W. M. Hui

Soluble E-cadherin is a valid prognostic marker in gastric carcinoma

BACKGROUND Gastric cancer remains a major cause of cancer mortality globally but no good prognostic tumour marker is available. Soluble fragment of E-cadherin protein has been reported to increase in the sera of patients with cancer and recently was found to be elevated in 67% of patients with gastric cancer. AIMS To investigate if serum soluble E-cadherin is a valid prognostic marker in gastric cancer. METHODS Concentrations of soluble E-cadherin from 116 patients with histologically confirmed gastric adenocarinoma and 40 healthy subjects were measured using an immunoenzymometric method with a commercially available sandwich ELISA kit based on monoclonal antibodies. RESULTS The logarithm of the means of soluble E-cadherin concentration was significantly higher in patients with gastric cancers (mean 3.85 (SD 0.28)) than in healthy subjects (3.71 (0.18)) (p=0.001), and in palliative/conservatively treated cancers (3.91 (0.35)) than in operable cancers (3.78 (0.19)) (p=0.015). The logarithm of the concentrations correlated with tumour size (p=0.032) and carcinoembryonic antigen concentrations (p=0.001). The cut off value calculated from discriminant analysis on operability and inoperability/palliative treatment was 7025 ng/ml. Soluble E-cadherin concentrations higher than this cut off value predicted tumour (T4) depth invasion (p=0.020, confidence interval (CI) 1.008–1.668) and palliative/conservative treatment (p=0.023, CI 1.038–2.514). In contrast, the relative risks for lymph node (N2) metastasis, distant metastasis, and stage III/IV disease were 1.41, 1.33, and 1.55 respectively, despite not reaching statistical significance. CONCLUSION Serum soluble E-cadherin is a potential valid prognostic marker for gastric cancer. A high concentration predicts palliative/conservative treatment and T4 invasion.

EFFECT OF OMEPRAZOLE ON DUODENAL ULCER-ASSOCIATED ANTRAL GASTRITIS AND HELICOBACTER PYLORI

This study set out to investigate the effects of omeprazole or ranitidine on the progression of antral gastritis andHelicobacter pylori in patients with active duodenal ulcer. A double-blind, double-dummy trial was performed in 270 patients, 241 of whom were studied histologically for the presence ofH. pylori. Patients were randomized to receive omeprazole, 10 mg every morning, omeprazole, 20 mg every morning, or ranitidine, 150 mg twice a day, for four weeks. Endoscopy was performed on entry and at weekly intervals during the study; at least two antral biopsies were taken on each occasion to assess the activity and degree of chronic inflammation, as reflected by the degree of polymorphonuclear leukocyte infiltration and mononuclear cell infiltration, respectively. Biopsy specimes also were assessed histologically forH. pylori. The sex, age and maximal acid output were comparable in the three treatment groups. The percentages of patients showing an improvement in the activity of gastritis in the four consecutive weeks of treatment were 9%, 40%, 51%, and 53% for omeprazole, 10 mg (N=78); 14%, 42%, 49%, and 53% for omprazole, 20 mg (N=81); and 2%, 23%, 30%, and 33% for ranitidine, 150 mg twice a day (N=82) (life table analysis gaveP<0.01 for both omeprazole regimens compared with ranitidine). The degree of chronic inflammation showed similar changes. The density ofH. pylori decreased significantly after treatment with omeprazole, 10 mg or 20 mg, (both,P<0.00001) but not with ranitidine. The reduction in bacterial density was significantly higher (P<0.003) in those who showed improvement of gastritis than in those who did not. We conclude that effective acid inhibition with omeprazole improves antral gastritis and is accompanied by a reduction in antral bacterial density, suggesting that both acid andH. pylori may be involved in the pathogenesis of antral gastritis.

Sucralfate Overcomes Adverse Effect of Cigarette Smoking on Duodenal Ulcer Healing and Prolongs Subsequent Remission

