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chapter 132

Abnormalities of the Testis and Scrotum and Their Surgical ManagementJulia Spencer Barthold, MD

Embryology of Testicular Development and Descent

Cryptorchidism (Undescended Testis)

Varicocele

Hernias and Hydroceles

Acute Scrotum

Epididymal, Vasal, and Scrotal Anomalies

Developmental abnormalities of the testis and inguinoscro-tal region, including cryptorchidism, varicocele, hernia/hydrocele, and torsion of the spermatic cord or testicular

appendages comprise some of the most common anomalies seen in male children. Despite their frequency, relatively little is known of the underlying factors contributing to the pathogenesis of these diseases. All may be associated with significant short- or long-term morbidity. Moreover, their clinical presentation may overlap and at times present diagnostic challenges. Our ability to define the degree to which cryptorchidism and varicocele affect global tes-ticular function in individual patients remains limited. Therefore management options remain controversial in part because of dif-ficulty correlating early childhood therapies with long-term repro-ductive outcomes.

EMBRYOLOGY OF TESTICULAR DEVELOPMENT AND DESCENT

Testicular DevelopmentThe human gonadal ridge containing somatic and germ cells is first identified on the medial urogenital ridge at 32 days after ovulation and is indistinguishable between males and females (Hanley et al, 1999). Primordial germ cells migrate from the yolk sac and differentiate into gonocytes during the 5th week of gestation. Expression of the earliest testis (Sertoli cell)-specific genetic markers, SRY (sex-determining region Y) and SOX9 (SRY-box 9), begins at between 41 and 44 days (Hanley et al, 2000) followed by the histologic appearance of Sertoli cells and testicular cords in male fetuses by 9 weeks of age (Ostrer et al, 2007). Migrating mesonephric cells contribute to testis cord formation as well as testicular endothelial cells (Cool and Capel, 2009) The germ cell marker, c-KIT, first identified at 7 weeks of age, is present in an increasing number of cells until 12 weeks, with subsequent reduced expression as maturation to intermediate germ cells progresses (Ostrer et al, 2007). By the third trimester, a third stage of germ cells, prespermatogonia, predominates within the testis. Leydig cells can be identified by cell-specific

staining by 9 weeks and by peritubular myoid cells by 12 weeks of age.

Gonadal differentiation is more complicated than the original concept of ovarian development as the default pathway because emerging evidence suggests that activation of specific gene path-ways is required for both male and female sex determination in mice (Blecher and Erickson, 2007; Cool and Capel, 2009). Sry has been considered the master male gene, but other genes required for gonadal determination act upstream of Sry and its downstream effects on Sox9 expression are indirect via derepression of an inter-mediate gene, likely Rspo1 (R-spondin homolog). Testicular deter-mination is directly dependent on activation of Sox9 and Fgf9 (fibroblast growth factor-9), whereas ovarian determination is dependent on activation of Rspo1 and Wnt4 (wingless-related MMTV integration site-4) and the appropriate dosage of the X-linked Nr0b1 (nuclear receptor subfamily 0, group B, member 1, also known as Dax1) gene.

Hormonal function of the human fetal testis is critical for mas-culinization of the reproductive tract and testicular descent. Fetal Leydig cell development is divided into three phases: a prolifera-tion and differentiation phase between 7 and 14 weeks’ gestation, a maturation phase until 18 weeks, and an involution phase that continues until term (Svechnikov and Soder, 2008). Synthesis of testosterone by fetal Leydig cells starts as early as 6 to 7 weeks’ gestation and appears to be initially independent of gonadotropin stimulation. However, placental human chorionic gonadotropin (hCG) stimulates a peak in androgen production at 14 to 16 weeks’ gestation and the testis then becomes responsive to fetal lutein-izing hormone (LH). Insulin-like 3 (INSL3) of Leydig cell origin is measurable in human amniotic fluid as early as 13 weeks’ gesta-tion (the earliest time point studied) and peaks at 15 to 17 weeks (Anand-Ivell et al, 2008; Bay et al, 2008). Fetal Sertoli cells produce antimüllerian hormone (AMH; also called müllerian-inhibiting substance [MIS]) soon after they differentiate; the human fetal müllerian duct is responsive to AMH before week 8 of gestation, and the process of regression occurs between 9 and 10 weeks ( Josso et al, 2006). Evidence from animal models and indirect clinical evidence suggests that INSL3 and testosterone are the key hormones required for testicular descent.

3558 SECTION XVII ● Pediatric Urology

the morphologic events have been well studied in mammals. Knowledge of the regulation of testicular descent is inferred from studies of human diseases that include cryptorchidism and/or from animal models.

The human indifferent gonad develops adjacent to and becomes suspended from the mesonephros, which has replaced the pro-nephros by 5 weeks’ gestational age (Lemeh, 1960). A rudimentary cranial mesonephric ligament connects to the diaphragm, disap-pearing by 13 weeks as the mesonephros regresses (Barteczko and Jacob, 2000) (Fig. 132–1). There is no direct connection between the gonad and this ligament; therefore no “cranial gonadal liga-ment” exists in humans as noted in other species. Using fixed sections, Barteczko and Jacob observed an “inner” or transabdomi-nal descent of the human testis from a position at vertebral levels C7-T8 to T9-L3 between 5 and 7 weeks’ gestation and to the sacral level by 10 weeks; using dissections, others described the testis at the level of L4 by the 7th week (Lemeh, 1960) or always “close to the groin” (Wyndham, 1943). Caudal movement of the ovary is prevented by the ovarian ligament and development of the mül-lerian ducts.

Barteczko and Jacob (2000) described five major phases of tes-ticular descent in the human fetus (Fig. 132–2):

Phase 1: The caudal mesonephros contacts the future gubernaculum at the internal inguinal ring (5 weeks’ gestation).

Phase 2: The genitofemoral nerve accompanies the newly formed gubernaculum (abdominal, interstitial, and subcuta-neous portions) and processus vaginalis (7 weeks).

Phase 2a: Growth of the gubernaculum, deepening of the pro-cessus vaginalis, and extension of cremaster muscle fibers into the interstitial gubernaculum occurs (8 to 10 weeks).

Phase 3: Growth of the testis and regression of the müllerian ducts and mesonephros occurs; the gubernaculum remains a thin cord in both sexes (10 to 12 weeks).

Phase 3a: The testis overrides the genital ducts and contacts the gubernaculum, which begins its swelling phase in males (12 to 14 weeks).

Phase 4: Swelling of the gubernaculum, development of the cremaster muscle, and migration of the processus vagi-nalis produce widening of the inguinal canal (14 to 20 weeks).

Steroid hormones exert their effects via sex steroid receptors in the reproductive tract and testis. Recent studies show that andro-gen receptor (AR) and estrogen receptor-β (ERβ) are expressed in the undifferentiated gonad at 7 weeks of age, although their role in testicular development is unclear (Shapiro et al, 2005; Boukari et al, 2007). AR is present primarily in peritubular myoid cells and in some Leydig and interstitial cells but absent in Sertoli cells during the fetal period. Because androgens inhibit AMH production by Sertoli cells, the absence of an AR in these cells during fetal life allows unfettered expression of AMH during this period (Boukari et al, 2009). ERβ localization is most extensive, being observed in germ, peritubular myoid, Sertoli, and some Leydig cells by 13 weeks and decreasing by 22 to 24 weeks, whereas expression of estrogen receptor-α (ERα) is limited (Shapiro et al, 2005) or absent (Boukari et al, 2007) in the human fetal testis. Concomitant expres-sion of aromatase during the same time frame suggests that locally produced estrogen may play a role in testicular development.

Significant changes in reproductive hormone secretion and tes-ticular development occur in the neonatal period (Grumbach, 2005). Fetal Leydig cells regress after birth, followed by emergence of a neonatal Leydig cell population at 2 to 3 months of age (Prince, 2001) and a peak in testosterone and INSL3 levels (Bay et al, 2007) that follows a surge in serum gonadotropin levels. As postnatal hormonal levels wane, the fetal Leydig cells either degenerate or regress to immature Leydig/interstitial cells that are partially differentiated and less responsive to LH. In the first months of life, intratubular gonocytes migrate to the basement membrane and differentiate into type A spermatogonia, which comprise a subset of spermatogonial stem cells (Culty, 2009). Sertoli cell proliferation occurs in the first year of life and is a major determinant of ultimate testicular size (Sharpe et al, 2003). The characteristics of testicular growth during childhood vary depending on the method of analysis. Main and colleagues reported significant growth of normal testes between birth and 3 months of age based on ultrasound measurements and on signifi-cantly larger testicular size in Finnish as compared with Danish boys at birth and 3 and 18 months, a difference attributable to genetic and/or environmental effects (Main et al, 2006b). Kuijper and coworkers observed a peak in testicular ultrasound volume at 6 months of age followed by a decline to baseline (Kuijper et al, 2008). In contrast, in an autopsy series, Berensztein and associates noted doubling of testicular weight during the first 3 weeks of life with slowed growth thereafter, suggesting that major growth occurs prior to the postnatal hormone surge and a gonadotropin-independent mechanism (Berensztein et al, 2002). This growth was associated with a rate of proliferation exceeding the rate of apoptosis in Leydig, germ, and Sertoli cells before the second month of age with increased apoptosis thereafter and little subse-quent growth of the testes before age 6. In their autopsy series of older children, Müller and Skakkebaek (1983) reported a 2.6-fold increase in testicular size between the first year of life and age 10, with a significant increment between all age groups (birth to 1, 1 to 5, and 5 to 10 years) in both size and tubular length. Overall, the data suggest a major increment in testicular growth during the neonatal period, but the factors responsible for age-specific cellular proliferation, gonocyte differentiation, and testicular growth are not clearly defined.

Gubernacular Development and Testicular DescentThe physiology of normal testicular descent and the etiology of abnormal descent in humans remain poorly understood, whereas

Figure 132–1. Development of the cranial mesonephric ligament (CML) and gonad (G) during embryonic regression of the mesonephros (M). Asterisks denote the anlage of the diaphragm; long arrows show the cranial mesonephric ligament. (From Barteczko KJ, Jacob MI. The testicular descent in human: origin, development and fate of the gubernaculum Hunteri, processus vaginalis peritonei, and gonadal ligaments. Adv Anat Embryol Cell Biol 2000;156:III-X, 1–98.)

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CHAPTER 132 ● Abnormalities of the Testis and Scrotum and Their Surgical Management 3559

gubernaculum is unattached distally during and after transingui-nal passage (Fig. 132–3). Settling of the gubernaculum and testis into the preformed scrotum is gradual. The scrotum itself develops from genital swellings that are first visible at 7 weeks and fuse by 10 to 12 weeks in response to circulating dihydrotestosterone. Passage of the testis into the inguinal canal rarely occurs prior to week 22 in the human fetus, and the majority of testes are scrotal

Phase 5: Release of the distal subcutaneous attachment of the gubernaculum and transinguinal passage of the testis occur (20 to 28 weeks).

Phase 5a: Further caudal movement of the testis into the scrotum is accompanied by regression of the gubernaculum (7th month and beyond).

The careful in-situ anatomic observations by Barteczko and Jacob (2000) throughout gestation help clarify some aspects of human testicular descent. For example, transabdominal move-ment of the testis occurs before sexually dimorphic changes in the gubernaculum and is presumably not a male hormone–specific event. The subsequent male-specific swelling of the gubernaculum parallels the peak in Leydig cell secretion of testosterone (14 to 16 weeks) and INSL3 (15 to 17 weeks). The genitofemoral nerve accompanies and precedes the gubernaculum and developing pro-cessus vaginalis in both sexes beginning at an early stage (7 weeks), and both smooth (abdominal) and skeletal (interstitial and subcu-taneous) muscle fibers occur within the three segments of the gubernaculum. Both muscle types were also observed by some (Wyndham, 1943; Lemeh, 1960) but not others (Heyns, 1987; Costa et al, 2002; Niikura et al, 2008) observers. However, studies of the in-situ gubernaculum beginning at 20 weeks clearly show the presence of peripherally and centrally located striated muscle bundles (Barteczko and Jacob, 2000; Niikura et al, 2008) and infil-tration of the gubernaculum by the genital branch of the genito-femoral nerve (Tayakkanonta, 1963). Controversy exists as to whether these skeletal cremaster muscle fibers are of similar origin and/or originate from abdominal wall musculature or from within the gubernaculum itself (van der Schoot, 1996; Barteczko and Jacob, 2000; Niikura et al, 2008). The processus vaginalis and cremaster muscle may facilitate transit of the testis and gubernacu-lum, but their exact role remains unknown.

Swelling of the gubernaculum is critically important to allow enlargement of the inguinal canal and testicular passage and is the result of both cellular pro-liferation and production of extracellular matrix (Heyns, 1987). Once the canal is created, unknown mechanical factors trigger a typically rapid transinguinal passage of the testis. The

Figure 132–2. Overview of human testicular descent. Sagittal view (top) and transverse sections (bottom) of 1, gonad; 2, mesonephros; 3, wolffian and müllerian duct; 4, vas deferens/epididymis; 5, gubernaculum—a, abdominal; i, interstitial; s, subcutaneous part; 6, processus vaginalis; 7, internal inguinal ring; 8, external inguinal ring. Straight arrows (phase I) show ventral side; asterisks (phases I to IIIa) show the link between the caudal pole of the testis and dorsal mesenchyme of genital ducts; curved arrow (phase III) shows direction of testicular migration; short arrows (phases IIIa to IV) indicate attachment between the testis or epididymis and gubernaculum; oval arrowline (phase V) indicates no connection between the boltlike gubernaculum and neighboring structures. (From Barteczko KJ, Jacob MI. The testicular descent in human: origin, development and fate of the gubernaculum Hunteri, processus vaginalis peritonei, and gonadal ligaments. Adv Anat Embryol Cell Biol 2000;156:III-X, 1–98.)

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Figure 132–3. The distally unattached human gubernaculum at 25 weeks of gestation (215 mm CRL) just before transinguinal testicular descent. T, testis; G, gubernaculum; P, penis; S, scrotum. (From Heyns CF. The gubernaculum during testicular descent in the human fetus. J Anat 1987;153:93–112.)


innervated by the nerve beginning as early as at 7 weeks’ gestation (Lemeh, 1960; Tayakkanonta, 1963; Barteczko and Jacob, 2000; Niikura et al, 2008).

In summary, the gubernaculum develops in both sexes beginning early in the second month of gestation and testicular hormones stimulate development of the guber-naculum and testicular descent in the second and third trimesters. Enlargement, distal detachment and migration of the gubernaculum are key events that facilitate and direct caudal movement of the testis. In humans, the factors required for these events are incompletely known but likely include secretion of INSL3 and androgen and presumably intact innervation by the genitofemoral nerve.

after week 27; time spent in the inguinal canal seems to be limited for the majority of human fetal testes (Heyns, 1987; Sampaio and Favorito, 1998). Early innervation of the gubernaculum and the importance of the genitofemoral nerve in testicular descent in rodents, as well as the rapidity of transinguinal passage, suggest a neuromuscular mechanism.

Regulation of Testicular DescentDirect evidence for hormonal control of testicular descent is based entirely on studies in animal models, primarily rodents. The rel-evance of rodent data to humans is controversial because of ana-tomic differences, which in mice and rats include a less prominent interstitial gubernaculum, a cranial gonadal ligament, an elon-gated cord connecting the gubernaculum to the epididymis, a well-developed intrinsic cremaster muscle located in the outer layer of the gubernaculum, an absent inguinal canal, and failure of closure of the processus vaginalis (Wensing, 1988). However, some observers argue that the similarities between species are suf-ficiently strong to warrant translational studies of these models (van der Schoot, 1996; Harnaen et al, 2007).

Rodent studies provide strong evidence that testicular INSL3 and androgen signaling pathways are the primary contributors to gubernacular development and testicular descent (Zimmermann et al, 1999; Adham et al, 2000; Overbeek et al, 2001). According to a paradigm developed by Hutson, testicular descent occurs in two phases—transabdominal and transinguinal—regulated by INSL3 and by androgens via the genitofemoral nerve, respectively (Hutson and Hasthorpe, 2005). However, animal models show that INSL3 and androgen synergistically stimulate cellular prolif-eration and growth of the gubernaculum (Adham et al, 2000; Emmen et al, 2000; Kubota et al, 2002) and that both INSL3 binding and androgen receptor expression are present before and during the swelling phase of the fetal rat gubernaculum (Koskim-ies et al, 2003; McKinnell et al, 2005; Staub et al, 2005). Moreover, INSL3 and testosterone levels peak after week 12 in the human fetus, concomitant with gubernacular swelling, although transab-dominal testicular descent occurs earlier, prior to 10 weeks’ gesta-tion. In mice, INSL3 signaling promotes development of the processus vaginalis, and androgen signaling causes regression of the cranial gonadal ligament (Adham et al, 2002; Koskimies et al, 2003; Adham and Agoulnik, 2004), a structure that does not exist in the human fetus. Clues about other gene pathways that partici-pate in the process of testicular descent are provided by known transgenic mouse models and human syndromes with phenotypes that include cryptorchidism (Barthold, 2008; Foresta et al, 2008). Transgenic deletion of either of two homeobox genes, Hoxa10 and Hoxa11, is associated with isolated cryptorchidism in mice. Hoxa10 appears to function independently of gonadotropin or INSL3 sig-naling (Feng et al, 2006). At present, little is known of the role of these and other gene candidates in the process of testicular descent.

A role for the genitofemoral nerve in guiding and/or promoting passage of the gubernaculum is supported by rodent studies of Hutson and colleagues, who propose that release of calcitonin gene-related peptide (CGRP) from the nerve stimulates develop-ment and function of the gubernaculum (Yamanaka et al, 1993; Chan et al, 2009). Studies of rats with inherited cryptorchidism suggest that innervation and/or muscle development within the gubernaculum is disrupted (Hrabovszky et al, 2001; Barthold et al, 2008). While a role for CGRP release from the genitofemoral nerve in human fetuses remains undefined, it is clear that the human gubernaculum contains and is surrounded by muscle and is

Key Points: Embryology of Testicular Development and Descent

● Gonadal determination involves separate genetic pathways for development of testis and ovary.

● Sry is a master switch that derepresses the critical testis determining genes Sox9 and Fgf 9.

● Differentiation of gonocytes and Sertoli and Leydig cells occurs between 5 and 9 weeks’ gestation.

● Levels of the Leydig cell hormones testosterone and INSL3 peak between 14 and 17 weeks’ gestation and are critical for testicular descent.

● The gubernaculum, the guide for testicular descent, appears at 7 weeks’ gestation and begins male-specific proliferation and swelling between 12 and 14 weeks.

● Dramatic swelling of the gubernaculum sets the stage for testicular descent, and innervation via the genitofemoral nerve may trigger transinguinal passage of the testis.

● The testis finishes transabdominal descent by 10 weeks, rapidly passes through the inguinal canal between 20 and 28 weeks, and is dependent in the scrotum in most boys by birth.

CRYPTORCHIDISM (UNDESCENDED TESTIS)Cryptorchidism is one of the most common disorders encountered in pediatric urology and has been studied extensively. Despite this, knowledge of the causes and prediction of the consequences of the disease remains limited. Moreover, the quality of evidence that is used to support clinical guidelines for diagnosis and treatment is surprisingly low (Gapany et al, 2008; Turner, 2009).

DefinitionsDiffering terminology has been used to describe patients with nonscrotal testes; use of the following definitions is recommended. Normal scrotal position has been defined as positioning of the midpoint of the testis at or below the midscrotum (Wohlfahrt-Veje et al, 2009). Although “high scrotal testes” are not routinely con-sidered undescended by most clinicians, they have been included in the definition of undescended testis in some epidemiologic studies (Sijstermans et al, 2008). This is likely a heterogeneous group that includes stable descended testes that reside above the scrotal midpoint and undescended “gliding” testes (Hack et al, 2007), which are not stable. Undescended testis is the absence of one or both testes in normal scrotal position and during initial


cryptorchidism referred to a urology practice when younger than 6 months of age, 16% had spontaneous testicular descent versus 0% of those presenting after 6 months; in contrast, previous studies reported a 50% to 75% rate of spontaneous postnatal tes-ticular descent (Wenzler et al, 2004). Suomi and associates (2006) noted spontaneous descent in significantly more Danish (68%) than Finnish (45%) boys at 3 months of age, likely owing to increased severity of the disease in the latter group. Similarly, in a recent longitudinal study, extrascrotal testes were much less likely to descend by 1 year of age (50%) than high scrotal testes defined as cryptorchid at birth (87.5%) (Acerini et al, 2009). The long-term risk of recurrent cryptorchidism was not determined in these studies and is difficult to ascertain because of short follow-up. Spontaneous descent is more likely and may occur later in prema-ture infants.

Retractile and Acquired Undescended TestesIn the past, cryptorchidism was considered a congenital anomaly identifiable at birth, with spontaneous descent possible during the postnatal period. However, since first reported more than 30 years ago (Myers and Officer, 1975), substantial evidence indicates that the diagnosis of cryptorchidism may be “acquired,” that is, made in cases of apparent full descent at birth or after spontaneous descent of a cryptorchid testis (Barthold and Gonzalez, 2003; Taghizadeh and Thomas, 2008). Except for diagnosis at an average age of 8 to 9 years and lower testicular position, other characteristics of testicular “ascent” or “acquired” cryptorchidism are similar to those observed in cases of congenital cryptorchidism. The reason for a later diagnosis remains unknown; theories include presence of a fibrous remnant of the processus vaginalis that tethers or foreshortens the cord over time or mobility of the testis within an open sac. However, it is most likely that the testis is incompletely descended from birth, because many are localized within the superficial inguinal pouch (Barthold and Gonzalez, 2003). These testes may be highly mobile and initially appear descended until somatic growth results in relative widening of the distance between testis and scrotum (Redman, 2005; Agarwal et al, 2006).

A diagnosis of cryptorchidism beyond the neonatal period may be more likely in boys with retractile testes. In an unselected population, the testis was reported to be suprascrotal on initial examination in up to 30% of boys at 4 years of age but intrascrotal in 100% by age 12 (Farrington, 1968). Both prospective and retrospective studies of the natural history of retractile testes support the concept that a subset of these becomes undescended over time. However, a selection bias exists in studies of the risk of cryptorchidism in boys with retractile testes, because those referred for follow-up by specialists are those with the most severe retractil-ity. For example, Wyllie (1984) prospectively studied a cohort of 100 boys with unilateral retractile testis and identified 64 cases in which testicular position, as documented by the distance between the pubic tubercle and midtestis, and/or testicular size, as esti-mated by orchidometer, was reduced after 5 years of follow-up. Orchidopexy was performed in 45 of these cases, although specific documentation of testicular position and size as indications for surgery were not reported. Findings of retrospective case series also suggest that cryptorchidism is ultimately diagnosed in about 33% of boys with significantly retractile testes followed longitudinally by the same observer(s) (La Scala and Ein, 2004; Agarwal et al, 2006). In contrast, only 7% of 172 boys followed a mean of 26 months required orchidopexy in a more recent study (Stec et al, 2007). These data suggest that a significant minority of retractile testes become suprascrotal over time. Careful, often

clinical evaluation may refer to palpable cryptorchid testes or to nonpalpable testes, which are either cryptorchid or absent. Most absent testes are vanishing, present initially in develop-ment but are lost owing to vascular accident or torsion unilaterally (monorchia) or, very rarely, bilaterally (anorchia) (Abeyaratne et al, 1969). Agenesis refers to a testis that was never present and therefore associated with ipsilateral müllerian duct persistence. Congenital cryptorchidism refers to testes that are extrascrotal at birth, and recurrent cryptorchidism is when testes descend spontaneously postnatally but subsequently return to a nonscrotal position. The terms testicular ascent or acquired cryptorchi-dism are used in situations when cryptorchid testes are docu-mented as scrotal at a previous examination without intervening inguinal surgery. Secondary cryptorchidism and testicular retraction apply to testes that are suprascrotal after inguinal hernia repair and as a complication of orchidopexy, respectively. Testicular malposition after hernia repair is due to either postop-erative scarring or primary maldescent. Retractile testes are scrotal testes that retract easily out of the scrotum but can be manually replaced in a stable scrotal position and remain there at least temporarily. Testes that are significantly retractile, that is, those that rarely remain in a stable scrotal position (spontaneously or with manipulation) and/or are located at rest in the high scrotum, may or may not be truly undescended.

Epidemiology and PathogenesisCryptorchidism is one of the most common congenital anomalies, occurring in 1% to 4% of full-term and 1% to 45% of preterm male neonates (Sijstermans et al, 2008). It is a component of over 390 syndromes (Winter-Baraitser Dys-morphology Database, http://www.lmdatabases.com); the most common are listed in recent reviews (Foresta et al, 2008; Virtanen and Toppari, 2008). The majority of cases are isolated, with the ratio of nonsyndromic to syndromic cryptorchidism reported as greater than 6 : 1 in a large cohort (Boyd et al, 2006). In a small percentage of syndromic cases associated with deficiency or insen-sitivity of hypothalamic-pituitary-gonadal (HPG) axis hormones, the etiology of testicular maldescent is known. The pathogen-esis of isolated cryptorchidism remains largely unknown but is most likely multifactorial, involving both genetic and environmental risk factors.

Nonsyndromic Congenital CryptorchidismStudies of the prevalence of isolated cryptorchidism at birth are complicated by confounding factors that include subjectivity of the examination and differences in the definition of undescended testis (inclusion/exclusion of high scrotal testes) and in study populations and study design (Sijstermans et al, 2008). Although most studies support a prevalence at birth of 2% to 4% and at 3 months of age of 1% to 2%, this varies geographically, with fre-quency as high as 8% in some studies (Virtanen and Toppari, 2008), supporting the possibility of an increase over time. However, other data suggest that country-specific trends are not increasing (Abdullah et al, 2007; Cortes et al, 2008; Bonney et al, 2009) and overall there do not appear to be reproducible trends in prevalence (Sijstermans et al, 2008). Perinatal risk factors associated with cryptorchidism include prematurity, low birth weight/small for gestational age, breech presentation, and maternal diabetes (Damgaard et al, 2008; Virtanen and Toppari, 2008).

The reported frequency of spontaneous testicular descent after birth also appears to vary substantially between studies, likely owing to similar confounding factors. Of 95 patients with

http://www.lmdatabases.com


presentations and apparently deleterious mutations may exist in normal family members, as recently noted for an INSL3 mutation showing reduced receptor activation (El Houate et al, 2007). A nonsynonymous polymorphism of the RXFP2 gene, T222P, was considered a strong etiologic candidate for cryptorchidism based on absence in normal controls and in-vitro studies showing cur-tailed cell membrane localization and activation of the abnormal receptor (Bogatcheva et al, 2007). However, cases and controls in a different European population subset were found to have a similar frequency of the T222P allele (Nuti et al, 2008). Although these data suggest that mutations of INSL3 and RXFP2 are infre-quent in cases of cryptorchidism, it is possible that noncoding variants that alter expression levels of the protein have yet to be identified.

Analysis of other potential candidate genes for human cryptor-chidism has failed to yield reproducible results. HOXA10 muta-tions reported by Kolon and colleagues (1999) were not confirmed in additional series, nor were mutations identified in HOXA11 (Bertini et al, 2004; Wang et al, 2007). A specific haplotype of the gene encoding ERα (ESR1) has not shown consistent association with cryptorchidism in three case-control series (Yoshida et al, 2005; Galan et al, 2007; Wang et al, 2008). Similar varying results have been reported in studies of trinucleotide repeat number in exon 1 of the androgen receptor, although more recent work sug-gests a possible association with cryptorchidism (Ferlin et al, 2007). Microdeletions of the Y chromosome have also been studied in infertile men with and without a history of cryptorchidism, and no consistent association was observed (reviewed in Gurbuz et al, 2008). A specific polymorphism of the steroidogenic factor 1 (SF1) gene that encodes a transcription factor that regulates expression of INSL3, RXFP2, and steroidogenesis genes was recently reported to exist more commonly in cryptorchid Japanese males (Wada et al, 2006). Failure to identify consistent differences in genomic variants for many of these candidates may be influenced by con-founding factors such as race and by insufficient sample size. Although multiple genetic variants likely contribute to the risk of nonsyndromic cryptorchidism, most remain unknown at this time.

