37 Senthy Sellaturay1, Kamran Ahmed1,2, Muhammad Shamim Khan1,2,3, and Majed Shabbir1 1 Department of Urology, Guy’s & St. Thomas’ Hospital, NHS Foundation Trust, London, UK 2 MRC Centre for Transplantation, King’s College London, King’s Health Partners, London, UK 3 Guy’s & St. Thomas’ Hospital, NHS Foundation Trust, King’s College, London, UK Scrotal pathology is commonly encountered by the urologist. Problems range from acute presentations due to trauma, torsion, or acute infection to chronic inflammatory conditions with chronic pain which can be difficult to manage. This chapter addresses the management of testicular trauma and inflammatory conditions relating to the testis. Various types of testicular trauma including testicular rupture, haematoceles, testicular dislocation, and cord disruption are reviewed. The role of radiological imaging is explored along with treatment strategies. The second half of this chapter is dedicated to reviewing acute and chronic inflammatory conditions affecting the testis. Investigations and treatment of acute bacterial and viral orchitis are examined, as well as complications thereof. The different types of chronic inflammatory conditions are reviewed, as are the range of conservative, medical, and surgical treatments which will provide the clinician with a strategy for these difficult conditions. Keywords testis; trauma; infection; inflammation; orchitis; epididymitis Scrotal trauma may either be blunt or penetrating. Blunt injuries arise from direct blows or straddle injuries and account for nearly 85% of testicular injuries [1]. Penetrating trauma is less common and includes stab wounds or gunshot injuries. When considering blunt scrotal trauma, it is important to appreciate the mechanism and force of injury and to consider the risk of collateral damage. The testis can withstand approximately 50 kg of blunt trauma before the tunica albuginea ruptures [2]. If the injury is sustained with a fall astride pattern, the urethra can also be injured. Typically, blunt scrotal traumas are unilateral injuries. Conversely, penetrating injuries are more likely to be bilateral, especially when related to gunshot wounds (i.e. bilateral damage in approximately 1% after blunt injury, compared to 30% with penetrating injuries). Gunshot wounds from low‐velocity handguns (up to 300 m s−1) cause less trauma than high‐velocity rifles (up to 1000 m s−1). It is important to appreciate that the blast effect may cause more tissue damage than is evident initially, and such wounds will often be contaminated with debris. Depending on the severity, there are varying manifestations from trauma, including subcutaneous haematoma, hydrocele, haematocele, testicular dislocation, fracture, or rupture. Trauma‐induced testicular torsion is also a well‐recognised entity, with a reported incidence of 4–8% in most studies [3]. Scrotal trauma may also result in injury to the epididymis including contusion, haematoma, rupture or fracture, whilst injuries to the spermatic cord can involve damage or transection of the vas deferens and vascular structures. Presentation is invariably with acute pain, usually with significant scrotal swelling and visible bruising. Delayed presentations may be further complicated with local or systemic signs of infection. Marked scrotal swelling can make accurate clinical assessment of the scrotal contents difficult, and ultrasound should be used as the first‐line investigation. Ultrasound should be considered an extension of the clinical assessment of the scrotum [4]. It can be effectively used to assess the integrity and vascularity of the testes and can distinguish testis rupture from other injuries such as haematocele, hydrocele, torsion, and epididymal injury. The seminiferous tubules have a homogenous appearance on ultrasound and alteration of the normal uniform echo pattern to reveal heterogeneity in the echotexture of the testis following trauma suggests testicular rupture or intratesticular haematoma [5]. Disruption in integrity of the tunica albuginea is highly suspicious of a testicular rupture [6]. Ultrasound has been reported as having a specificity of 75–98% and sensitivity of 64% for detecting testicular rupture following trauma [1, 7] Magnetic resonance imaging (MRI) may be useful in equivocal cases of rupture, but due to expense and length of time required to perform the examination, it is not widely used [8]. Testicular rupture is said to have occurred when the tunica albuginea is disrupted. Therefore, surgical exploration should be undertaken in all cases of testicular rupture [9]. Early exploration can improve testicular salvage when exploration is conducted within 72 hours of trauma [1, 10]. Patients must be warned of the possible