Patient satisfaction after pulmonary resection for lung cancer: a multicenter comparative analysis.

BACKGROUND: Patient satisfaction reflects the perception of the customer about the level of quality of care received during the episode of hospitalization. OBJECTIVE: To compare the levels of satisfaction of patients submitted to lung resection in two different thoracic surgical units. METHODS: Prospective analysis of 280 consecutive patients submitted to pulmonary resection for neoplastic disease in two centers (center A: 139 patients; center B: 141 patients; 2009-2010). Patients' satisfaction was assessed at discharge through the EORTC-InPatSat32 module, a 32-item, multi-scale self-administered anonymous questionnaire. Each scale (ranging from 0 to 100 in score) was compared between the two units. Multivariable regression and bootstrap were used to verify factors associated with the patients' general satisfaction (dependent variable). RESULTS: Patients from unit B reported a higher general satisfaction (91.5 vs. 88.3, p = 0.04), mainly due to a significantly higher satisfaction in the doctor-related scales (doctors' technical skill: p = 0.001; doctors' interpersonal skill: p = 0.008; doctors' availability: p = 0.005, and doctors information provision: p = 0.0006). Multivariable regression analysis and bootstrap confirmed that level of care in unit B (p = 0.006, bootstrap frequency 60%) along with lower level of education of the patient population (p = 0.02, bootstrap frequency 62%) were independent factors associated with a higher general patient satisfaction. CONCLUSION: We were able to show a different level of patient satisfaction in patients operated on in two different thoracic surgery units. A reduced level of patient satisfaction may trigger changes in the management policy of individual units in order to meet patients' expectations and improve organizational efficiency.

Peak oxygen consumption measured during the stair-climbing test in lung resection candidates.

BACKGROUND: The stair-climbing test is commonly used in the preoperative evaluation of lung resection candidates, but it is difficult to standardize and provides little physiologic information on the performance. OBJECTIVE: To verify the association between the altitude and the V(O2peak) measured during the stair-climbing test. METHODS: 109 consecutive candidates for lung resection performed a symptom-limited stair-climbing test with direct breath-by-breath measurement of V(O2peak) by a portable gas analyzer. Stepwise logistic regression and bootstrap analyses were used to verify the association of several perioperative variables with a V(O2peak) <15 ml/kg/min. Subsequently, multiple regression analysis was also performed to develop an equation to estimate V(O2peak) from stair-climbing parameters and other patient-related variables. RESULTS: 56% of patients climbing <14 m had a V(O2peak) <15 ml/kg/min, whereas 98% of those climbing >22 m had a V(O2peak) >15 ml/kg/min. The altitude reached at stair-climbing test resulted in the only significant predictor of a V(O2peak) <15 ml/kg/min after logistic regression analysis. Multiple regression analysis yielded an equation to estimate V(O2peak) factoring altitude (p < 0.0001), speed of ascent (p = 0.005) and body mass index (p = 0.0008). CONCLUSIONS: There was an association between altitude and V(O2peak) measured during the stair-climbing test. Most of the patients climbing more than 22 m are able to generate high values of V(O2peak) and can proceed to surgery without any additional tests. All others need to be referred for a formal cardiopulmonary exercise test. In addition, we were able to generate an equation to estimate V(O2peak), which could assist in streamlining the preoperative workup and could be used across different settings to standardize this test.

Mechanism of miR-222 and miR-126 regulation and its role in asbestos-induced malignancy.

MiR-222 and miR-126 are associated with asbestos exposure and the ensuing malignancy, but the mechanism(s) of their regulation remain unclear. We evaluated the mechanism by which asbestos regulates miR-222 and miR-126 expression in the context of cancer etiology. An 'in vitro' model of carcinogen-induced cell transformation was used based on exposing bronchial epithelium BEAS-2B cells to three different carcinogens including asbestos. Involvement of the EGFR pathway and the role of epigenetics have been investigated in carcinogen-transformed cells and in malignant mesothelioma, a neoplastic disease associated with asbestos exposure. Increased expression of miR-222 and miR-126 were found in asbestos-transformed cells, but not in cells exposed to arsenic and chrome. Asbestos-mediated activation of the EGFR pathway and macrophages-induced inflammation resulted in miR-222 upregulation, which was reversed by EGFR inhibition. Conversely, asbestos-induced miR-126 expression was affected neither by EGFR modulation nor inflammation. Rather than methylation of the miR-126 host gene EGFL7, epigenetic mechanism involving DNMT1- and PARP1-mediated chromatin remodeling was found to upregulate of miR-126 in asbestos-exposed cells, while miR-126 was downregulated in malignant cells. Analysis of MM tissue supported the role of PARP1 in miR-126 regulation. Therefore, activation of the EGFR pathway and the PARP1-mediated epigenetic regulation both play a role in asbestos-induced miRNA expression, associated with in asbestos-induced carcinogenesis and tumor progression.

