Neourethra creation using autologous vascularized intestinal graft in cats

Abstract

The objective of this study was to assess the application of a urethrostomy technique that utilizes an autologous vascularized intestinal graft as a “neourethra” and to analyze its short- and long-term feasibilities. Six cats with urethral rupture and 8 cats with urethral stricture and a history of urethrostomy were included. The inclusion criteria were the indication for urethroplasty and limited urethral length for perineal urethrostomy. A segment of intestine was prepared as a graft for urethral repair. The diameter of the aboral end was adjusted to facilitate anastomosis with the urethra or neck of the urinary bladder. An ostomy was created in the prepubic region using the oral end. The postoperative follow-up period was at least 1 y. Restoration of urinary flow was successful in all cases immediately after surgery. During postoperative follow-up, minimal complications were observed, with urinary incontinence being one of the most frequent, occurring in 28.5% (4/14) of the cases. Urine culture, carried out at different times during the follow-up period, was positive in 72.7% (8/11) of the cats. The autologous graft from the vascularized intestinal segment was an appropriate urethral substitute and this urethroplasty technique therefore proved to be feasible in cats. The postoperative complications observed were not exclusive to this technique and generally could either be corrected or tolerated. Periodic clinical follow-up examinations are recommended. This procedure allows the reestablishment of urinary flow and should be considered a favorable option, particularly when there is insufficient urethral tissue to allow repair using conventional techniques.

Introduction

Urethral disorders secondary to trauma, stricture, congenital malformation, or neoplasia may require surgical reconstruction using compatible tissues (1). In humans, autologous intestinal segment grafts appear to be useful urethral substitutes with minimal complications (2). Such grafts possess their own blood supply (3) and have a mobile vascular pedicle, tubular shape, flexible walls, and adequate diameter for anastomosis to the urethra and mucosal lining (2).

In veterinary medicine, surgical techniques of urethrostomy for recurrent urethral obstruction have been described (4,5). In cases where the urethral length is insufficient for an ostomy without urethral tension or torsion (6), however, it is necessary to develop and improve grafting techniques and materials that maintain urethral functions with a low rate of complications.

Based on the promising results achieved using the autologous vascularized intestinal segment for urethral replacement in dogs (7), humans (2,8,9), and 1 cat (10), we aimed to apply this urethroplasty technique in cats with limited urethral length that precludes the use of perineal urethrostomy and in which, for some reason, no other conventional urethrostomy technique can be used. We also aimed to analyze the short- and long-term feasibilities of this technique for functional urethral repair.

Due to the preliminary results our research group obtained after applying this technique to a cat (10), we hypothesized that this innovative technique is feasible in this species and is an appropriate option when additional tissue is required for urethral reconstruction and restoration of urinary flow. We also hypothesized that complications such as urethral tension and cicatricial stricture would be minimal with this technique.

Materials and methods

This study was approved by the Ethics Committee on the Use of Animals of the Federal University of Bahia (CEUA-UFBA 19/2018). Owners signed an informed consent form agreeing to their cats’ participation in the study. Fourteen cats with urethral injury in which the location and/or extent of the lesion limited the options for reconstructive urethrostomy techniques were selected.

Anamnesis, physical examination, complementary blood tests (including serum urea and creatinine), and clinical stabilization were carried out on all animals preoperatively. Abdominal ultrasonography was done in cases of suspected urethral rupture, allowing the identification of abdominal free fluid. Due to technical and financial constraints, contrast radiography was unavailable during the study period. Clinical signs and history of previous urethral procedures conducted in other hospitals were also considered for the diagnosis. In some cats, the location and extent of the urethral lesion was only diagnosed during the intraoperative period.

Fifteen minutes before surgery, all animals received cephalothin (Kefalomax; BioChimico, Itatiaia, Brazil), 30 mg/kg body weight (BW), IV and metronidazole (Flagyl; Sanofi-Aventis, São Paulo, Brazil), 15 mg/kg BW. Subcutaneous meloxicam (Maxicam; Ourofino, Cravinhos, Brazil), 0.1 mg/kg BW, was also administered to non-azotemic animals.

Pre-anesthetic medication was administered based on the individual requirements and American Society of Anesthesiologists (ASA) classification of each animal. Intravenous propofol (Propovan; Cristália, São Paulo, Brazil), 4 mg/kg BW, was used to induce anesthesia, which was maintained using isoflurane (Isoforine; Cristália) diluted in 100% medicinal oxygen. All cats received an epidural block with 2% lidocaine hydrochloride without vasoconstrictor (Xylestesin; Cristália), 4 mg/kg BW, and morphine (Dimorf; Cristália), 0.1 mg/kg BW.

