A case of capecitabine-induced coronary microspasm in a patient with rectal cancer

5-Fluorouracil (5-FU) is the most frequently used chemotherapy agent concomitant with radiotherapy in the management of patients with rectal cancer. Capecitabine is an oral fluoropyrimidine that mimics the pharmaconkinetics of infusional 5-FU. This new drug is replacing 5-FU as a part of the combined-modality treatment of a number of gastrointestinal cancers. While cardiac events associated with the use of 5-FU are a well known side effect, capecitabine-induced cardiotoxicity has been only rarely reported. Here, we reviewed the case of a patient with rectal cancer who had a capecitabine-induced coronary vasospasm. The most prominent mutation of the dihydropyrimidine dehydrogenase gene was also analyzed

Student's Inventory of Professionalism (SIP): A tool to assess attitudes towards professional development based on palliative care undergraduate education

Introduction: Quality medical education, centered on a patient's needs, is crucial to develop the health professionals that our society requires. Research suggests a strong contribution of palliative care education to professionalism. The aim of this study was to design and validate a self-report inventory to measure student's professional development. Method: Sequential exploratory strategy mixed method. The inventory is built based on the themes that emerged from the analysis of four qualitative studies about nursing and medical students' perceptions related to palliative care teaching interventions (see Ballesteros et al. 2014, Centeno et al. 2014 and 2017, Rojí et al. 2017). The structure and psychometrics of the inventory obtained is tested in two different surveys with two different groups of medical students. Inventory reliability and construct validity are tested in the first survey group. To verify the inventory structure, a confirmatory factor analysis is performed in a second survey group. Results: The inventory has 33 items and seven dimensions: a holistic approach, caring for and understanding the patient, personal growth, teamwork, decision-making, patient evaluation, and being a health care professional. Cronbach's-alpha was 0.73-0.84 in all seven domains, ICC: 0.95. The confirmatory factor analysis comparative fit index (CFI) was 1 with a standardized root mean square Index 0.088 (SRMR) and obtained a 0.99 goodness-of-fit R-square coefficient. Conclusions: this new inventory is grounded on student's palliative care teaching experiences and seems to be valid to assess student's professional development

Educación interprofesional: una propuesta de la Universidad de Navarra

La asistencia sanitaria centrada en el paciente es la clave para una atención humana a la persona y a su familia. La práctica colaborativa en equipos interprofesionales resulta imprescindible para alcanzar una atención sanitaria de calidad. La universidad tiene la responsabilidad de preparar a sus graduados para trabajar en equipos interprofesionales. Una enseñanza/aprendizaje centrada en la persona, fundamentada en las competencias que definen la educación interprofesional, es clave para que nuestros estudiantes reconozcan la necesidad del trabajo colaborativo. Este artículo detalla un proyecto docente de educación interprofesional de la Universidad de Navarra, donde estudiantes de las facultades de medicina, enfermería y farmacia aprenden juntos y de manera gradual, las claves de cómo trabajar en equipo

La educación interprofesional en la universidad: retos y oportunidades

La educación interprofesional (EIP) es clave para garantizar el aprendizaje integrado de los alumnos de diferentes titulaciones, que ejercerán una labor profesional basada en el cuidado centrado en la persona, de manera conjunta. El proyecto de EIP de la Universidad de Navarra pretende dar a los alumnos de medicina, enfermería y farmacia los conocimientos, habilidades y actitudes necesarias para trabajar de manera interprofesional, centrándonos en trabajo en equipo, conocimiento y respeto de roles, resolución de conflictos y comunicación interprofesional. Para ello, el equipo de docentes implicados en este proyecto ha tenido que trabajar colaborativamente, experimentando las claves de este trabajo interprofesional, centrado en el alumno, constituyendo una experiencia enriquecedora, constructiva, y que ha aportado las claves del trabajo en equipo necesario para llevar a cabo un proyecto docente de EIP.Interprofessional Education is key to guarantee the integrated learning to different students, who will exercise together a professional work based on a person-centred care. The EIP project of the University of Navarra aims to provide to medical, nursing and pharmacy students with the knowledge, skills and attitudes necessary to work interprofessionally focu- sing on teamwork, knowledge and respect for roles, conflict resolution and interprofessional communication. To achieve this aim, the teachers from the different faculties involved in this project has worked collaboratively, experiencing the keys of this interprofessional work focused on the student, constituting an enriching, living a constructive experience and contributing to the cornerstone of the teamwork necessary to undertake an EIP teaching project

