Reflux control is important in the management of Barrett's Esophagus: results from a retrospective 1,830 patient cohort.

BACKGROUND: It is unknown whether acid/reflux control prevents progression in Barrett's esophagus. In this study, we investigate whether medical or surgical control of reflux is associated with a decreased risk of progression to dysplasia/esophageal adenocarcinoma. METHODS: We retrospectively collected and analyzed data from a cohort of Barrett's esophagus patients participating in this single-center study comprised of all patients diagnosed with Barrett's esophagus at NorthShore University Health System hospitals and clinics over a 10-year period. Patients were followed in order to identify those progressing from Barrett's esophagus to low-grade dysplasia, high-grade dysplasia, and esophageal adenocarcinoma. We collected information from the patient's electronic medical records regarding demographic, endoscopic findings, histological findings, smoking/alcohol history, medication use including proton-pump inhibitors, and history of bariatric and antireflux surgery. Risk-adjusted modeling was performed using multivariable logistic regression. RESULTS: This study included 1,830 total Barrett's esophagus patients, 102 of which had their Barrett's esophagus progress to low-grade dysplasia, high-grade dysplasia, or esophageal adenocarcinoma (confirmed by biopsy) with an annual incidence rate of 1.1%. Mean follow-up period was 5.51 years (10,083 patient-years). Compared to the group that did not progress, the group that progressed was older (69.3 ± 13.7 vs. 63.9 ± 13.4 years. p < 0.001) and likely to be male (75 vs. 61%, p < 0.01). In the multivariable analysis, patients who had a history of antireflux surgery (n = 44) or proton-pump inhibitor use without surgery (n = 1,641) were found to progress at significantly lower rates than patients who did not have antireflux surgery or were not taking PPI's (OR 0.18, 95% CI 0.09-0.36). CONCLUSIONS: Reflux control was associated with decreased risk of progression to low-grade dysplasia, high-grade dysplasia, or esophageal adenocarcinoma. These results support the use of reflux control strategies such as proton-pump inhibitor therapy or surgery in patients with non-dysplastic Barrett's esophagus for the prevention of progression to dysplasia/adenocarcinoma.

Predicting regression of Barrett's esophagus: results from a retrospective cohort of 1342 patients.

INTRODUCTION: Barrett's esophagus (BE) is the most predictive risk factor for development of esophageal adenocarcinoma (EAC), a malignancy with the fastest increasing incidence in the US. The aim of this study was to investigate differences in exposures, demographics, and comorbidities between regressing and non-regressing patients. METHODS AND PROCEDURES: We retrospectively collected and analyzed data from a cohort of BE patients participating in a single-center study comprised of all patients diagnosed with BE over a 10-year period. We collected information from the patient's electronic medical records regarding demographic data, endoscopic findings, histological findings, exposures, and history of antireflux surgery. RESULTS: This study included 1,342 BE patients, 505 (37.6%) of which experienced regression. The regressed group was 52.3% male, while the non-regressing group was 68.3% male (p < 0.001). Mean age was 65.2 ± 12.8 and 62.0 ± 13.1 years for non-regressing and regressing patients, respectively (p < 0.001). No difference was seen in BMI between regressing and non-regressing groups (27.5 ± 5.7 vs. 27.7 ± 5.4, p = 0.52). No difference was seen between groups with respect to PPI use (93.5% non-regressing vs. 94.1% regressed patients, p = 0.70), but regressed patients were more likely to take vitamin D than non-regressing patients (34.1 vs. 42.1%, p = 0.003). Regressed patients had an average segment length of 1.48 cm (±1.58 cm), in contrast to those not regressing (3.58 ± 3.09 cm (p < 0.001)). Interestingly, one patient in the regression group progressed to dysplasia, while 101 of the non-regressing patients progressed to dysplasia/EAC, a result found to be independent of segment length on multivariate analysis (p < 0.001). CONCLUSIONS: Currently, several studies have shown risk factors that can predict progression of non-dysplastic BE, but few investigate predictors for regression. Our study reports several factors that can be used to predict patients who will regress from BE and those who likely will not, tools that will be useful in tailoring therapeutic and surveillance strategies.

