Arthur L. Burnett, II, MD, MBA

Chronic orchialgia is not only detrimental to quality of life in men with the condition but also is challenging for providers to diagnose and treat. 

, a reproductive urologist with Austin Fertility & Reproductive Medicine in Texas, works with and treats these patients and studies the condition. In an interview with 

 professor of urology at Johns Hopkins University School of Medicine in Baltimore, Maryland, Kavoussi discussed his diagnostic work-up process and conservative versus surgical management in men with chronic testicular pain.

What is chronic orchialgia, and how does it fit in with other genitourinary pain syndromes?

The nomenclature used for this is important. Chronic orchialgia, if we are looking at the base of the term, is chronic testicular pain. However, it is used more loosely clinically to include scrotal pain and scrotal content pain. Other frequently associated terms include 

. We also have to be cautious about distinguishing between scrotal content pain and chronic pelvic pain syndrome (CPPS).

A great deal of making the distinction comes from trying to localize where the pain is coming from. Chronic orchialgia can be a part of CPPS, but there other symptomatology goes along with CPPS, including urinary symptoms. One of the most frequent symptoms reported with CPPS is perineal pain, specifically at the time of ejaculation, and there may also be pain at the tip of the penis, or suprapubic pain. There are also other findings in the evaluation. For example, high pelvic tone on a digital rectal exam is associated with CPPS, which is not necessarily an associated symptom found only with chronic orchialgia.

How prevalent is chronic orchialgia in the United States?

I think urologists in Europe have done a better job identifying the prevalence of chronic orchialgia than [urologists] in the U.S. In Europe, there is up to a 4.8% prevalence of chronic orchialgia, [whereas] there is not an exact percentage on the prevalence in the U.S. [However, it is estimated that] roughly 100,000 men come to a clinical environment for new evaluation for chronic orchialgia annually. It is a frequent clinical presentation that most urologists see week in and week out, even if it’s not their specialty.

What kind of clinical presentations do you commonly see?

There is a great deal of variability. The duration of pain can vary from 3 months to 20 to 30 years. The severity varies, [so] we always want to get a visual analogue pain scale to [determine the patient’s] pain level. It can vary from lower levels, such as a 2 [or] 3, in which pain is considered bothersome, to more severe levels like 9 to 10, where the pain is so [bad that] the patient can’t get off the couch or out of bed.

Distribution of the pain [should be] considered. Where is it localized? Where does it radiate? [And what is] the characterization of the pain? Is it a dull, heavy ache? Is it sharp? Are there associated symptoms? Within this 1 phrase of chronic orchialgia, there is a great variety of presentation and symptomatology.

Are there specific risk factors? What seem to be the associated conditions and etiologies?

I think one of the most important things we do as we are moving down the path of evaluation to treatment is identifying specific etiologies. A lot of what we call general chronic orchialgia is considered to have an unidentified etiology, so we look for specific etiologies in the history and on the physical examination. Do men have significant retraction of the testicle, and are they having to press the testicle back down? That can be a hyperactive cremaster muscle reflex. Is there a spermatocele that may have point tenderness to it? Is it epididymalgia versus orchialgia versus spermatic cord pain? Are there things in the [patient’s] history, such as inguinal hernia repairs, postvasectomy pain syndrome, other scrotal surgeries, or other pelvic surgeries that induced the pain? We want to rule out infectious etiologies, especially when there is high-risk behavior for sexually transmitted infections. We need to look at the man individually and, first and foremost, try to rule out specific etiologies that are easily treatable before we get into the more complex treatment algorithms.

If there is an infection, we are going to treat that. If there is a spermatocele with point tenderness, we have our diagnosis. If there is a varicocele with characteristic varicocele type pain, we are going to specifically target our treatment accordingly. In men that have undergone a complete evaluation—the history, physical examination, laboratory evaluation, imaging studies—and we have not been able to identify a specific etiology, we have data now showing that there is a neuropathic event that occurs in a lot of these men. We base that understanding on going backward from treatment to look at pathologic diagnosis. In 1978, Charles J. Devine Jr, MD, and Paul F. Schellhammer, MD, published the first paper on microsurgical denervation of the spermatic cord,

