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Temporary sacral nerve stimulation in patients with fecal incontinence owing to rectal hyposensitivity: A prospective, double-blind study
Colon/Rectum Temporary sacral nerve stimulation in patients with fecal incontinence owing to rectal hyposensitivity: A prospective, double-blind study Khaled M. Madbouly, MD, PhD, FACS, FASCRS, MRCS (Glasg) and Ahmed M. Hussein, MCh, DrCh, Alexandria, Egypt
Background. Rectal hyposensitivity (RH) can lead to fecal incontinence (FI). Sacral nerve stimulation (SNS) is known to modulate rectal sensation, but no data about affecting FI owing to RH are available. This prospective study aimed to assess the therapeutic effect of temporary SNS on patients with FI owing to RH. Methods. Twenty-four patients with FI owing to RH had temporary SNS (4 weeks on followed by 1 week off). Before SNS (baseline), after 4 weeks of stimulation (on), and at the end of the off week we recorded first constant sensation (FCS), defecatory desire volume (DDV), maximum tolerated volume (MTV), anal pressures, bowel diaries, Wexner incontinence score, and FI quality-of-life score (FIQOL). Results. There were significant decreases in DDV and MTV during the on-treatment period (P < .0001); this decrease was not significant during the off period. FCS was not significantly affected by SNS. FI episodes significantly improved during the on period in 22 patients (from 5.3 to 1.1 per week; P < .0001) and mean Wexner incontinence score improved from 13.3 to 1.7 (P < .0001). Anal pressures (resting and squeeze) significantly increased during the on period but not during the off period. There was significant improvement in FIQOL during the on period only. Conclusion. SNS can be effective in restoring continence and improving QOL in patients with FI owing to RH. Improved continence might be related to improvement of rectal sensation and/or increased anal pressure. The washout effect of SNS on the continence score, DDV, and MTV after cessation of stimulation needs to be explained. (Surgery 2015;157:56-63.) From the Department of Surgery, University of Alexandria, Alexandria, Egypt
INTACT ANORECTAL SENSATION is fundamental to normal anorectal functions, including defecation and continence. Normally there is a complex interaction between sensory and motor function,1 and abnormalities of either component may result in disorders of evacuation or continence. Rectal No financial support was received for this study. The authors declare no conflicts of interest. The paper was a poster presentation at the ASCRS annual meeting 2014, Holywood, FL. Accepted for publication June 9, 2014. Reprint requests: Khaled M. Madbouly, MD, PhD, FACS, FASCRS, MRCS (Glasg), Department of Surgery, University of Alexandria, El Raml Station, Alexandria, Egypt. E-mail: khaled.madbouly@ alexmed.edu.eg. 0039-6060/$ - see front matter Ó 2015 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.surg.2014.06.003
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hyposensitivity (RH) is a physiologic abnormality that relates to a diminished perception of rectal distension. It is present in 16% of all patients attending for physiologic assessment of anorectal dysfunction, with an equal prevalence among males and females.2 The causes of RH are unknown. Traditionally, RH might reflect impaired afferent nerve function peripherally or centrally. Direct injuries to the pelvic or sacral nerves, diabetes mellitus, multiple sclerosis, and cerebrospinal disease have been implicated. Still we have a considerable percentage of idiopathic RH.3 RH has frequently been reported in patients with chronic constipation and idiopathic fecal incontinence (FI). Moreover, it has been reported to be a predictor of poor outcome in the treatment of FI with biofeedback techniques and surgery.4 However, despite these observations, the presence of RH is not often considered when clinical
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decisions are made regarding the selection of patients with FI for surgery.4 Rectal sensory function is commonly quantified by recording the threshold volumes required to elicit first constant sensation (FCS), urge to defecate volume, and maximum tolerated volume (MTV). RH is defined as an increase in the sensory thresholds beyond the normal range.3,5 In patients with RH, the precise pathophysiologic mechanisms involved in the development of symptoms are unclear; however, in constipation, sensorimotor dysfunction of the rectum,6 reflex (viscero-visceral) inhibition of proximal gut function, and secondary colonic dysmotility (rectocolonic inhibitory reflexes) are all possible contributing factors.7 Although FI might be the result of internal anal sphincter relaxation, owing to a chronic rectoanal reflex inhibition without sufficient compensation by external anal sphincter contraction.5 Sacral nerve stimulation (SNS) has been proven repeatedly to be an effective treatment for patients suffering from FI.8,9 Abdel Halim et al10 reported that temporary SNS does not change rectal compliance, but is associated with significant changes to the pressure thresholds of rectal distension. Therefore, SNS may be effective in the treatment of FI owing to RH. Therefore, we have evaluated the efficacy of SNS in patients of FI owing to RH. PURPOSE The aim of this study was to assess prospectively the effect of SNS on FI owing to RH. PATIENTS AND METHODS The current study prospectively included 24 adult patients with FI owing to RH operated in the period from February to October 2013. Patients were recruited consecutively from those failing conservative biofeedback treatments and attending the units of Colon and Rectal Surgery at two tertiary referral centers (Health Insurance Institute and Alexandria University Hospital) to undergo investigation for FI a >4-year period from June 2009 to December 2013. FI was defined as patients with a Wexner incontinence score of >10.11 RH was defined as $2 of 3 abnormal values of FCS, defecatory desire volume (DDV), and MTV compared with departmental control ranges for normal persons. Ethics approval was granted by the Alexandria University Ethics Committee and all patients provided written consent to participate before any intervention. The study was entered on to the International Clinical Trials Database before starting operations in 2013 (Trial ID: ACTRN12613000099729).
