Shin E.J.,Johns Hopkins Hospital |
Amateau S.K.,Johns Hopkins Hospital |
Kim Y.,Korea University |
Gabrielson K.L.,Johns Hopkins Hospital |
And 6 more authors.
Gastrointestinal Endoscopy | Year: 2012
Background: Cryotherapy is a method of endoscopic mucosal ablation that involves delivery of a cryogen to result in tissue destruction by extreme low temperature. Its effects are influenced by the dosage of cryogen and thawing of ice. There are limited data on the tissue effects of multiple freeze and thaw cycles of carbon dioxide (CO2) cryotherapy on GI tissues. Objective: To investigate the extent of tissue injury due to escalating doses of CO 2 cryotherapy on the esophagus, stomach, and colon of pigs. Design: Animal experiment. Intervention: Varying doses of CO2 cryotherapy with increasing number of freeze-thaw cycles were applied to each site. The animals were allowed to survive for 48 hours. Main Outcome Measurements: Depth of tissue injury assessed in blinded fashion by varying doses of cryotherapy on a defined area of porcine esophagus, stomach, and colon. Results: There was a dose-dependent relationship of CO2 cryogen and depth of injury (P =.0001 and P =.002, respectively). In the stomach, the dose-response relationship was significant (P =.007), but the average grades of injury across the various doses were lower when compared with the esophagus at comparable cryogen doses (P =.0004). The estimated depth of tissue injury from the mucosal surface in the porcine esophagus and colon tissue ranged from 1.2 to 2.5 mm and 1.3 to 2.5 mm, respectively. Limitations: The study was performed in a normal porcine model. Conclusion: There was a dose-dependent relationship between the dose of CO2 cryotherapy and the depth of tissue injury in the porcine esophagus, stomach, and colon. © 2012 American Society for Gastrointestinal Endoscopy. Source
Cohen L.B.,Mount Sinai Hospital |
Cattau E.,Memphis Gastroenterology Group |
Goetsch A.,Clinical Research Associates |
Shah A.,Shah Associates |
And 3 more authors.
Journal of Clinical Gastroenterology | Year: 2010
Goals: This double-blind, multicenter study evaluated the safety and efficacy of intravenous fospropofol (6.5mg/kg vs. 2mg/kg) for moderate sedation in patients undergoing colonoscopy. Methods: In all, 314 patients 18 years (American Society of Anesthesiologists PS1 to PS3) were randomized to receive fospropofol 2mg/kg, fospropofol 6.5-mg/kg, or midazolam 0.02mg/kg, after pretreatment with intravenous fentanyl 50mcg. Supplemental doses of study medication were permitted to achieve a Modified Observer's Assessment of Alertness/Sedation scale score ≤4 and to enable the investigator to begin a procedure. The study end points included sedation success, recovery, memory retention, physician satisfaction, and safety. Results: Sedation success was higher in the fospropofol 6.5mg/kg versus 2mg/kg group (87% vs. 26%; P<0.001) and was 69% in the midazolam group. Patients in the 6.5-mg/kg group were significantly less likely to remember being awake during the procedure (51% vs. 100% in the 2-mg/kg group, P<0.001; 60% for the midazolam group). Patients in the fospropofol groups had similar memory retention (70% and 82% for the 6.5mg/kg and 2mg/kg groups, respectively) compared with 41% for the midazolam group. Mean physician satisfaction scores were higher in the fospropofol 6.5-mg/kg group (7.7) than the 2-mg/kg group (4.5), P<0.001. Most adverse events were mild to moderate in intensity; the most common treatment-related adverse events were paresthesias (68% vs. 60%) and pruritus (16% vs. 26%) in the fospropofol 6.5 and 2mg/kg groups, respectively. Conclusions: The fospropofol 6.5-mg/kg dosing regimen was well tolerated and effective for sedation during colonoscopy and was associated with higher rates of sedation success, memory retention, and physician satisfaction than the fospropofol 2-mg/kg dose. © 2010 by Lippincott Williams & Wilkins. Source
Sastry A.V.,Beth Israel Deaconess Medical Center |
Sastry A.V.,Center for Digestive Health |
Abbadessa B.,Beth Israel Deaconess Medical Center |
Wayne M.G.,Beth Israel Deaconess Medical Center |
And 2 more authors.