need for orchidectomy if the testis cannot be salvaged. Conservative management of significant blunt scrotal trauma is associated with greater risk of infection, testicular atrophy, and orchiectomy. The principles of surgery are to evacuate any haematoma, debride any extruded and nonviable seminiferous tubules, and close the tunica albuginea (Figure 37.1). Any testicular tissue, which is potentially viable, should be salvaged if at all possible for endocrine function as well as for psychological reasons. Postoperatively, a drain is left in situ for the first 24 hours and broad‐spectrum antibiotics given. The patient should be managed with a scrotal support in the immediate postoperative period. Figure 37.1 To prevent testicular atrophy occurring from pressure by the haematoma, the testicle should be explored, the blood clot evacuated, and the tear in the tunica albuginea repaired. In cases where the tunica albuginea cannot be easily closed without tension, but the seminiferous tubules look viable, a vascularised tunica vaginalis flap can be used to close over the tunica albuginea defect in a double‐breasted manner [11]. It is important not to close the tunical albuginea in a situation where the underlying tubules will be under pressure, which will result in testicular damage with subsequent tubular dysfunction. A haematocele is bleeding confined to the tunica vaginalis, whereas in haematomas, the blood extends beyond the tunica vaginalis and extrudes into the layers of the scrotum. A haematocele may accompany testicular rupture. Large and tense haematoceles often necessitate early exploration due to the significant pain and discomfort, and more importantly the testes may be under high pressure leading to ischaemia, necrosis, and testicular atrophy. Exploration allows evacuation of the clot, relieving symptoms of pain and risk of infection. Conservative management of smaller, stable scrotal haematomas, hydroceles, and contusions is achieved with ice, rest, and elevation [9]. Testicular dislocation is rare, and the testis may be found in the inguinal canal or abdominal cavity. This may be repositioned manually primarily and will require subsequent orchidopexy. In cases of cord disruption seen with penetrating injuries, the testis may be salvaged with cord realignment if detected early. The primary realignment should aim to re‐establish the vascular supply microsurgically. A subsequent staged microsurgical vaso‐vasostomy can be performed at a later date if the testis remains viable and functional. Inflammation of the testicle may involve the testis, epididymis, or both. Most inflammation of the epididymis will eventually involve the testis. The epididymis is relatively soft and when inflamed it expands to form a tender mass behind the testis. The rigid tunica albuginea cannot expand, and the increased pressure inside the tunica may cause ischaemia of the testis. Inflammation in either testis or epididymis will lead to a secondary hydrocele as is seen with free fluid in the peritoneal cavity from peritonitis. Mumps and other viruses can cause an acute orchitis, which is sometimes bilateral. Worldwide, 290 cases per year per 100 000 population were diagnosed between 1977 and 1985 [12]. There has been a dramatic reduction in the incidence of mumps since the introduction of the measles‐mumps‐rubella (MMR) vaccine. Recently there has been an increase in the incidence of mumps [13], mainly in adolescents; this has occurred for two reasons: 20 years ago there was a shortage of the MMR vaccine and a measles‐rubella vaccine was used instead, and there were links between the MMR vaccine and autism spectrum disorders, which caused a reduction in the uptake of the MMR vaccine. Subsequent reviews have shown that no such link exists [14]. Mumps usually present with a prodromal illness associated with unilateral or bilateral parotid swelling. Mumps orchitis is the most common complication in adolescent pubertal males, and testicular swelling occurs 10 days after the onset of parotitis. It occurs in 15–40% cases, and it can be unilateral or bilateral. Diagnosis is usually made on history of exposure, although real‐time polymerase chain reaction (RT‐PCR) is a good sensitive diagnostic technique [15]. Virus‐specific IgM antibody can be measured using direct or indirect enzyme‐linked immunosorbent assay (ELISA) techniques, though the sensitivity is variable [13]. Generally, most cases are diagnosed with normal white blood cell count, raised C‐reactive protein, negative urine analysis, and midstream urine sample. Ultrasound shows diffuse hypervascularity and enlargement of the testes and epididymis. Treatment is essentially supportive because the mumps virus is usually self‐limiting. Supportive