- Email: [email protected]
Testicular Undescent and Torsion
Management Principles in Pediatric Urology
0031-3955/87 $0.00
+ .20
Testicular Undescent and Torsion
Eric W. Fonkalsrud, MD*
EMBRYOLOGY The embryonic development of the testis may be divided into three phases: intra-abdominal (1-7 months), canalicular (7-8 months), and scrotal (8--9 months). As the anterior abdominal wall develops, the gonad becomes attached at the site of the future inguinal canal by fibers of the developing gubernaculum. 1 The contractile muscle fibers of the gubernaculum are believed to cause the testicle to migrate through the inguinal canal in the seventh fetal month. The gubernaculum is attached superiorly to the proximal tip of the vas deferens and is believed to divided distally into several tails extending to the dartos muscle in the scrotum, Colles' fascia in the perineum, the pubic tubercle and crest, the inguinal ligament and the fascia lata in the femoral triangle. 2 Although the testicle normally follows the course of the scrotal extension, occasionally it may follow one of the other gubernacular tails to an ectopic location in the perineal, suprapubic, or femoral areas. The descent of the testis is attributed to the three combined forces of intraabdominal pressure, intramuscular pressure due to the contraction of the muscles draped around the canal, and the guidance and active contraction of the gubernaculum. 3 The testis and gubernaculum are covered by peritoneum before the descent begins along the inguinal canal, dorsal to the peritoneal cavity. Before and during descent, the testis and spermatic cord enlarge and the vessels of the cord lengthen and become tortuous, increasing the mobility of the testis. The testis then progresses through the inguinal canal and descends into the scrotum. The testis carries with it an extension of the peritoneal cavity, the processus vaginalis. Later, the testis becomes covered by a reflected fold of the processus, although it lies entirely outside the peritoneal cavity. After the gonad reaches the scrotum, the gubernaculum becomes indistinct as an identifiable structure. Many aspects of the embryologic and morphologic development of the testicle remain undefined. *Professor and Chief of Pediatric Surgery, UCLA School of Medicine, Los Angeles, California From the Department of Surgery, UCLA School of Medicine, Los Angeles, California
Pediatric Clinics of North America-Vol. 34, No.5, October 1987
1305
1306
ERIC
W.
FONKALSRUD
HORMONAL INFLUENCES The Sertoli cells of the testis produce a locally active substance (mullerianinhibiting substance) responsible for regression of the paramesonephric (mullerian) duct. 4 The Leydig cells produce locally acting testosterone responsible for differentiating the mesonephric duct into wolffian structures. S Testicular secretion of testosterone into the general circulation and its peripheral conversion to dihydrotestosterone is responsible for masculinizing the external genitalia. 6 Defects in any of these testicular functions can result in conditions such as male pseudohermaphroditism, with or without cryptorchidism. Zondek7 and Aschheim 8 describe the presence of gonad-stimulating hormones in the urine of pregnant women that was different from that found in urine from postmenopausal women. Jost9 showed that a sufficiently large amount of circulating male hormone in the fetus may cause testicular descent. Zondek7 noted that high levels of gonadotropic hormones are present in the human maternal circulation until the third trimester, when they begin to drop. Nelson lO demonstrated that maternal gonadotropic hormones stimulate production of androgenic hormones from the fetal testis. High levels of gonadotropin are present in the circulation during the last eight weeks of fetal development, and then are almost absent from birth until about 10 to 12 years of age, when the levels rise again. 11 Testicular descent is believed to be greatly influenced by the presence of these demonstrable hormones during fetal development; however, there is no clear evidence that true cryptorchid testes with mechanical obstruction will descend further in response to exogenous or endogenous hormones after the first three months of life. 12.13 Failure of the testicle to descend during the third trimester may be related either to the inadequacy of the hormones, or more likely to the failure of the testis to respond to them, since over 75 per cent of undescended testes are unilateral. Normal testicular volume is less than 2 ml up to the age of 11 years. At age 12 years, the volume ranges from 2 to 5 ml; at age 13 years from 5 to 10 ml and at 15 years from 12 to 14 ml. 14
TYPES OF UNDESCENDED TESTES Retractile Testes An extensive study of human inguinal anatomy by Browne lS indicated that more than three fourths of the testes not located in the scrotum of children were held in higher pOSition by an "overactive" cremaster muscle. Retractile testes are believed to ascend from the scrotum because of an overactive cremaster muscle and failure of complete attachment of the lower pole of the testicle to the scrotum by the gubernaculum. By this normal muscular action, the testes are held high spontaneously during periods of stimulation. Such testes usually descend into the scrotum spontaneously when the child is asleep or relaxes, as in a warm bath. Retractile testes are usually bilateral, in contrast to true undescended testes. At puberty the testicle becomes larger than the external ring, the cremaster muscle becomes less active, and the retractile testis usually remains in the scrotum. If at any time the testis can be manipulated into the low scrotum, the patient has a retractile testis and parents can be reassured that the testis will eventually reside in the normal scrotal position, usually well before puberty. Testicular volume and function in retractile testicles are believed to be normal in adulthood. 16
TESTICULAR UNDESCENT AND TORSION
1307
Ectopic Testes The true cryptorchid testis should be distinguished from an ectopic testis that has progressed normally through the inguinal canal and emerged from the external ring but has been directed away from the scrotum into the thigh, the suprapubic area, or the perineum. Transverse ectopia to the contralateral groin has been reported. The rarity of true ectopia is evidenced by the fact that in a review of more than 153 male infants with testicular undescent, Scorer'7 found no infants with true ectopia. Approximately 80 per cent of ectopic testes are unilateral, usually normal in size, with normal spermatogenic and androgenic function. Regardless of location, they should be placed into the scrotum surgically. Attempts to move ectopic testes into the scrotum with hormone therapy have been ineffective. 18
Anorchia Normal male (wolffian) ductal development depends on fetal androgenic stimulation from the differentiated testis. With the complete absence of testicular tissue, female (miillerian) ductal development differentiates into the feminine configuration. Rarely, one testis may fail to develop, more commonly on the right and occasionally associated with ipsilateral agenesis of the kidney and ureter. The vas deferens in these patients is usually hypoplastic and ends blindly at the internal inguinal ring. The ipsilateral scrotum is often underdeveloped. Anorchia has been reported to occur in from 3.3 per cent to 5.2 per cent of boys operated on for cryptorchidism. '8 , 19 Anorchia is unilateral in approximately 85 per cent of cases. The surgeon should be encouraged to seek a nonpalpable, high undescended testis, inasmuch as total absence is uncommon. On rare occasions no viable testicular tissue on either side is evident, although the external genitalia are fully differentiated in masculine configuration at birth and a vestigial vas deferens terminates blindly in the abdomen. Torsion or obstruction to testicular blood supply is believed to play a role in this "vanishing testis" syndrome. Puberty is delayed, characterized by persistent elevations of plasma FSH and LH levels and low plasma testosterone levels. Although abdominal ultrasound and computer-assisted tomography (CT) may be of some help in identifying intra-abdominal testes, surgical exploration is necessary to establish the diagnosis. Exogenously administered testosterone in early adolescence produces a gratifying response of male sexual maturation. Testicular prostheses can be inserted after testosterone therapy has enlarged the scrotum.
Undescended Testes It is generally recognized that the undescended testis that does not descend into the scrotum spontaneously, with hormone therapy or with operation, by the fourth year of life probably will not achieve normal spermatogenic function in adolescence. It is further recognized that the higher the testis resides above the scrotum, the more dysgenetic the morphologic features of the gonad are likely to be. Most cryptorchid testes are prevented from reaching the scrotum because the spermatic artery is shorter than normal. It is not known whether blood flow in the spermatic artery of the undescended testis is less than that in the normal descended gonad. Inasmuch as more than 75 per cent of true undescended testes occur unilaterally, a specific hormonal deficiency that might account for the cryptorchidism has been difficult to identify. Children with bilateral cryptorchidism are more likely to have an endocrinologic disturbance with hormonal deficiency than are those with unilateral undescent; they also tend to have anatomic disturbances limiting descent of the testes (e.g., exstrophy of the bladder, gastroschisis, prune belly syndrome and a variety of other disorders). Approximately 8 per cent of undescended testes are primarily dysgenetic,
1308
ERIC
W.
FONKALSRUD
AGE DISTRIBUTION OF SPERMATOGONIA IN DESCENDED AND UNDESCENDED TESTICLES w
S
1000
[J Descended
In
:::>
•
I-
Undescended
~ Z W
IZ
150
o U Z
50 30 20
~
10
oC) o ~
c:::
W 0..
