Definition, Origin, Significance in Surgical Practice, and Treatment Options
; ; ; ; ;
Background: Intra-abdominal adhesions arise after more than 50% of all abdominal operations and are an important source of postoperative complications. They attach normally separated organs to each other and can cause major problems for the affected patients by giving rise to small bowel obstruction, chronic pelvic pain, dyspareunia, infertility, and higher complication rates in subsequent operations. They are also a frequent source of medicolegal conflict. Thus, every physician should be familiar with their mechanism of origin, their consequences, and the methods by which they can be prevented.
Methods: A selective PubMed/Medline search from 1960 onward as well as articles to which these publications referred. The expert consensus position of the European Society for Gynaecological Surgery is also taken into consideration.
Results: Adhesions arise through aberrant wound healing after peritoneal injury with further influence from a variety of other factors. Preventive measures include minimizing peritoneal injury intraoperatively through the meticulous observance of basic surgical principles, moistening the mesothelium to keep it from drying out, irrigating the peritoneal cavity to remove blood and clot, and keeping the use of intra-abdominal foreign material to a minimum.
Conclusion: Adhesions are an inevitable consequence of intra-abdominal surgery. They can be prevented to some extent with meticulous surgical technique and certain other measures. For operations carrying a high risk of postoperative adhesions, e.g., surgery on the adnexa or
bowel, commercially available peritoneal instillates or barrier methods can be used to limit adhesion formation.
Intra-abdominal adhesions following surgery represent a major unsolved problem (1). They occur after 50% to 100% of all surgical interventions in the abdomen and can complicate future surgery considerably (2). Dembrowski published the first data on induction of adhesions in an animal model in 1889 (3), and the intervening 120 years have seen extensive studies in vitro and in vivo. Nevertheless, the literature contains neither an official definition of adhesions nor a recognized standardized classification for objective assessment of their extent and severity. Accordingly, study findings are often imprecise and do not lend themselves to adequate interpretation. By the same token, there is a lack of clinically oriented guidelines for the diagnosis, treatment and options for reduction of adhesions.
The severe consequences of intra-abdominal adhesions for patients, physicians, and healthcare systems stand in stark contrast to the low level of awareness and knowledge—due not least to the lack of standardization and the patchy data—among doctors. Against that backdrop, this article sets out to:
- Increase clinicians’ awareness of adhesions and their consequences
- Offer an overview of the pathogenesis of adhesions
- Describe universally applicable and readily implemented strategies to reduce the occurrence of adhesions
- Introduce commercial products for reduction of adhesions.
Material and methods
We performed the literature search for this review with the aid of our working group’s existing database. This database, comprising articles published in PubMed/Medline since 1960, is updated monthly by addition of all articles found using the search terms “adhesions”, “intraperitoneal adhesions”, “intraabdominal adhesions”, “adhesion reduction”, “adhesion prophylaxis”, and “adhesion formation”. It also contains relevant publications found in the reference lists of the articles identified. The expert consensus position of the European Society for Gynaecological Endoscopy was taken into consideration.
Types of adhesions
Intra-abdominal adhesions may be congenital or acquired. Congenital adhesions arise during physiological organogenesis—like the frequently observed attachment of the sigmoid colon to the left pelvic wall—or can be traced back to abnormal embryonal development of the abdominal cavity. They are usually asymptomatic and are diagnosed incidentally (4).
Postmortem examination of patients who had not undergone surgery identified postinflammatory adhesions in 28% of cases (5). These are caused by intra-abdominal inflammation or can be attributed to endometriosis, peritonitis, radiotherapy, or long-term peritoneal dialysis (4, 6, 7).
The greater omentum is involved in 80% of cases of postoperative intra-abdominal adhesions, the bowel in only around 50% (8). Ovarian adhesions can be demonstrated in over 90% of patients after gynecological adnexal surgery (9); this is explained by the high sensitivity of the ovarian epithelium and its proximity to other peritoneal surfaces (10). Patients at high risk of already having or developing adhesions are those with previous or planned adnexal interventions, ablation of endometriosis, or bowel surgery involving large peritoneal defects, together with all those who have undergone previous abdominal surgery with pronounced formation of adhesions.
Intra-abdominal adhesions are predominantly diagnosed intraoperatively. Careful history taking can substantiate the suspicion of adhesions; no other clinical investigations or imaging procedures enable a confident diagnosis. Evidence pointing to adhesions may be yielded by high-resolution ultrasonography and functional cine MRI, both of which detect limited movement relative to one another of organs joined by adhesions (e11, e12). However, neither of these modalities is established in routine clinical practice.
