Angela Mahan

Identification of patients with postoperative complications who are at risk for failure to rescue.

IMPORTANCE A minority of patients who experience postoperative complications die (failure to rescue). Understanding the preoperative factors that lead to failure to rescue helps surgeons predict and avoid operative mortality. OBJECTIVE To provide a mechanism for identifying a high-risk group of patients with postoperative complications who are at a substantially increased risk for failure to rescue. DESIGN, SETTING, AND PATIENTS Observational study evaluating failure to rescue in patients entered into the American College of Surgeons National Surgical Quality Improvement Program database. The large sample of surgical patients included in this study underwent a wide range of operations during a 5-year period in more than 200 acute care hospitals. We examined and identified patients at high risk for failure to rescue using propensity stratification. We also developed a risk-scoring system that allowed preoperative identification of patients at the highest risk for failure to rescue. MAIN OUTCOMES AND MEASURES Risk-scoring system that predicts failure to rescue. RESULTS Of the 1,956,002 database patients, there were 207,236 patients who developed serious postoperative complications. Deaths occurred in 21,731 patients with serious complications (10.5% failure to rescue). Stratification of patients into quintiles, according to their propensity for developing serious complications, found that 90% of operative deaths occurred in the highest-risk quintile, usually within a week of developing the initial complication. A risk-scoring system for failure to rescue, based on regression-derived variable odds ratios, predicted patients in the highest-risk quintile with good predictive accuracy. Only 31.8% of failure-to-rescue patients had a single postoperative complication. Perioperative deaths increased exponentially as the number of complications per patient increased. Patients with complications who had surgical residents involved in their care had reduced rates of failure to rescue compared with patients without resident involvement. CONCLUSIONS AND RELEVANCE Twenty percent of high-risk patients account for 90% of failure to rescue (Pareto principle). More than two-thirds of patients with failure to rescue have multiple complications. On average, a few days elapse before death following a complication. A risk-scoring system based on preoperative variables predicts patients in the highest-risk category of failure to rescue with good accuracy. In high-risk patients who develop complications, our results suggest that early intervention, preferably in a high-level intensive care facility with a surgical training program, offers the best chance to reduce failure-to-rescue rates.

Nodal Upstaging During Lung Cancer Resection Is Associated With Surgical Approach.

BACKGROUND Recent reports indicate that thoracoscopic lobectomy for lung cancer may be associated with lower rates of surgical upstaging. We queried a statewide cancer registry for differences in upstaging rates and survival by surgical approach. METHODS The Kentucky Cancer Registry (KCR) collects data, including centralized pathology reporting, on cancer patients treated statewide. We performed a retrospective review from 2010 to 2012 to examine clinical and pathologic stage. We assessed rates of upstaging and whether the surgical approach, thoracotomy (THOR) versus minimally invasive techniques (video-assisted thoracic surgery; VATS), had an impact on final pathologic stage and survival. RESULTS The KCR database from 2010 to 2012 contained information on 2830 lung cancer cases, 1964 having THOR procedure and 500 having VATS resections. Preoperatively, 36.4% of THOR were clinically stage 1a versus 47.4% VATS (p = 0.0002). Of these, final pathologic stage remained stage 1a in 30.5% of THOR procedures and 38.0% of VATS (p = 0.0002). The overall nodal upstaging rate for THOR was 9.9% and 4.8% for VATS (p = 0.002). Decreased nodal upstaging was found with VATS, independent of tumor size and extent of resection (odds ratio 0.6, 95% confidence interval [CI]: 0.387 to 0.985, p = 0.04). However, improved survival was found with VATS compared with THOR (hazard ratio 0.733, 95% CI: 0.592 to 0.907, p = 0.0042). CONCLUSIONS Consistent with other reports, we report a lower upstaging rate with VATS. Nevertheless, there is a survival advantage in VATS patients. Although selection bias may play a role in these observed differences, the improved quality of life measures associated with VATS may explain survival improvement despite lower surgical upstaging.

The relationship between intraoperative blood transfusion and postoperative systemic inflammatory response syndrome.

BACKGROUND Previous observations suggest that intraoperative blood transfusion (IBT) is a risk factor for adverse postoperative outcomes. IBT alters immune function and may predispose to systemic inflammatory response syndrome (SIRS). METHODS Patients in the American College of Surgeons National Surgical Quality Improvement Project database were studied over a 5-year period. Logistic regression identified predictors of SIRS. Propensity matching was used to obtain a balanced set of patients with equivalent preoperative risks for IBT. RESULTS Of 553,288 inpatients, 19,968 (3.6%) developed postoperative SIRS, and 40,378 (7.2%) received IBT. Mortality in patients with SIRS was 13-fold higher than in those without SIRS (13.5% vs 1.0%, P < .001). Multivariate analysis identified the amount of blood transfused during IBT as a significant predictor for development of SIRS (odds ratio, 2.2; P < .0001). After propensity matching, 33,507 matched patients with IBT had significantly increased risk for SIRS compared with non-SIRS matched patients (12.0% vs 6.5%, P < .001). CONCLUSIONS There is a significant association between IBT and the development of SIRS. IBT may induce SIRS, and reductions in IBT may decrease the incidence of postoperative SIRS.

