Carmen Lobo

Expression of Proteins Associated With Multidrug Resistance to Chemotherapy in Lung Cancer

OBJECTIVE: Membrane transporters are proteins that play a crucial role in resistance to chemotherapy. The aim of this study was to assess the influence of membrane transporter protein expression on chemotherapeutic response. MATERIAL AND METHODS: One hundred and forty seven samples of tumor tissue were collected from 143 patients; 35 samples were obtained by bronchoscopy and 112 were surgical specimens. A total of 101 samples from 99 patients were adequate for study. Cryopreserved samples were subjected to immunohistochemical analysis to detect 3 proteins associated with multidrug resistance: P-glycoprotein (Pgp), multidrugresistance‐associated protein 1 (MRP1), and lung resistance protein (LRP). RESULTS: In 16 cases none of the proteins were expressed. A single protein was expressed in 32 (3 Pgp, 11 MRP1, and 18 LRP); 2 in 34 cases (24 Pgp and LRP; 5 MRP1 and Pgp; 5 MRP1 and LRP); and all 3 in 17 cases. No significant relationship was found between age and the expression of Pgp (P=.74), MRP1 (P=.95), or LRP (P=.26). Nor were there significant differences in number (P=.72) or type of coexpressed proteins (P=.39) by sex, by tumor stage (number, P=.55; type, P=.21), or by tumor grade (number, P=.59; type, P=.51). There was a highly significant trend toward coexpression of Pgp and LRP (P<.01) but not of Pgp and MRP1 (P=.18) or MRP1 and LRP (P=.26). MRP1 was expressed less often in adenocarcinoma. LRP was expressed less often in squamous cell carcinoma than in adenocarcinoma and undifferentiated large cell carcinoma. Coexpression of Pgp, MRP1, and LRP was observed most often in squamous cell carcinoma. CONCLUSIONS: Proteins associated with multidrug resistance are commonly expressed in lung cancer. Of the 3 proteins studied, LRP was the one most often found. Coexpression of more than 1 of the proteins was found in a considerable percentage of patients. Pgp was mainly found to be coexpressed with LRP. Pgp expression and the number of coexpressed proteins seemed to have a negative impact on response to chemotherapy.

Síndrome de Stewart-Treves

Lymphangiosarcoma is an uncommon vascular tumor that usually develops in longstanding lymphedema. We gathered the cases of lymphangioma observed in a hospital and attempted to analyze their characteristics: age, sex, localization, treatment and follow-up data. We studied five cases: three cases of Stewart-Treves syndrome after mastectomy and radiotherapy and two cases that developed in patients with late-onset congenital lymphedema. There were four women and one man. Radical surgery was performed in four patients. The techniques employed were: above-knee amputation (one patient), hip disarticulation (one patient), scapulo-humeral disarticulation (two patients) and gemcitabine and radiotherapy in one patient with metastatic disease at diagnosis. Three patients died in the first 14 months of follow-up, while two are disease free after 46 and 86 months respectively. This study confirms the poor prognosis of patients with Steward-Treves syndrome.

Eritema anular eosinofílico

Resumen —. Introduccion. El eritema anular eosinofilico, inicialmente descrito en la infancia, es una rara enfermedad benigna y autolimitada que se caracteriza por la presencia de lesiones anulares eritematosas recurrentes, que normalmente se localizan en el tronco y las extremidades. El curso es recidivante con intervalos libres de enfermedad. El estudio histologico muestra en la dermis un infiltrado perivascular con linfocitos y eosinofilos. No suele detectarse eosinofilia en sangre periferica. Su etiologia es desconocida. El tratamiento con antipaludicos de sintesis ha demostrado ser eficaz en los 2 casos publicados. Un varon de 59 anos consulto por presentar papulas urticariales y lesiones anulares recurrentes, no pruriginosas, en el tronco, desde hacia 3 meses. La biopsia mostro un infiltrado linfocitico de predominio perivascular con eosinofilos en la dermis. La enfermedad remitio espontaneamente en 10 meses.