(/)
o
~
2
3 4
5 6 7 8 9 10 11 AGE IN YEARS
12 13 15
Figure 1. Average spermatogonia counts per tubule (average of 50 tubules counted) obtained from 237 unilaterally descended testes and from 515 unilaterally undescended testes revealed by biopsies taken from children up to the age of 15 years. The striped area shows the normal range of spermatogonia counts of bilaterally descended testes. [J Descended, • undescended. (From Mengel W, Zimmermann FA, Hecker W: The Undescended Testes. Chicago, Year Book Medical, 1981; with permission.)
usually high in location, and will never experience adequate spermatogenic function despite any form of therapy. Nonetheless, most undescended testes that have interstitial tissue and Leydig cells will produce sufficient testosterone to cause virilization. The incidence of true undescent ranges from 20 to 30 per cent in premature infants and from 1.8 to 4.0 per cent in mature newborn infants. Subsequent descent within the first 9 months of life occurs in most infants with originally undescended testes. '1 After the first year of life, true undescent is pathologic, occurring in approximately 0.7 per cent at that age. Contrary to previous views, it has been shown by examination of testicular weight, diameter of seminiferous tubules and spermatogonia counts that the young child's gonads have a linear development pattern before puberty. 20 Damaging influences causing morphologic changes in the undescended testis begin by the end of the second year. 21 Considerable controversy has existed regarding the age at which damage to a dystopic testis begins. Using the spermatogonia count as well as qualitative examination of the ultrastructure of interstitial tissue, Mengel et al. was able to show several significant features in 578 malpositioned" testes. 21 In almost all cases, the undescended testis showed no histomorphologic changes during the first two years of life. The mean values of spermatogonia counts were in the normal range; however, after the second year, the spermatogonia counts decreased significantly. The spermatogonia counts in these patients were within the range of 10, indicating that they remained low until puberty (lower limit for normal is 30; Fig. 1). In 1974, Redinger evaluated 619 testicular biopsies from 450 boys with unilateral and bilateral cryptorchidism between the ages of 2 months and 10 years, 22 noting that the mean spermatogonia counts dUring the first year of life were equal to those found in normally descended testes. A difference in the spermatogonia
TESTICULAR UNDESCENT AND TORSION
1309
counts between normal and cryptorchid testes was observed during the second and third year, but after the third year, the mean spermatogonia values from cryptorchid testes were significantly lower than normal and remained at the same level until the beginning of puberty. There was no difference in the spermatogonia counts between unilateral and bilateral cryptorchid testes of the same type. It was suggested by this author that a reduced number of spermatogonia may be acquired during the early stages of development, although he never found complete absence of spermatogonia. Electron microscopic examination of testicular connective tissue shows that with increasing age, the undescended testis tends to degenerate, leading to interstitial enlargement and fibrosis. There is no difference in extent of interstitial tissue and in ultrastructural appearance between an undescended and a descended testis during the first year of life. After the fourth year, however, increasing fibrosis appears with interstitial tissue of the undescended testis enlarged compared to that of bilateral descended testes.21 Early ultrastructural morphologic changes in cryptorchid testes have been demonstrated in the second and third years of life.23, 24 It remains unclear whether the underlying mechanism is a primary diminution of spermatogonia accompanied by atrophy of the tubules with secondary thickening and fibrosis, or an atrophy of the germinal epithelium owing to diminished vascularization caused by primary expansion of the connective tissue. It has long been of clinical interest that not only the dystopic but also the contralateral descended testis shows abnormal morphologic changes during the early years of childhood. Several authors 25 , 26 have found damage in the germinal epithelium of the orthotopic testis in 30 to 50 per cent of cases of contralateral undescent. Hasli observed such a marked decrease in spermatogonia counts in every sixth patient with unilateral undescent that subsequent infertility could be predicted. 27 Using a morphometric test, Staedtler showed that the spermatogonia count is lowered in both orthotopic and dystopic testes compared with controls. 28 Histological examination of 262 biopsies from unilaterally descended testes in patients with contralateral undescent showed an abnormal germinal epithelium in 61 per cent (Fig. 2). Mengel et al. confirmed previous observations that the spermatogonia counts from unilaterally descended testes are considerably higher than those from unilaterally undescended testes, but they have been lower than mean values from normal controls. 21 It has been our experience that the spermatogonia counts and fertility of patients with very low-lying testes are far superior to those in patients who have higher-lying testes, regardless of the form of treatment. Experimental studies in dogs reported by several authors indicate that experimental malposition of one testis induces pathomorphologic changes in the contralateral descended testis as measured by lower spermatogonia counts. 29, 30 The presence of autoantibodies against spermatozoa has been recognized for many years and demonstrated in large series of patients who have various testicular disorders. 31 Murthy et al. demonstrated circulating antibodies against basement membrane of the tubular wall as well as against the germinal cells in a patient with multiple endocrinologic disorders.32 Haensch found a close correlation between the presence of autoantibodies against spermatozoa and conditions causing testicular dystopia. 33 According to the results of Johnson34 and Tung et al. 35, 36 the basement membrane of the seminiferous tubules acts as a immunologic barrier that under normal circumstances keeps antibodies from penetrating into the seminiferous tubules. Under pathologic conditions, the basement membrane may become porous and several parts of the seminiferous tubules may be exposed to antibodies, possibly leading to an antigen-antibody reaction. Azathioprine has improved the spermatogonia counts in both dystopic and orthotopic testes of experimentally cryptorchid dogs. 31
1310
ERIC
W.
FONKALSRUD
SPERMATOGONIA COUNTS Unilaterally Orthotopic (262 biopsies)
Un i1atera lIy Dystopic (262 biopsies)
(From Mengel et ai, 1981)
Figure 2. Spermatogonia counts from biopsies obtained from 262 children with unilaterally undescended testes (50 tubules counted per biopsy). Whereas 84 per cent of undescended testes had spermatogonia counts of less than 30 per tubule (abnormal), 62 per cent of the contralateral descended testes had abnormal spermatogonia counts. (From Mengel W, Zimmermann FA, Hecker W: The Undescended Testes. Chicago, Year Book Medical, 1981; with permission.)
Kiesewetter et al. 37 as well as others38• 39 have demonstrated that young children who undergo orchiopexy subsequently show an increase in the spermatogonia count. This observation is verified in the experimental dog with unilateral cryptorchidism in which a significant increase in spermatogonia count can be demonstrated after scrotal orchiopexy.
TREATMENT The primary criterion for determining the successful treatment of cryptorchidism and the optimal date for initiating therapy is delayed fertility, not merely the presence of a palpable testis in the scrotum. It is difficult to compare the results among patients who have undergone different types of fertility studies after orchiopexy, but it is apparent that published fertility results up to 10 years ago have in general been unsatisfactory. The main reason for the .eported low fertility rates is that nearly all of the patients received no treatment until after the age of 6 years. In our series of over 200 patients operated on before the age of 5 years, the sperm count exceeded 20 million per ml in over three fourths of patients with unilateral undescent who did not have atrophic or absent testes. Human chorionic gonadotropin (HCG) therapy produced descent only in testes considered retractile or high scrotal, and almost all resumed the elevated position 1 month after therapy. Following completion of a course of therapy including 10,000 units of HCG over a 2-week period, only patients with testes located in these positions responded with descent into the scrotum. A course of HCG prior to orchiopexy enlarges the testis
TESTICULAR UNDESCENT AND TORSION
1311
Figure 3. A, Lengthy course of the spermatic artery descending from the aorta through the internal inguinal ring to the undescended testis in the inguinal canal. B, By transposing the internal inguinal ring medially to the pubis, the course of the spermatic artery may be lengthened effectively to permit the testis to be placed into the scrotum, the basis of the standard orchiopexy. (From Fonkalsrud EW: Curr Probl Surg 15:35--47, 1978; with permission.)
