RESUMO
BACKGROUND: Adrenal venous sampling (AVS) is recommended before adrenalectomy for patients with primary aldosteronism (PA) over 35 years old. The literature examining contralateral suppression (CoS) on AVS in predicting surgical outcomes is conflicting. We examined the presence of CoS in patients who underwent adrenalectomy while adjusting for clinical and biochemical factors associated with a clinical cure of hypertension (ccHTN). METHODS: We performed a retrospective review of patients with successful AVS who underwent unilateral adrenalectomy for PA at a quaternary referral center. Patients were excluded if they had overt cortisol co-secretion, or inadequate follow-up. We first evaluated the aldosterone resolution score (ARS) in predicting ccHTN in our cohort. Next, the receiver-operator characteristic analysis (ROC) was used to determine the optimal contralateral suppression index (CSI) cutoff to define CoS. We performed univariable and multivariable analyses of factors associated with ccHTN. The primary outcome was ccHTN defined as blood pressure less than 140/90 mmHg, and off blood pressure medications. RESULTS: Of the 102 patients on bivariable analysis, age, sex, duration of HTN, number of medications, preoperative systolic blood pressure, and creatinine level were associated with ccHTN. ROC analysis of ARS had an AUC of 0.850 (p < 0.001). On multivariable analysis, only ARS remained associated with ccHTN (OR 3.40, 95% CI 1.20-9.61, p = 0.021). CSI was not significantly associated with ccHTN on ROC, bivariable, or multivariable analyses. CONCLUSION: The presence of CoS was not useful in predicting ccHTN following unilateral adrenalectomy for PA in our cohort. After adjusting for clinical and biochemical factors, ARS remains a useful predictor for ccHTN.
Assuntos
Hiperaldosteronismo , Glândulas Suprarrenais , Adrenalectomia , Adulto , Aldosterona , Humanos , Hiperaldosteronismo/diagnóstico , Hiperaldosteronismo/cirurgia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
The better understanding of the biological behavior of multiple endocrine neoplasia type 1 (MEN1) organ manifestations and the increase in clinical experience warrant a revision of previously published guidelines. Duodenopancreatic neuroendocrine neoplasias (DP-NENs) are still the second most common manifestation in MEN1 and, besides NENs of the thymus, remain a leading cause of death. DP-NENs are thus of main interest in the effort to reevaluate recommendations for their diagnosis and treatment. Especially over the last 2 years, more clinical experience has documented the follow-up of treated and untreated (natural-course) DP-NENs. It was the aim of the international consortium of experts in endocrinology, genetics, radiology, surgery, gastroenterology, and oncology to systematically review the literature and to present a consensus statement based on the highest levels of evidence. Reviewing the literature published over the past decade, the focus was on the diagnosis of F- and NF-DP-NENs within the MEN1 syndrome in an effort to further standardize and improve treatment and follow-up, as well as to establish a "logbook" for the diagnosis and treatment of DP-NENs. This shall help further reduce complications and improve long-term treatment results in these rare tumors. The following international consensus statement builds upon the previously published guidelines of 2001 and 2012 and attempts to supplement the recommendations issued by various national and international societies.
Assuntos
Consenso , Neoplasias Duodenais , Neoplasia Endócrina Múltipla Tipo 1 , Neoplasias Pancreáticas , Neoplasias Duodenais/diagnóstico , Neoplasias Duodenais/terapia , Humanos , Neoplasia Endócrina Múltipla Tipo 1/diagnóstico , Neoplasia Endócrina Múltipla Tipo 1/terapia , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/terapiaRESUMO
BACKGROUND: Li-Fraumeni syndrome is a cancer predisposition syndrome caused by germline TP53 tumor suppressor gene mutations, with no previous association with pancreatic neuroendocrine tumors (PNETs). Here we present the first case of PNET associated with Li-Fraumeni syndrome. CASE PRESENTATION: This is a 43-year-old female who underwent laparoscopic distal pancreatectomy at age 39 for a well-differentiated grade 2 cystic PNET. When the patient was 41 years old, her seven-year-old daughter was found to have an astrocytoma and a germline TP53 mutation. While undergoing surveillance with 68Gallium-DOTATATE positron emission tomography/computed tomography for her PNET, the patient was found to have a large choroid plexus papilloma in her right temporal lobe. She underwent genetic counseling and testing that identified a germline pathogenic variant in TP53, leading to the diagnosis of Li-Fraumeni syndrome. Her PNET had a hemizygous pathogenic TP53 mutation with loss of the wild-type alternate allele, consistent with loss of heterozygosity and the two-hit hypothesis. She was enrolled in a Li-Fraumeni syndrome protocol and continues surveillance screening with our service. CONCLUSIONS: This is the first PNET reported in association with Li-Fraumeni syndrome. Pancreatic cancer risk is elevated in this syndrome, and our case highlights the need for vigilance in screening for pancreatic neoplasms in these patients.
