Combined assessment of EGFR pathway-related molecular markers and prognosis of NSCLC patients

The purpose of this study is to evaluate the prognostic value of the combined assessment of multiple molecular markers related to the epidermal growth factor receptor (EGFR) pathway in resected non-small cell lung cancer (NSCLC) patients. Tumour specimens of 178 NSCLC patients were collected and analysed for EGFR and KRAS mutation status by DNA sequencing, and for EGFR copy number by fluorescent in situ hybridisation. Tissue microarrays were generated and used to determine the expression of multiple EGFR pathway-related proteins by immunohistochemistry. We analysed the association between each marker and patient prognosis. Univariate analyses for each clinical variable and each molecular marker were performed using Kaplan–Meier curves and log-rank tests. From these results, we selected the variables KRAS mutations and expression of cytoplasmic EGFR, granular pERK, nuclear pSTAT3, cytoplasmic E-cadherin and cytoplasmic pCMET to enter into a Cox proportional hazards model, along with stage as the strongest clinical variable related with prognosis. Of the EGFR-related markers evaluated here, the markers EGFR, pERK, pSTAT3, E-cadherin, pCMET and mutations in KRAS were associated with survival when analysed in combination in our patient cohort, with P=0.00015 as the P-value for a test of the additional impact of markers on prognosis, after taking stage into consideration. Confirmation of the impact of these markers in independent studies will be necessary.     

Müllerian adenosarcoma of the cervix with heterologous elements: report of a case and review of the literature.

BACKGROUND: Müllerian adenosarcoma (MA) is a rare neoplasm composed of benign epithelial and malignant stromal components. Its location in the cervix and the presence of heterologous elements are extremely infrequent (to our knowledge, only 14 more cases have been reported in the English literature). We describe another case of MA of the uterine cervix with heterologous elements and review the clinical and pathological features of these tumors. CASE REPORT: A nulliparous 25-year-old woman was admitted to the hospital because of metrorrhagia and recurrent masses, dependent on the cervix, initially considered endocervical polyps. Microscopically, the last curettage performed revealed a tumor composed of two elements, epithelial and mesenchymal. The epithelial elements were benign endocervical type glands, and the mesenchymal were sarcomatous, containing minor foci of cartilage. A diagnosis of endocervical heterologous adenosarcoma was reached, and a total hysterectomy and bilateral salpingo-oophorectomy were performed. The patient is alive 2 years after the surgical procedure. Neither chemotherapy nor other adjuvant therapies have been administered, and she is clinically free of disease at the moment. CONCLUSION: Because MA with heterologous elements seems to appear at the earliest stages of the reproductive lifespan in women, commonly with a history of recurrent polyps, and because its malignant potential is uncertain, gynecologists and pathologists should be aware and think about the possibility of this tumor. Long-term follow-up is essential and so is the accumulation of individual cases to provide further experience with these unusual neoplasms.     

KRAS mutations predict progression of preneoplastic gastric lesions.

Eight hundred sixty-three subjects with atrophic gastritis were recruited to participate in an ongoing chemoprevention trial in Nari?o, Colombia. The participants were randomly assigned to intervention therapies, which included treatment to eradicate Helicobacter pylori infection followed by daily dietary supplementation with antioxidant micronutrients in a 2 x 2 x 2 factorial design. A series of biopsies of gastric mucosa were obtained according to a specified protocol from designated locations in the stomach for each participant at baseline (before intervention therapy) and at year three. A systematic sample of 160 participants was selected from each of the eight treatment combinations. DNA was isolated from each of these biopsies (n = 320), and the first exon of KRAS was amplified using PCR. Mutations in the KRAS gene were detected using denaturing gradient gel electrophoresis and confirmed by sequence analysis. Of all baseline biopsies, 14.4% (23 of 160) contained KRAS mutations. Among those participants with atrophic gastritis without metaplasia, 19.4% (6 of 25) contained KRAS mutations, indicating that mutation of this important gene is likely an early event in the etiology of gastric carcinoma. An important association was found between the presence of KRAS mutations in baseline biopsies and the progression of preneoplastic lesions. Only 14.6% (20 of 137) of participants without baseline KRAS mutations progressed from atrophic gastritis to intestinal metaplasia or from small intestinal metaplasia to colonic metaplasia; however, 39.1% (9 of 23) with baseline KRAS mutations progressed to a more advanced lesion after 3 years [univariate odds ratio (OR), 3.76 (P = 0.05); multivariate OR adjusted for treatment, 3.74 (P = 0.04)]. In addition, the specificity of the KRAS mutation predicted progression. For those participants with G-->T transversions at position 1 of codon 12 (GGT-->TGT), 19.4% (5 of 17) progressed (univariate OR, 2.4); however, 60.0% (3 of 5) of participants with G-->A transitions at position 1 of codon 12 (GGT-->AGT) progressed (univariate OR, 8.7; P = 0.004 using chi2 test).     

Drug-related hepatotoxicity and hepatic failure following combined androgen blockade

Androgen deprivation therapy has been the mainstay of treatment for metastatic prostate cancer and of less advanced cancers as neoadjuvant and adjuvant treatment. Abnormal liver function test, in particular elevated transaminases, is an adverse reaction more frequently noticed during androgen deprivation therapy with antiandrogen. We report the case of a patient with acute hepatic failure associated with the use of bicalutamide.     

