RESUMO
Adrenocortical carcinoma (ACC) is a rare malignancy whose risk factors are unclear. We explored the association of ACC risk with exposure to selected environmental factors, with a focus on cigarette smoking. We conducted a hospital-based case-control study at The University of Texas MD Anderson Cancer Center. Cases (n = 432) patients with ACC treated at MD Anderson, and controls (n = 1,204) were healthy and genetically unrelated spouses of patients at MD Anderson who had cancers not associated with smoking. Information on the subjects' demographic features and selected risk factors was collected using a structured, validated questionnaire and medical records review. Unconditional logistic regression was used to calculate adjusted odds ratios (AORs) via the maximum-likelihood method. Cases had a younger mean (± standard deviation) age than did controls (47.0 ± 0.7 and 60.0 ± 0.3 years, respectively), and the majority of cases were female (60.6%) and non-Hispanic white (82.4%). We found a markedly increased risk of ACC among male cigarette smokers, with an AOR = 1.8 (95% confidence interval [CI] =1.2-2.9), but not among female smokers (AOR = 1.1, 95% CI = 0.7-1.6). Family history of cancer was associated with increased risk of ACC (AOR = 2.8, 95% CI 1.9-4.3) and in both men and women, whereas alcohol consumption was associated with reduced risk in men (AOR = 0.2, 95% CI = 0.1-0.3) but not women (AOR = 0.7, 95% CI = 0.5-1.1). Understanding these risk factors and their underlying mechanisms may help prevent ACC in susceptible individuals and eventually identify new therapeutic options for ACC.
Assuntos
Carcinoma Adrenocortical/epidemiologia , Neoplasias do Córtex Suprarrenal/epidemiologia , Neoplasias do Córtex Suprarrenal/etiologia , Carcinoma Adrenocortical/etiologia , Idoso , Estudos de Casos e Controles , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Medição de Risco , Fatores de RiscoRESUMO
BACKGROUND: The American Joint Committee on Cancer 8th edition staging manual for adrenocortical carcinoma (ACC) redefines T stage to include large vessel invasion (T4, previously undescribed) and restricts stage IV to those with distant metastases. We evaluated the prognostic power of the 8th edition. METHODS: Patients with ACC treated between January 1, 2000, and December 31, 2015, were identified. Overall survival (OS) was compared using Kaplan-Meier and Cox proportional hazard models. RESULTS: Of 290 patients evaluated, the change in T stage nomenclature impacted 13 (4.5%) who were previously categorized as T3; 61 had large vessel involvement but were already T4 based on invasion of adjacent organs. The restriction of stage IV to patients with distant metastases downstaged 41 (14.1%; T4N0M0 or T3-4N1M0) to stage III. In the 7th edition, the hazard ratio (HR) for death was similar between patients with stage II and III disease, with 5-year OS 66.7%, 54.4%, 57.2%, and 14.0% (stages I, II, III, and IV, respectively). In the 8th edition, stages I and II remain unchanged, with 5-year OS for stage III and IV 44.1% and 9.2%, respectively. The c-index for the 7th and 8th editions was similar (83.4 and 82.7, respectively). CONCLUSIONS: While 8th edition changes impact a relatively small proportion of ACC patients, they represent progress toward a common staging system that accurately reflects prognosis. In the 8th edition, the inclusion of patients with T4 tumors or nodal disease as stage III rather than IV results in improved stratification between stages II and III.
