Perianal fistulizing Crohn's disease-associated anorectal and fistula cancers: systematic review and expert consensus.

BACKGROUND AND AIMS: Perianal fistulizing Crohn's disease (PFCD)-associated anorectal and fistula cancers are rare but often devastating diagnoses. However, given the low incidence and consequent lack of data and clinical trials in the field, there is little to no guidance on screening and management of these cancers. To inform clinical practice, we developed consensus guidelines on PFCD-associated anorectal and fistula cancers by multidisciplinary experts from the international TOpClass consortium. METHODS: We conducted a systematic review by standard methodology, using the Newcastle-Ottawa Scale quality assessment tool. We subsequently developed consensus statements using a Delphi consensus approach. RESULTS: Of 561 articles identified, 110 were eligible, and 76 articles were included. The overall quality of evidence was low. The TOpClass consortium reached consensus on six structured statements addressing screening, risk assessment, and management of PFCD-associated anorectal and fistula cancers. Patients with longstanding (>10 years) PFCD should be considered at small but increased risk of developing perianal cancer, including squamous cell carcinoma of the anus(SCCA) and anorectal carcinoma. Risk factors for SCCA, notably human papilloma virus (HPV), should be considered. New, refractory, or progressive perianal symptoms should prompt evaluation for fistula cancer. There was no consensus on timing or frequency of screening in patients with asymptomatic perianal fistula. Multiple modalities may be required for diagnosis, including an exam under anesthesia (EUA) with biopsy. Multidisciplinary team efforts were deemed central to the management of fistula cancers. CONCLUSION: Inflammatory bowel disease (IBD) clinicians should be aware of the risk of PFCD-associated anorectal and fistula cancers in all patients with PFCD. The TOpClass consortium consensus statements outlined herein offer guidance in managing this challenging scenario.

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 ).

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.

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.

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.

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.

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 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 stimulation for faecal incontinence - efficacy confirmed from a two-centre prospectively maintained database.

INTRODUCTION: Sacral nerve stimulation (SNS) has been recognised as an effective treatment for faecal incontinence. Many unresolved questions could be answered when comparing large data-series from different centres providing prospective data. AIM: To present data, from an international two-centre SNS prospective database (SNSPD) on functional outcome and management of surgical complications in patients treated with SNS for faecal incontinence. METHOD: The SNSPD was designed in order to gather detailed pre- and perioperative information followed by a close follow-up in all patients undergoing SNS for bowel dysfunction. The SNSPD was open for inclusion of newly SNS implanted patients in May 2009, and closed on 31 December 2013. Two-centres Aarhus, Denmark, and Nantes, France, included and monitored all patients implanted due to bowel dysfunction according to database criteria. RESULTS: In total, 164 faecal incontinent patients with a median follow-up of 22 (range 1-50) months were implanted. The Wexner incontinence score improved from 15 (range, 3-20) at baseline to 9 (range, 0-20) at latest follow-up (P < 0.001) and VAS impact on daily life improved from 85.5 (range, 3-100) to 20 (range, 0-100) (P < 0.001). Additional surgical intervention was required in 19.5 % during follow-up. Repositioning of the pacemaker due to pain or migration was the most common complication in 12.1 %. Infections leading to explantation occurred in 3.0 %.

Outcome of sacral nerve stimulation for fecal incontinence at 5 years.

OBJECTIVE: This study aimed to evaluate the outcome of sacral nerve stimulation (SNS) for fecal incontinence at 5 years after implantation and to identify predictors of sustained efficacy. BACKGROUND: There is a lack of knowledge about the long-term outcome of SNS for fecal incontinence. METHODS: Prospectively collected data from patients who underwent implantation of an SNS device between 2001 and 2006 were reviewed. RESULTS: One hundred and one patients were available for outcome evaluation at 5 years. Sixty of 101 patients [42.6% on intention-to-treat (ITT) and 55.6% per protocol (PP)] reported a favorable outcome, 41 patients (ITT 29.1%; PP 38.0%) reported an unfavorable outcome, of whom 24 patients (ITT 17.0%; PP 22.2%) had their device explanted or permanently switched off before 5 years. Wexner incontinence scores improved significantly from a baseline median of 16 (range 6-20) to a median of 6 (range 0-20) at 3 months (P < 0.0001), and the improvement compared with baseline was maintained throughout the 5-year follow-ups (P < 0.0001).Age was a negative predictive factor [odds ratio (OR): 0.96 each year increase, 95% confidence interval (CI): 0.92-0.99; P = 0.016]. Positive predictors included improvement of urge incontinence episodes during percutaneous nerve evaluation (OR: 10.8; 95% CI: 1.72-132; P = 0.036), improvement of incontinence scores at 6 months from baseline (OR: 6.29; 95% CI: 1.33-34.3; P = 0.025), particularly improvement of incontinence scores from 3 to 6 months (OR: 41.5; 95% CI: 3.51-811; P = 0.007). Overall, 521 reportable events were recorded from 94 patients (93.1%). CONCLUSIONS: On an ITT analysis, 42.6% of patients reported favorable outcomes at 60 months. Patient's age, improvement of urge incontinence during PNE, and sustained efficacy during the first 6 months after implantation are some of the predictors identified.

