What are the outcomes in patients referred to a tertiary referral centre for Crohn's rectovaginal fistula surgery?

AIM: Rectovaginal fistulas in patients with Crohn's disease are challenging to manage, and surgical treatment remains the best option for achieving permanent closure of the fistula. Biologicals are now used routinely for patients with Crohn's disease. The aim of this study was to investigate the surgical procedures used by us to treat rectovaginal fistula in patients with Crohn's disease in the era of biologicals. METHOD: Patients with Crohn's disease who underwent surgery for a rectovaginal fistula between 2010 and 2020 were included in this retrospective study and were identified from a prospectively maintained institutional database. Collected variables included demographics, perioperative and operative variables and data regarding medications used. Success of the procedure was defined as no symptoms at least 6 months after definitive repair and/or stoma closure. RESULTS: Twenty patients (out of 80 referred for evaluation) underwent surgery with intent to close the fistula and had at least 6 months of follow-up. Mean age was 44 ± 12 years with a median follow-up duration of 33 months (range 6-130 months). Forty per cent of the patients had a history of at least two surgeries to close the fistula. The overall healing rate was 70% (14/20). The most performed procedure was a transanal rectal advancement flap (7/20), with a success rate of 85%. CONCLUSION: Rectovaginal fistula in Crohn's disease is difficult to cure; according to our results almost half of these patients have multiple surgeries due to recurrence. Multiple procedures may be offered for this challenging problem in motivated patients. Perioperative diversion should be strongly considered.

ACG Clinical Guidelines: Management of Benign Anorectal Disorders.

Benign anorectal disorders of structure and function are common in clinical practice. These guidelines summarize the preferred approach to the evaluation and management of defecation disorders, proctalgia syndromes, hemorrhoids, anal fissures, and fecal incontinence in adults and represent the official practice recommendations of the American College of Gastroenterology. The scientific evidence for these guidelines was assessed using the Grading of Recommendations Assessment, Development and Evaluation process. When the evidence was not appropriate for Grading of Recommendations Assessment, Development and Evaluation, we used expert consensus to develop key concept statements. These guidelines should be considered as preferred but are not the only approaches to these conditions.

Does the Length of the Prolapsed Rectum Impact Outcome of Surgical Repair?

BACKGROUND: There are many surgical options for the treatment of rectal prolapse with varying recurrence rates reported. The association between rectal prolapse length and recurrence risk has not been explored previously. OBJECTIVE: The purpose of this study was to determine whether length of prolapse predicts a risk of recurrence. DESIGN: Consecutive patients from a prospectively collected institutional review board-approved data registry were evaluated. SETTINGS: The study was conducted at the Cleveland Clinic Department of Colorectal Surgery. PATIENTS: All patients from 2010 to 2018 who underwent surgical intervention for rectal prolapse were included. INTERVENTION: Perineal repair with Delorme procedure and Altemeier, as well as abdominal repair with ventral rectopexy, resection rectopexy, and posterior rectopexy, was included. MAIN OUTCOME MEASURES: Prolapse length, recurrence, type of surgery, and primary or secondary procedure were measured. RESULTS: In total, 280 patients had prolapse surgery over 8 years, mean age was 59 years (SD = 18 y), and 92.4% were female. Seventy percent had a prolapse length documented as <5 cm, and 30% had prolapse length documented as >5 cm. The mean prolapse length was 4.8 cm (SD = 2.9 cm). The overall rate of recurrent prolapse was 18%. There were 51 patients who had a recurrent prolapse after their first prolapse surgery. Factors significant for recurrence on univariate analysis were a perineal approach (p = 0.03), previous Delorme procedure (p < 0.001), and prolapse length >5 cm (p = 0.04). On multivariate analysis there was significantly increased recurrence with length of prolapse >5 cm (OR = 2.2 (95% CI, 1.1-4.4); p = 0.02) and having a previous Delorme procedure (OR = 4.0 (95% CI, 1.6-10.1); p = 0.004). For each 1-cm increase in prolapse, the odds of recurrence increased by a factor of 2.2. LIMITATIONS: This was a retrospective study of a heterogenous patient cohort. CONCLUSIONS: The greater the length of prolapsed rectum, the greater the risk of recurrence. The length of prolapse should be considered when planning the most appropriate surgical repair to modify the recurrence risk. See Video Abstract at http://links.lww.com/DCR/B463. EL TAMAÑO DEL RECTO PROLAPSADO AFECTA EL RESULTADO DE LA REPARACIÓN QUIRÚRGICA?: Existen muchas opciones quirúrgicas para el tratamiento del prolapso de recto con diferentes tasas de recurrencia publicadas. La asociación entre el tamaño del prolapso rectal y el riesgo de recurrencia no se han explorado previamente.Determinar si el largo en el tamaño del prolapso predice un riesgo de recidiva.Se evaluaron pacientes consecutivos de un registro de datos aprobado por el IRB recopilado prospectivamente.Departamento de cirugía colorrectal de la Clínica Cleveland, en Ohio.Todos aquellos pacientes que entre 2010 y 2018 se sometieron a una intervención quirúrgica por prolapso completo de recto.La reparación perineal incluyó los procedimientos de Altemeier y Delorme. Las reparaciones abdominales incluidas fueron la rectopexia ventral, la rectopexia con resección y la rectopexia posterior.Tamaño del prolapso, recurrencia, tipo de intervención quirúrgica y tipo de procedimiento (primario o secundario).En total, 280 pacientes se sometieron a cirugía de prolapso rectal durante 8 años, la edad media fue de 59 años (DE 18) donde el 92,4% eran mujeres. El 70% tenían un tamaño de prolapso documentado como < 5 cm y 30% tenían un tamaño de prolapso documentada como > 5 cm. La longitud media del prolapso fue de 4,8 cm (DE 2,9).La tasa general de recidiva del prolapso fue de 18%. Hubo 51 pacientes que presentaron recidiva del prolapso después de una primera cirugía. Los factores significativos para la recidiva en el análisis univariado fueron el abordaje perineal (p = 0.03), un procedimiento de Delorme previo (p <0.001) y el tamaño del prolapso > 5 cm (p = 0.04). En el análisis multivariado, hubo un aumento significativo de la recidiva en aquellos prolapsos de > 5 cm (OR 2,2; IC del 95%: 1,09-4,4; p = 0,02) con un procedimiento de Delorme previo (OR 4; IC del 95%: 1,6 a 10,1; p = 0,004). Por cada centímetro de tamaño del prolapso, las probabilidades de recidiva aumentaron en un factor de 2,2.Estudio retrospectivo de una cohorte de pacientes heterogénea.Cuanto mayor es el tamaño del recto prolapsado, mayor es el riesgo de recidiva. Se debe evaluar muy cuidadosamente el tamaño de los prolapsos para escoger la corrección quirúrgica más apropiada y así disminuir el riesgo de recidivas.Consulte Video Resumen en http://links.lww.com/DCR/B463. (Traducción-Dr Xavier Delgadillo).

