Colonoscopy for screening and follow up of patients with a family history of colorectal cancer.

OBJECTIVE: To determine the minimum family history of colorectal cancer (CRC), which justifies colonoscopy and to establish whether further colonic assessment is necessary after a negative screening colonoscopy. METHOD: A retrospective review of every colonoscopy undertaken for family screening at the Royal Berkshire and Battle Hospitals, Reading between October 1996 and July 2004. RESULTS: Four hundred and thirty-two patients (261 women) with an average age of 48 years (range 14-84) were screened. Three cancers in patients over the age of 60 years and 49 adenomas were found in 37 patients. Twenty three of 281 (8%) patients with a 'low-risk' family history (one in 12 or less lifetime risk of developing CRC) had either a cancer or an adenoma. Eighteen of 151 (12%) patients with a 'high-risk' family history (one in 10 or greater) had a similar positive colonoscopy. Thirteen of 15 patients who had an adenoma aged under 45 years had a high-risk family history. Seventy-three patients subsequently underwent two or more follow-up colonoscopies. There were 22 adenomatous polyps found in 12 patients (16%) at the first screening, nine adenomas in seven patients in the second colonoscopy and four adenomas found in four patients in all subsequent colonoscopies. CONCLUSION: Patients with a low-risk family history have a similar adenoma pick-up to that of the general population. These patients need not be screened below the age of 50 unless symptomatic. Follow up of low-risk family history (FH) patients with a negative screening colonoscopy is unlikely to be beneficial.

Alverine citrate fails to relieve the symptoms of irritable bowel syndrome: results of a double-blind, randomized, placebo-controlled trial.

BACKGROUND: Alverine citrate has been used in the treatment of irritable bowel syndrome for many years. AIMS: To compare the efficacy and safety of a new formulation of alverine citrate, a 120-mg capsule, with placebo given three times daily for 12 weeks. METHODS: One hundred and seven patients with irritable bowel syndrome were entered into this three-centre, double-blind, randomized, placebo-controlled, parallel group trial. The primary end-point was relief of abdominal pain indicated by improvement in the scores for severity and frequency. Secondary efficacy variables included scores for other clinical symptoms and for overall well-being. RESULTS: The severity and frequency of abdominal pain improved in 66% and 68% of patients treated with alverine citrate vs. 58% and 69% of the placebo group, but these differences were not significant. The mean percentage reduction in the scores for abdominal pain from baseline to the final assessment, although greater in the alverine citrate group (43.7%) compared with the placebo group (33.3%), was not statistically significant. CONCLUSIONS: Alverine citrate is no better than placebo at relieving the symptoms of irritable bowel syndrome. Future trials should be designed to take into account the high and persistent placebo response seen in this condition.

Do steroids help jaundice caused by primary sclerosing cholangitis?

The management of jaundice in patients with primary sclerosing cholangitis (PSC) is clinically challenging. In patients in whom the recognized precipitants for jaundice have been excluded, the outlook is uncertain at best. Some improve spontaneously, but the only treatment demonstrated to be effective is liver transplantation--which may not always be appropriate. We report three cases of jaundice in patients with PSC in whom corticosteroid therapy appeared to be beneficial.

Rapid symptom relief in reflux oesophagitis: a comparison of lansoprazole and omeprazole.

