Prevention of postoperative abdominal adhesions by a sodium hyaluronate-based bioresorbable membrane: a prospective, randomized, double-blind multicenter study. Fewer intraperitoneal adhesions with use of hyaluronic acid-carboxymethylcellulose membrane: a randomized clinical trial. A randomized controlled trial of 0.5% ferric hyaluronate gel (Intergel) in the prevention of adhesions following abdominal surgery. Prevention of postoperative abdominal adhesions by a novel, glycerol/sodium hyaluronate/carboxymethylcellulose-based bioresorbable membrane: a prospective, randomized, evaluator-blinded multicenter study. Comparison of J-pouch and coloplasty pouch for low rectal cancers: a randomized, controlled trial investigating functional results and comparative anastomotic leak rates. Bioresorbable adhesion barrier facilitates early closure of the defunctioning ileostomy after rectal excision: a prospective, randomized trial. Initial feasibility study of a sprayable hydrogel adhesion barrier system in patients undergoing laparoscopic ovarian surgery. Effect of intraoperative fluid administration and colloid osmotic pressure on the formation of intestinal edema during gastrointestinal surgery. A randomized, prospective, controlled, multicenter clinical trial of a sprayable, site-specific adhesion barrier system in patients undergoing myomectomy.
Postoperative abdominal adhesions are associated with numerous complications, including small bowel obstruction, difficult and dangerous reoperations, and infertility. A sodium hyaluronate and carboxymethylcellulose bioresorbable membrane (HA membrane) was developed to reduce formation of postoperative adhesions. The objectives of our prospective study were to assess the incidence of adhesions that recurred after a standardized major abdominal operation using direct laparoscopic peritoneal imaging and to determine the safety and effectiveness of HA membrane in preventing postoperative adhesions.
                Eleven centers enrolled 183 patients with ulcerative colitis or familial polyposis who were scheduled for colectomy and ileal pouch-anal anastomosis with diverting-loop ileostomy. Before abdominal closure, patients were randomly assigned to receive or not receive HA membrane placed under the midline incision. At ileostomy closure eight to 12 weeks later, laparoscopy was used to evaluate the incidence, extent, and severity of adhesion formation to the midline incision.
                Data were analyzed for 175 assessable patients. While only five (6 percent) of 90 control patients had no adhesions, 43 (51 percent) of 85 patients receiving HA membrane were free of adhesions (p < 0.00000000001). The mean percent of the incision length involved was 63 percent in the control group, significantly greater than the 23 percent observed in patients who received HA membrane (p < 0.001). Dense adhesions were observed in 52 (58 percent) of the 90 control patients, but in only 13 (15 percent) of the 85 receiving HA membrane (P < 0.0001). Comparison of the incidence of specific adverse events between the groups did not identify a difference (P > 0.05).
                This study represents the first controlled, prospective evaluation of postoperative abdominal adhesion formation and prevention after general abdominal surgery using standardized, direct peritoneal visualization. In this study, HA membrane was safe and significantly reduced the incidence, extent, and severity of postoperative abdominal adhesions. To assess the effectiveness of bioresorbable Seprafilm membrane in preventing abdominal adhesions in a prospective clinical randomized multicenter trial.
                Adhesions occur frequently after abdominal operations and are a common cause of bowel obstruction, chronic abdominal pain, and infertility. To reduce the formation of adhesions, a mechanical barrier composed of hyaluronic acid and carboxymethylcellulose was developed, preventing adherence of tissues after abdominal surgery.
                Between April 1996 and September 1998, all patients requiring a Hartmann procedure for sigmoid diverticulitis or obstructed rectosigmoid were randomized to either intraperitoneal placement of the antiadhesions membrane under the midline during laparotomy and in the pelvis, or as a control. Direct visual evaluation of the incidence and severity of adhesions was performed laparoscopically at second-stage surgery for restoration of the continuity of the colon.
                A total of 71 patients were randomized; of these, 42 could be evaluated. The incidence of adhesions did not differ significantly between the two groups, but the severity of adhesions was significantly reduced in the Seprafilm group both for the midline incision and for the pelvic area. Complications occurred in similar numbers in both groups.
