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A J Munro

Publications and source records attributed to A J Munro.

At least 19 recordsLinked to original sources
PubMed2006

Smoking compromises cause-specific survival in patients with operable colorectal cancer.

AIMS: To assess whether active smoking compromises survival in patients with colorectal cancer. MATERIALS AND METHODS: We studied a regionally based cohort of 284 consecutive patients referred to the Tayside Cancer Centre for consideration of adjuvant treatment after curative surgery for colorectal cancer. RESULTS: Cause-specific survival was significantly worse (P = 0.0015) in patients who were actively smoking at the time of their first post-operative visit. The absolute difference in 5-year cause-specific survival (active smokers vs the rest) was 21%. In adjusted multi-variate analysis of patients after pathologically complete (R0) resection, the hazard ratio was 2.55 (95% confidence interval 1.40-4.64) in active smokers compared with non-smokers. T stage, number of positive nodes and co-morbidity score were also of independent prognostic influence. CONCLUSIONS: Persistent smoking was, in this small series, an important and independent predictor of cancer-related death after surgery for cancer of the large bowel. Because smoking and deprivation are related, some of the adverse effects of deprivation upon survival in this group of patients may be explained by smoking behaviour.

Chemotherapy, Adjuvant↗
PubMed2006

Particle matters.

Explore the source record for details and available documents.

Fast Neutrons↗
PubMed2005

P53 abnormalities and outcomes in colorectal cancer: a systematic review.

We performed a systematic review of studies that investigated the effect of abnormalities of the tumour suppressor gene p53 upon prognosis in patients with colorectal cancer. The methods used to assess p53 status were immunohistochemistry (IHC), indicating abnormal accumulation of p53, and sequence analysis, indicating presence of p53 mutations (mut). We identified 168 reports, with 241 comparisons of relevant end points and survival data on 18 766 patients. We found evidence of both publication bias and heterogeneity of results. Our analysis was hampered by variability in both the assessment of p53 status and the reporting of results. We used a trim and fill method to correct for publication bias and minimised heterogeneity by using well-defined clinical subgroups for the assessment of outcomes. Overall, patients with abnormal p53 were at increased risk of death: relative risk (RR) with IHC 1.32 (95% confidence interval (c.i.) 1.23-1.42) and with mutation analysis 1.31 (95% c.i. 1.19-1.45). The adverse impact of abnormal p53 was greater in patients with lower baseline risk of dying: good prognosis RR (mut) 1.63 (95% c.i. 1.40-1.90) and poor prognosis RR (mut) 1.04 (95% c.i. 0.91-1.19). We found no effect of abnormal p53 on outcome in patients treated with chemotherapy. Abnormal p53 was associated with failure of response to radiotherapy in patients with rectal cancer: RR (mut) 1.49 (95% c.i. 1.25-1.77).

Bias↗
PubMed2005

Chinese medical herbs for chemotherapy side effects in colorectal cancer patients.

BACKGROUND: Side effects, including nausea and vomiting, sore mouth , diarrhoea, hepatotoxicity, myelosuppression, and immunosuppression , are commonly encountered in patients with colorectal cancer who are treated with chemotherapy. A variety of Chinese herbal medicines have been used for managing these adverse effects. OBJECTIVES: To assess the effect of herbal medicines plus chemotherapy, compared with chemotherapy alone, on the side effects of chemotherapy on the quality of life, and on adverse events in patients with colorectal cancer. SEARCH STRATEGY: We searched the Cochrane Library, MEDLINE, EMBASE, CBM, and handsearched the relevant Chinese journals. SELECTION CRITERIA: Randomised trials comparing either chemotherapy only or chemotherapy plus anti-emetics (tropisetron, sulpiride etc) with chemotherapy plus Chinese herbs. DATA COLLECTION AND ANALYSIS: Trial quality was assessed independently by two reviewers. Data were extracted by one reviewer and checked by the second reviewer. Since the four included studies differed significantly in design, we could only perform limited meta-analyses. We have therefore presented the majority of the data in narrative form. MAIN RESULTS: We included four relevant trials. All of them were of low quality. All of studies used a decoction containing Huangqi compounds as the intervention with chemotherapy. The intervention groups of three studies were compared to a chemotherapy alone control group, the fourth study compared the decoction of Huangqi compounds with two other Chinese herbal interventions. None of the studies reported on primary outcome using Common Toxicity Criteria (CTC). There was a significant reduction in the proportion of patients who experienced nausea & vomiting when decoctions of Huangqi compounds were given in addition to chemotherapy. There was also a decrease in the rate of leucopenia (WBC <3 x 10(9) per L). Huangqi compounds were also associated with increases in the proportions of T-lymphocyte subsets: CD3; CD4 and CD8. Huangqi decoctions had no significant effects on Immunoglobulins G, A or M. AUTHORS' CONCLUSIONS: Despite the included studies being of low quality, the results suggest that decoctions of Huangqi compounds may stimulate immunocompetent cells and decrease side effects in patients treated with chemotherapy. Due to the methodological limitations of the studies, there is no robust demonstration of benefit. We found no evidence of harm arising from the use of Chinese herbs. We need high quality randomised controlled studies investigating the effects of decoctions of Chinese herbs, particularly Astragalus spp.(as in Huangqi), upon chemotherapy-related side effects.

