Perioperative Treatment of Gastrointestinal Stromal Tumors

This review describes the current multidisciplinary management of gastrointestinal stromal tumor (GIST), which is the most common sarcoma of the gastrointestinal tract. Before 2001, surgery was the only effective therapy for GIST. The discovery of the central role of KIT proto-oncogene mutations in the pathogenesis of this tumor, and the development of specific inhibitors of KIT tyrosine kinase (TK) function, has changed the paradigm of treatment for GISTs. Imatinib and sunitinib are TK inhibitors with activity against GISTs. Their major established role in GIST is in the treatment of advanced disease. A growing body of literature and clinical experience support the potential perioperative use of these drugs. The adjuvant use of imatinib is based on retrospective series and limited prospective studies demonstrating that imatinib reduces the risk of recurrence. Ongoing studies are further defining the length of adjuvant therapy, as well as identifying the patients that could achieve the best results. Neoadjuvant treatment often decreases the tumor size, allowing a less morbid surgery, appears to be safe and beneficial for some patients, and therefore deserves further study.

Asthma mortality in Australia 1920-94: Age, period, and cohort effects

Study objective-To investigate asthma mortality during 1920-94 in Australia in order to assess the relative role of period and birth cohort effects. Design-Asthma mortality (both sexes) was age standardised and examined for changes over time. The data were also examined for age, period, and cohort (APC) effects using Poisson regression modelling. Setting-National Australian mortality data. Participants-Population (both sexes) aged 15-34 years, 1920-94. Main results-Age adjusted period rates indicate an increase in asthma mortality during the 1950s, and increases and subsequent falls (epidemics) during the mid 1960s and late 1980s. APC modelling suggested an increasing cohort effect (adjusted for both age and period) from the birth cohort 1950-54 onwards. Period effects (adjusted for age and cohort) are characterised by an increase in the 1950s (possibly due to changes in diagnostic labelling), minimal or no increases in the mid 1960s and late 1980s (where period peaks had been noted when data were adjusted for age only), and declines in mortality risk subsequent to the periods where age-period analysis had noted increases. Thus, in Australia, some of the mid 1960s epidemic in asthma deaths, and all of the late 1980s mortality increase, seem to be attributable to cohort effects. Conclusions-The increase in asthma mortality cohort effect is consistent with empirical evidence of recent increases in prevalence (and presumably incidence) of asthma in Australia, and suggests the need for more research into the underlying environmental aetiology of this condition.

Factors associated with mortality in patients with bloodstream infection and pneumonia due to Stenotrophomonas maltophilia

Severe infections caused by Stenotrophomonas maltophilia are associated with high mortality, and strategies to improve the clinical outcome for infected patients are needed. A retrospective cohort study of patients with bloodstream infection (BSIs) and pneumonia caused by S. maltophilia was conducted. Multivariate analysis was performed to access factors associated with 14-day mortality. A total of 60 infections were identified. Among these, eight (13%) were pneumonias and 52 were BSIs; 33.3% were primary, 13% were central venous catheter (CVC)-related and 40% were secondary BSIs. Fifty-seven (85%) patients had received previous antimicrobial therapy; 88% had CVC, 57% mechanical ventilation and 75% were in the intensive care unit at the onset of infection. Malignancy (45%) was the most frequent underlying disease. The mean of the Acute Physiology and Chronic Health Evaluation II (APACHE II) scores was 17 and for the Sepsis-related Organ Failure Assessment (SOFA) score, it was 7 points. The overall and 14-day mortality were, respectively, 75% and 48%. Forty-seven (78%) patients were treated and, of these, 74% received trimethoprim-sulfamethoxazole. Independent risk factors associated with mortality were SOFA index > 6 points (0.005) and septic shock (0.03). The Kaplan-Meier estimations curves showed that patients with APACHE II score > 20 and SOFA score > 10 had a survival chance of, respectively, less than 8% and less than 10% (P <= 0.001) at 21 days after the first positive S. maltophilia culture. Our results suggest that the independent factors associated with outcome in patients with infection caused by S. maltophilia are septic shock and higher SOFA index.

