Evolving management of early stage pancreatic adenocarcinoma in older patients.

BACKGROUND: Due to the aging population, the number of older patients diagnosed with pancreatic ductal adenocarcinoma (PDAC) will continue to rise. STUDY DESIGN: Utilizing the NCDB from 2010 to 2016, patients with early stage, clinically node negative PDAC who were ≥70 years old and had a Whipple were identified. Multivariable logistic regressions were used to determine independent factors for R0 resection and NAT. Cox-proportional-hazards regression analyses examined for the impact of NAT on the risk of death. RESULTS: Of 5086 patients, 51.7% received upfront surgery + adjuvant therapy (UFS + AT), followed by 29.9% UFS only, and the remainder NAT. NAT significantly improved OS compared to a combined cohort of those that had UFS ± AT. NAT retained its independent survival benefit when compared to only patients that had UFS + AT. CONCLUSION: For older patients diagnosed with early stage PDAC, NAT was associated with improved R0 resection rates and a significant survival benefit when compared to the current standard of care.

Systemic Therapy Is Associated with Improved Oncologic Outcomes in Resectable Stage II/III Intrahepatic Cholangiocarcinoma: An Examination of the National Cancer Database over the Past Decade.

Limited evidence-based management guidelines for resectable intrahepatic cholangiocarcinoma (ICC) currently exist. Using a large population-based cancer registry; the utilization rates and outcomes for patients with clinical stages I-III ICC treated with neoadjuvant chemotherapy (NAT) in relation to other treatment strategies were investigated, as were the predictors of treatment regimen utilization. Oncologic outcomes were compared between treatment strategies. Amongst 2736 patients, chemotherapy utilization was low; however, NAT use increased from 4.3% to 7.2% (p = 0.011) over the study period. A higher clinical stage was predictive of the use of NAT, while higher pathologic stage and margin-positive resections were predictive of the use of adjuvant therapy (AT). For patients with more advanced disease, the receipt of NAT or AT was associated with significantly improved survival compared to surgery alone (cStage II, p = 0.040; cStage III, p = 0.003). Furthermore, patients receiving NAT were more likely to undergo margin-negative resections compared to those treated with AT (72.5% vs. 62.6%, p = 0.027), despite having higher-risk tumors. This analysis of treatment strategies for resectable ICC suggests a benefit for systemic therapy. Prospective and randomized studies evaluating the sequencing of treatments for patients with high-risk resectable ICC are needed.

Treatment Utilization and Outcomes for Locally Advanced Rectal Cancer in Older Patients.

Importance: The number of older patients (80 years and older) diagnosed with locally advanced rectal cancer (LARC) is expected to increase. Although current guidelines recommend neoadjuvant chemoradiation therapy (NACRT) followed by resection, little is known about management and outcomes in this older population. Objective: To assess the trends in management of older patients diagnosed with LARC who had a surgical resection. Design, Setting, and Participants: Patients 80 years and older who had a surgical resection for LARC were identified in the 2004-2016 National Cancer Database. Patients were grouped based on therapy sequence: (1) surgery followed by adjuvant therapy (AT), ie, chemotherapy or radiation; (2) surgery alone; or (3) NACRT followed by surgical resection. Data were analyzed in May 2021. Exposures: NACRT followed by surgery, and surgery with or without AT. Main Outcomes and Measures: Overall survival (OS) was assessed using Kaplan-Meier analyses with inverse probability of treatment weighting (IPTW) and Cox proportional hazards regression were performed to examine the association of NACRT with the risk of death. Results: Of 3868 patients with LARC who underwent surgical resection, 2042 (52.8%) were male, and the mean (SD) age was 83.4 (3.0) years. A total of 2273 (58.8%) received NACRT followed by surgical resection. Factors independently associated with NACRT were more recent diagnosis, age 80 to 85 years (vs 86 years and older), fewer comorbidities, larger tumors, and node-positive disease. The Kaplan-Meier analyses with IPTW showed that 3-year and 5-year OS for NACRT (3-year: 68.9%; 95% CI, 67.0-70.8; 5-year: 51.1%; 95% CI, 49.0-53.4) vs surgery with AT (3-year: 64.4%; 95% CI, 59.0-70.2; 5-year: 43.0%; 95% CI, 37.4-49.5) vs surgery alone (3-year: 55.8%; 95% CI, 52.0-60.0; 5-year: 34.7%; 95% CI, 30.8-39.0) was significantly different (P < .001). After adjusting for confounders, patients who received NACRT were more likely to undergo an R0 resection (adjusted odds ratio, 2.16; 95% CI, 1.62-2.88), which independently improved OS (P < .001). Moreover, receipt of NACRT was independently associated with a 25% decreased risk of death (adjusted hazard ratio, 0.75; 95% CI, 0.69-0.82) compared with alternative treatment sequences. Conclusions and Relevance: Approximately 40% of older patients with LARC did not receive the current standard of care. In this cohort, NACRT was associated with a higher likelihood of an R0 resection and improved OS. Clinicians should advocate for receipt of NACRT in older patients with LARC.

