Non-responders to hepatitis B vaccination: a review.

Hepatitis B virus (HBV) infection is a major public health issue throughout the world and vaccination of those at risk is the main method of containment. Of healthy vaccinees, 5-10% fail to mount an adequate antibody response. The antibody levels of an unknown further fraction of vaccinees fall considerably over time rendering them at a potential risk of infection. The scope of this article is to review the factors that might influence the immune response to HBV vaccination, to review the methods used to overcome the problem of poor response and to discuss what possible guidelines are available or needed in treating these vaccinees.

Update in the pharmacological management of peptic ulcer haemorrhage.

The management of peptic ulcer haemorrhage still poses questions and controversies and this applies to the pharmacological mode. This review suggests that high-dose acid suppression is beneficial in reducing rebleeding and surgery rates. The choice of acid suppressant is far from conclusive, but emerging evidence suggests that proton pump inhibitors may be more effective than H2-antagonists. The only other drug which may be useful in selected patients is octreotide, but its universal use cannot be recommended.

Acid suppression in peptic ulcer haemorrhage: a 'meta-analysis'.

BACKGROUND: The use of acid-decreasing agents in the management of peptic ulcer haemorrhage continues to be controversial. Most clinical trials examining the efficacy of these drugs contain small numbers of patients, making it difficult to draw conclusions about their efficacy. METHODS: We report a meta-analysis that examined the effect of these drugs in the management of peptic ulcer haemorrhage. Included studies were located using a search of the Medline database between 1980 and 1999. Studies were published in English, randomized and controlled by a placebo group. Mantel-Haenszel and blinded random models were used in conducting the statistical processing of this meta-analysis. RESULTS: Twenty-one randomized placebo-controlled trials were included. The total number of patients was 3566 and the mean study size was 170 (range 20-1005). Seventeen of the papers assessed the efficacy of H2-antagonists, three assessed proton pump inhibitors and one was concerned with antacid therapy. The meta-analysis showed a significant reduction in re-bleeding rates (odds ratio, OR 0.727, 0.618-0.855, P < 0.001) and surgery rates (OR 0.707, 0.582-0.859, P < 0.001) when acid decreasing agents are used for acute peptic ulcer haemorrhage. Mortality rates appear to be unaffected (OR 1.140, 0.818-1.588, P=0. 49). CONCLUSIONS: This meta-analysis demonstrates a significant beneficial effect of acid-decreasing agents in lowering re-bleeding and surgery rates, but demonstrated no effect upon mortality.

An update in the palliative management of malignant dysphagia.

BACKGROUND: Oesophageal cancer is generally associated with late presentation and poor prognosis. Therefore palliative surgery has been largely superseded by less invasive non-surgical techniques. Once palliation is indicated, the aims of the management should be: the maintenance of oral intake, minimizing hospital stay, relief of pain, elimination of reflux and regurgitation and the prevention of aspiration. METHODS: This study was a review of all published English language data on the palliation of malignant dysphagia between 1994-1999. The Medline and Bids databases were searched and other references were derived from the material perused. RESULTS AND CONCLUSIONS: Palliative treatment for oesophageal cancer should be individualized and relate to tumour stage, size and location, the patient's medical condition and his/her personal wishes. The palliative treatment largely includes self-expanding metal stents (SEMS), laser (including photodynamic therapy (PDT)) or a combination of the two to relieve symptoms, this may be employed with or without other treatments such as radiotherapy/chemotherapy (RT/CT) with the aim of reducing tumour bulk and possibly prolonging survival. A multi-disciplinary approach is vital in patients with advanced oesophageal cancer.

Non steroidal anti-inflammatory drugs and colorectal cancer: is there a way forward?

Non steroidal anti-inflammatory drugs (NSAIDs) have diverse clinical applications through modulation of oxidative processes and cell signalling. Observations that these agents may inhibit human colorectal carcinogenesis have produced great excitement. However, comparative data relating to their chemopreventative effectiveness or to relevant mechanisms of action remains unclear. This review considers the clinical and epidemiological evidence for colorectal tumour prevention by NSAIDs against current concepts of drug mechanisms. We also propose areas of further research for potential therapeutic advancement.

Role of p53 assessment in management of Barrett's esophagus.

The risk of developing gastroesophageal adenocarcinoma is increased in patients with Barrett's esophagus. The management of dysplasia in Barrett's esophagus remains controversial. Understanding of the sequence of events preceding malignancy is essential before screening protocols for early diagnosis and preventive measures can be implemented. The aim of this review is to examine the published data on the role p53 assessment may play in the management of Barrett's esophagus. Relevant papers were identified by an extensive text word search of the Medline database and a review of quoted articles. The p53 abnormality occurs more frequently in highly dysplastic epithelium than in nondysplastic epithelium. However, the retrospective nature of most of the available data could be a significant confounding factor. Our current knowledge suggests that p53 protein overexpression does not seem to predict future progression to cancer or determine disease outcome. The p53 abnormality alone can not be reliably used to predict progression of Barrett's esophagus to cancer. We must await long-term evaluation of patients to determine the percentage of patients with p53 gene abnormality, and nondysplastic Barrett's who will progress to dysplasia or carcinoma. Large randomized controlled long-term follow-up studies are much needed.

