RESUMEN
AIM: The aim of this study was to investigate genetic alterations within breast cancer in the setting of recurrent or de novo stage IV disease. PATIENTS AND METHODS: This study included 22 patients with recurrent breast cancer (n = 19) and inoperable de novo stage IV breast cancer (n = 3). For next generation sequencing, FoundationOneCDx (F1CDx) (Foundation Medicine Inc., Cambridge, MA, USA) was performed in 21 patients and FoundationOneLiquid CDx was performed in 1 patient. RESULTS: Median age was 62.9 years (range, 33.4-82.1). Pathological diagnoses of specimens included invasive ductal carcinoma (n = 19), invasive lobular carcinoma (n = 2), and invasive micropapillary carcinoma (n = 1). F1CDx detected a median of 4.5 variants (range, 1-11). The most commonly altered gene were PIK3CA (n = 9), followed by TP53 (n = 7), MYC (n = 4), PTEN (n = 3), and CDH1 (n = 3). For hormone receptor-positive patients with PIK3CA mutations, hormonal treatment plus a phosphoinositide 3-kinase inhibitor was recommended as the treatment of choice. Patients in the hormone receptor-negative and no human epidermal growth factor receptor 2 expression group had significantly higher tumor mutational burden than patients in the hormone receptor-positive group. A BRCA2 reversion mutation was revealed by F1CDx in a patient with a deleterious germline BRCA2 mutation during poly ADP ribose polymerase inhibitor treatment. CONCLUSION: Guidance on tailored precision therapy with consideration of genomic mutations was possible for some patients with information provided by F1CDx. Clinicians should consider using F1CDx at turning points in the course of the disease.
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Neoplasias de la Mama , Carcinoma , Humanos , Persona de Mediana Edad , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Fosfatidilinositol 3-Quinasas/genética , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/genética , Genómica , Mutación , Secuenciación de Nucleótidos de Alto RendimientoRESUMEN
The objective of this study was to evaluate the intramammary distribution of MRI-detected mass and focus lesions that were difficult to identify with conventional B-mode ultrasound (US) alone. Consecutive patients with lesions detected with MRI but not second-look conventional B-mode US were enrolled between May 2015 and June 2023. Following an additional supine MRI examination, we performed third-look US using real-time virtual sonography (RVS), an MRI/US image fusion technique. We divided the distribution of MRI-detected mammary gland lesions as follows: center of the mammary gland versus other (superficial fascia, deep fascia, and atrophic mammary gland). We were able to detect 27 (84%) of 32 MRI-detected lesions using third-look US with RVS. Of these 27 lesions, 5 (19%) were in the center of the mammary gland and 22 (81%) were located in other areas. We were able to biopsy all 27 lesions; 8 (30%) were malignant and 19 (70%) were benign. Histopathologically, three malignant lesions were invasive ductal carcinoma (IDC; luminal A), one was IDC (luminal B), and four were ductal carcinoma in situ (low-grade). Malignant lesions were found in all areas. During this study period, 132 MRI-detected lesions were identified and 43 (33%) were located in the center of the mammary gland and 87 (64%) were in other areas. Also, we were able to detect 105 of 137 MRI-detected lesions by second-look conventional-B mode US and 38 (36%) were located in the center of the mammary gland and 67 (64%) were in other areas. In this study, 81% of the lesions identified using third-look US with RVS and 64% lesions detected by second-look conventional-B mode US were located outside the center of the mammary gland. We consider that adequate attention should be paid to the whole mammary gland when we perform third-look US using MRI/US fusion technique.
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Neoplasias de la Mama , Imagen por Resonancia Magnética , Ultrasonografía Mamaria , Humanos , Femenino , Imagen por Resonancia Magnética/métodos , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/patología , Persona de Mediana Edad , Adulto , Ultrasonografía Mamaria/métodos , Anciano , Imagen Multimodal/métodos , Mama/diagnóstico por imagen , Carcinoma Ductal de Mama/diagnóstico por imagen , Carcinoma Ductal de Mama/patologíaRESUMEN
BACKGROUND: The purpose of this study was to evaluate the clinical performance of Digital Breast Tomosynthesis guided vacuum-assisted biopsy (DBT-VAB) for microcalcifications in the breast. METHODS: Retrospective review of 131 mammography-guided VABs at our institution were performed. All of the targets were calcification lesion suspicious for cancer. 45 consecutive stereotactic vacuum-assisted biopsies (ST-VABs) and 86 consecutive DBT-VABs were compared. Written informed consent was obtained. Tissue sampling methods and materials were the same with both systems. Student's t-test was used to compare procedure time and the Fisher's exact test was used to compare success rate, complications, and histopathologic findings for the 2 methods. RESULTS: The tissue sampling success rate was 95.6% for ST-VAB (43/45) and 97.7% (84/86) for DBT-VAB. Time for positioning (10.6 ± 6.4 vs. 6.7 ± 5.3 min), time for biopsy (33.4 ± 13.1 vs. 22.5 ± 13.1 min), and overall procedure time (66.6 ± 16.6 min vs. 54.5 ± 13.0 min) were substantially shorter with DBT-VAB (P < 0.0001). There were no differences in the distribution of pathological findings between the 2 groups. CONCLUSION: Depth information and stable visibility of the target provided by DBT images led to quick decisions about target coordinates and improved the clinical performance of microcalcification biopsies.
