Noninvasive Sacral Neuromodulation in Children and Adolescents: A Case-Control Study of Patients With Chronic Refractory Constipation.

OBJECTIVES: In adult patients with chronic refractory constipation, invasive sacral neuromodulation (SNM) has been applied successfully. There is a need for less invasive solutions while providing comparable therapeutic effects in children and adolescents. We present a prospective, interventional case-control study on the application of noninvasive SNM. MATERIALS AND METHODS: Patients with chronic constipation refractory to conservative treatment were prospectively included in the study from 2018 to 2021 and randomized to either SNM (SNM group: single current stimulation for 24 h/d, frequency 15 Hz, pulse width 210 µs, intensity 1-10 mA) or conventional treatment (controls: full range of pharmacologic and nonpharmacologic options). Treatment was conducted for 12 weeks. Treatment effects were collected with specialized questionnaires and quality-of-life analysis (KINDLR). Outcome variables were defecation frequency, stool consistency, fecal incontinence (FI) episodes, and abdominal pain. RESULTS: Analysis was conducted in 28 patients with SNM and 31 controls (median age 7.0, range 3-16 years). Overall responsiveness to treatment was 86% of the SNM group and 39% of the control group (p < 0.001). All outcome variables were positively influenced by SNM treatment. Defecation frequency improved in 46% of patients with SNM and in 19% of controls (p = 0.026), as did stool consistency in 57% of patients with SNM and in 26% of controls (p = 0.014). Fecal incontinence was significantly reduced in 76% of patients with SNM (n = 16/21 vs 42% of controls [n = 11/26], p = 0.042). Quality of life improved significantly during SNM treatment (71.32 [baseline] vs 85.00 [after 12 weeks], p < 0.001) and confirmed a positive influence of SNM treatment compared with the control group (85.00 [SNM after 12 weeks] vs 79.29 [controls after 12 weeks], p = 0.047). CONCLUSIONS: Outcome of noninvasive SNM treatment in patients with chronic refractory constipation is better than conventional treatment.

A European snapshot of psychosocial characteristics and patients' perspectives of faecal incontinence-do they correlate with current scoring systems?

PURPOSE: To compare the current clinical scoring systems used to quantify the severity of symptoms of faecal incontinence (FI) to patients' subjective scoring of parameters of psychosocial well-being. METHODS: Patients referred to six European centres for investigation or treatment of symptoms of FI between June 2017 and September 2019 completed a questionnaire that captured patient demographics, incontinence symptoms using St. Mark's Incontinence score (SMIS) and ICIQ-B, psychological well-being (HADS, Hospital Anxiety and Depression Scale), and social interaction (a three-item loneliness scale). RESULTS: Three hundred eighteen patients completed questionnaires (62 men, mean age 58.7). Sixty percent of the respondents were aged under 65. Median SMIS was 15 (11-18), ICIQ-B bowel pattern was 8 (6-11) and bowel control was 17 (13-22), similar across all demographic groups; however, younger patients were more likely to experience symptoms of depression and anxiety (HADS score > 10, 65.2% of patients age < 65 vs 54.9% of those ages > = 65, p = 0.03) with lower quality of life (ICIQ-B QoL, median score 19 (14-23)) vs age > = 65 (16 (11-21) (p < 0.005)). On loneliness score 25.5% reported often feeling isolated from others. One of the most significant concerns by patients was the fear and embarrassment related to unpredictable episodes of incontinence. CONCLUSION: The SMIS remains a useful tool for quantifying incontinence symptoms but may underestimate the psychosocial morbidity associated with unpredictable episodes of incontinence. Interventions aimed at decreasing anxiety and to address feelings of disgust may be helpful for a significant number of patients requiring treatment for FI.

The science behind programming algorithms for sacral neuromodulation.

AIM: Sacral neuromodulation (SNM) is a widely adopted treatment for overactive bladder, non-obstructive urinary retention and faecal incontinence. In the majority, it provides sustained clinical benefit. However, it is recognized that, even for these patients, stimulation parameters (such as amplitude, electrode configuration, frequency and pulse width) may vary at both initial device programming and at reprogramming, the latter often being required to optimize effectiveness. Although some recommendations exist for SNM programming, the scientific data to support them are understood by few clinicians. METHODS: This is a narrative review of the literature covering some of the science behind stimulating a mixed peripheral nerve and available preclinical data in the field of SNM. It covers electrode configuration, amplitude, frequency, pulse width and cycling considerations. The review is targeted at clinicians with an interest in the field and does not seek to provide exhaustive detail on basic neuroscience. RESULTS AND CONCLUSIONS: Knowledge of the science of neuromodulation provides some guiding principles for programming but these are broad. These principles are not refuted by preclinical data but specific parameters in clinical use are not strongly supported by animal data, even after the limitations of small and large animal models are considered. The review presents a shortlist of programming principles on a theoretical basis but acknowledges that current practice is as much derived from evolved experience as science.

