Babatunde A. Yerokun

A national analysis of wedge resection versus stereotactic body radiation therapy for stage IA non–small cell lung cancer

Objective Lobectomy is considered optimal therapy for early‐stage non–small cell lung cancer, but sublobar wedge resection and stereotactic body radiation therapy are alternative treatments. This study compared outcomes between wedge resection and stereotactic body radiotherapy. Methods Overall survival of patients with cT1N0 and tumors ≤2 cm who underwent stereotactic body radiotherapy or wedge resection in the National Cancer Data Base from 2008 to 2011 was assessed via a Kaplan‐Meier and propensity score–matched analysis. A center‐level sensitivity analysis that used observed/expected mortality ratios was conducted to identify an association between center use of stereotactic body radiotherapy and mortality. Results Of the 6295 patients included, 1778 (28.2%) underwent stereotactic body radiotherapy, and 4517 (71.8%) underwent wedge resection. Stereotactic body radiotherapy was associated with significantly reduced 5‐year survival compared with wedge resection in both unmatched analysis (30.9% vs 55.2%, P < .001) and after adjustment for covariates (31.0% vs 49.9%, P < .001). Stereotactic body radiotherapy also was associated with worse overall survival than wedge resection after 2 subgroup analyses of propensity‐matched patients (P < .05 for both). Centers that used stereotactic body radiotherapy more often as opposed to surgery for patients with cT1N0 patients with tumors <2 cm were more likely to have an observed/expected mortality ratio > 1 for 3‐year mortality (P = .034). Conclusions In this national analysis, wedge resection was associated with better survival for stage IA non–small cell lung cancer than stereotactic body radiotherapy.

Induction chemoradiation therapy prior to esophagectomy is associated with superior long-term survival for esophageal cancer

The purpose of this study was to examine the role of induction chemoradiation in the treatment of potentially resectable locally advanced (T2-3N0 and T1-3N+) esophageal cancer utilizing a large national database. The National Cancer Data Base (NCDB) was queried for all patients undergoing esophagectomy for clinical T2-3N0 and T1-3N+ esophageal cancer of the mid- or lower esophagus. Patients were stratified by the use of induction chemoradiation therapy versus surgery-first. Trends were assessed with the Cochran-Armitage test. Predictors of receiving induction therapy were evaluated with multivariable logistic regression. A propensity-matched analysis was conducted to compare outcomes between groups, and the Kaplan-Meier method was used to estimate long-term survival. Within the NCDB, 7921 patients were identified, of which 6103 (77.0%) were treated with chemoradiation prior to esophagectomy, while the remaining 1818 (23.0%) were managed with surgery-first. Use of induction therapy increased over time, with an absolute increase of 11.8% from 2003-2011 (P < 0.001). As revealed by the propensity model, induction therapy was associated with higher rates of negative margins and shorter hospital length of stay, but no differences in unplanned readmission and 30-day mortality rates. In unadjusted survival analysis, induction therapy was associated with better long-term survival compared to a strategy of surgery-first, with 5-year survival rates of 37.2% versus 28.6%, P < 0.001. Following propensity score matching analysis, the use of induction therapy maintained a significant survival advantage over surgery-first (5-year survival: 37.9% vs. 28.7%, P < 0.001). Treatment with induction chemoradiation therapy prior to surgical resection is associated with significant improvement in long-term survival, even after adjusting for confounders with a propensity model. Induction therapy should be considered in all medically appropriate patients with resectable cT2-3N0 and cT1-3N+ esophageal cancer, prior to esophagectomy.

Effect of Obesity and Underweight Status on Perioperative Outcomes of Congenital Heart Operations in Children, Adolescents, and Young Adults: An Analysis of Data from the Society of Thoracic Surgeons Database.

