- Professor Merrett is the Foundation Professor of Surgery for Western Sydney University. He has an extensive research ... moreProfessor Merrett is the Foundation Professor of Surgery for Western Sydney University. He has an extensive research profile in pancreatic and oesophageal cancer treatments, patterns of care, disease burden on health system and clinicopathological outcomes with over 1500 citations of his 84 publications and a H index of 18. He has been facilitated and encouraged collaborative research by his junior staff and was a driver for the collaborative research within SWS to the APCGI project at the Garvan Institute.
He has extensive experience in planning and implementation of clinical services in SWSLHD and the State. Amongst these are
• Within SWSLHD: He is on LHD Board; Is Chair of the Board Healthcare Quality and Safety Committee; is Head of Upper GI surgery for SWSLHD; is SWSLHD Director of Surgery; is Director of Surgery for Campbelltown Hospital;. is the coordinator for the SWSLHD Low volume Oncology service. He has been an author of numerous planning document from “Way Forward” planning document for SSWAHS to the current Strategic Directions to 2021 Document for SWSLHD. He was Clinical Stream Director of Gastroenterology and Liver Services from 2004 to 2012.
• State Level: He is a member of the NSW State Surgical Taskforce and The Paediatric General Surgical Workforce Committee (within ACI); Is a member of The Surgical Optimisation Working group, the Upper GI NSWOG Committee, and Chairs the Protocols and Policies Working Party, for Oesophagogastric and Pancreatic Cancer (within the NSW Cancer Institute). He also sits on the Governing Council of the State Scope of Clinical Practice Unit
• Nationally: He sits on the Board of ANZGOSA, the Training Committee of ANZGOSA and the Executive Committee of the Upper GI Section of RACS
Professor Merrett has made significant contributions to education and training both undergraduates and postgraduates Within Western Sydney University, he Heads the Discipline of Surgery, he revised the Surgical Curriculum, is the Year 5 Programme Coordinator, and participates in the full Conference week programme and exams. He is the Supervisor of Training for both the ANZGOSA and ANZHPBA Fellows within SWSLHDedit
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IntroductionSurvival from oesophageal cancer remains poor, even across high-income countries. Ongoing changes in the epidemiology of the disease highlight the need for survival assessments by its two main histological subtypes,... more
IntroductionSurvival from oesophageal cancer remains poor, even across high-income countries. Ongoing changes in the epidemiology of the disease highlight the need for survival assessments by its two main histological subtypes, adenocarcinoma (AC) and squamous cell carcinoma (SCC).MethodsThe ICBP SURVMARK-2 project, a platform for international comparisons of cancer survival, collected cases of oesophageal cancer diagnosed 1995 to 2014, followed until 31st December 2015, from cancer registries covering seven participating countries with similar access to healthcare (Australia, Canada, Denmark, Ireland, New Zealand, Norway and the UK). 1-year and 3-year age-standardised net survival alongside incidence rates were calculated by country, subtype, sex, age group and period of diagnosis.Results111 894 cases of AC and 73 408 cases of SCC were included in the analysis. Marked improvements in survival were observed over the 20-year period in each country, particularly for AC, younger age gr...
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We aimed to define preoperative clinical and molecular characteristics that would allow better patient selection for operative resection. Although we use molecular selection methods for systemic targeted therapies, these principles are... more
We aimed to define preoperative clinical and molecular characteristics that would allow better patient selection for operative resection. Although we use molecular selection methods for systemic targeted therapies, these principles are not applied to surgical oncology. Improving patient selection is of vital importance for the operative treatment of pancreatic cancer (pancreatic ductal adenocarcinoma). Although surgery is the only chance of long-term survival, 80% still succumb to the disease and approximately 30% die within 1 year, often sooner than those that have unresected local disease. In 3 independent pancreatic ductal adenocarcinoma cohorts (total participants = 1184) the relationship between aberrant expression of prometastatic proteins S100A2 and S100A4 and survival was assessed. A preoperative nomogram based on clinical variables available before surgery and expression of these proteins was constructed and compared to traditional measures, and a postoperative nomogram. High expression of either S100A2 or S100A4 was independent poor prognostic factors in a training cohort of 518 participants. These results were validated in 2 independent patient cohorts (Glasgow, n = 198; Germany, n = 468). Aberrant biomarker expression stratified the cohorts into 3 distinct prognostic groups. A preoperative nomogram incorporating S100A2 and S100A4 expression predicted survival and nomograms derived using postoperative clinicopathological variables. Of those patients with a poor preoperative nomogram score, approximately 50% of patients died within a year of resection. Nomograms have the potential to improve selection for surgery and neoadjuvant therapy, avoiding surgery in aggressive disease, and justifying more extensive resections in biologically favorable disease.
