Ivan Felizardo Contrera Toro

Influence of p53 codon 72 exon 4, GSTM1, GSTT1 and GSTP1{*}B polymorphisms in lung cancer risk in a Brazilian population

PURPOSE Glutathione S-transferases (GST) modulates the effects of various cytotoxic and genotoxic agents, particularly those derived from benzo[a]pyrene, which is one of the main tobacco carcinogens. Both the mu 1 (GSTM1) and theta 1 (GSTT1) genes have a null variant allele in which the entire gene is absent. The GSTP1*B allele has an A to G transition at nucleotide 313 (codon 105) in exon 5, causing a change of isoleucine (Ile) to valine (Val), which affects the electrophile binding site of GSTP1 and results in an enzyme with reduced activity. Polymorphisms in these metabolizing enzymes may alter the response to benzo[a]pirene-induced DNA damage. Polymorphisms in p53 may also modulate the risk of lung cancer (LC) carcinogenesis. The aim of our study was to measure the frequency of GSTM1, GSTT1, GSTP1*B and p53 gene polymorphisms in a Brazilian population and determine the possible contribution of these genetic variations to LC risk. PATIENTS AND METHODS Genomic DNA was obtained from 200 Brazilian patients with LC and 264 blood donors (control group). All samples were analyzed by PCR and PCR-RFLP to determine GSTM1, GSTT1, GSTP1*B and p53 codon 72 genotypes. Multiple logistic regressions were used to adjust for confounding factors in this case-control study. RESULTS No statistical significance was observed between GSTM1, GSTT1 and GSTP1*B genetic polymorphisms, either isolated or combined, with LC incidence in the studied population. However, our data showed a higher frequency of p53 codon 72 A/P plus P/P genotype in African-Brazilian than Caucasian-Brazilian patients with LC, and we also found a higher frequency of the P/P genotype of the p53 gene in non-smokers compared to smokers with LC. CONCLUSIONS Genetic polymorphisms of GST and p53 codon 72 did not increase the risk of LC in Brazilian patients. The A/P plus P/P genotype of p53 codon 72 is more common in LC patients with African ethnical background and the P/P genotype more prevalent in non-smoking related LC.

The use of SPECT in preoperative assessment of patients with lung cancer

Perfusion scintigraphy is the most frequently used method for the regional assessment of pulmonary function in candidates for pulmonary resection with borderline respiratory function. This method provides two-dimensional images, and it considers all the segments of the pulmonary lobes as having the same volume and function, without considering the spatial overlapping of pulmonary areas with different function. As single-photon emission computed tomography (SPECT) provides tomographic imaging, this could be a more precise method for regional assessment. In this study, the postoperative predicted forced expiratory volume in one second (FEV1) (FEV1,ppo) was calculated in 26 patients with lung cancer using FEV1, quantitative lung perfusion scan with planar acquisition (PA) and quantitative lung perfusion scan with tomographic imaging (SPECT). The estimated FEV1,ppo values obtained using both methods were compared with FEV1 values measured after surgery (mean: 48±44 days; range: 15–180 days; median: 32 days). The Pearsons linear correlation coefficient was 0.8840 for FEV1,ppo estimated by PA and 0.8791 for FEV1,ppo estimated by SPECT. The linear correlation coefficient for lobectomy was greater than the coefficient for pneumonectomy using both methods. In conclusion, both methods show good correlation for real postoperative pulmonary function without demonstrating single-photon emission computed tomography superiority over planar acquisition, and both methods were more effective for estimating postoperative predicted forced expiratory volume in one second in lobectomies than in pneumonectomies.