Environmental Risk FactorsSharpe and Skakkebaek (2008) proposed that nonsyndromic crypt-orchidism is one component of the “testicular dysgenesis syn-drome,” a constellation of reproductive abnormalities including testicular cancer, hypospadias, and reduced sperm counts associ-ated with exposure to antiandrogenic and/or estrogenic environ-mental endocrine-disrupting chemicals (EDCs). However, some question both the existence of testicular dysgenesis syndrome in humans, because of lack of epidemiologic association between these abnormalities, and the evidence for environmental etiology (Akre and Richiardi, 2009). The concern for a link between EDCs and cryptorchidism arose because of a reported increased risk of cryptorchidism after maternal exposure to diethylstilbestrol (DES) (Gill et al, 1979). This association was observed in rodents but was not confirmed in other clinical case-control studies (Leary et al, 1984); however, in a recent large cohort study of 1197 men previ-ously exposed to DES and 1038 unexposed men, the relative risk (RR) of cryptorchidism was 1.9 overall (confidence interval [CI] 1.1 to 3.4). When data were subdivided based on gestational age of less than 11 weeks and exposure greater than or equal to 5 g, the relative risks were 2.9 (CI 1.6 to 5.2) and 3.2 (CI 1.7 to 6.0), showing that early and significant exposure presents the clearest risks (Palmer et al, 2009). Data supporting a link between other EDCs and cryptorchidism are less clear. Animal models suggest a

serial, physical examination may be necessary to accu-rately determine testicular position and need for intervention.

Two recent longitudinal population-based cohort studies have provided some preliminary information regarding the risk of acquired cryptorchidism in the general population during child-hood (Acerini et al, 2009; Wohlfahrt-Veje et al, 2009). In a study from the United Kingdom, 742 infants were followed with serial examinations for 2 years after birth with complete follow-up in 326. The prevalence of extrascrotal testes was 2.7% at birth (27% nonpalpable, surgical findings not reported); and 0.2%, 1.8%, 0.3%, and 0% of testes in the studied population became extrascro-tal at 3, 12, 18, and 24 months, respectively. Including high scrotal testes, a total of 5.7% were identified as cryptorchid at birth and 1% to 4% rose to a high scrotal position with each follow-up visit. As expected, suprascrotal testes in neonates were much less likely to descend spontaneously (41%) than high scrotal testes (84%). In a series from Finland, cryptorchidism was present at birth in 94 of 1072 boys (0.9%) and 509 of the noncryptorchid boys were followed at 6- to 18-month intervals until 4.5 to 10 years of age. Of those observed, seven testes became suprascrotal and five became high scrotal, with the change in position occurring during the first 36 months of life. These studies suggest regional differ-ences in both congenital and acquired cryptorchidism, but both suggest a low risk that scrotal testes will become suprascrotal in the first few years of life. However, cases diagnosed during childhood comprise a significant number of those requir-ing orchidopexy and yearly well-child screening is indicated.

Genetic SusceptibilityGenetic studies of cryptorchidism suggest that the disease is heri-table but that susceptibility is likely polygenic and multifactorial. Clustering of cryptorchidism has been reported in a number of families affecting multiple individuals in the same generation and variable phenotype (Minehan and Touloukian, 1974; Pardo-Mindan et al, 1975; Czeizel et al, 1981; Savion et al, 1984). Extended pedigrees were not usually examined, but autosomal dominance with reduced penetrance was most often cited as the probable mode of inheritance. Population case-control studies also support genetic contribution to the disease. Familial aggregation suggesting moderate genetic risk was reported in a recent large cohort study of more than 1 million male births in the Nether-lands based on extensive hospital registry data (Schnack et al, 2008). Recurrence risk ratio (RR) was 10.1 in twins, 3.5 in brothers, and 2.3 in offspring and were significantly higher in maternal than in paternal half-brothers. Previous smaller studies reported a 5- and 7- to 10-fold increased risk of cryptorchidism in fathers and brothers, respectively, of affected as compared with unaffected subjects (Czeizel et al, 1981; Jones and Young, 1982; Elert et al, 2003). These and another recent study (Jensen et al, 2010) support the possibility that maternal factor(s), or X-linked risk alleles, influence expression of the disease.

Based on mouse models, INSL3, its receptor, relaxin/insulin-like family peptide receptor 2 (RXFP2), HOXA10, and HOXA11 were considered the most likely candidate genes for human nonsyn-dromic cryptorchidism. However, case-specific DNA coding vari-ants of INSL3 and RXFP2 are reported in only 0.6% to 1.8% and 1.6% to 2.9% of persistently cryptorchid males, respectively, and in-vitro assays suggest that few of these appear to be functionally significant (Foresta et al, 2008). Notably, apparent mutations in these genes are associated with a range of phenotypes encompass-ing unilateral/bilateral and persistent/spontaneously resolving


age 4 to 5 years) (Yamanaka et al, 1991) and also in a case-control study of 12-month-old boys (n = 20 per group) in whom levels did not change after orchidopexy (Demircan et al, 2006). However, in another study no differences in AMH levels were seen in 1- to 6-month-old cryptorchid (n = 43) versus control (n = 113) boys (Pierik et al, 2009).

These studies suggest that at least a subset of boys with cryptorchidism have measurable abnormalities in pitu-itary and/or gonadal hormone secretion during infancy without syndromic endocrine dysfunction. Inconsistent findings between studies are likely based on timing and type of assays, sample size, and heterogeneity based on age, severity, genetic background, and/or other interindividual differences. Life-style factors may also interfere with testicular descent and func-tion via hormonal or nonhormonal effects; examples are the recent observation that smoking is associated with cryptorchidism in some case-control series (Thorup et al, 2006; Jensen et al, 2007) and the reduced expression of the Desert hedgehog (DHH) gene that is involved in Leydig cell differentiation in human fetuses (Fowler et al, 2008). Multiple genetic and environmental factors likely contribute to cryptorchidism, complicating identification of risk factors in case-control studies.

Syndromic CryptorchidismUndescended testes are frequently present in diseases associated with reduced androgen production and/or action, such as andro-gen biosynthetic defects, androgen insensitivity, Leydig cell agen-esis, and gonadotropin deficiency disorders (Barthold et al, 2000; Foresta et al, 2008) that are typically associated with generalized failure of masculinization and are not reviewed here. AMH biosynthesis or receptor defects are also associated with cryp-torchidism or transverse testicular ectopia (Josso et al, 2006). Gubernacular defects that are observed in these patients may be due to hindrance of descent by retained müllerian ducts (Barteczko and Jacob, 2000) and/or through loss of direct prolifera-tive effects of AMH on the gubernaculum (Kubota et al, 2002). The frequency of Klinefelter syndrome (47,XXY) is 1.8% in large series of primarily nonsyndromic cryptorchidism but is more frequent when other anomalies, particularly hypospadias, are present (Sasagawa et al, 1996; Moreno-Garcia and Miranda, 2002). Other genomic rearrangements and trisomies, including Down syn-drome (trisomy 21), are associated with cryptorchidism (Hadzise-limovic, 1983).

Certain anomalies are associated with increased risk of cryptor-chidism, many related to musculoskeletal, central nervous system (CNS), or abdominal wall/gastrointestinal defects. These include all cases of classic prune-belly (triad or Eagle-Barrett) syndrome; 80% of those of spigelian hernia (Durham and Ricketts, 2006); and 41% to 54% of cerebral palsy (Rundle et al, 1982; Cortada and Kousseff, 1984), 38% of arthrogryposis (Fallat et al, 1991), 15% of myelomeningocele (Ferrara et al, 1998), 16% to 33% of omphalo-cele, 5% to 15% of gastroschisis (Kaplan et al, 1986; Koivusalo et al, 1998), 19% of imperforate anus (Cortes et al, 1995b), 12% to 16% of posterior urethral valve (Krueger et al, 1980; Heikkila et al, 2008), and 6% of umbilical hernia (Kaplan et al, 1986) patients. Multisystem anomalies are often associated with ompha-locele (80%) and prune-belly syndrome (45%), suggesting a syn-dromic etiology (Loder et al, 1992; Koivusalo et al, 1998). Depue (1988) also reported a significant association of cryptorchidism with CNS dysfunction, particularly cerebral palsy (RR = 34), low intelligence quotient (RR = 2.7), and hypotonia (RR = 3.6). Cortes and associates (1998) identified an association between renal and T10 to S5 spinal anomalies and cryptorchidism, with the affected

relationship between prenatal exposure to antiandrogenic EDCs and risk of cryptorchidism and other reproductive endpoints and suggest additive effects of chemical mixtures, although levels of exposure are much higher than applicable clinically (Rider et al, 2009). In humans, data supporting a correlation between exposure to antiandrogenic and/or estrogenic EDCs such as pesticides, flame retardants, and phthalates and occurrence of cryptorchidism are mostly indirect or suggestive (Weidner et al, 1998; Pierik et al, 2004; Damgaard et al, 2006; Main et al, 2006a, 2007; Fernandez et al, 2007; Krysiak-Baltyn et al, 2010). Strong correlations between single chemicals or classes of EDCs and risk of cryptorchidism may be difficult to demonstrate in view of the presumed heterogeneity of susceptibility to the disease, but the wide variety of EDCs to which humans are exposed may allow for synergistic effects that are difficult to measure. However, at present, epidemiologic data are suggestive but do not strongly support the theory that environmental chemicals increase suscepti-bility to cryptorchidism.

Testicular hormones are required for testicular descent; there-fore, if defective hormone production and/or action contribute to the pathogenesis of cryptorchidism, hormone deficiency may persist postnatally. A number of prospective studies of varying size and quality are available that report postnatal hormone levels in cryptorchidism; although some data suggest that the HPG axis is abnormal, the results are conflicting. In the first reported series of cryptorchid and control boys undergoing hormonal evaluation in the first few months of life, serum testosterone was lower in 7 of 17 (41%) persistently cryptorchid boys but comparable to control levels in 4 of 25 boys with spontaneous testicular descent (Gendrel et al, 1978). In a small series of 60-day-old bilaterally cryptorchid (9) and control (14) boys, Facchinetti and associates (1983) also observed reduced plasma testosterone levels but no difference in plasma LH between groups. Raivio and coworkers (2003) reported both significantly reduced plasma testosterone as well as nonmea-surable androgen bioactivity in 3-month-old cryptorchid boys (n = 45; 31% bilateral, 44% with spontaneous descent), but androgen bioactivity was measurable in only 21 of 55 controls.

Additional infant hormone studies did not show lower levels in cryptorchid infants (De Muinck Keizer-Schrama et al, 1988, Bar-thold et al, 2004), but more recent data from the Netherlands did show reduced testosterone levels in cryptorchid infants (Pierik et al, 2009). In the largest study to date, Suomi and colleagues (2006) showed geographic differences in serum inhibin-B and follicle-stimulating hormone (FSH) levels but no differences in testosterone levels in cryptorchid infants from Finland (n = 88, 36% spontaneous descent) and Denmark (n = 34, 68% spontane-ous descent) as compared with 300 and 399 control boys, respec-tively. In a related cohort, INSL3 levels were reduced in cord blood but not in serum obtained at 3 months of age in persistently cryptorchid males (Bay et al, 2007).

Other studies of Sertoli/germ cell function as determined by serum assays in boys with cryptorchidism suggest that abnormali-ties may exist but data are inconsistent between studies. In a longitudinal study of 27 boys (mean age 4.8 years) undergoing orchidopexy, an increase in serum inhibin B was identified in a majority of cases 6 months postoperatively (Irkilata et al, 2004), but in another series of 62 boys (mean age 7.7 years) no differences were identified in inhibin B (or in serum LH, FSH, or testosterone) levels before or after hCG stimulation (Christiansen et al, 2002). AMH levels were measured in three prospective studies of boys with cryptorchidism as compared with age-matched controls. Lower AMH levels were seen in a subset of patients younger than 8 years of age included in a study of 104 cryptorchid boys (mean


classify a testis as palpable or nonpalpable, a critical step that influences further diagnosis and treatment. Every effort should be made by the examiner to determine the lowest position attainable by a palpable undescended testis. Manual downward pressure with one hand along the ipsilateral inguinal canal from the anterior iliac spine to the scrotum and palpation with the opposite hand helps to identify the lowest position of a palpable testis.

Difficulty in the clinical classification of cryptorchidism when the testis is palpable is related to both documentation of testicular position and differentiation of truly undescended from retractile testes, complicated by the fact that these entities may coexist. The gold standard for diagnosis remains careful examination of a child in several positions and confirmation of incomplete descent of the testis to a dependent scrotal position after induction of anesthesia. Prospective studies of intraobserver and interobserver variation show major differences in documentation of testicular position between examiners (Wit et al, 1987; Olsen, 1989). Olsen (1989) noted complete agreement between two examiners on scaled mea-sures of testicular position and mobility in only 5 (13.5%, 95% CI 4.5% to 28.8%) of 37 boys. Cendron and coworkers (1993) reported that preoperative testicular position correlates poorly with intra-operative findings. Variation in observed testicular position pre-operatively and postoperatively may influence assessment of prognosis and outcome in boys with cryptorchidism.

Nonpalpable TestesWhen a testis is nonpalpable, possible clinical findings at surgery include (1) abdominal or transinguinal “peeping” location (25% to 50%), (2) complete atrophy (“vanishing” testis, 15% to 40%), and (3) extra-abdominal location but nonpalpable due to body habitus, testicular size, and/or limited cooperation of the patient (10% to 30%) (Cendron et al, 1993; Cisek et al, 1998; Kirsch et al, 1998; Radmayr et al, 2003; Patil et al, 2005). If both testes are nonpalpable and not distal to the internal inguinal ring in a genetic male, at least 95% are abdominal with bilateral vanish-ing testis occurring rarely (Cendron et al, 1993; Moore et al, 1994). If neither vas nor spermatic artery is found at the time of laparoscopy, laparoscopic or surgical dissection of the paravesi-cal area and retroperitoneum up to the level of the kidney is required to exclude the presence of a testis. Pararenal or other abdominal testes may be associated with multicystic dysplastic or absent ipsilateral kidneys and/or nonunion of the testis and epididymis (Zaccara et al, 2004; Foley et al, 2005; Kim et al, 2005).

The etiology of vanishing testis is most likely torsion or vascular accident occurring after completion of genital masculinization but before fixation of the testis in the scrotum. Evidence supporting this etiology includes the presence of hemosiderin in remnant testicular “nubbins” excised at surgery (Turek et al, 1994) and reported cases of contralateral postnatal torsion (Gong et al, 1996). An enlarged contralateral testis (Huff et al, 1992) and absence of palpable intrascrotal “appendage” tissue (processus vaginalis, wolffian structures, or gubernaculum) are highly predic-tive of vanishing testis (Mesrobian et al, 2002). However, diag-nosis of a vanishing testis requires documentation of blind-ending spermatic vessels in the abdomen, inguinal canal, or scrotum. Endocrine evaluation in cases of suspected bilateral vanishing testis (anorchia) include elevated basal serum gonadotropin levels and no response to hCG stimulation; however, gonadotropins may be unexpectedly low in mid childhood in boys who are also unresponsive to hCG (Lustig et al, 1987; Lee, 2000). Therefore laparoscopic or surgical documentation of anor-chia is critical to avoid leaving small or dysgenetic abdominal

testis on the same side as the renal anomaly in 90% of cases. In addition, cryptorchidism associated with syndromes and CNS malformations is more commonly bilateral (Cendron et al, 1993; Cortes et al, 1995a). These data support common origins of crypt-orchidism and abnormalities of urogenital ridge, abdominal wall, lumbosacral spine, and CNS development.

Diagnosis and ClassificationTo best determine testicular position, boys should be examined in supine and, if possible, upright cross-legged and standing posi-tions. Abduction of the thighs contributes to inhibition of the cremaster reflex, or testicular elevation elicited by scratching the inner thigh. The examination should include documentation of testicular palpability, position, mobility, size, and possible associ-ated findings such as hernia, hydrocele, penile size, and urethral position. Patient distraction, a warm room and hands, use of liquid soap on the examiner’s hands, and repeated examinations also help to localize the testis and to limit cremaster muscle activ-ity and resultant difficulty in determining testicular position.

In large clinical series, the majority (75% to 80%) of unde-scended testes are palpable and 60% to 70% are unilateral; involve-ment of the right side is more common overall but less frequent in series of nonpalpable testes (Hadziselimovic, 1983; Cendron et al, 1993; Cortes et al, 2001; Giannopoulos et al, 2001). Position of undescended testes varies markedly with the population studied. In a comprehensive review of surgical patients, testes were abdom-inal in 34%, near the internal ring (“peeping”) in 12%, canalicular in 27%, and beyond the external ring in 27% (Docimo, 1995) whereas in a large single institutional series testes were abdominal in 3% to 10% of total cases, canalicular in 16% to 27%, with the majority distal to the external ring (Hadziselimovic, 1983; Moul and Belman, 1988; Cendron et al, 1993). In a large multi-institutional review of almost 40,000 European cryptorchid boys reported by Hadziselimovic (1983), 8% of testes were abdominal, 63% canalicular, 24% prescrotal, and 11% in the superficial ingui-nal pouch or ectopic. Moul and Belman classified all subinguinal testes with a lateral gubernacular attachment as ectopic (66% of their total cases).

Associated genital findings may warrant additional diagnostic studies that are best completed in the neonatal period. If both testes are nonpalpable, particularly if penile development is abnor-mal, karyotype and hormonal analyses are performed to rule out congenital adrenal hyperplasia and obviate the potential adverse effects of undiagnosed salt wasting. Hypospadias is associated with cryptorchidism in 12% to 24% of cases (Cendron et al, 1993; Moreno-Garcia and Miranda, 2002; Cox et al, 2008). If proximal hypospadias is present, chromosomal analysis is warranted because the frequency of abnormalities is high (32%) (Cox et al, 2008). Penile size may be small in boys with bilateral vanishing testes (also called testicular regression syndrome) or with hypogonado-tropic hypogonadism, in whom undescended testes are most com-monly inguinal. In these cases, measurement of testosterone, LH, and FSH levels in the first few months of life can facilitate identi-fication of hormone deficiency or anorchia.

Palpable TestesUndescended testes may be located along the line of normal descent between the abdomen and scrotum or in an ectopic posi-tion that is most commonly the superficial inguinal pouch (ante-rior to the rectus abdominis muscle) or, more rarely, in a perirenal, prepubic, femoral, peripenile, perineal, or contralateral scrotal position. Careful examination of these areas is needed to correctly


remnants that would otherwise be identified by laparoscopy (Wolffenbuttel et al, 2000; De Luna et al, 2003). Laparoscopy is the procedure of choice to confirm or exclude the pres-ence of a viable or remnant abdominal testis, unless a prominent scrotal nubbin is palpable with other clinical signs of monorchism.

The need for contralateral fixation of a solitary testis in cases of monorchism is not clear. The possibility that prenatal torsion is the etiology of vanishing testis (Gong et al, 1996) does not imply that the contralateral testis is likely to undergo a similar fate after the postnatal period. However, some surgeons recommend con-tralateral fixation to eliminate the risk of such a devastating com-plication (Rozanski et al, 1996) and/or because a contralateral bell-clapper deformity (incomplete testicular fixation to the tunica vaginalis) may be present (Bellinger, 1985; Al-Zahem and Shun, 2006).

Associated PathologyTesticular MaldevelopmentMany observational studies of the histologic development of prepubertal cryptorchid testes have been published. More than 40 years ago, Mancini and associates (1965) systematically reported germ cell counts and related arrested development of spermatogonia with progressive loss in cryptorchid testes. Sub-sequently, several large series, some with additional normal autopsy (Hedinger, 1982) or affected (hernia, hydrocele) (Hadzise-limovic et al, 1987a) control data and others that refer to these established age-dependent norms (Schindler et al, 1987; Huff et al, 1993; McAleer et al, 1995; Gracia et al, 2000; Cortes et al, 2001), have provided mainly consistent findings in cryptorchid boys. These data show that the number of spermatogonia per tubule (S/T) is reduced after infancy and fails to increase normally with age in cryptorchid and, to a lesser degree, in contralateral scrotal testes. The frequency of abnormal histology in the con-tralateral testis varies between studies, ranging from 22% to 95%, and is likely reflective of differences in patient populations, use of control data, and methodology. Moreover, variability within and between biopsy specimens from single testes is reported (Hedinger, 1982; Schindler et al, 1987). However, these data provide strong evidence that abnormal germ cell devel-opment is often present after early infancy in crypt-orchid testes. The degree of pathology was similar in true ectopic, superficial inguinal pouch, and ascending testes (Herzog et al, 1992; Hutcheson et al, 2000b; Rusnack et al, 2002) and was more severe in limited samples from patients with myelo-meningocele, posterior urethral valves, and prune-belly syndrome (Orvis et al, 1988; Patel et al, 2008). Findings are similar in retracted testes after hernia repair, suggesting primary instead of secondary cryptorchidism (Fenig et al, 2001). In other studies, higher S/T counts were correlated with reduced age-dependent interstitial fibrosis (Suskind et al, 2008), lower age at surgery, and increased likelihood of palpability (Tasian et al, 2009), but not volume (Noh et al, 2000), of cryptorchid testes. Regional differences in S/T counts were recently reported, potentially reflecting population differences in environmental exposures (Zivkovic et al, 2009).

Detailed studies of peritubular myoid and Sertoli cells in crypt-orchidism are lacking, but their abnormal development or func-tion may contribute to the observed germ cell abnormalities. The available data suggest disruption of prepubertal Sertoli cell mor-phology, failure of maturation at puberty, and evidence for reduced

testes in situ. AMH and inhibin-B levels may be useful in docu-menting the presence of functioning testicular tissue (Grumbach, 2005).

Inguinoscrotal ultrasonography and magnetic resonance imaging (MRI) are not usually helpful in the diagnosis and man-agement of nonpalpable testis (Elder, 2002). However, if a testis is nonpalpable when evaluated by an experienced examiner, the sensitivity of ultrasonography in identifying inguinal testes is reported to be as high as 95% to 97%, and abdominal testes are also seen in some cases (Cain et al, 1996; Nijs et al, 2007). Some of these testes are “peeping,” however, and best mobilized via a laparoscopic approach. Similarly, although MRI can be useful in some cases to identify nonpalpable abdominal testes, its accuracy is variable and the procedure requires sedation in younger chil-dren and often may not change the management approach (Yeung et al, 1999; Siemer et al, 2000). The superior accuracy of magnetic resonance angiography in localizing and differentiating viable from vanished testes (96% of 23 nonpalpable testes in 21 boys, mean age 2.5 years) has not been replicated in a recent study of younger boys (57% of 29 testes in 26 boys, mean age 13 months) (Yeung et al, 1999; Desireddi et al, 2008). One indication for MRI may be identification of an ectopic abdominal testis not localized by laparoscopy.

Diagnostic laparoscopy followed by laparoscopic orchidopexy if the testis is abdominal has become the preferred approach of many clinicians. Important observations include size and position of the spermatic vessels and vas; testicular size, quality, and posi-tion; and patency of the internal inguinal ring. The combination of a closed internal ring and a blind-ending spermatic artery and vas is most consistent with an abdominal vanishing testis, whereas a hernia is frequently but not always associated with a viable abdominal or distal testis (Elder, 1994; Moore et al, 1994). An atretic spermatic cord coursing through a closed inguinal ring is suggestive of a distal vanishing testis, but this finding may be subjective; and, conversely, normal-appearing vessels may be asso-ciated with both viable and vanishing testes (Zaccara et al, 2004). Moreover, the laparoscopic view may suggest abdominal blind-ending vessels despite a testis being present distally or in an ectopic abdominal position (Zaccara et al, 2004; Kim et al, 2005; Ellsworth and Cheuck, 2009).

The need for excision and contralateral scrotal orchidopexy in cases of vanishing testis remains controversial. Germ cells and/or tubules are consistently present in 5% to 15% of excised testicular remnants (Moore et al, 1994; Tennenbaum et al, 1994; Turek et al, 1994; Cortes et al, 1995a; De Luna et al, 2003; Renzulli et al, 2005), but the risk of malignancy is unknown. A single case of carcinoma in situ was reported by Rozanski and associates (1996) in a testicular remnant. Excision may be appropriate for remnants distal to an internal ring to allow confirmation that a viable testis is absent, because the laparoscopic appearance of the spermatic vessels and processus vaginalis may be deceiving and may not reliably exclude the presence of an inguinal testis (Ellsworth and Cheuck, 2009). Storm and colleagues (2007) performed laparo-scopic excision of vanishing testes in 56 patients without signifi-cant morbidity, although the position of the remnants in these patients was not clear. Because the testicular remnant is often in or near the scrotum, some advocate a primary scrotal approach when contralateral testicular hypertrophy (testicular length ≥ 1.8 cm) and a palpable scrotal “nubbin” are present (Belman and Rushton, 2003; Snodgrass et al, 2007). However, in cases of abdominal vanishing testes, a transscrotal search is time consum-ing and unproductive. Moreover, in cases of testicular-epididymal dissociation, scrotal nubbins may be mistaken for testicular


study indicates aberrant attachment lateral to the scrotum in 66% to 75% of cases (Moul and Belman, 1988). The processus is patent in approximately 50% of boys presenting with ascending testes, possibly related to older patient age and/or reduced severity of cryptorchidism in this group (Barthold and Gonzalez, 2003). Anomalies of the tunica and processus vaginalis in cryptorchidism predispose to development of testicular torsion or clinical hernia, respectively, in rare cases. Torsion of an undescended testis can occur at any age (reviewed by Zilberman et al, 2006) and may be confused with an incarcer-ated inguinal hernia. The risk of torsion is much higher in an undescended as compared with a descended testis and may be particularly high in children with neuromuscular disease such as cerebral palsy. Delay in diagnosis is common, and a high index of suspicion and education of family and referring physicians is needed to reduce the high risk of testicular loss.

Other Testicular Anomalies Associated with CryptorchidismSeveral rare anomalies of testicular development associated with cryptorchidism, each with 100-150 reported cases in the literature, include polyorchidism, splenogonadal fusion, and transverse tes-ticular ectopia. Because abdominal cryptorchidism commonly occurs in these cases, laparoscopy is useful in both diagnosis and treatment.

Polyorchidism is the presence of a supernumerary testis that is more commonly unilateral and on the left side, with rare cases of bilateral duplication or triplication reported in a comprehensive review of the pediatric and adult literature (Bergholz and Wenke, 2009). The cause is unknown, but most authors speculate that this anomaly is related to duplication or division of the genital ridge with or without the wolffian duct, as illustrated by Danrad and colleagues (2004). Testes are reported to be scrotal, inguinal, and abdominal in 75%, 20%, and 5% of cases, respectively (Kumar et al, 2008). Affected individuals are frequently asymptomatic, and the polyorchidism is identified at the time of orchidopexy or hernia repair, although a scrotal or inguinal mass and pain with or without torsion may occur and persistent müllerian remnants may coexist. Various classification schemes have been proposed, with a recent trend toward categorizing testes based on epididymal and vasal configuration (Bergholz et al, 2007; Khedis et al, 2008; Kumar et al, 2008). Kumar and colleagues (2008) suggest a clas-sification that differentiates between testes that are drained by a vas deferens: type A1—separate epididymis and vas, type A2—separate epididymis, and type A3—shared epididymis and vas from those with no vasal drainage: type B1—epididymis present and type B2—no epididymis or vas. This classification can aid in manage-ment decisions that should be based not only on the anatomy of the accessory ducts but also the position, size, and attachments of the testis. Observation and periodic self-examination without surgery should be considered for sonographically normal scrotal testes and orchidopexy for testes that are undescended but with intact ductal drainage (Spranger et al, 2002; Bergholz et al, 2007; Khedis et al, 2008). Occasional cases of testicular tumor have been reported in supernumerary testes, but it is unclear if this is a risk related to polyorchidism per se or to associated cryptorchidism or persistent müllerian duct syndrome (Spranger et al, 2002; Ghose et al, 2007).

