a poorly understood pathologic finding of unknown clinical significance. Selected case reports have suggested that PTC-SD is an aggressive tumor with a poor prognosis. Here we present the largest case series of PTC-SD reported in the United States. MATERIALS AND METHODS:The cancer registry at our tertiary care referral center was reviewed to identify all patients from 1995-2015 who had been diagnosed with PTC-SD on initial total thyroidectomy or lymph node dissection for recurrent disease. All cases were reviewed by an endocrine pathologist to confirm the diagnosis. Patient demographic, pathology, and outcomes data were collected and reviewed. RESULTS:During the study period, ten patients were diagnosed with PTC-SD, six in the primary tumor at the time of initial surgery, and four in lymph node metastases during surgery for recurrent disease. The median age at diagnosis was 56 y and half of the patients were male. Aggressive features such as multifocality (67%), extrathyroidal extension (67%), positive margin (89%), lymph node metastases (80%), and extranodal extension (60%) were far more prominent than is typically seen in classic PTC. Long-term follow-up (median 56.5 mo) demonstrated high rates of locoregional recurrence (60%), pulmonary metastases (30%), and mortality (10%). CONCLUSIONS:Squamous differentiation is a rare finding in PTC that is associated with aggressive pathologic features and poor long-term outcomes. This phenomenon may represent a step in progression toward dedifferentiation; thus, patients with PTC-SD should have close, life-long surveillance and should be treated according to evidence-based guidelines for high-risk thyroid cancers.

ImportanceFrailty is a measure of decreased physiological reserve that is associated with morbidity and mortality in major elective and emergency general surgery operations, independent of chronological age. To date, the association of frailty with outcomes in ambulatory general surgery has not been established.ObjectiveTo determine the association between frailty and perioperative morbidity in patients undergoing ambulatory general surgery operations.Design, setting, and participantsA retrospective cohort study was conducted of 140 828 patients older than 40 years of age from the 2007-2010 American College of Surgeons National Surgical Quality Improvement Program Participant Use File who underwent ambulatory and 23-hour-stay hernia, breast, thyroid, or parathyroid surgery. Data analysis was performed from August 18, 2016, to June 21, 2017.Main outcomes and measuresThe association between the National Surgical Quality Improvement Program modified frailty index and perioperative morbidity was determined via multivariable logistic regression with random-effects modeling to control for clustering within Current Procedural Terminology codes.ResultsA total of 140 828 patients (80 147 women and 60 681 men; mean [SD] age, 59.3 [12.0] years) underwent ambulatory hernia (n = 71 455), breast (n = 51 267), thyroid, or parathyroid surgery (n = 18 106). Of these patients, 2457 (1.7%) experienced any type of perioperative complication and 971 (0.7%) experienced serious perioperative complications. An increasing modified frailty index was associated with a stepwise increase in the incidence of complications. In multivariable analysis adjusting for age, sex, race/ethnicity, anesthesia type, tobacco use, renal failure, corticosteroid use, and clustering by Current Procedural Terminology codes, an intermediate modified frailty index score (0.18-0.35, corresponding to 2-3 frailty traits) was associated with statistically significant odds ratios of 1.70 (95% CI, 1.54-1.88; P

BACKGROUND:The 7th AJCC T-stage system for adrenocortical carcinoma (ACC), based on size and extra-adrenal invasion, does not adequately stratify patients by survival. Lymphovascular invasion (LVI) is a known poor prognostic factor. We propose a novel T-stage system that incorporates LVI to better risk-stratify patients undergoing resection for ACC. METHOD:Patients undergoing curative-intent resections for ACC from 1993 to 2014 at 13 institutions comprising the US ACC Group were included. Primary outcome was disease-specific survival (DSS). RESULTS:Of the 265 patients with ACC, 149 were included for analysis. The current T-stage system failed to differentiate patients with T2 versus T3 disease (p = 0.10). Presence of LVI was associated with worse DSS versus no LVI (36 mo vs. 168 mo; p = 0.001). After accounting for the individual components of the current T-stage system (size, extra-adrenal invasion), LVI remained a poor prognostic factor on multivariable analysis (hazard ratio 2.14, 95% confidence interval 1.05-4.38, p = 0.04). LVI positivity further stratified patients with T2 and T3 disease (T2: 37 mo vs. median not reached; T3: 36 mo vs. 96 mo; p = 0.03) but did not influence survival in patients with T1 or T4 disease. By incorporating LVI, a new T-stage classification system was created: [T1: ≤ 5 cm, (-)local invasion, (+/-)LVI; T2: > 5 cm, (-)local invasion, (-)LVI OR any size, (+)local invasion, (-)LVI; T3: > 5 cm, (-)local invasion, (+)LVI OR any size, (+)local invasion, (+)LVI; T4: any size, (+)adjacent organ invasion, (+/-)LVI]. Each progressive new T-stage group was associated with worse median DSS (T1: 167 mo; T2: 96 mo; T3: 37 mo; T4: 15 mo; p

Hypoparathyroidism is a potential outcome of anterior neck surgery. Commonly it is managed by calcium and vitamin D supplementation in large doses, with attendant side effects. A recombinant human parathyroid hormone (rhPTH) is now available in the USA, offering a potentially more effective treatment. No cost-effectiveness model investigating this new medication versus standard care has yet been published.We constructed a decision analytic model comparing usual care versus rhPTH treatment for postsurgical hypoparathyroidism. Threshold and sensitivity analyses on key parameters were conducted to assess robustness of the model. Costs and health outcomes were represented in US dollars and quality-adjusted life-years (QALYs).The rhPTH strategy was both more costly and more effective than the usual care (UC) strategy. In the base case, UC cost $37,196 and provided 7.54 QALYs. The rhPTH strategy cost $777,224 and provided 8.46 QALYs for an incremental cost-effectiveness ratio of $804,378/QALY. As this was above our willingness-to-pay of $100,000, treatment with rhPTH was not considered cost-effective. The model was robust to all other parameters.To our knowledge, this is the first formal cost-effectiveness analysis of rhPTH in comparison with UC. Our model suggests that although the new treatment is slightly more effective than UC, the modest gain in quality of life for patients who are reasonably well-managed by UC does not justify the cost. However, consideration must be given to rhPTH for patients who have failed UC, as the expenditure may be justified in that context.

