The standard treatments for traumatic and idiopathic faecal incontinence have for the last 10-15 years been sphincter reconstruction and pelvic floor repair, respectively. Results of the treatment of traumatic sphincter lesions have in general been satisfactory, whereas the results after prolonged follow-up of pelvic floor repair for idiopathic anal incontinence seem less convincing. Incontinence due to neurological disorders cannot always be treated by local procedures on the anal sphincter or pelvic floor. This has led to the investigation of a number of other surgical procedures with the aim of re-establishing faecal continence. These include transposition of striated muscles, primarily the gracilis and gluteus maximus, implantation of neuromuscular stimulators, implantation of artificial sphincters and implantation of neuroprosthesis. These new techniques, which are also applicable in patients with traumatic and idiopathic anal incontinence where local reconstructive procedures have failed, are reviewed in this chapter in the light of our present state of knowledge.

The human IAS has particular structural and functional characteristics. This smooth muscle constantly generates rhythmic electrical slow waves, but no action potentials. The slow waves are linked to calcium fluxes and both are essential for mechanical activity, i.e. the ASPW. The IAS is pharmacologically characterized by the presence of alpha excitatory and beta inhibitory adrenergic receptors. Cholinergic drugs have an indirect effect through the release of an inhibitory neurotransmitter, very probably VIP, from NANC nerves. The myogenic activity of the IAS is enhanced by its extrinsic sympathetic innervation. Thus, at rest, the IAS is in a state of partial tetanus and contributes approximately 55% of the MABP. Because the IAS ring cannot be completely closed, the anal mucosa and the haemorrhoidal plexuses fill the gap. By compressing these tissues, the IAS perfectly closes the anal canal to retain not only solids but also fluid stool and gas. Acute rectal distension and rectal activity, mainly through intramural pathways, induce reflex IAS relaxation, permitting the rectal contents to be sampled by receptors in the upper anal canal while continence is temporarily maintained by EAS activity and by expansion of the haemorrhoidal cushions. There is a correlation between the volume of rectal distension and the parameters of IAS relaxation. At maximal IAS relaxation, ASPW are absent, indicating the completeness of the inhibition. Although this RAIR is not essential for defecation, insufficient relaxation may be implicated in constipation. Hyperactivity of the IAS resulting in a high MABP and AUSPW has been considered both as a cause and as an effect in haemorrhoids and anal fissure. Continence for fluids and gas is impaired if IAS activity is decreased (i.e. a low MABP), either by direct trauma or by damage of its sympathetic innervation. Severe faecal incontinence will develop when the contractility of both the IAS and the EAS is affected.

The rectum is insensitive to stimuli capable of causing pain and other sensations when applied to a somatic cutaneous surface. It is, however, sensitive to distension by an experimental balloon introduced through the anus, though it is not known whether it is the stretching or reflex contraction of the gut wall, or the distortion of the mesentery and adjacent structures which induces the sensation. No specific sensory receptors are seen on careful histological examination of the rectum in humans. However, myelinated and non-myelinated nerve fibres are seen adjacent to the rectal mucosa, but no intraepithelial fibres arise from these. The sensation of rectal distension travels with the parasympathetic system to S2, S3 and S4. The two main methods for quantifying rectal sensation are rectal balloon distension and mucosal electrosensitivity. The balloon is progressively distended until particular sensations are perceived by the patient. The volumes at which these sensations are perceived are recorded. Three sensory thresholds are usually defined: constant sensation of fullness, urge to defecate, and maximum tolerated volume. The modalities of anal sensation can be precisely defined. Touch, pain and temperature sensation exist in normal subjects. There is profuse innervation of the anal canal with a variety of specialized sensory nerve endings: Meissner's corpuscles which record touch sensation, Krause end-bulbs which respond to thermal stimuli, Golgi-Mazzoni bodies and pacinian corpuscles which respond to changes in tension and pressure, and genital corpuscles which respond to friction. In addition, there are large diameter free nerve endings within the epithelium. The nerve pathway for anal canal sensation is via the inferior haemorrhoidal branches of the pudendal nerve to the sacral roots of S2, S3 and S4. Anal sensation may be quantitatively measured in response to electrical stimulation. The technique involves the use of a specialized constant current generator and bipolar electrode probe inserted in the anal canal. The equipment is generally available and the technique has been shown to be an accurate and repeatable quantitative test of anal sensation.

