Surgery (Austin & Northern Health) - Research Publications
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ItemCapecitabine and mitomycin C as third-line therapy for patients with metastatic colorectal cancer resistant to fluorouracil and irinotecan.(Springer Science and Business Media LLC, 2005-09-05)Protracted venous infusion 5-fluorouracil (5FU) combined with mitomycin C (MMC) has demonstrated significant activity against metastatic colorectal cancer. Owing to potential synergy based upon upregulation of thymidine phosphorylase by MMC, the combination of capecitabine and MMC may improve outcomes in irinotecan-refractory disease. Eligible patients with progressive disease during or within 6 months of second-line chemotherapy were treated with capecitabine (1250 mg m(-2) twice daily) days 1-14 every 3 weeks and MMC (7 mg m(-2) IV bolus) once every 6 weeks. A total of 36 patients were recruited, with a median age of 64 years (range 40-77), and 23 patients (78%) were performance status 0-1. The objective response rate was 15.2%. In all, 48.5% of patients had stable disease. Median failure-free survival was 5.4 months (95% CI 4.6-6.2). Median overall survival was 9.3 months (95% CI: 6.9-11.7). Grade 3 toxicities were palmar-plantar erythema 16.7%, vomiting 8.3%, diarrhoea 2.8%, anaemia 8.3%, and neutropenia 2.8%. No patients developed haemolytic uraemic syndrome. Symptomatic improvement occurred for pain, bowel symptoms, and dyspnoea. Capecitabine in combination with MMC is an effective regimen for metastatic colorectal cancer resistant to 5FU and irinotecan with an acceptable toxicity profile and a convenient administration schedule.
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ItemPhase II study of capecitabine and mitomycin C as first-line treatment in patients with advanced colorectal cancer.(Springer Science and Business Media LLC, 2004-08-31)This study was designed to assess the safety and efficacy of capecitabine and mitomycin C (MMC) in previously untreated patients with advanced colorectal cancer (CRC). Patients received capecitabine 2500 mg m(2) day 1, orally divided in two doses of 1250 mg m(-2) in the morning and evening for 14 days every 21 days and MMC 7 mg m(-2) (maximum total dose 14 mg) as an intravenous bolus every 6 weeks for a total of four courses. The median age was 70 years (range 24-85) and the majority of patients (86.9%) were of performance status 1/2. The most common metastatic site was liver. In all, 84 patients were assessable for response. The overall response rate was 38% (95% CI: 27.7-49.3) and a further 33.3% of patients achieved stable disease over 12 weeks. There was good symptom resolution ranging from 64 to 86%. Grade 3/4 toxicity was as follows: hand-foot syndrome 19.7%; diarrhoea 10%; neutropenia 2.4%; infection 2.3%. Capecitabine and MMC have shown encouraging activity with a favourable toxicity profile, a convenient administration schedule, and could be considered for patients deemed unsuitable for oxaliplatin and irinotecan combinations.
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ItemAnalysis of the time course and prognostic factors determining toxicity due to infused fluorouracil.(Springer Science and Business Media LLC, 2003-05-19)This study used a prospectively managed clinical database in order to identify 1470 patients with gastrointestinal cancers receiving protracted venous infusion (PVI) fluorouracil (5FU). It aimed to determine the time course of toxicity due to PVI 5FU and to analyse factors predicting toxicity. The initial development of stomatitis occurred more rapidly than diarrhoea or palmar plantar erythema (PPE). The percentage of patients with National Cancer Institute Common Toxicity Criteria (CTC) grade 2 or worse PPE peaked at 9% between weeks 8 and 17, whereas this peak occurred earlier for stomatitis and diarrhoea. The development of CTC grade 1 toxicity in the first 28 days after commencement of chemotherapy was classified as early grade 1 toxicity. Multivariate Cox regression analysis showed that female sex, better performance status, elevated bilirubin, early grade 1 PPE and early grade 1 diarrhoea were independent prognostic factors for the development of CTC grade 2 or worse PPE (P<0.01). Female sex, increased age, elevated alanine transaminase and urea and early grade 1 PPE were significant independent prognostic factors for the development of CTC grade 2 or worse stomatitis (P<0.01). Early CTC grade 1 diarrhoea predicted CTC grade 2 or worse diarrhoea (P<0.01). Older, female patients with good performance status and impaired liver and renal function who develop early grade 1 PPE alone or in combination with diarrhoea are at highest risk of subsequently developing grade 2 or worse PPE or stomatitis during treatment with PVI 5FU. Reduction of infused 5FU dose should be considered for these patients. Such an approach could both reduce severe toxicity owing to chemotherapy and minimise treatment delays, and should be evaluated prospectively.