 which, if we look at the neuropathology, we have worked backward from treatment to pathology. In 2013, Sijo Parekattil, MD, et al identified what is known as the trifecta nerve complex

 that primarily reveals bundles of nerves that exhibit Wallerian degeneration, a reactive response to stimuli with increase in Schwann cells, and cytokines and a reactive response, which affected how the nerves appear micro anatomically. When he biopsied nerves in the spermatic cord of men with chronic orchialgia with or without identifiable specific etiologies, he found Wallerian degeneration in 3 nerve branches in 84% of them [compared with] 20% of the controls. The understanding of the pathophysiology has advanced leaps and bounds as we have gotten that microanatomical understanding, which has also allowed for targeted treatment.

What are the steps taken to evaluate a man who comes to the office with scrotal pain?

Like everything else in medicine, start with a thorough history and physical examination. The history is specifically targeted to the symptomatology: duration, pain characteristics, presence or absence of radiation of pain. Is there testicular retraction? Do they notice swelling that is worse when they have pain? Are there other associated symptoms that may indicate CPPS or other specific sources? Do they have a history of infections? Do they have a history of urolithiasis? If they have signs and symptoms of a distal ureteral stone, it is important to get a CT scan.

Moving on to the physical exam, [providers should] assess testicular volumes and evaluate for findings like varicoceles, spermatoceles, masses, and tumors. Specifically, can we reproduce the pain with palpation, and is there a retraction of the testis with Valsalva that’s significant? Further diagnostic evaluation [should then occur]. The key to the laboratory studies is the urinalysis, which helps to understand whether a urine culture [needs to be] reflexively [obtained] on that sample and, in specific scenarios where there seems to be higher risk, checking urine PCR for gonorrhea and chlamydia. I always obtain an imaging study in these men as well. I get a duplex Doppler ultrasound to look for findings that may be too subtle for our fingers to pick up on physical exam. Is there a potential for intratesticular intraedidymal masses that may be small enough that they are not palpable and are being masked by pain? Are there small spermatoceles that we may miss on exam that we can find with an ultrasound?

How is this condition treated, specifically in patients for whom a specific etiology cannot be identified?

For most of these patients, you are not the first doctor they’re seeing for this. They are frustrated. They are ready to get treatment. They want their quality of life back. The next most important step by most data involves assessing their response to treatment. First, in a patient who has newly diagnosed pain, we give a 3-month period of conservative therapy. Usually, that includes anti-inflammatories, scrotal elevation, and warm compresses/hot baths.

[If] they fail to respond, then we can categorize them as a [patient with] chronic orchialgia/chronic scrotal pain. We can talk [with] them about potential surgical intervention, [which is] only appropriate for men who have failed conservative treatment.

[If they fail] conservative treatment and there is not a specific etiology to target, the next important step is a spermatic cord block, [which] is done in the office. Typically, between 10 and 20 cc of bupivacaine is injected, and when I perform them, I try to target the areas where we know the Wallerian degeneration occurs in the spermatic cord—specifically, the cremaster muscle, the perivasal adventitious tissues, and the posterior lipomatous perivascular tissues behind the spermatic cord. The posterior one is a difficult place to target, but it also is where the least number of fibers of degeneration are typically found. I can at least target the cremaster nerves and the perivasal nerves with the spermatic cord block.

The spermatic cord block is not being performed as a therapeutic treatment [but rather] as a diagnostic test to categorize these men in their ability to respond to surgical therapy. Are they a good candidate for a microsurgical spermatic cord denervation? Study after study has reproduced that response to spermatic cord blocks helps predict success with surgical management, which is typically microsurgical spermatic cord denervation. The potential exception to that is that some men that have postvasectomy pain syndrome, with a specific physical exam finding of a boggy, congested epididymis with point tenderness. They may be appropriate candidates for microsurgical vasovasostomy or vasoepididymostomy, [which is] essentially a reconstructive vasectomy reversal [and] of course will reinstitute fertility, countering the reason they went through the vasectomy in the first place, but with some levels of success as well. We have to assess them appropriately.

What are the conservative treatment options to help manage neuropathic pain?

