Ectopia
of the Vas Deferens
By John A. Nesbitt II and Lowell R. King Columbus,
Ohio and Durham,
0 Ectopic location of the vas deferens is a rare congenital abnormality that has a spectrum of presentations. Such cases have been associated with anorectal anomalies. Knowledge of distal Wolffian duct embryology may help to explain the developmental steps invoked in these anomalies, as well as provide theories for the variations that may be encountered. Vas deferens development is reviewed, and two cases of vas ectopia are presented to illustrate and lend support to current theories of normal and abnormal vasal embryology. o 1gM by W.B. Saunders Company. INDEX WORDS: Vas deferens. ectopic location.
M
abnormalities ANY OF THE CONGENITAL of the lower urinary tract may be explained by an underlying defect in the proximal mesonephric duct or an abnormally proximal origin for the ureteric bud. Such anomalies would be found in the bladder, and involve the distal ureter and the vas deferens. Conversely, abnormalities seen consequent to altered distal ureteric bud formation are found in the kidney and upper ureter. As originally described by Mackie and Stephens,’ the theoretical embryological development of the distal Wolffian duct is essential in understanding many of the anomalies of the distal ureter, including ureteral ectopia. Later, Gibbons et al2 expanded this theory in an attempt to explain ectopia of the vas deferens. Ectopia of the vas deferens is a rare congenital anomality with multiple variations. The literature contains reports of about 25 cases since the first English description in 1898,3 with a spectrum of intercommunications between the vas and the urinary tract being described. Such cases are likely to be associated with anorectal developmental abnormalities, as well as ureteral ectopia and other distal Wolffian duct anomalies. The usual presentation of such patients is with epididymitis or urinary tract infection. Additionally, an ectopic vas may be discovered serendipitously upon routine examination of genitourinary or other congenital anomalies. Although scrotal pain may occur, many patients are asymptomatic. Two additional cases of vas ectopia are presented here and the embryology is subsequently discussed. CASE REPORTS Case I
J.H. was referred to the pediatric surgery service at Duke University Medical Center at 1 day of age with an imperforate anus. Radiographic studies showed high anorectal agenesis, with the large &al
of Pediatric Surgery,
Vol 25,
No 3 (March), 1990: pp 335-338
North Carolina
bowel terminating well above the puborectalis sling. A voiding cystourethrogram showed right vesicoureteral reflux, international grade 3 of 5, and bilateral reflux into both right and left vasa deferentia (Fig 1). The left ureter was not observed. After a sigmoid colostomy was performed, further evaluation of his urinary tract was accomplished. Ultrasound examination showed the right kidney to be of normal size with no evidence of hydronephrosis. No left kidney was identified. A radionuclide renal scan was obtained, demonstrating normal profusion and function of the right kidney, no renal tissue present in the left renal bal, and no ectopic functioning renal tissue. The patient underwent exploratory surgery. The left vas deferens was found to be continuous with the left ureteral segment, which then entered the bladder and formed an orthopically-placed ureteral orifice. The ureteral stump was ligated and the vas segment was excised to the level of the internal inguinal ring. The right ureter was reimplanted using the cross trigonal method of Cohen. Further extravesical exploration showed a vas deferens on the right that seemed to lie in a normal course and did not communicate with the ureter or bladder. It was suggested that the refhtx into the right vas on the preoperative voiding cystourethrogram had occurred because of an abnormal opening of the vas into the prostatic urethra. A follow-up cystogram at 4 months postoperatively showed no reflux into the right ureter or the right vaa deferens. Intravenous (IV) urography showed no obstruction of the right renal unit, and the child has remained free of infection. Case
2
M.M. was a Cyear-old boy referred to the pediatric urology service for evaluation of dysuria and an absent right testicle. Initial examination showed early reflux into the left vas deferens on filling cystogram and international grade 3/5 left veaicoureteral reflux (Fig 2). Additionally, there was determined to be a partially duplicated collecting system on the right, with a small right kidney, and reflux into a blind ending or obstructed distal ureter. The diagnosis of a ureteral diverticulum was also entertained (Fig 3). A small ipsilateral paraureteral diverticulum was identified as well. Cystoscopy showed a laterally displaced right ureteral or&e. During exploration, a tubular structure was noted to enter the right ureter approximately 4 cm above the ureteroveaical junction. This structure was followed superiorly to where it seemed to enter the peritoneum near the renal vessels. After opening the peritoneum, a small atrophic testicle was identified, and the tubular structure, which had become atretic, was noted to enter the right epididymis. The spermatic vessels were identified near the right renal vessels, and adequate mobilization to permit orchidopexy was decided impossible. A right orchiectomy with excision of the ectopic vas, right ureteral reimplantation, and testicular prosthesis implantation were
From the Division of Urology, Department of Surgery. Ohio State University, Columbus, OH, and the Section of Pediatric Urology, Division of Urology, Duke University Medical Center. Durham, NC. Date accepted: November 15.1988. Address reprint requests to Lowell R. King, MD, Division of Urology. Box 3707. Duke University Medical Center. Durham, NC 27710. o 1990 by W.B. Saunders Company. 0022-3468/90/2503-0016$03.00/0
335
NESBll-f AND KING
336
Fig 3. Cystogram shows reflux into blind ending stump and small ipsibteral hutch diverticulum.
