Oral Mucosa Graft: An Ideal Substitute for Urethroplasty

Urethroplasty is both an art and science. The fact that over 200 different types of repair have been reported in the literatures confirms that it is a difficult surgery with many complications and frequently inadequate cosmetic and functional results. (1) There are two main principles of urethroplasty: • Anastomotic technique. • Tissue transfer. The use of vascularized local penile or preputial skin has been the mainstay of urethral reconstruction for a long time. Lacking of penile and preputial skin necessitated the search for new sources for tissue transfer. Resurgence of the use of free grafts for anterior urethral stricture reconstruction has renewed the search for the ideal urethral substitute. (1) Since 1909, a large variety of free extra genital graft tissues had been described in the literature for substitution urethroplasty e.g. ureter (2), tunica vaginalis (3), full thickness extragenital skin (4), and bladder mucosa. (5) For 100 years, oral mucosa had variously been utilized as a free graft in reconstructive plastic surgery. (6) The first report on the application of oral mucosa as a substitute for conjunctiva dated back to 1873 when Stellwag Von Carion used the lip mucosa to treat conjunctival defects. (6) It is generally accepted that Humby, a plastic surgeon, first proposed and reported the use of buccal mucosa in urethral surgery for hypospadias repair in 1941. (7) Whether owing to lack of suitable antibiotic prophylaxis or technical factors, the technique did not gain acceptance or widespread use at that time until almost 50 years later. Current enthusiasm for the technique was promoted by Duckett 1986, (8) Burger and associates 1992 (9), Dessanti and colleagues 1992 (10) and Elkasaby et al. (11) In the following years, numerous reports had described successful use of buccal mucosal graft in the repair of urethral defects associated with previously failed hypospadias surgery and those associated with urethral stricture. (12-19) Nowadays, buccal mucosa has become the mainstay of these tissue transfer techniques. (13) In February 2006, Simonato et al. (20) described the results of the first pilot study on the use of the tongue as an alternative donor site for graft urethroplasty with good functional and aesthetic results. (20) One year later in a dog model, Song et al (21) investigated the feasibility of the LMG urethroplasty. Macroscopic examination of the graft showed no ulceration, calcification, strictures, diverticulae or fistula formation. The junction between


Introduction
Urethroplasty is both an art and science. The fact that over 200 different types of repair have been reported in the literatures confirms that it is a difficult surgery with many complications and frequently inadequate cosmetic and functional results. (1) There are two main principles of urethroplasty: • Anastomotic technique. • Tissue transfer. The use of vascularized local penile or preputial skin has been the mainstay of urethral reconstruction for a long time. Lacking of penile and preputial skin necessitated the search for new sources for tissue transfer. Resurgence of the use of free grafts for anterior urethral stricture reconstruction has renewed the search for the ideal urethral substitute. (1) Since 1909, a large variety of free extra genital graft tissues had been described in the literature for substitution urethroplasty e.g. ureter (2), tunica vaginalis (3), full thickness extragenital skin (4), and bladder mucosa. (5) For 100 years, oral mucosa had variously been utilized as a free graft in reconstructive plastic surgery. (6) The first report on the application of oral mucosa as a substitute for conjunctiva dated back to 1873 when Stellwag Von Carion used the lip mucosa to treat conjunctival defects. (6) It is generally accepted that Humby, a plastic surgeon, first proposed and reported the use of buccal mucosa in urethral surgery for hypospadias repair in 1941. (7) Whether owing to lack of suitable antibiotic prophylaxis or technical factors, the technique did not gain acceptance or widespread use at that time until almost 50 years later. Current enthusiasm for the technique was promoted by Duckett 1986, (8) Burger and associates 1992 (9), Dessanti and colleagues 1992 (10) and Elkasaby et al. (11) In the following years, numerous reports had described successful use of buccal mucosal graft in the repair of urethral defects associated with previously failed hypospadias surgery and those associated with urethral stricture. (12)(13)(14)(15)(16)(17)(18)(19) Nowadays, buccal mucosa has become the mainstay of these tissue transfer techniques. (13) In February 2006, Simonato et al. (20) described the results of the first pilot study on the use of the tongue as an alternative donor site for graft urethroplasty with good functional and aesthetic results. (20) One year later in a dog model, Song et al (21) investigated the feasibility of the LMG urethroplasty. Macroscopic examination of the graft showed no ulceration, calcification, strictures, diverticulae or fistula formation. The junction between 99 vascularized lamina propria ensure quick healing after injury. The immune response is quickly aided by a lamina propria laden with lymphocytes and macrophages. (31) The mucosa covering the lateral and under surface of the tongue is thin, smooth, and identical in structure with the lining of the rest of the oral cavity. Therefore it shares the same advantages such as easy harvesting, favorable immunologic properties (resistance to infection) and tissue characteristics (thick epithelium, high content of elastic fibers, thin lamina propria, rich vascularization) that are favorable properties for imbibition, inosculation, and revascularization of the graft. (27)

