RESUMEN
BACKGROUND: Liver metastasis from duodenopancreatic neuroendocrine neoplasms (DP-NENs) is a major cause of mortality in multiple endocrine neoplasia type 1 (MEN1) patients, yet much of their natural history is unknown. METHODS: This longitudinal, retrospective cohort study analyzed all MEN1 patients with imageable functional (F) and nonfunctional (NF) DP-NENs (1990-2021) for liver metastasis-free survival (LMFS) and overall survival (OS). RESULTS: Of 138 patients, 85 (61.6%) had imageable DP-NENs (28 F, 57 NF), and the mean largest tumor size was 1.8 ± 1.4 cm. Multifocality was present in 32 patients (37.7%). Surgery was performed for 49 patients (57.7%). During an 11-year median follow-up period (IQR, 6-17 years), 23 (27.1%) of the patients had liver metastasis, and 19 (22.4%) patients died. Death was attributed to liver metastasis in 60% of cases. The patients with F-DP-NENs versus NF-DP-NENs more often had liver metastasis (46.4% vs. 15.8%; p = 0.002) but had similar 10-year LMFS (80.9 vs. 87.0%; p = 0.44) and OS (82.7 vs. 94.3%; p = 0.69). The patients with NF-DP-NENs had surgery when their tumors were larger (p < 0.001). Tumor size was not associated with liver metastasis (p = 0.89). The average growth rate was 0.04 cm/year (SE, 0.02 cm/year; p = 0.01) during active surveillance for NF-DP-NENs (n = 38). Liver metastasis developed in four patients with tumors smaller than 2 cm. The risk of liver metastasis was independent of surgery (hazard ratio [HR], 0.78; 95% confidence interval [CI], 0.21-2.93; p = 0.72) and death (HR, 0.51; 95% CI, 0.08-3.06; p = 0.46). CONCLUSIONS: Although the observed outcomes in this study were better than historical data, small NF-DP-NENs still developed liver metastasis and liver metastasis remains a major cause of death. These results suggest that size as a sole criterion for surgery may be insufficient to predict tumor behavior.
Asunto(s)
Neoplasias Hepáticas , Neoplasia Endocrina Múltiple Tipo 1 , Tumores Neuroendocrinos , Neoplasias Pancreáticas , Humanos , Neoplasias Hepáticas/secundario , Neoplasia Endocrina Múltiple Tipo 1/complicaciones , Neoplasia Endocrina Múltiple Tipo 1/cirugía , Tumores Neuroendocrinos/patología , Neoplasias Pancreáticas/patología , Estudios RetrospectivosRESUMEN
BACKGROUND: Risk stratification for patients with differentiated thyroid cancer (DTC) is based primarily on pathologic tumor characteristics. Accurate preoperative prognostication could allow for more informed initial surgical recommendations, particularly among patients at a higher risk for distant metastasis (DM). The objective of this study was to characterize the genetic profile of DTC with DM and to validate a molecular-based risk stratification. METHODS: A case-control study design was used to analyze patients who had DTC with DM (n = 62) and a propensity matched cohort of patients who had DTC without DM after at least 5 years of follow-up using the ThyroSeq version 3 targeted next-generation sequencing assay. The results were classified into high-risk, intermediate-risk, and low-risk of aggressive disease. RESULTS: Most patients who had DTC with DM (66%) had a late-hit mutation in TERT, TP53, or PIK3CA. After propensity matching by age, tumor size, and sex, the high-risk molecular profile had strong association with DM (high-risk vs intermediate-risk: odds ratio, 25.1; 95% CI, 3.07-204.4; P < .001; high-risk vs low-risk: odds ratio, 122.5; 95% CI, 14.5-1038.4; P < .001). Overall, molecular risk categories were associated with DM risk, with a concordance index of 0.836 (95% CI, 0.759-0.913), which remained consistent after internal validation. Within the range of 5% to 10% of DM observed in DTC, the expected probability of DM would be 0.2% to 0.4% for the low-risk molecular profile, 4.7% to 9.4% for the intermediate-risk molecular profile, and 19.3% to 33.5% for the high-risk molecular profile. CONCLUSIONS: In this matched case-control study, genetic profiling using an available molecular assay provided accurate and robust risk stratification for DM in patients with DTC. The availability of preoperative prognostication may allow tailoring treatment for patients with DTC.
