Surgery (Western Health) - Research Publications
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ItemRisk factors for unfavourable postoperative outcome in patients with Crohn's disease undergoing right hemicolectomy or ileocaecal resection An international audit by ESCP and S-ECCO.(Wiley, 2017-09-15)BACKGROUND: Patient and disease-related factors, as well as operation technique all have the potential to impact on postoperative outcome in Crohn's disease. The available evidence is based on small series and often displays conflicting results. AIM: To investigate the effect of pre- and intra-operative risk factors on 30-day postoperative outcome in patients undergoing surgery for Crohn's disease. METHOD: International prospective snapshot audit including consecutive patients undergoing right hemicolectomy or ileocaecal resection. This study analysed a subset of patients who underwent surgery for Crohn's disease. The primary outcome measure was the overall Clavien-Dindo postoperative complication rate. The key secondary outcomes were anastomotic leak, re-operation, surgical site infection and length of stay at hospital. Multivariable binary logistic regression analyses were used to produce odds ratios (OR) and 95% confidence intervals (CI). RESULTS: Three hundred and seventy five resections in 375 patients were included. The median age was 37 and 57.1% were female. In multivariate analyses, postoperative complications were associated with preoperative parenteral nutrition (OR 2.36 95% CI 1.10-4.97)], urgent/expedited surgical intervention (OR 2.00, 95% CI 1.13-3.55) and unplanned intraoperative adverse events (OR 2.30, 95% CI 1.20-4.45). The postoperative length of stay in hospital was prolonged in patients who received preoperative parenteral nutrition (OR 31, CI [1.08-1.61]) and those who had urgent/expedited operations (OR 1.21, CI [1.07-1.37]). CONCLUSION: Preoperative parenteral nutritional support, urgent/expedited operation and unplanned intraoperative adverse events were associated with unfavourable postoperative outcome. Enhanced preoperative optimization and improved planning of operation pathways and timings may improve outcomes for patients. This article is protected by copyright. All rights reserved.
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ItemEmergency appendicectomy in Australia: findings from a multicentre, prospective study(WILEY, 2017-09)BACKGROUND: Emergency appendicectomy is the most common emergency surgical procedure performed in Australia. Despite this frequency, there is a relative paucity of contemporary, broad-based, local data that examine how emergency appendicectomies are currently performed and what are the outcomes from these operations. METHODS: A multicentre, prospective, observational study was performed. Patients were recruited by local investigators for a period of 2 months with 30-day follow-up. Patients were eligible for study inclusion if they underwent an emergency appendicectomy for suspected acute appendicitis. The primary outcome of the study was the negative appendicectomy rate (NAR), with secondary outcomes including 30-day complication rates, method of operation and conversion rates. RESULTS: A total of 1189 patients were recruited across 27 centres. The NAR across all centres was 19.0%. 98.2% of appendicectomies were performed with a laparoscopic-first approach. The rate of conversion from laparoscopy to open operation was 2.4%. 9.4% of patients were recorded as having one or more of the following complications: readmission (6.6%), surgical site infection (1.9%), intra-abdominal abscess (2.7%) or further intervention (1.5%). Patients who had an open operation had higher rates of readmission and surgical site infection. CONCLUSION: The NAR found in this study is within the traditional measures of acceptance; however, this rate is high when measured against modern international benchmarks.
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ItemExamining the impact of regular aspirin use and PIK3CA mutations on survival in stage 2 colon cancer(WILEY, 2017-01)BACKGROUND/AIM: Data suggest aspirin improves survival in colorectal cancer (CRC) harbouring PIK3CA mutations. The impact of aspirin is thought predominantly to be through an anti-inflammatory effect. The aim of this study is to explore the effect of aspirin use on survival in a real-world cohort of stage 2 colon cancer (CC) patients. METHODS: A prospective CRC database identified patients diagnosed with stage 2 CC between 2000 and 2011. PIK3CA mutation status was determined by next generation sequencing. Neutrophil-lymphocyte ratio greater than 5 at diagnosis represented systemic inflammation. Chart review was used to record regular aspirin use at diagnosis. Clinico-pathological features and survival data were available. Survival analyses used the Cox proportional hazards method. RESULTS: Of 488 patients with stage 2 CC, 95 patients were aspirin users and 70 patients had PIK3CA mutations. Aspirin users were more likely to be older (median: 76.4 years vs 68.3 years, P < 0.001), to be less fit (American Society of Anaesthetists Score 3-4: 58% vs 31%, P < 0.001) and to have systemic inflammation (neutrophil-lymphocyte ratio > 5: 39% vs 27%, P = 0.027). Regular aspirin use did not significantly improve recurrence-free survival. In the PIK3CA mutated group, there was a trend towards improved recurrence-free survival (hazard ratio: 0.45, P = 0.42). CONCLUSIONS: Our study did not demonstrate a significant survival advantage from aspirin use in stage 2 PIK3CA mutated CC. The 'real-world' nature of our cohort and the subsequent uncontrolled differences in age and fitness in aspirin users are likely to have contributed to this result. Defining the true impact of aspirin in CRC requires prospective randomised clinical trials.