Reprogramming Sacral Neuromodulation for Sub-Optimal Outcomes: Evidence and Recommendations for Clinical Practice.

OBJECTIVES: In some patients treated for urinary or fecal incontinence with sacral neuromodulation (SNM) persistence of symptoms, a reduction in efficacy or adverse effects of stimulation can occur. In such situations, further programming of the SNM device can help resolve problems. Infrequently hardware failure is detected. This article aims to provide practical guidance to solve sub-optimal outcomes (troubleshooting) occurring in the course of SNM therapy. MATERIALS AND METHODS: A systematic literature review was performed. Collective clinical experience from an expert multidisciplinary group was used to form opinion where evidence was lacking. RESULTS: Circumstances in which reprogramming is required are described. Actions to undertake include changes of electrode configuration, stimulation amplitude, pulse frequency, and pulse width. Guidance in case of loss of efficacy and adverse effects of stimulation, developed by a group of European experts, is presented. In addition, various hardware failure scenarios and their management are described. CONCLUSIONS: Reprogramming aims to further improve patient symptoms or ensure a comfortable delivery of the therapy. Initial changes of electrode configuration and adjustment of stimulation parameters can be performed at home to avoid unnecessary hospital visits. A logical and stepwise approach to reprogramming can improve the outcome of therapy and restore patient satisfaction.

Programming Algorithms for Sacral Neuromodulation: Clinical Practice and Evidence-Recommendations for Day-to-Day Practice.

BACKGROUND: In sacral neuromodulation (SNM), stimulation programming plays a key role to achieve success of the therapy. However to date, little attention has been given to the best ways to set and optimize SNM programming during the test and chronic stimulation phases of the procedure. OBJECTIVE: Standardize and make SNM programming easier and more efficient for the several conditions for which SNM is proposed. METHODS: Systematic literature review and collective clinical experience report. RESULTS: The basic principles of SNM programming are described. It covers choice of electrode configuration, stimulation amplitude, pulse frequency and pulse widths, while use of cycling is also briefly discussed. Step-by-step practical flow charts developed by a group of 13 European experts are presented. CONCLUSIONS: Programming of SNM therapy is not complex. There are few programming settings that seem beneficial or significantly impact patient outcomes. Only four basic electrode configurations could be identified according to four different options to define the cathode. In a majority of patients, the proposed stimulation parameters will allow a satisfactory improvement for long periods of time. A regular follow-up is, however, necessary to assess and eventually optimize results, as well as to reassure patients.

Chemoradiotherapy with and without deep regional hyperthermia for squamous cell carcinoma of the anus.

PURPOSE: To compare results after chemoradiotherapy with and without deep regional hyperthermia in patients with anal cancer. METHODS: Between 2000 and 2015, a total of 112 consecutive patients with UICC stage I-IV anal cancer received chemoradiotherapy with 5­fluororuracil and mitomycin C (CRT). In case of insufficient tumor response 4-6 weeks after chemoradiotherapy, patients received an interstitial pulsed-dose-rate brachytherapy boost. Additionally, 50/112 patients received hyperthermia treatments (HCRT). RESULTS: Median follow-up was 41 (2-165) months. After 5 years follow-up, overall (95.8 vs. 74.5%, P = 0.045), disease-free (89.1 vs. 70.4%, P = 0.027), local recurrence-free (97.7 vs. 78.7%, P = 0.006), and colostomy-free survival rates (87.7 vs. 69.0%, P = 0.016) were better for the HCRT group. Disease-specific, regional failure-free, and distant metastasis-free survival rates showed no significant differences. The adjusted hazard ratios for death were 0.25 (95% CI, 0.07 to 0.92; P = 0.036) and for local recurrence 0.14 (95% CI, 0.02 to 1.09; P = 0.06), respectively. Grades 3-4 early toxicities were comparable with the exception of hematotoxicity, which was higher in the HCRT group (66 vs. 43%, P = 0.032). Incidences of late side effects were similar with the exception of a higher telangiectasia rate in the HCRT group (38.0 vs. 16.1%, P = 0.009). CONCLUSION: Additional regional hyperthermia improved overall survival, local control, and colostomy rates. Its potential beneficial role has to be confirmed in a prospective randomized setting. Therefore, the HyCAN trial has already been established by our group and is currently recruiting patients (Clinicaltrials.gov identifier: NCT02369939).