Predicting Regional Lymph Node Recurrence in the Modern Age of Tumor-Positive Sentinel Node Melanoma: The Role of the First Postoperative Ultrasound.

BACKGROUND: The Multicenter Selective Lymphadenectomy Trial II (MSLT-II) led to a change in the management of tumor-positive sentinel lymph nodes (SLNs) from completion node dissection (CLND) to nodal observation. This study aimed to evaluate prognostic factors for predicting sentinel node basin recurrence (SNBR) using data from MSLT-II trial participants. METHODS: In MSLT-II, 1076 patients were treated with observation. Patients were included in the current study if they had undergone a post-sentinel node basin ultrasound (PSNB-US) within 4 months after surgery. The study excluded patients with positive SLN by reverse transcription-polymerase chain reaction (RT-PCR) or incomplete SLN pathologic data. Primary tumor, patient, PSNB-US, and SLN characteristics were evaluated. Multivariable regression analyses were performed to determine independent prognostic factors associated with SNBR. RESULTS: The study enrolled 737 patients: 193 (26.2%) patients with SNBR and 73 (9.9%) patients with first abnormal US. The patients with an abnormal first US were more likely to experience SNBR (23.8 vs. 5.0%). In the multivariable analyses, increased risk of SNBR was associated with male gender (adjusted hazard ratio [aHR], 1.38; 95% confidence interval [CI], 1.00-1.9; p = 0.049), increasing Breslow thickness (aHR, 1.10; 95% CI, 1.01-1.2; p = 0.038), presence of ulceration (aHR, 1.93; 95% CI, 1.42-2.6; p < 0.001), sentinel node tumor burden greater than 1 mm (aHR, 1.91; 95% CI, 1.10-3.3; p = 0.022), lymphovascular invasion (aHR, 1.53; 95% CI, 1.00-2.3; p = 0.048), and presence of abnormal PSNB-US (aHR, 4.29; 95% CI, 3.02-6.1; p < 0.001). CONCLUSIONS: The first postoperative US together with clinical and pathologic factors may play an important role in predicting SNBR.

Prognostic indicators for undifferentiated carcinoma with/without osteoclast-like giant cells of the pancreas.

BACKGROUND: Undifferentiated carcinoma of the pancreas (UPC) is a rare malignancy. There are no standardized guidelines for treatment. Current management has been extrapolated from smaller reviews. METHODS: 858 patients with UPC were identified in the 2004-2017 NCDB. Kaplan-Meier method followed by Cox proportional-hazards regression examined independent prognostic factors associated with overall survival (OS). Logistic regression analyses were performed to determine independent predictors of surgical intervention and the status of surgical resection by histologic subtype. RESULTS: Patients with osteoclast-like giant cells (OCLGC) had a longer median OS compared to those without (aHR 0.52: 95% CI 0.41-0.67). Of the non-OCLGC subtypes, pleomorphic large cell demonstrated the shortest median OS (2.4 months). Surgical resection was associated with improved survival in all histologies except for pleomorphic cell carcinoma. R0 resection and negative lymph nodes were independently associated with an improved OS. CONCLUSION: This is the largest database review published to date on UCP. OCLGC histology is associated with an improved survival compared to those without OCLGC. Of the non-OCLGC subtypes, pleomorphic large cell is associated with the shortest overall survival. Surgical resection is associated with a significant survival advantage for all histologies except for pleomorphic cell carcinoma.

