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Urethral Reconstruction Using the Carbon Dioxide Laser: An Experimental Evaluation
0022 -0347 /89 /!._ 424-1139$02.0C /0
Vol. l
THE JOURNAL OF URSLOGY
Copyright© 198S by AIAERlCAN Urt,OLOG!CAL ASSOCIATION, INC"
US[NG THE CARBON DIOXIDE EXPERIMEI\JTAL EVALUATION GEORGES.
DIX P. POPPAS, CHARLES J. DEVINE, STEVEN M. SCHLOSSBERG*
JR. AND
From the Department of Urology, Eastern Virginia Medical School, Norfolk, Virginia
ABSTRACT
In an effort to test the efficacy of the carbon dioxide laser in urethral reconstruction, patch graft urethroplasty was carried out comparing laser repair to microsurgical repair. The male Sprague Dawley rat was used as the model. An oval defect was created in the ventral urethra in 65 animals and repaired with a full thickness preputial skin graft using conventional microsurgical repair, laser assisted microsurgical repair, or laser repair with a protein solder. The success rate, defined as the number of animals surviving without complications at the end of 21 days, was 50, 20, and 65% respectively. In conclusion, laser assisted repair using the protein solder was significantly better than microsurgical repair (p <0.05). (J. Urol., 142: 1139-1141, 1989) Successful primary repair of hypospadias has continued to challenge the ability of the reconstructive surgeon, as attested to by the number of methods in use today. 1 • 2 In an attempt to decrease the postoperative urethrocutaneous fistula rate, Gilbert et al. 3 employed microsurgical techniques in the repair of distal hypospadias. Their efforts resulted in a decrease in the fistula rate from 10 to 15% to 6.5%. However, microsurgical techniques are time consuming and, when applied to proximal hypospadias, significantly increase the operating time and hence the cost. Serure 4 successfully used the carbon dioxide laser in vascular anastomosis. In addition to being significantly faster than standard microsutu:re anastomosis, the laser was found to produce less foreign body reaction and hence a 100% patency rate. With this in view, Poppas et al.,5 applied the CO2 laser to urethral reconstruction. A partial transection of the ventral urethra of the rat was repaired using conventional microsurgery and laser assisted microsurgery with and without a protein solder. This initial expe:rin1e11t demonstrated the ability to use the CO 2 laser with and without a solder in urethral surgery. In most hypospadias surgery, skin is used to augment and elongate the deficient urethra. 1 ' 2 Therefore in a new set of experiments, the laser wa_s used to no,,+r>.-rn a demonstrates the cs::
abdominal wall using two 8-0 nylon sutures. The urethra was stented using a 22 gauge Gelco catheter and secured to the glans penis. A one centimeter ventral midline skin incision was made just proximal to the coronal sulcus (fig. lB). The spongiosum was identified and sharply dissected off the corpora, mobilizing it to a length of one cm. A 2-0 silk tie was placed proximally and distally on the mobilized urethra to c~ntrol bieeding once the spongiosum was incised. A bloodless field is critical in achieving a laser weld. An oval defect measuring 2 mm. X 1 mm. was made in the ventral urethra (fig. lC). Hemostasis from the spongiosum was achieved by the application of thrombin crystals to the edges of the defect (Thrombstat Bovine origin, Parker Davis). A full thickness preputial skin graft was harvested, trimmed, and placed over the defect. The donor site was closed using a continuous 10-0 nylon suture. Repair of the defect was performed using one of five paradigms. In the first control group, the patch was not sutured but placed over the defect (fig. 2-1) and the overlying soft tissue and skin closed using 8-0 nylon sutures. In the second control group, which formed a basis for the laser repair, the defect was closed using four 10-0 nylon sutures placed in the four quadrants (fig. 2-2). The third group was repaired using conven-
MATERIALS AND METHODS
The experiment was performed on aduit male Sprague Dawley rats (450 to 600 grams) using a Zeiss-OPMI-6 operating microscope for all procedures (10-15X). Laser welding was performed using a LaserSonics carbon dioxide milliwatt laser (Cavitron model 870A) with a spot size of 600 micrometers and a power setting of 120 milliwatts. The laser energy was applied using a mechanical shutter pulse at 50 msec. duration. The animals were anesthetized with intraperitoneal nembutal (five mg. per 100 grams) and perioperative antibiotics (penicillin 200 units per 100 grams) were administered subcutaneously. The genital and abdominal hair was shaved, and the phallus extended and anchored to the anterior abdominal wall using an 8-0 nylon suture placed through the prepuce (fig. lA). The preputial skin was also advanced and sutured to the ventral Accepted for publication May 9, 1989. * Requests for reprints: 400 West Brambleton Ave., Suite 400, Norfolk, VA 23510. 1139
FIG. 1. Exposure of urethra.
