Biomedical subjects

R J C Steele

Publications and source records attributed to R J C Steele.

17 recordsLinked to original sources

PubMed2007

Artificial neural network: predicted vs observed survival in patients with colonic cancer.

PURPOSE: An Internet-web-based artificial neural network has been developed for practicing clinical oncologists and medical researchers as part of an ongoing program designed for the implementation of advanced neural networks for prognostic estimates and eventually for management/treatment decisions in individual patients with colonic cancer. METHODS: An interdisciplinary team of academic oncologists and physicists has configured and implemented a Partial Logistic Artificial Neural Network and trained it to predict cancer-related survival in patients with confirmed colorectal cancer by using a database (1,558 patients) made available for the study by the Information & Statistics Division of National Health Service Scotland. The reliability of the trained network was evaluated against Kaplan-Meier observed survival plots of a random sample of 300 patients not used in the training but forming part of the same data set. RESULTS: The predicted survival curves obtained as the output from the artificial neural network showed close agreement with observed actual survival rates of a cohort of 300 patients with four grades of risk of dying from the cancer within five years of diagnosis. CONCLUSIONS: The web-based Partial Logistic Artificial Neural Network system accurately predicts survival after staging and treatment of colonic cancer. It can be made web-accessible where it is powerful enough to serve hundreds of users simultaneously.

Aged↗

PubMed2006

Relationship between point gene mutation, chromosomal abnormality, and tumour suppressor gene methylation status in colorectal adenomas.

Epigenetic mechanisms in carcinogenesis may have a significant role in the development of colorectal cancer. To investigate this phenomenon in early-stage disease, promoter methylation status in the tumour suppressor genes APC, MGMT, hMLH1, P14/P14ARF, and CDKN2A/P16 was investigated in 78 colorectal adenomas. These had previously been characterized for mutations of APC, KRAS, and TP53 genes and for chromosomal abnormality by comparative genomic hybridization (CGH). APC hypermethylation was seen in 52 tumours (66.7%). APC showed either methylation or mutation in 66 lesions (84.6%), but these events were not statistically associated. MGMT methylation was detected in 39 cases (50%). Adenomas with this abnormality showed a significantly lower number of chromosomal changes by CGH (p < 0.02), confirming that DNA repair defect of this type is associated with a lower level of chromosomal instability. An hMLH1 methylation defect was seen in only one adenoma (1.3%), from a patient who had a synchronous cancer showing the same defect. Methylation of P14 (P14ARF) was seen in 31 adenomas (39.7%) and CDKN2A (P16) abnormality in 25 (32.1%). DNA methylation at two or more loci was seen in 46 tumours (59%), while 11 lesions (14.1%) showed no evidence of hypermethylation at any of the loci studied. Methylation at any or all of MGMT, P14 or P16 was significantly associated with APC methylation (p = 0.01). Those neoplasms with more than two methylated genes showed significantly fewer chromosomal abnormalities than adenomas with one or no methylated loci (p < 0.001). There was no association between specific individual chromosomal abnormalities, APC, KRAS or TP53 mutations and any pattern of methylation abnormality. We conclude that methylation abnormality is very common in pre-invasive colorectal neoplasia, and that high level methylation is associated with low level chromosomal instability.

Adaptor Proteins, Signal Transducing↗

PubMed2006

Modern challenges in colorectal cancer.

Colorectal cancer is a major problem worldwide and in the United Kingdom it is responsible for some 20,000 deaths per annum. Mortality from the disease is gradually decreasing in developed countries but, in the United Kingdom at least, its incidence is on the increase. In this article the major current challenges in colorectal cancer will be dealt with under the following headings: aetiology and prevention, early detection, diagnosis, surgery, adjuvant therapy and management of advanced disease.

Colorectal Neoplasms↗

PubMed2006

Medications with anticoagulant properties increase the likelihood of a negative colonoscopy in faecal occult blood test population screening.

