Computed Tomography Screening for Lung Cancer: Mediastinal Lymph Node Resection in Stage IA Nonsmall Cell Lung Cancer Manifesting as Subsolid and Solid Nodules.

OBJECTIVE: To compare long-term survival rates of patients with first, primary, clinical stage IA nonsmall cell lung cancer from a large cohort undergoing computed tomography screening with and without mediastinal lymph node resection (MLNR) under an Institutional Review Board-approved common protocol from 1992 to 2014. BACKGROUND: Assessing survival differences of patients with and without MLNR manifesting as solid and subsolid nodules. METHODS: Long-term Kaplan-Meier (K-M) survival rates for those with and without MLNR were compared and Cox regression analyses were used to adjust for demographic, computed tomography, and surgical covariates. RESULTS: The long-term K-M rates for 462 with and 145 without MLNR was 92% versus 96% (P = 0.19), respectively. For 203 patients with a subsolid nodule, 151 with and 52 without MLNR, the rate was 100%. For the 404 patients with a solid nodule, 311 with and 93 without MLNR, the rate was 87% versus 94% (P = 0.24) and Cox regression showed no statistically significant difference (P = 0.28) when adjusted for all covariates. Risk of dying increased significantly with increasing decades of age (hazard ratio [HR] 2.3, 95% confidence interval [CI] 1.4-3.8), centrally located tumor (HR 2.5, 95% CI 1.2-5.2), tumor size 21 to 30 mm (HR 2.7, 95% CI 1.2-6.0), and invasion beyond the lung stroma (HR 3.0, 95% CI 1.4-6.1). For the 346 patients with MLNR, tumor size was 20 mm or less; K-M rates for the 269 patients with and 169 patients without MLNR were also not significantly different (HR 2.1, P = 0.24). CONCLUSIONS: It is not mandatory to perform MLNR when screen-diagnosed nonsmall cell lung cancer manifests as a subsolid nodule.

Statistical learning methods as a preprocessing step for survival analysis: evaluation of concept using lung cancer data.

BACKGROUND: Statistical learning (SL) techniques can address non-linear relationships and small datasets but do not provide an output that has an epidemiologic interpretation. METHODS: A small set of clinical variables (CVs) for stage-1 non-small cell lung cancer patients was used to evaluate an approach for using SL methods as a preprocessing step for survival analysis. A stochastic method of training a probabilistic neural network (PNN) was used with differential evolution (DE) optimization. Survival scores were derived stochastically by combining CVs with the PNN. Patients (n = 151) were dichotomized into favorable (n = 92) and unfavorable (n = 59) survival outcome groups. These PNN derived scores were used with logistic regression (LR) modeling to predict favorable survival outcome and were integrated into the survival analysis (i.e. Kaplan-Meier analysis and Cox regression). The hybrid modeling was compared with the respective modeling using raw CVs. The area under the receiver operating characteristic curve (Az) was used to compare model predictive capability. Odds ratios (ORs) and hazard ratios (HRs) were used to compare disease associations with 95% confidence intervals (CIs). RESULTS: The LR model with the best predictive capability gave Az = 0.703. While controlling for gender and tumor grade, the OR = 0.63 (CI: 0.43, 0.91) per standard deviation (SD) increase in age indicates increasing age confers unfavorable outcome. The hybrid LR model gave Az = 0.778 by combining age and tumor grade with the PNN and controlling for gender. The PNN score and age translate inversely with respect to risk. The OR = 0.27 (CI: 0.14, 0.53) per SD increase in PNN score indicates those patients with decreased score confer unfavorable outcome. The tumor grade adjusted hazard for patients above the median age compared with those below the median was HR = 1.78 (CI: 1.06, 3.02), whereas the hazard for those patients below the median PNN score compared to those above the median was HR = 4.0 (CI: 2.13, 7.14). CONCLUSION: We have provided preliminary evidence showing that the SL preprocessing may provide benefits in comparison with accepted approaches. The work will require further evaluation with varying datasets to confirm these findings.