Madbouly and Hussein 57
Exclusion criteria included age (<16), diabetic neuropathy, pudendal nerve neuropathy (pudendal nerve terminal motor latency >2.2 ms), multiple sclerosis, Parkinson disease, stroke, bleeding disorders, and cardiac pacemakers. In addition, patients were excluded if they had external anal sphincter injury, sphincter denervation, rectal prolapse, Hirschsprung disease, inflammatory bowel disease, were pregnant, or had severe cardiac disease or chronic renal failure. All patients undergoing SNS were symptomatic for $2 years, and all conservative measures, including dietary, pharmacologic, and biofeedback treatments, had failed. SNS methods. Temporary stimulation was performed with unilateral percutaneous nerve evaluation performed by insertion of a stimulating electrode (3065USC; Medtronic, Minneapolis, MN) into the S3 sacral foramen under local anesthesia.12 Default stimulation parameters were set at 210-microsecond pulse width, 15-Hz frequency, and a subsensory amplitude ranging between 0.5 and 10 V. Stimulation was continuous for 4 weeks followed by 1 week off treatment. Successful percutaneous nerve evaluation (on basis of clinical reduction of incontinence episodes by $50% as judged by physician and patient) was followed by the offer of permanent stimulation. Anal manometry and assessment of rectal sensory function. Anorectal manometry using station pull-through perfusion catheter systems by the use of an 8-channel, water-perfused manometry catheter (Synectics, Stockholm, Sweden)13 was done for all patients with evaluation of mean anal resting pressure (MARP) and maximum anal squeezing pressure (MSP). Rectal sensory thresholds to distension were assessed using the intrarectal bag. Patients were asked to report when they had FCS, DDV, and MTV. The volume at each threshold point was recorded for each patient. Patient evaluation. All patients were evaluated preoperatively by clinical interview and examination. The clinical interview included a detailed questionnaire with special reference to frequency of incontinence, stool consistency, and past history of pelvic or anorectal surgery. Preoperative assessment included anorectal physiology studies (measuring MARP, MSP, FCS, DDV, and MTV). Endoanal ultrasonography (10-MHz transducer; Hitachi Medical, Tokyo, Japan) was done by an experienced radiologist to categorize the internal and external anal sphincters as intact or disrupted. Electromyography for anal sphincters was done to exclude patients with sphincter denervation. Grading of incontinence severity was performed
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using the validated the Wexner incontinence score, ranging from 0 (no symptoms) to 20 (most severe symptoms). Impact on quality of life was assessed by 2 items of the validated FI quality-of-life score (FIQOL) score,14 namely depression and embarrassment. It was not possible to assess the other 2 parameters of FIQOL (coping and life style) owing to the short period of stimulation. Study design and outcome. The rational of the study was to assess the efficacy of SNS in treating FI owing to RH. Because there might be a placebo effect in these patients, we chose to stop the stimulation for 1 week after 4 weeks of stimulation. This design allowed for the recording of all variables at 3 time points representing baseline, on treatment, or off treatment. The 5-week duration was selected as the maximum feasible length of time given acceptability to patients and concerns regarding lead infection. Patients were asked to stop all medications during the study period. Patients received normal diet without adding any medications. Patients were discharged from the hospital on the second day and allowed to do their normal daily activity. They were followed up weekly to the end of the study. Postoperative evaluation was done by a research resident. Patients were instructed not to alter stimulation settings. Patients and the research resident were blinded to the on/off sequence by using subsensory stimulation threshold and complete wrapping of the external stimulator by opaque tape to prevent accidental adjustment. Outcome evaluations included the measurement of rectal sensation and scoring of both continence and quality of life using the Wexner and FIQOL scores, respectively. Five-week bowel diaries recorded all symptoms, including the number of incontinence episodes. Statistical analysis. Statistical analysis was performed by XLSTAT 2013.1.01 software. The outcome measure was the normalization of RH between baseline and on periods. Age- and genderspecific normal data have been collected in the database of our department over a period of 16 years (FCS = 101 mL; DDV = 189 mL; MTV = 285 mL); these define the upper limits of thresholds over which RH is diagnosed for each. Because MTV usually showed change in previous studies, we used it to generate a sample size. SNS is expected to change MTV by 50% on treatment versus baseline. Twenty-four patients were required to detect this difference with 80% power at a 5% significance level. Other outcome measures were the changes in the continence and FIQOL scores. Normally distributed quantitative variables are
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expressed as mean values ± standard deviation; non-normal distributed data are presented as median values and ranges. Categorical statistical analysis was performed by a Fisher exact probability test. For scores analysis, the Mann–Whitney U test, or repeated measure analysis of variance, was used where appropriate. Correlative analyses between physiologic and clinical outcomes were not done because of the small numbers. RESULTS Patient demographics. Twenty-four patients (20 males and 4 females) were included in this study. Figure 1 shows the enrollment Consort E-Flowchart. The demographic characteristics and clinical criteria of patients are illustrated in Table I. The mean patient age was 37.1 years (range, 18– 51). Two patients had previous anal surgeries (1 piles and 1 anal fistula), 2 had stapled transanal rectal resection for obstructed defecation (>6 years before SNS), 2 had surgeries for lumber disc prolapse, and 3 patients had a history of menengiocele (none had spinal nerve damage or pudendal nerve abnormality). The Mean duration of symptoms was 5.3 years. Eleven patients had associated symptoms of obstructed defecation. All patients were experiencing weekly episodes of incontinence, and their symptoms were having a significant impact on their quality of life. Mean Wexner score was 13.29 (range, 11–15). Endoanal ultrasonography showed intact sphincters in 22 patients (91.7%), and internal sphincter defects in 2 patients (8.3%). Median stimulation amplitude was 6.3 V (range, 4–10); no patient altered the settings during the trial. Clinical outcomes. Overall, 22 patients (91%) had a significant clinical response to the stimulation (clinical reduction of incontinence episodes by $50% as judged by physician and patient); 2 patients (9%) did not respond. Weekly episodes of incontinence reduced from the mean of 5.3 to 1.06 (P < .0001), and Wexner scores dropped from the mean of 13.29 to 1.7 (P < .0001). Fourteen patients had a Wexner score of zero during stimulation. Nonresponders experienced some reduction in the number of weekly FI episodes (from 5.4 to 3.9; P = .12) and in WS (13.1 to 10.7; P = .766). Table II shows the effect of SNS on the clinical outcome during stimulation (on) and after cessation of stimulation (off). There were significant improvement in both studied scales of FIQOL, evident immediately after implantation (Table II; Fig 2) and continued to improve for the whole period of stimulation. The FIQOL dropped back during the off period.
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Fig 1. The Consort E-Flowchart. IBD, Inflammatory bowel disease.
Table I. Patients’ characteristics before sacral nerve stimulation (SNS) Character
SNS (n = 24)
Mean age Gender F:M Mean duration of symptoms (y) Associated symptoms of obstructed defecation Bowel frequency (mean per week)
37.1 1:5 5.3 11 5.5
Owing to the high response rate (91%), we were unable to assess the influence of the structural integrity of the sphincter, previous anal surgery, history of menengiocele, or disc prolapsed on the clinical outcome. Anal manometry during stimulation, off periods, and in responders. MARP and MASP pressure significantly increased with stimulation from 55 (range, 51–72) to 78 (range, 65–84) cmH2O and from 161 (range, 155–172) to 182 (range, 171– 202) cmH2O, respectively (Table II shows anal pressures changes in the studied group). No increase in
the MARP or MSP was demonstrated during the off period or among nonresponders. The effects of temporary SNS on rectal sensory thresholds are shown in Table III. There was no change in FCS after stimulation; significant treatment effects were observed for both DDV and MTV only during the stimulation period. These effects were marked between baseline and on treatment but were not different between the baseline and off time points, except in MTV, where there remained a significant difference between the baseline and off time points. Among nonresponders (n = 2), this pattern of change in pressures was not seen. The normalization of rectal sensation was obtained in 20 of 24 patients during stimulation and in 6 of 12 patients during the off period. In nonresponders, rectal sensation was not normalized. DISCUSSION The maintenance of continence is a complex process that involves >1 factor. Intact muscular anal sphincter, normal rectal sensory function, and rectal compliance are crucially important.15 In
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Table II. Effect of sacral nerve stimulation on continence and FI quality of life (FIQOL) score Variable Number of gas incontinence episodes per week Number of liquid incontinence episodes per week Number of solid incontinence episodes per week Wexner score FIQOL depression FIQOL embarrassment
Baseline, median (range) 5 4 4 12 2.5 3
(4–11) (3–5) (1–4) (11–15) (2–3) (2–4)
On, median (range) 1 0 0 1 1 1
(0–5) (0–4) (0–3) (0–9) (1–4) (1–4)
Off, median (range)
P value
5 3 1 10 3 2.5
<.0001* <.0001* <.0001* <.0001* .02* .0003*
(3–5) (2–5) (1–4) (7–12) (3–4) (2–4)
*Mann–Whitney U test.
