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Lambrou I, Mantzoros I, Ioannidis O, Tatsis D, Anestiadou E, Bisbinas V, Pramateftakis MG, Kotidis E, Driagka B, Kerasidou O, Symeonidis S, Bitsianis S, Sifaki F, Angelopoulos K, Demetriades H, Angelopoulos S. Effect of growth hormone on colonic anastomosis after intraperitoneal administration of 5-fluorouracil, bleomycin and cisplatin: An experimental study. World J Gastrointest Surg 2024; 16:2679-2688. [PMID: 39220091 PMCID: PMC11362934 DOI: 10.4240/wjgs.v16.i8.2679] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2024] [Revised: 05/20/2024] [Accepted: 06/17/2024] [Indexed: 08/16/2024] Open
Abstract
BACKGROUND Growth hormone (GH) plays a crucial role in wound healing and tissue repair in postoperative patients. In particular, colonic anastomosis healing following colorectal surgery is impaired by numerous chemotherapy agents. AIM To investigate whether GH can improve the healing of a colonic anastomosis following the adverse effects of intraperitoneal administration of 5-fluorouracil (5-FU), bleomycin and cisplatin. METHODS Eighty Wistar rats underwent laparotomy and a 1 cm-resection of the transverse colon, followed by an end-to-end anastomosis under general anesthesia. The rats were blindly allocated into four equal groups and administered a different daily intraperitoneal therapeutic regimen for 6 days. The control group (A) received normal saline. Group B received chemotherapy with 5-FU (20 mg/kg), bleomycin (4 mg/kg) and cisplatin (0.7 mg/kg). Group C received GH (2 mg/kg), and group D received the aforementioned combination chemotherapy and GH, as described. The rats were sacrificed on the 7th postoperative day and the anastomoses were macroscopically and microscopically examined. Body weight, bursting pressure, hydroxyproline levels and inflammation markers were measured. RESULTS All rats survived until the day of sacrifice, with no infections or other complications. A decrease in the body weight of group D rats was observed, not statistically significant compared to group A (P = 1), but significantly different to groups C (P = 0.001) and B (P < 0.01). Anastomotic dehiscence rate was not statistically different between the groups. Bursting pressure was not significantly different between groups A and D (P = 1.0), whereas group B had a significantly lower bursting pressure compared to group D (P < 0.001). All groups had significantly more adhesions than group A. Hydroxyproline, as a measurement of collagen deposition, was significantly higher in group D compared to group B (P < 0.05), and higher, but not statistically significant, compared to group A. Significant changes in group D were recorded, compared to group A regarding inflammation (3.450 vs 2.900, P = 0.016) and fibroblast activity (2.75 vs 3.25, P = 0.021). Neoangiogenesis and collagen deposition were not significantly different between groups A and D. Collagen deposition was significantly increased in group D compared to group B (P < 0.001). CONCLUSION Intraperitoneal administration of chemotherapy has an adverse effect on the healing process of colonic anastomosis. However, GH can inhibit the deleterious effect of administered chemotherapy agents and induce colonic healing in rats.
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Affiliation(s)
- Ioannis Lambrou
- Fourth Department of Surgery, Medical School, Aristotle University of Thessaloniki, Thessaloniki 57010, Greece
| | - Ioannis Mantzoros
- Fourth Department of Surgery, Medical School, Aristotle University of Thessaloniki, Thessaloniki 57010, Greece
| | - Orestis Ioannidis
- Fourth Department of Surgery, Medical School, Aristotle University of Thessaloniki, Thessaloniki 57010, Greece
| | - Dimitrios Tatsis
- Fourth Department of Surgery, Medical School, Aristotle University of Thessaloniki, Thessaloniki 57010, Greece
| | - Elissavet Anestiadou
- Fourth Department of Surgery, Medical School, Aristotle University of Thessaloniki, Thessaloniki 57010, Greece
| | - Vasiliki Bisbinas
- Department of ENT, Royal Cornwall Hospitals NHS Trust, Cornwall TR1 3LJ, United Kingdom
| | | | - Efstathios Kotidis
- Fourth Department of Surgery, Medical School, Aristotle University of Thessaloniki, Thessaloniki 57010, Greece
| | - Barbara Driagka
- Fourth Department of Surgery, Medical School, Aristotle University of Thessaloniki, Thessaloniki 57010, Greece
| | - Ourania Kerasidou
- Fourth Department of Surgery, Medical School, Aristotle University of Thessaloniki, Thessaloniki 57010, Greece
| | - Savvas Symeonidis
- Fourth Department of Surgery, Medical School, Aristotle University of Thessaloniki, Thessaloniki 57010, Greece
| | - Stefanos Bitsianis
- Fourth Department of Surgery, Medical School, Aristotle University of Thessaloniki, Thessaloniki 57010, Greece
| | - Freideriki Sifaki
