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1.
J Endocr Soc ; 8(6): bvae048, 2024 Apr 06.
Article in English | MEDLINE | ID: mdl-38660141

ABSTRACT

Context: Next-generation sequencing (NGS) analysis of sporadic medullary thyroid carcinoma (sMTC) has led to increased detection of somatic mutations, including RET M918T, which has been considered a negative prognostic indicator. Objective: This study aimed to determine the association between clinicopathologic behavior and somatic mutation identified on clinically motivated NGS. Methods: In this retrospective cohort study, patients with sMTC who underwent NGS to identify somatic mutations for treatment planning were identified. Clinicopathologic factors, time to distant metastatic disease (DMD), disease-specific survival (DSS), and overall survival (OS) were compared between somatic mutations. Results: Somatic mutations were identified in 191 sMTC tumors, including RET M918T (53.4%), other RET codons (10.5%), RAS (18.3%), somatic RET indels (8.9%), and RET/RAS wild-type (WT) status (8.9%). The median age at diagnosis was 50 years (range, 11-83); 46.1% were female. When comparing patients with RET M918T, RET-Other, and RET WT (which included RAS and RET/RAS WT), there were no differences in sex, TNM category, systemic therapy use, time to DMD, DSS, or OS. On multivariate analysis, older age at diagnosis (HR 1.05, P < .001; HR 1.06, P< .001) and M1 stage at diagnosis (HR 3.17, P = .001; HR 2.98, P = .001) were associated with decreased DSS and OS, respectively, but mutation cohort was not. When comparing RET M918T to RET indels there was no significant difference in time to DMD, DSS, or OS between the groups. Conclusion: Somatic RET mutations do not portend compromised DSS or OS in a cohort of sMTC patients who underwent clinically motivated NGS.

2.
Article in English | MEDLINE | ID: mdl-38441533

ABSTRACT

CONTEXT: Sporadic medullary thyroid carcinoma (sMTC) rarely occurs in childhood and no studies have specifically focused on this entity. OBJECTIVE: To describe the clinical presentations and long-term outcomes of a large cohort of children and young adults with sMTC compared with hereditary MTC (hMTC). METHODS: Retrospective study of 144 patients diagnosed with MTC between 1961-2019 at an age ≤21 years and evaluated at a tertiary referral center. RESULTS: In contrast to hMTC (n=124/144, 86%), patients with sMTC (n=20/144, 14%) are older (p<0.0001), have larger tumors (p<0.0001), a higher initial stage grouping (p=0.001) and have more structural disease (p=0.0045) and distant metastases (DM) (p=0.00084) at last follow up, but are not more likely to die from MTC (p=0.42). Among 77 patients diagnosed clinically, not by family history (20/20 sMTC and 57/124 hMTC), there was no difference in the initial stage (p=0.27), presence of DM at diagnosis (p=1.0), disease status at last follow-up (p=0.13), overall survival (p=0.57), or disease specific survival (p=0.87). Of the twelve sMTC tumors that underwent somatic testing, eleven (91%) had an identifiable alteration: ten RET gene alterations and one ALK fusion. CONCLUSIONS: sMTC is primarily a RET-driven disease that represents 14% of childhood-onset MTC in this cohort. Pediatric sMTC patients are older, present with clinical disease at a more advanced TNM classification, and have more persistent disease at last follow up compared with hMTC, but these differences disappear when comparing those presenting clinically. Somatic molecular testing should be considered in sMTC patients who would benefit from systemic therapy.

4.
Head Neck ; 46(2): 328-335, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38009416

ABSTRACT

BACKGROUND: Use of postoperative radiation therapy (PORT) in locoregionally advanced medullary thyroid cancer (MTC) remains controversial. The objective was to evaluate the effect of PORT on locoregional control (LRC) and overall survival (OS). METHODS: Retrospective cohort study of 346 MTC patients separated into PORT and no-PORT cohorts. Relative indications for PORT, as well as changes in patterns of treatment, were recorded. RESULTS: 49/346 (14%) received PORT. PORT was associated with worse OS; adjusted HR = 2.0 (95%CI 1.3-3.3). PORT was not associated with improved LRC, even when adjusting for advanced stage (Stage III p = 0.892; Stage IV p = 0.101). PORT and targeted therapy were not associated with improved OS compared to targeted therapy alone; adjusted HR = 1.2 (95%CI 0.3-4.1). CONCLUSIONS: Use of PORT in MTC has decreased and its indications have become more selective, coinciding with the advent of effective targeted therapies. Overall, PORT was not associated with improved LRC or OS.


