Quality of life analysis in bladder pain syndrome/interstitial cystitis: implications for a multimodal integrated treatment.

BACKGROUND: The aim of this study was to evaluate whether there is a higher prevalence of anxiety-depressive disorders in women with BPS/IC (bladder pain syndrome/interstitial cystitis) than in women with chronic non-neoplastic pain with or without fibromyalgia, to examine possible correlations between urological and psychiatric symptoms. METHODS: The patients included in the study were divided into two groups: 1) group 0: patients with an existing diagnosis of BPS/IC. BPS/IC was confirmed by reviewing medical record; group 1+2: patients with chronic non-neoplastic pain, suffering from fibromyalgia or other types of chronic pain (chronic arthralgia or lower back pain). Three questionnaires were administered: PHQ-9 to investigate psychological symptoms, O'Leary Saint (ICSI-ICPI) to investigate urological symptoms in women with BPS/IC and BPI to investigate specifically pain. RESULTS: The survey included 69 patients, 42 patients had a diagnosis of BPS/IC while 27 of them had chronic non-neoplastic pain. The average PHQ-9 Score was 10.3 in BPS/IC group, considered as major depression (score between 10 and 14); the average score of PHQ-9 was 6.9 in group 1+2, as in sub-threshold depression (between 5-9). CONCLUSIONS: The chronic pain of BPS/IC can affect mood more than in other painful conditions, as more than half of this population has a score that identifies depression with the PHQ-9 questionnaire, confirming the hypothesis that the syndrome is associated with a higher prevalence of an anxious-depressive condition.

Adelmidrol + sodium hyaluronate in IC/BPS or conditions associated to chronic urothelial inflammation. A translational study.

Interstitial cystitis/painful bladder syndrome (IC/PBS) is a chronic bladder condition characterized by frequent urination, bladder inflammation and pain. It is a particular challenging disease and a clear unmet medical need in terms of identifying new therapeutic strategies. The aim of study was to evaluate the anti-inflammatory effects of intravesical Vessilen® (a new formulation of 2% adelmidrol (the diethanolamide derivative of azelaic acid) + 0.1% sodium hyaluronate) administration in rodent models of IC/BPS and in IC/BPS patients or other bladder disorders. Acute and chronic animal models of cystitis were induced by a single or repetitive intraperitoneal injections of cyclophosphamide (CYP); patients with IC/BPS or with bladder pain syndrome associated with symptoms of the lower urinary tract treated once weekly by bladder instillation of Vessilen® for 8 weeks. CYP instillation caused macroscopic and histological bladder alterations, inflammatory infiltrates, increased mast cell numbers, bladder pain, increased expression of nitrotyrosine, decreased expression of endothelial tight junction zonula occludens-1. Intravesical Vessilen® treatment was able to ameliorate CYP induced bladder inflammation and pain by inhibiting nuclear factor-κB pathway and inflammatory mediator levels as well as reduced mechanical allodynia and nerve growth factor levels. A significant improvement in quality of life and symptom intensity were evident in patients with IC/BPS or other bladder disorders treated with Vessilen®. Vessilen® could be a new therapeutic approach for human cystitis.

Metastasis of the epididymis and spermatic cord from pancreatic adenocarcinoma: A rare entity. Description of a case and revision of literature.

INTRODUCTION: Metastatic epididymal and spermatic cord adenocarcinoma from epithelial tumors are a rare condition. The most frequent primary cancers are prostate, lung, kidney, gastrointestinal tumors and breast. In literature, there are very low number of cases reporting metastasis from pancreatic cancer to epididymis and spermatic cord. CASE DESCRIPTION: We report a case of 70-years old man with history of left orchiectomy for undescended testicle, who presented to our department with a palpable nodule in the right scrotum. Scrotal ultrasound revealed an inhomogeneous hypoechoic nodule of epididymis and/or spermatic cord. Neoplastic markers showed high levels of CEA (carcinoembryonic antigen) and bHCG (beta Human Chorionic Gonadotropin). The patient underwent right surgical scrotal exploration with orchifunicolectomy. Pathologic examination revealed pathologic tissue showing rare glandular structures. Immunohistochemistry profile was compatible with malign epithelial neoplasm with glandular differentiation. Total body CT-scan revealed pathologic tissue in pancreas between head and body and a suspect pathologic lesion in liver and 18-FDG PET-scan confirmed the pancreatic neoplastic mass and a suspect secondary hepatic lesion. Biopsy of pancreatic pathologic area was positive for ductal pancreatic adenocarcinoma. The patient was sent to oncologic evaluation and started chemotherapy. CONCLUSIONS: Malignancies of epididymis and spermatic cord are rare entities and, in literature, very low number of cases of metastasis from pancreatic carcinoma to epididymis and spermatic cord are described. Early differential diagnosis is fundamental mostly in those patients with age range unusual for testis cancers.

