La genética de la epilepsia en la práctica clínica / The genetics of epilepsy in the clinical practice

Resumen La epilepsia es un trastorno neurológico caracterizado por crisis epilépticas recurrentes no provocadas, en el cual la genética tiene un factor etiológico importante. Durante las últimas décadas se ha logrado encontrar genes específicos involucrados en la patogénesis de esta condición. Actualmente existen múltiples exámenes disponibles en la práctica clínica para el diagnóstico genético, siendo los más útiles los paneles multi-genes y la secuenciación del exoma completo por medio de next generation sequencing (NGS). El tener un diagnósti co genético puede mejorar la calidad de vida de cada paciente y su familia, al mismo tiempo que nos ayuda a individualizar el tratamiento haciéndolo más eficaz. Algunos ejemplos en los que el diagnóstico genético puede modificar la conducta terapéutica incluyen el gen SCN1A en que se recomienda no utilizar medicamentos bloqueadores de canales de sodio y el gen SLC2A1 en el que se recomienda el inicio de la dieta cetogénica. El futuro de la investigación en medicina de precisión en epilepsia es muy prometedor, con el objetivo de que cada paciente reciba un tratamiento acorde a su etio logía genética.

Abstract Epilepsy is a neurological disorder characterized by recurrent unprovoked seizures. It is known that genetics play an important etiology roll. During the last decades it has been possible to find specific genes involved in the pathogenesis of this condition. There are currently multiple studies available in clinical practice for genetic diagnosis, the most useful being the next generation se quencing (NGS) techniques with multi-gene panels and whole exome sequencing. Having a genetic diagnosis can help improve the quality of life of each patient and their family, while it helps us to individualize the treatment, making it more effective. Some examples in which ge netic diagnosis can modify therapeutic conduct include the SCN1A gene, in which it is recommended not to use drugs that block Sodium channels, and the SLC2A1 gene, in which starting ketogenic diet is recommended. The future of precision medicine research in epilepsy is very promising, with the goal that each patient receives treatment according to their genetic etiology.

Perception of the healthcare accreditation system in Colombia / Percepción del sistema de acreditación sanitaria en Colombia

Abstract Introduction: Accreditation is an external, systematic, periodic, and voluntary evaluation process to which health care institutions submit themselves in order to demonstrate compliance with superior levels of quality of care. The Icontec, through an evaluative model, accredits the quality of health institutions in Colombia. Methods: Descriptive cross-sectional study following the recommendations of the survey study report. Using an electronic format, 22 health institutions with experience in the Icontec accreditation process were surveyed. The instrument evaluated three thematic axes of the process: added value provided by the accreditation process, evaluation process and final report. The measurement was carried out using a Likert-type scale and a descriptive statistical analysis to establish the perception of the phases of the process. Results: the items with the best perception were the humanization of care (86.4%) followed by patient safety and teamwork (81.8%). After accreditation, the quality of the processes improved (77.4%), infection prevention and control (68.1%) and physician commitment (63.6%). 54.6% felt that evaluators use different methods of evaluation. 63.6% of the respondents considered that Icontec does not comply with the times defined for the delivery of the report. Conclusion: the Icontec accreditation system adds value to health institutions in most of the thematic areas evaluated, especially in the humanization of care and patient safety. The lowest perception is presented in the increase of physicians' commitment.

Resumen Introducción: la acreditación es un proceso de evaluación externo, sistemático, periódico y voluntario al que se someten instituciones de salud para demostrar el cumplimiento de niveles superiores de calidad en la atención. El Icontec, Instituto colombiano de normas técnicas, es la organización colombiana no gubernamental designada por el Ministerio de Salud para ser la entidad que acredita la calidad de las instituciones de salud en Colombia. El objetivo del presente estudio fue evaluar la percepción del valor que agrega la acreditación a la calidad de la atención en clínicas y hospitales en Colombia. Métodos: estudio transversal observacional. Se encuestaron 22 profesionales con experiencia en el proceso de acreditación Icontec. El instrumento evaluó tres ejes temáticos del proceso: valor agregado que aporta el proceso de acreditación, proceso de evaluación e informe final. La percepción de las fases del proceso fue medida a través de una escala tipo Likert y un análisis estadístico descriptivo. Resultados: los ítems con mejor percepción fueron la humanización de la atención (86.4%), la seguridad de los pacientes y el trabajo en equipo (81.8%). Laacreditación mejora la calidad de los procesos (77.4%), la prevención y el control de infecciones (68.1%) y el compromiso de los médicos (63.6%). El 54.6% consideró que los evaluadores utilizan métodos diferentes de evaluación. Conclusión: el sistema de acreditación Icontec en Colombia, agrega valor a las instituciones de salud en la mayoría de los ejes temáticos evaluados. La percepción más baja se presenta en el incremento de compromiso de los médicos.

