Intravascular papillary endothelial hyperplasia (Masson tumor) mimicking a sarcoma and developing from an arteriovenous hemodialysis fistula.

Intravascular papillary endothelial hyperplasia (IPEH), also known as Masson's tumor, is a rare nonneoplastic vascular lesion caused by the abnormal proliferation of endothelial cells. Clinically and radiologically, IPEH presents as a soft tissue mass that may simulate and be mistaken for a sarcomatous tumor. There have been reports of this entity involving the skin or subcutaneous tissues in normal blood vessels and vascular malformations. Herein, we present the first reported case of Masson's tumor arising from an arteriovenous hemodialysis fistula. We emphasize the imaging features of this lesion and briefly discuss its pathophysiology.

Brain metastases from lung cancer responding to erlotinib: the importance of EGFR mutation.

Median survival of patients with brain metastases from nonsmall cell lung cancer (NSCLC) is poor and more effective treatments are urgently needed. We have evaluated the efficacy of erlotinib in this setting and its association with activating mutations in the epidermal growth factor receptor (EGFR) gene. We retrospectively identified patients with NSCLC and brain metastases treated with erlotinib. EGFR mutations in exons 19 and 21 were analysed by direct sequencing. Efficacy and tolerability were compared according to EGFR mutational status. 69 NSCLC patients with brain metastases were identified, 17 of whom harboured EGFR mutations. Objective response rate in patients with EGFR mutations was 82.4%; no responses were observed in unselected patients (p<0.001). Median (95% CI) time to progression within the brain for patients harbouring EGFR mutations was 11.7 (7.9-15.5) months, compared to 5.8 (5.2-6.4) months for control patients whose EGFR mutational status had not been assessed (p<0.05). Overall survival was 12.9 (6.2-19.7) months and 3.1 (2.5-3.9) months (p<0.001), respectively. The toxicity of erlotinib was as expected and no differences between cohorts were observed. Erlotinib is active in brain metastases from NSCLC; this clinical benefit is related to the presence of activating mutations in exons 19 or 21 of the EGFR gene.

Endobronchial ultrasound-guided transbronchial needle aspiration for identifying EGFR mutations.

The presence of somatic mutations of the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) gene in patients with advanced nonsmall cell lung cancer (NSCLC) correlates with a good response to tyrosine kinase inhibitors. The usefulness of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for the detection of EGFR mutations in cells recovered from malignant mediastinal nodes in patients with NSCLC was assessed. All patients with lung adenocarcinoma or unspecified NSCLC referred for staging with EBUS-TBNA were included. Nodes with a short-axis diameter of >5 mm were sampled, and genomic DNA from metastatic tumour cells was obtained for analysis of exons 19 and 21. The impact of sampling on management was assessed. EGFR gene analysis of the EBUS-TBNA sample was feasible in 26 (72.2%) out of the 36 patients with lymph node metastasis. Somatic mutations of the EGFR gene were detected in tissue obtained through EBUS-TBNA in two (10%) out of 20 patients with metastasic lung adenocarcinoma. Malignant tissue samples obtained by EBUS-TBNA from patients with nodal metastasis of NSCLC are suitable for the detection of EGFR mutations in most cases, and this technique demonstrates mutated neoplastic cells in a tenth of patients with adenocarcinoma.

Polymorphisms in DNA repair genes modulate survival in cisplatin/gemcitabine-treated non-small-cell lung cancer patients.

BACKGROUND: Impaired DNA repair capacity may favorably affect survival in cisplatin/gemcitabine-treated non-small-cell lung cancer (NSCLC) patients. We investigated the association of survival with genetic polymorphisms in X-ray repair cross-complementing group 1 and group 3 (XRCC3), xeroderma pigmentosum group D (XPD), excision repair cross-complementing group 1, ligase IV, ribonucleotide reductase, TP53, cyclooxygenase-2, interleukin-6, peroxisome proliferator-activated receptor gamma, epidermal growth factor, methylene-tetra-hydrofolate reductase and methionine synthase. PATIENTS AND METHODS: One hundred and thirty-five stage IV or IIIB (with malignant pleural effusion) NSCLC patients treated with cisplatin/gemcitabine from different hospitals of the Spanish Lung Cancer Group were genotyped for 14 different polymorphisms in 13 genes. Polymorphisms were detected by the TaqMan method, using genomic DNA extracted from baseline blood samples. RESULTS: Median survival was significantly increased in patients harboring XRCC3 241 MetMet: 16 months versus 10 months for patients with ThrMet and 14 months for those with ThrThr (P = 0.01). The risk of death ratio was significantly lower for MetMet than for ThrMet patients (hazard ratio, 0.43; P = 0.01). In the multivariate Cox model, XRCC3 241 remained an independent prognostic factor (hazard ratio: XRCC3 241 MetMet, 0.44; P = 0.01), and XPD 751 and XRCC1 399 also emerged as significant prognostic factors (hazard ratios: XPD 751 LysGln, 0.46, P = 0.03; XRCC1 399 ArgGln, 0.61, P = 0.04). No other association was observed between genotype and survival. CONCLUSION: XRCC3 241 MetMet is an independent determinant of favorable survival in NSCLC patients treated with cisplatin/gemcitabine. A simple molecular assay to determine the XRCC3 241 genotype can be useful for customizing chemotherapy.