Fig 2. Fecal incontinence quality-of-life score at different points of stimulation. OFF, Off treatment; ON, on treatment; PRE, pretreatment.
patients with fecal incontinence, RH is diagnosed in 10% of the cases.16 RH is thought to contribute to the development of FI owing to impaired evacuation,16-18 relaxation of the internal anal sphincter at volumes lower than that required to induce rectal sensation,19 reduced anal manometric pressures,16 pelvic floor dysfunction, and/or sphincter incompetence, perhaps related to pelvic nerve damage.17 SNS has become widely accepted in the treatment of FI. There are no reported trials of SNS for selected patients with FI with RH. However, Knowles et al20 addressed the effect of SNS on evacuatory dysfunction owing to RH. The current study was undertaken to assess the potential sensory changes after SNS in patients with RH and whether these changes affect the associated FI. The results demonstrated decrease in the volumes associated with urgency (DDV) and maximal tolerated distension (MTV), which might be indicative of changes in rectal wall sensation and/or compliance. However, no changes were noted in FCS volume. The same results were obtained by Holzer et al21 and Kenefick et al.22 Abdel-Halim et al10 studied the effect of SNS on 23 patients (22
females) with FI and found increase in MTV, but no change in DDV or FCS. In contrast, Knowles et al20 found a significant decrease of DDV and MTV after SNS in patients with constipation and RH. After 3 weeks of SNS, Uludag et al23 observed an improvement of rectal perception with a decreased threshold of FCS and decreased MTV. On the other hand, Michelsen et al24 reported an increase of FCS and MTV after 6 months of permanent stimulation. Finally, Roman et al25 observed no change in rectal sensitivity after 3 months of chronic SNS for FI. These discrepancies could reflect the heterogeneity of patients with FI. It seems that SNS leads to change of the rectal sensory volumes toward normal. Among patients with rectal hypersensitivity (usually associated with irritable bowel syndrome), it leads to a decrease in substance P,26 with a resultant increase of rectal sensory volumes, especially MTV. However, in patients with RH, SNS improves sensation with a resultant decrease of DDV and MTV. The time of evaluation could have also affected the changes in rectal sensation. Vaizey et al27 showed that rectal compliance increased after 24 hours of SNS but returned to baseline SNS values after 7 days. Although this was not the case in the current study, it may be applicable with rectal sensation volumes after longer time. Finally, because few patients were included in these series (15–29 patients) and the ranges of FCS, DDV, and MTVs were wide, the discrepancy in the results is evident. The current study has shown definite increases in MARP and voluntary MSP in all responding patients. Most previous studies have demonstrated an increase in the sphincter squeeze pressure with SNS,22,23,28 although some have shown no change.23,29 The increase in MARP (made mainly by the internal anal sphincter) was significant in the current study. This result was contrary to that reported by Ganio et al12 and Vaizey et al,30 where the effect of SNS on the internal anal sphincter function was unclear.
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Table III. Effect of sacral nerve stimulation on rectal sensation volumes and anal pressures Variable Baseline, mean ± STD On, mean ± STD Off, mean ± STD
P value
FCS DDV MTV MARP MSP
.188* <.0001* <.0001* .004* .003*
133.2 270.2 356.8 55.1 161.1
± ± ± ± ±
25.7 40.2 17.1 23.9 39.4
105.1 165.6 273.8 78.3 182.3
± ± ± ± ±
23.6 24.3 17.1 26.8 42.2
116.1 241.8 321.7 61.7 166.7
± ± ± ± ±
25.7 37.5 39.3 27.9 38.7
Baseline, normal On, normal Off, normal 4/24 2/24 2/24 N/A N/A
22/24 22/24 20/24 N/A N/A
10/24 15/24 12/24 N/A N/A
*One-way repeated measures analysis of variance. DDV, Defecatory desire volume; FCS, first constant sensation; MARP, mean anal resting pressure; MSP, mean anal squeezing pressure; MTV, maximum tolerated volume.
Improvement of the sensory function of the rectum, as well as the effect on the anal sphincter muscles, could be responsible for the positive influence of this method on the incontinence score and quality of life.31 In the current study, there were increases in anal resting and squeeze pressures, along with improved rectal sensation, as shown by improvement toward normal of the rectal sensory thresholds. Improved continence might be owing to one or both of them. Moreover, changes in the pelvic floor muscles with SNS may have played a role. We think that if the improvement of continence was mainly owing to increase muscle tone alone, we would see persistence of abnormally high rectal sensory volumes together with disappearance of incontinence which was not the case. We did not do dynamic magnetic resonance imaging after SNS to detect any pelvic floor change; however, regardless of the mechanism behind continence improvement, our results show that SNS improves continence in these patients. A coordination of rectal sensation and contraction of muscle is required for continence. The only way to determine the critical contribution of either of these is to block one or the other, which was outside the scope of this study. The current study aimed to prove the idea that SNS can help patients with FI owing to RH rather than detecting the mechanism(s) of action behind improvement in these patients. We did not consider possible changes in the anal transition zone (ATZ) sensation as a part of the equation for improvement of continence owing to the SNS treatment, because previous studies have shown that preservation or excision of the ATZ does not lead to change in the functional results.32 In addition, studies showed that application of 5% lignocaine gel to the ATZ of normal people does not lead to a change in continence.33 It has been suggested that ATZ sensation is not a critical factor in preserving continence.33
Previous publications suggested that SNS reduces antegrade transport from the ascending colon and an increased retrograde transport from the descending colon.34,35 The effect of SNS on the colon may be a result of neuromodulation at a more central level.36 The Wexner score improved significantly during stimulation, although there remained some improvement during the off-treatment period. This washout effect was also observed for the clinical symptoms and rectal sensory volumes. The same washout effect was observed in a study by Knowles et al20 that addresses the effect of SNS on evacuatory dysfunction and RH. Currently, there is no explanation for this washout effect. During the 5 weeks of follow-up, FIQOL scores improved significantly in the studied categories during stimulation, whereas scores dropped to the pretreatment levels in the off-treatment period. The same results were obtained by Uludag et al37 in a study of 45 patients with FI of different etiologies. Despite these observations, a placebo effect in some patients cannot be ruled out, except after a longer follow-up period, together with further research of the effects of SNS on rectal sensory function. This study aimed to prove the effectiveness of the mechanism rather than definitive statistical power of a clinical trial. The design, which included a small sample size of highly selected patients undergoing only temporary stimulation, reflects this aim. The study thus has limitations: The main interpretative limitation of the study relates to the choice of a highly selected group of patients based on strict clinical and physiologic criteria to lend proof of mechanism (as evidenced by >4 years recruitment of only 24 patients). Although patients were asked to continue keeping the 5-week bowel diary, there may be some missing incontinence episodes, especially among improved patients. A significant methodologic limitation was the need to limit the study to 5 weeks’ duration. Another limitation of our study
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is that we cannot exclude the fact that some of the changes seen may reflect a type II statistical error because of the small number of participants. Absence of dynamic magnetic resonance imaging of pelvic floor after SNS limited our ability to detect changes in the pelvic floor muscles. The fact that the majority of individuals respond to temporary stimulation made it impossible to compare responders and nonresponders or to specify factors affecting good response. The presence of the off-treatment period has helped to reject the concept of a placebo effect of SNS that has been suggested in previous studies.38,39 However, the observed washout effect during the off-treatment period remains unexplained. In conclusion, SNS can be effective in restoring continence and improving QOL among patients with FI owing to RH. Although a placebo effect of SNS could be ruled out, having off-treatment period and patients blinded to the stimulation sequence ameliorated that risk. However, the washout effect of SNS on the continence score, DDV, and MTV after cessation of stimulation still needs to be explained. Improved continence might be related to improvement of rectal sensation and/or increase of anal pressures. Further studies are needed to detect the exact mechanism behind continence improvement. REFERENCES 1. Bielefeldt K, Enck P, Erckenbrecht JF. Sensory and motor function in the maintenance of anal continence. Dis Colon Rectum 1990;33:674-8. 2. Gladman MA, Scott SM, Chan CL, Williams NS, Lunniss PJ. Rectal hyposensitivity: prevalence and clinical impact in patients with intractable constipation and fecal incontinence. Dis Colon Rectum 2003;46:238-46. 3. Gladman MA, Scott SM, Williams NS, Lunniss PJ. Clinical and physiological findings, and possible aetiological factors of rectal hyposensitivity. Br J Surg 2003;90:860-6. 4. Lee TH, Lee JS, Hong SJ, Jeon SR, Kwon SH, Kim WJ, et al. Rectal hyposensitivity and functional anorectal outlet obstruction are common entities in patients with functional constipation but are not significantly associated. Korean J Intern Med 2013;28:54-61. 5. Vasudevan SP, Scott SM, Gladman MA, Lunniss PJ. Rectal hyposensitivity: evaluation of anal sensation in female patients with refractory constipation with and without faecal incontinence. Neurogastroenterol Motil 2007;19:660-7. 6. Gladman MA, Dvorkin LS, Lunniss PJ, Williams NS, Scott SM. Rectal hyposensitivity: a disorder of the rectal wall or the afferent pathway? An assessment using the barostat. Am J Gastroenterol 2005;100:106-14. 7. Dinning PG, Bampton PA, Kennedy ML, Lubowski DZ, King D, Cook IJ. Impaired proximal colonic motor response to rectal mechanical and chemical stimulation in obstructed defecation. Dis Colon Rectum 2005;48: 1777-84.
