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INTRODUCTION: Elevated metanephrine and catecholamine levels 3-fold upper limit of normal (ULN) are diagnostic for pheochromocytoma. We sought to determine whether size correlates with biochemical activity or symptoms which could guide timing of surgery. METHODS: Data from consecutive patients undergoing adrenalectomy for pheochromocytoma at our institution over a 10-year period were retrospectively collected. These included maximal lesion diameter on preoperative imaging, plasma/urine metanephrine and/or catecholamine levels, demographic variables and presence of typical paroxysmal symptoms. Receiver operating characteristic curves were used to assess predictive accuracy. RESULTS: Sixty-three patients were included in the analysis (41 females and 22 males). Median age was 56 (43, 69) years. Due to various referring practices, 31 patients had documented 24-h urine metanephrine, 26 had 24-h urine catecholamine, and 52 had fractionated plasma metanephrine levels available for review. Values were converted to fold change compared to ULN and the maximum of all measured values was used for logistic regression. Median tumor size was 3.40 (2.25, 4.55) cm in greatest dimension. Tumor size at which pheochromocytoma produced > 3-fold ULN was ≥2.3 cm (AUC of 0.84). Biochemical activity increased with doubling tumor size (odds ratio = 8, P = 0.0004) or ≥ 1 cm increase in tumor size (odds ratio = 3.03, P = 0.001). 40 patients had paroxysmal symptoms, but there was no significant correlation between tumor size/biochemical activity and symptoms. CONCLUSIONS: In our study, tumor size directly correlated with the degree of biochemical activity and pheochromocytomas ≥2.3 cm produced levels 3 times ULN. These findings may allow clinicians to adjust timing of operative intervention.
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Neoplasias de las Glándulas Suprarrenales , Adrenalectomía , Metanefrina , Feocromocitoma , Humanos , Feocromocitoma/cirugía , Feocromocitoma/patología , Feocromocitoma/sangre , Femenino , Masculino , Persona de Mediana Edad , Neoplasias de las Glándulas Suprarrenales/cirugía , Neoplasias de las Glándulas Suprarrenales/patología , Neoplasias de las Glándulas Suprarrenales/sangre , Estudios Retrospectivos , Adulto , Anciano , Metanefrina/orina , Metanefrina/sangre , Catecolaminas/orina , Catecolaminas/sangre , Carga Tumoral , Relevancia ClínicaRESUMEN
Pancreatic neuroendocrine tumors originate from hormone-producing islet cells and have a propensity to metastasize to the liver once they reach 2 cm in size. Their diagnosis relies upon a combination of computed tomography, MRI, DOTATATE PET, and endoscopic ultrasound with or without tissue biopsy. Biochemical work-up is driven by patient symptoms of hormone excess.
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Tumores Neuroendocrinos , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/diagnóstico por imagen , Tumores Neuroendocrinos/diagnóstico , Tumores Neuroendocrinos/diagnóstico por imagen , Endosonografía/métodos , Tomografía Computarizada por Rayos X/métodos , Imagen por Resonancia Magnética/métodosRESUMEN
CONTEXT: Medullary thyroid cancer has a historic recurrence rate up to 50%, and surgery remains the only cure. OBJECTIVE: This study aims to assess factors related to recurrence and metastatic spread in MTC. DESIGN: Retrospective chart review was performed from 1990-2023. Descriptive analysis and regression models were used for analysis. SETTING: Single specialized tertiary care referral center. PATIENTS: 68 patients with MTC, who underwent surgery, were included. MAIN OUTCOME MEASURE: Recurrence. RESULTS: Mean age at diagnosis was 54.9years(42.2-64.1), 65%(n=44) females. Lymph node and distant metastases were found in 24%(n=16) and 4%(n=3), respectively. RET mutations were present in 52%(n=35): MTC risk levels Highest 6%, High 7%, and Moderate 39%. Mean tumor size was 1.9cm(1.2-3.2) and mean preoperative calcitonin was 504.4pg/mL(133.2-1833.8). Total thyroidectomy(TT) was performed in 10 patients, TT+central neck dissection(CND) in 28, and TT+CND+lateral neck dissection(LND) in 25. On final pathology, 40% had positive central nodes and 25% had positive lateral nodes. Recurrence was 22%, median follow-up 4.7years(1.2-28.0). Male gender(HR=5.81, p=0.021), positive lateral neck nodes(HR 8.10, p=0.011) and high/highest MTC risk level RET mutations(HR 8.66, p=0.004) were significantly associated with recurrence. Preoperative calcitonin>2,175 pg/mL was a strong predictor for distant metastasis(AUC0.893) and a good predictor for lateral neck disease(AUC0.706). Extent of surgery was not significantly associated with recurrence(p=0.634). CONCLUSION: One of 4 patients undergoing surgery for MTC will recur. Risk factors associated with recurrence are male gender, lateral LN metastasis and high/highest MTC risk level mutations, but not necessarily surgery type. Preoperative calcitonin>2,175 pg/mL is suggestive of advanced disease and should prompt further evaluation.