Background and objectivesPathological examination occasionally reveals incidental central lymph nodes metastasis (iLNM) after thyroidectomy for patients with papillary thyroid cancer (PTC) who did not undergo compartment-orientated lymphadenectomy. We aimed to investigate the risk of recurrence for patients with iLNM.MethodsWe conducted a retrospective review of all patients undergoing total thyroidectomy for PTC (January 2000 to January 2010). Patients with distant metastases, central- or lateral neck dissection and pre-operative suspicious lymph nodes (by ultrasound or clinical examination) were excluded. The association between iLNM and recurrent disease was investigated using Kaplan-Meier survival estimates and Cox proportional hazards analysis.Results225/1000 patients had incidental nodes after total thyroidectomy for PTC. 183 were node-negative and 42 had iLNM. Mean age was 46 years and 201 (89%) were women. Mean number of resected nodes was 2.3. Disease recurred in 8/183 (4.4%) of patients with N0 versus 7/42 (17%) with iLNM. After adjusting for other factors, iLNM was independently associated with recurrent disease (hazard ratio = 4.01 [95% CI 1.21-13.3]).ConclusionsPositive incidental lymph nodes are independently associated with recurrent disease in patients with PTC. These patients should therefore be monitored more carefully.

Purpose To investigate the performance of flourine 18 (18F) fluorocholine (FCH) positron emission tomography (PET)/magnetic resonance (MR) imaging in patients with hyperparathyroidism and nonlocalized disease who have negative or inconclusive results at ultrasonography (US) and technetium 99m (99mTc) sestamibi scintigraphy. Materials and Methods This study was approved by the institutional review board. Between May and December 2015, 10 patients (mean age, 70.4 years; range, 58-82 years) with biochemical primary hyperparathyroidism and inconclusive results at US and 99mTc sestamibi scintigraphy were prospectively enrolled. All patients gave informed consent. Directly after administration of 3 MBq/kg of FCH, PET imaging was performed, followed by T1- and T2-weighted MR imaging before and after gadolinium enhancement. Intraoperative localization and histologic results were the reference standard for calculating sensitivity and positive predictive value. The Wilcoxon rank test was used to calculate the mean difference in maximum standardized uptake value (SUVmax) between abnormal parathyroid uptake and physiologic thyroid uptake. The Wilcoxon rank-sum test was performed. Results MR imaging alone showed true-positive lesions in five patients and a false-positive lesion in one patient. FCH PET/MR imaging allowed correct localization of nine of 10 adenomas (90% sensitivity), without any false-positive results (100% positive predictive value). One patient had four-gland hyperplasia, of which three hyperplastic glands were not localized. The median SUVmax of the nine preoperatively identified adenomas was 4.9 (interquartile range, 2.45-7.35), which was significantly higher than the SUV, 2.7 (interquartile range, 1.6-3.8), of the thyroid (P = .008). Conclusion FCH PET/MR imaging allowed localization of adenomas with high accuracy when conventional imaging results were inconclusive and provided detailed anatomic information. More patients must be examined to confirm our initial results, and the accuracy of FCH PET/MR imaging for localization of glands in patients with four-gland hyperplasia remains to be investigated. © RSNA, 2017.

Perioperative blood transfusion is associated with decreased survival in pancreatic, gastric, and liver cancer. The effect of transfusion in adrenocortical carcinoma (ACC) has not been studied. Patients with available transfusion data undergoing curative-intent resection of ACC from 1993 to 2014 at 13 institutions comprising the United States Adrenocortical Carcinoma Group were included. Factors associated with blood transfusion were determined. Primary and secondary end points were recurrence-free survival (RFS) and overall survival (OS), respectively. Out of 265 patients, 149 were included for analysis. Out of these, 57 patients (38.3%) received perioperative transfusions. Compared to nontransfused patients, transfused patients more commonly had stage 4 disease (46% vs 24%, P = 0.01), larger tumors (15.8 vs 10.2 cm, P < 0.001), inferior vena cava involvement (24.6% vs 5.4%, P = 0.002), additional organ resection (78.9% vs 36.3%, P < 0.001), and major complications (29% vs 2%, P < 0.001). Transfusion was associated with decreased RFS (8.9 vs 24.7 months, P = 0.006) and OS (22.8 vs 91.0 months, P < 0.001). On univariate Cox regression, transfusion, stage IV, hormonal hypersecretion, and adjuvant therapy were associated with decreased RFS. On multivariable analysis, only transfusion [hazard ratio (HR) = 1.7, 95% confidence interval (CI) =1.0-2.9, P = 0.04], stage IV (HR = 3.2, 95% CI = 1.7-5.9, P < 0.001), and hormonal hypersecretion (HR = 2.6, 95% CI = 1.5-4.2, P < 0.001) were associated with worse RFS. When applying this model to OS, similar associations were seen (transfusion HR = 2.0, 95% CI = 1.1-3.8, P = 0.02; stage 4 HR = 6.2, 95% CI = 3.1-12.4, P < 0.001; hormonal hypersecretion HR = 3.5, 95% CI = 1.9-6.4, P < 0.001). There was no difference in outcomes between patients who received 1 to 2 units versus >2 units of packed red blood cells in median RFS (8.9 vs 8.4 months, P = 0.95) or OS (26.5 vs 18.6 months, P = 0.63). Perioperative transfusion is associated with earlier recurrence and decreased survival after curative-intent resection of ACC. Strategies and protocols to minimize blood transfusion should be developed and followed.

