Carotid stenting and endarterectomy and contralateral carotid occlusion.

BACKGROUND: The presence of contralateral carotid occlusion (CCO) has been controversial throughout the history of carotid intervention. Some studies cite a higher stroke risk in the setting of CCO, whereas other studies document no difference in stroke risk. We investigated the risk of stroke after intervention in the setting of CCO in a large, national, validated dataset. METHODS: Data were obtained from the 2011-2014 American College of Surgeons National Surgical Quality Initiative Project files using targeted carotid endarterectomy (CEA), carotid angioplasty, and carotid artery stenting (CAS) data. Patient and procedural characteristics, and 30-day postoperative outcomes were compared using Pearson χ2 tests for categorical variables and Wilcoxon rank-sum tests for continuous variables. Logistic regression was used for multivariable analysis. The primary outcome measure was the stroke rate, with a secondary outcome of major adverse cardiovascular events. RESULTS: During the study period, 11,948 CEA and 422 CAS procedures were available for study, with significantly fewer CEA (4.73% of all CEA) than CAS (9.95%; P < .0001) occurring in the setting of CCO. CAS was associated with more severe degree of stenosis than CEA (P = .045). Multivariable logistic regression showed that stroke after procedures was higher in patients with CCO than without CCO (odds ratio, 1.73; 95% confidence interval, 1.08-2.76; P = .02), but specific procedure (CEA vs CAS) was not associated with stroke while controlling for confounders. However, when evaluating our secondary composite outcome, CCO was not associated with the outcome while controlling for confounders. CONCLUSIONS: There is currently a bias that CCO confers a higher risk on patients undergoing carotid procedures and this notion is manifest in the proportion of CEA and CAS procedures done in the setting of CCO. Our study observes that CCO provides only a minor influence on periprocedural stroke risk and that other factors are more closely tied to outcomes of CEA and CAS.

Low mortality rates after endovascular aortic repair expand use to high-risk patients.

OBJECTIVE: The 2010 endovascular aneurysm repair (EVAR) trial 2 (EVAR 2) reported that patients with comorbidity profiles rendering them unfit for open aneurysm repair who underwent EVAR did not experience a survival advantage compared with those who did not undergo intervention. These patients experienced a 30-day mortality of 7.3%, whereas reports from similar cohorts reported far lower mortality rates. The primary objective of our study was to compare the incidence of 30-day mortality in low- and high-risk patients undergoing EVAR in a contemporary data set, using patient risk stratification criteria from EVAR 2. Secondarily, we sought to identify risk factors associated with a disproportionate contribution to 30-day mortality risk. METHODS: Data were obtained from the 2005 to 2013 American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) Participant Use Data Files (N = 24,813). Patients were included in the high-risk cohort with the presence of renal, respiratory, or cardiac preoperative criteria alone or in combination. Renal impairment criteria were defined as dialysis and creatinine concentration >2.26 mg/dL. Respiratory impairment criteria included history of chronic obstructive pulmonary disease and preoperative ventilator support. Cardiac impairment criteria included history of myocardial infarction, congestive heart failure, angina, and prior coronary intervention. Patient and procedural characteristics and 30-day postoperative outcomes were compared using Pearson χ2 tests for categorical variables and Wilcoxon rank sum tests for continuous variables. RESULTS: Among 24,813 patients undergoing EVAR, 12,043 (48%) patients were characterized as high risk (at least one impairment criterion); 12,770 (52%) patients were stratified as low risk. The 30-day mortality rate was 1.9% in the high-risk cohort compared with the 7.3% reported by EVAR 2, and it was higher in the high-risk cohort compared with the low-risk cohort (1.9% vs 0.9%; P < .001). Whereas the presence of each comorbidity increased the odds of 30-day mortality (respiratory odds ratio [OR], 1.62; 95% confidence interval [CI], 1.16-2.26; P = .005; cardiac OR, 1.55; 95% CI, 1.14-2.10; P = .005), the presence of renal criteria disproportionately increased the odds of mortality threefold (OR, 3.42; 95% CI, 2.31-5.09; P < .001). CONCLUSIONS: Contemporary 30-day mortality after EVAR in high-risk patients is substantially lower than that reported in the EVAR 2 trial. Whereas low- and high-risk stratification by current comorbidity criteria is appropriate, attention needs to be paid to disproportionate risk contribution from renal disease to mortality compared with cardiac and pulmonary comorbidities. Given the lower mortality risk than previously described, patients stratified as high risk should be thoughtfully considered for definitive EVAR.