Assuntos
Neoplasias do Córtex Suprarrenal/patologia , Carcinoma Adrenocortical/patologia , Adolescente , Neoplasias do Córtex Suprarrenal/mortalidade , Carcinoma Adrenocortical/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estados Unidos , Adulto JovemRESUMO
PURPOSE: The aims of the study were to assess the typical and atypical radiologic features of pathologically proven adrenal adenomas and to determine the relationship between the radiologic and histopathologic classification. METHODS: We retrospectively studied 156 pathologically proven adrenal adenomas in 154 patients from our institutional databases who have computed tomography (CT) and/or magnetic resonance imaging (MRI) examinations before intervention. We determined the histopathologic diagnosis (typical or atypical) using Weiss scoring and classified the adenomas radiologically into typical, atypical, or indeterminate based on lesion size, precontrast CT attenuation, absolute percentage washout, calcification, and necrosis. The κ statistic was used to assess the agreement between radiologists. The Fisher exact test was used to compare the radiologic and pathological classifications. RESULTS: In consensus, there were 83 typical, 42 atypical, and 31 indeterminate adrenal lesions. Logistic regression model showed that radiologically atypical adenoma was significantly associated with larger size, lobulated shape, higher unenhanced CT attenuation, heterogeneous appearance, nonfunctioning status, absolute percentage washout of less than 60%, and a signal intensity index of less than 16.5%.Pathologically, 147 adenomas were pathologically typical (Weiss 0), and 9 adenomas were pathologically atypical (Weiss 1-2). Radiologically, there was substantial agreement between both readers, with Cohen κ at 0.71. Approximately 98% of radiologically typical adenomas were pathologically typical. Only 17% of radiologically atypical adenomas were pathologically atypical. All radiologically indeterminate adenomas were pathologically typical. However, some of the radiologically indeterminate and typical adenomas still had an atypical component on pathologic analysis, such as necrosis, nuclear atypia, or oncocytic features. CONCLUSIONS: Radiologically atypical lesion was significantly associated with larger size and higher unenhanced CT attenuation. Approximately 27% of the cases demonstrated atypical features on imaging. Most radiologically atypical adrenal adenomas are pathologically typical.
Assuntos
Neoplasias das Glândulas Suprarrenais/diagnóstico por imagem , Neoplasias das Glândulas Suprarrenais/patologia , Cuidados Pré-Operatórios/métodos , Tomografia Computadorizada por Raios X/métodos , Adenoma/diagnóstico por imagem , Adenoma/patologia , Adolescente , Neoplasias das Glândulas Suprarrenais/cirurgia , Glândulas Suprarrenais/diagnóstico por imagem , Glândulas Suprarrenais/patologia , Glândulas Suprarrenais/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemRESUMO
OBJECTIVE: To determine whether primary tumor resection in patients with metastatic pheochromocytoma or paraganglioma (PPG) is associated with longer overall survival (OS). BACKGROUND: Patients with metastatic PPG have poor survival outcomes. The impact of surgical resection of the primary tumor on OS is not known. METHODS: We retrospectively studied patients with metastatic PPG treated at the University of Texas, MD Anderson Cancer Center from January 2000 through January 2015. Kaplan-Meier analysis with log-rank tests was used to compare OS among patients undergoing primary tumor resection and patients not treated surgically. Propensity score method was applied to adjust for selection bias using demographic, clinical, biochemical, genetic, imaging, and pathologic information. RESULTS: A total of 113 patients with metastatic PPG were identified. Eighty-nine (79%) patients had surgery and 24 (21%) patients did not. Median OS was longer in patients who had surgery than in patients who did not [148 months, 95% confidence interval (CI) 112.8-183.2 months vs 36 months, 95% CI 27.2-44.8 months; P < 0.001].Fifty-three (46%) patients had synchronous metastases; of these patients, those who had surgery had longer OS than those who did not (85 months, 95% CI 64.5-105.4 months vs 36 months, 95% CI 29.7-42.3 months; P < 0.001). Patients who had surgery had a similar ECOG performance status to the ones who did not (P = 0.1798, two sample t test; P = 0.2449, Wilcoxon rank sum test). Univariate and propensity score analysis confirmed that patients treated with surgery had longer OS than those not treated surgically irrespective of age, race, primary tumor size and location, number of metastatic sites, and genetic background (log-rank P < 0.001).In patients with hormonally active tumors (70.8%), the symptoms of catecholamine excess improved after surgery. However, the tumor burden was a more important determinant of OS than hormonal secretion. CONCLUSIONS: Primary tumor resection in patients with metastatic PPG appeared to be associated with improved OS. In patients with hormonally active tumors, surgical resection led to better blood pressure control.
