NME1 and DCC variants are associated with susceptibility and tumor characteristics in Mexican patients with colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) ranks third in cancer incidence globally and is the second leading cause of cancer-related mortality. The nucleoside diphosphate kinase 1 (NME1) and netrin 1 receptor (DCC) genes have been associated with resistance against tumorigenesis and tumor metastasis. This study investigates the potential association between NME1 (rs34214448 G > T and rs2302254 C > T) and DCC (rs2229080 G > C and rs714 A > G) variants and susceptibility to colorectal cancer development. METHODS: Samples from 232 colorectal cancer patients and 232 healthy blood donors underwent analysis. Variants were identified using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology. Associations were assessed using odds ratios (OR), and the p values were adjusted with Bonferroni test. RESULTS: Individuals carrying the G/T and T/T genotypes for the NME1 rs34214448 variant exhibited a higher susceptibility for develop colorectal cancer (OR = 2.68, 95% CI: 1.76-4.09, P = 0.001 and OR = 2.47, 95% CI: 1.37-4.47, P = 0.001, respectively). These genotypes showed significant associations in patients over 50 years (OR = 2.87, 95% CI: 1.81-4.54, P = 0.001 and OR = 2.99, 95% CI: 1.54-5.79, P = 0.001 respectively) and with early Tumor-Nodule-Metastasis (TNM) stage (P = 0.001), and tumor location in the rectum (P = 0.001). Furthermore, the DCC rs2229080 variant revealed that carriers of the G/C genotype had an increased risk for develop colorectal cancer (OR = 2.00, 95% CI: 1.28-3.11, P = 0.002) and were associated with age over 50 years, sex, and advanced TNM stages (P = 0.001). CONCLUSIONS: These findings suggest that the NME1 rs34214448 and DCC rs2229080 variants play a significant role in colorectal cancer development.

Log odds of positive nodes as a prognostic factor for rectal cancer: a retrospective study

SUMMARY OBJECTIVE: Rectal cancer is an important cause of mortality and morbidity globally. The aim of this study was to investigate whether the log odds of positive nodes system is a better indicator than tumor node metastasis and lymph node ratio systems to determine rectum cancer prognosis, which is an important cause of mortality and morbidity globally. METHODS: This was a single-center retrospective cross-sectional study. Data were obtained from the medical records of patients with rectum adenocarcinoma followed at Gazi University Hospital. The clinicopathological data of 128 patients with rectum adenocarcinoma who underwent low anterior resection or abdominoperineal resection between January 2010 and December 2018 was retrospectively reviewed. Patients with rectum adenocarcinoma as the first and only primary diagnosis, which was confirmed by histopathological examination, than those who had undergone complete curative resection via low anterior resection or abdominoperineal resection were included. Those with familial adenomatous polyposis or Lynch syndrome, those under 18 years of age, with a synchronous tumor, peritoneal spread, or metastatic disease at the time of diagnosis, and those with <12 lymph nodes dissected from the resection material were excluded from the study. RESULTS: In multivariate analysis, age, perineural invasion, tumor node metastasis stage, lymph node ratio stage, and log odds of positive nodes stage were found to be independent prognostic factors (p<0.05). LODDS2 patients' mortality rates were 9.495 times higher than LODDS0 patients [hazard ratio=9.495, (95%CI 4.155-21.694), p<0.001] while LNR2 stage patients' mortality rates were 7.016 times higher than LNR0 stage patients [hazard ratio=7.016, (95%CI 3.123-15.765), p<0.001] and N2 stage patients had a 5.135 times higher risk of mortality than those who were in N0 stage [hazard ratio=5.135 (95%CI 2.451-10.756), p<0.001]. CONCLUSION: Log odds of positive nodes is a more valuable prognostic factor for rectal cancer patients than tumor node metastasis and lymph node ratio systems to determine rectum cancer prognosis.

Functional Variants in MicroRNAs (rs895819, rs11614913 and rs2910164) Are Associated with Susceptibility and Clinicopathological Features in Mexican Patients with Colorectal Cancer.

BACKGROUND: miRNAs are non-coding RNAs participating actively in the post-translational regulation of oncogenes, tumor suppressor, and DNA repair genes implicated in colorectal cancer (CRC). This study aims to examine the association of the variants miR-27a (rs895819 A>G), miR-196a2 (rs11614913 T>G) and miR-146a (rs2910164 C>G) in Mexican CRC patients. METHODS: DNA samples from 183 patients and 186 healthy Mexican subjects were analyzed. Variants were identified by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology. Association was calculated by the odds ratio (OR) and adjusted by the Bonferroni test. RESULTS: Patients carrying the G/G genotype of the rs895819 variant in the miR-27a gene showed an increased risk of CRC (19% vs 12%, P=0.013). A similar tendency was noticed for patients younger than 50 years carrying A/G (48% vs 41%, P=0.014). The A/G genotype in TNM stages I+II (55.7% vs 40.8%, P=0.011) and tumor location in the colon (69.5 vs 40.8%, P=0.001) were also increased. For the variant rs11614913 of the miR-196a2 gene, carriers of the C/C genotype showed an increased risk of CRC (32% vs 22%, P=0.009). This genotype was more frequent in TNM stage III+IV (36.8% vs 22.5%, P=0.007) and the tumor had a more recurrent location in the rectum (31.6% vs 22.5%, P=0.013). The rs2910164 variant of the miR-146a gene was found to have no significant risk associations. CONCLUSION: Our results reveal that the rs895819 variant in miR-27a and rs11614913 in miR-196a2 have a substantial impact on the development of CRC.

