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Biomedical subjects

J W Fielding

Publications and source records attributed to J W Fielding.

At least 19 recordsLinked to original sources

Radical surgery for early gastric cancer.

The role of radical surgery for early gastric cancer has become a topic of considerable debate. Despite excellent results from Japan and several retrospective and uncontrolled trials, results from two large prospective randomized trials appear to demonstrate no benefit from D2 compared to the D1 resections. These trials have prompted a move away from radical lymph-node dissection. We argue that this reasoning is flawed and based not on the lack of efficacy of the D2 resection but in an attempt to reduce post-operative mortality and morbidity. Post-operative complications are largely a result of distal pancreatectomy and splenectomy and the relative inexperience of surgeons performing the operations. By preserving these organs and concentrating surgery to specialized centres the complication rate of radical surgery can be significantly reduced to approximate that of non-radical surgery. Lymph-node metastasis to the N2 nodes in early gastric cancer has been shown to be as high as 23%. Non-radical surgery poses significant risks of leaving residual disease. Radical surgery must remain the operation of choice if non-curative surgery for a curable condition is to be avoided.

Gastrectomy

Screening for gastric cancer by Helicobacter pylori serology: a retrospective study.

BACKGROUND: Screening by serology for Helicobacter pylori in young dyspeptic patients has been shown to be effective in reducing demand for endoscopy. H. pylori has been implicated in the causation of gastric cancer and the reported seropositivity rate in patients with gastric cancer ranges from 69 to 94 per cent. The aim of this study was to assess the potential value of Helicobacter antibodies as a method of selecting dyspeptic patients over the age of 45 years for endoscopy. METHODS: A retrospective comparison of the antibody status to H. pylori was made between 154 patients with gastric cancer and a sex- and date of birth-matched dyspeptic control group. Results from the former group were correlated with demographic data and tumour characteristics. RESULTS: Significantly more patients with gastric cancer were seropositive than controls (77 versus 66 per cent). H. pylori was not related to the Laurén classification of the tumour. Tumour site was significant: body and antrum tumours were associated with Helicobacter whereas cardial tumours appeared to be unrelated. CONCLUSION: Screening by antibody assays to H. pylori would miss more than 30 per cent of current gastric cancers. The increasing incidence of cardial cancer would cause this percentage to rise in the future.

Adult

Machine learning techniques in early screening for gastric and oesophageal cancer.

A database on 2692 dyspeptic patients over the age of 40 was established, consisting of 73 epidemiological and clinical variables. A tree-based machine learning algorithm (PREDICTOR) was applied to this database, in order to attempt to find rules which would classify patients into 2 groups, i.e., those suffering from gastric or oesophageal cancer, and the remainder. The results were encouraging. The cross-validated classification performance figure showed that by classifying 61.3% of the patients as high risk, a sensitivity of 94.9% and a specificity of 39.8% could be achieved. It is planned to construct an expert system based on the rules produced by the machine learning algorithm, in order to provide preliminary screening for cancer in dyspeptic patients.

Algorithms

Vulvoperineal reconstruction after excision of anogenital multifocal intraepithelial neoplasia ("MIN").

Over the past 7 years, 12 women have been treated utilising a radical surgical approach for extensive vulval involvement as a component of multifocal intraepithelial neoplasia (MIN) of the female genital tract. The patients were analysed with respect to the anatomical site of involvement, age, presenting complaints and their duration, colposcopic examination, histopathology and surgical treatment. Gynaecologists, general surgeons and plastic surgeons were involved in the surgical treatment which was an initial colostomy followed by a definitive vulvoperineal resection and simultaneous vulval reconstruction using meshed split skin grafts or a combination of skin grafts and local flaps. 17 vulvoperineal reconstructions were done for 12 patients. Three had an incomplete histopathological clearance at the initial operation. Apart from these three patients, one had recurrence of symptoms alone, without any evidence of MIN, which was possibly due to human papilloma virus infection. One patient developed malignant squamous invasion 4 years later, which was cured with surgical excision and reconstruction. Colostomy closure was done after achieving local control of the disease. This staged approach does achieve the objectives of eliminating disease and alleviating symptoms. It preserves function and attempts to reconstruct normal anatomy without compromising the principles of surgical oncology and results in a high patient satisfaction.

Adult

The influence of age on the surgical management of carcinoma of the stomach.

The medical records of 31,808 patients with gastric cancer registered with the West-Midlands Cancer Registry between 1957-1981 were reviewed to determine the influence of age on presentation, stage assessment, management, survival and mortality rates. When analysed by stage, and excluding post-operative deaths, survival was similar in all age groups. This study confirms stage of disease to be the single most important prognostic factor. The inverse relationship between laparotomy and age implies inadequate assessment of stage in the elderly. The poor prognosis in unresected cases suggests that increased precise staging by laparotomy or laparoscopy will have minimal adverse effects. On the other hand this may result in increased resections and survival.

