Cure of Interstitial Cystitis and Non-Ulcerating Hunner’s Ulcer by Cardinal/Uterosacral Ligament Repair

Interstitial cystitis (IC)/painful bladder syndrome in all its manifestations, from definitions to diagnosis to management remains an enigma. In 2009, Hanno and Dmochowski [1] summarized the state of knowledge as follows: “Standardization of nomenclature, definition, and evaluation of interstitial cystitis/bladder pain syndrome/painful bladder syndrome was and remains a problem. Hunner’s ulcer is not necessarily an essential part of the diagnosis.”

The current definition for interstitial cystitis/bladder pain syndrome [2] is “persistent or recurrent chronic pelvic pain, pressure, or discomfort perceived to be related to the urinary bladder accompanied by at least one other urinary symptom such as an urgent need to void or urinary frequency diagnosed in the absence of any identifiable pathology which could explain these symptoms.”

Hunner’s lesion, previously a hallmark of IC, is no longer considered essential for diagnosis. In fact, the very concept of IC is in doubt. In 2018, Meijink [3], president of the Interstitial Cystitis society ESSIC stated “With all patients being bundled together as one ‘syndrome,’ with no subtyping, study data have been unreliable and even meaningless. This is further exacerbated by the fact that there is still no international consensus on nomenclature, terminology, and definitions nor on diagnostic criteria. This is damaging for research, data sharing, and comparing and ultimately for the patient and treatment since the evidence from drug studies is erratic and inconsistent.” Unsurprisingly, there is no single accepted treatment. The American Urological Association lists 6 “levels of treatment” each containing several totally different options.

Frau C., a 73-year-old lady presented in March 2016 with urgency, half-hourly frequency and nocturia twice/night. There was no wetting, and urinalysis was normal. She was assessed by the validated Integral Theory System Questionnaire [4] and diagnostic algorithm (Fig. 1), which uses symptoms to locate ligament damage. On examination, a moderate cystocele and an entero/rectocele were seen with laxity of the cardinal/uterosacral ligaments (USLs) and pubocervical/rectovaginal fascia. “Simulated operation,” mechanical support of the anterior vaginal wall/apex with a speculum (Fig. 2), led to almost complete urgency and pain resolution as per Wu et al. [5]. Urodynamic examination showed a maximum capacity of 430 mL (limited by pain), detrusor stability, normal compliance, and no leakage. On cystoscopy under general anaesthesia, bladder capacity was 300 mL showing diffuse distension bleeding, chronic cystitis with patchy mucosal reddening, glomerulations, and a non-ulcerating Hunner’s ulcer. Resection biopsies showed large numbers of mast cells within the muscular layer. Further clinical testing with a 2nd “simulated operation,” a tampon inserted into the vaginal apex to support the USLs considerably improved both urge and pain. In June 2016, an apical repair with a tissue fixation system (TFS) tensioned tape was performed.

Post-operatively, there was good anatomical correction of the apical descensus. The patient reported that her symptoms were gradually disappearing with voiding reduced to 5–6 times daily and nocturia once.

A follow-up cystoscopy in September 2016 showed complete healing of the Hunner’s ulcer, no bleeding, and no glomerulations. The bladder capacity was 700 mL. Since then, the patient has been seen regularly twice yearly and is free of any symptoms suggestive of IC.

Frau C. was treated according to the integral theory paradigm (ITP) [6], specifically, the “posterior fornix syndrome (PFS)”: grouped symptoms of urge, frequency, nocturia, chronic pelvic pain, and abnormal emptying caused by uterosacral ligament laxity (Fig. 1). Inserting the lower blade of a bivalve speculum confirmed lax USLs were causing the pain and urge [5] (Fig. 2). The speculum stretches the vagina to mechanically support USLs. Instantaneous disappearance of urge and pain symptoms supports the concept of cure by restoring the integrity of muscle/ligament complex (http://www.cms.galenos.com.tr›Uploads›Pelviperineology-32-55-En" xmlns:xlink="http://www.w3.org/1999/xlink"www.cms.galenos.com.tr›Uploads›Pelviperineology-32-55-En).

Non-surgically, a >50% improvement in pain, urge, frequency, and nocturia has been reported using squatting-based exercises which strengthen the 3 directional forces and ligaments they contract against [7]. Surgically, experience with younger women with chronic pelvic pain of unknown origin and presumably good USL collagen has shown good cure rates for PFS symptoms (rectangle, Fig. 1) with native tissue USL plication [6]. For post-menopausal women, poor results probably because of collagen deficiency in ligaments necessitated application of a posterior sling to reinforce USLs, achieving high cure rates for chronic pelvic pain, urge, nocturia [8‒11], and classic symptoms of IC [2]. Long-term cure at 60 months in a group of 70-year-old women using a TFS CL/USL sling [11] has been reported for prolapse, pelvic pain, and urge.

Our findings with Frau C. support the hypothesis of Wyendale that bladder pain may arise from bladder unmyelinated C-fibres. This may be due to an inability of the 3 reflex muscle forces (arrows, Fig. 2) to tension the bladder base sufficiently to support the stretch/pain receptors “N” because of looseness in the suspensory ligaments (USL, Fig. 1) they contract against. This may cause the now unsupported stretch receptors “N” to fire off excess afferent urge/pain impulses, perceived by the cortex as urge and bladder pain. Alternatively, it is known that chronic pelvic pain may be due to inability of loose USLs to support the T11-L2 and S2-4 visceral nerve plexuses located 2–3 cm before their attachment to cervix [12].

The glomerulations may have been caused during bladder filling by the weight of the bladder contents creating a downward rotation of the bladder into the vagina, to cause mechanical obstruction of low pressure vesical veins. Glomerulations were not present post-operatively. We attribute this to the TFS cardinal ligament sling curing the cystocele, as predicted, (Fig. 1). We hypothesize that repeated mucosal venous outflow obstruction over time may have caused sufficient hypoxia to induce inflammatory mast cell infiltration. Alternatively, unsupported visceral nerve fibres supplying the bladder may have sent afferent signals to the cortex "tricking it" to believe the impulses came from the end organ itself. The cortex sends inflammatory mast and other cells to the endorgan (in this instance bladder).

Statements from the Interstitial Cystitis Society itself indicate a chaotic situation in the very concept of IC: definitions, symptomatology, treatment, unknown pathogenesis, and no known cure. Frau C. was treated according to a different paradigm, the Integral Theory paradigm, ITP, as a typical case of posterior fornix syndrome, PFS, which was successful. All the descriptions of IC in the literature to date indicate equivalence to PFS, at least in women. If so, then patients with symptoms of IC who have a positive speculum test may, at least theoretically, be potentially curable by USL repair, ligament plication for the young, and sling for the old. These questions need to be explored.

The study was conducted according to the WMA Declaration of Helsinki. Written informed consent was obtained from the patient, and ethical approval was obtained for publication of this case report.

None for any author.

None declared.

All authors contributed to conceptualization and writing. Surgery: K.S.; figures: P.P.