measures include bed rest, scrotal support, and analgesia and anti‐inflammatories along with broad‐spectrum antibiotics where bacterial infection cannot be excluded. The role of steroids has been controversial. While effective at reducing pain and swelling, its role in preserving fertility is uncertain. Likewise, mixed reports exist on the benefit of interferon‐α 2B in such cases [16]. Complete infertility is a rare complication, but subfertility occurs in an estimated 13% of patients. In cases where azoospermia does develop, sperm may still be retrieved microsurgically for use in assisted conception. Testicular atrophy can occur in up to 30–50% of affected testes [17]. Many other viruses can also cause acute viral orchitis: Coxsackie [18], infectious mononucleosis [19], hepatitis B [20], herpes virus 2 [21], bat salivary gland virus, and dengue [22]. Epididymo‐orchitis is inflammation of both the epididymis and testes. Infection usually begins in the epididymal tail, before spreading to the rest of the epididymis and into the testis. It is usually unilateral, but in cases of severe infection may become bilateral. The source of infection is primarily urethralA but can also be haematogenic. The majority of cases in sexually active males younger than 35 years of age are due to sexually transmitted infections (STIs) such as chlamydia (more commonly) or gonorrhoea. In older patients, it is usually due to common urinary pathogens such as Escherichia Coli and can arise as a complication of urethral instrumentation or catherisation or as a result of prostatic obstruction complications [23, 24]. Acute epididymitis was so common after urological operations that 50 years ago vasectomy was always performed before prostatectomy. This has generally been replaced by using effective antibiotic prophylaxis. However, a ‘chemical epididymitis’ is still reported after selected endoscopic cases such as transurethral resection of the ejaculatory duct (TURED), due to reflux of noninfected urine through the urethra into the open resected ejaculatory ducts of the prostate [25, 26]. Bacterial orchitis can also occur from haematogenous spread, where it forms a lump, which may resemble a tumour. In certain cases of bacterial epididymo‐orchitis due to a urinary pathogen, urological investigations may be required to exclude any anatomical or functional abnormality. In such cases, a flow rate, postvoid residual ultrasound, and cystoscopy may prove useful. Characteristically patients present with rapid onset scrotal pain, which is usually unilateral. There may be symptoms of urethral discharge, urinary tract infection (UTI), or prior history of bacteriuria. At first there is a painful swelling, involving the epididymis, but development of a secondary hydrocele, erythema, and oedema of the scrotum and extreme tenderness can make it impossible to distinguish testis from epididymis. In severe cases, the changes may be bilateral and associated with local abscess formation, especially in those who are more susceptible to infection (patients with diabetes or are immunocompromised or elderly). Patients may also describe fever, shivers, or rigours, depending on severity. The primary aim is to isolate the infective cause to confirm the diagnosis and to guide antibiotic therapy. A midstream urine sample should be sent for microscopy and culture. In those who are sexually active, a urethral swab should be taken. Gram staining of a urethral smear (≥ 5 polymorphonuclear leucocytes [PMNLs] per high power field × 1000) or Gram‐stained preparation from a centrifuged sample of first passed urine (FPU) (≥ 10 PMNLs per high power field × 1000) should be performed. The presence of gram‐negative intracellular diplococci suggests Neisseria gonorrhoea. A urethral swab should be sent for N. gonorrhoeae culture and FPU or urethral swab for nucleic acid amplification test (NAAT) for N. gonorrhoeae and Chlamydia trachomatis [27, 28]. It is important that the urethral swab is not taken within two hours of passing urine because this can decrease the sensitivity of the test. Patients with an infection suspicious of a STI should be screened in a sexual health clinic to exclude any other concurrent sexual health infection and have contact tracing. Additional investigations should include a Doppler ultrasound to confirm the presence of inflammatory changes in the epididymis and testis. Blood tests to confirm a raised white cell count and inflammatory markers (i.e. C‐reactive protein) are useful. In cases of systemic infection, a blood culture should also be performed. The key condition to differentiate in cases of acute testicular pain and swelling is testicular torsion. Torsion is a surgical emergency and rapid restoration of flow to