Peyronie’s disease is a male disorder characterized by the formation of fibrous plaques in the white membrane of the penis. It has no clear etiology and usually causes malformation of the penis followed by various degrees of erectile dysfunction.
I. Epidemiology
Schwarzer et al. (2001) reported a 3.2% prevalence of penile sclerosis. The minimum age of onset is 18 years old, the maximum is 80 years old, and two-thirds of the patients are 40-60 years old.
Etiology and pathogenesis
The etiology of penile sclerosis is unclear and may be related to Dupuytren’s contracture, plantar fascial contracture, bulbar sclerosis, trauma, urethral instrumentation, diabetes mellitus, gout, Paget’s disease, infection, connective tissue disease, autoimmune disease, and the use of beta-blockers. The disease shows a family tendency to run in families, with 2% of patients with penile sclerosis having a family history. 20% of men descended from patients with Dupuytren’s contracture are likely to develop penile sclerosis. Initial injury to the penile tunica albuginea is an important cause of sclerosis. The penile tunica albuginea is a multilayered structure with an outer layer of longitudinal fibers, an inner layer of circumferential fibers, and two penile corpus cavernosum midlines connected by septal fibers. The septal fibers are intertwined with the circular fibers of the inner layer of the leukoplast. Acute and chronic bending injuries cause the inner and outer layers of the leukocyte to fracture, bleed, and infiltrate blood into the leukocyte gap, resulting in fluid or fibrinogen exudation from the subleukocyte, and fibrin deposition may be the key to initiate abnormal healing reflection of trauma. tGF-β1 is important in the pathogenesis of penile sclerosis, and it increases the transcription and synthesis of tissue collagen, proteoglycan, and fibrin, as well as the The synthesis of collagenase inhibitors, thus preventing the breakdown of connective tissue.
Pathophysiology
In early stages of sclerosis, inflammatory cells infiltrate around the blood vessels between the white membrane and the corpus cavernosum, forming cuff-like structures, followed by fibrosis, and in some severe cases, foci of calcification may be formed. Inflammatory cell infiltrates include T lymphocytes, macrophages, and other plasma cells that eventually initiate the cytokine system leading to the formation of fibrosis. These inflammatory infiltrations play an important role in this process along with active cytokine systems (especially TGF-β1 and fibroblast growth factor), and how to rationally regulate these factors provides the direction for subsequent treatment.
IV. Clinical manifestations and diagnosis
The clinical manifestations of penile sclerosis include penile plaques or nodules, penile curvature or shortening, erectile pain, and erectile dysfunction. pryor et al. reported that two-thirds of patients with sclerosis are located on the dorsal side of the corpus cavernosum and cause the penis to bend dorsally. ventral and bilateral paraprosthetic sclerosis is uncommon but can cause difficulty in sexual intercourse due to the large deviation from the natural angle of intercourse. Penile pain often occurs during the inflammatory phase of erection. 15-20% of patients with penile sclerosis were reported by Kadioglu et al to have erectile dysfunction. Causes of erectile dysfunction include psychological causes such as anxiety and restlessness; organic causes include severe penile deformity, hypospadias, and impaired penile vascular function. Severe deformity of the penis makes it difficult to have intercourse if penile curvature occurs ventrally or at a large lateral angle; extensive penile sclerosis lesions may lead to penile ring-shaped plaques forming a so-called shackled penis and preventing intercourse; 30% of patients with penile sclerosis may also have penile vascular disease causing erectile dysfunction. The plaque may cause decreased compliance of the tunica albuginea, which may prevent adequate compression of the subungual veins during erection and impair veno-occlusive function.
The diagnosis of penile sclerosis can often be confirmed by history and physical examination. Ultrasonography can estimate the location and size of penile sclerosis plaques and the presence of calcification, and is also indicated to determine the collateral arterial connections between the dorsal artery, penile cavernous artery, and cavernous sinus artery. Erection can be induced by cavernous injection of drugs to understand the curvature of the penis. Spongiodynamic perfusion instrumentation can be used to confirm the diagnosis of venous closure insufficiency with the aid of Doppler ultrasound.