Subject(s)
Carcinoma, Neuroendocrine , Thyroid Neoplasms , Humans , Retrospective Studies , Thyroid Neoplasms/radiotherapy , Thyroid Neoplasms/surgery , Carcinoma, Neuroendocrine/radiotherapy , Carcinoma, Neuroendocrine/surgery , Neoplasm Staging , Radiotherapy, Adjuvant
5.
Endocr Relat Cancer ; 31(2)2024 Feb 01.
Article in English | MEDLINE | ID: mdl-38108666

ABSTRACT

Adrenal lesions (ALs) are often detected in patients with multiple endocrine neoplasia type 1 (MEN1). However, they are not well described in MEN1, making their clinical management unclear. This study examined the prevalence and outcomes of ALs found in MEN1. We performed a retrospective chart review of patients diagnosed with MEN1 from 1990 to 2021. ALs were diagnosed using abdominal or thoracic imaging and classified as being unilateral or bilateral, having single or multiple nodules, and as having diffuse enlargement or not. Measurable nodular lesions were analyzed for their size and growth over time. Patients' clinical and radiographic characteristics were collected. We identified 382 patients with MEN1, 89 (23.3%) of whom had ALs. The mean age at detection was 47 ± 11.9 years. We documented 101 measurable nodular lesions (mean size, 17.5 mm; range, 3-123 mm). Twenty-seven nodules (26.7%) were smaller than 1 cm. Watchful waiting was indicated in 79 (78.2%) patients, of whom 28 (35.4%) had growing lesions. Functional lesions were diagnosed in 6 (15.8%) of 38 that had functional work-up (diagnoses: pheochromocytoma (n = 2), adrenocorticotropic hormone-dependent hypercortisolism (n = 2), hyperandrogenism (n = 1), hyperaldosteronism (n = 1)); surgery was indicated for 5 (83.3%; n = 12 nodules), 2 of whom had bilateral, diffuse adrenal enlargement. Two patients were diagnosed with adrenocortical carcinoma and two with neoplasms of uncertain malignant potential. Radiographic or clinical progression of ALs is uncommon. Malignancy should be suspected on the basis of a lesion's growth rate and size. A baseline hormonal work-up is recommended, and no further biochemical work-up is suggested when the initial assessment shows nonfunctioning lesions.


Subject(s)
Adrenal Cortex Neoplasms , Adrenal Gland Neoplasms , Adrenocortical Carcinoma , Multiple Endocrine Neoplasia Type 1 , Humans , Adult , Middle Aged , Multiple Endocrine Neoplasia Type 1/pathology , Retrospective Studies , Adrenal Gland Neoplasms/epidemiology
6.
Surgery ; 175(1): 193-198, 2024 01.
Article in English | MEDLINE | ID: mdl-37993289

ABSTRACT

BACKGROUND: Parathyroid carcinoma is a rare malignancy with high recurrence rates. Liquid biopsy is a stratifying tool in disease recurrence/progression in other malignant processes. This study sought to assess the feasibility and application of liquid biopsy in parathyroid carcinoma and its impact on surveillance. METHODS: Retrospective review of a prospectively maintained database of adults treated for parathyroid carcinoma at a tertiary care center (2017-2023). Demographics, clinical characteristics, and laboratory variables were collected. Circulating cell-free deoxyribonucleic acid enrichment and circulating tumor cell enumeration were obtained from serial blood samples. RESULTS: A total of 25 patients were identified-64% were male patients, with a median age of 56 years (interquartile range 45-63). Fifty blood samples were collected postoperatively. At first, circulating tumor cell enumeration, 56% (14/25) of patients had no evidence of disease, and 32% (8/25) had distant metastasis. Median follow-up was 53 months (interquartile range 23-107). At the last follow-up, 40% (10/25) of patients were found to have distant metastasis. Serial circulating tumor cell enumeration was performed in 52% of patients, median highest circulating tumor cell was (interquartile range 1-22). Circulating cell-free deoxyribonucleic acid was assessed in 64% of patients (16/25). There was no difference in circulating tumor cells or circulating cell-free deoxyribonucleic acid between those with distant metastasis and those without distant metastasis. The most common mutation identified was TP53, present in 88% of circulating cell-free deoxyribonucleic acid samples with a mutation. Circulating cell-free deoxyribonucleic acid and parathyroid hormone levels were not found to have any association (r = -0.27, P = .39), but parathyroid hormone and circulating tumor cell had a linear relationship (r = 0.76, P < .001). CONCLUSION: Liquid biopsy appears to be a feasible tool in parathyroid carcinoma surveillance. The relationship between circulating cell-free deoxyribonucleic acid and parathyroid hormone levels remains unclear, and the association between circulating tumor cell enumeration and parathyroid hormone levels may be impactful. The finding that TP53 mutation is more prevalent in patients with distant metastasis may impact further management.