Splenogonadal fusion is a defect characterized by continu-ous or discontinuous fibrous union between splenic tissue and the gonad, a condition much more commonly recognized in males (Khairat and Ismail, 2005). Approximately 30% of affected

number after 4 months of age in cryptorchid testes (Lackgren and Ploen, 1984; Rune et al, 1992; Regadera et al, 2001; Zivkovic and Hadziselimovic, 2009). Reduced expression of type IV collagen, a product of both Sertoli and myoid cells that may function in cell-cell communication, was reduced in basement membranes of undescended and contralaterally descended testes (Santamaria et al, 1990).

Impaired transformation of gonocytes to spermatogo-nia is reported in cryptorchid testes and may be a key determinant of fertility potential. In normal testes, germ cell number decreases after birth as gonocytes either degenerate by apoptosis or migrate to the basement membrane and differenti-ate into spermatogonia (Hadziselimovic et al, 1986; Huff et al, 2001). Although the ratio of gonocytes to spermatogonia appears to be normal in cryptorchid testes at about 1.5 months of age, delayed disappearance of gonocytes and appearance of adult dark (Ad) spermatogonia occurs in the undescended as compared with the contralateral descended testis. Ad spermatogonia are likely the reserve stem cells of the germ cell pool (Dym et al, 2009). The mechanisms involved in migration and/or differentiation of gonocytes into stem cells are not clearly defined but appear to involve ADAM-integrin-tetraspanin complexes, retinoic acid, platelet-derived growth factor receptor, and c-KIT (Culty, 2009). Hadziselimovic and colleagues hypothesize that failure of gonocyte differentiation in cryptorchidism reflects failure of post-natal activation of the HPG axis (Hadziselimovic et al, 1986); however, although they occur concurrently there are no data confirming a direct relationship between the two events.

Kollin and colleagues (2006, 2007) studied testicular growth in undescended and scrotal testes and measured the effect in orchi-dopexy on testicular size using serial ultrasonography in prospec-tive randomized studies. They showed that the undescended testis is not significantly smaller at birth but grows less well than the scrotal testis, and orchidopexy at age 9 months allows partial catch-up growth of the cryptorchid testis up to 4 years of age. In contrast, testes that remained cryptorchid until 3 years of age did not grow significantly before or after orchidopexy. The cellular components responsible for these differences in volume are not known. In scrotal testes, ethnic differences in testicular size as reported by Main and associates (2006b) were associated with increased inhibin-B levels and interpreted to primarily reflect dif-ferences in Sertoli cell number (Sharpe, 2006).

Anomalies of the Epididymis, Processus Vaginalis, and GubernaculumThe epididymis is often abnormal in boys with cryptorchidism (Marshall and Shermeta, 1979), with a reported frequency of 35% to 75% (Heath et al, 1984; Gill et al, 1989; Mollaeian et al, 1994). Anatomic findings in decreasing order of frequency include anomalies of fusion between the caput and/or cauda epididymis, elongation and/or looping, and atresia. The occurrence of epididy-mal anomalies correlates with both the severity of cryptorchidism and the degree of closure of the processus vaginalis (Elder, 1992; Barthold and Redman, 1996). The degree to which these anoma-lies contribute to the risk of subfertility in males with a history of cryptorchidism remains undefined. Similarly, failure of closure of the processus vaginalis and attachment of the gubernacular remnant are common in association with cryptorchidism. In their study of 759 patients, Cendron and colleagues (1993) identified a persistently patent processus vaginalis ipsilateral to 87% of unilat-eral and 71% of bilateral undescended testes. Specific notation of the gubernacular position available from this and another large


position is marginal, until a year of age may be warranted. However, even if spontaneous descent occurs, continued observation is needed because of the risk for recurrent cryptorchidism, or “re-ascent” of a spontaneously descended testis.

Recently, two groups from the Netherlands published reports of the outcome of boys with acquired undescended testes who were observed expectantly (Sijstermans et al, 2006; Eijsbouts et al, 2007). These authors reported spontaneous descent in 75 of 132 (57%) and 98 of 129 (75%) testes, respectively, most by mid puberty. The mean volume of descended testes in the study by Eijsbouts and coworkers was closer to those of normal contralateral testes as compared with boys who underwent orchi-dopexy. However, in both of these series high scrotal testes comprised the majority and of those that descended and low scrotal “unstable” testes (likely retractile) were also included. On the other hand, Eijsbouts and coworkers reported that 19 of 82 unilateral cases had previous contralateral orchidopexy and that 10 boys required orchidopexy because of clinical hernia, pain, or torsion, suggesting a higher likelihood of true cryptorchidism in these cases. Because these studies were not randomized and provide no long-term data regarding testicular outcome, observation is not recommended for acquired cryptorchidism.

Medical TherapyHormonal therapy has been used for a variety of indications in patients with cryptorchidism, including differentiation of retrac-tile from true undescended testes, stimulation of testicular descent or germ cell maturation, and as an adjunct to abdominal orchido-pexy. These therapies may be used sporadically, but none is con-sidered the standard of care, likely because of limited availability of some medications, lack of rigorous data supporting their effi-cacy, and concerns about possible adverse effects (Thorsson et al, 2007).

Several published reports address the usefulness of hormonal therapy in distinguishing retractile from true undescended testes. In prospective series reporting the response of putative retractile testes to hCG, success rates vary from 58% to 100% and may be dependent not only on age, degree of retractility, and accuracy of diagnosis but also on the dosage regimen used (Rajfer et al, 1986; Miller et al, 2003; Metin et al, 2005). In patients treated by Miller and associates (2003), nonresponders undergoing surgery had typical findings associated with true cryptorchidism, including a patent processus vaginalis and superficial inguinal pouch location, and follow-up was short (6 to 12 months). These data suggest that hCG fails to reliably distinguish retractile from cryptorchid testes and therefore does not eliminate the need for serial examinations in these patients.

LH-releasing hormone (LHRH) and/or hCG have been used as hormonal therapy to induce descent of testes for more than 70 years based on the premise that androgens promote testicular descent, but the efficacy of this therapy is questionable (Pyorala et al, 1995; Henna et al, 2004; Thorsson et al, 2007). Even when analysis is limited to randomized, placebo-controlled trials the reliability of the data is limited in that many series did not confirm exclusion of retractile or nonpalpable (potentially absent) testes, adequacy of randomization procedures, and/or long-term efficacy of the treatment. Although the efficacy of either hormonal treat-ment is about 20% and superior to placebo in randomized trials, this effect is not clearly clinically significant. Although lower tes-ticular position shows a clear correlation with response to therapy, no consistent differences in response based on age or laterality

individuals have cryptorchidism, with the majority of cases abdominal and bilateral (59%) and 65% and 26% involving the left and right sides, respectively (Cortes et al, 1996). The continu-ous form of splenogonadal fusion is more commonly syndromic, associated with limb defects, micrognathia, microglossia, anal atresia, and pulmonary hypoplasia (McPherson et al, 2003), whereas cryptorchidism is associated with both continuous and discontinuous forms and most commonly coexists with bilateral amelia (Cortes et al, 1996). The pathogenesis of the anomaly is not understood but based on the constellation of defects observed is hypothesized to represent a developmental field defect with aberrant migration of spleen cells occurring at 5 to 8 weeks’ gesta-tion. Most cases present incidentally at the time of orchidopexy or inguinal hernia repair or with scrotal swelling related to illness-related reactive changes within the splenic tissue. Testicular malig-nancy is reported rarely in association with cryptorchidism and not likely related to the splenic anomaly. Treatment should focus on recognition of the defect at the time of orchidopexy and avoid-ance of unnecessary orchiectomy.

Transverse testicular ectopia may occur as an isolated anomaly in otherwise normal males with cryptorchidism or van-ishing testes or be associated with persistent müllerian duct syn-drome in 20% to 50% of cases (De Luna et al, 2003; Wuerstle et al, 2007; Thambidorai and Khaleed, 2008). The classic presentation is inguinal hernia with contralateral nonpalpable testis, although both testes may be palpable in the same hemiscrotum. The etiol-ogy may be related to mechanical hindrance to descent by fusion of wolffian duct derivatives (Chacko et al, 2006) or persistent mül-lerian ducts or to a primary gubernacular defect. Interestingly, complete loss of the gubernacular attachment, transverse ectopia, and/or torsion were observed in transgenic mice null for Insl3 (Nef and Parada, 1999; Zimmermann et al, 1999). Orchidopexy may be performed using open surgical or laparoscopic techniques, but in cases of vasal fusion the involved testis is mobilized ipsilaterally and a transseptal approach is used to place the testis in the con-tralateral scrotum (Chacko et al, 2006; Thambidorai and Khaleed, 2008).

TreatmentCorrection of cryptorchidism is indicated to optimize testicular function, potentially reduce and/or facilitate diagnosis of testicular malignancy, provide cosmetic benefits, and prevent complications such as clinical hernia or torsion. Except in certain cases of associated complex medical illness or in the postnatal period, treatment should proceed after confirmation of the diagnosis. A flow diagram (Fig. 132–4) shows the recommended approach to palpable and nonpalpable testes in patients confirmed to have undescended testis by an experienced examiner.

In infants, observation is indicated for the first 6 postnatal months to allow spontaneous testicular descent. If descent does not occur in the postnatal period, present consensus supports surgical treatment at 6 months of age. Support for this approach is based on the following rationale: (1) descent is unlikely in full-term males after age 6 months (Wenzler et al, 2004); (2) testicular growth is restored after early orchidopexy (Kollin et al, 2007); (3) hormone therapy is not considered effica-cious (Ritzen et al, 2007); and (4) orchidopexy for abdominal testes may be facilitated in young infants soon after the hormonal surge. In boys with a history of prematurity, spontaneous descent may be delayed and therefore continued observation for 6 months beyond the expected date of delivery or, especially if testicular


lack of large prospective studies, it is unclear if hormone therapy for cryptorchidism is beneficial or harmful to germ cells in the short or long term.

Hadziselimovic and colleagues (1987b) have advocated use of low-dose, long-term (every other day for 6 months) LHRH ana-logue (buserelin) therapy for stimulation of germ cell development in conjunction with orchidopexy. In a retrospective study of non-randomized, non–age-matched patients receiving buserelin versus surgery only, S/T counts were significantly higher in the treated group. A subset of patients from this same cohort with the most severe testicular histology underwent rebiopsy after completion of therapy and were compared with a group of 8 boys of unknown age who required reoperative orchidopexy (Hadziselimovic et al, 1987a). A significant improvement in mean S/T ratio was seen in the buserelin-treated but not the surgical group. Similarly, in a smaller select group of boys treated with low doses of a related LHRH agonist, nafarelin, improved histology was observed in one or both testes at rebiopsy in 8 of 12 boys. In a randomized study of clinically matched boys receiving buserelin and hCG, placebo and hCG, or surgery alone (19 to 25/group), S/T counts were also significantly higher in those treated with buserelin (Bica and Hadziselimovic, 1992). More recently, Hadziselimovic (2008) published a nonrandomized retrospective study showing that

have been reported in randomized trials. Overall, the evidence from rigorous studies indicates that LHRH therapy for cryptorchidism is only marginally more effective than placebo; although not studied in randomized placebo-controlled trials because of its route of administration, hCG also shows limited efficacy. Other uses of hCG including treatment of acquired cryptorchidism and to facilitate palpability and/or treatment of the abdominal testis (Polascik et al, 1996; Baker et al, 2001; Bukowski et al, 2001) also have limited efficacy.

The question of the effect of therapeutic doses of hCG or LHRH on germ cell development has been addressed in several conflict-ing studies that are limited by small sample size, absent or subop-timal randomization, and variable availability of biopsy data (Ong et al, 2005). In small, retrospective studies, hCG treatment was associated with increased germ cell apoptosis at biopsy and lower adult testis volume (Dunkel et al, 1997) and previous hCG or LHRH therapy was associated with reduced S/T counts in 1- to 3-year-old boys as compared with surgery alone (Cortes et al, 2000). In contrast, Schwentner and associates randomized young boys (mean age 33 months, 21 per group) to LHRH or no hor-monal therapy before surgery and reported that mean S/T count was higher (1.05 ± 0.71) in LHRH-treated as compared with non-treated (0.52 ± 0.39) testes (Schwentner et al, 2005). In view of a

Figure 132–4. Algorithm for management of the undescended testis. This is the recommended approach to diagnosis and treatment of palpable and nonpalpable testes in patients confirmed to have undescended testis by an experienced examiner. F/U, follow-up; PV, processus vaginalis; US, ultrasonography.

Palpable

Testis examination byexperienced observer

Nonpalpable

RetractileConsider US• Overweight• Uncooperative

Yearly exams andparental observation

Large contralateraltestis >2 SDNo palpableappendage

Normal contralateral testisNo intrascrotal structures

Inguinal orchidopexywith or w/o hernia repair

Long-term F/UCounseling the family

and self-exam

LaparoscopyScrotal nubbin

Orchidopexy ? Bilateral OrchiectomyConsider stagedapproach

Scrotalexcision

Considercontralateral

testicularfixation

No furtherintervention

Counsel familyabout prosthesis

Viabletestis

Laparoscopicorchidopexy

1- or 2-stageFowler-Stephens

orchidopexy

Hypotrophic, shortvas, dysgenetic, or

postpubertal

Considermicrovascularorchidopexy

Inguinalexploration

Solitarytestis

Nearring

Highabdominal

? Atretic vesselsVanishing testis

Vessels passinternal ring

Abdominaltestis

? Inguinalrepair

Patent PV

Distal to external ring Considerscrotal

orchidopexy


brought to dependent scrotal position after these maneuvers and a two-stage procedure may be considered as an alternative to orchiectomy, which is preferentially reserved for grossly abnormal or atrophic testes. Dessanti and associates (2009) describe a novel two-stage technique for high canalicular or abdominal testes that involves placement of a polytetrafluoroethylene membrane around the mobilized cord, fixation of the testis to the invaginated scrotum with a pledget, followed by a 9- to 12-month delay that allowed spontaneous scrotal localization of the testis in 82% of 45 testes.

A large clamp or a finger can be used to create a tunnel just anterior to the pubis and a scrotal or subdartos pouch created after transverse incision of the scrotal skin (Ritchey and Bloom, 1995). The testis is passed through an opening in the dartos without twisting of the spermatic cord. Existing appendages should be excised and the epididymis inspected and any anoma-lies recorded. Recording of testicular volume by direct caliper measurement in three dimensions and similar (estimated) mea-surements of contralateral testicular volume can establish a base-line for postoperative assessment. Secure fixation of the testis within the pouch can be achieved by tension-free closure of the opening in the dartos around the cord, incorporating the cut edge of the tunica vaginalis. If needed, additional absorbable fixation sutures can be placed between the visceral tunica vaginalis and the dartos. Sutures through the tunica albuginea of the testis are not recommended because of possible injury to the testis via inflammatory or vascular insult; suture fixation of the testis is in any event not needed if mobilization is adequate and a subdartos pouch technique is used. Closure is completed with absorbable sutures. Supplemental local or regional techniques for periopera-tive pain control are advisable and may include local anesthetic infiltration or caudal anesthesia; the latter is particularly useful in younger patients undergoing bilateral inguinal or concomitant penile surgery.

Testicular biopsy has been performed routinely in some centers and is advocated by Hadziselimovic and colleagues (2007) as a method to determine prognosis for fertility. This approach is con-troversial and not recommended outside of research protocols because it does not change the current approach to treatment (Ritzen et al, 2007; Beckers and van der Horst, 2008). The risk to the cryptorchid testis from biopsy is theoretical; although long-term effects do not appear to include increased risk of microlithia-sis or antisperm antibody formation (Patel et al, 2005), other more subtle effects cannot be excluded from the available data. Biopsy is indicated in cases of sexual ambiguity or if clinical evidence of testicular dysgenesis is present.

A minimum of 6 months’ follow-up is needed to determine testis position and size once stabilized, and long-term follow-up is indicated for counseling of the patient regarding fertility issues, risk of testicular malignancy, and self-examination. Complications of inguinal orchidopexy for a palpable testis are uncommon; those of greatest frequency and concern include testicular retraction or atrophy. In a comprehensive literature review in 1995, Docimo (1995) concluded that the overall risk of atrophy or nonscrotal position was approximately 15% overall in published reports, sig-nificantly higher in abdominal or peeping testes (24%) compared with those distal to the internal ring (10%) and higher in boys operated after 6 years of age. Torsion of a scrotal testis after orchi-dopexy has been reported but is very rare, and the risk may be minimized by using a subdartos pouch. If complete intrascrotal testicular atrophy occurs postoperatively, further intervention is not needed but the option of testicular prosthesis placement should be offered to the patient and family (Bodiwala et al, 2007).

buserelin-treated males (most also received hCG) with a history of unilateral cryptorchidism and poor pretreatment S/T counts had much higher sperm counts than patients who underwent surgery only (n = 15 per group). Unfortunately, these two groups were small and not clinically matched prospectively to limit other potential confounding factors, such as testicular position, and sperm counts in the surgery-only group were lower than typical for unilateral cryptorchidism. Overall, these studies provide pre-liminary, suggestive evidence that buserelin may have both short- and long-term effects on testicular histology and/or fertility potential. However, the suboptimal design of the studies on which this evidence is based mandates that future well-designed prospec-tive studies are necessary before routine use of buserelin treatment in cryptorchidism.

In summary, little if any high-quality evidence exists showing a benefit of hormonal therapy for cryptorchidism or for stimula-tion of germ cells. A recent statement by the Nordic Con-sensus group recommends that testicular biopsy and hormonal therapy not be used in standard clinical care of boys with cryptorchidism (Ritzen et al, 2007), although not all clinicians concur (Hadziselimovic and Zivkovic, 2007).

Surgical Approach to the Palpable TestisThe standard treatment for palpable testes is inguinal orchidopexy with repair of an associated hernia if present (Hutcheson et al, 2000a), although in recent years a primary scrotal approach as originally described and advocated by Bianchi and colleagues (Bianchi and Squire, 1989; Iyer et al, 1995) has been advocated by some. The recommended age for surgical intervention has gradu-ally declined over the years and presently is age 6 months in full-term males in whom the testes have failed to descend. However, the average age of orchidopexy remains about 4 years in many series, likely owing to the frequency of milder “acquired” cases as well as delayed referral of some cases diagnosed at birth (Barthold and Gonzalez, 2003). An option for pubertal and postpubertal boys is orchiectomy, especially if the testis is abdominal or difficult to mobilize because poor spermatogenesis and hypotrophy are usually present and the risk of carcinoma in situ and torsion exist (Rogers et al, 1998).

Inguinal Orchidopexy. After induction of anesthesia, the patient is reexamined to confirm that the testis is palpable and to identify the lowest testicular position. In the standard inguinal approach, a low transverse incision in Langer’s lines at or below the inguinal crease is made superolateral to the pubic tubercle. Dissection of the subcutaneous tissue should include a search for a testis within the superficial inguinal pouch. The external oblique fascia is incised to expose the canal with care to avoid injury to the ilio-inguinal nerve. Testis position is recorded relative to the inguinal canal. The spermatic cord is isolated, and the testis is dissected distally to its attachment to the gubernacular remnant. Transec-tion of the gubernaculum distal to the sac will avoid potential injury to a long-looping vas. Longitudinal incision of the internal spermatic fascia allows free mobilization of an intact hernia sac, if present, and minimizes skeletonization of the vas and spermatic vessels. After transection, the sac is mobilized to the level of the internal inguinal ring and suture ligated. Incision of the internal spermatic and transversalis fascia at the level of the ring facilitates additional retroperitoneal mobilization of the vas and vessels, if needed. Further maneuvers to provide spermatic cord length include transection of lateral fascial bands along the cord, cranial retroperitoneal dissection, medial transposition of the testis beneath the epigastric vessels (Prentiss maneuver) and, if required, cranial extension of the incision. Very rarely, the testis cannot be


spermatic vessel transection. Orchiectomy is appropriate for patients with testes that are poorly viable and/or at higher risk for tumor, such as very small or dysgenetic prepubertal or in postpu-bertal patients, and is best performed laparoscopically.

Open Transabdominal Orchidopexy. Extensive dissection of the vas and vessels is facilitated by a longitudinal opening of the internal oblique and peritoneum through an extended inguinal incision (Kirsch et al, 1998) or via a higher incision medial to the pubic tubercle and a preperitoneal approach (Gheiler et al, 1997; Jones and Bagley, 1979). In the procedure described by Jones and Bagley the internal ring is approached via a muscle-splitting inci-sion, the peritoneum is opened, the testis is delivered, and the vas and vessels are freed from their peritoneal attachments. A tunnel is created to the scrotum, and the testis is secured in place as for an inguinal orchidopexy. The reported success rate for this proce-dure for abdominal testes was 95% (Gheiler et al, 1997).

Laparoscopic Orchidopexy and Fowler-Stephens Orchidopexy. Operative laparoscopy emerged over 15 years ago as the procedure of choice for abdominal orchidopexy (Caldamone and Amaral, 1994; Jordan and Winslow, 1994), and the basic surgical approach and high success rates have stood the test of time (Table 132–1). The feasibility of primary versus Fowler-Stephens orchidopexy depends on the length of the vas and vessels, presence or absence of looping ductal structures, and age of the patient. Although laparoscopy allows the surgeon to assess some of these features before choosing a specific surgical procedure, the choice may be difficult (Yucel et al, 2007). Observed testicular position alone may correlate poorly with the ultimate length of the cord after mobilization.

After induction of anesthesia, a further attempt to palpate the testis is made, although a laparoscopic approach may be consid-ered for mobilization of high canalicular testes as well. After decompression of the bladder and stomach, an infraumbilical 5-mm trocar is placed for passage of a 30-degree lens and both internal rings are visualized. An open Hasson or Bailez technique is preferable for umbilical trocar placement in the pediatric age group to minimize the risk of injury (Franc-Guimond et al, 2003). CO2 pneumoperitoneum to a maximum pressure of 8 to 12 mm Hg is used. The size and position of the testis within the abdomen is determined before further decision making. For single-stage lapa-roscopic orchidopexy, additional 2- or 3-mm trocars are placed in the right and left lower quadrants to triangulate with the umbili-cus and ipsilateral internal ring or in the midclavicular line at the level of the umbilicus bilaterally. The major steps are mobilization of any structures extending distal to the internal ring, including epididymis/vas and gubernacular remnant, transection of the peri-toneum lateral to the vessels and distal to the vas, and proximal mobilization of the vessels while maintaining collateral blood supply between the vas and spermatic vessels if a Fowler-Stephens maneuver becomes necessary. Samadi and associates (2003) advo-cate initial mobilization of the gubernaculum to be used as a handle for further mobilization of the testis, and minimal use of cautery during this maneuver. Ability to mobilize the testis to the opposite internal ring has been used as a measure of adequate length for placement in the scrotum but is not predictable in some series. Once mobilized, the testis is brought through a new hiatus at the level of the medial umbilical ligament or through the exist-ing internal inguinal ring. This maneuver can be completed using a transscrotal clamp or port. With tension on the extra-abdominal testis, peritoneal attachments overlying the cord can be more easily transected, thus providing additional length. In some cases the testis can only be brought into the upper scrotum; the long-term adequacy of this approach is not clear. Excessive tension on

Implantation of a testicular prosthesis should occur at least 6 months after any inguinoscrotal procedure or after puberty and is best performed through an inguinal approach. Closure of the scrotal fascia above the implant using a purse-string nonabsorb-able suture is required. Risks including displacement, pain, or infection occur in less than 5% of cases. Clinical experience sug-gests that cryptorchid boys may request prosthesis implantation less frequently than males with acute testicular loss after puberty (Bodiwala et al, 2007). Elder and associates (1989) recommended that prepubertal prosthesis placement be considered, but it is not clear whether this approach is preferable to placement after puberty.

Reoperation is indicated if a testis is nonscrotal after orchido-pexy. If the testis is prescrotal, a primary scrotal approach can be considered and may allow adequate mobilization of the testis. If inguinal exploration is needed to provide sufficient cord length, several approaches are available. Redman (2000) described a useful technique for primary or secondary orchidopexy that involves a lateral approach to the cord after mobilization of the external oblique and cremaster fasciae. This approach avoids traversal of the previously scarred layers anterior to the cord and a clearer view of the anatomy. Cartwright and colleagues (1993) described mobi-lization of the intracanicular cord with an overlying patch of external spermatic fascia. The importance of correcting a persis-tently patent processus vaginalis and/or of adequate retroperito-neal mobilization of the cord in cases of high recurrent cryptorchidism has been stressed (Redman, 2000; Pesce et al, 2001; Ziylan et al, 2004). The results of secondary orchidopexy appear to be similar to the primary procedure, although the risk of vascular and vasal injury is theoretically higher (Pesce et al, 2001).

Transscrotal Orchidopexy. A primary scrotal approach can be considered when the testis is palpable (Bianchi and Squire, 1989; Iyer et al, 1995), although some surgeons reserve this approach for testes that are close to or can be drawn into the scrotum (Russinko et al, 2003; Rajimwale et al, 2004; Bassel et al, 2007; Takahashi et al, 2009). An incision along the superior scrotal border is made and the distal sac and overlying cremaster mobi-lized. Once dissected free, the sac can be placed on traction and freed as far cranially as possible, “high above the inguinal canal” (Iyer et al, 1995), although some cases require conversion to an inguinal approach (Parsons et al, 2003; Dayanc et al, 2007). Rajimwale and coworkers confirmed in several cases that the hernia sac had been effectively ligated above the internal ring via the scrotal incision when a secondary inguinal incision was required for further mobilization of the testis (Rajimwale et al, 2004). Fixation sutures through the tunica albuginea were used in many series of scrotal orchidopexy (Jawad, 1997; Russinko et al, 2003; Bassel et al, 2007; Dayanc et al, 2007; Takahashi et al, 2009). The risk of testicular retraction or atrophy was reported as 0% to 2% in most of these series after follow-up ranging from 1 month to 3 years. However, postoperative hernia was reported in about 3% of cases in two series containing a larger proportion of cana-licular testes (Dayanc et al, 2007; Al-Mandil et al, 2008) and in 2% of hernias repaired by Bianchi’s group using a scrotal approach (Iyer et al, 1995). Although the risk of this complication appears low, follow-up is not sufficient in reported series to fully define the risk.

Surgical Approach to the Abdominal TestisOnce an abdominal testis has been identified by laparoscopy or other means, a decision is made whether to proceed with an open or laparoscopic, one- or two-stage orchidopexy with or without


For testes that are not near (variably defined as 2 to 4 cm above) the internal inguinal ring, transection of the spermatic vessels as originally described by Fowler and Stephens (1959) may be neces-sary; a long-looping vas facilitates but is not required for testicular mobilization to the scrotum. The Fowler-Stephens procedure is now typically performed laparoscopically with spermatic vessel clipping (Bloom, 1991) followed by laparoscopic or open testicular mobilization 6 months later or in one stage. Although most sur-geons transect the spermatic vessels 1.5 to 3 cm above the testis, Koff and Sethi (1996) proposed that ligation close to the testis is preferable. This group subsequently studied the effect of low versus high transection of the vessels in prepubertal rats and showed a reduction in adult testicular sperm numbers that was similar in both groups (Srinivas et al, 2005). In human studies, testicular biopsies before and after spermatic vessel transection also showed a reduction in S/T count, a finding that was signifi-cant in younger boys (Thorup et al, 1999; Rosito et al, 2004). In general, the preferred approach is avoidance of spermatic vessel transection whenever possible; the available data suggest this is

the vessels during placement of the testis should be avoided, however, because injury or avulsion of the spermatic vessels may occur (Esposito et al, 2002). A key strategy should be preservation of the blood supply between the vas and spermatic artery during dissection so that the Fowler-Stephens procedure can be performed if necessary.

