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Carcinoma Papilar , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide , Tireoidectomia , Humanos , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/cirurgia , Carcinoma Papilar/patologia , Câncer Papilífero da Tireoide/patologia , Japão , Carcinoma/patologia , Medição de Risco , Resultado do Tratamento , População do Leste AsiáticoRESUMO
CONTEXT: Primary hyperparathyroidism (PHPT) is an endocrine disorder that is treated surgically, and some correlation between the size of the responsible lesion and preoperative clinical data is assumed. The purpose of this study was to predict tumor volume of the lesion responsible for PHPT from preoperative clinical data. METHODS: Participants comprised patients with surgically treated PHPT who underwent initial surgery in our department between January 2000 and December 2021. The volume of parathyroid gland removed was used as the primary outcome and associations with preoperative clinical data were assessed by multivariable analysis. RESULTS: A positive correlation was identified between parathyroid tumor volume and both preoperative intact parathyroid hormone (PTH) (Spearman's r = 0.503) and calcium values (Spearman's r = 0.338). Data for intact PTH value and tumor volume were logarithmically transformed (ln-PTH = log-transformed intact PTH value; ln-volume = log-transformed tumor volume). Multiple regression analysis revealed male sex, ln-PTH and calcium values as significant predictors of ln-volume, with standardized regression coefficients of 0.213 (95% confidence interval [CI] 0.103-0.323), 0.5018 (95%CI 0.4442-0559) and 0.322 (95%CI 0.0339-0.149), respectively. The adjusted R2 for this model is 0.320. CONCLUSIONS: Preoperative serum intact PTH value is associated with tumor volume of the lesion responsible for PHPT. A rough estimation of the tumor size would provide responsible physicians with opportunities to add further imaging tests or plan appropriate surgical strategies.
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In papillary thyroid carcinoma (PTC) patients with mediastinal lymph nodes (LN) and lung metastases, adding preoperative computed tomography (CT) to ultrasound is useful for planning surgery. We identified risk factors (RFs) for mediastinal lymph node metastasis (MLNM) and lung metastasis in PTC patients. Frequencies of MLNM and lung metastases were compared in 478 patients. Relative risk (RR) was calculated based on RFs. MLNM and lung metastases were detected in 1.2% and 3.3% of patients, respectively. cT3-4, cN1, central LN metastasis, and lateral LN metastasis were RFs for MLNM in all patients (p < 0.05, p < 0.05, p < 0.05, p < 0.01) and older patients (age: ≥55 years) (p < 0.01, p < 0.05, p < 0.05, p < 0.05). cT3-4, cN1, gross extrathyroidal extension, central LN metastasis, and lateral LN metastasis were RFs for lung metastasis in all patients (p < 0.01, p < 0.05, p < 0.01, p < 0.01, p < 0.01, respectively). cN1 and gross extrathyroidal extension, central LN metastasis, and lateral LN metastasis were RFs in older patients (p < 0.01, p < 0.01, p < 0.05, p < 0.01), while lateral LN metastasis was an RF for lung metastasis in those of <55 years of age (younger patients) (p < 0.05). No MLNM was observed in cT1-2cN0 PTC patients, who accounted for 50.5% of patients included in the MLNM analysis. No lung metastasis was present in cT1-2cN0 PTC patients, who accounted for 50.5% of the patients included in the lung metastasis analysis. PTC patients with cT3-4 and cN1 have an increased risk of MLNM and lung metastasis. RFs differed between older and younger patients. Preoperative neck and chest CT are not necessary for PTC patients with ultrasound-diagnosed as cT1-2cN0.
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Neoplasias Pulmonares , Metástase Linfática , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide , Tomografia Computadorizada por Raios X , Humanos , Pessoa de Meia-Idade , Masculino , Feminino , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/secundário , Metástase Linfática/diagnóstico por imagem , Adulto , Câncer Papilífero da Tireoide/patologia , Câncer Papilífero da Tireoide/diagnóstico por imagem , Câncer Papilífero da Tireoide/secundário , Fatores de Risco , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Idoso , Mediastino/diagnóstico por imagem , Linfonodos/patologia , Linfonodos/diagnóstico por imagem , Adulto Jovem , Cuidados Pré-Operatórios , Adolescente , Estudos Retrospectivos , TireoidectomiaRESUMO
The prevalence of adrenal incidentaloma (AI) in imaging studies, including those of the adrenal glands, is estimated to be 1-5%. Essential factors for the proper management of AI include a correct diagnosis, adequate surgical skills, appropriate perioperative management, and sound dialogue with the patient. Aside from the possibility of overdiagnosis, patients with apparent signs or symptoms attributable to adrenal hormone excess have reasonable indications for surgery. At the same time, milder patients may be candidates for active surveillance without intervention. Even individuals with nonfunctioning AI may benefit from surgery if imaging studies depict the tumor as suggestive of malignancy. However, a differential diagnosis of AI may not be easy for surgeons with little experience in seeing such patients.Furthermore, a patient without a correct diagnosis may miss the window of opportunity for a cure or incur a greater risk of developing complications, such as adrenal insufficiency or cardiovascular events during or after surgery, due to inadequate management. The clinical practice guidelines for AI from around the world may be helpful for shared decision-making; however, Japan lacks established guidelines. In this review article, we propose practical guidelines relevant to management by summarizing the evidence for five key questions that are often asked in dialog with patients with AI.