the testis should happen within six hours to allow the best chance of testicular salvage [29]. Torsion is more common in young men (< 20 years) but can occur at any age. A lack of definitive clinical findings often leads to misdiagnosis, with the most common incorrect diagnosis being epididymo‐orchitis. Ultrasound and Doppler scanning are not completely reliable at excluding torsion and may miss torsions in cases of low‐level twists (< 360°), in children, and in cases of intermittent torsion. If torsion cannot be safely ruled out clinically, then scrotal exploration must be undertaken, and ultrasound should not delay intervention [30–33]. Acute idiopathic scrotal oedema may affect the scrotum [34, 35], particularly in young boys, and torsion must again be excluded. A similar appearance is seen in children with fat necrosis, giving rise to an inflammation of the scrotum, and if correctly diagnosed, can be treated conservatively [36]. Other differentials include trauma, testicular tumours, and torsion of the testicular appendage. Systemic antibiotic therapy is the mainstay of treatment and should be managed in conjunction with local microbiological advice. In men younger than 35 years of age, where a STI is the likely underlying cause, a fluoroquinolone such as ofloxacin combined with doxycycline will cover chlamydial and gonococcal infections. In older men where the most likely pathogen is a gram‐negative bacilli, with E. coli being the most common, then treatment again with a fluoroquinolone such as ofloxacin is the best first line due to its excellent testicular tissue penetration. Treatment should continue for 14 days; bed rest and analgesia are suggested as required. Anti‐inflammatories and a scrotal support can provide additional relief. Patients should be seen after two weeks to ensure an adequate response to treatment, and persistent changes with a failure to respond to the correct antibiotic regime raises the possibility of a tumour mimicking the initial presentation. An abscess may form a fluctuating swelling which discharges pus. This will require urgent incision and drainage. Acute infection can also give rise to chronic pain, infertility, and testicular infarction. Infarction will require subsequent orchiectomy. There is little written in the literature on chronic epididymitis, and the incidence and natural history of the disease are not truly known and poorly understood. Nickel proposed a definition for chronic epididymitis: ‘symptoms of discomfort and/or pain at least three months in duration in the scrotum, testicle, or epididymis, localised to one or each epididymis on clinical examination’ [37]. The aetiology of the condition is thought to be infectious, inflammatory, or obstructive, with many cases having no identifiable cause noted. Tuberculous epididymitis may have a surprisingly acute onset and should also be considered in cases of acute epididymitis where no other bacterial pathogen is found. Tuberculous epididymitis can be the sole presentation of genitourinary tuberculosis. The more common situation of urine‐borne infection travels along the vas deferens to the cauda epididymis and can be difficult to diagnose in the absence of renal involvement [38]. Blood‐borne tubercle bacilli may lodge in the caput epididymis to form a tuberculoma [39]. In either situation, there may be an acute inflammatory response, which is followed by a chronic phase in which the caseating tuberculoma of the epididymis forms a chain of bead‐like swellings continuing up the vas and involving the seminal vesicle. Tuberculous epididymitis may be seen in patients from countries where tuberculosis (TB) is prevalent, those who have had TB previously or are immunocompromised. Three early morning urine samples should be sent for acid‐fast bacilli stained with Ziehl‐Neelsen stain and cultured on Lownstein‐Jensen medium. Polymerase chain reaction of urine can also detect the bacterium. A small abscess may point to the skin of the scrotum and breakdown to form a sinus from which tubercle bacilli may be recovered. When there is no evidence of TB elsewhere in the urinary tract, the diagnosis is difficult and may require a biopsy. Modern treatment for TB is effective with standard combination of anti‐TB drug: isoniazid, rifampicin, ethambutol, and pyrazinamide. When only the epididymis is involved, it may be removed, but often the testicle is also involved, making an orchidectomy necessary. In cases of recurrent epididymitis, when the source of infection is clearly from the urinary tract, it may help to stop the succession of attacks by dividing the vasa. Unfortunately, this is not always successful; even after vasectomy, the inflammation of the epididymis may grumble on and require