HCC EV ECG score: An extracellular vesicle-based protein assay for detection of early-stage hepatocellular carcinoma.

BACKGROUND AND AIMS: The sensitivity of current surveillance methods for detecting early-stage hepatocellular carcinoma (HCC) is suboptimal. Extracellular vesicles (EVs) are promising circulating biomarkers for early cancer detection. In this study, we aim to develop an HCC EV-based surface protein assay for early detection of HCC. APPROACH AND RESULTS: Tissue microarray was used to evaluate four potential HCC-associated protein markers. An HCC EV surface protein assay, composed of covalent chemistry-mediated HCC EV purification and real-time immuno-polymerase chain reaction readouts, was developed and optimized for quantifying subpopulations of EVs. An HCC EV ECG score, calculated from the readouts of three HCC EV subpopulations ( E pCAM + CD63 + , C D147 + CD63 + , and G PC3 + CD63 + HCC EVs), was established for detecting early-stage HCC. A phase 2 biomarker study was conducted to evaluate the performance of ECG score in a training cohort ( n  = 106) and an independent validation cohort ( n  = 72).Overall, 99.7% of tissue microarray stained positive for at least one of the four HCC-associated protein markers (EpCAM, CD147, GPC3, and ASGPR1) that were subsequently validated in HCC EVs. In the training cohort, HCC EV ECG score demonstrated an area under the receiver operating curve (AUROC) of 0.95 (95% confidence interval [CI], 0.90-0.99) for distinguishing early-stage HCC from cirrhosis with a sensitivity of 91% and a specificity of 90%. The AUROCs of the HCC EV ECG score remained excellent in the validation cohort (0.93; 95% CI, 0.87-0.99) and in the subgroups by etiology (viral: 0.95; 95% CI, 0.90-1.00; nonviral: 0.94; 95% CI, 0.88-0.99). CONCLUSION: HCC EV ECG score demonstrated great potential for detecting early-stage HCC. It could augment current surveillance methods and improve patients' outcomes.

The Effect of Hyperosmolar Water-Soluble Contrast for the Management of Adhesive Small Bowel Obstruction: A Systematic Review and Meta-Analysis.

OBJECTIVE: To better understand the efficacy of water-soluble contrast (WSC) in the treatment of adhesive small bowel obstruction (SBO). BACKGROUND: Guidelines recommend using WSC to treat adhesive SBO nonoperatively by acting as a cathartic agent. The evidence supporting this practice is mixed. METHODS: A systematic review and meta-analysis of published articles describing the effect of WSC compared with control treatments was performed for the period of January 1, 1990 to November 1, 2021. Study quality was assessed using the Cochrane risk-of-bias and the Newcastle-Ottawa tools. The therapeutic effect of WSC was assessed by operative rates and hospital length of stay (HLOS) in nonsurgical patients. RESULTS: The initial search yielded 4879 articles, of which, 28 were selected for full text review. We identified 11 eligible randomized controlled trials (RCTs) which included 817 patients and 9 observational studies of 3944 patients. HLOS in nonsurgical patients decreased by 1.95 days (95% confidence interval: 0.56-3.3) in the RCTs and could not be assessed in the observational studies. WSC did not significantly affect operative rates in the RCTs (19.8% vs. 21.4%) but did reduce rates in the observational studies (11% vs. 16%, risk ratio: 0.56, 95% confidence interval: 0.39-0.82). CONCLUSION: WSC studies may reduce HLOS for patients who have SBO and do not require surgery. However, the current literature is heterogenous with considerable design limitations. High-quality RCTs are needed using standardized protocols to determine the full benefit of WSC for the management of SBO.

Perception of risk and treatment decisions in the management of differentiated thyroid cancer.

