- Email: [email protected]
Heterotopic Bone Formation in the Corpus Cavernosum: A Complication of Papaverine-Induced Priapism
0022-534 7 /89/1425-1323$02.00/0 THE JOURNAL OF UROLOGY
142, November
Copyright© 1989 by AMERICAN UROLOGICAL ASSOCIATION, INC.
Printed in U.S.A.
HETEROTOPIC BONE FORMATION IN THE CORPUS CAVERNOSUM: A COMPLICATION OF PAPAVERINE-INDUCED PRIAPISiv1 JONATHAN VAPNEK AND TOM F. LUE From the Department of Urology, University of California School of Medicine, San Francisco, California
ABSTRACT
Priapism is a recognized complication of intracavernous self-injection of vasoactive agents for the management of impotence. We report a case of heterotopic bone formation in the corpus cave:mosum of a patient with papaverine-induced priapisrn. (J. Ural., 142: 1323-1324, 1989) Intracavemous self-injection of vasoactive agents is a well accepted therapy for the management of male erectile dysfunction. Papaverine alone and with phentolamine combinations has been used successfully. Although generally safe, several complications have been reported, including the development of superficial hematoma at the injection site, fibrotic lesions of the tunica albuginea and priapism. We report a case of heterotopic bone formation in the corpus cavernosum of a patient with papaverine-induced priapism. CASE REPORT
A 69-year-old man was referred to us for evaluation of impotence after an episode of papaverine-induced priapism 9 months previously. The priapism resulted from a total dose of 90 mg. and lasted 72 hours when a Winter shunt was performed with a Tru-Cut* needle. Since that time, he had been completely impotent. Medical history was unremarkable and physical examination was remarkable only for induration of the distal corpora cavernosa. Duplex ultrasound penile blood flow study revealed minimal flow through the right cavernous artery and none at all on the left side, as well as increased echogenicity of the corpora cavernosa diffusely during the flaccid state, consistent with interstitial fibrosis. In addition, a 1.5 x 0.5 x 0.5 cm. hyperechoic lesion was noted in the distal corpus (fig. 1). Placement of bilateral semirigid penile prostheses was attempted. After both corporotomies had been made, attempts were made to dilate the corpora with graduated Hegar dilators. While these passed proximally to the level of the crura without difficulty, multiple attempts to pass them distally were unsuccessful. Therefore, the corporotomies were extended distally to the fibrotic, stony-hard areas of the corpora, which could not be incised with a scalpel or dissecting scissors. "\Vith no other obvious choice we then used small orthopedic rongeurs to remove as much of the calcified material as possible. A 9.5 mm. diameter AMS malleable prosthesis then was placed within each corpus and both distal corporotomies were closed with polytetrafluoroethylene (Gore-Tex) patches because of inability to dilate sufficiently. Postoperatively, the patient has done well and has intercourse without difficulty. Pathological examination of the removed corporeal tissue revealed dense fibrous tissue with extensive heterotopic bone formation. Decalcified sections show the characteristic bony trabeculae containing osteocytes (fig. 2).
and prostaglandin El). 1 • 2 Many patients currently are able to have an active sex life with this therapy. While generally safe, complications have been reported. Fibrosis of the corpus cavernosum has been reported on several occasions and generally is associated with long-term, repeated injections. 3- 5 Priapism is another well recognized complication of selfinjection, albeit rare. Cases have been reported that resolve spontaneously as well as those that require surgical intervention.6 The long-term outlook for patients with priapism is poor, with many being permanently impotent. The optimal treatment of such patients is placement of semirigid or malleable prostheses but this invariably is difficult because of the associated fibrosis. 7 • 8 Heterotopic bone formation rarely has been reported in the urological literature. Cases have been reported involving the retroperitoneal tissues 9 • 1° and renal cell carcinoma. 11 Our case involves the corpus cavernosum. Experiments in animals have shown that the urinary transitional epithelium can induce heterotopic ossification in many tissues, although the mechanism remains unclear. 12 Neurogenic factors also have been hypothesized, with circulatory stasis and tissue hypoxia being implicated as etiological factors. In our case heterotopic bone formation resulted from priapism after a single injection of papaverine. Different from simple fibrosis, the pathological specimen showed true bone formation. After exceedingly difficult dissection with orthopedic instruments, we inserted the prostheses and closed the corporotomy with polytetrafluoroethylene patches. We
DISCUSSION
The treatment of male erectile dysfunction has undergone numerous recent developments, including the intracavernous administration of vasoactive agents (papaverine, phentolamine Accepted for publication March 1, 1989. * Travenol Laboratories, Inc., Deerfield, Illinois.