Asunto(s)
Adenocarcinoma , Neoplasias de la Tiroides , Adenocarcinoma/genética , Adenocarcinoma/patología , Estudios de Casos y Controles , Humanos , Mutación , Medición de Riesgo , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/patologíaRESUMEN
BACKGROUND: Computed tomography (CT) is commonly performed when evaluating trauma patients with up to 55% showing incidental findings. Current workflows to identify and inform patients are time-consuming and prone to error. Our objective was to automatically identify thyroid and adrenal lesions in radiology reports using deep learning. MATERIALS AND METHODS: All trauma patients who presented to an accredited Level 1 Trauma Center between January 2008 and January 2019 were included. Radiology reports of CT scans that included either a thyroid or adrenal gland were obtained. Preprocessing included word tokenization, removal of stop words, removal of punctuation, and replacement of misspellings. A word2vec model was trained using 1.4 million radiology reports. Both training and testing reports were selected at random, manually reviewed, and were considered the gold standard. True positive cases were defined as any lesions in the thyroid or adrenal gland, respectively. Training data was used to create models that would identify reports that contained either thyroid or adrenal lesions. Our primary outcomes were sensitivity and specificity of the models using predetermined thresholds on a separate testing dataset. RESULTS: A total of 51,771 reports were identified on 35,859 trauma patients. A total of 1,789 reports were annotated for training and 500 for testing. The thyroid model predictions resulted in a 90.0% sensitivity and 95.3% specificity. The adrenal model predictions resulted in a 92.3% sensitivity and a 91.1% specificity. A total of 240 reports were confirmed to have thyroid incidentals (mean age 69.1 yrs ± 18.9, 35% M) and 214 reports with adrenal incidentals (mean age 68.7 yrs ± 16.9, 50.5% M). CONCLUSIONS: Both the thyroid and adrenal models have excellent performance with sensitivities and specificities in the 90s. Our deep learning model has the potential to reduce administrative costs and improve the process of informing patients.
Asunto(s)
Neoplasias de las Glándulas Suprarrenales/diagnóstico por imagen , Reglas de Decisión Clínica , Aprendizaje Profundo , Hallazgos Incidentales , Neoplasias de la Tiroides/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Heridas y Lesiones/diagnóstico por imagen , Neoplasias de las Glándulas Suprarrenales/complicaciones , Adulto , Anciano , Algoritmos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Sensibilidad y Especificidad , Neoplasias de la Tiroides/complicaciones , Heridas y Lesiones/complicacionesRESUMEN
Virtual forms of communication have been integrated into academic surgery now more than ever. The COVID-19 pandemic accelerated its implementation in an effort to support social-distancing. Academic surgery is now learning valuable lessons from early experiences to optimally integrate this communication mode. The Society of Asian Academic Surgeons convened an expert panel during the society's fifth annual meeting that explores these lessons. Realms of virtual communication including meetings, networking, surgery department administration, social media, application processes, and advice for early or mid-career academic surgeons are explored. Virtual conferences pose a new challenge by removing the in-person component that is evident to be integral to networking, collaboration, and all aspects of academic socialization. Strategies such as creating virtual chat rooms, mentor-mentee virtual introductions, and deliberate interactions can enhance the experience. Virtual administrative meetings require special attention to preparation and strategies to insure engagement. Social media can be a valuable tool to integrate into academic careers but special attention needs to be made to utilize it deliberately and not to shy away from our individuality. The interview process can be enhanced when made virtual to give opportunities to those typically disadvantaged in the usual, in-person process.
Asunto(s)
COVID-19 , Congresos como Asunto , Medios de Comunicación Sociales , Cirujanos , Humanos , PandemiasRESUMEN
OBJECTIVE: FN present a management quandary as they are often benign but may also be aggressive TC. Consensus recommendations have historically advised thyroidectomy for definitive diagnosis. Although MT have robust benefit in hypothetical cost analyses, under current management guidelines a real-time study of their clinical utility in FN is awaited. We investigate if MT use for FN directs appropriate thyroidectomy for TC while triaging to surveillance nodules that are likely benign. METHODS: Data were analyzed for 389 consecutive patients managed from 11/14 to 9/19 for 405 FN, excluding oncocytic neoplasms. TC was defined as same-nodule histologic malignancy. When obtained, MT was performed using ThyroSeq (TS) v2 or 3. RESULTS: With a mean nodule size of 2.7â±â1.3âcm, MT was used in 89% and was positive in 39%. When MT was positive, thyroidectomy was more often utilized (91% v. MT- 27%; P < 0.001) and more likely for histologic TC (70% vs 16%, P < 0.001). With preoperative MT, all American Thyroid Association intermediate, high-risk, and medullary TC were positive whereas all MT- malignancies were low-risk. With TSv3, ultrasound surveillance was more likely for MT- FN (90% vs TSv2 65%, P < 0.001), and occurred for a total of 174 MT- FN. With mean follow-up of 24.6 months, 82% remained stable in size. CONCLUSIONS: MT use for FN increased the surgical yield of cancer by 4-fold, identified all potentially aggressive malignancies, and allowed apparently safe nonoperative surveillance for >80% of MT-negative patients. Thyroid nodule MT optimizes patient outcomes sufficiently to justify its incorporation into routine practice.
