Deciphering cellular plasticity in pancreatic cancer for effective treatments.

Cellular plasticity and therapy resistance are critical features of pancreatic cancer, a highly aggressive and fatal disease. The pancreas, a vital organ that produces digestive enzymes and hormones, is often affected by two main types of cancer: the pre-dominant ductal adenocarcinoma and the less common neuroendocrine tumors. These cancers are difficult to treat due to their complex biology characterized by cellular plasticity leading to therapy resistance. Cellular plasticity refers to the capability of cancer cells to change and adapt to different microenvironments within the body which includes acinar-ductal metaplasia, epithelial to mesenchymal/epigenetic/metabolic plasticity, as well as stemness. This plasticity allows heterogeneity of cancer cells, metastasis, and evasion of host's immune system and develops resistance to radiation, chemotherapy, and targeted therapy. To overcome this resistance, extensive research is ongoing exploring the intrinsic and extrinsic factors through cellular reprogramming, chemosensitization, targeting metabolic, key survival pathways, etc. In this review, we discussed the mechanisms of cellular plasticity involving cellular adaptation and tumor microenvironment and provided a comprehensive understanding of its role in therapy resistance and ways to overcome it.

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.

Treatment of Hypercalcemic Hyperparathyroidism After Kidney Transplantation Is Associated With Improved Allograft Survival.

BACKGROUND: Hyperparathyroidism (HPT) and malignancy are the most common causes of hypercalcemia. Among kidney transplant (KT) recipients, hypercalcemia is mostly caused by tertiary HPT. Persistent tertiary HPT after KT is associated with allograft failure. Previous studies on managing tHPT were subjected to survivor treatment selection bias; as such, the impact of tertiary HPT treatment on allograft function remained unclear. We aim to assess the association between hypercalcemic tertiary HPT treatment and kidney allograft survival. MATERIALS AND METHODS: We identified 280 KT recipients (2015-2019) with elevated post-KT adjusted serum calcium and parathyroid hormone (PTH). KT recipients were characterized by treatment: cinacalcet, parathyroidectomy, or no treatment. Time-varying Cox regression with delayed entry at the time of first elevated post-KT calcium was conducted, and death-censored and all-cause allograft failure were compared by treatment groups. RESULTS: Of the 280 recipients with tHPT, 49 underwent PTx, and 98 received cinacalcet. The median time from KT to first elevated calcium was 1 month (IQR: 0-4). The median time from first elevated calcium to receiving cinacalcet and parathyroidectomy was 0(IQR: 0-3) and 13(IQR: 8-23) months, respectively. KT recipients with no treatment had shorter dialysis vintage (P = .017) and lower PTH at KT (P = .002), later onset of hypercalcemia post-KT (P < .001). Treatment with PTx (adjusted hazard ratio (aHR) = 0.18, 95%CI 0.04-0.76, P = .02) or cinacalcet (aHR = 0.14, 95%CI 0.004-0.47, P = .002) was associated with lower risk of death-censored allograft failure. Moreover, receipt of PTx (aHR = 0.28, 95%CI 0.12-0.66, P < .001) or cinacalcet (aHR = 0.38, 95%CI 0.22-0.66, P < .001) was associated with lower risk of all-cause allograft failure. CONCLUSIONS: This study demonstrates that treatment of hypercalcemic tertiary HPT post-KT is associated with improved allograft survival. Although these findings are not specific to hypercalcemia of malignancy, they do demonstrate the negative impact of hypercalcemic tertiary HPT on kidney function. Hypercalcemic HPT should be screened and aggressively treated post-KT.

The Rich Get Richer: The Matthew Effect in Open Payments.

