Cancer of the esophagus and esophagogastric junction-Major changes in the American Joint Committee on Cancer eighth edition cancer staging manual.

Answer questions and earn CME/CNE New to the eighth edition of the American Joint Committee on Cancer (AJCC) Cancer Staging Manual for epithelial cancers of the esophagus and esophagogastric junction are separate, temporally related cancer classifications: 1) before treatment decision (clinical); 2) after esophagectomy alone (pathologic); and 3) after preresection therapy followed by esophagectomy (postneoadjuvant pathologic). The addition of clinical and postneoadjuvant pathologic stage groupings was driven by a lack of correspondence of survival, and thus prognosis, between both clinical and postneoadjuvant pathologic cancer categories (facts about the cancer) and pathologic categories. This was revealed by a machine-learning analysis of 6-continent data from the Worldwide Esophageal Cancer Collaboration, with consensus of the AJCC Upper GI Expert Panel. Survival is markedly affected by histopathologic cell type (squamous cell carcinoma and adenocarcinoma) in clinically and pathologically staged patients, requiring separate stage grouping for each cell type. However, postneoadjuvant pathologic stage groups are identical. For the future, more refined and granular data are needed. This requires: 1) more accurate clinical staging; 2) innovative solutions to pathologic staging challenges in endoscopically resected cancers; 3) integration of genomics into staging; and 4) precision cancer care with targeted therapy. It is the responsibility of the oncology team to accurately determine and record registry data, which requires eliminating both common errors and those related to incompleteness and inconsistency. Despite the new complexity of eighth edition staging of cancers of the esophagus and esophagogastric junction, these key concepts and new directions will facilitate precision cancer care. CA Cancer J Clin 2017;67:304-317. © 2017 American Cancer Society.

How Much Delay Matters? How Time to Treatment Impacts Overall Survival in Early Stage Lung Cancer.

OBJECTIVES: The aim of this study was to identify drivers of time from diagnosis to treatment (TTT) of surgically resected early stage non-small cell lung cancer (NSCLC) and determine the effect of TTT on post-resection survival. SUMMARY BACKGROUND DATA: Large database studies that lack relevant comorbidity data have identified longer TTT asa driver of worse overall survival. METHODS: From January 1, 2014 to April 1, 2018, 599 patients underwent lung resection for clinical stage I and II NSCLC. Random forest classification, regression, and survival were used to estimate likelihood of TTT = 0 (tissue diagnosis obtained at surgery), >0 (diagnosis obtained pre-resection), and effect of TTT on all-cause mortality. RESULTS: Patients with TTT > 0 (n = 413) had median TTT of 42 days (25-75 th percentile: 27-59 days). Patients with TTT = 0 (n = 186) had smaller tumors and higher percent predicted forced expiratory volume in 1 second (FEV 1 %). Patients with history of stroke, oncology consultation, invasive mediastinal staging, low and high extremes of FEV 1 % had longer TTT. Higher clinical stage, lack of preoperative stress test, anemia, older age, lower FEV1% and diffusion lung capacity, larger tumor size, and longer TTT were the most important predictors of all-cause mortality. One- and 5-year overall survival decreased when TTT was >50 days. CONCLUSIONS: Preoperative physiologic workup and multidisciplinary evaluation were the predominant drivers of longer TTT. Patients with TTT = 0have more favorable presentation and should be considered in TTT analyses for early stage lung cancer populations. The time needed to clinically stage and optimize patients for resection is not deleterious to overall survival until resection is performed after 50 days from diagnosis.

Adjuvant Therapy After Neoadjuvant Therapy for Esophageal Cancer: Who Needs It?

OBJECTIVE: We hypothesized that, on average, patients do not benefit from additional adjuvant therapy after neoadjuvant therapy for locally advanced esophageal cancer, although subsets of patients might. Therefore, we sought to identify profiles of patients predicted to receive the most survival benefit or greatest detriment from adding adjuvant therapy. BACKGROUND: Although neoadjuvant therapy has become the treatment of choice for locally advanced esophageal cancer, the value of adding adjuvant therapy is unknown. METHODS: From 1970 to 2014, 22,123 patients were treated for esophageal cancer at 33 centers on 6 continents (Worldwide Esophageal Cancer Collaboration), of whom 7731 with adenocarcinoma or squamous cell carcinoma received neoadjuvant therapy; 1348 received additional adjuvant therapy. Random forests for survival and virtual-twin analyses were performed for all-cause mortality. RESULTS: Patients received a small survival benefit from adjuvant therapy (3.2±10 months over the subsequent 10 years for adenocarcinoma, 1.8±11 for squamous cell carcinoma). Consistent benefit occurred in ypT3-4 patients without nodal involvement and those with ypN2-3 disease. The small subset of patients receiving most benefit had high nodal burden, ypT4, and positive margins. Patients with ypT1-2N0 cancers had either no benefit or a detriment in survival. CONCLUSIONS: Adjuvant therapy after neoadjuvant therapy has value primarily for patients with more advanced esophageal cancer. Because the benefit is often small, patients considering adjuvant therapy should be counseled on benefits versus morbidity. In addition, given that the overall benefit was meaningful in a small number of patients, emerging modalities such as immunotherapy may hold more promise in the adjuvant setting.