Vaginal metastasis of bladder urothelial carcinoma: Description of a case and revision of literature.

Vaginal metastases from urothelial cancer are a rare entity and in literature, few cases are described. We report a case of a 68 year-old woman with history of bladder urothelial carcinoma underwent to radical cystectomy who came in our department after 5 months for pelvic pain and vaginal bleeding. Objective examination revealed an ulcerative, solid vaginal lesion in the upper vaginal wall. We performed a vaginal biopsy that showed urothelial carcinoma compatible with the primitive bladder cancer. The patient underwent to surgery and was sent to oncological evaluation.

A retrospective comparison between transrectal and transperineal prostate biopsy in the detection of prostate cancer.

BACKGROUND: The aim of this study was to analyze the differences between TRUSguided transrectal prostate biopsy (TR) and transperineal prostate biopsy (TP) in the diagnosis of prostate cancer. The two biopsy methods were evaluated in terms of diagnostic sensitivity and of early and late complications. METHODS: This retrospective study was realized through the review of clinical records of 219 men that received a prostate biopsy between 2004 and 2014. The biopsy was performed because of elevated prostate-specific antigen (PSA), abnormal digital rectal examination findings (DRE), abnormal transrectal ultrasound (TRUS) findings and symptoms due to prostate diseases. The cohort study was subdivided in two groups: 108 patients received a transrectal biopsy between 2004 and 2006 and 111 received a transperineal biopsy between 2007 and 2014. In both groups, first biopsy was performed with 12 cores scheme whereas second or third biopsy were performed with 18 cores scheme; in this study we excluded patients who underwent to biopsies with different number cores to reduce the bias. Both groups were evaluated on the basis of age, total PSA, PSA ratio (F/T), DRE/TRUS findings, presence/absence of low urinary tracts symptoms (LUTS), presence/absence of benign prostatic hyperplasia (BPH), histologic findings of biopsy cores and immediate/postoperative complications. Then, it was evaluated the overall cancer detection rate and the stratified cancer rate on the basis of the previous reported parameters. Finally, we analyzed the early and late complication rate in both groups. U Mann-Whitney test was used to evaluate the quantitative variables and χ2-test or Fisher exact test for qualitative variables. p < 0.05 was considered statistically significant. RESULTS: 66 cancers were detected in 219 patients of the study; 29 cancers were detected in the TP group and 37 in the TR group. There were no statistically significant differences in the overall cancer rate detected in both groups (26.13% e 34.26% respectively; p = 0.190). However, TP biopsy detected more cancers at first biopsy than TR biopsy (89.7% vs 78.4% respectively; p = 0.021). Moreover, TP biopsy detected more cancers in those patients with low cancer suspect (PSA < 4 ng/ml, F/T > 15%, negative TRUS), instead TR biopsy had more sensitivity in detecting cancer in those patients with high cancer suspect (PSA > 10 ng/ml, F/T < 15%, TRUS with abnormal lesions). The presence of BPH did not influence sensitivity in both cases. There were no significant differences in the early complication rate whereas a statistically significant difference was observed in the late complication rate (4% vs 11% in TP and TR biopsy, respectively; p = 0.019). CONCLUSIONS: No statistically significant differences in sensitivity were observed between TP and TR biopsy, but TP biopsy detected more cancers at first time biopsy. Complications rate was lower in the TP group. Therefore, we conclude that the Urologist has the final choice in deciding the most appropriate biopsy technique, considering sensitivity and complications.

