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Imaoka K, Shimomura M, Okuda H, Yano T, Shimizu W, Yoshimitsu M, Ikeda S, Nakahara M, Kohyama M, Kobayashi H, Shimizu Y, Kochi M, Sumitani D, Mukai S, Takakura Y, Ishizaki Y, Kodama S, Fujimori M, Ishikawa S, Adachi T, Ohdan H. Multivisceral resection as a key indicator of recurrence in locally advanced colorectal cancers with pathologic T3 tumors. J Gastrointest Surg 2025; 29:102015. [PMID: 40081790 DOI: 10.1016/j.gassur.2025.102015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2025] [Revised: 02/23/2025] [Accepted: 03/07/2025] [Indexed: 03/16/2025]
Abstract
PURPOSE This study aimed to elucidate the clinical outcomes of patients with pathologic T3 (pT3) and pathologic T4 (pT4) tumors who underwent radical resection with multivisceral resection (MVR) and to assess the prognostic significance of MVR in locally advanced colorectal cancers (CRCs) in pT3 and pT4 tumors. METHODS This multicenter retrospective analysis evaluated the characteristics, clinicopathologic stages, perioperative factors, and clinical outcomes of patients who underwent primary colorectal resection. Patients were divided into 4 groups: those with a pT3 tumor who did not undergo MVR (pT3 - MVR; n = 1108), those with a pT3 tumor who underwent MVR (pT3 + MVR; n = 56), those with a pT4 tumor who did not undergo MVR (pT4 - MVR; n = 306), and those with a pT4 tumor who did underwent MVR (pT4 + MVR; n = 123). Univariate and multivariate regression analyses were performed to identify risk factors for recurrence. RESULTS The pT3 + MVR group exhibited a higher 5-year recurrence rate than the pT3 - MVR group, with recurrence rates similar to those of the pT4 - MVR or pT4 + MVR groups (pT3 - MVR, 17.4%; pT3 + MVR, 31.6%; pT4 - MVR, 33.4%; pT4 + MVR, 35.1%). Multivariate analysis identified MVR as an independent risk factor for recurrence, particularly peritoneal dissemination, in pT3 tumors, whereas MVR had less effect on recurrence in pT4 tumors. CONCLUSION pT3 tumors requiring MVR had a higher recurrence rate than pT4 tumors. The surgeon's clinical assessment of potential T4 tumors requiring MVR at the time of surgery was an important prognostic indicator in advanced CRC.
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Affiliation(s)
- Kouki Imaoka
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Manabu Shimomura
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
| | - Hiroshi Okuda
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Takuya Yano
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Wataru Shimizu
- Department of Surgery, Hiroshima City North Medical Center Asa Citizens Hospital, Hiroshima, Japan
| | - Masanori Yoshimitsu
- Department of Surgery, Hiroshima City Hiroshima Citizens Hospital, Hiroshima, Japan
| | - Satoshi Ikeda
- Department of Gastroenterological Surgery, Hiroshima Prefectural Hospital, Hiroshima, Japan
| | | | - Mohei Kohyama
- Department of Surgery, Hiroshima General Hospital, Hatsukaichi, Japan
| | | | - Yosuke Shimizu
- Department of Surgery, Kure Medical Center/Chugoku Cancer Center, Institute for Clinical Research, Kure, Japan
| | - Masatoshi Kochi
- Department of Surgery, National Hospital Organization Higashihiroshima Medical Center, Higashihiroshima, Japan
| | | | | | - Yuji Takakura
- Department of Surgery, Chuden Hospital, Hiroshima, Japan
| | - Yasuyo Ishizaki
- Department of Surgery, National Hospital Organization Hiroshima-Nishi Medical Center, Otake, Japan
| | - Shinya Kodama
- Department of Surgery, Yoshida General Hospital, Akitakata, Japan
| | - Masahiko Fujimori
- Department of Surgery, Kure Medical Association Hospital, Kure, Japan
| | - Sho Ishikawa
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Tomohiro Adachi
- Department of Surgery, Hiroshima City North Medical Center Asa Citizens Hospital, Hiroshima, Japan
| | - Hideki Ohdan
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
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Sturm MC, Abazid A, Stope MB. Tissue adhesion after surgical interventions (Review). Exp Ther Med 2025; 29:97. [PMID: 40165802 PMCID: PMC11956145 DOI: 10.3892/etm.2025.12847] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2024] [Accepted: 02/28/2025] [Indexed: 04/02/2025] Open
Abstract
Tissue adhesion after surgical procedures is a common postoperative complication that affects a significant number of patients across all surgical disciplines. In pelvic surgical procedures, second-look surgeries have revealed adhesions in more than half of all patients weeks to several months after surgery. Adhesions can be asymptomatic, but they can also cause a wide range of complications, such as severe pain, nausea, vomiting, constipation, ileus and reproductive dysfunction. Undetected adhesions that lead to problems in subsequent surgical interventions are also of high clinical importance. Lysis of these adhesions before the actual surgery leads to loss of time and possible additional complications, such as trocar injuries in laparoscopies or inadvertent enterotomies during adhesiolysis, during the originally planned intervention. The health care associated with adhesion-related problems are significant. Because of the widely varying manifestations of symptoms, the already concerning figure of patients with significant adhesions is likely to increase. Outpatient healthcare expenditures are further increased because of undetected adhesions. Adhesions therefore represent a major surgical and health economic problem; however, yet there are currently few options for prophylaxis and treatment.
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Affiliation(s)
- Malin C.K. Sturm
- Department of Gynecology and Gynecological Oncology, University Hospital Bonn, D-53127 Bonn, Germany
| | - Alexander Abazid
- Department of General, Visceral and Thorax Surgery, Bundeswehr Hospital Berlin, D-10115 Berlin, Germany
| | - Matthias B. Stope
- Department of Gynecology and Gynecological Oncology, University Hospital Bonn, D-53127 Bonn, Germany
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Hausburg MA, Banton KL, Cassidy CD, Madayag RM, Palacio CH, Williams JS, Bar-Or R, Ryznar RJ, Bar-Or D. Mesothelial cell responses to acute appendicitis or small bowel obstruction reactive ascites: Insights into immunoregulation of abdominal adhesion. PLoS One 2025; 20:e0317056. [PMID: 39775680 PMCID: PMC11709316 DOI: 10.1371/journal.pone.0317056] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2024] [Accepted: 12/19/2024] [Indexed: 01/11/2025] Open
Abstract
Previous abdominal surgery (PAS) increases risk of small bowel obstruction (SBO) due to adhesions, and appendectomy (appy) is an independent risk factor for abdominal adhesion-related complications. Peritoneal inflammation, e.g., acute appendicitis (AA), causes formation of reactive ascitic fluid (rA) that activates peritoneum surface mesothelial cells (MCs) to form adhesions. Pathologic adhesions may arise if restoration of MC-regulated fibrinolysis and secretion of glycocalyx (GCX) are disrupted. Proteins affecting these processes may originate from peritoneal rA. This is a prospective observational IRB-approved study at three Level 1 trauma centers where rA is collected prior to surgical intervention for non-perforated AA or adhesiolysis for SBO. Samples from 48 appy and 15 SBO patients were used to treat human MCs and subjected to quantification of 85 inflammatory mediators. Results were compared between patients with surgically naïve abdomens (naïve) and patients with >1 PAS. Select rA caused MCs to form clusters of fibroblastic cells, extracellular matrix fibers (FIB), and secretion of GCX. PAS and naïve patient rA fluids were clustered into "fiber-GCX" (FIB-GCX) groups: highFIB-highGCX, highFIB-lowGCX, noFIB-highGCX, noFIB-lowGCX, and noFIB-noGCX. Between groups, 26 analytes were differentially abundant including innate immune response, wound healing, and mucosal defense proteins. Factors that contributed to the differences between groups were rA-induced highFIB and history of PAS. Overall, PAS patient rA showed a muted immune response compared to rA from naïve patients. Our data suggest that abdominal surgery may negatively impact future immune responses in the abdomen. Further, quantifying immunomodulators in peritoneal rA may lead to the development a personalized approach to post-surgical adhesion treatment and prevention.