Quantifying the subjective: length-to-height ratio characterizes achalasia esophageal tortuosity.

BACKGROUND: Esophageal morphology in achalasia is thought to affect outcomes, with "end-stage" sigmoidal morphology faring poorly; however, evaluation of morphology's role in outcomes has been limited by lack of objective characterization. Hence, the goals of this study were twofold: characterize the variability of timed barium esophagram (TBE) interpretation and evaluate an objective classification of TBE tortuosity: length-to-height ratio (LHR). We hypothesized that the esophagus must elongate to become sigmoidal such that sigmoidal morphology would demonstrate a larger LHR. METHODS: Ninety pre-operative TBEs were selected from an institutional database. Esophageal morphology was categorized as straight, intermediate, or sigmoidal. Esophageal length was measured by a mid-lumen line from the aortic knob to the esophagogastric junction on TBE; height was measured vertically from the aortic knob to the level of the esophagogastric junction. The length divided by the height generated the LHR. Descriptive statistics and frequency of expert agreement were calculated. Median LHR was compared between consensus morphologies. A receiver operating characteristic (ROC) determined the optimal LHR for sigmoidal vs non-sigmoidal characterization. RESULTS: From a total of 90 pre-operative TBEs, expert consensus morphology was reached in 56 (62.2%) cases. Pairs of experts agreed on morphology in 62-74% of TBEs, with all three experts agreeing on 46.7-48.9% of cases. Median LHR between expert consensus morphologies was 1.03, 1.09, and 1.24 for straight, intermediate, and sigmoidal morphologies, respectively (p < 0.001). ROC demonstrated that an LHR cutoff of 1.13 was 100% sensitive and 95% specific (AUC 0.99) for ruling out sigmoidal morphology. CONCLUSION: These findings confirm our anecdotal experience that subjective morphology interpretation is variable, even between experts at a high-volume center. LHR provides an objective method for classification, allowing us to overcome the limitations of inter-observer variability, thus paving the way for future study of the role of morphology in achalasia outcomes.

Effectiveness and Safety of E-aminocaproic Acid in Overall and Less-Invasive Cardiac Surgeries.

OBJECTIVES: To examine E-aminocaproic acid effectiveness in reducing transfusion requirements in overall and less-invasive cardiac surgery, and to assess its safety. DESIGN: Retrospective cohort study. SETTING: Single-center tertiary academic medical center. PARTICIPANTS: A total of 19,111 adult patients who underwent elective surgery requiring cardiopulmonary bypass from January 1, 2008, through December 31, 2016. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Propensity matching was used to create well-balanced groups and separately compare both overall cohort and less-invasive surgery with and without E-aminocaproic acid. Supplementary zero-inflated negative binomial regression analysis was used because outcome data were zero-inflated. Effectiveness was assessed by transfusion requirements, and safety by comparison of in-hospital outcomes. In the overall cohort, patients receiving E-aminocaproic acid received fewer red blood cells postoperatively and fewer intra- and postoperativel blood products. In a less-invasive cohort, there was no significant difference in red blood cell transfusion either intra- or postoperatively, but the E-aminocaproic group received fewer intra- and postoperative platelets, intraoperative cryoprecipitate, and postoperative plasma. There were no significant differences for in-hospital outcomes in both less-invasive and overall cohorts. CONCLUSIONS: The reduction of postoperative red blood cell requirement observed when analyzing the overall cohort did not translate to less-invasive cardiac surgery in the authors' patient population; however, both overall and less-invasive cohorts had lower requirements for other blood components with E-aminocaproic acid. There was no association with major Society of thoracic surgeons (STS)-defined morbidity and mortality in both groups.

Valve Academic Research Consortium 3: updated endpoint definitions for aortic valve clinical research.