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BACKGROUND: The management of intermediate-risk group of papillary thyroid cancer (PTC) is still vague, particularly regarding whether or not total thyroidectomy, postoperative radioactive iodine ablation (RAI-a), and postoperative TSH suppression are mandatory. METHODS: This retrospective study evaluated 680 PTC patients from 2010 to 2017, who were classified into the three risk groups as low, intermediate, and high-risk groups according to the criteria of the Japanese Association of Endocrine Surgeons (JAES) 2010 and underwent surgery according to the JAES guidelines. We retrospectively collected patient data for analyses of disease-free survivals in the intermediate-risk group patients. RESULTS: We performed surgery on 680 PTC patients from 2010 to 2017. Of them, 297 were classified as the intermediate-risk group. DFS was not statistically significantly different in patients with/without total thyroidectomy and postoperative TSH suppression therapy. For RAI-a, DFS (95% confidence interval) at 3, 5, and 8 years were 93.2% (84.6 ~ 97.2), 81.6% (68,3 ~ 90.2), and 70.7% (51.4 ~ 84.6) in patients with postoperative RAI-a and 100%, 100%, and 100% in patients without postoperative RAI-a after total thyroidectomy, respectively. DFS of patients without RAI-a was superior to those with RAI-a (P < 0.0004). Multivariable analysis by stepwise selection method revealed that postoperative RAI-a was a risk factor with a hazard ratio of 5.69. (95% CI 1.998-16.21) (P = 0.001131). CONCLUSIONS: Our study did not show the efficacy of RAI-a in patients with intermediate-risk PTC. This study implies that judging the efficacy of adjuvant therapy such as RAI or TSh suppression in intermediate-risk patients is difficult.
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Carcinoma Papilar , Iodo , Neoplasias da Glândula Tireoide , Humanos , Câncer Papilífero da Tireoide/cirurgia , Neoplasias da Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/patologia , Estudos Retrospectivos , Radioisótopos do Iodo , População do Leste Asiático , Carcinoma Papilar/cirurgia , Carcinoma Papilar/patologia , Fatores de Risco , Tireoidectomia , TireotropinaRESUMO
BACKGROUND: Distant metastasis is extremely rare for papillary thyroid microcarcinoma (PTMC) without lymph node metastasis or extrathyroidal extension, for which active surveillance (AS) is indicated. The evaluation of distant metastases in low-risk PTMC is controversial. A case of PTMC in which AS would have been performed if chest CT and lung surgery had not been performed is reported. CASE PRESENTATION: The patient was a 71-year-old woman undergoing follow-up in the Department of Thoracic Surgery at our hospital for multiple frosted glass shadows in both lung fields for one and a half years. To make a definitive diagnosis, thoracoscopic right middle lobectomy and left upper partial lobectomy were performed 4 and 6 months earlier, respectively. In both resected specimens, lung adenocarcinoma and small metastasis of papillary thyroid carcinoma (PTC) were found. The patient was transferred to our department for a thorough examination for PTC. Ultrasonography was performed to search for the primary lesion, and it showed an irregular hypoechoic mass of 4 mm and 6 mm in the middle of the right lobe of the thyroid gland. The patient was diagnosed with PTC. Its clinical stage was T1a (m) N0 M1 (stage IVC). Total thyroidectomy and prophylactic central node dissection were performed. The pathological diagnosis was PTC (typical type) pT1a (m) N0. Postoperatively, she received radioactive iodine therapy. CONCLUSIONS: We experienced an extremely rare case and struggled to determine a treatment plan. We might be aware that lung metastases could develop in low-risk PTMC.
