Microbiome diversity predicts surgical success in patients with rectovaginal fistula.

INTRODUCTION AND HYPOTHESIS: Growing literature details the critical importance of the microbiome in the modulation of human health and disease including both the gastrointestinal and genitourinary systems. Rectovaginal fistulae (RVF) are notoriously difficult to manage, many requiring multiple attempts at repair before correction is achieved. RVF involves two distinct microbiome communities whose characteristics and potential interplay have not been previously characterized and may influence surgical success. METHODS: In this pilot study, rectal and vaginal samples were collected from 14 patients with RVF. Samples were collected preoperatively, immediately following surgery, 6-8 weeks postoperatively and at the time of any fistula recurrence. Amplification of the 16S rDNA V3-V5 gene region was done to identify microbiota. Data were summarized using both α-diversity to describe species richness and evenness and ß-diversity to characterize the shared variation between communities. Differential abundance analysis was performed to identify microbial taxa associated with recurrence. RESULTS: The rectal and vaginal microbiome in patients undergoing successful fistula repair was different than in those with recurrence (ß-diversity, p = 0.005 and 0.018, respectively) and was characterized by higher species diversity (α-diversity, p = 0.07 and p = 0.006, respectively). Thirty-one taxa were enriched in patients undergoing successful repair to include Bacteroidetes, Alistipes and Rikenellaceae as well as Firmicutes, Subdoligranulum, Ruminococcaceae UCG-010 and NK4A214 group. CONCLUSIONS: Microbiome characteristics associated with fistula recurrence have been identified. The association of higher vaginal diversity with a favorable outcome has not been previously described. Expansion of this pilot project is needed to confirm findings. Taxa associated with successful repair could be targeted for subsequent therapeutic intervention.

microRNA overexpression in slow transit constipation leads to reduced NaV1.5 current and altered smooth muscle contractility.

OBJECTIVE: This study was designed to evaluate the roles of microRNAs (miRNAs) in slow transit constipation (STC). DESIGN: All human tissue samples were from the muscularis externa of the colon. Expression of 372 miRNAs was examined in a discovery cohort of four patients with STC versus three age/sex-matched controls by a quantitative PCR array. Upregulated miRNAs were examined by quantitative reverse transcription qPCR (RT-qPCR) in a validation cohort of seven patients with STC and age/sex-matched controls. The effect of a highly differentially expressed miRNA on a custom human smooth muscle cell line was examined in vitro by RT-qPCR, electrophysiology, traction force microscopy, and ex vivo by lentiviral transduction in rat muscularis externa organotypic cultures. RESULTS: The expression of 13 miRNAs was increased in STC samples. Of those miRNAs, four were predicted to target SCN5A, the gene that encodes the Na+ channel NaV1.5. The expression of SCN5A mRNA was decreased in STC samples. Let-7f significantly decreased Na+ current density in vitro in human smooth muscle cells. In rat muscularis externa organotypic cultures, overexpression of let-7f resulted in reduced frequency and amplitude of contraction. CONCLUSIONS: A small group of miRNAs is upregulated in STC, and many of these miRNAs target the SCN5A-encoded Na+ channel NaV1.5. Within this set, a novel NaV1.5 regulator, let-7f, resulted in decreased NaV1.5 expression, current density and reduced motility of GI smooth muscle. These results suggest NaV1.5 and miRNAs as novel diagnostic and potential therapeutic targets in STC.

Early Results of a Phase I Trial Using an Adipose-Derived Mesenchymal Stem Cell-Coated Fistula Plug for the Treatment of Transsphincteric Cryptoglandular Fistulas.