and the spermatic vessels, making the technical repair easier. The policy recommended by Mengel et al. to operate on children only if descent is not induced by a course of HCG before the age of 2 years has considerable merit. 21 The major problem in our experience is the unwillingness of the family to have the child receive a series of intramuscular injections before operation when the likelihood of HCG producing descent is less than 10 per cent. The fertility rate reported by Knorr after HCG therapy is 46 per cent and is increased after orchiopexy by another 25 per cent. Although the experience with LHRH in causing descent has had limited trial in the United States, preliminary studies indicate that the results have been no better than with the use of HCG. Nonetheless, studies by Hadziselimovic41 have strongly suggested that LHRH produces descent in most patients with an empty scrotum on whom the agent is used. Double-blind control studies by Rajfer et al. and others have failed to show improvement in producing descent with the use of LHRH.42
Surgical Treatment Current evidence suggests that the optimal time for performing orchiopexy is before the age of 4 and probably as early as 2 years. The technique of orchiopexy currently in general use has been described and illustrated by several authors. 43 The objective of the repair is to alter the course of the spermatic artery from the renal pedicle, through the internal inguinal ring, to the external inguinal ring, and to create in its place a direct line from the renal pedicle to the scrotum (Fig. 3). A small incision is made through the lowermost abdominal skin crease, and the external oblique aponeurosis is opened in the direction of its fibers through the external ring. The testicle usually is found protruding through the external ring
1312
ERIC W. FONKALSRUD
inferior to the internal oblique muscle with attachments to the pubis. The testis with its surrounding tunica vaginalis is mobilized from the gubernaculum and often tenacious surrounding attachments, permitting it to be elevated with gentle traction. The cremaster muscle is mobilized gently from the spermatic vessels and the vas deferens up to the level of the internal inguinal ring. The internal oblique muscle is divided lateral to the internal ring for approximately 1 cm to obtain better exposure. The inferior epigastric artery and veins are divided and the transversalis fascia is opened widely through the internal ring to permit wide exposure of the retroperitoneal space. The accompanying hernia sac, which is present in approximately 90 per cent of patients, is separated from the spermatic vessels and the vas, often a delicate maneuver because the structures are tenaciously adherent and the sac tears easily. The maneuver can be facilitated by injecting a small amount of saline through a small-gauge needle between the hernia sac and the cord structures and then gently developing a plane by blunt dissection with a fine clamp. High ligation of the hernia sac is performed with a fine transfixion suture. The gonad is inspected to note its size, consistency, and any abnormal features. Biopsy is not recommended routinely because of the risk of further injury to the delicate organ, especially in the young child, unless any unusual features are apparent, or if the child is older than 12 years. A thin wedge biopsy running longitudinally on the side opposite the epididymis is preferred, closing the wound with fine continuous suture. The testicle is placed into the tunica, the proximal end of which is closed loosely to prevent dislodgment outside the sac. The dissection is continued into the retroperitoneal space by elevating the peritoneum, sharply dividing the lateral spermatic fascia, and bluntly mobilizing the spermatic vessels up to the lower pole of the kidney and the vas over to the bladder. The scrotum is forcibly stretched by inserting a finger through the wound to the lowermost portion of the sac. A small incision is made through the scrotal skin at this point and a space sufficiently large to accommodate the testis is developed between the dartos muscle and the scrotal skin by blunt dissection. A small opening is then placed in the dartos fascia and muscle layer, through which a clamp is passed superiorly to direct the testicle downward to the scrotum. Twisting the spermatic vessels must be avoided. The upper edge of the tunica is stitched to the dartos layer circumferentially to prevent upward displacement or subsequent torsion, and the testis placed subcutaneously. The scrotal skin is closed loosely with fine absorbable sutures. The transversalis fascia is then closed with nonabsorbable sutures, leaving a small opening just lateral to the pubis to function as the new internal inguinal ring. The internal oblique muscle is sutured to the shelving edge of the inguinal ligament, again leaving a small opening medially for the new internal ring. The external oblique aponeurosis is reapproximated. The skin closure is the same as that used for herniorrhaphy wounds. In children under 8 years of age, the operation usually is performed on an outpatient basis. Despite the arrangement of the external ring almost directly over the new internal ring, which appears conducive to developing a direct hernia, this complication is extremely rare. For high-lying testes that cannot be brought into the low scrotum by the standard orchiopexy (approximately 5 per cent), a two-stage repair is preferred instead of placing great downward traction on the gonad. The lower pole of the tunica may be attached to the pubis or adjacent muscle, or it may be attached to an external cottonoid pledget by means of a pullout stitch of nylon. An interval of approximately 1 year is recommended before the second-stage operation is performed. Zer and associates" were able to position the testis satisfactorily in the low scrotum in 90 per cent of their 62 patients on whom staged orchiorrhaphy was performed. Corkery45 recommended placing the testis and spermatic cord in a Silastic envelope at the first operation to reduce the extensive adhesions between the testis and the inguinal tissues that usually make the second operation more
TESTICULAR UNDESCENT AND TORSION
1313
tedious and bloody. Caution should be taken to avoid injury to the vessels of the gonad during the second operation because subsequent testicular atrophy is not uncommon, whereas the additional benefits of the second operation have not been clearly documented. Fowler and Stephens 46 developed the "long-loop vas" orchiopexy, a technique for correcting the high undescended testis. The spermatic artery and veins are divided high, which permits sufficient mobility to place the gonad into the scrotum in one operation. The testis then derives its blood supply entirely from a secondary vascular loop from the vessels of the vas deferens, collaterals from the deep epigastric vessels, and branches entering the posterior wall of the processus vaginalis in the area of the gubernaculum. The success of this operation depends on the fact that no dissection is performed within the substance of the cord and that division of the spermatic vessels should be as high above the testicle as is feasible to ensure optimal vascularity. Because most authors have reported occasional atrophic testes after division of the spermatic artery, this procedure should be used cautiously and only when other techniques do not appear feasible. Flinn and King<7 described the midline transabdominal approach, especially useful for patients with bilateral high cryptorchidism in whom both testes can be brought down through a single incision. This operation is particularly suitable for patients whose inguinal structures have been distorted from previous operations as well as those with suspected testicular agenesis or intersex malformations. Microsurgical techniques for anastomosis of the spermatic vessels to vessels of the high thigh or branches of the inferior epigastric vessels have been reported with some success in the management of the high undescended testes. Silber and Kelly48 reported the first successful case of microvascular reconstruction in 1976.
Abdominal Exploration When the testicle cannot be located after extensive exploration of the retroperitoneal space, it has been our experience that transperitoneal exploration through the same inguinal incision slightly extended (LaRoque maneuver) is necessary to exclude completely the possible presence of a gonad. The intra-abdominal testis may be missed easily during retroperitoneal dissection because it is suspended in the peritoneal cavity by the mesorchium, as in the normal ovary. Three of our patients who previously underwent extensive retroperitoneal exploration and insertion of scrotal prostheses after failure to identify a gonad, when later explored abdominally were found to have intra-abdominal testes; one of these gonads was malignant.
Malignancy The high incidence of malignant tumors in untreated undescended testes has led Martin and Menck49 and others to focus on the appropriate treatment of the patient first seen after puberty. Comparing the risk of death due to malignancy after orchiopexy with the risk after orchiectomy, they concluded that between the ages of 15 and 50 years, all unilateral undescended inguinal and intra-abdominal testes should be removed. In the case of anorchia, or when the testicle is removed, in most patients, regardless of age, a soft Silastic testicular prosthesis should be placed into the scrotum through the inguinal incision.
COMPLICATIONS Following orchiopexy, complications severe enough to jeopardize function of the gonad occur in fewer than 5 per cent of operations performed by experienced
1314
ERIC
W.
FONKALSRUD
surgeons. The most serious concerns are obstruction of the delicate vascular supply to the testis by direct injury, compression from twisting the vascular pedicle, closing the abdominal musculature too tightly, or from narrowing the vessels by placing them under significant tension as the testis is brought into the scrotum. Because the function of the cryptorchid testis in many instances is less than optimal, there is sufficient indication that the additional insult of vascular injury may worsen the prognosis for function even after the testis is placed into the scrotum. Transient testicular swelling from partial obstruction of lymphatic and venous drainage is common, usually subsiding within 2 to 4 weeks. Retraction of the testis up to the external inguinal ring or higher has been uncommon since the dartos pouch technique of anchoring the testis has been used routinely. Recurrent direct hernia and scrotal hernia are rare after orchiopexy.
RESULTS Studies by Ludwig and Potempa indicate the important role that proper timing plays in determining the success of treatment. 50 In 71 patients who underwent orchiopexy for unilateral undescent between the first and thirteenth year of life, the fertility rate correlated directly with the earlier date of operation. The fertility rate was 87.5 per cent if orchiopexy was performed between the first and second years of life; it was lowered to 57 per cent when the operation was performed between the third and fourth years, to 38.5 per cent if betWeen the fifth and eighth years, and became as low as 25 per cent from the ninth to the twelfth year. After age 14, the fertility rate was less than 14 per cent. While these figures are similar to those of other authors as well as our own experience, much larger series are necessary to corroborate these observations. We also have noted that the fertility rate with unilateral descent is not less than 45 per cent regardless of the age at which orchiopexy is performed. Patients who have high unilateral undescent are more likely to suffer severely abnormal morphologic changes than are those with low-lying testes; the patients with high testes have a lower rate of fertility, and we suspect that the high testis is more likely to produce autoantibodies adversely affecting the contralateral descended testis, and experience a much higher incidence of subsequent malignant degeneration. We therefore remove high-lying unilaterally descended or atrophic testes in most cases before adolescence. In our experience, 96 per cent or more patients with undescended testes will have a concomitant indirect inguinal hernia. Gonads that do descend with hormone therapy in many cases will require herniorrhaphy at a later date, or one must seriously question the initial diagnosis of true cryptorchidism.
SUMMARY The higher the testis resides above the scrotum, the more dysgenetic the morphology is likely to be. High testes are rarely responsive to HCG and should be treated by orchiopexy by the age of 2 to 3 years. The undescended testis does not mature normally after the age of 2 years and may produce adverse effects on the contralateral descended testis, possibly by an autoimmune mechanism. A course of HCG for boys with low-lying undescended testes, both unilateral and bilateral, may produce descent in as many as 15 per cent of patients and may make the technical aspects of orchiopexy easier in those who do not respond. Unilateral
TESTICULAR UNDESCENT AND TORSION
1315
cryptorchid testes that are dysplastic or located high should generally be removed before adolescence.