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Symptomatic cholelithiasis accounts for a significant burden of emergency general surgical presentations in Australia and the Western population. Access to hepatobiliary ultrasonography to facilitate diagnosis can lead to delays in timely... more
Symptomatic cholelithiasis accounts for a significant burden of emergency general surgical presentations in Australia and the Western population. Access to hepatobiliary ultrasonography to facilitate diagnosis can lead to delays in timely treatment. Surgical ultrasonography at the bedside (SUB) can mitigate this barrier to patient care. This study assessed the diagnostic accuracy of SUB by trainees versus formal ultrasonographer or computed tomography examination for suspected symptomatic cholelithiasis. A prospective non-inferiority study of emergency patient admissions with abdominal pain in two tertiary referral hospitals during July 2017 to October 2018 was performed. Results of SUB were compared with accredited radiographer ultrasonography or computed tomography and histopathological assessment. Positive findings at SUB for symptomatic cholelithiasis included: cholelithiasis, gallbladder wall thickness ˃3 mm, pericholecystic fluid or sonographic Murphy's sign. One hundred patients with epigastric or right upper quadrant pain underwent SUB. Mean patient age was 49 years (range 20-90 years), with 61 females and 39 males. Sensitivity and specificity for diagnosis of symptomatic cholelithiasis was 94.9% and 100% for SUB and 98.7% and 100% for accredited radiographers. Diagnostic accuracy was 96% for SUB and 99% for radiographer ultrasonography. Positive predictive value and negative predictive value were 100% and 84.6% for SUB and 100% and 96% for radiographers. The inter-rater reliability for features compatible with the diagnosis of symptomatic cholelithiasis was good with a kappa of 0.758 (95% confidence interval 0.587-0.929, P < 0.001). This first Australian experience demonstrates that general surgical trainees can accurately diagnose cholecystitis with SUB and this assessment is not inferior and has substantial agreement with accredited radiographer ultrasonography.
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Best practise care optimises survival and quality of life in patients with pancreatic cancer (PC), but there is evidence of variability in management and suboptimal care for some patients. Monitoring practise is necessary to underpin... more
Best practise care optimises survival and quality of life in patients with pancreatic cancer (PC), but there is evidence of variability in management and suboptimal care for some patients. Monitoring practise is necessary to underpin improvement initiatives. We aimed to develop a core set of quality indicators that measure quality of care across the disease trajectory. A modified, three-round Delphi survey was performed among experts with wide experience in PC care across three states in Australia. A total of 107 potential quality indicators were identified from the literature and divided into five areas: diagnosis and staging, surgery, other treatment, patient management and outcomes. A further six indicators were added by the panel, increasing potential quality indicators to 113. Rated on a scale of 1-9, indicators with high median importance and feasibility (score 7-9) and low disagreement (<1) were considered in the candidate set. From 113 potential quality indicators, 34 ind...
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Palliative chemotherapy improves symptom control and prolongs survival in patients with unresectable pancreatic cancer, but there is a paucity of data describing its use and effectiveness in everyday practice. We explored patterns of... more
Palliative chemotherapy improves symptom control and prolongs survival in patients with unresectable pancreatic cancer, but there is a paucity of data describing its use and effectiveness in everyday practice. We explored patterns of chemotherapy use in patients with unresected pancreatic cancer in Australia and the impact of use on survival. We reviewed the medical records of residents of New South Wales or Queensland, Australia, diagnosed with unresectable pancreatic adenocarcinoma between July 2009 and June 2011. Associations between receipt of chemotherapy and sociodemographic, clinical and health service factors were evaluated using logistic regression. We used Cox proportional hazards models to analyze associations between chemotherapy use and survival. Data were collected for 1173 eligible patients. Chemotherapy was received by 44% (n = 184/414) of patients with localized pancreatic cancer and 53% (n = 406/759) of patients with metastases. Chemotherapy receipt depended on cli...