Development of atrial fibrillation following trauma increases short term risk of cardiovascular events.

CONTEXT: New onset atrial fibrillation (AF) is associated with poor outcomes in several different patient populations. OBJECTIVES: To assess the effect of developing AF on cardiovascular events such as myocardial infarction (MI) and cerebrovascular accident (CVA) during the acute index hospitalization for trauma patients. METHODS: The Healthcare Cost and Utilization Project State Inpatient Databases for California and Florida were used to identify adult trauma patients (18 years of age or older) who were admitted between 2007 and 2010. After excluding patients with a history of AF and prior history of cardiovascular events, patients were evaluated for MI, CVA, and death during the index hospitalization. A secondary analysis was performed using matched propensity scoring based on age, race, and preexisting comorbidities. RESULTS: During the study period, 1,224,828 trauma patients were admitted. A total of 195,715 patients were excluded for a prior history of AF, MI, or CVA. Of the remaining patients, 15,424 (1.5%) met inclusion criteria and had new onset AF after trauma. There was an associated increase in incidence of MI (2.9 vs. 0.7%; p<0.001), CVA (2.6 vs. 0.4%; p<0.001), and inpatient mortality (8.5 vs. 2.1%; p<0.001) during the index hospitalization in patients who developed new onset AF compared with those who did not. Cox proportional hazards regression demonstrated an increased risk of MI (odds ratio [OR], 2.35 [2.13-2.60]), CVA (OR, 3.90 [3.49-4.35]), and inpatient mortality (OR, 2.83 [2.66-3.00]) for patients with new onset AF after controlling for all other potential risk factors. CONCLUSIONS: New onset AF in trauma patients was associated with increased incidence of myocardial infarction (MI), cerebral vascular accident (CVA), and mortality during index hospitalization in this study.

Red blood cell distribution width and outcome in trauma patients.

Context: Red blood cell distribution width (RDW) has been used to predict mortality during infection and inflammatory diseases. It also been purported to be predictive of mortality following traumatic injury. Objective: To identify the role of RDW in predicting mortality in trauma patients. We also sought to identify the role of RDW in predicting the development of sepsis in trauma patients. Methods: A retrospective observational study was performed of the medical records for all adult trauma patients admitted to Loyola University Medical Center from 2007 to 2014. Patients admitted for fewer than four days were excluded. Admission, peak, and change from admission to peak (Δ) RDW were recorded to determine the relationship with in-hospital mortality. Patient age, development of sepsis during the hospitalization, admission to the intensive care unit (ICU), and discharge disposition were also examined. Results: A total of 9,845 patients were admitted to the trauma service between 2007 and 2014, and a total of 2,512 (25.5%) patients fit the inclusion criteria and had both admission and peak values available. One-hundred twenty (4.6%) died while in the hospital. RDW values for all patients were (mean [standard deviation, SD]): admission 14.09 (1.88), peak 15.09 (2.34), and Δ RDW 1.00 (1.44). Admission, peak, and Δ RDW were not significant predictors of mortality (all p>0.50; hazard ratio [HR], 1.01-1.03). However, trauma patients who eventually developed sepsis had significantly higher RDW values (admission RDW: 14.27 (2.02) sepsis vs. 13.98 (1.73) no sepsis, p<0.001; peak RDW: 15.95 (2.55) vs. 14.51 (1.97), p<0.001; Δ RDW: 1.68 (1.77) vs. 0.53 (0.91), p<0.001). Conclusion: Admission, peak, and Δ RDW were not associated with in-hospital mortality in adult trauma patients with a length of stay (LOS) ≥four days. However, the development of sepsis in trauma patients is closely linked to increased RDW values and in-hospital mortality.

Does resection improve overall survival for intrahepatic cholangiocarcinoma with nodal metastases?

