Clinical Anslysis of Primary Adrenal NK/T-Cell Lymphoma / 中国实验血液学杂志

OBJECTIVE@#To investigate the clinical characteristics, diagnosis, and treatment of one patient with primary adrenal natural killer/T-cell lymphoma (PANKTCL), and to strengthen the understanding of this rare type of lymphoma.@*METHODS@#The clinical manifestations, diagnosis and treatment process, and prognosis of the patient admitted in our hospital were retrospectively analyzed.@*RESULTS@#Combined with pathology, imaging, bone marrow examination， etc, the patient was diagnosed with PANKTCL (CA stage, stage II; PINK-E score 3, high-risk group). Six cycles of "P-GemOx+VP-16" regimen（gemcitabine 1 g/m2 d1 + oxaliplatin 100 mg/m2 d 1 + etoposide 60 mg/m2 d 2-4 + polyethylene glycol conjugated asparaginase 3 750 IU d 5） was performed, and complete response was assessed in 4 cycles. Maintenance therapy with sintilimab was administered after the completion of chemotherapy. Eight months after the complete response, the patient experienced disease recurrence and underwent a total of four courses of chemotherapy, during which hemophagocytic syndrome occurred. The patient died of disease progression 1 month later.@*CONCLUSION@#PANKTCL is rare, relapses easily, and has a worse prognosis. The choice of the "P-GemOx+VP-16" regimen combined with sintilimab help to improve the survival prognosis of patient with non-upper aerodigestive tract natural killer /T-cell lymphoma.

Caracterización clínico-epidemiológica de la urolitiasis / Clinical-epidemiological description of urolithiasis

Introducción: Las urolitiasis ocasionan dolor, deterioro funcional renal y notorias erogaciones económicas. Objetivos: Identificar las características clínico-epidemiológicas de la nefrolitiasis. Métodos: Estudio descriptivo, transversal. Se estudiaron 2 923 personas pertenecientes a tres consultorios del Policlínico Plaza; municipio Plaza de la Revolución, provincia La Habana, Cuba., seleccionados por muestreo simple aleatorio de los 16 con que cuenta el área de salud. Los datos se obtuvieron mediante encuesta y entrevista estructurada. La información fue procesada de forma automatizada (IBMSPSS 22.0). Se utilizó análisis de distribución de frecuencias, se calcularon tasas de prevalencia, y fue empleado el test de homogeneidad. Resultados: La prevalencia de urolitiasis fue de 4,99 por cada 100 habitantes, de 6,3 entre los varones y de 5,7 en los de piel blanca. La edad promedio al diagnóstico fue de 39,3 años. Entre los factores de riesgo de litiasis predominó la alta ingestión de oxalatos (97,3 por ciento). La ecografía fue la forma de diagnóstico más usada (67,8 por ciento). La fitoterapia fue el tratamiento médico más utilizado (69,2 por ciento). Al 16,4 por ciento de los pacientes se les expidió certificado médico en los últimos dos años. Conclusiones: La prevalencia de litiasis urinaria en el Policlínico Docente Plaza de la Revolución es elevada, con predominio en el sexo masculino, en sujetos de piel blanca y en las edades medias de la vida. La alta ingestión de oxalato es el factor de riesgo de litiasis urinaria más frecuente encontrado. La forma de diagnóstico más utilizada es la ecografía y el tratamiento más empleado es la fitoterapia(AU)

Introduction: Urolithiasis causes pain, renal functional deterioration and notorious economic expenses. Objectives: To identify the clinical-epidemiological characteristics of nephrolithiasis. Methods: A descriptive, cross-sectional study was conducted in a total of 2,923 people from to three clinics of Plaza de la Revolution Teaching Community Clinic, Plaza de la Revolution municipality, Havana province, Cuba. They were selected by simple random sampling from the 16 clinics that the health area has. The data was obtained through a survey and structured interview. The information was processed automatically (IBMSPSS 22.0). Frequency distribution analysis was used, prevalence rates were calculated and the homogeneity test was used. Results: The prevalence of urolithiasis was 4.99 per 100 inhabitants, 6.3 among men and 5.7 among white-skinned men. The average age at diagnosis was 39.3 years. Among the risk factors for lithiasis, the high intake of oxalates prevailed (97.3 percent). Ultrasound was the most used form of diagnosis (67.8 percent). Phytotherapy was the most used medical treatment (69.2 percent). A medical permit was issued to 16.4 percent of the patients in the last two years. Conclusions: The prevalence of urinary lithiasis in Plaza de la Revolution Teaching Community Clinic is high, prevailing in males, in white-skinned and middle aged subjects. High oxalate intake is the most common risk factor for urinary lithiasis found. The most used form of diagnosis is ultrasound and the most used treatment is phytotherapy(AU)