A randomized, open-label, multicenter study of the efficacy and safety of intravesical hyaluronic acid and chondroitin sulfate versus dimethyl sulfoxide in women with bladder pain syndrome/interstitial cystitis.

AIMS: Intravesical instillation of hyaluronic acid (HA) plus chondroitin sulfate (CS) in women with bladder pain syndrome/interstitial cystitis (BPS/IC) has shown promising results. This study compared the efficacy, safety, and costs of intravesical HA/CS (Ialuril® , IBSA) to dimethyl sulfoxide (DMSO). METHODS: Randomized, open-label, multicenter study involving 110 women with BPS/IC. The allocation ratio (HA/CS:DMSO) was 2:1. Thirteen weekly instillations of HA (1.6%)/CS (2.0%) or 50% DMSO were given. Patients were evaluated at 3 (end-of-treatment) and 6 months. Primary endpoint was reduction in pain intensity at 6 months by visual analogue scale (VAS) versus baseline. Secondary efficacy measurements were quality of life and economic analyses. RESULTS: A significant reduction in pain intensity was observed at 6 months in both treatment groups versus baseline (P < 0.0001) in the intention-to-treat population. Treatment with HA/CS resulted in a greater reduction in pain intensity at 6 months compared with DMSO for the per-protocol population (mean VAS reduction 44.77 ± 25.07 vs. 28.89 ± 31.14, respectively; P = 0.0186). There were no significant differences between treatment groups in secondary outcomes. At least one adverse event was reported in 14.86% and 30.56% of patients in the HA/CS and DMSO groups, respectively. There were significantly fewer treatment-related adverse events for HA/CS versus DMSO (1.35% vs. 22.22%; P = 0.001). Considering direct healthcare costs, the incremental cost-effectiveness ratio of HA/CS versus DMSO fell between 3735€/quality-adjusted life years (QALY) and 8003€/QALY. CONCLUSIONS: Treatment with HA/CS appears to be as effective as DMSO with a potentially more favorable safety profile. Both treatments increased health-related quality of life, while HA/CS showed a more acceptable cost-effectiveness profile.

Headache, low back pain, other nociceptive and mixed pain conditions in neurorehabilitation. Evidence and recommendations from the Italian Consensus Conference on Pain in Neurorehabilitation.

Pain is a disabling symptom and is often the foremost symptom of conditions for which patients undergo neurorehabilitation. We systematically searched the PubMed and Embase electronic databases for current evidence on the frequency, evolution, predictors, assessment, and pharmacological and non-pharmacological treatment of pain in patients with headache, craniofacial pain, low back pain, failed back surgery syndrome, osteoarticular pain, myofascial pain syndrome, fibromyalgia, and chronic pelvic pain. Despite the heterogeneity of published data, consensus was reached on pain assessment and management of patients with these conditions and on the utility of a multidisciplinary approach to pain therapy that combines the benefits of pharmacological therapy, physiotherapy, neurorehabilitation, and psychotherapy. We of the Italian Consensus Conference on Pain in Neurorehabilitation (ICCPN) suggest a need to conduct randomized controlled trials on the efficacy of pain treatments and their risk-benefit profile for the conditions we have reviewed.

Effect of local estrogen therapy (LET) on urinary and sexual symptoms in premenopausal women with interstitial cystitis/bladder pain syndrome (IC/BPS).

The association between vulvodynia and interstitial cystitis/bladder pain syndrome (IC/BPS), a chronic, debilitating disease of unknown etiology, may involve sex hormone-dependent mechanisms regulating vulvo-vaginal health. We aimed to prospectively investigate the effects of 12 weeks of local estrogen therapy (LET) on urinary/bladder and sexual symptoms in premenopausal women with IC/BPS. Thirty-four women (mean age: 36.1 ± 8.4) diagnosed with IC/BPS were treated vulvo-vaginally three-times/week with estriol 0.5 mg cream and tested by validated questionnaires (ICSI/ICPI, pain urgency frequency [PUF], female sexual function index [FSFI]) and by cotton swab testing, vaginal health index (VHI) and maturation index (MI) before and after treatment. Vulvodynia was present in 94.1% of IC/BPS women. A significant positive effect of LET was evident on urinary and sexual function (p < 0.001, for both) following 12 weeks, as well as an improvement of the VHI (p < 0.001) and the MI (p < 0.04). The results of this open study indicate that 12 weeks of local estriol cream at vaginal and vestibular level may ameliorate urinary/bladder pain symptoms, as well as may improve domains of sexual function. The association between vulvar pain and bladder pain could, therefore, be related to a vaginal environment carrying signs of hypoestrogenism, but further studies are needed to clarify this issue.

