- Email: [email protected]
Silicone gel-filled testicular prosthesis and systemic disease
SILICONE
GEL-FILLED TESTICULAR PROSTHESIS AND SYSTEMIC DISEASE RICHARD PIDUTTI, M.D. ALVARO MORALES, M.D. From the Department of Urology, Queen’s University, Kingston, Ontario, Canada
ABSTRACT-Concerns exist regarding a possible link between the presence of silicone implants and the development of systemic disease. A retrospective review was carried out to determine whether or not a pattern of diseases could be found after the implantation of a testicular prosthesis. A specific pattern of diseases did not emerge in a group of 34 men harboring a scrotal silicone gel implant for a mean period of over five years. The findings, with a limited population and period of follow-up, are not conclusive but provide basis for reassurance to men about the health implications of their implants.
Silicone implants for a variety of human uses have been available for over three decades. This material gained an enormous popularity in cosmetic surgery as a breast prosthesis, of which it is estimated that close to 2 million have been used.’ Despite this vast experience, the safety of silicone in humans remains unknown.2 Very serious concerns have been raised recently about the possible association of the presence of silicone in the body and the development of neoplasia, connective tissue diseases, and autoimmune disorders.3-5 Although breast implants are the ones that achieved popular notoriety, some testicular prostheses share the same physical and chemical characteristics but have received little attention as potential etiologic agents of similar conditions associated with the larger mammary implants. The American Urological Association has indicated that silicone-based testicular prostheses should not be used,6 and the largest manufacturer of the devices has suspended production and distribution of the product.7 In our Department the situation was considered carefully as an issue of patient care as well as quality assurance. It was further decided that, in view of the widespread concerns, patients wearing such scrotal implants should be advised on the basis of a review of our experience. The unique characteristics of medical care in Kingston, Ontario, are fa-
Submitted: March 24, 1993, accepted
(with revisions): April 26,
1993
UROLOGY
I A~GLTT1993 I VOLUME42. NUMBER 2
vorable for this. type of study because all secondary and tertiary care for the region is provided by two hospitals and only by physicians with university appointments. This results in not only a central source for medical attention of most serious illness in the area but also permits ready accessibility to the records. We have conducted a retrospective study in a search for any possible association between silicone scrotal implants and the development of any local or systemic disease that might suggest a causal effect from chemical leaching. MATERIAL AND METHODS A chart analysis of all patients receiving testicular prostheses at Queen’s University teaching hospitals (Kingston General Hospital and Hotel Dieu Hospital) from 1978 until 1991 was performed. Particular attention was given to the health problems encountered by the patients after the date of implantation. The patients’ records were researched at both hospitals for inpatient, emergency, and outpatient visits. All testicular prostheses used at our Center during this period were the Silastic Gel-Filled Testicular Implant (Dow Corning, Arlington, TN). The basic chemical structure, polydimethylsiloxane, has remained unchanged since the product was introduced in 1972. However, some minor modifications have been made since then: in 1976 the gel was made more responsive by increasing the polydimethylsiloxane crosslinks, in 1979 by adding a new anchoring loop, and in 1988 a slightly firmer gel was employed.7
155
TABLE I.
Indications for implantation of prosthesis
Indications
No. of Pts.
Anorchia Post orchidectomy for Prostate cancer Testicular torsion Testicular mass Orchitis Post surgical atrophy (iatrogenic) Total
21 11* 7t 6 4 2 51
*Implant removedbecause ojinjection in 2 patients. in 1 patient. tImplant removedbecauseofinjection
TABLE II.
Diagnoses made after implantation
Diagnosis
No. of Pts.