Asunto(s)
Técnicas de Diagnóstico Molecular , Nódulo Tiroideo/diagnóstico , Adulto , Anciano , Biopsia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Nódulo Tiroideo/patología , Nódulo Tiroideo/cirugía , TiroidectomíaRESUMEN
OBJECTIVE: The aim of this study was to develop evidence-based recommendations for safe, effective and appropriate thyroidectomy. BACKGROUND: Surgical management of thyroid disease has evolved considerably over several decades leading to variability in rendered care. Over 100,000 thyroid operations are performed annually in the United States. METHODS: The medical literature from January 1, 1985 to November 9, 2018 was reviewed by a panel of 19 experts in thyroid disorders representing multiple disciplines. The authors used the best available evidence to construct surgical management recommendations. Levels of evidence were determined using the American College of Physicians grading system, and management recommendations were discussed to consensus. Members of the American Association of Endocrine Surgeons reviewed and commented on preliminary drafts of the content. RESULTS: These clinical guidelines analyze the indications for thyroidectomy as well as its definitions, technique, morbidity, and outcomes. Specific topics include Pathogenesis and Epidemiology, Initial Evaluation, Imaging, Fine Needle Aspiration Biopsy Diagnosis, Molecular Testing, Indications, Extent and Outcomes of Surgery, Preoperative Care, Initial Thyroidectomy, Perioperative Tissue Diagnosis, Nodal Dissection, Concurrent Parathyroidectomy, Hyperthyroid Conditions, Goiter, Adjuncts and Approaches Laryngology Familial Thyroid Cancer, Postoperative Care and Complications, Cancer Management, and Reoperation. CONCLUSION: Evidence-based guidelines were created to assist clinicians in the optimal surgical management of thyroid disease.
Asunto(s)
Endocrinología/normas , Medicina Basada en la Evidencia/normas , Enfermedades de la Tiroides/cirugía , Tiroidectomía/normas , Adulto , Humanos , Estados UnidosRESUMEN
OBJECTIVE: To develop evidence-based recommendations for safe, effective, and appropriate thyroidectomy. BACKGROUND: Surgical management of thyroid disease has evolved considerably over several decades leading to variability in rendered care. Over 100,000 thyroid operations are performed annually in the US. METHODS: The medical literature from 1/1/1985 to 11/9/2018 was reviewed by a panel of 19 experts in thyroid disorders representing multiple disciplines. The authors used the best available evidence to construct surgical management recommendations. Levels of evidence were determined using the American College of Physicians grading system, and management recommendations were discussed to consensus. Members of the American Association of Endocrine Surgeons reviewed and commented on preliminary drafts of the content. RESULTS: These clinical guidelines analyze the indications for thyroidectomy as well as its definitions, technique, morbidity, and outcomes. Specific topics include Pathogenesis and Epidemiology, Initial Evaluation, Imaging, Fine Needle Aspiration Biopsy Diagnosis, Molecular Testing, Indications, Extent and Outcomes of Surgery, Preoperative Care, Initial Thyroidectomy, Perioperative Tissue Diagnosis, Nodal Dissection, Concurrent Parathyroidectomy, Hyperthyroid Conditions, Goiter, Adjuncts and Approaches to Thyroidectomy, Laryngology, Familial Thyroid Cancer, Postoperative Care and Complications, Cancer Management, and Reoperation. CONCLUSIONS: Evidence-based guidelines were created to assist clinicians in the optimal surgical management of thyroid disease.