TORSION OF THE TESTIS
Under normal circumstances, posterior fixation of the epididymis, its close apposition to the testis and incomplete investment by the tunica vaginalis ensure both mobility and relative stability of the testis. Twisting of the testis results in occlusion of the blood supply which, if unrelieved, produces necrosis. If the tunica vaginalis has a high investment on the spermatic cord, the testis is not fixed and intravaginal torsion may occur, which is the most common form of testicular torsion. Torsion also may occur between the epididymis and the testis if the two are separated by an elongated mesorchium. The testes in the newborn and cryptorchid are not fixed in the scrotum and the entire cord may twist, producing extravaginal torsion. After the neonatal period, testicular torsion is almost always associated with the "bell-clapper" fixation abnormality. Testicular torsion is often discovered upon awakening in the morning, suggesting that increased testosterone levels and the elevation and rotation of the testis during the nocturnal sex response cycle may initiate the rotation. The left testicle is affected twice as often as is the right, perhaps related to the fact that the left spermatic cord is usually longer. Torsion of the spermatic cord and testicle causes venous and arterial occlusion, with eventual thrombosis leading to testicular infarction. Damage to the gonad varies with the degree of torsion, its tightness, and its duration. It has been demonstrated experimentally in dogs that four complete twists (1440 degrees) of the spermatic cord produce irreversible changes within 2 hours, whereas one turn (360 degrees) produces no changes up to 12 hours.51 Clinical studies indicate great variability with some patients having intermittent and self-resolving torsion, whereas others have early complete vascular occlusion. Few testes, however, have survived 24 hours of symptomatic torsion. Gradual onset of pain increasing in severity is the initial symptom in more than 80 per cent of patients. Less than one fifth of patients have a history of trauma. Swelling of the scrotum gradually develops, followed by erythema and edema. Nausea, anorexia, and vomiting may occur. The involved side of the scrotum becomes swollen, with dark red discoloration and edema. The testis is exquisitely tender and slight elevation accentuates the pain. Cryptorchid testes are more likely to undergo torsion since they lack fixation. Torsion of the testis should be separated from epididymitis, orchitis, and incarcerated hernia. Elevation of the testicle producing increased pain is diagnostic. A Doppler vascular monitor will show absent arterial flow to the testis with torsion. The treatment for torsion is immediate scrotal exploration with detorsion and bilateral fixation orchiopexy. The scrotal approach provides better visualization and fixation. Mter detorsing the testicle, observe the gonad for 15 to 20 minutes. Only definitely necrotic gonads should be removed at the initial operation. Gonads with questionable viability should be left in place and removed when the lack of viability is determined. Although testicular salvage rates have increased in the past decade, long-term followup results indicate that up to two-thirds of the testes will eventually show significant atrophy. If the viability of the testis is questionable, it should be removed to prevent impairment of spermatogenesis of the contralateral testis.
1316
ERIC
W.
FONKALSRUD
REFERENCES 1. Burton CC: The embryologic development and descent of the testis in relation to congenital hernia. Surg Gynecol Obstet 105:284-289, 1958 2. Lemeh CN: A study of the development and structural relationships of the testis and gubernaculum. Surg Gynecol Obstet 110:164-167, 1960 3. Sonneland SG: Undescended testicle. Surg Gynecol Obstet 40:535-540, 1925 4. Blanchard MG, Josso N: Source of the anti-miillerian hormone synthesized by the fetal testis: Miillerian-inhibiting activity offetal bovine Sertoli cells in tissue culture. Pediatr Res 8:968-973, 1974 5. Jost A: A new look at the mechanisms controlling sex differentiation in mammals. Johns Hopkins Med J 130:38-44, 1972 6. Imperato-McGinley J et al: Steroid 5-alpha reductase deficiency in men: An inherited form of male pseudohermaphroditism. Science 186:1213-1214, 1974 7. Zondek B: Uber die funcktion des ovariums. Z Geburtshife Gynak 90:372-377, 1926 8. Aschheim S: Uber die funcktion des ovariums. Z Geburtshife Gynak 90:387-392, 1926 9. Jost A: Sur Ie role des gonads foetalis dans las differentiation sexuelle somatique de l'embryon du lapin. Cr Assoc Anat 34:255-260, 1947. 10. Nelson WO: Effect of gonadotropic hormone injections upon the hypophysis and sex accessories of experimental cryptorchid rats. Proc Soc Exp BioI Med 31:1192-1195, 1933 11. Womack EB, Koch FC: Undescended testis. Endocrinology 16:267-272, 1932 12. Moore NS, Tapper SM: Cryptorchidism: A theory to explain its etiology. J Urol43:20209,1940 13. Thompson WO, Heckel NJ: Undescended testes: Present status of glandular treatment. JAMA 112:397-402, 1939 14. Zachman M, Prader A, Kind HP et al: Testicular volume during adolescence, crosssectional and longitudinal studies. Helv Paediatr Acta 29:61-64, 1974 15. Browne D: Some anatomical points in operation for undescended testicle. Lancet 1:460464,1933 16. Puri P, Nixon HH: Bilateral retractile testes-Subsequent effect on fertility. J Pediatr Surg 12:563-567, 1977 17. Scorer CG: The descent of the testis. Arch Dis Child 39:605-609, 1964 18. Jones PG: Undescended testes. Aust Paediatr J 2:36-42, 1966 19. Abeyratne MR, Aherne WA, Scott JES: The vanishing testis. Lancet 2:822-826, 1969 20. Staedtler F, Hartmann R: Histologische und morphometrische Untersuchungen zum prapubenilen Hodenwachstum bei normal entwickelten und zerebral geschadigten Knaben. Dtsch Med Wochenschr 97:104-109, 1972 21. Mengel W, Zimmermann FA, Hecker WCh: Timing of repair for undescended testes. In Fonkalsrud EW, Mengel W (eds): The Undescended Testis. Chicago, Year Book Medical, 1981, p 170 22. Hedinger CHR: Histological data in cryptorchidism. Cryptorchidism, diagnosis and treatment. Pediatr Adolesc Endocrinol 6:3-8, 1979 23. Hadziselmovic F: Cryptorchidism: Ultrastructure of normal and cryptorchid testis development. Adv Anat Embryol Cell BioI 53(3):3-9, 1977 24. Wronecki CHR, Slowikoski J, Zarzycki Jet al: Elektron-enmikroskopische Untersuchengen am retinierten Hoden. Z Kinderchir 20:158-163, 1977 25. Holzner H, Gasser G: Hodenbiopsie bei Kryptorchismus. Wien Med Wochenschr 116:311-315, 1966 26. Bay V, Mattaes P, Schirren C: Morphologische befunde bei Hodenhochstand. Chirurgie 39:331-335, 1968 27. Hasli po: Zur problematik der behandlung der Kryptorchismus. Acta Urol 2:107-111, 1971 28. Staedtler F: Die Normal und Gestarte Prapuberale Hodenentwicklung des Menschen. Stuttgart, Gustav Fischer, 1973 29. Shirai M, Matsushita S, Kagayama M et al: Histological changes of the scrotal testis in unilateral cryptorchidism. Tohoku J Exp Med, 90:363-367, 1966 30. Mengel W: Klinische und Experimentelle Studien zum Kryptorchismus Problem. Munchen, Medical Habilitation, 1978
TESTICULAR UNDESCENT AND TORSION
1317
31. Mengel W, Zimmermann FA: Immunological aspects of cryptorchidism. In Fonkalsrud EW, Mengel W (eds): The Undescended Testis. Chicago, Year Book Medical, 1981, p 184 32. Murthy GG, Peress NS, Kahn SA: Demonstration of antibodies to testicular basement membrane by immunofluorescence in a patient with multiple primary endocrine deficiencies. J Clin Endocrinol Metabol 42:637-640, 1976 33. Haensch R: Autoimmunopathologische Fertilitatestorungen des Mannes. Arch Klin Exp Dermatol237:61-66, 1970 34. Johnson MH: An immunological barrier in the guinea pig testis. J Pathol 101:129-134, 1970 35. Tung KSK, Unanue ER, Dixon FJ: Pathogenesis of experimental allergic orchitis. I. Transfer with immune lymph node cells. J Immunol106:1453-1458, 1971 36. Tung KSK, Unanue ER, Dixon FJ: Pathogenesis of experimental allergic orchitis. II. The role of antibody. J Immunol106:1463-1469, 1971 37. Kiesewetter WB, Shull WR, Fettermann GH: Histological changes in the testis following anatomically successful orchiopexy. J Pediatr Surg 4:59-65, 1969 38. Hecker WC: Neue Gesicktspunkte zum Kryptorchismus Problem. Miinch Med Wochenschr 113:1125-1131, 1971 39. Kleinteich B, Schickendanz H: Morphometric follow-up examinations of operated dystopic testicles. Z Kinderchir 20:261-266, 1977 40. Knorr D: Fertility after HCG treatment of maldescended testes in cryptorchidism: Diagnosis and treatment. Pediatr Adolesc Endocrinol 6:215-220, 1979 41. Hadziselmovic F: Current treatment of cryptorchidism. Dial Pediatr UroI6(4):2-3, 1983 42. Rajfer J, Handelsman DJ, SwerdiofI RS, et al: Hormonal therapy of cryptorchidism: A randomized, double-blind study comparing HCG and gonadotropin-releasing hormone. N Engl J Med 314:466-470, 1986 43. Fonkalsrud EW: The undescended testis. Curr Probl Surg 15(3):35-47, 1978 44. Zer M, Wolloch Y, Dintsman M: Staged orchiorrhaphy. Arch Surg 110:387-390, 1975 45. Corkery JJ: Stated orchiopexy: A new technique. J Pediatr Surg 10:515-519, 1975 46. Fowler R, Stephens FD: The role of testicular vascular anatomy in the salvage of high undescended testis. Aust NZ J Surg 29:92-97, 1959 47. Flinn RA, King LR: Experiences with the midline transabdominal approach in orchiopexy. Surg Gynecol Obstet 131:285-290, 1971 48. Silber SJ, Kelly J: Successful autotransplantation of an intra-abdominal testis to the scrotum by microvascular technique. J Urol115:452-456, 1976 49. Martin DC, Menck HR: The undescended testis: Management after puberty. J Urol 114:77-82, 1975 SO. Ludwig G, Potempa J: Der optimale Zeitpunkt der Behandlung des Kryptorchismus. Dtsch Med Wochenschr 100:680-686, 1975 51. Sonda LP, Lapides J: Experimental torsion of the spermatic cord. Surg Forum 12:502, 1961 Department of Pediatric Surgery UCLA School of Medicine Los Angeles, California 90024
0031-3955/87 $0.00
+ .20
Testicular Undescent and Torsion
Eric W. Fonkalsrud, MD*
EMBRYOLOGY The embryonic development of the testis may be divided into three phases: intra-abdominal (1-7 months), canalicular (7-8 months), and scrotal (8--9 months). As the anterior abdominal wall develops, the gonad becomes attached at the site of the future inguinal canal by fibers of the developing gubernaculum. 1 The contractile muscle fibers of the gubernaculum are believed to cause the testicle to migrate through the inguinal canal in the seventh fetal month. The gubernaculum is attached superiorly to the proximal tip of the vas deferens and is believed to divided distally into several tails extending to the dartos muscle in the scrotum, Colles' fascia in the perineum, the pubic tubercle and crest, the inguinal ligament and the fascia lata in the femoral triangle. 2 Although the testicle normally follows the course of the scrotal extension, occasionally it may follow one of the other gubernacular tails to an ectopic location in the perineal, suprapubic, or femoral areas. The descent of the testis is attributed to the three combined forces of intraabdominal pressure, intramuscular pressure due to the contraction of the muscles draped around the canal, and the guidance and active contraction of the gubernaculum. 3 The testis and gubernaculum are covered by peritoneum before the descent begins along the inguinal canal, dorsal to the peritoneal cavity. Before and during descent, the testis and spermatic cord enlarge and the vessels of the cord lengthen and become tortuous, increasing the mobility of the testis. The testis then progresses through the inguinal canal and descends into the scrotum. The testis carries with it an extension of the peritoneal cavity, the processus vaginalis. Later, the testis becomes covered by a reflected fold of the processus, although it lies entirely outside the peritoneal cavity. After the gonad reaches the scrotum, the gubernaculum becomes indistinct as an identifiable structure. Many aspects of the embryologic and morphologic development of the testicle remain undefined. *Professor and Chief of Pediatric Surgery, UCLA School of Medicine, Los Angeles, California From the Department of Surgery, UCLA School of Medicine, Los Angeles, California
Pediatric Clinics of North America-Vol. 34, No.5, October 1987
1305
1306
ERIC
W.