BACKGROUND AND OBJECTIVES: The recent de-escalation of care for differentiated thyroid cancer (DTC) has broadened the range of initial treatment options. We examined the association between physicians' perception of risk and their management of DTC. METHODS: Thyroid specialists were surveyed with four clinical vignettes: (1) indeterminate nodule (2) tall cell variant papillary thyroid cancer (PTC), (3) papillary thyroid microcarcinoma (mPTC), and (4) classic PTC. Participants judged the operative risks and likelihood of structural cancer recurrence associated with more versus less aggressive treatments. A logistic mixed effect model was used to predict treatment choice. RESULTS: Among 183 respondents (13.4% response rate), 44% were surgical and 56% medical thyroid specialists. Risk estimates and treatment recommendation varied markedly in each case. Respondents' estimated risk of 10-year cancer recurrence after lobectomy for a 2.0-cm PTC ranged from 1% to 53% (interquartile range [IQR]: 3%-12%), with 66% recommending lobectomy and 34% total thyroidectomy. Respondents' estimated 5-year risk of metastastic disease during active surveillance of an 0.8-cm mPTC ranged from 0% to 95% (IQR: 4%-15%), with 36% choosing active surveillance. Overall, differences in perceived risk reduction explained 10.3% of the observed variance in decision-making. CONCLUSIONS: Most of the variation in thyroid cancer treatment aggressiveness is unrelated to perceived risk of cancer recurrence.

Trends in Adjuvant External Beam Radiation Therapy for Nonanaplastic Thyroid Cancer in California, 2003-2017.

BACKGROUND: External beam radiation therapy (EBRT) is rarely used to treat patients with differentiated or medullary thyroid cancer. Although EBRT is generally administered to patients with high-risk or unresectable diseases, neither its indications for the use nor the associated outcomes are well-defined. We used a statewide cohort to assess the trends in EBRT use and postradiation outcomes in California. METHODS: A population-based study of patients within the California Cancer Registry who underwent EBRT after surgery for nonanaplastic thyroid cancer (2003-2017) was conducted. The primary outcome was the annual utilization rate of EBRT. The secondary outcomes included Kaplan-Meier analysis for cause-specific survival and identifying factors associated with improved survival after EBRT. RESULTS: Among the 57 607 patients with nonanaplastic thyroid cancer from 2003 to 2017, 344 (0.6%) patients received EBRT. EBRT was utilized in 0.4% of papillary, 1.1% of follicular, and 7.7% of medullary thyroid cancers in California. Overall, 99 (28.8%) patients treated with EBRT died of thyroid cancer. The 10-year cause-specific survival of all patients with thyroid cancer after EBRT was 61.5% (95% CI: 54.8%-69.1%) and that of patients without distant disease was 80.3% (95% CI: 73.5%-87.8%). The survival outcomes varied by tumor size, histology, disease stage, patient age at diagnosis, and the presence of extrathyroidal extension (P < .05). CONCLUSIONS: The use of adjuvant EBRT for nonanaplastic thyroid cancer remained stable and low in California from 2003 to 2017. The comparative efficacy of EBRT was not discernible in this study, but disease control appeared durable in select patients. Well-controlled observational studies and/or prospective studies are needed to better define which patients benefit from EBRT.

Cost Saving of Short Hospitalization Nonoperative Management for Acute Uncomplicated Appendicitis.

BACKGROUND: Nonoperative management (NOM) of uncomplicated appendicitis has gained recognition as an alternative to surgery. In the largest published randomized trial (Appendicitis Acuta), patients received a 3-d hospital stay for intravenous antibiotics; however, cost implications for health care systems remain unknown. We hypothesized short stay protocols would be cost saving compared with a long stay protocol. MATERIALS AND METHODS: We constructed a Markov model comparing the cost of three protocols for NOM of acute uncomplicated appendicitis: (1) long stay (3-d hospitalization), (2) short stay (1-d hospitalization), and (3) emergency department (ED) discharge. The long stay protocol was modeled on data from the APPAC trial. Model variables were abstracted from national database and literature review. One-way and two-way sensitivity analyses were performed to determine the impact of uncertainty on the model. RESULTS: The long stay treatment protocol had a total 5-y projected cost of $10,735 per patient. The short stay treatment protocol costs $8026 per patient, and the ED discharge protocol costs $6,825, which was $2709 and $3910 less than the long stay protocol, respectively. One-way sensitivity analysis demonstrated that the relative risk of treatment failure with the short stay protocol needed to exceed 6.3 (absolute risk increase of 31%) and with the ED discharge protocol needed to exceed 8.75 (absolute risk increase of 45%) in order for the long stay protocol to become cost saving. CONCLUSIONS: Short duration hospitalization protocols to treat appendicitis nonoperatively with antibiotics are cost saving under almost all model scenarios. Future consideration of patient preferences and health-related quality of life will need to be made to determine if short stay treatment protocols are cost-effective.

