Eric M. Toloza

Thoracoscopic Lobectomy Is a Safe and Versatile Procedure: Experience With 500 Consecutive Patients

Objective:Advantages of thoracoscopic lobectomy for early stage non-small cell lung cancer (NSCLC), as compared with lobectomy by conventional thoracotomy, include less postoperative pain and shorter length of hospitalization. The outcomes after thoracoscopic lobectomy in patients with more complex pulmonary conditions are analyzed to determine safety, efficacy, and versatility. Methods:A prospective database of 500 consecutive patients who underwent thoracoscopic lobectomy between June 1999 and January 2006 was queried. Demographic, histopathologic, perioperative, and outcome variables were assessed using standard descriptive statistics and Kaplan-Meier survival analyses. Results:Thoracoscopic lobectomy was successfully performed in 492 patients (conversion rate, 1.6%). Pathologic analysis included primary NSCLC in 416 patients (83.2%), centrally located secondary pulmonary malignancy in 37 patients (7.4%), and a variety of benign conditions in 45 patients (9%). Among the 416 patients with NSCLC, pathologic analysis demonstrated stage I in 330 patients (55.3%), stage II in 40 patients (9.6%), and stage III or greater NSCLC in 44 patients (10.6%). The operative and perioperative (30-day) mortality was 0% and 1%, respectively. The overall 2-year survival rate for the entire cohort was 80%, and the 2-year overall survival rates for stage I NSCLC, stage II or greater NSCLC, secondary pulmonary malignancy, and granulomatous disease patients were 85%, 77%, 73%, and 89%, respectively. Conclusions:Thoracoscopic lobectomy is applicable to a spectrum of malignant and benign pulmonary disease and is associated with a low perioperative morbidity and mortality rate. Survival rates are comparable to those for lobectomy with thoracotomy.

Thoracoscopic lobectomy is associated with lower morbidity compared with thoracotomy

OBJECTIVESnAdvantages of thoracoscopic lobectomy include less postoperative pain, shorter hospitalization, and improved delivery of adjuvant chemotherapy. The incidence of postoperative complications has not been thoroughly assessed. This study analyzes morbidity after lobectomy to compare the thoracoscopic approach and thoracotomy.nnnMETHODSnBy using a prospective database, the outcomes of patients who underwent lobectomy from 1999-2009 were analyzed with respect to postoperative complications. Propensity-matched groups were analyzed based on preoperative variables and stage.nnnRESULTSnOf the 1079 patients in the study, 697 underwent thoracoscopic lobectomy, and 382 underwent lobectomy by means of thoracotomy. In the overall analysis thoracoscopic lobectomy was associated with a lower incidence of atrial fibrillation (P = .01), atelectasis (P = .0001), prolonged air leak (P = .0004), transfusion (P = .0001), pneumonia (P = .001), sepsis (P = .008), renal failure (P = .003), and death (P = .003). In the propensity-matched analysis based on preoperative variables, when comparing 284 patients in each group, 196 (69%) patients who underwent thoracoscopic lobectomy had no complications versus 144 (51%) patients who underwent thoracotomy (P = .0001). In addition, thoracoscopic lobectomy was associated with a lower incidence of atrial fibrillation (13% vs 21%, P = .01), less atelectasis (5% vs 12%, P = .006), fewer prolonged air leaks (13% vs 19%, P = .05), fewer transfusions (4% vs 13%, P = .002), less pneumonia (5% vs 10%, P = .05), less renal failure (1.4% vs 5%, P = .02), shorter chest tube duration (median of 3 vs 4 days, P < .0001), and shorter length of hospital stay (median of 4 vs 5 days, P < .0001).nnnCONCLUSIONSnThoracoscopic lobectomy is associated with a lower incidence of major complications, including atrial fibrillation, compared with lobectomy by means of thoracotomy. The underlying factors responsible for this advantage should be analyzed to improve the safety and outcomes of other thoracic procedures.

Chronic LPS Inhalation Causes Emphysema-Like Changes in Mouse Lung that Are Associated with Apoptosis

Lipopolysaccharide (LPS) is ubiquitous in the environment. Recent epidemiologic data suggest that occupational exposure to inhaled LPS can contribute to the progression of chronic obstructive pulmonary disease. To address the hypothesis that inhaled LPS can cause emphysema-like changes in mouse pulmonary parenchyma, we exposed C57BL/6 mice to aerosolized LPS daily for 4 weeks. By 3 days after the end of the 4-week exposure, LPS-exposed mice developed enlarged airspaces that persisted in the 4-week recovered mice. These architectural alterations in the lung are associated with enhanced type I, III, and IV procollagen mRNA as well as elevated levels of matrix metalloproteinase (MMP)-9 mRNA, all of which have been previously associated with human emphysema. Interestingly, MMP-9-deficient mice were not protected from the development of LPS-induced emphysema. However, we demonstrate that LPS-induced airspace enlargement was associated with apoptosis within the lung parenchyma, as shown by prominent TUNEL staining and elevated cleaved caspase 3 immunoreactivity. Antineutrophil antiserum-treated mice were partially protected from the lung destruction caused by chronic inhalation of LPS. Taken together, these findings demonstrate that inhaled LPS can cause neutrophil-dependent emphysematous changes in lung architecture that are associated with apoptosis and that these changes may be occurring through mechanisms different than those induced by cigarette smoke.