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8. Altomare DF, Ratto C, Ganio E, Lolli P, Masin A, Villani RD. Long-term outcome of sacral nerve stimulation for fecal incontinence. Dis Colon Rectum 2009;52:11-7. 9. Matzel KE, Lux P, Heuer S, Besendorfer M, Zhang W. Sacral nerve stimulation for faecal incontinence: long-term outcome. Colorectal Dis 2009;11:636-41. 10. Abdel-Halim MR, Crosbie J, Engledow A, Windsor A, Cohen CR, Emmanuel AV. Temporary sacral nerve stimulation alters rectal sensory function: a physiological study. Dis Colon Rectum 2011;54:1134-40. 11. Jorge JM, Wexner SD. Etiology and management of fecal incontinence. Dis Colon Rectum 1993;36:77-97. 12. Ganio E, Luc AR, Clerico G, Trompetto M. Sacral nerve stimulation for treatment of fecal incontinence: a novel approach for intractable fecal incontinence. Dis Colon Rectum 2001;44:619-29. 13. Williams N, Barlow J, Hobson A, Scott N, Irving M. Manometric asymmetry in the anal canal in controls and patients with fecal incontinence. Dis Colon Rectum 1995; 38:1275-80. 14. Rockwood TH, Church JM, Fleshman JW, Kane RL, Mavrantonis C, Thorson AG, et al. Fecal Incontinence Quality of Life Scale: quality of life instrument for patients with fecal incontinence. Dis Colon Rectum 2000;43:9-16. 15. Burgell RE, Bhan C, Lunniss PJ, Scott SM. Fecal incontinence in men: coexistent constipation and impact of rectal hyposensitivity. Dis Colon Rectum 2012;55:18-25. 16. Burgell RE, Scott SM. Rectal hyposensitivity. J Neurogastroenterol Motil 2012;18:373-84. 17. Nurko S, Scott SM. Coexistence of constipation and incontinence in children and adults. Best Pract Res Clin Gastroenterol 2011;25:29-41. 18. Kang HW, Jung HK, Kwon KJ, Song EM, Choi JY, Kim SE, et al. Prevalence and predictive factors of fecal incontinence. J Neurogastroenterol Motil 2012;18:86-93. 19. Sun WM, Read NW, Miner PB. Relation between rectal sensation and anal function in normal subjects and patients with faecal incontinence. Gut 1990;31:1056-61. 20. Knowles CH, Thin N, Gill K, Bhan C, Grimmer K, Lunniss PJ, et al. Prospective randomized double-blind study of temporary sacral nerve stimulation in patients with rectal evacuatory dysfunction and rectal hyposensitivity. Ann Surg 2012;255:643-9. 21. Holzer B, Rosen HR, Novi G, Ausch C, Holbling N, Schiessel R. Sacral nerve stimulation for neurogenic faecal incontinence. Br J Surg 2007;94:749-53. 22. Kenefick NJ. Sacral nerve neuromodulation for the treatment of lower bowel motility disorders. Ann R Coll Surg Engl 2006;88:617-23. 23. Uludag O, Morren GL, Dejong CH, Baeten CG. Effect of sacral neuromodulation on the Rectum. Br J Surg 2005; 92:1017-23. 24. Michelsen HB, Buntzen S, Krogh K, Laurberg S. Rectal volume tolerability and anal pressures in patients with fecal incontinence treated with sacral nerve stimulation. Dis Colon Rectum 2006;49:1039-44. 25. Roman S, Tatagiba T, Damon H, Barth X, Mion F. Sacral nerve stimulation and rectal function: results of a prospective study in faecal incontinence. Neurogastroenterol Motil 2008;20:1127-31. 26. Gooneratne ML, Facer P, Knowles CH, Chan CL, Lunniss PJ, Scott SM, et al. Normalization of substance P levels in rectal mucosa of patients with faecal incontinence treated successfully by sacral nerve stimulation. Br J Surg 2008;95: 477-83.
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27. Vaizey CJ, Kamm MA, Turner IC, Nicholls RJ, Woloszko J. Effects of short term sacral nerve stimulation on anal and rectal function in patients with anal incontinence. Gut 1999;44:407-12. 28. Jarrett ME, Varma JS, Duthie GS, Nicholls RJ, Kamm MA. Sacral nerve stimulation for faecal incontinence in the UK. Br J Surg 2004;91:755-61. 29. Jarrett ME, Matzel KE, Christiansen J, Baeten CG, Rosen H, Bittorf B, et al. Sacral nerve stimulation for faecal incontinence in patients with previous partial spinal injury including disc prolapse. Br J Surg 2005;92:734-9. 30. Vaizey CJ, Kamm MA, Roy AJ, Nicholls RJ. Double-blind crossover study of sacral nerve stimulation for fecal incontinence. Dis Colon Rectum 2000;43:298-302. 31. Gladman MA, Aziz Q, Scott SM, Williams NS, Lunniss PJ. Rectal hyposensitivity: pathophysiological mechanisms. Neurogastroenterol Motil 2009;21:508-16. 32. Keighley MR, Winslet MC, Yoshioka K, Lightwood R. Discrimination is not impaired by excision of the anal transition zone after restorative proctocolectomy. Br J Surg 1987;74:1118-21. 33. Read MG, Read NW. Role of anorectal sensation in preserving continence. Gut 1982;23:345-7.
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34. Dinning PG, Fuentealba SE, Kennedy ML, Lubowski DZ, Cook IJ. Sacral nerve stimulation induces pan-colonic propagating pressure waves and increases defecation frequency in patients with slow-transit constipation. Colorectal Dis 2007;9:123-32. 35. Michelsen HB, Christensen P, Krogh K, Rosenkilde M, Buntzen S, Theil J, et al. Sacral nerve stimulation for faecal incontinence alters colorectal transport. Br J Surg 2008;95:779-84. 36. Blok BF, Groen J, Bosch JL, Veltman DJ, Lammertsma AA. Different brain effects during chronic and acute sacral neuromodulation in urge incontinent patients with implanted neurostimulators. BJU Int 2006;98:1238-43. 37. Uludag O, Melenhorst J, Koch SM, van Gemert WG, Dejong CH, Baeten CG. Sacral neuromodulation: long-term outcome and quality of life in patients with faecal incontinence. Colorectal Dis 2011;13:1162-6. 38. Leroi AM, Parc Y, Lehur PA, Mion F, Barth X, Rullier E, et al. Efficacy of sacral nerve stimulation for fecal incontinence: results of a multicenter double-blind crossover study. Ann Surg 2005;242:662-9. 39. Ripetti V. Efficacy of sacral nerve stimulation for fecal incontinence: results of a multicenter double-blind crossover study. Tech Coloproctol 2006;10:159-60.