FONKALSRUD
HORMONAL INFLUENCES The Sertoli cells of the testis produce a locally active substance (mullerianinhibiting substance) responsible for regression of the paramesonephric (mullerian) duct. 4 The Leydig cells produce locally acting testosterone responsible for differentiating the mesonephric duct into wolffian structures. S Testicular secretion of testosterone into the general circulation and its peripheral conversion to dihydrotestosterone is responsible for masculinizing the external genitalia. 6 Defects in any of these testicular functions can result in conditions such as male pseudohermaphroditism, with or without cryptorchidism. Zondek7 and Aschheim 8 describe the presence of gonad-stimulating hormones in the urine of pregnant women that was different from that found in urine from postmenopausal women. Jost9 showed that a sufficiently large amount of circulating male hormone in the fetus may cause testicular descent. Zondek7 noted that high levels of gonadotropic hormones are present in the human maternal circulation until the third trimester, when they begin to drop. Nelson lO demonstrated that maternal gonadotropic hormones stimulate production of androgenic hormones from the fetal testis. High levels of gonadotropin are present in the circulation during the last eight weeks of fetal development, and then are almost absent from birth until about 10 to 12 years of age, when the levels rise again. 11 Testicular descent is believed to be greatly influenced by the presence of these demonstrable hormones during fetal development; however, there is no clear evidence that true cryptorchid testes with mechanical obstruction will descend further in response to exogenous or endogenous hormones after the first three months of life. 12.13 Failure of the testicle to descend during the third trimester may be related either to the inadequacy of the hormones, or more likely to the failure of the testis to respond to them, since over 75 per cent of undescended testes are unilateral. Normal testicular volume is less than 2 ml up to the age of 11 years. At age 12 years, the volume ranges from 2 to 5 ml; at age 13 years from 5 to 10 ml and at 15 years from 12 to 14 ml. 14
TYPES OF UNDESCENDED TESTES Retractile Testes An extensive study of human inguinal anatomy by Browne lS indicated that more than three fourths of the testes not located in the scrotum of children were held in higher pOSition by an "overactive" cremaster muscle. Retractile testes are believed to ascend from the scrotum because of an overactive cremaster muscle and failure of complete attachment of the lower pole of the testicle to the scrotum by the gubernaculum. By this normal muscular action, the testes are held high spontaneously during periods of stimulation. Such testes usually descend into the scrotum spontaneously when the child is asleep or relaxes, as in a warm bath. Retractile testes are usually bilateral, in contrast to true undescended testes. At puberty the testicle becomes larger than the external ring, the cremaster muscle becomes less active, and the retractile testis usually remains in the scrotum. If at any time the testis can be manipulated into the low scrotum, the patient has a retractile testis and parents can be reassured that the testis will eventually reside in the normal scrotal position, usually well before puberty. Testicular volume and function in retractile testicles are believed to be normal in adulthood. 16
TESTICULAR UNDESCENT AND TORSION
1307
Ectopic Testes The true cryptorchid testis should be distinguished from an ectopic testis that has progressed normally through the inguinal canal and emerged from the external ring but has been directed away from the scrotum into the thigh, the suprapubic area, or the perineum. Transverse ectopia to the contralateral groin has been reported. The rarity of true ectopia is evidenced by the fact that in a review of more than 153 male infants with testicular undescent, Scorer'7 found no infants with true ectopia. Approximately 80 per cent of ectopic testes are unilateral, usually normal in size, with normal spermatogenic and androgenic function. Regardless of location, they should be placed into the scrotum surgically. Attempts to move ectopic testes into the scrotum with hormone therapy have been ineffective. 18
Anorchia Normal male (wolffian) ductal development depends on fetal androgenic stimulation from the differentiated testis. With the complete absence of testicular tissue, female (miillerian) ductal development differentiates into the feminine configuration. Rarely, one testis may fail to develop, more commonly on the right and occasionally associated with ipsilateral agenesis of the kidney and ureter. The vas deferens in these patients is usually hypoplastic and ends blindly at the internal inguinal ring. The ipsilateral scrotum is often underdeveloped. Anorchia has been reported to occur in from 3.3 per cent to 5.2 per cent of boys operated on for cryptorchidism. '8 , 19 Anorchia is unilateral in approximately 85 per cent of cases. The surgeon should be encouraged to seek a nonpalpable, high undescended testis, inasmuch as total absence is uncommon. On rare occasions no viable testicular tissue on either side is evident, although the external genitalia are fully differentiated in masculine configuration at birth and a vestigial vas deferens terminates blindly in the abdomen. Torsion or obstruction to testicular blood supply is believed to play a role in this "vanishing testis" syndrome. Puberty is delayed, characterized by persistent elevations of plasma FSH and LH levels and low plasma testosterone levels. Although abdominal ultrasound and computer-assisted tomography (CT) may be of some help in identifying intra-abdominal testes, surgical exploration is necessary to establish the diagnosis. Exogenously administered testosterone in early adolescence produces a gratifying response of male sexual maturation. Testicular prostheses can be inserted after testosterone therapy has enlarged the scrotum.
Undescended Testes It is generally recognized that the undescended testis that does not descend into the scrotum spontaneously, with hormone therapy or with operation, by the fourth year of life probably will not achieve normal spermatogenic function in adolescence. It is further recognized that the higher the testis resides above the scrotum, the more dysgenetic the morphologic features of the gonad are likely to be. Most cryptorchid testes are prevented from reaching the scrotum because the spermatic artery is shorter than normal. It is not known whether blood flow in the spermatic artery of the undescended testis is less than that in the normal descended gonad. Inasmuch as more than 75 per cent of true undescended testes occur unilaterally, a specific hormonal deficiency that might account for the cryptorchidism has been difficult to identify. Children with bilateral cryptorchidism are more likely to have an endocrinologic disturbance with hormonal deficiency than are those with unilateral undescent; they also tend to have anatomic disturbances limiting descent of the testes (e.g., exstrophy of the bladder, gastroschisis, prune belly syndrome and a variety of other disorders). Approximately 8 per cent of undescended testes are primarily dysgenetic,
1308
ERIC
W.
FONKALSRUD
AGE DISTRIBUTION OF SPERMATOGONIA IN DESCENDED AND UNDESCENDED TESTICLES w
S
1000
[J Descended
In
:::>
•
I-
Undescended
~ Z W
IZ
150
o U Z
50 30 20
~
10
oC) o ~
c:::
W 0..