Medical therapy [can be used] to target nerve pain in these men. Some of the ones that have classically been used [include] tricyclic antidepressants, amitriptyline, and gabapentin. One being used more commonly is pregabalin [Lyrica]. We are seeing some level of success with medical therapies, but with the understanding that these are typically temporizing treatments; they are not necessarily curative. Treatment is potentially long term. Patients [can start] on these treatments, and [providers can] see their level of response, [which] may save the patient from surgery. We can try to titrate men off these medications and see how they do, but in many of them we are talking about chronic medical therapy.

How do you make the decision to move forward? Are there patients who prefer chronic medical therapy, and do you try to counsel them toward surgery?

The key is shared decision-making between the physician and the patient. In men with chronic orchialgia who have had specific etiologies ruled out, there is not something dangerous going on. They do not have a malignancy. They do not have an infection. There is nothing that is doing any damage to them per se. This is purely about their quality of life. Whatever achieves that level of quality of life that is acceptable for the individual is my goal and should be our goal as physicians. Whether that is medical or surgical management is going to come down to shared decision-making. For example, let’s say we put a patient on Lyrica or amitriptyline or gabapentin, and the patient says it has cut his pain score in half—he can go to work, he can do levels of workouts that he wants to, he does not have 0 pain, but it is temporized enough that he has regained the quality of life that he was after—[then] I think we achieved a great deal of the patient’s goal. We can continue that indefinitely unless things get worse [and] the patient becomes less responsive. [Additionally,] there are opportunities to give them holidays off treatment to see how they do, [but] we can reinitiate [treatment] if they relapse. In this situation, our goal needs to be the patient’s goal, which is different from when we are talking about organ-destroying processes, pathologies like oncologic processes, where we have to be extremely aggressive about treatment options in most situations. This is purely matching the patient’s quality-of-life desire.

Please discuss surgical approaches to treatment.

To give credit where credit is due, most of this comes from the work that Parekattil did identifying the trifecta nerve complex, and he went to a targeted denervation approach. When we think of microsurgical spermatic cord denervation, it is approached very much like a varicocele repair. That is why we see that a lot of orchialgia tends to fall in the hands of people who do a lot of varicocele repairs and microsurgery. A lot of fertility specialists are involved in treatment of chronic scrotal pain because that is kind of our neck of the woods. We can do the surgeries through a 1- to 1.5-cm transverse subinguinal incision, very minimally invasive with minimal recovery. We expose the spermatic cord, isolate it. We use operative microscopic visualization with magnification every time we do these, regardless of technique. The classic technique, described by Devine in the 1970s and refined by a lot of leaders in the field, has been a skeletonization technique where basically the spermatic cord is skeletonized and all the veins that are within the spermatic cord are ligated, except leaving a few of the defferential veins intact for drainage. The cremaster muscle is taken, and all visible microsurgical nerves are ligated and divided. Basically, you are left with a spermatic cord that only has components remaining including the arteries feeding the testicle blood microsurgically, lymphatic channels, and the vas deferens, if fertility is of interest. It is a very tenuous surgery. It is a meticulous technique, and it always makes us hold our breath when we are working around those crucial microscopic structures because we are picking everything else away from them.

With the understanding of the trifecta nerve complex Parekattil described, and when he started performing these targeted denervations, I took that technique and applied it to my patients. For years prior to that, I performed the microsurgical skeletonization, and then once we had a good understanding of this anatomic basis, I swapped over to the targeted denervation where we are ligating the neurovascular bundles in the cremaster muscle, the posterior lipomatous tissues, and then the perivasal adventitia, keeping in mind to maintain arterial vasculature. It cuts the surgery time in less than half, and we do not have to be as concerned about arterial flow to the testis and potentially injury to that or lymphatic channels. It allows us to maintain [most of] the spermatic cord as is, with much less tissue destruction to work through and a simpler, easier, faster surgery with less risk.

We have demonstrated that we get equivalent outcomes [and] had an opportunity to publish our data where we compared years of skeletonization technique versus changing to targeted denervation.

