After Scar II

Self explanatory
The steps leading to the formation of adhesions and some of the factors that can influence the development of adhesions during surgery are illustrated.
How adhesions develop:
The tissue surface becomes damaged, either through surgery or injury, leading to disruption of the mesothelial lining
Bleeding and leakage of plasma proteins lead to fibrin deposits at injured sites, which is augmented by post-traumatic inflammation
The enlarging fibrin mesh might attach to an adjoining surface, a process that is counteracted by locally generated fibrinolytic factors
Depending on local peritoneal conditions, the fibrin mesh could either be degraded, resulting in scarless repair, or transformed into an adhesion consisting of connective tissue
If the fibrin is degraded within the first few days, the defect heals scarlessly
If remnants of fibrin remain for long enough, recruited reparative cells transform the initially reversible fibrinous adhesion to a fibrous, collagen-containing structure
Various factors can influence the development of adhesions during surgery - e.g. infection, heat, light, glove powder.
From the basic processes that result in the formation of adhesions, there are various steps that can be taken during surgery to minimise the risk of adhesions
These are:
increase vascular permeability
reduce infection risk
avoid GI contamination
minimise tissue handling by careful technique and microsurgery
reduce drying of tissues by using lubrication
limit use of cautery
limit use of sutures
avoid materials with fibres
use starch-free gloves
Although these measures will minimise the risks, they cannot eliminate the problem completely
Thus there is a clear need for improved adhesion-reduction strategies
Adhesion-reduction strategies involve:
Careful surgical technique
Minimisation of inflammatory response by use of
corticosteroids
NSAIDs
antibiotics
Augmentation of fibrinolysis
tissue plasminogen activator
Use of various adhesion-reduction agents
Risberg B. Eur J Surg 1997;577:32-39
Risberg reviewed a number of adhesion prevention strategies and techniques. The two major prevention strategies discussed are (1) adjusting surgical technique and (2) application of adjuvants.
NSAIDs (e.g. ibuprofen, tolmetin and oxyphenbutazone) can be applied systematically as well as intraperitoneally. Clinically efficacy remains questionable possibly because of drug delivery difficulties.
Corticosteroids (dexamethasone, hydrocortisone and prednisolone) can be administered intraperitoneally. Efficacy is doubtful due to associations with immunosuppression and delayed wound healing, e.g. infection, incisional hernia and wound dehiscence. Also, they do not remain in the peritoneal cavity for the duration of adhesion formation (4-5 days post surgery)
Fibrinolytics are designed to prevent or reverse fibrin deposition. Intraperitoneally or systematically administered plasminogen activator (tPA), streptokinase and elastase have undergone considerable laboratory evaluation with conflicting results, and in some cases, haemorrhagic complications. This lack of efficacy may be attributable to the problem of rapid peritoneal absorption and clearance.
To assess European opinion on post-operative adhesions two surveys were conducted, one at ESHRE 2002 (European Society of Human Reproduction and Embryology) and EACP (European Association of Coloproctology).
The respondents from ESHRE were all gynaecologists and results were as follows:
14.2% of respondents cited safety as an attribute associated with an ideal anti-adhesion agent
13.4% cited effectiveness
36.2% cited ease of use
15.7% cited low cost
Published in ANV 4
Note:
Preclude is referenced as ‘generally unavailable’ as clinical experience shows there are limitations in its use.
Hyskon is included in this slide as there is anecdotal evidence to suggest off-license use. However, cases of anaphylaxis have been recorded.
Mathias Korell – well recognised German gynae laparoscopy specialist has done studies with Spraygel and uses in endometriosis cases – where they do a lot of surgery (like colorectal in terms of extent of work in the abdomen – ie not neat and dainty stuff) and he is quoting need 5 kits to then coat the peritoneum to ensure adequate coverage – will be in Adhesions News & Vies Issue 5
Cost they quote around £150/sheet that would be a good size in abdominal surgery – but they won’t be more specific or detail how many sheets a colorectal surgeon might need to use
Adept® (icodextrin 4%) is a new potential solution to adhesions
Adept is approved throughout Europe for use in abdominal and pelvic surgery as an intraoperative wash and postoperative instillate for the reduction of adhesions
It is available as a 1 litre bag and most recently as a 1.5 litre bag to allow use of one bag for irrigating during surgery and to provide 1000ml to leave behind as a postoperative instillate
Work from a registry of routine use (ARIEL) which is now progressing in 150+ centres in Europe showed that a 1.5 litre presentation of Adept would be useful for most surgical cases allowing surgeons to irrigate with up to 500ml during surgery and then instil 1000ml to leave behind at the end of surgery
Icodextrin is a  1,4 linked glucose polymer
The structure is different from Dextran; the key difference lies in the linkage of carbon 1 and 4 (versus Dextran 1,6 which the human body cannot break down easily)
Icodextrin was developed from hydrolysis of corn starch (so it is a natural product)
Icodextrin is used for adhesion reduction as a 4% solution
This 4% solution is isosmolar and biocompatible with other drugs
Icodextrin is a large polymer and attracts a ‘water of hydration’ around it, increasing its size still further.
It is absorbed from the abdomino–pelvic cavity by the lymphatic system. In the blood it is broken down readily by amylase (acts on the 1,4 link) to maltose/isomaltose and then glucose, and is then excreted
