Arthrofibrosis is a complication of intra-articular knee surgery which is caused by intra-articular fibrosis. To date, several preventive therapies for arthrofibrosis have been reported. This systematic review aims to summarize current knowledge about pharmacological arthrofibrosis prevention.

A systematic literature search was conducted in Medline, Web of Science, and Cochrane library using the search term 'Arthrofibrosis AND prevention'. Subsequently, articles reporting the effects of a preventive pharmacological intervention against arthrofibrosis were included in this review.

16 studies investigated the pharmacological prevention of arthrofibrosis of which 13 were conducted in animal models. Several drugs improved the range of motion (ROM) in animal models. Bevacizumab (ROM +39.4 degrees), nonsteroidal anti-inflammatory drugs (ROM +18.0-31.2 degrees), and rosiglitazone (ROM +19.5 degrees) significantly increased the ROM. Artesunate, mitomycin c, bevacizumab, hyaloglide, and botulinum toxin A significantly reduced adhesion scores. None of the drugs tested in humans improved the functional outcomes after joint arthroplasty. Methodological differences limited the ability to compare outcomes and, due to poor reporting of methodology, many studies had an unclear risk of bias.

This review identified several drugs as potential candidates for arthrofibrosis prevention. These drugs modulate inflammation or alter the activity of fibroblasts. Most studies are conducted in experimental animal models and none of these results are currently translated into a clinical application. Moreover, the methodology and route of administration varied between studies. Nor were dose dependency studies conducted. Future studies should adopt a standardized approach to determine the effects of preventive pharmacological interventions on arthrofibrosis.

Small-bowel obstruction (SBO) after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is a common complication associated with re-admission that may alter patients' outcomes. Our aim was to characterize and investigate the impact of bowel obstruction on patients' prognosis.

This was a retrospective analysis of patients with SBO after CRS/HIPEC (n = 392). We analyzed patients' demographics, operative and perioperative details, SBO re-admission data, and long-term oncological outcomes.

Out of 366 patients, 73 (19.9%) were re-admitted with SBO. The cause was adhesive in 42 (57.5%) and malignant (MBO) in 31 (42.5%). The median time to obstruction was 7.7 months (range, 0.5-60.9). Surgical intervention was required in 21/73 (28.7%) patients. Obstruction eventually resolved (spontaneous or by surgical intervention) in 56/73 (76.7%) patients. Univariant analysis identified intraperitoneal chemotherapy agents: mitomycin C (MMC) (HR 3.2, p = 0.003), cisplatin (HR 0.3, p = 0.03), and doxorubicin (HR 0.25, p = 0.018) to be associated with obstruction-free survival (OFS). Postoperative complications such as surgical site infection (SSI), (HR 2.2, p = 0.001) and collection (HR 2.07, p = 0.015) were associated with worse OFS. Multivariate analysis maintained MMC (HR 2.9, p = 0.006), SSI (HR 1.19, p = 0.001), and intra-abdominal collection (HR 2.19, p = 0.009) as independently associated with OFS. While disease-free survival was similar between the groups, overall survival (OS) was better in the non-obstruction group compared with the obstruction group (p = 0.03).

SBO after CRS/HIPEC is common and complex in management. Although conservative management was successful in most patients, surgery was required more frequently in patients with MBO. Patients with SBO demonstrate decreased survival.

Postoperative adhesions are most common issues for almost any types of abdominal and pelvic surgery, leading to adverse consequences. Pharmacological treatments and physical barrier devices are two main approaches to address postoperative adhesions but can only alleviate or reduce adhesions to some extent. There is an urgent need for a reliable approach to completely prevent postoperative adhesions and to significantly improve the clinical outcomes, which, however, is unmet with current technologies. Here we report that by applying a viscous, cream-like yet injectable zwitterionic polymer solution to the traumatized surface, postoperative adhesion was completely and reliably prevented in three clinically relevant but increasingly challenging models in rats. The success rate of full prevention is over 93% among 42 animals tested, which is a major leap in antiadhesion performance. Clinically used Interceed film can hardly prevent the adhesion in any of these models. Unlike current antiadhesion materials serving solely as physical barriers, the "nonfouling" zwitterionic polymer functioned as a protective layer for antiadhesion applications with the inherent benefit of resisting protein/cell adhesions. The nonfouling nature of the polymer prevented the absorption of fibronectins and fibroblasts, which contribute to the initial and late-stage development of the adhesion, respectively. This is the key working mechanism that differentiated our "complete prevention" approach from current underperforming antiadhesion materials. This work implies a safe, effective, and convenient way to fully prevent postoperative adhesions suffered by current surgical patients.