Background. Rectal hyposensitivity (RH) can lead to fecal incontinence (FI). Sacral nerve stimulation (SNS) is known to modulate rectal sensation, but no data about affecting FI owing to RH are available. This prospective study aimed to assess the therapeutic effect of temporary SNS on patients with FI owing to RH. Methods. Twenty-four patients with FI owing to RH had temporary SNS (4 weeks on followed by 1 week off). Before SNS (baseline), after 4 weeks of stimulation (on), and at the end of the off week we recorded first constant sensation (FCS), defecatory desire volume (DDV), maximum tolerated volume (MTV), anal pressures, bowel diaries, Wexner incontinence score, and FI quality-of-life score (FIQOL). Results. There were significant decreases in DDV and MTV during the on-treatment period (P < .0001); this decrease was not significant during the off period. FCS was not significantly affected by SNS. FI episodes significantly improved during the on period in 22 patients (from 5.3 to 1.1 per week; P < .0001) and mean Wexner incontinence score improved from 13.3 to 1.7 (P < .0001). Anal pressures (resting and squeeze) significantly increased during the on period but not during the off period. There was significant improvement in FIQOL during the on period only. Conclusion. SNS can be effective in restoring continence and improving QOL in patients with FI owing to RH. Improved continence might be related to improvement of rectal sensation and/or increased anal pressure. The washout effect of SNS on the continence score, DDV, and MTV after cessation of stimulation needs to be explained. (Surgery 2015;157:56-63.) From the Department of Surgery, University of Alexandria, Alexandria, Egypt
INTACT ANORECTAL SENSATION is fundamental to normal anorectal functions, including defecation and continence. Normally there is a complex interaction between sensory and motor function,1 and abnormalities of either component may result in disorders of evacuation or continence. Rectal No financial support was received for this study. The authors declare no conflicts of interest. The paper was a poster presentation at the ASCRS annual meeting 2014, Holywood, FL. Accepted for publication June 9, 2014. Reprint requests: Khaled M. Madbouly, MD, PhD, FACS, FASCRS, MRCS (Glasg), Department of Surgery, University of Alexandria, El Raml Station, Alexandria, Egypt. E-mail: khaled.madbouly@ alexmed.edu.eg. 0039-6060/$ - see front matter Ó 2015 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.surg.2014.06.003
56 SURGERY
hyposensitivity (RH) is a physiologic abnormality that relates to a diminished perception of rectal distension. It is present in 16% of all patients attending for physiologic assessment of anorectal dysfunction, with an equal prevalence among males and females.2 The causes of RH are unknown. Traditionally, RH might reflect impaired afferent nerve function peripherally or centrally. Direct injuries to the pelvic or sacral nerves, diabetes mellitus, multiple sclerosis, and cerebrospinal disease have been implicated. Still we have a considerable percentage of idiopathic RH.3 RH has frequently been reported in patients with chronic constipation and idiopathic fecal incontinence (FI). Moreover, it has been reported to be a predictor of poor outcome in the treatment of FI with biofeedback techniques and surgery.4 However, despite these observations, the presence of RH is not often considered when clinical
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decisions are made regarding the selection of patients with FI for surgery.4 Rectal sensory function is commonly quantified by recording the threshold volumes required to elicit first constant sensation (FCS), urge to defecate volume, and maximum tolerated volume (MTV). RH is defined as an increase in the sensory thresholds beyond the normal range.3,5 In patients with RH, the precise pathophysiologic mechanisms involved in the development of symptoms are unclear; however, in constipation, sensorimotor dysfunction of the rectum,6 reflex (viscero-visceral) inhibition of proximal gut function, and secondary colonic dysmotility (rectocolonic inhibitory reflexes) are all possible contributing factors.7 Although FI might be the result of internal anal sphincter relaxation, owing to a chronic rectoanal reflex inhibition without sufficient compensation by external anal sphincter contraction.5 Sacral nerve stimulation (SNS) has been proven repeatedly to be an effective treatment for patients suffering from FI.8,9 Abdel Halim et al10 reported that temporary SNS does not change rectal compliance, but is associated with significant changes to the pressure thresholds of rectal distension. Therefore, SNS may be effective in the treatment of FI owing to RH. Therefore, we have evaluated the efficacy of SNS in patients of FI owing to RH. PURPOSE The aim of this study was to assess prospectively the effect of SNS on FI owing to RH. PATIENTS AND METHODS The current study prospectively included 24 adult patients with FI owing to RH operated in the period from February to October 2013. Patients were recruited consecutively from those failing conservative biofeedback treatments and attending the units of Colon and Rectal Surgery at two tertiary referral centers (Health Insurance Institute and Alexandria University Hospital) to undergo investigation for FI a >4-year period from June 2009 to December 2013. FI was defined as patients with a Wexner incontinence score of >10.11 RH was defined as $2 of 3 abnormal values of FCS, defecatory desire volume (DDV), and MTV compared with departmental control ranges for normal persons. Ethics approval was granted by the Alexandria University Ethics Committee and all patients provided written consent to participate before any intervention. The study was entered on to the International Clinical Trials Database before starting operations in 2013 (Trial ID: ACTRN12613000099729).
Madbouly and Hussein 57
Exclusion criteria included age (<16), diabetic neuropathy, pudendal nerve neuropathy (pudendal nerve terminal motor latency >2.2 ms), multiple sclerosis, Parkinson disease, stroke, bleeding disorders, and cardiac pacemakers. In addition, patients were excluded if they had external anal sphincter injury, sphincter denervation, rectal prolapse, Hirschsprung disease, inflammatory bowel disease, were pregnant, or had severe cardiac disease or chronic renal failure. All patients undergoing SNS were symptomatic for $2 years, and all conservative measures, including dietary, pharmacologic, and biofeedback treatments, had failed. SNS methods. Temporary stimulation was performed with unilateral percutaneous nerve evaluation performed by insertion of a stimulating electrode (3065USC; Medtronic, Minneapolis, MN) into the S3 sacral foramen under local anesthesia.12 Default stimulation parameters were set at 210-microsecond pulse width, 15-Hz frequency, and a subsensory amplitude ranging between 0.5 and 10 V. Stimulation was continuous for 4 weeks followed by 1 week off treatment. Successful percutaneous nerve evaluation (on basis of clinical reduction of incontinence episodes by $50% as judged by physician and patient) was followed by the offer of permanent stimulation. Anal manometry and assessment of rectal sensory function. Anorectal manometry using station pull-through perfusion catheter systems by the use of an 8-channel, water-perfused manometry catheter (Synectics, Stockholm, Sweden)13 was done for all patients with evaluation of mean anal resting pressure (MARP) and maximum anal squeezing pressure (MSP). Rectal sensory thresholds to distension were assessed using the intrarectal bag. Patients were asked to report when they had FCS, DDV, and MTV. The volume at each threshold point was recorded for each patient. Patient evaluation. All patients were evaluated preoperatively by clinical interview and examination. The clinical interview included a detailed questionnaire with special reference to frequency of incontinence, stool consistency, and past history of pelvic or anorectal surgery. Preoperative assessment included anorectal physiology studies (measuring MARP, MSP, FCS, DDV, and MTV). Endoanal ultrasonography (10-MHz transducer; Hitachi Medical, Tokyo, Japan) was done by an experienced radiologist to categorize the internal and external anal sphincters as intact or disrupted. Electromyography for anal sphincters was done to exclude patients with sphincter denervation. Grading of incontinence severity was performed
