Campbell-Walsh Urology, 11th Edition

PART V

Reproductive and Sexual Function

31

Diagnosis and Management of Peyronie Disease

Laurence A. Levine; Stephen Larsen

Questions

  1. Peyronie disease (PD):
  2. is a wound healing disorder.
  3. is an autoimmune disease.
  4. frequently spontaneously recovers (30% to 50% of the time).
  5. may degenerate into cancer.
  6. is associated with Dupuytren contracture in 40% of men.
  7. The fibrous plaques in PD originate in:
  8. Buck fascia.
  9. the substance of the corpora cavernosa.
  10. the substance of the corpus spongiosum.
  11. the tunica albuginea surrounding the corpora cavernosa.
  12. the tunica albuginea surrounding the corpus spongiosum.
  13. Based on recent natural history studies on PD, a 54-year-old man with a 60-degree dorsal curve 18 months after onset suggests:
  14. 40% chance of spontaneous improvement of deformity.
  15. 70% chance of getting worse.
  16. 10% chance of getting worse.
  17. 10% or less chance of spontaneous improvement of deformity.
  18. 80% chance of staying the same.
  19. What is the prevalence of PD following radical prostatectomy?
  20. 4%
  21. 1% to 3%
  22. 11% to 16%
  23. > 20%
  24. 0%
  25. Plaque calcification:
  26. can be reliably identified on physical examination.
  27. can be found in 50% to 60% of men with PD.
  28. is not an indication of stable, mature disease.
  29. is associated with successful intralesional injection therapy.
  30. is a predictive factor for the need for surgical treatment.
  31. Psychological distress in men with PD:
  32. is infrequent.
  33. is typically resolved by successful surgery.
  34. is frequently associated with penile shortening.
  35. correlates with degree of erect curvature.
  36. has no association with relationship issues with the patient's partner.
  37. All of the following statements regarding the physical examination of a man presenting with PD are true EXCEPT that the examination:
  38. should include measurement of plaque size with calipers.
  39. should include direct assessment of curvature following injection of vasoactive agent.
  40. should include measurement of stretched penile length.
  41. can be supported with a picture of the erect penis by a smartphone.
  42. should include assessment of the patient's palms.
  43. Penile duplex ultrasound is a valuable test for men with PD. Yet it does not provide information about:
  44. penile deformity when erect.
  45. erectile response to vasoactive penile injection.
  46. penile vascular flow parameters.
  47. penile sensory integrity.
  48. plaque calcification.
  49. Pentoxifylline and the phosphodiesterase-5 (PDE5) inhibitors have been shown in an animal model of PD to reduce scarring by what proposed mechanism?
  50. Improved penile blood flow
  51. Anti-inflammatory
  52. Elevated local levels of nitric oxide (NO)
  53. Anti-transforming growth factor-β (TGF-β)
  54. Mechanotransduction
  55. Penile injection therapy (i.e., prostaglandin E1, TriMix-gel, etc.) for ED is not directly responsible for:
  56. cavernosal fibrosis.
  57. Peyronie disease.
  58. penile pain.
  59. priapism.
  60. high success rate.
  61. A 35-year-old man with Peyronie disease is able to achieve an erection adequate for intercourse with minimal discomfort and reported dorsal erect penile curvature of 20 degrees. The initial treatment should be:
  62. reassurance.
  63. oral vitamin E.
  64. intralesional steroids.
  65. oral tamoxifen.
  66. intralesional collagenase.
  67. A 66-year-old man presents with a 2-year history of PD and a 55-degree dorsal curvature. He also notes that his average-grade erection with sexual stimulation at home is a grade 5/10, which would not be adequate for intromission even if the penis were straight. Duplex ultrasound analysis demonstrates arterial insufficiency and an inadequate erectile response to 90 mg of intracorporal papaverine. The most appropriate treatment option for this patient who wants to resume sexual activity would be:
  68. oral vitamin E or potassium para-aminobenzoate (Potaba).
  69. vacuum constriction device.
  70. penile prosthesis with penile straightening.
  71. intralesional verapamil injections.
  72. oral colchicine.
  73. Tunica plication is preferred for mild to moderate curvature correction because of:
  74. less shortening compared with grafting.
  75. better sensory protection.
  76. diminished risk of postoperative ED.
  77. greater potential for loss of erect length.
  78. Postoperative rehabilitation is designed to aid in postoperative healing and outcomes in the following ways, EXCEPT:
  79. to prevent shortening and possibly recover some lost length.
  80. to encourage straight healing.
  81. to enhance cicatrix contracture.
  82. to preserve vascular integrity.
  83. to encourage partner participation.
  84. All of following are true regarding penile traction therapy after surgical penile straightening, EXCEPT:
  85. increases or preserves postoperative length.
  86. encourages tissue remodeling.
  87. should be used for 3 or more hours/day for optimum results.
  88. increases the risk of sensory change.
  89. results appear dose-related.
  90. What is the most common adverse event occurring after manual modeling during placement of a penile prosthesis in a man with PD?
  91. Tunica tear proximal
  92. Urethral injury
  93. Sensory deficit
  94. Recurrent curvature
  95. Distal urethral perforation
  96. Indications to perform a plaque incision or partial excision and grafting include all of the following, EXCEPT:
  97. severe curvature in excess of 70 degrees.
  98. indentation resulting in an unstable penis or hinge effect.
  99. a short penis (< 9 cm) with severe curve and poor rigidity.
  100. a short penis with severe curvature and excellent rigidity.
  101. extensive plaque calcification associated with severe deformity.
  102. The primary postoperative side effect occurring following a grafting procedure for PD is:
  103. erectile dysfunction.
  104. incomplete correction of hinge effect.
  105. shortening.
  106. diminished sexual sensation.
  107. infection.
  108. The primary reason to consider a grafting procedure to correct penile deformity in a man with PD is:
  109. a severe ventral curve.
  110. suboptimal rigidity even with PDE5 inhibitors.
  111. severe curve greater than 60 to 70 degrees with or without hinge effect.
  112. a 90-degree lateral curve presenting 6 months after onset.
  113. to gain length as a result of surgery.
  114. The ideal graft includes all of the following EXCEPT:
  115. thin, strong, and easy to suture.
  116. no rejection.
  117. resistant to infection.
  118. preserves erectile function.
  119. contracts during healing.