 When we get [a] patient who is responsive to the spermatic cord block, which does not necessarily mean they have 100% resolution of pain with block, as long as they have up to 50% improvement in the block, we expect good surgical outcomes with denervation, probably because it is very difficult to access that posterior lipomatous branch with the nerve block. In men with a good response to a spermatic cord block who undergo spermatic cord denervation, we see an approximately 70% chance of complete resolution of pain long term. [Additionally, there is a] 15% chance that they get significant improvement, which is defined as at least a 50% improvement from their preoperative visual analogue pain score to where they are postoperatively. Quite frankly, [that] leaves us with a 15% chance that all they are going to get is an incision and recovery and the pain is unchanged. But we always have to counsel them that there is a 15% chance of failure with this procedure. Most men are willing to take those odds with the potential that they are going to get the level of quality-of-life improvement that we can offer. Some options beyond denervation have been [examined] for when there is failure, but those are still preliminary.

Do you partner with other disciplines, such as pain management?

I think partnering with other specialties and making this a multidisciplinary approach is crucial. One of the things that we suggest, especially in the men that have some component of CPPS, is consideration of pelvic floor physical therapy. This can even [offer] improvement in [patients with] chronic orchialgia without CPPS, with targeted techniques in the inguinal region and in the scrotum. I’ve seen a lot of patients [achieve] some level of success. Does that usually mean long-term resolution? Typically not. But if they are looking for some level of response—maybe in the [men] that have lower pain scores—and are willing to have repeat therapy visits, they can achieve some level of benefit.

Our pain management colleagues are important resources for us to pair with to approach these patients. [For] every patient that walks in my door for chronic orchialgia, [I offer] the opportunity [to consult] with pain management specialists, even before performing the cord block. Because if we are talking about options, there are [men] for whom the last thing they want is a surgical approach. My colleagues in pain management are going to be much better equipped and versed in medical therapy for these chronic pain syndromes than I am as a urologist.

Is there anything you feel our readers should know?

I would add that it is good for the clinician to be aware of the importance of differentiating the men that have a hyperactive cremaster muscle reflex as the source of their orchialgia. [This] may take a whole different surgical approach, which is a simpler procedure than spermatic cord denervations, varicocele repairs, things that a lot of the microsurgeons do [often]. In men that have a retractile testicle, that is really the key to their pain. [Important] questions to ask those men: “Do you get the severity of retraction that you have to push the testicle back down into the scrotum? And do you have pain at times other than times of retraction?” For men with orchialgia secondary to testicular retraction [because of] a hyperactive cremaster muscle reflex, we can offer a similar approach through a subinguinal microsurgical technique through that small incision and simply circumferentially release the cremaster muscle. We can eliminate the retraction, which is more effective than an orchiopexy. I recently published a study looking at that, and we had a great deal of success in our patients.

 That’s a simple, straightforward procedure that any urologist can perform. The success rates are exceptionally high, and you will get a satisfied patient.

 Devine CF Jr, Schellhammer PF. The use of microsurgical denervation of the spermatic cord for orchialgia. 

 Parekattil SJ, Gudeloglu A, Brahmbhatt JV, Priola KB, Vieweg J, Allan RW. Trifecta nerve complex: potential anatomical basis for microsurgical denervation of the spermatic cord for chronic orchialgia. 

2013;190(1):265-270. doi:10.1016/j.juro.2013.01.045

 Kavoussi PK. Validation of targeted microsurgical spermatic cord denervation: comparison of outcomes to traditional complete microsurgical spermatic cord denervation. 

2019;21(4):319-323. doi:10.4103/aja.aja_87_18

 Kavoussi PK. Microsurgical subinguinal cremaster muscle release for chronic orchialgia secondary to hyperactive cremaster muscle reflex in adults. 

 2020;52(1):e13493. doi:10.1111/and.13493

Articles

In this interview, Parviz K. Kavoussi, MD, discusses his diagnostic work-up for patients who present with chronic testicular pain and describes conservative and surgical management approaches for the condition. 

Chronic orchialgia: How to diagnose and treat the challenging condition

Editorial Council, is professor of urology at Johns Hopkins University School of Medicine, Baltimore, Maryland.

The reports of clinical trial results for 2 novel oral testosterone undeconoate agents for use as testosterone replacement therapy bring forward a major advance in the management of testosterone deficiency. The introduction of these agents represents a paradigm shift in this clinical space for sexual medicine practice (see articles, pages 6-7).