Pharmacokinetic considerations for therapies used to treat interstitial cystitis.

INTRODUCTION: Interstitial cystitis (IC) or bladder pain syndrome (BPS) is defined as supra-pubic pain related to bladder filling. IC is characterized by a particular symptom complex with no identifiable causes; as with bladder hypersensitivity it is usually associated with urinary frequency and urgency with bladder pain. No current treatments have a significant impact on symptoms over time. AREAS COVERED: This systematic review examines the pharmacokinetic aspects and adverse event of present IC therapy to highlight appropriate treatment to improve the symptoms of IC. This article reviews material obtained via Medline, PubMed, and EMBASE literature searches up to October 2013. EXPERT OPINION: The correct approach to IC should consider a multidisciplinary team of specialists and a multimodal treatment package that include psychotherapy, behavior change, physical activation, and analgesic treatment. Unfortunately, a single therapeutic target for IC is not yet known. With regard to pathophysiology and therapy, there is more to discover. The first insult damages the bladder urothelium, hence vehicles that lead the drug to penetrate the wall of the bladder might be a novel strategic approach.

Impact of intravesical hyaluronic acid and chondroitin sulfate on bladder pain syndrome/interstitial cystitis.

INTRODUCTION AND HYPOTHESIS: Intravesical instillations of hyaluronic acid (HA) and chondroitin sulfate (CS) may lead to regeneration of the damaged glycosaminoglycan layer in interstitial cystitis/bladder pain syndrome (IC/BPS). METHODS: Twenty-two patients with IC/BPS received intravesical instillations (40 ml) of sodium HA 1.6% and CS 2.0% in 0.9% saline solution (IALURIL, IBSA) once weekly for 8 weeks, then once every 2 weeks for the next 6 months. RESULTS: The score for urgency was reduced from 6.5 to 3.6 (p = 0.0001), with a reduction in pain scores from an average of 5.6 to 3.2 (p = 0.0001). The average urine volume increased from 129.7 to 162 ml (p < 0.0001), with a reduction in the number of voids in 24 h, from 14 to 11.6 (p < 0.0001). The IC Symptom and Problem Index decreased from 25.7 to 20.3 (p < 0.0001), and the Pain Urgency Frequency score, from 18.7 to 12.8 (p < 0.0001). CONCLUSION: The treatment appeared to be effective and well tolerated in IC/BPS in this initial experience.

Interstitial cystitis is associated with vulvodynia and sexual dysfunction--a case-control study.

