Neoadjuvant therapy for localized pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive tumor with poor prognosis and rising incidence globally. Multimodal therapy that includes surgical resection and chemotherapy with or without radiation offers the best chance for optimal outcomes. The development of established criteria for anatomic staging of local primary tumors into potentially resectable (PR), borderline resectable (BR), and locally advanced (LA) has greatly clarified the optimal treatment strategies. While upfront surgical resection was traditionally the recommended approach for localized PDAC, increasingly neoadjuvant therapy (NT) is recommended prior to surgery. Whereas NT can lead to downstaging that facilitates surgical resection for BR/LA cancers, NT also enhances patient selection for surgery, improves margin-negative resection rates, and increases the odds of completing multimodality therapy for all patients with PDAC. Herein, we review the rationale for NT for localized PDAC and summarize existing and ongoing literature.

Quality of Life and Real-time Patient Experience During Neoadjuvant Therapy: A Prospective Cohort Study.

OBJECTIVE: To use a customized smartphone application to prospectively measure QOL and the real-time patient experience during neoadjuvant therapy (NT). BACKGROUND: NT is increasingly used for patients with localized gastrointestinal (GI) cancers. There is little data assessing patient experience and quality of life (QOL) during NT for GI cancers. METHODS: Patients with GI cancers receiving NT were instructed on using a customized smartphone application through which the Functional Assessment of Cancer Therapy-General (FACT-G) questionnaire, a validated measure of health-related QOL, was administered at baseline, every 30 days, and at the completion of NT. Participants also tracked their moods and symptoms and used free-text journaling functionalities in the application. Mean overall and subsection health-related QOL scores were calculated during NT. RESULTS: Among 104 enrolled patients, the mean age was 60.5 ± 11.5 years and 55% were males. Common cancer diagnoses were colorectal (40%), pancreatic (37%), and esophageal (15%). Mean overall FACT-G scores did not change during NT ( P = 0.987). While functional well-being scores were consistently the lowest and social well-being scores the highest, FACT subscores similarly did not change during NT (all P > 0.01). The most common symptoms reported during NT were fatigue, insomnia, and anxiety (39.3%, 34.5%, and 28.3% of patient entries, respectively). Qualitative analysis of free-text journaling entries identified anxiety, fear, and frustration as the most common themes, but also the importance of social support systems and confidence in health care providers. CONCLUSIONS: While patient symptom burden remains high, results of this prospective cohort study suggest QOL is maintained during NT for localized GI cancers.

Combined radiotherapy and immune checkpoint inhibition for the treatment of advanced hepatocellular carcinoma.

Hepatocellular Carcinoma (HCC) is one of the most common cancers and a leading cause of cancer related death worldwide. Until recently, systemic therapy for advanced HCC, defined as Barcelona Clinic Liver Cancer (BCLC) stage B or C, was limited and ineffective in terms of long-term survival. However, over the past decade, immune check point inhibitors (ICI) combinations have emerged as a potential therapeutic option for patients with nonresectable disease. ICI modulate the tumor microenvironment to prevent progression of the tumor. Radiotherapy is a crucial tool in treating unresectable HCC and may enhance the efficacy of ICI by manipulating the tumor microenvironment and decreasing tumor resistance to certain therapies. We herein review developments in the field of ICI combined with radiotherapy for the treatment of HCC, as well as look at challenges associated with these treatment modalities, and review future directions of combination therapy.

Updates and Expert Opinions on Liver Transplantation for Gastrointestinal Malignancies.

Transplant oncology is a relatively new field in which transplantation is used to treat patients who would otherwise be unresectable. New anticancer treatment paradigms using tumor and transplant immunology and cancer immunogenomics are emerging. In turn, liver transplantation (LT) has become a potential therapy for certain patients with colorectal cancer (CRC) with liver metastasis, hepatocellular (HCC), cholangiocarcinoma (CCA), and metastatic neuroendocrine tumor (NET) of the liver. Although there are established criteria for LT in HCC, evidence regarding LT as a treatment modality for certain gastrointestinal malignancies is still debated. The aim of this review is to highlight updates in the role of LT for certain malignancies, including HCC, metastatic CRC, hilar CCA, and neuroendocrine tumor (NET), as well as contextualize LT use and discuss controversies in transplant oncology.

