透明质酸钠预防术后粘连的研究进展

外科术后粘连一直是临床上较为常见的并发症,可导致肠梗阻、不育症和疼痛等;超声引导下甲状腺结节热消融术后,也会由于局部组织粘连引起颈部异物感、声音嘶哑、吞咽困难等。透明质酸钠因具有良好的粘弹性、生物相容性、稳定的理化性质等优势,已被广泛应用于预防外科术后粘连。本文针对透明质酸钠的物理结构、理化性质、预防术后粘连的机制以及应用进展进行综述。     

羧甲基纤维素透明质酸钠预防术后腹膜粘连的实验研究

目的 探讨羧甲基纤维素透明质酸钠复合物（CMC-HA）在腹膜粘连预防中的价值.方法 将90只Wistar大鼠分为A、B、C 3组,每组30只,制成腹膜粘连模型后分别于创面置入羧甲基纤维素（CMC）、透明质酸钠（HA）和CMC-HA各3 ml,分别于术后3 d、7 d和14 d观察腹腔粘连情况.结果 术后3 d于光镜下可见,与A组和B组相比,C组大鼠肠壁纤维细胞增生较轻,胶原纤维排列较疏松.术后14 d,C组大鼠腹膜粘连程度明显轻于A组和B组（均P＜0.01）.结论 CMC-HA预防术后腹膜粘连安全有效.     

羧甲基纤维素透明质酸钠预防术后腹膜粘连的实验研究

目的 探讨羧甲基纤维素透明质酸钠复合物(CMC-HA)在腹膜粘连预防中的价值.方法 将90只Wistar大鼠分为A、B、C 3组,每组30只,制成腹膜粘连模型后分别于创面置入羧甲基纤维素(CMC)、透明质酸钠(HA)和CMC-HA各3 ml,分别于术后3 d、7 d和14 d观察腹腔粘连情况.结果 术后3 d于光镜下可见,与A组和B组相比,C组大鼠肠壁纤维细胞增生较轻,胶原纤维排列较疏松.术后14 d,C组大鼠腹膜粘连程度明显轻于A组和B组(均P＜0.01).结论 CMC-HA预防术后腹膜粘连安全有效.     

透明质酸钠在手外伤肌腱断裂吻合术中的临床应用

近来，越来越多的手外伤造成肌腱断裂，急诊手术后对于肌腱粘连的防治，尚无有效的措施。因此，如何预防手外伤后肌腱粘连和寻求预防粘连的药物和方法是目前手外伤研究的课题之一。预防手外伤后肌腱粘连最重要的是术中精确操作，再辅以适当的防粘连的措施和术后功能锻炼，才能取得良好的结果，已有的研究表明透明质酸钠具有良好的生物相溶性，对预防和治疗术后组织粘连有良好的效果，自2002～2003年，我们对88例手外伤术后肌腱损伤修复处的鞘内或局部注射透明质酸钠预防肌腱粘连，取得良好效果。现报告如下。     

羧甲基纤维素预防术后肠粘连的实验研究

目的：探索预防腹部术后肠粘连的有效方法。方法：用大鼠肠粘连的动物模型观察可降解生物高分子材料——羧甲基纤维素预防术后肠粘连，并与透明质酸钠进行对比。结果：羧甲基纤维素能明显减轻腹部术后肠粘连的发生率，其抗粘连效果优于透明质酸钠。结论：可降解生物高分子材料——羧甲基纤维素预防腹部术后肠粘连效果满意，尤其对术后大面积、广泛粘连的预防效果更佳，其临床应用前景广阔。     

术后腹膜粘连的发病机制及预防的研究进展

腹膜粘连是腹盆腔手术、腹腔感染、肿瘤放疗后常见的病理过程，以腹膜腔内形成纤维瘢痕为标志。腹膜粘连可导致粘连性小肠梗阻等多种并发症，严重影响患者的生活质量。对近年来国内外有关腹膜粘连发病机制及预防方法的文献进行复习，为预防术后腹膜粘连提供参考。     