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INTRODUCTION: Non-total thyroidectomy (non-TTx) is a widely accepted operative procedure for low-risk papillary thyroid carcinoma (PTC). PTC patients preoperatively diagnosed with unifocal disease are often revealed as having multifocal foci by microscopy. The present study determined whether or not patients with clinically unifocal, but pathologically multifocal non-high-risk PTC treated with non-TTx have an increased risk of a poor prognosis compared to those with pathologically unifocal PTC. MATERIALS AND METHODS: PTC patients diagnosed as unifocal preoperatively who underwent non-TTx were multifocal in 61 and unifocal in 266 patients microscopically. Oncologic event rates were compared between pathologically multifocal and unifocal PTC patients. RESULTS: Pathological multifocality was associated with positive clinical lymph node metastasis (cN1) (odds ratio [OR] 4.01, 95% confidence interval [CI]: 1.91-8.04) and positive pathological lymph node metastasis (pN1) in > 5 nodes (OR 3.68, 95% CI: 1.60-8.49). No patients died from PTC. There was no significant difference in the disease-free survival rate, remnant thyroid disease-free survival rate, lymph node disease-free survival rate, or distant disease-free survival rate between the two groups. Recurrence in pathologically multifocal PTC patients was locoregional in all cases and able to be salvaged by reoperation. Cox proportional hazard model analyses showed no significant difference in recurrence rates with regard to pathological multifocality and cN or number of pNs. CONCLUSION: The prognosis of PTC with pathological multifocality treated by non-TTx was not inferior to that of unifocal PTC. Immediate completion thyroidectomy is not necessary when microscopic foci are proven.
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Carcinoma Papilar , Neoplasias da Glândula Tireoide , Humanos , Câncer Papilífero da Tireoide/cirurgia , Metástase Linfática , Estudos Retrospectivos , Carcinoma Papilar/patologia , Neoplasias da Glândula Tireoide/patologia , Tireoidectomia , Prognóstico , Fatores de Risco , Recidiva Local de Neoplasia/cirurgia , Recidiva Local de Neoplasia/patologiaRESUMO
BACKGROUND: This study aimed to identify the predictive value of the extent of metastatic lymph nodes in the central and lateral neck compartment for recurrence in papillary thyroid cancer (PTC) patients with pathologically lateral lymph node metastasis (pN1b). METHODS: This study enrolled 252 patients with pN1b from PTC. RESULTS: During a mean follow-up of 17.6 years, 55 (21.8%) patients experienced recurrence. Patients with palpable lymph nodes were more likely to have a recurrence than those with nonpalpable lymph nodes (30.1% vs. 17.8%, relative risk 1.7, 95%CI: 1.1-2.7). For patients with palpable metastatic lymph nodes, lymph node ratio of lateral lymph nodes ≥0.5 (aHR = 2.906, 95%CI: 1.29-6.54) and age ≥55 years (aHR = 2.508, 95%CI: 1.12-5.63) were independent prognostic factors. For those without palpable nodes, age ≥55 years (aHR = 2.224, 95%CI: 1.08-4.60) and tumor size >4 cm (aHR = 2.168, 95%CI: 1.01-4.66) were independently predictive of worse RFS. CONCLUSIONS: Palpable lymph nodes were approximately twice as likely to recur as nonpalpable nodes. Metastatic lateral lymph node ratio predicts recurrence in pN1b PTC patients with palpable lymph nodes, but not those without ones.
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Carcinoma Papilar , Neoplasias da Glândula Tireoide , Carcinoma Papilar/patologia , Humanos , Razão entre Linfonodos , Linfonodos/patologia , Pessoa de Meia-Idade , Esvaziamento Cervical , Recidiva Local de Neoplasia/patologia , Estudos Retrospectivos , Câncer Papilífero da Tireoide/patologia , Câncer Papilífero da Tireoide/cirurgia , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/cirurgia , TireoidectomiaRESUMO
BACKGROUND: Cancer-related fatigue is one of the most important issues for patients, but research on this topic is sparse. This study aimed to determine the prevalence of fatigue in postoperative patients with papillary thyroid carcinoma (PTC) and to identify the clinical features associated with fatigue. METHODS: We conducted a cross-sectional study on 292 thyroid cancer survivors. Fatigue and quality of life were the study outcomes, measured using the Cancer Fatigue Scale (CFS) and the SF-36 version 2.0. Furthermore, correlations of demographic characteristics and hormonal data with the CFS scores were assessed by univariable and multivariable analyses. RESULTS: The prevalence of fatigue was 41.8% (95% CI: 36.1, 47.5). The CFS score was significantly correlated with the free T3 level (Pearson's r = -0.123, 95% CI: -0.234, -0.008). Multiple regression analysis revealed that the free T3 level and having a job were significant predictors of the CFS score, with unstandardized regression coefficients of -2.52 (95% CI: -4.94, -0.09) and 2.85 (95% CI: 0.49, 5.20), respectively. The median Z-scores were negative for General Health (-0.28) and Vitality (-0.15) subscales of the SF-36. The CFS score was a significant predictor of summary scores of the SF-36. The free T3 level was significantly associated with the physical component summary score with an unstandardized coefficient of 3.20 (95% CI: 0.77, 5.63). CONCLUSIONS: Fatigue was prevalent and associated with poor quality of life among PTC survivors. Thyroid functional status, particularly the level of free T3, may be worth to be considered in alleviating the burden.