Complications of adhesions
The intra-abdominal adhesions that arise from the beginning of the surgical procedure can cause complications decades later (8, 11). The patients’ symptoms include meteorism, irregular bowel movements, chronic abdominal pain, digestive disorders, infantility, and intestinal obstruction, and often fail to be associated with their cause (12). In contrast to congenital or postinflammatory adhesions, which are mostly asymptomatic, postoperative adhesions cause 40% of all cases of intestinal obstruction. Stenoses of the large intestine are produced principally by malignancies and only rarely by adhesions, but adhesions cause 65% to 75% of small bowel obstruction—the most serious of all adhesion-induced complications (8). Particularly colectomy, involving a large peritoneal incision, carries an 11% cumulative risk of intestinal obstruction within the first year after operation (13).
Adhesions are responsible for 15% to 20% of all cases of secondary female infertility (14). Paraovarian, peritubal adhesions can lead to follicular entrapment and reduced mobility and mechanical blockade of the fallopian tubes. This may limit oocyte transport, increasing the risk of ectopic pregnancy (14, 15).
Chronic lower abdominal pain severely impairs the quality of life of those affected and forms the indication for 30% to 50% of all laparoscopies and 5% of hysterectomies (16). In his review of 11 studies, DiZerega showed that adhesions had been responsible for the chronic lower abdominal pain in only 40% of the women who had undergone surgery (17). In 25% of cases the cause remained unclear. Accordingly, it is difficult to advise those suffering from such pain whether an operation will reveal the cause and whether laparotomic or laparoscopic adhesiolysis may relieve their symptoms. In a prospective study, Keltz et al. observed a significant reduction in chronic abdominal pain after right-sided paracolic adhesiolysis (18). In contrast, Swank et al. found no amelioration of pain after laparoscopic release of adhesions not constricting the bowel (19).
Patients who have undergone surgery previously should be thoroughly informed about possible adhesiolysis and its potential complications and required to give their informed (or written) consent. Discussion points should include extension of the operation and anesthesia time, the increased blood loss and the significantly higher risk of injury to the omentum, bladder, ureters and vessels (20). Reoperations have a 20% rate of enterotomy—often associated with poorer patient outcome and longer hospital stay (20). Particularly in the case of known extensive intra-abdominal adhesions, the indication for any further operation should be considered very carefully because of the up to 85% likelihood of reformation or de novo formation of adhesions (21). If this occurs, future minimally invasive surgery may be difficult or even impossible (20, e2). Adhesion-related changes in pelvic anatomy can also complicate or prevent:
- Diagnostic ultrasonography
- Oocyte harvesting in the context of IVF treatment
- Performance of intraperitoneal chemotherapy or peritoneal dialysis (6, 7, e2).
Since intra-abdominal adhesions arise from aberrant peritoneal wound healing processes, any mesothelial damage by surgical trauma or bacterial inflammation can lead to their formation (22). Damage to the peritoneum is followed by capillary bleeding and increased vascular permeability with consequent exudation of fibrinogen (6, 22, e2). After cleavage of fibrinogen to fibrin and its bonding with fibronectin the defect is closed and a temporary wound bed forms (22, e13). Within the ensuing 72 h endogenous fibrinolytic activity of the mesothelial cells leads to breakdown of these fibrin deposits and thus to complete regeneration (e15).
A key role in the origin of adhesions is attributed to a pathological reduction in peritoneal fibrinolysis capacity (e16). This may result from destruction of mesothelia, from their insufficient supply with blood, from increased synthesis of fibrinolysis antagonists following trauma, from hypoxia, from radical formation, or from bacterial infection (22, e14, e16–e18). In the course of the subsequent organization processes the persisting fibrin matrix gives rise to a mesothelialized tissue structure that is stabilized by connective tissue and may contain arterioles, venules, capillaries, and nerve fibers (e14). An overview of the identified pathophysiological associations and the factors thought to be involved in the origin of adhesions is provided by the Figure (gif ppt), Table 1 (gif ppt) and the eBox (gif ppt).
