[Pelvic Reconstruction in Abdominal Trachelectomy and Bilateral Salpingo-Oophorectomy for Occult Uterine Endometrial Cancer Found in Specimens Removed in the Context of Laparoscopic Sacrocolpopexy].

In the patients undergoing pelvic organ prolapse (POP) repairs, the incidence of occult uterine endometrial cancer is low and there is no established management procedure for preoperative cancer screening. We report a case of pelvic reconstruction in abdominal trachelectomy and bilateral salpingo-oophorectomy for occult uterine endometrial cancer found in specimens removed in the context of laparoscopic sacrocolpopexy (LSC). A 70-year-old woman presented to our center with cystocele. She underwent LSC and laparoscopic supracervical hysterectomy. She had no atypical genital bleeding; and, transvaginal ultrasound, pelvic plane magnetic resonance imaging and cervical cytology showed no evidence of malignancy. However, the pathological examination showed uterine endometrial cancer. She underwent trachelectomy, bilateral salpingo-oophorectomy and pelvic lymph node dissection. A part of mesh was removed with a cervical stamp, but the remaining mesh was sewn together. At 5 months after the operation, no recurrence of uterine endometrial cancer and POP was seen.

Medium term anatomical and functional outcomes following modified laparoscopic sacrocolpopexy.

INTRODUCTION AND HYPOTHESIS: We evaluated the anatomical and functional outcomes following modified laparoscopic sacrocolpopexy (LSC) utilizing deep dissection of the vaginal walls and distal mesh fixation at the anterior and posterior compartments. We hypothesized that anatomical and functional outcomes improve after this modified LSC technique. METHODS: This was a retrospective study of all women (n = 240) who underwent LSC for pelvic organ prolapse (POP) from January to December 2017 in a tertiary center. POP-Q staging, validated questionnaires (International Consultation on Incontinence Questionnaire-Short Form [ICIQ-SF] and Pelvic Floor Distress Inventory Questionnaire-Short Form), and uroflowmetry were used to evaluate the anatomical and functional outcomes. Statistical analyses were performed using McNemar test and repeated measures analysis of variance with Fisher's least significant difference post hoc (p < 0.05). RESULTS: The anatomical success rate is 96%, with a prolapse recurrence rate of 3.8% at 3-year follow-up. Bulge symptoms and anatomical compartments were significantly improved after LSC. Clinically, there were significant improvements after LSC in voiding dysfunction and bowel symptoms. Also, there was a significant increase in stress urinary incontinence and non-significant decrease in mixed urinary incontinence and urge urinary incontinence. ICIQ-SF and Colorectal-Anal Distress Inventory 8 scores were significantly lower after LSC, signifying improvement in incontinence and bowel symptoms. CONCLUSION: Our modified LSC technique is safe and effective in restoring level 1 and level 2 supports, without adverse effects on urinary and bowel function. Bladder and bowel symptoms have also been found to keep improving over time.

Laparoscopic repair of vesicovaginal fistula caused by radiation therapy: Use of a perirectal fat interposition graft.

INTRODUCTION: We present a case of laparoscopic repair of vesicovaginal fistula caused by radiation therapy using a perirectal fatty tissue interposition graft. CASE PRESENTATION: A 72-year-old woman was diagnosed with vesicovaginal fistula induced by radiation therapy. Repair of the vesicovaginal fistula was achieved via laparoscopic approach. The fistula was exposed, followed by excision of fistula tract, fine dissection to achieve a traction-free approximation of bladder mucosa, then water-tight closure. An interposition graft derived from the perirectal fat was inserted to reduce the risk of repair failure. The patient did not have the incontinence problem at 1-year follow-up. CONCLUSION: The laparoscopic approach for vesicovaginal fistula repair is minimally invasiveness. Preparation of the interposition graft derived from the perirectal fatty tissue was easy and its mobility to achieve closure of the fistula was acceptable. Thus, this procedure is feasible for the repair of poorly vascularized tissues such as radiation-induced fistulas.

Laparoscopic sacrocolpopexy in a patient with vault prolapse of the sigmoid stump after vaginoplasty in Mayer-Rokitansky-Küster-Hauser syndrome: A case report.

Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is a rare congenital anomaly that results in Müllerian agenesis that affects the uterus and upper two-thirds of the vagina. Sigmoid vaginoplasty is a surgical treatment option; however, vaginal prolapse may result as a complication of the sigmoid neovagina. There are no standards for treatment due to the rarity of this condition. We present the case of a 59-year-old woman with a history of sigmoid vaginoplasty who underwent laparoscopic sacrocolpopexy (LSC) for grade IV sigmoid stump prolapse. The patient had a successful outcome and no evidence of recurrent prolapse. This clinical case reveals the feasibility of LSC as a surgical treatment for sigmoid stump prolapses in patients with MRKH syndrome.

Clinical outcomes after laparoscopic sacrocolpopexy for pelvic organ prolapse: A 3-year follow-up study.

OBJECTIVES: To evaluate the mid-range subjective and objective success rate of laparoscopic sacrocolpopexy. METHODS: Of the 317 women with pelvic organ prolapse who underwent laparoscopic sacrocolpopexy surgery at the same center between January 2013 and March 2015, we assessed 233 patients who were followed up for >3 years. We carried out urogynecological examinations and used questionnaires for the postoperative assessment of the patients. Scoring 0 points on question 3 of the Pelvic Floor Distress Inventory-20 was considered to show subjective success. Objective success was defined as stage 0 or 1 on the Pelvic Organ Prolapse Quantification. RESULTS: The subjective and objective success rates in the third year after surgery were 89.7% (209/233) and 90.6% (211/233), respectively, and those in the first year were 90.6% (211/233) and 91.0% (212/233), respectively. Perioperative complications included bladder injury (0.4%) in one case and vaginal wall injury (0.4%) in one case. Postoperative complications included the incidence of chronic pain (mesh retraction) in one case, which was the only case requiring re-operation due to complications (0.4%); vaginal suture exposure (0.4%) in one case; port-site hernia (0.4%) in one case; and subileus (0.4%) in one case. The complications associated with voiding function included de novo stress urinary incontinence (20.6%) in 48 cases, out of which there were 12 cases of de novo overactive bladder (5.2%) and eight cases required midurethral sling procedures. CONCLUSIONS: Laparoscopic sacrocolpopexy provides a good outcome with a low rate of subjective and objective recurrence and surgical complications.

Transvaginal surgery using self-cut mesh for pelvic organ prolapse: 3-year clinical outcomes.

OBJECTIVES: To evaluate subjective and objective outcomes, complication, recurrence, and reoperation rates after transvaginal mesh surgery for the management of pelvic organ prolapse. METHODS: This was a retrospective analysis of transvaginal mesh surgery carried out using self-cut mesh measuring subjective outcomes using validated questionnaires, and objective outcomes using Pelvic Organ Prolapse Quantification. Patients diagnosed with stage ≥2 pelvic organ prolapse were counseled about all possible surgical options. After thorough explanation about the benefits and risks during transvaginal mesh surgery, patients who gave signed consent were scheduled for surgery and evaluated at 1 and 3 years postoperatively. RESULTS: We included 101 patients who completed a minimum of 3-year follow up. One year and 3-year follow up showed significant improvement both on subjective and objective outcomes. Recurrences were observed in three patients (3%), with one (1%) patient undergoing reoperation. One case (1%) of intraoperative complication (bladder injury) and four cases (4%) of postoperative complications (two mesh exposure, one hematoma and one significant increase in post-voiding residual) were recorded. Overall patients' satisfaction was positive. CONCLUSIONS: Transvaginal mesh surgery using self-cut mesh is associated with significant improvement in both subjective and objective outcomes, offering low recurrence and complication rates, and high patient satisfaction rates. It can be a safe, effective and cost-efficient option not only for recurrence cases, but also as primary management of pelvic organ prolapse using a standardized technique and proper patient selection.

Laparoscopic ventral rectopexy with sacrocolpopexy for coexisting pelvic organ prolapse and external rectal prolapse.

OBJECTIVES: Pelvic organ prolapse (POP) POP is defined as the protrusion of pelvic organs from the vaginal canal. POP often coexists with internal rectal prolapse or external rectal prolapse (ERP). A series of patients with coexisting POP and ERP who underwent laparoscopic ventral rectopexy (LVR) combined with laparoscopic sacrocolpopexy (LSC) are reported here. METHODS: Seven patients underwent LVR and LSC together. Fecal incontinence was assessed by the Fecal Incontinence Severity Index (FISI), constipation was assessed by the Constipation Scoring System (CSS), and urinary incontinence was assessed by the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF). Anatomical disorders were assessed by Pelvic Organ Prolapse Quantification (POP-Q) and defecography. RESULTS: The patients' median age was 81 (60-88) years. The median operative time was 380 (282-430) minutes. The median postoperative hospital stay was 3 (1-5) days. There were no postoperative complications. The FISI, CSS, POP-Q, and defecography findings improved postoperatively; however, the ICIQ-SF deteriorated in 2 of 5 patients. CONCLUSIONS: LVR combined with LSC for coexisting POP and ERP is feasible.