The Effect of Clinical Care Location on Clinical Outcomes After Peripheral Vascular Intervention in Medicare Beneficiaries.

OBJECTIVES: Modifications in reimbursement rates by Medicare in 2008 have led to peripheral vascular interventions (PVI) being performed more commonly in outpatient and office-based clinics. The objective of this study was to determine the effects of this shift in clinical care setting on clinical outcomes after PVI. BACKGROUND: Modifications in reimbursement have led to peripheral vascular intervention (PVI) being more commonly performed in outpatient hospital settings and office-based clinics. METHODS: Using a 100% national sample of Medicare beneficiaries from 2010 to 2012, we examined 30-day and 1-year rates of all-cause mortality, major lower extremity amputation, repeat revascularization, and all-cause hospitalization by clinical care location of index PVI. RESULTS: A total of 218,858 Medicare beneficiaries underwent an index PVI between 2010 and 2012. Index PVIs performed in inpatient settings were associated with higher 1-year rates of all-cause mortality (23.6% vs. 10.4% and 11.7%; p < 0.001), major lower extremity amputation (10.1% vs. 3.7% and 3.5%; p < 0.001), and all-cause repeat hospitalization (63.3% vs. 48.5% and 48.0%; p < 0.001), but lower rates of repeat revascularization (25.1% vs. 26.9% vs. 38.6%; p < 0.001) when compared with outpatient hospital settings and office-based clinics, respectively. After adjustment for potential confounders, patients treated in office-based clinics remained more likely than patients in inpatient hospital settings to require repeat revascularization within 1 year across all specialties. There was also a statistically significant interaction effect between location of index revascularization and geographic region on the occurrence of all-cause hospitalization, repeat revascularization, and lower extremity amputation. CONCLUSIONS: Index PVI performed in office-based settings was associated with a higher hazard of repeat revascularization when compared with other settings. Differences in clinical outcomes across treatment settings and geographic regions suggest that inconsistent application of PVI may exist and highlights the need for studies to determine optimal delivery of PVI in clinical practice.

Perioperative Optimization of Geriatric Lower Extremity Bypass in the Era of Increased Performance Accountability.

BACKGROUND: The initiation of bundled payment for care improvement by Centers for Medicare and Medicaid Services (CMS) has led to increased financial and performance accountability. As most vascular surgery patients are elderly and reimbursed via CMS, improving their outcomes will be critical for durable financial stability. As a first step in forming a multidisciplinary pathway for the elderly vascular patients, we sought to identify modifiable perioperative variables in geriatric patients undergoing lower extremity bypass (LEB). METHODS: The 2011-2013 LEB-targeted American College of Surgeons National Surgical Quality Improvement Program database was used for this analysis (n = 5316). Patients were stratified by age <65 (n = 2171), 65-74 (n = 1858), 75-84 (n = 1190), and ≥85 (n = 394) years. Comparisons of patient- and procedure-related characteristics and 30-day postoperative outcomes stratified by age groups were performed with Pearson χ2 tests for categorical variables and Wilcoxon rank-sum tests for continuous variables. RESULTS: During the study period, 5316 total patients were identified. There were 2171 patients aged <65 years, 1858 patients in the 65-74 years age group, 1190 patients in the 75-84 years age group, and 394 patients in the ≥85 years age group. Increasing age was associated with an increased frequency of cardiopulmonary disease (P < 0.001) and a decreased frequency of diabetes, tobacco use, and prior surgical intervention (P < 0.001). Only 79% and 68% of all patients were on antiplatelet and statin therapies, respectively. Critical limb ischemia occurred more frequently in older patients (P < 0.001). Length of hospital stay, transfusion requirements, and discharge to a skilled nursing facility increased with age (P < 0.001). Thirty-day amputation rates did not differ significantly with age (P = 0.12). CONCLUSIONS: Geriatric patients undergoing LEB have unique and potentially modifiable perioperative factors that may improve postoperative outcomes. These modifiers will be the basis of a multidisciplinary care path targeting the geriatric vascular surgery patients.

Laparotomy during endovascular repair of ruptured abdominal aortic aneurysms increases mortality.

