膀胱内灌注电灼联合水扩张法治疗女性间质性膀胱炎

doi:10.19723/j.issn.1671-167X.2023.05.014

摘要/Abstract

摘要：

目的: 探讨肝素/碱化利多卡因(利多卡因与碳酸氢钠混合)协同膀胱内灌注联合水扩张及经尿道电灼治疗女性间质性膀胱炎(interstitial cystitis, IC)的有效性和安全性。方法: 选择2012年1月至2020年12月于中国医科大学附属第一医院泌尿外科就诊，符合美国泌尿外科协会指南的诊断标准，新诊断为IC的女性患者的病例资料进行回顾性分析，诊断时对可疑病变进行膀胱镜检查和活检。所有患者均接受持续12个月的2%(质量分数)利多卡因10 mL + 5%(质量分数)碳酸氢钠5 mL +肝素25 000 IU的膀胱内灌注治疗，根据患者的意愿，选择接受或不接受水扩张及经尿道电灼治疗，将患者分为水扩张和经尿道电灼(hydrodistension and transurethral fulguration, HD/TF)组和非HD/TF组，记录患者治疗前和治疗后1、6、12个月O’Leary-Sant间质性膀胱炎症状指标评分(interstitial cystitis patient symptom index scores, ICSI)、问题指标评分(interstitial cystitis patient problem index scores, ICPI)、耻骨上疼痛视觉模拟评分(visual analog scale, VAS)、功能性膀胱容量(functional bladder capacity，FBC)等。结果: 共收集到患者79例，其中有4例(5.1%)患者因病理诊断为癌或治疗失败而行膀胱切除术被剔除，其余患者均在治疗后1、6、12个月成功随访。重复测量方差分析显示：治疗后ICPI、ICSI和VAS较治疗前均显著降低(P < 0.05)，FBC显著增加(P < 0.05)。治疗后1、6、12个月随访期间FBC持续下降，差异有统计学意义(P < 0.05)；在治疗后1个月和6个月随访时ICSI持续降低，差异有统计学意义(P < 0.05)，而治疗后的6个月与治疗后12个月的ICSI差异无统计学意义(P>0.05)。HD/TF组在治疗后1个月和6个月随访时ICPI持续降低，差异有统计学意义(P < 0.05)，而治疗后6个月与12个月的ICPI差异无统计学意义(P>0.05)。治疗后1、6、12个月其余各项指标之间比较，差异均无统计学意义(P>0.05)。与非HD/TF组相比，HD/TF组的ICPI、ICSI、VAS和FBC改善更早，且VAS和FBC的变化更显著(P < 0.05)。结论: 肝素/碱化利多卡因协同膀胱内灌注加水扩张和经尿道电灼治疗IC是一种有效的治疗选择。膀胱内肝素/碱化利多卡因协同灌注可能成为首选治疗方法，可显著减轻患者和医保系统的经济负担，如果患者能接受，可考虑经尿道电灼联合水扩张的治疗方法。

关键词: 间质性膀胱炎, 膀胱内灌注, 经尿道电灼, 水扩张

Abstract:

Objective: To investigate the efficacy and safety of intravesical instillation of heparin/alkalized lidocaine (lidocaine mixed with sodium bicarbonate) combined with hydrodistension and transurethral fulguration in the treatment of female interstitial cystitis (IC). Methods: Female patients who attended the Department of Urology at the First Hospital of China Medical University between January 2012 and December 2020 and met the diagnostic criteria proposed in the guidelines of the American Urological Association with a new diagnosis of IC were selected for retrospective analysis. Cystoscopy and biopsy of suspicious lesions were performed at the time of diagnosis. All the patients were treated with an intravesical instillation regimen of 2% lidocaine 10 mL + 5% sodium bicarbonate 5 mL + heparin 25 000 IU for a continuous period of 12 months, with or without water dilatation and transurethral electrocautery according to the patient's preference, categorized as hydrodistension and transurethral fulguration (HD/TF) group and non-HD/TF group. The patients were evaluated before and 1, 6, and 12 months after treatment for O'Leary-Sant interstitial cystitis patient symptom index scores (ICSI), interstitial cystitis patient problem index scores (ICPI), visual analog scale (VAS) of suprapubic pain, and functional bladder capacity (FBC) changes. Results: A total of 79 patients were collected in this study. Four (5.1%) of these patients underwent cystectomy due to pathological diagnosis of cancer or treatment failure. The remaining patients were followed up 1, 6 and 12 months after treatment. Repeated-measures ANOVA showed a significant decrease in ICPI, ICSI and VAS and an increase in FBC after treatment compared with before treatment (P < 0.05). FBC continued to decrease during the 1, 6 and 12 months' post-treatment follow-ups, with statistically significant differences; ICSI continued to decrease during the 1 and 6 months post-treatment follow-ups, with statistically significant differences, while the difference between ICSI at 6 months post-treatment and at 12 months' post-treatment was not statistically significant. In the HD/TF group, ICPI continued to decrease in the follow-up from 1 and 6 months after treatment, and the difference was statistically significant, while the difference between ICPI 6 months after treatment and 12 months after treatment was not statistically significant. There was no statistically significant difference between the remaining indicators 1, 6 and 12 months after treatment. ICPI, ICSI, VAS and FBC improved earlier and the changes in VAS and FBC were more significant in the HD/TF group compared with the non-HD/TF group (P < 0.05). Conclusion: Heparin/alkalized lidocaine combination of intravesical instillation with hydrodistension and transurethral fulguration for IC is an effective treatment option. Heparin/alkalized lidocaine combination of intravesical instillation may be the first choice of treatment, which can significantly reduce the economic burden of patients and medical insurance system. If patients can accept it, transurethral fulguration with hydrodistension may be considered.

Key words: Interstitial cystitis, Intravesical instillation, Transurethral fulguration, Hydrodistension

中图分类号:

R694.3

辛鹏,张昊,姜振明. 膀胱内灌注电灼联合水扩张法治疗女性间质性膀胱炎[J]. 北京大学学报（医学版）, 2023, 55(5): 865-870.

Peng XIN,Hao ZHANG,Zhen-ming JIANG. Treatment of intravesical instillation with fulguration-hydrodistention on female interstitial cystitis[J]. Journal of Peking University (Health Sciences), 2023, 55(5): 865-870.