Assuntos
Neoplasias das Glândulas Suprarrenais/cirurgia , Paraganglioma/cirurgia , Adolescente , Neoplasias das Glândulas Suprarrenais/mortalidade , Neoplasias das Glândulas Suprarrenais/patologia , Adulto , Idoso , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Paraganglioma/mortalidade , Paraganglioma/patologia , Feocromocitoma/mortalidade , Feocromocitoma/patologia , Feocromocitoma/cirurgia , Qualidade de Vida , Estudos Retrospectivos , Análise de Sobrevida , Adulto JovemRESUMO
BACKGROUND: The objective of this study was to evaluate the clinical benefits of systemic chemotherapy for patients with metastatic pheochromocytomas or sympathetic paragangliomas by assessing reductions in tumor size and blood pressure and improvements in overall survival (OS). METHODS: The authors retrospectively reviewed the medical records of patients with metastatic pheochromocytomas-sympathetic paragangliomas who had received chemotherapy at The University of Texas MD Anderson Cancer Center. RESULTS: Clinical benefit and OS were assessed. Of 54 patients who received chemotherapy, 52 patients were evaluable for response. Seventeen patients (33%) experienced a response, which was defined as decreased or normalized blood pressure/decreased number and dosage of antihypertensive medications and/or reduced tumor size after the first chemotherapy regimen. The median OS was 6.4 years (95% confidence interval [CI], 5.2-16.4 years) for responders and 3.7 years (95% CI, 3.0-7.5 years) for nonresponders. Among the patients who had synchronous metastatic disease, a positive response at 1 year after the start of chemotherapy was associated with a trend toward longer OS (log-rank test; P = .095). In a multivariate Cox proportional hazards model, the effect of response to chemotherapy on OS was significant (hazard ratio, 0.22; 95% CI, interval: 0.05-1.0; P = .05). All responders had received dacarbazine and cyclophosphamide. Vincristine was included for 14 responders, and doxorubicin was included for 12 responders. The clinical factors that predicted response to chemotherapy could not be identified. CONCLUSIONS: The current results indicted that chemotherapy may decrease tumor size and facilitate blood pressure control in approximately 33% of patients with metastatic pheochromocytoma-sympathetic paraganglioma. These patients exhibited longer survival.
Assuntos
Neoplasias das Glândulas Suprarrenais/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Paraganglioma Extrassuprarrenal/tratamento farmacológico , Feocromocitoma/tratamento farmacológico , Neoplasias das Glândulas Suprarrenais/mortalidade , Neoplasias das Glândulas Suprarrenais/patologia , Neoplasias das Glândulas Suprarrenais/fisiopatologia , Adulto , Idoso de 80 Anos ou mais , Pressão Sanguínea , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Paraganglioma Extrassuprarrenal/mortalidade , Paraganglioma Extrassuprarrenal/patologia , Paraganglioma Extrassuprarrenal/fisiopatologia , Feocromocitoma/mortalidade , Feocromocitoma/patologia , Feocromocitoma/fisiopatologiaRESUMO
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.
