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AIM: Papillary thyroid microcarcinoma (PTMC) is increasing in incidence. Despite its excellent clinical outcomes, there is still debate regarding which surgical approach is more appropriate for PTMC, procedures including hemithyroidectomy (HT), total thyroidectomy (TT), and completion thyroidectomy (CT) after initial HT and histopathologic examination confirming a PTMC. Here we report our experience in the surgical management of PTMC. METHODS: We conducted a retrospective evaluation of all patients who received a postoperative diagnosis of PTMC between January 2001 and January 2016. Every patient was divided according to the type of surgery performed (TT or HT alone). Follow-up consisted of regular clinical and neck ultrasonographic examination. Clinical and histopathological parameters (e.g. age, sex, lesion size, histological features, multifocality, lymph node metastases, BRAF status when available) as well as clinical outcomes (e.g. complications rates, recurrence, overall survival) were analyzed. RESULTS: Group A consisted of 86 patients who underwent TT, whereas Group encompassed 19 patients who underwent HT. Mean follow-up period was 58.5 months. In Group A, one patient (1.2%) experienced recurrence in cervical lymph nodes with need for reoperation. In Group B, eight patients (42%) underwent completion thyroidectomy after histopathological examination confirming PTMC, while one patient (5.3%) developed PTMC in the contralateral lobe with need for reoperation at 2 years after initial surgery. Multifocality was found in 19 patients in Group A (22%). Of these, 14 presented bilobar involvement, whereas in 3 cases multifocality involved only one lobe. 1 patient in Group B (5.3%) presented with unilateral multifocal PTMC (p = 0.11). CONCLUSIONS: Low-risk patients with PTMC may benefit from a more conservative treatment, e.g. HT followed by close follow-up. However, appropriate selection of patients based on risk stratification is the key to differentiate therapy options and gain better results.
Assuntos
Carcinoma Papilar/cirurgia , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia/métodos , Adulto , Carcinoma Papilar/patologia , Feminino , Seguimentos , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/patologia , Resultado do TratamentoRESUMO
The LKB1 tumor suppressor gene encodes a master kinase that coordinates the regulation of energetic metabolism and cell polarity. We now report the identification of a novel isoform of LKB1 (named ΔN-LKB1) that is generated through alternative transcription and internal initiation of translation of the LKB1 mRNA. The ΔN-LKB1 protein lacks the N-terminal region and a portion of the kinase domain. Although ΔN-LKB1 is catalytically inactive, it potentiates the stimulating effect of LKB1 on the AMP-activated protein kinase (AMPK) metabolic sensor through a direct interaction with the regulatory autoinhibitory domain of AMPK. In contrast, ΔN-LKB1 negatively interferes with the LKB1 polarizing activity. Finally, combining in vitro and in vivo approaches, we showed that ΔN-LKB1 has an intrinsic oncogenic property. ΔN-LKB1 is expressed solely in the lung cancer cell line, NCI-H460. Silencing of ΔN-LKB1 decreased the survival of NCI-H460 cells and inhibited their tumorigenicity when engrafted in nude mice. In conclusion, we have identified a novel LKB1 isoform that enhances the LKB1-controlled AMPK metabolic activity but inhibits LKB1-induced polarizing activity. Both the LKB1 tumor suppressor gene and the oncogene ΔN-LKB1 are expressed from the same locus and this may account for some of the paradoxical effects of LKB1 during tumorigenesis.
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Proteínas Quinases Ativadas por AMP/metabolismo , Neoplasias Experimentais/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Quinases Proteína-Quinases Ativadas por AMP , Processamento Alternativo , Animais , Domínio Catalítico , Linhagem Celular Tumoral , Humanos , Isoenzimas/química , Isoenzimas/metabolismo , Camundongos , Camundongos Nus , Músculo Esquelético/metabolismo , Miocárdio/metabolismo , Transplante de Neoplasias , Neoplasias Experimentais/patologia , Proteínas Serina-Treonina Quinases/químicaRESUMO
The O (6)-methylguanine-DNA-methyltransferase (MGMT) gene encodes for a DNA repairing enzyme of which silencing by promoter methylation is involved in brain tumorigenesis. MGMT promoter methylation represents a favorable prognostic factor and has been associated with a better response to alkylating agents in glioma and systemic lymphoma. Primary central nervous system lymphoma (PCNSL) is a rare and aggressive extranodal malignant lymphoma. The current standard of care, based on high-dose methotrexate chemotherapy, has improved prognosis but outcome remains poor for a majority of patients. Therapeutic progress in this field is conditioned by limited biological and molecular knowledge about the disease. Temozolomide has recently emerged as an alternative option for PCNSL treatment. We aimed to analyze the MGMT gene methylation status in a series of 24 PCNSLs, to investigate the relationship between methylation status of the gene and immunohistochemical expression of MGMT protein and to evaluate the possible prognostic significance of these biomarkers. Our results confirm that methylation of the MGMT gene and loss of MGMT protein are frequent events in these lymphomas (54 % of our cases) and suggest that they are gender and age related. MGMT methylation showed high correlation with loss of protein expression (concordance correlation coefficient = -0.49; Fisher exact test: p < 0.01), different from what has been observed in other brain tumors. In the subgroup of ten patients who received high dose chemotherapy, the presence of methylated MGMT promoter (n = 4), seems to be associated with a prolonged overall survival (>60 months in three of four patients). The prognostic significance of these molecular markers in PCNSL needs to be further studied in groups of patients treated in a homogeneous way.
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Neoplasias do Sistema Nervoso Central/metabolismo , Linfoma/metabolismo , O(6)-Metilguanina-DNA Metiltransferase/biossíntese , O(6)-Metilguanina-DNA Metiltransferase/genética , Regiões Promotoras Genéticas , Adulto , Idoso , Biomarcadores Tumorais/metabolismo , Neoplasias do Sistema Nervoso Central/genética , Metilação de DNA , Dacarbazina/análogos & derivados , Dacarbazina/uso terapêutico , Feminino , Humanos , Imuno-Histoquímica , Linfoma/genética , Masculino , Pessoa de Meia-Idade , TemozolomidaRESUMO
Y-branch optical waveguides are analyzed in terms of normalized parameters by means of the usual modal analysis. With these parameters the number of variables of the problem is reduced, and universal plots for the mode conversion are obtained. Our results show that the normalized parameters are useful for the design of branching waveguides more tolerant of fabrication errors.
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Several conclusions concerning the applicability of the Lorentzian peak method to compute the complex propagation constant of leaky and lossy waveguide modes are established.
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The propagation characteristics of the leaky modes in planar anisotropic waveguides with a multilayer structure have been investigated by means of a compact rigorous formalism. The leakage losses and leaky transition angle have been studied for the fundamental and first hybrid modes. An inhomogeneous waveguide and buffered step index type structure have been discussed. Particular attention has been devoted to the variation of the loss coefficient of the leaky modes as a function of buffer thickness and buffer refractive index. A notably different behavior has been obtained for various configurations.
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El reflujo gastroesofagico (RGE) es una de las entidades patologicas más frecuentes en la consulta medica general. Por lo tanto, el conocimiento de la entidad corresponde a todo aquel que tenga que ver con la profesion medica. Clinicamente pueden distinguirse dos tipos de RGE: fisiologico y patologico. La presente revision pretende analizar el manejo que actualmente se propone para el RGE de tipo patologico, haciendo enfasis en los metodos diagnosticos principales y en las alternativas quirurgicas de manejo.