A randomized, controlled, crossover study of sacral nerve stimulation for irritable bowel syndrome.

OBJECTIVE: To investigate whether sacral nerve stimulation reduces irritable bowel syndrome (IBS)-specific symptoms by a randomized, controlled, crossover study. BACKGROUND: IBS affects 3% to 22% of the population worldwide, but most patients continue to have symptoms despite treatment. METHODS: Patients included from our tertiary center had diarrhea-predominant or mixed IBS, with a minimum baseline IBS symptom score (Gastrointestinal Syndrome Rating Scale-IBS questionnaire) of 40 points reduced by a minimum of 30% during the percutaneous nerve evaluation before permanent implantation. Patients were randomized (1:1) to have the stimulator ON or OFF for 1 month and then the opposite for another month. Investigators and patients were not informed of the setting. IBS-specific symptoms and quality of life were assessed through bowel diaries and validated questionnaires. Primary endpoint was the IBS-specific symptom score. RESULTS: Twenty-one patients were randomized. Ten were eligible for analysis in each group. IBS-specific symptom scores were significantly reduced during stimulation: the median difference in the ON-OFF group was 12 (range, -22 to 44) and in the OFF-ON group -17.5 (range, -48 to -1) (P = 0.0009). IBS-specific quality-of-life scores improved significantly during stimulation: the median difference in the ON-OFF group was 16 (range, -24 to 69) and in the OFF-ON group -42.5 (range, -77 to 0) (P = 0.0003). At 1-year follow-up, the median IBS-specific symptom score (25; range, 13-65) was significantly lower than that at baseline (62; range, 45-80) (P = 0.0001). CONCLUSIONS: Sacral nerve stimulation significantly reduces symptoms and improves quality of life of highly selected patients with IBS.

A randomised, controlled study of small intestinal motility in patients treated with sacral nerve stimulation for irritable bowel syndrome.

BACKGROUND: Irritable bowel syndrome (IBS) is among the most common gastrointestinal disorders worldwide. In selected patients with severe diarrhoea-predominant or mixed IBS subtypes sacral nerve stimulation (SNS) alleviates IBS-specific symptoms and improves quality of life. The mode of action, however, remains unknown. The present study aimed to evaluate the effect of SNS on small intestinal motility in IBS patients. METHODS: Twenty patients treated with SNS for severe diarrhoea-predominant or mixed IBS were included in a randomised, controlled, crossover study. The neurostimulator was turned ON or OFF for the first one month and then to the opposite setting for the next month. Gastrointestinal transit patterns were investigated with the Motility Tracking System-1 (MTS-1) at the end of each the ON and OFF period. Primary endpoint was change in the velocity of the magnetic pill within the small intestine. Statistical testing was performed with Wilcoxon's rank sum test and Fisher's exact test. RESULTS: The median velocity of the magnetic pill through the small intestine in the fasting state was not significantly different between periods with and without SNS (Group ON-OFF: median change 0 m/h (range -1.07, 0.63), Group OFF-ON: median change 0.27 m/h (range -0.59, 1.12)) (p = 0.25). Neither, was the median velocity of the magnetic pill through the small intestine in the postprandial state significantly different between periods with and without SNS (Group ON-OFF: median change -0.13 m/h (range -0.46, 0.23), Group OFF-ON: median change 0.015 m/h (range -0.48, 0.59)) (p = 0.14). CONCLUSION: Even though SNS may reduce symptoms of diarrhoea-predominant and mixed IBS, it has no detectable effect on small intestinal transit patterns. TRIAL REGISTRATION: Clinical.trials.gov, (NCT00919672).

Pathophysiology of late anorectal dysfunction following external beam radiotherapy for prostate cancer.