Formal closure of the dissected internal ring, irrespective of whether the mobilized testes passes through it, does not appear to be necessary (Handa et al, 2005; Riquelme et al, 2007); indeed, previous experience with open hernia repair suggests that ligation is not needed if the internal ring is dissected (Mohta et al, 2003). A contralateral patent processus vaginalis was identified in 9% of boys undergoing laparoscopic orchidopexy in one series (Palmer and Rastinehad, 2008), and laparoscopic repair was performed and recommended. The necessity for this approach in preventing clini-cal hernia formation is questionable based on studies of boys undergoing laparoscopic or open contralateral hernia repair (see Schier, 2007b, and discussion in the later section Hernias and Hydroceles).

Table 132–1. Results of Laparoscopic Orchidopexy*

PROCEDURE SERIESPATIENTS (TESTES) AGE FOLLOW-UP HIGH POSITION ATROPHY

OVERALL SUCCESS

Laparoscopic orchidopexy

Baker et al, 2001 178 (208) 36 mo 7.7 mo (mean) 0.6%†

(1/178)2%

(4/178)97%

Samadi et al, 2003 139 ? ≥6 mo 3%†

(4/139)0 97%

Handa et al, 2005 58 (76) ? 2.2 yr (median) 0† 3%(2/65)

97%

El-Anany et al, 2007 46 5 yr 3 yr (mean) 9%(4/46)

0 90%

Kaye and Palmer, 2008 19 (38) 9 mo (median) 6-12 mo 18%(7/38)

0 82%

Yucel et al, 2007 34 ~12 mo (median) 5-8 mo (median) 19%(6/32)

16%(5/32)

65%

Radmayr et al, 2003 28 (28) 1.9 yr 6.2 yr 0 0 100%Denes et al, 2008 24 (26) 6.4 yr ≥6 mo 0† 4%

(1/26)96%

Esposito et al, 2002 25 (25) 3.9 yr (median) 23 mo (median) 0 4%(1/25)

96%

Laparoscopic one-stage FS

Esposito and Garipoli, 1997 33 (33) 3-10 yr (range) 30 mo (mean) 0 3%(1/33)

97%

Baker et al, 2001 25 (28) 31 mo 8.6 mo (mean) 7%†

(2/27)22%

(6/27)71%

Chang et al, 2001 20 1.5 yr (median) ≥6 mo 0† 16%(3/19)

84%

Laparoscopic two-stage FS

Baker et al, 2001 63 (74) 55 mo 20 mo 2%†

(1/58)10%

(6/58)88%

Lotan et al, 2001 59 (66) 14 mo 3-12 mo ? ? 84%El-Anany et al, 2007 47 5 yr 3 yr (mean) 0 4%

(2/47)96%

Radmayr et al, 2003 29 (29) 1.9 yr 6.2 yr (mean) 0 7%(2/29)

93%

Robertson et al, 2007 21 (25) 36 mo (mean) 6 & 18 mo 0† 14%(3/21)

86%

Denes et al, 2008 15 (21) 6.4 yr ≥6 mo 0† 14%(3/21)

88%

Hay et al, 1999 20 ? ≥6 mo 25%(5/20)

15%(3/20)

60%

*Reported results of abdominal, one- and two-stage Fowler-Stephens (FS) orchidopexy in.series with at least 20 treated testes. Age is mean for entire series unless otherwise noted. High position refers to testes not in dependent scrotal position.

†Position within scrotum not clearly documented. Overall success refers to the frequency of nonatrophic testes in satisfactory scrotal position according to criteria used by the authors.


of formerly unilaterally cryptorchid men. The limited available data comparing earlier (age < 9 years) and later treatment did not show differences in the frequency of subfertility after unilateral (281 cases) or bilateral (123 cases) orchidopexy. Similarly, subset analysis failed to identify any effect of hCG treatment. Two sub-sequent large studies of semen parameters in men who underwent orchidopexy in childhood also found differences between bilateral and unilateral cryptorchidism but less consistent overall results. Okuyama and associates (1989) reported normal sperm density in 0%, 72%, 77%, and 42% of men after bilateral orchidopexy (61 patients), unilateral orchidopexy (149 patients), unilateral orchi-ectomy (26 patients), and no treatment (38 patients) for inguinal testes without hormone therapy. All of these subjects had three semen analyses. In contrast, Gracia and colleagues (2000) reported normal semen samples in 10 of 55 (18%) men with a history of bilateral and 57 of 171 (33%) men with previous unilateral crypt-orchidism. The majority of testes in this series were canalicular, and 80% of subjects received preoperative hCG therapy. These authors noted no differences based on testicular position, and semen quality was not correlated with age of surgery in either series. In a cohort of 91 patients with unilateral cryptorchidism who underwent orchidopexy after the onset of puberty (age 14 to 29), the risk of azoospermia or oligospermia was 84% (Grasso et al, 1991), a trend in keeping with the data reported previously (Okuyama et al, 1989). Puri and O’Donnell (1988) studied 142 men who underwent unilateral (119 men) or bilateral (23 men) orchidopexy at age 7 years or older and reported normal sperm density in 84% and 50% of cases, respectively.

Mean S/T counts obtained at biopsy show correlation with long-term fertility potential as measured by mean semen analysis parameters in series but may not be predictive in individuals (Engeler et al, 2000; Cortes et al, 2003a; Rusnack et al, 2003). Other data suggest a better correlation between the number of Ad spermatogonia in cryptorchid testes and sperm count in adult-hood after previous unilateral or bilateral orchidopexy with or without prior hormonal therapy (Hadziselimovic et al, 2007; Hadziselimovic and Hoecht, 2008). In non–hormonally treated cases, total sperm count was normal (>40 million/ejaculate) in 84% of 25 men with Ad spermatogonia present in both testicular biopsy specimens, whereas it was subnormal in all 18 men (10 of the 19 men in this series had a history of bilateral cryptorchidism) in whom biopsies were negative for Ad spermatogonia. Total germ cell counts were reportedly not predictive of sperm concentration in this series (Hadziselimovic and Hoecht, 2008). Both Ad sper-matogonia count and germ cell absence appear promis-ing as measures of fertility prognosis, but their predictive value has not been confirmed in additional studies to date. Further prospective studies of these parameters are indicated.

Outcome studies of semen analysis in men with a history of cryptorchidism are believed to provide useful information that predicts fertility potential. However, a large population study of fertile and infertile men with fertile partners suggests that there is large overlap between semen parameters in men with and without proven paternity (Guzick et al, 2001). In this study, the authors established lower infertile threshold levels for density (13.5 × 106/mL), motility (>35%), and normal morphology (>9%) than had been established by World Health Association criteria. About 3% of fertile men in this series had a sperm density of less than 10 × 106/mL, and measurements between 13.4 and 48 × 106/mL were considered indeterminate. Repeated semen analyses, rarely obtained in studies of formerly cryptorchid men, are needed to provide reliable data in normal men (Oshio et al, 2004).

possible in the majority of cases of abdominal orchidopexy. In rare cases, particularly if the testis is retrovesical, the vas is too short to allow scrotal placement of the testis and orchiectomy is ulti-mately required (Perovic and Janic, 1997).

The success rates for laparoscopic procedures as shown in Table 132–1 (Jordan and Winslow, 1994; Esposito and Garipoli, 1997; Hay et al, 1999; Baker et al, 2001; Lotan et al, 2001; Esposito et al, 2002; Radmayr et al, 2003; Samadi et al, 2003; Handa et al, 2005; Robertson et al, 2007; Yucel et al, 2007; Chang and Franco, 2008; Denes et al, 2008; Kaye and Palmer, 2008) appear to compare favorably with the corresponding 74%, 63%, and 77% overall success rates for open surgical and one- and two-stage Fowler-Stephens procedures, respectively, reported by Docimo (1995). Variation in reported results in these series may reflect inherent selection bias due to differences in patient age, testicular position, length of follow-up, and/or criteria used to define success, such as “intrascrotal” versus “dependent scrotal” position. Some authors recommend that ultrasound be used to confirm testicular viability postoperatively (Esposito et al, 2002). Other complications of laparoscopic orchidopexy appear to be rare and potentially include bladder or vascular injury, hypercapnia, and delayed small bowel obstruction (Esposito et al, 2003; Hsieh et al, 2009).

Laparoscopic techniques may be applicable in unusual cases, including bilateral orchidopexy, abdominal wall defects, polyor-chidism, splenogonadal fusion, and transverse testicular ectopia with or without persistent müllerian ducts. Many authors recom-mend simultaneous bilateral abdominal orchidopexy (Kaye and Palmer, 2008), but the surgeon should consider a staged approach if both testes are very high or the viability of a testis is questioned during the course of orchidopexy. Depending on the outcome of the first procedure at 6 months’ follow-up, the surgeon can choose an operative approach to the contralateral side that would appear to minimize the risk of bilateral testicular atrophy (Thorup et al, 2007). Some surgeons have considered microvascular orchidopexy to be a preferred approach to the solitary abdominal testis, par-ticularly with historical success rates of 88% as compared with lower rates for open procedures (Docimo, 1995). At a center with substantial experience using the microvascular approach, long-term success rates of 96% for standard and 88% for laparoscopi-cally assisted autotransplantation were reported (Bukowski et al, 1995b; Tackett et al, 2002). The advantage of this approach is preservation of the spermatic vessels, at the cost of longer opera-tive time and requirements for an experienced microvascular surgeon and hospital stay.

PrognosisRisk of SubfertilityAlthough there is strong evidence that a history of cryptorchidism is associated with subfertility in individual patients, the effects of age at diagnosis, type of treatment, and/or severity of disease on outcome remain incompletely defined. Major limitations in the interpretation of cryptorchidism outcome studies include selec-tion bias due to incomplete follow-up of large patient cohorts, heterogeneity of diagnosis and timing/type of treatment, and other methodologic concerns, including lack of age-matched con-trols, failure of abstinence before semen analysis, and/or analysis of a single semen sample. In a large review of retrospective studies published in the 50 previous years that did not take these concerns into consideration and did not include a statistical meta-analysis, Chilvers and colleagues (1986) reported overall rates of oligosper-mia and/or azoospermia in 75% of formerly bilaterally and 43%


majority of cases, but the duration and severity of retractility was poorly documented in these series. These studies do not provide sufficient evidence for infertility risk in uncomplicated cases of retractile testis. Two series reported varying degrees of abnormal germ or Sertoli cell development in retractile testes of boys who underwent elective orchidopexy as compared with boys with descended testes; differences were qualitatively similar to findings in cryptorchid testes (Hadziselimovic et al, 1987a; Cinti et al, 1993). However, small sample size per subgroup limits interpreta-tion of these data. Han and associates (1999) compared 61 retrac-tile with 83 cryptorchid testis biopsies and noted similar trends but did not include a control group. In a retrospective series of 45 adults with spontaneous descent of bilaterally undescended testes after age 10 by history, Brenholm Rasmussen and coworkers (1988) observed testicular volumes of less than 15 mL in 62% and sperm counts below 20 million/mL in 44% of patients. Large, prospective studies of persistently retractile testes and cases of acquired crypt-orchidism are needed to better define diagnosis and prognosis in these groups of patients.

In summary, available data provide strong evidence that fertility potential is compromised in men with a history of bilateral cryptorchidism but the frequency of abnormal hormonal and sperm parameters in unilateral cases is higher than the relative risk of infertility as measured by paternity data. Unfortunately, the number of formerly bilaterally cryptorchid men who have been comprehen-sively studied is limited. Although data suggest some association between age at surgery or hormone therapy and risk of infertility, further studies are needed to elucidate the relationships between these factors.

Risk of MalignancyThe increased risk of testicular germ cell tumor (TGCT) in males with a history of cryptorchidism has been known for many years. Both seminoma and nonseminomatous germ cell tumors (NSGCT) develop from carcinoma in situ (CIS) of the testis, also called intratubular germ cell neoplasia, unclassified (ITGCNU), and are believed to be developmental in origin (Rajpert-de Meyts and Hoei-Hansen, 2007). The hypothesis that persistent gonocytes are the precursors of testicular CIS has existed for some time, and recent gene expression data indeed support a common origin for the two cell types (Sonne et al, 2009). The histologic data suggest-ing that gonocytes fail to transform normally in cryptorchid testes may coincide with eventual transformation of these persistent cells into CIS and TGCT. However, to date no evidence directly links germ cell maldevelopment in individual patients to eventual malignant transformation. Using placenta-like alkaline phospha-tase (PLAP) as a marker of ITGCNU, Engeler and associates (2000) identified PLAP-positive cells in 5% of 440 patients, most (82%) younger than 3 years of age, who had undergone testicular biopsy and orchidopexy several years earlier. Whereas up to 50% of adults with ITGCNU are expected to develop TGCT over time, no tumor was detected in the 15 of 22 affected individuals that the authors were able to evaluate a median of 21 years later. However, PLAP immunopositivity may be a normal finding in infants during the first year of life (Jorgensen et al, 1993). Similarly, Cortes and coworkers (2003b) identified multinucleated spermatogonia in 13 (8%) of 163 consecutive patients undergoing biopsy at the time of orchidopexy. This finding occurred in younger boys and was associated with an S/T count that was usually normal and higher than the mean for the majority of cases. Although not identified in normal boys, the relevance of this finding to tumor risk remains completely unknown.

Consequently, determination of paternity status is an alternative measure of fertility that should be considered when determining prognosis. Limitations of this approach include paternal discrep-ancy and variability in the timing and degree of interest in attempts at paternity. Although of concern and not ethically retrievable, a recent review (Bellis et al, 2005) found that the median level of paternal discrepancy in 17 studies of unselected populations in Europe and the Americas is only 3.7% (interquar-tile range, 2% to 9.6%).

Two retrospective cohort studies of men with previous cryptor-chidism assessed paternity in 145 (Gilhooly et al, 1984) and 40 (Cendron et al, 1989) cases. Together, these studies identified successful paternity in 100 of 123 (81%) men with a history of unilateral and 19 of 54 (35%) of men with a history of bilateral cryptorchidism. Lee and colleagues published a series of well-designed case control studies of fertility in cryptorchidism (Lee et al, 1996, 1997, 2000; Coughlin et al, 1999; Lee and Cough-lin, 2001, 2002b; Bellis, 2005; Lee, 2005) Questionnaire, hormone, semen analysis, and paternity data were analyzed for a large cohort of men who underwent orchidopexy between 1955 and 1975 and a control group of similar age who were matched for timing of unrelated surgery. For all married or cohabitating men, 32 of 88 (36%) former bilateral, 322 of 609 (53%) former unilateral, and 413 of 708 (58%) controls had fathered children. Of those attempting paternity, 32 of 49 (65%) former bilateral, 322 of 359 (90%) former unilateral, and 413 of 443 (93%) controls were successful. There were no significant differences between the unilateral and control groups and no differences between groups in the frequency of attempted paternity or in other lifestyle factors that may adversely affect fertility. The fre-quency of successful paternity did not differ between men with previous unilateral cryptorchidism who had undergone orchiec-tomy and the control group. Relative risk for infertility was increased after hCG treatment (RR 4.7, P = .002) but not with higher testicular position or age at orchidopexy. Sperm density was less than or equal to 13 × 106/mL in all 8 patients with bilateral cryptorchidism that were studied; however, 3 of these men had fathered children (Lee and Coughlin, 2001). In contrast to previ-ous studies, 83% of men in the unilateral group had normal sperm density and sperm motility and morphology did not differ from control values. Although hormone levels alone did not correlate directly with fertility, abnormal levels of serum inhibin-B, FSH, and/or sperm density provided cumulative risk of decreased fertil-ity. However, the authors conclude that prediction of infertility is difficult in the absence of azoospermia or severe oligospermia. These investigators also found differences in basal and stimulated LH and in serum testosterone levels when comparing fertile and infertile or subfertile formerly cryptorchid men and suggest that global testicular dysfunction occurs in cryptorchid males. More-over, there is some evidence from these studies of a relationship between improved testosterone, inhibin-B, and FSH levels in males who underwent earlier orchidopexy (Coughlin et al, 1999; Lee and Coughlin, 2002a).

Limited evidence suggests that defective spermatogen-esis may exist in some adult patients with persistently retractile testis or with milder forms of acquired crypt-orchidism with or without apparent spontaneous descent of the testis at puberty. In small, retrospective outcome studies, Puri and Nixon (1977) reported 74% paternity and normal testicu-lar volume in a series of 43 adults with untreated retractile testes in childhood. Conversely, Nistal and Paniagua (1984) and Caroppo and colleagues identified 23 and 34 males, respectively, from infer-tility clinic data and identified poor semen parameters in the


microlithiasis in primarily white boys shows that the prevalence is 4.2% and increases with age (Goede et al, 2009). In about half of these cases, the degree of microlithiasis was limited, defined as less than five lesions per testis, and not considered clinically sig-nificant. Slaughenhoupt and associates (2009) reported a case and reviewed pediatric reports of TGCT or yolk sac tumor in boys with microlithiasis but without other risk factors; they recommend periodic examination and ultrasonography in all cases. In con-trast, biopsies are performed in adults with microlithiasis and one other risk factor for tumor, such as cryptorchidism, but if the biopsy is negative then no specific follow-up other than self-examination is recommended (van Casteren et al, 2009). Testicular self-examination, which requires education and counseling of the patient, remains a mainstay of testicular cancer screening. A description exists (http://www.cwpeds.com/pdfs/adolescents/TesticularExam.pdf), and it should be taught to all patients with a history of cryptorchidism after they reach puberty, preferably by the pediatric urologist or operating surgeon in addition to the primary care practitioner.

VARICOCELEA scrotal varicocele is an abnormal dilation and tortuosity of the internal spermatic veins within the pampiniform plexus of the spermatic cord. Like cryptorchidism, varicocele is a common finding in otherwise normal males, may contribute significantly to the risk of infertility in adulthood, and is associated with a natural history that is poorly understood. Although varicocele is clearly a risk for subfertility in certain individuals, its effect on paternity is less clear because about 85% of men with varicocele in population-based studies have fathered children (Pinto et al, 1994; Safarinejad, 2008). There are few well-designed prospective studies of adult or pediatric populations that clarify the risk factors for associated testicular dysfunction in males with vari-cocele. Moreover, recent data add further confusion to the debate regarding which varicoceles require treatment during adolescence.

Epidemiology and PathogenesisAlthough considered a congenital lesion, varicocele is rarely diag-nosed before school age, and the frequency and severity vary with age, method of diagnosis, and Tanner stage. Population data from large groups of children and adolescents suggest that the majority

Recently, in their exhaustive analysis of the literature Wood and Elder (2009) clarified the nature of increased TGCT risk in the previously cryptorchid and contralateral descended testis. Men with a history of cryptorchidism comprise about 10% of those presenting with TGCT. The relative risk of malignant trans-formation in an undescended testis is 2.5 to 8 overall and 2 to 3 in boys undergoing prepubertal orchidopexy, which is lower than historical estimates. This incidence correlates with the reported risk of CIS of 2% to 3% in previously cryptorchid men (Giwercman et al, 1989); a much lower risk (0% to 0.4%) was reported in children with nonsyndromic cryptorchi-dism (Cortes et al, 2001; Husmann, 2005). TGCT may occur in the contralateral descended testis of men with a history of unilateral cryptorchidism, but Wood and Elder (2009) conclude that the relative risk of only 1 to 2 indicates a level comparable to the general population that is not related to cryptorchidism per se. However, a recent meta-analysis shows that the relative risk of 6.3 (95% CI, 4.30 to 9.31) in the ipsilateral and 1.7 (95% CI, 1.01 to 2.98) in the contralateral testis is significant compared with con-trols (Akre et al, 2009). In another meta-analysis, Walsh and asso-ciates (2007) determined that the relative risk of testicular cancer was 5.8 (95% CI, 1.8 to 19.3) in men who underwent orchidopexy after age 10 to 11 as compared with those undergoing earlier cor-rection. However, recent population-based data are conflicting, showing twice the risk of malignancy in orchidopexy cases oper-ated at or after age 13 in one series (Pettersson et al, 2007) but no age-dependent differences in another (Myrup et al, 2007), possibly related to ascertainment bias in the latter series. Further studies are needed to clarify the relationship between age at orchidopexy and risk of testicular cancer. Review of tumor pathology in treated versus untreated cryptorchidism shows that seminoma is associ-ated with persistently cryptorchid testes (74%) and nonseminoma is present in the majority of scrotal testes (63%) (Wood and Elder, 2009).

Certain subgroups with undescended testis are at increased risk for TGCT, including those with chromosomal defects and other genital anomalies (Cortes et al, 2001; Husmann, 2005). Husmann (2005) recommends that biopsy be performed in these individuals and in boys older than 12 undergoing orchidopexy, although the age cutoff and usefulness of biopsy during pubertal orchidopexy have not been clearly defined. Orchiectomy should be considered the preferred treatment of cryptorchid testes from puberty to the age of 50 (Wood and Elder, 2009). Swerdlow and associates (1997) reported in a retrospective cohort study that testicular biopsy at orchidopexy was associated with a relative risk of 6.7 for future TGCT compared with orchidopexy without biopsy, but the indica-tions for biopsy in this series were not clearly known. A subse-quent report from a large Scandinavian cohort showed that universal biopsy did not appear to increase the risk for TGCT beyond what is expected for previously cryptorchid men (Moller et al, 1998).

Testicular microlithiasis, characterized by multiple spectral cal-cifications within the testicular parenchyma (Fig. 132–5), is more frequently present in men with ITGCNU and germ cell tumors but is also present in 5% to 10% of the normal population and in a similar proportion of previously cryptorchid men (Patel et al, 2005; van Casteren et al, 2009). Although concern exists that the risk for TGCT may be higher when cryptorchidism coexists with microlithiasis in individual patients, the appropriate follow-up strategy remains undefined. Even less well defined is the significance of microlithiasis in general, which is not clearly shown to be an independent risk factor for TGCT. A recent population-based analysis of the prevalence of

Figure 132–5. Testicular microlithiasis found incidentally in a 13-year-old boy with early puberty (Tanner stage II) and a clinical appendix testis torsion. The remainder of the study showed normal Doppler flow to testis, increased epididymal flow, and no visible appendage. The examination findings normalized within 1 week.

http://www.cwpeds.com/pdfs/adolescents/TesticularExam.pdf

http://www.cwpeds.com/pdfs/adolescents/TesticularExam.pdf


vasectomy or male kidney donors and especially high in brothers (Raman et al, 2005; Mokhtari et al, 2008). Studies using CDUS show that risk of varicocele progression during adolescence may be related to the prevalence of continuous or spontaneous as opposed to Valsalva-induced spermatic venous reflux (Pfeiffer et al, 2006; Cervellione et al, 2008; Zampieri and Cervellione, 2008). The underlying pathologic process is unknown but assumed to be related to the unique angle of the spermatic vein/renal con-fluence on the left side coupled with increased hydrostatic pres-sure and/or valvular incompetence (Zini and Boman, 2009). The “nutcracker phenomenon,” defined as compression of the left renal vein between the aorta and superior mesenteric artery, was identified in a subset of affected boys by venography and CDUS and may contribute to the pathogenesis of varicocele (Coolsaet, 1980; Kim et al, 2006). Increased height and relatively lower weight and body mass index (BMI), a classic tall, thin body habitus, is associated with varicocele in adolescents and adults in clinical as well as screening populations (Handel et al, 2006; May et al, 2006b; Nielsen et al, 2006; Kumanov et al, 2008; Tsao et al, 2009) and may contribute to risk via increased spermatic vein length and/or hydrostatic pressure. Alternatively, the diagnosis may be less common in obese individuals owing to increased scrotal wall fat that reduces diagnostic sensitivity. In a recent study not yet confirmed by other investigators, Sakamoto and Ogawa reported greater peak and antegrade flow and venous diameter in the pros-tatic venous plexus of men with bilateral varicoceles, who com-prised 33% of their series of 141 men with varicoceles, compared with controls and men with unilateral varicoceles (Sakamoto and Ogawa, 2008). These data are consistent with other studies show-ing increased risk of saphenofemoral junction incompetence (Karadeniz-Bilgili et al, 2003) and varicose veins (Kilic et al, 2007) in cases of varicocele, reflecting the possibility of a generalized venous abnormality.

Diagnosis and ClassificationAlthough screening programs exist in some communities, the majority of varicoceles in children and adolescents are identified incidentally by a primary care practitioner and less commonly due to patient complaints of discomfort or scrotal swelling. Associated pain is reported in 2% to 11% of cases (Zampieri et al, 2008a) and may be a more common finding in some geographic regions. In rare cases, a varicocele is diagnosed after rupture due to sports-related or other trauma.

The patient is examined in a warm room in the supine and standing positions. The scrotum is observed for visible swelling, and the spermatic cord is palpated at rest and during the Valsalva maneuver. The standard grading system used for varicoceles is grade 1, palpable only with Valsalva; grade 2, easily palpable but not visible, and grade 3, easily visible. A large varicocele should decompress in the supine position; failure to decompress, particu-larly on the right side, is an extremely rare finding but warrants evaluation for an abdominal mass (Roy et al, 1989). Grade 0 (sub-clinical) varicoceles are visualized by CDUS but are nonpalpable. As noted earlier, the use of CDUS to diagnose varicoceles increases the disease prevalence in any given population because subclinical varicoceles are identified. In adults, a subclinical right-sided vari-cocele was diagnosed about 10 times more often when thermog-raphy (measurement of scrotal temperature), CDUS, or venography was used as compared with physical examination only (Gat et al, 2004). However, significant controversy exists even in the infertile adult population regarding the need to diagnose and treat non-palpable varicoceles.

appear after the age of 10 and that the risk rises with progression through puberty, reaching a peak at Tanner stage 3 (Kumanov et al, 2008). The prevalence rate of clinically diagnosed varicoceles in this population is 8% to 16%, similar to that reported for the adult population, but ranges from 3% to 43% between studies (Niedzielski et al, 1997; Skoog et al, 1997; Akbay et al, 2000; Stavropoulos et al, 2002; Kumanov et al, 2008; Zampieri and Cervellione, 2008). Although almost all reported varicoceles were left sided in older studies, some recent series report a 7% to 10% bilateral incidence and color Doppler ultrasonography (CDUS)–based evaluation identified additional subclinical left or bilateral varicoceles in 7% to 17% of adolescent cases (Akbay et al, 2000; Pfeiffer et al, 2006; Cervellione et al, 2008). Bilateral repair of palpable (primarily grade 1) varicoceles was performed in one third of 10- to 24-year-old males in a recent series (Decastro et al, 2009), suggesting that a right-sided varico-cele may be more common in adolescents than previously recog-nized. In adults, bilaterality is reported in 15% to 50% of cases (Zini and Boman, 2009).

The cause for the appearance and, in some cases, pro-gressive severity of varicoceles in children and adoles-cents has not been clearly defined, but susceptibility is likely determined by genetic predisposition, body habitus, and/or intrinsic venous abnormalities. Genetic factors likely contribute to the risk, but not necessarily the sever-ity, of varicoceles. The risk of varicocele in first-degree relatives was four to eight times the risk in fertile men undergoing

Key Points: Cryptorchidism

● Cryptorchidism occurs in 1% to 4% of full-term males; post-natal spontaneous descent and reascent of testes are common.

● The causes of cryptorchidism are largely unknown, but birth weight, gestational age, genetic, and environmental risk factors likely contribute to disease risk.

● The diagnosis of cryptorchidism may be “acquired,” that is, made in cases of apparent full descent at birth or after spon-taneous descent of a cryptorchid testis and may be more common in boys with retractile testes. Yearly testicular examinations are recommended.