(/)
o
~
2
3 4
5 6 7 8 9 10 11 AGE IN YEARS
12 13 15
Figure 1. Average spermatogonia counts per tubule (average of 50 tubules counted) obtained from 237 unilaterally descended testes and from 515 unilaterally undescended testes revealed by biopsies taken from children up to the age of 15 years. The striped area shows the normal range of spermatogonia counts of bilaterally descended testes. [J Descended, • undescended. (From Mengel W, Zimmermann FA, Hecker W: The Undescended Testes. Chicago, Year Book Medical, 1981; with permission.)
usually high in location, and will never experience adequate spermatogenic function despite any form of therapy. Nonetheless, most undescended testes that have interstitial tissue and Leydig cells will produce sufficient testosterone to cause virilization. The incidence of true undescent ranges from 20 to 30 per cent in premature infants and from 1.8 to 4.0 per cent in mature newborn infants. Subsequent descent within the first 9 months of life occurs in most infants with originally undescended testes. '1 After the first year of life, true undescent is pathologic, occurring in approximately 0.7 per cent at that age. Contrary to previous views, it has been shown by examination of testicular weight, diameter of seminiferous tubules and spermatogonia counts that the young child's gonads have a linear development pattern before puberty. 20 Damaging influences causing morphologic changes in the undescended testis begin by the end of the second year. 21 Considerable controversy has existed regarding the age at which damage to a dystopic testis begins. Using the spermatogonia count as well as qualitative examination of the ultrastructure of interstitial tissue, Mengel et al. was able to show several significant features in 578 malpositioned" testes. 21 In almost all cases, the undescended testis showed no histomorphologic changes during the first two years of life. The mean values of spermatogonia counts were in the normal range; however, after the second year, the spermatogonia counts decreased significantly. The spermatogonia counts in these patients were within the range of 10, indicating that they remained low until puberty (lower limit for normal is 30; Fig. 1). In 1974, Redinger evaluated 619 testicular biopsies from 450 boys with unilateral and bilateral cryptorchidism between the ages of 2 months and 10 years, 22 noting that the mean spermatogonia counts dUring the first year of life were equal to those found in normally descended testes. A difference in the spermatogonia
TESTICULAR UNDESCENT AND TORSION
1309
counts between normal and cryptorchid testes was observed during the second and third year, but after the third year, the mean spermatogonia values from cryptorchid testes were significantly lower than normal and remained at the same level until the beginning of puberty. There was no difference in the spermatogonia counts between unilateral and bilateral cryptorchid testes of the same type. It was suggested by this author that a reduced number of spermatogonia may be acquired during the early stages of development, although he never found complete absence of spermatogonia. Electron microscopic examination of testicular connective tissue shows that with increasing age, the undescended testis tends to degenerate, leading to interstitial enlargement and fibrosis. There is no difference in extent of interstitial tissue and in ultrastructural appearance between an undescended and a descended testis during the first year of life. After the fourth year, however, increasing fibrosis appears with interstitial tissue of the undescended testis enlarged compared to that of bilateral descended testes.21 Early ultrastructural morphologic changes in cryptorchid testes have been demonstrated in the second and third years of life.23, 24 It remains unclear whether the underlying mechanism is a primary diminution of spermatogonia accompanied by atrophy of the tubules with secondary thickening and fibrosis, or an atrophy of the germinal epithelium owing to diminished vascularization caused by primary expansion of the connective tissue. It has long been of clinical interest that not only the dystopic but also the contralateral descended testis shows abnormal morphologic changes during the early years of childhood. Several authors 25 , 26 have found damage in the germinal epithelium of the orthotopic testis in 30 to 50 per cent of cases of contralateral undescent. Hasli observed such a marked decrease in spermatogonia counts in every sixth patient with unilateral undescent that subsequent infertility could be predicted. 27 Using a morphometric test, Staedtler showed that the spermatogonia count is lowered in both orthotopic and dystopic testes compared with controls. 28 Histological examination of 262 biopsies from unilaterally descended testes in patients with contralateral undescent showed an abnormal germinal epithelium in 61 per cent (Fig. 2). Mengel et al. confirmed previous observations that the spermatogonia counts from unilaterally descended testes are considerably higher than those from unilaterally undescended testes, but they have been lower than mean values from normal controls. 21 It has been our experience that the spermatogonia counts and fertility of patients with very low-lying testes are far superior to those in patients who have higher-lying testes, regardless of the form of treatment. Experimental studies in dogs reported by several authors indicate that experimental malposition of one testis induces pathomorphologic changes in the contralateral descended testis as measured by lower spermatogonia counts. 29, 30 The presence of autoantibodies against spermatozoa has been recognized for many years and demonstrated in large series of patients who have various testicular disorders. 31 Murthy et al. demonstrated circulating antibodies against basement membrane of the tubular wall as well as against the germinal cells in a patient with multiple endocrinologic disorders.32 Haensch found a close correlation between the presence of autoantibodies against spermatozoa and conditions causing testicular dystopia. 33 According to the results of Johnson34 and Tung et al. 35, 36 the basement membrane of the seminiferous tubules acts as a immunologic barrier that under normal circumstances keeps antibodies from penetrating into the seminiferous tubules. Under pathologic conditions, the basement membrane may become porous and several parts of the seminiferous tubules may be exposed to antibodies, possibly leading to an antigen-antibody reaction. Azathioprine has improved the spermatogonia counts in both dystopic and orthotopic testes of experimentally cryptorchid dogs. 31
1310
ERIC
W.
FONKALSRUD
SPERMATOGONIA COUNTS Unilaterally Orthotopic (262 biopsies)
Un i1atera lIy Dystopic (262 biopsies)
(From Mengel et ai, 1981)
Figure 2. Spermatogonia counts from biopsies obtained from 262 children with unilaterally undescended testes (50 tubules counted per biopsy). Whereas 84 per cent of undescended testes had spermatogonia counts of less than 30 per tubule (abnormal), 62 per cent of the contralateral descended testes had abnormal spermatogonia counts. (From Mengel W, Zimmermann FA, Hecker W: The Undescended Testes. Chicago, Year Book Medical, 1981; with permission.)
Kiesewetter et al. 37 as well as others38• 39 have demonstrated that young children who undergo orchiopexy subsequently show an increase in the spermatogonia count. This observation is verified in the experimental dog with unilateral cryptorchidism in which a significant increase in spermatogonia count can be demonstrated after scrotal orchiopexy.
TREATMENT The primary criterion for determining the successful treatment of cryptorchidism and the optimal date for initiating therapy is delayed fertility, not merely the presence of a palpable testis in the scrotum. It is difficult to compare the results among patients who have undergone different types of fertility studies after orchiopexy, but it is apparent that published fertility results up to 10 years ago have in general been unsatisfactory. The main reason for the .eported low fertility rates is that nearly all of the patients received no treatment until after the age of 6 years. In our series of over 200 patients operated on before the age of 5 years, the sperm count exceeded 20 million per ml in over three fourths of patients with unilateral undescent who did not have atrophic or absent testes. Human chorionic gonadotropin (HCG) therapy produced descent only in testes considered retractile or high scrotal, and almost all resumed the elevated position 1 month after therapy. Following completion of a course of therapy including 10,000 units of HCG over a 2-week period, only patients with testes located in these positions responded with descent into the scrotum. A course of HCG prior to orchiopexy enlarges the testis
TESTICULAR UNDESCENT AND TORSION
1311
Figure 3. A, Lengthy course of the spermatic artery descending from the aorta through the internal inguinal ring to the undescended testis in the inguinal canal. B, By transposing the internal inguinal ring medially to the pubis, the course of the spermatic artery may be lengthened effectively to permit the testis to be placed into the scrotum, the basis of the standard orchiopexy. (From Fonkalsrud EW: Curr Probl Surg 15:35--47, 1978; with permission.)