生物胶体液对腹部手术后粘连性肠梗阻的预防作用

目的探讨生物胶体液对预防术后粘连眭肠梗阻及促进术后胃肠功能恢复的作用。方法140例腹部手术患者随机分为研究组71例和对照组凹例，研究组术中使用生物胶体液冲洗手术区域并保留部分于腹腔内，对照组未使用，比较2组术后粘连性肠梗阻发生率和对术后胃肠功能恢复的影响。结果研究组术后粘连性肠梗阻发生率明显低于对照组，差异有统计学意义（P〈0．05），并且可促进术后胃肠功能恢复，缩短患者的住院时间（P〈0．05）。结论腹部手术中应用生物胶体液安全有效，对预防粘连性肠梗阻、促进术后胃肠功能恢复有显著作用，可作为术中的常规操作推广应用。     

硅橡胶膜防止心胸手术后粘连的研究

硅橡胶膜防止心胸手术后粘连的研究高尚志，王土生，林道明，涂仲凡，毛志福，孙有刚，姚震术后粘连既是外科领域内常见现象，也是术后愈合过程中必然发生的病理生理过程。有时，可利用这种术后粘连以产生治疗效果，但大多情况下是需要预防术后发生粘连造成并发症。本研究...     

TCRA术后Foley球囊+自交联透明质酸钠凝胶在宫腔粘连患者中的应用效果

目的探讨宫腔粘连患者宫腔镜下宫腔粘连分离术(transcervical resection of adhesions,TCRA)术后应用Foley球囊+自交联透明质酸钠凝胶预防术后再粘连的临床效果。方法选取我院在2015年12月至2017年11月收治的中重度宫腔粘连患者120例,按照随机数字表法分为观察组和对照组,每组各60例;观察组在TCRA术后应用Foley球囊+自交联透明质酸钠凝胶预防再粘连;对照组在TCRA术后应用Foley球囊+普通医用透明质酸钠凝胶预防再粘连。术后3个月观察两组患者临床疗效及AFS评分、粘连范围、粘连类型、月经状况及再粘连状况。结果治疗后观察组临床有效率为86.67%(52/60),对照组临床有效率为71.67%(43/60),比较具有统计学差异(χ2=4.093,P0.05);术后3个月宫腔镜检查两组患者AFS总分、粘连范围评分、粘连类型及月经状况评分较术前均明显下降(P0.05);观察组AFS总分、月经状况评分明显低于对照组,差异具有统计学意义(P0.05);两组患者术后粘连范围、粘连类型比较差异无统计学意义(P0.05);术后3个月宫腔镜检查,观察组术后再粘连发生率为1.92%(1/52),对照组术后再粘连发生率为16.28%(7/43),比较具有统计学差异(χ2=4.566,P0.05)。结论宫腔粘连患者TCRA术后应用Foley球囊+自交联透明质酸钠凝胶预防粘连效果显著,能够有效降低AFS评分及月经状况,值得临床推广。     

甲硝唑或右旋糖酐腹腔灌注对术后腹腔粘连影响的实验研究

用甲硝唑或右旋糖酐灌注腹腔，作术后腹腔粘连形成和腹腔粘连松解后粘连再形成的实验研究。结果表明：甲稍唑通过抗菌消炎作用具有显著预防腹腔粘连作用（Ｐ＜０．０５）。６％Ｄ７０具有显著预防术后腹腔粘连作用（Ｐ＜０．０５），６％Ｄ４０作用不可靠（一次Ｐ＜０．０５，三次Ｐ＞０．０５）。为腹腔内使用甲硝唑或右旋糖酐提供了实验依据。     

Innovation and Change in Medical Technology: Interactions Between Physicians and Engineers