WITHDRAWN: Dehydrated Human Amnion/Chorion Membrane (Placenta) Reduces Anastomotic Leaks after Esophagectomy.

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Evaluation of Esophageal Anastomotic Integrity With Serial Pleural Amylase Levels.

BACKGROUND: An anastomotic leak is the most devastating and potentially fatal complication after esophagectomy. Current detection methods can be inaccurate and place patients at risk of other complications. Analysis of pleural fluid for amylase may be more accurate and place patients at less of a risk for evaluating the integrity of an esophageal anastomosis. METHODS: We retrospectively reviewed prospective data of 45 consecutive patients who underwent an Ivor Lewis esophagectomy over an 18-month period and evaluated their anastomotic integrity with serial pleural amylase levels (PAL). RESULTS: There were 40 men (89%), and median age was 63 years (range, 35 to 79). Indication for esophagectomy was cancer in 38 patients (84%); 27 (71%) underwent neoadjuvant chemoradiation. A barium swallow was performed in the first 25 patients at median postoperative day (POD) 5 (range, 5 to 10); the swallow was negative in 23 patients (93%). Serial PALs were obtained starting on POD 3 and stopped 1 day after toleration of clear liquids. The PALs in the no-leak patients were highest on POD 3 (median 42 IU/L; range, 20 to 102 IU/L) and decreased (median 15 IU/L; range, 8 to 34 IU/L) to the lowest levels 1 day after clear liquid toleration (p = 0.04). Two patients had a leak and had peak PALs of 227 IU/L and 630 IU/L, respectively; both leaks occurred on POD 4, 1 day before their scheduled swallow test. The last 20 patients underwent serial PALs only, without a planned swallow test or computed tomography scan for anastomotic integrity evaluation. One of these patients had a leak on POD 5 with a low PAL of 55 IU/L the day before the spike of more than 4,000 IU/L. Two of the leaks were treated with esophageal stent placement and intravenous antibiotics, and the remaining patient's leak resolved with intravenous antibiotics, no oral intake, and observation only. None of the leak patients required transthoracic esophageal repair or drainage of an empyema. There was 1 postoperative death (2%) secondary to aspiration pneumonia on POD 10; no leak was ever identified, and the patient had been eating for 3 days before death. Complications occurred in 15 patients (33%), most commonly respiratory; no respiratory issues occurred in PAL-only evaluated patients. No late anastomotic leaks occurred in any patient while in the hospital or after discharge. CONCLUSIONS: Serial PALs for the detection of esophageal anastomotic leaks proved to be accurate, safe, and inexpensive. Elimination of barium swallows and computed tomography scans for evaluation of anastomotic integrity may decrease aspiration risks as well as associated pulmonary failure during the postoperative period. Serial PALs may be the preferred method of detecting an anastomotic leak after esophagectomy. A prospective randomized study is warranted.

Opening wedge high tibial osteotomy: an operative technique and rehabilitation program to decrease complications and promote early union and function.

BACKGROUND: High tibial osteotomy has been associated with significant complications, including delayed union or nonunion, loss of correction, arthrofibrosis, and patella infera. HYPOTHESES: A technique for opening wedge osteotomy that incorporates an autogenous iliac crest bone graft will prevent delayed union or nonunion, allow early rehabilitation and weightbearing, and prevent knee arthrofibrosis and patella infera. Secondly, the authors' methods for calculating the desired correction of valgus alignment prevent undesired alterations in tibial slope. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: A total of 55 consecutive patients who underwent high tibial osteotomy were observed at a mean of 20 months postoperatively. Preoperative and postoperative measurements of radiographs were conducted by independent examiners for bony union, tibial slope, and patellar height. The osteotomy opening size ranged from 5 to 17.5 mm; 35 knees (64%) had openings < or =10 mm, and 20 knees (36%) had openings >11 mm. RESULTS: The osteotomy united in all patients. Three patients had a delay in union, which resolved by 6 to 8 months postoperatively. A loss of fixation occurred in 1 patient, who admitted to full weightbearing immediately after surgery; the osteotomy required revision. The iliac crest graft site healed without complications, and there were no infections, loss of knee motion, nerve or arterial injuries, alterations in tibial slope, or cases of patellar infera postoperatively. Full weightbearing was achieved at a mean of 8 weeks (range, 4-11 weeks) postoperatively. CONCLUSIONS: The operative technique including use of an autologous iliac crest bone graft in addition to a progressive rehabilitation program successfully prevented nonunion, change in tibial slope, and knee arthrofibrosis in this study.

