Incidence of and risk factors for cardiovascular complications after thoracic surgery for noncancerous lesions.

OBJECTIVE: The purpose of this study was to determine the incidence of and risk factors for cardiovascular complications after thoracic surgery for noncancerous lesions. DESIGN: Retrospective cohort study. SETTING: A tertiary medical center. PARTICIPANTS: All consecutive patients undergoing either thoracotomy or thoracoscopy for noncancerous lesions between 2005 and 2011 were included. MEASUREMENTS AND MAIN RESULTS: The primary outcomes were the incidence and types of cardiovascular complications such as cardiac arrhythmias, cardiac arrest, heart failure, and myocardial ischemia during hospitalization. A total of 719 patients were recruited, 60% of whom had infections. The incidence of cardiovascular complications after thoracic surgery was 6.7% (48 of 719), of which cardiac arrhythmia was the most common (25 of 48, 52%). The multivariate risk regression analysis showed that age>55 years (risk ratio [RR]=4.0; 95% confidence interval [CI]=2.1-7.5; p<0.01), diabetes mellitus (RR=3.0; 95% CI=1.7-5.3; p<0.01), coronary artery disease (RR=4.8; 95% CI=2.3-10.2; p<0.01), duration of surgery>180 minutes (RR=2.6; 95% CI=1.3-5.1; p<0.01), intraoperative hypotension (RR=2.6; 95% CI=1.6-4.3; p<0.01), and positive fluid balance>2,000 mL (RR=2.5; 95% CI=1.4-4.5; p<0.01) were independent risk factors for cardiovascular complications. CONCLUSIONS: Knowledge of risk factors could help surgical teams to identify high risk patients and adjust modifiable risk factors including optimization of medical conditions, correction of intraoperative hypotension, and appropriate blood and fluid administration in order to reduce perioperative morbidity and mortality.

Association of positive fluid balance and cardiovascular complications after thoracotomy for noncancer lesions.

OBJECTIVE: The purpose of this study was to explore the influence of positive fluid balance on cardiovascular complications after thoracotomy for noncancer lesions. METHODS: After approval from an institutional review board, a retrospective cohort study was conducted. All consecutive patients undergoing thoracotomy between January 1, 2005 and December 31, 2011 in a single medical center were recruited. The primary outcome of the study was the incidence of cardiovascular complications, which were defined as cardiac arrhythmia, cardiac arrest, heart failure, myocardial ischemia, and pulmonary embolism. Univariable and multivariable risk regression analyses were used to evaluate the association between positive fluid balance and cardiovascular complications. RESULTS: A total of 720 patients were included in this study. The incidence of cardiovascular complications after thoracotomy for noncancer lesions was 6.7% (48 of 720). Patients with positive fluid balance >2,000 mL had a significantly higher incidence of cardiovascular complications than those with positive fluid balance ≤2,000 mL (22.2% versus 7.0%, P=0.005). Cardiac arrhythmias were the most common complication. Univariable risk regression showed that positive fluid balance >2,000 mL was a significant risk factor (risk ratio =3.15, 95% confident interval [CI] =1.44-6.90, P-value =0.004). After adjustment for all potential confounding variables during multivariable risk regression analysis, positive fluid balance >2,000 mL remained a strong risk factor for cardiovascular complications (risk ratio =2.18, 95% CI =1.36-3.51, P-value =0.001). Causes of positive fluid balance >2,000 mL included excessive hemorrhage (48%), hypotension without excessive hemorrhage (29.6%), and liberal fluid administration (22.4%). CONCLUSION: Positive fluid balance was a significant risk factor for cardiovascular complications. Strategies to minimize positive fluid balance during surgery for patients at high risk of cardiovascular complications include preparing adequate blood and blood products, considering appropriate hemoglobin level as a transfusion trigger, and adjusting the optimal dose of local anesthetic for intraoperative thoracic epidural analgesia.

The use of continuous thoracic paravertebral nerve block under direct vision for postoperative pain management in thoracic surgery.

OBJECTIVE: The purpose of the present study was to determine the quality of analgesia of continuous thoracic paravertebral nerve block after thoracic surgery by inserting a catheter under direct vision and assessing complications related to the analgesia technique. MATERIAL AND METHOD: Thirty patients with ASA I-III scheduled for pulmonary resection were enrolled in the present prospective study. Posterolateral thoracotomy was done by one surgeon. At the end of the operation before chest closure, a 16 G Touhy needle was inserted under direct vision at distance 5 cm from midline below incision interspace. The needle was advanced slowly until its tip bulged into the potential space, which is called paravertebral space, beneath the parietal pleura. Then, passing a catheter until the distal tip laid two to three intercostal spaces above the incision. A bolus of 15 to 20 ml of 0.5% levobupivacaine was given via a catheter and a continuous infusion with 0.25% levobupivacaine at rate 0.1 ml/kg/hr. Rescue treatment consisted of intravenous morphine and oral analgesic drugs. Numeric rating scale (NRS at rest, movement and cough), an amount of morphine consumption and complications related to analgesia were assessed at 2, 6, 12, 24, 48, 72, and 96 hours after operation. RESULTS: All patients completed the present study. The median numeric rating scale at rest in 24, 48, 72 and 96 hours after the operation was 2 (0-3), 0.5 (0-2),0 (0-2) and 0 (0-1) whereas the median numeric rating scale at deep breathing and coughing was 3.5 (2-5), 2 (2-4), 2 (1-3) and 2 (0-2). The median cumulative morphine consumption in 48 and 72 hours was 2 (0-4) and 3 (0-6) mg. Ten patients did not require additional morphine during the postoperative period. One patient experienced hypotension after a bolus of levobupivacaine for a few hours and recovered after supportive treatment. CONCLUSION: The use of continuous thoracic paravertebral blockade under direct vision technique offered satisfactory pain control and less complications. It could be considered as an alternative when thoracic epidural block is difficult to access.