Assuntos
Genótipo , Síndrome de Li-Fraumeni/diagnóstico , Tumores Neuroendócrinos/diagnóstico , Neoplasias Pancreáticas/diagnóstico , Adulto , Feminino , Genes p53/genética , Predisposição Genética para Doença , Mutação em Linhagem Germinativa/genética , Heterozigoto , Humanos , Síndrome de Li-Fraumeni/complicações , Síndrome de Li-Fraumeni/genética , Tumores Neuroendócrinos/complicações , Tumores Neuroendócrinos/genética , Neoplasias Pancreáticas/complicações , Neoplasias Pancreáticas/genética , LinhagemRESUMO
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 TumoralAssuntos
Neoplasias do Íleo , Procedimentos Cirúrgicos Minimamente Invasivos , Tumores Neuroendócrinos , Humanos , Tumores Neuroendócrinos/cirurgia , Tumores Neuroendócrinos/mortalidade , Tumores Neuroendócrinos/patologia , Taxa de Sobrevida , Neoplasias do Íleo/cirurgia , Neoplasias do Íleo/mortalidade , Neoplasias do Íleo/patologia , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , PrognósticoRESUMO
OBJECTIVE: To report long-term follow-up of patients with multiple endocrine neoplasia type 1 (MEN1) and nonfunctioning pancreatic neuroendocrine tumors (NF-PET). BACKGROUND: Pancreaticoduodenal tumors occur in almost all patients with MEN1 and are a major cause of death. The natural history and clinical outcome are poorly defined, and management is still controversial for small NF-PET. METHODS: Clinical outcome and tumor progression were analyzed in 46 patients with MEN1 with 2âcm or smaller NF-PET who did not have surgery at the time of initial diagnosis. Survival data were analyzed using the Kaplan-Meier method. RESULTS: Forty-six patients with MEN1 were followed prospectively for 10.7â±â4.2 (meanâ±âstandard deviation) years. One patient was lost to follow-up and 1 died from a cause unrelated to MEN1. Twenty-eight patients had stable disease and 16 showed significant progression of pancreaticoduodenal involvement, indicated by increase in size or number of tumors, development of a hypersecretion syndrome, need for surgery (7 patients), and death from metastatic NF-PET (1 patient). The mean event-free survival was 13.9â±â1.1 years after NF-PET diagnosis. At last follow-up, none of the living patients who had undergone surgery or follow-up had evidence of metastases on imaging studies. CONCLUSIONS: Our study shows that conservative management for patients with MEN1 with NF-PET of 2âcm or smaller is associated with a low risk of disease-specific mortality. The decision to recommend surgery to prevent tumor spread should be balanced with operative mortality and morbidity, and patients should be informed about the risk-benefit ratio of conservative versus aggressive management when the NF-PET represents an intermediate risk.