BACKGROUND: The potential benefit of surgical resection of intrahepatic cholangiocarcinoma in patients with locoregionally advanced disease has not been definitively determined. METHODS: The National Cancer Database was queried to identify patients with clinical evidence of node-positive intrahepatic cholangiocarcinoma. Resected patients were stratified by margin status and lymph node ratio (nodes positive to nodes harvested). Risk of death was determined using Cox regression models and Kaplan-Meier survival functions. RESULTS: A total of 1,425 patients with T(any)N1M0 intrahepatic cholangiocarcinoma were identified. Two hundred twelve (14.9%) underwent surgical resection. On multivariable Cox regression, R0 resection afforded a survival benefit regardless of lymph node ratio (lymph node ratio > 0.5: hazard ratio 0.466, 95% confidence interval 0.304-0.715; lymph node ratio ≤ 0.5: hazard ratio 0.444, 95% confidence interval 0.322-0.611), whereas a survival benefit was only seen in R1 patients with lymph node ratio ≤ 0.5 (hazard ratio 0.470, 95% confidence interval 0.316-0.701). On Kaplan-Meier, median survival was 11.6 months with chemotherapy, 15.7 months with R0 resection in lymph node ratio > 0.5, and 22.2 months with R0 resection in lymph node ratio ≤ 0.5 (P < .001). DISCUSSION: Margin negative resection is associated with a risk-adjusted survival benefit for patients with clinically N1 intrahepatic cholangiocarcinoma regardless of the degree of regional lymph node involvement.

Total gastrectomy in patients with gastric adenocarcinoma: Is there an advantage to the minimally invasive approach?

BACKGROUND: Previous evaluations of the oncologic efficacy of minimally invasive approaches to total gastrectomy in gastric adenocarcinoma have been limited by sample size and duration of follow-up. METHODS: We queried the National Cancer Database to identify patients undergoing robotic and laparoscopic or open total gastrectomy for gastric adenocarcinoma between 2010 and 2015. Propensity score matching was used to adjust for patient, tumor, and treating facility factors. Kaplan-Meier survival functions were used to compare overall survival. Secondary outcomes included margin status, lymph node sampling, mortality, readmission, and length of stay. RESULTS: In the study, 3,213 (72.2%) patients underwent open total gastrectomy; 1,238 (27.8%) minimally invasive total gastrectomy. Patients undergoing minimally invasive total gastrectomy were more likely to be treated at academic (49.5% vs 57.8%, P < .05) and high-volume centers (21.6% vs 28.4%, P < .05). Propensity score matching yielded 1,238 open and 1,238 minimally invasive well-matched total gastrectomies. Minimally invasive was associated with a decreased median length of stay (10 vs 9 days; P < .01). Rates of positive surgical margins, 30-day readmission, 90-day mortality and overall survival were identical between matched cohorts (P > .1). CONCLUSION: Minimally invasive approaches to total gastrectomy provide perioperative oncologic outcomes and overall survival rates that are identical to those for open total gastrectomy but are associated with reduced length of stay.

Long-Term Hemodynamic Effects After Carotid Artery Revascularization.