● About 80% of undescended testes are palpable, and 60% to 70% are unilateral.

● Many boys with nonsyndromic cryptorchidism have epi-didymal anomalies and a patent processus vaginalis, and some have reduced LH and/or testosterone levels during the postnatal surge.

● Orchidopexy is recommended for testes that remain unde-scended after 6 months of age; hormone therapy is not recommended.

● Laparoscopy is the procedure of choice, and imaging studies have limited value in the diagnosis and treatment of intra-abdominal cryptorchidism.

● Sperm counts are reduced in at least 25% of formerly uni-lateral and the majority of formerly bilateral cryptorchid men, but paternity rates in the unilateral group are similar to those of control men.

● Adult dark (Ad) spermatogonia counts may predict fertility potential in males with cryptorchidism.

● The relative risk of malignancy in cryptorchid testes is 2 to 8 and may be 2 to 3 after prepubertal orchidopexy.


will likely yield greater differential volumes when ultrasonography is used. However, based on studies of the 6- to 13-mL canine testis, ultrasound measurements and the Lambert formula provide the most accurate and precise testicular volume estimates (Paltiel et al, 2002).

Associated Pathologic ProcessesThere is abundant evidence that a varicocele may alter testicular growth, spermatogenesis, and fertility potential. The etiology of testicular injury is presumed to be related to increased scrotal temperature, but the pathogenesis remains poorly understood. Moreover, the ability to conceive exists in the majority of men with varicoceles. The appropriate treatment of children and adolescents with varicoceles should be selective, based on the presence of risk factor(s) predictive of long-term subfertility.

Testicular HypotrophyThe association of varicocele with a relative decrease in volume of the left testis has been known for many years (Lipshultz and Corriere, 1977). In his population-based survey of adolescents and young adults, Steeno (1976) observed but did not quantify an adverse effect of grade 2 and 3 varicoceles on testicular volume and/or consistency. Subsequently, others (Lyon et al, 1982; Kass and Belman, 1987) showed that relative left testicular volume loss is common in adolescents with varicocele, may improve or resolve after varicocele correction, and therefore may reflect sig-nificant testicular injury. Significant left hypotrophy is variously defined as a 10%, 15%, 20%, 2- or 3-mL relative difference in testicular size and reportedly present in 10% to 77% of cases (Lyon et al, 1982; Okuyama et al, 1988; Akbay et al, 2000; Thomas and Elder, 2002; Diamond et al, 2004b; Kolon et al, 2008; Preston et al, 2008). Variability of this finding is likely related to the method of measurement (visual estimation, orchidometer, or ultrasound with varying computational formulas used), referral patterns, and the formula used to determine percent difference between testes. Moreover, population-based data show that a rapid increase in testicular size may occur as early as 10 years of age and persist until age 19, depending on the popula-tion studied and the Tanner stage of pubertal development (Tables 132–2 and 132–3) (Schonfeld, 1943; Rundle and Sylvester, 1962; Zachmann et al, 1974; Daniel et al, 1982; Matsuo et al, 2000) and can vary widely between individuals particularly between 13 and 14 years of age (Marshall and Tanner, 1970). Therefore lon-gitudinal measurements over several years may define testicular hypotrophy more accurately than single measurements, particu-larly in early puberty. Most often, size differential is calculated as follows:

Percent difference

right testicular volume

left testi

=× −100 (

ccular volume right testicular volume)/ ,

although Kolon and associates (2008) use the formula:

100 × −( /right testicular volume total testicular volume

left ttesticular volume total testicular volume/ ).

Varicocele grade is positively associated with risk of left testicular hypotrophy in some studies (Thomas and Elder, 2002; Zampieri et al, 2008b) but not others (Alukal et al, 2005; Kolon et al, 2008).

The appropriate criteria for varicocele diagnosis using CDUS are controversial in adults, and experience with this use is limited in the pediatric and adolescent population. As reviewed by Lee and associates (2008), standards used for spermatic vein diameter (typi-cally > 3 mm) and presence of retrograde flow vary in adult studies, although diagnostic accuracy may be increased using a combination of criteria. In a study of 625 boys with varicocele and 50 normal controls, Niedzielski and colleagues (1997) mea-sured spermatic vein diameter in the standing position and venous reflux with Valsalva maneuvers. Using 2 mm as the upper limit of normal spermatic vein diameter based on findings in normal boys, these researchers obtained normal measurements in 95%, 70%, and 4% of boys with grades 1, 2, and 3 varicoceles, respec-tively. Similarly, spermatic venous diameter as measured in the supine position was a poor criterion for clinical varicocele and did not predict risk of testicular volume loss in a smaller series of boys with varicocele (Kozakowski et al, 2009). In studies of sper-matic venous blood flow, reflux was identified in two thirds of boys with grade 2 or 3 varicoceles and flow velocity measured in the standing position correlated with grade of varicocele and sperm motility (Niedzielski et al, 1997). Kozakowski and cowork-ers (2009) measured supine peak retrograde spermatic vein flow with Valsalva maneuvers and noted that high flow rates (>38 cm/sec) were strongly associated with testicular volume asymmetry. The significance of these data is unclear, because the usefulness of spermatic vein flow measurement in adolescents will require standardization and prospective correlation with functional outcome.

Testicular size and consistency should be documented at the initial examination and at intervals during follow-up. The affected testis may be unusually soft, but the prevalence and relevance of this finding is not well documented. Although analysis of bilateral testicular volume is important, there is no consensus regarding the appropriate method of analysis. Options include calipers to measure testicular length, width, and depth or one of two com-monly used orchidometers. The Prader orchidometer is a chain of 12 solid wooden ellipsoids with volumes of 1 to 6, 8, 10, 12, 15, 20, and 25 mL that are visually compared with the size of each testis. The Takihara orchidometer comprises 15 elliptical rings with inner dimensions corresponding to ellipsoid volumes of 1 to 6, 8, 10, 12, 14, 16, 19, 22, 26, and 30 mL that are placed over the widest circumference of the testis. Alternatively, ultrasonic place-ment of electronic calipers in three dimensions can be used with volume calculated by one of several formulas, the most common being the Lambert formula, 0.71(length × width × depth) or the volume of a rotational ellipsoid, 0.52(length × width × depth) or 0.52(length × depth2). Costabile and colleagues (1992) performed blinded measurements of models of known volume using ultraso-nography and the rotational ellipsoid formula and showed an overall standard deviation of 1.6 mL but less variation for volumes less than 10 mL. Studies assessing the relative accuracy of mea-surements obtained using ultrasonography and orchidometers in children and adolescents suggest that while all techniques are reliable, ultrasonography is more sensitive in determining differ-ences in size between the left and right testis (Costabile et al, 1992; Chipkevitch et al, 1996; Diamond et al, 2000). Because orchidom-eter volume estimates are routinely greater than those determined using ultrasound and the rotational ellipsoid formula, calculation of differential volume using the following formula

( [ ]

[

Right unaffected testicular volume

left affected] test

−iicular volume right testicular volume)/


not presently available, ultrasound-derived size measurements for each testis based on population-specific norms and comparison with outcome would provide further insight into this question.

“Catch-up” growth, defined as normalization of left relative to right testicular size, occurs in 32% to 83% of patients after varico-cele repair (Cayan et al, 2002; Greenfield et al, 2002; Yaman et al, 2006; Castagnetti et al, 2008; Feber and Kass, 2008; Decastro et al, 2009; Poon et al, 2009; Zampieri et al, 2009) and in 55% to 70% of boys on average in various series (Barroso et al, 2009). A conclu-sion that postoperative testicular catch-up growth is less likely in boys older than 14 (Cayan et al, 2002) was not supported by another study addressing this issue (Decastro et al, 2009). Most clinicians believe that postoperative resolution of left testicular hypotrophy is evidence that varicocele repair improves testicular function in adolescents. However, a clear understanding of the relationship between varicocele repair and restoration of testicular growth is complicated by observations that testicular size differ-ential may improve spontaneously in untreated patients, varico-cele may affect growth of both testes, testicular edema or venous stasis may hypothetically contribute to testicular enlargement, catch-up growth may occur despite surgical failure, and improve-ment in sperm counts does not necessarily correlate with catch-up growth. In an early observational study, Paduch and Niedzielski (1997) observed some improvement in mean testicular volume differential in boys followed expectantly without surgery. Kolon and coworkers (2008) reviewed serial ultrasound studies performed at least 6 months apart (≥3) in 71 boys observed without interven-tion for an average of 3.5 years and noted asynchronous testicular growth in many. Using a 15% volume differential as a normal cutoff, these authors observed hypotrophy in 54% of boys initially and only 15% at final follow-up, suggesting that the majority of potential surgical candidates may normalize with time without treatment. Similarly, Preston and colleagues (2008) reported nor-malization of hypotrophy in 50% of 33 boys followed a median of 2.12 years; neither of these studies showed deterioration to greater than 20% hypotrophy during observation. In contrast, other investigators rarely noted spontaneous catch-up growth but reported worsening or development of significant hypotrophy in 10% to 26% of boys over time (Thomas and Elder, 2002; Koza-kowski et al, 2009; Zampieri and Cervellione, 2008), whereas others reported no statistical difference in either direction in lon-gitudinal studies (Diamond et al, 2004b). The fact that intra-individual testicular volume differential may change significantly over time supports the conclusion (reached by Kolon et al, 2008) that normal pubertal testicular devel-opment may be asynchronous. Alternatively, testicular size may appear variable over time because of inherent error in measurement techniques. These same factors may bias reported postoperative results showing testicular volume improvement that do not include an untreated comparison group.

Kocvara and colleagues (2003) reported significant testicular growth as early as 6 weeks after surgery, enhanced catch-up growth with lymphatic and arterial ligation, and intratubular edema in several biopsies obtained at hydrocele repair several years after non–lymphatic-sparing varicocelectomy with or without artery sparing. Their hypothesis that lymphatic ligation may contribute to increased testicular volume is not consistent with data from other centers showing no difference in rates of catch-up growth based on lymphatic (Poon et al, 2009) and/or arterial (Barroso et al, 2009) preservation. Moreover, Laven and associates (1992) noted that varicocele repair increased the volume of small but not normal-sized testes in their series. Postoperative left testicular hypertrophy (>10% size differential relative to the right testis) is

Kass and colleagues (2001) compared 434 varicocele cases and 70 controls of similar age (mean 14 years) and noted that right testicular size was also significantly reduced compared with control values in Tanner stage 4 to 5 males with grade 3 varicocele. Okuyama and coworkers (1988) reported testicular hypotrophy (size < 2 SD below the mean for Japanese boys) on the side con-tralateral to a grade 2 or 3 varicocele in 22% of their patients, and their data suggested lower sperm density in patients with bilater-ally small testes. Mean right testicular volume increased signifi-cantly after left varicocele repair but not in untreated control groups in several other studies (Laven et al, 1992; Yamamoto et al, 1995; Paduch and Niedzielski, 1997). Paduch and Niedzielski (1996) reported a correlation between total testicular volume and sperm concentration in adolescents but did not observe a signifi-cant decrease in right testicular size between varicocele patients and controls. Consequently, the significance of global testicular size in boys with left varicocele remains poorly defined. Although

Table 132–2. Tanner Stages

Pubic Hair

1 No pubic hair2 Sparse growth of long, slightly pigmented downy hair

primarily at base of penis3 Darker, coarser, and more curled hair spreading sparsely

over the pubic region4 Adult-type hair covering an area smaller than in most adults5 Adult-type hair in typical adult male distribution extending

up linea alba and to medial surface of thighs(6) Further spread of hair after puberty (not used routinely)

Genitalia

1 Testes, penis, and scrotum same proportional size as in early childhood

2 Enlargement of scrotum and testes with change in texture and reddening of scrotal skin

3 Growth of the penis, first in length and then breadth; further growth of scrotum and testes

4 Further growth of penis in length and breath; development of glans and testes; scrotum further enlarged and darkened

5 Genitalia adult size and shape without further enlargement

Table 132–3. Testicular Volumes Based on Tanner Stage

TANNER STAGE*

Daniel et al, 1982†Zachmann et al, 1974‡

Left Testis (cm3) Right Testis (cm3) Total (mL)

Mean SD Mean SD Mean SD

1 4.8 2.8 5.2 3.9 6.0 2.62 6.4 3.2 7.1 3.9 6.8 3.63 14.6 6.5 14.8 6.1 9.3 3.84 19.8 6.2 20.4 6.8 12.6 4.25 28.3 8.5 30.2 9.6 16.3 4.66 18.9 4.0

*Pubic hair staging (Zachmann et al, 1974) or mean of genital and pubic hair staging (Daniel et al, 1982).

†Data based on length and width measurements (0.52 × L × W2) of 348 U.S. males age 12 to 19 years.

‡Data based on orchidometer measurements of 2139 Swiss males age 12.5 to 20 years.


abnormal tubular maturation and Leydig cell number but were unable to correlate these data with ultimate sperm quality in adulthood.

Hormonal FunctionKass and colleagues (1993a) reported an exaggerated LH and FSH response to gonadotropin-releasing hormone (GnRH) stimulation in about 30% of boys with varicocele, although they were unable to show a correlation with testicular hypotrophy. Similar data were reported in a smaller study that also included inhibin-B measure-ments (Carrillo et al, 1999), which have also not shown consistent correlation with testicular size or semen parameters in adolescents or adults with varicocele (Turkyilmaz et al, 2006; Romeo et al, 2007; Basar et al, 2010). Aragona and associates (1994) identified severe germ cell abnormalities in 3 of 15 adolescents with grade 2 to 3 left varicocele and 2 of these boys had exaggerated LH and FSH response to GnRH, but 2 others with increased LH response had normal histology, and none of their patients had more than 12% left testicular hypotrophy. Baseline LH and FSH levels are not consistently different in the presence or absence of varicocele during adolescence in most studies (Laven et al, 1992; Yamamoto et al, 1995; Cayan et al, 2005; Ku et al, 2005). Guarino and coworkers (2003) observed increased LH, FSH, and simulated FSH levels in 20 varicocele patients with abnormal semen parameters (age 16 to 19, Tanner stage 5) compared with 56 with normal semen, but 6 of the former group had bilateral varicoceles, a history of inguinal surgery, or cryptorchidism. Basal and stimu-lated gonadotropin levels were not consistently different in vari-cocele patients when compared with controls and did not improve after surgery in another series (Fideleff et al, 2000). GnRH stimula-tion testing is not presently used routinely as an indication for varicocele surgery in adolescents because of lack of correlation with testicular size differential; however, further studies are war-ranted because hypotrophy itself does not always correlate with outcome or with histologic changes in the testis.

Semen QualityDespite many variables associated with collection and inter-pretation of semen analysis samples, semen quality is considered the most useful indicator of fertility potential. Because of wide variation in sexual maturation, age alone is not a good criterion to establish reliability of semen analysis results. Janczewski and Bablok (1985a to 1985d) compared bone age, testicular size, Tanner stage, hormone levels, and timing of first ejaculation with attainment of normospermia in a series of 134 Polish boys aged 12 to 19 years old. In these studies the first ejaculation occurred beginning at a bone age of 13 years, 16 months or earlier after the beginning of puberty, and the majority of boys met criteria for normospermia by a bone age of 17. Tanner stage 5 was associated with asthenozoospermia and occasional oligo-zoospermia in addition to normospermia. Mean testicular size based on caliper measurements increased with progression in semen quality but showed a large standard deviation in boys achieving normospermia, and a significant drop in LH and FSH levels occurred with attainment of normospermia. Because pro-gressive improvement in sperm quality may parallel continued growth of the testis through the teenage years, semen analyses may not reliably predict testicular function in boys with varicocele before completion of testicular growth.

A number of studies are now available that report semen analy-sis data in males diagnosed with varicocele, usually grade 2 or 3, in adolescence (Table 132–4). In the majority of these studies, at

reported in several studies and attributed to non–lymphatic- sparing procedures or to a rebound effect on spermatogenesis in the affected testis (Gershbein et al, 1999; Cayan et al, 2002; Kocvara et al, 2005).

To date, no studies clearly define the natural history and rela-tionship, if any, between testicular hypotrophy in adolescence and that seen in adulthood. In a retrospective review, Sayfan and col-leagues (1997) reported long-term follow-up data in 32 men who underwent varicocele repair at 11 to 15 years of age, comprising 27% of a cohort treated between 1972 and 1982. In comparing this group with normal controls and untreated men with varico-celes, they noted similar semen quality and no testicular volume differential in treated and control groups, and significantly lower sperm counts and smaller left testes in the untreated group, but did not clarify how this latter population was identified. Despite these data, it is important to note in the general adult population with varicoceles that testicular hypotrophy is not a clear risk factor for infertility. Mean testicular volume differential in unselected fertile men with varicoceles (3.1 ± 0.3 mL) was not significantly different from that found in infertile men with varicoceles (2.5 ± 0.6 mL), and 82% of all men with varicoceles and 68% of those with grade 3 (not statistically different from the entire group) had evidence for normal fertility (Pinto et al, 1994). Other studies support the finding that left testicular volume is smaller in both fertile and infertile men with varicoceles but that bilateral hypot-rophy is more common in the infertile group (Pasqualotto et al, 2005; Shiraishi et al, 2009). Shiraishi and associates (2009) suggest that additional cofactors contribute to the risk of infertility in men with varicoceles. In 611 patients with varicoceles (45% with grade 2 or 3) presenting for infertility evaluation, Sigman and Jarow (1997) reported testicular size discrepancy of at least 3 mL in 50%, with higher grade and lower total motile sperm counts (corrected for grade) in those with this finding. In contrast, in another study of 245 men presenting for infertility with varicoceles (90% with grade 2 or 3), bilateral but not unilateral hypotrophy was a signifi-cant predictor of abnormal total motile sperm count (Wu et al, 2008).

Significant discrepancy between left and right testicular size is considered the most reliable clinical risk factor available and remains the primary indication for varicocele correction. Unfor-tunately, the available data do not provide a clear picture of the effect of varicocele or its correction on testicular growth and func-tion in individual patients. The presence of hypotrophy is not invariably associated with reduced fertility potential, but other predictors such as varicocele grade, global testicular growth, and hormonal studies have not been critically evaluated in adoles-cents. Prospective, randomized studies are needed to clearly establish whether unilateral and/or bilateral testicular hypotrophy or catch-up growth accurately predict fertility potential in adolescent varicocele.

Testicular HistologyAlthough extensively studied in adults (reviewed by Hienz et al, 1980), histologic data from testicular biopsies of adolescents with varicocele have been limited and inconsistent. These biopsy find-ings vary from normal histology by light and electron microscopy in all (Fideleff et al, 2000) or most normal men with severe hypo-spermatogenesis in a minority of cases (Kass et al, 1987; Aragona et al, 1994) to degenerative tubular changes, altered Leydig cell number, and/or proliferative lesions of the vasculature in the majority of cases (Hienz et al, 1980). In a small retrospective series of men who underwent testicular biopsy at the time of adolescent varicocele repair, Hadziselimovic and associates (1995) observed


Tabl

e 13

2–4.

Se

men

An

alys

is R

esu

lts

in A

do

lesc

ent

Var

ico

cele

STU

DY

GR

OU

PSA

GE

SEM

EN A

NA

LYSI

SG

RA

DE

FIN

DIN

GS

Ran

dom

ized

Cas

es v

s. C

ontr

ols

Lave

n e

t al

, 199

227

tre

ated

17-2

02

2-3

Init

ial S

C 4

3-52

± 3

2-44

× 1

06 /mL

(NS

bet

wee

n g

rou

ps)

; tre

ated

gro

up

in

crea

sed

to

69 ×

106 /M

l (P <

.01)

at

1 ye

ar; n

o c

on

sist

ent

corr

elat

ion

of

sem

en q

ual

ity

wit

h c

atch

-up

gro

wth

26 u

ntr

eate

d16

co

ntr

ols

Yam

amo

to e

t al

, 199

529

tre

ated

15-1

91

1-2

Init

ial S

C 4

9-51

± 1

6-32

× 1

06 /mL

(NS

bet

wee

n g

rou

ps)

; tre

ated

gro

up

in

crea

sed

to

74 ×

106 /m

L (P

< .0

02)

at 1

yea

r22

un

trea

ted

17-2

118

co

ntr

ols

14-2

0

Unt

reat

ed C

ases

vs.

Con

trol

s

Haa

ns

et a

l, 19

9167

un

trea

ted

17-2

12

2 (1

5)SC

< 2

0 ×

106 /m

L in

19%

co

ntr

ols

, 20%

gra

de

2 an

d 1

3% g

rad

e 3

(NS)

. C

orr

elat

ion

(r =

.26,

P =

.03)

bet

wee

n le

ft t

esti

cula

r vo

lum

e an

d t

ota

l sp

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co

un

t b

ut

no

t SC

21 c

on

tro

ls3

(52)

Pad

uch

an

d

Nie

dzi

elsk

i, 19

9636

un

trea

ted

17-1

92

2-3

SC 5

3 ±

31 ×

106 /m

L in

cas

es a

nd

56 ±

36 ×

106 /m

L in

co

ntr

ols

(N

S); s

ign

ifica

nt

dif

fere

nce

s in

mo

tilit

y an

d v

ital

ity

bet

wee

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rou

ps;

sp

erm

co

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ntr

atio

n

corr

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ed w

ith

to

tal t

esti

cula

r vo

lum

e38

co

ntr

ols

Ced

enh

o e

t al

, 200

220

un

trea

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Mea

n 1

61

2-3

SC 5

7 ±

55 ×

106 /m

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cas

es a

nd

73 ±

54 ×

106 /m

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co

ntr

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(N

S), i

mp

aire

d

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on

a p

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ind

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cap

acit

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ases

)20

co

ntr

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Ber

tolla

et

al, 2

006

20 u

ntr

eate

d15

-17

12-

3SC

78 ±

17 ×

106 /m

L in

cas

es a

nd

86 ±

25 ×

106 /m

L in

co

ntr

ols

(N

S), i

ncr

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d

sper

m D

NA

fra

gmen

tati

on

(ca

ses)

20 c

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tro

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ilat

Mo

ri e

t al

, 200

867

un

trea

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14-1

81

2 (4

9)SC

50 ±

52 ×

106 /m

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gra

de

2, 3

7 ±

41 ×

106 /m

L in

gra

de

3, a

nd

88 ±

76 ×

106 /

mL

in c

on

tro

ls +

gra

de

1 (P

= .0

003)

160

con

tro

ls +

gr

ade

1T4

-53

(18)

Trea

ted

vs.

Unt

reat

ed C

ases

Oku

yam

a et

al,

1988

13 t

reat

ed18

≥32-

3N

orm

al S

A*

in 6

9% t

reat

ed a

nd

20%

un

trea

ted

cas

es (

P <

.05)

10 u

ntr

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dZ

amp

ieri

an

d

Cer

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on

e, 2

008

92 t

reat

ed18

22-

3W

HO

cri

teri

a† met

in 6

4% t

reat

ed (

all w

ith

hyp

otr

op

hy)

an

d 8

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ntr

eate

d

(no

ne

wit

h h

ypo

tro

ph

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NS)

; no

co

rrel

atio

n o

f SA

wit

h v

aric

oce

le g

rad

e o

r ca

tch

-up

gro

wth

127

un

trea

ted

Preo

pera

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vs.

Pos

tope

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ve

Cay

an e

t al

, 200

533

pre

op

erat

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and

p

ost

op

erat

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Mea

n 1

6.4

pre

op

erat

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12-

3 (4

8%

bila

tera

l)SC

22 ±

3.6

(SE)

× 1

06 /mL

bef

ore

an

d 4

0 ±

5.7 ×

106 /m

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28 ±

13 m

on

ths

(mea

n ±

SD

) af

ter

arte

ry/ly

mp

hat

ic s

par

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rep

air

(P =

.007

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Ku

et

al, 2

005

35 p

reo

per

ativ

e an

d

po

sto

per

ativ

e

15-2

02

Mo

stSC

32 ±

3 (S

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106 /m

L b

efo

re a

nd

41 ±

3 (S

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106 /m

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6 m

on

ths

afte

r ar

tery

/lym

ph

atic

sp

arin

g re

pai

r; %

mo

tile

sp

erm

incr

ease

d (

P <

.001

); m

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su

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ies

per

form

ed f

or

pai

n2-

3

Unt

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Gu

arin

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, 200

368

un

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16-1

9 T5

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wit

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bn

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(SC

× %

mo

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× %

ova

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57 u

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T51-

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:<1

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ypo

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ph

y (n

= 2

7), 6

4 (3

2-13

4)10

-20%

hyp

otr

op

hy

(n =

18)

, 32

(13-

94)

>20%

hyp

otr

op

hy

(n =

12)

, 10

(3-8

2)P =

.02 >

20%

vs.

< 1

0%; n

o c

orr

elat

ion

wit

h g

rad

e

2-3

*No

rmal

SA

defi

ned

as ≥3

0 ×

106 s

per

m/m

L, ≥

60%

mo

tilit

y, a

nd

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% n

orm

al m

orp

ho

logy

.†W

orl

d H

ealt

h O

rgan

izat

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(W

HO

) cr

iter

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106 s

per

m/m

L, ≥

50%

mo

tilit

y, a

nd

≥30

% n

orm

al m

orp

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logy

.N

S, n

ot

sign

ifica

nt;

SA, s

emen

an

alys

is; S

C, s

per

m c

on

cen

trat

ion

, mea

n ±

SD

un

less

no

ted

; T, T

ann

er s

tage

; TM

SC, t

ota

l mo

tile

sp

erm

co

un

t (v

olu

me ×

con

cen

trat

ion

× %

mo

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sp

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), ex

pre

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as

med

ian

(25

th t

o

75th

per

cen

tile

s).


least two semen samples were obtained using techniques meeting World Health Organization criteria in older teenagers, although Tanner stage 5 was not always specified. In two randomized studies comparing treated and untreated cases with controls, no differ-ences were found in semen quality at initial or follow-up analysis between groups, except for a significant postoperative increase noted in the treated group in both studies that exceeded sperm concentrations seen in controls (Laven et al, 1992; Yamamoto et al, 1995). The cause for improvement in semen quality above control levels was not clear to these investigators, but Laven and coworkers (1992) hypothesized a rebound in spermatogenesis. Significant increases in sperm concentration were also reported in uncontrolled studies, but these may be biased by variations in semen quality that occur with time in late adolescence. The major-ity of series comparing untreated cases with controls of similar age found no significant differences in semen between groups or consistent differences between nonrandomized treated versus untreated cases. Correlations between left or total testicular volume and semen parameters were noted by some investigators (Haans et al, 1991; Paduch and Niedzielski, 1996; Diamond et al, 2007) but not others (Guarino et al, 2003). Investigators were unable to correlate postoperative increases in left testicular volume or varicocele grade with semen analysis data in controlled (Laven et al, 1992) and uncontrolled (Cayan et al, 2002; Diamond et al, 2007; Zampieri and Cervellione, 2008) studies. Although there are insufficient data from randomized prospective studies, the available data suggest trends toward poorer sperm quality that may be limited to a subset of affected males with varicocele, but that grade and postoperative testicular catch-up growth do not reliably predict ulti-mate semen quality.

Intratesticular VaricoceleIn less than 2% of patients, a large varicocele may be associated with an intratesticular component that is diagnosed by ultrasound and otherwise unsuspected (Diamond et al, 2004a). Although it may be confused with lesions of the testis or rete testis, the diag-nosis is easily made by demonstration of venous flow in anechoic structures greater than 2 mm in diameter near the mediastinum testis that is enhanced by the Valsalva maneuver. Approximately one third are reported to be bilateral. Diamond and associates (2004a) suggest that these lesions may reflect increased risk to the testis and that surgery is therefore indicated.

