Surgical treatment of canine urethral prolapse via urethropexy or resection and anastomosis.

OBJECTIVES: The objective was to report and compare the complications and recurrence rates of urethral prolapse in dogs when treated with urethropexy, resection and anastomosis or a combined surgical technique. STUDY DESIGN: Retrospective study. MATERIALS AND METHODS: A total of 86 dogs were identified from the medical records of 10 veterinary referral hospitals from February 2012 and October 2022. Dogs were included if they underwent surgery for a urethral prolapse at first presentation. Complications were classified as minor or major based on the necessity of further surgical intervention. Complications leading to death were also considered major complications. RESULTS: Seventy-nine dogs were included, urethropexy (n=44), resection and anastomosis (n=27) and a combined surgical technique (n=8). Minor complications were identified in 41 of 79 dogs (51.9%): urethropexy 19 of 44 (43.2%), resection and anastomosis 18 of 27 (66.6%) and a combined surgical technique four of eight (50%). Major complications occurred in 23 dogs (29.1%), of which 21 were recurrence (26.6%). Recurrence occurred in 17 of 44 dogs following a urethropexy (38.6%), three of 27 dogs following resection and anastomosis (11.1%) and one of eight dogs treated with a combined surgical technique (12.5%). Recurrence of a urethral prolapse was significantly more likely following urethropexy in comparison to resection and anastomosis. CLINICAL SIGNIFICANCE: Resection and anastomosis was associated with a lower recurrence rate in comparison to urethropexy for the surgical treatment of urethral prolapse. Based on these results, we concluded that resection and anastomosis may be preferable to urethropexy for treatment of urethral prolapse at first presentation. Urethropexy, and resection and anastomosis combined surgical technique was associated with low recurrence rate; however, further studies will be needed to clarify if it provides any benefit over resection and anastomosis.

Intraurethral co-transplantation of bone marrow mesenchymal stem cells and muscle-derived cells improves the urethral closure.

BACKGROUND: Cell therapy constitutes an attractive alternative to treat stress urinary incontinence. Although promising results have been demonstrated in this field, the procedure requires further optimization. The most commonly proposed cell types for intraurethral injections are muscle derived cells (MDCs) and mesenchymal stem/stromal cell (MSCs). The aim of this study was to evaluate the effects of MDC-MSC co-transplantation into the urethra. METHODS: Autologous transplantation of labeled MDCs, bone marrow MSCs or co-transplantation of MDC-MSC were performed in aged multiparous female goats (n = 6 in each group). The mean number of cells injected per animal was 29.6 × 106(± 4.3 × 106). PBS-injected animals constituted the control group (n = 5). Each animal underwent urethral pressure profile (UPP) measurements before and after the injection procedure. The maximal urethral closure pressure (MUCP) and functional area (FA) of UPPs were calculated. The urethras were collected at the 28th or the 84th day after transplantation. The marker fluorochrome (DID) was visualized and quantified using in vivo imaging system in whole explants. Myogenic differentiation of the graft was immunohistochemically evaluated. RESULTS: The grafted cells were identified in all urethras collected at day 28 regardless of injected cell type. At this time point the strongest DID-derived signal (normalized to the number of injected cells) was noted in the co-transplanted group. There was a distinct decline in signal intensity between day 28 and day 84 in all types of transplantation. Both MSCs and MDCs contributed to striated muscle formation if transplanted directly to the external urethral sphincter. In the MSC group those events were rare. If cells were injected into the submucosal region they remained undifferentiated usually packed in clearly distinguishable depots. The mean increase in MUCP after transplantation in comparison to the pre-transplantation state in the MDC, MSC and MDC-MSC groups was 12.3% (± 11.2%, not significant (ns)), 8.2% (± 9.6%, ns) and 24.1% (± 3.1%, p = 0.02), respectively. The mean increase in FA after transplantation in the MDC, MSC and MDC-MSC groups amounted to 17.8% (± 15.4%, ns), 15.2% (± 12.9%, ns) and 17.8% (± 2.5%, p = 0.04), respectively. CONCLUSIONS: The results suggest that MDC-MSC co-transplantation provides a greater chance of improvement in urethral closure than transplantation of each population alone.

Sulforaphane Treatment of Stress Urinary Incontinence Via the Nrf2-ARE Pathway in a Rat Model.