Assuntos
Síndrome de ACTH Ectópico , Síndrome de Cushing , Hiperglicemia , Tumores Neuroendócrinos , Síndrome de ACTH Ectópico/complicações , Síndrome de ACTH Ectópico/diagnóstico , Adrenalectomia/efeitos adversos , Hormônio Adrenocorticotrópico , Síndrome de Cushing/diagnóstico , Síndrome de Cushing/etiologia , Síndrome de Cushing/cirurgia , Humanos , Hiperglicemia/complicações , Tumores Neuroendócrinos/complicações , Tumores Neuroendócrinos/cirurgia , Estudos RetrospectivosRESUMO
PURPOSE OF REVIEW: Paraneoplastic syndromes occur commonly in patients with lung cancer, especially cancers of neuroendocrine origin. The syndromes can be the first clinical manifestation of malignant disease or a harbinger of cancer recurrence. To update the knowledge that would facilitate the care of lung cancer patients with paraneoplastic syndromes, this review focuses on the epidemiology, pathogenesis, clinical features, and current management of the more common and clinically relevant syndromes. RECENT FINDINGS: Certain combinations of clinical signs and symptoms (endocrine, neurologic, immunologic, dermatologic, metabolic, constitutional, and hematologic) are associated with lung carcinoma as a manifestation of the secretion of cytokines and hormones by these cells or as an associated immunologic response. These syndromes can be categorized by common causative mechanisms: hormonal syndromes, autoimmune syndromes, and other syndromes of less clear cause. Recent advances in medical technology have allowed better understanding of these syndromes and the development of novel diagnostic and therapeutic tools. SUMMARY: Increased awareness of paraneoplastic syndromes associated with lung cancer should lead to the earlier recognition and diagnosis of malignancies, thereby improving the overall prognosis of patients and alleviating associated comorbidities. Despite the recent advances in recognizing and treating paraneoplastic syndromes, many questions remain to be answered.
Assuntos
Neoplasias Pulmonares/complicações , Síndromes Paraneoplásicas/etiologia , HumanosRESUMO
GOAL: To evaluate the ability of radiomic feature extraction and a machine learning algorithm to differentiate between benign and malignant indeterminate adrenal lesions on contrast-enhanced computed tomography (CT) studies. BACKGROUND: Adrenal "incidentalomas" are adrenal lesions that are accidentally discovered during workup not related to the adrenal glands; they have an incidence as high as 5%. Small adrenal incidentalomas (< 4 cm) with high attenuation values on pre-contrast CT(> 10 HU) need further evaluation to calculate the absolute percentage of washout (APW). If the APW is < 60%, these lesions are considered non-adenomas and commonly classified as indeterminate adrenal lesions. Further workup for indeterminate lesions includes more complicated and expensive radiological studies or invasive procedures like biopsy or surgical resection. METHODS: We searched our institutional database for indeterminate adrenal lesions with the following characteristics: < 4 cm, pre-attenuation value > 10 HU, and APW < 60%. Exclusion criteria included pheochromocytoma and no histopathological examination. CT images were converted to Nifti format, and adrenal tumors were segmented using Amira software. Radiomic features from the adrenal mask were extracted using PyRadiomics software after removing redundant features (highly pairwise correlated features and low-variance features) using recursive feature extraction to select the final discriminative set of features. Lastly, the final features were used to build a binary classification model using a random forest algorithm, which was validated and tested using leave-one-out cross-validation, confusion matrix, and receiver operating characteristic curve. RESULTS: We found 40 indeterminate adrenal lesions (21 benign and 19 malignant). Feature extraction resulted in 3947 features, which reduced down to 62 features after removing redundancies. Recursive feature elimination resulted in the following top 4 discriminative features: gray-level size zone matrix-derived size zone non-uniformity from pre-contrast and delayed phases, gray-level dependency matrix-derived large dependence high gray-level emphasis from venous-phase, and gray-level co-occurrence matrix-derived cluster shade from delayed-phase. A binary classification model with leave-one-out cross-validation showed AUC = 0.85, sensitivity = 84.2%, and specificity = 71.4%. CONCLUSION: Machine learning and radiomic features extraction can differentiate between benign and malignant indeterminate adrenal tumors and can be used to direct further workup with high sensitivity and specificity.
