R. J. Nicholls

Bio: R. J. Nicholls is an academic researcher from Imperial College London. The author has contributed to research in topics: Proctocolectomy & Pouchitis. The author has an hindex of 32, co-authored 59 publications receiving 5020 citations. Previous affiliations of R. J. Nicholls include University of London & St Thomas' Hospital.

Proctocolectomy without ileostomy for ulcerative colitis.

Abstract: An operation has been developed that permits total removal of all disease-prone mucosa in ulcerative colitis but avoids the need for a permanent ileostomy. The colon and upper half of the rectum are excised and the remaining inflamed mucosa is stripped from the rectal stump down to the dentate line of the anal canal. A pouch is fashioned from a triplicated loop of terminal ileum. This is drawn down through the denuded rectum and an anastomosis created, via the per-anal approach, between the ileum just distal to the pouch and the mid-anal canal. A temporary ileostomy is made. Out of eight patients so treated, five were available for assessment, and four of them were highly satisfied with the result in improved health and function. The remaining three were awaiting closure of their ileostomies.

An assessment of inflammation in the reservoir after restorative proctocolectomy with ileoanal ileal reservoir.

Abstract: The significance of inflammation of the mucosa of the ileal reservoir after restorative proctocolectomy is not known although in some cases it appears to be associated with symptoms when the condition has been referred to as pouchitis. This investigation has aimed to determine the prevalence of inflammation, to define pouchitis and to examine some factors which might be related to inflammation. Mucosal biopsies from the ileal reservoir were studied in 90 patients at up to 62 months after closure of the ileostomy. A histological grading system (0–6) was used to assess the severity of inflammation. Some degree of chronic and acute inflammation was found in 87% and 30% of cases respectively. The prevalence of a grade of 4 or more was 23% and 3.5%. There was a correlation between severity of chronic and acute inflammation. Severe histological acute inflammation (grade 4–6) was associated with sigmoidoscopic features of inflammation and with increased frequency of defaecation. Of 55 patients sigmoidoscoped by one clinician, 6 (11%) had pouchitis which was characterised by macroscopic inflammation of the reservoir, diarrhoea and a histological grade of 4 or more. The severity of chronic inflammation was not related to frequency of defaecation. Histological inflammation could not be correlated with the type of reservoir, residual volume after evacuation of a known volume of stool substitute introduced per anum into the reservoir or compliance of the reservoir. Acute inflammation was significantly more severe in patients with ulcerative colitis than in those with familial adenomatous polyposis.

Restorative proctocolectomy with ileal reservoir: pathological and histochemical study of mucosal biopsy specimens.

Abstract: Mucosal biopsy specimens from the ileal reservoirs of 92 patients who had undergone restorative proctocolectomy (12 with familial adenomatous polyposis, 78 with ulcerative colitis, and two with functional bowel disease) were studied. Chronic inflammation was found in almost all, as was villous atrophy of varying severity. Other changes included pyloric metaplasia and mucosal prolapse. Acute inflammatory changes and ulceration were less common but, when present, corresponded to the clinical condition of "pouchitis". A grading system was devised to score acute and chronic inflammatory changes. There was a significant increase in acute inflammatory scores in ulcerative colitis compared with those in familial adenomatous polyposis, and pouchitis was present only in patients who had had ulcerative colitis; the morphological features of pouchitis are similar to those seen in the colorectal mucosa in ulcerative colitis. Histochemical studies of mucin in the reservoirs of mucosa showed that there may have been a change from small intestinal mucin to colonic mucin.

Restorative proctocolectomy with ileal reservoir

Abstract: 119 patients (ulcerative colitis 98, polyposis 20, Hirschsprung's disease 1) were treated between 1976 and 1985. There were 1 operative death (0.8 per cent) and 7 failures (5.9 per cent). Three- (68), two- (13) and four-loop (37) reservoirs were constructed. The ileoanal anastomotic complication rate was 25, 15 and 8 per cent respectively. Mean frequency of defaecation was 4.2 +/- 1.3. Continence was normal in 77 per cent; 4 per cent had a significant faecal leakage. Modification in reservoir design has completely avoided the need to catheterize. Quality of life after the operation was preferred to an ileostomy by 96 per cent of patients with an intact reservoir.