World Journal of Surgery | Year: 2015
The incidence of cancer in choledochal cysts (CCs) in adults was calculated to determine the timing and need for surgery. In 78 publications (1996-2010), 434 of 5780 reported CCs patients had cancer. Cholangiocarcinoma (70.4 %) and gallbladder cancer (23.5 %) were the most common malignancies. Only nine malignancies were reported before age 18 (0.42 %). In contrast, the incidence of malignancy in adults was 11.4 %. The median age for diagnosis of cancer was 42 years, and the incidence increased with each decade. © Société Internationale de Chirurgie 2014. Source
Sharma V.K.,Center for Digestive Health
Techniques in Gastrointestinal Endoscopy | Year: 2010
The incidence of esophageal adenocarcinoma is rising at an epidemic rate. Barrett's esophagus (BE) is its only known precursor lesion and is an ideal target for endoprevention of esophageal adenocarcinoma. Recent advances in endoscopic therapy, especially radiofrequency ablation (RFA) using the HALO system have renewed interest in ablative therapies for the management of BE. RFA uses a bipolar electrode array to deliver thermal energy to the metaplastic and dysplastic Barrett's tissue for large-area circumferential and small-area focal ablation. Multiple prospective uncontrolled trials, case series, and registries have consistently shown safety and effectiveness of RFA in treating all stages of BE. A large multicenter sham-controlled trial showed that in patients with either low-grade or high-grade dysplasia, RFA is effective in ablating esophageal intestinal metaplasia and dysplasia and preventing progression to higher grades of dysplasia and cancer. In addition, cost-effectiveness models have shown ablation may be a cost-effective strategy for the management of all stages of BE. This article is a review of technical background of RFA using the HALO system and is a summary of the data on its current applications for the treatment of BE. © 2010. Source
Ratziu V.,University Pierre and Marie Curie |
Sheikh M.Y.,University of California at San Francisco |
Sanyal A.J.,Virginia Commonwealth University |
Lim J.K.,Yale University |
And 15 more authors.
Hepatology | Year: 2012
In nonalcoholic steatohepatitis (NASH), the extent of hepatocyte apoptosis correlates with disease severity. Reducing hepatocyte apoptosis with the selective caspase inhibitor GS-9450 has a potential for altering the course of the liver disease. In this phase 2, double-blind study, 124 subjects with biopsy-proven NASH were randomized to once-daily placebo or 1, 5, 10, or 40 mg GS-9450 for 4 weeks. Absolute and percent changes from baseline in ALT levels, AST levels, and caspase-3-cleaved cytokeratin (CK)-18 fragments at week 4 were assessed by an analysis of covariance model with adjustment for baseline values. In the 40-mg group, mean (SD) ALT decreased by 47 (43) U/L from baseline to week 4 (P < 0.0001 versus placebo), and the proportion of subjects with normal ALT increased from 0% to 35% at week 4. In the 40-mg group, mean AST decreased by 13 U/L from baseline (not significant), and the proportion with normal AST increased from 20% at baseline to 48% at week 4. By week 4, mean CK-18 fragment levels had decreased to 393 (723) U/L in the GS-9450 10-mg group and 125 (212) U/L in the 40-mg group, but these reductions were not statistically significant. No serious adverse events were reported during treatment, and the percentage of subjects with at least one treatment-emergent grade 3 or 4 laboratory abnormality ranged from 11.5% to 17% across the GS-9450 treatment groups versus 35% in the placebo group. Conclusion: GS-9450 treatment induced significant reductions in ALT levels in NASH patients. Reductions in CK-18 fragment levels also occurred, although they were not statistically significant. At appropriate therapeutic indices, selective caspase inhibitors may be a promising treatment option in patients with NASH. © 2011 American Association for the Study of Liver Diseases. Source