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1.
Ann Surg ; 269(4): 741-747, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-29334561

RESUMO

BACKGROUND: Fluorodeoxyglucose (F-FDG) positron emission tomography/computed tomography (PET/CT) imaging is recommended in patients with metastatic pheochromocytoma (PC) and paraganglioma (PGL). There are no data on whether routine preoperative F-FDG PET/CT in all patients with PC/PGL impacts surgical management. OBJECTIVE: The aim of this study was to determine whether routine preoperative F-FDG PET/CT imaging affects the surgical management of patients with PC/PGLs. METHODS: We analyzed clinical, biochemical, genetic, and anatomic imaging data in 93 consecutive patients with PC/PGL who collectively underwent a total of 100 operations and who had preoperative F-FDG PET/CT imaging. RESULTS: Of 100 operations, preoperative F-FDG PET/CT showed additional lesions compared to anatomic imaging in 15 cases. These patients were more likely to undergo an open surgical approach (P < 0.05). Presence of genetic mutation, redo operations, sex, age, or tumor size had no significant association with finding additional lesions on F-FDG PET/CT. CONCLUSIONS: Additional lesions detected on preoperative F-FDG-PET/CT imaging have an impact on the surgical approach in patients with PC/PGLs. Therefore, surgeons should routinely obtain F-FDG-PET/CT imaging in patients with PC/PGL to allow for a more precise surgical intervention.


Assuntos
Neoplasias das Glândulas Suprarrenais/diagnóstico por imagem , Neoplasias das Glândulas Suprarrenais/cirurgia , Adrenalectomia/métodos , Fluordesoxiglucose F18/uso terapêutico , Paraganglioma/diagnóstico por imagem , Paraganglioma/cirurgia , Feocromocitoma/diagnóstico por imagem , Feocromocitoma/cirurgia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Compostos Radiofarmacêuticos/uso terapêutico , Adolescente , Adulto , Idoso , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Paraganglioma/secundário , Feocromocitoma/secundário , Medicina de Precisão , Cuidados Pré-Operatórios , Estudos Prospectivos , Adulto Jovem
2.
Gastroenterology ; 154(4): 998-1008.e1, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29155309

RESUMO

BACKGROUND & AIMS: Survival times vary among patients with neuroendocrine tumors (NETs) - even among those with the same site, stage, and grade of primary tumor. This makes it difficult to select treatment for patients with unresectable NETs because some patients can survive decades without treatment. 68Gallium-DOTATATE positron emission tomography with computed tomography (68Ga-DOTATATE PET/CT) is a sensitive imaging technique for detection of NETs. We investigated the prognostic accuracy of 68Ga-DOTATATE PET/CT-based analysis of tumor volume in patients with NETs. METHODS: We performed a prospective study of 184 patients with NETs (128 [69.6%] with metastases and 11 patients [6.0%] with locally advanced disease) at the National Institutes of Health Clinical Center (Bethesda, MD) from 2013 through 2017. All patients underwent 68Ga-DOTATATE PET/CT image analysis and total 68Ga-DOTATATE-Avid tumor volume (68Ga-DOTATATE TV) was determined. We also measured fasting serum chromogranin A, neuron-specific enolase, gastrin, glucagon, vasoactive intestinal peptide, pancreatic polypeptide, and 24-hour urinary 5-hydroxyindoleacetic acid levels in all patients. Disease progression was defined as a new lesion or a growth of a known lesion during the interval between baseline 68Ga-DOTATATE PET/CT scan and follow-up imaging (14.0 ± 6.1 months; range, 1-35 months). The primary outcomes were progression-free survival (PFS) and disease-specific mortality during a median follow-up time of 18 months (range, 4-35 months). RESULTS: We found an inverse correlation between quartiles of 68Ga-DOTATATE TV and PFS (P = .001) and disease-specific survival (P = .002). A 68Ga-DOTATATE TV of 7.0 mL or more was associated with higher odds of disease progression (hazard ratio, 3.0; P = .04). A 68Ga-DOTATATE TV of 35.8 mL or more was associated with increased risk of disease-specific death (hazard ratio, 10.6) in multivariable analysis (P = .01), as well as in subgroup analysis of patients with pancreatic NETs. CONCLUSIONS: In a prospective study, we demonstrated the prognostic utility of 68Ga-DOTATATE TV in a large cohort of patients with NETs, in terms of PFS and disease-specific mortality.