1140
GANESAN AND ASSOCIATES TABLE 1.
Group 1 2 3 4 5
4.
(Control) (4 Suture-Control) (12 Suture) (Suture-Laser) (Suture-Laser-Solder)
Results Complications
No.in Group
Obstruction
Fistulae
5 10 20 10 20
4 6 3 4 4
1 4 7
4 3
Success 0% 0% 50% 20% 65%
FIG. 2. Five methods for repair.
tional microsurgical techniques with twelve 10-0 nylon sutures holding the graft circumferentially (fig. 2-3). In the fourth group the graft was secured to the urethra in four quadrants. The laser was applied to weld the skin edge to that of the cut urethra (fig. 2-4). In the fifth group, an identical laser repair was performed as in Group 4 with the addition of a protein solder applied to the edges prior to welding (fig. 2-5). The protein solder consisted of a suspension of 500 milligrams egg albumin in 0.5 cc. normal saline centrifuged at 3600 RPM for three minutes. A third control group, using the laser alone, was not included since we could not get the patch of preputial skin to hold the urethra without the addition of suture/or solder. Postoperatively the animals were returned to their suspension cages and maintained on antibiotics (tetracycline) in their drinking water. The urethral stent was removed under anesthesia by 48 hours if not already out. At three weeks postoperatively, the animals were anesthetized and the repair examined using a retrograde injection of Methylene Blue into the urethra to test for the presence of a urethrocutaneous fistula. The animals were then sacrificed with an overdose of barbiturates and an autopsy performed to examine for obstructive uropathy. RESULTS
Success was defined as the number of animals surviving three weeks without complications. Two patterns of complications were noted. The first was massive urinary extravasation and infection in the perinea! tissues occurring within nine days from surgery. In this group, the urethra at the site of repair was noted to be obstructed with dilatation of the urinary tract and urethra proximal to the repair. The second complication observed was urethrocutaneous fistula. These animals survived 21 days following surgery. At autopsy they had a patent urethra with normal bladder and upper tracts. Our results are presented in table 1. In the first control group (Group 1) where the patch was placed over the defect, all animals developed complications. In the second control group (Group II), the four suture model, all repairs failed. The group of animals repaired using the laser alone (Group IV) showed poor results; only 20% survived without complications. Group III (fig. 3) animals which were repaired using microsuture alone yielded a 50% success rate. A 65% success rate was observed in Group V (fig. 4) where a protein solder was added prior to the laser weld. The results were analyzed using a oneway analysis of variance, comparing the rate of complications among the various models. This analysis was significant (p <.01), and a Duncan's mean comparison test indicated that the 12 suture model and the suture-laser-solder model had significantly lower rates of complication than the other models. Based on these results, the 12 suture model and the suture-laser-solder model were subjected to a Student's t test to examine differences in their
FIG. 3. Photograph taken under operating microscope of 12 suture model. Note even distribution of 12 microstructures securing graft to urethra.