Epidermal growth factor receptor activating mutations in Spanish gefitinib-treated non-small-cell lung cancer patients.

BACKGROUND: North American and Japanese non-small-cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) activation via tyrosine kinase (TK) mutations respond dramatically to gefitinib treatment. To date, however, the frequency and effect of EGFR TK mutations have not been examined in European patients. PATIENTS AND METHODS: Eighty-three Spanish advanced NSCLC patients who had progressed after chemotherapy, were treated with compassionate use of gefitinib. Patients were selected on the basis of available tumor tissue. Tumor genomic DNA was retrieved from paraffin-embedded tissue obtained by laser capture microdissection. EGFR mutations in exons 19 and 21 were examined by direct sequencing. RESULTS: EGFR mutations were found in 10 of 83 (12%) of patients. All mutations were found in adenocarcinomas, more frequently in females (P=0.007) and non-smokers (P=0.01). Response was observed in 60% of patients with mutations and 8.8% of patients with wild-type EGFR (P=0.001). Time to progression for patients with mutations was 12.3 months, compared with 3.6 months for patients with wild-type EGFR (P=0.002). Median survival was 13 months for patients with mutations and 4.9 months for those with wild-type EGFR (P=0.02). CONCLUSIONS: EGFR TK mutational analysis is a novel predictive test for selecting lung adenocarcinoma patients for targeted therapy with EGFR TK inhibitors.

Tissue production of pro-inflammatory cytokines (IL-1beta, TNFalpha and IL-6) correlates with the intensity of the systemic inflammatory response and with corticosteroid requirements in giant-cell arteritis.

OBJECTIVES: To investigate proinflammatory cytokine expression in temporal arteries from patients with giant-cell arteritis (GCA) and to analyse its relationship with the intensity of the initial systemic inflammatory reaction and response to corticosteroid therapy. METHODS: Quantification of interleukin-1beta (IL-1beta), tumor necrosis factor alpha (TNFalpha), and interleukin-6 (IL-6) mRNA by real-time quantitative PCR in temporal artery samples from 36 patients with biopsy-proven GCA and 11 controls. Immunohistochemical detection of IL-1beta, TNFalpha, and IL-6 in temporal artery sections from 74 patients with GCA and 15 controls. Clinical and biochemical parameters of inflammation as well as the time (weeks) required to reach a maintenance prednisone dose <10 mg/day were recorded. RESULTS: IL-1beta (13.8 +/- 2.5 vs 5.4 +/- 1.3 relative units, P = 0.012) and IL-6 transcripts (34 +/- 13.7 vs 7.8 +/- 4.5 relative units, P = 0.034) were significantly more abundant in patients with a strong systemic inflammatory response compared with those with no inflammatory parameters. Immunohistochemical scores for IL-1beta (2.7 +/- 0.3 vs 1.9 +/- 0.2, P = 0.018), TNFalpha (3.2 +/- 0.2 vs 2.4 +/- 0.3, P = 0.028) and IL-6 (3 +/- 0.2 vs 2.1 +/- 0.3, P = 0.023) were also significantly higher in patients with strong systemic inflammatory reaction. A significant correlation was found between the amount of tissue TNFalpha mRNA and the time required to reach a maintenance dose of prednisone <10 mg/day (r = 0.586, P = 0.001). CONCLUSION: GCA patients with a strong systemic inflammatory response, who have been previously shown to be more resistant to corticosteroid therapy, have elevated tissue expression of proinflammatory cytokines IL-1beta, TNFalpha and IL-6. High production of TNFalpha is associated with longer corticosteroid requirements.

Serum DNA as a tool for cancer patient management.

PURPOSE: Genetic analysis has shown that cell-free circulating DNA in plasma or serum of cancer patients shares similar genetic alterations to those described in the corresponding tumor. One of the most important alterations involved in carcinogenesis is aberrant promoter methylation. The interest in this field has grown due to the implementation of the methylation-specific PCR (MSP) assay. The main objective of this study is to analyze the methylation status of different genes in tumor and serum DNA obtained at the time of surgery in two different tumor models (glioblastoma [GBM] and non-small-cell lung cancer [NSCLC]) and their relationship to clinico-pathological characteristics and response to chemotherapy. MATERIAL AND METHODS: Using MSP assay, we assessed the methylation status of MGMT, RASSF1A, p16, DAPK, TMS-1 in tumor and serum DNA obtained at time of surgery or stereotactic biopsy from 28 GBM patients and from 51 NSCLC patients. RESULTS: In GBM patients, the prevalence of MGMT, p16, DAPK, and RASSF1A promoter methylation was 38.1%, 66.7%, 52.4%, 57.1%, respectively, in glioma tissue, and 39.3%, 53.6%, 34.3%, 50%, respectively, in serum. A high correlation between methylation in tumor and serum (Spearman test p = 0.0001) was observed. In NSCLC patients, RASSF1A, DAPK and TMS-1 were methylated in 34%, 45% and 35% tumors, respectively, and in 34%, 40% and 34% serum, respectively. A good correlation was found between alterations found in tumor and serum (Spearman test p = 0.0001). CONCLUSIONS: The study of serum or plasma DNA has opened new roads for translational research and new strategies for molecular diagnosis. Due to the similarities of alterations found in serum DNA and primary tumor, we can use this tool to calculate the risk of local or distant recurrence and its relationship with survival and its value in patient follow-up to evaluate response to therapy.