Assuntos
Neoplasias das Glândulas Suprarrenais , Neoplasias das Glândulas Suprarrenais/diagnóstico por imagem , Algoritmos , Humanos , Aprendizado de Máquina , Estudos Retrospectivos , Tomografia Computadorizada por Raios XRESUMO
Most adrenal incidentalomas are non-functioning adenomas that require no treatment. The presence of a myelolipomatous component of adrenal incidentalomas is a rare, but well-known occurrence in both hyperplastic and neoplastic lesions of the adrenal cortex. Although the improvements in abdominal imaging have increased identification of myelolipomatous adrenal cortical adenomas radiologically, due to the rarity of this lesion, the clinical pathological features of these lesions are unclear and can sometimes cause diagnostic difficulty. Eleven patients had surgeries at The University of Texas MD Anderson Cancer Center. Four additional cases were provided from an external collaborator. Of the 15 cases, there were 5 male and 10 female patients, with a median age of 52 years (mean 54 years, range 28-84 years). Clinical presentation included adrenal incidentaloma (n = 9), Cushing syndrome (n = 4, including 1 as a part of Carney complex), and subclinical Cushing syndrome (n = 2, including 1 with bilateral macronodular adrenal hyperplasia). In this study, we present the clinicopathologic features of fifteen myelolipomatous adrenal adenomas, the largest series published thus far.
Assuntos
Adenoma/diagnóstico por imagem , Neoplasias das Glândulas Suprarrenais/diagnóstico por imagem , Síndrome de Cushing/diagnóstico por imagem , Achados Incidentais , Adenoma/complicações , Adenoma/patologia , Neoplasias das Glândulas Suprarrenais/complicações , Neoplasias das Glândulas Suprarrenais/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Síndrome de Cushing/etiologia , Síndrome de Cushing/patologia , Feminino , Humanos , Hiperplasia/complicações , Hiperplasia/diagnóstico por imagem , Hiperplasia/patologia , Masculino , Pessoa de Meia-IdadeRESUMO
The evaluation and management of adrenal disease is a complex endeavor that relies on an expert knowledge of human physiology and anatomy. Careful and proper patient assessment mandates a balanced approach which marries the disciplines of endocrinology, surgery, and radiology. Any of these three specialties may be on the front line in performing the initial workup when an adrenal neoplasm is discovered. With an ever-increasing volume of cross-sectional imaging, be it CT, MRI, or PET, large numbers of adrenal incidentalomas are being discovered. A close collaboration amongst specialties should strive to streamline the initial evaluation and minimize unnecessary testing and treatment.
Assuntos
Neoplasias das Glândulas Suprarrenais/diagnóstico por imagem , Neoplasias das Glândulas Suprarrenais/terapia , Gerenciamento Clínico , Diagnóstico Diferencial , Endocrinologistas , Endocrinologia , Humanos , Achados IncidentaisRESUMO
Introduction: Pheochromocytomas and sympathetic paragangliomas (PPGL) are neuroendocrine catecholamine-secreting tumors that are usually localized. Metastatic disease is rare and systemic treatment consists of conventional chemotherapy and high-specific-activity iodine-131-MIBG which was approved by the FDA in 2018. Although chemotherapy combinations still have value in specific settings, the debilitating side effects of treatment with only modest benefit have limited their use. With the introduction of a new generation of targeted therapy and immunotherapy patients with metastatic PPGL may have improved therapeutic options. Areas Covered: The current paper presents a case of a patient with metastatic PPGL who received multiple lines of systemic treatment. Despite progression on previous single agent cabozantinib and single agent pembrolizumab on separate clinical trials, the patient has exhibited a major response to the combination of cabozantinib and nivolumab for the past 22 months. In addition, we will review the available therapies for metastatic PPGL and discuss novel agents under clinical development. Conclusion: Newer targeted therapies and immunotherapy options are under clinical development with promising results for patients with PPGL.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Paraganglioma/tratamento farmacológico , Adulto , Anilidas/administração & dosagem , Humanos , Masculino , Nivolumabe/administração & dosagem , Paraganglioma/secundário , Prognóstico , Piridinas/administração & dosagemRESUMO
Adrenocortical carcinoma (ACC) is a rare tumor with a poor prognosis. Most tumors are either metastatic or locally invasive at the time of diagnosis. Differentiation between ACC and other adrenal masses depends on clinical, biochemical, and imaging factors. This review will discuss the genetics, pathological, and imaging feature of ACC.
