Staging of oesophageal adenocarcinoma.
Explore the source record for details and available documents.
Adenocarcinoma↗
Biomedical subjects
R H Hardwick
Publications and source records attributed to R H Hardwick.
Association between Streptococcus milleri and abscess formation after appendicitis.
Abscesses after appendicitis occur in some patients despite timely surgery and antibiotics. The Streptococcus milleri group of bacteria are commonly associated with gastrointestinal abscesses. This study investigated the relationship between S. milleri and abscess formation after appendicectomy a total of 301 patients (172 males, 129 females, median age 22 years) with appendicitis were identified retrospectively from the hospital PAS computer system who had an appendicectomy and peritoneal bacteriology swabs taken. All but one patient had prophylactic antibiotics. Patients were divided into three groups according to peritoneal bacteriology: group 1 (S. milleri +/- mixed faecal organisms, n = 61); group 2 (mixed faecal organisms, n = 126); and group 3 (sterile, n = 114). The chi squared and Student t-tests were used for statistical analysis. Thirteen (21%) of group 1 patients developed an intra-abdominal abscess compared with 4 (3%) in group 2 and 2 (1.7%) in group 3 (P < 0.0001). There was no difference in the prevalence of gangrenous or perforated appendicitis between groups 1 and 2 (56% versus 52%) but these worse forms of appendicitis were less common in group 3 (22%). Group 1 patients had a mean total hospital stay of 10 days versus 6 days for group 2 and 4 days for group 3 (P < 0.001). S. milleri was associated with a 7-fold increase in abscess formation after appendicectomy and a longer hospital stay. Antibiotic prophylaxis did not prevent this complication.
Abdominal Abscess↗
Amplification of cyclin D1 and MDM-2 in oesophageal carcinoma.
AIMS: This study investigated amplification of the cyclin D1 and MDM-2 genes, and overexpression of the cyclin D1 gene product, in oesophageal carcinoma. METHODS: Paired tumour and normal DNA samples from 26 oesophageal adenocarcinomas and 19 squamous cell carcinomas were analysed by Southern blotting with specific DNA probes for cyclin D1 and MDM-2, and for a control gene (alpha-lactalbumin). The cyclin D1 and MDM-2 gene copy numbers were calculated for each tumour. Expression of the cyclin D1 gene was assessed by immunohistochemical analysis of its protein product. RESULTS: Cyclin D1 gene amplification (by a factor of between two and six) was identified in seven tumours (16%). MDM-2 gene amplification (by a factor of between two and 11) was identified in 10 tumours (22%). Overexpression of cyclin D1 protein was identified in eight tumours and was significantly associated with gene amplification (P=0.04; Fisher's exact test), and with early T stage (P=0.01; Fisher's exact test). CONCLUSIONS: Cyclin D1 and MDM-2 amplification and cyclin D1 overexpression occur, although infrequently, in the development of oesophageal carcinoma. Cyclin D1 overexpression may influence tumour behaviour, causing the disease to present at an earlier T stage. The mechanism for this effect is unclear, and warrants further investigation.
Adenocarcinoma↗
Laparoscopic splenectomy in pregnancy.
A laparoscopic splenectomy during pregnancy is described in this case report. The operation took place at 18 weeks' gestation for life-threatening thrombocytopaenia secondary to antiphospholipid syndrome that had failed to respond to medical therapy. The patient made a full and rapid recovery and was delivered of a healthy baby girl at term.
Adult↗
Loss of heterozygosity at microsatellite marker sites for tumour suppressor genes in oesophageal adenocarcinoma.
AIMS: Loss of cell cycle control is an important step in the development of human tumours. A number of tumour suppressor genes are involved in cell cycle control, including p16, p53 and Rb. The aim of this study was to seek evidence of deletions of these genes in oesophageal adenocarcinoma. METHODS: Paired (tumour and normal squamous epithelium) frozen tissue samples from 12 patients were analysed by polymerase chain reaction (PCR) for loss of heterozygosity (LoH) at five microsatellite marker sites (two each for p16 and Rb, one for p53). Aneuploid tumour cell populations were sorted by flow cytometry prior to PCR, to eliminate stromal cell contamination. RESULTS: Of the 12 tumours, 11 (92%) had LoH at one or more loci. LoH at the p53 locus occurred in nine of 12 tumours, at one or both p16 loci in seven of 11 tumours, and at one or both Rb loci in eight of 12 tumours. Five tumours had LoH at two tumour suppressor gene loci, and a further four tumours had LoH at loci for all three genes. CONCLUSIONS: Allelic deletions of p53, p16 and Rb are common in oesophageal adenocarcinoma, and may be important in the development of this disease.
