Management of Pheochromocytomas and Paragangliomas.

Pheochromocytomas and paragangliomas are distinctive neuroendocrine tumors which frequently produce excess catecholamines with resultant cardiovascular morbidity. These tumors have a strong genetic component, with up to 40% linked to hereditary pathogenic variants; therefore, germline genetic testing is recommended for all patients. Surgical resection offers the only potential cure in the case of localized disease. Given the potential for catecholaminergic crises, appropriate perioperative management is crucial, and all patients should undergo alpha-adrenergic blockade before resection. Therapeutic options for metastatic disease are limited and include surgical debulking, radiopharmaceutical therapies, and conventional chemotherapy.

Surgeon and Surgical Trainee Experiences After Adverse Patient Events.

Importance: Adverse patient events are inevitable in surgical practice. Objectives: To characterize the impact of adverse patient events on surgeons and trainees, identify coping mechanisms, and assess whether current forms of support are sufficient. Design, Setting, and Participants: In this mixed-methods study, a validated survey instrument was adapted and distributed to surgical trainees from 7 programs, and qualitative interviews were conducted with faculty from 4 surgical departments in an urban academic health system. Main Outcomes and Measures: The personal impact of adverse patient events, current coping mechanisms, and desired forms of support. Results: Of 216 invited trainees, 93 (43.1%) completed the survey (49 [52.7%] male; 60 [64.5%] in third postgraduate year or higher; 23 [24.7%] Asian or Pacific Islander, 6 [6.5%] Black, 51 [54.8%] White, and 8 [8.6%] other race; 13 [14.0%] Hispanic or Latinx ethnicity). Twenty-three of 29 (79.3%) invited faculty completed interviews (13 [56.5%] male; median [IQR] years in practice, 11.0 [7.5-20.0]). Of the trainees, 77 (82.8%) endorsed involvement in at least 1 recent adverse event. Most reported embarrassment (67 of 79 trainees [84.8%]), rumination (64 of 78 trainees [82.1%]), and fear of attempting future procedures (51 of 78 trainees [65.4%]); 28 of 78 trainees (35.9%) had considered quitting. Female trainees and trainees who identified as having a race and/or ethnicity other than non-Hispanic White consistently reported more negative consequences compared with male and White trainees. The most desired form of support was the opportunity to discuss the incident with an attending physician (76 of 78 respondents [97.4%]). Similarly, faculty described feelings of guilt and shame, loss of confidence, and distraction after adverse events. Most described the utility of confiding in peers and senior colleagues, although some expressed unwillingness to reach out. Several suggested designating a departmental point person for event debriefing. Conclusions and Relevance: In this mixed-methods study of the personal impact of adverse events on surgeons and trainees, these events were nearly universally experienced and caused significant distress. Providing formal support mechanisms for both surgical trainees and faculty may decrease stigma and restore confidence, particularly for underrepresented groups.

Revisiting the Relationship Between Tumor Size and Risk in Well-Differentiated Thyroid Cancer.

Introduction: Large tumor size is associated with poorer outcomes in well-differentiated thyroid cancer, yet it remains unclear whether size >4 cm alone confers increased risk, independent of other markers of aggressive disease. The goal of this study was to assess the relationship between tumor size, other high-risk histopathological features, and survival in well-differentiated thyroid cancer and to evaluate the significance of 4 cm as a cutoff for management decisions. Methods: Patients with well-differentiated thyroid cancer were identified from the National Cancer Database (2010-2015) and categorized by tumor size (i.e., small [≤4 cm] or large [>4 cm]) and presence of high-risk histopathological features (e.g., extrathyroidal extension). First, propensity score matching was used to identify patients who were similar across all other observed characteristics except for small versus large tumor size, and a multivariable Cox proportional hazards model was used to estimate the relationship between tumor size and survival. Second, we assessed whether the presence of high-risk features demonstrates conditional effects on survival based on the presence of tumor size >4 cm using an interaction term. Finally, additional models assessed the relationship between incremental 1 cm increases in tumor size and survival. Analyses were repeated using a validation cohort from the Surveillance, Epidemiology, and End Results Program (2008-2013). Results: Of 193,133 patients in the primary cohort, 7.9% had tumors >4 cm, and 30% had at least one high-risk feature. After matching, tumor size >4 cm was independently associated with worse survival (HR 1.63, p < 0.001). However, tumor size >4 cm and one or more other high-risk features together yielded worse survival than either size >4 cm alone (MMD: 0.70, p < 0.001) or other high-risk features alone (MMD: 0.49, p < 0.001). When assessed in 1 cm increments, the largest increases in hazard of death occurred at 2 cm and 5 cm, not 4 cm. Results from the validation cohort were largely consistent with our primary findings. Conclusions: Concomitant high-risk features confer worse survival than large tumor size alone, and a 4 cm cutoff is not associated with the greatest increase in risk. These findings support a more nuanced approach to tumor size in the management of well-differentiated thyroid cancer.

