British Journalof Urology (1991), 6 8 , 4 8 3 4 8 6 01991 British Journalof Urology

Subtrigonal Phenol Injection. How Safe and Effective is it? C. H. CHAPPLE, S. J. HAMPSON, R. T.TURNER-WARWICK and P. H. L. WORTH Department of Urology, Middlesex Hospital, London

Summary-A series of 24 patients underwent 27 transtrigonal phenol injections for the treatment of bladder instability. Only 2 of 18 patients with detrusor instability and 2 of 6 with detrusor hyperreflexia continued to derive benefit from the procedure 6 months after it was carried out. Serious complications attributable to phenol were seen in 2 patients in this series and in a further 4 patients referred for complications resulting from this therapy in other centres. These results and a review of the literature lead u s to suggest that transvesical phenol injection should not be used except in the hyper-reflexic bladder when no alternative treatment is possible. Particular care should be exercised in patients who have undergone extensive prior surgery or radiotherapy. The symptoms of bladder overactivity resulting from detrusor instability or hyper-reflexia are distressing for the patient and their satisfactory management is often problematic for the clinician. Bladder training supplemented where necessary by the use of anticholinergic agents and the occasional use of DDAVP form the mainstay of treatment (Frewen, 1978; Moisey et al., 1980). Once these measures have failed it has been suggested that prior to embarking on major surgery, transtrigonal phenol injection therapy may be useful (Ewing et al., 1982). Although initial series (Ewing et al., 1982; Blackford et al., 1984; Cameron-Strange and Millard, 1988) reported favourable results, later reports have suggested it to be more limited both in terms of success and duration of action (Nordling et al., 1986; Wall and Stanton, 1989; Rosenbaum et al., 1990). We report our experience with this technique in 24 patients and review the complications resulting from this therapy in a further 4 patients referred to our unit. Both of these aspects are discussed in the context of the current world literature.

Patients and Methods

A total of 24 patients underwent 27 transvesical subtrigonal phenol injections for symptoms of Accepted for publication 22 November 1990

bladder instability. The group comprised 18 patients (15 women) of mean age 52.3 k 4 .3 years with detrusor instability (DI) and 6 patients (5 women) of mean age 50.8 7.2 years with detrusor hyperreflexia (DHR). The DI group were idiopathic in aetiology. The DHR group included 2 patients with multiple sclerosis (MS), 2 post cerebrovascular accidents (CVA) and 1 each motor neurone disease (MND) and dementia. The mean follow-up after phenol injection was 14.7k2.7 months for D I patients and 11.7 ? 4.0 months for the D H R group. All patients underwent videocystometrography and all had been treated with conventional therapy, including bladder retraining and pharmacotherapy . Transtrigonal injection of a 6% aqueous solution of phenol was carried out under general anaesthesia following the guidelines laid down by Ewing et al. (1982). Patients were allowed home the following day and were reviewed in out-patient clinics for the first 6 months and thereafter as necessary. Results Detrusor Instability Group. Ten of the 18 women reported an improvement at 1 month. This figure fell to 7/18 at 3 months and 2/18 at 6 months. Three patients had 2 injections of phenol; 2 of them derived no benefit at all from either injection and 1 had only a transient response (4months). Two

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484 patients had urodynamic studies which reverted to stability after the injections but failed to show any subjective improvement at 3 months. Detrusor Hyper-rejexia Group. Improvement was seen in 4 of the 6 patients at 3 months. Two (1 MS, 1 CVA) became wet again by the 6-month review but 2 patients (1 MND, 1 MS) with indwelling catheters have ceased leaking around their catheters and this improvement was maintained at the 12month review. A 69-year-old with dementia failed to show any improvement and a 32-year-old with a previous CVA developed a vesicovaginal fistula 2 months after injection. This was repaired via an abdominoperineal approach and she subsequently underwent an enterocystoplasty with good result. Complications. There were 2 significant complications in this series (cases 1 and 2), with a further 4 patients who had been treated at other centres being referred for the further management of complications (cases 3 to 6).

