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Lin Z, Ma X, Ji H, Hou Y, He X, Zhu X, Hu A. A nomogram for predicting early biliary complications in adult liver recipients of deceased donor grafts: Integrating artery resistive index and clinical risk factors. Surgery 2025; 182:109352. [PMID: 40209401 DOI: 10.1016/j.surg.2025.109352] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2024] [Revised: 02/21/2025] [Accepted: 03/14/2025] [Indexed: 04/12/2025]
Abstract
BACKGROUND This study aimed to identify predictors of biliary complications within 90 days after liver transplantation in adult recipients of deceased donor grafts. METHODS The study retrospectively analyzed adult patients who underwent liver transplantation from January 2016 to December 2021 using deceased donor grafts in our center. Patients were randomly divided into training and validation cohorts (7:3 ratio). A nomogram was developed using least absolute shrinkage and selection operator logistic regression for feature selection, followed by a 2-way stepwise approach in multivariate logistic regression. Model performance was assessed with the C-index, receiver operating characteristic area under the curve, calibration curves, and decision curve analysis. RESULTS A total of 757 patients were included, of whom 76 developed early biliary complications. Least absolute shrinkage and selection operator binary logistic analysis showed that postoperative day 1 arterial resistance index, acute rejection, acute-on-chronic liver failure, hepatic artery thrombosis, recipient body mass index, and donor age were independent predictors of biliary complications within 90 days. A nomogram was established on the basis of these factors. The C-index for the final nomogram was 0.822. The area under the curve in the training cohort was 0.837 (95% confidence interval, 0.780-0.893) and 0.771 (95% confidence interval, 0.677-0.865) in the validation cohort. Calibration curves demonstrated good agreement between predicted and actual outcomes. Decision curve analysis confirmed the clinical utility of the nomogram. CONCLUSION Low arterial resistance index (≤0.57) on the first postoperative day is a predictor of biliary complications within 90 days after liver transplantation in adult recipients of deceased donor grafts. The nomogram provides a practical tool for predicting complications and guiding clinical decisions.
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Affiliation(s)
- Zepeng Lin
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, China; Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, China
| | - Xue Ma
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, China; Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, China
| | - Haibin Ji
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, China; Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, China
| | - Yibo Hou
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, China; Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, China
| | - Xiaoshun He
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, China; Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, China
| | - Xiaofeng Zhu
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, China; Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, China
| | - Anbin Hu
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, China; Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, China.
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Walshaw J, Hugh K, Helliwell J, Burke J, Jayne D. Perianastomotic pH Monitoring for Early Detection of Anastomotic Leaks in Gastrointestinal Surgery: A Systematic Review of the Literature. Surg Innov 2025; 32:180-195. [PMID: 39773077 PMCID: PMC11894859 DOI: 10.1177/15533506241313168] [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: 01/11/2025]
Abstract
IntroductionAnastomotic leak (AL) represents a significant complication following gastrointestinal (GI) surgery, contributing to increased morbidity and mortality. pH monitoring has emerged as a potential diagnostic tool for the early detection of AL, but its effectiveness and clinical utility remain to be fully elucidated. This review aims to summarise the evidence regarding perianastomotic pH monitoring for AL detection.MethodsA systematic search of relevant databases was conducted to identify pre-clinical and clinical studies investigating pH monitoring for AL detection following GI surgery. Studies were screened by two independent reviewers based on predefined inclusion and exclusion criteria. Data were extracted and presented as a narrative synthesis.ResultsA total of 10 studies were included in the review, comprising animal studies (n = 2), and human studies in upper GI (n = 3) and colorectal (n = 5) patients. Consistent findings of lower pH values in patients with AL across various postoperative time points were demonstrated. There was diversity in the pH detection method, in addition to variable frequency and timing of pH monitoring. Four studies reported a shorter time for AL detection with pH monitoring vs conventional methods, although no statistical comparisons were used. No standard pH cut-off value for AL detection was identified.ConclusionpH monitoring shows potential as a diagnostic tool for the early detection of AL following GI surgery. While the existing evidence supports its potential utility, further research is required to establish standardised protocols and assess its clinical impact.
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Affiliation(s)
- Josephine Walshaw
- Leeds Institute of Medical Research, St James’s University Hospital, University of Leeds, Leeds, UK
| | - Katherine Hugh
- Leeds Institute of Medical Research, St James’s University Hospital, University of Leeds, Leeds, UK
| | - Jack Helliwell
- Leeds Institute of Medical Research, St James’s University Hospital, University of Leeds, Leeds, UK
| | - Joshua Burke
- Leeds Institute of Medical Research, St James’s University Hospital, University of Leeds, Leeds, UK
| | - David Jayne
- Leeds Institute of Medical Research, St James’s University Hospital, University of Leeds, Leeds, UK
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Liu B, Xu Y, Zhang X, Yin X, Zhang Z, Ren B, Zhou W, Liu S. Developing a predictive model for delayed healing of esophagojejunal anastomotic fistula following total gastrectomy based on imaging and clinical inflammatory-nutritional status. Clin Nutr ESPEN 2025; 66:169-178. [PMID: 39814262 DOI: 10.1016/j.clnesp.2025.01.027] [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] [Received: 09/09/2024] [Revised: 12/07/2024] [Accepted: 01/03/2025] [Indexed: 01/18/2025]
Abstract
BACKGROUND Esophagojejunal anastomotic fistula (EJF) following radical total gastrectomy is a severe perioperative complication in patients with gastric cancer, particularly as delayed fistula healing increases hospitalization costs and leads to poor prognosis. Numerous factors influence the occurrence and progression of EJF, with inflammation and nutritional status being significant contributors to perioperative complications. Therefore, this study aims to investigate the prediction of delayed EJF healing based on postoperative clinical and imaging-related inflammation-nutrition status. METHODS We retrospectively collected data on 315 cases of EJF following radical total gastrectomy for gastric cancer from two centers between 2015 and 2023 (training group: center one with 194 cases, validation group: center two with 121 cases). EJF was diagnosed based on clinical presentation, gastrointestinal imaging, or endoscopic findings. The healing time for EJF was defined as the period from diagnosis to the removal of the abdominal drainage tube, and patients were categorized into early healing and delayed healing groups based on the median healing time. Postoperative abdominal computed tomography(CT) scans and clinical characteristics at the time of EJF diagnosis were collected. Univariate and multivariable logistic regression analyses were performed on the training group data to construct a predictive model (nomogram). The model's performance in both the training and validation groups was evaluated using the area under the receiver operating characteristic (ROC) curve (AUC), calibration curves, and decision curve analysis (DCA). RESULT The mean healing time for EJF was 16 ± 7 days (median time: 12 days, range: 4-43 days). Postoperative systemic immune-inflammation index (SII) > 521 × 10ˆ9/L, controlling nutritional status score (CONUT) > 4, nutritional support method, visceral fat index (VFI) < 74.42 cm2/m2, and skeletal muscle index (SMI) < 41.25 cm2/m2 were associated with delayed EJF healing times. A comprehensive model was developed, in the validation group, the model demonstrated an AUC of 0.838 (95 % confidence interval (95 % CI): 0.763-0.912). The DCA and calibration curves indicated a strong predictive consistency and clinical utility of the model.
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Affiliation(s)
- Bo Liu
- The Affiliated Hospital of Qingdao University, Qingdao 266001, Shandong province, China; Department of General Surgery, Lanzhou University Second Hospital, Chengguan District, Cuiyingmen No.82, Lanzhou 730030, Gansu province, China; The Second Clinical Medical College, Lanzhou University, Chengguan District, Cuiyingmen No.82, Lanzhou 730030, Gansu province, China
| | - Yuan Xu
- The Second Clinical Medical College, Lanzhou University, Chengguan District, Cuiyingmen No.82, Lanzhou 730030, Gansu province, China; Department of Radiology, Lanzhou University Second Hospital, Chengguan District, Cuiyingmen No.82, Lanzhou 730030, Gansu province, China; Key Laboratory of Medical Imaging of Gansu Province, Cuiyingmen No.82, Lanzhou 730030, Gansu province, China
| | - Xijie Zhang
- The Affiliated Hospital of Qingdao University, Qingdao 266001, Shandong province, China; Department of General Surgery, Lanzhou University Second Hospital, Chengguan District, Cuiyingmen No.82, Lanzhou 730030, Gansu province, China
| | - Xiaojiao Yin
- The Affiliated Hospital of Qingdao University, Qingdao 266001, Shandong province, China
| | - Zhoujing Zhang
- The Affiliated Hospital of Qingdao University, Qingdao 266001, Shandong province, China
| | - Bo Ren
- Department of General Surgery, Lanzhou University Second Hospital, Chengguan District, Cuiyingmen No.82, Lanzhou 730030, Gansu province, China; The Second Clinical Medical College, Lanzhou University, Chengguan District, Cuiyingmen No.82, Lanzhou 730030, Gansu province, China
| | - Wence Zhou
- Department of General Surgery, Lanzhou University Second Hospital, Chengguan District, Cuiyingmen No.82, Lanzhou 730030, Gansu province, China; The Second Clinical Medical College, Lanzhou University, Chengguan District, Cuiyingmen No.82, Lanzhou 730030, Gansu province, China.
| | - Shuangyong Liu
- The Affiliated Hospital of Qingdao University, Qingdao 266001, Shandong province, China.
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Sengul H, Bantavi V, Gloeck L, Li Yim AYF, Leven P, Efferz P, Schneiker B, Lysson M, De Jonge WJ, Wehner S. Layer-specific molecular signatures of colon anastomotic healing and leakage in mice. Mol Med 2025; 31:124. [PMID: 40169980 PMCID: PMC11959837 DOI: 10.1186/s10020-025-01167-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2024] [Accepted: 03/12/2025] [Indexed: 04/03/2025] Open
Abstract
BACKGROUND Colon anastomotic leakage (CAL) is a postoperative complication originating from disturbed colon anastomotic healing (CAH). Wound healing involves several well-coordinated stages, which have not been comprehensively studied for CAH or CAL. This study aims to provide transcriptional profiles of different intestinal layers of anastomotic tissues throughout distinct healing stages and to identify CAL-related genes. METHODS Proximal colon anastomosis was constructed with 8 interrupted sutures in mice. Six hours, 24 h and 72 h after surgery, anastomotic complications were assessed. Transcriptional profiles of inner (mucosa and submucosa) and outer (muscularis externa) layer of the anastomotic and naive control tissues were analyzed with 3' bulk mRNA sequencing to identify the layer-specific healing and leakage pathways. Selective target genes differing between CAL and CAH were measured for their protein expression. RESULTS Our data indicate that the mucosa/submucosa and muscularis externa enter inflammation stage at 6 h, proliferation stage at 24 h and tissue remodeling stage at 72 h during CAH. We observed that transcription profiles of the mucosa/submucosa, but not the muscularis externa, differ between CAH and CAL. Particularly, genes related to extracellular remodeling (including Col18a1 and Col16a1) and wound healing (Pdpn and Timp1) showed lower expression in the mucosa/submucosa of CAL tissue compared to CAH. Conformingly, protein levels for collagens as well IL-34 were decreased in CAL, while the TGF-β-pseudo-receptor BAMBI was increased in CAL compared to CAH tissues. CONCLUSIONS Mucosa/submucosa and muscularis externa are mostly in synchronization during the inflammation, proliferation, and extracellular remodeling stages during CAH. Transcriptional profiles within the anastomotic mucosa/submucosa differ between CAH and CAL in genes related to extracellular modelling and wound healing, indicating that genes of these pathways may contribute to CAL.
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Affiliation(s)
- Hilal Sengul
- Department of Surgery, University Hospital of Bonn, 53105, Bonn, Germany
- Tytgat Institute for Liver and Intestinal Research, Amsterdam UMC - University of Amsterdam, 1105BK, Amsterdam, The Netherlands
- Amsterdam Gastroenterology, Endocrinology, and Metabolism, Amsterdam UMC - University of Amsterdam, 1105BK, Amsterdam, The Netherlands
| | - Vasiliki Bantavi
- Department of Surgery, University Hospital of Bonn, 53105, Bonn, Germany
- Tytgat Institute for Liver and Intestinal Research, Amsterdam UMC - University of Amsterdam, 1105BK, Amsterdam, The Netherlands
- Amsterdam Gastroenterology, Endocrinology, and Metabolism, Amsterdam UMC - University of Amsterdam, 1105BK, Amsterdam, The Netherlands
| | - Laura Gloeck
- Department of Surgery, University Hospital of Bonn, 53105, Bonn, Germany
| | - Andrew Y F Li Yim
- Tytgat Institute for Liver and Intestinal Research, Amsterdam UMC - University of Amsterdam, 1105BK, Amsterdam, The Netherlands
- Amsterdam Gastroenterology, Endocrinology, and Metabolism, Amsterdam UMC - University of Amsterdam, 1105BK, Amsterdam, The Netherlands
| | - Patrick Leven
- Department of Surgery, University Hospital of Bonn, 53105, Bonn, Germany
| | - Patrik Efferz
- Department of Surgery, University Hospital of Bonn, 53105, Bonn, Germany
| | - Bianca Schneiker
- Department of Surgery, University Hospital of Bonn, 53105, Bonn, Germany
| | - Mariola Lysson
- Department of Surgery, University Hospital of Bonn, 53105, Bonn, Germany
| | - Wouter J De Jonge
- Department of Surgery, University Hospital of Bonn, 53105, Bonn, Germany
- Tytgat Institute for Liver and Intestinal Research, Amsterdam UMC - University of Amsterdam, 1105BK, Amsterdam, The Netherlands
- Amsterdam Gastroenterology, Endocrinology, and Metabolism, Amsterdam UMC - University of Amsterdam, 1105BK, Amsterdam, The Netherlands
| | - Sven Wehner
- Department of Surgery, University Hospital of Bonn, 53105, Bonn, Germany.
