Case report laparoscopy-assisted pre-pubic urethrostomy as a palliative procedure for resection of distal urethral tumor in a female dog.

BACKGROUND: This paper presents the first described case of laparoscopy-assisted prepubic urethrostomy and laparoscopic resection of a tumor of the distal part of the urethra in a female dog as a palliative treatment. CASE PRESENTATION: An intact, 11 -year-old, mixed breed female dog, weighing 15 kg, was admitted with signs of urinary obstruction and difficulty with catheterization. Vaginal, rectal, and endoscopic examinations revealed a firm mass in the pelvic cavity at the level of the pelvic urethra. Ultrasound and computed tomography examination showed enlargement of the urethral wall (5.5 cm width and 3 cm thick), which was significantly restricting the patency of the urethra. The lesion affected only the distal part of the urethra without the presence of local or distant metastatic changes. The affected portion of the urethra was laparoscopically removed while performing pre-pubic urethrostomy with laparoscopy. The patient regained full consciousness immediately after the end of anesthesia, without signs of urinary incontinence. Histopathological examination of the removed urethra revealed an oncological margin only from the side of the bladder. In the period of 2.5 months after the procedure, the owner did not notice any symptoms that could indicate a postoperative recurrence, which was diagnosed three months after the procedure. CONCLUSIONS: Pre-pubic urethrostomy can be successfully performed with the assistance of laparoscopy. The use of minimally invasive surgery will allow, in selected cases, removal of the urethral tumor, and in inoperable cases, to perform a minimally invasive palliative pre-pubic urethrostomy.

RADIATION THERAPY OF A PRESUMPTIVE URETHRAL TRANSITIONAL CELL CARCINOMA IN AN EASTERN GRAY SQUIRREL (SCIURUS CAROLINENSIS).

An adult female Eastern gray squirrel (Sciurus carolinensis), with a previous history of primary renal transitional cell carcinoma treated by nephrectomy, was diagnosed with a metastatic urethral transitional cell carcinoma (TCC) utilizing the veterinary bladder tumor antigen test in combination with other noninvasive diagnostic tests. The squirrel was treated with piroxicam and external beam radiation therapy given in 18 treatments over 30 days to achieve a total of 54 gray. Mild to moderate side effects from the pelvic irradiation were self-limiting and easily managed. Resolution of clinical signs was achieved for approximately 6 mo until recurrence of metastasis. This report represents the first published account of both TCC and external beam radiation therapy in an Eastern gray squirrel.

Total cystectomy for treatment of transitional cell carcinoma of the urethra and bladder trigone in a dog.

OBJECTIVE: To report total cystectomy with reimplantation of the ureters in the proximal aspect of the vagina. STUDY DESIGN: Case report. ANIMALS: An 11-year-old female spayed Vizsla with spontaneously occurring transitional cell carcinoma of the urethra and bladder. METHODS: After initial treatment for transitional cell carcinoma of the bladder trigone with urethral stent placement and chemotherapy, the dog developed urinary incontinence 2 months after stent placement. Eleven months after initial diagnosis, the dog developed pulmonary metastasis and local progression, leading to bilateral ureteral dilatation. After palliative radiation, total cystectomy was performed. RESULTS: The owners elected euthanasia 442 days after original presentation and 92 days after total cystectomy. Euthanasia was unrelated to the surgical procedure, but was related to the primary disease. CONCLUSIONS: Total cystectomy is a technically feasible procedure that should be considered for the treatment of bladder cancer in dogs.

Novel surgical approach to neoplastic lesions in the distal part of the urethra: A pilot cadaver study comparing open and hybrid techniques.

Tumours of the distal urethra in female dogs are often difficult to treat, and the surgical methods described thus far have technical limitations. This study aimed to present a novel approach to the surgical treatment of distal urethral tumours. This study used dog cadavers to evaluate the technical feasibility of surgically removing neoplastic lesions in the distal urethra and compared surgical outcomes of open surgery with those of hybrid surgery (combination of laparoscopy and open surgery). Open intact, open spayed, hybrid intact, and hybrid spayed dog cadaver groups underwent surgery (n = 6 per group). The novel surgical method was based on vulvovaginectomy (ovariohysterectomy in intact dogs), resection of the distal part of the urethra, and pre-pubic urethrostomy. Outcomes of interest included technical feasibility of each procedure, using both surgical techniques, wound length, time required to complete the procedure, and the incidence of intraoperative ureter and rectum injuries. Surgical technique and reproductive status affected operating time. Technique choice affected wound length; the surgical wound was longer in the open group than in the hybrid group. Macroscopic evaluation of the rectum did not reveal any damage to the wall. There was no evidence of ureter leakage or obstruction in any case. The present findings suggest that both open and hybrid surgery can be used to treat distal urethral tumours.