OBJECTIVE: Subset analyses from small case series suggest patients requiring laparotomy during endovascular repair of ruptured abdominal aortic aneurysms (REVAR) have worse survival than those undergoing REVAR without laparotomy. Most concomitant laparotomies are performed for abdominal compartment syndrome. This study used data from the American College of Surgeons National Surgical Quality Improvement Program to determine whether the need for laparotomy during REVAR is associated with increased mortality. METHODS: Data were obtained from the 2005 to 2013 National Surgical Quality Improvement Program participant user files based on Current Procedural Terminology (American Medical Association, Chicago, Ill) and International Classification of Diseases-9 Edition coding. Patient and procedure-related characteristics and 30-day postoperative outcomes were compared using Pearson χ2 tests for categoric variables and Wilcoxon rank sum tests for continuous variables. A backward-stepwise multivariable logistic regression model was used to identify patient- and procedure-related factors associated with increased death after REVAR. RESULTS: We identified 1241 patients who underwent REVAR, and 91 (7.3%) required concomitant laparotomy. The 30-day mortality was 60% in the laparotomy group and 21% in the standard REVAR group (P < .001). The major complication rate was also higher in the laparotomy group (88% vs 63%; P < .001). Multivariable analysis showed laparotomy was strongly associated with 30-day mortality (odds ratio, 5.91; 95% confidence interval, 3.62-9.62; P < .001). CONCLUSIONS: Laparotomy during REVAR is a commonly used technique for the management of elevated intra-abdominal pressure and abdominal compartment syndrome development. The results of this study strongly confirm findings from smaller studies that the need for laparotomy during REVAR is associated with significantly worse 30-day survival.

Significant variation in P2Y12 inhibitor use after peripheral vascular intervention in Medicare beneficiaries.

UNLABELLED: There is no consensus regarding whether to use antithrombotic medications in patients with peripheral artery disease after lower-extremity peripheral vascular intervention. OBJECTIVES: The main hypothesis is that significant variation exists regarding use of antithrombotic medications after lower-extremity peripheral vascular intervention. We sought to examine the patterns of postprocedural antithrombotic medication use and associated factors in Medicare patients. METHODS: We measured rates of P2Y12 inhibitor use after peripheral vascular intervention in a 100% national sample of Medicare beneficiaries with Part D prescription drug coverage. We used logistic regression modeling to examine associations between patient and clinical factors and P2Y12 inhibitor use. RESULTS: Between 2010 and 2012, a total of 85,830 patients underwent peripheral vascular intervention and had prescription drug claims. Overall, 18.3% of patients were treated with an oral anticoagulant, 19.1% received no P2Y12 inhibitor, 30.8% received a P2Y12 inhibitor before and after the procedure, 6.2% received a P2Y12 inhibitor for up to 30 days after the procedure, and 25.6% received a P2Y12 inhibitor for more than 30 days after the procedure. After adjustment, factors associated with P2Y12 inhibitor use included male sex; black race; history of renal disease, dementia, or heart failure; physician specialty; and clinical setting of the procedure. We observed a strong interaction effect between clinical setting and physician specialty (P < .001). CONCLUSIONS: One-fifth of patients who underwent lower-extremity peripheral vascular intervention did not fill a prescription for a P2Y12 inhibitor. Patients whose operators were surgeons or radiologists had lower odds of P2Y12 inhibitor use. More research to determine the optimal use and duration of antithrombotic medications after the procedure is warranted.

Impact of patient selection and treatment strategies on outcomes after lobectomy for biopsy-proven stage IIIA pN2 non-small cell lung cancer.

