Curcuma longa extract protects against 5-fluorouracil-induced oral mucositis in hamsters

Abstract Curcumin, contained at Turmeric (Curcumalonga), can exert many beneficial pleiotropic activities in the gastrointestinal tract. This study evaluated the antioxidant and anti-inflammatory activity of C. longa on 5-fluorouracil (5-FU)-induced oral mucositis (OM) in hamsters. Phytochemical analysis of crude C. longa extract (CLE) was performed to detect the presence of curcumin by TLC and HPLC. Golden Syrian hamsters were orally pre-treated with CLE (5, 50, or 100mg/kg). Cheek pouch samples were subjected to macroscopic and histopathological evaluation. ELISA was performed to quantify the inflammatory cytokines IL-1ß and TNF-α. Superoxide dismutase (SOD), glutathione (GSH) and malondialdehyde (MDA) levels were assessed by ultraviolet-visible spectroscopy analysis. Behavior analysis was conducted by the open field test. Curcumin content in the CLE was 0.55%m/m ± 0.0161 (2.84%). The group treated with 5mg/kg CLE showed healing evidence with macroscopic absence of ulceration (p<0.05) and microscopic aspect of re-epithelialization, discrete inflammatory infiltrate and absence of edema. Treatment with 5mg/kg CLE significantly increased GSH levels, and reduced MDA levels and SOD activity (p˂0.05), and decreased IL-1ß (p˂0.05) and TNF-α (p˂0.01) levels. A significant reduction in walking distance, ambulation, speed, and rearing was observed for motor activity. Curcumin reduced oxidative stress, inflammation, and motor activity in hamsters with 5-FU-induced OM.

Gene expression and apoptosis response in hepatocellular carcinoma cells induced by biocompatible polymer/magnetic nanoparticles containing 5-fluorouracil

BACKGROUND: Super-paramagnetic iron oxide nanoparticles (SPION) contain a chemotherapeutic drug and are regarded as a promising technique for improving targeted delivery into cancer cells. RESULTS: In this study, the fabrication of 5-fluorouracil (5-FU) was investigated with loaded Dextran (DEXSPION) using the co-precipitation technique and conjugated by folate (FA). These nanoparticles (NPs) were employed as carriers and anticancer compounds against liver cancer cells in vitro. Structural, magnetic, morphological characterization, size, and drug loading activities of the obtained FA-DEX-5-FUSPION NPs were checked using FTIR, VSM, FESEM, TEM, DLS, and zeta potential techniques. The cellular toxicity effect of FA-DEX-5-FU-SPION NPs was evaluated using the MTT test on liver cancer (SNU-423) and healthy cells (LO2). Furthermore, the apoptosis measurement and the expression levels of NF-1, Her-2/neu, c-Raf-1, and Wnt-1 genes were evaluated post-treatment using flow cytometry and RT-PCR, respectively. The obtained NPs were spherical with a suitable dispersity without noticeable aggregation. The size of the NPs, polydispersity, and zeta were 74 ± 13 nm, 0.080 and 45 mV, respectively. The results of the encapsulation efficiency of the nano-compound showed highly colloidal stability and proper drug maintenance. The results indicated that FA-DEX-5-FU-SPION demonstrated a sustained release profile of 5-FU in both phosphate and citrate buffer solutions separately, with higher cytotoxicity against SNU-423 cells than against other cells types. These findings suggest that FA-DEX-SPION NPs exert synergistic effects for targeting intracellular delivery of 5-FU, apoptosis induction, and gene expression stimulation. CONCLUSIONS: The findings proved that FA-DEX-5-FU-SPION presented remarkable antitumor properties; no adverse subsequences were revealed against normal cells.

Bomba elastomérica, aplicación de citostáticos en hospital de día oncológico / Elastomeric pump, application of cytostatics

Introducción. Este espacio es acerca del empleo de bombas elastoméricas en la administración de citostáticos de infusión continua con pacientes oncológicos que reciben tratamiento endovenoso, de infusión continua en el domicilio, mejorando así la calidad de vida del paciente, (esta experiencia es sólo en relación a aplicación de 5 fluorouracilo).Material y método: Al inicio, la primera dosis de quimioterapia, se realiza en el internado común para observar la tolerancia a la medicación, y en la segunda o tercera aplicación se realiza la misma en el hospital de día la primera parte del esquema, y luego se realiza la conexión de la bomba elastomérica que infundirá durante 46hs con el 5 fluorouracilo. El paciente asistirá al hospital oncológico para realizar la desconexión. Nuestro rol enfermero de contención y capacitación es necesario y así poder asegurar el buen manejo del dispositivo y brindar seguridad a los pacientes, para que logren un cuidado autónomo, seguro y eficaz. Para tal fin se les provee un instructivo. Poseer catéter implantable es requisito obligatorio para esta modalidad. Beneficios encontrados: es portátil y ergonómico, Mejora la movilidad y autocuidado, tasa de infusión exacta. Características de seguridad, que incluyan la protección del reservorio frente a posibles daños; Descomprimimos las internaciones, reducimos la espera de camas para internación de pacientes. Reducimos el uso de bombas comunes eléctricas del internado quedando a disponibilidad para otros pacientes hospitalizados. Dificultades halladas: Desconocimiento del paciente sobre el insumo (bomba). Inseguridad del paciente al encontrarse en el hogar por primera vez. Trámites burocráticos para autorización de la bomba. Conclusión: esta implementación innovadora requiere aún más aprendizaje, contamos con el apoyo del Departamento de Enfermería y la jefatura del servicio del Hospital de Día Oncológico, para el uso de las bombas. Para esta experiencia se utilizaron 10 bombas elastoméricas. Experiencia práctica, positiva para el paciente, además él mismo se compromete con su autocuidado y tratamiento, se logra evitar las exposiciones nosocomiales minimizando así los riesgos de contagios. Reducimos el uso de bombas comunes eléctricas del internado quedando a disposición para otros pacientes que lo requieran. Descomprimimos el internado común permitiendo así contar con más camas y mayor fluidez para satisfacer la demanda de internación de pacientes con otras patologías[AU]