Prospective anatomical study to determine the site of insertion of recurrent laryngeal nerve into the larynx.

OBJECTIVES: Determine whether the insertion site of the recurrent laryngeal nerve (RLN) occurs at a predictable distance from the midline trachea, to help guide safe dissection during thyroid surgery. DESIGN: Prospective clinical trial. At the inferior edge of the cricoid cartilage, we measured the distance from mildline trachea to the RLN insertion site. SETTING: Single institution. PARTICIPANTS: 50 consecutive patients undergoing thyroid surgery. MAIN OUTCOME MEASURES: Distance from midline trachea to laryngeal insertion of RLN. RESULTS: The study population included 36 women and 14 men, with 72 total nerves measured. The average distance-to-midline + standard deviation (range) of the RLN was 20.7 + 2.3 (17-26) mm in women compared to 26.3 + 2.1 (22-32) mm in men. CONCLUSION: The insertion point of the RLN into the larynx at the level of inferior border of the cricoid cartilage can be reliably predicted, to facilitate early identification of the RLN during thyroid surgery.

Impact of intraoperative remifentanil on postoperative pain and opioid use in thyroid surgery.

BACKGROUND AND OBJECTIVES: Remifentanil infusion is used as an intraoperative anesthetic for thyroidectomy, but has been associated with acute opioid tolerance and hyperalgesia. A national shortage of remifentanil provided an opportunity to study postoperative pain in patients undergoing thyroidectomy. METHODS: Retrospective review of prospectively collected data from an outpatient surgery center. Primary analysis compared patients treated before and after remifentanil shortage. RESULTS: Median postoperative opioid consumption was 20 morphine milligram equivalents (MMEs) among those treated in the high-dose period and 15 MMEs in the low-dose period. Remifentanil/weight received was a significant predictor of requiring a postoperative narcotic (P = .006). Total non-remifentanil narcotics administered were equivalent but patients in the low dose period received higher amounts of intraoperative long-acting narcotics. CONCLUSIONS: Remifentanil infusion for thyroid surgery is associated with higher postoperative pain and postoperative narcotics requirement. While a hyperalgesia state is possible, shifting of longer-acting narcotics from intraoperative to postoperatively is also supported.

Cost Effectiveness of Routine Laryngoscopy in the Surgical Treatment of Differentiated Thyroid Cancer.

BACKGROUND: Some surgeons perform flexible fiberoptic laryngoscopy (FFL) in all patients prior to thyroid cancer operations. Given the low likelihood of recurrent laryngeal nerve (RLN) or aerodigestive invasion in clinically low-risk thyroid cancers, the value of routine FFL in this group is controversial. We hypothesized that routine preoperative FFL would not be cost effective in low-risk differentiated thyroid cancer (DTC). METHODS: A decision model was constructed comparing preoperative FFL versus surgery without FFL in a clinical stage T2 N0 DTC patient without voice symptoms. Total thyroidectomy and definitive hemithyroidectomy were both modeled as possible initial surgical approaches. Outcome probabilities and their corresponding utilities were estimated via literature review, and costs were estimated using Medicare reimbursement data. Sensitivity analysis was conducted to examine the uncertainty of cost, probability, and utility estimates in the model. RESULTS: When the initial surgical strategy was total thyroidectomy, routine preoperative FFL produced an incremental cost of $183 and an incremental effectiveness of 0.000126 quality-adjusted life-years (QALYs). The incremental cost-effectiveness ratio (ICER) for routine FFL prior to total thyroidectomy was $1.45 million/QALY, exceeding the $100,000/QALY threshold for cost effectiveness. Routine FFL became cost effective if the preoperative probability of asymptomatic vocal cord paralysis increased from 1.0% to 4.9%, or if the cost of preoperative FFL decreased from $128 to $27. Changing the extent of initial surgery to hemithyroidectomy produced a higher ICER for routine FFL of $1.7 million/QALY. CONCLUSION: Routine preoperative FFL is not cost effective in asymptomatic patients with sonographically low-risk DTC, regardless of the initial planned extent of surgery.