Adenocarcinoma↗
Investigation of oesophageal adenocarcinoma for viral genomic sequences.
Overexpression of the tumour suppressor gene product p53 is common in oesophageal adenocarcinoma. This may be due to gene mutation, but overexpression can also result from complexing between viral proteins and p53; a number of viruses are causally linked with malignancy. This study therefore investigated the prevalence in oesophageal adenocarcinoma of viruses whose gene products are capable of interacting with p53. Seventeen tumours and 17 normal oesophagi were screened for specific DNA sequences from human papilloma virus (HPV), Adenovirus type 12, Epstein-Barr Virus (EBV), and cytomegalovirus (CMV). Frozen sections were analysed by polymerase chain reaction, and results were confirmed by Southern blot hybridization. Overexpression of p53 was studied immunohistochemically. Overexpression of p53 was identified in 11 of 17 tumours. No viral sequences were detected for HPV, CMV, or Adenovirus in any tumour. EBV sequences were found in eight of 17 tumours, and eight of 17 negative controls. There is therefore no evidence of HPV 16, 18 and 33, Adenovirus 12 or CMV infection in oesophageal adenocarcinoma. EBV infection in the oesophagus is of doubtful significance, in view of the high incidence in the control population. Overexpression of p53 cannot be explained by complexing with common viral proteins, and must be related to other intracellular mechanisms.
Adenocarcinoma↗
Immunohistochemical detection of p53 and c-erbB-2 in oesophageal carcinoma; no correlation with prognosis.
TNM staging of oesophageal cancer provides significant prognostic information but its clinical impact is limited as many patients present with advanced disease (i.e. T3N1). Additional prognostic markers may help separate those with 'good' and 'bad' prognosis tumours and so help with decisions such as selection for adjuvant therapy. p53 and c-erbB-2 overexpression may correlate with poor prognosis in oesophageal cancer, but this is uncertain. This study aimed to investigate the value of these biomarkers as prognostic indicators in resected oesophageal cancer. Two hundred and five oesophageal tumours (127 adenocarcinoma, 78 squamous) resected by a single surgeon between June 1979 and January 1991 were investigated for p53 and c-erbB-2 overexpression using DO-7 and CB-11 immunohistochemistry. Patient survival was analysed by Kaplan-Meir life tables. Median survival was 61 weeks (range: 5-747) and survival diminished significantly with increasing UICC stage (P < 0.0001). Sixty-eight per cent of squamous tumours and 66% of adenocarcinomas overexpressed p53 but there was no statistically significant correlation with prognosis. Twenty-six per cent of squamous tumours and 23% of adenocarcinomas overexpressed c-erbB-2, but again this did not correlate with survival. p53 and c-erbB-2 are commonly overexpressed in oesophageal cancer but do not appear to be related to prognosis in this large series of resected oesophageal cancers and other candidate biomarkers must be sought.
Adenocarcinoma↗
Human papillomavirus and oesophageal squamous cell carcinoma in the UK.
Human papillomavirus (HPV) has previously been identified in up to 67% of squamous cell carcinomas of the oesophagus. In particular, HPV types of 16 and 18 are believed to play an important role in neoplastic transformation, by means of their oncoproteins E6 and E7. Most of these studies, however, pertain to areas of high incidence of squamous cell carcinoma of the oesophagus (the Far East and South Africa). It is not known if HPV plays any role in the development of oesophageal squamous cell carcinoma in the UK, where the tumour is relatively uncommon. The polymerase chain reaction was used to examine frozen tissue from 22 oesophageal squamous cell carcinomas for the presence of specific DNA sequences from oncogenic strains of HPV. PCR products were further analysed by Southern blot hybridization. No HPV sequences were detected in any tumours. These results suggest that these types of HPV are not associated with oesophageal squamous cell carcinoma in this country. It is unlikely, therefore, that HPV plays a significant role in the pathogenesis of squamous cell carcinoma of the oesophagus in the UK.
Adult↗
Brush cytology in the diagnosis of neoplasia in Barrett's esophagus.
