Genetic Polymorphisms and Tumoral Mutational Profiles over Survival in Advanced Colorectal Cancer Patients: An Exploratory Study.

Colorectal cancer is a common disease, both in Chile and worldwide. The most widely used chemotherapy schemes are based on 5-fluorouracil (5FU) as the foundational drug (FOLFOX, CapeOX). Genetic polymorphisms have emerged as potential predictive biomarkers of response to chemotherapy, but conclusive evidence is lacking. This study aimed to investigate the role of genetic variants associated with 5FU-based chemotherapy on therapeutic response, considering their interaction with oncogene mutations (KRAS, NRAS, PI3KCA, AKT1, BRAF). In a retrospective cohort of 63 patients diagnosed with metastatic colorectal cancer, a multivariate analysis revealed that liver metastases, DPYD, ABCB1, and MTHFR polymorphisms are independent indicators of poor prognosis, irrespective of oncogene mutations. BRAF wild-type status and high-risk drug-metabolism polymorphisms correlated with a poor prognosis in this Chilean cohort. Additionally, findings from the genomics of drug sensitivity (GDSC) project demonstrated that cell lines with wild-type BRAF have higher IC50 values for 5-FU compared to BRAF-mutated cell lines. In conclusion, the genetic polymorphisms DPYDrs1801265, ABCB1rs1045642, and MTHFRrs180113 may serve as useful biomarkers for predicting a poor prognosis in patients undergoing 5-fluorouracil chemotherapy, regardless of oncogene mutations.

Structure-Related Mechanical Properties and Bioactivity of Silica-Gelatin Hybrid Aerogels for Bone Regeneration.

We report the synthesis of mesoporous silica-gelatin hybrid aerogels with 15, 25, and 30 wt. % gelatin contents, using 3-glycidoxypropyl trimethoxysilane (GPTMS) as a coupling agent, for tissue-engineering applications. Aerogels were obtained using a one-step sol-gel process followed by CO2 supercritical drying, resulting in crack-free monolith samples with bulk densities ranging from 0.41 g cm-3 to 0.66 g cm-3. Nitrogen adsorption measurements revealed an interconnected mesopore network and a general decrease in the textural parameters: specific surface areas (651-361 m2 g-1), pore volume (1.98-0.89 cm3 g-1), and pore sizes (10.8-8.6 nm), by increasing gelatin content. Thermogravimetric analysis (TGA), Fourier-transform infrared (FTIR) spectroscopy and uniaxial compression experiments confirmed that the structure, thermal properties and mechanical behavior of these aerogels changed significantly when the concentration of gelatin reached 25 wt.%, suggesting that this composition corresponds to the percolation threshold of the organic phase. In addition, the samples exhibited hydrophilic behavior and extremely fast swelling in phosphate-buffered saline (PBS), with swelling ratios from 2.32 to 3.32. Furthermore, in vitro bioactivity studies revealed a strong relationship between the kinetics of the nucleation and growth processes of hydroxyapatite in simulated body fluid (SBF) and the gelatin content. The live/dead assay revealed no cytotoxicity in HOB® osteoblasts in vitro and a positive influence on cell growth, focal adhesion development, and cytoskeletal arrangement for cell adhesion. Mineralization assays confirmed the positive effects of the samples on osteoblast differentiation. The biomaterials described are versatile, can be easily sterilized and are suitable for a wide range of applications in bone tissue-engineering, either alone or in combination with bioactive-reinforced phases.

Predicting response to immune checkpoint blockade in NSCLC with tumour-only RNA-seq.