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ItemLaparoscopic or open appendicectomy for suspected appendicitis in pregnancy and evaluation of foetal outcome in Australia(WILEY, 2017-05)BACKGROUND: Recent data suggest that laparoscopic appendicectomy (LA) in pregnancy is associated with higher rates of foetal loss when compared to open appendicectomy (OA). However, the influence of gestational age and maternal age, both recognized risk factors for foetal loss, was not assessed. METHOD: This was a multicentre retrospective review of all pregnant patients who underwent appendicectomy for suspected appendicitis from 2000 to 2012 across seven hospitals in Australia. Perioperative data and foetal outcome were evaluated. RESULTS: Data on 218 patients from the seven hospitals were included in the analysis. A total of 125 underwent LA and 93 OA. There were seven (5.6%) foetal losses in the LA group, six of which occurred in the first trimester, and none in the OA group. After matching using propensity scores, the estimated risk difference was 5.1% (95% confidence interval (CI): 1.4%, 9.8%). First trimester patients were more likely to undergo LA (84%), while those in the third were more likely to undergo OA (85%). Preterm delivery rates (6.8% LA versus 8.6% OA; CI: -12.6%, 5.3%) and hospital length of stay (3.7 days LA versus 4.5 days OA; CI: -1.3, 0.2 days) were similar. CONCLUSION: This is the largest published dataset investigating the outcome after LA versus OA while adjusting for gestational and maternal age. OA appears to be a safer approach for pregnant patients with suspected appendicitis.
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ItemManagement of Early Node-Positive Breast Cancer in Australia: A Multicentre Study(WILEY, 2016-07)To examine practice patterns for breast cancer patients with limited sentinel node (SN) disease in light of the ACOSOG Z0011 results. Retrospective analysis of patients with T1-2 breast cancer and positive sentinel lymph node biopsy (SLNB) admitted between January 2009 and December 2012. Patient demographics, tumor characteristics, and treatments were recorded. Eight hundred positive SLNBs were identified. A total of 452 (56.5%) proceeded to completion axillary lymph node dissection (cALND). cALND rate decreased from 65.1% to 49.7% from 2009-2010 to 2011-2012. cALND was performed for micrometastasis or isolated tumor cells in 39.3% in 2009-2010 and 22.2% in 2011-2012, whereas for macrometastases the rates were 83.1% and 68.6%, respectively. cALND rates diminished for both Z0011-eligible and -ineligible patients. The ACOSOG Z0011 trial presentation and publication coincided with a reduction in cALND for breast cancer with limited nodal disease. There appears equipoise regarding management of macrometastatic SN disease.
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ItemDifferent APC genotypes in proximal and distal sporadic colorectal cancers suggest distinct WNT/β-catenin signalling thresholds for tumourigenesis(NATURE PUBLISHING GROUP, 2013-09-26)Biallelic protein-truncating mutations in the adenomatous polyposis coli (APC) gene are prevalent in sporadic colorectal cancer (CRC). Mutations may not be fully inactivating, instead producing WNT/β-catenin signalling levels 'just-right' for tumourigenesis. However, the spectrum of optimal APC genotypes accounting for both hits, and the influence of clinicopathological features on genotype selection remain undefined. We analysed 630 sporadic CRCs for APC mutations and loss of heterozygosity (LOH) using sequencing and single-nucleotide polymorphism microarrays, respectively. Truncating APC mutations and/or LOH were detected in 75% of CRCs. Most truncating mutations occurred within a mutation cluster region (MCR; codons 1282-1581) leaving 1-3 intact 20 amino-acid repeats (20AARs) and abolishing all Ser-Ala-Met-Pro (SAMP) repeats. Cancers commonly had one MCR mutation plus either LOH or another mutation 5' to the MCR. LOH was associated with mutations leaving 1 intact 20AAR. MCR mutations leaving 1 vs 2-3 intact 20AARs were associated with 5' mutations disrupting or leaving intact the armadillo-repeat domain, respectively. Cancers with three hits had an over-representation of mutations upstream of codon 184, in the alternatively spliced region of exon 9, and 3' to the MCR. Microsatellite unstable cancers showed hyper-mutation at MCR mono- and di-nucleotide repeats, leaving 2-3 intact 20AARs. Proximal and distal cancers exhibited different preferred APC genotypes, leaving a total of 2 or 3 and 0 to 2 intact 20AARs, respectively. In conclusion, APC genotypes in sporadic CRCs demonstrate 'fine-tuned' interdependence of hits by type and location, consistent with selection for particular residual levels of WNT/β-catenin signalling, with different 'optimal' thresholds for proximal and distal cancers.
