Clinical Significance of Pheochromocytoma Size on the Timing and Extent of Surgery.

INTRODUCTION: Elevated metanephrine and catecholamine levels 3-fold upper limit of normal (ULN) are diagnostic for pheochromocytoma. We sought to determine whether size correlates with biochemical activity or symptoms which could guide timing of surgery. METHODS: Data from consecutive patients undergoing adrenalectomy for pheochromocytoma at our institution over a 10-year period were retrospectively collected. These included maximal lesion diameter on preoperative imaging, plasma/urine metanephrine and/or catecholamine levels, demographic variables and presence of typical paroxysmal symptoms. Receiver operating characteristic curves were used to assess predictive accuracy. RESULTS: Sixty-three patients were included in the analysis (41 females and 22 males). Median age was 56 (43, 69) years. Due to various referring practices, 31 patients had documented 24-h urine metanephrine, 26 had 24-h urine catecholamine, and 52 had fractionated plasma metanephrine levels available for review. Values were converted to fold change compared to ULN and the maximum of all measured values was used for logistic regression. Median tumor size was 3.40 (2.25, 4.55) cm in greatest dimension. Tumor size at which pheochromocytoma produced > 3-fold ULN was ≥2.3 cm (AUC of 0.84). Biochemical activity increased with doubling tumor size (odds ratio = 8, P = 0.0004) or ≥ 1 cm increase in tumor size (odds ratio = 3.03, P = 0.001). 40 patients had paroxysmal symptoms, but there was no significant correlation between tumor size/biochemical activity and symptoms. CONCLUSIONS: In our study, tumor size directly correlated with the degree of biochemical activity and pheochromocytomas ≥2.3 cm produced levels 3 times ULN. These findings may allow clinicians to adjust timing of operative intervention.

Morbidity and Outcomes of Primary Tumor Management in Patients with Widely Metastatic Well-Differentiated Small Bowel Neuroendocrine Tumors.

BACKGROUND: The benefit of primary tumor resection in distant metastatic small bowel neuroendocrine tumors (SBNETs) is controversial, with treatment-based morbidity not well-defined. We aimed to determine the impact of primary tumor resection on development of disease-specific complications in patients with metastatic well-differentiated SBNETs. PATIENTS AND METHODS: A retrospective analysis was performed of patients diagnosed with metastatic well-differentiated jejunal/ileal SBNETs at a single tertiary care cancer center from 1980 to 2016. Outcomes were compared on the basis of treatment selected at diagnosis between patients who underwent initial medical treatment or primary tumor resection. RESULTS: Among 180 patients, 71 underwent medical management and 109 primary tumor resection. Median follow-up was 116 months. Median event-free survival did not differ between treatment approaches (log-rank p = 0.2). In patients medically managed first, 16/71 (23%) required surgery due to obstruction, perforation, or bleeding. These same complications led to resection at presentation in 31/109 (28%) surgically treated patients. Development of an obstruction from the primary tumor was not associated with disease progression/recurrence (HR 1.14, 95% CI 0.75-1.75) with all patients recovering postoperatively. Ongoing tumor progression requiring secondary laparotomy was associated with worse mortality (HR 7.51, 95% CI 3.3-16.9; p < 0.001) and occurred in 20/109 (18%) primary tumor resection and 7/16 (44%) initially medically treated patients. CONCLUSIONS: Rates of event-free survival among patients with metastatic SBNETs do not differ on the basis of primary tumor management. The development of an obstruction from the primary tumor was not associated with worse outcomes with all patients salvaged. Regardless of initial treatment selected, patients with metastatic SBNET should be closely followed for early signs of primary tumor complications.

Thyroidectomy Outcomes in Obese Patients.

INTRODUCTION: Obese patients often have higher complication rates after elective general surgeries; however, few studies have examined the outcomes after thyroidectomy. This study examines whether increased body mass index (BMI) is associated with poor postoperative outcomes after thyroid surgery. METHODS: A retrospective review of patients who underwent thyroidectomy from 2015 to 2018 was performed. Demographics, comorbidities, pathology, and extent of resection (total versus hemithyroidectomy) were examined. Patients were classified into BMI groups according to the WHO definitions, and the incidence of surgical outcomes was determined in each group. Surgical outcomes of interest included readmission rates (RRs), length of stay, average operating room time, return to the operating room, hypocalcemia, postop infections, hematomas, and recurrent laryngeal nerve injury. Between-subjects statistics including independent samples t-test, ANOVA, and chi-square analyses were performed. RESULTS: There were n = 465 patients included with a mean BMI 32.35 (standard deviation = 8.55) and median BMI 30.78 (Q1 = 26.26, Q3 = 36.73). There were no differences between BMI groups in age, gender, smoking, heart disease. There was a positive association between increased BMI and postoperative infection (P < 0.001), pneumonia (P = 0.018), and surgical site infection (P = 0.04), which were highest for BMI > 40. Increased BMI was associated with a higher 30-d RR (P = 0.008), particularly for BMI >40 versus BMI <40 (6.2% versus 1.05%; P = 0.003). There were no significant differences between surgical outcomes for patients with increased BMI who underwent total thyroidectomy or hemithyroidectomy. CONCLUSIONS: Excellent postoperative outcomes were observed in all BMI categories. Higher postoperative infection and 30-d RRs were observed in the morbidly obese. Contrary to previous studies, operating room times were similar regardless of BMI.