BACKGROUND: Lansoprazole, a substituted benzimidazole, is a proton pump inhibitor which is highly effective in the control of 24-h intragastric acidity. The aim of this multicentre, randomized, double-blind study was to compare lansoprazole 30 mg once daily and omeprazole 20 mg once daily in the symptom relief and healing of patients with reflux oesophagitis. METHODS: Six hundred and four patients with endoscopically proven oesophagitis and a recent history of heartburn were randomly assigned to receive lansoprazole 30 mg or omeprazole 20 mg daily for 4-8 weeks. Daily assessment of symptoms was made by the patient using a 100-mm Visual Analogue Scale. Clinical symptoms were evaluated at weeks 0, 1, 4 and 8. Endoscopic assessment of healing, defined by normalization of the oesophageal mucosal appearance, was made at weeks 4 and 8. RESULTS: Two hundred and eighty-two patients in the lansoprazole group and 283 patients in the omeprazole group were eligible for inclusion in the per protocol analysis. At 3 days, there was a significant improvement in daytime symptoms of heartburn for patients in the lansoprazole group compared with the omeprazole group (P = 0.05). A similar but non-significant trend was seen at 7 days (P = 0.18). Clinical assessment at 7 days demonstrated significant improvement in daytime epigastric pain in the lansoprazole group compared with the omeprazole group (P = 0.03), with a similar but non-significant trend in night-time epigastric pain (P = 0.07). Healing rates of oesophagitis at 4 and 8 weeks were 70 and 87%, respectively, with lansoprazole, and 63 and 82%, respectively, with omeprazole. Logistic regression analysis of the cumulative healing rates, which included baseline factors affecting outcome, resulted in an odds ratio of 1.46 (95% CI = 0.87-2.45), suggesting a higher chance of being healed with lansoprazole treatment compared with omeprazole treatment. A total of 615 adverse events were reported by 308 (51%) patients during the study period. The majority of events were mild in nature and the incidence was similar in both treatment groups. The most frequently reported events were headache, diarrhoea and nausea. CONCLUSION: Lansoprazole provides greater symptom relief compared with omeprazole during the first week of treatment. Both treatments were effective in healing oesophagitis.

Mucin depletion in inflammatory bowel disease.

The mucin and gland content of 26 rectal biopsy specimens--five normal specimens, 10 from patients with ulcerative colitis, and 11 from patients with Crohn's disease--were measured using a Quantimet image analyser. There was significantly less mucin in the groups with ulcerative colitis compared with either those with Crohn's disease or the normal controls. The difference in the gland content between the groups with ulcerative colitis and Crohn's disease and between the group with Crohn's disease and the normal controls did not reach significance. The results suggest that it is worth while assessing the mucin content of rectal biopsy specimens from patients with inflammatory bowel disease. In routine practice this assessment can be made by eye using a suitably stained section.

Favourable response to conservative surgery for extra-pancreatic gastrinoma with lymph node metastases.

Five patients with the Zollinger-Ellison syndrome who had extra-pancreatic (duodenal or paraduodenal) gastrinoma with lymph node metastases responded favourably to simple excision or mere shelling out of macroscopic tumour. Acid studies, serum gastrin and the secretin test became normal in all cases in the immediate postoperative period and remained so in three of the five patients when tested at 57, 33 and 8 months. The tests became abnormal in two patients when tested 8 and 53 months after surgery, but both patients are currently well-controlled on ranitidine 150 mg b.d. 22 and 65 months respectively after surgery. These results suggest that in patients with extra-pancreatic gastrinoma who have lymph node metastases simple excision of all macroscopic tumours may offer the prospect of long-term control. The place of total gastrectomy in such patients is questioned.

Comparison of the oral (PABA) pancreatic function test, the secretin-pancreozymin test and endoscopic retrograde pancreatography in chronic alcohol induced pancreatitis.

The oral (PABA) pancreatic function test (PFT), the secretin-pancreozymin test and endoscopic retrograde pancreatography (ERCP) have been carried out in 32 patients with suspected chronic alcohol induced pancreatitis (CAIP) in order to evaluate which, if any, test was most likely to confirm the provisional diagnosis. Thirty one patients had changes of minimal (n = 6) moderate (n = 7) or advanced (n = 18) chronic pancreatitis on pancreatography, whilst one patient had a pancreas divisum. Eight hour urinary PABA excretion was significantly reduced in patients with moderate and advanced structural changes (p less than 0.001) and correlated significantly with all parameters of the PFT, although eight patients with an abnormal pancreatogram and pancreatic function test had a normal PABA value. The PFT was abnormal in 23 patients, but normal in five patients with an abnormal pancreatogram and low PABA value. Most patients with minimal change pancreatitis had a normal PABA test and PFT. We conclude that pancreatography appears to be the most sensitive method for detecting chronic pancreatic damage and for confirming a clinical diagnosis of chronic alcohol induced pancreatitis. Both the PFT and PABA test are useful confirmatory tests and whilst the PFT is slightly more sensitive for assessing pancreatic exocrine function, the PABA test is well tolerated and simple to perform. It may therefore be the complementary investigation of choice for this group of patients.

