Next-Generation Sequencing in Sporadic Medullary Thyroid Cancer Patients: Mutation Profile and Disease Aggressiveness.

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.

Vascular stenting of a malignant arterial blowout as a bridge to effective systemic and regional therapy.

Locally advanced cutaneous squamous cell carcinoma can erode into blood vessels, leading to vascular blowout, requiring emergent surgical intervention. We describe a first case of this disease complication which was effectively managed with endovascular stenting as a bridge to effective systemic and regional therapy. We discuss the efficacy of this staged approach which is novel and timely in a clinical environment of increasingly effective systemic therapies.

Decreasing utilization for postoperative radiation therapy in locoregionally advanced medullary thyroid cancer.

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.

Incidence and Geographical Distribution of Adrenocortical Carcinoma: Retrospective Analysis of a State Cancer Registry.

OBJECTIVE: Adrenocortical carcinoma (ACC) is a rare malignancy without established association with environmental risk factors. ACC incidence is stable based on large surgical databases while referral centers data reported increasing number of cases seen. We studied ACC incidence and distribution at a county level to find potential ACC "hot spots" that could be linked to environmental exposures. METHODS: A retrospective analysis of Texas Cancer Registry that included ACC patients diagnosed between 2000 and 2018. County-level heatmaps were created and compared with breast, prostate, and lung cancer. RESULTS: We identified 448 ACC cases during the study period. Cases were registered in 110 of the 254 counties (43.3%) in Texas, representing 92.74% of the total population. The median incidence was 23 new cases/y (range 14-33). The mean population-adjusted ACC incidence rate was 0.104 per 100 000 per year (standard deviation 0.005; 95% CI, 0.092-0.116). Seven counties (6.3%) accounted for 215 (48.0%) cases, with more than 10 cases each and median standardized incidence ratio (SIR) of 0.1 (range, 0.0-0.9). One hundred three counties (93.7%) accounted for the remaining 233 cases (52%), with fewer than 10 cases per county. The highest standardized incidence ratios were found in counties with a median population of fewer than 14 000 residents and with only one reported case. CONCLUSION: Our analysis is the first report to create ACC heatmap and could not detect any geographic clustering of ACC in Texas. The incidence of ACC remained stable and consistent with data from other large databases.

Beyond the three P's: adrenal involvement in MEN1.

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.

Is there a role for liquid biopsy in the surveillance of parathyroid carcinoma?

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.

Melanoma metastatic to the adrenal gland: An update on the role of adrenalectomy in multidisciplinary management.

BACKGROUND AND OBJECTIVES: Modern systemic therapy (immune checkpoint blockade [ICB], targeted therapy) has improved survival for patients with metastatic melanoma. The role of adrenal metastasectomy is not well characterized in this setting. METHODS: Consecutive patients treated with adrenalectomy 1/1/2007-1/1/2019 were retrospectively compared to patients treated with systemic therapy alone in the same time period. Overall survival and survival after adrenal metastasis were compared, prognostic factors associated with survival after adrenal metastasis development were evaluated. RESULTS: A total of 74 patients underwent adrenalectomy and were compared to 69 treated with systemic therapy alone. The most common indications for adrenalectomy were to render the patient disease-free in the setting of isolated adrenal metastasis (n = 32, 43.2%) or treatment of isolated progression in the setting of other stable/responding metastases (n = 32, 43.2%). Patients treated surgically had longer survival (116.9 vs. 11.0 months after adrenal metastasis diagnosis, p < 0.001). On multivariate analysis, receipt of ICB (hazard ratio [HR]: 0.62, 95% confidence interval [CI]: [0.40-0.95]) and selection for adrenalectomy (HR: 0.27, 95% CI: [0.17-0.42]) were the strongest factors associated with improved survival after adrenal metastasis diagnosis. CONCLUSIONS: Selective application of adrenal metastasectomy is associated with prolonged survival benefit and remains an important consideration in the multidisciplinary management of patients with metastatic melanoma.

