Hormonal receptors in lung adenocarcinoma: expression and difference in outcome by sex.

BACKGROUND: Lung cancer seems to have different epidemiological, biomolecular and clinical characteristics in females than in males, with a better prognosis for women. The aim of the study is to determine gender differences in lung adenocarcinoma in terms of androgen (AR), estrogen (ER)α and progesterone (PgR) receptors expression and their impact on outcome. RESULTS: Overall survival was significantly better in ERα and in PgR positive lung adenocarcinoma patients (median survival 45 vs. 19 months).Eight out of 62 patients showed positive expression of nuclear (n) AR and 18 of cytoplasmic (c) AR with a significantly better survival (49 vs. 19 and 45 vs. 19 months, respectively). There was a significant difference in survival between patients with vs. without c-AR expression (30 vs. 17 months). Finally, in the subgroup of women, median survival was greater in positive expression of c-AR than for women with negative c-AR (45 vs. 21 months). MATERIALS AND METHODS: We conducted an analysis on a cohort of 62 patients with advanced NSCLC treated at our institution. We investigated the immunohistochemical expression of n/c AR, ERα and PgR in 62 NSCLC and we correlated it with patients' clinic-pathologic characteristics and with prognosis. CONCLUSIONS: Our results showed that the positive expression of one hormonal receptor could represent a prognostic factor.Furthermore our study suggests that AR should become object of close examination in a larger series of lung adenocarcinoma patients, also for selection of the patients with best prognosis that can perform more chemotherapy lines.

Preoperative assessment of patients for lung cancer surgery.

PURPOSE OF REVIEW: The aim of this work was to present and analyze the latest published documents about the functional evaluation of patients undergoing lung resection and review articles from the past two years addressing the same topic. RECENT FINDINGS: In 2009 and 2010, two important task forces, appointed by international scientific societies, have published documents to guide the preoperative evaluation and risk stratification of lung resection candidates. In both documents, cardiac evaluation is prioritized. Detailed cardiologic guidelines have been proposed. After this first step, functional assessment should include a spirometric assessment, asystematic measurement of carbon monoxide diffusion capacity and a cardiopulmonary exercise test evaluation. Differences in the relative importance of these tests in the two guidelines were discussed. Most recent evidences focused on the role of cardiopulmonary exercise test and the use of several direct and indirect ergometric parameters that may refine risk assessment. SUMMARY: The use of evidence-based clinical guidelines on preoperative evaluation is recommendable. Nevertheless, scientific evidence is still suboptimal in this field. Aggregate analyses on larger series are needed to improve risk stratification.

Impact of the learning curve in the use of a novel electronic chest drainage system after pulmonary lobectomy: a case-matched analysis on the duration of chest tube usage.

The objective of this investigation was to verify the impact of the learning curve involved after the introduction of a novel electronic chest drainage device on the duration of chest tube usage following pulmonary lobectomy. Propensity score case-matched analysis was used to compare the first consecutive 51 lobectomy patients managed with an electronic chest drainage (E) device with 51 controls managed with a traditional device (T). There was no difference in the characteristics of the two matched groups. Compared with patients managed with a traditional device, those with the electronic one had 1.9-day shorter duration of chest tube drainage (2.5 vs. 4.4 days; P<0.0001) and a 1.5-day shorter hospital stay (4.5 vs. 6 days; P=0.0003). Consequently, they had an average reduction in hospital costs of €751 (€1802 vs. €2553; P=0.0002). Compared with those in group T, patients in group E had a consistently shorter duration of chest tube use in relation to the very first patients treated. The learning curve sloped down for the first 40 patients before reaching a plateau, when the maximum benefit of using the electronic device was evident. Compared with traditional devices, the use of a novel electronic chest drainage system was beneficial from its initial application. The inherent learning curve was short and did not affect the efficiency of the system.

Efficacy of anterior fissureless technique for right upper lobectomies: a case-matched analysis.