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Neuroendocrine neoplasms (NENs) are rare neoplasms that occur in various organs and present with diverse clinical manifestations. Pathological classification is important in the diagnosis of NENs. Treatment strategies must be selected according to the status of differentiation and malignancy by accurately determining whether the neoplasm is functioning or nonfunctioning, degree of disease progression, and presence of metastasis. The newly revised Clinical Practice Guidelines for Gastroenteropancreatic Neuroendocrine Neoplasms (GEP-NENs) comprises 5 chapters-diagnosis, pathology, surgical treatment, medical and multidisciplinary treatment, and multiple endocrine neoplasia type 1 (MEN1)/von Hippel-Lindau (VHL) disease-and includes 51 clinical questions and 19 columns. These guidelines aim to provide direction and practical clinical content for the management of GEP-NEN preferentially based on clinically useful reports. These revised guidelines also refer to the new concept of "neuroendocrine tumor" (NET) grade 3, which is based on the 2017 and 2019 WHO criteria; this includes health insurance coverage of somatostatin receptor scintigraphy for NEN, everolimus for lung and gastrointestinal NET, and lanreotide for GEP-NET. The guidelines also newly refer to the diagnosis, treatment, and surveillance of NEN associated with VHL disease and MEN1. The accuracy of these guidelines has been improved by examining and adopting new evidence obtained after the first edition was published.
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Guias como Assunto , Neoplasias Intestinais/diagnóstico , Neoplasias Intestinais/terapia , Tumores Neuroendócrinos/diagnóstico , Tumores Neuroendócrinos/terapia , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/terapia , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/terapia , Assistência ao Convalescente/métodos , Assistência ao Convalescente/tendências , Humanos , Neoplasias Intestinais/fisiopatologia , Tumores Neuroendócrinos/fisiopatologia , Neoplasias Pancreáticas/fisiopatologia , Neoplasias Gástricas/fisiopatologiaRESUMO
We have a unique history of using radioactive iodine (RAI) therapy and surgical treatment for thyroid cancer in Japan. Less than total thyroidectomy without RAI therapy was the most common management of papillary thyroid carcinoma (PTC) in the past. Limited availability of dedicated facilities for the RAI administration due to the strict regulations and insufficient coverage of the expenses were the major reasons that impacted on the management decisions. Following the publication of the Japanese clinical practice guidelines for thyroid tumors in 2010, the risk-adapted approach has become a standard where the high-risk and selected intermediate-risk PTC patients undergo total thyroidectomy followed by RAI therapy and thyrotropin suppression therapy. We are on the shoulders of pioneers who made every effort to bring the interventions closer to an ideal environment for patients. Armed with the revised clinical practice guidelines 2018 and devised inpatient/outpatient RAI therapy, Japanese physicians are ready to proceed to more rational management that would improve patients' outcomes. Directions for the future include further advancement of relevant clinical research to fill the gaps between current evidence and recommendations in the guidelines, and obtaining approval for high-dose RAI therapy on an outpatient basis to improve its effectiveness in both adjuvant and treatment settings.
