|
1
|
Morawski M, Krasnodębski M, Rochoń J, Kubiszewski H, Staszewski M, Kuncewicz M, Krawczyk P, Rykowski P, Bołtuć A, Lewandowski Z, Figiel W, Krawczyk M, Grąt M. Transversalis fascia collagen content and the risk of surgical complications: results of a prospective study. Langenbecks Arch Surg 2025; 410:130. [PMID: 40240627 PMCID: PMC12003564 DOI: 10.1007/s00423-025-03706-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2025] [Accepted: 04/09/2025] [Indexed: 04/18/2025]
Abstract
BACKGROUND Collagen is the major protein of the extracellular matrix that provides mechanical strength to the tissues. The relationship between the development of complications and the quality and quantity of collagen fibres has not been investigated in the literature, yet. METHODS This was a prospective study of 392 patients who underwent subcostal laparotomy for confirmed or suspected gastrointestinal malignancy. Prior to abdominal closure a sample of transversalis fascia was collected. The area covered by collagen (ACC) was measured as the mean area covered by Picosirius stained fibres in three areas of the fascia. The primary endpoint of the study was the occurrence of complications, graded according to the Clavien-Dindo over a 90-day follow-up period. RESULTS 392 patients were included in the study. A transversalis fascia sample was obtained in 354 patients (90.3%) and image assessment yielded a group of 259 specimens that were included in the analysis (66.1%). Predicting the development of complications of at least CD III based on ACC was associated with an AUC of 0.606 (p = 0.027) and an optimal threshold of 0.771. There were significantly fewer complications of at least CD III in the group of patients with ACC ≥ 0.771 (6/125) than in the group below the threshold (25/134) (p < 0.01). CONCLUSIONS Collagen content may serve as an adjunct predictor of surgical risk, although its clinical utility requires further validation. There is a need for further studies on the causal nature of this relationship and modifiable risk factors related to body collagen quality.
Collapse
Affiliation(s)
- Marcin Morawski
- Department of General, Transplant, and Liver Surgery, Medical University of Warsaw, Banacha 1 A, 02 - 097, Warsaw, Poland.
| | - Maciej Krasnodębski
- Department of General, Transplant, and Liver Surgery, Medical University of Warsaw, Banacha 1 A, 02 - 097, Warsaw, Poland
| | - Jakub Rochoń
- Department of General, Transplant, and Liver Surgery, Medical University of Warsaw, Banacha 1 A, 02 - 097, Warsaw, Poland
| | - Hubert Kubiszewski
- Department of General, Transplant, and Liver Surgery, Medical University of Warsaw, Banacha 1 A, 02 - 097, Warsaw, Poland
| | - Mikołaj Staszewski
- Department of General, Transplant, and Liver Surgery, Medical University of Warsaw, Banacha 1 A, 02 - 097, Warsaw, Poland
| | - Mikołaj Kuncewicz
- Department of General, Transplant, and Liver Surgery, Medical University of Warsaw, Banacha 1 A, 02 - 097, Warsaw, Poland
| | - Piotr Krawczyk
- Department of General, Transplant, and Liver Surgery, Medical University of Warsaw, Banacha 1 A, 02 - 097, Warsaw, Poland
| | - Paweł Rykowski
- Department of General, Transplant, and Liver Surgery, Medical University of Warsaw, Banacha 1 A, 02 - 097, Warsaw, Poland
| | - Adam Bołtuć
- Department of General, Transplant, and Liver Surgery, Medical University of Warsaw, Banacha 1 A, 02 - 097, Warsaw, Poland
| | - Zbigniew Lewandowski
- Department of Epidemiology and Biostatistics, Medical University of Warsaw, Warsaw, Poland
| | - Wojciech Figiel
- Department of General, Transplant, and Liver Surgery, Medical University of Warsaw, Banacha 1 A, 02 - 097, Warsaw, Poland
| | - Marek Krawczyk
- Department of General, Transplant, and Liver Surgery, Medical University of Warsaw, Banacha 1 A, 02 - 097, Warsaw, Poland
| | - Michał Grąt
- Department of General, Transplant, and Liver Surgery, Medical University of Warsaw, Banacha 1 A, 02 - 097, Warsaw, Poland
| |
Collapse
|
|
2
|
Ntampakis G, Pramateftakis MG, Anestiadou E, Bitsianis S, Ioannidis O, Bekiari C, Koliakos G, Karakota M, Tsakona A, Cheva A, Angelopoulos S. Experimental models of high-risk bowel anastomosis in rats: A systematic review. World J Exp Med 2024; 14:94135. [PMID: 38948424 PMCID: PMC11212746 DOI: 10.5493/wjem.v14.i2.94135] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2024] [Revised: 04/23/2024] [Accepted: 05/10/2024] [Indexed: 06/19/2024] Open
Abstract
BACKGROUND Anastomotic leaks remain one of the most dreaded complications in gastrointestinal surgery causing significant morbidity, that negatively affect the patients' quality of life. Experimental studies play an important role in understanding the pathophysiological background of anastomotic healing and there are still many fields that require further investigation. Knowledge drawn from these studies can lead to interventions or techniques that can reduce the risk of anastomotic leak in patients with high-risk features. Despite the advances in experimental protocols and techniques, designing a high-quality study is still challenging for the investigators as there is a plethora of different models used. AIM To review current state of the art for experimental protocols in high-risk anastomosis in rats. METHODS This systematic review was performed according to The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. To identify eligible studies, a comprehensive literature search was performed in the electronic databases PubMed (MEDLINE) and Scopus, covering the period from conception until 18 October 2023. RESULTS From our search strategy 102 studies were included and were categorized based on the mechanism used to create a high-risk anastomosis. Methods of assessing anastomotic healing were extracted and were individually appraised. CONCLUSION Anastomotic healing studies have evolved over the last decades, but the findings are yet to be translated into human studies. There is a need for high-quality, well-designed studies that will help to the better understanding of the pathophysiology of anastomotic healing and the effects of various interventions.