Historically, an oral option for testosterone replacement therapy was unavailable because of risks of liver toxicity, including cholestasis and jaundice, associated with earlier developed 17-alpha-alkylated oral analogues. A host of testosterone delivery routes including transdermal (gels, creams, or patches), buccal, intranasal, intramuscular, and subcutaneous options have been in use, but each preparation has potential limitations and all are more onerous to administer than the simple mode of oral treatment.

These novel oral agents offer a new entry to the testosterone replacement therapy armamentarium by addressing the liver toxicity issue. They feature specialized formulations that avoid adverse hepatic effects. In clinical trials, both oral agents were found to produce no significant adverse effects on liver function tests. Rather, there is evidence reportedly of improved markers of liver disease.

The rigorous study and promising clinical availability of oral therapy for testosterone deficiency are flash points in the current era, in which the utility of testosterone therapy is under critical review. Recent concern regarding the proper indications for testosterone replacement therapy has prompted regulatory agency requirements and medical society recommendations to assist practitioners in clinical practice. A simpler oral treatment for testosterone deficiency presents another variable to be fully defined in exercising its appropriate prescription and use.

These trials provide early reassurance of safety, although ongoing studies may further elucidate safety aspects across cardiovascular, hematologic, and genitourinary systems of regular clinical concern associated with testosterone replacement therapy. It will also be valuable to investigate further the efficacy of oral therapies across conditions of testosterone deficiency, including adult-onset hypogonadism-related diabetes mellitus, testicular dysfunction as a complication of prior radiation or chemotherapy, HIV infection status, and other conditions characterized by low testosterone function.

The new oral therapies are a welcome advance for managing testosterone deficiency and will certainly prompt thorough review and positioning in process-of-care therapeutic algorithms. Assuredly, current guidance for evaluation and monitoring schemes for testosterone replacement therapy will remain operable. Recommendations for lifestyle modifications to improve health outcomes, which may then modify the role for testosterone interventions, should remain in force.

An ongoing limitation of exogenous testosterone therapy having potential adverse effects on normal spermatogenesis that compromises fertility remains relevant with use of oral therapies. This latter concern underscores the purpose of ongoing studies in men’s health to foster interventions that normalize male andrologic function and optimize natural wellness.

"The rigorous study and promising clinical availability of oral therapy for testosterone deficiency are flash points in the current era, in which the utility of testosterone therapy is under critical review," writes Arthur L. Burnett II, MD, MBA.

Oral testosterone agents mark important paradigm shift

 Editorial Council, is professor of urology at Johns Hopkins School of Medicine, Baltimore.

The current COVID-19 viral pandemic has upended all of our lives, both personally and professionally. Because of it, we are enduring a sobering new reality with its threat to health and life.

I suspect the communications from many of my colleagues on the 

editorial board will echo similar sentiments of a constructive call to action, messages of collective sacrifice, and unity of purpose. Given that our medical profession as urologists is not commonly centered on emergent or intensive care matters, unlike that of so many of our clinician colleagues, we recognize that much of our craft is not as urgent in these times as for others. Our responsibility has been to participate rightly in medical triage efforts, therefore deferring “non-essential” surgeries and clinical activities.

Urology APPs: Making an impact during the COVID-19 pandemic

Willing as we are to prioritize the management of urologic conditions that truly rate as having urgency or high mortality risk, this new reality has nonetheless impacted our professional practices organizationally and economically. As for all business concerns at this time, the economic slowdown affects the livelihood of health care providers, urologists included. The American Medical Association has acknowledged that the pandemic has harmed the practices of health care providers universally, and the crisis presents costs of treating COVID-19-positive patients as well as sustaining revenue losses with costs for payroll and overhead. As urologists, we will have to adjust in terms of what we clinically manage but also how we will do it and how we will finance it.

Undoubtedly, we will be challenged by the circumstances of this pandemic. Our response may well be to adapt to fill positions that are unfamiliar and possibly unappealing. For many of us, we will repurpose in new enterprises, new business models, and new opportunities for work productivity and life utility. We will be resilient.

