Hypercalcemia and Postoperative Joint Symptoms Following Joint Replacement for Osteoarthritis.

INTRODUCTION: Calcium metabolism dysregulation in the setting of primary hyperparathyroidism (PHPT) mediated chondrocalcinosis is implicated in joint pain, a key element in the decision regarding arthroplasty for osteoarthritis. The relationship between hypercalcemia and joint pain, before and after arthroplasty, is unknown. This study investigates the association between preoperative hypercalcemia and postoperative outcomes following total knee (TKA) and total hip arthroplasty (THA). METHODS: A retrospective chart review was conducted on patients who underwent initial elective THA or TKA. Patients with a preoperative serum calcium >10.2 mg/dL were matched (1:2-1:4) with nearest neighbor to patients with normal serum calcium. THA and TKA functional outcomes were measured at baseline and 1-y postoperatively using patient-reported Hip Disability and Osteoarthritis Outcome Scores and Knee Injury and Osteoarthritis Outcome Scores surveys. Postoperative complications, readmissions, length of stay, and functional outcome scores were compared. RESULTS: Four hundred ninety-five patients (106 hypercalcemic cases, 389 matched controls) were included. Of these, 223 patients underwent THA (46 cases; 177 controls) and 272 patients underwent TKA (61 cases; 211 controls). There were no differences in Hip Disability and Osteoarthritis Outcome Scores and Knee Injury and Osteoarthritis Outcome Scores scores, postoperative complications, readmissions, or length of stay between cases and controls. Only 19/106 (18%) hypercalcemic patients had a parathyroid hormone (PTH); of these, 9 (47%) had possible PHPT (PTH > 40). CONCLUSIONS: Patients with hypercalcemia undergoing arthroplasty have similar functional and postoperative outcomes as normocalcemic patients. As PTH was obtained in <20% of hypercalcemic cases and 50% had possible PHPT, we recommend that hypercalcemic patients undergo PHPT workup. Additional investigation is needed to determine the effect of PHPT on arthroplasty outcomes.

Cosyntropin Stimulation Testing is More Selective than Postoperative Day 1 Basal Cortisol for Diagnosing Secondary Adrenal Insufficiency After Unilateral Adrenalectomy.

BACKGROUND: Secondary adrenal insufficiency (SAI) may occur in patients after unilateral adrenalectomy for adrenal-dependent hypercortisolism (HC) or primary aldosteronism (PA). This study aimed to assess whether postoperative day (POD) 1 basal cortisol was predictive of an abnormal cosyntropin stimulation test (CST) result and the need for glucocorticoid replacement (GR). METHODS: A retrospective review of consecutive patients who underwent unilateral adrenalectomy for HC, PA, or both between September 2014 and September 2022 was performed. On POD1, CST was performed for all the patients with HC, and before 2021 for all the patients with PA. The patients with an abnormal CST result were deemed at risk of SAI and discharged with GR. Receiver operating characteristic (ROC) curves were generated to evaluate the sensitivity (SN) and specificity (SP) of basal cortisol thresholds to predict an abnormal CST result. RESULTS: The patients underwent unilateral adrenalectomy for overt hypercortisolism (OH; n = 42), mild autonomous cortisol excess (MACE; n = 70), mixed PA/HC (n = 22), or PA (n = 73). On POD1, CST was performed for 152 patients (93% OH, 96% MACE,73% PA/HC, 41% PA), and 80 patients (53%) had SAI (67% OH, 55% MACE, 44% PA/HC, 33% PA). The SN and SP of a basal cortisol level of 10 µg/dL or lower to predict an abnormal CST were respectively 92% and 77% for OH, 94% and 73% for MACE, 100% and 85% for PA, and 100% and 67% for PA/HC. The optimal basal cortisol level for predicting an abnormal CST for patients with PA or PA/HC was 5 µg/dL or lower (SN/SP, 100%). CONCLUSIONS: After unilateral adrenalectomy for HC, PA, or mixed PA/HC, POD1 CST improved identification of patients at risk for SAI compared with basal cortisol levels alone. The authors recommend that POD1 CST be performed to determine the risk for SAI and the need for postoperative GR after unilateral adrenalectomy for patients with HC.

