Role of patch cystoplasty in intractable interstitial cystitis/bladder pain syndrome

Abstract

Purpose:

Management of intractable interstitial cystitis/bladder pain syndrome (IC/BPS) is very challenging with no standard treatment. Reconstructive surgery is one of the options. Here, we present our long-term experience of treating intractable IC/BPS with patch/clam ileocystoplasty.

Patients and Methods:

From September 2012, 19 patients diagnosed with IC/BPS underwent patch cystoplasty. Two patients died, so data from 17 patients was analyzed. 15–20 cm segment of the ileum was isolated, leaving distal most 15 cm of ileum from the ileocecal junction intact. The urinary bladder was opened judiciously in the sagittal section, incising anteriorly from the bladder neck to trigone posteriorly. The patch of the ileum was opened at the antimesenteric border and interposed between the two halves of the bladder. Two suprapubic catheters were placed through the bladder segment. No urethral catheter was placed. A global response assessment questionnaire, 10-point pain scale, interstitial cystitis symptom index, and interstitial cystitis problem index were used to evaluate the response to treatment.

Results:

The average age of the patients included was 47 years, 11 females and 6 males. The average follow-up was of 3.9 years, and the median was 3 years. All 17 patients improved, 13 showed marked improvement and 4 moderate improvement. 11 patients had Hunners Lesion, 14 patients are voiding naturally and 3 are on self-catheterization.

Conclusions:

For IC/BPS, surgery should be offered as the last treatment option in cases of intractable disease. In our series, Patch cystoplasty has shown favorable results with satisfactory outcomes and minimum morbidity, and better quality of life even on long-term follow-up.

INTRODUCTION

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic (>6 weeks), debilitating bladder disorder presenting with chronic pelvic or perineal pain with symptoms of discomfort or pressure related to the bladder with urgency and frequency. There is the presence of chronic inflammation, which is not due to infection or identifiable cause. It also impacts the quality of life, sleep, and sexual functions and may cause anxiety and depression.[1] The diagnosis of IC/BPS is clinical so history taking is very important. There are no diagnostic features of IC/BPS and investigations are done to exclude other similar confusable diseases. It is difficult to estimate the exact prevalence of IC/BPS and is believed to be under-diagnosed. In a recent US study using a large sample size, after matching age and gender to the general US population, national prevalence estimates of 0.87% (95% confidence interval [CI]: 0.32, 1.42), with female and male prevalence of 1.08% (95% CI: 0.03, 2.13) and 0.66% (95% CI: 0.44, 0.87), respectively was derived.[2] By this estimate, India has around 12 million patients of IC/BPS.[3] The American Urological Association has recommended certain guidelines for diagnosing and treating IC/BPS. Oral and intravesical therapy, along with patient education and self-care techniques, remains the mainstay for managing IC/BPS. Surgery is indicated if the patients do not respond to routine treatment. The available surgical interventions include supratrigonal cystectomy with augmentation and urinary diversion with or without cystectomy. The majority of intractable cases respond to these surgical procedures. Reconstructive surgery is offered as a last resort as some patients may not improve after major surgery, and surgical complications may decrease patient’s quality of life.

Patch cystoplasty is a preferred surgical intervention for treating neurogenic bladder dysfunction or inflammatory cystitis, as seen in tuberculosis.[4] Limited cases are reported of its application for IC/BPS, along with long-term follow-up. In this article, we share our experience of treating intractable IC/BPS cases with patch ileocystoplasty at our center and review their long-term follow-up.

Definition of intractable interstitial cystitis/bladder pain syndrome

No definition of intractable IC/BPS is available in the literature. We define intractable IC/BPS as the persistence of severe IC/BPS symptoms after adequate treatment with conservative/minimal invasive modalities like oral therapy, intravesical therapy, therapeutic hydrodistension, which may include management of HL if found. The treatment options for intractable IC/BPS are intravesical injection Botox A, neuromodulation (sacral or pudendal), or reconstructive surgery.