Antineoplastic Agents↗
PubMed2004

Deprivation, comorbidity and survival in a cohort of patients with colorectal cancer.

We studied a regionally based cohort of 483 consecutive patients with colorectal cancer referred for chemotherapy and/or radiotherapy. These patients were assessed and managed according to consistent policies. We investigated the effects of socio-economic deprivation and comorbidity upon survival. Significant comorbidity was present in 48% of the patients. Overall survival and cause-specific survival were summarized using Kaplan-Meier curves. Equality of survivor functions was assessed using the logrank procedure and Cox's proportional hazards analysis. In univariate analysis, the following variables significantly affected survival: comorbidity, performance status, age and clinical stage. We could find no correlation between deprivation and comorbidity. The presence of comorbidity significantly affected cause-specific survival (3-year cause-specific survival without comorbidity 54.2%; with comorbidity 44.6%). In adjusted analysis, deprivation had an independently adverse effect on overall survival, hazard ratio 1.04 (95% confidence interval 1.00-1.08), but this was only of borderline statistical significance, P = 0.049. This study demonstrates that the interrelationships between comorbidity, deprivation and outcome in this group of patients are complex: even when care is readily available, patient assessments are uniform, and clinical decision making is consistent.

Adult↗
PubMed1999

Remifentanil in emergency caesarean section in pre-eclampsia complicated by thrombocytopenia and abnormal liver function.

We describe the use of remifentanil in a woman with severe pre-eclampsia who presented for emergency caesarean section. Remifentanil was effective in obtunding the hypertensive response to laryngoscopy and intubation. Previous studies have found no significant adverse effects of remifentanil on the neonate. With its short duration of action, the use of this new opioid has several potential advantages in the above setting. Further studies are required to explore the use of remifentanil as an adjunct to obstetric general anaesthesia.

Adult↗
PubMed1998

Nurse-administered subcutaneous morphine is a satisfactory alternative to intravenous patient-controlled analgesia morphine after cardiac surgery.

UNLABELLED: There are no comparisons of i.v. patient controlled analgesia (i.v. PCA) versus nurse-administered subcutaneous (NA s.c.) morphine for acute postoperative pain. We undertook a prospective, randomized, controlled clinical trial of 80 cardiac surgical patients to compare i.v. PCA with NA s.c. morphine for postoperative pain control. Visual analog scale (VAS) pain scores at rest and with movement, daily verbal pain relief scores, and side effect profiles were not significantly different. Total morphine requirements in the two groups were not significantly different. A physiotherapist's evaluation of the effectiveness of analgesia for chest physiotherapy revealed no difference between the two groups. We conclude that NA s.c. morphine, administered as required (up to hourly), is a satisfactory alternative to i.v. PCA morphine after cardiac surgery. IMPLICATIONS: In a prospective, randomized study, we have shown that nurse-administered subcutaneous morphine is a satisfactory alternative to i.v. patient-controlled analgesia after cardiac surgery.

Aged↗
PubMed1996

External beam and intraluminal radiotherapy for locally advanced bile duct cancer: role and tolerability.