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Affiliation(s)
- Melissa A. Hausburg
- Trauma Research, Swedish Medical Center, Englewood, Colorado, United States of America
- Trauma Research, Wesley Medical Center, Wichita, Kansas, United States of America
- Trauma Services, Lutheran Hospital, Wheat Ridge, Colorado, United States of America
- Trauma Research, South Texas Health System McAllen, McAllen, Texas, United States of America
| | - Kaysie L. Banton
- Trauma Services, Swedish Medical Center, Englewood, Colorado, United States of America
| | | | - Robert M. Madayag
- Trauma Services, Lutheran Hospital, Wheat Ridge, Colorado, United States of America
- Trauma Services, St. Anthony Hospital, Lakewood, Colorado, United States of America
| | - Carlos H. Palacio
- Trauma Services, South Texas Health System McAllen, McAllen, Texas, United States of America
| | - Jason S. Williams
- Trauma Research, Swedish Medical Center, Englewood, Colorado, United States of America
- Trauma Research, Wesley Medical Center, Wichita, Kansas, United States of America
- Trauma Services, Lutheran Hospital, Wheat Ridge, Colorado, United States of America
- Trauma Research, South Texas Health System McAllen, McAllen, Texas, United States of America
| | - Raphael Bar-Or
- Trauma Research, Swedish Medical Center, Englewood, Colorado, United States of America
- Trauma Research, Wesley Medical Center, Wichita, Kansas, United States of America
- Trauma Services, Lutheran Hospital, Wheat Ridge, Colorado, United States of America
- Trauma Research, South Texas Health System McAllen, McAllen, Texas, United States of America
| | - Rebecca J. Ryznar
- Department of Molecular Biology, Rocky Vista University, Parker, Colorado, United States of America
| | - David Bar-Or
- Trauma Research, Swedish Medical Center, Englewood, Colorado, United States of America
- Trauma Research, Wesley Medical Center, Wichita, Kansas, United States of America
- Trauma Services, Lutheran Hospital, Wheat Ridge, Colorado, United States of America
- Trauma Research, South Texas Health System McAllen, McAllen, Texas, United States of America
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Dai Y, Inagaki NF, Ueki R, Sando S, Hasegawa K, Ito T. Hepatocyte Growth Factor DNA Aptamer for Prevention of Postoperative Peritoneal Adhesion via Enhancement of Fibrinolysis and Inhibition of Mesothelial Mesenchymal Transition. ACS APPLIED BIO MATERIALS 2024; 7:4679-4689. [PMID: 38963794 DOI: 10.1021/acsabm.4c00507] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/06/2024]
Abstract
Postoperative peritoneal adhesion (PPA) is a prevalent complication of abdominal surgery, posing a significant hindrance to postsurgical recovery. Although several strategies have been developed to alleviate and prevent adhesions, their efficacy remains unsatisfactory. For the first time, we studied the therapeutic effect and mechanism of our recently developed thermally stable oligonucleotide-based mimetics of hepatocyte growth factor (HGF DNA aptamer) to prevent PPA. The HGF DNA aptamer effectively inhibited canonical TGF-β1 signaling transduction, partially suppressing mesothelial mesenchymal transition. Additionally, the aptamer, respectively, upregulated and downregulated the expression of tissue plasminogen activator and plasminogen activator inhibitor 1, thereby enhancing fibrinolytic activity. As a pleiotropic factor, the HGF DNA aptamer also enhanced the migratory and proliferative capacities of mesothelial cells. Finally, the aptamer demonstrated a higher level of effectiveness in preventing PPAs than the commercially available antiperitoneal adhesion barrier, Seprafilm. Due to its therapeutic benefits, excellent stability, biosafety, cost-effectiveness, and versatility, the HGF DNA aptamer demonstrates promise for preventing PPA in future clinical settings.
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Affiliation(s)
- Yizhou Dai
- Department of Chemical System Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan
- Department of Bioengineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan
| | - Natsuko F Inagaki
- Department of Chemical System Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan
- Department of Radiology and Biomedical Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
| | - Ryosuke Ueki
- Department of Chemistry & Biotechnology, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan
| | - Shinsuke Sando
- Department of Bioengineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan
- Department of Chemistry & Biotechnology, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan
| | - Kiyoshi Hasegawa
- Hepato-Biliary-Pancreatic Surgery Division, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
| | - Taichi Ito
- Department of Chemical System Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan
- Department of Bioengineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan
- Department of Radiology and Biomedical Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
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Moradi E, Rakhshandeh H, Rahimi Baradaran V, Ghadiri M, Hasanpour M, Iranshahi M, Askari V. HPLC/MS characterization of Syzygium aromaticum L. and evaluation of its effects on peritoneal adhesion: Investigating the role of inflammatory cytokines, oxidative factors, and fibrosis and angiogenesis biomarkers. Physiol Rep 2023; 11:e15584. [PMID: 36695659 PMCID: PMC9875745 DOI: 10.14814/phy2.15584] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2022] [Revised: 01/04/2023] [Accepted: 01/05/2023] [Indexed: 01/26/2023] Open
Abstract
The dried flower bud of Syzygium aromaticum L. (S. aromaticum) (Myrtaceae), cloves, have been used for their analgesic and anti-inflammatory activities. Peritoneal adhesion (PA) is the most common complication of abdominal and pelvic surgeries, which causes significant adverse effects and severe economic burden. The present study aimed to evaluate the preventive effect of S. extract (SAE) on PA formation in a rat model. Male Wistar 8-week-old rats were randomly divided into sham, control (received vehicle), and treatment (0.25%, 0.5%, and 1% w/v of SAE) groups. The adhesion and related factors were examined using the Nair scoring system and immunological and biochemical kits for the levels of inflammatory cytokines [interleukin (IL)-6 and tumor necrosis factor (TNF)-α], growth factors [transforming growth factor (TGF)-β1 and vascular endothelial growth factor (VEGF)], oxidative [nitric oxide (NO) and malondialdehyde (MDA)], and anti-oxidative [glutathione (GSH)] factors. Our results figured out that the adhesion score and IL-6, TNF-α, TGF-β1, VEGF, NO, and MDA levels were significantly increased, but the GSH level was decreased in the control group compared to the sham group (p < 0.001-0.05). On the other hand, the 0.25% SAE group had a lower adhesion score, and IL-6, TNF-α, TGF-β1, VEGF, NO, and MDA levels were significantly decreased compared with the vehicle group, and the level of GSH was increased (p < 0.001-0.05). SAE could efficiently reduce adhesion score and regulate inflammatory cytokines, oxidative and anti-oxidative factors, and biomarkers of fibrosis and angiogenesis. Therefore, clove extract can be considered a potential candidate for PA management.
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Affiliation(s)
- Elham Moradi
- Pharmacological Research Center of Medicinal PlantsMashhad University of Medical SciencesMashhadIran
| | - Hassan Rakhshandeh
- Pharmacological Research Center of Medicinal PlantsMashhad University of Medical SciencesMashhadIran
| | - Vafa Rahimi Baradaran
- Department of Cardiovascular Diseases, Faculty of MedicineMashhad University of Medical SciencesMashhadIran
| | - Mobarakeh Ghadiri
- Pharmacological Research Center of Medicinal PlantsMashhad University of Medical SciencesMashhadIran
| | - Maedeh Hasanpour
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical SciencesMashhadIran
| | - Mehrdad Iranshahi
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical SciencesMashhadIran
| | - Vahid Reza Askari
- International UNESCO Center for Health‐Related Basic Sciences and Human NutritionMashhad University of Medical SciencesMashhadIran
- Applied Biomedical Research CenterMashhad University of Medical SciencesMashhadIran
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Kurtulus I, Basim S, Ozdenkaya Y. Can serum tumor necrosis factor-alpha predict peritoneal adhesions prior to secondary laparoscopic procedures? J Visc Surg 2022:S1878-7886(22)00181-3. [PMID: 36577610 DOI: 10.1016/j.jviscsurg.2022.12.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
AIM OF THE STUDY This study aimed to investigate the incidence and degree of postoperative intra-abdominal adhesions(POAs) in secondary laparoscopic procedures and assess the power of the preoperative levels of tumor necrosis factor-alpha(TNF-α) and interleukin-1 beta(IL-1β) and selected peripheral inflammatory biomarkers(PIBs) in the prediction of the development and extent of POA. PATIENTS AND METHODS This prospective study enrolled 103 patients who had previously undergone at least one or more laparoscopic abdominal or gynecological operations. We examined TNF-α, IL-1β, and PIBs, namely C-reactive protein, white blood cell count, neutrophil-to-lymphocyte ratio(NLR), platelet-to-lymphocyte ratio, and systemic immune-inflammation index(SII) according to the presence, location, and score of adhesions determined during secondary laparoscopic procedures. RESULTS Only age, postoperative adhesion index(PAI) score, NLR, SII, TNF-α, and IL-1β resulted in a significant difference in the existence of adhesion(P<0.05). The correlation analysis of TNF-α with variables showed that the PAI score and IL 1β levels had a significantly positive correlation. CONCLUSION The presence and extent of POA could be predicted by examining the preoperative TNF-α level in patients who had laparoscopic abdominal surgery previously. We could overcome adverse events during secondary laparoscopic procedures by assessing high-risk patients and integrating a personalized surgical approach to managing selected patients.
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Affiliation(s)
- I Kurtulus
- Department of General Surgery, Basaksehir Cam and Sakura City Hospital, Istanbul, Turkey.
| | - S Basim
- Department of General Surgery, Basaksehir State Hospital, Istanbul, Turkey
| | - Y Ozdenkaya
- Department of General Surgery, Istanbul Medipol University, Bagcilar, Istanbul, Turkey
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Hausburg MA, Bocker JM, Madayag RM, Mains CW, Banton KL, Liniewicz TE, Tanner A, Sercy E, Bar-Or R, Williams JS, Ryznar RJ, Bar-Or D. Characterization of Peritoneal Reactive Ascites Collected from Acute Appendicitis and Small Bowel Obstruction Patients. Clin Chim Acta 2022; 531:126-136. [PMID: 35346646 DOI: 10.1016/j.cca.2022.03.022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2021] [Revised: 03/18/2022] [Accepted: 03/23/2022] [Indexed: 11/03/2022]
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Eren EC, Basım P. Role of peripheral inflammatory biomarkers, transforming growth factor-beta and interleukin 6 in predicting peritoneal adhesions following repeat cesarean delivery. Ir J Med Sci 2022; 191:2697-2704. [PMID: 34988860 DOI: 10.1007/s11845-021-02878-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2021] [Accepted: 11/30/2021] [Indexed: 10/19/2022]
Abstract
BACKGROUND Repeat cesarean deliveries (CDs) pose a risk in the development of intra-abdominal adhesions. AIM We aimed to examine the incidence and severity of adhesions in repeat CDs using a specific scoring system and assess the predictive power of the pre-operative value of transforming growth factor (TGF)-β and interleukin (IL)-6 with selected peripheral inflammatory biomarkers (PIBs) in the prediction of adhesion formation. METHODS This prospective study enrolled 91 pregnant women at term, who had previously undergone at least one or more scheduled CDs. PIBs, namely C-reactive protein, white blood cell count, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and systemic immune-inflammation index, TGF-β, and IL-6 were studied according to the presence and location of adhesions. RESULTS There was a significant difference only in the variables of the number of CDs, post-operative adhesion index (PAI) score, IL-6, and TGF-β on the presence of adhesion (p < 0.05). The linear regression model revealed that the effect of the number of CDs, PAI score, and IL-6 values on TGF-β was significant (p < 0.05). The effect of the PAI score on TGF-β was higher than that of IL-6. As a reciprocal relationship, the effect of the TGF-β value on the PAI score was also higher than that of IL-6. CONCLUSION In patients with a history of repeat CDs, the preoperative determination of TGF-β seems to be an important independent predictor of POA. The adverse events due to post-operative adhesion caused by repeat CDs can be overcome by detecting high-risk patients with a comprehensive assessment and individualized intervention integrated into overall patient management.