Reducing Patient Burden and Improving Data Quality With the New Cleveland Clinic Colorectal Cancer Quality of Life Questionnaire.

BACKGROUND: The Cleveland Clinic Colorectal Cancer Quality of Life Questionnaire was developed in response to the need for a new, fast, and comprehensive tool for evaluating quality of life in patients who have colorectal cancer. Available surveys such as the SF-12, SF-36, Functional Assessment of Cancer Therapy-Colorectal, and European Organization for Research and Treatment of Cancer are either too general to be informative or too lengthy to complete. OBJECTIVE: The aim was to validate the Cleveland Clinic Foundation Colorectal Quality of Life Questionnaire. DESIGN: Data were obtained as part of a prospective randomized controlled trial. SETTINGS: This was a worldwide multicenter study with 2 domestic and 5 international locations. PATIENTS: This study randomly assigned 190 patients between the ages of 18 and 80 undergoing surgery for low rectal cancer. Of those randomly assigned, 142 with partially complete surveys were analyzed for selection bias and acceptability, and 95 with complete surveys were analyzed for survey validity. INTERVENTIONS: Patients received either a J-pouch, side-to-end anastomosis, or straight anastomosis. MAIN OUTCOME MEASURE: The study evaluated survey validity measures such as standardized Cronbach α for internal consistency and Spearman correlation coefficients for construct validity, convergent validity, and responsiveness. Univariate analyses were used to assess discriminative validity. RESULTS: Sufficient acceptability, construct, and convergent validity and responsiveness were achieved. All scores showed great internal consistency (Cronbach α >0.8). Superior discriminative ability was demonstrated by significant differences (p < 0.05) in 2 of 7 scores between neoadjuvant treatment groups, and in 6 of 7 scores between complication groups, none of which were detected by the SF-12 or Functional Assessment of Cancer Therapy-Colorectal surveys. LIMITATIONS: Limitations included a small sample size, cultural differences, and failure to assess test-retest ability of the questionnaire. CONCLUSIONS: The Cleveland Clinic Colorectal Cancer Quality of Life Questionnaire is an efficient and reliable quality-of-life measure that better incorporates factors specific to colorectal cancer surgery. See Video Abstract at http://links.lww.com/DCR/B155. REDUCIENDO LA CARGA AL PACIENTE Y MEJORANDO LA CALIDAD DE DATOS CON EL NUEVO CUESTIONARIO DE CALIDAD DE VIDA EN CÁNCER COLORRECTAL DE CLEVELAND CLINIC (CCF-CAQL): El cuestionario de calidad de vida en cáncer colorrectal de Cleveland Clinic se desarrolló en respuesta a la necesidad de una herramienta nueva, rápida e integral para evaluar la calidad de vida en pacientes con cáncer colorrectal. Los cuestionarios disponibles como SF-12, SF-36, FACT-C y EORTC son demasiado generales para ser informativas o demasiado largas para completar.El objetivo fue validar el cuestionario de calidad de vida colorrectal de la Cleveland Clinic Foundation.Los datos se obtuvieron como parte de un ensayo prospectivo aleatorizado y controlado.Este fue un estudio multicéntrico mundial con dos sedes nacionales y cinco internacionales.Este estudio aleatorizó a 190 pacientes entre las edades de 18 y 80 sometidos a cirugía por cáncer rectal bajo. De aquellos aleatorizados, 142 con encuestas parcialmente completas se analizaron para determinar el sesgo de selección y la aceptabilidad, y 95 con encuestas completas se analizaron para determinar la validez de la encuesta.Los pacientes recibieron un reservorio en J, anastomosis latero-terminal o anastomosis termino-terminal.El estudio evaluó medidas de validez de la encuesta, como el Alfa de Cronbach estandarizado para la consistencia interna y los coeficientes de correlación de Spearman para la validez de construcción, la validez de convergencia y la capacidad de respuesta. Se utilizaron análisis univariados para evaluar la validez discriminativa.Se obtuvo suficiente aceptabilidad, construcción, validez de convergencia, y capacidad de respuesta. Todos los puntajes mostraron una gran consistencia interna (alfa de Cronbach > 0.8). Una capacidad discriminativa superior fue demostrada por diferencias significativas (p < 0.05) en dos de siete puntajes entre grupos de tratamiento neoadyuvante, y en seis de siete puntajes entre grupos de complicaciones, ninguno de los cuales fue detectado por SF-12 o FACT-C.Las limitaciones incluyeron un tamaño de muestra pequeño, diferencias culturales y la falta de evaluación de la confiabilidad test-retest del cuestionario.El Cuestionario de Calidad de Vida en Cáncer Colorrectal de Cleveland Clinic es una medida de calidad de vida eficiente y confiable que incorpora mejor factores específicos asociados a la cirugía de cáncer colorrectal. Consulte Video Resumen en http://links.lww.com/DCR/B155.

