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Adhesions and their importance in Gynaecological Surgery

The percentage of incidence of adhesions after intra-abdominal surgery by laparotomy varies from 55 to 95 %. the average being 85 % (1-2).

 

Adhesion formation is still poorly understood but accounts for one third ( up to 35%) of the readmissions in classical surgery. The longer the postoperative period the more the readmissions are connected to adhesion formation (3). It was common belief that endoscopic surgery does reduce the number of postoperative adhesions and certainly the number of de novo adhesions. There is only clinical support for the de novo adhesions (4 -5).  Even the adhesion reformation after laparoscopic adhesiolysis does not differ from the adhesion formation at laparotomy (6). There is no difference at the site operated upon, on the opposite site there are slightly less adhesions as compared to open surgery. The symptoms depend on the location of the adhesions. Some adhesions are silent others give rise to pathological complications. Adhesions are the most common cause of small bowel obstruction (7-8). Secondary sub fertility is caused by adhesions in 20% of the cases (9 -10). Adhesions cause technical difficulties during subsequent operations and induce an increase in theatre time. This causes an increase in the health care costs (11). Peritoneal trauma is both necessary and sufficient for adhesion formation. The peritoneum reacts to trauma in a specific fashion regardless of how the cells are insulted. Once the trauma occurs there is a cascade of events that leads to normal regeneration of the single monolayer of peritoneal cells or adhesion formation.

 

 

Adhesions are formed because the fibrin deposits, forming on the location of a trauma because of the inflammation (set in motion by the endothelial lining damage and the release of cytokines, lymphokines, prostaglandins and blood), are not sufficiently absorbed.

 

 

 

 

 

 

 

There is evidence that the CO₂ gas, that we use to distend the abdomen, and even more so the pressure of the gas we use , to create the pneumoperitoneum, causes sufficient hypoxia to impair the proper protective function of the peritoneal endothelial lining.

 

 

It is poorly understood why some areas of the pelvis are more prone to adhesion formation. In the pelvic area 80% of the adhesions are formed over the fundus of the uterus, the tubes and the adnexal areas. If we consider strict mechanical criteria however these are the areas most exposed to the gas flow, as the gas is flowing in over the scope and hence in the direction of our vision. Vision correlated with the field we work in.

 

Adhesion formation starts within a very short interval after the initial trauma. In rats the time span is 24-36 hours after the peritoneal trauma (12). The first hours and days after a surgical intervention are critical. Within five weeks the adhesions are fully formed. Accumulated data strongly suggest that impaired fibrin clearance of the peritoneum favours adhesion formation (13). Trauma starts an inflammatory reaction; a sero- sanguinolent exudate is formed, rich in fibrin. Fibrin is part of the normal haemostasis process. It enhances the tissue repair by providing a matrix for the invading fibroblasts and the new blood vessels. However the resolution of these fibrin deposits is required to restore preoperative conditions. The dissolution is mediated by the fibrinolytic system. The inactive pro-enzyme plasminogen is converted into active plasmin by the t-Pa (tissue plasminogen activator). This active plasmin degrades the fibrin. If this fibrinolytic activity is insufficient fibrin deposits may persist causing the development of fibrinous adhesions. In these adhesions an organized fibroblast invasion takes place to form collagen. The concomitant vascular in growth then gives rise to permanent fibrous adhesions (14).

 

 

 

 

The main effort has to concentrate on adhesion prevention by maximal haemostasis and by maximal reduction of the surgical trauma and hence the inflammatory response and in doing so the formation of fibrin deposits. The best way to do so is using the microsurgical principles of gentle tissue handling, tissue hydratation and using non-absorbable sutures, the smallest possible. This limits the inflammatory response releasing less fibrin. The facilitation of the fibrin absorption should be enhanced. A maximal effort should be made to separate the traumatised tissues during the time the fibrin remains sticky.

Boys in 1942 described the treatment as “ five fundamental attacks directed towards the prevention of adhesions “ (15):

 

 

 

 

2.   Prevention of the coagulation of the serous exudates.

 

3.   Removal or dissolution of deposited fibrin.

 

4.   Prevention of the adherence of surfaces of adjacent structures by keeping them apart.

 

5.   Prevention of the organization of the persisting fibrin by means of inhibiting the fibroblastic proliferation.

 

 

Here we can be guided by the “Halstedian” principles, named after W.S.Halsted (1852-1925) (16). These principles boil down to what we know today as microsurgical principles:

 

·  Careful tissue handling

 

·  Forestall drying, suturing and clamping of tissues.

 

·  Leave behind as little foreign body material as possible.

 

·  Carry out a meticulous haemostasis under continuous irrigation

 

 

Microsurgery ads to these principles

 

·  The use of fine biocompatible suture material

 

·  The use of a-traumatic instruments.

 

·  The washing of the gloves to eliminate starch

 

·  The use of tissue friendly, moistened swabs.

