73 results on '"Cary B. Aarons"'
Search Results
52. Open adhesiolysis is more effective in reducing adhesion reformation than laparoscopic adhesiolysis in an experimental model
- Author
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R. Matteotti, James M. Becker, Scott G. Prushik, Cary B. Aarons, Karen L. Reed, Arthur F. Stucchi, and Adam C. Gower
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Male ,Insufflation ,medicine.medical_specialty ,Necrosis ,medicine.medical_treatment ,Adhesion (medicine) ,Tissue Adhesions ,Tissue plasminogen activator ,Transforming Growth Factor beta1 ,chemistry.chemical_compound ,Laparotomy ,Plasminogen Activator Inhibitor 1 ,Secondary Prevention ,medicine ,Animals ,RNA, Messenger ,Rats, Wistar ,Tumor Necrosis Factor-alpha ,business.industry ,Peritoneal Fibrosis ,Carbon Dioxide ,medicine.disease ,Rats ,Surgery ,chemistry ,Tissue Plasminogen Activator ,Plasminogen activator inhibitor-1 ,Laparoscopy ,medicine.symptom ,business ,Plasminogen activator ,Fibrinolytic agent ,medicine.drug - Abstract
Background This study compared adhesion reformation after open and laparoscopic adhesiolysis in a rat model. Methods Adhesions were induced by surgically creating ischaemic buttons on the peritoneal side wall. After 7 days the animals underwent laparoscopy with carbon dioxide insufflation or laparotomy to score and lyse adhesions. Peritoneal tissue and fluid were collected after 24 h in a subset of animals, and adhesion reformation was scored 7 days after lysis in the remainder. Tissue plasminogen activator (tPA), plasminogen activator inhibitor (PAI) 1, transforming growth factor (TGF) β1 and tumour necrosis factor (TNF) α mRNA, and total fibrinolytic activity were assessed. The abdomen of non-operated animals was insufflated for 7, 15 or 30 min with carbon dioxide, after which tPA and PAI-1 mRNA and total fibrinolytic activity were measured. Results Animals that underwent open adhesiolysis had 60 per cent fewer reformed adhesions than the laparoscopic adhesiolysis group (P < 0·001). There were no differences in tPA activity or tPA, PAI-1 and TNF-α mRNA between groups, but TGF-β1 mRNA levels were significantly increased in the open group. Carbon dioxide insufflation did not affect peritoneal tPA activity. Conclusion Open adhesiolysis may be more beneficial in minimizing adhesion reformation in the management of adhesion-related complications.
- Published
- 2010
53. Intraperitoneal Administration of Methylene Blue Attenuates Oxidative Stress, Increases Peritoneal Fibrinolysis, and Inhibits Intraabdominal Adhesion Formation
- Author
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Stanley Heydrick, James M. Becker, Cary B. Aarons, Arthur F. Stucchi, Karen L. Reed, Adam C. Gower, and Philip A. Cohen
- Subjects
Male ,medicine.medical_treatment ,Adhesion (medicine) ,Tissue Adhesions ,Pharmacology ,Dinoprost ,medicine.disease_cause ,Thiobarbituric Acid Reactive Substances ,Antioxidants ,chemistry.chemical_compound ,Peritoneum ,Abdomen ,Fibrinolysis ,medicine ,Animals ,Ascitic Fluid ,Enzyme Inhibitors ,Rats, Wistar ,Peroxidase ,biology ,T-plasminogen activator ,NADPH Oxidases ,medicine.disease ,Rats ,Methylene Blue ,Oxidative Stress ,medicine.anatomical_structure ,chemistry ,Biochemistry ,NAD(P)H oxidase ,Myeloperoxidase ,biology.protein ,Surgery ,Reactive Oxygen Species ,Injections, Intraperitoneal ,Methylene blue ,Oxidative stress - Abstract
Mounting evidence indicates that postoperative oxidative stress may be linked to decreased fibrinolytic activity and, subsequently, the development of intraabdominal adhesions. The goal of this study was to determine if methylene blue, a highly redox active dye that has been shown to inhibit adhesion formation (1) acts as an antioxidant in the postoperative peritoneum, and (2) subsequently affects fibrinolytic activity.Intraabdominal adhesions were surgically induced in rats receiving methylene blue (30 mg/kg) or vehicle (sterile water) intraperitoneally at surgery. At 24 h and 7 d following surgery, adhesion formation, oxidative stress, and peritoneal fibrinolytic activity were assessed.Methylene blue did not affect adhesion formation at 24 h, but did induce a50% regression in adhesions after 7 d (P0.05). Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and myeloperoxidase (MPO) activities, and 8-isoprostane and thiobarbituric acid-reactive substances were all significantly increased in peritoneal tissue samples (P0.05) by 24 h following surgery. Methylene blue inhibited NADPH oxidase by 98% and MPO activity by 78% in the 24 h tissue samples, and blunted the corresponding surgery-induced increases in tissue lipid and protein oxidation. Furthermore, methylene blue significantly increased (P0.05) fibrinolytic activity in peritoneal fluid at 24 h.Methylene blue acts as an antioxidant in this experimental system and may reduce intraabdominal adhesion formation by enhancing peritoneal fibrinolytic activity following surgery.
