SIRG minutes - 4 October 2000

Silicone Gel Breast Implants: Independent Review Group Meeting
4 October 2000, Hannibal House, Elephant and Castle

Present:
Professor R Sturrock (Chairman)
Professor R Batchelor
Mrs V Harpwood
Professor D London
Mr T Milward
Professor A Silman
Professor R Walker

Secretariat:
Dr A Austin
Mr G A Crosbie
Dr D M Gott
Dr S Ludgate
Mr J Tinkler

Apologies:
Ms C Rayner

1. Introduction
The Chairman welcomed all members of the Group present. Ms Rayner was unable to attend and her apologies were noted. The Chairman expressed deep sadness and sympathy over the death of Professor Sloane. The Chairman wished to record his and the IRG’s gratitude for Professor Sloane’s contribution to their work. He then welcomed Professor Walker to her first meeting.

2. Minutes of the last meeting
The minutes of the previous meeting held on the 9 March (SIRG(00)35) were confirmed after the insertion for clarity of the year into the date in the header. These had been agreed by IRG members by correspondence before their publication on the IRG Website.

3. Matters arising
All matters arising from the minutes of the last meeting were covered by the Agenda.

4. Membership of Group
It was confirmed that Dr Judy Evans had withdrawn from the IRG. Professor Walker had joined the IRG to provide expertise in pathology in succession to Professor Sloane. It was agreed that membership of the group should be reviewed following the IRG Open Meeting on 5 October.

5. Update on the recommendations (SIRG(00)75)
5.1 Recommendations 1,3,4 - Patient information leaflet
The patient information leaflet produced by the group chaired by Baroness Emerton would be launched at the IRG Open Meeting on 5 October. Mrs Harpwood noted that she had participated in the Emerton group and that there had been dialogue between all interested parties. Mr Milward expressed concern that inclusion of the British Association of Cosmetic Surgeons (BACS) might be perceived as conferring on them an official endorsement that is not warranted given the uncertain membership criteria and training requirements of BACS. It was noted that plastic surgeons and surgical oncologists were more conscious of psychological issues than other surgical specialties and would be able to provide appropriate counseling.

Both the British Association of Plastic Surgeons (BAPS) and the British Association of Aesthetic Plastic Surgeons (BAAPS) supported the recommendations regarding consultation. Mr Milward expressed concern that problems could still occur within segments of the private sector. Mrs Harpwood noted that this may be ameliorated since the patient information leaflet would be available to all women and included a checklist of issues for the consultation. The Royal College of Surgeons had developed Good Practice Guidelines (GPG) in breast implant surgery including the issue of consent.

5.2 Recommendation 2 - Advertisements
The Department of Health had held discussions with the Advertising Standards Authority.

5.3 Recommendation 5 - Private Sector
The IRG noted that the Care Standards Act was on the statute book and the Department of Health was developing the required standards for implementation of this legislation.

5.4 Recommendation 6 - NBIR Steering Group, Actions and Proposals
The Chairman reminded members that it had not been possible to make registration compulsory and that this had been reinforced by recent developments such as the requirements of the Data Protection Act, the Human Rights Act and the GMC guidelines on consent. There was an increase in compliance measurements and steps to encourage registration. Professor Silman noted that some measure of the extent of non-registration was required. A consent form developed by the NBIR Steering Group was been sent to professional bodies for comment and may assist in estimating compliance.

5.5 Recommendation 7 – Guidance on adverse incident reporting.
The Medical Devices Agency had published guidelines in 1999. These had been sent to all members of BAPS and BAAPS and every center registering patients on the NBIR. In addition these had been reflected in the RCS Guidelines. Mr Milward suggested that plastic surgeons needed to be frequently reminded of the contents of this guidance.

5.6 Recommendation 8 - Research
The Research and Development Directorate had advertised for tenders to undertake a pilot project using the NBIR.

6. Breast implants and mammography (SIRG(00)36)
The IRG noted the information from the NHS Breast Screening Programme on the effect of breast implants on mammography and breast cancer screening. It was noted that breast implants could interfere with mammography but that these difficulties could be overcome by use of appropriate techniques if the radiographer was informed of the presence of breast implants. Mrs Harpwood expressed concern that women were insufficiently informed about the requirement to inform their radiographer. Professor London and Professor Batchelor referred to a recent article in the British Medical Journal on breast cancer detection, the Secretariat will circulate this article. It was agreed that information on breast implants and mammography should be provided on the IRG website including a link to any advice from the NHS Breast Screening Programme.