INTRODUCTION: The Matthew Effect refers to a pattern of accumulated advantage, specifically how social status can lead to increased wealth and recognition. The Physician Payments Sunshine Act of the Affordable Care Act requires industry payments and the affiliated hospital to be publicly available through the Open Payments Database (OPD). The US News and World Report (USNWR) publishes a ranking of best medical school (research) programs yearly. The Blue Ridge Institute for Medical Research (BRIMR) ranks medical schools annually by the amount of funding from the National Institutes of Health (NIH). Whether medical school-affiliated hospitals with higher social ranking and more NIH funding receive more industrial support is unknown. This study aims to evaluate the relationship between open payment of medical school-affiliated hospitals and USNWR and BRIMR ranking. METHODS: We performed a cross-sectional analysis of the OPD for the fiscal year of 2021. Hospital industry payment information was collected for affiliated hospitals in general and research categories. NIH funding data and program rankings were collected from BRIMR and USNWR, respectively. All data were collected for the fiscal year of 2021. The open payments of schools ranked in the top 50 for USNWR (n = 50) and BRIMR (n = 49) were compared to the schools not ranked in the top 50 using SPSS with chi-squared and Mann-Whitney U tests. A multivariate linear regression was performed to evaluate the association between open payments, USNWR ranking, and BRIMR ranking. RESULTS: A total of 91 medical schools were included in this study. The top 50 ranked medical schools by BRIMR were found to have a higher median of total open payment ($5,652,628 versus $2,558,372, P < 0.001), open payment in research ($4,707,297 versus $1,992,597, P = 0.003), and general open payment ($1,083,018 versus $392,045, P < 0.001). When ranked by USNWR, the top 50 ranked medical schools were found similarly to have a higher median of total open payment (P < 0.001), open payment in research (P < 0.001), and general open payment (P < 0.001). USNWR ranking was an independent predictor of more total open payment (Coefficient 0.016, 95% confidence interval 0.002-0.029, P = 0.026) and research open payment (coefficient 0.018, 95% confidence interval 0.002-0.034, P = 0.028). USNWR ranking was not found to predict general open payments. BRIMR ranking was not associated with open payment in total, research, or general. CONCLUSIONS: Hospital open payments were associated with the social reputation of their medical schools. NIH funding was not associated with open payments. A Matthew effect exists in current industry payments to medical school-affiliated hospitals.

An Evaluation of Health Literacy in Patients Undergoing Surgical Evaluation for Thyroid Disease.

INTRODUCTION: Health literacy (HL) is the ability to comprehend and apply health information to make informed health-care decisions. Poor HL results in the inability to provide informed consent, medication noncompliance, inconsistent follow-up, and delayed seeking of care. Data about HL in endocrine surgery is currently lacking. In this study, we aimed to evaluate the HL of patients with thyroid disease and identify risk factors for limited HL. METHODS: We evaluated a total of 172 patients with thyroid disease in a single endocrine surgery clinic. HL was determined by the Brief Health Literacy Screening Tool, a validated HL screening questionnaire in which patient scores correlate to limited, marginal, or adequate HL. Demographic data including age, sex, race, diagnosis, employment status, and median annual income were obtained. Analysis of variance, t-test, and Chi-square test were used to compare HL between and within each demographic domain. P < 0.05 was considered significant. RESULTS: Of the 172 patients, 77% had adequate HL, 16% had marginal HL, and 7% had limited HL. Patients with higher education exhibited greater HL (P < 0.001). Ninety-three percent of patients with college/postgraduate degree had adequate HL, while of those with some college only 79% had adequate HL and of those with high school or less only 48.6% had adequate HL. There was minimal variation among age, sex, race, diagnosis, employment status, or income. CONCLUSIONS: Most patients with thyroid diseases from the endocrine surgery clinic at our institution have adequate HL. Limited education is a risk factor for low HL.

Feasibility of an Online Patient-Driven International Parathyroid Registry.