Background: Extreme body mass index (BMI; either very high or very low) has been associated with increased risk of adverse perioperative outcome in adults undergoing cardiac surgery. The effect of BMI on perioperative outcomes in congenital heart disease patients has not been evaluated. Methods: A multicenter retrospective cohort study was performed studying patients 10 to 35 years of age undergoing a congenital heart disease operation in the Society of Thoracic Surgeons Congenital Heart Surgery Database between January 1, 2010, and December 31, 2015. The primary outcomes were operative mortality and a composite outcome (1 or more of operative mortality, major adverse event, prolonged hospital length of stay, and wound infection/dehiscence). The associations between age- and sex-adjusted BMI percentiles and these outcomes were assessed, with adjustment for patient-level risk factors, with multivariate logistic regression. Results: Of 18 337 patients (118 centers), 16% were obese, 15% were overweight, 53% were normal weight, 7% were underweight, and 9% were severely underweight. Observed risks of operative mortality (P=0.04) and composite outcome (P<0.0001) were higher in severely underweight and obese subjects. Severely underweight BMI was associated with increased unplanned cardiac operation and reoperation for bleeding. Obesity was associated with increased risk of wound infection. In multivariable analysis, the association between BMI and operative mortality was no longer significant. Obese (odds ratio, 1.28; P=0.008), severely underweight (odds ratio, 1.29; P<0.0001), and underweight (odds ratio, 1.39; P=0.002) subjects were associated with increased risk of composite outcome. Conclusions: Obesity and underweight BMI were associated with increased risk of composite adverse outcome independently of other risk factors. Further research is necessary to determine whether BMI represents a modifiable risk factor for perioperative outcome.

Clinical predictors and outcome implications of early readmission in lung transplant recipients

BACKGROUND The purpose of this study was to identify risk factors and outcome implications for 30-day hospital readmission in lung transplant recipients. METHODS We conducted a retrospective cohort study of lung transplant cases from a single, high-volume lung transplant program between January 2000 and March 2012. Demographic and health data were reviewed for all patients. Risk factors for 30-day readmission (defined as readmission within 30 days of discharge from index lung transplant hospitalization) were modeled using logistic regression, with selection of parameters by backward elimination. RESULTS The sample comprised 795 patients after excluding scheduled readmissions and in-hospital deaths. Overall 30-day readmission rate was 45.4% (n = 361). Readmission rates were similar across different diagnosis categories and procedure types. By univariate analysis, post-operative complications that predisposed to 30-day readmission included pneumonia, any infection, and atrial fibrillation (all p < 0.05). In the final multivariate model, occurrence of any post-transplant complication was the most significant risk factor for 30-day readmission (odds ratio = 1.764; 95% confidence interval, 1.259-2.470). Even for patients with no documented perioperative complication, readmission rates were still >35%. Kaplan-Meier analysis and multi-variate regression modeling to assess readmission as a predictor of long-term outcomes showed that 30-day readmission was not a significant predictor of worse survival in lung recipients. CONCLUSIONS Occurrence of at least 1 post-transplant complication increases risk for 30-day readmission in lung transplant recipients. In this patient population, 30-day readmission does not predispose to adverse long-term survival. Quality indicators other than 30-day readmission may be needed to assess hospitals that perform lung transplantation.

Surgical resection after neoadjuvant chemoradiation for oesophageal adenocarcinoma: what is the optimal timing?

OBJECTIVES The purpose of this study was to determine the optimal timing of surgical resection of oesophageal adenocarcinoma following neoadjuvant chemoradiotherapy (nCRT). METHODS nCRT before resection of oesophageal adenocarcinoma yields improved overall and progression‐free survival. Despite the wide acceptance of tri‐modal therapy, the optimal timing of surgical resection after nCRT is not well defined and existing studies are limited. Adults with Stage II/III oesophageal adenocarcinoma undergoing nCRT before surgery were identified from the National Cancer Database. Multivariable analysis using restricted cubic splines was used to identify an inflection point in clinical outcomes as a function of time between nCRT and surgery, dividing the cohort into short‐ and long‐interval treatment groups, which were then compared. Adjusted rates of survival and margin status were compared between groups using multivariable analysis. RESULTS Among 2444 patients, restricted cubic splines identified an inflection point at 56 days, dividing our cohort into 1533 short‐interval and 911 long‐interval patients. Long‐interval patients had a higher adjusted incidence of pathologic downstaging (odds ratio 1.38, confidence interval 1.02‐1.85, P = 0.04) but no difference in margin positivity compared with short‐interval patients (odds ratio 0.91, confidence interval 0.56‐1.47, P = 0.69). Worse overall survival was noted in the long‐interval subgroup (hazard ratio 1.44, confidence interval 1.22‐1.71, P < 0.001), but 30‐day postoperative mortality was not statistically different (odds ratio 1.56, confidence interval 0.9‐2.72, P = 0.12). CONCLUSIONS Restricted cubic splines provides an objective mechanism to more accurately delineate optimum timing between nCRT and surgical resection. A time interval of 56 days represents an interval where increased pathologic downstaging is balanced by decreased overall survival.

