Increasing tumor length is associated with regional lymph node metastases and decreased survival in esophageal cancer.

BACKGROUND: Although tumor length has received little attention for staging of esophageal cancer, it may be a valid prognostic feature for node positivity and survival. METHODS: Through retrospective review of a prospective institutional database, esophageal cancer patients who completed esophagectomy without neoadjuvant chemoradiation were analyzed. Pathologic tumor lengths were compared with node positivity and survival through a zero-inflated negative binomial regression model and multivariable Cox proportional hazards model, respectively. RESULTS: Between January 2000 and July 2015, 98 patients met inclusion, criteria (84% male, median age of 65, 90% adenocarcinoma). Median tumor length was 2.5 cm with each 1-cm increase in length increasing the odds of node positivity (odds ratio 3.55, 95% confidence interval 1.50 to 8.40, P = .004) and decreasing overall survival (hazards ratio 1.18, 95% confidence interval 1.06 to 1.32, P < .003). CONCLUSION: This study suggests an association among tumor length, lymph node metastasis, as well as overall survival in esophageal cancer patients who have not received neoadjuvant chemoradiotherapy.

Characteristics predicting clinical improvement and cure following laparoscopic adrenalectomy for primary aldosteronism in a large cohort.

BACKGROUND: Surgical resection is the standard of care for unilateral adrenal adenomas and hyperplasia resulting in primary aldosteronism (PA). Resolution of PA following surgery is variable and some patients continue to require some or all of their antihypertensives. Prior studies have investigated factors contributing to "cure" of PA (defined as no hypertension [HTN] medications required postoperatively). These models are a tool in patient selection, yet fail to consider the benefit of some reduction in medications, resolution of hypokalemia, or reduction in blood pressure which may improve long-term cardiovascular and renal outcomes. We sought to investigate factors contributing to postoperative improvement or complete resolution following surgery. METHODS: This is a retrospective review of prospectively collected data on 58 adrenalectomies performed for PA from December 1999 to April 2013 at a single center. Patient demographics, PA characteristics, labs, and imaging studies were evaluated, as well as operative characteristics. Mean systolic and diastolic blood pressures were calculated over several visits after discharge, and postoperative antihypertensive regimen was recorded. Patients were stratified by cured vs not cured and then again by improved vs not improved based on differences in pre- and postoperative values. Aldosteronoma Resolution Score was also calculated for each patient. RESULTS: Median age was 52.6 years, with 44.8% women and an average duration of HTN of 13.5 years. Average body mass index (BMI) was 31.5 kg/m(2); 74% of the lesions were adenomas. Patients with complications had higher BMIs than those without (36.9 vs 28.7 kg/m(2), P = .02). In comparing improved (n = 42, 72%) vs not improved (n = 16, 28%) patients, preoperative systolic blood pressure (147.5 vs 159.7 mm Hg, P = .047) and serum creatinine (.94 vs 1.32 mg/dL, P = .016) were higher in the not improved group. Cured (n = 13) vs not cured (n = 45) patients differed in terms of BMI (27.4 vs 32.7, P = .009), duration of HTN (9.1 vs 14.9 years, P = .020), and number of preoperative antihypertensives (2.1 vs 3.7, P = .002). Aldosteronoma Resolution Score was significantly higher in cured patients (3.2 vs 1.0, P < .01). CONCLUSIONS: A significant number of patients who are not cured by adrenalectomy for PA will still benefit from surgery. Obesity, duration of HTN, and number of medications may predict cure, yet fail to detect a population of patients with overall improvement. Attention to serum creatinine may help in distinguishing this population of patients.

Short esophagus.

In the presence of long-standing and severe gastroesophageal reflux disease, patients can develop various complications, including a shortened esophagus. Standard preoperative testing in these patients should include endoscopy, esophagography, and manometry, whereas the objective diagnosis of a short esophagus must be made intraoperatively following adequate mediastinal mobilization. If left untreated, it is a contributing factor to the high recurrence rate following fundoplications or repair of large hiatal hernias. A laparoscopic Collis gastroplasty combined with an antireflux procedure offers safe and effective therapy.

Thromboelastogram-guided enoxaparin dosing does not confer protection from deep venous thrombosis: a randomized controlled pilot trial.