Orthopedic
injuries
11
Miscellaneous
injuries
3*
Osteoarthritis
of hips
1
esophagitis
1
Ulcerative Alcoholism
with gastritis
Sarcoidosis
and hepatitis
1 (I.V. drug abuser)
Dementia
1
Mild chronic obstructive
pulmonary
disease
lnguinal hernia
A total of 51 patients received 63 testicular prostheses between 1978 and 1991 at Queen’s University teaching hospitals. The indications for implantation are listed in Table I. Implants for cosmetic reasons are not used routinely but are considered at the patient’s request. Three patients had the prostheses removed within two months of implantation due to infection; these patients were excluded from the study. In addition, 14 patients were lost to follow-up within six months of the implant surgery, after their initial postoperative visit. They are also excluded from further analysis. Therefore, 34 patients were available for evaluation. RESULTS The mean follow-up period for these 34 patients was 5.04 years. Their average age is thirty-nine years (range 4-82). Table II lists the diagnoses encountered in these men after implantation of the silicone prostheses. A wide variety of diagnoses are represented; however, no diagnosis/category of diagnoses appears more than once except for orthopedic injuries. These injuries were found to involve different areas of the skeleton and are not believed to have any common etiology. COMMENT Concern over the safety of silicone gel prostheses has centered on breast implants over the past several years. The silicone gel is composed of polydimethylsiloxane subunits4 and is the same in breast and testicular prostheses.’ The greatest risk of silicone implants is posed by gel penetration or “bleed” out through the intact or ruptured capsule.s Estimates for rates of rupture of breast implants range from 4-6 percent.2 The figures for testicular implants are not known. The outer shells of breast and testicular implants are made from an elastomer of polydimethylsiloxane with amorphous silica added and
156
1 1 1
Learning disability
1
Cholelithiasis
1
Calf and axillary vein thrombosis
1
Urolithiasis
1
Recurrent
(Ca oxalate) UTls
1
Urethritis
1
Problems
related to surgery
lnguinal pain
I
Hot flashes
1
*Fracturednose (I), head
injury (11, and foreign body in left eye.
were identical until 1983 when the shell of the former was laminated with a barrier coat of fluorosilicone.’ This coating that sharply reduces gel diffusion or “bleed” is not present in the shell of the testicular prosthesis. Approximately 100,000 silicone testicular prostheses have been sold by Dow Coming in North America since production began in 1972.’ Dow Corning captured 60 percent of the market in the U.S.A. while four other manufacturers held the remainder of market share: Mentor (Norwell, Massachusetts) , Surgitek (Brantford, Ontario, Canada), McGhan (Santa Barbara, California), Cox-Uphoff (Carpinteria, California) .’ There is a paucity of scientific data implicating silicone implants in the development of disease.* The case against them appears to be little more than anecdotal reports and speculation. The major areas of concern expressed by the opponents of silicone implants are (1) possible association with carcinogenesis,3 (2) generalized connective tissue diseases,4 and (3) autoimmune disorders.5 The risk of carcinogenesis is always a concern with exposure to foreign substances, particularly synthetic material. No studies to date have shown a convincing causative link between silicone and human cancers.s Two studies specifically investigating the risk of breast cancer in the presence of
UROLOGY
I AUGUST1993 / VOLUME42, NUMBER2
breast implants failed to find a relationship of implants to this neoplasm.9J0 Antibodies to silicone protein complexes were reported by Heggers. 5 The presence of these antibodies, however, has not been correlated with rheumatic disease.l’ The American College of Rheumatology has issued a statement on the subject of connective tissue diseases indicating that “there is no convincing evidence that these implants cause any generalized disease.“‘* Penile prostheses and genitourinary sphincters are widely used in urologic practice. In a careful study of patients undergoing removal or replacement of these devices, Barrett et ~1.‘~ found silicone particles in the periprosthetic fibrous tissue as well as in the draining lymph nodes of most of these patients. However, in none of the 26 patients in the study was there any evidence of adjuvant disease occurring after implantation. The authors correctly concluded that “long-term (20 years or more) assessment” will be required to determine conclusively the risk posed by these devices. Silicone is ubiquitously employed in North America. It is used in the elaboration of foodstuffs, cosmetics, and many medical instruments such as syringes. Exposure to this material is almost universal in developed countries. It is estimated that many patients receiving regular injections, such as diabetics, would receive a higher exposure to silicone from material released from the syringes (where it is used as a lubricant) than from an implant. 8 It would be of interest to the urologic community to determine whether or not adverse effects are present in impotent men using intracavernosal injections in which silicone would, for all intents and purposes, gain entrance by the intravenous route into the systemic circulation. We fully recognized the limitations of a retrospective study, with a limited population and short follow-up as a source for determining whether or not intra-scrotal silicone prostheses are a causal agent of a variety of physical disorders. We do not believe that these findings can be considered conclusive or universally applicable to all men who had received a testicular prosthesis. Nevertheless, the results of our study have not suggested an association between the implants and the development of any disease. We feel comfortable in advising our patients that the material in their scrotum is safe and that removal of the
UROLOGY
! AIJGCJST 1993 / VOLUME42, NUMBER2
device is not warranted, a view in agreement with the position of the American Urological Association.6 In addition, we view the insertion of these prostheses as an integral part of the treatment of the underlying disease and believe, therefore, that they should not fall under the same restrictions applied to cosmetic implants. The implications of a causative role of silicones in the development of disease are profound in view of the widespread use of these compounds. Singling out silicone implants may be inappropriate in this respect. Despite the results of this study, further retrospective assessments with larger number of men and longer follow-up would be more reassuring about the safety of these implants and the need for their removal. Alvaro
Morales,
M.D.
