Demirali Onat

Effect of persistently elevated intraabdominal pressure on healing of colonic anastomoses

BACKGROUND The adverse effects of elevated intraabdominal pressure (IAP) on abdominal organs are realized, but its influence on anastomotic healing has not been studied. The aim of this study was to evaluate the effect of elevated IAP on healing of colonic anastomoses. METHODS Thirty rats, which all had right colonic anastomoses, were divided into five groups. Group 1 was the control group, and group 2 had fecal peritonitis. IAP was maintained between 4 to 6 mm Hg in group 3, 8 to 12 mm Hg in group 4, and 14 to 18 mm Hg in group 5 until all rats were sacrificed on day 4. Bursting pressures and tissue hydroxyproline concentrations of anastomoses were then analyzed and compared. RESULTS Mean +/- SEM of bursting pressures were 143+/-2.9 mm Hg in group 1, 72+/-14.4 mm Hg in group 2, 77.3+/-7.9 mm Hg in group 3, 57.5+/-11.2 mm Hg in group 4, and 40.1+/-9.6 mm Hg in group 5 (P<0.0001, one-way analysis of variance [ANOVA]). Mean +/- SEM of tissue hydroxyproline concentrations were 5.3+/-0.3 microg/mg in group 1, 4.7+/-0.5 microg/mg in group 2, 4.6+/-0.6 microg/mg in group 3, 3.6+/-0.5 microg/mg in group 4, and 2.4+/-0.2 microg/mg in group 5 (P = 0.0026, one-way ANOVA). The bursting pressure and hydroxyproline concentrations had good correlation (P<0.001, r = 0.76). CONCLUSIONS Elevated IAP delays healing of colonic anastomoses and 4 to 6 mm Hg IAP delays healing as much as fecal peritonitis. More elevated IAP delays healing more than fecal peritonitis. These events may be clinically important and may result from local-systemic effects of IAP.

Effects of Polyglycolic Acid and Polypropylene Meshes on Postoperative Adhesion Formation in Mice

Abstract The purpose of this study was to investigate the effects of polyglycolic acid (PGA), an absorbable (ABS) mesh, and polypropylene (PP), a nonabsorbable (NA) mesh, on intestinal adhesion formation. Altogether 72 mice were divided into a control group of 24, an ABS mesh group of 23, and an NA mesh group of 25. All three groups were divided into two subgroups for evaluation of adhesion severity at postoperative (po) days 5 and 90. Adhesion severity was measured with adhesion grading and tissue hydroxyproline (OHP) levels. Adhesion degree was minimal (1) in all subjects on day 5. Also there was no difference in tissue OHP levels between three groups on day 5 ( p > 0.05). Adhesion degree and tissue OHP levels as determinants of adhesion severity were higher in the PGA mesh group than the control group and the PP mesh group on day 90 (p < 0.001). There was no difference between the control group and the PP mesh groups (p > 0.05). Adhesion degree was higher on day 90 than on day 5 in the control group and the PGA mesh group (p < 0.05), whereas tissue OHP level was higher on day 90 than on day 5 in all three groups (p < 0.001). Also there was linear correlation between adhesion degree and tissue OHP levels (r= 0.86, p < 0.001). The study demonstrates that ABS PGA mesh has higher potential for adhesion formation than the NA PP mesh, probably related to the increased foreign body and inflammatory reactions during the absorption process of the mesh.

An experimental study of the effect of aprotinin on intestinal adhesion formation.

BACKGROUND Depression of fibrinolysis is known to be a major mechanism for postoperative adhesion formation. Because aprotinin inhibits fibrinolysis it may lead to an increase in adhesion formation whereas its anti-inflammatory effects may lead to a decrease in adhesion formation. Our aim is to clarify conflicting results in previous literature. METHODS Basal levels of intestinal hydroxyproline (OHP) content and local fibrinolytic activity (LFA) were determined using naive groups. In the experiment groups, adhesions were created by scraping and creating a transient ischemia of a segment of terminal ileum. Group I and II rats were injected subcutaneous (s.c.) normal saline (NS) for 3 days and single dose intraperitoneal (i.p.) NS, respectively. Group III and IV rats were injected s.c. aprotinin for 3 days and single dose i.p. aprotinin, respectively. Group V rats were injected intramuscular methylprednisolone (MP) for 3 days. LFA and OHP levels were determined on the second and fifth postoperative days. The severity of adhesion formation was graded on the fifth day. RESULTS Aprotinin decreased both the severity of adhesions and OHP levels whereas MP decreased only the severity of adhesions. There was an early depression of LFA at the second day in both NS and MP groups increasing to basal levels at the fifth day. OHP levels showed significant correlation with adhesion severity. CONCLUSION Results showed that aprotinin decreased intra-abdominal adhesion formation probably by preventing early depression of LFA.