Prognostic relevance of programmed cell death protein 1/programmed death-ligand 1 pathway in thymic malignancies with combined immunohistochemical and biomolecular approach.

BACKGROUND: The aim of the study was to investigate Programmed cell Death protein 1 (PD-1) and Programmed Death-Ligand 1 (PD-L1) and their mRNA expression in thymic epithelial tumors (TETs). RESEARCH DESIGN AND METHODS: We analyzed 68 samples of formalin-fixed paraffin-embedded tissue (63 thymomas and 5 thymic carcinomas). PD-1 and PD-L1 protein expression were evaluated by immunohistochemistry, and mRNA expression was evaluated by real-time PCR. RESULTS: M/F ratio was 33/35, and median age was 60.5 years. Twenty patients had Myasthenia Gravis (MG). In the subgroup with large tumors (>5 cm), PD-L1 mRNA overexpression was significantly associated with worse prognosis vs. patients with no mRNA overexpression (p = 0.0083) and simultaneous PD-L1 immunostaining (>1%); PD-L1 mRNA overexpression was significantly associated with worse prognosis, respect to patient with PD-L1 negative immunostaining, and no PD-L1 mRNA overexpression (p = 0.0178). The elderly patients (>60 years) with large tumors showed worse prognosis (p = 0.0395). PD-L1 immunostaining (>50%) resulted to be significantly associated with MG. CONCLUSIONS: Our data suggest the potential involvement of the PD-1 and PD-L1 pathway in TETs' progression. According to our results, it may be helpful to design future trials with anti-PD-1 drugs to establish high-risk patients after surgery.

Four-miRNA Signature to Identify Asbestos-Related Lung Malignancies.

BACKGROUND: Altered miRNA expression is an early event upon exposure to occupational/environmental carcinogens; thus, identification of a novel asbestos-related profile of miRNAs able to distinguish asbestos-induced cancer from cancer with different etiology can be useful for diagnosis. We therefore performed a study to identify miRNAs associated with asbestos-induced malignancies. METHODS: Four groups of patients were included in the study, including patients with asbestos-related (NSCLCAsb) and asbestos-unrelated non-small cell lung cancer (NSCLC) or with malignant pleural mesothelioma (MPM), and disease-free subjects (CTRL). The selected miRNAs were evaluated in asbestos-exposed population. RESULTS: Four serum miRNAs, that is miR-126, miR-205, miR-222, and miR-520g, were found to be implicated in asbestos-related malignant diseases. Notably, increased expression of miR-126 and miR-222 were found in asbestos-exposed subjects, and both miRNAs are involved in major pathways linked to cancer development. Epigenetic changes and cancer-stroma cross-talk could induce repression of miR-126 to facilitate tumor formation, angiogenesis, and invasion. CONCLUSIONS: This study indicates that miRNAs are potentially involved in asbestos-related malignancies, and their expression outlines mechanism(s) whereby miRNAs may be involved in an asbestos-induced pathogenesis. IMPACT: The discovery of a miRNA panel for asbestos-related malignancies would impact on occupational compensation and may be utilized for screening asbestos-exposed populations.

Oxygen desaturation during maximal stair-climbing test and postoperative complications after major lung resections.