Asunto(s)
Endocrinología/normas , Medicina Basada en la Evidencia/normas , Enfermedades de la Tiroides/cirugía , Tiroidectomía/normas , Adulto , Humanos , Estados UnidosRESUMEN
BACKGROUND: The addition of SPECT-CT to Tc-99 sestamibi has become a valuable tool for parathyroid localization in primary hyperparathyroidism (PHP). However, the enhanced sensitivity of this test can lead to unexpected and significant findings. We sought to identify the frequency and types of nonparathyroid detections by SPECT-CT. MATERIALS AND METHODS: With institutional approval, we reviewed all SPECT-CT studies performed for PHP between October 2012 and August 2018 for incidental nonparathyroid abnormalities. The electronic medical record was referenced to determine the type of lesion confirmed by additional evaluation. RESULTS: Among 2413 studies, 652 patients (27%) had 677 (28%) nonparathyroid findings. The most common were thyroid nodules (331/677, 49%), including 47 (6.9%) malignancies to date: 40 papillary thyroid cancers (11 microcarcinomas), five follicular thyroid cancers, one medullary carcinoma, and one noninvasive follicular thyroid neoplasm with papillary-like features. One hundred and seventy-seven patients had pulmonary nodules (26%), of whom nine were diagnosed with primary lung lesions (6 non-small-cell cancers, one small-cell cancer, one carcinoid, and one pulmonary sequestration). SPECT-CT revealed 14 patients (2.1%) with breast abnormalities, including three cancers. Nine patients (1.3%) demonstrated metastatic diseases within the lungs (4), bones (3), and mediastinum (2). One patient was diagnosed with follicular lymphoma. Two intracranial tumors were also identified, as well as dysplastic Barrett's esophagitis (1), hiatal hernia (20, 3%), and aortic aneurysm (13, 1.8%). In all, 72/677 (10.6%) PHP patients exhibited premalignant or malignant nonparathyroid SPECT-CT findings. CONCLUSIONS: In patients undergoing localization for PHP with Tc-99 sestamibi SPECT-CT, nonparathyroid findings are frequent (27%) and can lead to newly diagnosed malignant or premalignant lesions in at least 3% of patients to date.
Asunto(s)
Hiperparatiroidismo Primario/diagnóstico por imagen , Hallazgos Incidentales , Neoplasias Pulmonares/epidemiología , Neoplasias de la Tiroides/epidemiología , Tomografía Computarizada de Emisión de Fotón Único/métodos , Adulto , Femenino , Humanos , Neoplasias Pulmonares/diagnóstico , Masculino , Glándulas Paratiroides/diagnóstico por imagen , Radiofármacos , Sensibilidad y Especificidad , Tecnecio Tc 99m Sestamibi , Neoplasias de la Tiroides/diagnóstico , Tomografía Computarizada de Emisión de Fotón Único/estadística & datos numéricosRESUMEN
BACKGROUND: Approximately 30% of patients with apparent sporadic pheochromocytoma (Pheo) may later prove to have an inherited predisposition syndrome, most commonly Von Hippel-Lindau (VHL) disease. Our aim was to compare the clinical and biochemical features of Pheo in VHL to those in sporadic disease to identify differences that may be used to guide management and surveillance of Pheo in VHL patients. METHODS: Data of all patients who had adrenalectomy for histologic Pheo from 2000 to 2018 (QIIRB1749) were retrospectively reviewed. VHL patients were diagnosed by standard clinical criteria and/or genetic testing. Patients were classified as having sporadic Pheo (sPheo) if they had no family/personal history consistent with an associated genetic disorder and/or had negative testing for VHL, MAX, MEN1, NF1, RET and SDHAF2/B/C/D/A mutations. RESULTS: Of 175 patients, 38 (22%) had VHL and 137 (78%) had sPheo including 27 (20%) with negative genetic testing. Compared to sPheo, VHL Pheo patients were younger (mean 25.9 vs. 51.2 years, p < 0.001), less symptomatic (55% vs. 72%, p = 0.074), less hypertensive (46% vs. 64%, p = 0.043) and were more likely to have normal plasma metanephrines (85% vs. 25%, p < 0.001). VHL-related Pheos were smaller (median 2.8 cm vs. 4.4 cm, p < 0.001) but more often multifocal (>1 adrenal Pheo) (16% vs. 0%, p < 0.001). Recurrence >6 months from initial resection was common in VHL (40% vs. 0%, p < 0.001), median time to recurrence 15 years, (range 1-38 years). CONCLUSIONS: Compared to those with sporadic Pheo, patients with VHL are more likely to be young, asymptomatic and normotensive and to have small, multifocal, normetanephrine-secreting tumors. Because recurrence is common in VHL and arises up to 38 years later, continued surveillance is advised.