BACKGROUND: Management of transsphincteric cryptoglandular fistulas remains a challenging problem and the optimal surgical approach remains elusive. Mesenchymal stem cells, increasingly being utilized for perianal Crohn's disease, offer a novel therapy to treat cryptoglandular fistulas. OBJECTIVES: This study aimed to determine safety and feasibility of using an autologous mesenchymal stem cell-coated fistula plug in patients with transsphincteric cryptoglandular fistulas. DESIGN: This study is a phase I clinical trial. SETTING: This study was conducted at a tertiary academic medical center. PATIENTS: Adult (>18 years) male and female patients with transsphincteric cryptoglandular fistulas were selected. MAIN OUTCOMES MEASURES: The primary outcomes measured were the safety, feasibility, and efficacy of a mesenchymal stem cell-coated fistula plug in patients with transsphincteric fistulas. RESULTS: Fifteen patients (8 women, mean age 39.8 years) with a single-tract transsphincteric fistula received a mesenchymal stem cell-loaded fistula plug and were followed for 6 months. Duration of disease at the time of study enrollment was a median of 3.0 years (range, 1-13 years) with a median of 3.5 (range, 1-20) prior surgical interventions. Adverse events included 1 plug extrusion, 1 abdominal wall seroma, 3 perianal abscesses requiring drainage, and 1 patient with perianal cellulitis. There were no serious adverse events. At 6 months, 3 patients had complete clinical healing, 8 had partial healing, and 4 patients showed no clinical improvement. Radiographic improvement was seen in 11 of 15 patients. LIMITATIONS: This study was limited by the small cohort and short follow-up. CONCLUSIONS: Autologous mesenchymal stem cell-coated fistula plug treatment of transsphincteric cryptoglandular fistulas was safe and feasible and resulted in complete or partial healing in a majority of patients. See Video Abstract at http://links.lww.com/DCR/A897.

Surgery and chemotherapy are associated with improved overall survival in anal adenocarcinoma: results of a national cohort study.

PURPOSE: Anal adenocarcinoma (AAC) is a rare disease with treatment protocols that mimic both that of rectal adenocarcinoma (RAC) and anal squamous cell carcinoma (ASCC). Due to its rarity, data regarding outcomes are lacking. We sought to determine outcomes of patients with AAC compared to RAC and ASCC and to evaluate risk factors for mortality in AAC. METHODS: The United States' National Cancer Database was queried for all adult patients presenting with nonmetastatic AAC, RAC, or ASCC from 2003 to 2011. The primary outcome was overall survival. Intergroup univariate comparisons, unadjusted Kaplan-Meier, and multivariable Cox proportional hazards modeling were used to compare outcomes between AAC, RAC, and ASCC and to identify factors associated with survival within AAC. RESULTS: The query identified 129,153 patients (N = 2117 AAC, 19,427 ASC, 107,609 RAC). AAC patients were less likely than RAC patients to have surgery (72.5 vs. 87.1%), and also less likely to receive chemotherapy (54.7% vs. 96.1%) and radiation (58.2% vs. 74.1%) than patients with ASCC (all p < 0.001). Overall median survival in AAC was 65 months compared to 109 months for RAC and > 120 months for ASCC. On multivariable analysis, independent treatment-related predictors of decreased mortality hazard in AAC included proctectomy (hazard ratio [HR], 0.66) and chemotherapy (HR, 0.60) (both p < 0.001). CONCLUSION: AAC tumors have worse prognosis than either RAC or ASCC. Within patients with AAC, nonsurgical management was independently associated with increased mortality hazard. Patients with AAC should be evaluated in a multidisciplinary setting and referred for surgery.

F-box protein 7 mutations promote protein aggregation in mitochondria and inhibit mitophagy.

The mutations of F-box protein 7 (FBXO7) gene (T22M, R378G and R498X) are associated with a severe form of autosomal recessive juvenile-onset Parkinson's disease (PD) (PARK 15). Here we demonstrated that wild-type (WT) FBXO7 is a stress response protein and it can play both cytoprotective and neurotoxic roles. The WT FBXO7 protein is vital to cell mitophagy and can facilitate mitophagy to protect cells, whereas mutant FBXO7 inhibits mitophagy. Upon stress, the endogenous WT FBXO7 gets up-regulated, concentrates into mitochondria and forms FBXO7 aggregates in mitochondria. However, FBXO7 mutations aggravate deleterious FBXO7 aggregation in mitochondria. The FBXO7 aggregation and toxicity can be alleviated by Proline, glutathione (GSH) and coenzyme Q10, whereas deleterious FBXO7 aggregation in mitochondria can be aggravated by prohibitin 1 (PHB1), a mitochondrial protease inhibitor. The overexpression of WT FBXO7 could lead to FBXO7 protein aggregation and dopamine neuron degeneration in transgenic Drosophila heads. The elevated FBXO7 expression and aggregation were identified in human fibroblast cells from PD patients. FBXO7 can also form aggregates in brains of PD and Alzheimer's disease. Our study provides novel pathophysiologic insights and suggests that FBXO7 may be a potential therapeutic target in FBXO7-linked neuron degeneration in PD.