PATIENTS AND METHODS

From January 2012 to December 2023, 19 patients of intractable IC/BPS were operated on with patch cystoplasty, out of which we lost two patients, one due to cardiac cause and the other due to malignancy. Records of 17 patients are available for analysis. Before a decision to operate the patients was taken; all 17 patients were adequately investigated and treated with cystoscopy, therapeutic hydrodistension, oral triple therapy, and intravesical therapy. Oral therapy included adequate doses of Amitriptyline, Hydroxyzine, Gabapentin and Pentossan Polysulfate Sodium for a minimum period of 3 months. On failure of oral therapy, patients were treated with intravesical cocktail and/or intravesical Tacrolimus for 6 and 3 doses, respectively. The intravesical cocktail contained a solution of 40 ml bupivacaine, 25,000 units of heparin, and 2 cc dexamethasone. In our experience, 75%–80% of patients in our series improve with these modalities of treatment. Patients who did not improve and were suffering from the severe disease were counseled about various reconstructive surgical options. These patients were also counseled about the possibility of persistent pain after surgery, the need for clean self-intermittent catheterization, and cystectomy in case of failure of surgical procedure. All the patients who consented for patch cystoplasty were subjected to presurgery cystoscopy and multiple cold cup biopsies to rule out any malignancy.

Surgical technique

Surgery was performed under spinal or general anesthesia. Patients were catheterized and positioned in a supine position. A lower midline incision was taken, and the ileocecal junction was identified. It was confirmed that the intended segment of the ileum was reaching the bladder easily without any tension. 15–20 cm segment of the ileum was isolated, keeping the distal-most segment (15 cm) of the distal ileum from the ileocecal junction intact [Figure 1a]. It was confirmed that the blood supply to the isolated segment of the ileum is intact. The continuity of the intestines was restored using a stapler. The ileum was opened on the antimesenteric border using a cautery [Figure 1b]. The bladder was opened in the sagittal section, incision extending 1–2 cm anteriorly from the bladder neck to 1–2 cm away from the trigone posteriorly, taking care of both the ureteric orifices [Figure 1c]. The urethral catheter was removed aseptically, and no part of the bladder was excised. The patch of the ileum was sutured to the opened bladder using 2-0 polyglactin910(vicryl) sutures [Figure 1d]. Two 20 French Foley catheters were placed in the bladder as suprapubic catheters through the bladder segment, and patency was checked. A retropubic drain was placed, and hemostasis was secured. The abdominal incision was closed in layers, and dressing applied. No urethral catheter was placed.

Figure 1.

(a) Keeping 15 cm of terminal ileum from ileo-ceacal junction intact, 15- 20 cm of ileum is isolated. (b)The ileal segment is incised on antimesentric border. (c) Bladder is bivalved sagitally from bladder neck (leaving 1 cm) to posteriorly 1 cm till the trigone. (d) The isolated ileum patch is sutured to the posterior wall of the bladder and the other end is sutured anteriorly using 00 vicryl continuous sutures

Outcome measurements

The primary efficacy outcome measure was the Global Response Assessment (GRA) done in May 2024. The GRA queries “As compared to when you underwent patch cystoplasty, how would you rate your overall pelvic symptoms now?” A 7-point GRA questionnaire was used to evaluate the response to treatment. The responses were recorded on a scale of − 3–3, where −3 was for markedly worse, −2 for moderately worse, −1 for slightly worse, 0 for no change, 1 for slightly improved, 2 for moderately improved, and 3 for a marked improvement. Participants who indicated they were “moderately” or “markedly” improved were considered intervention responders. The GRA was preferred as there is no objective scale to assess response in IC/BPS patients, and GRA score is commonly used in the research related to IC/BPS.

Secondary measures obtained at baseline and in May 2024 included ratings of pain on a 10-point scale and responses to the O’Leary-Sant interstitial cystitis symptom index (ICSI) and interstitial cystitis problem index (ICPI).

The patients were also asked about their sexual life before and after surgery.

Statistical analysis

Data was reported using descriptive statistics, such that continuous variables were reported with mean and standard deviation, and categorical variables were reported utilizing count and percentage.

RESULTS

All patients achieved a marked reduction in pain, frequency, and urgency and were labeled as responders. The average age of the patients included was 47 years (range: 23–64 years), with a greater number of females (n = 11) than males (n = 6). Hunners lesion was present in 11 cases [Table 1]. The average preoperative bladder capacity under anesthesia was 300 cc (100–600cc). The average follow-up was 3.9 years, ranging from 6 months to 11 years. Of the patients operated on for patch cystoplasty, 13 showed marked improvement in long-term (GRA3), and 4 had moderate improvement (GRA2).