Answers

  1. a. Is a wound healing disorder. PD is currently recognized as a wound healing disorder of the tunica albuginea (Devine and Horton, 1988)*that results in the formation of an exuberant scar, occurring presumably after an injury to the penis, which activates an abnormal wound healing response (Ralph et al, 2010; Levine and Burnett 2013; Greenfield and Levine, 2005; Van De Water, 1997). PD is not a premalignant condition, spontaneous resolution is a rare event, and improvement likely does not take place in more than 13% of men over the first 12 to 18 months. Though an association with Dupuytren contracture has been described, studies vary widely on this association.
  2. d. The tunica albuginea surrounding the corpora cavernosa.PD plaques originate in the tunica albuginea. Sixty percent to 70% of plaques are located on the dorsal aspect of the tunica albuginea and are usually associated with the septum (Pryor and Ralph, 2002). It is possible that pressures on the penis during intercourse result in a delamination between the two layers, activating the abnormal wound-healing process, which is trapped within the tunic, fostering the progressive scarring.
  3. d. 10% or less chance of spontaneous improvement of deformity. Spontaneous regression has been looked at in several contemporary natural history studies, which have suggested that no more than 13% will experience improvement of deformity.Full spontaneous resolution is extremely rare. If no treatment is offered, up to 50% will experience worsening of their deformity (Mulhall et al, 2006).
  4. c. 11% to 16%.Tal and associates (2010) demonstrated an incidence of PD of 15.9% with a mean time to development of disease of 13.9 months. Ciancio and Kim (2000) also examined the effects of prostatectomy on penile fibrosis and sexual dysfunction. Eleven percent of all patients undergoing prostatectomy developed fibrotic changes in the penis. This fibrosis led to penile curvature in 93%, “waistband” deformity in 24%, and palpable plaques in 69%.
  5. c. Is not an indication of stable, mature disease. Only recently has it been recognized that calcification may occur early after the onset of the scarring process, and therefore, the previously held notion that calcification is an indication of chronic, severe, and/or mature disease appears untrue (Levine et al, 2013).Several investigators have indicated that intralesional injection therapy of verapamil and interferon is less likely to be successful in men with significant calcification (Levine et al, 2002b; Hellstrom et al, 2006). A "rock-hard" plaque may be an indicator of calcification but will need to be confirmed with some form of imaging, preferably ultrasound. A calcified plaque is readily identified by ultrasound because of the hyperdensity of the plaque with shadowing behind it. Calcification itself does not predict the need for surgery. Approximately 34% of PD patients will have some degree of plaque calcification.
  6. c. Is frequently associated with penile shortening. Penile shortening and inability to have intercourse are the two most common and consistent risk factors for emotional distress and relationship problems associated with PD (Smith et al, 2008; Rosen et al, 2008).Psychosocial stress is common and is reported by 77% to 94% of men with PD (Gelbard et al, 1990; Tal et al, 2012; Nelson and Mulhall, 2013). PD also commonly affects the patient's sexual partner, causing feelings of helplessness, as well as feeling personally responsible for the PD due to trauma during intercourse and sadness over loss of intimacy (Rosen et al, 2008). For some patients even a lesser degree of curvature may be highly bothersome or provoke distress (Hellstrom et al, 2013). Despite "successful treatment" that may allow the patient to be sexually functional again, there is often persistent psychological distress, presumably due to the residual changes compared with that man's pre-PD penis (Jones, 1997; Gelbard et al, 1990).
  7. a. Should include measurement of plaque size with calipers.Measurement of the size of the plaque with any modality has been found to be inaccurate, as the plaque is rarely a discrete lesion (Bacal et al, 2009; Levine and Burnett, 2013; Ralph et al, 2010; Hatzimouratidis et al, 2012). Deformity assessment via ultrasound after injection of vasoactive agent has been shown to be the best method of assessing curvature as well as erectile response. Pictures taken from multiple vantage points may give a better idea of deformity during initial consultation. Because of the association with other collagen vascular disorders, the patient's palms should be examined.
  8. d. Penile sensory integrity.The benefits of a complete duplex ultrasound assessment include identification of calcification during initial surveillance in the flaccid state, assessment of penile vascular flow parameters following intracavernosal injection of vasoactive agent, observing the erectile response to the vasoactive injection compared to the patient's sexually induced erection at home, and finally providing the best opportunity to objectively assess deformity. These parameters are absolutely critical to the decision process for the patient who is considering surgery. Penile sensation is best evaluated with biothesiometry.
  9. c. Elevated local levels of nitric oxide (NO). Pentoxifylline is a nonspecific phosphodiesterase inhibitor with combined anti-inflammatory and antifibrogenic properties.NO synthesized by inducible nitric oxide synthase (iNOS) reacts with reactive oxygen species (ROS), thus reducing ROS levels and presumably inhibiting fibrosis. The antifibrotic effects of NO may be mediated at least in part by the reduction of myofibroblast abundance and lead to a reduction in collagen I synthesis (Vernet et al, 2002).