The impact of multimodality integrated positron emission tomography-computed tomography on improving the staging and management of head and neck malignancy: a cross- sectional study

ABSTRACT BACKGROUND: Clinical assessment of head and neck cancers is highly challenging owing to the complexity of regional anatomy and wide range of lesions. The diagnostic evaluation includes detailed physical examination, biopsy and imaging modalities for disease extent and staging. Appropriate imaging is done to enable determination of precise tumor extent and involvement of lymph nodes, and detection of distant metastases and second primary tumors. OBJECTIVE: To evaluate the initial staging discrepancy between conventional contrasted computed tomography (CT) and 18F-fluorodeoxy-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) and its impact on management plans for head and neck malignancies. DESIGN AND SETTING: Prospective cross-sectional study in two tertiary-level hospitals. METHODS: This study included 30 patients with primary head and neck malignant tumors who underwent contrasted computed tomography and whole-body 18F-FDG PET/CT assessments. The staging and treatment plans were compared with the incremental information obtained after 18F-FDG PET/CT. RESULTS: 18F-FDG PET/CT was found to raise the stage in 33.3% of the cases and the treatment intent was altered in 43.3% of them, while there was no management change in the remaining 56.7%. 18F-FDG PET/CT had higher sensitivity (96% versus 89.2%) and accuracy (93% versus 86.7%) than conventional contrast-enhanced computed tomography. CONCLUSION: Our study demonstrated that 18F-FDG PET/CT had higher sensitivity and accuracy for detecting head and neck malignancy, in comparison with conventional contrast-enhanced computed tomography. 18F-FDG PET/CT improved the initial staging and substantially impacted the management strategy for head and neck malignancies.

RECK Variants are Associated with Clinicopathological Features and Decreased Susceptibility in Mexican Patients with Colorectal Cancer.

Colorectal cancer (CRC) is the third most common cancer and the second leading cause of death worldwide. Down-regulation of the cysteine-rich reversion-inducing protein with Kazal motifs (RECK) has been confirmed in numerous human cancers and is clinically associated with metastasis. This study aims to explore, for the first time, the possible association of the RECK variants rs11788747 and rs10972727 with CRC susceptibility and clinicopathological features. DNA from 130 CRC patients and 130 healthy blood donors was analyzed. Identification of genetic variants was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology. Association was calculated using the odds ratio (OR) test and P values were adjusted using the Bonferroni test. Individuals carrying the G/G genotype for the rs11788747 variant showed a lower risk of colorectal cancer (OR 0.33; 95% CI 0.16-0.70; P = 0.006). Patients older than 50 years who carry the G/G genotype have a lower risk of CRC (OR 0.26; 95% CI 0.09-0.73; P = 0.019) and of developing advanced tumor-nodule-metastasis (TNM) stages (OR 0.23; 95% CI 0.09-0.54; P = 0.001). Individuals carrying the A/A genotype of the rs10972727 variant also showed decreased risk of CRC (OR 0.38; 95% CI 0.19-0.77; P = 0.011), and were associated with age (over 50 years), sex, advanced TNM stages, and tumor location in the colon. Our results suggest that the RECK variants studied here (rs11788747 and rs10972727) are associated with decreased CRC risk, TNM stages and tumor location.

Impacto de la anestesia intravenosa en cirugía robótica para paciente de alto riesgo sometido a cirugía oncológica de larga duración en el Centro Médico Naval / Impact of intravenous anesthesia in robotic surgery for high-risk patient undergoing long-term oncologic surgery at the Naval Medical Center

Resumen: La práctica de cirugía robótica es un proceso complejo que implica desarrollo y tecnología no sólo en el campo de la cirugía, sino también en el campo de la anestesiología. Implica un proceso multifactorial, ya que ha generado un cambio drástico multidisciplinario basado en tecnología de punta que pretende ofrecer mejores condiciones durante el manejo perioperatorio en cirugía robótica. La anestesia total intravenosa cumple objetivos específicos en relación a la posición del paciente, relajación cerebral, neuroprotección, hemodinamia, pérdida y recuperación de la conciencia, parálisis neuromuscular, parámetros ventilatorios, etc. Ofrece seguridad y calidad al paciente durante el procedimiento con una mínima interferencia con el monitoreo electrofisiológico y permite modular la profundidad anestésica desde una neurosedación hasta una anestesia general, de acuerdo a las diferentes etapas de la cirugía. Un factor atribuible a la anestesia moderna para el éxito de la cirugía robótica es usar diferentes agentes anestésicos que promuevan inducción, mantenimiento y emersión anestésica más rápida y suave, a fin de reducir el tiempo de recuperación del estado de conciencia, funciones básicas y psicomotoras como la anestesia general multimodal.