Efficacy of intrapleural tissue-type plasminogen activator in the treatment of loculated parapneumonic effusions.

PURPOSE: To assess the feasibility and effectiveness of intrapleural recombinant tissue-type plasminogen activator (r-tPA) in the treatment of loculated parapneumonic effusions (PPEs). MATERIALS AND METHODS: A single-arm prospective study of 25 consecutive patients with loculated PPEs was analyzed. All patients received 6-mg doses of intrapleural r-tPA on a defined schedule via a thoracostomy tube. The volume of output from the tubes was recorded and analysis of the fluid composition performed. Follow-up was both clinical and radiographic, with all patients undergoing pre- and postprocedural computed tomography. RESULTS: Eighteen of the 25 patients (72%) required no additional intervention and had a complete clinical and radiographic response with the fibrinolytic therapy. Seven patients (28%) were treated with video-assisted thoracoscopic surgery, but no patient required thoracotomy for total decortication. There were no hemorrhagic complications. CONCLUSIONS: Intrapleural r-tPA is effective in the treatment of loculated PPEs. It can be performed safely and in some patients may avoid the need for additional surgical intervention.

Neoadjuvant Chemoradiation Shows No Survival Advantage to Chemotherapy Alone in Stage IIIA Patients.

BACKGROUND: For operable patients with clinical stage IIIA non-small cell lung cancer, the optimum neoadjuvant treatment strategy remains unclear. Our aim was to compare perioperative and long-term outcomes for patients receiving neoadjuvant chemoradiotherapy (NCRT) versus neoadjuvant chemotherapy (NCT) alone. METHODS: We queried the National Cancer Database to identify all patients with N2 and either T1-T2 non-small cell lung cancer who received either NCRT or NCT followed by lobectomy between 2006 and 2012. Patients with T3 tumors were excluded. A propensity match analysis was performed incorporating preoperative variables, and the incidence of postoperative complications, pathologic downstaging, and long-term survival were compared. RESULTS: In all, 1,936 patients met criteria, 745 NCT and 1,191 NCRT. The NCRT patients were younger, less likely to be treated at an academic medical center, and more likely to have adenocarcinoma. After propensity matching, patients in the NCT group showed lower 30-day mortality (1.3% versus 2.9%) and 90-day mortality (2.9% versus 6.0%), and were more likely to undergo a minimally invasive resection (25.7% versus 14.1%). The NCRT patients were more likely to have a pathologic complete response (14.2% versus 4.0%) and to be N0 at the time of resection (45.2% versus 38.7%). In the multivariable analysis, NCRT patients were at a greater risk of mortality than NCT patients (hazard ratio 1.18, 95% confidence interval: 1.03 to 1.36). CONCLUSIONS: In our cohort, combined neoadjuvant chemotherapy and radiation therapy was associated with improved pathologic downstaging but showed increased perioperative mortality with no improvement in long-term overall survival. For stage IIIA patients with smaller tumors without local invasion, chemotherapy alone may be the preferred neoadjuvant treatment.

Surgical quality of wedge resection affects overall survival in patients with early stage non-small cell lung cancer.

OBJECTIVES: Very few studies have examined the quality of wedge resection in patients with non-small cell lung cancer. Using the National Cancer Database, we evaluated whether the quality of wedge resection affects overall survival in patients with early disease and how these outcomes compare with those of patients who receive stereotactic radiation. METHODS: We identified 14,328 patients with cT1 to T2, N0, M0 disease treated with wedge resection (n = 10,032) or stereotactic radiation (n = 4296) from 2005 to 2013 and developed a subsample of propensity-matched wedge and radiation patients. Wedge quality was grouped as high (negative margins, >5 nodes), average (negative margins, ≤5 nodes), and poor (positive margins). Overall survival was compared between patients who received wedge resection of different quality and those who received radiation, adjusting for demographic and clinical variables. RESULTS: Among patients who underwent wedge resection, 94.6% had negative margins, 44.3% had 0 nodes examined, 17.1% had >5 examined, and 3.0% were nodally upstaged; 16.7% received a high-quality wedge, which was associated with a lower risk of death compared with average-quality resection (adjusted hazard ratio [aHR], 0.74; 95% confidence interval [CI], 0.67-0.82). Compared with stereotactic radiation, wedge patients with negative margins had significantly reduced hazard of death (>5 nodes: aHR, 0.50; 95% CI, 0.43-0.58; ≤5 nodes: aHR, 0.65; 95% CI, 0.60-0.70). There was no significant survival difference between margin-positive wedge and radiation. CONCLUSIONS: Lymph nodes examined and margins obtained are important quality metrics in wedge resection. A high-quality wedge appears to confer a significant survival advantage over lower-quality wedge and stereotactic radiation. A margin-positive wedge appears to offer no benefit compared with radiation.