Surgical Management of Secondary and Tertiary Hyperparathyroidism.

Secondary hyperparathyroidism (SHPT) often arises from kidney disease and is characterized by elevated parathyroid hormone (PTH) levels. The reported optimal PTH level to balance the compensatory physiologic response in SHPT with the pathologic morbidity and mortality has changed over time with our evolving understanding. Parathyroidectomy for kidney-related hyperparathyroidism requires consideration of the patient's dialysis status, potential for kidney transplantation, and medical history. Extent of parathyroidectomy and intraoperative decision-making requires consideration to maximize cure with the risk of permanent hypoparathyroidism. Parathyroidectomy for kidney-related hyperparathyroidism can provide a reduction in morbidity, mortality, and improved kidney allograft function and survival.

Charting the Course: Insights into Neuroendocrine Tumor Dynamics in the United States.

OBJECTIVE: To explore changing trends and characteristics in neuroendocrine tumors (NETs) epidemiology, focusing on demographics, clinical aspects, and survival, including the impact of social determinants of health (SDOH) on outcomes. BACKGROUND: The escalating incidence and prevalence of NETs underscore the pressing need for updated epidemiologic data to reveal the evolving landscape of this condition. Access to current information is imperative for informing clinical strategies and public health initiatives targeting NETs. METHODS: A retrospective, population-based study analyzed NET patient data from 1975 to 2020, using the Surveillance, Epidemiology, and End Results (SEER 8, 12, 18) program. We calculated annual age-adjusted incidence, prevalence, and 5-year overall survival (OS) rates. Survival trends from 2000 to 2019 were examined, employing the Fine-Gray model to evaluate cancer-specific mortality. RESULTS: NETs' age-adjusted incidence rate quadrupled from 1.5 per 100,000 in 1975 to 6.0 per 100,000 in 2020. A decline in incidence occurred from 6.8 per 100,000 in 2019 to 6.0 per 100,000 in 2020. All-cause survival multivariable analysis demonstrated high grade (HR: 2.95, 95% CI: 2.63-3.09, P<0.001), single patients (HR: 1.49, 95% CI: 1.45-1.54, P<0.001), and Black patients (HR: 1.17, 95% CI:1.13-1.22, P<0.001) all had worse survival than their controls. CONCLUSION: In conclusion, our study shows a steady increase in NETs incidence until 2019, with a decline in 2020. Understanding the reasons behind this trend is vital for improved management and public health planning. Further research should focus on the factors driving these changes to enhance our understanding of NET epidemiology.

Medical Student Perceptions of Family Planning During Residency Training in Surgical Fields.

INTRODUCTION: Several studies have investigated surgical residents' perceptions of family planning, and many have investigated medical students' perceptions of surgical specialties; however, there is limited research on medical students' perceptions of the impact of family planning on the decision to pursue surgical training. This study aims to investigate male and female medical students' perceptions of family planning in residency. METHODS: A survey was distributed to all medical students at a single medical school in the Midwest between February 2023 and June 2023. The survey was adapted from a prior study investigating resident perceptions of family planning. It included questions about parental leave, having children, and perceived barriers to family planning. RESULTS: One hundred students completed surveys. Seventy-four (74%) respondents identified as female and 57 (57%) were interested in surgery. Approximately half (55, 55%) of the respondents were strongly or definitely considering having children during residency. However, only eight (8%) students were aware of policies applicable to having children during residency. A majority (85, 85%) felt the decision to pursue surgical residency would prevent or delay having children at their preferred time. Most students felt they would be negatively perceived by peers (62, 62%) and faculty (87, 87%) if they had children during training. The highest perceived barriers to having children during training were work-time demands, childcare barriers, and time away from training. CONCLUSIONS: Both men and women are interested in having children during residency but are unaware of the relevant parental leave policies and are concerned about how training will be impacted by taking time away or a lack of flexibility. Without transparency and flexibility in surgical residency, both men and women may forgo having children during training or choose a specialty they perceive to be more conducive to childbearing.

