Objective assessment of the contribution of each diagnostic test and of the ordering sequence in jaundice caused by pancreatobiliary carcinoma.

BACKGROUND: Computer-assisted diagnostic systems are not substantially more accurate than the clinician in the differential diagnosis of jaundice but may help in optimal selection and sequencing of tests. The present study aimed to assess with an electronic diagnostic tool the pattern of ordering tests and the diagnostic contribution and related financial cost of each test in jaundiced patients with pancreatobiliary carcinoma, in an effort to make the clinician's diagnostic behaviour more efficient and economical. METHODS: Clinical and diagnostic test data were prospectively gathered from 356 jaundiced patients with pancreatobiliary carcinoma and entered in a Bayesian diagnostic programme. The test results were added to the existing diagnostic evidence, and the programme calculated the diagnostic contribution of each test. RESULTS: A total of 1804 diagnostic tests were ordered. Quantitative assessment of the diagnostic contribution of each test showed that percutaneous transhepatic cholangiography and computed tomography were associated with the highest provision of information. The most cost-effective tests were ultrasonography and liver function tests. CONCLUSIONS: It is possible to determine objectively the diagnostic contribution of each test in establishing the diagnosis of pancreatobiliary carcinoma. The observed physician behaviour in ordering the various diagnostic tests might be improved with regard to its efficacy and its cost-effectiveness profile.

Optimum dose of ursodeoxycholic acid in primary biliary cirrhosis.

BACKGROUND: Ursodeoxycholic acid (UDCA) improves liver function tests and prolongs survival in primary biliary cirrhosis (PBC). The dose of 10- 15 mg/kg/day used in the large trials has largely been based on that used for gallstone dissolution. The only dose-response study of UDCA in PBC suggested that a dose of 8 mg/kg/day was the most efficacious. However, disease stage of the patients was not known, higher doses of UDCA were not tried and there was no 'washout period' between the different doses. The aim of this study was to determine the optimum dose of UDCA in early-stage PBC (stage 1 and 2). METHODS: Twenty-four biopsy-proven early-stage PBC patients (one male, 23 female) received five doses of UDCA (0, 300, 600, 900, 1200 mg/day) each for 8 weeks with 4-week washout periods between doses. Symptoms (pruritus, fatigue, diarrhoea) were assessed on a four-point scale (none, mild, moderate, severe). Liver function tests (LFTs) were performed using conventional methods, and serum bile acids were measured using gas liquid chromatography. RESULTS: The dose of 900 mg/day produced the greatest enrichment of UDCA in serum bile acids; although there was no difference in the enrichment of UDCA between the different doses. There was a trend towards normalization of the abnormal LFTs in a dose-dependent manner (for y-glutamyl transferase (yGT), alkaline phosphatase (ALP), alanine transaminase (ALT) and IgM). Multi-factorial analysis showed that UDCA treatment, irrespective of dose, was significantly better than placebo for all the variables. The 900 and 1200 mg doses were better than both 300 and 600 mg using yGT and total bilirubin as variables, better than 300 mg using ALP and IgM as variables, and better than 600 mg using albumin as a variable. No variables showed a significant difference between 900 and 1200 mg. CONCLUSION: The optimum dose of UDCA is 900 mg/day (equivalent to 13.5 mg/kg/day).

Eradication of Helicobacter pylori and prevention of recurrence of duodenal ulcer: a randomized, double-blind, multi-centre trial of omeprazole with or without clarithromycin.

BACKGROUND: Antimicrobial treatment for Helicobacter pylori eradication is currently recommended for all patients with duodenal ulcer disease, but consensus on the best treatment is lacking. METHODS: Patients with active duodenal ulcer and H. pylori were enrolled in a double-blind, randomized, placebo-controlled multi-centre study. Patients received omeprazole 40 mg daily for 28 days and either clarithromycin 500 mg t.d.s. or placebo t.d.s. for the first 14 days. Patients underwent endoscopy before starting treatment, at 2 weeks, immediately after stopping treatment if unhealed at 2 weeks, and at 1, 6 and 12 months after the end of treatment, or at the recurrence of symptoms. Eradication of H. pylori, duodenal ulcer healing and ulcer recurrence were measured. RESULTS: One-hundred and fifty-four patients were recruited and randomized to omeprazole plus clarithromycin (n = 74) or to omeprazole plus placebo (n = 80). One month after treatment, H. pylori was eradicated in 57 of 69 (83%; 95% CI: 72-91%) patients receiving omeprazole plus clarithromycin, compared with 1 of 75 (1%; 95% CI: 0-7%) receiving omeprazole alone (P < 0.001). In patients receiving omeprazole plus clarithromycin the ulcer healed at 2 weeks in 83% (95% CI: 71-91%) and at 4 weeks in 100% (95% CI: 95-100%), compared with 77% (95% CI: 66-86%) and 97% (95% CI: 91-100%) in those given omeprazole plus placebo (N.S.). Ulcers recurred at 12 months in 6% (95% CI: 1-16%) of patients given omeprazole plus clarithromycin, compared with 76% (95% CI: 63-86%) of patients given omeprazole plus placebo (P < 0.001). The incidence of side-effects was similar in both treatment groups (38% with clarithromycin dual therapy and 29% with omeprazole plus placebo; P = 0.304). Ninety per cent of patients took at least 90% of their prescribed medication. CONCLUSIONS: Omeprazole plus clarithromycin dual therapy eradicated H. pylori in 83% of patients with duodenal ulcer and significantly decreased 12-month recurrence from 76% to 6%.