Collapse
Affiliation(s)
- Georgios Ntampakis
- Fourth Department of Surgery, Medical School, Aristotle University of Thessaloniki, Thessaloniki 57010, Greece
| | | | - Elissavet Anestiadou
- Fourth Department of Surgery, Medical School, Aristotle University of Thessaloniki, Thessaloniki 57010, Greece
| | - Stefanos Bitsianis
- Fourth Department of Surgery, Medical School, Aristotle University of Thessaloniki, Thessaloniki 57010, Greece
| | - Orestis Ioannidis
- Fourth Department of Surgery, Medical School, Aristotle University of Thessaloniki, Thessaloniki 57010, Greece
| | - Chryssa Bekiari
- Laboratory of Anatomy and Histology, School of Veterinary Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece
- Experimental and Research Center, Papageorgiou General Hospital of Thessaloniki, Thessaloniki 56403, Greece
| | - George Koliakos
- Laboratory of Biochemistry, Faculty of Medicine, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece
| | - Maria Karakota
- Laboratory of Biochemistry, Faculty of Medicine, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece
| | - Anastasia Tsakona
- Department of Pathology, Faculty of Medicine, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece
| | - Angeliki Cheva
- Department of Pathology, Faculty of Medicine, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece
| | - Stamatios Angelopoulos
- Fourth Department of Surgery, Medical School, Aristotle University of Thessaloniki, Thessaloniki 57010, Greece
| |
Collapse
|
|
3
|
Zhuang ZM, Wang Y, Feng ZX, Lin XY, Wang ZC, Zhong XC, Guo K, Zhong YF, Fang QQ, Wu XJ, Chen J, Tan WQ. Targeting Diverse Wounds and Scars: Recent Innovative Bio-design of Microneedle Patch for Comprehensive Management. SMALL (WEINHEIM AN DER BERGSTRASSE, GERMANY) 2024; 20:e2306565. [PMID: 38037685 DOI: 10.1002/smll.202306565] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/01/2023] [Revised: 09/16/2023] [Indexed: 12/02/2023]
Abstract
Wounds and the subsequent formation of scars constitute a unified and complex phased process. Effective treatment is crucial; however, the diverse therapeutic approaches for different wounds and scars, as well as varying treatment needs at different stages, present significant challenges in selecting appropriate interventions. Microneedle patch (MNP), as a novel minimally invasive transdermal drug delivery system, has the potential for integrated and programmed treatment of various diseases and has shown promising applications in different types of wounds and scars. In this comprehensive review, the latest applications and biotechnological innovations of MNPs in these fields are thoroughly explored, summarizing their powerful abilities to accelerate healing, inhibit scar formation, and manage related symptoms. Moreover, potential applications in various scenarios are discussed. Additionally, the side effects, manufacturing processes, and material selection to explore the clinical translational potential are investigated. This groundwork can provide a theoretical basis and serve as a catalyst for future innovations in the pursuit of favorable therapeutic options for skin tissue regeneration.
Collapse
Affiliation(s)
- Ze-Ming Zhuang
- Department of Plastic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 3 East Qingchun Road, Hangzhou, 310016, P. R. China
| | - Yong Wang
- Department of Plastic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 3 East Qingchun Road, Hangzhou, 310016, P. R. China
| | - Zi-Xuan Feng
- Department of Plastic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 3 East Qingchun Road, Hangzhou, 310016, P. R. China
| | - Xiao-Ying Lin
- Department of Plastic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 3 East Qingchun Road, Hangzhou, 310016, P. R. China
| | - Zheng-Cai Wang
- Department of Plastic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 3 East Qingchun Road, Hangzhou, 310016, P. R. China
| | - Xin-Cao Zhong
- Department of Plastic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 3 East Qingchun Road, Hangzhou, 310016, P. R. China
| | - Kai Guo
- Department of Plastic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 3 East Qingchun Road, Hangzhou, 310016, P. R. China
| | - Yu-Fan Zhong
- Department of Plastic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 3 East Qingchun Road, Hangzhou, 310016, P. R. China
| | - Qing-Qing Fang
- Department of Plastic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 3 East Qingchun Road, Hangzhou, 310016, P. R. China
| | - Xiao-Jin Wu
- Department of Ultrasound in Medicine, The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, 322000, P. R. China
| | - Jian Chen
- Department of Ultrasound in Medicine, The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, 322000, P. R. China
| | - Wei-Qiang Tan
- Department of Plastic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 3 East Qingchun Road, Hangzhou, 310016, P. R. China
| |
Collapse
|
|
4
|
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).