  10. b. Peyronie disease.Injection therapy has no association with leading to PD. It may, however, lead to some degree of cavernosal fibrosis, pain, and priapism. When used in the appropriate population, intracavernosal injection therapy for ED does have a high success rate.
  11. a. Reassurance.In this case, a young man presents with PD with a minimal curvature and minimal discomfort. Pursuing aggressive therapy is not indicated because the disease process may not worsen. Therefore, reassurance is the proper answer. This patient should also be counseled to follow up should he see any exacerbation of his symptoms. At this time, intralesional collagenase is not indicated for curvature less than 30 degrees, the two noted oral therapies are not noted to be beneficial, and intralesional steroids are not recommended because of lack of objective evidence of benefit.
  12. c. Penile prosthesis with penile straightening.This man presents with stable PD, a borderline moderate to severe curvature, but a poor-quality erection at home and an inadequate erectile response during duplex ultrasound with a high dose of vasoactive intracorporal drug injection. Therefore, for the motivated patient who has both erectile dysfunction (ED) and PD, placement of a penile prosthesis with straightening maneuvers is the most likely treatment to address both problems. Use of oral therapy had not been proven to be beneficial in this circumstance. Intralesional injection of any sort may potentially benefit his deformity, but given that he has inadequate erectile response, intralesional injections would not result in ability to resume sexual activity.
  13. c. Diminished risk of postoperative ED.A tunica plication procedure is the preferred approach because it has the least likelihood of causing injury to the underlying cavernosal tissue, which presumably is responsible for postsurgical ED seen most commonly with a grafting procedure. There is indeed a greater potential for loss of erect length with a plication and less likelihood of damaging the penile sensory nerves, but the diminished risk of postoperative ED is the strongest reason to pursue a plication rather than grafting procedure, particularly in patients with less than severe curvature.
  14. c. To enhance cicatrix contracture.Postoperative rehabilitation with massage and stretch, nightly use of a PDE5 inhibitor, and traction therapy are designed to enhance postoperative healing in all listed ways except for c, which is the correct answer because enhancing cicatrix contracture would not enhance healing or postoperative outcomes.
  15. d. Increases the risk of sensory change. Penile traction therapy has emerged as an effective treatment option for PD either preoperatively alone or in combination with other treatments, or postoperatively to aid in the rehabilitation of the penis.Traction therapy has been shown to increase or preserve postoperative length and encourage tissue modeling, and it does appear to be dose-related. In addition, one study suggested that the minimum average time for daily use following surgery would be 3 hours or more per day. There is no evidence that traction therapy causes injury to the sensory nerves, nor is there evidence to suggest that it increases the risk of sensory change.
  16. b. Urethral injury.Manual modeling was introduced in the mid-1990s as a straightening maneuver to correct residual curvature after placement of a penile prosthesis. In performing this procedure, the primary reported risk is injury to the urethra at the meatus, where the prosthetic cylinder tips may extrude through the meatus as a result of pressure placed on the distal shaft during the modeling process. Although sensory deficit, recurring curvature, and tunica tear are possible complications, they have not been reported, nor has a proximal urethral perforation.
  17. c. A short penis (< 9 cm) with severe curve and poor rigidity.This is the only option noted that would not be appropriately treated by a grafting procedure for PD, primarily because of the poor rigidity. One of the primary indications to perform a grafting procedure would be the patient having a strong erection preoperatively with severe curvature in excess of 70 degrees, having indentation causing an unstable penis or hinge effect, or a short penis. The key here is the poor rigidity, which would be an absolute contraindication to performing a grafting procedure, as it is unlikely that the grafting will improve the quality of erection; it is more likely to cause further ED in this circumstance.
  18. a. Erectile dysfunction.Although the other listed side effects have been reported, the primary concern with patients undergoing this procedure is postoperative ED. Therefore, proper patient selection preoperatively would include only those men who have excellent-quality rigidity with or without PDE5 inhibitor therapy and have a normal vascular response during duplex ultrasound assessment.
  19. c. Severe curve greater than 60 to 70 degrees with or without hinge effect. Ventral curvatures when repaired with grafting have a much higher rate of complete ED.Those with suboptimal rigidity tend to also develop more erectile problems post-grafting. A 90-degree curve may be an indication, but it should be with at least 1 year from the time of onset with 6 months of stable disease, which would rule out option d, as this patient is still in the acute phase. Finally, it should be recognized that although a patient is more likely to recover some length after performing a grafting procedure, neither grafting nor plication operations should be expected to result in substantial gain of length; the primary goal is straightening.
  20. e. Contracts during healing.Contraction during the healing process would not be included in the criteria for an ideal graft.

