RESUMO
OBJECTIVE: This study aimed to investigate expressions and clinical significance of IL-17 and TNF-α after surgery in patients with Hashimoto's disease (HD) combined with thyroid cancer (TC). PATIENTS AND METHODS: From June 2010 to October 2012, 38 patients with HD combined with TC admitted to the oncology department of Tongji Hospital were selected as an experimental group, including three males and 35 females, aged 24-78 years. Forty adults undergoing physical examination during the same period were selected as a control group. All patients in the experimental group were given total endoscopic TC resection. Real-time fluorescence quantification (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) were used to detect the expression levels of serum IL-17 and TNF-α before and 14 days after surgery. Patients with HD combined with TC were divided into high and low expression groups according to the median values of preoperative IL-17 mRNA and TNF-α mRNA. The relationship between IL-17, TNF-α, and prognosis of patients was analyzed through K-M survival curve. RESULTS: The concentrations of IL-17 and TNF-α in serum were also higher than those in control group 14 days after surgery (p < 0.05). qRT-PCT showed that the relative expressions of IL-17 and TNF-α in serum 14 days after surgery were higher than those in control group (p < 0.05). According to the relative expression median of mRNA in IL-17 and TNF-α before surgery, they were divided into high and low expression groups. It was found that the survival rate of high expression groups of IL-17 and TNF-α was lower than that of low expression groups (IL-17, p = 0.028; TNF-α, p = 0.014). CONCLUSIONS: The protein and mRNA of IL-17 and TNF-α in serum of HD patients with TC are higher than those of healthy control group. Expressions of IL-17 and TNF-α can be reduced by surgical resection of focal tissue. IL-17 and TNF-α may be used as potential prognostic indicators of HD patients with TC.
Assuntos
Doença de Hashimoto/sangue , Interleucina-17/sangue , Neoplasias da Glândula Tireoide/sangue , Fator de Necrose Tumoral alfa/sangue , Adenocarcinoma Folicular/sangue , Adenocarcinoma Folicular/cirurgia , Adulto , Carcinoma Medular/sangue , Carcinoma Medular/cirurgia , Estudos de Casos e Controles , Primers do DNA , Ensaio de Imunoadsorção Enzimática , Feminino , Doença de Hashimoto/complicações , Doença de Hashimoto/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/sangue , Prognóstico , RNA Mensageiro/sangue , Estudos Retrospectivos , Câncer Papilífero da Tireoide/sangue , Câncer Papilífero da Tireoide/cirurgia , Neoplasias da Glândula Tireoide/complicações , Neoplasias da Glândula Tireoide/mortalidade , Neoplasias da Glândula Tireoide/cirurgiaRESUMO
Medullary thyroid carcinoma (MTC) is a malignant tumour of the calcitonin-secreting parafollicular C cells of the thyroid gland. Up to 25% of MTC are associated to pathogenic germinal variants on the proto-oncogene RET (locus 10q11.2), which cause Familial Medullary Thyroid Carcinoma (FMTC) or Multiple Endocrine Neoplasia type 2 (MEN2); genetic conditions inherited with autosomal dominant pattern. We present the first report of a Peruvian family with FMTC and a germinal pathogenic variant on RET proto-oncogene, identified with Sanger sequencing. This manuscript also shows a literature review of this hereditary cancer syndrome, where we highlight the relevance of primary prevention and the potential effect on public health in healthy carriers of germinal pathogenic variants.
El cáncer medular de tiroides (CMT) es un tumor maligno de las células C parafoliculares secretoras de calcitonina. Se estima que el 25% de los casos de CMT se asocian a variantes patogénicas a nivel de línea germinal en el protooncogen RET (locus 10q11.2), que son las causantes del desarrollo de Carcinoma Medular de Tiroides Familiar (CMTF) o de la Neoplasia Endocrina Múltiple tipo 2 (NEM2); condiciones genéticas con patrón de herencia autosómico dominante. Presentamos el primer reporte de una familia peruana con CMTF y con variante patogénica identificada a nivel de línea germinal en el gen RET, mediante secuenciamiento Sanger. Este manuscrito también muestra una revisión de la literatura de este síndrome hereditario oncológico, donde se resalta su importancia en la prevención primaria y potencial efecto en la salud pública en casos de portadores de variantes patogénicas germinales aparentemente sanos.