OBJECTIVE: The aim of this study was to evaluate the effect of medication with anticoagulant properties on the false positive rate in a population-based faecal occult blood test (FOBt) colorectal screening programme. METHODS: Eight hundred and forty-six consecutive individuals found to be FOBt-positive in the Scottish arm of the national colorectal cancer screening pilot were studied. All were aged between 50 and 69 years and underwent colonoscopy. Before the procedure the participants' current medication was recorded, and correlated with the colonoscopic findings. RESULTS: Of 846 participants, 301 (35.6%) were taking regular anticoagulant medication at the time of FOB testing. Of these, 143 (47.5%) had colorectal neoplasia found on colonoscopy, whereas of those not taking anticoagulant medication, 308 (56.5%) were found to have neoplasia. This 9% difference was statistically significant (P = 0.012). CONCLUSION: These results indicate that in a population screened for colorectal neoplasia by FOB testing, anticoagulant medication being taken at the time of testing is associated with an increased likelihood of a negative colonoscopy.

Aged↗

PubMed2005

Rubber band ligation versus excisional haemorrhoidectomy for haemorrhoids.

BACKGROUND: Traditional treatment methods for haemorrhoids fall into two broad groups: less invasive techniques including rubber band ligation (RBL), which tend to produce minimal pain, and the more radical techniques like excisional haemorrhoidectomy (EH), which are inherently more painful. For decades, innovations in the field of haemorrhoidal treatment have centred on modifying the traditional methods to achieve a minimally invasive, less painful procedure and yet with a more sustainable result. The availability of newer techniques has reopened debate on the roles of traditional treatment options for haemorrhoids. OBJECTIVES: To review the efficacy and safety of the two most popular conventional methods of haemorrhoidal treatment, rubber band ligation and excisional haemorrhoidectomy. SEARCH STRATEGY: We searched all the major electronic databases (MEDLINE, EMBASE, CENTRAL, CINAHL). SELECTION CRITERIA: Randomised controlled trials comparing rubber band ligation with excisional haemorrhoidectomy for symptomatic haemorrhoids in adult human patients were included. DATA COLLECTION AND ANALYSIS: We extracted data on to previously designed data extraction sheet. Dichtomous data were presented as relative risk and 95% confidence intervals, and continuous outcomes as weighted mean difference and 95% confidence intervals. MAIN RESULTS: Three trials (of poor methodological quality) met the inclusion criteria. Complete remission of haemorrhoidal symptom was better with EH (three studies, 202 patients, RR 1.68, 95% CI 1.00 to 2.83). There was significant heterogeneity between the studies (I2 = 90.5%; P = 0.0001). Similar analysis based on the grading of haemorrhoids revealed the superiority of EH over RBL for grade III haemorrhoids (prolapse that needs manual reduction) (two trials, 116 patients, RR 1.23, CI 1.04 to 1.45; P = 0.01). However, no significant difference was noticed in grade II haemorrhoids (prolapse that reduces spontaneously on cessation of straining) (one trial, 32 patients, RR 1.07, CI 0.94 to 1.21; P = 0.32) Fewer patients required re-treatment after EH (three trials, RR 0.20 CI 0.09 to 0.40; P < 0.00001). Patients undergoing EH were at significantly higher risk of postoperative pain (three trials, fixed effect; 212 patients, RR 1.94, 95% CI 1.62 to 2.33, P < 0.00001). The overall delayed complication rate showed significant difference (P = 0.03) (three trials, 204 patients, RR 6.32, CI 1.15 to 34.89) between the two interventions. AUTHORS' CONCLUSIONS: The present systematic review confirms the long-term efficacy of EH, at least for grade III haemorrhoids, compared to the less invasive technique of RBL but at the expense of increased pain, higher complications and more time off work. However, despite these disadvantages of EH, patient satisfaction and patient's acceptance of the treatment modalities seems to be similar following both the techniques implying patient's preference for complete long-term cure of symptoms and possibly less concern for minor complications. So, RBL can be adopted as the choice of treatment for grade II haemorrhoids with similar results but with out the side effects of EH while reserving EH for grade III haemorrhoids or recurrence after RBL. More robust study is required to make definitive conclusions.

Hemorrhoids↗

PubMed2005

The prognostic significance of K-ras, p53, and APC mutations in colorectal carcinoma.