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Soga K, Hayakawa F, Fujiwara T, Gyotoku Y, Kusano Y, Kobori I, Tamano M. Effectiveness of direct needle puncture for complete hepaticojejunostomy anastomotic stricture after pancreaticoduodenectomy (with video). DEN OPEN 2025; 5:e396. [PMID: 38939119 PMCID: PMC11208879 DOI: 10.1002/deo2.396] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 03/04/2024] [Revised: 05/13/2024] [Accepted: 06/03/2024] [Indexed: 06/29/2024]
Abstract
A 79-year-old Japanese woman, who had undergone pancreaticoduodenectomy 6 months prior to presentation owing to pancreatic cancer, complained of jaundice with high fever. Computed tomography revealed proximal bile duct dilatation with complete hepaticojejunostomy anastomotic stricture (HJAS). We performed a single-balloon endoscopy for biliary drainage. The presence of a scar-like feature surrounding the anastomosis was identified as the HJAS. White-light imaging during single-balloon endoscopy revealed that the HJAS contained a milky whitish area (MWA), suggesting that a membranous and fibrosis layer affected continuous inflammation around the center of the anastomosis (within a scar-like feature). Endoscopic dilatation was performed using an endoscopic injection needle, with the MWA used as an indicator. A 23-gauge endoscopic injection needle was used to penetrate the center of the blind lumen within the MWA, and a pinhole was created in the stricture. After confirming the position of the proximal bile duct using a contrast medium with the needle, an endoscopic guidewire with a cannula was inserted into the pinhole. A through-the-scope sequential balloon dilator was used to dilate the stricture, and a plastic stent was inserted into the proximal bile duct. This endoscopic intervention led to positive outcomes. In cases of complete HJAS occlusion, an endoscopic approach to the bile duct is difficult because the anastomotic opening of the HJAS is not visible. Thus, puncturing within the MWA, which can be used as a scar-like landmark within a complete membranous HJAS, is considered a useful endoscopic strategy.
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Affiliation(s)
- Koichi Soga
- Department of GastroenterologyDokkyo Medical University Saitama Medical CenterSaitamaJapan
| | - Fuki Hayakawa
- Department of GastroenterologyDokkyo Medical University Saitama Medical CenterSaitamaJapan
| | - Takeshi Fujiwara
- Department of GastroenterologyDokkyo Medical University Saitama Medical CenterSaitamaJapan
| | - Yoshinori Gyotoku
- Department of GastroenterologyDokkyo Medical University Saitama Medical CenterSaitamaJapan
| | - Yumi Kusano
- Department of GastroenterologyDokkyo Medical University Saitama Medical CenterSaitamaJapan
| | - Ikuhiro Kobori
- Department of GastroenterologyDokkyo Medical University Saitama Medical CenterSaitamaJapan
| | - Masaya Tamano
- Department of GastroenterologyDokkyo Medical University Saitama Medical CenterSaitamaJapan
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Khalid MU, Ali D, Wu JY, Lee H, Khan A. Impact and Measurement of Mechanical Tension in Bowel Anastomosis: A Scoping Review of the Current Literature. J Surg Res 2025; 308:161-173. [PMID: 40090052 DOI: 10.1016/j.jss.2025.02.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2024] [Revised: 01/13/2025] [Accepted: 02/10/2025] [Indexed: 03/18/2025]
Abstract
INTRODUCTION Creating a "tension-free anastomosis" is a fundamental principle in safe bowel surgery. This review aims to summarize the current literature regarding the measurement and impact of tension on bowel anastomoses. METHODS This scoping review was conducted using a systematic literature search in the PubMed, SCOPUS, and EMBASE databases. Data were synthesized in tables and summarized paragraphically, with studies assessed using the Newcastle-Ottawa scale. RESULTS Out of the 350 studies identified in the initial literature review, 25 were included in this study. Several studies indicated that anastomotic leak and tension are strongly associated, with the presence of tension making leaks up to 10 times more likely. However, no objective and clinically available methods exist to measure tension on bowel anastomosis in humans. Freedom from tension has traditionally been measured via surrogate measures of adequate bowel mobilization and subjective assessment by operating surgeons. Animal and cadaveric studies have been the frontier for objective measurement of wall tension. These studies use tensiometers to measure tension and automated machines or pulley and ratcheting systems to increase tension at specified intervals. However, these methods are universally destructive due to their design of measuring maximal tensile load and are not readily adaptable to the operating room. CONCLUSIONS The current literature does not address the objective measurement of bowel tension in live human subjects. Given the importance of tension, developing an objective, safe, intraoperative method to measure bowel wall tension would be a valuable surgical tool.
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Affiliation(s)
- Muhammad Usman Khalid
- Department of Neurological Surgery, Kentucky Neuroscience Institute, University of Kentucky, Lexington, Kentucky
| | - Danish Ali
- Section of Surgical Sciences, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Jie Ying Wu
- Department of Computer Science, Vanderbilt University, Nashville, Tennessee
| | - Hanjoo Lee
- Department of Surgery, Harbor-UCLA Medical Center, Torrance, California
| | - Aimal Khan
- Section of Surgical Sciences, Vanderbilt University Medical Center, Nashville, Tennessee.
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Weber MC, Clees Z, Buck A, Fischer A, Steffani M, Wilhelm D, Martignoni M, Friess H, Rinkevich Y, Neumann PA. Role of the serosa in intestinal anastomotic healing: insights from in-depth histological analysis of human and murine anastomoses. BJS Open 2024; 8:zrae108. [PMID: 39230923 PMCID: PMC11373408 DOI: 10.1093/bjsopen/zrae108] [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: 06/21/2024] [Accepted: 07/27/2024] [Indexed: 09/05/2024] Open
Abstract
BACKGROUND Anastomotic leakage following colorectal surgery remains a significant complication despite advances in surgical techniques. Recent findings on serosal injury repair in coelomic cavities, such as the peritoneum, challenge the current understanding of the cellular origins and mechanisms underlying intestinal anastomotic healing. Understanding the contribution of each layer of the intestinal wall during anastomotic healing is needed to find new therapeutic strategies to prevent anastomotic leakage. The aim of this experimental study was to investigate the role of the serosal layer of the intestinal wall in anastomotic healing. MATERIALS AND METHODS Comprehensive histologic analysis of human and murine anastomoses was performed to elucidate histologic changes in the different intestinal layers during anastomotic healing. In vivo staining of the extracellular matrix (ECM) in the serosal layer was performed using a fluorophore-conjugated N-hydroxysuccinimide-ester before anastomosis surgery in a murine model. RESULTS Histological examination of both human and murine anastomoses revealed that closure of the serosal layer occurred first during the healing process. In vivo serosal ECM staining demonstrated that a significant portion of the newly formed ECM within the anastomosis was indeed deposited onto the serosal layer. Furthermore, mesenchymal cells within the anastomotic scar were positive for mesothelial cell markers, podoplanin and Wilms tumour protein. CONCLUSIONS In this experimental study, the results suggest that serosal scar formation is an important mechanism for anastomotic integrity in intestinal anastomoses. Mesothelial cells may significantly contribute to scar formation during anastomotic healing through epithelial-to-mesenchymal transition, potentially suggesting a novel therapeutic target to prevent anastomotic leakage by enhancing physiological healing processes.
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Affiliation(s)
- Marie-Christin Weber
- Department of Surgery, Technical University of Munich, TUM School of Medicine and Health, Munich, Germany
| | - Zoé Clees
- Department of Surgery, Technical University of Munich, TUM School of Medicine and Health, Munich, Germany
| | - Annalisa Buck
- Department of Surgery, Technical University of Munich, TUM School of Medicine and Health, Munich, Germany
- Institute for Advanced Study, Technical University of Munich, Munich, Germany
| | - Adrian Fischer
- Institute of Regenerative Biology and Medicine, Helmholtz Munich, Munich, Germany
| | - Marcella Steffani
- Department of Surgery, Technical University of Munich, TUM School of Medicine and Health, Munich, Germany
| | - Dirk Wilhelm
- Department of Surgery, Technical University of Munich, TUM School of Medicine and Health, Munich, Germany
| | - Marc Martignoni
- Department of Surgery, Technical University of Munich, TUM School of Medicine and Health, Munich, Germany
| | - Helmut Friess
- Department of Surgery, Technical University of Munich, TUM School of Medicine and Health, Munich, Germany
| | - Yuval Rinkevich
- Institute of Regenerative Biology and Medicine, Helmholtz Munich, Munich, Germany
| | - Philipp-Alexander Neumann
- Department of Surgery, Technical University of Munich, TUM School of Medicine and Health, Munich, Germany
- Institute for Advanced Study, Technical University of Munich, Munich, Germany
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Sun Q, Yang Z, Xu R, Li R, Li Y, Wang F, Li Y. Smart responsive staple for dynamic promotion of anastomotic stoma healing. Bioact Mater 2024; 39:630-642. [PMID: 38883312 PMCID: PMC11180322 DOI: 10.1016/j.bioactmat.2024.04.021] [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: 03/28/2024] [Revised: 04/19/2024] [Accepted: 04/21/2024] [Indexed: 06/18/2024] Open
Abstract
The precise combination of conflicting biological properties through sophisticated structural and functional design to meet all the requirements of anastomotic healing is of great demand but remains challenging. Here, we develop a smart responsive anastomotic staple (Ti-OH-MC) by integrating porous titanium anastomotic staple with multifunctional polytannic acid/tannic acid coating. This design achieves dynamic sequential regulation of antibacterial, anti-inflammatory, and cell proliferation properties. During the inflammatory phase of the anastomotic stoma, our Ti-OH-MC can release tannic acid to provide antibacterial and anti-inflammatory properties, together with immune microenvironment regulation function. At the same time, as the healing progresses, the multifunctional coating gradually falls off to expose the porous structure of the titanium anastomotic staple, which promotes cell adhesion and proliferation during the later proliferative and remodeling phases. As a result, our Ti-OH-MC exceeds the properties of clinically used titanium anastomotic staple, and can effectively promote the healing. The staple's preparation strategy is simple and biocompatible, promising for industrialisation and clinical application. This work provides an effective anastomotic staple for anastomotic stoma healing and serve as a reference for the functional design and preparation of other types of titanium-based tissue repair materials.
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Affiliation(s)
- Qi Sun
- School of Medicine, South China University of Technology, Guangzhou, Guangdong, 510006, China
- Department of Gastrointestinal Surgery, Department of General Surgery, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, China
| | - Zifeng Yang
- Department of Gastrointestinal Surgery, Department of General Surgery, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, China
| | - Ruijun Xu
- School of Medicine, South China University of Technology, Guangzhou, Guangdong, 510006, China
- Department of Gastrointestinal Surgery, Department of General Surgery, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, China
| | - Renjie Li
- Department of Gastrointestinal Surgery, Department of General Surgery, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, China
| | - Yang Li
- Department of Gastrointestinal Surgery, Department of General Surgery, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, China
| | - Feng Wang
- Department of Gastrointestinal Surgery, Department of General Surgery, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, China
- Guangxi Key Laboratory of Green Chemical Materials and Safety Technology, Guangxi Engineering Research Center for New Chemical Materials and Safety Technology, College of Petroleum and Chemical Engineering, Beibu Gulf University, Qinzhou, 535011, China
| | - Yong Li
- School of Medicine, South China University of Technology, Guangzhou, Guangdong, 510006, China
- Department of Gastrointestinal Surgery, Department of General Surgery, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, China
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Hu Z, Mao L, Liu X, Xing X, Zhang L, Zhou Q, Song C. A novel discrete linkage-type electrode for radiofrequency-induced intestinal anastomosis. MINIM INVASIV THER 2024; 33:71-79. [PMID: 38219217 DOI: 10.1080/13645706.2023.2291439] [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] [Received: 01/17/2023] [Accepted: 11/15/2023] [Indexed: 01/16/2024]
Abstract
INTRODUCTION For decades, radiofrequency (RF)-induced tissue fusion has garnered great attention due to its potential to replace sutures and staples for anastomosis of tissue reconstruction. However, the complexities of achieving high bonding strength and reducing excessive thermal damage present substantial limitations of existing fusion devices. MATERIALS AND METHODS This study proposed a discrete linkage-type electrode to carry out ex vivo RF-induced intestinal anastomosis experiments. The anastomotic strength was examined by burst pressure and shear strength test. The degree of thermal damage was monitored through an infrared thermal imager. And the anastomotic stoma fused by the electrode was further investigated through histopathological and ultrastructural observation. RESULTS The burst pressure and shear strength of anastomotic tissue can reach 62.2 ± 3.08 mmHg and 8.73 ± 1.11N, respectively, when the pressure, power and duration are 995 kPa, 160 W and 13 s, and the thermal damage can be controlled within limits. Histopathological and ultrastructural observation indicate that an intact and fully fused stomas with collagenic crosslink can be formed. CONCLUSION The discrete linkage-type electrode presents favorable efficiency and security in RF-induced tissue fusion, and these results are informative to the design of electrosurgical medical devices with controllable pressure and energy delivery.