Cats were positioned in dorsal recumbency, and their abdominal and pelvic regions were prepared for aseptic surgery. A median celiotomy was carried out. The urethra was identified and carefully isolated, preserving the innervation and vascular supply whenever possible. The urethra was sectioned into the preprostatic segment in 12 cats. In 2 cats in which the original lesion was positioned more cranially, the urethra was sectioned close to the bladder neck.

Autologous vascularized intestinal segment grafts have been prepared for urological reconstruction in dogs and humans (7,8) and we adapted these techniques for cats. An enterectomy approximately 7 cm long was carried out, preserving the mesenteric vascularization (Figure 1 A). The enterectomy site was defined as the first segment of the small intestine, orally/cranially from the cecum, irrigated by vessels from the same branch (usually at ileum or jejunum-ileum transition).

Figure 1.

Photographs of urethroplasty using an autologous vascularized intestinal segment for urethral replacement preparation in cats. A — Identification of the intestinal segment with its vascular supply and mesenteric nerve for subsequent resection for grafting. B — Continuous suture of the mesentery and separation of the autologous vascularized intestinal segment graft. C — Removal of a wedge-shaped wall segment from the aboral end of the graft. D — Intestinal wall synthesis after removal of the wedge-shaped segment. E — Stay sutures passing through the walls of the urethra and graft. F — Immediate postoperative appearance of the ostomy and the Foley catheter fixed to the skin; the superimposed image shows the ostomy area on the 15th postoperative day after removing skin stitches and the Foley catheter.

A simple interrupted suture pattern (4-0 poliglecaprone; Bioline, Anápolis-GO, Brazil) was used for termino-terminal anastomosis of the intestine. The associated mesentery was sutured using 4-0 poliglecaprone in a simple continuous pattern (Figure 1 B). Sodium chloride (0.9%) isotonic solution (Fisiológico; Eurofarma, Ribeirão Preto, Brazil) was injected into the lumen near the anastomosis to check for leakage.

The vascularized intestinal graft was isolated and washed with a warm solution of 0.9% sodium chloride to completely remove the luminal content. To avoid torsion of the graft mesenteric pedicle due to anatomical positioning, the aboral end of the graft was anastomosed to the urethra and the oral end was positioned in the ostomy region.

Subsequently, incisions were made in the abdominal musculature, subcutaneous tissue, and skin of the prepubic region through which the oral end of the graft was passed from the inside to the outside of the abdominal cavity. A Foley catheter (Well Lead Medical, Guangzhou, China) (sizes 6, 8, or 10, depending on the urethral thickness) was passed through the lumens of the graft and remaining urethra (or bladder neck) until the urinary bladder was reached, where the cuff was inflated.

The diameter of the aboral end of the graft was reduced to match the diameter of the urethra. At the aboral end, a 0.5-cm wedge-shaped segment of the wall was removed from the circumference (Figure 1 C) and a simple interrupted 4-0 poliglecaprone suture was applied (Figure 1 D). To carry out the graft-urethra anastomosis, stay sutures were placed around the entire circumference of both walls (Figure 1 E) and the knots were then tightened in a simple interrupted suture pattern. In cats in which the section occurred in the neck of the urinary bladder, anastomosis was conducted directly, without previous reduction in diameter.

Subsequently, the intestinal anastomosis region was omentalized and the abdominal wall was closed in the usual manner using an interrupted cruciate pattern of suture (2-0 Nylon; Bioline) to the musculature, an intradermal suture (2-0 Catgut Chrome; Bioline), and a simple interrupted pattern (3-0 Nylon; Bioline) to the skin.

A 1-cm longitudinal incision was made on the antimesenteric side of the exteriorized graft end to create the ostomy (11). This incision facilitated eversion of the end around its entire circumference, forming a “rosebud”-like shape. It was then sutured to the edges of the skin orifice in the prepubic region using 4-0 poliglecaprone in a simple interrupted pattern, transfixing all layers of the graft wall. Finally, the Foley catheter was attached to the skin using simple interrupted 3-0 surgical nylon sutures (Figure 1 F). A video of the surgical procedure can be accessed at https://www.youtube.com/watch?v=uWdBXywQyKg

After 24 h of hospitalization, the animals were discharged with the following oral prescriptions: amoxicillin with potassium clavulanate (Synulox; Zoetis, Campinas, Brazil), 15 mg/kg BW, q12h for 14 d; metronidazole (Flagyl; Sanofi-Aventis), 15 mg/kg BW q12h for 5 d; tramadol (Dorless; Agener-União, São Paulo, Brazil), 1 to 2 mg/kg BW q8h for 3 d; omeprazole (Gaviz V; Agener-União), 1 mg/kg BW q24h for 14 d; and meloxicam (for non-azotemic cats) (Flamavet; Agener-União), 0.05 mg/kg BW q24h for 2 d.