Rectovaginal fistula repair using a gracilis muscle flap.

INTRODUCTION AND HYPOTHESIS: This video demonstrates a technique for using a pedicled gracilis muscle flap to repair rectovaginal fistula. METHODS: We present the case of a 48-year-old woman diagnosed with rectal cancer 2 years earlier. She underwent neoadjuvant chemoradiation followed by ultralow anterior resection. Six weeks after surgery, a fistula was identified at the anastomotic site. Preoperative planning with urogynecology, plastic surgery, and colon and rectal surgery teams deemed a pedicled gracilis muscle flap to be the best approach for this patient due to the rich blood supply and the patient's prior history of pelvic irradiation. The gracilis muscle is suitable due to the proximity of its vascular pedicle to the perineum, length, and minimal functional donor-site morbidity. We discuss techniques used to interpose a gracilis muscle flap between the rectum and vagina to repair a rectovaginal fistula. CONCLUSION: Using the gracilis muscle is a viable option for repairing rectovaginal fistulas, especially in the setting of prior pelvic radiation. A multispecialty approach may be beneficial in complex cases to determine the optimal approach for repair.

Improving conventional recovery with enhanced recovery in minimally invasive surgery for rectal cancer.

BACKGROUND: Enhanced recovery pathways have been shown to decrease the length of hospital stay in patients undergoing colorectal surgery. Few reports have studied patients undergoing minimally invasive surgery for rectal cancer. OBJECTIVE: Our aim was to review our experience in minimally invasive rectal cancer surgery. We report short-term outcomes and evaluate the potential advantages of the enhanced recovery protocol compared with our less intensive conventional pathway. DESIGN: This is a consecutive retrospective study of all minimally invasive rectal cancers treated from February 2005 to December 2011. Multivariable logistic regression models were constructed to identify factors contributing to a short length of stay. SETTINGS: This study was performed at Mayo Clinic, Rochester, Minnesota, between 2005 and 2011. PATIENTS: A total of 346 patients were retrospectively reviewed. Seventy-eight patients were managed under the enhanced recovery pathway. Patients underwent either laparoscopic-, robotic-, or hand-assisted laparoscopic surgery for rectal cancer. INTERVENTIONS: All patients followed either a standardized conventional pathway or an enhanced recovery pathway for perioperative care. MAIN OUTCOME MEASURES: The primary outcome was the length of stay. Secondary outcomes were postoperative complications and 30-day readmissions. RESULTS: Hospital stay was significantly decreased for patients who underwent minimally invasive surgery for rectal cancer and were managed with an enhanced recovery protocol, 4.1 days, vs 6.1 days for the conventional pathway (95% CI, -2.9 to -1.2 days; p < 0.0001). Rates of complications were similar between the 2 groups. Factors associated with shorter length of stay included the enhanced recovery protocol and laparoscopic or robotic surgery compared with hand-assisted laparoscopic surgery. LIMITATIONS: This was a retrospective study at a single institution. Additional limitations include the comparison with historical controls and the potential for selection bias. CONCLUSION: The enhanced recovery pathway is associated with a significantly decreased length of hospital stay after minimally invasive surgery for rectal cancer in this series. Decreased hospital stay was achieved without affecting short-term outcomes.

How to do an Altemeier perineal rectosigmoidectomy for full-thickness rectal prolapse.

Here, we offer a step-by-step description of the technique for an Altemeier perineal rectosigmoidectomy, which is our institution's preferred perineal approach for patients with full-thickness rectal prolapse. This article is supplemented by a series of high-quality clinical images that are available in Figs S1-S11. The principles of this technique are to excise the rectal prolapse and improve structural support of the pelvic floor.

