Insights of priapism mechanism and rationale treatment for recurrent priapism

Priapism is defined as abnormal prolonged penile erection occurring beyond or unrelated to sexual interest. The disorder is enigmatic yet devastating because of its elusive etiology, irreversible erectile tissue damage, and resultant erectile dysfunction （ED）. Current management strategies suffer from a poor understanding of the pathophysiology, especially at the molecular level. The traditional treatments are based more on empirical rather than evidence-based knowledge. The outcomes for restoration of normal erectile function are poor, especially for stuttering priapism. Therefore, it is critical to understand priapism from a molecular level, to formulate treatment strategies and to establish rational prevention strategies for high-risk populations, such as sickle cell disease （SCD） patients and cases of the stuttering variant. This review focuses on the recent advances at the molecular level in priapism and penile erection, and applies the recent knowledge to the treatment of stuttering priapism.     

Priapism: New concepts in the pathophysiology and new treatment strategies

Priapism is defined as prolonged and persistent erection of the penis without sexual stimulation. This is a poorly understood disease process, and we have little information on the etiology and pathophysiology of this erectile disorder. Two main types of priapism exist: low-flow (ischemic) and high-flow (nonischemic) priapism. When the physician first diagnoses which type of priapism exists, distinguishing the type of priapic event is paramount in order to choose the correct treatment options. Until recently, we had not sufficiently understood the pathogenesis of this erectile disorder and therefore, could not effectively manage its pathologic consequences of erectile tissue damage and erectile dysfunction. In this review, the proposed pathogenesis of ischemic priapism is reviewed, and a survey regarding novel treatment modalities is given.     

Treating stuttering priapism

Stuttering priapism is an uncommon recurrent form of ischaemic priapism consisting of episodes of unwanted, painful erections that typically last for <3 h. It occurs repeatedly with intervening periods of detumescence. If these episodes are not treated, it may evolve into a classic ischaemic priapism and eventually lead to irreversible corporal fibrosis with permanent erectile dysfunction. A comprehensive literature search was conducted in August 2010 using the PubMed database, MEDLINE and generic search engines. The search terms used to source information on this topic were, stuttering priapism (44 hits) and recurrent priapism (161 hits). Although there are numerous publications on this topic the majority of them are small trials and case reports. We identified 117 case reports, 28 reviews, 37 anecdotal reports, 22 small size clinical trials and one in vitro work. Our understanding of the underlying pathophysiology of stuttering priapism has improved in recent years. Further multicentre randomized clinical trials are required to evaluate the efficacy of different treatment options and to define safe and effective management strategies for patients with low-flow recurrent priapism.     

Pathophysiology of priapism: dysregulatory erection physiology thesis

PURPOSE: While a modest amount of medical literature has been written on the topic of priapism, reports heretofore have focused predominantly on diagnostic and management related aspects of the disorder, providing meager information in regard to its pathophysiology. Accordingly the intent of this review was to explore the etiological and pathogenic factors involved in priapism. MATERIALS AND METHODS: The review entailed an overview of traditional and modern concepts that have been applied to the pathophysiology of priapism and an evaluation of assorted observational and experimental data relating to this field of study. The basic exercise consisted of a literature search using the National Library of Medicine PubMed Services, index referencing provided through the Historical Collection of the Institute of Medicine of The Johns Hopkins University and a survey of abstract proceedings from national meetings relevant to priapism. RESULTS: Insight into the pathophysiology of priapism was derived from a synthesis of evolutionary clinical experiences, mythical beliefs, clinical variants and scientific advances associated with the field of priapism. The results can be summarized. 1) Clinicopathological manifestations of priapism support its basic classification into low flow (ischemic) and high flow (nonischemic) hemodynamic categories, commonly attributed to venous outflow occlusion and unregulated arterial overflow of the penis, respectively. 2) Factual information is insufficient to substantiate etiological roles for urethral infection, bladder distention, failed ejaculation, satyriasis and sleep apnea in priapism. 3) Features of the variant forms of priapism invoke changes in nervous system control of erection and penile vascular homeostasis as having pathogenic roles in the disorder. 4) Clinical therapeutic and basic science investigative studies have revealed various effector mechanisms of the erectile tissue response that may act in dysregulated fashion to subserve priapism. CONCLUSIONS: This exercise suggested that, while priapism is commonly defined in terms of adverse mechanical contexts affecting penile circulation, it may also be viewed at least in some situations as an unbalanced erectile response involving derangements in possibly diverse systems of regulatory control. An integrative scientific approach that encompasses tissular, cellular and molecular levels of investigation may allow further understanding of the pathophysiology of the disorder. Ongoing elucidation of this pathophysiology can be expected to promote the development of new priapism therapies.     

