Neuromodulation for fecal incontinence: An effective surgical intervention

Table 1 Effectiveness of neuromodulation in fecal incontinence

Ref.	Sample	Study design	Major findings	Adverse events	Comments
Tjandra et al[9]	120 patients with severe FI (solid or liquid FI > 1/wk) were randomized to 2 groups. Of 60 randomized to test stimulation, 53 received permanent implants. Average age 63 yr; > 90% female. Sphincter defect or scar in 47% of both groups	Single site RCT comparing NRM to optimal medical management	71% of permanently implanted patients (63% of randomized patients – ITT analysis) reported > 50% reduction in FI episodes/wk at 12 mo. FI episodes/wk decreased from 9.5 to 3.1 in SNS group, and not at all in controls. All 4 QOL domains significantly improved in SNS. Anal squeeze pressure was unchanged. SNS significantly different from control on all outcomes	Pain in 6%, seroma in 2%, and excessive tingling in vaginal region in 9%, but no septic complications	Low complication rate and excellent outcomes may be related to this being a single-site study
Wexner et al[11]	Multicenter study. 133 received test stimulation; 120 (90.2%) qualified for permanent implant. Average age 60.5 yr; 92% females. Inclusion required > 2 solid or liquid accidents/wk for > 6 mo and > 12 mo postpartum	Multicenter cohort study in United States, Canada, and Australia. Hypothesis was that > 50% would report > 50% reduction in FI frequency at 12 mo compared to baseline. QOL and safety were secondary endpoints	73% of permanently implanted patients (66% of all undergoing test stimulation – ITT analysis) showed > 50% reduction in FI episodes/wk at 12 mo. FI episodes/wk decreased from 9.4 at baseline to 1.9 at 12 mo. All 4 domains of the FI QOL improved significantly. An IAS defect predicted poorer outcome	Pain in 25.8%, paresthesia in 12.5%, infection in 10.8%
Mellgren et al[12]	See Wexner (2010). 77 patients completed the 36 mo FU assessment	This reports the 36 mo outcomes for the Wexner (2010) study	At 36 mo, 86% of 77 patients available for assessment, but only 55% of 120 enrolled patients, reported > 50% reduction in FI	Pain in 28%, paresthesia in 15%, infection in 10%. 5/120 required device explant and 2 required device replacement	ITT analysis under-estimates efficacy because some patients were lost to FU for reasons unrelated to efficacy
Michelsen et al[16]	177 patients at single Danish hospital. Average age 60. 142 (80%) had positive PNE and 126 received NRM	Uncontrolled case series	In 107 of 111 who still had stimulator in place at 12 mo, Wexner score decreased in 87 (median decrease of 7) and was unchanged or worse in 20. No significant change in anorectal manometry	15 of 126 with permanent implant had device explanted. There were 2 infections requiring explant	ITT analysis was not possible. Many patients were lost to FU
Hollingshead et al[13]	118 patients received PNE, 91 (77%) qualified for NRM; and 86 received NRM	Uncontrolled case series	For all 86, median FI episodes/wk decreased from 8.5 to 1.3 and Wexner score decreased from 15 to 9. In 16% of patients reporting 50% reduction initially, efficacy was lost at median of 11.5 mo	Broken leads in 2. Battery replacement in 7 at mean of 81 mo. No other AEs reported	ITT analysis not possible
Altomare et al[23]	94 patients from 6 hospitals underwent PNE, and 60 qualified for and underwent NRM. Average age 58 yr, 83% female	Uncontrolled case series	Of 60 implanted, 2 died (unrelated) and 6 had devices explanted, leaving 52 for 5 year FU. At 5 yr, 37 (39% by ITT) had > 50% decrease in FI frequency. Squeeze and resting pressures increased, maximum tolerated volume decreased	AEs in 8 patients: electrode displacement in 8; pain in 3, allergic reaction in 1; myocardial infarct in 1; unrelated death in 2	ITT success rate at 5 yr was 40% after adjustment for 2 unrelated deaths
Muñoz-Duyos et al[24]	Spanish study of 47 patients who received PNE, of whom 29 (62%) received NRM. PNE was ineffective in 16 and 3 had technical failures	Uncontrolled case series with median 3 yr FU. Cost analysis was primary focus	At last FU, 14 were continent and 11 had > 50% reductions in FI frequency. QOL significantly improved. Total direct costs for NRM were €371 434, estimated to be €16 181 per quality adjusted life year. No improvement in anal canal pressures	8 patients experienced pain but none required explantation	ITT response rate was 53.2%
Dudding et al[22]	British study of 70 patients who received PNE, of whom 61 had > 50% reduction. At analysis, 51 had received permanent implants, and FU was available for 48. These patients may also be included in the Hollingshead (2011) report	Uncontrolled case series with median 24 mo FU. Primary focus was cost-effectiveness. Direct and indirect costs were estimated by theoretical model of services required rather than on actual costs	At 2 yr FU, 41 of 48 with long-term FU (85.4%) had >50% reduction. Direct costs were estimated at £9795 for SNS compared to £2529 for conservative treatment. The estimated incremental cost- effectiveness ratio was £25 070, which is convenient, being within £30 000 recommended by United Kingdom national guidelines	10/48 had complications including 2 wound infections, 1 lead migration, 5 pain, 2 device failures	ITT response rate was 58.6%. Cost analysis was based on theoretical/ imputed data rather than real costs
Chan et al[19]	60 consecutive patients underwent PNE and 53 received NRM. These were separated into 21 with EAS defect vs 32 with intact EAS. One surgeon did all surgeries	Prospective cohort study comparing those with EAS defect to those with intact sphincter	There was a trend for patients with EAS defect to have worse incontinence and poorer squeeze pressures at baseline and FU, but not significant. Outcomes were similar: At 12 mo FU 68.8% with sphincter disruption vs 72.0% with intact sphincter had > 50% reduction in FI. No differences in anal manometry or QOL outcomes	Seroma in 1/53; pain in 3/53. No AEs required explant	Strong support for hypothesis that NRM is equally effective in patients with EAS defects. ITT responder rate for combined group was 63%
Michelsen et al[28]	20 patients randomized; 19 had complete data	Randomized prospective crossover comparing NRM continuously for 3 wk to NRM on only during waking hours for 3 wk	Wexner and St Mark’s incontinence scores and frequency of soiling were significantly worse during device off period. However, FI frequency was not significantly different between conditions	AEs were not reported	Not directly relevant to efficacy of NRM
Leroi et al[18]	34 consecutive FI patients (31 females) considered, 27 eventually studied, 24 completed the trial	Randomized, double-blind, crossover, controlled trial. All 27 patients underwent NRM then randomized in a double-blind crossover design to stimulator ON vs stimulator OFF for 1-mo interval. Patients while blinded choose to meet the final period of 3 mo ON or OFF	Cleveland Clinic Continence score, frequency of FI and urgency, delay in postponing defecation, subjective feeling of improvement, anal physiology, QOL score all significantly improved in the ON interval compared to the OFF interval	10 out of initial 34 reported AE, 4 device explantations: 3 for pain and 1 for infection	First RCT to show effectiveness of NRM compared to placebo; underpowered sample

AE: Adverse event; EAS: External anal sphincter; FU: Follow-up; IAS: Internal anal sphincter.