- Published
- 2007
54. Successful Sphincter-Sparing Surgery for All Anal Fistulas
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Cary B. Aarons, Kelly M. Tyler, and Stephen M. Sentovich
- Subjects
Adult ,Male ,Anal fistula ,medicine.medical_specialty ,Fistula ,Rectum ,Fibrin Tissue Adhesive ,Fistulotomy ,Surgical Flaps ,medicine ,Humans ,Rectal Fistula ,Fibrin glue ,Digestive System Surgical Procedures ,Aged ,Retrospective Studies ,business.industry ,General surgery ,Suture Techniques ,Gastroenterology ,Retrospective cohort study ,General Medicine ,Middle Aged ,medicine.disease ,Colorectal surgery ,Surgery ,Treatment Outcome ,medicine.anatomical_structure ,Sphincter ,Female ,Tissue Adhesives ,business ,Algorithms ,Follow-Up Studies - Abstract
This study was designed to evaluate the success of a sphincter-sparing treatment algorithm for patients with anal fistulas. All patients with anal fistulas presenting to a single surgeon from 1999 to 2004 were retrospectively reviewed. Patients were treated according to a sphincter-sparing algorithm that utilized three operative approaches: subcutaneous fistulotomy, seton placement followed by fibrin glue, and/or seton placement followed by rectal advancement flap. Data analyzed included: age, gender, type of fistula, operative intervention, treatment success, and functional results. A total of 137 patients with anal fistulas were evaluated (age range, 23–74 years). Fistula etiology was cryptoglandular in 116 (85 percent), inflammatory bowel disease in 9 (7 percent), HIV in 3 (2 percent), and miscellaneous in 9 (7 percent). A subcutaneous fistulotomy was possible in 38 patients (28 percent), and all of these patients healed. The remaining 99 patients (72 percent) with transsphincteric fistulas underwent staged procedures: 89 patients (65 percent) underwent seton placement followed by fibrin glue closure (55 healed, 62 percent success rate), 9 patients had seton placement followed by flap (9 healed, 100 percent success rate), and 1 patient had seton placement alone. Of the 34 patients with fibrin glue failure, retreatment with glue was successful in 8 of 14 (57 percent success rate). The remaining 20 patients who declined glue retreatment and the 6 patients who failed glue retreatment underwent flap (26 healed, 100 percent success rate). All fistulas healed with an average of two operations per patient, and fecal continence was maintained in all patients. By using staged operative procedures without any division of anal sphincter muscle, all fistulas healed with excellent functional results. A sphincter-sparing approach can successfully treat all anal fistulas.
- Published
- 2007
55. A neurokinin 1 receptor antagonist decreases adhesion reformation after laparoscopic lysis of adhesions in a rat model of adhesion formation
- Author
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Arthur F. Stucchi, R. Matteotti, James M. Becker, Scott G. Prushik, Cary B. Aarons, Karen L. Reed, Adam C. Gower, and Susan E. Leeman
- Subjects
Male ,medicine.medical_specialty ,medicine.medical_treatment ,Ischemia ,Adhesion (medicine) ,Tissue Adhesions ,Tissue plasminogen activator ,Andrology ,Neurokinin-1 Receptor Antagonists ,Peritoneum ,Recurrence ,Tachykinin receptor 1 ,medicine ,Animals ,Rats, Wistar ,Saline ,business.industry ,Antagonist ,Bridged Bicyclo Compounds, Heterocyclic ,medicine.disease ,Rats ,Surgery ,Disease Models, Animal ,medicine.anatomical_structure ,Laparoscopy ,business ,Abdominal surgery ,medicine.drug - Abstract
Up to 94% of patients experience fibrous adhesions after abdominal surgery, and a significant number of these patients require a second operation for open or laparoscopic lysis of adhesions (LOA). The authors have previously shown that inhibition of the binding of tachykinin ligands to the neurokinin 1 receptor (NK-1R) using the neurokinin 1 receptor antagonist (NK-1RA) CJ-12,255 decreases primary adhesion formation and upregulates the peritoneal fibrinolytic system in a rat model. Whereas most studies have focused on the prevention of primary adhesions, few have addressed adhesion reformation after LOA. This study aimed to determine the effects of NK-1RA administration on adhesion reformation and peritoneal fibrinolytic activity after laparoscopic LOA. Adhesions were induced in 31 rats using our previously described ischemic button model. The rats underwent laparoscopy 7 days later, during which adhesions were scored and lysed followed by administration of the NK-1RA or saline. Then 7 days after LOA, 23 rats were killed and adhesions were scored. Eight rats also were killed 24 h after the LOA to obtain peritoneal tissue and fluid, which were analyzed for tissue plasminogen activator (tPA) mRNA expression and peritoneal fibrinolytic activity by reverse transcriptase-polymerase chain reaction (RT-PCR) and bioassay, respectively. At laparoscopy, 79% ± 3% of the buttons formed adhesions. In the saline-administered control animals, 42% ± 3.2% of the buttons reformed adhesions after LOA (p
- Published
- 2007
56. Mortality Associated with Medical Therapy Versus Elective Colectomy in Ulcerative Colitis
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Mark T. Osterman, Fenglong Xie, Jeffrey R. Curtis, Meenakshi Bewtra, Kimberly A. Forde, Qufei Wu, Jason A. Roy, Cary B. Aarons, James D. Lewis, Lang Chen, and Craig Newcomb
- Subjects