Coronavirus (COVID 19) Infection in Pregnancy / Coronavirus (COVID 19) Infección en el embarazo

Abstract Coronavirus illness 2019 (COVID-19) is an airways infection caused by the new coronavirus (SARS-CoV-2) which has been quickly disseminated all over the world, affecting to the general population including women in pregnancy time. As being a recent infection, the evidence that supports the best practices for the management of the infection during pregnancy is limited, and most of the questions have not been completely solved yet. This publication offers general guidelines focused on decision-making people, managers, and health's teams related to pregnant women attention and newborn babies during COVID-19 pandemic. Its purpose is to promote useful interventions to prevent new infections as well as prompt and adequate attention to avoid serious complications or deaths, trying to be adapted to the different contexts in which attention to expectant mothers is provided. Guidelines are set within a well-scientific evidence and available recommendations up to date.

Resumen La enfermedad por coronavirus 2019 (COVID-19) es una infección de las vías respiratorias causada por un nuevo virus (SARS-CoV-2) que se ha diseminado rápidamente en el mundo, afectando a la población general, incluida la población de mujeres cursando un embarazo. Por ser una infección de aparición reciente, la información que soporta las mejores prácticas para el manejo de la infección durante la gestación es escasa y muchas de las preguntas no están completamente resueltas. Esta publicación brinda lineamientos generales orientados a tomadores de decisión, gerentes y equipos de salud en relación con el cuidado de mujeres gestantes y recién nacidos durante la pandemia por COVID 19. Su finalidad es promover intervenciones beneficiosas para prevenir nuevos contagios, y la atención oportuna y adecuada de la gestante para evitar complicaciones graves y/o muertes, adecuándose a los distintos contextos en los que se proporciona atención médica. Los lineamientos se enmarcan en la mejor información científica y las recomendaciones disponibles hasta la fecha.

Extreme Maternal Morbidity: a tracer event to improve the quality of obstetric care in Latin America / Morbilidad Materna Extrema: evento trazador para mejorar la calidad de la atención obstétrica en América Latina

Abstract This article reviews critical aspects that have had an impact on the implementation of epidemiological surveillance of extreme maternal morbidity, as a tracer event of quality maternal care at population and institutional level; taking into account that maternal mortality has been usually monitored, and its analysis allows interventions to avoid maternal death. Until 2015, very few countries had been able to meet the goals established in the Millennium Development Goals (MDGs), especially MDG 5 - improving maternal health. As of today, it is observed that maternal mortality rate is quite heterogeneous, with rates from 1 case per 100,000 live births in developed countries, to more than 100 cases per 100,000 live births in developing countries. Therefore, complementary strategies such as surveillance of the extreme maternal morbidity could offer a more effective alternative to identify and implement interventions that allow us to prevent mortality and strengthen the quality of obstetric care. In addition, the importance of extreme maternal morbidity as a quality tracer event is that, unlike what is observed with maternal mortality, this is an event that occurs more frequently, is anticipatory of death, and the surviving pregnant woman is the primary source of information.

Resumen Este artículo revisa aspectos críticos que han tenido incidencia en la implementación de la vigilancia epidemiológica de la morbilidad materna extrema, como un evento trazador de calidad del cuidado materno a nivel poblacional e institucional, ya que usualmente se ha monitoreado la mortalidad materna y su análisis permite realizar intervenciones para evitar la muerte materna. Para el año 2015, muy pocos países lograron cumplir las metas establecidas en los Objetivos de Desarrollo del Milenio (ODM), especialmente el ODM 5- mejorar la salud materna. Al día de hoy se observa que la tasa de mortalidad materna es bastante heterogénea con tasas desde 1 caso por 100,000 nacidos vivos en países desarrollados, hasta más de 100 casos por cada 100,000 nacidos vivos en países en vía de desarrollo. Por lo tanto, estrategias complementarias como la vigilancia de la mortalidad materna extrema podrían ofrecer una alternativa más eficaz para identificar e implementar intervenciones que nos permitan prevenir la mortalidad y fortalecer la calidad de atención obstétrica, a partir de información más confiable y sin esperar que ocurra una muerte materna.