Assuntos
Neoplasias do Córtex Suprarrenal/diagnóstico por imagem , Neoplasias do Córtex Suprarrenal/genética , Carcinoma Adrenocortical/diagnóstico por imagem , Carcinoma Adrenocortical/genética , Genômica , Neoplasias do Córtex Suprarrenal/patologia , Carcinoma Adrenocortical/patologia , Diagnóstico Diferencial , Humanos , Estadiamento de Neoplasias , PrognósticoRESUMO
BACKGROUND: In the face of the COVID-19 pandemic, cancer care has had to adapt rapidly given the Centers for Disease Control and Prevention and the American College of Surgeons (ACS) issuing recommendations to postpone nonurgent surgeries. METHODS: An institutional multidisciplinary group of Head and Neck Surgical Oncology, Surgical Endocrinology, and Medical Endocrinology devised Surgical Triaging Guidelines for Endocrine Surgery during COVID-19, aligned with phases of care published by the ACS. RESULTS: Phases of care with examples of corresponding endocrine cases are outlined. Most cases can be safely postponed with active surveillance, including most differentiated and medullary thyroid cancers. During the most acute phase, all endocrine surgeries are deferred, except thyroid tumors requiring acute airway management. CONCLUSIONS: These guidelines provide context for endocrine surgery within the spectrum of surgical oncology, with the goal of optimal individualized multidisciplinary patient care and the expectation of significant resource diversion to care for patients with COVID-19.
Assuntos
Betacoronavirus , Infecções por Coronavirus/epidemiologia , Doenças do Sistema Endócrino/cirurgia , Seleção de Pacientes , Pneumonia Viral/epidemiologia , Triagem , Algoritmos , COVID-19 , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/transmissão , Doenças do Sistema Endócrino/patologia , Humanos , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Pneumonia Viral/transmissão , Guias de Prática Clínica como Assunto , SARS-CoV-2RESUMO
PURPOSE: Large adrenal masses pose a diagnostic dilemma. The purpose of this study was twofold: first, to assess the degree of interobserver agreement in evaluating the morphology of pathologically proven adrenal adenomas and adrenocortical carcinomas larger than 4 cm in diameter; and second, to identify morphologic characteristics that correlated with the pathologic diagnosis. MATERIALS AND METHODS: For this blinded, retrospective study, we collected cases of 25 adrenal adenomas and 33 adrenocortical carcinomas measuring larger than 4 cm. Two radiologists evaluated morphologic characteristics of the lesions on CT. Interobserver agreement was evaluated using kappa statistics, and the correlation of imaging characteristics with the diagnosis was evaluated using a logistic regression model. RESULTS: We found the highest interobserver agreement in the assessment of precontrast attenuation (Κ = 0.81) as well as substantial agreement in determining the shape and the presence of calcifications (Κ = 0.69 and 0.74, respectively). Readers agreed less often regarding the presence of fat (Κ = 0.48), as well as regarding the presence of necrosis, heterogeneity, and the overall impression (Κ = 0.15, 0.24, and 0.26, respectively). CT characteristics correlated with benignity included round shape (p = 0.02), an overall radiologic impression of a benign lesion (p < 0.0001), the presence of fat (p = 0.01), and a precontrast attenuation of less than 10 Hounsfield units (p < 0.0001). The latter two of these characteristics were highly specific for benign pathology (93% and 100%, respectively). CONCLUSION: Our study suggests that CT has the ability to consistently identify characteristics significantly correlated with benign vs. malignant adrenal tumors.