Better Function With a Colonic J-Pouch or a Side-to-end Anastomosis?: A Randomized Controlled Trial to Compare the Complications, Functional Outcome, and Quality of Life in Patients With Low Rectal Cancer After a J-Pouch or a Side-to-end Anastomosis.

BACKGROUND INFORMATION: We aimed to compare prospectively the complications and functional outcome of patients undergoing a J-Pouch (JP) or a side-to-end anastomosis (SE) for treatment of low rectal cancer at a 2-year time point after resection for rectal cancer. METHODS: A multicenter study was conducted on patients with low rectal cancer who were randomized to receive either a JP or SE and were followed for 24 months utilizing SF-12 and FACT-C surveys to evaluate the quality of life (QOL). Fecal incontinence was evaluated using the Fecal Incontinence Severity Index (FISI). Bowel function, complications, and their treatments were recorded. RESULTS: Two hundred thirty-eight patients (165 males) were randomized with 167 final eligible patients, 80 in the JP group and 87 in the SE group for evaluation. The mean age at surgery was 61 (range 29 to 82) years. The overall mean recurrence rate was 12 of 238, 5% and similar in both groups. COMPLICATIONS: Overall, 37 of 190 (19%) patients reported complications, 14 of these were Clavien Dindo Grade 3b and 2 were 3a: leak 3 (2 JP,1 SE), fistula 4 (1 JP, 3 SE), small bowel obstruction 4 (3JP, 1 SE), stricture 4 (3 SE, 1 SA), pouch necrosis 2 (JP), and wound infection 5 (2 JP, 3 SE). QOL scores using either instrument between the 2 groups at 12 and 24 months were similar (P > 0.05). Bowel movements, clustering, and FISI scores were similar. CONCLUSION: At time points of 1 and 2 years after a JP or a SE for low rectal cancer, QOL, functional outcome, and complications are comparable between the groups. Although choosing a particular procedure may depend on surgeon/patient choice or anatomical considerations at the time of surgery, SE functions similar to JP and may be chosen due to the ease of construction.

Stromal Cell-Derived Factor 1 Plasmid Regenerates Both Smooth and Skeletal Muscle After Anal Sphincter Injury in the Long Term.