Collapse
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.
| |
Collapse
|
|
5
|
Wang L, Qu Y, Li W, Wang K, Qin S. Effects and metabolism of fish collagen sponge in repairing acute wounds of rat skin. Front Bioeng Biotechnol 2023; 11:1087139. [PMID: 36911203 PMCID: PMC9992718 DOI: 10.3389/fbioe.2023.1087139] [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: 11/02/2022] [Accepted: 02/14/2023] [Indexed: 02/24/2023] Open
Abstract
Objective: Study the repair effect of tilapia collagen on acute wounds, and the effect on the expression level of related genes and its metabolic direction in the repair process. Materials and methods: After the full-thickness skin defect model was constructed in standard deviation rats, the wound healing effect was observed and evaluated by means of characterization, histology, and immunohistochemistry. RT-PCR, fluorescence tracer, frozen section and other techniques were used to observe the effect of fish collagen on the expression of related genes and its metabolic direction in the process of wound repair. Results: After implantation, there was no immune rejection reaction, fish collagen fused with new collagen fibers in the early stage of wound repair, and was gradually degraded and replaced by new collagen in the later stage. It has excellent performance in inducing vascular growth, promoting collagen deposition and maturation, and re-epithelialization. The results of fluorescent tracer showed that fish collagen was decomposed, and the decomposition products were involved in the wound repair process and remained at the wound site as a part of the new tissue. RT-PCR results showed that, without affecting collagen deposition, the expression level of collagen-related genes was down-regulated due to the implantation of fish collagen. Conclusion: Fish collagen has good biocompatibility and wound repair ability. It is decomposed and utilized in the process of wound repair to form new tissues.
Collapse
Affiliation(s)
- Lei Wang
- The Affiliated Hospital of Weifang Medical University, Weifang, China.,Key Laboratory of Biology and Bioresource Utilization, Yantai Institute of Coastal Zone Research, Chinese Academy of Sciences, Yantai, China.,University of Chinese Academy of Sciences, Yantai, China
| | - Yan Qu
- The Affiliated Hospital of Weifang Medical University, Weifang, China
| | - Wenjun Li
- Key Laboratory of Biology and Bioresource Utilization, Yantai Institute of Coastal Zone Research, Chinese Academy of Sciences, Yantai, China
| | - Kai Wang
- Department of Orthopedics, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, China
| | - Song Qin
- Key Laboratory of Biology and Bioresource Utilization, Yantai Institute of Coastal Zone Research, Chinese Academy of Sciences, Yantai, China
| |
Collapse
|
|
6
|
van der Does de Willebois EML, Duijvestein M, Wasmann KA, D'Haens GRAM, van der Bilt JDW, Mundt MW, Hompes R, van der Vlugt M, Buskens CJ, Bemelman WA. Endoscopic Recurrence or Anastomotic Wound Healing Phenomenon after Ileocolic Resection for Crohn's Disease: The Challenges of Accurate Endoscopic Scoring. J Crohns Colitis 2022; 17:693-699. [PMID: 36382539 PMCID: PMC10155740 DOI: 10.1093/ecco-jcc/jjac175] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2022] [Indexed: 11/17/2022]
Abstract
BACKGROUND AND AIMS Adequate endoscopic scoring in Crohn's disease (CD) is crucial, as dictates the need for initiating postoperative medical therapy and is utilized as outcome parameter in clinical trials. We aimed to observe anastomotic wound healing in relation to endoscopic scoring of both inverted and everted stapled lines in side-to-side anastomoses. METHODS Two prospective patient cohorts were included: ileocolic resection (ICR) for CD, and right-sided colon resection for colorectal cancer (CRC). Videos taken during colonoscopy six months postoperatively were evaluated. The SES-CD and modified Rutgeerts score were determined. Primary outcome was the presence of ulcerations in CD patients on both the inverted and everted stapled lines. Secondary outcomes were the presence of anastomotic ulcerations in CRC patients and the number of cases having ulcerations exclusively at the inverted stapled line. RESULTS Of the 82 patients included in the CD cohort, ulcerations were present in 63/82 (76·8%) at the inverted- versus 1/71 (1·4%) at the everted stapled line. Likewise in the CRC cohort, ulcerations were present in 4/6 (67·7%) at the inverted versus 0/6 (0%) at the everted stapled line. 27% of the 63 patients in the CD cohort had ulcerations exclusively on the inverted stapled line. CONCLUSION Inverted stapled lines heal with ulcerations, whereas the everted stapled line heal without any ulcerations, both in CD and non-CD patients. The abnormalities at the inverted stapled line might interfere with endoscopic scoring of recurrence, with potentially an impact on patients' quality of life and on health-care costs if postoperative treatment is initiated incorrectly.