- Fourth Department of Surgery, Medical School, Aristotle University of Thessaloniki, Thessaloniki 57010, Greece
| | - Konstantinos Angelopoulos
- Fourth Department of Surgery, Medical School, Aristotle University of Thessaloniki, Thessaloniki 57010, Greece
| | - Haralabos Demetriades
- Fourth Department of Surgery, Medical School, Aristotle University of Thessaloniki, Thessaloniki 57010, Greece
| | - Stamatios Angelopoulos
- Fourth Department of Surgery, Medical School, Aristotle University of Thessaloniki, Thessaloniki 57010, Greece
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Celen S, Ozlulerden Y, Baser A, Alkış O, Kucuker K, Duran MB. Can Neoadjuvant Chemotherapy Cause Postoperative Hydronephrosis After Radical Cystectomy? Cureus 2024; 16:e57306. [PMID: 38690486 PMCID: PMC11059171 DOI: 10.7759/cureus.57306] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/30/2024] [Indexed: 05/02/2024] Open
Abstract
OBJECTIVE This study's objective is to assess the effect of preoperative factors on postoperative hydroureteronephrosis (HUN) after radical cystectomy (RC) in patients with bladder cancer (BC). METHODOLOGY Patients who underwent RC for BC between January 2019 and November 2022 and had unilateral or bilateral postoperative HUN were retrospectively analyzed. Patients without preoperative HUN but with postoperative HUN constituted the patient group, while patients without both preoperative and postoperative HUN constituted the control group, and they were compared with each other. RESULTS Neoadjuvant chemotherapy (NAC) and postoperative metastasis were positively correlated with postoperative HUN (r = 0.238, P = 0.007, and r = 0.203, P = 0.021, respectively). Multivariate logistic regression analysis showed that the postoperative HUN was significantly associated with NAC (P = 0.048; Exp(B) = 6.896, 95% confidence interval [CI] 1.02-46.9) but not associated with the presence of metastasis (P = 0.054). Moreover, NAC increased the possibility of undergoing revision surgery (P = 0.002; Exp(B) = 26.9, 95% CI 3.2-225). CONCLUSIONS NAC is an independent factor for impaired anastomotic healing, increased postoperative HUN, and the need for revision surgery in patients with BC.
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Affiliation(s)
- Sinan Celen
- Urology, Pamukkale University School of Medicine, Denizli, TUR
| | | | - Aykut Baser
- Urology, Bandirma Onyedi Eylul University School of Medicine, Balikesir, TUR
| | - Okan Alkış
- Urology, Kutahya Health Science University, Kütahya, TUR
| | - Kursat Kucuker
- Urology, Pamukkale University School of Medicine, Denizli, TUR
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Pochard C, Gonzales J, Bessard A, Mahe MM, Bourreille A, Cenac N, Jarry A, Coron E, Podevin J, Meurette G, Neunlist M, Rolli-Derkinderen M. PGI 2 Inhibits Intestinal Epithelial Permeability and Apoptosis to Alleviate Colitis. Cell Mol Gastroenterol Hepatol 2021; 12:1037-1060. [PMID: 33971327 PMCID: PMC8342971 DOI: 10.1016/j.jcmgh.2021.05.001] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2020] [Revised: 05/01/2021] [Accepted: 05/03/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND & AIMS Inflammatory bowel diseases (IBDs) that encompass both ulcerative colitis and Crohn's disease are a major public health problem with an etiology that has not been fully elucidated. There is a need to improve disease outcomes and preventive measures by developing new effective and lasting treatments. Although polyunsaturated fatty acid metabolites play an important role in the pathogenesis of several disorders, their contribution to IBD is yet to be understood. METHODS Polyunsaturated fatty acids metabolite profiles were established from biopsy samples obtained from Crohn's disease, ulcerative colitis, or control patients. The impact of a prostaglandin I2 (PGI2) analog on intestinal epithelial permeability was tested in vitro using Caco-2 cells and ex vivo using human or mouse explants. In addition, mice were treated with PGI2 to observe dextran sulfate sodium (DSS)-induced colitis. Tight junction protein expression, subcellular location, and apoptosis were measured in the different models by immunohistochemistry and Western blotting. RESULTS A significant reduction of PGI2 in IBD patient biopsies was identified. PGI2 treatment reduced colonic inflammation, increased occludin expression, decreased caspase-3 cleavage and intestinal permeability, and prevented colitis development in DSS-induced mice. Using colonic explants from mouse and human control subjects, the staurosporine-induced increase in paracellular permeability was prevented by PGI2. PGI2 also induced the membrane location of occludin and reduced the permeability observed in colonic biopsies from IBD patients. CONCLUSIONS The present study identified a PGI2 defect in the intestinal mucosa of IBD patients and demonstrated its protective role during colitis.