Comparative effectiveness of biofeedback and injectable bulking agents for treatment of fecal incontinence: Design and methods.

Fecal incontinence (FI), the involuntary passage of stool, is common and can markedly impair the quality of life. Among patients who fail initial options (pads or protective devices, bowel modifying agents, and pelvic floor exercises), the options are pelvic floor biofeedback (BIO), perianal injection with bulking agents (INJ), and sacral nerve electrical stimulation (SNS), which have not been subjected to head-to-head comparisons. This study will compare the safety and efficacy of BIO and INJ for managing FI. The impact of these approaches on quality-of-life and psychological distress, cost effectiveness, and predictors of response to therapy will also be evaluated. Six centers in the United States will enroll approximately 285 patients with moderate to severe FI. Patients who have 4 or more FI episodes over 2 weeks proceed to a 4-week trial of enhanced medical management (EMM) (ie, education, bowel management, and pelvic floor exercises). Thereafter, 194 non-responders as defined by a less than 75% reduction in the frequency of FI will be randomized to BIO or INJ. Three months later, the efficacy, safety, and cost of therapy will be assessed; non-responders will be invited to choose to add the other treatment or SNS for the remainder of the study. Early EMM responders will be re-evaluated 3 months later and non-responders randomized to BIO or INJ. Standardized, and where appropriate validated approaches will be used for study procedures, which will be performed by trained personnel. Prospectively collected data on care costs and resource utilization will be used for cost effectiveness analyses.

Sacral nerve stimulation for fecal incontinence: results of a 120-patient prospective multicenter study.

BACKGROUND: Sacral nerve stimulation has been approved for use in treating urinary incontinence in the United States since 1997, and in Europe for both urinary and fecal incontinence (FI) since 1994. The purpose of this study was to determine the safety and efficacy of sacral nerve stimulation in a large population under the rigors of Food and Drug Administration-approved investigational protocol. METHODS: Candidates for SNS who provided informed consent were enrolled in this Institutional Review Board-approved multicentered prospective trial. Patients showing > or =50% improvement during test stimulation received chronic implantation of the InterStim Therapy (Medtronic; Minneapolis, MN). The primary efficacy objective was to demonstrate that > or =50% of subjects would achieve therapeutic success, defined as > or =50% reduction of incontinent episodes per week at 12 months compared with baseline. RESULTS: A total of 133 patients underwent test stimulation with a 90% success rate, and 120 (110 females) of a mean age of 60.5 years and a mean duration of FI of 6.8 years received chronic implantation. Mean follow-up was 28 (range, 2.2-69.5) months. At 12 months, 83% of subjects achieved therapeutic success (95% confidence interval: 74%-90%; P < 0.0001), and 41% achieved 100% continence. Therapeutic success was 85% at 24 months. Incontinent episodes decreased from a mean of 9.4 per week at baseline to 1.9 at 12 months and 2.9 at 2 years. There were no reported unanticipated adverse device effects associated with InterStim Therapy. CONCLUSION: Sacral nerve stimulation using InterStim Therapy is a safe and effective treatment for patients with FI.

Adenocarcinoma developing at an ileostomy: report of a case and review of the literature.

Primary adenocarcinoma of a permanent ileostomy is a rare and unusual complication. We report a case of primary adenocarcinoma arising at an ileostomy site 46 years after total proctocolectomy for Crohn's colitis. In addition, we performed a literature search and found 36 such cases reported. Based on the results of this case and literature review, we concur with the previously reported theory that the etiology of this phenomenon is likely the result of colonic metaplasia in the ileal mucosa, which eventually progresses to carcinoma. Common presenting symptoms include a bleeding, friable mass, difficulty fitting the stomal appliance, and bowel obstruction. Once confirmed by biopsy, appropriate surgical en bloc excision and stomal relocation is the mainstay of therapy. Lymph node metastasis occurs in 19 percent of patients and survival is at least 85 percent. Adjuvant therapy may be of additional benefit. Patient education is important for early detection as the lesion typically appears an average of 27 years after the original operation.

Segmental vs. extended colectomy: measurable differences in morbidity, function, and quality of life.