and the spermatic vessels, making the technical repair easier. The policy recommended by Mengel et al. to operate on children only if descent is not induced by a course of HCG before the age of 2 years has considerable merit. 21 The major problem in our experience is the unwillingness of the family to have the child receive a series of intramuscular injections before operation when the likelihood of HCG producing descent is less than 10 per cent. The fertility rate reported by Knorr after HCG therapy is 46 per cent and is increased after orchiopexy by another 25 per cent. Although the experience with LHRH in causing descent has had limited trial in the United States, preliminary studies indicate that the results have been no better than with the use of HCG. Nonetheless, studies by Hadziselimovic41 have strongly suggested that LHRH produces descent in most patients with an empty scrotum on whom the agent is used. Double-blind control studies by Rajfer et al. and others have failed to show improvement in producing descent with the use of LHRH.42
Surgical Treatment Current evidence suggests that the optimal time for performing orchiopexy is before the age of 4 and probably as early as 2 years. The technique of orchiopexy currently in general use has been described and illustrated by several authors. 43 The objective of the repair is to alter the course of the spermatic artery from the renal pedicle, through the internal inguinal ring, to the external inguinal ring, and to create in its place a direct line from the renal pedicle to the scrotum (Fig. 3). A small incision is made through the lowermost abdominal skin crease, and the external oblique aponeurosis is opened in the direction of its fibers through the external ring. The testicle usually is found protruding through the external ring
1312
ERIC W. FONKALSRUD
inferior to the internal oblique muscle with attachments to the pubis. The testis with its surrounding tunica vaginalis is mobilized from the gubernaculum and often tenacious surrounding attachments, permitting it to be elevated with gentle traction. The cremaster muscle is mobilized gently from the spermatic vessels and the vas deferens up to the level of the internal inguinal ring. The internal oblique muscle is divided lateral to the internal ring for approximately 1 cm to obtain better exposure. The inferior epigastric artery and veins are divided and the transversalis fascia is opened widely through the internal ring to permit wide exposure of the retroperitoneal space. The accompanying hernia sac, which is present in approximately 90 per cent of patients, is separated from the spermatic vessels and the vas, often a delicate maneuver because the structures are tenaciously adherent and the sac tears easily. The maneuver can be facilitated by injecting a small amount of saline through a small-gauge needle between the hernia sac and the cord structures and then gently developing a plane by blunt dissection with a fine clamp. High ligation of the hernia sac is performed with a fine transfixion suture. The gonad is inspected to note its size, consistency, and any abnormal features. Biopsy is not recommended routinely because of the risk of further injury to the delicate organ, especially in the young child, unless any unusual features are apparent, or if the child is older than 12 years. A thin wedge biopsy running longitudinally on the side opposite the epididymis is preferred, closing the wound with fine continuous suture. The testicle is placed into the tunica, the proximal end of which is closed loosely to prevent dislodgment outside the sac. The dissection is continued into the retroperitoneal space by elevating the peritoneum, sharply dividing the lateral spermatic fascia, and bluntly mobilizing the spermatic vessels up to the lower pole of the kidney and the vas over to the bladder. The scrotum is forcibly stretched by inserting a finger through the wound to the lowermost portion of the sac. A small incision is made through the scrotal skin at this point and a space sufficiently large to accommodate the testis is developed between the dartos muscle and the scrotal skin by blunt dissection. A small opening is then placed in the dartos fascia and muscle layer, through which a clamp is passed superiorly to direct the testicle downward to the scrotum. Twisting the spermatic vessels must be avoided. The upper edge of the tunica is stitched to the dartos layer circumferentially to prevent upward displacement or subsequent torsion, and the testis placed subcutaneously. The scrotal skin is closed loosely with fine absorbable sutures. The transversalis fascia is then closed with nonabsorbable sutures, leaving a small opening just lateral to the pubis to function as the new internal inguinal ring. The internal oblique muscle is sutured to the shelving edge of the inguinal ligament, again leaving a small opening medially for the new internal ring. The external oblique aponeurosis is reapproximated. The skin closure is the same as that used for herniorrhaphy wounds. In children under 8 years of age, the operation usually is performed on an outpatient basis. Despite the arrangement of the external ring almost directly over the new internal ring, which appears conducive to developing a direct hernia, this complication is extremely rare. For high-lying testes that cannot be brought into the low scrotum by the standard orchiopexy (approximately 5 per cent), a two-stage repair is preferred instead of placing great downward traction on the gonad. The lower pole of the tunica may be attached to the pubis or adjacent muscle, or it may be attached to an external cottonoid pledget by means of a pullout stitch of nylon. An interval of approximately 1 year is recommended before the second-stage operation is performed. Zer and associates" were able to position the testis satisfactorily in the low scrotum in 90 per cent of their 62 patients on whom staged orchiorrhaphy was performed. Corkery45 recommended placing the testis and spermatic cord in a Silastic envelope at the first operation to reduce the extensive adhesions between the testis and the inguinal tissues that usually make the second operation more
TESTICULAR UNDESCENT AND TORSION
1313
tedious and bloody. Caution should be taken to avoid injury to the vessels of the gonad during the second operation because subsequent testicular atrophy is not uncommon, whereas the additional benefits of the second operation have not been clearly documented. Fowler and Stephens 46 developed the "long-loop vas" orchiopexy, a technique for correcting the high undescended testis. The spermatic artery and veins are divided high, which permits sufficient mobility to place the gonad into the scrotum in one operation. The testis then derives its blood supply entirely from a secondary vascular loop from the vessels of the vas deferens, collaterals from the deep epigastric vessels, and branches entering the posterior wall of the processus vaginalis in the area of the gubernaculum. The success of this operation depends on the fact that no dissection is performed within the substance of the cord and that division of the spermatic vessels should be as high above the testicle as is feasible to ensure optimal vascularity. Because most authors have reported occasional atrophic testes after division of the spermatic artery, this procedure should be used cautiously and only when other techniques do not appear feasible. Flinn and King<7 described the midline transabdominal approach, especially useful for patients with bilateral high cryptorchidism in whom both testes can be brought down through a single incision. This operation is particularly suitable for patients whose inguinal structures have been distorted from previous operations as well as those with suspected testicular agenesis or intersex malformations. Microsurgical techniques for anastomosis of the spermatic vessels to vessels of the high thigh or branches of the inferior epigastric vessels have been reported with some success in the management of the high undescended testes. Silber and Kelly48 reported the first successful case of microvascular reconstruction in 1976.
Abdominal Exploration When the testicle cannot be located after extensive exploration of the retroperitoneal space, it has been our experience that transperitoneal exploration through the same inguinal incision slightly extended (LaRoque maneuver) is necessary to exclude completely the possible presence of a gonad. The intra-abdominal testis may be missed easily during retroperitoneal dissection because it is suspended in the peritoneal cavity by the mesorchium, as in the normal ovary. Three of our patients who previously underwent extensive retroperitoneal exploration and insertion of scrotal prostheses after failure to identify a gonad, when later explored abdominally were found to have intra-abdominal testes; one of these gonads was malignant.
Malignancy The high incidence of malignant tumors in untreated undescended testes has led Martin and Menck49 and others to focus on the appropriate treatment of the patient first seen after puberty. Comparing the risk of death due to malignancy after orchiopexy with the risk after orchiectomy, they concluded that between the ages of 15 and 50 years, all unilateral undescended inguinal and intra-abdominal testes should be removed. In the case of anorchia, or when the testicle is removed, in most patients, regardless of age, a soft Silastic testicular prosthesis should be placed into the scrotum through the inguinal incision.
COMPLICATIONS Following orchiopexy, complications severe enough to jeopardize function of the gonad occur in fewer than 5 per cent of operations performed by experienced
1314
ERIC
W.
FONKALSRUD
surgeons. The most serious concerns are obstruction of the delicate vascular supply to the testis by direct injury, compression from twisting the vascular pedicle, closing the abdominal musculature too tightly, or from narrowing the vessels by placing them under significant tension as the testis is brought into the scrotum. Because the function of the cryptorchid testis in many instances is less than optimal, there is sufficient indication that the additional insult of vascular injury may worsen the prognosis for function even after the testis is placed into the scrotum. Transient testicular swelling from partial obstruction of lymphatic and venous drainage is common, usually subsiding within 2 to 4 weeks. Retraction of the testis up to the external inguinal ring or higher has been uncommon since the dartos pouch technique of anchoring the testis has been used routinely. Recurrent direct hernia and scrotal hernia are rare after orchiopexy.
RESULTS Studies by Ludwig and Potempa indicate the important role that proper timing plays in determining the success of treatment. 50 In 71 patients who underwent orchiopexy for unilateral undescent between the first and thirteenth year of life, the fertility rate correlated directly with the earlier date of operation. The fertility rate was 87.5 per cent if orchiopexy was performed between the first and second years of life; it was lowered to 57 per cent when the operation was performed between the third and fourth years, to 38.5 per cent if betWeen the fifth and eighth years, and became as low as 25 per cent from the ninth to the twelfth year. After age 14, the fertility rate was less than 14 per cent. While these figures are similar to those of other authors as well as our own experience, much larger series are necessary to corroborate these observations. We also have noted that the fertility rate with unilateral descent is not less than 45 per cent regardless of the age at which orchiopexy is performed. Patients who have high unilateral undescent are more likely to suffer severely abnormal morphologic changes than are those with low-lying testes; the patients with high testes have a lower rate of fertility, and we suspect that the high testis is more likely to produce autoantibodies adversely affecting the contralateral descended testis, and experience a much higher incidence of subsequent malignant degeneration. We therefore remove high-lying unilaterally descended or atrophic testes in most cases before adolescence. In our experience, 96 per cent or more patients with undescended testes will have a concomitant indirect inguinal hernia. Gonads that do descend with hormone therapy in many cases will require herniorrhaphy at a later date, or one must seriously question the initial diagnosis of true cryptorchidism.
SUMMARY The higher the testis resides above the scrotum, the more dysgenetic the morphology is likely to be. High testes are rarely responsive to HCG and should be treated by orchiopexy by the age of 2 to 3 years. The undescended testis does not mature normally after the age of 2 years and may produce adverse effects on the contralateral descended testis, possibly by an autoimmune mechanism. A course of HCG for boys with low-lying undescended testes, both unilateral and bilateral, may produce descent in as many as 15 per cent of patients and may make the technical aspects of orchiopexy easier in those who do not respond. Unilateral
TESTICULAR UNDESCENT AND TORSION
1315
cryptorchid testes that are dysplastic or located high should generally be removed before adolescence.