INTRODUCTION: Traditional parathyroid registries are labor-intensive and do not always capture long-term follow-up data. This study aimed to develop a patient-driven international parathyroid registry and leverage community connections to improve patient-centered care for hyperparathyroidism. METHODS: An anonymous voluntary online survey was developed using Qualtrics and posted in an international patient and advocate-run social media group affiliated with over 11,700 members. The survey was developed from a literature review, expert opinion, and discussion with the social media group managers. It consists of seven sections: patient demographics, past medical history, preoperative symptoms, laboratory evaluation, preoperative imaging studies, operative findings, and operative outcomes. RESULTS: From July 30, 2022, to October 1, 2022, 89 complete responses were received. Participants were from 12 countries, mostly (82.0%) from the United States across 31 states. Most participants were female (91.4%), White (96.7%) with a mean (±standard deviation) age of 58 ± 12 y. The most common preoperative symptoms were bone or joint pain (84.3%) and neuropsychiatric symptoms: including fatigue (82.0%), brain fog (79.8%), memory loss (79.8%), and difficulty with concentration (75.3%). The median (interquartile range) length from symptom onset to diagnosis was 40.0 (6.8-100.5) mo. Seventy-one percent of participants had elevated preoperative serum calcium, and 73.2% had elevated preoperative parathyroid hormone. All participants obtained preoperative imaging studies (88.4% ultrasound, 86.0% sestabimi scan, and 45.3% computed tomography). Among them, 48.8% of participants received two, and 34.9% had three imaging studies. The median (interquartile range) time from diagnosis to surgical intervention was 3 (2-9) mo. Twenty-two percent of participants traveled to different cities for surgical intervention. Forty-seven percent of participants underwent outpatient parathyroidectomy. Eighty-four percent of participants reported improved symptoms after parathyroidectomy, 12.4% required oral calcium supplementation for more than 6 mo, 32.6% experienced transient hoarseness after parathyroidectomy, and 14.6% required reoperation after initial parathyroidectomy. CONCLUSIONS: This international online parathyroid registry provides a valuable collection of patient-entered clinical outcomes. The high number of responses over 10 wk demonstrates that participants were willing to be involved in research on their disease. The creation of this registry allows global participation and is feasible for future studies in hyperparathyroidism.

LinkedIn Usage Trends Among Surgeons at a Large Academic Institute.

INTRODUCTION: Social networking platforms have evolved into a self-promotional space. The LinkedIn platform allows users to share knowledge, research accomplishments, and network in an academic setting. Our objective was to determine LinkedIn usage trends among surgeons at a large academic institution. METHODS: A list of surgeons within the department of surgery at a large academic institute was compiled. All publicly available profiles were analyzed for their LinkedIn activity and followership. Active accounts were defined as users who have posted or interacted with any posts within the last year. Comparisons of LinkedIn usage grouped by gender, surgery division, and rank were analyzed. RESULTS: A total of 133 surgeons were included. Among these surgeons, 88 had a LinkedIn profile (66.2%); however, only 43 surgeons had active usage on this platform (32.3%). The median number of followers among surgeons with a profile was 110 (IQR [24-427]). Male surgeons had a higher median of followers (167 IQR [38-502]) compared to female (54 IQR [21-209]). A greater percentage of male surgeons had a profile compared to female surgeons (68.5% M versus 61.0% F, P = 0.12). The transplant surgery division had the highest percentage of LinkedIn accounts (90.9%) followed by surgical oncology (87.5%). However, active usage was led by the pediatric surgery division (80.0%), followed by the plastic surgery division (71.4%). Instructors, assistant professors, associate professors, and professors all had LinkedIn accounts; however, instructors were the least active users with 33.3% being active on their LinkedIn. The lowest percentage of those with LinkedIn accounts were instructors (50%). Professors were found to be the most active users at 57.1%. CONCLUSIONS: Social media use is on the rise in academic surgery. Within a department of surgery at a large academic institution, only 32.3% were active users of LinkedIn, suggesting that there is room for improvement in utilizing this resource as a tool for mentorship, professional development, and networking.

Observations on the Representation of Asians in Surgical Training and Leadership.

INTRODUCTION: Diversity in medicine has a positive effect on outcomes, especially for Asian patients. We sought to evaluate representation of Asians across entry and leadership levels in surgical training. METHODS: Publicly accessible population data from 2018 to 2023 were collected from the US Census Bureau, the Association of American Medical Colleges, and the American Board of Surgery (ABS). Frequencies based on self-identified Asian status were identified, and proportions were calculated. RESULTS: The US census showed Asians constituted 4.9% of the US population in 2018 versus 6% in 2023. The proportion of Asian medical students rose from 21.6% to 24.8%; however, Asian surgical residency applicants remained constant at 20%. ABS certifications of Asians have increased from 13.7% to 18.5%. ABS examiners increased from 15.7% to 17.1%. CONCLUSIONS: In 5 years, Asians have made numeric gains in medical school and surgical training. However, Asian representation lags at Board examiner levels compared to the medical student population. The ABS has made recent efforts at transparency around examiner and examinee characteristics. A pillar of ensuring a well-trained surgical workforce to serve the public is to mandate that all surgical trainees and graduates undergo fair examinations, and are fairly assessed on their qualifications. Observed progress should further invigorate all surgical applicants, residents and leadership to take an even more active role in making surgery more diverse and welcoming to all, by including careful analyses of diversity at all levels.

