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The Histologic Effects of Dilation and Internal Urethrotomy on the Canine Urethra
Vol. 103, Feb. Printed in U.S.A.
THE JOURNAL OF UROLOGY
Copyright© 1970 by The Williams & Wilkins Co.
THE HISTOLOGIC EFFECTS OF DILATION AND INTERNAL URETHROTOMY ON THE CANINE URETHRA IAN M. THOMPSON
AND
JOHNSON J. BAKER
From the University of Missouri School of Medicine, Columbia, Missouri
Urethral dilation and internal urethrotomy are frequently done on children with urinary tract disorders. The results of such instrumentation as well as the rationale for it are not well understood. Our study was undertaken to evaluate the histologic effects of dilation and internal urethrotomy on the canine urethra, since the tissue response to such manipulation might roughly parallel that which would occur in the human. MATERIALS AND METHODS
Various studies were performed under barbiturate anesthesia on 16 adult, mongrel, female dogs weighing between 19.8 and 24.2 kg.: 1) urethral calibration, 2) urine culture and sensitivity studies, 3) excretory urograms (IVPs), 4) static cystograms and 5) voiding cystourethrograms. Five dogs were dilated with the straight Kollman dilator to 45F at weekly intervals for 6 weeks and then sacrificed at 1 to 6 weeks after the last dilation, subsequent to the repetition of the preoperative studies. Five dogs had internal urethrotomy performed to 38 or 45F with the Otis urethrotome and were sacrificed at similar intervals after calibration and radiologic study. One dog was dilated to 45F and sacrificed the next day and 1 dog had internal urethrotomy to 45F and was sacrificed 3 days later. Four control dogs had similar pre-instrumentation studies and were then sacrificed to evaluate the normal histology of the female urethra. The bladders were distended with formalin and the urethras were fixed to cardboard in a straight position. The vesicourethral outlets were divided into 4 equal portions and horizontal serial sections were made at similar points in each of the 4 segments. Hematoxylin and eosin, Masson's trichrome and elastic tissue stains were done on successive sections. Approximately 80 serial sections from each animal were studied. RESULTS
Normal controls. Four mongrel, female dogs, weighing between 18 and 24 kg., had urethral Accepted for publication March 17, 1969.
calibration following vaginal pin-back operations and a range of 16 to 24F was noted at the vesical neck. In 1 dog the meatus calibrated at 26F. IVPs, cystograms and voiding studies in these animals appeared normal. Urine cultures showed no growth. The histologic appearance of the sections from the 4 portions of the urethra and bladder outlet was quite similar in each animal. On horizontal section the arrangement of the tissue layers in the canine female urethra from the meatus toward the bladder outlet is as follows. In the meatal area there is an outer band of striated muscle which is quite thick anterior to the urethra and becomes continually thinner as it partially encircles the vagina (fig. 1, A). Fine longitudinal smooth muscle fibers course between this and the collagenous tissue around the urethral lumen. More proximally the anterior striated circular muscle begins to encircle the collagen core of the urethra itself (fig. 1, B). Longitudinal smooth muscle bundles perforate the collagen periurethral core and the entire urethra is surrounded by circular striated muscle (fig. 1, C). Further from the meatus the circular striated muscle blends into circular smooth muscle which first lies within the striated but more proximally replaces it around the thick collagen periurethral core. Then fine longitudinal smooth muscle bundles become visible within the thicker circular strands. In the mid-urethra, circular, smooth muscle predominates, with longitudinal, smooth muscle bundles most prominent anteriorly (fig. 1, D). In the proximal third of the urethra there is circular, smooth muscle around the collagen core and anterior longitudinal penetrating fibers in the outer collagen core. The outer longitudinal, smooth muscle becomes more and more prominent toward the bladder neck with the continuing presence of the circular smooth muscle layer adjacent to the collagen core which has fine longitudinal penetrating fibers at its periphery. Bladder muscle prolongations become more distinct anteriorly and posteriorly
168
HISTOLOGIC EFFECTS OF DILATION AND INTERNAL URETHROTOMY ON CANINE URETHRA
169
FIG.1
N on-histologic results of instrumentation Increase in Urethral Caliber (Fr. units) l\lean Range
Voiding Cystourethrography
--------
Internal urethrotomies (G dogs)
+6
+2-8
Urethra enlarged
---- -----1--Urethral
dihtions (6 dogs)
-1--5
+2-10
Urethra enlarged
IVP
Urine Cultures (Postop.)