Distinctly perturbed metabolic networks underlie differential tumor tissue damages induced by immune modulator β-glucan in a two-case ex vivo non-small-cell lung cancer study.

Cancer and stromal cell metabolism is important for understanding tumor development, which highly depends on the tumor microenvironment (TME). Cell or animal models cannot recapitulate the human TME. We have developed an ex vivo paired cancerous (CA) and noncancerous (NC) human lung tissue approach to explore cancer and stromal cell metabolism in the native human TME. This approach enabled full control of experimental parameters and acquisition of individual patients target tissue response to therapeutic agents while eliminating interferences from genetic and physiological variations. In this two-case study of non-small-cell lung cancer, we performed stable isotope-resolved metabolomic (SIRM) experiments on paired CA and NC lung tissues treated with a macrophage activator β-glucan and 13C6-glucose, followed by ion chromatography–Fourier transform mass spectrometry (IC-FTMS) and nuclear magnetic resonance (NMR) analyses of 13C-labeling patterns of metabolites. We demonstrated that CA lung tissue slices were metabolically more active than their NC counterparts, which recapitulated the metabolic reprogramming in CA lung tissues observed in vivo. We showed β-glucan-enhanced glycolysis, Krebs cycle, pentose phosphate pathway, antioxidant production, and itaconate buildup in patient UK021 with chronic obstructive pulmonary disease (COPD) and an abundance of tumor-associated macrophages (TAMs) but not in UK049 with no COPD and much less macrophage infiltration. This metabolic response of UK021 tissues was accompanied by reduced mitotic index, increased necrosis, and enhaced inducible nitric oxide synthase (iNOS) expression. We surmise that the reprogrammed networks could reflect β-glucan M1 polarization of human macrophages. This case study presents a unique opportunity for investigating metabolic responses of human macrophages to immune modulators in their native microenvironment on an individual patient basis.

Identifying Esophagectomy Patients at Risk for Predischarge Versus Postdischarge Venous Thromboembolism

BACKGROUND Current guidelines recommend postoperative venous thromboembolism (VTE) chemoprophylaxis for moderate-risk patients (3% rate or greater) and extended-duration chemoprophylaxis for high-risk patients (6% or greater). Large-scale studies of and recommendations for esophagectomy patients are lacking. This study was designed to evaluate the timing, rates, and predictors of postesophagectomy VTE. METHODS Patients undergoing esophagectomies for cancer were identified from the 2005 to 2012 American College of Surgeons National Surgical Quality Improvement database. Timing and rates of VTE (deep venous thrombosis or pulmonary embolism, or both) were calculated. Events were stratified as predischarge or postdischarge. Perioperative factors associated with 30-day rates of predischarge and postdischarge VTE were analyzed. RESULTS Of 3,208 patients analyzed, the surgical approach was Ivor-Lewis (n = 1,131, 35.3%), transhiatal (n = 945, 29.5%), three-field (n = 587, 18.3%), thoracoabdominal (n = 364, 11.3%), and nongastric conduit reconstruction (n = 181, 5.6%). Rates were 2.0% pulmonary embolism, 3.7% deep venous thrombosis, and 5.1% VTE. Overall median length of stay was 11 days (versus 19 days, p < 0.001, if predischarge VTE). Predischarge VTE occurred on median day 9, whereas postdischarge VTE occurred on day 19 (p < 0.001). Only 17% of VTE occurred after discharge. Multivariate analysis identified being male (odds ratio [OR] 2.09, p = 0.018), white race (OR 1.93, p = 0.004), prolonged ventilation (OR 3.24, p < 0.001), and other major complications (OR 1.90, p = 0.005) as independent predictors of predischarge VTE. Older age (OR 1.06 per year, p = 0.006) and major complications (OR 3.14, p = 0.004) were independently associated with postdischarge VTE. CONCLUSIONS Postesophagectomy VTE occurs in a clinically significant proportion of esophageal cancer patients with identifiable risk factors for predischarge and postdischarge events. Elderly patients and patients with major complications are most likely to benefit from extended-duration chemoprophylaxis.

Abstract SY02-02: Exploring the lung cancer metabolome, in vivo and ex vivo, for individualized medicine

2502: Liquid diet introduction of tracers into mice for stable isotope-resolved metabolomics (SIRM) investigations