Índice pronóstico nutricional en pacientes con cáncer de páncreas avanzado tratados con nimotuzumab combinado a quimioterapia / Nutritional prognostic index in patients with advanced pancreatic cancer treated with nimotuzumab combined with chemotherapy

Introducción: El índice pronóstico nutricional es un marcador inmuno-nutricional que puede ser útil como factor pronóstico en tumores gastrointestinales. Objetivo: Evaluar supervivencia de pacientes con adenocarcinoma pancreático avanzado tratados con quimioinmunoterapia según índice pronóstico nutricional, según parámetros clínico-patológicos y tratamiento. Métodos: Se realizó estudio retrospectivo y observacional en pacientes que recibieron quimioterapia gemcitabina-oxaliplatino combinado a nimotuzumab (n=118), en el Hospital Ameijeiras, entre 2014 y 2019. Se evaluó supervivencia por método Kaplan-Meier, y regresión de Cox, para determinar los factores pronósticos independientes de supervivencia. Resultados: El punto de corte seleccionado fue 40 (sensibilidad 52,9 por ciento y especificidad 85,7 por ciento (p = 0,019), con área bajo la curva de 0,693. Para pacientes con índice menor de 40, la supervivencia fue más baja respecto a los pacientes con índice ≥ 40 (11,4 meses frente a 16,0 meses; p=0,001), con un HR de 1,7 (1,13-2,60; p=0,011). Las variables mayormente asociadas con índice pronóstico nutricional altos son pacientes con sesenta años o menos; ECOG cero, índice de masa corporal ≥25 Kg/m2 y albúmina sérica >3,5g/dL (x² < 0,05). Los pacientes con índice ≥ 40 tienen medianas de supervivencia más altas que pacientes con índice < 40 en las variables seleccionadas con p < 0,05, excepto el índice de masa corporal. Conclusiones: Este trabajo constituye el primer reporte nacional de utilización del índice pronóstico nutricional como pronóstico de supervivencia en pacientes con cáncer de páncreas avanzado(AU)

Background: The nutritional prognostic index is an immuno-nutritional marker that can be useful as a prognostic factor in gastrointestinal tumors. Aim: To evaluate the survival of patients with advanced pancreatic adenocarcinoma treated with chemoimmunotherapy according to the nutritional prognostic index, according to clinical-pathological parameters and treatment. Methods: A retrospective and observational study was carried out in patients who received gemcitabine-oxaliplatin chemotherapy combined with nimotuzumab (n=118), at the Ameijeiras Hospital, between 2014 and 2019. Survival was evaluated by the Kaplan-Meier method, and Cox regression, for determine independent prognostic factors for survival. Results: The selected cut-off point was 40 (52.9 percent sensitivity and 85.7 percent specificity) (p=0,019), with an area under the curve of 0,693. For patients with an index less than 40, survival was lower compared to patients with index ≥ 40 (11, 4 months vs. 16, 0 months; p=0,001), with a HR of 1, 7 (1, 13-2, 60; p=0,011). The variables mostly associated with nutritional prognostic index patients with 60 years or less, ECOG 0, body mass index ≥ 25 kg/m2 and serum albumin >3,5g/dL (x2 < 0, 05). Patients with index ≥ 40 have higher median survival than patients with index < 40 in the selected variables with p < 0, 05, except body mass index. Conclusions: This work constitutes the first national report on the use of the nutritional prognostic index as a prognosis of survival in patients with advanced pancreatic cancer(AU)

