Biomedical subjects
J S Kirkham
Publications and source records attributed to J S Kirkham.
Oesophageal cancer in gastric surgery patients.
Oesophageal adenocarcinoma (which has been steadily increasing in incidence during the last 20 years) is thought to be promoted by gastric reflux. In a cohort of 5018 gastric surgery patients, 19 of whom developed oesophageal cancer, there was no increased proportion of adenocarcinomas. We conclude that the hypothesized aetiology was not supported.
Faecal bile acids and bowel cancer risk in gastric-surgery patients.
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Relation between severity and extent of precancerous lesions in the postoperative stomach.
The relation between the severity and extent of precancerous lesions in a precancerous condition of the stomach was assessed, to find a means of reducing the endoscopic workload required for the detection of such lesions. 87 subjects who had had gastric surgery for peptic ulcer more than 20 years ago underwent gastric endoscopy and biopsy. Severity of dysplasia correlated with its extent. Severity of intestinal metaplasia correlated with its extent and with severity of dysplasia. Type of operation, but not sex or type of ulcer, was the factor most strongly associated with dysplasia. Previous Billroth II operations were more strongly associated with occurrence of dysplasia (85%) than were other operations. In patients with previous Billroth II operations, moderate and severe dysplasia were commoner around the stoma (37%) than in the body (10%). These findings indicate that there is a relation between the severity and extent of precancerous lesions, which suggests that patients with dysplasia have widespread gastric mucosal instability. They also indicate that, if endoscopic screening is limited to Bilroth II subjects and if biopsies are limited to the stoma, endoscopic workload can be reduced by 85%, with only a small reduction (15%) in detection of moderate and severe dysplasia.
Randomized comparison of Nd YAG laser, heater probe, and no endoscopic therapy for bleeding peptic ulcers.
Of 550 patients admitted with acute upper gastrointestinal hemorrhage, 143 with peptic ulcers containing stigmata of recent hemorrhage accessible to endoscopic therapy were included in a randomized comparison of neodymium yttrium aluminum garnet laser, heater probe, and no endoscopic therapy. The rebleeding rate in laser-treated patients (20%) was significantly less than in controls (42%; p less than 0.05), but in heater probe-treated patients (28%) it was not significantly different from either of the other two groups. The mortality rate in the laser group (2%) was not significantly different from either the heater probe (10%) or the control (9%) group. This trial has confirmed the efficacy of the Nd YAG laser but not that of the heater probe in the prevention of rebleeding from recently bleeding peptic ulcers.
Thermodynamic effects of bile acids in the stomach.
The surface thermodynamic effects of bile acids in the stomach were assessed in 48 subjects who had undergone gastric surgery for peptic ulcer disease and in 52 controls with medically healed ulcers. We derived values for surface tension of gastric mucosa from contact angle using a goniometer and measured the surface tension of gastric juice by the drop-weight method. Subjects with gastric surgery had higher median fasting bile acid concentrations than controls (1.2 vs. 0.1 mmol/L; P less than 0.0001), higher mean mucosal surface tension (51.9 vs. 47.9 mN/m; P less than 0.0001), and lower mean surface tension of gastric juice (43.2 vs. 51.7 mN/m; P less than 0.0001). Subjects who had had a Billroth II gastrectomy (n = 19) had higher bile acid concentrations (5.8 vs. 0.6 mmol/L; P less than 0.01), higher mucosal surface tension (53.7 vs. 50.3 mN/m; P less than 0.05), and lower gastric juice surface tension (41.3 vs. 47.1 mN/m; P less than 0.05) than those who had a vagotomy and drainage procedure (n = 17). Overall, intragastric bile acid concentration correlated directly with surface tension of gastric mucosa (r = 0.51, P less than 0.0001) and inversely with that of gastric juice (r = -0.60, P less than 0.0001). In conclusion, the interfacial energy barrier at the surface of the gastric mucosa is overcome in the presence of intragastric bile acids.
Occupational and socioeconomic factors associated with peptic ulcer and with cancers following consequent gastric surgery.
