Long term results of surgery for early gastric cancer (Br J Surg 2002; 89: 1035-1042).
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Humans↗
Biomedical subjects
P McCulloch
Publications and source records attributed to P McCulloch.
Marimastat as maintenance therapy for patients with advanced gastric cancer: a randomised trial.
This randomised, double-blind, placebo-controlled study was designed to evaluate the ability of the orally administered matrix metalloproteinase inhibitor, marimastat, to prolong survival in patients with non-resectable gastric and gastro-oesophageal adenocarcinoma. Three hundred and sixty-nine patients with histological proof of adenocarcinoma, who had received no more than a single regimen of 5-fluorouracil-based chemotherapy, were randomised to receive either marimastat (10 mg b.d.) or placebo. Patients were treated for as long as was tolerable. The primary endpoint was overall survival with secondary endpoints of time to disease progression and quality of life. At the point of protocol-defined study completion (85% mortality in the placebo arm) there was a modest difference in survival in the intention-to-treat population in favour of marimastat (P=0.07 log-rank test, hazard ratio=1.23 (95% confidence interval 0.98-1.55)). This survival benefit was maintained over a further 2 years of follow-up (P=0.024, hazard ratio=1.27 (1.03-1.57)). The median survival was 138 days for placebo and 160 days for marimastat, with 2-year survival of 3% and 9% respectively. A significant survival benefit was identified at study completion in the pre-defined sub-group of 123 patients who had received prior chemotherapy (P=0.045, hazard ratio=1.53 (1.00-2.34)). This benefit increased with 2 years additional follow-up (P=0.006, hazard ratio=1.68 (1.16-2.44)), with 2-year survival of 5% and 18% respectively. Progression-free survival was also significantly longer for patients receiving marimastat compared to placebo (P=0.009, hazard ratio=1.32 (1.07-1.63)). Marimastat treatment was associated with the development of musculoskeletal pain and inflammation. Events of anaemia, abdominal pain, jaundice and weight loss were more common in the placebo arm. This is one of the first demonstrations of a therapeutic benefit for a matrix metalloproteinase inhibitor in cancer patients. The greatest benefit was observed in patients who had previously received chemotherapy. A further randomised study of marimastat in these patients is warranted.
Adenocarcinoma↗
Muscle UCP-3 mRNA levels are elevated in weight loss associated with gastrointestinal adenocarcinoma in humans.
The mitochondrial uncoupling proteins-2 and -3 are putative mediators of thermogenesis and energy expenditure. We measured the mRNA levels of uncoupling proteins-2 and -3 in skeletal muscle from 12 gastrointestinal adenocarcinoma patients, of whom six had stable weight and six had lost 2-18 kg, and from six healthy controls undergoing elective surgery. Uncoupling proteins-3 mRNA levels were significantly higher in the muscle of the cancer patients with weight loss (2.2 +/- 0.47 arbitrary units) compared both with controls (0.39 +/- 0.20) and with cancer patients who had not lost weight (0.47 +/- 0.23; P<0.02). Uncoupling proteins-2 mRNA levels did not differ significantly between groups. Elevations in muscle uncoupling proteins-3 activity may enhance energy expenditure and this in turn could contribute to tissue catabolism.
Adenocarcinoma↗
Completeness of data entry in three cancer surgery databases.
AIMS: Clinical databases are regularly used for audit and research purposes. The accuracy of data input is critical to the value of these tools, but little is known about the factors which influence the completeness of data recording. The aim of this study was to evaluate the influences affecting completeness of data recording in computerized clinical databases of cancer treatment. METHODS: Data omission rates in three databases dealing with management of breast, colorectal and gastro-oesophageal cancers were calculated. The effects of (a) type of record; (b) nature of data and (c) training required to interpret data were evaluated by univariate and multivariate analyses. RESULTS: The overall data omission rate was 21.9% (upper GI 27.6%, breast 19.6%, colorectal 32.7%, P=0.13). For different categories of data, omission rates varied from 0% to 55%. Fields requiring a 'text field' or 'numerical' entry, or containing demographic data, data required for the process of care or data which required no interpretation were associated with low omission rates. Clinical data, and fields requiring a 'yes/no' response were associated with high omission rates (45 and 48% respectively). Clinical data and data relating to patient demographic details were independently associated with high and low omission rates respectively (odds ratios for significant missing data 86.9 and 1 respectively). CONCLUSION: Clinical data are poorly captured by current cancer surgery databases. Reasons for the poor completion of fields requiring input by clinical staff, particularly availability of time and training, and prioritization of work, should be addressed. Re-design of databases to ensure that data entry is simple and unambiguous may improve accuracy.