 

·  The approximation of opposed tissues without strangling;

 

·  The use of irrigation to expose bleeders and to keep the peritoneum as moist as possible under the circumstances.

 

 

 (The single layer of mesothelial cells and their underlying extra cellular matrix are always moist in normal, non surgical, circumstances.)

 

 

The combination of these techniques united in the microsurgical approach reduces the incidence of adhesions when compared to the classical macro surgical technique. (17). It has become of general acceptance not to close the peritoneum after surgery. Peritoneum regenerates very rapidly without any adverse effects

 

(18). Of course when a technique has limited entry wounds, as operative laparoscopy has, the regeneration of the peritoneum is even more rapid. This could be the explanation why operative laparoscopy carries less risk for de novo adhesions.

 

(19). If we perform operations that carry a great risk for adhesion, de novo, formation we should plan an early second look laparoscopy to evaluate the extend of these adhesions and to perform adhesiolysis. The outcome of these second look laparoscopies is better the sooner these are performed after the initial operation. Trimbos-Kemper et al proved that half of the adhesions treated at early second look laparoscopy at the eight postoperative days did not recur after one year. (2)

 

Although in vitro heparinized solutions inhibit thrombosis and fibrin formation clinical results fail to demonstrate their efficacy. (20).

 

Recombinant tissue type plasminogen activator (rtPA), urokinase type plasminogen activator (uPA) and streptokinase appear to be capable to reduce and/or prevent peritoneal adhesions in animals in animal models and in humans by enhancing the endogenous fibrinolytic activity (21).

 

 

 

 

 

These stay longer in the abdomen than what is usually suggested. If nothing else can be done this could be considered as a first step to achieve the Hydro flotation effect.

 

B/ Small quantities: hypertonic solutions 32% Dextran (Hyskon®) Because of the side effects, anaphylactic shock,  this solution has been abandoned.

 

 

·  Hydro flotation

 

·  Barrier principles

 

·  Pharmacological agent

 

Examples are:

 

·  Fibrin glue: Intergel®, Adept®

 

·  Fibrin sealant: Tissucol®

 

·  Spray-Gel ^TM

 

Although the results indicate that the number and the extend of adhesions can be reduced the results are still inconsistent. (22).

 

 

 

There are a great number of solid barriers but if they are permanent barriers they require yet another intervention to take them out or if they are not permanent they cannot be used when there is still some bleeding within the operating field. Some are difficult to handle through the laparoscope i.e. Interceed®

 

 

 

 

This boils down to the inhibition of the inflammatory reaction. Various drugs have been used intra abdominally and systemic (corticosteroids-calcium channel blockers - non- steroid anti inflammatory drugs (NSAID) - histamine antagonists - antibiotics - antioxidants - progesterone - colchicines and selective immune suppressors. In animal studies some of these drugs did have a beneficial effect but data in the human are scarce.

 

 

 

 

Another cause of trauma is the hypoxiaemia caused by the use of CO₂ gas in large quantities and the pressure of the pneumo peritoneum itself (usually set at 15 mm Hg) . The low oxygen concentration in the tissues that follows, hypoxia, alters the metabolism of the endothelial cells and increases the vascular permeability. It also starts an increased expression of adhesion molecules such as vascular cell adhesion molecule (VCAM)-1 and intra cellular adhesion molecule (ICAM)-1 and an increased polymorphonuclear (PMN) adhesion to the vascular endothelium. Hypoxia also could up-regulate plasminogen activator inhibitor-1 (PAI-1) and down regulate tissue-type plasminogen activator (t-PA) thus decreasing the plasmin and in doing so inhibiting the lysis of fibrin. The effect of mesothelial hypoxemia- induced during laparoscopy by the use of CO₂ to create a pneumo peritoneum - upon vascular endothelial growth factor (VEGF) expression can be considered to explain an increase in adhesion formation (23).

 

It could therefore be wise to consider a mixture of CO₂ and 3% O₂ for the creation of the pneumo peritonea, although this 3 % is not enough to sustain intact metabolism of the mesothelial cells. A solution could be the gasless laparoscopy although care here should be taken not to crush the peritoneum over large surface areas.

 

 

 

 

 

Laparoscopic surgery decreases the number of de novo adhesions especially when used in combination with the microsurgical techniques. The number and extension of adhesions after conventional surgery does not alter after laparoscopic lyses. Barriers and medication are to be considered and studied in the future. The impact of the pneumoperitoneum on the peritoneum is not as harmless as we thought; therefore preventive steps should be taken to minimize this impact in mixing the carbon dioxide with 3% of oxygen and moistening the mixture at the entrance of the abdomen. The second look laparoscopy seems to become a must, although more clinical data are needed, when we consider cost benefits on the background of the readmissions and the increase in difficulty of a re intervention and the increase in theatre time of the re intervention. A second look laparoscopy should be carried out on day eight after the primary operation.

