Hyaluronate-based Bioresorbable Membrane Research Articles

SP10.1.6 Effect of hyaluronate-based bioresorbable membrane (Seprafilm) on outcomes of abdominal surgery: a meta-analysis and trial sequential analysis of randomised controlled trials

Abstract Background We aimed to evaluate comparative outcomes of abdominal surgery with and without hyaluronate-based bioresorbable membrane (Seprafilm). Methods We conducted a systematic search of electronic databases and bibliographic reference lists with application of a combination of free text and controlled vocabulary search adapted to thesaurus headings, search operators and limits. Small bowel obstruction, anastomotic leak, surgical site infections, ileus, and severity of adhesions were the evaluated outcome measures. Results Thirteen randomised controlled trials reporting a total of 3,665 patients evaluating outcomes of abdominal surgeries with (n=1,800) or without (n=1,865) use of Seprafilm were identifed. Use of Seprafilm was associated with significantly lower risk of small bowel obstruction (RR:0.53, 95% CI 0.38–0.73, P=0.0001) but significantly higher rate of anastomotic leak (RR: 1.85, 95% CI 1.15–3.00 P=0.01). Moreover, while Seprafilm resulted in significantly more adhesions-free patients (RR:5.57, 95% CI 3.37–9.19, P<0.0001) compared to no Seprafilm, its use was associated with significantly lower grade 2 (RR:0.57, 95% CI 0.35–0.95, P=0.003) or 3 (RR:0.31, 95% CI 0.17–0.55, P<0.0001) adhesions. There was no significant difference in surgical site infection (RR:1.21, 95 CI 0.86–1.70, P=0.28), intra-abdominal abscess (RR: 1.46, 95 CI 0.92–2.32, P=0.11) or paralytic ileus (RR:0.97, 95 CI 0.68–1.38, P=0.87) between two groups. The trial sequential analysis demonstrated that the meta-analysis findings are conclusive. Conclusions Seprafilm reduces the risk of small bowel obstruction and severity of adhesions after abdominal surgery. However, it may increase the risk of anastomotic leak. We recommend use of Seprafilm in any abdominal surgery which does not involve an anastomosis.

Effect of hyaluronate-based bioresorbable membrane (Seprafilm) on outcomes of abdominal surgery: a meta-analysis and trial sequential analysis of randomised controlled trials.

We aimed to evaluate comparative outcomes of abdominal surgery with and without hyaluronate-based bioresorbable membrane (Seprafilm).We conducted a systematic search of electronic databases and bibliographic reference lists with application of a combination of free text and controlled vocabulary search adapted to thesaurus headings, search operators and limits. Small bowel obstruction, anastomotic leak, surgical site infections, ileus, and severity of adhesions were the evaluated outcome measures. Thirteen randomised controlled trials reporting a total of 3665 patients evaluating outcomes of abdominal surgeries with (n = 1800) or without (n = 1865) use of Seprafilm were identified. Use of Seprafilm was associated with significantly lower risk of small bowel obstruction (RR 0.53, 95% CI 0.38-0.73, P = 0.0001) but significantly higher rate of anastomotic leak (RR 1.85, 95% CI 1.15-3.00 P = 0.01). Moreover, while Seprafilm resulted in significantly more adhesions-free patients (RR 5.57, 95% CI 3.37-9.19, P < 0.0001) compared to no Seprafilm, its use was associated with significantly lower grade 2 (RR 0.57, 95% CI 0.35-0.95, P = 0.003) or 3 (RR 0.31, 95% CI 0.17-0.55, P < 0.0001) adhesions. There was no significant difference in surgical site infection (RR: 1.21, 95 CI 0.86-1.70, P = 0.28), intra-abdominal abscess (RR 1.46, 95 CI 0.92-2.32, P = 0.11) or paralytic ileus (RR 0.97, 95 CI 0.68-1.38, P = 0.87) between two groups. The trial sequential analysis demonstrated that the meta-analysis findings are conclusive. Our meta-analysis demonstrated that Seprafilm reduces the risk of small bowel obstruction and severity of adhesions after abdominal surgery. However, it may increase the risk of anastomotic leak. We recommend use of Seprafilm in any abdominal surgery which does not involve an anastomosis.