The Role of Targeted Therapy in the Multi-Disciplinary Approach to Colorectal Liver Metastasis.

Colorectal cancer (CRC) is the second most common cause of cancer-related mortality in the United States. Among newly diagnosed patients with CRC, 20% will present with metastatic disease and another 25% will develop metastases. The surgical resection of the primary tumor and metastatic disease sites confers the best chance at long-term survival. Unfortunately, many patients will recur after resection or present with unresectable disease. As such, metastatic CRC is commonly treated with a combination of surgery, systemic therapy, and/or liver-directed therapies. Despite best efforts, 5-year survival for unresectable metastatic CRC is only about 20%. CRC is a heterogeneous disease and the underlying genetic differences inform behavior, treatment strategy, and prognosis. Given the limitations of cytotoxic chemotherapy and the growing role of molecular profiling, research has focused on identifying and developing targeted therapies. We herein review how genetic profiling informs prognosis, crucial cell-signaling pathways that play a role in CRC carcinogenesis, and currently approved targeted therapies for metastatic CRC.

Expert Insights on Current Treatments for Hepatocellular Carcinoma: Clinical and Molecular Approaches and Bottlenecks to Progress.

Hepatocellular carcinoma (HCC) is a primary liver tumor that typically occurs in the setting of chronic liver disease/cirrhosis. Treatment modalities for HCC have evolved and given the variety of treatment options, a multi-disciplinary approach requiring input from surgical, medical, and radiation oncology, hepatology, and interventional radiology is necessary. Multiple advances have been made over the last decade regarding treatment of HCC, especially advanced disease. Resection and transplantation remain as cornerstone curative-intent treatment options. For patients who are not candidates for curative-intent therapy, exciting progress has been made in molecular and cellular approaches to systemic therapy for HCC including immunotherapies and tyrosine kinase inhibitors. Although the prognosis for advanced HCC remains poor, the armamentarium of therapies has increased, and valuable years of life can be gained with these therapies. While the main therapeutic modality for early-stage disease remains resection, multimodal immunotherapy has emerged as first-line treatment for advanced disease. We herein review different clinical and molecular treatment modalities related to the treatment of HCC, as well as provide insights into future directions for HCC treatment. We highlight how research and progress are needed to move into a new era of molecular and cellular treatments.

Advances in Targeted Immunotherapy for Hepatobiliary Cancers.

Cancer of the hepatobiliary system can be divided into primary liver cancer and biliary tract cancer (BTC), which includes hepatocellular carcinoma (HCC), cholangiocarcinoma (CCA), and gallbladder cancer (GBC). These aggressive cancers often present at an advanced stage or among patients with poorly preserved liver function. The primary treatment for HCC and BTC when diagnosed early is surgical resection, but given the high rate of recurrence and often advanced stage at diagnosis, many patients will require systemic therapy. Unfortunately, even with systemic therapy, long-term survival is poor. The immune system plays an important role in preventing cancer progression. The unique immune environment of the liver and subsequent alterations to the immune microenvironment by tumor cells to create a favorable microenvironment plays a key role in the progression of HCC and BTC. Due to the paucity of effective systemic therapies and distinctive immune environment of the liver, research and clinical trials are investigating the use of immunotherapy in HCC and BTC. This review will focus on current immunotherapies and emerging data for the treatment of HCC and BTC.

Highlighting novel targets in immunotherapy for liver cancer.

INTRODUCTION: Alterations to the hepatic immune microenvironment can play a key role in the development and progression of cancer. This is especially true in the liver due to its evolutionarily conserved immunotolerant state. The presence of chronic inflammation can facilitate the development and progression of hepatocellular carcinoma (HCC) by disrupting the hepatic immune microenvironment. Recently, the addition of the immunotherapy atezolizumab (PD-L1 inhibitor) with bevacizumab (VEGF inhibitor) became the recommended first-line systemic treatment for advanced HCC. AREAS COVERED: Given recent updates to the guidelines and emerging data on immunotherapy, we herein provide an overview of currently available and novel immunotherapy approaches for the treatment of HCC, including immune checkpoint inhibitors, adoptive cell therapy, and vaccine development. This review performed an extensive literature search to investigate benchwork, clinical research, and clinical trials that evaluate current immunotherapy and establish new targets. Literature was focused on the most up-to-date research and included ongoing clinical trials to better evaluate the obstacles and future direction of the field. EXPERT OPINION: Given the heterogeneity of HCC tumors, improvement in outcomes will likely come from targeting multiple immune mechanisms. Continued research and clinical trials of combination immunotherapies are necessary to move the field forward.

