Transient ischemic attack after electromotive drug administration for chronic non-infectious cystitis: report of two similar cases

Electromotive drug administration (EMDA) is a new and promising approach for the treatment of chronic non-infectious cystitis. In animal studies utilizing EMDA there was evidence for deep penetration of dyes into the muscular layers of the bladder wall. However, besides minor local irritation no systemic side effects have been reported after translation of EMDA into the clinical setting.AIMS: This article reports for the first time systemic neurological alterations after EMDA for chronic non-infectious cystitis. SUBJECTS AND METHODS: Two male patients, aged 72 and 78 years, respectively, were readmitted to the emergency room within few hours after EMDA showing clinical signs of transient ischemic attacks (TIA). After clinical examination, both patients were observed. RESULTS: Under overnight observation without any specific therapy the symptoms vanished completely in both patients. CONCLUSIONS: In older patients (>70 years of age) undergoing EMDA, cardiac and neurologic function should be monitored. The time of treatment during the first EMDA session should be limited to 15 or 20 min.     

Electromotive drug administration of lidocaine and dexamethasone followed by cystodistension in women with interstitial cystitis

Electromotive drug administration (EMDA) involves the active transport of ionized drugs such as lidocaine by the application of an electric current. Twenty-one female subjects with interstitial cystitis were treated with EMDA of lidocaine and dexamethasone, followed by cystodistension. The procedure was convenient and well tolerated, with hospital attendance for 1 hour. Bladder anesthesia was excellent, with cystodistension from a discomfort level of 200 ml to a mean volume of 600 ml. Eighty-five percent had a good response (reduction in frequency and in pain score by 3 or more) at 2 weeks, with 63% still responding at 2 months. An excellent response (pain score of 0) was present in 25% of patients reviewed at 6 months. These results are comparable to the response following cystodistension under general anesthesia. There is a need for a randomized blinded comparison of lidocaine with and without EMDA. If proven to be of pharmacological efficacy, EMDA would have many applications in facilitating procedures previously requiring general anesthesia. EDITORIAL COMMENT: Electromotive drug administration is a new therapy being evaluated by these researchers for interstitial cystitis. Traditional drugs and hydrodistention are used with the addition of this new modiality. Randomized controlled trials are necessary to see if the initially good results can be confirmed.     

肝素膀胱灌注治疗间质性膀胱炎

目的　观察肝素膀胱灌注治疗间质性膀胱炎的疗效。　方法　 17例间质性膀胱炎患者 ,均为女性。平均年龄 35岁。平均病程 2 7个月。临床表现主要为尿频及膀胱区疼痛。膀胱镜检见黏膜下点状出血 15例 ,Hunner溃疡 2例。按O’Leary Sant间质性膀胱炎症状评分 (ICSI) 8～ 18分 ,平均 (13.4± 3.5 )分 ;问题评分 (ICPI) 3～ 12分 ,平均 (8.2± 3.4 )分。所有患者均使用肝素钠 10 5U膀胱灌注 ,每周 3次 ,疗程 4周。观察治疗后患者症状改善情况。　结果　 17例患者随访 3～ 12个月 ,平均 6个月 ,症状缓解 14例 ,其中症状显著缓解或消失 9例 ,评分下降 7分 ;症状部分缓解 5例 ,评分下降 >3分 ;无效 3例。 2例于治疗 7个月及 9个月症状复发。有效率 82 %。治疗后 1、2个月ICSI分别降至 (6 .1± 3.4 )、(6 .3± 3.5 )分 ,ICPI分别降至 (3.5± 2 .9)、(3.6± 2 .7)分 ,治疗前后比较差异有显著性意义 (P <0 .0 1)。治疗期间发生一过性尿道灼痛者 2例 ,轻微肉眼血尿 1例。　结论　肝素膀胱灌注治疗可有效缓解间质性膀胱炎患者症状 ,提高生活质量。     

膀胱水扩张联合灌注树胶脂毒素治疗间质性膀胱炎的疗效分析

目的 评价使用腰麻下膀胱水扩张联合灌注树胶脂毒素(RTX)治疗间质性膀胱炎(IC)的疗效.方法 回顾性分析16例间质性膀胱炎患者,均使用腰麻下行水扩张加RTX膀胱灌注.评价治疗前、后1个月以及6个月的排尿次数,排尿量以及临床症状比较.结果 所有患者治疗前与治疗后1个月以及6个月的排尿频率、最大膀胱容量以及临床症状评分相...     