Abstract: The practice of robotic surgery is a complex process, involving development and technology; not only in the surgery field but also in the anesthesiology field. It implies a multifactorial process since it has generated a drastic multidisciplinary change based on state-of-the-art technology; which aims to offer better conditions during perioperative management in robotic surgery. Intravenous Total Anesthesia accomplishes specific objectives in relation to patient position, brain relaxation, neuroprotection, hemodynamics, loss and recovery of consciousness, neuromuscular paralysis, ventilatory parameters, providing safety and quality during the procedure; with minimal intervention during electrophysiological monitoring and enabling anesthetic depth to be modulated from neurosedation to general anesthesia, according to the different stages of the surgery. A factor attributable to modern anesthesia for robotic surgery success is to employ different anesthetic agents promoting induction, maintenance of general anesthesia, smother and faster anesthetic emersion, for the purpose of reducing recovery time of the state of consciousness), basic and psychomotor functions; as is the general multimodal anesthesia.

Cirugía de urgencia en pacientes con cáncer de colon complicado en Hospital Universitario "General Calixto García" / Emergency Surgery in Patients with Complicated Colon Cancer at General Calixto García University Hospital

Introducción: El cáncer de colon mantiene un importante impacto social y una alta morbilidad a pesar de programas de detección precoz existentes. Ocupa el cuarto lugar entre los tumores malignos y un número importante de pacientes son operados de urgencia por las complicaciones de esta enfermedad, muchas veces desconocida hasta el momento de la cirugía. Objetivo: Caracterizar la cirugía de urgencia realizada a los pacientes con diagnóstico de cáncer de colon complicado. Método: Se realizó un estudio observacional, descriptivo, de corte transversal entre enero de 2014 y diciembre de 2016, en el Servicio de Cirugía General. La muestra fue de 96 pacientes portadores de esta entidad en el Hospital Universitario "General Calixto García". Resultados: Se analizó la incidencia según sexo, relación sexo/localización, relación localización/complicación, estadificación y mortalidad. Prevalecieron los tumores de colon en el sexo femenino y por ende fueron más frecuente las pacientes con complicaciones quirúrgicas por esta entidad en nuestro centro. Predominó la localización derecha globalmente, con predominio femenino. La oclusión intestinal fue la complicación más frecuente. Sobresalió el estadio II según TNM con un 37,5 por ciento y una mortalidad postoperatoria del 31 por ciento. Conclusiones: Nuestros datos coinciden con la tendencia nacional sobre la mayor incidencia del cáncer de colon en pacientes femeninas, son estas las que mayor tasa de morbilidad y mortalidad reportan. Seguir perfeccionando el programa de prevención y detección temprana de la entidad y su tratamiento oportuno causará la reducción de los índices que hoy se exhiben(AU)

Introduction: Colon cancer still has an important social impact and high morbidity despite existing early detection programs. It ranks fourth among malignant tumors, while a significant number of patients undergo emergency surgery for complications of this disease, many times unknown until the time of surgery. Objective: To characterize the emergency surgery performed to patients with a diagnosis of complicated colon cancer. Method: An observational, descriptive, cross-sectional study was carried out, between January 2014 and December 2016, in the general surgery service. The sample consisted of 96 patients with this entity and from General Calixto García University Hospital. Results: The incidence was analyzed according to sex, sex/location relationship, location/complication relationship, staging and mortality. Colon tumors prevailed in the female sex and, therefore, patients with surgical complications from this entity were more frequent in our center. There right location predominated globally, with a predominance in the female sex. Intestinal obstruction was the most frequent complication. Stage two, according to the TNM classification, stood out, accounting for 37.5 percent, together with a postoperative mortality of 31 percent. Conclusions: Our data coincide with the national trend on the highest incidence of colon cancer in female patients, who account for the highest morbidity and mortality rates. Continuing to improve the entity's prevention and early detection program, as well as its timely treatment, will bring about a reduction in the rates nowadays reported(AU)

Automatic Staging of Cancer Tumors Using AIM Image Annotations and Ontologies.