Insurance Status, Not Race, is Associated With Use of Minimally Invasive Surgical Approach for Rectal Cancer.

Objective: To determine the impact of race and insurance on use of minimally invasive (MIS) compared with open techniques for rectal cancer in the United States. Background: Race and socioeconomic status have been implicated in disparities of rectal cancer treatment. Methods: Adults undergoing MIS (laparoscopic or robotic) or open rectal resections for stage I to III rectal adenocarcinoma were included from the National Cancer Database (2010–2012). Multivariate analyses were employed to examine the adjusted association of race and insurance with use of MIS versus open surgery. Results: Among 23,274 patients, 39% underwent MIS and 61% open surgery. Overall, 86% were white, 8% black, and 3% Asian. Factors associated with use of open versus MIS were black race, Medicare/Medicaid insurance, and lack of insurance. However, after adjustment for patient demographic, clinical, and treatment characteristics, black race was not associated with use of MIS versus open surgery [odds ratio [OR] 0.90, P = 0.07). Compared with privately insured patients, uninsured patients (OR 0.52, P < 0.01) and those with Medicare/Medicaid (OR 0.79, P < 0.01) were less likely to receive minimally invasive resections. Lack of insurance was significantly associated with less use of MIS in black (OR 0.59, P = 0.02) or white patients (OR 0.51, P < 0.01). However, among uninsured patients, black race was not associated with lower use of MIS (OR 0.96, P = 0.59). Conclusions: Insurance status, not race, is associated with utilization of minimally invasive techniques for oncologic rectal resections. Due to the short-term benefits and cost-effectiveness of minimally invasive techniques, hospitals may need to improve access to these techniques, especially for uninsured patients.

A Risk Score to Assist Selecting Lobectomy Versus Sublobar Resection for Early Stage Non-Small Cell Lung Cancer.

BACKGROUND The long-term survival benefit of lobectomy over sublobar resection for early-stage non-small cell lung cancer must be weighed against a potentially increased risk of perioperative mortality. The objective of the current study was to create a risk score to identify patients with favorable short-term outcomes following lobectomy. METHODS The 2005-2012 American College of Surgeons National Surgical Quality Improvement Program database was queried for patients undergoing a lobectomy or sublobar resection (either segmentectomy or wedge resection) for lung cancer. A multivariable logistic regression model was utilized to determine factors associated with 30-day mortality among the lobectomy group and to develop an associated risk score to predict perioperative mortality. RESULTS Of the 5,749 patients who met study criteria, 4,424 (77%) underwent lobectomy, 1,098 (19%) underwent wedge resection, and 227 (4%) underwent segmentectomy. Age, chronic obstructive pulmonary disease, previous cerebrovascular event, functional status, recent smoking status, and surgical approach (minimally invasive versus open) were utilized to develop the risk score. Patients with a risk score of 5 or lower had no significant difference in perioperative mortality by surgical procedure. Patients with a risk score greater than 5 had significantly higher perioperative mortality after lobectomy (4.9%) as compared to segmentectomy (3.6%) or wedge resection (0.8%, p < 0.01). CONCLUSIONS In this study, we have developed a risk model that predicts relative operative mortality from a sublobar resection as compared to a lobectomy. Among patients with a risk score of 5 or less, lobectomy confers no additional perioperative risk over sublobar resection.

The utility of 6-minute walk distance in predicting waitlist mortality for lung transplant candidates