Adult ,Male ,medicine.medical_specialty ,Adolescent ,medicine.medical_treatment ,Medicare ,Inflammatory bowel disease ,Article ,Young Adult ,Adrenal Cortex Hormones ,Internal Medicine ,medicine ,Humans ,Colitis ,health care economics and organizations ,Colectomy ,Aged ,Proportional Hazards Models ,Retrospective Studies ,Aged, 80 and over ,Medicaid ,business.industry ,General surgery ,Mortality rate ,Age Factors ,Retrospective cohort study ,General Medicine ,Middle Aged ,medicine.disease ,Survival Analysis ,Ulcerative colitis ,United States ,Elective Surgical Procedures ,Colitis, Ulcerative ,Female ,Elective Surgical Procedure ,business ,Immunosuppressive Agents ,Cohort study - Abstract
Ulcerative colitis (UC) can be treated with surgery or medications. Patients often must choose between long-term immunosuppressant therapy or total colectomy. Whether one of these treatment approaches has a mortality benefit is uncertain.To determine whether patients with advanced UC treated with elective colectomy have improved survival compared with those treated with medical therapy.Retrospective matched cohort study.Data from all 50 states for Medicaid beneficiaries (2000 to 2005), Medicare beneficiaries (2006 to 2011), and dual-eligible persons (2000 to 2011).830 patients with UC pursuing elective colectomy and 7541 matched patients with UC pursuing medical therapy.The primary outcome was time to death. Cox proportional hazards models were used to compare the survival of patients with advanced UC treated with elective colectomy or medical therapy. The models controlled for significant comorbid conditions through matched and adjusted analysis.The mortality rates associated with elective surgery and medical therapy were 34 and 54 deaths per 1000 person-years, respectively. Elective colectomy was associated with improved survival compared with long-term medical therapy (adjusted hazard ratio [HR], 0.67 [95% CI, 0.52 to 0.87]), although this result did not remain statistically significant in all sensitivity analyses. Post hoc analysis by age group showed improved survival with surgery in patients aged 50 years or older with advanced UC (HR, 0.60 [CI, 0.45 to 0.79]; P = 0.032 for age-by-treatment interaction).Retrospective nonrandomized analysis is subject to residual confounding. The source cohort was derived from different databases throughout the study. Sensitivity and secondary analyses had reduced statistical power.Elective colectomy seemed to be associated with improved survival relative to medical therapy among patients aged 50 years or older with advanced UC.National Institutes of Health and Agency for Healthcare Research and Quality.
- Published
- 2015
57. Surgical Approaches to Cancer in Patients Who Have Inflammatory Bowel Disease
- Author
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Cary B. Aarons, James M. Becker, and Arthur F. Stucchi
- Subjects
medicine.medical_specialty ,Colorectal cancer ,medicine.medical_treatment ,Disease ,Malignancy ,Inflammatory bowel disease ,Gastroenterology ,Perioperative Care ,Primary sclerosing cholangitis ,Postoperative Complications ,Internal medicine ,medicine ,Humans ,Digestive System Surgical Procedures ,Clinical Trials as Topic ,business.industry ,Cancer ,Inflammatory Bowel Diseases ,medicine.disease ,Ulcerative colitis ,digestive system diseases ,Treatment Outcome ,Colonic Neoplasms ,Lymphadenectomy ,business ,Precancerous Conditions - Abstract
IBD clearly increases the risk for GI malignancies, especially CRC. The absolute number of patients that develops such malignancies is low compared with the overall cancer rate; however, younger age of onset, higher relative risk, unique clinical presentations, and problems with early diagnosis make this a serious complication of IBD. With the exception of patients with comorbid complications, such as primary sclerosing cholangitis, the prognosis is no worse for CRCs that arise as the result of IBD compared with those that arise sporadically. The prognosis remains poor for small bowel adenocarcinomas in patients who have CD, primarily because of their advanced stage at detection. Diligent surveillance is essential for early detection and treatment of IBD-related CRCs in patients with unresected colons, long-standing or extensive disease, and in those who have early-onset CD, although pundits still question whether it significantly affects prognosis and survival. Better surveillance techniques for small bowel dysplasia or malignancy in patients who have CD is needed, especially given the poor prognosis of these patients when advanced cancers are detected. Depending on the presentation and disease diagnosis, patients have several surgical treatment options and can expect good outcomes for all. When the appropriate surgical technique is used in patients who have colon or rectal cancer, along with adjuvant chemotherapy when appropriate, prognosis and function is good; however, the experience of the surgeon can affect the prognosis for IBD-related GI cancers. Surgical therapy is based not only on general oncologic principles, but also on the surgery that is appropriate for the IBD diagnosis. Resection of the mesentery and lymphadenectomy should be performed according to oncologic principles. Postoperative survival for IBD-related CRC is good, and diligent surveillance and follow-up are critical to the patient's overall prognosis.
