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Preoperative application of CPSI-2364 per os attenuates inflammatory reactions in the tunica muscularis and prevents postoperative ileus in swine
ALIMENTARY TRACT II defecation, several laboratory parameters were applied. After 24 hours, swine were killed and inflammatory activity in the tunica muscularis of the small bowel was measured using a myeloperoxidase assay. Furthermore, smooth muscle contractility was examined in an in vitro organ bath. Gastrointestinal transit was measured by radiographical detection of radiopaque beads in vivo.
Protective effect of methylprednisolone on warm ischemia-reperfusion injury in a cholestatic rat liver Gokulakkrishna Subhas MD, MRCS, Aditya Gupta MD, Daniel Bakston MD, Boris Silberberg MD, Catherine Lobocki MS, MT, Lee Andrus LVT, LAT, BIS, Melissa Decker LVT, LAT, Vijay K Mittal MD, FACS, Michael J Jacobs MD, FACS Providence Hospital and Medical Centers, Southfield, MI
RESULTS: In CPSI-2364–treated swine, myeloperoxidase activity was significantly reduced compared with the placebo group (placebo, 254.2 ⫾ 87.7; CPSI-2364, 102,9 ⫾ 38.3 U/mg tissue). In addition, the onset of defecation was earlier after CPSI-2364 treatment. Functional studies showed an improved contractility of jejunal muscularis strips (placebo, 0.98 ⫾ 0.62; CPSI-2364, 1.91 ⫾ 1.29 g/mm2/s) and an accelerated gastrointestinal transit time in the CPSI-2364 group (geometric center: placebo, 7.67 ⫾ 4.26; CPSI2364, 13 ⫾ 0.66). Laboratory parameters and clinical examination showed no signs of organ disturbances after drug treatment.
INTRODUCTION: Cholestasis is associated with an increased risk of postoperative morbidity and mortality in patients who undergo liver surgery. Cholestasis has been identified as a risk factor for oxidative stress, and it potentially enhances postischemic-reperfusion (IR) injury. Methylprednisolone has been shown to be beneficial in attenuating the effects of warm ischemia-reperfusion injury in liver. The purpose of this study was to look at the role of methylprednisolone on warm ischemia-reperfusion injury in the presence of cholestasis. METHODS: Male Sprague-Dawley rats were divided into 3 groups. A reversible cholestatic model was created in 13 rats using a polyethylene tube, and a sham laparotomy was done in 6 rats. After 7 days, rats were subjected to 30 minutes of 70% hepatic ischemia followed by reperfusion. Cholestasis was reversed by draining the tube into the duodenum. Two hours prior to ischemia, 7 cholestatic rats received 30 mg/kg of methylprednisolone IV. Rats were euthanized 24 hours post-IR injury, when liver and blood samples were obtained.
CONCLUSIONS: Our results demonstrate that postoperative inflammation of the tunica muscularis can be reduced by the macrophage-specific c-Raf-kinase inhibitor CPSI-2364. This inhibition prevents development of POI in swine. Therefore, CPSI-2364 is a potent perioperative drug for the prophylaxis of postoperative intestinal dysmotility following abdominal surgery.
RESULTS: Methylprednisolone had a protective effect on the IR injury in the presence of cholestasis, with a significant decrease in AST (P ⬍ 0.01) and interleukin-6 levels (P ⫽ 0.04). On histological examination of the liver, steroids attenuated the IR injury changes with a significant difference noted in architectural distortion (P ⫽ 0.01), cytoplasmic vacuolation (P ⫽ 0.01), and hepatocyte dropout zones (P ⫽ 0.04).
Continuity of care: Readmission to the same hospital following gastric cancer resection Joan J Ryoo MD, Hiroko Kunitake MD, Stanley K Frencher Jr MD, MPH, Sierra R Matula MD, Melinda M Gibbons MD, MSHS, David S Zingmond MD, PhD, Clifford Y Ko MD, MS, MSHS, FACS UCLA Robert Wood Johnson Clinical Scholars Program, Los Angeles, CA
CONCLUSIONS: Methylprednisolone attenuated the postischemic and inflammatory response in the presence of cholestasis. Methylprednisolone may be considered as a pharmacological preconditioning and protective agent against IR injury in the presence of cholestasis.