Characterization of Pulmonary and Systemic Inflammatory Responses Produced by Lung Re-expansion After One-Lung Ventilation

OBJECTIVES To characterize the pulmonary and systemic inflammatory responses of rats undergoing 1-hour or 3-hour one-lung ventilation (OLV) with subsequent 1-hour lung re-expansion. DESIGN A prospective, randomized, controlled animal experiment. SETTING University laboratory. PARTICIPANTS Thirty male Wistar rats were used. INTERVENTIONS Rats were subjected to 1- or 3-hour OLV followed or not by 1-hour lung re-expansion. Control rats received no ventilation. MEASUREMENTS AND MAIN RESULTS Pulmonary protein extravasation, pulmonary myeloperoxidase (MPO) activity, cytokine levels in serum and bronchoalveolar lavage (BAL), counts of total and differential cells in BAL fluid, gasometric data, and mean arterial blood pressure (MABP) were all evaluated. Bronchial occlusion for 1 or 3 hours with no lung re-expansion did not significantly change the protein extravasation in the right and left lungs compared with the control group. However, rats submitted to 1- or 3-hour OLV followed by lung re-expansion exhibited pulmonary edema formation and neutrophil recruitment as well as a higher MPO activity in comparison with control rats. Increased levels of interleukin (IL)-6, IL-1β, and tumor necrosis factor-α in BAL fluid were observed. Increased levels of IL-6 and IL-10 in serum also were detected. Blood gas and MABP did not differ between groups. CONCLUSIONS Lung re-expansion after bronchial occlusion evokes an acute lung inflammatory response, which has been shown to be more pronounced in long periods of bronchial occlusion in terms of cytokine inflammatory response. In addition, the magnitude of this inflammatory response also can be detected systemically.

Predictors of quality-of-life improvement following pulmonary resection due to lung cancer

CONTEXT AND OBJECTIVE There is increasing involvement of health professionals in organizing protocols to determine the impact of lung surgery on functional state and activities of daily living, with the aim of improving quality of life (QoL). The objective of this study was to investigate predictors of QoL improvement among patients undergoing parenchyma resection due to lung cancer. DESIGN AND SETTING Prospective study, at teaching hospital of Universidade Estadual de Campinas (Unicamp). METHODS 36 patients with lung cancer diagnosis were assessed before surgery and on the 30th, 90th and 180th days after surgery. The Short-Form Health Survey (SF-36) was used as the dependent variable. The independent variables were the Hospital Anxiety and Depression (HAD) scale, a six-minute walking test (6-MWT), a visual analogue scale for pain, forced vital capacity (FVC), type of surgery and use of radiotherapy and chemotherapy. Generalized estimation equations (GEE) were utilized. RESULTS The median age for these 20 men and 16 women was 55.5 +/- 13.4 years. Both FVC and 6-MWT were predictors of improvement in the physical dimensions of QoL (p = 0.011 and 0.0003, respectively), as was smaller extent of surgical resection (p = 0.04). The social component of QoL had improved by the third postoperative month (p = 0.0005). CONCLUSION The predictors that affected QoL positively were better FVC and 6-MWT results and less extensive lung resection. Three months after the surgery, an improvement in social life was already seen.

Clinical variables of preoperative risk in thoracic surgery

CONTEXT Pulmonary complications are the most common forms of postoperative morbidity in thoracic surgery, especially atelectasis and pneumonia. The first step in avoiding these complications during the postoperative period is to detect the patients that may develop them. OBJECTIVE To identify risk variables leading to early postoperative pulmonary complications in thoracic surgery. DESIGN Prospective study. SETTING Hospital das Clínicas, Faculdade de Ciências Médicas, Universidade Estadual de Campinas. PATIENTS 145 patients submitted to elective surgery were classified as low, moderate and high risk for postoperative pulmonary complications using a risk assessment scale. PROCEDURES The patients were followed up for 72 hours after the operation. Postoperative pulmonary complications were defined as atelectasis, pneumonia, tracheobronchitis, wheezing, prolonged intubation and/or prolonged mechanical ventilation. MAIN MEASUREMENTS Univariate analysis was applied in order to study these independent variables: age, nutritional status, body mass index, respiratory disease, smoking habit, spirometry and surgery duration. Multivariate logistic regression analysis was performed in order to evaluate the relationship between independent and dependent variables. RESULTS The incidence of postoperative complications was 18.6%. Multivariate logistic regression analysis showed that the variables increasing the chances of postoperative pulmonary complications were wheezing (odds ratio, OR = 6.2), body mass index (OR = 1.15), smoking (OR = 1.04) and surgery duration (OR = 1.007). CONCLUSION Wheezing, body mass index, smoking and surgery duration increase the chances of postoperative pulmonary complications in thoracic surgery

