Tunneling diodes based on polymer infiltrated vertically aligned carbon nanotube forests.

We report the fabrication and characterization of metal-insulator-metal diodes incorporating vertically aligned carbon nanotube (VACNT) arrays encased in polymer for applications in high frequency optoelectronics. Polydimethylsiloxane (PDMS) and epoxy infiltrating media are used in this study. VACNT forests are embedded with polymer to form a planarized surface over which an array of tunneling diodes is fabricated. Diodes comprising Al2O3 and HfO2 dielectric multilayers achieve highly nonlinear and asymmetric current-voltage characteristics. Results show that asymmetry in excess of 92 can be achieved with multi-insulator barrier tuning, though there is a strong correlation between asymmetry, resistance, and device longevity. With our best performing and most stable device structure (PDMS-VACNT/Al2O3-HfO2-Al2O3-HfO2/PEDOT:PSS), we provide a demonstration of optical-to-d.c. rectification at 638 nm, realizing a current responsivity of 0.65 µA W-1. Our approach to fabricating these VACNT diode arrays is facile and highly scalable. It is capable of being integrated with solution-processed materials and soft lithography techniques to create flexible devices for optical and infrared detection.

Effect of Ventricular Arrhythmia Ablation in Patients With Heart Mate II Left Ventricular Assist Devices: An Evaluation of Ablation Therapy.

BACKGROUND: Patients with advanced heart failure (HF) are predisposed to ventricular arrhythmias (VAs), particularly following implantation of a left ventricular assist device (LVAD). There is minimal evidence for appropriate management strategies. OBJECTIVES: This study aimed to compare the burden of VA and response to ablation performed either before or following LVAD implantation. METHODS: We created a retrospective cohort of patients who underwent both VA ablation and Heart Mate II (Thoratec, Pleasanton, CA, USA) LVAD implantation at Mayo Clinic (Rochester, MN, USA). Patients were stratified based on whether they underwent VA ablation before (pre-LVAD) or after LVAD (post-LVAD) implantation. Descriptive analyses assessed 6-month arrhythmia burden in relation to LVAD implantation and VA ablation. RESULTS: A total of 9 patients underwent both LVAD implantation and VA ablation. There were 3 and 6 patients, respectively, in the pre-LVAD and post-LVAD cohorts. Among patients in the pre-LVAD cohort, the median number of VAs tended to increase after ablation (9 vs. 72) and decreased after LVAD implantation (72 vs. 63). Similarly among patients in the post-LVAD cohort, the median burden of VAs increased after LVAD implantation (1 vs. 22) and the median burden decreased after ablation (22 vs. 13). Two of 6 patients had substrate related to the LVAD inflow cannula site, while other substrate was not related directly to the cannula. CONCLUSIONS: In patients with progressive HF and LVAD implantation, ablation is associated with reduced VA rates. In LVAD patients, most VAs arise from substrate unrelated to the inflow cannula site.

Long-Term Outcomes of Huber Opposition Transfer for Augmenting Hypoplastic Thumb Function.

PURPOSE: This study was conducted to report the functional outcomes of the Huber opposition transfer (abductor digiti minimi muscle) in types II and IIIA hypoplastic thumbs. METHODS: Patients who had undergone a Huber opposition transfer with at least 5 years of follow-up were included in this study. There were 21 thumbs included; 12 returned for a detailed evaluation and 9 were included with a medical record review. Outcome measures included range of motion and pinch strength; Pediatric Outcomes Data Collection Instrument (PODCI) and Patient-Reported Outcomes Measurement Information System (PROMIS) scores were collected on those who could return. There were 15 type II and 6 type IIIA thumbs. RESULTS: Range of motion was significantly less than normal for both the interphalangeal and the metacarpophalangeal joints. For the returning cohort, key and tripod pinch were 44% and 65% of normal. The median Kapandji score was 9 (range, 6-10). The PODCI scores were high for global, upper extremity function, happiness, and pain. The PROMIS scores were similar to normal, except for parent reports of physical function. For all included patients, there was a revision surgery rate of 22%, primarily related to persistent instability. CONCLUSIONS: At a minimum 5-year follow-up, the Huber opposition transfer for types II and IIIA thumbs was shown to provide good subjective outcomes, despite limited range of motion and strength. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Outcomes Following Cubital Tunnel Surgery in Young Patients: The Importance of Nerve Mobility.