PURPOSE: The colon coordinates fecal elimination while reabsorbing excess fluid. Extended colonic resection removes synchronous and prevents metachronous disease but may adversely alter bowel function and health-related quality of life to a greater degree than segmental resection. This study examined the short-term morbidity and long-term function and quality of life after colon resections of different extents. METHODS: Patients undergoing extended resections (n = 201, subtotal colectomy with ileosigmoid or total abdominal colectomy with ileorectal anastomosis) and segmental colonic resections (n = 321) during 1991 to 2003 were reviewed for perioperative outcomes and surveyed for bowel function and quality of life using an institutional questionnaire and a validated quality of life instrument (response rate: 70 percent). RESULTS: The most common indication for extended resections was multiple polyps, and for segmental resections, single malignancy. The complication-free rate was 75.4 percent after segmental resections, 42.8 percent after ileosigmoid anastomosis, and 60 percent after ileorectal anastomosis. Median daily stool frequency was two after segmental resections, four after ileosigmoid anastomosis, and five after ileorectal anastomosis, despite considerable dietary restrictions (55.6 percent) and medication use (19.6 percent daily) after ileorectal anastomosis. Significant proportions of patients felt restricted from preoperative social activity (31.5 percent), housework (20.4 percent), recreation (31.5 percent), and travel (42.6 percent) after ileorectal anastomosis. The overall quality of life after segmental resection, ileosigmoid anastomosis, and ileorectal anastomosis was 98.5, 94.9, and 91.2, respectively. CONCLUSIONS: Measurable compromises in long-term bowel function and quality of life were observed after extended vs. segmental resections. The relative differences in patient-related outcomes should be deliberated against the clinical benefits of extended resection for the individual patient.

Contemporary surgical management of synchronous colorectal liver metastases.

Historically, the 5-year survival rates for patients with stage 4 (metastatic) colorectal cancer were extremely poor (5%); however, with advances in systemic chemotherapy combined with an ability to push the boundaries of surgical resection, survival rates in the range of 25-40% can be achieved. This multimodal approach of combining neo-adjuvant strategies with surgical resection has raised a number of questions regarding the optimal management and timing of surgery. For the purpose of this review, we will focus on the treatment of stage 4 colorectal cancer with synchronous liver metastases.

Outcomes of Rectovaginal Fistula Repair.

OBJECTIVES: Rectovaginal fistulae (RVF) often represent surgical challenges, and treatment must be individualized. We describe outcomes after primary surgical repair stratified by fistula etiology and surgical approach. METHODS: This retrospective cohort study included women who underwent surgical management of RVF at a tertiary care center between July 1, 2001 and December 31, 2013. Cases were stratified according to the following etiology: cancer (RVF-C), inflammatory bowel disease or infectious (RVF-I), and other (RVF-O). Patients with prior surgical treatment of RVF were excluded. Surgical approaches included local (seton, plug), transvaginal or endorectal, abdominal, diversion alone, or definitive (completion proctocolectomy with permanent colostomy or pelvic exenteration). Recurrence-free survival was estimated using the Kaplan-Meier method, and comparisons between subgroups were evaluated based on fitting Cox proportional hazards models. Censoring occurred at last relevant clinical follow-up. Factors contributing to recurrence-free survival were evaluated including age, body mass index, smoking status, fistula etiology, ileostomy, and surgical approach. RESULTS: During the study period, 107 women underwent surgical repair of RVF. The most common fistula etiology was RVF-I (54.2%), followed by RVF-O (23.4%), and RVF-C (22.4%). Ninety-four women underwent fistula repair by the local (29.9%), transvaginal/endorectal (25.2%), abdominal approach (19.6%), or diversion alone (13.1%), whereas 13 underwent definitive surgery (12.2%). Recurrence-free survival was significantly different depending on surgical approach (P < 0.001), but not etiology (P = 0.71). Recurrence-free survival (95% confidence interval) at 1 year after surgery was 35.2% (21.8%-56.9%) for the local approach, 55.6% (37.0%-83.3%) for the transvaginal or endorectal approach, 95% (85.9%-100%) for the abdominal approach, and 33.3% (15%-74.2%) for those with diversion only. CONCLUSIONS: Recurrence rates after RVF repair are high and did not differ by fistula etiology. Abdominal repair of RVF had significantly fewer recurrences.