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BACKGROUND: Molecular testing guides the management of cytologically indeterminate thyroid nodules. We evaluated the real-world clinical benefit of a commercially available thyroid mutation panel plus microRNA risk classifier in classifying RAS-mutated nodules. METHODS: We performed a subgroup analysis of the results of molecular testing of Bethesda III/IV nodules using the ThyGenX/ThyGeNEXT-ThyraMIR platform at 3 tertiary-care centers between 2017 and 2021, defining a positive result as 10% or greater risk of malignancy. RESULTS: We identified 387 nodules from 375 patients (70.7% female, median age 59.3 years) who underwent testing. Positive nodules (32.3%) were associated with increased surgical intervention (74.4% vs 14.9%, P < .0001) and carcinoma on surgical pathology (46.4% vs 3.4%, P < .0001) compared to negative modules. RAS mutations were the most common mutations, identified in 71 of 380 (18.7%) nodules, and were classified as ThyraMIR- (28 of 71; 39.4%) or ThyraMIR+ (43 of 71; 60.6%). Among RAS-mutated nodules, there was no significant difference in operative rate (P = .2212) or carcinoma diagnosis (P = .6277) between the ThyraMIR+ and ThyraMIR- groups, and the sensitivity, specificity, negative predictive value, and positive predictive value of ThyraMIR were 64.7%, 34.8%, 40.0%, and 59.5%, respectively. CONCLUSION: Although testing positive is associated with malignancy in surgical pathology, the ThyraMIR classifier failed to differentiate between benign and malignant RAS-mutated nodules. Diagnostic lobectomy should be considered for RAS-mutated nodules, regardless of microRNA expression status.
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Carcinoma , MicroARNs , Neoplasias de la Tiroides , Nódulo Tiroideo , Humanos , Femenino , Persona de Mediana Edad , Masculino , Nódulo Tiroideo/diagnóstico , Nódulo Tiroideo/genética , Nódulo Tiroideo/cirugía , MicroARNs/genética , Neoplasias de la Tiroides/diagnóstico , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/cirugía , Mutación , Estudios RetrospectivosRESUMEN
CONTEXT: Pancreatic neuroendocrine tumors (PNETs) exhibit a wide range of behavior from localized disease to aggressive metastasis. A comprehensive transcriptomic profile capable of differentiating between these phenotypes remains elusive. OBJECTIVE: Use machine learning to develop predictive models of PNET metastatic potential dependent upon transcriptomic signature. METHODS: RNA-sequencing data were analyzed from 95 surgically-resected primary PNETs in an international cohort. Two cohorts were generated with equally balanced metastatic PNET composition. Machine learning was used to create predictive models distinguishing between localized and metastatic tumors. Models were validated on an independent cohort of 29 formalin-fixed, paraffin-embedded samples using NanoString nCounter®, a clinically-available mRNA quantification platform. RESULTS: Gene expression analysis identified concordant differentially expressed genes between the two cohorts. Gene set enrichment analysis identified additional genes that contributed to enriched biologic pathways in metastatic PNETs. Expression values for these genes were combined with an additional 7 genes known to contribute to PNET oncogenesis and prognosis, including ARX and PDX1. Eight specific genes (AURKA, CDCA8, CPB2, MYT1L, NDC80, PAPPA2, SFMBT1, ZPLD1) were identified as sufficient to classify the metastatic status with high sensitivity (87.5% - 93.8%) and specificity (78.1% - 96.9%). These models remained predictive of the metastatic phenotype using NanoString nCounter® on the independent validation cohort, achieving a median AUROC of 0.886. CONCLUSIONS: We identified and validated an eight-gene panel predictive of the metastatic phenotype in PNETs, which can be detected using the clinically-available NanoString nCounter® system. This panel should be studied prospectively to determine its utility in guiding operative versus non-operative management.