Factores predictores de respuesta y revisión de la toxicidad cutánea de cetuximab y panitumumab en 116 pacientes

INTRODUCTION AND OBJECTIVES Cetuximab and panitumumab are monoclonal antibodies that target the epidermal growth factor receptor (EGFR) in the treatment of metastatic colorectal cancer. Most patients develop a papulopustular rash, which may predict tumor response. We studied whether the other adverse cutaneous effects associated with these monoclonal antibodies are also clinical predictors of response. We also reviewed publications describing approaches to treating the papulopustular rash since no evidence-based guidelines have yet been published. MATERIAL AND METHODS We performed a retrospective study of 116 patients with metastatic colorectal cancer receiving anti-EGRF therapy with cetuximab or panitumumab at Hospital Universitario Donostia. RESULTS In total, 81.9% of the patients developed a papulopustular rash. Patients who received the most cycles of treatment with the EGFR inhibitor were at the highest risk of developing the rash, and these patients also had the most severe rash reactions (P=.03). All of the patients who exhibited a complete tumor response had the rash, and the incidence of rash was lower in patients with poor tumor response (P=.03). We also observed an association between tumor response and xerosis (53.4% of the patients who developed xerosis also exhibited tumor response, P=.002). The papulopustular rash was managed according to an algorithm developed by our department. CONCLUSIONS Severe papulopustular rash and xerosis may be clinical predictors of good response to anti-EGFR therapy. Patients who develop a papulopustular rash should be treated promptly because suboptimal treatment of this and other adverse effects can lead to delays in taking the prescribed anti-EGFR dose or to interruption of therapy.

The Presence of Mutations in the K-RAS Gene Does Not Affect Survival after Resection of Pulmonary Metastases from Colorectal Cancer

Introduction. Our objective was to identify mutations in the K-RAS gene in cases of pulmonary metastases from colorectal cancer (CRC) and determine whether their presence was a prognostic factor for survival. Methods. We included all patients with pulmonary metastases from CRC operated on between 1998 and 2010. K-RAS mutations were investigated by direct sequencing of DNA. Differences in survival were explored with the Kaplan-Meier method log-rank tests and multivariate Cox regression analysis. Results. 110 surgical interventions were performed on 90 patients. Factors significantly associated with survival were disease-free interval (P = 0.002), age (P = 0.007), number of metastases (P = 0.001), lymph node involvement (P = 0.007), size of the metastases (P = 0.013), and previous liver metastasis (P = 0.003). Searching in 79 patients, K-RAS mutations were found in 30 cases. We did not find statistically significant differences in survival (P = 0.913) comparing native and mutated K-RAS. We found a higher rate of lung recurrence (P = 0.040) and shorter time to recurrence (P = 0.015) in patients with K-RAS mutations. Gly12Asp mutation was associated with higher recurrence (P = 0.022) and lower survival (P = 0.389). Conclusions. The presence of K-RAS mutations in pulmonary metastases does not affect overall survival but is associated with higher rates of pulmonary recurrence.

Determinación de grupo de bajo riesgo para tener nódulos metastásicos no detectados por tomografía axial computarizada en la cirugía de las metástasis pulmonares

INTRODUCTION In recent years, there has been debate regarding the diagnostic accuracy of computed tomography (CT) in the identification of lung metastases and the need for lung palpation to determine the number of metastatic nodules. The aim of this study was to determine in which patients the CT scan was more effective in detecting all metastases. METHODS We studied all patients who underwent curative thoracotomy for pulmonary metastasis between 1998 and 2012. All cases were reviewed by two expert pulmonary radiologists before surgery. Statistical analyses were performed using Systat version 13. RESULTS The study included 183 patients (63.6% male) with a mean age of 61.7 years who underwent 217 interventions. The CT scan was correct in 185 cases (85.3%). Discrepancies observed: 26 patients (11.9%) with more metastases resected than observed and 6 cases (2.8%) with fewer metastases. In patients with one or two metastases of colorectal origin or a single metastasis of any other origin, the probability of finding extra nodules was 9.5%. In the remaining patients, the probability was 27.8%, with statistically significant differences (P=.001). The mean age of the patients in whom no unobserved nodules were detected was 62.9 years compared to 56.5 years on average in patients who were free from any metastases (P=.001). CONCLUSIONS Patients older than 60 years, with one or two metastases of colorectal origin or a single metastasis from any other origin were considered to be the group with low probability of having more metastases resected than observed.