Background and aims: Oesophageal adenocarcinoma frequently develops on a background of metaplastic Barrett's epithelium. The development of malignancy is accompanied by genetic alterations, which may be promising biomarkers of disease progression. Methods: A case control study was conducted nested within a large unselected population based cohort of Barrett's patients. Incident oesophageal malignancies and high grade dysplasias were identified. For each case up to five controls were matched on age, sex, and year of diagnosis. Biopsies from the time of diagnosis of Barrett's epithelium were stained immunohistochemically for TP53, cyclin D1, cyclooxygenase 2 (COX-2), and b-catenin proteins. Results: Twenty nine incident oesophageal malignancies and six cases of high grade dysplasia were identified. The odds of diffuse or intense TP53 staining were substantially elevated in biopsies from patients who developed oesophageal adenocarcinoma compared with controls (odds ratio (OR) 11.7 (95% confidence interval (CI) 1.93, 71.4)). This difference was also present when all cases were considered (OR 8.42 (95% CI 2.37, 30.0). Despite the association with TP53 staining, only 32.4% of cases had an initial biopsy showing diffuse/intense TP53 staining. There were no significant associations between cyclin D1, COX-2, or b-catenin staining and case control status. The OR for positive staining for both TP53 and COX-2 was markedly increased in cases compared with controls (OR 27.3 (95% CI 2.89, 257.0)) although only 15% of cases had positive staining for both markers. Conclusions: Immunohistochemical detection of TP53 expression is a biomarker of malignant progression in Barrett's oesophagus but sensitivity is too low to act as a criterion to inform endoscopic surveillance strategies. Additional biomarkers are required which when combined with TP53 will identify, with adequate sensitivity and specificity, Barrett's patients who are at risk of developing cancer.

Although a high prevalence of antibodies to Helicobacter pylori has been documented within families, culture and DNA typing of strains from infected children and their parents has not been evaluated. This study aimed to analyse H pylori infection within family groups. Endoscopy, gastric biopsy, and H pylori culture were performed on all eight parents of four children who presented with dyspepsia and who had a positive H pylori culture. All biopsy specimens were cultured on Columbia based blood agar under microaerophilic conditions for four days. The DNA from each strain was extracted and electrophoretic patterns were compared after digestion with restriction endonucleases Hae III or Hind III. Ribotyping using a biotinylated cDNA probe prepared from 16S and 23S rRNA of H pylon NCTC 11638 was also used. Seven of the parents were positive for H pylorn on urease testing, histology, and on culture. DNA typing showed the same or a similar strain to be present in at least two family members in three of the four family groups. In family 1, the mother, father, and child all had an identical strain; in family 2, father and son had a similar related strain; father and mother had the same strain in family 3; and all strains were unique in family 4. These data provide evidence for either intrafamilial cross infection or a common source of infection within family groups. (Gut 1993; 34: 1348-1350 Helicobacter pylon is recognised as a significant cause of chronic antral gastritis and important in the aetiology of peptic ulceration.' There is also evidence to support a role as a risk factor for gastric carcinoma.2 5 It is known that the prevalence increases with age6 and that while the incidence in children is lower than that in adults, intrafamilial clustering has been shown. DNA TYPING H pyloni isolates from four children and their parents, plus two isolates chosen randomly from unrelated individuals were incubated on brain heart infusion agar supplemented with 5% v/v horse blood and 1% v/v isovitalex (Oxoid) for 48 hours at 37%, under microaerophilic conditions (5% 02, 5% C02, 2% H2, 88% N2). Chromosomal DNA was isolated and purified from each isolate using the guanidium thiocyanate reagent method.'0 The purified DNA was incubated with the restriction endonuclease (Hae III) for four hours at 37°C and the digests were electrophoresed at 30 v for 16 hours in a horizontal agarose gel. After electrophoresis the gels were stained with ethidium bromide and photographed. Strain DNAs which did not cut with Hae III were subjected to Hind III digestion. For ribotyping, the gels were then transferred to nylon membranes by means of vacublotting. A biotinylated cDNA probe was prepared from 16S and 23S rRNA of H pylori NCTC 11638 using reverse transcriptase. Biotinylation was achieved by the incorporation of biotin-16-dUPT. The membranes were then hybridized by standard procedures for 16 hours at 42°C, using the biotinylated cDNA probe. Restriction digest patterns and ribopatterns were compared. Details of DNA typing methods have b...

hospital intubation without drugs was hopeless, 3 but we found that 8% of patients survived. The number was small, with the lower limit of the confidence interval of 0.2% just equal to the mean survival reported by the helicopter service.Anaesthesia and intubation can be complicated by head and facial injuries, cervical fractures, risk of oesophageal intubation, aspiration, circulatory deterioration, and increased intracerebral pressure. The environment out of hospital is different from in hospital and support and resources are limited. We question whether anaesthesia and intubation of trauma patients can be mastered and routine be maintained by ambulance personnel.