A second opinion about cancer stage is crucial when clinicians assess patient treatment progress. Staging is a process that takes into account description, location, characteristics, and possible metastasis of tumors in a patient. It should follow standards, such as the TNM Classification of Malignant Tumors. However, in clinical practice, the implementation of this process can be tedious and error prone. In order to alleviate these problems, we intend to assist radiologists by providing a second opinion in the evaluation of cancer stage. For doing this, we developed a TNM classifier based on semantic annotations, made by radiologists, using the ePAD tool. It transforms the annotations (stored using the AIM format), using axioms and rules, into AIM4-O ontology instances. From then, it automatically calculates the liver TNM cancer stage. The AIM4-O ontology was developed, as part of this work, to represent annotations in the Web Ontology Language (OWL). A dataset of 51 liver radiology reports with staging data, from NCI's Genomic Data Commons (GDC), were used to evaluate our classifier. When compared with the stages attributed by physicians, the classifier stages had a precision of 85.7% and recall of 81.0%. In addition, 3 radiologists from 2 different institutions manually reviewed a random sample of 4 of the 51 records and agreed with the tool staging. AIM4-O was also evaluated with good results. Our classifier can be integrated into AIM aware imaging tools, such as ePAD, to offer a second opinion about staging as part of the cancer treatment workflow.

Histopathological profile of patients diagnosed with malignant tumors assisted in a hospital of reference of Agreste Pernambucano / Perfil histopatológico de pacientes com diagnóstico de tumores malignos assistidos em um hospital de referência do Agreste Pernambucano

ABSTRACT Cancer is considered a public health problem and is commonly known because of its high mortality rate worldwide. The histopathological evaluation is a fundamental requirement to determine the nature of the lesion, thus it is considered the gold standard examination for diagnosis of neoplasia. The present study aims to evaluate the histopathological profile of patients with malignant tumors diagnosed at a reference hospital in the Agreste Pernambucano. A cross-sectional, descriptive study of a quantitative documentary survey was conducted using the database of the clinical analysis laboratory of the referred Hospital in the field of pathology in the year 2016. A total of 74 cases were selected, and the male gender was the most affected. The age group of patients with the highest prevalence was between 50 and 70 years of age. Clinical characteristics: The most prevalent anatomical location with tumors was both the colon/rectum (30%) and skin (30%). The most common histological type was adenocarcinoma (47.2%). The pathological profile of cancer patients in the region studied were characterized, which served as a database for future epidemiological studies and as a subsidy for the implementation of preventive public policies for the population of this region.

RESUMEN El cáncer es considerado unproblema de salud pública y es comúnmente conocidopor su alta tasa de mortalidad en el mundo. La evaluación histopatológica es fundamental para determinar la naturaleza de la lesión, siendo considerada el examen estándar para el diagnóstico de neoplasias. El objetivo de este trabajo es evaluar el perfil histopatológico de los pacientes diagnosticados con tumor maligno atendidos en un hospital de referencia del Agreste de Pernambuco. Se llevó a cabo un estudio transversal, descriptivo de observación documental de naturaleza cuantitativa, utilizando el banco de datos del laboratorio de análisis clínicos del dicho hospital, en el sector de anatomopatología, en el ano de 2016. Se eligieron 74 casos, siendo el sexo masculino el más afectado. El grupo de edad con mayor prevalencia fue el de 50 a 70 anos. Características clínicas: la ubicación anatómica más frecuente de los tumores fue colon/recto (30%) y piel (30%); el tipo histológico más comúnmente encontrado fue el adenocarcinoma (47,2%). Se caracterizó el perfil patológico de los pacientes con cáncer en la región estudiada, lo que sirvió de base de datos para estudios epidemiológicos futurosy como subsidio a la implementación de políticas públicas preventivas dirigidas a la población de esa región.

RESUMO O câncer é considerado um problema de saúde pública e é comumente conhecido devido ao seu alto índice de mortalidade no mundo. A avaliação histopatológica é fundamental para determinar a natureza da lesão, sendo considerada o exame padrão-ouro para o diagnóstico de neoplasias. O presente trabalho tem como objetivo avaliar o perfil histopatológico dos pacientes com diagnóstico de tumor maligno assistidos em um hospital de referência do Agreste Pernambucano. Foi conduzido um estudo transversal, descritivo de levantamento documental de natureza quantitativa, utilizando o banco de dados do laboratório de análises clínicas do referido hospital, no setor de anatomopatologia, no ano de 2016. Foram selecionados 74 casos, sendo o sexo masculino o mais acometido. A faixa etária de maior prevalência foi dos pacientes entre 50 aos 70 anos de idade. Característica clínicas: a localização anatômica mais prevalente com tumores foi cólon/reto (30%) e pele (30%); o tipo histológico mais comumente encontrado foi adenocarcinoma (47,2%). Caracterizou-se o perfil patológico dos pacientes com câncer na região estudada, o que serviu como base de dados para estudos epidemiológicos futuros e como subsídio para a implementação de políticas públicas preventivas para a população dessa região.