BACKGROUND: Targeted RNA sequencing (RNA-seq) from FFPE specimens is used clinically in cancer for its ability to estimate gene expression and to detect fusions. Using a cohort of NSCLC patients, we sought to determine whether targeted RNA-seq could be used to measure tumour mutational burden (TMB) and the expression of immune-cell-restricted genes from FFPE specimens and whether these could predict response to immune checkpoint blockade. METHODS: Using The Cancer Genome Atlas LUAD dataset, we developed a method for determining TMB from tumour-only RNA-seq and showed a correlation with DNA sequencing derived TMB calculated from tumour/normal sample pairs (Spearman correlation = 0.79, 95% CI [0.73, 0.83]. We applied this method to targeted sequencing data from our patient cohort and validated these results against TMB estimates obtained using an orthogonal assay (Spearman correlation = 0.49, 95% CI [0.24, 0.68]). RESULTS: We observed that the RNA measure of TMB was significantly higher in responders to immune blockade treatment (P = 0.028) and that it was predictive of response (AUC = 0.640 with 95% CI [0.493, 0.786]). By contrast, the expression of immune-cell-restricted genes was uncorrelated with patient outcome. CONCLUSION: TMB calculated from targeted RNA sequencing has a similar diagnostic ability to TMB generated from targeted DNA sequencing.

Immunotherapy in Advanced NSCLC Without Driver Mutations: Available Therapeutic Alternatives After Progression and Future Treatment Options.

The treatment paradigm of non-small-cell lung cancer without oncogenic drivers has varied dramatically in recent years and is constantly evolving. Immune- checkpoint inhibitors have demonstrated unprecedented durable efficacy in a subset of these patients, so these drugs have become the standard of care in most cases. There are different ways to deliver these agents, such as monotherapy and combinations of immunotherapy or chemotherapy plus immunotherapy. Treatment selection is complicated by an absence of head-to-head comparisons in randomized trials because these agents have gained approval by demonstrating superiority to platinum-doublet chemotherapy alone. Unfortunately, most patients will progress and die from their disease despite advances. Furthermore, after progression on these agents, there is a lack of randomized controlled data to support further management, constituting an unmet need. This review discusses the therapeutic alternatives after progression, summarizes mechanisms of resistance and progression patterns, and describes the main approaches under clinical investigation in the field.

[Update on neuroendocrine tumors]. / Tumores Neuroendocrinos: un desafío transversal.

Neuroendocrine Tumors (NETs) encompass a wide variety of tumors arising from neuroendocrine cells, which produce bioactive substances. The incidence of NETs increased significantly lately, becoming one of the most common tumors of the digestive tract. Their clinical presentation is as diverse as their capacity for hormone production. Carcinoid syndrome is the most common hormonal syndrome produced by NETs and is characterized by diarrhea, flushing and cardiac valvular lesions. New research brought multiple changes in the classification of these neoplasms and a new understanding about their diagnosis and treatment, promoting a multidisciplinary approach. Somatostatin analogues, radiation, biological, and cytotoxic drugs have improved the prognosis of these patients, which entails a great challenge for healthcare providers.

Immunotherapy in oncogene addicted non-small cell lung cancer.

The use of immune checkpoint inhibitors (ICIs) targeting the programmed cell death-1 (PD-1) and programmed cell death ligand-1 (PD-L1) has led to notable changes in treatment strategies for patients with advanced non-small cell lung cancer (NSCLC) and now forms a part of standard of care treatment in patients with advanced disease. However, most patients do not respond to ICI monotherapy, which may be explained by significant variations in efficacy according to different immune and molecular profiles in tumours. Improved response rates have been observed in smokers and are associated with tumors that have high mutation loads, with a higher tendency to form neoantigens. This premise itself defies the eventual significance of ICIs for oncogene-driven NSCLC, which in general are more common in never smokers and potentially have reduced capacity for neoantigen formation. Furthermore, pivotal trials investigating ICIs in advanced NSCLC have usually excluded patients with oncogenic drivers, hence the outcome of these agents in this population is poorly characterized. In this article, we aim to review the most current evidence, encompassing clinical and preclinical data focused on a wide range of oncogene-addicted NSCLCs.

EGFR Exon 20 Insertion Mutations: Clinicopathological Characteristics and Treatment Outcomes in Advanced Non-Small Cell Lung Cancer.