Asunto(s)
Neoplasias de las Glándulas Suprarrenales/genética , Feocromocitoma/genética , Enfermedad de von Hippel-Lindau/genética , Adolescente , Neoplasias de las Glándulas Suprarrenales/etiología , Adulto , Anciano , Niño , Preescolar , Femenino , Pruebas Genéticas , Humanos , Masculino , Persona de Mediana Edad , Feocromocitoma/etiología , Estudios Retrospectivos , Adulto Joven , Enfermedad de von Hippel-Lindau/complicacionesRESUMEN
BACKGROUND: Management of patients with bilateral adrenal masses and ACTH-independent Cushing's syndrome (AICS) is challenging, as bilateral adrenalectomy can lead to steroid dependence and lifelong risk of adrenal crisis. Adrenal venous sampling (AVS) has been previously reported to facilitate lateralization for guiding adrenalectomy. The aim of the current study was to investigate the utility of AVS using protocol from study by Young et al. in the management of patients with bilateral adrenal masses and AICS. METHODS AND DESIGN: A retrospective review of all patients with bilateral adrenal masses and AICS who underwent AVS from 2008 to 2016 was performed. AVS for cortisol and epinephrine was performed with dexamethasone suppression. The adrenal vein to peripheral vein cortisol ratios and side-to-side cortisol lateralization ratios were calculated. RESULTS: AVS was successful in 8 of 9 patients. All 8 patients had AVS results indicating bilateral cortisol hypersecretion. Six patients underwent adrenalectomy: 3 had unilateral adrenalectomy of the larger size mass, 2 had bilateral adrenalectomy (both sides >4 cm.) and 1 had stepwise bilateral adrenalectomy. Final pathology revealed macronodular adrenal hyperplasia in all 6 patients that underwent surgery. CONCLUSION: AVS was useful in excluding a unilateral adenoma as the source of AICS in this study of patients with bilateral adrenal masses and AICS. However, adrenal mass size influenced surgical decision making more than AVS results. More data are needed before AVS can be advocated as essential for management of patients with bilateral adrenal masses and AICS.
Asunto(s)
Neoplasias de las Glándulas Suprarrenales/cirugía , Adrenalectomía/métodos , Síndrome de Cushing/cirugía , Epinefrina/sangre , Hidrocortisona/sangre , Neoplasias de las Glándulas Suprarrenales/sangre , Glándulas Suprarrenales/irrigación sanguínea , Anciano , Síndrome de Cushing/sangre , Dexametasona/farmacología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , VenasRESUMEN
BACKGROUND: Molecular tests have clinical utility for thyroid nodules with indeterminate fine-needle aspiration (FNA) cytology, although their performance requires further improvement. This study evaluated the analytical performance of the newly created ThyroSeq v3 test. METHODS: ThyroSeq v3 is a DNA- and RNA-based next-generation sequencing assay that analyzes 112 genes for a variety of genetic alterations, including point mutations, insertions/deletions, gene fusions, copy number alterations, and abnormal gene expression, and it uses a genomic classifier (GC) to separate malignant lesions from benign lesions. It was validated in 238 tissue samples and 175 FNA samples with known surgical follow-up. Analytical performance studies were conducted. RESULTS: In the training tissue set of samples, ThyroSeq GC detected more than 100 genetic alterations, including BRAF, RAS, TERT, and DICER1 mutations, NTRK1/3, BRAF, and RET fusions, 22q loss, and gene expression alterations. GC cutoffs were established to distinguish cancer from benign nodules with 93.9% sensitivity, 89.4% specificity, and 92.1% accuracy. This correctly classified most papillary, follicular, and Hurthle cell lesions, medullary thyroid carcinomas, and parathyroid lesions. In the FNA validation set, the GC sensitivity was 98.0%, the specificity was 81.8%, and the accuracy was 90.9%. Analytical accuracy studies demonstrated a minimal required nucleic acid input of 2.5 ng, a 12% minimal acceptable tumor content, and reproducible test results under variable stress conditions. CONCLUSIONS: The ThyroSeq v3 GC analyzes 5 different classes of molecular alterations and provides high accuracy for detecting all common types of thyroid cancer and parathyroid lesions. The analytical sensitivity, specificity, and robustness of the test have been successfully validated and indicate its suitability for clinical use. Cancer 2018;124:1682-90. © 2018 American Cancer Society.