Harvesting the oral mucosa
Buccal mucosa may be harvested from the inner surface of the cheek or the inner surface of the upper or lower lip. For a single strip of buccal mucosa to be used as an onlay patch, the adult cheek provides up to 6 cm and the lip 4 cm length with 12 to 15 mm width. It is not advisable to continue the strip of buccal mucosa through the angle of the mouth to combine both cheek and lip segments in continuity for 10 cm. In the experience of Ransley, 1999 (12) the only buccal mucosa donor graft site complicated by a significant contracture was at the angle of the mouth. (12) The mucosa of the cheek is preferable than that of the lip because the mucosa of the cheek is thicker and more robust than the mucosa of the lip. Also, the width of the lip limits the size of the graft. However in terms of outcomes, there is probably little difference between cheek and lip. (12) General anesthesia via endotracheal intubation is the preferred method of airway control to facilitate access to the oral cavity. A surgical marking pen is used to outline the extent and shape of the graft away from the parotid papilla. The area should not encroach on the mental nerve, nor extend further back than the pterygomandibular raphe, and leave a cuff of mucosa 1 cm from the labial commissure. (14) The graft is better outlined as an elliptical shape, which eases closure of the anterior and posterior aspects of the donor site without compromising graft size or viability. A graft that is at least 10% longer and 10 -20% wider than actually necessary is obtained to allow for shrinkage. (33) Hydro-dissection of the oral mucosa from the underlying soft tissues using 1% lidocaine with 1:100,000 epinephrine and the the use of a No. 15 blade is recommended so that the incision is limited to the full thickness of the mucosa only. (34) Dissection of the buccinator muscle can lead to damage of the buccal neurovascular bundle. Also, branches of the facial nerve lying deep within this muscle would not be damaged by this incision. (9) Harvesting the graft is slightly painful but not disabling in the post-operative period. Pain appears to be worse in the immediate post-operative period after suturing the harvest site. There is no difference in long-term post-operative morbidity whether the graft site is closed or left open however, some authors recommended to leave the buccal mucosa harvest sites unsutured. (35) Post-operative discomfort can be lessened by a diet of soft meals and by cleansing of the wound daily with povidone iodine solution. Some difficulty with mouth opening might be experienced during the early postoperative period but it will return to the normal range even if complications of wound healing have occurred. (9) Harvesting lingual mucosal grafts follows the basic principles as that of the buccal mucosa with few differences. Harvesting the tongue should be technically easier than from the inner cheek since the tongue can be pulled out of the mouth with a traction suture. (Fig. 1) www.intechopen.com