- Published
- 2006
58. Management of malignant colon polyps: Current status and controversies
- Author
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Cary B. Aarons, Skandan Shanmugan, and Joshua I. S. Bleier
- Subjects
Pathology ,medicine.medical_specialty ,Colorectal cancer ,Colonoscopy ,Colonic Polyps ,Endoscopic mucosal resection ,Adenocarcinoma ,Risk Assessment ,Risk Factors ,medicine ,Carcinoma ,Humans ,Neoplasm Invasiveness ,Colectomy ,medicine.diagnostic_test ,business.industry ,Patient Selection ,Gastroenterology ,Cancer ,Minireviews ,General Medicine ,medicine.disease ,digestive system diseases ,Colon polyps ,Treatment Outcome ,Dysplasia ,Lymphatic Metastasis ,Colonic Neoplasms ,business - Abstract
Colon cancer remains a significant clinical problem worldwide and in the United States it is the third most common cancer diagnosed in men and women. It is generally accepted that most malignant neoplasms of the colon arise from precursor adenomatous polyps. This stepwise progression of normal epithelium to carcinoma, often with intervening dysplasia, occurs as a result of multiple sequential, genetic mutations-some are inherited while others are acquired. Malignant polyps are defined by the presence of cancer cells invading through the muscularis mucosa into the underlying submucosa (T1). They can appear benign endoscopically but the presence of malignant invasion histologically poses a difficult and often controversial clinical scenario. Emphasis should be initially focused on the endoscopic assessment of these lesions. Suitable polyps should be resected en-bloc, if possible, to facilitate thorough evaluation by pathology. In these cases, proper attention must be given to the risks of residual cancer in the bowel wall or in the surrounding lymph nodes. If resection is not feasible endoscopically, then these patients should be referred for surgical resection. This review will discuss the important prognostic features of malignant polyps that will most profoundly affect this risk profile. Additionally, we will discuss effective strategies for their overall management.
- Published
- 2014
59. Perioperative fluid restriction
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Cary B. Aarons and Joshua I. S. Bleier
- Subjects
medicine.medical_specialty ,Fluid administration ,business.industry ,Gastroenterology ,Fluid management ,Perioperative ,Enteral administration ,Article ,Surgery ,Regimen ,medicine ,Bowel preparation ,Fluid restriction ,business ,Surgical patients - Abstract
Perioperative fluid management of the colorectal surgical patient has evolved significantly over the last five decades. Older notions espousing aggressive hydration have been shown to be associated with increased complications. Newer data regarding fluid restriction has shown an association with improved outcomes. Management of perioperative fluid administration can be considered in three primary phases: In the preoperative phase, data suggests that avoidance of preoperative bowel preparation and avoidance of undue preoperative dehydration can improve outcomes. Although the type of intraoperative fluid given does not have a significant effect on outcome, data do suggest that a restrictive fluid regimen results in improved outcomes. Finally, in the postoperative phase of fluid management, a fluid-restrictive regimen, coupled with early enteral feeding also seems to result in improved outcomes.
