One-stage implant in sacral neuromodulation for faecal incontinence - short-term outcome from a prospective study.

AIM: Sacral neuromodulation (SNM) is approved for the treatment of faecal incontinence (FI) in a two-stage technique. With standardized implantation, approximately 90% of patients undergo successful Stage I operation and proceed to a permanent implant (Stage II). The aim of this work was to explore the feasibility of SNM as a one-stage procedure and report the 24-week efficacy. METHOD: This study included patients diagnosed with idiopathic FI or FI due to an external anal sphincter defect ≤160° and one or more episodes of FI per week despite maximal conservative therapy. Patients were offered a one-stage procedure if a motor response of the external anal sphincter was achieved in three or more poles with at least one at ≤1.5 mA at lead placement. Patients were followed for 24 weeks. Their evaluation included the Wexner/St Mark's Incontinence Score, Faecal Incontinence Quality of Life score (FIQoL), a visual analogue scale (VAS) for assessing patient satisfaction and a bowel habit diary. RESULTS: Seventy-three patients with a median age of 60 years (interquartile range 50-69 years) completed this prospective study. Episodes of FI were significantly reduced at the 24-week follow-up, from 13 (8-23) at baseline to 2 (0-5) (p-value = 0002). A ≥50% reduction in the number of FI episodes was achieved in 92% of participants. The Wexner score improved significantly from 16 (14-17) at baseline to 9 (5-13) (p-value < 0.001), and the St Mark's score improved significantly from 18 (16-20) to 11 (7-16) (p-value < 0.001). All domains in the FIQoL score and VAS for patient satisfaction improved significantly following the one-stage procedure. CONCLUSION: A one-stage implantation procedure is feasible in selected patients with FI, significantly improving continence, quality of life and patient satisfaction after 24 weeks of follow-up.

Efficacy of Injection of Freshly Collected Autologous Adipose Tissue Into Complex Cryptoglandular Anal Fistulas.