A unicenter, single-blind, randomized study was conducted on 283 patients with active duodenal ulcer to compare possible factors that may affect healing and relapse in patients treated with a potent antisecretory agent, cimetidine, or a site-protective and cytoprotective agent, sucralfate. The endoscopic healing rates at 4 wk were 76% and 79%, respectively, and cross-over treatment of the failures for a further 4 wk resulted in 68% healing with cimetidine and 69% healing with sucralfate, both differences being not statistically different. Unlike cimetidine, healing by sucralfate was unaffected by cigarette smoking, reluctance to give up smoking, habitual use of alcohol, high maximal acid output, and large ulcer diameter. In particular, the healing rate of smokers treated with sucralfate (82%) was significantly greater than that of smokers treated with cimetidine (63%). Duodenal bulb deformity significantly affected healing in both groups, and was the only offsetting factor identifiable for sucralfate out of 46 factors examined. Of the patients with healed ulcers, 238 participated in a 24-mo follow-up study consisting of interviews at 2-mo intervals and endoscopy at 4-mo intervals or whenever symptoms recurred. The cumulative relapse rate was significantly (p less than 0.007) greater in patients healed with cimetidine than with sucralfate, 50% relapse occurring at 6 and 12 mo, respectively. In both, the cumulative relapse rate was significantly greater in cigarette smokers than in nonsmokers, but smokers and nonsmokers treated with cimetidine relapsed (50% at 4 and 8 mo, respectively) faster than the corresponding smokers and nonsmokers treated with sucralfate (50% at 8 and 18 mo, respectively). Furthermore, in cimetidine- but not sucralfate-healed patients, early ulcer relapse (within 6 mo) was associated with short duration of illness, short remission period, long symptomatic spell, and reluctance to give up smoking. We conclude that smoking adversely affects duodenal ulcer healing by cimetidine and hastens subsequent relapse, and that sucralfate overcomes the adverse effect of smoking on healing as encountered with cimetidine, and results in a subsequent remission period double that of cimetidine.

Randomised crossover trial of tripotassium dicitrato bismuthate versus high dose cimetidine for duodenal ulcers resistant to standard dose of cimetidine.

Of 212 patients with duodenal ulcer treated with four weeks of one gram daily cimetidine, 25 had ulcers which underwent no reduction in size despite treatment. The effects of tripotassium dicitrato bismuthate (TDB) tablet four times a day or cimetidine 1.6 g daily on the healing of these cimetidine resistant ulcers were compared in a randomised crossover trial. Ten of 12 patients on tripotassium dicitrato bismuthate and five of 13 patients on high dose cimetidine had complete healing (p less than 0.02). On crossing over, seven of the eight ulcers not healed by high dose cimetidine completely healed with TDB in another four weeks, and one of the two ulcers not healed by TDB healed with high dose cimetidine. Overall, TDB healed 85% of cimetidine resistant ulcers, whereas high dose cimetidine healed 40% (p less than 0.006). Tripotassium dicitrato bismuthate is recommended for cimetidine resistant duodenal ulcers.

A RANDOMIZED COMPARATIVE STUDY OF LASER PHOTOCOAGULATION, HEATER PROBE, AND BIPOLAR ELECTROCOAGULATION IN THE TREATMENT OF ACTIVELY BLEEDING ULCERS

A randomized study was performed to compare the efficacy of Nd:YAG laser, heater probe, and bipolar electrocoagulation in the treatment of active bleeding from peptic ulcers. Nine hundred and forty-eight consecutive patients with upper gastrointestinal bleeding underwent endoscopy and 91 patients with active bleeding from peptic ulcer were randomized to receive laser (N = 30), heater probe (N = 31), and bipolar electrocoagulation (N = 30). The angulation of the probe to the ulcer base was assessed at endoscopy. The three treatment groups were comparable in their clinical and endoscopic characteristics. There was no significant difference among patients treated with laser, heater probe, and bipolar electrocoagulation in the rate of re-bleeding (10%, 19.4%, and 10%), duration of hospital stay (4, 4, and 5 days), and proportion requiring emergency surgery (7%, 13%, and 7%), but the cost per patient was higher with laser than heater probe and bipolar electrocoagulation. The angulation of the probe to the ulcer base did not affect the re-bleeding rate. No complication was reported. We conclude that the three modalities were equally effective and safe in endoscopic hemostasis but because bipolar electrocoagulation and heater probe were cheaper, they were recommended for use.

Efficacy of sucralfate in corpus, prepyloric, and duodenal ulcer-associated gastric ulcers: A double-blind, placebo-controlled study☆

A 12-week study with two weekly endoscopic assessments was performed in 138 patients to compare the efficacy of sucralfate fine granules (900 mg one-half hour before breakfast, lunch, and dinner, and at bedtime) versus placebo in the healing of gastric ulcers prestratified into corpus, prepyloric, and duodenal ulcer-associated. For corpus and prepyloric ulcers, the respective healing rates achieved by sucralfate at six weeks (69 and 80 percent) and at eight weeks (80 and 93 percent) were significantly (p less than 0.005) better than those obtained with placebo (33 and 25 percent at six weeks, and 41 and 33 percent at eight weeks). The design of the study permitted life-table analysis that further demonstrated the efficacy of sucralfate in these two ulcer types (p less than 0.0001). Symptomatic response was likewise significantly better with sucralfate than with placebo. Similar healing rates and symptomatic responses were observed for patients with duodenal ulcer-associated gastric ulcer but were not significantly better with sucralfate than with placebo. From 38 prospectively obtained clinical, personal, physiologic, and endoscopic characteristics, it was found that ulcer size and a history of pain had significant influence on healing with sucralfate. It is concluded that sucralfate is safe and effective for the treatment of corpus and prepyloric ulcers.