阿米替林治疗间质性膀胱炎的临床研究

目的 探讨阿米替林治疗间质性膀胱炎的有效性和安全性. 方法 采用前瞻性研究.间质性膀胱炎患者54例,病程19～72个月,平均(40.7±11.6)个月.口服阿米替林治疗,起始剂量25 mg/次,每晚1次.1周后,若症状不缓解,可加量至50 mg/次;再观察1周,若症状仍不缓解,则可加量至75 mg/次;维持能够缓解症状的最小剂量,总疗程3个月.观察用药前及用药3个月后患者的临床症状(每日排尿次数、最大排尿容量、尿痛程度评分)和O'Leary-Sant间质性膀胱炎问卷表评分及生活质量评分情况.并记录不良反应发生情况. 结果 ①用药3个月后每日排尿次数明显减少,治疗前后分别为(28.5±8.4)和(15.6±3.3)次;最大排尿容量明显增加,治疗前后分别为(108.7±62.2)和(171.0±53.9)ml;尿痛程度评分明显下降,治疗前后分别为6.4±1.5和2.2±1.5,上述指标用药前后相比,差异均有统计学意义(P<0.01).②患者用药3个月后问卷评分和生活质量评分均明显减少,治疗前后分别为26.9±4.0和13.7±5.7及5.5±0.5和2.5±0.6;用药前后比较,差异有统计学意义(P<0.01).③45例在服药第1个月内有不同程度的困倦,43例1个月后自行缓解,2例由于困倦严重且不能缓解而停药.10例服药3个月后体质量增加(5.8±1.8)kg.11例有轻度便秘症状,可以耐受.9例有口干症状,可以耐受.3例出现重度排尿困难,停药后改为其他方法治疗. 结论 阿米替林口服治疗能有效缓解间质性膀胱炎患者的临床症状,改善生活质量,且耐受性及安全性好.     

The effects and effectiveness of electromotive drug administration and chemohyperthermia for treating non-muscle invasive bladder cancer

Introduction

Preliminary studies show that device assisted intravesical therapies appear more effective than passive diffusion intravesical therapy for the treatment of non-muscle invasive bladder cancer (NMIBC) in specific settings, and phase III studies are now being conducted. Consequently, we have undertaken a non-systematic review with the objective of describing the scientific basis and mechanisms of action of electromotive drug administration (EMDA) and chemohyperthermia (CHT).

Methods

PubMed, ClinicalTrials.gov and the Cochrane Library were searched to source evidence for this non-systematic review. Randomised controlled trials, systematic reviews and meta-analyses were evaluated. Publications regarding the scientific basis and mechanisms of action of EMDA and CHT were identified, as well as clinical studies to date.

Results

EMDA takes advantage of three phenomena: iontophoresis, electro-osmosis and electroporation. It has been found to reduce recurrence rates in NMIBC patients and has been proposed as an addition or alternative to bacillus Calmette–Guérin (BCG) therapy in the treatment of high risk NMIBC. CHT improves the efficacy of mitomycin C by three mechanisms: tumour cell cytotoxicity, altered tumour blood flow and localised immune responses. Fewer studies have been conducted with CHT than with EMDA but they have demonstrated utility for increasing disease-free survival, especially in patients who have previously failed BCG therapy.