Assuntos
Neoplasias Gastrointestinais/diagnóstico por imagem , Tumores Neuroendócrinos/diagnóstico por imagem , Compostos Organometálicos/administração & dosagem , Neoplasias Pancreáticas/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Compostos Radiofarmacêuticos/administração & dosagem , Adulto , Idoso , Distribuição de Qui-Quadrado , Progressão da Doença , Intervalo Livre de Doença , Feminino , Neoplasias Gastrointestinais/mortalidade , Neoplasias Gastrointestinais/patologia , Neoplasias Gastrointestinais/terapia , Humanos , Estimativa de Kaplan-Meier , Masculino , Maryland , Pessoa de Meia-Idade , Análise Multivariada , Tumores Neuroendócrinos/mortalidade , Tumores Neuroendócrinos/secundário , Tumores Neuroendócrinos/terapia , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/terapia , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco , Fatores de Tempo , Carga Tumoral
3.
Surgery ; 165(1): 50-57, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30327187

RESUMO

BACKGROUND: There are conflicting reports on whether familial nonmedullary thyroid cancer is more aggressive than sporadic nonmedullary thyroid cancer. Our aim was to determine if the clinical and pathologic characteristics of familial nonmedullary thyroid cancer are different than nonmedullary thyroid cancer. METHODS: We compared patients with familial nonmedullary thyroid cancer to a cohort of 53,571 nonmedullary thyroid cancer patients from the Surveillance, Epidemiology, and End Results database. RESULTS: A total of 78 patients with familial nonmedullary thyroid cancer from 31 kindreds presented at a younger age (P = .04) and had a greater rate of T1 disease (P = .019), lymph node metastasis (P = .002), and the classic variant of papillary thyroid cancer on histology (P < .001) compared with the Surveillance, Epidemiology, and End Results cohort. Patients with ≥3 affected family members presented at a younger age (P = .04), had a lesser female-to-male ratio (P = .04), and had a greater rate of lymph node metastasis (P = .009). Compared with the Surveillance, Epidemiology, and End Results cohort, we found a higher prevalence of lymph node metastasis in familial nonmedullary thyroid cancer index cases (P = .003) but not in those diagnosed by screening ultrasonography (P = .58). CONCLUSION: Patients with familial nonmedullary thyroid cancer present at a younger age and have a greater rate of lymph node metastasis. The treatment for familial nonmedullary thyroid cancer should be more aggressive in patients who present clinically and in those who have ≥3 first-degree relatives affected.


Assuntos
Carcinoma Medular/congênito , Neoplasia Endócrina Múltipla Tipo 2a/patologia , Câncer Papilífero da Tireoide/patologia , Neoplasias da Glândula Tireoide/patologia , Adulto , Distribuição por Idade , Carcinoma Medular/epidemiologia , Carcinoma Medular/patologia , Carcinoma Medular/cirurgia , Estudos de Coortes , Feminino , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Neoplasia Endócrina Múltipla Tipo 2a/epidemiologia , Neoplasia Endócrina Múltipla Tipo 2a/cirurgia , Esvaziamento Cervical/estatística & dados numéricos , Programa de SEER , Distribuição por Sexo , Câncer Papilífero da Tireoide/epidemiologia , Câncer Papilífero da Tireoide/cirurgia , Neoplasias da Glândula Tireoide/epidemiologia , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia/estatística & dados numéricos , Estados Unidos/epidemiologia
4.
JAMA Surg ; 154(1): 40-45, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30267071