7. Indemnity
Dr Ludgate informed members that indemnity had been agreed and provided members with a letter confirming this for their records.

8. Adverse incident reports to MDA
The number of new reports was lower than in previous periods and most were related to recent events. No trends were discernable from these reports in regard to generic issues or any particular model.

9. NBIR Annual report 1999
The IRG noted the report and the increase in the number of registrations compared to previous years.

10. Scientific Papers: Discussion and Update (SIRG(00)43-70, SIRG(00)78-80, SIRG(00)81 and SIRG(00)85)
The Chairman reminded members that they should submit their comments on scientific papers to the Secretariat for compilation. The IRG’s comments on these reviewed papers are attached as an annex to these minutes.

Members present agreed that these papers did not alter the IRG's original conclusions, but one or two papers had identified areas that required continued monitoring. Mrs Harpwood noted that the papers describing the experience of expert panels highlighted a difference between the US and British courts, namely that the first duty of expert witnesses in the UK was to the court rather than either side in the case. Professor Silman drew attention to the meta-analysis published in the New England Journal of Medicine, this was a very good paper which addressed the criticisms of the sample size in individual studies. Professor Batchelor noted that the recent paper reporting the lack of antibodies to silicone was reassuring, this paper highlighted the need to be alert to storage effects on immunoglobulins.

11. EU activity on breast implants (SIRG(00)71)
The IRG noted the contents of the Scientific and Technological Options Appraisal report for the European Parliament and the subsequent discussions within the European Parliament. The recommendations arising from these were consistent with the IRG’s recommendations.

12. Correspondence concerning the IRG relating to:
Remploy (SIRG(00)38)
Further correspondence relating to Remploy has been received. The IRG noted that the position was unchanged since the discussion at the last meeting (see minutes of the October 1999 meeting SIRG(99)44 for details).

Safety of Silicone Gel Breast Implants (SIRG(00)29)
Further correspondence from members of the public and their MPs were received which related to individuals’ experiences following breast implant surgery. The IRG again noted that the letters often contained very detailed descriptions of distressing personal problems and ill heath but they did not contain any information to alter the conclusions it had drawn in 1998.

Trilucent breast implants (SIRG(00)40)
Several letters had been received contrasting the action taken by the Medical Devices Agency with regard to Trilucent breast implants with the perceived inactivity on silicone gel breast implants. The IRG noted that Trilucent breast implants were outwith their remit and that these actions were taken following the analysis of the relevant information and associated risks by independent experts.

13. Preparations for the IRG open meeting on 5 October
The Secretariat outlined the administrative arrangements for the meeting. The Chairman and members had an extensive discussion of all the questions received prior to the meeting and agreed which member of the IRG should respond and the outline of each response.

14. Date of next meeting
The date of the next meeting was arranged for 14 December 2000.

Annex 1 : Recently published literature : Summaries provided by IRG members

Expert Witnesses in the US

Price JM and Rosenburg ES, "The SGBI Controversy: The Rise of Expert Panels and The Fall of Junk Science." Journal of The Royal Society of Medicine 324: 31-34 (2000) [SIRG (00)43]
This article updated the events surrounding the litigation in the US concerning SGBI, and explains the role of scientific panels appointed by the Courts in the United Stated in the SGBI litigation there.

The article points out that despite a large number of scientific studies that have failed to reveal any association between SGBI and various connective tissue diseases, lawsuits are still being brought in the US. There had, as is well know, been several successful claims before lay juries who tended to be swayed by emotional issues instead of taking the scientific evidence properly into account. Such juries find it difficult to distinguish between junk science and good science. As recently as January 1999, a federal jury in Washington DC awarded a woman ten million dollars.

Such cases have drawn the attention of the legal and scientific communities to the fallibility of juries, and the law in the US has recently changed. The previous rule laid down in Frye v United States (1923) was that scientific evidence would only be admissible if it observed principles and methods generally accepted by the scientific community in question (similar to the well-known Bolam test in UK law).

However, the approach was changed in 1993, and now more emphasis is paced on the role of the judges. In 1993, the case of Daubert et al v Merrell Dow Pharmaceuticals laid down new guidelines requiring judges to take on the role of gatekeepers scientific evidence. That was a Supreme Court decision concerning the possible role of a drug in causing birth defects. Judges must, in accordance with the guidance, decide whether the expert scientific evidence is both scientific and relevant. Federal judges must now undertake "A preliminary assessment of whether the testimonies underlying reasoning or methodology is scientifically valid and properly can be applied to the facts at issue."

