Malignant hepatic tumours associated with previous exposure to Thorotrast: four cases.

This report concerns four patients in a district general hospital who died from malignant liver tumours associated with Thorotrast (thorium dioxide) deposits in the liver. Three were known to have had diagnostic angiographic studies performed 36 to 43 years previously using Thorotrast as the contrast agent. In the fourth case no previous relevant information could be obtained. There were two men and one woman with hepatocellular carcinoma and one woman with cholangiocarcinoma. In one of the hepatoma cases there was associated hypercalcaemia of malignancy. Reported latency intervals suggest that cases of Thorotrast-related hepatic malignancy may present up to the second decade of the twenty-first century.

Occupationally related angiosarcoma of the liver in the United Kingdom 1972-1994.

BACKGROUND: Angiosarcoma of the liver (ASL) has been described in vinyl chloride workers worldwide. AIM: To describe the UK experience of occupationally related ASL. PATIENTS: Twenty patients who died from ASL after exposure to vinyl chloride. METHODS: The case records and pathological findings of these 20 patients were reviewed. RESULTS: Twenty men in the United Kingdom aged 37 to 71 years have developed ASL in association with occupational exposure to vinyl chloride monomer VCM in two factories. All had been exposed to VCM for three to 29 years, the tumour developing nine to 35 years after first exposure. Presenting clinical features included abdominal pain, malaise, jaundice, ascites, and massive hepatomegaly. In most cases the disease progressed rapidly, death occurring within a few weeks from hepatic coma. In 17 cases there was no spread outside the liver. In four cases there had been haemorrhage from oesophageal varices due to non-cirrhotic portal fibrosis diagnosed six to 18 years previously. At necropsy the livers of these men showed considerable, often massive, replacement by tumour, apparently multifocal, with necrosis and haemorrhage. CONCLUSIONS: In view of the long latency between exposure and development of the tumour the full extent of ASL occurrence may not be known until 35 years after the introduction of the Code of Practice in 1975.

A randomised trial comparing mesalazine and prednisolone foam enemas in patients with acute distal ulcerative colitis.

Distal ulcerative colitis can be treated with oral or rectal mesalazine, or both. A foam enema preparation has been developed and its efficacy investigated. The aim of this study was to evaluate the efficacy and safety of mesalazine foam enemas compared with prednisolone foam enemas in the treatment of patients with acute distal ulcerative colitis. Patients aged over 18 years presenting with a relapse of distal ulcerative colitis were randomly allocated treatment with mesalazine foam enema (n = 149 evaluable patients) and prednisolone foam enema (n = 146 evaluable patients) for four weeks. A randomised multicentre investigator blind parallel group trial was conducted. It was found that after four weeks of treatment, clinical remission was achieved by 52% of mesalazine treated patients and 31% of patients treated with prednisolone (p < 0.001). There was a trend in favour of more patients in the mesalazine group achieving sigmoidoscopic remission (40% v 31%, p = 0.10). Histological remission was achieved by 27% and 21% of patients receiving mesalazine and prednisolone respectively. Symptoms improved in both treatment groups. Significantly more mesalazine patients had no blood in their stools after four weeks of treatment (67% v 40%, p < 0.001). Prednisolone treated patients had significantly fewer days with liquid stools than mesalazine patients, with a median of 0 and 1 days respectively by week 4 (p = 0.001). In this study mesalazine foam enema was superior to prednisolone foam enema with regards to clinical remission, this was supported by favourable trends in sigmoidoscopic and histological remission rates. Both treatments were well tolerated.

Barrett's esophagus and achalasia. A case report.

A 70-year-old woman with no previous gastroesophageal surgery gave a 6-month history of dysphagia. Barium studies suggested a diagnosis of achalasia. Esophageal manometry showed absence of peristalsis and a high lower esophageal sphincter pressure. Endoscopy showed a dilated esophagus with food residue, and Barrett's esophagus was present. The association of Barrett's esophagus and achalasia must be rare.

Upper gastrointestinal lesions in elderly patients presenting for endoscopy: relevance of NSAID usage.

The occurrence of upper gastrointestinal disease and the relevance of nonsteroidal antiinflammatory drug (NSAID) usage were documented in 511 consecutive patients (321 women, 190 men) over 70 yr old, referred for upper gastrointestinal endoscopy in a district general hospital. The findings were benign esophageal disease (43%), normal (15%), gastric ulcer (11.5%), and duodenal ulcer (11%). Gastric ulcers were more common in women taking NSAIDs (25%) than in NSAID abstainers (7%) p less than 0.001 and male NSAID users (8%) p less than 0.001. Esophagitis and esophageal stricture were not influenced by NSAID usage, but gastric erosions were more common (10% vs. 3%) p less than 0.01. Of 142 patients receiving NSAIDs, 41% presented with hemorrhage, compared with 20.5% of NSAID abstainers (p less than 0.001). Hemorrhage was as common in aspirin takers (15 of 33, 45%) as in standard-dose NANSAID takers (43 of 109, 39%), even though 86% were taking 300 mg of aspirin per day or less. In elderly patients, esophageal disease is common. NSAID use, even low-dose aspirin, is associated with an increased risk of hemorrhage. In females, NSAID usage is associated with gastric ulcer.