BackgroundCatecholamine excess in patients with pheochromocytoma often results in impaired glucose tolerance, leading to diabetes mellitus. Little data are available on the long-term effect of surgery on diabetes.ObjectiveThe primary aim of this study was to determine the likelihood of diabetes cure after surgery, while secondary objectives were to determine risk factors for development of diabetes preoperatively and persistence of diabetes postoperatively.MethodsAll patients undergoing surgery for pheochromocytoma from 1996 to 2015 were retrospectively reviewed to identify those with a preoperative diagnosis of diabetes. Demographic and diabetes-specific data were collected. Median follow-up was 52.1 months.ResultsOverall, 153 patients underwent surgery. Diabetes was seen in 36 (23.4%) patients. Eight patients met the exclusion criteria and were removed from the final analysis, while 22 (78.6%) patients had complete resolution of diabetes. Four patients remained on medication with improved control. Overall, 93.0% of patients had improvement of their diabetes; two patients did not improve. Patients with large, symptomatic tumors were more likely to develop preoperative diabetes, and diabetes was more likely to persist in patients who had an elevated body mass index (BMI).ConclusionsDiabetes was found concurrently with pheochromocytoma in 23% of patients, more often in those with large, symptomatic tumors. The majority of patients had long-term resolution of diabetes after successful resection; however, some patients may continue to require treatment of diabetes after operation, especially those with a higher BMI.

PurposeTo 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 methodsWe 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.ResultsThirty-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%).ConclusionCT 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 objectivesWe investigated the rate, stage, and prognosis of thyroid cancer in patients after solid-organ transplantations, and compared this to the general population.MethodsWe 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.ResultsA 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.ConclusionRate 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 and objectivesMinimally invasive surgery for adrenocortical carcinoma (ACC) is controversial. We sought to evaluate the perioperative and long-term outcomes following minimally invasive (MIS) and open resection (OA) of ACC in patients treated with curative intent surgery.MethodsRetrospective data from patients who underwent adrenalectomy for primary ACC at 13 tertiary care cancer centers were analyzed, including demographics, clinicopathological, and operative outcomes. Outcomes following MIS were compared to OA.ResultsA total of 201 patients were evaluated including 47 MIS and 154 OA. There was no difference in utilization of MIS approach among institutions (p = 0.24) or 30-day morbidity (29.3 %, MIS, vs. 30.9 %, OA; p = 0.839). The only preoperatively determined predictor for MIS was smaller tumor size (p

BackgroundThe 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.MethodsWe 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.ResultsA 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.ConclusionDespite 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.

BackgroundThe management of low-risk micropapillary thyroid cancer

ObjectiveTo evaluate conditional disease-free survival (CDFS) for patients who underwent curative intent surgery for adrenocortical carcinoma (ACC).BackgroundACC is a rare but aggressive tumor. Survival estimates are usually reported as survival from the time of surgery. CDFS estimates may be more clinically relevant by accounting for the changing likelihood of disease-free survival (DFS) according to time elapsed after surgery.MethodsCDFS was assessed using a multi-institutional cohort of patients. Cox proportional hazards models were used to evaluate factors associated with DFS. Three-year CDFS (CDFS3) estimates at "x" year after surgery were calculated as follows: CDFS3 = DFS(x+3)/DFS(x).ResultsOne hundred ninety-two patients were included in the study cohort; median patient age was 52 years. On presentation, 36% of patients had a functional tumor and median size was 11.5 cm. Most patients underwent R0 resection (75%) and 9% had N1 disease. Overall 1-, 3-, and 5-year DFS was 59%, 34%, and 22%, respectively. Using CDFS estimates, the probability of remaining disease free for an additional 3 years given that the patient had survived without disease at 1, 3, and 5 years, was 43%, 53%, and 70%, respectively. Patients with less favorable prognosis at baseline demonstrated the greatest increase in CDFS3 over time (eg, capsular invasion: 28%-88%, Δ60% vs no capsular invasion: 51%-87%, Δ36%).ConclusionsDFS estimates for patients with ACC improved dramatically over time, in particular among patients with initial worse prognoses. CDFS estimates may provide more clinically relevant information about the changing likelihood of DFS over time.

BackgroundPrimary 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.MethodsWe 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.ResultsEight 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).ConclusionsSome 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.

BackgroundAdrenocortical carcinoma (ACC) is an aggressive malignancy typically resistant to chemotherapy and radiation. Surgery, even in the setting of locally recurrent or metastatic disease, remains the only potentially curative option. However, the subset of patients who will benefit from repeat resection in this setting remains ill defined. The objective of this study was to propose a prognostic clinical score that facilitates selection of patients for repeat resection of recurrent ACC.Study designPatients who underwent curative-intent repeat resection for recurrent ACC at 1 of 13 academic medical centers participating in the US ACC Study Group were identified. End points included morbidity, mortality, and overall survival.ResultsFifty-six patients underwent repeat curative-intent resection for recurrent ACC (representing 21% of 265 patients who underwent resection for primary ACC) from 1997 to 2014. Median age was 52 years. Sites of resected recurrence included locoregional only (54%), lung only (14%), liver only (12%), combined locoregional and lung (4%), combined liver and lung (4%), and other distant sites (12%). Thirty-day morbidity and mortality rates were 40% and 5.4%, respectively. Cox regression analysis revealed that the presence of multifocal recurrence, disease-free interval 12 months, and locoregional or pulmonary recurrence.

