Naoki Kawamorita

Radical prostatectomy for high-risk prostate cancer: Biochemical outcome

Objectives:  To determine the biochemical outcome following radical prostatectomy alone in patients with high‐risk prostate cancer.

Intravesical Liposome and Antisense Treatment for Detrusor Overactivity and Interstitial Cystitis/Painful Bladder Syndrome

Purpose. The following review focuses on the recent advancements in intravesical drug delivery, which brings added benefit to the therapy of detrusor overactivity and interstitial cystitis/painful bladder syndrome (IC/PBS). Results. Intravesical route is a preferred route of administration for restricting the action of extremely potent drugs like DMSO for patients of interstitial cystitis/painful bladder syndrome (IC/PBS) and botulinum toxin for detrusor overactivity. Patients who are either refractory to oral treatment or need to mitigate the adverse effects encountered with conventional routes of administration also chose this route. Its usefulness in some cases can be limited by vehicle (carrier) toxicity or short duration of action. Efforts have been underway to overcome these limitations by developing liposome platform for intravesical delivery of biotechnological products including antisense oligonucleotides. Conclusions. Adoption of forward-thinking approaches can achieve advancements in drug delivery systems targeted to future improvement in pharmacotherapy of bladder diseases. Latest developments in the field of nanotechnology can bring this mode of therapy from second line of treatment for refractory cases to the forefront of disease management.

Intravesical liposome therapy for interstitial cystitis

Over the past two decades, there has been lot of interest in the use of liposomes as lipid‐based biocompatible carriers for drugs administered by the intravesical route. The lipidic bilayer structure of liposomes facilitates their adherence to the apical membrane surface of luminal cells in the bladder, and their vesicular shape allows them to co‐opt the endocytosis machinery for bladder uptake after instillation. Liposomes have been shown to enhance the penetration of both water‐soluble and insoluble drugs, toxins, and oligonucleotides across the bladder epithelium. Empty liposomes composed entirely of the endogenous phospholipid, sphingomyelin, could counter mucosal inflammation and promote wound healing in patients suffering from interstitial cystitis. Recent clinical studies have tested multilamellar liposomes composed entirely of sphingomyelin as a novel intravesical therapy for interstitial cystitis. In addition, liposomes have been used as a delivery platform for the instillation of botulinum toxin in overactive bladder patients. The present review discusses the properties of liposomes that are important for their intrinsic therapeutic effect, summarizes the recently completed clinical studies with intravesical liposomes and covers the latest developments in this field.

Novel rat model of stress urinary incontinence with a retroflexed bladder.

Introduction and hypothesisWe created a rat model with a retroflexed bladder that mimicked the loss of the posterior urethrovesical angle and compared the results with sham-surgery rats for the establishment of rat models of stress urinary incontinence.MethodsThe retroflexed bladder was created by stitching the bladder posteriorly to the psoas muscle. Sneeze-induced urethral pressure response and urethral baseline pressure were measured using a microtip-transducer catheter and leak point pressures induced by sneezing, the Crede maneuver, and the vertical tilt table method were measured via a supra-pubic cystostomy.ResultsIn rats with a retroflexed bladder, both urethral pressure response and sneeze-induced leak point pressure were significantly decreased.ConclusionA retroflexed bladder may cause stress urinary incontinence by attenuating the sneeze-induced active urethral closure mechanism. Urethral pressure response restored by resumption of the posterior urethrovesical angle would explain why no sling tension is needed to treat the stress urinary incontinence.

Surgical and Patient Reported Outcomes of Artificial Urinary Sphincter Implantation: A Multicenter, Prospective, Observational Study

Purpose We performed a multicenter, prospective, observational study to assess outcomes, including changes in continence status and quality of life, after artificial urinary sphincter implantation. Materials and Methods Prospectively enrolled in this study were 135 patients who underwent primary AMS 800™ implantation between 2011 and 2014 at 1 of 5 institutions. Perioperative complications were categorized according to the Clavien‐Dindo classification. We estimated the revision‐free rate, that is the incidence of patients who did not undergo artificial urinary sphincter revision surgery. Cox regression analysis was performed to identify patient risk factors for revision surgery. The number of pads needed per day, ICIQ‐SF (International Consultation on Incontinence Questionnaire‐Short Form) and KHQ (King’s Health Questionnaire) were used to estimate continence status and quality of life preoperatively, and 1, 3 and 12 months postoperatively. Results The artificial urinary sphincter was implanted without major complications. The revision‐free rate 1, 2 and 3 years after implantation was 94%, 88% and 81%, respectively. Diabetes mellitus and poor preoperative American Society of Anesthesiologists® physical status were significant risk factors for revision surgery. Continence status and quality of life were markedly improved after surgery. However, ICIQ‐SF and some KHQ items showed slight but significant deterioration at 12 months compared with scores 1 month after surgery. Conclusions Artificial urinary sphincter implantation is a safe and durable procedure that substantially improves patient continence status and quality of life soon after surgery. Our results indicate that patients start to experience slight but noticeable deterioration in continence status and quality of life relatively early (within 1 year) after surgery. This finding might be helpful with appropriately counseling patients who undergo artificial urinary sphincter implantation.