rate of complication. The t test was also significant (p <.05), showing the suture-laser-solder model to have the lowest rate of complications, overall. DISCUSSION
This study together with the earlier experiment5 from the same institution pioneered the application of laser technology in urethral reconstruction. The carbon dioxide laser emissions, unlike other lasers, is heavily absorbed by water. Cells are largely composed of water, and hence 98% of the laser energy is absorbed in approximately 0.17 mm. of tissue.7 This makes the CO2 laser ideal for welding, thus its application in our experiments. Our earlier study. 5 to determine the efficacy of the laser in urethral reconstruction, gave overwhelmingly successful results. However, the experiment was designed to weld urethra to urethra. This experiment was intended to test the above results in a more clinical setting. Complex hypospadias surgery involves the use of skin or other epithelial lined flaps or grafts
URETHRAL RECONSTRUCTION USING CARBON DIOXIDE LASER
1141
ard fashion to obtain consistent results with the weld. We attribute our success with the laser and solder to the special effects of the protein in the egg albumin which denatures upon application of the laser energy and behaves in a fashion analogous to solder used to join metallic parts with the application of heat. In contrast, when trying to weld the graft to the urethra without solder, too much heat is transferred directly to the graft. Therefore, dessication and destruction of the graft occur resulting in poor healing. Many questions still need to be answered before this technique can be transferred to a clinical setting. Experiments have been designed and are under way: to determine the ideal laser parameters which may be applied to urethral tissue to effect the best weld with the least amount of tissue destruction, to determine the exact function of the protein solder, and the sequence of healing which occurs when laser energy is applied to urethral tissue. Acknowledgments. We are indebted to LaserSonics Division of Cooper Corporation for the use of their CO2 milliwatt laser, to Brian Maddox of Ethicon for supplying microsutures, to Christine Philput, Research and Statistical Consultant at Eastern Virginia Medical School, for the statistical analysis of the data, and to the Microsurgical Research Center of Eastern Virginia Medical School for the use of their facilities. REFERENCES 1. Duckett, J. W.: Hypospadias. In: Campbell's Urology, Fifth Edition,
2. 3. FIG. 4. Intraoperative picture of suture-laser-solder model. Note absence of carbonization along edges where laser weld has occurred.
in the form of a patch or tube to extend the urethral opening to the tip of the penis. 1• 2 In this situation, we found that application of the laser with the protein solder gave superior results that were statistically significant when compared to the use of microsuture alone. Further, this modality of repair reduced operating time by 30%. The use of the laser alone yielded a success rate of only 20%, much lower than with microsuture alone. The egg albumin used in the solder was prepared in a stand-
4.
5. 6.
7.
volume 2. Edited by P. C. Walsh, R. E. Gittes, A. D. Perlmutter and T. A. Stamey. Philadelphia: W.B. Saunders Company, pp. 1969-1999, 1986. Belman, A. B.: Urethra. In: Clinical Pediatric Urology, Second Edition, volume 2. Edited by P. P. Kelalis, L. R. King and A. B. Belman. Philadelphia: W.B. Saunders, pp. 751-792, 1985. Gilbert, D. A., Devine, C. J. and Winslow, B. H.: Microsurgical hypospadias repair. Plast. Reconstr. Surg., 77: 460, 1986. Serure, A., Withers, E., Thomsen, S. and Morris, J.: Comparison of carbon dioxide laser-assisted microvascular anastomosis and conventional microvascular sutured anastomosis. Surg. Forum, 34: 635, 1983. Poppas, D. P., Schlossberg, S. M., Richmond, I. L., Gilbert, D. A. and Devine, C. J.: Laser welding in urethral surgery: improved results with a protein solder. J. Urol., 139: 415, 1988. Ganesan, G. S., Schlossberg, S. M., Poppas, D., Richmond and Devine, C. J., Jr.: Urethral reconstruction using the CO 2 laseran experimental evaluation. Abstract #684, J. Urol. 139: 333A, 1988. Fuller, T. A.: Fundamentals of lasers in surgery and medicine. In: Surgical Application of Lasers. Edited by John A. Dixon. Chicago: Year Book Medical Publishers, pp. 16-33, 1987.