Some areas of urology will be impacted considerably more than others. In these times of resource conservation, benign and quality of life conditions, and subspecialty concerns in urology may be perceived to be less serious or life threatening than malignancies or conditions risking loss of an organ. Such non-urgent conditions would aptly be relegated for management sometime in the future.

Sexual medicine conditions are predictably included in the category of conditions whose management may well be deferred. These conditions include erectile dysfunction, Peyronie’s disease, and testosterone deficiency. Penile prosthesis surgery, surgical reconstruction of the genitalia, and other surgical procedures in sexual medicine conceivably are deemed “non-essential” and are being rescheduled.

On the other hand, sexual medicine issues remain active and can be readily met with newfound telehealth consultation practices. Whether the need for sexual interactions is heightened or reduced in these times in which social distancing is practiced remains an open question.

How to code for urologic care during the COVID-19 pandemic

Specialty organizations in sexual medicine are grappling with canceled professional meetings as much as institutions are wrestling with limited in-person training exercises. This reality is the same for all professional organizations and institutions currently. The value of new science and training in sexual medicine and elsewhere is recognized, and educational programing must continue.

Thankfully, we are in an age of remote electronic learning. Using various media to promote discovery and learning offers a new way of life. Look for “virtual” conferences and training sections focused on sexual medicine that will be vital for progress in our profession and service to our patients.

"For many of us, we will repurpose in new enterprises, new business models, and new opportunities for work productivity and life utility. We will be resilient," writes Arthur L. Burnett, II, MD, MBA.

Pandemic brings new challenges, opportunities-and resilience

 Editorial Council, is professor of urology at Johns Hopkins University School of Medicine, Baltimore.

The research by Gross et al provides important grounds for reconceptualizing infectious complications associated with penile prosthesis surgery (see 

"Data reveal timeline of post-IPP infections").

 The observations that penile prosthesis surgical infections occurring early are frequently associated with anaerobic bacterial organisms and that these infections overall comprise diverse pathogens including fungal organisms fundamentally alter conventional thinking related to this topic area.

Previous thinking considered primarily gram-positive bacterial organisms with antibiotic coverage directed accordingly. Prosthetic surgeons may wish to consider this new information strongly in applying revised antimicrobial protocols for penile prosthesis surgery.

Although prosthetic device infection is an infrequently occurring complication of prosthetic surgery in modern times, it is generally recognized that it represents the most serious complication risk of this surgery. Device loss (removal) and penile tissue damage are common sequelae of this complication. It is acknowledged that in the acute setting, salvage approaches such as the Mulcahy procedure have been used successfully under select indications.

In accordance with clinical guidelines, surgeons are advised to inform patients about the potential risk of device infection associated with this procedure. To mitigate this risk, good practice is to administer antibiotics perioperatively despite the rigor of deferring surgery in the presence of active clinical infection and performing the surgery with meticulous technique.

No consensus position exists as to the established antimicrobial regimen to be used for penile prosthetic surgery. Antibiotic regimens standardly feature a gram-positive-directed antimicrobial agent such as vancomycin or a cephalosporin, in combination with a gram-negative-directed antimicrobial agent such as an aminoglycoside. Expanded coverage to include agents directed toward anaerobic and fungal organisms warrants consideration given today’s paradigm shift.

It is accepted that this report may not represent a definitive organism profile registry, although the large multi-institutional effort here is commendable. It is acknowledged as well that only a rigorous comparative study of antimicrobial agents and regimens may affirm the optimal infectious disease approach. However, such a future study is unlikely to be probative given the low frequency of prosthetic device infection. Ongoing science of prosthetic infections including biofilm microbiology may also be advantageous to advance strategies to counteract infection risk.

"The observations that penile prosthesis surgical infections occurring early are frequently associated with anaerobic bacterial organisms and that these infections overall comprise diverse pathogens including fungal organisms fundamentally alter conventional thinking related to this topic area," writes Arthur L. Burnett, II, MD, MBA.

Arthur L. Burnett, II, MD, MBA

Articles

Chronic orchialgia: How to diagnose and treat the challenging condition

Oral testosterone agents mark important paradigm shift

Pandemic brings new challenges, opportunities-and resilience

Post-prosthesis infection data alter conventional thinking