TreatmentIn the past, varicocele was considered a progressive lesion because of its higher prevalence in men with secondary as opposed to primary infertility (Gorelick and Goldstein, 1993). However, in a more recent study the distribution of varicoceles by grade and the prevalence of unilateral and bilateral testicular hypotrophy were similar in both groups, although sperm counts were higher, sug-gesting a female factor, in secondarily infertile men (Walsh et al, 2009). Moreover, an 8-year longitudinal study of men with vari-cocele and normal sperm counts did not show worsening of semen quality over time (Lund and Larsen, 1998). These and other data do not support the belief that the effect of varicocele on testicular function is progressive or that unilateral testicular hypotrophy is necessarily indicative of infertility in men with varicocele (Jarow, 2001). Therefore observation remains the approach of choice for the majority of adolescents with varicocele. Despite pitfalls associated with the use of significant testicular hypotro-phy as the primary criterion for surgical intervention

and evidence that testicular size discrepancy may be variable during adolescence, the main indications for surgical intervention remain significant left (≥20%) or bilateral testicular hypotrophy, pain or abnormal semen analysis, the latter most reliable in boys of Tanner stage 5 and/or at least 18 years of age. Although not studied in detail, bilateral hypotrophy may be more ominous and an indica-tion for intervention but must be determined based on nomo-grams specific for the population, the patient’s Tanner stage, and the measurement technique being used. Pain is a rare indication for surgery, reported in only 2% to 10% of patients in most series and relieved by the procedure in 68% to 88% of patients (Zampieri et al, 2008a).

Surgical Repair of VaricoceleAs in adults, several techniques are used for repair of adolescent varicocele, including inguinal/subinguinal, laparoscopic/retroperitoneal, or venographic approaches. The most commonly used techniques are the microscopic subinguinal approach and the suprainguinal open or laparoscopic approach with either mass ligation of the cord above the vas (Palomo) or with lymphatic and/or artery-sparing techniques. The choice of procedure is depen-dent on surgeon preference, experience, and complication rates that vary based on technique and length of follow-up (Table 132–5: Poddoubnyi et al, 2000; Misseri et al, 2001; Greenfield et al, 2002; Esposito et al, 2004; Cayan et al, 2005; Kocvara et al, 2005; Schiff et al, 2005; Yaman et al, 2006; Castagnetti et al, 2008; Feber and Kass, 2008; Glassberg et al, 2008; Barroso et al, 2009; Diamond et al, 2009; Tong et al, 2009 and references therein). There are no existing long-term outcome data available to support the use of any particular approach. Differences between subingui-nal and suprainguinal approaches are primarily based on type and frequency of complications. In some series, the length of postop-erative follow-up may be inadequate to identify potential recur-rences, which as opposed to cases of persistence are first identified 6 months or more postoperatively (Glassberg et al, 2008). The latency period for appearance of a hydrocele may vary from a mean or median of a few months to almost 2 years postopera-tively, and some are not diagnosed for several years or longer (Misseri et al, 2001; Esposito et al, 2004; Feber and Kass, 2008). Although these may resolve spontaneously, up to one half may require intervention. Esposito and associates (2004) most com-monly treated postoperative hydrocele with scrotal aspiration, which was required a median of three times under anesthesia

Table 132–5. Results of Adolescent Varicocele Repair

PROCEDURERECURRENCE/PERSISTENCE HYDROCELE

TESTICULAR ATROPHY

Open suprainguinal (Palomo)

2%-4% 0%-30% (10%)*

Laparoscopic Nonlymphatic/

artery sparing0%-9% 11%-32%

(7%)* Artery and/or

lymphatic sparing1%-7% 0%-4%

Microscopic subinguinal

0%-10% 0%-6% Rare

Nonmicroscopic inguinal

7%-33% 8%-14%

Sclerotherapy 6%-35% Occasional Rare

*Number in parentheses refers to meta-analysis of Barroso et al, 2009.


peritoneum is identified and mobilized medially. The entire bundle of spermatic vessels above the vas is mobilized, isolated, and clipped or suture-ligated. Open or laparoscopic Palomo tech-niques are performed with and without transection of the vessels, but no evidence supports a preference for either approach. A microscopic lymphatic-sparing procedure may be performed through a retroperitoneal incision, with initial data in a small series showing no hydrocele or recurrence after short-term follow-up (Wong et al, 2009).

Laparoscopic varicocele repair is performed after standard place-ment of an umbilical trocar, which is usually performed in chil-dren using an open (Hassan) technique. The patient is placed in slight Trendelenburg position, and the bladder is emptied. After intraperitoneal insufflation with CO2, the spermatic cord is visual-ized and two additional port sites are placed under direct vision in the left midclavicular line just inferior to the umbilicus and in the lower midline or right lower quadrant for a left-sided varico-cele, triangulating with the umbilical port and the internal ring. Alternatively, some surgeons use ports in both lower quadrants. A peritoneal incision is made several centimeters or more superior to the internal ring and lateral to the spermatic vessels, and the vascular bundle and surrounding tissue are mobilized away from the peritoneum. For spermatic artery preservation, approaches similar to those used for subinguinal procedures can be used, including a laparoscopic Doppler probe and papaverine in addi-tion to the magnification provided by the laparoscope. Kocvara and colleagues (2005) recommend initially grasping the largest lateral vein to facilitate mobilizing the entire bundle. They noted that 1 to 3 lymphatics, which appear as clear tubular structures, accompany the artery and smaller veins and that in typical lymphatic-sparing procedures 5 to 12 can be identified and pre-served. The injection of vital dyes into the paratesticular tissues for visualization of the majority of lymphatics along the spermatic vessels has been reported but is not universally used because of potential technical challenges and risks associated with inadver-tent intratesticular injection (Schwentner et al, 2006; Makari et al, 2007). Options for vascular ligation include permanent (usually silk) sutures tied extracorporeally, locking metal clips to avoid slippage, or transection using the harmonic scalpel or vessel- sealing devices. To avoid recurrence, vein(s) accompanying the artery should be identified and ligated. In a variation of the usual approach, Cimador and colleagues (2008) used CDUS to search for dilated, refluxing deferential veins in the iliac fossa, which if present were ligated at the time of a laparoscopic Palomo proce-dure. The necessity of this approach in preventing persistent or recurrent varicoceles has not been shown, and a theoretical concern for vasal artery injury with concomitant spermatic artery ligation exists. Injury to the genitofemoral nerve has been reported in a limited number of adolescent and adult series of laparoscopic varicocelectomy, comprising a total of 3% of cases, and may be more commonly associated with use of cauterizing instrumenta-tion (Muensterer, 2008). This complication presents as postopera-tive paresthesias in the distribution of the nerve along the proximal anterior thigh that slowly resolves over weeks or months.

Sclerotherapy/EmbolotherapyAntegrade or retrograde injection of sclerosant or embolizing material has been used for many years to treat adults with vari-cocele, but published experience in children and adolescents is limited. In general, both retrograde (Reyes et al, 1994; Mazzoni et al, 1999; Alqahtani et al, 2002; Sivanathan and Abernethy, 2003; May et al, 2006a; Beutner et al, 2007; Granata et al, 2008; Reiner et al, 2008) and antegrade procedures are less successful

before resolution. Most surgeons proceed with formal scrotal hydrocele repair only in cases of large or symptomatic hydrocele, with repair ranging from 5% to 50% of affected patients in several recent series (Misseri et al, 2001; Esposito et al, 2004; Feber and Kass, 2008; Diamond et al, 2009).

Subinguinal/Inguinal Microsurgical VaricocelectomyThe subinguinal microscopic approach provides the advantages of facilitated artery- and lymphatic-sparing, high rate of success, and low risk of hydrocele but may be time consuming and requires microscopic surgical skills. Some advocate this approach to opti-mize artery sparing, based on the assumption that it is more likely to optimize testicular function (Goldstein, 1995). The procedure used in children is similar to that used in adults as originally pub-lished (Goldstein et al, 1992; Schiff et al, 2005). A 2.5- to 3-cm incision is made over or just above the external inguinal ring, and the spermatic cord is isolated with or without opening the external oblique fascia. In the procedure described by Goldstein and col-leagues (1992) the testis is delivered and all external spermatic and gubernacular veins are ligated, although not all surgeons deliver the testis. After incision of the internal spermatic fascia, the cord is examined using 10× to 25× magnification. Lower degrees of mag-nification (e.g., loupes) can be used but probably provide inferior results (Greenfield et al, 2002; Cayan et al, 2005; Diamond et al, 2009). External, internal, and vasal veins greater than 2.5 mm in diameter are ligated, and the spermatic artery and accompanying lymphatics are identified and spared. Schiff and associates recom-mend applying pressure to the testis after ligation is completed to determine whether an impulse can be felt in the ligated veins. The artery is identified by visualization of pulsations under higher (25×) magnification, application of 1% papaverine, use of a Doppler probe, and/or elevation with partial occlusion followed by release and visualization of pulsations within the vessel suspected to be an artery (Raman and Goldstein, 2004). The subinguinal approach is associated in rare cases with testicular atrophy (necrosis), which has not been reported for suprainguinal procedures (Diamond et al, 2009). The cause of necrosis is unclear but may be related to total venous occlusion, as may occur in some cases of sclerother-apy, or to compromise of both spermatic and vasal arteries.

Open/Laparoscopic Suprainguinal VaricocelectomyThe suprainguinal approach with spermatic artery ligation is a simple procedure performed either open or laparoscopically and associated with high success rates but also higher rates of hydro-cele formation. Lymphatic and/or artery sparing is associated with a reduction in the incidence of postoperative hydrocele, but iden-tification and preservation of these vessels may be difficult, even with magnification afforded by the use of laparoscopy. In retro-spective studies, Zampieri and associates (2007a, 2007b) report that artery sparing is associated with improved semen quality but no randomized prospective data exist that clearly define the effect of artery sparing on testicular function. Theoretically, testicular compromise may occur with spermatic artery ligation in patients with a history of previous inguinal surgery (Skoog et al, 1997) but was not reported to occur in a small series of boys after a laparoscopic Palomo procedure (Barqawi et al, 2002). Similarly, a risk to the testis exists after non–artery-sparing varicocelectomy with subsequent compromise to the vasal artery or vein, as in vasectomy.

In the standard open procedure, a muscle-splitting incision is made just medial to the anterior superior iliac spine and the


HERNIAS AND HYDROCELES

DefinitionsThe processus vaginalis and inguinal canal develop in both sexes in the first trimester of gestation (Barteczko and Jacob, 2000), although subsequent development of the processus vaginalis is more prominent in males to allow transinguinal passage of the testis. In males, the full length of the processus within and distal to the inguinal canal (the funicular process) becomes obliterated but the distal portion remains open as the tunica vaginalis within the scrotum. In an autopsy study, complete closure of the proces-sus vaginalis was observed in only 18% of full-term infants at birth (Mitchell, 1939). Contralateral exploration of 1965 children with a unilateral inguinal hernia revealed that the processus vaginalis was patent in 63% of patients younger than 2 months and about 40% of those 1 to 2 years of age, with similar frequency up until age 16 (Rowe et al, 1969). The time frame for closure of the proces-sus vaginalis in individuals without a hernia is not clear; however, the incidence of incidental patency observed in older children and adults at autopsy or laparoscopy is about 20% (Ajmani and Ajmani, 1983; van Wessem et al, 2003).

Persistent patency of all or a portion of the processus vaginalis within the inguinal canal may but does not always result in a symptomatic hernia or hydrocele (Fig. 132–6). If the processus remains widely patent, allowing passage of abdominal viscera, a clinical indirect inguinal hernia is present extending into the canal, labium, or scrotum. If fluid alone passes into a patent pro-cessus vaginalis and surrounds the testis within the tunica vagi-nalis, a communicating hydrocele is present (see Fig. 132–6A). Other forms of hydrocele include a spermatic cord hydrocele, which is associated with obliteration of the processus distally and in some cases proximally (see Fig. 132–6B and C), and noncom-municating simple scrotal hydrocele or abdominoscrotal hydrocele. Partial closure of a communicating sac may occur within the canal, producing both a proximal hernia and a distal noncommunicating hydrocele. Simple patency of the processus vaginalis is required but not sufficient for development of a hernia or communicating hydrocele.

Epidemiology and PathogenesisThe risk of pediatric hernia is highest in neonates, particularly premature boys; in contrast, the prevalence of hydrocele varies with age and etiology. Hydroceles that persist or first appear after birth are more likely to be associated with hernias, whereas those that disappear in infancy or appear at or after puberty are more commonly noncommunicating and due to delayed fluid absorp-tion or abnormal fluid dynamics within the tunica vaginalis. Rare causes of nonpainful hydrocele include tumor or inflammatory processes within the scrotum.

Inguinal Hernia and Communicating HydroceleThe incidence of inguinal hernia in childhood is 1% to 5%, with a male to female ratio of 5 to 10 : 1 and an increased propensity for right-sidedness, unilaterality (75% to 90%), and occurrence in premature infants (up to 30%) as noted for cryptorchidism (Jones et al, 1998; Kapur et al, 1998; Brandt, 2008). A clinical hernia or hydrocele may present at any time during childhood, but the average age in most large series is 3 to 4 years, although a third of pediatric hernias present in the first few months of life (Kapur et al, 1998). The vast majority of pediatric hernias are indirect inguinal hernias, although direct and femoral hernias also occur.

than open or laparoscopic procedures (see Table 132–5) and require significant radiation exposure. Venous occlusion is achieved in retrograde procedures using sclerosants such as 3% sodium tetradecyl sulfate or polidocanol, with or without intra-vascular coils or balloons. The procedure can be accomplished under local anesthesia and is typically performed at centers with expertise in interventional radiology. In series comprised primar-ily of children and adolescents the procedure is reported to be unfeasible for technical reasons in 5% to 22% of cases; and with varying degrees of follow-up (rarely more than 1 or 2 years), rates of persistence or recurrence are 6% to 35%. Self-limiting complications include pain, epididymo-orchitis, phlebitis, or scrotal swelling; partial testicular atrophy and hydrocele occur rarely. Antegrade techniques entail use of a small subinguinal or upper scrotal incision, isolation of a vein or veins amenable to cannulation with or without fluoroscopic confirmation of ante-grade flow into the internal spermatic vein, and injection of a sclerosant followed by ligation of the vein (Ficarra et al, 2004; Zaupa et al, 2006; Carmignani et al, 2009). This also can be performed under local anesthesia, and success rates are reported to be 4% to 12%, lower than for retrograde sclerotherapy, but complications are similar. Recently, Lebed and colleagues (2008) reported adjuvant use of sodium morrhuate sclerotherapy at the time of subinguinal or inguinal varicocele repair with or without use of the operating microscope. Their reported recurrence rate overall is similar to that reported for the subinguinal open approach alone, although they suggest that the additional use of a sclerosant may reduce the risk of recurrence owing to unrec-ognized proximal collateral veins.

Key Points: Varicocele

● The prevalence of adolescent varicocele is 8% to 16%, similar to that found in adults.

● Susceptibility to varicocele is determined by genetic predis-position, a tall, thin body habitus, and/or intrinsic venous abnormalities.

● Pain is the presenting complaint in less than 10% of adoles-cents with varicocele.

● Treatment of adolescent varicocele should be selective, because about 85% of adults with varicocele do not present with problems related to fertility.

● Ultrasonography is the most sensitive method for determin-ing volume discrepancy between testes, and the Lambert formula (length × width × depth × 0.71) is preferable for volume calculation.

● A 15% to 20% reduction in volume (hypotrophy) of the affected testis is common in boys presenting with varicocele; hypotrophy resolves in 55% to 70% of cases after varicocele repair but may also improve spontaneously with progression through adolescence.

● Hypotrophy but not varicocele grade is inversely correlated with semen quality in some series, but postoperative testicu-lar catch-up growth does not necessarily imply improved semen quality.

● Testicular hypotrophy involving the affected or both testes, abnormal semen analysis, and pain are current indications for adolescent varicocele repair.

● Laparoscopic or microscopic subinguinal artery- and lymphatic-sparing techniques for varicocele repair are asso-ciated with the lowest risk of both recurrence and hydrocele.


A DCBFigure 132–6. Anatomy of the processus vaginalis in hydrocele. A, Normal closure of the processus vaginalis; straight arrows indicate the funicular process; curved arrow is the tunica vaginalis. B, Communicating hydrocele with complete patency of the processus vaginalis; C, Funicular hydrocele with distal closure of the processus vaginalis; communication with the peritoneal cavity may also result in hernia.D, Encysted hydrocele of the spermatic cord. (From Martin LC, Share JC, Peters C, Atala A. Hydrocele of the spermatic cord: embryology and ultrasonographic appearance. Pediatr Radiol 1996;26:528–30.)

In a large series of 6361 consecutive pediatric hernias treated at a single institution, 19% were associated with hydroceles (70% scrotal only, 26% cord, and 4% both), although this may reflect referral bias (Ein et al, 2006).

Newly apparent hydroceles may be associated with a proces-sus vaginalis that is freely communicating proximally but closed at some level along the cord (see Fig. 132–6) with or without encysted or multiloculated segments (Martin et al, 1996). Most are asymptomatic, but rarely a portion of the sac or hydrocele may undergo acute torsion (Tillett et al, 2006). Although the circumference of the sac as measured at surgery tends to be smaller in communicating hydroceles as compared with hernias, the predictive value of this finding is limited (Tanyel et al, 2000). In an unusual observational study, 59% of 302 newly identified hydroceles presenting between 1 and 18 (mean 4.4) years of age were clinically communicating, that is, with a clear history of fluctuation, and 6% were spermatic cord hydroceles (Christensen et al, 2006). Seventy (65%) of the apparent non-communicating and 5 (29%) of the cord hydroceles were observed without surgery and, of these, 39 and 3, respectively, appeared to resolve spontaneously during follow-up. However, surgical findings were not reported in this series so the overall frequency of processus vaginalis patency in these patients is not known. In several series of all boys undergoing hydrocele repair during a defined period, the processus vaginalis was completely obliter-ated in 0% to 22% of cases (Elder, 1992; Barthold and Redman, 1996; Han and Kang, 2002). These data indicate that the majority of new hydroceles occurring after birth and before puberty are associated with a patent processus vaginalis.

Noncommunicating HydrocelesSimple hydroceles not associated with hernias occur in both infancy and in older boys. Stable, nonfluctuating scrotal hydro-celes that occur in at least 5% in male neonates (Osifo and Osaigbovo, 2008) are presumably related to delayed closure of the processus vaginalis, are typically bilateral, and often resolve with time as the processus closes in the perinatal period and reabsorp-tion of tunica vaginalis fluid occurs. Similarly, the majority of hydroceles occurring at or after puberty are noncommunicating, although the exact proportion that are associated with a hernia

and the overall incidence of hydrocele in this population are unclear. In a study specifically relating patient age to patency of the processus vaginalis, Wilson and associates (2008) studied 101 boys from birth to 20 years of age (mean 5.7) presenting with hydrocele and noted patency in 29% and 88% of those older and younger than 10, respectively.

Genetic and Other Risk FactorsThe risk of inguinal hernia during childhood is increased in fami-lies, with a 28% risk in other family members and a higher relative risk in first-degree relatives (6.9) and particularly female siblings (17.8) of affected girls (Gong et al, 1994; Jones et al, 1998). Detailed pedigree analysis suggests dominant inheritance with reduced penetrance and sex influence. The gene(s) influencing susceptibility to congenital (indirect) inguinal hernia remain unknown but may overlap with those determining risk of crypt-orchidism because there is overlap in familial risk and in suscep-tibility factors for both traits. Congenital hernia and cryptorchidism are both associated with low birth weight, bladder exstrophy, epididymal anomalies, connective tissue disorders, cystic fibrosis, posterior urethral valves (Heikkila et al, 2008), and, in some studies, increased risk for testicular cancer (Pottern et al, 1985; Tollerud et al, 1985). Inguinal hernia is also a component of over 200 syndromes (80 also include cryptorchidism; Winter-Baraitser Dysmorphology Database, http://www.lmdatabases.com) and is more common in patients with ventriculoperitoneal shunts and other causes of ascites (Grosfeld et al, 1991).

DiagnosisThe most common presentations of pediatric inguinal hernia are inguinal or inguinoscrotal swelling in infancy and new onset of scrotal swelling in older children. Typically the child is asymp-tomatic, but the swelling is observed with crying or straining or may be preceded by a bout of vomiting, constipation, or respiratory illness. Communicating hydroceles usually fluctuate and may appear larger after activity or at the end of the day as compared with early morning. Rarely acute scrotal swelling is accompanied by pain, and other causes of acute scrotum must be ruled out. Nausea, vomiting, and in some cases fever suggest incarceration. The risk of incarceration is highest in infancy,

http://www.lmdatabases.com


particularly in ex-premature males, and is uncommon after 5 years of age.

Multiple approaches are described to increase intra-abdominal pressure and confirm the presence of a hernia on physical exami-nation, including immobilization of the extremities to induce crying in infants, and coughing, blowing bubbles, or blowing up balloons and laughing in older children (Brandt, 2008). Suggestive physical findings include asymmetrical widening of the inguinal region and the “silk glove” sign, which is elicited by palpation of the spermatic cord over the pubis, resulting in a sensation of layers of the sac slipping over each other. Hydroceles often appear bluish, can be transilluminated, and may be partially or fully decompressable. Swelling that extends into and above the ingui-nal canal is more likely a hernia if reducible and/or if crepitus associated with bowel loops is present. In contrast, abdomino-scrotal hydroceles are ballotable on bimanual scrotal-abdominal examination and cannot be decompressed. Attention should be paid to palpation and documentation of the position of the ipsi-lateral testis. Additional parental observation and/or office exami-nations may be warranted if an inguinal bulge is not elicited or if there is no clear history of fluctuation of an asymptomatic scrotal hydrocele.

Inguinoscrotal ultrasonography can be used to differentiate bowel loops from simple fluid and to visualize the testis, patent processus vaginalis, or hernia sac. If the testis is not palpable, ultrasonography is useful in determining whether a tumor with secondary hydrocele or cryptorchidism is present. Preoperative knowledge of these entities is critical for defining preoperative evaluation, parental counseling, and surgical approach. Toki and coworkers (2003) classified the appearance of the internal ring by ultrasonography. Using visualization of an open processus vagina-lis of at least 20 mm in length as a criterion for contralateral inguinal exploration surgery, they observed a reduced risk of meta-chronous hernia after 2 years’ follow-up. Although its use is not routine, ultrasonography may be helpful in defining fluid or intra-abdominal content in the inguinal canal with increased abdomi-nal pressure in patients with suspected hernia or communicating hydrocele and questionable findings on routine examination. Alternatively, laparoscopy can be used to diagnose and treat ingui-nal hernia, as discussed later.

Associated Pathologic ProcessesSeveral diseases associated with inguinal hernia and/or similar presentation require a high index of suspicion for diagnosis. Incomplete testicular descent may coexist with clinical hernia and should be excluded or corrected at the time of repair. Other genital anomalies such as polyorchidism, transverse testicular ectopia with or without persistent müllerian ducts, and splenogonadal fusion may present at the time of hernia repair. Abnormal epididymal-testicular attachment correlates with degree of closure of the processus vaginalis (Elder, 1992; Barthold and Redman, 1996). In phenotypic females, rare cases of androgen insensitivity syndrome may be identified at the time of hernia repair by exami-nation of the abdominal or inguinal gonads, careful genital exami-nation, and calibration of vaginal length.

Surgical RepairOnce a diagnosis of inguinal hernia or communicating hydrocele is made, timely elective repair is indicated. If ipsilateral cryptor-chidism is present in an infant with a clinically apparent hernia, repair should proceed without observation for spontaneous

testicular descent. Repair is performed as an outpatient procedure except in cases of ex-premature infants, who receive apnea moni-toring in the hospital overnight if less than 50 to 52 weeks’ post-conceptional age. Some authors recommend delaying surgery until after this time point versus proceeding with repair before discharge from the hospital, although the reliability of the family and the higher risk of incarceration in infants (Stylianos et al, 1993; Chen et al, 2009) should be taken into account. In contrast, neonatal hydroceles should be observed for spontaneous resolu-tion, because they are not associated with a persistently patent processus vaginalis in the majority of cases and most resolve in the first or second year of life.

Standard Inguinal Hernia RepairThe traditional inguinal approach to hernia/hydrocele repair is the preferred approach for most surgeons in view of a high success rate, low morbidity, limited degree of associated pain, and good cosmesis. A small incision in Langer’s lines at or below the inguinal skin crease and superolateral to the pubic tubercle is made (Kogan, 2007). The external oblique fascia is exposed and incised through the external inguinal ring with care to avoid the ilioinguinal nerve. The spermatic cord is exposed and the hernia sac visualized and dissected free, open or closed, from the adjacent spermatic cord structures, which is facilitated by longitudinal incision of the external spermatic fascia. A long-held principle is the importance of high ligation of the hernia sac at the level of the internal inguinal ring to avoid risk of recur-rence (Grosfeld et al, 1991). If the sac is large or thickened, it should be opened before transection to identify prolapsed bowel, omentum, or a sliding component, which if present is reduced before closure. Tightening of the internal ring with absorbable suture is recommended in cases of significant widening (Ein et al, 2006; Brandt, 2008). If a loculated hydrocele is present, it is exposed from above after distal mobilization of the overly-ing cremaster muscle and fascia in a bloodless plane and incised longitudinally for complete decompression. If the testis is easily visualized, the surgeon should remove any testicular or epididy-mal appendage that is present. The testis is then grasped and pulled caudally to a dependent scrotal position and if not depen-dent an orchidopexy should be performed. In pubertal boys with hydrocele, a primary inguinal approach is preferred if there is clinical evidence of a communicating hydrocele; otherwise a transscrotal hydrocele repair is performed as in adults and an inguinal incision made only if a proximal communication is identified. Pain control is augmented by an ilioinguinal or caudal nerve block.

Early postoperative complications are rare after repair of pedi-atric hernia via an inguinal approach. The reported risk of recur-rence is 0.7% to 1% and may be related to failure of high ligation of the sac, size of the hernia, injury to the floor of the canal or sac, and/or comorbid conditions that affect wound healing (Gros-feld et al, 1991; Vogels et al, 2009). Wound infection and bleeding are similarly rare. Persistence of a hydrocele is very rare after decompression at the time of hernia repair (0.1% in the series by Ein and associates [2006]) and should be observed for spontaneous resolution for at least 1 year. If persistent, secondary scrotal hydro-cele repair is indicated or reoperative hernia repair is required if fluctuation suggests a recurrent hernia.

Complications related to the genital tract including secondary cryptorchidism, testicular atrophy, and vasal injury occur, but their incidence is not well defined. Some cases of undescended testis after previous hernia repair may reflect milder primary forms of incomplete descent that were not clinically evident


preoperatively. Patients should be examined postoperatively on a yearly basis to ensure that testicular position does not change. Likewise, close observation is needed to identify testicular atrophy. The risk of this complication in general is unknown, but a 0.3% incidence was reported in the large single center series of Ein and associates (2006). Excised hernia sac tissue reportedly contains portions of vas deferens in 0.13% to 0.3% of cases, although embryonal remnants not representing true ductal structures are much more common (1.5% to 2.9%) (Popek, 1990; Partrick et al, 1998; Steigman et al, 1999). However, these data reflect results at high-volume pediatric centers and may be lower than those appli-cable to other practices. The risk of vasal injury may also be higher in young infants and/or cases of incarceration. Of course, injury to the vas may occur without transection and be manifest as vasal obstruction later in life. Indeed, pediatric hernia repair was the most common cause of vasal obstruction in a series of men pre-senting to a large infertility practice; the prevalence of this outcome in all boys undergoing repair using present surgical tech-niques is not known but in a review of older publications was estimated to be 0.8% to 2% (Sheynkin et al, 1998). Manipulation or stretching of the vas in adult rats (reviewed in Brandt, 2008) can produce obstructive lesions or even testicular atrophy, but the degree to which these effects are applicable to humans is unknown. The overall risk of this significant complication and its potential to cause clinical subfertility is undefined because many cases may be unilateral.