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Affiliation(s)
- Zhongxin Hu
- Shanghai Institute for Minimally Invasive Therapy, School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, China
| | - Lin Mao
- Shanghai Institute for Minimally Invasive Therapy, School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, China
| | - Xuyan Liu
- School of Mechanical Engineering, University of Shanghai for Science and Technology, Shanghai, China
| | - Xupo Xing
- Shanghai Institute for Minimally Invasive Therapy, School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, China
| | - Linying Zhang
- Shanghai Institute for Minimally Invasive Therapy, School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, China
| | - Quan Zhou
- Shanghai Institute for Minimally Invasive Therapy, School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, China
| | - Chengli Song
- Shanghai Institute for Minimally Invasive Therapy, School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, China
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10
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Yu X, Tang W, Bai C, Li R, Feng B, Wu J, Guo X, Chen H, Li M. A predictive model for intraabdominal infection after radical gastrectomy in elderly patients. Medicine (Baltimore) 2024; 103:e37489. [PMID: 38489739 PMCID: PMC10939676 DOI: 10.1097/md.0000000000037489] [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: 11/09/2023] [Revised: 02/08/2024] [Accepted: 02/13/2024] [Indexed: 03/17/2024] Open
Abstract
Gastric cancer (GC) is one of the most common malignant tumors worldwide and the fourth leading cause of cancer-related deaths, with a relatively high incidence among the elderly population. Surgical resection is the mainstay treatment for GC and is currently the only cure. However, the incidence of postoperative intraabdominal infections remains high and seriously affects the prognosis. This study aimed to explore the risk factors for intraabdominal infections after radical gastrectomy in elderly patients and to establish and validate a risk prediction model. We collected the clinical data of 322 GC patients, who underwent radical gastrectomy at the General Surgery Department of China Medical University Dandong Central Hospital from January 2016 to January 2023. The patients were divided into an infected group (n = 27) and a noninfected group (n = 295) according to whether intraabdominal infections occurred postoperatively. A nomogram risk prediction model for the occurrence of postoperative intraabdominal infections was developed. All patients were randomized into a training set (n = 225) and a validation set (n = 97) in a 7:3 ratio, and the model was internally validated. Of the 322 patients, 27 (8.3%) experienced postoperative intraabdominal infections. Single-factor analysis revealed associations of intraabdominal infection with body mass index, glucose, hemoglobin, albumin, and other factors. The multifactorial analysis confirmed that body mass index, glucose, hemoglobin, albumin, surgical duration, and bleeding volume were independent risk factors for intraabdominal infections. The nomogram constructed based on these factors demonstrated excellent performance in both the training and validation sets. A nomogram model was developed and validated to predict the risk of intraabdominal infection after radical gastrectomy. The model has a good predictive performance, which could help clinicians prevent the occurrence of intraabdominal infections after radical gastrectomy in elderly patients.
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Affiliation(s)
- Xiaohan Yu
- General Surgery Department, Dandong Central Hospital, China Medical University, Dandong, Liaoning, China
| | - Wanyun Tang
- Orthopedics Department, Dandong Central Hospital, China Medical University, Dandong, Liaoning, China
| | - Chenglin Bai
- General Surgery Department, Dandong Central Hospital, Jinzhou Medical University, Dandong, Liaoning, China
| | - Runzhuo Li
- Gastroenterology Department, Dandong Central Hospital, China Medical University, Dandong, Liaoning, China
| | - Bo Feng
- General Surgery Department, Dandong Central Hospital, China Medical University, Dandong, Liaoning, China
| | - Jinge Wu
- General Surgery Department, Dandong Central Hospital, China Medical University, Dandong, Liaoning, China
| | - Xianzhan Guo
- General Surgery Department, Dandong Central Hospital, China Medical University, Dandong, Liaoning, China
| | - Hong Chen
- General Surgery Department, Dandong Central Hospital, China Medical University, Dandong, Liaoning, China
| | - Meng Li
- General Surgery Department, Dandong Central Hospital, China Medical University, Dandong, Liaoning, China
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11
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Petersen LLK, Dursun MD, Madsen G, Le DQS, Möller S, Qvist N, Ellebæk MB. Poly-ϵ-caprolactone scaffold as staple-line reinforcement of rectal anastomosis: an experimental piglet study. BMC Gastroenterol 2024; 24:112. [PMID: 38491416 PMCID: PMC10943786 DOI: 10.1186/s12876-024-03202-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2023] [Accepted: 03/11/2024] [Indexed: 03/18/2024] Open
Abstract
PURPOSE Rectal anastomoses have a persisting high incidence of anastomotic leakage. This study aimed to assess whether the use of a poly-ϵ-caprolactone (PCL) scaffold as reinforcement of a circular stapled rectal anastomosis could increase tensile strength and improve healing compared to a control in a piglet model. METHOD Twenty weaned female piglets received a stapled rectal anastomosis and were randomised to either reinforcement with PCL scaffold (intervention) or no reinforcement (control). On postoperative day five the anastomosis was subjected to a tensile strength test followed by a histological examination to evaluate the wound healing according to the Verhofstad scoring. RESULTS The tensile strength test showed no significant difference between the two groups, but histological evaluation revealed significant impaired wound healing in the intervention group. CONCLUSION The incorporation of a PCL scaffold into a circular stapled rectal anastomosis did not increase anastomotic tensile strength in piglets and indicated an impaired histologically assessed wound healing.
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Affiliation(s)
- Laura Lovisa Køtlum Petersen
- Research Unit of Surgery, Odense University Hospital, Odense, Denmark
- University of Southern Denmark, Odense, Denmark
| | - Martin Dennis Dursun
- Research Unit of Surgery, Odense University Hospital, Odense, Denmark.
- University of Southern Denmark, Odense, Denmark.
| | - Gunvor Madsen
- Research Unit of Pathology, Odense University Hospital, Odense, Denmark
| | | | - Sören Möller
- Open Patient data Explorative Network, Department of Clinical Research, Odense University Hospital and Research unit OPEN, University of Southern Denmark, Odense, Denmark
| | - Niels Qvist
- Research Unit of Surgery, Odense University Hospital, Odense, Denmark
- University of Southern Denmark, Odense, Denmark
| | - Mark Bremholm Ellebæk
- Research Unit of Surgery, Odense University Hospital, Odense, Denmark
- University of Southern Denmark, Odense, Denmark
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12
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Huang PY, Tsai MC, Kiu KT, Yen MH, Chang TC. Collagen patch cover facilitates recovery of bowel function after laparoscopic colectomy. BMC Surg 2024; 24:66. [PMID: 38378522 PMCID: PMC10880318 DOI: 10.1186/s12893-024-02339-w] [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] [Received: 10/01/2023] [Accepted: 01/31/2024] [Indexed: 02/22/2024] Open
Abstract
BACKGROUND Numerous factors can influence bowel movement recovery and anastomotic healing in colorectal surgery, and poor healing can lead to severe complications and increased medical expenses. Collagen patch cover (CPC) is a promising biomaterial that has been demonstrated to be safe in animal models and has been successfully applied in various surgical procedures in humans. This study. METHODS A retrospective review of medical records from July 2020 to June 2022 was conducted to identify consecutive patients who underwent laparoscopic colectomy. Patients who received CPC at the anastomotic site were assigned to the collagen group, whereas those who did not receive CPC were assigned to the control group. RESULTS Data from 241 patients (collagen group, 109; control group, 132) were analyzed. Relative to the control group, the collagen group exhibited a faster recovery of bowel function, including an earlier onset of first flatus (2.93 days vs. 3.43 days, p < 0.01), first defecation (3.73 days vs. 4.18 days, p = 0.01), and oral intake (4.30 days vs. 4.68 days, p = 0.04). CPC use was also associated with lower use of postoperative intravenous analgesics. The complication rates in the two groups did not differ significantly. CONCLUSIONS CPCs can be safely and easily applied to the anastomotic site during laparoscopic colectomy, and can accelerate bowel movement recovery. Further studies on the effectiveness of CPCs in colorectal surgery involving larger sample sizes are required. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov registration number: NCT05831956 (26/04/2023).
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Affiliation(s)
- Pin-Yang Huang
- Department of General Medicine, Taipei Medical University Shuang-Ho Hospital, No. 291, Zhongzheng Road, Zhonghe District, New Taipei City, 235, Taiwan
| | - Meng-Che Tsai
- Department of General Medicine, Chiayi Chang Gung Memorial Hospital, Chiayi County, No. 291, Zhongzheng Road, Zhonghe District, New Taipei City, 235, Taiwan
| | - Kee-Thai Kiu
- Division of Colorectal Surgery, Department of Surgery, Taipei Medical University Shuang-Ho Hospital, No. 291, Zhongzheng Road, Zhonghe District, New Taipei City, 235, Taiwan
| | - Min-Hsuan Yen
- Division of Colorectal Surgery, Department of Surgery, Taipei Medical University Shuang-Ho Hospital, No. 291, Zhongzheng Road, Zhonghe District, New Taipei City, 235, Taiwan
| | - Tung-Cheng Chang
- Division of Colorectal Surgery, Department of Surgery, Taipei Medical University Shuang-Ho Hospital, No. 291, Zhongzheng Road, Zhonghe District, New Taipei City, 235, Taiwan.
- Division of Colorectal Surgery, Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, No. 291, Zhongzheng Road, Zhonghe District, New Taipei City, 235, Taiwan.
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13
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Zong W, Salich J, Kastl A, Kirsch J, Albenberg L, Bales C. Whole Foods Introduction Associated With Symptomatic Anastomotic Ulceration in Children With Short Bowel Syndrome. J Pediatr Gastroenterol Nutr 2023; 77:788-795. [PMID: 37705420 DOI: 10.1097/mpg.0000000000003942] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 09/15/2023]
Abstract
OBJECTIVES Anastomotic ulceration (AU) is a rare but life-threatening complication of pediatric short bowel syndrome (SBS). AUs may be challenging to detect and refractory to treatment. This study aimed to identify features associated with symptomatic bleeding AUs in children with SBS and factors that may impact resolution of bleeding. The relationship between dietary changes and symptomatic anastomotic hemorrhage was also explored. METHODS We conducted a retrospective chart review of 381 patients cared for in the Intestinal Rehabilitation Program at our center from 2013 to 2022. Patients with symptomatic AUs were identified based on at least 1 endoscopic procedure showing AUs and evidence of clinically significant gastrointestinal bleeding. We collected patient demographics, clinical characteristics, dietary history, radiologic imaging, and histopathology. We used descriptive statistics to identify patterns of presentation. RESULTS AUs were identified in 22 patients who were followed for a median duration of 2.9 years after anastomotic ulcer identification. AUs uniformly evolved years after the initial anastomosis (median 3.2 years). Characteristics included bowel stricture (4/22), small bowel-colon anastomosis (19/22), partial colectomy (17/22), and an increase in whole foods fraction (12/18). Bleeding resolved with operative intervention in the majority with anastomotic stricture (3/4). Recurrent bleeding was common in those without stricture (13/18). In a subset of patients without stricture, whole food reduction was associated with improvement or resolution of bleeding (5/6). CONCLUSIONS We observed a higher proportion of patients with AUs who responded to surgical intervention in the subset of children with definitive anastomotic strictures versus those without, suggesting that careful characterization of intestinal anatomy may be critical to predicting response to therapy. We also observed that bleeding from AU typically first manifested within 1 year of a shift from elemental or hydrolyzed enteral formula to a whole food-based diet (including commercial blenderized feeds), which may indicate that components of the enteral diet play a role in the pathogenesis of AU. Further studies are needed to validate these hypotheses.