Making Choices: A Multi-institutional, Longitudinal Cohort Study Assessing Changes in Treatment Outcome Valuation for Low-Risk Thyroid Cancer.

OBJECTIVE: To evaluate the relative importance of treatment outcomes to patients with low-risk thyroid cancer (TC). SUMMARY BACKGROUND DATA: Overuse of total thyroidectomy (TT) for low-risk TC is common. Emotions from a cancer diagnosis may lead patients to choose TT resulting in outcomes that do not align with their preferences. METHODS: Adults with clinically low-risk TC enrolled in a prospective, multi-institutional, longitudinal cohort study from 11/2019-6/2021. Participants rated treatment outcomes at the time of their surgical decision and again 9 months later by allocating 100 points amongst 10 outcomes. T-tests and Hotelling's T 2 statistic compared outcome valuation within and between subjects based on chosen extent of surgery (TT vs. lobectomy). RESULTS: Of 177 eligible patients, 125 participated (70.6% response) and 114 completed the 9-month follow-up (91.2% retention). At the time of the treatment decision, patients choosing TT valued the risk of recurrence more than those choosing lobectomy and the need to take thyroid hormone less ( P <0.05). At repeat valuation, all patients assigned fewer points to cancer being removed and the impact of treatment on their voice, and more points to energy levels ( P <0.05). The importance of the risk of recurrence increased for those who chose lobectomy and decreased for those choosing TT ( P <0.05). CONCLUSION: The relative importance of treatment outcomes changes for patients with low-risk TC once the outcome has been experienced to favor quality of life over emotion-related outcomes. Surgeons can use this information to discuss the potential for asthenia or changes in energy levels associated with total thyroidectomy.

The Role of Demographic and Clinical Factors in Germline Mutation Testing for Patients with Primary Hyperparathyroidism.

INTRODUCTION: Guidelines recommending genetic counseling in primary hyperparathyroidism (PHPT) vary. To further delineate current recommendations, this study examined genetic counseling referral patterns and rates of mutations in surgical patients with PHPT. PATIENTS AND METHODS: A single-institution review was performed of adult patients who underwent parathyroidectomy for presumed sporadic PHPT. Genetic testing indications of hypercalcemia onset ≤ 40 years, multigland disease (MGD), family history (FHx) of PHPT, or other clinical indications suspicious for a PHPT-related endocrinopathy were examined by demographics and mutation detection rates. RESULTS: Genetic counseling was performed in 237 (37.9%) of 625 patients. Counseling was discussed but not performed in 121 (19.4%) patients. No evidence was noted of genetic referral discussion in the remaining 267 (42.7%). Of these groups, patients who received genetic counseling were youngest, p < 0.001 [median age 55.3 (IQR 43.2, 66.7) years]. The majority of patients with indications of age ≤ 40 years (65.7%), FHx (78.0%), and other clinical indications (70.7%) underwent genetic counseling, while most with MGD (57.0%) did not. Eight mutations were detected in 227 patients (3.5%). Mutations included: MEN1 (n = 2), CDC-73 (n = 4), and CASR (n = 2). Detection was most common in patients with FHx (4/71, 5.6%), then age ≤ 40 years (3/66, 4.5%), and other clinical indications (3/80, 3.8%). No mutations were identified in 48 patients tested solely for MGD. CONCLUSIONS: Most patients with onset of hypercalcemia age ≤ 40 years, positive FHx, or other clinical concerns underwent genetic counseling, while most with MGD did not. As no germline mutations were identified in patients with MGD alone, further investigation of MGD as a sole indication for genetic counseling may be warranted.

Selpercatinib combination with the mitochondria-targeted antioxidant MitoQ effectively suppresses RET-mutant thyroid cancer.