Impact of the Timing of Foot Tissue Resection on Outcomes in Patients Undergoing Revascularization for Chronic Limb-Threatening Ischemia.

The objective of this study is to describe utilization of revascularization and tissue resection in patients with chronic limb-threatening ischemia (CLTI) and determine whether the timing of resection impacts outcomes. Revascularizations for CLTI were queried (ACS-NSQIP 2011-2015). Outcomes included 30-day major adverse limb events (MALE), major adverse cardiac events (MACE), length of stay (LOS), operative time, 30-day readmissions, and wound infections. Groups included revascularization alone, revascularization/tissue resection during the same procedure (concurrent), or revascularization/delayed tissue resection (delayed). Resections were debridement or transmetatarsal amputations. Multivariate logistic regression determined risk-adjusted effects of tissue resection on outcomes. There was no difference in overall 30-day MACE or MALE between groups (P = .70 and P = .35, respectively). Length of stay (6.1 days revascularization alone vs 7.8 days concurrent vs 8.7 days delayed, P < .0001) was longer in patients who underwent any tissue resection. Highest 30-day readmission and operative time was the concurrent group (P = .02 and P < .0001, respectively). Wound infection was highest in the delayed group (1.4% revascularization alone vs 1.3% concurrent vs 6.2% delayed, P < .0001). After risk adjustment, timing of resection did not impact LOS for concurrent and delayed groups compared to revascularization alone (both P < .0001). Debridement and minor amputations can be done concurrently in patients undergoing revascularization for CLTI.

Sex-Based Differences Among Experimental Swine Abdominal Aortic aneurysms.

BACKGROUND: Female sex protects against abdominal aortic aneurysms (AAAs); however, the mechanisms behind these sex-based differences remain unknown. The purpose of this study was to explore the role of sex and sex hormones in AAA formation among swine. MATERIALS AND METHODS: Using a previous validated model, infrarenal AAA were surgically created in uncastrated male (n = 8), female (n = 5), and castrated male (n = 4) swine. Aortic dilation was measured on postoperative day 28 during the terminal procedure and compared to initial aortic diameter measured during the index procedure. Tissue was analyzed for immunohistochemistry, cytokine array, gelatin zymography, serum 17ß-estradiol, and testosterone assay. RESULTS: Uncastrated males had significantly larger maximal aortic dilation compared to castrated males (113.5% ± 11.4% versus 38.1% ± 4.5%, P = 0.0012). Females had significantly higher mean aortic dilation compared to castrated males (96.2% ± 7.5% versus 38.1% ± 4.5%, P = 0.0004). Aortic diameters between females and uncastrated males were not significantly different on day 28. Female swine had significantly higher concentrations of 17ß-estradiol compared with uncastrated males (1590 ± 873.3 ng/mL versus 95.2 ± 2.3 ng/mL, P = 0.047), with no significant difference between females and castrated males. Uncastrated male AAA demonstrated significantly more elastin degradation compared with female and castrated males (P = 0.01 and <0 .01, respectively). No differences existed for T-cells or smooth muscle cells between groups. Multiple proinflammatory cytokines were elevated within uncastrated male aortic walls compared to females and castrated males. CONCLUSIONS: Sex hormones, specifically 17ß-estradiol and testosterone, influence experimental swine AAA formation as demonstrated by increased aneurysm size, collagen turnover, and elastolysis in uncastrated males in processes reflective of human disease.

Pharmacologic inhibition of transient receptor channel vanilloid 4 attenuates abdominal aortic aneurysm formation.