Prevention of postoperative adhesions
Damage to the serosa and the use of intra-abdominal foreign bodies should be kept to a minimum (4). Blood and clot in association with a peritoneal wound constitute a potentiating factor, because additional fibrin has to be degraded by the fibrinolytic activity of the peritoneum (e24). Before closure of the abdominal wall, therefore, it is advisable to perform careful—though not excessive, to avoid necrosis—hemostasis and irrigate repeatedly with saline and Ringer solution. There is no consensus in the literature as to whether laparoscopy is associated with fewer de novo and recurring adhesions than laparotomy (8, e26). A lower rate of adhesion development in laparoscopic interventions could be related to reduction of peritoneal trauma as a result of more exact preparation under magnification (e3). Moreover, contamination of the abdominal cavity and adhesion-potentiating foreign-body reactions are reduced (e9). Further advantages include a minimized incidence of postoperative infections and a tamponade effect of the pneumoperitoneum in the event of hemorrhage. A disadvantage of laparoscopy, related to the longer operating time and the high insufflation pressure, is the risk of mesothelial injury; this can be reduced by using humidified and warmed gases (e25). With regard to development of adhesions, minimally invasive access via natural orifices (Natural Orifice Transluminal Endoscopic Surgery, NOTES) seems to be superior to both laparoscopy and laparotomy. In an animal study, Dubcenco found the lowest number and severity of adhesions in the group in which endoscopy was carried out by the orogastric route (e27).
In those at high risk the use of adhesion-reducing adjuvants can be considered independent of the extent and location of the mesothelial defect. The widely used, commercially available adjuvants licensed for use in Germany include:
- Humidified and warmed insufflation gases for laparoscopy
- Medicinal agents
- Colloid and crystalloid solutions
- Separators: fluids for peritoneal instillation or site-specific mechanical barriers.
Attempted drug treatment can involve local and systemic anti-inflammatory agents, fibrinolytics, or antibiotic solutions. Moreover, colloids (dextran) and crystalloid solutions (Ringer lactate or saline) have been used, alone or with corticosteroids or heparin, to separate peritoneal surfaces. No clinical study has yet demonstrated a clear adhesion-reducing benefit of these substances (25).
The 4% glucose polymer icodextrin is an adhesion-inhibiting peritoneal instillate. Besides its application for intraoperative moistening of peritoneal surfaces it is instilled into the abdominal cavity (e28). By virtue of its osmotic activity it is thought to retain fluid in the peritoneal cavity for 3 to 4 days and keep organs and injured peritoneal surfaces separated from each other until it is eliminated via the kidneys. Randomized, double-blind multicenter studies have confirmed the adhesion-reducing properties of icodextrin after surgery. Comparison of icodextrin and Ringer lactate revealed an advantage for the former with regard to the reduction of incidence (52% vs. 32%), extent (52% vs. 47%), and severity (65% vs. 37%) of adhesions. Clinical improvement was observed in 49% of patients following treatment with icodextrin, against 38% after Ringer lactate (e28–e30). Data from the European registry on the use of icodextrin (adeptTM Registry for Clinical Evaluation, ARIEL) demonstrate high user-friendliness and high patient safety. Complications described after icodextrin instillation are septic and inflammatory states, anastomotic insufficiency, and labial swelling (e31).
Cross-linked esters of hyaluronic acid form a viscous gel that is applied to traumatized peritoneal surfaces after abdominopelvic surgery to help keep them separate during the healing process. Few studies have been conducted on the efficacy of hyaluronic acid esters in preventing adhesions. In a group of 52 patients in a randomized multicenter study, application of hyaluronic acid gel was shown to reduce formation of adhesions after laparoscopic enucleation of myoma. Following treatment 62% of these patients were free of adhesions, compared to 41% of those who did not receive the gel. Application of the gel significantly lowered the difference in severity of intra-abdominal adhesions between first and subsequent operations (0.3 ± 0.9 vs. 0.8 ± 1.0, p<0.05) (e32). Furthermore, Pellicano et al. documented an increase in the rate of pregnancy from 38.8% to 77.8% in previously infertile women 12 months after laparoscopic enucleation of myoma with application of gel (e33).
Carboxymethylcellulose (CMC) and polyethylene oxide (PEO) form a gel-like resorbable barrier for sealing peritoneal surfaces and prevention of future adhesions. In a randomized study, 37 high-risk patients received a CMC/PEO barrier in the course of laparoscopic ablation of endometriosis. Follow-up laparoscopy documented a significant adhesion-reducing effect of this measure as assessed using the American Fertility Society score, with a decrease from 8.4±3 points to 6.2 ± 2 points. In the non-treated control group there was increased growth of adhesions and thus a rise in the score from 10 ± 2.5 points to 14 ± 3 points (e34).