Collapse
Affiliation(s)
- Eline M L van der Does de Willebois
- Department of Surgery, Amsterdam UMC, Location University of Amsterdam, Amsterdam, the Netherlands.,Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, the Netherlands
| | - Marjolijn Duijvestein
- Department of Gastroenterology and Hepatology, Amsterdam UMC, location University of Amsterdam, Amsterdam, the Netherlands.,Department of Gastroenterology, Radboudumc, Nijmegen, the Netherlands
| | - Karin A Wasmann
- Department of Surgery, UMC Utrecht, Utrecht, the Netherlands
| | - Geert R A M D'Haens
- Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, the Netherlands.,Department of Gastroenterology and Hepatology, Amsterdam UMC, location University of Amsterdam, Amsterdam, the Netherlands
| | | | - Marco W Mundt
- Department of Gastroenterology, Flevoziekenhuis, Almere, the Netherlands
| | - Roel Hompes
- Department of Surgery, Amsterdam UMC, Location University of Amsterdam, Amsterdam, the Netherlands.,Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, the Netherlands
| | - Manon van der Vlugt
- Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, the Netherlands.,Department of Gastroenterology and Hepatology, Amsterdam UMC, location University of Amsterdam, Amsterdam, the Netherlands
| | - Christianne J Buskens
- Department of Surgery, Amsterdam UMC, Location University of Amsterdam, Amsterdam, the Netherlands.,Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, the Netherlands
| | - Willem A Bemelman
- Department of Surgery, Amsterdam UMC, Location University of Amsterdam, Amsterdam, the Netherlands.,Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, the Netherlands.,IBD unit, IRCCS Ospedale San Raffaele, Milan, Italy
| | | |
Collapse
|
|
7
|
Cira K, Stocker F, Reischl S, Obermeier A, Friess H, Burgkart R, Neumann PA. Coating of Intestinal Anastomoses for Prevention of Postoperative Leakage: A Systematic Review and Meta-Analysis. Front Surg 2022; 9:882173. [PMID: 35769150 PMCID: PMC9235828 DOI: 10.3389/fsurg.2022.882173] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2022] [Accepted: 04/05/2022] [Indexed: 11/13/2022] Open
Abstract
Background For several decades, scientific efforts have been taken to develop strategies and medical aids for the reduction of anastomotic complications after intestinal surgery. Still, anastomotic leakage (AL) represents a frequently occurring postoperative complication with serious consequences on health, quality of life, and economic aspects. Approaches using collagen and/or fibrin-based sealants to cover intestinal anastomoses have shown promising effects toward leak reduction; however, they have not reached routine use yet. To assess the effects of covering intestinal anastomoses with collagen and/or fibrin-based sealants on postoperative leakage, a systematic review and meta-analysis were conducted. Method PubMed, Web of Science, Cochrane Library, and Scopus (01/01/1964 to 17/01/2022) were searched to identify studies investigating the effects of coating any intestinal anastomoses with collagen and/or fibrin-based sealants on postoperative AL, reoperation rates, Clavien-Dindo major complication, mortality, and hospitalization length. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Results Overall, 15 studies (five randomized controlled trials, three nonrandomized intervention studies, six observational cohort studies) examining 1,387 patients in the intervention group and 2,243 in the control group were included. Using fixed-effects meta-analysis (I 2 < 50%), patients with coated intestinal anastomoses presented significantly lower AL rates (OR = 0.37; 95% CI 0.27-0.52; p < 0.00001), reoperation rates (OR, 0.21; 95% CI, 0.10-0.47; p = 0.0001), and Clavien-Dindo major complication rates (OR, 0.54; 95% CI, 0.35-0.84; p = 0.006) in comparison to controls, with results remaining stable in sensitivity and subgroup analyses (stratified by study design, age group, intervention used, location of anastomoses, and indication for surgery). The length of hospitalization was significantly shorter in the intervention group (weighted mean difference (WMD), -1.96; 95% CI, -3.21, -0.71; p = 0.002) using random-effects meta-analysis (I 2 ≥ 50%), especially for patients with surgery of upper gastrointestinal malignancy (WMD, -4.94; 95% CI, -7.98, -1.90; p = 0.001). Conclusion The application of collagen-based laminar biomaterials or fibrin sealants on intestinal anastomoses can significantly reduce postoperative rates of AL and its sequelae. Coating of intestinal anastomoses could be a step toward effective and sustainable leak prevention. To assess the validity and robustness of these findings, further clinical studies need to be conducted.