Intraperitoneal adhesions following surgical procedures cause considerable morbidity. Hyaluronic acid/carboxymethylcellulose (HA/CMC) films have been shown to be effective agents in decreasing adhesion formation. However, when there is an inadvertent leak of bowel contents into the peritoneum due to incomplete anastomosis, adhesion formation about a defect in order to prevent further leakage and to promote healing of the wound is important for the prevention of morbidity and mortality. The purpose of this study was to determine if an antiadhesion film (HA/CMC) impairs these potentially beneficial adhesions to bowel anastomoses, thus predisposing them to enteric leaks with subsequent peritonitis. Sixty-four rabbits were divided in two groups, each undergoing a complete or partial (90% anastomosis to simulate anastomotic leak) large bowel anastomosis. Half of each of the above groups were treated by wrapping a HNCMC film over the anastomosis and the other half were untreated controls. These two subgroups were then further divided equally and sacrificed at either 7 or 14 days for evaluation of anastomosis integrity and strength. The average anastomtic bursting pressures did not change significantly between those groups treated with HMCMC when compared to untreated controls at 7 or 14 days or in the complete or partial anastomosis group (Student's t test). Adhesion formation to the anastomosis was not impaired in either group independent of HAKMC film application. This study suggests that while HA/CMC film has been shown to decrease adhesions in other models, healing of u rabbit colonic unastomosis even in the presence of an anastomotic defect takes place, further suggesting that the stimulus for adhesion formation can overcome the antiadhesion properties of HA/CMC. Therefore, HA/CMC is a potentially safe adjuvant for preventing postoperative intraabdominal adhesions.     

Practical Limitations of Bioresorbable Membranes in the Prevention of Intra-Abdominal Adhesions

Introduction  Intra-abdominal adhesions are a significant source of postoperative morbidity. Bioresorbable barriers composed of hyaluronic acid and carboxymethylcellulose (HA/CMC) reduce adhesion formation by physically separating injured or healing peritoneal surfaces. To assess whether the efficacy of a physical barrier can extend beyond the site of application, we evaluated the effectiveness of an HA/CMC barrier in preventing adhesions distal to the site of placement. Methods  Adhesions were induced in rats by creating peritoneal ischemic buttons on either side of a midline incision. An HA/CMC barrier (Seprafilm™ Genzyme) was intraoperatively placed either under the midline incision, unilaterally over half the ischemic buttons, or bilaterally over all ischemic buttons. Control buttons received no HA/CMC. On day 7 adhesions were scored. In similar experiments, peritoneal fluid was collected at 24 h to assess the effects of HA/CMC on tissue plasminogen activator activity. Results  Placement of HA/CMC under the midline incision did not reduce adhesion formation to distal ischemic buttons (72 ± 7%) compared to controls (80 ± 8%). Unilateral placement of HA/CMC significantly (p < 0.05) reduced adhesion formation to those ischemic buttons over which the barrier was applied (35 ± 7%) compared to both contralateral (83 ± 9%) and control (80 ± 8%) ischemic buttons. The bilateral application of HA/CMC also significantly (p < 0.05) reduced adhesion formation to all ischemic buttons compared to controls (22 ± 7% vs. 66 ± 7%, respectively). HA/CMC did not affect peritoneal tPA activity. Conclusions  Effective adhesion reduction by the physical barrier HA/CMC appears to be limited to the site of application in this rat model. Despite the presence of a bioresorbable membrane at predicted sites of adhesion formation in the peritoneal cavity, adhesions readily form to distal unprotected sites. Presented, in part, at the 49th Annual Meeting of The Society for Surgery of the Alimentary Tract, May 17–21, 2008, San Diego, CA, USA This work was supported in part, by the Smithwick Endowment Fund to the Department of Surgery at Boston University School of Medicine.     