OBJECTIVE: The baroreceptor at the carotid body plays an important role in hemodynamic autoregulation. Manipulation of the baroreceptor during carotid endarterectomy (CEA) or radial force from carotid artery angioplasty and/or stenting (CAS) may cause both intraoperative and postoperative hemodynamic instability. The purpose of this study is to evaluate the long-term effects of CEA and CAS on blood pressure (BP), heart rate (HR), and subsequent changes on antihypertensive medications. METHODS: A retrospective chart review was performed to identify patients who underwent CEA or CAS between 2009 and 2015 at a single tertiary care institution. Baseline demographics and comorbidities were recorded. Operative details of the carotid artery endarterectomy and the use of balloon angioplasty during the CAS were analyzed. Hemodynamic parameters such as BP, HR, and antihypertensive medication requirement were evaluated at 3, 6, 12, 24, and 36 months. RESULTS: A total of 289 patients were identified. The average age was 70.6 years old, and males constituted 64.0%. All patients had moderate (>50%) to severe (>70%) carotid stenosis. Of those, 111 (40.5%) patients were symptomatic. Systolic BP (mm Hg) of CAS and CEA were similar over the entire follow-up period. Heart rate (beats/min) remained stable postoperatively. A reduced number of antihypertensive medications was observed in the CAS cohort during the first postoperative year when compared to the preoperative baseline: 2.03 at preop, 1.77 ( P < .01) at 3 months, 1.78 ( P = .02) at 6 months, 1.77 ( P = .02) at 12 months, 1.86 ( P = .09) at 24 months, and 2.03 ( P = =.50) at 36 months. Logistic regression analysis identified that CAS (odds ratio [OR]: 2.52, confidence interval [CI]: 1.09-5.83) and multiple (>2) antihypertensive medication use at baseline (OR: 5.89, CI: 2.62-13.26) were predictors for a reduction in the number of antihypertensive medications following carotid revascularization. CONCLUSION: Surgical intervention for carotid stenosis poses a risk of postoperative hemodynamic dysregulation. Although postoperative BP and HR remained relatively stable after both CAS and CEA, the number of postoperative antihypertensive medications was reduced in the CAS cohort for the first postoperative year when compared to baseline. Patients with multiple antihypertensive agents undergoing CAS should have close postoperative BP monitoring and should be monitored for a possible reduction in their antihypertensive medication regimen.

Impact and treatment success of new-onset atrial fibrillation with rapid ventricular rate development in the surgical intensive care unit.

BACKGROUND: Atrial fibrillation (AF) with rapid ventricular rate (RVR; heart rate >100) in noncardiac postoperative surgical patients is associated with poor outcomes. The objective of this study was to evaluate the practice patterns of AF management in a surgical intensive care unit to determine practices associated with rate and rhythm control and additional outcomes. MATERIALS AND METHODS: Adult patients (≥18 y) admitted to the surgical intensive care unit (SICU) from June 2014 to June 2015 were retrospectively screened for the development of new-onset AF with RVR. Demographics, hospital course, evaluation and treatment of AF with RVR, and outcome were evaluated and analyzed. RESULTS: Thousand seventy patients were admitted to the SICU during the study period; 33 met inclusion criteria (3.1%). Twenty-six patients (79%) had rate and rhythm control within 48 h of AF with RVR onset. ß-Blockers were the most commonly used initial medication (67%) but were successful at rate and rhythm control in only 27% of patients (6/22). Amiodarone had the highest rate of success if used initially (5/6, 83%) and secondarily (11/13, 85%). Failure to control rate and rhythm was associated with a greater likelihood of comorbidities (100% versus 57%; P = 0.06). CONCLUSIONS: New-onset AF with RVR in the noncardiac postoperative patient is associated with a high mortality (21%). Amiodarone is the most effective treatment for rate and rhythm control. Failure to establish rate and rhythm control was associated with cardiac comorbidities. These results will help to form future algorithms for the treatment of AF with RVR in the SICU.

Effects of the Kv7 voltage-activated potassium channel inhibitor linopirdine in rat models of haemorrhagic shock.

Recently, we demonstrated that Kv7 voltage-activated potassium channel inhibitors reduce fluid resuscitation requirements in short-term rat models of haemorrhagic shock. The aim of the present study was to further delineate the therapeutic potential and side effect profile of the Kv7 channel blocker linopirdine in various rat models of severe haemorrhagic shock over clinically relevant time periods. Intravenous administration of linopirdine, either before (1 or 3 mg/kg) or after (3 mg/kg) a 40% blood volume haemorrhage, did not affect blood pressure and survival in lethal haemorrhage models without fluid resuscitation. A single bolus of linopirdine (3 mg/kg) at the beginning of fluid resuscitation after haemorrhagic shock transiently reduced early fluid requirements in spontaneously breathing animals that were resuscitated for 3.5 hours. When mechanically ventilated rats were resuscitated after haemorrhagic shock with normal saline (NS) or with linopirdine-supplemented (10, 25 or 50 µg/mL) NS for 4.5 hours, linopirdine significantly and dose-dependently reduced fluid requirements by 14%, 45% and 55%, respectively. Lung and colon wet/dry weight ratios were reduced with linopirdine (25/50 µg/mL). There was no evidence for toxicity or adverse effects based on measurements of routine laboratory parameters and inflammation markers in plasma and tissue homogenates. Our findings support the concept that linopirdine-supplementation of resuscitation fluids is a safe and effective approach to reduce fluid requirements and tissue oedema formation during resuscitation from haemorrhagic shock.

