RESUMO
BACKGROUND: In patients with low-risk differentiated thyroid cancer undergoing thyroidectomy, the postoperative administration of radioiodine (iodine-131) is controversial in the absence of demonstrated benefits. METHODS: In this prospective, randomized, phase 3 trial, we assigned patients with low-risk differentiated thyroid cancer who were undergoing thyroidectomy to receive ablation with postoperative administration of radioiodine (1.1 GBq) after injections of recombinant human thyrotropin (radioiodine group) or to receive no postoperative radioiodine (no-radioiodine group). The primary objective was to assess whether no radioiodine therapy was noninferior to radioiodine therapy with respect to the absence of a composite end point that included functional, structural, and biologic abnormalities at 3 years. Noninferiority was defined as a between-group difference of less than 5 percentage points in the percentage of patients who did not have events that included the presence of abnormal foci of radioiodine uptake on whole-body scanning that required subsequent treatment (in the radioiodine group only), abnormal findings on neck ultrasonography, or elevated levels of thyroglobulin or thyroglobulin antibodies. Secondary end points included prognostic factors for events and molecular characterization. RESULTS: Among 730 patients who could be evaluated 3 years after randomization, the percentage of patients without an event was 95.6% (95% confidence interval [CI], 93.0 to 97.5) in the no-radioiodine group and 95.9% (95% CI, 93.3 to 97.7) in the radioiodine group, a difference of -0.3 percentage points (two-sided 90% CI, -2.7 to 2.2), a result that met the noninferiority criteria. Events consisted of structural or functional abnormalities in 8 patients and biologic abnormalities in 23 patients with 25 events. Events were more frequent in patients with a postoperative serum thyroglobulin level of more than 1 ng per milliliter during thyroid hormone treatment. Molecular alterations were similar in patients with or without an event. No treatment-related adverse events were reported. CONCLUSIONS: In patients with low-risk thyroid cancer undergoing thyroidectomy, a follow-up strategy that did not involve the use of radioiodine was noninferior to an ablation strategy with radioiodine regarding the occurrence of functional, structural, and biologic events at 3 years. (Funded by the French National Cancer Institute; ESTIMABL2 ClinicalTrials.gov number, NCT01837745.).
Assuntos
Radioisótopos do Iodo/uso terapêutico , Neoplasias da Glândula Tireoide/radioterapia , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia , Adulto , Terapia Combinada , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Pescoço/diagnóstico por imagem , Prognóstico , Qualidade de Vida , Neoplasias da Glândula Tireoide/diagnóstico por imagem , UltrassonografiaRESUMO
PURPOSE: Bone metastases (BM) from differentiated thyroid carcinoma (DTC) impact negatively the quality of life and the life expectancy of patients. The aim of the study was (a) to evaluate the overall survival (OS) and prognostic factors of OS and (b) to assess predictive factors of complete BM response (C-BM-R) using radioiodine treatment (RAI) either alone or in association with focal treatment modalities. METHODS: A total of 178 consecutive DTC patients harbouring BM, treated between 1989 and 2015, were enrolled in this retrospective study conducted in two tertiary referral centers. OS analysis was performed for the whole cohort, and only the 145 considered non-RAI refractory patients at BM diagnosis were evaluated for C-BM-R following RAI. RESULTS: The median OS from BM diagnosis was 57 months (IQR: 24-93). In multivariate analysis, OS was significantly reduced in the case of T4 stage, 18FDG uptake by the BM and RAI refractory status. Among the 145 DTC considered non-RAI refractory patients at BM diagnosis, 46 patients (31.7%) achieved a C-BM-R following RAI treatment, either alone in 32 (18%) patients or in association with focal BM treatment modalities in 14. The absence of extra-skeletal distant metastasis and of 18FDG uptake in BM were predictive for C-BM-R. CONCLUSIONS: In nearly one-third of DTC patients with RAI avid BM, RAI alone or in combination with BM focal treatment can induce C-BM-R. The presence of 18FDG uptake in BM is associated with an absence of C-BM-R and with a poor OS. 18FDG PET-CT should be performed when BM is suspected.
Assuntos
Adenocarcinoma , Neoplasias Ósseas , Neoplasias da Glândula Tireoide , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/radioterapia , Neoplasias Ósseas/secundário , Fluordesoxiglucose F18 , Humanos , Radioisótopos do Iodo/uso terapêutico , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Qualidade de Vida , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/patologiaRESUMO
BACKGROUND: Vasoactive intestinal peptide-secreting tumor (VIPoma) is a very rare, life-threatening, functioning pancreatic neuroendocrine tumor (pNET). The efficacy of antitumor therapies against functioning symptoms and tumor burden have been poorly described in VIPoma. OBJECTIVE: Describe the impact of treatments on the secretory syndrome, tumor burden and survival in patients with VIPoma. METHODS: We retrospectively reviewed the records of patients with VIPoma treated in seven French expert centers between 1990 and 2016. Diagnostic of VIPoma was reassessed using strict criteria. We evaluated the antisecretory efficacy (>50 % decrease of daily bowel movements), and antitumor efficacy (RECIST 1.1) of all treatments received. RESULTS: Twenty-two patients were included. pNETs were mostly metastatic (77 %) and classified as grade 2 (83 %). Median follow-up was 78.2 months. Surgical excision of nonmetastatic VIPoma effectively controlled the secretory syndrome. Although 4/5 patients had metastatic recurrences, all patients were alive after median post-operative follow-up of 171 months. Among the 87 treatments received for metastatic VIPoma, curative-intent surgery (n = 14), somatostatin analogs alone (n = 11), chemotherapy (n = 23), transarterial liver embolization (TALE) (n = 14), everolimus (n = 10) and sunitinib (n = 7) achieved, respectively, 100 %, 67 %, 83 %, 50 %, 20 % and 100 % antisecretory efficacy. The 5-year OS rate was 63.6 %, with pejorative impact of higher Ki-67 index (P = 0.045) and higher plasma VIP concentration (P = 0.025). CONCLUSIONS: Surgical resection of localized VIPoma is effective but rarely curative. For metastatic VIPoma, curative-intent surgery, chemotherapy and sunitinib are the therapeutic options that best combined antitumor and antisecretory efficacies.