Postoperative adhesions are very common complications after general abdominal surgery. Although adhesiolysis has been proven effective in eliminating the preexisting adhesions, the new trauma caused by surgical lysis can induce recurrent adhesion. The prevention of recurrent adhesion after adhesiolysis is more difficult because the injury is more severe and adhesion mechanism is more complicated compared with the primary adhesion. In this study, a thermoresponsive hydrogel contained galactose modified xyloglucan (mXG) and hydroxybutyl chitosan (HBC) was developed as a barrier device for recurrent adhesion prevention after adhesiolysis due to its injectability and spontaneous gelling behaviors at the body temperature without any chemical reactions or extra driving factors. First, mXG and HBC were synthesized via enzymatic modification and etherification reaction, respectively. Rheological measurements indicated that the mXG/HBC composite system showed excellent thermosensitivity properties, and their gelation temperature and time can be modulated via adjusting the mXG/HBC ratio. Moreover, the mXG/HBC hydrogel exhibited excellent cytocompatibility and hemocompatibility in vitro. Furthermore, the mXG/HBC hydrogel could promote wound healing in the rat skin wound model. Finally, the efficacy of the mXG/HBC composite hydrogel in the prevention of recurrent adhesion was evaluated in a more rigorous rat repeated-injury adhesion model. The results demonstrated that the composite hydrogel could not only effectively prevent recurrent adhesion after adhesiolysis, but also promote wound healing and reduce scare formation. These results suggested that the mXG/HBC composite hydrogel may be a promising candidate as an injectable anti-adhesion system for clinical applications.

Although adhesiolysis has been proven effective in eliminating the preexisting adhesions, the new trauma caused by surgical lysis can induce recurrent adhesion. So far, most of the existing barrier systems and pharmacological approaches were developed for primary adhesion prevention while few attention has paid on prevention of recurrent adhesion after adhesiolysis. In the present study, we developed a thermoresponsive polysaccharide-based composite hydrogel by simple mixing galactose modified xyloglucan (mXG) and hydroxybutyl chitosan (HBC). The resulting mXG/HBC composite hydrogel not only was easy to handle and highly effective in preventing the recurrent adhesion after adhesiolysis, but also could promote wound healing and reduce scare formation. Our study provide an effective anti-adhesion system for preventing recurrent adhesion after adhesiolysis.

Postoperative adhesions are pathological attachments that develop between abdominopelvic structures following surgery. Considered unavoidable and ubiquitous, postoperative adhesions lead to bowel obstructions, infertility, pain, and reoperations. As such, they represent a substantial health care challenge. Despite over a century of research, no preventive treatment exists. We hypothesized that postoperative adhesions develop from a lack of movement of the abdominopelvic organs in the immediate postoperative period while rendered immobile by surgery and opiates, and tested whether manual therapy would prevent their development. In a modified rat cecal abrasion model, rats were allocated to receive treatment with manual therapy or not, and their resulting adhesions were quantified. We also characterized macrophage phenotype. In separate experiments we tested the safety of the treatment on a strictureplasty model, and also the efficacy of the treatment following adhesiolysis. We show that the treatment led to reduced frequency and size of cohesive adhesions, but not other types of adhesions, such as those involving intraperitoneal fatty structures. This effect was associated with a delay in the appearance of trophic macrophages. The treatment did not inhibit healing or induce undesirable complications following strictureplasty. Our results support that that maintained movements of damaged structures in the immediate postoperative period has potential to act as an effective preventive for attenuating cohesive postoperative adhesion development. Our findings lay the groundwork for further research, including mechanical and pharmacologic approaches to maintain movements during healing.

Postoperative intra-abdominal adhesions represent a serious clinical problem. In this review, we have focused on recent progress in the cellular and humoral mechanisms underpinning adhesion formation, and have reviewed strategies that interfere with these pathways as a means to prevent their occurrence. Current and previous English-language literature on the pathogenesis of adhesion formation was identified. As the burden of surgical disease in the world population increases, and the frequency of reoperation increases, prevention of adhesion formation has become a pressing goal in surgical research.