BACKGROUND: Treatment of cryptoglandular anal fistulas with injection of autologous or allogenic adipose tissue-derived mesenchymal stem cells has shown promising results. However, allogenic adipose tissue-derived mesenchymal stem cells are expensive and use of autologous adipose tissue-derived mesenchymal stem cells requires preceding liposuction and isolation of stem cells, time for cell culture, and laboratory facilities. Freshly collected autologous adipose tissue may be an easily available and inexpensive alternative. OBJECTIVE: This study aimed to investigate the efficacy of injection with freshly collected autologous adipose tissue into complex cryptoglandular anal fistulas. DESIGN: Prospective cohort study. SETTING: Single tertiary center for treatment of cryptoglandular fistulas in Denmark. PATIENTS: This study included 77 patients with complex cryptoglandular anal fistulas. INTERVENTIONS: The intervention included injections of freshly collected autologous adipose tissue. Patients not achieving healing after 8 to 12 weeks were offered a second injection. MAIN OUTCOME MEASURES: Primary outcome was fistula healing defined as no symptoms of discharge and no visible external and palpable internal opening by anorectal digital examination at clinical evaluation 6 months after final treatment. Secondary end points were combined clinical and MRI fistula healing, reduced fistula secretion and anal discomfort, and complications to the treatment. RESULTS: Thirty-nine patients (51%) achieved the primary outcome of fistula healing 6 months after their final treatment. Nine patients (12%) experienced reduced secretion and decreased anal discomfort. Thirty-seven patients (48%) achieved combined clinical and MRI fistula healing. Treatment was well tolerated; 5 patients (4%) experienced serious adverse events (infection or bleeding) requiring surgical intervention. LIMITATIONS: No control group was included. CONCLUSION: Injection of freshly collected autologous adipose tissue is a safe treatment of complex cryptoglandular anal fistulas and may be an easily accessible inexpensive alternative to cultured autologous and allogenic adipose tissue-derived mesenchymal stem cells. See Video Abstract at http://links.lww.com/DCR/C45 . EFICACIA DE LA INYECCIN DE TEJIDO ADIPOSO AUTLOGO RECIN RECOLECTADO EN FSTULAS ANALES CRIPTOGLANDULARES COMPLEJAS: ANTECEDENTES:El tratamiento de las fístulas anales criptoglandulares con inyección de células madre mesenquimales derivadas de tejido adiposo autólogo o alogénico ha mostrado resultados prometedores. Sin embargo, las células madre mesenquimales derivadas de tejido adiposo alogénicas son costosas y el uso de células madre mesenquimales derivadas de tejido adiposo autólogas requiere una liposucción previa y el aislamiento de las células madre, tiempo para el cultivo celular e instalaciones de laboratorio. El tejido adiposo autólogo recién recolectado puede ser una alternativa económica y de fácil acceso.OBJETIVO:Investigar la eficacia de la inyección con tejido adiposo autólogo recién recolectado en fístulas anales criptoglandulares complejas.DISEÑO:Estudio de cohorte prospectivo.ESCENARIO:Centro terciario para el tratamiento de fístulas criptoglandulares en Dinamarca.PACIENTES:Setenta y siete pacientes con fístulas anales criptoglandulares complejas.INTERVENCIONES:Inyecciones de tejido adiposo autólogo recién recolectado. A los pacientes que no lograron la curación después de 8 a 12 semanas se les ofreció una segunda inyección.MEDIDAS DE RESULTADO PRINCIPALES:El resultado primario fue la cicatrización de la fístula definida como ausencia de síntomas de secreción, apertura externa visible e interna palpable mediante examen digital anorrectal en la evaluación clínica 6 meses después del tratamiento final. Los resultados secundarios fueron la combinación clínica y de curación en la resonancia magnética, la reducción de la secreción de la fístula y las molestias anales, y las complicaciones del tratamiento.RESULTADOS:Treinta y nueve pacientes (51%) lograron el resultado primario de curación de la fístula 6 meses después de su tratamiento final. Nueve pacientes (12%) experimentaron una reducción de la secreción y una disminución de las molestias anales. Treinta y siete pacientes (48%) lograron la curación combinada de la fístula clínica y en la resonancia magnética. El tratamiento fue bien tolerado; 5 pacientes (4%) experimentaron eventos adversos graves (infección o sangrado) que requirieron intervención quirúrgica.LIMITACIONES:No se incluyó ningún grupo de control.CONCLUSIÓN:La inyección de tejido adiposo autólogo recién recolectado es un tratamiento seguro de las fístulas anales criptoglandulares complejas y puede ser una alternativa económica de fácil acceso a las células madre mesenquimales derivadas de tejido adiposo autólogo y alogénico cultivadas. Consulte Video Resumen en http://links.lww.com/DCR/Cxx . (Traducción-Dr. Felipe Bellolio ).

[Ulcers in vulva and perineum induced by an anti-anginal drug].

Nicorandil is a type of nicotinamide ester used for the treatment of angina and ischaemic heart disease. A 67-year-old woman was referred to a pelvic floor unit with possible vulvar cancer. She had a painful 2 × 1.5 cm punched-out ulcer. A biopsy showed inflammation, but no evidence of malignancy, infection or dysplasia. She had angina which had been controlled with nicorandil for the past six years. After nearly two years of treatment and examinations nicorandil-induced ulceration was suspected and in liaison with cardiologist, the nicorandil treatment was discontinued. Within a few months, the pain settled, and her ulcers healed.

[Treatment of perianal fistulas with mesenchymal stem cells].

Treatment of perianal fistulas are challenged by insufficient healing and a high rate of relapse. Existing sphincter-sparing procedures have healing rates of around 50%. Treatment with mesenchymal stem cells of both autologous and allogenic origin and freshly collected autologous adipose tissue show both promising healing rates and few complications and may be offered to patients with complicated fistulas not suited for other treatment modalities.

Classifying perianal fistulising Crohn's disease: an expert consensus to guide decision-making in daily practice and clinical trials.