Assuntos
Carcinoma Medular/congênito , Neoplasia Endócrina Múltipla Tipo 2a/genética , Neoplasia Endócrina Múltipla Tipo 2a/patologia , Proteínas Proto-Oncogênicas c-ret/genética , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/patologia , Carcinoma Medular/genética , Carcinoma Medular/patologia , Carcinoma Medular/cirurgia , Feminino , Humanos , Imuno-Histoquímica , Neoplasia Endócrina Múltipla Tipo 2a/cirurgia , Mutação , Proto-Oncogene Mas , Fatores de Risco , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia/métodos , Adulto JovemRESUMO
Introducción: Se estima que del total de los cánceres, el 5-10% tendría una base genética. Actualmente es posible identificar a los individuos con predisposición genética en algunos cánceres como manera de intervenir precozmente en el desarrollo de esta enfermedad. Objetivos: Evaluar la utilidad de la cirugía profiláctica en el cáncer medular de tiroides hereditario. Material y métodos: Este trabajo es una revisión de literatura de diferentes estudios extraídos de bibliotecas electrónicas como Scientific Electronic Library Online (SciELO), MedLine-PubMed y UpToDate, mediante la construcción de preguntas clínicas y términos MeSH enfocados principalmente en la búsqueda específica de información sobre el cáncer medular de tiroides hereditario. Resultados: Los estudios revisados demuestran que la tiroidectomía profiláctica con resección linfática cervical representa el único tratamiento eficaz en el caso del cáncer medular de tiroides hereditario. Conclusiones: La cirugía profiláctica ha demostrado una importante disminución del riesgo de cáncer de tiroides y se considera una conducta de rigor en portadores del gen RET en el cáncer medular de tiroides.
Introduction: Approximately 5-10% of global cancer has a genetic base. Nowadays it is possible to identify those who have a genetic predisposition for some cancers, so they can be treated in short term. Objectives: Evaluate how useful is prophylactic surgery on hereditary Medullary Thyroid Cancer. Materials and methods: This investigation is a literature review of different research papers from electronic databases such as Scientific Electronic Library Online (SciELO), MedLine-PubMed and UpToDate. The research was made with clinical queries and MeSH terms, specially focused on hereditary Medullary Thyroid Cancer. Results: This research shows that prophylactic Thyroidectomy with cervical lymph node resection is the only effective and curative treatment for hereditary Medullary Thyroid Cancer. Conclusions: Prophylactic surgery has proof an important role decreasing the risk on Hereditary Thyroid cancer Syndrome and in RET carriers surgery is considered a must.
Assuntos
Humanos , Carcinoma Medular/congênito , Carcinoma Medular/cirurgia , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia/métodos , Carcinoma Medular/prevenção & controle , Procedimentos Cirúrgicos Profiláticos , Neoplasias da Glândula Tireoide/prevenção & controleRESUMO
PURPOSE OF REVIEW: Medullary thyroid carcinoma (MTC) comprises approximately 4% of all malignant thyroid neoplasms. Although the majority of patients have a good prognosis, a subgroup of patients develops progressive disease and requires systemic therapy. Here, we focused on the current MTC therapeutic approaches and discussed the advantages and disadvantages of molecular targeted therapies. RECENT FINDINGS: Targeted molecular therapies that inhibit RET and other tyrosine kinase receptors involved in angiogenesis have been shown to improve progression-free survival in patients with advanced MTC. Two drugs, vandetanib and cabozantinib, have been approved for the treatment of progressive or symptomatic MTC, and several others have exhibited variable efficacy. No tyrosine kinase inhibitor has been shown to improve survival. Although no definitive recommendation can currently be made, cumulative data indicate that knowledge of the tumor mutational profile may facilitate improvements in targeted therapy for MTC. SUMMARY: Tyrosine kinase inhibitors are effective therapeutic agents for the treatment of progressive MTC. Nevertheless, it is not clear who will benefit the most from therapy, and the decision regarding when and how to initiate the treatment should be made based on the patient's medical history and tumor behavior. Hopefully, in the near future, molecular profiling of MTC can be used to determine the most effective molecular therapeutic target.
Assuntos
Carcinoma Medular/terapia , Neoplasias da Glândula Tireoide/terapia , Carcinoma Medular/diagnóstico , Carcinoma Medular/tratamento farmacológico , Carcinoma Medular/cirurgia , Humanos , Terapia de Alvo Molecular , Inibidores de Proteínas Quinases/uso terapêutico , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/cirurgiaRESUMO
BACKGROUND: Medullary breast cancer is a rare type, considered of good prognosis. OBJECTIVE: To know the epidemiological and clinical characteristics of the population attended in the Hospital Juarez de Mexico, to know if they are alike to described worldwide and if the treatments proposed internationally are applicable for this hospitable center. METHODS: We performed a retrospective analysis. Reviewing the records with histopathologic diagnosis of medullary breast cancer from February 1993 to February 2011. Finding 41 patients in the oncology unit of the institution. RESULTS: We report an incidence of 3.04%, originating in 11 Mexican States, with a low to middle socioeconomic level in 39.02%. The average age at the time of diagnosis was 50 years. No family history was reported but some patients had medical history for type 2 diabetes, hypertension and previous breast cancer. 63.41% were menopausal. The average clinical size of the tumor was 58 mm. The 63% of the cases were located in the left breast. The 53.1% were clinical stages I and II, 46.3% were clinical stages III and in 9.6% of the cases primary tumor could not be assessed. Only 47% of the patients had positive axillary lynph nodes at diagnosis. The inmunohistochemestry was only reported in 14 of the 41 patients, according to the molecular classification of breast cancer: 8 were triple negative, 2 luminal A, 1 luminal B and 3 Her2neu. CONCLUSIONS: The Mexican population presents epidemiological and clinical characteristics similar to those patients described in other studies worldwide.
