Peritoneal healing with adhesion formation: current comment

Intra-abdominal adhesions are fibrotic structures, which lie in the form of a string or attachment between the abdominal organs and connect these together. They are responsible for serious clinical complications that include intestinal obstruction, infertility, and pelvic pain. During the last century, surgeons' comprehensive understanding of the biology of peritoneal healing and wound repair has allowed them to identify a variety of new therapeutic techniques that limit the development of adhesion formation. New drugs, dextran 70 and poloxamer 407, have been developed to prevent adhesion formation. In addition, three new biomaterials (oxidized regenerated cellulose, hyaluronate membrane, and polytetrafluoroethylene) are synthetic barriers being used to prevent adhesions.     

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.     

The effectiveness of a single intraperitoneal infusion of a neurokinin-1 receptor antagonist in reducing postoperative adhesion formation is time dependent

BACKGROUND: Current methods to prevent intraabdominal adhesions are not uniformly effective. We recently showed in rats that a neurokinin-1 receptor (NK-1R) antagonist is capable of reducing adhesion formation. To determine the clinical feasibility of using an NK-1R antagonist to reduce adhesions, this study examined the time dependence for the effectiveness of NK-1R antagonist administration and its effects on wound healing. METHODS: Adhesions were surgically induced in rats receiving a single intraperitoneal infusion of the NK-1R antagonist, CJ-12,255, during or 1, 5, 12, or 24 hours after surgery. Adhesion formation was assessed 7 days later. In a subset of animals, tissue plasminogen activator (tPA) activity, which is a measure of peritoneal fibrinolytic activity, was determined in peritoneal fluid 24 hours after surgery (48 hours for animals infused at 24 hours). The tPA activity was also determined in nonoperated animals 24 hours after peritoneal injection of the NK-1R antagonist. Colonic burst pressures were measured 7 days after creation of anastomoses in rats that were administered the antagonist at surgery. RESULTS: The NK-1R antagonist significantly reduced (P=.003) intraabdominal adhesions when administered during or 1 hour after surgery, only moderately reduced (P=.08) adhesions when administered at 5 hours, and had no effect at 12 or 24 hours. Peritoneal tPA activity was significantly increased (P<.05) in peritoneal fluid 24 hours after administration of the NK-1R antagonist regardless of the surgical procedure. The NK-1R antagonist did not alter colonic anastomotic healing. CONCLUSIONS: These data show that some of the events critical to adhesion formation occur within the first 5 hours following an abdominal operation in this model. The fact that the NK-1R antagonist does not impair colonic anastomotic healing enhances its usefulness as a therapeutic agent to inhibit adhesion formation.     

Thermal preconditioning prevents peritendinous adhesions and inflammation

Adhesion formation is one of the foremost obstacles to a reliably good outcome in tendon and joint surgery. Thermal preconditioning has been found to reduce the inflammatory response through the induction of molecular chaperone expression, a recently described family of cytoprotective intracellular proteins. The authors analyzed the effect of thermal preconditioning on the inflammatory response to surgery, on tendon healing, and on the formation of peritendinous adhesions in 16 New Zealand White rabbits. Very significant decreases in adhesion formation and in the gliding and dimensions of tendons in animals that had thermal preconditioning were found. Tendons from these animals also showed a decreased level of adhesion formation and a significantly diminished inflammatory response on histologic examination with no biomechanically significant deleterious effect on the strength of tendon healing on testing load to failure. These findings are consistent with induction of heat shock proteins by hyperthermic pretreatment. Such prevention of peritendinous adhesions and the inflammatory response to injury and surgery without compromising healing are findings that have significant implications for tendon surgery and all surgery involving joints and soft tissues.     

免疫与炎症调节在腹腔粘连形成中的作用

腹腔粘连是临床常见的手术并发症,临床与实验研究证实：各种抗粘连药物和材料以及微创设备的应用并不能有效预防术后粘连的形成。为减少与控制粘连的发生,自世界第一台外科手术诞生以来,国内外学者从不同角度对腹腔粘连的发病机制进行研究,积累了大量文献。而免疫与炎症在腹腔粘连病理生理过程影响研究逐渐受到重视,笔者对国外学者进行的相关研究文献进行系统分析,旨在了解腹腔粘连炎症与免疫之间的关系,为临床防治提供新的靶标与路径。     

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.     