RESUMO

Importance: Neuroendocrine tumors (NETs) express somatostatin receptors, which can be targeted with radiolabeled peptides. In a variety of solid tumors, radioguided surgery (RGS) has been used to guide surgical resection. Gallium 68 (68Ga) dota peptides have been shown to be more accurate than other radioisotopes for detecting NETs. A pilot study previously demonstrated the feasibility and safety of 68Ga-dotatate RGS for patients with NETs. Objective: To evaluate what intraoperative techniques and thresholds define positive lesions that warrant resection during 68Ga-dotatate RGS. Design, Setting, and Participants: This prospective cohort study, conducted between October 23, 2013, and February 14, 2018, included 44 patients with NETs who underwent 68Ga-dotatate RGS. Intervention: Gallium 68-dotatate RGS. Main Outcomes and Measures: The in vivo and ex vivo tumor to background ratio (TBR) was assessed for resected lesions and correlated with the histopathologic findings. Results: Forty-four patients (22 women and 22 men; mean [SD] age, 51.0 [13.7] years) had 133 lesions detected on preoperative imaging scans, with a diagnosis of a pancreatic NET (19 of 44 [43%]), gastrointestinal NET (22 of 44 [50%]), and pheochromocytoma or paraganglioma (3 of 44 [7%]). The TBR was obtained by normalizing to the omentum (106 of 133 [79.7%]) or other solid organs (27 of 133 [20.3%]). The omentum had a significantly lower mean (SD) count than other solid organs for background count activity 3 hours after injection (22.1 [17.0] vs 34.5 [39.0]; P < .001). The lesions containing NETs had a higher TBR than those that did not contain NETs (18.9 vs 4.4; P < .001). On a receiver operating characteristic curve analysis, a TBR of 2.5 had a sensitivity of 90% and a specificity of 25%, and a TBR of 16 had a sensitivity of 54% and a specificity of 81%. Conclusions and Relevance: A TBR of 2.5 or greater is a highly sensitive threshold for indicating a lesion to be consistent with a NET on histologic findings and thus warranting surgical resection. The omentum should be used as the background count activity for 68Ga-dotatate RGS for patients with abdominal NETs.


Assuntos
Neoplasias Gastrointestinais/cirurgia , Tumores Neuroendócrinos/cirurgia , Neoplasias Pancreáticas/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Compostos Organometálicos , Paraganglioma/cirurgia , Feocromocitoma/cirurgia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Tomografia por Emissão de Pósitrons/métodos , Estudos Prospectivos , Compostos Radiofarmacêuticos , Cirurgia Assistida por Computador/métodos , Resultado do Tratamento
5.
Nucl Med Mol Imaging ; 53(2): 144-147, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31057686

RESUMO

A 36-year-old male patient initially presented with hypertension, tinnitus, bilateral carotid masses, a right jugular foramen, and a periaortic arch mass with an elevated plasma dopamine level but an otherwise normal biochemical profile. On surveillance MRI 4 years after initial presentation, he was found to have a 2.2-cm T2 hyperintense lesion with arterial enhancement adjacent to the gallbladder, which demonstrated avidity on 68Ga-DOTATATE PET/CT and retrospectively on 18F-FDOPA PET/CT but was non-avid on 18F-FDG PET/CT. Biochemical work-up including plasma catecholamines, metanephrines, and chromogranin A levels were found to be within normal limits. This lesion was surgically resected and was confirmed to be a paraganglioma (PGL) originating from the gallbladder wall on histopathology. Pheochromocytoma (PHEO) and PGL are rare tumors of the autonomic nervous system. Succinate dehydrogenase subunit D (SDHD) pathogenic variants of the succinate dehydrogenase complex are usually involved in parasympathetic, extra-adrenal, multifocal head, and neck PGLs. We report an unusual location of PGL in the gallbladder associated with SDHD mutation which could present as a potential pitfall on 18F-FDOPA PET/CT as its normal excretion occurs through biliary system and gallbladder. This case highlights the superiority of 68Ga-DOTATATE in comparison to 18F-FDOPA and 18F-FDG in the detection of SDHD-related parasympathetic PGL. ClinicalTrials.gov Identifier: NCT00004847.

