Stephen Patchett

Clot lysis by gastric juice: an in vitro study.

Gastric juice from patients with peptic ulcer disease and from patients with no upper gastrointestinal abnormality was studied in order to assess its effect on a formed fibrin clot. In both groups of patients gastric juice caused a marked increase in fibrinolysis as evidenced by a shortening of the euglobulin clot lysis time. This plasmin mediated fibrinolytic activity was found to be heat labile and only present in an acid environment. Addition of tranexamic acid or sucralfate to gastric juice almost completely reversed this effect, whereas pepstatin was only partially effective. It is probable that acid dependent proteases other than pepsin are responsible for the marked fibrinolysis. The ulcer healing agent sucralfate might be useful in those patients at risk of bleeding or rebleeding from active peptic ulcer disease.

The relation between gastric vitamin C concentrations, mucosal histology, and CagA seropositivity in the human stomach

Background—Vitamin C may be protective against gastric cancer though infection withHelicobacter pylori is associated with a reduction in intragastric concentrations of vitamin C. Aims—To examine the effects ofH pylori infection, gastric juice pH, the severity and extent of gastric inflammation, and CagA antibody status of the individual on gastric juice and mucosal vitamin C concentrations. Patients—One hundred and fifteen patients undergoing routine gastroscopy for investigation of dyspepsia. Methods—High performance liquid chromatography was used to determine vitamin C concentrations. CagA antibody was detected by western blot analysis. Results—Gastric juice ascorbic acid concentration was significantly lower in patients infected withH pylori compared with those uninfected (19.3 μmol/l (interquartile range (IQR) 10.7–44.5) versus 66.9 μmol/l (IQR 24.4–94.2), p=0.003). The reduction in gastric juice ascorbic acid concentration was inversely related to the severity of gastritis (p=0.01). CagA positive patients had significantly lower gastric juice ascorbic acid concentrations than CagA negative ones (14.8 μmol/l (IQR 7.9–52.2) versus 39 μmol/l (IQR 19.9–142.2), p=0.05). Decreased gastric juice dehydroascorbic acid concentrations were observed in patients with gastric atrophy and intestinal metaplasia. Mucosal ascorbic acid concentrations were also significantly lower in infected patients than uninfected patients (p=0.04). Conclusions—The reduction in gastric vitamin C concentrations is related to gastric juice pH, the severity and extent of gastritis, the presence of H pylori, and the CagA antibody status of the individual. These findings may have implications in H pyloriassociated carcinogenesis.

Identifying stage B colorectal cancer patients at high risk of tumor recurrence and death.

PURPOSE: This study was designed to determine clinical and pathologic variables associated with poor outcome following resection of Stage B colorectal cancer. METHODS: This was a retrospective study of 117 patients with Stage B cancer who underwent curative surgery and survived the postoperative period. Fourteen clinical and pathologic features were studied. Clinical data were extracted from a prospective colorectal cancer database, and histologic slides were retreived and examined by a pathologist blinded as to clinical details and outcome. RESULTS: After a median follow-up period of 8.2 years, bowel obstruction was significantly related to a poor prognosis (log-rank test; P=0.03). Extensive necrosis (P=0.01) and perineural invasion (P= 0.03) were also associated with decreased survival. Vascular invasion was associated with poor long-term outcome in the subgroup of patients with rectal (P=0.07) but not colonic (P=0.57) cancer. Multivariate regression analysis identified both tumor necrosis (P=0.01) and perineural invasion (P=0.03) as independently related to outcome. CONCLUSION: Further study of prognostic indicators might result in an algorithm to distinguish Stage B cases at high risk of tumor recurrence and death. Such patients could be included in future trials of adjuvant therapies.

Postprandial changes in portal haemodynamics in patients with cirrhosis.