Assuntos
Tratamento Conservador , Neoplasia Endócrina Múltipla Tipo 1/terapia , Neoplasias Pancreáticas/terapia , Adulto , Tomada de Decisão Clínica , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Neoplasia Endócrina Múltipla Tipo 1/mortalidade , Neoplasias Pancreáticas/mortalidade , Estudos Prospectivos , Resultado do TratamentoRESUMO
BACKGROUND: The prognosis and behavior of pancreatic neuroendocrine tumors (PNETs) vary and may be divergent even at the same stage or tumor grade. Markers of systemic inflammatory response are readily available and are inexpensive, and have been shown to be prognostic factors in several cancers. OBJECTIVE: The aim of this study was to evaluate the prognostic utility of markers of systemic inflammatory response in patients with PNETs. METHODS: A prospective study of 97 patients with PNETs was performed (median follow-up of 15 months, range 12-73 months). Neutrophil-to-lymphocyte ratios (NLRs) and lymphocyte-to-monocyte ratios (LMRs) were calculated at baseline and preoperatively. The primary outcome measures were progression-free survival (PFS) and recurrence-free survival (RFS) after curative resection. RESULTS: Among all patients, an NLR > 2.3 [hazard ratio (HR) 2.53, 95% confidence interval (CI) 1.05-6.08, p = 0.038] and the presence of distant metastases (HR 2.8, 95% CI 1.26-6.21, p = 0.012) were independent predictors of disease progression. Among patients who did not undergo surgery during the study period, both platelet-to-lymphocyte ratio (PLR) > 160.9 (HR 5.86, 95% CI 1.27-27.08, p = 0.023) and mean platelet volume > 10.75 fL (HR 6.63, 95% CI 1.6-27.48, p = 0.009) were independently associated with worse PFS on multivariable analysis. Among patients who underwent complete resection, an LMR < 3.46 was associated with a worse RFS (HR 9.72, 95% CI 1.19-79.42, p = 0.034). CONCLUSIONS: PLR > 160.9 and an MPV > 10.75 fL at baseline are independent predictors of disease progression, while an LMR < 3.46 is an independent predictor of tumor recurrence after complete resection in patients with PNETs.
Assuntos
Monócitos , Tumores Neuroendócrinos/sangue , Tumores Neuroendócrinos/secundário , Neutrófilos , Neoplasias Pancreáticas/sangue , Neoplasias Pancreáticas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Biomarcadores/sangue , Progressão da Doença , Intervalo Livre de Doença , Feminino , Humanos , Inflamação/sangue , Contagem de Linfócitos , Masculino , Volume Plaquetário Médio , Pessoa de Meia-Idade , Tumores Neuroendócrinos/cirurgia , Neoplasias Pancreáticas/cirurgia , Contagem de Plaquetas , Período Pós-Operatório , Valor Preditivo dos Testes , Período Pré-Operatório , Intervalo Livre de Progressão , Estudos Prospectivos , Curva ROC , Adulto JovemRESUMO
BACKGROUND: The aim of this study was to describe first experiences and changes in management using continuous intraoperative neuromonitoring (C-IONM) in thyroid and parathyroid surgery. METHOD: Retrospective analysis of patients who underwent surgery with C-IONM since 2012. Surgical maneuvers were modified when electrophysiologic events occurred. Patients with persistent loss of signal (LOS) underwent postoperative laryngoscopy. RESULTS: One hundred and one patients (of 1586 neck surgeries) were included and 19 had events: In 13 these were temporary (resolved before end of surgery) and led to intraoperative modifications in surgical approach; in all cases traction was released, and in 8, recurrent laryngeal nerve (RLN) approach was changed [superior approach (2), inferior approach (2), both (4)]. Six patients had persistent LOS (5.9%, present at end of procedure), with RLN palsy (RLNP) on postoperative day 1: In three, LOS occurred at electrode placement on the vagus nerve, leading to distal placement of the electrode allowing ipsilateral dissection under continuous monitoring; all three had complete recovery at 6 months. In the three other patients, LOS occurred on the RLN: one probable thermal, one traction lesion and one accidental section of the anterior RLN branch. The RLN recovered within 6 months in two patients, and in the third, RLNP persisted after 6 months (1/101 = 1%). CONCLUSION: C-IONM provides real-time evaluation of the RLN function, allowing for adaptation of surgical maneuvers to prevent RLNP. It seems particularly useful in difficult cases like redo neck surgery, invasive thyroid cancer and intrathoracic or large goiter. Care should be given at electrode placement on the vagus nerve.