6.
Surgery ; 163(1): 191-196, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29126554

RESUMO

BACKGROUND: Our knowledge of the susceptibility genes for pheochromocytomas/paragangliomas has increased; however, data on its impact on surgical decision-making has not been described. The aim of this study was to determine the effect of routine preoperative genetic testing on the operative intervention in patients with pheochromocytomas/paragangliomas. METHODS: One-hundred-eight patients diagnosed with pheochromocytomas/paragangliomas who underwent 118 operations had preoperative genetic testing for 9 known pheochromocytoma/paraganglioma susceptibility genes. A retrospective analysis of a prospective database was performed to evaluate clinical factors associated with the surgical approach selected and the outcome of the surgical intervention. RESULTS: In 51 patients (47%), a germline mutation was detected and one-third had no family history of pheochromocytoma/paraganglioma. In 77 operations (65%), it was the first operative intervention for the disease site (60 laparoscopic, 17 open), and 41 (35%) were reoperative interventions (36 open, 5 laparoscopic). For initial operations, variables associated with whether an open or laparoscopic approach was used were tumor size (P = .009) and presence of germline mutation (P = .042). Sixty-eight adrenal operations were performed (54 total, 14 cortical-sparing). Variables significantly associated with a cortical-sparing adrenalectomy being performed were the presence of germline mutation (P = .006) and tumor size (P = .013). CONCLUSION: Preoperative knowledge of the germline mutation status affects the surgical approach and extent of adrenalectomy.


Assuntos
Neoplasias das Glândulas Suprarrenais/cirurgia , Adrenalectomia/estatística & dados numéricos , Testes Genéticos/estatística & dados numéricos , Paraganglioma/cirurgia , Feocromocitoma/cirurgia , Adolescente , Neoplasias das Glândulas Suprarrenais/genética , Adrenalectomia/métodos , Adulto , Idoso , Criança , Pré-Escolar , Mutação em Linhagem Germinativa , Humanos , Pessoa de Meia-Idade , Paraganglioma/genética , Feocromocitoma/genética , Cuidados Pré-Operatórios , Estudos Retrospectivos , Adulto Jovem
7.
Surgery ; 163(1): 31-34, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29108698

RESUMO

BACKGROUND: Hereditary primary hyperparathyroidism may be syndromic or nonsyndromic (familial isolated hyperparathyroidism). Recently, germline activating mutations in the GCM2 gene were identified in a subset of familial isolated hyperparathyroidism. This study examined the clinical and biochemical characteristics and the treatment outcomes of GCM2 mutation-positive familial isolated hyperparathyroidism as compared to sporadic primary hyperparathyroidism. METHODS: We performed a retrospective analysis of clinical features, parathyroid pathology, and operative outcomes in 18 patients with GCM2 germline mutations and 457 patients with sporadic primary hyperparathyroidism. RESULTS: Age at diagnosis, sex distribution, race/ethnicity, and preoperative serum calcium concentrations were similar between the 2 groups. The preoperative serum levels of intact parathyroid hormone was greater in patients with GCM2-associated primary hyperparathyroidism (239 ± 394 vs 136 ± 113, P = .005) as were rates of multigland disease and parathyroid carcinoma in the GCM2 group (78% vs 14.3%, P < .001 and 5% vs 0%, P = .04, respectively), but the biochemical cure rate was less in the GCM2 group (86% vs 99%, P < .001). CONCLUSION: GCM2-associated primary hyperparathyroidism patients have greater preoperative parathyroid hormone levels, a greater rate of multigland disease, a lesser rate of biochemical cure, and a substantial risk of parathyroid carcinoma. Knowledge of these clinical characteristics could optimize the surgical management of GCM2-associated familial isolated hyperparathyroidism.


Assuntos
Hiperparatireoidismo Primário/genética , Proteínas Nucleares/genética , Fatores de Transcrição/genética , Adolescente , Adulto , Idoso , Feminino , Mutação em Linhagem Germinativa , Humanos , Hiperparatireoidismo Primário/patologia , Masculino , Pessoa de Meia-Idade , Glândulas Paratireoides/patologia , Estudos Retrospectivos , Adulto Jovem
8.
J Clin Endocrinol Metab ; 103(4): 1631-1638, 2018 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-29294023