Introduction. This space is about the use of elastomeric pumps in the administration of cytostatics of continuous infusion with cancer patients who receive intravenous treatment, of continuous infusion of qmt at home, thus improving the quality of life of the patient, (this experience is only in relation to to application of 5 fluorouracil). Material and method: At the beginning, the first dose of chemotherapy is carried out in the common boarding school to observe the tolerance to the medication, and in the second or third application it is carried out in the day hospital the first part of the scheme, and then the elastomeric pump is connected, which will infuse for 46 hours with 5 fluorouracil. The patient will attend the cancer hospital at hour 46 to perform the disconnection. Our nursing role of containment and training is necessary in order to ensure the proper handling of the device and provide safety to patients, so that they achieve autonomous, safe and effective care. For this purpose, an instruction manual is provided. Having an implantable catheter is a mandatory requirement for this modality; Benefits found: It is portable and ergonomic, Improves mobility and self-care, exact infusion rate. Safety features, including protection of the reservoir against possible damage; We decompressed hospitalizations, we reduced the wait for beds for patient admission. We reduced the use of common electric pumps in the internship, making them available for other hospitalized patients. Difficulties encountered: Lack of knowledge of the patient about the input (pump). Patient insecurity when being at home for the first time. Bureaucratic procedures for authorization of the pump. Conclusion. This innovative implementation requires even more learning, we have the support of the Nursing Department and the head of the Oncology Day Hospital service, for the use of the pumps. For this experiment 10 elastomeric pumps were used. Practical experience, positive for the patient, he also commits himself to self-care and treatment, it is possible to avoid nosocomial exposures, thus minimizing the risks of contagion. We reduce the use of common electric pumps in the internship by being available for other patients who require it. We decompress the common boarding school, thus allowing us to have more beds and greater fluidity to satisfy the demand for hospitalization of patients with other pathologies[AU]

Introdução. Este espaço trata da utilização de bombas elastoméricas na administração de citostáticos de infusão contínua em pacientes oncológicos que recebem tratamento intravenoso, de infusão contínua de qmtem casa, melhorando assim a qualidade de vida do paciente, (esta experiência é apenas emrelação a aplicação de 5 fluorouracil). Material e método: No início, a primeira dose de quimioterapia é realizada no colégio interno comum para observar a tolerânciaao medicamento, e na segunda ou terceira aplicação é realizada em hospital dia a primeira parte do esquema, e em seguida, a bomba elastomérica é conectada, que fará a infusão de 5 fluorouracil por 46 horas. O paciente comparecerá ao hospital oncológico na hora 46 para realizar o desligamento. Nosso papel de enfermagem de contenção e treinamento é necessário a fim de garantir o correto manuseio do dispositivo e dar segurançaaos pacientes, para que alcancem um cuidado autônomo, seguro e eficaz. Para tal, é fornecido um manual de instruções. Ter Um catéter implantável é requisito obrigatório para esta modalidade; Benefícios encontrados: É portátil e ergonômico, melhora a mobilidade e o autocuidado, taxa de infusão exata. Recursos de segurança, incluindo proteção do reservatório contra possíveis danos; Descomprimimos internações, reduzimos a espera por leitos para admissão de pacientes .Reduzimos o uso de bombas elétricas comuns no internato, disponibilizando-as para outros pacientes internados. Dificuldades encontradas: Falta de conhecimento do paciente sobre o insumo (bomba). Insegurança do paciente ao estar em casa pela primeira vez. Procedimentos burocráticos para autorização da bomba. Conclusão. Esta implementação inovadora exige ainda mais aprendizagem, contamos com o apoio do Departamento de Enfermagem e do chefe do serviço de Oncologia-Dia Hospital, para utilização das bombas. Para esta experiencia foram utilizadas 10 bombas elastoméricas. Experiência prática, positiva para o paciente, ele também se compromete com o autocuidado e o tratamento, sendo possível evitar exposições nosocomiais, minimizando assim os riscos de contágio. Reduzimos o uso de bombas elétricas comuns no estágio, disponibilizando para outros pacientes que necessitem. Descomprimimos o internato comum, permitindo assim ter Mais leitos e maior fluidez para atender a demanda de internação de pacientes como utras patologias[AU]

Effect of FOLFOX6 chemotherapy on serum VEGF expression in advanced colorectal cancer patients

SUMMARY OBJECTIVE: To explore the effect of FOLFOX6 chemotherapy on serum vascular endothelial growth factor (VEGF) expression in advanced colorectal cancer patients. METHODS: A retrospective analysis of 81 patients with advanced colorectal cancer who visited our hospital from March 2014 to February 2016 was performed. All the patients were treated with FOLFOX6 chemotherapy. On day 1, patients received oxaliplatin 100 mg/m2 ivgtt (2h), calcium folinate 200 mg/m2 ivgtt (2h), 5 fluorouracil 400 mg/m2 iv bolus and 5 fluorouracil 2500 mg/m2 ivgtt (5h). The treatment course was 2 weeks, and 4 treatment courses were required. The changes in the levels of VEGF and CRP and quality of life before and after 4 courses of chemotherapy were observed and therapeutic effects and adverse reactions after chemotherapy were evaluated. RESULTS: After treatment, the total efficiency of chemotherapy was 82.72% (67/81) with 24 cases in complete remission, 25 cases in partial response, 18 cases in stable disease and 14 cases in progressive disease. The levels of CRP and VEGF after the treatment were significantly lower than those before treatment (5.69±0.77) mg/L vs. (7.99±1.36) mg/L; (443.26±21.55) pg/mL vs. (542.83±20.44) pg/mL] (P<0.05). The KPS grade after treatment was significantly higher than that before treatment (57.84±4.6) point vs. (50.99±3.73) point] (P<0.05). Among them, 3 cases developed a rash, 5 cases experienced hair loss, and 9 cases developed nausea and vomiting. CONCLUSION: FOLFOX6 chemotherapy can decrease serum VEGF expression in patients with advanced colorectal cancer and enhance the curative effect with high safety, which is good for the improvement of patients' survival.