---- ---Unchanged
Coliforms (I dog) Staph. aureus (2 dogs)
----l----
Unchanged Staph. a ureus (3 dogs)
as the vesical outlet is approached. Anteriorly and posteriorly placed longitudinal bundles lie outside the circular smooth muscle surrounding the collagen core (fig. 1, E). Longitudinal penetrating smooth muscle fibers are more prominent in the periphery of the collagen core especially anteriorly as the bladder outlet is reached. At the vesical outlet the thick, longitudinal anterior and posterior external layers of bladder muscle are noted lying superficial to the thick middle circular layer of smooth muscle (fig. 1, F). The disposition of these fibers is reminiscent of the arrangement in the human. Elastic tissue is condensed anterolaterally near the meatus but is distributed completely around the urethra and vagina superficial to the striated circular muscle. This pertains for the greater part of the distal urethra until a slimmer on the inner surface of the circular, smooth muscle of the urethra observed. There is fine elastin in the
core but aside from the distal condensation and the mid-urethral subcircular areas the amount of elastic tissue is not pronounced. At the vesical outlet and in the lower bladder elastin is predominantly deep to the larger circular and longitudinal smooth muscle bundles derived from the bladder wall, and superficial to the inner longitudinal penetrating smooth muscle. The elastin is oriented primarily horizontally. Results of dilation and i:nternal ,,,.,,,M·nt~,nm The non-histologic changes resulting from instrumentation are listed in the table. Urethral csJibers were substantially increased over the initial calibration in all dogs. Urine cultures initially showed no growth in all dogs. Staphylococcus aureus was cultured in 3 dogs after dilation while 1 urethrotomy dog had a coliform organism on culture and two others had Staphylococcus aureus. IVPs were normal before and after instrumentation. Voiding studies demonstrated definite enlargement of the urethras of both the dilation and urethrotomy dogs in comparison with their preoperative films and those of the controls (fig. 2), HIS'l'OLOGIC CHANGES
The predominant histologic effects of urethral dilation were 1) general distraction of all circular muscle, striated and smooth, with displacement and attenuation of longitudinal bundles (fig. 2) looser articulation (fig, 4, and distraction of all tissues around the urethral lumen; 3) inent vacuolization and hemorrhage 4) areas of core collagen scar which stage of condensation
170
THOMPSON AND BAKER
FIG. 2
Fm. 4 FIG. 3
The effects of internal urethrotomy were: 1) shearing division of circular muscle bundles (fig. 6); 2) blending of core collagen into areas of muscle disruption (fig. 7, A) and in a number of sections collagen condensation stages of response
to injury; 3) isolated sections (fig. 7, B) in which calcification occurred in the area of muscle disruption which was filled by collagen (fig. 8, A); 4) vacuolization, hemorrhage and distraction of the periluminal core were apparent but generally less pronounced than in the dilated urethras (fig. 8, B).
HISTOLOGIC EFFECTS OF DILATION AND INTERNAL URETHROTO:\fY ON CANINE URETHRA
171
The dogs sacrificed at 24 and 72 hours after dilation and internal urethrotomy demonstrated slightly more submucosal hemorrhage, but otherwise the histologic response was similar to the animals sacrificed at longer intervals following instrumentation. No differences were noted in the
histologic appearance of urethras dilated to either 38 or 45F. No consistent changes in the amount, position or disposition of elastic tissue were discernible following dilation or urethrotomy.