RESUMO

Context: Patients with von Hippel-Lindau (vHL) disease caused by a missense VHL mutation have a more severe phenotype compared with other VHL mutation types. Objective: To define pancreatic neuroendocrine tumor (PNET) aggressiveness according to VHL genotype. Design: A prospective natural history study. Setting: The National Institutes of Health clinical center. Patients: Patients with vHL disease, pancreatic manifestations, and germline missense VHL gene mutations. Intervention: In-silico prediction of VHL mutation via five computational prediction models. Patients with >80% prediction for disease-causing mutations in all models [high predicted risk (HPR)] were compared with others [low predicted risk (LPR)]. Main Outcome Measure: Rates of metastases, surgical intervention, and disease progression. Results: Sixty-nine patients were included: 2 developed metastases, 12 needed surgery, and 31 had disease progression during a median follow-up of 60 months (range 13 to 84 months). Thirteen patients were excluded for low prediction reliability. In the remaining 56 patients (45 with PNETs, 11 with pancreatic cysts), the HPR group (n = 13) had a higher rate of disease progression than the LPR group (n = 43) in multivariable analysis (hazard ratio 3.6; 95% confidence interval, 1.1 to 11.9; P = 0.037). The HPR group also had a higher risk of developing metastases (P = 0.015). Among patients with codon 167 hotspot mutations (n = 26), those in the HPR group had a higher risk for disease progression (P = 0.03) than other patients. Conclusions: Computational models for predicting the impact of missense VHL gene mutations may be used as a prognostic factor in patients with PNETs in the context of vHL disease.


Assuntos
Análise Mutacional de DNA/métodos , Mutação , Neoplasias Pancreáticas/genética , Proteína Supressora de Tumor Von Hippel-Lindau/genética , Doença de von Hippel-Lindau/genética , Neoplasias das Glândulas Suprarrenais/genética , Neoplasias das Glândulas Suprarrenais/patologia , Adulto , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Simulação por Computador , Progressão da Doença , Feminino , Hemangioblastoma/genética , Hemangioblastoma/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Pâncreas/patologia , Neoplasias Pancreáticas/patologia , Feocromocitoma/genética , Feocromocitoma/patologia , Prognóstico , Estudos Prospectivos , Reprodutibilidade dos Testes , Doença de von Hippel-Lindau/patologia
9.
Endocrine ; 61(3): 422-427, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29923016

RESUMO

PURPOSE: It has been proposed that rebound hyperglycemia after resection of insulinoma indicates a biochemical cure. However, there is scant objective data in the literature on the rate and need for intervention in hyperglycemia in patients undergoing resection of insulinoma. The goal of our study was to evaluate the rate of postoperative hyperglycemia, any predisposing factors, and the need for intervention in a prospective cohort study of all patients undergoing routine glucose monitoring. METHODS: A retrospective analysis of 33 patients who had an insulinoma resected and who underwent routine postoperative monitoring of blood glucose (every hour for the first six hours then every four hours for the first 24 h) was performed. Hyperglycemia was defined as glucose greater than 180 mg/dL (10 mmol/l). RESULTS: Twelve patients (36%) developed hyperglycemia within 24 h (range 1-16 h). In patients with hyperglycemia, the mean maximum plasma glucose level was 221.5 mg/dL (range 97-325 mg/dL) (12.3 mmol/l), and four (33%) patients were treated with insulin. There was no significant difference in age, gender, body mass index (BMI), tumor size, biochemical profile, or surgical approach and extent of pancreatectomy between patients who developed hyperglycemia and those who did not. Pre-excision and post-excision intraoperative insulin levels were evaluated in 14 of 33 patients. The percentage decrease of the intraoperative insulin levels was not significantly different between patients who developed hyperglycemia and those who did not. All patients with postoperative hyperglycemia had normalization of their glucose levels, and none were discharged on anti-hyperglycemic agents. CONCLUSIONS: Hyperglycemia is common after insulinoma resection, and a subset of patients require transient treatment with insulin.