Conclusions

It is anticipated that EMDA and CHT will play important roles in the management of NMIBC in the future. Techniques of delivery should be standardised, and there is a need for more randomised controlled trials to evaluate the benefits of the treatments alongside quality of life and cost-effectiveness.     

膀胱水扩张联合灌注树胶脂毒素治疗间质性膀胱炎的疗效分析

目的 评价使用腰麻下膀胱水扩张联合灌注树胶脂毒素(RTX)治疗间质性膀胱炎(IC)的疗效.方法 回顾性分析16例间质性膀胱炎患者,均使用腰麻下行水扩张加RTX膀胱灌注.评价治疗前、后1个月以及6个月的排尿次数,排尿量以及临床症状比较.结果 所有患者治疗前与治疗后1个月以及6个月的排尿频率、最大膀胱容量以及临床症状评分相比,均有明显改善差异有统计学意义(P＜0.05).16例患者中14位患者有不同程度的症状改善.2例患者的临床症状消失或明显改善.结论 RTX膀胱灌注以及膀胱水扩张对于间质性膀胱炎是短期内安全有效改善症状的治疗方法.     

Intravesical hyaluronic acid treatment for ketamine-associated cystitis: Preliminary results

IntroductionLong-term ketamine abuse may cause variable lower urinary tract symptoms (LUTS) and severe cystitis. The clinical features of ketamine-associated cystitis (KC) are very similar to bladder pain syndrome/interstitial cystitis (BPS/IC). Intravesical administration of hyaluronic acid (HA) is one of the regimens for treating BPS/IC. In this study, we aim to investigate whether intravesical HA therapy may improve the LUTS of patients with KC.Materials and methodsFour female patients and one male patient with KC who failed oral medications were enrolled in this study. HA (Cystistat) at a dose of 40 mg in a volume of 50 mL of phosphate-buffered saline was injected into the bladder on a weekly basis for 6 weeks and then monthly for a further 3 months. Response to therapy was evaluated by the visual analog scale (VAS) for pain, International Prostate Symptom Score (IPSS), Overactive Bladder Symptom Score (OABSS), O'Leary-Sant Interstitial Cystitis Symptom Index (ICSI), and Interstitial Cystitis Problem Index (ICPI). Treatment efficacy was assessed by comparing the pretreatment and posttreatment mean scores of the five questionnaires using the paired t test.ResultsThe mean age of the patients was 22 ± 1.5 years. The mean duration of ketamine abuse was 68 ± 16.7 months. After intravesical HA therapy for 4 weeks, statistically significant mean decreases in VAS (from 7 to 4.4, p = 0.03), IPSS voiding subscore (from 16.2 to 11.6, p = 0.017), and ICSI (from 16.4 to 13.6, p = 0.016) questionnaire scores were seen. However, only ICSI constantly reduced after 4 weeks of treatment.ConclusionIntravesical HA therapy may have short-term benefits for improving bladder pain and voiding symptoms in patients with KC.     

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.     

Efficacy of oral doxepin and piroxicam treatment for interstitial cystitis

OBJECTIVE: To establish the efficacy of a multidrug oral treatment with the tricyclic antidepressant agent doxepin and the cyclooxygenase (COX) inhibitor piroxicam in patients with interstitial cystitis (IC), who had failed standard therapy in an open, prospective, nonrandomized study. METHODS: A total of 37 patients diagnosed with IC received 75 mg doxepin and 40 mg piroxicam daily. The treatment was termed DOXCAM. Effectiveness of therapy was assessed with frequency-volume charts, an IC symptom score and with cystometry prior to treatment, 8 weeks after the start and 4 weeks after termination of drug treatment. RESULTS: Medication was not tolerated by five patients. Twenty-six of 32 patients have experienced virtual total remission of symptoms (81%) and six patients had significant relief (19%). DOXCAM treatment resulted in a significant percent decrease in pain (65% versus 21%). Daytime frequency decreased from 17.6+/-5.7 to 11.3+/-3.6 voids while nocturia did not improve significantly. Twenty-three of the 26 patients who became symptom free and four of the six patients who showed significant improvement had a return of symptoms after cessation of therapy. CONCLUSION: It is reasonable to consider oral treatment with DOXCAM in those patients who have failed first-line therapies.     