Prognostic factors and survival analysis of Hurthle cell carcinoma: A population-based study.

BACKGROUND: Hurthle cell carcinoma is a rare type of differentiated thyroid cancer and historically associated with a worse prognosis. The aim of this study was to define the demographic and socioeconomic factors, tumor characteristics, and surgical treatment status associated with Hurthle cell carcinoma survival using the most recent population-level data. METHODS: The Surveillance, Epidemiology, and End Results database was queried for adult patients (>18 years of age) diagnosed with Hurthle cell carcinoma from 2000 to 2018. The demographic factors, socioeconomic factors, tumor characteristics, and extent of surgery data were collected as potential predictors. The outcomes of interest were 10-year overall and disease-specific survival, which were estimated using the Kaplan-Maier method. The associations between the potential predictors and survival were evaluated using the Cox proportional hazard model. RESULTS: In total, 4,643 patients with Hurthle cell carcinoma were identified using the Surveillance, Epidemiology, and End Results database. The cohort was predominately White, had a mean age of 57.7 (±15.6), 69% female sex, and median follow-up was 90 months. The 10-year overall survival and Hurthle cell carcinoma-specific survival were 78.1% (95% confidence interval: 76.7%-79.5%) and 91.8% (95% confidence interval: 90.9%-92.9%), respectively. Younger age <55 years, female sex, White race, Hispanic ethnicity, higher household income, and lower tumor grade and stage were significantly associated with increased survival (P < .01). In the multivariate Cox proportional hazard model, all variables except race and ethnicity remained significantly associated with overall survival. Although patients who underwent thyroid surgery had improved survival compared to no surgery, the extent of surgery did not have any effect on their overall or disease-specific survival. CONCLUSION: This study highlighted the aggressive nature of Hurthle cell carcinoma and the effect of socioeconomic factors, such as household income, which may play a role in Hurthle cell carcinoma survivorship. Research is needed to understand the interplay of these factors and their role in predicting patient outcomes.

Effect of Intraoperative Neuromonitoring on the Risks of Recurrent Laryngeal Nerve Injury During Thyroidectomy: A Doubly Robust Approach.

OBJECTIVE: To evaluate the relationship between the use intraoperative neuromonitoring (IONM) during thyroidectomy and the risk of recurrent laryngeal nerve (RLN) injury. BACKGROUND: The role of IONM in reducing RLN injury during thyroidectomy remains controversial. Several studies on this topic apply conventional multivariable regression to adjust for confounding. However, estimates from this method may be biased due to model misspecification, especially with a rare outcome such as RLN injury. METHODS: We used a pooled dataset created by linking the 2016-2019 National Surgical Quality Improvement Project General Participant User File with the corresponding Targeted-Thyroidectomy file. The primary outcome was RLN injury rates, and the secondary outcomes were operating time and postoperative length of stay. A doubly robust (DR) estimator, in the form of an inverse-probability-weighted regression adjustment model, was used to estimate the effect of the use of IONM on the risk of RLN injury. Sensitivity analyses was performed. RESULTS: Twenty-four thousand three hundred seventy patients were evaluated, out of which 15,836 (70%) patients had IONM during thyroidectomy, and RLN injury occurred in 1498 (6.2%) cases. Rates of RLN injury increase with increasing age and BMI and are higher in patients with a cancer diagnosis, previous neck operation, total thyroidectomy, and node dissection. Doubly robust model suggests that the use of IONM was associated with a significant reduction in overall rate of RLN injury [risk ratio 0.77, confidence interval (CI), 0.68-0.87, P <0.001], and postoperative length of stay [-2.5 hours (CI, -4.18 to -0.81 h), P =0.004]. However, IONM use was associated with an increase in operating time [15.41 minutes (CI, 13.29-17.54 minutes), P <0.0001]. Sensitivity analyses revealed that our estimates are largely robust to confounding. CONCLUSION: In a balanced cohort of patients undergoing thyroidectomy from multiple sites and surgeons participating in National Surgical Quality Improvement Project, the use of IONM during thyroidectomy was associated with reduction in RLN injury.

A machine-learning algorithm for distinguishing malignant from benign indeterminate thyroid nodules using ultrasound radiomic features.