Adrenal Metastasectomy in the Era of Immuno- and Targeted Therapy.

Adrenal metastasectomy has an increasing role in multimodality oncologic care for diverse primary cancer types. In this review, we discuss the epidemiology, evaluation, and contemporary best practices in the management of adrenal metastases from various primaries. Initial evaluation of suspected adrenal metastases should include diagnostic imaging to assess the extent of tumor involvement and determine surgical resectability, as well as biochemical evaluation for hormone secretion. Biopsy has a minimal role and should only be performed in tumors that are established to be non-hormone secreting and when the biopsy results would change clinical management. Adrenal metastasectomy is associated with survival benefit in selected patients. We suggest that adrenal metastasectomy has the greatest benefit in four clinical scenarios: (1) disease limited to the adrenal gland in which adrenalectomy renders the patient disease-free; (2) isolated progression in the adrenal gland in the setting of otherwise controlled metastatic extra-adrenal disease; (3) need for palliation of symptoms related to adrenal metastases; or (4) in the context of tissue-based clinical trials. Both minimally invasive and open adrenalectomy techniques are safe and appear to have equivalent oncologic outcomes. Minimally invasive approaches are favored when technically feasible while maintaining oncologic principles. A multidisciplinary evaluation including clinicians with expertise in the primary cancer type is essential to the successful management of adrenal metastases.

Advances in Endocrine Surgery.

Recent changes in the landscape of endocrine surgery include a shift from total thyroidectomy for almost all patients with papillary thyroid cancer to the incorporation of thyroid lobectomy for well-selected patients with low-risk disease; minimally invasive parathyroidectomy with, and potentially without, intraoperative parathyroid hormone monitoring for patients with well-localized primary hyperparathyroidism; improvement in the management of parathyroid cancer with the incorporation of immune checkpoint blockade and/or targeted therapies; and the incorporation of minimally invasive techniques in the management of patients with benign tumors and selected secondary malignancies of the adrenal gland.

Pheochromocytoma recurrence in hereditary disease: does a cortical-sparing technique increase recurrence rate?

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.

Parathyroidectomy for Normocalcemic Primary Hyperparathyroidism is Associated with Improved Bone Mineral Density Regardless of Postoperative Parathyroid Hormone Levels.

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.

Neoadjuvant checkpoint inhibitor immunotherapy for resectable mucosal melanoma.

Background: Neoadjuvant checkpoint inhibition (CPI) has recently demonstrated impressive outcomes in patients with stage 3 cutaneous melanoma. However, the safety, efficacy, and outcome of neoadjuvant CPI in patients with mucosal melanoma (MM) are not well studied as MM is a rare melanoma subtype. CPI such as combination nivolumab and ipilimumab achieves response rates of 37-43% in unresectable or metastatic MM but there is limited data regarding the efficacy of these agents in the preoperative setting. We hypothesize that neoadjuvant CPI is a safe and feasible approach for patients with resectable MM. Method: Under an institutionally approved protocol, we identified adult MM patients with resectable disease who received neoadjuvant anti-PD1 +/- anti-CTLA4 between 2015 to 2019 at our institution. Clinical information include age, gender, presence of nodal involvement or satellitosis, functional status, pre-treatment LDH, tumor mutation status, and treatment data was collected. Outcomes include event free survival (EFS), overall survival (OS), objective response rate (ORR), pathologic response rate (PRR), and grade ≥3 toxicities. Results: We identified 36 patients. Median age was 62; 58% were female. Seventy-eight percent of patients received anti-PD1 + anti-CTLA4. Node positive disease or satellite lesions was present at the time of treatment initiation in 47% of patients. Primary sites of disease were anorectal (53%), urogenital (25%), head and neck (17%), and esophageal (6%). A minority of patients did not undergo surgery due to complete response (n=3, 8%) and disease progression (n=6, 17%), respectively. With a median follow up of 37.9 months, the median EFS was 9.2 months with 3-year EFS rate of 29%. Median OS had not been reached and 3-year OS rate was 55%. ORR was 47% and PRR was 35%. EFS was significantly higher for patients with objective response and for patients with pathologic response. OS was significantly higher for patients with pathologic response. Grade 3 toxicities were reported in 39% of patients. Conclusion: Neoadjuvant CPI for resectable MM is a feasible approach with signs of efficacy and an acceptable safety profile. As there is currently no standard approach for resectable MM, this study supports further investigations using neoadjuvant therapy for these patients.