OBJECTIVE: In pulmonary lobectomy, the dissection through the fissure to gain access to the pulmonary artery may increase the risk of postoperative air leak. For several anatomic reasons, this risk is especially high after right upper lobectomies (RULs). The objective of this investigation was to verify the efficacy of an anterior fissureless lobectomy (FL) technique in reducing the incidence and duration of air leak after RUL. METHODS: An observational analysis was performed of 206 consecutive patients (2002-2009) submitted to RUL for non-small-cell lung cancer. Operations were performed through a muscle-sparing lateral thoracotomy. Patients with completely developed fissures were excluded. No sealants or buttressing material were used. For group TR (traditional resection, 146 patients), RUL was performed by traditional intra-fissure dissection of the pulmonary artery; for group FL (60 patients), RUL was carried out by fissureless division of all hilar vascular structures. Several perioperative variables were used in identifying propensity score-matched pairs of patients undergoing traditional and fissureless lobectomies. The matched groups were then compared in terms of incidence of prolonged air leak, air leak duration, operation time, chest tubes duration, hospital stay and costs. RESULTS: Propensity score analysis yielded 58 well-matched pairs of patients operated by traditional or fissureless RUL. Compared to those in the traditional group, patients in group FL had a mean reduction in air leak duration, duration of chest tube and postoperative stay of 1.1, 1.4 and 1.2 days, respectively. This translated into an average hospital cost saving of 569 € per patient. CONCLUSIONS: The use of an anterior fissureless technique during RUL reduced the duration of air leak and hospital costs without increasing the surgical time. Given its simplicity and efficacy, we regard it as a useful tool for implementing fast-tracking policies and cutting hospital costs.

Prospective external convergence evaluation of two different quality-of-life instruments in lung resection patients.

OBJECTIVES: The interpretation of studies on quality of life (QoL) after lung surgery is often difficult owing to the use of multiple instruments with inconsistent scales and metrics. Although a more standardized approach would be desirable, the most appropriate instrument to be used in this setting is still largely undefined. The aim of the study was to assess the respective ability of two validated QoL instruments (European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30/L13 and Short Form (36) Health Survey (SF-36)) to detect perioperative changes in QoL of patients submitted to pulmonary resection for non-small-cell lung cancer (NSCLC). METHODS: A prospective study on 33 consecutive patients (May 2009-December 2009) was submitted to pulmonary resection. All patients completed both EORTC QLQ-C30 with lung module 13 and SF-36 pre- and postoperatively (3 months). Preoperative changes of all SF-36 and EORTC scales were assessed by using the Cohen's effect-size method. External convergence between different instruments (SF-36 vs EORTC) was assessed by measuring the correlation of scales evaluating the same concepts (physical, psychosocial, and emotional). The correlation coefficients between standardized perioperative changes (effect sizes) of objective functional parameters (forced expiratory volume in 1s (FEV1) and diffusion lung capacity for carbon monoxide (DLCO)) and SF-36 or EORTC scales were also investigated. RESULTS: A poor correlation (r < 0.5) was detected between most of the scales of the two instruments measuring the same QoL concepts, indicating that they may be complementary in investigating different aspects of QoL. Only the SF-36 and EORTC social functioning scales and the SF-36 mental health and EORTC emotional functioning scales had a correlation coefficient >0.5. In general, EORTC was more sensitive in detecting physical or emotional declines but was more conservative in detecting improvements. Both SF-36 and EORTC showed poor correlations (r < 0.5) between perioperative changes in QoL and FEV1 or DLCO, confirming that objective parameters cannot be surrogates to the subjective perception of QoL. In particular, there was a poor correlation between perceived changes in dyspnea and objective changes in FEV1 or DLCO. CONCLUSIONS: EORTC behaved similarly to SF-36 in assessing perioperative changes in generic QoL scales, but, with the use of its lung module, provided a more detailed evaluation of specific symptoms. For this reason, EORTC should be regarded as the instrument of choice for measuring QoL in the thoracic surgery setting.

Recalibration of the revised cardiac risk index in lung resection candidates.