Metastatic transitional cell carcinoma in proximal humerus of a dog.

Transitional cell carcinoma (TCC) was diagnosed in the proximal humerus of a dog that was presented with persistent right forelimb lameness with no clinical signs of urinary tract involvement. A diagnosis of TCC was made from surgical biopsy of the humeral lesion with subsequent necropsy revealing the prostatic urethra as the primary site of the tumor.

Longitudinal assessment of B-RAF V595E levels in the peripheral cell-free tumor DNA of a 10-year-old spayed female Korean Jindo dog with unresectable metastatic urethral transitional cell carcinoma for monitoring the treatment response to a RAF inhibitor (sorafenib).

Transitional cell carcinoma (TCC) is the most common malignant tumor of the canine urinary tract. In this case study, a dog with metastatic urethral TCC was treated with sorafenib. The tumor expression levels of receptor tyrosine kinase genes, including VEGFR-1, VEGFR-2, PDGFR-α, PDGFR-ß, ALK, EGFR, ErbB2, and B-RAF, were analyzed. VEGFR was overexpressed in tumor tissues compared to the normal tissues. Considering the high frequency of B-RAF mutation in canine urological tumors, the B-RAF gene was examined, and the B-RAF V595E mutation was detected in the tumor tissue. Therefore, the antitumor effect of sorafenib, a multi-tyrosine kinase inhibitor, on unresectable metastatic urethral TCC characterized by B-RAF V595E was evaluated and circulating cell-free tumor DNA (ctDNA) was assessed for monitoring the treatment response. After the initiation of oral sorafenib therapy (4 mg/kg/day escalated to 10 mg/kg/day), the dysuria was alleviated gradually, and the patient remained stable for 3 months. During that treatment period, the patient showed various levels of changes associated with B-RAF V595E mutation in ctDNA as evident from longitudinal plasma samples after initiation of sorafenib therapy. The findings of this study suggest that ctDNA may serve as a useful non-invasive tool for monitoring the treatment response to anticancer drugs.

Evaluation of microsatellite instability in urine for the diagnosis of transitional cell carcinoma of the lower urinary tract in dogs.

BACKGROUND: The accumulation of frame-shift mutations in microsatellites (MS), termed microsatellite instability (MSI), is associated with certain tumors. MSI and its detection in urine samples has been used to aid in the detection of human bladder cancer. HYPOTHESIS: Evaluation of MSI in urine is a useful assay test for diagnosis of transitional cell carcinoma (TCC) in dogs and is more specific than the commercially available, veterinary bladder tumor analyte (V-BTA) test. ANIMALS: Seventy-three dogs: healthy controls (n=21), proteinuric (n=12), lower urinary tract disease excluding TCC (n=17), and TCC (n=23). METHODS: Prospective observational study. Urine samples collected from each animal were evaluated for MSI and using the V-BTA. For MSI detection, 22 MS sequences were polymerase chain reaction amplified from urine and blood, subjected to capillary electrophoresis, and the MS genotypes were compared. Aberration in ≥15% of MS was considered indicative of MSI. RESULTS: MSI was detected in 11 of 23 (48%) urine samples from dogs with TCC. MSI was also detected in 12 of 50 (24%) of the control animals, including 29, 16, and 24% of healthy, proteinuric, and lower urinary disease dogs, respectively. In this population, sensitivity and specificity of MSI analysis was 48 and 76%, respectively, compared with 83 and 64%, respectively, for the V-BTA test. CONCLUSIONS: MS analysis as performed in this study is not useful in the diagnosis of TCC.

Novel Noninvasive Diagnostics.

Molecular diagnostics have revolutionized human oncology to allow early detection, targeted therapy, monitoring throughout treatment, and evidence of recurrence. By identifying genetic signatures associated with cancers, liquid biopsy techniques have been developed to diagnose and monitor cancer in noninvasive or minimally invasive ways. These techniques offer new opportunities for improving cancer screening, diagnosis, and monitoring the impact of therapy on the patients over time. Liquid biopsy also drives drug development programs. Similar diagnostics hold promise for comparable results in the veterinary field. Several noninvasive/minimally invasive techniques have been described in veterinary medicine that could be referred to as liquid biopsy.

Incomplete Urethral Duplication Associated with a Dermoid Cyst in a Dog with Urinary Obstruction.