[CLINICAL OUTCOMES OF LAPAROSCOPIC SACROCOLPOPEXY FOR PELVIC ORGAN PROLAPSE: A RETROSPECTIVE ANALYSIS OF 500 CASES FROM A SINGLE INSTITUTION].

(Objectives) Laparoscopic sacrocolpopexy (LSC) is becoming a more popular alternative for pelvic organ prolapse (POP) repair in Japan in the recent years. This study aimed to evaluate the safety and efficacy of LSC. (Patients and methods) This is a retrospective study on all the LSC cases that were performed in Urogynecology center, Kameda Medical Center, Japan from January 2013 to March 2016. Medical records of all the patients were retrieved and details on operating time, estimated blood loss, perioperative complications, anatomical recurrence (postoperative POP-Q stage≥II) rate and reoperation rate were assessed.Our procedure of LSC used two pieces of polypropylene mesh placed on the vesico-vaginal and recto-vaginal space in which the dissection was extended to the level of the bladder neck and levator ani muscle. Subtotal hysterectomy was performed in almost all patients with uterus except in 39 women who chose to preserve their uterus. Additionally, multivariate analysis of risk factors for recurrence-free survival was performed using the Cox regression method. (Results) Five hundred and five patients who were diagnosed as POP (cystocele, rectocele, enterocele, uterine prolapse, vaginal vault prolapse) were included. The mean operating time and estimated blood loss were 236 min and 27.2 ml. There were 2.6% perioperative complication rate and 1.0% severe complication rate (Clavien grade≥IIIa). With a median follow-up of 12 months, anatomical recurrence rate was 8.0%, significant anatomical recurrence (stage≥III) rate was 1.2% and reoperation rate was 1.0%. Preoperative POP-Q stage IV was found as independent risk factors for anatomical recurrence. (Conclusions) The present study demonstrated a relatively low complication rate, low significant anatomical recurrence rate and low reoperation rate. Therefore, LSC is a safe and effective surgical treatment for various types of POP.

Upregulation of arginine vasopressin synthesis in the rat hypothalamus after kainic acid-induced seizures.

We examined the effects of kainic acid (KA)-induced seizures on arginine vasopressin (AVP) gene expression in the paraventricular (PVN) and the supraoptic nuclei (SON) of normal rats using in situ hybridization histochemistry. We also investigated the expression of the AVP-enhanced green fluorescent protein (eGFP) fusion gene after KA-induced seizures in transgenic rats. AVP heteronuclear (hn) RNA levels in the PVN and the SON were significantly increased at 3h and 24h after subcutaneous (s.c.) administration of KA in normal rats. AVP mRNA levels in the PVN and the SON did not change significantly at 3h, 24h and 1 week after s.c. administration of KA in normal rats. In KA-administered transgenic rats, AVP-eGFP fluorescence in the magnocellular and parvocellular divisions of the PVN and the SON were significantly stronger compared to vehicle-administered transgenic rats. By pretreatment with MK-801 (nonselective N-methyl-D-aspartate, NMDA, receptor antagonist), AVP-eGFP transgenic rats after administration of KA did not show preconvulsive symptoms or convulsions and AVP-eGFP fluorescence in the magnocellular and parvocellular divisions of the PVN and the SON of these rats was significantly reduced. These results suggested that KA-induced increases in AVP transcripts and AVP were prevented by MK801 because seizure activity was prevented or reduced.

Complete disruption of all nitric oxide synthase genes causes markedly accelerated renal lesion formation following unilateral ureteral obstruction in mice in vivo.