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Affiliation(s)
- Wenjing Zong
- From the Division of Gastroenterology, Hepatology, and Nutrition, Children's Hospital of Philadelphia, Philadelphia, PA
| | | | - Arthur Kastl
- From the Division of Gastroenterology, Hepatology, and Nutrition, Children's Hospital of Philadelphia, Philadelphia, PA
| | - Jacqueline Kirsch
- From the Division of Gastroenterology, Hepatology, and Nutrition, Children's Hospital of Philadelphia, Philadelphia, PA
| | - Lindsey Albenberg
- From the Division of Gastroenterology, Hepatology, and Nutrition, Children's Hospital of Philadelphia, Philadelphia, PA
| | - Christina Bales
- From the Division of Gastroenterology, Hepatology, and Nutrition, Children's Hospital of Philadelphia, Philadelphia, PA
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14
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Jørgensen AB, Jonsson I, Friis-Hansen L, Brandstrup B. Collagenase-producing bacteria are common in anastomotic leakage after colorectal surgery: a systematic review. Int J Colorectal Dis 2023; 38:275. [PMID: 38038731 PMCID: PMC10692267 DOI: 10.1007/s00384-023-04562-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 11/08/2023] [Indexed: 12/02/2023]
Abstract
PURPOSE Some gut bacteria can produce enzymes (collagenases) that can break down collagen in the intestinal wall. This could be a part of the pathophysiology of anastomotic leakage (AL). This systematic review aimed to investigate if such bacteria were present more frequently in AL patients versus non-AL patients following colorectal surgery. METHODS This systematic review was reported according to the PRISMA and AMSTAR guidelines. Before the literature search, a study protocol was registered at PROSPERO (CRD42022363454). We searched PubMed, EMBASE, Google Scholar, and Cochrane CENTRAL on April 9th, 2023, for randomized and observational human studies of AL following colorectal surgery with information on gastrointestinal bacteria. The primary outcome was bacteria with the potential to produce collagenase. The risk of bias was assessed with the Newcastle-Ottawa Scale, as all studies were observational. RESULTS We included 15 studies, with a total of 52,945 patients, of which 1,747 had AL, and bacteriological information from feces, mucosa, the resected specimen, or drain fluid was presented. In 10 of the 15 studies, one or more collagenase-producing bacteria were identified in the patients with AL. Neither the bacteria nor the collagenase production were quantified in any of the studies. The studies varied greatly in terms of sample material, analytical method, and time of collection. Studies using DNA sequencing methods did not report findings of collagenase-producing bacteria. CONCLUSION Collagenase-producing bacteria are more common in patients with AL following colorectal surgery than in patients without AL, but the significance is unclear. From the current studies, it is not possible to determine the pathogenicity of the individual gut bacteria.
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Affiliation(s)
- Anders Bech Jørgensen
- Department of Surgery, Holbæk Hospital, Part of Copenhagen University Hospitals, Region Zealand, Denmark.
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
| | - Isabella Jonsson
- Department of Surgery, Holbæk Hospital, Part of Copenhagen University Hospitals, Region Zealand, Denmark
| | - Lennart Friis-Hansen
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
- Department of Clinical Biochemistry, Bispebjerg and Frederiksberg University Hospital, Capital Region, Frederiksberg, Denmark
- Department of Microbiology, Rigshospitalet, Capital Region, Denmark
| | - Birgitte Brandstrup
- Department of Surgery, Holbæk Hospital, Part of Copenhagen University Hospitals, Region Zealand, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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15
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Xuefen Z, Yuanyuan B, Qin L, Xiaoyang W. Nutritional care in patients undergoing laparoscopic/minimally invasive surgeries for gastrointestinal tumours. Wideochir Inne Tech Maloinwazyjne 2023; 18:625-638. [PMID: 38239578 PMCID: PMC10793145 DOI: 10.5114/wiitm.2023.130468] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2023] [Accepted: 07/24/2023] [Indexed: 01/22/2024] Open
Abstract
The introduction of minimally invasive surgeries for gastrointestinal tumours has been associated with many favourable postoperative outcomes and a reduced impact on nutritional status. The literature review begins by discussing the impact of minimally invasive procedures on the nutritional status of patients with gastrointestinal tumours, followed by indications for enteral nutrition (EN) in this population, including preoperative nutritional support and postoperative nutritional support. The review then examines the evidence that favours the use of EN in this population, including studies demonstrating improved outcomes with preoperative EN and reduced postoperative complications with postoperative EN. It also discusses potential strategies for improving outcomes with EN, such as early initiation of feeding and individualized nutrition plans. Overall, current evidence shows that EN improves outcomes, reduces complications, and enhances the quality of life. However, the optimal timing, composition of EN, and long-term outcomes are still unclear, indicating the need for future investigations.
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Affiliation(s)
- Zhou Xuefen
- Department of Gastrointestinal Surgery, Affiliated Kunshan Hospital to Jiangsu University, Suzhou Jiangsu, China
| | - Bian Yuanyuan
- Department of Gastrointestinal Surgery, Affiliated Kunshan Hospital to Jiangsu University, Suzhou Jiangsu, China
| | - Li Qin
- Department of Gastrointestinal Surgery, Affiliated Kunshan Hospital to Jiangsu University, Suzhou Jiangsu, China
| | - Wu Xiaoyang
- Department of Gastrointestinal Surgery, Affiliated Kunshan Hospital to Jiangsu University, Suzhou Jiangsu, China
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16
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Xiao F, Zhu C, Wei X, Chen G, Xu X. Shenhuang plaster enhances intestinal anastomotic healing in rabbits through activation of the TGF-β and Hippo/YAP signaling pathways. J Appl Biomed 2023; 21:208-217. [PMID: 38112460 DOI: 10.32725/jab.2023.018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2023] [Accepted: 10/30/2023] [Indexed: 12/21/2023] Open
Abstract
Although many efforts have been made to improve management strategies and diagnostic methods in the past several decades, the prevention of anastomotic complications, such as anastomotic leaks and strictures, remain a major clinical challenge. Therefore, new molecular pathways need to be identified that regulate anastomotic healing, and to design new treatments for patients after anastomosis to reduce the occurrence of complications. Rabbits were treated with a MST1/2 inhibitor XMU-XP-1, a Chinese medicine formula Shenhuang plaster (SHP) or a control vehicle immediately after surgery. The anastomotic burst pressure, collagen deposition, and hydroxyproline concentration were evaluated at 3 and 7 days after the surgery, and qRT-PCR and western-blot analyses were used to characterize mRNA and protein expression levels. Both XMU-XP-1 and SHP significantly increased anastomotic burst pressure, collagen deposition, and the concentration of hydroxyproline in intestinal anastomotic tissue at postoperative day 7 (POD 7). Importantly, SHP could induce TGF-β1 expression, which activated its downstream target Smad-2 to activate the TGF-β1 signaling pathway. Moreover, SHP reduced the phosphorylation level of YAP and increased its active form, and treatment with verteporfin, a YAP-TEAD complex inhibitor, significantly suppressed the effects induced by SHP during anastomotic tissue healing. This study demonstrated that activation of the Hippo-YAP pathway enhances anastomotic healing, and that SHP enhances both the TGF-β1/Smad and YAP signaling pathways to promote rabbit anastomotic healing after surgery. These results suggest that SHP could be used to treat patients who underwent anastomosis to prevent the occurrence of anastomotic complications.
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Affiliation(s)
| | | | - Xing Wei
- The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou 310006, Zhejiang, China
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17
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Firut A, Margaritescu DN, Turcu-Stiolica A, Bica M, Rotaru I, Patrascu AM, Radu RI, Marinescu D, Patrascu S, Streba CT, Surlin V. Preoperative Immunocyte-Derived Ratios Predict Postoperative Recovery of Gastrointestinal Motility after Colorectal Cancer Surgery. J Clin Med 2023; 12:6338. [PMID: 37834982 PMCID: PMC10573957 DOI: 10.3390/jcm12196338] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2023] [Revised: 08/20/2023] [Accepted: 09/30/2023] [Indexed: 10/15/2023] Open
Abstract
The aim of this study was to assess the role of immunocyte-derived ratios (IDRs), such as the systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR), as markers for the postoperative recovery of gastrointestinal function following colorectal cancer surgery. A retrospective analysis was conducted on a consecutive cohort of 260 patients who underwent radical colorectal cancer surgery within the timeframe spanning from January 2016 to December 2022. Data concerning the postoperative recovery of gastrointestinal function included the I-FEED score, time to pass flatus, toleration for liquids in the first 48 h, and the need for nasogastric tube reinsertion in the immediate postoperative period. A special emphasis was allocated towards the examination of IDRs and their interrelation with the postoperative gastrointestinal functional parameters. The I-FEED score exhibited a positive correlation with the NLR, SII, and PLR. The univariate analysis indicated that all IDRs, multiorgan resection, hemoglobin and protein levels, regional nodal extent of the tumor (N), and obesity significantly affected nasogastric tube reinsertion. The multivariate analysis showed that the SII and N1 stages were risk factors for nasogastric tube reinsertion after colorectal cancer surgery. The SII and multiorgan resection were the only classifiers that remained significant in the multivariable analysis for the toleration for liquids. In summation, certain preoperative IDRs, such as the SII, PLR, and NLR, may hold potential as predictive determinants for postoperative gastrointestinal functional recovery following colorectal cancer surgery.
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Affiliation(s)
- Andreea Firut
- Department of Surgery, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania; (A.F.); (D.N.M.); (M.B.); (V.S.)
| | - Dragos Nicolae Margaritescu
- Department of Surgery, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania; (A.F.); (D.N.M.); (M.B.); (V.S.)
| | - Adina Turcu-Stiolica
- Pharmacoeconomics and Statistical Analysis in Clinical Trials and Pharmaceutical Research, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania;
| | - Marius Bica
- Department of Surgery, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania; (A.F.); (D.N.M.); (M.B.); (V.S.)
| | - Ionela Rotaru
- Department of Hematology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania; (I.R.); (A.-M.P.)
| | - Ana-Maria Patrascu
- Department of Hematology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania; (I.R.); (A.-M.P.)
| | - Razvan Ilie Radu
- Department of Interventional Cardiology, Prof. Dr. C. C. Iliescu Emergency Institute for Cardiovascular Diseases, 022328 Bucharest, Romania;
| | - Daniela Marinescu
- Department of Surgery, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania; (A.F.); (D.N.M.); (M.B.); (V.S.)
| | - Stefan Patrascu
- Department of Surgery, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania; (A.F.); (D.N.M.); (M.B.); (V.S.)
| | - Costin Teodor Streba
- Department of Pulmonology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania;
| | - Valeriu Surlin
- Department of Surgery, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania; (A.F.); (D.N.M.); (M.B.); (V.S.)
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18
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Li X, Ma W, Wang M, Quan Z, Zhang M, Ye J, Li G, Zhou X, Ma T, Wang J, Yang W, Nie Y, Wang J, Kang F. 68Ga-FAPI-04 PET for Surveillance of Anastomotic Recurrence in Postoperative Patients with Gastrointestinal Cancer: a Comparative Study with 18F-FDG PET. Mol Imaging Biol 2023; 25:857-866. [PMID: 37407745 DOI: 10.1007/s11307-023-01835-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2023] [Revised: 05/31/2023] [Accepted: 06/20/2023] [Indexed: 07/07/2023]
Abstract
PURPOSE This study aims to compare the diagnostic efficacy of 68Ga-FAPI-04 PET and 18F-FDG PET for detecting anastomotic recurrence in postoperative patients with gastrointestinal cancer, and to characterize the signal pattern over time at surgical wounds on both PET imaging. METHODS Gastrointestinal cancer patients who planned to 68Ga-FAPI-04 and 18F-FDG PET/CT imaging for postoperative surveillance were involved. The SUVmax at surgical wounds were assessed. Endoscopic pathology confirmed anastomotic recurrence or it was ruled out by imaging and clinical follow-up. The sensitivity, specificity, positive and negative predictive values (PPV and NPV), and accuracy of the two PET imaging in detecting anastomotic recurrence were compared. Relationships between tracer uptake at surgical wounds and postoperative time were also analyzed. RESULTS Compared with non-recurrent patients, the recurrent patients exhibited a significantly higher anastomotic SUVmax on 68Ga-FAPI-04 PET (SUVmax: 9.92 ± 4.36 vs. 2.81 ± 1.86, P = 0.002). Sensitivity, specificity, PPV, NPV, and accuracy of detecting anastomotic recurrence were 100.0%, 87.3%, 41.7%, 100.0%, and 88.3% for 68Ga-FAPI-04 PET, and 60.0%, 81.8%, 23.1%, 95.7%, and 80.0% for 18F-FDG PET, respectively. Although 68Ga-FAPI-04 PET signal at surgical wounds showed a slight trend to decrease with time, no statistical difference was observed over months post-surgery (P > 0.05). CONCLUSIONS Both tracers displayed high NPVs in identifying anastomotic recurrence with a higher sensitivity to 68Ga-FAPI-04. Tracer uptake at anastomotic sites does not decrease significantly over time, which results in low PPVs for both PET. Therefore, it is difficult to differentiate anastomotic recurrence from inflammation on either PET imaging.
