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Ntampakis G, Pramateftakis MG, Anestiadou E, Bitsianis S, Ioannidis O, Bekiari C, Koliakos G, Karakota M, Tsakona A, Cheva A, Angelopoulos S. Experimental models of high-risk bowel anastomosis in rats: A systematic review. World J Exp Med 2024; 14:94135. [PMID: 38948424 PMCID: PMC11212746 DOI: 10.5493/wjem.v14.i2.94135] [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: 03/12/2024] [Revised: 04/23/2024] [Accepted: 05/10/2024] [Indexed: 06/19/2024] Open
Abstract
BACKGROUND Anastomotic leaks remain one of the most dreaded complications in gastrointestinal surgery causing significant morbidity, that negatively affect the patients' quality of life. Experimental studies play an important role in understanding the pathophysiological background of anastomotic healing and there are still many fields that require further investigation. Knowledge drawn from these studies can lead to interventions or techniques that can reduce the risk of anastomotic leak in patients with high-risk features. Despite the advances in experimental protocols and techniques, designing a high-quality study is still challenging for the investigators as there is a plethora of different models used. AIM To review current state of the art for experimental protocols in high-risk anastomosis in rats. METHODS This systematic review was performed according to The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. To identify eligible studies, a comprehensive literature search was performed in the electronic databases PubMed (MEDLINE) and Scopus, covering the period from conception until 18 October 2023. RESULTS From our search strategy 102 studies were included and were categorized based on the mechanism used to create a high-risk anastomosis. Methods of assessing anastomotic healing were extracted and were individually appraised. CONCLUSION Anastomotic healing studies have evolved over the last decades, but the findings are yet to be translated into human studies. There is a need for high-quality, well-designed studies that will help to the better understanding of the pathophysiology of anastomotic healing and the effects of various interventions.
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Affiliation(s)
- Georgios Ntampakis
- 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
| | - Stefanos Bitsianis
- 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
| | - Chryssa Bekiari
- Laboratory of Anatomy and Histology, School of Veterinary Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece
- Experimental and Research Center, Papageorgiou General Hospital of Thessaloniki, Thessaloniki 56403, Greece
| | - George Koliakos
- Laboratory of Biochemistry, Faculty of Medicine, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece
| | - Maria Karakota
- Laboratory of Biochemistry, Faculty of Medicine, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece
| | - Anastasia Tsakona
- Department of Pathology, Faculty of Medicine, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece
| | - Angeliki Cheva
- Department of Pathology, Faculty of Medicine, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece
| | - Stamatios Angelopoulos
- Fourth Department of Surgery, Medical School, Aristotle University of Thessaloniki, Thessaloniki 57010, Greece
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Geropoulos G, Psarras K, Giannis D, Martzivanou EC, Papaioannou M, Kakos CD, Pavlidis ET, Symeonidis N, Koliakos G, Pavlidis TE. Platelet rich plasma effectiveness in bowel anastomoses: A systematic review. World J Gastrointest Surg 2021; 13:1736-1753. [PMID: 35070077 PMCID: PMC8727194 DOI: 10.4240/wjgs.v13.i12.1736] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2021] [Revised: 08/11/2021] [Accepted: 11/18/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Anastomotic leak constitutes a major problem in abdominal surgery. Technical insufficiency, topical or systemic factors contribute to disrupted healing of the performed bowel anastomosis and result in anastomosis leakage, with detrimental effects on patient postoperative outcomes. Despite the investigation of several factors and the invention of protective materials, the ideal agent to prevent anastomotic leaks is yet to be determined. AIM To study the effect of platelet rich plasma (PRP) on the healing of bowel anastomoses. METHODS A systematic literature search was performed in PubMed, EMBASE, and Scopus databases to identify studies investigating the effect of PRP application on bowel anastomosis. RESULTS Eighteen studies were eligible with a total population of 712 animals including rats (14 studies), rabbits (2 studies) and pigs (2 studies). No postoperative complications were reported following PRP application. Fourteen out of 18 studies reported a statistically significant higher anastomosis bursting pressure in PRP groups compared to control either in healthy animals or animal models with underlying condition or intervention, such as intraperitoneal chemotherapy or peritonitis. Similar results were reported by ten studies in terms of tissue hydroxyproline levels. One study reported significant increase in collagen deposition in PRP groups. PRP application resulted in significantly decreased inflammatory cell infiltration in the presence of peritonitis or intraperitoneal chemotherapy (6 studies). CONCLUSION The application of PRP is associated with improved bowel anastomosis outcomes, especially in animal models having an underlying condition affecting the normal healing process. PRP application seems to augment the normal healing process under these circumstances. However, further studies are needed to investigate the potential role of PRP on bowel anastomosis healing, especially in clinical settings.
