A Randomized Comparison of Positional Stability: The EZ-Blocker Versus Left-Sided Double-Lumen Endobronchial Tubes in Adult Patients Undergoing Thoracic Surgery.

OBJECTIVE: To assess if there is a difference in the repositioning rate of the EZ-Blocker versus a left-sided double-lumen endobronchial tube (DLT) in patients undergoing thoracic surgery and one-lung ventilation. DESIGN: Prospective, randomized. SETTING: Single center, university hospital. PARTICIPANTS: One hundred sixty-three thoracic surgery patients. INTERVENTIONS: Patients were randomized to either EZ-Blocker or a DLT. MEASUREMENTS AND MAIN RESULTS: The primary outcome was positional stability of either the EZ-Blocker or a left-sided double-lumen endobronchial tube, defined as the number of repositionings per hour of surgery and one-lung ventilation. Secondary outcomes included an ordinal isolation score from 1 to 3, in which 1 was poor, up to 3, which represented excellent isolation, and a visual analog postoperative sore throat score (0-100) on postoperative days (POD) one and two. Rate of repositionings per hour during one-lung ventilation and surgical manipulation in left-sided cases was similar between the two devices: 0.08 ± 0.15 v 0.11 ± 0.3 (p = 0.72). In right-sided cases, the rate of repositioning was higher in the EZ-Blocker group compared with DLT: 0.38 ± 0.65 v 0.09 ± 0.21 (p = 0.03). Overall, mean isolation scores for the EZ-Blocker versus the DLT were 2.76 v 2.92 (p = 0.04) in left-sided cases and 2.70 v 2.83 (p = 0.22) in right-sided cases. Median sore throat scores for left sided cases were 0 v 5 (p = 0.13) POD one and 0 v 5 (p = 0.006) POD two for the EZ-Blocker and left-sided DLT, respectively. CONCLUSION: For right-sided procedures, the positional stability of the EZ-Blocker is inferior to a DLT. In left-sided cases, the rate of repositioning for the EZ-Blocker and DLT are not statistically different.

Disparate outcomes in patients with colorectal cancer: effect of race on long-term survival.

BACKGROUND: Increasing evidence suggests significant disparity in colorectal cancer outcomes between black and white patients. Contributing factors may include advanced tumor stage at diagnosis, differences in treatment, more aggressive tumor biology, access to care, and patient comorbidity. HYPOTHESIS: Disparities in colorectal cancer outcomes exist despite similar objective measures of treatment. DESIGN AND SETTING: Ten-year retrospective review of all patients with colorectal cancer using tumor registries at a city hospital (n = 83) and a university medical center (n = 585) in the same city. We assessed stage at diagnosis; curative surgical resection; use of adjuvant treatment; overall, disease-free, and stage-specific survival; and socioeconomic status. Patients with nonwhite, nonblack ethnicity (4% overall) were excluded. Differences in stage and treatments were compared using the chi(2) test, and median survival rates were compared using log-rank tests. RESULTS: Significantly more black patients were treated at the city hospital (53.0%) vs the university medical center (10.6%) (P<.001). No differences were identified in stage distribution or treatments received between hospitals or between black and white patients. Significantly worse survival was noted among patients treated at the city hospital (2.1 vs 5.3 years; P<.001) and among black patients treated at both institutions (city hospital: 1.4 vs 2.1 years, and university hospital: 3.2 vs 5.7 years; P<.001 for both). Disease-free survival rates showed similar significant reductions for black patients at both institutions. There was no association between survival and socioeconomic status at either institution. CONCLUSION: The marked reductions in overall and disease-free survival for black patients with colorectal cancer do not seem to be related to variation in treatment but may be due to biologic factors or non-cancer-related health conditions.

Hepatic cryoablation-induced multisystem injury: bioluminescent detection of NF-kappaB activation in a transgenic mouse model.