OBJECTIVES: We evaluated the impact of patient selection and treatment strategies on long-term outcomes of patients who had lobectomy after induction therapy for stage IIIA pN2 non-small cell lung cancer (NSCLC). METHODS: The impact of various patient selection, induction therapy and operative strategies on survival of patients with biopsy-proven stage IIIA pN2 NSCLC who received induction chemotherapy ± radiation followed by lobectomy from 1995 to 2012 was assessed using Cox proportional hazards analysis. RESULTS: From 1995 to 2012, 111 patients had lobectomy for stage IIIA pN2 NSCLC after chemotherapy ± radiation with an overall 5-year survival of 39%. The use of induction chemoradiation decreased over time; from 1996 to 2007, 46/65 (71%) patients underwent induction chemoradiation, whereas from 2007 to 2012, 36/46 (78%) patients underwent induction chemotherapy. The use of video-assisted thoracoscopic surgery (VATS) increased over the time period of the study, from 0/26 (0%) in 1996-2001, to 4/39 (10%) in 2002-07 to 33/46 (72%) in 2008-12. Compared with patients given induction chemotherapy alone, patients given additional induction radiation were more likely to have complete pathologic response (30 vs 11%, P = 0.01) but had worse 5-year survival in univariable analysis (31 vs 48%, log-rank P = 0.021). Patients who underwent pathologic mediastinal restaging following induction therapy but prior to resection had an improved overall survival compared with patients who did not undergo pathologic mediastinal restaging {5-year survival: 45.2 [95% confidence interval (CI): 33.9-55.9] vs 13.9% (95% CI: 2.5-34.7); log-rank, P = 0.004}. In multivariable analysis, the particular induction therapy strategy and the surgical approach used, as well as the extent of mediastinal disease were not important predictors of survival. However, pathologic mediastinal restaging was associated with improved survival (HR 0.39; 95% CI: 0.21-0.72; P = 0.003). CONCLUSIONS: For patients with stage IIIA pN2 NSCLC, the VATS approach or the addition of radiation to induction therapy can be selectively employed without compromising survival. The strategy of assessing response to induction therapy with pathologic mediastinal restaging allows one to select appropriate patients for complete resection and is associated with a 5-year overall survival of 39% in this population.

Contemporary review of minimally invasive pancreaticoduodenectomy.

AIM: To assess the current literature describing various minimally invasive techniques for and to review short-term outcomes after minimally invasive pancreaticoduodenectomy (PD). METHODS: PD remains the only potentially curative treatment for periampullary malignancies, including, most commonly, pancreatic adenocarcinoma. Minimally invasive approaches to this complex operation have begun to be increasingly reported in the literature and are purported by some to reduce the historically high morbidity of PD associated with the open technique. In this systematic review, we have searched the literature for high-quality publications describing minimally invasive techniques for PD-including laparoscopic, robotic, and laparoscopic-assisted robotic approaches (hybrid approach). We have identified publications with the largest operative experiences from well-known centers of excellence for this complex procedure. We report primarily short term operative and perioperative results and some short term oncologic endpoints. RESULTS: Minimally invasive techniques include laparoscopic, robotic and hybrid approaches and each of these techniques has strong advocates. Consistently, across all minimally invasive modalities, these techniques are associated less intraoperative blood loss than traditional open PD (OPD), but in exchange for longer operating times. These techniques are relatively equivalent in terms of perioperative morbidity and short term oncologic outcomes. Importantly, pancreatic fistula rate appears to be comparable in most minimally invasive series compared to open technique. Impact of minimally invasive technique on length of stay is mixed compared to some traditional open series. A few series have suggested that initiation of and time to adjuvant therapy may be improved with minimally invasive techniques, however this assertion remains controversial. In terms of short-terms costs, minimally invasive PD is significantly higher than that of OPD. CONCLUSION: Minimally invasive approaches to PD show great promise as a strategy to improve short-term outcomes in patients undergoing PD, but the best results remain isolated to high-volume centers of excellence.

Targeting N-cadherin increases vascular permeability and differentially activates AKT in melanoma.

OBJECTIVE: We investigate the mechanism through which N-cadherin disruption alters the effectiveness of regional chemotherapy for locally advanced melanoma. BACKGROUND: N-cadherin antagonism during regional chemotherapy has demonstrated variable treatment effects. METHODS: Isolated limb infusion (ILI) with melphalan (LPAM) or temozolomide (TMZ) was performed on rats bearing melanoma xenografts after systemic administration of the N-cadherin antagonist, ADH-1, or saline. Permeability studies were performed using Evans blue dye as the infusate, and interstitial fluid pressure was measured. Immunohistochemistry of LPAM-DNA adducts and damage was performed as surrogates for LPAM and TMZ delivery. Tumor signaling was studied by Western blotting and reverse-phase protein array analysis. RESULTS: Systemic ADH-1 was associated with increased growth and activation of the PI3K (phosphatidylinositol-3 kinase)-AKT pathway in A375 but not DM443 xenografts. ADH-1 in combination with LPAM ILI improved antitumor responses compared with LPAM alone in both cell lines. Combination of ADH-1 with TMZ ILI did not improve tumor response in A375 tumors. ADH-1 increased vascular permeability without effecting tumor interstitial fluid pressure, leading to increased delivery of LPAM but not TMZ. CONCLUSIONS: ADH-1 improved responses to regional LPAM but had variable effects on tumors regionally treated with TMZ. N-cadherin-targeting agents may lead to differential effects on the AKT signaling axis that can augment growth of some tumors. The vascular targeting actions of N-cadherin antagonism may not augment some regionally delivered alkylating agents, leading to a net increase in tumor size with this type of combination treatment strategy.