Maintenance treatment of duodenal ulceration: ranitidine 300 mg at night is better than 150 mg in cigarette smokers.

Two hundred patients received either ranitidine 150 mg or 300 mg at night for 18 months to prevent duodenal ulcer relapse. Recurrence rates were lower in patients receiving the higher dose of ranitidine (3.1% v 9.7%, p = 0.78; 6.5% v 16.7%, p = 0.037; and 8.9% v 17.0%, p = 0.121 at six, 12, and 18 months respectively). In patients receiving ranitidine 150 mg, recurrences were significantly more common in smokers than non-smokers after 12 and 18 months, while in patients receiving ranitidine 300 mg recurrence rates were similar in smokers and non-smokers. Ranitidine 300 mg at night abolishes the adverse effect of smoking observed during maintenance treatment with ranitidine 150 mg at night and may therefore be an appropriate maintenance dose for smokers who relapse during standard dose maintenance treatment.

Increased occurrence of psoriasis in patients with Crohn's disease and their relatives.

One hundred thirty-six unselected patients with Crohn's disease (43 men, 93 women) were studied for the possibility of psoriasis and questioned regarding their family history, as were 136 controls, matched for age and sex. Psoriasis was present in 13 of the 136 patients with Crohn's disease (9.6%), compared with three of 136 controls (2.2%) (p less than 0.02). Age at onset and anatomical site of Crohn's disease did not influence the result, and there was no difference between the sexes. Fourteen (three with psoriasis) of the 136 Crohn's patients (10%) had a family history of psoriasis in first-degree relatives compared with four of 136 controls (2.9%) (p less than 0.02). Psoriasis is more common in patients with Crohn's disease and their first-degree relatives than in controls, suggesting the possibility of a genetic link. Psoriasis should be included among the extraintestinal manifestations of the condition.

High doses of ranitidine in maintenance therapy of duodenal ulcer patients.

Chronic duodenal ulceration is a recurrent disease. Acute exacerbations may be treated effectively with H2-receptor blockers and a variety of other agents. Intermittent treatment may pose risks of recurrence and complication, and these may be greatly reduced by maintenance treatment. Operative management also reduces recurrence rates, which, however, are commoner in patients coming to surgery nowadays. Full-dose maintenance therapy is an effective option for selected patients.

Single night-time doses of 40 mg famotidine or 800 mg cimetidine in the treatment of duodenal ulcer.

Famotidine (40 mg) and 800 mg cimetidine as single night-time doses were compared in a randomized, double-blind, multicentre study of acute treatment for duodenal ulceration. Fifteen centres recruited 304 patients into the study. Of these, 274 were included for analysis, with 136 receiving famotidine and 138 receiving cimetidine. After 4 weeks, 75% of the patients who received famotidine and 77% of the patients who received cimetidine were healed. At 6 weeks the cumulative healing rates were 91% with famotidine and 87% with cimetidine. Differences between the groups were not significant at 4 or 6 weeks. No significant difference in healing rates between smokers and non-smokers was found. Day and night pain resolved rapidly in both groups. Both treatments were well-tolerated; adverse events were reported in 17 patients on famotidine and 18 on cimetidine, with headache the most frequent event in both groups. Famotidine is effective and well-tolerated in the short-term treatment of duodenal ulcer.

Acute treatment of reflux oesophagitis: a multicentre study to compare 150 mg ranitidine twice daily with 300 mg ranitidine at bedtime.

A randomized, double-blind, clinical trial was undertaken to compare 150 mg ranitidine b.d. with 300 mg ranitidine nocte in the treatment of reflux oesophagitis. Endoscopy data were evaluable for 336 patients after 8 weeks of treatment. At this time 75% of patients who received 150 mg ranitidine b.d., and 73% of those who received 300 mg nocte, had healed or showed endoscopic improvement to grade I oesophagitis. At 12 weeks these rates had increased to 89 and 88%, respectively. Oesophageal biopsies from 258 patients at 8 weeks showed histological improvement in 44 and 47% of those treated with 150 mg ranitidine b.d. and 300 mg ranitidine nocte, respectively. After 12 weeks histological improvement was apparent in 57 and 54% of biopsies from each group, respectively. Symptom severity and frequency was reduced to a similar extent by both treatments. Adverse events were reported by 15 patients. A 300-mg bedtime dose of ranitidine was found to be a well-tolerated, effective alternative to twice daily treatment in reflux oesophagitis.

Enterochromaffin-like cell populations in human fundic mucosa: quantitative studies of their variations with age, sex, and plasma gastrin levels.