Is liquid-based hyaluronic acid equivalent to sodium hyaluronate-based bioresorbable membrane to reduce small bowel obstruction in patients undergoing colorectal surgery

We performed a prospective randomized study to assess whether the use of sodium hyaluronate-based bioresorbable membrane (Seprafilm®) and liquid-based hyaluronic acid and carboxymethyl cellulose solution (Guardix) to reduce postoperative small bowel small bowel obstruction in patients undergoing colorectal surgery. This study aimed to compare the incidence of postoperative bowel obstruction. One hundred seven patients were assigned to the Seprafilm® group and 155 were assigned to the Guardix® group during the study period. The control group of 166 patients received no anti-adhesive. Patients were randomly assigned. The overall small bowel obstruction rate was 7.6% (N=37/488 patients). Small bowel obstruction developed in 9 patients (5.8%) in the Guardix® group and 9 patients (7.1%) in the Seprafilm® group and 19 patients (11.4%) in the control group. Seprafilm® group had significantly lower obstruction rate as compared to control group (P=0.036). Guardix® solution and Seprafilm® did not alter the liver and renal function, as assessed by the blood chemistry. The use of Seprafilm significantly reduces the incidence of postoperative small bowel obstruction in patients undergoing colorectal surgery. We observed no difference in the incidence of postoperative small bowel obstruction after the application of Seprafilm® and Guardix® in patients undergoing colorectal surgery.

Evaluation of the xenobiotic reaction against hyaluronate-based bioresorbable membrane in the abdominal cavity

Postoperative abdominal adhesions are one of the most common post-laparotomy complications observed. Several types of adhesion preventative agents are available and their effectiveness and adverse impact have been clinically evaluated in previous studies. However, few basic studies have tested whether those agents do not trigger any unwanted xenobiotic reaction, which makes some surgeons hesitant to use them. To clarify this point, we investigated whether the adhesion preventative agent Seprafilm® (KAKEN PHARMACEUTICAL CO., LTD., Tokyo, Japan), one of the most widely used hyaluronate-based bioresorbable membrane (HBBM), can trigger an inflammatory response in normal abdominal tissue and delay the healing process. The rat underwent laparotomy and a HBBM was placed directly below the incision. Tissue samples at the incision and away from the incision (normal tissue) were harvested and inflammatory response and fibrosis were evaluated using quantitative PCR and histological scoring. We found that HBBM did not induce inflammatory cytokine expression at mRNA level in the peritoneal wall tissue or modify the fibrosis process in the abdominal cavity. These findings confirm the safety of using HBBM for the prevention of adhesion development post-laparotomy.

Direct comparison of Seprafilm® versus Adept® versus no additive for reducing the risk of small-bowel obstruction in colorectal cancer surgery

To assess the effectiveness of using sodium hyaluronate-based bioresorbable membrane (Seprafilm(®)) versus 4 % icodextrin solution (Adept(®)) versus no additive intraoperatively and to prevent postoperative small-bowel obstruction in patients undergoing colorectal cancer (CRC) surgery. The subjects of this retrospective study were 454 patients, who underwent CRC surgery between February 2007 and January 2010. Among the 454 enrolled patients, 114 patients received Seprafilm(®), 180 patients received Adept(®), and 160 patients received no additive, based on the year of their surgery. The overall incidences of small-bowel obstruction were 8.8, 4.3, and 6.9 %, for the Adept(®), Seprafilm(®), and no additive (control) groups, respectively. The cumulative incidence was significantly higher in the Adept(®) group than in the Seprafilm(®) and control groups (Adept(®) vs. Seprafilm(®), P = 0.043; Adept(®) vs. control group, P = 0.002). No significant difference was found between the Seprafilm group and the control group (P = 0.549). Adept(®) solution and Seprafilm(®) did not alter the liver and renal function, as assessed by blood chemistry. The use of Adept(®) significantly increased the incidence of small-bowel obstruction in patients undergoing CRC surgery.

Sterile Intra-Abdominal Fluid Collection Associated with Seprafilm Use

Postoperative abdominal adhesions are a significant cause of morbidity and expenditure of healthcare resources. As a result, numerous substances have been studied in an effort to reduce the incidence of adhesive disease. Seprafilm, a hyaluronate-based bioresorbable membrane, has been the subject of considerable research and has been found to be both safe and effective in reducing postoperative adhesions. We report three cases of the development of sterile abdominal fluid collection after the use of Seprafilm in colorectal surgery.