Assuntos
Procedimentos Cirúrgicos do Sistema Digestório/efeitos adversos , Hiperglicemia/epidemiologia , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Insulinoma/cirurgia , Neoplasias Pancreáticas/cirurgia , Adulto , Idoso , Glicemia , Feminino , Humanos , Hiperglicemia/tratamento farmacológico , Hiperglicemia/etiologia , Incidência , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/tratamento farmacológico , Complicações Pós-Operatórias/epidemiologia , Período Pós-Operatório , Estudos Retrospectivos
10.
J Am Coll Surg ; 226(5): 933-938, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29408534

RESUMO

BACKGROUND: Approximately 10% of patients with primary hyperparathyroidism (PHPT) have hereditary disease. Hereditary PHPT may be syndromic (MEN1, 2, and 4 and hyperparathyroidism-jaw tumor syndrome) or non-syndromic (familial isolated PHPT). There are limited data on the probability of testing positive for genetic mutation based on clinical presentation. The aim of this study was to determine potential associations between clinical and biochemical features and mutation in susceptibility genes for PHPT in patients with a family history of PHPT. STUDY DESIGN: A retrospective analysis of 657 patients who had an initial parathyroidectomy for PHPT at a tertiary referral center. Logistic regression analyses were performed in 205 patients with a family history of PHPT to identify factors associated with a positive genetic test. RESULTS: Of 657 patients, 205 (31.2%) had a family history of PHPT. Of those 205 patients, 123 (60%) had a germline mutation detected (91 MEN1, 14 CDC73, and 18 GCM2). In univariate analysis, younger age (45 years and younger), male sex, multigland disease, and parathyroid carcinoma were associated with positive germline mutation; biochemical cure after an initial parathyroidectomy was less frequent in patients with familial PHPT (96.2% vs 89.2%; p = 0.005). In multivariable analysis, age 45 years and younger, male sex, and multigland disease were independent factors associated with positive genetic testing. CONCLUSIONS: In addition to a family history of PHPT, male sex, age 45 years and younger, and presence of multigland disease, should prompt physicians to offer the opportunity for genetic counseling and testing, as it could influence the management of patients with PHPT.


Assuntos
Testes Genéticos , Hiperparatireoidismo Primário/genética , Adulto , Fatores Etários , Feminino , Predisposição Genética para Doença , Mutação em Linhagem Germinativa , Humanos , Hiperparatireoidismo Primário/cirurgia , Masculino , Pessoa de Meia-Idade , Paratireoidectomia , Probabilidade , Estudos Retrospectivos
11.
J Clin Endocrinol Metab ; 102(1): 195-199, 2017 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-27805844

RESUMO

Context: Reliable localization of insulinoma is critical for successful treatment. Objective: This study compared the accuracy of 68Gallium DOTA-(Tyr3)-octreotate (Ga-DOTATATE) positron emission tomography (PET)/computed tomography (CT) to anatomic imaging modalities, selective arterial secretagogue injection (SASI), and intraoperative ultrasound (IO ultrasound) and palpation for localizing insulinoma in patients who were biochemically cured. Design, Setting, and Patients: We conducted a retrospective analysis of 31 patients who had an insulinoma. The results of CT, magnetic resonance imaging (MRI), ultrasound, IO ultrasound, 68Ga-DOTATATE PET/CT, SASI, and operative findings were analyzed. Intervention, Main Outcome Measures, and Results: The insulinomas were correctly localized in 17 out of 31 (55%) patients by CT, in 17 out of 28 (61%) by MRI, in 6 out of 28 (21%) by ultrasound, and in 9 out of 10 (90%) by 68Ga-DOTATATE. In 29 of 31 patients (93.5%) who had IO ultrasound, an insulinoma was successfully localized. Thirty patients underwent SASI, and the insulinoma was regionalized in 28 out of 30 patients (93%). In 19 out of 23 patients (83%), manual palpation identified insulinoma. In patients who had all 4 noninvasive imaging studies, CT was concordant with 68Ga-DOTATATE in 6 out of 9 patients (67%), MRI in 8 out of 9 (78%), ultrasound in 0 out of 9; the lesion was only seen by 68Ga-DOTATATE in 1 out of 9 (11%). Conclusions: 68Ga-DOTATATE PET/CT identifies most insulinomas and may be considered as an adjunct imaging study when all imaging studies are negative and when a minimally invasive surgical approach is planned.