V. Treatment
1.Non-surgical treatment
Sclerosis is a progressive disease that may resolve or heal spontaneously in some patients, and Ralph et al. believe that the active observation period is one year, during which conservative treatment can be used; treatment should focus on those patients with early inflammatory disease to prevent the destruction of the penile white membrane structure, especially the connection between the inner and outer membrane structures; once fibrosis, calcification, or ossification occurs, it will become irreversible, and drug or physical Once fibrosis, calcification, or ossification occurs, it becomes irreversible and neither medication nor physical therapy is effective.
Vitamin E (200mg, 3 times daily)
Vitamin E, a free radical scavenger with antioxidant properties, was first published by Scardino et al. in 1948 in an uncontrolled study of 23 participants, with the following results: 78% of patients showed improvement in penile curvature, 91% had a reduction in hardness and a complete disappearance of pain. The next trials did not yield the favorable results described above. In particular, in a placebo-controlled study with 40 patients, only 35% of the patients showed improvement in pain and a small effect on nodule size and penile curvature. Nevertheless, vitamin E is widely used because it is inexpensive and has no side effects.
Para-aminobenzoic acid (POTABA, 12g once daily for 3 months)
POTABA reduces 5-hydroxytryptamine levels by increasing monoamine oxidase activity, inhibits abnormal fibrous proliferation, and improves tissue application of oxygen. This use was first reported in a study of 21 patients in 1959: all patients had a reduction in pain, 82% had an improvement in penile curvature, and 76% had a reduction in sclerosis. The use of POTABA is limited, including the maximum dose limitation (12 grams per day), high cost, and serious gastrointestinal side effects, and is therefore not recommended.
Tamoxifen (TAMOXIFEN)
Tamoxifen is thought to promote the release of TGF- from fibroblasts, which plays an important role in the regulation of immune response, inflammation, and tissue repair by inactivating macrophages and T lymphocytes. In the earliest study of 36 people treated with tamoxifen, 20 mg used twice daily for three months, 20 patients (55%) showed improvement and none had worsening, with very significant improvement early in the disease (less than 4 months from onset). Biopsies were taken from the hard nodes of 12 patients with painful penile sclerosis, and 6 of the 8 who were able to measure acute inflammatory exudate responded very well to tamoxifen, while those who did not measure inflammatory exudate did not improve. CONCLUSION: Tamoxifen is beneficial in early inflammatory penile sclerosis. These results were not supported in the placebo-controlled trial of 25 participants, but the vast majority of patients in this trial had a long duration of disease in which any drug treatment was considered to be minimally effective.
COLCHICINE
Colchicine has an anti-inflammatory effect, affects collagenase activity, reduces collagen synthesis and inhibits fibroblast proliferation. The recommended dose is 0.6-1.2 mg twice daily for 3 months. kadioglu initiated a study of oral colchicine in 60 patients with penile sclerosis in the acute phase. Over the next 10.7 months, 30% of the patients had improved penile deformity and 95% had reduced pain. The best results were seen in patients with no cardiovascular risk factors, in the first six months of life and with a penile curvature of less than 30 degrees.
Verapamil (10mg in 10ml saline x 12)
Verapamil acts as a calcium channel antagonist to reduce intercellular calcium ion concentration and increase collagenase activity. It also inhibits fibroblast proliferation, and Levine et al. reported that verapamil was used for the treatment of penile sclerosis from 1994, and showed significant effects in a longer study at the same institute in the following years. Using a multipoint puncture technique, 10 mg of verapamil diluted to 10 ml and injected through the sclerotomies once every two weeks for a total of 12 injections, 60% of patients showed improvement in penile curvature and 71% showed improvement in sexual function. The main side effect is bruising, which is currently the most commonly used local treatment for injury in penile sclerosis Interferon (INTERFERON ) Interferon reduces extracellular collagen synthesis and increases collagenase synthesis, softening plaque and improving symptoms. The improvement in bending is mild, with an average improvement of 20 degrees. Its use is limited by its high cost and cold-like side effects.