Assuntos
Neoplasias Hepáticas , Neoplasias Pancreáticas , Vipoma , Humanos , Neoplasias Pancreáticas/tratamento farmacológico , Estudos Retrospectivos , Sunitinibe , Vipoma/terapiaRESUMO
INTRODUCTION: The goal of this retrospective study was to investigate the potential link between diabetes mellitus (DM) and the recurrence of pancreatic neuroendocrine tumors (PanNET) following curative intent surgery. METHODS: We included patients who underwent surgical resection of nonmetastatic well-differentiated PanNET. Exacerbation of DM was defined as the postoperative occurrence of DM or worsening of preexisting DM. We explored the variables associated with PanNET recurrence-free survival (RFS). RFS was compared in a subset of patients with and without DM operated on by anatomical resection, after matching for the main prognostic factors. The impact of antidiabetic therapy on RFS was assessed. RESULTS: A total of 268 patients (median age 54.7, 40% men) were included. Most PanNET were sporadic (85%), G1 (61%), pT1/pT2 (79%), and pN0 (76%). Postoperative DM exacerbation occurred in 38 patients (14%), including 27 with new-onset DM. On multivariable analysis, DM exacerbation was independently associated with an increased risk of PanNET recurrence (HR 2.35, 95% CI [1.24-4.47], p = 0.009) after adjustment for age, multiplicity of tumors, grade, pT, and pN stages. Similar results were found when 27 patients with and 48 patients without DM exacerbation, matched for grade, pT stage and pN stage, were compared (HR 3.03, 95% CI [1.05-8.77], p = 0.032). The postoperative use of metformin tended to decrease the risk of recurrence (HR 0.59, 95% CI 0.24-1.47, p = 0.26). CONCLUSION: Patients with postoperative DM exacerbation may have an increased risk of PanNET recurrence. Closer follow-up might be beneficial in these patients. The protective role of metformin should be further explored.
Assuntos
Diabetes Mellitus , Recidiva Local de Neoplasia , Tumores Neuroendócrinos , Pancreatectomia , Neoplasias Pancreáticas , Complicações Pós-Operatórias , Adulto , Idoso , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/etiologia , Diabetes Mellitus/prevenção & controle , Feminino , Seguimentos , Humanos , Hipoglicemiantes/farmacologia , Masculino , Metformina/farmacologia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/patologia , Tumores Neuroendócrinos/epidemiologia , Tumores Neuroendócrinos/patologia , Tumores Neuroendócrinos/cirurgia , Avaliação de Resultados em Cuidados de Saúde , Pancreatectomia/efeitos adversos , Pancreatectomia/estatística & dados numéricos , Neoplasias Pancreáticas/epidemiologia , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/patologia , Intervalo Livre de Progressão , Estudos Retrospectivos , Exacerbação dos SintomasRESUMO
BACKGROUND: Neuroendocrine carcinomas (NECs) of the digestive tract are rare and aggressive tumours. In localised disease the treatment is surgery. Based on expert consensus, international guidelines recommend the administration of adjuvant chemotherapy combining etoposide and platinum derivatives, justified by the high risk of metastatic relapse. However, no clinical study has proven the benefit of neoadjuvant or adjuvant chemotherapy. OBJECTIVES: We aimed to evaluate the effect of neoadjuvant +/- adjuvant and adjuvant therapy in this indication. METHODS: We performed a retrospective observational French study to evaluate overall survival (OS) and disease-free survival (DFS), prognostic factors for survival, and chemotherapy toxicity. RESULTS: Seventy-three patients had surgical resection of a localised digestive NEC between January 1, 2000 and December 31, 2016. The majority of patients presented colorectal (35%) tumours and the median Ki-67 value was 70%. Forty-three patients received chemotherapy, either perioperative (neoadjuvant +/- adjuvant) or adjuvant. The median OS and DFS for the whole population was 24 and 9 months, respectively. The median OS and DFS for patients receiving chemotherapy was 62 and 13 months, respectively. Positive postoperative node status and Ki-67 ≥80% had a negative prognostic impact on OS and DFS. Administration of chemotherapy had a positive prognostic impact on OS and DFS. Sixteen grade 3/4 toxicities were reported without toxic death. CONCLUSIONS: Our results suggest a positive effect on survival of chemotherapy in resected digestive NECs, but further studies are needed to confirm these results.