PURPOSE: To investigate the outcomes following surgical management of unstable and stable ulnar nerves at the elbow in young patients. METHODS: We retrospectively reviewed the charts of 67 patients who were 30 years old or younger when they underwent primary cubital tunnel surgery at our institution over a 10-year period. In 34 (45%) of these patients, the ulnar nerve either subluxated or perched on the medial epicondyle with elbow flexion and made up the "unstable" cohort. The remaining 42 patients made up the "stable" cohort. Preoperative, intraoperative, and postoperative data were obtained from the patients' charts. Thirty-nine patients completed the following outcome measures: Quick Disabilities of the Arm, Shoulder, and Hand (QuickDASH), visual analog scale (VAS) for pain and treatment satisfaction, return to sport or full activities, and the presence of persistent symptoms. RESULTS: At an average of 5.6 years following surgery, the unstable cohort had a significantly lower QuickDASH score (6.4 vs 18.6) and a significantly higher VAS for treatment satisfaction (8.7 vs 5.9) compared with the stable cohort. The unstable cohort was also significantly less likely to experience residual symptoms (43% vs 94%), persistent numbness (39% vs 44%), or persistent tingling (22% vs 56%) compared with the stable cohort. Within the stable cohort, patients who underwent simultaneous carpal tunnel release exhibited improved VAS and QuickDASH scores compared with patients who did not. There were no differences in time to return to sports or full activities or pain VAS between the two groups. CONCLUSIONS: Surgical management of young patients with symptomatic, unstable ulnar nerves results in superior subjective outcomes compared with surgery in young patients with stable ulnar nerves. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic III.

A novel cardiomyocyte-enriched microRNA, miR-378, targets insulin-like growth factor 1 receptor: implications in postnatal cardiac remodeling and cell survival.

Postnatal cardiac remodeling is characterized by a marked decrease in the insulin-like growth factor 1 (IGF1) and IGF1 receptor (IGF1R) expression. The underlying mechanism remains unexplored. This study examined the role of microRNAs in postnatal cardiac remodeling. By expression profiling, we observed a 10-fold increase in miR-378 expression in 1-week-old neonatal mouse hearts compared with 16-day-old fetal hearts. There was also a 4-6-fold induction in expression of miR-378 in older (10 months) compared with younger (1 month) hearts. Interestingly, tissue distribution analysis identified miR-378 to be highly abundant in heart and skeletal muscles. In the heart, specific expression was observed in cardiac myocytes, which was inducible by a variety of stressors. Overexpression of miR-378 enhanced apoptosis of cardiomyocytes by direct targeting of IGF1R and reduced signaling in Akt cascade. The inhibition of miR-378 by its anti-miR protected cardiomyocytes against H(2)O(2) and hypoxia reoxygenation-induced cell death by promoting IGF1R expression and downstream Akt signaling cascade. Additionally, our data show that miR-378 expression is inhibited by IGF1 in cardiomyocytes. In tissues such as fibroblasts and fetal hearts, where IGF1 levels are high, we found either absent or significantly low miR-378 levels, suggesting an inverse relationship between these two factors. Our study identifies miR-378 as a new cardioabundant microRNA that targets IGF1R. We also demonstrate the existence of a negative feedback loop between miR-378, IGF1R, and IGF1 that is associated with postnatal cardiac remodeling and with the regulation of cardiomyocyte survival during stress.

Time Trends in Perioperative Characteristics and Health Outcomes in Hispanic Patients Undergoing Primary Total Knee Arthroplasty.

OBJECTIVE: This study analyzed the yearly trends in procedure utilization, comorbidity profiles, hospital length of stay (LOS), and 30-day outcomes in Hispanic/Latino patients undergoing primary total knee arthroplasty (TKA). Risk stratification for the development of postsurgical adverse events (AEs) was also investigated. METHODS: The American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) was queried for all Hispanic/Latino patients who underwent primary, elective TKA between 2011 and 2017. Thirty-day outcomes and risk factors were determined using multivariate models that controlled for baseline and perioperative differences. RESULTS: A total of 12,767 Hispanic/Latino patients were identified. Over the study period, the rate of TKA utilization increased by 108%. During the same time, there were significant reductions in the rates of COPD (1.9% vs. 2.9%, p = 0.015), anemia (18.0% vs. 23.5%, p < 0.001), dyspnea (2.9% vs. 4.0%, p = 0.006), and procedure length > 100 min (35.2% vs. 39.4%, p < 0.001). Postoperatively, there was a significant decrease in LOS > 2 days (41.3% vs. 75.6%, p < 0.001), but there was an increase in the rate of developing 30-day AEs (5.8% vs. 4.7%, p = 0.046). Independent risk factors for 30-day AEs included age > 65 years, male sex, chronic steroid use, ASA > 2, diabetes, bleeding disorder, chronic kidney disease, and procedure length > 100 min. CONCLUSION: While the recent trends in procedure utilization, comorbidity profiles, and LOS in Hispanic/Latino patients undergoing primary TKA are reassuring, these have not been accompanied with improved postoperative safety. Patients with bleeding disorders, chronic steroid use, and those admitted from facilities other than home appear to be at highest risk for developing 30-day AEs.