Case Reports Case 1. A 63-year-old female with severe detrusor instability was improved after phenol injection therapy for 4 months. A second injection was followed 6 weeks later by a vesico-ureterovaginal fistula. She underwent a successful repair of this, which was associated with a marked vaginal fistula. This was repaired successfully but was associated with marked tissue fibrosis related to her phenol injection therapy. She was troubled by persistent urinary incontinence and on examination was found to have a rigid patulous urethra associated with marked periurethral fibrosis. A reduction sphincteroplasty restored full urinary continence.

Case 2. A 32-year-oldfemale with detrusor hyper-reflexia underwent transtrigonal phenol injection therapy. She was not improved and 2 months later developed a vesicovaginal fistula. This was repaired using a combined abdominoperineal approach; at surgery dense fibrosis was evident in the perivesical tissues at the base of the bladder. A clam enterocystoplasty was then successfully carried out. Case 3. A 70-year-old female was referred with recalcitrant detrusor instability and continuous urinary incontinence. She had previously undergone 2 vaginal and 2 abdominal surgical repairs which had proved unsuccessful and had then been treated with transtrigonal phenol therapy; 4 weeks after this she had become continuously incontinent of urine. On examination she was found to have a rigid “pipe-stem’’urethra. At surgical exploration the base of the bladder and periurethral area were encased in dense fibrous tissue. A reconstructive procedure was not possible and urinary diversion was carried out.

BRITISH JOURNAL OF UROLOGY

Case 4. A 20-year-old female was referred with complications resulting from transtrigonal injection therapy. She had been treated with 2 injections spaced 8 months apart. An increase in functional bladder capacity resulted and her symptoms were improved. Eight months later she presented with bilateral loin pain and recurrent urinary incontinence and on investigation was found to have right vesicoureteric reflux, left ureteric stenosis and stress incontinence; these abnormalities were felt to be a result of her phenol injection therapy. At subsequent surgery, when bilateral ureteric reimplantation was carried out, she was found to have dense fibrosis at the base of the bladder and around the bladder neck and urethra. Following an additional bladder neck repositioning procedure and clam cystoplasty she was rendered symptom-free. Case 5. A 71-year-old female was referred with urinary retention following transtrigonal phenol injection therapy. Pre-operative urodynamic assessment had demonstrated detrusor instability and repeated investigations post-operatively have shown detrusor hypocontractility. She is now on long-term intermittent self-catheterisation. Case 6. A 48-year-old female with detrusor instability was referred with a vesicovaginal fistula which developed 4 weeks after phenol injection therapy. She had been treated with radiotherapy for carcinoma of the cervix several years previously. The fistula was successfully repaired via an abdominoperineal route and she remains free of detrusor instability 22 months later.

Discussion Phenol is a potent neurolytic agent which in concentrations greater than 5% produces a nonreversible denaturing of protein (Nathan et al., 1965) and when administered experimentally (in rats) directly to the paravesical plexus results in denervation of the detrusor muscle (Parkhouse et al., 1987). The rationale behind the use of transtrigonal phenol injections is that the consequent damage to nerves in the paravesical pelvic plexus should result in a relative detrusor hypocontractility and hence the abolition of unwanted detrusor contractions. A review of the literature on the use of transtrigonal phenol injections over the last 10years reveals documentation of 318 patients undergoing 370 procedures. The largest groups were patients with DI and DHR; 56 of 153 DI patients (37.5%) were considered to have derived benefit and maintained improvement 3 months after treatment. The DHR group achieved a better success rate, with 61 of 107 patients (63.7%) improved at 3 months. The patients in the other 2 treatment categories (hyper-

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SUBTRIGONAL PHENOL INJECTION

Table 1 Published Series of Transvesical Phenol Injection Author

Year

Patients/ injections

Ewing e f al. Ewing et al. Blackford et al. Nordling Cameron-Strange and Millard Wall and Stanton Rosenbaum et al. Present study

