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.
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.
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).
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.
Summary
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.
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.
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.
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.
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.
Summary
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.
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.
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.
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.
Our data suggest that Kv7 channel blockers could be used to stabilize blood pressure and reduce fluid resuscitation requirements after hemorrhagic shock.
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.
Chemokine (C-X-C motif) receptor 4 (CXCR4) agonists have been shown to protect lung endothelial barrier function in vitro. In vivo effects of CXCR4 modulation on lung endothelial permeability are ...unknown. Here we tested the effects of the CXCR4 agonist ubiquitin and the antagonist AMD3100 on lung vascular permeability and cytokine concentrations in a rat hemorrhage model. Animals were hemorrhaged (mean arterial blood pressure 30 mmHg for 30 min), treated with vehicle, ubiquitin (0.7 and 3.5 µmol/kg) or AMD3100 (3.5 µmol/kg), and resuscitated with crystalloids. Evans blue extravasation was employed to quantify lung vascular permeability. Ubiquitin dose-dependently reduced Evans blue extravasation into the lung. AMD3100 increased Evans blue extravasation. With AMD3100, TNFalpha levels in lung homogenates were increased; while TNFalpha levels were lower with ubiquitin, these differences did not reach statistical significance. Our findings suggest that CXCR4 regulates lung vascular permeability and further point towards CXCR4 as a drug target to confer lung protection during resuscitation from traumatic-hemorrhagic shock.
The potential benefit of surgical resection of intrahepatic cholangiocarcinoma in patients with locoregionally advanced disease has not been definitively determined.
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.
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).
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.
New onset atrial fibrillation (AF) is associated with poor outcomes in several different patient populations.
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.
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.
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.
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.
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.
PDF