Summary This study examined the association between 1 7p allelic loss, p53 gene mutation, p53 protein expression and DNA aneuploidy in a series of adenocarcinomas arising in the oesophagus and gastric cardia. 1 7p allelic loss was detected in 79% (15 of 19) of oesophageal and in 83% (29 of 35) of gastric adenocarcinomas. p53 mutations were detected in 70% (14 of 20) and 63% (26 of 41) of oesophageal and of gastric adenocarcinomas respectively. Both tumour types were associated with a predominance of base transitions at CpG dinucleotides. In five cases of oesophageal adenocarcinoma, the same mutation was detected both in tumour and in adjacent dysplastic Barrett's epithelium. Diffuse p53 protein expression was detected in 65% (13 of 20) and 59% (24 of 41) of oesophageal and of gastric tumours, respectively, and was associated with the presence of p53 missense mutation (Chi-squared, P < 0.0001). DNA aneuploidy was detected in 80% (16 of 20) of oesophageal and in 70% (28 of 40) of gastric tumours. No association was found between p53 or DNA content abnormalities and tumour stage or histological subtype. In conclusion, this study detected a similar pattern of p53 alterations in adenocarcinoma of the oesophagus and gastric cardia -molecular data consistent with the observation that these tumours demonstrate similar clinical and epidemiological features.

(Accepted 11 March 1999)Influence of hospital and clinician workload on survival from colorectal cancer: cohort study AbstractObjective To determine whether clinician or hospital caseload affects mortality from colorectal cancer. Design Cohort study of cases ascertained between 1990 and 1994 by a region-wide colorectal cancer register.Outcome measures Mortality within a median follow up period of 54 months after diagnosis. Results Of the 3217 new patients registered over the period, 1512 (48%) died before 31 December 1996. Strong predictors of survival both in a logistic regression (fixed follow up) and in a Cox's proportional hazards model (variable follow up) were Duke's stage, the degree of tumour differentiation, whether the liver was deemed clear of cancer by the surgeon at operation, and the type of intervention (elective or emergency and curative or palliative intent). In a multilevel model, surgeon's caseload had no significant effect on mortality at 2 years. Hospital workload, however, had a significant impact on survival. The odds ratio for death within 2 years for cases managed in a hospital with a caseload of between 33 and 46 cases per year, 47 and 54 cases per year, and >55 cases per year (compared to one with ≤ 23 cases per year) were respectively 1.48 (95% confidence interval 1.03 to 2.13), 1.52 (1.08 to 2.13), and 1.18 (0.83 to 1.68).Conclusions There was no detectable caseload effect for surgeons managing colorectal cancer, but survival of patients treated in hospitals with caseloads above 33 cases per year was slightly worse than for those treated in hospitals with fewer caseloads. Imprecise measurement of clinician specific "events rates" and the lack of routinely collected case mix data present major challenges for clinical audit and governance in the years ahead.

Aims-To investigate the immunohistochemical staining of normal, hyperplastic, and neoplastic adrenal cortex with a monoclonal antibody against inhibin. Also, to determine whether immunostaining with this antibody is useful in diVerentiating between adrenal cortical neoplasms and other tumours involving the adrenal gland that might mimic them. Methods-Normal adrenal tissue (n = 20) and specimens from cases of adrenal hyperplasia (n = 13), adrenal cortical adenoma (n = 15), adrenal cortical carcinoma (n = 4), phaeochromocytoma (n = 8), and adrenal metastatic tumour (n = 7) were stained with a monoclonal antibody against the subunit of human inhibin. Results-Positive staining with the antiinhibin monoclonal antibody was seen in all normal adrenal glands. Immunoreactivity was largely confined to the inner cell layers of the adrenal cortex, with no staining of the adrenal medulla. All hyperplastic adrenal glands and adrenal cortical adenomas and carcinomas were also immunoreactive. The other tumours studied were negative. Conclusions-There is consistent immunoreactivity with the anti-inhibin monoclonal antibody in normal adrenal cortex and in hyperplastic and neoplastic adrenal cortical lesions. In the normal adrenal cortex, positive staining is mainly confined to the zona reticularis. Other neoplasms involving the adrenal gland are negative. Immunohistochemical staining with anti-inhibin monoclonal antibody, performed as part of a panel, may prove to be of value in the distinction between adrenal cortical carcinoma and phaeochromocytoma or metastatic tumour. (J Clin Pathol 1998;51:114-116)

We report 40 cases in one family of an autosomal dominant bone dysplasia, which, though similar in some aspects to Paget's disease, seems unique in some features and in its natural history. The disease shows both general and focal skeletal changes, the latter being mainly in the limbs with an onset from the second decade. Progressive osteoclastic resorption is accompanied by medullary expansion which leads to pain, severe deformity and a tendency to pathological fracture. The serum alkaline phosphatase and urinary hydroxyproline are variably elevated, while other biochemical indices are normal. Most patients had an associated deafness of early onset and loss of dentition. No previous description of this disease has been found in the literature.

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