BACKGROUND: Regenerating muscle at a time remote from injury requires re-expression of cytokines to attract stem cells to start and sustain the process of repair. OBJECTIVE: We aimed to evaluate the sustainability of muscle regeneration after treatment with a nonviral plasmid expressing stromal cell-derived factor 1. DESIGN: This was a randomized study. SETTINGS: The study was conducted with animals in a single research facility. INTERVENTIONS: Fifty-six female age-/weight-matched Sprague-Dawley rats underwent excision of the ventral half of the anal sphincter complex. Three weeks later, rats were randomly allocated (n = 8) to one of the following groups: no treatment, 100 µg of plasmid encoding stromal cell-derived factor 1 injected locally, local injection of plasmid and 8 × 10 bone marrow-derived mesenchymal stem cells, and plasmid encoding stromal cell-derived factor 1 injected locally with injection of a gelatin scaffold mixed with bone marrow-derived mesenchymal stem cells. MAIN OUTCOME MEASURES: Anal manometry, histology, immunohistochemistrym and morphometry were performed 8 weeks after treatment. Protein expression of cytokines CXCR4 and Myf5 was investigated 1 week after treatment (n = 6 per group). ANOVA was used, with p < 0.0083 indicating significant differences for anal manometry and p < 0.05 for all other statistical analysis. RESULTS: Eight weeks after treatment, all of the groups receiving the plasmid had significantly higher anal pressures than controls and more organized muscle architecture in the region of the defect. Animals receiving plasmid alone had significantly greater muscle in the defect (p = 0.03) than either animals with injury alone (p = 0.02) or those receiving the plasmid, cells, and scaffold (p = 0.03). Both smooth and skeletal muscles were regenerated significantly more after plasmid treatment. There were no significant differences in the protein levels of CXCR4 or Myf5. LIMITATIONS: The study was limited by its small sample size and because stromal cell-derived factor 1 was not blocked. CONCLUSIONS: A plasmid expressing stromal cell-derived factor 1 may be sufficient to repair an injured anal sphincter even long after the injury and in the absence of mesenchymal stem cell or scaffold treatments. See Video Abstract at http://links.lww.com/DCR/A451.

Regenerating the Anal Sphincter: Cytokines, Stem Cells, or Both?

BACKGROUND: Healing of an anal sphincter defect at a time distant from injury is a challenge. OBJECTIVE: We aimed to investigate whether re-establishing stem cell homing at the site of an anal sphincter defect when cytokine expression has declined using a plasmid engineered to express stromal derived factor 1 with or without mesenchymal stem cells can improve anatomic and functional outcome. DESIGN: This was a randomized animal study. SETTINGS: Thirty-two female age- and weight-matched Sprague Dawley rats underwent 50% excision of the anal sphincter complex. Three weeks after injury, 4 interventions were randomly allocated (n = 8), including no intervention, 100-µg plasmid, plasmid and 800,000 cells, and plasmid with a gelatin scaffold mixed with cells. MAIN OUTCOME MEASURES: The differences in anal sphincter resting pressures just before and 4 weeks after intervention were used for functional analysis. Histology was analyzed using Masson staining. One-way ANOVA followed by the Tukey post hoc test was used for pressure and histological analysis. RESULTS: All 3 of the intervention groups had a significantly greater change in resting pressure (plasmid p = 0.009; plasmid + cells p = 0.047; plasmid + cells in scaffold p = 0.009) compared with the control group. The plasmid-with-cells group showed increased organization of muscle architecture and increased muscle percentage, whereas the control group showed disorganized architecture at the site of the defect. Histological quantification revealed significantly more muscle at the site of defect in the plasmid-plus-cells group compared with the control group, which had the least muscle. Quantification of connective tissue revealed significantly less fibrosis at the site of defect in the plasmid and plasmid-plus-cells groups compared with the control group. LIMITATIONS: Midterm evaluation and muscle morphology were not defined. CONCLUSIONS: At this midterm follow-up, local delivery of a stromal derived factor 1 plasmid with or without local mesenchymal stem cells enhanced anal sphincter muscle regeneration long after an anal sphincter injury, thereby improving functional outcome. See Video Abstract at http://links.lww.com/DCR/A324.

Should we offer ventral rectopexy to patients with recurrent external rectal prolapse?

BACKGROUND: For patients with rectal prolapse undergoing Ventral Rectopexy (VR), the impact of prior prolapse surgery on prolapse recurrence is not well described. PURPOSE: The purpose of this study was to compare recurrence rates after VR in patients undergoing primary and repeat rectal prolapse repairs. DESIGN: This study is a prospective cohort study. METHODS: IRB-approved prospective data registry of consecutive patients undergoing VR for full-thickness external rectal prolapse between 2009 and 2015. MAIN OUTCOME MEASURES: Rectal prolapse recurrence was defined as either external prolapse through the anal sphincters or symptomatic rectal mucosa prolapse warranting additional surgery. Preoperative and postoperative morbidity and functional outcomes were analyzed. Actuarial recurrence rates were calculated using the Kaplan-Meier method. RESULTS: A total of 108 VRs were performed during the study period. Seventy-two were primary and 36 repeat repairs. Seven cases were open, 23 laparoscopic, and 78 robotic. Six cases were converted from laparoscopic/robotic to open. In 63 patients, VR was combined with gynecological procedures. There were no statistical differences between primary or recurrent prolapse for the following: demographics, operative time, concomitant gynecologic procedures, complications, blood loss, and graft material type. Length of stay was longer in patients with a history of prior prolapse surgery (p = 0.01). Prolapse recurrence rates for primary repairs were reported at 1.4, 6.9, and 9.7% and for recurrent prolapse procedures 13.9, 25, and 25% at 1, 3, and 5 years (p = 0.13). Mean length of follow-up was similar between groups. Time to recurrence was significantly shorter in patients undergoing repeat prolapse surgery 8.8 vs 30.7 months (p = 0.03). CONCLUSIONS: VR is a better option for patients undergoing primary rectal prolapse repair.

A posterior anal sling for fecal incontinence: results of a 152-patient prospective multicenter study.

