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.

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.

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.

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.

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.

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.

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.

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.

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.

Real-time database drawn from an electronic health record for a thoracic surgery unit: high-quality clinical data saving time and human resources.

OBJECTIVES: The aim of the present study was to verify whether the implementation of an electronic health record (EHR) in our thoracic surgery unit allows creation of a high-quality clinical database saving time and costs. METHODS: Before August 2011, multiple individuals compiled the on-paper documents/records and a single data manager inputted selected data into the database (traditional database, tDB). Since the adoption of an EHR in August 2011, multiple individuals have been responsible for compiling the EHR, which automatically generates a real-time database (EHR-based database, eDB), without the need for a data manager. During the initial period of implementation of the EHR, periodic meetings were held with all physicians involved in the use of the EHR in order to monitor and standardize the data registration process. Data quality of the first 100 anatomical lung resections recorded in the eDB was assessed by measuring the total number of missing values (MVs: existing non-reported value) and inaccurate values (wrong data) occurring in 95 core variables. The average MV of the eDB was compared with the one occurring in the same variables of the last 100 records registered in the tDB. A learning curve was constructed by plotting the number of MVs in the electronic database and tDB with the patients arranged by the date of registration. RESULTS: The tDB and eDB had similar MVs (0.74 vs 1, P = 0.13). The learning curve showed an initial phase including about 35 records, where MV in the eDB was higher than that in the tDB (1.9 vs 0.74, P = 0.03), and a subsequent phase, where the MV was similar in the two databases (0.7 vs 0.74, P = 0.6). The inaccuracy rate of these two phases in the eDB was stable (0.5 vs 0.3, P = 0.3). Using EHR saved an average of 9 min per patient, totalling 15 h saved for obtaining a dataset of 100 patients with respect to the tDB. CONCLUSION: The implementation of EHR allowed streamlining the process of clinical data recording. It saved time and human resource costs, without compromising the quality of data.

The use of the Thoracic Morbidity and Mortality system for the internal analysis of performance: a case-matched temporal audit.

OBJECTIVES: The aim of the present study was to evaluate the usefulness of the Thoracic Morbidity and Mortality (TMM) scoring system in auditing the quality of care of our unit. METHODS: We analysed the performance of our unit comparing the incidence of complications and mortality occurring after anatomic lung resections during two different periods: early period (January 2000 to December 2009: 830 lobectomy, 134 pneumonectomy and 78 segmentectomy) and recent period (January 2010 to August 2012: 191 lobectomy, 8 pneumonectomy and 19 segmentectomy). The cardiopulmonary complications as traditionally defined in the European Society of Thoracic Surgeons (ESTS) database were also classified according to the TMM system: this method grades the postoperative adverse events from 1 to 5 reflecting an increasing severity of management regardless the type of complication. Complications graded higher than 2 are regarded as major complications. To account for confounders, several baseline and surgical factors were used to build a propensity score that was applied to match the patients of the most recent group with their early-group counterparts. These two matched groups were compared in terms of cardiopulmonary morbidity (codified by ESTS definitions) and mortality rates and incidence of major complications according to the TMM system. RESULTS: The propensity score analysis yielded 209 well-matched pairs of patients operated on in the two periods. The two groups had similar rates of ESTS-defined cardiopulmonary complications (recent: 38 patients vs early: 37 patients, P = 0.9). The use of the TMM system revealed a higher incidence of major (grade > 2) complications rate in the recent period (recent: 29 patients vs early: 14 patients, P = 0.02). CONCLUSIONS: The TMM scoring system for classifying the postoperative complications revealed a decline of quality of care of our unit otherwise undetected by applying traditional outcome measures. This tool can be used as an additional graded outcome endpoint to refine internal audit of performance.

Can maximal inspiratory and expiratory pressures during exercise predict complications in patients submitted to major lung resections? A prospective cohort study.