Doppler blood flow analysis of erectile function: who, when, and how

The underlying processes in vasculogenic erectile dysfunction (ED) are arterial insufficiency, venoocclusive disease, or combinations of both. Doppler blood flow analysis is a diagnostic modality useful in elucidating the cause of ED and the magnitude of its severity. This article describes the procedural techniques, typical findings, and relevant pathophysiology for in-office Doppler studies. Specific conditions include arterial insufficiency, venous occlusive disease, Peyronie's disease, and priapism.     

The use of high‐resolution magnetic resonance imaging in the management of patients presenting with priapism

Study Type – Diagnosis (exploratory cohort)
Level of Evidence 2b OBJECTIVE To investigate the use of magnetic resonance imaging (MRI) of the penis during an episode of priapism and assess the viability of the corpus cavernosum (CC) smooth muscle, as prolonged ischaemic priapism is associated with a high rate of long‐term erectile dysfunction (ED), and the viability of CC smooth muscle influences the subsequent management in ischaemic priapism. PATIENTS AND METHODS The study was set in a single centre based in a large university teaching hospital. We investigated the correlation of T2‐weighted gadolinium‐ enhanced MRI with the histology from CC biopsies in the same patients. In all, 38 patients (mean age 42 years) presenting with priapism over a 3‐year period had MRI of the penis. The scans were reported by two dedicated uro‐radiologists who graded the MR images as showing viable or nonviable erectile tissue. One pathologist assessed the CC biopsies for necrosis. The findings were then correlated. Where no biopsies were taken a clinical follow‐up was used to assess erectile function. RESULTS In 23 patients undergoing both a CC biopsy and MRI, the sensitivity of MRI in predicting nonviable smooth muscle was 100%. In a further 10 patients MRI showed nonviable CC smooth muscle, but no biopsy was taken in these patients; on clinical follow‐up all of these patients subsequently developed ED. In a further five patients the imaging showed viable smooth muscle and these patients subsequently maintained erectile function on clinical follow up. CONCLUSIONS Penile MRI provides an accurate imaging method to assess smooth muscle viability in patients presenting with priapism.     

A pathophysiology-based approach to the management of early priapism

Priapism is a rare condition that involves persistent penile erection for greater than 4 h. Distinct variants exist, each with unique characteristics. Ischemic priapism is a painful medical emergency that may occur as a result of veno-occlusion leading to hypoxia and tissue death. Recurrent bouts of ischemic priapism, or stuttering priapism, require treatment for individual attacks as well as long-term prevention. Non-ischemic priapism is associated with trauma and may be managed conservatively. Recent advances into the pathophysiology of priapism have allowed the development of treatment algorithms that specifically target the mechanisms involved. In this review, we outline the basics of smooth muscle contraction and describe how derangement of these pathways results in priapism. A pathophysiological approach to the treatment of priapism is proposed with duration-based algorithms presented to assist in management.     

Stuttering Priapism: Insights into Pathogenesis and Management

Priapism is defined as a persistent, painful erection that continues beyond, or is unrelated to, sexual stimulation. It may be categorized as either ischemic (low/absent flow) or nonischemic (high flow). Stuttering priapism is a variant of the ischemic type that is characterized by repetitive, transient, painful, self-limiting episodes of priapism. It is associated with various hematological disorders, including sickle cell disease and pharmacological treatments. The consequences of ineffective treatment of priapism are erectile dysfunction and impaired quality of life due to chronic pain and physical disfigurement. Many of the existing medical therapeutic options for treatment of stuttering priapism are nonmechanistic and associated with significant adverse effects. However, the scientific knowledge of stuttering priapism has transitioned in the past few years, from a condition that is poorly understood to one that has borne a burst of evolving molecular science. In this review, the pathophysiology of priapism is discussed, with particular emphasis on new molecular effectors and mechanisms. Novel treatment methods, as well as potential future agents, based on the emerging molecular evidence are discussed.     