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Neoplasias de la Mama , Calcinosis , Humanos , Femenino , Japón , Mamografía/métodos , Mama/diagnóstico por imagen , Mama/patología , Biopsia con Aguja , Biopsia Guiada por Imagen/métodos , Biopsia , Calcinosis/diagnóstico por imagen , Calcinosis/patología , Estudios Retrospectivos , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/patologíaRESUMEN
BACKGROUND: There have been no reports of tracheal intubation for airway obstruction after acute thyroid swelling following fine-needle aspiration (FNA) of the thyroid gland. CASE PRESENTATION: A 58-year-old woman with a 22 mm × 13 mm right hypervascular thyroid nodule underwent FNA once with a 22G needle under ultrasonographic guidance. Shortly after the aspiration, ultrasound revealed hypoechoic swelling with a crack-like pattern. The patient was observed under bed rest in the Fowler position and received intravenous steroids. A computed tomography (CT) scan showed swelling not only of the thyroid but also of the retropharyngeal space, and the patient complained of difficulty swallowing saliva. Laryngeal fiberscopy revealed protrusion of the posterior pharyngeal wall, edematous changes in the mucosa of the pharynx and epiglottis, and retention of saliva. The patient was intubated awake and hydrocortisone was administered every 8 h. She was extubated 3 days after FNA and discharged without any complications. CONCLUSIONS: When neck swelling is noticed after FNA, ultrasonographic findings are especially important to assess potential causes. If airway obstruction is suspected, CT findings and fiberscope observation of the pharynx provide particularly useful information.
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Obstrucción de las Vías Aéreas , Nódulo Tiroideo , Obstrucción de las Vías Aéreas/diagnóstico por imagen , Obstrucción de las Vías Aéreas/etiología , Biopsia con Aguja Fina/efectos adversos , Femenino , Humanos , Intubación Intratraqueal/efectos adversos , Persona de Mediana EdadRESUMEN
We recently conducted an open-label phase I/II study to evaluate the efficacy and safety of preoperative and chronic treatment with metyrosine (an inhibitor of catecholamine synthesis) in pheochromocytoma/paraganglioma (PPGL) in Japan. We compared creatinine-corrected metanephrine fractions in spot urine and 24-hour urine samples (the current standard for the screening and diagnosis of PPGLs) from 16 patients to assess the therapeutic effect of metyrosine. Percent changes from baseline in urinary metanephrine (uMN) or normetanephrine (uNMN) were compared between spot and 24-hour urine samples. Mean percent changes in uMN or uNMN in spot and 24-hour urine were -26.36% and -29.27%, respectively. The difference in the percent change from baseline between uMN or uNMN in spot and 24-hour urine was small (-2.90%). The correlation coefficient was 0.87 for percent changes from baseline between uMN or uNMN measured in spot and 24-hour urine. The area under the receiver operator characteristic (ROC) curve of uMN or uNMN measured in spot urine vs. 24-hour urine (reference standard) to assess the efficacy of metyrosine treatment was 0.93. Correlations and ROCs between 24-hour urinary vanillylmandelic acid, adrenaline, and noradrenaline and 24-hour uMN or uNMN were similar to those between spot uMN or uNMN and 24-hour uMN or uNMN. No large difference was observed between spot and 24-hour urine for the assessment of metyrosine treatment by quantifying uMN or uNMN in Japanese patients with PPGLs. These results suggest that spot urine samples may be useful in assessing the therapeutic effect of metyrosine.
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Neoplasias de las Glándulas Suprarrenales/orina , Metanefrina/orina , Paraganglioma/orina , Feocromocitoma/orina , alfa-Metiltirosina/uso terapéutico , Adolescente , Neoplasias de las Glándulas Suprarrenales/tratamiento farmacológico , Neoplasias de las Glándulas Suprarrenales/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Niño , Femenino , Humanos , Japón , Masculino , Persona de Mediana Edad , Normetanefrina/orina , Paraganglioma/tratamiento farmacológico , Paraganglioma/cirugía , Feocromocitoma/tratamiento farmacológico , Feocromocitoma/cirugía , Cuidados Preoperatorios/métodos , Curva ROC , Sensibilidad y Especificidad , alfa-Metiltirosina/administración & dosificación , alfa-Metiltirosina/efectos adversosRESUMEN
Lenvatinib is a molecular-targeting agent that was recently approved in Japan for treatment of curatively unresectable, radioactive iodine-refractory, progressive differentiated thyroid cancer (DTC). Because only a few Japanese patients have received lenvatinib in clinical trials, there are limited domestic data on its safety and efficacy or prognostic factors. Therefore, a prospective observational study has been designed to collect safety and efficacy data in at least 300 patients with curatively unresectable DTC receiving lenvatinib therapy (24 mg/day), in order to find predictors of antitumor activity and survival. Patients with progressive curatively unresectable DTC refractory to radioiodine therapy will be enrolled and the primary endpoint will be overall survival. This study is designed to estimate the 95% confidence intervals of the 1-year and 2-year survival rates with a two-sided width of less than 10%. Secondary endpoints will be the time to treatment failure, time to strategy failure, progression-free survival time with clinical progressive disease, response rate, quality of life, safety, and patient reports. The ultimate goal is to obtain information for developing evidence-based guidelines for treatment of DTC, including recommendations on patient selection, dosages, and duration of treatment. This study has been registered with the UMIN Clinical Trials Registry (UMIN000022243).