BACKGROUND: Epidermal growth factor receptor gene (EGFR) exon 20 insertion (ex20-ins) mutations are an uncommon and heterogeneous group of non-small cell lung cancers (NSCLCs), resistant to conventional EGFR tyrosine kinase inhibitors (TKIs). Characteristics and outcomes of patients with EGFR ex20-ins have not been fully established; we sought to clarify them using a multinational patient database. PATIENTS AND METHODS: Patients with NSCLC from six Australian institutions with EGFR exon 20 mutations (ex20-mut), excluding T790M, were retrospectively reviewed. Clinical characteristics and outcomes with systemic treatments were collected and analyzed using comparative statistics. RESULTS: Among 109 patients with ex20-mut, 61% were females and 75% were Caucasians. More males presented with de novo metastatic disease (84% vs. 51%; P = .002). Central nervous system (48%) and liver (24%) metastases were common within metastatic patients (n = 86). Thirty-nine patients received platinum-based chemotherapy (PBC) and achieved a 43% objective response rate (ORR), median progression-free survival (mPFS) of 6.9 months, and median overall survival (mOS) of 31.0 months. Twenty-three of the patients with ex20-ins received conventional TKIs, resulting in an ORR of 13%, mPFS of 3.4 months (95% confidence interval [CI], 1.91-6.25), and mOS of 31.0 months (95% CI, 15.09-not reached). Nine patients with S786I mutations received TKIs, resulting in an ORR of 50%, mPFS of 18.2 months (2.79-not reached), and mOS of 33.4 months (95% CI, 16.14-not reached). Twenty-three patients received immune checkpoint inhibitor monotherapy (ICIm), resulting in an ORR of 4%, mPFS of 2.6 months (95% CI, 1.91-4.83), and mOS of 30.8 months (95% CI, 17.62-41.62). CONCLUSION: Although phenotypically similar to patients with common EGFR mutations, patients with EGFR ex20-mut had worse survival, perhaps due to the lack of targeted therapies. Chemotherapy was superior to conventional EGFR TKIs in patients with EGFR ex20-ins, although there was moderate activity of TKIs in S768I mutations. ICIm was ineffective.

Tumores Neuroendocrinos: un desafío transversal / Update on neuroendocrine tumors

Neuroendocrine Tumors (NETs) encompass a wide variety of tumors arising from neuroendocrine cells, which produce bioactive substances. The incidence of NETs increased significantly lately, becoming one of the most common tumors of the digestive tract. Their clinical presentation is as diverse as their capacity for hormone production. Carcinoid syndrome is the most common hormonal syndrome produced by NETs and is characterized by diarrhea, flushing and cardiac valvular lesions. New research brought multiple changes in the classification of these neoplasms and a new understanding about their diagnosis and treatment, promoting a multidisciplinary approach. Somatostatin analogues, radiation, biological, and cytotoxic drugs have improved the prognosis of these patients, which entails a great challenge for healthcare providers.

NTRK and ALK rearrangements in malignant pleural mesothelioma, pulmonary neuroendocrine tumours and non-small cell lung cancer.

OBJECTIVES: Gene rearrangements involving NTRK1, NTRK2, NTRK3, ROS1 and ALK have been identified in many types of cancer, including non-small cell lung cancer (NSCLC). Data in malignant pleural mesothelioma (MPM), lung neuroendocrine tumors (NETs) and small-cell lung cancer (SCLC) are lacking. Given the activity of NTRK, ROS-1 and ALK inhibitors in tumors harboring gene fusions, we sought to explore such rearrangements in these less common tumors in addition to NSCLC. METHODS: Archival tumor tissue from patients with MPM, lung NETs, SCLC and NSCLC were used to create tissue microarrays. Immunohistochemistry (IHC) was performed using a cocktail of antibodies against TRK, ROS1 and ALK. IHC positive samples underwent RNA sequencing using the ArcherDX FusionPlex CTL diagnostic assay. Clinical data were obtained through retrospective chart review. RESULTS: We performed IHC on 1116 samples: 335 MPMs, 522 NSCLCs, 105 SCLCs and 154 lung NETs. There were 23 IHC positive cases (2.1%) including eight MPMs (2.4%), eight NETs (5.2%), five SCLC (4.8%) and two NSCLC (0.4%). The following fusions were detected: one MPM with an NTRK ex10-TPM3 ex8, another MPM with an ALK ex20-EML4ex13, one lung intermediate-grade NET (atypical carcinoid) with an ALK ex20-EML4 ex6/intron6, and two NSCLCs with an ALK ex20-EML4 ex6/intron6 rearrangement. None of the patients received targeted treatment. CONCLUSIONS: To our knowledge, we report for the first time NTRK and ALK rearrangements in a small subset of MPM. An ALK rearrangement was also detected in lung intermediate-grade NET (or atypical carcinoid). Our data suggest that IHC could be a useful screening test in such patients to ensure that all therapeutic strategies including targeted therapy are utilized.