A barrier membrane consisting of hyaluronic acid and CMC can separate peritoneal surfaces for around 7 days (10). Because of its high fragility this membrane is predominantly used in laparotomies (e35). The efficacy of such membranes in reducing intra-abdominal adhesions after enucleation of myoma and colectomy has been investigated in a number of randomized studies. With regard to the gynecological data, the Cochrane analysis by Ahmad et al. notes that the positive findings reported by Diamond et al. (e35) have to be interpreted with caution owing to statistical deficiencies (24). Follow-up laparoscopy 8 to 12 weeks after use of the barrier membrane on abdominal wall closure in patients undergoing colectomy and creation of an ileal pouch showed that 51% of treated patients were free of adhesions, against 6% in the control group (e36, e37). This barrier membrane is the only agent which has been specifically investigated for the reduction of the incidence of small bowel obstructions as a complication of adhesions: In a multicenter study conducted by Fazio et al. (e38), the membrane resulted in a 1.6% absolute and 47% relative reduction in the occurrence of this complication. It should be pointed out, however, that application of the membrane directly onto to the anastomosis sutures increased the risk of anastomotic insufficiency (e38).
Another type of adhesion barrier, applied as a spray, comprises a pair of polyethyleneglycols in a two-component system. The barrier is sprayed onto injured serosal surfaces and seals them for 7 to 14 days. Early clinical pilot studies showed an adhesion-preventing benefit of the spray, but this effect was not confirmed in subsequent, more extensive trials (e39, 23). Evaluation of the next-generation product in a porcine model showed a reduction in number (ca. 46%) and extent (ca. 83%) of the adhesions formed (e40).
Oxidized regenerated cellulose can be applied to injured surfaces as a resorbable membrane, following careful hemostasis. Moistening of the membrane stops it slipping and provides a physical barrier between tissues until the membrane is resorbed after 4 weeks. In their Cochrane analysis, Ahmad et al. conclude that oxidized regenerated cellulose leads to a reduction in the occurrence of pelvic adhesions after gynecological laparotomy and laparoscopy (24). It is advised, however, that this finding be interpreted with caution.
Since surgical treatment of adhesions is highly likely to be associated with the induction of new adhesions, reduction or prevention of adhesions should be every surgeon’s primary goal. In this regard, the Clinical Adhesion Research and Evaluation Group (CARE Group) has been founded at Giessen University Hospital. This interdisciplinary group aims to optimize patient care by integrating existing strategies into routine clinical practice and conducting research into new techniques for reducing adhesions. The general measures described in this review can readily be put into practice and comprise minimization of peritoneal injury by the following means: meticulous observance of established surgical principles, moistening of the mesothelium to keep it from drying out, reduction of the use of intra-abdominal foreign materials to a minimum, and irrigation of the abdominal cavity to remove blood and clot. Adhesion-reducing agents differ, sometimes considerably, in their indications and area of surgery. Their use is particularly advisable in high-risk patients.
Conclusive interpretation of the partially controversial study findings on adhesion-reducing adjuvants is hampered by the limited number of studies, the small numbers of patients, the large variety of factors influencing adhesion development, and the lack of a standardized classification of adhesions. The result is skepsis among clinicians and low acceptance of adhesion-reducing products. Moreover, it is often difficult to arrange for these products to be used because there is no provision for their reimbursement under the diagnosis-related groups system. Further high-quality studies are therefore required.
We thank Prof. Rudy Leon DeWilde of Pius Hospital Oldenburg, member of the Expert Adhesions Working Party of the European Society for Gynaecological Endoscopy (ESGE), for his help in writing and revising the manuscript.
Conflict of interest statement
Prof. Tinneberg has received reimbursement of travel costs and lecture fees from Baxter. Dr. Hackethal has received reimbursement of travel costs from Baxter und has consultancy contracts with NordicPharma und Fischer&Paykel. Dr. Tchartchian has a consultancy contract with and has received reimbursement of travel costs from Covidien.
Dr. Brüggmann, Dr. Wallwiener und Prof. Münstedt declare that no conflict of interest exists according to the guidelines of the International Committee of Medical Journal Editors.
Manuscript received on 10 August 2009, revised version accepted on 8 December 2009.