Over 3000 patients, treated surgically for peptic ulcers, were assigned to a Social Class and Occupation Group using information obtained either from their death certificates or from their hospital notes. An analysis of the relationship of socioeconomic status and occupation with the site of original ulcer and the risk of cancer is reported. The major observations were: (a) an association of gastric ulcer with manual and of duodenal ulcer with non-manual Social Class; (b) an association of gastric cancer with dusty occupation and colorectal cancer with professional and managerial workers; and (c) no association between post-surgery gastric cancer risk and social class. This implies that the early stages of gastric carcinogenesis are related to poor socioeconomic conditions but the progression from the precursor lesion (in this case gastric ulcer) to gastric cancer is not, and is consistent with the multistage hypothesis of gastric carcinogenesis proposed by Correa [Diet and Human Carcinogenesis (Edited by Joosens, J. V., Hill, M. J. and Geboers, J.), pp. 109-115. Excerpta Medica, Amsterdam (1985)].
Ivalon (polyvinyl alcohol) sponge presenting as an extrarectal mass.
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Mortality from colorectal and breast cancer in gastric-surgery patients.
In a preliminary "years at risk" analysis of 5018 patients treated surgically for peptic ulcer at St. James Hospital, Balham, between 1940 and 1960, there was an increase in mortality from colorectal cancer 20 or more years after operation (1.6 fold; p less than 0.05) and an increase in mortality from breast cancer (4.0 fold; p less than 0.001). During the first 20 post-operative years there was an apparent decrease in mortality from both cancers (relative rate = 0.7 (NS) for colorectal and 0.5 (p less than 0.01), for breast cancer). The excess risk of colorectal cancer after a 20 year latency was almost entirely due to the 9.5 fold (p less than 0.001) excess risk in the 381 female gastric ulcer patients treated by Billroth I operation, and the 8.0 fold (p less than 0.05) excess mortality for the small group of 123 female patients who had vagotomy for duodenal ulcer. The apparent decreased risk during the first 20 post-operative years was entirely due to the 5-fold decrease (p less than 0.01) in risk in the 659 male patients treated by Billroth I surgery for gastric ulcer. The ratio of colon: rectal cancers was very much higher in gastric ulcer than in duodenal ulcer patients (5.6 compared to 1.8) and higher in females than in males (6.0 compared to 2.4). The excess risk of breast cancer after a 20 year latency was 4-fold in both gastric ulcer and duodenal ulcer patients.(ABSTRACT TRUNCATED AT 250 WORDS)
Urinary N-nitrosoproline excretion: a further evaluation of the nitrosamine hypothesis of gastric carcinogenesis in precancerous conditions.
Measurement of N-nitroso compounds in gastric juice by different methods has given conflicting results. In order to resolve this controversy, we have assessed endogenous nitrosation by the independent N-nitrosoproline excretion test in subjects who had previously undergone gastric juice analysis by one of these methods. Ten Polya gastrectomy, 10 pernicious anaemia and nine matched control subjects were fed 380 mg of nitrate in beetroot juice and 500 mg proline. N-nitrosoproline (N-Pro) synthesised intragastrically from these precursors, and quantitatively excreted by the kidneys, was measured in 24 hour urine samples (collection checked by creatinine clearance). N-Pro excretion (mean +/- SEM) was reduced (p less than 0.01) in pernicious anaemia (1.1 +/- 0.8 ng/day) compared with matched control (18.0 +/- 7.2 ng/day), and also tended to be lower (NS) in polya gastrectomy (3.2 +/- 2.3 ng/day). Twenty four hour intragastric pH was monitored on a separate occasion in 23 of the 29 subjects; 13 were hypoacidic (pH greater than 4 greater than 50% of 24 hours) and 10 were acidic. N-Pro yields were reduced (p less than 0.01) in the hypoacidic group (0.9 +/- 0.6 ng/day) compared with the acidic group (17.9 +/- 6.6 ng/day), and N-Pro was negatively associated with mean intragastric pH (tau = -0.53, p = 0.001). We conclude that endogenous synthesis of this specific N-nitroso compound is favoured by low rather than high pH. These results are concordant with those previously reported in gastric juice from the same subjects and suggest that nitrosation is chemically rather than bacterially mediated, contrary to the nitrosamine hypothesis of gastric carcinogenesis.