BACKGROUND The lung allocation score (LAS) has led to improved organ allocation for transplant candidates. At present, the 6-minute walk distance (6MWD) is treated as a binary categorical variable of whether or not a candidate can walk more than 150 feet in 6 minutes. In this study, we tested the hypothesis that 6MWD is presently under-utilized with respect to discriminatory power, and that, as a continuous variable, could better prognosticate risk of waitlist mortality. METHODS A retrospective cohort analysis was performed using the Organ Procurement and Transplantation Network/United Network for Organ Sharing (OPTN/UNOS) transplant database. Candidates listed for isolated lung transplant between May 2005 and December 2011 were included. The population was stratified by 6MWD quartiles and unadjusted survival rates were estimated. Multivariable Cox proportional hazards modeling was used to assess the effect of 6MWD on risk of death. The Scientific Registry of Transplant Recipients (SRTR) Waitlist Risk Model was used to adjust for confounders. The optimal 6MWD for discriminative accuracy in predicting waitlist mortality was assessed by receiver-operating characteristic (ROC) curves. RESULTS Analysis was performed on 12,298 recipients. Recipients were segregated into quartiles by distance walked. Waitlist mortality decreased as 6MWD increased. In the multivariable model, significant variables included 6MWD, male gender, non-white ethnicity and restrictive lung diseases. ROC curves discriminated 6-month mortality was best at 655 feet. CONCLUSIONS The 6MWD is a significant predictor of waitlist mortality. A cut-off of 150 feet sub-optimally identifies candidates with increased risk of mortality. A cut-off between 550 and 655 feet is more optimal if 6MWD is to be treated as a dichotomous variable. Utilization of the LAS as a continuous variable could further enhance predictive capabilities.

Extracorporeal membrane oxygenation following lung transplantation: indications and survival

BACKGROUND Extracorporeal membrane oxygenation (ECMO) is employed to rescue patients with early graft dysfunction after lung transplantation (LTx). Rates of post-LTx ECMO and subsequent outcomes have been limited to single-center reports. METHODS UNOS registry was queried for LTx recipients from March 2015 to March 2016; 2,001 recipients were identified and stratified by need for post-LTx ECMO. Logistic regression was used to determine variables associated with post-LTx ECMO. Cox proportional hazards modeling identified factors associated with survival. Kaplan-Meier analysis with log-rank testing was employed for survival analysis. RESULTS Of 2,001 recipients identified, 107 required post-LTx ECMO (5.1%). Recipients requiring ECMO were younger (56 vs 60 years, p = 0.007) and had higher body mass index (27.2 vs 25.8, p = 0.012). Recipients requiring post-LTx ECMO were more likely to have required mechanical ventilation before transplant (9.3% vs 4.9%, p = 0.049) and were more likely to have required pre-transplant ECMO (15% vs 3.7%, p < 0.001). On multivariable analysis, pre-transplant ECMO and increasing ischemic time were associated with post-LTx ECMO. Six-month survival for recipients requiring ECMO was 62.2%. On multivariable analysis, need for post-transplant dialysis was associated with mortality. Six-month survival for recipients requiring ECMO with and without dialysis was 25.8% and 86.7% (p < 0.001). CONCLUSIONS In a nationally representative database, ischemic time and pre-transplant ECMO and/or ventilator requirement were associated with need for post-LTx ECMO. Need for post-transplant dialysis was associated with mortality in patients requiring post-LTx ECMO. These data may permit improved prediction of graft dysfunction. Strategies to minimize renal toxicity in the perioperative phase may lead to improved early survival post-LTx.

Outcomes of Reoperation After Acute Type A Aortic Dissection: Implications for Index Repair Strategy.

Background The optimal surgical approach for management of acute type A aortic dissection remains controversial. This study aimed to assess outcomes of reoperation after acute type A dissection repair to help guide decision making around index operative strategy. Methods and Results All aortic reoperations (n=129) at a single referral institution from August 2005 to April 2016 after prior acute type A dissection repair were reviewed. The primary outcome was 30‐day or in‐hospital mortality. Secondary outcomes included organ‐specific morbidity and 1‐ and 5‐year outcomes as estimated using the Kaplan–Meier method. The majority of initial reoperations were proximal aortic (aortic valve, aortic root, or ascending) or aortic arch procedures (62.5%, n=55); most initial reoperations were performed in the elective setting (83.1%, n=74). Additional nonstaged second or more reoperations were required in 21 patients (23.6%) after the initial reoperation, during a median follow‐up of 2.5 years after the initial reoperation. Thirty‐day or in‐hospital mortality for all reoperations was 7.0% (elective: 6.3%; nonelective: 11.1%) with acceptable rates of organ‐specific morbidity, given the procedural complexity. One‐ and 5‐year overall survival after initial reoperation was 85.9% and 64.9%, respectively, with aorta‐specific survival of 88% at 5 years. Conclusions Reoperation after acute type A aortic dissection repair is associated with low rates of mortality and morbidity. These data support more limited index repair for acute type A dissection, especially for patients undergoing index repair in lower volume centers without expertise in extensive repair, because reoperations, if needed, can be performed safely in referral aortic centers.