OBJECTIVE: Non-univocal conclusions have been published regarding the definition of oxygen desaturation in relation to postoperative outcome. We aimed to verify whether oxygen desaturation during a maximal stair-climbing test was associated with postoperative cardiopulmonary complications and to assess which definition of oxygen desaturation (oxygen saturation <90% or desaturation >4% with respect to rest level) discriminated better between complicated and uncomplicated patients. METHODS: Five hundred and thirty-six patients performing a maximal stair-climbing test prior to major lung resection were analyzed. All patients performed the test on room air. Patients with and without cardiopulmonary complications were compared in terms of several preoperative and operative characteristics by univariate analysis, including the presence of oxygen desaturation at peak exercise (saturation <90% or desaturation >4%). Logistic regression analysis was then performed and validated by bootstrap procedure to identify predictors of complications and to see whether the exercise oxygen desaturation retained its significancy after multivariable adjustment. RESULTS: Twenty-seven patients had an exercise oxygen saturation below 90%, but this parameter was not significantly associated with complications. Seventy-five patients experienced an exercise desaturation greater than 4%, which was a significant result associated with postoperative complications at univariate analysis (p=0.008) (36% complication rate). After adjusting for age, ppoFEV1, ppoDLCO, type of operation, height reached at stair-climbing test and cardiac co-morbidity, a desaturation greater than 4% retained its significance at logistic regression and proved to be stable at bootstrap. CONCLUSIONS: A stair-climbing test is an intense constant workload exercise, challenging a large amount of muscle mass, and appears particularly appropriate to elicit oxygen desaturation, which in turn may be a reliable marker of deficits in the oxygen transport system. A desaturation >4% appears a better cut-off definition than a saturation level <90% in predicting the occurrence of complications. The risk of complications was approximately two-fold higher in patients with oxygen desaturation >4% at peak exercise.

Enhanced recovery after thoracic surgery: patient information and care-plans.

Many studies have confirmed that the implementation of enhanced recovery after surgery (ERAS) protocols has the advantages of reducing the potential complications after thoracic surgery and the length of hospital stay. The ERAS program involves a multidisciplinary team, aimed at integrating evidence-based knowledge into clinical practice in order to reduce the patient's stress response to the surgical procedure and improve the response to stress, guaranteeing a combination of better outcomes and cost savings. All this would not be possible without the improvement of minimally invasive surgical techniques, progression of anesthesia, pain control, and careful patient preparation. In this setting, a preoperative personal counselling may play a key role to reduce stress, fear or anxiety and improve the morbidity of patients, enabling them to achieve functional and psychological compensatory mechanisms more quickly. Preoperative patient counselling, performed using verbal, written or multimedia materials, is crucial in order to achieve the goal of the ERAS project: making the patient a potentially active participant and the main character of his recovery, able to positively impact himself throughout the surgical and healing process. This report is aimed at evaluating patient information and care-plans in thoracic surgery, reviewing the available evidence on ERAS pathways, and demonstrating our ideal program as discussed and shared among the Italian Thoracic Surgery Units accredited in the video-assisted thoracic surgery (VATS) group.

Evaluation of expiratory volume, diffusion capacity, and exercise tolerance following major lung resection: a prospective follow-up analysis.

BACKGROUND: Lung resections determine a variable functional reduction depending on the extent of the resection and the time elapsed from the operation. The objectives of this study were to prospectively investigate the postoperative changes in FEV(1), carbon monoxide lung diffusion capacity (Dlco), and exercise tolerance after major lung resection at repeated evaluation times. METHODS: FEV(1), Dlco, and peak oxygen consumption (Vo(2)peak) calculated using the stair climbing test were measured in 200 patients preoperatively, at discharge, and 1 month and 3 months after lobectomy or pneumonectomy. Preoperative and repeated postoperative measures were compared, and a time-series, cross-sectional regression analysis was performed to identify factors associated with postoperative Vo(2)peak. RESULTS: One month after lobectomy, FEV(1), Dlco, and Vo(2)peak values were 79.5%, 81.5%, and 96% of preoperative values and recovered up to 84%, 88.5%, and 97% after 3 months, respectively. One month after pneumonectomy, FEV(1) percentage of predicted, Dlco percentage of predicted, and Vo(2)peak values were 65%, 75%, and 87% of preoperative values, and were 66%, 80%, and 89% after 3 months, respectively. Three months after lobectomy, 27% of patients with COPD had improved FEV(1), 34% had improved Dlco, and 43% had improved Vo(2)peak compared to preoperative values. The time-series, cross-sectional regression analysis showed that postoperative Vo(2)peak values were directly associated with preoperative values of Vo(2)peak, and postoperative values of FEV(1) and Dlco, and were inversely associated with age and body mass index. CONCLUSIONS: Our findings may be used during preoperative counseling and for deciding eligibility for operation along with other more traditional measures of outcome.

Physiopathology aspects of anatomical video-assisted thoracic surgery resections: current status and prospects of development.