Assuntos
Monitorização Intraoperatória/métodos , Traumatismos do Nervo Laríngeo Recorrente/prevenção & controle , Nervo Laríngeo Recorrente/fisiopatologia , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia/métodos , Paralisia das Pregas Vocais/prevenção & controle , Adulto , Idoso , Dissecação/métodos , Feminino , Humanos , Complicações Intraoperatórias/prevenção & controle , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/prevenção & controle , Estudos Retrospectivos , Paralisia das Pregas Vocais/fisiopatologiaRESUMO
OBJECTIVE: Valproic acid (VA) is a histone deacetylase (HDAC) inhibitor that has antiproliferative effects on several types of cancer, including thyroid cancer. In addition, VA has been reported to upregulate the sodium-iodine symporter in thyroid cancer cells and increases radioiodine uptake in preclinical studies. The aim of this study was to assess the antiproliferative effects of VA and to evaluate if VA can increase the radioiodine uptake in patients with advanced, radioiodine-negative thyroid cancer. DESIGN: An open-label Simon two-stage phase II trial. PATIENTS AND MEASUREMENTS: Valproic acid was administered orally, and doses were adjusted to maintain serum trough levels between 50 and 100 mg/l for 10 weeks, followed by injections of recombinant human thyroid-stimulating hormone and a radioiodine uptake scan. Anatomical imaging studies were performed at week 16 to assess tumour response and radioiodine therapy in patients with increased radioiodine uptake. RESULTS: Thirteen patients with a median age of 66 years (50-78 years) were enrolled and evaluated. Seven patients had papillary thyroid cancer (PTC), two had follicular variant PTC, two had follicular thyroid cancer, and two had Hürthle cell carcinoma. None of the 10 patients who completed the 10-week treatment had increased radioiodine uptake at their tumour sites. Three patients were taken off the study prior to the 10-week radioiodine uptake scan: one with grade-3 hepatic toxicity, one with disease progression and one for noncompliance. Four of 13 patients had decreased stimulated serum thyroglobulin with VA treatment. None of the patients had complete or partial responses based on Response Evaluation Criteria in Solid Tumors (RECIST), and six patients had disease progression. CONCLUSIONS: Valproic acid does not increase radioiodine uptake and does not have anticancer activity in patients with advanced, radioiodine-negative thyroid cancer of follicular cell origin.
Assuntos
Adenocarcinoma Folicular/tratamento farmacológico , Inibidores de Histona Desacetilases/uso terapêutico , Neoplasias da Glândula Tireoide/tratamento farmacológico , Ácido Valproico/uso terapêutico , Adenocarcinoma Folicular/sangue , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Radioisótopos do Iodo , Masculino , Pessoa de Meia-Idade , Tireoglobulina/sangue , Neoplasias da Glândula Tireoide/sangueRESUMO
BACKGROUND: To report the association between thoracic duct ligation and acute pancreatitis. The association between sudden stop of lymphatic flow and pancreatitis has been established in experimental models. CASE PRESENTATION: A 57-year-old woman operated for thymoma presented a iatrogenic chylothorax. After thoracic duct ligation, she presented an acute pancreatitis which resolved after conservative treatment. The chylothorax disappeared within 4 days of thoracic duct ligation. CONCLUSIONS: This is the first report of acute pancreatitis following thoracic duct ligation. The pancreas and digestive tract should be assessed in symptomatic patients after thoracic duct ligation.