Impact of the updated TNM staging criteria on prediction of persistent disease in a differentiated thyroid carcinoma cohort

ABSTRACT Objective: The 8th TNM system edition (TNM-8) released in 2018 presents significant changes when compared to the 7th edition (TNM-7). The aim of this study was to assess the impact of changing the TNM staging criteria on the outcomes in a Brazilian cohort of differentiated thyroid carcinoma (DTC). Subjects and methods: DTC patients, attending a tertiary, University-based hospital, were classified by TNM-7 and TNM-8. Prediction of disease outcomes status of the two systems was compared in a retrospective cohort study design. Results: Four hundred and nineteen DTC patients were evaluated, comprised by 82% (345/419) women, with mean age at diagnosis of 46.4 ± 15.6 years, 89% (372/419) papillary thyroid carcinoma, with a median tumor size of 2.3 cm (P25-P75, 1.3-3.5). One hundred and sixty patients (38%) had lymph node metastases and 47 (11%) distant metastases at diagnosis. Using the TNM-7 criteria, 236 (56%) patients were classified as Stage I, 50 (12%) as Stage II, 75 (18%) as Stage III and 58 (14%) as Stage IV. When evaluated by the TNM-8, 339 (81%) patients were classified as Stage I, 64 (15%) as Stage II, 2 (0.5%) as Stage III and 14(3%) as Stage IV. After a median follow-up of 4.4years (P25-P75 2.6-6.6), the rate of incomplete biochemical and/or structural response was 54% vs. 92% (P = 0.004) and incomplete structural response was 42% vs. 86% (P = 0.009) for patients classified as stage IV by TNM-7 vs TNM-8, respectively. Only 4 (1%) disease-related deaths were recorded. Conclusions: In our cohort, 37% of DTC patients were down staged with the application of TNM-8 (vs. TNM-7). Additionally, TNM-8 seems to better stratify the risk of structural incomplete response at follow-up.

Cardiac autonomic modulation impairments in advanced breast cancer patients.

AIM: To compare cardiac autonomic modulation in early- versus advanced-stage breast cancer patients before any type of cancer treatment and investigate associated factors. METHODS AND RESULTS: This cross-sectional study included women (30-69 years old) with primary diagnosis of breast cancer and women with benign breast tumors. We evaluated cardiac modulation by heart rate variability and assessed factors of anxiety, depression, physical activity, and other relevant medical variables. Patients were divided into three groups based on TNM staging of cancer severity: early-stage cancer (n = 42), advanced-stage cancer (n = 37), or benign breast tumors to serve as a control (n = 37). We analyzed heart rate variability in time and frequency domains. The advanced-stage cancer group had lower vagal modulation than early-stage and benign groups; also, the advance-stage group had lower overall heart rate variability when compared to benign conditions. Heart rate variability was influenced by age, menopausal status, and BMI. CONCLUSIONS: Heart rate variability seems to be a promising, non-invasive tool for early diagnosis of autonomic dysfunction in breast cancer and detection of cardiovascular impairments at cancer diagnosis. Cardiac autonomic modulation is inversely associated with breast cancer staging.

Revisiting Dukes' paradigm; some node positive colon cancer patients have better prognosis than some node negative patients.

BACKGROUND: The current study tried to evaluate the prognostic value of a modified staging system compared to the American Joint Committee on Cancer (AJCC) staging system for patients with colon cancer. PATIENTS AND METHODS: Surveillance, epidemiology and end results (SEER) database (2004-2014) was queried through SEER*Stat program and AJCC 7th stages were constructed. Through recursive partitioning analysis and subsequent decision tree formation, suggested new stages were formulated based on T and N descriptors. Overall survival analyses were performed through Kaplan-Meier analysis. The cancer-specific Cox regression hazard (adjusted for age, gender, sub-site, grade, race and surgery) was calculated and pair wise comparisons of hazard ratios were conducted. RESULTS: A total of 159,683 non-metastatic patients with colon cancer were recruited in the analysis. Pair wise hazard ratio comparisons among different AJCC 7th stages were conducted and all comparisons were significant (P < 0.0001). However, it should be noted that the adjusted risk of death among stage IIC patients was higher than stage IIIA and IIIB. Pair wise hazard ratio comparisons among different modified system stages were also conducted and all comparisons were significant (P < 0.0001). The outcomes of survival analysis were the same regardless of the number of examined lymph nodes (< 12 vs. ≥ 12). Concordance index (using death from colon cancer as the dependent variable) for AJCC 6th staging system was 0.704 (SE 0.002; 95% CI 0.701-0.708); for AJCC 7th staging system was 0.708 (SE 0.002; 95% CI 0.704-0.711); for Dukes staging system was 0.670 (SE 0.002; 95% CI 0.666-0.674); and for modified staging system was 0.712 (SE 0.002; 95% CI 0.709-0.716). CONCLUSION: The proposed modified staging system provided an improved prognostication for colon cancer patients (particularly for stage II/III disease) compared to AJCC staging system. Further external validation of the proposed staging system is needed before adoption into routine practice.