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Affiliation(s)
- Xiang Li
- Department of Nuclear Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shaanxi, China
| | - Wenhui Ma
- Department of Nuclear Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shaanxi, China
| | - Min Wang
- Department of Nuclear Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shaanxi, China
| | - Zhiyong Quan
- Department of Nuclear Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shaanxi, China
| | - Mingru Zhang
- Department of Nuclear Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shaanxi, China
| | - Jiajun Ye
- Department of Nuclear Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shaanxi, China
| | - Guiyu Li
- Department of Nuclear Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shaanxi, China
| | - Xiang Zhou
- Department of Nuclear Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shaanxi, China
| | - Taoqi Ma
- Department of Nuclear Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shaanxi, China
| | - Junling Wang
- Department of Nuclear Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shaanxi, China
| | - Weidong Yang
- Department of Nuclear Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shaanxi, China
| | - Yongzhan Nie
- State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, 710032, Shaanxi, China.
| | - Jing Wang
- Department of Nuclear Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shaanxi, China.
| | - Fei Kang
- Department of Nuclear Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shaanxi, China.
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19
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van Helsdingen CPM, Wildeboer ACL, Zafeiropoulou K, Jongen ACHM, Bosmans JWAM, Gallé C, Hakvoort TBM, Gijbels MJJ, de Jonge WJ, Bouvy ND, Li Yim AYF, Derikx JPM. Histology and transcriptome insights into the early processes of intestinal anastomotic healing: a rat model. BJS Open 2023; 7:zrad099. [PMID: 37855751 PMCID: PMC10586197 DOI: 10.1093/bjsopen/zrad099] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2023] [Revised: 07/24/2023] [Accepted: 08/22/2023] [Indexed: 10/20/2023] Open
Abstract
BACKGROUND Understanding the early processes underlying intestinal anastomotic healing is crucial to comprehend the pathophysiology of anastomotic leakage. The aim of this study was to assess normal intestinal anastomotic healing and disturbed healing in rats to investigate morphological, cellular and intrinsic molecular changes in the anastomotic tissue. METHOD Anastomoses were created in two groups of Wistar rats, using four sutures or 12 sutures to mimic anastomotic leakage and anastomotic healing respectively. At 6, 12, 24 hours and 2, 3, 5 and 7 days, anastomotic tissue was assessed macroscopically using the anastomotic complication score and histologically using the modified Ehrlich-Hunt score. Transcriptome analysis was performed to assess differences between anastomotic leakage and anastomotic healing at the first three time points to find affected genes and biological processes. RESULTS Ninety-eight rats were operated on (49 animals in the anastomotic leakage and 49 in the anastomotic healing group) and seven rats analysed at each time point. None of the animals with 12 sutures developed anastomotic leakage macroscopically, whereas 35 of the 49 animals with four sutures developed anastomotic leakage. Histological analysis showed increasing influx of inflammatory cells up to 3 days in anastomotic healing and up to 7 days in anastomotic leakage, and this increase was significantly higher in anastomotic leakage at 5 (P = 0.041) and 7 days (P = 0.003). Transcriptome analyses revealed large differences between anastomotic leakage and anastomotic healing at 6 and 24 hours, mainly driven by an overall downregulation of genes in anastomotic leakage. CONCLUSION Transcriptomic analyses revealed large differences between normal and disturbed healing at 6 hours after surgery, which might eventually serve as early-onset biomarkers for anastomotic leakage.
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Affiliation(s)
- Claire P M van Helsdingen
- Emma Children’s Hospital, Amsterdam UMC, location University of Amsterdam, Paediatric Surgery, Amsterdam, The Netherlands
- Amsterdan UMC, location University of Amsterdam, Tytgat Institute for Liver and Intestinal Research, Amsterdam, The Netherlands
- Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, The Netherlands
- Amsterdam Reproduction and Development, Amsterdam, The Netherlands
| | - Aurelia C L Wildeboer
- Emma Children’s Hospital, Amsterdam UMC, location University of Amsterdam, Paediatric Surgery, Amsterdam, The Netherlands
- GROW, School for Oncology and Developmental Biology, Maastricht University, Maastricht, The Netherlands
| | - Konstantina Zafeiropoulou
- Emma Children’s Hospital, Amsterdam UMC, location University of Amsterdam, Paediatric Surgery, Amsterdam, The Netherlands
- Amsterdan UMC, location University of Amsterdam, Tytgat Institute for Liver and Intestinal Research, Amsterdam, The Netherlands
- Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, The Netherlands
| | - Audrey C H M Jongen
- Department of Surgery, Maastricht University Medical Center, Maastricht, The Netherlands
| | - Joanna W A M Bosmans
- Department of Surgery, Maastricht University Medical Center, Maastricht, The Netherlands
| | - Camille Gallé
- Department of General Surgery, Maastricht University, Maastricht, The Netherlands
| | - Theodorus B M Hakvoort
- Amsterdan UMC, location University of Amsterdam, Tytgat Institute for Liver and Intestinal Research, Amsterdam, The Netherlands
- Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, The Netherlands
| | - Marion J J Gijbels
- Department of Pathology, Maastricht University Medical Center, Maastricht, The Netherlands
- NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, Maastricht, The Netherlands
- Department of Medical Biochemistry, Amsterdam UMC, location University of Amsterdam, Experimental Vascular Biology, Amsterdam, The Netherlands
- Amsterdam Infection and Immunity, Amsterdam, The Netherlands
- Amsterdam Cardiovascular Sciences, Amsterdam, The Netherlands
| | - Wouter J de Jonge
- Amsterdan UMC, location University of Amsterdam, Tytgat Institute for Liver and Intestinal Research, Amsterdam, The Netherlands
- Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, The Netherlands
- Department of Surgery, University of Bonn, Bonn, Germany
| | - Nicole D Bouvy
- Department of Surgery, Maastricht University Medical Center, Maastricht, The Netherlands
- NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, Maastricht, The Netherlands
| | - Andrew Y F Li Yim
- Emma Children’s Hospital, Amsterdam UMC, location University of Amsterdam, Paediatric Surgery, Amsterdam, The Netherlands
- Amsterdan UMC, location University of Amsterdam, Tytgat Institute for Liver and Intestinal Research, Amsterdam, The Netherlands
- Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, The Netherlands
- Amsterdam Reproduction and Development, Amsterdam, The Netherlands
- Department of Human Genetics, Amsterdam UMC, location University of Amsterdam, Genome Diagnostics Laboratory, Amsterdam, The Netherlands
| | - Joep P M Derikx
- Emma Children’s Hospital, Amsterdam UMC, location University of Amsterdam, Paediatric Surgery, Amsterdam, The Netherlands
- Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, The Netherlands
- Amsterdam Reproduction and Development, Amsterdam, The Netherlands
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Golshani P, Park J, Häggström J, Segelman J, Matthiessen P, Lydrup ML, Rutegård M. The modified Glasgow Prognostic Score indicates an increased risk of anastomotic leakage after anterior resection for rectal cancer. Int J Colorectal Dis 2023; 38:200. [PMID: 37470911 PMCID: PMC10359376 DOI: 10.1007/s00384-023-04496-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 07/17/2023] [Indexed: 07/21/2023]
Abstract
BACKGROUND Preoperative inflammation might cause and also be a marker for anastomotic leakage after anterior resection for rectal cancer. Available biomarker indices such as the modified Glasgow Prognostic Score (mGPS) or the C-reactive protein-to-albumin ratio (CAR) may be clinically useful for leakage assessment. METHODS Patients who underwent anterior resection for rectal cancer during 2014-2018 from a multicentre retrospective cohort were included. Data from the Swedish Colorectal Cancer registry and chart review at each hospital were collected. In a subset of patients, preoperative laboratory assessments were available, constituting the exposures mGPS and CAR. Anastomotic leakage within 12 months was the outcome. Causally oriented analyses were conducted with adjustment for confounding, as well as predictive models. RESULTS A total of 418 patients were eligible for analysis. Most patients had mGPS = 0 (84.7%), while mGPS = 1 (10.8%) and mGPS = 2 (4.5%) were less common. mGPS = 2 (OR: 4.11; 95% CI: 1.69-10.03) seemed to confer anastomotic leakage, while this was not seen for mGPS = 1 (OR 1.09; 95% CI: 0.53-2.25). A cut off point of CAR > 0.36 might be indicative of leakage (OR 2.25; 95% CI: 1.21-4.19). Predictive modelling using mGPS rendered an area-under-the-curve of 0.73 (95% CI: 0.67-0.79) at most. DISCUSSION Preoperative inflammation seems to be involved in the development of anastomotic leakage after anterior resection for cancer. Inclusion into prediction models did not result in accurate leakage prediction, but high degrees of systemic inflammation might still be important in clinical decision-making.
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Affiliation(s)
- Parisa Golshani
- Department of Surgery, Regional Council of Gävleborg, Gävle, Sweden
| | - Jennifer Park
- Department of Surgery, SSORG - Scandinavian Surgical Outcomes Research Group, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Jenny Häggström
- Department of Statistics, Umeå School of Business, Economics and Statistics, Umeå University, Umeå, Sweden
| | - Josefin Segelman
- Department of Molecular Medicine and Surgery, Karolinska Institutet, and Ersta Hospital, Stockholm, Sweden
| | - Peter Matthiessen
- Department of Surgery, Faculty of Medicine and Health, Örebro University, Örebro, Sweden
| | - Marie-Louise Lydrup
- Department of Surgery, Skåne University Hospital, Malmö, Lund University, Lund, Sweden
| | - Martin Rutegård
- Department of Surgical and Perioperative Sciences, Surgery, Umeå University, SE-901 85, Umeå, Sweden.
- Wallenberg Centre for Molecular Medicine, Umeå University, Umeå, Sweden.
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Menni A, Moysidis M, Tzikos G, Stavrou G, Tsetis JK, Shrewsbury AD, Filidou E, Kotzampassi K. Looking for the Ideal Probiotic Healing Regime. Nutrients 2023; 15:3055. [PMID: 37447381 DOI: 10.3390/nu15133055] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2023] [Revised: 06/30/2023] [Accepted: 07/05/2023] [Indexed: 07/15/2023] Open
Abstract
Wound healing is a multi-factorial response to tissue injury, aiming to restore tissue continuity. Numerous recent experimental and clinical studies clearly indicate that probiotics are applied topically to promote the wound-healing process. However, the precise mechanism by which they contribute to healing is not yet clear. Each strain appears to exert a distinctive, even multi-factorial action on different phases of the healing process. Given that a multi-probiotic formula exerts better results than a single strain, the pharmaceutical industry has embarked on a race for the production of a formulation containing a combination of probiotics capable of playing a role in all the phases of the healing process. Hence, the object of this review is to describe what is known to date of the distinctive mechanisms of each of the most studied probiotic strains in order to further facilitate research toward the development of combinations of strains and doses, covering the whole spectrum of healing. Eleven probiotic species have been analyzed, the only criterion of inclusion being a minimum of two published research articles.
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Affiliation(s)
- Alexandra Menni
- Department of Surgery, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece
| | - Moysis Moysidis
- Department of Surgery, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece
| | - Georgios Tzikos
- Department of Surgery, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece
| | - George Stavrou
- Department of Colorectal Surgery, Addenbrooke's Hospital, Cambridge CB2 2QQ, UK
| | | | - Anne D Shrewsbury
- Department of Surgery, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece
| | - Eirini Filidou
- Laboratory of Pharmacology, Faculty of Medicine, Democritus University of Thrace, 68100 Alexandroupolis, Greece
| | - Katerina Kotzampassi
- Department of Surgery, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece
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22
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Wildeboer ACL, van Helsdingen CPM, Gallé CG, de Vries RBM, Derikx JPM, Bouvy ND. Enhancing intestinal anastomotic healing using butyrate: Systematic review and meta-analysis of experimental animal studies. PLoS One 2023; 18:e0286716. [PMID: 37310970 DOI: 10.1371/journal.pone.0286716] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2022] [Accepted: 05/22/2023] [Indexed: 06/15/2023] Open
Abstract
BACKGROUND Despite advancements in surgical technique and perioperative care, intestinal anastomoses still have a 10-15 per cent risk of leakage, which results in considerable morbidity and/or mortality. Recent animal studies have suggested that administration of butyrate to the anastomotic site results in enhanced anastomotic strength, which may prevent leakage. This systematic review and meta-analysis summarises current evidence concerning the effect of butyrate administration on anastomotic healing and will form a scientific basis for the development of new research into this subject. METHODS Animal studies on the effect of butyrate-based interventions in models of intestinal anastomotic healing were systematically retrieved from online databases. Bibliographical data, study characteristics and outcome data were extracted, and internal validity of the studies was assessed. Outcomes studied through meta-analysis concerned: anastomotic strength, anastomotic leakage, collagen metabolism and general histologic parameters of wound healing. RESULTS A comprehensive search and selection identified 19 relevant studies containing 41 individual comparisons. Design and conduct of most experiments were poorly reported resulting in an unclear risk of bias. Meta-analyses showed that butyrate administration significantly increases anastomotic strength (SMD 1.24, 0.88 to 1.61), collagen synthesis (SMD 1.44, 0.72 to 2.15) and collagen maturation, making anastomoses less prone to leakage in the early postoperative period (OR 0.37, 0.15 to 0.93). CONCLUSION This systematic review and meta-analysis shows that there is potential ground to investigate the use of butyrate in clinical trials to prevent anastomotic leakage in intestinal surgery. However, more research is necessary to define the best application form, dosage and administration route.