Outcomes of Video-Assisted Thoracoscopic Decortication

BACKGROUNDnVideo-assisted thoracoscopic surgical decortication (VATSD) is widely used for treatment of early empyema and hemothorax, but conversion to open thoracotomy for decortication (OD) is more frequent in the setting of complex, chronic empyema. This study compared indications for and outcomes associated with VATSD and OD.nnnMETHODSnThe outcomes of 420 consecutive patients undergoing VATSD or OD for benign conditions from 1996 to 2006 were reviewed and compared with respect to baseline characteristics, preoperative management, and operative and postoperative course. Patients were analyzed on an intention-to-treat basis.nnnRESULTSnThe cohort consisted of 326 VATSD and 94 OD patients. The conversion rate from VATSD to OD was 11.4%. The operative time and median in-hospital length of stay were shorter for the VATSD group: 97 vs 155 minutes (p < 0.001), and 15 vs 21 days (p = 0.03), respectively. The median postoperative length of stay was 7 days for the VATSD group vs 10 days for the OD group (p < 0.001). Significantly fewer postoperative complications occurred in the VATSD group in the following categories: atelectasis, prolonged air leak, reintubation, ventilator dependence, need for tracheostomy, blood transfusion, sepsis, and 30-day mortality.nnnCONCLUSIONSnThoracoscopic decortication for empyema, complex pleural effusion, and hemothorax yields results that are at least equivalent to open decortication. Patients undergoing VATSD have fewer postoperative complications. The conversion and reoperation rates are low, suggesting that a thoracoscopic approach is an effective and reasonable first option for most patients with complex pleural effusions and empyema.

Quality of life outcomes are equivalent after lobectomy in the elderly

OBJECTIVEnProspective analyses of quality of life in elderly patients after lobectomy are limited, yet surgeons often recommend suboptimal therapy to these patients on the basis of the belief that lobectomy is poorly tolerated. Surgical decision making in elderly patients with lung cancer is better informed when the benefits to survival and quality of life after lobectomy are understood.nnnMETHODSnBy using a validated quality of life instrument, 422 patients were prospectively assessed preoperatively and 3, 6, and 12 months after lobectomy. Outcomes were analyzed with respect to age (group 1: < 70 years and group 2: > or = 70 years). The outcome domains of physical functioning, role functioning, emotional functioning, cognitive functioning, social functioning, global health, and pain in the chest were analyzed using a mixed model. The trend in quality of life was determined according to age. The Kaplan-Meier method was used for analysis of overall survival.nnnRESULTSnThe mean age was 60.1 years in group 1 (N = 256) and 74.7 years in group 2 (N = 166). Baseline demographics and quality of life were similar except that group 2 had better emotional functioning scores and worse pain in the chest scores. Postoperatively, both groups demonstrated significant decreases in quality of life at 3 months. However, at 6 and 12 months, all domains had returned to baseline except physical functioning, which remained below baseline in group 2. Emotional functioning improved postoperatively for both groups. Overall survival at 5 years was not different between groups.nnnCONCLUSIONnBy using a validated quality of life assessment tool with measurements at baseline and serially after resection in a large patient population, this analysis quantifies the degree of impairment of quality of life after lobectomy and documents time to full recovery for both age groups.

Impact of a multidisciplinary thoracic oncology clinic on the timeliness of care.

Background: Multidisciplinary clinics have been recommended for the evaluation of patients with lung cancer. Evidence to support this recommendation, however, is limited. A single-center, retrospective review of lung cancer patients at a Veterans Affairs hospital was performed comparing timeliness of diagnostic and treatment decisions during the operation of a multidisciplinary thoracic oncology clinic (MTOC) with a period after it closed (non-MTOC), during which only a weekly multidisciplinary conference was held. Methods: Patients were identified from a tumor registry. Manual chart reviews were performed on all patients. Outcome measures included time from initial presentation to diagnosis (TTD) and time from diagnosis to treatment initiation (TTT). Results: Three hundred forty-five patients (244 in MTOC, 101 in non-MTOC) diagnosed with lung cancer between 1999 and 2003 were included in the study. Baseline characteristics were similar between the two groups. Median TTD was 48 days (95% confidence interval [CI]: 37–61) and 47 days (95% CI: 39–55) in the MTOC (n = 164) and non-MTOC cohorts (n = 89), respectively (p = 0.09). Median TTT was 22 days (95% CI: 20–27) and 23 days (95% CI: 20–34) in the MTOC (n = 165) and non-MTOC cohorts (n = 89), respectively (p = 0.71). There was no difference in overall survival. Conclusion: Retrospective comparison of sequential cohorts failed to reveal benefit in the timeliness of care measures during the time period of MTOC operation. Potential confounders include the absence of a surgeon in the MTOC setting, an ongoing weekly multidisciplinary conference in the non-MTOC cohort, and existing infrastructures based on previous MTOC experiences and past provider experience. Confirmation of these findings in other health care settings is warranted, preferably in a prospective fashion.