Assuntos
Antineoplásicos/farmacologia , Carcinoma Neuroendócrino/tratamento farmacológico , Carcinoma Neuroendócrino/mortalidade , Neoplasias do Sistema Digestório/tratamento farmacológico , Neoplasias do Sistema Digestório/mortalidade , Avaliação de Resultados em Cuidados de Saúde , Adulto , Idoso , Antineoplásicos/efeitos adversos , Carcinoma Neuroendócrino/cirurgia , Quimioterapia Adjuvante , Neoplasias do Sistema Digestório/cirurgia , Feminino , França , Humanos , Antígeno Ki-67 , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Prognóstico , Intervalo Livre de Progressão , Estudos RetrospectivosRESUMO
OBJECTIVE: The primary endpoint was to analyze the predictive factors of lymph node involvement (LN+). BACKGROUND: Indications for additional right hemicolectomy (RHC) with lymph node (LN) resection after appendectomy for appendix neuroendocrine tumor (A-NET) remain controversial, especially for tumors between 1 and 2âcm in size. METHODS: National study including all patients with nonmetastatic A-NET diagnosed after January, 2010 in France. RESULTS: In all, 403 patients were included. A-NETs were: within tip (67%), body (24%) or base (9%) of the appendix; tumor size was <â1âcm (62%), 1 to 2âcm (30%), or >2âcm (8%); grade 1 (91%); mesoappendix involvement 3âmm (5%); lymphovascular (15%) or perineural (24%) invasion; and positive resection margin (8%). According to the European NeuroEndocrine Tumor Society (ENETS) recommendations, 85 patients (21%) should have undergone RHC. The agreement between ENETS guidelines and the multidisciplinary tumor board for complementary RHC was 89%. In all, 100 (25%) patients underwent RHC with LN resection, 26 of whom had LN+. Tumor size (best cut-off at 1.95âcm), lymphovascular and perineural invasion, and pT classifications were associated with LN+. Among the 44 patients who underwent RHC for a tumor of 1 to 2âcm in size, 8 (18%) had LN+. No predictive factor of LN+ (base, resection margins, grade, mesoappendix, lymphovascular, perineural involvement) was found in this subgroup of patients. CONCLUSIONS: In the largest study using the latest pathological criteria for completion RHC in A-NET, a quarter of patients had residual tumor. Further studies are warranted to demonstrate the survival impact of RHC in this setting.
Assuntos
Apendicectomia , Neoplasias do Apêndice/patologia , Neoplasias do Apêndice/cirurgia , Colectomia , Linfonodos/patologia , Tumores Neuroendócrinos/patologia , Tumores Neuroendócrinos/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Seguimentos , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Adulto JovemRESUMO
Background: Thermal ablation is a minimally invasive technique that is gradually acknowledged as an effective alternative to surgery to treat thyroid nodules. Two main techniques have been described: radiofrequency (RFA) and laser ablation. Objective: To evaluate the safety and efficacy of the two main techniques (RFA and laser ablation) for the treatment of benign thyroid nodules. Patients: This bicentric retrospective study included 166 consecutive patients, who received clinical, biological and ultrasound evaluations for thyroid nodules, from October 2013 to November 2017. Methods: One of the two techniques was proposed if a nodule was proven to be benign after fine needle aspiration cytology or micro-biopsy. Adverse events and outcomes (symptoms, nodule reduction) were assessed at 6 weeks and 6, 12, and 18 months after treatment. Results: One hundred and eighty-nine nodules (mean size 17.5 ± 16.9 mL, 86.1% palpable) were treated by RFA (n = 108 (57.1%)) or laser ablation (n = 81 (42.9%)) in 166 patients (80.1% women, mean age 51.7 years). Two cases of transient recurrent laryngeal nerve palsy, one hematoma, and two successfully drained abscesses (5/166 = 3%) were observed. Clinical symptoms improved significantly in the two groups (anterior cervical discomfort -83.6%, esthetic complaints -84.9% and dysphagia -86.4%). Nodule volume (mL) decreased significantly (baseline vs. 18 months) from 20.4 ± 18.6 to 5.8 ± 6.6 (-75%) in the RFA, and from 13.6 ± 13.3 to 3.4 ± 4.1 (-83.9%) in the laser ablation groups. Conclusions: Transient but potentially serious adverse events were reported in 3% of patients. A significant volumetric reduction was achieved with both techniques, regardless of nodule's characteristics, at 18 months.
Assuntos
Ablação por Cateter , Terapia a Laser , Nódulo da Glândula Tireoide/cirurgia , Abscesso/etiologia , Adulto , Ablação por Cateter/efeitos adversos , Doenças dos Nervos Cranianos/etiologia , Feminino , Hematoma/etiologia , Humanos , Nervos Laríngeos , Terapia a Laser/efeitos adversos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Resultado do TratamentoRESUMO
Oncocytic adrenocortical tumors are a rare subtype of adrenal tumors with challenging diagnosis and histoprognostic assessment. It is usually believed that oncocytic adrenocortical tumors have a more indolent clinical behavior than conventional adrenocortical tumors. As the Weiss score overestimates the malignancy of oncocytic adrenocortical tumors owing to intrinsic parameters, alternative scores have been proposed. The Lin-Weiss-Bisceglia score is currently recommended. We performed a large nationwide multicenter retrospective clinicopathologic study of oncocytic adrenocortical tumors. Among the 43 patients in our cohort, 40 patients were alive without disease, 2 patients died of their disease and 1 patient was alive with relapse after a median follow-up of 38 months (20-59). Our data revealed that over 50% of the oncocytic adrenocortical tumor cases were diagnosed as carcinoma whatever the classification systems used, including the Lin-Weiss-Bisceglia score. The exception is the Helsinki score, which incorporates the Ki-67 proliferation index and was the most specific prognostic score for oncocytic adrenocortical tumor malignancy without showing a loss in sensitivity. A comparison of malignant oncocytic adrenocortical tumors with conventional adrenocortical carcinomas matched for age, sex, ENS@T stage and surgical resection status showed significant better overall survival of malignant oncocytic adrenocortical tumors.
