BACKGROUND: Limited data have been published on the long-term effectiveness of sacral nerve stimulation or sacral neuromodulation for the treatment of severe fecal incontinence. OBJECTIVE: The aim was to assess the long-term efficacy of treatment by analyzing data from the past 5 years combined with precise tools and data collection for sacral nerve stimulation.
DESIGN: Patients with fecal incontinence were enrolled in a multicenter, prospective study with follow-up at 3, 6, and 12 months after device implantation, and then once a year. Patients selected were those with chronic fecal incontinence who had failed conservative treatment or who had not tried additional conservative treatment
Intervention/Measure: Improvement in weekly fecal incontinence episodes was achieved in greater than or equal to 50% of patients at baseline after administration of standard sacral nerve stimulation therapy during a 14-day experimental stimulation cycle.
Primary observable: Treatment success was defined as patients with ≥ 50% symptomatic improvement in weekly episodes of fecal incontinence by questionnaires administered to patients’ 14-day defecation diaries, quality of life for fecal incontinence, and severity of fecal incontinence. Of all adverse events collected.
RESULTS: A total of 120 patients (110 women, mean age 60.5 years) underwent implantation. Seventy-six of these patients (63%) had a follow-up of at least 5 years (maximum, more than 8 years) and were reported on this basis. Over five years, patients’ weekly fecal incontinence episodes decreased from a mean baseline of 9.1 to 1.7, with 89% (N = 64/72) of patients having ≥50% improvement in fecal incontinence symptoms (P < 0.0001) and 36% (26/72) having complete remission of fecal incontinence symptoms. Significant improvement in quality of life scores for fecal incontinence (N = 70, P<0.0001) was observed at all 4-level baseline levels over five years, and 27 of 76 patients (35.5%) required device repair, replacement, or removal of the implanted chip.
CONCLUSIONS: After 5 years of sacral nerve electrical stimulation device implantation and maintenance, the outcome and quality of life of patients with fecal incontinence improved and the rate of repair, replacement, or removal of sacral nerve stimulation devices was acceptable. However, future efforts should focus on improvements to the device.
Fecal incontinence (FI) is a vexing dilemma that is affecting 8-18% of the adult population.1-3 The most common causative factor is an anterior sphincter defect secondary to obstetric trauma. The traditional method of repair for sphincter injury is sphincter overlap repair.
However, long-term outcomes are poor, and several articles have been reported suggesting that health care workers need to seek alternative therapies to achieve long-term outcomes.
Sacral nerve stimulation (SNS), also known as sacral neuromodulation, was first reported by Matzel et al. in 1995 in The Lancet 8 as a treatment for fecal incontinence. Its remarkable improvement in bowel control function is widely used around the world. In addition, the advantage of sacral nerve stimulation over other treatments is that the chip implantation involves a two-stage process, with the second stage of long-term device implantation occurring after the first stage of the device has been determined to be effective.
Even though the successful application of sacral nerve stimulation for the treatment of fecal incontinence was reported in 1995, few articles have been published for a long time, because many of them lacked rigorous follow-up and effective research tools. The purpose of this study was to perform sacral nerve stimulation by precise means and to collect data in order to evaluate the long-term efficacy of the treatment of fecal incontinence.
Patients and methods
Study design and objectives
This prospective, non-randomized study was conducted from 2002 to 2012 under the supervision and guidance of the U.S. Food and Drug Administration (FDA) at 14 study centers in the U.S. and 1 study center in Canada and 1 study center in Australia in patients with chronic constipation who had failed conservative treatment, had not tried additional conservative treatment, or had not received InterStim’s sacral nerve stimulation therapy (FDA approved March 2011, Medtronic, Minneapolis, Minnesota). The previously published article provides more details on how this study was conducted and is intended to help with the efficacy and safety of the sacral nerve stimulation treatment after the start of the trial and following the scheduled cycle.
The study protocol has been approved by the FDA and a multi-system institutional review board, and the current trial covers 120 patients treated with sacral nerve stimulation. In addition to the long-term stimulation treatment of patients, they will also receive sacral nerve stimulation device implantation for at least five years, with data received up to the time of publication of this article. (Feb. 22, 2012)
Patients in the study
Enrolment in the sacral nerve stimulation treatment required knowledge and consent to the previously described criteria for inclusion and exclusion of cases in order to enter the experimental group. All patients were patients suffering from chronic fecal incontinence, defined as those with >2 episodes of fecal incontinence per week for more than 6 months (1 year after vaginal delivery), who had failed conservative treatment or had not tried additional conservative medical treatment, and who were older than 18 years of age, with no upper age limit specified.