FIG. 1. Transverse 10 MHz. ultrasonogram near tip of corpora cavernosa shows hyperechoic area within corpora. 1323
1324
VAPNEK AND LUE
8. 9. 10. 11. 12.
FIG. 2. Light microscopy of excised penile tissue shows bony trabeculae and osteocytes. Reduced from XlOO.
would reiterate the recommendations of others that a semirigid prosthesis should be used to treat impotence secondary to priapism, since the associated fibrosis and/or bone formation would make an inflatable prosthesis impractical. REFERENCES 1. Gasser, T. C., Roach, R. M., Larsen, E. H., Madsen, P. 0. and Bruskewitz, R. C.: lntracavernous self-injection with phentolamine and papaverine for the treatment of impotence. J. Urol., 137: 678, 1987. 2. Sidi, A. A., Cameron, J. S., Duffy, L. M. and Lange, P. H.: Intracavernous drug-induced erections in the management of male erectile dysfunction: experience with 100 patients. J. Urol., 135: 704, 1986. 3. Larsen, E. H., Gasser, T. C. and Bruskewitz, R. C.: Fibrosis of corpus cavernosum after intracavernous injection of phentolamine/papaverine. J. Urol., 137: 292, 1987. 4. Hu, K.-N., Burks, C. and Christy, W. C.: Fibrosis of tunica albuginea: complication oflong-term intracavernous pharmacological self-injection. J. Urol., 138: 404, 1987. 5. Corriere, J. N., Jr., Fishman, I. J., Benson, G. S. and Carlton, C. E., Jr.: Development of fibrotic penile lesions secondary to the intracorporeal injection ofvasoactive agents. J. Urol., 140: 615, 1988. 6. Halsted, D. S., Weigel, J. W., Noble, M. J. and Mebust, W. K.: Papaverine-induced priapism: 2 case reports. J. Urol., 136: 109, 1986. 7. Bertram, R. A., Carson, C. C., III and Webster, G.D.: Implantation
of penile prostheses in patients impotent after priapism. Urology, 26: 325, 1985. Kela.mi, A.: Implantation of Small-Carrion prosthesis in the treatment of erectile impotence after priapism: difficulties and effects. Urol. Int., 40: 343, 1985. Segen, J. C. and Mahadevia, P.: Heterotopic bone formation occurring near a ligated ureter. J. Urol., 135: 124, 1986. Melekos, M. D., Pantazakos, A., Grekou, A. N., Ghikas, C. and Giannoulis, S.: Formation of heterotopic bone tissue following operation on the renal pelvis. Brit. J. Urol., 61: 458, 1988. Fukuoka, T., Honda, M., Namiki, M., Tada, Y., Matsuda, M. and Sonoda, T.: Renal cell carcinoma with heterotropic bone formation. Urol. Int., 42: 458, 1987. Huggins, C. B.: The formation of bone under the influence of epithelium of the urinary tract. Arch. Surg., 22: 377, 1931. EDITORIAL COMMENT
The treatment of patients with erectile dysfunction by injection of vasoactive agents has become more common in recent years. Priapism or prolonged erection occurs in as many as 15% of the patients, with corporeal fibrosis demonstrated in 2%. As clinical experience with injection of vasoactive agents, especially papaverine and phentolamine, continues additional unique complications will surface. As a result of the recent development of this therapeutic modality, few of these complications have been reported in the literature. While heterotopic bone formation within the corpus cavernosum is not a new observation but has been identified previously as a result of penile trauma, an operation or Peyronie's disease, its relationship to papaverine injection is important for the urological community. As a result of the prolonged priapism and trauma to the distal corpora cavernosa caused by the Winter shunt, which was performed in an effort to eliminate the priapism in this case, the true relationship of papaverine injection to this heterotopic bone formation is not clear. However, there is little question that the priapism resulted from papaverine injection, and the subsequent Winter shunt and corporeal fibrosis were a result of delayed treatment of this complication. Most importantly, while vasoactive injection for the treatment of erectile dysfunction is safe in the majority of patients, complications of this method can be profound and disabling. The urologist who treats patients with pharmacological injection therapy must be diligent, and informed of unique and unusual complications that may occur. Rapid pharmacological treatment for patients with prolonged erection after papaverine injection generally will result in rapid return of the penis to the flaccid state with few complications. Culley C. Carson, III Division of Urology Duke University Medical Center Durham, North Carolina
142, November
Copyright© 1989 by AMERICAN UROLOGICAL ASSOCIATION, INC.
