Non-Operative, Active Surveillance of Larger Malignant and Suspicious Thyroid Nodules.

CONTEXT: Active surveillance for papillary thyroid cancer (PTC) meeting criteria for surgical resection is uncommon. Which patients may prove reasonable candidates for this approach is not well defined. OBJECTIVE: To examine the feasibility and safety of active surveillance for patients with known or suspected intrathyroidal PTC up to 4cm in diameter. DESIGN, SETTING, AND PARTICIPANTS: Retrospective review of all consecutive patients who underwent non-operative active surveillance of suspicious or malignant thyroid nodules over a 20-year period from 2001-2021. We included patients with an initial US-FNA confirming either: a) Bethesda 5 or 6 cytology or, b) a "suspicious" AFIRMA molecular test. The primary outcomes and measures included the rate of adverse oncologic outcomes (mortality and recurrence), as well as the cumulative incidence of size/volume growth. RESULTS: Sixty-nine patients were followed with active surveillance for 1 year or longer (average 55 months), with 26 patients (38%) having nodules ≥ 2 cm. No patients were found to develop new incident occurrence of lymph node or distant metastasis. One patient however, demonstrated concern for progression to a dedifferentiated cancer on repeat core biopsy 17 years after initial start non-operative selection. 21% of patients had an increase in maximum diameter more than 3 mm, and volume increase ≥50% was noted in 25% of patients. Thirteen patients ultimately underwent delayed (rescue) surgery, and no disease recurrence was noted after such treatment. Age and initial nodule size were not predictors of nodule growth. CONCLUSIONS: These data expand consideration of active surveillance of papillary thyroid carcinoma in select patients with intrathyroidal suspected malignancy >1cm in diameter. Rescue surgery, if required at a later timepoint, appears effective.

Practical Guide to Experimental and Quasi-Experimental Research in Surgical Education.

This Guide to Statistics and Methods describes the methods and pitfalls of experimental and quasi-experimental study designs in surgical education.

Practical Guide to Pragmatic Clinical Trials in Surgical Education Research.

This Guide to Statistics and Methods provides an overview of the key features of pragmatic trials within the context of surgical education research using examples from the Flexibility in Duty-Hour Requirements for Surgical Trainees trial.

Behavioral Interventions on Surgeons' Preoperative Decision-Making: A Scoping Review and Critical Analysis.

INTRODUCTION: Consensus is lacking regarding the optimal strategy to influence surgeons' behaviors to reduce low-value surgical care. Comprehensively describing the existing body of literature that seeks to intervene on surgeons' preoperative decision-making may aid in structuring future behavior change strategies. METHODS: We performed a scoping review using four databases (Medical Literature Analysis and Retrieval System Online, Embase, Web of Science, and Cumulated Index to Nursing and Allied Health Literature) for articles that tested the effect of behavioral-based interventions on any aspect of surgeons' decision-making in the preoperative setting. Abstracted data were characterized by summative descriptions and analyzed using the Tailored Implementation for Chronic Disease framework, mapping aspects of deimplementation strategies in the studies onto the determinant(s) that they altered. Data abstraction and mapping tools were piloted and iteratively revised before two researchers independently assessing studies and categorizing determinants, and then meeting to discuss their decisions. RESULTS: There were 1460 articles identified from the initial search, with 17 full text articles ultimately included in the scoping review. Eight studies relied on a multidisciplinary preoperative conference to accomplish their aims, while five were multifaceted in their approach to deimplementation, and four studies used only a clinical decision support tool to accomplish their aims. Mapping determinants addressed in these studies onto the Tailored Implementation for Chronic Disease framework demonstrated that most strategies attempted to close knowledge gaps, leverage communication between providers, and broadcast institutional prioritization of change. CONCLUSIONS: There is a small but growing field of implementation and deimplementation strategies in preoperative surgical decision-making, and different approaches may be equally effective in varied clinical contexts. Deliberate measurement and comparison of outcomes, as well as selection of control groups, are areas for improvement in future work.

Impact of Obesity on Risk of Hypocalcemia After Total Thyroidectomy: Targeted National Surgical Quality Improvement Program Analysis of 16,277 Patients.