Usefulness of 18F-Fluorocholine Positron Emission Tomography-Computed Tomography in Locating Lesions in Hyperparathyroidism: A Systematic Review.

IMPORTANCE: Identifying parathyroid glands correctly before a surgical procedure is essential to perform minimally invasive surgery. First-line tests with discordant or negative results underscore the need for more accurate imaging tests, thus decreasing the requirement for bilateral neck exploration or reintervention. OBJECTIVE: To review the available evidence to determine positive predictive value, negative predictive value, sensitivity, and specificity in clinical cases in which 18F-fluorocholine positron emission tomography-computed tomography (PET/CT) could be useful as a method to locate the lesions, and the benefits and controversial aspects of the method. EVIDENCE REVIEW: A search was conducted using the PubMed Central and Cochrane Library databases for studies published in English from July 26, 2014, to November 30, 2018, using the search terms 18 choline, 18F choline, 18F-choline, 18 fluorocholine PET CT, hyperparathyroidism, primary hyperparathyroidism, secondary hyperparathyroidism, tertiary hyperparathyroidism, persistent hyperparathyroidism, recurrent hyperparathyroidism, ectopic hyperparathyroidism, and parathyroid adenoma. Other inclusion criteria were reporting at least 1 of the following measurements: negative or positive predictive value, sensitivity, and specificity of 18F-fluorocholine PET/CT in the diagnosis of hyperparathyroidism (HPT). Exclusion criteria were language other than English, use of a tracer other than 18F-fluorocholine, reports of a single case, and studies not related to HPT. The Oxford Centre classifications for levels of evidence were used. FINDINGS: Sixteen studies fulfilled the inclusion criteria, comprising a total of 619 patients. Selected studies included 10 prospective cohort studies, 5 retrospective cohort studies, and 1 case series. Of the subtypes of HPT diagnosed using 18F-fluorocholine PET/CT, 579 were primary HPT, 22 were secondary HPT, 1 was tertiary HPT, and 7 were associated with multiple endocrine neoplasia type I. Pathologically, the neoplasms comprised 459 adenomas, 59 hyperplasia, and 19 double adenomas. CONCLUSIONS AND RELEVANCE: 18F-fluorcholine PET/CT may be indicated when results of first-line tests are negative or discordant and in challenging clinical situations where locating the source of HPT is difficult.

Usability, Acceptability, and Usefulness of an mHealth App for Diagnosing and Monitoring Patients With Breakthrough Cancer Pain.

BACKGROUND: Breakthrough pain is a major problem and a source of distress in patients with cancer. We hypothesized that health care professionals may benefit from a real-time mobile app to assist in the diagnosis and monitoring of breakthrough cancer pain (BTcP). OBJECTIVE: This study aimed to test the usability, acceptability, and usefulness in real-world practice of the mobile App INES·DIO developed for the management of patients with BTcP. METHODS: This study consisted of a survey of a multidisciplinary sample of 175 physicians who evaluated the mobile app after testing it with 4 patients with BTcP each (for a total of 700 patients). The digital profile of the physicians, use of the different resources contained in the app, usefulness of the resources, acceptability, usability, potential improvements, intention to use, and additional resources to add were recorded. RESULTS: Of the 175 physicians, 96% (168/175) were working in public hospitals. They had an average of 12 (SD 7) years of experience in BTcP and almost all (174/175, 99.43%) had an active digital profile. The Eastern Cooperative Oncology Group and Karnofsky performance scales, the Visual Analogue Scale, and the Davies algorithm to diagnose BTcP were the most frequently used tools with patients and were assessed as very useful by more than 80% (140/175) of physicians. The majority (157/175, 90%) answered that App INES·DIO was well designed and 94% (165/175) would probably or very probably recommend it to other colleagues. More than two-thirds indicated that the report provided by the app was worth being included in patients' clinical records. The most valued resource in the app was the recording of the number, duration, and intensity of pain flares each day and baseline pain control to enhance diagnosis of BTcP. Additional patient-oriented cancer pain educational content was suggested for inclusion in future versions of App INES·DIO. CONCLUSIONS: Our study showed that App INES·DIO is easy to use and useful for physicians to help diagnose and monitor breakthrough pain in patients with cancer. Participants suggested the implementation of additional educational content about breakthrough pain. They agreed on the importance of adding new clinical guidelines/protocols for the management of BTcP, improving their communication skills with patients, and introducing an evidence-based video platform that gathers new educational material on BTcP.

