Transcutaneous electrical acupoint stimulation applied in lower limbs decreases the incidence of paralytic ileus after colorectal surgery: A multicenter randomized controlled trial.

BACKGROUND: Postoperative paralytic ileus prolongs hospitalization duration, increases medical expenses, and is even associated with postoperative mortality; however, effective prevention of postoperative paralytic ileus is not yet available. This trial aimed to assess the preventative effectiveness of transcutaneous electrical acupoint stimulation applied in the lower limbs on postoperative paralytic ileus incidence after colorectal surgery. METHODS: After ethics approval and written informed consent, 610 patients from 10 hospitals who were scheduled for colorectal surgery between May 2018 and September 2019 were enrolled. Patients were randomly allocated into the transcutaneous electrical acupoint stimulation (stimulated on bilateral Zusanli, Shangjuxu, and Sanyinjiao acupoints in lower limbs for 30 minutes each time, total 4 times) or sham (without currents delivered) group with 1:1 ratio. The primary outcome was postoperative paralytic ileus incidence, defined as no flatus for >72 hours after surgery. RESULTS: Compared to the sham treatment, transcutaneous electrical acupoint stimulation lowered the postoperative paralytic ileus incidence by 8.7% (32.3% vs 41.0%, P = .026) and decreased the risk of postoperative paralytic ileus by 32% (OR, 0.68; P = .029). Transcutaneous electrical acupoint stimulation also shortened the recovery time to flatus, defecation, normal diet, and bowel sounds. Transcutaneous electrical acupoint stimulation treatment significantly increased median serum acetylcholine by 55% (P = .007) and interleukin-10 by 88% (P < .001), but decreased interleukin-6 by 47% (P < .001) and inducible nitric oxide synthase by 42% (P = .002) at 72 hours postoperatively. CONCLUSION: Transcutaneous electrical acupoint stimulation attenuated the postoperative paralytic ileus incidence and enhanced gastrointestinal functional recovery, which may be associated with increasing parasympathetic nerve tone and its anti-inflammatory actions.

Clinical Impact of Rectal Hyposensitivity: A Cross-Sectional Study of 2,876 Patients With Refractory Functional Constipation.

INTRODUCTION: Normal bowel function requires intact sensory pathways. Diminished rectal sensation (rectal hyposensitivity [RH]) is associated with constipation, although its clinical importance remains unclear. METHODS: Consecutive patients (aged 18-80) attending a tertiary center (2004-2016) for investigation of refractory functional constipation (Rome IV core criteria defined, applied post hoc) were included. Patients completed a clinical symptom questionnaire and underwent anorectal physiologic investigations, including rectal sensory testing (balloon distension) to determine 3 well-established sensory thresholds. Multivariate regression analyses were performed to evaluate associations between RH, symptomology, and allied physiologic investigations. RESULTS: Of 2,876 patients meeting inclusion criteria, 722 (25%) had RH based on ≥1 elevated sensory thresholds (0: n = 2,154 [74.9%]; 1: n = 327 [11.4%]; 2: n = 209 [7.3%]; and 3: n = 186 [6.5%]). A linear relationship existed between increasing number of elevated sensory thresholds and constipation severity (Cleveland Clinic constipation score: mean difference per threshold [95% confidence interval] 0.69 [0.48-0.90]; P < 0.001). Several symptoms were significantly (P < 0.05) associated with RH including: infrequent defecation (odds ratio 1.29 [1.17-1.42]), painful evacuation (1.15 [1.05-1.27]), prolonged toileting (1.14 [1.05-1.24]), and digitation or enema use (1.18 [1.08-1.30]). On defecography, a "functional" evacuation disorder was also associated with RH (1.37 [1.25-1.50], P < 0.001), as was megarectum (2.52 [2.08-3.05], P < 0.001). DISCUSSION: RH occurs in 25% of patients with refractory functional constipation. Increased number of elevated sensory thresholds is associated with more severe constipation phenotype. These data, in the largest study to date, provide for the first time evidence to show that RH is a major pathophysiologic mechanism in constipation, with recognized clinical impact (http://links.lww.com/AJG/B765).(Equation is included in full-text article.).

Translumbosacral Neuromodulation Therapy for Fecal Incontinence: A Randomized Frequency Response Trial.