Table 1.

Patient data with demographics and follow up details

Sr No	Age	Sex	Date of surgery	Preoperative bladder capacity (cc)	Presence of Hunner’s lesion	Urinevoiding	Present QOL	Follow up duration (years) (till June 2024)	Present status	Interventions required after patch cystoplasty
01	44	Female	September 2012	600	No	CIC	Excellent GRA 3	11	Symptom free	Nil
02	48	Female	February 2014	250	Yes	Yes	Better GRA 2	10	Symptom free for initial 6 years, now has moderate symptoms	Cystoscopy 2019 routine Cystoscopy with HD 2020
03	56	Female	May 2015	UK	No	Yes	Better GRA 2	09	Symptom free, developed incision hernia and CA breast in December 2021	Repair of Hernia in September 2019
04	46	Female	July 2016	200	No	CIC	Excellent GRA 3	07	Symptom free developed incisional hernia postoperative	Repair of hernia in January 2017 Routine cystoscopy done in July 2020
05	55	Male	November 2018	500	No	Yes	Excellent GRA 3	05	Symptom free	Nil
06	52	Female	March 2019	200	Yes	Yes	Excellent GRA 3	05	Symptom free, developed midbrain thrombosis in August 2019	Nil
07	49	Male	May 2019	UK	No	Yes	Excellent GRA 3	05	Voids symptom free but has mild frequency	Nil
08	47	Male	October 2020	150	Yes	Yes	Excellent GRA 3	03	Voids symptom free	Nil
09	47	Female	March 2021	350	Yes	Yes	Excellent GRA 3	03	Voids symptom free	Urethral dilatation done in September 2021
10	61	Female	October 2021	100	Yes	Yes	Excellent GRA 3	02	Voids symptom free	Nil
11	44	Male	May 16, 2022	200	Yes	CIC	Excellent GRA 3	02	CIC	Nil Went in to retention after one year and was catheterised for one month and then on CIC now
12	23	Female	October 10, 2022	550	Yes	Yes	Excellent GRA 3	01	Voids gets flare occasionlly	Nil
13	51	Male	December 23, 2022	250	Yes	Yes	Excellent GRA 3	01	Voids	Dev fecal and urinary fistula from incision which healed conservatively after 4 weeks of catheterisation
14	35	Female	February 24, 2023	600	No	Yes	Excellent GRA 3	01	Voids	Hysterectomy also done at the same sitting
15	44	Male	May 4, 2023	300	Yes	Yes	Excellent GRA 3	01	Voids	Nil
16	47	Female	May 16, 2023	150	Yes	Yes	Better GRA 2	01	Voids	Wound resuturing day 10, GB Rupture in 2nd month. Dev urinary cutaneous fistula. Both cholecystectomy and fistula surgery done laproscopically on 20th of February 2024. Urinary fistula closed but multiple abscesses intraperitoneal present April 2024. Treated with AKT but developed multiple abdominal lymphnodes and right frozen hip in May 2024
17	56	Female	December 20, 2024	250	Yes	Yes	Better GRA 2	00	Voids	Nil

QoL: Quality of Life, CIC: Clean intermittent catheterization, HD: Hydrodistention, GRA: Global response assessment

Patient number 2 [Table 1] developed moderate symptoms 6 years after surgery and was managed with cystoscopy, hydrodistension, and analgesics. Presently (10 years postsurgery), the patient is stable and requires an injectable painkiller once a month, but she is clinically better than before the procedure. Patient number 3 [Table 1] had marked improvement in GRA for 09 years and developed pain and frequency lately, for which the decision to perform cystoscopy is taken.

Patient number 16 [Table 1] had multiple complaints, such as wound resuturing on day 10, gall bladder rupture in 2^nd month and development of a urinary cutaneous fistula. Both cholecystectomy and fistula surgery were done laparoscopically on the same day (February 20, 2024). After the second surgery, multiple intraperitoneal abscesses developed in April 2024. She was treated with anti-tuberculosis therapy but now she has enlarged? abdominal lymph nodes and signs of frozen hip for which she is being investigated. She has urinary leak and minimal bladder pain. Patient number 17 [Table 1] was operated in December 2023 but has frequency and urgency every hour but comparartively its better than her pre-operative frequency of every 5 min. She has no pain.