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Affiliation(s)
- Camille Pochard
- Université de Nantes, Inserm, TENS, The Enteric Nervous System in Gut and Brain Disorders, Institut des Maladies de l'Appareil Digestif, Nantes, France
| | - Jacques Gonzales
- Université de Nantes, Inserm, TENS, The Enteric Nervous System in Gut and Brain Disorders, Institut des Maladies de l'Appareil Digestif, Nantes, France
| | - Anne Bessard
- Université de Nantes, Inserm, TENS, The Enteric Nervous System in Gut and Brain Disorders, Institut des Maladies de l'Appareil Digestif, Nantes, France
| | - Maxime M Mahe
- Université de Nantes, Inserm, TENS, The Enteric Nervous System in Gut and Brain Disorders, Institut des Maladies de l'Appareil Digestif, Nantes, France; Department of Pediatric General and Thoracic Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio; Department of Pediatrics, University of Cincinnati, Cincinnati, Ohio
| | - Arnaud Bourreille
- Université de Nantes, Inserm, TENS, The Enteric Nervous System in Gut and Brain Disorders, Institut des Maladies de l'Appareil Digestif, Nantes, France; CHU de Nantes, Hôpital Hôtel-Dieu, Nantes, France; CIC 1413, Nantes, France
| | - Nicolas Cenac
- UMR1220, IRSD, INSERM, INRA, INP-ENVT, Université de Toulouse, Toulouse, France
| | - Anne Jarry
- Université de Nantes, Inserm, CRCINA, Nantes, France
| | - Emmanuel Coron
- Université de Nantes, Inserm, TENS, The Enteric Nervous System in Gut and Brain Disorders, Institut des Maladies de l'Appareil Digestif, Nantes, France; CHU de Nantes, Hôpital Hôtel-Dieu, Nantes, France
| | | | - Guillaume Meurette
- Université de Nantes, Inserm, TENS, The Enteric Nervous System in Gut and Brain Disorders, Institut des Maladies de l'Appareil Digestif, Nantes, France; CHU de Nantes, Hôpital Hôtel-Dieu, Nantes, France
| | - Michel Neunlist
- Université de Nantes, Inserm, TENS, The Enteric Nervous System in Gut and Brain Disorders, Institut des Maladies de l'Appareil Digestif, Nantes, France
| | - Malvyne Rolli-Derkinderen
- Université de Nantes, Inserm, TENS, The Enteric Nervous System in Gut and Brain Disorders, Institut des Maladies de l'Appareil Digestif, Nantes, France.
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Nerstrøm M, Krarup PM, Jorgensen LN, Ågren MS. Therapeutic improvement of colonic anastomotic healing under complicated conditions: A systematic review. World J Gastrointest Surg 2016; 8:389-401. [PMID: 27231518 PMCID: PMC4872068 DOI: 10.4240/wjgs.v8.i5.389] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2015] [Revised: 11/14/2015] [Accepted: 03/09/2016] [Indexed: 02/07/2023] Open
Abstract
AIM: To identify therapeutic agents for the prophylaxis of gastrointestinal anastomotic leakage (AL) under complicated conditions.
METHODS: The PubMed and EMBASE databases were searched for English articles published between January 1975 and September 2014. Studies with the primary purpose of improving anastomotic healing in the colon or rectum under complicated preoperative and/or intraoperative conditions were included. We excluded studies investigating the adverse effects or risk assessment of an active intervention. Furthermore, investigations of biophysical materials, sealants, electrical stimulation and nutrients were excluded. The primary study outcome was biomechanical anastomotic strength or AL. The meta-analysis focused on therapeutic agents that were investigated in one animal model using the same outcome by at least three independent research groups.