BackgroundAdrenocortical carcinoma (ACC) is a rare and aggressive malignancy with limited therapeutic options beyond surgical resection. The characteristics of actual long-term survivors following surgical resection for ACC have not been previously reported.MethodPatients who underwent resection for ACC at one of 13 academic institutions participating in the US Adrenocortical Carcinoma Group from 1993 to 2014 were analyzed. Patients were stratified into four groups: early mortality (died within 2 years), late mortality (died within 2-5 years), actual 5-year survivor (survived at least 5 years), and actual 10-year survivor (survived at least 10 years). Patients with less than 5 years of follow-up were excluded.ResultsAmong the 180 patients available for analysis, there were 49 actual 5-year survivors (27%) and 12 actual 10-year survivors (7%). Patients who experienced early mortality had higher rates of cortisol-secreting tumors, nodal metastasis, synchronous distant metastasis, and R1 or R2 resections (all P

BackgroundThe 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.MethodsThis 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.ResultsIP occurred in 286 (16.2 %) of thyroidectomies. Risk factors for IP were: malignancy, neck dissection, and lymph node metastases (p = 0.005,

BackgroundPreoperative 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.MethodsAll 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.ResultsA 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%.ConclusionTechnologic 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.

BackgroundThe 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.MethodsPatients 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.ResultsOf 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.ConclusionsNearly 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.

BackgroundWe sought to define the impact of cortisol-secreting status on outcomes after surgical resection of adrenocortical carcinoma (ACC).MethodsThe U.S ACC group database was queried to identify patients who underwent ACC resection between 1993 and 2014. The short-term and long-term outcomes were assessed.ResultsThe incidence of all functional and cortisol-secreting tumors was 40.6% and 22.6%, respectively. On multivariable analysis, cortisol secretion remained associated with an increased risk of postoperative complications (odds ratio = 2.25, 95 % confidence interval = 1.04 to 4.88; P = .04). At a median follow-up of 17.6 months, 118 patients (50.4%) had developed a recurrence. On multivariable analysis, after adjusting for patient and disease-related factors cortisol secretion independently predicted shorter recurrence-free survival (Hazard ratio = 2.05, 95% confidence interval = 1.16 to 3.60; P = .01).ConclusionsCortisol secretion was associated with an increased risk of postoperative morbidity. Recurrence remains high among patients with ACC after surgery; cortisol secretion was independently associated with a shorter recurrence-free survival. Tailoring postoperative surveillance of ACC patients based on their cortisol secreting status may be important.

BackgroundIncomplete 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.MethodsWe 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.ResultsOf 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.ConclusionsA 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.

Laparoscopic abdominal surgery may prove difficult in patients who have undergone previous abdominal procedures. No reports in the medical literature have presented an aborted laparoscopic procedure for failed pneumoperitoneum following autologous flap-based breast reconstruction.A 55-year-old woman presented with recurrent invasive lobular carcinoma of the right breast as well as a history of ductal carcinoma in situ of the left breast. The patient desired to proceed with bilateral skin- and nipple-sparing mastectomies with right axillary lymph node biopsy, followed by immediate bilateral autologous deep inferior epigastric perforator (DIEP) flap-based breast reconstruction. Preoperatively, a computerized tomography angiogram was obtained for reconstructive preparation, which revealed a left adrenal mass. Ensuing work-up diagnosed a pheochromocytoma. Given the concern for breast cancer progression, the patient elected to proceed first with breast cancer surgery and reconstruction prior to addressing the adrenal tumor. Subsequently, 3 months later the patient was brought to the operating room for a laparoscopic left adrenalectomy for the pheochromocytoma. With complete pharmacologic abdominal relaxation, the abdomen proved too tight to accommodate sufficient pneumoperitoneum and the laparoscopy was aborted. The patient was evaluated in the outpatient setting for assessment of abdominal wall compliance at regular intervals. Five months later, the patient was taken back to the operating room where pneumoperitoneum was established without difficulty and the laparoscopic left adrenalectomy was performed without complications.Pneumoperitoneum for laparoscopic surgery subsequent to autologous DIEP flap-based breast reconstruction may prove difficult as a result of loss of abdominal wall compliance. Prior to performing laparoscopy in such patients, surgeons should consider the details of the patient's previous reconstructive procedure and assess potential risk factors for difficulty with insufflation. Lastly, careful abdominal examination should be performed to indicate whether laparoscopy for elective procedures should be delayed until abdominal wall compliance normalizes.