BACKGROUND/AIMS: To explore the effect of sulforaphane (SFN) treatment in rats through the induction of Stress Urinary Incontinence (SUI) via the Nrf2-ARE pathway. METHODS: A total of 18 female rats (Sprague-Dawley) were assigned to three groups: a control group, an SUI group, and an SUI+SFN group (six rats per group). Rats in the treatment groups were induced via postpartum vaginal balloon dilation and bilateral ovariectomy. Rats in the SUI+SFN group were treated via intraperitoneal injection once per day for a total of one month. Urethral sphincter muscle histological was observed by HE and Masson staining. Peak voiding pressure and interval of micturition were measured by cystometry. Oxidative stress markers and protein expression in the Nrf2-ARE pathway were examined by immunohistochemical staining and western blotting. RESULTS: Prolonged micturition interval and higher peak voiding pressure were observed in the SUI+SFN group. Disturbance of muscle morphology was ameliorated, muscle content was elevated, and collagen content was restrained in response to SFN treatment. The SOD, GSH-Px, and CAT activities were elevated in the SUI+SFN group compared to those in the control group. The level of cell apoptosis was decreased in SUI rats after SFN treatment; however, apoptosis was mainly located in the urethral mucosa instead of the muscle layer. SFN reduced the Bax/Bcl-2 expression ratio. Nrf2 and Nrf2 target antioxidant proteins were elevated in the SFN group. CONCLUSIONS: SFN was effective for SUI treatment via decreasing oxidative stress and activating the Nrf2-ARE pathway.

MicroRNA-214 Affects Fibroblast Differentiation of Adipose-Derived Mesenchymal Stem Cells by Targeting Mitofusin-2 during Pelvic Floor Dysfunction in SD Rats with Birth Trauma.

BACKGROUND/AIMS: This study investigated whether microRNA-214 (miR-214) targets mitofusin-2 (Mfn2) in the process of fibroblast differentiation of adipose-derived mesenchymal stem cells (ADMSCs) during pelvic floor dysfunction (PFD) in Sprague Dawley (SD) rats with birth trauma. METHODS: The ADMSCs were isolated from 4-6 week male SD rats (n = 20) and were cultured and divided into the blank, miR-214 mimic negative control (NC), miR-214 mimic, miR-214 inhibitor NC, miR-214 inhibitor, empty vector, Mfn2 over-expression and miR-214 + Mfn2 over-expression groups. Fibroblast differentiation of ADMSCs was measured with immunocytochemistry and immunofluorescence methods. The expression of miR-214 and the mRNA and protein expression of Mfn2, FSP1, Collagen I, Collagen III, Elastin, LOX, Fibulin-5, PPAR-γ and Runx2 were detected using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting, respectively. A dual-luciferase reporter assay was performed to confirm whether Mfn2 was the target gene of miR-214. RESULTS: During ADMSC differentiation into fibroblasts, miR-214 expression was up-regulated, but the expression of Mfn2 was down-regulated. Fibroblast differentiation of ADMSCs was promoted in the miR-214 mimic group but was inhibited in the miR-214 inhibitor and Mfn2 over-expression groups. The expression of Mfn2 was decreased, but the expression of FSP1, Collagen I, Collagen III, Elastin, LOX, Fibulin-5, PPAR-γ or Runx2 was increased in the miR-214 mimic group; the miR-214 inhibitor group and Mfn2 over-expression group exhibited the opposite results. Mfn2 was the target gene of miR-214. CONCLUSIONS: The study provided strong evidence that miR-214 could promote fibroblast differentiation of ADMSCs by down-regulating Mfn2 to improve PFD in SD rats with birth trauma.

A biomimetic mesh for treating female stress urinary incontinence.

For patients with medium to severe incontinence, sub-urethral support surgery has a high cure rate, but using synthetic meshes leads to some complications such as mesh erosion/exposure and thigh pain. Autologous or acellular extracellular matrix grafts present few complications but have a high recurrence rate. Regensling™ is a new sling product made of a synthetic material with a biomimetic structure, aiming to provide long-term mechanical support with a lower complication rate. To assess the safety and effectiveness of Regensling™, both in vitro and in vivo experiments were performed. The mesh was implanted in the subcutaneous, intramuscular and sub-urethral regions of rabbits. At 4, 12, and 26 weeks post-implantation, the animals were executed and the implants were studied for their mechanical and biocompatible properties. Compared to the control material, the Regensling™ was covered by a thin layer of fibrous tissue with good compliance, and had a milder inflammatory response. During the period of the experiment, Regensling™ showed stable strength with an increasing trend over time.