Subject(s)
Cell-Free Nucleic Acids , Neoplastic Cells, Circulating , Parathyroid Neoplasms , Adult , Humans , Male , Middle Aged , Female , Neoplastic Cells, Circulating/pathology , Parathyroid Neoplasms/surgery , Parathyroid Neoplasms/pathology , Neoplasm Recurrence, Local/surgery , Liquid Biopsy , Parathyroid Hormone
8.
Surgery ; 173(1): 26-34, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36229248

ABSTRACT

BACKGROUND: Posterior retroperitoneoscopic adrenalectomy is an appealing approach for patients with hereditary pheochromocytoma and lends well to cortex preservation. We sought to examine pheochromocytoma recurrence in patients with hereditary pheochromocytoma in the era of posterior retroperitoneoscopic adrenalectomy and evaluate the predictors of recurrence. METHODS: Patients with hereditary pheochromocytoma who underwent adrenalectomy for pheochromocytoma between 1995 and 2020 with biochemical cure and follow-up >1 year were identified. Recurrence was defined as plasma metanephrines above the upper limit of normal with radiographic evidence of disease in the ipsilateral adrenal bed. RESULTS: Seventy-eight hereditary pheochromocytoma patients (median age = 32.4 years; 60.3% women) underwent 114 adrenalectomies for pheochromocytoma. Of these patients, 40 had multiple endocrine neoplasia type 2A (51.3%), 10 had multiple endocrine neoplasia type B (12.8%), 17 had von Hippel-Lindau disease (21.8%), and 11 had neurofibromatosis type 1 (14.1%). Thirty-eight adrenalectomies (33.3%) were performed before the introduction of posterior retroperitoneoscopic adrenalectomy and 76 (66.7%) after. Cortical-sparing technique was performed in 62 (54.4%) adrenalectomies, with no difference in its use before and after posterior retroperitoneoscopic adrenalectomy introduction (P > .05). During a median follow-up of 80.7 months (interquartile range 43.4-151.2), 12 ipsilateral recurrences (10.5%) were identified. There was no difference in recurrence before and after the introduction of posterior retroperitoneoscopic adrenalectomy or by surgical technique or approach of the entire cohort (P > .05). Recurrence was more common in those with RET M918T mutation (23.5% vs 8.2%; P = .05). Patients with RET M918T mutations had a shorter recurrence-free survival (P = .013). On multivariate analysis, only RET M918T mutation was independently associated with an increased recurrence risk (hazard ratio = 4.30; 95% confidence interval, 1.26-14.66; P = .019). CONCLUSION: The introduction of posterior retroperitoneoscopic adrenalectomy did not influence the recurrence rate after adrenalectomy for hereditary pheochromocytoma patients. Patients with a RET M918T germline mutation are at increased risk for pheochromocytoma recurrence and may benefit from initial total adrenalectomy.


Subject(s)
Adrenal Gland Neoplasms , Laparoscopy , Multiple Endocrine Neoplasia Type 2a , Pheochromocytoma , Humans , Female , Adult , Male , Retrospective Studies , Pheochromocytoma/genetics , Pheochromocytoma/surgery , Adrenal Gland Neoplasms/genetics , Adrenal Gland Neoplasms/surgery , Adrenalectomy/methods , Multiple Endocrine Neoplasia Type 2a/surgery , Laparoscopy/adverse effects
9.
World J Surg ; 47(2): 363-370, 2023 02.
Article in English | MEDLINE | ID: mdl-36195677

ABSTRACT

BACKGROUND: Biochemical cure in normocalcemic primary hyperparathyroidism (nPHPT) is defined as parathyroid hormone (PTH) level normalization 6 months after parathyroidectomy. However, recent studies show that a significant number of nPHPT patients have persistent PTH elevation postoperatively. We sought to correlate changes in PTH levels with skeletal outcomes after parathyroidectomy in nPHPT patients. METHODS: Adult patients who underwent parathyroidectomy at a tertiary referral center for sporadic PHPT between 2010 and 2020 were reviewed. Pre- and postoperative (6 months, 18 months, and last follow-up) laboratory and bone mineral densities (BMD) were recorded. Primary outcome was 18-month postoperative BMD change in the lumbar spine (LS), total hip (TH) and femoral neck (FN) in normocalcemic and hypercalcemic PHPT (hPHPT) patients. RESULTS: Of 661 patients included, 68 had nPHPT. nPHPT patients frequently had multigland disease (31% vs. 18%, p = 0.014), more bilateral cervical explorations (22% vs. 13%, p = 0.042), and fewer achieved biochemical cure (76% vs. 95%, p < 0.001) than hPHPT patients. Twenty-eight nPHPT patients had BMD data for comparison. Overall, nPHPT patients had improvement in the LS (1.84%, p = 0.002) and TH (1.64%, p = 0.014). When stratified by postoperative PTH levels, nPHPT patients with persistent PTH elevation had more BMD improvement at the TH than those who normalized PTH (3.73% vs. - 0.83%, p = 0.017). There was no difference in improvement at the LS or FN (p = NS). CONCLUSION: Parathyroidectomy is associated with improved BMD in nPHPT patients with bone disease. Although one in four nPHPT patients had elevated postoperative PTH levels persisting throughout the study, BMD improvement was still seen regardless of postoperative PTH level normalization.