FIG. 5
FIG. 6
Fm. 7
172
THOMPSON AND BAKER
Fm. 8 DISCUSSION
The general impression that the most marked distraction in both the dilation and urethrotomy dogs occurred predominantly in the collagen core was confirmed at each comparison with the normal material. The hemorrhage which was scattered through the core with submucosal condensations was accentuated in dogs sacrificed soon after instrumentation but was a distinctive feature in both series irrespective of time of sacrifice. A clear-cut difference between dilation and urethrotomy was seen in the attenuation of circular striated and smooth muscles, following dilation, and the sheared disruption of the musculature in the urethrotomy animals. The earliest and most pronounced changes in the muscle and subjacent submucosal collagen core, leading to deposition of firm scar and calcification, occurred in the urethras subjected to urethrotomy. However, in many areas of the submucosal core in the dilation series, condensation of collagen was characteristic
of the tissue reaction seen prior to calcification and bone formation. The radiographic increase in outlet size after dilation and urethrotomy was observed on calibration and was also apparent histologically. Although dilation was performed 6 times in each dog and urethrotomy only once, the tissue reaction was equally noticeable and in many ways similar in both series. The degree to which dilation and urethrotomy were carried in these animals does not seem unreasonable in view of the fact that pre-instrumentation caliber closely approximated that of the adult human urethra. CONCLUSIONS
It is evident from this study that both urethral dilation and urethrotomy can achieve larger urethras and that this can be documented by calibration, x-ray examination and histologic section. Urethrotomy produces division of circular
HISTOLOGIC EFFECTS OF DILATION AND INTERNAL URETHROTOMY 0)1 CANINE URETHRA
muscle which appears to heal by fibrosis at the site of rupture, while dilation produces muscle stretching or distraction without gross evidence of scar formation in the muscle layer. Dilation and urethrotomy produce a substantial reaction in the core area with a noticeably greater disruption and fibrous condensation attributable to dilation. Yvhether these histologic findings bear any to ,vhat may clinically or
173
structurally following dilation or urethrotomy in the human cannot be assumed, particularly since this short-term experiment provides no infonnation as to the eventual resolution of these early changes. However, it is possible that the relatively acute effects observed in these normal animals might be comparable to those occurring in the normal human child after urethral dilation internal urethrotomy.
THE JOURNAL OF UROLOGY
Copyright© 1970 by The Williams & Wilkins Co.
THE HISTOLOGIC EFFECTS OF DILATION AND INTERNAL URETHROTOMY ON THE CANINE URETHRA IAN M. THOMPSON
AND
JOHNSON J. BAKER
From the University of Missouri School of Medicine, Columbia, Missouri
Urethral dilation and internal urethrotomy are frequently done on children with urinary tract disorders. The results of such instrumentation as well as the rationale for it are not well understood. Our study was undertaken to evaluate the histologic effects of dilation and internal urethrotomy on the canine urethra, since the tissue response to such manipulation might roughly parallel that which would occur in the human. MATERIALS AND METHODS
Various studies were performed under barbiturate anesthesia on 16 adult, mongrel, female dogs weighing between 19.8 and 24.2 kg.: 1) urethral calibration, 2) urine culture and sensitivity studies, 3) excretory urograms (IVPs), 4) static cystograms and 5) voiding cystourethrograms. Five dogs were dilated with the straight Kollman dilator to 45F at weekly intervals for 6 weeks and then sacrificed at 1 to 6 weeks after the last dilation, subsequent to the repetition of the preoperative studies. Five dogs had internal urethrotomy performed to 38 or 45F with the Otis urethrotome and were sacrificed at similar intervals after calibration and radiologic study. One dog was dilated to 45F and sacrificed the next day and 1 dog had internal urethrotomy to 45F and was sacrificed 3 days later. Four control dogs had similar pre-instrumentation studies and were then sacrificed to evaluate the normal histology of the female urethra. The bladders were distended with formalin and the urethras were fixed to cardboard in a straight position. The vesicourethral outlets were divided into 4 equal portions and horizontal serial sections were made at similar points in each of the 4 segments. Hematoxylin and eosin, Masson's trichrome and elastic tissue stains were done on successive sections. Approximately 80 serial sections from each animal were studied. RESULTS
Normal controls. Four mongrel, female dogs, weighing between 18 and 24 kg., had urethral Accepted for publication March 17, 1969.