Hematomas renales tras Litotricia Extracorpórea por Ondas de Choque (LEOCH)

IntroductionThe use of fragmentation due to shock- waves as a treatment of urinary stone was one of the most important therapeutics findings in the history of urology. It´s the first election treatment for most of the calculus at renal and urethral location due to the fact that it is a low invasive treatment and it has a few number of complications, but this method also has a few negative side effects, it can caused a more or less important traumatic lesion at the organs which crosses the shock- waves, including the kidney where it can caused a small contusion or renal hematoma with different resolution and treatment.Material and methodWe reviewed 4815 extracorporeal shock-wave lithotripsy that we performed in our department in which we found six cases with subcapsular and perirrenal hematoma which we followed up and treated.ResultsAfter the urological complications (pain, obstruction and infection) the renal and perirrenal hematic collections are the most frequent adverse effects of shock- waves used in lithotripsy, these are related to the power of energy used and patient age.ConclusionsBetween the years 1992-2007 we performed 4.815 extracorporeal shock-wave lithotripsy finding seven cases of severe hematoma, less then 1%.Treatment of these complications is usually not aggressive though sometimes it is necessary to perform surgical drainage and even nephrectomy.     

Banff Schema for Grading Pancreas Allograft Rejection: Working Proposal by a Multi-Disciplinary International Consensus Panel

Accurate diagnosis and grading of rejection and other pathological processes are of paramount importance to guide therapeutic interventions in patients with pancreas allograft dysfunction. A multi-disciplinary panel of pathologists, surgeons and nephrologists was convened for the purpose of developing a consensus document delineating the histopathological features for diagnosis and grading of rejection in pancreas transplant biopsies. Based on the available published data and the collective experience, criteria for the diagnosis of acute cell-mediated allograft rejection (ACMR) were established. Three severity grades (I/mild, II/moderate and III/severe) were defined based on lesions known to be more or less responsive to treatment and associated with better- or worse-graft outcomes, respectively. The features of chronic rejection/graft sclerosis were reassessed, and three histological stages were established. Tentative criteria for the diagnosis of antibody-mediated rejection were also characterized, in anticipation of future studies that ought to provide more information on this process. Criteria for needle core biopsy adequacy and guidelines for pathology reporting were also defined.
The availability of a simple, reproducible, clinically relevant and internationally accepted schema for grading rejection should improve the level of diagnostic accuracy and facilitate communication between all parties involved in the care of pancreas transplant recipients.     

A Dietitian-Delivered Group Nutrition Program Leads to Reductions in Dietary Fat, Serum Cholesterol, and Body Weight: The Worcester Area Trial for Counseling in Hyperlipidemia (WATCH)

OBJECTIVE: To assess the effectiveness of a dietitian-based nutrition counseling and education program for patients with hyperlipidemia. DESIGN: A 4-session program implemented as a complement to a randomized physician-delivered intervention. SUBJECTS/SETTING: From 12 practice sites of the Fallon Clinic, 1,162 subjects with hyperlipidemia were recruited, 645 of whom had data sufficient for our primary analyses. INTERVENTION: Two individual and 2 group sessions conducted over 6 weeks. MAIN OUTCOME MEASURES: Total and saturated fat levels; serum low-density lipoprotein cholesterol levels; and body weight, measured at baseline and after 1 year. STATISTICAL ANALYSES: Multiple linear regression was used to evaluate changes in outcome measures. RESULTS: After 1 year, there were significant reductions in outcome measures for subjects attending 3 or 4 nutrition sessions vs subjects attending fewer than 3 sessions or those never referred to a nutrition session. Reductions (mean +/- standard error) in saturated fat (measured as percent of energy) were 2.7 +/- 0.5%, 2.1 +/- 0.5%, and 0.3 +/- 0.1%, respectively. These reductions correspond to roughly a 22% relative change from baseline in those attending 3 or 4 sessions. Corollary reductions were observed for total fat (measured as percent of energy): 8.2 +/- 1.4%, 5.0 +/- 1.4%, and 0.7 +/- 0.4%; low-density lipoprotein cholesterol: 0.48 +/- 0.11 mmol/L, 0.13 +/- 0.11 mmol/L, and 0.02 +/- 0.03 mmol/L; and body weight: 4.5 +/- 0.9 kg, 2.1 +/- 0.8 kg, and 1.1 +/- 0.2 kg. The specified changes were additive to those of the physician-delivered intervention. APPLICATIONS/CONCLUSIONS: This investigation provides empirical data demonstrating the effectiveness of a dietitian-delivered intervention in the care of patients with hyperlipidemia.     

Does focal destruction of the thoracic aorta wall by Staphylococcus aureus lead to the development of infected aneurysms? An experimental study.

Objective: The infrequency of infected aneurysms suggests that either infection of segments of the aortic wall is uncommon, or that infections do not always lead top infected aneurysm formation. The purpose of the study was to determine whether focal Staphylococcus aureus infection of aortic wall segments leads consistently to the development of infected aneurysms and to evaluate the segments in which infection did not lead to the infected aneurysm formation. Methods: Twenty pigs were inoculated with 0.1 ml of a Staphylococcus aureus inoculum in three segments of the thoracic aorta wall (study group). In another 10 pigs, 0.1 ml of saline solution was injected in three segments of the thoracic aorta wall (control group). Study group: histological abnormalities and bacterial culture of the inoculation sites were evaluated at 10 days (n=5 pigs), 30 days (n=5 pigs), and 90 days (n=10 pigs). Control group: histological abnormalities were evaluated at 10 days (n=5 pigs) and 90 days (n=5 pigs). Results: Study group: infected aneurysms developed in only two animals killed at 30 days. At 90 days, destruction of the elastic tissue, scar tissue and neointima formation were found in all the aortic segments studied. Control group: no significant changes were found in any of the segments evaluated. Conclusion: In our experimental model, acute local infection by S. aureus caused the development of infected aortic aneurysm in only 10% of the animals. In the remaining 90%, healing of the site of infection followed resolution of the infection.