间质性膀胱炎16例的诊断与治疗

目的探讨间质性膀胱炎(IC)的诊断和治疗方法。方法回顾分析16例IC患者的临床资料,患者主要表现为尿频、尿急、耻骨上疼痛和慢性盆腔疼痛,误诊为慢性膀胱炎、盆腔炎、子宫内膜异位症、膀胱结核及尿道综合征,经手术后病理或膀胱镜检查确诊,其中4例行尿流改道,2例行乙状结肠膀胱成形术,10例行药物治疗。结果4例患者行尿流改道治疗后盆腔疼痛完全消失。2例行膀胱成形术后仍有轻微会阴部不适,膀胱容量大于350 m l,分别随访24,33个月无复发。10例非手术治疗患者O′Leary-Sant间质性膀胱炎症状评分和IC问题评分分别由治疗前的(15.4±4.1)和(9.4±2.7)分,降至治疗后的(4.1±2.1)和(5.1±3.9)分。结论对IC的诊断和鉴别诊断应给予充分重视;及早诊断及多种措施联合治疗,可显著改善IC患者的症状,提高生活质量。     

Resiniferatoxin in the treatment of interstitial cystitis: a systematic review

Resiniferatoxin, a treatment based on a physiopathological concept (the involvement of C fibers and transient receptor potential vanilloid 1 in the transmission of pain) is undergoing evaluation for interstitial cystitis. We evaluated the current evidence from relevant studies identified in PubMed and Scopus databases. Six studies provided contradictory results regarding the effectiveness of resiniferatoxin treatment. The largest study showed no improvement of overall symptoms following a single administration of resiniferatoxin. Three other articles that studied the effectiveness of a single dose of resiniferatoxin gave contradictory results. However, the other two studies, those that examined the effect of multiple or prolonged administration schemes, gave more encouraging results. The use of the regimen is generally well tolerated although mild adverse events such as increase of bladder pain during instillation were sometimes reported by patients and serious adverse events rarely occur. In conclusion, the effectiveness of resiniferatoxin in the treatment of interstitial cystitis remains unknown.     

Pentosanpolysulphate for interstitial cystitis

Interstitial Cystitis (IC) is a chronic disease of unknown etiology which primarily affects women aged 40–60 years. Many plausible theories for the development of IC have been postulated, and one current theory is that these patients have a quantitative and qualitative defect in the glycosaminoglycan (GAG) layer of the urothelium. Such a defect may allow toxic substances in the urine to gain access to the lamina propria and initiate a chronic inflammatory process. Pentosanpolysulphate (PPS) is a sulphated proteoglycan similar in structure to heparin sulphate, which is quantitatively the major GAG on cell surfaces. Exogenously administered PPS has been shown in several studies to decrease bladder pain and urinary frequency and to increase the voided volume. Further studies are required to evaluate the role of PPS in the management of IC patients, with particular emphasis on dosage, route of administration and combination with other compounds.     

Eosinophilic cystitis induced by penicillin

A 30-year-old woman developed classic symptoms of painful bladder disease and eosinophilic cystitis as an adverse effect of penicillin for abdominal actinomycosis. The symptoms were reversible after stopping penicillin.     