Early neonatal morbidity and mortality in growth-discordant twins

Objective. To evaluate early neonatal morbidity and mortality in twin pregnancies with growth discordance. Design. Retrospective study. Setting. Tertiary teaching hospital, Sao Paulo, Brazil. Population. A total of 151 twin pregnancies managed and delivered at the Multiple Pregnancy Unit at Sao Paulo University Hospital between 1998 and 2004. Methods. Comparison between twin pregnancies with weight discordance 20% and pregnancies concordant for fetal weight. Cases with fetal death, abnormalities, twin-to-twin transfusion and delivery before 26 weeks or in another hospital were excluded. Outcome measures. Early neonatal morbidity (Apgar at 5 minutes 7, respiratory or neurological complications, infection, necrotizing enterocolitis, length of hospital stay) and mortality. Results. Forty (26.5%) pregnancies presented discordance 20% and 111 (73.5%) were concordant. In the discordant group, 75% of pregnancies had at least one growth restricted fetus (10th centile). In concordant twin pregnancies, monochorionic cases (22.5%) presented with lower gestational age (34.3 vs. 36.2 weeks), lower birthweight (2,067 vs. 2,334 g) and a longer period of hospital stay (5.5 vs. 3.0) compared to dichorionic concordant twins. No differences between monochorionic and dichorionic subgroups were observed in discordant twins. Pregnancies in which at least one baby was born with a birthweight below the 10th centile showed that discordant pregnancies had a lower gestational age at delivery (35.2 vs. 36.8 weeks) and a longer period of hospital stay (9 vs. 4 weeks) compared to concordant cases. Neonatal mortality was similar in discordant (3.7%) and concordant (4.5%) twins. Conclusion. Early perinatal morbidity is increased in twin pregnancies with birthweight discordance 20% only when associated with fetal growth restriction and low birthweight.

Trends in stroke incidence, mortality and case fatality rates in Joinville, Brazil: 1995-2006

Background: Studying stroke rates in a whole community is a rational way to assess the quality of patient care and primary prevention. However, there are few studies of trends in stroke rates worldwide and none in Brazil. Objective: Established study methods were used to define the rates for first ever stroke in a defined population in Brazil compared with similar data obtained and published in 1995. Methods: All stroke cases occurring in the city of Joinville during 2005-2006 were prospectively ascertained. Crude incidence and mortality rates were determined, and age adjusted rates and 30 day case fatality were calculated and compared with the 1995 data. Results: Of the 1323 stroke cases registered, 759 were first ever strokes. The incidence rate per 100 000 was 105.4 (95% CI 98.0 to 113.2), mortality rate was 23.9 (95% CI 20.4 to 27.8) and the 30 day case fatality was 19.1%. Compared with the 1995 data, we found that the incidence had decreased by 27%, mortality decreased by 37% and the 30 day case fatality decreased by 28%. Conclusions: Using defined criteria we showed that in an industrial southern Brazilian city, stroke rates are similar to those from developed countries. A significant decrease in stroke rates over the past decade was also found, suggesting an improvement in primary prevention and inpatient care of stroke patients in Joinville.

Air Pollution and Mortality in Latin America The Role of Education

Background: People with less education in Europe, Asia, and the United States are at higher risk of mortality associated with daily and longer-term air pollution exposure. We examined whether educational level modified associations between mortality and ambient particulate pollution (PM(10)) in Latin America, using several timescales. Methods: The study population included people who died during 1998-2002 in Mexico City, Mexico; Santiago, Chile; and Sao Paulo, Brazil. We fit city-specific robust Poisson regressions to daily deaths for nonexternal-cause mortality, and then stratified by age, sex, and educational attainment among adults older than age 21 years (none, some primary, some secondary, and high school degree or more). Predictor variables included a natural spline for temporal trend, linear PM(10) and apparent temperature at matching lags, and day-of-week indicators. We evaluated PM(10) for lags 0 and I day, and fit an unconstrained distributed lag model for cumulative 6-day effects. Results: The effects of a 10-mu g/m(3) increment in lag 1 PM(10) on all nonextemal-cause adult mortality were for Mexico City 0.39% (95% confidence interval = 0.131/-0.65%); Sao Paulo 1.04% (0.71%-1.38%); and for Santiago 0.61% (0.40%-0.83%. We found cumulative 6-day effects for adult mortality in Santiago (0.86% [0.48%-1.23%]) and Sao Paulo (1.38% [0.85%-1.91%]), but no consistent gradients by educational status. Conclusions: PM(10) had important short- and intermediate-term effects on mortality in these Latin American cities, but associations did not differ consistently by educational level.