Gender and Total Joint Arthroplasty: Variable Outcomes by Procedure Type.

BACKGROUND: Recent reports on the influence of gender on the outcomes of total joint arthroplasty were limited by either lack of longitudinal data or absent stratification by total hip arthroplasty (THA) or total knee arthroplasty (TKA). As a result, there remains a lack of clarity on this topic. METHODS: The American College of Surgeons National Surgical Quality Improvement Program was queried for all primary, elective THAs and TKAs performed between 2011 and 2017. Differences in demographics, comorbidity profiles, operative time, hospital length of stay (LOS), and 30-day outcomes were compared between male and female patients. Multivariate analyses were performed separately for THA and TKA. RESULTS: A total of 418,885 patients were analyzed; 59.1% were females. Compared with males, females were likely to be older, have a higher body mass index, identify as nonwhite, and require preoperative functional assistance (P < .001). Females had lower rates of diabetes, hypertension, anemia, and kidney disease but a higher rate of chronic steroid use (P < .001). They were also likely to have shorter operative times for both THA and TKA (P < .001). After controlling for the aforementioned differences, female gender was an independent risk factor for readmission, reoperation, and wound infection after THA (P < .001). In contrast, male sex was an independent risk factor for readmission, reoperation, and overall complications after TKA (P < .001). Regardless of the procedure, females were 64%-82% more likely to require an LOS >2 days than males. DISCUSSION: A variable effect of gender was observed on the post-total joint arthroplasty LOS and outcomes depending on the procedure type (THA or TKA). Differences attributed to gender should be accounted for in risk-stratification models. Future studies are also needed to elucidate the underlying causes of gender differences in joint arthroplasty.

Adjuvant Chemotherapy Is Associated With Improved Survival in Locally Invasive Node Negative Non-Small Cell Lung Cancer.

BACKGROUND: The objectives of this study are to explore factors that are associated with use of adjuvant chemotherapy and to evaluate its impact on overall survival in node-negative patients who undergo lung and chest wall resection for non-small cell lung cancer (NSCLC). METHODS: Patients who underwent concomitant lung and chest wall resection for NSCLC were abstracted from the National Cancer Database. Clinical, pathologic, treatment, and follow-up data were obtained. Patients with pathologic nodal metastases or patients who received any radiation treatment were excluded, and the cohort was dichotomized based on administration of adjuvant postoperative chemotherapy. RESULTS: Between 1998 and 2010, 824 patients met the inclusion criteria. This cohort exclusively consisted of pT3 N0 patients who did not receive any induction treatment or adjuvant radiation treatment. Adjuvant chemotherapy was administered to 255 patients (31%). Patients in the chemotherapy group were younger and had shorter inpatient length of stay. Both groups had similar comorbidities, tumor size, unplanned readmission rate, and incomplete resection rate. In multivariable analysis, younger age and shorter length of stay were associated with a greater likelihood of receiving adjuvant chemotherapy. Adjuvant chemotherapy was associated with improved survival (hazard ratio 0.74, 95% CI: 0.6 to 0.9), whereas increasing age, white race, length of inpatient stay, tumor size, and residual tumor were independently associated with greater risk of death. CONCLUSIONS: Patients who undergo lobectomy with chest wall resection for locally advanced NSCLC should be strongly considered for postoperative adjuvant chemotherapy even in the absence of nodal disease. Actual selection of patients for adjuvant chemotherapy is affected by perioperative factors.

Adjuvant Chemotherapy for Patients with T2N0M0 NSCLC.