BackgroundCurrent treatment guidelines recommend adjuvant mitotane after resection of adrenocortical carcinoma with high-risk features (eg, tumor rupture, positive margins, positive lymph nodes, high grade, elevated mitotic index, and advanced stage). Limited data exist on the outcomes associated with these practice guidelines.Study designPatients who underwent resection of adrenocortical carcinoma from 1993 to 2014 at the 13 academic institutions of the US Adrenocortical Carcinoma Group were included. Factors associated with mitotane administration were determined. Primary end points were recurrence-free survival (RFS) and overall survival (OS).ResultsOf 207 patients, 88 (43%) received adjuvant mitotane. Receipt of mitotane was associated with hormonal secretion (58% vs 32%; p = 0.001), advanced TNM stage (stage IV: 42% vs 23%; p = 0.021), adjuvant chemotherapy (37% vs 5%; p < 0.001), and adjuvant radiation (17% vs 5%; p = 0.01), but was not associated with tumor rupture, margin status, or N-stage. Median follow-up was 44 months. Adjuvant mitotane was associated with decreased RFS (10.0 vs 27.9 months; p = 0.007) and OS (31.7 vs 58.9 months; p = 0.006). On multivariable analysis, mitotane was not independently associated with RFS or OS, and margin status, advanced TNM stage, and receipt of chemotherapy were associated with survival. After excluding all patients who received chemotherapy, adjuvant mitotane remained associated with decreased RFS and similar OS; multivariable analyses again showed no association with recurrence or survival. Stage-specific analyses in both cohorts revealed no association between adjuvant mitotane and improved RFS or OS.ConclusionsWhen accounting for stage and adverse tumor and treatment-related factors, adjuvant mitotane after resection of adrenocortical carcinoma is not associated with improved RFS or OS. Current guidelines should be revisited and prospective trials are needed.

ImportanceAdrenocortical carcinoma (ACC) is a rare but aggressive endocrine tumor, and the prognostic factors associated with long-term outcomes after surgical resection remain poorly defined.ObjectivesTo define clinicopathological variables associated with recurrence-free survival (RFS) and overall survival (OS) after curative surgical resection of ACC and to propose nomograms for individual risk prediction.Design, setting, and participantsNomograms to predict RFS and OS after surgical resection of ACC were proposed using a multi-institutional cohort of patients who underwent curative-intent surgery for ACC at 13 major institutions in the United States between March 17, 1994, and December 22, 2014. The dates of our study analysis were April 15, 2015, to May 12, 2015.Main outcomes and measuresThe discriminative ability and calibration of the nomograms to predict RFS and OS were tested using C statistics, calibration plots, and Kaplan-Meier curves.ResultsIn total, 148 patients who underwent surgery for ACC were included in the study. The median patient age was 53 years, and 65.5% (97 of 148) of the patients were female. One-third of the patients (35.1% [52 of 148]) had a functional tumor, and the median tumor size was 11.2 cm. Most patients (77.7% [115 of 148]) underwent R0 resection, and 8.8% (13 of 148) of the patients had N1 disease. Using backward stepwise selection of clinically important variables with the Akaike information criterion, the following variables were incorporated in the prediction of RFS: tumor size of at least 12 cm (hazard ratio [HR], 3.00; 95% CI, 1.63-5.70; P

BackgroundThe association of postoperative complications with long-term oncologic outcomes remains unclear. We sought to determine the incidence of complications among patients who underwent surgery for adrenocortical carcinoma (ACC) and define the relationship of morbidity with long-term survival.MethodsPatients who underwent surgery for ACC between 1993 and 2014 were identified from 13 academic institutions participating in the US ACC group study. The incidence and type of the postoperative complications, the factors associated with them as well their association with long-term survival were analyzed.ResultsA total of 265 patients with median age of 52 years (IQR 44-63) were identified; at surgery, the majority of patients underwent an open abdominal procedure (n = 169, 66.8%). A postoperative complication occurred in 99 patients for a morbidity of 37.4%; five patients (1.9%) died in hospital. Factors associated with morbidity included a thoraco-abdominal operative approach (reference: open abdominal; OR 2.85, 95% CI 1.00-8.18), and a hormonally functional tumor (OR 3.56, 95% CI 1.65-7.69) (all P < 0.05). Presence of any complication was associated with a worse long-term outcome (median survival: no complication, 58.9 months vs. any complication, 25.1 months; P = 0.009). In multivariate analysis, after adjusting for patient- and disease-related factors postoperative infectious complications independently predicted shorter overall survival (hazard ratio (HR) 5.56, 95% CI 2.24-13.80; P < 0.001).ConclusionPostoperative complications were independently associated with decreased long-term survival after resection for ACC. The prevention of complications may be important from an oncologic perspective.

BackgroundAdrenocortical carcinoma (ACC) is a rare malignancy. The aim of this study was to determine the incidence and patterns of recurrence after curative-intent surgery for ACC.MethodsPatients who underwent curative-intent resection for ACC between 1993 and 2014 were identified from 13 academic institutions participating in the United States ACC study group. Patients with metastasis or an R2 margin were excluded. Patterns and rates of recurrence were determined and classified as locoregional and distant recurrence.ResultsA total of 180 patients with a median age of 52 years (interquartile range 43-61) were identified. Most patients underwent open surgery (n = 111, 64.5 %) and had an R0 resection margin (n = 117, 75.0 %). At last follow-up, 116 patients (64.4 %) had experienced recurrence (locoregional only, n = 41, 36.3 %; distant only, n = 51, 45.1 %; locoregional and distant, n = 21, 18.6 %). Median time to recurrence was 18.8 months. Several factors were associated with locoregional recurrence, including left-sided ACC location (odds ratio [OR] 2.71, 95 % confidence interval [CI] 1.06-6.89) and T3/T4 disease (reference T1/T2, OR 3.04, 95 % CI 1.19-7.80) (both p < 0.05). Distant recurrence was associated with larger tumor size (OR 1.11, 95 % CI 1.01-1.24) and T3/T4 disease (reference T1/T2, OR 5.23, 95 % CI 1.70-16.10) (both p < 0.05). Patients with combined locoregional and distant recurrence had worse survival (3- and 5-year survival: 39.5, 19.7 %) versus patients with distant-only (3- and 5-year survival 55.1, 43.3 %) or locoregional-only recurrence (3- and 5-year survival 81.4, 64.1 %) (p = 0.01).ConclusionsNearly two-thirds of patients experienced disease recurrence after resection of ACC. Although a subset of patients experienced recurrence with locoregional disease only, many patients experienced recurrence with distant disease as a component of recurrence and had a poor prognosis.