International study of temperature, heat and urban mortality: the `ISOTHURM` project

Background This study describes heat- and cold-related mortality in 12 urban populations in low- and middle-income countries, thereby extending knowledge of how diverse populations, in non-OECD countries, respond to temperature extremes. Methods The cities were: Delhi, Monterrey, Mexico City, Chiang Mai, Bangkok, Salvador, So Paulo, Santiago, Cape Town, Ljubljana, Bucharest and Sofia. For each city, daily mortality was examined in relation to ambient temperature using autoregressive Poisson models (2- to 5-year series) adjusted for season, relative humidity, air pollution, day of week and public holidays. Results Most cities showed a U-shaped temperature-mortality relationship, with clear evidence of increasing death rates at colder temperatures in all cities except Ljubljana, Salvador and Delhi and with increasing heat in all cities except Chiang Mai and Cape Town. Estimates of the temperature threshold below which cold-related mortality began to increase ranged from 15 degrees C to 29 degrees C; the threshold for heat-related deaths ranged from 16 degrees C to 31C. Heat thresholds were generally higher in cities with warmer climates, while cold thresholds were unrelated to climate. Conclusions Urban populations, in diverse geographic settings, experience increases in mortality due to both high and low temperatures. The effects of heat and cold vary depending on climate and non-climate factors such as the population disease profile and age structure. Although such populations will undergo some adaptation to increasing temperatures, many are likely to have substantial vulnerability to climate change. Additional research is needed to elucidate vulnerability within populations.

Vulnerability to heat-related mortality in Latin America: A case-crossover study in Sao Paulo, Brazil, Santiago, Chile and Mexico City, Mexico

Background Factors affecting vulnerability to heat-related mortality are not well understood. Identifying susceptible populations is of particular importance given anticipated rising temperatures from climatic change. Methods We investigated heat-related mortality for three Latin American cities (Mexico City, Mexico; Sao Paulo, Brazil; Santiago, Chile) using a case-crossover approach for 754 291 deaths from 1998 to 2002. We considered lagged exposures, confounding by air pollution, cause of death and susceptibilities by educational attainment, age and sex. Results Same and previous day apparent temperature were most strongly associated with mortality risk. Effect estimates remained positive though lowered after adjustment for ozone or PM(10). Susceptibility increased with age in all cities. The increase in mortality risk for those >= 65 comparing the 95th and 75th percentiles of same-day apparent temperature was 2.69% (95% CI: -2.06 to 7.88%) for Santiago, 6.51% (95% CI: 3.57-9.52%) for Sao Paulo and 3.22% (95% CI: 0.93-5.57%) for Mexico City. Patterns of vulnerability by education and sex differed across communities. Effect estimates were higher for women than men in Mexico City, and higher for men elsewhere, although results by sex were not appreciably different for any city. In Sao Paulo, those with less education were more susceptible, whereas no distinct patterns by education were observed in the other cities. Conclusions Elevated temperatures are associated with mortality risk in these Latin American cities, with the strongest associations in So Paulo, the hottest city. The elderly are an important population for targeted prevention measures, but vulnerability by sex and education differed by city.

Rotavirus morbidity and mortality in children in Brazil

Objective. To study the epidemiology of rotavirus and estimate rotavirus- associated morbidity and mortality in children <= 5 years of age in Brazil in 2004 before introducing the rotavirus vaccine in Brazil`s National Immunization Program ( Programa Nacional de Imunizacoes, PNI). Methods. To estimate rotavirus morbidity, published studies ( 1999 - 2006) addressing incidence of acute diarrhea among children <= 5 years of age and frequency of rotavirus infection among children with diarrhea in Brazil were reviewed. Diarrhea episodes were divided into three categories of severity by level of care: mild cases requiring only home- based care; moderate cases requiring a visit to an outpatient healthcare facility; and severe cases requiring hospitalization. To estimate rotavirus mortality, information on the number of registered deaths from diarrhea in children <= 5 years of age was obtained from the Mortality Information System ( Sistema de Informacao, sobre Mortalidade, SIM) of Brazil`s public healthcare system ( Sistema Unico de Sa de, SUS) and the proportion of deaths due to rotavirus was calculated. Results. Rotavirus infections were estimated to cause 3 525 053 episodes of diarrhea, 655 853 visits to outpatient healthcare facilities, 92 453 hospitalizations, and 850 deaths of children <= 5 years of age each year in Brazil. Conclusion. Rotavirus infections are an important cause of child morbidity and mortality in Brazil.