Genetic alternation of REarranged during Transfection (RET) that leads to constitutive RET activation is a crucial etiological factor for thyroid cancer. RET is known to regulate mitochondrial processes, although the underlying molecular mechanisms remain unclear. We previously showed that the multi-kinase inhibitors vandetanib and cabozantinib increase the mitochondrial membrane potential (Δψm) in RET-mutated thyroid tumor cells and that this effect can be exploited to increase mitochondrial enrichment of Δψm-sensitive agents in the tumor cells. In this study, we hypothesized that the RET-selective inhibitor, selpercatinib, can increase Δψm and, subsequently, tumor cell uptake of the mitochondria-targeted ubiquinone (MitoQ) to the level to break the mitochondrial homeostasis and induce lethal responses in RET-mutated thyroid tumor cells. We show that selpercatinib significantly increased Δψm, and its combination with MitoQ synergistically suppressed RET-mutated human thyroid tumor cells, which we validated using RET-targeted genetic approaches. Selpercatinib and MitoQ, in combination, also suppressed CCDC6-RET fusion cell line xenografts in mice and prolonged animal survival more effectively than single treatments of each agent. Moreover, we treated two patients with CCDC6-RET or RETM918T thyroid cancer, who could not take selpercatinib at regular doses due to adverse effects, with a dose-reduced selpercatinib and MitoQ combination. In response to this combination therapy, both patients showed tumor reduction. The quality of life of one patient significantly improved over a year until the tumor relapsed. This combination of selpercatinib with MitoQ may have therapeutic potential for patients with RET-mutated tumors and intolerant to regular selpercatinib doses.

Racial and Ethnic Disparities in the Diagnosis and Treatment of Thyroid Disease.

CONTEXT: There are differences in diagnosis, treatment, and outcomes for thyroid between racial and ethnic groups that contribute to disparities. Identifying these differences and their causes are the key to understanding and reducing disparities in presentation and outcomes in endocrine disorders. EVIDENCE ACQUISITION: The present study reviews original studies identifying and exploring differences between benign and malignant thyroid diseases. A PubMed, Web of Science, and Scopus search was conducted for English-language studies using the terms "thyroid," "thyroid disease," "thyroid cancer," "race," "ethnicity," and "disparities" from inception to December 31, 2022. EVIDENCE SYNTHESIS: Many racial and ethnic disparities in the diagnosis, presentation, treatment, and outcomes of thyroid disease were found. Non-White patients are more likely to have a later time to referral, to present with more advanced disease, to have more aggressive forms of thyroid cancer, and are less likely to receive the appropriate treatment than White patients. Overall and disease-specific survival rates are lower in Black and Hispanic populations when compared to White patients. CONCLUSIONS: Extensive disparities exist in thyroid disease diagnosis, treatment, and outcomes that may have been overlooked. Further work is needed to identify the causes of these disparities to begin to work toward equity in the care of thyroid disease.

Ablation techniques or active surveillance compared to surgical resection in patients with low-risk papillary thyroid cancer: a systematic review and meta-analysis.