BackgroundThe influence of surgical margin status on long-term outcomes of patients undergoing adrenal resection for ACC remains not well defined. We studied the impact of surgical tumor margin status on recurrence-free survival (RFS) and overall survival (OS) of patients undergoing resection for ACC.MethodsA total of 165 patients who underwent adrenal resection for ACC and met inclusion criteria were identified form a multi-institutional database. Clinicopathological data, pathologic margin status, and long-term outcomes were assessed. Patients were stratified into two groups based on margin status: R0 (margin >1 mm) versus R1.ResultsR0 resection was achieved in 126 patients (76.4 %), whereas 39 patients (23.6 %) had an R1 resection. Median and 5-year OS for patients undergoing R0 resection were 96.3 months and 64.8 % versus 25.1 months and 33.8 % for patients undergoing an R1 resection (both p < 0.001). On multivariable analysis, surgical margin status was an independent predictor of worse OS (hazard ratio [HR] 2.22, 95 % confidence interval [CI] 1.03-4.77; p = 0.04). The incidence of recurrence also differed between the two groups; 5-year RFS was 30.3 % among patients with an R0 resection versus 13.8 % among patients who had an R1 resection (p = 0.03). Lymph node metastasis (N1) was an independent predictor of RFS (HR 2.70, 95 % CI 1.04-6.99; p = 0.04).ConclusionsA positive margin after ACC resection was associated with worse long-term survival. Patient selection and an emphasis on surgical technique to achieve R0 margins are pivotal to optimizing the best chance for long-term outcome among patients with ACC.

BackgroundAdrenal venous sampling is an important lateralization study for primary aldosteronism, but inability to cannulate the right adrenal vein is not uncommon and interpreted as a failed study. We challenged this notion by examining whether data from incomplete left-sided adrenal venous sampling could accurately predict lateralization.MethodsSixty-two adrenal venous sampling studies from 2007 to 2014 at 2 tertiary-care institutions were reviewed. For this analysis, data from the right adrenal vein were excluded. The study variable was the aldosterone:cortisol ratio of the left adrenal vein compared with the inferior vena cava (LAV/IVC). Scatterplot analysis identified high and low LAV/IVC cutoffs that predicted accurately unilateral disease in 1 institutional cohort and validated in the second cohort.ResultsThirty-six studies of adrenal venous sampling were evaluated at the first institution and divided into 3 diagnostic categories: unilateral-left (n = 14), unilateral-right (n = 12), and bilateral (n = 10). Cutoff values of the ratios of LAV/IVC of ≥ 5.5 and ≤ 0.5 accurately predicted left- and right-sided disease, respectively, and were validated in 26 studies from the second institution (100% PPV). The "5.5-0.5 criteria" salvaged accuracy for predicting lateralization in 50% of cases.ConclusionEven in the setting of failed cannulation of the right adrenal vein, the actual data from the remaining adrenal venous sampling can predict lateralization accurately in many patients. A "failed" adrenal venous sampling study may be of greater predictive utility than believed traditionally.

ImportanceAdrenal incidentalomas are found in 1% to 5% of abdominal cross-sectional imaging studies. Although the workup and management of unilateral lesions are well established, limited information exists for bilateral incidentalomas.ObjectiveTo compare the natural history of patients having bilateral incidentalomas with those having unilateral incidentalomas.Design, setting, and participantsRetrospective analysis of a prospective database of consecutive patients referred to an academic multidisciplinary adrenal conference. The setting was a tertiary care university hospital among a cohort of 500 patients with adrenal lesions between July 1, 2009, and July 1, 2014.Main outcomes and measuresPrevalence, age, imaging characteristics, biochemical workup, any intervention, and final diagnosis.ResultsTwenty-three patients with bilateral incidentalomas and 112 patients with unilateral incidentalomas were identified. The mean age at diagnosis of bilateral lesions was 58.7 years. The mean lesion size was 2.4 cm on the right side and 2.8 cm on the left side. Bilateral incidentalomas were associated with a significantly higher prevalence of subclinical Cushing syndrome (21.7% [5 of 23] vs 6.2% [7 of 112]) (P = .009) and a significantly lower prevalence of pheochromocytoma (4.3% [1 of 23] vs 19.6% [22 of 112]) (P = .003) compared with unilateral lesions, while rates of hyperaldosteronism were similar in both groups (4.3% [1 of 23] vs 5.4% [6 of 112]) (P > .99). Only one patient with bilateral incidentalomas underwent unilateral resection. The mean follow-up was 4 years (range, 1.2-13.0 years). There were no occult adrenocortical carcinomas.Conclusions and relevanceBilateral incidentalomas are more likely to be associated with subclinical Cushing syndrome and less likely to be pheochromocytomas. Although patients with bilateral incidentalomas undergo a workup similar to that in patients with unilateral lesions, differences in their natural history warrant a greater index of suspicion for subclinical Cushing syndrome.