calibration following vaginal pin-back operations and a range of 16 to 24F was noted at the vesical neck. In 1 dog the meatus calibrated at 26F. IVPs, cystograms and voiding studies in these animals appeared normal. Urine cultures showed no growth. The histologic appearance of the sections from the 4 portions of the urethra and bladder outlet was quite similar in each animal. On horizontal section the arrangement of the tissue layers in the canine female urethra from the meatus toward the bladder outlet is as follows. In the meatal area there is an outer band of striated muscle which is quite thick anterior to the urethra and becomes continually thinner as it partially encircles the vagina (fig. 1, A). Fine longitudinal smooth muscle fibers course between this and the collagenous tissue around the urethral lumen. More proximally the anterior striated circular muscle begins to encircle the collagen core of the urethra itself (fig. 1, B). Longitudinal smooth muscle bundles perforate the collagen periurethral core and the entire urethra is surrounded by circular striated muscle (fig. 1, C). Further from the meatus the circular striated muscle blends into circular smooth muscle which first lies within the striated but more proximally replaces it around the thick collagen periurethral core. Then fine longitudinal smooth muscle bundles become visible within the thicker circular strands. In the mid-urethra, circular, smooth muscle predominates, with longitudinal, smooth muscle bundles most prominent anteriorly (fig. 1, D). In the proximal third of the urethra there is circular, smooth muscle around the collagen core and anterior longitudinal penetrating fibers in the outer collagen core. The outer longitudinal, smooth muscle becomes more and more prominent toward the bladder neck with the continuing presence of the circular smooth muscle layer adjacent to the collagen core which has fine longitudinal penetrating fibers at its periphery. Bladder muscle prolongations become more distinct anteriorly and posteriorly
168
HISTOLOGIC EFFECTS OF DILATION AND INTERNAL URETHROTOMY ON CANINE URETHRA
169
FIG.1
N on-histologic results of instrumentation Increase in Urethral Caliber (Fr. units) l\lean Range
Voiding Cystourethrography
--------
Internal urethrotomies (G dogs)
+6
+2-8
Urethra enlarged
---- -----1--Urethral
dihtions (6 dogs)
-1--5
+2-10
Urethra enlarged
IVP
Urine Cultures (Postop.)
---- ---Unchanged
Coliforms (I dog) Staph. aureus (2 dogs)
----l----
Unchanged Staph. a ureus (3 dogs)
as the vesical outlet is approached. Anteriorly and posteriorly placed longitudinal bundles lie outside the circular smooth muscle surrounding the collagen core (fig. 1, E). Longitudinal penetrating smooth muscle fibers are more prominent in the periphery of the collagen core especially anteriorly as the bladder outlet is reached. At the vesical outlet the thick, longitudinal anterior and posterior external layers of bladder muscle are noted lying superficial to the thick middle circular layer of smooth muscle (fig. 1, F). The disposition of these fibers is reminiscent of the arrangement in the human. Elastic tissue is condensed anterolaterally near the meatus but is distributed completely around the urethra and vagina superficial to the striated circular muscle. This pertains for the greater part of the distal urethra until a slimmer on the inner surface of the circular, smooth muscle of the urethra observed. There is fine elastin in the
core but aside from the distal condensation and the mid-urethral subcircular areas the amount of elastic tissue is not pronounced. At the vesical outlet and in the lower bladder elastin is predominantly deep to the larger circular and longitudinal smooth muscle bundles derived from the bladder wall, and superficial to the inner longitudinal penetrating smooth muscle. The elastin is oriented primarily horizontally. Results of dilation and i:nternal ,,,.,,,M·nt~,nm The non-histologic changes resulting from instrumentation are listed in the table. Urethral csJibers were substantially increased over the initial calibration in all dogs. Urine cultures initially showed no growth in all dogs. Staphylococcus aureus was cultured in 3 dogs after dilation while 1 urethrotomy dog had a coliform organism on culture and two others had Staphylococcus aureus. IVPs were normal before and after instrumentation. Voiding studies demonstrated definite enlargement of the urethras of both the dilation and urethrotomy dogs in comparison with their preoperative films and those of the controls (fig. 2), HIS'l'OLOGIC CHANGES