Abdominal aortic aneurysm (AAA) formation is characterized by inflammation, leukocyte infiltration, and vascular remodeling. This study investigates the role of TRPV4 channels, which are transmembrane calcium channels that can regulate vascular tone, in modulating AAA formation. The elastase-treatment model of AAA in C57BL6 (WT) mice and Angiotensin II treatment model in ApoE-/- mice were used to confirm our hypotheses. The administration of a specific TRPV4 antagonist, GSK2193874, in elastase-treated WT mice and in AngII-treated ApoE-/- mice caused a significant attenuation of aortic diameter, decrease in pro-inflammatory cytokines (IL-1ß, IL-6, IL-17, MCP-1, MIP-1α, MIP-2, RANTES, and TNF-α), inflammatory cell infiltration (CD3 + T cells, macrophages, and neutrophils), elastic fiber disruption, and an increase in smooth muscle cell α-actin expression compared to untreated mice. Similarly, elastase-treated TRPV4-/- mice had a significant decrease in AAA formation, aortic inflammation, and vascular remodeling compared to elastase-treated WT mice on Day 14. In vitro studies demonstrated that the inhibition of TRPV4 channels mitigates aortic smooth muscle cell-dependent inflammatory cytokine production as well as decreases neutrophil transmigration through aortic endothelial cells. Therefore, our results suggest that TRPV4 antagonism can attenuate aortic inflammation and remodeling via decreased smooth muscle cell activation and neutrophil transendothelial migration during AAA formation.

Single-Photon Emission Computed Tomography Imaging Using Formyl Peptide Receptor 1 Ligand Can Diagnose Aortic Aneurysms in a Mouse Model.

BACKGROUND: Our previous studies showed that neutrophil infiltration and activation plays an important role in the pathogenesis of abdominal aortic aneurysms (AAA). However, there is a lack of noninvasive, inflammatory cell-specific molecular imaging methods to provide early diagnosis of AAA formation. Formyl peptide receptor 1 (FPR1) is rapidly upregulated on neutrophils during inflammation. Therefore, it is hypothesized that the use of cinnamoyl-F-(D)L-F-(D)L-F-K (cFLFLF), a PEGylated peptide ligand that binds FPR1 on activated neutrophils, would permit accurate and noninvasive diagnosis of AAA via single-photon emission computed tomography (SPECT) imaging. MATERIALS AND METHODS: Male C57BL/6 (wild-type) mice were treated with topical elastase (0.4 U/mL type 1 porcine pancreatic elastase) or heat-inactivated elastase (control), and aortic diameter was measured by video micrometry. Comparative histology was performed on Day 14 to assess neutrophil infiltration in aortic tissue. We performed near-infrared fluorescence imaging using c-FLFLF-Cy7 probe on Days 7 and 14 postelastase treatment and measured fluorescence intensity ex vivo in excised aortic tissue. A separate group of animals were injected with 99mTc-c-FLFLF 2 h before SPECT imaging on Day 14 using a SPECT/computed tomography/positron emission tomography trimodal scanner. Coexpression of neutrophils with c-FLFLF was also performed on aortic tissue by immunostaining on Day 14. RESULTS: Aortic diameter was significantly increased in the elastase group compared with controls on Days 7 and 14. Simultaneously, a marked increase in neutrophil infiltration and elastin degradation as well as decrease in smooth muscle integrity were observed in aortic tissue after elastase treatment compared with controls. Moreover, a significant increase in fluorescence intensity of c-FLFLF-Cy7 imaging probe was also observed in elastase-treated mice on Day 7 (approximately twofold increase) and Day 14 (approximately 2.5-fold increase) compared with respective controls. SPECT imaging demonstrated a multifold increase in signal intensity for 99mTc-cFLFLF radiolabel probe in mice with AAA compared with controls on Day 14. Immunostaining of aortic tissue with c-FLFLF-Cy5 demonstrated a marked increase in coexpression with neutrophils in AAA compared with controls. CONCLUSIONS: cFLFLF, a novel FPR1 ligand, enables quantifiable, noninvasive diagnosis and progression of AAAs. Clinical application of this inflammatory, cell-specific molecular probe using SPECT imaging may permit early diagnosis of AAA formation, enabling targeted therapeutic interventions and preventing impending aortic rupture.