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Affiliation(s)
- Elif Ciler Eren
- Department of Obstetrics and Gynecology, Medipol University Medical Faculty, Istanbul, Turkey
| | - Pelin Basım
- Department of General Surgery, Medipol University Medical Faculty, Istanbul, Turkey.
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9
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Hashemzaei M, Tabrizian K, Koohkan MJ, Khoshsima Shahraki M, Rezaee R, Ghorani V, Shahraki J. Effects of gallic acid on intraperitoneal adhesion bands in rats. AVICENNA JOURNAL OF PHYTOMEDICINE 2022; 12:337-345. [PMID: 35782766 PMCID: PMC9121263 DOI: 10.22038/ajp.2022.19811] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/16/2020] [Revised: 01/11/2022] [Accepted: 01/18/2022] [Indexed: 11/09/2022]
Abstract
Objective Gallic acid (GA) is an organic acid that possesses anti-inflammatory effects as it inhibits the production of metalloproteinases, tissue plasminogen activator, growth factors and adhesion molecules. Since formation of abdominal surgery-induced adhesion bands is accompanied by inflammation, angiogenesis and cell proliferation, in the current study, we assessed potential beneficial properties of GA against adhesion bands formation in rats. Materials and Methods Thirty-six adult male rats were assigned into six groups of six animals. After induction of anesthesia, peritoneal injury was induced using a standard method and animals received either GA (10, 25, 50 and 100 mg/kg), or normal saline, while a group of rats remained intact. Seven days after the surgery, animals were decapitated and samples were collected for pathology evaluations. Also, lipid peroxidation (TBARS) and tumor necrosis factor alpha (TNF-α) levels were determined in serum samples. Results Our results showed that GA significantly reduced lipid peroxidation in serum samples but had no effect on TNF-α levels. Furthermore, microscopic and macroscopic injuries reduced significantly in GA-treated animals. Conclusion Since GA reduced adhesion bands formation at microscopic and macroscopic levels, it could be considered a treatment against adhesion bands formation.
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Affiliation(s)
- Mahmoud Hashemzaei
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Zabol University of Medical Sciences, Zabol, Iran,Student Research Committee, Faculty of Pharmacy, Zabol University of Medical Sciences, Zabol, Iran,Toxicology and Addiction Research Center, Zabol University of Medical Sciences, Zabol, Iran, Equal first author
| | - Kaveh Tabrizian
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Zabol University of Medical Sciences, Zabol, Iran,Student Research Committee, Faculty of Pharmacy, Zabol University of Medical Sciences, Zabol, Iran,Toxicology and Addiction Research Center, Zabol University of Medical Sciences, Zabol, Iran, Equal first author
| | - Mohammad Javad Koohkan
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Zabol University of Medical Sciences, Zabol, Iran,Student Research Committee, Faculty of Pharmacy, Zabol University of Medical Sciences, Zabol, Iran
| | | | - Ramin Rezaee
- International UNESCO Center for Health-Related Basic Sciences and Human Nutrition, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran,Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Vahideh Ghorani
- International UNESCO Center for Health-Related Basic Sciences and Human Nutrition, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran,Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Jafar Shahraki
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Zabol University of Medical Sciences, Zabol, Iran,Student Research Committee, Faculty of Pharmacy, Zabol University of Medical Sciences, Zabol, Iran,Toxicology and Addiction Research Center, Zabol University of Medical Sciences, Zabol, Iran,Corresponding Author: Tel: +98-5432230774, Fax: +98-5432232161,
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10
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Peker E, Elpek GÖ. The Effect of Ellagic Acid on Intra-abdominal Adhesions Caused by Gallstones. Surg Laparosc Endosc Percutan Tech 2021; 32:166-171. [PMID: 34753896 DOI: 10.1097/sle.0000000000001019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2021] [Accepted: 05/27/2021] [Indexed: 02/05/2023]
Abstract
BACKGROUND Adhesion formation after peritoneal surgery is the main cause of postoperative bowel obstruction, infertility, and chronic pelvic pain. In this study, we evaluated the effect of oral ellagic acid on intra-abdominal adhesions caused by gallstones in rats. MATERIALS AND METHODS Forty-one Wistar-albino rats were used. Gallstones were dropped to the right lower quadrant of the abdomen to create adhesions. They were divided into 4 groups; sham-operated, intraperitoneal gallstone, oral ellagic acid (control), and intraperitoneal gallstone+oral ellagic acid. On the postoperative 10th day, relaparotomy was performed, adhesions were evaluated according to four different macroscopic adhesion score systems and adhesion-bearing tissues were examined histopathologically. Samples were graded for inflammation, vascularization, and fibrosis. RESULTS We found that oral administration of ellagic acid lowered all macroscopic adhesion scores. There were significant differences between groups of sham and gallstone; control and gallstone; control and gallstone+oral ellagic acid (P<0.05). CONCLUSION The ellagic acid administered orally at a dose of 100 mg/kg/d significantly inhibited intra-abdominal adhesion formation and no adverse effects were seen between treatments.
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Affiliation(s)
- Evren Peker
- Department of General Surgery, Marmara University Pendik Research and Education Hospital, Istanbul
| | - Gülsüm Ö Elpek
- Department of Pathology, Medical School, Akdeniz University, Antalya, Turkey
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11
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Fatehi Hassanabad A, Zarzycki AN, Jeon K, Deniset JF, Fedak PWM. Post-Operative Adhesions: A Comprehensive Review of Mechanisms. Biomedicines 2021; 9:biomedicines9080867. [PMID: 34440071 PMCID: PMC8389678 DOI: 10.3390/biomedicines9080867] [Citation(s) in RCA: 69] [Impact Index Per Article: 17.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2021] [Revised: 06/27/2021] [Accepted: 07/15/2021] [Indexed: 11/16/2022] Open
Abstract
Post-surgical adhesions are common in almost all surgical areas and are associated with significant rates of morbidity, mortality, and increased healthcare costs, especially when a patient requires repeat operative interventions. Many groups have studied the mechanisms driving post-surgical adhesion formation. Despite continued advancements, we are yet to identify a prevailing mechanism. It is highly likely that post-operative adhesions have a multifactorial etiology. This complex pathophysiology, coupled with our incomplete understanding of the underlying pathways, has resulted in therapeutic options that have failed to demonstrate safety and efficacy on a consistent basis. The translation of findings from basic and preclinical research into robust clinical trials has also remained elusive. Herein, we present and contextualize the latest findings surrounding mechanisms that have been implicated in post-surgical adhesion formation.
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Affiliation(s)
- Ali Fatehi Hassanabad
- Section of Cardiac Surgery, Department of Cardiac Sciences, Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 2N9, Canada; (A.F.H.); (A.N.Z.); (J.F.D.)
| | - Anna N. Zarzycki
- Section of Cardiac Surgery, Department of Cardiac Sciences, Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 2N9, Canada; (A.F.H.); (A.N.Z.); (J.F.D.)
| | - Kristina Jeon
- Department of Anesthesiology and Pain Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G 2R7, Canada;
| | - Justin F. Deniset
- Section of Cardiac Surgery, Department of Cardiac Sciences, Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 2N9, Canada; (A.F.H.); (A.N.Z.); (J.F.D.)
- Department of Physiology and Pharmacology, University of Calgary, Calgary, AB T2N 1N4, Canada
| | - Paul W. M. Fedak
- Section of Cardiac Surgery, Department of Cardiac Sciences, Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 2N9, Canada; (A.F.H.); (A.N.Z.); (J.F.D.)