Regorafenib adjusted dose for Chilean patients with chemoresistant metastatic colorectal cancer: a case series.

BACKGROUND: Regorafenib is a therapeutic alternative for patients with metastatic colorectal cancer (MCRC) resistant to conventional therapies. The reported toxicity is relevant and there is no data on Latin American patients. The objective was to evaluate the overall survival (OS), progression-free survival (PFS) and quality of life (QoL) in a prospective cohort of Latin American patients treated with an adjusted dose of regorafenib. METHODS: We prospectively recruited patients with MCRC that progressed to standard therapy. A dose escalation algorithm was used. OS, PFS, response rate and QoL were evaluated. RESULTS: We recruited 13 patients between June and November 2015. The median age was 60 years. Median OS was 8.6 months and median PFS was 2.2 months. The response rate was 8%. Grade 3-4 toxicities included grade 3 palmoplantar erythrodysesthesia in 23% and grade 3 fatigue in 12% of patients. CONCLUSION: Regorafenib treatment is effective in Latin American patients with conventional therapy resistant MCRC.

Experiencia inicial en seguridad, tolerancia y adherencia al uso de docetaxel en pacientes con cáncer de próstata castración sensibles en un centro oncológico nacional / Initial experience in safety, tolerance and adherence to the use of docetaxel in patients with sensitive castration prostate cancer in a national cancer center