We investigated the effect of mitomycin-C on the reduction of the formation of peritendinous fibrous adhesions after tendon repair. In 20 Wistar albino rats the tendo Achillis was cut and repaired using a modified Kessler technique. The rats were divided into two equal groups. In group 1, an injection of mitomycin-C was placed between the tendon and skin of the right leg. In group 2, an identical volume of sterile normal saline was injected on the left side in a similar fashion. All the rats received mitomycin-C or saline for four weeks starting from the day of operation. The animals were killed after 30 days. The formation of peritendinous fibrous tissue, the inflammatory reaction and tendon healing were evaluated. The tensile strength of the repaired tendons was measured biomechanically. Microscopic evidence of the formation of adhesions and inflammation was less in group 1. There was no significant difference in the tensile load required to rupture the repaired tendons in the two groups. Mitomycin-C may therefore provide a simple and inexpensive means of preventing of post-operative adhesions.

Choanal stenosis has recently been recognized as a late complication of radiation therapy for nasopharyngeal carcinoma. The management of velopharyngeal stenosis is challenging with high risk of restenosis. We report a case of velopharyngeal stenosis post-radiotherapy and illustrated the use of mitomycin-C to prevent restenosis. Mitomycin-C application has being shown useful adjunct to surgical technique in managing nasopharyngeal stenosis for surgeons.

Postoperative adhesion formation is a significant health-care problem with no universally accepted method of prevention. Barrier methods of prevention have been extensively tested and licensed, and this article examines the evidence.

Intraabdominal adhesion formation is a frequent problem after major abdominal surgery. For many years, there have been various attempts to decrease adhesions by using systemic and local drugs and mechanical barriers. In this study we aimed to evaluate the antifibrinolytic antiadhesive effects of mitomycin C (MMC) and streptopeptidase A (SA) against intraabdominal adhesions. Forty-eight rats were divided into six groups, each with eight rats. Group 1 (sham group) rats were laparotomized by transverse incision only. In Group 2 (laparotomy and talcum powder), 2 ml talcum powder was scattered equally onto the intestinal surface after laparotomy. Group 3 (SA only), 2 g SA was introduced onto the intestinal surface. Group 4 (talcum powder and SA), 2 ml talcum powder was scattered onto the intestinal surface and then 2 g SA was applied on the same area. Group 5 (MMC only), 2 ml MMC was introduced onto the intestinal surface. Group 6 (talcum powder and MMC), 2 ml talcum powder was scattered onto intestinal surface and then MMC was applied onto same area. We assessed adhesion grades macroscopically, as well as, hydroxproline levels biochemically. Macroscopicaly, the number of rats with moderate or severe adhesions was significantly higher in the control group than all other groups (P < 0.05). SA and MMC groups had only mild adhesions. No intraabdominal problem was detected in rats with SA or MMC. Hydroxyproline (HP) levels were significantly higher in control group than all other groups (P < 0.05). There was no statistical significance between the rats with SA and MMC (P > 0.05) according to the HP measurements. MMC and SA may have potential antiadhesive effects. Both substances could be beneficial against adhesion formation after laparotomies.

Damage to the peritoneum during abdominal surgery triggers a cascade of events aimed at repairing the damage. As part of this process, fibrin is deposited, which is the precursor to the formation of an adhesion between 2 damaged peritoneal surfaces. This can have a significant impact on morbidity and even mortality as well as large cost implications. Strategies to reduce adhesion formation include improving surgical techniques, optimizing laparoscopy conditions, using pharmacologic interventions targeted at the inflammatory response and/or fibrin deposition, and using agents that provide a physical barrier to adhesion formation. While these strategies have provided some success, none have yet proved totally successful in abolishing adhesions. Further research to ensure that adhesion prevention is optimal is therefore essential.

Infertility and intestinal obstruction are well-known complications, arising from adhesion formation after intra-abdominal operations. Basic principles of adhesion formation have been found through animal studies. In addition, examination of agents for the prevention of adhesions can be easily made using experimental studies. However, lack of uniformity in study design makes assessment of the efficacy of any prophylactic regimen difficult. In this review, the material and methods used in experimental studies designed for adhesion formation or prevention were evaluated in detail, with experimental studies published in the literature from 1960 to 2003 being evaluated. Several methods for adhesion induction have been described in the literature. Severity of the adhesion varies from method to method, with the main problem being the lack of uniform expression of study results. Extensive use of complex adhesion classification systems should be used to resolve this discordance between experimental studies.

To evaluate the efficacy of crosslinked hyaluronan (HA) hydrogels that contained covalently-bound mitomycin C (MMC) in reducing postoperative adhesions in a rat uterine horn model.