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OBJECTIVE: Multiple endocrine neoplasia type 2A (MEN 2A) is a rare syndrome caused by RET germline mutations and has been associated with primary hyperparathyroidism (PHPT) in up to 30% of cases. Recommendations on RET screening in patients with apparently sporadic PHPT are unclear. We aimed to estimate the prevalence of cases presenting with PHPT as first manifestation among MEN 2A index cases and to characterize the former cases. DESIGN AND METHODS: An international retrospective multicenter study of 1085 MEN 2A index cases. Experts from MEN 2 centers all over the world were invited to participate. A total of 19 centers in 17 different countries provided registry data of index cases followed from 1974 to 2017. RESULTS: Ten cases presented with PHPT as their first manifestation of MEN 2A, yielding a prevalence of 0.9% (95% CI: 0.4-1.6). 9/10 cases were diagnosed with medullary thyroid carcinoma (MTC) in relation to parathyroid surgery and 1/10 was diagnosed 15 years after parathyroid surgery. 7/9 cases with full TNM data were node-positive at MTC diagnosis. CONCLUSIONS: Our data suggest that the prevalence of MEN 2A index cases that present with PHPT as their first manifestation is very low. The majority of index cases presenting with PHPT as first manifestation have synchronous MTC and are often node-positive. Thus, our observations suggest that not performing RET mutation analysis in patients with apparently sporadic PHPT would result in an extremely low false-negative rate, if no other MEN 2A component, specifically MTC, are found during work-up or resection of PHPT.
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Background: Clinical practice guidelines have endorsed both active surveillance and surgery as viable management options for papillary thyroid microcarcinoma (PTMC). However, patients' perceptions on the options have rarely been addressed. Methods: A cross-sectional survey was conducted on 50 patients with PTMC who were under either active surveillance (n = 20) or postoperative follow-up (n = 30). The primary outcome was anxiety, which was measured using the State-Trait Anxiety Inventory (STAI). A questionnaire that comprised six items about PTMC-related symptoms and concerns, which were measured with a visual analog scale, was also administered. Cohen's d effect size was calculated to express group differences. Multiple regression analysis was used to examine the relationships between state anxiety and other variables. Results: The median age and observation period were 61.5 years (range, 40-83 years) and 4.1 years (range, 0-8.6 years), respectively. The female/male ratio was 38/12. Compared with the surgery group, the active surveillance group showed higher scores in both state anxiety and trait anxiety, with corresponding effect sizes of 0.55 (confidence interval [CI] -0.03 to 1.1; p = 0.068) and 0.63 (CI 0.02-1.2; p = 0.037), respectively. Trait anxiety (ß = 0.83) and observation time (ß = -1.57) were the significant predictors of state anxiety. Moderate effect sizes were observed for "discomfort in the neck" (-0.53; CI -1.11 to 0.04); "weak voice" (-0.46; CI -1.03 to 0.12); and "nervous about neck appearance" (-0.64; CI -1.23 to -0.07), in favor of active surveillance. Conclusions: State anxiety among patients with PTMC seemed to be a reflection of an individual's trait rather than management. Understanding the patients' view appears to be key to improve shared decision-making.
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Câncer Papilífero da Tireoide/terapia , Neoplasias da Glândula Tireoide/terapia , Tireoidectomia , Conduta Expectante , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Inquéritos e Questionários , Câncer Papilífero da Tireoide/patologia , Câncer Papilífero da Tireoide/cirurgia , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/cirurgiaRESUMO
PURPOSE: To establish if parathyroidectomy is beneficial for patient-reported outcomes (PROs), including quality of life (QoL), of patients with mild hypercalcemia ( < 1.0 mg/dl above the upper limit of reference ranges) caused by primary hyperparathyroidism without classic symptoms (mild PHPT). METHODS: We conducted a systematic review of the literature. Prospective studies were selected if PROs were measured before and after surgery and if the subpopulation of mild PHPT was clearly defined. Selected studies were appraised for their designs, PRO measures, and potential biases, as well as findings. Effect sizes were estimated to evaluate the extent of the benefits, if possible. RESULTS: Four randomized controlled trials and six observational studies were included in this analysis. Seven studies used the SF-36 to measure QoL and the other three used different scales. Quantitative data on outcomes were provided in the four observational studies, but effect sizes could not be estimated. A placebo effect of surgery was discussed in five studies. Statistically significant improvements in PROs were observed in all studies, but the clinical importance of the changes was not discussed in detail. CONCLUSIONS: The surgical treatment of mild PHPT may be associated with improved PROs, but the clinical significance of the changes is not yet confirmed.