A 20-month-old male miniature dachshund was evaluated for a 10-week history of intermittent stranguria, pollakiuria, haematuria and obstructive urolithiasis. Retrograde urethrocystography revealed a subcutaneous saccular structure in the perineal area connected to the intrapelvic urethra associated with urolithiasis. After excision of the perineal saccular structure, microscopical examination confirmed the presence of transitional epithelium lining the diverticulum, with isolated submucosal smooth muscle bundles. This structure was attached to another saccular structure lined by stratified squamous keratinizing epithelium with hair follicles, sebaceous glands and apocrine glands. An incomplete urethral duplication with dermoid cyst was diagnosed. The dog recovered uneventfully from surgery and was still urinary continent and free from clinical signs 5 months after surgery. To the authors' knowledge this is the first report of an incomplete urethral duplication with a dermoid cyst and concurrent obstructive urolithiasis in a dog.

Evaluation of palliative stenting for management of malignant urethral obstructions in dogs.

OBJECTIVE: To evaluate use of balloon-expandable and self-expanding metallic stents in management of malignant urethral obstructions in dogs. DESIGN: Original study. ANIMALS: 12 dogs with malignant urethral obstructions. PROCEDURES: The extent and location of urethral obstructions and the diameter of adjacent unaffected luminal segments were determined by use of fluoroscopically guided wires and measuring catheters. Stents were chosen to extend approximately 1 cm proximal and distal to the obstruction. Stent diameters were chosen to be approximately 10% greater than the diameter of healthy portions of the urethra to prevent displacement. Stents were placed in the urethra under fluoroscopic guidance to restore luminal patency. RESULTS: 3 dogs received balloon-expandable metallic stents, and 9 dogs received self-expanding metallic stents. The placement procedures were rapid, safe, and effective at restoring luminal patency and were not associated with major complications. Complications included recurrent urethral obstruction secondary to blood clot formation and urethral edema in 1 dog and stent dislodgement into the urinary bladder in 1 dog. All dogs were able to urinate immediately after the procedure. Nine dogs (3/4 females and 6/8 males) were continent or mildly incontinent after stent placement. Of the remaining 3 dogs, 2 developed severe incontinence and 1 had an atonic bladder. Seven dogs were considered to have good to excellent outcome, 3 had fair outcome, and 2 had poor outcome. CONCLUSIONS AND CLINICAL RELEVANCE: Transurethral placement of metallic stents was a safe and effective palliative treatment option for dogs with malignant urethral obstructions.

Evaluation of carbon dioxide laser ablation combined with mitoxantrone and piroxicam treatment in dogs with transitional cell carcinoma.

CASE DESCRIPTION: 8 dogs that underwent carbon dioxide (CO2) laser ablation of transitional cell carcinoma in the bladder trigone and proximal portion of the urethra and were also treated with mitotranxone and piroxicam. CLINICAL FINDINGS: Transitional cell carcinoma of the bladder frequently involves the trigone and urethra and can be difficult to manage surgically. Dogs underwent laser ablation of the primary tumor and were treated with mitoxantrone at a dosage of 5 mg/m2)every 3 weeks for 4 treatments. Piroxicam was given at a dosage of 0.3 mg/kg (0.14 mg/lb) once daily for the remaining life of the dog. TREATMENT AND OUTCOME: Median and mean disease-free intervals were 200 and 280 days, respectively. Median and mean survival times were 299 and 411 days, respectively. Adverse treatment effects were observed in 2 dogs; signs included mild, self-limiting inappetance and lethargy. The procedure appeared to be well tolerated; all treated dogs had rapid resolution of clinical signs of disease of the lower portion of the urinary tract. CLINICAL RELEVANCE: Although survival times achieved with CO2 laser ablation and treatment with mitoxantrone and piroxicam were similar to survival times associated with chemotherapy alone, resolution of clinical signs was better with the combined treatment.

Urethral transitional cell carcinoma in a cat.

A 15-year-old, male neutered cat was referred for investigation of dysuria. A retrograde urethrography was performed which showed two space-occupying masses within the lumen of the mid-to-proximal urethra. Exploratory coeliotomy revealed two urethral masses. Segmental urethrectomy was performed to resect the mass, and the lower urinary tract was reconstructed by vesico-urethral anastomosis. Histopathology showed the mass to be a transitional cell carcinoma with incomplete surgical margins. Tumour regrowth was suspected when dysuria was found approximately 318 days after surgery. Clinical signs were palliated by radiation using weekly fractions of 6 Gy for three weeks. The cat died of unknown causes 386 days postoperatively.

Bacterial urinary tract infections associated with transitional cell carcinoma in dogs.