AIMS: The Valve Academic Research Consortium (VARC), founded in 2010, was intended to (i) identify appropriate clinical endpoints and (ii) standardize definitions of these endpoints for transcatheter and surgical aortic valve clinical trials. Rapid evolution of the field, including the emergence of new complications, expanding clinical indications, and novel therapy strategies have mandated further refinement and expansion of these definitions to ensure clinical relevance. This document provides an update of the most appropriate clinical endpoint definitions to be used in the conduct of transcatheter and surgical aortic valve clinical research. METHODS AND RESULTS: Several years after the publication of the VARC-2 manuscript, an in-person meeting was held involving over 50 independent clinical experts representing several professional societies, academic research organizations, the US Food and Drug Administration (FDA), and industry representatives to (i) evaluate utilization of VARC endpoint definitions in clinical research, (ii) discuss the scope of this focused update, and (iii) review and revise specific clinical endpoint definitions. A writing committee of independent experts was convened and subsequently met to further address outstanding issues. There were ongoing discussions with FDA and many experts to develop a new classification schema for bioprosthetic valve dysfunction and failure. Overall, this multi-disciplinary process has resulted in important recommendations for data reporting, clinical research methods, and updated endpoint definitions. New definitions or modifications of existing definitions are being proposed for repeat hospitalizations, access site-related complications, bleeding events, conduction disturbances, cardiac structural complications, and bioprosthetic valve dysfunction and failure (including valve leaflet thickening and thrombosis). A more granular 5-class grading scheme for paravalvular regurgitation (PVR) is being proposed to help refine the assessment of PVR. Finally, more specific recommendations on quality-of-life assessments have been included, which have been targeted to specific clinical study designs. CONCLUSIONS: Acknowledging the dynamic and evolving nature of less-invasive aortic valve therapies, further refinements of clinical research processes are required. The adoption of these updated and newly proposed VARC-3 endpoints and definitions will ensure homogenous event reporting, accurate adjudication, and appropriate comparisons of clinical research studies involving devices and new therapeutic strategies.

Value of Lymphadenectomy in Patients Receiving Neoadjuvant Therapy for Esophageal Adenocarcinoma.

OBJECTIVE: The aim of this study was to assess the effect on survival of extent of lymphadenectomy during esophagectomy for patients undergoing multimodality (neoadjuvant) therapy for adenocarcinoma of the esophagus and esophagogastric junction using Worldwide Esophageal Cancer Collaboration data. SUMMARY BACKGROUND DATA: Previous worldwide data demonstrated that optimum lymphadenectomy during esophagectomy alone for esophageal cancer provides accurate staging and maximum survival. However, for patients undergoing neoadjuvant therapy for locally advanced adenocarcinoma, its value is unclear, leading to wide practice variability. METHODS: A total of 3859 patients with adenocarcinoma of the esophagus or esophagogastric junction received neoadjuvant therapy. The endpoint was all-cause mortality, reported as gain or loss of lifetime within 10 years. Lifetime predicted for each regional lymph node resected used quantile survival random forest methodology. RESULTS: Across all post-neoadjuvant ypTNM cancer categories, some degree of lymphadenectomy was associated with longer lifetime, but in a nonlinear fashion. For patients with ypN0 cancers, there was a modest gain in lifetime up to 25 lymph nodes resected and an incremental loss in lifetime as >25 were resected. For patients with ypN+ cancers, there was a robust gain in lifetime up to 30 lymph nodes resected and then an incremental loss in lifetime. CONCLUSIONS: Worldwide data for adenocarcinoma of the esophagus and esophagogastric junction demonstrate that lymphadenectomy during esophagectomy is a valuable component of neoadjuvant therapy. Survival is maximized when an optimum range of nodes is resected.

Repair, Reconstruct, or Divert: Fate of the Perforated Esophagus.