Icodextrin has a well-established safety profile at the higher concentration of 7.5% where it is used in peritoneal dialysis - with > 36,000 patient years of safety data and use of Adept in >50,000 as at end January
Icodextrin was developed originally to overcome the issues associated with existing peritoneal dialysis fluids, specifically irritation to the peritoneum, etc
As a result of its structure, icodextrin with its ‘water of hydration’ stays in the abdomino–pelvic cavity over time (it is absorbed solely by the lymphatic system). It is this persisting presence in the abdomino–pelvic cavity that is thought to reduce adhesion formation/reformation as a result of ‘hydroflotation’
Hydroflotation is not a new concept, but the problem has been in finding a fluid that would stay in the abdomino–pelvic cavity long enough to keep tissues apart in the critical time after surgery when adhesions develop, but which does not have an irritant effect on the peritoneum, nor causes problems when absorbed (e.g. Dextran)
This slide looks at the persistence of 4% icodextrin over time compared to saline and glucose
It comes from a study in patients receiving peritoneal chemotherapy in whom 4% icodextrin was used as the carrier fluid1. In the periods between chemotherapy the icodextrin was used as a ‘dwell’ and aliquots drawn off through the Tenckhoff catheter
The results show that 50% of the icodextrin 4% solution was still retained after ~92+ hours, whereas within a day all the saline or glucose was absorbed by the lymphatics
This is the reason why crystalloid solutions such as saline are not very effective in the reduction of adhesions, as they do not stay in the abdomen for long enough to keep the organs and tissues ‘hydroflotated’
Reference
1. Hosie K, Gilbert JA, Kerr D et al. Fluid dynamics in man of an intraperitoneal drug delivery solution: 4% icodextrin. Drug Delivery 2001; 8: 9–12.
Video clips showing instillation at end of surgery
This slide shows the cost comparison of recent agents at current UK prices
Note the costs of agents is different in Finland but comparatively the relative price differentials will be the same
Two kits of Spraygel are often used to get adequate coverage of the surgical site and as per Prof Mathias Korell’s experience in major gynaecological surgery – 5 kits may be needed to ensure adequate coverage of the peritoneal cavity!
The US outcomes study with Seprafilm is using a mean 4.4 sheets/patients1
Intergel was withdrawn in April 2003
Reference
1. Beck DE, Cohen Z, Fleshman JW, Kaufman HS, vanGoor H, Wolff BG. Prospective, randomized, multicentre, controlled study of the safety of Seprafilm Adhesion Barrier in abdominopelvic surgery. Dis Colon Rectum 2003
This slide shows the cost comparison of recent agents at current UK prices illustrating costs of using 4.4 sheets Seprafilm (as per Beck) and 5 kits of Spraygel as (per Korell).
SurgiWrap not included as they don’t give a precise list price or how many sheets are used – when asked – and ?? Anyone using it yet??
Wilson MS et al. Colorectal Disease 2002;4:355-360
Wilson et al. modelled data from a lower abdominal surgery cohort from the SCAR data to assess cost effectiveness.
Results showed that:
Routine use of adhesion reduction products costing £50 per patient will payback the cost for such investment if they reduce adhesion-related readmissions by 16% after 3 years
A product costing £200 will need to offer a 64.1% reduction in readmissions after 3 years to recoup its direct costs
For the estimated 158,000 lower abdominal surgery operations conducted in the UK each year the cumulative costs of adhesion related readmissions over 10 years are estimated at £569 million
At year 3 – 64% reduction would be needed
And at 3 years
Wilson MS et al. Colorectal Disease 2002;4:355-360
Wilson et al. modelled data from a lower abdominal surgery cohort from the SCAR data to assess cost effectiveness.
Results showed that:
Routine use of adhesion reduction products costing £50 per patient will payback the cost for such investment if they reduce adhesion-related readmissions by 16% after 3 years
A product costing £200 will need to offer a 64.1% reduction in readmissions after 3 years to recoup its direct costs
For the estimated 158,000 lower abdominal surgery operations conducted in the UK each year the cumulative costs of adhesion related readmissions over 10 years are estimated at £569 million
This slide looks at cumulative costs of using an adhesion reduction agent over 9 years scaling up to the UK as a whole.
Using a £50 agent with a 25% efficacy would result in a saving of £71m
But using a £200 product with similar efficacy would result in a £142m loss – ie the health system would have to spend an extra £142m over the 9 years to reduce adhesion related readmissions by 25%.
In only 10.4% of cases were adhesions mentioned as part of the informed consent process
14.4% adhesions were discussed but not part of the consent
In those undergoing specific adhesiolysis operations 54% of patients reported being given some kind of information on adhesions before surgery
46% were given information on anti-adhesion agents
In procedures not involving adhesiolysis only 10% of patients reported receiving any adhesion information
Only 6% of cases were given information on anti-adhesion agents
Is this acceptable practice?
Most common adhesion-related claims
Failure to diagnose adhesion-related problems
Delay in diagnosis
Bowel damage at adhesiolysis
– laparoscopy > laparotomy
Infertility or risk of infertility
Starch granuloma – (use of starch-powdered gloves)
Failure to take precautions to prevent adhesions
1994 -1999 UK Medical Defence Union received 77 adhesion-related claims
Out of court settlements in 14 cases in 11 years ranged from £7960 - £124,261 (~€11,701 - €182,664)
– average £50,765 (€74,625)/case
And that was up until 1999
Since 1999
More evidence of burden of adhesions
SCAR study
Van Krabben enterotomy risk
SCAR-2
etc
Discuss high risk options then lead to prohylaxis

