OBJECTIVE: To test the hypothesis that intraperitoneal instillation of a single bolus dose of l-alanyl-l-glutamine (AG) will reduce the incidence, extent and/or severity of adhesions following myomectomy and establish preliminary safety and tolerability of AG in humans.
METHODS: Phase 1,2 Randomized, double-blind, placebo-controlled study (DBRCT).
METHODS: Tertiary care gynecology surgical centre.
METHODS: Thirty-eight women who underwent myomectomies by laparoscopy (N = 38; AG-19 vs Placebo-19) or laparotomy (N = 10; AG-5 vs Placebo-5) with a scheduled second-look laparoscopy (SLL) 6-8 weeks later. Thirty-two patients in the laparoscopy arm completed SLL.
METHODS: Bolus dose of AG or normal saline solution control (0.9% NaCl) administered intraperitoneally immediately prior to suture closure of the laparoscopic ports. The average dose was 170 mL of AG or control based on a dosing scheme of 1 g/kg bodyweight.
METHODS: Digital recordings obtained for all procedures. The primary endpoint was reduction in the incidence, severity and extent of post-operative adhesions analyzed by intention-to-treat (ITT) approach. Three independent, blinded reviewers evaluated all operative video recordings to assess presence of adhesions. Post-hoc analysis assessed presence or absence of adhesions in the peritoneal cavity. Secondary endpoints assessed safety and tolerability of AG.
RESULTS: Administration of AG reduced the incidence, severity and/or extent of post-operative adhesions (p = 0.046). The presence of adhesions in the AG group was lower than in the Control group (p = 0.041). Adhesion improvement was achieved in 15 of 15 (100%) in the AG group versus 5 of 17 (29.6%) in the placebo group. No serious adverse events were reported. No differences in safety parameters were observed.
CONCLUSIONS: Intraperitoneal l-alanyl-l-glutamine reduced adhesion formation in all patients following laparoscopic myomectomy. Complete absence of adhesions was achieved at all abdominal sites in 93% of patients. Results confirm AG\'s known effects on cellular mechanisms of adhesiogenesis and lay the foundation for new adhesion prophylaxis research and treatment.

Adhesions are a common consequence of abdomino-pelvic surgery. Efficacy of available adhesion prevention agents is discussed controversially. Here, we used the adhesion barrier 4DryField PH: a powder, which is transformed into a barrier gel with saline solution. The study includes 40 consecutive patients with surgeries for adhesiolysis, endometriosis and other gynaecological pathologies and subsequent second look interventions. The intervention group (n = 17) received 4DryField PH gel while control patients (n = 23) did not receive any adhesion prevention. Severity and extent of adhesion formation were scored during both interventions using an established score. Direct comparison between first and second interventions showed that extent and severity of adhesions could be reduced significantly using 4DryField PH gel. In contrast, in the control group, extent was not reduced and severity was even significantly higher. Direct comparison of second look laparoscopies revealed that adhesion extent and severity were significantly lower in the 4DryField PH than in the control group.Impact StatementWhat is already known on this subject? Adhesion formation after gynaecologic surgeries is known to be frequent and highly problematic as it directly induces complications and additionally makes subsequent surgeries more difficult. The effectiveness of established adhesion barriers is not sufficient to tackle these problems adequately.What the results of this study add? This is the first controlled study using the relatively new adhesion barrier 4DryField PH. It yields a significant reduction of extent as well as severity of adhesions, while adhesiolysis surgery alone does not solve the problem.What the implications are of these findings for clinical practice and/or further research? Usage of 4DryField PH gel seems to be a good approach to solve the adhesion problem of gynaecologic surgery in general and the reformation problem of adhesiolysis surgery specifically. The results should be confirmed in a larger prospective randomised controlled trial.

OBJECTIVE: The aim is to evaluate the efficacy of poloxamer/alginate/CaCl2 mixture (PACM) solution/gel and hyaluronic acid/carboxymethylcellulose (HA-CMC) solution for reducing pelvic adhesion in a rat uterine horn model.
METHODS: A total of 48 females, Sprague Dawley rats, were divided into three groups according to the applied materials. A uterine horn adhesion model was created. The control group (group CO; n = 16) received no special materials except saline infusion. The experimental groups were treated with 1.0 mL HA-CMC solution (group HA-CMC; n = 16) or 1.0 mL PACM solution/gel (group PACM; n = 16). Adhesion scores were evaluated with macroscopic, microscopic, and immunohistochemistry grading 14 days postoperatively.
RESULTS: Macroscopic adhesion scores, including extent, severity, and total scores in group HA-CMC and group PACM, were significantly lower than those in group CO (P < .001). Among these three categories of scoring, group PACM had a significantly lower score than did group HA-CMC in adhesion severity (P = .025). In the microscopic adhesion score analysis, the fibrosis scores in group HA-CMC and group PACM were also significantly lower than that of group CO. In group PACM, the fibrosis score was significantly lower than that of group HA-CMC. There were no statistical differences across all three groups in the microscopic inflammation and immunohistochemistry staining.
CONCLUSIONS: Both HA-CMC solution and PACM solution/gel effectively reduced adhesion formation. PACM solution/gel was superior to HA-CMC solution in preventing pelvic adhesion, especially in adhesion severity and microscopic fibrosis.