Periampullary cancers include pancreatic, ampullary, biliary and duodenal cancers. At presentation, the majority of periampullary tumours have grown to involve the pancreas, bile duct, ampulla and duodenum. This can result in difficulty... more
Periampullary cancers include pancreatic, ampullary, biliary and duodenal cancers. At presentation, the majority of periampullary tumours have grown to involve the pancreas, bile duct, ampulla and duodenum. This can result in difficulty in defining the primary site of origin in all but the smallest tumors due to anatomical proximity and architectural distortion. This has led to variation in the reported proportions of resected periampullary cancers. Pancreatic cancer is the most common cancer resected with a pancreaticoduodenectomy followed by ampullary (16%-50%), bile duct (5%-39%), and duodenal cancer (3%-17%). Patients with resected duodenal and ampullary cancers have a better reported median survival (29-47 mo and 22-54 mo) compared to pancreatic cancer (13-19 mo). The poorer survival with pancreatic cancer relates to differences in tumour characteristics such as a higher incidence of nodal, neural and vascular invasion. While small ampullary cancers can present early with bilia...
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The return of research results (RoR) remains a complex and well-debated issue. Despite the debate, actual data related to the experience of giving individual results back, and the impact these results may have on clinical care and health... more
The return of research results (RoR) remains a complex and well-debated issue. Despite the debate, actual data related to the experience of giving individual results back, and the impact these results may have on clinical care and health outcomes, is sorely lacking. Through the work of the Australian Pancreatic Cancer Genome Initiative (APGI) we: (1) delineate the pathway back to the patient where actionable research data were identified; and (2) report the clinical utilisation of individual results returned. Using this experience, we discuss barriers and opportunities associated with a comprehensive process of RoR in large-scale genomic research that may be useful for others developing their own policies. We performed whole-genome (n = 184) and exome (n = 208) sequencing of matched tumour-normal DNA pairs from 392 patients with sporadic pancreatic cancer (PC) as part of the APGI. We identified pathogenic germline mutations in candidate genes (n = 130) with established predispositio...
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We retrospectively evaluated the value of PET/CT in predicting survival and histopathological tumour-response in patients with distal oesophageal and gastric adenocarcinoma following neoadjuvant treatment. Twenty-one patients with... more
We retrospectively evaluated the value of PET/CT in predicting survival and histopathological tumour-response in patients with distal oesophageal and gastric adenocarcinoma following neoadjuvant treatment. Twenty-one patients with resectable distal oesophageal adenocarcinoma and 14 with gastric adenocarcinoma between January 2002 and December 2011, who had undergone serial PET before and after neoadjuvant therapy followed by surgery, were enrolled. Maximum standard uptake value (SUVmax) and metabolic tumour volume were measured and correlated with tumour regression grade and survival. Histopathological tumour response (PR) is a stronger predictor of overall and disease-free survival compared to metabolic response. ∆%SUVmax ≥70% was the only PET metric that predicted PR (82.4% sensitivity, 61.5% specificity, p = 0.047). Histopathological non-responders had a higher risk of death (HR 8.461, p = 0.001) and recurrence (HR 6.385, p = 0.002) and similarly in metabolic non-responders for d...
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To examine differences in the proportions of people diagnosed with pancreatic cancer who underwent pancreatectomy, post-operative outcomes and 5-year survival in different New South Wales administrative health regions of residence.... more
To examine differences in the proportions of people diagnosed with pancreatic cancer who underwent pancreatectomy, post-operative outcomes and 5-year survival in different New South Wales administrative health regions of residence. Retrospective analysis of NSW data on pancreatic cancer incidence and surgery, 2005-2013. The proportion of newly diagnosed patients with pancreatic cancer who were resected in each region; 90-day post-operative mortality; one-year post-operative survival; 5-year post-diagnosis survival. 14% of people diagnosed with pancreatic cancer during 2010-2013 (431 of 3064) underwent pancreatectomy, an average of 108 resections per year. After adjusting for age, sex and comorbidities, the proportion that underwent resection varied significantly between regions, ranging between 8% and 21% (P<0.001). Higher resection rates were not associated with higher post-operative 90-day mortality or lower one-year survival (unadjusted and risk-adjusted analyses). Higher rese...
