Professor J.P. Sloane, University of Liverpool 
Dr. A. J.Darby, Robert Jones & Agnes Hunt Orthopaedic Hospital, Oswestry
Professor A.J. Freemont, University of Manchester 
Professor F.D. Lee, University of Glasgow
 
 

 Fifty two 35mm colour transparencies and accompanying legends submitted by Professor Radford Shanklin, University of Tennessee. The transparencies were photomicrographs of histological sections prepared from tissue removed from women who had been implanted with breast prostheses. Most were of tissue in the immediate vicinity of the implant but some were from distant sites.
 
 

 1.    Three copies of all the transparencies and Professor Shanklin's interpretations of them were prepared by the University of Liverpool and sent to Dr. Darby and Professors Freemont and Lee. A meeting was held on Wednesday 5th November 1997 in the University of Manchester Medical School at which each transparency was projected onto a screen and discussed in detail. A table was drawn up in which the reviewers' consensus opinion on each transparency was recorded alongside that of Professor Shanklin (see Table 1). 

2.    A second meeting was held on Wednesday 10th December 1997 in the University of Manchester Medical School at which the interpretation of the transparencies was discussed with Professor Shanklin. This meeting was attended by Dr. Darby, Professors Freemont and Sloane, Professor Sturrock (Chairman of the Independent Review Group). Dr. Susanne Ludgate and Mr. Jeremy Tinkler of the Medical Devices Agency (Secretariat of the Independent Review Group) were also present. This meeting was recorded and a transcript was prepared.

 Professor Lee could not attend either meeting but submitted a summary of his opinion of the transparencies.
 
 

 1.    The photographs show materials with different optical characteristics around implants. These materials appear as white light on dark ground illumination and using crossed polarisers. They are associated with macrophage responses and different patterns of macrophage differentiation. Some of the macrophages contain globular material presumed to be silicone. In some of the illustrations the material is associated with fibrosis and infiltration of lymphocytes and plasma cells. Elsewhere, however, the foreign material is not associated with inflammatory changes and sometimes inflammatory changes occur apparently in the absence of foreign material.

 2.    A synovial-like membrane may develop between the implant and the host.

 3.    Foreign material, identified by its optical characteristics, may be present in regional lymph nodes or rarely at more distant sites. The material is often within macrophages.

 4.    The precise nature of the foreign material cannot be determined with confidence from the submitted photographs. Much of it is likely to be silicone in view of its optical appearance and the composition of the implant. More sophisticated physical and chemical analyses, however, are needed to determine the precise nature of the material and in particular, if other compounds, such as silica, are present in detectable or significant amounts.

 5.    The review group did not agree with Professor Shanklin that there was evidence in the submitted photomicrographs of an immune response to the foreign material. At the meeting on 10th December, it became clear that the reason for this fundamental disagreement was due to a difference in diagnostic criteria. Professor Shanklin was prepared to conclude that simply because lymphocytes were present in the tissues that an immune response was taking place and that it was not even necessary to demonstrate that these cells exhibited molecular evidence of activation. The review group could not support this contention.

 6.    More specifically there was disagreement on the criteria for diagnosing vasculitis said by Professor Shanklin to be present in several of the photographs. The review group, in line with standard practice, insisted that in order to diagnose vasculitis, there should be evidence of inflammation of the blood vessel walls themselves as manifested by one or more of the following changes:

    a) evidence of damage to endothelial cells
   b) the presence of intravascular thrombus
   c) perivascular oedema and/or erythrocyte extravasation
   d) fibrinoid change of the vessel wall

 Professor Shanklin on the other hand, accepted as evidence of vascuiltis, the mere presence of inflammatory cells around blood vessels.
 
 

 The review group agreed with Professor Shanklin that silicone breast implants are associated with macrophage responses to the foreign material, presumed to be silicone, and that other inflammatory cells, particularly lymphocytes and plasma cells, may be present. The review group also agreed that implants may be associated with local fibrosis and the formation of a synovial-like membrane between the implant and the host. The foreign material may occasionally be seen in sites other than the breast, particularly regional lymph nodes. The review group did not agree, however, that Professor Shanklin had provided evidence that any of the illustrated changes constituted an immune response and in particular that there was any evidence of vasculitis.

 Table 1: Review of 35mm photographs and accompanying legends submitted by Professor Shanklin