Intravesical drug delivery for dysfunctional bladder

The bladder is a hollow organ that can be treated locally by transurethral catheter for intravesical drug instillation or cystoscopy for intravesical drug injection. With advancing technology, local organ‐specific therapy and drug delivery is of expanding interest for treating dysfunctional bladder, including interstitial cystitis/bladder pain syndrome, overactive bladder and sterile hemorrhagic cystitis after chemotherapy or pelvic radiation. Intravesical therapy has shown varying degrees of efficacy and safety in treating interstitial cystitis/bladder pain syndrome, overactive bladder and hemorrhagic cystitis with new modalities being developed. Intravesical (regional) therapy has several advantages than oral (systemic) therapy, including high local concentration and less systemic toxicity. In recent years, intravesical delivery of biotechnological products including neurotoxins and immunosuppressive agents, and delivery platform including liposomes has shown promise for lower urinary tract symptoms. This review considers the current status of intravesical therapy in dysfunctional bladder including interstitial cystitis/bladder pain syndrome, overactive bladder and hemorrhagic cystitis with special attention to lipid based novel drug‐delivery.     

血小板衍化内皮细胞生长因子/胸腺嘧啶磷酸酶和血管内皮生长因子在间质性膀胱炎诊断中的应用

目的 检测血小板衍化内皮细胞生长因子/胸腺嘧啶磷酸酶(PDECGF/TP)和血管内皮生长因子(VEGF)的表达,探讨血管生长因子在间质性膀胱炎(IC)患者膀胱中的表达活性与膀胱镜下的表现及临床症状的关系.方法 选择符合NIH/NIDDK诊断标准的IC患者12例为实验组和12例Ⅲ型前列腺炎患者为对照组.实验组行麻醉下水扩张,膀胱组织活检,常规苏木素-伊红(HE)染色观察肥大细胞数量.应用免疫组织化学检测PDECGF/TP和VEGF表达,进行免疫组织化学阳性细胞计数及免疫组织化学评分(IHS).结果 实验组12名患者在麻醉下水扩张时发现膀胱黏膜点片状出血.常规HE染色病理切片观察可见IC组膀胱组织标本中肥大细胞数目明显高于对照组(P＜0.05),且IC患者的肥大细胞多存在于膀胱组织的黏膜下层,而对照组膀胱组织仅偶见肥大细胞.实验组患者膀胱黏膜PDECGF/TP和VEGF阳性细胞百分比计数、阳性细胞染色强度及HIS评分明显高于对照组(P＜0.05).结论 IC患者血管生长因子PDECGF/TP和VEGF呈高水平表达,通过检测PDECGF/TP和VEGF能够筛选或确诊间质性膀胱炎.

Abstract：

Objective To find out the relationship among the expression of vascular growth factors in patients with interstitial cystitis (IC) and their performance under the cystoscopy as well as the clinical symptoms by detecting the expression of platelet-derived endothelial growth factor/thymine phosphatase (PDECGF/TP) and vascular endothelial growth factor (VEGF). Methods Twelve cases of IC served as the experimental group and 12 cases of type Ⅲ as the control group. The patients in experimental group had bladder mucosa biopsy. The number of mast cells was observed by HE staining. The expression of PDECGF/TP and VEGF and immunohistological score (IHS) were detected by using immunohistochemistry. Results Bladder mucosa hemorrhage points and sheets were observed under water expansion. The number of mast cells existing in the submucosa of the bladder tissue was significantly greater than in control group (P ＜ 0. 05 ). The percentage of PDECGF/TP and VEGF positive cells and IHS in experimental group were significantly higher than in control group (P ＜ 0. 05). Conclusion The expression of PDECGF/TP and VEGF was up-regulated in patients with IC. IC can be screened out or diagnosed by detecting PDECGF/TP and VEGF.     