Two independent parameters were investigated: [1] the quantity of MMC in preformed crosslinked hydrogel films and [2] the efficacy of intraperitoneal injection of in situ crosslinkable solutions.

University animal research facility.

Female Wistar rats.

Injuries (3 x 10 mm) were made to contacting serosal surfaces of the medial uterine wall musculature in female rats. Two treatment protocols were used. In the first, sterile crosslinked HA films that contained different MMC loadings (0, 0.5%, and 2%) were applied to two injured uterine horns; control animals received no films. In the second protocol, MMC-loaded crosslinked HA gels that contained different MMC loadings (0.31%, 0.625%, and 1.25%) were spread on the site of uterine horn injury (1 mL); then, an additional 4 mL of the same formulation was injected into the peritoneal cavity after abdominal closure. Control animals were injected with 5 mL of buffer only.

Extent of postoperative adhesions between uterine horns and with surrounding tissues and organs.

Mitomycin C-loaded crosslinked HA films and in situ crosslinked gels were more effective in reducing postoperative adhesion formation than were buffer controls or crosslinked HA films without MMC.

Mitomycin C-loaded crosslinked HA films and gels reduced formation of postoperative intraperitoneal adhesions.

The role of topically applied mitomycin C in preventing postoperative perineural fibrosis was examined by gross anatomical dissection and histological analysis in rats. The sciatic nerve was exposed bilaterally in 24 Wistar adult male rats, and an abrasion injury was produced on the exposed surface of the biceps femoris muscle in all animals. In the experimental group, cotton pads soaked with mitomycin C (0.5 mg/ml) were placed around the nerves for 5 min, whereas cotton pads soaked with saline were applied to the control group. Four weeks after surgery, the neurolysis sites were evaluated by blinded surgical dissection. Perineural adhesions were graded using a numerical grading scheme. The scar tissue formation index was also calculated, and a grading was made according to the number of fibroblasts/fibrocytes counted around the epineurium in histological evaluation. Mitomycin C-treated nerves showed significantly less perineural adhesions than controls. Quantification of the dense connective tissue surrounding the nerves revealed a statistically significant reduction around nerves treated with mitomycin C, and the number of fibroblast/fibrocytes was also significantly reduced. Application of topical mitomycin C might be effective in preventing epineural scar formation after neurolysis of peripheral nerves.

A cross-linked hyaluronan (HA) hydrogel that contained a covalently bound derivative of the anti-proliferative drug mitomycin C (MMC) was synthesized and evaluated in vitro and in vivo. The HA-MMC hydrogel was prepared by coupling MMC-aziridinyl-N-acrylate with thiol-modified HA followed by cross-linking with poly(ethylene glycol) diacrylate (PEGDA). MMC was released from 0.5% and 2.0% MMC films by hydrolysis in proportion to the MMC loading. When incubated in vitro with human T31 tracheal scar fibroblasts, 0.5% MMC films inhibited proliferation, whereas 2.0% MMC films were cytotoxic. When implanted in vivo into a rat peritoneal cavity, neither 0.5% nor 2.0% HA-MMC films elicited a severe peritoneal fluid leukocyte response. Importantly, MMC reduced the thickness of fibrous tissue formed surrounding the implanted films. Thus, cross-linked HA-MMC films have strong potential as anti-fibrotic barriers for the prevention of post-surgical adhesions.

Adhesions between viscera and mesh may result in intestinal obstruction and fistulae formation. Fewer adhesions with sodium carboxymethylcellulose (SCMC)-coated polypropylene mesh (PM) has been reported, but impaired wound healing was the major concern. We investigated the adhesion-prevention effect of SCMC in different concentrations, as coating only on visceral face of PM and its effects on wound healing. A full-thickness abdominal wall defect was created in 28 rats, which were then divided into three groups. In Group I (control), the defect was repaired with PM only; in Group II and Group III, the defects were repaired with 1% and 1.6% SCMC-coated-PM, respectively. All animals were sacrificed at day 30, and histological evaluation and adhesion scoring were done. Animals in the group in which 1.6% SCMC-coated PM was used developed significantly fewer adhesions compared with other animals (P=0.04). Histological evaluation using a semiquantitative scoring system showed no difference between the groups in fibrosis and inflammation scores (P=0.9 and P=0.3, respectively), and thickness of fibrosis on mesh was also similar (P=0.5). SCMC in 1.6% concentration as coating only on the visceral face of PM reduced the incidence and severity of adhesions without impairing wound healing.