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Antineoplásicos/uso terapéutico , Compuestos de Fenilurea/uso terapéutico , Quinolinas/uso terapéutico , Neoplasias de la Tiroides/tratamiento farmacológico , Antineoplásicos/efectos adversos , Estudios de Cohortes , Supervivencia sin Enfermedad , Humanos , Japón , Compuestos de Fenilurea/efectos adversos , Estudios Prospectivos , Calidad de Vida , Quinolinas/efectos adversos , Proyectos de Investigación , Tasa de Supervivencia , Neoplasias de la Tiroides/mortalidadRESUMEN
To assess the efficacy, safety, and pharmacokinetics of metyrosine (an inhibitor of catecholamine synthesis) in patients with pheochromocytoma/paraganglioma (PPGL), we conducted a prospective, multi-center, open-label study at 11 sites in Japan. We recruited PPGL patients aged ≥12 years requiring preoperative or chronic treatment, receiving α-blocker treatment, having baseline urinary metanephrine (uMN) or normetanephrine (uNMN) levels ≥3 times the upper limit of normal values, and having symptoms associated with excess catecholamine. Metyrosine treatment was started at 500 mg/day and modified according to dose-adjustment criteria up to 4,000 mg/day. The main outcome measure was the proportion of patients who achieved at least 50% reduction in uMN or uNMN levels from baseline. Sixteen patients (11 males/5 females) aged 12-86 years participated. After 12 weeks of treatment and at the last evaluation of efficacy, the primary endpoint was achieved in 31.3% of all patients, including 66.7% of those under preoperative treatment and 23.1% of those under chronic treatment. Sedation, anemia, and death were reported in 1 patient each as serious adverse drug reactions during the 24-week treatment. Metyrosine was shown to be tolerated and to relieve symptoms by reducing excess catecholamine in PPGL patients under both preoperative and chronic treatment.
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Neoplasias de las Glándulas Suprarrenales/tratamiento farmacológico , Antineoplásicos/uso terapéutico , Inhibidores Enzimáticos/uso terapéutico , Paraganglioma/tratamiento farmacológico , Feocromocitoma/tratamiento farmacológico , alfa-Metiltirosina/uso terapéutico , Adolescente , Neoplasias de las Glándulas Suprarrenales/patología , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/efectos adversos , Niño , Inhibidores Enzimáticos/efectos adversos , Femenino , Humanos , Japón , Masculino , Persona de Mediana Edad , Paraganglioma/patología , Feocromocitoma/patología , Resultado del Tratamiento , Adulto Joven , alfa-Metiltirosina/efectos adversosRESUMEN
Differentiated thyroid carcinoma (DTC) is generally indolent in nature and, even though it metastasizes to distant organs, the prognosis is normally excellent. In contrast, the overall survival (OS) of patients with radioactive iodine (RAI)-refractory and progressive metastases is dire, because no effective therapies have been available to control the metastatic lesions. However, recently, administration of tyrosine-kinase inhibitors (TKIs) has become a new line of therapy for RAI-refractory and progressive metastases. Previous studies have reported significant improvement regarding the progression-free survival rates of patients with metastatic lesions. However, TKIs cause various severe adverse events (AEs) that damage patients' quality of life and can even be life-threatening. Additionally, metastatic lesions may progress significantly after stopping TKI therapy. Therefore, it is difficult to determine who is a candidate for TKI therapy, as well as how and when physicians start and stop the therapy. The present review, created by Committee of pharmacological therapy for thyroid cancer of the Japanese Society of Thyroid Surgery (JSTS) and the Japan Association of Endocrine Surgeons (JAES) describes how to appropriately use TKIs by describing what we do and do not know about treatment using TKIs.