Remote Efficacy for Two Different Forms of Hyaluronate-Based Adhesion Barriers

ABSTRACT

Background: Chemically modified sodium hyaluronate and carboxymethylcellulose (HA/CMC) membrane clinically reduces adhesion formation following surgery but was not designed for laparoscopic use. HA/CMC powder of identical chemical composition has been developed to allow for application laparoscopically. We compared the adhesion reduction efficacy of HA/CMC powder and film when applied directly to or remote from sites of surgical trauma. We also investigated the effect of the powder on wound healing. Materials and Methods: Two animal models of adhesion formation were used to evaluate efficacy: a rat peritoneal sidewall defect model and a rabbit cecal abrasion/sidewall defect model. The products were applied directly to the defect or the contralateral sidewall. Adhesions were examined seven days after surgery. In a separate study, the effect of the powder on healing was evaluated at 5, 7, and 28 days using a rat incisional wound strength model. Results: HA/CMC powder and film, when applied directly to the peritoneal defect, significantly reduced adhesions relative to the untreated control in both models. Remote applications of HA/CMC powder also reduced adhesions. In contrast, remote applications of HA/CMC film had no effect. HA/CMC powder did not significantly alter incisional wound strength at any of the timepoints tested. Conclusion: In our preclinical models, HA/CMC powder had similar adhesion reduction efficacy to HA/CMC film when applied directly to sites of trauma. In addition, HA/CMC powder reduced adhesions remote from the application site. Importantly, HA/CMC powder did not impair incisional wound healing. On the basis of these results, future investigation of HA/CMC powder is warranted.     

Tranexamic Acid and Hyaluronate/Carboxymethylcellulose Create Cell Injury

Background and Objectives:

Postoperative pelvic adhesions are associated with chronic pelvic pain, dyspareunia, and infertility. The aim of this study was to evaluate the adhesion prevention effects of tranexamic acid (TA) and hyaluronate/carboxymethylcellulose (HA/CMC) barrier in the rat uterine horn models on the basis of macroscopic and microscopic adhesion scores and histopathological as well as biochemical parameters of inflammation.

Methods:

Twenty-one Wistar rats were randomly divided into 3 groups. Ten lesions were created on the antimesenteric surface of both uterine horns by bipolar cautery. Three milliliters of 0.9% sodium chloride solution were administered in the control group. A single layer of 2 × 2 cm HA/CMC was plated in group 2. Two milliliters of TA was applied in the last group. All rats were sacrificed at postoperative day 21.

Results:

No significant difference was found among the control group, the HA/CMC group, and the TA group in terms of macro-adhesion score (P = .206) and microadhesion score (P = .056). No significant difference was found among the 3 groups in terms of inflammation score (P = .815) and inflammatory cell activity (P = .835). Malondialdehyde levels were significantly lower in the control group than in the TA group and HA/CMC group (P = .028). Superoxide dismutase and glutathione S-transferase activities were found to be higher in the control group than in the TA group (P = .005) and HA/CMC group (P = .009).

Conclusions:

TA and HA/CMC had no efficacy in preventing macroscopic or microscopic adhesion formation and decreasing inflammatory cell activity or inflammation score in our rat models. TA and HA/CMC increased the levels of free radicals and reduced the activities of superoxide dismutase and glutathione S-transferase enzymes, which act to reduce tissue injury.     

Preventing intraperitoneal adhesions with atorvastatin and sodium hyaluronate/carboxymethylcellulose: a comparative study in rats

Objectives

The aim of this study was to compare the effectiveness of atorvastatin with the sodium hyaluronate/carboxymethylcellulose (HA/CMC, Seprafilm; Genzyme; Genzyme Biosurgery Corporation, Cambridge, MA) in preventing postoperative intraperitoneal adhesion formation in rats.

Methods

Sixty Wistar rats underwent a laparotomy, and adhesions A were induced by cecal abrasion. The animals were divided into 4 groups: group 1, control A; group 2, (A + atorvastatin); group 3, (A + HA/CMC), and group 4, (A + atorvastatin + HA/CMC). The atorvastatin (groups 2 and 4) and HA/CMC (groups 3 and 4) were administered intraperitoneally before the abdominal wall was closed. After 14 days, adhesions were classified by 2 independent surgeons.