Such evidence can only be admitted in the course of proceedings if it is founded on the "methods and procedures of science". So judges appoint scientific panels to advise and assist them. In the US, judges have for some time had the authority under the Federal Rules of Evidence to appoint witnesses selected by them. This applies in all States, so that litigation has been standardised in this respect. Counsel for both sides in a particular case must approve the experts to be used on the panel.

Several judges have appointed independent scientific panels to review the scientific evidence in SGBI cases and to report their views to them. For example, Judge Robert Jones of the US District Court in Portland Oregon, after taking advice from a scientific panel, concluded that the "junk science" experts should be excluded from the case. Judge Jack Weinstein of the US District Court for the Eastern District of New York, arrived at a similar conclusion, stating that after analysing the report of his scientific advisers there had been a failure to prove that SGBI cause any syndromes complained of.

Judge Sam Pointer Jnr, the senior judge overseeing all federal cases on SGBI at the pre-trial stage, decided that appointing such a panel was the only sensible and practical means of obtaining unbiased scientific evidence about the effects of SGBI. Accordingly, he appointed his own scientific panel under Rule 706 of the Federal Rule of Procedure. That panel consisted of four experts – a rheumatologist, an epidemiologist, an immunologist and a toxicologist. Their brief was to determine the extent to which "existing studies, research and reported observations provided a reliable and reasonable basis for one to conclude that SGBI cause or exacerbate" the conditions in question. After two years exhaustive work, the panel stated that it had examined over 2000 documents submitted by counsel for both sides, and concluded that the evidence indicated that "SGBI do not alter the incidence or severity of autoimmune disease…..There is no evidence that SGBI precipitate novel immune responses or undue systemic inflammation. And continued "no association was evident between breast implants and any of the individual connective tissue diseases, all definite connective tissue diseases combined, or the other auto-immune/rheumatic conditions".

The evidence of the UK Independent Review Group was strongly influential to the panel in arriving at this conclusion.

One important point is that the panel had been given the particular task of advising the judge whether the panel’s opinions were "subject to sufficient genuine dispute as would permit other persons, generally qualified in your field of expertise, to express opinions that, though contrary to yours, would be likely to be viewed by others in the field as representing a legitimate and responsible disagreement within your profession".

The panel advised that the vast majority of their colleagues would agree with their findings, but that there may be a few individuals who might disagree with some of their findings.

The article concludes with the observation that there is unlikely to be a swift end to the SGBI controversy. Too many lawyers and experts are making too much money out of it, and too many women have been frightened. The authors recommend that the scientific panels be used in all future litigation on breast implants, and that the same principles should apply in other cases involving technical expert evidence.

Hulka BS, Kerkvliet NL and Tugwell P; "Experience of a Scientific Panel Formed To Advise the Federal Judiciary On SGBI". New England Journal of Medicine 324: 812-815(2000) [SIRG (00)44]
This article explains that the working of the new system of using scientific panels is not without problems. It was written by three of the members of the scientific panel established by Judge Sam Pointer Jnr in 1996 in Re SGBI Product Liability Litigation. The scientific panel members were clearly rather unhappy about their role. They expressed misgivings about the impact of the legal process, and matters such as discovery of documents, on their work as panellists. All panel work in progress, including notes, comments and interim drafts, had to be produced if required, because it was held to be within the scope of legal discovery and were used for legal manoeuvring during subsequent depositions. Judge Pointer was concerned because of what he describes as "cultural chasm" between the approach of those in the scientific community and that of those involved in litigation. The final report of the panel was favourably received by the scientific community, and it had an effect on pending litigation, preventing people relying on "junk science". In the event the panel members accepted the need for such panels where the scientific evidence was complex because they can "bring unbiased evidence into the court room".

IRG comments on whether such a system could/should apply in the UK under the present procedural rules?
As personal injury cases are not decided by juries in the UK, there is much less opportunity for good advocates and experts witnesses to succeed in claims based on "junk science". It is usually possible to rely on our judges to weigh the scientific evidence carefully and to reach balanced conclusions, though there are glaring example in the past even of the Court of Appeal being swayed by dubious scientific explanations (Roe v Minister of Health 1951).