Reduced-flow ex vivo lung perfusion to rehabilitate lungs donated after circulatory death.

BACKGROUND: Current ex vivo lung perfusion (EVLP) protocols aim to achieve perfusion flows of 40% of cardiac output or more. We hypothesized that a lower target flow rate during EVLP would improve graft function and decrease inflammation of donation after circulatory death (DCD) lungs. METHODS: A porcine DCD and EVLP model was utilized. Two groups (n = 4 per group) of DCD lungs were randomized to target EVLP flows of 40% (high-flow) or 20% (low-flow) predicted cardiac output based on 100 ml/min/kg. At the completion of 4 hours of normothermic EVLP using Steen solution, left lung transplantation was performed, and lungs were monitored during 4 hours of reperfusion. RESULTS: After transplant, left lung-specific pulmonary vein partial pressure of oxygen was significantly higher in the low-flow group at 3 and 4 hours of reperfusion (3-hour: 496.0 ± 87.7 mm Hg vs. 252.7 ± 166.0 mm Hg, p = 0.017; 4-hour: 429.7 ± 93.6 mm Hg vs. 231.5 ± 178 mm Hg, p = 0.048). Compliance was significantly improved at 1 hour of reperfusion (20.8 ± 9.4 ml/cm H2O vs. 10.2 ± 3.5 ml/cm H2O, p = 0.022) and throughout all subsequent time points in the low-flow group. After reperfusion, lung wet-to-dry weight ratio (7.1 ± 0.7 vs. 8.8 ± 1.1, p = 0.040) and interleukin-1ß expression (927 ± 300 pg/ng protein vs. 2,070 ± 874 pg/ng protein, p = 0.048) were significantly reduced in the low-flow group. CONCLUSIONS: EVLP of DCD lungs with low-flow targets of 20% predicted cardiac output improves lung function, reduces edema, and attenuates inflammation after transplant. Therefore, EVLP for lung rehabilitation should use reduced flow rates of 20% predicted cardiac output.

Cost-Effectiveness of Postoperative Drug Rehabilitation for Injection Drug Users.

BACKGROUND: With the opioid crisis showing no sign of abating, strategies are needed to facilitate postoperative care for endocarditis related to injection drug use (IDU). The current standard, 6 weeks of intravenous antibiotics, yields frequent reoperation and IDU relapse. We examined the cost-effectiveness of inpatient drug rehabilitation (DR) postoperatively to optimize outcomes and costs. METHODS: Two postoperative strategies were assessed: hospital-only care (HC) vs HC plus inpatient DR. Monte Carlo simulation evaluated effectiveness in quality-adjusted life-years (QALY) and cost per patient calculated over a 20-year time horizon in 100,000 iterations. Willingness to pay was set to $100,000/QALY. To determine probabilities of continued postoperative IDU, recurrent infection, and death, best available evidence was combined with institutional data from IDU patients. Baseline probability of postoperative IDU was set to 35% after DR vs 60% after HC, and the cost of inpatient rehabilitation to $30,000. RESULTS: Addition of inpatient DR to standard HC is the favorable strategy, with incremental per-patient cost of $36,920 and 0.93 QALYs gained over 20 years. Sensitivity analysis demonstrates DR is within our willingness-to-pay of $100,000/QALY if postoperative IDU is reduced by at least 7% (from 60% to 53%). CONCLUSIONS: Addition of postoperative inpatient DR for IDU-related endocarditis is cost-effective even if only a modest reduction in IDU is achieved. Collaboration between hospitals and payors to launch pilot programs that provide postoperative addiction treatment and intravenous antibiotics after cardiac operations could dramatically improve endocarditis care.

Porcine Model of Infrarenal Abdominal Aortic Aneurysm.