Baseline assessment and follow-up visits
The baseline assessment11,12 involves a phase of sacral nerve stimulation device implantation followed by a 10- to 14-day period of transdermal subchronic stimulation in patients who have been enrolled and have passed the examination in order to observe the effects of their treatment. Patients with ≥50% improvement in fecal incontinence symptoms after chronic treatment device implantation were followed for 1 month, 3 months, 6 months, and annually thereafter until withdrawal from the study for all patients who received implantation. Treatment success was defined as a ≥50% improvement in weekly episodes of fecal incontinence.
Defecation recording
Defecation records were completed after baseline levels of incontinence were established and after the prescribed 10-14 day follow-up to assess treatment efficacy (except for the first month of follow-up), and included five questions regarding defecation: total number of incontinent bowel episodes, urgency of defecation, ability to delay defecation, number of incontinent episodes during sleep, and stool properties. The stool properties were verified and graded according to the Bristol stool classification. Patients were excluded from the baseline when they had watery stools (Bristol 7) or mushy stools (Bristol 6).
Quality of life (score) for fecal incontinence
Patient quality of life was based on assessment at each follow-up visit (except at the 1st month follow-up) by means of the quality of life score questionnaire for fecal incontinence, as previously described.10
Indicators of severity of fecal incontinence
In addition, patients’ personal perceptions and physicians’ rigorous symptom scores based on the fecal incontinence severity index were used. Patients were also asked to rate their own bowel health on a scale of 0-10, with 0 being the worst possible state and 10 being the best. And they were asked to indicate whether they used, protective pads, panty liners, or other protective undergarments.
Adverse events will be collected including those that occur during the sacral nerve excitation test, device implantation, regular or unscheduled follow-up, or other surgical procedures performed during the trial, etc. They will be recorded on a standardized adverse event case report form and included in the analysis. An independent adverse event committee will be responsible for determining the seriousness and interrelatedness of each adverse event, such as device, treatment, or implant procedure.
Statistical Analysis
The software package SAS version 9.2 (SAS Software Institute, Inc., Cali, NC) was used for all data analyses. An accurate two-item test was 1 control group comparing partial weekly fecal incontinence, daily fecal incontinence episodes, or urgent fecal incontinence episodes in 50% of patients with ≥50% reduction in the number of episodes. A more conservative and sensitive analytical experiment was also used to manage and handle the missing data analysis. 5 years of missing weekly fecal incontinence episode data were counted as follows: if a patient discontinued the study due to lack of efficacy of the trial, device/treatment related adverse events, or even circumstances leading to death (whether device or treatment related or not), the patient’s underlying bowel record was transferred directly to the analysis phase .
Alternatively, if a patient interrupts the study, misses 5 years of follow-up, or is unable to complete 5 years of basic defecation records for reasons unrelated to the device or treatment, then the patient’s last defecation record (i.e., the most recent) will be performed instead of the use of the missing 5 years of data.
For the comparison of baseline characteristics, the Wilcoxon rank sum test was applied for data collection and the Fisher Precision Test was applied for data analysis. For comparison between patients with ≥50% improvement or <50% improvement in fecal incontinence over 5 years or those who dropped out due to lack of effective return visits over 5 years.
Changes in measures of symptoms and quality of life of patients with fecal incontinence from the time of enrollment to the 5-year follow-up were observed and evaluated after routine data testing with paired t-tests or Wilcoxon rank sum tests. Patient responses to the specified questions when enrolled and at follow-up will be recorded in summary form.
Device-/treatment-related adverse events were recorded by summarizing the number of adverse events and the percentage of each event experienced by the patient, and the calibration, replacement status, and permanent implantation of the patient’s device. An annual statistical survey was performed using a 3-tier analysis using an exact life table method: 1) device modification or replacement, 2) permanent external implantation of the device, and 3) device calibration,,, replacement, or permanent implantation (by any surgical procedure) of the device.
Results
Patients
A total of 285 patients with chronic fecal incontinence were evaluated for enrollment at 16 centers, 152 of whom were excluded primarily because they did not meet the previously described study criteria for chronic fecal incontinence. 133 patients underwent an acute stimulation trial, and 120 had ≥50% improvement in fecal incontinence episodes during the sacral nerve stimulation phase, and had successful device implantation. Surgical procedures, basic anthropometrics, definition of fecal incontinence, and complications have been previously reported.