Ventral rectopexy with biological mesh for recurrent disorders of the posterior pelvic organ compartment.

PURPOSE: Recurrent prolapse of the posterior pelvic organ compartment presents a management challenge, with the best surgical procedure remaining unclear. We present functional outcome and patient satisfaction after laparoscopic and robotic ventral mesh rectopexy (VMR) with biological mesh in patients with recurrence. METHODS: We analyzed data from 30 patients with recurrent posterior pelvic organ prolapse who underwent VMR with biological mesh from August 2012 to January 2018. Data included patient demographics and intra- and postoperative findings; functional outcome as assessed by Cleveland Clinic Constipation Score (CCCS), Obstructed Defecation Score Longo (ODS), and Cleveland Clinic Incontinence Score (CCIS); and patient satisfaction. RESULTS: CCCS, CCIS, and ODS were significantly improved at 6-12 months postoperatively and at last follow-up. Patient satisfaction (visual analog scale [VAS] 6.7 [0 to 10]), subjective symptoms (+ 3.4 [scale - 5 to + 5]), and quality of life improvement (+ 3.0 [scale from - 5 to + 5]) were high at last follow-up. The rates of morbidity and major complications were 13% and 3%, respectively. There were no mesh-related complications or deaths. Difference in type of previous surgery (abdominal or transanal/perineal) had no significant effect on results. CONCLUSIONS: VMR with biological mesh is a safe and effective option for patients with recurrent posterior pelvic organ prolapse. It reduces functional symptoms, has a low complication rate, and promotes patient satisfaction.

Cap polyposis in children: case report and literature review.

PURPOSE: Cap polyposis is a benign disease of the colon, characterized by inflammatory polyps with a "cap" of inflammatory granulation tissue. Its prevalence is very low, especially in children. METHODS AND RESULTS: A 16-year-old girl presented with frequent bowel movements with mucous discharge and bloody stool, leading to the initial suspicion of chronic inflammatory bowel disease. Results of further investigation by endoscopy and histological examination were consistent with a diagnosis of cap polyposis. Treatment with systemic steroids resulted in symptom improvement. CONCLUSION: A review of the literature shows that cap polyposis can occur at any age, including childhood, with a slight predilection for the male gender. Rectal bleeding and rectal polyps are consistent features in all reported cases. Other typical symptoms include constipation, diarrhea, and abdominal pain. Symptoms may be very similar to those of chronic inflammatory bowel disease, the most important differential diagnosis. The cause of cap polyposis is still unclear, and specific therapy has not as yet been established. Conservative therapeutic measures should be preferred, especially in children.

To what extent is the low anterior resection syndrome (LARS) associated with quality of life as measured using the EORTC C30 and CR38 quality of life questionnaires?

PURPOSE: Treatment of rectal cancer often results in disturbed anorectal function, which can be quantified by the Low Anterior Resection Syndrome (LARS) score. This study investigates the association of impaired anorectal function as measured with the LARS score with quality of life (QoL) as measured with the EORTC-QLQ-C30 and CR38 questionnaires. METHODS: All stoma-free patients who had undergone sphincter-preserving surgery for rectal cancer from 2000 to 2014 in our institution were retrieved from a prospective database. They were contacted by mail and asked to return the questionnaires. QoL was evaluated in relation to LARS and further patient- and treatment factors using univariate and multivariate analysis. RESULTS: Of the eligible patients (n = 331), 261 (78.8%) responded with a complete LARS score. Mean score for global QoL according to the EORTC-QLQ-C30 questionnaire was 63 ± 21 for all patients. If major LARS was present, mean score decreased to 56 ± 19 in contrast to 67 ± 20 in patients with no/minor LARS (p < 0.001). In regression analysis, major LARS was furthermore associated with reduced physical, role, emotional, cognitive and social functioning as well as impaired body image, more micturition problems and poorer future perspective. It was not related to sexual function. The variance explained by major LARS in the differences of QoL was approximately 10%. CONCLUSION: The presence of major LARS after rectal resection for cancer is negatively associated with global health as well as many other aspects of QoL. Preserving anorectal function and treatment of LARS are potential measures to improve QoL in this patient group.

International Continence Society best practice statement for use of sacral neuromodulation.