Background: Ultrasound (US)-guided fine needle aspiration (FNA) cytology is the gold standard for the evaluation of thyroid nodules. However, up to 30% of FNA results are indeterminate, requiring further testing. In this study, we present a machine-learning analysis of indeterminate thyroid nodules on ultrasound with the aim to improve cancer diagnosis. Methods: Ultrasound images were collected from two institutions and labeled according to their FNA (F) and surgical pathology (S) diagnoses [malignant (M), benign (B), and indeterminate (I)]. Subgroup breakdown (FS) included: 90 BB, 83 IB, 70 MM, and 59 IM thyroid nodules. Margins of thyroid nodules were manually annotated, and computerized radiomic texture analysis was conducted within tumor contours. Initial investigation was conducted using five-fold cross-validation paradigm with a two-class Bayesian artificial neural networks classifier, including stepwise feature selection. Testing was conducted on an independent set and compared with a commercial molecular testing platform. Performance was evaluated using receiver operating characteristic analysis in the task of distinguishing between malignant and benign nodules. Results: About 1052 ultrasound images from 302 thyroid nodules were used for radiomic feature extraction and analysis. On the training/validation set comprising 263 nodules, five-fold cross-validation yielded area under curves (AUCs) of 0.75 [Standard Error (SE) = 0.04; P < 0.001 ] and 0.67 (SE = 0.05; P = 0.0012 ) for the classification tasks of MM versus BB, and IM versus IB, respectively. On an independent test set of 19 IM/IB cases, the algorithm for distinguishing indeterminate nodules yielded an AUC value of 0.88 (SE = 0.09; P < 0.001 ), which was higher than the AUC of a commercially available molecular testing platform (AUC = 0.81, SE = 0.11; P < 0.005 ). Conclusion: Machine learning of computer-extracted texture features on gray-scale ultrasound images showed promising results classifying indeterminate thyroid nodules according to their surgical pathology.

Total Thyroidectomy vs Thyroid Lobectomy for Localized Papillary Thyroid Cancer in Children: A Propensity-Matched Survival Analysis.

BACKGROUND: Current guidelines recommend total thyroidectomy (TT) and radioablation for most papillary thyroid cancer (PTC) in children. These guidelines have been criticized as aggressive, especially for early-stage PTC, as it likely does not influence patient survival and results in life-long thyroid hormone replacement. We sought to study whether the extent of thyroidectomy (TT vs thyroid lobectomy [TL]) influences overall and disease-specific survival in children with localized PTC. METHODS: The National Cancer Database and the Surveillance, Epidemiology, and End Results registries were queried. Patients 18 years or younger with low-risk PTC between 2004 and 2016 were included. Using a 1:1 propensity score matching, patients who underwent TT were matched for age, sex, race, year of diagnosis, and tumor size with a similar cohort of patients who underwent TL. Primary end points were overall survival and disease-specific survival. RESULTS: There were 3,500 patients identified as surgically treated for PTC, of which 1,325 patients met inclusion criteria for matching. Three hundred and twenty-six patients were matched. One hundred and sixty-three patients had TT; 140 were female and mean age was 16 years (interquartile range [IQR] 13 to 17 years). One hundred and sixty-three patients had TL; 140 were female and mean age was 16 years (IQR 14 to 17 years). Median follow-up was 5.0 years (IQR 2.8 to 8 years) and 8.3 years (IQR 3.6 to 14.4 years) in the National Cancer Database and Surveillance, Epidemiology, and End Results cohorts, respectively. There was no statistically significant difference in overall survival or disease-specific survival in patients with PTC < 4 cm, regardless of whether patients underwent TT or TL (p = 0.32 for National Cancer Database registry and p = 0.67 for Surveillance, Epidemiology, and End Results registry). CONCLUSIONS: This study suggests that the extent of thyroidectomy does not influence survival for pediatric patients with early-stage PTC and that TL might be adequate in this patient population.

Response rates in metastatic neuroendocrine tumors receiving peptide receptor radionuclide therapy and implications for future treatment strategies.