Subject(s)
Hypercalcemia , Hyperparathyroidism, Primary , Adult , Humans , Bone Density , Hyperparathyroidism, Primary/complications , Hyperparathyroidism, Primary/surgery , Calcium , Parathyroidectomy , Parathyroid Hormone
10.
Surg Open Sci ; 9: 51-57, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35663797

ABSTRACT

Background: We designed a prospective feasibility study to assess the 5x-multiplier (5x) calculation (eg, 3 pills in last 24 hours × 5 = 15) to standardize discharge opioid prescriptions compared to usual care. Methods: Faculty-based surgical teams volunteered for either 5x or usual care arms. Patients undergoing inpatient (≥ 48 hours) surgery and discharged by surgical teams were included. The primary end point was discharge oral morphine equivalents. Secondary end points were opioid-free discharges and 30-day refill rates. Results: Median last 24-hour oral morphine equivalents was similar between arms (7.5 mg 5x vs 10 mg usual care, P = .830). Median discharge oral morphine equivalents were less in the 5x arm (50 mg 5x vs 75 mg usual care, P < .001). Opioid-free discharges included 33.5% 5x vs 18.0% usual care arm patients (P < .001). Thirty-day refill rates were similar (15.3% 5x vs 16.5% usual care, P = .742). Conclusion: The 5x-multiplier was associated with reduced opioid prescriptions without increased refills and can be feasibly implemented across a diverse surgical practice.

11.
Ann Surg Oncol ; 29(9): 5555-5563, 2022 Sep.
Article in English | MEDLINE | ID: mdl-35499784

ABSTRACT

BACKGROUND: Oncocytic adrenocortical neoplasms (OANs) are rare endocrine tumors that present as a spectrum from benign to malignant. The outcomes after surgical resection of the oncocytic variant of adrenocortical carcinoma remain poorly understood. We sought to characterize the clinicopathologic features of OAN and compare oncocytic adrenocortical carcinoma (OAC) with conventional adrenocortical carcinoma (ACC). PATIENTS AND METHODS: Adult patients who underwent adrenalectomy for OAN or ACC between January 1990 and September 2020 were identified. Demographics, clinicopathologic factors, American Joint Committee on Cancer stage, and cancer-related outcomes were reviewed. A matched cohort analysis of disease-free survival (DFS) and overall survival (OS) was performed between patients with OACs and those with ACCs. RESULTS: Forty-one patients with OAN and 214 patients with ACC were included. The OAN cohort median age was 45.2 years [interquartile ratio (IQR) 38.5-54.0 years], and 61.0% were female. OANs were benign (n = 11), of uncertain malignant potential (UMP, n = 9), or OAC (n = 21). Disease recurrence occurred in 12 (57.1%) patients with OAC compared with 1 (11.1%) and 0 patients with UMP or benign OAN, respectively (p < 0.001). Seven (33.3%) patients with OAC died during follow-up compared with 0 patients with UMP or benign OAN (p = 0.020). Kaplan-Meier survival analysis found no difference in DFS between ACC and OAC groups before (p = 0.218) and after 2:1 matching (p = 0.417). Overall survival was shorter for patients who had ACC compared with those who had OAC (p = 0.031), but the difference was not evident with matched analysis (p = 0.200). CONCLUSIONS: OAN presents as a spectrum from benign indolent tumors to aggressive carcinomas. OACs demonstrate similar clinicopathologic behavior and recurrence-free and overall survival when matched to conventional ACCs.


Subject(s)
Adenocarcinoma , Adrenal Cortex Neoplasms , Adrenocortical Carcinoma , Adult , Female , Humans , Male , Middle Aged , Adenocarcinoma/surgery , Adrenal Cortex Neoplasms/pathology , Adrenalectomy , Adrenocortical Carcinoma/pathology , Neoplasm Recurrence, Local/surgery
12.
Am J Surg ; 223(4): 670-675, 2022 04.
Article in English | MEDLINE | ID: mdl-34315576

ABSTRACT

BACKGROUND: This study investigates the impact of the COVID-19 pandemic on endocrine surgeons. METHODS: A survey on the professional, educational, and clinical impact was sent to active and corresponding members of the American Association of Endocrine Surgeons (AAES) in September 2020. Chi-square and paired t-test were used for analysis. RESULTS: 77 surgeons responded (14.8 %). All reported suspension of elective surgeries; 37.7 % were reassigned to other duties during this time. The median number of cases backlogged was 30 (IQR 15-50). Most surgeons reported decreased clinical volume (74.6 %). The use of virtual platforms for clinical and educational purposes increased from pre-COVID-19 levels (all p < 0.001). Use of in-office procedures (p < 0.001) and length of observation prior to discharge for thyroid surgery (p < 0.05) decreased. CONCLUSION: The COVID-19 pandemic led to suspension of operations and decreased practice volume for endocrine surgeons. Surgeons increased use of virtual platforms, decreased in-office procedures, and decreased duration of observation for thyroid surgery in response.