Static anal manometry has proved itself a reliable, reproducible and objective assessment of sphincter function in the investigation of disorders of defecation and continence. Despite this, it gives only very limited information on sphincter function due to the unphysiological nature of its measurement. Technical advances, particularly in digital data storage, have made the recording of anal pressure in a normal environment for prolonged periods of time possible. This offers an improved understanding both of anal activity and the interaction of rectal and anal function in normal and pathological states. In normal subjects anal function during a number of normal physiological events such as micturition, passage of flatus and sleep have been investigated. The sampling reflex has been further defined. Abnormalities of the sampling reflex, rectal activity and slow wave activity in the anal sphincter have been demonstrated in a number of pathological conditions of the anorectum and in the states of incontinence or constipation. Effective ambulatory anal manometry remains in its infancy. With continuing advances it offers exciting possibilities in defining normal or abnormal activity of the anorectum and in the investigation of patients with disorders of defecation and continence.

The anal physiology laboratory plays a very important role in the selection of patients for surgical treatment for constipation. Any report which does not include reference to these methods of evaluation will not be helpful since there are several causes of constipation. The current recommended treatment for slow transit constipation is still total abdominal colectomy with ileorectal anastomosis. Treatment of pelvic floor outlet obstruction seems to be best accomplished using muscle/sensory retraining techniques since this is a functional disorder rather than an anatomical or physiological disorder. Combinations of colonic inertia, pelvic floor outlet obstruction and internal intussusception should be treated to correct the pelvic floor outlet obstruction initially, followed by correction of the colonic inertia. In this way failure will be avoided at the time of surgical treatment of the constipation.

Rectal bleeding is the cardinal symptom in patients with inflammation of the rectum, and initial management must be directed at establishing an underlying diagnosis. In many patients in the Western World this will be idiopathic inflammatory bowel disease, although in all cases other causes such as infection must be excluded. Idiopathic proctitis is usually due to either ulcerative colitis or Crohn's disease, and in both conditions corticosteroids, either systemic or topical, provide the mainstay of treatment. The 5-aminosalicylic acid drugs are helpful in both acute and maintenance treatment, again given either systemically or topically, while metronidazole is of value in patients with Crohn's disease. In those with refractory proctitis alternative agents such as azathioprine, immunomodulating drugs and barrier agents may be useful. Severe inflammation of the rectum secondary to pelvic irradiation will also usually respond to topical steroid therapy, although sucralfate enemas may be equally successful; in resistant cases other treatments may be needed. Infective proctitis, when diagnosed, may require treatment with specific antimicrobial agents.

The management of FAP involves treatment of affected individuals and their families. Such an approach is best coordinated by registrars working in dedicated registries, in close collaboration with nurses, physicians, surgeons, clinical geneticists and others who become involved in the care of these patients. The large bowel of patients with FAP should be removed (totally or subtotally) by the third decade of life. Screening of other areas at risk is recommended to document the natural history of extracolonic manifestations and to allow study of the effects of intervention. Despite these other, sometimes life-threatening manifestations, a near to normal life span is possible in the majority of patients with FAP. The aims of management of the individual and of the family are to ensure that their quality of life is optimal, that support is provided in times of emotional need, that anxiety is minimized and that relatives are adequately screened and treated.