AIMS: Sacral neuromodulation (SNM) is an accepted therapy for a variety of conditions. However, despite over 20 years of experience, it remains a specialized procedure with a number of subtleties. Here we present the recommendations issued from the International Continence Society (ICS) SNM Consensus Panel. METHODS: Under the auspices of the ICS, eight urologists, three colorectal surgeons and two urogynecologists, covering a wide breadth of geographic and specialty interest representation, met in January 2017 to discuss best practices for neuromodulation. Suggestions for statements were submitted in advance and specific topics were assigned to committee members, who prepared and presented supporting data to the group, at which time each topic was discussed in depth. Best practice statements were formulated based on available data. This document was then circulated to multiple external reviewers after which final edits were made and approved by the group. RESULTS: The present recommendations, based on the most relevant data available in the literature, as well as expert opinion, address a variety of specific and at times problematic issues associated with SNM. These include the use of SNM for a variety of underlying conditions, need for pre-procedural testing, use of staged versus single-stage procedures, screening for success during the trial phase, ideal anesthesia, device implantation, post-procedural management, trouble-shooting loss of device function, and future directions for research. CONCLUSIONS: These guidelines undoubtedly constitute a reference document, which will help urologists, gynecologists, and colorectal surgeons optimize their use of SNM for refractory urinary urgency and frequency, UUI, NOR, and FI.

Outcome of bowel function following anterior resection for rectal cancer-an analysis using the low anterior resection syndrome (LARS) score.

PURPOSE: Severity of anorectal dysfunction after low anterior resection is associated with various patient- and treatment-related factors. We aimed to quantify anorectal dysfunction after treatment for rectal cancer using the low anterior resection syndrome (LARS) score. METHODS: We retrieved from a prospective database 331 eligible patients on whom anterior resection for rectal cancer had been performed from 2000 to 2014. All patients were sent a LARS score accompanied by a supplementary questionnaire. Response rate was 78.8% (261 patients). The main outcome measure was the relation of the LARS score to potentially associated patient and treatment factors. Secondary endpoints were further measures that reflect anorectal dysfunction, e.g., Vaizey score. RESULTS: Overall, 144 (55.2%) patients exhibited scores > 20 reflecting minor (n = 51 (19.5%)) or major (n = 93 (35.6%)) LARS. A significant difference for scores > 20 was found for intersphincteric resection (IR, 73.2% affected patients) compared to total mesorectal excision (TME, 58.4%) and partial mesorectal excision (PME, 38.0%, p = 0.001). Radio(chemo)therapy resulted in LARS scores > 20 in 64.6% of patients compared to 43.1% in patients without irradiation (p = 0.001). Type of procedure (TME and IR as compared to PME), radio(chemo)therapy, and younger age were independently associated with LARS in logistic regression analysis. However, younger age remained the only independent factor for higher scores after exclusion of PME. CONCLUSIONS: The LARS score identified a substantial proportion of patients after surgery for rectal cancer with anorectal dysfunction. The extent of surgical procedure is independently associated with the severity of symptoms whereas the role of radiotherapy needs further assessment.

Long-term outcome of sacral neuromodulation for chronic refractory constipation.

PURPOSE: Sacral neuromodulation has been reported as a treatment for severe idiopathic constipation. This study aimed to evaluate the long-term effects of sacral neuromodulation by following patients who participated in a prospective, open-label, multicentre study up to 5 years. METHODS: Patients were followed up at 1, 3, 6, 12, 24, 36, 48 and 60 months. Symptoms and quality of life were assessed using bowel diary, the Cleveland Clinic constipation score and the Short Form-36 quality-of-life scale. RESULTS: Sixty-two patients (7 male, median age 40 years) underwent test stimulation, and 45 proceeded to permanent implantation. Twenty-seven patients exited the study (7 withdrawn consent, 7 loss of efficacy, 6 site-specific reasons, 4 withdrew other reasons, 2 lost to follow-up, 1 prior to follow-up). Eighteen patients (29%) attended 60-month follow-up. In 10 patients who submitted bowel diary, their improvement of symptoms was sustained: the number of defecations per week (4.1 ± 3.7 vs 8.1 ± 3.4, mean ± standard deviation, p < 0.001, baseline vs 60 months) and sensation of incomplete emptying (0.8 ± 0.3 vs 0.2 ± 0.1, p = 0.002). In 14 patients (23%) with Cleveland Clinic constipation score, improvement was sustained at 60 months [17.9 ± 4.4 (baseline) to 10.4 ± 4.1, p < 0.001]. Some 103 device-related adverse events were reported in 27 (61%). CONCLUSION: Benefit from sacral neuromodulation in the long-term was observed in a small minority of patients with intractable constipation. The results should be interpreted with caution given the high dropout and complication rate during the follow-up period.