Chapter review

  1. There are two phases in the natural history of Peyronie disease (PD): the acute phase, in which changes occur, and the stable chronic phase.
  2. The incidence of PD is between 3% and 9% with a peak age of 50 years.
  3. There is a high association (33%) of diabetes with PD.
  4. Preoperative erectile function correlates strongly with postoperative results.
  5. Combination therapy includes intralesional injection of verapamil, oral pentoxyfilline and l-arginine, and traction. Pentoxifylline is a nonspecific phosphodiesterase inhibitor with combined anti-inflammatory and antifibrogenic properties. Penile traction therapy has emerged as an effective treatment option for PD.
  6. Patients with poor-quality erections preoperatively who have grafting procedures are likely to have significant problems postoperatively with erectile function.
  7. PD is currently recognized as a wound healing disorder of the tunica albuginea.
  8. Sixty percent to 70% of plaques are located on the dorsal aspect of the tunica albuginea and are usually associated with the septum.
  9. The natural history of PD suggests that no more than 13% of patients will experience improvement of deformity.
  10. Eleven percent of all patients undergoing prostatectomy developed fibrotic changes in their penis.
  11. Penile shortening and inability to have intercourse are the two most common and consistent risk factors for emotional distress and relationship problems associated with PD.
  12. Primary indications to perform a grafting procedure in a patient with a strong erection are severe curvature in excess of 70 degrees, an indentation causing an unstable penis or hinge effect, and a short penis. Poor rigidity is an absolute contraindication to performing a grafting procedure.
  13. Ventral curvatures, when repaired with grafting, have a much higher rate of complete erectile dysfunction.

* Sources referenced can be found in Campbell-Walsh Urology, 11th Edition, on the Expert Consult website.