Foot drop - an uncommon presentation of FOLFOX toxicity

A quimioterapia com FOLFOX (oxaliplatina, leucovorina e 5-fluorouracilo) é frequentemente utilizada em doentes com cancro colorretal. Os sais de platina são conhecidos por serem uma classe de quimioterápicos que comumente induzem neurotoxicidade periférica. Na toxicidade induzida pela oxaliplatina, os sintomas sensitivos são os mais frequentes. Neste artigo, apresentamos dois casos clínicos de pacientes com adenocarcinoma de cólon, ambos submetidos à quimioterapia com FOLFOX4, e que desenvolveram neurotoxicidade incomum, apresentando pé pendente após o terceiro ciclo de tratamento. Esta manifestação clínica pode ser explicada por dano axonal nos neurônios motores periféricos do nervo peroneal comum (fibular), que fornece inervação motora aos músculos do pé. A paralisia do nervo fibular causa fraqueza súbita nos músculos do pé, que parece ser temporária. Ambos os doentes recuperaram completamente do evento sem necessidade de ajustes no tratamento, nem introdução de medicamentos diferentes. A apresentação de pé pendente como toxicidade da quimioterapia ainda é pouco compreendida. Os casos relatados mostram o pé pendente como uma manifestação grave e incomum de neuropatia induzida por FOLFOX, que pode ser transitória, e não requer necessariamente intervenção específica.

Chemotherapy based on FOLFOX (oxaliplatin, leucovorin, and 5-fluorouracil) regimen is frequently used in colorectal cancer patients. Oxaliplatin and other platinum agents are known to be a class of chemotherapy drugs that commonly induce peripheral neurotoxicity. The most frequent oxaliplatin related neurotoxicity is sensitive symptoms. Here, we present two cases of patients with colon adenocarcinoma, both undergoing chemotherapy with FOLFOX4, who developed uncommon neurotoxicity, presenting with foot drop after the third treatment cycle. Foot drop may be explained by axonal damage of peripheral motor neurons of the common peroneal (fibular) nerve, which provides motor innervation to the foot muscles. Peroneal nerve palsy causes sudden weakness in the muscles of the foot that seems to be temporary. Both patients completely recovered from the event. There was no need for treatment adjustments, neither introduction of different drugs. Foot drop as chemotherapy toxicity is still poorly understood. The reported cases show foot drop as a severe and uncommon manifestation of FOLFOX-induced neuropathy, that might be transitory, and does not necessarily requires specific intervention.

Hepatectomía en dos tiempos por metástasis hepáticas bilobares de origen colorrectal: reporte de un caso / Two-stage hepatectomy for bilobar colorectal liver metastases: case report / Hepatectomia em dois estágios para metástases hepáticas bilobares de origem colorretal: relato de um caso

La mitad de los pacientes con cáncer de origen colorrectal desarrollan metástasis hepáticas durante el curso de su enfermedad y de esas el 80% son irresecables. La resecabilidad se define no por la extensión de la hepatectomía, sino por la función del hígado remanente, por lo que para pacientes con ciertos factores favorables se pueden realizar técnicas de remodelación hepática para aumentar el volumen del hígado remanente para que este sea suficiente. La hepatectomía en dos tiempos se basa en procedimientos secuenciales que buscan tratar metástasis hepáticas colorrectales consideradas inicialmente irresecables, logrando la resección completa de las mismas dejando un remanente hepático funcionante suficiente, lo cual no sería posible en un solo acto quirúrgico. El objetivo de este trabajo es presentar el caso clínico de un paciente portador de metástasis hepáticas sincrónicas de origen colorrectal irresecables, que luego de una quimioterapia de conversión, con el fin de aumentar el futuro remanente hepático y evitar falla hepática postoperatoria y realizar una resección oncológica, fue sometido a una hepatectomía en dos tiempos, técnica utilizada con baja frecuencia en nuestro medio, destacando una evolución favorable, con marcadores tumorales en valores normales y sin evidencia imagenológica de recaída local ni sistémica.

Half of colorectal cancer patients develop liver metastases during the course of their disease, 80% of which are unresectable. Resectability is defined not by the extent of the hepatectomy, but by the function of the liver remnant. Therefore, for patients with certain factors, liver remodeling techniques can be performed to increase volume of the remaining liver so that it is sufficient. Two-stage hepatectomy is performed on colorectal liver metastases which are initially considered unresectable in one stage resection procedures, in which sequential procedures are performed in order to achieve complete resection and preserve a sufficient functioning liver remnant. The objective of this paper is to present the case of a patient with unresectable synchronous colorectal liver metastases, in which after conversion chemotherapy, in order to increase the future liver remnant, avoid postoperative liver failure and perform an oncological resection underwent a two-stage hepatectomy, a technique used with low frequency in our setting, highlighting a favorable evolution, with tumor markers in normal values and without imaging evidence of local or systemic relapse.