RESUMO OBJETIVO: Explorar o efeito da quimioterapia Folfox6 na expressão do fator de crescimento endotelial vascular sérico (VEGF) em pacientes com câncer colorretal avançado. MÉTODOS: Uma análise retrospectiva de 81 pacientes com câncer colorretal avançado que visitaram nosso hospital de março de 2014 a fevereiro de 2016 foi realizada. Todos os pacientes foram tratados com quimioterapia Folfox6. No dia 1, os doentes receberam oxaliplatina 100 mg / m2 ivgtt (2h), folinato de cálcio 200 mg/m2 ivgtt (2h), 5 fluorouracil 400 mg/m2 iv bolus e 5 fluorouracil 2.500 mg/m2 ivgtt (5h). O curso de tratamento foi de duas semanas e foram necessários quatro cursos de tratamento. Foram observadas as alterações nos níveis de VEGF e CRP e qualidade de vida antes e após quatro cursos de quimioterapia e avaliados os efeitos terapêuticos e reações adversas após a quimioterapia. RESULTADOS: Após o tratamento, a eficácia total da quimioterapia foi de 82,72% (67/81), com 24 casos em remissão completa, 25 casos em resposta parcial, 18 casos em doença estável e 14 casos em doença progressiva. Os níveis de CRP e VEGF após o tratamento foram significativamente inferiores aos do tratamento (5,69 ± 0,77) mg / L vs. (7,99 ± 1,36) mg / L; (443,26 ± 21,55) pg / mL vs. (542,83 ± 20,44) pg / mL] (P < 0,05). O grau de KPS após o tratamento foi significativamente maior do que antes do tratamento (57,84 ± 4,6 pontos) vs. (50,99 ± 3,73 pontos)] (P < 0,05). Entre eles, três casos desenvolveram erupção cutânea, cinco casos sofreram perda de cabelo e nove casos desenvolveram náuseas e vômitos. CONCLUSÃO: A quimioterapia Folfox6 pode, obviamente, diminuir a expressão de VEGF no soro em pacientes com câncer colorretal avançado e melhorar o efeito curativo com alta segurança, o que é bom para a melhoria da sobrevivência dos pacientes.

Experience in intra-arterial chemotherapy using two protocols for the treatment of OSCC over two decades at the University Hospital Vienna

OBJECTIVES: This retrospective study performed a comprehensive analysis of the usage of intra-arterial chemotherapy (iaCh) for locally recurrent UICC stage IV oral squamous cell carcinoma (OSCC) over two decades at the Department of Cranio-Maxillofacial and Oral Surgery at the University Hospital Vienna to assess the utility of its future use. METHODS: Between 1994 and 2014, iaCh was indicated in 48 OSCC cases. In these, the two most frequent iaCh schemes, cisplatin/5-fluorouracil (Cis/5-FU) and methotrexate/bleomycin (MTX/Bleo), were chosen for further analysis. The effect on survival of two distinct intra-arterial protocols and their covariates were analyzed with the Kaplan-Meier method as well as univariate and multivariate Cox proportional hazard regression models. RESULTS: The mean follow-up period was 29.91 months. The two intra-arterial chemotherapy groups did not differ significantly in sample size, demographic data or therapeutic covariates. The Cis/5-FU iaCh regimen was associated with significantly better overall survival (median OS 2.6 years vs. 1.3 years; p=0.002) and had a beneficial effect on survival (HR=3.62, p=0.015). Side effects occurred at a frequency similar to that described in the literature for intravenous chemotherapy (ivCh). CONCLUSIONS: These results suggest a preference for administering Cis/5-FU for iaCh. Nevertheless, due to economic considerations in healthcare expenditures, there is no future for iaCh in the treatment of head and neck carcinomas because ivCh is known to be equivalent.

¿Es la mitomicina C superior al 5-fluorouracilo como antimetabolito en la trabeculectomía para el glaucoma? / Is mytomicyn better than 5-fluorouracil as antimetabolite in trabeculectomy for glaucoma?

INTRODUCCIÓN: La trabeculectomía es considerada la intervención de elección en pacientes con glaucoma con indicación de manejo quirúrgico. Dentro de los factores asociados al fracaso de este tratamiento se encuentra la cicatrización postoperatoria. Para disminuir este factor se han usado distintos antimetabolitos, en particular el 5-fluorouracilo y la mitomicina C. Si bien ambos se consideran efectivos, no está claro si existen diferencias entre ambos en relación al éxito de la trabeculectomía y los efectos adversos. MÉTODOS: Para responder esta pregunta utilizamos Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud, la cual es mantenida mediante búsquedas en múltiples fuentes de información, incluyendo MEDLINE, EMBASE, Cochrane, entre otras. Extrajimos los datos desde las revisiones identificadas, reanalizamos los datos de los estudios primarios, realizamos un metanálisis, preparamos tablas de resumen de los resultados utilizando el método GRADE. RESULTADOS Y CONCLUSIONES: Identificamos cuatro revisiones sistemáticas que en conjunto incluyen 17 estudios primarios, de los cuales, 12 corresponden a ensayos aleatorizados. Concluimos que el uso de mitomicina C podría lograr una mayor disminución de la presión intraocular e incrementar la tasa de éxito calificado en comparación con el 5-fluorouracilo. Sin embargo, su uso podría asociarse a una mayor incidencia de complicaciones.

INTRODUCTION: Trabeculectomy is considered the standard for glaucoma surgery. Postoperative scarring is one the factors associated with surgery failure. Different antimetabolites have been used in order to reduce this risk, particularly 5-fluorouracil and mitomycin C. Although both are considered effective, it is not clear if they are different in terms of success of trabeculectomy and adverse effects. METHODS: To answer this question we used Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies, conducted a meta-analysis and generated a summary of findings table using the GRADE approach. RESULTS AND CONCLUSIONS: We identified four systematic reviews including 17 studies overall, of which 12 were randomized trials. We concluded mitomycin C might be more effective in reducing intraocular pressure and increasing qualified success compared to 5-fluorouracil. However, its use might be associated to a higher risk of complications.