Antibiotics-First Versus Surgery for Appendicitis: A US Pilot Randomized Controlled Trial Allowing Outpatient Antibiotic Management.

STUDY OBJECTIVE: Randomized trials suggest that nonoperative treatment of uncomplicated appendicitis with antibiotics-first is safe. No trial has evaluated outpatient treatment and no US randomized trial has been conducted, to our knowledge. This pilot study assessed feasibility of a multicenter US study comparing antibiotics-first, including outpatient management, with appendectomy. METHODS: Patients aged 5 years or older with uncomplicated appendicitis at 1 US hospital were randomized to appendectomy or intravenous ertapenem greater than or equal to 48 hours and oral cefdinir and metronidazole. Stable antibiotics-first-treated participants older than 13 years could be discharged after greater than or equal to 6-hour emergency department (ED) observation with next-day follow-up. Outcomes included 1-month major complication rate (primary) and hospital duration, pain, disability, quality of life, and hospital charges, and antibiotics-first appendectomy rate. RESULTS: Of 48 eligible patients, 30 (62.5%) consented, of whom 16 (53.3%) were randomized to antibiotics-first and 14 (46.7%) to appendectomy. Median age was 33 years (range 9 to 73 years), median WBC count was 15,000/µL (range 6,200 to 23,100/µL), and median computed tomography appendiceal diameter was 10 mm (range 7 to 18 mm). Of 15 antibiotic-treated adults, 14 (93.3%) were discharged from the ED and all had symptom resolution. At 1 month, major complications occurred in 2 appendectomy participants (14.3%; 95% confidence interval [CI] 1.8% to 42.8%) and 1 antibiotics-first participant (6.3%; 95% CI 0.2% to 30.2%). Antibiotics-first participants had less total hospital time than appendectomy participants, 16.2 versus 42.1 hours, respectively. Antibiotics-first-treated participants had less pain and disability. During median 12-month follow-up, 2 of 15 antibiotics-first-treated participants (13.3%; 95% CI 3.7% to 37.9%) developed appendicitis and 1 was treated successfully with antibiotics; 1 had appendectomy. No more major complications occurred in either group. CONCLUSION: A multicenter US trial comparing antibiotics-first to appendectomy, including outpatient management, is feasible to evaluate efficacy and safety.

NONOPERATIVE MANAGEMENT OF DIFFERENTIATED THYROID CANCER IN CALIFORNIA: A POPULATION-LEVEL ANALYSIS OF 29,978 PATIENTS.