Perianal fistulising Crohn's disease is an aggressive disease phenotype that can have a substantial detrimental impact on patients' quality of life. Current biological understanding of perianal fistulising Crohn's disease remains inadequate and previous classification systems have not provided clear guidance on therapy in clinical practice nor on defining patient cohorts within clinical trials. We propose a new classification system for perianal fistulising Crohn's disease that was developed through a modified nominal group technique expert consensus process. The classification identifies four groups of patients. Key elements include stratification according to disease severity as well as disease outcome; synchronisation of patient and clinician goals in decision making, with a proactive, combined medical and surgical approach, on a treat to patient goal basis; and identification of indications for curative fistula treatment, diverting ostomy, and proctectomy. The new classification retains an element of flexibility, in which patients can cycle through different classes over time. Furthermore, with each specific class comes a paired treatment strategy suggestion and description of clinical trial suitability. The proposed classification system is the first of its kind and is an important step towards tailored standardisation of clinical practice and research in patients with perianal fistulising Crohn's disease.

Molecular differences of adipose-derived mesenchymal stem cells between non-responders and responders in treatment of transphincteric perianal fistulas.

BACKGROUND: Injection of autologous adipose tissue (AT) has recently been demonstrated to be an effective and safe treatment for anal fistulas. AT mesenchymal stem cells (AT-MSCs) mediate the healing process, but the relationship between molecular characteristics of AT-MSCs of the injected AT and fistula healing has not been adequately studied. Thus we aimed to characterize the molecular and functional properties of AT-MSCs isolated from autologous AT injected as a treatment of cryptogenic high transsphincteric perianal fistulas and correlate these findings to the healing process. METHODS: 27 patients (age 45 ± 2 years) diagnosed with perianal fistula were enrolled in the study and treated with autologous AT injected around the anal fistula tract. AT-MSCs were isolated for cellular and molecular analyses. The fistula healing was evaluated by MRI scanning after 6 months of treatment. AT-MSC phenotype was compared between responders and non-responders with respect to fistula healing. RESULTS: 52% of all patients exhibited clinical healing of the fistulas as evaluated 6 months after last injection. Cultured AT-MSCs in the responder group had a lower short-term proliferation rate and higher osteoblast differentiation potential compared to non-responder AT-MSCs. On the other hand, adipocyte differentiation potential of AT-MSCs was higher in non-responder group. Interestingly, AT-MSCs of responders exhibited lower expression of inflammatory and senescence associated genes such as IL1B, NFKB, CDKN2A, TPB3,TGFB1. CONCLUSION: Our data suggest that cellular quality of the injected AT-MSCs including cell proliferation, differentiation capacity and secretion of proinflammatory molecules may provide a possible mechanism underlying fistula healing. Furthermore, these biomarkers may be useful to predict a positive fistula healing outcome. TRIAL REGISTRATION: NTC04834609, Registered 6 April 2021. https://clinicaltrials.gov/ct2/show/NCT04834609.

[Cryptoglandular anal fistulas].

Cryptoglandular anal fistulas (AF) cause recurrent anal abscesses and patients risk multiple surgeries due to low healing rates of sphincter-saving procedures. Knowledge of anal anatomy and imaging with MRI or endoanal sonography is crucial to classify AF as simple or complex depending on risk of anal incontinence after fistulotomy as summarised in this review. Fistulotomy has healing rates of > 90%, risks incontinence, and the procedure is reserved for simple fistulas. Complex AF are treated with a draining seton and then with sphincter-saving procedures which have long-term healing rates of about 50%.

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.

European Society of Coloproctology guidance on the use of mesh in the pelvis in colorectal surgery.

This is a comprehensive and rigorous review of currently available data on the use of mesh in the pelvis in colorectal surgery. This guideline outlines the limitations of available data and the challenges of interpretation, followed by best possible recommendations.

Long-term anorectal function in rectal cancer patients treated with chemoradiotherapy and endorectal brachytherapy.