Effect of combined genetic polymorphisms on lung cancer risk in northern Thai women.

Lung cancer is a major cause of cancer-related death in developed countries, and its incidence in developing countries is increasing. In Thailand, cancer incidences differ greatly from region to region, and lung cancer is the most common cancer in the northern Thai population. The polymorphic frequency of 10 genetic susceptibility genes and their association with lung cancer were examined in a northern Thai population: CYP1A1 (MspI), CYP1A1 (Ile462Val), CYP2E1 (PstI), CYP2E1 (DraI), GSTM1, GSTT1, MPO (AciI), OGG1 (Ser326Cys), TP53 (Arg72Pro), and MMP1(AluI). The 173 subjects were 91 lung cancer patients and 82 healthy volunteers. Although no significant association between any single genetic variant and lung cancer risk was observed, when genetic variants were analyzed in combination, a significant effect on lung cancer risk was found for the variant allele in a combination of five genes involved in oxidative stress and inflammatory response: GSTM1 (null), MPO (-463A), OGG1 (326Cys), TP53 (72Pro) (alias p53), MMP1 (2G). With a reference group of individuals carrying at least two wild-type genotypes of these five genes, it was found that an individual carrying three or more variant genotypes is at significantly higher risk of developing lung cancer with the increasing of odds ratios (OR) in concurrence with the number of variant genes. The OR was 2.41 (95% CI = 0.76-7.64), 3.90 (95% CI = 1.23-12.34), and 5.20 (95% CI = 1.31-20.54) for individuals carrying three, four, and five variants, respectively. After stratifying by sex, the OR was higher for women: OR 4.05 (95% CI = 0.44-36.94), 9.00 (95% CI = 0.95-84.89) and 18.00 (95% CI = 1.49-216.62) for three, four, and five variant genotypes, respectively. This augmented effect on lung cancer risk of variant genes involved in oxidative stress and inflammatory response in women with a low prevalence of smoking indicates their modifying effect on other risk factors, such as environmental cigarette smoke, air pollution, radon radiation, or infection of the airway. Confirmation would require further investigations with larger sample sizes.

Simplified approaches for the development of an ELISA to detect circulating autoantibodies to p53 in cancer patients.

BACKGROUND: The recognition that human tumors stimulate the production of autoantibodies has initiated the use of this immune response as serological markers for the early diagnosis and management of cancer. The enzyme-linked immunosorbent assay (ELISA) is the most common method used in detecting autoantibodies, which involves coating the microtiter plate with the tumor associated antigen (TAA) of interest and allowing serum antibodies to bind. The patient's sample is directly in contact with the coating antigen so the protein used for coating must be pure to avoid non-specific binding. In this study, a simplified method to selectively and specifically immobilize TAAs onto microtiter plates in order to detect circulating autoantibodies in cancer patients without prior purification process was described. Wild type full-length p53 protein was produced in fusion with biotin carboxyl carrier peptide (BCCP) or hexahistidine [(His)6] using pAK400 and pET15b(+) vectors, respectively. The recombinant p53 fusion protein produced was then subjected to react with either a commercial p53 monoclonal antibody (mAb) or sera from lung cancer patients and healthy volunteers in an enzyme-linked immunosorbent assay (ELISA) format. RESULTS: Both of the immobilized p53 fusion proteins as well as the purified (His)6-p53 fusion protein had a similar dose response of detection to a commercial p53 mAb (DO7). When the biotinylated p53-BCCP fusion protein was used as an antigen to detect p53 autoantibodies in clinical samples, the result showed that human serum reacted strongly to avidin-coated microwell even in the absence of the biotinylated p53-BCCP fusion protein, thus compromised its ability to differentiate weakly positive sera from those that were negative. In contrast, the (His)6-p53 protein immobilized directly onto Ni+ coated microplate was able to identify the p53 autoantibody positive serum. In addition, its reactivity to clinical serum samples highly correlated with those obtained from using purified p53 as an antigen (R = 0.9803, p < 0.0001). Moreover, this directly immobilized p53 antigen can clearly differentiate p53 autoantibody positive sera in cancer patients from healthy volunteers' sera. CONCLUSION: A method of coating directly and specifically TAAs onto a microtiter plate without the purification processes was developed in this study. Although in this study only one tumor antigen was examined, the simplicity and the ability of coated antigens to identify p53 specific autoantibodies in serum accurately might enable a larger panel of TAAs specific autoantibodies to be explored as serological markers for cancer.