Seventy-six of the 120 patients received long-term device implantation and completed at least five years of post-implantation follow-up, which is also the focus of this report. Seventy-four of the 76 patients in this study completed at least five years of follow-up, and some of them also completed six, seven, or even eight years of post-implantation follow-up. (Figure 1)
Forty-four patients withdrew from the study before reaching their 5-year visit time limit. Twenty-eight patients (63.6%) achieved at least a 50% improvement in weekly fecal incontinence episodes at their last follow-up visit (Table 1). 44 patients who withdrew from the study for a number of reasons included local principal investigators who were unable to follow up further due to advanced disease, as well as device-/treatment-related adverse events (AEs) (N = 8), lack of treatment effect (N = 7), death (N = 5), and patients who withdrew for other reasons (N = 10).
Long-term treatment observation of treatment
Efficacy on symptoms of fecal incontinence. Long-term follow-up of most patients showed systematic performance at each follow-up visit after sacral nerve stimulation device implantation, and at 5 years after implantation, 89% (64/72) of patients
In addition, 36% (26/72) of patients had achieved complete control of fecal incontinence at 5 years after implantation. The mean value of weekly fecal incontinence episodes decreased from 9.1 at baseline to 1.7 over five years, (p < 0.0001), and this improvement was observed from the baseline change over the past five years. However, the significance test could not guide follow-up beyond 5 years.
A 5-year sensitivity analysis of treatment effect was used to analyze data on weekly fecal incontinence episodes in 48 patients with fecal incontinence implants who had been lost, based on this approach, using baseline observations for 20 patients and carryover past observations for 28 patients, 69% (83/120) of patients achieved at least 50% improvement in weekly fecal incontinence episodes at baseline (p < 0.0001)
In the compliance study, similar long-term improvements in the number of days per week of fecal incontinence and weekly episodes of urge fecal incontinence were observed for patients for less than 5 years. At 5-year follow-up, 86% of patients (62/72) had a 50% improvement in the number of days of weekly incontinence episodes relative to the previous period (P<0.0001), and 79% (57/72) had at least a 50% improvement in the number of episodes of urge fecal incontinence per week compared to the previous period (P<0.0001), with the majority of patients with fecal incontinence treated with long-term sacral nerve stimulation had sustained improvement in symptoms.
Patients completed 1 to 5 years of documented fecal incontinence treatment (N = 70), and analysis of their response to treatment showed that 62 patients (89%) had ≥50% improvement in symptoms in year 1
Five patients who were not successfully treated in the first year but continued with the treatment successfully improved their fecal incontinence symptoms at the subsequent 5-year follow-up.
Fifty-seven patients showed annual treatment success at the 5-year follow-up of the defecation record after implantation, with 43 patients (75.4%) achieving treatment success at each follow-up, 7 patients achieving treatment success at the 4th of 5 follow-ups, and the remaining 7 patients also achieving success at the 3rd (N = 3), 2nd (N = 2), or 1st (N = 1) of 5 follow-ups.
Comparing baseline characteristics, 64 patients improved ≥50% over 5 years, 15 patients improved <50% over 5 years (N = 8), or those who lacked efficacy and dropped out of 5-year follow-up (N = 7), indicating significance in 2 areas: the mean percentage of partial improvement in test stimuli (90% vs. 80%, p value = 0.0072) and the percentage of patients who improved completely in stimulus tests (47% vs. 7%, p-value= 0.0035, Tables 2 and 3), scatter plots were used to explore the relationship between sacral nerve stimulation and long-term effectiveness, showing the significant improvement in symptoms obtained by patients after long-term effective sacral nerve stimulation.
Impact on quality of life, severity of symptoms, bowel health and pad use
Long-term improvements in quality of life have been previously reported in patients after treatment with sacral nerve stimulation, and the results from the current analysis indicate that the content criteria for the modified fecal incontinence quality of life score, and that patients enrolled in the study were followed and maintained for at least 5 years and then maintained through long-term follow-up in the study (Figure 4), fecal incontinence quality of life scores were statistically significant in all four items after the patients were implanted with the device relative to There was a statistically significant improvement before (Table 4).
FISI (fecal incontinence scores) (both physician scores and patient self-ratings) also decreased after device implantation, and the reduction in scores was sustained at least through the 5-year follow-up of this study (Figure 5). At the 5-year follow-up, the patient’s self-rated FISI decreased from 37.95 at baseline to 28.33 (P<0.0001), and similarly, the physician's score decreased from 38.58 at baseline to 29.26 (P<0.0001) at the 5-year follow-up (Table 5).