Predictors of pathologic upstaging in early esophageal adenocarcinoma: Results from the national cancer database.

BACKGROUND: Upstaging in early esophageal adenocarcinoma (EAC) patients happens at a high rate and has implications for treatment. We sought to identify risk factors predicting upstaging. STUDY DESIGN: The National Cancer Database (2010-2013) was queried for all patients with clinical T1/T2 and N0 EAC who underwent esophagectomy without neoadjuvant therapy. Logistic regression models were developed to investigate risk factors for upstaging. RESULTS: A total of 1120 patients were included. Pathologic upstaging occurred in 21.3% (n = 239). After adjustment, risk of upstaging increased with tumor size (tumor size 1-3 cm, OR 4.57,95% CI 2.58-8.10, tumor size >3 cm, OR 10.57, 95% CI 5.77-19.35, as compared to tumors <1 cm) as well as with positive margins (OR 4.13, 95% CI 2.17-7.87) and > than 10 lymph nodes examined (OR 1.85, 95% CI 1.29-2.63), while facility volume was not significant. Odds of upstaging increased linearly with number of lymph nodes examined (OR 1.02 per node). CONCLUSION: Our data underscore the importance of tumor size as a predictor for upstaging and of completing a thorough lymph node dissection for staging purposes.

Invasive Mediastinal Staging for Lung Cancer by The Society of Thoracic Surgeons Database Participants.

BACKGROUND: Prior studies suggest underutilization of invasive mediastinal staging for lung cancer. We hypothesized that The Society of Thoracic Surgeons General Thoracic Surgery Database (STS-GTSD) participants would have higher rates of invasive staging compared with previous reports. METHODS: We conducted a retrospective cohort study (2012 to 2016) of lung cancer patients staged by computed tomography and positron-emission tomography and first treated with an anatomic resection. We defined invasive staging by the use of mediastinoscopy, endosonography, or thoracoscopy. Standardized incidence ratios were used to compare participant-level rates of invasive staging, and Poisson regression was used to identify factors associated with invasive staging. RESULTS: Among 29,015 patients across 256 participating STS-GTSD sites, 34% (95% confidence interval: 33% to 34%) underwent invasive staging. The overall rate of invasive staging did not change between 2012 and 2016 (p trend = 0.16). Increasing clinical stage and features suggestive of a central tumor were associated with invasive staging (p < 0.001). Rates of invasive staging among patients with clinical stage IB or greater or features suggestive of a central tumor were 43% (95% confidence interval: 42% to 44%) and 52% (95% confidence interval: 50% to 54%), respectively. There was a more than 40-fold variation in rates of invasive staging across 251 centers contributing at least 10 cases (standardized incidence ratio: lowest = 0.08; highest = 3.26); 66 sites (26%) performed invasive mediastinal staging less often than average and 77 sites (31%) performed invasive staging more often than average. CONCLUSIONS: The STS-GTSD participants performed invasive mediastinal staging more frequently than prior reports, and yet only in a minority of patients. Rates of invasive mediastinal staging vary widely across STS-GTSD participants.

Preliminary report of a prospective, randomized trial of underwater seal for spontaneous and iatrogenic pneumothorax.