INTRODUCTION: Hypocalcemia following total thyroidectomy (TT) is common due to postoperative parathyroid dysfunction and vitamin D deficiency. Given the association between obesity and vitamin D deficiency, we sought to correlate body mass index (BMI) with hypocalcemia after TT. METHODS: Patients undergoing TT between 2016 and 2020 were identified from the American College of Surgeons National Surgical Quality Improvement Program thyroidectomy-targeted database. Univariable and multivariable regressions, stratified by BMI category (normal, overweight, obese), identified factors associated with hypocalcemia prior to discharge, within 30 d, and severe hypocalcemic events (emergent evaluation, intravenous calcium supplementation, or readmission). RESULTS: Sixteen thousand two hundred seventy seven TT were performed with available BMI data. Three thousand five hundred thirty one (21.7%) patients had normal BMI, 4823 (29.6%) were overweight, and 7772 (47.7%) were obese. Patients with BMI ≥ 25 had decreased risk of hypocalcemia before discharge (9.8% versus 13%, odds ratio [OR] 0.73, P < 0.001), 30 d (8.1% versus 10.4%, OR 0.76, P < 0.001), and severe hypocalcemic events (5.5% versus 6.4%, OR 0.84, P = 0.029) compared to normal BMI patients. On multivariable analysis for normal BMI patients, age < 45 y was a risk factor for hypocalcemia before discharge, 30 d, and severe hypocalcemic events (P < 0.05 for all). Additional risk factors in this group for 30-d hypocalcemia included parathyroid autotransplant and central neck dissection (P < 0.05) and recurrent laryngeal nerve injury for severe hypocalcemic events (P = 0.01). CONCLUSIONS: Younger patients with BMI < 25 are at an increased risk for hypocalcemia and severe hypocalcemic events after TT. These patients may benefit from preoperative counseling and increased calcium/vitamin D supplementation to reduce prolonged hospitalization and mitigate morbidity.

Additional Oncogenic Alterations in RAS-Driven Differentiated Thyroid Cancers Associate with Worse Clinicopathologic Outcomes.

PURPOSE: RAS mutations occur across the spectrum of thyroid neoplasms, and more tools are needed for better prognostication. The objective of this study was to evaluate how additional genetic events affecting key genes modify prognosis in patients with RAS-mutant thyroid cancers, and specifically differentiated thyroid cancers (DTC). EXPERIMENTAL DESIGN: We performed a clinical-genomic analysis of consecutive patients with DTC, poorly differentiated (PDTC), or anaplastic thyroid cancer (ATC) between January 2014 and December 2021, in whom a custom-targeted next-generation sequencing assay was performed. Patients harboring RAS mutations were included, and we compared their clinical features and outcomes based upon the presence of additional oncogenic alterations. RESULTS: Seventy-eight patients were identified, with 22% (17/78) harboring a driver RAS mutation plus an additional oncogenic alteration. All six (100%) ATCs had an additional mutation. Compared with DTCs harboring a solitary RAS mutation, patients with DTC with RAS and additional mutation(s) were more likely to be classified as American Thyroid Association high-risk of recurrence (77% vs. 12%; P < 0.001) and to have larger primary tumors (4.7 vs. 2.5 cm; P = 0.002) and advanced stage (III or IV) at presentation (67% vs. 3%; P < 0.001). Importantly, over an average 65-month follow-up, DTC-specific-mortality was more than 10-fold higher (20% vs. 1.8%; P = 0.011) when additional mutations were identified. CONCLUSIONS: Identification of key additional mutations in patients with RAS-mutant thyroid cancers confers a more aggressive phenotype, increases mortality risk in DTC, and can explain the diversity of RAS-mutated thyroid neoplasia. These data support genomic profiling of DTCs to inform prognosis and clinical decision-making.

Higher SUVmax on FDG-PET is associated with shorter survival in adrenocortical carcinoma.

BACKGROUND: Adrenocortical carcinoma (ACC) is an aggressive, rare malignancy. 2-deoxy-2-[18F]-fluoro-d-glucose positron emission tomography (FDG-PET) assesses tumor metabolism and glucose utilization. We hypothesized that higher maximum standard uptake value (SUVmax) is associated with decreased survival. METHODS: We performed a retrospective analysis of patients with ACC. Included patients (n = 26) had an FDG-PET scan available with a documentable SUVmax. Patients were dichotomized into "High" (≥8.4, n = 12) and "Low" (<8.4, n = 14) SUVmax. Univariate analysis and survival analysis were performed to compare groups. RESULTS: Demographics between groups were equivalent. The high SUVmax cohort demonstrated lower survival (median 479 days or 15.7 months) compared to the low group (median 1490 days or 48.6 months, p = .01). Log-Rank curve confirmed differences in survival (p = .007). CONCLUSIONS: Higher SUVmax was associated with significantly worse survival in ACC and may reflect a more aggressive phenotype. FDG-PET may provide clinically useful information to determine prognosis and treatment. Further studies should prospectively evaluate using FDG-PET/CT in ACC.