Previous studies have shown that portal venous pressure increases in patients with cirrhosis after a protein meal. Since this increase may be mediated by an increase in hepatic blood flow or postsinusoidal hepatic vascular resistance, the present study was designed to examine the precise relation between the postprandial changes in these three variables in patients with cirrhosis and portal hypertension. Estimated hepatic blood flow (EHBF; indocyanine green clearance), portosystemic gradient (PSG; wedged free hepatic venous pressure), and postsinusoidal hepatic vascular resistance (PSR = PSG/EHBF) were measured simultaneously before and at 10 minute intervals after a high protein meal, containing 80 g protein, 40 g carbohydrate and 12 g fat (600 kcal) in nine patients (seven alcoholic, two non-alcoholic) with cirrhosis and portal hypertension. After the meal, the portosystemic gradient increased by 33% from mean (SEM) 15.6 (0.9) mm Hg to 20.7 (1.3) mm Hg, (p less than 0.01; Wilcoxon signed ranks test) within 30 minutes. Coincident with this increase in portosystemic gradient, estimated hepatic blood flow increased by 69.2% from 20.1 (1.7) ml/min/kg to 33.9 (2.5) ml/min/kg (p = 0.01), peak values occurring at 25 minutes, at which time the postsinusoidal hepatic vascular resistance had decreased by 31% from 1.10 (0.1) 10(-2) mm Hg/ml/min to 0.8 (0.5) 10(-2) mm Hg/ml/min (p = 0.01). These results suggest that the postprandial increase in portal venous pressure in patients with cirrhosis is mediated by an increase in hepatic blood flow and modified by a simultaneous decrease in postsinusoidal resistance.

Gastric α-tocopherol and β-carotene concentrations in association with Helicobacter pylori infection.

OBJECTIVE The effects of Helicobacter pylori infection and its associated gastric histology on alpha-tocopherol and beta-carotene concentrations in serum, gastric juice and antral mucosa were investigated in patients undergoing routine gastroscopy for investigation of dyspepsia. METHOD Eighty-six patients were studied. High-performance liquid chromatography was used to measure alpha-tocopherol and beta-carotene concentrations. H. pylori infection was assessed by histology, bacterial culture, rapid urease test and serology. RESULTS No obvious association was found between age, sex, smoking or endoscopic diagnosis and alpha-tocopherol or beta-carotene concentrations in serum, gastric juice and antral mucosa. However, alcohol drinkers had significantly lower antral mucosal and gastric juice beta-carotene concentrations compared to non-drinkers. Gastric juice beta-carotene concentration was markedly lower in patients infected with H. pylori than uninfected controls (2.9 nmol/l (interquartile range 0.3-4.3) versus 4.6 nmol/l (interquartile range 3.5-7.6), P = 0.01), but there was no significant difference in serum or gastric mucosal beta-carotene concentrations between the two patient groups. The presence of gastric atrophy and intestinal metaplasia was significantly associated with reduced mucosal alpha-tocopherol and beta-carotene concentrations. Furthermore, antral mucosal alpha-tocopherol concentrations decreased progressively as antral mucosal histology changed from normal to chronic gastritis alone and finally to atrophy and intestinal metaplasia. CONCLUSION Gastric alpha-tocopherol and beta-carotene concentrations are affected by H. pylori-associated gastric histological changes, and these findings suggest that H. pylori infection may not only impair the protective role of vitamin C, but also of alpha-tocopherol and beta-carotene in the stomach.

Changing patterns of sedation use for routine out‐patient diagnostic gastroscopy between 1989 and 1998

Knowledge of sedation trends for upper gastrointestinal endoscopy is important for health service planning, particularly in view of rapidly increasing demands on endoscopy services. However, no data are available on sedation trends in Britain over the past 10 years.

Ornithine decarboxylase activity is a marker of premalignancy in longstanding Helicobacter pylori infection.