BACKGROUND: The incidence of deep venous thrombosis (DVT) remains high in general surgery and trauma patients despite widespread prophylaxis with enoxaparin. A recent study demonstrated decreased incidence of DVT if patients on enoxaparin had a change in R time (ΔR) of greater than 1 minute when heparinase-activated thromboelastography (TEG) was compared with normal TEG. We hypothesized that using ΔR-guided dosing would result in decreased DVT rates. METHODS: A prospective, randomized controlled trial was performed at a Level 1 trauma center. Both trauma and general surgery patients were included. Upon enrollment, demographic data including age, sex, body mass index, and Acute Physiology and Chronic Health Evaluation II score were obtained. Enrolled patients were randomized to standard (30 mg twice a day) or TEG-guided dosing. Dose-adjusted patients underwent daily enoxaparin titration to achieve an ΔR of 1 minute to 2 minutes. Venous thromboembolism screening was performed per institutional protocol. Antithrombin III (AT-III) and anti-Xa levels were drawn at peak enoxaparin concentrations. RESULTS: A total of 87 patients were enrolled. There was no difference in demographic data between the groups. No pulmonary emboli were identified. The control group had a DVT rate of 16%, while the experimental group had a rate of 14% (p = nonsignificant). The experimental group's median enoxaparin dosage, 50 mg twice a day, was significantly higher than that of the control (p < 0.01). TEG ΔR was not different between the control and experimental groups. Beginning at Day 3, anti-Xa levels were higher in the experimental group (p < 0.05). There was no difference in AT-III activity between the two groups; 67% of the patients demonstrated AT-III deficiency. CONCLUSION: TEG adjusted enoxaparin dosing led to significant increases in anti-Xa activity, which did not correlate with a decreased DVT rate. Failure to reduce the DVT rate and increase ΔR despite increased dosing and increased anti-Xa activity is consistent with the high rate of AT-III deficiency detected in this study cohort. These data suggest that the future of DVT prevention may not lie in the optimization of low molecular weight heparin therapy but rather in compounds that increase antithrombin directly or operate independently of the AT-III pathway. LEVEL OF EVIDENCE: Therapeutic study, level III.

The International Normalized Ratio overestimates coagulopathy in stable trauma and surgical patients.

BACKGROUND: The international normalized ratio (INR) was developed to assess adequacy of Coumadin dosing. Its use has been generalized to guide fresh frozen plasma (FFP) therapy in stable patients. Thrombelastography (TEG) is a whole-blood assay measuring the viscoelastic properties of the clot in near real time. This study hypothesized that INR does not reflect coagulopathy and should not be used to guide FFP therapy in stable trauma and surgical patients. METHODS: Prospective observational data were collected from stable trauma and surgical patients (n = 106) who received FFP transfusions. Pretransfusion and posttransfusion blood samples were obtained to assess complete blood count, standard coagulation parameters (INR, partial thromboplastin time, fibrinogen and D-dimer), soluble clotting factors (II, V, VII, VIII, IX, X, XI, XII, proteins C and S) and TEG. Data were analyzed using a Mann-Whitney U-test. Significance was defined as p < 0.05. RESULTS: A total of 262 U of FFP were transfused, with 78% of 106 patients receiving two or more units. Despite a reduction in INR, median TEG values remained within normal limits, while clotting factor levels retained adequate function to produce normal clotting before and following FFP transfusion. CONCLUSION: The use of FFP in this population did not affect coagulation status in a clinically relevant manner based on TEG values and coagulation factor function. INR is not a predictor of coagulopathy and should not be used to guide coagulation factor replacement in stable trauma and surgical patients. LEVEL OF EVIDENCE: Diagnostic study, level III.

Uncontrolled hemorrhagic shock results in a hypercoagulable state modulated by initial fluid resuscitation regimens.