Increased risk of cancer at multiple sites after gastric surgery for peptic ulcer.
Of 5018 patients who had undergone gastric surgery at St James Hospital, Balham, at least 25 years ago, death certificates have been received for 2768, whilst 1746 patients are still alive and are flagged (Office of Populations, Censuses and Surveys (OPCS) will notify us of their death and its cause) and only 504 could not be traced. Mortality from cancers of various organs has been determined using a 'years at risk' calculation in five year bands. There was no increase in mortality risk from any cancers during the first 15 postoperative years, but from 20 years after operation there was a significant excess risk not only of cancer of the stomach (4.5-fold), but also of the large bowel (1.6-fold), bronchus (3.9-fold), pancreas (4.0-fold), biliary tract (9.1-fold), oesophagus (2.3-fold), bladder (2.4-fold), breast (4.0-fold), and cancer of all sites (3.3-fold). These findings are consistent with the production in the operated-upon stomach of circulating carcinogens with a 20 year latency period.
Gastric hypoacidity as a risk factor for gastric and other cancers.
Evidence is presented and discussed to test the hypothesis that the excess risk of gastric cancer observed in patients with decreased gastric acidity is caused by metabolites of nitrite, possibly N-nitroso compounds.
Evaluation of the nitrosamine hypothesis of gastric carcinogenesis in man.
Patients who had undergone a Billroth II gastrectomy (PG) or had pernicious anaemia (PA) and healthy matched control subjects (MC) participated in 24-h studies in which bacteria, nitrite and N-nitroso compounds (NOC) were measured in gastric juice and N-nitrosoproline (NPRO) in urine. Consistent with the nitrosamine hypothesis, intragastric levels of bacteria and nitrite were positively related to intragastric pH, but, contrary to the hypothesis, NOC in gastric juice and NPRO in urine were negatively related to intragastric pH.
Controlled trial of Nd-YAG laser photocoagulation in bleeding peptic ulcers.
The efficacy of Nd-YAG laser photocoagulation in the endoscopic control of haemorrhage from peptic ulcers was shown in a controlled trial. 527 patients admitted consecutively with acute upper gastrointestinal haemorrhage underwent urgent endoscopy. Peptic ulcers were seen in 260. All 138 ulcer patients with stigmata of recent haemorrhage (SRH) accessible to laser therapy were included in the trial (26 inaccessible, 96 no SRH). Patients were stratified into three groups--those with a visible vessel, those with other SRH, and those with clot that could not be washed off before therapy. Laser and control groups were well matched for other factors known to influence prognosis. Overall, 7/70 laser-treated and 27/68 control ulcers rebled (p less than 0.001). Rebleeding occurred from 6/39 treated and 23/43 control ulcers with a visible vessel (p less than 0.001); 0/17 treated and 1/13 ulcers with other SRH (NS); and 1/13 treated and 2/11 control ulcers with overlying clots (NS). 7/70 treated but 24/68 controls required emergency surgery (p less than 0.005). 1 treated patient but 8 control patients died after an episode of rebleeding (p less than 0.05).
Mortality from gastric cancer following gastric surgery for peptic ulcer.
When compared with a matched population group, 4466 ulcer patients who had had gastric surgery between 1940 and 1960 showed no difference in the risk of death from gastric cancer in the first 20 years of follow-up but a 4.5-fold increase thereafter. In duodenal ulcer patients there was an initial decrease in risk followed by a 3.7-fold increase after 20 or more years. Since the initial decrease was seen only in the gastrectomy patients and not in those who had truncal vagotomy and drainage, it may have been due to the reduction in mucosal surface. The increased risk 20 years after duodenal ulcer surgery was greater in vagotomy patients than in gastrectomy patients. In gastric ulcer patients a 3.0-fold increase in risk for the first 20 years rose to a 5.5-fold increase thereafter. After 20 years, patients treated with the Bilroth II operation were at higher risk than those treated with Bilroth I, consistent with a role for bile reflux in gastric carcinogenesis. The finding that the risk differs according to original pathology and type of operation may explain the discrepancies between previous studies.