Tips and tricks in the urethroplasty
Oral mucosa may be used as an onlay patch if the urethral plate is retained, as a complete tube if there is no available urethral plate or in various ways combined with other tissues. (30) However, two main problems are faced using buccal mucosa as a tube graft. First, strips of oral mucosa should not be tubularized lengthwise to create 6 cm or 4cm tubes, because the width is insufficient. They can be folded lengthwise to provide shorter tubes of up to 3cm and 2cm, respectively or a second graft of similar dimensions can be applied to create a fulllength cylinder of adequate diameter. (12) Another problem with tube grafts in general is the inadequate graft take, as they are not circumferentially surrounded by vascularized tissue leading to increased incidence of contraction and anastomotic stricture that have led some to avoid tube grafts in favor of onlay procedure. (13,37) Traditionally, grafts have been placed on the ventral aspect of the urethra because it allows for easier access to the urethra and better visualization of the stricture. However, with a higher reported incidence of diverticula formation, due to poor support, and consequently postvoid dribbling and ejaculatory dysfunction. (38) Barbagli et al (39) introduced the dorsally placed graft and postulated that dorsal placement is advantageous as it allows better mechanical support for the graft with a richer vascular bed from the underlying corporeal bodies. (39) However, they recently compared the results of buccal mucosal urethroplasty in 50 patients with bulbar urethral strictures. Buccal mucosa grafts were placed on the ventral, dorsal and lateral bulbar urethral surface in 17, 27 and 6 cases, respectively. They reported that the placement of buccal mucosa grafts into the ventral, dorsal or lateral surface of the bulbar urethra showed the same success rates (83% to 85%) and the outcome was not affected by the surgical technique. Moreover, stricture recurrence was uniformly distributed in all patients. (40)

The process of take
The free graft initially adheres to its new bed by fibrin, and revascularization is achieved by the outgrowth of capillary buds from the recipient area to unite with those on the deep surface of the graft. This link up is usually well advanced by the third day. During this period (first 48 h.), the graft depends on imbibitions from the surrounding tissue. At the same time with the vascular link-up, the fibrin is infiltrated by fibroblasts, which gradually convert the initial weak adhesion provided by the fibrin clot into a definitive attachment by fibrous tissue. The strength of this attachment increases quickly, providing an anchorage within 4 days, which allows the graft to be handled safely if reasonable care is taken. More slowly a lymphatic link up is added and, even more slowly, nerve supply is re-established, although imperfectly and invariably. Of these various processes the ones most relevant in clinical practice are vascularization and fibrous tissue fixation. The speed with which this is accomplished, is determined by the characters of the bed on which the graft is laid, the characteristics of the graft itself, and the condition under which the graft is applied. (41) The bed on which the graft is laid must have fibrinogen and the enzymes, which convert it into fibrin in sufficient quantities to provide the necessary adhesion. Sometimes the surface is harboring streptococcus pyogens, which destroys fibrin by its potent fibrinolysin action. Also, the bed should have enough blood supply to vascularize the graft. Rapid vascularization is important, and the distance to be traveled by the capillary buds in order to link-up clearly needs to be as short as possible. The graft has therefore to be in the closet possible contact with the bed. The most frequent cause of separation is bleeding from the bed; the resulting haematoma acts as a block to link-up of the outgrowing capillaries. (42) The graft has also to lie immobile on the bed until it is firmly attached. In particular, shearing strains, which tend to make the graft slide to and fro and prevent capillary link-up, are to be avoided until the initial fibrin adhesion has been converted into a strong fibrous tissue anchorage. (42) In summary, the graft take requires a bed that is capable of providing the necessary capillary outgrowth to vascularize a graft, free of pathogens inimical to graft take in addition to an immobile close contact between graft and bed. The most frequent cause of graft loss is the presence of a hematoma which separates the graft from its bed and or shearing movements which prevent adhesion between graft and bed, each in its own way preventing capillary link up and vascularization. (42)

Indications
In patients with congenital or acquired urethral defects, short or lengthy segments of the urethra need to be reconstructed. Vascularized preputial and penile shaft skin flaps are frequently used to achieve this. (43) After repeated previous surgery there is lacking of penile and preputial skin and the blood supply of these skin flaps is disturbed so that free graft material is preferred. Free skin graft material from extragenital regions is less suitable due to the thickness, hair growth or tendency to contract. The use of bladder mucosal free graft includes the additional and not inconsiderable burden for the patient arising from graft harvesting, and is procedurally quite complicated. Furthermore, postoperative complications caused by cauliflower-like deformities in the meatus externus urethrae are frequent. These aspects have greatly reduced the potential of this operating technique. (5) The first very good results of buccal mucosa as a free graft encourage its usage in these situations. El-Kassaby and associates, 1993 (11) recommended the use of buccal mucosal graft in the treatment of anterior urethral stricture. They used this technique for treatment of short strictures (1 to 2cm) that usually required a 2 to 4 cm repair, making excision and endto-end anastomosis impractical. Buccal mucosa has also been used to replace urethra in epispadias repairs in exstrophy patients whose penile skin is insufficient. (

