Injection of botulinum toxin significantly increases efficiency of fissurectomy in the treatment of chronic anal fissures.

PURPOSE: While acute anal fissures can be treated with topical therapy to reduce sphincter hypertonia (e.g., isosorbide dinitrate, glyceryl trinitrate, diltiazem), chronic fissures may require more invasive instrumental therapy. Currently, the golden standard remains lateral internal sphincterotomy; however, this carries the long-term risk of faecal incontinence. Fissurectomy can be a valuable alternative, but is less efficient because of absence of correction of underlying hypertonia. In this study, we aim to evaluate the additional effect of injection of botulinum toxin during fissurectomy in the treatment of chronic anal fissures. METHODS: A single-centre retrospective analysis of 293 isolated superficial fissurectomies with or without injection of botulinum toxin was performed, with pain relief as primary endpoint. RESULTS: The majority of patients undergoing fissurectomy were women (65%, mean age 45.0 years vs. 35% men, mean age 48.3 years), often because of ventral fissures (30% in women vs. 8% in men). Fissurectomy resulted in resolution of complaints in 81.1%, while additional injection of botulinum toxin resulted in resolution in 90.1% (p < 0.05). Complication rate was identical between the two groups, mainly (flatus) incontinence (4.5% vs 4.9% with botulinum toxin) and post-operative bleeding (1.8% vs 2.5% with botulinum toxin). CONCLUSION: Injection of botulinum toxin significantly increases the efficiency of fissurectomy in the treatment of chronic anal fissures without additional complications.

Analgesic injection of botulinum toxin in anal fissures is efficient and can be performed safely in patients actively receiving chemotherapy.

PURPOSE: Injection of botulinum toxin into the internal anal sphincter is a well-documented intervention to reduce anal hypertonia in the treatment of anal fissures. In patients receiving chemotherapy, painful anal conditions are frequent, secondary to change in bowel habits and reduced immunity. However, injection of botulinum toxin is often not offered due to fear of complications. METHODS: In this retrospective longitudinal observational study, performed in a tertiary hospital setting, we analysed patient characteristics, outcome and complication rates of botulinum toxin injection in patients actively receiving chemotherapy. RESULTS: Twenty-six patients were treated with 20-50 IU botulinum toxin while actively receiving chemotherapy because of intractable pain and hypertonia. The fissure was located dorsally in 69% (n = 18) and ventrally in 19% (n = 5), while in 3 patients (12%), no fissure was documented. The majority of the patients (88%, n = 23) had complete (54%, n = 14) or partial (35%, n = 9) relief of pain. In three patients, additional anal pathology developed in the weeks following botulinum toxin injection: thrombosis of grade IV haemorrhoids, perianal haematoma and an intersphincteric abscess. CONCLUSIONS: Injection of botulinum toxin in the anal sphincters is a safe and effective analgesic option in patients with anal fissure while actively receiving chemotherapy.

Impact of endoscopy system, high definition, and virtual chromoendoscopy in daily routine colonoscopy: a randomized trial.

BACKGROUND: To improve detection of mucosal lesions during colonoscopy a number of imaging modalities have been suggested, including high definition and virtual chromoendoscopy. Given the theoretical advantage of these new imaging techniques, we aimed to investigate their use for the detection of polyps in patients referred for colonoscopy in a large tertiary hospital. METHODS: Demographic, endoscopic, and histological data from 1855 consecutive patients undergoing colonoscopy were collected prospectively. Patients were randomly assigned to three endoscopy systems (Fujinon, Olympus, or Pentax) in combination with four modalities: conventional white-light colonoscopy (n = 505), high definition white-light colonoscopy (n = 582), virtual chromoendoscopy (n = 285) and high definition virtual chromoendoscopy (n = 483). RESULTS: The mean adenoma detection rate (ADR) was 34.9 %, and the adenoma per colonoscopy rate (APCR) was 2.1. No significant differences were noted between the three endoscopy systems. Moreover, no differences in ADR or APCR were observed between the four imaging modalities. High definition white-light colonoscopy resulted in a significantly higher detection of sessile serrated adenomas (8.2 % vs. 3.8 %; P < 0.01) and adenocarcinomas (2.6 % vs. 0.5 %; P < 0.05) compared with the conventional procedure. CONCLUSIONS: No significant differences in ADR or APCR between different endoscopy systems, high definition, and/or virtual chromoendoscopy could be observed in routine colonoscopies in the general population. High definition endoscopy was associated with a significantly higher detection rate of serrated adenomas and adenocarcinomas.