Vol. l
THE JOURNAL OF URSLOGY
Copyright© 198S by AIAERlCAN Urt,OLOG!CAL ASSOCIATION, INC"
US[NG THE CARBON DIOXIDE EXPERIMEI\JTAL EVALUATION GEORGES.
DIX P. POPPAS, CHARLES J. DEVINE, STEVEN M. SCHLOSSBERG*
JR. AND
From the Department of Urology, Eastern Virginia Medical School, Norfolk, Virginia
ABSTRACT
In an effort to test the efficacy of the carbon dioxide laser in urethral reconstruction, patch graft urethroplasty was carried out comparing laser repair to microsurgical repair. The male Sprague Dawley rat was used as the model. An oval defect was created in the ventral urethra in 65 animals and repaired with a full thickness preputial skin graft using conventional microsurgical repair, laser assisted microsurgical repair, or laser repair with a protein solder. The success rate, defined as the number of animals surviving without complications at the end of 21 days, was 50, 20, and 65% respectively. In conclusion, laser assisted repair using the protein solder was significantly better than microsurgical repair (p <0.05). (J. Urol., 142: 1139-1141, 1989) Successful primary repair of hypospadias has continued to challenge the ability of the reconstructive surgeon, as attested to by the number of methods in use today. 1 • 2 In an attempt to decrease the postoperative urethrocutaneous fistula rate, Gilbert et al. 3 employed microsurgical techniques in the repair of distal hypospadias. Their efforts resulted in a decrease in the fistula rate from 10 to 15% to 6.5%. However, microsurgical techniques are time consuming and, when applied to proximal hypospadias, significantly increase the operating time and hence the cost. Serure 4 successfully used the carbon dioxide laser in vascular anastomosis. In addition to being significantly faster than standard microsutu:re anastomosis, the laser was found to produce less foreign body reaction and hence a 100% patency rate. With this in view, Poppas et al.,5 applied the CO2 laser to urethral reconstruction. A partial transection of the ventral urethra of the rat was repaired using conventional microsurgery and laser assisted microsurgery with and without a protein solder. This initial expe:rin1e11t demonstrated the ability to use the CO 2 laser with and without a solder in urethral surgery. In most hypospadias surgery, skin is used to augment and elongate the deficient urethra. 1 ' 2 Therefore in a new set of experiments, the laser wa_s used to no,,+r>.-rn a demonstrates the cs::
abdominal wall using two 8-0 nylon sutures. The urethra was stented using a 22 gauge Gelco catheter and secured to the glans penis. A one centimeter ventral midline skin incision was made just proximal to the coronal sulcus (fig. lB). The spongiosum was identified and sharply dissected off the corpora, mobilizing it to a length of one cm. A 2-0 silk tie was placed proximally and distally on the mobilized urethra to c~ntrol bieeding once the spongiosum was incised. A bloodless field is critical in achieving a laser weld. An oval defect measuring 2 mm. X 1 mm. was made in the ventral urethra (fig. lC). Hemostasis from the spongiosum was achieved by the application of thrombin crystals to the edges of the defect (Thrombstat Bovine origin, Parker Davis). A full thickness preputial skin graft was harvested, trimmed, and placed over the defect. The donor site was closed using a continuous 10-0 nylon suture. Repair of the defect was performed using one of five paradigms. In the first control group, the patch was not sutured but placed over the defect (fig. 2-1) and the overlying soft tissue and skin closed using 8-0 nylon sutures. In the second control group, which formed a basis for the laser repair, the defect was closed using four 10-0 nylon sutures placed in the four quadrants (fig. 2-2). The third group was repaired using conven-
MATERIALS AND METHODS
The experiment was performed on aduit male Sprague Dawley rats (450 to 600 grams) using a Zeiss-OPMI-6 operating microscope for all procedures (10-15X). Laser welding was performed using a LaserSonics carbon dioxide milliwatt laser (Cavitron model 870A) with a spot size of 600 micrometers and a power setting of 120 milliwatts. The laser energy was applied using a mechanical shutter pulse at 50 msec. duration. The animals were anesthetized with intraperitoneal nembutal (five mg. per 100 grams) and perioperative antibiotics (penicillin 200 units per 100 grams) were administered subcutaneously. The genital and abdominal hair was shaved, and the phallus extended and anchored to the anterior abdominal wall using an 8-0 nylon suture placed through the prepuce (fig. lA). The preputial skin was also advanced and sutured to the ventral Accepted for publication May 9, 1989. * Requests for reprints: 400 West Brambleton Ave., Suite 400, Norfolk, VA 23510. 1139
FIG. 1. Exposure of urethra.