OBJECTIVES: The measurement of maximal inspiratory pressure (PImax) and maximal expiratory pressure (PEmax) generated at the mouth is an accepted non-invasive clinical method for evaluating the strength of respiratory muscles. The aim of our study was to verify whether PImax and PEmax measured before and after a symptom-limited stair-climbing test are associated with complications in patients submitted to major lung resections. METHODS: In a prospective cohort study of 283 consecutive patients submitted to lobectomy (231) or pneumonectomy (52) with a preoperative symptom-limited stair-climbing test, PImax and PEmax were measured before and immediately after the exercise. PImax and PEmax values were expressed as percentages of predicted values. ΔPImax and ΔPEmax were defined as the percentage difference between the pre- and postexercise values. Logistic regression analysis and the bootstrap resampling technique were performed to identify predictors of cardiopulmonary complications. RESULTS: On average, PImax dropped by 3.6% and PEmax increased by 0.8% after the exercise. In total, 173 patients (61%) experienced a reduction in their PImax after exercise, while 150 (53%) had their PEmax reduced. Postoperative cardiopulmonary complications occurred in 74 patients (26%). Complicated patients had a greater reduction in their PImax compared with non-complicated patients (8.7% vs 2.1%, P = 0.03), whereas ΔPEmax was similar in complicated and non-complicated patients (0.7% vs 1.3%, P = 0.5). Receiver operating characteristic analysis indicated that the best cut-off for predicting complications was a ΔPImax of 10%. Stepwise logistic regression analysis and bootstrap confirmed that ΔPImax of >10 was associated with cardiopulmonary complications after adjusting for baseline and surgical factors (ΔPImax regression coefficient -0.02, P = 0.09, bootstrap frequency 51%). A progressive increase in complications was observed in patients with greater reduction in ΔPImax after exercise, particularly for values >10% reduction. CONCLUSION: The measurement of PImax at the mouth during exercise represents an additional parameter that can be used to refine risk stratification of lung resection candidates and to identify patients who may benefit from inspiratory muscle training.

Major morbidity after lung resection: a comparison between the European Society of Thoracic Surgeons Database system and the Thoracic Morbidity and Mortality system.

OBJECTIVE: The Thoracic Morbidity and Mortality (TM&M) classification system is a method for univocally coding the postoperative adverse events by their complexity of management. The aim of the present study was to compare the distribution of the severity of complications according to the TM&M system versus the distribution according to the classification proposed by European Society of Thoracic Surgeons (ESTS) Database in a population of patients submitted to lung resection in our unit. METHODS: 457 patients with any type of complications (326 lobectomy, 60 pneumonectomy, 71 wedge/segmentectomy) out of 1,518 patients submitted to pulmonary resections (January 2000-April 2011) were analyzed. Each complication was graded from I to V (TM&M system), reflecting an increasing severity of management. We verified the distribution of the different grades of complications and analyzed their frequency among those defined as "major cardio-pulmonary complications" by the ESTS Database. RESULTS: According to the TM&M system, 0.6% of complications were regarded as grade I, 66.3% as grade II, 9.5% as grade IIIa, 4.4% as grade IIIb, 6.8% as grade IVa, 3.3% as grade IVb and 9.1% as grade V. According to the ESTS definitions, 290 complications were regarded as "major". Sixty two percent of them were reclassified as minor complications (grade I or II) by the TM&M classification system. CONCLUSIONS: The application of the TM&M grading system questions the traditional classification of complications following lung resection. This grading system may be used as an additional endpoint for outcome analyses.

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.

Regulated tailored suction vs regulated seal: a prospective randomized trial on air leak duration.

OBJECTIVE: The objective of this study was to compare the air leak duration of two regulated chest tube modes following pulmonary lobectomy. METHODS: This is a prospective randomized trial on 100 consecutive pulmonary lobectomies (2010-11) performed for lung cancer. A single 24-French chest tube was connected to an electronic system capable of maintaining the pleural pressure within preset values (regulated suction mode) or within a physiological range (regulated seal mode). Patients were randomized to two groups: Group 1, regulated individualized suction (range: -11 to -20 cmH2O, according to lobectomy type); Group 2, regulated seal (-2 cmH2O). The main endpoint was the duration of air leak (h) calculated from the end of the operation to a value consistently below 20 ml/min. Patients with prolonged air leak (>168 h) were connected to a portable device before discharge. Their air leak duration was considered as 192 h. The sample size was calculated to detect 1-day difference in air leak duration with a statistical power of 80%. RESULTS: The two groups were well matched for several baseline and surgical characteristics. No crossovers occurred between groups. The average air leak duration (Group 1: 28 vs Group 2: 22.2, P = 0.6), and the number of patients with prolonged air leak (Group 1: 5 vs Group 2: 4, P = 0.7) and with other complications (Group 1: 6 patients vs Group 2: 7 patients, P = 0.9) were similar between the groups. Sixteen patients of Group 1 and 21 of Group 2 had an air leak present immediately after extubation. Among them, patients of Group 2 (regulated seal) had an air leak lasting 34.5 h less than those of Group 1 (regulated suction) (52.9 vs 87.4, P = 0.07). CONCLUSIONS: Regulated seal is as effective and safe as regulated suction in managing chest tubes following lobectomy. This information demonstrates with objective data the non-superiority of regulated suction vs regulated seal and may assist in future investigations on regulated pleural pressure.