Metade dos pacientes com câncer colorretal desenvolve metástases hepáticas durante o curso da doença e, desses, 80% são irressecáveis. A ressecabilidade é definida não pela extensão da hepatectomia, mas pela função do fígado remanescente; portanto, para pacientes com certos fatores favoráveis, técnicas de remodelação hepática podem ser realizadas para aumentar o volume do fígado remanescente de forma que seja suficiente. A hepatectomia em dois estágios é baseada em procedimentos sequenciais que buscam tratar metástases hepáticas colorretais inicialmente consideradas irressecáveis, obtendo ressecção completa, deixando um remanescente hepático funcional suficiente, o que não seria possível em um único ato cirúrgico. O objetivo deste trabalho é apresentar o caso clínico de um paciente com metástases hepáticas sincrônicas irressecáveis ​​de origem colorretal, que após quimioterapia de conversão, com o objetivo de aumentar o futuro remanescente hepático e evitar insuficiência hepática pós-operatória e realizar uma ressecção oncológica, foi submetido a dois Hepatectomia em estágio, técnica utilizada com baixa frequência em nosso meio, evidenciando evolução favorável, com marcadores tumorais em valores normais e sem evidências de imagem de recidiva local ou sistêmica.

Protocolo de desensibilización rápida en pacientes con reacción moderada a severa de hipersensibilidad a citostáticos / Rapid desensitization protocol in patients with moderate to severe hypersensitivity reaction to cytostatics

Introducción: La desensibilización rápida a medicamentos induce una tolerancia temporal a los quimioterapéuticos que provocan reacciones de hipersensibilidad. Objetivo: Evaluar el protocolo de desensibilización rápida en escenario ambulatorio en pacientes que presentaron reacciones de hipersensibilidad a fármacos citotóxicos. Métodos: Se realizó un estudio observacional, y retrospectivo, de 30 pacientes con cáncer que desarrollaron reacciones de hipersensibilidad entre los años 2016 y 2018, tratados en el Hospital de Día del Servicio de Oncología del Clínico Quirúrgico Hermanos Ameijeiras. Se clasificaron según su intensidad, y se analizaron variables demográficas, características clínicas, y síntomas presentados. Se utilizó un protocolo en doce etapas basado en tres diluciones del fármaco. Se administró premedicación en todos los casos. Se realizó estadística descriptiva, y para la asociación entre variables, se utilizó la prueba estadística Chi-cuadrado. Resultados: La mediana de edad fue 54 años (23;77). Predominaron las mujeres; los menores de 60 años; tumor primario de colon; antecedentes de alergia; el oxaliplatino como fármaco más implicado; las RHS durante la infusión; e intensidad moderada. Fueron más frecuentes los síntomas cutáneos y gastrointestinales. Con la aplicación del protocolo se completó la quimioterapia planificada a los 30 pacientes (145 ciclos adicionales). Solo se presentaron ocho desensibilizaciones con reacciones leves de tipo cutáneas. El 94,5 por ciento de las desensibilizaciones no presentaron reacción alguna. Conclusiones: Constituye el primer reporte nacional de la utilización exitosa de un protocolo de desensibilización rápida a citostáticos que demostró ser eficaz y seguro en el escenario ambulatorio, con un manejo multidisciplinario(AU)

Introduction: Rapid desensitization to drugs induces a temporary tolerance to chemotherapeutics causing hypersensitivity reactions. Objective: To evaluate the rapid desensitization protocol in an outpatient setting in patients who had hypersensitivity reactions to cytotoxic drugs. Methods: An observational and retrospective study was carried out in 30 cancer patients, who developed hypersensitivity reactions, from 2016 to 2018. They were treated in the outpatient Oncology service at Hermanos Ameijeiras Surgical Clinical Hospital. These subjects were classified according to intensity; demographic variables, clinical characteristics, and symptoms were analyzed. A twelve-step protocol based on three dilutions of the drug was used. Premedication was administered in all cases. Descriptive statistics and for the association between variables were performed. Chi-square statistical test was used. Results: The median age was 54 years (23; 77). Predominance was observed in women, those under 60 years of age, primary colon tumor, history of allergy, oxaliplatin as the drug most implicated, HRH during infusion, and moderate intensity. Skin and gastrointestinal symptoms were more frequent. The planned chemotherapy was completed with the application of the protocol, in all 30 patients (145 additional cycles). There were only eight desensitization with mild skin-type reactions. 94.5 percent of desensitizations did not show any reaction. Conclusions: It constitutes the first national report of successful use of a rapid desensitization protocol to cytostatics that proved to be effective and safe in the outpatient setting with multidisciplinary management(AU)