58 Madbouly and Hussein
using the validated the Wexner incontinence score, ranging from 0 (no symptoms) to 20 (most severe symptoms). Impact on quality of life was assessed by 2 items of the validated FI quality-of-life score (FIQOL) score,14 namely depression and embarrassment. It was not possible to assess the other 2 parameters of FIQOL (coping and life style) owing to the short period of stimulation. Study design and outcome. The rational of the study was to assess the efficacy of SNS in treating FI owing to RH. Because there might be a placebo effect in these patients, we chose to stop the stimulation for 1 week after 4 weeks of stimulation. This design allowed for the recording of all variables at 3 time points representing baseline, on treatment, or off treatment. The 5-week duration was selected as the maximum feasible length of time given acceptability to patients and concerns regarding lead infection. Patients were asked to stop all medications during the study period. Patients received normal diet without adding any medications. Patients were discharged from the hospital on the second day and allowed to do their normal daily activity. They were followed up weekly to the end of the study. Postoperative evaluation was done by a research resident. Patients were instructed not to alter stimulation settings. Patients and the research resident were blinded to the on/off sequence by using subsensory stimulation threshold and complete wrapping of the external stimulator by opaque tape to prevent accidental adjustment. Outcome evaluations included the measurement of rectal sensation and scoring of both continence and quality of life using the Wexner and FIQOL scores, respectively. Five-week bowel diaries recorded all symptoms, including the number of incontinence episodes. Statistical analysis. Statistical analysis was performed by XLSTAT 2013.1.01 software. The outcome measure was the normalization of RH between baseline and on periods. Age- and genderspecific normal data have been collected in the database of our department over a period of 16 years (FCS = 101 mL; DDV = 189 mL; MTV = 285 mL); these define the upper limits of thresholds over which RH is diagnosed for each. Because MTV usually showed change in previous studies, we used it to generate a sample size. SNS is expected to change MTV by 50% on treatment versus baseline. Twenty-four patients were required to detect this difference with 80% power at a 5% significance level. Other outcome measures were the changes in the continence and FIQOL scores. Normally distributed quantitative variables are
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expressed as mean values ± standard deviation; non-normal distributed data are presented as median values and ranges. Categorical statistical analysis was performed by a Fisher exact probability test. For scores analysis, the Mann–Whitney U test, or repeated measure analysis of variance, was used where appropriate. Correlative analyses between physiologic and clinical outcomes were not done because of the small numbers. RESULTS Patient demographics. Twenty-four patients (20 males and 4 females) were included in this study. Figure 1 shows the enrollment Consort E-Flowchart. The demographic characteristics and clinical criteria of patients are illustrated in Table I. The mean patient age was 37.1 years (range, 18– 51). Two patients had previous anal surgeries (1 piles and 1 anal fistula), 2 had stapled transanal rectal resection for obstructed defecation (>6 years before SNS), 2 had surgeries for lumber disc prolapse, and 3 patients had a history of menengiocele (none had spinal nerve damage or pudendal nerve abnormality). The Mean duration of symptoms was 5.3 years. Eleven patients had associated symptoms of obstructed defecation. All patients were experiencing weekly episodes of incontinence, and their symptoms were having a significant impact on their quality of life. Mean Wexner score was 13.29 (range, 11–15). Endoanal ultrasonography showed intact sphincters in 22 patients (91.7%), and internal sphincter defects in 2 patients (8.3%). Median stimulation amplitude was 6.3 V (range, 4–10); no patient altered the settings during the trial. Clinical outcomes. Overall, 22 patients (91%) had a significant clinical response to the stimulation (clinical reduction of incontinence episodes by $50% as judged by physician and patient); 2 patients (9%) did not respond. Weekly episodes of incontinence reduced from the mean of 5.3 to 1.06 (P < .0001), and Wexner scores dropped from the mean of 13.29 to 1.7 (P < .0001). Fourteen patients had a Wexner score of zero during stimulation. Nonresponders experienced some reduction in the number of weekly FI episodes (from 5.4 to 3.9; P = .12) and in WS (13.1 to 10.7; P = .766). Table II shows the effect of SNS on the clinical outcome during stimulation (on) and after cessation of stimulation (off). There were significant improvement in both studied scales of FIQOL, evident immediately after implantation (Table II; Fig 2) and continued to improve for the whole period of stimulation. The FIQOL dropped back during the off period.
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Fig 1. The Consort E-Flowchart. IBD, Inflammatory bowel disease.
Table I. Patients’ characteristics before sacral nerve stimulation (SNS) Character
SNS (n = 24)
Mean age Gender F:M Mean duration of symptoms (y) Associated symptoms of obstructed defecation Bowel frequency (mean per week)
37.1 1:5 5.3 11 5.5
Owing to the high response rate (91%), we were unable to assess the influence of the structural integrity of the sphincter, previous anal surgery, history of menengiocele, or disc prolapsed on the clinical outcome. Anal manometry during stimulation, off periods, and in responders. MARP and MASP pressure significantly increased with stimulation from 55 (range, 51–72) to 78 (range, 65–84) cmH2O and from 161 (range, 155–172) to 182 (range, 171– 202) cmH2O, respectively (Table II shows anal pressures changes in the studied group). No increase in
the MARP or MSP was demonstrated during the off period or among nonresponders. The effects of temporary SNS on rectal sensory thresholds are shown in Table III. There was no change in FCS after stimulation; significant treatment effects were observed for both DDV and MTV only during the stimulation period. These effects were marked between baseline and on treatment but were not different between the baseline and off time points, except in MTV, where there remained a significant difference between the baseline and off time points. Among nonresponders (n = 2), this pattern of change in pressures was not seen. The normalization of rectal sensation was obtained in 20 of 24 patients during stimulation and in 6 of 12 patients during the off period. In nonresponders, rectal sensation was not normalized. DISCUSSION The maintenance of continence is a complex process that involves >1 factor. Intact muscular anal sphincter, normal rectal sensory function, and rectal compliance are crucially important.15 In
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Table II. Effect of sacral nerve stimulation on continence and FI quality of life (FIQOL) score Variable Number of gas incontinence episodes per week Number of liquid incontinence episodes per week Number of solid incontinence episodes per week Wexner score FIQOL depression FIQOL embarrassment
Baseline, median (range) 5 4 4 12 2.5 3
(4–11) (3–5) (1–4) (11–15) (2–3) (2–4)
On, median (range) 1 0 0 1 1 1
(0–5) (0–4) (0–3) (0–9) (1–4) (1–4)
Off, median (range)
P value
5 3 1 10 3 2.5
<.0001* <.0001* <.0001* <.0001* .02* .0003*
(3–5) (2–5) (1–4) (7–12) (3–4) (2–4)
*Mann–Whitney U test.