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Affiliation(s)
- Aurelia C L Wildeboer
- Department of Surgery, Maastricht University Medical Centre+ (MUMC+), Maastricht, The Netherlands
- Department of Pediatric Surgery, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam & Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
| | - Claire P M van Helsdingen
- Department of Pediatric Surgery, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam & Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
- Tytgat Institute for Liver and Intestinal Research, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Camille G Gallé
- Department of General Surgery, Maastricht University, Maastricht, The Netherlands
| | - Rob B M de Vries
- Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE), Department for Health Evidence, Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Joep P M Derikx
- Department of Pediatric Surgery, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam & Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
| | - Nicole D Bouvy
- Department of Surgery, Maastricht University Medical Centre+ (MUMC+), Maastricht, The Netherlands
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The Role of Microbiota in Liver Transplantation and Liver Transplantation-Related Biliary Complications. Int J Mol Sci 2023; 24:ijms24054841. [PMID: 36902269 PMCID: PMC10003075 DOI: 10.3390/ijms24054841] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2023] [Revised: 02/22/2023] [Accepted: 02/28/2023] [Indexed: 03/06/2023] Open
Abstract
Liver transplantation as a treatment option for end-stage liver diseases is associated with a relevant risk for complications. On the one hand, immunological factors and associated chronic graft rejection are major causes of morbidity and carry an increased risk of mortality due to liver graft failure. On the other hand, infectious complications have a major impact on patient outcomes. In addition, abdominal or pulmonary infections, and biliary complications, including cholangitis, are common complications in patients after liver transplantation and can also be associated with a risk for mortality. Thereby, these patients already suffer from gut dysbiosis at the time of liver transplantation due to their severe underlying disease, causing end-stage liver failure. Despite an impaired gut-liver axis, repeated antibiotic therapies can cause major changes in the gut microbiome. Due to repeated biliary interventions, the biliary tract is often colonized by several bacteria with a high risk for multi-drug resistant germs causing local and systemic infections before and after liver transplantation. Growing evidence about the role of gut microbiota in the perioperative course and their impact on patient outcomes in liver transplantation is available. However, data about biliary microbiota and their impact on infectious and biliary complications are still sparse. In this comprehensive review, we compile the current evidence for the role of microbiome research in liver transplantation with a focus on biliary complications and infections due to multi-drug resistant germs.
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24
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Boatman S, Kohn J, Jahansouz C. The Influence of the Microbiome on Anastomotic Leak. Clin Colon Rectal Surg 2023; 36:127-132. [PMID: 36844711 PMCID: PMC9946719 DOI: 10.1055/s-0043-1760718] [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: 01/19/2023]
Abstract
Anastomotic leak, defined by the International Study Group of Rectal Cancer as "a communication between the intra- and extraluminal compartments owing to a defect of the integrity of the intestinal wall at the anastomosis," is one of the most devastating complications in colorectal surgery. Much work has been done to identify causes of leak; however, despite advances in surgical technique, the prevalence of anastomotic leak has remained at around 11%. The potential causative role of bacteria in the etiopathology of anastomotic leak was established in the 1950s. More recently, alterations in the colonic microbiome have been shown to affect rates of anastomotic leak. Multiple perioperative factors that alter the homeostasis of the gut microbiota community structure and function have been linked to anastomotic leak after colorectal surgery. Here, we discuss the role of diet, radiation, bowel preparation, medications including nonsteroidal anti-inflammatory drugs, morphine, and antibiotics, and specific microbial pathways that have been implicated in anastomotic leak via their effects on the microbiome.
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Affiliation(s)
- Sonja Boatman
- Department of Colon and Rectal Surgery, University of Minnesota, Minneapolis, Minnesota
| | - Julia Kohn
- Department of Colon and Rectal Surgery, University of Minnesota, Minneapolis, Minnesota
| | - Cyrus Jahansouz
- Department of Colon and Rectal Surgery, University of Minnesota, Minneapolis, Minnesota
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Pinares-Carrillo HD, Ortega-Checa D, Vergel-Ramírez K, Chilca-Alva ML, Núñez-Vergara M. Proteína C reactiva como biomarcador predictivo de fuga anastomótica en cirugía oncológica colorrectal: estudio de cohorte retrospectivo. REVISTA COLOMBIANA DE CIRUGÍA 2023. [DOI: 10.30944/20117582.2269] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/16/2023] Open
Abstract
Introducción. La fuga anastomótica es la complicación más grave del tratamiento quirúrgico del cáncer de colon por su alta morbimortalidad. El diagnóstico evidente, manifestado por la salida de contenido intestinal por drenajes o la herida quirúrgica, ocurre tardíamente (entre el 6º y 8º día). El objetivo de este trabajo fue estudiar la variación de los valores de la proteína C reactiva postoperatoria para hacer un diagnóstico precoz.
Métodos. Estudio observacional, analítico, retrospectivo, de una cohorte de pacientes con neoplasia, en quienes se realizó cirugía oncológica con anastomosis intestinal, entre enero de 2019 y diciembre de 2021. Se midieron los valores en sangre de proteína C reactiva postoperatoria (1°, 3° y 5° días).
Resultados. Se compararon 225 casos operados que no presentaron fuga con 45 casos con fuga. En los casos sin fuga, el valor de proteína C reactiva al 3º día fue de 148 mg/l y al 5º día de 71 mg/l, mientras en los casos con fuga, los valores fueron de 228,24 mg/l y 228,04 mg/l, respectivamente (p<0,05). Para un valor de 197 mg/l al 3º día la sensibilidad fue de 77 % y para un valor de 120 mg/l al 5º día la sensibilidad fue de 84 %.
Conclusión. El mejor resultado de proteína C reactiva postoperatoria para detectar precozmente la fuga anastomótica se observó al 5º día. El valor de 127 mg/l tuvo la mejor sensibilidad, especificidad y valor predictivo negativo, lo cual permitiría el diagnóstico temprano y manejo oportuno de esta complicación.
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Motegi D, Ichikawa H, Bamba T, Muneoka Y, Kano Y, Usui K, Hanyu T, Ishikawa T, Hirose Y, Miura K, Tajima Y, Shimada Y, Sakata J, Nakagawa S, Kosugi SI, Wakai T. Ulcer Scarring in the Gastric Conduit Is a Risk Factor for Anastomotic Leakage After Esophagectomy for Esophageal Cancer. J Gastrointest Surg 2023; 27:250-261. [PMID: 36509899 DOI: 10.1007/s11605-022-05545-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2022] [Accepted: 11/19/2022] [Indexed: 12/15/2022]
Abstract
BACKGROUND Anastomotic leakage (AL) is a serious complication after esophagectomy for esophageal cancer. The objective of this study was to identify the risk factors for AL. METHODS Patients with esophageal cancer who underwent curative esophagectomy and cervical esophagogastric anastomosis between 2009 and 2019 (N = 346) and those between 2020 and 2022 (N = 17) were enrolled in the study to identify the risk factors for AL and the study to assess the association between the risk factors and blood flow in the gastric conduit evaluated by indocyanine green (ICG) fluorescence imaging, respectively. RESULTS AL occurred in 17 out of 346 patients (4.9%). Peptic or endoscopic submucosal dissection (ESD) ulcer scars were independently associated with AL (OR 6.872, 95% CI 2.112-22.365) in addition to diabetes mellitus. The ulcer scars in the anterior/posterior gastric wall were more frequently observed in patients with AL than in those without AL (75.0% vs. 17.4%, P = 0.042). The median flow velocity of ICG fluorescence in the gastric conduits with the scars was significantly lower than in those without the scars (1.17 cm/s vs. 2.23 cm/s, P = 0.004). CONCLUSIONS Peptic or ESD ulcer scarring is a risk factor for AL after esophagectomy in addition to diabetes mellitus. The scars in the anterior/posterior gastric wall are significantly associated with AL, impairing blood flow of the gastric conduit. Preventive interventions and careful postoperative management should be provided to minimize the risk and severity of AL in patients with these risk factors.
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Affiliation(s)
- Daisuke Motegi
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-Dori, Chuo-Ku, Niigata City, Niigata, 951-8510, Japan
| | - Hiroshi Ichikawa
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-Dori, Chuo-Ku, Niigata City, Niigata, 951-8510, Japan.
| | - Takeo Bamba
- Department of Gastroenterological Surgery, Niigata Cancer Center Hospital, 2-15-3 Kawagishi-Cho, Chuo-Ku, Niigata City, Niigata, 951-8566, Japan
| | - Yusuke Muneoka
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-Dori, Chuo-Ku, Niigata City, Niigata, 951-8510, Japan
| | - Yosuke Kano
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-Dori, Chuo-Ku, Niigata City, Niigata, 951-8510, Japan
| | - Kenji Usui
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-Dori, Chuo-Ku, Niigata City, Niigata, 951-8510, Japan
| | - Takaaki Hanyu
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-Dori, Chuo-Ku, Niigata City, Niigata, 951-8510, Japan.,Department of Surgery, Shibata Prefectural Hospital, 1-2-8 Hon-Cho, Shibata City, Niigata, 957-8588, Japan
| | - Takashi Ishikawa
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-Dori, Chuo-Ku, Niigata City, Niigata, 951-8510, Japan
| | - Yuki Hirose
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-Dori, Chuo-Ku, Niigata City, Niigata, 951-8510, Japan
| | - Kohei Miura
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-Dori, Chuo-Ku, Niigata City, Niigata, 951-8510, Japan
| | - Yosuke Tajima
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-Dori, Chuo-Ku, Niigata City, Niigata, 951-8510, Japan
| | - Yoshifumi Shimada
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-Dori, Chuo-Ku, Niigata City, Niigata, 951-8510, Japan
| | - Jun Sakata
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-Dori, Chuo-Ku, Niigata City, Niigata, 951-8510, Japan
| | - Satoru Nakagawa
- Department of Gastroenterological Surgery, Niigata Cancer Center Hospital, 2-15-3 Kawagishi-Cho, Chuo-Ku, Niigata City, Niigata, 951-8566, Japan
| | - Shin-Ichi Kosugi
- Department of Digestive and General Surgery, Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital, 4132 Urasa, Minami-Uonuma City, Niigata, 949-7302, Japan
| | - Toshifumi Wakai
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-Dori, Chuo-Ku, Niigata City, Niigata, 951-8510, Japan
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Liu C, Wang Y, Zhao AR, Hu FA, Fan Q, Han G, Ding G, Fu T, Geng L, Yin H. An alternative asymmetric figure-of-eight single-layer suture technique for bowel anastomosis in an in vitro porcine model. Front Surg 2022; 9:896542. [PMID: 36248362 PMCID: PMC9554239 DOI: 10.3389/fsurg.2022.896542] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2022] [Accepted: 09/05/2022] [Indexed: 11/13/2022] Open
Abstract
Anastomotic techniques are of vital importance in restoring gastrointestinal continuity after resection. An alternative asymmetric figure-of-eight single-layer suture anastomotic technique was introduced and its effects were evaluated in an in vitro porcine model. Twelve 15-cm grossly healthy small intestine segments from a porcine cadaver were harvested and randomly divided into asymmetric figure-of-eight single-layer suture (figure-of-eight suture) and single-layer interrupted suture technique (interrupted suture) groups (n = 6 in each group). The anastomosed bowel was infused with methylene blue solution to test anastomotic leakage. Anastomosis construction time, leakage, and suture material cost were recorded and analyzed statistically using Fisher's exact test and Student's t-test. One anastomotic leakage occurred (16.67%) in the figure-of-eight suture group, and two (33.33%) in the interrupted suture group (p > 0.9999). The anastomosis construction time was relatively short in the figure-of-eight suture group, but the difference did not reach a statistically significant level between the two groups. The mean number of suture knots and the cost of suture material in the figure-of-eight suture group were significantly decreased in comparison to the interrupted suture group (15.67 ± 3.30 vs. 22.17 ± 2.03, 167.11 ± 35.20 vs. 236.45 ± 21.70 CNY, p < 0.01, respectively). Our results suggested that the alternative asymmetric figure-of-eight suture technique was safe and economic for intestinal anastomosis. An in vivo experiment is required to elucidate the effects of this suture technique on the physiological anastomotic healing process.