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Adenocarcinoma/tratamiento farmacológico , Radioisótopos de Yodo/uso terapéutico , Inhibidores de Proteínas Quinasas/uso terapéutico , Neoplasias de la Tiroides/tratamiento farmacológico , Adenocarcinoma/patología , Adenocarcinoma/radioterapia , Quimioterapia Adyuvante , Progresión de la Enfermedad , Humanos , Metástasis de la Neoplasia , Recurrencia Local de Neoplasia , Proteínas Tirosina Quinasas/antagonistas & inhibidores , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/radioterapia , Insuficiencia del TratamientoRESUMEN
The aim of this study was to clarify the histopathological features of anaplastic thyroid carcinoma in patients who achieved long-term survival. We reviewed 88 anaplastic thyroid carcinoma cases in which the patient survived less than 3 months (short-term survival), and 68 anaplastic thyroid carcinoma cases in which the patient survived more than one year (long-term survival) from the database of the Anaplastic Thyroid Carcinoma Research Consortium of Japan. We examined these cases both histologically and immunohistochemically. Six (6.8%) short-term survival cases and 27 (39.7%) long-term survival cases were considered not to be anaplastic thyroid carcinoma after central review. Of these, 12 were revised to papillary carcinoma with squamous cell carcinoma. In cases without chemotherapy, long-term survival was significantly more common if there was a pre-existing tumor, epithelial growth, or lymphocytic infiltration, and short-term survival was more common if neutrophilic infiltration was present. In cases with chemotherapy, long-term survival was significantly more common if epithelial growth or a squamous cell carcinoma component was present, whereas short-term survival was more common in cases with rhabdoid cells. Immunohistochemical results were not related to survival. Some long-term survival cases showed histological findings other than those typically associated with anaplastic thyroid carcinoma. The presence of a pre-existing tumor, epithelial growth, a squamous cell carcinoma component, no neutrophilic infiltration and lymphocytic infiltration may therefore be favorable prognostic factors in anaplastic thyroid carcinoma.
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Carcinoma Anaplásico de Tiroides/mortalidad , Carcinoma Anaplásico de Tiroides/patología , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Japón/epidemiología , Masculino , Persona de Mediana Edad , Pronóstico , Sistema de Registros , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
Measuring the levels of the plasma free metanephrines (PFMs) represents a recently developed and promising test for the diagnosis of pheochromocytoma in the United States and Europe. As this test has not yet been evaluated in Japan, it is necessary to evaluate the diagnostic efficacy of measuring the levels of PFMs compared with the standard measurement of the urinary excretion of metanephrines (uMNs) whose reliability is well established to detect of pheochromocytoma. A total of 101 Japanese subjects clinically suspected of having pheochromocytoma in were included in this study. Subsequently, we prospectively measured the PFMs levels in all patients, compared with those of biochemical markers of the catecholamine secretion and metabolisms in the plasma and urine. All subjects with adrenal tumors underwent tumor excision. Data were available for 84 of the 101 patients, 47 of whom had histopathologically proven pheochromocytoma and 37 were finally diagnosed with non-pheochromocytoma. The results of comparisons in the accuracy of measurement for diagnosis of pheochromocytoma between PFMs and the urinary excretion of metanephrines (uMNs) were 0.980 VS 0.951 for AUC of receiver operatorating characteristic (ROC) curve, 0.957 VS 0.894 for sensitivity, and 0.973 VS 0.946 for specificity, respectively. Although the differences were small, the results of our study definitely demonstrated that measurement of PFMs was not inferior to standard urinary metanephrines (uMNs) measurement, which is established to be the most reliable biochemical method to detect pheochromocytoma. This study clearly shows measuring the PFMs levels to be a reliable and efficient method for diagnosing pheochromocytoma in Japanese patients, as demonstrated in previous reports.
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Neoplasias de las Glándulas Suprarrenales/diagnóstico , Metanefrina/sangre , Normetanefrina/sangre , Feocromocitoma/diagnóstico , Neoplasias de las Glándulas Suprarrenales/sangre , Neoplasias de las Glándulas Suprarrenales/patología , Neoplasias de las Glándulas Suprarrenales/orina , Glándulas Suprarrenales/patología , Adulto , Biomarcadores/sangre , Biomarcadores/química , Biomarcadores/orina , Estudios de Cohortes , Femenino , Hospitales Municipales , Hospitales Universitarios , Humanos , Técnicas para Inmunoenzimas , Japón , Masculino , Metanefrina/química , Metanefrina/orina , Persona de Mediana Edad , Normetanefrina/química , Normetanefrina/orina , Feocromocitoma/sangre , Feocromocitoma/patología , Feocromocitoma/orina , Estudios Prospectivos , Sensibilidad y Especificidad , Solubilidad , Ácido Vanilmandélico/orinaRESUMEN
BACKGROUND AND AIMS: Clinicians sometimes encounter papillary thyroid microcarcinoma (PMC) that is less than 10 mm, associated with lymph node metastasis. In this study, we assessed PMC clinicopathologically to clarify risk factors for poor prognosis. PATIENTS AND METHODS: Fifty-one patients who underwent thyroid surgery at Aichi Medical University from September 2009 to October 2016 were included. Patients were divided into two groups, pEX-positive (23 patients) and pEX-negative (28 patients), based on the pathological finding of thyroid capsule invasion. The former indicates that the tumor infiltrated the thyroid capsule and spread to the neighboring tissue, and the latter indicates no capsule invasion. We analyzed factors such as patient characteristics, pathological findings, and serum levels of thyroid hormones in the two groups. RESULTS: No statistical differences were observed between the two groups in gender distribution or age at surgery. Preoperative cancer diagnoses were established for more patients in the pEX-positive group than in the pEX-negative group (n = 21 and 14, respectively; P = 0.004). The mean (±SD) pathological tumor diameter was 5.42 ± 2.77 in the pEX-negative group and 8.32 ± 1.61 in the pEX-positive group (P < 0.001). No significant differences in preoperative serum levels of free T3, free T4, thyroid-stimulating hormone, or thyroglobulin were observed between the two groups. The odds ratio for node positivity in tumors invading thyroid capsules (pEX-positive) compared to those with no capsule invasion (pEX-negative) was 13.20 (95% confidence interval, 3.45-50.42). Immunohistological staining for phosphatase and tensin homolog deleted from chromosome 10 (PTEN) and Akt (protein kinase B) revealed the facilitation of PTEN and suppression of Akt, which might indicate downregulation of the phosphoinositide 3-kinase-Akt (PI3K-Akt) cascade. DISCUSSION: In general, the prognosis of PMC is favorable. However, the prognosis is less favorable in patients with nodal metastasis or extrathyroidal invasion. It is controversial whether resection is required for proven PMCs. For PMCs associated with extrathyroidal invasion, regional lymph node resection with lobectomy should be performed due to the high risk for lymphatic spread. There might be a possibility that the natural progression of PMC seems to be controlled by the facilitation of PTEN. However, a tumor in the lateral peripheral region of the thyroid parenchyma might be associated with capsule invasion followed by lymphatic spread.