Age Factors

Expression of proliferating cell nuclear antigen (PCNA) in gastric carcinoma: no evidence for prognostic value.

It has been proposed that immunostaining with PC10, a monoclonal antibody against proliferating cell nuclear antigen (PCNA), is of prognostic value in gastric carcinoma. Gastric carcinomas from a series of 90 patients in whom survival data were known have been studied. There was no relation between the degree of PC10 immunostaining assessed semiquantitatively and survival.

Adenocarcinoma

Evaluation of pepsinogen A and gastrin-17 as markers of gastric cancer and high-risk pathologic conditions.

BACKGROUND: Gastric cancer remains a major cause of mortality and will remain so for the lifetime of current clinicians. Many cancers are diagnosed at a stage when current therapy cannot provide the hope of cure. A method for early detection of gastric cancer which can be widely applied is needed. The serum levels of pepsinogen A and gastrin-17 have been shown to vary in the presence of pathologic conditions of the gastric mucosa and may provide such a tool. METHODS: Serum samples were obtained from 432 patients undergoing endoscopy for undiagnosed dyspepsia. The levels of pepsinogen I and gastrin-17 were estimated by radioimmunoassay and compared with the final diagnosis. Discriminant analysis was performed to assess the value of the peptides predicting the presence of gastric cancer and the high-risk mucosal changes. RESULTS: Abnormal levels of gastrin-17 or pepsinogen A were found in 60% of patients with gastric cancer and 60% of those with one of the high-risk mucosal changes, the latter figure rising to 75% when the changes were in the upper third of the stomach. Discriminant analysis showed the log of gastrin-17 and log of pepsinogen A to be the best predictors of the high-risk mucosal changes, gastric cancer, and benign disease. CONCLUSIONS: These results confirm gastrin-17 and pepsinogen A as markers of pathologic gastric conditions and suggest that these peptides are potential screening tools worthy of further assessment.

Adult

Resection-line involvement in gastric cancer: a continuing problem.

Surgeons are aware of the adverse effect that resection-line disease has on anastomotic leakage, perioperative mortality and long-term survival. In an attempt to assess the effect of this knowledge on surgical practice, patients entered into the second British Stomach Cancer Group adjuvant therapy trial were studied. The presence of resection-line disease was compared with the operative stage. Of 555 patients for whom complete data were available, resection-line disease was present in 105 (19 per cent). Of 424 patients undergoing what the surgeon considered to be a potentially curative operation, 55 (13 per cent) had involvement of one or both resection lines, rendering the surgery palliative. Only 9 per cent of patients with stage I-III disease and resection-line involvement survived beyond 5 years, compared with 27 per cent of those with clear lines. Despite knowledge of the adverse effects of resection-line disease, surgeons continue to perform inadequate resections. This demonstrates the need for a more aggressive approach to assessment of resection margins at operation.

Gastrectomy

An evaluation of the effectiveness and safety of razoxane when used as an adjunct to surgery in colo-rectal cancer. Report of a controlled randomised study of 603 patients.

A prospective controlled randomised trial to evaluate the effectiveness and safety of razoxane is reported. Some 603 patients with colo-rectal cancer having curative surgery entered the study, and all have been followed up for a minimum of five years. Statistical analysis showed that razoxane treatment had no effect either beneficial or adverse on the rates of recurrence or on five year survival of patients with colo-rectal cancer. It is possible that a more prolonged course of razoxane might have significantly influenced survival. The incidence of severe adverse reaction was low but it is of concern that one patient developed leukaemia. Should razoxane be considered for future use it is recommended that continuous low dose therapy be given for no longer than 12 months. No renal, hepatic, pulmonary or cardiac toxicity was noted.

Aged

Peri-operative heparin: a possible adjuvant to surgery in colo-rectal cancer?

Analysis of data from a randomised trial of adjuvant razoxane involving 603 patients with colo-rectal cancer having curative surgery is reported. The results show that razoxane was ineffective but peri-operative subcutaneous heparin treatment apparently conferred a statistically significant improvement in survival at 5 years, or equivalently a reduction in the risk of death. This beneficial effect is apparent in both razoxane treated and control patients and is not explained by demonstrable differences between heparin and non-heparin treated patients in the distribution of known prognostic factors. Adjustment for these factors slightly increased the apparent magnitude of the beneficial effect.

Chemotherapy, Adjuvant

Epstein-Barr virus and carcinomas: rare association of the virus with gastric adenocarcinomas.