Fig 2. Fecal incontinence quality-of-life score at different points of stimulation. OFF, Off treatment; ON, on treatment; PRE, pretreatment.
patients with fecal incontinence, RH is diagnosed in 10% of the cases.16 RH is thought to contribute to the development of FI owing to impaired evacuation,16-18 relaxation of the internal anal sphincter at volumes lower than that required to induce rectal sensation,19 reduced anal manometric pressures,16 pelvic floor dysfunction, and/or sphincter incompetence, perhaps related to pelvic nerve damage.17 SNS has become widely accepted in the treatment of FI. There are no reported trials of SNS for selected patients with FI with RH. However, Knowles et al20 addressed the effect of SNS on evacuatory dysfunction owing to RH. The current study was undertaken to assess the potential sensory changes after SNS in patients with RH and whether these changes affect the associated FI. The results demonstrated decrease in the volumes associated with urgency (DDV) and maximal tolerated distension (MTV), which might be indicative of changes in rectal wall sensation and/or compliance. However, no changes were noted in FCS volume. The same results were obtained by Holzer et al21 and Kenefick et al.22 Abdel-Halim et al10 studied the effect of SNS on 23 patients (22
females) with FI and found increase in MTV, but no change in DDV or FCS. In contrast, Knowles et al20 found a significant decrease of DDV and MTV after SNS in patients with constipation and RH. After 3 weeks of SNS, Uludag et al23 observed an improvement of rectal perception with a decreased threshold of FCS and decreased MTV. On the other hand, Michelsen et al24 reported an increase of FCS and MTV after 6 months of permanent stimulation. Finally, Roman et al25 observed no change in rectal sensitivity after 3 months of chronic SNS for FI. These discrepancies could reflect the heterogeneity of patients with FI. It seems that SNS leads to change of the rectal sensory volumes toward normal. Among patients with rectal hypersensitivity (usually associated with irritable bowel syndrome), it leads to a decrease in substance P,26 with a resultant increase of rectal sensory volumes, especially MTV. However, in patients with RH, SNS improves sensation with a resultant decrease of DDV and MTV. The time of evaluation could have also affected the changes in rectal sensation. Vaizey et al27 showed that rectal compliance increased after 24 hours of SNS but returned to baseline SNS values after 7 days. Although this was not the case in the current study, it may be applicable with rectal sensation volumes after longer time. Finally, because few patients were included in these series (15–29 patients) and the ranges of FCS, DDV, and MTVs were wide, the discrepancy in the results is evident. The current study has shown definite increases in MARP and voluntary MSP in all responding patients. Most previous studies have demonstrated an increase in the sphincter squeeze pressure with SNS,22,23,28 although some have shown no change.23,29 The increase in MARP (made mainly by the internal anal sphincter) was significant in the current study. This result was contrary to that reported by Ganio et al12 and Vaizey et al,30 where the effect of SNS on the internal anal sphincter function was unclear.
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Table III. Effect of sacral nerve stimulation on rectal sensation volumes and anal pressures Variable Baseline, mean ± STD On, mean ± STD Off, mean ± STD
P value
FCS DDV MTV MARP MSP
.188* <.0001* <.0001* .004* .003*
133.2 270.2 356.8 55.1 161.1
± ± ± ± ±
25.7 40.2 17.1 23.9 39.4
105.1 165.6 273.8 78.3 182.3
± ± ± ± ±
23.6 24.3 17.1 26.8 42.2
116.1 241.8 321.7 61.7 166.7
± ± ± ± ±
25.7 37.5 39.3 27.9 38.7
Baseline, normal On, normal Off, normal 4/24 2/24 2/24 N/A N/A
22/24 22/24 20/24 N/A N/A
10/24 15/24 12/24 N/A N/A
*One-way repeated measures analysis of variance. DDV, Defecatory desire volume; FCS, first constant sensation; MARP, mean anal resting pressure; MSP, mean anal squeezing pressure; MTV, maximum tolerated volume.
Improvement of the sensory function of the rectum, as well as the effect on the anal sphincter muscles, could be responsible for the positive influence of this method on the incontinence score and quality of life.31 In the current study, there were increases in anal resting and squeeze pressures, along with improved rectal sensation, as shown by improvement toward normal of the rectal sensory thresholds. Improved continence might be owing to one or both of them. Moreover, changes in the pelvic floor muscles with SNS may have played a role. We think that if the improvement of continence was mainly owing to increase muscle tone alone, we would see persistence of abnormally high rectal sensory volumes together with disappearance of incontinence which was not the case. We did not do dynamic magnetic resonance imaging after SNS to detect any pelvic floor change; however, regardless of the mechanism behind continence improvement, our results show that SNS improves continence in these patients. A coordination of rectal sensation and contraction of muscle is required for continence. The only way to determine the critical contribution of either of these is to block one or the other, which was outside the scope of this study. The current study aimed to prove the idea that SNS can help patients with FI owing to RH rather than detecting the mechanism(s) of action behind improvement in these patients. We did not consider possible changes in the anal transition zone (ATZ) sensation as a part of the equation for improvement of continence owing to the SNS treatment, because previous studies have shown that preservation or excision of the ATZ does not lead to change in the functional results.32 In addition, studies showed that application of 5% lignocaine gel to the ATZ of normal people does not lead to a change in continence.33 It has been suggested that ATZ sensation is not a critical factor in preserving continence.33
Previous publications suggested that SNS reduces antegrade transport from the ascending colon and an increased retrograde transport from the descending colon.34,35 The effect of SNS on the colon may be a result of neuromodulation at a more central level.36 The Wexner score improved significantly during stimulation, although there remained some improvement during the off-treatment period. This washout effect was also observed for the clinical symptoms and rectal sensory volumes. The same washout effect was observed in a study by Knowles et al20 that addresses the effect of SNS on evacuatory dysfunction and RH. Currently, there is no explanation for this washout effect. During the 5 weeks of follow-up, FIQOL scores improved significantly in the studied categories during stimulation, whereas scores dropped to the pretreatment levels in the off-treatment period. The same results were obtained by Uludag et al37 in a study of 45 patients with FI of different etiologies. Despite these observations, a placebo effect in some patients cannot be ruled out, except after a longer follow-up period, together with further research of the effects of SNS on rectal sensory function. This study aimed to prove the effectiveness of the mechanism rather than definitive statistical power of a clinical trial. The design, which included a small sample size of highly selected patients undergoing only temporary stimulation, reflects this aim. The study thus has limitations: The main interpretative limitation of the study relates to the choice of a highly selected group of patients based on strict clinical and physiologic criteria to lend proof of mechanism (as evidenced by >4 years recruitment of only 24 patients). Although patients were asked to continue keeping the 5-week bowel diary, there may be some missing incontinence episodes, especially among improved patients. A significant methodologic limitation was the need to limit the study to 5 weeks’ duration. Another limitation of our study
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is that we cannot exclude the fact that some of the changes seen may reflect a type II statistical error because of the small number of participants. Absence of dynamic magnetic resonance imaging of pelvic floor after SNS limited our ability to detect changes in the pelvic floor muscles. The fact that the majority of individuals respond to temporary stimulation made it impossible to compare responders and nonresponders or to specify factors affecting good response. The presence of the off-treatment period has helped to reject the concept of a placebo effect of SNS that has been suggested in previous studies.38,39 However, the observed washout effect during the off-treatment period remains unexplained. In conclusion, SNS can be effective in restoring continence and improving QOL among patients with FI owing to RH. Although a placebo effect of SNS could be ruled out, having off-treatment period and patients blinded to the stimulation sequence ameliorated that risk. However, the washout effect of SNS on the continence score, DDV, and MTV after cessation of stimulation still needs to be explained. Improved continence might be related to improvement of rectal sensation and/or increase of anal pressures. Further studies are needed to detect the exact mechanism behind continence improvement. REFERENCES 1. Bielefeldt K, Enck P, Erckenbrecht JF. Sensory and motor function in the maintenance of anal continence. Dis Colon Rectum 1990;33:674-8. 2. Gladman MA, Scott SM, Chan CL, Williams NS, Lunniss PJ. Rectal hyposensitivity: prevalence and clinical impact in patients with intractable constipation and fecal incontinence. Dis Colon Rectum 2003;46:238-46. 3. Gladman MA, Scott SM, Williams NS, Lunniss PJ. Clinical and physiological findings, and possible aetiological factors of rectal hyposensitivity. Br J Surg 2003;90:860-6. 4. Lee TH, Lee JS, Hong SJ, Jeon SR, Kwon SH, Kim WJ, et al. Rectal hyposensitivity and functional anorectal outlet obstruction are common entities in patients with functional constipation but are not significantly associated. Korean J Intern Med 2013;28:54-61. 5. Vasudevan SP, Scott SM, Gladman MA, Lunniss PJ. Rectal hyposensitivity: evaluation of anal sensation in female patients with refractory constipation with and without faecal incontinence. Neurogastroenterol Motil 2007;19:660-7. 6. Gladman MA, Dvorkin LS, Lunniss PJ, Williams NS, Scott SM. Rectal hyposensitivity: a disorder of the rectal wall or the afferent pathway? An assessment using the barostat. Am J Gastroenterol 2005;100:106-14. 7. Dinning PG, Bampton PA, Kennedy ML, Lubowski DZ, King D, Cook IJ. Impaired proximal colonic motor response to rectal mechanical and chemical stimulation in obstructed defecation. Dis Colon Rectum 2005;48: 1777-84.