OBJECTIVE: There has been increasing interest in active surveillance of papillary thyroid microcarcinoma. The objective of this study was to characterize the incidence and outcomes of nonoperatively managed differentiated thyroid cancers (DTCs) in California. METHODS: Biopsy-proven DTCs from the California Cancer Registry were linked to data from the California Office of Statewide Health Planning and Development (2004-2012). Low-risk tumors were defined as localized disease measuring <4 cm without extrathyroidal extension, nodal involvement, or distant metastasis. RESULTS: Of 29,978 patients with DTC, 318 (1.1%) were managed nonoperatively. Compared to operatively managed patients, patients managed nonoperatively were older with more comorbidities, larger tumors (mean size, 2.9 cm vs. 2.0 cm), and an increased rate of distant metastasis (20.4% vs. 3.4%). Independent predictors of nonoperative management included increasing age, larger tumor size, papillary histology, and distant metastases. Of 10,795 patients with low-risk tumors, 161 (1.5%) were managed nonoperatively, with tumor size as follows: <1 cm (15.5%), 1 to 2 cm (50.3%), >2 to 3 cm (24.3%), and >3 to 4 cm (9.9%). There were no disease-specific deaths in the low-risk, nonoperative group (median follow-up [interquar-tile range], 21.3 [5.7 to 51.1] months). The proportion of patients managed nonoperatively remained relatively stable over the study period (mean increase 0.1% per year, P = .09). All P values were <.05 unless otherwise stated. CONCLUSION: The vast majority of patients with DTCs are treated surgically, suggesting active surveillance is rarely practiced in California. Although follow-up was limited, no disease-specific mortality in nonoperatively managed, low-risk DTCs was observed. ABBREVIATIONS: CCI = Charlson Comorbidity Index; CCR = California Cancer Registry; CI = confidence interval; DTC = differentiated thyroid cancer; FTC = follicular thyroid carcinoma; HCC = Hürthle cell carcinoma; IQR = interquartile range; mPTC = papillary thyroid micro-carcinoma; OR = odds ratio; OSPHD = Office of Statewide Health Planning and Development; PTC = papillary thyroid carcinoma.

More Extensive Surgery May Not Improve Survival Over Parathyroidectomy Alone in Parathyroid Carcinoma.

BACKGROUND: Parathyroid carcinoma is a rare cause of hyperparathyroidism. Surgery is the only effective therapy, and en bloc resection has previously been recommended. METHODS: A retrospective cohort study of patients with parathyroid carcinoma in the California Cancer Registry and California Office of Statewide Health Planning and Development database from 1999 to 2012 was performed. Patients were stratified by surgical procedure: parathyroidectomy alone, thyroid resection with en bloc parathyroidectomy, and parathyroidectomy with delayed thyroid resection within 6 months. The primary outcome was overall survival stratified by surgical procedure. Secondary outcomes included perioperative complications within 30 days of initial surgery and disease-related complications. RESULTS: Among our study cohort (n = 136), 60 patients underwent parathyroidectomy alone, 58 patients had en bloc resection, and 18 patients had parathyroidectomy followed by delayed thyroid resection. For the entire cohort, the 5-year and 10-year overall survival rates were 86.9 and 72.0 %. The overall survival rates did not differ between the surgical procedures. Factors that were independently associated with decreased survival included age (hazard ratio 1.05, P = 0.017) and distant metastases (hazard ratio 4.73, P = 0.017), while en bloc resection and delayed thyroid resection were not associated with improved survival over parathyroidectomy alone. There were no differences in perioperative or disease-related complications across procedures. CONCLUSIONS: The addition of thyroid resection to parathyroidectomy may not improve survival for patients with parathyroid carcinoma over complete parathyroid resection alone. A larger prospective study is necessary to determine the optimal treatment to achieve long-term survival with minimal complications.

Cost modeling for management strategies of uncomplicated gastroschisis.

INTRODUCTION: Compared to operative fascial closure, nonoperative flap and/or skin-closure repair for gastroschisis has several potential advantages: avoidance of anesthesia, decreased pain, and improved cosmesis. Disadvantages include a higher risk of hernia. We hypothesized that routine nonoperative closure results in cost savings versus conventional management in uncomplicated gastroschisis. METHODS: A decision tree was constructed to compare three different strategies for the management of uncomplicated gastroschisis: nonoperative closure, primary closure, and routine silo. Model variables were abstracted from a literature review and the Medicare Physician Fee schedule. Uncertainty surrounding model parameters was assessed via one-way and probabilistic sensitivity analyses. RESULTS: According to our model, the nonoperative strategy for uncomplicated gastroschisis was the least costly, with an expected cost of $198,085 per patient. Primary closure cost $208,763 per patient. Routine silo placement was the most costly, $239,038 per patient. One-way sensitivity analysis suggested the cost of primary closure would be less costly than nonoperative management if the initial success rate of nonoperative management was less than 35.4% or if the initial success rate of primary operative closure was greater than 87.8%. Probabilistic sensitivity analysis found that nonoperative management was the least costly strategy among 97.4% of 10,000 Monte Carlo simulations. CONCLUSIONS: A nonoperative strategy for uncomplicated gastroschisis with routine attempted flap and/or skin closure repair is less costly than strategies using routine primary closure and routine silo placement. Given the expected cost savings and other potential advantages of the nonoperative strategy (including avoidance of general anesthesia), more studies examining outcomes of the flap and/or skin closure are indicated.