Esophageal cytology may improve sensitivity for the detection of malignancy but can be difficult to interpret in the presence of inflammation. To assess the value of cytology in assessing patients with Barrett's esophagus a retrospective review was performed. One hundred and sixty two patients (87 esophageal/gastroesophageal junction adenocarcinoma, 65 non-dysplastic Barrett's esophagus and 10 dysplastic Barrett's esophagus) had biopsies and brushings taken for histological and cytological assessment. Eighty two of 92 patients with carcinoma or high-grade dysplasia had true positive malignant cytology. Seven of 65 patients with non-dysplastic but inflamed Barrett's esophagus had false positive malignant cytology. One of these patients had an esophagectomy on the basis of cytology but no tumor was found in the resection specimen. This translates into an 89% sensitivity and specificity of cytology for the detection of esophageal columnar neoplasia. Cytology from Barrett's esophagus can be misleading in the presence of severe inflammation. Cells from a benign Barrett's ulcer may appear frankly malignant when examined in isolation. Esophagectomy should not be performed on the basis of cytological evidence alone.
Adenocarcinoma↗
Photothermal laser ablation of Barrett's oesophagus: endoscopic and histological evidence of squamous re-epithelialisation.
BACKGROUND: Barrett's oesophagus is acquired by severe gastro-oesophageal reflux and is a premalignant condition. Acid suppression or anti-reflux surgery alone do not cause significant regression of the metaplastic mucosa nor reduce the malignant potential. Recent reports have suggested that the combination of mucosal ablation with acid suppression may result in squamous regeneration. AIMS: To destroy Barrett's mucosa by thermal ablation (in the setting of acid suppression) and so induce squamous regeneration. PATIENTS: Sixteen patients with non-dysplastic Barrett's oesophagus were recruited from a surveillance programme. All had been on a proton pump inhibitor. METHODS: At intervals, non-circumferential areas of columnar mucosa were ablated using the KTP laser. Acid suppression was obtained with 40 mg omeprazole daily. Multiple biopsy specimens were obtained for histological examination from ablated areas. RESULTS: Ablation of all areas of glandular mucosa resulted in squamous regeneration. The number of treatments required depended on the length of the Barrett's segment. In 11 patients there was evidence of squamous regeneration over remaining Barrett's glands (in some of the post-treatment biopsy specimens) whilst in nine patients squamous metaplasia was seen within Barrett's glands. CONCLUSION: Mucosal ablation of Barrett's oesophagus by laser, in the setting of acid suppression, results in squamous regeneration (though some burying of Barrett's glands did occur).
Adult↗
Does hospital mortality rate reflect quality of care on a surgical unit?
All deaths occurring in 1 year in the surgical unit of a district general hospital were analysed to determine to what extent crude mortality rates reflect the quality of care. There were 166 deaths, 70% of patients were aged 75 years and older, and 87.3% were emergency admissions. Almost one-half (46.4%) of the deaths were inevitable. This high proportion of inevitable deaths means that crude hospital mortality rates are a poor indicator of the quality of surgical care. Factors such as the nature of the catchment area served, the proportion of emergency versus elective admissions, the numbers of complex operations performed and the availability of convalescent or hospice facilities are a greater influence on surgical mortality rates than variations in the standard of surgical care. The use of crude hospital mortality rates to compare the quality of care given by surgical units should be discontinued as it is unreliable and misleading.
Adult↗
Synchronous upper and lower gastrointestinal endoscopy is an effective method of investigating iron-deficiency anaemia.
BACKGROUND: The investigation of iron-deficiency anaemia is often inadequate. Synchronous upper and lower gastrointestinal endoscopy under the same sedative episode (bidirectional endoscopy; BDE) has been proposed for all such patients. METHODS: The value of this strategy has been examined prospectively. Eighty-nine patients with iron-deficiency anaemia underwent BDE using local anaesthesia of the throat and intravenous midazolam. RESULTS: A cause for gastrointestinal blood loss was found in 75 patients (84 per cent) after BDE alone. Twenty-five patients (28 per cent) had upper gastrointestinal pathology alone, 24 (27 per cent) had lower gastrointestinal pathology alone and 26 (29 per cent) had dual pathology. Forty-five patients (51 per cent) had gastrointestinal malignancy. Twenty patients (22 per cent) had further investigations and these yielded a diagnosis in five. No cause for the anaemia was found in nine patients (10 per cent). Treatment of the bleeding source(s) resolved the anaemia in all but one patient. CONCLUSION: BDE is an effective investigation for patients with iron-deficiency anaemia and its use should be encouraged.
Adult↗
Conservative treatment versus antireflux surgery in Barrett's oesophagus: long-term results of a prospective study.
Explore the source record for details and available documents.
Barrett Esophagus↗
c-erbB-2 overexpression in the dysplasia/carcinoma sequence of Barrett's oesophagus.