Neoadjuvant relatlimab and nivolumab in resectable melanoma.

Relatlimab and nivolumab combination immunotherapy improves progression-free survival over nivolumab monotherapy in patients with unresectable advanced melanoma1. We investigated this regimen in patients with resectable clinical stage III or oligometastatic stage IV melanoma (NCT02519322). Patients received two neoadjuvant doses (nivolumab 480 mg and relatlimab 160 mg intravenously every 4 weeks) followed by surgery, and then ten doses of adjuvant combination therapy. The primary end point was pathologic complete response (pCR) rate2. The combination resulted in 57% pCR rate and 70% overall pathologic response rate among 30 patients treated. The radiographic response rate using Response Evaluation Criteria in Solid Tumors 1.1 was 57%. No grade 3-4 immune-related adverse events were observed in the neoadjuvant setting. The 1- and 2-year recurrence-free survival rate was 100% and 92% for patients with any pathologic response, compared to 88% and 55% for patients who did not have a pathologic response (P = 0.005). Increased immune cell infiltration at baseline, and decrease in M2 macrophages during treatment, were associated with pathologic response. Our results indicate that neoadjuvant relatlimab and nivolumab induces a high pCR rate. Safety during neoadjuvant therapy is favourable compared to other combination immunotherapy regimens. These data, in combination with the results of the RELATIVITY-047 trial1, provide further confirmation of the efficacy and safety of this new immunotherapy regimen.

Differences in Clinicopathologic Behavior of Oncocytic Adrenocortical Neoplasms and Conventional Adrenocortical Carcinomas.

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.

Management of adrenocorticotropic hormone-secreting neuroendocrine tumors and the role of bilateral adrenalectomy in ectopic Cushing syndrome.

BACKGROUND: Neuroendocrine tumors can cause ectopic Cushing syndrome, and most patients have metastatic disease at diagnosis. We identified risk factors for outcome, evaluated ectopic Cushing syndrome management, and explored the role of bilateral adrenalectomy in this population. METHODS: This was a retrospective study including patients with diagnosis of ectopic Cushing Syndrome secondary to neuroendocrine tumors with adrenocorticotropic hormone secretion treated at our quaternary referral center over a 40-year period (1980-2020). RESULTS: Seventy-six patients were included. Mean age at diagnosis was 46.3 ± 15.8 years. Most patients (N = 61, 80%) had metastases at ectopic Cushing syndrome diagnosis. Average follow-up was 2.9 ± 3.7 years (range, 4 months-17.2 years). Patients with neuroendocrine tumors before ectopic Cushing syndrome had more frequent metastatic disease and resistant ectopic Cushing syndrome. Patients with de novo hyperglycemia, poor neuroendocrine tumor differentiation, and metastatic disease had worse survival. Of those with nonmetastatic disease, 8 (53%) had ectopic Cushing syndrome resolution after neuroendocrine tumor resection, 3 (20%) were medically controlled, and 4 (27%) underwent bilateral adrenalectomy. In patients with metastatic neuroendocrine tumors, hypercortisolism was initially medically managed in 92%, 3% underwent immediate bilateral adrenalectomy, 2% had control after primary neuroendocrine tumor debulking, and 2% were lost to follow-up. Medical treatment resulted in hormonal control in 7 (13%) patients. Of the 49 patients with metastatic disease and medically resistant ectopic Cushing syndrome, 23 ultimately had bilateral adrenalectomy with ectopic Cushing syndrome cure in all. CONCLUSION: Patients with neuroendocrine tumors before ectopic Cushing syndrome development were more likely metastatic and had worse survival. De novo hyperglycemia and poor neuroendocrine tumor differentiation were predictive of worse prognosis. Medical control of hypercortisolism is difficult to achieve in patients with neuroendocrine tumors-ectopic Cushing syndrome. Well-selected patients may benefit from bilateral adrenalectomy early in the treatment algorithm, and multidisciplinary management is essential in this complex disease.