Trends in the frequency and quality of parathyroid surgery: analysis of 17,082 cases over 10 years.

OBJECTIVE: To examine trends in the frequency and quality of surgery for primary hyperparathyroidism (PHPT) in California during the period of 1999 to 2008. BACKGROUND: The quality of surgery for PHPT can be measured by the complication rate and the success rate of surgery. A fraction of patients with failed initial surgery undergo reoperation. METHODS: Data on patients undergoing parathyroidectomy (PTx) were obtained from the California Office of Statewide Health Planning and Development. Renal transplant recipients and dialysis patients were excluded. Hospitals were categorized by case volume: Very low: 1 to 4 operations annually; Low: 5 to 9; Medium, 10 to 19; High: 20 to 49; Very high: 50 or more. Complication rates and the percentage of cases requiring reoperation were analyzed. RESULTS: A total of 17,082 cases were studied. Annual case volume grew from 990 to 2746 (177% increase) over the study period, corresponding to a 147% increase in the per capita PTx rate. The proportion of cases performed by very high-volume hospitals increased from 6.4% to 20.5% (P < 0.001). The overall complication rate declined from 8.7% to 3.8% (P < 0.001). Complication rates were inversely related to hospital volume (very high volume, 3.9% vs very low volume, 5.2%, P < 0.05). Reoperation was performed in 363 patients (2.1%). The reoperation rate increased from 0.91% to 2.73% during the study period (P < 0.01). The reoperation rate was inversely and nonlinearly related to hospital volume, as described by the equation % reoperation = 100/(total hospital case volume). CONCLUSIONS: Surgery for PHPT has grown safer and more common over time. High-volume centers have lower rates of complication and reoperation.

National Trends and Outcomes in the Operative Management of Thyroid Storm.

BACKGROUND: Thyroid storm is a rare but potentially lethal manifestation of thyrotoxicosis. Guidelines recommend nonoperative management of thyroid storm, but thyroidectomy can be performed if patients fail medical therapy or need immediate resolution of the storm. Outcomes of thyroidectomy for management of thyroid storm remain ill-defined. METHODS: Using the National Inpatient Sample from 2016 to 2020, a retrospective analysis was conducted of patients admitted with thyroid storm. Outcomes of interest included operative complications and mortality. Multivariable logistic regression was performed to assess factors associated with receiving thyroidectomy and mortality. RESULTS: An estimated 16,175 admissions had a diagnosis of thyroid storm. The incidence of thyroid storm increased from .91 per 100,000 people in 2016 to 1.03 per 100,000 people in 2020, with a concomitant increase in mortality from 2.9% to 5.3% (P < .001). Operative intervention was pursued in 635 (3.9%) cases with a perioperative complication rate of 30%. On multivariable regression, development of acute decompensated heart failure (adjusted odds ratio [AOR] 1.66, 95% Confidence Interval [CI] 1.03-2.68, P = .037) and acute renal failure (AOR 2.10, 95% CI 1.17-3.75, P = .013) increased odds of receiving surgery. The same multivariable model did not show a significant association between thyroidectomy and mortality. DISCUSSION: The incidence of thyroid storm and associated mortality increased during the study period. Thyroidectomy is rarely performed during the same admission, with an overall perioperative complication rate of 30% and no effect on mortality. Patients with acute decompensated heart failure and renal failure were more likely to receive an operative intervention.

Rural-Urban Disparities in the Continuum of Thyroid Cancer Care: Analysis of 92,794 Cases.