Sacral Neuromodulation: Standardized Electrode Placement Technique.

INTRODUCTION: Sacral neuromodulation (SNM) (sacral nerve stimulation SNS) has become an established therapy for functional disorders of the pelvic organs. Despite its overall success, the therapy fails in a proportion of patients. This may be partially due to inadequate electrode placement with suboptimal coupling of the electrode and nerve. Based on these assumptions the technique of sacral spinal neuromodulation has been redefined. All descriptions relate to the only currently available system licensed for all pelvic indications (Medtronic Interstim® ). METHOD: An international multidisciplinary working party of ten individuals highly experienced in performing SNM convened two meetings (including live operating) to standardize the implant procedure. This report addresses the main steps to optimal electrode lead placement in temporal sequence. RESULTS: Key elements of the electrode placement are radiological marking, the use of a curved stylet, the entry of the electrode into the sacral foramen and its progression through the foramen, its placement guided by a combination of a typical appearance in fluoroscopy and achieving specific motor/sensory responses with stimulation. The report describes quadripolar electrode placement and then either insertion of a connecting percutaneous extension lead or permanent implantation of the programmable device. CONCLUSION: Standardization of electrode placement may ensure close electrode proximity to the target nerve providing a higher likelihood for optimal effect with less energy consumption (better battery longevity), more programming options with more electrode contacts close to the nerve and reduced likelihood of side-effects. The potentially better clinical outcome needs to be demonstrated.

Identification of Predictive Markers for Response to Neoadjuvant Chemoradiation in Rectal Carcinomas by Proteomic Isotope Coded Protein Label (ICPL) Analysis.

Neoadjuvant chemoradiation (nCRT) is an established procedure in stage union internationale contre le cancer (UICC) II/III rectal carcinomas. Around 53% of the tumours present with good tumor regression after nCRT, and 8%-15% are complete responders. Reliable selection markers would allow the identification of poor or non-responders prior to therapy. Tumor biopsies were harvested from 20 patients with rectal carcinomas, and stored in liquid nitrogen prior to therapy after obtaining patients' informed consent (Erlangen-No.3784). Patients received standardized nCRT with 5-Fluoruracil (nCRT I) or 5-Fluoruracil ± Oxaliplatin (nCRT II) according to the CAO/ARO/AIO-04 protocol. After surgery, regression grading (Dworak) of the tumors was performed during histopathological examination of the specimens. Tumors were classified as poor (Dworak 1 + 2) or good (Dworak 3 + 4) responders. Laser capture microdissection (LCM) for tumor enrichment was performed on preoperative biopsies. Differences in expressed proteins between poor and good responders to nCRT I and II were identified by proteomic analysis (Isotope Coded Protein Label, ICPL™) and selected markers were validated by immunohistochemistry. Tumors of 10 patients were classified as histopathologically poor (Dworak 1 or 2) and the other 10 tumor samples as histopathologically good (Dworak 3 or 4) responders to nCRT after surgery. Sufficient material in good quality was harvested for ICPL analysis by LCM from all biopsies. We identified 140 differentially regulated proteins regarding the selection criteria and the response to nCRT. Fourteen of these proteins were synchronously up-regulated at least 1.5-fold after nCRT I or nCRT II (e.g., FLNB, TKT, PKM2, SERINB1, IGHG2). Thirty-five proteins showed a complete reciprocal regulation (up or down) after nCRT I or nCRT II and the rest was regulated either according to nCRT I or II. The protein expression of regulated proteins such as PLEC1, TKT, HADHA and TAGLN was validated successfully by immunohistochemistry. ICPL is a valid method to identify differentially expressed proteins in rectal carcinoma tissue between poor vs. good responders to nCRT. The identified protein markers may act as selection criteria for nCRT in the future, but our preliminary findings must be reproduced and validated in a prospective cohort.

International validation of the low anterior resection syndrome score.