Assuntos
Adenoma Oxífilo/patologia , Neoplasias do Córtex Suprarrenal/patologia , Biomarcadores Tumorais/análise , Antígeno Ki-67/biossíntese , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos RetrospectivosRESUMO
OBJECTIVE: Mitotane/Op'DDD is used in the treatment of adrenocortical carcinoma and for other causes of hypercortisolism. Mitotane inhibits cortisol secretion and displays adrenolytic and antitumor actions. This compound is a metabolite of the pesticide and endocrine disruptor DDT (dichlorodiphenyltrichloroethane) and is classified among teratogenic compounds worldwide. However, little is known about its effects on human development. DESIGN: The outcome of four children exposed to mitotane during their intrauterine life was examined. PATIENTS: Patients having conceived while taking mitotane, or with detectable mitotane plasma levels, were retrospectively recruited via the French COMETE and FIRENDO networks. MEASUREMENTS: Mitotane in maternal plasma, adrenocortical hormones in children. RESULTS: Three women treated with mitotane gave birth to four children. During early pregnancy, all patients had detectable mitotane plasma levels (0.9, 2.4 and 6.7 mg/L, respectively). During pregnancy, no foetal malformations were detected. The four exposed newborns presented at birth with apparently normal adrenal function and genitalia. One twin female had a low birthweight. Evaluation at birth and after 3 months, 2 years and 7 years of follow-up showed no significant neurological abnormality. Evaluation of adrenocortical functions showed no cortisol deficiency. CONCLUSIONS: Unexpectedly, exposure of these four children to mitotane during foetal life seemed to have no clear teratogenic effect. However, considering the sub-therapeutic mitotane concentrations used here, the small number of cases, and because long-term follow-up is unknown, we strongly advise not to take mitotane during pregnancy and still recommend avoiding pregnancy, at least as long as mitotane plasma levels remain detectable.
Assuntos
Diclorodifenildicloroetano/toxicidade , Feto/efeitos dos fármacos , Mitotano/toxicidade , Adulto , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Gravidez , Estudos Retrospectivos , Adulto JovemRESUMO
BACKGROUND: There are no data from prospective studies focused exclusively on patients with advanced lung and thymic carcinoids. We aimed to assess the efficacy and safety of long-acting pasireotide and everolimus, administered alone or in combination, in patients with advanced carcinoids of the lung or thymus. METHODS: LUNA was a prospective, multicentre, randomised, open-label, phase 2 trial of adult patients (aged >18 years) with advanced (unresectable or metastatic), well differentiated carcinoid tumours of the lung or thymus, with radiological progression within 12 months before randomisation, and a WHO performance status of 0-2. At each centre, the investigator or their designee registered each patient using an interactive voice recognition system into one of the three treatment groups. The randomisation allocation sequence was generated by an external company; patients were randomly assigned (1:1:1) to receive treatment with long-acting pasireotide (60 mg intramuscularly every 28 days), everolimus (10 mg orally once daily), or both in combination, for the core 12-month treatment period. Patients were stratified by carcinoid type (typical vs atypical) and line of study treatment (first line vs others). The primary endpoint was the proportion of patients progression-free at month 9, defined as the proportion of patients with overall lesion assessment at month 9 showing a complete response, partial response, or stable disease according to local Response Evaluation Criteria in Solid Tumors, version 1.1, assessed in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. The trial is registered with ClinicalTrials.gov, number NCT01563354. The extension phase of the study is ongoing. FINDINGS: Between Aug 16, 2013, and Sept 30, 2014, 124 patients were enrolled from 36 centres in nine countries: 41 were allocated to the long-acting pasireotide group, 42 to the everolimus group, and 41 to the combination group. At month 9, the proportion of patients with an overall lesion assessment of complete response, partial response, or stable disease was 16 of 41 patients (39·0%, 95% CI 24·2-55·5) in the long-acting pasireotide group, 14 of 42 patients (33·3%, 19·6-49·5) in the everolimus group, and 24 of 41 patients (58·5%, 42·1-73·7) in the combination group. The most common grade 1-2 adverse events with a suspected association with long-acting pasireotide monotherapy were diarrhoea (15 [37%] of 41), hyperglycaemia (17 [41%]), and weight loss (8 [20%]); those with a suspected association with everolimus monotherapy were stomatitis (26 [62%] of 42) and diarrhoea (16 [38%]); and those suspected to be associated with combination treatment were hyperglycaemia (27 [66%] of 41]), diarrhoea (19 [46%]), and asthenia (8 [20%]). The most common grade 3-4 adverse events with a suspected association with long-acting pasireotide monotherapy were γ-glutamyltransferase increased (four [10%] of 41 patients), diarrhoea (three [7%]), and hyperglycaemia (three [7%]); those for everolimus were hyperglycaemia (seven [17%] of 42 patients), stomatitis (four [10%]), and diarrhoea (three [7%]); those for combination treatment were hyperglycaemia (nine [22%] of 41 patients) and diarrhoea (four [10%]). 11 patients died during the core 12-month treatment phase or up to 56 days after the last study treatment exposure date: two (5%) of 41 in the long-acting pasireotide group, six (14%) of 42 in the everolimus group, and three (7%) of 41 in the combination group. No deaths were suspected to be related to long-acting pasireotide treatment. One death in the everolimus group (acute kidney injury associated with diarrhoea), and two deaths in the combination group (diarrhoea and urinary sepsis in one patient, and acute renal failure and respiratory failure in one patient) were suspected to be related to everolimus treatment. In the latter patient, acute renal failure was not suspected to be related to everolimus treatment, but respiratory failure was suspected to be related. INTERPRETATION: The study met the primary endpoint in all three treatment groups. Safety profiles were consistent with the known safety profiles of these agents. Further studies are needed to confirm the antitumour efficacy of the combination of a somatostatin analogue with everolimus in lung and thymic carcinoids. FUNDING: Novartis Pharma AG.