BACKGROUND: Management of pneumothorax has traditionally been tube thoracostomy and -20 cm H2O suction. The purpose of our study was to determine if underwater seal in iatrogenic and spontaneous pneumothoraces is safe and efficacious and if small-caliber chest tubes are appropriate for routine use in pneumothorax. STUDY DESIGN: From April 2001 through October 2003 patients with iatrogenic or spontaneous pneumothorax were enrolled in this prospective, randomized trial. Small-bore catheters were inserted. Initial management was 1 hour -20 cm H2O suction, chest radiography, and randomization into -20 cm H2O suction, -10 cm H2O suction, or underwater seal. Tubes were discontinued at 48 hours if there were no pneumothoraces and no air leaks. Those with air leaks and recurrent pneumothoraces persisting 5 days underwent pleurodesis. The primary end point was successful chest tube removal at 48 hours. The secondary end point was need for pleurodesis. RESULTS: Twenty-nine patients were analyzed. Seven were randomized to -20 cm H2O suction, 11 to -10 cm H2O suction, and 11 to underwater seal. Most (59%, 17 of 29) chest tubes were successfully removed 48 hours after placement: 57% (4 of 7) after -20 cm H2O suction, 73% (8 of 11) after -10 cm H2O suction, and 45% (5 of 11) after underwater seal (p = 0.48). Seven (24%) required pleurodesis: 29% (2 of 7) after -20 cm H2O suction, 27% (3 of 11) after -10 cm H2O suction, and 18% (2 of 11) after underwater seal (p = 0.70). CONCLUSIONS: Early underwater seal appears to be safe for treating iatrogenic and spontaneous pneumothoraces. It can achieve comparable frequencies of early chest tube removal and avoidance of operation compared with traditional management. A larger, multi-institutional study should be performed to demonstrate that pneumothorax treatment can effectively incorporate small-caliber tubes and underwater seal.

The role of VATS for staging and diagnosis in patients with non-small cell lung cancer.

Video-assisted thoracoscopic surgery is an effective and versatile tool for the diagnosis and staging of patients with lung cancer. Despite advances in imaging technology, including integrated positron emission tomography/computed tomography scans, the clinical staging of patients with lung cancer remains inaccurate. Tissue confirmation is critical for accurate staging and treatment of patients with lung cancer. Thoracoscopy is an excellent and often preferred approach to the biopsy of inferior mediastinal, anteroposterior window, and para-aortic lymph nodes, and has the added advantage of allowing simultaneous assessment of the pleural space, satellite lung nodules, and T status of the tumor. Thoracoscopic wedge resection is the preferred technique for diagnosing indeterminate solitary pulmonary nodules. In the era of computed tomography screening, most indeterminate lung nodules are less than 1 cm in size and pose unique challenges in determining malignant potential and obtaining a tissue diagnosis. Several techniques have been adopted to allow successful thoracoscopic biopsy of these subcentimeter lung nodules.

Minimally Invasive Esophagectomy Provides Equivalent Survival to Open Esophagectomy: An Analysis of the National Cancer Database.

The use of minimally invasive esophagectomy (MIE) is increasing despite limited evidence to support its efficacy. We compared overall survival and perioperative mortality for MIE vs open esophagectomy (OE). We queried the National Cancer Database for all patients having esophagectomy as the primary procedure for primary squamous cell cancer and adenocarcinoma from 2010 through 2012. A propensity score analysis was performed. Postoperative pathology and quality, as well as overall patient survival outcomes, were compared between OE and MIE. The use of MIE increased from 26.9% in 2010 to 36.3% in 2012 (P < 0.001). Of 3032 patients (2050 OE and 982 MIE) who were identified, propensity score matching (1:1) yielded 977 patients in each group. Mean lymph nodes examined were higher in the MIE group (16.3 vs 14.5, P < 0.001). However, final pathologic nodal stage was not significantly different in the matched sample. There was also no difference in pathologic upstaging or margin status between the groups. All other postoperative variables were equivalent, including an average length of stay of 14 days, unplanned readmission rate of 6.5%, and 30-day and 90-day mortality rates of 3% and 7%, respectively. There was no survival difference, with a median survival of 48.7 months for OE and 46.6 months for MIE (Kaplan-Meier analysis, P = 0.376). During the 3-year period analyzed, there were no significant differences in postoperative outcomes and quality metrics between OE and MIE. Although short-term outcomes are limited in the National Cancer Database, MIE appears to have equivalent oncological outcomes and survival when compared with the open approach.