Respuesta histológica completa a la neoadyuvancia en carcinoma gástrico avanzado: A propósito de un caso y revisión de la literatura / Histological complete response to neoadjuvant therapy in advanced gastric carcinoma: A case report and review of literature

La presente comunicación, describe el primer caso en el Instituto Regional de Enfermedades Neoplásicas "Luis Pinillos Ganoza" IREN Norte en la que una paciente con carcinoma gástrico avanzado ha mostrado respuesta histopatológica completa a neoadyuvancia. Se presenta una paciente mujer de 70 años con diagnóstico histopatológico de adenocarcinoma gástrico tubular moderadamente diferenciado, localmente avanzado con imágenes de adenopatías perigástricas asociadas y pérdida de la interfase entre tumoración gástrica, hilio hepático y vesícula biliar. Luego de 6 cursos de quimioterapia neoadyuvante con esquema FOLFOX - 4 al 80%, se obtiene una respuesta casi completa desde el punto de vista tomográfico; por ello a la paciente se le realiza gastrectomía subtotal distal más linfadenectomía D2 más gastroyeyunoanastomosis Billroth II término lateral tipo Hofmeister Finsterer, verificándose, al examen microscópico de la pieza operatoria, sólo gastritis crónica y aguda con áreas mucosas y cambios reactivos. No se observa neoplasia maligna viable. Ganglios linfáticos: 0/33. Paciente evoluciona favorablemente. A propósito del caso se hace una revisión de la literatura médica relevante actualizada

This communication describes the first case in the Regional Institute of Neoplastic Diseases "Luis Pinillos Ganoza" IREN North in which a patient with advanced gastric carcinoma showed complete response to neoadjuvant histopathologic. We describe the case of a patient woman of 70 years old with histopathologic diagnosis of moderately differentiated tubular gastric adenocarcinoma, locally advanced associated with images of perigastric lymphadenopathy and loss of the interface between gastric tumor, hepatic hilum and gallbladder. After 6 courses of neoadjuvant chemotherapy with FOLFOX scheme - 4 to 80%, an almost complete response from the point of tomographic view is obtained, so the patient is underwent to distal subtotal gastrectomy lymphadenectomy D2 more gastrojejunoanastomosis Billroth II termino lateral type Hofmeister Finsterer verifying on microscopic examination of surgical specimen only acute and chronic gastritis with mucous areas and reactive changes. No feasible malignancy is observed. Lymph nodes: 0/33. Commenting on the case, a review of recent relevant literature is realized

Eficacia y seguridad de bevacizumab en combinación con quimioterapia folfiri en el tratamiento de segunda línea para pacientes con diagnostico de cáncer colorrectal metastásico / Efficacy and safety of bevacizumab in combination with folinic chemotherapy in second-line treatment for patients diagnosed with metastatic colorectal cancer

INTRODUCCIÓN: Antecedentes: El presente dictamen expone la evaluación de la eficacia y seguridad del uso de bevacizumab en combinación con quimioterapia FOLFIRI como tratamiento de segunda línea para pacientes de segunda línea para pacientes para pacientes con diagnóstico de cáncer colorrectal metastásico. Aspectos Generales: El cáncer colorrectal es uno de los cánceres más frecuentes a nivel mundial. Anualmente se reportan más de 1.361 millones de nuevos casos y 694.000 muertes por cáncer colorrectal constituyéndose en la tercera cuasa más frecuente de cáncer y en la cuarta causa de muerte a nivel mundial. Aproximadamente, uns 20-55% de los pacientes con cácner colorrectal presentan enfermedad metastásica al momento del diagnóstico, mientras que u 50-60% de los pacientes diagnosticados en estadios tempranos, pese a ser tratados quirúrgicamente igual desarrollarán metástasis, mayormente de localización hepática. Debido a ello, el prognóstico de los pacientes con cáncer colorrectal metastásico o recurrente en general es pobre, asociándose a una sobrevida global a los 5 años del 50%.Tecnología Sanitaria de Interés: Bevacizumab es un anticuerpo monoclonal específico contra el factor de crecimiento del endotelio vascular (VEGF) por sus siglas en inglés) humano. Al ligarse al VEGF, específicamente al VEGFp-A, actúa como una citoquina antiangiogénica previendo su interacción con los receptores del VEGFE-1 and VEGFR-2), mediando la inhibición del crecimiento y mantenimiento de los vasos sanguíneos de una variedad de células tumorales. METODOLOGIA: Estrategia de Búsqueda: Se realizó una búsqueda de la literatura con respecto a la eficacia y seguridad de bevacizumab en combinación con esquema de quimioterapia FOLFIRI como tratamiento de esegunda línea para pacientes con cáncer colorrectal metastásico. Las seguientes fuentes han sido revisadas y consultadas con la intención de buscar la mejor evidencia disponible que directamente responda a la pregunta PICO de esta evaluación. METODOLOGÍA: Sinopsis de la Evidencia: Se realizó la busqueda bibliográfica y de evidencia cientifica hasta diciembre 2016 para el sustento de uso de bevacizumab en combinación con el esquema de quimioterapia FOLFIRI como tratamiento de segunda línea para pacientes con diagnóstico de cáncer colocrrectal metastásico que hubieran recibido previamente quimioterapia a base de oxaliplatino. Se presenta la evidencia disponible según el tipo de publicación priorizada en los criterios de inclusión. CONCLUSIONES: El presente dictamen se evaluó la evidencia científica publicada hasta diciembre de 2016 en relación al uso de bevacizumab en combinación con quimioterapia FOLFIRI como una alternativa de tratamiento de segunda línea más eficaz y segura que la quimioterapia FOLFIRI, en pacientes con cácner colocrrectal metastásico que han progresado a quimioterapia a base de oxaliplatino. La mejor evidencia disponible a la fecha no permite evaluar el uso de bevacizumab más quimioterapia FOLFIRI, en comparación a quimioterapia FOLFIRI sin bevacizumab en pacientes que han progresado a regímenes de quimioterapia a base de oxaliplatino sin bevacizumab. Adicionalmente, en el Petitorio Farmacológico de EsSalud existen otras alternativas de tratamiento quimioterapéutico disponibles para pacientes que han progresado a regímenes a base de oxaliplatino, tales como irinotecán y FOLFIRI, las cuales también son considerados opciones de tratamiento de segunda línea en las GPC internacionales. Por lo expuesto, el Instituto de Evaluación de Tecnologías en Salud e Investigación (IETSI) no aprueba el uso de bevacizumab en combinación en quimioterapia FOLFIRI para el tratamiento de cáncer colorrectal metastásico en pacientes que han progresado a quimioterapia a base de oxaliplatino.