INTRODUCTION: Treatments for fecal incontinence (FI) remain unsatisfactory because they do not remedy the underlying multifactorial dysfunction(s) including anorectal neuropathy. The aim of this study was to investigate the optimal dose frequency, clinical effects, and safety of a novel treatment, translumbosacral neuromodulation therapy (TNT), aimed at improving neuropathy. METHODS: Patients with FI were randomized to receive 6 sessions of weekly TNT treatments consisting of 600 repetitive magnetic stimulations over each of 2 lumbar and 2 sacral sites with either 1, 5, or 15 Hz frequency. Stool diaries, FI severity indices, anorectal neurophysiology and sensorimotor function, and quality of life were compared. Primary outcome measure was the change in FI episodes/week. Responders were patients with ≥50% decrease in weekly FI episodes. RESULTS: Thirty-three patients with FI participated. FI episodes decreased significantly (∆ ±95% confidence interval, 4.2 ± 2.8 (1 Hz); 2 ± 1.7 (5 Hz); 3.4 ± 2.5 (15 Hz); P < 0.02) in all 3 groups when compared with baseline. The 1 Hz group showed a significantly higher (P = 0.04) responder rate (91 ± 9.1%) when compared with the 5 Hz group (36 ± 18.2%) or 15 Hz (55 ± 18.2%); no difference was found between the 5 and 15 Hz groups (P = 0.667). Anal neuropathy, squeeze pressure, and rectal capacity improved significantly only in the 1 Hz (P < 0.05) group compared with baseline, but not in other groups. Quality of life domains improved significantly (P < 0.05) with 1 and 5 Hz groups. No device-related serious adverse events were noted. DISCUSSION: TNT significantly improves FI symptoms in the short term, and the 1 Hz frequency was overall better than 5 and 15 Hz. Both anorectal neuropathy and physiology significantly improved, demonstrating mechanistic improvement. TNT is a promising, novel, safe, efficacious, and noninvasive treatment for FI (see Visual Abstract, Supplementary Digital Content 3, http://links.lww.com/AJG/B598).

Mechanisms, Evaluation, and Management of Chronic Constipation.

With a worldwide prevalence of 15%, chronic constipation is one of the most frequent gastrointestinal diagnoses made in ambulatory medicine clinics, and is a common source cause for referrals to gastroenterologists and colorectal surgeons in the United States. Symptoms vary among patients; straining, incomplete evacuation, and a sense of anorectal blockage are just as important as decreased stool frequency. Chronic constipation is either a primary disorder (such as normal transit, slow transit, or defecatory disorders) or a secondary one (due to medications or, in rare cases, anatomic alterations). Colonic sensorimotor disturbances and pelvic floor dysfunction (such as defecatory disorders) are the most widely recognized pathogenic mechanisms. Guided by efficacy and cost, management of constipation should begin with dietary fiber supplementation and stimulant and/or osmotic laxatives, as appropriate, followed, if necessary, by intestinal secretagogues and/or prokinetic agents. Peripherally acting µ-opiate antagonists are another option for opioid-induced constipation. Anorectal tests to evaluate for defecatory disorders should be performed in patients who do not respond to over-the-counter agents. Colonic transit, followed if necessary with assessment of colonic motility with manometry and/or a barostat, can identify colonic dysmotility. Defecatory disorders often respond to biofeedback therapy. For specific patients, slow-transit constipation may necessitate a colectomy. No studies have compared inexpensive laxatives with newer drugs with different mechanisms. We review the mechanisms, evaluation, and management of chronic constipation. We discuss the importance of meticulous analyses of patient history and physical examination, advantages and disadvantages of diagnostic testing, guidance for individualized treatment, and management of medically refractory patients.

Evaluation of the anorectal motor response after percutaneous stimulation of the posterior tibial nerve in patients with fecal incontinence.