BACKGROUND: Urinary tract infections (UTI) are believed to be common in dogs with transitional cell carcinoma (TCC), but incidence and contributing factors have not been reported. OBJECTIVES: To determine the frequency and bacterial agents associated with UTI in dogs with TCC and define contributing factors. ANIMALS: Eighty-five dogs with a history of urogenital TCC undergoing treatment with chemotherapy that had at least 1 urine culture performed. METHODS: Medical records and culture results were retrospectively reviewed and ultrasound images were reviewed when available. Clinical factors were evaluated statistically for association with positive culture. RESULTS: Fifty-five percent (47/85) of dogs had at least 1 positive culture during the course of treatment. Female dogs (80%, 40/50) were more likely than male dogs (29%, 10/35) to have at least 1 positive culture. Ultrasound examination determined that female dogs were more likely to have urethral (74%, 31/42) or trigonal tumor involvement (71%, 30/42) compared to male dogs (32%, 9/28 and 43%, 12/28, respectively). The most commonly isolated organisms were Staphylococcus spp. (23.9%, 29/121) and Escherichia coli (19.8%, 24/121). Dogs with urethral involvement of TCC were significantly more likely to have at least 1 positive culture than dogs without urethral involvement (75%, 30/40 versus 30%, 9/30). CONCLUSIONS: Urinary tract infection is common in dogs with TCC highlighting the importance of regular monitoring for bacterial cystitis in dogs with TCC. In addition, clinical factors such as tumor location and sex may be predictive of positive culture and can help clinicians assess the risk of UTI.

Pathology of canine bladder and urethral cancer and correlation with tumour progression and survival.

Biopsy and necropsy specimens, comprising 107 primary carcinomas and three mesenchymal tumours, were reviewed from 110 dogs with cancer of the bladder, urethra, or both. Histological classifications developed for the assessment of human bladder cancer were found to be readily applicable to the dog. These classifications are based on histological features, including the pattern of growth, the cell type, the grade of transitional tumour and the depth of invasion of the bladder wall. Features associated with localized disease in canine transitional cell carcinoma included papillary architecture, "in-situ" tumour, low tumour grade and a strong peritumoral lymphoid cell reaction. Features of tumours with metastasis included infiltrating and non-papillary architecture, increasing tumour grade, depth of invasion, vascular invasion and presence of peritumoral fibrosing reaction. Wide variability was found within single tissue samples, indicating that multiple sample sites are necessary for the adequate characterization of a given lesion. Statistically significant correlations were found between: tumour grade and depth of invasion (P < 0.0001); tumour grade and presence of metastases (P < 0.029); and peritumoral desmoplasia and metastases (P < 0.029). It was concluded that canine bladder cancer could be classified for the purpose of clinical management with a modified World Health Organization system as developed for human tumours.

Squamous cell carcinoma of the equine external genitalia: a review and assessment of penile amputation and urethrostomy as a surgical treatment.

A retrospective analysis was performed on 48 cases of suspected neoplasia involving the equine external genitalia. Forty nine squamous cell carcinomata (SCC) and 23 squamous papillomata (SP) were identified. Two cases of epithelial hyperplasia and one case of habronemiasis were also recognised histopathologically. The glans penis was the most common site of tumour development accounting for 53 per cent of cases of SCC and 61 per cent of SP. The urethral diverticulum, urethral process or urethra was involved in 27.6 per cent (8/29) of cases of SCC. Twelve per cent (5/41) of cases of SCC were confirmed to have metastatic involvement of the local lymph nodes. Papillomata showing pre-malignant changes were identified in five cases. Seventy five per cent (36/48) of the animals presented were ponies. All were geldings, mean age 16.5 years. Penile amputation and urethrostomy, preputial ablation and proximal urethrostomy or local excision were used in the surgical management of these animals; three cases were inoperable and destroyed at presentation. Oedema, haemorrhage and stenosis of the urethrostomy site were encountered as post operative complications. Sixty six per cent (6/9) of animals with SCC of the glans penis (without urethral involvement), which had a known history over the follow up period, treated by penile amputation and urethrostomy survived for longer than 18 months. Similarly, of those with urethral involvement only 28.6 per cent (2/7) survived for a similar follow-up period. SCC not uncommonly affects the external genitalia of aged pony geldings and frequently the glans penis. If the lesion is identified before local metastasis occurs, penile amputation and urethrostomy is indicated and the prognosis is favourable.

Canine bladder and urethral tumors: a retrospective study of 115 cases (1980-1985).