Understanding Hospital-Level Patterns of Nonoperative Management for Low-risk Thyroid and Kidney Cancer.

Importance: There is a growing trend toward conservative management for certain low-risk cancers. Hospital and health-system factors may play a role in determining how these patients are managed. Objective: To explore the contribution of hospitals on patients' odds of nonoperative management for low-risk cancer. Design, Setting, and Participants: In this cross-sectional study, individuals with low-risk papillary thyroid cancer and solitary kidney masses were identified, and those receiving nonoperative management vs surgery were compared. Patients with low-risk thyroid cancer and kidney cancer from 2015 to 2017 eligible for nonoperative management according to National Comprehensive Cancer Network guidelines within the National Cancer Database were included. Data were analyzed from October 2021 to March 2022. Main Outcomes and Measures: For each facility, the proportion of these patients who received operative and nonoperative management was calculated. A mixed-effects logistic regression model with a hospital-level random effects term was used to calculate factors associated with nonoperative management. Between-hospital variability was assessed using ranked caterpillar plots. Results: There were 19 570 individuals with low-risk thyroid cancer (15 344 women [78.4%]; mean [SD] age, 51.74 [95% CI, 51.39-52.08] years) and 41 403 with kidney cancer (25 253 men [61.0%]; mean [SD] age, 61.93 [95% CI, 61.70-62.17] years). In the group with low-risk thyroid cancer, 2.1% (419 patients) received nonoperative management, and in the group with kidney cancer, 9.5% (3928 patients) received nonoperative management. This varied between hospitals from 1.1% (95% CI, 1.0%-1.1%) in the bottom decile to 10.3% (95% CI, 8.0%-12.4%) in the top decile for low-risk thyroid cancer, and from 4.3% (95% CI, 4.1%-4.4%) in the bottom decile to 24.6% (95% CI, 22.7%-26.5%) in the top decile for small kidney masses. For both cancers, age was associated with increased odds of nonoperative treatment. The hospital-level odds of nonoperative management of thyroid and kidney cancer using unadjusted probabilities (observed proportions) were minimally correlated (Spearman ρ = .33; P < .001). Conclusions and Relevance: The findings of this study suggest that although health systems factors may be associated with the tendency to pursue nonoperative management, hospital-level factors may differ when comparing unrelated cancers.

Increased Body Mass Index is Associated With Lower Risk of Hypocalcemia in Total Thyroidectomy Patients.

INTRODUCTION: Hypocalcemia following total thyroidectomy is common due to postoperative parathyroid dysfunction. We sought to identify the impact of obesity on postthyroidectomy hypocalcemia. METHODS: We performed a single-center retrospective study of all total thyroidectomies performed from 2016 to 2019 after implementation of an updated calcium supplementation protocol. Patient characteristics and outcomes were measured including body mass index (BMI), postoperative hypocalcemia (Ca <8.3), and hypocalcemic symptoms. RESULTS: Overall, 559 total thyroidectomies were performed. A total of 146 patients (26.2%) developed hypocalcemia requiring supplementation adjustment and 116 patients (20.8%) developed mild hypocalcemia symptoms. On multivariable analysis, younger patients, patients with lower preoperative calcium, and lower BMI were more likely to develop postoperative hypocalcemia (all P < 0.05). Similarly, younger patients and patients with BMI <25 were more likely to develop hypocalcemic symptoms (all P < 0.05). CONCLUSIONS: Younger age and lower BMI were associated with increased risk of hypocalcemia after total thyroidectomy. These patients may benefit from preoperative and/or increased postoperative supplementation.

Management of thyroid nodules.

In the past 30 years, there has been a substantial rise in the detection of thyroid nodules. Largely asymptomatic, thyroid nodules are most often incidental findings that typically pose minimal risk. Data supporting these findings show a rapid rise in the incidental detection of thyroid nodules and cancer, but minimal effect on mortality rates, despite treatment. These data imply that historical approaches to thyroid nodule and cancer care might at times include unnecessary or excessive care. To address this issue, the past decade has witnessed an increasingly conservative approach to nodule management, seeking to individualise care and provide the most focused intervention that leads to favourable outcomes. Benign nodules can be safely monitored with minimal, or long-interval follow-up imaging. Molecular testing should be considered for cytologically indeterminate nodules because of its ability to improve preoperative cancer risk determination and reduce unnecessary surgery. The treatment of biopsy-proven malignant nodules has become increasingly nuanced, since recommendations for near-total thyroidectomy are no longer routine. Hemithyroidectomy is now commonly considered when operative intervention is favoured. Some patients with small volume, isolated cancerous nodules are safely managed non-operatively with active monitoring. In summary, modern management strategies for thyroid nodular disease seek to incorporate the growing amount of available diagnostic and prognostic data, inclusive of demographic, radiological, pathological and molecular findings. Once obtained, an individualised management plan can be effectively formulated.