INTRODUCCIÓN: El cáncer de próstata (PC) es una enfermedad de alta incidencia y prevalencia (90/100.00 habitantes) y constituye la segunda causa por muerte oncológica en hombres, fenómeno que acontece en su fase metastásica (mPC). El tratamiento estándar en esta etapa corresponde a la terapia de deprivación androgénica (TDA) que produce una respuesta oncológica favorable en términos de descenso del PSA y estabilización y/o regresión de las metástasis. Ésta primera etapa (castración sensible) dura en promedio 2 a 3 años, tras lo cual ocurre una independización tumoral del estímulo androgénico, fenómeno conocido como castración-resistencia (mCRPC). En esta etapa la quimioterapia (QMT) con docetaxel prolonga la sobrevida aproximadamente 4 meses, lo cual en conjunto con otros tratamientos de segunda línea (abiraterona, enzalutamida, etc.) logra alcanzar una sobrevida media desde el diagnostico de mCRPC de 24 meses. Diversos estudios (CHAARTED y STAMPEDE) han demostrado que el inicio de docetaxel junto con TDA en pacientes con mPC castración-sensible (mCSPC) prolongan sobrevida global hasta 17 meses, especialmente si hay alto volumen de enfermedad. El objetivo del estudio es describir las características clínicas, la respuesta oncológica inicial y el perfil de efectos adversos de pacientes con mCSPC sometidos a docetaxel. MATERIALES Y MÉTODOS: Estudio retrospectivo descriptivo entre mayo 2014 a Julio 2017. Se incluyeron pacientes ng/ml (rango 10,8 - 5550) y mediana de seguimiento 6 meses (rango 3 ­ 20). Catorce pacientes tenían Gleason > 8, 18 eran M+ de los cuales 9 eran viscerales. Solo uno recibió tratamiento local previo. La mediana de inicio de QMT fue 3,1 (0 ­ 6,1) meses post inicio TDA.Dieciséis pacientes completaron docetaxel y 4 siguen en curso. No hubo suspensión de QMT por efectos adversos. Los más frecuentes fueron diarrea (8/20), neuropatía (5/20) y vómitos (2/20). La mayoría fue grado 1 y solo tres presentaron complicaciones grado 3 (diarrea, leucopenia y trombocitopenia). No hubo complicaciones grado 4 -5. Diez pacientes alcanzaron un antígeno < 2 ng/ml a las 12 semanas post tratamiento y 7 presentaron recidiva bioquímica durante el seguimiento. Uno tuvo respuesta imagenológica completa, 10 respuesta parcial, 7 estabilidad y 2 mostraron progresión. CONCLUSIONES: El uso de Docetaxel en mCSPC es seguro, presenta escasos efectos adversos (la mayoría de intensidad leve) que no motivan suspensión. El tratamiento con docetaxel exhibe una respuesta prometedora en términos de control de PSA, sin embargo se requiere mayor seguimiento de esta cohorte para evaluar impacto en sobrevida. con mCSPC con enfermedad de alto volumen (metástasis óseas extra-axiales, viscerales o Gleason 9-10) y ECOG 0-1. Los pacientes recibieron TDA y seis ciclos de Docetaxel. Se registraron datos demográficos, clínicos, histopatológicos, PSA, imagenológicos (RECIST V1.1) y toxicidad (NCI CAE 4.0) RESULTADOS: Se incluyeron 20 pacientes, mediana de edad 63 años (rango 49 ­ 75). Mediana PSA de ingreso 267,5 ng/ml (rango 10,8 - 5550) y mediana de seguimiento 6 meses (rango 3 ­ 20). Catorce pacientes tenían Gleason > 8, 18 eran M+ de los cuales 9 eran viscerales. Solo uno recibió tratamiento local previo. La mediana de inicio de QMT fue 3,1 (0 ­ 6,1) meses post inicio TDA.Dieciséis pacientes completaron docetaxel y 4 siguen en curso. No hubo suspensión de QMT por efectos adversos. Los más frecuentes fueron diarrea (8/20), neuropatía (5/20) y vómitos (2/20). La mayoría fue grado 1 y solo tres presentaron complicaciones grado 3 (diarrea, leucopenia y trombocitopenia). No hubo complicaciones grado 4 -5. Diez pacientes alcanzaron un antígeno < 2 ng/ml a las 12 semanas post tratamiento y 7 presentaron recidiva bioquímica durante el seguimiento. Uno tuvo respuesta imagenológica completa, 10 respuesta parcial, 7 estabilidad y 2 mostraron progresión. CONCLUSIONES: El uso de Docetaxel en mCSPC es seguro, presenta escasos efectos adversos (la mayoría de intensidad leve) que no motivan suspensión. El tratamiento con docetaxel exhibe una respuesta prometedora en términos de control de PSA, sin embargo se requiere mayor seguimiento de esta cohorte para evaluar impacto en sobrevida.(AU)