Red Blood Cell Transfusions are Independently Associated with Intra-Hospital Mortality in Very Low Birth Weight Preterm Infants

Objective To test the hypothesis that red blood cell (RBC) transfusions in preterm infants are associated with increased intra-hospital mortality. Study design Variables associated with death were studied with Cox regression analysis in a prospective cohort of preterm infants with birth weight <1500 g in the Brazilian Network on Neonatal Research. Intra-hospital death and death after 28 days of life were analyzed as dependent variables. Independent variables were infant demographic and clinical characteristics and RBC transfusions. Results Of 1077 infants, 574 (53.3%) received at least one RBC transfusion during the hospital stay. The mean number of transfusions per infant was 3.3 +/- 3.4, with 2.1 +/- 2.1 in the first 28 days of life. Intra-hospital death occurred in 299 neonates (27.8%), and 60 infants (5.6%) died after 28 days of life. After adjusting for confounders, the relative risk of death during hospital stay was 1.49 in infants who received at least one RBC transfusion in the first 28 days of life, compared with infants who did not receive a transfusion. The risk of death after 28 days of life was 1.89 times higher in infants who received more than two RBC transfusions during their hospital stay, compared with infants who received one or two transfusions. Conclusion Transfusion was associated with increased death, and transfusion guidelines should consider risks and benefits of transfusion. (J Pediatr 2011; 159: 371-6).

Long-term follow-up of children with extrahepatic portal vein obstruction: impact of an endoscopic sclerotherapy program on bleeding episodes, hepatic function, hypersplenism, and mortality

Background: Endoscopic sclerotherapy (ES) has been the standard treatment for children with idiopathic extrahepatic portal vein obstruction (EHPVO). Portosystemic shunts are indicated when variceal bleeding cannot be controlled by ES. Recently, mesenteric left portal vein bypass was indicated as a surgical intervention and preventative measure for hepatic dysfunction in children with long-term EHPVO. Nevertheless, there is a lack Of published data confirming the extent of hepatic dysfunction, hypersplenism, and physical development in children with long-term follow-up. Method: We retrospectively verified the long-term outcomes in 82 children with EHPVO treated with ES protocol, focusing on mortality, control of bleeding, hypersplenism, and consequent hepatic dysfunction. Results: Of the children, 56% were free from bleeding after the initiation of ES. The most frequent cause of rebleeding was gastric varices (30%). Four patients had recurrent bleeding from esophageal varices (4.6%). Four patients underwent surgery as a consequence of uncontrolled gastric varices. There were no deaths. Most patients showed good physical development. We observed a mild but statistically significant drop in factor V motion, as well as leukocyte and platelet count. Conclusion: Endoscopic sclerotherapy is an efficient treatment for children with EHPVO. The incidence of rebleeding is low, and there was no mortality. Children develop mild liver dysfunction and hypersplenism with long-term follow-up. Only a few patients manifest symptoms of hypersplenism, portal biliopathy, or liver dysfunction before adolescence. (C) 2009 Elsevier Inc. All rights reserved.

Association between micronuclei frequency in pollen mother cells of Tradescantia and mortality due to cancer and cardiovascular diseases: A preliminary study in Sao Jose dos Campos, Brazil

The present study was designed to explore the correlation between the frequency of micronuclei in Trad-MN, measured across 28 biomonitoring stations during the period comprised between 11 of May and 2 of October, 2006, and adjusted mortality rates due to cardiovascular, respiratory diseases and cancer in Sao Jose dos Campos, Brazil, an area with different sources of air pollution. For controlling purposes, mortality rate due to gastrointestinal diseases (an event less prone to be affected by air pollution) was also considered in the analysis. Spatial distribution of micronuclei frequency was determined using average interpolation. The association between health estimators and micronuclei frequency was determined by measures of Pearson`s correlation. Higher frequencies of micronuclei were detected in areas with high traffic and close to a petrochemical pole. Significant associations were detected between micronuclei frequency and adjusted mortality rate due to cardiovascular diseases (r = 0.841, p = 0.036) and cancer (r = 0.890, p = 0.018). The association between mortality due to chronic obstructive pulmonary diseases was positive but did not reach statistical significance (r = 0.640, p = 0.172), probably because of the small number of events. Gastrointestinal mortality did not exhibit significant association with micronuclei frequency. Because the small number of observations and the nature of an ecological study, the present findings must be considered with caution and considered as preliminary. Further studies, performed in different conditions of contamination and climate should be done before considering Trad-MN in the evaluation of human health risk imposed by air pollutants. (C) 2009 Elsevier Ltd. All rights reserved.