Surgical Management of Gastric Cancer: A Review.

Importance: Surgery plays a critical role in the management of all stages of gastric cancer. Observations: For patients with early gastric cancer and low risk of lymph node metastasis, endoscopic therapy or surgery alone is potentially curative. Novel techniques, such as sentinel lymph node biopsy, may allow for greater use of stomach-sparing procedures that could improve quality of life without compromising oncologic outcomes; however, experience with these techniques is rare outside of East Asia, and studies of long-term outcomes are still ongoing. Patients with later-stage localized gastric cancer benefit from more extensive lymphadenectomy and multimodality therapy, as they are at risk for nodal and distant metastases. There have been recent advances in chemotherapy that have led to improved survival, but the optimal sequencing of multimodality therapy is still being investigated. Better systemic therapy may also increase the role of surgery for patients with oligometastatic disease. There are ongoing studies examining the efficacy of peritoneal-directed therapies in both patients with low-volume peritoneal disease and patients at high risk of peritoneal recurrence. Conclusions and Relevance: The management of gastric cancer continues to evolve. Surgeons should be aware of novel surgical approaches currently under investigation as well as how surgery fits into the contemporary multidisciplinary approach to this disease.

The Need for Standardizing Diagnosis, Treatment and Clinical Care of Cholecystitis and Biliary Colic in Gallbladder Disease.

Gallstones affect 20% of the Western population and will grow in clinical significance as obesity and metabolic diseases become more prevalent. Gallbladder removal (cholecystectomy) is a common treatment for diseases caused by gallstones, with 1.2 million surgeries in the US each year, each costing USD 10,000. Gallbladder disease has a significant impact on the logistics and economics of healthcare. We discuss the two most common presentations of gallbladder disease (biliary colic and cholecystitis) and their pathophysiology, risk factors, signs and symptoms. We discuss the factors that affect clinical care, including diagnosis, treatment outcomes, surgical risk factors, quality of life and cost-efficacy. We highlight the importance of standardised guidelines and objective scoring systems in improving quality, consistency and compatibility across healthcare providers and in improving patient outcomes, collaborative opportunities and the cost-effectiveness of treatment. Guidelines and scoring only exist in select areas of the care pathway. Opportunities exist elsewhere in the care pathway.

Oncogenic Mutations in PI3K/AKT/mTOR Pathway Effectors Associate with Worse Prognosis in BRAFV600E -Driven Papillary Thyroid Cancer Patients.

PURPOSE: The extent to which routine genomic sequencing can identify relevant secondary genomic alterations among BRAFV600E -mutant papillary thyroid carcinoma (PTC) is unknown. Such markers would prove highly valuable for prognostic purposes. EXPERIMENTAL DESIGN: We reviewed clinicopathologic data of 225 patients with BRAFV600E -mutant PTC and integrated them with genomic data derived from targeted next-generation sequencing (NGS) on tumor specimens. We defined patient subgroups based on bona fide secondary oncogenic events (separate from BRAFV600E ) and compared their clinical features and outcomes with those without additional oncogenic alterations. RESULTS: Additional oncogenic alterations were identified in 16% of tumors. Patients in the "BRAF+additional mutations" group were more likely to be at high American Thyroid Association (ATA) risk of recurrence (48.6% vs. 17.6%; P = 0.0009), had larger baseline tumor (2.7 vs. 1.9 cm; P = 0.0005) and more advanced stage at presentation (14.3% vs. 1.1% stage 4; P < 0.0001). Importantly, over a 65-month follow-up, disease-specific mortality (DSM) was increased when additional mutations were identified (13.8% vs. 1.4% in the BRAF-only group; P = 0.005). Separately, we identified a subcluster of patients harboring oncogenic mutations in key effectors of the PI3K/AKT/mTOR pathway, which were independently associated with DSM (OR = 47.9; 95% confidence interval, 3.5-1,246.5; P = 0.0043). CONCLUSIONS: Identification of additional PIK3/AKT/mTOR alterations in patients with BRAFV600E -mutant PTC provides important and actionable prognostic risk stratification. These data support genomic profiling of PTC tumors to inform prognosis and clinical strategy.