Eficacia y seguridad de la adición de panitumumab a folfox o folfiri como tratamiento de primera línea en pacientes con cancer colrectal metastásico con gen kras no mutado (wild type) e irresecable / Efficacy and safety of the addition of panitumumab to folfox or folfiri as first-line treatment in patients with metastatic col- rectal cancer with non-mutated (wild type) kras gene and unresectable

INTRODUCCIÓN: Antecedentes: El presente dictamen expone la evaluación de tecnología de la eficacia y seguridad del uso de panitumumab asociado a quimioterapia como primera línea de tratamiento de cácner colorrectal metastásico. Aspectos Generales: El cáncer colorrectal es la segunda causa de muerte por cáncer en los países occidentales. Al momento del diagnóstico, alrededor del 20-25% de los pacientes presentan cáncer colorrectal metastásico (CCRm), mientras que se estima que entre el 20 y el 35% lo desarrollará durante el curso de la enfermedad. Además, entre el 80% y el 90% de los casos de CCRm son irresecables. A pesar de los avances en el tratamiento del CCRm, el propósito aún es pobre, con una tasa de sobrevida a los 5 años que varía entre el 10% al 20%. Tecnología Sanitaria de Interés: Panitumumab, es un anticuerpo monoclonal recombinante totalmente humano IgG2, que se une con gran afinidad y especialidad al EGFR humano. El EGFR es una glicoproteína transmembrana que pertenece a una subfamilia de receptores de las tirosinas quinasas de tipo I, que incluye el EGFR (HER1/c-ErbB-1), HER2, HER3, HER4. El EGFR potencia el crecimiento celular en tejidos epiteliales normales, incluidos la piel y los folículos pilosos, y se expresa en una variedad de células tumorales. La unión panitumumab al EGFR provoca la internalización del receptor, la inhibición del crecimiento celular, la inducción de la apoptosis y un descenso en la producción de interleuquina 8 y del factor de crecimiento del endotelio vascular. El EGFR juega un rol importante en el desarrollo de CCR, por lo que su inhibición podría dar la impresión de ser una estrategia prometedora de tratamiento para CCRm. METODOLOGIA: Estrategia de Búsqueda: Se llevó a cabo una búsqueda sistematica de la literatura con respecto a la eficacia y seguridad de la adición de panitumumab a FOLFOX o FOLFIRI comparado con FOLFOX o FOLFIRI, para el tratamiento de cáncer colorrectal metastásico, irresecable, KRAS no mutado, ECOG-2. La búsqueda s einició revisando la inforamción sobre el uso del medicamiento de acuerdo con entidades reguladoras como la Food and Drug Administration (FDA), la European Medicines Agency (EMA) y la Dirección General de Medicamentos y Drogas (DIGEMID). Posteriormente, se revisaron las bases de datos de Pubmed, TRIPDATABASE y www.clinicals.gov. Adicionalmente, se realizó una búsqueda de evaluaciones de tecnologías y guías de práctica clínica en las páginas web de grupos dedicados a la investigación y educación en salud en general como The National Institute for Helath and Care Excelence (NICE), Scottish Intercollegiate Guidelines Network (SIGN), National Comprehensive Cancer Network (NCCN), y The Cochrane Collaboration. RESULTADOS: Sinopsis de la Eidenci: Se llevó a cabo una búsqueda de evidencia científica relacionada al uso de panitumumab asociado a quimioterapia para el tratamiento de CCRm irresecable, KRAS no mutado. CONCLUSIONES: El tratamiento para el CCRm recomendado consiste en quimioterapia sistémica con FOLFOX, FOLFIRI o XELOX, todos los cuales se encuentran disponibles en el Petitorio Farmacológico de EsSalud. De acuerdo a las GPC revisadas, la adición de panitumumab a quimioterapia es opcional y condicionada a la ausencia de mutaciones KRAS y de la ubicación de las lesiones en el lado izquierdo. La evidencia evaluada en relación a la adición de panitumumab a FOLFOX en comparación con FOLFOX solo, no muestra benefícios en términos de aumento de la sobrevida global ni de la calidad de vida. Los benefícios en términos de SLP mostrados en el dictamen son modestos y provienen de análisis de subgrupos en que se ha perdido la aleatorización. La evidencia econtrada en relación a la adición de panitumumab a FOLFIRI en comparación con FOLFIRI solo, no pudo ser considerada para el presente dictamen por que proviene de estudios fase II, sin brazo comparador. La adición de panitumumab a quimioterapia presenta una incidencia alta de toxicidad dermatológica (>90%), con un 34 % d eEA dermatológicos grado 3 y menos de 1% de EA dermatológicos grado 5. Asismismo, la incidencia de eventos adversos no dermatológicos grado 3 o 4 fue del 82% y de eventos adversos serios fue de 40%. Así, la relación riesgo benefício no es clara, por lo que, no se encontraron argumentos técnicos que justifiquen la adición de panitumumab a la quimioterapia sistémica (FOLFOX o FOLFIRI) como primera línea de tratamiento para cpancer colorrectal irresecable, KRAS no mtado. El Instituto de Evaluación de Tecnologías en Salud-IETSI, no aprueba la adición de panitumumab a quimioterapia a base de FOLFOX o FOLFIRI como tratamiento de primera línea para cáncer colorrectal metastásico, irresecable, KRAS no mutado.