Fig 1. Voiding cystourethrogram shows right-vesicoureteral reflux, international grade 3 of 6, and bilateral reflux into both right and left vasa defsrentia.
then accomplished. Follow-up IV urogram showed a normal right ureter with the absence of hydronephrosis. DISCUSSION
Although debate on the embryology and subsequent development of the distal Wolffian duct continues, one of the more popular theories is that of Mackie and
Fig 2. Voiding cystourethrogram shows international grade 3 of 6 left-vesicoureteral rellux with a small ipsilateral hutch diverticulum.
Stephens.’ At approximately 4 weeks of development, when the embryo is at the 4 mm stage, the cloaca, composed of endoderm, is still undivided. At this stage, a wedge of mesenchyme called the urorectal septum begins to grow caudally toward the cloaca1 membrane. Lateral end foldings also occur, fusing with the then completed urorectal septum to divide the cloaca into two parts: the rectum and upper anal canal dorsally, and the urogenital sinus ventrally. The urorectal septum fuses with the cloaca1 membrane, which is composed of endoderm from the cloaca and ectoderm from the anal pit, and divides it into a dorsal anal membrane and a ventral urogenital membrane. This area of fusion of the urorectal septum with the cloaca1 membrane persists as the perineal body. The urogenital sinus can then be subdivided into three parts: a cranial portion or vesicourethral canal, a middle pelvic portion, and a caudal phallic portion. The cranial portion of the urogenital sinus is continuous with the allantois. Endoderm from the urogenital sinus forms the epithelium of the bladder. The lamina propria and muscular layers, as well as serosa, develop from the splanchnic mesenchyme. As the bladder begins to enlarge and become distinct, the distal portions of the mesonephric duct become incorporated in the dorsal wall of the bladder and contribute to formation of the mucosa and superficial trigone of the bladder. This is then replaced by the endodermal epithelium of the urogenital sinus.4 Also at approximately 4 weeks, the ureteric bud, or metanephric diverticulum, is seen as a dorsal outpouching from the mesonephric duct, adjacent to the where it enters the mesonephric duct and the cloaca. As this duct grows dorsally and cranially, it extends into the metanephric blastema. Linkage occurs by approximately 6 weeks’ gestation. The mesonephric ducts then continue caudally to the level of the Muller’s hillock, which becomes verumontanum. By 7 weeks of develop-
ECTOPIC VAS
Fig 4. The ves takes its origin from the duct from a segment cranial to the possible ureteral bud sites. UGB. urogenital sinus; CMD, common meronephric duct: UB, ureteral bud: MB, metanephric blsstema; PVP, proximal ves precursor; UMD, upper mesonephric duct. (Reprinted with permission.‘)
ment, the mesonephric duct and the ureteral bud have separate openings into the urogenital sinus. Just prior to separation of these openings, there is a period when the ureter and distal portion of the terminal Wolffian duct have a collective stem called the common excretory duct. It is in this area and at this stage that Gibbons et al2 have focused, to expand Mackie and Stephen’s theory to explain ectopia of the vas deferens. They postulate the existence of a distinct zone on the Wolffian duct that is adjacent to the orthotopic ureteral budding zone (Fig 4). It lies cranially to the normal origin of the ureteral bud. If the ureteral bud takes its origin from this portion of the Wolffian duct, the ureteral orifice will come to lie in an ectopic caudal position on the trigone, after the theory of Mackie and Stevens. This joined portion of the Wolffian duct is also known as the common mesonephric duct and is the precursor of the trigone. Continuing cranially on the Wolfian duct, the proximal vas precursor normally lies immediately adjacent to the common mesonephric duct (Fig 4). This segment of the Wolffian duct will become the juxtaurethral vas deferens. The ejaculatory duct and seminal vesicle will eventually develop from this segment. According to Gibbons et al,’ the location of the proximal vas precursor between the upper mesonephric duct and the common mesonephric duct must have a “bipotential capability.” The implication is that the