OBJECTIVE: The aims of this study were to investigate the convergent and discriminative validity and reliability of the low anterior resection syndrome (LARS) score in an international setting. BACKGROUND: The LARS score is a simple self-administered questionnaire measuring bowel dysfunction after rectal cancer surgery. The score is intended to be commonly used in international research and clinical practice in the future. Therefore, a thorough validation in an international setting is of utmost importance. METHODS: The LARS score was translated using methods in keeping with current international recommendations. A total of 801 patients operated for rectal cancer in Sweden, Spain, Germany, and Denmark completed the LARS score questionnaire, including an anchor question assessing the impact of bowel function on quality of life. A subgroup of 218 patients completed the LARS score twice. Data were analyzed per country. RESULTS: The LARS score has demonstrated a high convergent validity in terms of a high correlation between LARS score and quality of life (P < 0.001). Sensitivity ranged from 67.7% to 88.3% and specificity from 58.1% to 86.3%. The LARS score was able to discriminate between groups of patients differing with regard to radiotherapy, surgery, and age (P < 0.05). The score also demonstrated high reliability at test-retest with narrow limits of agreement and no statistically significant difference between scores at the first and second test. CONCLUSIONS: The Swedish, Spanish, German, and Danish versions of the LARS score have proven to be valid and reliable tools for measuring LARS in European rectal cancer patients.

Low anterior resection syndrome and quality of life: an international multicenter study.

BACKGROUND: An increasing number of patients are surviving a diagnosis of rectal cancer. The majority of the patients are treated with the sphincter-sparing surgical procedure low anterior resection, and 50% to 90% of these patients experience bowel dysfunction, known as the low anterior resection syndrome. No previous studies have investigated the association between the low anterior resection syndrome and quality of life in an international setting with the use of a validated instrument for the classification of the low anterior resection syndrome. OBJECTIVE: The aim of this study was to investigate the association between quality of life and the low anterior resection syndrome in European patients who have had rectal cancer. DESIGN: The study was designed as an international cross-sectional study involving 5 centers in 4 European countries. PATIENTS: All patients had undergone low anterior resection for rectal cancer, had no stoma, had no dissemination or recurrence at the time of the study, and were at least 16 months past surgery. INTERVENTIONS: The patients received by mail the Low Anterior Resection Syndrome Score and the quality-of-life questionnaire EORTC QLQ-C30. MAIN OUTCOME MEASURES: Eight subscales were selected to be the focus of this study: global quality of life; physical, role, emotional, and social functioning; fatigue; constipation; and diarrhea. RESULTS: A total of 796 patients were included, which corresponds to a response rate of 75.0%. In comparison with patients without low anterior resection syndrome, patients with major low anterior resection syndrome fared substantially worse in all selected subscales (difference ≥ 10 points, p < 0.01), with the exception of constipation. LIMITATIONS: The cross-sectional design prevents an evaluation of causality. CONCLUSIONS: The quality of life of patients who have had rectal cancer is closely associated with the severity of the low anterior resection syndrome. Therefore, it is important that clinicians and researchers focus on this syndrome to improve the prevention and the treatment of bowel dysfunction and the information given to patients.

Sacral neuromodulation for constipation and fecal incontinence in children and adolescents - study protocol of a prospective, randomized trial on the application of invasive vs. non-invasive technique.

BACKGROUND: A therapeutic effect of sacral neuromodulation (SNM) on fecal incontinence (FI) and quality of life has been proven in adults. SNM is, however, rarely used in pediatric cases. The aim of the study is to investigate effects of SNM in pediatric constipation in a prospective parallel-group trial. METHODS: A monocentric, randomized, unblinded, parallel-group trial is conducted. SNM is conducted in the invasive variant and in an innovative, external approach with adhesive electrodes (enteral neuromodulation, ENM). We include patients with constipation according to the ROME IV criteria and refractory to conventional options. Patients with functional constipation and Hirschsprung's disease are able to participate. Participants are allocated in a 1:1 ratio to either SNM or ENM group. Clinical data and quality of life is evaluated in regular check-ups. Neuromodulation is applied continuously for 3 months (end point of the study) with follow-up-points at 6 and 12 months. Findings are analyzed statistically considering a 5% significance level (p ≤ 0.05). Outcome variables are defined as change in (1) episodes of abdominal pain, (2) episodes of FI, (3) defecation frequency, (4) stool consistency. Improvement of proprioception, influence on urinary incontinence, quality of life and safety of treatment are assessed as secondary outcome variables. We expect a relevant improvement in both study groups. DISCUSSION: This is the first trial, evaluating effects of neuromodulation for constipation in children and adolescents and comparing effects of the invasive and non-invasive application (SNM vs. ENM). TRIAL REGISTRATION: The study is registered with clinicaltrials.gov, Identifier NCT04713085 (date of registration 01/14/2021).