Before SCAR
Before we knew the real extent of the problem
Before we had newer anti-adhesion agents
Adhesions continue to be a significant burden
For the patient:
pain, SBO, infertility, re-operative complications
For the surgeon
increased workload, lengthy and complex procedures, medicolegal consequences
For the healthcare system
increased workloads, costs, bed stay

Where are we now?
Any advances in surgery have had little impact
Action on adhesions has received low priority
even in high risk procedures
New developments in anti-adhesion agents

not all are difficult or costly to use
emerging evidence of efficacy
Adopt use of anti-adhesion agents in ‘High Risk’ surgery
Adhesiolysis
Small bowel resection
Formation of stoma
Hartmann’s procedure
Anterior resection
Abdomino-perineal excision
Colectomy
Surgical treatment of peritonitis & fistulae

Thank you
Fellow SCAR Panel Members
Prof Harold Ellis, UMDS, London
Malcolm Wilson, Christie Hospital, Manchester
Don Menzies, Colchester Hospital, Colchester
Jeremy Thompson, Chelsea & Westminster Hospital, London
Brendan Moran, North Hampshire Hospital, Hampshire
Adrian Lower, St Bartholomew's Hospital, London
Rob Hawthorn, Southern General Hospital, Glasgow
Prof Alastair McGuire, City University, London
Graham Sunderland, Southern General Hospital, Glasgow
David Clark, James Boyd, Alan Finlayson, ISD, NHS Scotland, Edinburgh
Prof Ian Ford, Robertson Centre Biostatistics, Glasgow
Alastair Knight & Alison Crowe, Corvus
Shire Pharmaceuticals Group plc
Powerpoint template

Please read more
http://www.euuzlet.hu/koloproktologus/2004/parker.ppt.