RESULTS: The 65 studies included were divided into 7 different complicated animal models: Bowel ischemia, ischemia/reperfusion, bowel obstruction, obstructive jaundice, peritonitis, chemotherapy and radiotherapy. In total, 48 different therapeutic compounds were examined. The majority of investigated agents (65%) were reported as beneficial for anastomotic healing. Twelve of the agents (25%) were tested more than once in the same model, whereas 13 (27%) of the agents were tested in two or more models of complicated healing. Two therapeutic agents met our inclusion criteria for the meta-analysis. Postoperative hyperbaric oxygen therapy significantly increased anastomotic bursting pressure in ischemic colon anastomoses by a mean of 28 mmHg (95%CI: 17 to 39 mmHg, P < 0.00001). Granulocyte macrophage-colony stimulating factor failed to show a significant increase in anastomotic bursting pressure (95%CI: -20 to 21 mmHg, P = 0.97) vs controls in experimental chemotherapeutic models.
CONCLUSION: This systematic review identified potential therapeutic agents, but more studies are needed before concluding that any of these are useful for AL prophylaxis.
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Øines MN, Krarup PM, Jorgensen LN, Ågren MS. Pharmacological interventions for improved colonic anastomotic healing: A meta-analysis. World J Gastroenterol 2014; 20:12637-12648. [PMID: 25253969 PMCID: PMC4168102 DOI: 10.3748/wjg.v20.i35.12637] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2014] [Revised: 04/10/2014] [Accepted: 05/14/2014] [Indexed: 02/06/2023] Open
Abstract
AIM: To identify pharmaceuticals for the prophylaxis of anastomotic leakage (AL), we systematically reviewed studies on anastomosis repair after colorectal surgery.
METHODS: We searched PubMed and EMBASE for articles published between January 1975 and December 2012. We included studies in English with the primary purpose of promoting healing of anastomoses made in the colon or rectum under uncomplicated conditions. We excluded studies on adverse events from interventions, nutritional interventions or in situ physical supporting biomaterials. The primary outcome was biomechanical strength or AL. We performed meta-analyses on therapeutic agents investigated by three or more independent research groups using the same outcome. The DerSimonian-Laird method for random effects was applied with P < 0.05.
RESULTS: Of the 56 different therapeutic agents assessed, 7 met our inclusion criteria for the meta-analysis. The prostacyclin analog iloprost increased the weighted mean of the early bursting pressure of colonic anastomoses in male rats by 60 mmHg (95%CI: 30-89) vs the controls, and the immunosuppressant tacrolimus increased this value by 29 mmHg (95%CI: 4-53) vs the controls. Erythropoietin showed an enhancement of bursting pressure by 45 mmHg (95%CI: 14-76). The anabolic compound growth hormone augmented the anastomotic strength by 21 mmHg (95%CI: 7-35), possibly via the up-regulation of insulin-like growth factor-1, as this growth factor increased the bursting pressure by 61 mmHg (95%CI: 43-79) via increased collagen deposition. Hyperbaric oxygen therapy increased the bursting pressure by 24 mmHg (95%CI: 13-34). Broad-spectrum matrix metalloproteinase inhibitors increased the bursting pressure by 48 mmHg (95%CI: 31-66) on postoperative days 3-4. In the only human study, the AL incidence was not significantly reduced in the 103 colorectal patients treated with aprotinin (11.7%) compared with the 113 placebo-treated patients (9.7%).
CONCLUSION: This systematic review identified only one randomized clinical trial and seven therapeutic agents from pre-clinical models that could be explored further for the prophylaxis of AL after colorectal surgery.