BACKGROUND: The global prevalence of thyroid cancer is on the rise. About one-third of newly diagnosed thyroid cancer cases comprise low-risk papillary thyroid cancer (1.5 cm or more minor). While surgical removal remains the prevailing approach for managing low-risk papillary thyroid cancer (LPTC) in patients, other options such as active surveillance (AS), radiofrequency ablation (RFA), microwave ablation (MWA), and laser ablation (LA) are also being considered as viable alternatives. This study evaluated and compared surgical thyroid resection (TSR) versus non-surgical (NS) methods for treating patients with LPTC. METHODS: The study encompassed an analysis of comparisons between surgical thyroid resection (TSR) and alternative approaches, including active surveillance (AS), radiofrequency ablation (RFA), microwave ablation (MWA), or laser ablation (LA). The focus was on patients with biopsy-confirmed low-risk papillary thyroid cancer (LPTC) of less than 1.5 cm without preoperative indications of local or distant metastasis. The primary outcomes assessed were recurrence rates, disease-specific mortality, and quality of life (QoL). Data were collected from prominent databases, including Cochrane Database, Embase, MEDLINE, and Scopus, from inception to June 3rd, 2020. The CLARITY tool was utilized to evaluate bias risk. The analysis involved odds ratios (OR) with 95% confidence intervals (CI) for dichotomous outcomes, as well as mean differences (MD) and standardized mean differences (SMD) for continuous outcomes. The study is registered on PROSPERO under the identifier CRD42021235657. RESULTS: The study incorporated 13 retrospective cohort studies involving 4034 patients. Surgical thyroid resection (TSR), active surveillance (AS), and minimally invasive techniques like radiofrequency ablation (RFA), microwave ablation (MWA), and laser ablation (LA) were performed in varying proportions of cases. The analysis indicated that specific disease mortality rates were comparable among AS, MWA, and TSR groups. The risk of recurrence, evaluated over different follow-up periods, showed no significant differences when comparing AS, RFA, MWA, or LA against TSR. Patients undergoing AS demonstrated better physical health-related quality of life (QoL) than those undergoing TSR. However, no substantial differences were observed in the overall mental health domain of QoL when comparing AS or RFA with TSR. The risk of bias was moderate in nine studies and high in four. CONCLUSION: Low-quality evidence indicates comparable recurrence and disease-specific mortality risks among patients with LPTC who underwent ablation techniques or active surveillance (AS) compared to surgery. Nevertheless, individuals who opted for AS exhibited enhanced physical quality of life (QoL). Subsequent investigations are warranted to validate these findings.

Older Patients With Asymptomatic Primary Hyperparathyroidism: Should Criteria for Surgery Be Expanded?

Context: Patients with primary hyperparathyroidism (PHPT) can present with variable signs, symptoms, and end-organ effects. Clinical practice guidelines influence referral for consideration of parathyroidectomy. Objective: This study compared the demographic, biochemical, and symptom profile and examine indications for surgery in patients older than 50 years who underwent parathyroidectomy to determine how changes to current guidelines may affect recommendations for parathyroidectomy. Methods: A retrospective review was conducted of patients age 50 years or older who underwent initial parathyroidectomy for sporadic PHPT from 2012 to 2020. Patients were classified by indications for surgery per guideline criteria (classic, asymptomatic, and no criteria met) and age group (AG): 50 to 59 years; 60 to 69 years; 70 years or older. Patients were treated at a high-volume tertiary medical center by endocrine surgeons. Results: Of 1182 patients, 367 (31%) classic and 660 (56%) asymptomatic patients met the criteria for surgery. The most common indications for surgery were extent of hypercalcemia (51%), osteoporosis (28%), and nephrolithiasis (27%). Of the 155 (13%) patients who did not meet the criteria, neurocognitive symptoms (AG1: 88% vs AG2: 81% vs AG3: 70%; P = .14) and osteopenia (AG1: 53% vs AG2: 68% vs AG3: 68%; P = .43) were frequently observed regardless of patient age. If the age threshold of younger than 50 years was expanded to 60, 65, or 70 years, an additional 61 (5%), 99 (8%), and 124 (10%) patients in the entire cohort would have met the guideline criteria for surgery, respectively. Conclusion: Expanding current guidelines for PHPT to include a broader age range, osteopenia, and neurocognitive symptoms may allow for earlier surgical referral and evaluation for definitive treatment.

Gender Disparities in General Surgery Resident Subspecialization.