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The diagnosis of pancreatic neuroendocrine tumours (PanNETs) is increasing owing to more sensitive detection methods, and this increase is creating challenges for clinical management. We performed whole-genome sequencing of 102 primary... more
The diagnosis of pancreatic neuroendocrine tumours (PanNETs) is increasing owing to more sensitive detection methods, and this increase is creating challenges for clinical management. We performed whole-genome sequencing of 102 primary PanNETs and defined the genomic events that characterize their pathogenesis. Here we describe the mutational signatures they harbour, including a deficiency in G:C > T:A base excision repair due to inactivation of MUTYH, which encodes a DNA glycosylase. Clinically sporadic PanNETs contain a larger-than-expected proportion of germline mutations, including previously unreported mutations in the DNA repair genes MUTYH, CHEK2 and BRCA2. Together with mutations in MEN1 and VHL, these mutations occur in 17% of patients. Somatic mutations, including point mutations and gene fusions, were commonly found in genes involved in four main pathways: chromatin remodelling, DNA damage repair, activation of mTOR signalling (including previously undescribed EWSR1 ge...
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People with pancreatic cancer have high levels of anxiety and depression and reduced quality of life (QoL), but few studies have assessed these outcomes for patient-carer dyads. We therefore investigated these issues in an Australian... more
People with pancreatic cancer have high levels of anxiety and depression and reduced quality of life (QoL), but few studies have assessed these outcomes for patient-carer dyads. We therefore investigated these issues in an Australian population-based study. Patients with pancreatic cancer (n = 136) and many of their carers (n = 84) completed the Hospital Anxiety and Depression Scale (HADS) and Functional Assessment of Cancer Therapy QoL questionnaire at a median of three months after diagnosis. Overall QoL and well-being subscales (physical, social, emotional, functional) were compared with general population norms. Intraclass correlation coefficients were used to compare anxiety, depression and QoL scores of patients and their respective carers. Fifteen percent of patients and 39% of carers had HADS scores indicative of anxiety and 15% of patients and 14% of carers of depression, respectively. Overall, 70% of patients and 58% of carers had QoL scores below the Queensland population...
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To develop a composite score for the quality of care for patients with pancreatic cancer in Australia; to determine whether it was affected by patient and health service-related factors; to assess whether the score and survival were... more
To develop a composite score for the quality of care for patients with pancreatic cancer in Australia; to determine whether it was affected by patient and health service-related factors; to assess whether the score and survival were correlated. We reviewed medical records of patients diagnosed with pancreatic cancer during July 2009 - June 2011 and notified to the Queensland and New South Wales cancer registries. Participants were allocated proportional quality of care scores based on indicators derived from a Delphi process, ranging from 0 (lowest) to 1 (highest quality care). Associations between patient and health service-related factors and the score were tested by linear regression, and associations between the score and survival with Kaplan-Meier and Cox proportional hazards methods. Proportional quality of care scores were assigned to 1571 patients. Scores for patients living in rural areas were significantly lower than for those in major cities (adjusted difference, 11%; 95%...
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This study aims to determine if the supportive care needs of people with pancreatic cancer change over time and identify the factors associated with current and future unmet needs. Australian pancreatic cancer patients completed a... more
This study aims to determine if the supportive care needs of people with pancreatic cancer change over time and identify the factors associated with current and future unmet needs. Australian pancreatic cancer patients completed a self-administered survey at 0-6 months post-diagnosis (n = 116) then follow-up surveys 2 (n = 82) and 4 months (n = 50) later. The validated survey measured 34 needs across five domains. Weighted generalised estimating equations were used to identify factors associated with having ≥1 current or future moderate-to-high unmet need. The overall proportion of patients reporting ≥1 moderate-or-high-level need did not significantly change over time (baseline = 70 % to 4 months = 75 %), although there was a non-significant reduction in needs for patients who had a complete resection (71 to 63 %) and an increase in patients with locally advanced (73 to 85 %) or metastatic (66 to 88 %) disease. Higher levels of pain (OR 6.1, CI 2.4-15.3), anxiety (OR 3.3, CI 1.5-7....