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Sabino FD, Campos CFF, Caetano CER, Trotte MNS, Oliveira AV, Marques RG. Effects of TachoSil and 5-fluorouracil on colonic anastomotic healing. J Surg Res 2014; 192:375-82. [PMID: 24976442 DOI: 10.1016/j.jss.2014.05.067] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2013] [Revised: 04/16/2014] [Accepted: 05/21/2014] [Indexed: 02/08/2023]
Abstract
BACKGROUND The administration of intraperitoneal (IP) 5-fluorouracil (5-FU) during the early postoperative period after cytoreductive surgery can decrease local cancer recurrence but may also cause impairment of the anastomotic healing. This study examined the effects of the use of this therapy and of the anastomotic sealing with TachoSil, a fibrin-thrombin coated sealant (FTCS), on the healing of colon anastomoses. MATERIALS AND METHODS Forty male rats were divided into four groups (1-4, 10 rats each) that underwent transection and anastomosis of the left colon. The anastomoses were covered with FTCS in groups 2 and 4. Saline solution (2 mL/d-groups 1 and 2) or 5-FU (20 mg/kg/d; groups 3 and 4) was administered IP once daily for 3 d. Bursting pressure (BP) was recorded, and the anastomoses were examined macroscopically and graded histologically. RESULTS The relative weight loss was significantly higher in group 3 than in the other groups (P = 0.0004). Anastomotic dehiscence, postoperative adhesion formation, perianastomotic collections, and preanastomotic dilatation did not differ significantly among groups. BP was significantly lower in group 3 compared with all other groups (P = 0.001). Neoangiogenesis was significantly lower in group 3 compared with groups 1 and 2 (P = 0.05). Fibroblastic activity was significantly higher in group 1 compared with group 3 (P = 0.035). Inflammatory cell infiltration and collagen deposition did not differ significantly among groups. CONCLUSIONS Our results shown that the early postoperative IP chemotherapy with 5-FU impaired the healing of colon anastomoses. However, anastomotic sealing with FTCS reversed some of the negative effects of this therapy.
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Affiliation(s)
- Flávio D Sabino
- Department of Abdominal and Pelvic Surgery, National Cancer Institute, Rio de Janeiro, Brazil; Department of General Surgery, Federal Hospital of Rio de Janeiro State Civil Servers, Rio de Janeiro, Brazil.
| | | | - Carlos Eduardo R Caetano
- Department of General Surgery, Laboratory of Experimental Surgery, Rio de Janeiro State University, Rio de Janeiro, Brazil
| | - Marcele Nogueira S Trotte
- Department of General Surgery, Laboratory of Experimental Surgery, Rio de Janeiro State University, Rio de Janeiro, Brazil
| | - Albanita V Oliveira
- Department of Pathology, Rio de Janeiro State University, Rio de Janeiro, Brazil
| | - Ruy G Marques
- Department of General Surgery, Rio de Janeiro State University, Rio de Janeiro, Brazil
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Galanopoulos G, Raptis D, Pramateftakis MG, Mantzoros I, Kanellos I, Lazarides C. The effects of iloprost on colonic anastomotic healing in rats under obstructive ileus conditions. J Surg Res 2014; 189:22-31. [PMID: 24582070 DOI: 10.1016/j.jss.2014.01.052] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2013] [Revised: 01/07/2014] [Accepted: 01/30/2014] [Indexed: 01/11/2023]
Abstract
BACKGROUND The aim of this study was to investigate the effects of iloprost, on colonic anastomotic healing in rats, under obstructive ileus conditions. MATERIALS AND METHODS Eighty male Albino rats were randomized into four groups of 20 animals each. They underwent colonic resection followed by an inverted anastomosis. The rats of group 1 (control) and group 2 (ileus) received 3 mL of saline 0.9% intraperitoneally and those of group 3 (iloprost), and group 4 (ileus + iloprost) iloprost (2 μg/kg of body weight), immediately postoperatively and daily until the day of sacrifice. Each group was further divided into two equal subgroups, depending on the day of sacrifice. The animals of subgroup "a" were sacrificed on the fourth postoperative day, whereas those of "b" on the eighth day. Macroscopic and histologic assessment was performed, whereas anastomotic bursting pressures and the tissue concentrations in hydroxyproline and collagenase I were evaluated. RESULTS Means of bursting pressure, neoangiogenesis, fibroblast activity, and hydroxyproline concentration were significantly increased in group 4 compared with group 2. In addition, on the fourth postoperative day, the inflammatory cell infiltration and the collagenase I concentration were significantly decreased in group 4 compared with group 2. Moreover, on the eighth postoperative day, collagen deposition was significantly increased in group 4 compared with group 2. CONCLUSIONS Iloprost after intraperitoneal administration reverses the negative effect of obstructive ileus. It promotes not only the angiogenic activity but also collagen formation, resulting in increased bursting pressures on the fourth and eighth postoperative days.