Large animal models to study abdominal aortic aneurysms are sparse. The purpose of this model is to create reproducible, clinically significant infrarenal abdominal aortic aneurysms (AAA) in swine. To achieve this, we use a combination of balloon angioplasty, elastase and collagenase, and a lysyl oxidase inhibitor, called ß-aminopropionitrile (BAPN), to create clinically significant infrarenal aortic aneurysms, analogous to human disease. Noncastrated male swine are fed BAPN for 7 days prior to surgery to achieve a steady state in the blood. A midline laparotomy is performed and the infrarenal aorta is circumferentially dissected. An initial measurement is recorded prior to aneurysm induction with a combination of balloon angioplasty, elastase (500 units)/collagenase (8000 units) perfusion, and topical elastase application. Swine are fed BAPN daily until terminal procedure on either postoperative day 7, 14, or 28, at which time the aneurysm is measured, and tissue procured. BAPN + surgery pigs are compared to pigs that underwent surgery alone. Swine treated with BAPN and surgery had a mean aortic dilation of 89.9% ± 47.4% at day 7, 105.4% ± 58.1% at day 14, and 113.5% ± 30.2% at day 28. Pigs treated with surgery alone had significantly smaller aneurysms compared to BAPN + surgery animals at day 28 (p < 0.0003). The BAPN + surgery group had macroscopic and immunohistochemical evidence of end stage aneurysmal disease. Clinically significant infrarenal AAA can be induced using balloon angioplasty, elastase/collagenase perfusion and topical application, supplemented with oral BAPN. This model creates large, clinically significant AAA with hallmarks of human disease. This has important implications for the elucidation of AAA pathogenesis and testing of novel therapies and devices for the treatment of AAA. Limitations of the model include variation in BAPN ingested by swine, quality of elastase perfusion, and cost of BAPN.

Murine Surgical Model of Topical Elastase Induced Descending Thoracic Aortic Aneurysm.

According to the Center for Disease Control, aortic aneurysms (AAs) were considered a leading cause of death in all races and both sexes from 1999-2016. An aneurysm forms as a result of progressive weakening and eventual dilation of the aorta, which can rupture or tear once it reaches a critical diameter. Aneurysms of the descending aorta in the chest, called descending thoracic aortic aneurysms (dTAA), make up a large proportion of aneurysm cases in the United States. Uncontained dTAA rupture is almost universally lethal, and elective repair has a high rate of morbidity and mortality. The purpose of our model is to study dTAA specifically, to elucidate the pathophysiology of dTAA and to search for molecular targets to halt the growth or reduce the size of dTAA. By having a murine model to study thoracic pathology precisely, targeted therapies can be developed to specifically test dTAA. The method is based on the placement of porcine pancreatic elastase (PPE) directly on the outer murine aortic wall after surgical exposure. This creates a destructive and inflammatory reaction, which weakens the aortic wall and allows for aneurysm formation over weeks to months. Though murine models possess limitations, our dTAA model produces robust aneurysms of predictable size. Furthermore, this model can be used to test genetic and pharmaceutical targets which may arrest dTAA growth or prevent rupture. In human patients, interventions such as these could help avoid aneurysm rupture, and difficult surgical intervention.

Impact of New Vascular Fellowship Programs on Vascular Surgery Operative Volume of Residents in Associated General Surgery Programs.

BACKGROUND: General surgery (GS) resident vascular surgery (VS) operations have declined significantly in the last 15 years. We hypothesized that initiation of VS fellowship programs (VSFPs) contributes to that decline. This study examined the effect of establishing new VSFPs on VS case volumes of residents in associated GS programs. STUDY DESIGN: General surgery programs were reviewed if associated with VSFPs accredited since July 1, 2002 that had 1 or more matriculants (GS case logs only available since 2002 to 2003). Total VS cases by residents in those programs was analyzed before and after matriculation of first fellow into the associated VSFP. RESULTS: Twenty-two programs were available for analysis. General surgery case-log data were available variably from 0 to 14 years before and 0 to 14 years after first fellows in the associated VSFPs. In 12 programs with 4 years of data before and after matriculation of associated VSFPs' first fellows, VS cases increased from 109.6 ± 32.4 cases to 143.65 ± 78.15 cases in 4 years before matriculation (p = 0.008) of VS fellows and then declined from 143.65 to 114.04 ± 46.97 in 4 years after (p = 0.0134). In all 16 programs with 4 years of data after matriculation of the associated VSFP's first fellow, VS cases declined from 123.37 ± 71.42 to 103.23 ± 44.35 (p = 0.0232). CONCLUSIONS: New VSFPs diminished peak VS operative volume of residents in associated GS programs, thereby contributing to declining national average number of VS cases done by GS residents. Nevertheless, resident VS case volumes remained robust in most GS programs associated with new VSFPs. Additional study is required to determine both resident perception and overall impact of VSFPs on associated GS training.