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ItemImpact of Diabetes Status and Medication on Presentation, Treatment, and Outcome of Stage II Colon Cancer Patients(HINDAWI LTD, 2015)Diabetes is a risk factor for colorectal cancer and several reports suggest worse cancer-specific outcomes in diabetes patients. Recent studies in multiple tumour types indicate metformin may positively impact on cancer-specific and overall survival. A population-based series of stage II colorectal cancer patients treated and followed from 2000 to 2013 were analysed for baseline characteristics, treatment, and outcomes. 1116 patients with stage II colon cancer were identified, 55.5% were male and median age was 70.9 years (range 20.5-101.2). The diabetes patients (21.6%, n = 241) were older than nondiabetes patients (median 74.0 versus 69.6, p = 0.0001). There was no impact of diabetes on cancer presentation or pathology. Diabetes patients were less likely to receive adjuvant treatment (13.7 versus 24.8%, p = 0.002) but were equally likely to complete treatment (69.7 versus 67.7%, p = 1.00). Diabetes did not significantly impact cancer recurrence (HR = 1.07, 95% CI 0.71-1.63) or overall survival (HR = 1.23, 95% CI 0.88-1.72), adjusted for age. Diabetes medication did not impact cancer recurrence or survival. Cancer presentation and outcomes in diabetes patients are comparable to those of nondiabetes patients in those with stage II colon cancer. The effect of metformin merits further evaluation in patients with colon cancer.
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ItemWild-type APC predicts poor prognosis in microsatellite-stable proximal colon cancer(NATURE PUBLISHING GROUP, 2015-09-15)BACKGROUND: APC mutations (APC-mt) occur in ∼70% of colorectal cancers (CRCs), but their relationship to prognosis is unclear. METHODS: APC prognostic value was evaluated in 746 stage I-IV CRC patients, stratifying for tumour location and microsatellite instability (MSI). Microarrays were used to identify a gene signature that could classify APC mutation status, and classifier ability to predict prognosis was examined in an independent cohort. RESULTS: Wild-type APC microsatellite stable (APC-wt/MSS) tumours from the proximal colon showed poorer overall and recurrence-free survival (OS, RFS) than APC-mt/MSS proximal, APC-wt/MSS distal and APC-mt/MSS distal tumours (OS HR⩾1.79, P⩽0.015; RFS HR⩾1.88, P⩽0.026). APC was a stronger prognostic indicator than BRAF, KRAS, PIK3CA, TP53, CpG island methylator phenotype or chromosomal instability status (P⩽0.036). Microarray analysis similarly revealed poorer survival in MSS proximal cancers with an APC-wt-like signature (P=0.019). APC status did not affect outcomes in MSI tumours. In a validation on 206 patients with proximal colon cancer, APC-wt-like signature MSS cases showed poorer survival than APC-mt-like signature MSS or MSI cases (OS HR⩾2.50, P⩽0.010; RFS HR⩾2.14, P⩽0.025). Poor prognosis APC-wt/MSS proximal tumours exhibited features of the sessile serrated neoplasia pathway (P⩽0.016). CONCLUSIONS: APC-wt status is a marker of poor prognosis in MSS proximal colon cancer.
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ItemIs the routine use of a water-soluble contrast enema prior to closure of a loop ileostomy necessary? A review of a single institution experience.(Springer Science and Business Media LLC, 2015-12-04)BACKGROUND: The aims of the study were to determine the radiological leak rate in those patients who had undergone a resection for left-sided colorectal cancer and to see if the presence of a leak can be related with the postoperative clinical period. We also aimed to identify any common factors between patients with leak. METHODS: A retrospective analysis of prospectively collected data of all patients who underwent a left-sided colorectal cancer resection with formation of a defunctioning ileostomy was undertaken. Between 2005 and 2010, 418 such patients were identified. RESULTS: A water-soluble contrast enema was performed in 339 patients (81.1 %). Of these, 24 (7.1 %) were reported to show an anastomotic leak. Data for these 24 patients is presented in this study. Twenty-three (95.8 %) of the leaks occurred in patients who had undergone an anterior resection; 95.8 % of the patients with a leak were male. Fifteen (62.5 %) patients underwent neo-adjuvant radiation. The mean length of stay in those patients shown to have a subsequent radiological leak was 18.8 days (median), compared with the overall unit figures of 12 days. Only 29.2 % of the patients who had a leak identified had an uncomplicated postoperative period. Overall 87.5 % of the patients had a reversal of the ileostomy. CONCLUSIONS: Radiological leakage is not uncommon. The majority of patients, who were shown to have a radiological leak in this study, were male, had undergone an anterior resection, had received neo-adjuvant radiation, had a longer initial length of stay and had postoperative complications. Water-soluble contrast enemas could be selectively used in patients with these characteristics.