Emerging role of contrast-enhanced MRI in diagnosing vascular malformations.

Vascular malformations comprise a diverse and rare group of lesions which generally pose a formidable treatment challenge. Requisite for optimal surgical planning are imaging modalities capable of delineating involved anatomy and malformation flow characteristics. In this regard, we and others have purported the advantages of contrast-enhanced MRI. Here, we review the current body of literature regarding the emerging of role of contrast enhanced MRI for the management of vascular malformations.

Trials of nonoperative management exceeding 3 days are associated with increased morbidity in patients undergoing surgery for uncomplicated adhesive small bowel obstruction.

BACKGROUND: Controversy exists over how long trials of nonoperative management should be pursued in patients with uncomplicated adhesive small bowel obstructions (ASBOs) before deciding to proceed with surgery. The purpose of this study was to determine the effect of incremental delays in surgery on the 30-day postoperative outcomes of patients undergoing surgery for uncomplicated ASBO. METHODS: American College of Surgeons National Surgical Quality Improvement Program 2005-2011 data were used to identify patients with uncomplicated ASBO in whom a trial of nonoperative management was attempted. Multivariate logistic or linear regression model was created to determine the independent association between the length of preoperative hospitalization and 30-day postoperative outcomes after adjustment for patient- and procedure-related factors. RESULTS: A total of 9,297 patients were included in the study. The 30-day postoperative mortality and overall morbidity rates of the entire cohort were 4.4% and 29.6%, respectively. The median postoperative length of hospitalization was 7 days (interquartile range, 5-11 days). After risk adjustment, there was no association between preoperative length of hospitalization and 30-day postoperative mortality. In contrast, increased 30-day overall morbidity was observed in patients who received their operation after a preoperative length of hospitalization of 3 days compared with earlier in their hospitalization. Furthermore, an increased postoperative length of hospitalization was found in patients who were operated on after a preoperative length of hospitalization of 4 days. CONCLUSION: Trials of nonoperative management for uncomplicated ASBO exceeding 3 days are associated with increased morbidity and postoperative length of hospitalization. These trials should therefore generally not extend beyond this time point. LEVEL OF EVIDENCE: Therapeutic study, level IV.

Atypical aortic thrombus: should nonoperative management be first line?

BACKGROUND: Aortic thrombus in the absence of atherosclerotic plaque or aneurysm is rare, and its optimal management remains unclear. Although atypical aortic thrombus (AAT) has been historically managed operatively, successful nonoperative strategies have been recently reported. Here, we report our experience in treating patients with AAT that has evolved from a primarily operative approach to a first-line, nonoperative strategy. METHODS: Records of patients treated for AAT between 2008 and 2011 at our institution were reviewed. RESULTS: Ten female and three male patients with ages ranging from 27 to 69 were identified. Seven were treated operatively and 6 nonoperatively. Initial presentation was variable and included limb thromboembolic events (n = 6), visceral ischemia (n = 5), and stroke (n = 1). Associated risk factors included hypercoagulability (76%; n = 10) and hyperlipidemia (38%, n = 5). In the nonoperative group, complete thrombus resolution was obtained via anticoagulation (n = 5) or systemic thrombolysis (n = 1). Complete thrombus extraction was achieved in all operative patients. There were 11 significant complications in 5 of the 7 patients (71%) in the operative group, including intraoperative lower extremity embolism, pericardial effusion, stroke, and 1 death. There was 1 complication in the patients treated nonoperatively. The median hospital length of stay was 9 days (range 3-49) for those treated nonoperatively and 30 days (range 4-115) for those undergoing operative thrombectomy. CONCLUSIONS: Although AAT has traditionally been treated operatively, nonoperative management of AAT with anticoagulation or thrombolysis is feasible in selected patients and may lessen morbidity and length of hospitalization in those patients for whom it is appropriate.

Hepatic resection for hepatocellular carcinoma: do contemporary morbidity and mortality rates demand a transition to ablation as first-line treatment?