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Affiliation(s)
- Georgios Galanopoulos
- 4th Surgical Department, G. Hospital "G. Papanikolaou", Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Dimitrios Raptis
- 4th Surgical Department, G. Hospital "G. Papanikolaou", Aristotle University of Thessaloniki, Thessaloniki, Greece; Surgical Department, Friedrich-Alexander University of Erlangen-Nuremberg, Erlangen, Germany.
| | | | - Ioannis Mantzoros
- 4th Surgical Department, G. Hospital "G. Papanikolaou", Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Ioannis Kanellos
- 4th Surgical Department, G. Hospital "G. Papanikolaou", Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Charalambos Lazarides
- 4th Surgical Department, G. Hospital "G. Papanikolaou", Aristotle University of Thessaloniki, Thessaloniki, Greece
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Son KH, Jeong HW, Jung WW, Kim HS, Lee SK, Kim KT, Ahn CB, Park KY, Kim BM, Lee SH. The use of collagen content as determined by spectral domain polarization-sensitive optical coherence tomography to assess colon anastomosis healing in a rat model. Eur Surg Res 2014; 52:32-40. [PMID: 24480934 DOI: 10.1159/000358057] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2013] [Accepted: 12/17/2013] [Indexed: 11/19/2022]
Abstract
BACKGROUND/PURPOSE Many studies have been undertaken to prevent anastomosis leakage of the colon, and several methods have been used to assess anastomosis healing, such as measurement of bursting pressure or hydroxyproline (a marker of collagen) content at the anastomosis site. However, these methods are inappropriate for comparing anastomosis healing at two time points in the same animals. In the present study, we measured the collagen level by spectral domain polarization-sensitive optical coherence tomography (SD-PS-OCT) to assess anastomosis healing. METHODS Sprague-Dawley rats were divided into groups C (saline-administered controls; study group) and M [a 5-fluorouracil (5-FU)-administered experimental group]. Immediately after end-to-end anastomosis of the colon, SD-PS-OCT images of anastomoses were taken (baseline). Animals were administered saline or 5-FU for 7 days. On the 7th postoperative day, SD-PS-OCT images were acquired, a histopathologic exam was performed, and hydroxyproline levels as well as mRNA expressions of collagen-1 and collagen-3 were measured at the anastomosis site. RESULTS Fibroblast proliferation and inflammatory cell infiltration were greater in group C than in group M. The mRNA expressions of collagen-1 and collagen-3 were substantially higher in group C. Hydroxyproline levels were higher in group M than in group C. Though collagen levels measured by SD-PS-OCT at 7 days were elevated compared with baseline in group C, no such changes were observed for group M. CONCLUSION Collagen levels at the colon anastomosis site, measured with SD-PS-OCT, were not increased at 7 days postoperatively versus baseline when 5-FU was injected, but were increased in saline-treated controls. The measurement of collagen content by SD-PS-OCT was found to provide a good means of assessing anastomosis healing, because it allows in situ assessment of collagen contents at baseline and during the postoperative period.
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Affiliation(s)
- K H Son
- Department of Thoracic and Cardiovascular Surgery, Gachon University Gil Medical Center, Gachon University, Incheon, South Korea
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Karatepe O, Cakir A, Unal O, Battal M, Adas G, Kamali G, Kemik A, Aydin T, Kamali S, Karahan SR, Aksoy M. Iloprost reduces colonic injury in ischemic colitis in rats. Acta Cir Bras 2012; 26:220-6. [PMID: 21537525 DOI: 10.1590/s0102-86502011000300011] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2010] [Accepted: 02/14/2011] [Indexed: 01/06/2023] Open
Abstract
PURPOSE Evaluate the effects of iloprost administration in the early period of ischemic colitis and the mechanism that how these effects develop. METHODS Thirty two Wistar albino female rats with an average weight of 220g were divided into four groups of eight rats. In group 1 the rats were given iloprost and sacrificed after 24 hours and in group 2 they were sacrificed after 24 hours without any iloprost. The rats in group 3 were administrated iloprost and sacrificed after 72 hours and in group 4 they were sacrificed at 72th hour without iloprost. The differences between the groups as tissue damage, vascularization or apoptosis were assessed statistically. RESULTS Oxidative damage and apoptosis were less pronounced and vascularization was better developed in rats that were given iloprost and sacrificed at 24th hour later in contrast to the rats that were not treated with iloprost. But there was no statistical difference among the groups at 72th hour. CONCLUSION Iloprost inhibited leucocyte infiltration, decreased proinflammatory cytokines and enhanced angiogenesis so that the oxidative stress and inflammatory response decreased resulting in lesser tissue damage.