BACKGROUND: The transobturator posterior anal sling (TOPAS) system is a posterior anal sling that is a minimally invasive, self-fixating polypropylene mesh intended to treat fecal incontinence (FI) in women who have failed conservative therapy. OBJECTIVE: We are reporting 1-year outcome in a prospective, multicenter study under investigational device exemption, evaluating this new treatment modality. STUDY DESIGN: A total of 152 women were implanted with the TOPAS system at 14 centers in the United States. FI was assessed preoperatively and at the 12-month follow up with a 14-day bowel diary, Cleveland Clinic Incontinence Scores, and FI Quality of Life questionnaires. Treatment success was defined as reduction in number of FI episodes of ≥50% compared to baseline. Missing bowel diary data were considered treatment failures. The Wilcoxon signed rank test was used to compare changes observed at 12 months vs baseline. RESULTS: Mean age was 59.6 years old (SD 9.7). The mean duration of FI was 110 mo (range 8-712) months. Mean length of the implant procedure was 33.4 (SD 11.6) minutes. Mean EBL was 12.9 (SD 10.5) mL. Average follow-up was 24.9 months. At 12 months, 69.1% of patients met the criteria for treatment success, and 19% of subjects reported complete continence. FI episodes/wk decreased from a median of 9.0 (range 2-40) at baseline to 2.5 (range 0-40) (P < .001). FI days decreased from a median of 5.0 (range 1.5-7) at baseline to 2.0 (range 0-7) (P < .001) over a 7-day period. FI associated with urgency decreased from a median at baseline of 2.0 (range 0-26) to 0 (range 0-14.5) (P < .001). The mean Cleveland Clinic Incontinence Scores decreased from 13.9 at baseline to 9.6 at 12 months (P < .001). FI Quality of Life scores for all 4 domains improved significantly from baseline to 12 months (P < .001). A total of 66 subjects experienced 104 procedure- and/or device-related adverse events (AEs). Most AEs were short in duration and 97% were managed without therapy or with nonsurgical interventions. No treatment-related deaths, erosions, extrusions, or device revisions were reported. The most common AE categories were pelvic pain (n = 47) and infection (n = 26). Those subjects experiencing pelvic pain had a mean pain score (0-10 scale, 0 = no pain) during the 12-month follow-up of 1.2 (SD 2.4). CONCLUSION: The TOPAS system provides significant improvements in FI symptoms and quality of life with an acceptable AE profile and may therefore be a viable minimally invasive treatment option for FI in women.

Electrical Stimulation Followed by Mesenchymal Stem Cells Improves Anal Sphincter Anatomy and Function in a Rat Model at a Time Remote From Injury.

BACKGROUND: We have explored cell-based therapy to aid anal sphincter repair, but a conditioning injury is required to direct stem cells to the site of injury because symptoms usually manifest at a time remote from injury. OBJECTIVE: We aimed to investigate the effect of local electrical stimulation followed by mesenchymal stem cell delivery on anal sphincter regeneration at a time remote from injury. DESIGN AND MAIN OUTCOME MEASURES: With the use of a rat model, electrical stimulation parameters and cell delivery route were selected based on in vivo cytokine expression and luciferase-labeled cell imaging of the anal sphincter complex. Three weeks after a partial anal sphincter excision, rats were randomly allocated to 4 groups based on different local interventions: no treatment, daily electrical stimulation for 3 days, daily stimulation for 3 days followed by stem cell injection on the third day, and daily electrical stimulation followed by stem cell injection on the first and third days. Histology-assessed anatomy and anal manometry evaluated physiology 4 weeks after intervention. RESULTS: The electrical stimulation parameters that significantly upregulated gene expression of homing cytokines also achieved mesenchymal stem cell retention when injected directly in the anal sphincter complex in comparison with intravascular and intraperitoneal injections. Four weeks after intervention, there was significantly more new muscle in the area of injury and significantly improved anal resting pressure in the group that received daily electrical stimulation for 3 days followed by a single injection of 1 million stem cells on the third day at the site of injury. LIMITATION: This was a pilot study and therefore was not powered for functional outcome. CONCLUSIONS: In this rat injury model with optimized parameters, electrical stimulation with a single local mesenchymal stem cell injection administered 3 weeks after injury significantly improved both new muscle formation in the area of injury and anal sphincter pressures.

Outcomes of Sacral Neurostimulation Lead Reimplantation for Fecal Incontinence: A Cohort Study.