Translated from the original German by David Roseveare
Dr. med. Andreas Hackethal
Klinik für Gynäkologie und Geburtshilfe
35385 Gießen, Germany
@For eReferences please refer to:
eBox available at:
gynecologic surgery: clinical significance, etiology and prevention. Am J Obstet Gynecol 1994; 170: 1396–403. MEDLINE
J Surg Res 2009; 151: 40–7. MEDLINE
Klinik für Frauenheilkunde und Geburtshilfe des Pius Hospitals Oldenburg:
Dr. med. Tchartchian
Klinik für Gynäkologie und Geburtshilfe, Ruprecht-Karls-Universität Heidelberg:
Dr. med. Wallwiener
|1.||Diamond MP, El-Hammady E, Wang R, Kruger M, Saed G: Regulation of expression of tissue plasminogen activator and plasminogen activator inhibitor-1 by dichloroacetic acid in human fibroblasts from normal peritoneum and adhesions. Am J Obstet Gynecol. 2004; 190: 926–34. MEDLINE|
|2.||DiZerega GS: Contemporary adhesion prevention. Fertil Steril 1994; 61: 219–35. MEDLINE|
|3.||von Dembowski T: Über die Ursachen der peritonealen Adhäsionen nach chirurgischen Eingriffen mit Rücksicht auf die Frage des Ileus nach Laparotomien. Langenbecks Arch Chir 1889; 37: 745.|
|4.||Liakakos T, Thomakos N, Fine PM, Dervenis C, Young RL: Peritoneal adhesions: etiology, pathophysiology, and clinical significance. Dig Surg 2001; 18: 260–73. MEDLINE|
|5.||Weibel MA, Mayno G: Peritoneal adhesions and their relationship to abdominal surgery. A postmortem study. Am J Surg 1973; 126: 345–53. MEDLINE|
|6.||Cheong YC, Laird SM, Li TC, Shelton JB, Ledger WL, Cooke ID: Peritoneal healing and adhesion formation/reformation. Human Reprod Update 2001; 7: 556–66. MEDLINE|
|7.||Monk BJ, Berman ML, Montz FJ: Adhesions after extensive |
gynecologic surgery: clinical significance, etiology and prevention. Am J Obstet Gynecol 1994; 170: 1396–403. MEDLINE
|8.||Menzies D, Ellis H: Intestinal obstruction from adhesions: How big is the problem? Ann R Coll Surg Engl 1990; 72: 60–3. MEDLINE|
|9.||Pittaway DE, Daniell JF, Maxson WS: Ovarian surgery in an infertility patient as an indication for a short-interval second-look laparoscopy: a preliminary study. Fertil Steril 1985; 44: 611–4. MEDLINE|
|10.||Diamond MP, Pellicer A, Boyers SP, DeCherney AH: The effect of periovarian adhesions on follicular development in patients undergoing ovarian stimulation for in vitro fertilization-embryo transfer. Fertil Steril 1988; 49: 100–3. MEDLINE|
|11.||Ellis H, Moran BJ, Thompson JN, et al.: Adhesion-related readmissions after abdominal pelvic surgery: a retrospective cohort study. Lancet 1999; 353: 1476–80. MEDLINE|
|12.||Attard JA, MacLean AR: Adhesive small bowel obstruction: epidemiology, biology and prevention. Can J Surg. 2007; 50: 291–300. MEDLINE|
|13.||Nieuwenhuijzen M, Reijnen MM, Kuijpers JH, van Goor H: Small bowel obstruction after total or subtotal colectomy: a 10-year retrospective review. Br J Surg. 1998; 85: 1242–5. MEDLINE|
|14.||Stovall TG, Elder RF, Ling FW: Predictors of pelvic adhesions. J Reprod Med 1989; 34: 345–8. MEDLINE|
|15.||Molloy D, Martin M, Speirs A, et al.: Performance of patients with a „frozen pelvis“ in an in vitro fertilization program. Fertil Steril 1987; 47: 450–5. MEDLINE|
|16.||Howard FM: The role of laparoscopy as a diagnostic tool in chronic pelvic pain. Baillieres Best Pract Res Clin Obstet Gynaecol. 2000; 14: 467–94. MEDLINE|
|17.||DiZerega GS: Biochemical events in peritoneal tissue repair. Eur J Surg Suppl. 1997; 577: 10–6. MEDLINE|
|18.||Keltz MD; Gera PS; Olive DL: Prospective randomized trial of right-sided paracolic adhesiolysis for chronic pelvic pain. JSLS 2006; 10: 443–6. MEDLINE|
|19.||Swank DJ, Swank-Bordewijk SC, Hop WC, et al.: Laparoscopic adhesiolysis in patients with chronic abdominal pain: a blinded randomized controlled multi-center trial. Lancet 2003; 361: 1247–51. MEDLINE|