Table 2 contains data about pre-operative and postoperative ICSI, ICPI, pain score and sexual activity. It is worth noting that before surgery all the patients had very severe disease presentation with maximum 19 ICSI score, maximum 16 ICPI score and a maximum of 10 on a 10-point pain scale.

Table 2.

Patient data with interstitial cystitis symptom index, interstitial cystitis problem index, 10 point pain scale and sexual activity details

Patient number	Preoperative ICSI score	Postoperative ICSI score	Preoperative ICPI score	Postoperative ICPI score	Preoperative pain score	Postoperative pain score	Preoperative sexually active	Postoperative sexually active	GRA
1	19	3	16	5	10	1	No	Yes	3
2	19	10	16	2	10	7	No	No	2
3	19	13	16	10	10	2	No	No	2
4	19	8	16	0	10	0	No	Yes	3
5	19	0	16	0	10	0	No	Yes	3
6	19	0	16	0	10	0	No	No	3
7	19	2	16	0	10	0	Yes	Yes	3
8	19	2	16	0	10	0	No	Yes	3
9	19	0	16	0	10	0	No	Yes	3
10	19	2	16	0	10	0	Yes	Yes	3
11	19	3	16	0	10	0	Yes	Yes	3
12	19	7	16	0	10	1	No	Yes	3
13	19	1	16	0	10	0	Yes	Yes	3
14	19	8	16	0	10	0	No	No	3
15	19	7	16	3	10	0	Yes	Yes	3
16	19	6	16	2	10	3	No	No	2
17	19	15	16	0	10	0	No	No	2
Mean	19	5	16	2	10	1

The patient numbers are listed according to the serial numbers shown in Table 1. ICSI: Interstitial cystitis symptom index, ICPI: Interstitial cystitis problem index, GRA: Global response assessment

The mean ICSI score was 19 before surgery and came down to 5 after surgery. The mean ICPI before surgery was 16, which was reduced to 2 postsurgery. The mean pain score pre and postsurgery was 10 and 1, respectively.

6 female patients were sexually not active before and after surgery due to pain, cultural, religious and social reason. 5 patients were sexually active before surgery and continue to be active after surgery. 6 patients were sexually not active before surgery due to pain but are active after surgery as there is absence of pain now.

Complications after the procedure are discussed in Table 3 and included the development of an incisional hernia in three patients (17.64%) for which hernioplasty was performed. Three patients failed to void urine by themselves, and clean intermittent catheterization was required (17.64%). One patient developed vesico-ileal-cutaneous fistula (5.88%), which healed in 4 weeks after urethral catheterization and was symptom free 6 weeks postsurgery. One more patient developed vesicocutaneous fistula (5.88%), which did not heal over a period of 9 months and was repaired laparoscopically and now there is minimum leak. Overall quality of life improved in all patients, and all were willing to recommend this surgery to other patients with intractable disease.

Table 3.

Complications after procedure, treatment provided and response to treatment

Complication	Number of patients	Treatment offered	Response
Incisional hernia	3	Hernioplasty
Failure in voiding urine freely	3	Intermittent catheterization
Vesico-ileal cutaneous fistula	1	Urethral catheterization	Healed in 4 weeks
Vesico-cutaneous fistula	1	Laparoscopic repair	Minimal leak

DISCUSSION

Patch cystoplasty/clam cystoplasty has been recommended to treat reduced capacity or poor compliance of the bladder commonly found in neurogenic bladder, tuberculosis, schistosomiasis, postradiation therapy, and chemotherapy.[5,6] The role of patch cystoplasty in IC/BPS has shown variable results in limited studies.[7,8,9] These studies have shown satisfactory results in cases of IC/BPS with Hunner’s lesion and small capacity bladder, but recurrence of symptoms is also reported.