BACKGROUND: Adverse events and complications have been reported after sacral neurostimulation for fecal incontinence, which may result in surgical revision and device explantation. Lead reimplantation may be feasible; however, available data regarding outcomes are less robust. OBJECTIVE: The aim of this study was to determine the outcomes of sacral neurostimulation lead reimplantation for fecal incontinence. DESIGN: This was a retrospective review of prospectively collected data. SETTINGS: The study was conducted at 2 clinical sites from a single institution. PATIENTS: Patients with fecal incontinence who underwent sacral neurostimulation implantation or reimplantation between 2011 and 2014 were included in the study. INTERVENTIONS: Sacral neurostimulation reimplantation was the included intervention. MAIN OUTCOME MEASURES: Change in the Cleveland Clinic Florida Fecal Incontinence Score (0 best; 20 worst) in reimplantation as compared with index implantation controls was the main measure. Secondary outcomes included the frequency and type of adverse events and complications. RESULTS: A total of 112 patients underwent either sacral neurostimulation implantation or reimplantation between 2011 and 2014. Ninety-seven patients underwent an index percutaneous nerve stimulation trial, 93 of whom also underwent a stimulator implantation. Fifteen patients underwent lead reimplantation, with 5 performed before stimulator implantation and 10 after stimulator implantation. The index implanted and reimplanted groups had similar demographics, comorbidities, and complication profiles including explantation rates. The most common reason for reimplantation was lead related (6/15), including 4 lead migrations, 1 lead fracture, and 1 lead erosion. Significant decreases in the incontinence score were achieved in each group (index implantation: p < 0.001; reimplantation: p = 0.006). When comparing the efficacy of sacral neurostimulation therapy in decreasing the fecal incontinence score from baseline in each group, patients with an index implantation were found to have a more significant improvement in their incontinence score as compared with the reimplantation group (p = 0.047). LIMITATIONS: This was a retrospective study. A large number of patients with incomplete functional assessment data were excluded from analysis. CONCLUSIONS: The improvements in fecal incontinence are significantly better after index implantation than after reimplantation.

Does Stool Leakage Increase in Aging Pouches?

BACKGROUND: Restorative proctocolectomy with IPAA is the standard surgical option for patients with ulcerative colitis. Although ileal pouches have been shown to have acceptable functional outcomes, some patients experience fecal incontinence. OBJECTIVE: The purpose of this study was to evaluate the incidence of fecal leakage and the way it may change over time in patients with an ileoanal pouch. DESIGN: This study used a retrospective design. SETTINGS: The study was conducted at a tertiary care center. PATIENTS: Patients who received an IPAA for ulcerative colitis between 1983 and 2008 were accessed from a prospectively maintained database. We excluded patients with cancer, colonic dysplasia, and missing record of ileostomy closure and without long-term functional data. MAIN OUTCOME MEASURES: We defined fecal leakage as leakage of stool more than once per day. Univariate and multivariate analyses were performed to identify associations with and possible risk factors for fecal leakage. RESULTS: A total of 1228 patients were included in this study. There were 656 men, with a mean age of 38.7 years. The median follow-up time was 158 months. The fecal leakage rates at 5, 10, and >15 years were 24.6%, 25.7%, and 27.4% (p = 0.66). Patients with fecal leakage were significantly older at the time of surgery (p < 0.001), had longer disease duration before surgery (p = 0.04), underwent more 2-stage surgery (p = 0.04), included more women (p < 0.01), and showed lower preoperative maximum anal squeeze pressure (p = 0.008). On multivariate analysis, the only significant factor predisposing to fecal leakage was older age at the time of pouch surgery (OR = 1.07 (95% CI, 1.02-1.12); p = 0.005). LIMITATIONS: The study was limited by its retrospective and non-randomized nature. CONCLUSIONS: The occurrence of fecal leakage in patients with IPAA does not change with time. However, increased age at the time of surgery may increase the chances of patients with IPAA having fecal leakage.

Current status: new technologies for the treatment of patients with fecal incontinence.

Fecal incontinence is a frequent and debilitating condition that may result from a multitude of different causes. Treatment is often challenging and needs to be individualized. During the last several years, new technologies have been developed, and others are emerging from clinical trials to commercialization. Although their specific roles in the management of fecal incontinence have not yet been completely defined, surgeons have access to them and patients may request them. The purpose of this project is to put into perspective, for both the patient and the practitioner, the relative positions of new and emerging technologies in order to propose a treatment algorithm.

Effects of acute selective pudendal nerve electrical stimulation after simulated childbirth injury.

During childbirth, a combinatorial injury occurs and can result in stress urinary incontinence (SUI). Simulated childbirth injury, consisting of vaginal distension (VD) and pudendal nerve crush (PNC), results in slowed recovery of continence, as well as decreased expression of brain-derived neurotrophic factor (BDNF), a regenerative cytokine. Electrical stimulation has been shown to upregulate BDNF in motor neurons and facilitate axon regrowth through the increase of ß(II)-tubulin expression after injury. In this study, female rats underwent selective pudendal nerve motor branch (PNMB) stimulation after simulated childbirth injury or sham injury to determine whether such stimulation affects bladder and anal function after injury and whether the stimulation increases BDNF expression in Onuf's nucleus after injury. Rats received 4 h of VD followed by bilateral PNC and 1 h of subthreshold electrical stimulation of the left PNMB and sham stimulation of the right PNMB. Rats underwent filling cystometry and anal pressure recording before, during, and after the stimulation. Bladder and anal contractile function were partially disrupted after injury. PNMB stimulation temporarily inhibited bladder contraction after injury. Two days and 1 wk after injury, BDNF expression in Onuf's nucleus of the stimulated side was significantly increased compared with the sham-stimulated side, whereas ß(II)-tubulin expression in Onuf's nucleus of the stimulated side was significantly increased only 1 wk after injury. Acute electrical stimulation of the pudendal nerve proximal to the crush site upregulates BDNF and ß(II)-tubulin in Onuf's nucleus after simulated childbirth injury, which could be a potential preventive option for SUI after childbirth injury.