Asunto(s)
Biomarcadores de Tumor/genética , Neoplasias de las Paratiroides/diagnóstico , Neoplasias de la Tiroides/diagnóstico , Nódulo Tiroideo/diagnóstico , Biopsia con Aguja Fina , Análisis Mutacional de ADN/métodos , Diagnóstico Diferencial , Estudios de Seguimiento , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Humanos , Glándulas Paratiroides/patología , Neoplasias de las Paratiroides/genética , Neoplasias de las Paratiroides/patología , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Glándula Tiroides/patología , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/patología , Nódulo Tiroideo/genética , Nódulo Tiroideo/patologíaRESUMEN
PURPOSE OF REVIEW: Correct identification of malignancy in cytologically indeterminate thyroid nodules is a diagnostic challenge, leading to potentially unnecessary surgery in patients for whom final histology is benign. Similarly, many patients with differentiated thyroid cancer (DTC) undergo aggressive surgical management of tumors, which may ultimately have low-risk histologic features. Use of molecular testing strategies can aid in both the diagnosis of indeterminate thyroid nodules and preoperative risk stratification of DTC. RECENT FINDINGS: Validation studies of both the Afirma Gene Expression Classifier and Thyroseq Next-Generation Sequencing panel are ongoing. Both tests can be used to help rule out malignancy in indeterminate thyroid nodules. Recent additions to available molecular testing for indeterminate thyroid nodules include the Rosetta microRNA classifier and the augmentation of the ThyGenX gene panel with a microRNA reflex test (ThyraMIR). Mutational analysis of DTC shows that mutation in TERT alone, and in combination with other mutations, portends advanced disease. SUMMARY: Currently available molecular testing modalities are useful for ruling out malignancy in indeterminate thyroid nodules; however, longer-term follow-up studies are needed to confirm that test-negative nodules are truly benign. Analysis of specific gene mutations helps identify aggressive disease to guide prognostication and management, but further study is needed.
Asunto(s)
Neoplasias de la Tiroides/diagnóstico , Nódulo Tiroideo/diagnóstico , Diferenciación Celular/genética , Diagnóstico Diferencial , Humanos , Técnicas de Diagnóstico Molecular/métodos , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/patología , Nódulo Tiroideo/genética , Nódulo Tiroideo/patologíaRESUMEN
INTRODUCTION: In primary hyperparathyroidism (PHPT), parathyroid ectopia is seen in up to 22% leading to more difficult surgery. We aimed to determine the rate and characteristics of retropharyngeal (RP) parathyroid glands. METHODS: A prospective database was queried for patients with sporadic PHPT who had surgery from 1997 to 2016. The data of RP patients were compared to those who had surgery for sporadic PHPT over the same time period with hyperfunctioning parathyroids in anatomically normal positions (N). RESULTS: RP glands occurred in 47/3006 (1.6%) patients and were more common at reoperative than initial surgery (5.5 vs 1.4%, p < 0.01). RP patients had prior failed surgery more often than N patients (17 vs 3.1%, p < 0.01). Preoperative calcium levels (p = 0.06), PTH levels (p = 0.15), and mean gland weights (p = 0.07) were similar among groups. For RP glands, ultrasound imaging was negative in all but one patient, while 99mTc-sestamibi accurately indicated a posterior midline position in only 13/47 (28%) and was negative in 21%. All RP glands were anatomically superior. RP patients more often required > 1 post-resection intraoperative PTH level (36 vs 21%, p = 0.02). Failure due to persistent PHPT was more likely in RP patients (4.7 vs 2.1%, p = 0.2). CONCLUSION: In PHPT, hyperfunctioning RP glands are seen in 1.6% of cases and often associated with initial failure (17%). At reoperation, RP ectopia is 4X more common. RP glands are associated with a high rate of negative imaging, but imaging results suggestive of a midline abnormality can guide exploration. The RP space should be evaluated prior to ending an otherwise unfruitful surgery.
Asunto(s)
Hiperparatiroidismo Primario/patología , Hiperparatiroidismo Primario/cirugía , Glándulas Paratiroides/anatomía & histología , Paratiroidectomía , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Glándulas Paratiroides/diagnóstico por imagen , Estudios Prospectivos , UltrasonografíaRESUMEN
BACKGROUND: Parathyroid glands can mimic thyroid follicular lesions on fine-needle aspiration (FNA) cytology and can lead to unnecessary or incorrect surgery. Newer molecular panel tests using next-generation sequencing (NGS) include analysis of cell type-specific gene expression profiles such as parathyroid. The study aim is to determine the frequency and clinical implications of parathyroid tissue identification by molecular testing in cytologically indeterminate "thyroid" lesions. METHODS: Molecular analysis of indeterminate thyroid FNA specimens is obtained routinely and relies on amplification-based NGS inclusive of PTH-specific expression profiles. For this study, we retrospectively examined the clinical data and management of patients with molecular results positive for PTH expression from May 2014 until May 2016. RESULTS: Among 4765 consecutive patients with indeterminate cytology for a presumed thyroid nodule, NGS instead indicated a parathyroid lesion in 20 patients (0.42%). The clinical data of 15 patients were available, and the subsequent clinical management was altered in 93% (14/15 patients), including five (33%) eucalcemic patients who could avoid unnecessary surgery. Primary hyperparathyroidism was not suspected in seven patients until the molecular analysis results, and primary hyperparathyroidism was diagnosed in one (14%). During parathyroid exploration, most patients (6/8, 75%) required concurrent thyroidectomy or lobectomy, but thyroid preservation was still possible in two patients. A parathyroid gland was histologically confirmed in 89%. CONCLUSIONS: In 0.42% of patients with indeterminate cytology results, next-generation molecular results will indicate the presence of a parathyroid lesion. When this occurs, it is accurate and can robustly impact clinical management (93%).