BACKGROUND: Longstanding Helicobacter pylori infection may increase the risk of developing gastric adenocarcinoma. The sequence of chronic active gastritis leading to gastritis with atrophy and subsequent intestinal metaplasia is thought to be a key step in gastric carcinogenesis. Ornithine decarboxylase (ODC) activity is increased in some pre-malignant gastrointestinal conditions and is essential for malignant transformation in vitro. AIMS: To measure ODC activity in the antrum of H pylori infected and non-infected subjects and to relate this to histological abnormalities associated with recent and longstanding H pylori infection. METHODS: Six antral mucosal biopsy specimens were obtained from 75 patients for detailed histological assessment and measurement of ODC activity. Samples were measured in duplicate and results expressed as median, interquartile range in pmol/mg protein/h. RESULTS: ODC activity was significantly higher in H pylori positive (164, 88-259 pmol/mg/h) than H pylori negative subjects (99.8, 55-158 pmol/mg/h, p = 0.003). However the presence of gastritis, irrespective of the severity of inflammation or activity had no influence on ODC activity. Gastritis with atrophy was associated with increased ODC activity, which was closely related to the severity of the atrophy (p = 0.01). Similarly, ODC activity was significantly increased in subjects with intestinal metaplasia (196, 83-25) compared with those without intestinal metaplasia (111.7, 65-175, p < 0.04). CONCLUSIONS: These results indicate that the histological changes associated with longstanding H pylori infection rather than inflammation alone are associated with increased polyamine biosynthetic activity. This may be relevant to H pylori associated gastric carcinogenesis.

A double‐blind randomized trial of low‐dose versus high‐dose topical anaesthesia in unsedated upper gastrointestinal endoscopy

Background: Upper gastrointestinal endoscopy is frequently performed on unsedated subjects. Pharyngeal anaesthesia is thought to improve patient tolerance to the procedure but the optimum dose of anaesthesia is not known. The aim of this study was to assess the benefits of low‐dose vs. high‐dose topical anaesthesia in unsedated gastroscopy.

Nonsteroidal anti-inflammatory drug-induced diaphragms and ulceration in the colon.

The toxic effects of nonsteroidal anti-inflammatory drugs (NSAIDs) on the small bowel have been reported extensively. A growing number of reports of toxic effects of NSAIDs on the colon have appeared recently. The clinical presentation, endoscopic appearances and histological findings of so-called NSAID colopathy are quite varied, as illustrated by a series of four patients described in this report. Presenting symptoms and signs in this series include iron-deficiency anaemia and crampy abdominal pain, but alteration of bowel habit, weight loss, and even nausea and vomiting have also been described. One patient in this series has large-bowel diaphragms, considered by some to be pathognomonic of NSAID effects. Each of the four patients had right-sided colonic lesions only, possibly supporting a direct toxic effect of NSAIDs. Management usually involves simply stopping the offending NSAID. A review of the literature on this under-recognized entity is presented.

Effective palliation of a colovaginal fistula using a self-expanding metal stent

Pal l i a t ion of g a s t r o i n t e s t i n a l m a l i g n a n c y , par t ic u l a r ly c a r c i n o m a of t he e sophagus , h a s b e e n g r ea t l y fac i l i t a ted in r ecen t y e a r s by the in t roduc t ion of endoscopic s ten t ing . In the e sophagus , endoscopic p l a c e m e n t of a p las t ic or se l f -expand ing m e t a l s t en t can r e s to re a func t iona l d i a m e t e r to al low oral i n t a k e of food a n d reduce regurg i t a t ion . Me ta l s t en t s h a v e been ga in ing in p o p u l a r i t y becaus e of t he i r ease of i n se r t i on a n d ve ry low compl ica t ion ra tes . 1 Endoscopic pa l l i a t ion of s t r i c t u r i ng la rge bowel tumor s h a s un t i l r ecen t ly b e e n r e s t r i c t ed to l a se r t he r apy . I so l a t ed r epo r t s do h o w e v e r sugges t t h a t m e t a l s t en t i n se r t i on into the r e c t u m is a v iab le a l t e r n a t i v e for pa l l i a t ion of obs t ruc t ing rec ta l cancer.2, 3 In th is repor t , we descr ibe the use of a se l f expand ing m e t a l s t e n t for s y m p t o m a t i c t r ea t m e n t of a r ec tovag ina l f i s tu la in a p a t i e n t who would o the rwise h a v e r equ i r ed a colos tomy for s y m p t o m relief.