Nervio laríngeo inferior no recurrente tipo I / Type-1 non-recurrent inferior laryngeal nerve

La variante no recurrente del nervio laríngeo recurrente (NLR) tiene una frecuencia que oscila entre el 0,25 y el 0,99% según las diferentes series informadas. El NLNR (nervio laríngeo no recurrente) es consecuencia de un desarrollo embriológico anómalo del tronco epiaórtico. Se presenta el caso de una paciente con la variante tipo I del NLNR como hallazgo intraoperatorio durante una tiroidectomía total. El NLNR es un variante anatómica rara; debe pensarse siempre que se haya buscado exhaustivamente de forma reglada el nervio laríngeo inferior derecho sin localizarlo en su sitio anatómico habitual.

The non-recurrent laryngeal nerve (NRLN) is a variant of the recurrent laryngeal nerve (RLN) with an incidence between 0.25 and 0.99% according to the different series reported. The NRLN is consequence of a vascular anomaly during the embryological development of the epiaortic trunk. We report the case of a woman with type-1 NRLN as an intraoperative finding during total thyroidectomy. The NRLN is a rare anatomic variant that should be suspected when the right inferior RLN cannot be identified in the usual anatomic location after a standardized exploration.

A Multidisciplinary Consensus for Clinical Care and Research Needs for Sturge-Weber Syndrome.

BACKGROUND: Sturge-Weber syndrome is a neurocutaneous disorder associated with port-wine birthmark, leptomeningeal capillary malformations, and glaucoma. It is associated with an unpredictable clinical course. Because of its rarity and complexity, many physicians are unaware of the disease and its complications. A major focus moving ahead will be to turn knowledge gaps and unmet needs into new research directions. METHODS: On October 1-3, 2017, the Sturge-Weber Foundation assembled clinicians from the Clinical Care Network with patients from the Patient Engagement Network of the Sturge-Weber Foundation to identify our current state of knowledge, knowledge gaps, and unmet needs. RESULTS: One clear unmet need is a need for consensus guidelines on care and surveillance. It was strongly recommended that patients be followed by multidisciplinary clinical teams with life-long follow-up for children and adults to monitor disease progression in the skin, eye, and brain. Standardized neuroimaging modalities at specified time points are needed together with a stronger clinicopathologic understanding. Uniform tissue banking and clinical data acquisition strategies are needed with cross-center, longitudinal studies that will set the stage for new clinical trials. A better understanding of the pathogenic roles of cerebral calcifications and stroke-like symptoms is a clear unmet need with potentially devastating consequences. CONCLUSIONS: Biomarkers capable of predicting disease progression will be needed to advance new therapeutic strategies. Importantly, how to deal with the emotional and psychological effects of Sturge-Weber syndrome and its impact on quality of life is a clear unmet need.

Incidence of human papillomavirus-related oropharyngeal cancer and outcomes after chemoradiation in a population of heavy smokers.

BACKGROUND: Incidence of human papillomavirus (HPV)-related oropharyngeal carcinomas is increasing worldwide. The purpose of this study was to report the incidence in our region, and to determine the influence of HPV status on survival among a heavy smoking population. METHODS: p16 expression was analyzed in 102 patients with stage II to IV treated with chemoradiation. Overall survival (OS), locoregional control, and disease-free survival (DFS) were compared for HPV+ and HPV- status. RESULTS: The majority of patients were smokers (86%). p16 positivity was found in 26.7%. Patients who were HPV+ were younger (56 vs 59 years old; p = .052). No differences were observed regarding tumor stage, sex, or smoking between HPV+ and HPV-. Three-year OS was 67.4% for patients who were HPV+ versus 49.7% for HPV- (hazard ratio [HR], 0.55; p = .095). CONCLUSION: Incidence of HPV-related oropharyngeal carcinoma in Spain is similar to that reported in other European countries. In this sample of heavy smokers, we observed a nonsignificant trend for better outcomes in patients who were HPV+.

P53 and cellular glucose uptake.