Expression of anoctamin 1 is associated with advanced tumor stage in patients with non-small cell lung cancer and predicts recurrence after surgery.

PURPOSE: Anoctamin 1 (ANO1), a recently identified calcium-activated chloride channel, has been found to have a critical role in tumorigenesis and tumor progression in several types of cancer. However, its role in non-small cell lung cancer (NSCLC) remains to be elucidated. In this study, we evaluated the utility of ANO1 as a prognostic marker. PATIENTS AND METHODS: ANO1 expression was detected in tumor tissues and paraneoplastic tissues of I-IV stage NSCLC patients who received surgical treatment by using immunohistochemical and quantitative RT-PCR analyses. Epidermal growth factor receptor (EGFR) was investigated using immunohistochemistry. Then the TNM stage of the tumor samples was assessed and patients were followed up for developing recurrence. RESULTS: ANO1 expression was significantly increased in NSCLC tumor tissues compared to the paraneoplastic tissues at both RNA and protein level. In addition, ANO1 overexpression was correlated with the high expression of EGFR and led to an advanced tumor stage. And also high ANO1 expression was significantly correlated with high recurrence rate at 1-year follow-up. CONCLUSIONS: ANO1 overexpression associated with the high expression of EGFR can be a predictive marker of recurrence after surgery in NSCLC patients.

HPV-16 infection modifies overall survival of Puerto Rican HNSCC patients.

BACKGROUND: HPV-16 modifies the overall survival (OS) of patients with oropharyngeal cancer (OPSCC). HPV-16 has been established as risk factor for OPSCC, but HPV-16 infection may also reside in the larynx and oral cavity. We evaluated HPV-16 status on OS of Head and Neck Squamous Cell Carcinoma (HNSCC) patients. METHODS: HPV-16 infection was confirmed by amplification of E6 and E7 viral oncogenes through PCR assay and E6 IHC in 185 HNSCC samples. Associations between HPV-16 status and clinicopathological parameters were performed using Fisher's exact test and x(2). Survival analysis was completed using Kaplan-Meier estimator and multivariate Cox regression analysis. RESULTS: OS of HPV-16 positive patients was longer compared to HPV-16 negative patients (P = 0.002). HPV-16 positive tumors of the larynx (LSCC) and pharynx (PSCC) showed improved OS compared to HPV-16 negative tumors. Also, HPV-16 positive patients exposed to radiotherapy presented a better survival. CONCLUSIONS: HPV-16 status has a positive prognostic value in HNSCC. Addition of HPV-16 status to the TNM staging can provide better assessment in prognosis and guide treatment for HNSCC patients.

Blood preoperative neutrophil-to-lymphocyte ratio is correlated with TNM stage in patients with papillary thyroid cancer

OBJECTIVE: To predict the American Joint Cancer Committee tumor-node-metastasis stage in patients with papillary thyroid carcinoma by evaluating the relationship between the preoperative neutrophil-to-lymphocyte ratio and the tumor-node-metastasis stage. METHODS: We retrospectively examined 161 patients with a diagnosis of papillary thyroid carcinoma. The Neutrophil-to-Lymphocyte Ratio was calculated according to the absolute neutrophil counts and absolute lymphocyte counts on routine blood tests obtained prior to surgery and patients with a Neutrophil-to-Lymphocyte Ratio of 2.0 or more were classified as the high NLR group, while those with a Neutrophil-to-Lymphocyte Ratio less than 2.0 were classified as the low Neutrophil-to-Lymphocyte Ratio group. Clinicopathological variables, which were stratified by the Neutrophil-to-Lymphocyte Ratio, were analyzed. A multivariate analysis was performed to determine factors that affect the Neutrophil-to-Lymphocyte Ratio. The association between the Neutrophil-to-Lymphocyte Ratio and the TNM stage in patients ≥45 years of age was analyzed using the Spearman rank correlation. RESULTS: Various blood indices, including hemoglobin, platelet and thyroid-stimulating hormone levels in the two groups showed no significant differences. Lymph node metastasis, multifocality and tumor size exhibited significant differences in the two groups (p=0.000, p=0.000 and p=0.035, respectively). Correlation analysis indicated that a higher preoperative Neutrophil-to-Lymphocyte Ratio was observed in patients with lymph node metastasis, larger tumor size and multifocality (r=0.341, p=0.000; r=0.271, p=0.000; and r=0.182, p=0.010, respectively). For patients ≥45 years of age, the number of patients with an advanced TNM stage in the high NLR group was higher than that in the low Neutrophil-to-Lymphocyte Ratio group (p=0.013). A linear regression analysis showed that the preoperative Neutrophil-to-Lymphocyte Ratio was positively correlated with the American Joint Cancer Committee tumor-node-metastasis stage (rho=0.403, p=0.000). CONCLUSION: The preoperative Neutrophil-to-Lymphocyte Ratio was closely related to the stage of papillary thyroid carcinoma. The increase in the preoperative Neutrophil-to-Lymphocyte Ratio contributed to the advanced tumor-node-metastasis stage of papillary thyroid carcinoma patients ≥45 years of age.