RESUMEN
Background: Although lenvatinib is the preferred treatment for unresectable radioactive iodine-refractory differentiated thyroid cancer (RR-DTC), this agent exerts considerable toxicities, which can lead to frequent dose interruptions and modifications. The adoption of planned drug holidays has been recently suggested as one means of minimizing or avoiding these severe adverse events. Our retrospective study demonstrated that planned drug holidays appear to be a promising strategy for continuing of lenvatinib. However, the benefits of planned drug holidays in a prospective study have yet to be clarified. Here, we investigated the impact of planned drug holidays on clinical outcomes in patients treated with lenvatinib in the COLLECT study. Methods: In COLLECT, a prospective observational study, patients with RR-DTC were treated with lenvatinib in a real-world clinical setting. Lenvatinib was administered orally at a dose of 24 mg daily. Dose modification for toxicities was permitted. Furthermore, planned drug holidays were allowed to avoid severe or intolerable toxicities. The present post hoc analysis focused on evaluating the impact of planned drug holidays on clinical outcomes, including overall survival (OS), time to treatment failure (TTF), time to failure strategy (TFS), and progression-free survival (PFS), in patients in the COLLECT study who were treated with lenvatinib. Results: In total, 262 patients were included. Of the 253 patients evaluable for efficacy, 73 undertook a planned drug holiday at the discretion of the attending physician. OS, TTF, TFS, and PFS were significantly longer in patients who used a planned drug holiday than in those who did not. The planned drug holiday group demonstrated notable clinical outcomes, with a 1-year OS of 95.8% and a 1-year PFS of 94.5%. Moreover, planned drug holidays demonstrated a clinically meaningful advantage in clinical outcomes. The planned drug holiday group had a significantly longer duration of administration at a dose of ≥10 mg. Conclusions: Planned drug holidays for lenvatinib were associated with significantly improved clinical outcomes compared to daily oral administration. Further investigation of the optimal treatment schedule for lenvatinib is warranted. Clinical Trial Registration: UMIN000022243.
Asunto(s)
Antineoplásicos , Compuestos de Fenilurea , Quinolinas , Neoplasias de la Tiroides , Humanos , Quinolinas/uso terapéutico , Quinolinas/efectos adversos , Quinolinas/administración & dosificación , Neoplasias de la Tiroides/tratamiento farmacológico , Neoplasias de la Tiroides/patología , Femenino , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Compuestos de Fenilurea/uso terapéutico , Compuestos de Fenilurea/efectos adversos , Compuestos de Fenilurea/administración & dosificación , Anciano , Adulto , Antineoplásicos/uso terapéutico , Antineoplásicos/efectos adversos , Antineoplásicos/administración & dosificación , Esquema de Medicación , Resultado del Tratamiento , Supervivencia sin ProgresiónRESUMEN
OBJECTIVE: Thymic neuroendocrine tumour (Th-NET) occurs in 2-5% of patients with MEN1 and has high malignant potency accompanying recurrence and distant metastasis. While Th-NET is recognized to develop predominantly in men and heavy smokers, a number of female patients have been reported in the literature. The objective of this study is to clarify the clinical features of MEN1 patients with Th-NET using database analysis. DESIGN/PATIENTS: Clinical data of patients with Th-NET were extracted and analysed from a recently constructed database of Japanese MEN1 patients. RESULTS: Among 560 registered cases, Th-NET was seen in 28 (5·0%) patients. Of note, 36% of patients (10/28) were women; only one patient among those was a smoker and another six patients were non-smokers. Age at diagnosis of Th-NET and MEN1, tumour size, prevalence of other MEN1-related tumours did not differ between male and female patients, and 10-year survival probability was 0·271 ± 0·106. CONCLUSIONS: Although the prevalence of Th-NET in women (3·2%) is significantly lower than that in men (7·6%), a considerable proportion of female patients develop Th-NET. Given that Th-NET is a major determinant of life expectancy of patients, our results alert clinicians who treat patients with MEN1 that surveillance of Th-NET is essential even for female patients without a smoking habit.