BACKGROUND: Accumulation of molecular alterations, including mutations in Kirsten-ras (K-ras), p53, and adenomatous polyposis coli (APC), contribute to colorectal carcinogenesis. Our group has previously characterised a panel of sporadic colorectal adenocarcinomas for mutations in these three genes and has shown that p53 and K-ras mutations rarely occur in the same colorectal tumour. This suggests that mutations in these genes are on separate pathways to colorectal cancer development and may influence patient prognosis independently. AIMS: To correlate the presence or absence of mutations in K-ras, p53, and APC with survival in a cohort of colorectal cancer patients. PATIENTS: A series of 107 inpatients treated surgically for colorectal cancer in Tayside, Scotland between November 1997 and December 1999. METHODS: Colorectal tumours were characterised for mutations in K-ras, p53, and APC. Kaplan-Meier survival curves were constructed using overall survival and disease specific survival as the primary end points. Patient survival was analysed using the log rank test and Cox proportional hazards model. RESULTS: Patients with K-ras mutations had significantly poorer overall survival than patients without K-ras mutations (p = 0.0098). Multivariate analysis correcting for Dukes' stage, age, and sex confirmed this (hazard ratio 2.9 (95% confidence interval 1.4-6.2); p = 0.0040). K-ras mutations were also significantly associated with poorer disease specific survival. The presence of APC and p53 mutations did not affect survival in this cohort of patients (p = 0.9034 and p = 0.8290, respectively). CONCLUSIONS: Our data indicate that the presence of K-ras mutations predicts poor patient prognosis in colorectal cancer, independently of tumour stage.

Adenocarcinoma↗

PubMed2005

Postdefaecation pain syndrome after circular stapled anopexy is abolished by oral nifedipine.

BACKGROUND: Controversy has surrounded the technique of circular stapled anopexy since an isolated report of a high incidence of persistent postdefaecation pain following the procedure. The characteristics, clinical course and management of this complication have not been described. METHODS: Within an ongoing multicentre randomized clinical trial comparing circular stapled anopexy with closed haemorrhoidectomy, 77 patients underwent circular stapled anopexy. Follow-up was at 6, 12, 24 and 48 weeks. Patients underwent transanal ultrasonography, anal electrosensitivity testing and manometry. RESULTS: Of the 77 patients who had circular stapled anopexy, three men reported new-onset postdefaecation pain that compromised lifestyle, including ability to return to work. All three had sphincter hypertonicity on digital and manometric examination but were refractory to topical 0.2 per cent glyceryl trinitrate ointment. The addition of oral nifedipine 20 mg twice daily did not alter anal sphincter pressures but rapidly abolished symptoms and restored quality of life. CONCLUSION: Postdefaecation pain is a specific complication of circular stapled anopexy, affecting a small percentage of patients. Men with a high anal sphincter pressure appear to be at risk. Although the exact aetiology remains unclear, it is likely that rectal rather than anal sphincter muscle is affected. Oral nifedipine represents an effective therapy.

Adult↗

PubMed2005

Lower gastrointestinal symptoms are not predictive of colorectal neoplasia in a faecal occult blood screen-positive population.

BACKGROUND: The aim of this study was to evaluate the incidence of lower gastrointestinal symptoms in faecal occult blood (FOB) test-positive participants in a colorectal screening programme, and to compare the colonoscopic findings in symptomatic and asymptomatic individuals. METHODS: Five hundred and sixty-three consecutive individuals with a positive FOB test in the Scottish arm of the national colorectal cancer screening pilot were studied. All were aged between 50 and 69 years and underwent colonoscopy. Before the procedure the participants were given a standard questionnaire to elicit gastrointestinal symptoms; these were correlated with the colonoscopic findings. RESULTS: Of the 563 participants, 439 (78.0 per cent) had one or more lower gastrointestinal symptoms and 124 (22.0 per cent) were symptom free. Taking adenoma and carcinoma together, 322 (57.2 per cent) of the subjects were found to have colorectal neoplasia, and 128 (22.7 per cent) had a completely normal colon. Rectal bleeding was the most common symptom, followed by change in bowel habit, abdominal pain, tenesmus, unexplained weight loss, rectal pain and unexplained anaemia. No significant associations were found between any of these symptoms and the findings at colonoscopy. CONCLUSION: In a FOB test-positive screened population, lower gastrointestinal symptoms are common, but are not predictive of colorectal neoplasia.