Objective: Rurality is associated with higher incidence and higher disease-specific mortality for most cancers. Outcomes for rural and ultrarural ("frontier") patients with thyroid cancer are poorly understood. This study aimed to identify actionable deficits in thyroid cancer outcomes for rural patients. Methods: We queried linked California Cancer Registry and California Office of Statewide Health Planning and Development databases for patients diagnosed with thyroid cancer (1999-2017). We analyzed time from disease stage at diagnosis, time from diagnosis to surgery, receipt of appropriate radioactive iodine ablation, surveillance status, and overall and disease-specific mortality for urban, rural, and frontier patients. Cox and logistic regression models controlled for clinical and demographic covariates a stepwise manner. All incidence figures are expressed as a proportion of newly diagnosed cases. Results: Our cohort comprised 92,794 subjects: (65,475 women [70.6%]; mean age 50.0 years). Compared to urban patients, rural and frontier patients were more likely to be American Indian, White, uninsured, and from lower quintiles of socioeconomic status (p < 0.01). Distant disease at diagnosis was more common in rural (56.0 vs. 50.4 cases per 1000 new cases, p < 0.01) and frontier patients (80.9 vs. 50.4 per 1000, p < 0.01) compared to urban patients. The incidence of medullary thyroid cancer was greater in rural patients (17.9 vs. 13.6 cases per 1000, p < 0.01) and frontier patients (31.0 vs. 13.6 per 1000, p < 0.01) compared to urban patients. The incidence of anaplastic thyroid cancer was higher in frontier versus urban patients (15.5 vs. 7.1 per 1000, p < 0.01). When compared to urban patients, rural and frontier patients were more often lost to follow-up (odds ratio [OR] 1.69 [confidence interval, CI 1.54-1.85], and OR 3.03 [CI 1.89-5.26], respectively) and had higher disease-specific mortality (OR 1.18 [CI 1.07-1.30], and OR 1.92 [CI 1.22-2.77], respectively). Rural and frontier residence was independently associated with being lost to follow-up, suggesting that it is a key driver of disparities. Conclusion: Compared to their urban counterparts, rural and frontier patients with thyroid cancer present with later-stage disease and experience higher disease-specific mortality. They also are more often lost to follow-up, which presents an opportunity for targeted outreach to reduce the observed disparities in outcomes.

Diagnostic performance of molecular testing in indeterminate (Bethesda III and IV) thyroid nodules with Hürthle cell cytology.

BACKGROUND: Indeterminate thyroid nodules with Hürthle cell cytology remain a diagnostic challenge. The low benign call rate and positive predictive value of first-generation molecular tests precluded their use to rule out malignancy. We examined the diagnostic performance of current tests. METHOD: This subset analysis of our prospective randomized trial compared the benign call rate and positive predictive value of Afirma Gene Sequencing Classifier and Thyroseq v3 in Bethesda III and IV nodules with Hürthle cell cytology. Molecular test samples were obtained at initial fine-needle aspiration (8/2017-7/2022) and reflexively sent for processing. RESULTS: Molecular testing was performed on 140 Hürthle cell nodules. Of 79 nodules tested with the Afirma Gene Sequencing Classifier, the benign call rate was 84% (66/79). Nine of 66 nodules with benign results were resected, with no malignancies. Twelve of 13 nodules with suspicious results were resected, revealing 3 malignancies-2 papillary thyroid carcinomas and one Hürthle cell carcinoma (positive predictive value 25%). Of 61 nodules tested with Thyroseq v3, the benign call rate was 56% (34/61; (P < .01 versus Afirma Gene Sequencing Classifier). Five of 34 nodules with negative results were resected, with no malignancies. Nineteen of 27 nodules with positive results were resected, revealing 3 malignancies-2 papillary thyroid carcinomas and 1 Hürthle cell carcinoma (positive predictive value 16%). CONCLUSION: The high benign call rate of current molecular tests in Hürthle cell nodules strengthens their value in enabling patients to avoid surgery.

Extent of Surgery for Medullary Thyroid Cancer and Prevalence of Occult Contralateral Foci.