- Published
- 2014
60. Current surgical considerations for colorectal cancer
- Author
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Cary B, Aarons and Najjia N, Mahmoud
- Published
- 2013
61. Iatrogenic Kaposi Sarcoma in an HIV-Negative Young Man With Crohn Disease and IgA Nephropathy: A Case Report and Review of the Literature
- Author
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Qiuping Ma, Cary B. Aarons, Annika L. Windon, and Stuti Shroff
- Subjects
Crohn's disease ,Pathology ,medicine.medical_specialty ,Crohn disease ,business.industry ,Iatrogenic Kaposi Sarcoma ,Human immunodeficiency virus (HIV) ,virus diseases ,General Medicine ,medicine.disease ,medicine.disease_cause ,Nephropathy ,Immunology ,medicine ,Vascular tumor ,Sarcoma ,business ,Human herpesvirus - Abstract
Kaposi sarcoma (KS) is a vascular tumor associated with human herpesvirus 8 (HHV8) infections. The iatrogenic variant of KS frequently occurs in human immunodeficiency virus (HIV)-negative patients receiving prolonged immunosuppressive therapy. Isolated intestinal KS in the background of Crohn disease (CD) is exceeding rare, with only 2 reported cases in the literature since 1966. Here we report a case …
- Published
- 2015
62. Biliary Dyskinesia: Functional Gallbladder and Sphincter of Oddi Disorders
- Author
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Cary B. Aarons, Arthur F. Stucchi, and James M. Becker
- Subjects
medicine.medical_specialty ,medicine.anatomical_structure ,business.industry ,General surgery ,Gallbladder ,Internal medicine ,Sphincter of Oddi ,medicine ,Biliary dyskinesia ,business ,medicine.disease ,Gastroenterology - Published
- 2009
63. Lymph Node Retrieval and Assessment after Colorectal Cancer Resection: Are Pathologists Doing an Adequate Job?
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Stephen M. Sentovich, Cary B. Aarons, and Wayne W. LaMorte
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medicine.medical_specialty ,business.industry ,Colorectal cancer ,General surgery ,Public health ,Gastroenterology ,General Medicine ,medicine.disease ,Colorectal surgery ,Cancer resection ,Resection ,medicine.anatomical_structure ,Surgical oncology ,Medicine ,business ,Lymph node - Published
- 2008
64. A neurokinin-1 receptor antagonist that reduces intra-abdominal adhesion formation decreases oxidative stress in the peritoneum
- Author
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Adam C. Gower, Scott G. Prushik, James M. Becker, Stanley Heydrick, Karen L. Reed, Cary B. Aarons, and Arthur F. Stucchi
- Subjects
Male ,medicine.medical_specialty ,Isoprostane ,Time Factors ,Physiology ,Vascular Cell Adhesion Molecule-1 ,Tissue Adhesions ,Substance P ,medicine.disease_cause ,Dinoprost ,Peritoneal Diseases ,Antioxidants ,Protein Carbonylation ,chemistry.chemical_compound ,Gastrointestinal Agents ,Neurokinin-1 Receptor Antagonists ,Physiology (medical) ,Internal medicine ,Tachykinin receptor 1 ,medicine ,Animals ,RNA, Messenger ,Rats, Wistar ,Peroxidase ,Laparotomy ,NADPH oxidase ,Hepatology ,biology ,Chemistry ,Peritoneal fluid ,Gastroenterology ,Antagonist ,NADPH Oxidases ,Receptors, Neurokinin-1 ,Bridged Bicyclo Compounds, Heterocyclic ,Intercellular Adhesion Molecule-1 ,Rats ,Disease Models, Animal ,Oxidative Stress ,Endocrinology ,Neutrophil Infiltration ,NAD(P)H oxidase ,Myeloperoxidase ,biology.protein ,Peritoneum ,Reactive Oxygen Species ,Oxidative stress - Abstract
Oxidative stress has been implicated in intra-abdominal adhesion formation. Substance P, a neurokinin-1 receptor (NK-1R) ligand, facilitates leukocyte recruitment and reactive oxygen species (ROS) generation. We have shown in a rat model of adhesion formation that intraperitoneal administration of a NK-1R antagonist at the time of abdominal operation reduces postoperative adhesion formation. Thus we determined the effects of NK-1R antagonist administration on peritoneal leukocyte recruitment and oxidative stress within 24 h of surgery. Adhesions were induced in Wistar rats randomly assigned to receive the antagonist or vehicle intraperitoneally. Peritoneal tissue was isolated at 2, 4, 6, and 24 h after surgery for analysis of the oxidative stress biomarkers 8-isoprostane (8-IP), protein carbonyl, NADPH oxidase, myeloperoxidase (MPO), and ICAM-1 and VCAM-1 mRNAs. Total antioxidant capacity of peritoneal fluid was also determined. MPO, NADPH oxidase, 8-IP, and protein carbonyl were elevated ( P < 0.05) by 6 h. ICAM-1 mRNA was elevated ( P < 0.05) by 2 h, whereas VCAM-1 levels decreased ( P < 0.05) at 24 h. The NK-1R antagonist delayed the MPO rise and reduced ( P < 0.05) 8-IP levels by 6 h and ICAM-1 mRNA, VCAM-1 mRNA, and protein carbonyl at 2 h. The antagonist also increased ( P < 0.05) the antioxidant capacity of peritoneal fluid at all time points. These data further support a role for oxidative stress in adhesion formation and suggest that the NK-1R antagonist may limit adhesions, in part, by reducing postoperative oxidative stress through an inhibition of neutrophil recruitment and an increase in peritoneal fluid antioxidant capacity.