OBJECTIVES: The aim of this study was to determine differences in esophageal perforation populations undergoing different advanced interventions for perforated esophagus and identify predictors of treatment outcomes. SUMMARY BACKGROUND DATA: Contained esophageal perforation can often be managed expectantly, but uncontained perforation is uniformly fatal without invasive intervention. Treatment options for the latter range from simple endoscopic control through advanced intervention. Clinical presentation varies greatly and directs which intervention is most appropriate. METHODS: From 1996 to 2017, 335 patients were treated for esophageal perforation, and 166 for advanced interventions: 74 primary repair with tissue flap (repair), 26 esophagectomy and gastric pull-up (resection), and 66 esophagectomy and immediate diversion with planned delayed reconstruction (resection-diversion). Patient characteristics, clinical presentation, operative outcomes, and survival were abstracted. Pittsburgh Severity Scores (PSS) were retrospectively calculated. Random survival forest analysis was performed for 90-day mortality and competing risks for reconstruction after resection-diversion. RESULTS: Repair and resection patients had lower PSS than resection-diversion patients (3 vs 3 vs 6, respectively). Ninety-day mortality for repair, resection, and resection-diversion was 11% vs 7.7% vs 23%, and 5-year survival was 71% vs 63% vs 47%. Risk of death after resection-diversion was highest within 1 year, but 52% of patients had reconstruction of the upper alimentary tract within 2 years. CONCLUSIONS: Several advanced interventions exist for critically ill patients with uncontained esophageal perforation. Repair and organ preservation are always preferred; however, patients at extremes of illness might best be treated with resection-diversion, with the understanding that the competing risk of death may preclude eventual reconstruction.

Rationale and design of PROACT Xa: A randomized, multicenter, open-label, clinical trial to evaluate the efficacy and safety of apixaban versus warfarin in patients with a mechanical On-X Aortic Heart Valve.

Vitamin K antagonists are the only approved oral anticoagulants for long-term prophylaxis against valve thrombosis and thromboembolism in patients with a mechanical heart valve. Despite the proven efficacy and safety of anticoagulation with the oral direct factor Xa inhibitor apixaban compared with warfarin in high-risk populations including subjects with atrial fibrillation or with venous thromboembolism, it remains unknown whether patients with a mechanical heart valve can be safely managed with apixaban. The On-X Aortic Heart Valve and On-X Ascending Aortic Prosthesis with the Vascutek Gelweave Valsalva Graft may have lower rates of valve thrombosis and thromboembolism than conventional bileaflet and tilting disc valves due its unique pyrolytic carbon composition and flared inlet design. DESIGN: PROACT Xa is a randomized, multicenter, open-label, active-controlled trial comparing apixaban with warfarin in patients with an On-X Aortic Heart Valve or On-X Ascending Aortic Prosthesis with the Vascutek Gelweave Valsalva Graft. The study will randomize approximately 1,000 patients from approximately 60 sites in North America who underwent aortic valve replacement at least 3 months prior. Patients will be randomized 1:1 to receiving apixaban 5 mg twice daily or warfarin with a target international normalized ratio of 2.0-3.0. The last randomized participant will be followed for at least 2 years. The primary efficacy outcome is the composite of valve thrombosis and valve-related thromboembolism, and the primary safety outcome is major bleeding. Assuming the primary outcome occurs in warfarin-anticoagulated patients at a rate of 1.75%/patient-year, the study has more than 90% power to assess noninferiority of apixaban treatment with an absolute noninferiority margin of 1.75%/patient-year. A second co-primary analysis is to compare the hazard rate for the apixaban arm to twice the objective performance criterion for thromboembolism and valve thrombosis, that is, 3.4%/patient-year. SUMMARY: PROACT Xa will determine whether patients with an On-X Aortic Heart Valve can be anticoagulated with apixaban as an alternative to warfarin.

Coronary Artery Bypass Graft Patency and Survival in Patients on Dialysis.

BACKGROUND: Little is known about graft patency after coronary artery bypass grafting (CABG) performed in patients on dialysis. Our aim was to assess patency of internal thoracic artery (ITA) grafts and saphenous vein grafts (SVGs) in these patients. METHODS: From 1/1997 to 1/2018, 500 patients on dialysis underwent primary CABG with or without concomitant procedures at Cleveland Clinic, 40 of whom had 48 postoperative angiograms for recurrent ischemic symptoms. Complete follow-up was obtained on all but 1 patient lost to follow-up 1 y after CABG. Thirty-six ITA grafts and 65 SVGs were evaluable for stenosis and occlusion. RESULTS: Two of 40 patients (5%) had emergency CABG; 3 (7.5%) with calcified aortas had a change in operative strategy to avoid ascending aortic manipulation, 2 (5%) had poor conduit quality, and 12 (30%) had severe diffuse atherosclerotic disease with calcification of the coronary targets causing technical difficulties. Thirty-three patients (82%) were bypassed with an in situ ITA and 3 (7.5%) had a free ITA graft. Three of 36 ITA grafts were occluded at 0.78, 1.8, and 9.4 y (too few to model). SVG patency was 52% and 37% at 1 and 2 y, respectively. CONCLUSIONS: Among patients on dialysis who underwent CABG, coronary angiography for ischemic symptoms in a select subset revealed that SVG patency was lower than expected from published reports in the general CABG population and may contribute to the poor prognosis of this cohort. Further work is needed to guide graft selection and improve graft patency in dialysis patients.