Colectomy for slow transit constipation: effective for patients with coexistent obstructed defecation.

BACKGROUND: Patient selection is a crucial step when considering total abdominal colectomy and ileorectal anastomosis (TAC/IRA) for refractory constipation. PURPOSE: This study aimed to evaluate the results of short- and long-term outcomes for patients with pure slow transit constipation (STC) compared to those with slow transit and features of obstructive defecation (STC + OD). METHODS: This study included all patients who underwent TAC/IRA for constipation from 1999-2010. Patients were divided into two groups: group A (STC) and group B (STC + OD) based on abnormal physiology or motility testing in addition to the surgeon's clinical impression of symptomatic obstructive defecation. Demographics, operative variables, and short-term outcomes were collected by retrospective chart review and were compared between groups. Long-term functional outcomes were assessed by telephone survey. This included: number of bowel movements, use of laxatives, antidiarrheal medications, and surgery satisfaction. Validated questionnaires were collected postoperatively. RESULTS: One hundred forty-four patients (143 females; mean age, 40 (18-68) years old) underwent TAC/IRA by either laparoscopic (63 (44 %)) or open (81 (56 %)) techniques. One hundred three patients had pure STC and 41 had STC + OD. Four patients underwent TAC with end ileostomy at first procedure. Seven patients underwent surgery after a trial of diverting ileostomy. One patient died unexpectedly, 2 days after uneventful surgery. Median follow-up was 43 (IQR, 16-75) months. Five (5 %) patients in group A and two (5 %) in group B underwent subsequent ileostomy for poor functional outcomes. Eighty-eight (68 %) patients were available by telephone. Short- and long-term outcomes were equivalent in both groups as well as patient satisfaction (89 vs. 85 %, p = 0.7). CONCLUSIONS: Total abdominal colectomy can be offered to selective patients with slow transit constipation and obstructive defecation with equivalent long-term results.

The Effect of Dosing of Stromal Cell-Derived Factor 1 on Anal Sphincter Regeneration.

Aim: The aim of this study is to investigate if a high dose of the stromal cell-derived factor-1 (SDF-1) plasmid improves outcome in a minipig model of chronic anal sphincter injury. Methods: Twenty-two female minipigs underwent excision of the posterior hemicircumference of the anal sphincter complex and were allowed to recover for 6 weeks. They were randomly allocated (n = 6) to receive either 5% dextrose (sham) or 2, 4, or 8 mg of SDF-1 plasmid at the defect site. Two control pigs received no surgery/treatment. Outcome measures included anal manometry at preinjury/pretreatment and 2, 4, and 8 weeks after treatment, recording the mean of eight pressure channels and the posterior channel alone, histopathology using Masson's trichrome, and immunohistochemistry using PGP9.5 for staining of neural structures, and CY3 staining for blood vessels. Data are expressed as mean ± standard error. Manometry analysis used two-way analysis of variance (ANOVA) followed by the Holm-Sidak test. Quantification of muscle/fibrosis was analyzed with a Kruskal-Wallis one-way ANOVA on ranks. Results: Posterior anal pressures were significantly decreased in sham treated animals compared with controls (p = 0.04). In contrast, mean anal pressures at the four time points were not significantly different between groups (p > 0.05). The defect area of the sham treated group showed irregular muscle bundles, while all three SDF-1 treatment groups show organized muscle bundles, with the most organization in the higher dose groups. Quantification of Masson-stained slides showed no statistically significant differences between groups, but did show increased muscle volume in the area of defect in the treatment groups compared with sham. PGP9.5 and CY3 staining showed increased fluorescence in the higher dose groups compared with sham treatment. Conclusion: A single higher dose of the plasmid encoding SDF-1 may increase muscle volume in the area of a chronic defect. Impact statement Fecal or bowel incontinence as a result of a torn anal sphincter complex remains undetected for many years. The resulting defect does not respond well to surgical repair. Regenerating the anal sphincter complex with functional muscle has been a long-term goal. Stem cells home to a site of a chronic injury and cause regeneration when a cell signaling mechanism is available. Stromal cell-derived factor-1 is one such cytokine that has been well researched by us and others to have this effect. It is easy to use clinically and has been used in other applications in humans and considered safe.

Electrical stimulation of anal sphincter or pudendal nerve improves anal sphincter pressure.