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Neoplasia Endocrina Múltiple Tipo 1/patología , Tumores Neuroendocrinos/patología , Neoplasias del Timo/patología , Adulto , Anciano , Femenino , Predisposición Genética a la Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Neoplasia Endocrina Múltiple Tipo 1/sangre , Neoplasia Endocrina Múltiple Tipo 1/diagnóstico , Neoplasia Endocrina Múltiple Tipo 1/genética , Mutación , Tumores Neuroendocrinos/sangre , Tumores Neuroendocrinos/diagnóstico , Tumores Neuroendocrinos/genética , Factores Sexuales , Neoplasias del Timo/sangre , Neoplasias del Timo/diagnóstico , Neoplasias del Timo/genéticaRESUMEN
Protein kinase A (PKA) regulatory subunit type Iα (RIα) is a major regulatory subunit that functions as an inhibitor of PKA kinase activity. We have previously demonstrated that elevated RIα expression is associated with diffuse-to-nodular transformation of hyperplasia in parathyroid glands of renal hyperparathyroidism. The aim of the current study was to determine whether or not RIα expression is increased in adenomas of primary hyperparathyroidism (PHPT), because monoclonal proliferation has been demonstrated in both adenomas and nodular hyperplasia. Surgical specimens comprising 22 adenomas and 11 normal glands, obtained from 22 patients with PHPT, were analyzed. Western blot and immunohistochemical analyses were employed to evaluate RIα expression. PKA activities were determined in several adenomas highly expressing RIα. RIα expression was also separately evaluated in chief and oxyphilic cells using the "Allred score" system. Expression of proliferating cell nuclear antigen (PCNA), a proliferation marker, was also immunohistochemically examined. Western blot analysis revealed that 5 out of 8 adenomas highly expressed RIα, compared with normal glands. PKA activity in adenomas was significantly less than in normal glands. Immunohistochemical analysis further demonstrated high expression of RIα in 20 out of 22 adenomas. In adenomas, the greater RIα expression and more PCNA positive cells were observed in both chief and oxyphilic cells. The present study suggested that high RIα expression could contribute to monoclonal proliferation of parathyroid cells by impairing the cAMP/PKA signaling pathway.
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Adenoma/metabolismo , Subunidad RIalfa de la Proteína Quinasa Dependiente de AMP Cíclico/metabolismo , Hiperparatiroidismo Primario/etiología , Proteínas de Neoplasias/metabolismo , Glándulas Paratiroides/metabolismo , Neoplasias de las Paratiroides/metabolismo , Regulación hacia Arriba , Adenoma/patología , Adenoma/fisiopatología , Adenoma/cirugía , Biomarcadores de Tumor/metabolismo , Western Blotting , Humanos , Inmunohistoquímica , Glándulas Paratiroides/patología , Glándulas Paratiroides/cirugía , Hormona Paratiroidea/sangre , Hormona Paratiroidea/metabolismo , Neoplasias de las Paratiroides/patología , Neoplasias de las Paratiroides/fisiopatología , Neoplasias de las Paratiroides/cirugía , Antígeno Nuclear de Célula en Proliferación/metabolismoRESUMEN
Although postoperative serum thyroglobulin (Tg) is a prognostic indicator for papillary thyroid carcinoma (PTC), it is unreliable when Tg antibody (TgAb) is positive. We evaluated the prognostic significance of changes in serum TgAb levels of pre- and post-total thyroidectomy in TgAb-positive PTC patients. We reviewed our medical charts of 225 TgAb-positive PTC patients in whom TgAb levels were measured before and 1-2 years after total thyroidectomy, performed between April 2002 and March 2007. We divided them into 3 groups based on changes in TgAb levels. Postoperative serum TgAb levels decreased by ≥ 50% in 181 patients (80.4%) (Group 1), by <50% in 22 patients (9.8%) (Group 2), and increased in 22 patients (9.8%) (Group 3). During the follow-up, 3 patients died of the disease and 14 patients had recurrences. All 3 patients who died of PTC were seen only in Groups 2 and 3. Groups 2 and 3 showed similar prognostic outcomes, thus were analyzed together as Group 2+3. Group 1 had significantly better lymph node recurrence-free survival and distant recurrence-free survival than Group 2+3 (96.9% vs. 90.5%, p <0.001, and 98.9% vs. 90.1%, p = 0.004, respectively at 5 years). Multivariate analyses on prognostic factors revealed that classification to Group 2+3 was the strongest indicator for poor prognosis. The present results suggest that changes in TgAb levels following total thyroidectomy can be an important dynamic prognostic factor of PTC patients. Prospective periodical measurements of TgAb are necessary to confirm these findings.