BACKGROUND: The effect of posterior tibial nerve stimulation (PTNS) on the mechanisms of anal continence has not been fully demonstrated. The aim of this study was to assess the anal manometric response after percutaneous PTNS in patients with fecal incontinence (FI). METHODS: This was a prospective study in patients with FI undergoing 1 weekly session of percutaneous PTNS for 8 weeks. A clinical assessment (Wexner scale) and a complete study of up to 22 manometric parameters were carried out prior to treatment and 2-4 weeks after the end of treatment. RESULTS: A total of 32 patients were evaluated. After therapy, there was a decrease in the average Wexner score [12.6 (± 5.2) to 9.5 (± 5.2) (P < 0.005)] and an increase in the "anal canal length at rest" [4.55 (± 0.60) to 4.95 (± 0.21) P = 0.004], without observing variations in other manometric parameters. The decrease in the Wexner score was significantly correlated with an increase in the "pressure at 5 cm at rest" after therapy (r = 0.464 P = 0.030). CONCLUSIONS: In our study, PTNS was associated with a significant decrease in the Wexner score and with an increase in the functional length of the anal canal at rest. The improvement in the Wexner scale was correlated with an increase in pressure at rest in the theoretical area of the anorectal junction.

A systematic review of clinical studies on electrical stimulation therapy for patients with neurogenic bowel dysfunction after spinal cord injury.

BACKGROUND: This study aimed to perform a systematic literature review of the clinical trial evidence on electrical stimulation for the treatment of neurogenic bowel dysfunction (NBD) after spinal cord injury (SCI). METHODS: Systematic electronic searches were carried out in the PubMed/Medline, EMBASE, Cochrane Central Register of Controlled Trials, and China National Knowledge Infrastructure databases, along with the reference lists in the include studies. Studies were eligible for inclusion if they adopted a controlled clinical design based on human population, the patients suffered from spinal cord injury, the main outcomes were the disorders of bowel function and the intervention was electrical stimulation. Also, the language was limited to English and Chinese. RESULTS: Eleven studies were included in this systematic review, comprising transcutaneous electrical stimulation, transrectal bowel stimulation, sacral nerve stimulation, intravesical electrical stimulation, etc. Of the 11 studies, 3 were randomized controlled trials, 8 were controlled before-and-after trials. The quality of the included studies was moderate bias risk. Most studies revealed that the electrical stimulation was beneficial for the patient with NBD after SCI. CONCLUSIONS: Only 11 small clinical studies with 298 participants have evaluated the efficacy of electrical stimulation for NBD after SCI. Although some studies showed electrical stimulation was benefit for the patient with NBD after SCI, there was currently not enough evidence to support the use of electrical stimulation could improve the clinical symptoms of those patients. Thus, well-designed randomized controlled trials with larger patient population are warranted to establish its benefit in clinical practice in the future.

Robot-guided neuromapping during nerve-sparing taTME for low rectal cancer.

PURPOSE: Intraoperative pelvic neuromapping with electrophysiological evaluation of autonomic nerve preservation during robotic total mesorectal excision (TME) for rectal cancer is conventionally performed by the bedside assistant with a hand-guided probe. Our goal was to return autonomy over the neuromonitoring process to the colorectal surgeon operating the robotic console. METHODS: A recently described prototype microfork electrostimulation probe was evaluated intraoperatively during abdominal robotic-assisted transanal TME (taTME) surgery for low rectal cancer in three consecutive male patients. RESULTS: An intraoperative video demonstrates the good control and maneuverability of the prototype probe with electrophysiological confirmation of bilateral pelvic autonomic nerve preservation. CONCLUSIONS: This study presents the first in situ application of a new microfork probe for fully robot-guided neuromapping in three patients undergoing TME surgery for low rectal cancer.

Short-Term Interferential Transabdominal Electrical Stimulation Did Not Change Oral-Rectal Transit Time in Piglets.

BACKGROUND: Transcutaneous electrical stimulation (TES) using interferential current (IFC) is a new therapeutic treatment for constipation. Clinical studies show that TES-IFC for 3-6 months improves colonic transit, but it is not clear if short-term stimulation affects transit or the effect requires longer to develop. The aim of this study was to determine if TES-IFC for only four days affects oral-rectal transit time in healthy pigs. METHODS: Twenty-two 4-5-week old large white female piglets had transit studies during week 4 and week 5 by placing a capsule containing 18 radiopaque plastic markers in the esophagus under anesthetic followed by x-rays at 6, 30, 54, and 78 hours. Animals were randomly assigned to active or control groups. The active group received TES for 30 min daily for four days. Interferential current was applied through four electrodes (4 × 4 cm), with two para-spinal just below the last rib and two on the belly at the same level. Stimulation was at 4000 Hz and 4080-4160 Hz with currents crossing through the abdominal cavity. RESULTS: Whole bowel transit times ranged from 7.7 to 72.2 hours, stomach transit from <1 to 63 hours, and bowel with rectum transit time from 5 to 53 hours. Transit times were the same for the control (median 28.4 hours) and TES-IFC (23.0 hours) groups in the prestimulation and stimulation weeks (control 23.0, TES-IFC 19.8 hours) with no change within or between groups. CONCLUSION: Four days of half-hour TES-IFC daily in healthy 5-week-old piglets did not change oral-rectal transit time.