Assuntos
Processamento de Imagem Assistida por Computador/métodos , Insulinoma/diagnóstico por imagem , Insulinoma/diagnóstico , Compostos Organometálicos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Compostos Radiofarmacêuticos , Adulto , Idoso , Estudos de Coortes , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Adulto Jovem
12.
Eur J Endocrinol ; 176(5): 575-582, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28289088

RESUMO

OBJECTIVE: To determine the association between neuroendocrine tumor (NET) biomarker levels and the extent of disease as assessed by 68Ga DOTATATE PET/CT imaging. DESIGN: A retrospective analysis of a prospective database of patients with NETs. METHODS: Fasting plasma chromogranin A (CgA), neuron-specific enolase (NSE), gastrin, glucagon, vasoactive intestinal peptide (VIP) and pancreatic polypeptide (PP), and 24-h urinary 5-hydroxyindoleacetic acid (5-HIAA) levels were measured. Correlation between biomarkers and total 68Ga-DOTATATE-avid tumor volume (TV) was analyzed. RESULTS: The analysis included 232 patients. In patients with pancreatic NETs (n = 112), 68Ga-DOTATATE TV correlated with CgA (r = 0.6, P = 0.001, Spearman). In patients with multiple endocrine neoplasia type 1 (n = 39), 68Ga-DOTATATE TV correlated with glucagon (r = 0.5, P = 0.01) and PP levels (r = 0.5, P = 0.049). In patients with von Hippel-Lindau (n = 24), plasma VIP (r = 0.5, P = 0.02) and PP levels (r = 0.7, P < 0.001) correlated with 68Ga-DOTATATE TV. In patients with small intestine NET (SINET, n = 74), 68Ga-DOTATATE TV correlated with CgA (r = 0.5, P = 0.02) and 5-HIAA levels (r = 0.7, P < 0.001), with 5-HIAA ≥8.1 mg/24 h associated with metastatic disease with high positive (81.8%) and negative (85.7%) predictive values (P = 0.001). 68Ga-DOTATATE TV in patients with NET of unknown primary (n = 16) and those with NET of other primary location (n = 30) correlated with 5-HIAA levels (r = 0.8, P = 0.002 and r = 0.7, P = 0.02 respectively). CONCLUSIONS: Our data supports the use of specific NET biomarkers based on the site of the primary NET and the presence of hereditary syndrome-associated NET. High urinary 5-HIAA levels indicate the presence of metastatic disease in patients with SINET.


Assuntos
Biomarcadores Tumorais/metabolismo , Tumores Neuroendócrinos/diagnóstico por imagem , Tumores Neuroendócrinos/metabolismo , Adulto , Biomarcadores Tumorais/análise , Estudos de Coortes , Bases de Dados Factuais , Feminino , Humanos , Ácido Hidroxi-Indolacético/urina , Imageamento por Ressonância Magnética , Masculino , Imagem Multimodal , Neoplasia Endócrina Múltipla/diagnóstico por imagem , Neoplasia Endócrina Múltipla/metabolismo , Metástase Neoplásica , Compostos Organometálicos , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/metabolismo , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Estudos Retrospectivos
13.
J Clin Endocrinol Metab ; 101(10): 3559-3563, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27504852

RESUMO

CONTEXT: Insulinomas are usually due to a solitary tumor, but they can be challenging to localize. CASE DESCRIPTION: A 66-year-old woman presented with a 1-year history of episodic neuroglycopenic hypoglycemia and was suspected of having an insulinoma. On a supervised fast, she was found to be hypoglycemic at 39 mg/dL, with an insulin of 40 µU/mL 26 hours into the fast and a proinsulin of 35 pmol/L. Contrast-enhanced computed tomography and magnetic resonance imaging did not localize a pancreatic lesion. Intra-arterial calcium stimulation testing showed a step-up of venous insulin levels at injection of the superior mesenteric artery and proximal and mid-splenic artery, and a 68Ga-DOTATATE positron emission tomography/computed tomography showed focal uptake in the neck of the pancreas with a standardized uptake value of 12. Despite negative intraoperative pancreatic palpation and ultrasound, the patient underwent an extended distal pancreatectomy with normalization of biochemical levels and resolution of her symptoms. Pathology showed four subcentimeter neuroendocrine tumors that were positive for insulin, consistent with a diagnosis of multiple microadenomas. CONCLUSIONS: Multiple microadenomas are a rare cause of hyperinsulinemic hypoglycemia and localization, and resection of these tumors may be facilitated by multimodal imaging.