It is certainly worth considering whether judges would benefit from the assistance of expert panels similar to those used in the United States. Indeed, it has been suggested that clinical negligence claims be decided by panels of people who include a judge and medical assessors, though at present this system is very unlikely to be implemented

There are already certain features of our legal system that indicate a shift towards the US procedures. The new Civil Procedure Rules, introduced in April 1999, allow judges to be much more proactive in the conduct of proceedings, including the pre-trial stage. For example, no expert can be used without the permission of the Court. Experts must set out in their reports the substance of their instructions. Experts must meet to thrash out the issues, and the judge has power to order them to do so. The parties are encouraged to use single joint experts if possible, and in certain circumstances the judge can select a medical or other expert from a panel of experts kept by the Court if the parties cannot agreed between themselves. This however, is not the usual practice in clinical negligence cases, where there are frequently complex issues to be decided, and the parties are currently given greater leeway to select and use their own experts.

Another important feature of the Civil Procedure Rules is that the duties of experts are spelled out clearly. These include the requirement that experts owe an overriding duty to the Court, and this has priority over the duty to the Party giving the instructions and paying the fee. Experts must sign a declaration acknowledging this duty, and stating that the opinions expressed in their reports are correct, and that the facts stated are true. This cultural change makes it more difficult for unscrupulous scientific experts to be partisan.

Substantive law in the UK has also been changed by a modification of the rule in Bolam v Friern Hospital (1957). The Bolam test used to provide doctors with substantial protection from a finding of negligence where the expert witnesses disagreed. As long as the defendant doctor whose conduct was in question was able to find an expert witness to testify that there was a responsible body of medical opinion that would support what he did, the judge could not make a finding of negligence. This was so even if the expert for the claimant testified that there was a body of opinion that would disagree. This rule was modified by the House of Lords in the case of Bolitho v City and Hackney Health Authority in 1997. Under the new rule, the judge is permitted to choose between two expert opinions if one appears to him or her to be "logically indefensible". This means that judges are now better equipped to reject expert scientific or medical evidence that they consider to be suspect.

On balance, it is probably safe to conclude that the UK system, in the light of recent developments, already accommodates mechanisms for rejecting "junk science". However, there may be a case for appointing panels of scientific experts where the evidence is particularly complex.

Clinical studies – case reports, case series, controlled clinical studies and epidemiology
Brown S.L, Middleton M.S., Berg W.A., Soo M.S. and Pennello G.; Prevalence of rupture of silicone gel breast.implants revealed on MR imaging in a population of women in Birmingham, Alabama,. American Journal of Roentgenology 2000; 175 1057-1064 [SIRG(00)85]

Objective To determine the prevalence of MRI-ascertained rupture in implanted women, MRI being a more sensitive measure

Methods 344 woman, 687 implants, MRI scored by 3 radiologists with good agreement on findings, rupture defined as gel outside the implant. Predictors of rupture assessed

Results 55% of implants and 69% of women had a rupture, higher if possible ruptures considered. Proportion related to duration since implant and to location, worse in submuscular. Results unlikely to be explained by responder bias

IRG Comment A well conducted study, carefully analysed and interpreted. Implants were mostly pre 1988, ie many would predate the 3rd generation of implants? Their definition may be too sensitive, though good arguments presented

Brown S L, Middleton M S, Berg W A, Soo M S & Pennello G; Study Of Silicone-Gel Filled Breast Implant Rupture (MRI Component). FDA website. (2000)[SIRG (00)63]
907 women from two plastic surgery practices were contacted concerning implants. The survey revealed that one third of them had had their implants removed and replaced following the original operation. 344 women were randomly selected (687 implants) for MRI scanning. Of these 82% had normal gel-filled implants and 18% had double-lumen saline/gel implants. The MRI scans were assessed by 3 radiologists independently with a very high agreement rate. This revealed 55% of ruptured implants with 69% of patients having at lease one ruptured implant. 12% of the ruptures were extracapsular. The age of the implants averaged 17+/-3 years. There were a variety of implants used. The types were not identified.

This is a general interest paper but not controlled in any particular way. No direct implications can be taken from this data about the behaviour of any particular implant or factors increasing or lessening rupture rate. This study is the same as the MRI one by Brown et al see above, on the same women.

Brown, Middleton et al; FDA Study of Breast Implant Rupture and Reoperation in Augmentation Cohort – Sixth World Biomaterials Congress Transactions (2000) [SIRG (00)64]
This is a very brief summary of the previous paper and adds nothing to the previous paper.