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Autoanticuerpos/sangre , Carcinoma/diagnóstico , Carcinoma/cirugía , Neoplasias de la Tiroides/diagnóstico , Neoplasias de la Tiroides/cirugía , Tiroidectomía , Adolescente , Adulto , Anciano , Carcinoma/sangre , Carcinoma/mortalidad , Carcinoma Papilar , Niño , Femenino , Humanos , Masculino , Persona de Mediana Edad , Periodo Posoperatorio , Valor Predictivo de las Pruebas , Periodo Preoperatorio , Pronóstico , Estudios Retrospectivos , Análisis de Supervivencia , Cáncer Papilar Tiroideo , Neoplasias de la Tiroides/sangre , Neoplasias de la Tiroides/mortalidad , Resultado del Tratamiento , Adulto JovenRESUMEN
PURPOSE: Surgical treatment of local recurrent papillary thyroid carcinoma is still controversial because of the increased morbidity in comparison to primary surgery, and the unclear efficacy. This study analyzed the efficacy and safety of surgery for recurrent disease. METHODS: A retrospective cohort analysis of 86 patients who underwent surgery for local recurrent papillary thyroid carcinoma at a single institution during the period 1979-2009. RESULTS: The cause-specific survival rates of all patients at 5, 10, and 20 years were 86 % (95 % CI 77-95 %), 74 % (95 % CI 62-87 %), and 36 % (95 % CI 18-54 %), respectively. A univariate analysis found that gender, age >45 years at reoperation and macroscopic non-curative surgery for recurrence affected the cause-specific survival rates. The latter two features remained significant in a multivariate analysis. Permanent recurrent nerve paralysis and hypoparathyroidism developed in 4 (4.7 %) and 5 (5.8 %) patients, respectively. CONCLUSIONS: Surgery for local recurrent papillary thyroid carcinoma could be effective when macroscopic curative dissection was possible, and that the procedure was safe and was associated with minimal morbidity. Therefore, repeat surgery for local recurrent papillary thyroid carcinoma is worthwhile.
Asunto(s)
Carcinoma Papilar/cirugía , Recurrencia Local de Neoplasia/cirugía , Neoplasias de la Tiroides/cirugía , Tiroidectomía/métodos , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Carcinoma Papilar/mortalidad , Niño , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/mortalidad , Reoperación , Estudios Retrospectivos , Factores Sexuales , Tasa de Supervivencia , Neoplasias de la Tiroides/mortalidad , Tiroidectomía/mortalidad , Factores de Tiempo , Adulto JovenRESUMEN
BACKGROUND: Invasive lobular carcinoma (ILC) sometimes presents with unique clinical, pathologic, and radiographic features. In this case report, we describe a patient with ILC, whose initial presentation consisted with symptoms secondary to bone-marrow dissemination. In addition, the breast primary was revealed only by magnetic resonance imaging (MRI) followed by real-time virtual sonography (RVS). CASE PRESENTATION: A 51-year-old woman presented to our outpatient clinic with dyspnea on exertion. She had severe anemia (hemoglobin, 5.3 g/dL) and thrombocytopenia (platelet count, 31 × 103/mL). Bone-marrow biopsy was performed to evaluate hematopoietic function. The pathologic diagnosis was bone-marrow carcinomatosis due to metastatic breast cancer. Initial mammography followed by ultrasonography (US) failed to detect the primary tumor. On MRI, a non-mass-enhancement lesion was observed. While second-look US also did not detect the lesion, it was clearly visualized with RVS. We were finally able to biopsy the breast lesion. The pathologic diagnosis was ILC positive for both estrogen receptor and progesterone receptor, with 1 + immunohistochemical staining for human epidermal growth factor receptor 2. This case of ILC was characterized by bone-marrow metastasis. Due to decreased cell adhesion, the risk of bone-marrow metastasis is higher in ILC than in invasive ductal carcinoma, the most prevalent type of breast cancer. Biopsy of the primary lesion, which was initially only detected with MRI, was successfully performed with clear visualization during RVS, which is based on the fusion of MRI and US images. CONCLUSION: In this case report and literature review, we describe the unique clinical characteristics of ILC and a strategy for identifying primary lesions that are initially only visualized with MRI.
RESUMEN
OBJECTIVE: Multiple endocrine neoplasia type 1 (MEN1) is less well recognized in Asian countries, including Japan, than in the West. The clinical features and optimal management of MEN1 have yet to be clarified in Japan. The aim of this study was to clarify the clinical features of Japanese patients with MEN1. DESIGN/PATIENTS: We established a MEN study group designated the 'MEN Consortium of Japan' in 2008, and asked physicians and surgeons to provide clinical and genetic information on patients they had treated. Of 680 registered patients, 560 were analysed. MEASUREMENTS: Clinical and genetic features of Japanese patients with MEN1 were examined. RESULTS: Primary hyperparathyroidism, gastroenteropancreatic neuroendocrine tumours (GEPNET), and pituitary tumours were seen in 94·4%, 58·6% and 49·6% of patients, respectively. The prevalence of insulinoma was higher in the Japanese than in the West (22%vs 10%). In addition, 37% of patients with thymic carcinoids were women, while most were men in western countries. The MEN1 mutation positive rate was 91·7% in familial cases and only 49·3% in sporadic cases. Eight novel mutations were identified. Despite the availability of genetic testing for MEN1, the application of genetic testing, especially presymptomatic diagnosis for at-risk family members appeared to be insufficient. CONCLUSIONS: We established the first extensive database for Asian patients with MEN1. Although the clinical features of Japanese patients were similar to those in western countries, there were several characteristic differences between them.