|20.||van der Krabben AA, Dijkstra FR, Nieuwenhuijzen M, et al.: Morbidity and mortality of inadvertent enterotomy during adhesiotomy. Br J Surg 2000; 87: 467–71. MEDLINE|
|21.||Diamond MP, Freeman ML: Clinical implications of postsurgical adhesions. Hum Reprod Update 2001; 7: 567–76. MEDLINE|
|22.||Reed KL, Fruin AB, Bishop-Bartolomei KK, et al.: Neurokinin-1 receptor and substance P messenger RNA levels increase during intraabdominal adhesion formation. J Surg Res 2002; 108: 165–72. MEDLINE|
|23.||DeWilde RL, Trew G, on behalf of the Expert Adhesions Working Party of the European Society of Gynaecological Endoscopy (ESGE): Postoperative abdominal adhesions and their prevention in gynaecological surgery. Expert consensus position. Part 2 – steps to reduce adhesions. Gynecol Surg 2007; 4: 243–53.|
|24.||Ahmad G, Duffy JM, Farquhar C, et al.: Barrier agents for adhesion prevention after gynaecological surgery. Cochrane Database Syst Rev 2008; (2): CD000475. MEDLINE|
|25.||Metwally M, Watson A, Lilford R, Vandekerckhove P: Fluid and pharmacological agents for adhesion prevention after gynaecological surgery. Cochrane Database Syst Rev 2006; 19: CD001298. MEDLINE|
|e1.||DeCherney AH, DiZerega GS: Clinical problem of intraperitoneal postsurgical adhesion formation following general surgery and the use of adhesion prevention barriers. Surg Clin North Am 1997; 77: 671–88. MEDLINE|
|e2.||Dijkstra FR, Nieuwenhuijzen M, Reijnen MMPJ, van Goor H: Recent clinical developments in pathophysiology, diagnosis and treatment of intra-abdomainal adhesions. Scand J Gastroenterol 2000; Suppl 232: 52–9. MEDLINE|
|e3.||Menzies D: Prospective adhesions: their treatment and relevance in clinical practice. Ann R Coll Surg Engl 1993; 75: 147–53. MEDLINE|
|e4.||Drollette CM, Badaway SZA: Pathophysiology of pelvic adhesions. J Reprod Med 1992; 37: 107–21. MEDLINE|
|e5.||Yesildaglar N, Koninckx PR: Adhesion formation in intubated rabbits increases with high insufflation pressure during endoscopic surgery. Hum Reprod 2000; 15: 687–91. MEDLINE|
|e6.||Molinas CR, Koninckx PR: Hypoxaemia induced by CO2 or helium pneumoperitoneum is a co-factor in adhesion formation in rabbits. Hum Reprod 2000; 15: 1758–63. MEDLINE|
|e7.||Ott DE: Laparoscopy and adhesion formation, adhesions and laparoscopy. Semin Reprod Med 2008; 26: 322–30. MEDLINE|
|e8.||Molinas CR, Mynbaev O, Pauwels A, Novak P, Koninckx PR: Peritoneal mesothelial hypoxia during pneumoperitoneum is a cofactor in adhesion formation in a laparoscopic mouse model. Fertil Steril 2001; 76: 560–7. MEDLINE|
|e9.||Torre M, Favre A, Pini Prato A, Brizzolara A, Martucciello G: Histologic study of peritoneal adhesions in children and rat model. Pediatr Surg Int 2002; 18: 673–6. MEDLINE|
|e10.||Luijendijk RW, de Lange DC, Wauters CC, et al.: Foreign material in postoperative adhesions. Ann Surg 1996; 223: 242–8. MEDLINE|
|e11.||Mussack T, Fischer T, Ladurner R, et al.: Cine MR imaging vs. high-resolution ultrasonography for detection of adhesions after laparoscopic and open incisional hernia repair. Surg Endosc 2005; 19: 1538–43. MEDLINE|
|e12.||Buhmann-Kirchhoff S, Lang R, Kirchhoff C, et al.: Functional cine MR imaging for the detection and mapping of intraabdominal adhesions: method and surgical correlation. Eur Radiol 2008; 18: 1215–23. MEDLINE|
|e13.||Reijnen MM, Bleichrodt RP, van Goor H: Pathophysiology of intra-abdominal adhesion and abscess formation, and the effect of hyaluronan. Br J Surg 2003; 90: 533–41. MEDLINE|
|e14.||diZerega GS, Campeau JD: Peritoneal repair and post-surgical adhesion formation. Hum Reprod Update 2001; 7: 547–55. MEDLINE|
|e15.||Sulaiman H, Dawson L, Laurent GJ, Bellingan GJ, Herrick SE: Role of plasminogen activators in peritoneal adhesion formation. Biochem Soc Trans 2002; 30: 126–31. MEDLINE|
|e16.||Holmdahl L, Erikkson E, Risberg B: Fibrinolysis in the human peritoneum during operation. Surgery 1996; 119: 701–5. MEDLINE|