Subject(s)
COVID-19 , Endocrine Surgical Procedures , Surgeons , COVID-19/epidemiology , Humans , Pandemics , SARS-CoV-2 , Surveys and Questionnaires , United States/epidemiology
13.
J Surg Res ; 270: 279-285, 2022 02.
Article in English | MEDLINE | ID: mdl-34717261

ABSTRACT

BACKGROUND: High-resolution pelvic magnetic resonance imaging (MRI) is a critical tool in the management of patients with rectal cancer. An on-line curriculum was developed for surgical trainees on the interpretation of pelvic MRI in rectal cancer for clinical staging and surgical planning. METHODS: The online curriculum was developed using the six-step approach to curriculum development for medical education. The curriculum incorporated case-based learning, annotated videos, and narrated presentations on key aspects of pelvic MRI in rectal cancer. A pilot study was conducted to assess curriculum effectiveness among Complex General Surgical Oncology (CGSO) fellows using pre- and post-intervention assessments. RESULTS: Of 15 eligible fellows, nine completed the pilot study (60%). The fellows' median confidence score after completing the online curriculum (40, IQR: 33-46) was significantly higher than their baseline median confidence score (23, IQR: 14-30), P = 0.0039. The total practical assessment score significantly increased from a pre-median score of 9 (IQR: 8-11) to a post-median score of 14 (IQR: 13-14), P = 0.0078. A subgroup analysis revealed a significant change in the knowledge assessment with a median score of 7 compared to a baseline median score of 4, Z = 2.64, P = 0.0078. However, the skills assessment showed no significant change. CONCLUSIONS: The case-based online curriculum had a positive impact on CGSO fellows' knowledge and confidence in the utilization of pelvic MRI for patients with rectal cancer. This unique on-line curriculum demonstrates a mechanism to enhance shared educational collaboration across CGSO fellowships and other surgical training programs.


Subject(s)
Rectal Neoplasms , Surgeons , Clinical Competence , Curriculum , Education, Medical, Graduate/methods , Fellowships and Scholarships , Humans , Magnetic Resonance Imaging , Pilot Projects , Rectal Neoplasms/diagnostic imaging , Rectal Neoplasms/surgery
14.
Surgery ; 171(1): 40-46, 2022 01.
Article in English | MEDLINE | ID: mdl-34340820

ABSTRACT

BACKGROUND: Preventing cervical reoperations is important-especially after parathyroidectomy. We sought to examine early predictors of recurrence of primary hyperparathyroidism after surgical cure. METHODS: Adult patients with sporadic primary hyperparathyroidism treated with parathyroidectomy between September 1, 1997, and September 1, 2019, with confirmed eucalcemia at 6 months postoperatively were identified. Recurrence was defined as hypercalcemia (>10.2 mg/dL) with an elevated or nonsuppressed parathyroid hormone level on subsequent follow-up. RESULTS: Parathyroidectomy was performed in 522 patients (median age, 62.1 years, 77% female) with the majority undergoing planned minimally invasive parathyroidectomy (85.4%, n = 446). After a median follow-up of 30.9 months, 13 patients (2.5%) recurred (median time to recurrence 50.2 months, interquartile range 27.9-66.5), all of whom underwent planned minimally invasive parathyroidectomy (n = 13/446, 2.9%). Recurrence was more common in those with higher (but still normal) 6-month calcium (10.1 vs 9.3 mg/dL, P < .001) or parathyroid hormone values (64 vs 46 pg/mL, P < .01). Multivariate analysis revealed that age >66.5 years, calcium ≥9.8mg/dL and parathyroid hormone ≥80 pg/mL at 6 months were associated with increased risk of recurrence. In addition, the presence of at least 1 preoperative imaging study that conflicted with intraoperative findings among minimally invasive parathyroidectomy patients (n = 446) was associated with increased risk of recurrence (hazard ratio 4.93, 95% confidence interval 1.25-16.53, P = .016). CONCLUSION: Recurrence of sporadic primary hyperparathyroidism after initial surgical cure in the era of minimally invasive parathyroidectomy is 2.5%. Identification of those at risk for recurrence using 6-month serum calcium ≥9.8 mg/dL, parathyroid hormone ≥80 pg/mL, and/or potentially conflicting localization studies may inform surveillance strategies.