Digital Drainage System Reduces Hospitalization After Video-Assisted Thoracoscopic Surgery Lung Resection.

BACKGROUND: The purpose of this study was to assess the efficacy of a digital versus traditional drainage system on hospitalization for patients undergoing video-assisted thoracoscopic surgery (VATS) anatomic lung resection. METHODS: Consecutive patients who underwent VATS anatomic lung resection (July 2014 through January 2015) for lung cancer were analyzed. Patients were managed with overnight suction (-20 cm H2O) followed by gravity drainage (water seal or -8 cm H2O) in both the traditional and digital drainage systems, respectively; the digital system also allowed for continuous monitoring of air leaks. Chest tubes were removed when the air leak was absent for 12 hours and pleural drainage was less than 300 mL/24 h; patient outcomes selected by propensity matching were compared. RESULTS: The VATS lung resections (lobectomy or segmentectomy) were performed in 108 patients during the 7-month study period. The pleural cavity was drained with the traditional system in 75 patients and with the digital system in 33 patients. By propensity score matching at a 2:1 ratio, 40 patients were placed in the traditional group and 20 patients, in the digital group for analysis. Demographics, percent predicted forced expiratory volume in 1 second, tumor size, stage, and type of resection were similar between the groups. The majority of patients (85%) underwent a lobectomy. There were no operative deaths. Overall complications were fewer in the digital system group (22%) compared with the traditional system group (35%; p = 0.01). Median air leak days (-1.1), chest tube days (-1.6), and total hospital stay (-1.5) were significantly reduced in the digital drainage system group. CONCLUSIONS: Patients undergoing VATS lung resections who were managed postoperatively with a digital drainage system experienced less morbidity and decreased hospitalization. A digital drainage system appears to be a safe alternative for management of the pleural cavity after VATS anatomic lung resection.

Community-Based Multidisciplinary Computed Tomography Screening Program Improves Lung Cancer Survival.

BACKGROUND: Lung cancer is the most common cause of cancer deaths in the United States. Overall survival is less than 20%, with the majority of patients presenting with advanced disease. The National Lung Screening Trial, performed mainly in academic medical centers, showed that cancer mortality can be reduced with computed tomography (CT) screening compared with chest radiography in high-risk patients. To determine whether this survival advantage can be duplicated in a community-based multidisciplinary thoracic oncology program, we initiated a CT scan screening program for lung cancer within an established health care system. METHODS: In 2008, we launched a lung cancer CT screening program within the WellStar Health System (WHS) consisting of five hospitals, three health parks, 140 outpatient medical offices, and 12 imaging centers that provide care in a five-county area of approximately 1.4 million people in Metro-Atlanta. Screening criteria incorporated were the International Early Lung Cancer Action Program (2008 to 2010) and National Comprehensive Cancer Network guidelines (2011 to 2013) for moderate- and high-risk patients. RESULTS: A total of 1,267 persons underwent CT lung cancer screening in WHS from 2008 through 2013; 53% were men, 87% were 50 years of age or older, and 83% were current or former smokers. Noncalcified indeterminate pulmonary nodules were found in 518 patients (41%). Thirty-six patients (2.8%) underwent a diagnostic procedure for positive findings on their CT scan; 30 proved to have cancer, 28 (2.2%) primary lung cancer and 2 metastatic cancer, and 6 had benign disease. Fourteen patients (50%) had their lung cancer discovered on their initial CT scan, 11 on subsequent scans associated with indeterminate pulmonary nodules growth and 3 patients who had a new indeterminate pulmonary nodules. Only 15 (54%) of these 28 patients would have qualified as a National Lung Screening Trial high-risk patient; 75% had stage I or II disease. Overall 5-year survival was 64% and 5-year cancer specific survival was 71% in the screened patients, whereas nonscreened lung cancer patients during that time in WHS had an overall survival of only 19% (p < 0.001). CONCLUSIONS: A community-based multidisciplinary lung cancer screening program can improve survival of patients with lung cancer outside of a large multicenter study. This survival advantage was caused by a significant stage shift to earlier disease. Lung cancer CT screening may also benefit patients not meeting the National Lung Screening Trial criteria who are at moderate or high risk for lung cancer.