Advantages
• Easily accessible, non-hair bearing and the supply source is constant and adequate.

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The intraoral donor site guarantees an excellent cosmetic result.

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The graft is extremely elastic and shows only a slight tendency to contraction.

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The graft has been noted to retain the elasticity of the virgin tissue.

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The meatal problems of excoriation, encrustation and protuberance that encountered with bladder mucosa, have not been a problem with buccal mucosa.

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High resistance to infection and trauma and high regenerative power. • Buccal mucosa is characterized by thick epithelial layer and thin lamina propria that make the graft mechanically stiff and easy handled and aid in rapid vascularization of the graft.

Disadvantages
• The oral mucosa cannot be tubularized to create long tubes because the width is insufficient. So, it can be folded lengthwise to provide shorter tubes or a second flap of similar dimensions can be applied to create a full-length cylinder of adequate diameter.

•
It may lead to a significant contracture at the angle of the mouth if the buccal mucosal graft is taken through the angle.

•
Liability of injury to superficial branches of the facial nerve. • Stricture and fistula continue to be a problem with buccal mucosa as with any other free graft.

Results of oral mucosa urethroplasty
There is no doubt, both subjectively and objectively, that oral mucosa is proving very satisfactory as a material for urethral reconstruction. This may be due to growth factors within the mucosa that promote rapid healing, revascularization occurs quickly because of the thin lamina propria and the originally highly vascular bed from which the buccal mucosal graft was taken. (43) In their early report of the use of buccal mucosa in hypospadias repair, Dessanti and associates, 1992 (10) reported only one case of urethral fistula out of 8 hypospadias patients after 6-18 months of follow up. Another two patients required urethral dilatation during the initial 4 weeks because of mild anastomotic stenosis. No meatal problems such as stenosis or granulomatous reactions was observed. (10) Similarly, Burger and associates (9) in the same year used buccal mucosa in 6 patients; failed hypospadias repair (3), severe stricture after hypospadias repair (1), short urethra (1) and epispadias in 1 patient. The results were 3 urethral fistulae and 1 meatal stenosis in 3 patients. No urethral stricture or diverticulum was noted, and the final outcome was good functionally and cosmetically in all patients. (9) One year later El-Kasaby and associates (11) reported their experience with buccal mucosa patch graft in the management of 20 patients with anterior urethral strictures. Results were excellent in 18 patients while 2 required revision for recurrent stricture. (11) The experience of Ransley and Manzoni, 1999 (12) with buccal mucosal graft extended to more than a 100 case. They reported a secondary operation rate of approximately 20%, which are mostly due to minor fistulae or the need for meatal revision. Radical reoperation with further urethral augmentation with an additional buccal mucosal graft had been necessary on some occasions. They recommended the use of preoperative testosterone treatment in difficult cases to improve the vascularity of the penile skin and thereby enhance the chances of success with a free graft technique. (12) Barbagli and associates (39)  At that time, we concluded that urethral reconstruction using buccal mucosa is a useful technique and the results appear to be acceptable given the difficulty of the cases in which buccal mucosa was used. The structure, function and ease of working with buccal mucosa make it the ideal extragenital source for reconstruction of the urethra in complex hypospadias and urethral stricture. Easiness of harvesting and rapid healing process also contributes to its superiority. As in all urethral reconstructions, the learning curve is long. However, as one becomes more familiar with urethral reconstruction using buccal mucosa, no