The role of nitric oxide (NO) derived from all three NO synthases (NOSs) in renal lesion formation remains to be fully elucidated. We addressed this point in mice lacking all NOSs. Renal injury was induced by unilateral ureteral obstruction (UUO). UUO caused significant renal lesion formation (tubular apoptosis, interstitial fibrosis, and glomerulosclerosis) in wild-type, singly, and triply NOS(-/-) mice. However, the extents of renal lesion formation were markedly and most accelerated in the triply NOS(-/-) genotype. UUO also elicited the infiltration of inflammatory macrophages, up-regulation of transforming growth factor (TGF)-ß1, and induction of epithelial mesenchymal transition (EMT) in all of the genotypes; however, the extents were again largest by far in the triply NOS(-/-) genotype. Importantly, long-term treatment with the angiotensin II type 1 (AT(1))-receptor blocker olmesartan significantly prevented the exacerbation of those renal structural changes after UUO in the triply NOS(-/-) genotype, along with amelioration of the macrophage infiltration, TGF-ß1 levels, and EMT. These results provide the first evidence that the complete disruption of all NOS genes results in markedly accelerated renal lesion formation in response to UUO in mice in vivo through the AT(1)-receptor pathway, demonstrating the critical renoprotective role of all NOSs-derived NO against pathological renal remodeling.

Involvement of orexin-A on micturition reflex in normal and cyclophosphamide-induced cystitis bladder in rat.

The purpose of the present study was to investigate the effect of orexin-A in the spinal cord on bladder function in normal rats and cyclophosphamide (CYP)-induced cystitis rat models. The effects of intrathecal (i.t.) injection of orexin-A (0.01, 0.1 and 1.0 nmol) on bladder function were examined during continuous infusion cystometrogram (CMG) in urethane anesthetized normal and CYP-induced cystitis rats. The effects of i.t. injection of selective orexin-1 receptor (OXR1) antagonist SB334867 (10 nmol) on orexin-A-induced bladder overactivity in normal rats and SB334867 (10 and 30 nmol) on changes in bladder function in normal and CYP-induced cystitis rats were investigated. The effects of intravenous (i.v.) injection of orexin-A (0.3 and 1.0 nmol) on micturition reflex were also investigated in normal rats. I.t. injection of orexin-A (0.1 and 1.0 nmol) significantly decreased the intercontraction intervals (ICI) in normal and CYP-induced cystitis rats. I.t. injection of SB334867 (10 nmol) significantly increased the ICI of orexin-A induced overactive bladder in normal rats and i.t. injection of SB334867 (30 nmol) also increased the ICI in normal rat bladder. However, in CYP-injected cystitis rat models, i.t. injection of SB334867 did not change the bladder function. I.v. injection of orexin-A failed to affect the bladder function in normal rats. Orexin mRNA levels in the lateral hypothalamus were significantly decreased in CYP-induced cystitis rats. These results indicate that orexin-A in the spinal cord activates micturition reflex via OXR1 in normal rats. In addition, OXR1 antagonist did not have any effect on micturition reflex in CYP-induced cystitis rats.

Effect of ER-beta gene disruption on estrogenic regulation of anxiety in female mice.

It has been shown that long-term estrogen treatment in gonadectomized female mice increases anxiety levels. On the other hand, a recent study has reported that estrogen may down-regulate the levels of anxiety by acting through estrogen receptor (ER) beta. In the present study, we investigated the role of ER-beta in the regulation of anxiety levels in female mice after long-term estrogen treatment. Gonadectomized ER-beta knockout (betaERKO) female mice and their wild type (betaWT) littermates were implanted several different doses (experiment 1: 2.0 microg/day, experiment 2: 1.0, 0.4, 0.2 or 0.1 microg/day) of an estradiol benzoate (EB) or placebo pellet. Ten days after pellet implant, behavioral tests commenced to measure the anxiety levels (experiment 1: light-dark transition test (LDT), experiment 2: LDT, elevated plus maze test (EPM) and social investigation test (SIT)). We found that, at higher-doses, long-term treatment of EB had anxiogenic effects in both betaWT and betaERKO mice as indicated by a decrease of the time spent in the light side and the number of transitions between two sides during LDT. In contrast, several behavioral measurements indicated that the lower-doses treatment of EB might reduce the anxiety levels possibly through ER-beta. Particularly, the anxiolytic effects of EB in the SIT were more pronounced in betaWT mice than betaERKO mice. Together, the findings in the present study suggest that estrogen may have both anxiolytic and anxiogenic effects in female mice, and that ER-beta gene disruption did not affect anxiogenic regulation by estrogen in female mice, but partially affected anxiolytic regulation.

Effect of eviprostat on bladder overactivity in an experimental cystitis rat model.