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Affiliation(s)
- Georgios Geropoulos
- Department of General Surgery, University College London Hospitals, London NW1 2BU, United Kingdom
- Laboratory of Scientific Research and Experimental Surgery, 2nd Propedeutic Department of Surgery, School of Medicine, Aristotle University, Thessaloniki 54642, Greece
- Surgery Working Group, Society of Junior Doctors, Athens 15123, Greece
| | - Kyriakos Psarras
- Laboratory of Scientific Research and Experimental Surgery, 2nd Propedeutic Department of Surgery, School of Medicine, Aristotle University, Thessaloniki 54642, Greece
| | - Dimitrios Giannis
- Institute of Health Innovations and Outcomes Research, Feinstein Institutes for Medical Research, Manhasset, NY 11030, United States
| | - Eirini Chrysovalantou Martzivanou
- Laboratory of Scientific Research and Experimental Surgery, 2nd Propedeutic Department of Surgery, School of Medicine, Aristotle University, Thessaloniki 54642, Greece
| | - Maria Papaioannou
- Laboratory of Biological Chemistry, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece
| | | | - Efstathios Theodoros Pavlidis
- Laboratory of Scientific Research and Experimental Surgery, 2nd Propedeutic Department of Surgery, School of Medicine, Aristotle University, Thessaloniki 54642, Greece
| | - Nikolaos Symeonidis
- Laboratory of Scientific Research and Experimental Surgery, 2nd Propedeutic Department of Surgery, School of Medicine, Aristotle University, Thessaloniki 54642, Greece
| | - Georgios Koliakos
- Laboratory of Biological Chemistry, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece
| | - Theodoros Efstathios Pavlidis
- Laboratory of Scientific Research and Experimental Surgery, 2nd Propedeutic Department of Surgery, School of Medicine, Aristotle University, Thessaloniki 54642, Greece
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Boztug CY, Karaagac Akyol T, Benlice C, Koc MA, Doganay Erdogan B, Ozcebe OI, Kuzu MA, Akyol C. Platelet-rich plasma treatment improves postoperative recovery in patients with pilonidal sinus disease: a randomized controlled clinical trial. BMC Surg 2021; 21:373. [PMID: 34670534 PMCID: PMC8529773 DOI: 10.1186/s12893-021-01370-5] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2021] [Accepted: 10/11/2021] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND Pilonidal sinus is a common health problem. The current study aimed to compare the impact of autologous platelet-rich plasma (PRP) with that of minimally invasive techniques in terms of pain reduction, return to daily activities, quality of life, and duration of wound healing after open excision and secondary closure. METHODS Patients who were over 18 years old and had chronic PS disease between March 2018 and January 2019 were enrolled and randomly divided into three groups. Open surgery and moist dressings were applied to patients in group A. Open surgery followed by PRP application was performed on patients in group B. Group C underwent curettage of the sinus cavity followed by application of PRP. In this prospective randomized controlled study, patients completed questionnaires (including the Nottingham Health Profile (NHP), Short Form-36 (SF-36) and clinical information) before and after surgery. Demographics, preoperative characteristics, healing parameters, and quality-of-life scores were evaluated and calculated before and after surgery. RESULTS AND CONCLUSION The cavity volume and wound-healing time were compared among the groups on postoperative days 0, 2, 3, 4, and 21. Each patient was followed up throughout the process of wound healing, and follow-up was continued afterward to monitor the patients for recurrence. Due to the nature of the treatment that group C received, this group achieved shorter healing times and smaller cavity volume than the other groups. In contrast, the recovery time per unit of cavity volume was significantly faster in group B than in the other groups. Overall postoperative pain scores were significantly lower for both PRP groups (open surgery, group B; minimally invasive surgery, group C) than for group A (p < 0.001) and showed different time courses among the groups. In the treatment of PS disease, PRP application improves postoperative recovery in that it speeds patients' return to daily activities, reduces their pain scores and increases their quality of life. Trial registration The current study is registered on the public website ClinicalTrials.gov (ClinicalTrials.gov identifier number: NCT04697082; date: 05/01/2021).
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Affiliation(s)
- Can Yahya Boztug
- Department of Surgery, Ankara University Faculty of Medicine, Ankara, Turkey
| | - Tulay Karaagac Akyol
- Department of Hematology, Hacettepe University Faculty of Medicine, Ankara, Turkey
| | - Cigdem Benlice
- Department of Surgery, Ankara University Faculty of Medicine, Ankara, Turkey
| | - Mehmet Ali Koc
- Department of Surgery, Ankara University Faculty of Medicine, Ankara, Turkey
| | | | - Osman Ilhami Ozcebe
- Department of Hematology, Hacettepe University Faculty of Medicine, Ankara, Turkey
| | - Mehmet Ayhan Kuzu
- Department of Surgery, Ankara University Faculty of Medicine, Ankara, Turkey
| | - Cihangir Akyol
- Department of Surgery, Ankara University Faculty of Medicine, Ankara, Turkey.