BACKGROUND: Adjuvant chemotherapy improves survival in patients with completely resected stage II and III NSCLC. However, its role in patients with stage IB NSCLC disease remains unclear. We evaluated the role of adjuvant chemotherapy in a large data set of patients with completely resected T2N0M0 NSCLC. METHODS: Patients with pathologic stage T2N0M0 NSCLC who underwent complete (R0) resection between 2004 and 2011 were identified from the National Cancer Data Base and classified into four groups based on tumor size: 3.1 to 3.9 cm, 4 to 4.9 cm, 5 to 5.9 cm, and 6 to 7 cm. Patients who died within 1 month after their operation were excluded. Survival curves were estimated by the Kaplan-Meier product-limit method and compared by log-rank test. RESULTS: Among the 25,267 patients who met the inclusion criteria, there were 4996 (19.7%) who received adjuvant chemotherapy. Adjuvant chemotherapy was associated with improved median and 5-year overall survival compared with observation for all tumor size groups. In patients with T2 tumors smaller than 4 cm, adjuvant chemotherapy was associated with improved median and 5-year overall survival in univariate (101.6 versus 68.2 months [67% versus 55%], hazard ratio [HR] = 0.66, 95% confidence interval [CI]: 0.61-0.72, p < 0.0001) and multivariable analysis (HR = 0.77, 95% CI: 0.70-0.83, p < 0.001) as well as propensity-matched score (101.6 versus 78.9 months [68% versus 60%], HR = 0.75, 95% CI: 0.70-0.86; p < 0.0001). CONCLUSIONS: In patients with completely resected T2N0M0, adjuvant chemotherapy is associated with improved survival in all tumor size groups. The benefit in patients with tumors smaller than 4 cm strongly suggests a role for chemotherapy in this patient population and counters its current status as an exclusion criteria for adjuvant trials.

Pneumonectomy for Clinical Stage IIIA Non-Small Cell Lung Cancer: The Effect of Neoadjuvant Therapy.

BACKGROUND: The role of pneumonectomy after neoadjuvant therapy for stage IIIA non-small cell lung cancer (NSCLC) remains uncertain. METHODS: Patients who underwent pneumonectomy for clinical stage IIIA NSCLC were abstracted from the National Cancer Database. Individuals treated with neoadjuvant therapy, followed by resection, were compared with those who underwent resection, followed by adjuvant therapy. Logistic regression was performed to identify factors associated with 30-day mortality. A Cox proportional hazards model was fitted to identify factors associated with survival. RESULTS: Pneumonectomy for stage IIIA NSCLC with R0 resection was performed in 1,033 patients; of these, 739 (71%) received neoadjuvant therapy, and 294 (29%) underwent resection, followed by adjuvant therapy. The two groups were well matched for age, gender, race, income, Charlson comorbidity score, and tumor size. The 30-day mortality rate in the neoadjuvant group was 7.8% (57 of 739). Median survival was similar between the two groups: 25.9 months neoadjuvant vs 31.3 months adjuvant (p = 0.74). A multivariable logistic regression model for 30-day mortality demonstrated that increasing age, annual income of less than $35,000, nonacademic facility, and right-sided resection were associated with an elevated risk of 30-day mortality. A multivariable Cox model for survival demonstrated that increasing age was predictive of shorter survival and that administration of neoadjuvant therapy did not confer a survival advantage over adjuvant therapy (p = 0.59). CONCLUSIONS: Most patients who require pneumonectomy for clinical stage IIIA NSCLC receive neoadjuvant chemoradiotherapy, without an improvement in survival. In these patients, primary resection, followed by adjuvant chemoradiotherapy, may provide equivalent long-term outcomes.

Patterns of care in hilar node-positive (N1) non-small cell lung cancer: A missed treatment opportunity?