We have analysed 174 gastric carcinomas from the United Kingdom and from Japan for the presence of Epstein-Barr virus (EBV) using in situ hybridisation for the small EBV-encoded nuclear RNAs (EBERs). EBV was detected in the tumour cells in all of six undifferentiated gastric carcinomas with prominent lymphoid stroma (undifferentiated carcinomas of nasopharyngeal type, UCNT) but only in three of the remaining 168 typical gastric adenocarcinomas (1.8%). No differences were observed between the British and the Japanese cases. One case with an EBV-positive UCNT showed adjacent areas of EBV-negative typical adenocarcinoma. It is uncertain whether these patterns represent two independent carcinomas or whether they are the result of heterogeneous EBV infection in a single tumour. In the remaining EBV-positive carcinomas, viral transcripts were detected in virtually all tumour cells, indicating that EBV infection must have taken place early in the neoplastic process and suggesting that the virus is likely to be of pathogenetic significance for the virus-associated tumours. Immunohistology demonstrated absence of detectable levels of the EBV-encoded latent membrane protein, LMP1, and nuclear antigen, EBNA2. The BZLF1 protein which induces the switch from latent to lytic infection was demonstrated in a small proportion of the tumour cells in three cases. The close association of EBV with undifferentiated gastric carcinomas compared to the variable association with gastric adenocarcinomas suggests fundamentally different roles for the virus in the aetiology of these two malignancies.

Adenocarcinoma

A randomised trial of selective or routine on-table cholangiography.

To assess the value of pre- and peroperative indicators of common bile duct (CBD) stones, 167 patients undergoing cholecystectomy were randomised to receive either routine (R) or selective (S) on-table cholangiography (OTC). In all, 81/84 patients in the R group and 22/78 in the S group had OTCs (P < 0.0001). In the R group 11/81 were positive (one false-positive) and in the S group 7/22 were positive (P < 0.05). CBD stones were present in 10/81 in the R group and 7/78 in the S group (P = NS). In the R group 8/10 and in the S group 5/7 had CBD stones diagnosed preoperatively by ultrasound scanning (USS), giving USS a positive predictive value (PPV) of 100% and a sensitivity of 71.4% in the S group. A raised preoperative alkaline phosphatase (ALP) was found in 1/10 in the R group and 1/7 in the S group (PPV = 33.3%, sensitivity = 14.3%). In the R group 1/10 and in the S group 1/7 (PPV = 25%, sensitivity = 14.3%) were found to have a dilated CBD during operation suggesting CBD stones. There have been no cases of symptomatic unsuspected retained CBD stones during follow-up to date. Our study has demonstrated that selective use of OTCs can be safely employed in open cholecystectomies. Over 85% (6/7 in the S group and 15/17 overall) of CBD stones can be diagnosed preoperatively by USS and liver function tests, with USS having the greatest PPV and sensitivity.

Adult

Acceptability of opportunistic screening for occult gastrointestinal blood loss.

OBJECTIVE: To test patient compliance for faecal occult blood testing in suburban and inner city general practice. DESIGN: Prospective opportunistic trial using the Haemoccult test kit. Tests were offered during routine surgery attendance. SETTING: Three group general practices in Birmingham. SUBJECTS: All patients aged 40 years or older on the start date who routinely attended surgery during two years. MAIN OUTCOME MEASURES: Numbers of patients approached for testing and the numbers refusing, accepting, and returning the test kits. RESULTS: Only 26.3% (1230/4677) of the potential target population had been screened within the two years, although 988 (39.3%) of the suburban practice target were screened. However, 55.7% (1230/2207) of patients actually offered a test returned completed kits, with only 6% (133) refusing the kit. 683 (61.6%) patients aged 50-69 returned kits, compared with 343 (54.3%) aged 70 or over and 204 (43.8%) aged 40-49. These differences were significant (p less than 0.001). Patients from the inner city practice were significantly less likely to be offered the test than those in suburban practice (242 (11.2%) v 988 (39.9%), p less than 0.001) and return the samples (242 (38.8%) v 988 (62.4%), p less than 0.001). Patients from the inner city practice were also more likely to refuse the test (78 (12.5%) v 55 (3.5%), p less than 0.001). CONCLUSIONS: Opportunistic testing for occult faecal blood in asymptomatic patients was reasonably acceptable to patients, especially those in a suburban practice. If the test is shown to reduce mortality from colorectal cancer then formal screening would probably achieve acceptable target rates, especially among patients aged 50-69, who represent the prime risk group.

Adult

The selection of cases for randomised trials: a registry survey of concurrent trial and non-trial patients. The British Stomach Cancer Group.

A randomised trial of adjuvant chemotherapy vs placebo in operable stomach cancer recruited 249 patients from the West Midlands Region between 1976-1980. A Cancer Registry survey identified a further 1261 suitable concurrent cases. Trial patients were compared with the 960 non-trial cases from participating Districts. Only 493 (51%) non-trial cases passed all of the prospective trial selection criteria for entry. Stage and fitness caused the majority of exclusions and were also highly prognostic. A univariate analysis comparing eligible patients with the trial showed the two groups to be balanced for the significant independent prognostic factors of the trial. However, differences in patient age and the surgery performed indicate that recruitment may have been influenced by unknown selection factors. This survey highlights the difficulty of retrospective selection and confirms the need for randomised controls. Data available from specialist Registries may be used to help develop new protocols and to verify and extend trial results.

Adolescent