Printed in U.S.A.
HETEROTOPIC BONE FORMATION IN THE CORPUS CAVERNOSUM: A COMPLICATION OF PAPAVERINE-INDUCED PRIAPISiv1 JONATHAN VAPNEK AND TOM F. LUE From the Department of Urology, University of California School of Medicine, San Francisco, California
ABSTRACT
Priapism is a recognized complication of intracavernous self-injection of vasoactive agents for the management of impotence. We report a case of heterotopic bone formation in the corpus cave:mosum of a patient with papaverine-induced priapisrn. (J. Ural., 142: 1323-1324, 1989) Intracavemous self-injection of vasoactive agents is a well accepted therapy for the management of male erectile dysfunction. Papaverine alone and with phentolamine combinations has been used successfully. Although generally safe, several complications have been reported, including the development of superficial hematoma at the injection site, fibrotic lesions of the tunica albuginea and priapism. We report a case of heterotopic bone formation in the corpus cavernosum of a patient with papaverine-induced priapism. CASE REPORT
A 69-year-old man was referred to us for evaluation of impotence after an episode of papaverine-induced priapism 9 months previously. The priapism resulted from a total dose of 90 mg. and lasted 72 hours when a Winter shunt was performed with a Tru-Cut* needle. Since that time, he had been completely impotent. Medical history was unremarkable and physical examination was remarkable only for induration of the distal corpora cavernosa. Duplex ultrasound penile blood flow study revealed minimal flow through the right cavernous artery and none at all on the left side, as well as increased echogenicity of the corpora cavernosa diffusely during the flaccid state, consistent with interstitial fibrosis. In addition, a 1.5 x 0.5 x 0.5 cm. hyperechoic lesion was noted in the distal corpus (fig. 1). Placement of bilateral semirigid penile prostheses was attempted. After both corporotomies had been made, attempts were made to dilate the corpora with graduated Hegar dilators. While these passed proximally to the level of the crura without difficulty, multiple attempts to pass them distally were unsuccessful. Therefore, the corporotomies were extended distally to the fibrotic, stony-hard areas of the corpora, which could not be incised with a scalpel or dissecting scissors. "\Vith no other obvious choice we then used small orthopedic rongeurs to remove as much of the calcified material as possible. A 9.5 mm. diameter AMS malleable prosthesis then was placed within each corpus and both distal corporotomies were closed with polytetrafluoroethylene (Gore-Tex) patches because of inability to dilate sufficiently. Postoperatively, the patient has done well and has intercourse without difficulty. Pathological examination of the removed corporeal tissue revealed dense fibrous tissue with extensive heterotopic bone formation. Decalcified sections show the characteristic bony trabeculae containing osteocytes (fig. 2).
and prostaglandin El). 1 • 2 Many patients currently are able to have an active sex life with this therapy. While generally safe, complications have been reported. Fibrosis of the corpus cavernosum has been reported on several occasions and generally is associated with long-term, repeated injections. 3- 5 Priapism is another well recognized complication of selfinjection, albeit rare. Cases have been reported that resolve spontaneously as well as those that require surgical intervention.6 The long-term outlook for patients with priapism is poor, with many being permanently impotent. The optimal treatment of such patients is placement of semirigid or malleable prostheses but this invariably is difficult because of the associated fibrosis. 7 • 8 Heterotopic bone formation rarely has been reported in the urological literature. Cases have been reported involving the retroperitoneal tissues 9 • 1° and renal cell carcinoma. 11 Our case involves the corpus cavernosum. Experiments in animals have shown that the urinary transitional epithelium can induce heterotopic ossification in many tissues, although the mechanism remains unclear. 12 Neurogenic factors also have been hypothesized, with circulatory stasis and tissue hypoxia being implicated as etiological factors. In our case heterotopic bone formation resulted from priapism after a single injection of papaverine. Different from simple fibrosis, the pathological specimen showed true bone formation. After exceedingly difficult dissection with orthopedic instruments, we inserted the prostheses and closed the corporotomy with polytetrafluoroethylene patches. We
DISCUSSION
The treatment of male erectile dysfunction has undergone numerous recent developments, including the intracavernous administration of vasoactive agents (papaverine, phentolamine Accepted for publication March 1, 1989. * Travenol Laboratories, Inc., Deerfield, Illinois.
