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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
BACKGROUND: This cross-sectional study compared patient-reported outcomes of low-risk papillary thyroid carcinoma (PTC, T1N0M0) between patients who underwent active surveillance (AS) and those who received immediate surgery, METHODS: Using the State-Trait Anxiety Inventory, Short-Form 36 version 2, and a visual analog scale for neck symptoms, 249 patients under AS and 32 patients underwent immediate surgery were compared. To match the difference in time from the onset of treatment to the survey, we conducted propensity score matching. We also investigated factors affecting anxiety in patients under AS in multiple linear regression analysis. RESULTS: In the entire group, patients under AS had significantly longer time from the onset to the survey than patients underwent immediate surgery (7.9 vs. 4.0 years). After matching, AS group showed significantly better trait anxiety and mental component summary (MCS) compared to surgery group, while surgery group showed better role-social component summary. AS group also had significantly better MCS than the Japanese norm-based score. Surgery group displayed worse neck symptoms than AS group. Among AS group, trait anxiety and time from the onset were significant predictors of state anxiety. Compared with the group with < 5 years since starting AS, the group with ≥ 5 years of follow-up showed a significantly better state anxiety only in patients with better trait anxiety. CONCLUSIONS: Low-risk PTC patients under AS showed better trait anxiety and mental health than surgery group. After a certain period, the anxiety of patients under AS seems to be improved, especially in patients with better trait anxiety.
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Neoplasias da Glândula Tireoide , Humanos , Câncer Papilífero da Tireoide/cirurgia , Câncer Papilífero da Tireoide/patologia , Neoplasias da Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/patologia , Estudos Transversais , Conduta Expectante , Risco , TireoidectomiaRESUMO
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
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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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
The incidence of thyroid carcinoma has been increasing worldwide. This is interpreted as an increase in the incidental detection of papillary thyroid microcarcinomas (PTMCs). However, mortality has not changed, suggesting overdiagnosis and overtreatment. Prospective clinical trials of active surveillance for low-risk PTMC (T1aN0M0) have been conducted in two Japanese institutions since the 1990s. Based on the favorable outcomes of these trials, active surveillance has been gradually adopted worldwide. A task force on the management of PTMC in adults organized by the Japan Thyroid Association therefore conducted a systematic review and has produced the present position paper based on the scientific evidence concerning active surveillance. This paper indicates evidence for the increased incidence of PTMC, favorable surgical outcomes for low-risk PTMC, recommended criteria for diagnosis using fine needle aspiration cytology, and evaluation of lymph node metastasis (LNM), extrathyroidal extension (ETE) and distant metastasis. Active surveillance has also been reported with a low incidence of disease progression and no subsequent recurrence or adverse events on survival if conversion surgery was performed at a slightly advanced stage. Active surveillance is a safe and valid strategy for PTMC, because it might preserve physical quality of life and reduce 10-year medical costs. However, some points should be noted when performing active surveillance. Immediate surgery is needed for PTMC showing high-risk features, such as clinical LNM, ETE or distant metastasis. Active surveillance should be performed under an appropriate medical team and should be continued for life.
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Câncer Papilífero da Tireoide/terapia , Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/terapia , Adulto , Humanos , Japão , Câncer Papilífero da Tireoide/patologia , Câncer Papilífero da Tireoide/cirurgia , Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/cirurgia , Conduta ExpectanteRESUMO
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
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.