Bilateral Posterior Tibial Nerve Stimulation in the Treatment of Rectal Evacuation Disorder: A Preliminary Report.

BACKGROUND: Posterior tibial nerve stimulation influences both motor and sensory pathways, as well as the central nervous system. Stimulation of posterior tibial nerve roots (L4 to S3) could improve stool evacuation through S3 and/or S2 stimulation. OBJECTIVE: This study aimed to assess the efficiency of bilateral posterior tibial nerve stimulation in the treatment of rectal evacuation disorder without anatomic obstruction. DESIGN: This was a prospective case series studying the treatment of patients with obstructed defecation by posterior tibial nerve stimulation. SETTING: The study was conducted at a tertiary referral academic medical center. PATIENTS: Patients with rectal evacuation disorder without anatomic obstruction who were failing maximal conservative treatments were included. INTERVENTION: Thirty minutes of bilateral transcutaneous posterior tibial nerve stimulation was applied 3 times weekly for each patient for 6 consecutive weeks. MAIN OUTCOME MEASURES: The primary end point was the change in the modified obstructed defecation score. Secondary end points were changes in rectal sensitivity volumes (urge to defecate volume and maximal tolerable volume) and quality of life using the Patient Assessment of Constipation-Quality of Life questionnaire. RESULTS: Thirty-six patients (25 women) completed the trial. The mean age of patients was 57.2 years (SD = 14.4 y). No adverse events were reported. Symptomatic successful outcome was reported in 17 patients (47%) and modified obstructed defecation score decreased over 6 weeks (mean decrease = 10 points (95% CI, 8.7-11.3 points); p < 0.0001). Patients with successful outcome (responders) had relatively lower preoperative modified obstructed defecation score compared with patients with unsuccessful outcome (nonresponders). In the successful group, there were significant improvement after 6 weeks in both Patient Assessment of Constipation-Quality of Life score (mean improvement = 43.0 points (95% CI, 35.2-50.7 points); p < 0.0001) and rectal sensitivity (significant reductions in urge to defecate volume (from 258.1 ± 21.2 to 239.6 ± 15.3; p < 0.0001) and maximal tolerable volume (from 304.5 ± 24.8 to 286.8 ± 19.7; p < 0.0001)). No significant change in Patient Assessment of Constipation-Quality of Life or rectal sensitivity was observed in the nonresponders. LIMITATIONS: The study was designed just to proof the concept, but small sample size is a limitation. Another limitation is the short duration of study of only 6 weeks. CONCLUSIONS: Current data showed that bilateral transcutaneous posterior tibial nerve stimulation can improve symptoms in a considerable percentage of patients with obstructed defecation without anatomic obstruction. The procedure is more effective in patients with a less-modified obstructed defecation score. Additional studies are needed to discover the predictive factors for success.

Effectiveness of percutaneous tibial nerve stimulation in managing refractory constipation.

AIM: Chronic constipation can be aetiopathogenically classified into slow transit constipation (STC), rectal evacuation difficulty (RED) or a combination (BOTH). Although the efficacy of percutaneous tibial nerve stimulation (PTNS) in faecal incontinence has been well proved, a current literature search identifies only one study which assessed its effect on constipation. We aimed to evaluate the effectiveness of PTNS in patients with different causes of constipation. METHOD: Thirty-four patients [30 women, median age 50 (20-79) years] with constipation who had previously failed maximal laxative and biofeedback therapy participated in the study. All patients underwent a baseline radio-opaque marker transit study and anorectal physiology examination. All had 12 sessions of PTNS of 30 min per session. A fall in the Wexner constipation score to ≤15 or by ≥5 points was taken as the primary outcome. Secondary outcomes included the results of pre- and post- PTNS transit and anorectal physiology studies. RESULTS: Eleven patients had STC, 14 had RED and nine had BOTH. A response was seen in four patients (1/11 STC, 2/14 RED and 1/9 BOTH). Comparing pre- and post- PTNS, there was no significant change in the mean Wexner score (P = 0.10). There was no change in colonic transit time among the whole population (P = 0.56) or among those with STC (P = 0.47). There was no improvement in balloon expulsion in the whole group (P = 0.73) or in patients with RED (P = 0.69). CONCLUSION: PTNS is of no benefit to patients with constipation, whatever aetiopathogenic mechanism is responsible for the symptoms.