epididymectomy. In the postvasectomy setting, extravasation of spermatozoa into the epididymis can provoke a chronic granuloma with features suggestive of TB, probably because the acid‐fast helmet of the spermatozoon – the galea capitis – is antigenically similar to the envelope of the tubercle bacillus [40]. Around these acid‐fast particles, there are foreign body giant cells and macrophages but no caseation. Granulomatous epididymitis has also been described following intravesical bacillus Calmette‐Guérin therapy [41]. The seminal granuloma is different from chronic granuloma in the testis, which follows repeated urinary infections. It forms a firm mass in the testicle, which cannot be distinguished from cancer and requires orchidectomy. Histologically, there is chronic inflammatory tissue and fibrosis [42, 43]. Chronic granulomatous inflammation of the vas and testicle can be caused by infection with Schistosoma. The vas deferens and seminal vesicles may be outlined in the plain abdominal X‐ray with thin lines of calcification. Inflammation of the testis is complicated by vascular obstruction by the worms and ova leading to ischaemia as part of the pathological process [44]. The mass may be indistinguishable from a tumour [45–47]. Gonadal schistosomiasis is exceptionally rare but should be considered in areas where Schistosomiasis is endemic [48]. This can arise as a rare but reported consequence of candidal urine infection. Patients who are immunosuppressed pare particularly at risk, as are those with indwelling catheters. Changes can be unilateral or bilateral and can develop over months. Such cases are may be complicated with local abscess formation, requiring drainage, or in advanced cases, orchidectomy. If detected early, patients may respond to oral anti‐fungal medicines, such as fluconazole, for up to six weeks [49]. Malacoplakia is a chronic granuloma in which histiocytes contain specific calcified and laminated microspheres, the Michaelis–Guttmann bodies. In the testicle, it gives rise to a hard mass indistinguishable from cancer [50–52]. Actinomycosis of the testicle produces a complex of sinuses leading down to the chronically inflamed mass. The characteristic ‘sulphur grains’ formed by the fungal mycelia may help in the diagnosis of this exceptionally rare disease. The treatment is orchidectomy along with all the sinuses under tetracycline cover [53]. Brucellosis is equally rare, except in the Middle East. Approximately 1 in 10 men with brucellosis may develop epididymo‐orchitis. It forms a hard mass in the testicle, and only when the testicle has been removed on suspicion of cancer is the diagnosis questioned, and then confirmed by immunological tests [54–56]. Up to 6% of patients with Behçet disease have involvement of the epididymis [57]. Gumma of the testis was common during the nineteenth‐century epidemic of syphilis and much was made of the clinical distinction between gumma and cancer. Syphilis has shown resurgence of late, and testicular gumma is still reported. It is impossible to distinguish from cancer, and as a consequence, it is often confirmed only after orchiectomy [58]. In a recent reported case, a patient presented with a penile and testicular gumma. Although the ultrasound was unable to exclude tumour, the patient was treated conservatively with four weeks of antibiotics due to the positive syphilis serology (doxycycline as penicillin allergic). He responded well and the follow‐up scan showed complete resolution of the lesion by 10 months. This is the only reported case of conservative management of a testicular gumma [59]. These include coccidioidomycosis [60], cytomegalovirus [61] (after immunosuppression), sarcoidosis [62, 63], and filariasis, which causes acute inflammation at first before it goes on to elephantiasis of the scrotum and hydrocele with a chronic granuloma in the testicle. Perhaps the rarest of all causes of epididymitis is leprosy [64]. Drug‐induced epididymitis (e.g. amiodarone) is also a well‐recognised entity and cessation of the drug and switching to an alternative anti‐arrhythmic medication is usually sufficient [65]. Reassuring patients is often the most important part of management. Armed with the knowledge that there is nothing sinister, patients are more able to manage their symptoms effectively. A scrotal support, simple analgesia, local heat therapies, and avoiding aggravating activities may also be helpful. There is no clearly definitive method of treating chronic epididymitis. Symptomatic control of the ensuing pain and discomfort forms the mainstay of medical therapy. Strategies include anti‐inflammatory agents, anxiolytics, narcotic analgesics, and injection therapy with steroid or anaesthetic in the form of cord