图/表 4

图1

表1

图2

表2

参考文献 29

1	Hanno PM , Erickson D , Moldwin R , et al. Diagnosis and treatment of interstitial cystitis/bladder pain syndrome: AUA guideline amendment[J]. J Urol, 2015, 193 (5): 1545- 1553. doi: 10.1016/j.juro.2015.01.086
2	Engeler DS , Baranowski AP , Dinis-Oliveira P , et al. The 2013 EAU guidelines on chronic pelvic pain: Is management of chronic pelvic pain a habit, a philosophy, or a science? 10 years of development[J]. Eur Urol, 2013, 64 (3): 431- 439. doi: 10.1016/j.eururo.2013.04.035
3	Generali JA , Cada DJ . Amitriptyline: Interstitial cystitis (painful bladder syndrome)[J]. Hosp Pharm, 2014, 49 (9): 809- 810. doi: 10.1310/hpj4909-809
4	Sun Y , Fang Z , Ding Q , et al. Effect of amitriptyline in treatment interstitial cystitis or bladder pain syndrome according to two criteria: Does ESSIC criteria change the response rate[J]. Neurourol Urodyn, 2014, 33 (3): 341- 344. doi: 10.1002/nau.22407
5	Sant GR , Propert KJ , Hanno PM , et al. A pilot clinical trial of oral pentosan polysulfate and oral hydroxyzine in patients with interstitial cystitis[J]. J Urol, 2003, 170 (3): 810- 815. doi: 10.1097/01.ju.0000083020.06212.3d
6	Nickel JC , Herschorn S , Whitmore KE , et al. Pentosan polysulfate sodium for treatment of interstitial cystitis/bladder pain syndrome: Insights from a randomized, double-blind, placebo controlled study[J]. J Urol, 2015, 193 (3): 857- 862. doi: 10.1016/j.juro.2014.09.036
7	Vollstedt A , Tennyson L , Turner K , et al. Evidence for early cyclosporine treatment for hunner lesion interstitial cystitis[J]. Female Pelvic Med Reconstr Surg, 2022, 28 (1): e1- e5. doi: 10.1097/SPV.0000000000001108
8	Ogawa T , Ishizuka O , Ueda T , et al. Pharmacological management of interstitial cystitis /bladder pain syndrome and the role cyclosporine and other immunomodulating drugs play[J]. Expert Rev Clin Pharmacol, 2018, 11 (5): 495- 505. doi: 10.1080/17512433.2018.1457435
9	Crescenze IM , Tucky B , Li J , et al. Efficacy, side effects, and monitoring of oral cyclosporine in interstitial cystitis-bladder pain syndrome[J]. Urology, 2017, 107, 49- 54. doi: 10.1016/j.urology.2017.05.016
10	Malde S , Palmisani S , Al-Kaisy A , et al. Guideline of guidelines: Bladder pain syndrome[J]. BJU Int, 2018, 122 (5): 729- 743. doi: 10.1111/bju.14399
11	Nickel JC , Ehrlich GD , Krol JE , et al. The bacterial microbiota of Hunner lesion interstitial cystitis/bladder pain syndrome[J]. BJU Int, 2022, 129 (1): 104- 112. doi: 10.1111/bju.15519
12	Meng E , Hsu YC , Chuang YC . Advances in intravesical therapy for bladder pain syndrome (BPS)/interstitial cystitis (IC)[J]. Low Urin Tract Symptoms, 2018, 10 (1): 3- 11. doi: 10.1111/luts.12214
13	Lim YN , Dwyer P , Murray C , et al. Long-term outcomes of intravesical dimethyl sulfoxide/heparin/hydrocortisone therapy for interstitial cystitis/bladder pain syndrome[J]. Int Urogynecol J, 2017, 28 (7): 1085- 1089. doi: 10.1007/s00192-016-3232-0
14	Generali JA , Cada DJ . Intravesical heparin: Interstitial cystitis (painful bladder syndrome)[J]. Hosp Pharm, 2013, 48 (10): 822- 824. doi: 10.1310/hpj4810-822
15	Li B, Leng Q, Li C, et al. Comparison of intravesical instillation of hyaluronic acid with intradetrusor botulinum toxin A injection or cystoscopic hydrodistention for ketamine-associated cystitis[J]. J Int Med Res, 2020, 48(11): 300060520973100.
16	Lv YS , Zhou HL , Mao HP , et al. Intravesical hyaluronic acid and alkalinized lidocaine for the treatment of severe painful bladder syndrome/interstitial cystitis[J]. Int Urogynecol J, 2012, 23 (12): 1715- 1720. doi: 10.1007/s00192-012-1802-3
17	Downey A , Hennessy DB , Curry D , et al. Intravesical chondroitin sulphate for interstitial cystitis/painful bladder syndrome[J]. Ulster Med J, 2015, 84 (3): 161- 163.
18	Nickel JC , Jain P , Shore N , et al. Continuous intravesical lidocaine treatment for interstitial cystitis/bladder pain syndrome: Safety and efficacy of a new drug delivery device[J]. Sci Transl Med, 2012, 4 (143): 143ra100.
19	Niimi A , Nomiya A , Yamada Y , et al. Hydrodistension with or without fulguration of hunner lesions for interstitial cystitis: Long-term outcomes and prognostic predictors[J]. Neurourol Urodyn, 2016, 35 (8): 965- 969. doi: 10.1002/nau.22837
20	Ham BK , Kim JH , Oh MM , et al. Effects of combination treatment of intravesical resiniferatoxin instillation and hydrodistention in patients with refractory painful bladder syndrome/interstitial cystitis: A pilot study[J]. Int Neurourol J, 2012, 16 (1): 41- 46. doi: 10.5213/inj.2012.16.1.41
21	Evans RJ , Overholt T , Colaco M , et al. Injection location does not impact botulinum toxin A efficacy in interstitial cystitis/bladder pain syndrome patients[J]. Can J Urol, 2020, 27 (1): 10125- 10129.
22	Rahnamai MS , Marcelissen T , Apostolidis A , et al. The efficacy of botulinum toxin A and sacral neuromodulation in the management of interstitial cystitis (IC)/bladder pain syndrome (BPS), what do we know? ICI-RS 2017 think thank, Bristol[J]. Neurourol Urodyn, 2018, 37 (Suppl 4): S99- S107.
23	Peters KM , Jayabalan N , Bui D , et al. Effect of sacral neuro-modulation on outcome measures and urine chemokines in interstitial cystitis/painful bladder syndrome patients[J]. Low Urin Tract Symptoms, 2015, 7 (2): 77- 83. doi: 10.1111/luts.12054
24	Xu R , Schachar J , Evans RJ , et al. Hydrodistention does not alter bladder gene expression profiles in patients with non-Hunner lesion interstitial cystitis/bladder pain syndrome[J]. Neurourol Urodyn, 2021, 40 (5): 1126- 1132. doi: 10.1002/nau.24680
25	Walker SJ , Plair A , Hemal K , et al. Bladder hydrodistention does not result in a significant change in bladder capacity for interstitial cystitis/bladder pain syndrome patients[J]. Urology, 2019, 132, 81- 86. doi: 10.1016/j.urology.2019.06.031
26	Huang MC , Hsieh CH , Chang WC , et al. Assessment of treatment outcomes of interstitial cystitis with hydrodistention and bladder training by O'Leary-Sant interstitial cystitis symptom and problem indices[J]. Taiwan J Obstet Gynecol, 2018, 57 (5): 718- 721. doi: 10.1016/j.tjog.2018.08.019
27	Yu WR , Jhang JF , Ho HC , et al. Cystoscopic hydrodistention characteristics provide clinical and long-term prognostic features of interstitial cystitis after treatment[J]. Sci Rep, 2021, 11 (1): 455. doi: 10.1038/s41598-020-80252-x
28	Lee SW , Kim WB , Lee KW , et al. Long-term outcomes of ulcerative interstitial cystitis after complete transurethral resection with therapeutic hydrodistention[J]. Int Urol Nephrol, 2021, 53 (2): 219- 227. doi: 10.1007/s11255-020-02637-1
29	Keller J , Chiou HY , Lin HC . Increased risk of bladder cancer following diagnosis with bladder pain syndrome/interstitial cystitis[J]. Neurourol Urodyn, 2013, 32 (1): 58- 62. doi: 10.1002/nau.22283