- Correspondence:
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Fatehi Hassanabad A, Zarzycki AN, Jeon K, Dundas JA, Vasanthan V, Deniset JF, Fedak PWM. Prevention of Post-Operative Adhesions: A Comprehensive Review of Present and Emerging Strategies. Biomolecules 2021; 11:biom11071027. [PMID: 34356652 PMCID: PMC8301806 DOI: 10.3390/biom11071027] [Citation(s) in RCA: 66] [Impact Index Per Article: 16.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2021] [Revised: 07/06/2021] [Accepted: 07/07/2021] [Indexed: 02/06/2023] Open
Abstract
Post-operative adhesions affect patients undergoing all types of surgeries. They are associated with serious complications, including higher risk of morbidity and mortality. Given increased hospitalization, longer operative times, and longer length of hospital stay, post-surgical adhesions also pose a great financial burden. Although our knowledge of some of the underlying mechanisms driving adhesion formation has significantly improved over the past two decades, literature has yet to fully explain the pathogenesis and etiology of post-surgical adhesions. As a result, finding an ideal preventative strategy and leveraging appropriate tissue engineering strategies has proven to be difficult. Different products have been developed and enjoyed various levels of success along the translational tissue engineering research spectrum, but their clinical translation has been limited. Herein, we comprehensively review the agents and products that have been developed to mitigate post-operative adhesion formation. We also assess emerging strategies that aid in facilitating precision and personalized medicine to improve outcomes for patients and our healthcare system.
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Affiliation(s)
- Ali Fatehi Hassanabad
- Section of Cardiac Surgery, Department of Cardiac Sciences, Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 2N9, Canada; (A.F.H.); (A.N.Z.); (J.A.D.); (V.V.); (J.F.D.)
| | - Anna N. Zarzycki
- Section of Cardiac Surgery, Department of Cardiac Sciences, Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 2N9, Canada; (A.F.H.); (A.N.Z.); (J.A.D.); (V.V.); (J.F.D.)
| | - Kristina Jeon
- Department of Anesthesiology and Pain Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G 2R7, Canada;
| | - Jameson A. Dundas
- Section of Cardiac Surgery, Department of Cardiac Sciences, Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 2N9, Canada; (A.F.H.); (A.N.Z.); (J.A.D.); (V.V.); (J.F.D.)
| | - Vishnu Vasanthan
- Section of Cardiac Surgery, Department of Cardiac Sciences, Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 2N9, Canada; (A.F.H.); (A.N.Z.); (J.A.D.); (V.V.); (J.F.D.)
| | - Justin F. Deniset
- Section of Cardiac Surgery, Department of Cardiac Sciences, Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 2N9, Canada; (A.F.H.); (A.N.Z.); (J.A.D.); (V.V.); (J.F.D.)
- Department of Physiology and Pharmacology, University of Calgary, Calgary, AB T2N 1N4, Canada
| | - Paul W. M. Fedak
- Section of Cardiac Surgery, Department of Cardiac Sciences, Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 2N9, Canada; (A.F.H.); (A.N.Z.); (J.A.D.); (V.V.); (J.F.D.)
- Correspondence:
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Abstract
The development of adhesions after gynecologic surgery is a severe problem with ramifications that go beyond the medical complications patients suffer (which most often include pain, obstruction and infertility), since they also impose a huge financial burden on the health care system and increase the workload of surgeons and all personnel involved in surgical follow-up care. Surgical techniques to avoid adhesion formation have not proven to be sufficient and pharmaceutical approaches for their prevention are even less effective, which means that the use of adhesion prevention devices is essential for achieving decent prophylaxis. This review explores the wide range of adhesion prevention products currently available on the market. Particular emphasis is put on prospective randomized controlled clinical trials that include second-look interventions, as these offer the most solid evidence of efficacy. We focused on adhesion scores, which are the most common way to quantify adhesion formation. This enables a direct comparison of the efficacies of different devices. While the greatest amount of data are available for oxidized regenerated cellulose, the outcomes with this adhesion barrier are mediocre and several studies have shown little efficacy. The best results have been achieved using adhesion barriers based on either modified starch, i.e., 4DryField® PH (PlantTec Medical GmbH, Lüneburg, Germany), or expanded polytetrafluoroethylene, i.e., GoreTex (W.L. Gore & Associates, Inc., Medical Products Division, Flagstaff, AZ), albeit the latter, as a non-resorbable barrier, has a huge disadvantage of having to be surgically removed again. Therefore, 4DryField® PH currently appears to be a promising approach and further studies are recommended.
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Shin CS, Cabrera FJ, Lee R, Kim J, Ammassam Veettil R, Zaheer M, Adumbumkulath A, Mhatre K, Ajayan PM, Curley SA, Scott BG, Acharya G. 3D-Bioprinted Inflammation Modulating Polymer Scaffolds for Soft Tissue Repair. ADVANCED MATERIALS (DEERFIELD BEACH, FLA.) 2021; 33:e2003778. [PMID: 33325594 DOI: 10.1002/adma.202003778] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/02/2020] [Revised: 11/14/2020] [Indexed: 06/12/2023]
Abstract
Development of inflammation modulating polymer scaffolds for soft tissue repair with minimal postsurgical complications is a compelling clinical need. However, the current standard of care soft tissue repair meshes for hernia repair is highly inflammatory and initiates a dysregulated inflammatory process causing visceral adhesions and postsurgical complications. Herein, the development of an inflammation modulating biomaterial scaffold (bioscaffold) for soft tissue repair is presented. The bioscaffold design is based on the idea that, if the excess proinflammatory cytokines are sequestered from the site of injury by the surgical implantation of a bioscaffold, the inflammatory response can be modulated, and the visceral adhesion formations and postsurgical complications can be minimized. The bioscaffold is fabricated by 3D-bioprinting of an in situ phosphate crosslinked poly(vinyl alcohol) polymer. In vivo efficacy of the bioscaffold is evaluated in a rat ventral hernia model. In vivo proinflammatory cytokine expression analysis and histopathological analysis of the tissues have confirmed that the bioscaffold acts as an inflammation trap and captures the proinflammatory cytokines secreted at the implant site and effectively modulates the local inflammation without the need for exogenous anti-inflammatory agents. The bioscaffold is very effective in inhibiting visceral adhesions formation and minimizing postsurgical complications.
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Affiliation(s)
- Crystal S Shin
- Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX, 77030, USA
| | - Fernando J Cabrera
- Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX, 77030, USA
| | - Richard Lee
- Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX, 77030, USA
| | - John Kim
- Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX, 77030, USA
| | - Remya Ammassam Veettil
- Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX, 77030, USA
| | - Mahira Zaheer
- Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX, 77030, USA
| | - Aparna Adumbumkulath
- Department of Materials Science and Nanoengineering, Rice University, Houston, TX, 77030, USA
| | - Kirti Mhatre
- Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX, 77030, USA
| | - Pulickel M Ajayan
- Department of Materials Science and Nanoengineering, Rice University, Houston, TX, 77030, USA
| | - Steven A Curley
- Oncology Institute, Christus Health Institute, 910 East Houston St., Suite 270, Tyler, TX, 75702, USA
| | - Bradford G Scott
- Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX, 77030, USA
| | - Ghanashyam Acharya
- Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX, 77030, USA
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15
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Postoperative peritoneal adhesion: an update on physiopathology and novel traditional herbal and modern medical therapeutics. Naunyn Schmiedebergs Arch Pharmacol 2020; 394:317-336. [PMID: 32979062 DOI: 10.1007/s00210-020-01961-8] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2020] [Accepted: 08/06/2020] [Indexed: 02/06/2023]
Abstract
Postoperative peritoneal adhesion (PPA) is a serious clinical condition that affects the high percentage of patients after abdominal surgery. In this review, we have tried to focus on pathophysiology and different underlying signal pathways of adhesion formation based on recent progress in the molecular and cellular mechanisms. Also, the strategies, developed based on traditional herbal and modern medicines, to prevent and treat the PPA via regulation of the molecular mechanisms were investigated. The search engines such as Google Scholar, PubMed, Scopus, and Science Direct have been used to evaluate the current literature related to the pathogenesis of adhesion formation and novel products. Recently, different mechanisms have been defined for adhesion formation, mainly categorized in fibrin formation and adhesion fibroblast function, inflammation, and angiogenesis. Therefore, the suppression of these mechanisms via traditional and modern medicine has been suggested in several studies. While different strategies with encouraging findings have been developed, most of the studies showed contradictory results and were performed on animals. The herbal products have been introduced as safe and effective agent which can be considered in future preclinical and clinical studies. Although a wide range of therapeutics based on traditional and modern medicines have been suggested, there is no agreement in the efficacy of these methods to prevent or treat adhesion formation after surgeries. Further basic and clinical researches are still needed to propose the efficiency of recommended strategies for prevention and treatment of PPA.
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Rice AD, Patterson K, Reed ED, Wurn BF, Robles K, Klingenberg B, Weinstock LB, Pratt JSA, King CR, Wurn LJ. Decreasing recurrent bowel obstructions, improving quality of life with physiotherapy: Controlled study. World J Gastroenterol 2018; 24:2108-2119. [PMID: 29785079 PMCID: PMC5960816 DOI: 10.3748/wjg.v24.i19.2108] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2018] [Revised: 05/03/2018] [Accepted: 05/05/2018] [Indexed: 02/06/2023] Open
Abstract
AIM To compare (1) quality of life and (2) rate of recurrent small bowel obstructions (SBO) for patients treated with novel manual physiotherapy vs no treatment.
METHODS One hundred and three subjects (age 19-89) with a history of recurrent adhesive SBO were treated with a manual physiotherapy called the Clear Passage Approach (CPA) which focused on decreasing adhesive crosslinking in abdominopelvic viscera. Pre- and post-therapy data measured recurring obstructions and quality of life, using a validated test sent 90 d after therapy. Results were compared to 136 untreated control subjects who underwent the same measurements for subjects who did not receive any therapy, which is the normal course for patients with recurring SBO. Comparison of the groups allowed us to assess changes when the physiotherapy was added as an adjunct treatment for patients with recurring SBO.