In follow-up studies at least 5 years after implantation, patients’ self-measured gut health scores
also improved consistently over time (Figure 6), with a significant improvement in the self-measured gut health score (0-10 scale) from a baseline of 3.55 at baseline to 7.29 after 5 years of implantation (P<0.0001).
At long-term follow-up, the use of pads or panty liners and other underwear protection was also reduced relative to baseline, whereas prior to device implantation, 65% of patients required all forms of underwear liner protection type measures throughout the day for at least 5 years of the follow-up study (Figure 7). In contrast, the number of patients requiring undergarment protection throughout the day decreased to 37% at 5 years post-implantation. In addition, 30% of patients reported no further need for undergarment protection at the 5-year follow-up after implantation, compared to 3% before the device was implanted.
Safety
A total of 120 patients in all experimental groups received 559 device implantations over a period of 0.2 to 9.3 years, with a mean implantation time of 4.7 years and a total of 76 implanted patients with a follow-up of at least 5 years, which was the focus of our study.
This segment had a cumulative total of 468 implanted devices applied, with a mean placement time of 6.2 years, and 44 abandoned device implantation at the 5-year follow-up, with a mean implantation time of 2.1 years. Over the course of the prescribed study, these 76 patients had 307 devices used during at least 5 years of follow-up, of which 218 experienced device/treatment-related adverse effects from implantation.
Table 6 summarizes the device/therapy-related adverse reactions that occurred with the 307 devices placed over the course of the study and itemizes the most common device/therapy-related adverse reactions. ), battery depletion of the neurostimulator (9 cases), diarrhea (8 cases), pain in the extremities (N = 7), adverse changes in stimulation (N = 7), and hip pain (N = 6) Most of these events (80%) could be resolved with non-invasive treatment, other methods such as medication, device reprogramming, or no intervention.
When looking only at adverse events that occurred at least 3 years after implantation, (N = 73), the most common adverse reactions were pain at the implantation site, changes in sensation from stimulation (N = 9), sensory abnormalities (N = 8), battery loss (N = 6), displacement of the implanted device (N = 3), and changes in stimulation-induced discomfort yes (N = 3).
The following device acquisitions are omitted.
Discussion
This study has confirmed the efficacy of SNS at 5 years. We have reported data from studies at years 1 and 3.11,12 However, this is the only study in which the majority of patients were followed up for at least 5 years after device implantation. It is also a large sample with close follow-up to study the efficacy of patient FI and SNS used to treat patients with incontinence. In terms of fecal incontinence, there is no precise definition of “long-term fecal incontinence. Some sphincter overlap repairs reported over a 10-year period represent patients receiving more immediate treatment, but there are no precise preoperative and postoperative data for comparison6,7,17.
In addition, a small number of investigators have reported their long-term >5-year outcomes of fecal incontinence treatment,18,19 but there are no long-term prospective studies and systematic follow-up of a certain number of patients, and not as rigorous as the present study.
We look at some specific (SNS) sacral nerve stimulation treatments from long-term results published by altomare et al [19] who reported a prospective follow-up of 52 out of 60 patients for at least 5 years.
Their results showed that 74% of patients had >50% improvement in fecal incontinence episodes, and although the definition of success varied across multiple cross-sectional studies, my comparative study showed that 89% of patients with fecal incontinence had sustained ≥50% reduction in episodes from baseline, and 36% of patients had fully controllable fecal incontinence symptoms. 164 months), of which 12 of the 23 patients (48%) were reported to have complete control of bowel movements.
Matzel et al [18] were the first to report the use of SNS for fecal incontinence in The Lancet in 1995, and have reported long-term outcomes since then. They documented that 9 of 12 patients were continuously treated with SNS and followed for 9.8 years (range 7-14 years). matzel et al. reported that the median number of weekly fecal incontinence episodes observed in these 9 patients decreased from 9 (range 2-58) to 0 (range 0-29, p = 0.012) relative to baseline, and this report is also similar to our data, which was a reduction in the mean weekly fecal incontinence episodes from 9.1 to 1.7 over 5 years relative to baseline.Thus, the results of these long-term studies of SNS in a limited small sample of patients are also similar to our findings.
There was no difference in baseline demographics between patients with ≥50% improvement in symptoms over 5 years versus those with <50% improvement or those who withdrew from the study due to lack of efficacy. However, the effect of excitement trials requires a validated tool to assess patient response to long-term treatment. More detailed correlations should be found between the performance of the data, in general, and the long-term effects that patients can perceive over the course of the study through the definition of a series of conditioning test stimuli (Figure 3).