One hundred and fifteen dogs with neoplasms of the lower urinary tract (bladder and/or urethra) were retrospectively evaluated at five referral institutions participating in ongoing studies by the Veterinary Cooperative Oncology Group. Most tumors were malignant (97%) and of epithelial origin (97%). Lower urinary tract tumors were more common in older dogs weighing greater than 10 kg. The following significant (P less than 0.05) statistical associations were found using the University of Guelph hospital population as control; there was no sex predisposition although the female:male ratio was 1.95:1. Neutered dogs were predisposed as were Airedale Terriers, Beagles, and Scottish Terriers, whereas German Shepherds were significantly under-represented among dogs with lower urinary tract tumors. These statistical associations should be interpreted cautiously because of possible demographic differences in hospital populations among the University of Guelph and other cooperating institutions. There were no significant correlations between age, gender, weight, breed, response to therapy, and survival time. Clinical signs were indicative of lower urinary tract disease and included hematuria, stranguria, and pollakiuria. The laboratory data were nonspecific except for urinalysis test results. Hematuria and inflammatory urinary sediments were most commonly reported; neoplastic cells were identified in the urine sediment of 30% of dogs with lower urinary tract tumors. Contrast cystography was a useful noninvasive diagnostic method since 96% of the dogs had a mass or filling defect in the lower urinary tract demonstrated by this technique.(ABSTRACT TRUNCATED AT 250 WORDS)

Cisplatin (cisdiamminedichloroplatinum) for treatment of transitional cell carcinoma of the urinary bladder or urethra. A retrospective study of 15 dogs.

The records of 15 sequential cases of transitional cell carcinoma of the urinary bladder or urethra in dogs were examined to determine the results of treatment with cisplatin (cisdiamminedichloroplatinum) and to record and assess toxicities. All dogs had measurable disease and were considered eligible for evaluation of toxicity following one cisplatin treatment. Three dogs were eliminated from evaluation of efficacy because of acute toxicities. Of the 12 remaining dogs that received two or more cisplatin treatments, evaluations at the end of the second month of treatment revealed no complete responses; however, three dogs showed partial responses and six dogs maintained stable disease. Three dogs had tumor progression. The median survival time for these 12 dogs was 180 days (mean, 220 days; range, 36 to 589 days). Three dogs were azotemic before treatment. Two of these dogs showed improvement in renal function following therapy. Six of the other twelve dogs developed increases in serum creatinine during therapy. The objective and subjective improvements of some dogs to cisplatin chemotherapy suggest that this agent is active in selected dogs with transitional cell carcinomas of the urinary tract.

Urethral leiomyoma in a cat.

A 13-year-old spayed cat was examined because of a suspected lower urinary tract obstruction. After 2 days, a urethral catheter could not be passed, and the cat was euthanatized. At necropsy, a 1.2-cm intramural mass was detected, obstructing the proximal portion of the urethra. Histologic examination of the well-circumscribed mass revealed a urethral leiomyoma.

Simultaneous cystometry and uroflowmetry for evaluation of micturition in two dogs.

A recently developed urodynamic testing procedure was used to evaluate disorders of micturition in 2 dogs. The procedure simultaneously recorded intravesical pressure and urine flow during micturition. In an 11-year-old spayed female Sheltie that could not urinate normally, a micturition study demonstrated functional outflow obstruction of the urinary bladder. Although the urethra was patent, the urethral resistance factor, as calculated from pressure and flow data, was extremely high during voiding efforts. A urethral transitional cell carcinoma along with secondary infection, inflammation, and fibrosis were found to be responsible for the dog's problem. Ability to urinate was restored following removal of the affected portion of the urethra. In a 6-year-old spayed female Doberman Pinscher with urinary incontinence during sleep, a micturition study demonstrated urethral incompetence. During infusion of 0.9% NaCl solution into the bladder, the fluid flowed through the urethra before the detrusor muscle contracted, and urethral resistance during voiding was low. The dog's incontinence was responsive to estrogen administration.

Primary urethral tumors in dogs.

In a review of cases of neoplasia in dogs seen at The Animal Medical Center during a 6-year period, 20 cases of primary urethral tumors were found. The majority of these cases were in older dogs (av abe, 10.4 years) and females (18/20). The most common clinical signs were hematuria and stranguria. Nineteen of the 20 tumors were diagnosed clinically, and the most consistent and useful diagnostic method was pneumocystography-cystography, with voiding urethrography. Of the 5 tumor types (squamous cell carcinoma, transitional cell carcinoma, adenocarcinoma, hemangiosarcoma, and embryonic rhabdomyosarcoma), squamous cell carcinoma was the most common (12/20). Metastasis occurred in 6 of the 20 dogs. Because of metastasis to regional lymph nodes and diffuse extent of the tumor in the urethra in many of the dogs, a caudal abdominal approach for surgical excision is recommended if treatment is attempted.