Department of Urology, Queen’s University Kingston General Hospital Kingston, Ontario K7L 2V7 REFERENCES 1. Angel1 M: Breast implants, protection or paternalism? N Engl J Med 326: 1695-1696,1992. 2. Kessler DA: The basis of the FD& decision on breast implants. N Engl J Med 326: 1713-1715,1992. 3. Wolfe S: Testimony given at FDA hearing, February 19, 1992, Rockville, MD, Food and Drug Administration, 1992. 4. van Nunen SA, Gatenby PA, and Basten A: Postmammaplasty connective tissue disease. Arthritis Rheum 25: 694-697,1982. 5. Heggers JP: Immunology of silicone, presented at Toxicology Forum, Washington, DC, February 16, 1992. 6. American Urological Association: Position statement on implants, AUA Today 5: 11, 1992. 7. Curtis J (Dow Coming): Personal communication, December, 1992. 8. Fisher JC: The silicone controversy, when will science prevail? N Engl J Med 326: 1696-1698, 1992. 9. Deapen DM, Pike MC, Casagrande JT, and Brody GS: The relationship between breast cancer and augmentation mammaplasty: an epidemiological study. Plast Reconstr Surg 77: 361-367,1986. 10. Berkel H, Birdsell DC, and Jenkins H: Breast augmentation: a risk factor for breast cancer? N Engl J Med 326: 1649-1653,1992. 11. Weisman MH, Vechionne TR, Albert D, Moore TL, and Mueller MR: Connective tissue disease following breast augmentation: a preliminary test of the human adjuvant disease hypothesis. Plast Reconstr Surg 82: 626-630, 1988. 12. Sargent JS: Silicone gel breast implants and rheumatic disease, hotline. Newslett Am Co11 Rheumatol, February 27, 1992. 13. Barrett DM, O’Sullivan DC, Malizia AA, Reiman HM, and Abell-Aleff PC: Particle shedding and migration from silicone genitourinary prosthetic devices. J Urol 146: 319-322, 1991.
157
GEL-FILLED TESTICULAR PROSTHESIS AND SYSTEMIC DISEASE RICHARD PIDUTTI, M.D. ALVARO MORALES, M.D. From the Department of Urology, Queen’s University, Kingston, Ontario, Canada
ABSTRACT-Concerns exist regarding a possible link between the presence of silicone implants and the development of systemic disease. A retrospective review was carried out to determine whether or not a pattern of diseases could be found after the implantation of a testicular prosthesis. A specific pattern of diseases did not emerge in a group of 34 men harboring a scrotal silicone gel implant for a mean period of over five years. The findings, with a limited population and period of follow-up, are not conclusive but provide basis for reassurance to men about the health implications of their implants.
Silicone implants for a variety of human uses have been available for over three decades. This material gained an enormous popularity in cosmetic surgery as a breast prosthesis, of which it is estimated that close to 2 million have been used.’ Despite this vast experience, the safety of silicone in humans remains unknown.2 Very serious concerns have been raised recently about the possible association of the presence of silicone in the body and the development of neoplasia, connective tissue diseases, and autoimmune disorders.3-5 Although breast implants are the ones that achieved popular notoriety, some testicular prostheses share the same physical and chemical characteristics but have received little attention as potential etiologic agents of similar conditions associated with the larger mammary implants. The American Urological Association has indicated that silicone-based testicular prostheses should not be used,6 and the largest manufacturer of the devices has suspended production and distribution of the product.7 In our Department the situation was considered carefully as an issue of patient care as well as quality assurance. It was further decided that, in view of the widespread concerns, patients wearing such scrotal implants should be advised on the basis of a review of our experience. The unique characteristics of medical care in Kingston, Ontario, are fa-
Submitted: March 24, 1993, accepted
(with revisions): April 26,
1993
UROLOGY
I A~GLTT1993 I VOLUME42. NUMBER 2
vorable for this. type of study because all secondary and tertiary care for the region is provided by two hospitals and only by physicians with university appointments. This results in not only a central source for medical attention of most serious illness in the area but also permits ready accessibility to the records. We have conducted a retrospective study in a search for any possible association between silicone scrotal implants and the development of any local or systemic disease that might suggest a causal effect from chemical leaching. MATERIAL AND METHODS A chart analysis of all patients receiving testicular prostheses at Queen’s University teaching hospitals (Kingston General Hospital and Hotel Dieu Hospital) from 1978 until 1991 was performed. Particular attention was given to the health problems encountered by the patients after the date of implantation. The patients’ records were researched at both hospitals for inpatient, emergency, and outpatient visits. All testicular prostheses used at our Center during this period were the Silastic Gel-Filled Testicular Implant (Dow Corning, Arlington, TN). The basic chemical structure, polydimethylsiloxane, has remained unchanged since the product was introduced in 1972. However, some minor modifications have been made since then: in 1976 the gel was made more responsive by increasing the polydimethylsiloxane crosslinks, in 1979 by adding a new anchoring loop, and in 1988 a slightly firmer gel was employed.7
155
TABLE I.