Assuntos
Neoplasias das Glândulas Suprarrenais/diagnóstico por imagem , Adenoma Adrenocortical/diagnóstico por imagem , Carcinoma Adrenocortical/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Neoplasias das Glândulas Suprarrenais/patologia , Adenoma Adrenocortical/patologia , Carcinoma Adrenocortical/patologia , Idoso , Meios de Contraste , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Estudos RetrospectivosRESUMO
BACKGROUND: Patients with anaplastic thyroid cancer (ATC) have a dismal prognosis, despite systemic cytotoxic chemotherapy. The objective of this study was to investigate the efficacy and safety of targeted therapy in ATC patients when used outside of a clinical trial. METHODS: This is a retrospective review from April 2015 to May 2016 at a single academic institution where 16 ATC patients receiving targeted therapy outside of a clinical trial were studied. Ten patients (eight BRAF wild type and two BRAFV600E mutant tumors) were started on lenvatinib, and six with BRAFV600E-mutated tumors received a combination of dabrafenib plus trametinib. Best response evaluated by RECIST v1.1, progression-free survival, and overall survival were determined. Adverse events were evaluated for safety. RESULTS: The majority of patients (63%) were men, and all had distant metastases or radiation-resistant primary disease at the time of treatment. In the entire cohort, 6/16 (38%) had a partial response, 6/16 (38%) had stable disease, and 2/16 (12%) had progressive disease. Two (12%) patients died before restaging. Median follow-up time was 11.8 months. Median progression-free survival was 3.7 months [confidence interval 1.8-7.6] in the entire cohort, 2.7 months for lenvatinib, and 5.2 months for dabrafenib plus trametinib. Median OS was 6.3 months [confidence interval 1.8-7.6] for the entire cohort, 3.9 months for lenvatinib, and 9.3 months for dabrafenib plus trametinib. Adverse events were as expected and manageable. CONCLUSIONS: Targeted therapies, lenvatinib, and dabrafenib plus trametinib (for BRAFV600E mutants) may provide clinical benefit in ATC patients who are unable to participate in clinical trials, and toxicities are manageable.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Imidazóis/uso terapêutico , Oximas/uso terapêutico , Compostos de Fenilureia/uso terapêutico , Piridonas/uso terapêutico , Pirimidinonas/uso terapêutico , Quinolinas/uso terapêutico , Carcinoma Anaplásico da Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Prognóstico , Intervalo Livre de Progressão , Proteínas Proto-Oncogênicas B-raf/genética , Estudos Retrospectivos , Carcinoma Anaplásico da Tireoide/genética , Carcinoma Anaplásico da Tireoide/patologia , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/patologia , Resultado do TratamentoAssuntos
Neoplasias do Córtex Suprarrenal , Carcinoma Adrenocortical , Carcinoma de Células Renais , Neoplasias Renais , Neoplasias do Córtex Suprarrenal/cirurgia , Carcinoma Adrenocortical/cirurgia , Carcinoma de Células Renais/patologia , Procedimentos Cirúrgicos de Citorredução , Humanos , Neoplasias Renais/patologiaRESUMO
We describe a comprehensive genomic characterization of adrenocortical carcinoma (ACC). Using this dataset, we expand the catalogue of known ACC driver genes to include PRKAR1A, RPL22, TERF2, CCNE1, and NF1. Genome wide DNA copy-number analysis revealed frequent occurrence of massive DNA loss followed by whole-genome doubling (WGD), which was associated with aggressive clinical course, suggesting WGD is a hallmark of disease progression. Corroborating this hypothesis were increased TERT expression, decreased telomere length, and activation of cell-cycle programs. Integrated subtype analysis identified three ACC subtypes with distinct clinical outcome and molecular alterations which could be captured by a 68-CpG probe DNA-methylation signature, proposing a strategy for clinical stratification of patients based on molecular markers.