Importance: Standard treatment for patients with medullary thyroid cancer (MTC) consists of total thyroidectomy with central neck dissection, but the rationale for bilateral surgery in patients with unilateral disease on ultrasonography remains unclear. Objective: To determine the presence of occult contralateral disease (lesions not seen on preoperative ultrasonography) in patients with MTC as a rationale for total thyroidectomy. Design, Setting, and Participants: This multi-institutional, retrospective cohort study was conducted from September 1998 to April 2022 in academic medical centers and included patients with MTC who underwent thyroidectomy with preoperative imaging. Main Outcomes and Measures: The primary end point was the prevalence of sonographically occult foci of MTC in the contralateral lobe among patients with sporadic MTC. Results: The cohort comprised 176 patients with a median age at diagnosis of 55 years (range, 2-87 years), 69 (57.6%) of whom were female. Genetic testing was performed in 109 patients (61.9%), 48 (27.5%) of whom carried germline RET variants. Initial surgical management consisted of total thyroidectomy (161 [91.0%]), lobectomy followed by completion thyroidectomy (7 [4.0%]), and lobectomy alone (8 [4.5%]). Central and lateral neck dissections were performed as part of initial therapy for 146 patients (83.1%). In the entire cohort of 176 patients, 46 (26.0%) had contralateral foci disease and 9 (5.1%) had occult contralateral foci that were not identified on preoperative ultrasonography. Among 109 patients who underwent genetic testing, 38 (34.9%) had contralateral disease, 8 (7.3%) of whom had occult contralateral disease not seen on preoperative ultrasonography. Patients with sporadic MTC experienced a 95.7% reduction in the odds of having a focus of MTC in the contralateral lobe compared with patients with a germline RET variant (odds ratio, 0.043; 95% CI, 0.013-0.123). When adjusting for age, sex, tumor size, and lymph node involvement, the odds ratio of having contralateral MTC in patients with sporadic disease was 0.034 (95% CI, 0.007-0.116). Among patients who underwent lobectomy alone with postoperative calcitonin levels, 5 of 12 (41.7%) achieved undetectable calcitonin levels (<2.0 pg/mL; to convert to pmol/L, multiply by 0.292). Conclusions and Relevance: The results of this cohort study suggest that a staged approach involving initial thyroid lobectomy could be considered in patients with sporadic MTC and no contralateral ultrasonography findings, with no further surgery if calcitonin levels became undetectable. Further work using prospective randomized clinical trials to evaluate lobectomy as a biochemical cure in patients presenting with unilateral disease is warranted.

From Bench-to-Bedside: How Artificial Intelligence is Changing Thyroid Nodule Diagnostics, a Systematic Review.

CONTEXT: Use of artificial intelligence (AI) to predict clinical outcomes in thyroid nodule diagnostics has grown exponentially over the past decade. The greatest challenge is in understanding the best model to apply to one's own patient population, and how to operationalize such a model in practice. EVIDENCE ACQUISITION: A literature search of PubMed and IEEE Xplore was conducted for English-language publications between January 1, 2015 and January 1, 2023, studying diagnostic tests on suspected thyroid nodules that used AI. We excluded articles without prospective or external validation, nonprimary literature, duplicates, focused on nonnodular thyroid conditions, not using AI, and those incidentally using AI in support of an experimental diagnostic outside standard clinical practice. Quality was graded by Oxford level of evidence. EVIDENCE SYNTHESIS: A total of 61 studies were identified; all performed external validation, 16 studies were prospective, and 33 compared a model to physician prediction of ground truth. Statistical validation was reported in 50 papers. A diagnostic pipeline was abstracted, yielding 5 high-level outcomes: (1) nodule localization, (2) ultrasound (US) risk score, (3) molecular status, (4) malignancy, and (5) long-term prognosis. Seven prospective studies validated a single commercial AI; strengths included automating nodule feature assessment from US and assisting the physician in predicting malignancy risk, while weaknesses included automated margin prediction and interobserver variability. CONCLUSION: Models predominantly used US images to predict malignancy. Of 4 Food and Drug Administration-approved products, only S-Detect was extensively validated. Implementing an AI model locally requires data sanitization and revalidation to ensure appropriate clinical performance.