- Published
- 2007
65. Statins (HMG-CoA Reductase Inhibitors) Decrease Postoperative Adhesions by Increasing Peritoneal Fibrinolytic Activity
- Author
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Arthur F. Stucchi, Cary B. Aarons, Susan E. Leeman, Philip A. Cohen, Adam C. Gower, James M. Becker, and Karen L. Reed
- Subjects
Male ,Feature ,medicine.medical_specialty ,Atorvastatin ,medicine.medical_treatment ,Tissue Adhesions ,Tissue plasminogen activator ,Epithelium ,chemistry.chemical_compound ,Postoperative Complications ,In vivo ,Internal medicine ,Plasminogen Activator Inhibitor 1 ,Fibrinolysis ,medicine ,Animals ,Ascitic Fluid ,Humans ,Lovastatin ,RNA, Messenger ,Rats, Wistar ,Cells, Cultured ,Laparotomy ,biology ,business.industry ,Cholesterol ,Prognosis ,Rats ,Disease Models, Animal ,Endocrinology ,chemistry ,Tissue Plasminogen Activator ,HMG-CoA reductase ,biology.protein ,Surgery ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,Peritoneum ,business ,Plasminogen activator ,medicine.drug - Abstract
Objectives: The aims of this study were to determine if statins reduce adhesion formation in vivo and to identify the mechanism of action in vitro. Background: Intraperitoneal adhesions develop in up to 95% of patients following laparotomy. Adhesions are reduced by mechanisms that up-regulate fibrinolysis within the peritoneum. Statins promote fibrinolysis in the cardiovascular system and may play a role in the prevention of adhesions. Methods: Adhesions were induced in rats (n 102) using our previously described ischemic button model. Rats received vehicle (controls), lovastatin (30 mg/kg), or atorvastatin (30 mg/kg) as a single intraperitoneal dose at the time of laparotomy. Animals were killed and adhesions were quantified at day 7. Peritoneal fluid and tissue were collected at day 1 to measure tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) by real-time PCR and ELISA. To assess the effects of statins on wound healing, burst pressures were measured in anastomoses of the colon. The effects of lovastatin on tPA and PAI-1 production were measured in vitro in human mesothelial cells (HMC) in the presence or absence of mevalonate (MVA), geranylgeranyl-pyrophosphate (GGPP) and farnesylpyrophosphate (FPP), all intermediates in the cholesterol pathway downstream of HMG-CoA. The effect of a Rho protein inhibitor, exoenzyme C3 transferase, on tPA production was also determined. Results: Lovastatin and atorvastatin reduced adhesion formation by 26% and 58%, respectively (P 0.05), without affecting anastomotic burst pressure. At 24 hours, tPA mRNA levels in peritoneal tissue and tPA activity in peritoneal fluid from lovastatin-treated animals were increased by 57% and 379%, respectively (P 0.05), while PAI-1 levels were unchanged. HMC incubated with either lovastatin or atorvastatin showed concentration-dependent increases in tPA production and decreases in PAI-1 production (P 0.05). These lovastatin-induced changes in tPA and PAI-1 production were significantly reversed by the addition of MVA, GGPP, and FPP. The Rho protein inhibitor increased tPA production and rescued tPA production from the inhibitory effect of GGPP. Conclusion: These data suggest that statins administered within the peritoneum can up-regulate local fibrinolysis, while the in vitro studies show that this effect may be mediated, in part, by intermediates of the cholesterol biosynthetic pathway that regulate Rho protein signaling.