Asunto(s)
Análisis Mutacional de ADN , Hallazgos Incidentales , Enfermedades de las Paratiroides/diagnóstico , Glándulas Paratiroides/patología , Nódulo Tiroideo/patología , Adulto , Anciano , Biopsia con Aguja Fina/métodos , Análisis Mutacional de ADN/métodos , Femenino , Humanos , Hiperparatiroidismo Primario/cirugía , Masculino , Persona de Mediana Edad , Enfermedades de las Paratiroides/patología , Periodo Preoperatorio , Estudios Retrospectivos , Neoplasias de la Tiroides/cirugía , Nódulo Tiroideo/cirugía , Tiroidectomía , Procedimientos InnecesariosRESUMEN
BACKGROUND AND PURPOSE: Factors associated with malignancy in patients with pheochromocytoma (adrenal tumors, Pheo) and paraganglioma (extra-adrenal, PGL) are not well-defined and all patients require lifelong surveillance. The primary aim of our study was to determine genetic and clinical variables associated with malignancy in patients with Pheo/PGL. METHODS: Single institution retrospective review was performed of all patients who underwent surgery (1/95-1/15) for Pheo/PGL. Malignancy was defined as histology-confirmed distant metastasis, lymph nodal involvement, or tumor bed recurrence. RESULTS: A total of 157 Pheo/PGL patients (44 malignant, 113 benign) with mean follow-up of 87 months were included. Compared with patients with benign Pheo/PGL, patients with malignant Pheo/PGL were younger (median 42 vs 50 years, p = 0.014), had larger tumors (median 6.5 vs 4 cm, p < 0.001) and had PGL (63.6 vs 4.4%, p < 0.001). Genetic testing was performed in 60 patients and was positive in 38 (63%). Although positive genetic results were equally likely in malignant vs benign Pheo/PGL (76 vs 54%, p = 0.1), all 11 patients with germline SDHB mutations had malignant disease. In multivariable analysis, younger age, larger tumor size, and PGL were associated with malignancy (p < 0.05). Pheo patients with negative genetic testing and negative family history who developed metachronous metastases all had primary tumors ≥4 cm in size. CONCLUSIONS: Patients who are young, have larger tumors, positive genetic testing (especially SDHB) or have PGL require long-term follow-up. Patients with negative genetic testing or family history and Pheo <4 cm have a lower risk of malignancy, and de-escalated long-term surveillance may be appropriate follow-up.
Asunto(s)
Neoplasias de las Glándulas Suprarrenales/secundario , Mutación de Línea Germinal , Recurrencia Local de Neoplasia/patología , Paraganglioma/patología , Feocromocitoma/patología , Succinato Deshidrogenasa/genética , Adolescente , Neoplasias de las Glándulas Suprarrenales/genética , Adulto , Anciano , Niño , Femenino , Estudios de Seguimiento , Pruebas Genéticas , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Recurrencia Local de Neoplasia/genética , Paraganglioma/genética , Feocromocitoma/genética , Pronóstico , Estudios Retrospectivos , Adulto JovenAsunto(s)
Cirujanos , Enfermedades de la Tiroides , Adulto , Humanos , Enfermedades de la Tiroides/cirugía , Tiroidectomía , Estados UnidosRESUMEN
OBJECTIVES: To correlate thyroid cancer genotype with histology and outcomes. BACKGROUND: The prognostic significance of molecular signature in thyroid cancer (TC) is undefined but can potentially change surgical management. METHODS: We reviewed a consecutive series of 1510 patients who had initial thyroidectomy for TC with routine testing for BRAF, RAS, RET/PTC, and PAX8/PPARG alterations. Histologic metastatic or recurrent TC was tracked for 6 or more months after oncologic thyroidectomy. RESULTS: Papillary thyroid cancer (PTC) was diagnosed in 97% of patients and poorly differentiated/anaplastic TC in 1.1%. Genetic alterations were detected in 1039 (70%); the most common mutations were BRAFV600E (644/1039, 62%), and RAS isoforms (323/1039, 31%). BRAFV600E-positive PTC was often conventional or tall cell variant (58%), with frequent extrathyroidal extension (51%) and lymph node metastasis (46%). Conversely, RAS-positive PTC was commonly follicular variant (87%), with infrequent extrathyroidal extension (4.6%) and lymph node metastasis (5.6%). BRAFV600E and RET/PTC-positive PTCs were histologically similar. Analogously, RAS and PAX8/PPARG-positive PTCs were histologically similar. Compared with RAS or PAX8/PPARG-positive TCs, BRAFV600E or RET/PTC-positive TCs were more often associated with stage III/IV disease (40% vs 15%, P < 0.001) and recurrence (10% vs 0.7%, P < 0.001; mean follow-up 33 ± 21 mo). Distant metastasis was highest in patients with RET/PTC-positive TC (10.8%, P = 0.02). CONCLUSIONS: In this large study of prospective mutation testing in unselected patients with TC, molecular signature was associated with distinctive phenotypes including cancers, with higher risks of both distant metastasis and early recurrence. Preoperative genotype provides valuable prognostic data to appropriately inform surgery.