The effect of octreotide on gastroduodenal blood flow measured by laser Doppler flowmetry in rabbits and man.

OBJECTIVE: The somatostatin analogue, octreotide is valuable in the management of variceal bleeding, and it has been suggested that it may stop peptic ulcer hemorrhage by reducing gastroduodenal blood flow or increasing intragastric pH. The aim of this study was to determine the effect of intravenous octreotide infusion on gastroduodenal mucosal blood flow and gastric pH. METHODS: Seven New Zealand white rabbits and five healthy human volunteers were used. Mucosal blood flow was measured using a laser Doppler flowmeter (LDF). The Doppler probe was positioned in the upper gastrointestinal tract of the seven rabbits and five human volunteers. Blood flow was measured before and after octreotide infusion. RESULTS: In the animal experiments, mucosal blood flow was decreased in a dose dependent manner in the gastric body (209.1-56.3 U) (p < 0.008), antrum (143.3-33.3 U) (p < 0.02) and duodenum (254-67.6 U) (p < 0.016) by doses of octreotide ranging from 10-50 microg/kg of body weight. In the human studies, mucosal blood flow was decreased in the gastric body (p < 0.016) and antrum (p < 0.009) after octreotide infusion (dose 1-1.5 microg/kg). Intragastric pH was significantly increased (p < 0.05). The change was not associated with systemic hemodynamic changes. CONCLUSIONS: Gastroduodenal mucosal blood flow was reduced and intragastric pH increased by octreotide. This agent could be helpful in the management of gastroduodenal mucosal bleeding.

Role of photodynamic therapy in the management of gastrointestinal cancer.

BACKGROUND: Surgery for cancer of the gastrointestinal tract is associated with high morbidity and mortality, especially in older patients. A significant proportion of patients cannot be cured and would be referred for palliative therapy. Others may have early cancer but are deemed unfit for surgery. Chemotherapy and external radiotherapy are suitable for only a proportion of patients. Therefore, photodynamic therapy may have a role in the management of these patients. It was the possibility of achieving selective tumour necrosis with sparing of normal tissue that made this treatment extremely appealing compared to other conventional tumour therapy. METHOD: The literature is reviewed (after an extensive Medline search 1975-1997) regarding the scientific basis of photodynamic therapy and the clinical experience to date with this therapy in the management of malignancies of the gastrointestinal tract. RESULTS AND CONCLUSIONS: Photodynamic therapy holds the promise of an eradication form of treatment for early cancer especially for patients deemed unfit for other treatment. It may also prove a useful supplement to other techniques in order to eliminate small residual areas of tumour left after the main bulk has been removed by other methods. The use of photodynamic therapy in the palliative management of gastrointestinal tract cancer is likely to be limited.

Appendicectomy and ulcerative colitis.

The aetiology of ulcerative colitis (UC) is unknown. However, much interest has been devoted recently to the relationship between appendicectomy and ulcerative colitis. A case-control study was conducted, comparing appendicectomy rates between 110 patients with UC (group 1) and 136 patients attending an orthopaedic clinic free from UC (group 2). The appendicectomy rates were 0.9% (group 1) and 10.3% (group 2), respectively (P < 0.002). The present study shows that patients with ulcerative colitis had rarely undergone appendicectomy before the first manifestation of colitis. Further research on this relationship is called for.

Gastric cancer distal to the cardia--prevention or cure?

Adenocarcinoma of the stomach distal to the cardia remains one of the most common cancers in the world. The interest in the aetiology of this disease has been rekindled because of recent epidemiological and molecular studies linking this cancer to H. pylori and certain dietary factors. The authors provide an updated review of the aetiology of gastric cancer. This review seeks to summarize the disease, to propose pathways of carcinogenesis and to suggest ways in which the "traditional" risk factors may be interpreted on the basis of evolving knowledge.

Experimental studies of injection therapy for ulcer haemorrhage in rabbits.