BACKGROUND: For patients with non-small cell lung cancer (NSCLC) metastatic to hilar lymph nodes (N1), guidelines recommend surgery and adjuvant chemotherapy in operable patients and chemoradiation (CRT) for those deemed inoperable. It is unclear how these recommendations are applied nationally, however. METHODS: The National Cancer Database was queried to identify patients with a tumor <7 cm (T1/T2) with clinically positive N1 nodes. Patients undergoing CRT (comprising chemotherapy and radiation >45 Gy) or surgical resection were considered adequately treated. Remaining patients were classified as receiving inadequate or no treatment. RESULTS: Of the 20,366 patients who met the study criteria, 63% underwent adequate treatment (48% surgical resection, 15% CRT). The remainder received inadequate treatment (23%) or no treatment (14%). In univariate analysis, the patients receiving inadequate or no treatment were older, tended to be non-Caucasian, had a lower income, and had a higher comorbidity score. Patients undergoing adequate treatment had improved overall survival (OS) compared with those receiving inadequate or no treatment (median OS, 34.0 months vs 11.7 months; P < .001). Of those receiving adequate treatment, logistic regression identified several variables associated with surgical resection, including treatment at an academic facility, Caucasian race, and annual income >$35,000. Increasing age and T2 stage were associated with nonoperative management. Following propensity score matching of 2308 patient pairs undergoing surgery or CRT, resection was associated with longer median OS (34.1 months vs 22.0 months; P < .001). CONCLUSIONS: Despite the established guidelines, many patients with T1-2N1 NSCLC do not receive adequate treatment. Surgery is associated with prolonged survival in selected patients. Surgical input in the multidisciplinary evaluation of these patients should be mandatory.

Unexpected readmission after lung cancer surgery: A benign event?

OBJECTIVE: The study objective was to study the incidence, predictors, and implications of unanticipated early postoperative readmission after lung resection for non-small cell lung cancer. METHODS: Patients undergoing surgery for clinical stage I to III non-small cell lung cancer were abstracted from the National Cancer Database. Regression models were fitted to identify predictors of 30-day readmission and to study the association of unplanned readmission with 30-day and long-term survival. RESULTS: Between 1998 and 2010, 129,893 patients underwent resection for stage I to III non-small cell lung cancer. Of these, 5624 (4.3%) were unexpectedly readmitted within 30 days. In a multivariate regression model, increasing age, male gender, preoperative radiation, and pneumonectomy (odds ratio, 1.77; 95% confidence interval, 1.56-2.00) were associated with unexpected readmissions. Longer index hospitalization and higher Charlson comorbidity score were also predictive of readmission. The 30-day mortality for readmitted patients was higher (3.9% vs 2.8%), as was the 90-day mortality (7.0% vs 3.3%, both P < .001). In a multivariate Cox proportional hazards model of long-term survival, increasing age, higher Charlson comorbidity score, and higher pathologic stage (hazard ratio, for stage III 1.81; 95% confidence interval, 1.42-2.29) were associated with greater risk of mortality. Unplanned readmission was independently associated with a higher risk of long-term mortality (hazard ratio, 1.40; 95% confidence interval, 1.34-1.47). The median survival for readmitted patients was significantly shorter (38.7 vs 58.5 months, P < .001). CONCLUSIONS: Unplanned readmissions are not rare after resection for non-small cell lung cancer. Such events are associated with a greater risk of short- and long-term mortality. With the renewed national focus on readmissions and potential financial disincentives, greater resource allocation is needed to identify patients at risk and develop measures to avoid the associated adverse outcomes.

Intraoperative conversion from video-assisted thoracoscopic surgery lobectomy to open thoracotomy: a study of causes and implications.

OBJECTIVE: To study causes and implications of intraoperative conversion to thoracotomy during video-assisted thoracoscopic surgery (VATS) lobectomy. METHODS: We performed an institutional review of patients undergoing lobectomy for known or suspected lung cancer with root cause analysis of every conversion from VATS to open thoracotomy. RESULTS: Between 2004 and 2012, 1227 patients underwent lobectomy. Of these, 517 procedures (42%) were completed via VATS, 87 procedures (7%) were converted to open procedures, and 623 procedures (51%) were performed via planned thoracotomy. Patients undergoing thoracotomy were younger and had a higher incidence of prior lung cancers. Planned thoracotomy and conversion group patients had higher clinical T stage than patients in the VATS group, whereas the planned thoracotomy group had higher pathologic stage than patients in the other groups. Postoperative complications were more frequent in patients in the conversion group (46%) than in the VATS group (23%; P < .001), but similar to the open group (42%; P = .56). Validating a previous classification of causes for conversion, 22 out of 87 conversions (25%) were due to vascular causes, 56 conversions (64%) were for anatomy (eg, adhesions or tumor size), and 8 conversions (9%) were the result of lymph nodes. No specific imaging variables predicted conversion. Within the conversion groups, emergent (20 out of 87; 23%) and planned (67 out of 87; 77%) conversion groups were similar in patient and tumor characteristics and incidence of perioperative morbidity. The conversion rate for VATS lobectomy dropped from 21 out of 74 (28%), to 29 out of 194 (15%), to 37 out of 336 (11%) (P < .001) over 3-year intervals. Over the same periods, the proportion of operations started via VATS increased significantly. CONCLUSIONS: With increasing experience, a higher proportion of lobectomy operations can be completed thoracoscopically. VATS should be strongly considered as the initial approach for the majority of patients undergoing lobectomy.