Antecedentes: el carcinoma de mama, variante medular, es poco frecuente y de buen pronóstico. Objetivo: conocer las características epidemiológicas y clínicas de la población atendida en el Hosital Juárez de México, saber si se asemejan a las descritas a nivel mundial y si los tratamientos propuestos internacionalmente son aplicables para este centro hospitalario. Material y métodos: estudio retrospectivo y descriptivo de 41 expedientes de pacientes con cáncer de mama tipo medular atendidas entre febrero de 1993 y febrero 2011. Resultados: se encontró que la incidencia de cáncer de mama de tipo medular fue de 3.04% en pacientes originarias de 11 estados mexicanos, con edad promedio de 50 años, nivel socioeconómico medio bajo para 39.02%, sin antecedentes familiares pero sí personales patológicos para: diabetes mellitus tipo 2, hipertensión arterial sistémica y cáncer de mama previo. Eran postmenopáusicas 63.41%. El promedio del tamaño clínico del tumor fue 58 mm, localizado en 63% de los casos en la mama izquierda. Los estadios clínicos fueron: 53.1% en I y II, 46.3% en III y 9.6% no etapificable. El 47% de las pacientes tenía ganglios linfáticos axilares positivos al momento del diagnóstico. La inmunohistoquímica sólo se reportó en 14 de las 41 pacientes; de acuerdo con la clasificación molecular para cáncer de mama: 8 fueron triple negativo, 2 luminal A, 1 luminal B y 3 Her2Neu. Conclusión: la población mexicana tiene características epidemiológicas y clínicas similares a las de las pacientes descritas en estudios internacionales.
Assuntos
Neoplasias da Mama/epidemiologia , Carcinoma Medular/epidemiologia , Idoso , Biomarcadores Tumorais , Neoplasias da Mama/química , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Carcinoma Medular/química , Carcinoma Medular/diagnóstico , Carcinoma Medular/patologia , Carcinoma Medular/cirurgia , Comorbidade , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Humanos , Hipertensão/epidemiologia , Incidência , Menopausa , México/epidemiologia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Segunda Neoplasia Primária/epidemiologia , Segunda Neoplasia Primária/patologia , Prognóstico , Estudos Retrospectivos , Fatores Socioeconômicos , Taxa de Sobrevida , Neoplasias de Mama Triplo Negativas/química , Neoplasias de Mama Triplo Negativas/epidemiologia , Neoplasias de Mama Triplo Negativas/patologiaRESUMO
Background: Medullary thyroid cancer (MTC) represents approximately 5% of all thyroid cancers. Surgery is the only curative treatment, which includes total thyroidectomy and in most cases, neck dissection. Aim: To report our 10-year experience with surgical treatment of MTC. Material and Methods: Review of medical records and pathology reports of a university hospital. We retrieved data from 28 patients aged 47.2 ± 16 years (21 women) operated for a MTC treated between June 2002 and June 2012. Results: In 20 patients, MTC was diagnosed in the preoperative period. Total thyroidectomy was performed in all cases and included a neck dissection in 24 patients. Median follow-up was 48 (2-120) months. Twenty-five patients (89.2%) achieved complete remission of the disease and three had disease recurrence. There were no deaths during the follow up. Conclusions: The diagnosis of MTC is mainly based on cytology. Total thyroidectomy with neck dissection is the treatment of choice. An early-stage diagnosis is associated with low rates of recurrence and absence of mortality.