Maspin expression is a favorable prognostic factor in non-small cell lung cancer.

OBJECTIVE: To evaluate prognostic impact of maspin expression in patients with resected non-small cell lung cancer (NSCLC). STUDY DESIGN: From 1996 to 2001, 439 patients underwent radical surgery for NSCLC at the Polytechnic University of the Marche Region. Maspin expression was detected as cytoplasmic and nuclear staining of neoplastic cells. For cytoplasmic staining, cases were classified as negative, low positive, and high positive. In positive cases, intensity of staining was also considered and scored. A similar classification was used for nuclear staining, but intensity was not considered. RESULTS: The analysis showed that smoking history, pathologic stage of disease, N status, histologic grading, sex, and Eastern Cooperative Oncology Group performance status had a prognostic impact on overall survival (OS). Expression of maspin was also found to be an independent prognostic factor. A statistically significant longer OS was seen in patients with higher compared with lower expression of nuclear maspin, and poorer OS was present in patients with a higher intensity of cytoplasmic staining. Nuclear expression of maspin was also found to be an independent prognostic factor at multivariate analysis. CONCLUSION: Results suggest that overexpression of maspin correlates with favorable prognosis in NSCLC. and may be a useful clinical marker.

Performance at preoperative stair-climbing test is associated with prognosis after pulmonary resection in stage I non-small cell lung cancer.

BACKGROUND: This investigation evaluated whether the performance at a preoperative symptom-limited stair-climbing test was a prognostic factor in resected pathologic stage I non-small cell lung cancer (NSCLC). METHODS: Observational analysis was performed on a prospective database that included 296 patients who underwent pulmonary lobectomy for pathologic stage T1 N0 or T2 N0 NSCLC (2000 to 2008). Patients who received induction chemotherapy were excluded. Survival was calculated by the Kaplan-Meyer method. The log-rank test was used to assess differences in survival between groups. The relationships between survival and baseline and clinical variables were determined by Cox multivariate analyses. RESULTS: Median follow-up was 43 months. The best cutoff associated with prognosis was an 18-meter stair climb. Median (months) survival and 5-year survival of patients who climbed more than 18 meters were significantly longer than those who climbed less than 18 meters (97 vs 74; 77% vs 54%, p=0.001). Cox regression model (hazard ratio) showed that climbing more than 18 meters (0.5; p=0.003), diffusion capacity of the lung for carbon monoxide (0.98; p=0.02), and pT stage (1.8; p=0.02) were independent prognostic factors. Patients who climbed less than 18 meters had increased deaths from cancer (24% vs 15%, p=0.1) or other causes (19% vs 9%, p=0.02). CONCLUSIONS: Preoperative cardiopulmonary fitness is a significant prognostic factor in patients after resection for early-stage NSCLC. Interventions aimed at improving exercise tolerance can be useful to improve long-term prognosis after NSCLC operations.

Predicted versus observed peak oxygen consumption after major pulmonary resection.

BACKGROUND: The aim of this study was to verify the accuracy of predicted postoperative peak VO(2) in predicting the actual peak VO(2) after major pulmonary resection. METHODS: This was a prospective longitudinal series of 110 consecutive patients who underwent lobectomy (101 patients) or pneumonectomy (9 patients), with complete preoperative and postoperative (3 months) cardiopulmonary exercise testing (CPET). Predicted postoperative peak VO(2) was calculated by subtracting from the preoperative peak VO(2) the contribution of unobstructed pulmonary segments removed during operation. Predicted postoperative peak VO(2) and actual postoperative peak VO(2) were compared by the paired sign test. RESULTS: The average value of preoperative peak VO(2) was 16.8 mL/kg/min or 64.1% of predicted. The actual value of postoperative peak VO(2) was 15.9 mL/kg/min or 64.4% of predicted. The actual postoperative peak VO(2) was higher than the predicted postoperative peak VO(2) (15.9 versus 13.1 mL/kg/min; p < 0.0001; 64.4% versus 50.1%; p < 0.0001). Of the 23 patients with a predicted postoperative peak VO(2) less than 10 mL/kg/min, 19 had an actual postoperative peak VO(2) greater than 10 mL/kg/min (average value 13.3 mL/kg/min). All 11 patients with a predicted postoperative peak VO(2) less than 35% of predicted had an actual postoperative peak VO(2) greater than 35% of predicted (average value, 55.8%). CONCLUSIONS: The prediction of postoperative peak V̇O(2) using the segmental technique was inaccurate. The use of predicted postoperative peak VO(2) for patient selection must be cautioned against; future studies are warranted to refine its estimation.