Avaliação da qualidade de vida em pacientes submetidos a ressecção pulmonar por neoplasia

OBJECTIVE To evaluate the health-related quality of life of patients submitted to resection of the pulmonary parenchyma due to neoplasia. METHODS The Medical Outcomes Study 36-item Short-Form Health Survey was used to evaluate patients in the preoperative period and on postoperative days 30, 90 and 180. We used the GEE statistical model, in which the dependent variable (quality of life) changes for each patient over the course of the evaluation. Independent variables were gender, age, educational level, type of surgery, radiotherapy, chemotherapy, forced vital capacity and 6-minute walk test. The level of significance adopted was 5%. RESULTS The final study sample comprised 36 patients, 20 of whom were men. Of those 36 patients, 17 were submitted to lobectomy, 10 to pneumonectomy, 6 to segmentectomy, and 3 to bilobectomy. Chemotherapy was used in 15 patients, radiotherapy in 2, and a combination of radiotherapy and chemotherapy in 2. Improved quality of life was seen in the following domains: social (on postoperative day 90); physical/functional (some patients presenting better forced vital capacity and 6-minute walk test performance); and physical (in patients undergoing smaller resections). Lowered quality of life was seen in the following domains: social (for female patients); physical/social (resulting from radiotherapy, chemotherapy or both); and physical/functional (by postoperative day 30). CONCLUSIONS It is important that studies evaluating the various determinants of quality of life, as well as the impact that cancer treatment modalities have on such variables, be conducted. The knowledge provided by such studies can contribute to improving the quality of life of patients undergoing pulmonary resection due to neoplasia.

Broncoscopia para remoção de corpo estranho: onde está o atraso?

This was a retrospective analysis of the medical charts of 145 patients treated at the Bronchoscopy and Thoracic Surgery Clinic of the Hospital das Clínicas da Universidade Estadual de Campinas (HC-Unicamp, State University of Campinas Hospital das Clínicas) over a period of 10 years. There was a significant difference related to the site of first medical visit (Unicamp-HC versus other institutions) in terms of the time elapsed between the suspicion of bronchial aspiration and the actual respiratory endoscopic examination. However, no significant difference was found in the rate of positive results. The low number of referral centers that provide emergency respiratory endoscopy can negatively influence the treatment of patients under suspicion of bronchial aspiration, jeopardizing the overall recovery in the mid- and long-term.

Mesotelioma maligno de pleura com associação etiológica a asbesto: a propósito de três casos clínicos