BACKGROUND: Previous studies have shown large-volume resuscitation modulates coagulopathy and inflammation. Our objective was to analyze the effects of initial bolus fluids used in military and civilian settings on coagulation and inflammation in a prospective, randomized, blinded trial of resuscitation of uncontrolled hemorrhage. METHODS: Fifty swine were anesthetized, intubated, and ventilated and had monitoring lines placed. A Grade V liver injury was performed followed by 30 minutes of hemorrhage. After 30 minutes, the liver was packed, and randomized fluid resuscitation was initiated during a 12-minute period with 2 L of normal saline, 2 L of lactated Ringer's solution, 250 mL of 7.5% saline with 3% Dextran, 500 mL of Hextend, or no fluid (NF). Animals were monitored for 2 hours after injury. Thrombelastograms (TEGs), prothrombin time (PT), partial thromboplastin time, fibrinogen as well as serum interleukin 6, interleukin 8, and tumor necrosis factor α levels were drawn at baseline and after 1 hour and 2 hours. RESULTS: The NF group had less posttreatment blood loss compared with other groups (p < 0.01). Blood loss was similar in the other groups. TEG R values in each group decreased from baseline at 1 and 2 hours (p < 0.02). The groups receiving 2 L of normal saline, 250 mL of 7.5% saline with 3% Dextran, or 500 mL of Hextend had lower TEG maximum amplitude values compared with NF group (p < 0.02). All fluids except lactated Ringer's solution resulted in significant increases in PT compared with NF, whereas all fluids resulted in significant decreases in fibrinogen compared with NF (p < 0.02). Fluid resuscitation groups as well as NF group demonstrated significant increases in inflammatory cytokines from baseline to 1 hour and baseline to 2 hours. There were no significant differences in inflammatory cytokines between groups at 2 hours. CONCLUSION: Withholding fluid resulted in the least significant change in PT, fibrinogen, and maximum amplitude and in the lowest posttreatment blood loss. Resuscitation with different initial fluid resuscitation strategies did not result in increased proinflammatory mediators compared with animals that did not receive fluid.

Chitosan based advanced hemostatic dressing is associated with decreased blood loss in a swine uncontrolled hemorrhage model.

BACKGROUND: The purpose of this study was to compare standard gauze (SG) and advanced hemostatic dressings in use by military personnel in a no-hold model. METHODS: A randomized, controlled trial was conducted using 36 swine. Animals underwent femoral arteriotomy, followed by 60 seconds of uncontrolled hemorrhage. After hemorrhage, packing with 1 of 3 dressings-SG, Combat Gauze (CG), or Celox Rapid gauze (XG)-and a 500-mL bolus of Hextend were initiated. Pressure was not held after packing, and animals were followed for 120 minutes. Physiologic parameters were monitored continuously, and electrolyte and hematologic laboratory assessments were performed before injury and 30 and 120 minutes after injury. Dressing failure was determined if bleeding occurred outside the wound. RESULTS: All animals survived to study end. Baseline characteristics were similar between groups. No statistical difference was seen in initial blood loss or dressing success rate (SG, 10 of 12; CG, 10 of 12; and XG, 12 of 12). Secondary blood loss was significantly less with XG (median, 12.8 mL; interquartile range, 8.8 to 39.7 mL) compared with SG (median, 44.7 mL; interquartile range, 17.8 to 85.3 mL; P = .02) and CG (median, 31.9 mL; interquartile range, 18.6 to 69.1 mL; P = .05). Packing time was significantly shorter with XG (mean, 37.1 ± 6.2 seconds) compared with SG (mean, 45.2 ± 6.0 seconds; P < .01) and CG (mean, 43.5 ± 5.6 seconds; P = .01). CONCLUSIONS: XG demonstrated shorter application time and decreased secondary blood loss in comparison with both SG and CG. These differences may be of potential benefit in a care-under-fire scenario.

Thrombelastography-identified coagulopathy is associated with increased morbidity and mortality after traumatic brain injury.

BACKGROUND: The purpose of this study was to determine the relationship between coagulopathy and outcome after traumatic brain injury. METHODS: Patients admitted with a traumatic brain injury were enrolled prospectively and admission blood samples were obtained for kaolin-activated thrombelastogram and standard coagulation assays. Demographic and clinical data were obtained for analysis. RESULTS: Sixty-nine patients were included in the analysis. A total of 8.7% of subjects showed hypocoagulability based on a prolonged time to clot formation (R time, > 9 min). The mortality rate was significantly higher in subjects with a prolonged R time at admission (50.0% vs 11.7%). Patients with a prolonged R time also had significantly fewer intensive care unit-free days (8 vs 27 d), hospital-free days (5 vs 24 d), and increased incidence of neurosurgical intervention (83.3% vs 34.9%). CONCLUSIONS: Hypocoagulability as shown by thrombelastography after traumatic brain injury is associated with worse outcomes and an increased incidence of neurosurgical intervention.