- Published
- 2007
66. Carcinoembryonic antigen-stimulated THP-1 macrophages activate endothelial cells and increase cell-cell adhesion of colorectal cancer cells
- Author
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Arthur F. Stucchi, Karen L. Reed, Charles W. Andrews, Cary B. Aarons, Stanley Heydrick, Peter Thomas, Kristen N. Bushell, James M. Becker, and Olga Bajenova
- Subjects
Cancer Research ,Pathology ,medicine.medical_specialty ,Cell ,Receptors, Cell Surface ,Cell Line ,Carcinoembryonic antigen ,Cell surface receptor ,medicine ,Cell Adhesion ,Macrophage ,Humans ,Cell adhesion ,biology ,Cell adhesion molecule ,business.industry ,Tumor Necrosis Factor-alpha ,Macrophages ,Endothelial Cells ,General Medicine ,Intercellular Adhesion Molecule-1 ,digestive system diseases ,Carcinoembryonic Antigen ,medicine.anatomical_structure ,Oncology ,Cell culture ,Cancer research ,biology.protein ,Tumor necrosis factor alpha ,business ,Colorectal Neoplasms ,E-Selectin - Abstract
The liver is the most common site for metastasis by colorectal cancer, and numerous studies have shown a relationship between serum carcinoembryonic antigen (CEA) levels and metastasis to this site. CEA activates hepatic macrophages or Kupffer cells via binding to the CEA receptor (CEA-R), which results in the production of cytokines and the up-regulation of endothelial adhesion molecules, both of which are implicated in hepatic metastasis. Since tissue macrophages implicated in the metastatic process can often be difficult to isolate, the aim of this study was to develop an in vitro model system to study the complex mechanisms of CEA-induced macrophage activation and metastasis. Undifferentiated, human monocytic THP-1 (U-THP) cells were differentiated (D-THP) to macrophages by exposure to 200 ng/ml phorbol myristate acetate (PMA) for 18 h. Immunohistochemistry showed two CEA-R isoforms present in both U- and D-THP cells. The receptors were localized primarily to the nucleus in U-THP cells, while a significant cell-surface presence was observed following PMA-differentiation. Incubation of D-THP-1 cells with CEA resulted in a significant increase in tumor necrosis factor-alpha (TNF-alpha) release over 24 h compared to untreated D-THP-1 or U-THP controls confirming the functionality of these cell surface receptors. U-THP cells were unresponsive to CEA. Attachment of HT-29 cells to human umbilical vein endothelial cells significantly increased at 1 h after incubation with both recombinant TNF-alpha and conditioned media from CEA stimulated D-THP cells by six and eightfold, respectively. This study establishes an in vitro system utilizing a human macrophage cell line expressing functional CEA-Rs to study activation and signaling mechanisms of CEA that facilitate tumor cell attachment to activated endothelial cells. Utilization of this in vitro system may lead to a more complete understanding of the expression and function of CEA-R and facilitate the design of anti-CEA-R therapeutic modalities that may significantly diminish the metastatic potential of CEA overexpressing colorectal tumors.
- Published
- 2006
67. The effectiveness of a single intraperitoneal infusion of a neurokinin-1 receptor antagonist in reducing postoperative adhesion formation is time dependent
- Author
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Susan E. Leeman, Arthur F. Stucchi, Adam C. Gower, Philip A. Cohen, Karen L. Reed, James M. Becker, and Cary B. Aarons
- Subjects
Male ,Colon ,Adhesion (medicine) ,Tissue Adhesions ,Tissue plasminogen activator ,chemistry.chemical_compound ,Postoperative Complications ,Neurokinin-1 Receptor Antagonists ,Colon surgery ,Abdomen ,medicine ,Animals ,Infusions, Parenteral ,Rats, Wistar ,Wound Healing ,business.industry ,Peritoneal fluid ,Anastomosis, Surgical ,Antagonist ,Receptors, Neurokinin-1 ,medicine.disease ,Bridged Bicyclo Compounds, Heterocyclic ,Rats ,chemistry ,Anesthesia ,Tissue Plasminogen Activator ,Surgery ,Neurokinin A ,business ,Wound healing ,Perfusion ,medicine.drug - Abstract
Current methods to prevent intraabdominal adhesions are not uniformly effective. We recently showed in rats that a neurokinin-1 receptor (NK-1R) antagonist is capable of reducing adhesion formation. To determine the clinical feasibility of using an NK-1R antagonist to reduce adhesions, this study examined the time dependence for the effectiveness of NK-1R antagonist administration and its effects on wound healing.Adhesions were surgically induced in rats receiving a single intraperitoneal infusion of the NK-1R antagonist, CJ-12,255, during or 1, 5, 12, or 24 hours after surgery. Adhesion formation was assessed 7 days later. In a subset of animals, tissue plasminogen activator (tPA) activity, which is a measure of peritoneal fibrinolytic activity, was determined in peritoneal fluid 24 hours after surgery (48 hours for animals infused at 24 hours). The tPA activity was also determined in nonoperated animals 24 hours after peritoneal injection of the NK-1R antagonist. Colonic burst pressures were measured 7 days after creation of anastomoses in rats that were administered the antagonist at surgery.The NK-1R antagonist significantly reduced (P=.003) intraabdominal adhesions when administered during or 1 hour after surgery, only moderately reduced (P=.08) adhesions when administered at 5 hours, and had no effect at 12 or 24 hours. Peritoneal tPA activity was significantly increased (P.05) in peritoneal fluid 24 hours after administration of the NK-1R antagonist regardless of the surgical procedure. The NK-1R antagonist did not alter colonic anastomotic healing.These data show that some of the events critical to adhesion formation occur within the first 5 hours following an abdominal operation in this model. The fact that the NK-1R antagonist does not impair colonic anastomotic healing enhances its usefulness as a therapeutic agent to inhibit adhesion formation.