Indications for implantation of prosthesis
Indications
No. of Pts.
Anorchia Post orchidectomy for Prostate cancer Testicular torsion Testicular mass Orchitis Post surgical atrophy (iatrogenic) Total
21 11* 7t 6 4 2 51
*Implant removedbecause ojinjection in 2 patients. in 1 patient. tImplant removedbecauseofinjection
TABLE II.
Diagnoses made after implantation
Diagnosis
No. of Pts.
Orthopedic
injuries
11
Miscellaneous
injuries
3*
Osteoarthritis
of hips
1
esophagitis
1
Ulcerative Alcoholism
with gastritis
Sarcoidosis
and hepatitis
1 (I.V. drug abuser)
Dementia
1
Mild chronic obstructive
pulmonary
disease
lnguinal hernia
A total of 51 patients received 63 testicular prostheses between 1978 and 1991 at Queen’s University teaching hospitals. The indications for implantation are listed in Table I. Implants for cosmetic reasons are not used routinely but are considered at the patient’s request. Three patients had the prostheses removed within two months of implantation due to infection; these patients were excluded from the study. In addition, 14 patients were lost to follow-up within six months of the implant surgery, after their initial postoperative visit. They are also excluded from further analysis. Therefore, 34 patients were available for evaluation. RESULTS The mean follow-up period for these 34 patients was 5.04 years. Their average age is thirty-nine years (range 4-82). Table II lists the diagnoses encountered in these men after implantation of the silicone prostheses. A wide variety of diagnoses are represented; however, no diagnosis/category of diagnoses appears more than once except for orthopedic injuries. These injuries were found to involve different areas of the skeleton and are not believed to have any common etiology. COMMENT Concern over the safety of silicone gel prostheses has centered on breast implants over the past several years. The silicone gel is composed of polydimethylsiloxane subunits4 and is the same in breast and testicular prostheses.’ The greatest risk of silicone implants is posed by gel penetration or “bleed” out through the intact or ruptured capsule.s Estimates for rates of rupture of breast implants range from 4-6 percent.2 The figures for testicular implants are not known. The outer shells of breast and testicular implants are made from an elastomer of polydimethylsiloxane with amorphous silica added and
156
1 1 1
Learning disability
1
Cholelithiasis
1
Calf and axillary vein thrombosis
1
Urolithiasis
1
Recurrent
(Ca oxalate) UTls
1
Urethritis
1
Problems
related to surgery
lnguinal pain
I
Hot flashes
1
*Fracturednose (I), head
injury (11, and foreign body in left eye.