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Hipercalcemia/etiologia , Hiperparatireoidismo/complicações , Hiperparatireoidismo/cirurgia , Medidas de Resultados Relatados pelo Paciente , Doenças Assintomáticas , Humanos , Estudos Prospectivos , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
OBJECTIVE: The efficacy of low-dose radioiodine therapy (RIT) for intermediate-risk or high-risk differentiated thyroid cancer (DTC) patients is controversial. Because of the country's shortage of medical facilities for RIT, 1110-MBq RIT for higher risk DTC patients has been performed on an outpatient basis since 2010 in Japan. Herein, we addressed this issue and attempted to determine prognostic factors for the prediction of RIT outcomes. METHODS: We retrospectively analyzed the cases of 119 patients with papillary thyroid cancer who underwent their first RIT with 1110 MBq radioactive iodine (RAI) following a total thyroidectomy, including 65 (54.6%) intermediate-risk and 54 (45.4%) high-risk patients (according to Japan's 2018 clinical practical guidelines for thyroid tumors). Successful ablation was defined when a negative I-131 whole-body scan and thyroglobulin (Tg) < 2 ng/mL were obtained at a diagnostic scan performed 148-560 days (median 261 days) after the first RIT. RESULTS: The overall ablation success rate was 23.4%. Although the ablation success rates of each pretreatment protocol [recombinant human thyroid stimulating hormone and thyroid hormone withdrawal (THW)] did not differ significantly, THW tended to result in a higher success rate than rhTSH. The Tg level at RIT was the only independent powerful predictive factor for successful ablation. The best cut-off value of Tg for predicting unsuccessful ablation was 9 ng/mL. CONCLUSIONS: The ablation success rate was much lower than those of earlier studies; the most plausible reason would be that higher risk DTC patients were included in this study. The low-dose RIT routinely performed in Japan might be inadequate for the achievement of successful ablation. At least for patients with Tg > 9 ng/mL at the first RIT, a higher dose of RAI is recommended.
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Antineoplásicos/farmacologia , Radioisótopos do Iodo/farmacologia , Câncer Papilífero da Tireoide/radioterapia , Neoplasias da Glândula Tireoide/radioterapia , Adulto , Idoso , Relação Dose-Resposta à Radiação , Feminino , Seguimentos , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de Risco , Tireoglobulina/metabolismo , Tireoidectomia , Tirotropina Alfa/metabolismo , Fatores de Tempo , Resultado do Tratamento , Imagem Corporal TotalRESUMO
Background: Little is known about annual hazard rates of cancer mortality and recurrence for papillary thyroid cancer (PTC). This study investigated the time-varying pattern of cancer death and recurrence from PTC and independent prognostic factors for cause-specific mortality (CSM) and recurrence of PTC. Methods: This retrospective chart review enrolled 466 patients diagnosed with PTC who underwent curative initial surgery between April 1981 and December 1991 with a median follow-up of 18.4 years. Clinical characteristics, cancer mortality (primary endpoint), and recurrence (secondary endpoint) were ascertained. The failure rates of either death or recurrence were estimated using the Kaplan-Meier methods, and annual death/recurrence hazard was depicted using hazard function. Results: In this Japanese cohort where only 1.5% of patients received radioactive iodine therapy, the 10-, 20-, and 30-year CSM rates were 2.7%, 6.2%, and 8.6%, respectively. Eleven (44.0%) cases of death occurred within the first 10 years, whereas 10 (40.0%) and 4 (16.0%) cases occurred within 10-20 and 20-30 years after surgery, respectively. The 10-, 20-, and 30-year recurrence rates were 11.3%, 21.8%, and 29.4%, respectively. Forty-six (54.8%) cases of recurrence occurred within the first 10 years, predominantly within the first five years (31 cases; 36.9%), whereas 29 (34.5%), 7 (8.3%), and 2 (2.4%) cases occurred within 10-20, 20-30, and ≥30 years after surgery, respectively. Age ≥55 years was the only independent prognostic factor for CSM. Age ≥55 years, male, tumor size > 4 cm, extranodal extension, and positive pathological lymph node metastasis were independent prognostic factors for recurrence. The annual hazard curve of cancer mortality presented a double-peaked distribution, with a first peak at the 10th year, and the second peak reaching the maximum at the 20th year after surgery for the entire population. The annual hazard curve of recurrence showed a triple-peaked pattern, with surges at about 12, 22, and 29 years after surgery. Conclusions: Patients with PTC harboring at least one of the prognostic characteristics may be at persistent risk of cancer mortality and recurrence even 10 or more years after initial treatment. Understanding the hazard rate of PTC is key to creating more tailored treatment and surveillance.
