Francesco Brandara

Randomized clinical trial comparing botulinum toxin injections with 0·2 per cent nitroglycerin ointment for chronic anal fissure

In recent years treatment of chronic anal fissure has shifted from surgical to medical. This study compared the ability of two non‐surgical treatments—botulinum toxin injections and nitroglycerin ointment—to induce healing in patients with idiopathic anal fissure.

Experience with Type A Botulinum Toxin for Treatment of Outlet-Type Constipation

BACKGROUND:Puborectalis syndrome remains a therapeutic challenge for todays physicians. Traditional approaches include use of fiber, laxatives, enemas, biofeedback training, and surgery. These often were tried sequentially and had conflicting or even disappointing results. We investigated the efficacy of injections of botulinum toxin in improving rectal emptying in patients with defecatory disorders involving spastic pelvic-floor muscles.METHODS:Twenty-four consecutive patients with chronic outlet obstruction constipation resulting from puborectalis syndrome were included in the study. The patients were treated with 60 units of type A botulinum toxin, injected into two sites on either side of the puborectalis muscle under ultrasonographic guidance.RESULTS:At 2 months, evaluation inspection revealed a symptomatic improvement in 19 patients. Anorectal manometry demonstrated decreased tone during straining from 98 ± 24 to 56 ± 20 mmHg at a 1-month evaluation (p < 0.01) and 56 ± 29 mmHg at a 2-month follow-up (p < 0.01). Pressure during straining was lower than resting anal pressure at the same time in all patients. Defecography after the treatment showed improvement in anorectal angle during straining, which increased from 98 ± 9° to 121 ± 15° (p < 0.01).CONCLUSIONS:Botulinum toxin injections should be considered as a simple therapeutic approach in patients with obstructed defecation. The treatment is safe and effective, especially with the use of the ultrasonographic guidance that accounts for a more precise injection and consequently better long-term results. Otherwise, given the limited effect of the toxin, repeated injections may be necessary to maintain the clinical improvement.

Outlet type constipation in Parkinson's disease: results of botulinum toxin treatment

Background : Constipation is one of the most common autonomic dysfunctions observed in Parkinsons disease.

End-to-end versus end-to-side stapled anastomoses after anterior resection for rectal cancer.

Sphincter‐saving procedures for resection of mid and, in some cases, of distal rectal tumors have become prevalent as their safety have been established. Increased anastomotic leak rate, associated with the type of anastomosis and the distance from the anal verge, has been reported. To compare surgical outcomes of end‐to‐end and end‐to‐side anastomosis after anterior resection for T1–T2 rectal cancer.

Treating chronic anal fissure with botulinum neurotoxin

Recent reports confirm that the management of chronic anal fissure has undergone extensive re-evaluation during the past few years. This rejuvenation of interest is attributable to the application of neurochemical treatment, which has contributed to the tendency to treat the disease on an outpatient basis. The use of botulinum neurotoxin seems to be a promising and safe approach for the treatment of chronic anal fissure, particularly in patients at high risk for incontinence. Indeed, botulinum neurotoxin has been successfully used selectively to weaken the internal anal sphincter as a treatment for chronic anal fissure. It is also more efficacious than nitrate therapy, and is not related to the patients willingness to complete treatment.

Management of bladder, prostatic and pelvic floor disorders with botulinum neurotoxin.

Since its introduction in the late 1970s for the treatment of strabismus and blepharospasm, botulinum toxin (BoNT) has been increasingly used in the interventional treatment of several other disorders characterized by excessive or inappropriate muscle contractions. The use of this pluripotential agent has extended to a plethora of conditions including: focal dystonia; spasticity; inappropriate contraction in most sphincters of the body such as those associated with spasmodic dysphonia, esophageal achalasia, chronic anal fissure, and vaginismus; eye movement disorders; other hyperkinetic disorders including tics and tremors; autonomic disorders such as hyperhidrosis; genitourinary disorders such as overactive and neurogenic bladder, non-bacterial prostatitis and benign prostatic hyperplasia; and aesthetically undesirable hyperfunctional facial lines. In addition, BoNT is being investigated for the control of the pain, and for the management of tension or migraine headaches and myofascial pain syndrome. BoNT injections have several advantages over drugs and surgical therapies in the management of intractable or chronic disease. Systemic pharmacologic effects are rare; permanent destruction of tissue does not occur. Graded degrees of relaxation may be achieved by varying the dose injected; most adverse effects are transient. Finally, patient acceptance is high. In this paper, clinical experience over the last years with BoNT in urological impaired patients will be illustrated. Moreover, this paper presents current data on the use of BoNT to treat pelvic floor disorders.

Botulinum toxin for recurrent anal fissure following lateral internal sphincterotomy.

The aim of the study was to evaluate the efficacy of botulinum toxin injection in the treatment of recurrent anal fissure following lateral internal sphincterotomy.