Collapse
Affiliation(s)
- Kamacay Cira
- Department of Surgery, School of Medicine, Klinikum rechts der Isar, Technical University of Munich, Munich, Bavaria, Germany
| | - Felix Stocker
- Department of Surgery, School of Medicine, Klinikum rechts der Isar, Technical University of Munich, Munich, Bavaria, Germany
| | - Stefan Reischl
- Institute of Diagnostic and Interventional Radiology, School of Medicine, Klinikum rechts der Isar, Technical University of Munich, Munich, Bavaria, Germany
| | - Andreas Obermeier
- Department of Orthopaedics and Sports Orthopaedics, School of Medicine, Klinikum rechts der Isar, Technical University of Munich, Munich, Bavaria, Germany
| | - Helmut Friess
- Department of Surgery, School of Medicine, Klinikum rechts der Isar, Technical University of Munich, Munich, Bavaria, Germany
| | - Rainer Burgkart
- Department of Orthopaedics and Sports Orthopaedics, School of Medicine, Klinikum rechts der Isar, Technical University of Munich, Munich, Bavaria, Germany
| | - Philipp-Alexander Neumann
- Department of Surgery, School of Medicine, Klinikum rechts der Isar, Technical University of Munich, Munich, Bavaria, Germany
| |
Collapse
|
|
8
|
Tan Y, Rajoka MSR, Ke Z, Mehwish HM, Deng W, Li J, Qin W, Zhao L, Wu Y. Effect of Squid Cartilage Chitosan Molecular Structure on the Properties of Its Monofilament as an Absorbable Surgical Suture. Polymers (Basel) 2022; 14:polym14071306. [PMID: 35406180 PMCID: PMC9003387 DOI: 10.3390/polym14071306] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2021] [Revised: 03/07/2022] [Accepted: 03/11/2022] [Indexed: 02/05/2023] Open
Abstract
Suture is an important part of surgery, and wounds closing after surgery remains a challenge for postoperative care. Currently, silk, linen fiber, and cotton are available in the market as non-absorbable suture biomaterials. So, there is an urgent need to develop a novel suture with advantageous characteristics compared to the ones available on the market. In present study, a series of ultra-high molecular weight chitosan with different DD and MV were prepared from squid cartilage by alkaline treatment and ultrasonic degradation. The corresponding chitosan monofilaments were prepared by a wet spinning process and were characterized as sutures. The effects of the DD and MV of chitosan on the properties of its monofilament were studied, including surface morphology, mechanical property, swelling ratio, ash content, in vitro enzymatic degradation, and in vitro cytotoxicity. According to the results, AS-85 was chosen to be the best suitable as an absorbable surgical suture, which was spun from squid cartilage chitosan with DD~85% and MV~1.2 × 106. The outcome of the present study might derive tremendous possibilities for the utilization of squid cartilage β-chitin for biomedical applications.
Collapse
Affiliation(s)
- Yongxin Tan
- Department of Food Science and Engineering, College of Chemistry and Chemical Engineering, Shenzhen University, Shenzhen 518060, China; (Y.T.); (M.S.R.R.); (W.D.); (J.L.); (W.Q.)
| | - Muhammad Shahid Riaz Rajoka
- Department of Food Science and Engineering, College of Chemistry and Chemical Engineering, Shenzhen University, Shenzhen 518060, China; (Y.T.); (M.S.R.R.); (W.D.); (J.L.); (W.Q.)
- Department of Pharmacy, Health Science Center, Shenzhen University, Shenzhen 518060, China;
- Food and Feed Immunology Group, Graduate School of Agricultural Science, Tohoku University, Sendai 980-8572, Japan
| | - Zekai Ke
- Department of Orthopaedics, Shenzhen University General Hospital, Shenzhen University Clinical Medical Academy, Shenzhen 518060, China;
| | - Hafiza Mahreen Mehwish
- Department of Pharmacy, Health Science Center, Shenzhen University, Shenzhen 518060, China;
- Food and Feed Immunology Group, Graduate School of Agricultural Science, Tohoku University, Sendai 980-8572, Japan
| | - Wenjing Deng
- Department of Food Science and Engineering, College of Chemistry and Chemical Engineering, Shenzhen University, Shenzhen 518060, China; (Y.T.); (M.S.R.R.); (W.D.); (J.L.); (W.Q.)
| | - Jiaying Li
- Department of Food Science and Engineering, College of Chemistry and Chemical Engineering, Shenzhen University, Shenzhen 518060, China; (Y.T.); (M.S.R.R.); (W.D.); (J.L.); (W.Q.)
| | - Wenqian Qin
- Department of Food Science and Engineering, College of Chemistry and Chemical Engineering, Shenzhen University, Shenzhen 518060, China; (Y.T.); (M.S.R.R.); (W.D.); (J.L.); (W.Q.)
| | - Liqing Zhao
- Department of Food Science and Engineering, College of Chemistry and Chemical Engineering, Shenzhen University, Shenzhen 518060, China; (Y.T.); (M.S.R.R.); (W.D.); (J.L.); (W.Q.)
- Correspondence: (L.Z.); (Y.W.)
| | - Yiguang Wu
- Department of Food Science and Engineering, College of Chemistry and Chemical Engineering, Shenzhen University, Shenzhen 518060, China; (Y.T.); (M.S.R.R.); (W.D.); (J.L.); (W.Q.)