RESULTS Despite histories of more prior hospitalizations, obstructions, surgeries, and years impacted by bowel issues, the 103 CPA-treated subjects reported a significantly lower rate of repeat SBO than 136 untreated controls (total obstructions P = 0.0003; partial obstructions P = 0.0076). Subjects treated with the therapy demonstrated significant improvements in five of six total domains in the validated Small Bowel Obstruction Questionnaire (SBO-Q). Domains of diet, pain, gastrointestinal symptoms, quality of life (QOL) and pain severity when compared to post CPA treatment were significantly improved (P < 0.0001). The medication domain was not changed in the CPA treated group (P = 0.176).
CONCLUSION CPA physical therapy was effective for patients with adhesive SBO with significantly lower recurrence rate, improvement in reported symptoms and overall quality of life of subjects.
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Affiliation(s)
- Amanda D Rice
- Department of Internal Medicine, College of Medicine-Phoenix, University of Arizona, Phoenix, AZ 85004, United States
| | | | - Evette D Reed
- Clear Passage Therapies, Gainesville, FL 32606, United States
| | - Belinda F Wurn
- Clear Passage Therapies, Gainesville, FL 32606, United States
| | - Kristen Robles
- Clear Passage Therapies, Gainesville, FL 32606, United States
| | - Bernhard Klingenberg
- Department of Mathematics and Statistics, Williams College, Williamstown, MA 01267, United States
| | - Leonard B Weinstock
- Clinical Medicine and Surgery, Washington University School of Medicine, Specialists in Gastroenterology, LLC, St. Louis, MO 63141, United States
| | - Janey SA Pratt
- Department of Surgery, Stanford University School of Medicine, Palo Alto, CA 94035, United States
| | - C Richard King
- College of Medicine, University of Florida, Gainesville, FL 32607, United States
| | - Lawrence J Wurn
- Clear Passage Therapies, Gainesville, FL 32606, United States
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Hyoju SK, Morrison S, Gul S, Gharedaghi MH, Mussa M, Najibi M, Economopoulos KP, Hamarneh SR, Hodin RA. Intestinal alkaline phosphatase decreases intraperitoneal adhesion formation. J Surg Res 2017; 208:84-92. [DOI: 10.1016/j.jss.2016.09.006] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2016] [Revised: 08/24/2016] [Accepted: 09/01/2016] [Indexed: 02/08/2023]
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Treating Small Bowel Obstruction with a Manual Physical Therapy: A Prospective Efficacy Study. BIOMED RESEARCH INTERNATIONAL 2016; 2016:7610387. [PMID: 26989690 PMCID: PMC4775771 DOI: 10.1155/2016/7610387] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/20/2015] [Accepted: 01/21/2016] [Indexed: 02/06/2023]
Abstract
Small bowel obstructions (SBOs) caused by adhesions are a common, often life-threatening postsurgical complication with few treatment options available for patients. This study examines the efficacy of a manual physical therapy treatment regimen on the pain and quality of life of subjects with a history of bowel obstructions due to adhesions in a prospective, controlled survey based study. Changes in six domains of quality of life were measured via ratings reported before and after treatment using the validated Small Bowel Obstruction Questionnaire (SBO-Q). Improvements in the domains for pain (p = 0.0087), overall quality of life (p = 0.0016), and pain severity (p = 0.0006) were significant when average scores before treatment were compared with scores after treatment. The gastrointestinal symptoms (p = 0.0258) domain was marginally significant. There was no statistically significant improvement identified in the diet or medication domains in the SBO-Q for this population. Significant improvements in range of motion in the trunk (p ≤ 0.001), often limited by adhesions, were also observed for all measures. This study demonstrates in a small number of subjects that this manual physical therapy protocol is an effective treatment option for patients with adhesive small bowel obstructions as measured by subject reported symptoms and quality of life.
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Aznan MI, Khan OH, Unar AO, Tuan Sharif SE, Khan AH, Syed Abd. Aziz SH, Zakaria AD. Effect of Tualang honey on the anastomotic wound healing in large bowel anastomosis in rats-A randomized controlled trial. BMC COMPLEMENTARY AND ALTERNATIVE MEDICINE 2016; 16:28. [PMID: 26803744 PMCID: PMC4724403 DOI: 10.1186/s12906-016-1003-6] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/19/2015] [Accepted: 01/19/2016] [Indexed: 12/20/2022]
Abstract
BACKGROUND Honey has long been used for the treatment of number of ailments and diseases including surgical wounds. Current study evaluates the effectiveness of Tualang honey (TH) for large bowel anastomotic healing in Wistar rats. METHODS Thirty male Wistar rats were given a 3 centimeter infra-umbilical laparotomy wound, in`flicted on their abdomen. The colonic transection was performed at 5 cm distal to caecum, with end to end anastomosis of colon segment. They were divided into two groups. Group I was fed with standard rat chow and water. Meanwhile, Group II apart from standard feed, was also given TH 1.0 g/kg every morning until day seven post operatively. Afterwards, anastomotic bursting pressures were measured and histopathological examination on the anastomosis line was performed with light microscopes. The data from two groups were analyzed by Independent paired t test for continuous variables. RESULTS It was found that the tensile strength of colon anastomosis (95 % CI; p = <0.001) and the histopathological study including fibroblast count (p = <0.001) and inflammatory cells (p = 0.002) showed statistically significant difference in the favor of TH-treated group. Meanwhile, neovascularization formation was not statistically significant (p = 0.807); however, the overall count in the TH group was high. CONCLUSION Oral treatment with TH enhances anastomotic wound healing by increasing the number of fibroblasts and by decreasing inflammatory cells leading towards increased wound strength.
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Affiliation(s)
- Muhammad Izani Aznan
- Department of Surgery, School of Medical Sciences, Universiti Sains Malaysia, Health Campus, Kota Bharu, 16150 Malaysia
| | - Omaid Hayat Khan
- Discipline of Clinical Pharmacy, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang, 11800 Malaysia
| | - Allah Obhayo Unar
- Department of Surgery, School of Medical Sciences, Universiti Sains Malaysia, Health Campus, Kota Bharu, 16150 Malaysia
| | - Sharifah Emilia Tuan Sharif
- Department of Histopathology, School of Medical Sciences, Universiti Sains Malaysia, Health Campus, Kota Bharu, 16150 Malaysia
| | - Amer Hayat Khan
- Discipline of Clinical Pharmacy, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang, 11800 Malaysia
| | - Syed Hassan Syed Abd. Aziz
- Department of Surgery, School of Medical Sciences, Universiti Sains Malaysia, Health Campus, Kota Bharu, 16150 Malaysia
| | - Andee Dzulkarnaen Zakaria
- Department of Surgery, School of Medical Sciences, Universiti Sains Malaysia, Health Campus, Kota Bharu, 16150 Malaysia
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Nikeghbalian S, Vafaei H, Moradian F, Kazemi K, Tanideh N, Shayan L, Nikeghbalian Z. Administration of Intravenous Inf liximab for Prevention of Peritoneal Adhesions Formation in Rats. Bull Emerg Trauma 2015; 3:97-103. [PMID: 27162911 PMCID: PMC4771249] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2015] [Revised: 04/18/2015] [Accepted: 06/03/2015] [Indexed: 06/05/2023] Open
Abstract
OBJECTIVES To investigate the effects of intravenous infliximab in preventing the formation of peritoneal adhesions in an animal model of rat. METHODS This was an experimental study being performed in animal laboratory of Shiraz University of Medical Sciences during 2012. Sixty albino rats were randomly assigned in to three groups by Random Design Method. The first group received single infliximab injection (n=20), the second one received double infliximab injection (n=20) and the third received nothing (n=20), after receiving intra-peritoneal injection of talc for induction of peritoneal adhesions. All the animals were sacrificed after 6 weeks and the peritoneal adhesions were evaluated according to Nair classification. RESULTS We observed that the mean adhesion grade was lower in those who received double dose of infliximib when compared to single dose and controls. However the difference did not reach a significant value (p=0.178). The grade of peritoneal adhesion was also comparable between the three study groups (p=0.103). The mean number of 1st WBC count was also comparable between three study groups (p=0.382). We observed that 2nd WBC count was also comparable between two study groups (p=0.317). CONCLUSION Administration of intravenous infliximab after intraabdominal surgicalprocedures would not prevent the formation of peritoneal adhesions in animal model of albino rat.