BACKGROUND: The revised cardiac risk index (RCRI) has been proposed as a tool for cardiac risk stratification before lung resection. However, the RCRI was originally developed from a generic surgical population including a small group of thoracic patients. The objective of this study was to recalibrate the RCRI in candidates for major lung resections to provide a more specific instrument for cardiac risk stratification. METHODS: One thousand six hundred ninety-six patients who underwent lobectomy (1,426) or pneumonectomy (270) in two centers between the years of 2000 and 2008 were analyzed. Stepwise logistic regression and bootstrap analyses were used to recalibrate the six variables comprising the RCRI. The outcome variable was occurrence of major cardiac complications (cardiac arrest, complete heart block, acute myocardial infarction, pulmonary edema, or cardiac death during admission). Only those variables with a probability of less than 0.1 in more than 50% of bootstrap samples were retained in the final model and proportionally weighted according to their regression estimates. RESULTS: The incidence of major cardiac morbidity was 3.3% (57 patients). Four of the six variables present in the RCRI were reliably associated with major cardiac complications: cerebrovascular disease (1.5 points), cardiac ischemia (1.5 points), renal disease (1 point), and pneumonectomy (1.5 points). Patients were grouped into four classes according to their recalibrated RCRI, predicting an incremental risk of cardiac morbidity (p < 0.0001). Compared with the traditional RCRI, the recalibrated score had a higher discrimination (c indexes, 0.72 versus 0.62; p = 0.004). CONCLUSIONS: The recalibrated RCRI can be reliably used as a first-line screening instrument during cardiologic risk stratification for selecting those patients needing further cardiologic testing from those who can proceed with pulmonary evaluation without any further cardiac tests.

Evaluation of a new chest tube removal protocol using digital air leak monitoring after lobectomy: a prospective randomised trial.

BACKGROUND: The objective of this randomised trial was to assess the effectiveness of a new fast-track chest tube removal protocol taking advantage of digital monitoring of air leak compared to a traditional protocol using visual and subjective assessment of air leak (bubbles). METHODS: One hundred and sixty-six patients submitted to pulmonary lobectomy for lung cancer were randomised in two groups with different chest tube removal protocols: (1) in the new protocol, chest tube was removed based on digitally recorded measurements of air leak flow; (2) in the traditional protocol, the chest tube removal was based on an instantaneous assessment of air leak during daily rounds. The two groups were compared in terms of chest tube duration, hospital stay and costs. RESULTS: The two groups were well matched for several preoperative and operative variables. Compared to the traditional protocol, the new digital recording protocol showed mean reductions in chest tube duration (p=0.0007), hospital stay (p=0.007) of 0.9 day, and a mean cost saving of euro 476 per patient (p=0.008). In the new chest tube removal protocol, 51% of patients had their chest tube removed by the second postoperative day versus only 12% of those in the traditional protocol. CONCLUSIONS: The application of a chest tube removal protocol using a digital drainage unit featuring a continuous recording of air leak was safe and cost effective. Although future studies are warranted to confirm these results in other settings, the use of this new protocol is now routinely applied in our practice.

Short-term perioperative treatment with ambroxol reduces pulmonary complications and hospital costs after pulmonary lobectomy: a randomized trial.

OBJECTIVE: To assess in a randomized clinical trial the influence of perioperative short-term ambroxol administration on postoperative complications, hospital stay and costs after pulmonary lobectomy for lung cancer. METHODS: One hundred and forty consecutive patients undergoing lobectomy for lung cancer (April 2006-November 2007) were randomized in two groups. Group A (70 patients): ambroxol was administered by intravenous infusion in the context of the usual therapy on the day of operation and on the first 3 postoperative days (1000 mg/day). Group B (70 patients): fluid therapy only without ambroxol. Groups were compared in terms of occurrence of postoperative complications, length of stay and costs. RESULTS: There were no dropouts from either group and no complications related to treatment. The two groups were well matched for perioperative and operative variables. Compared to group B, group A (ambroxol) had a reduction of postoperative pulmonary complications (4 vs 13, 6% vs 19%, p=0.02), and unplanned ICU admission/readmission (1 vs 6, 1.4% vs 8.6%, p=0.1) rates. Moreover, the postoperative stay and costs were reduced by 2.5 days (5.6 vs 8.1, p=0.02) and 2765 Euro (2499 Euro vs 5264 Euro, p=0.04), respectively. CONCLUSIONS: Short-term perioperative treatment with ambroxol improved early outcome after lobectomy and may be used to implement fast-tracking policies and cut postoperative costs. Nevertheless, other independent trials are needed to verify the effect of this treatment in different settings.

Performance at symptom-limited stair-climbing test is associated with increased cardiopulmonary complications, mortality, and costs after major lung resection.