Evaluating Patients' Health Literacy to Improve Thyroid Pathology Reports.

INTRODUCTION: As our growing population demonstrates a significant increase in the incidence of thyroid cancer, so does patient access to their medical records. Poor health literacy and understanding of disease severity, underscores the importance of effective and accessible patient-doctor communication. No previous studies on patient understanding of thyroid pathology reports exist; therefore, we sought to characterize health literacy in this population. METHODS: Using a modified Delphi technique, a 12-question multiple-choice survey regarding common pathology terms with possible definitions for each term was synthesized and administered to patients in a high-volume endocrine surgery clinic. Survey results, patient demographics, history of prior thyroid procedure (biopsy or surgery), and self-reported health literacy were collected. Data analysis included t tests, chi-squared, and multivariable linear regression using R. RESULTS: The survey was completed by 54 patients (response rate: 69.8%). On univariate analysis, White race, previous thyroid procedure, and at least a high school level education were all more likely to score higher on the survey than their counterparts (P < 0.05). On multivariable logistic regression for predicting a higher survey score, only race (est: 2.48 [95% confidence interval: 1.01-3.96]) and higher educational attainment (est: 3.98 [95% confidence interval: 2.32-5.64]) remained predictive (P < 0.05). The remaining demographic groups (age, health literacy confidence, and previous thyroid procedure) did not show a statistically significant difference. CONCLUSIONS: Overall, terms on a thyroid pathology report are poorly understood by patients. This is exacerbated by non-White race and low educational attainment. There is a need for patient-facing pathology education.

Does Graves' Disease Truly Increase the Risk of Complications After Total Thyroidectomy?

INTRODUCTION: Total thyroidectomy (TTx) has been reported to be more challenging in patients with Graves' disease, especially in those who are hyperthyroid at the time of surgery. Our aim was to compare outcomes in patients undergoing TTx for Graves' disease compared to other thyroid diseases at a large academic institution with high-volume fellowship-trained endocrine surgeons. METHODS: In our retrospective analysis from December 2015 to May 2023, patients undergoing TTx for Graves' disease were compared to those undergoing TTx for all other indications excluding advanced malignancy (poorly differentiated thyroid cancer and concomitant neck dissections). Patient demographics, biochemical values, and postoperative outcomes were compared. A subgroup analysis was performed comparing hyperthyroid to euthyroid patients at the time of surgery. RESULTS: There were 589 patients who underwent TTx, of which 227 (38.5%) had Graves' disease compared to 362 (61.5%) without. Intraoperatively in Graves' patients, nerve monitoring was used more frequently (65.6% versus 57.1%; P = 0.04) and there was a higher rate of parathyroid autotransplantation (32.0% versus 14.4%; P < 0.01). Postoperatively, transient voice hoarseness occurred less frequently (4.8% versus 13.6%; P < 0.01) and there was no difference in temporary hypocalcemia rates or hematoma rates. In our subgroup analysis, 83 (36%) of Graves' patients were hyperthyroid (thyroid-stimulating hormone < 0.45 and free T4 > 1.64) at the time of surgery and there were no differences in postoperative complications compared to those who were euthyroid. CONCLUSIONS: At a high-volume endocrine surgery center, TTx for Graves' disease can be performed safely without significant differences in postoperative outcomes. Hyperthyroid patients demonstrated no differences in postoperative outcomes.

Young and resilient: Unraveling papillary thyroid cancer outcomes in males under 40.