Long-term monitoring of infliximab therapy for perianal fistulizing Crohn's disease by using magnetic resonance imaging.

BACKGROUND & AIMS: Magnetic resonance imaging (MRI) is used to assess the outcome of infliximab (IFX) therapy in patients with perianal fistulizing Crohn's disease (pfCD). However, few long-term data are available about its efficacy. METHODS: We assessed 59 patients with pfCD by MRI and clinical evaluation at baseline. Treated patients then received paired clinical and MRI examinations for a median time period of 36 (11-53.3) weeks. Short-, mid-, and long-term effects of therapy, as well as the ability of MRI to predict treatment outcome and need for surgery, were evaluated. RESULTS: Compared with the baseline MRI, the short-term follow-up MRI (n = 29) revealed a reduced number of fistula tracks in 13.8% and in the inflammatory activity in 55.2% of patients, respectively; mid-term MRI (n = 25) in 56% and in 52%, respectively; and long-term MRI (n = 13) in 15.4% and in 31%, respectively. Improvement of pfCD based on MRI results coincided with clinical improvement in 54.7% of the patients. Short-term and mid-term (but not long-term) MRI showed a significant decrease in the activity score. Therapy outcome was worse among patients with persisting fistulas (P = .01), collections (P = .009), and rectal wall involvement (P = .01) in the final MRI. Patients with single-branched fistulas (P < .0001) and collections (P = .006) in their baseline MRI were more likely to undergo surgery. CONCLUSIONS: MRI is a useful technique for evaluation of pfCD during the first year of follow-up. In the long-term, the MRI improvement coincides with clinical and endoscopic response to IFX in 50% of the patients.

Sacrocolpopexy using xenogenic acellular collagen in patients at increased risk for graft-related complications.

AIMS: We studied the long-term anatomical and functional outcome following sacrocolpopexy for apical vaginal prolapse using xenogenic grafts in a population at increased risk for graft-related complications (GRCs). METHODS: Twenty-two consecutive patients with symptomatic apical prolapse were scheduled for laparoscopic sacrocolpopexy (LSC) with porcine grafts because they were presumed to be at risk for GRC, because of pre-existing vaginal ulcerations (n = 4), concomitant vaginal prolapse repair (n = 15), total hysterectomy (n = 1), or intra-operative abdominal contamination due to accidental laceration of the vagina, bowel perforation (n = 1) or the presence of infection (n = 1). Either small intestinal submucosa (n = 8) or dermal collagen (n = 14) was used. Outcome measures were GRCs, anatomical cure (

Medium term outcome of laparoscopic sacrocolpopexy with xenografts compared to synthetic grafts.

PURPOSE: We compared the medium term anatomical and subjective outcome, and graft related complications after sacrocolpopexy for apical vaginal prolapse using xenogenic or polypropylene grafts. MATERIALS AND METHODS: We prospectively studied 50 consecutive patients who underwent laparoscopic sacrocolpopexy with porcine grafts of small intestinal submucosa (21) or dermal collagen (29). We compared these patients to 100 consecutive controls in whom polypropylene was used, and underwent surgery before (50) or after (50) the cases. The primary outcome was anatomical cure (stage I or less at any compartment). Secondary outcomes were graft related complications, subjective cure and quality of life evaluated by clinical examination, standardized interview and prolapse specific questionnaire, respectively. RESULTS: At study closure 129 (86%) patients were available for functional evaluation and 104 (67%) were available for anatomical evaluation. Mean postoperative followup (+/-33 months) and baseline characteristics except age were comparable. The overall anatomical failure rate was comparable (49% vs 34%, p = 0.053) but failures at the vault (21% vs 3%, p <0.01) and posterior compartment (36% vs 19%, p <0.05) were more frequent in the xenograft group. There were 6 reoperations including secondary laparoscopic sacrocolpopexy (5) and cystocele repair (1), all confined to the xenograft group (p <0.01). Graft related complications were equally frequent (11%) in the xenograft and polypropylene groups. The reoperation rate for graft related complications was not different (xenograft 3% vs controls 11%, p = 0.20). There were no differences in functional outcome and quality of life between xenografts and controls. CONCLUSIONS: While overall anatomical failure was comparable, sacrocolpopexy using xenograft was associated with more apical failures and reoperations for prolapse than with polypropylene without differences in functional outcome. The use of xenografts did not decrease the number of graft related complications.