Janowsky E C, Kupper L L & Hulka B S; Meta-Analyses Of The Relation Between Silicone Breast Implants And The Risk Of Connective-Tissue Diseases. New England Journal Of Medicine 342: 781-790 (2000) SIRG (00)45
Summary: This important paper reports of the results on a meta-analysis of all studies investigating a possible association between silicone breast implants and the following connective tissue diseases (CTD): rheumatoid arthritis, systematic lupus erythematosus (SLE), Scleroderma, Sjogren’s syndrome and various combinations of disorders. Data from nine cohort and eleven cross-sectional or case-control studies were analysed. Apart from Sjogren’s syndrome, this analysis excluded any important association with the other disorders examined.

Originality: Meta-analysis is a useful technique which statistically summarises the date from studies addressing the same major question. It is particularly appropriate in the situation where individual studies are not large enough to produce robust estimates of the size of an association. Demonstrating a lack of an association in situations where either the exposure or the disease is rare is particularly difficult as is the case with silicone implants and CTD. Pooling of studies using meta-analysis has the potential of generating a very narrow confidence interval, around an effect estimate of approximately unity, giving increased confidence that no important effect has been missed.

Three previous meta-analysis have been published, all of which failed to find an association between CTD’s and implants. The current report is different, and is an improvement, in the following respects:

1. It includes eight new studies published since the most recent previous meta-analysis.
2. It analysed separately the association with silicone-gel filled implants.
3. Its analytical approach allowed for potential differences (heterogeneity) in the result of the available studies.

Methods: An exhaustive literature search revealed nine cohort studies (comparing the longitudinal risk of CTD in women with implants with those without implants), nine case-control and two cross-sectional studies examining the frequency of implants in various CTD groups of women and controls. The largest by Hennekens et al, was by far the largest case-control study, but relied on self-reported diagnosis. The major analyses were undertaken on (1) all studies and (2) after excluding the data by Hennekens et al.

Results: The major results are summarised in the Table below.

The results show no evidence of any association. Analyses undertaken including the data by Hennekens et al made very little difference to this conclusion.

IRG Comments: In some analyses, there was a suggestion of a possible association with Sjogren’s Syndrome. Including the Hennekens data gave a summary relative risk of 1.47 (95% CI 1.01-2.14). This disorder is difficult to detect in surveys and the inclusion of the Hennekens case-control data would be consistent with a diagnostic misclassification bias. There is no evidence of any effect with any other disorder studied. Given this weight of negative evidence, it is unlikely that further epidemiological studies of the risks for this group of diseases in women with silicone implants would be undertaken or necessary.

Brinton L A, Brown S L, Colton T, Burich M C & Lubin J; Characteristics Of A Population Of Women With Breast Implants Compared With Women Seeking Other Types Of Plastic Surgery. Plast-Reconstr-Surg 105: 919-927 (2000) SIRG (00)46

Objective To compare potential risk factors for future ill health in women with implants with other women receiving plastic surgery

Methods Retrospective study, using telephone interviews covering a number of health and health related areas

Results A number of differences emerged in relation to the implanted women. They were more likely to have been exposed to exogenous hormones, have more self-reported ill health and have other socio-demographic differences

IRG Comment A poor study addressing a question of little relevance, retrospectively conducted, which introduces recall bias, with little information on subject selection, producing results that might be expected. Does not contribute to literature.

This paper established an epidemilogical baseline for breast implant patients compared with those undergoing other types of plastic surgery. Some of the differences are interesting but their biological significance is not clear. The one that is worth separating out for special mention is the apparent increase in a family history of rheumatoid arthritis. This observation merits further study.

Kalick S M; Discussion: Characteristics Of A Population Of Women With Breast Implants Compared With Women Seeking Other Types Of Plastic Surgery. Plast-Reconstr-Surg 105: 928-929 (2000) SIRG (00)47

IRG Comment Commentary on paper by Brinton et al., which reaches similar negative conclusions about the scientific value of paper to those of the IRG. This  commentary adds nothing new.

Rohrich R J, Kenkel J M, Adams W P, Beran S & Conner W C H; A Prospective Analysis Of Patients Undergoing Silicone Breast Implant Explantation. Plast-Reconstr-Surg 105: 2529-2537 (2000)SIRG (00)49

Objective To determine the effects on ill-health of explatation on women who requested an operation because of fears about possible adverse health effects

Methods Prospective study at baseline, 6 weeks and 6 months, comparing 38 implanted women with a similar number of population controls

Results Implanted women had more self reported ill health, musculo –skeletal symptoms and other symptoms at baseline, which were more likely to improve after explantation than background change in control women

IRG Comment Another truly appalling study, with an inappropriate comparison group and reaching the foregone conclusion that women who are anxious about their implants will have more health concerns, which are likely to improve after explanation

Young V L, Atagi T A & Watson M E; Discussion: A Prospective Analysis Of Patients Undergoing Silicone Breast Implant Explantation. Plast-Reconstr-Surg 105: 2540-2543 (2000) [SIRG (00)50]

IRG Comment Commentary on the paper by Rohrich et al., which reaches similar critical conclusions to those of the IRG..