OBJECTIVE: The purpose of this study was to investigate the effects of eviprostat, a phytotherapeutic drug, on bladder overactivity and inflammation in a cyclophosphamide (CYP)-induced cystitis rat model. METHODS: Female Sprague-Dawley rats received a single intraperitoneal injection of CYP (200 mg/kg) or saline. After the CYP injection, eviprostat (9, 18 or 54 mg/kg per day) or a vehicle was orally given twice each day. Four days after the CYP injection, bladder function was evaluated by cystometrograms under urethane anesthesia. In a separate group, bladder inflammation was compared between the eviprostat- or vehicle-treated animals. Furthermore, the effects of eviprostat on carbachol-induced muscle contraction were evaluated by an in vitro experiment. RESULTS: The intercontraction interval (ICI) significantly decreased in the CYP-injected rats in comparison to the saline-injected rats. In the CYP-injected group, 18 and 54 mg/kg per day of eviprostat treatment significantly increased the ICI, but did not change the maximum voiding pressure in comparison to the vehicle treatment. In the saline-injected group, no significant changes of any parameters in the cystometrograms were observed between the eviprostat- and vehicle-treated groups. CYP-induced bladder inflammation tended to be lower in the eviprostat-treated group in comparison to the vehicle-treated group. An in vitro experiment revealed that eviprostat failed to inhibit carbachol-induced muscle contraction. CONCLUSION: The oral administration of eviprostat suppressed CYP-induced bladder overactivity. The effects of eviprostat on the micturition reflex may be irrespective of antimuscarinic action. The present findings raise the possibility that eviprostat could be an effective treatment for bladder overactivity associated with inflammation.

Thalamic neural activation in the cyclophosphamide-induced visceral pain model in mice.

The afferent nociceptive information from the lower urinary tract terminates in the dorsal horn of the spinal cord, and then projects to the thalamus. In the present study, we examined the effects of visceral nociception from the lower urinary tract on the neural activity of thalamic neurons using cyclophosphamide (CP)-induced cystitis, a model of visceral nociception. The levels of c-fos mRNA as well as protein, a marker of neural activation, were investigated in the thalamus using in situ hybridization histochemistry and immunohistochemistry. The effects of pretreatment with capsaicin were also examined. In the CP-treated group, the c-fos mRNA as well as protein was significantly induced predominantly in the paraventricular area of the thalamus. The induction of c-fos mRNA exhibited a dose-dependency. The induction of c-fos mRNA of CP-treated mice was significantly inhibited by capsaicin pretreatment to deplete C-fibers. Our results indicate that visceral nociception from the lower urinary tract activates thalamic neurons and this activation is mediated in part through the activation of the capsaicin-sensitive C-fiber afferents. The present findings suggest that the levels of c-fos in the paraventricular area of the thalamus may be a useful marker for evaluating the afferent nerve activity from the lower urinary tract.

An angiotensin II receptor blocker increases sexual behavior in type 2 diabetic mice.

The present study was conducted to examine the effects of olmersartan, angiotensin (ANG) II type 1 (AT(1)) receptor antagonist, on the sexual function in type 2 diabetes model mice. Twenty-week-old KK/Ta mice were used as a model of type 2 diabetes. Age-matched ICR and BALB/C mice were used as non-diabetic controls. The animals were fed powder chow either with or without olmesartan (7.5 microg/g in chow) for 4 weeks. The levels of sexual behavior, activity, and anxiety were then examined between the groups treated with and without olmesartan. The KK/Ta mice treated with olmesartan exhibited a significant increase in the number of mounts and intromission and a decrease in the latency to the first mount in comparison to the KK/Ta mice treated without olmesartan. These effects of olmesartan were not observed in the non-diabetic BALB/C and ICR mice. In addition, the olmesartan treatment did not affect the activity and anxiety regardless of the mouse strain. These findings suggest that the interaction between ANG II and AT(1) receptor may be involved in the pathogenesis of the sexual dysfunction associated with type 2 diabetes and a blockade of ANG II may therefore be a potentially useful treatment for male sexual dysfunction in type 2 diabetes.

Up-regulation of galanin and corticotropin-releasing hormone mRNAs in the key hypothalamic and amygdaloid nuclei in a mouse model of visceral pain.