Synchronous rectal and hepatic resection of rectal metastatic disease.

BACKGROUND: The objectives were to determine the feasibility of combined rectal and hepatic resections and analyze the disease-free survival and overall survival. STUDY DESIGN: Sixty patients who underwent resection for metastatic rectal disease from 1991 to 2005 at Mayo Clinic were reviewed. Inclusion criteria were: rectal cancer with metastatic liver disease and resectability of metastases. The exclusion criteria were: metachronous resection (n = 15). Kaplan-Meier Survival estimated overall survival (OS) and disease-free survival (DFS). Cox proportional hazard models examined the association between groups and survival. RESULTS: The cohort comprised 22 men and 23 women, with median age of 63 years. Surgical management included: abdominoperineal resection, 13 patients (29%); low anterior resection, 29 (64%); local excision, one; total proctocolectomy, one; and pelvic exenteration, one. Major hepatic resection was performed in 22%. There was no mortality, but there were 26 postoperative complications. Disease-free survival from local recurrence at 1, 2, and 5 years was 92%, 86%, and 80%, respectively. Disease-free survival from distant recurrence at 1, 2, and 5 years was 62%, 43%, and 28%, respectively. Overall survival at 1, 2 and 5 years was 88%, 72%, and 32%, respectively. CONCLUSIONS: Combined rectal and hepatic resection is safe. Morbidity and mortality do not preclude concurrent resection. The DFS and OS are comparable to that of patients undergoing a staged procedure.

Management and outcomes of primary coloduodenal fistulas.

PURPOSE: Primary coloduodenal fistula (CDF) is a rare entity. We review our experience with the management and outcomes of CDF. METHODS: This is a retrospective review from 1975 to 2005 of patients with primary CDF. Patients were followed through clinic visits and mail correspondence with a mean (±SE) follow-up of 56 ± 14 months. RESULTS: Twenty-two patients were diagnosed at a mean age of 54 ± 3 years with primary CDF: benign (n = 14) or malignant (n = 8). Benign CDF were due to Crohn's disease (n = 9) or peptic ulcer disease (n = 5); malignant CDF was primarily due to colon cancer (n = 7) plus 1 patient with lymphoma. Indications for operative intervention included intractable symptoms (n = 15), gastrointestinal bleeding (n = 14), and to rule out malignancy (n = 8). Complete resection of malignant CDF with negative margins was achieved in half of patients after en bloc resection. Palliative bypass was performed in those patients with unresectable disease. Thirteen patients with benign CDF had resection of the fistula-2 of these patients required a duodenal bypass. There were no perioperative deaths, and the morbidity rate was 38%. Median survival for patients with malignant CDF was 20 months (range 1-150 months). Two patients with malignant CDF had >5-year survival. All patients with benign CDF who underwent fistula resection had resolution of fistula-related symptoms with one recurrence. CONCLUSION: Benign CDF is amenable to operative therapy with resolution of symptoms and a low recurrence rate. Complete resection of malignant CDF can impart survival benefit.

A fast-track recovery protocol improves outcomes in elective laparoscopic colectomy for diverticulitis.

BACKGROUND: Fast-track (FT) postoperative protocols have been shown to be highly beneficial in open colectomy. Some have questioned the necessity of an FT protocol in the setting of laparoscopic colectomy because hospital stays are short and morbidity is low compared with open surgery. We set out to determine whether an FT protocol has any utility in the setting of elective laparoscopic colectomy. STUDY DESIGN: A retrospective review was conducted on a cohort of 334 patients who underwent elective laparoscopic sigmoid resection for diverticulitis from 1998 to 2008, at Mayo Clinic, a tertiary care center in Rochester, MN. There were 235 patients who were managed with traditional postoperative care, and 99 who were managed with an FT protocol initiated in 2006. The main outcomes measures were time to soft diet, length of stay, overall morbidity, and readmission rate. RESULTS: Times to soft diet (mean 2.3 vs 3.6 days), and first bowel movement (mean 2.6 vs 3.5 days) were shorter in the FT group (p < 0.001). The median lengths of stay were 3 days (interquartile range 3 to 4 days) and 5 days (interquartile range 4 to 6 days) for the FT and non-FT groups, respectively (p < 0.001). Morbidity was significantly lower in the FT group compared with the non-FT group (15.2% vs 25.5%, p < 0.03). The 30-day readmission rate was 2.9% for the FT group and 7.6% for the non-FT group (p = NS). There were no deaths in either group. CONCLUSIONS: Even in patients undergoing laparoscopic colectomy, FT protocols further improve the speed of gastrointestinal recovery, shorten the length of stay, and decrease morbidity.