1140
GANESAN AND ASSOCIATES TABLE 1.
Group 1 2 3 4 5
4.
(Control) (4 Suture-Control) (12 Suture) (Suture-Laser) (Suture-Laser-Solder)
Results Complications
No.in Group
Obstruction
Fistulae
5 10 20 10 20
4 6 3 4 4
1 4 7
4 3
Success 0% 0% 50% 20% 65%
FIG. 2. Five methods for repair.
tional microsurgical techniques with twelve 10-0 nylon sutures holding the graft circumferentially (fig. 2-3). In the fourth group the graft was secured to the urethra in four quadrants. The laser was applied to weld the skin edge to that of the cut urethra (fig. 2-4). In the fifth group, an identical laser repair was performed as in Group 4 with the addition of a protein solder applied to the edges prior to welding (fig. 2-5). The protein solder consisted of a suspension of 500 milligrams egg albumin in 0.5 cc. normal saline centrifuged at 3600 RPM for three minutes. A third control group, using the laser alone, was not included since we could not get the patch of preputial skin to hold the urethra without the addition of suture/or solder. Postoperatively the animals were returned to their suspension cages and maintained on antibiotics (tetracycline) in their drinking water. The urethral stent was removed under anesthesia by 48 hours if not already out. At three weeks postoperatively, the animals were anesthetized and the repair examined using a retrograde injection of Methylene Blue into the urethra to test for the presence of a urethrocutaneous fistula. The animals were then sacrificed with an overdose of barbiturates and an autopsy performed to examine for obstructive uropathy. RESULTS
Success was defined as the number of animals surviving three weeks without complications. Two patterns of complications were noted. The first was massive urinary extravasation and infection in the perinea! tissues occurring within nine days from surgery. In this group, the urethra at the site of repair was noted to be obstructed with dilatation of the urinary tract and urethra proximal to the repair. The second complication observed was urethrocutaneous fistula. These animals survived 21 days following surgery. At autopsy they had a patent urethra with normal bladder and upper tracts. Our results are presented in table 1. In the first control group (Group 1) where the patch was placed over the defect, all animals developed complications. In the second control group (Group II), the four suture model, all repairs failed. The group of animals repaired using the laser alone (Group IV) showed poor results; only 20% survived without complications. Group III (fig. 3) animals which were repaired using microsuture alone yielded a 50% success rate. A 65% success rate was observed in Group V (fig. 4) where a protein solder was added prior to the laser weld. The results were analyzed using a oneway analysis of variance, comparing the rate of complications among the various models. This analysis was significant (p <.01), and a Duncan's mean comparison test indicated that the 12 suture model and the suture-laser-solder model had significantly lower rates of complication than the other models. Based on these results, the 12 suture model and the suture-laser-solder model were subjected to a Student's t test to examine differences in their
FIG. 3. Photograph taken under operating microscope of 12 suture model. Note even distribution of 12 microstructures securing graft to urethra.