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Affiliation(s)
- Chen Liu
- The Department of Pediatric Surgery, Binzhou Medical University Hospital, Binzhou, China
- The Department of Surgery, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai, China
| | - Yewen Wang
- The Department of Pediatric Surgery, Binzhou Medical University Hospital, Binzhou, China
| | - Ai-rong Zhao
- The Department of Pharmacy, Binzhou Medical University Hospital, Binzhou, China
| | - Feng-ai Hu
- The Clinical Laboratory, Binzhou Medical University Hospital, Binzhou, China
| | - Qizhong Fan
- The Department of Pharmacy, Binzhou Medical University Hospital, Binzhou, China
| | - Guoxiu Han
- The Department of Pediatric Surgery, Binzhou Medical University Hospital, Binzhou, China
| | - Guojian Ding
- The Department of Pediatric Surgery, Binzhou Medical University Hospital, Binzhou, China
| | - Tingliang Fu
- The Department of Pediatric Surgery, Binzhou Medical University Hospital, Binzhou, China
| | - Lei Geng
- The Department of Pediatric Surgery, Binzhou Medical University Hospital, Binzhou, China
- Correspondence: Lei Geng Hongshan Yin
| | - Hongshan Yin
- The Department of Urology, Binzhou Medical University Hospital, Binzhou, China
- Correspondence: Lei Geng Hongshan Yin
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The Significance of Blood and Peritoneal Fluid Biochemical Markers in Identifying Early Anastomotic Leak following Colorectal Resection-Findings from a Single-Center Study. MEDICINA (KAUNAS, LITHUANIA) 2022; 58:medicina58091253. [PMID: 36143930 PMCID: PMC9502513 DOI: 10.3390/medicina58091253] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/06/2022] [Revised: 09/01/2022] [Accepted: 09/08/2022] [Indexed: 11/18/2022]
Abstract
Background and Objectives: The aim of our study was to evaluate the value of leukocyte, C reactive protein (CRP), procalcitonin, lactate, and carcinoembryonic antigen (CEA) in blood and peritoneal fluid in early recognition of anastomotic leak (AL) after colorectal resections. Materials and Methods: Our pilot prospective cohort study was conducted at the abdominal surgery department at University Medical Center Ljubljana. A total of 43 patients who underwent open or laparoscopic colorectal resection because of benign or malignant etiology were enrolled. All of the patients had primary anastomosis without stoma formation. Results: Three patients in our patient group developed AL (7%). We found a statistically significant elevation of serum lactate levels in patients that developed AL compared to those who did not but noted no statistically relevant difference in the blood or peritoneal fluid levels of other biochemical markers. Conclusions: Elevated lactate levels may be considered a promising biomarker for the early diagnosis of AL, but more research on bigger patient groups is warranted.
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Kuo CY, Wei PL, Chen CC, Lin YK, Kuo LJ. Nomogram to predict permanent stoma in rectal cancer patients after sphincter-saving surgery. World J Gastrointest Surg 2022; 14:765-777. [PMID: 36157368 PMCID: PMC9453330 DOI: 10.4240/wjgs.v14.i8.765] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2022] [Revised: 06/21/2022] [Accepted: 07/22/2022] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Approximately 20 percent of patients with a tumour localized in the low rectum still encounter the possibility of requiring permanent stoma (PS), which can cause drastic changes in lifestyle and physical perceptions.
AIM To determine the risk factors for PS and to develop a prediction model to predict the probability of PS in rectal cancer patients after sphincter-saving surgery.
METHODS A retrospective cohort of 421 rectal cancer patients who underwent radical surgery at Taipei Medical University Hospital between January 2012 and December 2020 was included in this study. Univariate and multivariate analyses were performed to identify the independent risk factors for PS. A nomogram was developed according to the independent risk factors obtained in the multivariate analysis. The performance of the nomogram was assessed using a receiver operating characteristic curve and a calibration curve.
RESULTS The PS rate after sphincter-saving surgery was 15.1% (59/391) in our study after a median follow-up of 47.3 mo (range 7–114 mo). Multivariate logistic regression analysis demonstrated that local recurrence, perirectal abscess, anastomosis site stenosis, perineural invasion, tumor size and operative time were independent risk factors for PS. These identified risk factors were incorporated into the nomogram, and the concordance index of this model was 0.903 (95%CI: 0.851-0.955). According to the calibration curves, the nomogram represents a perfect prediction model.
CONCLUSION Several risk factors for PS after sphincter-saving surgery were identified. Our nomogram exhibited perfect predictive ability and will improve a physician’s ability to communicate the benefits and risks of various treatment options in shared decision making.
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Affiliation(s)
- Chih-Yu Kuo
- Department of Surgery, Taipei Medical University Hospital, Taipei 11031, Taiwan
| | - Po-Li Wei
- Division of Colorectal Surgery, Department of Surgery, Taipei Medical University Hospital, Taipei 11031, Taiwan
- Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan
| | - Chia-Che Chen
- Division of Colorectal Surgery, Department of Surgery, Taipei Medical University Hospital, Taipei 11031, Taiwan
| | - Yen-Kuang Lin
- Graduate Institute of Athletics and Coaching Science, National Taiwan Sport University, Taoyuan 33301, Taiwan
| | - Li-Jen Kuo
- Division of Colorectal Surgery, Department of Surgery, Taipei Medical University Hospital, Taipei 11031, Taiwan
- Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan
- Taipei Cancer Center, Taipei Medical University, Taipei 11031, Taiwan
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Shen J, Dai S, Li Z, Dai W, Hong J, Huang J, Chen J. Effect of Enteral Immunonutrition in Patients Undergoing Surgery for Gastrointestinal Cancer: An Updated Systematic Review and Meta-Analysis. Front Nutr 2022; 9:941975. [PMID: 35845793 PMCID: PMC9277464 DOI: 10.3389/fnut.2022.941975] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2022] [Accepted: 06/09/2022] [Indexed: 11/15/2022] Open
Abstract
Background The efficacy of enteral immunonutrition (EIN) in patients undergoing gastrointestinal cancer surgery remains debatable. This meta-analysis aimed to investigate the effectiveness of EIN administration in patients undergoing surgery for gastrointestinal cancer. Methods From January 2000 to January 2022, PubMed, EMBASE, Cochrane Library, and Web of Science were thoroughly searched for randomized controlled trials (RCTs) with EIN versus standard diet or no supplement in patients undergoing surgery for gastrointestinal cancer. Overall complications and infectious complications were the primary outcomes. The secondary results were non-infectious complications, mortality, length of hospital stay, and enteral nutrition-related complications. Results Thirty-five studies reporting 3,692 patients undergoing surgery for gastrointestinal cancer (including gastric cancer, colorectal cancer, esophageal cancer, periampullary cancer, or pancreatic cancer) were included. Compared with the control group, EIN group had a significantly decreased incidence of overall complications (RR = 0.79, p < 0.001). Infectious complications in patients who received EIN were considerably lower than in the control group (RR = 0.66, p < 0.001). Compared to the control group, the incidence of surgical site infection, abdominal abscess, anastomotic leakage, bacteremia, duration of systemic inflammatory response syndrome (SIRS), and duration of antibiotic therapy was significantly lower in the specific infectious complications treated with EIN. Still, there was no significant difference between the two groups with other infectious complications. Moreover, a substantial shortening in the length of hospital stay was shown in EIN group compared with the control group. Still, no significant effect of EIN was demonstrated in non-infectious complicatios and mortality. The enteral nutrition-related complications had no significant difference between two groups. Conclusions EIN is safe and effective in reducing overall complications, infectious complications, and hospital stay in patients undergoing gastrointestinal cancer surgery (including gastric cancer, colorectal cancer, esophageal cancer, periampullary cancer, or pancreatic cancer).
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Affiliation(s)
- Jingyi Shen
- The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China
| | - Senjie Dai
- The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China
| | - Zongze Li
- The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China
| | - Wei Dai
- The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China
| | - Jiaze Hong
- The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China
| | - Jin Huang
- The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China
| | - Jingjie Chen
- Department of General Surgery, HwaMei Hospital, University of Chinese Academy of Sciences, Ningbo, China
- *Correspondence: Jingjie Chen
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31
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Rosendorf J, Klicova M, Herrmann I, Anthis A, Cervenkova L, Palek R, Treska V, Liska V. Intestinal Anastomotic Healing: What do We Know About Processes Behind Anastomotic Complications. Front Surg 2022; 9:904810. [PMID: 35747439 PMCID: PMC9209641 DOI: 10.3389/fsurg.2022.904810] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2022] [Accepted: 05/11/2022] [Indexed: 11/13/2022] Open
Abstract
Colorectal surgery has developed rapidly in the recent decades. Nevertheless, colorectal anastomotic leakage continues to appear postoperatively in unpleasant rates and leads to life-threatening conditions. The development of valid complication-preventing methods is inefficient in many aspects as we are still lacking knowledge about the basics of the process of anastomotic wound healing in the gastrointestinal tract. Without the proper understanding of the crucial mechanisms, research for prevention of anastomotic leakage is predestined to be unsuccessful. This review article discusses known pathophysiological mechanisms together with the most lately found processes to be further studied. The aim of the article is to facilitate the orientation in the topic, support the better understanding of known mechanisms and suggest promising possibilities and directions for further research.
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Affiliation(s)
- J. Rosendorf
- Department of Surgery, University Hospital in Pilsen, Pilsen, Czech Republic
- Laboratory of Cancer Treatment and Tissue Regeneration, Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic
- Correspondence: Jachym Rosendorf
| | - M. Klicova
- Department of Nonwovens and Nanofibrous Materials, Faculty of Textile Engineering, Technical University of Liberec, Liberec, Czech Republic
| | - I. Herrmann
- Department of Mechanical and Process Engineering, Nanoparticle Systems Engineering Laboratory, ETH Zurich, Switzerland
| | - A. Anthis
- Department of Mechanical and Process Engineering, Nanoparticle Systems Engineering Laboratory, ETH Zurich, Switzerland
| | - L. Cervenkova
- Laboratory of Cancer Treatment and Tissue Regeneration, Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic
| | - R. Palek
- Department of Surgery, University Hospital in Pilsen, Pilsen, Czech Republic
- Laboratory of Cancer Treatment and Tissue Regeneration, Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic
| | - V. Treska
- Laboratory of Cancer Treatment and Tissue Regeneration, Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic
| | - V. Liska
- Department of Surgery, University Hospital in Pilsen, Pilsen, Czech Republic
- Laboratory of Cancer Treatment and Tissue Regeneration, Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic
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Oncel S, Basson MD. Gut homeostasis, injury, and healing: New therapeutic targets. World J Gastroenterol 2022; 28:1725-1750. [PMID: 35633906 PMCID: PMC9099196 DOI: 10.3748/wjg.v28.i17.1725] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/04/2021] [Revised: 12/12/2021] [Accepted: 03/27/2022] [Indexed: 02/06/2023] Open
Abstract
The integrity of the gastrointestinal mucosa plays a crucial role in gut homeostasis, which depends upon the balance between mucosal injury by destructive factors and healing via protective factors. The persistence of noxious agents such as acid, pepsin, nonsteroidal anti-inflammatory drugs, or Helicobacter pylori breaks down the mucosal barrier and injury occurs. Depending upon the size and site of the wound, it is healed by complex and overlapping processes involving membrane resealing, cell spreading, purse-string contraction, restitution, differentiation, angiogenesis, and vasculogenesis, each modulated by extracellular regulators. Unfortunately, the gut does not always heal, leading to such pathology as peptic ulcers or inflammatory bowel disease. Currently available therapeutics such as proton pump inhibitors, histamine-2 receptor antagonists, sucralfate, 5-aminosalicylate, antibiotics, corticosteroids, and immunosuppressants all attempt to minimize or reduce injury to the gastrointestinal tract. More recent studies have focused on improving mucosal defense or directly promoting mucosal repair. Many investigations have sought to enhance mucosal defense by stimulating mucus secretion, mucosal blood flow, or tight junction function. Conversely, new attempts to directly promote mucosal repair target proteins that modulate cytoskeleton dynamics such as tubulin, talin, Ehm2, filamin-a, gelsolin, and flightless I or that proteins regulate focal adhesions dynamics such as focal adhesion kinase. This article summarizes the pathobiology of gastrointestinal mucosal healing and reviews potential new therapeutic targets.