Cyclophosphamide (CP)-induced cystitis is often used as an animal model of visceral pain. Various neuropeptides in the hypothalamic and amygdaloid nuclei are implicated in pain-induced responses. However, little information is available regarding the regulation of the neuropeptides in response to visceral pain. In the present study, we examined the effects of CP-induced cystitis on the levels of mRNAs encoding galanin, corticotropin-releasing hormone (CRH), substance P, and enkephalins in the hypothalamic and limbic nuclei using in situ hybridization histochemistry in mouse. Galanin mRNA levels in CP-treated group increased significantly in the arcuate nucleus and the paraventricular nucleus (PVN) but not in the medial preoptic area after the intraperitoneal administration of CP (200 mg/kg body weight) in comparison to those in saline-treated group. CRH mRNA levels in CP-treated group also increased significantly in the central amygdala as well as the PVN after the CP administration. In contrast, CP-induced cystitis failed to upregulate the preprotachykinin-A and preproenkephalin genes which encode substance P and enkephalins, respectively in the hypothalamic and limbic nuclei at any of the time points examined. These results suggest that visceral nociception may upregulate both galanin and CRH gene expression in the hypothalamic and limbic nuclei.

Prostate cancer cells increase androgen sensitivity by increase in nuclear androgen receptor and androgen receptor coactivators; a possible mechanism of hormone-resistance of prostate cancer cells.

Although androgen-hypersensitivity is one of the possible pathways of hormone-resistance in prostate cancer, the mechanisms of androgen-hypersensitivity are still largely unknown. Using androgen-hypersensitive prostate cancer cells LN-TR2, established from androgen-sensitive LNCaP cells by the long term treatment with tumor necrosis factor alpha, we explored the mechanisms of androgen-hypersensitivity in prostate cancer cells which may thus play a role in hormone-resistance. We examined the androgen receptor (AR) DNA sequence and the expression levels of AR and 8 AR cofactors in LNCaP and LN-TR2 cells. As a result, no novel mutation was developed in AR DNA in LN-TR2 cells. We observed higher expressions of nuclear AR upon androgen-treatment and 2 AR coactivators, ARA55 and TIF2, in LN-TR2 compared to LNCaP cells. An overexpression of ARA55 or TIF2 enhanced androgen-induced AR transcriptional activity in LNCaP cell. In the presence of those AR coactivators, AR activity was observed even at low concentrations of androgen. In 2 of 6 patients, the expression level of ARA55 was higher in cancer cells in hormone-resistant tumor than those in hormone-sensitive tumor. Taken together, our results suggest that prostate cancer cells change androgen-sensitivity by an overexpression of nuclear AR and AR coactivators, thus, resulting in transition from androgen-dependent to androgen-independent prostate cancer cells. An increase in nuclear AR and AR coactivators may cause androgen-hypersensitivity of prostate cancer cells and thus play a role in hormone-resistance, at least in some patients with prostate cancer.

Up-regulation of interleukin-6 gene expression in cyclophosphamide-induced cystitis in mice: An in situ hybridization histochemical study.

AIM: To determine the time course and the cellular sources of interleukin (IL)-6 in the bladder during experimental cystitis, the expression of the IL-6 gene and IL-6 protein was examined in the bladder during cyclophosphamide (CP)-induced cystitis. METHODS: Mice were killed at 0, 1, 2, 6, 12 and 48 h after the intraperitoneal administration of 0.9% saline containing either CP (200 mg/kg) or saline. The expression of IL-6 gene and IL-6 protein were detected using in situ hybridization histochemistry and immunocytochemistry, respectively. RESULTS: In situ hybridization histochemistry showed that IL-6 gene expression was significantly up-regulated in the bladder at 1 h in comparison to that at 0 h after CP administration. The levels of IL-6 gene expression peaked at 6 h after CP administration and then declined thereafter. In contrast, only a few IL-6 transcripts were expressed in the bladder but they remained unchanged following the administration of saline at all time points examined. The IL-6 transcripts were predominantly distributed in the perivascular area of the submucosal layers during CP-induced cystitis. Immunocytochemistry demonstrated IL-6 immunoreactivity in the spindle-shaped cells located in the vicinity of the dilated vessels of the submucosal layers during CP-induced cystitis. CONCLUSION: IL-6 gene expression was up-regulated in the submucosal layer of the bladder and peaked at 6 h after CP administration, suggesting that the primary source of IL-6 may be fibroblasts in the bladder during CP-induced cystitis.