AIM: The aim was to study anorectal function in long-term survivors after combined, curatively intended, chemoradiotherapy and endorectal brachytherapy for low rectal cancer. METHODS: This was a case-control design. We compared anorectal function by anal manometry, anal functional lumen imaging probe (EndoFLIP) and rectal bag distension in rectal cancer patients (RCPs) and healthy, normal subjects (NSs). Symptoms were assessed by the low anterior resection syndrome (LARS) and Wexner faecal incontinence scores. RESULTS: Thirteen RCPs (12 men, median age 68 years, range 52-92) after 60 Gy radiotherapy, 5 Gy endorectal brachytherapy and oral tegafur-uracil with complete clinical response (median time since treatment 2.8 years, range 2.2-5.6) were compared to 15 NSs (14 men, median age 64 years, range 47-75). RCPs had lower than normal anal resting pressure, 38.6 mmHg (range 8.8-67.7) versus 58.8 mmHg (25.7-105.2) (P < 0.003), and squeeze pressure, 117 mmHg (55.2-203) versus 188 mmHg (103-248) (P < 0.01). Squeeze-induced pressure increase recorded by EndoFLIP was also lower in RCPs (q > 7.56, P < 0.001) as was the anal canal resistance to increasing distension (q = 3.13, P < 0.05). No differences in median rectal volume at first sensation (72 [22-158] vs. 82 [36-190] ml, P = 0.4) or at urge to defaecate (107 [42-227] vs. 132 [59-334] ml, P = 0.2) were found. However, maximum tolerable rectal volume was lower in RCPs (145 [59-319] vs. 222 [106-447] ml, P < 0.02). The median (range) low anterior resection syndrome score was 27 (0-39) for RCPs and 7 (0-23) for NSs (P < 0.001), while the Wexner score was 0 (0-5) versus 0 (0-4) (P = 0.56). CONCLUSION: Radiotherapy combined with endorectal brachytherapy for rectal cancer causes long-term anorectal symptoms, impaired anal sphincter function and reduced rectal capacity.

Effectiveness of infliximab treatment of complex idiopathic anal fistulas.

OBJECTIVES: To investigate the effects of infliximab treatment in patients with complex idiopathic anal fistulas refractory to standard surgical treatment. MATERIALS AND METHODS: We retrospectively evaluated the effects ofinfliximab treatmentin patients with complex idiopathic anal fistulas refractory to standard surgical intervention. The primary outcome was achievement of substantial clinical improvement defined as sustained, reduced inflammatory activity at perioperativeevaluation, i.e., only minimal-to-moderate secretion and induration and a reduction of fistula size of a magnitude that would make it possible to perform a lay-open or sphincter-sparring closure procedure. Secondary outcomes weresymptom improvement, adverse treatment events and fistula healing after the surgical procedure in those achieving the primary outcome. RESULTS: Twenty-two patients were included (18 high transsphincteric, 3complex low transsphincteric, 1 suprasphincteric fistula). Fistulas had been present for a median of 24 [interquartile range, IQR: 12-33] months. In total, 16 patients (73%) achieved the primary outcome of substantial clinical improvement. Median time from infliximab initiation to patients achieved the primary outcome was 11 [IQR: 8-22] months. Sixteen of the patients responding to infliximab received subsequent lay-open or sphincter-sparring closure procedure surgery. Of these, ten (63%) achieved fistula healing. No serious infectious complications to infliximab treatment were seen. One patient developed a new abscess. One patient developed psoriasis (pustolosispalmoplantaris). CONCLUSIONS: Infliximab treatment may be considered a supplement to repeated curettage and setondrainage in the management of selected, complex idiopathic anal fistulas. Such combined treatment may make otherwise refractory fistulas amenable to definitive closure attempts.

Abnormal Neuronal Response to Rectal and Anal Stimuli in Patients Treated for Distal Rectal Cancer With High-Dose Chemoradiotherapy Followed By Watchful Waiting.