Subclinical hepatocellular carcinoma in Hong Kong Chinese.

Of the 208 Chinese patients with histologically proven hepatocellular carcinoma (HCC) seen during a 5-year period, 191 patients presented with symptomatic HCC and 17 patients with asymptomatic HCC (subclinical HCC, SCHCC) being picked up by alpha-fetoprotein (AFP) screening. Compared with the patients with symptomatic HCC, patients with SCHCC had a better performance status (p less than 0.01), higher serum albumin levels (p less than 0.05) and lower alkaline phosphatase levels (p less than 0.01). In those patients with symptomatic HCC, 4.7% were operable and only 2 patients had a tumour diameter of less than 5 cm. In contrast, patients with SCHCC had a higher operability rate (76.5%, p less than 0.0001) and all had a tumour of less than 5 cm in diameter (p less than 0.0001). Patients with SCHCC, most of whom had their tumour resected, had a better long-term survival (p less than 0.0001). We conclude that patients with SCHCC picked up by AFP serosurveillance have a better performance status, higher operability and better prognosis.

The influence of acute or chronic nicotine treatment on ethanol-induced gastric mucosal damage in rats

The influences of acute or chronic nicotine pretreatment on ethanol-induced changes on gastric secretion, mucosal blood flow (GMBF), and glandular mucosal damage were studied in anesthetized rats. Ethanol administration decreased gastric acid secretion and GMBF, which were accompanied by a marked increase in gastric mucosal damage. Acute nicotine incubation 2 or 4 mg dose-dependently elevated both the titratable acid in the luminal solution and the gastric secretory volume; it also prevented the depressive action on GMBF and gastric mucosal damage in ethanol-treated animals. Chronic nicotine treatment for 10 days reduced the inhibitory action of ethanol on gastric acid secretion; the higher dose (25 μg/ml drinking water) potentiated the decrease of GMBF and the ulcerogenic property of ethanol. However, chronic treatment with the lower dose (5 μg/ml drinking water) had the opposite effects; it also markedly increased the gastric secretory volume. It is concluded that acute nicotine pretreatment elevates, whereas chronic nicotine pretreatment differentially affects GMBF. These effects could account for their protective or preventive actions on ethanol ulceration. The increase in nonacid gastric secretory volume by nicotine could partially explain its antiulcer effect. Furthermore, the acid secretory state of the stomach appears unrelated to the ulcerogenic property of ethanol.

Role of Gastric Mucosal Blood Flow in Cytoprotection

We compared the effects of graded doses of misoprostol (50-200 mg), omeprazole (12.5-50 mg), cimetidine (6.25-50 mg) and sucralfate (50-200 mg) on gastric mucosal blood flow as measured by laser Doppler flowmetry and gastric mucosal injury induced by ethanol. The results demonstrated that sucralfate, misoprostol and omeprazole, but not cimetidine, increased gastric mucosal blood flow in a dose-dependent manner and protected the mucosa against ethanol damage. The peak and summation blood flow were significantly greater with sucralfate than with misoprostol and omeprazole, but the degree of mucosal protection was similar. These results indicate that the increase in gastric mucosal blood flow, an action which is common to the three drugs, plays an important role in gastric mucosal protection, but other factors are also involved.

Endogenous prostaglandins: Its role in gastric mucosal blood flow and ethanol ulceration in rats

The involvement of endogenous prostaglandins (PGs) in modulating gastric mucosal blood flow (GMBF) is still unclear. The present study was designed to demonstrate the role of this autacoid in the basal GMBF and the restoration of blood flow after restriction of blood supply to the stomach. The ex-vivo gastric chamber was prepared and the GMBF was measured by a laser Doppler technique. 20% ethanol incubation for 10 min in the chamber increased the basal GMBF and lessened the reduction of blood flow induced by absolute ethanol. It also decreased lesion formation caused by ethanol. Indomethacin 5 mg/kg, given s.c 60 min before experimentation had the opposite effects. Ligation of the gastric artery for 20 min which reduced the GMBF by 60%, worsened ethanol ulceration. There was a marked rebound of the GMBF after the ligation was released. Indomethacin totally abolished the blood flow rebound and aggravated ethanol ulceration. However, 20% ethanol incubation significantly potentiated such a rebound in blood flow and reduced lesion formation. Indomethacin pretreatment reversed these actions, whereas misoprostol administration produced the similar effects as 20% ethanol. It is concluded that GMBF plays an important role in ethanol ulceration and both basal and rebound GMBF is probably modulated by endogenous PGs.