Scrotal Approach to Inguinal Hernia RepairConcurrent with recent reports advocating a scrotal approach to orchidopexy, some authors suggest a similar approach to inguinal hernia and communicating hydrocele (Lais and Ferro, 1996; Fearne et al, 2002; Gokcora and Yagmurlu, 2003). Initial data suggest no major differences in the rates of success or degree of morbidity using this approach compared with standard inguinal surgery. Fearne and colleagues (2002) ligated the processus vagi-nalis at the level of the external inguinal ring, with one recurrence in 195 repairs in boys followed a mean of 13 months postopera-tively. Potential issues related to the level of sac ligation based on technique and patient age have not been fully addressed (Wilson et al, 2008). Long-term data are needed to define the benefits and limitations of the scrotal approach to inguinal hernia repair.

Laparoscopic Inguinal Hernia RepairWith increase in the use of minimally invasive surgical techniques in recent years, laparoscopic repair of hernias in children has become an alternative to the standard open procedure. Two major techniques are reported: peritoneal closure of the defect (Schier, 2006) and an extraperitoneal approach (Takehara et al, 2006; Endo et al, 2009).

With experience, the operative time may be similar to open surgery; however, even in very large series the risk of recurrence (as high as 4%) is higher than with open repair but may decrease with increasing experience (Saranga Bharathi et al, 2008) and appears to be lower (<1%) with extraperitoneal approaches. However, Schier observed that some recurrences are not associated with an open internal inguinal ring on laparoscopic reexploration and may be related to a lipoma within the inguinal canal that would normally be addressed in an open repair (Schier, 2007a). Decreased pain and operative time after laparoscopic as compared with open repair was reported in one small prospective study (Chan et al, 2005), but the opposite conclusion was reached in a similar study (Koivusalo et al, 2009). The risk of persistence after

laparoscopic repair of communicating hydrocele and long-term potential for vasal obstruction has yet to be addressed in the lit-erature. However, the risk of testicular atrophy appears to be low in reported series. Laparoscopy has also been advocated to facili-tate repair of recurrent and incarcerated hernias (Saranga Bharathi et al, 2008).

Assessment of the Contralateral Internal RingA long-standing controversy relating to pediatric inguinal hernia repair is the need for identification and repair of a contralateral patent processus vaginalis. In the past, contralateral exploration was used routinely in subsets of patients considered at higher risk for metachronous hernia based on age, prematurity, gender, or associated disease. The processus is patent on the opposite side in 40% of children with unilateral clinical hernia undergo-ing laparoscopy (Miltenburg et al, 1998), up to 60% of contra-lateral explorations (Tackett et al, 1999), and in 20% of adults at autopsy (Ajmani and Ajmani, 1983). In contrast, two systematic literature analyses conclude that the risk of developing a con-tralateral hernia during follow-up is about 10%, and the majority of these cases present within 5 years with a trend toward decreased risk with age (Miltenburg et al, 1997; Ron et al, 2007). In a prospective study no consistent factors were associated with sig-nificantly increased risk of metachronous hernia, except perhaps a previous history of incarceration (Tackett et al, 1999). The risk of contralateral hydrocele after unilateral communicating hydro-cele repair is not known but is likely lower. Consequently, even selective exploration or repair of the opposite side in cases of unilateral pediatric inguinal hernia is no longer recommended. An exception may be children at sig-nificantly higher anesthetic risk (Tackett et al, 1999). For surgeons who perform laparoscopic herniorrhaphy, contralateral repair is less invasive; and thus many surgeons recommend repair of an open processus vaginalis identified at the time of laparoscopy. However, the pros and cons of such an approach should be reviewed with the patient’s family with the knowledge that an open internal ring is not equivalent to an inguinal hernia (Schier, 2007b).

Abdominoscrotal HydroceleAbdominoscrotal hydrocele is an unusual form of noncommuni-cating hydrocele, comprising 1.25% of all pediatric hydroceles in a large series (Avolio et al, 2000). Unlike the typical neonatal hydrocele, it is large and tense, and bimanual examination usually confirms the presence of a ballotable abdominoscrotal mass. Ultra-sonography can be used to visualize the degree of proximal exten-sion and the testis but is not required in typical cases (Belman, 2001). Abdominoscrotal hydrocele usually presents in the neona-tal period or in infancy and may initially be limited to the scrotum with progressive enlargement over time (Celayir et al, 2001; Cuervo et al, 2009). In other cases, spontaneous resolution (Upadhyay et al, 2006) or improvement (Cozzi et al, 2008) was reported. In the larger published series, abdominoscrotal hydro-cele was bilateral in about 30% of cases (Ferro et al, 1995; Nagar and Kessler, 1998; Belman, 2001; Bayne et al, 2008; Cozzi et al, 2008). In addition, associated diagnoses may include ipsilateral or contralateral cryptorchidism, contralateral hernia, hydrocele, or vanishing testis. A single case of associated malignant mesothe-lioma was reported (Velasco et al, 1988). Progressive proximal enlargement, characteristics of the hydrocele fluid, and nonpa-tency of the processus vaginalis suggest that the most likely cause is enlargement and extension of a scrotal hydrocele into the


complaint in pediatric urology. The signs and symptoms of dis-eases associated with acute scrotal pain vary markedly with exten-sive diagnostic overlap. Although some clinical features are more reliable than others, few if any details of history, physical exami-nation, or imaging are absolutely diagnostic of particular intra-scrotal pathologic processes. Thus the clinician should make a prompt diagnosis based on all the available findings, which may include those obtained at scrotal exploration, particularly if the duration of pain is short (<6 hours), the presenting signs lack suf-ficient reliability, or the diagnosis remains unclear after clinical evaluation.

Etiology and Differential DiagnosisIndividuals with many types of inguinoscrotal pathology may present with acute scrotal pain or swelling (Table 132–6). In some patients with scrotal pathology the pain may be localized to the inguinal or abdominal regions or poorly localized, particularly in younger children. Historical information of potential importance includes the onset, quality, duration, and consistency of pain; history of previous episodes; exacerbation with activity; presence

retroperitoneal or properitoneal space after the processus has closed. Bayne and associates (2008) reported that abdominoscrotal hydrocele fluid is exudative and theorize that increasing size and pressure lead to lymphatic obstruction and worsening over time. Massive enlargement in some cases may extend into the upper abdomen and be associated with hydroureteronephrosis, lower extremity edema, or appendicitis (reviewed by Cuervo et al, 2009). Chamberlain and colleagues (1995) first reported dysmorphic elongation of the testis in an infant with bilateral abdominoscrotal hydrocele, and others have confirmed this observation, presum-ably related to high pressures within the sac (Bayne et al, 2008).

The surgical approach to this rare entity is controversial, related to what is perceived as a higher risk to the cord and testis during repair because of the size of the lesion and the young age of the patient. The traditional approach to repair is via an inguinal inci-sion with proximal dissection of the sac from its abdominal attachments and distal complete or partial mobilization, with or without orchidopexy. Some authors use orchidopexy routinely, irrespective of the preoperative position of the testis (Nagar and Kessler, 1998; Bayne et al, 2008). Failure to excise the abdominal portion of the sac may lead to its persistence. Alternative, rarely reported approaches to the intra-abdominal portion include a higher or midline (for bilateral cases) incision or laparoscopic decompression followed by inguinal excision (Serels and Kogan, 1996; Abel et al, 2009). Some authors recommend leaving a strip of the lining of the sac along the cord to avoid injury to the vas or vessels (Ferro et al, 1995; Cuervo et al, 2009), a rarely reported complication (Serels and Kogan, 1996). Tightening of a patulous internal ring is described, but the necessity for this maneuver is unclear because the processus vaginalis is invariably closed and the risk for postoperative hernia appears to be rare. Because the procedure may be prolonged and tedious, some surgeons use scrotal drains, preoperative antibiotic prophylaxis, and postopera-tive hospitalization.

An alternative simplified surgical technique for abdominoscro-tal hydrocele that may be underutilized is the primary scrotal approach described by Belman (2001). The hydrocele is approached through a scrotal incision, and extensive plication without exci-sion is performed as for the Lord procedure. Prolonged scrotal edema associated with involution of the sac is expected, but this approach is appealing because the processus vaginalis is closed in most if not all cases and dissection is limited. Although Belman did not present detailed outcome data using this approach, Cozzi and colleagues (2008) reported reduced morbidity and similar efficacy for the scrotal as compared with the inguinal approach in 18 cases (5 bilateral). This latter series is unique in that detailed outcome was reported in 13 and 5 patients undergoing inguinal and scrotal surgery, respectively, with a median follow-up of 4 years. Persistent scrotal swelling, hematoma, and undescended and/or hypoplastic testis were reported in 11 of 13 inguinal cases and infection in 2 scrotal cases. These authors also observed that 78% of testes were dysmorphic preoperatively but that 15 of 18 regained normal shape and size postoperatively, suggesting that fluid pressure dynamics contribute to this finding. The prognosis for adult testicular function in abdominoscrotal hydrocele and the risk of possible long-term postoperative complications remain unknown.

ACUTE SCROTUMThe new onset of pain, swelling, and/or tenderness of intrascrotal contents is referred to as acute scrotum and is a common presenting

Table 132–6. Differential Diagnosis of Pediatric/Adolescent Acute Scrotal Pain

Appendage torsionAppendix testisOther appendage (epididymis, paradidymis, vas aberrans)

Spermatic cord torsionIntravaginal, acute or intermittentExtravaginal

EpididymitisInfectious

Urinary tract infectionSexually transmitted disease?Viral

Sterile or traumaticScrotal edema/erythema

Diaper dermatitis, insect bite, or other skin lesionsIdiopathic scrotal edemaEarly Fournier gangrene

OrchitisAssociated with epididymitis with or without abscessVasculitis (e.g., Henoch-Schönlein purpura)Viral illness (mumps)

TraumaWith hematocele or scrotal contusionWith testicular rupture

Hernia/hydroceleInguinal hernia with or without incarcerationCommunicating hydroceleEncysted hydrocele with or without torsionAssociated with acute abdominal pathology (e.g., appendicitis,

peritonitis, splenic rupture)Varicocele

With painWith acute rupture or thrombosis

Intrascrotal massCystic dysplasia or tumor of testisEpididymal cyst/spermatocele or tumorOther paratesticular tumors

Musculoskeletal pain due to inguinal tendonitis or muscle strainReferred pain (e.g., ureteral calculus or anomaly)


of associated symptoms such as nausea, vomiting, irritative voiding, penile discharge, fever, and other illness; and trauma, sexual, and immunization history. In a large series of surgically treated pediatric patients, appendix testis torsion is the most common diagnosis (40% to 60%), followed by spermatic cord torsion (20% to 30% excluding neonates), epididymitis (5% to 15%), and other or no pathology (~10%) (Anderson and Giaco-mantonio, 1985; Sidler et al, 1997; Van Glabeke et al, 1999; Mushtaq et al, 2003; Murphy et al, 2006; Makela et al, 2007). In general, appendage torsion is most common after infancy and before puberty whereas epididymitis and spermatic cord torsion are most common in the perinatal and pubertal periods. However, any of these diseases can occur at any time during childhood and adolescence.

Spermatic Cord TorsionAcute spermatic cord torsion with reduction or cessation of blood flow to the testis may occur in susceptible individuals. Intravaginal spermatic cord (testicular) torsion occurs when the testis twists within the tunica vaginalis, whereas extravaginal testicular torsion occurs in the perinatal period before fixation of the tunica vagi-nalis within the scrotum.

Acute Intravaginal Spermatic Cord TorsionPredisposing Factors. The anatomic abnormality predisposing to

torsion of the spermatic cord, the bell-clapper deformity, was identified in 12% of males in an autopsy series (Caesar and Kaplan, 1994a). This anatomic variant is due to partial or complete failure of fusion of the tunica vaginalis along the epididymis, resulting in incomplete attachment of the testis/epididymis to the scrotum (Fig. 132–7) or to an abnormally wide attachment of testis to epididymis. Despite the high prevalence of the bell-clapper defor-mity, the prevalence of torsion is much lower, reported as 8.6 per

100,000 males aged 10 to 19 per year in the United States (Mansbach et al, 2005) with some evidence for a familial predis-position (Cunningham, 1960; Collins and Broecker, 1989). The direct precipitating event in susceptible individuals is unknown but may include cold temperature, sudden movement or trauma with activation of the cremasteric reflex, and/or rapid growth of the testis at puberty. Some studies suggest an inverse correlation between the prevalence of torsion and atmospheric temperature (Srinivasan et al, 2007; Lyronis et al, 2009). Undescended testes are at higher risk for torsion, although the prevalence in this group as a whole is low. Rarely, torsion may occur after previous orchi-dopexy for cryptorchidism or testicular torsion. In these cases the etiology may be related to failure of suture (absorbable or nonab-sorbable) fixation of a testis that remains within an intact tunica vaginalis (Redman and Barthold, 1995; Frank and O’Brien, 2002; Mor et al, 2006).

Clinical Presentation. Although intravaginal testicular torsion may occur in any young male, the peak age at occurrence is 12 to 16 years, with additional cases occurring in postpubertal males and 86% to 93% occurring after age 10 (Anderson and Giaco-mantonio, 1985; Sidler et al, 1997; Mushtaq et al, 2003; Mans-bach et al, 2005; Murphy et al, 2006; Makela et al, 2007). The prevalence of testicular torsion in these retrospective surgical series is 20% to 30% with left-sided predominance; however, in another large series, testicular torsion comprised only 6% of 626 patients younger than 17 years of age (Lam et al, 2005). Very rarely, torsion occurs bilaterally. Classically, patients complain of sudden, severe scrotal pain that may occur at rest, with activity or sports, or during sleep, and a history of previous similar epi-sodes of pain, usually on the ipsilateral side, may be present. Alternatively, patients may have milder, less acute, or even no scrotal pain or may have inguinal or abdominal pain. The patient may report direct scrotal trauma, which may precipitate twisting of the cord, a historical feature that should not alter the diagnostic

Figure 132–7. Variable degrees of bell-clapper deformity show normal (A), partial (B), and complete (C) variants. Angles drawn represent variations in attachment of tunica vaginalis. (From Bentley DF, Ricchiuti DJ, Nasrallah PF, McMahon DR. Spermatic cord torsion with preserved testis perfusion: initial anatomical observations. J Urol 2004;172:2373–6.)

A B C


approach to the patient (Lrhorfi et al, 2002). Most retrospective series report that boys presenting early, especially within 6 hours of onset of pain, are more likely to have testicular torsion than other intrascrotal pathology. Nausea and vomiting occurs in 10% to 60% of boys with intra-vaginal testicular torsion and may be more common in pubertal and postpubertal boys (Williamson, 1976; Knight and Vassy, 1984; Jefferson et al, 1997; Sessions et al, 2003; Makela et al, 2007). Scrotal edema and erythema may be present depending on the duration or degree of torsion. Dysuria and fever are occasionally reported.

The most common physical findings are generalized testicular tenderness and absence of the cremasteric reflex. This genitofemo-ral reflex arc is normally present in boys after 2 years of age (Caesar and Kaplan, 1994b), is elicited by scratching the inner thigh with resultant elevation of the testis within the scrotum, and is one of the most useful and specific signs ruling out testicular torsion. Although some studies suggested that the reflex is reduced or absent in all cases of testicular torsion (Caldamone et al, 1984; Rabinowitz, 1984; Kadish and Bolte, 1998) the reflex was intact in up to 10% of proven cases of torsion (Hughes et al, 2001; Nelson et al, 2003; Karmazyn et al, 2005; Murphy et al, 2006). A normal cremasteric reflex is strongly correlated with intact blood flow to the testis but does not infallibly indicate normal testicular perfusion, especially if the clinical pre-sentation is otherwise suggestive of torsion. Similarly, a blue dot sign, considered specific for appendix testis torsion, has been reported in association with normal scrotal ultrasound find-ings in a case of testicular torsion (Murphy et al, 2006). In some cases elevation of the testis from its dependent scrotal position, abnormal lie, or anterior epididymal position, thickening of the cord suggestive of a twist, testicular induration, loss of boundaries between the testis and epididymis, scrotal edema, and/or ery-thema are present but vary depending on the age of the patient and duration of torsion but may be helpful in supporting the diagnosis of torsion.

Diagnostic Studies. Urinalysis is performed to identify pyuria and/or bacteriuria, findings that may be associated with epi-didymitis, or hematuria, which may indicate urinary tract cal-culus. Although the findings on urinalysis are usually normal in cases of testicular torsion, pyuria may be present and create diagnostic confusion (Anderson and Giacomantonio, 1985; Jef-ferson et al, 1997). Scrotal imaging is used more routinely in recent years, particularly in cases of prolonged (>24 hours) pain associated with preservation of the cremasteric reflex and severe scrotal swelling with loss of intrascrotal landmarks. Radionuclide imaging is primarily of historic interest owing to lack of speci-ficity and prompt availability at many centers. CDUS can be used to visualize testicular architecture and intraparenchymal blood flow; and with the improved sensitivity of current tech-nology flow is visible in most normal testes, irrespective of age. CDUS findings consistent with established testicular torsion include reduced or absent Doppler waveforms, parenchymal heterogeneity, and/or altered echotexture compared with the contralateral testis (Fig. 132–8). Kaye and colleagues (2008b) reported that all testes with a heterogeneous echogenicity as shown by CDUS were necrotic and were removed or atrophied after orchidopexy, whereas homogeneous echogenicity predicted a reduced risk of orchiectomy but long-term outcome was not provided. Enthusiasm for CDUS as a reliable modality to exclude testicular torsion was based on data suggesting that this approach is highly reliable (Kass et al, 1993b). With further experience and possibly due to enhanced detection of flow with newer

equipment and/or user-dependent characteristics, the estab-lished sensitivity of CDUS in confirming decreased or absent blood flow in proven cases of spermatic cord torsion is a disappointing 63% to 90% (Steinhardt et al, 1993; Stehr and Boehm, 2003; Bentley et al, 2004; Kalfa et al, 2004; Karmazyn et al, 2005). In reviewing false-negative cases in their series and those of others, Bentley and coworkers (2004) observed that arterial blood flow can persist in the presence of established torsion (see Fig. 132–8) and theorize, based on pre-liminary data, that preservation of flow may be more likely in males with a preexisting thick spermatic cord. Cassar and col-leagues (2008) retrospectively evaluated Doppler waveforms in cases of torsion with decreased or preserved testicular flow and observed subtle waveform abnormalities, including increase or decrease in amplitude relative to the normal testis and reversal of diastolic flow. These may help increase the sensitivity of CDUS in cases of torsion. In addition, increased epididymal size and/or echogenicity and altered epididymal vascularity, usually absent or reduced but occasionally increased, may provide addi-tional support for the diagnosis of torsion (Nussbaum Blask and Rushton, 2006).

High-resolution ultrasonography (HRUS) of the length of the spermatic cord using a 10- to 20-mHz probe may provide a prom-ising new approach for identifying torsion in equivocal cases. Kalfa and colleagues (2004) used HRUS in children and young adults to directly identify the twisted cord superior to the testis. They visualized the cord twist as a 1- to 3-cm snail-shaped mass in 43 patients, and confirmation was suspected but difficult in an additional patient with an inguinal testis. Conversely, a com-pletely linear cord is visualized in nontorsion cases. In a multi-institutional retrospective series of 919 cases of acute scrotum, these authors reported HRUS visualization of a cord twist in 96% of 208 surgically proven torsion cases and 100% sensitivity of the combination of cord twist and/or reduced blood flow in diag-nosing torsion (Kalfa et al, 2007). However, Karmazyn and coworkers (2005) observed normal testicular blood flow and no visible spermatic cord twist in 2 of 41 boys with partial or inter-mittent torsion. Although this technique is promising, prospective studies are needed with surgical confirmation of diagnoses and prolonged careful follow-up to ensure that it is reproducible in other settings and that varying presentations of torsion are not missed.

Potentially useful diagnostic modalities that have been studied in animal models but not yet tested clinically include contrast-enhanced pulse-inversion ultrasonography and infrared thermo-graphy. Pulse-inversion imaging in a rabbit model showed superior quantitative assessment of perfusion of the experimen-tally torsed testis as compared with conventional CDUS (Paltiel et al, 2006). In a sheep model an infrared thermographic camera showed significant reduction in scrotal temperature by 1 hour after 720-degree torsion and prompt normalization with detorsion (Capraro et al, 2008). Infrared thermography is presently used clinically for diagnosis of varicocele in adults (Nogueira et al, 2009).

Surgical Treatment and Findings. With increasing availability and use of urgent CDUS, and more recently HRUS, and the relatively low (6-30%) prevalence of testicular torsion in children and ado-lescents with acute scrotal pain, a strategy of managing essentially all patients surgically to confirm absence of torsion (Anderson and Giacomantonio, 1985; Watkin et al, 1996; Sidler et al, 1997; Mushtaq et al, 2003; Makela et al, 2007) has shifted toward selec-tive surgical exploration (Caldamone et al, 1984; Kass et al, 1993b; Kalfa et al, 2004; Lam et al, 2005). Most surgeons currently use


diagnostic techniques may in future more reliably support non-surgical treatment of the majority of boys presenting with an acute scrotum without torsion.

Some clinicians recommend preoperative manual detorsion based on the assumption that twisting of the testis occurs in a medial direction. However, in a retrospective review of 186 surgical explorations for torsion, Sessions and associates deter-mined that lateral twisting (Fig. 132–9) occurred in 33% and manual detorsion attempts in 30% of the total group failed to completely relieve the torsion in 32% of cases (Sessions et al, 2003). The resolution of symptoms after manual detorsion did not correlate with the presence or absence of persistent torsion.

this selective approach, but a minority continue to recommend urgent surgical intervention for all cases of acute scrotum to avoid any risk of inaccuracy associated with the clinical and imaging diagnosis of testicular torsion (Murphy et al, 2006). Indeed, most series report cases with atypical presentation and/or false-negative imaging in which surgical exploration was delayed and the testis lost, but the clinician’s goal should be to minimize the risk of such cases. When findings support or are suspicious for sper-matic cord torsion, emergent scrotal exploration is indi-cated and should not be delayed to obtain scrotal ultrasonography or any other diagnostic test. The increased sensitivity provided by HRUS and potentially newer noninvasive

Figure 132–8. Imaging of intravaginal spermatic cord torsion. A, Intermittent torsion. Color Doppler ultrasonography (CDUS) in a 14-year-old boy with 12 hours of right testicular pain and intact cremasteric reflex shows preserved arterial flow to testis at an initial emergency department visit and loss of flow and increased heterogeneity of right testicular parenchyma when patient returned with increased pain. Exploration confirmed 360-degree intravaginal torsion. B, Acute torsion with reduced arterial flow. CDUS in an 18-year-old boy with variable right testicular pain shows reduced arterial flow to testis and increased echogenicity on transverse view comparing both testes. Right epididymal hyperemia and enlargement were also noted. Exploration confirmed 540-degree torsion with prompt return of vascularity with detorsion. C, Prolonged torsion. CDUS in a case of a 9-year-old boy presenting with prolonged left testicular pain shows heterogeneous echotexture, absence of arterial or venous flow, and a hyperechoic parenchymal ring; testicular necrosis was found at scrotal exploration.

A1

C1

B1A2

A3

B2

B3

C2


Figure 132–9. A and B, Intravaginal spermatic cord torsion with a viable testis. Findings at scrotal exploration in a 15-year-old boy with less than 6 hours of intravaginal torsion, 360-degree lateral rotation of the cord, and a viable testis. Color Doppler ultrasonography showed reduced arterial flow.

A B

Jefferson and colleagues (1997) noted a similar frequency of resid-ual intraoperative torsion after attempts at manual detorsion. Therefore although this maneuver may be attempted, it should not delay transfer to the operating room for definitive detorsion and fixation of the testis.

After induction of anesthesia, the affected testis should be approached first through a hemiscrotal transverse or midline inci-sion. Once delivered, the surgeon should perform detorsion and document the number of cord rotations and the presence and degree of bell-clapper deformity. The testis is observed for improve-ment in color, but the decision to remove or retain the affected testis is subjective and, although based on the appearance of the testis, is likely also biased by the age of the patient and the degree and duration of torsion. A Doppler flow probe or incision of the tunica albuginea (Arda and Ozyaylali, 2001) with assessment of bleeding can be used to document intratesticular flow after detor-sion, but the usefulness of these maneuvers in predicting viability of the testis has not been validated. Kutikov and colleagues (2008) suggest that compartment syndrome may contribute to testicular injury based on the improved appearance and lower intraparen-chymal pressures they observed after detorsion and incision of the tunica albuginea. They covered the testicular defect with a vascularized tunica vaginalis patch to maintain lower intraparen-chymal pressure and reduce the likelihood of ongoing ischemia. The long-term outcome of these patients is not available, and larger prospective studies are required to determine the benefit of this approach.

The overall frequency of orchiectomy when testes appear non-viable after surgical detorsion is 30% to 70% in large pediatric studies (Sessions et al, 2003; Murphy et al, 2006; Makela et al, 2007; Kaye et al, 2008b) and 34% in a population-based review

of males aged 1 to 25 (Mansbach et al, 2005). Sessions and asso-ciates (2003) noted at operation that the median degree of rota-tion was 540 degrees in patients undergoing orchiectomy (38% of cases) and 360 degrees when the testis was salvaged, with a range of 180 to 1080 degrees in both groups. There is no clear-cut clinical evidence that orchidopexy or orchiectomy provides superior results in maximizing ultimate testicular function (see later). However, attempts should be made to salvage the testis if there is any sign of reperfusion after detorsion. The surgeon may biopsy questionably viable testes that are left in place to docu-ment the presence or absence of necrosis. Any testicular append-age should be removed. Intrascrotal fixation of the testis must be performed bilaterally because a contralateral bell-clapper deformity usually exists and may lead to metachronous torsion. Techniques of fixation that secure the testis within a subdartos pouch may reduce the risk of recurrent torsion within an intact tunica vaginalis if sutures between the testis and scrotal wall fail (Redman and Barthold, 1995; Frank and O’Brien, 2002; Mor et al, 2006). One approach allows oblit-eration of the tunica vaginalis and secure fixation of the testis without transparenchymal sutures within a scrotal pouch (Redman and Barthold, 1995). An incision is made in the upper third of the scrotum on each side. After delivery of the testis and eversion of the parietal tunica vaginalis along the cord, the cut edges of the inverted tunica are closed bilaterally with absorbable suture. This prevents retraction of the testis back into a tunica vaginalis–lined scrotal cavity. A subdartos pouch is created, and the testis is secured in the pouch by placement of sutures between the tunical layer covering the cord and the dartos. Follow-up for at least 6 months is mandatory to determine the presence and degree of testicular volume loss. For cases of testicular loss, prosthesis


episodes (Stillwell and Kramer, 1986; Williamson, 1976). These episodes typically begin and resolve rapidly, last minutes to hours, and may occur at any interval from days to months. In a retro-spective review of cases ultimately diagnosed as intermittent torsion, Hayn and associates (2008) observed that the frequency of pain episodes correlated with the risk for eventual persistent torsion and testicular loss in children and adolescents. Of 17 boys presenting emergently with ongoing torsion, 71% were diag-nosed on previous occasions with epididymitis or appendage torsion and 53% had acute or delayed testicular loss. Horizontal testicular lie may be present in patients with intermittent torsion (Schulsinger et al, 1991) but was documented in less than half of patients presenting either urgently or electively and was not seen in prepubertal males in the series of Hayn and associates (2008). Eaton and coworkers (2005) reported that the cremasteric reflex was absent in only 3 of 15 patients and that CDUS showed reduced or absent intratesticular blood flow in only 5 of 12 patients examined during a bout of pain. Six of 38 patients in this series had increased flow to the testis or epididymis. One fourth of patients had nausea and vomiting, a sign the authors suggested could be used to rule out epididymitis. Of those with complete surgical documentation, 15% did not have a bell-clapper deformity and 1 patient in the series continued to have pain postoperatively.