Breast Neoplasms↗
How I do it: D2 gastrectomy.
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Anastomosis, Roux-en-Y↗
ASCOT: a comprehensive clinical database for gastro-oesophageal cancer surgery.
We report the development of a multicentre prospective database for gastro-oesophageal cancer surgery. The ASCOT project aims to collect detailed prospective data on co-morbidity, surgery, stage and outcome in a large cohort of patients from a wide variety of hospitals in the UK. We describe the rationale for the initiative, the process of defining the dataset, the database software and structure, the system for data recording and retrieval and the operating rules of the ASCOT co-operative group. Thirty Trusts are currently submitting data, and the first 1000 cases have now been entered. A first annual report has been produced, showing anonymized comparative figures for patient characteristics and outcomes of interest, and a second is due shortly. The collection of detailed comparable data, including co-morbidity evaluation, on a large scale is likely to prove valuable for unit specialist accreditation, surgeon re-validation, audit and research.
Cohort Studies↗
Radiographic clues for high-energy trauma: three cases of sternoclavicular dislocation.
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Accidents, Traffic↗
Laparoscopic staging of gastric cancer is safe and affects treatment strategy.
The accuracy of laparoscopic staging has been documented, but its safety and impact on clinical decision making are less clear. In a prospective series of 64 patients referred to a single consultant, laparoscopy was performed in 49, after exclusion of patients unlikely to derive benefit from laparoscopic staging. The prelaparoscopy treatment plan was altered in 17 (34%). Laparoscopy detected 11 cases of peritoneal and four cases of liver metastasis, of which nine and two, respectively, were not detected by CT scan. Laparoscopy was useful in assessing fitness for major surgery, the planned extent of which was reduced in five cases as a result. Port site metastasis occurred in one case of stage IVB cancer, in conjunction with widespread progressive disease. Laparoscopic staging is recommended in gastric cancer, since it causes important changes to the management plan in one-third of cases, and the risks of port site metastasis appear low.
Adenocarcinoma↗
Can we improve the uptake of gastroscopy in the population at risk for gastric cancer? The effect of home letter information.
The poor outlook for gastric cancer in Britain is largely due to late diagnosis. Earlier diagnosis will require both easy access to endoscopy and increased public awareness of dyspeptic symptoms. We used information by personal letter to encourage reporting of potentially significant symptoms in patients over 40 years of age. The aim of this study was to measure the acceptability and effect on gastroscopy rates of home letter information. Patients over 40 registered with 12 general practices were used in the study (practice population 80,000). Patients over 40 from another nine practices (practice population 46,500) acted as controls. A letter encouraging consultation for new dyspeptic symptoms was sent to all study subjects. Gastroscopy rates were compared in both study and control populations. Questionnaires on symptoms were sent to 500 study subjects. The principal outcome measure was the gastroscopy rate in people over 40 in both populations, before and during the intervention. The gastroscopy rate was 23% higher in the study than in the control population during the study (3.32 vs. 2.7%, P = 0.00016, chi 2 = 14.25). Gastroscopy uptake increased by 85% from 1991/2 to 1993/4 in the study group and by 34% in the control group (chi 2 = 14.02, P = 0.00018). Thirty-one per cent of questionnaire respondents had dyspeptic symptoms; only 3% had 'significant' symptoms of between 2 and 52 weeks duration. Home letters are an acceptable and efficient method of increasing gastroscopy uptake in dyspeptic patients over 40.
Adult↗
c-erbB2 and p53 expression are not associated with stage progression of gastric cancer in Britain or Japan.