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Hiperparatireoidismo Primário/cirurgia , Neoplasia Endócrina Múltipla Tipo 1/cirurgia , Paratireoidectomia/métodos , Adulto , Feminino , Humanos , Hiperparatireoidismo Primário/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
BACKGROUND: Chronic inflammation induces DNA damage and promotes cell proliferation, thereby increasing the risk of cancer. DNA polymerase κ (Pol κ), involved in translesion DNA synthesis, counteracts mutagenesis induced by inflammation in the colon of mice. In the present study, we examined whether Pol κ suppressed inflammation-induced colon tumorigenesis by treating inactivated Polk knock-in (Polk-/-) mice with dextran sulfate sodium (DSS), an inducer of colon inflammation. RESULTS: Male and female Polk-/- and Polk+/+ mice were administered 2% DSS in drinking water for six consecutive days, succeeded via a recovery period of 16 days, followed by 2% DSS for another two days. DSS treatment strongly induced colitis, and the severity of colitis was higher in Polk-/- mice than in Polk+/+ mice. The mice were sacrificed after 19 weeks from the initiation of the first DSS treatment and subjected to pathological examination and mutation analysis. DSS treatment induced colonic dysplasia, and the multiplicity of dysplasia was higher in Polk-/- mice than in Polk+/+mice. Some of the dysplasias in Polk-/- mice exhibited ß-catenin-stained nucleus and/or cytoplasm. Mutation frequencies in the gpt reporter gene were increased by DSS treatment in Polk-/- mice, and were higher than those in Polk+/+ mice. CONCLUSIONS: Pol κ suppresses inflammation and inflammation-induced dysplasia as well as inflammation-induced mutagenesis. The possible mechanisms by which Pol κ suppresses colitis- and colitis-induced dysplasia are discussed.
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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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Primary aldosteronism is often associated with heart failure (HF), and is reportedly difficult to treat in some cases. We report a case of severe HF associated with primary aldosteronism. A patient with HF, who was suspected of having primary aldosteronism, was referred to and examined at our hospital. After detailed examination, the patient was diagnosed with exacerbation of HF, and was treated at our department. Catheterization after admission revealed Forrester class IV HF. The patient was treated with catecholamine infusion in combination with medical treatment including mineralocorticoid receptor antagonists. The patient was diagnosed with hypertension due to primary aldosteronism and intractable secondary HF with increased peripheral vascular resistance. An open adrenalectomy was successfully performed under intra-aortic balloon pumping. Right heart catheterization, performed soon thereafter, demonstrated improvement in the patient's blood pressure and hemodynamics. We speculate that the improved cardiac function resulted from a reduction in the vascular resistance, as a consequence of the adrenalectomy.
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CONTEXT: Pheochromocytoma and paraganglioma (PPGL) may appear as a complication of cyanotic congenital heart disease (CCHD-PPGL) with frequent EPAS1 mutations, suggesting a close link between EPAS1 mutations and tissue hypoxia in CCHD-PPGL pathogenesis. OBJECTIVE: Our aim is to further investigate the role of EPAS1 mutations in the hypoxia-driven mechanism of CCHD-PPGL pathogenesis, particularly focusing on metachronous and/or multifocal CCHD-PPGL tumors. METHODS: We performed whole-exome sequencing (WES) for somatic and germline mutations in 15 PPGL samples from 7 CCHD patients, including 3 patients with metachronous and/or multifocal tumors, together with an adrenal medullary hyperplasia (AMH) sample. RESULTS: We detected EPAS1 mutations in 15 out of 16 PPGL/AMH samples from 7 cases. Conspicuously, all EPAS1 mutations in each of 3 cases with multifocal or metachronous tumors were mutually independent and typical examples of parallel evolution, which is suggestive of strong positive selection of EPAS1-mutated clones. Compared to 165 The Cancer Genome Atlas non-CCHD-PPGL samples, CCHD-PPGL/AMH samples were enriched for 11p deletions (13/16) and 2p amplifications (4/16). Of particular note, the multiple metachronous PPGL tumors with additional copy number abnormalities developed 18 to 23 years after the resolution of hypoxemia, suggesting that CCHD-induced hypoxic environments are critical for positive selection of EPAS1 mutants in early life, but may no longer be required for development of PPGL in later life. CONCLUSION: Our results highlight a key role of activated hypoxia-inducible factor 2α due to mutated EPAS1 in positive selection under hypoxic environments, although hypoxemia itself may not necessarily be required for the EPAS1-mutated clones to progress to PPGL.