Sublobar resection is equivalent to lobectomy for clinical stage 1A lung cancer in solid nodules.

OBJECTIVES: A single randomized trial established lobectomy as the standard of care for the surgical treatment of early-stage non-small cell lung cancer. Recent advances in imaging/staging modalities and detection of smaller tumors have once again rekindled interest in sublobar resection for early-stage disease. The objective of this study was to compare lung cancer survival in patients with non-small cell lung cancer with a diameter of 30 mm or less with clinical stage 1 disease who underwent lobectomy or sublobar resection. METHODS: We identified 347 patients diagnosed with lung cancer who underwent lobectomy (n = 294) or sublobar resection (n = 53) for non-small cell lung cancer manifesting as a solid nodule in the International Early Lung Cancer Action Program from 1993 to 2011. Differences in the distribution of the presurgical covariates between sublobar resection and lobectomy were assessed using unadjusted P values determined by logistic regression analysis. Propensity scoring was performed using the same covariates. Differences in the distribution of the same covariates between sublobar resection and lobectomy were assessed using adjusted P values determined by logistic regression analysis with adjustment for the propensity scores. Lung cancer-specific survival was determined by the Kaplan-Meier method. Cox survival regression analysis was used to compare sublobar resection with lobectomy, adjusted for the propensity scores, surgical, and pathology findings, when adjusted and stratified by propensity quintiles. RESULTS: Among 347 patients, 10-year Kaplan-Meier for 53 patients treated by sublobar resection compared with 294 patients treated by lobectomy was 85% (95% confidence interval, 80-91) versus 86% (confidence interval, 75-96) (P = .86). Cox survival analysis showed no significant difference between sublobar resection and lobectomy when adjusted for propensity scores or when using propensity quintiles (P = .62 and P = .79, respectively). For those with cancers 20 mm or less in diameter, the 10-year rates were 88% (95% confidence interval, 82-93) versus 84% (95% confidence interval, 73-96) (P = .45), and Cox survival analysis showed no significant difference between sublobar resection and lobectomy using either approach (P = .42 and P = .52, respectively). CONCLUSIONS: Sublobar resection and lobectomy have equivalent survival for patients with clinical stage IA non-small cell lung cancer in the context of computed tomography screening for lung cancer.

Balancing curability and unnecessary surgery in the context of computed tomography screening for lung cancer.