BACKGROUND: While males present with more adverse clinicopathologic features in papillary thyroid carcinoma (PTC), younger age has previously been shown to be a favorable prognostic factor. We examined the combined effect of male sex and young age on PTC outcomes. METHODS: We conducted a retrospective analysis of a prospectively maintained database of thyroid cancer surgery patients (2000-2020) at a single quaternary care institution. We included papillary thyroid carcinoma cases and excluded those with prior cancer-related thyroid surgery. We examined demographics, cancer stage, surgical outcomes, and complications by age and sex, analyzing groups below and above the age of 40 years. RESULTS: A total of 680 patients with PTC were included. Females constituted 68% (age ≥40 years: 44% and <40 years: 24%) and males 32% (≥40 years: 24% and <40 years: 8%). A significant difference (p < 0.001) of N1 disease distribution was found between the groups. N1a metastasis was greater in patients younger than 40 regardless of sex ((M < 40 (15%), F < 40 (15%), M ≥ 40 (12%), and F ≥ 40 (9%)). While, M < 40 had greater N1b metastasis (36%) than all other groups (M ≥ 40 (28%), F < 40 (22%), and F ≥ 40 (10%)). There was no significant difference in the distribution of T stages between groups. Groups showed no differences in 30-day outcomes, recurrence at 1 year, reoperation, mortality, nerve injury, or hypocalcemia. CONCLUSIONS: Young males with PTC face increased occurrence of nodal metastasis yet experience similar recurrence rates as their female and older counterparts. Subgroup analysis underscores the predictive role of sex and age in advanced PTC cases.

The Effects of Parathyroidectomy vs Medical Treatments for Secondary Hyperparathyroidism in Patients Undergoing Dialysis: A Meta-Analysis.

OBJECTIVE: The management of secondary hyperparathyroidism in patients undergoing dialysis is debated, with uncontrolled parathyroid hormone (PTH) levels becoming more common despite the expanded use of medical treatments like cinacalcet. This study examines the clinical benefits of parathyroidectomy vs medical treatment in reducing mortality and managing key laboratory parameters in patients undergoing dialysis. METHODS: PubMed, Embase, Cochrane, Scopus, and Web of Science databases were searched for cohort studies or randomized controlled trials published before August 18, 2023. We included studies with comparative arms, specifically medical treatment vs surgical intervention. Patients with a history of kidney transplant were excluded. Outcomes were analyzed using hazard ratios (HRs) for mortality and weighted mean differences (WMD) for laboratory parameters. RESULTS: Twenty-three studies involving 24 398 patients were analyzed. The pooled meta-analysis has shown a significant reduction in all-cause (HR, 0.47; 95% confidence interval [CI], 0.35-0.61) and cardiovascular mortality (HR, 0.58; 95% CI, 0.40-0.84) for parathyroidectomy vs medical treatments. Subgroup analysis showed that parathyroidectomy was associated with a greater reduction in mortality in patients with a PTH level over 585 pg/mL (HR, 0.37; 95% CI, 0.24-0.58). No mortality difference was found when all patients in the medical group received cinacalcet alongside standard medical treatment (HR, 1.02; 95% CI, 0.49-2.11). Parathyroidectomy also led to a larger decrease in PTH (WMD, 1078 pg/mL; 95% CI, 587-1569), calcium (WMD, 0.86 mg/dL; 95% CI, 0.43-1.28), and phosphate (WMD, 0.74 mg/dL; 95% CI, 0.32-1.16). CONCLUSION: Parathyroidectomy may offer a survival advantage compared to medical management in patients with severe secondary hyperparathyroidism.

Aberrant transcription factors in the cancers of the pancreas.

Transcription factors (TFs) are essential for proper activation of gene during the process of organogenesis, differentiation, lineage specificity. Reactivation or dysregulation of TFs regulatory networks could lead to deformation of organs, diseases including various malignancies. Currently, understanding the mechanism of oncogenesis became a necessity for the development of targeted therapeutic strategy for different cancer types. It is evident that many TFs go awry in cancers of the pancreas such as pancreatic ductal adenocarcinoma (PDAC) and pancreatic neuroendocrine neoplasms (PanNENs). These mutated or dysregulated TFs abnormally controls various signaling pathways in PDAC and PanNENs including RTK, PI3K-PTEN-AKT-mTOR, JNK, TGF-ß/SMAD, WNT/ß-catenin, SHH, NOTCH and VEGF which in turn regulate different hallmarks of cancer. Aberrant regulation of such pathways have been linked to the initiation, progression, metastasis, and resistance in pancreatic cancer. As of today, a number of TFs has been identified as crucial regulators of pancreatic cancer and a handful of them shown to have potential as therapeutic targets in pre-clinical and clinical settings. In this review, we have summarized the current knowledge on the role and therapeutic usefulness of TFs in PDAC and PanNENs.