blocks, all with variable success. The poor response to such approaches often results in the need for a surgical approach by epididymectomy. Epididymectomy may have a role to play in carefully selected cases. This can be an effective strategy in the rare situation where inflammatory changes are solely localised to the epididymis. The surgery is performed through a midline scrotal incision. The cord is identified and the vas traced down to the epididymis. The epididymis is separated at the hilum of the testis. Bipolar diathermy should be used to achieve haemostasis, with special care needed when dissecting at head of the epididymis. The blood supply to the epididymis comes from a small branch of the testicular artery near the caput epididymis (Figure 37.2). It is important to secure this vessel without injuring the main artery of the testis (Figure 37.3). By pulling the epididymal head laterally, the main testicular artery can be preserved. Figure 37.2 Epididymectomy: a little branch of the testicular artery supplies the epididymis. Figure 37.3 Epididymectomy: the epididymis is removed, sparing the main testicular artery. There is limited clinical data with regards to epididymectomy, with most data available reporting on surgery for post vasectomy pain. Mittemeyer’s study [24] showed that out of 89 patients identified with chronic or recurrent epididymitis, 61 patients underwent epididymectomy and eventually returned to active duty. Davis et al. reported on 45 patients seen with chronic unilateral or bilateral orchialgia [66]. Orchidectomies were performed with the inguinal approach achieving 73% complete relief of pain and the scrotal route attaining 55% complete relief of pain. Epididymectomies were less successful with the majority of patients proceeding to have an orchidectomy. They concluded that inguinal orchiectomy was the procedure of choice for the management of chronic testicular pain when conservative measures were unsuccessful. However, post‐vasectomy, chronic pain has been shown to be cured in 50% of patients with simple epididymectomy [67] and reported patient satisfaction as high as 43% following epididymectomy for chronic epididymitis [68]. The benefit from epididymectomy for postvasectomy pain has also shown to be long‐lasting when patients have been reviewed at five years [69]. Epididymectomy for postvasectomy pain has been shown to be more successful than epididymectomy performed for other nonvasectomy causes with 93% of patients having less or no pain postoperatively compared to 75%, respectively [70]. Therefore, with good patient satisfaction and a favourable long‐term outcome, epididymectomy appears to be an effective treatment option particularly for post‐vasectomy chronic epididymal pain which cannot be managed conservatively. Calleary [71] suggested that epididymectomy for structural abnormalities had excellent results, but for those with chronic pain a 55% chance of improvement at best was achievable; therefore, this group should be counselled about the low risk of success. It is important when counselling such patients that the surgery may not improve their pain, especially because this is the sole symptom they wish to be free from. From our experience, patients with localised structural changes and tenderness which isolates specifically to the epididymis are those most likely to benefit from its removal. In those where the pain is more diffuse, or not accompanied with structural epididymal change, the outcome is less assured, and alternative strategies should be considered. In those with diffuse pain who respond well to cord blocks, a microsurgical cord denervation can provide more effective symptomatic relief [72, 73].
Testes Trauma and Inflammation
Abstract
37.1 Testicular Trauma
37.1.1 Investigations
37.1.2 Management
37.1.2.1 Testicular Rupture
37.1.2.2 Haematocele
37.1.2.3 Testicular Dislocation
37.1.2.4 Cord Disruption
37.2 Inflammatory Diseases of the Testicle
37.2.1 Acute Inflammation
37.2.1.1 Viral Orchitis
37.2.1.2 Bacterial Epididymo‐orchitis / Orchitis
37.2.2 Clinical Features
37.2.3 Investigations
37.2.4 Differential Diagnosis
37.2.4.1 Testicular Torsion
37.2.4.2 Idiopathic Scrotal Oedema
37.2.5 Treatment
37.2.6 Complications
37.3 Chronic Inflammation
37.3.1 Tuberculous Epididymitis
37.3.1.1 Complications
37.3.2 Granulomatous Epididymitis
37.3.3 Granulomatous Orchitis
37.3.4 Bilharzial Epididymitis
37.3.5 Candidial Epididymo‐Orchitis
37.3.6 Malacoplakia
37.3.7 Actinomycosis
37.3.8 Brucellosis
37.3.9 Behçet’s Disease
37.3.10 Syphilis
37.3.11 Other Causes of Epididymo‐Orchitis
37.4 Treatment
37.4.1 Conservative Therapy
37.4.2 Medical Therapy
37.4.3 Surgical Therapy
37.4.3.1 Epididymectomy
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