Results

The adhesion scores (mean ± standard deviation) for groups 1, 2, 3, and 4 were 2.93 ± .59, 1.85 ± 1.07, 1.80 ± .86, and 1.93 ± .70, respectively. The differences in adhesion scores among all 3 preventive groups (groups 2, 3, and 4) were statistically significant when compared with the control group (P = .005, P = .002, and P = .009, respectively).

Conclusions

These data suggest that atorvastatin, administered intraperitoneally, is as effective as HA/CMC without an expectable additive effect in preventing postoperative adhesions in rats.     

Effect of prosthetic material on adhesion formation after laparoscopic ventral hernia repair in a porcine model

Intraperitoneal placement of prosthetic mesh causes adhesion formation after laparoscopic incisional hernia repair. A prosthesis that prevents or reduces adhesion formation is desirable. In this study, 21 pigs were randomized to receive laparoscopic placement of plain polypropylene mesh (PPM), expanded polytetrafluoroethylene (ePTFE), or polypropylene coated on one side with a bioresorbable adhesion barrier (PPM/HA/CMC). The animals were sacrificed after 28 days and evaluated for adhesion formation. Mean area of adhesion formation was 14% (SD±15) in the PPM/HA/CMC group, 40% (SD±17) in the PPM group, and 41% (SD±39) in the ePTFE group. The difference between PPM/HA/CMC and PPM was significant (P=0.013). A new visceral layer of mesothelium was present in seven out of seven PPM/HA/CMC cases, six out of seven PPM cases, and two out of seven ePTFE cases. Thus, laparoscopic placement of PPM/HA/CMC reduces adhesion formation compared to other mesh types used for laparoscopic ventral hernia repairs.This work was presented as an oral presentation at the American Hernia Society Meeting, Tucson, Ariz. USA in May, 2002.This study was funded by a grant from Genzyme, Corp., Cambridge, Mass. USA     

Current strategies and future perspectives for intraperitoneal adhesion prevention

INTRODUCTION: The formation of peritoneal adhesions still is a relevant clinical problem after abdominal surgery. Until today, the most important clinical strategies for adhesion prevention are accurate surgical technique and the physical separation of traumatized serosal areas. Despite a variety of barriers which are available in clinical use, the optimal material has not yet been found. DISCUSSION: Mesothelial cells play a crucial physiological role in friction less gliding of the serosa and the maintenance of anantiadhesive surface. The formation of postoperative adhesions results from a cascade of events and is regulated by various cellular and humoral factors. Therefore, optimization or functionalization of barrier materials by developments interacting with this cascade on a structural or pharmacological level could give an innovative input for future strategies in peritoneal adhesion prevention. For this purpose, the proper understanding of the formal pathogenesis of adhesion formation is essential. Based on the physiology of the serosa and the pathophysiology of adhesion formation, the available barriers in current clinical practice as well as new innovations are discussed in the present review.     

Hyaluronic acid/carboxymethylcellulose membrane barrier versus taurolidine for the prevention of adhesions to polypropylene mesh

BACKGROUND: A hyaluronic acid/carboxymethylcellulose (HA/CMC) membrane is an effective measure to prevent polypropylene mesh induced adhesions. We hypothesized that taurolidine 2% solution might be a cost-effective alternative to decrease adhesion formation. MATERIALS AND METHODS: Twenty-four rats were randomized into three groups: mesh alone (group 1), mesh + taurolidine 2% (group 2), and mesh + HA/CMC (group 3). Polypropylene mesh (4 cm2) was used to repair surgically induced anterior abdominal wall defects. Taurolidine 2%or a HA/CMC membrane was used as an antiadhesive measure. The animals were sacrificed 6 weeks after the operation, and adhesions to the prosthetic material were evaluated with digital image analysis. RESULTS: Group 1 (mesh alone) had the highest adhesion ratio (58.5 +/- 4.8%) compared with groups 2 and 3 (p < 0.05). The differences between groups 2 (mesh + taurolidine 2%; adhesion ratio 42.9 +/- 1.6%) and 3 (mesh + HA/CMC; adhesion ratio 40.3 +/- 3.0%) were not significant (p > 0.05). CONCLUSIONS: The animals of both treatment groups (2 and 3) had lower adhesion ratios compared with the controls (group 1). In particular, the HA/CMC membrane did not present with a superior antiadhesive effect compared with taurolidine. Therefore, taurolidine is a cost-effective alternative to HA/CMC membranes when a polypropylene mesh is used in direct contact with the abdominal viscera.     