TORSION OF THE TESTIS
Under normal circumstances, posterior fixation of the epididymis, its close apposition to the testis and incomplete investment by the tunica vaginalis ensure both mobility and relative stability of the testis. Twisting of the testis results in occlusion of the blood supply which, if unrelieved, produces necrosis. If the tunica vaginalis has a high investment on the spermatic cord, the testis is not fixed and intravaginal torsion may occur, which is the most common form of testicular torsion. Torsion also may occur between the epididymis and the testis if the two are separated by an elongated mesorchium. The testes in the newborn and cryptorchid are not fixed in the scrotum and the entire cord may twist, producing extravaginal torsion. After the neonatal period, testicular torsion is almost always associated with the "bell-clapper" fixation abnormality. Testicular torsion is often discovered upon awakening in the morning, suggesting that increased testosterone levels and the elevation and rotation of the testis during the nocturnal sex response cycle may initiate the rotation. The left testicle is affected twice as often as is the right, perhaps related to the fact that the left spermatic cord is usually longer. Torsion of the spermatic cord and testicle causes venous and arterial occlusion, with eventual thrombosis leading to testicular infarction. Damage to the gonad varies with the degree of torsion, its tightness, and its duration. It has been demonstrated experimentally in dogs that four complete twists (1440 degrees) of the spermatic cord produce irreversible changes within 2 hours, whereas one turn (360 degrees) produces no changes up to 12 hours.51 Clinical studies indicate great variability with some patients having intermittent and self-resolving torsion, whereas others have early complete vascular occlusion. Few testes, however, have survived 24 hours of symptomatic torsion. Gradual onset of pain increasing in severity is the initial symptom in more than 80 per cent of patients. Less than one fifth of patients have a history of trauma. Swelling of the scrotum gradually develops, followed by erythema and edema. Nausea, anorexia, and vomiting may occur. The involved side of the scrotum becomes swollen, with dark red discoloration and edema. The testis is exquisitely tender and slight elevation accentuates the pain. Cryptorchid testes are more likely to undergo torsion since they lack fixation. Torsion of the testis should be separated from epididymitis, orchitis, and incarcerated hernia. Elevation of the testicle producing increased pain is diagnostic. A Doppler vascular monitor will show absent arterial flow to the testis with torsion. The treatment for torsion is immediate scrotal exploration with detorsion and bilateral fixation orchiopexy. The scrotal approach provides better visualization and fixation. Mter detorsing the testicle, observe the gonad for 15 to 20 minutes. Only definitely necrotic gonads should be removed at the initial operation. Gonads with questionable viability should be left in place and removed when the lack of viability is determined. Although testicular salvage rates have increased in the past decade, long-term followup results indicate that up to two-thirds of the testes will eventually show significant atrophy. If the viability of the testis is questionable, it should be removed to prevent impairment of spermatogenesis of the contralateral testis.
1316
ERIC
W.
FONKALSRUD
REFERENCES 1. Burton CC: The embryologic development and descent of the testis in relation to congenital hernia. Surg Gynecol Obstet 105:284-289, 1958 2. Lemeh CN: A study of the development and structural relationships of the testis and gubernaculum. Surg Gynecol Obstet 110:164-167, 1960 3. Sonneland SG: Undescended testicle. Surg Gynecol Obstet 40:535-540, 1925 4. Blanchard MG, Josso N: Source of the anti-miillerian hormone synthesized by the fetal testis: Miillerian-inhibiting activity offetal bovine Sertoli cells in tissue culture. Pediatr Res 8:968-973, 1974 5. Jost A: A new look at the mechanisms controlling sex differentiation in mammals. Johns Hopkins Med J 130:38-44, 1972 6. Imperato-McGinley J et al: Steroid 5-alpha reductase deficiency in men: An inherited form of male pseudohermaphroditism. Science 186:1213-1214, 1974 7. Zondek B: Uber die funcktion des ovariums. Z Geburtshife Gynak 90:372-377, 1926 8. Aschheim S: Uber die funcktion des ovariums. Z Geburtshife Gynak 90:387-392, 1926 9. Jost A: Sur Ie role des gonads foetalis dans las differentiation sexuelle somatique de l'embryon du lapin. Cr Assoc Anat 34:255-260, 1947. 10. Nelson WO: Effect of gonadotropic hormone injections upon the hypophysis and sex accessories of experimental cryptorchid rats. Proc Soc Exp BioI Med 31:1192-1195, 1933 11. Womack EB, Koch FC: Undescended testis. Endocrinology 16:267-272, 1932 12. Moore NS, Tapper SM: Cryptorchidism: A theory to explain its etiology. J Urol43:20209,1940 13. Thompson WO, Heckel NJ: Undescended testes: Present status of glandular treatment. JAMA 112:397-402, 1939 14. Zachman M, Prader A, Kind HP et al: Testicular volume during adolescence, crosssectional and longitudinal studies. Helv Paediatr Acta 29:61-64, 1974 15. Browne D: Some anatomical points in operation for undescended testicle. Lancet 1:460464,1933 16. Puri P, Nixon HH: Bilateral retractile testes-Subsequent effect on fertility. J Pediatr Surg 12:563-567, 1977 17. Scorer CG: The descent of the testis. Arch Dis Child 39:605-609, 1964 18. Jones PG: Undescended testes. Aust Paediatr J 2:36-42, 1966 19. Abeyratne MR, Aherne WA, Scott JES: The vanishing testis. Lancet 2:822-826, 1969 20. Staedtler F, Hartmann R: Histologische und morphometrische Untersuchungen zum prapubenilen Hodenwachstum bei normal entwickelten und zerebral geschadigten Knaben. Dtsch Med Wochenschr 97:104-109, 1972 21. Mengel W, Zimmermann FA, Hecker WCh: Timing of repair for undescended testes. In Fonkalsrud EW, Mengel W (eds): The Undescended Testis. Chicago, Year Book Medical, 1981, p 170 22. Hedinger CHR: Histological data in cryptorchidism. Cryptorchidism, diagnosis and treatment. Pediatr Adolesc Endocrinol 6:3-8, 1979 23. Hadziselmovic F: Cryptorchidism: Ultrastructure of normal and cryptorchid testis development. Adv Anat Embryol Cell BioI 53(3):3-9, 1977 24. Wronecki CHR, Slowikoski J, Zarzycki Jet al: Elektron-enmikroskopische Untersuchengen am retinierten Hoden. Z Kinderchir 20:158-163, 1977 25. Holzner H, Gasser G: Hodenbiopsie bei Kryptorchismus. Wien Med Wochenschr 116:311-315, 1966 26. Bay V, Mattaes P, Schirren C: Morphologische befunde bei Hodenhochstand. Chirurgie 39:331-335, 1968 27. Hasli po: Zur problematik der behandlung der Kryptorchismus. Acta Urol 2:107-111, 1971 28. Staedtler F: Die Normal und Gestarte Prapuberale Hodenentwicklung des Menschen. Stuttgart, Gustav Fischer, 1973 29. Shirai M, Matsushita S, Kagayama M et al: Histological changes of the scrotal testis in unilateral cryptorchidism. Tohoku J Exp Med, 90:363-367, 1966 30. Mengel W: Klinische und Experimentelle Studien zum Kryptorchismus Problem. Munchen, Medical Habilitation, 1978
TESTICULAR UNDESCENT AND TORSION
1317
31. Mengel W, Zimmermann FA: Immunological aspects of cryptorchidism. In Fonkalsrud EW, Mengel W (eds): The Undescended Testis. Chicago, Year Book Medical, 1981, p 184 32. Murthy GG, Peress NS, Kahn SA: Demonstration of antibodies to testicular basement membrane by immunofluorescence in a patient with multiple primary endocrine deficiencies. J Clin Endocrinol Metabol 42:637-640, 1976 33. Haensch R: Autoimmunopathologische Fertilitatestorungen des Mannes. Arch Klin Exp Dermatol237:61-66, 1970 34. Johnson MH: An immunological barrier in the guinea pig testis. J Pathol 101:129-134, 1970 35. Tung KSK, Unanue ER, Dixon FJ: Pathogenesis of experimental allergic orchitis. I. Transfer with immune lymph node cells. J Immunol106:1453-1458, 1971 36. Tung KSK, Unanue ER, Dixon FJ: Pathogenesis of experimental allergic orchitis. II. The role of antibody. J Immunol106:1463-1469, 1971 37. Kiesewetter WB, Shull WR, Fettermann GH: Histological changes in the testis following anatomically successful orchiopexy. J Pediatr Surg 4:59-65, 1969 38. Hecker WC: Neue Gesicktspunkte zum Kryptorchismus Problem. Miinch Med Wochenschr 113:1125-1131, 1971 39. Kleinteich B, Schickendanz H: Morphometric follow-up examinations of operated dystopic testicles. Z Kinderchir 20:261-266, 1977 40. Knorr D: Fertility after HCG treatment of maldescended testes in cryptorchidism: Diagnosis and treatment. Pediatr Adolesc Endocrinol 6:215-220, 1979 41. Hadziselmovic F: Current treatment of cryptorchidism. Dial Pediatr UroI6(4):2-3, 1983 42. Rajfer J, Handelsman DJ, SwerdiofI RS, et al: Hormonal therapy of cryptorchidism: A randomized, double-blind study comparing HCG and gonadotropin-releasing hormone. N Engl J Med 314:466-470, 1986 43. Fonkalsrud EW: The undescended testis. Curr Probl Surg 15(3):35-47, 1978 44. Zer M, Wolloch Y, Dintsman M: Staged orchiorrhaphy. Arch Surg 110:387-390, 1975 45. Corkery JJ: Stated orchiopexy: A new technique. J Pediatr Surg 10:515-519, 1975 46. Fowler R, Stephens FD: The role of testicular vascular anatomy in the salvage of high undescended testis. Aust NZ J Surg 29:92-97, 1959 47. Flinn RA, King LR: Experiences with the midline transabdominal approach in orchiopexy. Surg Gynecol Obstet 131:285-290, 1971 48. Silber SJ, Kelly J: Successful autotransplantation of an intra-abdominal testis to the scrotum by microvascular technique. J Urol115:452-456, 1976 49. Martin DC, Menck HR: The undescended testis: Management after puberty. J Urol 114:77-82, 1975 SO. Ludwig G, Potempa J: Der optimale Zeitpunkt der Behandlung des Kryptorchismus. Dtsch Med Wochenschr 100:680-686, 1975 51. Sonda LP, Lapides J: Experimental torsion of the spermatic cord. Surg Forum 12:502, 1961 Department of Pediatric Surgery UCLA School of Medicine Los Angeles, California 90024