INTRODUCTION: Prostate cancer is a disease with high incidence and prevalence (90/100.000 habitants) and the second cause of cancer related death in men. Standard treatment in this setting is androgen-deprivation therapy (TDA), which causes decrease in PSA levels and stabilization or regression of metastatic lesions. Responses in castration sensitive phase last in average 3 years, after which tumor is described to become independent from the androgenic stimuli, reaching a castration-resistance (mCRPC) state. At this point chemotherapy with docetaxel as well as second line treatments (abiraterone, enzalutamide, among others)have shown to improve survival in 4 months with mean survival from diagnosis of mCRPC of 24 months. Studies including CHAARTED and STAMPEDE have demonstrated that early treatment with docetaxel with ADT in patients with mCSPC prolongs overall survival, especially if high volume disease exists. This study describes the clinical characteristics, initial oncologic response and side effects profile of mCSPC treated with Docetaxel plus ADT. MATERIALS AND METHODS: Descriptive Retrospective study from May 2014 to July 2017. mCSPC patients with high volume disease (extra axial bone metastasis, visceral metastasis or Gleason 9-10) and ECOG 0-1 were included. Patients received ADT and 6 cycles of Docetaxel. Demographic, clinical and histopathological characteristicswere registered, together with PSA, radiologic data (RECIST V1.1) and toxicity (NCI CAE 4.0). RESULTS: 20 patients were included, median age 63 years (49-75 range). Median initial PSA 267,5 ng/ml (10,8-5550 range), and median follow up 6 months (3-20 range). Fourteen patients had Gleason > 8, 18presented bone metastasis and 9/14 viscerametastasis. Only 1 patient received previous local treatment. Median initialtime to initiation of Docetaxel post ADT was 3,1 (0-6,1) months.Sixteen patients completed docetaxel and 4 are still receiving treatment. There was no chemotherapy suspension due side effects. Most frequent side effects were diarrhea (8/20), neuropathy (5/20) and vomiting (2/20). Most were grade 1 and three patients presented grade 3 side effects (diarrhea, leukopenia and thrombocytopenia). No grade 4-5 side effects were reported.Ten patients reached PSA< 2 ng/m after 12 weeks of treatment, and 7 had biochemical relapse during follow up. One had complete radiologic response, 10 partial response, 7 remained stable and 2 showed progression of disease. CONCLUSION: The use of docetaxel in mCSPC isassociated to few side effects and none requiredsuspension of treatment. Treatment with Docetaxel exhibits promising results in terms of decrease in PSA, however longer follow up and greater number of patients are required to report benefits in overall survival.(AU)

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

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.

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.

[Massive pulmonary thromboembolism treated successfully with streptokinase. Report of one case]. / Tromboembolismo pulmonar masivo con respuesta exitosa a trombolisis farmacológica. Caso clínico.

Massive pulmonary thromboembolism has a high mortality. Early thrombolysis is the treatment of choice. We report a 79-year-old man admitted in shock. A chest angio-CAT scan showed a massive pulmonary thromboembolism. A transthoracic echocardiography showed a right cardiac dysfunction. Although the patient was in hemodynamic instability, he was subjected to thrombolysis with streptokinase, assisted with noradrenaline support and invasive mechanical ventilation. Parenteral anticoagulation was started thereafter. A second echocardiography, performed 72 hours later showed an improvement in right ventricular function. The patient had a nosocomial pneumonia that was treated. Noradrenalin and mechanical ventilation were discontinued nine and 15 days after thrombolysis. A new angio-CAT scan, 23 days after the procedure, was normal. The patient was discharged in good conditions 27 days after admission.

Tromboembolismo pulmonar masivo con respuesta exitosa a trombolisisfarmacológica: Caso clínico / Massive pulmonary thromboembolism treated successfully with streptokinase: Report of one case

Massive pulmonary thromboembolism has a high mortality. Early thrombolysis is the treatment of choice. We report a 79-year-old man admitted in shock. A chest angio-CAT scan showed a massive pulmonary thromboembolism. A transthoracic echocardiography showed a right cardiac dysfunction. Although the patient was in hemodynamic instability, he was subjected to thrombolysis with streptokinase, assisted with noradrenaline support and invasive mechanical ventilation. Parenteral anticoagulation was started thereafter. A second echocardiography, performed 72 hours later showed an improvement in right ventricular function. The patient had a nosocomial pneumonia that was treated. Noradrenalin and mechanical ventilation were discontinued nine and 15 days after thrombolysis. A new angio-CAT scan, 23 days after the procedure, was normal. The patient was discharged in good conditions 27 days after admission.

Severe novel H1N1 influenza A infection in the immediate postoperative period of a liver transplant patient.