INTRODUCTION: While continuity of care has been established as beneficial in the outpatient setting, its importance in the surgical inpatient context is less certain. We examined same-hospital readmission and its impact on mortality among surgically treated gastric cancer patients.
Preoperative application of CPSI-2364 per os attenuates inflammatory reactions in the tunica muscularis and prevents postoperative ileus in swine
METHODS: Operatively managed gastric cancer cases from 1994 to 2004 were identified through the California Cancer Registry linked to the state inpatient file (OSHPD), with follow-up through 2006. We identified predictors of readmission to the same (vs different) hospital within 90 days of discharge from index hospitalization and death within 1 year of surgery by using multivariate logistic and probit regressions, respectively. Data were analyzed using Stata Version 9.2 (College Station, TX).
Tim O Vilz MD, Nils Sommer, Sven Wehner PhD, Andreas Hirner MD, Joerg C Kalff MD, FACS Department of Surgery, University of Bonn, Bonn, North RhineWestphalia, Germany INTRODUCTION: The mechanical trauma of the gut is an unavoidable consequence of abdominal surgery leading to postoperative ileus (POI). Former studies revealed the activation of the resident macrophages in the tunica muscularis as an initial step in the inflammatory cascade. The aim of this study was to investigate the efficacy of the macrophage-specific c-Raf-kinase inhibitor CPSI-2364 in preventing POI in swine.
RESULTS: Of 10,372 surgically treated gastric cancer cases, 3,172 were readmitted within 90 days (2,335 to the same hospital). Controlling for age, sex, insurance status, cancer stage, and comorbidities, the odds ratio (95% confidence interval [CI]) of significant predictors of same hospital readmission included the following: total (vs partial) gastrectomy, 1.42 (1.23–1.63); discharge to home (vs not home), 1.56 (1.37–1.78); and treatment at a Commission on Cancer hospital, 1.33 (1.20–1.48). Readmission to the same hospital con-
METHODS: Swine were treated orally with placebo or CPSI-2364 before intestinal manipulation or sham operation. In addition to
© 2009 by the American College of Surgeons Published by Elsevier Inc.
ISSN 1072-7515/09/$34.00
S16
Protective effect of methylprednisolone on warm ischemia-reperfusion injury in a cholestatic rat liver Gokulakkrishna Subhas MD, MRCS, Aditya Gupta MD, Daniel Bakston MD, Boris Silberberg MD, Catherine Lobocki MS, MT, Lee Andrus LVT, LAT, BIS, Melissa Decker LVT, LAT, Vijay K Mittal MD, FACS, Michael J Jacobs MD, FACS Providence Hospital and Medical Centers, Southfield, MI
RESULTS: In CPSI-2364–treated swine, myeloperoxidase activity was significantly reduced compared with the placebo group (placebo, 254.2 ⫾ 87.7; CPSI-2364, 102,9 ⫾ 38.3 U/mg tissue). In addition, the onset of defecation was earlier after CPSI-2364 treatment. Functional studies showed an improved contractility of jejunal muscularis strips (placebo, 0.98 ⫾ 0.62; CPSI-2364, 1.91 ⫾ 1.29 g/mm2/s) and an accelerated gastrointestinal transit time in the CPSI-2364 group (geometric center: placebo, 7.67 ⫾ 4.26; CPSI2364, 13 ⫾ 0.66). Laboratory parameters and clinical examination showed no signs of organ disturbances after drug treatment.
INTRODUCTION: Cholestasis is associated with an increased risk of postoperative morbidity and mortality in patients who undergo liver surgery. Cholestasis has been identified as a risk factor for oxidative stress, and it potentially enhances postischemic-reperfusion (IR) injury. Methylprednisolone has been shown to be beneficial in attenuating the effects of warm ischemia-reperfusion injury in liver. The purpose of this study was to look at the role of methylprednisolone on warm ischemia-reperfusion injury in the presence of cholestasis. METHODS: Male Sprague-Dawley rats were divided into 3 groups. A reversible cholestatic model was created in 13 rats using a polyethylene tube, and a sham laparotomy was done in 6 rats. After 7 days, rats were subjected to 30 minutes of 70% hepatic ischemia followed by reperfusion. Cholestasis was reversed by draining the tube into the duodenum. Two hours prior to ischemia, 7 cholestatic rats received 30 mg/kg of methylprednisolone IV. Rats were euthanized 24 hours post-IR injury, when liver and blood samples were obtained.