Assuntos
Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Medular/cirurgia , Neoplasias da Glândula Tireoide/cirurgia , Calcitonina/sangue , Carcinoma Medular/diagnóstico , Diagnóstico Precoce , Seguimentos , Esvaziamento Cervical , Cuidados Pré-Operatórios , Prognóstico , Indução de Remissão , Neoplasias da Glândula Tireoide/diagnóstico , TireoidectomiaRESUMO
BACKGROUND: Medullary thyroid cancer (MTC) represents approximately 5% of all thyroid cancers. Surgery is the only curative treatment, which includes total thyroidectomy and in most cases, neck dissection. AIM: To report our 10-year experience with surgical treatment of MTC. MATERIAL AND METHODS: Review of medical records and pathology reports of a university hospital. We retrieved data from 28 patients aged 47.2 ± 16 years (21 women) operated for a MTC treated between June 2002 and June 2012. RESULTS: In 20 patients, MTC was diagnosed in the preoperative period. Total thyroidectomy was performed in all cases and included a neck dissection in 24 patients. Median follow-up was 48 (2-120) months. Twenty-five patients (89.2%) achieved complete remission of the disease and three had disease recurrence. There were no deaths during the follow up. CONCLUSIONS: The diagnosis of MTC is mainly based on cytology. Total thyroidectomy with neck dissection is the treatment of choice. An early-stage diagnosis is associated with low rates of recurrence and absence of mortality.
Assuntos
Carcinoma Medular/cirurgia , Neoplasias da Glândula Tireoide/cirurgia , Adulto , Calcitonina/sangue , Carcinoma Medular/diagnóstico , Carcinoma Neuroendócrino , Diagnóstico Precoce , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Esvaziamento Cervical , Cuidados Pré-Operatórios , Prognóstico , Indução de Remissão , Neoplasias da Glândula Tireoide/diagnóstico , TireoidectomiaAssuntos
Humanos , Feminino , Pessoa de Meia-Idade , Carcinoma Medular/cirurgia , Carcinoma Medular , Calcitonina , TireoidectomiaRESUMO
We briefly review the surgical approaches to medullary thyroid carcinoma associated with multiple endocrine neoplasia type 2 (medullary thyroid carcinoma/multiple endocrine neoplasia type 2). The recommended surgical approaches are usually based on the age of the affected carrier/patient, tumor staging and the specific rearranged during transfection codon mutation. We have focused mainly on young children with no apparent disease who are carrying a germline rearranged during transfection mutation. Successful management of medullary thyroid carcinoma in these cases depends on early diagnosis and treatment. Total thyroidectomy should be performed before 6 months of age in infants carrying the rearranged during transfection 918 codon mutation, by the age of 3 years in rearranged during transfection 634 mutation carriers, at 5 years of age in carriers with level 3 risk rearranged during transfection mutations, and by the age of 10 years in level 4 risk rearranged during transfection mutations. Patients with thyroid tumor >5 mm detected by ultrasound, and basal calcitonin levels >40 pg/ml, frequently have cervical and upper mediastinal lymph node metastasis. In the latter patients, total thyroidectomy should be complemented by extensive lymph node dissection. Also, we briefly review our data from a large familial medullary thyroid carcinoma genealogy harboring a germline rearranged during transfection Cys620Arg mutation. All 14 screened carriers of the rearranged during transfection Cys620Arg mutation who underwent total thyroidectomy before the age of 12 years presented persistently undetectable serum levels of calcitonin (<2 pg/ml) during the follow-up period of 2-6 years. Although it is recommended that preventive total thyroidectomy in rearranged during transfection codon 620 mutation carriers is performed before the age of 5 years, in this particular family the surgical intervention performed before the age of 12 years led to an apparent biochemical cure.
Assuntos
Carcinoma Medular/cirurgia , Excisão de Linfonodo , Neoplasia Endócrina Múltipla Tipo 2a/cirurgia , Neoplasias da Glândula Tireoide/cirurgia , Calcitonina/sangue , Carcinoma Medular/genética , Carcinoma Neuroendócrino , Criança , Mutação em Linhagem Germinativa/genética , Humanos , Neoplasia Endócrina Múltipla Tipo 2a/genética , Pescoço , Proteínas Proto-Oncogênicas c-ret/genética , Neoplasias da Glândula Tireoide/genéticaRESUMO
OBJECTIVE: Since the first data from a patient with colorectal adenocarcinoma are obtained by biopsy, this study evaluated the accuracy of diagnosis by biopsy as compared with the diagnostic potential of the surgical specimen, considering the histological type, grade of differentiation, and immunohistochemical expression of p53. METHODS: The specimens were obtained from 80 patients assisted at Hospital São Paulo. The biopsy and surgical specimen sections were stained by hematoxylin-eosin and immunohistochemistry and compared by 3 pathologists blinded to the evaluations. RESULTS: The accuracy for the histological types was 88%. The grade of differentiation presented an accuracy of 70% with Kappa = .48. The expression of protein p53 exhibited an accuracy of 68% with Kappa = .22. CONCLUSION: The preoperative biopsy of colorectal adenocarcinoma presented good accuracy compared with histopathological examination of the surgical specimen, but with weak to moderate effective degree of agreement between the results.