Variables of importance in the Scientific Registry of Transplant Recipients database predictive of heart transplant waitlist mortality.

The prelisting variables essential for creating an accurate heart transplant allocation score based on survival are unknown. To identify these we studied mortality of adults on the active heart transplant waiting list in the Scientific Registry of Transplant Recipients database from January 1, 2004 to August 31, 2015. There were 33 069 candidates awaiting heart transplantation: 7681 UNOS Status 1A, 13 027 Status 1B, and 12 361 Status 2. During a median waitlist follow-up of 4.3 months, 5514 candidates died. Variables of importance for waitlist mortality were identified by machine learning using Random Survival Forests. Strong correlates predicting survival were estimated glomerular filtration rate (eGFR), serum albumin, extracorporeal membrane oxygenation, ventricular assist device, mechanical ventilation, peak oxygen capacity, hemodynamics, inotrope support, and type of heart disease with less predictive variables including antiarrhythmic agents, history of stroke, vascular disease, prior malignancy, and prior tobacco use. Complex interactions were identified such as an additive risk in mortality based on renal function and serum albumin, and sex-differences in mortality when eGFR >40 mL/min/1.73 m. Most predictive variables for waitlist mortality are in the current tiered allocation system except for eGFR and serum albumin which have an additive risk and complex interactions.

Hemodynamic durability of transcatheter aortic valves using the updated Valve Academic Research Consortium-2 criteria.

OBJECTIVES: We investigated the hemodynamic durability of the transcatheter aortic valves (TAVs) using the updated Valve Academic Research Consortium-2 (VARC-2) criteria. BACKGROUND: The updated VARC-2 consensus criteria combine flow-dependent and flow-independent echocardiographic parameters for hemodynamic assessment of TAVR. Data on the hemodynamic durability of TAV and clinical risk factors associated with valve hemodynamic deterioration (VHD) are lacking. METHODS: All patients (n = 276) who received TAV between 2006 and 2012 and had ≥2 follow-up echocardiograms were studied. RESULTS: During a median follow up period of 3.3 (1.8-4.4) years, 8 patients (3%) developed moderate to severe valve stenosis per the VARC-2 criteria, while 20 had mild stenosis. In a Cox proportional hazards model analysis, moderate to severe stenosis by VARC-2 criteria was associated with younger age (P = 0.03, HR 0.94), absence of dual antiplatelet therapy (DAPT) (P = 0.026, HR 0.18), and lower baseline left ventricular ejection fraction (LVEF) (P = 0.006, HR 0.94). Longitudinal analysis using a mixed effect model showed that presence of stenosis by VARC-2 criteria was associated with an increase in aortic valve mean gradient (P < 0.001, +2.34 mmHg per year). In a subset of 93 patients with analyzable fluoroscopic images, deeper valve implantation was associated with increase in mean gradient (P = 0.004, +0.2 mmHg per year per 1 mm increase in implantation depth). CONCLUSION: Despite good hemodynamic durability of TAV, patients with younger age, lower LVEF and those not on DAPT after undergoing a TAV replacement, are at a higher risk for development of VHD.

The Optimal Timing of Stage 2 Palliation for Hypoplastic Left Heart Syndrome: An Analysis of the Pediatric Heart Network Single Ventricle Reconstruction Trial Public Data Set.