rate of complication. The t test was also significant (p <.05), showing the suture-laser-solder model to have the lowest rate of complications, overall. DISCUSSION
This study together with the earlier experiment5 from the same institution pioneered the application of laser technology in urethral reconstruction. The carbon dioxide laser emissions, unlike other lasers, is heavily absorbed by water. Cells are largely composed of water, and hence 98% of the laser energy is absorbed in approximately 0.17 mm. of tissue.7 This makes the CO2 laser ideal for welding, thus its application in our experiments. Our earlier study. 5 to determine the efficacy of the laser in urethral reconstruction, gave overwhelmingly successful results. However, the experiment was designed to weld urethra to urethra. This experiment was intended to test the above results in a more clinical setting. Complex hypospadias surgery involves the use of skin or other epithelial lined flaps or grafts
URETHRAL RECONSTRUCTION USING CARBON DIOXIDE LASER
1141
ard fashion to obtain consistent results with the weld. We attribute our success with the laser and solder to the special effects of the protein in the egg albumin which denatures upon application of the laser energy and behaves in a fashion analogous to solder used to join metallic parts with the application of heat. In contrast, when trying to weld the graft to the urethra without solder, too much heat is transferred directly to the graft. Therefore, dessication and destruction of the graft occur resulting in poor healing. Many questions still need to be answered before this technique can be transferred to a clinical setting. Experiments have been designed and are under way: to determine the ideal laser parameters which may be applied to urethral tissue to effect the best weld with the least amount of tissue destruction, to determine the exact function of the protein solder, and the sequence of healing which occurs when laser energy is applied to urethral tissue. Acknowledgments. We are indebted to LaserSonics Division of Cooper Corporation for the use of their CO2 milliwatt laser, to Brian Maddox of Ethicon for supplying microsutures, to Christine Philput, Research and Statistical Consultant at Eastern Virginia Medical School, for the statistical analysis of the data, and to the Microsurgical Research Center of Eastern Virginia Medical School for the use of their facilities. REFERENCES 1. Duckett, J. W.: Hypospadias. In: Campbell's Urology, Fifth Edition,
2. 3. FIG. 4. Intraoperative picture of suture-laser-solder model. Note absence of carbonization along edges where laser weld has occurred.
in the form of a patch or tube to extend the urethral opening to the tip of the penis. 1• 2 In this situation, we found that application of the laser with the protein solder gave superior results that were statistically significant when compared to the use of microsuture alone. Further, this modality of repair reduced operating time by 30%. The use of the laser alone yielded a success rate of only 20%, much lower than with microsuture alone. The egg albumin used in the solder was prepared in a stand-
4.
5. 6.
7.
volume 2. Edited by P. C. Walsh, R. E. Gittes, A. D. Perlmutter and T. A. Stamey. Philadelphia: W.B. Saunders Company, pp. 1969-1999, 1986. Belman, A. B.: Urethra. In: Clinical Pediatric Urology, Second Edition, volume 2. Edited by P. P. Kelalis, L. R. King and A. B. Belman. Philadelphia: W.B. Saunders, pp. 751-792, 1985. Gilbert, D. A., Devine, C. J. and Winslow, B. H.: Microsurgical hypospadias repair. Plast. Reconstr. Surg., 77: 460, 1986. Serure, A., Withers, E., Thomsen, S. and Morris, J.: Comparison of carbon dioxide laser-assisted microvascular anastomosis and conventional microvascular sutured anastomosis. Surg. Forum, 34: 635, 1983. Poppas, D. P., Schlossberg, S. M., Richmond, I. L., Gilbert, D. A. and Devine, C. J.: Laser welding in urethral surgery: improved results with a protein solder. J. Urol., 139: 415, 1988. Ganesan, G. S., Schlossberg, S. M., Poppas, D., Richmond and Devine, C. J., Jr.: Urethral reconstruction using the CO 2 laseran experimental evaluation. Abstract #684, J. Urol. 139: 333A, 1988. Fuller, T. A.: Fundamentals of lasers in surgery and medicine. In: Surgical Application of Lasers. Edited by John A. Dixon. Chicago: Year Book Medical Publishers, pp. 16-33, 1987.