Adhesions from flexor tendon surgery: an animal study comparing surgical techniques

Intraoperative and postoperative hemorrhage has long been considered a cause of tendon adhesion and, thus, scarring and poor surgical results. To prevent such problems bipolar coagulators are commonly used during surgery to help achieve hemostasis. Surgical lasers also have been reported to help limit bleeding and scar formation. Very little is known regarding the relationship between hemorrhage and/or direct tendon tissue effects and tendon adhesions with the use of these modalities. We compared 3 different surgical techniques (meticulous sharp scalpel dissection, scalpel dissection plus bipolar coagulation, and CO(2) laser dissection) and used chicken flexor tendons to biomechanically and histologically assess the amount of adhesion formation after each procedure. Our findings show that bipolar coagulation and CO(2) laser application are both associated with significantly increased adhesion formation in tendon surgery compared with sharp dissection alone and that the meticulous, conventional sharp dissection technique is the best method to control adhesion formation. These conclusions have relevance to clinical tendon surgery.     

Peritoneal adhesions: etiology, pathophysiology, and clinical significance. Recent advances in prevention and management

AIM: To summarize the most common etiologic factors and describe the pathophysiology in the formation of peritoneal adhesions, to outline their clinical significance and consequences, and to evaluate the pharmacologic, mechanical, and surgical adjuvant strategies to minimize peritoneal adhesion formation. METHODS: We performed an extensive MEDLINE search of the internationally published English literature of all medical and epidemiological journal articles, textbooks, scientific reports, and scientific journals from 1940 to 1997. We also reviewed reference lists in all the articles retrieved in the search as well as those of major texts regarding intraperitoneal postsurgical adhesion formation. All sources identified were reviewed with particular attention to risk factors, pathophysiology, clinical manifestations, various methods, and innovative techniques for effectively and safely reducing the formation of postsurgical adhesions. RESULTS: The formation of postoperative peritoneal adhesions is an important complication following gynecological and general abdominal surgery, leading to clinical and significant economical consequences. Adhesion occur in more than 90% of the patients following major abdominal surgery and in 55-100% of the women undergoing pelvic surgery. Small-bowel obstruction, infertility, chronic abdominal and pelvic pain, and difficult reoperative surgery are the most common consequences of peritoneal adhesions. Despite elaborate efforts to develop effective strategies to reduce or prevent adhesions, their formation remains a frequent occurrence after abdominal surgery. CONCLUSIONS: Until additional information and findings from future clinical investigations exist, only a meticulous surgical technique can be advocated in order to reduce unnecessary morbidity and mortality rates from these untoward effects of surgery.     

Prevention of de novo adhesion by ferric hyaluronate gel after laparoscopic surgery in an animal model.

BACKGROUND AND OBJECTIVE: Adhesions remain a major cause of severe long-term complications. Attempts have been made to prevent adhesion formation by using endogenous or exogenous materials with controversial results. Our aim was to evaluate the efficacy of 0.5% ferric hyaluronate gel in the prevention of adhesion formation after laparoscopic surgery. METHODS: This was a prospective, randomized, experimental study (animal model). The study population comprised 75 female rabbits (Fauve de Bourgogne) weighing over 3 kg. The rabbits were randomized into 3 groups of 25 (hyaluronate, saline, and control) by using a predetermined computer-generated randomization code. All rabbits underwent a peritoneal laparoscopic resection, and the main outcome measure was the adhesion formation after laparoscopic surgery. RESULTS: The laparoscopic operating time and the mean interval before second-look surgery were not different among the 3 groups. The number of rabbits with adhesions did not differ among the 3 groups. The bowel adhesion rate was higher at the 10-mm trocar site than at the 5-mm trocar site (P=0.01). The adhesion scores did not differ among the 3 groups. A strong correlation was found between the values of the different adhesion scoring systems used. CONCLUSION: These results obtained in a rabbit model suggest that routine intraperitoneal application of hyaluronate gel does not prevent adhesion formation after laparoscopic surgery.     

Adhesion formation after flexor tendon repair: a histologic and biomechanical comparison of 2- and 4-strand repairs in a chicken model

PURPOSE: Both increased handling and increased bulk at the repair site have been hypothesized as affecting adhesion formation and gliding after tendon repair. Tendons repaired with 2- and 4-strand techniques were compared using both biomechanical and histopathologic measurements to determine the influence of increasing strand number on adhesion formation and gliding. METHODS: The flexor digitorum profundus tendon of the right middle toe of 80 broiler chickens was cut and then repaired with either a single (2-strand) or double (4-strand) modified Kessler core suture, followed by a running epitendinous suture. The limb was immobilized after surgery. Birds were killed at either 3 days or 4 weeks after tendon repair and adhesion formation measured using either biomechanical testing or quantitative and qualitative histology. For biomechanical testing, the tendon was pulled free of the sheath and a force versus displacement curve was generated. Comparisons of peak force and work to peak were made. Histologic specimens were examined by a pathologist blinded to the treatment group who scored the length and density of adhesions and made qualitative observations. RESULTS: Both biomechanical and histologic data showed expected differences in adhesion formation for early (3 days) and late (4 weeks) healing but no significant differences between 2- and 4-strand repairs. Biomechanical testing of 4-week specimens showed a nonsignificant tendency toward greater work required to break adhesions in 4-strand repairs. CONCLUSIONS: Adhesion formation and gliding resistance of tendons after 2- or 4-strand modified Kessler core suture were not significantly different, which suggests that simply increasing the number of strands crossing a repair does not necessarily result in more adhesions or resistance in this model.     