- Correspondence: (L.Z.); (Y.W.)
| |
Collapse
|
|
9
|
Huang Y, Hu Y, Lin Y, Fu J, Wu J, Fang C, Liu M, Hong Y. Evaluation of Fibrin Sealant in Prevention of Cervical Anastomotic Leakage After McKeown Esophagectomy: A Single-Center, Retrospective Study. Ann Surg Oncol 2021; 28:6390-6397. [PMID: 33786677 DOI: 10.1245/s10434-021-09877-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2020] [Accepted: 03/05/2021] [Indexed: 12/13/2022]
Abstract
BACKGROUND Anastomotic leakage remains an issue after esophagectomy for patients with esophageal or esophagogastric junction cancer. Previous studies have indicated that the intraoperative application of fibrin sealant may reduce the incidence of postoperative anastomotic leakage. This retrospective study was aimed to evaluate the efficacy and safety of fibrin sealant in the prevention of anastomotic leakage in patients undergoing McKeown esophagectomy. METHODS We designed a single-center, retrospective study. Between January 2018 and December 2019, 227 patients with esophageal or esophagogastric junction cancer undergoing McKeown esophagectomy performed by our team were retrospectively identified, of whom 86 patients were included in the FS group and 141 patients were included in the control group. Intraoperatively, 2.5 ml of porcine fibrin sealant was applied circumferentially to the cervical anastomosis after the anastomosis was created in the FS group. The primary outcome was the incidence of cervical anastomotic leakage within the first three months after surgery. RESULTS The differences in baseline clinical characteristics between the two groups were not significant except for a history of drinking. In the FS group, the postoperative cervical anastomotic leakage rate was lower (FS group: 4.7% [4 of 82] vs. control group: 19.9% [28 of 141], p < 0.01). Multivariate logistic regression showed that the intraoperative application of fibrin sealant was an independent protective factor for anastomotic leakage (OR 0.169, 95% CI 0.055-0.515, p = 0.002). CONCLUSIONS The intraoperative application of fibrin sealant could possibly prevent cervical anastomotic leakage after McKeown esophagectomy with satisfactory safety. Further prospective clinical trials are warranted.
Collapse
Affiliation(s)
- Yan Huang
- Department of Thoracic Surgery, State Key Laboratory of Oncology in South China, Guangdong Esophageal Cancer Institute, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou City, Guangdong Province, China
| | - Yihuai Hu
- Department of Thoracic Surgery, State Key Laboratory of Oncology in South China, Guangdong Esophageal Cancer Institute, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou City, Guangdong Province, China
| | - Yaobin Lin
- Department of Thoracic Surgery, State Key Laboratory of Oncology in South China, Guangdong Esophageal Cancer Institute, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou City, Guangdong Province, China
| | - Jianhua Fu
- Department of Thoracic Surgery, State Key Laboratory of Oncology in South China, Guangdong Esophageal Cancer Institute, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou City, Guangdong Province, China
| | - Jiadi Wu
- Department of Thoracic Surgery, State Key Laboratory of Oncology in South China, Guangdong Esophageal Cancer Institute, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou City, Guangdong Province, China
| | - Caiyan Fang
- Department of Thoracic Surgery, State Key Laboratory of Oncology in South China, Guangdong Esophageal Cancer Institute, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou City, Guangdong Province, China
| | - Min Liu
- Department of Ultrasound and Electrocardiogram, State Key Laboratory of Oncology in South China, Guangdong Esophageal Cancer Institute, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou City, Guangdong Province, China
| | - Yang Hong
- Department of Thoracic Surgery, State Key Laboratory of Oncology in South China, Guangdong Esophageal Cancer Institute, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou City, Guangdong Province, China.
| |
Collapse
|
|
10
|
Lin YB, Fu JH, Huang Y, Hu YH, Luo KJ, Wang KX, Bella AÉ, Situ DR, Chen JY, Lin T, D’Journo XB, Novoa NM, Brunelli A, Fernando HC, Cerfolio RJ, Ismail M, Yang H, the AME Thoracic Surgery Collaborative Group. Fibrin sealant for esophageal anastomosis: A phase II study. World J Gastrointest Oncol 2020; 12:651-662. [PMID: 32699580 PMCID: PMC7340992 DOI: 10.4251/wjgo.v12.i6.651] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2020] [Revised: 03/28/2020] [Accepted: 05/05/2020] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Esophagectomy is a pivotal curative modality for localized esophageal or esophagogastric junction cancer (EC or EJC). Postoperative anastomotic leakage (AL) remains problematic. The use of fibrin sealant (FS) may improve the strength of esophageal anastomosis and reduce the incidence of AL.
AIM To assess the efficacy and safety of applying FS to prevent AL in patients with EC or EJC.
METHODS In this single-arm, phase II trial (Clinicaltrial.gov identifier: NCT03529266), we recruited patients aged 18-80 years with resectable EC or EJC clinically staged as T1-4aN0-3M0. An open or minimally invasive McKeown esophagectomy was performed with a circular stapled anastomosis. After performing the anastomosis, 2.5 mL of porcine FS was applied circumferentially. The primary endpoint was the proportion of patients with AL within 3 mo.
RESULTS From June 4, 2018, to December 29, 2018, 57 patients were enrolled. At the data cutoff date (June 30, 2019), three (5.3%) of the 57 patients had developed AL, including two (3.5%) with esophagogastric AL and one (1.8%) with gastric fistula. The incidence of anastomotic stricture and other major postoperative complications was 1.8% and 17.5%, respectively. The median time needed to resume oral feeding after operation was 8 d (Interquartile range: 7.0-9.0 d). No adverse events related to FS were recorded. No deaths occurred within 90 d after surgery.
CONCLUSION Perioperative sealing with porcine FS appears safe and may prevent AL after esophagectomy in patients with resectable EC or EJC. Further phase III studies are warranted.