Pharmacological modulation of C-X-C motif chemokine receptor 4 influences development of acute respiratory distress syndrome after lung ischaemia-reperfusion injury.

Activation of C-X-C motif chemokine receptor 4 (CXCR4) has been reported to result in lung protective effects in various experimental models. The effects of pharmacological CXCR4 modulation on the development of acute respiratory distress syndrome (ARDS) after lung injury, however, are unknown. Thus, we studied whether blockade and activation of CXCR4 influences development of ARDS in a unilateral lung ischaemia-reperfusion injury rat model. Anaesthetized, mechanically ventilated animals underwent right lung ischaemia (series 1, 30 minutes; series 2, 60 minutes) followed by reperfusion for 300 minutes. In series 1, animals were treated with vehicle or 0.7 µmol/kg of AMD3100 (CXCR4 antagonist) and in series 2 with vehicle, 0.7 or 3.5 µmol/kg ubiquitin (non-cognate CXCR4 agonist) within 5 minutes of reperfusion. AMD3100 significantly reduced PaO2 /FiO2 ratios, converted mild ARDS with vehicle treatment into moderate ARDS (PaO2 /FiO2 ratio<200) and increased histological lung injury. Ubiquitin dose-dependently increased PaO2 /FiO2 ratios, converted moderate-to-severe into mild-to-moderate ARDS and reduced protein content of bronchoalveolar lavage fluid (BALF). Measurements of cytokine levels (TNFα, IL-6, IL-10) in lung homogenates and BALF showed that AMD3100 reduced IL-10 levels in homogenates from post-ischaemic lungs, whereas ubiquitin dose-dependently increased IL-10 levels in BALF from post-ischaemic lungs. Our findings establish a cause-effect relationship for the effects of pharmacological CXCR4 modulation on the development of ARDS after lung ischaemia-reperfusion injury. These data further suggest CXCR4 as a new drug target to reduce the incidence and attenuate the severity of ARDS after lung injury.

Kv7 voltage-activated potassium channel inhibitors reduce fluid resuscitation requirements after hemorrhagic shock in rats.

BACKGROUND: Recent evidence suggests that drugs targeting Kv7 channels could be used to modulate vascular function and blood pressure. Here, we studied whether Kv7 channel inhibitors can be utilized to stabilize hemodynamics and reduce resuscitation fluid requirements after hemorrhagic shock. METHODS: Anesthetized male Sprague-Dawley rats were instrumented with arterial and venous catheters for blood pressure monitoring, hemorrhage and fluid resuscitation. Series 1: Linopirdine (Kv7 channel blocker, 0.1-6 mg/kg) or retigabine (Kv7 channel activator, 0.1-12 mg/kg) were administered to normal animals. Series 2: Animals were hemorrhaged to a MAP of 25 mmHg for 30 min, followed by fluid resuscitation with normal saline (NS) to a MAP of 70 mmHg until t = 75 min. Animals were treated with single bolus injections of vehicle, linopirdine (1-6 mg/kg), XE-991 (structural analogue of linopirdine with higher potency for channel blockade, 1 mg/kg) prior to fluid resuscitation. Series 3: Animals were resuscitated with NS alone or NS supplemented with linopirdine (1.25-200 µg/mL). Data were analyzed with 2-way ANOVA/Bonferroni post-hoc testing. RESULTS: Series 1: Linopirdine transiently (10-15 min) and dose-dependently increased MAP by up to 15%. Retigabine dose-dependently reduced MAP by up to 60%, which could be reverted with linopirdine. Series 2: Fluid requirements to maintain MAP at 70 mmHg were 65 ± 34 mL/kg with vehicle, and 57 ± 13 mL/kg, 22 ± 8 mL/kg and 22 ± 11 mL/kg with intravenous bolus injection of 1, 3 and 6 mg/kg linopirdine, respectively. XE-991 (1 mg/kg), reduced resuscitation requirements comparable to 3 mg/kg linopirdine. Series 3: When resuscitation was performed with linopirdine-supplemented normal saline (NS), fluid requirements to stabilize MAP were 73 ± 12 mL/kg with NS alone and 72 ± 24, 61 ± 20, 36 ± 9 and 31 ± 9 mL/kg with NS supplemented with 1.25, 6.25, 12.5 and 200 µg/mL linopirdine, respectively. CONCLUSIONS: Our data suggest that Kv7 channel blockers could be used to stabilize blood pressure and reduce fluid resuscitation requirements after hemorrhagic shock.