Metrics

Viewed

Full text

Abstract

Cited

Shared

Discussed

Items	Group	Data	P value
ICPI	Non-HD/TF	13.4±3.0	< 0.01
	HD/TF	15.2±2.1
ICSI	Non-HD/TF	13.5±2.8	0.08
	HD/TF	14.6±2.3
VAS	Non-HD/TF	6.6±1.5	0.14
	HD/TF	7.1±1.4
FBC	Non-HD/TF	112.8±25.3	0.11
	HD/TF	103.1±23.9

Adverse events	Intravesical instillation, n(%)	Hydrodistension with transurethral fulguration, n(%)
Number of patients	75	50
Vomiting	0	1 (2.0)
Fatigue	3 (4.0)	8 (16.0)
Headache	1 (1.3)	0
Dizziness	1 (1.3)	0
Anxiety	2 (2.7)	0
Abdominal pain	3 (4.0)	5 (10.0)
Dysuria	0	0
Urethral pain	25 (33.3)	11 (22.0)
Pyrexia	0	0
Hematuria	13 (17.3)	23 (46.0)

[1]	柯涵炜, 王起, 许克新. 优化环磷酰胺剂量在间质性膀胱炎/膀胱疼痛综合征啮齿动物模型中的应用[J]. 北京大学学报（医学版）, 2024, 56(5): 908-912.
[2]	朱琳,张维宇,许克新. 环磷酰胺诱导SD大鼠膀胱疼痛综合征模型的有效性[J]. 北京大学学报（医学版）, 2022, 54(4): 735-740.
[3]	王佳文,刘敬超,孟令峰,张威,刘晓东,张耀光. 间质性膀胱炎/膀胱疼痛综合征患者生活质量及相关因素分析[J]. 北京大学学报（医学版）, 2021, 53(4): 653-658.