Double-blind crossover trial of metronidazole versus placebo in chronic unremitting pouchitis

Abstract: Metronidazole has been used to treat pouchitis, but there are no controlled data that show it is effective. Chronic unremitting pouchitis is a form of the disorder particularly difficult to manage. Diarrhea is the main symptom of pouchitis, which results from acute inflammation of the mucosa of an ileal reservoir. To test the hypothesis that metronidazole (400 mg thrice daily for seven days) is no better than placebo at reducing stool frequency in chronic unremitting pouchitis, a double-blind placebo-controlled crossover study has been performed. Thirteen patients who had undergone restorative proctocolectomy for ulcerative colitis were studied. The diagnosis of pouchitis was based on clinical, endoscopic, and histological criteria. At entry all patients had symptomatic pouchitis and were passing more than six stools/24 hr or had consistently bloody stools with at least four of six endoscopic criteria of mucosal inflammation. The median frequency of defecation decreased by 3 bowel action/24 hr (conservative 95% confidence intervals 0–4/24 hr) on metronidazole but increased by a median of 1/24 hr on placebo. The difference between the median number of bowel motions, when treatment with metronidazole was compared to placebo, was 4 motions/24 hr (P<0.05) in favor of metronidazole. There was no significant change in the endoscopic or histological grade of inflammation, in the serum C-reactive protein level, or symptomatic scores. In a parallel study, metronidazole did not alter stool frequency in asymptomatic patients without pouchitis who had endoscopically normal reservoirs (six polyposis, six colitis). Metronidazole significantly reduces the frequency of defecation when compared with placebo in chronic pouchitis. The reduction in stool frequency is, however, of limited symptomatic benefit to the patient.

Toward an Integrated Clinical, Molecular and Serological Classification of Inflammatory Bowel Disease: Report of a Working Party of the 2005 Montreal World Congress of Gastroenterology

Abstract: The discovery of a series of genetic and serological markers associated with disease susceptibility and phenotype in inflammatory bowel disease has led to the prospect of an integrated classification system involving clinical, serological and genetic parameters. The Working Party has reviewed current clinical classification systems in Crohn's disease, ulcerative colitis and indeterminate colitis, and provided recommendations for clinical classification in practice. Progress with respect to integrating serological and genetic markers has been examined in detail, and the implications are discussed. While an integrated system is not proposed for clinical use at present, the introduction of a widely acceptable clinical subclassification is strongly advocated, which would allow detailed correlations among serotype, genotype and clinical phenotype to be examined and confirmed in independent cohorts of patients and, thereby, provide a vital foundation for future work.

Guidelines for the management of inflammatory bowel disease in adults

Abstract: Ulcerative colitis (UC) and Crohn’s disease (CD) (collectively termed inflammatory bowel disease (IBD)) are complex disorders reflected by wide variation in clinical practice. These guidelines, commissioned by the Clinical Services’ Committee of the British Society of Gastroenterology (BSG) for clinicians and allied professionals caring for patients with IBD in the United Kingdom, provide an evidence based document describing good clinical practice for investigation and treatment. The guidelines are intended to bring consistency, but should not necessarily be regarded as the standard of care for all patients. Individual cases must be managed on the basis of all clinical data available for that case. Patient preferences should be sought and decisions jointly made between patient and health professional. ### 1.1 Development of guidelines A comprehensive literature search was performed using electronic databases (Medline, PubMed, and Ovid; keywords: “inflammatory bowel disease”, “ulcerative colitis”, and “Crohn’s disease”) by Dr Carter. A preliminary document was drafted by Dr Carter, Dr Lobo, and contributing authors. This was summarised by Dr Travis and revised after circulation first to the committee and then to members of the IBD section of the BSG, before submission to the Clinical Services’ Committee. ### 1.2 Grading of recommendations1 The guidelines conform to the North of England evidence based guidelines development project. The grading of each recommendation is dependent on the category of evidence supporting it: ### 1.3 Scheduled review of guidelines The content and evidence base …