Other home care recommendations during surgical healing included the use of an Elizabethan collar, disposable diapers over the end of the Foley catheter, and cleaning the surgical wound with a chlorhexidine-based solution. After healing, 14 d following surgery, the Foley catheter and external sutures were removed (Figure 1 F).

Postoperative clinical examinations were carried out at 5, 14, 30, 60, 90, 180, and 360 d to assess the healing process and urination. Follow-up evaluations included anamnesis and conventional physical examination, along with inspection and cleaning of the incision and ostomy, with attention to urine release, the ostium of the ostomy, and surrounding skin conditions.

Serum biochemical tests were done 5 to 30 d after surgery, according to the requirements of each cat and the availability of the cats’ owners. Ultrasonography (Logiq-e; GE Medical Systems, Wuxi, China) of the urinary tract and urine collection through aseptic cystocentesis for urinalysis and culture were carried out at least once between 20 and 360 d after surgery.

Histopathological analysis of the graft was possible on 2 occasions: from a cat euthanized for tracheal obstructive neoplasia 180 d postoperatively (in this case, a tissue sample of healthy ileum from the digestive tract was also obtained as a control) and from a cat that underwent revision surgery for ostomy stricture 1 y after the primary surgery (Figure 2 A to D).

Figure 2.

Histopathological images of the hematoxylin and eosin (H&E)-stained samples obtained from the normal ileum segment in a cat (A) and autologous grafts obtained from the ileum of cats (B, C, and D). A — The ileal fragment that was extracted from the intestinal tract and used as a control sample (H&E, 100×). B — Autologous ileal graft at 6 mo after surgery shows a slight increase in goblet cells (arrows) and submucosal lymphoplasmacytic inflammation (*) (H&E, 200×). C — Autologous ileal graft at 12 mo after surgery shows a marked increase in goblet cells (arrows) and no inflammation (H&E, 100×). D — Histological section of the stenotic ostomy region. A reduction in the size of the lumen (black bars) and bilateral symmetrical fibrosis in the ostomy area (arrows) are seen (H&E, 50×).

Results

Of the 14 selected cats, 8 had urethral strictures (in the ostium of previous urethrostomy or the path of the urethra) and 6 had urethral rupture. All cats were male, without a defined breed, from 3 mo to 14 y old (mean ± SD: 4.2 ± 3.9 y), and weighed 1.2 to 6 kg (mean ± SD: 3.8 ± 1.4 kg).

The location, type, and cause of the urethral lesion, as well as clinical signs, are presented in Table I. In most cases, a combination of clinical signs was observed. The 8 cats with urethral strictures had a history of 1 to 4 previous perineal and/or prepubic urethrostomies (Table I). Urethral ruptures were iatrogenic in 3 cats, due to blunt force trauma/being hit by a car in 2 cats and of unknown cause in 1 cat with signs of urethral obstruction for 3 d.

Table I.

Clinical signs and location, type, and cause of urethral lesions in cats.

Preoperative/ intraoperative information	Description	Number (%)
Location of urethral lesion	Postprostatic pelvic urethra	9 (64.3)
	Preprostatic pelvic urethra	3 (21.4)
	Adjacent to the neck of the urinary bladder	2 (14.3)
Type and cause of urethral lesion	Urethral stricture following previous urethrostomy	8 (57.1)
	Extensive urethral rupture (iatrogenic/unknown cause) and unsuccessful urethral catheterization	4 (28.5)
	Extensive rupture due to blunt force trauma/being hit by a car and unsuccessful urethral catheterization	2 (14.3)
Clinical signs	Unable to urinate on their own	13 (92.9)
	Distended and firm urinary bladder	8 (57.1)
	Free fluid in the abdominal cavity	5 (35.7)
	Scrotal and preputial edema	4 (28.6)
	Unsuccessful urethral catheterization	2 (14.3)
	Vocalization	2 (14.3)
	Stranguria	1 (7.1)
	Penile hemorrhage	1 (7.1)
	Pyuria	1 (7.1)

In 5 cats, the presence of abdominal free fluid, bladder repletion, inability to urinate, and unsuccessful urethral catheterization allowed the diagnosis to be suspected preoperatively. Concomitant traumatic injuries (hematomas in the pelvic region and fracture of the right femur) were observed in 2 cats. In all cases, urethral catheterization was unsuccessful, urethral lesions were extensive, and ruptures were confirmed intraoperatively (Table I). No complications occurred during any surgical or anesthetic procedures.