                Seprafilm antiadhesions membrane appears effective in reducing the severity of postoperative adhesions after major abdominal surgery, although the incidence of adhesions was not diminished. The authors recommend using Seprafilm when relaparotomy or second-look intervention is planned. Long-term studies are needed to assess the cost-effectiveness and value of Seprafilm in preventing bowel obstruction, chronic abdominal pain, and infertility. Intestinal adhesion following abdominal surgery is a significant sequela to abdominal surgery. Intergel is a hyaluronate-based gel that reduces the incidence of postoperative adhesions when added to the peritoneal cavity before closure in gynecologic surgery. This is a randomized controlled trial evaluating the efficacy and safety of Intergel in colorectal resections. Although the study aimed to recruit 200 patients based on power analysis, recruitment was suspended because of the high morbidity in the treatment group.
                A total of 32 patients were randomized to either Intergel treatment (treatment group) or no treatment (control group) following open abdominal surgery. Primary endpoints included the incidence of adhesive obstruction, the need for subsequent adhesiolysis, and the incidence of wound and anastomotic complications. A secondary endpoint involved quality-of-life assessment.
                Seventeen patients were randomized to the treatment group and 15 to the control group. All patients, except 1 in the treatment group, underwent resection and anastomosis of the colon or rectum for benign or malignant disease. A significant difference was observed in the number of patients with postoperative morbidities between the 2 groups (65% treatment group versus 27% control group, P = 0.031). There was a high rate of anastomotic dehiscence (5 treatment group versus 1 control group, P = 0.178) and prolonged postoperative ileus (10 treatment group versus 2 control group, P = 0.011) observed in treatment group. One case of peritonitis occurred in the treatment group in the presence of an intact anastomosis. Wound complications were more common in treatment group but failed to reach statistical significance.
                The use of Intergel in abdominal surgery where the gastrointestinal tract is opened leads to unacceptably high rates of postoperative complications. Postoperative abdominal adhesions are associated with significant morbidity and mortality, placing a substantial burden on healthcare systems worldwide. Development of a bioresorbable membrane containing up to 23 percent glycerol and chemically modified sodium hyaluronate/carboxymethylcellulose offers ease of handling and has been shown to provide significant postoperative adhesion prevention in animals. This study was designed to assess the safety of glycerol hyaluronate/carboxymethylcellulose and to evaluate its efficacy in reducing the incidence, extent, and severity of postoperative adhesion development in surgical patients.
                Twelve centers enrolled 120 patients with ulcerative colitis or familial polyposis who were scheduled for a restorative proctocolectomy and ileal pouch-anal anastomosis with diverting loop ileostomy. Before surgical closure, patients were randomized to no anti-adhesion treatment (control) or treatment with glycerol hyaluronate/carboxymethylcellulose membrane under the midline incision. At ileostomy closure, laparoscopy was used to evaluate the incidence, extent, and severity of adhesion formation to the midline incision.
                Data were analyzed using the intent-to-treat population. Treatment with glycerol hyaluronate/carboxymethylcellulose resulted in 19 of 58 patients (33 percent) with no adhesions compared with 6 of 60 adhesion-free patients (10 percent) in the no treatment control group (P = 0.002). The mean extent of postoperative adhesions to the midline incision was significantly lower among patients treated with glycerol hyaluronate/carboxymethylcellulose compared with patients in the control group (P < 0.001). The severity of postoperative adhesions to the midline incision was significantly less with glycerol hyaluronate/carboxymethylcellulose than with control (P < 0.001). Adverse events were similar between treatment and no treatment control groups with the exception of abscess and incisional wound complications were more frequently observed with glycerol hyaluronate/carboxymethylcellulose.
                Glycerol hyaluronate/carboxymethylcellulose was shown to effectively reduce adhesions to the midline incision and adhesions between the omentum and small bowel after abdominal surgery. Safety profiles for the treatment and no treatment control groups were similar with the exception of more infection complications associated with glycerol hyaluronate/carboxymethylcellulose use. Animal models did not predict these complications. To assess the efficacy of a novel coloplasty colonic pouch design in optimizing bowel function after ultralow anterior resection.