Endoscopic biliary stenting in a district general hospital.

During a 48 month period to December 1990, 367 patients, median age 75 years, with obstructive jaundice caused by common bile duct stones (201), malignant biliary obstruction (148), and benign biliary strictures (18), underwent therapeutic endoscopic retrograde cholangiopancreatography. Endoscopic biliary stenting and drainage was achieved in 343 of 367 patients attempted (93%), seven patients requiring a combined percutaneous endoscopic approach. Endoscopic stenting failed in 24 patients because of malignant duodenal infiltration (10), Billroth 2 gastrectomy (6), tight and extensive biliary strictures (6), peripapillary diverticulum (1), and technical failure (1). Prolonged follow up was available in 91% (311 of 343). The 30 day mortality was 5% (17 of 343), which included two procedure related deaths (0.6%) from fulminant pancreatitis and major sphincterotomy site bleeding. Early complications occurred in 14% (48 of 343) and late complications occurred in 11.9% (35 of 294) patients, as of the original 343, 17 had died within 30 days and another 32 were lost to follow up. Eighty patients with incomplete bile duct clearance and eight patients with benign biliary strictures had biliary stents inserted for 12-48 months (median 30). Endoscopic biliary stenting services are necessary in a district general hospital with technical success, death and morbidity rates comparable to other studies.

A comparison of omeprazole and ranitidine in the prevention of recurrence of benign esophageal stricture. Restore Investigator Group.

BACKGROUND/AIMS: Dilatation combined with subsequent pharmacological control of gastroesophageal reflux represents a logical but poorly documented approach to the management of benign esophageal stricture. This large trial (366 patients) aimed to assess whether omeprazole as the most effective available medication for gastroesophageal reflux disease prevents recurrent stricture formation. METHODS: Patients (n = 366) were randomized in a double-blind study to undergo either omeprazole (20 mg once daily; 180 evaluable patients) or ranitidine therapy (150 mg twice daily; 185 evaluable patients) for 1 year after dilatation to 12-18-mm diameter (36-54F gauge). Subsequently, endoscopy and dilatation were performed when clinically indicated and endoscopy on completion. Symptoms were assessed at clinic visits every 3 months and using weekly diary cards. RESULTS: Fewer patients undergoing omeprazole therapy required redilatation compared with those on ranitidine (43 of 143 [30%] vs. 66 of 143 [46%] by 12 months; P < 0.01), and patients in the omeprazole group needed fewer redilatations during the year (0.48 vs. 1.08; P < 0.01). On completion, symptom relief favored omeprazole: 76% of patients in the omeprazole group were free of dysphagia (compared with 64% in the ranitidine group; P < 0.05); 83% were able to accept a normal diet (69%; P < 0.01); and 65% were completely asymptomatic (43%; P < 0.001). CONCLUSIONS: Omeprazole, 20 mg once daily, was more effective than ranitidine, 150 mg twice daily, as prophylaxis against stricture recurrence and in providing symptom relief.

Observer variation and discriminatory value of biopsy features in inflammatory bowel disease.

If skilled histopathologists disagree over the same biopsy specimen, at least one must have an incorrect interpretation. Thus, disagreement is associated with, although not the cause of, diagnostic error. The present study aimed to determine the magnitude of variation among 10 observers with a special interest in gastrointestinal histopathology. They independently interpreted the same biopsy specimens for morphological features which may discriminate between patients with Crohn's disease and ulcerative colitis and normal subjects. Thirty of 41 features had agreement measures significantly better than expected by chance (p < 0.05). The range of agreement in the 45 observer pairs over the final diagnosis was 65-76%. There was good agreement in discriminating between normal slides and those showing confirmed inflammatory bowel disease. For normal slides, however, the term nonspecific inflammation was often applied and without any consistency. In addition, true Crohn's disease slides were often and consistently thought to be ulcerative colitis. Having identified 11 important discriminatory morphological features, two multiple regression analyses were then carried out to produce a scoring system for inflammatory bowel disease. These results suggest there is considerable room for improvement in the reliability of colonic biopsy specimen interpretation and that this could probably be achieved using more exact definitions of morphological features and diseases.