BACKGROUND AND PURPOSE: Cholangiocarcinoma is rare but carries a poor prognosis. Radiotherapy has been used either as an adjuvant treatment following surgical resection of tumour or for palliation. The purpose of this study was to assess the feasibility and morbidity of accelerated external beam radiotherapy with or without intraluminal radiotherapy in the treatment of locally advanced bile duct cancer. MATERIALS AND METHODS: Thirty eight patients were treated. Surgical procedures performed prior to radiotherapy were extended hepatectomy (3), hepaticojejunostomy with tumour resection (6), palliative biliary-enteric bypass (6), biopsy (4), Whipple's procedure (1), gastrojejunostomy (1) and cholecystectomy (1). Twenty patients received external beam radiotherapy (ERT). Six patients received one Phase of ERT and 12 received two Phases, separated by a 2-week gap. Dose per Phase was 22.5 Gy in 10 twice daily fractions. After 1989, dose per Phase was increased to 27.5 Gy. One patient received Phase I ERT (30.0 Gy) using conventional fractionation and one patient received an uninterrupted, conventionally fractionate course of treatment (50.0 Gy). Fourteen patients received both ERT and intraluminal radiotherapy (IRT) using iridium-192 (192Ir) wire passed through a percutaneous, transhepatic catheter (median dose, ERT 23.8 Gy + IRT 40.0 Gy). In addition, four patients received IRT alone (median dose 45.0 Gy at 1 cm radius). Patients were followed for at least 42 months. RESULTS: Median overall survival was 15 months. Overall survival for the whole group at 1,2 and 3 years was 59.6%, 32.5% and 16.2%. Thirty four patients died of disease. Radiotherapy caused acute toxicity in seven patients. According to RTOG/EORTC criteria toxicity was Grade 1 in four cases, Grade 2 in two cases and Grade 3 in one case. Two patients developed gastrointestinal bleeding as a late complication of radiotherapy. CONCLUSIONS: Accelerated external beam radiotherapy with or without intraluminal radiotherapy is feasible and associated with acceptable toxicity when used in the management of advance cholangiocarcinoma.

Bile Duct Neoplasms↗
PubMed1996

Construction and characterisation of a recombinant vaccinia virus expressing human papillomavirus proteins for immunotherapy of cervical cancer.

The presence and consistent expression of the genes encoding the human papillomavirus (HPV) E6 and E7 proteins in the great majority of cervical tumours presents the opportunity for an immunotherapeutic approach for control of the disease. This report describes the construction and characterisation of a recombinant vaccinia virus designed to express modified forms of the E6 and E7 proteins from HPV16 and HPV18, the viruses most commonly associated with cervical cancer. The recombinant virus (designated TA-HPV) was based on the Wyeth vaccine strain of vaccinia, and was shown to express the desired gene products. Studies in mice indicated that the recombinant virus was less neurovirulent than the parental virus and was capable of inducing an HPV-specific CTL response. This pre-clinical evaluation has provided a basis for the initiation of human trials in cervical cancer patients.

Amino Acid Sequence↗
PubMed1996

A modelled comparison of the effects of using different ways to compensate for missed treatment days in radiotherapy.

There is much evidence for the detrimental effect on tumour control of missed treatment days during radiotherapy, amounting for example to approximately a 1.6% absolute decrease in local control probability per day of treatment prolongation in the case of head and neck squamous cell cancer. Various methods to compensate for missed treatment days are compared quantitatively in this article, using the linear-quadratic formalism. The overall time and fraction size can be maintained by either treating on weekend days (the preferred way (Method 1a), although with unsocial hours and at extra cost) or using two fractions per day to "catch up' (Method 1b). The latter might incur a small loss of tolerance regarding late reactions, when intervals of 6-8 h are used rather than 24 h, and there may be logistical/scheduling difficulties with larger numbers of patients in some centres when using this method. A second type of strategy retains overall treatment time, and also one fraction per day, but the size of the dose per fraction is increased. For example, this may be done for the same number of "post-gap' days as gap days (Method 2). However, with this method, calculated isoeffect doses regarding late reactions indicate a probable decrease in tumour control rate (Method 2a). Otherwise, isoeffective doses regarding tumour control result in an increase in late reactions (Method 2b). In addition, this method is unsuitable for short regimens already using high doses per fraction. To reduce this problem, overall treatment time can also be retained by using fewer fractions, all of greater size in the case of planned gaps (statutory holidays), or larger remaining fractions after unplanned gaps (Method 2c). The problem also with this method is that equivalence for tumour control gives an increase in late reactions. The least satisfactory strategy (Method 3) is to accept the protraction caused by the missed treatment days, and give either the same prescribed number of (slightly larger) fractions or the planned treatment followed by one (or more) extra fraction to compensate for the gap. This would retain the expected local control rate, but there would be an increase in late reactions. An example of this, using average parameter values, is that a 3-day gap (necessitating four extra days to complete treatment with one fraction of 2.4 Gy) might maintain a 70% local control rate for glottic carcinoma, but severe reactions might rise from 1% to 4% and minor/moderate reactions from 37% to 50%. In this example, the inclusion of an extra weekend would increase the required extra dose and hence may further increase the morbidity rates. A final point is that the effect of treatment interruptions for an individual patient is expected to be greater than that for a group of patients because of interpatient heterogeneity tending to flatten dose-response curves. Calculations show that the above value of 1.6% loss of local control per day for a group of patients may reflect values for individual patients that range around a median value of as much as 5% per day, so stressing further the importance of gaps in treatment. It is concluded that, wherever possible, treatment days should not be missed. If they are missed, it is important to compensate for them, preferably by one of the first of the above methods (1a or 1b), in order to keep as close as possible to the original/standard prescription in terms of total dose, dose per fraction and overall time.