1982* 1983 1984 1986

30 24 116 16/19

1988 1988 1990 1990

40 28/40 60194 24/27

Detrusor instability

Detrusor hyper-rejlexia

Post-operative hypersensitivity

Figures in brackets are the numbers of patients considered to be improved at 3 months. * This series has not been used in the cumulative response. The 20 MS patients in Ewing’s 1982 series are assumed to be included in the 1983 series. t This is the number improved at 6 months (all others are 3 months).

sensitive and post-operative) are tabulated in Table 1. Our results parallel those of the most recent studies (Nordling et al., 1986; Wall and Stanton, 1989; Rosenbaum et al., 1990) in suggesting that the benefit of transvesical phenol injection is shortlived, with only 2 of 18 patients with detrusor instability having any improvement at 6 months. Our hyper-reflexic group is small but does seem to include the occasional long-lived successful treatment. A possible indication for this therapy may be found in the subgroup of patients with long-term catheters where bypassing is a problem, as demonstrated by one of our patients and emphasised by the report of Murray et al. (1986), where 7/83 patients in this category remained improved at 1 year later. The overall complication rate against which this degree of success must be balanced is 11% (Table 2) Table 2 Documented Complications in 318 Patients Undergoing 370 Extravesical Phenol Injections Complications

No. (%I

Chronic retention of urine Acute retention of urine Fistula formation Significant haematuria Sciatic nerve palsy (transient) Trigonal ulceration Ureteric reflux (transient) Ureteric reflux (permanent) Ureteric stenosis Periurethral fibrosis Vesical calculus

11 (3) 10 (2.7) 6 (1.4) 5 (1.3) 2 2

Total

42 (1 1.3)

(some of these have already been detailed above in the case reports). The complications which ensue are the consequence of tissue damage resulting in marked tissue fibrosis around the base of the bladder and associated structures including the bladder neck, urethra and ureters. Three patients developed rigid urethras as a consequence of periurethral fibrosis; only one of these patients had undergone previous surgery to the bladder neck and in this case functional reconstruction of the urethra was not possible. Transient ureteric reflux has been described previously (Ewing et al., 1982) but not permanent reflux or ureteric stenosis, both of which occurred in one of our patients. In more extreme cases tissue damage may result in tissue necrosis (fistulae) and other workers have also reported the development of fistulae (Nordling et al., 1986; Cameron-Strange and Millard, 1988; Wall and Stanton, 1989). Predisposing factors include tissue ischaemia and scarring resulting from previous surgery or radiotherapy and second doses of sclerosant. This was clearly demonstrated in a study where ethanol was used instead of phenol but where fistulae developed in 3/10 patients-in 2 following prior radiotherapy and in 1 following injection of 230ml of sclerosant (Harris et al., 1988). Although neural damage is the aim of this therapy, the difficulty of accurately titrating and confining the delivery of phenol to the area of the paravesical plexus has been demonstrated by Rosenbaum et al. (1990). Urinary retention is a recognised complication of the procedure and is almost desirable if unstable contractions are abolished (Ewing et al., 1982) and symptoms relieved, but becomes in itself clinically significant if it

486 results in the patient being unable to produce a voluntary contraction (Cox and Worth, 1986), as in case 5. Local spread of phenol away from the perivesical area may result in severe associated neural damage, including partial sciatic nerve palsy (Blackford et al., 1984) and impotence (McInerney, 1991). In addition, the systemic absorption of phenol is not without danger ;multifocal ventricular ectopia has been reported after transtrigonal injection (Forrest and Ramage, 1987). Finally, there is the unusual complication of eye injuries occurring in medical staff from phenol splashing (CameronStrange and Millard, 1988). Our experience confirms the growing weight of evidence in the literature to suggest that transtrigonal phenol injection has little part to play in the management of the unstable bladder. This report emphasises the small yet significant incidence of severe side effects which accompany this therapy, particularly in patients who have undergone previous surgery or radiotherapy. We would therefore suggest that this therapy should be dropped from routine use, although it may still be of use for the patient with refractory hyper-reflexia and in highly selected cases of detrusor hypersensitivity where all else has failed. The use of repeated injections should be avoided because of the increased risk of complications.