A cost-minimisation analysis of lobectomy: thoracoscopic versus posterolateral thoracotomy.

OBJECTIVEnRecent evidence suggests that lobectomy performed either through thoracoscopy (TL) or via a posterolateral thoracotomy (PLT) produces equivalent oncologic outcomes in appropriately selected patients. Advantages of thoracoscopic lobectomy include decreased postoperative pain, shorter length of stay, fewer postoperative complications and better compliance with adjuvant chemotherapy. This study evaluates the costs associated with lobectomy performed thoracoscopically or via thoracotomy.nnnMETHODSnThis is a retrospective analysis of actual costing and prospectively collected health-related quality of life (QOL) outcomes. Between 2002 and 2004, 113 patients underwent lobectomy (PLT: n=37; TL: n=76) and completed QOL assessments both preoperatively and 1-year postoperatively. Actual fixed and variable direct costs from the preoperative, hospitalisation and 30-day postoperative phases were captured using a T1 cost accounting system and were combined with actual professional collections. Cost-utility analysis was performed by transforming a global QOL measurement to an estimate of utility and calculating a quality-adjusted life year (QALY) for each patient.nnnRESULTSnBaseline characteristics were similar in the two groups. Total costs (USD) were significantly greater for the strategy of PLT (USD 12,119) than for TL (USD 10,084; p=0.0012). Even when only stage I and II lung cancers were included (n=32 PLT, n=69 TL), total costs for PLT were still higher than that for TL (USD 11,998 vs USD 10,120; p=0.005). The mean QALY for the PLT group was 0.74+/-0.22 and for the TL group was 0.72+/-0.18 (p=0.68).nnnCONCLUSIONSnIn this retrospective analysis, TL was significantly less expensive than PLT from the preoperative evaluation through 30 days postoperatively, with overall savings of approximately USD 2000 per patient. In light of equivalent QALY outcomes, this cost-utility analysis supports increased adoption of TL as a cost-minimisation strategy. The use of TL for the 50,000 lobectomies performed in the United States each year would represent a savings of approximately USD 100 million.

The Role of Intrathoracic Free Flaps for Chronic Empyema

BACKGROUNDnThe management of chronic empyema associated with a bronchopleural fistula can be a particularly challenging problem. Successful eradication may not occur without interposition of healthy vascularized tissue. Pedicled muscle flaps for coverage on the thorax have been well described. However, secondary to trauma or previous surgical procedures, a pedicle flap may not be sufficiently sized or available. Free tissue transfer is an attractive option to provide the appropriate vascularized tissue.nnnMETHODSnSix patients with chronic empyema-bronchopleural fistulae were reconstructed with 4 rectus abdominis myocutaneous and 2 gracilis muscle flaps. The choice of recipient vessels was dictated by existing local anatomy but included intercostal, thoracodorsal, thoracoacromial, azygous, and circumflex humeral vessels. One flap required interposition saphenous vein grafts for both artery and vein.nnnRESULTSnPatient follow-up ranged from 2 to 14 years. There were no episodes of flap loss or postoperative mortality. Empyema resolution without recurrent bronchopleural fistula was achieved in all patients.nnnCONCLUSIONSnFree tissue transfer is an excellent option for vascularized tissue interposition in patients who are not candidates for pedicled muscle transfer. Multiple potential recipient vessels provide tremendous versatility, arguing for early consideration of free tissue transfer.

Intraoperative techniques to prevent air leaks

Persistent air leaks prolong chest tube duration and hospital stay after lung surgery. Air leaks also may lead to life-threatening empyemas. Preventing postoperative air leaks and BPFs is the best treatment for air-leak complications. Meticulous closure of parenchymal, pleural, and bronchial defects is the mainstay of air-leak control. The reinforcement of parenchymal suture and staple lines, pleural apposition, and well-vascularized tissue-flap coverage of bronchial suture and staple lines further reduce the incidence of prolonged air leaks and BPFs.

Gene therapy for lung cancer.

Lung cancer patients suffer a 15% overall survival despite advances in chemotherapy, radiation therapy, and surgery. This unacceptably low survival rate is due to the usual finding of advanced disease at diagnosis. However, multimodality strategies using conventional therapies only minimally improve survival rates even in early stages of lung cancer. Attempts to improve survival in advanced disease using various combinations of platinum‐based chemotherapy have demonstrated that no regimen is superior, suggesting a therapeutic plateau and the need for novel, more specific, and less toxic therapeutic strategies. Over the past three decades, the genetic etiology of cancer has been gradually delineated, albeit not yet completely. Understanding the molecular events that occur during the multistep process of bronchogenic carcinogenesis may make these tasks more surmountable. During these same three decades, techniques have been developed which allow transfer of functional genes into mammalian cells. For example, blockade of activated tumor‐promoting oncogenes or replacement of inactivated tumor‐suppressing or apoptosis‐promoting genes can be achieved by gene therapy. This article will discuss the therapeutic implications of these molecular changes associated with bronchogenic carcinomas and will then review the status of gene therapies for treatment of lung cancer. J. Cell. Biochem.