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Neoplasias das Glândulas Suprarrenais , Cardiopatias Congênitas , Paraganglioma , Feocromocitoma , Neoplasias das Glândulas Suprarrenais/complicações , Neoplasias das Glândulas Suprarrenais/genética , Neoplasias das Glândulas Suprarrenais/patologia , Cardiopatias Congênitas/complicações , Cardiopatias Congênitas/genética , Humanos , Hipóxia/genética , Paraganglioma/complicações , Paraganglioma/genética , Paraganglioma/patologia , Feocromocitoma/complicações , Feocromocitoma/genética , Feocromocitoma/patologiaRESUMO
BACKGROUND: Metastasis to the breast is rare. We herein report a patient with metastatic medullary thyroid carcinoma to the breast for whom measuring the calcitonin level was an important clue to the correct diagnosis. CASE PRESENTATION: A 54-year-old woman visited our hospital for the treatment of recurrent metastatic medullary thyroid carcinoma due to multiple endocrine neoplasia 2A and breast cancer. Positron emission tomography performed before the operation for metastatic medullary thyroid carcinoma recurrence in the neck showed the accumulation of 18F-fluorodeoxyglucose in the bilateral breast at sites other than the disease in the neck. Ultrasonography revealed multiple tumors in both breasts. A core needle biopsy of three breast tumors was performed. Microscopically, the tumor cells showed solid growth and did not show a tubular structure. She was diagnosed with triple-negative invasive ductal carcinoma. Post-operative positron emission tomography was performed as the serum calcitonin level increased after the operation. The accumulation of 18F-fluorodeoxyglucose in the bilateral breast tumors and lymph nodes in the neck was noted. The possibility of the breast tumors being metastasis of metastatic medullary thyroid carcinoma was considered. Needle aspiration was performed for three breast tumors. The calcitonin level of the washout fluid was measured and found to be ≥ 17,500 pg/mL. Immunohistochemistry showed that the tumor cells were calcitonin-positive and gross cystic disease fluid protein-15-negative. Vandetanib was started as recurrent metastatic medullary thyroid carcinoma with breast metastasis was finally diagnosed. The serum calcitonin level decreased after 1 month. CONCLUSION: Although breast metastasis of medullary thyroid carcinoma is rare, a correct diagnosis is indispensable for appropriate treatment. When a breast tumor shows atypical morphological features for breast cancer according to the histopathology in a patient with a history of cancer, metastasis to the breast should be considered. Calcitonin measurement of the needle washout fluid was useful for confirming metastatic medullary thyroid carcinoma.
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Background: The question of how to manage patients with low-risk papillary thyroid microcarcinoma (PTMC; T1aN0M0) has recently become an important clinical issue. Two Japanese centers have conducted prospective clinical trials of active surveillance (AS) for low-risk PTMC since the 1990s, reporting favorable outcomes. This policy has thus seen gradual adoption worldwide to avoid overtreatment. Not all PTMCs are suitable for AS, however, and many physicians still hesitate to apply the management policy in daily clinical practice. A task force on management for PTMC created by the Japan Association of Endocrine Surgery collected and analyzed bibliographic evidence and has produced the present consensus statements regarding indications and concrete strategies for AS to facilitate the management of adult patients diagnosed with low-risk PTMC. Summary: These statements provide indications for AS in adult patients with T1aN0M0 low-risk PTMC. PTMCs with clinical lymph node metastasis, distant metastasis, recurrent laryngeal nerve (RLN) paralysis due to carcinoma invasion, or protrusion into the tracheal lumen warrant immediate surgery. Tumors suspected of aggressive subtypes on cytology are recommended for immediate surgery. Immediate surgery is also recommended for tumors adherent to the trachea or located along the course of the RLN. Practical strategies include diagnosis, decision-making, follow-up, and monitoring related to the implementation of AS. The rate of low-risk PTMC progression is lower in older patients. However, we recommend continuing AS as long as circumstances permit. Future tasks in optimizing management for low-risk PTMC are also described, including molecular markers and patient-reported outcomes. Conclusions: An appropriate multidisciplinary team is necessary to accurately evaluate primary tumors and lymph nodes at the beginning of and during AS, and to adequately reach a shared-decision with individual patients. If appropriately applied, AS of low-risk PTMC is a safe management strategy offering favorable outcomes and preserves quality of life at low cost.