AIMS--To investigate overexpression of the oncoprotein c-erbB-2 in the dysplasia/carcinoma sequence of Barrett's columnar-lined oesophagus (CLO). METHODS--Immunohistochemical staining was performed using the monoclonal antibody NCL-CB-11 on formalin fixed tissue from 31 cases of Barrett's carcinoma, 20 cases of cancer associated dysplastic CLO, seven cases of dysplastic CLO without cancer, and 20 cases of non-dysplastic CLO. Membranous staining was regarded as positive for c-erbB-2 overexpression; cytoplasmic staining was recorded separately as its significance is uncertain. RESULTS--Membranous c-erbB-2 overexpression was observed in eight of 31 (26%) carcinomas and in none of the cases of dysplastic CLO. Variable cytoplasmic staining was seen in four of 31 (13%) tumours and seven of 27 (26%) cases of dysplastic CLO. No staining was observed in non-dysplastic CLO. CONCLUSIONS--C-erbB-2 overexpression is a relatively late event in the development of some Barrett's carcinomas and is unlikely to be involved in the early stages of neoplastic transformation of CLO.
Adenocarcinoma↗
Barrett's esophagus.
Explore the source record for details and available documents.
Barrett Esophagus↗
Adenocarcinoma arising in Barrett's oesophagus: evidence for the participation of p53 dysfunction in the dysplasia/carcinoma sequence.
Adenocarcinoma arising in Barrett's oesophagus is often preceded by mucosal dysplasia, but little is currently known about the aetiology or natural history of this dysplasia/carcinoma sequence. To investigate the participation of the tumour suppressor gene p53 in this sequence, an immunohistochemical analysis of p53 protein overexpression, which is known to closely correlate with point mutation of the p53 gene, was conducted in 30 patients with Barrett's adenocarcinoma. Adjacent Barrett's mucosa was dysplastic in 21 (70%) patients. Sixteen (53%) tumours overexpressed p53, 10 of which had adjacent dysplastic Barrett's mucosa. In all 10 patients, this dysplastic mucosa also overexpressed p53, predominantly in areas of high grade compared with low grade dysplasia. In contrast, none of the dysplastic mucosa adjacent to 11 tumours lacking p53 overexpression showed detectable values of p53. These results suggest that p53 dysfunction may participate in the progression from dysplasia to carcinoma in some patients with Barrett's oesophagus.
Adenocarcinoma↗
Should rubber band ligation of haemorrhoids be performed at the initial outpatient visit?
Despite careful technique, a proportion of patients undergoing rubber band ligation (RBL) of haemorrhoids will experience pain or discomfort. To investigate this, a group of 52 unselected patients presenting to the surgical outpatient clinic of Bristol Royal Infirmary were entered into a prospective study using questionnaires, of which 50 (96%) replied. Pain and discomfort were scored on a 10 cm visual analogue scale. Of these patients, 42 (84%) reported pain in the first 24 h; this was moderate to severe in 9 (18%); 30 (60%) had pain in the second 24 h, with 7 (14%) patients suffering moderate to severe pain. In all, 14 (28%) patients were unable to perform their normal activities on the day of treatment and a further 14 (28%) patients felt faint immediately after RBL. The results of this study indicate that pain after RBL occurs more often than previously recognised. It is suggested that informed consent be obtained before RBL and that patients should be given the opportunity to delay treatment if they so wish.
Activities of Daily Living↗
Need to measure outcome after discharge in surgical audit.
OBJECTIVE: To assess the accuracy of outcome data on appendicectomy routinely collected as part of a surgical audit and to investigate outcome in the non-audited period after discharge. DESIGN: Retrospective analysis of audit data recorded by the Medical Data Index (MDI) computer system for all patients undergoing emergency appendicectomy in one year; subsequent analysis of their hospital notes and notes held by their general practitioners for patients identified by a questionnaire who had consulted their general practitioner for a wound complication. SETTING: One district general hospital with four consultant general surgeons serving a population of 250,000. PATIENTS: 230 patients undergoing emergency appendicectomy during 1989. MAIN MEASURES: Comparison of postoperative complications recorded in hospital notes with those recorded by the MDI system and with those recorded by patients' general practitioners after discharge. RESULTS: Of the 230 patients, 29 (13%) had a postoperative complication recorded in their hospital notes, but only 14 (6%) patients had these recorded by the MDI system. 189 (82%) of the patients completed the outcome questionnaire after discharge. The number of wound infections as recorded by the MDI system, the hospital notes, and notes held by targeted patients' general practitioners were three (1%), eight (3%), and 18 (8%) respectively. None of 12 readmissions with complications identified by the hospital notes were identified by the MDI system. CONCLUSIONS: Accurate audit of postoperative complications must be extended to the period after discharge. Computerised audit systems must be able to relate readmissions to specific previous admissions.
Appendectomy↗