BACKGROUND: In infants requiring 3-stage single-ventricle palliation for hypoplastic left heart syndrome, attrition after the Norwood procedure remains significant. The effect of the timing of stage 2 palliation (S2P), a physician-modifiable factor, on long-term survival is not well understood. We hypothesized that an optimal interval between the Norwood and S2P that both minimizes pre-S2P attrition and maximizes post-S2P survival exists and is associated with individual patient characteristics. METHODS: The National Institutes of Health/National Heart, Lung, and Blood Institute Pediatric Heart Network Single Ventricle Reconstruction Trial public data set was used. Transplant-free survival (TFS) was modeled from (1) Norwood to S2P and (2) S2P to 3 years by using parametric hazard analysis. Factors associated with death or heart transplantation were determined for each interval. To account for staged procedures, risk-adjusted, 3-year, post-Norwood TFS (the probability of TFS at 3 years given survival to S2P) was calculated using parametric conditional survival analysis. TFS from the Norwood to S2P was first predicted. TFS after S2P to 3 years was then predicted and adjusted for attrition before S2P by multiplying by the estimate of TFS to S2P. The optimal timing of S2P was determined by generating nomograms of risk-adjusted, 3-year, post-Norwood, TFS versus the interval from the Norwood to S2P. RESULTS: Of 547 included patients, 399 survived to S2P (73%). Of the survivors to S2P, 349 (87%) survived to 3-year follow-up. The median interval from the Norwood to S2P was 5.1 (interquartile range, 4.1-6.0) months. The risk-adjusted, 3-year, TFS was 68±7%. A Norwood-S2P interval of 3 to 6 months was associated with greatest 3-year TFS overall and in patients with few risk factors. In patients with multiple risk factors, TFS was severely compromised, regardless of the timing of S2P and most severely when S2P was performed early. No difference in the optimal timing of S2P existed when stratified by shunt type. CONCLUSIONS: In infants with few risk factors, progressing to S2P at 3 to 6 months after the Norwood procedure was associated with maximal TFS. Early S2P did not rescue patients with greater risk factor burdens. Instead, referral for heart transplantation may offer their best chance at long-term survival. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00115934.

Surgical ablation of atrial fibrillation during mitral-valve surgery.

BACKGROUND: Among patients undergoing mitral-valve surgery, 30 to 50% present with atrial fibrillation, which is associated with reduced survival and increased risk of stroke. Surgical ablation of atrial fibrillation has been widely adopted, but evidence regarding its safety and effectiveness is limited. METHODS: We randomly assigned 260 patients with persistent or long-standing persistent atrial fibrillation who required mitral-valve surgery to undergo either surgical ablation (ablation group) or no ablation (control group) during the mitral-valve operation. Patients in the ablation group underwent further randomization to pulmonary-vein isolation or a biatrial maze procedure. All patients underwent closure of the left atrial appendage. The primary end point was freedom from atrial fibrillation at both 6 months and 12 months (as assessed by means of 3-day Holter monitoring). RESULTS: More patients in the ablation group than in the control group were free from atrial fibrillation at both 6 and 12 months (63.2% vs. 29.4%, P<0.001). There was no significant difference in the rate of freedom from atrial fibrillation between patients who underwent pulmonary-vein isolation and those who underwent the biatrial maze procedure (61.0% and 66.0%, respectively; P=0.60). One-year mortality was 6.8% in the ablation group and 8.7% in the control group (hazard ratio with ablation, 0.76; 95% confidence interval, 0.32 to 1.84; P=0.55). Ablation was associated with more implantations of a permanent pacemaker than was no ablation (21.5 vs. 8.1 per 100 patient-years, P=0.01). There were no significant between-group differences in major cardiac or cerebrovascular adverse events, overall serious adverse events, or hospital readmissions. CONCLUSIONS: The addition of atrial fibrillation ablation to mitral-valve surgery significantly increased the rate of freedom from atrial fibrillation at 1 year among patients with persistent or long-standing persistent atrial fibrillation, but the risk of implantation of a permanent pacemaker was also increased. (Funded by the National Institutes of Health and the Canadian Institutes of Health Research; ClinicalTrials.gov number, NCT00903370.).

Survival affects decision making for fenestrated and branched endovascular aortic repair.

OBJECTIVE: Repair options for complex abdominal and thoracoabdominal aortic aneurysms (TAAAs) are evolving with increased experience and availability of less invasive endovascular techniques. Identifying risk factors for mortality after fenestrated and branched endovascular aortic repair (F/B-EVAR) could improve patient selection and facilitate decision making regarding who may benefit from prophylactic F/B-EVAR. METHODS: We evaluated 1091 patients in a prospective investigational device exemption trial who underwent F/B-EVAR from August 2001 to June 2015 for complex aortic aneurysms (CAAs). Multivariable analysis of risk factors for death was performed using a nonproportional hazards model and a nonparametric analysis using random survival forest technology. RESULTS: Operative mortality after F/B-EVAR was low (3.7%), with high CAA-related survival at 30 day and 5 years (96.8% and 94.0%, respectively). All-cause 5-year survival, however, was 46.2% and older age, heart failure, chronic obstructive pulmonary disease, renal disease, anemia, and coagulation disorders were risk factors. Risk was highest for those undergoing type I/II TAAA repairs and those with larger aneurysms. CONCLUSIONS: Patients with multiple comorbidities and those undergoing type I or II TAAA repair are at greatest risk of mortality; however, in this high-risk population, F/B-EVAR offers greater survival compared with that reported for the natural history of untreated aneurysms. Operative and early mortality is lower than the best-reported open repair outcomes, even in this high-risk population, suggesting a potential benefit in extending the use of F/B-EVAR to low-to-average risk CAA patients.