Resolution of Secondary Hyperparathyroidism After Kidney Transplantation and the Effect on Graft Survival.

OBJECTIVE: Hyperparathyroidism (HPT) is nearly universal in patients with end-stage kidney disease. Kidney transplantation (KT) reverses HPT in many patients, but most studies have only focused on following calcium and not parathyroid hormone (PTH) levels. We sought to study the prevalence of persistent HPT post-KT at our center and its effect on graft survival. METHODS: Patients who underwent KT from January 2015 to August 2021 were included and characterized by post-KT HPT status at the most recent follow-up: resolved (achieving normal PTH post-KT) versus persistent HPT. Those with persistent HPT were further stratified by the occurrence of hypercalcemia (normocalcemic versus hypercalcemic HPT). Patient demographics, donor kidney quality, PTH and calcium levels, and allograft function were compared between groups. Multivariable logistic regression and Cox regression with propensity score matching were conducted. RESULTS: Of 1554 patients, only 390 (25.1%) patients had resolution of renal HPT post-KT with a mean (±SD) follow-up length of 40±23 months. The median (IQR) length of HPT resolution was 5 (0-16) months. Of the remaining 1164 patients with persistent HPT post-KT, 806 (69.2%) patients had high PTH and normal calcium levels, while 358 (30.8%) patients had high calcium and high PTH levels. Patients with persistent HPT had higher parathyroid hormone (PTH) at the time of KT [403 (243-659) versus 277 (163-454) pg/mL, P <0.001] and were more likely to have received cinacalcet treatment before KT (34.9% vs. 12.3%, P <0.001). Only 6.3% of patients with persistent HPT received parathyroidectomy. Multivariable logistic regression showed race, cinacalcet use pre-KT, dialysis before KT, receiving an organ from a deceased donor, high PTH, and calcium levels at KT were associated with persistent HPT post-KT. After adjusting for patient demographics and donor kidney quality by propensity score matching, persistent HPT (HR 2.5, 95% CI 1.1-5.7, P =0.033) was associated with a higher risk of allograft failure. Sub-analysis showed that both hypercalcemic HPT (HR 2.6, 95% CI 1.1-6.5, P =0.045) and normocalcemic HPT (HR 2.5, 95% CI 1.3-5.5, P =0.021) were associated with increased risk of allograft failure when compared with patients with resolved HPT. CONCLUSION: Persistent HPT is common (75%) after KT and is associated with a higher risk of allograft failure. PTH levels should be closely monitored after kidney transplantation so that patients with persistent HPT can be treated appropriately.

Somatostatin Receptor Type 2 and Thyroid-Stimulating Hormone Receptor Expression in Oncocytic Thyroid Neoplasms: Implications for Prognosis and Treatment.

Somatostatin receptor type 2 (SSTR2) and thyroid-stimulating hormone receptor (TSHR) display variable expression in primary thyroid tumors and have been implicated as theranostic targets. This study was designed to explore the differential expression of SSTR2 and TSHR in oncocytic (Hurthle cell) carcinoma (OC) vs oncocytic adenoma (OA). We performed a retrospective review for oncocytic neoplasms treated at our institution from 2012 to 2019. Formalin-fixed paraffin-embedded tissue blocks were used for tissue microarray construction. Tissue microarray blocks were cut into 5-µm sections and stained with anti-SSTR2 and anti-TSHR antibodies. Immunostains were analyzed by 3 independent pathologists. χ2 and logistic regression analysis were used to analyze clinical and pathologic variables. Sixty-seven specimens were analyzed with 15 OA and 52 OC. The mean age was 57 years, 61.2% were women, and 70% were White. SSTR2 positivity was noted in 2 OA (13%) and 15 OC (28%; 10 primary, 4 recurrent, and 1 metastatic) (P = .22). TSHR positivity was noted in 11 OA (73%) and 32 OC (62%; 31 primary and 1 metastatic) (P = .40). Those who presented with or developed clinical recurrence/metastasis were more likely to be SSTR2-positive (50% vs 21%; P = .04) and TSHR-negative (64.3% vs 28.9%; P = .02) than primary OC patients. Widely invasive OC was more likely to be SSTR2-positive compared to all other OC subtypes (minimally invasive and angioinvasive) (P = .003). For all patients with OC, TSHR positivity was inversely correlated with SSTR2 positivity (odds ratio, 0.12; CI, 0.03-0.43; P = .006). This relationship was not seen in the patients with OA (odds ratio, 0.30; CI, 0.01-9.14; P = .440). Our results show that recurrent/metastatic OC was more likely to be SSTR2-positive and TSHR-negative than primary OC. Patients with OC displayed a significant inverse relationship between SSTR2 and TSHR expression that was not seen in patients with OA. This may be a key relationship that can be used to prognosticate and treat OCs.