Subject(s)
Hypercalcemia/surgery , Hyperparathyroidism, Primary/surgery , Minimally Invasive Surgical Procedures/statistics & numerical data , Parathyroidectomy/statistics & numerical data , Aged , Calcium/blood , Female , Follow-Up Studies , Humans , Hypercalcemia/blood , Hypercalcemia/diagnosis , Hypercalcemia/epidemiology , Hyperparathyroidism, Primary/blood , Hyperparathyroidism, Primary/diagnosis , Hyperparathyroidism, Primary/epidemiology , Male , Middle Aged , Parathyroid Hormone/blood , Parathyroidectomy/methods , Recurrence , Retrospective Studies , Risk Assessment/methods , Risk Assessment/statistics & numerical data , Treatment Outcome
15.
Surgery ; 171(5): 1240-1246, 2022 05.
Article in English | MEDLINE | ID: mdl-34952716

ABSTRACT

BACKGROUND: Postoperative hypoparathyroidism from inadequate parathyroid hormone is of concern after multigland resections in multiple endocrine neoplasia type 1-related primary hyperparathyroidism. We evaluated risk factors, long-term outcomes, and roles of autotransplantation and cryopreservation in postoperative hypoparathyroidism in multiple endocrine neoplasia type 1. METHODS: Retrospective cohort study of patients with multiple endocrine neoplasia type 1 and parathyroidectomy who were evaluated at MD Anderson from 1990 to 2020. RESULTS: We included 206 patients. Median follow-up after the last operation (index 65%, reoperation 35%) was 8 years. Index parathyroidectomy was subtotal in 47%, less than subtotal in 42%, and total in 12%; hypoparathyroidism was more frequent after total parathyroidectomy. Forty-seven patients (23%) had hypoparathyroidism ≥6 months; odds were significantly higher when cumulative ≥4 glands were resected (odds ratio 6 [2.96-12.24]) or when immediate postoperative parathyroid hormone was <15 pg/mL (odds ratio 13.10 [3.61-47.47]). After median 26 months postoperatively, 30% recovered parathyroid function spontaneously; this was less likely when ≥4 glands were resected (odds ratio 0.19 [0.05-0.72]). None of the 4 patients who were aparathyroid (parathyroid hormone undetectable or ≤3 pg/mL) at 6 months postoperatively recovered parathyroid function. Immediate autotransplantation success rate was 72%. Cryopreservation was performed in 96 operations with delayed autotransplantation in 10 patients (10% utilization), of whom 5 recovered parathyroid function (time to recovery 12-93 months). CONCLUSION: Odds of prolonged hypoparathyroidism are higher when cumulative ≥4 glands are resected or postoperative parathyroid hormone is <15 pg/mL. Spontaneous recovery occurred but was less likely when ≥4 glands were resected or patients were aparathyroid at 6 months postoperatively. Cryopreservation should be sparingly used, but there is value in select high-risk patients such as reoperative parathyroidectomy/cervical surgery.


Subject(s)
Hypoparathyroidism , Multiple Endocrine Neoplasia Type 1 , Humans , Hypoparathyroidism/etiology , Hypoparathyroidism/prevention & control , Multiple Endocrine Neoplasia Type 1/complications , Multiple Endocrine Neoplasia Type 1/surgery , Neoplasm Recurrence, Local/surgery , Parathyroid Glands/transplantation , Parathyroid Hormone , Parathyroidectomy/adverse effects , Retrospective Studies , Risk Factors , Transplantation, Autologous/adverse effects
16.
Am J Cancer Res ; 11(6): 3227-3239, 2021.
Article in English | MEDLINE | ID: mdl-34249457