BACKGROUND: Watchful waiting in patients with rectal cancer with complete clinical response after chemoradiation therapy has gained increased popularity to avoid morbidity and mortality associated with surgery. Irradiation of the pelvis causes bowel dysfunction, but the effect on anorectal sensory function remains obscure in this patient category. OBJECTIVE: The aim of this study was to characterize the sensory pathways of the gut-brain axis in patients with rectal cancer treated solely with chemoradiation therapy (nonconventional regime/dose) compared with healthy volunteers. DESIGN: This is an explorative study. SETTINGS: Sensory evaluation by rectal distension was performed and cortical evoked potentials were recorded during rapid balloon distensions of the rectum and anal canal. Latencies and amplitudes of cortical evoked potentials were compared, and the relative amplitude of 5 spectral bands from recorded cortical evoked potentials was used as an additional proxy of neuronal processing. PATIENTS: Patients with rectal cancer solely with chemoradiation therapy (n = 13) a median of 3.2 years ago (range, 2.3-5.6 y) and healthy volunteers (n = 13) were included. MAIN OUTCOME MEASURES: Cortical evoked potentials were measured. RESULTS: Patients had 35% lower rectal capacity at a maximum tolerable volume (p = 0.007). We found no differences in rectal cortical evoked potential latencies (p = 0.09) and amplitudes (p = 0.38) between groups. However, spectral analysis of rectal cortical evoked potentials showed a decrease in θ (4-8 Hz) and an increase in ß (12-32 Hz) band activity in patients (all p < 0.001). Anal cortical potentials showed an increase in α (8-12 Hz) and ß and a decrease in γ (32-70 Hz) band activity (all p < 0.001) in patients compared with healthy volunteers. LIMITATIONS: This is an explorative study of limited size. CONCLUSIONS: Chemoradiation therapy for distal rectal cancer causes abnormal cortical processing of both anal and rectal sensory input. Such central changes may play a role in symptomatic patients, especially when refractory to local treatments. See Video Abstract at http://links.lww.com/DCR/B270. RESPUESTA NEURONAL ANORMAL A ESTÍMULOS RECTALES Y ANALES, EN PACIENTES TRATADOS POR CÁNCER RECTAL DISTAL, CON QUIMIORRADIOTERAPIA DE DOSIS ALTA, SEGUIDA DE ESPERA VIGILANTE: La espera vigilante en pacientes de cáncer rectal, con respuesta clínica completa después de la quimiorradiación, ha ganado una mayor popularidad en evitar la morbilidad y mortalidad asociadas con la cirugía. La irradiación de la pelvis causa disfunción intestinal, pero el efecto sobre la función sensorial ano-rectal sigue siendo no claro, en esta categoría de pacientes.El objetivo de este estudio, fue caracterizar las vías sensoriales del eje intestino-cerebro en pacientes con cáncer rectal, tratados únicamente con quimiorradiación (régimen / dosis no convencional), en comparación con voluntarios sanos.Es un estudio exploratorio.Se realizó una evaluación sensorial por distensión rectal y se registraron los potenciales evocados corticales, durante las distensiones rápidas con balón en recto y canal anal. Se compararon las latencias y amplitudes de los potenciales evocados corticales, y la amplitud relativa de cinco bandas espectrales registradas, de potenciales evocados corticales, se usaron como proxy adicional del procesamiento neuronal.Pacientes de cáncer rectal, únicamente con terapia de quimiorradiación (n = 13) mediana de 3.2 años (rango 2.3-5.6) y voluntarios sanos (n = 13).Potenciales evocados corticales.Pacientes tuvieron una capacidad rectal menor del 35%, al volumen máximo tolerable (p = 0.007). No encontramos diferencias en las latencias potenciales evocadas corticales rectales (p = 0.09) y amplitudes (p = 0.38) entre los grupos. Sin embargo, el análisis espectral de los potenciales evocados corticales rectales, mostró una disminución en theta (4-8 Hz) aumento en beta (12-32 Hz), y actividad en banda en pacientes (todos p <0.001). Los potenciales evocados corticales anales mostraron un aumento en alfa (8-12 Hz) y beta, disminución en gamma (32-70 Hz), y actividad en banda (todos p <0.001), en pacientes comparados a voluntarios sanos.Este es un estudio exploratorio de tamaño limitado.La quimiorradiación para el cáncer rectal distal, ocasiona procesos corticales sensoriales anormales anales y rectales. Tales cambios centrales pueden desempeñar un papel en pacientes sintomáticos, especialmente cuando son refractarios a tratamientos locales. Consulte Video Resumen en http://links.lww.com/DCR/B270.