Therapy insight: Priapism associated with hematologic dyscrasias

Priapism is defined as a genuine erectile disorder, in which erection persists uncontrollably without sexual purpose. This disorder is often overlooked in comparison to other male sexual dysfunctions, principally because of its seeming rarity. Priapism, however, occurs frequently in certain patient populations, including those with hematologic dyscrasias. Most commonly, priapism affects patients with sickle cell disease. The reported prevalence rate in this group ranges between 29% and 42% of males. The significance of priapism is further emphasized by the fact that this disorder commonly causes erectile tissue damage and leads to the loss of functional erections. These observations highlight the need for proper clinical recognition of priapism in order to enable appropriate management. Here, the current knowledge of priapism as it relates to hematologic and coagulative diseases is discussed, with a focus on the diagnosis and treatment of the disorder.     

Unsatisfactory outcomes of prolonged ischemic priapism without early surgical shunts: our clinical experience and a review of the literature

Ischemic priapism is a rare occurrence which can cause severe erectile dysfunction (ED) without timely treatment. This retrospective study reports our experience in treating prolonged ischemic priapism and proposes our further considerations. In this paper, a total of nine patients with prolonged ischemic priapism underwent one to three types of surgical shunts, including nine Winter shunts, two Al-Ghorab shunts and one Grayhack shunt. During the follow-up visit (after a mean of 21.11 months), all patients'' postoperative characters were recorded, except one patient lost for death. Six postoperative patients accepted a 25-mg oral administration of sildenafil citrate. The erectile function of the patients was evaluated by their postoperative 5-item version of International Index of Erectile Function Questionnaire (IIEF-5), which were later compared with their premorbid scores. All patients had complete resolutions, and none relapsed. The resolution rate was 100%. Seven patients were resolved with Winter shunts, one with an Al-Ghorab shunt and one with a Grayhack shunt. The mean hospital stay was 8.22 days. There was only one urethral fistula, and the incidence of postoperative ED was 66.67%. Four patients with more than a 72-h duration of priapism had no response to the long-term phosphodiesterase type 5 (PDE-5) inhibitor treatment. These results suggest that surgical shunts are an efficient approach to make the penis flaccid after prolonged priapism. However, the severe ED caused by prolonged duration is irreversible, and long-term PDE-5 inhibitor treatments are ineffective. Thus, we recommend early penile prosthesis surgeries for these patients.     

Idiopathic stuttering priapism treated with salbutamol orally: a case report

Recurrent ischaemic priapism also known as stuttering priapism is an uncommon form of ischaemic priapism, and its treatment is not yet clearly defined. If left untreated, it may evolve into classic form of acute ischaemic priapism and lead to erectile dysfunction due to fibrosis of corpora cavernosa. Several drugs have been proposed with variable results and only supported with level three or four of evidence. Hormonal therapy such as cyproterone acetate, oestrogen, bicalutamide or Lh‐Rh agonist are often effective but can cause side effects such as hypogonadal state and infertility. Other medical options are 5‐alpha‐reductase and phosphodiesterase‐5 inhibitors, ketoconazole, baclofen, digoxin, gabapentin and beta‐2‐agonist terbutaline. We report the first case of stuttering priapism treated with beta‐2‐agonist salbutamol.     

Traumatic laceration of intracavernosal arteries: the pathophysiology of nonischemic, high flow, arterial priapism

Two forms of priapism are known to occur. The more common type, veno-occlusive priapism, presents with a prolonged painful erection, and it is characterized by ischemia and pooling of blood within the corpora cavernosa. The less common form, high flow priapism, is characterized by lack of pain and ischemia. The pathophysiology of this disorder is poorly understood and the treatment is unclear. We report 2 cases of nonischemic priapism, one of which occurred after blunt perineal trauma and the other after intracavernosal self-injection with papaverine and phentolamine. Based on our 2 cases as well as a review of the literature (5 cases), we propose that the pathophysiological mechanism of this disorder is unregulated arterial inflow into the corpora, classify it as arterial priapism, and describe a diagnostic and therapeutic algorithm for its management.     