Improved Lymph Node Staging in Early-Stage Lung Cancer in the National Cancer Database.

BACKGROUND: Lymph node assessment for non-small cell lung cancer (NSCLC) shows wide variation among centers. Our aim was to assess the quality of lymph node assessment in early-stage NSCLC and determine whether any factors are associated with improved lymph node harvest. METHODS: We queried the National Cancer Database to identify patients with clinical stage I NSCLC who underwent segmentectomy or lobectomy between 2004 and 2013. Patients were stratified into three groups (≤5, 6 to 15, and >15) based on the number of lymph nodes assessed. RESULTS: Patients (n = 51,358) met criteria, and mean lymph nodes assessed increased from 8.1 to 10.0 (p < 0.001) over the study period. There was a significant decrease in the percentage of patients with 0 to 5 nodes assessed (41.1% versus 31.1%, p < 0.001) and a significant increase in patients with more than 15 nodes assessed (10.1% versus 17.0%, p < 0.001). Patients at academic centers were less likely to have only 0 to 5 nodes assessed (27.2% versus 43.6% for community, p < 0.001). Variables associated with more than 15 nodes assessed were increasing year, age older than 65 years, male sex, non-African American race, academic centers, lobectomy, and clinical T2 disease. Patients with more than 14 nodes assessed demonstrated more nodal upstaging (17.9% versus 10.9% for 1 to 14 nodes, p < 0.001). Multivariable analysis suggests that at least 14 nodes should be assessed to maximize the probability that node-positive patients are correctly identified. CONCLUSIONS: Lymph node assessment has improved since 2004 but varies by facility type and other characteristics. In our analysis removing at least 14 nodes was associated with more accurate staging.

Survival after resection for lung cancer is the outcome that matters.

BACKGROUND: Lung cancer is the leading cause of cancer mortality in the United States. Stage-specific survival is well documented in national data sets; however, there remains limited recording of longitudinal survival in individual centers. METHODS: The VistA Surgery Package was employed to list operations performed by the thoracic surgery service at one Veterans Administration (VA) Medical Center. RESULTS: During a period of 107 months, 416 thoracic operations were performed, 211 of them for lung cancer. Stage distribution was 66% stage I, 18% stage II, 12% stage III, and 4% stage IV. During follow-up, 102 patients died, 57 of them from disease-specific causes. Median survival was 39 months for stage I. Disease-specific median survival was 83 months for stage I, and 5-year survival was 52% (72% for stage IA and 32% for stage IB). CONCLUSIONS: Pulmonary resection offers high disease-free survival for early-stage lung cancer. Decentralized hospital computer programming (DHCP) allows individual oncology programs to reliably measure survival. Use of this important outcome measure in quality improvement programs facilitates realistic counseling of patients and meaningful assessments of practice effectiveness.

Treatment of stage I and II non-small cell lung cancer: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines.