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Affiliation(s)
- Oguzhan Karatepe
- Okmeydani Research Hospital, General Surgery Department, Istanbul, Turkey.
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Blouhos K, Pramateftakis MG, Tsachalis T, Kanellos D, Zaraboukas T, Koliakos G, Betsis D. The integrity of colonic anastomoses following the intraperitoneal administration of oxaliplatin. Int J Colorectal Dis 2010; 25:835-41. [PMID: 20217424 DOI: 10.1007/s00384-010-0912-y] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 02/11/2010] [Indexed: 02/07/2023]
Abstract
INTRODUCTION The purpose of this experimental study was to determine the effect of oxaliplatin on the integrity of colonic anastomoses which were under oxaliplatin administration. MATERIALS AND METHODS Thirty rats were randomized to two groups. After resection of a 1-cm segment of the transverse colon, an end-to-end sutured anastomosis was performed. Rats of the control group were injected with 3 ml of 0.9% sodium chloride solution and in the oxaliplatin group with 2.4 mg/kg of oxaliplatin intraperitoneally immediately after surgery and for seven postoperative days. All rats were sacrificed on the tenth postoperative day, and the anastomoses were examined macroscopically and graded histologically. Rats were measured for anastomotic bursting pressures and tissue hydroxyproline levels. RESULTS The body weight changes were significantly greater in the oxaliplatin group (p = 0.005). Anastomotic dehiscence occurred only in the oxaliplatin group. The adhesion formation was significantly increased in the group of oxaliplatin compared to the control group (p = 0.001). The colonic bursting pressure was significantly lower in the oxaliplatin group compared to the control group (p < 0.001). The mean inflammatory cell infiltration was significantly lower in the oxaliplatin group (1.00 vs. 2.33, p < 0.001). The mean neoagiogenesis was significantly lower in the oxaliplatin group (0.80 vs. 2.20, p < 0.001). The mean collagen deposition was significantly lower in the oxaliplatin group and the mean fibroblast activity was significantly lower in the oxaliplatin group (1.27 vs. 2.53, p < 0.001). Hydroxyproline concentration was significantly lower in the oxaliplatin group (p < 0.001). CONCLUSION Intra- and postoperative intraperitoneal administration of oxaliplatin definitely impairs healing of colonic anastomoses in rats.
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Affiliation(s)
- Konstantinos Blouhos
- Fourth Department of Surgery, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece.
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Healing of colonic anastomoses after immediate postoperative intraperitoneal administration of oxaliplatin. Int J Colorectal Dis 2008; 23:1185-91. [PMID: 18677490 DOI: 10.1007/s00384-008-0538-5] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 07/03/2008] [Indexed: 02/04/2023]
Abstract
AIM The aim of this experimental study was to investigate the effect of intraperitoneal administration of oxaliplatin on the healing of colonic anastomoses when injected immediately after colon resection. MATERIALS AND METHODS Thirty male Wistar rats were used. During the operation, the rats were randomized to two groups of 15 rats each. Immediately after colonic anastomoses were performed, the rats were injected intraperitoneally with either 3 ml of 0.9% NaCl solution or oxaliplatin (2.4 mg/kg body weight) depending on their group. All rats were killed on the eighth postoperative day. The anastomoses were examined macroscopically. The anastomotic bursting pressures were recorded, the anastomoses graded histologically, and the hydroxyproline tissue contents determined. RESULTS Anastomotic leakage was noted in four rats (26.7%) of the oxaliplatin group, whereas no anastomotic dehiscence was detected among rats of the control group (p = 0.016). The adhesion formation at the anastomotic sites and the inflammatory cell infiltration were significantly higher in the oxaliplatin group than in the control group (p = 0.001). The bursting pressures (p = 0.001), the hydroxyproline tissue content (p = 0.001), the neoangiogenesis (p = 0.033), the fibroblast activity (p = 0.001), and the collagen deposition (p = 0.001) were significantly lower in the oxaliplatin group in comparison to the control group. CONCLUSION The immediate postoperative intraperitoneal administration of oxaliplatin seems to impair healing of colonic anastomoses in rats.