Peters W,; Discussion: A Prospective Analysis Of Patients Undergoing Silicone Breast Implant Explantation. Plast-Reconstr-Surg 105: 2540-2543 (2000) [SIRG (00)51]

IRG Comment Commentry on the paper by Rohrich et al.,, ignoring methodological weaknesses, but it does highlight the paucity of good prospective data and that the objective of the Rohrich study was laudable

Beekman W H, Hage J J, Taets Van Amerongen A H M & Mulder J W; Accuracy Of Ultrasonography And Magnetic Resonance Imaging In Detecting Failure Of Breast Implants Filled With Silicone Gel. Scand J Plast Reconstr Hand Surg 33: 415-418 (1999) [SIRG (00)57]

This paper claims that MRI is the gold standard for imaging possible implant ruptures with ultrasound less accurate. It is a very small series analysing 35 silicone gel implants in 18 patients. MRI missed 2 ruptures out of 16 but didn’t incorrectly diagnose any implants as ruptured which were intact out of 16. All ruptures were intracapsular.

Collis N & Sharpe D T; Silicone Gel-Filled Breast Implant Integrity: A Retrospective Review Of 478 Consecutively Explanted Implants. Plast-Reconstr-Surg 105: 1979-1985 (2000) [SIRG (00)58]
478 implants were removed over 11 years. The following factors were associated with an increased likelihood of rupture.

1. Second generation thin wall implants (inserted in the later 70’s and early 80’s).
2. Subpectoral position of implant.

Capsular contracture was not related to increased chance of implant rupture.

Young V L, Brandon H J & Watson M E; Discussion: Silicone Gel-Filled Breast Implant Integrity: A Retrospective Review Of 478 Consecutively Explanted Implants. Plast-Reconstr-Surg 105: 1986-1989 (2000) [SIRG (00)59]
This is a discussion of the paper by Collis et al and makes the following points:

1. The findings that the subpectoral pocket was associated with an increased likelihood of rupture and that presence of capsule was not associated with increased chance of rupture contrasts with Feng & Amini’s paper which shows the opposite so this needs further investigation.
2. Dr Young is unhappy with classing of implants into different generations based on the year of implantation as different types of implants were introduced in difference countries in different years and many implants stay on the shelf for some years before they are implanted thus blurring the divisions between one generation and another.
3. They recommend a prospective study on the life of implants but don’t recommend this is done in the USA as the population is too mobile.

Dalal Milind, Cooper M & Munnoch D A; Coagulated Blood Within A Replaced Intact Silicone Gel Breast Implant. Plast-Reconstr-Surg 105: 2270-2271 (2000) SIRG (00)60
This is a case report where coagulated blood was found within an apparently intact implant. Their explanation is that a microscopic hole allowed the less viscous blood to enter the implant but did not allow the more viscous silicone get to migrate out of it.

Vandeweyer E & Deraemaecker R; Radiation Therapy After Immediate Breast Reconstruction With Implants. Plast-Reconstr-Surg 106: 56-58 (2000) [SIRG (00)61]
An increased incidence of fibrous capsule contracture is reported if radiotherapy is given following an implant reconstruction after masectomy. The authors recommend therefore that, if x-ray therapy is likely to be required after a masectomy, it is not a good idea to carry out an immediate reconstruction with an implant but to do the implantation after the radiotherapy.

They found that 100% of patients irradiated after implantation developed a Baker Grade III of IV capsule contracture compared to 3.4% of patients developing a Grade III or IV when radiotherapy wasn’t used.

Young V L; Discussion: Radiation Therapy After Immediate Breast Reconstruction With Implants. Plast-Reconstr-Surg 106: 59-60 (2000) [SIRG (00)62]
Discussion of Vandeweyer’s paper - Dr Young agreed with the findings in the paper but pointed out that reconstruction not using silicone implants was not affected adversely by post-operative radiotherapy.