FIG. 1. Transverse 10 MHz. ultrasonogram near tip of corpora cavernosa shows hyperechoic area within corpora. 1323
1324
VAPNEK AND LUE
8. 9. 10. 11. 12.
FIG. 2. Light microscopy of excised penile tissue shows bony trabeculae and osteocytes. Reduced from XlOO.
would reiterate the recommendations of others that a semirigid prosthesis should be used to treat impotence secondary to priapism, since the associated fibrosis and/or bone formation would make an inflatable prosthesis impractical. REFERENCES 1. Gasser, T. C., Roach, R. M., Larsen, E. H., Madsen, P. 0. and Bruskewitz, R. C.: lntracavernous self-injection with phentolamine and papaverine for the treatment of impotence. J. Urol., 137: 678, 1987. 2. Sidi, A. A., Cameron, J. S., Duffy, L. M. and Lange, P. H.: Intracavernous drug-induced erections in the management of male erectile dysfunction: experience with 100 patients. J. Urol., 135: 704, 1986. 3. Larsen, E. H., Gasser, T. C. and Bruskewitz, R. C.: Fibrosis of corpus cavernosum after intracavernous injection of phentolamine/papaverine. J. Urol., 137: 292, 1987. 4. Hu, K.-N., Burks, C. and Christy, W. C.: Fibrosis of tunica albuginea: complication oflong-term intracavernous pharmacological self-injection. J. Urol., 138: 404, 1987. 5. Corriere, J. N., Jr., Fishman, I. J., Benson, G. S. and Carlton, C. E., Jr.: Development of fibrotic penile lesions secondary to the intracorporeal injection ofvasoactive agents. J. Urol., 140: 615, 1988. 6. Halsted, D. S., Weigel, J. W., Noble, M. J. and Mebust, W. K.: Papaverine-induced priapism: 2 case reports. J. Urol., 136: 109, 1986. 7. Bertram, R. A., Carson, C. C., III and Webster, G.D.: Implantation
of penile prostheses in patients impotent after priapism. Urology, 26: 325, 1985. Kela.mi, A.: Implantation of Small-Carrion prosthesis in the treatment of erectile impotence after priapism: difficulties and effects. Urol. Int., 40: 343, 1985. Segen, J. C. and Mahadevia, P.: Heterotopic bone formation occurring near a ligated ureter. J. Urol., 135: 124, 1986. Melekos, M. D., Pantazakos, A., Grekou, A. N., Ghikas, C. and Giannoulis, S.: Formation of heterotopic bone tissue following operation on the renal pelvis. Brit. J. Urol., 61: 458, 1988. Fukuoka, T., Honda, M., Namiki, M., Tada, Y., Matsuda, M. and Sonoda, T.: Renal cell carcinoma with heterotropic bone formation. Urol. Int., 42: 458, 1987. Huggins, C. B.: The formation of bone under the influence of epithelium of the urinary tract. Arch. Surg., 22: 377, 1931. EDITORIAL COMMENT
The treatment of patients with erectile dysfunction by injection of vasoactive agents has become more common in recent years. Priapism or prolonged erection occurs in as many as 15% of the patients, with corporeal fibrosis demonstrated in 2%. As clinical experience with injection of vasoactive agents, especially papaverine and phentolamine, continues additional unique complications will surface. As a result of the recent development of this therapeutic modality, few of these complications have been reported in the literature. While heterotopic bone formation within the corpus cavernosum is not a new observation but has been identified previously as a result of penile trauma, an operation or Peyronie's disease, its relationship to papaverine injection is important for the urological community. As a result of the prolonged priapism and trauma to the distal corpora cavernosa caused by the Winter shunt, which was performed in an effort to eliminate the priapism in this case, the true relationship of papaverine injection to this heterotopic bone formation is not clear. However, there is little question that the priapism resulted from papaverine injection, and the subsequent Winter shunt and corporeal fibrosis were a result of delayed treatment of this complication. Most importantly, while vasoactive injection for the treatment of erectile dysfunction is safe in the majority of patients, complications of this method can be profound and disabling. The urologist who treats patients with pharmacological injection therapy must be diligent, and informed of unique and unusual complications that may occur. Rapid pharmacological treatment for patients with prolonged erection after papaverine injection generally will result in rapid return of the penis to the flaccid state with few complications. Culley C. Carson, III Division of Urology Duke University Medical Center Durham, North Carolina