Short-term results of bilateral S2–S4 sacral neuromodulation for the treatment of refractory interstitial cystitis,painful baldder syndrome,and chronic pelvic pain

We evaluated the efficacy of bilateral caudal epidural sacral neuromodulation for the treatment of refractory chronic pelvic pain (CPP), painful bladder syndrome, and interstitial cystitis (IC). Thirty consecutive patients (21 female, 9 male) with severe refractory symptoms underwent bilateral S2–S4 sacral neuromodulation for CPP/IC. Patients were evaluated with the O’Leary IC symptom and problem index (ICSI, ICPI), the short form of the Urogenital Distress Inventory (UDI-6), and the RAND 36-item health survey (SF-36) preoperatively and 6 months postoperatively. The mean and minimum follow-up were 15 and 6 months, respectively. Of the 30 patients, 23 (77%) had a successful trial stimulation and were permanently implanted. Among these patients, the ICSI and ICPI scores improved by 35 (p = 0.005) and 38% (p = 0.007), respectively. The pain score improved by 40% (p = 0.04) and the UDI-6 score by 26% (p = 0.05). On average, patients reported a 42% improvement in their symptoms. SF-36 scores did not improve significantly. In refractory patients, bilateral caudal epidural sacral neuromodulation is another possible mode of treatment, which appears to improve both pelvic pain and voiding symptoms.     

经尿道电灼与激光治疗重度出血性放射性膀胱炎

目的:探讨出血性放射性膀胱炎的治疗方法。方法:采用经尿道电灼与激光治疗重度出血性放射性膀胱炎12例。结果:所有患者均能迅速控制膀胱出血,疗效满意。复发3例,2例经再次电灼治愈,1例改行右肾皮肤造瘘术。结论:重度患者的治疗关键是尽早彻底清除膀胱内血块与控制活动性出血点,经尿道电灼与激光治疗是控制膀胱内活动性出血的有效方法。     

Sacral neuromodulation for the treatment of refractory interstitial cystitis: outcomes based on technique

Patients with refractory interstitial cystitis (IC) underwent testing with sacral nerve modulation via either a traditional percutaneous approach or a staged procedure. Implanted patients were followed with scaled questionnaires and voiding diaries. Twenty-six patients who had a permanent InterStim placed had a reduction in 24-h voids of 51%. More than two-thirds of patients reported a moderate or marked improvement in urinary frequency, urgency, pelvic pain, pelvic pressure, incontinence and overall quality of life. The test to implant rate of a traditional percutaneous procedure was 52%, compared to a staged procedure of 94%. Assessing sensory response at the time of implant reduced the reoperation rate from 43% to 0%. Ninety-six per cent stated they would undergo an implant again and recommend the therapy to a friend. We concluded that sacral nerve modulation can treat refractory IC symptoms. The response to therapy and the reoperation rate are dependent on the technique used to test and implant the device.Abbreviations IC Interstitial cystitis - TENS Transcutaneous electrical nerve stimulation Editorial Comment: The authors nicely describe a very difficult subset of patients with interstitial cystitis. The patients in this paper have failed six prior treatment modalities before undergoing sacral neural modulation. In this small series the response to therapy and reoperation rate was dependent on the technique used to test and implant the device. Sacral neuromodulation using the staged technique does show significant benefit in the treatment of refractory interstitial cystitis.     

Experimental autoimmune cystitis in the Lewis rat: a potential animal model for interstitial cystitis

To develop an autoimmune animal model for interstitial cystitis (IC), we injected rats with Freund's adjuvant (CFA) containing bladder homogenate (experimentals) or CFA alone (shams). We observed a doubling of urinary frequency in the experimental animals over the shams (P=0.004) and histopathologic changes (venular congestion) consistent with IC. Statistically significant bladder capacity changes were not found. Mast cell (MC) number was not statistically different between experimentals and controls but the number of MCs from section to adjacent section within the same animal's bladder did vary markedly, indicating that MC counts are not a reliable measure of disease in the rat bladder. Splenocytes cultured from the experimental animals and transferred to naive syngeneic recipients were capable of transferring the urinary frequency changes and vascular congestion while splenocytes from animals which did not develop the condition were without effect. In summary, we have developed an autoimmune model for IC consistent with the clinical features of IC. The features of this model can be transferred to naive syngeneic recipients via adoptive splenocyte transfer. The model will permit us to ask and answer important questions about the pathogenesis and treatment of the human disease.