Temporary cavernosal-cephalic vein shunt in low-flow priapism treatment

Background

Surgical shunting might be considered as the only option in the treatment of extended ischemic priapism that does not respond to aspiration and medication.

Objective

A modified, simple, minimally invasive, and easily applicable artificial cavernosal–venous shunt technique for treating priapism is described in this report.

Design, setting, and participants

A total of 15 patients with extended and nonresponsive low-flow priapism were treated with this technique between January 1998 and February 2007.

Intervention

When the conservative treatment of low-flow priapism does not yield the expected results, then the temporary cavernosal–cephalic vein shunt should be applied. The standard equipment required for this modified technique includes three angiocaths, two shorn blood serum sets, and saline solution with heparin. The blood in the cavernosa and the saline solution infusion are incorporated into the systemic circulation with the aid of serum sets and angiocaths.

Measurements

Priapism duration, history, causes, its relation with sexual stimulation, pain, and any prior management of priapism were assessed in all patients. A complete blood count and blood gases assessment were conducted in corporal aspirates, and duplex penile ultrasonography was performed, which showed attenuated blood flow in the cavernosal artery.

Results and limitations

This technique was applied in 15 patients. Complete detumescence was achieved in 13. In the two cases in whom the technique did not yield the expected results, there was a need for a sapheno–cavernosal shunt. These patients later complained of erectile dysfunction and penile pain that continued for 6 mo. Of the 13 patients in whom detumescence was achieved, 3 reported erectile dysfunction according to International Index of Erectile Function (IIEF) scores at the 12-mo follow-up.

Conclusions

Artificial cavernosal–cephalic vein shunt in the treatment of priapism is simple, safe, effective, easily applicable, and warrants primary consideration when the second-line treatment of priapism is initiated.     

Tricorporal priapism postradical cystoprostatectomy: First sign of recurrent urogenital malignancy

Priapism usually involves the whole length of a corpus or two corpora. Rarely is priapism segmental, especially proximally, and seldomly does it involve all three corpora. The causes of priapism are varied, but priapism due to solid malignancy is an extremely uncommon entity. The usual malignancy is urogenital. The disorder is frequently a manifestation of extensive pelvic extension of the primary disease; less commonly, it is associated with pelvic recurrence after seemingly curative surgery. In cases of malignant recurrence, priapism is rarely the first sign of such recurrence. We report a case of proximal tricorporal priapism, secondary to penile metastasis of a bladder malignancy postradical cystoprostatectomy. In this case, priapism was the first sign of disease recurrence and occurred in the absence of pelvic recurrence. This is the first such report of which we are aware.     

New aspects in the treatment of priapism

Recent advances in the understanding of erectile physiology have improved the prompt diagnosis and treatment of priapism. During initial assessment, the physician must distinguish between veno-occlusive low flow (ischemic) and arterial high flow (nonischemic) in order to choose the correct treatment option for each type of priapism. Patient history, physical examination, penile haemodynamics and corporeal metabolic blood quality assist the distinction between static and dynamic priapism. Normally, priapism is effectively treated with intracavernous vasoconstrictive agents or surgical shunting. However, when these two methods fail, subsequent treatment procedures are a matter for debate. Alternative options, such as intracavernous injection of methylene blue or selective penile arterial embolization, for the management of high and low flow priapism are described and a survey of current treatment modalities is presented.     

利用微弹簧圈选择性动脉栓塞治疗高流量阴茎异常勃起患者勃起功能观察

目的 观察利用微弹簧圈超选择性动脉栓塞治疗高流量阴茎异常勃起对患者勃起功能和性生活质量的影响.方法 会阴部外伤引起阴茎异常勃起患者8例,平均年龄(33.38±12.42)岁,发病距就诊时间2d～8年.根据病史、临床表现、阴茎海绵体血气分析和彩色多普勒超声,诊断为高流量阴茎异常勃起,均在知情同意下通过阴部内动脉造影明确破损动脉,同时利用微弹簧幽选择性动脉栓塞治疗,栓塞后阴茎恢复疲软状态,临床治愈.采用国际勃起功能评分表(IIEF-5)和性生活质量调查表(SLQQ-QOL)对患者发病前,栓塞术后6个月、18个月随访评价勃起功能和性牛活质量.结果 患者栓寨后3个月开始有规律性生活,6个月和18个月IIEF.5评分分别为(19.57±5.35)分和(19.14±5.24)分,与异常勃起发病前(19.86±4.84)分相比无统计学差异(P>0.05).患者栓塞后6个月和18个月SLQQ-QOL评分分别为(34.14±7.73)分和(32.43±8.66)分,与发病前比较无显著差异(P>0.05).结论 微弹簧圈超选择性阴茎海绵体动脉栓塞术对治疗高流量阴茎异常勃起安伞有效,术后对年轻患者勃起功能无显著影响.     