The predominant histologic effects of urethral dilation were 1) general distraction of all circular muscle, striated and smooth, with displacement and attenuation of longitudinal bundles (fig. 2) looser articulation (fig, 4, and distraction of all tissues around the urethral lumen; 3) inent vacuolization and hemorrhage 4) areas of core collagen scar which stage of condensation
170
THOMPSON AND BAKER
FIG. 2
Fm. 4 FIG. 3
The effects of internal urethrotomy were: 1) shearing division of circular muscle bundles (fig. 6); 2) blending of core collagen into areas of muscle disruption (fig. 7, A) and in a number of sections collagen condensation stages of response
to injury; 3) isolated sections (fig. 7, B) in which calcification occurred in the area of muscle disruption which was filled by collagen (fig. 8, A); 4) vacuolization, hemorrhage and distraction of the periluminal core were apparent but generally less pronounced than in the dilated urethras (fig. 8, B).
HISTOLOGIC EFFECTS OF DILATION AND INTERNAL URETHROTO:\fY ON CANINE URETHRA
171
The dogs sacrificed at 24 and 72 hours after dilation and internal urethrotomy demonstrated slightly more submucosal hemorrhage, but otherwise the histologic response was similar to the animals sacrificed at longer intervals following instrumentation. No differences were noted in the
histologic appearance of urethras dilated to either 38 or 45F. No consistent changes in the amount, position or disposition of elastic tissue were discernible following dilation or urethrotomy.
FIG. 5
FIG. 6
Fm. 7
172
THOMPSON AND BAKER
Fm. 8 DISCUSSION
The general impression that the most marked distraction in both the dilation and urethrotomy dogs occurred predominantly in the collagen core was confirmed at each comparison with the normal material. The hemorrhage which was scattered through the core with submucosal condensations was accentuated in dogs sacrificed soon after instrumentation but was a distinctive feature in both series irrespective of time of sacrifice. A clear-cut difference between dilation and urethrotomy was seen in the attenuation of circular striated and smooth muscles, following dilation, and the sheared disruption of the musculature in the urethrotomy animals. The earliest and most pronounced changes in the muscle and subjacent submucosal collagen core, leading to deposition of firm scar and calcification, occurred in the urethras subjected to urethrotomy. However, in many areas of the submucosal core in the dilation series, condensation of collagen was characteristic
of the tissue reaction seen prior to calcification and bone formation. The radiographic increase in outlet size after dilation and urethrotomy was observed on calibration and was also apparent histologically. Although dilation was performed 6 times in each dog and urethrotomy only once, the tissue reaction was equally noticeable and in many ways similar in both series. The degree to which dilation and urethrotomy were carried in these animals does not seem unreasonable in view of the fact that pre-instrumentation caliber closely approximated that of the adult human urethra. CONCLUSIONS
It is evident from this study that both urethral dilation and urethrotomy can achieve larger urethras and that this can be documented by calibration, x-ray examination and histologic section. Urethrotomy produces division of circular
HISTOLOGIC EFFECTS OF DILATION AND INTERNAL URETHROTOMY 0)1 CANINE URETHRA
muscle which appears to heal by fibrosis at the site of rupture, while dilation produces muscle stretching or distraction without gross evidence of scar formation in the muscle layer. Dilation and urethrotomy produce a substantial reaction in the core area with a noticeably greater disruption and fibrous condensation attributable to dilation. Yvhether these histologic findings bear any to ,vhat may clinically or
173
structurally following dilation or urethrotomy in the human cannot be assumed, particularly since this short-term experiment provides no infonnation as to the eventual resolution of these early changes. However, it is possible that the relatively acute effects observed in these normal animals might be comparable to those occurring in the normal human child after urethral dilation internal urethrotomy.