Hepatic injury from cryoablation has been associated with multisystem injury, including adult respiratory distress syndrome, renal insufficiency, and coagulopathy; but the responsible mechanisms have not been well defined. In the present study we investigated the role of the transcription factor NF-kappaB in the multiorgan inflammatory response to hepatic cryoablation utilizing a novel in vivo system for determining NF-kappaB activity. Using transgenic mice expressing photinus luciferase under the control of the 5' HIV-LTR (an NF-kappaB-dependent promoter), we measured luciferase activity in the liver, lungs, and kidneys as a marker for NF-kappaB activity. Luciferase production was determined by in vivo bioluminescence and by luciferase assays of tissue homogenates. After measurement of basal luciferase activity, mice were treated with 35% hepatic cryoablation or sham laparotomy and injected with luciferin (0.75 mg/mouse). Photon emission from the liver, lungs, and kidneys was measured at multiple time points. Hepatic cryoablation induced a significant increase in photon emission by the liver, lungs, and kidneys, which correlated with markedly increased luciferase activity measured from each organ after death. Lung lavage 4 hours after cryoablation showed neutrophilic lung inflammation with increased MIP-2 levels compared with sham surgery. These findings demonstrate that 35% hepatic cryoablation is associated with NF-kappaB activation in the remnant liver and multiple distant sites, and may be causally related to the multisystem injury that is seen after direct liver injury.

Indications and limitations of liver transplantation for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a common cause of cancer-related death worldwide, yet remains difficult to treat, with dismal overall long-term survival rates. Recent strategies using liver transplantation for carefully selected patients with stage I and II HCC and cirrhosis have shown promising results, with 5-year survival rates comparable to survival rates for transplantation patients without malignancy. Currently, however, limited resources and a severe organ shortage make liver transplantation an option for only a limited number of patients with HCC in the United States. Future studies must document the long-term success of this therapy and improve methods for disease control before and after transplantation.

The role of [18F]fluorodeoxyglucose positron emission tomography imaging in the evaluation of hepatocellular carcinoma.

It has been well established that hepatocellular carcinomas (HCCs) accumulate [18F]fluorodeoxyglucose (FDG) to varying degrees; this is thought to be due to differing amounts of FDG-6-phosphatase activity. The purpose of this study was to evaluate the impact of FDG imaging on the management of patients diagnosed with hepatocellular carcinoma. We conducted a retrospective review of the clinical data of 91 consecutive patients diagnosed with HCC who underwent FDG-positron emission tomography (PET) imaging between August 1993 and March 2001. The patients were divided into two groups. In Group one 67 of 91 (74%) patients were evaluated for proven but untreated hepatic lesions using PET. In Group two the remaining 24 patients (26%) were referred for evaluation of HCC recurrence but did not have prior PET. The FDG images were acquired with two dedicated PET tomographs [Siemens ECAT 933, CTI (Knoxville, TN) and GE Advance, General Electric Medical Systems (Milwaukee, WI)] one hour after the intravenous administration of 10 mCi of FDG. Tumor biopsy or resection specimens were available for review from 34 patients and were evaluated for histologic grade, presence of cirrhosis, tumor necrosis, and intratumoral fibrosis. In group one 43 of 67 (64%) of the HCCs accumulated FDG. Sixteen of the 43 patients in whom FDG was accumulated had multiple subsequent FDG-PET scans either for monitoring therapy or for detection of recurrence. FDG-PET imaging had an impact on the management of 20 of these patients: by guiding the biopsy at the metabolically active site of a large necrotic tumor (one), by identifying distant metastases (five), by monitoring the response to treatment with hepatic chemoembolization and guiding additional regional therapy (12), and by detecting recurrence (two). In group two recurrence and/or metastases were demonstrated with FDG-PET imaging in six of 24 (25%) patients, three of whom had multiple subsequent FDG-PET scans to monitor their treatment. Higher histopathologic grade and intratumoral fibrosis but not necrosis or cirrhosis correlated with PET positivity. In this study only 64 per cent of HCCs accumulated FDG. Despite this limitation FDG-PET imaging remains a useful tool in the diagnosis and treatment of HCC. FDG-PET imaging had a clinically significant impact in 26 of 91 (28%) patients with HCC. This includes detection of unsuspected metastatic disease in high-risk patients-including liver transplant candidates-and monitoring response to hepatic-directed therapy. FDG-PET should be considered as part of the workup and management of selected patients with HCC.