Antihypertensive Medication Use Trajectories After Bariatric Surgery: A Matched Cohort Study.

BACKGROUND: Metabolic and bariatric surgery (MBS) is the most effective and durable treatment for obesity. We aimed to compare the trajectories of antihypertensive medication (AHM) use among obese individuals treated and not treated with MBS. METHODS: Adults with a body mass index of ≥35 kg/m2 were identified in the Merative Database (US employer-based claims database). Individuals treated with versus without MBS were matched 1:1 using baseline demographic and clinical characteristics as well as AHM utilization. Monthly AHM use was examined in the 3 years after the index date using generalized estimating equations. Subanalyses investigated rates of AHM discontinuation, AHM initiation, and apparent treatment-resistant hypertension. RESULTS: The primary cohort included 43 206 adults who underwent MBS matched with 43 206 who did not. Compared with no MBS, those treated with MBS had sustained, markedly lower rates of AHM use (31% versus 15% at 12 months; 32% versus 17% at 36 months). Among patients on AHM at baseline, 42% of patients treated with MBS versus 7% treated medically discontinued AHM use (P<0.01). The risk of apparent treatment-resistant hypertension was 3.41× higher (95% CI, 2.91-4.01; P<0.01) 2 years after the index date in patients who did not undergo MBS. Among those without hypertension treated with MBS versus no MBS, 7% versus 21% required AHM at 2 years. CONCLUSIONS: MBS is associated with lower rates of AHM use, higher rates of AHM discontinuation, and lower rates of AHM initiation among patients not taking AHM. These findings suggest that MBS is both an effective treatment and a preventative measure for hypertension.

Collaborative Development and Implementation of a Hybrid Virtual Surgery Clerkship Curriculum in a Vietnamese Medical School.

OBJECTIVE: To collaboratively develop a hybrid virtual curriculum for a medical school surgery clerkship within an emerging medical university in Vietnam. DESIGN: A hybrid virtual surgery clerkship curriculum was collaboratively developed by Vietnamese and American surgeons as part of an international partnership between their respective universities. A set of 25 virtual lectures with associated materials were created and deployed in tandem with live, in-person review and skills sessions. Student quantitative and qualitative evaluation methods were developed and deployed to allow continuous iteration. A 6-month course was deployed to develop surgical faculty into effective teachers. SETTING: The curriculum was deployed at VinUniversity College of Health Sciences, the youngest medical university in Vietnam. It was developed in collaboration with the University of Pennsylvania Perelman School of Medicine. Each cohort of 12 students in the surgical clerkship will participate in the curriculum. CONCLUSIONS: The development of this hybrid surgical clerkship in Vietnam leveraged local resources and expertise with those available remotely. Lessons learned are directly applicable to future collaborative curriculum development efforts at other emerging medical schools.

Surgical Management of Metastatic Adrenocortical Carcinoma.

Introduction: Adrenocortical carcinoma (ACC) is a notoriously aggressive cancer with a dismal prognosis, especially for patients with metastatic disease. Metastatic ACC is classically a contraindication to operative management. Here, we evaluate the impact of primary tumor resection and metastasectomy on survival in metastatic ACC. Methods: We performed a retrospective cohort study of patients with metastatic ACC (2010-2019) utilizing the National Cancer Database. The primary outcome was overall survival (OS). Cox proportional hazards models were developed to evaluate the associations between surgical management and survival. Propensity score matching (PSM) was utilized to account for selection bias in receipt of surgery. Results: Of 976 subjects with metastatic ACC, 38% underwent surgical management. Median OS across all patients was 7.6 months. On multivariable Cox proportional hazards regression, primary tumor resection alone (HR: 0.523; p<0.001) and primary resection with metastasectomy (HR: 0.372; p<0.001) were significantly associated with improved OS. Metastasectomy alone had no association with OS (HR: 0.909; p=0.740). Primary resection with metastasectomy was associated with improved OS over resection of the primary tumor alone (HR: 0.636; p=0.018). After PSM, resection of the primary tumor alone remained associated with improved OS (HR 0.593; p<0.001), and metastasectomy alone had no survival benefit (HR 0.709; p=0.196) compared with non-operative management; combined resection was associated with improved OS over primary tumor resection alone (HR 0.575, p=0.008). Conclusion: In metastatic ACC, patients may benefit from primary tumor resection alone or in combination with metastasectomy, however further research is required to facilitate appropriate patient selection.

Sex differences and racial/ethnic disparities in the presentation and treatment of medullary thyroid cancer.