Open Versus Laparoscopic Surgery in the Management of Adrenocortical Carcinoma: A Systematic Review and Meta-analysis.

BACKGROUND: Laparoscopic surgery is considered a standard treatment for benign adrenal tumors; however, no consensus has been reached on the optimal resection technique for adrenocortical carcinomas. This study aims to evaluate the safety and efficacy of laparoscopic surgery and open surgery in the management of adrenocortical carcinoma. METHODS: The Cochrane, Embase, PubMed, Scopus, and Web of Science databases were searched for articles from inception to May 2022, by two independent reviewers using the preferred reporting items for systematic reviews and meta-analysis (PRISMA) guidelines. The review was registered prospectively on the PROSPERO database (CRD42022316050). RESULTS: From 183 studies screened, 11 studies met the eligibility criteria, with a total of 1617 patients with adrenocortical carcinoma undergoing either laparoscopic surgery (n = 472) or open surgery (n = 1145). Open surgery demonstrated a lower rate of positive resection margin compared with laparoscopic surgery (odds ratio [OR] 1.52, 95% confidence interval [CI] 1.10-2.10; I2 = 0%). Additionally, open surgery had more favorable overall survival (OR 0.56, 95% CI 0.44-0.72; I2 = 0%) and recurrence-free rates (OR 0.60, 95% CI 0.42-0.85; I2 = 38%) than laparoscopic surgery at 3 years. Hospital stay was shorter for laparoscopic surgery than open surgery (mean difference - 2.49 days, 95% CI - 2.95 to - 2.04; I2 = 45%). CONCLUSIONS: Open surgery should still be considered the standard operative approach; however, laparoscopic surgery could be regarded as an effective and safe operation for selected adrenocortical carcinoma cases with appropriate laparoscopic expertise. Further randomized controlled studies with tumor stage- and resection margin-dependent survival analysis are necessary to ascertain the safety and efficacy of the treatment.

Association Between Surgical Indication and Outcomes for Outpatient Adrenalectomy.

INTRODUCTION: Despite a favorable risk-benefit profile, inpatient admission postoperatively for minimally invasive adrenalectomy (MIA) has remained common. Prior studies have shown that outpatient MIA was not associated with an increased 30-day complications or readmission. However, this has not been explored in-depth by adrenalectomy indication. We aimed to examine whether the safety profile of outpatient MIA varies by adrenal indication. MATERIALS AND METHODS: Clinicopathologic parameters were examined for all MIAs entered into an adrenal database at our institution from 2012 to 2021. Predictor variables included patient demographics, surgical indication, and operative time. Outcomes were 30-day emergency department visit, readmission, and complication rates between surgical indications, comparing outpatient and inpatient groups. Statistical analyses were performed using Kruskal-Wallis, Wilcoxon, Mann-Whitney, and Chi-squared tests, as appropriate. RESULTS: A total of 185 MIA patients were included. Outpatient MIA was performed in 53 patients (28.6%). Outpatient discharge post-MIA was related to both surgical indication and operative time. Pheochromocytoma (PC) patients were less likely to be discharged as an outpatient postoperatively when compared to all other indications (13.0% versus 33.8%, P = 0.007). Among all patients with operations 2-3 h in length, PC patients were less likely to be discharged home as an outpatient (10% versus 33.3%, P = 0.040). No significant differences were identified between outpatient and inpatient MIA groups for complications, emergency department visits, or readmission (P > 0.05 for all). Only six outpatient MIA patients had any complication (11.3%) and six were readmitted (11.3%). CONCLUSIONS: Outpatient MIA was demonstrated to be associated with similar, low complication and readmission rates compared to inpatient MIA, although it was used less often for patients with PC or prolonged operative times. Our study highlights potential evidence that outpatient MIA can be safely used in selected patients across all indications for adrenal surgery.