OBJECTIVES: Tumor protein p53 is a transcription factor involved with cellular responses to stressors including limited glucose availability. We hypothesized that modulating p53 levels would affect cellular glucose uptake. METHODS AND RESULTS: Transfecting cultured primary mouse hepatocytes with p53 siRNA suppressed p53 mRNA expression >90%. Control hepatocytes (transfected with non-targeting siRNA) increased glucose uptake (2.28 ± 1.02-fold vs basal, p 0.009) in response to 100 nM insulin, but p53 siRNA-treated hepatocytes had a blunted response (0.92 ± 0.11-fold vs basal; between group difference p 0.0012). In adipocytes differentiated from the pre-adipocyte line 3T3-L1, knockdown of p53 had no effect on insulin-stimulated glucose uptake. There were no differences in Glut 1 or Glut 2 expression in the plasma membrane fraction or in the levels of phosphorylated AKT in cell lysates between primary hepatocytes transfected with p53 siRNA or control siRNA. Glycemic responses to insulin tolerance, glucose tolerance, and pyruvate tolerance tests did not differ between p53 knockout and wild type mice. DISCUSSION: Thus, inhibition of p53 has pleiotropic effects, inhibiting glucose uptake in the liver but having no effect on adipocytes. Knockout of p53 has no apparent effect on glucose homeostasis in intact lean mice. An explanation for the association between p53 expression and hepatocyte glucose uptake remains to be elucidated.

Epidemiology and prevalence of oropharyngeal candidiasis in Spanish patients with head and neck tumors undergoing radiotherapy treatment alone or in combination with chemotherapy.

OBJECTIVE: To describe the oropharyngeal candidiasis (OPC) prevalence in Spanish patients with head and neck cancer undergoing radiotherapy, alone or combined with chemotherapy. Secondary objectives were to determine the prevalence of Candida species colonization, and to explore whether different Candida species colonizing the oral cavity and the treatment were associated with a higher prevalence of OPC. METHODS: This is an observational, cross-sectional, multicentre study, conducted in Spanish radiation oncology units. Patients were diagnosed with head and neck cancer and started a radiotherapy treatment alone or combined with chemotherapy at the moment of their inclusion (N = 92). RESULTS: The OPC prevalence was 26 %. The identification of colonizing pathogens was performed in 49 patients, and Candida albicans was the dominant yeast (69 %), while non-albicans Candida was only found in 15 patients (31 %). Patients with C. albicans colonization had a significant higher prevalence of OPC compared to patients colonized by non-albicans Candida (p = 0.0273), but no difference was found regarding the OPC prevalence in patients receiving only radiotherapy compared to patients with both radiotherapy and chemotherapy treatments. CONCLUSIONS: Our data represent a step further in the knowledge of Candida species present in Spanish patients with head and neck tumors under radiation therapy. This is an essential step to manage the prophylaxis and treatment of OPC, since it might lead to severe clinical complications causing treatment interruption and, thus, representing a reduction in anti-tumor efficacy.

Cerebellar involvement in Hodgkin's lymphoma: an atypical site of relapse.

The presentation of intracranial metastases from Hodgkin's lymphoma is an infrequent event that worsens clinical outcome. A case of Hodgkin's lymphoma relapse in the cerebellum is described in a 70-year-old woman with a previously treated stage IVA Hodgkin's lymphoma. Diagnostic workup and treatment strategies for central nervous system relapses are reviewed and discussed. A combination of surgery, radiotherapy and occasionally chemotherapy remains the most appropriate approach to intracranial Hodgkin's lymphoma.

Chylothorax due to metastatic prostate carcinoma: an unusual complication.

Chylothorax, the abnormal accumulation of lymphatic fluid within the pleural space, is an infrequent complication of tumours affecting the mediastinum. The development of chylothorax is extraordinary in association with prostate cancer, although it has been described before. Adequate treatment of malignant chylothorax comprises both a conservative approach, including dietary and hormonal manipulations, and mechanic intercostal drainage that have been demonstrated to be effective in the management of chylothorax of malignant origin. Radiation therapy has been used for the treatment of neoplasic chylothorax but with inconsistent results. We present a new case of chylothorax associated to prostate adenocarcinoma and review the existing evidence for its treatment.

Radiochemotherapy with cisplatin and oral tegafur in advanced head and neck cancer: long-term results of a phase II study.