BACKGROUND: Patients treated with external beam radiotherapy (EBRT) may suffer from long-term anorectal adverse effects. The purpose of the present study was to assess long-term functional and structural anorectal changes in patients previously treated with EBRT for prostate cancer and to suggest the mechanism behind the development of the adverse effects. MATERIAL AND METHODS: Our previously proposed RT-induced anorectal dysfunction (RT-ARD) score, developed with the intention to survey anorectal dysfunction was used to identify patients with and without anorectal symptoms. Among 309 patients surveyed with the questionnaire, we chose 23 patients with the highest RT-ARD score and 19 patients with the lowest RT-ARD score. They were investigated by multimodal rectal sensory stimulation, standard anal physiological tests. Changes of the rectal mucosa were assessed by flexible sigmoidoscopy and graded by the Vienna Rectoscopy Score (VRS). RESULTS: The mean follow-up time was 3.8 (range, 2.8; 8.6) years in patients with high RT-ARD and 3.8 (range, 2.6; 5.9) in patients with low RT-ARD. Endoscopic evaluation revealed higher VRS scores in patients with high RT-ARD compared to patients with low RT-ARD (p = 0.002). Patients with high RT-ARD had increased rectal sensory response to distension manifested both as volume (p = 0.006) and cross-sectional area (p = 0.04), and they had reduced maximum anal resting pressure assessed by anal manometri (p = 0.02). CONCLUSIONS: Long-term anorectal symptoms correlate to changes in anorectal biomechanical properties and rectal mucosal injury. Our data suggests that RT-induced long-term anorectal dysfunction is multifactorial caused by injury of the rectal mucosa and the internal anal sphincter combined with increased rectal sensitivity and reduced rectal functional capacity.

Baseline factors predictive of patient satisfaction with sacral neuromodulation for idiopathic fecal incontinence.

PURPOSE: Sacral neuromodulation (SNM) is an established treatment for fecal incontinence (FI). A recent study from our group found that the relationship between patient satisfaction and clinical outcome is complex and does not match the traditional used success criteria. Therefore, the ability to predict patient satisfaction must be given priority. The aim of the present study is to identify baseline factors predictive of patient satisfaction, with SNM, for idiopathic FI. METHODS: We analyzed data from patients treated with SNM for idiopathic FI in Aarhus, Denmark, and Maastricht, The Netherlands. A questionnaire considering self-reported satisfaction was mailed to these patients and compared to baseline characteristics. Logistic regression was used to determine the predictive value of baseline demographic and diagnostic variables. RESULTS: In total, 131 patients were included in the analysis. Patient satisfaction with the current treatment result was reported in 75 patients. Fifty-six patients were dissatisfied with SNM treatment, after median 46 months (range 11-122) with permanent implantation. Pudendal nerve terminal motor latency (PNTML) was the solely identified predictor for long-term patient satisfaction. A subgroup univariate-logistic regression analysis showed that PNTML ≤ 2.3 ms at the side of lead implantation was a statistically significant predictor for patient satisfaction (odds ratio (OR) 2.3, 95% confidence interval (CI) 1.01-5.24, p = 0.048). CONCLUSION: Baseline PNTML measurement may be predictive of long-term satisfaction with SNM therapy for idiopathic FI. Further studies are needed to confirm this result.

Sacral nerve stimulation at subsensory threshold does not compromise treatment efficacy: results from a randomized, blinded crossover study.

BACKGROUND AND OBJECTIVE: : Stimulation amplitude used in sacral nerve stimulation (SNS) is at or just above the sensory threshold (ST). This randomized, blinded crossover study aimed to document if stimulation at 75% or 50% of the ST would be as effective as stimulation at the ST for fecal incontinence (FI). METHOD: : FI patients treated with SNS, who were satisfied with current treatment results and had a minimum symptom reduction of 75%, were eligible. Patients were randomized into 3 periods of 4-week stimulation: ST, 75% of the ST, and 50% of the ST. Patients completed a bowel habit diary and questionnaires on bowel functions and patient satisfaction at the study baseline and in each study period. RESULTS: : Nineteen patients (18 females) with a mean follow-up of 51.7 ± 29.9 months were included from January to April 2010. The mean FI episodes per 3 weeks decreased from pre-SNS therapy 33.6 ± 31.6 to 1.1 ± 2.2 at the study baseline (P < 0.001). Decreasing the stimulation amplitude to as low as 50% of the ST did not affect the overall number of incontinent episodes (P = 0.078). The Wexner incontinence score dropped from 16.5 ± 2.5 for pre-SNS therapy to 7.4 ± 3.1 at the study baseline (P < 0.001). Decreasing the stimulation amplitude to ST, 75% of the ST or 50% of the ST, did not change the Wexner score when compared with the study baseline (P = 0.581). In general, patient satisfaction was high at the study baseline and did not deteriorate as the stimulation amplitude was decreased to 50% of the ST (P = 0.932). CONCLUSIONS: : Subsensory stimulation as low as 50% of the ST is as effective as stimulation at or above the ST. The study was approved by the Regional Committee on Biomedical Research Ethics, Denmark, and registered at ClinicalTrials.gov (NCT01130870).

[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.