Asunto(s)
Carcinoma/genética , Carcinoma/mortalidad , Regulación Neoplásica de la Expresión Génica , Proteínas Proto-Oncogénicas/genética , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/mortalidad , Adulto , Anciano , Carcinoma/patología , Carcinoma/cirugía , Carcinoma Papilar , Bases de Datos Factuales , Supervivencia sin Enfermedad , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Mutación , Invasividad Neoplásica , Estadificación de Neoplasias , Factor de Transcripción PAX8 , Factores de Transcripción Paired Box/genética , Fenotipo , Valor Predictivo de las Pruebas , Pronóstico , Proteínas Proto-Oncogénicas B-raf/genética , Proteínas Proto-Oncogénicas c-ret/genética , Estudios Retrospectivos , Análisis de Supervivencia , Cáncer Papilar Tiroideo , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/cirugía , Tiroidectomía/métodos , Tiroidectomía/mortalidad , Resultado del TratamientoRESUMEN
INTRODUCTION: In adrenal tumors, size ≥ 4 cm has been an indication for adrenalectomy due to concern for malignancy. We compared mass size to imaging features (ImF) for accuracy in diagnosing adrenal malignancy. METHODS: Data were retrieved for 112 consecutive patients who had adrenalectomy from January 2011 to August 2014. ImF was classified as nonbenign if HU > 10 on unenhanced CT scan or if loss of signal on out-of-phase imaging was absent on chemical-shift MRI. Indications for resection included hormonal hypersecretion, nonbenign ImF, and/or size ≥ 4 cm. RESULTS: Of 113 resected adrenals, 37 % were functional. Histologic malignancy occurred in 18 % (20/113) and included 3 adrenocortical carcinomas (ACC), 1 epithelioid liposarcoma, 1 lymphoma, 1 malignant nerve sheath tumor, and 14 adrenal metastases. Patients with malignancies were older (mean age, 60 ± 13 vs. 51 ± 14 years, p = 0.01). Malignant tumors were larger on preoperative imaging (mean 5.3 ± 3.2 vs. 3.9 ± 2.4 cm, p = 0.03). All 20 malignant masses had nonbenign ImF. In predicting malignancy, the sensitivity, specificity, NPV, and PPV of nonbenign ImF was 100, 57, 100, and 33 %, respectively. Size ≥ 4 cm was less predictive with sensitivity, specificity, NPV, and PPV of 55, 61, 86, and 23 %, respectively. If size ≥ 4 cm had been used as the sole criterion for surgery, 45 % of malignancies (9/20) would have been missed including 8 metastases and an ACC. CONCLUSIONS: In resected adrenal tumors, the presence of nonbenign ImF is more sensitive for malignancy than mass size (100 vs. 55 %) with equivalent specificity. Regardless of mass size, adrenalectomy should be strongly considered when non-benign ImF are present.
Asunto(s)
Neoplasias de las Glándulas Suprarrenales/patología , Adrenalectomía , Imagen por Resonancia Magnética/métodos , Tomografía Computarizada por Rayos X/métodos , Carga Tumoral , Adolescente , Neoplasias de las Glándulas Suprarrenales/clasificación , Neoplasias de las Glándulas Suprarrenales/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Adulto JovenRESUMEN
Molecular markers including gene expression profiles, somatic gene alterations, and circulating peripheral markers have augmented diagnostic, prognostic, and therapeutic options for thyroid cancer patients.