Intra-abdominal adhesions: cellular mechanisms and strategies for prevention

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.     

Evaluation of oxidized regenerated cellulose for prevention of postoperative intraperitoneal adhesions

Oxidized regenerated cellulose (ORC) is widely used to cover the denuded mesothelium and to promote hemostasis. We evaluated ORG in a rabbit model to assess the potential for adhesion reduction after uterine trauma and intestinal anastomosis. After surgery, a second laparotomy was done on postoperative day 7 for macroscopic evaluation of adhesion formation. The traumatized uterine horns wrapped in ORC had more numerous and higher grade adhesions compared with the non-surgical left, intact horns. However, when compared to the contralateral uterine horn which underwent trauma without ORG, a significant decrease in the grade of adhesion formation was noted. Rabbits undergoing intestinal anastomosis had the most pronounced degree of adhesion formation. Typically, the area of healing was encapsulated in a fibrin clot with adhesions attached to adjacent viscera. When ORC remained between the lesion and adjacent organs during mesothelial regeneration, adhesion formation decreased. However, the soft, gelatinous mass of ORC was also an effective nidus for clot formation. Where post-and intra-operative ooze produced a fibrin clot in the ORC, dense adhesions formed.     

Flexor tendon healing and adhesion formation after Sterispon wrapping: a study in the rabbit

The influence of Sterispon (Allen & Hanbury) wrapping on the healing of the rabbit flexor digitorum profundus tendon sutured within the digital sheath was studied. Control tendons healed in 2 weeks in association with thick adhesions. The wrapped tendons were surrounded with fewer adhesions, but 50 per cent separated. Healing was delayed until adhesions reached the suture site. A sheath of a single layer of mesothelial cells formed on the surface of the Sterispon opposite the tendon and this markedly reduced adhesions at the suture site. The cellular reaction was bland.Sterispon wrapping had a similar effect on tendon healing and adhesion formation as wrapping with other non-absorbable substances and the results support the theory that healing in the digital sheath is necessarily mediated through the formation of adhesions. Sterispon wrapping has been helpful after tenolysis operations.     

The SCAR-3 study: 5-year adhesion-related readmission risk following lower abdominal surgical procedures

OBJECTIVE: The Surgical and Clinical Adhesions Research (SCAR) and SCAR-2 studies demonstrated that the burden of adhesions following lower abdominal surgery is considerable and appears to remain unchanged despite advances in strategies to prevent adhesions. In this study, we assessed the adhesion-related readmission risk directly associated with common lower abdominal surgical procedures, taking into account the effect of previous surgery, demography and concomitant disease. METHODS: Data from the Scottish National Health Service medical record linkage database were used to assess the risk of an adhesion-related readmission following open lower abdominal surgery during April 1996-March 1997. RESULTS: Patients undergoing lower abdominal surgery (excluding appendicectomy) had a 5% risk of readmission directly related to adhesions in the 5 years following surgery. Appendicectomy was associated with a lower rate of readmission (0.9%), but contributed over 7% of the total lower abdominal surgery patient readmission burden. Panproctocolectomy (15.4%), total colectomy (8.8%) and ileostomy surgery (10.6%) were associated with the highest risk of an adhesion-related readmission. Overall, the risk of readmission was doubled in patients who had undergone abdominal or pelvic surgery within 5 years of the incident operation. A higher risk of readmission was also recorded in patients aged < 60 years compared with those aged > or = 60 yrs. The effect of gender was assessed. However, as the surgical codes used were found to be skewed towards women, these data have not been reported. Readmission risk was slightly higher in patients with concomitant peritonitis compared with patients without peritonitis. In contrast, Crohn's disease had no effect on risk. Patients with colorectal cancer had a lower risk of adhesion formation. However, this may have been due to the type of surgery performed in this patient group. CONCLUSION: The identification of high-risk patient subgroups may assist in effectively targeting adhesion-prevention strategies and the proffering of preoperative advice on adhesion risk.     

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.     

Postsurgical adhesion formation in germfree and ex-germfree rats--a study using three scoring scales.