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Zacharakis E, Demetriades H, Pramateftakis MG, Lambrou I, Zacharakis E, Zaraboukas T, Koliakos G, Kanellos I, Betsis D. Effect of IGF-I on healing of colonic anastomoses in rats under 5-FU treatment. J Surg Res 2007; 144:138-44. [PMID: 17640667 DOI: 10.1016/j.jss.2007.03.045] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2006] [Revised: 01/29/2007] [Accepted: 03/19/2007] [Indexed: 01/02/2023]
Abstract
BACKGROUND The aim of this experimental study was to investigate whether insulin-like growth factor I (IGF-I) can protect the colonic healing from the adverse effects of intraperitoneal administration of 5-fluorouracil (5-FU). MATERIALS AND METHODS Eighty male Wistar rats were randomized into four groups of 20 rats each. Immediately after anastomoses were performed, rats in the control group were injected with 1 mL/100 gr of intraperitoneal saline solution, which was repeated daily until killed. Rats in the 5-FU and IGF-I +5-FU groups received 5-FU in a dose of 20 mg/kg body weight intraperitoneally, from the day of operation until killed. Rats in the IGF-I and IGF-I +5-FU groups received IGF-I in a dose of 2 mg/kg body weight intraperitoneally, immediately after the colonic anastomosis was performed and on 2nd, 4th, and 6th postoperative day. Rats were sacrificed on the 7th postoperative day. RESULTS The dehiscence rate in the 5-FU group was 30% and it was significantly higher compared with the control and the IGF-I group (P = 0.020 for both comparisons). However, in the IGF-I +5-FU group, the dehiscence rate decreased to 10%. The administration of IGF-I resulted in a significant rise of bursting pressure in the IGF-I +5-FU group compared with the 5-FU group (P < 0.001). There was no statistical difference in bursting pressure between the IGF-I +5-FU and control groups (P = 1.000). The hydroxyproline levels were higher in the IGF-I and the IGF-I +5-FU groups as a result of the stimulating act of IGF-I. CONCLUSION IGF-I, when given intraperitoneally, seems to mediate some of the adverse effects of 5-FU on the colonic healing in rats.
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Affiliation(s)
- Emmanouil Zacharakis
- 4th Academic Surgical Unit, Aristotle University of Thessaloniki, G. Papanikolaou General Hospital, Makedonia, Greece.
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Sahin M, Erikoglu M, Ozer S, Tekin A, Boz S, Gölcük M, Avunduk MC, Aköz M. Determination of operation time in colorectal diseases: Preoperative chemotherapy application. J Surg Res 2005; 124:209-15. [PMID: 15820250 DOI: 10.1016/j.jss.2004.09.021] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2004] [Indexed: 11/23/2022]
Abstract
BACKGROUND Our aim was to determine the time it takes for wound healing to return to normal in cases where patients have undergone preoperative chemotherapy. MATERIALS AND METHODS Eighty-four Wistar-albino rats were included in the study. Twelve of them were placed in the control group (Group I), with no further drug administration. Another 12 rats were placed in a sham group (Group II) and were peritoneally injected with 1 cc of isotonic saline solution 5 days a month, for a period of 6 months. The remaining 60 rats were placed in five chemotherapy groups (Groups III-VII) and were administered 20 mg/kg 5-fluorouracil through peritoneal injection, 5 days a month for a period of 6 months. At the end of the sixth cure, 12 rats from the control (Group I), sham (Group II), and chemotherapy groups (Group III) were operated on, and an intestinal transsection was applied to the rectosigmoid junction, followed by one-by-one anastomosis using 5/0 vicryl. Other groups (Groups IV-VI) with chemotherapy treatment were operated on at 1-week intervals and subjected to the same procedure. The subjects were reoperated on on the eleventh day. A full-layer 4 x 4 cm piece was removed from the abdominal wall containing the previous incision line at the middle, for tensile strength pressure measurements. In addition, a 4 cm colon segment was removed for bursting pressure measurements. Plasma albumin and tissue hydroxyproline levels were measured, and fibroblast numbers were counted in the sections prepared from the abdominal wall. RESULTS The control and sham groups were found to be similar to each other with respect to all parameters measured (P > 0.05). Significant reductions were observed in all parameters in the early chemotherapy groups compared with the control and sham groups (P <0.05). All parameters measured in Groups V, VI, and VII were found to be similar to those in the control and sham groups (P <0.05). CONCLUSION Wound healing is impaired in rats with chemotherapy, but following the second week after the chemotherapy, disrupted parameters return to their normal levels.
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Affiliation(s)
- Mustafa Sahin
- Meram Medical Faculty, Selcuk University, Konya, Turkey
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