It is clear that the nutritional state of patients with inflammatory bowel disease is often impaired and can be improved by the provision of nutritional support. Improvement in nutritional status can be achieved as effectively with enteral as with parenteral nutrition. Nutritional support appears to have no primary therapeutic effect in patients with ulcerative colitis. With regard to nutritional support in Crohn's disease, parenteral nutrition should be restricted to use as supportive rather than primary therapy. Available information now seems to suggest that most of the benefits of parenteral nutrition in Crohn's disease are related to an improvement in nutritional state rather than as primary therapy, and its use should be restricted to the treatment of specific complications of Crohn's disease, such as intestinal obstruction related to stricture formation or short bowel syndrome following repeated resection. Although some doubt exists over the efficacy of oligopeptide-containing elemental and polymeric enteral diets, the present evidence indicates that chemically defined free amino acid-containing elemental diets have primary therapeutic efficacy in the management of acute exacerbations of Crohn's disease. As such, these diets are worthy of therapeutic trial in patients with severe Crohn's disease involving the distal colon and rectum, particularly in those patients who are malnourished and who prove to be resistant to treatment with a combination of topical corticosteroids and 5-aminosalicylic acid-containing compounds. Clinicians should be aware, though, that the beneficial effects are likely to be restricted to the short term, with high relapse rates by 1 year, this being particularly so in patients with distal Crohn's proctocolitis (Teahon et al, 1988). Volatile fatty acid enemas clearly have potential in the management of patients with severe steroid-resistant proctitis. Finally, one of the most important observations made in recent years is the one concerning the large losses of nitrogen that will occur in patients with inflammatory bowel disease treated with corticosteroids in the absence of adequate protein intake (O'Keefe et al, 1989). Hopefully the days of treating patients with severe inflammatory bowel disease with high dose corticosteroids and a peripheral dextrose or dextrose-saline drip have passed into history.

IPAA surgery has evolved to assume a major role in the operative management of CUC and FAP. In experienced centres, the safety of performing this somewhat complex procedure, often in gravely ill patients, has been confirmed. A significant decrease in morbidity has accompanied increased experience and simplification of the operative techniques. Two major issues await resolution. The first has to do with the less than totally predictable functional results of IPAA surgery. While many patients do well, others, for no apparent reason, do poorly with excess frequency, urgency and incontinence. Whether operative modifications or preoperative testing can alter this outcome is at this time unclear. The second issue has to do with the potential long-term sequelae of IPAA surgery. Pouchitis and nutritional and metabolic consequences, including the potential for malignant transformation of ileal mucosa or of retained rectal mucosa, cannot be ignored. At present, these risks seem remote but only long-term follow-up will determine whether IPAA surgery deserves its current enthusiasm.

Although Helicobacter pylori is now recognized as playing an etiologic role in chronic gastritis and peptic ulcer disease, information on the pathogenesis and natural history of infection is limited. A model is proposed in which luminal H. pylori secrete substances that mediate inflammation that is beneficial to the organism but ultimately deleterious for the host; in addition to tissue damage, inflammation also affects gastric secretory function. In this model, the host may attempt to suppress the inflammatory response, and the adequacy of this postulated down-regulation determines pathological and clinical outcome. The effects of the inflammatory process on gastrin-hydrochloric acid homeostasis may be of critical importance in the pathogenesis of peptic ulcer disease. Because the long-term consequences of H. pylori colonization reflect the continued presence of the organism in the host over years or decades, it may be useful to consider this as a "slow" bacterial infection.

The efficacy of prophylactic sclerotherapy is unclear because published studies of prophylactic sclerotherapy have reached conflicting conclusions. Meta-analysis was used to determine the efficacy of prophylactic sclerotherapy of esophageal varices. The meta-analysis included all English-language articles reporting results of randomized controlled trials of prophylactic sclerotherapy in adults. Prophylactic sclerotherapy reduced the 13-month mortality rate by 11% (95% confidence interval, 4%-19%), which represents a 41% relative reduction in mortality rate. Across studies, the mortality rate reductions were positively correlated with the bleeding rate reductions and negatively correlated with complication rates. The pooled mortality reduction remained significant when sensitivity analyses included the interim results from the abstracts and foreign-language articles. Nonetheless, prophylactic sclerotherapy should not be widely applied at present because complication rates are high and less costly treatments are available. Furthermore, all published studies offered more intensive follow-up to treated patients, which may have confounded the results and consistently inflated the benefits of sclerotherapy.