Pulmonary lobectomy remains the gold standard therapy for early-stage lung cancer. With the spread of video-assisted thoracic surgery (VATS), surgeons began using this approach also to perform lobectomies, becoming progressively widespread worldwide. However some early-stage lung cancer patients are of questionable eligibility for open lobectomy being considered at high-risk to develop postoperative complications due to compromised pulmonary function or cardiopulmonary reserve. Herein we evaluate pathophysiology of VATS, focusing on: the correlation between the traditional predictors of outcome and overall complications, the current status of different VATS approaches and the role of VATS segmentectomy in high-risk patients, unable to tolerate lobectomy for their compromised cardiopulmonary reserve.

Intraoperative air leak measured after lobectomy is associated with postoperative duration of air leak.

OBJECTIVES: To verify the association between the air leak objectively measured intraoperatively (IAL) using the ventilator and the air leak duration after pulmonary lobectomy. METHODS: Prospective analysis on 111 patients submitted to pulmonary lobectomy (33 by video-assisted thoracic surgery). After resection, objective assessment of air leak (in milliliter per minute) was performed before closure of the chest by measuring the difference between a fixed inspired and expired volume, using a tidal volume of 8 ml/kg, a respiratory rate of 10 and a positive-end expiratory pressure of 5 cmH2O. A multivariable analysis was performed for identifying factors associated with duration of postoperative air leak. RESULTS: Average IAL was 158 ml/min (range 0-1500 ml/min). The best cut-off (receiver-operating characteristics analysis) associated with air leak longer than 5 days was 500 ml/min. Nine patients had IAL >500 ml/min (8%). They had a longer duration of postoperative air leak compared with those with a lower IAL (mean values, 10.1 days, SD 8.8 vs 1.5 days, SD 4.9 P < 0.001). The following variables remained associated with days of air leak duration after multivariable regression: left side resection (P = 0.018), upper site resection (P = 0.031) and IAL >500 ml/min (P < 0.001). The following equation estimating the days of air leak duration was generated: 1.7 + 2.4 × left side + 2.2 × upper site + 8.8 × IAL >500. CONCLUSIONS: The air leak measurement using the ventilator parameters after lung resection may assist in estimating the risk of postoperative prolonged air leak. An IAL > 500 ml/min may warrant the use of intraoperative preventative measures, particularly after video-assisted thoracic surgery lobectomy where a submersion test is often unreliable.

Video-assisted thoracic surgery lobectomy does not offer any functional recovery advantage in comparison to the open approach 3 months after the operation: a case matched analysis†.

OBJECTIVES: The objective of the present study was to compare functional loss [forced expiratory volume in one second to forced vital capacity ratio (FEV1), DLCO and VO2max reduction] after VATS versus open lobectomies. METHODS: We performed a prospective observational study on 195 patients who had a pulmonary lobectomy from June 2010 to November 2014 and who were able to complete a 3-months functional evaluation follow-up program. Since the VATS technique was our first choice for performing lobectomies from January 2012, we divided the patients into two groups: the OPEN group (112 patients) and the VATS group (83 patients). The open approach was intended as a muscle sparing/nerve sparing lateral thoracotomy. Fourteen baseline factors were used to construct a propensity score to match the VATS-group patients with their OPEN-group counterparts. These two matched groups were then compared in terms of reduction of FEV1, DLCO and VO2max (Mann-Whitney test). RESULTS: The propensity score analysis yielded 83 well-matched pairs of OPEN and VATS patients. In both groups, 3 months postoperatively, we found a reduction in FEV1, DLCO and VO2max values (OPEN patients: FEV1-10%, DLCO -11.9%, VO2max - 5.5%; VATS patients: FEV1-7.2%, DLCO-10.6%, VO2max-6.9%). The reductions in FEV1, DLCO and VO2max were similar to those in the two matched groups, with a Cohen effect size <0.2 for all the comparisons. CONCLUSIONS: In 3 months, both OPEN patients and VATS patients experienced a reduction in their preoperative functional parameters. VATS lobectomy does not offer any advantages in terms of FEV1, DLCO and exercise capacity recovery in comparison to the muscle-sparing thoracotomy approach.

Air leaks after lobectomy increase the risk of empyema but not of cardiopulmonary complications: a case-matched analysis.