ABSTRACT

Activating transcription factor 4 (ATF4) is a crucial mediator of the integrated stress response and a negative regulator of RET tyrosine kinase receptor in medullary thyroid carcinoma (MTC). However, the impact of genomic abnormalities in the ATF4 locus on MTC pathogenesis and response to tyrosine kinase inhibitor therapy remains unknown. Here, we evaluated ATF4 copy number variation and protein levels, with overall survival and response to TKIs in a clinical cohort of fifty-nine sporadic primary MTC. We assessed the somatic RETM918T mutation by sequencing, ATF4 copy number by a real-time polymerase chain reaction, and ATF4 protein levels using immunohistochemistry. This MTC cohort comprised 45 (76%) stage IV patients with a median follow-up of 100 months (interquartile range: 58-134 months). Somatic RETM918T was present in 23/57 (40%) tumors. Mono-allelic (36%; 21/59) and bi-allelic (5%; 3/59) loss of ATF4 was identified and was associated with low ATF4 protein expression (0-20%). Kaplan-Meier curves highlight low ATF4 protein or ATF4 loss alone had a significant negative impact on median survival compared to high protein expression (P<0.001) or diploid ATF4 (P=0.011), respectively. The combination of somatic RETM918T and low ATF4 protein levels further decreased overall survival. Both allelic loss and protein reduction were associated with worse overall survival (HR=3.79, 4.06 +RETM918T , and HR=10.64, 11.66 +RETM918T , respectively). Additionally, all 4 of the 11 patients treated with TKIs with a progressive disease by RECIST had low tumor ATF4 protein, with the two partial responder's tumors having high ATF4 protein. These findings suggest that ATF4 may predict response to tyrosine kinase inhibitors, serve as a prognostic marker for personalized care, and a therapeutic target in MTC.

17.
Endocr Pract ; 27(5): 383-389, 2021 May.
Article in English | MEDLINE | ID: mdl-33840638

ABSTRACT

OBJECTIVE: To understand patient perspective regarding recommended changes in the 2015 American Thyroid Association (ATA) guidelines. Specifically, in regard to active surveillance (AS) of some small differentiated thyroid cancer (DTC), performance of less extensive surgery for low-risk DTC, and more selective administration of radioactive iodine (RAI). METHODS: An online survey was disseminated to thyroid cancer patient advocacy organizations and members of the ATA to distribute to the patients. Data were collected on demographic and treatment information, and patient experience with DTC. Patients were asked "what if" scenarios on core topics, including AS, extent of surgery, and indications for RAI. RESULTS: Survey responses were analyzed from 1546 patients with DTC: 1478 (96%) had a total thyroidectomy, and 1167 (76%) underwent RAI. If there was no change in the overall cancer outcome, 606 (39%) of respondents would have considered lobectomy over total thyroidectomy, 536 (35%) would have opted for AS, and 638 (41%) would have chosen to forego RAI. Moreover, (774/1217) 64% of respondents wanted more time with their clinicians when making decisions about the extent of surgery. A total of 621/1167 of patients experienced significant side effects with RAI, and 351/1167 of patients felt that the risks of treatment were not well explained. 1237/1546 (80%) of patients felt that AS would not be overly burdensome, and quality of life was the main reason cited for choosing AS. CONCLUSION: Patient perspective regarding choice in the management of low-risk DTC varies widely, and a large proportion of DTC patients would change aspects of their care if oncologic outcomes were equivalent.


Subject(s)
Iodine Radioisotopes , Thyroid Neoplasms , Humans , Iodine Radioisotopes/therapeutic use , Quality of Life , Thyroid Neoplasms/radiotherapy , Thyroid Neoplasms/surgery , Thyroidectomy
18.
J Surg Res ; 262: 240-243, 2021 06.
Article in English | MEDLINE | ID: mdl-33549329

ABSTRACT

As the SARS-COV-2 pandemic created the need for social distancing and the implementation of nonessential travel bans, residency and fellowship programs have moved toward a web-based virtual process for applicant interviews. As part of the Society of Asian Academic Surgeons 5th Annual Meeting, an expert panel was convened to provide guidance for prospective applicants who are new to the process. This article provides perspectives from applicants who have successfully navigated the surgical subspecialty fellowship process, as well as program leadership who have held virtual interviews.


Subject(s)
COVID-19/prevention & control , General Surgery/education , Internship and Residency/organization & administration , Personnel Selection/methods , Videoconferencing/organization & administration , COVID-19/epidemiology , COVID-19/transmission , Certification/organization & administration , Certification/standards , Faculty/psychology , Faculty/standards , Fellowships and Scholarships/organization & administration , Fellowships and Scholarships/standards , Humans , Internship and Residency/standards , Leadership , Pandemics/prevention & control , Personnel Selection/organization & administration , Personnel Selection/standards , Physical Distancing , Social Interaction , Specialty Boards , Surgeons/psychology , Surgeons/standards
19.
Surgery ; 169(1): 175-184, 2021 01.
Article in English | MEDLINE | ID: mdl-32703679