Impact of perineural invasion on the outcome of patients with synchronous colorectal liver metastases treated with neoadjuvant chemotherapy and surgery

Purpose: To analyze the prognostic value of variables of the primary tumor in patients with synchronous liver metastases in colorectal cancer (CLRMs) treated with neoadjuvant chemotherapy and surgery. Methods/patients: From a prospective database, we retrospectively identified all patients with synchronous CLRMs who were treated with neoadjuvant chemotherapy and liver resection. Using univariate and multivariate analyses, we identified the variables associated with tumor recurrence. Overall survival and disease-free survival were calculated using the Kaplan-Meier method with differences determined by the Cox multiple hazards model. Results were compared using the log-rank test. Results: Ninety-eight patients with synchronous CLRMs were identified. With a median follow-up of 39.8 months, overall survival and disease-free survival at 5 and 10 years were 53%, 41.7%, 29% and 29%, respectively. Univariate analysis identified three variables associated with tumor recurrence: location in the colon (p = 0.025), lymphovascular invasion (p = 0.011) and perineural invasion (p = 0.005). Multivariate analysis identified two variables associated with worse overall survival: perineural invasion (HR 2.36, 95% CI 1.162-4.818, p = 0.018) and performing frontline colectomy (HR 3.286, 95% CI 1.256-8.597, p = 0.015). Perineural invasion remained as the only variable associated with lower disease-free survival (HR 1.867, 95% CI 1.013-3.441, p = 0.045). Overall survival at 5 and 10 years in patients with and without perineural invasion was 68.2%, 54.4% and 29.9% and 21.3%, respectively (HR 5.920, 95% CI 2.241-15.630, p < 0.001). Conclusions: Perineural invasion in the primary tumor is the variable with most impact on survival in patients with synchronous CLRMs treated with neoadjuvant chemotherapy and surgery

Hypofractionated radiation therapy and temozolomide in patients with glioblastoma and poor prognostic factors. A prospective, single-institution experience

Background: Hypofractionated radiation therapy is a feasible and safe treatment option in elderly and frail patients with glioblastoma. The aim of this study was to evaluate the effectiveness of hypofractionated radiation therapy with concurrent temozolomide in terms of feasibility and disease control in primary glioblastoma patients with poor prognostic factors other than advanced age, such as post-surgical neurological complications, high tumor burden, unresectable or multifocal lesions, and potential low treatment compliance due to social factors or rapidly progressive disease. Material and methods: GTV included the surgical cavity plus disease visible in T1WI-MRI, FLAIR-MRI and in the MET-uptake. The CTV was defined as the GTV plus 1.5-2 cm margin; the PTV was the CTV+0.3 cm margin. Forty, fourty-five, and fifty grays in 15 fractions were prescribed to 95% of PTV, CTV, and GTV, respectively. Treatment was delivered using IMRT or the VMAT technique. Simultaneously, 75 mg/m2/day of temozolomide were administered. Results: Between January 2010 and November 2017, we treated a total of 17 patients. The median age at diagnosis was 68-years; median KPS was 50-70%. MGMT-methylation status was negative in 5 patients, and 8 patients were IDH-wildtype. Eight of 18 patients were younger than 65-years. Median tumor volume was 26.95cc; median PTV volume was 322cc. Four lesions were unresectable; 6 patients underwent complete surgical resection. Median residual volume was 1.14cc. Progression-free survival was 60% at 6 months, 33% at 1-year and 13% at 2-years (median OS = 7 months). No acute grade 3-5 toxicities were documented. Symptomatic grade 3 radiation necrosis was observed in one patient. Conclusions: Patients with poor clinical factors other than advanced age can be selected for hypofractionated radiotherapy. The OS and PFS rates obtained in our series are similar to those in patients treated with standard fractionation, assuring good treatment adherence, low rates of toxicity and probable improved cost-effectiveness