Does Sacral Nerve Stimulation Improve Continence Through Enhanced Sensitivity of the Anal Canal? A Pilot Study.

BACKGROUND: It has been suggested that the effects of sacral nerve stimulation against fecal incontinence involve neuromodulation at spinal or supraspinal levels. OBJECTIVE: This study aims to investigate the afferent sensory pathways from the anorectum before and during sacral nerve stimulation. DESIGN: This is an explorative study. PATIENTS: Fifteen women with idiopathic fecal incontinence (mean age, 58 ± 12.2 years) were selected. INTERVENTIONS: Cortical evoked potentials were recorded during repeated rapid balloon distension of the rectum and the anal canal both before and during temporary sacral nerve stimulation. Stimuli applied were individualized according to the subjective urge to defecate. MAIN OUTCOME MEASURES: The main outcomes measured were 1) stimulus intensity, 2) latencies and amplitudes of cortical evoked potentials, and 3) spectral content in predefined frequency bands of cortical evoked potentials. RESULTS: The median Wexner fecal incontinence score improved from 15.5 ± 3.6 before to 6.7 ± 5 during sacral nerve stimulation (p < 0.001). Sacral nerve stimulation did not affect the threshold for urge to defecate during rectal distension (p = 0.64) but reduced the threshold from stimulation of the anal canal by 50% (p = 0.03). No statistically significant differences were found in latencies, amplitudes, or spectral analysis. LIMITATIONS: This is a pilot study of limited size. CONCLUSIONS: In patients with idiopathic fecal incontinence, sacral nerve stimulation reduced the threshold for urge to defecate elicited from the anal canal, whereas supraspinal responses remained unaltered. This may suggest that sacral nerve stimulation, at least in part, acts via somatic afferent fibers enhancing anal sensation.

Sacral nerve stimulation enhances early intestinal mucosal repair following mucosal injury in a pig model.

KEY POINTS: Reducing intestinal epithelial barrier (IEB) dysfunctions is recognized as being of major therapeutic interest for various intestinal disorders. Sacral nerve stimulation (SNS) is known to reduce IEB permeability. Here, we report in a pig model that SNS enhances morphological and functional recovery of IEB following mucosal injury induced via 2,4,6-trinitrobenzenesulfonic acid. These effects are associated with an increased expression of tight junction proteins such as ZO-1 and FAK. These results establish that SNS enhances intestinal barrier repair in acute mucosal injury. They further set the scientific basis for future use of SNS as a complementary or alternative therapeutic option for the treatment of gut disorders with IEB dysfunctions such as inflammatory bowel diseases or irritable bowel syndrome. ABSTRACT: Intestinal epithelial barrier (IEB) dysfunctions, such as increased permeability or altered healing, are central to intestinal disorders. Sacral nerve stimulation (SNS) is known to reduce IEB permeability, but its ability to modulate IEB repair remains unknown. This study aimed to characterize the impact of SNS on mucosal repair following 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced lesions. Six pigs were stimulated by SNS 3 h prior to and 3 h after TNBS enema, while sham animals (n = 8) were not stimulated. The impact of SNS on mucosal changes was evaluated by combining in vivo imaging, histological and functional methods. Biochemical and transcriptomic approaches were used to analyse the IEB and mucosal inflammatory response. We observed that SNS enhanced the recovery from TNBS-induced increase in transcellular permeability. At 24 h, TNBS-induced alterations of mucosal morphology were significantly less in SNS compared with sham animals. SNS reduced TNBS-induced changes in ZO-1 expression and its epithelial pericellular distribution, and also increased pFAK/FAK expression compared with sham. Interestingly, SNS increased the mucosal density of neutrophils, which was correlated with an increase in trypsin and TGF-ß1 levels compared with sham. Finally, SNS prevented the TNBS-induced increases in IL-1ß and IL-4 over time that were observed with sham treatment. In conclusion, our results show that SNS enhances mucosal repair following injury. This study highlights novel mechanisms of action of SNS and identifies SNS as a new therapy for diseases with IEB repair disorders.