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Preclinical In Vivo-Models to Investigate HIPEC; Current Methodologies and Challenges. Cancers (Basel) 2021; 13:cancers13143430. [PMID: 34298644 PMCID: PMC8303745 DOI: 10.3390/cancers13143430] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2021] [Revised: 07/01/2021] [Accepted: 07/06/2021] [Indexed: 12/23/2022] Open
Abstract
Simple Summary Efficacy of cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) depends on patient selection, tumor type, delivery technique, and treatment parameters such as temperature, carrier solution, type of drug, dosage, volume, and treatment duration. Preclinical research offers a powerful tool to investigate the impact of these parameters and to assists in designing potentially more effective treatment protocols and clinical trials. This study aims to review the objectives, methods, and clinical relevance of in vivo preclinical HIPEC studies found in the literature. In total, 60 articles were included in this study. The selected articles were screened on the HIPEC parameters. Recommendations are provided and possible pitfalls are discussed on the choice of type of animal and tumor model per stratified parameters and study goal. The guidelines presented in this paper can improve the clinical relevance and impact of future in vivo HIPEC experiments. Abstract Hyperthermic intraperitoneal chemotherapy (HIPEC) is a treatment modality for patients with peritoneal metastasis (PM) of various origins which aims for cure in combination with cytoreductive surgery (CRS). Efficacy of CRS-HIPEC depends on patient selection, tumor type, delivery technique, and treatment parameters such as temperature, carrier solution, type of drug, dosage, volume, and treatment duration. Preclinical research offers a powerful tool to investigate the impact of these parameters and to assist in designing potentially more effective treatment protocols and clinical trials. The different methodologies for peritoneal disease and HIPEC are variable. This study aims to review the objectives, methods, and clinical relevance of in vivo preclinical HIPEC studies found in the literature. In this review, recommendations are provided and possible pitfalls are discussed on the choice of type of animal and tumor model per stratified parameters and study goal. The guidelines presented in this paper can improve the clinical relevance and impact of future in vivo HIPEC experiments.
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Gorur M, Sozutek A, Irkorucu O, Karakaya B. The influence of platelet-rich plasma (PRP) on colonic anastomosis healing impaired by intraperitoneal 5-flourouracil application. An experimental study. Acta Cir Bras 2020; 35:e202000504. [PMID: 32638844 PMCID: PMC7341987 DOI: 10.1590/s0102-865020200050000004] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2020] [Revised: 03/21/2020] [Accepted: 04/22/2020] [Indexed: 12/18/2022] Open
Abstract
PURPOSE 5-flourourasil (5-FU) is commonly used for early intraperitoneal chemotherapy in colorectal or appendiceal cancer patients with peritoneal carcinomatosis. Due to its effect, anastomosis healing can be impaired and leads to anastomotic leakage. In this study, we aimed to investigate the potential healing effect of platelet-rich plasma (PRP) on colonic anastomosis impaired by intraperitoneal 5-flourouracil application. METHODS After ten rats were sacrificed for preparing PRP, forty Wistar-albino rats were subjected to colonic anastomosis, and randomly allocated into four groups including 10 rats each. According to receiving PRP and/or 5-FU application, the groups were formed as control (C), 5-FU without PRP (CT), anastomosis with PRP (C-PRP), and 5-FU with PRP (CT-PRP). CT and CT-PRP groups also received 5-FU intraperitoneally on postoperative day 1 (POD 1). All animals were euthanized on pod 7. The body weight change, anastomotic bursting pressure (ABP), tissue hydroxiprolin (TH) and histopathological examination of each group were analyzed. RESULTS 5-FU application significantly reduced ABP levels when compared with group C, C-PRP and CT-PRP (for each comparison, p<0,01). PRP application in CT-PRP group raised the measure of ABP up to the levels of C group. Although tissue hydroxyproline levels (THL) levels of CT-PRP group were found higher than CT group, it was not significant (p=0.112). Microscopically, comparing with CT group, PRP application significantly promoted the healing of colonic anastomosis subjected to 5-FU application by improving tissue edema, necrosis, submucosal bridging and collagen formation (p<0.05). Tissue healing in CT-PRP group was observed as good as the control groups. (C, C-PRP, p=0.181, p=0.134; respectively). CONCLUSION PRP administration on colonic anastomosis significantly promotes the healing process of anastomosis in rats receiving 5-FU. This result encourages further clinical use of PRP to reduce the frequency of AL in patients receiving EPIC.
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Affiliation(s)
- Mustafa Gorur
- MD, Department of General Surgery, University of Health Sciences Adana City Training and Research Hospital, Adana, Turkey. Analysis of data, technical procedures, manuscript preparation
| | - Alper Sozutek
- PhD, Associate Professor, Division of Gastroenterological Surgery, Department of General Surgery, University of Health Sciences Adana City Training and Research Hospital, Adana, Turkey. Technical procedures, design of the study, analysis of data, manuscript preparation
| | - Oktay Irkorucu
- PhD, Professor, Department of General Surgery, University of Health Sciences Adana City Training and Research Hospital, Adana, Turkey. Analysis of data, critical revision
| | - Burak Karakaya
- MD, Department of General Surgery, University of Health Sciences Adana City Training and Research Hospital, Adana, Turkey. Acquisition of data
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