                A colonic J-pouch may reduce excessive stool frequency and incontinence after anterior resection, but at the risk of evacuation problems. Experimental surgery on pigs has suggested that a coloplasty pouch (CP) may be a useful alternative. Although CP has recently been shown to be feasible in patients, there is no randomized controlled trial comparing bowel function with the J-pouch.
                After anterior resection for cancer, patients were allocated to either J-pouch or CP-anal anastomoses. Continence scoring, anorectal manometry, and endoanal ultrasound assessments were made before surgery. All complications were recorded, and these preoperative assessments were repeated at 4 months. The assessments were repeated again at 1 year, and a quality of life questionnaire was added.
                Eighty-eight patients were recruited from October 1998 to April 2000. Both groups were well matched for age, gender, staging, adjuvant therapy, and mean follow-up. There were no differences in the intraoperative time and hospital stay. CP resulted in more anastomotic leaks. At 4 months, J-pouch patients had 10.3% less stool fragmentation but poorer stool deferment and more nocturnal leakage. However, there were no differences in the bowel function, continence score, and quality of life at 1 year. There were no differences in the anorectal manometry and endoanal ultrasound findings.
                Coloplasty pouches resulted in more anastomotic leaks and minimal differences in bowel function. At present, the J-pouch remains the benchmark for routine clinical practice, and due care (including defunctioning stoma) should be exercised in situations requiring CP. A temporary loop ileostomy is often created to minimize the impact of peritoneal sepsis from an anastomotic dehiscence after a coloanal or low colorectal anastomosis. Such a stoma is usually closed after 6 to 12 weeks when the intestinal edema is reduced and the peristomal adhesions are less dense. This period is three to four times longer than necessary for assurance of anastomotic healing, which is usually achieved by the second week after surgery. With the use of a bioresorbable membrane to minimize the formation of peristomal adhesions, earlier closure is hypothetically possible at three weeks.
                Patients undergoing creation of a defunctioning ileostomy were randomized in Phase I either to have an adhesion barrier membrane wrapped around the limbs of the ileostomy, with closure at three weeks, or to the control group, with no barrier membrane and closure after more than six weeks. In the subsequent Phase II, the efficacy of the barrier membrane was compared in a similar manner with a control group at ileostomy reversal after three weeks. Peristomal adhesions at the time of stomal mobilization were scored in a blinded manner.
                In Phase I, no statistically significant differences were noted in the mean adhesion scores between the two groups (7.42 vs. 7.28). However, in Phase II, when peristomal adhesions at closure were compared at three weeks for both groups, with and without adhesion barrier placement, there was a significant reduction in the overall mean adhesion scores (5.81 vs. 7.82, respectively). The number of patients with dense adhesions was also reduced in the adhesion barrier group. There was no significant difference in the time taken and the difficulty encountered during ileostomy closure in the two groups. A tendency to easier closure, as evidenced by a lower incidence of perioperative complications, was noted in the adhesion barrier group.
                An adhesion barrier membrane placed around the limbs of a defunctioning loop ileostomy reduces peristomal adhesion and facilitates early closure at three weeks with minimal complications. To assess the safety and effectiveness of SprayGel as a barrier to reduce the frequency of adhesion formation and reformation after ovarian surgery, and to determine the feasibility of the study design for a larger, multicenter pivotal trial.
                Prospective, randomized, internally controlled trial (Canadian Task Force classification I).
                Two metropolitan, academic-affiliated, nonprofit hospitals.
                Fourteen women.
                Bilateral adnexal surgery.
                On completion of surgery, one adnexa was randomized to receive optimal surgical treatment plus application of the adhesion barrier, and the contralateral one to receive optimal surgical treatment alone. Patients returned in 3 to 16 weeks for second-look laparoscopy. All initial and second-look procedures were videotaped and reviewed by a blinded surgeon reviewer, and assessed for frequency, extent, and severity of adhesions. The frequency and extent of adhesion formation at second-look laparoscopy were statistically reduced on treatment sides compared with control sides (71% reduction in frequency, p = 0.0488; 69% reduction in extent, p = 0.0494). Adhesion severity score was reduced by 43% on the treatment side. SprayGel was associated with no adverse effects and was applied successfully in all patients.