A case of proximal partial priapism successfully treated with autologous clot embolisation

Partial priapism is a rare disorder in literature and generally described as a contusion or thrombosis of the cavernous body of the penis secondary to blunt trauma. Because of the rarity of disease, there is not much information about the treatment. Conservative management with nonsteroidal anti-inflammatory drug is often applied treatment. Here, we presented a proximal partial priapism treated successfully with autologous clot embolisation secondary to pelvic trauma.     

Priapism. From Priapus to the present time

Advances in the pharmacotherapeutic options available to treat erectile dysfunction over the past decade have transformed the field of impotence. The initial foray into this field with intracavernous injections of papaverine rapidly expanded the number of men seeking attention for priapism, a previously rare clinical condition. The recent widespread use and acceptance of oral agents for the treatment of erectile dysfunction, with a reduced incidence of priapism has decreased the number of men at risk for injection-related prolonged erections. The use of recreational drugs (cocaine) and perineal trauma leading to presentations of priapism seem to be rising in incidence. The urologist remains the consultant-specialist ultimately responsible for these men and should be cognizant of the array of treatments described for this condition. Early determination of the state of corporal oxygenation is essential and will define the optimal management approach. A wide range of medical conditions and risk factors may be etiologic and should be elicited from the patient at the initial interview. Low-flow ischemic priapism requires a rapid resolution, often achieved through use of alpha-agonists orally or by direct injection into the penile circulation, whereas nonischemic priapism can be treated more conservatively. Research into this condition has only recently been initiated. Through greater understanding of the pathophysiology of priapism, the clinician may become armed with etiology-specific medical alternatives providing timely detumescence for men with prolonged erections.     

9例阴茎异常勃起诊治体会

目的 探讨阴茎异常勃起的诊断和治疗方法.方法 回顾性分析9例阴茎异常勃起患者的诊治过程.结果 9例患者均通过病史、体检、海绵体抽吸血气分析及多普勒超声检查确诊.经镇静、局部冷敷、海绵体抽吸血液、海绵体内注射药物及手术等不同方法治疗后,8例缺血性阴茎异常勃起患者中5例完全消退,3例部分消退;1例非缺血性阴茎异常勃起患者部分消退.5例随访6个月,其中4例出现ED.结论 阴茎海绵体血气分析、海绵体彩色多普勒检查对阴茎异常勃起有重要诊断价值,早期及正确应用海绵体注射药物和阴茎海绵体尿道海绵体分流术加术中冲洗是治疗缺血性阴茎异常勃起的可靠方法,但是由于大多数病人持续勃起时间较长,ED的发生率偏高.     

Clinical course linkage among different priapism subtypes: Dilemma in the management strategies

Objectives: Priapism is a rare condition whose management differs according to the etiology. We report the clinical course of three forms of priapism to assess the feasibility and safety of recent management strategies. Methods: The study included eight patients complaining of persistent erection for ≥4 h who were treated in our institution between January 1996 and July 2007. Results: Overall, we categorized 12 cases of priapism in eight patients divided as follows: five cases of ischemic priapism (IP), three of stuttering priapism (SP), and four of non‐ischemic priapism (NIP). Two of five IP patients needed a shunt procedure, which led to the subsequent erectile dysfunction. The other three were treated successfully with a corporal injection of sympathomimetic agents and subsequently suffered from SP. One of the three SP patients suffered from mimicked NIP with increased arterial blood flow during the initial treatment for IP. Four of the NIP patients including the mimicked one achieved complete detumescence, through arterial embolization in two and conservative management in two. Conclusions: Current management seems effective and safe in the short‐term. However, the long‐term outcome of the treatment for IP is still disappointing. Careful long‐term observation is needed for an appropriate management.