Cidofovir: clinical experience and future perspectives on an acyclic nucleoside phosphonate analog of cytosine in the treatment of refractory and premalignant HPV-associated anal lesions.

BACKGROUND: Cidofovir, a nucleotide analog with antiviral activity against a broad range of DNA viruses including human papilloma viruses (HPV), is available off label to clinicians. OBJECTIVE: To provide a better knowledge of pharmacology and effects when topically applied. METHODS: After reviewing the chemistry, physiology, and animal studies, an overview of clinical studies is provided. RESULTS/CONCLUSIONS: Cidofovir, as a result of its antiviral and antiproliferative activity and its ability to induce apoptosis, can offer a solution for the treatment of severe recurrent HPV-induced lesions. It can also be used to attempt to treat dysplastic lesions and as an adjuvant treatment. The long-lasting antiviral activity allows infrequent dosing. As a rule, cidofovir applied on the skin is well tolerated, even in long-term treatment. The dose-limiting nephrotoxicity of the drug is not a concern in patients with a glomerular filtration rate within the normal range. Cidofovir has clearly influenced the landscape of refractory and dysplastic anogenital condylomata acuminata and its use has increased over the last decade. However, further controlled clinical trials are needed to assess the role of cidofovir and its derivatives.

Medium-term anatomic and functional results of laparoscopic sacrocolpopexy beyond the learning curve.

BACKGROUND: Limited prospective data on the anatomic and functional outcome after laparoscopic sacrocolpopexy (LSC) are available in the literature. OBJECTIVE: To describe the medium-term anatomic and functional outcome of LSC. DESIGN, SETTING, AND PARTICIPANTS: Prospective consecutive series of 132 women with vaginal vault prolapse undergoing LSC between 2001 and 2006, which was after our learning curve. Patients with urodynamically proven stress incontinence (SI) underwent a concomitant tension-free vaginal tape (TVT) procedure. INTERVENTION: Patients underwent LSC with a polypropylene implant. MEASUREMENTS: Principal outcome measures were anatomic cure (stage 1 or lower) assessed by the Pelvic Organ Prolapse Quantification (POPQ) system and subjective cure and impact on quality of life measured by a standardised interview and, since its introduction in 2004, by a prolapse-specific quality-of-life questionnaire (P-QOL). RESULTS AND LIMITATIONS: At a mean follow-up of 12.5 mo, the anatomic cure rate for the apex was 98%. Anatomic failures elsewhere were mainly at the posterior compartment (18%). Subjective prolapse cure rate was 91.7%, and no patients required reoperation for recurrent prolapse. Symptoms of preoperative SI, urge incontinence, or constipation were cured in 43%, 46%, and 42% of patients, respectively. The rate of de novo SI was 7.3%. De novo constipation developed in 5% and de novo dyspareunia developed in 19%. Patients' quality of life improved significantly. Erosions occurred in 4.5%, all within 1 yr. A limitation of the study is that the quality-of-life assessment score became available halfway through the study, limiting the number of preoperative observations (n=36). CONCLUSIONS: We demonstrated that LSC results in good anatomic outcome and subjective cure of prolapse symptoms at medium term. The posterior compartment was most vulnerable for recurrence.

Prucalopride: the evidence for its use in the treatment of chronic constipation.

INTRODUCTION: Chronic constipation is a common condition that is difficult to treat. Existing options for the treatment of patients with different subgroups of constipation are limited. A new efficacious and safe drug is needed to limit the frequently observed adverse effects induced by laxatives, to improve general wellbeing and quality of life, and to provide an alternative for enemas or even resectional surgery in patients in whom stimulant laxatives cause disabling adverse effects or fail to increase bowel movement frequency. AIMS: The purpose of this article is to assess the current evidence supporting the use of the selective and high affinity serotonin-4 (5-HT(4)) receptor agonist prucalopride in the management of chronic constipation. EVIDENCE REVIEW: There are now convincing data from phase II and multicenter phase III randomized, double-blind, placebo-controlled trials that prucalopride treatment results in a clinically meaningful increase in the number of spontaneous complete bowel movements, a reduction of perceived severity of symptoms and improved disease-related quality of life in a significant proportion of patients. There is a rapid onset of the effect and the improvement is maintained for at least 12 weeks. Prucalopride in a dose of up to 4 mg per day appeared generally well tolerated and devoid of serious cardiac events. Adverse events, most frequently headache and nausea, are usually mild or moderate and occur mainly during the first days of treatment. Prucalopride should be used with prudence and with careful assessment of the benefit-risk ratio until more clinical and electrophysiologic data become available, because relatively few patients have been exposed to the drug for long periods of time. PLACE IN THERAPY: Prucalopride 1-2 mg once daily may be given to patients suffering from chronic constipation for whom laxatives do not provide adequate relief of their symptoms. Patients with severe constipation and slow transit, who frequently develop tolerance to stimulant laxatives, are also eligible for prucalopride treatment.