Sacral Nerve Modulation Has No Effect on the Postprandial Response in Irritable Bowel Syndrome.

PURPOSE: Irritable bowel syndrome is a common gastrointestinal disorder with a global prevalence of approximately 11%. Onset or worsening of symptoms following digestion is one of the characteristics of the condition. The present study aimed at evaluating the postprandial sensory and motor response before and after treatment with sacral nerve modulation. PATIENTS AND METHODS: Twenty-one irritable bowel syndrome patients, 12 diarrhea-predominant and 9 mixed, were eligible for a 6-week sacral nerve modulation test period. Patients were investigated with multimodal impedance planimetry including a standardized meal at baseline and at the end of 2 weeks of suprasensory stimulation embedded in the 6-week sacral nerve modulation period. RESULTS: There was no statistical significant difference in the sensory response to heat or cold before and after sacral nerve modulation, p>0.05. At baseline, wall tension increased after the meal (mean 124.79 [range 82.5 to 237.3] mmHg.mm before the meal, mean 207.76 [range, 143.5 to 429] mmHg.mm after the meal), p=0.048 indicating a postprandial response. During sacral nerve modulation, the postprandial increase in wall tension did not reach statistical significance (mean 86.79 [range 28.8 to 204.5] mmHg.mm before the meal, mean 159.71 [range 71.3 to 270.8] mmHg.mm after the meal), p=0.277. However, there was no statistically significant difference between the postprandial wall tension at baseline and during sacral nerve modulation, p=0.489. Likewise, we found no difference between pressure or stretch ratio at baseline and during sacral nerve modulation, p>0.05. CONCLUSION: Sacral nerve modulation does not exert its positive treatments effects in diarrhea-predominant and mixed irritable bowel syndrome through a modulation of the postprandial response.

Functional Outcome after Laparoscopic Posterior Sutured Rectopexy Versus Ventral Mesh Rectopexy for Rectal Prolapse: Six-year Follow-up of a Double-blind, Randomized Single-center Study.

BACKGROUND: Laparoscopic ventral mesh rectopexy (LVMR) for rectal prolapse has been implemented to reduce postoperative bowel symptoms. The preoperative-to-postoperative change in a double-blinded, randomized study comparing it to laparoscopic posterior sutured rectopexy (LPSR) found no significant difference between the two procedures after one year. The aim of this study was to investigate the long-term functional outcomes. METHODS: From November 2006-January 2014, 75 patients were randomized to LVMR (n = 37) or LPSR (n = 38). In March 2017, questionnaires containing constipation symptom score (PAC-SYM), quality of life score (PAC-QoL), obstructed defecation score (ODS), Cleveland clinic constipation and incontinence scores (CCCS, CCIS) were mailed to all the patients included in the RCT. Prolapse recurrences and mesh complications were recorded. FINDING: Sixty-nine patients were available for long-term follow-up. Questionnaires were completed by 64 patients (94.4%). The median follow-up was 6.1 years. The total PAC-QoL was significantly lower in the LVMR group 0.26 (0.14-0.83) compared to the LPSR group 0.93(0.32-1.61)(P = 0.008). The total PAC-SYM was significantly lower in the LVMR group 0.5 (0.21-0.87) compared to the LPSR group 1.0 (0.5-1.5)(P = 0.031). Except for CCIS, the ODS and the CCCS significantly favored the LVMR group at six years (P = 0.011 & 0.017). Only three(8.82%) patients in the LVMR group developed recurrence compared to seven(23.33%) in the LPSR group (P = 0.111). INTERPRETATION: The long-term functional outcome after LVMR is superior to that after LPSR. Larger multicenter studies are warranted. FUNDING: None.

Sacral nerve modulation for irritable bowel syndrome: A randomized, double-blinded, placebo-controlled crossover study.