The success rate of %89 observed at 5 years after implantation may have been overestimated. Because some patients dropped out of the 5-year study due to lack of efficacy, and 36% of patients had less than 50% improvement in symptoms relative to baseline at the last follow-up visit before they dropped out of the 5-year follow-up. However, a sensitivity analysis estimating patients who dropped out of the study either on the basis of baseline or final follow-up showed a more conservative, but still statistically significant, success rate at 5 years post-implantation of 69%.
An interesting observation is that in the current analysis, 8 patients did not achieve ≥50% improvement in weekly fecal incontinence episodes at year 1 follow-up, but did at year 5 follow-up. Further studies are also looking at why 5 of the 8 patients did not succeed in improving in year 1 but did succeed afterwards. However, it suggests to us that some patients with poor initial implantation of the device can lead to success through the lasting effects of the device.
The other 5 patients who were evaluated as successful in year 1 did not meet the criteria for success in year 5. These patients are also puzzling. Further investigation still has no clear reason to explain this group of patients, and it is interesting to note that they still continue to receive this treatment, which may mean that they feel some efficacy. Similarly, George et al.20 reported that 2 of 23 patients lost efficacy at 48 to 60 months for unknown reasons, but both did not have the implanted device removed. Further studies are needed to understand these 2 response patterns in order to refine the results in patients in the future.
When considering fecal incontinence, improving the patient’s “quality of life (QOL) should be the primary focus, not just improving an absolute number. While some researchers believe that quality of life is difficult to measure exclusively in terms of a final number (e.g., number of episodes of fecal incontinence per week), FIQOL has emerged as an acceptable method for studying QOL (quality of life).
In this study all 4 phases of FIQOL improved in one year and surprisingly lasted more than 5 years. Many of the earlier studies did not include quality of life scores (let alone those specific to fecal incontinence), as the importance of this aspect of the study has probably only begun to become apparent in the last decade. altomare et al19 used the SF36 score, which noted a 39.8% improvement after 5 years of implantation.
This study found that overall, 47 (39.2%) of the 120 patients in the group required modification of device parameters, replacement of the device, or removal of the implanted device. At least 5 years of follow-up, 76 (63.3%) of the 120 patients had functioning devices and were still in the study. In the 5-year study group, 20 cases (26.3%) modified device parameters, replaced the device or removed the coarse implant for reasons that did not include battery wear, etc. Much the same results as those shown in our long-term scripture report of sacral stimulation, matzel et al.18 The study group reported follow-up for at least 7 years, showing that 3 of 12 patients (25%) had pain or neurologic disease due to device position movement, 9 patients had consistently effective devices (75%), and 8 patients had pulse generators that required battery replacement for an average of 7.4 years.
Although battery loss was an expected event, there was still an unexpected incidence of 26.3% of commissioning, device replacement, or device removal, which will need to be further investigated in future studies. While this rate is better than other SNS studies, new technologies should focus on reducing the percentage of such events.
In our study, although there were 307 device-/treatment-related adverse events AES, only 20 were considered serious events. We found it difficult to make comparisons with other published studies because other studies have not performed the rigorous collection and counting of adverse events that was done in this study.
There are several strengths in this study, including its long-term follow-up, the number of patients, the quality of the data, and the use of accepted tools to objectively study the effects of patients before and after treatment. A disadvantage of this study is that it was not a randomized controlled study for the control device. Even if the credibility of the data will be increased in the future, this study is currently FDA approved, used a tight design with rigorous baseline data collection, and underwent regular follow-up for 5 years.
In addition, the ideal control group would be a device implanted without activation, since the implantation process is a 2-stage process and permanent implantation continues only when the exact effect is achieved in stage 1. It is more difficult to make patients in the control group lack therapeutic effect because they do not activate the device after the second stage of device implantation. Another limitation of this study is that there was no pre-set protocol for the device. During follow-up patients were able to adjust the stimulation intensity when they needed to via a portable regulator, and future studies will need to accurately record information on the adjustment parameters , and how it leads to battery depletion.
Conclusion
This prospective study on the long-term durability of SNS treatment demonstrated improvements in treatment outcomes and Q0L quality of life scores through 5 years post-implantation, and the device commissioning rate was at least similar in this study compared to other published studies on SNS. Although battery depletion can be expected, further studies need to focus on reducing device commissioning. the place of SNS therapy among current fecal incontinence treatments needs further study, considering the degree of sustained improvement in fecal incontinence and quality of life scores, SNS is proposed as a treatment for early fecal incontinence.