Bretschneider and del Nido solutions: Are they safe for coronary artery bypass grafting? If so, how should we use them?

A variety of cardioplegic solutions are being used widely today to arrest the heart during coronary artery bypass grafting (CABG) and other cardiac operations. To minimize interruptions during the surgery for intermittent dosing of the cardioplegia and to facilitate less invasive cardiac procedures, single-shot solutions, including Bretschneider and del Nido solutions, have been introduced. This review examines the evidence regarding the safety and efficacy of Bretschneider and del Nido cardioplegia during CABG. The findings support their use in routine low-risk CABG, but finds insufficient evidence to support their safety in high-risk surgeries.

Esophageal Cancer: Associations With (pN+) Lymph Node Metastases.

OBJECTIVES: To identify the associations of lymph node metastases (pN+), number of positive nodes, and pN subclassification with cancer, treatment, patient, geographic, and institutional variables, and to recommend extent of lymphadenectomy needed to accurately detect pN+ for esophageal cancer. SUMMARY BACKGROUND DATA: Limited data and traditional analytic techniques have precluded identifying intricate associations of pN+ with other cancer, treatment, and patient characteristics. METHODS: Data on 5806 esophagectomy patients from the Worldwide Esophageal Cancer Collaboration were analyzed by Random Forest machine learning techniques. RESULTS: pN+, number of positive nodes, and pN subclassification were associated with increasing depth of cancer invasion (pT), increasing cancer length, decreasing cancer differentiation (G), and more regional lymph nodes resected. Lymphadenectomy necessary to accurately detect pN+ is 60 for shorter, well-differentiated cancers (<2.5 cm) and 20 for longer, poorly differentiated ones. CONCLUSIONS: In esophageal cancer, pN+, increasing number of positive nodes, and increasing pN classification are associated with deeper invading, longer, and poorly differentiated cancers. Consequently, if the goal of lymphadenectomy is to accurately define pN+ status of such cancers, few nodes need to be removed. Conversely, superficial, shorter, and well-differentiated cancers require a more extensive lymphadenectomy to accurately define pN+ status.

Unexpected abrupt increase in left ventricular assist device thrombosis.

BACKGROUND: We observed an apparent increase in the rate of device thrombosis among patients who received the HeartMate II left ventricular assist device, as compared with preapproval clinical-trial results and initial experience. We investigated the occurrence of pump thrombosis and elevated lactate dehydrogenase (LDH) levels, LDH levels presaging thrombosis (and associated hemolysis), and outcomes of different management strategies in a multi-institutional study. METHODS: We obtained data from 837 patients at three institutions, where 895 devices were implanted from 2004 through mid-2013; the mean (±SD) age of the patients was 55±14 years. The primary end point was confirmed pump thrombosis. Secondary end points were confirmed and suspected thrombosis, longitudinal LDH levels, and outcomes after pump thrombosis. RESULTS: A total of 72 pump thromboses were confirmed in 66 patients; an additional 36 thromboses in unique devices were suspected. Starting in approximately March 2011, the occurrence of confirmed pump thrombosis at 3 months after implantation increased from 2.2% (95% confidence interval [CI], 1.5 to 3.4) to 8.4% (95% CI, 5.0 to 13.9) by January 1, 2013. Before March 1, 2011, the median time from implantation to thrombosis was 18.6 months (95% CI, 0.5 to 52.7), and from March 2011 onward, it was 2.7 months (95% CI, 0.0 to 18.6). The occurrence of elevated LDH levels within 3 months after implantation mirrored that of thrombosis. Thrombosis was presaged by LDH levels that more than doubled, from 540 IU per liter to 1490 IU per liter, within the weeks before diagnosis. Thrombosis was managed by heart transplantation in 11 patients (1 patient died 31 days after transplantation) and by pump replacement in 21, with mortality equivalent to that among patients without thrombosis; among 40 thromboses in 40 patients who did not undergo transplantation or pump replacement, actuarial mortality was 48.2% (95% CI, 31.6 to 65.2) in the ensuing 6 months after pump thrombosis. CONCLUSIONS: The rate of pump thrombosis related to the use of the HeartMate II has been increasing at our centers and is associated with substantial morbidity and mortality.