Assuntos
Insulinoma/diagnóstico por imagem , Neoplasias Pancreáticas/diagnóstico por imagem , Idoso , Feminino , Humanos , Insulinoma/sangue , Insulinoma/cirurgia , Imageamento por Ressonância Magnética , Imagem Multimodal , Pancreatectomia , Neoplasias Pancreáticas/sangue , Neoplasias Pancreáticas/cirurgia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada
14.
Thyroid ; 26(6): 831-5, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-27094616

RESUMO

BACKGROUND: Gallium-68 (Ga-68) DOTATATE is a radiolabeled peptide-imaging modality that targets the somatostatin receptor (SSTR), especially subtype 2 (SSTR2). Benign and malignant thyroid tumors have been observed to express SSTR. The aim of this study was to evaluate the frequency and clinical significance of incidental atypical thyroid uptake as detected by Ga-68 DOTATATE positron emission tomography/computed tomography (PET/CT). METHODS: A retrospective analysis was conducted of a prospective study in which 237 patients underwent Ga-68 DOTATATE PET/CT as part of a work-up for metastatic and unknown primary neuroendocrine tumors. The types of uptake in the thyroid gland (focal/diffuse) and maximum standardized uptake value (SUVmax) levels were evaluated and compared with the background uptake in the liver and salivary glands. RESULTS: Of 237 patients, 26 (11%) had atypical thyroid uptake as detected by Ga-68 DOTATATE PET/CT. There were no significant clinical or biochemical variables associated with atypical thyroid uptake. Fourteen (54%) patients had positive focal uptake, and 12 (46%) patients had diffuse uptake. Of the 14 patients with atypical focal uptake, 10 (71%) had thyroid nodules on the corresponding side, as detected by anatomic imaging. Three of 10 patients (21%) were found to have papillary thyroid cancer, and seven (70%) had adenomatoid nodules. Of the 12 patients with diffuse increased uptake, six (50%) had a history of hypothyroidism, five (42%) had chronic lymphocytic thyroiditis, and one (8%) had nontoxic multinodular goiter. CONCLUSIONS: Patients with an incidental focal abnormal thyroid uptake on Ga-68 DOTATATE PET/CT scan should have further clinical evaluation to exclude a diagnosis of thyroid cancer.


Assuntos
Carcinoma Papilar/diagnóstico por imagem , Bócio/diagnóstico por imagem , Hipotireoidismo/diagnóstico por imagem , Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Nódulo da Glândula Tireoide/diagnóstico por imagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Compostos Organometálicos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Estudos Retrospectivos , Adulto Jovem
15.
J Heart Valve Dis ; 14(3): 423-32, 2005 May.
Artigo em Inglês | MEDLINE | ID: mdl-15974538

RESUMO

For over 30 years, animal models have remained a central critical component in the pre-clinical safety evaluation of prosthetic heart valves developed for use in humans. Though many advances have been made in valve design, no ideal replacement prosthesis has yet been developed. As a result, valve manufacturers continue to address issues relating to thrombogenicity, structural integrity, fluid dynamics and calcification in their designs. Many animal models have been developed to examine these issues, including dog, pig, calf and sheep, yet no standard model has been accepted. Recently, the International Standard Organization has provided guidelines in document 5840 to address cardiovascular implants. The aim of this report is to provide a summary of the current state of pre-clinical valve evaluation in animals. Changes in ISO 5840 will be addressed that have occurred between 1998 and the present date, and the role of current available animal models. The aim also is to provide rational guidance in the selection of appropriate animal models to match the purpose of valve implantation studies.


Assuntos
Próteses Valvulares Cardíacas , Modelos Animais , Animais , Bovinos , Aprovação de Equipamentos , Cães , Estudos de Avaliação como Assunto , Guias como Assunto , Humanos , Desenho de Prótese , Segurança , Ovinos , Suínos
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