Hextend and 7.5% hypertonic saline with Dextran are equivalent to Lactated Ringer's in a swine model of initial resuscitation of uncontrolled hemorrhagic shock.

BACKGROUND: The optimal fluid strategy for the early treatment of trauma patients remains highly debated. Our objective was to determine the efficacy of an initial bolus of resuscitative fluids used in military and civilian settings on the physiologic response to uncontrolled hemorrhagic shock in a prospective, randomized, blinded animal study. METHODS: Fifty anesthetized swine underwent central venous and arterial catheterization followed by celiotomy. Grade V liver injury was performed, followed by 30 minutes of uncontrolled hemorrhage. Then, liver packing was completed, and fluid resuscitation was initiated over 12 minutes with 2 L normal saline (NS), 2 L Lactated Ringer's (LR), 250 mL 7.5% hypertonic saline with 3% Dextran (HTS), 500 mL Hextend (HEX), or no fluid (NF). Animals were monitored for 2 hours postinjury. Blood loss after initial hemorrhage, mean arterial pressure (MAP), tissue oxygen saturation (StO2), hematocrit, pH, base excess, and lactate were measured at baseline, 1 hour, and 2 hours. RESULTS: NF group had less post-treatment blood loss compared with other groups. MAP and StO2 for HEX, HTS, and LR at 1 hour and 2 hours were similar and higher than NF. MAP and StO2 did not differ between NS and NF, but NS resulted in decreased pH and base excess. CONCLUSIONS: Withholding resuscitative fluid results in the least amount of posttreatment blood loss. In clinically used volumes, HEX and HTS are equivalent to LR with regard to physiologic outcomes and superior to NF. NS did not provide a measurable improvement in outcome compared with NF and resulted in increased acidosis.

High ratios of plasma and platelets to packed red blood cells do not affect mortality in nonmassively transfused patients.

BACKGROUND: Administration of high transfusion ratios in patients not requiring massive transfusion might be harmful. We aimed to determine the effect of high ratios of fresh frozen plasma (FFP) and platelets (PLT) to packed red blood cells (PRBC) in nonmassively transfused patients. METHODS: Records of 1,788 transfused trauma patients who received <10 units of PRBC in 24 hours at 23 United States Level I trauma centers were reviewed. The relationship between ratio category (low and high) and in-hospital mortality was assessed with propensity-adjusted multivariate proportional hazards models. RESULTS: At baseline, patients transfused with a high FFP:PRBC ratio were younger, had a lower Glasgow Coma Scale score, and a higher Injury Severity Score. Those receiving a high PLT:PRBC ratio were older. The risk of in-hospital mortality did not vary significantly with FFP:PRBC ratio category. Intensive care unit (ICU)-free days, hospital-free days, and ventilator-free days did not vary significantly with FFP:PRBC ratio category. ICU-free days and ventilator-free days were significantly decreased among patients in the high (≥1:1) PLT:PRBC category, and hospital-free days did not vary significantly with PLT:PRBC ratio category. The analysis was repeated using 1:2 as the cutoff for high and low ratios. Using this cutoff, there was still no difference in mortality with either FFP:PRBC ratios or platelet:PRBC ratios. However, patients receiving a >1:2 ratio of FFP:PRBCs or a >1:2 ratio PLT:PRBCs had significantly decreased ICU-free days and ventilator-free days. CONCLUSIONS: FFP:PRBC and PLT:PRBC ratios were not associated with in-hospital mortality. Depending on the threshold analyzed, a high ratio of FFP:PRBC and PLT:PRBC transfusion was associated with fewer ICU-free days and fewer ventilator-free days, suggesting that the damage control infusion of FFP and PLT may cause increased morbidity in nonmassively transfused patients and should be rapidly terminated when it becomes clear that a massive transfusion will not be required.