Outcomes After Sphincter-Sparing Local Therapy for Anorectal Melanoma: 1989 to 2020.

PURPOSE: The treatment paradigm for patients with anorectal melanoma eligible for sphincter-sparing excision has evolved over time. This study examines outcomes across a 30-year era in this rare disease with poor prognosis. METHODS AND MATERIALS: This retrospective cohort study included all patients with pelvis-confined anorectal melanoma undergoing sphincter-sparing local excision and adjuvant radiation therapy (RT) at our institution between 1989 and 2020. Patterns of care and predictors of outcome were evaluated. RESULTS: Of the 108 patients included, 92 (85%) presented with clinically uninvolved nodes. For clinically node-negative patients, the sentinel lymph node biopsy rate increased from 18/43 (42%) before 2008 to 38/49 (78%) subsequently and the use of inguinal nodal RT decreased from 33/35 (94%) before 2003 to 1/57 (2%) subsequently. All clinically node-positive patients treated before 2003 received inguinal nodal RT, whereas no node-positive patient treated subsequently received this treatment. Patients treated before 2016 mostly received biochemotherapy, and those treated since 2017 mostly received immune checkpoint inhibitors. With median follow-up of 32 months, 77 patients (71%) recurred. Three-year actuarial outcomes were 84% local control, 64% nodal control, 38% distant metastasis-free survival, 30% disease-free survival, and 51% melanoma-specific survival. Ostomy-free survival at last follow-up was 95%. Factors contributing to outcome were identified. Outcomes for patients treated in the contemporary era (2017+) were not significantly better than those treated earlier. CONCLUSIONS: Sphincter-sparing surgery followed by adjuvant RT results in excellent local control and ostomy-free survival for locally resectable anorectal melanoma. Overall oncologic outcomes continue to be poor, reinforcing the need to identify more effective therapies.

Recurrence after successful parathyroidectomy-Who should we worry about?

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.

Utilization and evolving prescribing practice of opioid and non-opioid analgesics in patients undergoing lymphadenectomy for cutaneous malignancy.

BACKGROUND AND OBJECTIVES: Opioids are commonly prescribed following surgery and can lead to persistent opioid use. We assessed changes in prescribing practices following an opioid education initiative for patients undergoing lymphadenectomy for cutaneous malignancy. METHODS: A single-institution retrospective study of all eligible patients (3/2016-3/2020) was performed. RESULTS: Indications for lymphadenectomy in 328 patients were metastatic melanoma (84%), squamous cell carcinoma (10%), and Merkel cell carcinoma (5%). At discharge, non-opioid analgesics were increasingly utilized over the 4-year study period, with dramatic increases after education initiatives (32%, 42%, 59%, and 79% of pts, respectively each year; p < 0.001). Median oral morphine equivalents (OMEs) prescribed also decreased dramatically starting in year 3 (250, 238, 150, and 100 mg, respectively; p < 0.001). Patients discharged with 200 mg OMEs were less likely to also be discharged with non-opioid analgesics (40% vs. 64%. respectively, p < 0.001). CONCLUSIONS: Analgesic prescribing practices following lymphadenectomy for cutaneous malignancy improved significantly over a 4-year period, with use of non-opioids more than doubling and a 60% reduction in median OME. Opportunities exist to further increase non-opioid use and decrease opioid dissemination after lymphadenectomy for cutaneous malignancy.