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Affiliation(s)
- Sema Oncel
- Department of Biomedical Sciences, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND 58202, United States
| | - Marc D Basson
- Department of Biomedical Sciences, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND 58202, United States
- Department of Surgery, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND 58202, United States
- Department of Pathology, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND 58202, United States
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The science of anastomotic healing. SEMINARS IN COLON AND RECTAL SURGERY 2022; 33. [DOI: 10.1016/j.scrs.2022.100879] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
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Alverdy JC, Schardey HM. Anastomotic Leak: Toward an Understanding of Its Root Causes. J Gastrointest Surg 2021; 25:2966-2975. [PMID: 34100248 PMCID: PMC8815793 DOI: 10.1007/s11605-021-05048-4] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2021] [Accepted: 05/18/2021] [Indexed: 01/31/2023]
Abstract
BACKGROUND When an anastomotic leak is discussed at a typical surgical morbidity and mortality conference, it is often presented as a due to an error in surgical technique involving ischemia, tension, or device failure. Here we assert that without direct visual analysis of the leak site and its tissue histology, an ex post facto claim that an anastomotic leak is due to an error in surgical technique remains speculative. METHODS The arguments and rationale used to conclude that an anastomotic leak is due to an error in surgical technique are critically reviewed and assessed for their validity. RESULTS No case series or literature exists in which a root cause analysis has been carried out with visual and tissue level evidence to determine the root cause(s) of an anastomotic leak. CONCLUSIONS At the individual case level, declaring that an anastomotic leak is due to an error in surgical technique without clear and compelling evidence either visually and/or at the tissue level to substantiate such a claim remains speculative.
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Affiliation(s)
- John C Alverdy
- Department of Surgery, University of Chicago, Pritzker School of Medicine, 5841 S. Maryland, Chicago, IL, 60637, USA,Corresponding author
| | - Hans Martin Schardey
- Department of General, Visceral, and Transplantation Surgery, Ludwig-Maximilians-University Munich, Marchioninistr. 15, 81377, Munich, Germany and Department of General, Visceral and Vascular Surgery, Agatharied Hospital, Norbert-Kerkel-Platz, 83734, Hausham, Germany
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Trastulli S, Munzi G, Desiderio J, Cirocchi R, Rossi M, Parisi A. Indocyanine green fluorescence angiography versus standard intraoperative methods for prevention of anastomotic leak in colorectal surgery: meta-analysis. Br J Surg 2021; 108:359-372. [PMID: 33778848 DOI: 10.1093/bjs/znaa139] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2020] [Revised: 11/01/2020] [Accepted: 11/22/2020] [Indexed: 12/16/2022]
Abstract
BACKGROUND Assessment of anastomotic blood perfusion with intraoperative indocyanine green fluorescence angiography (ICG-FA) may be effective in preventing anastomotic leak compared with standard intraoperative methods in colorectal surgery. METHODS MEDLINE, PubMed, Cochrane Central Register of Controlled Trials and the Cochrane Library were searched for RCTs and observational studies on intraoperative ICG-FA to May 2020. Odds ratios (ORs), risk differences and mean differences (MDs) were calculated with 95 per cent c.i. based on intention-to-treat analysis. The number needed to treat for an additional beneficial outcome was also estimated. RESULTS Twenty-five comparative studies included a total of 7735 patients. The use of intraoperative ICG fluorescence angiography was linked with a significant reduction in all grades anastomotic leak (OR 0.39 (95 per cent c.i. 0.31 to 0.49), P < 0.001; number needed to treat for an additional beneficial outcome (NNTB) 23) and length of hospital stay (MD -0.72 (95 per cent c.i. -1.22 to -0.21) days, P = 0.006). A significantly lower incidence of grade A (OR 0.33 (0.18 to 0.60), P < 0.001), grade B (OR 0.58 (0.35 to 0.97), P = 0.04) and grade C (OR 0.59 (0.38 to 0.92), P = 0.02) anastomotic leak was demonstrated in favour of ICG-FA. For low or ultra-low rectal resection, the odds of developing anastomotic leakage was 0.32 (0.23 to 0.45) (P < 0.001; NNTB 14). There were no differences in duration of surgery, and no adverse events related to ICG fluorescent injection. CONCLUSION The use of ICG-FA instead of standard intraoperative methods to assess anastomosis blood perfusion in colorectal surgery leads to a significant reduction in anastomotic leakage and in the need for surgical reintervention for anastomotic leak, especially in patients with low or ultra-low rectal resections.
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Affiliation(s)
- S Trastulli
- Department of Emergency and Digestive Surgery, St Mary's Hospital, Terni, Italy
| | - G Munzi
- Department of Surgical and Biomedical Sciences, University of Perugia, St Mary's Hospital, Terni, Italy.,Hepato-Bilio-Pancreatic and Liver Transplant Unit, Department of Surgery, Sapienza University of Rome, Italy
| | - J Desiderio
- Department of Emergency and Digestive Surgery, St Mary's Hospital, Terni, Italy
| | - R Cirocchi
- Department of Surgical and Biomedical Sciences, University of Perugia, St Mary's Hospital, Terni, Italy
| | - M Rossi
- Hepato-Bilio-Pancreatic and Liver Transplant Unit, Department of Surgery, Sapienza University of Rome, Italy
| | - A Parisi
- Department of Emergency and Digestive Surgery, St Mary's Hospital, Terni, Italy
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Mocanu V, Park H, Dang J, Hotte N, Thiesen A, Laffin M, Wang H, Birch D, Madsen K. Timing of Tributyrin Supplementation Differentially Modulates Gastrointestinal Inflammation and Gut Microbial Recolonization Following Murine Ileocecal Resection. Nutrients 2021; 13:nu13062069. [PMID: 34204288 PMCID: PMC8233937 DOI: 10.3390/nu13062069] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2021] [Revised: 06/12/2021] [Accepted: 06/14/2021] [Indexed: 12/31/2022] Open
Abstract
BACKGROUND Gastrointestinal surgery imparts dramatic and lasting imbalances, or dysbiosis, to the composition of finely tuned microbial ecosystems. The aim of the present study was to use a mouse ileocecal resection (ICR) model to determine if tributyrin (TBT) supplementation could prevent the onset of microbial dysbiosis or alternatively enhance the recovery of the gut microbiota and reduce gastrointestinal inflammation. METHODS Male wild-type (129 s1/SvlmJ) mice aged 8-15 weeks were separated into single cages and randomized 1:1:1:1 to each of the four experimental groups: control (CTR), preoperative TBT supplementation (PRE), postoperative TBT supplementation (POS), and combined pre- and postoperative supplementation (TOT). ICR was performed one week from baseline assessment with mice assessed at 1, 2, 3, and 4 weeks postoperatively. Primary outcomes included evaluating changes to gut microbial communities occurring from ICR to 4 weeks. RESULTS A total of 34 mice that underwent ICR (CTR n = 9; PRE n = 10; POS n = 9; TOT n = 6) and reached the primary endpoint were included in the analysis. Postoperative TBT supplementation was associated with an increased recolonization and abundance of anaerobic taxa including Bacteroides thetaiotomicorn, Bacteroides caecimuris, Parabacteroides distasonis, and Clostridia. The microbial recolonization of PRE mice was characterized by a bloom of aerotolerant organisms including Staphylococcus, Lactobacillus, Enteroccaceae, and Peptostreptococcacea. PRE mice had a trend towards decreased ileal inflammation as evidenced by decreased levels of IL-1β (p = 0.09), IL-6 (p = 0.03), and TNF-α (p < 0.05) compared with mice receiving TBT postoperatively. In contrast, POS mice had trends towards reduced colonic inflammation demonstrated by decreased levels of IL-6 (p = 0.07) and TNF-α (p = 0.07). These changes occurred in the absence of changes to fecal short-chain fatty acid concentrations or histologic injury scoring. CONCLUSIONS Taken together, the results of our work demonstrate that the timing of tributyrin supplementation differentially modulates gastrointestinal inflammation and gut microbial recolonization following murine ICR.
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Affiliation(s)
- Valentin Mocanu
- Department of Surgery, University of Alberta, Edmonton, AB T6G 2R3, Canada; (J.D.); (M.L.); (H.W.); (D.B.)
- Correspondence:
| | - Heekuk Park
- Columbia University Medical Center, New York, NY 10032, USA;
| | - Jerry Dang
- Department of Surgery, University of Alberta, Edmonton, AB T6G 2R3, Canada; (J.D.); (M.L.); (H.W.); (D.B.)
| | - Naomi Hotte
- Department of Medicine, University of Alberta, Edmonton, AB T6G 2R3, Canada;
| | - Aducio Thiesen
- Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, AB T6G 2R3, Canada;
| | - Michael Laffin
- Department of Surgery, University of Alberta, Edmonton, AB T6G 2R3, Canada; (J.D.); (M.L.); (H.W.); (D.B.)
| | - Haili Wang
- Department of Surgery, University of Alberta, Edmonton, AB T6G 2R3, Canada; (J.D.); (M.L.); (H.W.); (D.B.)
| | - Daniel Birch
- Department of Surgery, University of Alberta, Edmonton, AB T6G 2R3, Canada; (J.D.); (M.L.); (H.W.); (D.B.)
| | - Karen Madsen
- Division of Gastroenterology, University of Alberta, Edmonton, AB T6G 2R3, Canada;
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Türlü C, Willumsen N, Marando D, Schjerling P, Biskup E, Hannibal J, Jorgensen LN, Ågren MS. A Human Cellular Model for Colorectal Anastomotic Repair: The Effect of Localization and Transforming Growth Factor-β1 Treatment on Collagen Deposition and Biomarkers. Int J Mol Sci 2021; 22:ijms22041616. [PMID: 33562728 PMCID: PMC7914853 DOI: 10.3390/ijms22041616] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2021] [Revised: 02/02/2021] [Accepted: 02/03/2021] [Indexed: 01/01/2023] Open
Abstract
Anastomotic leakage (AL) is a devastating complication after colorectal surgery, possibly due to the loss of stabilizing collagen fibers in the submucosa. Our aim was to assess the formation of collagen in the colon versus the rectum with or without transforming growth factor (TGF)-β1 exposure in a human cellular model of colorectal repair. Primary fibroblasts were isolated by an explant procedure from clinically resected tissue rings during anastomosis construction in 19 consecutive colorectal patients who underwent laparoscopy. The cells, identified as fibroblasts by morphologic characteristics and flow cytometry analysis (CD90+), were cultured for 8 days and in 12 patients in the presence of 1 ng/mL TGF-β1. Total collagen deposition was measured colorimetrically after Sirius red staining of fixed cell layers, and type I, III, and VI collagen biosynthesis and degradation were specifically determined by the biomarkers PINP, PRO-C3, PRO-C6, and C3M in conditioned media by competitive enzyme-linked immunosorbent assays. Total collagen deposition by fibroblasts from the colon and rectum did not significantly differ. TGF-β1 treatment increased PINP, PRO-C6, and total collagen deposition. Mechanistically, TGF-β1 treatment increased COL1A1 and ACTA2 (encoding α-smooth muscle actin), and decreased COL6A1 and MMP2 mRNA levels in colorectal fibroblasts. In conclusion, we found no effect of anatomic localization on collagen production by fibroblasts derived from the large intestine. TGF-β1 represents a potential therapeutic agent for the prevention of AL by increasing type I collagen synthesis and collagen deposition.
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Affiliation(s)
- Ceylan Türlü
- Digestive Disease Center, Bispebjerg Hospital, University of Copenhagen, 2400 Copenhagen, Denmark; (C.T.); (D.M.); (L.N.J.)
| | | | - Debora Marando
- Digestive Disease Center, Bispebjerg Hospital, University of Copenhagen, 2400 Copenhagen, Denmark; (C.T.); (D.M.); (L.N.J.)
| | - Peter Schjerling
- Institute of Sports Medicine Copenhagen, Department of Orthopedic Surgery, Copenhagen University Hospital—Bispebjerg and Frederiksberg, 2400 Copenhagen, Denmark;
- Center for Healthy Aging, Department of Clinical Medicine, University of Copenhagen, 2200 Copenhagen, Denmark
| | - Edyta Biskup
- Department of Dermatology and Copenhagen Wound Healing Center, Bispebjerg Hospital, University of Copenhagen, 2400 Copenhagen, Denmark;
| | - Jens Hannibal
- Department of Clinical Biochemistry, Bispebjerg Hospital, University of Copenhagen, 2400 Copenhagen, Denmark;
| | - Lars N. Jorgensen
- Digestive Disease Center, Bispebjerg Hospital, University of Copenhagen, 2400 Copenhagen, Denmark; (C.T.); (D.M.); (L.N.J.)
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark
| | - Magnus S. Ågren
- Digestive Disease Center, Bispebjerg Hospital, University of Copenhagen, 2400 Copenhagen, Denmark; (C.T.); (D.M.); (L.N.J.)
- Department of Dermatology and Copenhagen Wound Healing Center, Bispebjerg Hospital, University of Copenhagen, 2400 Copenhagen, Denmark;
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark
- Correspondence: ; Tel.: +45-3863-5954
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