Dolor lumbar, fiebre, lesiones cutáneas e insuficiencia renal de curso rápidamente progresivo en una mujer de 44 años con antecedentes de trombosis arteriales y venosas de repetición / Lumbar pain, cutaneous lesions and renal failure with a progressive and rapid evolution in 44-year-old woman with a history of recurrent arterial and venous thrombosis

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[Detection of bacteremia in patients discharged from an emergency unit: study of 61 cases]. / Detección de bacteriemia en los pacientes dados de alta en urgencias: estudio de 61 episodios.

BACKGROUND: To know the prevalence, the clinical and microbiological characteristics of bacteremia episodes detected on discharged patients at the emergency unit, as well as the accordance of diagnostics and the predicting factors. PATIENTS AND METHODS: We analysed the cases with bacteria detected on discharged patients during 2 years (1995-1996) in an university hospital. We reported: age, sex isolated organism in blood cultures, bacteremia source, leukocytes count, presence of underlying conditions, and accordance between initial and final diagnosis. We compared the characteristics of the groups with bacteremia without apparent origin and the ones with evident clinical source. RESULTS: We detected 61 cases, the mean age was 55 years (SD = 21), and 54% were males. The most commonly isolated agent was E. coli (50%). The leukocytes count was higher 10 x 10(9)/l in 15%. The source of bacteremia was: urinary tract infection (54%) no clinical focus (31%), respiratory tract (11%) and biliary duct (3%). The 90% of urinary tract and the 71% of respiratory infections were correctly diagnosed. However only the 5% of bacteremias without apparent source was correctly diagnosed. We found these differences statistically a significant (p < 0.001 and p = 0.002). Underlying conditions were detected in the 84% of cases in bacteremia without apparently source: AIDS (22%), cirrhosis (22%), parenteral drugs addiction (17%) and venous catheter (17%). Comparing both groups, with apparent focus and without it, we found that the presence of underlying condition is the only independent factor which predispose to bacteremia (p = 0.000; RR = 4.6; IC 95% = 1.9-11.8). CONCLUSIONS: The prevalence of bacteremia detected in discharged patients at the emergency unit seems acceptable. However those results suggest that we could decrease the number of patients with bacteremia without apparently source, because this group shows up to be the less successful in diagnosis. In patients with fever and no clinical focus in the emergency unit, it is useful to consider the presence of underlying factors to decide its management.

Local anesthesia by jet-injection device in minor dermatologic surgery.

BACKGROUND: Pain and needle-phobia can be a problem during the application of local anesthesia with syringe and needle. OBJECTIVE: To evaluate a jet-injection device (without needle) to deliver local anesthesia. METHODS: Two hundred and six minor dermatological procedures using a jet-injection device for administering local anesthesia into skin tissue were performed. We comment on the technical procedures, application, usefulness in relation to areas involved and the anatomical location of lesion, and total dosage of the anesthetic agent. RESULTS: Total absence of pain during installation of anesthetic (N = 194; 94%). Good level of anesthesia in all patients. No local adverse effects. CONCLUSION: The jet-injection device is easy to handle, it is harmless, it provides good levels of anesthesia, and the dosage of anesthetic agent is smaller than the dosage administered with conventional methods.

[Changes in nutritional and biochemical parameters in septic patients undergoing total parenteral nutrition. Their relationship with mortality]. / Evolución de parámetros nutricionales y bioquímicos en pacientes sépticos bajo NPT. Su relación con la mortalidad.

The response of 24 septic patients admitted into the ICU to total parenteral nutrition was studied, and the course of the parameters evaluated from non-surviving (14) and surviving patients was compared. Serum glucose, triglyceride, albumin, transferrin, prealbumin, RBP, zinc levels and CD4/CD8 ratio were measured at 48 hours, 4 days and 8 days after the onset of parenteral nutrition. Overall, a significant increase in prealbumin (p less than 0.01) and RBP (p less than 0.05) levels were the only findings to parenteral nutrition response. When the non-surviving and surviving groups were compared, the former showed a significant increase in serum triglyceride (p less than 0.001), while a significant increase in serum transferrin and CD4/CD8 ratio (p less than 0.01) was observed in the latter.