337
proximal vas precursor segment may differentiate with either vasal or ureteral morphology. Several cases presented by Gibbons lended support to this theory.2 In these cases, the ectopic vas resembled a ureter histologically. The proximal vas precursor may become inserted abnormally in the ureter or bladder, if it is incorporated into the segment of the common mesonephric duct, which gives rise to the ureteral bud or trigone. It may also have ureteral morphology. It may impart vas-like morphology to the ureter if the ureteral bud originates from an abnormally proximal precursor. In case 1 in this report, the juxtaureteral vas deferens was found to have a transitional cell epithelial lining (Fig 5), whereas the more proximal portion seemed to be normal, giving some credence to the theory of bipotentiality in differentiation. One explanation for this type of anomaly in this theory is that encroachment of the proximal vas precursor, on the segment of the common mesonephric duct immediately adjacent to it, may alter the segment, confirming a bipotential capability for differentiation. Subsequently, this segment may develop either as a ureter or as a vas. In this instance, the common mesonephric duct then carried the insertion of the vas in the bladder (Fig 6). It is likely that the ureteric bud was abnormal in origin, so that the metanephric blastema was not intercepted at the appropriate level, leading to renal agenesis. A second possible explanation would be vasal conversion of the common mesonephric duct with agenesis of the left kidney, which is known to be associated with vas ectopia.
Fig 5. Histologic section from case 1 of the juxtaureteral ves deferens showing a mucosa composed of normal transitional cells.
NESEITT AND KING
BLADDER
URETER
Fig 6. Case 1, the vas has inserted ectopically into the bladder after being carried there by the common mesonephric duct. PVP, proximsl vas precursor.
The vas maintained normal histology in the case 2 (Fig 7), but inserted ectopically in the ureter. This may be explained by a further encroachment of the proximal vas precursor onto an even more caudal segment of the common mesonephric duct, so that the vas became connected to the ureteral bud itself. This then leads to the ectopically positioned vas entering the ureter. In this case, the testicle failed to descend as well, and a very high intraabdominal testicle was the result. The ultimate position of the ureter on the trigone is independent of vas development. Its position is dependent on the zone from which the ureteral bud originates. In case 1, the ureteral orifice was in an orthotopit location. Reflux commonly occurs into an ectopic vas deferens, but the vas does not necessarily have to be ectopically located to allow reflux. This is shown in case 1, in which vasal reflux was seen on the normal
Fig 7. The vas deferens has inserted ectopically in the ureter, which is explained by encroachment of the proximal vas precursor onto a more csudal segment of the common mewnephric duct. PVP, proximal vas precursor.
right side, and in case 2, in which the vas was also found to be in a normal position on the left side. The vasal reflux in both cases stopped after ureteral reimplantation. The normal vasa, which had allowed reflux in preoperative studies, were found to have stopped refluxing in postoperative studies. Although not present in either of the cases, epididymitis commonly occurs when vasal reflux is present. In these cases, extensive vasal reconstruction was not undertaken due to the presence of a normalappearing contralateral testis and ductal system. The success of such endeavors would seem unlikely in any case, due to the absence of seminal vesicle development that occurs with vas ectopia.