Effects of Laparotomy, and Carbon Dioxide and Air Pneumoperitoneum, on Cellular Immunity and Peritoneal Host Defences in Rats

OBJECTIVE To assess the effects of laparotomy, and insufflation of carbon dioxide and air, on the immune system in rats. DESIGN Randomised laboratory study. SETTING Teaching hospital, Turkey. ANIMALS 77 Wistar rats randomly allocated to 2 groups one of which was sensitised with dinitrofluorobenzene (DNFB, n = 43) and one of which was not (n = 34). INTERVENTIONS The DNFB group was sensitised and subdivided into control (n = 8), laparotomy alone (n = 7), and insufflation with carbon dioxide (CO2) for 30 and 60 mins (n = 7 in each) or room air for 30 and 60 mins (n = 7 in each). A week later DNFB was reapplied to the ears. In the group not sensitised with DNFB the animals were subdivided similarly, the corresponding numbers in each group being, 6, 6, 6, 6, 5, and 5. MAIN OUTCOME MEASURES Delayed type hypersensitivity (DTH) measured by ear swelling in the DNFB group, and peritoneal bactericidal activity, total free peritoneal cell counts (TPC), and cell types in the non-sensitised group. RESULTS There were significant differences in the degree of ear swelling in the DNFB group between control and laparotomy groups (p = 0.0001) and between control and both insufflations of air (p = 0.002 and p = 0.0003, respectively). In the non-sensitised group peritoneal bactericidal activity was significantly increased after 7 hours in the 60 mins air insufflation group (p = 0.04). At 24 hours there were no differences among the groups. TPC were not affected. The number of peritoneal polymorphonuclear leucocytes (PMN) was significantly higher in the laparotomy alone group than in the control or any of the insufflation groups (p < 0.05). CONCLUSIONS Laparotomy and air insufflation depressed cell-mediated immunity. Peritoneal bactericidal activity was affected only after 60 minutes of air insufflation.

A Phase II Study on the Safety and Efficacy of 5-Fluorouracil, Epirubicin, Cyclophosphamide (FEC) Followed by Paclitaxel in the Adjuvant Treatment of Breast Cancer

The incorporation of a taxane into an anthracycline-containing regimen in the adjuvant treatment of breast cancer is a promising approach. In this study, we aimed to evaluate the safety and efficacy of four cycles of FEC (fluorouracil 500 mg/m2, epirubicin 70 mg/m2, cyclophosphamide 500 mg/m2, every 3 weeks) followed by four cycles of paclitaxel (175 mg/m2 every 3 weeks) in the adjuvant treatment of node-positive and other high-risk breast cancer patients. A total of 88 female patients were enrolled. Mean age (± SD) of the patients was 47 ± 10 (min: 24; max: 71). The patients were followed for a median of 48 months (min: 20; max: 64). The most common side effects were nausea-vomiting (grade I–II: 91%; grade III: 2%), as well as hematological toxicity (grade I–II: 70%; grade III: 3%). Although all patients experienced some degree of toxicity, it was severe enough to be classified as grade III or IV in only 10 (11%) of the cases. Of note, six (8%) patients had grade I and only one (1%) had grade II cardiotoxicity. No grade III or IV cardiotoxicity was observed. The full eight cycles of study treatment could be administered to 75 patients (85%). Side effects necessitated the reduction of the doses of FEC and paclitaxel in one (1%) and three patients (3%), respectively. Median overall (OS) and disease-free survival (DFS) have not yet been reached. Five-year OS and DFS have been estimated to be 78% and 61%, respectively. We conclude that FEC followed by paclitaxel is a well-tolerated and feasible regimen in the adjuvant treatment of early breast cancer. Its efficacity is comparable with other commonly used regimens and merits evaluation in a phase III study.

Pinealectomy Does Not Affect the Healing of Experimental Colonic Anastomoses

Gastrointestinal system anastomoses, especially colonic anastomoses, have significant morbidity and mortality despite recent technical improvements. Besides regulating the circadian rhythm, the pineal gland and its main neurohormone product melatonin have widespread actions in the organism. The purpose of this study was to investigate the effects of pinealectomy on the healing of colonic anastomoses. One hundred male albino Wistar rats were used in this study. The rats were separated into three groups: control, pinealectomy, and sham groups. In the control group, only colonic resection and anastomoses were performed. Following pinealectomy, colonic anastomosis was performed 2 weeks later on one half and 2 months later on the other half of the pinealectomy group. Only craniotomy was performed on the sham group, and the rats were separated and evaluated like the pinealectomy group. Colonic anastomoses were evaluated on postanastomotic day 3 and 7 by measuring the bursting pressure and the hydroxyproline levels in the anastomotic segments. There was no difference in the bursting pressure measurements between the groups on both postoperative day 3 and 7. Although hydroxyproline levels were different between groups on both postanastomotic days 3 and 7, it has been observed that neither normal nor anastomotic hydroxyproline levels influenced the anastomotic bursting pressure measurements. The percent deviation from the normal values was compared in the anastomotic segments, and no differences were found regarding the bursting pressure and hydroxyproline levels. It was concluded that pinealectomy has no effect on the healing of colonic anastomoses.