Tumores carcinoides pulmonares tratados quirúrgicamente valor pronóstico de la 7ª estadificación TNM

Con el objetivo de evaluar el valor pronóstico de la 7a estadificación TNM se analizaron 43 mujeres (61%) y 28 hombres (39%) con diagnóstico de tumor carcinoide tratados quirúrgicamente desde enero/1975 hasta diciembre/2011. Mediana de edad: 38 años (13-67). Presentaron carcinoide típico (CT) 63 (89%) pacientes y 8 (11%) carcinoide atípico (CA). Mediana de seguimiento: 4 años (1 - 24 años). Los estadios correspondientes a CT fueron: IA = 33 (52%), IB = 10 (16%), IIA = 2 (3%), IIB = 2 (3%), IIIA = 12 (19%) y IIIB = 2 (3%); para los CA fueron: IA = 1 (12.5%), IIB = 1 (12.5%), IIIA = 2 (25%) y IIIB = 4 (50%). No hubo diferencia estadísticamente significativa en la supervivencia global a cinco años en el análisis estratificando por estadios (p = 0.689), ni analizando separadamente cada tipo histológico (CT p = 0.547; CA p = 0.592). El intervalo libre de enfermedad fue significativamente menor (CT: 3 años vs CA: 2 años, p = 0.000) y las recaídas más frecuentes en el grupo de carcinoides atípicos (CA: 50% vs CT: 2%, p = 0.000). Los pacientes con CT presentaron buena evolución aun en estadios avanzados, mientras que los que tuvieron CA presentaron menor tiempo de supervivencia e intervalo libre de enfermedad, y mayor frecuencia de recurrencia. El subtipo histológico resultó un factor significativo de pronóstico, mientras que la 7ª estadificación TNM no contribuyó en predecir la supervivencia en los tumores carcinoides.

We analyzed 43 women (61%) and 28 men (39%) surgically treated for carcinoid tumors from Jan/1975 to Dec/2011. Median age: 38 years (13-67). Typical carcinoid (TC) appeared in 63 (89%) patients, 8 (11%) suffered from atypical carcinoid (AC). Median follow-up: 4 years (1-24). TC stages were: IA = 33 (52%), IB = 10 (16%), IIA = 2 (3%), IIB = 2 (3%), IIIA = 12 (19%) and IIIB = 2 (3%); AC stages were: IA = 1 (12.5%), IIB = 1 (12.5%), IIIA = 2 (25%) and IIIB = 4 (50%). TNM classification did not show significant differences on 5-years survival period by stage (p = 0.689), even according to histological type (TC: p = 0.547; AC: p = 0.592). The disease-free survival rate was significantly lower (TC: 3 years vs. AC: 2 years, p = 0.000) and relapses were more frequent in AC (AC: 50% vs. TC: 2%, p = 0.000). The 7th TNM staging was not influential in estimating survival from carcinoid tumours in our population. The histological subtype was a better prognostic factor.

Clinicopathological and immunohistochemical evaluation of oral and oropharyngeal squamous cell carcinoma in Chilean population.

In oral and oropharyngeal squamous cell carcinoma (OCSCC and OPSCC) exist an association between clinical and histopathological parameters with cell proliferation, basal lamina, connective tissue degradation and surrounding stroma markers. We evaluated these associations in Chilean patients. A convenience sample of 37 cases of OCSCC (n=16) and OPSCC (n=21) was analyzed clinically (TNM, clinical stage) and histologically (WHO grade of differentiation, pattern of tumor invasion). We assessed the expression of p53, Ki67, HOXA1, HOXB7, type IV collagen (ColIV) and carcinoma-associated fibroblast (α-SMA-positive cells). Additionally we conducted a univariate/bivariate analysis to assess the relationship of these variables with survival rates. Males were mostly affected (56.2% OCSCC, 76.2% OPSCC). Patients were mainly diagnosed at III/IV clinical stages (68.8% OCSCC, 90.5% OPSCC) with a predominantly infiltrative pattern invasion (62.9% OCSCC, 57.1% OPSCC). Significant association between regional lymph nodes (N) and clinical stage with OCSCC-HOXB7 expression (Chi-Square test P < 0.05) was observed. In OPSCC a statistically significant association exists between p53, Ki67 with gender (Chi-Square test P < 0.05). In OCSCC and OPSCC was statistically significant association between ki67 with HOXA1, HOXB7, and between these last two antigens (Pearson's Correlation test P < 0.05). Furthermore OPSCC-p53 showed significant correlation when it was compared with α-SMA (Kendall's Tau-c test P < 0.05). Only OCSCC-pattern invasion and OPSCC-primary tumor (T) pattern resulted associated with survival at the end of the follow up period (Chi-Square Likelihood Ratio, P < 0.05). Clinical, histological and immunohistochemical features are similar to seen in other countries. Cancer proliferation markers were associated strongly from each other. Our sample highlights prognostic value of T and pattern of invasion, but the conclusions may be limited and should be considered with caution (small sample). Many cases were diagnosed in the advanced stages of the disease, which suggests that the diagnosis of OCSCC and OPSCC is made late.