doubt the complication rate will decrease measurably. (46) Among the good results of the oral mucosa urethroplasty, the lingual mucosa is no exception. In their pioneering report, Simonato et al (20) reported seven successful cases out of the 8 cases included in his study achieving a success rate of 87.5%. (20) In a following report, they reported a series of 29 patients with anterior urethral strictures who underwent urethral reconstruction using LMG. The mean stricture length was 3.6 cm (range, 1.5-9.0 cm). The length of the LMG used ranged from 3 cm to 9 cm (mean, 5.3 cm), with a mean width of 1.5 cm. Mean follow-up time was 17.7 months (range, 6-71 months). The overall early stricture recurrence was 20.7%. (27) Since then a number of groups have investigated the feasibility of lingual mucosa graft urethroplasty (16, 17, 21-23, 25, 26, 29, 30, 36, 47) whether experimentally (17,21) or clinically, (16,22,23,25,26,29,30,36,47) alone or with buccal mucosa, (16,17) and with different urethroplasty techniques. (23,26,47) Barbagli et al (25) later described their early experience using LMG for urethral reconstruction in 10 patients with anterior urethral strictures. The length of urethral strictures was 2-6 cm and the length of the lingual grafts was 4-6 cm (mean, 4.5 cm) with a width of 2.5 cm. Mean follow-up time was 5 months (range, 3-12 months); nine cases (90%) were successful. (25) We have also described our early results of lingual mucosa urethroplasty in 18 patients with long recurrent strictures of the anterior urethra. (29) Their mean age was 39.5 years (18-66 years), and the mean stricture length was 4.36 cm (3-9 cm). Of the 18 cases, 6 were penile, 8 bulbar, and 4 bulbopenile. The primary etiology was traumatic in 8 cases, iatrogenic in 6 cases, and inflammatory in 4 cases. Previous stricture treatments included dilations in all 18 patients, optical internal urethrotomy in 14, hypospadias repair in 2, and failed BMG urethroplasty in 2. The graft was placed dorsally in 12 cases and ventrally in 6 cases. The mean operative time was about 177 mins (140-210 mins) using a one-team approach. The length of the LMG used ranged from 4-10 cm and a width of 1.5 cm. The graft was harvested unilaterally in 15 (83%) cases and bilaterally in 3 (17%) cases. There was no need for intraoperative blood transfusions, and there were no major perioperative complications. (29) There were 15 successful cases (83.3%), 2 patients had restricture at the anastomotic site, and 1 patient showed a urethrocutaneous fistula. In the successful cases, there were no residual strictures and no urethral diverticulae or sacculations in their urethrograms at 3 months. The peak flow rate improved from a mean of 4.98 ml/s (0.6-8.6 ml/s) to 27.28 ml/s (22.4-39.6 ml/s). Urethroscopy was done in 10 out of the 15 successful cases and revealed that LMGs were almost indistinguishable from the native urethra. (29) In another prospective randomized controlled study, we compared outcomes as well as donor site complications of buccal mucosal graft (BMG) (20 patients) versus lingual mucosal graft (LMG) (20 patients) dorsal onlay urethroplasty in 40 patients with anterior urethral strictures. Early and late complications, success rate and patient satisfaction were compared between the two groups. The number of patients with pendulous, bulbar and bulbopendulous strictures as well as the mean stricture length and mean follow-up were comparable between the two groups. No significant difference between both groups in the operative time, hospital stay, early postoperative pain and time to resume fluid intake and normal diet. Late after surgery, the postoperative pain, perioral numbness and tightness of the mouth as well as changes in salivary function were significantly higher in the buccal mucosa (BMG) group versus the lingual mucosa (LMG) group (p < 0.01). The success rate in both groups was similar (90% in the BMG group and 85% in the LMG group) (p > 0.05). In the BMG group 80% and in the LMG group 85% said they would recommend this procedure to another patient (p > 0.05).

Conclusion
Being easy to harvest and to handle, immune to infections and accustomed to a wet enviroment, the oral mucosa displays many inherent characteristics of an ideal graft substitute for urethroplasty.