Composite glandular-carcinoid tumour of the terminal ileum.

AIMS: To investigate a female patient with a tumour mass of the terminal ileum, to define the nature of the tumour, and to correlate its morphology and behaviour with similar types of tumours of the large intestine and stomach. METHODS: Tissues obtained at colonoscopy, from hemicolectomy specimens, and from liver and peritoneal biopsy specimens were studied macroscopically, microscopically, histochemically, and immunohistochemically for epithelial membrane antigen (EMA), carcinoembryonic antigen (CEA), neuron specific enolase (NSE), and S100 protein. RESULTS: Macroscopic examination showed a tumour of the terminal ileum protruding into the caecum. Microscopically the tumour showed two components, one adenoma with moderate dysplasia and the other carcinoid tumour. The adenomatous component stained positively for EMA and CEA and negatively for NSE. The carcinoid component stained positively for NSE and negatively for EMA and CEA. Histochemically the carcinoid area was argyrophil positive and argentaffin negative. Only the carcinoid had metastasised, to the liver, peritoneum, and the lymph nodes, at the time of diagnosis. CONCLUSION: The morphological, histochemical, and immunohistochemical findings confirm the diagnosis of a composite adenoma-carcinoid tumour of the terminal ileum.

Chronic periaortitis presenting as common bile duct obstruction.

The case of a 67 year old woman is reported who presented with cholestatic jaundice and was found to have, in addition, an inflammatory abdominal aortic aneurysm. Only at necropsy did histopathology show chronic periaortitis as the aetiology of a pancreatic head mass which, during life, mimicked a pancreatic neoplasm obstructing the bile and pancreatic ducts.

Use of a modified angioplasty balloon catheter in the dilatation of tight biliary strictures.

Nineteen biliary strictures were dilated using a modified angioplasty balloon catheter to allow insertion of a 10F prosthesis. In each instance biliary strictures were successfully dilated which had previously been too tight to widen with standard endoscopic biliary dilating catheters. Eleven patients had malignant hilar strictures, four malignant distal common bile duct strictures, and four benign strictures. There were no complications as a result of the procedure and satisfactory biliary drainage was established in all patients. We conclude that tight biliary strictures can be successfully dilated using a modified angioplasty balloon catheter.

Doctors' attitudes to risk in difficult clinical decisions: application of decision analysis in hepatobiliary disease.

Twelve doctors with special training in hepatology independently reviewed two to five cases each from a group of seven cases of complicated hepatobiliary problems. A doctor's willingness to take risks to improve his patients' health was quantified by a wagering technique based on the probability of achieving a successful intervention. These probabilities were then used to calculate "utilities," which represented the average opinion of the doctors about the relative worth of each of six predefined states of health. The results showed that, in the context of risky decisions for severely ill patients, a year of life was considered by the doctors to be worth 44% of a full recovery; being mobile for that year increased this value to 57%. Survival for up to five years with restricted mobility was considered to be worth 70% of a full recovery and the ability to work during that period increased this value to 85%. It is concluded that in clinical decision making the uncertainty and preferences implicit in a course of action can be quantified and thus made explicit.

The value of clinical, biochemical, ultrasound and liver biopsy data in assessing patients with liver disease.

To determine the value of clinical, biochemical, ultrasound and liver biopsy data in the management of patients with liver disease, eight doctors each assessed 75 case histories. With clinical and biochemical data alone, the predictive accuracy was significantly higher when identifying patients as 'medical' rather than 'surgical' (97 compared with 79%, p less than 0.001). However, when making a specific diagnosis as opposed to classifying into medical and surgical categories, clinical and biochemical information resulted in a much lower predictive accuracy for both medical (67%) and surgical (56%) patients. With ultrasound data the predictive accuracy increased to 91% when identifying patients as 'surgical'; with liver biopsy it increased to 99% when identifying patients as 'medical'. The value of the different data assessed involves more than an evaluation of diagnostic accuracy, and in this study the relative worth of each test was therefore assessed on a five point scale based on the effect of the information on the doctors. This included a willingness to give specific treatment and make a specific diagnosis, as well as classifying patients into medical and surgical categories and the confidence they felt in their diagnoses. After clinical, biochemical and ultrasound information the doctors were only prepared to give specific treatment to 11.9% of the medical and 9.3% of the surgical patients. After liver biopsy data, however, they were willing to give specific treatment to an additional 66.6% of the medical patients and 25% of the surgical patients. Further evidence of the value of liver biopsy information came from an analysis of the changes in the doctors' confidence in a diagnosis. Thus, 96 patients were assigned a correct specific diagnosis with clinical and biochemical data alone but none were considered as 'definitive' by the doctors; when liver biopsy information was provided 59 (61%) were placed in this category.