Effects of Delayed Surgical Resection on Short-Term and Long-Term Outcomes in Clinical Stage I Non-Small Cell Lung Cancer.

BACKGROUND: Conflicting evidence currently exists regarding the causes and effects of delay of care in non-small cell lung cancer (NSCLC). We hypothesized that delayed surgery in early-stage NSCLC is associated with worse short-term and long-term outcomes. METHODS: Treatment data of clinical stage I NSCLC patients undergoing surgical resection were obtained from the National Cancer Data Base (NCDB). Treatment delay was defined as resection 8 weeks or more after diagnosis. Propensity score matching for patient and tumor characteristics was performed to create comparable groups of patients receiving early (less than 8 weeks from diagnosis) and delayed surgery. Multivariable regression models were fitted to evaluate variables influencing delay of surgery. RESULTS: From 1998 to 2010, 39,995 patients with clinical stage I NSCLC received early surgery, while 15,658 patients received delayed surgery. Of these, 27,022 propensity-matched patients were identified. Those with a delay in care were more likely to be pathologically upstaged (18.3% stage 2 or higher versus 16.6%, p < 0.001), have an increased 30-day mortality (2.9% vs 2.4%, p = 0.01), and have decreased median survival (57.7 ± 1.0 months versus 69.2 ± 1.3 months, p < 0.001). Delay in surgery was associated with increasing age, non-white race, treatment at an academic center, urban location, income less than $35,000, and increasing Charlson comorbidity score (p < 0.0001 for all). Delayed patients were more likely to receive a sublobar resection (17.2% vs 13.1%, p < 0.001). CONCLUSIONS: Patients receiving delayed resection for clinical stage I NSCLC have higher comorbidity scores that may affect ability to perform lobectomy and result in higher perioperative mortality. However, delay in resection is independently associated with increased rates of upstaging and decreased median survival. Strategies to minimize delay while medically optimizing higher risk patients are needed.

Pathologic Upstaging in Patients Undergoing Resection for Stage I Non-Small Cell Lung Cancer: Are There Modifiable Predictors?

BACKGROUND: A substantial proportion of patients with clinical stage I non-small cell lung cancer (NSCLC) have more advanced disease on final pathologic review. We studied potentially modifiable factors that may predict pathologic upstaging. METHODS: Data of patients with clinical stage I NSCLC undergoing resection were obtained from the National Cancer Database. Univariate and multivariate analyses were performed to identify variables that predict upstaging. RESULTS: From 1998 to 2010, 55,653 patients with clinical stage I NSCLC underwent resection; of these, 9,530 (17%) had more advanced disease on final pathologic review. Of the 9,530 upstaged patients, 27% had T3 or T4 tumors, 74% had positive lymph nodes (n > 0), and 4% were found to have metastatic disease (M1). Patients with larger tumors (38 mm vs 29 mm, p < 0.001) and a delay greater than 8 weeks from diagnosis to resection were more likely to be upstaged. Upstaged patients also had more lymph nodes examined (10.9 vs 8.2, p < 0.001) and were more likely to have positive resection margins (10% vs 2%, p < 0.001). Median survival was lower in upstaged patients (39 months vs 73 months). Predictors of upstaging in multivariate regression analysis included larger tumor size, delay in resection greater 8 weeks, positive resection margins, and number of lymph nodes examined. There was a linear relationship between the number of lymph nodes examined and the odds of upstaging (1 to 3 nodes, odds ratio [OR] 2.01; >18 nodes OR 6.14). CONCLUSIONS: Pathologic upstaging is a common finding with implications for treatment and outcomes in clinical stage I NSCLC. A thorough analysis of regional lymph nodes is critical to identify patients with more advanced disease.

The Role of Surgical Resection in Stage IIIA Non-Small Cell Lung Cancer: A Decision and Cost-Effectiveness Analysis.