- Published
- 2006
68. Methylene blue reduces intraabdominal adhesions by decreasing peritoneal oxidative stress and increasing peritoneal fibrinolytic activity
- Author
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Philip A. Cohen, James M. Becker, Karen L. Reed, Arthur F Stuchi, Adam C. Gower, Cary B. Aarons, and Stanley Heydrick
- Subjects
medicine.medical_specialty ,chemistry.chemical_compound ,Endocrinology ,Chemistry ,Internal medicine ,Genetics ,medicine ,medicine.disease_cause ,Molecular Biology ,Biochemistry ,Methylene blue ,Oxidative stress ,Biotechnology - Published
- 2006
69. A neurokinin‐1 receptor antagonist (NK‐1RA) that reduces postoperative adhesions decreases markers of oxidative stress in the peritoneum
- Author
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Karen L. Reed, Cary B. Aarons, Adam C. Gower, James M. Becker, Susan E. Leeman, Stanley Heydrick, and Arthur F. Stucchi
- Subjects
medicine.medical_specialty ,business.industry ,Antagonist ,medicine.disease_cause ,Biochemistry ,medicine.anatomical_structure ,Endocrinology ,Peritoneum ,Internal medicine ,Tachykinin receptor 1 ,Genetics ,medicine ,business ,Molecular Biology ,Oxidative stress ,Biotechnology - Published
- 2006
70. [Untitled]
- Author
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Scott G. Prushik, R. Matteotti, Adam C. Gower, James M. Becker, Cary B. Aarons, Karen L. Reed, and Arthur F. Stucchi
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Lysis ,business.industry ,Rat model ,Immunology ,Medicine ,Surgery ,Adhesion ,business ,Cell biology - Published
- 2007
71. A neurokinin 1 receptor antagonist (NK-1RA) decreases adhesion reformation after laparoscopic lysis of adhesions (LOA) in a rat model
- Author
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Scott G. Prushik, Adam C. Gower, Cary B. Aarons, Karen L. Reed, Ronald Matteotti, Arthur F. Stucchi, and James M. Becker
- Subjects
Lysis ,business.industry ,Rat model ,Tachykinin receptor 1 ,Immunology ,Antagonist ,Medicine ,Surgery ,Adhesion ,Pharmacology ,business - Published
- 2006
72. HMG-CoA reductase inhibitors (statins) decrease postoperative adhesions by increasing peritoneal fibrinolytic activity
- Author
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James M. Becker, Arthur F. Stucchi, Philip A. Cohen, Cary B. Aarons, Karen L. Reed, and Adam C. Gower
- Subjects
biology ,business.industry ,Peritoneal fluid ,medicine.medical_treatment ,Pharmacology ,Tissue plasminogen activator ,In vitro ,Laparotomy ,HMG-CoA reductase ,Fibrinolysis ,medicine ,biology.protein ,Surgery ,Lovastatin ,business ,Plasminogen activator ,medicine.drug - Abstract
METHODS: Adhesions were surgically induced in male Wistar rats (n 56) using an ischemic button model previously described. Rats received either vehicle (controls) or lovastatin (30mg/kg) as an intraperitoneal bolus dose at laparotomy. Animals were sacrificed after 1 or 7 days, adhesions were quantified, and peritoneal fluid and tissue were collected to measure tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1). The effects of statins on tPA and PAI-1 production were also measured in vitro in human mesothelial cells (HMC).
- Published
- 2005
73. Management of malignant colon polyps: current status and controversies.
- Author
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Aarons CB, Shanmugan S, and Bleier JI
- Subjects
- Adenocarcinoma classification, Adenocarcinoma secondary, Colectomy adverse effects, Colonic Neoplasms classification, Colonic Neoplasms pathology, Colonic Polyps classification, Colonic Polyps pathology, Colonoscopy adverse effects, Humans, Lymphatic Metastasis, Neoplasm Invasiveness, Patient Selection, Risk Assessment, Risk Factors, Treatment Outcome, Adenocarcinoma surgery, Colectomy methods, Colonic Neoplasms surgery, Colonic Polyps surgery, Colonoscopy methods
- Abstract
Colon cancer remains a significant clinical problem worldwide and in the United States it is the third most common cancer diagnosed in men and women. It is generally accepted that most malignant neoplasms of the colon arise from precursor adenomatous polyps. This stepwise progression of normal epithelium to carcinoma, often with intervening dysplasia, occurs as a result of multiple sequential, genetic mutations-some are inherited while others are acquired. Malignant polyps are defined by the presence of cancer cells invading through the muscularis mucosa into the underlying submucosa (T1). They can appear benign endoscopically but the presence of malignant invasion histologically poses a difficult and often controversial clinical scenario. Emphasis should be initially focused on the endoscopic assessment of these lesions. Suitable polyps should be resected en-bloc, if possible, to facilitate thorough evaluation by pathology. In these cases, proper attention must be given to the risks of residual cancer in the bowel wall or in the surrounding lymph nodes. If resection is not feasible endoscopically, then these patients should be referred for surgical resection. This review will discuss the important prognostic features of malignant polyps that will most profoundly affect this risk profile. Additionally, we will discuss effective strategies for their overall management.
- Published
- 2014
- Full Text
- View/download PDF
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