REFERENCES 1. Mackie GG, Stevens D: Duplex kidneys: A correlation of renal dysplasia with position of the ureteral orifice. J Urol 114~274-280, 1975 2. Gibbons MD, Chromie WJ, Duckett JW: Ectopicvas deferens. J Urol 120:597-604.1978
3. Schwarz R, Stephens FD: Persisting mesonephric duct. J Urol 120:592-596,1978 4. Gyllensten L: Contribution to embryology of the urinary bladder: Development of definitive relations between openings of the wolffian ducts and ureters. Acta Anat 7:305-344, 1949
of the Vas Deferens
By John A. Nesbitt II and Lowell R. King Columbus,
Ohio and Durham,
0 Ectopic location of the vas deferens is a rare congenital abnormality that has a spectrum of presentations. Such cases have been associated with anorectal anomalies. Knowledge of distal Wolffian duct embryology may help to explain the developmental steps invoked in these anomalies, as well as provide theories for the variations that may be encountered. Vas deferens development is reviewed, and two cases of vas ectopia are presented to illustrate and lend support to current theories of normal and abnormal vasal embryology. o 1gM by W.B. Saunders Company. INDEX WORDS: Vas deferens. ectopic location.
M
abnormalities ANY OF THE CONGENITAL of the lower urinary tract may be explained by an underlying defect in the proximal mesonephric duct or an abnormally proximal origin for the ureteric bud. Such anomalies would be found in the bladder, and involve the distal ureter and the vas deferens. Conversely, abnormalities seen consequent to altered distal ureteric bud formation are found in the kidney and upper ureter. As originally described by Mackie and Stephens,’ the theoretical embryological development of the distal Wolffian duct is essential in understanding many of the anomalies of the distal ureter, including ureteral ectopia. Later, Gibbons et al2 expanded this theory in an attempt to explain ectopia of the vas deferens. Ectopia of the vas deferens is a rare congenital anomality with multiple variations. The literature contains reports of about 25 cases since the first English description in 1898,3 with a spectrum of intercommunications between the vas and the urinary tract being described. Such cases are likely to be associated with anorectal developmental abnormalities, as well as ureteral ectopia and other distal Wolffian duct anomalies. The usual presentation of such patients is with epididymitis or urinary tract infection. Additionally, an ectopic vas may be discovered serendipitously upon routine examination of genitourinary or other congenital anomalies. Although scrotal pain may occur, many patients are asymptomatic. Two additional cases of vas ectopia are presented here and the embryology is subsequently discussed. CASE REPORTS Case I
J.H. was referred to the pediatric surgery service at Duke University Medical Center at 1 day of age with an imperforate anus. Radiographic studies showed high anorectal agenesis, with the large &al
of Pediatric Surgery,
Vol 25,
No 3 (March), 1990: pp 335-338
North Carolina
bowel terminating well above the puborectalis sling. A voiding cystourethrogram showed right vesicoureteral reflux, international grade 3 of 5, and bilateral reflux into both right and left vasa deferentia (Fig 1). The left ureter was not observed. After a sigmoid colostomy was performed, further evaluation of his urinary tract was accomplished. Ultrasound examination showed the right kidney to be of normal size with no evidence of hydronephrosis. No left kidney was identified. A radionuclide renal scan was obtained, demonstrating normal profusion and function of the right kidney, no renal tissue present in the left renal bal, and no ectopic functioning renal tissue. The patient underwent exploratory surgery. The left vas deferens was found to be continuous with the left ureteral segment, which then entered the bladder and formed an orthopically-placed ureteral orifice. The ureteral stump was ligated and the vas segment was excised to the level of the internal inguinal ring. The right ureter was reimplanted using the cross trigonal method of Cohen. Further extravesical exploration showed a vas deferens on the right that seemed to lie in a normal course and did not communicate with the ureter or bladder. It was suggested that the refhtx into the right vas on the preoperative voiding cystourethrogram had occurred because of an abnormal opening of the vas into the prostatic urethra. A follow-up cystogram at 4 months postoperatively showed no reflux into the right ureter or the right vaa deferens. Intravenous (IV) urography showed no obstruction of the right renal unit, and the child has remained free of infection. Case
2
M.M. was a Cyear-old boy referred to the pediatric urology service for evaluation of dysuria and an absent right testicle. Initial examination showed early reflux into the left vas deferens on filling cystogram and international grade 3/5 left veaicoureteral reflux (Fig 2). Additionally, there was determined to be a partially duplicated collecting system on the right, with a small right kidney, and reflux into a blind ending or obstructed distal ureter. The diagnosis of a ureteral diverticulum was also entertained (Fig 3). A small ipsilateral paraureteral diverticulum was identified as well. Cystoscopy showed a laterally displaced right ureteral or&e. During exploration, a tubular structure was noted to enter the right ureter approximately 4 cm above the ureteroveaical junction. This structure was followed superiorly to where it seemed to enter the peritoneum near the renal vessels. After opening the peritoneum, a small atrophic testicle was identified, and the tubular structure, which had become atretic, was noted to enter the right epididymis. The spermatic vessels were identified near the right renal vessels, and adequate mobilization to permit orchidopexy was decided impossible. A right orchiectomy with excision of the ectopic vas, right ureteral reimplantation, and testicular prosthesis implantation were
From the Division of Urology, Department of Surgery. Ohio State University, Columbus, OH, and the Section of Pediatric Urology, Division of Urology, Duke University Medical Center. Durham, NC. Date accepted: November 15.1988. Address reprint requests to Lowell R. King, MD, Division of Urology. Box 3707. Duke University Medical Center. Durham, NC 27710. o 1990 by W.B. Saunders Company. 0022-3468/90/2503-0016$03.00/0
335
NESBll-f AND KING
336
Fig 3. Cystogram shows reflux into blind ending stump and small ipsibteral hutch diverticulum.