Assuntos
Tumor Carcinoide/tratamento farmacológico , Everolimo/administração & dosagem , Neoplasias Pulmonares/tratamento farmacológico , Segurança do Paciente , Somatostatina/análogos & derivados , Neoplasias do Timo/tratamento farmacológico , Administração Oral , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Tumor Carcinoide/mortalidade , Tumor Carcinoide/patologia , Preparações de Ação Retardada/administração & dosagem , Intervalo Livre de Doença , Relação Dose-Resposta a Droga , Esquema de Medicação , Everolimo/efeitos adversos , Feminino , Humanos , Injeções Intramusculares , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Prognóstico , Estudos Prospectivos , Somatostatina/administração & dosagem , Somatostatina/efeitos adversos , Análise de Sobrevida , Neoplasias do Timo/mortalidade , Neoplasias do Timo/patologia , Resultado do TratamentoRESUMO
BACKGROUND: Laparoscopic adrenalectomy (LA) has become the standard technique for most indications. The aim of this study was to determine the predictive factors of intra- and postoperative complications in order to inform the orientation of patient to a surgeon with more experience in adrenal surgery. METHODS: From January 1994 to December 2013, 520 consecutive patients benefited from LA at Huriez Hospital, Lille, France. Each complication was graded according to the Dindo-Clavien-grade scale. The predictive factors of complications were determined by logistic regression. RESULTS: Fifty-two surgeons under the supervision of 5 senior surgeons (individual experience >30 LA) participated. Postoperative complications with a grade of ≥2 occurred in 52 (10 %) patients (29 (5.6 %) medical, 19 (3.6 %) surgical, and 4 (0.8 %) mixed complications) leading to 12 (2.3 %) reoperations. There was no postoperative death. Intraoperative complication happened in 81 (15.6 %) patients responsible for conversion to open adrenalectomy (OA) [odds ratio (OR) 13.9, CI 95 % 4.74-40.77, p < 0.001]. History of upper mesocolic or retroperitoneal surgery was predictive of intraoperative complication (OR 2.02, 1.05-3.91, p = 0.036). Lesion diameter ≥45 mm was predictive of intraoperative complication (OR 1.94, 1.19-3.15, p = 0.008), conversion to OA (OR 7.46, 2.18-25.47, p = 0.001), and adrenal capsular breach (OR 4.416, 1.628-11.983, p = 0.004). Conversion to OA was the main predictive factor of postoperative complications (OR 5.42, 1.83-16.01, p = 0.002). Under adequate supervision, the surgeon's individual experience and initial adrenal disease were not considered predictive of complications. CONCLUSION: Lesion diameter over 45 mm is the determinant parameter for guidance of patients to surgeons with more extensive experience.
Assuntos
Adrenalectomia/métodos , Complicações Intraoperatórias/etiologia , Laparoscopia/métodos , Complicações Pós-Operatórias/etiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Estudos Retrospectivos , Fatores de Risco , Adulto JovemRESUMO
BACKGROUND: Laparoscopic adrenalectomy (LA) is the standard treatment for benign adrenal lesions. The laparoscopic approach has also been increasingly accepted for adrenal metastases but remains controversial for adrenocortical carcinoma (ACC). In a retrospective cohort study we compared the outcome of LA versus open adrenalectomy (OA) in the treatment of stage I and II ACC. METHODS: This was a double cohort study comparing the outcome of patients with stage I/II ACC and a tumor size <10 cm submitted to LA or OA at Lille University Hospital referral center from 1985 to 2011. Main outcomes analyzed were: postoperative morbidity, overall survival, and disease-free survival. RESULTS: Among 111 consecutive patients operated on for ACC, 34 met the inclusion criteria. LA and OA were performed in 13 and 21 patients, respectively. Baseline patient characteristics (gender, age, tumor size, hormonal secretion) were similar between groups. There was no difference in postoperative morbidity, but patients in LA group were discharged earlier (p < 0.02). After a similar follow-up (66 ± 52 for LA and 51 ± 43 months for OA), Kaplan-Meier estimates of disease-specific survival and disease-free survival were identical in both groups (p = 0.65, p = 0.96, respectively). CONCLUSIONS: LA was associated with a shorter length of stay and did not compromise the long-term oncological outcome of patients operated on for stage I/II ACC ≤ 10 cm ACC. Our results suggest that LA can be safely proposed to patients with potentially malignant adrenal lesions smaller than 10 cm and without evidence of extra-adrenal extension.