Preoperative beta blockade is associated with increased rates of 30-day major adverse cardiac events in critical limb ischemia patients undergoing infrainguinal revascularization.

OBJECTIVE: The association between beta blockers and cardiovascular or limb-related outcomes after revascularization for critical limb ischemia (CLI) remains unclear. The objective of this study was to assess the impact of preoperative beta blockade on 30-day major adverse cardiac events (MACEs) and major adverse limb events (MALEs) in patients undergoing infrainguinal revascularization for CLI. We hypothesized that rates of MALEs and MACEs will be higher in patients not receiving preoperative beta blockade. METHODS: The National Surgical Quality Improvement Program vascular targeted file for 2011 to 2014 identified patients receiving beta blockade and undergoing infrainguinal endovascular intervention and open bypass for CLI. Primary outcomes including 30-day MACE (stroke, myocardial infarction [MI], or death) and MALE (untreated loss of patency, reintervention, or amputation) were compared between patients taking and not taking preoperative beta blockers. Multivariate logistic regression identified independent predictors of MACEs and MALEs. RESULTS: A total of 11,785 revascularizations were performed for CLI during the study period (7408 bypasses vs 4377 endovascular interventions). Preoperative beta blockers were used by 7365 patients, including 4541 (61.7%) in the open bypass cohort and 2824 (64.5%) in the endovascular group (P < .01). MACEs and MI were significantly higher in patients with preoperative beta blockers (MACEs, 5.8% vs 3.4% [P < .0001]; MI, 3.1% vs 1.8% [P < .0001]). After controlling for cardiac risk factors, beta blockers independently predicted MACEs (odds ratio [OR], 1.27; P = .03) and MI (OR, 1.36; P = .03) but not stroke (OR, 1.17; P = .58) or 30-day mortality (OR, 1.22; P = .19). Beta-blocker use did not have an effect on MALEs (OR, 0.99; P = .88). CONCLUSIONS: In patients with CLI, preoperative beta blockade was an independent predictor of 30-day MI and MACEs after controlling for other cardiovascular risk factors. Beta blockers did not have an impact on short-term limb-related outcomes. The association between beta blockade and revascularization for CLI deserves further investigation.

A Comparison of Outcomes After Lower Extremity Bypass and Repeat Endovascular Intervention Following Failed Previous Endovascular Intervention for Critical Limb Ischemia.

The optimal approach for repeat revascularization after failed endovascular intervention for critical limb ischemia (CLI) is unclear. This study compared major adverse limb events (MALEs) and major adverse cardiac events (MACEs) between lower extremity bypass (LEB) and repeat endovascular intervention (REI) in patients with prior failed ipsilateral endovascular intervention. American College of Surgeons National Surgical Quality Improvement Program database identified patients undergoing LEB and endovascular intervention for CLI from 2011 to 2014. We compared REI to LEB with single-segment saphenous vein (LEB-SV) and LEB alternative conduit (LEB-alt). Primary outcomes were 30-day MALE and MACE. Multivariate analysis identified independent predictors of MALE and MACE. A total of 1567 revascularizations were performed after failed ipsilateral endovascular intervention (REI: 683 [43.5%], LEB-SV: 570 [36.4%], LEB-alt: 314 [20.0%]). There were 994 and 573 suprageniculate and infrageniculate revascularizations, respectively. Major adverse cardiac events were significantly lower after REI compared to LEB (REI: 15 [2.2%], LEB-SV: 33 [5.8%], LEB-alt: 21 [6.7%], P < .001). Major adverse limb event were not different between groups ( P = .99). In patients with CLI presenting after failed endovascular intervention, REI is associated with lower MACE without an increased risk of MALE compared to LEB. When the anatomy is amenable, REI should be considered a less morbid first option.