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.

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.

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.

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.

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.

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.

Recurrent urethral fibroepithelial polyps in a golden retriever.

A 2 yr old castrated male golden retriever was referred multiple times over a period of 7.5 yr for stranguria, pollakiuria, urinary incontinence and urinary outflow obstructions due to urethral polyps. Diagnostic imaging modalities used to identify polyps included abdominal ultrasound, excretory urography, double-contrast retrograde urethrocystograms, and urethrocystoscopy, which revealed multiple filling defects within the proximal and prostatic urethra. Multiple cystotomies and endourologic procedures were performed to remove the multiple fibroepithelial polyps within the proximal and prostatic urethra. Urinary incontinence resulted from treatments, but did respond to phenylpropanolamine. Medical treatment consisted of a nonsteroidal anti-inflammatory drug, which appeared to decrease the recurrence of the polyps over time. Urethral polyps are an uncommon cause of urinary outflow obstruction and do not usually recur after removal. This case illustrates an uncommon clinical presentation and the difficulties encountered in treatment over an expanded time frame.

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.

Evaluation of outcome following urethral stent placement for the treatment of obstructive carcinoma of the urethra in dogs: 42 cases (2004-2008).

OBJECTIVE: To evaluate the outcome following urethral stent placement for the palliative treatment of obstructive carcinoma of the urethra in dogs. DESIGN: Retrospective case series. ANIMALS: 42 dogs with obstructive carcinoma of the urethra. PROCEDURES: Medical records for dogs in which a self-expanding metallic stent (SEMS) was used for the treatment of obstructive carcinoma of the urethra were reviewed. Signalment, diagnostic findings, clinical signs before and after SEMS placement, and patient outcome were analyzed. Fluoroscopic images were evaluated to determine the effects of stent size, obstruction length, tumor length, and urethral length and width on the incidence of incontinence or stranguria. RESULTS: Resolution of urinary tract obstruction was achieved in 41 of 42 (97.6%) dogs. After SEMS placement, 6 of 23 male and 5 of 19 female dogs developed severe incontinence, and 1 of 23 male and 1 of 17 female dogs developed stranguria. Stent length, diameter, and location were not associated with incidence of incontinence or stranguria. Median survival time after SEMS placement was 78 days (range, 7 to 536 days). Treatment with NSAIDs before and chemotherapeutics after SEMS placement increased median survival time to 251 days (range, 8 to 536 days). CONCLUSIONS AND CLINICAL RELEVANCE: Urethral SEMS placement was an effective palliative treatment for dogs with obstructive carcinoma of the urethra; however, severe incontinence subsequently developed in 11 of 42 (26%) treated dogs. Adjunctive treatment of affected dogs with NSAIDs and chemotherapeutics significantly increased the median survival time.

Penile amputation and scrotal urethrostomy in 18 dogs.

The objective of this study was to report the signalment, indications for surgery, postoperative complications and outcome in dogs undergoing penile amputation and scrotal urethrostomy. Medical records of three surgical referral facilities were reviewed for dogs undergoing penile amputation and scrotal urethrostomy between January 2003 and July 2010. Data collected included signalment, presenting signs, indication for penile amputation, surgical technique, postoperative complications and long-term outcome. Eighteen dogs were included in the study. Indications for surgery were treatment of neoplasia (n=6), external or unknown penile trauma (n=4), penile trauma or necrosis associated with urethral obstruction with calculi (n=3), priapism (n=4) and balanoposthitis (n=1). All dogs suffered mild postoperative haemorrhage (posturination and/or spontaneous) from the urethrostomy stoma for up to 21 days (mean 5.5 days). Four dogs had minor complications recorded at suture removal (minor dehiscence (n=1), mild bruising and swelling around the urethrostomy site and mild haemorrhage at suture removal (n=2), and granulation at the edge of stoma (n=1)). One dog had a major complication (wound dehiscence and subsequent stricture of the stoma). Long-term outcome was excellent in all dogs with non-neoplastic disease. Local tumour recurrence and/or metastatic disease occurred within five to 12 months of surgery in two dogs undergoing penile amputation for the treatment of neoplasia. Both dogs were euthanased.

Results of biopsy via transurethral cystoscopy and cystotomy for diagnosis of transitional cell carcinoma of the urinary bladder and urethra in dogs: 92 cases (2003-2008).

OBJECTIVE: To assess the diagnostic utility of transurethral cystoscopic biopsy in dogs with histologically confirmed transitional cell carcinoma (TCC) of the urinary bladder and urethra. DESIGN: Retrospective case series. ANIMALS: 92 dogs with histologically confirmed TCC. PROCEDURES: Information on sex, breed, neuter status, body weight, tumor location, biopsy method, number of biopsy procedures, experience level of clinician performing biopsy, and quality of biopsy sample was obtained from medical records. The association of variables with likelihood of achieving a diagnostic-quality biopsy sample was evaluated by use of logistic regression. RESULTS: If used as the initial biopsy method, cystoscopic biopsy samples were of diagnostic quality in 65% of male dogs and 96% of female dogs with histologically confirmed TCC. Cystoscopic biopsy samples were significantly more likely to be of diagnostic quality in female dogs than in male dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Cystoscopic biopsy is an effective method to obtain biopsy samples in dogs with TCC of the bladder and urethra. Cystoscopy is more likely to produce a diagnostic-quality biopsy sample in female dogs with TCC than in male dogs with TCC. Cystoscopy should be considered as a primary means of biopsy in male and female dogs with masses of the urinary bladder or urethra.

A case report: veterinary palliative care and hospice for a west highland terrier with transitional cell carcinoma.

In providing palliative care and hospice in a veterinary outpatient primary care setting it is important to manage all aspects of the patient's needs as well as the primary disease process, and to understand that veterinary palliative care and hospice do not require a special degree or board certification. They only require compassion for the terminally ill patient and the human family members, a commitment to keeping patients united with their families for as long as they are comfortable, and a willingness to keep a comprehensive perspective on the patient's changing needs as death nears.

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.

Fluoroscopic stent placement for the relief of malignant urethral obstruction in a cat.

The clinical features and interventional therapy in the case of a female cat with urinary tract obstruction secondary to neoplasia are presented. This form of neoplasia in cats is rare and therapeutic intervention to relieve urinary tract obstruction caused by malignancy has been described only once. This is the first report of a self-expandable metallic stent placed in a feline urethra to relieve obstruction caused by malignancy and the first report of the use of a unique composite metallic stent (Platinol™) in a cat. In conclusion, the palliative stenting of the feline urethra may be a valid therapeutic intervention for malignancies. Further studies are required to determine the optimal size and type of stent that will provide the greatest benefit.

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.

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.