Asunto(s)
Neoplasia Endocrina Múltiple Tipo 1/diagnóstico , Adolescente , Adulto , Anciano , Niño , Femenino , Pruebas Genéticas , Humanos , Hiperparatiroidismo Primario/diagnóstico , Hiperparatiroidismo Primario/epidemiología , Hiperparatiroidismo Primario/genética , Hiperparatiroidismo Primario/mortalidad , Japón/epidemiología , Masculino , Persona de Mediana Edad , Neoplasia Endocrina Múltiple Tipo 1/epidemiología , Neoplasia Endocrina Múltiple Tipo 1/genética , Neoplasia Endocrina Múltiple Tipo 1/mortalidad , Tumores Neuroendocrinos/diagnóstico , Tumores Neuroendocrinos/epidemiología , Tumores Neuroendocrinos/genética , Tumores Neuroendocrinos/mortalidad , Neoplasias Hipofisarias/diagnóstico , Neoplasias Hipofisarias/epidemiología , Neoplasias Hipofisarias/genética , Neoplasias Hipofisarias/mortalidad , Adulto JovenRESUMEN
The morbidity and mortality of individuals with multiple endocrine neoplasia type 1 (MEN1) can be reduced by early diagnosis of MEN1 and related endocrine tumors. To find factors contributing to early diagnosis, we collected clinical information on MEN1 patients through a MEN study group, "MEN Consortium of Japan" and analyzed the time of initial symptom-dependent detection of parathyroid tumors, gastro-entero-pancreatic neuroendocrine tumors (GEPNETs) and pituitary tumors, and that of tumor detection-dependent MEN1 diagnosis in 560 patients. Main tumors were identified up to 7.0 years after symptoms appeared and there was no difference in age at the diagnosis of GEPNETs alone between probands and family members. In patients with typical symptoms (peptic ulcers, urolithiasis, fasting hypoglycemia, bone fracture/loss and amenorrhea), the mean interval between symptom manifestation and tumor detection was extended up to 9.6 years. In particular, 21.7% (5/23) of patients with amenorrhea were diagnosed with pituitary tumors in under one year. In patients with peptic ulcers (from parathyroid tumors or GEPNETs) and urolithiasis (from parathyroid tumors), the interval was positively correlated with age at tumor detection. The interval between tumor detection and MEN1 diagnosis was also prolonged to approximately four years in patients with fasting hypoglycemia (from GEPNETs) and amenorrhea. A substantial delay in the diagnosis of symptom-related tumors and subsequent MEN1 and inadequate screening of GEPNETs in family members were indicated. A greater understanding of MEN1 may assist medical practitioners to make earlier diagnoses, to share patients' medical information and to give family members sufficient disease information.
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Diagnóstico Tardío , Neoplasia Endocrina Múltiple Tipo 1/diagnóstico , Neoplasia Endocrina Múltiple Tipo 1/fisiopatología , Edad de Inicio , Amenorrea/etiología , Bases de Datos Factuales , Diagnóstico Tardío/prevención & control , Salud de la Familia , Femenino , Humanos , Hipoglucemia/etiología , Japón/epidemiología , Masculino , Neoplasia Endocrina Múltiple Tipo 1/epidemiología , Fracturas Osteoporóticas/etiología , Úlcera Péptica/etiología , Urolitiasis/etiologíaRESUMEN
More than 50% of patients with multiple endocrine neoplasia type 1 (MEN1) develop gastroenteropancreatic neuroendocrine tumors (GEPNETs), and insulinoma is the second most common functioning GEPNET. Compared to other functioning and nonfunctioning GEPNETs in MEN1, insulinoma is considered to develop at a younger age. To clarify the clinical features of insulinoma developed in Japanese patients with MEN1, a recently constructed database of Japanese MEN1 patients was analyzed. Among 560 registered cases, insulinoma was seen in 69 patients and information on age at diagnosis was available for 54 patients. Tumors predominantly occurred in the body and tail of the pancreas. The mean age at diagnosis of insulinoma (34.8 ± 16.7 yrs) was significantly younger than that of gastrinoma (50.6 ± 14.3 yrs) and nonfunctioning tumor (44.7 ± 13.3 yrs) in patients with MEN1. Patients diagnosed as having insulinoma during middle-age (30 - 49 yrs) tended to have a long period from appearance of hypoglycemic symptoms to diagnosis of the tumor. Of note, 13 patients (24%) were diagnosed as having insulinoma before 20 yrs of age. Such young onset was not seen in other GEPNETs. Since the development of GEPNETs during adolescence is quite rare, insulinoma diagnosed before 20 yrs strongly suggests the presence of MEN1 and warrants further investigation, including MEN1 genetic testing. Also, clinicians should be aware that insulinoma can often be missed in middle-aged patients.