Infección genital masculina por virus de papiloma humano / Male genital infection by human papiloma virus

El virus del papiloma humano (VPH) es una de las enfermedades de transmisión sexual más comunes. Puede afectar tanto el aparato genital masculino y femenino, como también el área perianal, ano, y diversas áreas de cabeza y cuello y otorrinolaringológicas, ya sea como lesiones benignas o como promotor de lesiones malignas. Las lesiones benignas por VPH en genitales masculinos se caracterizan fundamentalmente por la aparición de lesiones verrugosas, aunque también puede manifestarse mediante lesiones planas atípicas. En algunos casos hay ausencia de lesiones macroscópicamente visibles que pueden hacerse evidentes con la prueba de ácido acético. La biopsia de la lesión, su evaluación anatomopatológica y, sobre todo, la determinación de la existencia y el tipo de virus involucrado mediante PCR (reacción en cadena de la polimerasa) permiten confirmar el diagnóstico. En algunas ocasiones es necesario realizar una cistoscopia para diagnosticar lesiones intrauretrales y vesicales. Los tratamientos propuestos son muy variados y de eficacia dispar, desde las topicaciones y la electrocirugía o la criocirugía, hasta el empleo de la tecnología láser. La prevención con el uso de protección durante el acto sexual así como la educación sexual son fundamentales. En los últimos 10 años se ha implementado el uso de la vacuna para el VPH en niñas con el fin de disminuir la incidencia de lesiones de alto grado y de cáncer de cuello uterino, pero su indicación en varones es menos clara y aún no ha sido consensuada. (AU)

Human papiloma virus (HPV) is one of the most common sexual transmitted diseases. It can affect the male genitalia, as well as the perianal and anal regions and multiple areas of the head and neck and otorhinolaryngological structures, as benign lesiones or as a promoter of malignant lesions. Benign male genitalia lesions are characterized mainly by verrucous lesions, although flat atypical lesions can be found, as well as the abscence of macroscopic visible lesions that in some cases can become evident using the acetic acid test. Lesion biopsy, its histological evaluation, and the determination of the existence and type of virus using PCR (Polymerase Chain Reaction) can confirm the diagnosis. In some cases is necessary to do a cistoscopy to diagnose intraurethral and vesical lesions. Proposed treatments are varied and with a wide range of efficacy, from topications to electro or cryosurgery, and the use of laser technology. Sexual education and the use of sexual protection are essential in prevention. In the last 10 years the use of VPH vaccine in girls was widely spread, in order to decrease the incidence of high grade lesions and cervix cancer. Its indication in male patients is less clear and not yet consented among specialists. (AU)

Erythroplasia of Queyrat treated with topical 5-fluorouracil

Abstract We report a 33-year-old male patient diagnosed with erythroplasia of Queyrat. The patient had an erythematous and eroded lesion affecting more than 50% of the glans associated with bleeding and local pain. Despite previous indication of penectomy, he was successfully treated with topical 5-fluorouracil.

Beneficio de la quimioterapia adyuvante en pacientes con cáncer de colon: cohorte retrospectiva de un hospital clínico universitario / Benefit of adjuvant 5-fluorouracil based chemotherapy for colon cancer: a retrospective cohort study

Background: Multiple clinical trials have demonstrated the benefits of adjuvant 5-fluorouracil-based chemotherapy for patients with resectable colon cancer (CC), especially in stage III. Aim: To describe the clinical characteristics of a cohort of CC patients treated at a single university hospital in Chile since 2002, and to investigate if chemotherapy had an effect on survival rates. Material and Methods: Review of a tumor registry of the hospital. Medical records of patients with CC treated between 2002 and 2012 were reviewed. Death certificates from the National Identification Service were used to determine mortality. Overall survival was described using the Kaplan-Meier method. A multivariate Cox proportional hazard regression model was also used. Results: A total of 370 patients were treated during the study period (202 in stage II and 168 in stage III). Adjuvant chemotherapy was administered to 22 and 70% of patients in stage II and III respectively. The median follow-up period was 4.6 years. The 5-year survival rate for stage II patients was 79% and there was no benefit observed with adjuvant chemotherapy. For stage III patients, the 5-year survival rate was 81% for patients who received adjuvant chemotherapy, compared to 56% for those who did not receive chemotherapy (hazard ratio (HR): 0.29; 95% confidence interval (CI): 0.15-0.56). The benefit of chemotherapy was found to persist after adjustment for other prognostic variables (HR: 0.47; 95% CI: 0.23-0.94).Conclusions: Patients with colon cancer in stage III who received adjuvant chemotherapy had a better overall survival.

A Case of Advanced Gastric Cancer Presenting as Multiple Colonic Lymphoid Hyperplasia / 대한소화기학회지

Gastric cancer frequently disseminates to the liver, lung, and bone via hematogeneous, lymphatic, or peritoneal routes. However, gastric adenocarcinoma that metastasize to the colon and that shows typical linea platisca pattern on colonofiberscopy has rarely been reported. Recently, the authors experience a case of advanced gastric cancer with colonic metastases in a 55-year-old female patient. Multiple colonic lymphoid hyperplasias were detected on colonofiberscopy and biopsy revealed metastatic gastric cancer to the colonic wall. She was treated with mFOLFOX (5-FU, oxaliplatin, leucovorin) and has achieved stable disease status without disease progression. Herein, we report a rare case of signet ring-cell gastric cancer which metastasized to the colon in the form of multiple colonic lymphoid hyperplasias.

Technique of Framework Cemented on Prepared Abutments to Obtain Passive Fit at Fixed Complete Denture: A 2-Year Follow-Up Report

The passive fit of implant-supported dentures is fundamental to the rehabilitation success due the absence of the periodontal ligament in osseointegrated implants. Many techniques to obtain passive fit have been reported in the literature, some inaccessible for the clinicians and dental laboratories. This case report presents a technique to fabricate fixed complete dentures aiming at obtain passive fit with reduced time and cost, but without demerit for the aesthetics, function and longevity. A 40-year-old woman was referred for treatment presenting some teeth in the maxilla and an edentulous mandible, reporting eating problems related to instability and little retention of the mandibular complete denture. Treatment based on the reverse planning was performed to guide the rehabilitation with a complete mandibular fixed complete denture and maxillary occlusal plane adjustment. The framework of the fixed complete denture was manufactured luting a cast metal bar above the prepared titanium cylinder abutments using resin cement. The aim of this technique was to obtain a fixed complete denture with passive fit presenting positive esthetic and functional outcomes after 2 years of follow-up.