PURPOSE: To assess whether the presence and duration of air leaks after lobectomy are associated with an increased incidence of cardiopulmonary complications. METHODS: Propensity score analysis was used on 726 patients undergoing pulmonary lobectomy from 1995 through 2004 to form three well-matched pairs of patients: patients with prolonged air leak (PAL) [> 7 days] and without air leak; patients with short air leak (SAL) [< or = 7 days] and without air leak; and patients with SAL and PAL. These matched groups were then compared to assess postoperative hospital stay and early outcome. RESULTS: Patients with SAL had a longer postoperative hospital stay compared to patients without air leak (8.6 days vs 7.8 days, respectively; p < 0.0001) but had similar morbidity and mortality. Patients with PAL had a longer postoperative hospital stay compared to patients without air leak (16.2 days vs 8.3 days, respectively; p < 0.0001) and with SAL (16.9 days vs 9 days, respectively; p < 0.0001), but similar cardiopulmonary complications were noted between the groups. Patients with PAL had a higher rate of empyema compared to patients without air leak and with SAL (8.2% vs 0%, p = 0.01 and 10.4% vs.1.1%, p = 0.01, respectively). CONCLUSIONS: The presence of air leak was not associated with an increased incidence of cardiopulmonary morbidity but was associated with an increased risk of empyema. Future prospective studies are needed to confirm safety of fast track in patients with air leak.

Carbon monoxide lung diffusion capacity improves risk stratification in patients without airflow limitation: evidence for systematic measurement before lung resection.

OBJECTIVE: In many centers, carbon monoxide lung diffusion capacity (DLCO) is still not routinely measured in all patients but only in patients with airflow limitation. The objective of the study was to assess the degree of correlation between forced expiratory volume in 1s (FEV1) and DLCO, and verify whether a low predicted postoperative DLCO (ppoDLCO) could have a role in predicting complications in patients without airflow limitation. METHODS: We analyzed 872 patients submitted to lung resection between January 2000 and December 2004 in two units measuring systematically DLCO before operation. Correlation between FEV1 and DLCO was assessed in the entire dataset and in different subsets of patients. A number of variables were then tested for a possible association with postoperative cardiopulmonary complications in patients with FEV1>80% by univariate analysis. Variables with p<0.10 at univariate analysis were used as independent variables in a stepwise logistic regression analysis (dependent variable: presence of cardiopulmonary morbidity), which was in turn validated by bootstrap analysis. RESULTS: The correlation coefficients between FEV1 and DLCO in the entire dataset and in different subsets of lung resection candidates (stratified by age, gender, cause of operation, airflow limitation) were all below 0.5, showing a modest degree of correlation. Two hundred and nineteen of the 508 patients (43%) with FEV1>80% had DLCO<80%. Moreover, in patients with FEV1>80%, logistic regression analysis showed that ppoDLCO<40% was a significant and reliable predictor of postoperative complications (p=0.004). CONCLUSION: The modest correlation between FEV1 and DLCO and the capacity of ppoDLCO to discriminate between patients with and without complications in subjects with a normal FEV1, warrants the routine measurement of DLCO in all candidates for lung resection, irrespective of their FEV1 value, in order to improve surgical risk stratification.

Clinical pathway for thoracic surgery in an Italian centre.

Clinical care pathways are developed to standardize postoperative patient care and the main impetus is to improve quality of care, decrease variation in care and reduce costs. We report the clinical pathway of care adopted at our centre since the introduction of Uniportal VATS program for major lung resections.

Recurrent air leak soon after pulmonary lobectomy: an analysis based on an electronic airflow evaluation†.

OBJECTIVES: The objective of this analysis was to evaluate the incidence and risk factors of recurrent air leak (RAL) occurring soon after pulmonary lobectomy based on electronic airflow measurements. METHODS: A prospective observational analysis of 129 consecutive patients managed with a single chest tube connected with an electronic chest drainage system. The incidence and timing of RAL among patients who had an air leak sealed within the first 24 postoperative hours was recorded. Stepwise logistic regression and bootstrap analyses were used to test the association of several baseline and surgical variables with RAL. RESULTS: A total of 95 patients (68%) had their air leak stopped within 24 h after the operation. Twelve patients had RAL (13%) after the first stop. All RALs occurred within the first 24 h from operation. Logistic regression showed that the presence of moderate-to-severe chronic obstructive pulmonary disease [COPD; forced expiratory volume in 1 s (FEV1) <80% and FEV1/forced vital capacity ratio <0.7] was an independent risk factor associated with RAL (P = 0.02, bootstrap frequency 83%). Seven of 27 (26%) patients with COPD had RAL, a proportion significantly higher than in patients without COPD (5 of 68, 7.3%, P = 0.03). CONCLUSIONS: A large proportion of patients with COPD developed RAL. In this high-risk group, we advise against chest tube removal in the first 24 h after operation, even in the case of absence or cessation of air leak.