Infection rates in a large investigational trial of sacral nerve stimulation for fecal incontinence.

INTRODUCTION: Treatment options for patients with fecal incontinence (FI) are limited, and surgical treatments can be associated with high rates of infection and other complications. One treatment, sacral nerve stimulation (SNS), is approved for FI in Europe. A large multicenter trial was conducted in North America and Australia to assess the efficacy of SNS in patients with chronic fecal incontinence. The aim of this report was to analyze the infectious complication rates in that trial. METHODS: Adult patients with a history of chronic fecal incontinence were enrolled into this study. Those patients who fulfilled study inclusion/exclusion criteria and demonstrated greater than two FI episodes per week underwent a 2-week test phase of SNS. Patients who showed a > or = 50% reduction in incontinent episodes and/or days per week underwent chronic stimulator implantation. Adverse events were reported to the sponsor by investigators at each study site and then coded. All events coded as implant site infection were included in this analysis. RESULTS: One hundred twenty subjects (92% female, 60.5 +/- 12.5 years old) received a chronically implanted InterStim Therapy device (Medtronic, Minneapolis, MN, USA). Patients were followed for an average of 28 months (range 2.2-69.5). Thirteen of the 120 implanted subjects (10.8%) reported infection after the chronic system implant. One infection spontaneously resolved and five were successfully treated with antibiotics. Seven infections (5.8%) required surgical intervention, with infections in six patients requiring full permanent device explantation. The duration of the test stimulation implant procedure was similar between the infected group (74 min) and the non-infected group (74 min). The average duration of the chronic neurostimulator implant procedure was also similar between the infected (39 min) and non-infected group (37 min). Nine infections occurred within a month of chronic system implant and the remaining four infections occurred more than a year from implantation. While the majority (7/9) of the early infections was successfully treated with observation, antibiotics, or system replacement, all four of the late infections resulted in permanent system explantation. CONCLUSION: SNS for FI resulted in a relatively low infection rate. This finding is especially important because the only other Food and Drug Administration-approved treatment for end-stage FI, the artificial bowel sphincter, reports a much higher rate. Combined with its published high therapeutic success rate, this treatment has a positive risk/benefit profile.

Long-term functional and quality of life outcomes of patients after repair of large perianal skin defects for Paget's and Bowen's disease.

INTRODUCTION: The assessment of long- term functional and quality of life outcomes of these patients following repair of large defects after surgical excision has not been reported. METHODS: Between 1992 and 2004, at two institutions, 18 patients underwent repair of a perianal defect for Paget's disease (n = 8) or Bowen's disease (n = 10) and were alive with intestinal continuity at last follow-up. Patients were mailed the fecal incontinence quality of life scale (FIQL) and the SF-36. RESULTS: Fourteen patients (78%) responded. Median follow-up for responders was 5 years. Mean age was 65 years with 12 females. Subcutaneous skin flaps (11) and split-thickness skin grafts (three) were used to repair the perianal defects, which were circumferential in 11 patients (79%). Nine patients reported incontinence and completed the FIQL. The FIQL scores of patients reporting incontinence were lower for lifestyle, coping/behavior, and embarrassment but not significantly different for depression compared to patients without incontinence. SF-36 scores of the patients were not significantly different from the normative population. CONCLUSION: Functional results after repair of large perianal defects are acceptable and overall quality of life (QOL) is similar to the normative population although a large proportion of patients have some form of incontinence that impacts certain aspects of their QOL.