Assuntos
Quilotórax/cirurgia , Pancreatite/etiologia , Ducto Torácico/cirurgia , Procedimentos Cirúrgicos Torácicos/efeitos adversos , Timoma/cirurgia , Neoplasias do Timo/cirurgia , Doença Aguda , Quilotórax/etiologia , Feminino , Humanos , Doença Iatrogênica , Ligadura/efeitos adversos , Pessoa de Meia-Idade , Pancreatite/terapiaRESUMO
BACKGROUND: Approximately 8-17 % of patients with von Hippel-Lindau (VHL) syndrome develop pancreatic neuroendocrine tumors (PNETs), with 11-20 % developing metastases. Tumor grade is predictive of prognosis. OBJECTIVE: The aim of this study was to determine if preoperative metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were associated with metastatic disease and tumor grade. METHODS: Sixty-two patients with VHL-associated PNETs prospectively underwent 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT). MTV, TLG, and maximum standardized uptake value (SUVmax) were measured using a semi-automatic method. Surgically resected PNETs were classified according to 2010 World Health Organization tumor grade classification. MTV, TLG, and SUVmax were analyzed by metastatic disease and tumor grade using the Mann-Whitney test. RESULTS: A total of 88 PNETs were identified by CT and 18F-FDG PET/CT, 10 of which were non-FDG-avid. Histologic grading was available for 20 surgical patients. Patients with metastatic PNETs had a higher TLG (median 25.9 vs. 7.7 mean SUV [SUVmean]*mL; p = 0.0092) compared with patients without metastasis, while patients with grade 2 PNETs had a higher MTV (median 6.9 vs. 2.6 mL; p = 0.034) and TLG (median 41.2 vs. 13.1 SUVmean*mL; p = 0.0035) compared with patients with grade 1 PNETs. No difference in tumor size or SUVmax was observed between the groups. CONCLUSIONS: Patients with metastatic PNETs have a higher TLG compared with patients without metastasis. Grade 2 PNETs have a higher MTV and TLG compared with grade 1 PNETs. Tumor size and SUVmax were not associated with grade. Volumetric parameters on 18F-FDG PET/CT may be useful in detecting higher grade PNETs with a higher malignant potential that may need surgical intervention.
Assuntos
Tumores Neuroendócrinos/diagnóstico por imagem , Tumores Neuroendócrinos/secundário , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/patologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Doença de von Hippel-Lindau/complicações , Adulto , Feminino , Fluordesoxiglucose F18 , Glicólise , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Tumores Neuroendócrinos/metabolismo , Tumores Neuroendócrinos/cirurgia , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/cirurgia , Período Pré-Operatório , Compostos Radiofarmacêuticos , Estudos RetrospectivosRESUMO
Major complications of thyroid and parathyroid surgery are recurrent laryngeal nerve injuries and definitive hypoparathyroidism. The use of intra-operative Indocyanine Green Angiography for confirmation of vascular status of the parathyroid gland is reported here.
Assuntos
Hiperparatireoidismo/cirurgia , Verde de Indocianina , Glândulas Paratireoides/diagnóstico por imagem , Paratireoidectomia/métodos , Angiografia , Humanos , Hiperparatireoidismo/diagnóstico por imagem , Monitorização Intraoperatória , Glândulas Paratireoides/irrigação sanguínea , Paratireoidectomia/efeitos adversos , Complicações Pós-Operatórias/etiologia , Traumatismos do Nervo Laríngeo Recorrente/etiologiaRESUMO
BACKGROUND: Surgery is the only definitive therapy for gastro-entero-pancreatic neuroendocrine tumors (GEPNETs), and achieving complete tumor resection is an important prognostic factor. Radiopharmaceuticals such as (68)Ga-DOTA peptides have been developed that offer superior accuracy for localization of GEPNETs. The study aim was to determine the feasibility of radio-guided surgery (RGS) using (68)Ga-DOTATATE in patients with primary and recurrent GEPNETs. METHODS: Fourteen patients with GEPNETs were enrolled onto a prospective study to determine the feasibility of RGS with (68)Ga-DOTATATE. Findings from preoperative imaging, intraoperative exploration, RGS, and pathology were analyzed. RESULTS: The median decay corrected target count rate was 172.6 (range 28.15-2341) for tumors, with a tumor-to-background ratio (TBR) of 4.46 (range 1.6-43.56). The median lesion size was 1.55 (range 0.5-15) cm. There was no significant correlation between preoperative imaging maximum standardized uptake value (SUVmax) of the lesions and TBR (Spearman r = - 0.01, p = 0.9), TBR and tumor size (Spearman r = 0.29, p = 0.14), and SUVmax and tumor size (Spearman r = 0.22, p = 0.28). The probe showed correct identification for gastric and small intestine neuroendocrine tumor (NET), including lymph node metastasis in 17 (81.0 %) of 21 cases, with a median TBR of 3.5 (1.6-40.2). For pancreatic NETs and lymph node metastasis, 16 (66.7 %) of 24 were correctly identified by RGS. CONCLUSIONS: Our study shows that RGS with (68)Ga-DOTATATE is feasible and correctly confirms bowel NETs and metastatic mesenteric lymph nodes. Further studies are needed to determine the benefit of RGS with (68)Ga-DOTATATE.