Polyanionic polysaccharides reduce intra-abdominal adhesion and abscess formation in a rat peritonitis model.

BACKGROUND: Intra-abdominal infection is complicated by adhesion and abscess formation. We have assessed the adhesion- and abscess-reducing capacity of various solution volumes and concentrations of two polyanionic polysaccharides, hyaluronan (HA) and carboxymethylcellulose (CMC), in a rat peritonitis model. STUDY DESIGN: In 192 male Wistar rats a bacterial peritonitis was induced using cecal ligation and puncture. After 24 h the abdomen was reopened and the ligated cecum resected. Animals were randomized into three control groups, nine groups treated with various solution volumes (1 to 8 ml) containing different HA concentrations, and four groups treated with 1.7% CMC solution. Rats were killed at day 7, postoperatively, and adhesions were scored at five abdominal sites on a scale from 0 to 4. The presence and size of intra-abdominal abscesses were noted. RESULTS: Fifty-four rats (28%) prematurely died. There was no significant difference in mortality between treatment groups and controls. Treatment with CMC (P < 0.001) and low (0.2 and 0.4%) concentrations of HA (P < 0.005) significantly reduced intra-abdominal adhesion formation. High volumes of 0.2 and 0.4% HA were most effective (P = 0.01). The effect of CMC was volume independent. The incidence of abdominal abscesses was also significantly reduced by treatment with either CMC (P < 0.001) or low concentrations of HA (P < 0.001). With regard to abscess formation the effect was independent of the volume administered for HA, while low volumes of CMC were most effective (P < 0.005). CONCLUSION: Intraperitoneal treatment with either CMC or low-viscosity HA solution reduced intra-abdominal adhesion and abscess formation in a rat peritonitis model. The volume-induced reduction in adhesion formation suggests a hydroflotation effect of HA solution.     

Effects of hyaluronic acid/Carboxymethylcellulose gel on bowel anastomoses in the New Zealand white rabbit

Intra-abdominal adhesions form in more than 90% of patients undergoing major abdominal surgery and can lead to significant complications. Application of a bioresorbable gel consisting of chemically modified hyaluronic acid (HA) and carboxymethylcellulose (CMC) has shown promise as a means of preventing intra-abdominal adhesions, but there have been concerns that the presence of the gel might interfere with the integrity and healing of bowel anastomoses. We tested the effects of HA/CMC gel on adhesion formation and anastomotic healing in 60 New Zealand white rabbits after transection and complete (100%) or incomplete (90%) anastomosis of the ileum. Half of the animals underwent application of HA/CMC gel and half served as control subjects. Animals were killed at 4, 7, or 14 days after surgery. Anastomotic adhesions were scored in a blinded fashion. Integrity of the anastomosis was tested by measuring bursting pressure at the anastomotic site and in an adjacent section of intact bowel. With complete anastomosis, HA/CMC gel significantly reduced adhesion formation at 7 and 14 days after surgery (P<0.05), but gel application did not inhibit adhesion formation when the anastomosis was incomplete. Anastomosed segments of bowel burst at a lower pressure than intact bowel 4 days after surgery, but bursting pressures were normal at 7 and 14 days. Burst pressures of anastomoses receiving an application of HA/CMC gel were nearly identical to control anastomoses at all three time points. HA/CMC gel did not interfere with the normal healing process of bowel anastomoses. Furthermore, HA/CMC gel decreased adhesion formation after complete anastomoses, yet it did not affect adhesion formation in the presence of anastomotic disruption.