Radioterapia estereotáctica

La radioterapia con técnica estereotáctica es una modalidad de radioterapia externa que utiliza un sistema de coordenadas tridimensionales independientes del paciente para la localización precisa de la lesión. También se caracteriza porque los haces de irradiación son altamente conformados, precisos y convergentes sobre la lesión que hacen posible la administración de dosis muy altas de radioterapia sin incrementar la irradiación de los órganos o estructuras sanas adyacentes. Cuando el procedimiento se realiza en una sesión de tratamiento se denomina radiocirugía y si se administra en varias sesiones se denomina radioterapia estereotáctica. Se precisa de sistemas de fijación e inmovilización del paciente especiales (guías o marcos estereotácticos) y dispositivos de radioterapia capaces de generar haces muy conformados (acelerador lineal, gammaknife, cyberknife, tomoterapia, ciclotrones). La radioterapia estereotáctica moderna utiliza marcas radioopacas intratumorales o sistemas de imágenes de TAC incluidos en el dispositivo de irradiación, que permiten una precisa localización de las lesiones móviles en cada sesión de tratamiento. Además, los avances tecnológicos hacen posible coordinar los movimientos de la lesión en la respiración con la unidad de radioterapia (gaiting y tracking) de forma que pueden estrecharse al máximo los márgenes y por lo tanto excluir un mayor volumen de tejido sano La radiocirugía está indicada principalmente en lesiones cerebrales benignas o malignas menores de 3-4 centímetros (malformaciones arteriovenosas, neurinomas, meningiomas, metástasis cerebrales) y la radioterapia estereotáctica se administra fundamentalmente en tumores de localización extracraneal que requieran una alta conformación y precisión como cáncer precoz de pulmón inoperable y metástasis hepáticas.Stereotactic radiotherapy is an external radiation modality that uses a system of three dimensional references independent of the patient to achive a precise location of the lesion. Stereotactic radiotherapy generate highly conformal, precisely focused radiation beams to administer very high doses of radiation without increasing the radiation to healthy surrounding organs or structures. When the procedure is carried out in one treatment session the procedure is termed radiosurgery, and when the treatment is administered in several fractions, the radiation modality is termed stereotactic radiotherapy. Special systems of patient immobilization (guides or stereotactic frames) are required together with radiotherapy devices capable of generating conformal beams (lineal accelerator, gammaknife, cyberknife, tomotherapy, cyclotrons). Modern stereotactic radiotherapy techniques employ intratumoural radio-opaque fiducials or CT image systems included in the irradiation device, which make possible a precise location of mobile lesions in each treatment session. Besides, technological advances permit breathing synchronized radiation (gating and tracking) for maximum tightening of margins and excluding a greater volume of healthy tissue. Radiosurgery is mainly indicated in benign or malign cerebral lesions less than 3-4 centimetres (arteriovenous malformations, neurinomas, meningiomas, cerebral metastases) and stereotactic radiotherapy is basically administered in tumours of extracraneal location that require high conformation and precision, such as inoperable early lung cancer and liver metastasis

Therapeutic drug monitoring of neoadjuvant mFOLFIRINOX in resected pancreatic ductal adenocarcinoma

Background: Despite a potentially curative treatment, the prognosis after upfront surgery and adjuvant chemotherapy for patients with resectable pancreatic ductal adenocarcinoma (PDAC) is poor. Modified FOLFIRINOX (mFOLFIRINOX) is a cornerstone in the systemic treatment of PDAC, including the neoadjuvant setting. Pharmacokinetic-guided (PKG) dosing has demonstrated beneficial effects in other tumors, but scarce data is available in pancreatic cancer. Methods: Forty-six patients with resected PDAC after mFOLFIRINOX neoadjuvant approach and included in an institutional protocol for anticancer drug monitoring were retrospectively analyzed. 5-Fluorouracil (5-FU) dosage was adjusted throughout neoadjuvant treatment according to pharmacokinetic parameters and Irinotecan (CPT-11) pharmacokinetic variables were retrospectively estimated. Results: By exploratory univariate analyses, a significantly longer progression-free survival was observed for patients with either 5-FU area under the curve (AUC) above 28 mcg$h/mL or CPT-11 AUC values below 10 mcg$h/mL. In the multivariate analyses adjusted by age, gender, performance status and resectability after stratification according to both pharmacokinetic parameters, the risk of progression was significantly reduced in patients with 5-FU AUC 28 mcg$h/mL [HR ¼ 0.251, 95and CPT-11 AUC <10 mcg$h/mL [HR ¼ 0.189, 95% CI 0.073e0.486, p ¼ 0.001]. Conclusions: Pharmacokinetically-guided dose adjustment of standard chemotherapy treatments might improve survival outcomes in patients with pancreatic ductal adenocarcinoma