The proposed postoperative clinical follow-up was sufficient to assess the clinical condition of the cat, healing of the surgical wound, and integrity of the autologous graft, and allowed medical interventions when needed. In 7 cats (7/14; 50%), no complications were identifiable based on anamnesis and physical examination. In the other 7 cats, 1 or more complications occurred (total, 13) at different time periods and with different severities (Table II). Urinary incontinence was the most frequent complication (4/14; 28.5%). Periodic assessments allowed early detection and correction of stricture in the ostomy region in 2 cats (2/14; 14.3%) 1 y after surgery in 1 cat and 6 mo after surgery in the other (Table II).

Table II.

Postoperative clinical signs and information obtained from anamnesis, physical examination, ultrasonography, and urine culture.

Postoperative clinical signs/information	Number (%)
Anamnesis and physical examination
No clinical complications	6/14 (42.9)
Irritation of the skin adjacent to the ostomy	3/14 (21.4)
Frequent licking of the ostomy region	2/14 (14.3)
Graft lumen stricture at the ostomy site	2/14 (14.3)
Marked urinary incontinence	2/14 (14.3)
Skin and subcutaneous incisional dehiscence	1/14 (7.1)
Omental evisceration secondary to body wall dehiscence	1/14 (7.1)
Mild and intermittent urinary incontinence	1/14 (7.1)
Moderate urinary incontinence	1/14 (7.1)
Ultrasound examination
Moderate amount of echogenic sediment suspended in urine	5/14 (35.7)
Small amount of echogenic sediment suspended in urine	4/14 (28.6)
Large amount of echogenic sediment suspended in urine	3/14 (21.4)
Thickening of the urinary bladder wall	3/14 (21.4)
Tiny calculi in the urinary bladder	1/14 (7.1)
Irregularity of the urinary bladder wall	1/14 (7.1)
Urine culture
Not possible to collect urine	3/14 (21.4)
Escherichia coli	3/11 (27.3)
No bacterial growth	3/11 (27.3)
Staphylococcus sp.	2/11 (18.2)
Staphylococcus epidermidis	2/11 (18.2)

Although serum biochemical tests could not always be completed on the desired dates, at least 1 blood sample was obtained from all cats within the first 30 d after surgery. Seven cats were azotemic preoperatively. The mean values of preoperative urea and creatinine levels (130.2 ± 93.1 mg/dL and 3.8 ± 3.7 mg/dL, respectively) decreased considerably (55.4 ± 12 mg/dL and 1.3 ± 0.4 mg/dL, respectively) within 30 d after surgery. Urine culture could be carried out in 11 cats postoperatively [median (interquartile range): 150 (90 to 195) d after surgery]. Gram-negative and Gram-positive bacteria were seen in 3 and 5 samples, respectively (Table II).

Postoperative ultrasonography allowed evaluation of the graft, urinary bladder, adjacent tissues, and other abdominal organs. It was possible to follow the entire path of the graft from the anastomosis to the ostomy. Typical parietal stratification and peristalsis, with different degrees of intensity, were present in all cats. There were no signs of luminal dilation and no or minimal amount of urine in the lumen. The urinary bladder was not distended in any cats. No free fluid or increased echogenicity of the tissues adjacent to the graft that could suggest local inflammation was detected. No relevant alterations were observed in the gastrointestinal tract.

Histopathological analysis of the graft of the euthanized cat (tracheal neoplasia), carried out 6 mo after surgery, revealed a slight increase in goblet cells and submucosal lymphoplasmacytic inflammation (Figure 2 B). In the sample obtained 12 mo after surgery during the revision procedure for ostomy stricture, there was a marked increase in goblet cells and no signs of inflammation (Figure 2 C). These features were not observed in the control sample from the digestive tract (Figure 2 A).

Discussion

To the best of our knowledge, only 1 case report has described the use of urethroplasty with autologous intestinal graft in cats (10). This is the first study to describe and analyze the neourethra technique as a surgical treatment for cats in which urethral length restricted the use of other reconstructive techniques.

The preoperative clinical signs varied according to the cause, location, extent, severity, and duration of injury and were characteristic of compromised urinary flow. All cases presenting with abdominal free fluid were associated with urethral rupture (12). Penile hemorrhage and scrotal and preputial edema were perhaps secondary to the attempted urethral catheterization during previous care at another veterinary center (13).