A adaptação passiva de próteses implantossuportadas é fundamental para o sucesso da reabilitação devido à inexistência de ligamento periodontal em implantes osseointegrados. Inúmeras técnicas de confecção da infraestrutura destas próteses tem sido relatadas na literatura, algumas inacessíveis para os clínicos e laboratórios de prótese. Este relato de caso apresenta uma técnica para confecção de próteses totais fixas visando obtenção de adaptação passiva com tempo e custo reduzido, porém sem demérito à estética, função e longevidade. Uma paciente de 40 anos se apresentou para tratamento apresentando alguns dentes na maxila e mandíbula edêntula, relatando dificuldades na mastigação relacionados a instabilidade e falta de retenção da prótese total inferior. Foi realizado um planejamento reverso para orientar a reabilitação com prótese total mandibular fixa e adequação do plano oclusal da maxila. A infraestrutura da prótese total fixa foi confeccionada pela cimentação de uma barra metálica em cilindros de titânio preparados com cimento resinoso. O objetivo desta técnica foi obter uma prótese total fixa com adaptação passiva apresentando resultados positivos em termos de estética e função após 2 anos de acompanhamento.

Qualidade de vida em mulheres no climatério atendidas na Atenção Primária / Quality of life of postmenopausal women attended at Primary Health Care / Calidad de vida de las mujeres en climaterio tratadas en la Atención Primaria

A vivência do climatério está cada vez mais presente, e demanda estratégias que melhorem a qualidade de vida das mulheres nesse período. A pesquisa objetivou avaliar a qualidade de vida de mulheres na fase do climatério, com ou sem uso da terapia de reposição hormonal (TRH). Estudo epidemiológico longitudinal, com amostra de 99 mulheres para cada grupo. Avaliaram-se as características sociodemográficas, clínicas e comportamentais. Foram aplicados à amostra a Menopause Rating Scale (MRS) e o Medical Outcomes Study 36-item Short-Form Health Survey (SF-36). Utilizaram-se os testes t de student, Qui-quadrado e Tukey. As usuárias de TRH apresentaram média etária de 50,76 ± 3,63 anos, e as não usuárias de 48,95 ± 6,27anos (p=0,01). Relataram maior frequência de sintomas climatéricos de intensidade leve a moderada. Os aspectos sociais apresentaram escore abaixo de 50 para os dois grupos. Houve diferenças entre os grupos em relação aos componentes do SF-36 e MRS para estado geral de saúde, capacidade funcional, menor capacidade, depressão, insônia e fenômenos vasomotores.

The experience of menopause is increasingly present, and demand strategies to improve the quality of life of women during this period. This research aimed to evaluate the quality of life for women in the climacteric phase, with or without the use of hormone replacement therapy (HRT). This is a longitudinal epidemiological study of a sample of 99 women per group. It was evaluated the sociodemographic, clinical and behavioral characteristics. It was used the Menopause Rating Scale (MRS) and the Medical Outcomes Study 36-item Short-Form Health Survey (SF-36). For data analysis, it was used the Student t test, chi-square and Tukey. HRT users had an average age of 50.76 ± 3.63 years, and nonusers of 48.95 ± 6,27anos (p = 0.01). It was identified a higher frequency of moderate climacteric symptoms of mild intensity. The social aspects evidenced scores below 50 for the two groups. There were differences between groups with respect to the components of the SF-36 and MRS to general health, functional capacity, lower capacity, depression, insomnia and vasomotor phenomena.

La experiencia de la menopausia es cada vez más presente, demandando estrategias para mejorar la calidad de vida de las mujeres durante este periodo. Esa investigación tuvo como objetivo evaluar la calidad de vida de las mujeres en la fase climatérica, con o sin el uso de la terapia de reemplazo hormonal (TRH). Trata-se dé un estudio epidemiológico longitudinal, con una muestra de 99 mujeres por grupo. Fueran evaluadas las características sociodemográficas, clínicas y de comportamiento. Fueran aplicados a la muestra el Menopause Rating Scale (MRS) e el Medical Outcomes Study 36-item Short-Form Health Survey (SF-36). Utilizaran-se los testes t de Student, Qui-quadrado e Tukey. Las usuarias de TRH tenían una edad media de 50,76 ± 3,63 años, y las no usuarias de 48,95 ± 6,27anos (p = 0,01). Fue reportada una mayor frecuencia de síntomas climatéricos intensidad leve o moderada. Los aspectos sociales tuvieran puntuaciones por debajo de 50 para los dos grupos. Hubo diferencias entre los grupos con respecto a los componentes del SF-36 y el MRS para la salud en general, la capacidad funcional, la capacidad más baja, la depresión, el insomnio y los fenómenos vasomotores.

Study on adherecce to capecitabine among patiens with colorectal cancer and meetastatic breast cancer / Estudo de aderência a capecitabina em pacientes com câncer colorretal e câncer de mama metastático

Context Capecitabine, an oral drug, is as effective as traditional chemotherapy drugs. Objectives To investigate the adhesion to treatment with oral capecitabine in breast and colorectal cancer, and to determine any correlation with changes in patient’s quality of life. Methods Patients with colorectal cancer or breast cancer using capecitabine were included. The patients were asked to bring any medication left at the time of scheduled visits. The QLQ-C30 questionnaire was applied at the first visit and 8-12 weeks after treatment. Results Thirty patients were evaluated. Adherence was 88.3% for metastatic colon cancer, 90.4% for non-metastatic colon cancer, 94.3% for rectal cancer and 96.2% for metastatic breast cancer. No strong correlation between adherence and European Organisation for Research and Treatment of Cancer QLQ-C30 functional or symptom scale rates had been found. There was no statistically significant correlation between compliance and the functional and symptom scales of the questionnaire before and after chemotherapy, with the exception of dyspnea. Conclusions Although no absolute adherence to oral capecitabine treatment had been observed, the level of adherence was good. Health professionals therefore need a greater focus in the monitoring the involvement of patients with oral treatment regimens. Patients with lesser degrees of dyspnea had greater compliance. .