Surgical treatment of moderate ischemic mitral regurgitation.

BACKGROUND: Ischemic mitral regurgitation is associated with increased mortality and morbidity. For surgical patients with moderate regurgitation, the benefits of adding mitral-valve repair to coronary-artery bypass grafting (CABG) are uncertain. METHODS: We randomly assigned 301 patients with moderate ischemic mitral regurgitation to CABG alone or CABG plus mitral-valve repair (combined procedure). The primary end point was the left ventricular end-systolic volume index (LVESVI), a measure of left ventricular remodeling, at 1 year. This end point was assessed with the use of a Wilcoxon rank-sum test in which deaths were categorized as the lowest LVESVI rank. RESULTS: At 1 year, the mean LVESVI among surviving patients was 46.1±22.4 ml per square meter of body-surface area in the CABG-alone group and 49.6±31.5 ml per square meter in the combined-procedure group (mean change from baseline, -9.4 and -9.3 ml per square meter, respectively). The rate of death was 6.7% in the combined-procedure group and 7.3% in the CABG-alone group (hazard ratio with mitral-valve repair, 0.90; 95% confidence interval, 0.38 to 2.12; P=0.81). The rank-based assessment of LVESVI at 1 year (incorporating deaths) showed no significant between-group difference (z score, 0.50; P=0.61). The addition of mitral-valve repair was associated with a longer bypass time (P<0.001), a longer hospital stay after surgery (P=0.002), and more neurologic events (P=0.03). Moderate or severe mitral regurgitation was less common in the combined-procedure group than in the CABG-alone group (11.2% vs. 31.0%, P<0.001). There were no significant between-group differences in major adverse cardiac or cerebrovascular events, deaths, readmissions, functional status, or quality of life at 1 year. CONCLUSIONS: In patients with moderate ischemic mitral regurgitation, the addition of mitral-valve repair to CABG did not result in a higher degree of left ventricular reverse remodeling. Mitral-valve repair was associated with a reduced prevalence of moderate or severe mitral regurgitation but an increased number of untoward events. Thus, at 1 year, this trial did not show a clinically meaningful advantage of adding mitral-valve repair to CABG. Longer-term follow-up may determine whether the lower prevalence of mitral regurgitation translates into a net clinical benefit. (Funded by the National Institutes of Health and the Canadian Institutes of Health Research; ClinicalTrials.gov number, NCT00806988.).

Mitral-valve repair versus replacement for severe ischemic mitral regurgitation.

BACKGROUND: Ischemic mitral regurgitation is associated with a substantial risk of death. Practice guidelines recommend surgery for patients with a severe form of this condition but acknowledge that the supporting evidence for repair or replacement is limited. METHODS: We randomly assigned 251 patients with severe ischemic mitral regurgitation to undergo either mitral-valve repair or chordal-sparing replacement in order to evaluate efficacy and safety. The primary end point was the left ventricular end-systolic volume index (LVESVI) at 12 months, as assessed with the use of a Wilcoxon rank-sum test in which deaths were categorized below the lowest LVESVI rank. RESULTS: At 12 months, the mean LVESVI among surviving patients was 54.6±25.0 ml per square meter of body-surface area in the repair group and 60.7±31.5 ml per square meter in the replacement group (mean change from baseline, -6.6 and -6.8 ml per square meter, respectively). The rate of death was 14.3% in the repair group and 17.6% in the replacement group (hazard ratio with repair, 0.79; 95% confidence interval, 0.42 to 1.47; P=0.45 by the log-rank test). There was no significant between-group difference in LVESVI after adjustment for death (z score, 1.33; P=0.18). The rate of moderate or severe recurrence of mitral regurgitation at 12 months was higher in the repair group than in the replacement group (32.6% vs. 2.3%, P<0.001). There were no significant between-group differences in the rate of a composite of major adverse cardiac or cerebrovascular events, in functional status, or in quality of life at 12 months. CONCLUSIONS: We observed no significant difference in left ventricular reverse remodeling or survival at 12 months between patients who underwent mitral-valve repair and those who underwent mitral-valve replacement. Replacement provided a more durable correction of mitral regurgitation, but there was no significant between-group difference in clinical outcomes. (Funded by the National Institutes of Health and the Canadian Institutes of Health; ClinicalTrials.gov number, NCT00807040.).