R. K. S. Phillips

A modifying locus for familial adenomatous polyposis may be present on chromosome 1p35-p36.

Mutations of the APC gene cause familial adenomatous polyposis (FAP) in humans and multiple intestinal neoplasia (Min) in laboratory mouse strains. A dominant modifying gene (Mom1), which partially suppresses the min phenotype, has been mapped to mouse chromosome 4. This region is syntenic with human chromosome 1p35-p36. The phospholipase A2 (Pla2s) locus is an excellent candidate for Mom1 and the equivalent human locus PLA2G2A is found on chromosome 1p35. It does not necessarily follow, however, than any modifier of mouse polyposis also influences human disease. In order to test whether a locus on 1p modifies FAP, subjects from 28 FAP families have been typed at microsatellite loci on this chromosome arm. The severity of their duodenal polyposis has also been assessed by endoscopy. Pedigree (lod score) linkage analysis found no evidence of a simple, dominant modifying gene, comparable with the action of Mom1 in inbred mouse strains. Given the more complex genetic and environmental interactions likely to exist in outbred human populations, it is probably more appropriate to use tests which do not specify a mode of inheritance. Using these methods of analysis, the data suggest that a locus on chromosome 1p35-p36 may influence the severity of duodenal FAP.

UPPer Intestinal Surveillance in Familial Adenomatous Polyposis

Our understanding of the natural history of upper gastrointestinal (GI) involvement in familial adenomatous polyposis (FAP) is still evolving, although we know that the main cause of death after colectomy in FAP is upper GI malignancy, affecting 5% of patients. The aim of duodenal surveillance is to target high risk individuals and identify cancers early. We have screened 200 patients prospectively and have observed that duodenal polyposis progresses slowly, but there are some young people who have severe disease who merit close observation. We pay particular attention to endoscopic technique and histological detail, and use a duodenal staging system. Patients are offered randomisation to studies of chemopreventive agents, and those with advanced disease are considered for surgery. Successful management is inhibited by our deficient knowledge of the natural history of upper gastrointestinal polyposis, and by our inability to identify high risk individuals with histological markers rather than because of any technological deficiencies in endoscopic equipment.

Magnetic resonance imaging of the pelvic floor in patients with obstructed defaecation

Background Evacuation proctography and measurements of anorectal physiology are frequently used to clarify the pathophysiology of obstructed defaecation. In some patients these tests are normal, despite convincing clinical evidence of defaecatory difficulty. The aim of this study was to determine whether magnetic resonance imaging (MRI) could reveal pelvic floor abnormality in patients with obstructed defaecation.

Tissue prostaglandin levels in familial adenomatous polyposis patients treated with sulindac

BACKGROUND: Recent work has demonstrated a correlation between frequency of aspirin ingestion and colorectal cancer prevention. Sulindac, another nonsteroidal anti-inflammatory drug (NSAID), has been shown to cause polyp regression and a fall in cell proliferation in patients with familial adenomatous polyposis, who are destined to develop colorectal cancer unless the colon is removed. However, the mode of action of NSAIDs in colorectal carcinogenesis prevention remains to be determined, although a prostaglandin-mediated mechanism seems likely. METHODS: Rectal or duodenal biopsies from 20 patients with familial adenomatous polyposis, who had been randomized to sulindac or placebo, were analyzed for prostaglandin (PG) E2 and E2α levels before and after treatment. RESULTS: A significant fall in prostaglandin E2 and E2α (P=0.0096; PGE2, P=0.036; PGF2α Spearmans rank correlation). CONCLUSIONS: Nonsteroidal antiinflammatory drugs may prevent colorectal cancer by their inhibition of prostaglandin synthesis. Prostaglandins may be implicated in carcinogenesis through an increase in cell proliferation, through immunosuppression, by increasing neovascularization, or via a mutagenic effect.

Randomised controlled trial of metronidazole to reduce pain after day case haemorrhoidectomy

Background: The aim of this study was to investigate the effect of metronidazole on postoperative pain after day-case haemorrhoidectomy (DCH). Method: Forty consecutive patients (17 male) aged 36--65 years (mean 49) randomly received metronidazole (n=20) or placebo in a double-blind manner. All received lactulose 2 days preoperatively. Diathermy haemorrhoidectomy was performed with no anal canal dressing. Patients were discharged on the same day and given diclofenac, 0·2 per cent glycerine trinitrate ointment, lactulose, a contact bleep number, and early outpatient review. Additional analgesics were used as required and patients completed questionnaires for pain, expectation of pain and satisfaction. Results: Overall, patients experienced less pain than expected, except on days 3 and 4. Patients using metronidazole had significantly less pain on days 5, 6 and 7 compared to placebo (P<O·OI, P=0·02 and P<O·OI). Nine patients on metronidazole used additional analgesia compared to \3 on placebo (P=0·34). Return to work was significantly earlier (P=O·OI) with metronidazole (15 days) compared to placebo (18 days). There were two re-admissions (both on placebo), one for faecal impaction, the other secondary haemorrhage. Patient satisfaction was higher in the metronidazole group at weeks I (P=0·OO5), and 6 (P=0·06). Conclusion: prophylactic metronidazole assists DCH by suppressing secondary pain around days 5 to 7 leading to high patient satisfaction and earlier return to work.