Assuntos
Neoplasias do Córtex Suprarrenal/genética , Carcinoma Adrenocortical/genética , Genoma Humano/genética , Genômica/métodos , Adolescente , Neoplasias do Córtex Suprarrenal/patologia , Neoplasias do Córtex Suprarrenal/terapia , Carcinoma Adrenocortical/patologia , Carcinoma Adrenocortical/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Metilação de DNA , Intervalo Livre de Doença , Feminino , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica , Predisposição Genética para Doença/genética , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Avaliação de Resultados em Cuidados de Saúde , Prognóstico , Adulto JovemRESUMO
Thymic neuroendocrine carcinomas are the most common mediastinal neuroendocrine tumor. These malignancies are not often diagnosed by fine-needle aspiration (FNA), as they are more commonly diagnosed by biopsy or excision. We describe a case of a FNA of a paratracheal mass from a 38-year-old man who presented with Cushing syndrome. A low-grade neuroendocrine carcinoma with oncocytic features was diagnosed, which was later confirmed by excision of the thymus, anterior mediastinal and paratracheal soft tissue, and lymph nodes. Oncocytic features in these tumors are a rare finding and bring metastatic medullary thyroid carcinomas as well as other metastases into the differential diagnosis. The prognosis of neuroendocrine carcinomas in this location is worse than neuroendocrine carcinomas in other areas, and close follow-up is recommended.
Assuntos
Carcinoma Neuroendócrino/patologia , Síndrome de Cushing/patologia , Timoma/patologia , Neoplasias do Timo/patologia , Hormônio Adrenocorticotrópico/biossíntese , Adulto , Biópsia por Agulha Fina/métodos , Carcinoma Neuroendócrino/metabolismo , Carcinoma Neuroendócrino/cirurgia , Síndrome de Cushing/metabolismo , Diagnóstico Diferencial , Humanos , Masculino , Prognóstico , Timoma/metabolismo , Timoma/cirurgia , Neoplasias do Timo/metabolismo , Neoplasias do Timo/cirurgiaRESUMO
Chronic liver diseases (CLDs) encompass a wide range of illnesses, including nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, and viral hepatitis. Deterioration of liver capacity, with subsequent progression into cirrhosis and hepatocellular carcinoma (HCC), ultimately leads to a further decrease in the hepatic reserve. The Child-Turcotte-Pugh scoring system is the standard tool for assessing underlying liver reserve capacity in routine practice and in clinical trials of CLD and HCC. In this review, we highlight the clinical significance of insulin-like growth factor-I (IGF-I) and the growth hormone (GH) signaling pathway in HCC. IGF-I could be a marker for liver reserve capacity in CLDs and HCC in clinical practice. This approach could improve the risk assessment and stratifications of patients on the basis of their underlying liver reserve, either before active treatment in routine practice or before they are enrolled in clinical trials.
RESUMO
INTRODUCTION: In patients with refractory adrenocorticotropic hormone-dependent Cushing's syndrome,we evaluated steroidogenesis inhibition (SI) and bilateral adrenalectomy (BA) to predict which patients might benefit most from each treatment modality. METHODS: Clinical data from patients treated 1970-2012 were reviewed retrospectively by treatment group (SI or SI+BA). Validated severity scales were used to calculate metabolic (M) score (hypokalemia, hyperglycemia, hypertension, proximal muscle weakness) and adverse events (AE) score (thrombosis, fracture, infection). RESULTS: A total of 65 patients (16 pituitary, 49 ectopic) were treated with SI+BA (n = 21,32%) or SI alone (n = 44,68%). Presenting M scores and source of adrenocorticotropic hormone excess (ectopic versus pituitary) were similar. Both groups improved metabolically after treatment. Over one-third of AEs in the SI+BA group occurred within 12 months of presentation. Half (n = 24, 55%) of the patients treated with SI died (median survival, 24.0 months). Steroid excess contributed to 71% of complications. Six SI+BA patients died (29%), including all 3 patients with recurrent Cushing's syndrome after BA. Minor perioperative complications occurred in 7 patients (33%). CONCLUSION: Posttreatment M and AE scores improved for all patients and 70% of AEs occurred in SI+BA patients within 12 months of presentation, emphasizing the importance of early operative intervention. These data argue for the safety and efficacy of early BA in selected patients with uncontrollable Cushing's syndrome.