The results of surgical treatment for gastric cancer are apparently better in Japan than in Western countries. It has been proposed that this is because of a biological difference between the tumours in Japan and in the West. We have previously reported very similar frequencies of positive immunohistochemical staining for the c-erbB2 oncogene and mutant p53 proteins in British and Japanese gastric cancers, findings which do not seem to support the 'biological difference' hypothesis. We realized that these studies did not rule out differences in the mechanism of cancer progression which might show themselves by a different association between p53 and c-erbB2 expression and stage in the two populations. We therefore re-analysed our data to look for differences in the frequency of p53 and c-erbB2 expression in the British and Japanese populations. Comparison of fixed tissue from 88 British and 89 Japanese tumours showed no significant association of c-erbB2 or p53 with stage progression in either population. Logistic regression showed no difference between the two populations in the relationship between stage and oncogene expression. These results do not support the idea of biologically different cancers in Japan and Britain. Other possible explanations for the difference in results such as the stage migration effect, better efficacy of Japanese-style surgery, or a difference in the host resistance to cancer in the two countries should be considered.
Humans↗
Preliminary results of the use of intraperitoneal carbon-adsorbed mitomycin C in intra-abdominal malignancy.
Eleven patients suffering from intra-abdominal malignancy were treated with various doses of intraperitoneal mitomycin C adsorbed onto activated carbon particles. Seven of the patients underwent resection of their primary gastric tumour and all developed potentially life-threatening severe complications that proved to be fatal in four patients. The pattern of complications seen in these patients was unusual in patients undergoing gastrectomy and must be presumed to be secondary to the intraperitoneal mitomycin C. Intraperitoneal mitomycin C at a dose of 25 mg and 50 mg in the presence of an anastomosis or other suture line does not appear to be safe.
Adenocarcinoma↗
Emergency admission of patients to general surgical beds: attitudes of general practitioners, surgical trainees, and consultants in Liverpool, UK.
OBJECTIVES: To determine (a) whether doctors involved in the process of emergency surgical admission could agree about which patients should be admitted, (b) whether there were consistent differences between doctors in different specialty groups, and (c) whether these opinions were greatly influenced by non-clinical factors. DESIGN: Independent assessment of summarised case histories by three "expert" clinicians (two consultant surgeons and one general practitioner (GP)), by a group of 10 GPs, and by a group of 10 junior and senior surgeons. Experts, but not other observers, scored admissions both independently and as a consensus group. Observers indicated for each patient whether they would admit, would not admit, or were unsure. SETTING: An urban general hospital with teaching status. SUBJECTS: Fifty consecutive patients admitted to the general surgical unit as emergencies during 1995. MAIN OUTCOME MEASURES: Proportion of admissions considered unnecessary or uncertain: agreement between observers on these proportions: effect of social and procedural factors on the admission decision. RESULTS: Between 8 and 34% of admissions were considered unnecessary and 20-38% of unclear necessity. Agreement between the groups of clinicians was not good. GPs and consultant surgeons showed the poorest agreement (kappa = 0.08 to 0.25, 4 comparisons), and the GPs scored a higher percentage of admissions as unnecessary (34 v 8-12%). After discussion, the consensus group achieved good to very good agreement (kappa 0.61-0.84). CONCLUSIONS: Different groups of doctors vary widely in their views about the need for emergency surgical admission. Good agreement can be reached by consensus discussion. GPs are less likely than surgeons to consider emergency surgical admission necessary.
Attitude of Health Personnel↗
Surgical practice is evidence based.
BACKGROUND: The quality of surgical research, and particularly the reluctance of surgeons to perform randomized controlled trials, has been criticized. The proportion of surgical treatments supported by satisfactory scientific evidence has not been evaluated previously. METHODS: A 1-month prospective audit was performed of 100 surgical inpatients admitted under two consultants in a general surgical/vascular unit at an urban teaching hospital; the main illness and interventions were agreed through group discussions in each case. The literature concerning the efficacy of each treatment was reviewed, and the evidence was categorized as: (1) supported by randomized controlled trial evidence; (2) sufficient other evidence of efficacy to make a placebo-controlled trial unethical; or (3) neither of the above. RESULTS: Of the 100 patients studied, 95 (95 per cent confidence interval (c.i.) 89-98) received treatment based on satisfactory evidence (categories 1 and 2) and, of these, 24 patients (95 per cent c.i. 17-35) received treatments based on randomized controlled trial evidence and 71 had treatments based on other convincing evidence (95 per cent c.i. 62-80). CONCLUSION: Inpatient general surgery is 'evidence based', but the proportion of surgical treatments supported by randomized controlled trial evidence is much smaller than that found in general medicine. Some reasons for this are clear, but the extent to which surgical practice needs to be reevaluated is not. Current methods for classifying and describing evidence in therapeutic studies need improvement.