BACKGROUND: Endoscopic injection therapy is a well established method of controlling peptic ulcer haemorrhage but the optimum injection solution and the mechanism involved in inducing haemostasis are unknown. METHODS: The efficacy and effects on tissue of various therapeutic agents used in the control of gastric mucosal haemorrhage were studied in ten rabbits. Thirty-eight bleeding mucosal ulcers (blood loss above 1.5 ml/min) created at gastrotomy were studied. Adrenaline (1:100,000), thrombin, fibrin (thrombin plus fibrinogen), 5 per cent ethanolamine and 50 per cent dextrose were injected; a fibrin suspension was also sprayed around bleeding ulcers. RESULTS: Sclerosants were found to be least effective in the control of bleeding and were associated with significant tissue necrosis. Although all the other solutions significantly decreased blood loss within 30 min of injection (median blood loss 0.25 ml/min), only an injected mixture of adrenaline plus thrombin and sprayed fibrin achieved complete haemostasis within 2 min of treatment and with no recurrence of bleeding. Neither agent caused significant tissue damage. Histological examination showed that no solution caused arterial thrombosis when injected next to a major ear artery. CONCLUSION: Sclerosants caused extensive tissue necrosis and were least effective in the control of ulcer haemorrhage. A combination of dilute adrenaline and human thrombin may represent optimal haemostatic therapy for peptic ulcer haemorrhage.

Reduced long-term survival following major peptic ulcer haemorrhage.

BACKGROUND: The late outcome of patients who present with major peptic ulcer haemorrhage is unclear. An examination was made of the hypothesis that prognosis may be poor because many such patients have severe co-morbid diseases. METHODS: Some 121 patients treated endoscopically for severe peptic ulcer haemorrhage were followed for a median of 36 (range 30-76) months and outcome was compared with that of age- and sex-matched controls. RESULTS: Thirty patients (25 per cent) died during the follow-up period and Kaplan-Meier plots showed reduced survival in patients with ulcers (P < 0.01). Death was restricted largely to patients who had co-morbid diseases. Eight of the remaining 91 patients had further peptic ulcer bleeding; two of these were taking maintenance acid-reducing therapy and only one had significant dyspepsia before rebleeding. Eighty-three per cent of surviving patients had little or no dyspepsia. CONCLUSIONS: The late prognosis of patients who present with major ulcer haemorrhage is poor, but most deaths are a consequence of co-morbid disease and not recurrent ulcer bleeding. Most patients have little dyspepsia and those who rebleed are largely free from dyspepsia.

The outcome of urgent surgery for major peptic ulcer haemorrhage following failed endoscopic therapy.

OBJECTIVE: To review the outcome of patients who underwent emergency surgery for major peptic ulcer haemorrhage after failed endoscopic therapy. To address whether 'conservative' or 'aggressive' surgery is best. DESIGN: A retrospective analysis of emergency surgery for ulcer bleeding which could not be controlled by endoscopic therapy. SETTING: The four admitting units in the Lothian region of Scotland. PARTICIPANTS: Sixty-seven patients who failed endoscopic therapy for bleeding peptic ulcer and underwent emergency surgery between December 1990 and December 1995. Simple underrunning or excision of ulcer alone was done in 31 patients whilst 36 had more radical surgery. MAIN OUTCOME MEASURES: Rebleeding and 30-day mortality rates. RESULTS: Rebleeding was significantly higher in patients treated by underrunning (7 versus 1, P < 0.013). There were fewer deaths in the radically treated group (5 versus 7, not significant). CONCLUSION: Patients undergoing surgical operation for severe peptic ulcer haemorrhage after failed endoscopic therapy may be best served by a relatively aggressive approach.

Upper gastro-intestinal disease in Scotland: a survey of practice amongst Scottish gastroenterologists.

Given the range of causes of upper gastrointestinal disease (UGD), the evolving role of Helicobacter pylori in its pathogenesis and the variety of treatments available, one might expect complex management strategies in the management of these diseases. The aim of this study was to determine the current management strategies used in peptic ulcer disease and gastritis in Scotland and to identify areas where large and clinically important variations in practice exist between gastro-intestinal specialists. Between June and September 1994, 130 gastro-intestinal physicians and surgeons were sent a postal questionnaire based on their response to four hypothetical clinical scenarios. Eighty-one (63%) correspondents returned completed questionnaires. The case histories related to: bleeding duodenal ulcer; peptic ulceration whilst taking non-steroidal anti-inflammatory drugs (NSAIDs) and corticosteroids; management of dyspepsia in the young; and management of gastritis. Thirty-eight per cent of clinicians surveyed advocated the use of intravenous acid reducing agents in peptic ulcer bleeding. A total of 88% advocated endoscopic therapy in the presence of stigmata of recent haemorrhage and 5% suggested a follow up of endoscopy to confirm healing after ulcer bleeding. In treating the patient with ulcer while on NSAIDs, 45% of clinicians would use H2 receptor antagonists, 37% would use omeprazole, 14% misoprostol and 4% helicobacter eradication. Of the clinicians surveyed, 63% said they would investigate a 25-year-old patient with dyspepsia by endoscopy and 84% of these will biopsy for H. pylori. Empirical treatment was favoured by 37% and 4% considered a barium meal. There was no consensus in the treatment of gastritis. There exists considerable divergence of opinion between clinicians in investigation and treatment of upper gastrointestinal disease. The role of endoscopy, the type and duration of medical treatment of bleeding and non bleeding ulcer and gastritis require further, more detailed investigation. A consensus document would be warmly welcomed.