INTRODUCTION: Dyspareunia and sexual dysfunction are common in women with urological disorders. The study of comorbidity between interstitial cystitis (IC) and vulvodynia seems to be relevant to understand the mechanism generating pain in these conditions. AIM: To conduct a case-control study for evaluating vulvodynia and sexual dysfunction in women with IC. METHODS: Forty-seven women with new diagnosis (National Institutes of Health [NIH]/National Institute of Diabetes and Digestive and Kidney Diseases [NIDDK] Criteria) of IC were compared with 188 age-matched, negative controls. Each woman completed a semi-structured interview and the Female Sexual Function Index (FSFI). A gynecological examination to assess vulvodynia (cotton swab testing) and genital health (vulvoscopy, Pap smear, culture, and vaginal health index score [VHIS]) was performed. MAIN OUTCOME MEASURES: Prevalence of vulvodynia, sexual function, and sociodemographic/gynecological variables significantly associated with IC. RESULTS: Spontaneous or provoked vulvodynia was reported by 23.4% and 74.5% of IC cases, respectively. Sexual function was significantly impaired (median total FSFI score: IC cases 16.85 ± 8.73 vs. controls 27.34 ± 6.41; P<0.0001) in sexually active women, and 23.4% of IC cases as compared to 9% of controls reported no sexual activity in the year preceding the study (χ(2) for trend=38.2, P<0.0001). VHIS was highly impaired in women with IC in comparison with controls (P<0.0001). Variables significantly associated with IC were a diagnosis of menopause (odds ratio [OR]=31.2, 95% confidence interval [CI]=8.1-120.5), past (OR=4.6, 95% CI=1.74-12.1) or current (OR=6.9, 95% CI=2.1-22.1) oral contraceptive use, and a histologically confirmed diagnosis of endometriosis (OR=3.7, 95% CI=1.1-12.7). CONCLUSION: We found an increased prevalence of vulvodynia among women with recently diagnosed IC; both conditions seem to have profound consequences on women's sexual function. A potential role for sex hormone-dependent mechanisms into the comorbidity of vulvar and bladder pain is proposed, but further research is warranted.

Insight into urogynecologic features of women with interstitial cystitis/painful bladder syndrome.

OBJECTIVE: The prevalence of interstitial cystitis/painful bladder syndrome (IC/PBS) among gynecologic patients attending vulvar disease or pelvic pain clinics is higher than expected. The evaluation of gynecologic characteristics in patients with IC/PBS could be important to delineate a better therapeutic strategy. METHODS: We compared clinical gynecologic characteristics including localized and generalized vulvodynia and sexual activity of 47 women with a definite diagnosis of IC/PBS versus 47 negative controls. RESULTS: The prevalence of both generalized or localized vulvodynia was 85.1% (40 of 47) in the patients and 6.4% (3 of 47) in the control group (p<0.0001 by Fisher exact test). The mean visual analogue score on generalized or localized vulvodynia evaluated with the cotton swab test was 6.1+/-2.6 (SD) among women with IC/PBS and 0.6+/-1.7 in the control group (p<0.0001 with Mann-Whitney U test). Pain during intercourse was described as unbearable by 15 women with IC/PBS (31.9%) and 2 controls (4.3%; p=0.001 by Fisher exact test). Sexual function was significantly impaired in women with IC as measured by the median total score of the Female Sexual Function Index in comparison with controls (13.8 vs. 28.7; p<0.0001). CONCLUSIONS: Patients with a definite diagnosis of IC/PBS appear to have a high risk of vulvodynia with the associated negative implications for sexual activity. The establishment of a multidisciplinary approach with the involvement of the gynecologist appears to be a logical requisite for a correct treatment strategy for these patients.

Evaluation of urinary and general symptoms and correlation with other clinical parameters in interstitial cystitis patients.

AIMS: Interstitial cystitis (IC) has been deemed by some authors as a local manifestation of a systemic disease, particularly one of the autoimmune disorders. In order to provide an answer to the question whether IC patients do or do not indiscriminately report high scores for various somatic symptoms, we compared University of Wisconsin scores (U-W scores), including both urinary and non-urinary symptoms, for 30 IC female patients and 30 female controls. MATERIALS AND METHODS: A total of 30 female patients with IC and 30 healthy female controls were recruited for the study. All patients had to meet the symptom criteria established by the National Institute for Diabetes and Digestive and Kidney Diseases. Each patient completed a University of Wisconsin symptom scale, after translation (WICS). RESULTS: In the IC group median score was zero for all, but two of the reference symptoms: abdominal cramps and dizziness. All urinary symptoms were significantly increased in IC patients compared to controls. In the control group, the median value of urinary symptoms was zero. The duration of the disease was then related to IC symptoms in the patient group. Among the bladder-related symptoms, a good correlation was found for several specific symptoms and urinary symptoms as a whole. An association could be found between a positive potassium sensitivity test (PST) and burning bladder sensation, as well as pelvic discomfort. CONCLUSIONS: IC patients had significantly higher scores for the seven urinary symptoms compared to controls. The duration of disease was found to be correlated with the group of seven urinary symptoms.