The diagnosis of IC/BPS is clinical and investigations are required to rule out other confusable diseases. There is no pathognomonic test to diagnose IC/BPS, but cystoscopy with hydrodistension and bladder biopsy can help to reach to a conclusion. Cystoscopy findings of glomerulations and Hunner’s lesion support the diagnosis of IC/BPS. A histological finding of bladder biopsy shows infiltration of inflammatory cells, granulation tissue, and mastocytosis of the detrusor with or without fibrosis.[10,11] But a diagnosis of IC/BPS is made after excluding other urogenital pathologies showing similar symptoms. We have earlier reported normal bladder mucosal findings in 21% patients of IC/BPS in a large series of 181 cystoscopies done at our center.[3]

The exact etiology of IC/BPS is unknown, but it is believed to be multifactorial: urothelial and GAG defect, bladder permeability barrier breakage with increased permeability, mast cell infiltration, infection, autoimmunity activation, and central sensitization are various hypothesis.[12,13]

Surgical intervention is kept as the last modality in cases continuing with severe pain despite adequate conventional treatments. Supratrigonal cystectomy with cystoplasty and urinary diversion with or without cystectomy are the available surgical options commonly performed. In a systemic review by Osman et al., a total of 448 patients underwent surgery: subtotal cystectomy with cystoplasty (48.6%), cystectomy and orthotopic neobladder (21.9%), cystectomy and ileal conduit (11.2%), and urinary diversion only (18.3%). Symptomatic improvement occurred in 77.2%, with higher rates in the total cystectomy and orthotopic neobladder group. Thirty-one patients (6.9%) required secondary total cystectomy and/or ileal conduit diversion; 48.4% subsequently improved. Seventeen studies reported 102 complications overall (26.5%), and overall mortality was 1.3%.[9] Patients with end-stage bladder disease, bladder centric disease, small capacity bladder and with HL have shown better results than patients with normal capacity bladder and without HL.

In a recent long-term review of supratrigonal cystectomy and augmentation in 26 cases, two patients required early diversion in 1^st post-operative year. 14/26 patients voided naturally and others needed either CIC or suprapubic catheter for drainage. Five patients (19.2%) had recurrent pain and urgency after 3–9 years requiring injection botox in 2 patients and neuromodulation in 3. 15 patients had marked improvement and 7 had moderate improvement. Patient satisfaction was high in this series with low diversion rate.[14] In another study by Kim et al. on 45 patients, augmentation ileocystoplasty with supratrigonal cystectomy, showed significant improvement in ICSI (17.8 vs. 9.9, P < 0.001) and ICPI (14.4 vs. 6.5, P < 0.001) compared to baseline readings.[15] Though supratrigonal cystectomy has good functional results, it is associated with postprocedure complications such as infection, pneumonia, thromboembolism, intestinal obstruction, malabsorption and urinary retention.[15] Repeat surgery was required in 2 patients for postoperative hemorrhage and incisional hernia and 2 patients required transurethral resection for remnant ulcer.

There is very little mention of patch cystoplasty in the medical literature as a treatment of choice for intractable IC/BPS and very few cases have been reported. We have performed patch cystoplasty in intractable IC/BPS with very good results. In patch cystoplasty, a segment of the bowel, commonly the ileum, is attached to the bladder. Mostly indicated for bladder with small capacity, the application of patch cystoplasty for normal capacity bladder is not mentioned in literature. In the present series, patch cystoplasty was performed in 17 cases of IC/BPS, with 9 patients having more than 200 cc capacity bladder (range 250–600 cc). The surgical outcomes were favourable, with no mortality due to patch cystoplasty. There is the recurrence of symptoms in only two patients in long run but even then these patients are much better than what they were before. This presentation is unique as it explores newer insight in the field of urology for treating intractable IC/BPS, different from the routine indications. Presurgical multiple biopsy is done to rule out urothelial malignancy. During surgery, no urethral catheter is put to reduce urethral/perineal pain in post-operative period. Instead two suprapubic catheters are kept. This modification decreases morbidity in immediate post-operative period. Complications of patch cystoplasty include incomplete voiding requiring self-catheterization, metabolic acidosis, mucus and stone formation, infection, malignancy in the intestinal segment or rupture of the bladder, and persistence of pain.[16,17] In this series, patients did respond well with very few complications, which were managed either conservatively or surgically and all patients had improvement in quality of life. No patient needed revision surgery or cystectomy for persistent pain. Our long-term data, ranging from 1 year to 12 years, has shown favorable outcomes.