O mesotelioma maligno de pleura (MM) e tumor de ocorrencia rara em nosso meio e tem-se mostrado, quando em elevada incidencia, relacionado a exposicao pregressa a asbesto ou amianto nas series descritas em outros paises. OBJETIVO. A partir de casos clinicos atendidos no Hospital de Clinicas da Unicamp, procurou-se evidenciar tal associacao epidemiologica, visando alertar profissionais medicos quanto a possivel elevacao da incidencia de tal tumor nesta decada e, futuramente, por caracteristicas proprias da historia natural desse tipo de tumor. METODOS. Sao descritos tres casos de MM de pleura ocorridos na regiao de Campinas, SP, num periodo de dois anos, dos pontos de vista clinico, laboratoriais complementares e anatomopatologico, incluindo minuciosa investigacao anamnesica ocupacional e ambiental. RESULTADOS. Todos os casos foram confirmados do ponto de vista anatomopatologico, incluindo microscopia eletronica, como casos de MM. Os tres casos mostraram relacao epidemiologica, comprovada por meio de historia ocupacional, com exposicao a asbesto no passado. Um dos casos teve exposicao ocupacional pregressa de curta duracao (cerca de um ano); outro teve exposicao domestica a partir de asbesto trazido do ambiente de trabalho por seu pai, durante sua infância, e o terceiro caso com contaminacao ocupacional indireta. CONCLUSAO. A ocorrencia de MM de pleura relacionada a exposicao a asbesto, no passado, parece ser realidade em nosso meio, como mostram estes tres casos clinicos. Destaca-se a necessidade da anamnese ocupacional e ambiental detalhadas na abordagem desses casos, alertando-se para maior atencao no diagnostico dos tumores primarios da pleura e do peritonio, nos proximos anos, em funcao de provavel aparecimento de novos casos relacionados a exposicao a asbesto pregressa, tendo em vista o intervalo de tempo entre o inicio da manipulacao do asbesto em nosso pais e o aparecimento destes primeiros casos coincidir com o tempo de latencia medio esperado para a ocorrencia de MM. Destacam-se, ainda, as necessidades de definicao precisa de criterios diagnosticos, para esse tipo de tumor, e criacao de registro centralizado de casos.

Incidência de pneumotórax residual após simpatectomia torácica videotoracoscópica com e sem drenagem pleural e sua possível influência na dor pós-operatória

OBJECTIVE To determine the incidence of residual pneumothorax after video-assisted thoracic sympathectomy, with and without postoperative pleural drainage, and to evaluate the possible influence of this type of pneumothorax on postoperative pain within the first 28 postoperative days. METHODS All patients presenting symptoms consistent with primary palmoplantar hyperhidrosis and treated at the Thoracic Surgery Outpatient Clinic of the State Hospital of Sumaré between July and December of 2006 were included. All were submitted to sympathectomy up to the third ganglion using video-assisted thoracoscopy and were randomized to receive or not receive postoperative pleural drainage for 3 h. Chest X-rays and low-dose computed tomography scans of the chest were performed on the first postoperative day in order to determine the incidence of residual pneumothorax. At different time points up to postoperative day 28, patient pain was assessed using a visual numeric scale and by measuring the quantity of opioid analgesics required. RESULTS This study comprised 56 patients, 27 submitted to bilateral pleural drainage and 29 not submitted to drainage. There was no statistical difference between the two groups in terms of the incidence of post-sympathectomy residual pneumothorax. Residual pneumothorax diagnosed through any of the methods did not influence pain within the first 28 postoperative days. CONCLUSION Performing closed pleural drainage for 3 h immediately after video-assisted thoracic sympathectomy did not affect lung re-expansion or the incidence of residual pneumothorax. When residual pneumothorax was present, it did not affect pain within the first 28 postoperative days.

Fatores prognósticos em complicações pós-operatórias de ressecção pulmonar: análise de pré-albumina, tempo de ventilação mecânica e outros

Objective: To determine whether pre-operative nutritional status and post-operative time on mechanical ventilation, as well as others factors, are correlated with post-operative complications (general or pulmonary) in patients undergoing elective thoracic surgery. Methods: A prospective study was conducted, involving 71 patients undergoing elective pulmonary resection. The data collected pre-operatively included gender, age, smoking status, pre-albumin level, lymphocyte count, and body mass index. The peri-operative data included type of surgery and surgical time, as well as post-operative time on mechanical ventilation. Results: Post-operative complications were found to correlate with low pre-albumin concentration, type of resection, surgical time, and post-operative time on mechanical ventilation. Surgical time and post-operative time on mechanical ventilation were also implicated in the post-operative pulmonary complications observed in 22 (30.99%) of the patients studied. Conclusion: Our results suggest that pre-albumin concentration, type of surgery and surgical time, as well as post-operative time on mechanical ventilation, serve as predictive indices of post-operative complications in patients undergoing elective pulmonary resection. In the analysis of the post-operative pulmonary complications, statistically significant correlations were found between such complications and increases in surgical time or post-operative time on mechanical ventilation.