BACKGROUND: Despite the rising incidence of hepatocellular carcinoma (HCC), challenges and controversy persist in optimizing treatment. As recent randomized trials suggest that ablation can have oncologic equivalence compared with resection for early HCC, the relative morbidity of the 2 approaches is a central issue in treatment decisions. Although excellent contemporary perioperative outcomes have been reported by a few hepatobiliary units, it is not clear that they can be replicated in broader practice. Our objective was to help inform this treatment dilemma by defining perioperative outcomes in a broader set of patients as represented in NSQIP-participating institutions. STUDY DESIGN: Mortality and morbidity data were extracted from the 2005-2010 NSQIP Participant Use Data Files based on Current Procedural Terminology (hepatectomy and ablation) and ICD-9 (HCC). Perioperative outcomes were reviewed, and factors associated with morbidity and mortality were identified with multivariable logistic regression. RESULTS: Eight hundred and thirty-seven (52%) underwent minor hepatectomy, 444 (28%) underwent major hepatectomy, and 323 (20%) underwent surgical ablation. Mortality rates were 3.4% for minor hepatectomy, 3.7% for ablation, and 8.3% for major hepatectomy (p < 0.01). Major complication rates were 21.3% for minor hepatectomy, 9.3% for ablation, and 35.1% for major hepatectomy (p < 0.01). When controlling for confounders, ablation was associated with decreased mortality (adjusted odds ratio = 0.20; 95% CI, 0.04-0.97; p = 0.046) and major complications (adjusted odds ratio = 0.34; 95% CI, 0.22-0.52; p < 0.001). CONCLUSIONS: Exceedingly high complication rates after major hepatectomy for HCC exist in the broader NSQIP treatment environment. These data strongly support the use of parenchymal-sparing minor resections or ablation over major hepatectomy for early HCC when feasible.

Ureteral stenting in laparoscopic colorectal surgery.

BACKGROUND: Few studies have examined the current status of ureteral stent use or the indications for stenting, particularly in laparoscopic colorectal surgery. This study examines current national trends and predictors of ureteral stenting in patients undergoing major colorectal operations and the subsequent effects on perioperative outcomes. METHODS: The 2005-2011 National Surgical Quality Improvement participant user files were used to identify patients undergoing laparoscopic segmental colectomy, low anterior resection, or proctectomy. Trends in stent use were assessed across procedure types. To estimate the predictors of stent utilization, a forward-stepwise logistic regression model was used. A 3:1 nearest neighbor propensity match with subsequent multivariable adjustment was then used to estimate the impact of stents. RESULTS: A total of 42,311 cases were identified, of which 1795 (4.2%) underwent ureteral stent placement. Predictors of stent utilization included diverticular disease, need for radical resection (versus segmental colectomy), recent radiotherapy, and more recent calendar year. After adjustment, ureteral stenting appeared to be associated with a small increase in median operative time (44 min) and a trivial increase in length of stay (5.4%, P<0.001). However, there were no significant differences in morbidity or mortality. CONCLUSIONS: We describe the clinical predictors of ureteral stent usage in this patient population and report that while stenting adds to operative time, it is not associated with significantly increased morbidity or mortality after adjusting for diagnosis and comorbidities. Focused institutional studies are necessary in the future to address the utility of ureteral stents in the identification and possible prevention of iatrogenic injury.

Does the presence of coronary artery disease impact perioperative outcomes following partial hepatectomy?

INTRODUCTION: Coronary artery disease (CAD) is often considered a contraindication to hepatectomy despite a lack of data to support this practice. The purpose of this study is to evaluate the impact of CAD on postoperative outcomes in patients undergoing hepatectomy. MATERIAL AND METHODS: A total of 1,206 consecutive patients undergoing hepatectomy from August 1995 to June 2009 were included. Propensity matching was performed to identify differences in morbidity and mortality between patients with and without CAD. Subgroup analyses were performed to stratify patients based on the severity of CAD and the interval between coronary intervention and hepatectomy. RESULTS: Of all patients, 138 (11.4%) had a diagnosis of CAD and were more likely to have a malignant diagnosis and other comorbid conditions including renal insufficiency, COPD, and diabetes. Matched patients with CAD had no significant differences in complication rates, with 2.2 and 5.8% of CAD patients experiencing a postoperative myocardial infarction or arrhythmia, respectively. Propensity matching failed to identify differences in mortality or morbidity. Subgroup analysis revealed similar rates of mortality and complications regardless of the severity of CAD or the time interval between coronary intervention and hepatectomy. CONCLUSION: Despite the increased prevalence of major medical comorbidities, selected patients with CAD can safely undergo hepatectomy with acceptable rates of postoperative morbidity and mortality.