Time to Symptom Resolution After Total Thyroidectomy for Graves' Disease.

INTRODUCTION: Total thyroidectomy (TT) has been shown to be a safe and effective treatment for Graves' disease. However, the time course for improvement of symptoms has not been defined. METHODS: With an institutional review board approval, we prospectively gathered survey data of all patients (n = 79) undergoing TT for Graves' disease at a single institution from 2019 to 2021. After informed consent was obtained, patients completed surveys preoperatively and at 2 wk followed by monthly postoperative visits/phone calls. Patient demographics and survey results were collected and analyzed. Symptom recovery time was evaluated using Kaplan-Meier analysis. RESULTS: A total of 50 patients completed the survey on postoperative follow-up (response rate 63%). Average age was 38 y (range 12-80 y) and 88% of patients were female. The most common preoperative symptoms were fatigue (90%) and heat/cold intolerance (88%). Tremor (median time to resolution: 1 wk; interquartile range [IQR] 1-3), diarrhea (median 1 wk [IQR 1-3]), and palpitations (median 1 wk [IQR 1-3]) resolved the most rapidly followed by eye symptoms (median 3 wk [IQR 1-6]), heat/cold intolerance (median 3 wk [IQR 3-30]), memory deficits (median 3 wk [IQR 1-undefined]), and fatigue (median: 3 wk [IQR 1-14]). There were no significant differences in time to resolution of symptoms by gender or age (less than versus 40 y and older). Those with uncontrolled Graves' had more severe symptoms but no difference in time to resolution from the euthyroid Graves' patients. CONCLUSIONS: Many Graves' disease symptoms improve rapidly following TT, with a median time to improvement of less than 1 mo.

Getting Your Foot in the Door: Access to Surgical Care for Thyroid Disease.

INTRODUCTION: Access to specialty care can be challenging for patients, often involving multiple evaluations, laboratory tests, and referrals. To better understand the different pathways to specialty care, we examined the outcomes of patients evaluated for surgical thyroid disease at a single tertiary referral clinic. METHODS: We reviewed 691 patients seen in the endocrine surgery clinic for thyroid disease (2018-2021). Patient demographics, referral source, referral reason, and reason for not receiving an operation were collected. The number of days from referral to initial clinic visit and from initial clinic visit to an operation were also collected. The Chi-square test, the independent t-test, the Kruskal-Wallis test, the Dunn-Bonferroni post hoc test, and multiple logistic regression tests were performed using SPSS. RESULTS: The top reasons for referral were thyroid nodules (54.4%), hyperthyroidism (26.5%), and multinodular goiter (10.3%). Specialty clinic referrals came from endocrinologists (56.0%), self-referrals (15.5%), and primary care physicians (PCP; 14.4%). Self-referred patients had a shorter waiting time for an appointment than those referred by endocrinologists and PCPs. [median (IQR) (days) 12 (6-17) versus 16 (9-24) versus 16 (9-25), P < 0.001]. Overall, 450 (72.7%) patients underwent thyroid surgery. For those who underwent thyroidectomy, self-referred patients had a shorter time between initial clinic visit and the operation compared to those referred by endocrinologists and PCPs [median (IQR) (days) 2 (1-19) versus 19 (8-33) versus 16 (1-48), P < 0.001]. Patients referred for hyperthyroidism (odds ratio [OR] = 2.2, 95% confidence interval [CI] 1.3-10.5, P = 0.012 were more likely to undergo an operation than those referred for other reasons. CONCLUSIONS: Access to specialty care for thyroid disease is facilitated and optimized when self-referrals are permitted. Reducing or eliminating the requirement for a provider referral may improve patients' access.