Fig 1. Voiding cystourethrogram shows right-vesicoureteral reflux, international grade 3 of 6, and bilateral reflux into both right and left vasa defsrentia.
then accomplished. Follow-up IV urogram showed a normal right ureter with the absence of hydronephrosis. DISCUSSION
Although debate on the embryology and subsequent development of the distal Wolffian duct continues, one of the more popular theories is that of Mackie and
Fig 2. Voiding cystourethrogram shows international grade 3 of 6 left-vesicoureteral rellux with a small ipsilateral hutch diverticulum.
Stephens.’ At approximately 4 weeks of development, when the embryo is at the 4 mm stage, the cloaca, composed of endoderm, is still undivided. At this stage, a wedge of mesenchyme called the urorectal septum begins to grow caudally toward the cloaca1 membrane. Lateral end foldings also occur, fusing with the then completed urorectal septum to divide the cloaca into two parts: the rectum and upper anal canal dorsally, and the urogenital sinus ventrally. The urorectal septum fuses with the cloaca1 membrane, which is composed of endoderm from the cloaca and ectoderm from the anal pit, and divides it into a dorsal anal membrane and a ventral urogenital membrane. This area of fusion of the urorectal septum with the cloaca1 membrane persists as the perineal body. The urogenital sinus can then be subdivided into three parts: a cranial portion or vesicourethral canal, a middle pelvic portion, and a caudal phallic portion. The cranial portion of the urogenital sinus is continuous with the allantois. Endoderm from the urogenital sinus forms the epithelium of the bladder. The lamina propria and muscular layers, as well as serosa, develop from the splanchnic mesenchyme. As the bladder begins to enlarge and become distinct, the distal portions of the mesonephric duct become incorporated in the dorsal wall of the bladder and contribute to formation of the mucosa and superficial trigone of the bladder. This is then replaced by the endodermal epithelium of the urogenital sinus.4 Also at approximately 4 weeks, the ureteric bud, or metanephric diverticulum, is seen as a dorsal outpouching from the mesonephric duct, adjacent to the where it enters the mesonephric duct and the cloaca. As this duct grows dorsally and cranially, it extends into the metanephric blastema. Linkage occurs by approximately 6 weeks’ gestation. The mesonephric ducts then continue caudally to the level of the Muller’s hillock, which becomes verumontanum. By 7 weeks of develop-
ECTOPIC VAS
Fig 4. The ves takes its origin from the duct from a segment cranial to the possible ureteral bud sites. UGB. urogenital sinus; CMD, common meronephric duct: UB, ureteral bud: MB, metanephric blsstema; PVP, proximal ves precursor; UMD, upper mesonephric duct. (Reprinted with permission.‘)
ment, the mesonephric duct and the ureteral bud have separate openings into the urogenital sinus. Just prior to separation of these openings, there is a period when the ureter and distal portion of the terminal Wolffian duct have a collective stem called the common excretory duct. It is in this area and at this stage that Gibbons et al2 have focused, to expand Mackie and Stephen’s theory to explain ectopia of the vas deferens. They postulate the existence of a distinct zone on the Wolffian duct that is adjacent to the orthotopic ureteral budding zone (Fig 4). It lies cranially to the normal origin of the ureteral bud. If the ureteral bud takes its origin from this portion of the Wolffian duct, the ureteral orifice will come to lie in an ectopic caudal position on the trigone, after the theory of Mackie and Stevens. This joined portion of the Wolffian duct is also known as the common mesonephric duct and is the precursor of the trigone. Continuing cranially on the Wolfian duct, the proximal vas precursor normally lies immediately adjacent to the common mesonephric duct (Fig 4). This segment of the Wolffian duct will become the juxtaurethral vas deferens. The ejaculatory duct and seminal vesicle will eventually develop from this segment. According to Gibbons et al,’ the location of the proximal vas precursor between the upper mesonephric duct and the common mesonephric duct must have a “bipotential capability.” The implication is that the