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Recidiva Local de Neoplasia/mortalidade , Câncer Papilífero da Tireoide/mortalidade , Neoplasias da Glândula Tireoide/mortalidade , Adulto , Fatores Etários , Idoso , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Prognóstico , Estudos Retrospectivos , Fatores Sexuais , Taxa de Sobrevida , Câncer Papilífero da Tireoide/patologia , Neoplasias da Glândula Tireoide/patologia , Fatores de TempoRESUMO
Primary hyperparathyroidism is the most common hormonal manifestation associated with multiple endocrine neoplasia 1 (MEN1). It is generally caused by parathyroid hyperplasia, and parathyroid carcinoma is rare. Here, we report a case of MEN1 with parathyroid carcinoma in two parathyroid glands causing primary hyperparathyroidism. A 40-year-old man with primary hyperparathyroidism due to MEN1 underwent a total parathyroidectomy. His corrected calcium and intact PTH (i-PTH) serum levels were 10.8 mg/dL and 203 pg/mL, respectively. Although three glands were successfully removed, the left upper parathyroid gland could not be detected. Since the right lower parathyroid lesion had invaded into the thyroid, right lobectomy was performed. A portion of the left lower parathyroid tissue was transplanted into his forearm. The histological findings of the left lower and the right upper parathyroid glands were consistent with hyperplasia while that of the right lower parathyroid gland was parathyroid carcinoma. Since the post-surgical i-PTH levels remained high, the intrathyroidal lesion of the left lobe, which was initally diagnosed as an adenomatous nodule, was suspected to contain parathyroid tumor. A fine needle aspiration of the tumor revealed a high concentration of i-PTH. One week after the first surgery, a left thyroid lobectomy was performed. The pathological diagnosis of the tumor was parathyroid carcinoma. After the surgery, calcium and i-PTH levels were normal. Although it is rare, parathyroid carcinoma should be considered as a cause of hyperparathyroidism in MEN1 patients. Since it is difficult to diagnose parathyroid carcinoma before surgery, intraoperative findings are important for the appropriate treatment.
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Coristoma/diagnóstico , Hiperparatireoidismo Primário/diagnóstico , Neoplasia Endócrina Múltipla Tipo 1/diagnóstico , Síndromes Endócrinas Paraneoplásicas/diagnóstico , Glândulas Paratireoides , Neoplasias das Paratireoides/diagnóstico , Neoplasias da Glândula Tireoide/diagnóstico , Adulto , Coristoma/complicações , Coristoma/metabolismo , Humanos , Hiperparatireoidismo Primário/etiologia , Masculino , Neoplasia Endócrina Múltipla Tipo 1/complicações , Neoplasia Endócrina Múltipla Tipo 1/patologia , Neoplasias Primárias Múltiplas/diagnóstico , Neoplasias Primárias Múltiplas/metabolismo , Neoplasias Primárias Múltiplas/patologia , Neoplasias Pancreáticas/complicações , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/patologia , Síndromes Endócrinas Paraneoplásicas/complicações , Síndromes Endócrinas Paraneoplásicas/metabolismo , Hormônio Paratireóideo/metabolismo , Neoplasias das Paratireoides/patologia , Neoplasias da Glândula Tireoide/metabolismo , Neoplasias da Glândula Tireoide/secundárioRESUMO
BACKGROUND: Whether total parathyroidectomy (TPTX) or subtotal parathyroidectomy (SPTX) should be performed for primary hyperparathyroidism (PHPT) in patients with multiple endocrine neoplasia type 1 (MEN1) is controversial. At our institution, the parathyroidectomy strategy is based on the number of enlarged intraoperative parathyroid glands. We retrospectively analyzed our parathyroidectomy procedures. METHODS: Data of PHPT treatment in patients with MEN1 who underwent parathyroidectomy from 1982 to 2012 at our department were retrospectively collected. The data were grouped according to the surgical procedure: TPTX, SPTX, and less than SPTX (LPTX). TPTX or SPTX was selected based on the preoperative examination findings and number of enlarged intraoperative parathyroid glands. The outcomes were the disease-free survival (DFS) rate and postoperative calcium replacement rate based on Kaplan-Meier analysis for each type of surgical procedure. RESULTS: Forty-five patients were analyzed. The overall 5- and 10-year DFS was 91.7 and 55.8%, respectively. The 5- and 10-year DFS in each subgroup was 100.0 and 85.7% in the TPTX group, 89.4 and 57.3% in the SPTX group, and 91.6 and 57.3% in the LPTX group, respectively. The postoperative calcium replacement rate at 1 and 12 months was 91.7 and 58.3% in the TPTX group, 21.1 and 7.0% in the SPTX group, and 30.0 and 0.0% in the LPTX group, respectively. CONCLUSIONS: Although LPTX was not satisfactory as a standard procedure, both SPTX and TPTX are effective treatment methods for PHPT in patients with MEN1. The parathyroidectomy strategy should be based on intraoperative evaluation of the parathyroid glands.