Transcutaneous Sacral Electrical Stimulation for Chronic Functional Constipation.

BACKGROUND: Transcutaneous sacral nerve stimulation is reported to improve symptoms of fecal incontinence. Chronic constipation may also respond to stimulation, but this is poorly reported in the literature. OBJECTIVE: The study assessed the efficacy of transcutaneous electrical stimulation directly over the sacral nerve roots in chronic constipation. PATIENTS: Chronic functional constipation was established in all patients using the Rome III criteria. SETTING: The therapy was self-administered at home. DESIGN/INTERVENTION: A pilot study was conducted of transcutaneous sacral stimulation given over a 4-week period for 12 hours a day. MAIN OUTCOME MEASURES: Patients were assessed using the Patient Assessment of Constipation Symptoms, the Patient Assessment of Constipation Quality of Life, and the Cleveland constipation tool. A Global Rating of Change measure and a 1-week bowel diary was kept for the final week and compared with baseline. RESULTS: Of the 20 patients recruited (16 female, median age 38.5 years), 80% (16) completed the trial. Five (31%) patients reported at least a point reduction in the Patient Assessment of Constipation Symptoms score, 4 (25%) deteriorated, and 7 (44%) improved by less than one point. Median (interquartile range) Patient Assessment of Constipation Symptoms scores were 2.33 (2.34) at baseline and 2.08 (2.58) at follow-up (p = 0.074). Median scores for the Patient Assessment of Constipation Quality of Life and Cleveland systems were 3.00 (1.64) and 17.15 (18) at baseline and 2.22 (3.04) and 15.31 (12) at follow-up (p = 0.096 and 0.111). One-third of patients reported a positive Global Rating of Change measure, although 68% required concurrent laxatives during the trial. LIMITATIONS: This is a pilot study and is limited by its small sample size. CONCLUSIONS: Continuous transcutaneous sacral stimulation in the short term appears to be ineffective for chronic constipation. Larger well-powered studies with intermittent stimulation regimens are required to investigate this further.

Neurostimulated levator augmentation--a new approach in restoring continence.

PURPOSE: Restoration of continence remains a major challenge in patients after abdominoperineal rectal excision (APE) or with end-stage fecal incontinence. A new surgical technique, the neurostimulated levator augmentation, was introduced for pelvic floor augmentation using dynamic graciloplasty in order to restore anorectal angulation. The aim of this study was to assess feasibility and efficiency. METHODS: From November 2009 to March 2014, n = 17 patients underwent neurostimulated levator augmentation (n = 10 after APE, n = 5 intractable idiopathic fecal incontinence, n = 2 traumatic anal amputation). Gracilis muscle was transposed through the obturator foramen into the pelvic cavity, positioned in a U-shaped sling behind the rectum, fixed to the contralateral os pubis to restore anorectal angulation, and then conditioned by neurostimulation. Questionnaires analyzing function and quality of life were administered. RESULTS: For neurostimulated levator augmentation, four patients suffered from complications that needed operative intervention (n = 3 wound infection, n = 1 colon perforation); three pharmacological treatment and two complications needed no further invasive intervention. One patient died due to causes unrelated to the operation, and no complication required intensive care management. Fecal incontinence in patients with idiopathic incontinence improved significantly after surgery as well as incontinence episodes, urgency, and disease-specific quality of life through all dimensions. Generic quality of life was significantly better after surgery in all patients. After median follow-up of 17 months (2-45), all but one patient would undergo the procedure again. CONCLUSIONS: Neurostimulated levator augmentation was feasible in all patients with acceptable morbidity. It may represent a new therapeutic option in selected patients with intractable fecal incontinence.

Laboratory procedures update on Hirschsprung disease.