Godwin Y; Do They Listen? A Review Of Information Retained By Patients Following Consent For Reduction Mammoplasty. British Journal Of Plastic Surgery 53: 121-125 (2000) [SIRG (00)56]
A well written paper that goes to show that if consent is properly sought, the patients are satisfied. It also confirms the well known fact that retention of information is poor when transmitted verbally.

There is a brief comment about the provision of fact sheets. The value of these should be emphasised.

Deapen D, Hamilton A, Bernstein L & Brody G S; Breast Cancer Stage At Diagnosis And Survival Among Patients With Prior Breast Implants. Plast-Reconstr-Surg 105: 535-540 (2000) [SIRG (00)55]
A small sample size which supports other reports that there is no evidence that breast implants alter either the detection time or survival rates of patients suffering from breast cancer.

Immunology
Oliver DW, Walker MS, Walters AE, et al. Anti-silicone antibodies and silicone containing breast implants. Br J Plast Surg (2000) 53, 41-414 [SIRG (00)65]
In this study from the Department of Plastic and Reconstructive Surgery, Addenbrooke’s Hospital, Cambridge, sera of women receiving SBI were tested for the presence of antibodies that reacted with silicone polymers in an enzyme linked immunosorbent assay (ELISA). There were 20 women with SBI in the group, randomly selected from patients attending the department. Their median age was 42 years; implants came from several different manufacturers; the time after implantation when serum samples were taken varied from 6 weeks to 20 years. Three control groups were used for comparison. The first consisted of 20 women within the same age range but without SBI, who either were members of the nursing staff or were patients undergoing surgical breast reductions. The second control group numbered 20 women with established autoimmune disease, and raised levels of either rheumatoid factor or anti-nuclear antibody. The last control group was one of 20 randomly selected blood donors (both sexes). Unlike the samples of all other groups, the sera from the blood donors had been stored for many months.

The ELISA technique is a conventional one, and quantitative assessment was made by comparisons against a set of standards prepared by diluting a pool of high titre IgG containing sera. Briefly, microwells were first coated with dimethyl siloxane. To these were added the test samples of serum, diluted 1:50; test wells and sera were incubated for 30 minutes at room temperature, washed (x3), then treated with peroxidase conjugated anti-human IgG and followed by a similar incubation period. Finally, the wells were washed again (x4) and the amount of absorbed anti-human IgG estimated using standard colorimetric methods.

Results:
There was no significant difference in the levels of silicone-reactive IgG in sera from the women with SBI and the first control group. The other two control groups (women with autoimmune disease, and the blood donors) both had significantly higher levels of silicone-reactive IgG than the group of SBI recipients.

IRG comment:
A careful study showing that women with SBI do NOT have raised levels of silicone-reactive IgG. The term anti-silicone antibodies is not used here because there is no unambiguous evidence that silicone is immunogenic and can induce immunologically specific antibodies. The authors draw attention to the possibility that anomalous results may be due to storage of serum samples. The likelihood is that IgG aggregates formed during storage bind non-specifically to silicone.

Dalu A, Blaydes BS, Lomax LG, et al. A comparison of the inflammatory response to polydimethylsiloxane (PDMS) implant in male and female Balb/c mice. Biomaterials (2000) 21, 1947-1957 [SIRG (00)69]
Five groups (n=6) of male Balb/c mice, and a similar number of female mice, received two subcutaneous implants of smooth pieces of PDMS. Equal numbers of control mice were subjected to the same surgical procedures but were not implanted with PDMS. The implants and surrounding tissue were resected at 2, 14, 42, 70 or 105 days after implantation, and assessed by a pathologist for the numbers of inflammatory cells present, and the presence or absence of a capsule. In addition, immunohistology was used to assess the amount of TNF-alpha and IL-1beta present. All histological assessments were carried out with the pathologist being unaware of the sex or treatment of the relevant mice, or the time of the sampling of the specimen.

Results:
The resulting inflammatory response was detected at 2 days in both male and female experimental and control mice. However in controls, the response resolved completely within 14-42 days. In the experimental mice, maximum responses were observed at 14 days and persisted (mild to moderate) for the duration of the experiment. Except for a slightly greater inflammatory response at 2 days in the group of male mice compared the corresponding group of female mice, no significant differences between the response in the two sexes were observed.

Immunostaining for TNF-alpha and IL-1beta followed the same general pattern, in that all groups of mice showed some cytokine secretion at 2 days, but in the control groups this never rose above grade 2 (mild staining) at any time during the experiment. In the experimental mice, peak staining intensity for both TNF and IL-1 was seen at 14 days, after which it fell. However at many time points, cytokine staining intensity was significantly greater than that seen in the controls. Further peak staining intensity was greatest in the implanted female mice.