Biliary reconstruction is enhanced with a collagen-polyethylene glycol sealant.

Bile leaks occur in up to 27 per cent of liver transplant patients after biliary reconstruction. Synthetic sealants have not been investigated for these biliary procedures. We performed a randomized controlled study to evaluate a novel absorbable polyethylene glycol/collagen biopolymer sealant (CT3 Surgical Sealant) after incomplete end-to-end choledochocholedochostomy (CDCD) in pigs. Pigs (n = 18) underwent transection of the common bile duct and incomplete CDCD over a T-tube, leaving a one-sixth circumferential defect anteriorly. Animals were randomly assigned to treatment (CDCD with sealant, n = 9) or control (no sealant, n = 9). Drains were used to monitor leak volume and bilirubin (bili) concentration. Cholangiography was performed on postoperative day 3. Leaks were defined as drain bili/serum bill > 3, total drain output > 10 mL/kg, and/or extravasation on cholangiography. Animals sacrificed at 3 and 8 weeks (n = 4 and n = 5 from each group, respectively) underwent pathologic examination of the CDCD site. Statistical methods included Student's t test, chi2, linear regression, and analysis of variance procedures. The control group had a higher drain output rate over the first 4 postoperative days than the treatment group (P < 0.05, analysis of variance). Five of nine (56%) control and one of nine (11%) treatment animals had a bile leak (P < 0.05, chi2). There was no major inflammatory response to the sealant versus controls. We conclude that CT3 is effective in decreasing biliary leaks in an incomplete CDCD porcine model with no major adverse pathologic changes. This sealant should be considered for trials for biliary reconstruction in humans.

Multi-organ inflammation after hepatic cryoablation in BALB/c mice.

BACKGROUND: There is increasing evidence that injury to the liver can precipitate or exaggerate lung injury. We have previously shown that hepatic cryoablation (cryo) causes activation of nuclear factor (NF)-kappaB, cytokinemia (tumor necrosis factor-alpha, Mouse Macrophage Inflammatory Protein-2 [MIP-2]), and lung inflammation in transgenic HLL (5'HIV-LTR-Luciferase gene) mice and in Sprague-Dawley rats. It has been reported that BALB/c mice are susceptible to traumatic injury and are active immune responders. We tested whether activation of NF-kappaB and the development of multiple-organ inflammation in response to hepatic injury from 35% cryo were demonstrable in the BALB/c mouse. METHODS: BALB/c mice (n = 9) were anesthetized, and midline laparotomy was performed. Cryoablation was performed with careful isolation of adjacent structures to avoid inadvertent organ injury to the gastrointestinal tract. A freeze-thaw cycle of the left lobe of the liver was induced, encompassing approximately 35% (by weight). Animals were sacrificed at 1, 2, 4, and 24 h after cryoablation. Serum was collected via IVC puncture and liver, lungs, and kidneys were harvested and freeze-clamped. Two animals were sacrificed without undergoing cryo surgery to serve as a baseline control. NF-kappaB activity was monitored by electrophoretic mobility shift assays. MIP-2 levels and Mouse KC levels from tissue and serum were measured using enzyme-linked immunosorbent assay. Organs were submitted for histological review. We characterized lung inflammation induced by cryosurgery by measuring total and differential cell counts in lung lavage fluid 4 h after hepatic cryoablation. RESULTS: After cryo, NF-kappaB activation was demonstrated in the 1, 2, and 4-h time points by electrophoretic mobility shift assay in the liver and lungs. Mouse KC and MIP-2 levels increased from baseline, peaked at the 4-h time point, and returned to baseline after 24 h in both liver and lung. Lung lavage 4 h after cryoablation showed increased total cells and neutrophilic lung inflammation. CONCLUSIONS: BALB/c mice demonstrate evidence of multi-organ inflammation in response to 35% hepatic cryo. These data demonstrate that this model provides for assessment of liver-mediated multi-system inflammation after direct liver injury.