Assuntos
Neoplasias do Córtex Suprarrenal/mortalidade , Adrenalectomia/mortalidade , Carcinoma Adrenocortical/mortalidade , Laparoscopia , Recidiva Local de Neoplasia/mortalidade , Complicações Pós-Operatórias , Neoplasias do Córtex Suprarrenal/patologia , Neoplasias do Córtex Suprarrenal/cirurgia , Carcinoma Adrenocortical/patologia , Carcinoma Adrenocortical/cirurgia , Adulto , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Fatores de TempoRESUMO
AIMS: To investigate the performance of two proposed methods for assessing the prognosis of poorly differentiated thyroid carcinomas (PDTC): the Turin proposal and Hiltzik's histological grade (HHG). This was done using a series of 82 thyroid carcinomas of follicular origin. RESULTS: The two methods were able to classify patients accurately into two different prognosis groups. Although the Turin proposal and HHG displayed discrepant cases, they provided similar prognostic information. The Turin proposal gave accurate numbers and thresholds of PTDC criteria (loss of follicular architecture and mitoses, necrosis or convoluted nuclei). One Turin criterion, convoluted nuclei, failed to provide any prognostic value. Hiltzik's histological grade was also a simple and reliable method, allowing detection of tumours with high-grade features (mitosis and/or tumour necrosis), notably some papillary carcinomas that displayed an intermediate prognosis. We show that Ki67 labelling (≥ 4%) was an independent factor and predictor of cause-specific survival. CONCLUSION: With similar performances in predicting prognosis, the Turin proposal and HHG provided complementary results in identifying a larger group of 'intermediate prognosis' thyroid carcinomas, which require adequate treatment and follow-up.
Assuntos
Adenocarcinoma Folicular/patologia , Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/patologia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mitose , Necrose/patologia , Gradação de Tumores , PrognósticoRESUMO
We describe the case of a 66-year-old woman treated with tyrosine kinase inhibitor Lenvatinib for thyroid carcinoma who had persistent proteinuria above 2 g/24 h despite maximal dose of angiotensin-converting enzyme inhibitor. We initiated a treatment with SGLT2 inhibitor Dapagliflozin. Three months after Dapagliflozin initiation, her proteinuria decreased to 1 g/24 h, and after 6 months of follow-up was 0.6 g/24 h. To our knowledge, this is the first case of successful proteinuria reduction with SGLT2i in a patient treated with Lenvatinib. Specific renal effects of SGLT2i seem promising and their effects on tyrosine kinase inhibitor renal adverse effects need to be validated in clinical trials involving cancer patients.
Assuntos
Antineoplásicos , Compostos Benzidrílicos , Glucosídeos , Compostos de Fenilureia , Quinolinas , Inibidores do Transportador 2 de Sódio-Glicose , Neoplasias da Glândula Tireoide , Humanos , Feminino , Idoso , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/patologia , Inibidores de Proteínas Quinases/efeitos adversos , Quinolinas/efeitos adversos , Proteinúria/induzido quimicamente , Proteinúria/tratamento farmacológico , Antineoplásicos/efeitos adversosRESUMO
CONTEXT: Pheochromocytoma and paraganglioma (PPGL) are rare neuroendocrine tumors with high heritability, justifying systematic genetic screening for a germline variant in one of the twenty predisposing genes described to date. PURPOSE: To describe the experience of one endocrine oncogenetic laboratory over a period of 21 years (2001-2022), from the beginning of PPGL genotyping with Sanger sequencing in 2001 to the implementation of next-generation sequencing (NGS). METHOD: The activity database of an academic oncogenetic laboratory was searched to extract patients/relatives identified with a pathogenic variant/likely pathogenic variant (PV/LPV) over a period of 21 years. Clinical and genetic data were compared. RESULTS: In total, 606 index cases with PPGL and 444 relatives were genotyped. Genotyping of index cases was performed by Sanger sequencing and gene deletion analysis in 327 cases and by NGS in 279. Germline PV/LPV spanning 10 genes was identified in 165 index cases (27.2%). Several recurrent PV/LPVs in SDHx were observed in non-related index cases, the most frequent being SDHD, c.170-1G>T (n=28). This subgroup showed great phenotypic variability both between and within families in terms of both tumor location and number. Four patients (1.1%) with PV/LPV in SDHx had 3PA (Pituitary Adenoma and pheochromocytoma/paraganglioma) syndrome. 258 relatives (58.1%) had inherited a PV/LPV in one driver gene. The rate of PV/LPV carriers who were symptomatic at first imaging evaluation was 32%, but varied between<20% in SDHB and SDHC and >50% in SDHD, VHL and MAX. CONCLUSION: Our experience confirmed previously established genotype-phenotype correlations, but also highlights atypical clinical presentations, even for the same genetic variant. These data must be taken into account for optimal patient follow-up and management.