Extracorporeal shock wave therapy (ESWT)
Bellorofonte et al. have been using ESWT for penile sclerosis since 1989 and have reported that it is effective in reducing penile curvature and pain, as well as improving sexual function. The theoretical basis for its action is unclear and may be related to the revascularization of the nodules and the absorption of calcification. lebret et al. reported a recent study using the siemens lithotripter in 54 patients with penile sclerosis (3000 Hz), 91% had reduced penile pain and 54% had improved penile curvature with a mean reduction of 31 degrees. Although the early results were good and well tolerated by the patients, the long-term efficacy needs to be observed.
Radiation therapy (13.5 GY)
Incrocci et al. reported that low-dose radiation therapy can be used to treat patients with persistent painful penile sclerosis, but it is not recommended for patients younger than 60 years of age because of the high incidence of ED (50%) after this treatment.
2.Surgical treatment
Indications for surgical treatment of penile sclerosis are: failure of conservative treatment; severe curvature of the penis during erection; accompanied by erectile dysfunction. The timing of surgery usually waits for the lesion to stabilize, usually 1 year after the onset.
Surgical methods include.
Penile white membrane folding; plaque excision with skin, vein or fascia to repair the defect; plaque excision with skin and vein graft to repair the defect; penile sclerosis with erectile dysfunction, penile prosthesis implantation can be done along with correction of penile flexion deformity.
Nesbit’s original approach was an oval excision of the contralateral flange of the flange and suture closure. During the period 1977-1992, 359 patients underwent this procedure and 295 (82%) had good results with successful intercourse. The main disadvantage of this procedure is the partial shortening of the penis, but in reality most of it does not affect intercourse. The satisfaction rate is 38%-100%.
Plaque excision of hard nodes
Plaque excision was once the standard of care, but the pathologic process of penile sclerosing plaques often extends beyond the plaque, and removal of a large portion of the white membrane can impair erectile function. a study of 418 patients reported by Austoni et al. showed that 17% of patients required further surgery to correct penile curvature and 20% had erectile dysfunction after using the plaque excision skin graft approach. Due to the high incidence of erectile dysfunction, contracture of the graft, late recurrence and poor long-term results, plaque excision with grafting is rarely done at this time.
Plaque excision
Because plaque excision is prone to erectile dysfunction, plaque excision with graft patching is currently advocated internationally for the treatment of penile sclerosis. Glebard and Hayden 1991 recommended this procedure, and Leu et al. reported that in 112 patients with penile sclerosis who had saphenous vein grafts, 95% of the patients had successful extension, with 13% of those who had intercourse complaining of reduced erectile function. The specific steps are: make parallel incisions on both sides of the penile corpus cavernosum, cut through Bucking’s fascia, free the vascular nerve bundle on the dorsal side of the penis, retract, expose the plaque and the surrounding white membrane, make a transverse H-shaped incision in the plaque, then take part of the saphenous vein and dissect it into a sheet vein, depending on the size of the defect, several veins may need to be combined and sutured, with the vein patch area slightly larger than the defect and the endothelial surface of the vessel facing the erectile tissue, using 3-0 PDS interrupted sutures. Commonly used grafts are mainly self-tissue, such as skin, vein wall, testicular sheath, and rectus abdominis tendon membrane.
Penile sclerosis with
Patients with erectile dysfunction that has failed to respond to pharmacological treatment are commonly treated with prosthetic implants. In most patients with mild to moderate curvature, the penile prosthesis can be embedded to straighten the penis without additional surgery, but in patients with severe flexion deformity, a mesh incision must be made in the white membrane at the penile plaque before implantation of the prosthesis to bring the penis to a level of complete straightening.