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Intraoperative decompression of the small bowel has been advocated as a method of aiding recovery of both the patient and the intestine. However, the methods proposed (retrograde stripping or enterotomy) require vigorous handling of... more
Intraoperative decompression of the small bowel has been advocated as a method of aiding recovery of both the patient and the intestine. However, the methods proposed (retrograde stripping or enterotomy) require vigorous handling of bacteria-laden small bowel, possibly giving rise to a bacteremia. A small bowel obstruction was created in 31 rats by means of a ligature. Twenty-four hours later, the obstruction was relieved, and the rats were divided into three groups: relief of obstruction alone, relief with retrograde stripping, and relief with enterotomy plus suction. Blood cultures were taken before and after manipulation of the bowel. In blood cultures taken before and after manipulation there was a significant increase of Escherichia coli bacteremia in the two manipulation groups compared with the relief of obstruction only group. Bacteremia may be an effect of operative decompression of obstructed bowel, which at times outweighs its supposed benefits.
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Integrated genomic analysis of 456 pancreatic ductal adenocarcinomas identified 32 recurrently mutated genes that aggregate into 10 pathways: KRAS, TGF-β, WNT, NOTCH, ROBO/SLIT signalling, G1/S transition, SWI-SNF, chromatin modification,... more
Integrated genomic analysis of 456 pancreatic ductal adenocarcinomas identified 32 recurrently mutated genes that aggregate into 10 pathways: KRAS, TGF-β, WNT, NOTCH, ROBO/SLIT signalling, G1/S transition, SWI-SNF, chromatin modification, DNA repair and RNA processing. Expression analysis defined 4 subtypes: (1) squamous; (2) pancreatic progenitor; (3) immunogenic; and (4) aberrantly differentiated endocrine exocrine (ADEX) that correlate with histopathological characteristics. Squamous tumours are enriched for TP53 and KDM6A mutations, upregulation of the TP63∆N transcriptional network, hypermethylation of pancreatic endodermal cell-fate determining genes and have a poor prognosis. Pancreatic progenitor tumours preferentially express genes involved in early pancreatic development (FOXA2/3, PDX1 and MNX1). ADEX tumours displayed upregulation of genes that regulate networks involved in KRAS activation, exocrine (NR5A2 and RBPJL), and endocrine differentiation (NEUROD1 and NKX2-2). Im...
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Virtual reality surgical simulators have proven value in the acquisition and assessment of laparoscopic skills. In this study, we investigated skill transfer from a virtual reality laparoscopic simulator into the operating room, using a... more
Virtual reality surgical simulators have proven value in the acquisition and assessment of laparoscopic skills. In this study, we investigated skill transfer from a virtual reality laparoscopic simulator into the operating room, using a blinded, randomised, controlled trial design. Surgical trainees using the LapSim System performed significantly better at their first real-world attempt at a laparoscopic task than their colleagues who had not received similar training, as measured independently by a number of expert surgical observers using four criteria.
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This is a reprint of a Cochrane protocol, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library 2008, Issue 4 http://www.thecochranelibrary.com ... Feasibility, safety and efficacy of laparoscopy and... more
This is a reprint of a Cochrane protocol, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library 2008, Issue 4 http://www.thecochranelibrary.com ... Feasibility, safety and efficacy of laparoscopy and laparoscopy-assisted vs. open surgery for acute small bowel obstruction in adults (Protocol) Copyright © 2008 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. ... Feasibility, safety and efficacy of laparoscopy and laparoscopy-assisted vs. open surgery for acute small bowel obstruction in adults ( ...
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ABSTRACT The novel biomarker HoxB2 predicts response to pancreatectomy for pancreatic cancer Eur J Cancer (suppl) 2007; 5 (4) 264
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A case of torsion of the vermiform appendix is described. It is a rare cause of an acute abdomen with a clinical presentation that is indistinguishable from acute appendicitis.