Assuntos
Neoplasias das Glândulas Suprarrenais , Predisposição Genética para Doença , Mutação em Linhagem Germinativa , Paraganglioma , Feocromocitoma , Humanos , Feocromocitoma/genética , Feocromocitoma/epidemiologia , Paraganglioma/genética , Paraganglioma/epidemiologia , Neoplasias das Glândulas Suprarrenais/genética , Neoplasias das Glândulas Suprarrenais/epidemiologia , Adulto , Feminino , Masculino , Pessoa de Meia-Idade , Adolescente , Adulto Jovem , Testes Genéticos , Idoso , Sequenciamento de Nucleotídeos em Larga Escala , Criança , Genótipo , Succinato Desidrogenase/genéticaRESUMO
BACKGROUND: APECED syndrome is a rare disease caused by biallelic mutations of the AIRE gene, usually presenting with the triad "hypoparathyroidism-adrenal failure-chronic mucocutaneous candidiasis (CMC)" and non-endocrine manifestations. The aim of this study was to determine the molecular profile of the AIRE gene, the prevalence of rare manifestations and to characterize immunological disturbances in a French cohort. PATIENTS AND METHODS: A national, multicenter prospective observational study to collect genetic, clinical, biological and immunological data (NCT03751683). RESULTS: 25 patients (23 families) were enrolled. Eleven distinct AIRE variants were identified, two of which were not previously reported: an intronic variant, c.653-70G > A, and a c.1066del (p.Arg356GlyfsX22) variant (exon 9). The most common was the Finnish variant c.769C > T (16 alleles), followed by the variant c.967_979del13 (15 alleles), which seemed associated with a less severe phenotype. 17/25 patients were homozygote. The median number of clinical manifestations was seven; 19/25 patients presented with the hypoparathyroidism-adrenal failure-CMC triad, 8/13 showed pulmonary involvement, 20/25 had ectodermal dystrophy, 8/25 had malabsorption, and 6/23 had asplenia. Fifteen out of 19 patients had NK cell lymphopenia with an increase in CD4+ and CD8+ T lymphocytes and an age-dependent alteration of B lymphocyte homeostasis compared with matched controls (p < 0.001), related to the severity of the disease. All tested sera (n = 18) were positive for anti-interferon-α, 15/18 for anti-interleukin-22 antibodies, and 13/18 for anti-interleukin-17F antibodies, without clear phenotypic correlation other than with CMC. CONCLUSION: This first prospective cohort showed a high AIRE genotype variability, with two new gene variants. The prevalence of potentially life-threatening non-endocrine manifestations, was higher with systematic screening. These manifestations could, along with age-dependent B-cell lymphopenia, contribute to disease severity. Systematic screening for all the manifestations of the syndrome would allow earlier diagnosis, supporting vaccination, and targeted therapeutic approaches.
RESUMO
EXPLORATION AND MANAGEMENT OF THYROID NODULES. Most thyroid nodules are benign (95%) and can benefit from clinical and ultrasound monitoring. Cancers (approximately 5% of nodules) could be suspected, particularly in subjects whose neck was irradiated, in cases of a hard, irregular, evolving nodule, or with very high serum calcitonin (> 100 pg/ml). It is crucial to recognize cancers when nodules exceed the supracentimeter stage. Thyroid ultrasonography is the most common, handy, safe, and cost-effective tool to image thyroid nodules. It classifies thyroid nodules according to the EU-TIRADS score, which comprises 5 categories associated with an increasing risk of malignancy. An ultrasound-guided fine needle aspiration (FNA) biopsy is performed only in nodules staged EU-TIRADS classes 5, 4, and 3 over 1, 1.5, and 2 cm, respectively. Cytologic analysis of FNA material classifies thyroid nodules according to the Bethesda system into 6 classes, each with its own prognostic value. The difficulties in cytological evaluation are related to the uninterpretable (Bethesda I) and indeterminate (especially III and IV) results, for which have to be discussed opportunities of reassessment and follow-up by scintiscans and cytological molecular markers. Management is imperfectly codifiable: from surveillance in the absence of suspicious elements initially to total thyroidectomy in their presence.
EXPLORATION ET PRISE EN CHARGE DES NODULES THYROÏDIENS. La plupart des nodules thyroïdiens sont bénins (95 %) et peuvent bénéficier d'une surveillance clinique et échographique. La malignité (5 % des nodules environ) est à suspecter, particulièrement chez les sujets dont le cou a été irradié, en cas de nodule dur, irrégulier, évolutif, avec une calcitoninémie très élevée (supérieure à 100 pg/mL). C'est au stade de nodule supracentimétrique qu'il importe de reconnaître les cancers. L'échographie est l'examen d'imagerie de référence ; elle permet de classer les nodules selon le score EU-TIRADS, composé de cinq catégories associées à un risque croissant de malignité. Les ponctions échoguidées en vue de l'analyse cytologique sont réservées aux catégories EU-TIRADS 5, 4 et 3 de plus de 1, 1,5 et 2 cm respectivement. Les caractéristiques cytologiques sont présentées selon la nomenclature de Bethesda en six classes dont chacune quantifie aussi le risque de malignité, en complément des données échographiques. Les difficultés de l'évaluation cytologique sont liées aux résultats ininterprétables (Bethesda I) et indéterminés (surtout Bethesda III et IV) pour lesquels se discutent l'opportunité de la réévaluation et de la surveillance, des scintigraphies dites de seconde intention, et également des marqueurs moléculaires sur le produit de cytoponction. La prise en charge est imparfaitement codifiable : de la surveillance en l'absence d'éléments suspects initialement à la thyroïdectomie totale en leur présence.