Collapse
Affiliation(s)
- Yao-Bin Lin
- Department of Thoracic Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Esophageal Cancer Institute, Sun Yat-sen University Cancer Center, Guangzhou 510060, Guangdong Province, China
| | - Jian-Hua Fu
- Department of Thoracic Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Esophageal Cancer Institute, Sun Yat-sen University Cancer Center, Guangzhou 510060, Guangdong Province, China
| | - Yan Huang
- Department of Thoracic Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Esophageal Cancer Institute, Sun Yat-sen University Cancer Center, Guangzhou 510060, Guangdong Province, China
| | - Yi-Huai Hu
- Department of Thoracic Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Esophageal Cancer Institute, Sun Yat-sen University Cancer Center, Guangzhou 510060, Guangdong Province, China
| | - Kong-Jia Luo
- Department of Thoracic Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Esophageal Cancer Institute, Sun Yat-sen University Cancer Center, Guangzhou 510060, Guangdong Province, China
| | - Ke-Xi Wang
- Department of Thoracic Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Esophageal Cancer Institute, Sun Yat-sen University Cancer Center, Guangzhou 510060, Guangdong Province, China
| | - Amos Éla Bella
- Department of Thoracic Surgery, Avicenne Hospital, Bobigny 93000, France
- Department of Surgery and Specialties, Faculty of Medicine and Biomedical Sciences, University of Yaoundé I, Yaoundé, Cameroon
| | - Dong-Rong Situ
- Department of Surgery, Royal Darwin Hospital, Northern Territory 0811, Australia
| | - Ji-Yang Chen
- Department of Thoracic Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Esophageal Cancer Institute, Sun Yat-sen University Cancer Center, Guangzhou 510060, Guangdong Province, China
| | - Ting Lin
- Department of Thoracic Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Esophageal Cancer Institute, Sun Yat-sen University Cancer Center, Guangzhou 510060, Guangdong Province, China
| | - Xavier B D’Journo
- Department of Thoracic Surgery and Diseases of Esophagus, Aix-Marseille University, Hôpital Nord, Marseille 13915, France
| | - Nuria M Novoa
- Thoracic Surgery Service, University Hospital of Salamanca, Salamanca 37007, Spain
| | - Alessandro Brunelli
- Department of Thoracic Surgery, St James's University Hospital, Leeds LS9 7TF, United Kingdom
| | - Hiran C Fernando
- Section of Thoracic Surgery, Inova Fairfax Medical Center, Inova Schar Cancer Institute, Falls Church, VA 22042, United States
| | - Robert J Cerfolio
- Department of Cardiothoracic Surgery, New York University Langone Health, New York, NY 10016, United States
| | - Mahmoud Ismail
- Department of Thoracic Surgery, Academic Hospital of the Charité–Universitätsmedizin, Humboldt University Berlin, Berlin 10117, Germany
| | - Hong Yang
- Department of Thoracic Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Esophageal Cancer Institute, Sun Yat-sen University Cancer Center, Guangzhou 510060, Guangdong Province, China
| | | |
Collapse
|
|
11
|
Jeon EY, Lee J, Kim BJ, Joo KI, Kim KH, Lim G, Cha HJ. Bio-inspired swellable hydrogel-forming double-layered adhesive microneedle protein patch for regenerative internal/external surgical closure. Biomaterials 2019; 222:119439. [PMID: 31465886 DOI: 10.1016/j.biomaterials.2019.119439] [Citation(s) in RCA: 96] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2019] [Revised: 08/17/2019] [Accepted: 08/17/2019] [Indexed: 12/21/2022]
Abstract
Significant tissue damage, scarring, and an intense inflammatory response remain the greatest concerns for conventional wound closure options, including sutures and staples. In particular, wound closure in internal organs poses major clinical challenges due to air/fluid leakage, local ischemia, and subsequent impairment of healing. Herein, to overcome these limitations, inspired by endoparasites that swell their proboscis to anchor to host's intestines, we developed a hydrogel-forming double-layered adhesive microneedle (MN) patch consisting of a swellable mussel adhesive protein (MAP)-based shell and a non-swellable silk fibroin (SF)-based core. By possessing tissue insertion capability (7-times greater than the force for porcine skin penetration), MAP-derived surface adhesion, and selective swelling-mediated physical entanglement, our hydrogel-forming adhesive MN patch achieved ex vivo superior wound sealing capacity against luminal leaks (139.7 ± 14.1 mmHg), which was comparable to suture (151.0 ± 23.3 mmHg), as well as in vivo excellent performance for wet and/or dynamic external and internal tissues. Collectively, our bioinspired adhesive MN patch can be successfully used in diverse practical applications ranging from vascular and gastrointestinal wound healing to transdermal delivery for pro-regenerative or anti-inflammatory agents to target tissues.