BACKGROUND: Perihepatic adhesions induced by hepatectomy make the subsequent repeat hepatectomy technically demanding. The aim of this study was to verify the effect of hyaluronic acid/carboxymethyl cellulose-based bioresorbable membrane (HA membrane) in preventing posthepatectomy adhesion formation by focusing on the ease of the adhesiolysis in subsequent hepatectomy for recurrent tumors.
METHODS: A total of 201 patients who underwent hepatectomy using HA membrane were prospectively followed-up for 3 years. Thirty of the 201 patients underwent a repeat hepatectomy for recurrence. The operative data of 85 cases of repeat hepatectomy, the primary hepatectomy of which had been performed without the use of HA membrane, served as the historical control data. The primary endpoint was the time interval between the skin incision and the start of hepatic parenchymal transection (the preparation time) including adhesiolysis. Secondary endpoints were blood loss during the operation, incidence of postoperative complications, and the biochemical data.
RESULTS: The median preparation time (183 vs. 228 min; p = 0.027) and total operation time (374 vs. 439 min; p = 0.041) were significantly shorter in the HA membrane group than in the control group.
CONCLUSIONS: Use of HA membranes during hepatectomy enabled significant shortening of the adhesiolysis time during the sequential hepatectomy performed for recurrent tumors.

Periadnexal adhesions are known to contribute to subfertility. The restoration of the tubo-ovarian anatomy is one the key principles in reproductive surgery, and this involves adhesiolysis. However, adhesion formation/reformation is very common after periovarian adhesiolysis. It is not known if the application of Hyalobarrier®, an anti-adhesion gel, around the adnexal region postsurgery influences ovulatory status. The study is a pilot randomized controlled trial (RCT) randomizing women into the application of Hyalobarrier® versus no Hyalobarrier® at the time of laparoscopy, where postsurgical ovulatory status and pregnancy rates were evaluated.
This was a pilot RCT where women were recruited from the gynecological and subfertility clinic who were deemed to require an operative laparoscopy. If intraoperatively they were found to have periovarian adhesions, they were randomized into having adhesiolysis with and without usage of Hyalobarrier®. Demographic details and intraoperative details including the severity, extent, and the ease of use of Hyalobarrier® were recorded. Prior to the surgery and postoperatively, the participants had their serum hormonal status (day 2 FSH, LH and day 21 progesterone) evaluated. Postoperatively, they underwent a follicular tracking cycle at 3 months.
Fifteen women were randomized into use of Hyalobarrier® (study group) and 15 into the no Hyalobarrier® group (control group) between December 2011 and January 2014. There was no difference in the patient characteristics in terms of age, BMI, the number of previous pregnancies, or the extent, site, and severity of adhesions between the two groups. There was no significant difference between the study versus control groups in terms of the hormonal profile (day 2 FSH and day 21 progesterone) before or after surgery. The 3-month postoperative day 10-12 follicular tracking findings and endometrial thickness were similar between the study and control groups. Four women were pregnant in the study group (24%) and one in the control group (7%) cumulatively over 2 years.
The use of Hyalobarrier® post salpingo-ovariolysis did not influence follicular development as inferred from the results of the day 21 progesterone and folliculogram on day 10-12 3-month postsurgery.
ISRCTN number, ISRCTN1833588.
Nordic Pharma.