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Carcinoma Papilar/terapia , Neoplasias da Glândula Tireoide/terapia , Conduta Expectante/normas , Carcinoma Papilar/secundário , Tomada de Decisão Clínica , Consenso , Humanos , Japão , Estadiamento de Neoplasias , Medição de Risco , Fatores de Risco , Neoplasias da Glândula Tireoide/patologia , Fatores de Tempo , Resultado do TratamentoRESUMO
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
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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Hyperpolarized-activated cyclic nucleotide-gated (HCN) channels underlie hyperpolarization-activated current (Ih) and are involved in controlling the excitability and electrical responsiveness of neurons. Absence epilepsy is clinically defined by a sudden, brief impairment of consciousness and behavioral arrest. Spike-and-wave discharges (SWDs) on electroencephalograms (EEG) are a diagnostic hallmark of absence epilepsy. In rat models of absence epilepsy, impaired function or expression of HCN1, a subtype of HCN channels, has been found. Here, to evaluate whether HCN1 deficiency causes absence epilepsy in rats, we developed Hcn1-knockout rats by transcription activator-like effector nuclease mutagenesis. The cortical and hippocampal pyramidal neurons of these rats displayed a significant reduction of Ih, a pronounced hyperpolarizing shift of the resting membrane potential, and increased input resistance, which indicated that the Hcn1-knockout rats were deficient in HCN1 function. The Hcn1-knockout rats were also more vulnerable to pentylenetetrazol-induced acute convulsions. More importantly, they exhibited spontaneous SWDs, which were accompanied by behavioral arrest, both of which were suppressed by ethosuximide. These results confirm the involvement of the HCN1 subunit in the regulation of input resistance and provide direct evidence that a deficiency of HCN1 caused absence epilepsy in rats.
Assuntos
Epilepsia Tipo Ausência/metabolismo , Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização/metabolismo , Canais de Potássio/metabolismo , Potenciais de Ação/fisiologia , Animais , Córtex Cerebral/metabolismo , Canais de Cátion Regulados por Nucleotídeos Cíclicos/metabolismo , Modelos Animais de Doenças , Eletroencefalografia , Epilepsia Tipo Ausência/etiologia , Técnicas de Inativação de Genes , Hipocampo/metabolismo , Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização/genética , Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização/fisiologia , Masculino , Potenciais da Membrana/fisiologia , Neurônios/metabolismo , Técnicas de Patch-Clamp , Canais de Potássio/genética , Canais de Potássio/fisiologia , Células Piramidais/fisiologia , Ratos , Ratos Endogâmicos F344 , Convulsões/metabolismoRESUMO
Essential tremor (ET) is a common movement disorder with a poorly understood etiology. The TRM/Kyo mutant rat, showing spontaneous tremor, is an animal model of ET. Recently, we demonstrated that tremors in these rats emerge when two mutant loci, a missense mutation in the hyperpolarization-activated cyclic nucleotide-gated potassium channel 1 (Hcn1) and the tremor (tm) deletion, are present simultaneously. However, we did not identify which gene within the tm deletion causes tremor expression in TRM/Kyo rats. A strong candidate among the 13 genes within the tm deletion is aspartoacylase (Aspa), because some Aspa-knockout mouse strains show tremor. Here, we generated Aspa-knockout rats using transcription activator-like effector nuclease technology and produced Aspa/Hcn1 double-mutant rats by crossing Aspa-knockout rats with Hcn1-mutant rats. The Aspa-knockout rats carried nonsense mutations in exon 4; and ASPA proteins were not detectable in their brain extracts. They showed elevated levels of N-acetyl-L-aspartate (NAA) in urine and spongy vacuolation and abnormal myelination in the central nervous system, but no tremor. By contrast, Aspa/Hcn1 double-mutant rats spontaneously showed tremors resembling those in TRM/Kyo rats, and the tremor was suppressed by drugs therapeutic for ET but not for parkinsonian tremor. These findings indicated that the lack of the Aspa gene caused tremor expression in TRM/Kyo rats. Our animal model suggested that the interaction of NAA accumulation due to ASPA deficiency with an unstable neuronal membrane potential caused by HCN1 deficiency was involved in tremor development.