BackgroundThe presence and location of regional lymph node metastasis affect the prognosis of patients with thyroid cancer. Lymph node classification of the current TNM system may be inadequate because it insufficiently characterizes the nature and severity of lymph node metastasis that may influence prognosis.MethodsWe retrospectively studied 240 patients with papillary thyroid cancer and node metastases who had undergone total thyroidectomy, lymph node dissection, and postoperative (131) I treatment at the University Cancer Center between 1994 and 2004. We reviewed the status of regional lymph node metastasis, including the location, number, largest size, and extranodal tumor extension and analyzed their effect on the prognosis of the patients.ResultsThere were 172 women and 68 men, with a median age of 38 years and median tumor size of 1.9 cm. Thirty-five percent had only central compartment (N1a) nodal metastasis and 65% had involvement of both central and lateral compartments (N1b). There were a median of 4 nodes containing metastasis with a median largest diameter of 1.2 cm. Sixty patients (25%) had extranodal extension of cancer. Multivariate analysis showed that patient age (p = .0017; hazard ratio [HR], 2.156), >3 lymph node metastasis (p = .0316; HR, 1.806), and extranodal extension (p

BackgroundThe systemic inflammatory response may be associated with tumor progression. We sought to analyze the impact of neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) on recurrence-free survival (RFS) and disease-specific survival (DSS) among patients who underwent surgery for adrenocortical carcinoma (ACC).MethodsPatients undergoing surgery for ACC were identified from a multi-center database. Cut-off values of 5 and 190 were defined as elevated NLR and PLR, respectively, and long-term outcome was assessed.ResultsAmong 84 patients with ACC, 29 (34.%) had NLR > 5 while 32 (40.5%) had PLR > 190. NLR and PLR were associated with larger tumors (NLR > 5: ≤ 5 cm, 0% vs. >5 cm, 39.7%; PLR > 190: ≤ 5cm, 0% vs. >5 cm, 45.7%), as well as need to resect of other organs (NLR > 5: other organ resected 48.8% vs. not resected 20.9%; PLR > 190: other organ resected 25.0% vs. not resected 56.4%)(all P  5, 10.5%) and PLR (PLR ≤ 190: 19.4% vs. PLR > 190: 5.2%) (both P

BackgroundPreoperative tumor aggressiveness biomarkers may help surgeons decide the extent of an operation. However, whether serum angiogenetic factors can be used to predict the prognosis of patients with differentiated thyroid cancer is still unclear.MethodsSeventy-six DTC patients were prospectively recruited. Preoperative serum samples were collected and measured for Tie-2, Ang-1, Ang-2, VEGF-A, and VEGF-D levels. The potential correlations between their serum levels and clinicopathologic features as well as their prognoses were analyzed.ResultsOlder age (>45 years old) and higher VEGF-A serum levels were independent predictors of extrathyroidal extension. The VEGF-D serum level was an independent factor for lymph node metastases and VEGF-A was an independent factor for distant metastases. None of these serum angiogenetic factors were significantly different between patients who were disease free and those with recurrences. The presence of lymph node metastases was the only independent factor for recurrence over the 2-year follow-up.ConclusionPreoperative serum VEGF-A and VEGF-D levels were significantly elevated in DTC patients with distant and lymph node metastases. These findings, when combined with other clinicopathological factors, may help in surgical decisions.

The rate of unexpected thyroid cancers found at the time of thyroidectomy is thought to be similar in patients with cervical and substernal multinodular goiters (MNGs).The objective of this study was to compare the prevalence of undiagnosed cancer found in patients undergoing a thyroidectomy for a cervical or substernal MNG. We conducted a review of patients with a preoperative diagnosis of an MNG (both cervical and substernal) at a tertiary referral center between 2005 and 2012.We identified 538 patients who underwent thyroidectomy for an MNG (144 with substernal MNGs and 394 with cervical MNGs). Patients with substernal MNGs were older (59.6 vs. 52.3; p < 0.001), more likely to be men (34 vs. 11.1 %; p < 0.001), and less likely to have a history of radiation exposure to the neck (2.1 vs. 12.4 %; p < 0.001). Thyroid cancer (>1 cm) was found in 13.7 % of substernal MNG specimens and in 6.3 % of cervical MNG specimens (p = 0.003). On multivariate analysis, substernal location [odds ratio (OR) = 2.360; confidence interval (CI), 1.201-4.638] was the only variable independently associated with an unexpected thyroid cancer on surgical pathology.The rate of postoperatively discovered thyroid cancer is significant in patients with substernal MNGs and is increased when compared to patients with cervical MNGs. Surgeons should counsel their patients regarding the possibility of this unexpected result.

ImportanceUltrasound-guided fine needle aspiration (FNA) is an excellent tool for evaluating patients with solitary thyroid nodules, with a false-negative malignancy rate of 1 cm), and one patient with a papillary and follicular cancer]. On univariate analysis, male gender had a near-significant association with non-micropapillary thyroid cancer (p = 0.06). On multivariate analysis, male gender (OR = 10.2, 95% CI 1.35-76.8) and FNA cytology not reviewed at our institution (OR = 6.0, 95% CI 1.2-30) were independently associated with non-micropapillary thyroid cancer.Conclusions and relevanceThe incidence of thyroid cancer in patients with MNG and benign FNA is significant. Men and patients in whom the FNA cytology is not reviewed by an experienced cytopathologist may be at an increased risk for an undetected thyroid cancer.