[Surgically treated bronchopulmonary carcinoid tumours. Prognostic value of TNM staging 7a edition]. / Tumores carcinoides pulmonares tratados quirúrgicamente. Valor pronóstico de la 7a estadificación TNM.

We analyzed 43 women (61%) and 28 men (39%) surgically treated for carcinoid tumors from Jan/1975 to Dec/2011. Median age: 38 years (13-67). Typical carcinoid (TC) appeared in 63 (89%) patients, 8 (11%) suffered from atypical carcinoid (AC). Median follow-up: 4 years (1-24). TC stages were: IA = 33 (52%), IB = 10 (16%), IIA = 2 (3%), IIB = 2 (3%), IIIA = 12 (19%) and IIIB = 2 (3%); AC stages were: IA = 1 (12.5%), IIB = 1 (12.5%), IIIA = 2 (25%) and IIIB = 4 (50%). TNM classification did not show significant differences on 5-years survival period by stage (p = 0.689), even according to histological type (TC: p = 0.547; AC: p = 0.592). The disease-free survival rate was significantly lower (TC: 3 years vs. AC: 2 years, p = 0.000) and relapses were more frequent in AC (AC: 50% vs. TC: 2%, p = 0.000). The 7th TNM staging was not influential in estimating survival from carcinoid tumours in our population. The histological subtype was a better prognostic factor.

Actualización de la estadificación del cáncer de próstata

En nuestro país el cáncer de próstata es la neoplasia más frecuente en hombres de edad avanzada. Por ello, resulta indispensable una adecuada estadificación al momento de establecer la estrategia terapéutica. En este artículo se presenta la 7.a edición del sistema TNM de estadifi cación para el cáncer de próstata, vigente desde el 1.º de enero de 2010. El mismo ha tenido modifi caciones mayores con respecto a la 6.a edición.

In our country prostate cancer is the most common malignancy in older men. An accurate staging is very important to establish treatment strategies.This article presents the 7th edition TNM staging system for prostate cancer, effective January 1, 2010. This has undergone major changes over the 6th edition.

Active site characterization and molecular cloning of Tenebrio molitor midgut trehalase and comments on their insect homologs.

The soluble midgut trehalase from Tenebrio molitor (TmTre1) was purified after several chromatographic steps, resulting in an enzyme with 58 kDa and pH optimum 5.3 (ionizing active groups in the free enzyme: pK(e1) = 3.8 ± 0.2 pK(e2) = 7.4 ± 0.2). The purified enzyme corresponds to the deduced amino acid sequence of a cloned cDNA (TmTre1-cDNA), because a single cDNA coding a soluble trehalase was found in the T. molitor midgut transcriptome. Furthermore, the mass of the protein predicted to be coded by TmTre1-cDNA agrees with that of the purified enzyme. TmTre1 has the essential catalytic groups Asp 315 and Glu 513 and the essential Arg residues R164, R217, R282. Carbodiimide inactivation of the purified enzyme at different pH values reveals an essential carboxyl group with pKa = 3.5 ± 0.3. Phenylglyoxal modified a single Arg residue with pKa = 7.5 ± 0.2, as observed in the soluble trehalase from Spodoptera frugiperda (SfTre1). Diethylpyrocarbonate modified a His residue that resulted in a less active enzyme with pK(e1) changed to 4.8 ± 0.2. In TmTre1 the modified His residue (putatively His 336) is more exposed than the His modified in SfTre1 (putatively His 210) and that affects the ionization of an Arg residue. The architecture of the active site of TmTre1 and SfTre1 is different, as shown by multiple inhibition analysis, the meaning of which demands further research. Trehalase sequences obtained from midgut transcriptomes (pyrosequencing and Illumina data) from 8 insects pertaining to 5 different orders were used in a cladogram, together with other representative sequences. The data suggest that the trehalase gene went duplication and divergence prior to the separation of the paraneopteran and holometabolan orders and that the soluble trehalase derived from the membrane-bound one by losing the C-terminal transmembrane loop.