In 2009, the World Health Organization recognized the novel H1N1 influenza A virus as a pandemic infection. Since April 2009, thousands of cases of novel H1N1 influenza A infection have been reported worldwide, and they have resulted in thousands of deaths. South American countries were affected by this infection during their winter season, and Chile presented one of the highest incidence rates. We have recently managed a liver transplant patient who presented with a severe novel H1N1 influenza A infection in the early postoperative period and required prolonged mechanical ventilation. The early suspicion of this infection during the current pandemic influenza in Chile made possible a timely treatment with oseltamivir. We decided to report this case because no other cases of liver transplant patients affected by H1N1 influenza A have been reported so far. We intend to alert clinicians about this potentially devastating viral infection in view of the current pandemic scenario, and here we review some of the recommendations for its prevention, diagnosis, therapy, and possible complications.

Púrpura trombocitopénico trombótico con respuesta exitosa a vincristina / Successful treatment of thrombotic thrombocytopenic purpura with vincristine report of one case

Thrombotic thrombocytopenic purpura presents as a multisystemic disease with thrombocytopenia, microangiopathic hemolytic anemia, fever, neurological and renal involvement. We report a 24 years-old male presenting with purpura and a generalized seizure. His blood tests showed an hemolytic anemia, unconjungated hyperbilirubinemia, increased lactated dehydrogenase, thrombocytopenia and impairment of renal function. He was initially treated with daily plasmapheresis and steroids without improvement. Due to persistence of the disease, he was treated with two doses of intravenous vincristine in four days, with clinical and laboratory improvement. He was discharged 40 days after the last dose of vincristine, in good conditions.

[Metachronic testicular tumor secondary to invasive bladder carcinoma]. / Tumor testicular metacronico secundario a carcinoma vesical infiltrante.

OBJECTIVE: To report a rare case of testicular metastasis secondary to an infiltrative transitional cell carcinoma years after radical surgery. CASE REPORT: 71-year-old male patient with history of infiltrative bladder tumor, status post radical cystoprostatectomy with urethrectomy. Seven years after surgery he presents with pain and swelling in the right testicle. Inguinal orchyectomy was carried out with the pathologic diagnosis of testicular metastasis of a high-grade transitional cell carcinoma. We perform a bibliographic review. RESULTS: The patient is disease-free twelve months after orchyectomy. CONCLUSIONS: Apart from leukemia and lymphoma, testicular metastases are extremely rare. The existence of testicular metastases means a metastatic dissemination to other organs, therefore chemotherapy could improve prognosis.

Tumor testicular metacrónico secundario a carcinoma vesical infiltrante / Metachronic testicular tumor secondary to invasive bladder carcinoma

OBJETIVOS: Presentar un caso raro de metástasis testicular secundaria a carcinoma urotelial infiltrante años después de practicada cirugía radical. METODOS: Exposición del caso clínico: paciente de 71 años sometido a cistoprostatectomía radical con uretrectomía por tumor vesical infiltrante. A los siete años debuta con dolor y aumento del tamaño testicular derecho. Se le practicó orquiectomía por vía inguinal siendo diagnosticado de metástasis testicular de carcinoma vesical de alto grado. y revisión de la literatura publicada al respecto. RESULTADOS: Supervivencia libre de enfermedad a los 12 meses de la orquiectomía. CONCLUSIONES: El tumor testicular metastático excluyendo leucemias y linfomas es extremadamente raro. La presencia de metástasis testiculares supone una diseminación metastásica a otros niveles y por ello la Quimioterapia podría mejorar el pronóstico (AU)

OBJECTIVE: To report a rare case of testicular metastasis secondary to an infiltrative transitional cell carcinoma years after radical surgery. METHODS: Case Report: 71-year-old male patient with history of infiltrative bladder tumor, status post radical cystoprostatectomy with urethrectomy. Seven years after surgery he presents with pain and swelling in the right testicle. Inguinal orchyectomy was carried out with the pathologic diagnosis of testicular metastasis of a high-grade transitional cell carcinoma. We perform a bibliographic review. RESULTS: The patient is disease-free twelve months after orchyectomy. CONCLUSIONS: Apart from leukemia and lymphoma, testicular metastases are extremely rare. The existence of testicular metastases means a metastatic dissemination to other organs, therefore chemotherapy could improve prognosis