Assuntos
Neoplasias Intestinais/diagnóstico por imagem , Neoplasias Intestinais/cirurgia , Imagem Multimodal/métodos , Tumores Neuroendócrinos/diagnóstico por imagem , Tumores Neuroendócrinos/cirurgia , Compostos Organometálicos/farmacocinética , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/cirurgia , Compostos Radiofarmacêuticos/farmacocinética , Radioterapia Guiada por Imagem/métodos , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/cirurgia , Adulto , Idoso , Biomarcadores Tumorais , Estudos de Viabilidade , Feminino , Seguimentos , Humanos , Processamento de Imagem Assistida por Computador/métodos , Técnicas Imunoenzimáticas , Neoplasias Intestinais/metabolismo , Neoplasias Intestinais/patologia , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Tumores Neuroendócrinos/metabolismo , Tumores Neuroendócrinos/patologia , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Tomografia por Emissão de Pósitrons/métodos , Prognóstico , Estudos Prospectivos , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Distribuição Tecidual , Tomografia Computadorizada por Raios X/métodosRESUMO
BACKGROUND: Surgical resection remains the treatment of choice for carotid body tumors (CBTs). Although perioperative complications such as carotid artery injury and neurological deficits occur infrequently, they can be devastating. The aim of this study was to evaluate whether clinical factors or preoperative imaging findings can accurately predict perioperative complications. METHODS: Twenty CBTs were resected from 19 patients. Preoperative computed tomography (CT) and magnetic resonance imaging (MRI) of the neck were used to measure the degree of circumferential involvement of the CBT to the internal carotid artery (ICA), carotid artery narrowing, tumor length, tumor volume, and the distance from the tip of the C2 dens to the superior aspect of the CBT (dens-CBT). Operative reports and Shamblin classification (I-III) of each tumor were independently reviewed. Preoperative imaging features were compared to perioperative cranial nerve injury (CNI), rates of carotid artery injury, and major carotid artery repairs, as well as Shamblin classifications≥II. RESULTS: CNI was associated with a high-lying CBT (dens-CBT=1.8 vs. 2.9 cm, p<0.01). All four patients with CNI had a dens-CBT of <3 cm. Neither tumor length and tumor volume nor the involvement of the ICA (≥180° as measured by CT or MRI) was associated with CNI, carotid artery injury, major carotid artery repair, or Shamblin II or III classification. No carotid artery narrowing was observed in any of the cases. CONCLUSIONS: Preoperative measurement of the dens-CBT is helpful in identifying CBTs at risk for CNI after surgical resection.