|e17.||Halme J: Release of tumor necrosis factor-alpha by human peritoneal macrophages in vivo and in vitro. Am J Obstet Gynecol 1989; 161: 1718–25. MEDLINE|
|e18.||Fletcher NM, Jiang ZL, Diamond MP, Abu-Soud HM, Saed GM: Hypoxia-generated superoxide induces the development of the adhesion phenotype. Free Radic Biol Med 2008; 45: 530–6. MEDLINE|
|e19.||Raftery AT: Method of measuring fibrinolytic activity in a single layer of cells. J Clin Pathol 1981; 34: 625–9. MEDLINE|
|e20.||Reed KL, Heydrick SJ, Aarons CB, et al.: A neurokinin-1 receptor antagonist that reduces intra-abdominal adhesion formation decreases oxidative stress in the peritoneum. Am J Physiol Gastrointest Liver Physiol 2007: 293: G544–51. MEDLINE|
|e21.||van Hinsbergh VW, Kooistra T, Scheffer MA, Hajo van Bockel J, van Muijen GN: Characterization and fibrinolytic properties of human omental tissue mesothelial cells. Comparison with endothelial cells. Blood 1990; 75: 1490–7. MEDLINE|
|e22.||Whawell SA, Scott-Coombed DN, Vipond MN, et al.: Tumour necrosis factor mediated release of plasminogen activator inhibitor-1 by human peritoneal mesothelial cells. Br J Surg 1994; 81: 214–6. MEDLINE|
|e23.||Tietze L, Elbrecht A, Schauerte C, et al.: Modulation of pro- and antifibrinolytic properties of human peritoneal mesothelial cells by transforming growth factor-b1 (TGF-b1), tumor necrosis factor-a (TNF-a) and interleukin-1b (IL-1b). Thromb Haemost 1998; 79: 362–70. MEDLINE|
|e24.||Golan A, Winston RML: Blood and intraperitoneal adhesion formation in the rat. J Obstet Gynaecol 1989; 9: 248–52.|
|e25.||Peng Y, Zheng M, Ye Q, Chen X, Yu B, Liu B: Heated and humidified CO2 prevents hypothermia, peritoneal injury, and intra-abdominal adhesions during prolonged laparoscopic insufflations. |
J Surg Res 2009; 151: 40–7. MEDLINE
|e26.||Gutt CN; Oniu T; Schemmer P; Mehrabi A; Buchler MW: Fewer adhesions induced by laparoscopic surgery? Surg Endosc 2004; 18: 898–906. MEDLINE|
|e27.||Dubcenco E, Assumpcao L, Dray X, et al.: Adhesion formation after peritoneoscopy with liver biopsy in a survival porcine model: comparison of laparotomy, laparoscopy, and transgastric natural orifice transluminal endoscopic surgery (NOTES). Endoscopy. 2009; 41: 971–8. MEDLINE|
|e28.||diZerega GS, Verco SJS, Young P, et al.: A randomized, controlled pilot study of the safety and efficacy of 4% icodextrin solution in the reduction of adhesions following laparoscopic gynaecological surgery. Hum Reprod 2002; 17: 1031–8. MEDLINE|
|e29.||Brown CB, Luciano AA, Martin D, Peers E, Scrimgeour A, diZerega GS, on behalf of the Adept Adhesion Reduction Study Group: Adept (4% icodextrin solution) reduces adhesions after laparoscopic surgery for adhesiolysis: a doubleblind, randomized, controlled study. Fertil Steril 2007; 88: 1413–26. MEDLINE|
|e30.||Kossi J, Gronlund S, Uotila-Nieminen M, Crowe A, Knight A, Keranen U: The effect of 4% icodextrin solution on adhesiolysis surgery time at the Hartmann’s reversal: a pilot, multicentre, randomized control trial vs lactated Ringer’s solution. Colorectal Dis 2009; 11: 168–72. MEDLINE|
|e31.||Menzies D, Pascual MH, Walz MK, et al.: Use of Icodextrin 4% solution in the prevention of adhesion formation following general surgery: from the multicentre ARIEL Registry. Ann R Coll Surg Engl 2006; 88: 375–82. MEDLINE|
|e32.||Mais V, Bracco GL, Litta P, Gargiulo T, Melis GB: Reduction of postoperative adhesions with an auto-crosslinked hyaluronan gel in gynaecological laparoscopic surgery: a blinded, controlled, randomized, multicentre study. Hum Reprod. 2006; 21: 1248–54. MEDLINE|
|e33.||Pellicano M, Guida M, Bramante S, et al.: Reproductive outcome after autocross-linked hyaloronic acid gel application in infertile patients who underwent after laparoscopic myomectomy. Fertil Steril 2005; 83: 498–500. MEDLINE|