BACKGROUND: This study evaluated the cost-effectiveness of combination chemotherapy, radiotherapy, and surgical intervention (CRS) vs definitive chemotherapy and radiotherapy (CR) in clinical stage IIIA non-small cell lung cancer (NSCLC) patients at academic and nonacademic centers. METHODS: Patients with clinical stage IIIA NSCLC receiving CR or CRS from 1998 to 2010 were identified in the National Cancer Data Base. Propensity score matching on patient, tumor, and treatment characteristics was performed. Medicare allowable charges were used for treatment costs. The incremental cost-effectiveness ratio (ICER) was based on probabilistic 5-year survival and calculated as cost per life-year gained. RESULTS: We identified 5,265 CR and CRS matched patient pairs. Surgical resection imparted an increased effectiveness of 0.83 life-years, with an ICER of $17,618. Among nonacademic centers, 1,634 matched CR and CRS patients demonstrated a benefit with surgical resection of 0.86 life-years gained, for an ICER of $17,124. At academic centers, 3,201 matched CR and CRS patients had increased survival of 0.81 life-years with surgical resection, for an ICER of $18,144. Finally, 3,713 CRS patients were matched between academic and nonacademic centers. Academic center surgical patients had an increased effectiveness of 1.5 months gained and dominated the model with lower surgical cost estimates associated with lower 30-day mortality rates. CONCLUSIONS: In stage IIIA NSCLC, the selective addition of surgical resection to CR is cost-effective compared with definitive chemoradiation therapy at nonacademic and academic centers. These conclusions are valid over a range of clinically meaningful variations in cost and treatment outcomes.

Treatment Outcomes in Stage I Lung Cancer: A Comparison of Surgery and Stereotactic Body Radiation Therapy.

INTRODUCTION: The relative roles of surgery and stereotactic body radiation therapy in stage I non-small-cell lung cancer (NSCLC) are evolving particularly for marginally operable patients. Because there is limited prospective comparative data for these treatment modalities, we evaluated their relative use and outcomes at the population level using a national database. METHODS: Patient variables and treatment-related outcomes were abstracted for patients with clinical stage I NSCLC from the National Cancer Database. Patients receiving surgery were compared with those undergoing stereotactic body radiation therapy (SBRT) in exploratory unmatched and subsequent propensity matched analyses. RESULTS: Between 1998 and 2010, 117,618 patients underwent surgery or SBRT for clinical stage I NSCLC. Of these, 111,731 (95%) received surgery, whereas 5887 (5%) underwent SBRT. Patients in the surgery group were younger, more likely to be males, and had higher Charlson comorbidity scores. SBRT patients were more likely to have T1 (versus T2) tumors and receive treatment at academic centers. Thirty-day surgical mortality was 2596 of 109,485 (2.4%). Median overall survival favored the surgery group in both unmatched (68.4 versus 33.3 months, p < 0.001) and matched analysis based on patient characteristics (62.3 versus 33.1 months, p < 0.001). Disease-specific survival was unavailable from the data set. CONCLUSION: In a propensity matched comparison, patients selected for surgery have improved survival compared with SBRT. In the absence of information on cause of death and with limited variables to characterize comorbidity, it is not possible to assess the relative contribution of patient selection or better cancer control toward the improved survival. Rigorous prospective studies are needed to optimize patient selection for SBRT in the high-risk surgical population.

Multidisciplinary Treatment for Stage IIIA Non-Small Cell Lung Cancer: Does Institution Type Matter?

BACKGROUND: Improved survival of patients with early-stage non-small cell lung cancer (NSCLC) undergoing resection at high-volume centers has been reported. However, the effect of institution is unclear in stage IIIA NSCLC, where a variety of neoadjuvant and adjuvant therapies are used. METHODS: Treatment and outcomes data of clinical stage IIIA NSCLC patients undergoing resection as part of multimodality therapy was obtained from the National Cancer Database. Multivariable regression models were fitted to evaluate variables influencing 30-day mortality and overall survival. RESULTS: From 1998 to 2010, 11,492 clinical stage IIIA patients underwent resection at community centers, and 7,743 patients received resection at academic centers. Academic center patients were more likely to be younger, female, non-Caucasian, have a lower Charlson-Deyo comorbidity score, and to receive neoadjuvant chemotherapy (49.6% vs 40.6%; all p < 0.001). Higher 30-day mortality was associated with increasing age, male gender, preoperative radiotherapy, and pneumonectomy. Patients undergoing operations at academic centers experienced lower 30-day mortality (3.3% vs 4.5%; odds ratio, 0.75; 95% confidence interval [CI], 0.60 to 0.93; p < 0.001). Decreased long-term survival was associated with increasing age, male gender, higher Charlson-Deyo comorbidity score, and larger tumors. Neoadjuvant chemotherapy (hazard ratio, 0.66; 95% CI, 0.62 to 0.70), surgical intervention at an academic center (hazard ratio, 0.92; 95% CI, 0.88 to 0.97), and lobectomy (hazard ratio, 0.72; 95% CI, 0.67 to 0.77) were associated with improved overall survival. CONCLUSIONS: Stage IIIA NSCLC patients undergoing resection at academic centers had lower 30-day mortality and increased overall survival compared with patients treated at community centers, possibly due to higher patient volume and an increased rate of neoadjuvant chemotherapy.