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Affiliation(s)
- Saman Nikeghbalian
- Department of Transplantation, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Homeira Vafaei
- Department of Obstetrics and Gynecology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Farid Moradian
- Trauma Research Center, Shahid Rajaee (Emtiaz) Trauma Hospital, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Kourosh Kazemi
- Animal Laboratory, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Nader Tanideh
- Animal Laboratory, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Leila Shayan
- Trauma Research Center, Shahid Rajaee (Emtiaz) Trauma Hospital, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Zahra Nikeghbalian
- Department of Anesthesiology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
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Beyene RT, Kavalukas SL, Barbul A. Intra-abdominal adhesions: Anatomy, physiology, pathophysiology, and treatment. Curr Probl Surg 2015; 52:271-319. [PMID: 26258583 DOI: 10.1067/j.cpsurg.2015.05.001] [Citation(s) in RCA: 73] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2015] [Accepted: 05/12/2015] [Indexed: 12/18/2022]
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Mynbaev OA, Eliseeva MY, Tinelli A, Malvasi A, Kosmas IP, Medvediev MV, Babenko TI, Mazitova MI, Kalzhanov ZR, Stark M. A personalized adhesion prevention strategy: E. Arslan, T. Talih, B. Oz, B. Halaclar, K. Caglayan, M. Sipahi, Comparison of lovastatin and hyaluronic acid/carboxymethyl cellulose on experimental created peritoneal adhesion model in rats, Int. J. Surg. 12 (2) (2014) 120-124. Int J Surg 2014; 12:901-5. [PMID: 25072704 DOI: 10.1016/j.ijsu.2014.03.022] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2014] [Revised: 03/02/2014] [Accepted: 03/14/2014] [Indexed: 11/26/2022]
Affiliation(s)
- O A Mynbaev
- The International Translational Medicine & Biomodeling Research Team, Department of Applied Mathematics, Moscow Institute of Physics & Technology (State University), Dolgoprudny, Moscow Region, Russia; The Department of Obstetrics, Gynecology & Reproductive Medicine, Peoples' Friendship, University of Russia, Moscow, Russia; Laboratory of Pilot Projects, Moscow State University of Medicine & Dentistry, Moscow, Russia; The New European Surgical Academy, Berlin, Germany.
| | - M Yu Eliseeva
- The Department of Obstetrics, Gynecology & Reproductive Medicine, Peoples' Friendship, University of Russia, Moscow, Russia
| | - A Tinelli
- Department of Obstetrics and Gynaecology, Division of Experimental Endoscopic Surgery, Imaging, Minimally Invasive Therapy and Technology, Vito Fazzi Hospital, Piazza Muratore, Lecce, Italy
| | - A Malvasi
- Department of Obstetrics and Gynecology, Santa Maria Hospital, Bari, Italy
| | - I P Kosmas
- Xatzikosta General Hospital, Ioannina, Ioannina, Greece
| | - M V Medvediev
- State Establishment "Dnepropetrovsk Medical Academy of Health Ministry of Ukraine", Dnepropetrovsk, Ukraine
| | - T I Babenko
- Stavropol State Medical Academy, Stavropol, Russia
| | | | - Zh R Kalzhanov
- School of Health and Human Sciences, University of Essex, UK
| | - M Stark
- The New European Surgical Academy, Berlin, Germany
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Karanlik H, Kurt A, Kunduz E, Serin K, Saglam S, Soydinc HO, Yasasever V, Olgac V, Asoglu O. Effects of intraperitoneal bevacizumab administration on colonic anastomosis and early postoperative adhesion formation. Surg Innov 2013; 20:559-565. [PMID: 23487032 DOI: 10.1177/1553350613480855] [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] [Indexed: 02/01/2023]
Abstract
AIM The purpose of this study is to investigate the effect of intraperitoneal (IP) bevacizumab on colonic anastomosis and evaluate the effects on early postoperative adhesion formation. MATERIALS AND METHODS A total of 24 mature female Sprague-Dawley rats were used for this study. Rats were randomly assigned to a control group that received saline (n = 8) or to experimental groups (n = 8 each) that received bevacizumab at a dose of 2.5 mg/kg (group 1) or 5 mg/kg (group 2). Animals were killed humanely on the seventh day after operation, and measurements of anastomotic strength and biochemical variables were performed. RESULTS The mean adhesion grade was 2.63 ± 0.92, and 1 ± 0.93 and 0.75 ± 0.71 for the control and test groups, respectively. Bevacizumab significantly reduced adhesion formation in both low-dose and high-dose IP applications (P < .05). When all groups were compared, it was found that VEGF levels decreased significantly only in the tissue (P = .001), whereas there was no significant difference in the blood and the IP fluid (P = .73 and .08, respectively). We evaluated hydroxyproline levels, anastomosis bursting pressure, and histopathological healing scores. When each of these parameters were examined, there was statistical difference between groups (P = .01, .004, and .01, respectively). It was found that these parameters significantly decreased depending on increasing drug dose. CONCLUSION IP administration of bevacizumab effectively reduced the formation of adhesions and caused significant impairment of anastomotic wound healing when standard doses were administered (5 mg/kg), but the 2.5-mg/kg dosage did not affect the anastomotic wound healing and also effectively reduced the formation of adhesions.
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Affiliation(s)
- Hasan Karanlik
- 1Istanbul University Institute of Oncology, Istanbul, Turkey
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Gómez-Gil V, Pascual G, Pérez-Köhler B, Cifuentes A, Buján J, Bellón JM. Involvement of transforming growth factor-β3 and betaglycan in the cytoarchitecture of postoperative omental adhesions. J Surg Res 2013; 187:699-711. [PMID: 24332552 DOI: 10.1016/j.jss.2013.11.006] [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: 09/05/2013] [Revised: 11/06/2013] [Accepted: 11/07/2013] [Indexed: 01/03/2023]
Abstract
BACKGROUND Adhesions commonly appear in patients after abdominal surgery, with considerable individual variation in adhesion composition and severity of the repair process. Here, we address the influence of transforming growth factor (TGF)-β3 and betaglycan in this response, in relation to TGF-β1, in an adhesiogenic rabbit model. MATERIALS AND METHODS Omental adhesions were recovered 3, 7, 14, and 90 d after the implantation of a polypropylene mesh on the parietal peritoneum in New Zealand White rabbits. Omentum from nonoperated animals served as control. Tissue specimens were examined for TGF-β3 and TGF-β1 (Western blotting, reverse transcription-polymerase chain reaction), and TGF-β1:TGF-β3 messenger RNA and protein expression ratios were analyzed. Immunohistochemical detection of TGF-β3 and betaglycan was performed. RESULTS Injury to the omentum led to mobilization of TGF-β3 and betaglycan-expressing cells from milky spots. Fibrous zones in adhesions were simultaneous to the presence of TGF-β1 and the membrane-bound form of betaglycan (7-d adhesions), whereas soluble betaglycan appeared in TGF-β1-positive areas showing limited fibrosis (3-d adhesions). The elevated expression of TGF-β3 concurrent with the presence of membrane-bound form of betaglycan was observed in zones of adipose regeneration (14-d adhesions), whereas zones of fibrous consistency were negative for TGF-β3. CONCLUSIONS Milky spots on the omentum contain inflammatory/immune cells positive for TGF-β3, TGF-β1, and betaglycan, playing a role in the damaged omentum repair. Our observations support the contribution of TGF-β3 to tissue repair through adipose tissue regeneration and the profibrotic role of TGF-β1 and suggest that these effects on the local wound repair response could be driven by the expression of betaglycan in its soluble or membrane-bound form.
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Affiliation(s)
- Verónica Gómez-Gil
- Department of Medicine and Medical Specialties, Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Faculty of Medicine and Health Sciences, University of Alcalá, Alcalá de Henares, Madrid, Spain
| | - Gemma Pascual
- Department of Medicine and Medical Specialties, Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Faculty of Medicine and Health Sciences, University of Alcalá, Alcalá de Henares, Madrid, Spain
| | - Bárbara Pérez-Köhler
- Department of Surgery, Medical and Social Sciences, Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Faculty of Medicine and Health Sciences, University of Alcalá, Alcalá de Henares, Madrid, Spain
| | - Alberto Cifuentes
- Department of Medicine and Medical Specialties, Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Faculty of Medicine and Health Sciences, University of Alcalá, Alcalá de Henares, Madrid, Spain
| | - Julia Buján
- Department of Medicine and Medical Specialties, Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Faculty of Medicine and Health Sciences, University of Alcalá, Alcalá de Henares, Madrid, Spain
| | - Juan M Bellón
- Department of Surgery, Medical and Social Sciences, Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Faculty of Medicine and Health Sciences, University of Alcalá, Alcalá de Henares, Madrid, Spain.
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Thoma C, Bachy V, Seaton P, Green NK, Greaves DR, Klavinskis L, Seymour LW, Morrison J. Adenovirus serotype 11 causes less long-term intraperitoneal inflammation than serotype 5: implications for ovarian cancer therapy. Virology 2013; 447:74-83. [PMID: 24210101 DOI: 10.1016/j.virol.2013.08.032] [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: 07/02/2013] [Revised: 07/29/2013] [Accepted: 08/27/2013] [Indexed: 12/14/2022]
Abstract
In a phase II/III clinical trial intraperitoneal (i.p.) administration of a group C adenovirus vector (Ad5) caused bowel adhesion formation, perforation and obstruction. However, we had found that i.p. group B, in contrast to group C adenoviruses, did not cause adhesions in nude BALB/c ovarian cancer models, prompting further investigation. Ex vivo, group B Ad11 caused lower inflammatory responses than Ad5 on BALB/c peritoneal macrophages. In vivo, i.p. Ad11 triggered short-term cytokine and cellular responses equal to Ad5 in both human CD46-positive and -negative mice. In contrast, in a long-term study of repeated i.p. administration, Ad11 caused no/mild, whereas Ad5 induced moderate/severe adhesions and substantial liver toxicity accompanied by elevated levels of IFNγ and VEGF and loss of i.p. macrophages, regardless of CD46 expression. It appears that, although i.p. Ad11 evokes immediate inflammation similar to Ad5, repeated administration of Ad11 is better tolerated and long-term fibrotic tissue remodelling is reduced.
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Affiliation(s)
- Clemens Thoma
- Nuffield Department of Obstetrics and Gynaecology, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, UK.