OBJECTIVES: The detection of ganglion cells in rectal biopsies of infants or toddlers with severe constipation is routinely performed by pediatric pathologists in many institutions. Hirschsprung disease (HD) is defined by the lack of ganglion cells (aganglionosis). The early recognition and the prompt implementation of surgical procedures obviously protect infants affected with HD from potential life-threatening conditions, including enterocolitis and debilitating constipation. Image-based and non-image-based clinical techniques and some laboratory tests have been reevaluated along the years, but often fragmentarily. Immunohistochemical markers have been increasingly used in pathology laboratories to detect ganglion cells and nerve fibers. Recently, calretinin, a vitamin D-dependent calcium-binding protein with expression in ganglion cells and nerves, has been described as an adjunctive or primary diagnostic test in HD. The aim of the present study was to systematically summarize and update laboratory procedures targeting ganglion cells in rectal biopsies. METHODS: Procedures and tests have been reviewed and values of specificity and sensitivity have been calculated according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. RESULTS: Contrast enema has the lowest sensitivity and specificity of all of the 3-index investigations under the lens: contrast enema, anorectal manometry, and biopsy with histology. The latter procedure seems to have the highest sensitivity and specificity. Acetylcholinesterase staining on fresh-frozen material has been found to have slightly higher rates of sensitivity and specificity when compared with hematoxylin and eosin only. Calretinin staining may be supportive for the diagnosis, although some cases with false-positivity may be of some concern. CONCLUSIONS: Hematoxylin and eosin with or without acetylcholinesterase remains the criterion standard according to our PRISMA-based data. In our opinion, the number of false-positive results with potential overtreatment may limit the increasing advocacy for calretinin staining. Both the "primum non nocere" dictum and the "loss aversion heuristic" need to be satisfied harmoniously by preventing harm from unnecessary surgery.

Temporary sacral nerve stimulation in patients with fecal incontinence owing to rectal hyposensitivity: a prospective, double-blind study.

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.

Sacral nerve stimulation changes rectal sensitivity and biomechanical properties in patients with irritable bowel syndrome.

BACKGROUND: Sacral nerve stimulation (SNS) has been demonstrated to alleviate symptoms and improve quality of life in selected patients with irritable bowel syndrome (IBS). The mechanisms of action, however, remain unknown. The aim of the study was to evaluate the effects of SNS on rectal sensitivity and biomechanical properties in patients with IBS. METHODS: Twenty patients with diarrhea-predominant (n = 11) or mixed (n = 9) IBS were treated with SNS in a controlled, randomized crossover trial. They were randomized to either 1 month of SNS (ON) or placebo (OFF) with the opposite setting for the next month. Sensory and biomechanical parameters were assessed by multimodal rectal stimulation at the end of each period. IBS-specific symptoms were evaluated at baseline and at the end of each treatment period. KEY RESULTS: Cold stimuli were better tolerated in the ON period (19.9 °C[± 0.6]) compared to the OFF period (21.8 °C[± 0.6]; p = 0.03). Significantly lower cross-sectional areas were needed to elicit sensory responses in the ON period (1545 mm(2) [± 95]) compared to the OFF period (1869 mm(2) [± 92]; p = 0.015). The association between reduced sensory threshold and improvement of constipation was of borderline significance (p = 0.05). Wall stiffness was significantly lower in the ON period (192 mmHg[± 10]) compared to the OFF period (234 mmHg[± 10]; p = 0.004). Reduced wall stiffness was significantly associated with improved overall GSRS-IBS symptom score (p = 0.01). Reduced sensory threshold to stretch (p = 0.02) and reduced wall stiffness (p < 0.001) were predictors of the GSRS-IBS symptom score. CONCLUSIONS & INFERENCES: SNS for diarrhea-predominant and mixed IBS relaxes the rectal wall, while making it more sensitive to stretch and less sensitive to cold. Reduced wall stiffness and increased sensitivity to stretch are associated with improved GSRS-IBS symptom score.

Treatment of refractory irritable bowel syndrome with visceral osteopathy: short-term and long-term results of a randomized trial.