A new large-caliber trocar for percutaneous endoscopic gastrostomy by the introducer technique in head and neck cancer patients

Background and study aims In many patients, percutaneous endoscopic gastrostomy (PEG) can be limited by digestive tract stenosis. PEG placement using an introducer is the safest alternative for this group of patients, but the available devices are difficult to implement and require smaller-caliber tubes. The aim of this study was to evaluate the modification of an introducer technique device for PEG placement with regard to the following: procedure feasibility, possibility of using a 20-Fr balloon gastrostomy tube, tube-related function and problems, complications, procedure safety, and mortality. Patients and methods Between March 2007 and February 2008, 30 consecutive patients with head and neck malignancies underwent introducer PEG placement with the modified device and gastropexy. Each patient was evaluated for 60 days after the procedure for the success of the procedure, infection, pain, complications, mortality, and problems with the procedure. Results The procedure was successful in all cases with no perioperative complications. No signs of stomal infection were observed using the combined infection score. The majority of patients experienced mild-to-moderate pain both in the immediate postoperative period and at 72 hours. One major early complication (3.3%) and two minor complications (6.7%) were observed. No procedure-related deaths occurred during the first 60 days after the procedure. Conclusion The device modification for PEG using the introducer technique is feasible, safe, and efficient in outpatients with obstructive head and neck cancer. In this series, it allowed the use of a larger-caliber tube with low complication rates and no procedure-related mortality.

Tuberculous meningitis in HIV-infected patients in Brazil: clinical and laboratory characteristics and factors associated with mortality

Background: Tuberculous meningitis (TBM) is a growing problem in HIV-infected patients in developing countries, where there is scarce data about this co-infection. Our objectives were to analyze the main features and outcomes of HIV-infected patients with TBM. Methods: This was a retrospective study of HIV-infected Brazilian patients admitted consecutively for TBM. All patients had Mycobacterium tuberculosis isolated from the cerebrospinal fluid (CSF). Presenting clinical and laboratory features were studied. Multivariate analysis was used to identify variables associated with death during hospitalization and at 9 months after diagnosis. Survival was estimated using the Kaplan-Meier method. Results: We included 108 cases (median age 36 years, 72% male). Only 15% had fever, headache, and meningeal signs simultaneously. Forty-eight percent had extrameningeal tuberculosis. The median CD4+ cell count was 65 cells/mu l. Among 90 cases, 7% had primary resistance to isoniazid and 9% presented multidrug-resistant strains. The overall mortality during hospitalization was 29% and at 9 months was 41%. Tachycardia and prior highly active antiretroviral therapy (HAART) were associated with 9-month mortality. The 9-month survival rate was 22% (95% confidence interval 12-43%). Conclusions: Clinical and laboratory manifestations were unspecific. Disseminated tuberculosis and severe immunosuppression were common. Mortality was high and the 9-month survival rate was low. Tachycardia and prior HAART were associated with death within 9 months of diagnosis. (C) 2009 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

MET Is Highly Expressed in Advanced Stages of Colorectal Cancer and Indicates Worse Prognosis and Mortality

The aim of the present study was to evaluate by immunohistochemistry the prognostic meaning of the tumor marker MET (hepatocyte growth factor) in patients submitted to surgical resection due to primary colorectal adenocarcinoma. Patients and Methods: A retrospective study was carried out that included 286 consecutive patients with colorectal adenocarcinoma, submitted to surgical resection at Barretos Cancer Hospital, from 1993 to 2002. The histopathological expression of the MET tumor marker was evaluated using an anti-protein monoclonal antibody against MET by the streptavidin-biotin-peroxidase technique. The expression of the tumor marker was semi-quantitative, and the slide samples were independently analyzed by three pathologists unaware of patient clinical and histopathological data. Results: The tumor marker expression was positive in 236 (79%) out of a total of 286 patients. This expression was statistically significantly different between stages I and IV (p=0.004), for overall survival (p=0.009), and for cancer-related mortality rates (p=0.022). However, no association between the tumor marker and recurrence (p=0.89) or disease-free interval (p=0.91) was observed. Conclusion: MET has shown significant expression at advanced stages of the disease, as well as for overall survival and cancer-related mortality rates demonstrating to be a valuable marker for poor prognosis in colorectal cancer patients.