BACKGROUND: The treatment of stage I and II non-small cell lung cancer (NSCLC) in patients with good or low surgical risk is primarily surgical resection. However, this area is undergoing many changes. With a greater prevalence of CT imaging, many lung cancers are being found that are small or constitute primarily ground-glass opacities. Treatment such as sublobar resection and nonsurgical approaches such as stereotactic body radiotherapy (SBRT) are being explored. With the advent of minimally invasive resections, the criteria to classify a patient as too ill to undergo an anatomic lung resection are being redefined. METHODS: The writing panel selected topics for review based on clinical relevance to treatment of early-stage lung cancer and the amount and quality of data available for analysis and relative controversy on best approaches in stage I and II NSCLC: general surgical care vs specialist care; sublobar vs lobar surgical approaches to stage I lung cancer; video-assisted thoracic surgery vs open resection; mediastinal lymph node sampling vs lymphadenectomy at the time of surgical resection; the use of radiation therapy, with a focus on SBRT, for primary treatment of early-stage NSCLC in high-risk or medically inoperable patients as well as adjuvant radiation therapy in the sublobar and lobar resection settings; adjuvant chemotherapy for early-stage NSCLC; and the impact of ethnicity, geography, and socioeconomic status on lung cancer survival. Recommendations by the writing committee were based on an evidence-based review of the literature and in accordance with the approach described by the Guidelines Oversight Committee of the American College of Chest Physicians. RESULTS: Surgical resection remains the primary and preferred approach to the treatment of stage I and II NSCLC. Lobectomy or greater resection remains the preferred approach to T1b and larger tumors. The use of sublobar resection for T1a tumors and the application of adjuvant radiation therapy in this group are being actively studied in large clinical trials. Every patient should have systematic mediastinal lymph node sampling at the time of curative intent surgical resection, and mediastinal lymphadenectomy can be performed without increased morbidity. Perioperative morbidity and mortality are reduced and long-term survival is improved when surgical resection is performed by a board-certified thoracic surgeon. The use of adjuvant chemotherapy for stage II NSCLC is recommended and has shown benefit. The use of adjuvant radiation or chemotherapy for stage I NSCLC is of unproven benefit. Primary radiation therapy remains the primary curative intent approach for patients who refuse surgical resection or are determined by a multidisciplinary team to be inoperable. There is growing evidence that SBRT provides greater local control than standard radiation therapy for high-risk and medically inoperable patients with NSCLC. The role of ablative therapies in the treatment of high-risk patients with stage I NSCLC is evolving. Radiofrequency ablation, the most studied of the ablative modalities, has been used effectively in medically inoperable patients with small (< 3 cm) peripheral NSCLC that are clinical stage I.

In-hospital clinical and economic consequences of pulmonary wedge resections for cancer using video-assisted thoracoscopic techniques vs traditional open resections: a retrospective database analysis.

OBJECTIVE: The objective of this study was to compare the safety, use, and cost profiles of open thoracotomy vs video-assisted thoracoscopic surgery (VATS) for wedge resection in lung cancer performed by thoracic surgeons in the United States. METHODS: The Premier database, which contains complete patient billing, hospital cost, and coding histories from > 25 million inpatient discharges and > 175 million hospital outpatient visits, was used for this analysis. Eligible patients were those who underwent wedge resection by a thoracic surgeon for cancer diagnosis or treatment through open thoracotomy or VATS in 2007 or 2008. Multivariable logistic regression analyses were run for binary outcomes, and ordinary least squares regressions were used for continuous outcomes. All models were adjusted for patient demographics, comorbid conditions, and hospital characteristics. RESULTS: Of 8,228 eligible procedures, 2,051 patients underwent wedge resections by a thoracic surgeon using the open technique (n = 999) or VATS (n = 1,052). Hospital costs remained significantly higher for open wedge resections than for VATS ($17,377 vs $14,795, P = .000). Surgery time was significantly longer for open resections vs VATS (3.16 vs 2.82 h). Length of stay was 6.34 days for open vs 4.44 days for VATS. Adverse events were significant in the multivariable analysis, with an OR of 1.57 (95% CI, 1.29-1.91) in favor of VATS. CONCLUSIONS: Although this retrospective database analysis could not address the issue of oncologic outcome equivalence, a clear advantage of VATS over open wedge lung cancer resection was found for both acute clinical outcomes and hospital costs.

Video-assisted thoracoscopic lobectomy is less costly and morbid than open lobectomy: a retrospective multiinstitutional database analysis.