BackgroundFine-needle aspiration cytology (FNAC) is very accurate in detecting papillary thyroid carcinomas (PTCs). According to the Bethesda system for reporting thyroid cytopathology, the risk for malignancy is 97-99% when FNAC is used to diagnose PTC; the malignancy risk is 60-75% when FNAC results in suspected PTCs. The presence of hyalinizing trabecular tumor (HTT) of the thyroid can cause misdiagnosis because its cytological features mimic PTCs. However, the use of frozen section analysis can assist in the recognition of unique architecture features of HTT, and thus may help prevent the undertaking of an unnecessarily aggressive operation.MethodsWe retrospectively reviewed all patients diagnosed with HTT by permanent histopathology from February 2009 to October 2013. After acquired agreement of the patients, we analyzed all data and reviewed another nine cases of HTT reported in the English-language medical literature to examine the efficacy of frozen section.ResultsThere were six patients included in our research (5 women and 1 man), with an average age of 48.8 years. Using frozen section, four patients were diagnosed with HTT and two patients were misinterpreted as PTC. Consequently, four patients had lobectomy and two patients had total thyroidectomy, with no surgical complications. Of the nine cases of HTT reviewed from the English literature, the use of frozen section showed three HTT cases, three PTC cases, two medullary thyroid carcinoma cases, and one deferral case. Overall, the use of frozen section as a diagnostic method prevented additional surgical resection in eight patients (53%).ConclusionFrozen section can sometimes but not always be used to diagnose HTT. When HTT is diagnosed by its trabecular pattern through the use of frozen section, it may prevent total thyroidectomy.

IntroductionProphylactic thyroidectomy can be curative for patients with hereditary medullary thyroid cancer (MTC) caused by RET proto-oncogene mutations. Calcitonin is a sensitive tumor marker used to follow patients. We suggest that thyroglobulin (Tg) levels should also be monitored postoperatively in these patients.MethodsWe reviewed patients with RET mutations who underwent prophylactic thyroidectomy between 1981 and 2011 at an academic endocrine surgery center. Patients were excluded if they had no postoperative Tg levels recorded.ResultsOf the 22 patients who underwent prophylactic thyroidectomy, 14 were included in the final analysis. The average age at thyroidectomy was 9.8 years (range, 4-29). Tg levels were detectable 1.5 months to 31 years postoperatively in 11 patients (79%), all of whom were

BackgroundAdrenalectomy is a complex procedure performed in many settings, with and without residents and fellows. Patients often ask, "Will trainees be participating in my operation?" and seek reassurance that their care will not be adversely affected. The purpose of this study was to determine the association between trainee participation and adrenalectomy perioperative outcomes.Study designWe performed a cohort study of patients who underwent adrenalectomy from the 2005 to 2011 American College of Surgeons NSQIP database. Trainee participation was classified as none, resident, or fellow, based on postgraduate year of the assisting surgeon. Associations between trainee participation and outcomes were determined via multivariate linear and logistic regression.ResultsOf 3,694 adrenalectomies, 732 (19.8%) were performed by an attending surgeon with no trainee, 2,315 (62.7%) involved a resident, and 647 (17.5%) involved a fellow. The participation of fellows was associated with fewer serious complications (7.9% with no trainee, 6.0% with residents, and 2.8% with fellows; p < 0.001). In a multivariate model, the odds of serious 30-day morbidity were lower when attending surgeons operated with residents (odds ratio = 0.63; 95% CI, 0.45-0.89). Fellow participation was associated with significantly lower odds of overall (odds ratio = 0.51; 95% CI, 0.32-0.82) and serious (odds ratio = 0.31; 95% CI, 0.17-0.57) morbidity. There was no significant association between trainee participation and 30-day mortality.ConclusionsIn this analysis of multi-institutional data, the participation of residents and fellows was associated with decreased odds of perioperative adrenalectomy complications. Attending surgeons performing adrenalectomies with trainee assistance should reassure patients of the equivalent or superior care they are receiving.

BackgroundThe goal of this study was to review a single institution's experience using intraoperative ultrasound-guided (ioUSG) methylene blue dye injection for the localization and removal of enlarged parathyroid glands in patients with primary hyperparathyroidism and a history of previous neck surgery.MethodsWe performed a retrospective review of nine consecutive patients who underwent reoperative parathyroidectomy using ioUSG methylene blue dye injection.ResultsAll patients had successful resolution of their hyperparathyroidism, with at least a 50 % decrease in intraoperative parathyroid hormone level after resection. One patient had transient recurrent laryngeal nerve paresis. There were no permanent recurrent laryngeal nerve injuries or cases of permanent hypoparathyroidism.ConclusionsBlue dye injection is a safe and effective method of localizing diseased parathyroid glands in the reoperative neck.

We evaluated an African American woman referred in 1986 at age 33 years because of renal potassium and calcium wasting and chronic hip pain. She presented normotensive, hypokalemic, hypocalcemic, normophosphatemic, and hypercalciuric. Marked hyperparathyroidism was evident. Urinary cyclic adenosine monophosphate (cAMP) excretion did not increase in response to parathyroid hormone (PTH) infusion, indicating renal resistance to PTH. X-rays and bone biopsy revealed severe osteitis fibrosa cystica, confirming skeletal responsiveness to PTH. Renal potassium wasting, suppressed plasma renin activity, and elevated plasma and urinary aldosterone levels accompanied her hypokalemia, suggesting primary hyperaldosteronism. Hypokalemia resolved with spironolactone and, when combined with dietary sodium restriction, urinary calcium excretion fell and hypocalcemia improved, in accord with the known positive association between sodium intake and calcium excretion. Calcitriol and oral calcium supplements did not suppress the chronic hyperparathyroidism nor did they reduce aldosterone levels. Over time, hyperparathyroid bone disease progressed with pathologic fractures and persistent pain. In 2004, PTH levels increased further in association with worsening chronic kidney disease. Eventually hypercalcemia and hypertension developed. Localizing studies in 2005 suggested a left inferior parathyroid tumor. After having consistently declined, the patient finally agreed to neck exploration in January 2009. Four hyperplastic parathyroid glands were removed, followed immediately by severe hypocalcemia, attributed to "hungry bone syndrome" and hypoparathyroidism, which required prolonged hospitalization, calcium infusions, and oral calcitriol. Although her bone pain resolved, hyperaldosteronism persisted.