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8. Altomare DF, Ratto C, Ganio E, Lolli P, Masin A, Villani RD. Long-term outcome of sacral nerve stimulation for fecal incontinence. Dis Colon Rectum 2009;52:11-7. 9. Matzel KE, Lux P, Heuer S, Besendorfer M, Zhang W. Sacral nerve stimulation for faecal incontinence: long-term outcome. Colorectal Dis 2009;11:636-41. 10. Abdel-Halim MR, Crosbie J, Engledow A, Windsor A, Cohen CR, Emmanuel AV. Temporary sacral nerve stimulation alters rectal sensory function: a physiological study. Dis Colon Rectum 2011;54:1134-40. 11. Jorge JM, Wexner SD. Etiology and management of fecal incontinence. Dis Colon Rectum 1993;36:77-97. 12. Ganio E, Luc AR, Clerico G, Trompetto M. Sacral nerve stimulation for treatment of fecal incontinence: a novel approach for intractable fecal incontinence. Dis Colon Rectum 2001;44:619-29. 13. Williams N, Barlow J, Hobson A, Scott N, Irving M. Manometric asymmetry in the anal canal in controls and patients with fecal incontinence. Dis Colon Rectum 1995; 38:1275-80. 14. Rockwood TH, Church JM, Fleshman JW, Kane RL, Mavrantonis C, Thorson AG, et al. Fecal Incontinence Quality of Life Scale: quality of life instrument for patients with fecal incontinence. Dis Colon Rectum 2000;43:9-16. 15. Burgell RE, Bhan C, Lunniss PJ, Scott SM. Fecal incontinence in men: coexistent constipation and impact of rectal hyposensitivity. Dis Colon Rectum 2012;55:18-25. 16. Burgell RE, Scott SM. Rectal hyposensitivity. J Neurogastroenterol Motil 2012;18:373-84. 17. Nurko S, Scott SM. Coexistence of constipation and incontinence in children and adults. Best Pract Res Clin Gastroenterol 2011;25:29-41. 18. Kang HW, Jung HK, Kwon KJ, Song EM, Choi JY, Kim SE, et al. Prevalence and predictive factors of fecal incontinence. J Neurogastroenterol Motil 2012;18:86-93. 19. Sun WM, Read NW, Miner PB. Relation between rectal sensation and anal function in normal subjects and patients with faecal incontinence. Gut 1990;31:1056-61. 20. Knowles CH, Thin N, Gill K, Bhan C, Grimmer K, Lunniss PJ, et al. Prospective randomized double-blind study of temporary sacral nerve stimulation in patients with rectal evacuatory dysfunction and rectal hyposensitivity. Ann Surg 2012;255:643-9. 21. Holzer B, Rosen HR, Novi G, Ausch C, Holbling N, Schiessel R. Sacral nerve stimulation for neurogenic faecal incontinence. Br J Surg 2007;94:749-53. 22. Kenefick NJ. Sacral nerve neuromodulation for the treatment of lower bowel motility disorders. Ann R Coll Surg Engl 2006;88:617-23. 23. Uludag O, Morren GL, Dejong CH, Baeten CG. Effect of sacral neuromodulation on the Rectum. Br J Surg 2005; 92:1017-23. 24. Michelsen HB, Buntzen S, Krogh K, Laurberg S. Rectal volume tolerability and anal pressures in patients with fecal incontinence treated with sacral nerve stimulation. Dis Colon Rectum 2006;49:1039-44. 25. Roman S, Tatagiba T, Damon H, Barth X, Mion F. Sacral nerve stimulation and rectal function: results of a prospective study in faecal incontinence. Neurogastroenterol Motil 2008;20:1127-31. 26. Gooneratne ML, Facer P, Knowles CH, Chan CL, Lunniss PJ, Scott SM, et al. Normalization of substance P levels in rectal mucosa of patients with faecal incontinence treated successfully by sacral nerve stimulation. Br J Surg 2008;95: 477-83.
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27. Vaizey CJ, Kamm MA, Turner IC, Nicholls RJ, Woloszko J. Effects of short term sacral nerve stimulation on anal and rectal function in patients with anal incontinence. Gut 1999;44:407-12. 28. Jarrett ME, Varma JS, Duthie GS, Nicholls RJ, Kamm MA. Sacral nerve stimulation for faecal incontinence in the UK. Br J Surg 2004;91:755-61. 29. Jarrett ME, Matzel KE, Christiansen J, Baeten CG, Rosen H, Bittorf B, et al. Sacral nerve stimulation for faecal incontinence in patients with previous partial spinal injury including disc prolapse. Br J Surg 2005;92:734-9. 30. Vaizey CJ, Kamm MA, Roy AJ, Nicholls RJ. Double-blind crossover study of sacral nerve stimulation for fecal incontinence. Dis Colon Rectum 2000;43:298-302. 31. Gladman MA, Aziz Q, Scott SM, Williams NS, Lunniss PJ. Rectal hyposensitivity: pathophysiological mechanisms. Neurogastroenterol Motil 2009;21:508-16. 32. Keighley MR, Winslet MC, Yoshioka K, Lightwood R. Discrimination is not impaired by excision of the anal transition zone after restorative proctocolectomy. Br J Surg 1987;74:1118-21. 33. Read MG, Read NW. Role of anorectal sensation in preserving continence. Gut 1982;23:345-7.
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34. Dinning PG, Fuentealba SE, Kennedy ML, Lubowski DZ, Cook IJ. Sacral nerve stimulation induces pan-colonic propagating pressure waves and increases defecation frequency in patients with slow-transit constipation. Colorectal Dis 2007;9:123-32. 35. Michelsen HB, Christensen P, Krogh K, Rosenkilde M, Buntzen S, Theil J, et al. Sacral nerve stimulation for faecal incontinence alters colorectal transport. Br J Surg 2008;95:779-84. 36. Blok BF, Groen J, Bosch JL, Veltman DJ, Lammertsma AA. Different brain effects during chronic and acute sacral neuromodulation in urge incontinent patients with implanted neurostimulators. BJU Int 2006;98:1238-43. 37. Uludag O, Melenhorst J, Koch SM, van Gemert WG, Dejong CH, Baeten CG. Sacral neuromodulation: long-term outcome and quality of life in patients with faecal incontinence. Colorectal Dis 2011;13:1162-6. 38. Leroi AM, Parc Y, Lehur PA, Mion F, Barth X, Rullier E, et al. Efficacy of sacral nerve stimulation for fecal incontinence: results of a multicenter double-blind crossover study. Ann Surg 2005;242:662-9. 39. Ripetti V. Efficacy of sacral nerve stimulation for fecal incontinence: results of a multicenter double-blind crossover study. Tech Coloproctol 2006;10:159-60.