Postsurgical adhesions occur commonly after surgical procedures and are the source of substantial postoperative morbidity. No preventive or prophylactic regimen against adhesions has proven successful in all circumstances. The reasons for this are not clear. The basic mechanisms causing adhesion formation have not been elucidated fully, and furthermore, lack of accurate methods of measuring adhesions may be a contributing factor. Postoperative adhesions may occur in all kinds of surgery but are especially prominent in the abdomen, where the bowel flora may be a compromising factor. This study was undertaken to study the influence of the gastrointestinal microflora on adhesion formation. Germfree and ex-germfree DA rats were subjected to a cecal crush model, and adhesions were evaluated after 7 days using 3 different scoring scales. Germfree rats formed significantly fewer adhesions than their ex-germfree (conventionalized) counterparts. The differences were so great that all three scoring scales achieved significance (p < .005). This study corroborates that the endogenous bowel flora per se is involved in adhesion formation without causing frank infection.     

Escin: Inhibiting Inflammation and Promoting Gastrointestinal Transit to Attenuate Formation of Postoperative Adhesions

Postoperative peritoneal adhesions are common, serious complications of general abdominal and gynecologic surgery that can lead to chronic abdominal pain, intestinal obstruction, and infertility. As yet, there are no ideal drugs that may be prescribed for patients to prevent adhesion formation effectively. In this study the effects of escin, a natural drug, on the various steps of adhesion formation were investigated. The effects of escin on increased vascular permeability induced by acetic acid in a mouse model of acute inflammation, granuloma formation in a subchronic inflammatory rat model, gastrointestinal transit in rats with intestinal paralysis, intestinal motility in postoperative patients, and postoperative adhesion formation in a rat model were observed. It was shown that escin could inhibit acute inflammation and granuloma formation, cause acceleration of gastrointestinal transit, help recover intestinal motility, and attenuate the formation of postoperative adhesions. The findings suggest that escin attenuates the formation of postoperative adhesions by inhibiting inflammation and promoting gastrointestinal transit. Thus it may be concluded that both inhibition of inflammation and increased gastrointestinal motility during the early postoperative period have a positive effect on decreasing the formation of adhesions.     

Association between the expression of mast cell chymase and intraperitoneal adhesion formation in mice

BACKGROUND: Adhesion formation is a major source of postoperative morbidity and mortality. Mast cells and their major protease, chymase, have been shown to participate in the healing process as well as in tissue remodeling. We aimed to identify the role of mast cells in intraperitoneal adhesion formation and to assess whether there is an association between the expression of mast cell chymase and adhesion formation. MATERIALS AND METHODS: Both mast cell-deficient W/W(V) mice and congenic +/+ mice received a standardized lesion produced by cecal scraping and the application of 95% ethanol. Adhesions were assessed blindly 1 week later using a standardized scale. In addition, histamine content, mast cell numbers, and chymase activity in cecum as well as at the healing sites were evaluated before and 7 days after surgical injury. RESULTS: A significant reduction in adhesion formation was seen in mast cell-deficient W/W(V) mice (P < 0.05). In the normal cecum, histamine content did not significantly differ between W/W(V) and +/+ mice. Chymase activity in cecum was detected in control +/+ mice, but not in W/W(V) mice. Mast cell numbers and chymase activity levels at the healing sites of +/+ mice were significantly increased 7 days after surgery. CONCLUSIONS: Our results indicate that mast cells contribute to intraperitoneal adhesion formation in mice, and suggest that chymase originating from mast cells is important in the development of adhesions.     

Prevention of adhesion to prosthetic mesh: comparison of different barriers using an incisional hernia model

OBJECTIVE: To assess whether use of antiadhesive liquids or coatings could prevent adhesion formation to prosthetic mesh. SUMMARY BACKGROUND DATA: Incisional hernia repair frequently involves the use of prosthetic mesh. However, concern exists about development of adhesions between viscera and the mesh, predisposing to intestinal obstruction or enterocutaneous fistulas. METHODS: In 91 rats, a defect in the muscular abdominal wall was created, and mesh was fixed intraperitoneally to cover the defect. Rats were divided in five groups: polypropylene mesh only (control group), addition of Sepracoat or Icodextrin solution to polypropylene mesh, Sepramesh (polypropylene mesh with Seprafilm coating), and Parietex composite mesh (polyester mesh with collagen coating). Seven and 30 days postoperatively, adhesions were assessed and wound healing was studied by microscopy. RESULTS: Intraperitoneal placement of polypropylene mesh was followed by bowel adhesions to the mesh in 50% of the cases. A mean of 74% of the mesh surface was covered by adhesions after 7 days, and 48% after 30 days. Administration of Sepracoat or Icodextrin solution had no influence on adhesion formation. Coated meshes (Sepramesh and Parietex composite mesh) had no bowel adhesions. Sepramesh was associated with a significant reduction of the mesh surface covered by adhesions after 7 and 30 days. Infection was more prevalent with Parietex composite mesh, with concurrent increased mesh surface covered by adhesions after 30 days (78%). CONCLUSIONS: Sepramesh significantly reduced mesh surface covered by adhesions and prevented bowel adhesion to the mesh. Parietex composite mesh prevented bowel adhesions as well but increased infection rates in the current model.