A prospective randomized study of two sclerotherapy techniques for esophageal varices.

In a study designed to compare the efficacy and safety of two techniques of injection sclerotherapy, 40 patients (30 with cirrhosis and 10 with portal vein block) were randomly allocated to the sheath or free-hand technique. Although the former was associated with significantly less bleeding within the first 24 hr of injection (p less than 0.05) but more postinjection pain (p less than 0.05) and esophageal stricture, there was a trend toward earlier obliteration of varices. This was most marked over the first three courses of injection, and although frequency of rebleeding was not significantly less, none of the 11 episodes in the sheath group were fatal, compared to 5 of 15 bleeds in those injected by the free-hand technique (p less than 0.05).

Controlled trial of methylprednisolone therapy in severe acute alcoholic hepatitis.

The efficacy of methylprednisolone (1 g daily or three days), which is effective in reversing transplant rejection, was assessed in a randomised controlled trial of 55 patients with severe acute alcoholic hepatitis, 34 of whom had encephalopathy. The clinical progress, frequency of bleeding and sepsis, and cause of death were similar in the treatment (27 patients) and control groups (28 patients). There was no significant difference in mortality rate between the two groups: 57% of the control group and 63% of the treatment group died during the study. Patients' survival depended on the presence of absence of the following features: encephalopathy, serum bilirubin concentration more than 340 micromol/l, serum creatinine concentration more than 250 micromol/l, and histological evidence of cirrhosis as well as severe acute alcoholic hepatitis.

Increased long-term survival in variceal haemorrhage using injection sclerotherapy. Results of a controlled trial.

Analysis of 107 patients with cirrhosis and recent variceal haemorrhage included in a prospective randomised trial of endoscopic injection sclerotherapy showed that in the sclerotherapy group 22 (43%) of the 51 patients had episodes of haemorrhage during the period of treatment, but in only 4 did bleeding occur after the varices had been obliterated. This contrasts with episodes of bleeding in 42 (75%) of the 56 patients receiving standard medical management-a highly significant difference. The overall risk of bleeding per patient-month of follow-up was reduced threefold with sclerotherapy. Of 22 patients followed up for at least one year after obliteration of varices, 14 had no evidence of reappearance of varices within this period and, by means of cumulative life-analysis tables, survival was shown to be significantly improved in the sclerotherapy group.

Reactivation of hepatitis B virus infection in two patients: immunofluorescence studies of liver tissue.

Two patients, 1 with chronic active hepatitis, the other with Goodpasture's syndrome, became HBsAg-positive after the start of immunosuppressive drug therapy. At the same time of presentation, sera contained anti-HBc antibodies of IgM and IgG class in the absence of HBsAg or anti-HBs and immunofluorescent studies of liver biopsy specimens showed core antigen in the nuclei of liver cells. It is suggested that these findings reflected an unusual pattern of hepatitis B virus infection with a very low level of viral replication and that the appearance of HBsAg in both serum and liver cells after immunosuppressive drug therapy was due to reactivation of this infection, possibly as a result of changes in levels of antibodies which suppress viral replication. In 1 patients, the change in viral replication was associated with continuing liver cell necrosis and progressive deterioration in liver function.

Inter-observer variation of symptoms and signs in jaundice.

Five observers each examined 20 jaundiced patients, recording clinical signs and symptoms on a form which also gave the definitions used for the study. The balanced design of the study allowed examination for order effects, but none were found, except for a tendency for agreement on indicants with more than two categories to improve as the study progressed. Chance agreement was corrected by the use of kappa statistics which showed that 80% of the indicants showed agreement significantly greater than expected by chance. Certain indicants (dark urine, variability of jaundice, abdominal pain, character of liver edge and presence of spleen) showed no evidence of significant agreement, even though the indicants were frequently observed in both states - present or absent. The percentage of correct clinical diagnoses reached by the observers (without biochemical or any other information) varied between 65% and 84%. The consensus diagnosis was correct in 80% of cases. Agreement was higher if the diagnosis was simplified to a 'Medical' or 'Surgical' diagnosis, the observers' accuracy being between 90 and 100%.