Interstitial cells of Cajal modulate the tone of the human internal anal sphincter in vitro.

Background: Interstitial cells of Cajal, expressing the proto-oncogene c-kit, have been shown to regulate the spontaneous activity of the gastrointestinal tract. They have been described in the human internal anal sphincter; however, their function is still unclear.

Objective: We examined the effects of the c-kit tyrosine kinase inhibitor imatinib mesylate on sphincter strips to investigate the function of the interstitial cells.

Short-term effects of neoadjuvant chemoradiotherapy on internal anal sphincter function: a human in vitro study.

Background: Neoadjuvant chemoradiotherapy is recommended in the treatment of locally advanced rectal cancer. Studies have suggested that chemoradiotherapy adversely affects anorectal function. However, the functional implication and the underlying neuromyogenic changes involved in radiation-induced damage are poorly understood.

'How I do it': TEM for tumors of the rectum.

Introduction: Transanal endoscopic microsurgery (TEM) has an established role in the management of benign rectal tumors. It also has an expanding role in the management of malignant tumors, which is more demanding for the clinician. It requires accurate histological and radiological assessment and draws on an expert understanding of the nature of local recurrence, metastasis, and the place of adjuvant therapies.

Use of a monoclonal antibody to sucrase-isomaltase for evaluation of the columnar cuff after stapled restorative proctocolectomy.

Purpose: Restorative proctocolectomy with a double-stapled pouch-anal anastomosis retains a cuff of diseased columnar mucosa (columnar cuff) in the upper anal canal that may require biopsy. Biopsying this can be difficult and colonic phenotypic change in the pouch can lead to errors interpreting the histology. This study was designed to investigate the use of a monoclonal antibody to sucrase-isomaltase for differentiating ileal pouch from columnar cuff mucosa.

Fistulating anal Crohn's disease: results of combined surgical and infliximab treatment.

Introduction: Infliximab is a monoclonal antibody against tumor necrosis factor-alpha, which has been shown to be effective in fistulating Crohn's disease. The safety of infliximab in patients with potential perianal sepsis is uncertain. This study was designed to assess the safety and outcome of infliximab therapy combined with surgery for patients with fistulating anal Crohn's disease.

Digital rectal examination of sphincter pressures in chronic anal fissure is unreliable.

Purpose: Chronic anal fissure is said to be associated with internal sphincter hypertonia. However, an unknown proportion of fissures may be associated with normal or even low resting pressures and may subsequently be resistant to pharmacological treatments or at risk from surgical treatments, both of which aim to reduce sphincter hypertonia. This study investigated the ability of surgeons to detect low or normal pressure fissures by digital rectal examination.

Fissurectomy-botulinum toxin: a novel sphincter-sparing procedure for medically resistant chronic anal fissure.

Background: Botulinum toxin heals only approximately one-half of glyceryl trinitrate-resistant chronic anal fissures, perhaps because chemical sphincterotomy alone treats internal sphincter spasm but not chronic fissure fibrosis. We aimed to assess whether a novel procedure, fissurectomy-botulinum toxin, improves the healing rate of medically resistant fissures over that achieved with botulinum toxin alone.

Methods: A prospective pilot study of chronic fissure patients failing medical therapy was undertaken.

Multiple rare variants in different genes account for multifactorial inherited susceptibility to colorectal adenomas.

Clear-cut inherited Mendelian traits, such as familial adenomatous polyposis or hereditary nonpolyposis colorectal cancer, account for <4% of colorectal cancers. Another 20% of all colorectal cancers are thought to occur in individuals with a significant inherited multifactorial susceptibility to colorectal cancer that is not obviously familial. Incompletely penetrant, comparatively rare missense variants in the adenomatous polyposis coli gene, which is responsible for familial adenomatous polyposis, have been described in patients with multiple colorectal adenomas.

Role of nitric oxide in anorectal function of normal and neuronal nitric oxide synthase knockout mice: a novel approach to anorectal disease.

Purpose: In vitro data suggest that nitric oxide is an important inhibitory neurotransmitter in the internal anal sphincter, and morphologic evidence implies that it mediates the rectoanal inhibitory reflex. This study examined the anatomy, physiology, and pharmacology of the internal sphincter in control and neuronal nitric oxide synthase knockout mice.

Methods: Neuronal nitric oxide synthase, nicotinamide adenosine triphosphate dinucleotide phosphate diaphorase histochemistry, and PGP 9.

Clinical features and differential diagnosis of diverticular disease.

Colonic diverticulosis occurs in the majority of Western populations with age, but only a small proportion of people experience symptoms. Diverticular disease usually presents with either haemorrhage or diverticulitis. A quarter of patients with diverticulitis will develop complications including perforation, fistulation, obstruction or stricture.

Recurrence after abdominal surgery for Crohn's disease: relationship to disease site and surgical procedure.

Purpose: We investigated the hypothesis that there is an "aggressive" subtype of Crohn's disease characterized by early recurrence and that disease location and surgical procedure are associated with differing patterns of recurrence.

Methods: We analyzed 280 patient records totaling 482 major abdominal operations from a prospectively compiled Crohn's disease database. Patterns of recurrence, as defined by reoperation, were analyzed by Kaplan-Meier plots and log-rank tests for the group as a whole, as well as according to disease location and operation performed using log-rank and Cox regression analysis.

Phosphodiesterase inhibitors cause relaxation of the internal anal sphincter in vitro.

Purpose: Pharmacologic treatments are gaining widespread acceptance as first-line therapy for anal fissure. However, existing treatments have limited clinical usefulness because of side effects and incomplete healing rates.

Methods: Fresh human surgical resection specimens containing internal anal sphincter and rectal circular muscle were collected.

The physiology, pharmacology and therapeutic manipulation of the internal anal sphincter.

Recent research into the physiology and pharmacology of the internal anal sphincter has elucidated the importance of this structure in health and disease. Its pharmacological manipulation for therapeutic gain has focused mainly on agents to reduce internal anal sphincter tone, a 'chemical sphincterotomy' that might heal chronic anal fissure. However, drugs to increase sphincter tone, and augment intermittent and appropriate relaxation are also being evaluated.