New onset postoperative atrial fibrillation predicts long-term cardiovascular events after gastrectomy.

BACKGROUND: Recent evidence suggests transient postoperative atrial fibrillation leads to future cardiovascular events, even in noncardiac surgery. The long-term effects of postoperative atrial fibrillation in gastrectomy patients are unknown. METHODS: The Healthcare Cost and Utilization Project State Inpatient Databases identified patients undergoing gastrectomy for malignancy between 2007 and 2010. Patients were matched by propensity scores based on various factors. Adjusted Kaplan-Meier and Cox proportional hazards models assessed the effect of postoperative atrial fibrillation on cardiovascular events. RESULTS: A higher incidence of cardiovascular events occurred over the 1st year in patients who developed postoperative atrial fibrillation. Cox proportional hazards regression confirmed an increased risk of cardiovascular events in postoperative atrial fibrillation patients. CONCLUSIONS: Our results demonstrate that patients undergoing gastrectomy for malignancy who develop postoperative atrial fibrillation are at increased risk of cardiovascular events within 1 year. Physicians should be vigilant in assessing postoperative atrial fibrillation, given the increased risk of cardiovascular morbidity.

Calcium channel blockers and angiotensin-converting enzyme inhibitors may be associated with altered atherosclerotic plaque size and morphology.

Correlations of atherosclerotic plaque attributes with clinical presentation have not been studied in peripheral arterial disease (PAD). The aim of the current study was to identify clinical variables associated with alterations in PAD plaque morphology. Thirty-one patients underwent intravascular ultrasonography (IVUS) at the time of arteriography for symptomatic PAD. IVUS data were analyzed with radiofrequency techniques for quantification of plaque composition, plaque volume, and total vessel volume. Associations between plaque characteristics and clinical variables were evaluated. Univariable and multivariable analyses were performed using t-test, Pearson correlations, F-tests, and analysis of variance. Calcium (Ca2+) channel blocker use was associated with a smaller total atherosclerotic plaque burden (44.2 +/- 2.7 vs 52.9 +/- 2.5%; p < .05), and decreased fibrous plaque content (18.2 +/- 1.8% vs 24.0 +/- 1.9%; p < .05). Angiotensin-converting enzyme (ACE) inhibitor use, however, was associated with a larger total atherosclerotic plaque burden (58.3 +/- 2.2% vs 42.9 +/- 2.1%; p < .01) and larger fibrous plaque content (27.2 +/- 2.0% vs 17.7 +/- 1.6%; p < .001). Multivariable analysis was performed to evaluate which factors may differentially impact the response variable measurements of plaque volume to vessel volume. Based on this model, those without the use of an antihyperlipidemic agent or ACE inhibitor had an average total atherosclerotic plaque burden of 47.7%. Those on an antihyperlipidemic agent had an average decrease of 7.0% (p < .05), whereas those on ACE inhibitors had an average increase of 16.2% from the baseline value (p < .001). The use of calcium channel blockers is associated with significantly decreased atherosclerotic plaque burden and decreased fibrous plaque content, whereas the use of ACE inhibitors was associated with an increase in plaque burden and an increased fibrous plaque content. The use of these medications in PAD may alter plaque morphology with the potential to affect clinical outcomes.

Arterial calcification increases in distal arteries in patients with peripheral arterial disease.