The Foley catheter is important for adequate healing, reducing the risk of strictures, and preventing urine leakage in the suture line (14). A significant decline in serum urea and creatinine concentrations was expected in the postoperative period after the urinary flow was restored and azotemia was corrected (15).

We observed positive urine cultures in 72.7% (8/11) of the cats; 6 of them exhibited no clinical signs other than minor changes in complementary examinations, such as the presence of urinary sediment (6/6) and thickening (2/6) of the urinary bladder wall on ultrasonography. The other 2 cases with positive urine cultures were discovered in cats with incontinence. Periodic urinalysis by cystocentesis should be carried out for the early detection and treatment of urinary infections (4). The large diameter and different contraction pattern of the intestinal graft compared with a cat’s urethra are factors that may facilitate urinary infections. Urinary infection due to bacteria of the intestinal flora of the graft was considered very unlikely since antibiotics were used prophylactically, in addition to washing the graft lumen.

We believe that the cases of postoperative urinary incontinence were not related to the surgical procedure itself but rather to the location of the lesion (close to the bladder neck) or the involvement of innervation due to the original trauma. Maintaining the maximum possible length of the urethra and innervation of the bladder and urethra are important for maintaining urinary continence (6). Although the surgical procedure was carefully carried out, in both cases in which the anastomosis was done at the bladder neck, there was marked incontinence due to the complete absence of the urethra.

Furthermore, excessive urethral distension in cases of obstruction can compromise innervation and cause incontinence (16). This probably explains the incontinence in the cat that presented with a ruptured urethra after signs of urinary obstruction. The urinary incontinence of the cat that had been run over was possibly related to traumatic injury to the urethral innervation.

The characteristics of an autologous intestinal segment are ideal for grafting as it has no antigenic properties, maintains innervation and vascular supply, and its length is adjustable, which contributes to its healing and integration (2,8). The vascular pedicle showed sufficient mobility to allow anastomosis with the urethra and ostomy site without tension (2). In addition, there were no complications or sequelae in the intestinal region from which the graft was obtained.

The ostomy strictures developed in 2 cats (2/14; 14%) could be correlated with excessive licking of the ostomy site. In both cases, the correction was possible by creating a new ostomy. A study related to conventional prepubic urethrostomy reported a higher rate of stricture of the urethrostomy site (4/16; 25%) at different postoperative periods and the correction was possible in only 1 case, with euthanasia indicated in the others (6). In the present study, the large diameter of the graft compared with the urethra of a normal cat may have contributed to the lower rate of ostomy stricture.

Leakage of urine is a common postoperative complication that is also observed with other urethrostomy techniques (16). Since there were only 4 cats with incontinence in our study, however, and the stricture in the ostomy region occurred precisely in the 2 cats that also showed excessive licking, licking was considered the most likely cause of the stricture and not contact with urine or the surgical technique itself.

Depending on the type and length of the intestinal segment used, long-term complications described in human medicine include metabolic imbalance, malabsorption of vitamins, cholelithiasis, and nephrolithiasis (17). These complications were not observed postoperatively in our patients, probably because graft extracted from the digestive tract was not long enough to cause impairment of the remaining intestinal function.

In our study, histopathological analysis revealed an increase in the number of goblet cells, which has also been observed in ileal grafts in humans (18). The histological changes, observed in both studies, can be considered a tissue adaptation related to the new function of the intestinal graft, which remains in chronic contact with urine. The possibility of adaptation to prevent urine reabsorption was discussed in another study (19).

Long-term follow-up studies and histopathological evaluations can provide more information regarding other changes that may occur over time in the cats included in the present study. The sample size and follow-up time were not sufficient to establish precise correlations between postoperative findings and their causes. Owners of the cats should be aware that lifelong care will be required.

It is important to mention that other surgical techniques, such as transpelvic urethrostomy, would also be feasible for some of the cases included in this study. Due to the cat owner’s limited financial resources and the surgeon’s skill, however, the neourethra technique was the most viable alternative to euthanasia in these cases.

In conclusion, the applied urethroplasty technique proved to be feasible in cats. The ileal graft was a good urethral substitute, allowing the reestablishment of urinary flow. It is a favorable alternative for cases in which there is insufficient urethral tissue to allow repair using conventional techniques. In the present study, the rate of postoperative complications was low and not exclusive to the technique employed. In most cases, complications can be corrected or are well tolerated. Periodic clinical follow-up, including urinalysis and urine culture, are recommended at least every 6 mo.

Funding Statement

The authors thank Coordination for the Improvement of Higher Education Personnel — Brazil (CAPES) for funding the doctoral scholarship (Funding Code 001).