Abdominal Pain↗

PubMed2005

Systematic review of randomized trials comparing rubber band ligation with excisional haemorrhoidectomy.

BACKGROUND AND METHOD: This review compares the two most popular treatments for haemorrhoids, namely rubber band ligation (RBL) and excisional haemorrhoidectomy. Randomized trials were identified from the major electronic databases. Symptom control, retreatment, postoperative pain, complications, time off work and patient satisfaction were assessed. Relative risk (RR) and weighted mean difference with 95 per cent confidence interval (c.i.) were estimated using a random-effects model for dichotomous and continuous outcomes respectively. RESULTS: Three trials met the inclusion criteria and all were of poor methodological quality. Complete remission of haemorrhoidal symptoms was better after haemorrhoidectomy (RR 1.68 (95 per cent c.i 1.00 to 2.83)). There was significant heterogeneity between the studies (I(2) = 90.5 per cent; P < 0.001). Fewer patients required retreatment after haemorrhoidectomy (RR 0.20 (95 per cent c.i 0.09 to 0.40)), but anal stenosis, postoperative haemorrhage and incontinence to flatus were more common with this operation. CONCLUSIONS: Haemorrhoidectomy produced better long-term symptom control in patients with grade III haemorrhoids, but was associated with more postoperative complications than RBL.

Hemorrhoids↗

PubMed2005

P53 in cancer: a paradigm for modern management of cancer.

The p53 tumour suppressor gene is thought to be central in protecting against the development of cancer, and this article reviews current understanding of its function and potential clinical significance. Information for this review was obtained from previous review articles, references cited in original papers, a Pubmed search of the last twelve months' literature and by scanning the latest issues of relevant journals. P53 can be described as a stress response gene, its product (the p53 protein) acting to induce apoptosis or cell-cycle arrest in response to DNA damage, thereby maintaining genetic stability in the organism. These functions are realised by a series of steps known as the "p53 pathway" involving induction of the expression of a number of other genes. As p53 is the most commonly mutated gene in human cancer, it has attracted a great deal of interest in the areas of prognosis, diagnosis and therapy, and p53 gene therapy is becoming established as a useful adjunct to conventional cancer treatment.

Gene Expression Regulation, Neoplastic↗

PubMed2005

SELDI-TOF proteomic analysis and cancer detection.

BACKGROUND: In recent years proteomic approaches have been widely used to diagnose disease and the new technology of surface enhanced laser-desorption and ionization time-of-flight mass spectrometry (SELDI-TOF MS) is very promising. METHODS: A review of English language literature was undertaken using Internet databases such as PubMed and Medline for studies using proteomic technologies for the early detection of cancer. RESULTS: SELDI-TOF is an array based mass spectrometric method in which proteins of interest are selectively absorbed onto a chemically modified surface and the mass and amount of each protein is measured by irradiating the surface with a laser and measuring the time-of-flight. The technology has revealed a large number of previously uncharacterized biomarkers for a wide variety of cancers. Its versatility has also been demonstrated by its application as a tool for mining a wide variety of biological tissues and fluids. CONCLUSIONS: The majority of these studies have discriminated between diseased and healthy controls with a high degree of sensitivity and specificity. The reproducibility, standardization and feasibility of this technology need to be addressed before these proteomic approaches to the discovery of novel, highly sensitive diagnostic tools can become routine clinical care.

Biomarkers, Tumor↗

PubMed2003

Anastomotic recurrence of rectal adenoma after anterior resection.

Transanal local excision of posterior benign rectal tumors is usually safe. Here, we report a case of transanal excision of a posterior anastomotic recurrence of a rectal adenoma after a stapled anterior resection that resulted in perforation into the peritoneal cavity.

Adenoma, Villous↗

PubMed2003

Attributes of trainers for postgraduate training in general surgery--a national consensus.