OBJECTIVE: In light of the low efficiency of available drugs in treating irritable bowel syndrome (IBS), there has been a growing interest in its alternative therapies. The aim of this study was to evaluate the effectiveness of visceral osteopathy for IBS. METHODS: In total, 31 consecutive refractory IBS patients were prospectively included in a randomized, crossover placebo-controlled study. Qualitative evaluation of depression and four symptoms including constipation, diarrhea, abdominal distension and abdominal pain before and after each phase of the study were conducted using visual analog scales, measures of rectal sensitivity and colonic transit time. One year after the study, the assessment of symptoms was performed again in all patients. RESULTS: Visceral osteopathy was associated with a significant amelioration of self-reported diarrhea, abdominal distension and abdominal pain, while constipation did not change significantly after this therapy. It was also associated with decreased rectal sensitivity, presenting as an increase in threshold volume, constant sensation volume and maximum tolerable volume (P < 0.001). However, no significant evolution of rectal sensitivity was observed when patients underwent placebo manipulations. Modifications of depression and total or segmental colonic transit time were not observed. One year after the end of this trial, symptom scores of diarrhea, abdominal distension and abdominal pain were significantly lower than those at enrollment (P < 0.05). CONCLUSION: This study suggests that visceral osteopathy improves short-term and long-term abdominal distension and pain, and also decreases rectal sensitivity in IBS patients.

Variants of Hirschsprung disease.

Variants of Hirschsprung disease are conditions that clinically resemble Hirschsprung disease, despite the presence of ganglion cells in rectal suction biopsies. The characterization and differentiation of various entities are mainly based on histologic, immunohistochemical, and electron microscopy findings of biopsies from patients with functional intestinal obstruction. Intestinal neuronal dysplasia is histologically characterized by hyperganglionosis, giant ganglia, and ectopic ganglion cells. In most intestinal neuronal dysplasia cases, conservative treatments such as laxatives and enema are sufficient. Some patients may require internal sphincter myectomy. Patients with the diagnosis of isolated hypoganglionosis show decreased numbers of nerve cells, decreased plexus area, as well as increased distance between ganglia in rectal biopsies, and resection of the affected segment has been the treatment of choice. The diagnosis of internal anal sphincter achalasia is based on abnormal rectal manometry findings, whereas rectal suction biopsies display presence of ganglion cells as well as normal acetylcholinesterase activity. Internal anal sphincter achalasia is either treated by internal sphincter myectomy or botulinum toxin injection. Megacystis microcolon intestinal hypoperistalsis is a rare condition, and the most severe form of functional intestinal obstruction in the newborn. Megacystis microcolon intestinal hypoperistalsis is characterized by massive abdominal distension caused by a largely dilated nonobstructed bladder, microcolon, and decreased or absent intestinal peristalsis. Although the outcome has improved in recent years, survivors have to be either maintained by total parenteral nutrition or have undergone multivisceral transplant. This review article summarizes the current knowledge of the aforementioned entities of variant HD.

Percutaneous tibial nerve stimulation (PTNS) in females with faecal incontinence: the impact of sphincter morphology and rectal sensation on the clinical outcome.

BACKGROUND: Percutaneous tibial nerve stimulation (PTNS) is an acceptable second line treatment for patients with faecal incontinence (FI) unresponsive to conservative measures. There is however a paucity of data in the literature regarding its efficacy. The aim of this prospective study was to evaluate the efficacy of PTNS in an exclusively female cohort of patients and to identify factors that may predict treatment response. METHOD: A prospective cohort of female patients with FI underwent evaluation of sphincter morphology, anorectal pressures and rectal sensation as part of their physiologic assessment prior to treatment. PTNS was performed according to a specific departmental protocol. The clinical outcomes measured were: (1) Cleveland Clinic incontinence scores, (2) deferment time and (3) weekly incontinence episodes. Outcomes were compared at baseline and following treatment using appropriate statistical tests. Clinical outcomes were correlated with the results of the anorectal physiology testing (i.e. sphincter morphology, rectal sensation). RESULTS: Eighty-eight female patients with a mean age of 58.0 ± 13.6 years were included in the analysis. FI was predominantly a late consequence of obstetric injury. The mean incontinence score improved from 12.2 ± 4.0 at baseline to 9.1 ± 4.6 following treatment (p < 0.0001). Statistically significant improvements were also seen in the median deferment time and median number of weekly incontinence episodes. Sphincter damage and altered rectal sensation did not appear to influence the outcomes. CONCLUSIONS: PTNS is an effective treatment in female patients with FI. Improvements in clinical outcomes were independent of damage to the anal sphincter complex in patients with normal rectal sensation.