Small bowel biopsy for malabsorption: comparison of the diagnostic adequacy of endoscopic forceps and capsule biopsy specimens.

Biopsy specimens of the small bowel were obtained from 40 patients suspected of having malabsorption. Four different techniques were used at a single session--namely, endoscopic biopsy of the descending duodenum using paediatric and standard size forceps and suction capsule biopsy of the descending duodenum and the proximal jejunum. Specimens were compared for size, adequacy, and ability to confirm or exclude mucosal abnormality. Fourteen patients had villous atrophy. In all patients four biopsy specimens were obtained with paediatric endoscopic forceps and four with standard endoscopic forceps. No capsule biopsy specimen was retrieved from the duodenum in three patients and from the jejunum in five patients. Specimens were considered to be adequate in 36 patients when paediatric forceps were used, in 39 when standard forceps were used, in 28 on duodenal capsule biopsy, and in 32 on jejunal capsule biopsy. This study indicates that the most reliable method for diagnosing or excluding villous atrophy is endoscopic forceps biopsy of the descending duodenum, provided that at least four specimens are obtained with standard size forceps.

Plasma cell infiltration of the small bowel: lack of evidence for a non-secretory form of alpha-heavy chain disease.

Eight patients with diffuse plasma cell infiltration of the small bowel who had the clinical features of immunoproliferative small intestinal disease (IPSID), but whose serum was negative for free alpha-heavy chains, were investigated for evidence of a non-secretory form of alpha-chain disease (alpha-CD). Molecular sieving and immunoblotting of serum, immunoperoxidase staining of biopsy specimens, and in vitro protein synthesis studies utilising an immunoprecipitation technique and polyacrylamide gel electrophoresis, failed to detect any new cases of alpha-CD. Four of the eight cases were found to have diffuse intestinal lymphoma. The remaining four patients, who were unsuccessfully investigated for evidence of a significant abnormality in cellular immunity, have not developed detectable alpha-CD protein or lymphoma over a mean of 143 months. Despite continuing exposure to possible environmental stimuli, it is concluded that not all cases of IPSID elaborate detectable alpha-CD protein or evolve to lymphoma.

Campylobacter colitis: differentiation from acute inflammatory bowel disease.

We describe 10 patients with campylobacter colitis who gave a characteristic history of an acute diarrhoeal illness, rectal bleeding and colicky abdominal pain. For the majority of patients the clinical and sigmoidoscopic features differentiated campylobacter colitis from acute inflammatory bowel disease. Where doubt remained, evidence of a specific antibody response to campylobacter enabled a presumptive clinical diagnosis to be confirmed.

Vitamin A therapy in patients with Crohn's disease.

Vitamin A therapy has been claimed in isolated reports to be of benefit to patients with Crohn's disease. To investigate this further, 86 patients were entered into a long-term double-blind study of vitamin A, 50,000 U twice daily, as compared with placebo. After a mean of 14.1 mo of treatment there was no significant difference between the groups as measured by a variety of activity indices (including the National Cooperative Crohn's Disease Activity Index), the number of acute attacks, and the surgical rate. No toxic effects of vitamin A were observed during the study. In this study vitamin A has not been shown to be of benefit to patients with Crohn's disease who are in remission.

Conservative surgery in the Zollinger-Ellison syndrome.

Laparotomy failed to show an obvious primary lesion in two patients with the Zollinger-Ellison syndrome (ZES), one of whom had metastatic gastrinoma in a solitary lymph node which was removed. Both patients underwent a truncal vagotomy and pyloroplasty. Postoperative acid studies have shown a marked and sustained diminution in acid hypersecretion which was particularly striking in the patient with a solitary metastatic lymph node. The patient without a detectable lesion is now well-controlled on half the dose of cimetidine required pre-operatively and the other no longer requires therapy. We believe that patients in whom pre-operative investigations have shown no evidence of extensive metastases should undergo laparotomy in the hope of finding a solitary primary or isolated metastatic lesions unassociated with an obvious primary in the pancreas. Available evidence suggests that simple removal of such lesions offers the patient an excellent chance of long-term remission. However, if no such lesion is discovered, vagotomy may be the logical procedure to assist in the subsequent pharmacological control of the acid hypersecretory state.