BACKGROUND: This study assessed for disparities in the presentation and management of medullary thyroid cancer (MTC). METHODS: Patients with MTC (2010-2020) were identified from the National Cancer Database. Differences in disease presentation and likelihood of guideline-concordant surgical management (total thyroidectomy and resection of ≥1 lymph node) were assessed by sex and race/ethnicity. RESULTS: Of 6154 patients, 68.2% underwent guideline-concordant surgery. Tumors >4 â€‹cm were more likely in men (vs. women: OR 2.47, p â€‹< â€‹0.001) and Hispanic patients (vs. White patients: OR 1.52, p â€‹= â€‹0.001). Non-White patients were more likely to have distant metastases (Black: OR 1.63, p â€‹= â€‹0.002; Hispanic: OR 1.44, p â€‹= â€‹0.038) and experienced longer time to surgery (Black: HR 0.66, p â€‹< â€‹0.001; Hispanic: HR 0.71, p â€‹< â€‹0.001). Black patients were less likely to undergo guideline-concordant surgery (OR 0.70, p â€‹= â€‹0.022). CONCLUSIONS: Male and non-White patients with MTC more frequently present with advanced disease, and Black patients are less likely to undergo guideline-concordant surgery.

Adrenalectomy approach and outcomes according to surgeon volume.

BACKGROUND: This study assessed the relationship between surgeon volume, operative management, and resource utilization in adrenalectomy. METHODS: Isolated adrenalectomies performed within our health system were identified (2016-2021). High-volume surgeons were defined as those performing ≥6 cases/year. Outcomes included indication for surgery, perioperative outcomes, and costs. RESULTS: Of 476 adrenalectomies, high-volume surgeons (n â€‹= â€‹3) performed 394, while low-volume surgeons (n â€‹= â€‹12) performed 82. High-volume surgeons more frequently operated for pheochromocytoma (19% vs. 16%, p â€‹< â€‹0.001) and less frequently for metastasis (6.4% vs. 23%, p â€‹< â€‹0.001), more frequently used laparoscopy (95% vs. 80%, p â€‹< â€‹0.001), and had lower operative supply costs ($1387 vs. $1,636, p â€‹= â€‹0.037). Additionally, laparoscopic adrenalectomy was associated with shorter length of stay (-3.43 days, p â€‹< â€‹0.001), lower hospitalization costs (-$72,417, p â€‹< â€‹0.001), and increased likelihood of discharge to home (OR 17.03, p â€‹= â€‹0.008). CONCLUSIONS: High-volume surgeons more often resect primary adrenal pathology and utilize laparoscopy. Laparoscopic adrenalectomy is, in turn, associated with decreased healthcare resource utilization.

Defining Optimal Management of Non-metastatic Adrenocortical Carcinoma.

BACKGROUND: Adrenocortical carcinoma (ACC) is an aggressive, deadly malignancy. Resection remains the primary treatment; however, there is conflicting evidence regarding the optimal approach to and extent of surgery and the role of adjuvant therapy. We evaluated the impact of surgical technique and adjuvant therapies on survival in non-metastatic ACC. METHODS: We performed a retrospective cohort study of subjects who underwent surgery for non-metastatic ACC between 2010 and 2019 utilizing the National Cancer Database. The primary outcome was overall survival. Cox proportional hazards models were developed to identify associations between clinical and treatment characteristics and survival. RESULTS: Overall, 1175 subjects were included. Their mean age was 54 ± 15 years, and 62% of patients were female. 67% of procedures were performed via the open approach, 22% involved multi-organ resection, and 26% included lymphadenectomy. Median survival was 77.1 months. Age (hazard ratio [HR] 1.019; p < 0.001), advanced stage (stage III HR 2.421; p < 0.001), laparoscopic approach (HR 1.329; p = 0.010), and positive margins (HR 1.587; p < 0.001) were negatively associated with survival, while extent of resection (HR 1.189; p = 0.140) and lymphadenectomy (HR 1.039; p = 0.759) had no association. Stratified by stage, laparoscopic resection was only associated with worse survival in stage III disease (HR 1.548; p = 0.007). Chemoradiation was only associated with improved survival in patients with positive resection margins (HR 0.475; p = 0.004). CONCLUSION: Tumor biology and surgical margins are the primary determinants of survival in non-metastatic ACC. Surgical extent and lymphadenectomy are not associated with overall survival. In advanced disease, the open approach is associated with improved survival.

Development of a risk-prediction model for primary aldosteronism in veterans with hypertension.