BACKGROUND: Irritable bowel syndrome (IBS) is among the most common gastrointestinal disorders, and a substantial proportion of patients have an insufficient response to treatment. In a single-blinded study, sacral nerve modulation (SNM) significantly reduced symptoms of IBS. The aim of the present double-blinded, randomized, placebo-controlled study was to evaluate the effect of SNM for IBS. METHODS: We included patients with diarrhea-predominant or mixed IBS and a minimum baseline IBS-specific symptom score of 40 points (Gastrointestinal Symptom Rating Scale-IBS version). Patients underwent a 6-week period of SNM. In the first 4 weeks, the patients were randomized 1:1 to have the neurostimulator set subsensory or OFF for 2 weeks and then the opposite for another 2 weeks. Patients and investigators were blinded to settings. In the remaining 2 weeks, the stimulation was set suprasensory. IBS-specific symptoms and quality of life were assessed with validated questionnaires and bowel diaries. KEY RESULTS: Twenty-one patients were randomized and eligible for analysis. The IBS-specific symptom score was reduced with borderline significance during stimulation (subsensory-OFF median change -1 (-26, 9), OFF-subsensory median change 8 (-11, 36); P = 0.0572). Pain was significantly reduced during stimulation (subsensory-OFF median change -1.5 (-4, 1), OFF-subsensory median change 1 (-4, 3); P = 0.0188), along with the number of daily bowel movements (subsensory-OFF median change 0 (-1.8, 0.2), OFF-subsensory median change 0.2 (-0.5, 1.1); P = 0.0373). The median placebo effect was 14% (0, 55). CONCLUSION AND INFERENCES: Sacral nerve modulation for IBS seems promising but should be considered experimental until larger multicenter studies have been performed.

Efficacy of Injection of Freshly Collected Autologous Adipose Tissue Into Perianal Fistulas in Patients With Crohn's Disease.

BACKGROUND & AIMS: Perianal fistulas are common in patients with Crohn's disease (CD). Injections of cultured autologous and allogeneic adipose tissue-derived stem cells have been shown to heal CD-associated fistulas. Unfortunately, this treatment is time consuming and expensive. We investigated the effects of injecting freshly collected autologous adipose tissue into perianal fistulas in patients with CD. METHODS: In a prospective interventional study, freshly collected autologous adipose tissues were injected into complex perianal fistulas of 21 patients with CD, from March 2015 through June 2018. The primary endpoint was complete fistula healing (no symptoms of discharge, no visible external fistula opening in the perineum, and no internal opening detected by rectal digital examination) 6 months after the last injection. We performed pelvic magnetic resonance imaging to confirm fistula resolution in patients with intersphincter and transsphincter fistulas who showed complete healing at clinical examination. Patients without complete fistula healing after 6 weeks and those with later relapse were offered additional injections. No control individuals were included. RESULTS: Six months after the last adipose tissue injection, 12 patients (57%) had complete fistula healing. Three patients (14%) had ceased fistula secretion, and 1 patient (5%) reported reduced secretion. Among 10 patients with trans-sphincter or inter-sphincter fistulas, magnetic resonance imaging showed complete fistula resolution in 9 patients and a markedly reduced gracile fistula in the remaining patient. Of the 12 patients with complete fistula healing, 9 (43%) required 1 injection, 2 (10%) required 2 injections, and 1 (5%) required 3 injections. The predominant adverse effect was postprocedure proctalgia lasting a few days. Two patients developed small abscesses, 1 had urinary retention, and 1 had minor bleeding during liposuction. CONCLUSION: In a study of 21 patients with CD and perianal fistulas, we found injection of recently collected autologous adipose tissue to be safe and to result in complete fistula healing in 57% of patients. ClinicalTrials.gov, Number: NCT03803917.

Abnormal neuronal response to rectal and anal stimuli in patients treated with primary radiotherapy for anal cancer.