AIMS AND BACKGROUND: To evaluate the tolerance and efficacy of an original concurrent radiochemotherapy regimen in locally advanced head and neck cancer. METHODS: Sixty-four patients with stage III or IV squamous cell carcinoma arising from a head and neck mucosal site were eligible. Simultaneous radiochemotherapy consisted of two courses of continuous infusional cisplatin (20 mg/m2/d, days 1-4 and 29-32) and oral tegafur (1200 mg/d, days 1-14 and 29-43), together with conventional radiation therapy up to a total dose of 70-75 Gy over nine weeks. RESULTS: All the patients were evaluated for toxicity and response. Acute mucositis was the most prevalent complication. Grade 3 toxicities were mucositis (44%), skin toxicity (10%), leukopenia (8%), and thrombocytopenia (1%). No toxic death was observed. Complete response to treatment was observed in 72% of patients. With a median follow-up of 48.5 months (range, 27-84), 5-year actuarial rate of local-regional control, disease-free survival, overall survival and disease-specific survival were 60% (95% confidence interval [CI], 40-70%), 55% (95% CI, 45-65%), 51% (95% CI, 43-59%) and 61% (95% CI, 53-69%), respectively. CONCLUSIONS: Response, local-regional control and survival rates are equivalent to those reported from other concomitant radiochemotherapy combinations. However, the regimen offers the advantage of its tolerance and toxicity profile.

Metastatic disease from chordoma.

Chordomas are tumors with a bad prognosis, because of their location, local aggressiveness and high rate of local relapse. Despite of be benign tumors, they have certain capacity of metastasize and a clinical evolution that results interesting. When we analyzed our series with 35 chordomas studied and treated between 1975 and 2002, we found three patients that experienced a systemic dissemination.

In vitro radiosensitisation by trabectedin in human cancer cell lines.

PURPOSE: To examine the potential radiosensitising properties of trabectedin (ET-743, Yondelis). METHODS AND MATERIALS: In vitro chemosensitivity was assessed in four tumour cell lines (DU145, HeLa, HT29, HOP62) by the crystal violet method. IC10s and IC50s were established for 1-h, 24-h and 7-day (continuous) exposure times. Radiosensitisation was evaluated by conventional colony assay. BrdUrd DNA-labelling and flow cytometry were used to analyse cell cycle kinetics. The rate of apoptotic induction was assed by annexyn-V labelling. RESULTS: Mean IC50s were 18.8 nM (10.5 - 30), 2.5 nM (1.5 - 5) and 0.25 nM (0.2-0.8) for 1 h, 24 h and continuous exposure times, respectively. HT29 and HOP62 were the most sensitive cells lines to trabectedin. Radiosensitisation was observed in DU145 and HeLa cells with a dose enhancement factor (DEF) of 1.92 and 1.77 at IC50 dose level, respectively. Trabectedin induced early S phase arrest in all cell lines studied. CONCLUSIONS: Trabectedin, at pharmacologically appropriated concentrations, harbours a significant in vitro radiosensitising effect and induces cell cycle changes and apoptosis in several human cancer cell lines. Further studies to define the clinical potential of the combination of trabectedin and radiotherapy are needed.

Preoperative chemoradiotherapy for rectal cancer: randomized trial comparing oral uracil and tegafur and oral leucovorin vs. intravenous 5-fluorouracil and leucovorin.

PURPOSE: To compare, in a randomized trial, 5-fluorouracil (FU) plus leucovorin (LV) (FU+LV) vs. oral uracil and tegafur (UFT) plus LV (UFT+LV) given concomitantly with preoperative irradiation in patients with cT3-4 or N+ rectal cancer. METHODS AND MATERIALS: A total of 155 patients were entered onto the trial. Patients received pelvic radiotherapy (4500-5,040 cGy in 5 to 6 weeks) and chemotherapy consisting of two 5-day courses of 20 mg/m(2)/d LV and 350 mg/m(2)/d FU in the first and fifth weeks of radiotherapy (77 patients) or one course of 25 mg/d oral LV and 300 mg/m(2)/d UFT for 4 weeks beginning in the second week of radiotherapy (78 patients). The primary endpoints were pathologic complete response (pCR) and resectability rate. Secondary endpoints included downstaging rate, toxicity, and survival. RESULTS: Grade 3-5 acute hematologic toxicity occurred only with FU+LV (leukopenia 9%; p = 0.02). There were no differences in resectability rates (92.1% vs. 93.4%; p = 0.82). The pCR rate was 13.2% in both arms. Tumor downstaging was more frequent with UFT+LV (59.2% vs. 43.3%; p = 0.04). Three-year overall survival was 87% with FU+LV and 74% with UFT+LV (p = 0.37). The 3-year cumulative incidences of local recurrence were 7.5% and 8.9%, respectively (p = 0.619; relative risk, 1.46; 95% confidence interval 0.32-6.55). CONCLUSION: Although this study lacked statistical power to exclude clinically significant differences between both groups, the outcome of patients treated with UFT+LV did not differ significantly from that of patients treated with FU+LV, and hematologic toxicity was significantly lower in the experimental arm.