These reports underscore the difficulties inherent in identifica-tion and treatment of intermittent spermatic cord torsion, because patients may present with acute pain suggestive of torsion but with physical and imaging findings that appear normal as the torsion improves or resolves during the acute episode. The diag-nosis requires a high index of suspicion in males with recurrent bouts of pain. CDUS may be most helpful in the midst of pain symptoms, particularly if intratesticular blood flow is reduced, but if results are normal or increased may provide unwarranted reas-surance to the clinician. In cases of torsion-detorsion, prompt elective bilateral orchidopexy is indicated with the knowledge that in some cases absolute confirmation of the diagnosis may not be possible, and patients and parents should be advised that pain symptoms could persist postoperatively.

Extravaginal Spermatic Cord Torsion (Perinatal Testicular Torsion)Perinatal spermatic cord torsion is due to rotation of the testis, entire cord, and tunica vaginalis before established fixation between the tunica vaginalis and dartos within the scrotum. This event is more common before birth and, depending on the timing, may present as a nonpalpable “vanishing” testis in a child evalu-ated for cryptorchidism or as an abnormal scrotal testis on the first postnatal examination. Perinatal torsion may also occur within the first month of life, although partial degrees of extravaginal torsion are also reported as late as 9 months after birth. Rarely, cases of neonatal testicular infarction are attributable to necrosis without spermatic cord torsion or to intravaginal torsion (John et al, 2008).

The presentation of perinatal torsion is variable, depending on the timing of the torsion event, and may be insidious. Because of the rarity of the disease, most of the available data are based on small retrospective case series. As such, predisposing factors such as large birth weight and/or difficult delivery are postulated (John et al, 2008; Kaye et al, 2008a) but not confirmed in con-trolled studies. In a population-based study, John and coworkers (2008) estimated an incidence of 6.1 per 100,000 births, and famil-ial cases have been reported (Castilla et al, 1975). Suggestive

placement is offered after complete healing, usually 6 or more months later.

Prognosis. The long-term outcome of males with a history of testicular torsion is poorly defined because of difficulties inherent in completing follow-up studies, particularly for boys treated before puberty. Visser and Heyns (2003) collected data from avail-able clinical series and observed a stepwise decrease in testicular salvage and increase in late testicular atrophy with increasing duration of torsion. In their review of the testicular salvage rate in 1140 patients, the risk of orchiectomy was approximately 5%, 20%, 40%, 60%, 80%, and 90% at 0 to 6, 7 to 12, 13 to 18, 19 to 24, more than 24, and more than 48 hours after onset of pain, respectively. The approximate risk of late atrophy in 535 patients was less than 10%, 40%, and 75% after less than 12, 12 to 24, and more than 24 hours of pain, respectively, in those treated with orchidopexy. However, data from individual series suggest that at least partial (<25%) testicular atrophy is not rare in patients who underwent operative detorsion as little as 4 hours after onset of pain (Krarup, 1978; Anderson and Williamson, 1986; Tryfonas et al, 1994; Sessions et al, 2003). These data suggest that ischemic injury may occur rapidly, even if the testis appears viable at the time of detorsion. Even partial testicular volume loss may reflect significant loss of spermatogenesis in the testis (Turner et al, 2004), but the resultant impact on overall fertility potential is less clear. Available data suggest that subtle abnormalities of semen quality are common after testicular torsion: semen density is often in the normal range yet seems to show a positive correla-tion with shorter duration of torsion and reduced atrophy (Puri et al, 1985; Fisch et al, 1988; Anderson et al, 1992; Brasso et al, 1993; Arap et al, 2007). Unfortunately, these studies are small and heterogeneous, with limited semen analysis and minimal paternity data.

Sperm density is reduced in patients with testicular loss due to trauma relative to normal controls (Lin et al, 1998), but pater-nity in males with congenital monorchism appears to be normal (Lee and Coughlin, 2002b). In comparison, concern exists that fertility potential after torsion may be further reduced as com-pared with other males with a single testis because of bilateral testicular pathology in cases of unilateral torsion. As reviewed in Visser and Heyns (2003), existing contralateral testicular biopsy data are limited but suggest that global testicular dysfunction may exist in males with torsion. Whether this is a primary or second-ary defect, or both, remains undefined. The observation that increasing duration of torsion is inversely correlated with semen quality suggests an adverse effect of torsion itself. A hypothesis that this effect may be related to an autoimmune phenomenon (Anderson and Williamson, 1990) was not supported by analysis of antisperm antibodies in individuals with torsion (Puri et al, 1985; Anderson et al, 1992; Brasso et al, 1993; Arap et al, 2007). Animal models suggest a contralateral deleterious effect of torsion in some studies but not others, and the applicability of animal models for study of testis injury after torsion is controversial (Filho et al, 2004), but available animal and human data support a role for ischemia-reperfusion injury after release of testicular torsion (Kehinde et al, 2003; Turner et al, 2004). Additional clini-cal data are needed to determine long-term outcome after testicu-lar torsion and the efficacy of adjunctive treatment (e.g., antioxidant therapy) in optimizing fertility potential in patients with torsion.

Intermittent Intravaginal Spermatic Cord TorsionAs many as 30% to 50% of patients presenting with acute sper-matic cord torsion report a history of previous scrotal pain


may be possible when urgent or emergent surgery is performed (Sorensen et al, 2003; Al-Salem, 2007; Cuervo et al, 2007). In other reported cases, unexpected torsion or atrophy of the contralateral testis was found at the time of exploration at varying intervals after the ipsilateral diagnosis, indicating that the clinical signs of extravaginal torsion may indeed be subtle, delayed, and easily overlooked even by observant parents (Yerkes et al, 2005; Al-Salem, 2007; Baglaj and Carachi, 2007; John et al, 2008). Theoretical concerns regarding the anesthetic risks associated with urgent surgery for perinatal torsion are not confirmed by available data, but neonatal anesthesia expertise is recommended in these cases (Pinto et al, 1997; Sorensen et al, 2003; Yerkes et al, 2005). There-fore, to minimize loss of testicular tissue and the risk of anorchia, the most prudent approach is urgent explora-tion and contralateral orchidopexy once the diagnosis of perinatal torsion is made. To avoid the theoretical risk of transscrotal surgery in the event a tumor is found, some surgeons advocate an inguinal approach whereas others routinely use a scrotal incision. Retention of the testis is advisable if any chance of viability is present, particularly in postnatal or bilateral cases, to optimize the likelihood of retained endocrine function. As with other management controversies in urology, the pros and cons of alternative approaches to care should be discussed thoroughly with the patient’s family.

Appendage TorsionThe most common intrascrotal appendages are the appendix testis and appendix epididymis, remnants of the cranial müllerian and wolffian ducts, and present in 76% to 83% and 22% to 28% of testes, respectively (Dresner, 1973; Jacob and Barteczko, 2005). The vas aberrans and paradidymis, both appendages of wolffian duct origin, are rare (1% to 3% of patients). Appendage anatomy varies between individuals but includes sessile and pedunculated types; testicular appendices were more commonly sessile in a prenatal study (Jacob and Barteczko, 2005) but pedunculated in a postnatal torsion series (Jones, 1962). The appendix testis is located at the cranial testicular pole or in the groove between the testis and epididymis, and the appendix epididymis is located along the caput. The cause of torsion of an appendage is not known but may be related to anatomy, trauma, and/or prepubertal enlargement.

Appendage torsion is the most common cause of acute scrotum in prepubertal children. The peak age at occurrence is 7 to 12 years (mean 8 to 9 years) (Anderson and Giacomantonio, 1985; Mushtaq et al, 2003; Lyronis et al, 2009). Symptoms include sudden or gradual onset of testicular pain, which may be mild or severe and intermittent in some cases. Some series fail to show significant differences in the presenting complaints of boys with appendage as compared with testicular torsion, but, in general, patients with appendage torsion are less likely to present early in the course of symptoms or to have nausea and vomiting or generalized testicu-lar tenderness. In addition, pain may increase with activity and resolve at rest.

Physical findings depend on the severity of inflammation and duration of symptoms (Rakha et al, 2006). A blue dot sign was first described by Dresner (1973) as a discoloration seen through the scrotal wall in prepubertal boys when the skin is stretched over the upper pole of the testis early in the course of the disease. This sign is reportedly present in 0% to 52% of patients (Calda-mone et al, 1984; Van Glabeke et al, 1999; Karmazyn et al, 2005; Murphy et al, 2006; Lyronis et al, 2009) but was uncommon (10%) in one of the largest series of boys whose diagnoses were confirmed surgically (Makela et al, 2007). A single false-positive

clinical findings at birth include testicular induration and scrotal erythema or dark discoloration with or without edema. The infant is typically asymptomatic, and testicular tenderness may or may not be present. A hydrocele may coexist, complicating the testicu-lar examination. In a significant minority of cases, the symptoms present in the neonatal period or later, after documentation of a normal neonatal examination. Reports vary as to the frequency of bilateral versus unilateral perinatal torsion, with the former reported in 5% and 22% of cases in two large series (Yerkes et al, 2005; Baglaj and Carachi, 2007). Several recent series indicate that bilateral perinatal torsion is more common than suggested in the older literature and that asynchronous torsion may occur in boys in whom the primary event occurs prenatally or postnatally (Beasley and McBride, 2005; Yerkes et al, 2005; Al-Salem, 2007; John et al, 2008). In a review of the literature by Baglaj and Carachi (2007), asynchronous torsion comprised one third of all bilateral cases.

Although imaging of the testis may be obtained in cases of suspected perinatal torsion, its usefulness and reliability is ques-tionable. Maternal ultrasonography may show in-utero torsion as early as the 33rd week of gestation, and postnatally CDUS may reveal typical findings of parenchymal heterogeneity, calcification, and absent blood flow (Fig. 132–10) that are helpful in confirming the diagnosis of nonacute antenatal torsion (Arena et al, 2006). However, intact blood flow in cases of perinatal torsion is not uncommon, suggesting that postnatal CDUS may be unreliable (Yerkes et al, 2005; Al-Salem, 2007; Cuervo et al, 2007; John et al, 2008). Some advocate use of ultrasound to differentiate rare neo-natal testicular or peritesticular tumors from torsion (Kaye et al, 2008a), but its reliability in this regard may also be questionable (Calonge et al, 2004; Al-Salem, 2007). Therefore, clinical findings usually provide the basis for diagnosis of perinatal torsion, particu-larly because imaging may delay treatment and many clinicians now advocate urgent surgical exploration.

The treatment of perinatal testicular torsion remains controver-sial. Some surgeons support the view that exploration and contra-lateral orchidopexy is best performed electively in cases of perinatal torsion because most cases occur prenatally and are not salvage-able (Das and Singer, 1990; Brandt et al, 1992; Stone et al, 1995; Kaye et al, 2008a). However, partial or complete testicular salvage

Figure 132–10. Extravaginal spermatic cord torsion. Transverse ultrasound image shows both testes in a neonate with left prenatal torsion. Note enlarged testis with heterogeneous parenchyma and bilateral hydroceles.


defined and controversial (Lau et al, 1997; Merlini et al, 1998; Cappele et al, 2000; Somekh et al, 2004; Al-Taheini et al, 2008; Sakellaris and Charissis, 2008). Nonoperative series suggest a higher prevalence (40% to 60%) than that reported for operative series (5% to 15%), probably owing to difficulty differentiating epididymitis from appendix testis torsion clinically (Kadish and Bolte, 1998; Lam et al, 2005; Lyronis et al, 2009). In many series peaks in prevalence occur in infancy and at puberty (Sidler et al, 1997; Mushtaq et al, 2003; Makela et al, 2007). Symptoms are similar to those reported for other causes of acute scrotal pain but may be more gradual in onset. Nausea and vomiting are extremely rare, but fever or voiding symptoms may be present. Localized epididymal enlargement and tenderness are present, and the cremasteric reflex is symmetric. CDUS shows increased epididymal size and blood flow (Fig. 132–12) as well as increased testicular flow in some cases; however, it is important to note that these same physical and imaging findings may be associated with inter-mittent testicular or appendix testis torsion. Associated pyuria and/or bacteriuria are reported in 20% to 40% of cases that were confirmed intraoperatively (Anderson and Giacomantonio, 1985; Sidler et al, 1997; Mushtaq et al, 2003; Murphy et al, 2006; Makela et al, 2007). Known risk factors for both urinary tract infection and epididymitis include neurogenic and non-neurogenic voiding dysfunction; clean intermittent catheterization (CIC); urethral abnormalities including hypospadias, urethrorectal fistula, and stricture (Karmazyn et al, 2009); and congenital anomalies of the ejaculatory duct (see Fig. 132–12) (Pimpalwar et al, 2002; Yanai et al, 2005). Boys with anomalies are more likely to have severe inflammation of the epididymis and recurrent episodes (Karmazyn et al, 2009). Noninfectious epididymitis is attributed to milder forms of bladder dysfunction, unusual bacterial or viral infections, or trauma, but conclusive evidence supporting these causes is unavailable (Bukowski et al, 1995a; Somekh et al, 2004). Sexually transmitted disease is the most likely cause in postpubertal sexu-ally active males.

Because the historical, physical, and imaging findings are non-specific and the disease is rare in prepubertal children, some clini-cians diagnose epididymitis only when signs of infection are present. Al-Taheini and coworkers have proposed strict criteria for diagnosis that include acute scrotal pain and epididymal hyper-emia on CDUS in addition to at least two of the following: fever

case of a blue dot sign in a patient with testicular torsion has been reported (Murphy et al, 2006). Other associated early signs supportive of the diagnosis include a tender nodule superior to the testis with limited testicular tenderness, a symmetrical (present or absent) cremasteric reflex, and intact epididymal land-marks. However, with longer duration there may be increasing difficulty in differentiating appendage torsion from other causes of acute scrotum, because many of the symptoms are nonspecific and the scrotal examination may show increasing testicular enlargement and tenderness and marked scrotal swelling and erythema. These secondary signs may progress even in the absence of worsening pain and contribute to prolonged resolu-tion. In a large series of 840 boys with scrotal pain, 5% required reexploration for metachronous contralateral appendiceal torsion (Ben-Meir et al, 2006).

CDUS in cases of appendage torsion is operator dependent and may show hyperperfusion of the epididymis with or without an enlarged (typically > 5 mm) appendix testis or may appear normal (Baldisserotto et al, 2005). When visible by CDUS, the normal appendix testis contains no internal blood flow and has a mean diameter of 3.1 ± 0.8 mm (Yang et al, 2005) whereas the twisted appendage may appear as an ovoid hyperechoic, hypoechoic, or heterogeneous nodule without blood flow (Fig. 132–11). When visible this finding is helpful, but its absence does not rule out appendage torsion. Similarly, epididymal hyperemia may indicate epididymitis or testicular detorsion.

The high prevalence of appendiceal torsion and long-recognized expectation of spontaneous resolution with conservative management supports nonsurgical management of the majority of patients, particularly in boys in whom the diagnosis is clear (Koff and De Ridder, 1976). In most cases symptoms resolve spon-taneously with strict limitation of activities until pain resolves and use of a nonsteroidal anti-inflammatory agent such as ibuprofen. In some cases pain and swelling is exacerbated by athletic activities. Rarely, prolonged and severe pain or recurrent episodes warrant surgical excision of the appendage to reduce pain and morbidity.

EpididymitisIn children, the true incidence and cause of infectious or noninfec-tious inflammation of the epididymis, or epididymitis, is poorly

Figure 132–11. Torsion of a testicular appendage. CDUS shows (A) a heterogeneous enlarged appendix of 7 mm in greatest diameter and (B) increased flow to testis and epididymis and avascular appendix. The patient was treated conservatively, and the examination findings normalized within 1 week.

A B


or bilateral scrotal redness and swelling with or without pain (Klin et al, 2002; Lee et al, 2009). Associated findings may include local spread of erythema or edema to the inguinal or perineal region, inguinal lymphadenopathy, leukocytosis, and/or eosino-philia, the latter suggesting an allergic cause although the etiology is most likely multifactorial. Distinctive characteristics include minimal or no pain, scrotal but not testicular tenderness, and thickening of the scrotal wall by ultrasonography. Treatment is observation and possible use of antihistamines with resolution expected over several days. Henoch-Schönlein purpura is a form of acute vasculitis affecting the skin, joints, gastrointestinal tract, and kidneys that presents as scrotal findings in 2% to 38% of cases and may include edema or erythema; testicular hematoma, torsion or infarction; or cord thrombosis or epididymitis (Turkish et al, 1976; Diana et al, 2000; Ioannides and Turnock, 2001). A typical purpuric rash of the buttocks, perineum, and lower limbs is usually present but may not precede the scrotal findings. Urgent scrotal exploration is indicated if clinical findings suggest con-comitant testicular torsion. Cystic dysplasia of the rete testis may present as acute scrotal swelling and pain (Noh et al, 1999; Smith et al, 2008; Jeyaratnam and Bakalinova, 2010). Rarely, an associ-ated ureteral anomaly may lead to chronic testicular pain (McGee et al, 2009). Cystic dysplasia is associated with ipsilateral renal dysplasia, agenesis, or ureteral anomalies in the majority of cases and likely represents a failure of normal wolffian duct develop-ment. The diagnosis is confirmed by ultrasonography, which shows multiple small centrally located cysts within the testis. Treatment is conservative enucleation, which may be associated with recurrence, or observation, which is associated with regres-sion in some cases.

EPIDIDYMAL, VASAL, AND SCROTAL ANOMALIESCongenital anomalies of accessory testicular structures are often associated with primary diseases affecting testicular descent and genital development but may occur as isolated anomalies or as part of syndromes that do not primarily affect the genitalia.

Epididymal cysts are anechoic simple cystic structures that may be palpable by the patient or examining physician or found incidentally by ultrasonography (Homayoon et al, 2004). These

greater than or equal to 37.5° C, leukocytosis, pyuria (>10 white blood cells per high-powered field), and/or positive urine culture (Al-Taheini et al, 2008). Using these criteria they identified 16 patients with epididymitis; of these 10 had a documented urinary tract infection, 15 had a normal renal ultrasound study, and 1 of 13, a boy with a history of imperforate anus, had an abnormal voiding cystourethrogram. Other clinical series document a low risk of urinary tract anomalies in boys with epididymitis, although infants may be at higher risk (Merlini et al, 1998; Sakellaris and Charissis, 2008). However, anomalies such as pyelectasis, low-grade vesicoureteral reflux, and renal duplication that comprise the majority of findings may be incidental whereas direct contrib-uting factors such as urethral or ureteral obstruction, ejaculatory duct, or vasal anomalies are rare.

In the absence of urinary tract infection, symptoms improve spontaneously without antibiotic therapy (Lau et al, 1997) and the need for urinary tract imaging in otherwise normal boys remains controversial. Recommendations include renal ultrasonography only (Al-Taheini et al, 2008) or no imaging unless the problem is recurrent (Cappele et al, 2000). In cases of documented urinary tract infection associated with epididymitis or progression to epididymo-orchitis, aggressive treatment including intravenous antibiotics and hospitalization may be necessary and imaging workup of the urinary tract, including renal ultrasonography and voiding cystourethrography, is indicated after resolution of the infection. In recurrent cases, endoscopy may reveal ejaculatory duct abnormalities that are not evident on voiding cystourethrog-raphy (Pimpalwar et al, 2002; Yanai et al, 2005). Recurrent epididymo-orchitis in these cases may require excision of a utricle or ejaculatory duct cyst with vasovasostomy or vasectomy.

Other Causes of Acute Scrotal PainA large number of conditions affecting the scrotum or intrascrotal contents may present as scrotal pain and/or swelling (see Table 132–6). Trauma, although not uncommonly reported in boys with testicular or appendage torsion, may also lead to acute scrotal swelling and pain in cases of hematocele due to testicular rupture or to intra-abdominal injury in the presence of a communicating hydrocele. CDUS appears to be sensitive in diagnosing testicular fracture in adolescents, and surgical intervention is indicated (Adams et al, 2008). Boys with idiopathic scrotal edema are typi-cally prepubertal (2 to 12 years old) and present with unilateral

Figure 132–12. Epididymitis with utricle and seminal vesicle reflux in a male 3-month-old with trisomy 21, micropenis, and Escherichia coli urinary tract infection. A, Color Doppler ultrasonography shows an enlarged, hyperemic, and heterogeneous right epididymis; B, Voiding cystourethrography shows reflux into the right ejaculatory duct and seminal vesicle.

A B


hypospadias, tracheoesophageal fistula, tetralogy of Fallot, or coarctation of the aorta.

Scrotal anomalies including ectopic scrotum and penoscro-tal transposition are rare but frequently occur in association with other congenital anomalies (Parida et al, 1995; Hoar et al, 1998). An ectopic scrotum may be suprainguinal, inguinal/femoral, or perineal (accessory). The suprainguinal form is unilat-eral, associated with an ectopic intrascrotal or cryptorchid testis, and often associated with ipsilateral renal anomalies. The femoral ectopic scrotum may be unilateral or bilateral and is associated with lip, palate, and limb anomalies, whereas the perineal (acces-sory) scrotum is commonly associated with a perineal lipoma (Park and Hong, 2006). Similarly, penoscrotal transposition occurs in severe hypospadias (Pinke et al, 2001) but is also associated with multisystem renal, CNS, vertebral, limb, and/or cardiac defects (Parida et al, 1995). Perineal lipomas may occur in association with a spectrum of scrotal anomalies, suggesting that they repre-sent a cause or consequence of abnormal development of the labioscrotal folds (Park and Hong, 2006).

Please visit the accompanying website at www.expertconsult.com to view videos associated with this chapter.

SUGGESTED READINGSEmbryology of Testicular Development and DescentAdham IM, Agoulnik AI. Insulin-like 3 signalling in testicular descent. Int

J Androl 2004;27:257–65.Barteczko KJ, Jacob MI. The testicular descent in human: origin, develop-

ment and fate of the gubernaculum Hunteri, processus vaginalis perito-nei, and gonadal ligaments. Adv Anat Embryol Cell Biol 2000;156:III–X, 1–98.

Cool J, Capel B. Mixed signals: development of the testis. Semin Reprod Med 2009;27:5–13.

CryptorchidismBaker LA, Docimo SG, Surer I, et al. A multi-institutional analysis of lapa-

roscopic orchidopexy. BJU Int 2001;87:484–9.Barthold JS, Gonzalez R. The epidemiology of congenital cryp-

torchidism, testicular ascent and orchiopexy. J Urol 2003;170:2396– 401.

Cendron M, Huff DS, Keating MA, et al. Anatomical, morphological and volumetric analysis: a review of 759 cases of testicular maldescent. J Urol 1993;149:570–3.

Cortes D. Cryptorchidism—aspects of pathogenesis, histology and treat-ment. Scand J Urol Nephrol Suppl 1998;196:1–54.

Foresta C, Zuccarello D, Garolla A, Ferlin A. Role of hormones, genes, and environment in human cryptorchidism. Endocr Rev 2008;29:560–80.

Wood HM, Elder JS. Cryptorchidism and testicular cancer: separating fact from fiction. J Urol 2009;181:452–61.

VaricoceleBarroso U Jr, Andrade DM, Novaes H, et al. Surgical treatment of varicocele

in children with open and laparoscopic Palomo technique: a systematic review of the literature. J Urol 2009;181:2724–8.

Gargollo PC, Diamond DA. Current management of the adolescent varico-cele. Curr Urol Rep 2009;10:144–52.

Kolon TF, Clement MR, Cartwright L, et al. Transient asynchronous testicu-lar growth in adolescent males with a varicocele. J Urol 2008;180: 1111–14.

Laven JS, Haans LC, Mali WP, et al. Effects of varicocele treatment in ado-lescents: a randomized study. Fertil Steril 1992;58:756–62.

Hernia/Hydrocele and Acute ScrotumBaglaj M, Carachi R. Neonatal bilateral testicular torsion: a plea for emer-

gency exploration. J Urol 2007;177:2296–9.Brandt ML. Pediatric hernias. Surg Clin North Am 2008;88:27–43.Cozzi DA, Mele E, Ceccanti S, et al. Infantile abdominoscrotal hydrocele:

a not so benign condition. J Urol 2008;180:2611–15; discussion 2615.

may be clinically indistinguishable from spermatoceles except that the latter occur postpubertally and contain sperm. The patho-physiology of epididymal cysts is unknown but may be related to an altered hormonal environment because they are linked to DES exposure (Palmer et al, 2009). These lesions are different ultraso-nographically and pathologically from the multicystic/solid epi-didymal cystadenomas that occur in von Hippel-Lindau disease (Choyke et al, 1997). Homayoon and associates (2004) observed spontaneous resolution of many cysts observed in their pediatric series, and surgical intervention is rarely needed.

Congenital absence of the vas deferens (CAVD) is in most cases associated with specific mutations of the cystic fibrosis gene CTFR (cystic fibrosis transmembrane regulator) that are less severe than those encountered in patients with cystic fibrosis (McCallum et al, 2001; Kolettis and Sandlow, 2002). The disease can be bilat-eral (CBAVD) or unilateral (CUAVD) with a normal or obstructed contralateral vas and may be associated with renal agenesis or ectopia and/or partial or complete agenesis of the epididymis and seminal vesicles. CTFR mutations are more common in males with CBAVD, and renal anomalies are more common in cases of CUAVD. These patients typically present with infertility. Abnormal vasal development may also result in a persistent mesonephric duct anomaly that is associated with ipsilateral renal and seminal vesicle agenesis and vasoureteral fusion (Kajbafzadeh and Payabvash, 2006). Reflux into the fused wolffian remnants results in urinary tract infection and epididymo-orchitis. Other associated anomalies may include imperforate anus,

Key Points: Hernia/Hydrocele and Acute Scrotum

● Routine contralateral exploration in cases of unilateral inguinal hernia is not recommended.

● Noncommunicating scrotal hydroceles are more common in neonates and adolescents; the rare abdominoscrotal variant occurs primarily in infancy and requires repair.

● Diagnoses in cases of acute scrotum include appendix testis torsion (40% to 60%), spermatic cord torsion (20% to 30%), epididymitis (5% to 15%) and other or no pathol-ogy (10%).

● The anatomic abnormality predisposing to torsion of the spermatic cord is the bell-clapper deformity and occurs in about 12% of males.

● Findings most suggestive of spermatic cord torsion include puberty, absent cremasteric reflex, short duration (<6 hours) of pain, and reduced or absent blood flow and/or a visible spermatic cord twist on ultrasound imaging.

● Findings most suggestive of appendix testis torsion include prepuberty, a localized tender nodule at the superior testis pole, a blue dot sign, and a preserved cremasteric reflex.

● When findings support or are suggestive of spermatic cord torsion, emergent scrotal exploration is indicated and should not be delayed for diagnostic testing.

● Intrascrotal fixation of the testis must be performed bilater-ally because a contralateral bell-clapper deformity usually exists and may lead to metachronous torsion.

● Epididymitis associated with urinary tract infection or with recurrent episodes warrants urinary tract evaluation with imaging to rule out urethral or ureteral anomalies.

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Eaton SH, Cendron MA, Estrada CR, et al. Intermittent testicular torsion: diagnostic features and management outcomes. J Urol 2005;174:1532–5; discussion 1535.

Mansbach JM, Forbes P, Peters C. Testicular torsion and risk factors for orchiectomy. Arch Pediatr Adolesc Med 2005;159:1167–71.

Ron O, Eaton S, Pierro A. Systematic review of the risk of developing a metachronous contralateral inguinal hernia in children. Br J Surg 2007;94:804–11.

Sessions AE, Rabinowitz R, Hulbert WC, et al. Testicular torsion: direction, degree, duration and disinformation. J Urol 2003;169: 663–5.

Visser AJ, Heyns CF. Testicular function after torsion of the spermatic cord. BJU Int 2003;92:200–3.

REFERENCES The complete reference list is available online at www.expertconsult.com.