Emergencies↗
Randomized clinical trial of breast irradiation following lumpectomy and axillary dissection for node-negative breast cancer: an update. Ontario Clinical Oncology Group.
BACKGROUND: Breast-conservation surgery is now commonly used to treat breast cancer. Postoperative breast irradiation reduces cancer recurrence in the breast. There is still controversy concerning the necessity of irradiation of the breast in all patients. PURPOSE: We present an update of results from a randomized clinical trial designed to examine the efficacy of breast irradiation following conservation surgery in the treatment of women with axillary lymph node-negative breast cancer. The patients were enrolled from April 1984 through February 1989. Initial results were published in 1992 after a median follow-up time of 43 months. It was reported that recurrence of cancer in the breast occurred in 5.5% of the patients who received breast irradiation compared with 25.7% of those who did not. No difference in survival was detected between the two treatment groups. Now that the median patient follow-up has reached 7.6 years, the trial end points have been re-examined and an attempt has again been made to identify a group of patients at low risk for recurrence of cancer in the breast. METHODS: Eight hundred thirty-seven patients with node-negative breast cancer were randomly assigned to receive either radiation therapy (n = 416) or no radiation therapy (n = 421) following lumpectomy and axillary lymph node dissection. The cumulative local recurrence rate as a first event, distant recurrence (i.e., occurrence of metastasis) rate, and overall mortality rate for the treatment groups were described by the Kaplan-Meier method and compared with the use of the logrank test. The Cox proportional hazards model was used to adjust the observed treatment effect for the influence of various prognostic factors (patient age, tumor size, estrogen receptor level, and tumor histology) at study entry on the outcomes of local breast recurrence, distant recurrence, and overall mortality. All P values resulted from the use of two-tailed statistical tests. RESULTS: One hundred forty eight (35%) of the nonirradiated patients and 47 (11%) of the irradiated patients developed recurrent cancer in the breast (relative risk for patients in the former versus the latter group = 4.0; 95% confidence interval = 2.83-5.65; P < .0001). Ninety-nine (24%) of the patients in the former group have died compared with 87 (21%) in the latter group. Age (< 50 years), tumor size (> 2 cm), and tumor nuclear grade (poor) continued to be important predictors for local breast relapse. On the basis of these factors, we were unable to identify a subgroup of patients with a very low risk for local breast cancer recurrence. Tumor nuclear grade, as previously reported, and tumor size were important predictors for mortality. CONCLUSIONS: Breast irradiation was shown to reduce cancer recurrence in the breast, but there was no statistically significant reduction in mortality. A subgroup of patients with a very low risk for local breast recurrence who might not require radiation therapy was not identified.
Adult↗
D2 gastrectomy: lessons from a prospective audit of the learning curve.
A 3-year prospective study of the learning curve for D2 gastrectomy was carried out by one surgeon beginning to perform the operation independently after intensive specialist training. Some 38 patients were treated; there were four postoperative deaths and 22 patients had complications. Postoperative morbidity decreased significantly with time (rS = -0.38, P = 0.02, 95 per cent confidence interval -0.62 to -0.07). The physiological component of POSSUM (Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity) was significantly lower in the third year (median value 15, 16 and 14 for years 1, 2 and 3, n = 31, chi 2 = 7.5, 2 d.f., P = 0.02, Kruskal-Wallis test), but the operative POSSUM scores and the number of lymph nodes found were not decreased (median operative POSSUM score 19, 18 and 21, n = 31, chi 2 = 0.2, 2 d.f., P = 0.91, Kruskal-Wallis test). The results suggest a learning curve lasting about 18-24 months or 15 to 25 procedures before a plateau is reached. Improved results were associated with changes in case selection and operative tactics but not with reduced extent of lymphadenectomy. D2 gastrectomy should be restricted to specialist centres where adequate training and supervision can be provided during the learning curve.
Female↗
Quantification of angiogenesis in solid human tumours: an international consensus on the methodology and criteria of evaluation.
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Animals↗