ABSTRACT

BACKGROUND: It is unclear whether genotype-negative clinical multiple endocrine neoplasia type 1 patients derive equal benefit from prospective surveillance as genotype-positive patients. METHODS: In this retrospective cohort study, we compared genotype-negative patients with clinical multiple endocrine neoplasia type 1 with genotype-positive index cases. Primary outcome was age-related penetrance of manifestations; secondary outcomes were disease-specific survival and clinical course of endocrine tumors. RESULTS: We included 39 genotype-negative patients with clinical multiple endocrine neoplasia type 1 (Male: 33%) and 63 genotype-positive multiple endocrine neoplasia type 1 index cases (Male: 59%). Genotype-negative patients with clinical multiple endocrine neoplasia type 1 were 65 years old at last follow-up; genotype-positive multiple endocrine neoplasia type 1 index cases were 50 (P < .001). Genotype-negative patients with clinical multiple endocrine neoplasia type 1 were significantly older at their first and second primary manifestation. Only 1 developed a third primary manifestation. No genotype-negative patients with clinical multiple endocrine neoplasia type 1 with primary hyperparathyroidism and a pituitary adenoma developed a duodenopancreatic neuroendocrine tumor. Disease-specific survival was significantly better in genotype-negative patients with clinical multiple endocrine neoplasia type 1. In genotype-negative patients with clinical multiple endocrine neoplasia type 1, primary hyperparathyroidism was single-gland disease in 47% of parathyroidectomies versus 0% in genotype-positive multiple endocrine neoplasia type 1 index cases. In genotype-negative patients with clinical multiple endocrine neoplasia type 1, 17% of duodenopancreatic neuroendocrine tumors were multifocal versus 68% in genotype-positive multiple endocrine neoplasia type 1 index cases. Genotype-negative patients with clinical multiple endocrine neoplasia type 1 had more pituitary macroadenomas, fewer prolactinomas, and more somatotroph adenomas. CONCLUSION: Genotype-negative patients with clinical multiple endocrine neoplasia type 1 have a different clinical course than genotype-positive multiple endocrine neoplasia type 1 index cases. This may support a separate classification and a tailored surveillance regimen. Of the genotype-negative patients with clinical multiple endocrine neoplasia type 1 who had parathyroidectomy, almost half had no evidence of multigland disease and may be potential candidates for a more targeted single-gland approach.


Subject(s)
Hyperparathyroidism, Primary/epidemiology , Multiple Endocrine Neoplasia Type 1/therapy , Neuroendocrine Tumors/epidemiology , Pancreatic Neoplasms/epidemiology , Pituitary Neoplasms/epidemiology , Adult , Age Factors , Aged , Female , Follow-Up Studies , Genetic Testing/statistics & numerical data , Genotype , Humans , Hyperparathyroidism, Primary/genetics , Hyperparathyroidism, Primary/therapy , Kaplan-Meier Estimate , Male , Middle Aged , Multiple Endocrine Neoplasia Type 1/complications , Multiple Endocrine Neoplasia Type 1/genetics , Multiple Endocrine Neoplasia Type 1/mortality , Neuroendocrine Tumors/genetics , Neuroendocrine Tumors/therapy , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/therapy , Parathyroidectomy/statistics & numerical data , Pituitary Neoplasms/genetics , Pituitary Neoplasms/therapy , Proto-Oncogene Proteins/genetics , Retrospective Studies , Risk Factors , Watchful Waiting
20.
Am J Surg ; 222(1): 99-103, 2021 07.
Article in English | MEDLINE | ID: mdl-33189309

ABSTRACT

BACKGROUND: The COVID crisis hit during the interview season for the Complex General Surgical Oncology (CGSO) fellowship. With minimal time to adapt, all programs transitioned to virtual interviews. Here we describe the experience of both program directors (PDs) and candidates with virtual interviews, and provide guidelines for implementation based on the results. METHODS: Surveys regarding interview day specifics and perceptions were created for CGSO fellowship PDs and candidates. They were distributed at the conclusion of the season, prior to match. RESULTS: Thirty (94%) PDs and 64 (79%) candidates responded. Eighty-three% of PDs and 79% of candidates agreed or strongly agreed that they felt comfortable creating a rank list. If given the choice, 60% of PDs and 45% of candidates would choose virtual interviews over in-person interviews. The majority of candidates found PD overviews, fellows only sessions and pre-interview materials helpful. CONCLUSION: Overall, the majority of PDs and candidates felt comfortable creating a rank list; however, more PDs preferred virtual interviews for the future. Our results also confirm key components of a virtual interview day.


Subject(s)
Internship and Residency/organization & administration , Personal Satisfaction , Personnel Selection/methods , Surgical Oncology/education , Telecommunications/organization & administration , Adult , COVID-19/epidemiology , COVID-19/prevention & control , Communicable Disease Control/standards , Female , Humans , Internship and Residency/methods , Internship and Residency/statistics & numerical data , Male , Pandemics/prevention & control , Personnel Selection/organization & administration , Personnel Selection/standards , Personnel Selection/statistics & numerical data , Surgeons/psychology , Surgeons/statistics & numerical data , Surgical Oncology/organization & administration , Surgical Oncology/standards , Surveys and Questionnaires/statistics & numerical data , Telecommunications/standards , Telecommunications/statistics & numerical data
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