Elucidation of receptors and mediators regulating gastric pepsinogen secretion has lagged behind understanding of the factors that control acid secretion. During the past decade, as a consequence of the development of in vitro models for studying the control of pepsinogen secretion at the cellular level, much information about chief cell receptors and signal-transduction mechanisms has been obtained, including the identification and characterization of receptors for secretin, vasoactive intestinal polypeptide, cholinergic agonists, gastrin, cholecystokinin, peptide YY, and cholera toxin. Moreover, these cell preparations have permitted secretagogue-induced changes in chief-cell calcium concentration, protein kinase C distribution, and phosphoinositide and cyclic nucleotide content to be measured and related to changes in pepsinogen secretion. This article reviews these advances, discusses areas of uncertainty and controversy, and indicates areas for future investigation.

A family with a visceral neuropathy manifested as chronic idiopathic intestinal pseudo-obstruction is reported. Diagnoses were made histologically by simple rectal biopsy. Discrete eosinophilic intranuclear inclusions, diagnostic of a disease known as neuronal intranuclear inclusion disease, were found in the submucosal ganglion cells. Abnormalities of the autonomic nervous system were identified by pupillary examination and electroretinography. In this family, three of four siblings were affected by the disease, which is apparently transmitted from the paternal side. This pedigree was unique for several reasons: (a) diagnosis in multiple members of two generations indicates that this familial visceral neuropathy was expressed in an autosomal dominant manner, (b) central autonomic nervous system abnormalities were detected by eye examination, and (c) the definitive pathological diagnosis was established antemortem by rectal biopsy in all cases.

This article examines associations between gluten, polymorphisms of the major histocompatibility complex, and mucosal pathology representative of the spectrum of gluten sensitivity. Sequences of wheat, rye, and barley prolamins contain recurring tetrapeptide motifs that are predicted to have beta-reverse-turn secondary structure and that, with in vitro assays, appear active. Structural polymorphisms of major histocompatibility complex subloci identify codon switches within the second exon that control the third hypervariable region in the outer domain of the beta chain. Observations of the intestinal response to gluten reveal five interrelated lesions (preinfiltrative, infiltrative, hyperplastic, destructive, and hypoplastic) that are interpretable as cell-mediated immunologic responses. These responses originate in the lamina propria, where a series of antigen-specific inflammatory processes has now been identified. There is no evidence that celiac sprue is a disease of jejunal enterocytes. Furthermore, the role of intraepithelial space lymphocytes in pathogenesis, if relevant, needs further experimental dissection. Also awaiting further definition are polymorphisms of the celiac lymphocyte antigen receptor and their relationship to gliadin oligopeptide(s) and predisposing genes. The nature and basis of nonresponsive celiac sprue require more thoughtful initiatives to elucidate the immunologic mechanism(s) of unresponsiveness and evaluate possible means of reversal. Finally, a more sensible definition of gluten sensitivity (unhampered by qualitative morphological imagery) is ultimately called for in order to accommodate the biomolecular advances addressed in this review.

Endoscopic hemostatic therapy for upper gastrointestinal bleeding is gaining widespread acceptance despite often conflicting results of randomized controlled trials. To examine the effect of endoscopic therapy in acute nonvariceal upper gastrointestinal hemorrhage, a meta-analysis was performed using a computerized search of the English-language literature and a bibliographic review. The methodology, population, intervention, and outcomes of each relevant trial were evaluated by duplicate independent review. Thirty randomized controlled trials evaluating hemostatic endoscopic treatment were identified. Endoscopic therapy significantly reduced rates of further bleeding (odds ratio, 0.38; 95% confidence interval, 0.32-0.45), surgery (odds ratio, 0.36; 95% confidence interval, 0.28-0.45), and mortality (odds ratio, 0.55; 95% confidence interval, 0.40-0.76). When analyzed separately, thermal-contact devices (monopolar and bipolar electrocoagulation and heater probe), laser treatment, and injection therapy all significantly decreased further bleeding and surgery rates. The reductions in mortality were comparable for all three forms of therapy, but the decrease reached statistical significance only for laser therapy. Further examination of subgroups indicated that endoscopic treatment decreased rates of further bleeding, surgery, and mortality in patients with high-risk endoscopic features of active bleeding or nonbleeding visible vessels. Rebleeding was not reduced by endoscopic therapy in patients with ulcers containing flat pigmented spots or adherent clots. Endoscopic hemostatic therapy provides a clinically important reduction in morbidity and mortality in patients with acute nonvariceal upper gastrointestinal hemorrhage.