Inability to perform maximal stair climbing test before lung resection: a propensity score analysis on early outcome.

OBJECTIVE: The objective of the present study was to assess whether patients unable to perform a preoperative maximal stair climbing test had an increased incidence of morbidity and mortality after major lung resection compared to patients who were able to exercise. METHODS: Three hundred and ninety one patients submitted to pulmonary lobectomy or pneumonectomy for lung cancer were analyzed. Forty-five of these patients were unable to perform a preoperative maximal stair climbing test for underlying comorbidities. Unadjusted and propensity score case matched comparisons were performed between patients who could and who could not perform a preoperative stair climbing test. Multi-variable analyses were then performed to identify predictors of morbidity and mortality, and were validated by bootstrap bagging. RESULTS: Patients who could not perform the stair climbing test had similar morbidity rates (31.1 vs. 35.6%, respectively, P=0.7), but higher mortality rates (15.6 vs. 4.4%, respectively, P=0.08) and deaths among complicated patients (50 vs. 12.5%, respectively, P=0.025), compared to propensity score matched patients who could perform the stair climbing test. Logistic regression analyses showed that the inability to perform the stair climbing test was an independent and reliable predictor of mortality (P=0.005) but not of morbidity (P=0.2). CONCLUSIONS: Patients unable to perform a preoperative maximal exercise test had an increased risk of mortality after major lung resection. Half of these patients did not survive postoperative complications, due to their decreased aerobic reserve caused by physical inactivity which made them unable to cope with the increased oxygen demand.

Impact of VEGF, VEGFR, PDGFR, HIF and ERCC1 gene polymorphisms on thymic malignancies outcome after thymectomy.

We aimed to analyze genotypes of VEGF-A, VEGFR2, Flt4, PDGFRα, HIF-1α and ERCC1 and their correlation with thymic tumor risk and patient outcome. DNA of 57 consecutive patients (43 thymomas and 14 thymic carcinomas) who underwent total thymectomy at our Institution was extracted from paraffin-embedded tissue. We selected polymorphisms in the following genes:HIF1-α (rs2057482T > C, rs1951795A > C, rs2301113C > A, rs10873142C > T, rs11158358G > C, rs12434438G > A, rs11549465C > T, rs11549467G > A), VEGF-A (rs2010963G > C, rs699947A > C), VEGFR-2 (rs2305948C > T, rs1870377T > A), VEGFR-3 (rs307826T > C, rs307821C > A), PDGFR-α (rs35597368C > T) and ERCC1 (rs11615A > G). Gene polymorphisms were determined by Real-Time PCR using TaqMan assays. As compared to the general population, the allele frequency of PDGFR-α rs35597368T was significantly higher (95% vs. 87%, p = 0.036), while the frequency of alleles HIF1-α rs2057482C (78% vs. 90%), rs1951795C (69% vs. 87%), rs2301113A (70% vs. 83%), rs10873142T (70% vs. 87%), rs11158358C (75% vs. 88%), rs12434438A (67% vs. 84%) were significantly lower. VEGFR-3 rs307821C frequency was significantly higher in thymomas vs. thymic carcinomas (79% vs. 72%, p = 0.0371). The following factors were significantly correlated with a longer overall survival: VEGFR-3 rs307826C, VEGFR-2 rs1870377A, PDGFR-α rs35597368T/C, HIF1-α rs2301113C, rs2057482C/T, rs1951795C, rs11158358G/C and rs10873142T/C, ERCC1 rs11615A (p < 0.05). Our results suggest, for the first time, that PDGFR-α, HIF-1α and VEGFR-3 SNPs are associated with thymic cancer risk and survival.

Combined circulating epigenetic markers to improve mesothelin performance in the diagnosis of malignant mesothelioma.