References Blackford, H. N., Murray, K., Stephenson, T. P. er al. (1984). Results of transvesical infiltration of the pelvic plexuses with phenol in 116 patients. Br. J . Urol., 56,647-649. Cameron-Strange,A. and Millard, R. J. (1988). Management of refractory detrusor instability by transvesical phenol injection. Br. J . Urol., 62, 323-325. Cox, R. and Worth, P. H. (1986). Chronic retention after extratrigonal phenol injection for bladder instability. Br. J . Urol., 58,237-238.

BRITISH JOURNAL OF UROLOGY Ewing, R., Bultitude, M. I. and Shuttleworth, K. E. (1982). Subtrigonal phenol injection for urge incontinence secondary to detrusor instability in females. Br. J . Urol., 54,689-692. Ewing, R., Bultitude, M. I. and Shuttleworth, K. E. (1983). Subtrigonal phenol injection therapy for patients with multiple sclerosis. Lancet, 1, 1304-1305. Forrest, T. and Ramage, D. T. (1987). Cardiac dysrhythmia after subtrigonal phenol. Anaesfhesia, 42, 777-778. Frewen, W. K. (1978). An objective assessment of the unstable bladder of psychosomatic origin. Br. J . Urol., 46,246-249. Harris, R. G., Constantinou, C. E. and Stamey, T. A. (1988). Extravesical subtrigonal injection of 50% ethanol for detrusor instability. J . Urol., 140, 111-1 16. McInerney, P. D., Vanner, T. F., Matenhelia, S. et d (1991). Assessment of the long-term results of subtrigonal phenolisation. Er. J . Urol.,67, 586587. Moisey, C. U., Stephenson, T. P. and Brendler, C. B. (1980). The urodynamic and subjective results of treatment of detrusor instability with oxybutinin hydrochloride. Br. J . Urol., 52, 472-475. Murray, K., Mundy, A. R., Blackford, H. N. et al. (1986). Transvesical phenolisation of the pelvic plexuses : a simple technique for the treatment of refractory detrusor instability and hyperreflexia. Urol. Int., 41, 202-206. Nathan, P. W., Sears, T. A. and Smith, M. C. (1965). Effects of phenol on the nerve roots of the cat: an electrophysiological and histological study. J . Neurosci., 2,7-29. Nordling, J., Steven, K., Meyhoff, H. H. e t d (1986). Subtrigonal phenol injection: lack of effect in the treatment of detrusor instability. Neurol. Urodynam.,5,449-451. Parkhouse, H. F., Gilpin, S. Gosling, J. A. et al. (1987). Quantitative study of phenol as a neurolytic agent in the urinary bladder. Br. J . Urol.,60,410412, Rosenhaum, T. P., Shaw, P. J. and Worth, P. H. (1990). Transtrigonal phenol failed the test of time. Br. J . Urol., 66, 164169. Wall, L. L. and Stanton, S. L. (1989). Transvesical phenol injection of pelvic nerve plexuses in females with refractory urge incontinence. Br. J . Urol.,63,465-468.

The Authors C. R. Chapple, MD, FRCS, Senior Registrar. S. J. Hampson, FRCS, Registrar. R. T. Turner-Warwick, DSc, MRCP, FRCS, FACS, FRCOG, Consultant Urologist. P. H. L. Worth, FRCS, Consultant Urologist. Requests for reprints to: C. R. Chapple, Department of Urology, Middlesex Hospital, Mortimer Street, London W I N 8AA.

Subtrigonal phenol injection. How safe and effective is it?

A series of 24 patients underwent 27 transtrigonal phenol injections for the treatment of bladder instability. Only 2 of 18 patients with detrusor ins...
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