BACKGROUND: The Premier Perspective Database (Premier Inc, Charlotte, NC) was used to compare hospital costs and perioperative outcomes for video-assisted thoracoscopic surgery (VATS) and open lobectomy procedures in the United States. METHODS: Eligible patients underwent a lobectomy for cancer by a thoracic surgeon, by VATS or open thoracotomy and were captured in the database between third quarter of 2007 and through 2008. Multivariable logistic regression analyses were performed for binary outcomes. Ordinary least-squares regressions were used to estimate continuous outcomes. All models were adjusted for patient and hospital characteristics. RESULTS: A total of 3,961 patients underwent a lobectomy by a thoracic surgeon by open (n = 2,907) or VATS (n = 1,054) approach. Hospital costs were higher for open versus VATS; $21,016 versus $20,316 (p = 0.027). Adjustment for surgeon experience with VATS over the 6 months prior to each operation showed a significant association between surgeon experience and cost. Average costs ranged from $22,050 for low volume surgeons to $18,133 for high volume surgeons. For open lobectomies, cost differences by surgeon experience were not significant and both levels were estimated at $21,000. Length of stay was 7.83 versus 6.15 days, for open versus VATS (p = 0.000). Surgery duration was shorter for open procedures at 3.75 versus 4.09 for VATS (p = 0.000). The risk of adverse events was significantly lower in the VATS group, odds ratio of 1.22 (p = 0.019). CONCLUSIONS: Lobectomy performed by the VATS approach as compared with an open technique results in shorter length of stay, fewer adverse events, and less cost to the hospital. Economic impact is magnified as the surgeon's experience increases.

Can lung cancer screening by computed tomography be effective in areas with endemic histoplasmosis?

OBJECTIVE: Low-dose chest computed tomography (CT) is being evaluated in several national trials as a screening modality for the early detection of lung cancer. The goal of the present study was to determine whether lung cancer screening could be done while minimizing the number of benign biopsy specimens taken in an area endemic for histoplasmosis. METHODS: The subjects were recruited by letters mailed to area physicians and local advertisement. The inclusion criteria were age older than 50 years and at least a 20 pack-year smoking history. The exclusion criteria were symptoms suggestive of lung cancer or a history of malignancy in the previous 5 years. The participants completed a questionnaire and underwent a chest CT scan at baseline and annually for 5 years. The management of positive screening results was determined using a defined algorithm: annual follow-up CT scan for nodules less than 5 mm; 6-month follow-up CT scan for nodules 5 to 7 mm; review by our multidisciplinary tumor board for nodules 8 to 12 mm; and biopsy for nodules greater than 12 mm. RESULTS: A total of 132 patients were recruited. Of the 132 patients, 61% had positive baseline CT findings and 22% had positive findings on the annual CT scans. Six cancers were detected. Of these 6 patients, 5 had stage I disease and underwent lobectomy, and 1 had stage IIIA disease and underwent induction chemotherapy and radiotherapy followed by lobectomy. All patients were alive and disease free at a mean follow-up of 41.7 ± 18.6 months. No biopsies were performed for benign lesions. Also, no cancers were missed when the protocol was followed. CONCLUSIONS: Screening with CT can be done effectively in an area endemic for histoplasmosis while minimizing benign biopsies.

Sustained CTL activation by murine pulmonary epithelial cells promotes the development of COPD-like disease.

Chronic obstructive pulmonary disease (COPD) is a lethal progressive lung disease culminating in permanent airway obstruction and alveolar enlargement. Previous studies suggest CTL involvement in COPD progression; however, their precise role remains unknown. Here, we investigated whether the CTL activation receptor NK cell group 2D (NKG2D) contributes to the development of COPD. Using primary murine lung epithelium isolated from mice chronically exposed to cigarette smoke and cultured epithelial cells exposed to cigarette smoke extract in vitro, we demonstrated induced expression of the NKG2D ligand retinoic acid early transcript 1 (RAET1) as well as NKG2D-mediated cytotoxicity. Furthermore, a genetic model of inducible RAET1 expression on mouse pulmonary epithelial cells yielded a severe emphysematous phenotype characterized by epithelial apoptosis and increased CTL activation, which was reversed by blocking NKG2D activation. We also assessed whether NKG2D ligand expression corresponded with pulmonary disease in human patients by staining airway and peripheral lung tissues from never smokers, smokers with normal lung function, and current and former smokers with COPD. NKG2D ligand expression was independent of NKG2D receptor expression in COPD patients, demonstrating that ligand expression is the limiting factor in CTL activation. These results demonstrate that aberrant, persistent NKG2D ligand expression in the pulmonary epithelium contributes to the development of COPD pathologies.