BACKGROUND: Peptide receptor radionuclide therapy is a targeted therapy used to treat unresectable somatostatin receptor-positive neuroendocrine tumors. The objective of this study was to evaluate response rates among neuroendocrine tumors of different primaries and identify factors relevant to future treatment strategies. METHODS: We retrospectively reviewed patients who received peptide receptor radionuclide therapy for neuroendocrine tumors from 2018 to 2019 at our institution. Patients were assessed with computed tomography/magnetic resonance imaging and 68Ga-DOTATATE-positron emission tomography before and after 2 or 4 cycles of peptide receptor radionuclide therapy. Tumor response was evaluated by RECIST 1.1. Statistics included multinomial logistic regression models and Fisher exact test. RESULTS: Twenty-seven patients underwent 92 cycles of peptide receptor radionuclide therapy: pancreas (n = 11), small bowel (n = 7), and other (n = 9) neuroendocrine tumors. Overall, 30% (8 of 27) had partial response, 59% (16 of 27) stable disease, and 11% (3 of 27) progressed. Pancreatic neuroendocrine tumors responded differently from small bowel neuroendocrine tumors regardless of cycle number (P = .01). The majority of pancreatic neuroendocrine tumors (6 of 11) had partial response to peptide receptor radionuclide therapy, while all small bowel neuroendocrine tumors had stable disease. Pancreatic neuroendocrine tumors stable after 2 cycles were more likely to respond to additional cycles versus other neuroendocrine tumors (probability: 60% vs 11%). CONCLUSION: Patients with unresectable advanced or metastatic pancreatic neuroendocrine tumors may benefit from a full course of peptide receptor radionuclide therapy, whereas other neuroendocrine tumors appear less likely to respond. Large prospective studies are needed to confirm these findings.

Thyroidectomy for euthyroid patients with Hashimoto thyroiditis and persisting symptoms: A cost-effectiveness analysis.

BACKGROUND: Despite thyroid hormone replacement, some euthyroid patients with Hashimoto thyroiditis will continue to experience persistent symptoms that reduce their quality of life. Recent studies indicate that total thyroidectomy is superior to medical therapy alone in improving these symptoms. However, there is a high complication rate after total thyroidectomy in patients with Hashimoto thyroiditis. This study evaluates the cost-effectiveness of total thyroidectomy for euthyroid patients who have Hashimoto thyroiditis with persistent symptoms. METHODS: We utilized a Markov model to compare total thyroidectomy and medical therapy alone over the lifetime of the cohort. Costs, probabilities, and utility parameters were derived from literature and Medicare cost data. A willingness-to-pay threshold of $100,000/quality-adjusted life years was used. We performed sensitivity analyses to ascertain model uncertainty. RESULTS: On average, medical therapy alone costs $12,845, produced 16.9 quality-adjusted life years, and was dominated. Total thyroidectomy costs $1,490 less and produced 1.4 more quality-adjusted life years. Probabilistic sensitivity analysis confirmed total thyroidectomy as the optimal strategy in 89% of cases. Medical therapy alone will become cost-effective if the cost of uncomplicated thyroidectomy increases by 25%, if the probability of permanent complication after total thyroidectomy increases 12-fold, or if there is no gain in quality of life after thyroidectomy. CONCLUSION: Total thyroidectomy is more cost-effective than medical therapy alone for the management of euthyroid patients who have Hashimoto thyroiditis with persistent symptoms.

PRE-OPERATIVE LOCALIZATION OF PARATHYROID ADENOMA: PERFORMANCE OF 4D MRI PARATHYROID PROTOCOL.

Objective: Accurate pre-operative image localization is critical in the selection of minimally invasive parathyroidectomy as a surgical treatment approach in patients with primary hyperparathyroidism (PHPT). Sestamibi scan, ultrasound, computed tomography, and conventional magnetic resonance imaging (MRI) has varying accuracy in localizing parathyroid adenoma (PTA). Our group has previously shown that four-dimensional (4D) MRI is more accurate than conventional imaging in identifying single adenomas. In this study, we set out to determine if it is possible to accurately localize the quadrant of the adenoma using 4D MRI. Methods: We analyzed and matched the quadrants of PTA identified by pre-operative 4D-MRI with the operative findings during parathyroidectomy for PHPT at our institution during the study period. All resections were confirmed to be successful with an adequate decrease in intraoperative parathyroid hormone as defined by the Miami criterion. Results: A total of 26 patients with PHPT underwent pre-operative localization with the 4D MRI parathyroid protocol. Fourteen patients had true single-gland adenoma (SGA) and 12 patients had multi-gland disease (MGD). 4D MRI accurately identified all the SGA. Using this method, we were also able to localize the adenoma in the correct quadrant in 14 of the 18 patients with SGA. All 3 double adenomas were accurately identified using 4D MRI; however, MGD was only accurately identified 67% of the time. The 4D MRI had an overall 85% accuracy in distinguishing SGA from MGD. Conclusion: 4D MRI accurately identified single and double adenomas in their respective quadrants. However, accuracy was lower with MGD. Abbreviations: BNE = bilateral neck exploration; CT = computed tomography; IOPTH = intra-operative parathyroid hormone; MGD = multi-gland disease; MIBI = sestamibi; MIP = minimally invasive parathyroidectomy; MRI = magnetic resonance imaging; PHPT = primary hyperparathyroidism; PTA = parathyroid adenoma; PTH = parathyroid hormone; SGA = single-gland adenoma; SPECT = single photon emission computed tomography; 4D = four-dimensional.