Assuntos
Lesões das Artérias Carótidas/epidemiologia , Artéria Carótida Interna/diagnóstico por imagem , Tumor do Corpo Carotídeo/diagnóstico por imagem , Traumatismos dos Nervos Cranianos/epidemiologia , Complicações Intraoperatórias/epidemiologia , Procedimentos Cirúrgicos Vasculares/efeitos adversos , Adolescente , Adulto , Idoso , Artéria Carótida Interna/patologia , Tumor do Corpo Carotídeo/patologia , Tumor do Corpo Carotídeo/cirurgia , Estudos de Coortes , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Processo Odontoide/diagnóstico por imagem , Processo Odontoide/patologia , Estudos Retrospectivos , Fatores de Tempo , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Carga Tumoral , Adulto JovemRESUMO
BACKGROUND: Total thyroidectomy presents a risk of bilateral vocal cord paralysis, which can lead to compromised airway. Visual Recurrent Laryngeal Nerve (RLN) identification significantly decreases this risk of RLN lesion. Yet, an anatomically intact nerve is not always functional. Intraoperative neuromonitoring (IONM) allows to test in real time the function of the RLN. In case of loss of signal (LOS) on the first operated side, some authors recommend to stop the intervention. The purpose of this study was to characterize the operative strategy of the French-speaking surgeons in case of LOS on the first side in planned bilateral thyroidectomies. METHODS: An online questionnaire was sent to the surgeons of the French Association of Endocrine Surgeons (AFCE). RESULTS: We collected 69 responses (response rate: 42%). Forty-six surgeons (66%) used IONM. After a signal loss, 22% (N = 10) stopped the operation in all cases, 24% (N = 11) continued the operation in case of malignant disease and stopped in cases of benign disease, and 54% (N = 25) continued the operation contralaterally. CONCLUSIONS: The majority of surgeons continued the operation contralaterally as originally planned despite a loss of IONM signal at the end of the first side.
Assuntos
Monitorização Neurofisiológica Intraoperatória , Traumatismos do Nervo Laríngeo Recorrente/prevenção & controle , Tireoidectomia/efeitos adversos , Tireoidectomia/métodos , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cirurgiões , Inquéritos e Questionários , Paralisia das Pregas Vocais/prevenção & controleRESUMO
Pancreatic neuroendocrine tumors (PNETs) arise from neuroendocrine cells and are a rare class of heterogenous tumors with increasing incidence. The diagnosis, staging, treatment, and prognosis of PNETs depend heavily on identifying the histologic features and biological mechanisms. Here, the authors provide an overview of the diagnostic workup (biomarkers and imaging), grade, and staging of PNETs. The authors also explore associated genetic mutations and molecular pathways and describe updated guidelines on surgical and systemic treatment modalities.
Assuntos
Tumores Neuroendócrinos , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/cirurgia , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/patologia , Tumores Neuroendócrinos/cirurgia , Tumores Neuroendócrinos/diagnóstico , Tumores Neuroendócrinos/patologia , Estadiamento de Neoplasias , Pancreatectomia/métodos , PrognósticoRESUMO
Pancreatic neuroendocrine neoplasms (pNENs) are a heterogeneous group of tumors derived from multiple neuroendocrine origin cell subtypes. Incidence rates for pNENs have steadily risen over the last decade, and outcomes continue to vary widely due to inability to properly screen. These tumors encompass a wide range of functional and non-functional subtypes, with their rarity and slow growth making therapeutic development difficult as most clinically used therapeutics are derived from retrospective analyses. Improved molecular understanding of these cancers has increased our knowledge of the tumor biology for pNENs. Despite these advances in our understanding of pNENs, there remains a dearth of models for further investigation. In this review, we will cover the current field of pNEN models, which include established cell lines, animal models such as mice and zebrafish, and three-dimensional (3D) cell models, and compare their uses in modeling various disease aspects. While no study model is a complete representation of pNEN biology, each has advantages which allow for new scientific understanding of these rare tumors. Future efforts and advancements in technology will continue to create new options in modeling these cancers.
RESUMO
Typical (TC) and atypical carcinoids (AC) are the most common neuroendocrine tumors (NETs) of the lung. Because these tumors are rare, their management varies widely among Swiss centers. Our aim was to compare the management of Swiss patients before and after the publication of the expert consensus of the European Neuroendocrine Tumor Society (ENETS) in 2015. We used data from the Swiss NET registry from 2009 to 2021 with patients with TC and AC. Survival analysis was performed using the Kaplan-Meier method and log-rank test. Overall, 238 patients were included, 76% (180) thereof with TC and 24% (58) with AC, including 155 patients before and 83 patients after 2016. An increase in the use of functional imaging was observed, 16% (25) before and 35% (29) after 2016, p < 0.001. The presence of SST2A-receptors was determined more often: 32% (49 times) before 2016 and 47% (39 times) after, p = 0.019. Concerning therapy, higher removal of lymph nodes after 2016 was observed, 54% (83) before versus 78% (65) after, p < 0.001. Median overall survival for patients with AC was significantly shorter, with 89 months compared to 157 months for patients with TC, p < 0.001. While the implementation of a more standardized approach was observed over the years, there is still room for amelioration in the management of TC and AC in Switzerland.