Acquired urinary incontinence in the bitch: update and perspectives from human medicine. Part 3: The urethral component and surgical treatment.

Urethral sphincter mechanism incompetence (USMI) is the most common cause of urinary incontinence in dogs. Surgery may be recommended if the animal does not respond to medical treatment or becomes refractory. In this third part of a three-part review, surgical options for the treatment of USMI are described. Colposuspension is the most frequently described procedure and offers a fair prognosis, with about 50% of the dogs being continent after surgery and most of the reminder being improved or more responsive to medical treatment. Urethropexy offers a similar success rate, but with a higher rate of complications. Endoscopic injection of collagen is an attractive technique due to its minimally invasive nature and low risk of adverse effects. Initial results may however deteriorate with time. Other procedures have been reported, but involve a low number of cases and have resulted in variable success rates. In women, stress urinary incontinence is mainly treated by minimally invasive procedures involving vaginal placement of sub-urethral slings.

Evaluation of phenylpropanolamine in the treatment of urethral sphincter mechanism incompetence in the bitch.

In a multicentre, blinded, placebo-controlled trial, 50 dogs were treated for 28 days with either phenylpropanolamine or a placebo control. Each was given at a dose of one drop per 2 kg orally three times daily, equivalent to 1 mg/kg three times daily of phenylpropanolamine. Dogs that presented with clinical signs consistent with urinary sphincter mechanism incontinence were included in the study. They were examined on three occasions by the investigating veterinary surgeon. The frequency and volume of unconscious urination were scored by veterinary surgeons according to a pre-established scoring system. Phenylpropanolamine proved to be more effective than the placebo in regard to several parameters. At day 28, 85.7 per cent of phenylpropanolamine-treated cases had no episodes of unconscious urination compared with 33.3 per cent of placebo-treated cases. This was statistically significant. Few, mild side effects were seen in either group.

Management of urethral sphincter mechanism incompetence in a male dog with laparoscopic-guided deferentopexy.

Urethral sphincter mechanism incompetence is uncommon in the male dog. Diagnosis is made on the basis of the history (full bladder intermittent incontinence with persistence of normal micturitions), clinical examination and by exclusion of other causes of incontinence, such as prostatic disease, lower urinary tract abnormalities and cystitis. This report describes a case in an 11-year-old male poodle in which positive contrast urethrocystography showed no anatomical abnormalities. Surgical treatment by fixation of both ductus deferens to the abdominal wall under laparoscopic guidance with cranial displacement of the urinary bladder improved the incontinence.

Comparison of stressed simultaneous urethral pressure profiles between anesthetized continent and incontinent bitches with urethral sphincter mechanism incompetence.

The popular urodynamic technique of stressed urethral pressure profilometry used for investigation of genuine stress incontinence in women was adapted and applied to bitches. The aim was to assess the suitability and reproducibility of the technique in the canine species, and to determine whether differences seen in continent and incontinent women were found in bitches. Resting and stressed simultaneous urethral pressure profiles were obtained for 25 continent and 25 incontinent bitches, the latter diagnosed as having urethral sphincter mechanism incompetence. The stressed urethral pressure profiles were produced by ballottement of the abdomen during catheter withdrawal. The degree of stress induced was consistent and had got short-term reproducibility. Highly significant (P < 0.001) differences in the percentage of negative spikes extending below the resting intravesical pressure were found between continent and incontinent bitches. Significant differences were not observed in the pressure transmission profiles between continent and incontinent bitches; both groups had a gradual decrease in pressure transmission from the bladder neck to the external urethral orifice. The distance from the start of the urethral pressure profile to the first negative peak (attributable to respiration or ballottement) on the subtracted profile was compared with the radiographic distance that the bladder neck was positioned with respect to the cranial pubic brim, taking body weight and continence status into account. Body weight and continence status did not have significant effect on the relation in either instance.(ABSTRACT TRUNCATED AT 250 WORDS)