IRG comments:
The report is consistent with the many studies that have demonstrated an inflammatory response to silicone implants. It also documents differences between the sexes in their inflammatory responses, which is in keeping with known differences in immune responses.

O’Hanlon TP, Lawless OJ, Katzin WE, et al. Restricted and shared patterns of TCR p-chain gene expression in SBI capsules and remote sites of tissue inflamation. J Autoimmun (2000) 14,283-293. [SIRG (00)68]
The purpose of this study was to identify the variable p-chain gene families expressed by T lymphocytes infiltrating the capsules of SBI and remote inflammatory tissues. If the T cells infiltrating the capsules were derived from entirely heterogeneous clonotypes, it might imply that the infiltrating T cells were a secondary, bystander component of the infiltrate; however, if the analysis indicated restricted clonality of the T cells, the findings would be consistent with an hypothesis of an antigen-driven T cell response.

Tissue and blood samples were collected from 3 patients, all of whom had received SBI that were later explanted. The first patient had been diagnosed with rheumatoid arthritis before SBI implantation; the second patient had an atypical connective tissue disease diagnosed after implantation; the third developed an undifferentiated connective tissue disease with systemic vasculitis, and a monoclonal gammopathy.

Total DNA was isolated from SBI capsules, lymph node, muscle, or skin biopsy. This was reverse transcribed, and the cDNA product used for individual PCR amplifications with one of 23 primers for different variable p-chain gene families. The products of amplification were size-fractionated and extracted from the polyacrylamide gels, re-amplified and ultimately ligated into a plasmid which was used to transform bacterial cells. Plasmid DNA from recombinants was then sequenced.

Results:
Overall, the number of variable p-chain gene families detected varied considerably among tissue and patients. However, in some cases, identical T cell clones were found at sites of capsular and remote sites of inflammation. The most dramatic example was found in patient 1, where a unique BV3 T cell receptor clone was detected in both left and right SBI capsules, skeletal muscle, and a remote vasculitic skin lesion.

The authors note in the discussion that an antigen responsible for initiating and/or promoting chronic inflammation in SBI capsules has not been found. They mention the possibility of a self protein adsorbed to the SBI that might be immunogenic. They acknowledge that in patients with established disease, it is not possible to determine how the restricted T cell clonotypes arose.

IRG comment:
The hypothesis that prompted this study is a reasonable one, but in order to obtain data that allows one to reach a firm conclusion, it would be necessary to study many more patients, and in particular, patients with SBI but without autoimmune disease. This study does not allow one to draw firm conclusions.

Naim JO, Satoh M, Buehner NA, et al. Induction of hypergammagolbulinemia and macrophage activation by silicone gels and oils in female A.SW mice. Clin & Diag Lab, Immunol (2000) 7,366-370 [SIRG (00)67]
SW mice were intraperitoneally injected with one of the following:- silicone gel, silicone oil, pristane, or buffered saline. Blood samples were taken intermittently for 6 months. No significant differences in lupus-associated autoantibody levels were found between the saline injected control mice and the groups that received silicone gel or oil. Pristante injected mice, as expected, showed significant titres of these antibodies. Silicone gel or oil injected mice showed significant rises in IgM levels, which persisted for a prolonged period, and also IgG1 levels.

Peritoneal macrophages were pooled from mice given the same treatment, and cultures set up with LPS. After incubation of cultures for 16 hours at 37C, supernatant fluids were removed and their content of IL-6 and IL-1 beta measured using a commercial ELISA kit. It was observed that macrophage/LPS cultures from pristane-, silicone gel-, and silicone oil-treated mice produced greater amounts of IL-6 than cultures from saline injected mice. The increase was dose dependent.

Cultures from all groups of mice produced IL-1B. In cultures from mice given silicone oil, silicone gel or pristane, the higher doses (5 or 25 ng/ml) of LPS appeared to stimulate higher levels of IL-1B; however the experiment was not designed to demonstrate the statistical significance of any differences observed.

It was concluded that the increase of IgM and IgG1, and the overproduction of IL-6 and IL-1B may be relevant to the symptoms occurring in certain individuals with silicone implants. However, further experimental and clinical studies would be necessary to address this question.

IRG comments:
The authors’ conclusion is valid, but with the caveat that their finding of increased IL-1B by macrophage/LPS cultures from the silicone treated mice remain to be checked for statistical significance.