Assuntos
Amidoidrolases/genética , Códon sem Sentido , Tremor Essencial/genética , Deleção de Genes , Estudos de Associação Genética , Mutação de Sentido Incorreto , Amidoidrolases/deficiência , Animais , Ácido Aspártico/análogos & derivados , Ácido Aspártico/urina , Sistema Nervoso Central/patologia , Modelos Animais de Doenças , Epistasia Genética , Tremor Essencial/patologia , Éxons/genética , Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização/deficiência , Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização/genética , Camundongos , Canais de Potássio/deficiência , Canais de Potássio/genética , Ratos , Ratos MutantesRESUMO
PURPOSE: To report the 2-year results of reduced-fluence photodynamic therapy (RF-PDT) combined with intravitreal ranibizumab (IVR) for typical age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV). METHODS: Twenty-four previously untreated eyes of 23 AMD patients with decimal best-corrected visual acuity (BCVA) of less than 0.7 received the combined therapy, followed by retreatments as needed over the subsequent 2 years. When the BCVA was better than or equal to 0.7, only 3 monthly IVR injections were performed during the retreatment. RESULTS: The BCVAs were maintained in 7 of 10 typical AMD eyes and in 13 of 14 PCV eyes at month 24. The mean BCVA improved in the PCV group (P < 0.05) but not in the typical AMD group. The central foveal thickness decreased in both groups (P < 0.01, P < 0.001). The mean numbers of the total PDT and IVR injections were 1.8 and 7.2 in the typical AMD group and 1.8 and 6.4 in the PCV group. CONCLUSION: After RF-PDT combined therapy with administration of retreatments as needed that consisted of either 3 IVR injections alone or combined therapy, the BCVA was maintained in typical AMD and improved in PCV during a 2-year follow-up period.
Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Doenças da Coroide/tratamento farmacológico , Corioide/irrigação sanguínea , Degeneração Macular/tratamento farmacológico , Fotoquimioterapia/métodos , Idoso , Idoso de 80 Anos ou mais , Doenças da Coroide/complicações , Doenças da Coroide/diagnóstico , Feminino , Angiofluoresceinografia , Seguimentos , Fundo de Olho , Humanos , Injeções Intravítreas , Degeneração Macular/complicações , Degeneração Macular/diagnóstico , Masculino , Pessoa de Meia-Idade , Ranibizumab , Estudos Retrospectivos , Tomografia de Coerência Óptica , Resultado do Tratamento , Acuidade VisualRESUMO
BIG2 is a guanine nucleotide exchange factor (GEF) for the ADP-ribosylation factor (ARF) family of small GTPases, which regulate membrane association of COPI and adaptor protein (AP)-1 coat protein complexes. A fungal metabolite, brefeldin A (BFA), inhibits ARF-GEFs and leads to redistribution of coat proteins from membranes to the cytoplasm and membrane tubulation of the Golgi complex and the trans-Golgi network (TGN). To investigate the function of BIG2, we examined the effects of BIG2-overexpression on the BFA-induced redistribution of ARF, coat proteins, and organelle markers. The BIG2 overexpression blocked BFA-induced redistribution from membranes of ARF1 and the AP-1 complex but not that of the COPI complex. These observations indicate that BIG2 is implicated in membrane association of AP-1, but not that of COPI, through activating ARF. Furthermore, not only BIG2 but also ARF1 and AP-1 were found as queues of spherical swellings along the BFA-induced membrane tubules emanating from the TGN. These observations indicate that BFA-induced AP-1 dissociation from TGN membranes and tubulation of TGN membranes are not coupled events and suggest that a BFA target other than ARF-GEFs exists in the cell.