Role for Surgical Resection in the Multidisciplinary Treatment of Stage IIIB Non-Small Cell Lung Cancer.

BACKGROUND: The role of multimodality therapy in stage IIIB non-small cell lung cancer (NSCLC) remains inadequately studied. Although chemoradiation is currently the mainstay of treatment, randomized trials evaluating surgical intervention are lacking, and resection is offered selectively. METHODS: Data from patients with clinical stage IIIB NSCLC (T4N2 or any N3) undergoing definitive multimodality therapy were obtained from the National Cancer Database (NCDB). Multivariable Cox regression models were fitted to evaluate variables influencing overall survival (OS). RESULTS: From 1998 to 2010, 7,459 patients with clinical stage IIIB NSCLC were treated with definitive chemoradiation (CR group), whereas 1,714 patients underwent chemotherapy, radiation, and surgical intervention in any sequence (CRS group). CRS patients were more likely to be younger and white and have slightly smaller tumors (all p < 0.01). There was no difference in Charlson Comorbidity Index (CCI) between the groups (p = 0.5). In the CRS group, 79% of patients received neoadjuvant therapy. Thirty-day surgical mortality was 3%. Factors associated with improved OS in multivariate analysis included younger age, female sex, decreased CCI, smaller tumor size, and surgical resection (hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.52-0.63). Among patients treated with surgical intervention, incomplete resection was associated with decreased OS (HR, 1.52; 95% CI, 1.20-1.92). Median OS was longer in the CRS group (25.9 months versus 16.3 months; p < 0.001). Propensity matched analysis on 631 patient pairs treated with CRS versus CR confirmed these findings (median OS, 28.9 versus 17.2 months; p < 0.001). CONCLUSIONS: Surgical resection as a part of multimodality therapy may be associated with improved OS in highly selected patients with stage IIIB NSCLC. Multidisciplinary evaluation of these patients is critical.

Postoperative radiotherapy for pathologic N2 non-small-cell lung cancer treated with adjuvant chemotherapy: a review of the National Cancer Data Base.

PURPOSE: To investigate the impact of modern postoperative radiotherapy (PORT) on overall survival (OS) for patients with N2 non-small-cell lung cancer (NSCLC) treated nationally with surgery and adjuvant chemotherapy. PATIENTS AND METHODS: Patients with pathologic N2 NSCLC who underwent complete resection and adjuvant chemotherapy from 2006 to 2010 were identified from the National Cancer Data Base and stratified by use of PORT (≥ 45 Gy). A total of 4,483 patients were identified (PORT, n = 1,850; no PORT, n = 2,633). The impact of patient and treatment variables on OS was explored using Cox regression. RESULTS: Median follow-up time was 22 months. On univariable analysis, improved OS correlated with younger age, treatment at an academic facility, female sex, urban population, higher income, lower Charlson comorbidity score, smaller tumor size, multiagent chemotherapy, resection with at least a lobectomy, and PORT. On multivariable analysis, improved OS remained independently predicted by younger age, female sex, urban population, lower Charlson score, smaller tumor size, multiagent chemotherapy, resection with at least a lobectomy, and PORT (hazard ratio, 0.886; 95% CI, 0.798 to 0.988). Use of PORT was associated with an increase in median and 5-year OS compared with no PORT (median OS, 45.2 v 40.7 months, respectively; 5-year OS, 39.3% [95% CI, 35.4% to 43.5%] v 34.8% [95% CI, 31.6% to 38.3%], respectively; P = .014). CONCLUSION: For patients with N2 NSCLC after complete resection and adjuvant chemotherapy, modern PORT seems to confer an additional OS advantage beyond that achieved with adjuvant chemotherapy alone.