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Kawashima R, Kawamura YI, Oshio T, Mizutani N, Okada T, Kawamura YJ, Konishi F, Dohi T. Comprehensive analysis of chemokines and cytokines secreted in the peritoneal cavity during laparotomy. J Immunoassay Immunochem 2012; 33:291-301. [PMID: 22738652 PMCID: PMC3431549 DOI: 10.1080/15321819.2011.638409] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Abstract
We recently found that chemokine-driven peritoneal cell aggregation is the primary mechanism of postoperative adhesion in a mouse model. To investigate this in humans, paired samples of peritoneal lavage fluid were obtained from seven patients immediately after incision (preoperative) and before closure (postoperative), and were assayed for the presence of 27 cytokines and chemokines using multiplex beads assay. As a result, IL-6 and CCL5 showed the most striking increase during operation. Recombinant CCL5 or lavage fluid induced chemotaxis of human peripheral blood mononuclear cells. We propose that CCL5 is possibly involved in the mechanism of postoperative adhesion in humans.
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Affiliation(s)
- Rei Kawashima
- Department of Gastroenterology, Research Center for Hepatitis and Immunology, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan
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Patel S, Lutz JM, Panchagnula U, Bansal S. Anesthesia and perioperative management of colorectal surgical patients - A clinical review (Part 1). J Anaesthesiol Clin Pharmacol 2012; 28:162-71. [PMID: 22557737 PMCID: PMC3339719 DOI: 10.4103/0970-9185.94831] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023] Open
Abstract
Colorectal surgery is commonly performed for colorectal cancer and other pathology such as diverticular and inflammatory bowel disease. Despite significant advances, such as laparoscopic techniques and multidisciplinary recovery programs, morbidity and mortality remain high and vary among surgical centers. The use of scoring systems and assessment of functional capacity may help in identifying high-risk patients and predicting complications. An understanding of perioperative factors affecting colon blood flow and oxygenation, suppression of stress response, optimal fluid therapy, and multimodal pain management are essential. These fundamental principles are more important than any specific choice of anesthetic agents. Anesthesiologists can significantly contribute to enhance recovery and improve the quality of perioperative care.
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Affiliation(s)
- Santosh Patel
- Department of Anaesthesia, Consultant Anaesthetist, The Pennine Acute Hospitals NHS Trust, Rochdale, UK
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Wang N, Li Q, Zhang L, Lin H, Hu J, Li D, Shi S, Cui S, Zhou J, Ji J, Wan J, Cai G, Chen X. Mesenchymal stem cells attenuate peritoneal injury through secretion of TSG-6. PLoS One 2012; 7:e43768. [PMID: 22912904 PMCID: PMC3422344 DOI: 10.1371/journal.pone.0043768] [Citation(s) in RCA: 82] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2012] [Accepted: 07/24/2012] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Mesothelial cell injury plays an important role in peritoneal fibrosis. Present clinical therapies aimed at alleviating peritoneal fibrosis have been largely inadequate. Mesenchymal stem cells (MSCs) are efficient for repairing injuries and reducing fibrosis. This study was designed to investigate the effects of MSCs on injured mesothelial cells and peritoneal fibrosis. METHODOLOGY/PRINCIPAL FINDINGS Rat bone marrow-derived MSCs (5 × 10(6)) were injected into Sprague-Dawley (SD) rats via tail vein 24 h after peritoneal scraping. Distinct reductions in adhesion formation; infiltration of neutrophils, macrophage cells; number of fibroblasts; and level of transforming growth factor (TGF)-β1 were found in MSCs-treated rats. The proliferation and repair of peritoneal mesothelial cells in MSCs-treated rats were stimulated. Mechanically injured mesothelial cells co-cultured with MSCs in transwells showed distinct increases in migration and proliferation. In vivo imaging showed that MSCs injected intravenously mainly accumulated in the lungs which persisted for at least seven days. No apparent MSCs were observed in the injured peritoneum even when MSCs were injected intraperitoneally. The injection of serum-starved MSCs-conditioned medium (CM) intravenously reduced adhesions similar to MSCs. Antibody based protein array of MSCs-CM showed that the releasing of TNFα-stimulating gene (TSG)-6 increased most dramatically. Promotion of mesothelial cell repair and reduction of peritoneal adhesion were produced by the administration of recombinant mouse (rm) TSG-6, and were weakened by TSG-6-RNA interfering. CONCLUSIONS/SIGNIFICANCE Collectively, these results indicate that MSCs may attenuate peritoneal injury by repairing mesothelial cells, reducing inflammation and fibrosis. Rather than the engraftment, the secretion of TSG-6 by MSCs makes a major contribution to the therapeutic benefits of MSCs.
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Affiliation(s)
- Nan Wang
- State Key Laboratory of Kidney Diseases, Department of Nephrology, PLA General Hospital and Military Medical Postgraduate College, Beijing, China
- Medical College, NanKai University, Tianjin, China
| | - Qinggang Li
- State Key Laboratory of Kidney Diseases, Department of Nephrology, PLA General Hospital and Military Medical Postgraduate College, Beijing, China
| | - Li Zhang
- State Key Laboratory of Kidney Diseases, Department of Nephrology, PLA General Hospital and Military Medical Postgraduate College, Beijing, China
| | - Hongli Lin
- Department of Nephrology, the First Affiliated Hospital of Dalian Medical University, Liaoning, China
| | - Jie Hu
- State Key Laboratory of Kidney Diseases, Department of Nephrology, PLA General Hospital and Military Medical Postgraduate College, Beijing, China
| | - Diangeng Li
- State Key Laboratory of Kidney Diseases, Department of Nephrology, PLA General Hospital and Military Medical Postgraduate College, Beijing, China
| | - Suozhu Shi
- State Key Laboratory of Kidney Diseases, Department of Nephrology, PLA General Hospital and Military Medical Postgraduate College, Beijing, China
| | - Shaoyuan Cui
- State Key Laboratory of Kidney Diseases, Department of Nephrology, PLA General Hospital and Military Medical Postgraduate College, Beijing, China
| | - Jianhui Zhou
- State Key Laboratory of Kidney Diseases, Department of Nephrology, PLA General Hospital and Military Medical Postgraduate College, Beijing, China
| | - Jiayao Ji
- State Key Laboratory of Kidney Diseases, Department of Nephrology, PLA General Hospital and Military Medical Postgraduate College, Beijing, China
- Medical College, NanKai University, Tianjin, China
| | - Jiajia Wan
- State Key Laboratory of Kidney Diseases, Department of Nephrology, PLA General Hospital and Military Medical Postgraduate College, Beijing, China
- Medical College, NanKai University, Tianjin, China
| | - Guangyan Cai
- State Key Laboratory of Kidney Diseases, Department of Nephrology, PLA General Hospital and Military Medical Postgraduate College, Beijing, China
- * E-mail: (XC); (GC)
| | - Xiangmei Chen
- State Key Laboratory of Kidney Diseases, Department of Nephrology, PLA General Hospital and Military Medical Postgraduate College, Beijing, China
- * E-mail: (XC); (GC)
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Brochhausen C, Schmitt VH, Planck CNE, Rajab TK, Hollemann D, Tapprich C, Krämer B, Wallwiener C, Hierlemann H, Zehbe R, Planck H, Kirkpatrick CJ. Current strategies and future perspectives for intraperitoneal adhesion prevention. J Gastrointest Surg 2012; 16:1256-74. [PMID: 22297658 DOI: 10.1007/s11605-011-1819-9] [Citation(s) in RCA: 102] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2011] [Accepted: 12/28/2011] [Indexed: 01/31/2023]
Abstract
INTRODUCTION The formation of peritoneal adhesions still is a relevant clinical problem after abdominal surgery. Until today, the most important clinical strategies for adhesion prevention are accurate surgical technique and the physical separation of traumatized serosal areas. Despite a variety of barriers which are available in clinical use, the optimal material has not yet been found. DISCUSSION Mesothelial cells play a crucial physiological role in friction less gliding of the serosa and the maintenance of anantiadhesive surface. The formation of postoperative adhesions results from a cascade of events and is regulated by various cellular and humoral factors. Therefore, optimization or functionalization of barrier materials by developments interacting with this cascade on a structural or pharmacological level could give an innovative input for future strategies in peritoneal adhesion prevention. For this purpose, the proper understanding of the formal pathogenesis of adhesion formation is essential. Based on the physiology of the serosa and the pathophysiology of adhesion formation, the available barriers in current clinical practice as well as new innovations are discussed in the present review.
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Affiliation(s)
- Christoph Brochhausen
- REPAIR-lab, Institute of Pathology, University Medical Centre, Johannes Gutenberg-University, Langenbeckstraße 1,55101 Mainz, Germany.
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Maciver AH, McCall M, James Shapiro AM. Intra-abdominal adhesions: cellular mechanisms and strategies for prevention. Int J Surg 2011; 9:589-94. [PMID: 21964216 DOI: 10.1016/j.ijsu.2011.08.008] [Citation(s) in RCA: 102] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2011] [Accepted: 08/24/2011] [Indexed: 10/17/2022]
Abstract
Postoperative intra-abdominal adhesions represent a serious clinical problem. In this review, we have focused on recent progress in the cellular and humoral mechanisms underpinning adhesion formation, and have reviewed strategies that interfere with these pathways as a means to prevent their occurrence. Current and previous English-language literature on the pathogenesis of adhesion formation was identified. As the burden of surgical disease in the world population increases, and the frequency of reoperation increases, prevention of adhesion formation has become a pressing goal in surgical research.