The human gastric fundal mucosa contains a variety of endocrine cells, the most numerous of which are the so-called enterochromaffin-like (ECL) cells. We have studied the variations with age and sex of the ECL cell populations, utilizing an assessment based on multiple endoscopic biopsies from four groups of subjects. Plasma gastrin levels were also determined in these subjects. In males, endocrine cell densities declined with age but the ECL cell numbers in females opposed this trend. ECL cell counts showed no appreciable differences between young and old females. In older females, there was a high rate of gastritis and increased levels of circulating gastrin. Concentrations in older females (29.6 +/- 8.7 pmol/l) were higher than in both younger (less than 45 years) males (5.3 +/- 1.1 pmol/l) and older (greater than 55 years) males (6.3 +/- 0.6 pmol/l) (P less than 0.05). The plasma gastrin level was also higher in older females than in young females (13.1 +/- 4.5 pmol/l), although this difference failed to reach statistical significance. In conclusion, clinically silent gastritis, raised gastrin levels, and maintenance or rise of ECL cells numbers, in opposition to a general decrease in endocrine cells with age, appear to be features of women of more than 55 years of age. The variations in ECL cell populations reported here should be taken into account when evaluating possible pathological alterations of the stomach.

Barrett's ulcer: response to standard dose ranitidine, high dose ranitidine, and omeprazole.

Between January 1984 and December 1986, 116 patients were found to have columnar-lined esophagus (Barrett's esophagus) during upper gastrointestinal endoscopy. Twenty-eight patients (16 men and 12 women) were found to have peptic ulcer of the esophagus (Barrett's ulcer). In 17 (60%), standard measures and ranitidine 300 mg daily resulted in healing. Two men with resistant ulcers were treated by surgical repair of their hiatus hernia. Nine (six men, three women) in whom healing failed to occur on this regimen after 3-15 months were treated with high dose ranitidine (300 mg bd). In five, healing was complete after 8 wk and one more healed after an additional 4 wk. The three patients with unhealed ulcers after high dose ranitidine received omeprazole 40 mg in the morning. In two of these, ulcers healed after 4 wk; in the third, one of two ulcers persisted after 8 wk, although the remaining ulcer was smaller and more superficial. Pain relief was good, but minor reflux symptoms persisted in both treatment groups. On completion of the study, patients received 300 mg ranitidine at night. Powerful acid-reducing regimens may be required to heal a proportion of Barrett's ulcers.

A comparison of enprostil and ranitidine in treatment of duodenal ulcer.

Enprostil is a new synthetic prostaglandin E2 with antisecretory and mucosal-protective effects. We compared it with ranitidine in the healing of duodenal ulcer and also examined the subsequent relapse rate. Three hundred thirteen patients were recruited in 15 centers in Europe, of whom 158 were treated with enprostil (E) 35 micrograms twice daily and 155 with ranitidine (R) 150 mg twice daily for up to 6 weeks, using a double-blind method. Patients in both groups were of comparable demography. Healing was significantly quicker with ranitidine. Of patients randomized to treatment, healing (intention-to-treat analysis) at 4 weeks was E 47% and R 69%, and at 6 weeks it was E 66% and R 88%. In patients who met all protocol criteria and completed treatment, healing at 4 weeks was E 58% and R 80%, and at 6 weeks it was E 81% and R 92%. Early relief of pain, both during the day and at night, was significantly quicker with ranitidine. Nausea, diarrhea, vomiting, and abdominal pain occurred more often with enprostil. There were no clinically important abnormalities in hematology or biochemistry. Relapse rates were similar. In conclusion, enprostil is not as effective as ranitidine in healing duodenal ulcers.

A controlled trial of colchicine in primary biliary cirrhosis. Trial design and preliminary report.

Colchicine (1 mg/day), or an identical placebo, was given to 64 patients with primary biliary cirrhosis in a double-blind controlled trial. Due to a novel, pair-matched trial design, the two groups were exceptionally well matched at entry. In comparison with placebo, colchicine produced a beneficial effect on serum albumin and bilirubin levels at 3 months in patients who had abnormal liver function (bilirubin greater than 20 mumol/l) at entry: (albumin, P = 0.047; bilirubin, P = 0.022). In patients with normal liver function at entry (bilirubin less than 20 mumol/l), beneficial effects were noted on total globulin levels at 3 months (P = 0.013) and on immunoglobulin G levels at 3 and 6 months (P = 0.044 and 0.001, respectively). At 18 months, survival estimate in the colchicine and placebo groups were 84% and 69%, respectively. The difference did not reach significance. Colchicine produced an early improvement in liver function and immunoglobulin levels. Few serious side effects were encountered, and colchicine clearly merits long-term study in the treatment of primary biliary cirrhosis.

Crohn's disease of late onset in Blackpool.

Fifty five (26%) of two hundred and fifteen patients presenting with Crohn's disease in the Blackpool area over a 15 year period (1969-1983) were over 60 years of age. There were twice as many women as men (38:17). In 60% disease was limited to the large bowel compared to only 29% in the younger age group. Many of these were women with mild distal colitis. Twenty one patients required operative management. In general, the prognosis was good in colonic disease, but in small bowel and ileocolonic disease the necessity for early operative intervention was potentially fatal. Delayed diagnosis, poor nutritional state and associated disease were relevant adverse factors. The majority of patients at the time of review were well and, where necessary, were coping satisfactorily with a stoma.