|e34.||DiZerega GS; Coad J; Donnez J: Clinical evaluation of endometriosis and differential response to surgical therapy with and without application of Oxiplex/AP* adhesion barrier gel. Fertil Steril 2007; 87: 485–9. MEDLINE|
|e35.||Diamond MP: The Seprafilm Adhesion Study Group. Reduction of adhesions after uterine myomectomy by Seprafilm membrane (HAL-F): a blinded, prospective, randomized, multicenter clinical study. Fertil Steril 1996; 66: 904–10. MEDLINE|
|e36.||Becker JM, Dayton MT, Fazio VW, et al.: Prevention of postoperative abdominal adhesions by a sodium hyaluronate-based bioresorbable membrane: a prospective, randomized, double-blind multicenter study. J Am Coll Surg 1996; 183: 297–306. MEDLINE|
|e37.||Vrijland WW, Tseng LN, Eijkman HJ, et al.: Fewer intraperitoneal adhesions with use of hyaluronic acid-carboxymethylcellulose membrane: a randomized clinical trial. Ann Surg 2002; 235: 193–9. MEDLINE|
|e38.||Fazio VW, Cohen Z, Fleshman JW, et al.: Reduction in adhesive small-bowel obstruction by Seprafilm adhesion barrier after intestinal resection. Dis Colon Rectum 2006; 49: 1–11. MEDLINE|
|e39.||Mettler L, Audebert A, Lehmann-Willenbrock E, Schieve K, Jacobs VR: Prospective clinical trial of SpayGel as a barrier to adhesion formation: an interim analysis. J Am Assoc Gynecol Laparosc 2003; 10: 339–44. MEDLINE|
|e40.||Ferland R, Campbell PK: Pre-clinical evaluation of a next-generation spray adhesion barrier for multiple site adhesion protection. Surg Technol Int. 2009; 18: 137–43. MEDLINE|
Application of bioderadable materials based on alginate and pectin to prevent the formation of peritoneal adhesionsProceedings of the National Academy of Sciences of Belarus, Medical series, 201910.29235/1814-6023-2019-16-1-46-55
Deutsches Aerzteblatt Online, 201110.3238/arztebl.2011.0205a
Carboxymethyl Cellulose, Pluronic, and Pullulan-Based Compositions Efficiently Enhance Antiadhesion and Tissue Regeneration Properties without Using Any Drug MoleculesACS Applied Materials & Interfaces, 202110.1021/acsami.0c21938
Khirurgiya. Zhurnal im. N.I. Pirogova, 202010.17116/hirurgia202003129
3D Printing of Poloxamer 407 Nanogel Discs and Their Applications in Adjuvant Ovarian Cancer TherapyMolecular Pharmaceutics, 201910.1021/acs.molpharmaceut.8b00836
Oxidative Medicine and Cellular Longevity, 201910.1155/2019/4591384
Perm Medical Journal, 201910.17816/pmj36372-90
World Journal of Gastrointestinal Surgery, 201910.4240/wjgs.v11.i2.85
Postoperative peritoneal adhesion: an update on physiopathology and novel traditional herbal and modern medical therapeuticsNaunyn-Schmiedeberg's Archives of Pharmacology, 202110.1007/s00210-020-01961-8
Journal of Surgery and Medicine, 202010.28982/josam.714575
Inherited genetic predispositions in F13A1 and F13B genes predict abdominal adhesion formation: identification of gender prognostic indicatorsScientific Reports, 201810.1038/s41598-018-35185-x
Influence of postoperative adhesions after caesarean section on chronic lower back pain – A pilot study of osteopathic manipulative treatment.European Journal of Osteopathic Research, 201910.35740/EJOR.2019.1.1.5
Journal of Anatomy and Histopathology, 202010.18499/2225-7357-2020-9-2-90-99
Bowel adhesion and therapy with the stable gastric pentadecapeptide BPC 157, L-NAME and L-arginine in ratsWorld Journal of Gastrointestinal Pharmacology and Therapeutics, 202010.4292/wjgpt.v11.i5.93
Deutsches Aerzteblatt Online, 201110.3238/arztebl.2011.0205b
ACS Applied Materials & Interfaces, 202010.1021/acsami.0c00497
Acta Biomedica Scientifica (East Siberian Biomedical Journal), 201910.29413/ABS.2018-3.6.15
Emergency Medicine International, 201910.1155/2019/3647356
Decreasing recurrent bowel obstructions, improving quality of life with physiotherapy: Controlled studyWorld Journal of Gastroenterology, 201810.3748/wjg.v24.i19.2108