Assuntos
Neoplasias da Glândula Tireoide , Nódulo da Glândula Tireoide , Humanos , Nódulo da Glândula Tireoide/diagnóstico , Nódulo da Glândula Tireoide/terapia , Nódulo da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/patologia , Estudos Retrospectivos , Ultrassonografia , Biópsia por Agulha Fina/métodosRESUMO
Introduction: Reprogramming of cellular metabolism is now a hallmark of tumorigenesis. In recent years, research on pancreatic neuroendocrine tumors (pNETs) has focused on genetic and epigenetic modifications and related signaling pathways, but few studies have been devoted to characterizing the metabolic profile of these tumors. In this review, we thoroughly investigate the metabolic pathways in pNETs by analyzing the transcriptomic and metabolomic data available in the literature. Methodology: We retrieved and downloaded gene expression profiles from all publicly available gene set enrichments (GSE43797, GSE73338, and GSE117851) to compare the differences in expressed genes based on both the stage and MEN1 mutational status. In addition, we conducted a systematic review of metabolomic data in NETs. Results: By combining transcriptomic and metabolomic approaches, we have identified a distinctive metabolism in pNETs compared with controls without pNETs. Our analysis showed dysregulations in the one-carbon, glutathione, and polyamine metabolisms, fatty acid biosynthesis, and branched-chain amino acid catabolism, which supply the tricarboxylic acid cycle. These targets are implicated in pNET cell proliferation and metastasis and could also have a prognostic impact. When analyzing the profiles of patients with or without metastasis, or with or without MEN1 mutation, we observed only a few differences due to the scarcity of published clinical data in the existing research. Consequently, further studies are now necessary to validate our data and investigate these potential targets as biomarkers or therapeutic solutions, with a specific focus on pNETs.
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Tumores Neuroectodérmicos Primitivos , Tumores Neuroendócrinos , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/patologia , Tumores Neuroendócrinos/patologia , Prognóstico , Epigênese Genética , Tumores Neuroectodérmicos Primitivos/genéticaRESUMO
Introduction: Anaplastic thyroid carcinoma (ATC) is the most aggressive form of thyroid cancer with a bleak prognosis. Favorable outcomes are rare but help decipher molecular pathophysiology, investigate prognosis factors, and discover new therapeutic targets. Case presentation: Two patients were diagnosed with locally advanced nonresectable ATC, one with metastatic extension. Each patient received chemotherapy and radiotherapy, allowing thyroid surgical resection. In both cases, the pathological examination was consistent with complete response with no viable tumor cells. After follow-ups of 48 and 70 months, both patients remain disease-free. Molecular explorations on thyroid biopsies revealed microsatellite instability (MSI) and alterations on mismatch repair-gene complex, also PTEN and ATM variants in both cases. Both also presented with non-classical immune infiltrate composed of equal parts T CD4+ lymphocytes and macrophages. Conclusion: We report two cases of patients cured from advanced ATC and for the first time provide genetic and immunological explorations in this setting. It seems with these two cases that MSI-ATCs may indicate a better prognosis. Our study hypothesizes different responsible mechanisms including increased sensitivity to chemoradiotherapy and/or immune tumor infiltrate modulation.
Assuntos
Radioterapia (Especialidade) , Carcinoma Anaplásico da Tireoide , Neoplasias da Glândula Tireoide , Humanos , Carcinoma Anaplásico da Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/tratamento farmacológico , PrognósticoRESUMO
OBJECTIVE: Glucagonoma is a very rare functional pancreatic neuroendocrine tumor (PanNET). We aimed to provide data on the diagnosis, prognosis, and management of patients with glucagonoma. DESIGN AND METHODS: In this retrospective national cohort, we included all patients with glucagonoma, defined by at least 1 major criterion (necrolytic migratory erythema [NME] and/or recent-onset diabetes, and/or weight loss ≥ 5â kg) associated with either glucagonemia > 2 × upper limit of normal or positive glucagon immunostaining. Antisecretory efficacy was defined as partial/complete resolution of glucagonoma symptoms. Antitumor efficacy was assessed according to the time to next treatment (TTNT). RESULTS: Thirty-eight patients were included with median age 58.7 yo, primary PanNET located in the tail (68.4%), synchronous metastases (63.2%). Median Ki-67 index was 3%. Most frequent glucagonoma symptoms at diagnosis were NME (86.8%), weight loss (68.4%), and diabetes (50%). Surgery of the primary PanNET was performed in 76.3% of cases, mainly with curative intent (61.5%). After surgery, complete resolution of NME was seen in 93.8% (n = 15/16). The secretory response rates were 85.7%, 85.7%, 75%, and 60% with surgery of metastases (n = 6/7), chemotherapy (n = 6/7), liver-directed therapy (n = 6/8), and somatostatin analogs (n = 6/10), respectively. All lines combined, longer TTNT was reported with chemotherapy (20.2 months). Median overall survival (OS) was 17.3 years. The Ki-67 index > 3% was associated with shorter OS (hazard ratio 5.27, 95% CI [1.11-24.96], P = .036). CONCLUSION: Patients with glucagonoma had prolonged survival, even in the presence of metastases at diagnosis. Curative-intent surgery should always be considered. Chemotherapy, peptide receptor radionuclide therapy, or liver-directed therapy seems to provide both substantial antitumor and antisecretory efficacies.