Nature of the bleeding vessel in recurrently bleeding gastric ulcers.
An unselected consecutive series of 826 patients admitted for acute upper gastrointestinal bleeding underwent urgent endoscopy. Peptic ulcers were found in 402 (49%). Of the 329 ulcer craters that could be fully examined, visible vessels were identified in 156 (47%), other stigmata of recent hemorrhage in 66, and no stigmata of recent hemorrhage in 107. One hundred twenty-nine patients with stigmata of recent hemorrhage (93 of whom had visible vessels) randomly allocated to no endoscopic treatment were observed for evidence of further bleeding. Fifty-four of the 93 patients (58%) with visible vessels rebled, compared with 2 of 36 (6%) with other stigmata of recent hemorrhage. No patient without stigmata of recent hemorrhage rebled. Twenty-seven patients in whom a visible vessel in a gastric ulcer was identified at endoscopy underwent urgent partial gastrectomy because of recurrent bleeding. The vessel identified at endoscopy was found in 26 of 27 resection specimens (96%). The arterial vessel wall protruded above the surface of the ulcer crater in 10 specimens, and clot in continuity with a breach in the vessel wall protruded in a further 10 specimens. Postoperative angiography, when technically possible, showed that the breached artery ran across the base of the ulcer in all of these specimens. Pathological changes were common in the bleeding artery and included arteritis in 24 of 29 (83%) eroded arteries found in these specimens, with aneurysmal dilatation in 14 of 27 (52%) bleeding points that could be fully examined. The ulcer had penetrated to serosa in 13 specimens (45%). The bleeding artery had a mean external diameter of 0.7 mm with a range of 0.1-1.8 mm. This study provides new information about the nature of the bleeding vessel in gastric ulcers, and some of this information is relevant in planning studies of endoscopic therapy for bleeding peptic ulcers. It validates the endoscopic identification of a visible vessel, and confirms that such identification has a high predictive value for the development of recurrent hemorrhage.
Evaluation of the nitrosamine hypothesis of gastric carcinogenesis in precancerous conditions.
A 24 hour gastric aspiration study was carried out on nine Polya gastrectomy, eight pernicious anaemia, and nine matched control subjects. Intragastric pH, bacteria, nitrite, and N-nitroso compounds were assessed half hourly whilst ambulant and hourly when in bed. Both total and nitrate reducing bacterial counts were positively related to pH (chi 2 = 279.3; p less than 0.001), as was nitrite concentration (F = 19.1; p less than 0.0001). By contrast, total (F = 40.6; p less than 0.0001) and stable (F = 257.4; p less than 0.0001) N-nitroso compound concentrations were negatively related to pH. Clear differences in these gastric juice factors were not apparent between matched control and either pernicious anaemia, or Polya gastrectomy because the Polya gastrectomy and matched control groups were heterogeneous for gastric acidity. Thus, although eight of eight pernicious anaemia subjects were hypoacidic (defined as intragastric pH greater than 4 for greater than 50% of both daytime and night time periods), only five of nine Polya gastrectomy and two of nine matched control subjects were hypoacidic. When subjects were rearranged into hypoacidic (n = 15) and acidic (n = 11) groups, bacterial counts (p less than 0.01) and nitrite concentrations (p less than 0.01) were higher, whereas N-nitroso compounds tended to be lower (NS) in the hypoacidic group. These data suggest that, although hypoacidity predisposes to bacterial overgrowth and nitrite generation, it does not enhance nitrosation. Instead, this is maximal at low pH, suggesting chemical rather than bacterial nitrosation, contrary to the nitrosamine hypothesis of gastric carcinogenesis.
Talking to patients about cancer.
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