Sodium hyaluronate-based bioresorbable membrane (Seprafilm®) reduced early postoperative intestinal obstruction after lower abdominal surgery for colorectal cancer: the preliminary report

This study is a prospective randomized clinical trial to evaluate the clinical safety and the effect of a sodium hyaluronate-based bioresorbable membrane (Seprafilm; Genzyme, Cambridge, MA, USA) for reducing adhesive intestinal obstruction after colorectal cancer surgery. Between November 2002 and December 2003, 504 patients underwent radical resection for sigmoid or rectal cancer. Among these patients, 427 patients were enrolled in this study. The patients were randomized into the Seprafilm group (N = 185) and the control group (N = 242). All the patients in the Seprafilm) group received one sheet of Seprafilm over the pelvic inlet where the peritoneum was denuded due to pelvic dissection. Intestinal obstruction was defined when there were symptoms of nausea, vomiting, and abdominal distension combined with an obstructive bowel pattern on the radiologic evaluation. The median follow-up period was 25.0 months. There were no significant differences between the Seprafilm and the control groups for the clinicopathologic parameters. There were no differences in the incidence of complications between the two groups; however, the incidence of early postoperative intestinal obstruction was significantly less in the Seprafilm group than in the control group (2.7% vs 7.0%, respectively, p = 0.045). Five patients in the Seprafilm group experienced postoperative intestinal obstruction (2.7%) compared with 11 patients in the control group (4.6%) during the follow-up period; however, there was no statistical difference. Seprafilm appears to be effective in preventing early postoperative intestinal obstruction and there was a trend for reduced intestinal obstruction after lower abdominal surgery for colorectal cancer.

Bioresorbable Membrane to Reduce Postoperative Small Bowel Obstruction in Patients With Gastric Cancer

This randomized controlled trial was designed to assess whether the use of a sodium hyaluronate-based bioresorbable membrane reduces small bowel obstruction after gastrectomy for gastric cancer. Clinical studies have reported that a bioresorbable membrane significantly reduces the incidence and severity of adhesion after abdominopelvic surgery. Between 2003 and 2006, a total of 150 patients with gastric cancer who were scheduled to undergo gastrectomy were randomly assigned to a sodium hyaluronate-based bioresorbable membrane (Seprafilm) group or to a control group. Before closing the abdominal incision, 2 sheets of Seprafilm membrane were applied to the surface of the small intestine under the middle abdominal wound in the Seprafilm group. The primary end point was the incidence of bowel obstruction. Secondary end points were intraoperative and postoperative morbidity and mortality. We registered with Clinical Trials.gov using the Protocol Registration System (ID-NCT00529412). We evaluated a total of 144 patients: 70 in the Seprafilm group and 74 in the control group. The overall incidence (Seprafilm group, 5.7% vs. control group, 9.5%; P = 0.534) and the cumulative incidence of small bowel obstruction (6.2% vs. 12.2% at 36 months; P = 0.3789) were slightly but not significantly lower in the Seprafilm group. The incidence of postoperative complications was similar in the groups (32.9% vs. 29.7%; P = 0.722). Seprafilm did not adversely affect bowel, liver, or renal functions. The use of Seprafilm does not significantly reduce the incidence of small bowel obstruction in patients undergoing gastrectomy for gastric cancer.

Preservation of the mastoid aeration and prevention of mastoid dimpling in chronic otitis media with cholesteatoma surgery using hyaluronate-based bioresorbable membrane (Seprafilm)

During mastoidectomy a hollow-cavity is formed within the mastoid bone after its cortex and air cells are removed. Postoperatively, the aerated cavity is usually filled with soft tissues. Also it is not so uncommon to see cases with retraction of the mastoid area skin into the cavity causing a cosmetic problem termed as mastoid dimpling. In order to achieve an aerated mastoid cavity and minimizing the mastoid dimpling, an adhesion barrier was utilized to prevent fibrous tissue formation within the cavity. Twenty-one patients with middle ear and/or mastoid cholesteatoma, who underwent tympanoplasty with mastoidectomy (canal wall-up) with staged procedures, were included in the study. The mastoid cavity was tented and covered with an adhesion barrier (hyaluranic acid and carboxymethylcellulose, Seprafilm, (Seprafilm, GENZYME Inc., Cambridge, MA, USA) at the end of the surgery. Postoperatively, in two cases serohemorrhagic fluid collected between the adhesion barrier membrane and the subcutaneous tissues requiring drainage. Second stages were performed 4-6 months after the first stage. Two residual cholesteatoma cases were present. Patients were followed for a minimum of 2 years after the second stage. Mean follow-up was 2 years and 5 months. No wound infection was encountered postoperatively. Late follow-up of minimum 2 years after the second surgery revealed cosmetically acceptable retroauricular area with no dimpling. Mild retraction in two cases and two micro-central perforations in the neotympanic membrane were found. CT scans obtained both prior to the second stage and at the end of the second year of second stage revealed fully aerated mastoid cavities covered with periosteum in its natural position. Mastoid cortex plasty with seprafilm offers a rapid and effective solution to the preservation of mastoid space and the preservation of the contours of the mastoid bone.