Role of microglia in the spinal cord in colon-to-bladder neural crosstalk in a rat model of colitis.

We investigated whether spinal cord microglia are involved in colon‐to‐bladder neural crosstalk in a rat model of colitis.

Phosphodiesterase type 5 inhibitor administered immediately after radical prostatectomy temporarily increases the need for incontinence pads, but improves final continence status

Purpose To evaluate the effects of phosphodiesterase type 5 inhibitor (PDE5i) on urinary continence recovery after bilateral nerve-sparing radical prostatectomy (BNSRP). Materials and Methods Between 2002 and 2012, 137 of 154 consecutive patients who underwent BNSRP in our institution retrospectively divided into 3 groups that included patients taking PDE5i immediately after surgery (immediate PDE5i group, n=41), patients starting PDE5i at an outpatient clinic after discharge (PDE5i group, n=56), and patients taking no medication (non-PDE5i group, n=40). Using self-administered questionnaires, the proportion of patients who did not require incontinence pads (pad-free patients) was calculated preoperatively and at 1, 3, 6, 12, 18, and 24 months after BNSRP. Severity of incontinence was determined based on the pad numbers and then compared among the 3 groups. Results Proportions of pad-free patients and severity of incontinence initially deteriorated in all of the groups to the lowest values soon after undergoing BNSRP, with gradual improvement noted thereafter. The deterioration was most prominent in the immediate PDE5i group. As compared to the non-PDE5i group, both the PDE5i and immediate PDE5i groups exhibited a better final continence status. Conclusions PDE5i improves final continence status. However, administration of PDE5i immediately after surgery causes a distinct temporary deterioration in urinary incontinence.

Infliximab-Induced Tubulointerstitial Nephritis with Image Findings of Striated Nephrogram in Crohn’s Disease

Tubulointerstitial nephritis is primary injury to renal tubules and interstititum which could be resulting in decreased renal function. The acute and chronic forms are most often due to allergic drug reactions or to infections. Tubulointerstitial nephritis in Crohns disease has rarely been reported. Imaging findings of a striated nephrogram on enhanced computed tomography (CT) could represent the clinical state of tubulointerstitial nephritis. This is the first report of tubulointerstitial nephritis caused by infliximab, monoclonal antibody against human tumor necrosis factor-α, showing striated nephrograms in Crohns disease. The case of a 28-year-old man treated with infliximab for Crohns disease is described. Infliximab was added to his maintenance therapy, and bowel symptoms were stable. The patient presented with a 2-month history of fever and an elevated C-reactive protein after infliximab administration for 4.5 years. Contrast-enhanced CT showed striated nephrograms in both kidneys. Urinalysis showed no abnormal findings. The pathological diagnosis on CT-guided percutaneous renal needle biopsy was drug-induced tubulointerstitial nephritis because of eosinophilic infiltration with neutrophils mainly in the tubulointerstitial areas. The imaging findings of striated nephrogram are important for the diagnosis of tubulointerstitial nephritis. Tubulointerstitial nephritis could be caused by drug-induced inflammation or direct extension of Crohns disease as an extra-interstitial manifestation. The treatment strategies for these two diseases are contradictory to each other and inappropriate treatment could worsen the renal function. Needle biopsy is therefore indispensable for differential diagnosis.

High luteinizing hormone weakens urinary continence mechanisms in association with prostaglandin E2 elevation in a postmenopausal rat model

To explore the role of luteinizing hormone (LH) in the urinary continence mechanism, urethral function was investigated using a postmenopausal rat model with high serum LH concentrations and the postmenopausal rat model given a gonadotropin releasing hormone (GnRH) antagonist to lower LH concentrations.

Life-threatening Hyperkalemia Associated with Axitinib Treatment in Patients with Recurrent Renal Carcinoma

Axitinib has emerged as a promising antineoplastic agent for the treatment of advanced renal cell carcinoma. Although the administration of axitinib was well-tolerated in clinical trials, the real-world safety and tolerability remain unverified. We herein report a patient with metastatic renal cell carcinoma who suddenly developed life-threatening hyperkalemia following the initiation of axitinib treatment. Although hyperkalemia has been reported with an incidence of <10%, acute severe hyperkalemia may be a considerably critical adverse event of axitinib therapy, especially in patients with risk factors for hyperkalemia. An abundance of caution for unusual and unpredictable toxicities is warranted when using axitinib.