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ItemReport of two protocol planned interim analyses in a randomised multicentre phase III study comparing capecitabine with fluorouracil and oxaliplatin with cisplatin in patients with advanced oesophagogastric cancer receiving ECF.(Springer Science and Business Media LLC, 2005-06-06)The purpose of the study was to establish the optimal dose of capecitabine (X) to be used within a multicentre, randomised study evaluating the potential roles of oxaliplatin (O) and X in chemonaive patients (pts) with advanced oesophagogastric cancer. Two by two design was used, and pts were randomised to one of four regimens and stratified for extent of disease, performance status (PS) and centre. The treatment regimens are epirubicin, cisplatin, 5-fluorouracil (ECF), EOF, ECX or EOX. Doses: E 50 mg m(-2), C 60 mg m(-2) and O 130 mg m(-2) i.v. 3 weekly; F 200 mg m(-2) day(-1) i.v. and X 500 mg m(-2) b.i.d.(-1) (escalated to 625 mg m(-2) b.i.d.(-1) after results of first interim analysis) p.o., continuously. First interim analysis was performed when 80 pts had been randomised. Dose-limiting fluoropyrimidine toxicities were stomatitis, palmar plantar erythema (PPE) and diarrhoea; 5.1% of X-treated pts experienced grade 3/4 toxicity. Protocol planned dose escalation of X to 625 mg m(-2) b.i.d.(-1) was instituted and a second interim analysis has been performed; results are presented in this paper. A total of 204 pts were randomised at the time of the protocol planned 2nd interim analysis. Grade 3/4 fluoropyrimidine-related toxicity was seen in 13.7% pts receiving F, 8.4% pts receiving X 500 mg m(-2) b.i.d.(-1) and 14.7% pts receiving X 625 mg m(-2) b.i.d.(-1). Combined complete and partial response rates were ECF 31% (95% CI 18.7-46.3), EOF 39% (95% CI 25.9-53.1), ECX 35% (95% CI 21.4-50.3), EOX 48% (95% CI 33.3-62.8). Grade 3/4 fluoropyrimidine toxicity affected 14.7% of pts treated with X 625 mg m(-2) b.i.d.(-1), which is similar to that observed with F, confirming this to be the optimal dose. The replacement of C by O and F by X does not appear to impair efficacy. The trial continues to total accrual of 1000 pts.
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ItemSuccessful surgical treatment of a giant coronary artery aneurysm presenting with recurrent profuse haemoptysis.(Springer Science and Business Media LLC, 2008-06-29)We present the case of successful resection of a giant aneurysm of the LAD presenting with recurrent severe haemoptysis in a 72-year old man. He was admitted to a regional hospital with fever, recurrent bloody sputum, weight loss and left sided chest pain, and developed respiratory failure requiring ventilation. Investigations are summarised and reviewed and the diagnosis was eventually reached by TTE, CT and MRI scans, confirmed by coronary angiography. Successful emergency surgery to resect the aneurysm and put a vein graft to the LAD is described. The presentation and management of coronary giant aneurysm is reviewed.
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ItemAcute liver failure due to primary angiosarcoma: a case report and review of literature.(Springer Science and Business Media LLC, 2008-09-30)BACKGROUND: Hepatic angiosarcoma is a primary sarcoma of the liver, accounting for only 2% of all primary hepatic malignancies. Acute liver failure is an extremely rare presentation of a primary liver tumour. CASE PRESENTATION: We report a case of a seventy year-old man who presented with a very short period of jaundice leading to fulminant hepatic failure (FHF). On further investigation he was found to have primary angiosarcoma of liver. CONCLUSION: The treatment outcomes for hepatic angiosarcoma are poor, we discuss the options available and the need for prompt investigation and establishment of a diagnosis.