BACKGROUND: The aim of this study was to obtain consensus amongst consultant surgeons on the attributes of a good surgical trainer that can be used to inform continuing professional development programmes for trainers. METHODS: good trainer attributes were generated from an intensive qualitative study using a participative inquiry process with consultant general surgeons and specialist registrars in the Tayside region. These good trainer attributes were then used as the basis of a modified Delphi study; the early rounds of the Delphi simultaneously sought participants' views concerning stated attributes and sought to generate new attributes. A final Delphi questionnaire was sent to all 180 consultant general surgeons in Scotland to identify consensus. RESULTS: The first two rounds of the Delphi process produced 45 attributes covering seven themes: interest in training, trainer as a team member, communication, receptiveness to trainee needs, trainer as a role model, reflection on practice and clinical and operative competence. The final survey identified significant consensus among surgeons. Clinical and operative competence achieved the highest consensus with 89.2% of surgeons believing it to be an essential attribute. CONCLUSIONS: The results indicate that there is consensus on the seven themes identified as essential for a trainer in general surgery. The recognition of the importance by trainers of non-surgical trainer attributes in the changed training structure is encouraging. Surgeons' level of awareness of their roles as a trainer will help inform the level and direction of trainer training and support required as part of a flexible and continuing developmental process.

Education, Medical, Graduate↗

PubMed2003

The interrupted serosubmucosal anastomosis - still the gold standard.

BACKGROUND: The single-layer appositional serosubmucosal anastomosis is a well established technique and appears to have a favourable record. Over a 15-year period the senior author of this paper has performed or directly supervised 553 anastomoses using this technique. This report describes the results of these operations, the results of stapled anastomoses carried out during the same period and discusses the utility of the handsewn technique. METHODS: From August 1986 to July 2001, 553 intestinal anastomoses in 550 patients were fashioned using single-layer, interrupted serosubmucosal 3/0 braided polyamide and 131 anastomoses in 131 patients were performed using a circular anastomosing stapler. RESULTS: One anastomotic leakage occurred in the group of patients whose anastomosis was handsewn (0.2%) and 11 leaks occurred in those who had a stapled anastomoses (8.4%). The mortality rate in each group was similar (2% and 2.3%, respectively). There were no deaths attributable to anastomotic dehiscence in either group. CONCLUSION: In this prospectively audited series of 553 handsewn anastomoses the leakage rate was 0.2%. These results compare favourably with other published series and continue to support a single layer of interrupted serosubmucosal sutures as the gold standard for anastomoses involving the large or small bowel.

Anastomosis, Surgical↗

PubMed2002

The colorectal adenoma-carcinoma sequence.

BACKGROUND: It is widely accepted that the adenoma-carcinoma sequence represents the process by which most, if not all, colorectal cancers arise. The evidence supporting this hypothesis has increased rapidly in recent years and the purpose of this article is to review this evidence critically and highlight its clinical significance. METHODS: Medline searches were used to identify recent key articles relating to the adenoma-carcinoma sequence. Further pertinent articles were obtained by manual scanning of the reference lists of identified papers. RESULTS: The evidence supporting the adenoma-carcinoma sequence can be classified as epidemiological, clinicopathological and genetic. The most recent and largest body of data relates to molecular genetic events and their cellular effects; however, many other approaches, such as cytogenetics, molecular cytogenetics and cytometry, have also yielded valuable information. CONCLUSION: Recent work continues to support the adenoma-carcinoma sequence, but there is a paucity of data on the interrelationship between different genetic mutations and on the relationship between molecular and other types of genetic abnormalities. The clinical utility of the observations described has yet to be fully realized and global genetic analysis of colorectal tumours may prove to be central in rational adenoma management.

Adenoma↗

PubMed2002

Management of colorectal cancer.

Colorectal cancer is the second most common cause of cancer death in the UK. Prompt investigation of suspicious symptoms is important, but there is increasing evidence that screening for the disease can produce significant reductions in mortality. High quality surgery is of paramount importance in achieving good outcomes, particularly in rectal cancer, but adjuvant radiotherapy and chemotherapy have important parts to play. The treatment of advanced disease is still essentially palliative, although surgery for limited hepatic metastases may be curative in a small proportion of patients.

Chemotherapy, Adjuvant↗

PubMed2002

Colonoscopy.

Colonoscopy is now the gold standard method for investigating most colonic symptoms. However, it is a demanding procedure that can be associated with low completion rates and significant complications, and it requires considerable skill to perform colonoscopy consistently well and safely. In this article, the key steps in performing colonoscopy are described with a view to providing the trainee with a logical sequence of manoeuvres on which to base a sound technique.

Colonoscopes↗