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Affiliation(s)
- Allison H Maciver
- Department of Surgery, University of Alberta Hospitals, 2000 College Plaza, 8215 112th Street, Edmonton, Alberta, Canada T6G 2C8
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Basbug M, Bulbuller N, Camci C, Ayten R, Aygen E, Ozercan IH, Arikanoglu Z, Akbulut S. The effect of antivascular endothelial growth factor on the development of adhesion formation in laparotomized rats: experimental study. Gastroenterol Res Pract 2011; 2011:578691. [PMID: 21760775 PMCID: PMC3132490 DOI: 10.1155/2011/578691] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2011] [Accepted: 05/02/2011] [Indexed: 02/07/2023] Open
Abstract
Aims. This study determined the effects of a single dose of bevacizumab, an antiangiogenic recombinant monoclonal antibody that specifically targets vascular endothelial growth factor (VEGF), on adhesion formation in the rat cecal abrasion model. Methodology. Thirty female Wistar albino rats (200-224 g) were divided into three groups. All rats underwent laparotomy at which time cecal wall abrasion and abdominal wall injuries were induced. Group I (control) underwent only the abrasion procedure; Groups II and III received saline or bevacizumab intraperitoneally, respectively, following the abrasion. The rats were killed on postoperative day 7, and the severity of adhesions was evaluated, together with histopathological fibrosis parameters and immunohistochemical staining to identify the VEGF receptor. Results. The mean adhesion severity score in Groups I-III was 2.5 ± 0.52, 2.4 ± 0.69, and 0.7 ± 0.82, respectively; the score in Group III was significantly lower than that in Groups I (P < 0.001) and II (P < 0.001). In the histopathological evaluation, the mean fibrosis score in Group III was significantly lower that the scores in Groups I (P < 0.001) and II (P < 0.001). VEGF staining of the adhesion areas in Group III was significantly lower than that in Groups I (P < 0.001) and II (P < 0.001). Conclusion. Bevacizumab decreases adhesion formation following laparotomy in rats by blocking VEGF receptor occupancy.
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Affiliation(s)
- Murat Basbug
- Department of General Surgery, Diyarbakir Education and Research Hospital, 21400 Diyarbakir, Turkey
| | - Nurullah Bulbuller
- Department of General Surgery, Faculty of Medicine, Firat University, 23100 Elazig, Turkey
| | - Cemalettin Camci
- Department of General Surgery, Faculty of Medicine, Firat University, 23100 Elazig, Turkey
| | - Refik Ayten
- Department of General Surgery, Faculty of Medicine, Firat University, 23100 Elazig, Turkey
| | - Erhan Aygen
- Department of General Surgery, Faculty of Medicine, Firat University, 23100 Elazig, Turkey
| | - Ibrahim Hanifi Ozercan
- Department of Medical Pathology, Faculty of Medicine, Firat University, 23100 Elazig, Turkey
| | - Zulfu Arikanoglu
- Department of General Surgery, Diyarbakir Education and Research Hospital, 21400 Diyarbakir, Turkey
| | - Sami Akbulut
- Department of General Surgery, Diyarbakir Education and Research Hospital, 21400 Diyarbakir, Turkey
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Rizzo A, Spedicato M, Mutinati M, Minoia G, Angioni S, Jirillo F, Pantaleo M, Sciorsci RL. Peritoneal adhesions in human and veterinary medicine: from pathogenesis to therapy. A review. Immunopharmacol Immunotoxicol 2010; 32:481-94. [PMID: 20128633 DOI: 10.3109/08923970903524367] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
Any peritoneal inflammatory process consequent to infections or surgical injuries may induce abdominal adhesion formation. Peritoneal adhesions are connective laciniae that develop among abdomino-pelvic organs that limit physiologic visceral motion. Consequently, fertility may be impaired, and intestinal obstruction and pelvic pain may develop, mainly in subjects that had undergone gynaecological surgery. This review illustrates the pathogenic steps of adhesiogenesis and the therapeutic scenario that evolved over the years to tackle the threat of peritoneal adhesions, both in domestic animals and in women.
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Affiliation(s)
- Annalisa Rizzo
- Department of Animal Production, Faculty of Veterinary Medicine, University of Bari, Bari, Italy
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Ignjatovic D, Aasland K, Pettersen M, Sund S, Chen Y, Spasojevic M, Nesgaard JM. Intra-abdominal administration of bevacizumab diminishes intra-peritoneal adhesions. Am J Surg 2010; 200:270-5. [PMID: 20227057 DOI: 10.1016/j.amjsurg.2009.08.038] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2009] [Revised: 08/07/2009] [Accepted: 08/31/2009] [Indexed: 01/16/2023]
Abstract
AIM To determine the effect of a single dose of bevacizumab on adhesion formation in the rat cecum abrasion model. METHODS The cecum and parietal peritoneum of 38 male Wistar rats were abraded to promote adhesion formation. The rats were randomized into 2 groups: group 1 received bevacizumab (2.5 mg/kg) intraperitoneally, and group 2 received saline. On day 30 animals were killed, adhesions scored, and histopathological samples taken. RESULTS There was no wound dehiscence; there were 2 incision hernias (5.3%), 1 per group. Thirty-seven animals developed adhesions (97.4%). Adhesion grade and severity scores were significantly different between groups 1 and 2 at 2.7:1.6 (P = .018) and 3.8:2.7 (P = .007), respectively. There was no difference in adhesion square area (27.7:25.0%; P = .16), location (P = 1.00), or number (2.1:1.3; P = .06). Histopathology confirmed the statistical difference between groups (P = .049), and a highly significant correlation between results was shown (r = .758; P = .0001). CONCLUSION A single dose of intraperitoneal bevacizumab significantly reduces grade and severity of abdominal adhesions in the cecum abrasion rat model.
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Affiliation(s)
- Dejan Ignjatovic
- Department of Gastrointestinal Surgery, Vestfold Hospital, Tonsberg, Norway.
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Saber A. Effect of honey versus intergel in intraperitoneal adhesion prevention and colonic anastomotic healing: A randomized controlled study in rats. Int J Surg 2010; 8:121-7. [DOI: 10.1016/j.ijsu.2009.11.010] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2009] [Revised: 10/18/2009] [Accepted: 11/17/2009] [Indexed: 10/20/2022]
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Gómez-Gil V, García-Honduvilla N, Pascual G, Rodríguez M, Buján J, Bellón JM. Peritoneal adhesion formation and reformation tracked by sequential laparoscopy: optimizing the time point for adhesiolysis. Surgery 2009; 147:378-91. [PMID: 20004923 DOI: 10.1016/j.surg.2009.10.011] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2009] [Accepted: 10/05/2009] [Indexed: 11/19/2022]
Abstract
BACKGROUND In a high proportion of patients, operatively lysed adhesions reform. Using a rabbit adhesiogenesis model, this study assessed the efficacy of adhesiolysis and examined how this relates to the tissue composition of adhesions at the time of lysis. METHODS Polypropylene meshes (5 x 3.5 cm) were implanted on the parietal peritoneum of New Zealand white rabbits. Some animals were killed 3, 7, 14, and 90 days postimplantation to obtain adhesion tissue. Adhesion formation/reformation was monitored by sequential laparoscopy in other animals kept for 90 days and in a separate experimental group subjected to adhesiolysis at 3 days postimplantation. Immune and inflammatory response markers were determined by immunohistochemical, Western blotting, and real-time reverse transcriptase polymerase chain reaction procedures in adhesion tissue; areas occupied by adhesions were quantified in meshes. RESULTS In animals undergoing adhesiolysis, mesh areas covered by adhesions were significantly decreased at each follow-up time and affected areas became mesothelialized. Increased transforming growth factor (TGF)-beta1 expression was detected in adhesions at 3 days. Greatest TGF-beta1 and vascular endothelial growth factor (VEGF) protein expressions were observed at 7 days, whereas genetic overexpression was noted at 14 days. Active inflammatory cells peaked at the 7-day time point. CONCLUSION Adhesions formed at 3 days; at this critical time, an adhesiolysis was effective in preventing reformation of future adhesions. TGF-beta1 gene and protein expression were increased in 3-day adhesions with respect to the omentum. Levels of active TGF-beta1 and VEGF were increased at 7 days, along with the inflammatory response at this time point related to tissue remodeling, which led to stabilization of adhesions.
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Affiliation(s)
- Verónica Gómez-Gil
- Department of Medical Specialities, Faculty of Medicine, Networking Research Center on Bioengineering, Biomaterials and Nanomedicine, University of Alcalá, Alcalá de Henares, Madrid, Spain
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The omentum: anatomical, metabolic, and surgical aspects. J Gastrointest Surg 2009; 13:1138-46. [PMID: 19291335 DOI: 10.1007/s11605-009-0855-1] [Citation(s) in RCA: 75] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2009] [Accepted: 02/26/2009] [Indexed: 01/31/2023]
Abstract
INTRODUCTION The omentum is acknowledged to have diverse functions in the pathophysiology of intra-abdominal disease. Its angiogenic properties act as a natural defense mechanism in peritonitis and intra-abdominal sepsis. With advancing technology the omentum is revealing itself as a new player in the field of molecular surgery with special reference to cancer, obesity and tissue reconstruction. MATERIALS AND METHODS This article reviews the existing and potential surgical applications of the omentum.
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