                This material shows great promise in preventing postoperative adhesion formation in a population of patients greatly in need of such an adjunct. These findings warrant a larger, pivotal, multicenter study to evaluate SprayGel further. The effects of intraoperative changes in plasma colloid osmotic pressure (COP) on the formation of intestinal edema were studied in patients during modified Whipple's operation (hemipancreato-duodenectomy). Eighteen patients (ASA physical status I or II) were randomly assigned to one of three groups. They received either lactated Ringer's (RL group, n = 6), 10% hydroxyethyl starch (HES group, n = 6), or 20% human albumin (HA group, n = 6) as a volume replacement solution, which was given to maintain central venous pressure (CVP) at the preoperative level. Jejunal specimens were obtained after the first transsection of the jejunum and prior to the jejuno-jejunostomy. Their water fraction (g H2O/g tissue dry weight) was measured gravimetrically. COP was determined prior to induction of anesthesia and upon removal of the second jejunal sample. In the RL group, 3,850 +/- 584 ml (data are means +/- SEM) of volume replacement solution were infused from induction of anesthesia to removal of the second jejunal sample. In the HES group, 1,358 +/- 45 ml were infused, and in the HA group, 463 +/- 49 ml were infused. During this time, COP decreased from 20.3 +/- 0.5 mmHg to 14.1 +/- 0.6 mmHg in the RL group, remained at 22.0 +/- 0.9 mmHg in the HES group, and increased from 20.7 +/- 0.9 mmHg to 28.1 +/- 0.9 mmHg in the HA group.(ABSTRACT TRUNCATED AT 250 WORDS) To assess the safety and effectiveness of a sprayable, site-specific adhesion barrier system (SprayGel; Confluent Surgical, Waltham, MA) for reduction of adhesion formation.
                Prospective, randomized, controlled phase III trial.
                University clinic (Kiel, Germany) and private clinic (Bordeaux, France).
                Sixty-six women aged 34.9 years (range, 23-52 years) undergoing laparoscopic or open uterine myomectomy, enrolled over a 15-month period.
                Patients were randomized to receive either optimal surgical treatment plus adhesion barrier or optimal surgical treatment alone, followed by second-look laparoscopy.
                Initial and second-look laparoscopy procedures were assessed for incidence, extent, and severity of adhesions; all patients were followed for safety analysis.
                When compared with initial surgery, the mean adhesion tenacity score of adhesions seen at second-look laparoscopy was significantly reduced in treatment patients compared with control patients (0.6 vs. 1.7, a 64.7% reduction). Mean adhesion extent score at second-look laparoscopy compared with initial surgery was 4.5 cm(2) vs. 7.2 cm(2), mean adhesion incidence score was 0.64 vs. 1.22. Of 64 patients, 40 (62.5%) returned for second-look laparoscopy.
                This adhesion barrier was safe, well tolerated, and demonstrated efficacy in a population of patients known to be at risk for adhesion formation. There were no adverse effects attributable to the product and no patients in whom it could not be applied.
Implications for practice
There is evidence that the use of HA/CMC membrane reduces incidence, extent and severity of adhesions which may, theoretically, have implications in re-operative abdominal surgery. There is no evidence that the incidence of intestinal obstruction or need for operative intervention is reduced. HA/CMC appears to be safe but there may be a risk of leak when wrapped around an anastomoses. HA/CMC may be considered for intra-abdominal, adhesion prophylaxis at a surgeon’s discretion and clinical context.
Implications for research
Further research is needed to explore the effectiveness of other agents in abdominal surgery in general. Synergism, using agents which target different aspects of adhesiogenesis, with exploration effectiveness in a wide range of emergency and elective surgery should be considered. Longer term outcomes of recurrent intestinal obstruction and chronic pain, identification of high risk groups of patients with evaluation of cost-effectiveness are required.