OBJECTIVE: Surgical management is a critical component of computed tomography (CT) screening for lung cancer. We report the results for US sites in a large ongoing screening program, the International Early Lung Cancer Action Program (I-ELCAP). METHODS: We identified all patients who underwent surgical resection. We compared the results before (1993-2005) and after (2006-2011) termination of the National Lung Screening Trial to identify emerging trends. RESULTS: Among 31,646 baseline and 37,861 annual repeat CT screenings, 492 patients underwent surgical resection; 437 (89%) were diagnosed with lung cancer; 396 (91%) had clinical stage I disease. In the 54 (11%) patients with nonmalignant disease, resection was sublobar in 48 and lobectomy in 6. The estimated cure rate based on the 15-year Kaplan-Meier survival for all 428 patients (excluding 9 typical carcinoids) with lung cancer was 84% (95% confidence interval [CI], 80%-88%) and 88% (95% CI, 83%-92%) for clinical stage I disease resected within 1 month of diagnosis. Video-assisted thoracoscopic surgery and sublobar resection increased significantly, from 10% to 34% (P < .0001) and 22% to 34% (P = .01) respectively; there were no significant differences in the percentage of malignant diagnoses (90% vs 87%, P = .36), clinical stage I (92% vs 89%, P = .33), pathologic stage I (85% vs 82%, P = .44), tumor size (P = .61), or cell type (P = .81). CONCLUSIONS: The frequency and extent of surgery for nonmalignant disease can be minimized in a CT screening program and provide a high cure rate for those diagnosed with lung cancer and undergoing surgical resection.

Survival analysis of patients with stage I non-small-cell lung cancer using clinical and DNA repair pathway expression variables.

BACKGROUND: Lung cancer is the leading cause of cancer-related mortality. Understanding patient attributes that enhance survival and predict recurrence is necessary to individualize treatment options. METHODS: Patients (N = 162) were dichotomized into favorable (n = 101) and unfavorable (n = 61) groups based on survival characteristics. Ku86 and poly(ADP-ribose) polymerase (PARP) expression measures were incorporated into the analyses. LR, Kaplan-Meier analysis, and Cox regression were used to investigate intervariable relationships and survival. Odds ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (CIs) were used to assess associations. RESULTS: Sex (OR, 0.32; CI-0.14, 0.76), squamous cell carcinoma (SCC) (OR, 0.41; CI-0.17, 0.98), and recurrence (OR, 0.04; CI-0.01, 0.20) confer an unfavorable outcome with area under the receiver operating characteristic curve (Az) = 0.788. Patients with increased tumor grade (OR = 1.84; CI-1.06, 3.19) or increased Ku86 intensity (OR, 2.03; CI-1.08, 3.82) were more likely to be male individuals, and older patients (OR, 1.70; CI-(1.14, 2.52) were more likely to have SCC. Patients older than the median age (HR, 1.86; CI-1.11, 3.12), patients with SCC (HR, 1.78; CI-1.05, 3.01), patients with recurrence (HR, 4.16; CI-2.37, 7.31), and male patients (HR, 2.03; CI-1.20, 3.43) have a higher hazard. None of the DNA repair measures were associated with significant HRs. CONCLUSION: Clinical and pathologic factors that enhance and limit survival for patients with stage I NSCLC were quantified. The DNA repair measures showed little association. These findings are important given that certain clinical and pathologic features are related to better long-term survival outcome than others.

Anvil extension technology in thoracic surgery.

PURPOSE: Endoscopic staplers are the dominant tools to divide tubular structures in thoracoscopic lobectomy. However, passing these devices can be challenging because of limitations in their design. DESCRIPTION: Two independent concepts were combined into one design aiming to overcome the limitation of passing the straight anvil of an endoscopic stapler through a tunnel typically created by a curved dissection instrument within the complex cluster of tubular structures that comprise the pulmonary hilum. EVALUATION: A library of 45 unedited advanced thoracoscopic lung resection videos containing a balance of all major anatomic resections (36 lobectomy and 9 pneumonectomy) spanning 2004 to 2011 were reviewed, and 220 hilar structure division times were measured along with the adjunctive techniques like catheter leaders or silicone slings. Prolonged passage times occurred throughout the series despite improved experience; however, early experience with 51 passes using the new design showed significant time savings (median 61 s versus 115 s, p = 0.005). CONCLUSIONS: Curved tip anvils for endoscopic linear cutting staplers appear useful to speed thoracoscopic lung resections.