Posterior intravaginal slingplasty with preservation of the uterus: a modified surgical technique in a young myelomeningocele patient.

We report a case of uterine prolapse in a young woman, treated by posterior intravaginal slingplasty with preservation of the uterus as a feasible and safe surgical procedure. Posterior intravaginal slingplasty is commonly used to correct vaginal vault prolapse, but may be a valuable alternative to correct uterine prolapse. We compare this technique to other techniques to correct uterine prolapse.

Quality of life and illness costs in irritable bowel syndrome.

Quality of life is reduced in patients with irritable bowel syndrome, and the costs for this disease are substantial to society. During a meeting in London, UK, the IBiS club reviewed the literature on these subjects. Drawbacks and advantages with existing instruments to assess quality of life and costs were discussed and the clinical and scientific relevance of the current knowledge was assessed. A summary from the meeting is presented in this paper.

Prucalopride is effective in patients with severe chronic constipation in whom laxatives fail to provide adequate relief. Results of a double-blind, placebo-controlled clinical trial.

BACKGROUND: Chronic constipation (CC) is common and there is a need for more effective and better-tolerated agents that normalize bowel function without affecting secretion. Prucalopride is a novel, selective serotonin(4) receptor agonist with enterokinetic properties. AIMS: Pilot study to compare the efficacy and tolerability of prucalopride and placebo in patients with severe CC referred to a tertiary centre. METHODS: After 4-weeks' run in, patients were randomized to 4 weeks' once daily, double-blind treatment with either prucalopride 4 mg (n = 27) or placebo (n = 26). A 50% dose reduction after 2 weeks' treatment was possible for patients with an excessive gastrointestinal response to the study medication (severe cramps, abdominal pain, and diarrhea). Patients assessed efficacy using a visual analogue scale (VAS) and recorded bowel function in daily diaries. The investigator assessed efficacy and total gut transit time (marker study). RESULTS: Patient VAS assessment demonstrated that prucalopride was significantly more effective than placebo in softening stools, and decreasing straining and time to first stool. Prucalopride also had a positive effect on stool frequency, feeling of complete evacuation and total gut transit time, although these differences were not statistically significant compared with placebo. The most common adverse events were gastrointestinal symptoms and headache; most were mild to moderate. There were no clinically relevant effects on cardiovascular or laboratory parameters. CONCLUSIONS: Once-daily prucalopride 4 mg for 4 weeks is effective and well tolerated in patients with severe CC. It improves whole gut transit, reducing straining, softening stools and reducing time to first bowel movement.

Magnetic resonance imaging of the effects of infliximab on perianal fistulizing Crohn's disease.

OBJECTIVES: Although the clinical efficacy of infliximab as measured by closure of fistulas in Crohn's disease has been demonstrated, its influence on the inflammatory changes in the fistula tracks is less clear. The aim of the present study was to assess the behavior of perianal fistulas before and after infliximab treatment. METHODS: Magnetic resonance imaging (MRI) and clinical evaluation were performed in a total of 18 patients before and after treatment with infliximab. An MRI-based score of perianal Crohn's disease severity was developed using both criteria of local extension of fistulas (complexity, supralavetoric extension, relation to the sphincters and of active inflammation (T2 hyperintensity, presence of cavities/abscesses, and rectal wall involvement). RESULTS: The MRI score was reliable in assessing the fistula tracks, with a good interobserver concordance (p < 0.001). Fistula tracks with signs of active inflammation were found in all 18 patients at baseline and collections in seven. After short-term infliximab treatment, active tracks persisted in eight of 11 patients who had clinically responded to infliximab. After long-term (46 wk) infliximab therapy, MRI signs of active track inflammation had resolved in three of six patients. CONCLUSIONS: We have developed an MRI-based score of perianal Crohn's disease severity to assess the anatomical evolution of Crohn's fistulas. Our study demonstrates that despite closure of draining external orifices after infliximab therapy, fistula tracks persist with varying degrees of residual inflammation, which may cause recurrent fistulas and pelvic abscesses. Whether complete fistula fibrosis occurs over time with repeated infliximab infusions needs further study.