Assuntos
Hiperparatireoidismo Primário/cirurgia , Neoplasia Endócrina Múltipla Tipo 1/cirurgia , Paratireoidectomia/métodos , Adulto , Feminino , Humanos , Hiperparatireoidismo Primário/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
OBJECTIVE: In a phase III trial, Western patients with medullary thyroid cancer (MTC) treated with the oral multikinase inhibitor vandetanib showed significantly improved progression-free survival (PFS) and objective response rate (ORR) compared with placebo. The biology of MTC and pharmacokinetics (PK) are similar for Japanese and Western patients; therefore, similar clinical benefit is anticipated in the Japanese population. This study evaluated the safety and tolerability of vandetanib in Japanese patients with unresectable locally advanced or metastatic MTC. METHODS: This was a phase I/II, open-label, nonrandomized study. Patients received vandetanib (300 mg daily) until objective disease progression. The primary endpoints were safety and tolerability. Secondary endpoints included efficacy and PK. Final data analysis was conducted once all patients with measurable baseline disease had been followed to progression, or for 56 weeks. RESULTS: Fourteen patients received vandetanib. All patients experienced at least one adverse event (AE), and 7 patients (50%) experienced grade ≥3 AEs. Common AEs included diarrhea (79%), hypertension (64%), and rash (43%). Four patients reported a total of five serious AEs (SAEs). Eleven patients (79%) had dose interruptions, and 8 patients (57%) had dose reductions. One patient discontinued treatment because of an SAE (interstitial lung disease). No patients met the prespecified criterion for QTc prolongation. The ORR was 38% and PFS at 12 months was 85%. CONCLUSION: Safety and efficacy data were comparable to those previously reported, and AEs were generally manageable by standard clinical practice or dose modifications. Overall, vandetanib was considered to be beneficial for Japanese MTC patients. ABBREVIATIONS: AE = adverse event CI = confidence interval Css,max = maximum steady-state plasma concentration DCR = disease control rate EGFR = epidermal growth factor receptor ILD = interstitial lung disease MTC = medullary thyroid cancer ORR = objective response rate PFS = progression-free survival PK = pharmacokinetics RECIST = Response Evaluation Criteria in Solid Tumors RET = re-arranged during transfection SAE = serious adverse event VEGFR = vascular endothelial growth factor receptor.
Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Neuroendócrino/tratamento farmacológico , Piperidinas/uso terapêutico , Quinazolinas/uso terapêutico , Neoplasias da Glândula Tireoide/tratamento farmacológico , Adulto , Idoso , Antineoplásicos/efeitos adversos , Antineoplásicos/farmacocinética , Povo Asiático , Carcinoma Neuroendócrino/patologia , Intervalo Livre de Doença , Receptores ErbB/antagonistas & inibidores , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Piperidinas/efeitos adversos , Piperidinas/farmacocinética , Quinazolinas/efeitos adversos , Quinazolinas/farmacocinética , Neoplasias da Glândula Tireoide/patologia , Resultado do TratamentoRESUMO
PURPOSE: To examine the clinical characteristics and survival outcomes of patients with primary hyperparathyroidism (PHPT) in multiple endocrine neoplasia type 1 (MEN1) in relation to the MEN1 gene mutation. METHODS: The study population included the patients, positive for the MEN1 gene mutation, who underwent parathyroidectomy between 1983 and 2009 at a single tertiary referral center. Manifestations of the syndrome, other tumors and causes of death were retrospectively correlated with the specific types and locations of MEN1 gene mutations. RESULTS: Thirty-two patients from 19 families were diagnosed as having MEN1 on genetic examinations. Mutations were most common in exons 2, 7 and 10. A phenotypic analysis of the main MEN1 tumor types among the 32 patients revealed that PHPT was the most common (100 %), followed in order by pancreatic neuroendocrine tumors (PNETs) (53 %) and pituitary tumors (38 %). Death due to MEN1-related disease occurred in five patients (16 %), including malignant PNET in three cases (exons 2, 3), pituitary crisis in one case (exon 2) and thymic cancer in one case (large deletion). CONCLUSIONS: Premature deaths related to MEN1 are due to the development of malignant PNET, pituitary crisis or thymic tumors associated with mutations in exons 2, 3 and a large deletion.