Prevention of gallstone formation in morbidly obese patients undergoing rapid weight loss: results of a randomized controlled pilot study.

INTRODUCTION: An increased risk of gallstone (GS) formation has been linked to obesity and to episodes of rapid and significant weight loss. Previous reports have suggested that bile salt therapy (ursodeoxycholic acid) or prostaglandin inhibition (ibuprofen) may prevent gallstone formation in this high-risk group. The purpose of this study was to investigate GS prevention following bariatric surgery. DESIGN: Randomized double blind controlled trial. METHODS: Sixty patients without gallstones preoperatively (gender, 9 male, 51 female; average preop wt, 349.6 lb; mean age, 38 years) were randomly assigned to receive urso (600 mg/day, n = 20), ibuprofen (600 mg/d, n = 20), or placebo (n = 20). At the time of standard open gastric bypass, intraoperative ultrasonography confirmed the absence of stones or microcalculi, and bile samples were collected via puncture of the gallbladder for bile lipid analysis. Following recovery and resumption of a bariatric diet, study medication was prescribed for the first 6 months postop. Gallbladder emptying and GS formation were assessed using ultrasonograms preop and at 3, 6, 9, and 12 months postop (gallbladder emptying following a high-fat liquid test meal was assessed preop, and at 3 and 6 months postop). RESULTS: Forty-one (68.3%, 8 male, 33 female) of the original 60 patients completed all phases of the study (15 urso, 15 ibuprofen, 11 placebo). The average weight loss was 98.5 +/- 7.2 lb over the 12-month period following bariatric surgery. Twenty-nine (71%) of 41 patients who completed the study developed GS. Of those who formed stones, 12 (41%) developed symptomatic GS and 8/12 (67%) underwent cholecystectomy (4 refused operation). Preoperative gallbladder emptying studies showed no differences in emptying between groups (urso 29%, ibuprofen 32%, and placebo 30%). There was no correlation found between the cholesterol saturation index (CSI mean 205.15, range 67-360) and the incidence of GS. There was a statistical difference (P < 0.01) between the ursodeoxycholic acid group and the ibuprofen group with respect to the incidence of stone formation. There was correlation between weight loss (mean 99 lb, range 21-278 lb) and GS formation, in that patients who lost more weight had a greater tendency to form gallstones. Complete medical compliance was achieved in only 17/60 (28%) of patients originally enrolled. CONCLUSIONS: This pilot study confirms the high incidence of gallstone formation (71% of assessed patients) associated with rapid weight loss in patients undergoing gastric bypass. Despite active enrollment in a supervised prevention trial, the two therapies investigated to reduce gallstone formation were not efficacious, likely because compliance with medical therapy was poor. These findings highlight the significant risk of gallstone formation in this patient cohort even when prevention strategies are utilized.

Modulation of endotoxin-induced NF-kappa B activation in lung and liver through TNF type 1 and IL-1 receptors.

We investigated the requirement for tumor necrosis factor-alpha (TNF-alpha) and interleukin (IL)-1 receptors in the pathogenesis of the pulmonary and hepatic responses to Escherichia coli lipopolysaccharide (LPS) by studying wild-type mice and mice deficient in TNF type 1 receptor [TNFR1 knockout (KO)] or both TNF type 1 and IL-1 receptors (TNFR1/IL-1R KO). In lung tissue, NF-kappaB activation was similar among the groups after exposure to aerosolized LPS. After intraperitoneal injection of LPS, NF-kappaB activation in liver was attenuated in TNFR1 KO mice and further diminished in TNFR1/IL-1R KO mice; however, in lung tissue, no impairment in NF-kappaB activation was found in TNFR1 KO mice and only a modest decrease was found in TNFR1/IL-1R KO mice. Lung concentrations of KC and macrophage-inflammatory peptide 2 were lower in TNFR1 KO and TNFR1/IL-1R KO mice after aerosolized and intraperitoneal LPS. We conclude that LPS-induced NF-kappaB activation in liver is mediated through TNF-alpha- and IL-1 receptor-dependent pathways, but, in the lung, LPS-induced NF-kappaB activation is largely independent of these receptors.