Brachytherapy↗
PubMed1996

A quantitative approach to the distress caused by symptoms in patients treated with radical radiotherapy.

A computerised self-assessment instrument was used to capture data on the distress caused by symptoms in 110 patients treated with radical radiotherapy. Patients selected symptoms from a list of 34 problems and then quantified the distress associated with each problem using a linear Analogue self assessment (LASA)-type scale. The test instrument was feasible: 90% of assessments were completed in under 14 min. There was a significant increase in tiredness and significant decrease in anxiety and worries about the family, during treatment. Menopausal symptoms and post-surgical problems were important causes of distress in the patients with breast cancer. When the area under the curve method was used to quantify distress in the patients with breast cancer, difficulty concentrating, pain and sleep disturbances emerged as significantly troublesome problems. Computerised self-assessment may have a useful role in quantifying the distress caused by treatment with radiotherapy.

Adult↗
PubMed1996

Anti-CD45 and anti-CD52 (Campath) monoclonal antibodies effectively eliminate systematically disseminated human non-Hodgkin's lymphoma B cells in Scid mice.

Severe combined immunodeficient (Scid) mice inoculated with the human (t(14;18)-positive B cell lines DoHH2 and BEVA develop lethal systemically disseminated lymphoma (de Kroon et al., Leukemia 8:1385, and Blood 80 [suppl 1]:436). These models were used to study the therapeutic effect of rat-anti-human CD52 (Campath-1G) or CD45 monoclonal antibodies (mAbs) on systemically disseminated tumor cells and on tumor cells present in solid tumor masses. Both mAbs were effective in inhibiting growth of systemically disseminated malignant cells. When treatment with anti-CD52 or anti-CD45 mAbs at a dose of 30 micrograms/mouse/d for 4 days was started 24 hours after intravenous inoculation of human DoHH2 or BEVA cells, a 3-log kill of tumor cells was observed as measured by prolonged survival. After treatment, surviving animals injected with high numbers of BEVA cells showed tumor masses in liver, kidney, and mesenteric lymph nodes. In contrast to nontreated animals, however, only low numbers of malignant cells were found in peripheral blood, and bone marrow was free of tumor cells. Similarly, after mAb treatment of mice inoculated subcutaneously (sc) with DoHH2 cells, no tumor cells could be found in the bone marrow, and few DoHH2 cells could be detected in the peripheral blood, spleen, liver, kidney, or lung. In contrast, tumor cells present in subcutaneous tumors and axillary lymph nodes were relatively unaffected by mAb therapy. The presence of rat immunoglobulin (Ig) could be demonstrated on surviving tumor cells. The presence of murine macrophages in areas in these tumors that were depleted of DoHH2 cells suggested that the mAb-mediated antitumor effect observed in the Scid mouse model is mediated by cellular mechanisms. Apparently these mechanisms were not sufficient to eliminate the fast-growing tumor cells present in the protected sites. Our results indicate that treatment with anti-CD52 or anti-CD45 mAbs potentially may be useful as adjuvant immunotherapy for systemically disseminated B cell lymphoma.

Animals↗