There is tremendous improvement in the quality of life of all these patients, including sexual function. None of the patients had deterioration in sexual function. Dyspareunia and painful ejaculation improved. There was no disease flare post intercourse in sexually active patients after patch cystoplasty. The sexual life of patients improved. Patients who failed to perform sexual intercourse for years before surgery for fear of pain could indulge in regular sex post-surgery.

As no major dissection is involved in patch cystoplasty the sexual function is not affected. There is no disfigurement as most of the patients void by themselves naturally. There is no mention about the effect of reconstructive surgery on sexual function in the present literature in IC/BPS patients. A smaller sample size of 17 patients is a limitation of our study, restricting generalization of study findings. This also gives scope for a study with larger cohort in order to comfirm the findings and validate it as an suitable alternative for treating IC/BPS in the future.

The concept that leaving a diseased bladder inside will cause pain after cystoplasty is not correct, as proved in this series. Even in neurogenic bladder, tuberculous bladder, and OAB, patch cystoplasty gives good results in spite of diseased bladder being left inside.

Advantages of patch cystoplasty

• There is minimum morbidity in comparison to other available surgical options. Post-operative recovery is very fast

• No complication of uretero-enteric anastomosis like ureteric stricture or vesico-ureteric reflux leading to pyelonephritis as the natural ureteral meatus in bladder is not disturbed

• Very small segment of ileum is used, so there is no chance of metabolic disturbances after surgery even in long term. Patients do not require any medication for acidosis in patch cystoplasty even in long run

• The bladder sensations are present as no part of bladder is resected and most of the patients void with minimal residue

• As no major dissection is done, no nerves or vessels are dissected and therefore no effect on sexual function post-surgery, especially in males

• Post-surgical complications are few and can be managed easily.

Why does patch cystoplasty work in intractable IC/BPS:

• In the normal bladder, the urothelium unfolds as the bladder distends and expands due to exocytosis of the apical membrane[18]

• This increases the surface area of contact between urothelium and potential urotoxins and further explains why bladder pain in patients with IC/BPS is relieved by bladder emptying

• Following patch cystoplasty, however, the surface area of urothelium is reduced (not unfolded) because now a proportion of the bladder consists of ileum, which unfolds and distends more easily owing to greater compliance of the bowel versus chronically inflamed bladder. This decreases the surface area of contact between urothelium and the potential urotoxins

• The normal frequency/volume relationship of afferent nerve firing may be modulated by the stretch-dependent release of mediators from the urothelium e.g. acetylcholine, adenosine triphosphate, nerve growth factor[17]

• Many of these mediators are increased in patients with IC/BPS, which may lower the threshold for initiation of afferent nerve firing or increase the rate of afferent nerve firing in response to bladder filling

• The stretching factor of Detrusor is effective when the bladder muscles acts as unit

• This detrusor unit is interrupted by a patch of ileum sutured in between bi-valved urinary bladder

• Following augmentation ileocystoplasty, there is less tension in the bladder wall at a given bladder volume because a proportion of the bladder consists of more compliant ileum increasing the threshold for afferent nerve firing which improves the symptoms. This proportion of ileum increases as bladder capacity slowly increases post-surgery.

Summarising we believe that patch cystoplasty corrects the abnormality of detrusor stretch resulting in decreased tension in bladder at a given bladder volume, and this modifies firing from stretch receptors decreasing urgency and pain.

CONCLUSIONS

IC/BPS is considered a debilitating chronic disease as it is difficult to diagnose and treat. We have proved that patch cystoplasty is a good surgical option for patients with intractable IC/BPS. It is effective in not only small-capacity and Hunners lesion IC/BPS bladder but also in normal capacity and non-Hunners lesion disease. The morbidity, complications, and re-surgery rate is very less in patch cystoplasty in comparison with other available reconstructive surgical options for intractable disease. The role of patch cystoplasty for IC/BPS has been reinvented by us. Even long-term follow-up data have shown satisfactory outcomes with minimal complications.

Although the series is small, its message is very loud and clear, and there is a need to recommend patch cystoplasty in intractable cases of IC/BPS.

Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.