Adjuvant chemotherapy in locally advanced rectal cancer: deciding on the optimal strategy

ABSTRACT Background: Neoadjuvant therapy, followed by surgery, reduces the risk of local relapse in rectal cancer, but approximately 30% will relapse with distant metastases, highlighting the importance of adjuvant chemotherapy (aCT). Objective: The objective of the study was to study two regimens of adjuvant treatment in patients with locally advanced rectal cancer and analyze their efficacy and toxicity. Methods: Between January 2009 and December 2016, 193 patients with Stage II-III rectal cancer who had received neoadjuvant therapy were included by consecutive non-probability sampling. The decision to administer aCT, as well as the specific regimen, was at the discretion of the medical oncologist. Disease-free survival (DFS) and overall survival (OS) were calculated. Results: The mean DFS was 84.85 (95% confidence interval [CI]: 79-90) months in 164 patients receiving aCT, compared to 57.71 (95% CI: 40-74) months in 29 who did not receive aCT (p < 0.001). Then, mean OS was 92.7 (95% CI: 88-97) months and 66.18 (95% CI 51-81) months, respectively (p < 0.001). DFS was 83.6 (95% CI: 76-91) months in 74 patients receiving adjuvant 5-fluorouracil (5-FU), and 82.9 (95% CI: 75-90) months in 90 receiving 5-FU plus oxaliplatin (p = 0.49). OS was 87 (95% CI: 80-94) versus 93.65 (95% CI: 88-99) months, respectively (p = 0.76). The multivariate analysis identified aCT hazard ratio (HR) 0.30 (95% CI: 0.1-0.46), perineural invasion HR 3.36 (95% CI: 1.7-6.5), and pathological complete response HR 0.10 (95% CI; 0.01-0.75) as independent markers of DFS. Conclusions: In our study, aCT was associated with longer DFS and OS. 5-FU plus oxaliplatin showed greater toxicity with no added benefit in DFS or OS.

Evolução Clínica e Preditores da Neuropatia Periférica Induzida por Quimioterapia / Clinical Evolution and Predictors of Chemotherapy-Induced Peripheral Neuropathy / Evolución Clínica y Predictores de la Neuropatía Periférica Inducida por Quimioterapia

Introdução: Drogas antineoplásicas neurotóxicas estão frequentemente associadas à neuropatia periférica induzida por quimioterapia (NPIQ). Objetivo: Avaliar a evolução clínica dos pacientes expostos a tratamento antineoplásico potencialmente neurotóxico e identificar possíveis preditores clínicos e sociodemográficos para o desenvolvimento da NPIQ. Método: Estudo de coorte prospectiva com pacientes com diagnóstico de câncer de mama, ovário ou intestino em tratamento quimioterápico com paclitaxel, docetaxel ou oxaliplatina. Foram avaliados antes da quimioterapia (T1), no terceiro mês (T2) e 30-60 dias após interrupção do tratamento (T3). Todos responderam ao questionário de perfis sociodemográfico e clínico, foram avaliados por meio de exame clínico neurológico, pela escala de performance ECOG, escala hospitalar de ansiedade e depressão (HAD), escala de dor Short-cGuill, autorrelato de sintomas de NPIQ e avaliação com o questionário de neurotoxicidade induzida por antineoplásicos (CINQ). Resultados: Por meio de autorrelato, 75% da dos pacientes informaram apresentar sintomas de NPIQ. O CINQ evidenciou que 90% apresentaram algum grau de NPIQ em T2, enquanto 82,5% ainda persistiam em T3. Dor neuropática acometeu 42% da população (RR=1,429; IC95%=1,130-1,806). Os escores de ansiedade e depressão reduziram significativamente quando comparados ao início de tratamento (redução de 2,5 pontos na escala HAD, p<0,05). A capacidade funcional da população não mostrou alterações significativas. No T2, a escolaridade foi considerada preditora para autorrelato de sintomas de NPIQ (OR=1,314, IC95%=1,002-1,723, p=0,048). Conclusão:A baixa escolaridade pode comprometer a capacidade do paciente em relatar os sintomas da NPIQ. Este estudo chama a atenção para a necessidade de utilização de instrumentos específicos para detecção precoce da NPIQ.