OBJECTIVES: Malignant mesothelioma (MM) is a highly aggressive tumor with poor prognosis. A major challenge is the development and application of early and highly reliable diagnostic marker(s). Serum biomarkers, such as 'soluble mesothelin-related proteins' (SMRPs), is the most studied and frequently used in MM. However, the low sensitivity of SMRPs for early MM limits its value; therefore, additional biomarkers are required. In this study, two epigenetically regulated markers in MM (microRNA-126, miR-126, and methylated thrombomodulin promoter, Met-TM) were combined with SMRPs and evaluated as a potential strategy to detect MM at an early stage. MATERIALS AND METHODS: A total of 188 subjects, including 45 MM patients, 99 asbestos-exposed subjects, and 44 healthy controls were prospectively enrolled, serum samples collected, and serum levels of SMRPs, miR-126 and Met-TM evaluated. Logistic regression analysis was performed to evaluate the diagnostic value of the three biomarkers. Using this approach, the performance of the '3-biomarker classifier' was tested by calculating the overall probability score of the MM and control samples, respectively, and the ROC curve was generated. RESULTS AND CONCLUSION: The combination of the three biomarkers was the best predictor to differentiate MM patients from asbestos-exposed subjects and healthy controls. The accuracy and cancer specificity was confirmed in a second validation cohort and lung cancer population. We propose that the combination of the two epigenetic biomarkers with SMRPs as a diagnosis for early MM overcomes the limitations of using SMRPs alone.

Predictors of early morbidity after major lung resection in patients with and without airflow limitation.

BACKGROUND: The aim of the present study was to identify predictors of morbidity after major lung resection for non-small cell lung carcinoma in patients with forced expiratory volume in 1 second (FEV1) greater than or equal to 70% of predicted and in those with FEV1 less than 70% of predicted. METHODS: Five hundred forty-four patients who underwent lobectomy or pneumonectomy from 1993 through 2000 were retrospectively analyzed. The patients were divided into two groups: group A (450 cases), with FEV1 greater than or equal to 70%, and group B (94 cases), with FEV1 less than 70%. Differences between complicated and uncomplicated patients were tested within each group. RESULTS: Morbidity rate was not significantly different between group A and group B (20.4% and 24.5%, respectively; p = 0.4). In group A, multivariate analysis showed that predicted postoperative FEV1 was the only significant independent predictor of complications. In group B, no significant predictor was identified. CONCLUSIONS: In patients with preoperative FEV1 less than 70% of predicted, predicted postoperative FEV1 was not predictive of postoperative morbidity. Thus, predicted postoperative FEV1 should not be used alone as a selection criteria for operation in these high-risk patients.

Pleural tent after upper lobectomy: a randomized study of efficacy and duration of effect.

BACKGROUND: The object of this study was to assess the efficay and maximum duration of effect of the pleural tent in reducing the incidence of air leak after upper lobectomy. METHODS: Two hundred patients who underwent upper lobectomy were prospectively randomized into two groups: 100 patients who underwent an upper lobectomy and a pleural tent procedure (group 1; tented patients) and 100 patients who underwent only an upper lobectomy and not a pleural tent procedure (group 2; untented patients). The preoperative, operative, and postoperative characteristics of both groups were compared. Then multivariate analyses were used to identify factors predictive of prolonged air leaks and their duration. The reduction of incidences of air leak in the two groups was subsequently compared during successive postoperative periods. RESULTS: No differences were detected between the two groups in terms of preoperative and operative characteristics. A significant reduction occurred in group 1 patients for the mean duration of air leak in days (2.5 vs 7.2 days; p < 0001), the number of days a chest tube was required (7.0 vs 11.2 days; p < 0.0001), the length of postoperative hospital stay in days (8.2 vs 11.6 days; p < 0.0001), and the hospital stay cost per patient (4,110 dollars vs 5,805 dollars; p < 0.0001). Logistic regression analyses showed that not having undergone a pleural tent procedure was the most significant predictive factor of the occurrence and duration of prolonged air leaks. A greater reduction in the duration of air leaks was observed before postoperative day 4 in group 1, and logistic regression analysis showed that having undergone a pleural tent procedure was the most significant predictive factor of air leaks that persisted for less than 4 days. CONCLUSIONS: Pleural tenting after upper lobectomy was a safe procedure that reduced the duration of air leaks and the hospital stay costs. The benefit from that procedure was achieved before postoperative day 4.