CONCLUSIONS: Our results demonstrate that postoperative inflammation of the tunica muscularis can be reduced by the macrophage-specific c-Raf-kinase inhibitor CPSI-2364. This inhibition prevents development of POI in swine. Therefore, CPSI-2364 is a potent perioperative drug for the prophylaxis of postoperative intestinal dysmotility following abdominal surgery.
RESULTS: Methylprednisolone had a protective effect on the IR injury in the presence of cholestasis, with a significant decrease in AST (P ⬍ 0.01) and interleukin-6 levels (P ⫽ 0.04). On histological examination of the liver, steroids attenuated the IR injury changes with a significant difference noted in architectural distortion (P ⫽ 0.01), cytoplasmic vacuolation (P ⫽ 0.01), and hepatocyte dropout zones (P ⫽ 0.04).
Continuity of care: Readmission to the same hospital following gastric cancer resection Joan J Ryoo MD, Hiroko Kunitake MD, Stanley K Frencher Jr MD, MPH, Sierra R Matula MD, Melinda M Gibbons MD, MSHS, David S Zingmond MD, PhD, Clifford Y Ko MD, MS, MSHS, FACS UCLA Robert Wood Johnson Clinical Scholars Program, Los Angeles, CA
CONCLUSIONS: Methylprednisolone attenuated the postischemic and inflammatory response in the presence of cholestasis. Methylprednisolone may be considered as a pharmacological preconditioning and protective agent against IR injury in the presence of cholestasis.
INTRODUCTION: While continuity of care has been established as beneficial in the outpatient setting, its importance in the surgical inpatient context is less certain. We examined same-hospital readmission and its impact on mortality among surgically treated gastric cancer patients.
Preoperative application of CPSI-2364 per os attenuates inflammatory reactions in the tunica muscularis and prevents postoperative ileus in swine
METHODS: Operatively managed gastric cancer cases from 1994 to 2004 were identified through the California Cancer Registry linked to the state inpatient file (OSHPD), with follow-up through 2006. We identified predictors of readmission to the same (vs different) hospital within 90 days of discharge from index hospitalization and death within 1 year of surgery by using multivariate logistic and probit regressions, respectively. Data were analyzed using Stata Version 9.2 (College Station, TX).
Tim O Vilz MD, Nils Sommer, Sven Wehner PhD, Andreas Hirner MD, Joerg C Kalff MD, FACS Department of Surgery, University of Bonn, Bonn, North RhineWestphalia, Germany INTRODUCTION: The mechanical trauma of the gut is an unavoidable consequence of abdominal surgery leading to postoperative ileus (POI). Former studies revealed the activation of the resident macrophages in the tunica muscularis as an initial step in the inflammatory cascade. The aim of this study was to investigate the efficacy of the macrophage-specific c-Raf-kinase inhibitor CPSI-2364 in preventing POI in swine.
RESULTS: Of 10,372 surgically treated gastric cancer cases, 3,172 were readmitted within 90 days (2,335 to the same hospital). Controlling for age, sex, insurance status, cancer stage, and comorbidities, the odds ratio (95% confidence interval [CI]) of significant predictors of same hospital readmission included the following: total (vs partial) gastrectomy, 1.42 (1.23–1.63); discharge to home (vs not home), 1.56 (1.37–1.78); and treatment at a Commission on Cancer hospital, 1.33 (1.20–1.48). Readmission to the same hospital con-
METHODS: Swine were treated orally with placebo or CPSI-2364 before intestinal manipulation or sham operation. In addition to
© 2009 by the American College of Surgeons Published by Elsevier Inc.
ISSN 1072-7515/09/$34.00
S16