INTRODUCTION: Sphincter-sparing radiotherapy or chemoradiation (RT/CRT) have become the standard treatments for most patients with anal cancer. Unfortunately, long-term survivors often suffer from severe bowel symptoms indicating sensory dysfunction. The aim of the present study was to characterize the sensory pathways of the brain-gut axis after radiotherapy for anal cancer. METHOD: Cortical evoked potentials (CEPs) were recorded during repeated, rapid balloon distensions of the rectum and anal canal in 13 patients with anal cancer treated with radiotherapy or chemoradiation and in 17 healthy volunteers. Latencies and amplitudes of rectal CEPs were compared between the groups. CEPs from both rectal and anal distensions were examined using single sweep spectral band analysis to determine the relative amplitude of five spectral bands as a proxy of neuronal processing. RESULTS: Groups were comparable by age (62.4 ±â€¯7.8 vs 58.9 ±â€¯8.9, p < 0.32) and gender. Patients had a mean Wexner fecal incontinence score of 5.5 (±3.8) and median LARS Score of 29 (0-39). Rectal CEP latencies were prolonged in patients (F = 11.7; p < 0.001), whereas amplitudes were similar (F = 0.003; p = 0.96). Spectral analysis of CEPs from rectal distensions showed significant differences between groups in theta (4-8 Hz), alpha (8-12 Hz), beta (12-32 Hz) and gamma (32-70 Hz) bands (all p < 0.001) and CEPs from anal distensions showed significant differences in the alpha, beta and gamma bands (all p ≤ 0.002). CONCLUSION: Patients treated with RT/CRT for anal cancer have impaired ano-rectal sensory pathways and abnormal cortical processing. This may play a central role for the pathogenesis of late proctopathy.

Ultrasound-Guided Pudendal Nerve Block at the Entrance of the Pudendal (Alcock) Canal: Description of Anatomy and Clinical Technique.

BACKGROUND AND OBJECTIVES: Ultrasound-guided techniques for pudendal nerve block have been described at the level of the ischial spine and transperineally. Theoretically, however, blockade of the pudendal nerve inside Alcock canal with a small local anesthetic volume would minimize the risk of sacral plexus blockade and would anesthetize all 3 branches of the pudendal nerve before they ramify in the ischioanal fossa. This technical report describes a new ultrasound-guided technique to block the pudendal nerve. The technique indicates an easy and effective roadmap to target the pudendal nerve inside the Alcock canal by following the margin of the hip bone sonographically along the greater sciatic notch, the ischial spine, and the lesser sciatic notch. METHODS: The technique was applied bilaterally in 3 patients with chronic perineal pain. The technique described was also used to locate the pudendal nerve within Alcock canal and inject dye bilaterally in 2 cadavers. RESULTS: Complete pinprick anesthesia was obtained in the pudendal territory of the perineum in all 3 patients. Pain was effectively alleviated or reduced in all patients with no affection of the sacral plexus nerve branches. In the 2 cadavers, all 4 pudendal nerves were successfully targeted and colored. CONCLUSIONS: This new technique is based on easily recognizable sonoanatomical patterns. It probably implies no risk of sacral plexus blockade, and the pudendal nerve is anesthetized before any branches ramify from the main trunk. This promising new technique must be validated in future clinical trials.

Management of patients with faecal incontinence.

Faecal incontinence, defined as the involuntary loss of solid or liquid stool, is a common problem affecting 0.8-8.3% of the adult population. Individuals suffering from faecal incontinence often live a restricted life with reduced quality of life. The present paper is a clinically oriented review of the pathophysiology, evaluation and treatment of faecal incontinence. First-line therapy should be conservative and usually include dietary adjustments, fibre supplement, constipating agents or mini enemas. Biofeedback therapy to improve external anal sphincter function can be offered but the evidence for long-term effect is poor. There is good evidence that colonic irrigation can reduce symptoms and improve quality of life, especially in patients with neurogenic faecal incontinence. Surgical interventions should only be considered if conservative measures fail. Sacral nerve stimulation is a minimally invasive procedure with high rate of success. Advanced surgical procedures should be restricted to highly selected patients and only performed at specialist centres. A stoma should be considered if other treatment modalities fail.