Contexto A capecitabina, uma droga oral, é tão eficaz quanto as drogas quimioterápicas tradicionais. Objetivos Investigar a adesão ao tratamento oral com capecitabina para câncer de mama e colorretal e determinar qualquer correlação com as mudanças na qualidade de vida do paciente. Métodos Pacientes com câncer colorretal ou de mama em uso de capecitabina foram incluídos. A cada consulta os pacientes trouxeram a medicação restante. O questionário de qualidade de vida QLQ- C30 foi aplicado na primeira visita e 8-12 semanas após o tratamento. Resultados Trinta pacientes foram avaliados. A adesão foi de 88,3% para o câncer de cólon metastático, 90,4% para o de cólon não-metastático, 94,3% para o de reto e 96,2% para o de mama metastático. Com exceção da dispnéia, não houve forte correlação entre adesão e as taxas European Organisation for Research and Treatment of Cancer QLQ-C30 em relação a escala funcional ou de sintomas no início ou após quimioterapia. Conclusões O nível de adesão foi bom, embora não houvesse adesão absoluta ao tratamento com capecitabina oral. Os profissionais de saúde, portanto, precisam dar maior atenção a pacientes em regimes de tratamento oral. Os pacientes com menor grau de dispneia tiveram maior adesão. Neoplasias colorretais, terapia .

Risk factors associated to diabetes in Mexican population and phenotype of the individuals who will convert to diabetes / Factores de riesgo asociados con diabetes en la población mexicana y fenotipo de los individuos que desarrollarán diabetes

Objective. To describe risk factors associated to the incidence of type 2 diabetes (T2D) in Mexican population and to define phenotypic (clinical, anthropometric, metabolic) characteristics present in the individual who will convert to diabetes, regardless of time of onset. Materials and methods. The Mexico City Diabetes Study began in 1990, with 2 282 participants, and had three subsequent phases: 1994, 1998, and 2008. A systematic evaluation with an oral glucose tolerance test was performed in each phase. For diagnosis of T2D, American Diabetes Association criteria were used. Results. The population at risk was 1939 individuals. Subjects who were in the converter stage (initially non diabetic that eventually converted to T2D) had, at baseline, higher BMI (30 vs 27), systolic blood pressure (119 vs 116 mmHg), fasting glucose (90 vs 82mg/dl), triglycerides (239 vs 196mg/dl), and cholesterol (192 vs 190mg/dl), compared with subjects who remained non converters (p<0.05). Conclusion. The phenotype described represents a potentially identifiable phase and a target for preventive intervention.

Objetivo. Describir los factores de riesgo asociados con la incidencia de diabetes tipo 2 (T2D) en la población mexicana, así como el fenotipo de los sujetos que desarrollarán diabetes, independientemente del tiempo que lleve el desarrollo de esta nueva condición. Material y métodos. El Estudio de la Diabetes de la Ciudad de México inició en 1990 y tuvo un total de 2 282 participantes a los que se dio seguimiento en tres ocasiones: 1994, 1998 y 2008. Se realizó una curva de tolerancia a la glucosa para diagnosticar T2D, para lo cual se siguieron los criterios de la Asociación Americana de Diabetes. Resultados. La población en riesgo fue de 1939 sujetos. Los individuos en proceso de desarrollo (aquellos inicialmente no diabéticos que desarrollaron T2D) mostraron niveles más altos de IMC (30 vs 27), presión arterial sistólica (119 vs 116 mmHg), glucosa en ayuno (90 vs 82 mg/dl), triglicéridos (239 vs 196 mg/dl) y colesterol (192 vs 190 mg/dl), comparados con los sujetos que no desarrollaron T2D (p<0.05). Conclusiones. El estado de los individuos que se convertirán en diabéticos es discernible y representa una fase del padecimiento con potencial para la prevención.

Role of neoadjuvant concurrent chemoradiation in locally advanced unresectable pancreatic cancer: A feasibility study at tertiary care centre.

BACKGROUND: Pancreatic cancer has an extremely poor prognosis and prolonged survival is achieved only by resection with macroscopic tumor clearance. There is a strong rationale for a neoadjuvant approach, since a relevant percentage of pancreatic cancer patients present with non‑metastatic but locally advanced disease. The objective of the present study was to assess the effect of neoadjuvant chemoradiation therapy (NACRT) on tumor response, down staging and resection, toxicity and any survival advantage. MATERIALS AND METHODS: A prospective pilot study was carried out from January 2009 to June 2011 in which 15 patients of locally advanced unresectable pancreatic cancer were included. All patients were treated with NACRT protocol with oral Capecitabine and 3D conformal radiotherapy (3DCRT) of 30 Gy in 10 fractions. The patients were restaged 3 to 4 weeks after the completion of NACRT and explored for resection. RESULTS: Out of 15 patients, fourteen were evaluable. Four patients underwent surgery, 5 had partial response but remained unresectable, 2 patients had stable disease and 3 had progressive disease. Most of the toxicities were slight and were in grade 1 to 2. None of the patients developed grade 3 or 4 gastrointestinal or hematological toxicity. The median survival was 15 months for resected patients and 8.6 months for unresected patients, respectively. The 2 year actuarial overall survival was 34.6%. CONCLUSION: All patients with locally unresectable pancreatic cancer should be offered chemoradiation therapy, in hopes of down staging the tumor for possible resection and achieving higher survival.

Radioquimioterapia adyuvante en cáncer gástrico completamente resecado: experiencia del Instituto Nacional del Cáncer de Chile / Adjuvant chemoradiotherapy in advanced gastric cancer: Experience in 168 patients

Background: Gastric cancer is one of the most lethal tumors in the Chilean population. Aim: To report the results of adjuvant chemoradiotherapy in advanced gastric cancer. Material and Methods: Review of medical records of patients with locoregionally advanced gastric cancer, subjected to a curative resection and treated with adjuvant chemoradiotherapy. The treatment was based on the INT 0116/SWOG protocol, which includes 5-fuorouracil as a single agent. Patients were followed for a median of 58 months. Results: the records of 168 patients (99 men) treated between 2004 and 2011, were reviewed. Median survival was 41 months. Median lapses between surgery and onset of chemo and radiotherapy were 12 and 17 weeks, respectively. Overall three and five years survival was 53 and 41%, respectively. On multivariate analysis the factors associated with a lower survival were an antral location of the tumor, presence of signet ring cells and more than 15 involved lymph nodes. Conclusions: Three and five years survival of gastric cancer patients subjected to adjuvant chemoradiotherapy was 53 and 41% respectively. These results are similar to those reported elsewhere.