were identical until 1983 when the shell of the former was laminated with a barrier coat of fluorosilicone.’ This coating that sharply reduces gel diffusion or “bleed” is not present in the shell of the testicular prosthesis. Approximately 100,000 silicone testicular prostheses have been sold by Dow Coming in North America since production began in 1972.’ Dow Corning captured 60 percent of the market in the U.S.A. while four other manufacturers held the remainder of market share: Mentor (Norwell, Massachusetts) , Surgitek (Brantford, Ontario, Canada), McGhan (Santa Barbara, California), Cox-Uphoff (Carpinteria, California) .’ There is a paucity of scientific data implicating silicone implants in the development of disease.* The case against them appears to be little more than anecdotal reports and speculation. The major areas of concern expressed by the opponents of silicone implants are (1) possible association with carcinogenesis,3 (2) generalized connective tissue diseases,4 and (3) autoimmune disorders.5 The risk of carcinogenesis is always a concern with exposure to foreign substances, particularly synthetic material. No studies to date have shown a convincing causative link between silicone and human cancers.s Two studies specifically investigating the risk of breast cancer in the presence of
UROLOGY
I AUGUST1993 / VOLUME42, NUMBER2
breast implants failed to find a relationship of implants to this neoplasm.9J0 Antibodies to silicone protein complexes were reported by Heggers. 5 The presence of these antibodies, however, has not been correlated with rheumatic disease.l’ The American College of Rheumatology has issued a statement on the subject of connective tissue diseases indicating that “there is no convincing evidence that these implants cause any generalized disease.“‘* Penile prostheses and genitourinary sphincters are widely used in urologic practice. In a careful study of patients undergoing removal or replacement of these devices, Barrett et ~1.‘~ found silicone particles in the periprosthetic fibrous tissue as well as in the draining lymph nodes of most of these patients. However, in none of the 26 patients in the study was there any evidence of adjuvant disease occurring after implantation. The authors correctly concluded that “long-term (20 years or more) assessment” will be required to determine conclusively the risk posed by these devices. Silicone is ubiquitously employed in North America. It is used in the elaboration of foodstuffs, cosmetics, and many medical instruments such as syringes. Exposure to this material is almost universal in developed countries. It is estimated that many patients receiving regular injections, such as diabetics, would receive a higher exposure to silicone from material released from the syringes (where it is used as a lubricant) than from an implant. 8 It would be of interest to the urologic community to determine whether or not adverse effects are present in impotent men using intracavernosal injections in which silicone would, for all intents and purposes, gain entrance by the intravenous route into the systemic circulation. We fully recognized the limitations of a retrospective study, with a limited population and short follow-up as a source for determining whether or not intra-scrotal silicone prostheses are a causal agent of a variety of physical disorders. We do not believe that these findings can be considered conclusive or universally applicable to all men who had received a testicular prosthesis. Nevertheless, the results of our study have not suggested an association between the implants and the development of any disease. We feel comfortable in advising our patients that the material in their scrotum is safe and that removal of the
UROLOGY
! AIJGCJST 1993 / VOLUME42, NUMBER2
device is not warranted, a view in agreement with the position of the American Urological Association.6 In addition, we view the insertion of these prostheses as an integral part of the treatment of the underlying disease and believe, therefore, that they should not fall under the same restrictions applied to cosmetic implants. The implications of a causative role of silicones in the development of disease are profound in view of the widespread use of these compounds. Singling out silicone implants may be inappropriate in this respect. Despite the results of this study, further retrospective assessments with larger number of men and longer follow-up would be more reassuring about the safety of these implants and the need for their removal. Alvaro
Morales,
M.D.
Department of Urology, Queen’s University Kingston General Hospital Kingston, Ontario K7L 2V7 REFERENCES 1. Angel1 M: Breast implants, protection or paternalism? N Engl J Med 326: 1695-1696,1992. 2. Kessler DA: The basis of the FD& decision on breast implants. N Engl J Med 326: 1713-1715,1992. 3. Wolfe S: Testimony given at FDA hearing, February 19, 1992, Rockville, MD, Food and Drug Administration, 1992. 4. van Nunen SA, Gatenby PA, and Basten A: Postmammaplasty connective tissue disease. Arthritis Rheum 25: 694-697,1982. 5. Heggers JP: Immunology of silicone, presented at Toxicology Forum, Washington, DC, February 16, 1992. 6. American Urological Association: Position statement on implants, AUA Today 5: 11, 1992. 7. Curtis J (Dow Coming): Personal communication, December, 1992. 8. Fisher JC: The silicone controversy, when will science prevail? N Engl J Med 326: 1696-1698, 1992. 9. Deapen DM, Pike MC, Casagrande JT, and Brody GS: The relationship between breast cancer and augmentation mammaplasty: an epidemiological study. Plast Reconstr Surg 77: 361-367,1986. 10. Berkel H, Birdsell DC, and Jenkins H: Breast augmentation: a risk factor for breast cancer? N Engl J Med 326: 1649-1653,1992. 11. Weisman MH, Vechionne TR, Albert D, Moore TL, and Mueller MR: Connective tissue disease following breast augmentation: a preliminary test of the human adjuvant disease hypothesis. Plast Reconstr Surg 82: 626-630, 1988. 12. Sargent JS: Silicone gel breast implants and rheumatic disease, hotline. Newslett Am Co11 Rheumatol, February 27, 1992. 13. Barrett DM, O’Sullivan DC, Malizia AA, Reiman HM, and Abell-Aleff PC: Particle shedding and migration from silicone genitourinary prosthetic devices. J Urol 146: 319-322, 1991.
157