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ItemNurses' perceptions and experiences of communication in the operating theatre: a focus group interview.(Springer Science and Business Media LLC, 2006-02-08)UNLABELLED: Nurses' perceptions and experiences of communication in the operating theatre: a focus group interview BACKGROUND: Communication programmes are well established in nurse education. The focus of programmes is most often on communicating with patients with less attention paid to inter-professional communication or skills essential for working in specialised settings. Although there are many anecdotal reports of communication within the operating theatre, there are few empirical studies. This paper explores communication behaviours for effective practice in the operating theatre as perceived by nurses and serves as a basis for developing training. METHODS: A focus group interview was conducted with seven experienced theatre nurses from a large London teaching hospital. The interview explored their perceptions of the key as well as unique features of effective communication skills in the operating theatre. Data was transcribed and thematically analysed until agreement was achieved by the two authors. RESULTS: There was largely consensus on the skills deemed necessary for effective practice including listening, clarity of speech and being polite. Significant influences on the nature of communication included conflict in role perception and organisational issues. Nurses were often expected to work outside of their role which either directly or indirectly created barriers for effective communication. Perceptions of a lack of collaborative team effort also influenced communication. CONCLUSION: Although fundamental communication skills were identified for effective practice in the operating theatre, there were significant barriers to their use because of confusion over clarity of roles (especially nurses' roles) and the implications for teamwork. Nurses were dissatisfied with several aspects of communication. Future studies should explore the breadth and depth of this dissatisfaction in other operating theatres, its impact on morale and importantly on patient safety. Interprofessional communication training for operating theatre staff based in part on the key issues identified in this study may help to create clarity in roles and focus attention on effective teamwork and promote clinical safety.
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ItemNo Preview Available8th international conference: primary therapy of early breast cancer, St Gallen, Switzerland, March 12-15 2003.(Springer Science and Business Media LLC, 2003)The International St Gallen Breast Cancer Conference concentrates almost exclusively on adjuvant, multimodal primary therapy for early breast cancer. Begun 25 years ago, this meeting was initially held every 4 years, but therapeutic progress, new strategies and provocative trials data have accelerated to the extent that conferences are now held biennially. The meeting this year was attended by almost 3000 delegates. Major topics included new prognostic and predictive markers in early breast cancer, the best use of adjuvant chemotherapy and endocrine therapy, and innovations in local surgery and radiation therapy.
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ItemNo Preview AvailableIs reducing variability of blood glucose the real but hidden target of intensive insulin therapy?(BMC, 2009)Since the first report that intensive insulin therapy reduced mortality in selected surgical critically ill patients, lowering of blood glucose levels has been recommended as a means of improving patient outcomes. In this initial Leuven trial, blood glucose control by protocol using insulin was applied to 98.7% of patients in the intensive group but to only 39.2% (P < 0.0001) of patients in the control group. If appropriately applied, such protocols should decrease both the mean blood glucose concentration and its variability (variation of blood glucose concentration). Thus, it is logically possible that the benefit of intensive insulin therapy in the first Leuven trial was due to a decrease in mean glucose levels, a decrease in their variability, or both. Several recent studies have confirmed significant associations between variability of blood glucose levels and patient outcomes. Decreasing the variability of blood glucose levels might be an important dimension of glucose management, a possible mechanism by which an intensive insulin protocol exerts its putative beneficial effects, and an important goal of glucose management in the intensive care unit. Clinicians need to be aware of this controversy when considering the application of intensive insulin therapy and interpreting future trials.
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ItemNo Preview AvailableEffectiveness of the Medical Emergency Team: the importance of dose(BMC, 2009)Up to 17% of hospital admissions are complicated by serious adverse events unrelated to the patients presenting medical condition. Rapid Response Teams (RRTs) review patients during early phase of deterioration to reduce patient morbidity and mortality. However, reports of the efficacy of these teams are varied. The aims of this article were to explore the concept of RRT dose, to assess whether RRT dose improves patient outcomes, and to assess whether there is evidence that inclusion of a physician in the team impacts on the effectiveness of the team. A review of available literature suggested that the method of reporting RRT utilization rate, (RRT dose) is calls per 1,000 admissions. Hospitals with mature RRTs that report improved patient outcome following RRT introduction have a RRT dose between 25.8 and 56.4 calls per 1,000 admissions. Four studies report an association between increasing RRT dose and reduced in-hospital cardiac arrest rates. Another reported that increasing RRT dose reduced in-hospital mortality for surgical but not medical patients. The MERIT study investigators reported a negative relationship between MET-like activity and the incidence of serious adverse events. Fourteen studies reported improved patient outcome in association with the introduction of a RRT, and 13/14 involved a Physician-led MET. These findings suggest that if the RRT is the major method for reviewing serious adverse events, the dose of RRT activation must be sufficient for the frequency and severity of the problem it is intended to treat. If the RRT dose is too low then it is unlikely to improve patient outcomes. Increasing RRT dose appears to be associated with reduction in cardiac arrests. The majority of studies reporting improved patient outcome in association with the introduction of an RRT involve a MET, suggesting that inclusion of a physician in the team is an important determinant of its effectiveness.