337
proximal vas precursor segment may differentiate with either vasal or ureteral morphology. Several cases presented by Gibbons lended support to this theory.2 In these cases, the ectopic vas resembled a ureter histologically. The proximal vas precursor may become inserted abnormally in the ureter or bladder, if it is incorporated into the segment of the common mesonephric duct, which gives rise to the ureteral bud or trigone. It may also have ureteral morphology. It may impart vas-like morphology to the ureter if the ureteral bud originates from an abnormally proximal precursor. In case 1 in this report, the juxtaureteral vas deferens was found to have a transitional cell epithelial lining (Fig 5), whereas the more proximal portion seemed to be normal, giving some credence to the theory of bipotentiality in differentiation. One explanation for this type of anomaly in this theory is that encroachment of the proximal vas precursor, on the segment of the common mesonephric duct immediately adjacent to it, may alter the segment, confirming a bipotential capability for differentiation. Subsequently, this segment may develop either as a ureter or as a vas. In this instance, the common mesonephric duct then carried the insertion of the vas in the bladder (Fig 6). It is likely that the ureteric bud was abnormal in origin, so that the metanephric blastema was not intercepted at the appropriate level, leading to renal agenesis. A second possible explanation would be vasal conversion of the common mesonephric duct with agenesis of the left kidney, which is known to be associated with vas ectopia.
Fig 5. Histologic section from case 1 of the juxtaureteral ves deferens showing a mucosa composed of normal transitional cells.
NESEITT AND KING
BLADDER
URETER
Fig 6. Case 1, the vas has inserted ectopically into the bladder after being carried there by the common mesonephric duct. PVP, proximsl vas precursor.
The vas maintained normal histology in the case 2 (Fig 7), but inserted ectopically in the ureter. This may be explained by a further encroachment of the proximal vas precursor onto an even more caudal segment of the common mesonephric duct, so that the vas became connected to the ureteral bud itself. This then leads to the ectopically positioned vas entering the ureter. In this case, the testicle failed to descend as well, and a very high intraabdominal testicle was the result. The ultimate position of the ureter on the trigone is independent of vas development. Its position is dependent on the zone from which the ureteral bud originates. In case 1, the ureteral orifice was in an orthotopit location. Reflux commonly occurs into an ectopic vas deferens, but the vas does not necessarily have to be ectopically located to allow reflux. This is shown in case 1, in which vasal reflux was seen on the normal
Fig 7. The vas deferens has inserted ectopically in the ureter, which is explained by encroachment of the proximal vas precursor onto a more csudal segment of the common mewnephric duct. PVP, proximal vas precursor.
right side, and in case 2, in which the vas was also found to be in a normal position on the left side. The vasal reflux in both cases stopped after ureteral reimplantation. The normal vasa, which had allowed reflux in preoperative studies, were found to have stopped refluxing in postoperative studies. Although not present in either of the cases, epididymitis commonly occurs when vasal reflux is present. In these cases, extensive vasal reconstruction was not undertaken due to the presence of a normalappearing contralateral testis and ductal system. The success of such endeavors would seem unlikely in any case, due to the absence of seminal vesicle development that occurs with vas ectopia.
REFERENCES 1. Mackie GG, Stevens D: Duplex kidneys: A correlation of renal dysplasia with position of the ureteral orifice. J Urol 114~274-280, 1975 2. Gibbons MD, Chromie WJ, Duckett JW: Ectopicvas deferens. J Urol 120:597-604.1978
3. Schwarz R, Stephens FD: Persisting mesonephric duct. J Urol 120:592-596,1978 4. Gyllensten L: Contribution to embryology of the urinary bladder: Development of definitive relations between openings of the wolffian ducts and ureters. Acta Anat 7:305-344, 1949