The aim of this study was to determine if significant differences in plaque composition exist between the popliteal and tibial vessels in patients with severe peripheral arterial disease (PAD). Forty-four patients with PAD required either above-knee (n = 38), below-knee (n = 5), or through-knee (n = 1) amputation for pedal sepsis/gangrene. The 51 vessels (anterior tibial, n = 9; posterior tibial, n = 10; peroneal, n = 3; popliteal, n = 29) were obtained and underwent intravascular ultrasound (IVUS) evaluation ex vivo within 24 hr of amputation. Sequential IVUS data were obtained at known intervals throughout the vessel length and then analyzed with radiofrequency techniques for quantification of plaque composition, plaque volume, and total vessel volume. Plaque composition was categorized as fibrous, fibro-fatty, necrotic core, and dense calcium. Clinical data were obtained via review of electronic records at the time of amputation. Two-sided t-tests were performed to compare components within each plaque. Results are expressed as mean percentage +/- standard error of the mean. Tibial vessels had more dense calcium within these plaques than popliteal arteries (33.8 +/- 5.6% vs. 10.6 +/- 1.9%, p < 0.001). Consequently, distal vessels had less fibro-fatty and fibrous plaque than popliteal arteries (7.7 +/- 1.4% vs. 13.1 +/- 1.2%, p < 0.005; 42.4 +/- 4.7% vs. 61.4 +/- 2.2%, p < 0.001, respectively). Necrotic core plaque composition was found to be similar when comparing tibial versus popliteal arteries (16.1% vs. 14.9%, p = nonsignificant). Clinical factors including diabetes, hyperlipidemia, and chronic renal insufficiency were not associated with plaque composition differences using a univariate analysis. As we progress distally in the arterial tree of patients with PAD, calcium plaque content increases with decreasing burden of fibro-fatty plaque. Clinical and demographic factors, with the exception of smoking, were not found to be associated with atherosclerotic plaque composition.

Angiography underestimates peripheral atherosclerosis: lumenography revisited.

PURPOSE: To compare angiograms, considered the gold standard for diagnostic imaging of peripheral arterial disease (PAD), to the corresponding histological sections of popliteal and tibial vessels obtained after amputation to determine if angiography fails to define atheroma burden in "normal appearing" arteries in patients with PAD. METHODS: Between 2004 and 2006, 69 patients underwent amputation of a lower extremity for severe tissue loss, gangrene, or pedal sepsis precluding limb salvage. Popliteal and tibial vessels were harvested, perfusion-fixed, and analyzed histologically. Thirty-four of these patients had pre-amputation angiography during attempted salvage procedures. Angiograms with patent or minimally diseased vessel segments (n = 19) were assessed for stenoses, diameter, and calcification by 3 vascular surgeons (n = 72 evaluations). These results were compared to corresponding cross-sectional histological slides (n = 66) in a blinded manner. RESULTS: Angiograms performed prior to above-knee (n = 9) or below-knee (n = 10) amputation revealed 24 stenoses with a mean (+/-SD) diameter-reducing stenosis of 19.5%+/-15.2%. Corresponding histological cross sections revealed greater linear stenoses measured via boundaries of the internal elastic lamina (IEL stenosis, 28.9%+/-20.2%, p = 0.003 versus angiography) or via boundaries of the external elastic membrane (vessel stenosis, 43.1%+/-15.2%, p<0.0001). Stenosis calculated by area methods (IEL area) were greater and measured 39.2%+/-24.2% (p<0.0001) and 60.9%+/-15.2% (vessel area, p<0.0001). Popliteal arteries had greater discrepancy in stenosis measurement than tibial arteries (18.5%+/-14.6% versus 34.9%+/-21.0%, p = 0.0005). However, evaluations of tibial arteries for concentricity of plaque (44% versus 69%, p = 0.08) and calcification grade (1.6 versus 2.2, p = 0.002) by angiography were discordant with histological analyses. Measurement of arterial diameter by histology for popliteal arteries (6.2+/-0.9 mm) and tibial arteries (3.1+/-0.7 mm) was greater than angiographic diameter determination (p<0.001). CONCLUSION: Angiography provides information on luminal characteristics of peripheral arteries but severely underestimates the extent of atherosclerosis in patients with PAD even in "normal appearing" vessels.