 

 

 

The author wishes to thank Bart.W.J. Hellebrekers MD, PhD, for letting the authors use his PhD thesis “ Intra-abdominal Adhesion Formation and the Fibrinolytic System” Thesis defended at the university of Leiden 2002. Thanks also to Roger Molinas (CHT KU Leuven Professor Philippe Koninckx) who let the author have an insight in his latest experimental work on adhesion formation.

 

 

 

1 Holtz G. Prevention and management of peritoneal adhesions. Fertil Steril 1984; 41:497-507.

 

2 Trimbos-Kemper TCM, Trimbos JB, Van Hall EV. Adhesion formation in tubal surgery: results of the eight-day laparoscopy in 188 patients. Fertil Steril 1985;43:395-400.

 

3 Homdahl L. The Lancet, 353, May, 1, 1999.

 

4 Diamond MP, Daniell JF, Feste J.Adhesion formation and de novo adhesion formation after pelvic surgery. Fertil Steril 1987; 47:846-6.

 

5 Lundorff, Hahlin M, Kallfelt B, Thorburn J, Lindblom B. Adhesion formation after laparoscopic surgery in tubal pregnancy: a randomised trial versus laparotomy. Fertil Steril 1991; 55:911-5.

 

6 Operative Laparoscopy Study Group. Postoperative adhesion development after operative laparoscopy:evaluation at early second look procedures. Fertil Steril 1991; 55:700-4.

 

7 McEntree G, Pender D, Mulvin D, McCullough M, Naeeder S, Farah S, Badurdeen MS, Ferraro V, Cham N. Current spectrum of intestinal obstruction. Br J Surg 1987;74:976-80.

 

8 Steege JF, Stout AL. Resolution of chronic pelvic pain after laparoscopic lysis of adhesions. Am J Obst Gyn 1991;165:278-81.

 

9 Gomel V. An Odyssey through the oviduct. Fertil Steril 1983;39:144-56.

 

10 Diamond MP, Hershlag A. Adhesion formation/reformation. Prog Clin Biol Res 1990;358:23-33.

 

11 de Lange DCD, Jeekel J. Prevalence of adhesions and the associated costs in general surgery . In: deZerega G (ed), Peritoneal surgery. Springer Verlag, New York 2000;307-21.

 

12 Bakkum EA, Emeis JJ, Dalmeijer RAJ, van Blitterswijk CA, Trimbos JB, Trimbos-Kemper TCM. Long-term analysis of peritoneal plaminogen activator activity and adhesion formation after surgical trauma in the rat model. Fertil Steril 1996;66:1018-22.

 

13 Vipond MN, Whawell SA, Topson JN, Dudley HAF. Peritoneal fibrinolytic activity and intra-abdominal adhesions. lancet 1990;334:1120-2.

 

14 Von Benzer H, Blumel G, Piza F. Uber Zusammenhänge zwischen Fibrinolyse und intraperitonealen Adhäsionen. Wien Klin Wschr 1963;75:881-8.)

 

15 Boys F. The prophylaxis of peritoneal adhesions. A review of the literature. Surgery 1942; 11:118-68.)

 

16 Matas R, Miller RT,Heuer GJ. In memoriam William Steward Halsted: 1852-1925. Arch Surg 1925;10:293-305.

 

17 Siegler AM, Kontoupoulos V. An analysis of macro surgical and microsurgical techniques in the management of the tuboperitoneal factor in infertility. Fertil Steril 1979;32:377-83.

 

18 Duffy DM, diZerega GS. Is peritoneal closure necessary? Obstet Gynecol Surv 1994;49:817-22.

 

19 Lundorff P, Hahlin M, Kallfelt B, Thornburn J, Lindblom B. Adhesion formation after laparoscopic surgery in tubal pregnancy: a randomised trial versus laparotomy. Fertil Steril 1991; 55:911-5.

 

20 Jansen RPS. Failure of peritoneal irrigation with heparin during pelvic operations upon young women to reduce adhesions. Surg Gynecol Obstet 1988; 166:154-60.

 

21 Stapel A, Geissler N, Mlaskowsky B, Jung D. Behavior of postoperative adhesions after intraperitoneal administration of fibrinolytic drugs in a rat model. Langenbecks Arch Chir 1997; 382:1:33-6.

 

22 Johns DB, Keyport GM, Hoehler F, diZerega GS. Reduction of post-surgical adhesions with Intergel adhesion prevention solution: a multicenter study of safety and efficacy after conservative gynaecologic surgery. Fertil Steril 2001; 76: 595-604.

 

23 Molinas CR, Koninckx PR. Hypoxaemia induced by CO₂ or Helium pneumoperitoneum is a co-factor in adhesion formation in rabbits.Hum Reprod 2000;15:8:1758-1763.