Introduction: Neurotoxic antineoplastic drugs are frequently associated to chemotherapy-induced peripheral neuropathy (CIPN). Objective: To evaluate the clinical evolution of patients exposed to potentially neurotoxic antineoplastic treatment and to identify possible clinical and sociodemographic predictors for the development of CIPN. Method: Cohort prospective study with patients with breast, ovary or intestine diagnosis of cancer in chemotherapy treatment with paclitaxel, docetaxel or oxaliplatin. They were assessed before the chemotherapy (T1), in the third month (T2) and 30-60 days after the interruption of the treatment (T3). All the patients responded to the questionnaire of clinical and sociodemographic profiles, were evaluated through neurologic clinical exam, by the performance scale ECOG, by the Hospital Anxiety and Depression Scale - HAD, pain scale of Short-cGuill, self-report of symptoms of CIPN and evaluation with the questionnaire of antineoplastic-induced neurotoxicity (QAIN). Results: Through self-report, 75% of the patients presented symptoms of CIPN. The QAIN showed that 90% presented a certain degree of CIPN in T2, while 82.5% still persisted in T3. Neuropathic pain affected 42% of the population (RR = 1.429, CI95% = 1.130-1.806). Anxiety and depression scores significantly reduced when compared with the beginning of the treatment (reduction of 2.5 points in the scale HAD, p < 0.05). The functional capacity of the population did not show any significant change. The school level was considered a predictor of self-report of CIPN symptoms in T2 (OR = 1.314, CI95% = 1.002-1.723, p = 0.048). Conclusion: The low school level may taint the patient capacity to report CIPN symptoms. This study draws attention for the necessity to use specific instruments for early detection of CIPN.

Introducción: Los fármacos antineoplásicos neurotóxicos a menudo se asocian con neuropatía periférica inducida por quimioterapia (CIPN). Objetivo: Evaluar la evolución clínica de pacientes expuestos a tratamientos antineoplásicos potencialmente neurotóxicos e identificar posibles predictores clínicos y sociodemográficos para el desarrollo de CIPN. Método: Estudio de cohorte prospectivo con pacientes diagnosticadas con cáncer de mama, ovario o intestino sometidos a quimioterapia con paclitaxel, docetaxel u oxaliplatino. Se evaluaron antes de la quimioterapia (T1), en el tercer mes (T2) y 30-60 días después de la interrupción del tratamiento (T3). Todos respondieron el cuestionario de perfil sociodemográfico y clínico, se evaluaron mediante un examen neurológico clínico, la escala de rendimiento ECOG, la escala de ansiedad y depresión hospitalaria (HAD), la escala de dolor Short-cGuill, el autoinforme de los síntomas de CIPN y la evaluación con el cuestionario de neurotoxicidad inducida por antineoplásicos (CINQ). Resultados: Por autoinforme, el 75% de la población informó presentar síntomas de CIPN. El CINQ mostró que el 90% tenía algún grado de NPIQ en T2, mientras que el 82.5% aún persistía en T3. El dolor neuropático afectó al 42% de la población (RR = 1.429; IC del 95% = 1.130-1.806). Las puntuaciones de ansiedad y depresión disminuyeron significativamente en comparación con el valor inicial (reducción de 2.5 puntos HAD, p <0.05). La capacidad funcional de la población no mostró cambios significativos. En T2, la educación se consideró un predictor de síntomas CIPN autoinformados (OR=1.314, IC 95%=1.002-1.723, p=0,048). Conclusión: La baja educación puede comprometer la capacidad del paciente para informar los síntomas de CIPN. Este estudio llama la atención sobre la necesidad de utilizar instrumentos específicos para la detección temprana de CIPN.

Relationship between the Asp1104His polymorphism of the nucleotide excision repair gene ERCC5 and treatment sensitivity to oxaliplatin in patients with advanced colorectal cancer in China