OBJECTIVE: To evaluate the safety and efficacy of a new crosslinked hyaluronan (NCH) gel in reducing postoperative adhesions.
METHODS: Randomized controlled trial (Canadian Task Force classification I).
METHODS: Seven departments of obstetrics and gynecology in China.
METHODS: A total of 216 women scheduled for gynecologic laparoscopic surgery for primary removal of adhesions, myomas, ovarian cysts, or endometriotic cysts.
METHODS: Patients were randomized to receive either NCH gel or saline with 1:1 allocation.
RESULTS: All patients were evaluated using a modified American Fertility Society (mAFS) scoring system for the incidence, extent, and severity of pre-existing and postoperative adhesions at the 10 anatomic sites of ovaries/tubes and at the expanded 23 or 24 anatomic sites throughout the abdominopelvic cavity by laparoscopy. A total of 215 randomized patients were treated with either saline solution (108 of 108) or NCH gel (107 of 108), composing the full analysis set (FAS), and 196 patients (94 of 108 in the saline control group and 102 of 108 in the NCH gel group) completed the entire study, composing the per protocol set (PPS). The postoperative incidence of moderate or severe adhesions evaluated at the 10 sites (the primary endpoint for efficacy) was 27.7% in the control group and 9.8% in the NCH gel group, a difference of 14.4% (95% confidence interval [CI], 2.6%-20.6%) in the PPS, and 37.0% in the control group and 14.0% in the NCH gel group, a difference of 20.0% (95% CI, 8.9%-26.8%) in the FAS. The postoperative incidence of moderate or severe adhesions evaluated at the 24 sites was also significantly lower in the NCH gel group compared with the control group (5.9% vs 14.9%; p = .036) in the PPS. Also in the PPS, the NCH gel group had significantly lower postoperative adhesion scores of severity, extent, and mAFS: 60.0%, 50.8%, and 76.9%, respectively (median scores of the 10 sites; p = .002) and 48.5%, 50.0%, and 72.2% (median scores of the 24 sites; p = .001) lower than those recorded in the control group. No serious adverse events were observed, and the safety profile of NCH gel was comparable to that of saline control.
CONCLUSIONS: This study demonstrates that NCH gel is safe and significantly reduces adnexal adhesion formation and global adhesion formation throughout the abdominopelvic cavity after gynecologic laparoscopic surgery.

BACKGROUND: Peritoneal adhesions, the fibrotic bands that form between the surfaces in the peritoneal cavity following surgery, still pose a difficult clinical challenge.
OBJECTIVE: To evaluate the SprayShield™ Adhesion Barrier System (PEG ester amine solution and a buffer solution) in reducing post-operative adhesion formation.
METHODS: This was a prospective, multi-center, randomized, single blind study. A total of 11 subjects diagnosed with ulcerative colitis (UC) or familial adenomatous polyposis (FAP) were randomized: 8 to the SprayShield™ arm and 3 to the control arm. SprayShield™ was applied on the viscera directly under the midline peritoneal incision and at the site of ileostomy. During the follow-up surgery, the incidence, extent, and severity of post-operative adhesion formation were evaluated, as well as the time required to mobilize the ileal loop.
RESULTS: In patients who received SprayShield™ the time required to mobilize the ileal loop at the ileostomy closure was slightly shorter and the incidence and severity of adhesions were somewhat lower vs. control subjects (NS).
CONCLUSIONS: SprayShield™ was found to be easy to use, safe, and quick to apply, and performed well in adherence and conformity. The incidence and severity of adhesions were lower for SprayShield™ subjects vs. control subjects, but due to the limited number of patients there are not enough data to confirm the effectiveness of the SprayShield™ Adhesion Barrier System in prevention of adhesions.

OBJECTIVE: Postoperative adhesion is the most frequent complication of abdominal surgery. Therefore, we investigated the individual effects of synthetic barrier [hyaluronic acid/carboxymethylcellulose (HA/CMC)] and pharmacologic agents [low molecular weight heparin (LMWH) cyclo-oxygenase-2 inhibitor (COX-2 inhibitor)] using animal model of intra-abdominal adhesion.
METHODS: The cecum was rubbed with sterile alcohol wet gauze until subserosal haemorrhage and punctate bleeding developed under the general anesthesia. Five animal groups were prepared using the film HA/CMC, gel HA/CMC, LMWH and COX-2 inhibitor.
RESULTS: The grade of adhesion by modified Leach method for group I (control), II (film type HA/CMC), III (gel type HA/CMC), IV (LMWH) and V (COX-2 inhibitor) were 5.35±1.8, 6.15±1.3, 4.23±2.6, 5.05±0.7 and 5.50±0.9, respectively. Group III showed the least grade of adhesion and it is statistically significant in adhesion formation (p=0.028). The numbers of lymphocytes were significantly low in group III and group V compared to the control group (lymphocyte: p=0.004). The mast cell counts were generally low except for the control group (I: 1.05, II: 0.35, III: 0.38, IV: 0.20, V: 0.37), however, it was not statistically significant (p=0.066).
CONCLUSIONS: The gel barriers were shown to be partly efficient in inhibiting the formation of postoperative adhesions and might provide an option for abdominal surgery to reduce postoperative adhesions. The LMWH and COX-2 inhibitor had been known for their inhibitor effect of fibrin formation and anti-angiogenic/ anti-fibroblastic activity, respectively. However, their preventive effects of adhesion and fibrosis were found to be obscure.