RESUMO
Pancreatic neuroendocrine tumors (PNET) express high levels of somatostatin receptor type 2 (SSTR2), a unique target for both tumor imaging and therapy. This surface expression is lost in metastatic high-grade PNETs, making patients ineligible for SSTR2-targeted 177 Lutetium (Lu)-DOTATATE peptide receptor radionuclide therapy (PRRT), and represents an unmet clinical need. Here, we aimed to restore SSTR2 expression through the reversal of inhibitory epigenetic gene silencing to improve tumor responsiveness to PRRT. We first assessed human SSTR2 promoter methylation and expression levels in 96 patient samples. We then used three NET cell lines (QGP-1, BON-1, GOT-1) with variable SSTR2 expression profiles for functional in vitro studies using histone deacetylase inhibitors (HDACi). Finally, the QGP-1 xenograft mouse model, with low basal SSTR2 expression, was used to assess the therapeutic efficacy of combined HDACi and 177Lu-DOTATATE therapies. We confirm that SSTR expression is decreased and correlates with SSTR2 promoter methylation in patients with high-grade NETs. When exposed to HDACis, SSTR2 surface expression is increased in three NET cell lines in vitro. In an in vivo PNET xenograft model with low basal SSTR2 expression, our studies demonstrate significantly higher tumor uptake of SSTR2-targeted 177Lu-DOTATATE in animals pretreated with HDACis compared with controls. For the first time, we show that this higher tumor uptake results in significant antitumor response when compared with standard PRRT alone. These preclinical results provide a rationale for utilizing HDACi pretreatment to improve targeted radionuclide therapy in patients with SSTR2-negative, metastatic PNETs.
Assuntos
Tumores Neuroectodérmicos Primitivos , Tumores Neuroendócrinos , Neoplasias Pancreáticas , Humanos , Animais , Camundongos , Regulação para Cima , Tumores Neuroendócrinos/tratamento farmacológico , Tumores Neuroendócrinos/genética , Tumores Neuroendócrinos/radioterapia , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/radioterapiaRESUMO
Context: The identification of parathyroid tumor(s) in patients with persistent/recurrent primary hyperparathyroidism (PHPT) is critical for a successful reoperative surgery. If noninvasive studies (ultrasound, computed tomography, magnetic resonance imaging, sestamibi) fail to conclusively localize the tumor, invasive procedures (arteriography and selective venous sampling) are performed. Objective: To describe our experience with invasive studies for parathyroid tumor localization and provide follow-up data on selective arterial hypocalcemic stimulation with central venous sampling, a technique developed at our center. Methods: We identified patients who underwent preoperative invasive testing for localization of parathyroid tumor from 1991 to 2020. The result of each invasive localization study [arteriogram, hypocalcemic stimulation and selective venous sampling (SVS)] was categorized as true-positive, false-positive, and false-negative based on histology and biochemical outcome. Results: Ninety-four patients with 96 tumor occurrences underwent invasive testing for parathyroid tumor localization. Arteriogram, hypocalcemic stimulation, and SVS accurately localized the tumor in 47 of 94 (50%), 56 of 93 (60%), and 51 of 62 (82%) tumors, respectively. Hypocalcemic stimulation was more likely to correctly localize the tumor when arteriogram showed a blush [37 of 50 (74%) vs 19 of 43 (44%), P = .01]. When both arteriogram and hypocalcemic stimulation yielded concordant positive findings, SVS did not change management in the 18 cases in which all 3 were performed. Twelve patients remained with persistent PHPT; all had recurrent disease with multiple affected glands. Conclusion: Hypocalcemic stimulation is a useful adjunct in patients with PHPT who require invasive localization and can obviate the need for SVS. Clinical Trial number: NCT04969926.