BACKGROUND: Exercise tests are increasingly used during preoperative evaluation before lung resection. This study assessed the association between performance at the symptom-limited stair-climbing test and postoperative cardiopulmonary morbidity, mortality, and costs after major lung resections. METHODS: As part of their routine preoperative evaluation, 640 patients who had lobectomy (n = 533) or pneumonectomy (n = 107) for lung cancer from January 2000 through April 2007 performed a preoperative symptom-limited stair-climbing test. Sensitivity/specificity analysis was used to identify the best cutoff values of altitude climbed (number of steps x height of the step in m) associated with outcome. Univariate and multivariate regression analyses (validated by bootstrap) were used to test associations between preoperative and operative factors and postoperative cardiopulmonary complications, mortality, and postoperative costs. RESULTS: The altitude reached at the stair-climbing test was reliably associated with increased cardiopulmonary complications (p = 0.04), mortality (p = 0.02), and costs (p < 0.0001). In patients who climbed less than 12 m, cardiopulmonary complications, mortality, and costs were 2-fold (p < 0.0001), 13-fold (p < 0.0001), and 2.5-fold higher, respectively, than in patients who climbed more than 22 m. CONCLUSIONS: Performance at a maximal stair-climbing test was reliably associated with postoperative morbidity and mortality. We recommend the use of this simple and economic test in all lung resection candidates. Patients who perform poorly at the stair-climbing test should undergo a formal cardiopulmonary exercise test with measurement of oxygen consumption to optimize their perioperative management.

Uniportal video-assisted thoracic surgery for primary spontaneous pneumothorax: clinical and economic analysis in comparison to the traditional approach.

We aimed to verify the clinical and economic effects of uniportal video-assisted thoracic surgery (VATS) in patients with primary spontaneous pneumothorax (PSP) compared to traditional three-port VATS technique. We analyzed 51 consecutive patients (23 three-port VATS and 28 uni-port VATS), treated by bullectomy and pleural abrasion, to detect differences between the two groups with regard to intraoperative management, postoperative course, pain, paraesthesia and costs. Data about pain and paraesthesia were collected by telephonic interview within a minimum follow-up period of six months. Compared to three-port VATS, patients treated by the uni-port VATS were discharged more quickly (3.8 days vs. 4.9 days, P=0.03) and experienced paraesthesia less frequently (35% vs. 94%, P<0.0001). No difference in chronic pain was observed between the two groups (numeric pain score: 0.6 uni-port vs. 1.3 three-port, P=0.2). Compared to three-port VATS, we found a significant reduction in postoperative costs for the patients operated on by the uni-port technique (euro1407 vs. euro1793, P=0.03), without any increase in surgical costs. In conclusion, uniportal VATS appears to offer better clinical (postoperative stay and rate of paraesthesia) and economic (postoperative costs) results than the standard three-port VATS for treating primary spontaneous pneumothorax.

Risk-adjusted econometric model to estimate postoperative costs: an additional instrument for monitoring performance after major lung resection.

OBJECTIVES: The objectives of this study were to develop a risk-adjusted model to estimate individual postoperative costs after major lung resection and to use it for internal economic audit. METHODS: Variable and fixed hospital costs were collected for 679 consecutive patients who underwent major lung resection from January 2000 through October 2006 at our unit. Several preoperative variables were used to develop a risk-adjusted econometric model from all patients operated on during the period 2000 through 2003 by a stepwise multiple regression analysis (validated by bootstrap). The model was then used to estimate the postoperative costs in the patients operated on during the 3 subsequent periods (years 2004, 2005, and 2006). Observed and predicted costs were then compared within each period by the Wilcoxon signed rank test. RESULTS: Multiple regression and bootstrap analysis yielded the following model predicting postoperative cost: 11,078 + 1340.3X (age > 70 years) + 1927.8X cardiac comorbidity - 95X ppoFEV1%. No differences between predicted and observed costs were noted in the first 2 periods analyzed (year 2004, $6188.40 vs $6241.40, P = .3; year 2005, $6308.60 vs $6483.60, P = .4), whereas in the most recent period (2006) observed costs were significantly lower than the predicted ones ($3457.30 vs $6162.70, P < .0001). CONCLUSIONS: Greater precision in predicting outcome and costs after therapy may assist clinicians in the optimization of clinical pathways and allocation of resources. Our economic model may be used as a methodologic template for economic audit in our specialty and complement more traditional outcome measures in the assessment of performance.

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.

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.