Protection of trocar sites from gallbladder cancer implantation by sodium hyaluronate carboxymethylcellulose-based bioresorbable membrane (Seprafilm) in a murine model [corrected

The risk of port site metastasis in laparoscopic surgery for cancer patients is a problem that has yet to be resolved. We examined the protective effect of a sodium hyaluronate-based bioresorbable membrane (Seprafilm) on tumor cell implantation at laparoscopic trocar sites. Four 2-mm trocar sites were created in nude mice, and the peritoneal wounds were covered with different-sized pieces of Seprafilm. The protective effect of Seprafilm on the implantation of GB-d1 (a human gallbladder cancer cell line) at the trocar sites was assessed after 7 days. In addition, the effects of sodium hyaluronate and Seprafilm on the growth and motility of GB-d1 were examined in vitro. Seprafilm significantly decreased the incidence of implantation compared with the control group. Histologically, Seprafilm was observed on days 1 and 3, as a sheet of gel that covered the injured peritoneum and muscle layer. In an invasion assay using Seprafilm, no cells were found to infiltrate through the gel sheet. Seprafilm protects peritoneal wounds by physically covering the injured peritoneum. Therefore, if Seprafilm were attached to the injured peritoneum after laparoscopic surgery for cancer patients, it might reduce port site metastasis.

An Unusual Complication after Hyaluronate-Based Bioresorbable Membrane (Seprafilm) Application

Recent developments in adhesion prevention have led to the introduction of a sodium hyaluranate-based bioresorbable membrane into clinical practice. Its application has been regarded as safe and efficient. We present three cases of postoperative acute aseptic peritonitis without an obvious etiology, which might have been related to this bioresorbable membrane during recent surgery. Surgeons should be aware of this kind of a complication that might be attributed to this product.

Prevention of intraabdominal adhesions in Kasai portoenterostomy

An infant with biliary atresia had the right side of his liver covered with a sodium hyaluronate-based bioresorbable membrane during his initial Kasai portoenterostomy procedure. When his peritoneal cavity was entered 10.6 months (317 days) later for a liver transplant operation there was a remarkable absence of intraabdominal adhesions leading to a smooth operation and an uncomplicated recovery. J Pediatr Surg 36:1613-1614. Copyright © 2001 by W.B. Saunders Company.

Sodium hyaluronate carboxymethylcellulose-based bioresorbable membrane (Seprafilm)--does it affect tumor implantation at abdominal wound sites?

This study examines the effects of a sodium hyaluronate-based bioresorbable membrane (Seprafilm) on tumor implantation at surgical wound and laparoscopic trocar sites. GW-39, an established human colon cancer line carried in immunocompetent golden Syrian hamsters was used as the experimental model. Under general anesthesia, a 2-cm midline incision was made to allow placement of four 5-mm abdominal trocars. Hamsters were then randomly assigned to preSeprafilm, postSeprafilm, and control (no Seprafilm) groups. In the preSeprafilm group 0.5 ml of a 5 percent (vol/vol) suspension of the GW-39 tumor cells (approximately 1.675 x 10(6) cells) was injected into the abdomen of each hamster via midline incision. Trocars were removed, the wounds were closed, and 1 cm2 of Seprafilm was placed on the peritoneal surface of each trocar site. In the postSeprafilm group the membrane was placed at each site before injection of tumor cells. The control group did not receive Seprafilm. The animals were killed after seven weeks, and the abdominal wound sites were excised. Sites without gross tumor underwent histologic evaluation. One hundred thirty-two animals were randomly assigned to the three groups. The preSeprafilm group had an 87 percent tumor implantation rate. The postSeprafilm group had a 90 percent tumor implantation rate. The control group had an 88 percent tumor implantation rate. Chi squared analysis demonstrated that these total tumor implant rates and mean tumor mass were similar at all wound sites and between groups. No toxicity was observed in any of the experimental groups. Sodium hyaluronate-based bioresorbable membrane (Seprafilm) does not influence GW-39 human colon cancer implantation at abdominal wound sites in this hamster model.