Collapse
Affiliation(s)
- Eun Young Jeon
- Department of Chemical Engineering, Pohang University of Science and Technology, Pohang, 37673, South Korea
| | - Jungho Lee
- Department of Mechanical Engineering, Pohang University of Science and Technology, Pohang, 37673, South Korea
| | - Bum Ju Kim
- Department of Mechanical Engineering, Pohang University of Science and Technology, Pohang, 37673, South Korea
| | - Kye Il Joo
- Department of Chemical Engineering, Pohang University of Science and Technology, Pohang, 37673, South Korea
| | - Ki Hean Kim
- Department of Mechanical Engineering, Pohang University of Science and Technology, Pohang, 37673, South Korea
| | - Geunbae Lim
- Department of Mechanical Engineering, Pohang University of Science and Technology, Pohang, 37673, South Korea.
| | - Hyung Joon Cha
- Department of Chemical Engineering, Pohang University of Science and Technology, Pohang, 37673, South Korea.
| |
Collapse
|
|
12
|
Fish Collagen Surgical Compress Repairing Characteristics on Wound Healing Process In Vivo. Mar Drugs 2019; 17:md17010033. [PMID: 30625985 PMCID: PMC6357035 DOI: 10.3390/md17010033] [Citation(s) in RCA: 79] [Impact Index Per Article: 13.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2018] [Revised: 11/16/2018] [Accepted: 11/20/2018] [Indexed: 12/21/2022] Open
Abstract
The development of biomaterials with the potential to accelerate wound healing is a great challenge in biomedicine. In this study, four types of samples including pepsin soluble collagen sponge (PCS), acid soluble collagen sponge (ACS), bovine collagen electrospun I (BCE I) and bovine collagen electrospun II (BCE II) were used as wound dressing materials. We showed that the PCS, ACS, BCE I and BCE II treated rats increased the percentage of wound contraction, reduced the inflammatory infiltration, and accelerated the epithelization and healing. PCS, ACS, BCE I, and BCE II significantly enhanced the total protein and hydroxyproline level in rats. ACS could induce more fibroblasts proliferation and differentiation than PCS, however, both PCS and ACS had a lower effect than BCE I and BCE II. PCS, ACS, BCE I, and BCE II could regulate deposition of collagen, which led to excellent alignment in the wound healing process. There were similar effects on inducing the level of cytokines including EGF, FGF, and vascular endothelial marker CD31 among these four groups. Accordingly, this study disclosed that collagens (PCS and ACS) from tilapia skin and bovine collagen electrospun (BCE I and BCE II) have significant bioactivity and could accelerate wound healing rapidly and effectively in rat model.
Collapse
|
|
13
|
Wang XH, Ni JS, Cao NL, Yu S, Chen YG, Zhang SX, Gu BJ, Yan J. In vivo evaluation of Mg-6Zn and titanium alloys on collagen metabolism in the healing of intestinal anastomosis. Sci Rep 2017; 7:44919. [PMID: 28317926 PMCID: PMC5357906 DOI: 10.1038/srep44919] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2016] [Accepted: 02/16/2017] [Indexed: 12/04/2022] Open
Abstract
There is a great clinical need for biodegradable materials, which were used as pins of circular staplers, for gastrointestinal reconstruction in medicine. In this work we compared the effects of the Mg-6Zn and the titanium alloys on collagen metabolism in the healing of the intestinal tract in vivo. The study included Sprague-Dawley rats and their effect was compared on rat's intestinal tract, using serum magnesium, radiology, and immunohistochemistry in vivo. Radiographic and scanning electron microscope evaluation confirmed the degradation by Mg-6Zn alloy during the implantation period. Biochemical measurements including serum magnesium, creatinine, blood urea nitrogen and glutamic-pyruvic-transaminase proved that degradation of Mg-6Zn alloy showed no impact on serum magnesium and the function of other important organs. Superior to titanium alloy, Mg-6Zn alloy enhanced the expression of collagen I/III and relatively suppressed the expression of MMP-1/-13 in the healing tissues, leading to more mature collagen formation at the site of anastomosis. In conclusion, Mg-6Zn alloy performed better than titanium alloy on collagen metabolism and promoted the healing of intestinal anastomosis. Hence, Mg-6Zn may be a promising candidate for use of stapler pins for intestinal reconstruction in the clinically.
Collapse
Affiliation(s)
- Xiao-hu Wang
- Department of Urology, Shanghai Sixth People’s Hospital, Shanghai Jiao Tong University, Shanghai 200233, China
| | - Jian-shu Ni
- Department of Urology, Shanghai Sixth People’s Hospital, Shanghai Jiao Tong University, Shanghai 200233, China
| | - Nai-long Cao
- Department of Urology, Shanghai Sixth People’s Hospital, Shanghai Jiao Tong University, Shanghai 200233, China
| | - Song Yu
- Department of General Surgery, Shanghai Sixth People’s Hospital, Shanghai Jiao Tong University, Shanghai 200233, China
| | - Yi-gang Chen
- Department of General Surgery, Nanjing Medical University Affiliated Wuxi No. 2 People’s Hospital, Nanjing 214002, China
| | | | - Bao-jun Gu
- Department of Urology, Shanghai Sixth People’s Hospital, Shanghai Jiao Tong University, Shanghai 200233, China
| | - Jun Yan
- Department of General Surgery, Shanghai Sixth People’s Hospital, Shanghai Jiao Tong University, Shanghai 200233, China
| |
Collapse
|