Use of Machine-Learning Algorithms in Intensified Preoperative Therapy of Pancreatic Cancer to Predict Individual Risk of Relapse

Background: Although surgical resection is the only potentially curative treatment for pancreatic cancer (PC), long-term outcomes of this treatment remain poor. The aim of this study is to describe the feasibility of a neoadjuvant treatment with induction polychemotherapy (IPCT) followed by chemoradiation (CRT) in resectable PC, and to develop a machine-learning algorithm to predict risk of relapse. Methods: Forty patients with resectable PC treated in our institution with IPCT (based on mFOLFOXIRI, GEMOX or GEMOXEL) followed by CRT (50 Gy and concurrent Capecitabine) were retrospectively analyzed. Additionally, clinical, pathological and analytical data were collected in order to perform a 2-year relapse-risk predictive population model using machine-learning techniques. Results: A R0 resection was achieved in 90% of the patients. After a median follow-up of 33.5 months, median progression-free survival (PFS) was 18 months and median overall survival (OS) was 39 months. The 3 and 5-year actuarial PFS were 43.8% and 32.3%, respectively. The 3 and 5-year actuarial OS were 51.5% and 34.8%, respectively. Forty-percent of grade 3-4 IPCT toxicity, and 29.7% of grade 3 CRT toxicity were reported. Considering the use of granulocyte colony-stimulating factors, the number of resected lymph nodes, the presence of perineural invasion and the surgical margin status, a logistic regression algorithm predicted the individual 2-year relapse-risk with an accuracy of 0.71 (95% confidence interval [CI] 0.56-0.84, p = 0.005). The model-predicted outcome matched 64% of the observed outcomes in an external dataset. Conclusion: An intensified multimodal neoadjuvant approach (IPCT + CRT) in resectable PC is feasible, with an encouraging long-term outcome. Machine-learning algorithms might be a useful tool to predict individual risk of relapse. A small sample size and therapy heterogeneity remain as potential limitations

Factor von Willebrand como intermediario entre la hemostasia y la angiogénesis de origen tumoral

Cancer patients often show an imbalance condition between coagulation system and fibrinolysis which causes a prothrombotic state. Different molecular factors like von Willebrand factor (vWf), presenting higher plasmatic rates in these patients, play an important role in this situation. During active angiogenesis taking place in tumor growth, the vascular endothelial growth factor (VEGF) and the fibroblast growth factor (FGF-2) contribute to the proliferation and differentiation of endothelial tissue, the main vWf producer, promoting increased rates of vWf in the serum of neoplastic patients. Recently vWf's contribution to tumor cells and platelet adhesion has been described. In this process, the discovery of platelet, endothelial and tumor cell membrane integrins and their implication in cellular adhesion has represented a major step in demonstrating how blood clotting and platelet aggregation are mediated by tumor cell and platelet linkage. Migration properties acquired by tumor cells as a result of this binding have been also pointed out. Clinical trials show higher rates of plasmatic vWf in cancer patients the more advanced clinical and radiological stage they present (metastasic versus localized). Moreover, higher pre-surgical serum vWf rates in patients can be used to predict poorer survival after resection surgery. vWf high molecular weight multimers have been also related to a cleavage protease deficiency in the serum of the oncologic population. The promising results of antiaggregation/anticoagulation therapies in these patients permit us to envisage new therapeutic target