OBJECTIVE: Stimulation of the pudendal nerve or the anal sphincter could provide therapeutic options for fecal incontinence with little involvement of other organs. The goal of this project was to assess the effects of pudendal nerve and anal sphincter stimulation on bladder and anal pressures. DESIGN: Ten virgin female Sprague Dawley rats were randomly allocated to control (n = 2), perianal stimulation (n = 4), and pudendal nerve stimulation (n = 4) groups. A monopolar electrode was hooked to the pudendal nerve or placed on the anal sphincter. Aballoon catheter was inserted into the anus to measure anal pressure, and a catheter was inserted into the bladder via the urethra to measure bladder pressure. Bladder and anal pressures were measured with different electrical stimulation parameters and different timing of electrical stimulation relative to spontaneous anal sphincter contractions. RESULTS: Increasing stimulation current had the most dramatic effect on both anal and bladder pressures. An immediate increase in anal pressure was observed when stimulating either the anal sphincter or the pudendal nerve at stimulation values of 1 mA or 2 mA. No increase in anal pressure was observed for lower current values. Bladder pressure increased at high current during anal sphincter stimulation, but not as much as during pudendal nerve stimulation. Increased bladder pressure during anal sphincter stimulation was due to contraction of the abdominal muscles. CONCLUSION: Electrical stimulation caused an increase in anal pressures with bladder involvement only at high current. These initial results suggest that electrical stimulation can increase anal sphincter pressure, enhancing continence control.

Low current electrical stimulation upregulates cytokine expression in the anal sphincter.

AIM: Stem cells are an emerging treatment for regeneration of damaged anal sphincter tissues. Homing to the site of injury can be potentiated by stromal derived factor 1 (SDF-1) and monocyte chemotactic protein 3 (MCP-3) expression. The effects of electrical stimulation (ES) on upregulation of these cytokines were investigated. METHODS: The anal sphincter complex of Sprague Dawley rats was stimulated with current of 0.25 mA, pulse duration of 40 pulses/s, pulse width of 100 µs, and frequency of 100 Hz for 1 or 4 h. Sham was created using the same needle which was inserted into the anal sphincter without electrical stimulation in different groups of animals. The rats were euthanized immediately or 24 h after stimulation. Cytokine analysis was performed using real-time polymerase chain reaction. Statistical analysis was performed. RESULTS: Results are presented as a fold increase compared to sham that was normalized to 1. SDF-1 and MCP-3 immediately after 1 h were 2.5 ± 0.77 and 3.1± 0.93 vs. sham, respectively, showing significant increase. After 1-h stimulation and euthanasia 24 h after, SDF-1 and MCP-3 were 1.49 ± 0.16 and 1.51± 0.14 vs. sham, respectively, showing significant increase. Immediately and 24 h after 4-h stimulation, SDF-1 was 1.21 ± 0.16 and 0.54 ± 0.16 vs. sham, respectively, and was not significantly different. Immediately and 24 h after 4-h stimulation, MCP-3 was 1.29 ± 0.41 and 0.35 ±1.0 vs. sham, respectively, and was not significantly different. SDF-1 and MCP-3 after 1 h were significantly higher than after 4 h of stimulation at both time points. CONCLUSION: Electrical stimulation for 1 h significantly upregulates SDF-1 and MCP-3 expression that persists for 24 h. Prolonged stimulation reduced chemokine expression, suggesting electrolysis of cells.

Stromal cell derived factor 1 plasmid to regenerate the anal sphincters.

The aim of this study was to evaluate regeneration of a chronic large anal sphincter defect in a pig model after treatment with a plasmid encoding Stromal Cell Derived Factor-1(SDF-1). METHODS: Under ethics approved protocol 19 age/weight matched Sinclair mini-pigs were subjected to excision of the posterior 50% of anal sphincter muscle and left to recover for 6 weeks. They were randomly allocated to receive either saline treatment (Saline 1 ml, n = 5), 1 injection of SDF-1 plasmid 2 mg/ml (1 SDF-1, n = 9) or 2 injections of SDF-1, 2 mg/ml each at 2 weeks intervals (2 SDF-1, n = 5). Euthanasia occurred 8 weeks after the last treatment. In vivo outcomes included anal resting pressures done under anesthesia pre-injury, pre-injection and before euthanasia (8 weeks after treatment). Anal ultrasound was done pre injury and pre-euthanasia. Tissues were saved for histology and analyzed quantitatively. Two way ANOVA followed by Holm-Sidak test and one way ANOVA followed by the Tukey test were used for data analysis, p < 0.05 was regarded as significant. RESULTS: Posterior anal pressures at the 3 time points were not significantly different in the saline group. In contrast, post-treatment pressures in the 1 SDF-1 group pressures were significantly higher than both pre-injury (p = 0.001) and pre-treatment time points (p = 0.003). At the post-treatment time point, both 1 SDF-1 (p = 0.01) and 2 SDF-1 (p = 0.01) groups had significantly higher mean pressures compared to the saline group. Histology showed distortion of normal anatomy with patchy regeneration in the control group while muscle was more organized in both treatment groups. CONCLUSIONS: Eight weeks after a single or two doses of SDF-1injected into a chronic anal sphincter injury improved resting anal pressures and regenerated muscle in the entire defect. SDF-1 plasmid is effective in treating chronic defects of the anal sphincter in a large animal and could be clinically translated.