Age and gender differences in substance screening may underestimate injury severity: a study of 9793 patients at level 1 trauma center from 2006 to 2010.

BACKGROUND: Although the relationship between psychoactive substance use and injury is known, evidence remains conflicting on the impact of substance use on clinical outcomes after injury. We hypothesized that preinjury substance use would negatively impact clinical outcomes. METHODS: National Trauma Registry American College of Surgeons identified patients (n = 9793) presenting to Duke Hospital from 2006 to 2010. Logistic regression models assessed potential predictors of receiving substance screening, mortality, length of stay, ventilator requirement, intensive care admission, or emergency department disposition. RESULTS: Forty-seven percent (4607/9793) of patients received blood alcohol screen (BAS) and 31% (3017/9793) received urine drug screen (UDS). Men were more likely to receive both BASs (P < 0.001) and UDSs (P = 0.001) than women after controlling for potential confounders. There was no significant difference between men and women over the legal limit for alcohol (OLLA; 27.2%, 95% confidence interval [CI]: 25.7%-28.8% versus 24.8%, 95% CI: 22.3%-27.5%). Similarly, younger patients more likely received both BASs (P < 0.001) and UDSs (P < 0.001) compared with older patients. The proportion of patients aged ≤45 y OLLA (26.5 %, 95% CI: 24.9%-28.2%) was similar to those aged >45 y OLLA (26.8%, 95% CI: 24.5%-29.3%). After controlling for potential confounders neither alcohol, nor tetrahydrocannabinol, nor cocaine was predictive of mortality, ventilator requirement, length of stay, or emergency department disposition, but a higher alcohol level (P = 0.0174) predicted intensive care admission. CONCLUSIONS: Females and those aged >45 y are less likely to receive BASs and UDSs. Differential screening that is biased may place patients at risk for receiving inadequate care.

Pelvic exenteration for the treatment of locally advanced colorectal and bladder malignancies in the modern era.

BACKGROUND: Although pelvic exenteration (PE) remains an important treatment for advanced pelvic malignancies, it has historically been associated with high morbidity and mortality with unclear long-term benefits. The objectives of this study were (1) estimate complication and mortality rates, (2) determine predictors of complications, and (3) estimate overall survival after PE for patients with locally advanced colorectal and bladder tumors. METHODS: A total of 377 patients were retrospectively identified from the 2005-2010 NSQIP PUF and an additional 1,111 from the 2004-2010 Surveillance Epidemiology and End Results database with T4M0 colorectal or bladder cancers. A logistic regression model was fitted to estimate early morbidity and mortality. The Kaplan-Meier method was used to estimate survival after PE compared to nonoperative management. RESULTS: Fifty-seven percent of patients had a complication, but 30-day mortality was only 2%. Patients with preoperative dyspnea and higher ASA class had the highest risk of morbidity. PE for the treatment of T4M0 rectal and bladder cancer was associated with significantly improved long-term survival compared to nonoperative therapy. CONCLUSIONS: PE is associated with a high complication rate but low 30-day mortality. The results of this study provide strong evidence to support PE as a viable treatment option for locally advanced rectal and bladder malignancies in appropriately selected patients.

SRC family kinase inhibition as a novel strategy to augment melphalan-based regional chemotherapy of advanced extremity melanoma.

BACKGROUND: Src kinase inhibition has been shown to augment the efficacy of chemotherapy. Dasatinib, a dual Src/Abl kinase inhibitor approved for the treatment of CML, is under investigation as monotherapy for tumors with abnormal Src signaling, such as melanoma. The goal of this study was to determine if Src kinase inhibition using dasatinib could enhance the efficacy of regionally administered melphalan in advanced extremity melanoma. METHODS: The mutational status of c-kit and patterns of gene expression predictive of dysregulated Src kinase signaling were evaluated in a panel of 26 human melanoma cell lines. The effectiveness of dasatinib was measured by quantifying protein expression and activation of Src kinase, focal adhesion kinase, and Crk-associated substrate (p130(CAS)), in conjunction with in vitro cell viability assays using seven melanoma cell lines. Utilizing a rat model of regional chemotherapy, we evaluated the effectiveness of systemic dasatinib in conjunction with regional melphalan against the human melanoma cell line, DM443, grown as a xenograft. RESULTS: Only the WM3211 cell line harbored a c-kit mutation. Significant correlation was observed between Src-predicted dysregulation by gene expression and sensitivity to dasatinib in vitro. Tumor doubling time for DM443 xenografts treated with systemic dasatinib in combination with regional melphalan (44.8 days) was significantly longer (p = 0.007) than either dasatinib (21.3 days) or melphalan alone (24.7 days). CONCLUSIONS: Systemic dasatinib prior to melphalan-based regional chemotherapy markedly improves the efficacy of this alkylating agent in this melanoma xenograft model. Validation of this concept should be considered in the context of a regional therapy clinical trial.