BACKGROUND: Rates of screening for primary aldosteronism in patients who meet the criteria are exceedingly low (1%-3%). To help clinicians prioritize screening in patients most likely to benefit, we developed a risk-prediction model. METHODS: Using national Veterans Health Administration data, we identified patients who met the criteria for primary aldosteronism screening between 2000 and 2019. We performed multivariable logistic regression to identify characteristics associated with positive primary aldosteronism testing before generating a risk-scoring system based on the coefficients (0< ß < 0.5 = 1 pt, 0.5 ≤ ß < 1 = 2 pts, 1 ≤ ß < 1.5 = 3 pts) and then tested the system performance using an internal validation cohort. RESULTS: We identified 502,190 patients who met primary aldosteronism screening criteria, of whom 1.6% were screened and 15% tested positive. Based on the regression model, we generated a risk-scoring system based on a total of 9 possible points in which age under 50, absence of smoking history, and resistant hypertension each scored 1 point; elevated serum sodium 2 points; and hypokalemia 3 points. Rates of positive screening increased with risk score, with 5.6% to 6.7% of those scoring 0 points testing positive; 7.9% to 9.0% 1 point; 8.6% to 10% 2 points; 13% to 14% 3 points; 21% 4 points; 22% to 38% 5 points; 27% to 38% 6 points; 42% to 49% 7 points; and 50% to 51% ≥8 points. CONCLUSION: In hypertensive patients who meet the criteria for primary aldosteronism screening, rates of positive screening range from 5.6% to 51%. Use of our risk-predication model incorporating these factors can identify patients most likely to benefit from testing.

Disparities in Presentation, Treatment, and Survival in Anaplastic Thyroid Cancer.

BACKGROUND: Disparities have been previously described in the presentation, management, and outcomes of other thyroid cancer subtypes; however, it is unclear whether such disparities exist in anaplastic thyroid cancer (ATC). METHODS: We identified patients with ATC from the National Cancer Database (2004-2020). The primary outcomes were receipt of surgery, chemotherapy, and radiation. The secondary outcome was 1-year survival. Multivariable logistic and Cox proportional hazards regressions were used to assess the associations between sex, race/ethnicity, and the outcomes. RESULTS: Among 5359 patients included, 58% were female, and 80% were non-Hispanic white. Median tumor size was larger in males than females (6.5 vs. 6.0 cm; p < 0.001) and in patients with minority race/ethnicity than in white patients (6.5 vs. 6.0 cm; p < 0.001). After controlling for tumor size and metastatic disease, female patients were more likely to undergo surgical resection (odds ratio [OR]: 1.20; p = 0.016) but less likely to undergo chemotherapy (OR: 0.72; p < 0.001) and radiation (OR: 0.76; p < 0.001) compared with males. Additionally, patients from minority racial/ethnic backgrounds were less likely to undergo chemotherapy (OR: 0.69; p < 0.001) and radiation (OR: 0.71; p < 0.001) than white patients. Overall, unadjusted, 1-year survival was 23%, with differences in treatment receipt accounting for small but significant differences in survival between groups. CONCLUSIONS: There are disparities in the presentation and treatment of ATC by sex and race/ethnicity that likely reflect differences in access to care as well as patient and provider preferences. While survival is similarly poor across groups, the changing landscape of treatments for ATC warrants efforts to address the potential for exacerbation of disparities.

Multiple Complications in Emergency Surgery : Identifying Risk Factors for Failure-to-Rescue.

BACKGROUND: While the use of the failure-to-rescue (FTR) metric, or death after complication, has expanded beyond elective surgery to emergency general surgery (EGS), little is known about the trajectories patients take from index complication to death. METHODS: We conducted a retrospective cohort study of EGS operations using the National Surgical Quality Improvement Project (NSQIP) dataset, 2011-2017. 16 major complications were categorized as infectious, respiratory, thrombotic, cardiac, renal, neurologic, or technical. We tabulated common combinations of complications. We then use logistic regression analyses to test the hypotheses that (1) increase in the number and frequency of complications would yield higher FTR rates and (2) secondary complications that span a greater number of organ systems or mechanisms carry a greater associated FTR risk. RESULTS: Of 329 183 EGS patients, 69 832 (21.2%) experienced at least 1 complication. Of the 11 195 patients who died following complication (16.0%), 8205 (63.4%) suffered more than 1 complication. Multivariable regression analyses revealed an association between the number of complications and mortality risk (odds ratio [OR] 2.37 for 2 complications vs 1, P < .001). There was a similar increase in mortality with increased complication accrual rate (OR 3.29 for 0.2-0.4 complications/day vs <0.2, P < .001). Increasing the number of types of complication were similarly associated with mortality risk. DISCUSSION: While past FTR analyses have focused primarily on index complication, a broader consideration of ensuing trajectory may enable identification of high-risk cohorts. Efforts to reduce mortality in EGS should focus on attention to those who suffer a complication to prevent a cascade of downstream complications culminating in death.