Management of bladder, prostatic and pelvic floor disorders

Since its introduction in the late 1970s for the treatment of strabismus and blepharospasm, botulinum toxin (BoNT) has been increasingly used in the interventional treatment of several other disorders characterized by excessive or inappropriate muscle contractions. Over the years, the number of primary clinical publications has grown exponentially, and still continues to increase. It has been shown that BoNT blocks cholinergic nerve endings in the autonomic nervous system but does not block non-adrenergic non-cholinergic responses mediated by nitric oxide (NO).The present paper reviews a number of recent clinical indications for urological and pelvic floor dysfunctions, such as overactive and neurogenic bladder, non-bacterial prostatitis, benign prostatic hyperplasia, chronic anal fissure, or conditions associated to hyperactivity of the puborectalis muscle during straining. These indications provide a new promising palette of indications for future usage of BoNT in clinical practice.

Management of defecation disorders with botulinum neurotoxin

Sirs, We read with interest the review on the management of pelvic floor disorders by Cheung and Wald. This excellent paper confirms that the management of pelvic floor disorders has undergone extensive re-evaluation and renewed emphasis during the past few years. This is attributable to the development of neurochemical treatment. Since the discovery in the late 1970s that botulinum neurotoxin inhibits neuromuscular transmission, this powerful poison has been studied extensively. One of the most recent applications is the treatment of various disorders of the gastrointestinal (GI) tract. 3, 9 Beginning with the pioneering work in the treatment of esophageal achalasia, clinical application has expanded to encompass a range of GI conditions and continues to increase. Botulinum neurotoxin is not only potent in blocking skeletal neuromuscular transmission, but also cholinergic nerve endings in the autonomic nervous system. The capability to inhibit contraction of the GI smooth muscle was first suggested by in vitro observations and later demonstrated in vivo; it has also been shown that botulinum neurotoxin does not block nonadrenergic, noncholinergic responses mediated by nitric oxide (NO). In the section of their review devoted to management of anismus and related conditions, Cheung and Wald state that there are a few reports concerning the injection of botulinum toxin into the anal sphincter for treatment of dyssynergic defecation, and, as yet, there is insufficient evidence for the use of botulinum toxin in patients with pelvic floor dyssynergia. We believe that injection of botulinum toxin may be effective in the treatment of obstructed constipation (Table 1). Furthermore, we believe that botulinum toxin injection is a safe treatment of defecation disorders for patients with Parkinson’s disease. Recent observation indicates that outlet obstruction is the main cause for anterior rectocele in several patients and provides evidence that botulinum toxin may be a remedy for them. We have treated 14 women with anterior rectocele by injection of botulinum toxin into the puborectalis. After 2 months, symptom as well as defecographic improvement was noted in nine patients (64%). All patients were followed for a mean of 18 ± 4 months during which there was no relapse of symptoms in any case. No complications or side effects were observed during follow-up, with the exception of one patient who developed mild incontinence for flatus 15 days after treatment with 100 Botox units of botulinum toxin: incontinence persisted for 1 week and spontaneously disappeared. At the 1-year evaluation, incomplete or digitally assisted rectal evacuation had not been reported by any patient. Rectocele was not found at physical examination. The resting anal pressure (60 ± 19 mmHg; P 1⁄4 0.7) and the maximum voluntary pressure (45 ± 22 mmHg; P 1⁄4 0.9) were not changed compared with baseline values. The pressure during straining (49 ± 12 mmHg) was reduced as compared with baseline values (P 1⁄4 0.01), and was not significantly less than resting pressure (P 1⁄4 0.08). Defecography revealed recurrent rectoceles in four patients, but all of them were asymptomatic. Rectocele depth was 1.9 ± 1 cm (P 1⁄4 0.00001 vs. baseline value) and rectocele area was 3.1 ± 0.9 cm (P 1⁄4 0.00001 vs. baseline value). Anorectal angle was 119 ± 26 (P 1⁄4 0.01 vs. baseline value). Rectocele, herniation of the anterior rectal wall into the lumen of the vagina, is a frequent finding in women patients and its clinical relevance is questionable: from 20 to 81% of both asymptomatic women and patients with constipation may have rectoceles. If less than 2 cm in diameter, rectoceles are usually accepted as a normal finding, both in constipated patients and in healthy subjects, whereas those with a diameter of more than 2 cm can cause outlet obstruction and rectal emptying difficulties. Although it has been suggested that some rectoceles may be caused by failure of relaxation or Aliment Pharmacol Ther 2004; 19: 1131–1136. doi: 10.1111/j.1365-2036.2004.01951.x

Authors' reply: Botulinum toxin for recurrent anal fissure following lateral internal sphincterotomy (Br J Surg 2008; 95: 774–778)

component in this study or in the studies examined by the two meta-analyses. Incontinence following LIS is associated with either extensive division of IAS or inappropriate division of the EAS3. Meta-analysis indicated that incontinence following LIS is 2·3 per cent and, similarly to BTx injection, is mostly transient. We would advocate the use of EAUS and ARP in every female (because occult anal sphincter injury occurs in 35 per cent of normal vaginal deliveries and 80 per cent with forceps deliveries4), and men with recurrent symptoms following LIS, before considering further procedures. J. C. I. Singh, M. Davies, U. Khot, T. V. Chandrasekaran, N. D. Carr and J. Beynon Department of Colorectal Surgery, Singleton Hospital, Sketty, Swansea SA2 8QA, UK DOI: 10.1002/bjs.6399