Predicting disease progression after regional therapy for in-transit melanoma.

IMPORTANCE: Although approximately 30% to 50% of patients experience a complete response after regional chemotherapy for in-transit melanoma, a subset of patients will develop rapidly progressive disease. In the current era of an expanding armamentarium, including both regional and systemic options for treating advanced melanoma, identifying perioperative factors that predict disease progression may obviate unnecessary morbidity associated with regional therapy and avoid delays in systemic therapy. OBJECTIVE: To identify patient-related clinical and pathological variables, as well as procedural factors, that correlate with disease progression. DESIGN: Using a prospectively maintained database, we identified patients who either underwent first-time melphalan-based isolated limb infusion (ILI) or first-time hyperthermic isolated limb perfusion (HILP) for in-transit melanoma. Response was defined using modified Response Evaluation Criteria in Solid Tumors for cutaneous disease at 3 months after treatment. Survival analyses were performed using the Kaplan-Meier method, with the differences in survival curves compared using a log-rank test. Potential preoperative and procedural predictors of in-field progressive disease were analyzed using logistic regression. PARTICIPANTS: Of the 258 patients included in the database, 215 were identified as having undergone first-time regional therapy. Of these 215 patients, 134 underwent ILI, and 81 underwent HILP. EXPOSURE: Regional therapy (ILI or HILP). MAIN OUTCOMES AND MEASURES: Complete response or progressive disease. RESULTS: Of 134 patients who underwent ILI, 43 (32.1%) experienced in-field progressive disease. Of 81 patients who underwent HILP, 9 (11.1%) experienced in-field progressive disease. The median survival for patients with in-field progressive disease was 20.3 months for the ILI cohort and 15.0 months for the HILP cohort. In general, patients with progressive disease were younger, with advanced-stage melanoma and increased tumor burden. Compared with patients who experienced a complete response, patients with in-field progressive disease after ILI were younger (odds ratio, 1.06 [95% CI, 0.90-0.98]; P = .002). For patients who underwent HILP, no clinically relevant preoperative predictors of in-field progressive disease were identified. Procedural variables, including chemotherapeutic dosing, degree of acidosis or base deficit achieved, and peak temperature attained, were not predictors of in-field progressive disease after ILI or HILP. CONCLUSIONS AND RELEVANCE: Patient, clinical, and procedural factors are unreliable predictors of in-field progressive disease after regional therapy in patients with in-transit melanoma. Defining the potential utility of molecular markers in predicting response or failure of regional therapy should be the focus of future research efforts.

Examining reoperation and readmission after hepatic surgery.

BACKGROUND: Although the perioperative mortality from hepatic resection has improved considerably, this procedure is still associated with substantial morbidity and resource use. The goal of this investigation was to characterize the incidence, patterns, and risk factors for early reoperation and readmission after hepatectomy. STUDY DESIGN: Perioperative outcomes of 1,281 patients undergoing hepatic resection at an academic center from 1996 to 2009 were analyzed. The indications for early reoperation and readmission (90 days) were reviewed. Multivariate logistic regression analysis was performed to determine variables associated with reoperation and readmission. A scoring system was generated to predict the need for readmission after hepatectomy. RESULTS: Eighty-seven patients (6.8%) required reoperation. The perioperative mortality in patients requiring reoperation was significantly higher than for those not requiring reoperation (23.0% vs 3.4%; p < 0.001). Variables associated with reoperation included male sex, performance of concomitant major nonhepatic procedures, and greater intraoperative blood loss. One hundred and eighty-four patients (14.4%) required readmission. Variables associated with readmission included major hepatectomy, development of major postoperative complications, and index hospitalization >7 days. A Readmission Prediction Score ranging from 0 to 4 was generated and directly correlated with need for readmission. CONCLUSIONS: In the current era of hepatic surgery, early reoperation and readmission remain relatively frequent. As we care for patients who are increasingly receiving regionalized care far from home, we must be mindful of patients at increased risk for readmission. The development of strategies to minimize the complications that necessitate reoperation and readmission is critical to improving patient care.