BACKGROUND: There are an increasing number of women entering medical school and general surgery residency. Despite this, there remains an underrepresentation of women in some surgical specialties. The purpose of this study is to examine gender differences in fellowship subspecialization of recent general surgery graduates. METHODS: Graduating residents from general surgery residencies from 2016 to 2020 were identified. Referring to each residency's graduating resident website, we noted whether or not listed alumni were reported to have entered a fellowship. If applicants were listed as having completed a fellowship, the fellowship was noted along with each applicant's expressed gender. Differences across groups were analyzed using SPSS. RESULTS: The majority (82.4%) of graduates pursued a fellowship after residency training. Men were more likely to enter fellowships in Cardiothoracic Surgery, Plastic and Reconstructive Surgery, Vascular Surgery, and practice than women. Women were more likely to enter fellowships in Breast Surgery, Acute Care Surgery/Trauma Surgery, Pediatric Surgery, and Endocrine Surgery than men. CONCLUSIONS: The majority of general surgery residency graduates pursue fellowship training. Gender disparities continue for a minority of subspecialties for both men and women.

Patterns of Unnecessary Insurer Prior Authorization Denials in a Complex Surgical Oncology Practice.

INTRODUCTION: Insurance prior authorization (PA) is a determination of need, required by a health insurer for an ordered test/procedure. If the test/procedure is denied, a peer-to-peer (P2P) discussion between ordering provider and payer is used to appeal the decision. The objective of this study was to measure the number and patterns of unnecessary PA denials. METHODS: This was a retrospective review at a quaternary cancer center from October 2021 to March 2022. Included were all patients with outpatient imaging orders for surgical planning or surveillance of gastrointestinal, endocrine, or skin cancer. Primary outcome was unnecessary initial denial (UID) defined as an order that required preauthorization, was initially denied by the insurer, and subsequently overturned by P2P. RESULTS: Nine hundred fifty seven orders were placed and 419 required PA (44%). Of tests requiring authorization, 55/419 (13.1%) were denied. Variability in the likelihood of initial denial was seen across insurers, ranging from 0% to 57%. Following P2P, 32/55 were overturned (58.2% UID). The insurers most likely to have a UID were Aetna (100%), Anthem (77.8%), and Cigna (50.0%). UID was most common for gastrointestinal (58.9%) and endocrine (58.3%) cancers. Average P2P was 33.5 min (interquartile range 28-40). CONCLUSIONS: The majority of imaging studies initially denied were overturned after P2P. If all UIDs were eliminated, this would represent 108 less P2P discussions with an estimated time-savings of 60.3 h annually within a high-volume surgical oncology practice. Combined personnel costs to the health systems and stress on patients with cancer due to image-associated PAs and P2P appear hard to justify.

Adoption of Robotic Adrenalectomy: A Two-Institution Study of Surgeon Learning Curve.

BACKGROUND: Robotic adrenalectomy is feasible and safe, yet concerns over increased operative times and the learning curve (LC) for proficiency have limited its adoption. This study aimed to assess the LC for robotic adrenalectomy. METHODS: This is a two-institution retrospective review of consecutive unilateral minimally invasive adrenalectomies performed by four high-volume adrenal surgeons between 2007 and 2022. Two surgeons transitioned from laparoscopic to robotic adrenalectomy, and two surgeons adopted the approach, with proctoring, after completion of fellowship training without robotic experience. Operative time and complications were analyzed. Multivariable regression was used to identify factors associated with operative time. The number of cases required to overcome the LC was determined using the LC-cumulative-sum (LC-CUSUM) analysis. RESULTS: Of 457 adrenalectomies, 182 (40%) were laparoscopic and 275 (60%) robotic. The robotic approach was associated with shorter median operative time (106 vs 119 min; p = 0.002), fewer complications (6% vs 13%; p = 0.018), and fewer conversions to open adrenalectomy (1% vs 4%; p = 0.030), with no difference between the senior and junior surgeons. On adjusted analysis, factors associated with increased operative time were male sex (p < 0.001), BMI > 30 kg/m2 (p < 0.001), and higher gland weight (p < 0.001). The LC-CUSUM analysis showed proficiency after 8-29 procedures. Compared with the first 10 cases, there was a mean reduction in operative time of 14 min after 10-20 cases, 28 min after 20-30 cases, and 29 min after > 30 cases, regardless of surgeon experience. DISCUSSION: With dedicated teams and proctoring, robotic adrenalectomy can be safely adopted at high-volume centers with a minimal LC.