OBJECTIVES: To study the relationship between the Asp1104His polymorphism of the nucleotide excision repair gene ERCC5 and treatment sensitivity to oxaliplatin in patients with advanced colorectal cancer (CRC) in China. METHODS: A group of 226 patients in the Department of Gastrointestinal Oncology at Zhejiang Xiaoshan Hospital from July 2011∼December 2016 and a control group of 226 normal healthy individuals were involved in this study. All patients were first diagnosed with advanced CRC and were treated with oxaliplatin-based chemotherapy. The genotype of ERCC5 at the site of amino acid 1104 was determined by a TaqMan probe-based real-time PCR approach. RESULTS: There were no differences in age or gender between the groups, but the percentages of smokers and individuals with a family history of cancer were significantly higher in the patient group than in the control group. Analysis of the G/C polymorphism frequency among the patients and the healthy controls showed that the frequencies of the CC genotype and the CC+GC genotype were significantly related to CRC, but no significant difference in these frequencies was found between genders. The analysis of the relationship between the 5-year survival rate and different genotypes showed that in the total patient group, regardless of gender, the 5-year survival rate was significantly associated with the Asp1104His polymorphism of ERCC5. CONCLUSIONS: The Asp1104His polymorphism of ERCC5 was associated with the risk and 5-year survival rate of CRC as well as treatment sensitivity to oxaliplatin.

Desarrollo tecnológico y estudio de estabilidad de una formulación de oxaliplatino 100 mg, solución inyectable / Technological development and stability study of a 100 mg oxaliplatinum formulation in injectable solution

Introducción: el oxaliplatino, es un análogo de los complejos derivados del platino en el cual el átomo de platino central está rodeado por un oxalato y en posición trans el 1,2‒diaminociclohexano. La cinética de enlace del oxaliplatino sobre el ADN se produce en 15 minutos como máximo y en comparación con el cisplatino presenta una cinética bifásica de 4 a 8 horas y demuestra mayor eficacia sobre ciertos tumores. Objetivo: diseñar una formulación de oxaliplatino, solución inyectable, conteniendo 100 mg del ingrediente activo por bulbo, que cumpla con los índices de calidad para esta forma farmacéutica y proporcione el efecto terapéutico deseado. Métodos: se realizaron los estudios de formulación correspondientes y se ensayaron cinco variantes tecnológicas, en las que se ajustó el pH de la formulación según las exigencias de un preparado parenteral. Se efectuó un estudio de temperatura, para lograr la disolución del principio activo, sin que se afectaran sus propiedades, dada su poca solubilidad en medio acuoso. Se estudiaron diferentes materiales de envase y temperaturas de conservación del producto, además se estandarizó una técnica analítica por Cromatografía Líquida de Alta Resolución para la estabilidad de la formulación, determinar su fecha de vencimiento y para su control de la calidad. Resultados: el desarrollo tecnológico resultó satisfactorio, en una de las variantes ensayadas, se obtuvo un producto que cumple con todas las especificaciones descritas en la monografía para el control de la calidad del preparad, mantiene sus propiedades físicas, químicas y microbiológicas inalterables por un período de 18 meses, almacenada a temperatura ambiente, con un escalado a nivel piloto, sin que se presentaran problemas tecnológicos. Conclusiones: se obtuvo la formulación de un medicamento en forma de solución inyectable, que contiene oxaliplatino como principio activo, que cumple con todas las especificaciones de calidad para este tipo de forma farmacéutica, lo que aumenta arsenal terapéutico de Cuba(AU)

Introduction: oxaliplatinum is an analogue of the platinum-derived complexes in which the central platinum atom is surrounded by an oxalate and 1,2?diaminocyclohexane in transposition. The link kinetics of oxaliplatinum on the DNA occurs in 15 minutes at most and if compared with the cysplatinum, it presents a 4-8 h biphasic kinetics and higher efficacy over certain tumors. Objective: to design an oxaliplatinum formulation, for injection solution that contains 100mg of the active ingredient per ampoule, comply with the quality parameters for this pharmaceutical form and provides the desired therapeutic effect. Methods: the corresponding formulation studies were performed together with the testing of five technological variants in which the formulation pH was adjusted according to the requirements of a parenteral product. A temperature study was also conducted to reach dissolving the active principle without any damage to its properties, given that it is poorly water-soluble. Different packing materials and storage temperatures of the product were studied in addition to standardizing an analytical technique based on high performance liquid chromatography for the stability of the formulation, estimation of the expiry date and for the quality control. Results: the technological development was satisfactory in one of the tested variants. The obtained product complied with all the described specifications in the monograph for the quality control of the product; its physical, chemical and microbiological properties remained unchanged for a period of 18 months and stored at room temperature, with pilot scale-up with no further technological problems. Conclusions: there was obtained the formulation of a drug in its injectable form that contains oxaliplatinum as active ingredient, complies with all the quality specifications for this pharmaceutical form and increases the therapeutical arsenal available in Cuba(AU)