ORCID Profile
0000-0002-6430-6741
Current Organisations
Tunnell Government Services
,
Monash University
,
Monash Health
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Publisher: Springer Science and Business Media LLC
Date: 02-06-2020
DOI: 10.1038/S41541-020-0191-8
Abstract: The Sementis Copenhagen Vector (SCV) is a new vaccinia virus-derived, multiplication-defective, vaccine technology assessed herein in non-human primates. Indian rhesus macaques ( Macaca mulatta ) were vaccinated with a multi-pathogen recombinant SCV vaccine encoding the structural polyproteins of both Zika virus (ZIKV) and chikungunya virus (CHIKV). After one vaccination, neutralising antibody responses to ZIKV and four strains of CHIKV, representative of distinct viral genotypes, were generated. A second vaccination resulted in significant boosting of neutralising antibody responses to ZIKV and CHIKV. Following challenge with ZIKV, SCV-ZIKA/CHIK-vaccinated animals showed significant reductions in viremias compared with animals that had received a control SCV vaccine. Two SCV vaccinations also generated neutralising and IgG ELISA antibody responses to vaccinia virus. These results demonstrate effective induction of immunity in non-human primates by a recombinant SCV vaccine and illustrates the utility of SCV as a multi-disease vaccine platform capable of delivering multiple large immunogens.
Publisher: Royal College of Surgeons of England
Date: 11-2015
Abstract: The acute surgical model has been trialled in several institutions with mixed results. The aim of this study was to determine whether the acute surgical model provides better outcomes for patients with acute biliary presentation, compared with the traditional emergency surgery model of care. A retrospective review was carried out of patients who were admitted for management of acute biliary presentation, before and after the establishment of an acute surgical unit (ASU). Outcomes measured were time to operation, operating time, after-hours operation (6pm – 8am), length of stay and surgical complications. A total of 342 patients presented with acute biliary symptoms and were managed operatively. The median time to operation was significantly reduced in the ASU group (32.4 vs 25.4 hours, p=0.047), as were the proportion of operations performed after hours (19.5% vs 2.5%, p .001) and the median length of stay (4 vs 3 days, p .001). The median operating time, rate of conversion to open cholecystectomy and wound infection rates remained similar. Implementation of an ASU can lead to objective differences in outcomes for patients who present with acute cholecystitis. In our study, the ASU significantly reduced time to operation, the number of operations performed after hours and length of stay.
Publisher: Wiley
Date: 14-07-2017
DOI: 10.1111/ANS.13217
Abstract: This study examines the usefulness of early post-operative liver function test (LFT) monitoring in predicting retained choledocholithiasis after laparoscopic common bile duct exploration (LCBDE). Data on patients who had LCBDE over a 3-year period were collected retrospectively. Patients who had ongoing choledocholithiasis after unsuccessful LCBDE were considered for the test group and patients who had successful LCBDE were considered for the control group. Preoperative, day 1 post-operative and day 2 post-operative alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), alanine transaminase (ALT) and bilirubin levels were recorded. Proportions of patients who had worsening LFTs were analysed in each group. Proportions of patient who had worsening LFTs on day 1 were not statistically different between two groups and they were statistically equal on equivalence testing (two one-sided tests). On day 2, proportions of patient were again not statistically different. Bilirubin and ALT were statistically equivalent (P = 0.022 and P = 0.025 respectively) but GGT and ALP failed to achieve statistical equivalence (P = 0.062 and P = 0.138 respectively) on day 2. Twelve patients with normal appearing final intraoperative cholangiogram needed reintervention due to retained choledocholithiasis diagnosed subsequently. LFTs progressively improved despite presence of choledocholithiasis in eight of these 12 patients (75%) and only four were diagnosed by worsening post-operative LFTs during index admission. LFTs in the early post-operative period are not useful in determining which patients require biliary imaging or intervention after an apparently successful LCBDE.
Publisher: Elsevier BV
Date: 08-2022
DOI: 10.1016/J.HPB.2022.01.011
Abstract: Pancreatic ductal adenocarcinoma (PDAC) has poor survival. Current treatments offer little likelihood of cure or long-term survival. This systematic review evaluates prognostic models predicting overall survival in patients diagnosed with PDAC. We conducted a comprehensive search of eight electronic databases from their date of inception through to December 2019. Studies that published models predicting survival in patients with PDAC were identified. 3297 studies were identified 187 full-text articles were retrieved and 54 studies of 49 unique prognostic models were included. Of these, 28 (57.1%) were conducted in patients with advanced disease, 17 (34.7%) with resectable disease, and four (8.2%) in all patients. 34 (69.4%) models were validated, and 35 (71.4%) reported model discrimination, with only five models reporting values >0.70 in both derivation and validation cohorts. Many (n = 27) had a moderate to high risk of bias and most (n = 33) were developed using retrospective data. No variables were unanimously found to be predictive of survival when included in more than one study. Most prognostic models were developed using retrospective data and performed poorly. Future research should validate instruments performing well locally in international cohorts and investigate other potential predictors of survival.
Publisher: Royal Society of Chemistry (RSC)
Date: 2013
DOI: 10.1039/C3SM50646K
Publisher: Informa UK Limited
Date: 2008
DOI: 10.1080/00365520802102489
Abstract: The molecular and cellular events responsible for regulating development of the oesophageal epithelium are not well understood. At least in part, this is due to the lack of a suitable model system with which to study the process. Here, we report development of a manipulable in vivo transplant model for mouse or human oesophageal epithelium. Epithelial cells were isolated from mouse or human oesophagus and inoculated into de-epithelialized and devitalized rat tracheas. The rat trachea, containing cells, was placed subcutaneously under the dorsal skin of immunodeficient mice. We show that a multilayered stratified squamous epithelium can be generated in 4-6 weeks from as few as 5 x 10(4) isolated oesophageal epithelial cells. The reconstituted epithelium recapitulates many of the structural and histological features of the normal oesophageal epithelium, including a basal layer of cuboidal-like cells, suprabasal layers of differentiating squamous cells and, in the case of murine cells, a superficial layer of cornified material. Our model can be used to generate a multilayered normal murine or human epithelium from a single cell suspension of oesophageal epithelial cells. The ability to genetically manipulate the cells prior to growth in the model is a powerful tool with which to study the molecular mechanisms involved in the development of normal oesophagus or in pathogenic processes such as Barrett's metaplasia or tumorigenesis.
Publisher: Wiley
Date: 28-02-2017
DOI: 10.1002/IJC.30648
Abstract: Pancreatic cancer (PC) is largely refractory to existing therapies used in unselected patient trials, thus emphasizing the pressing need for new approaches for patient selection in personalized medicine. KRAS mutations occur in 90% of PC patients and confer resistance to epidermal growth factor receptor (EGFR) inhibitors (e.g., panitumumab), suggesting that KRAS wild-type PC patients may benefit from targeted panitumumab therapy. Here, we use tumor tissue procured by endoscopic ultrasound-guided fine-needle aspirate (EUS-FNA) to compare the in vivo sensitivity in patient-derived xenografts (PDXs) of KRAS wild-type and mutant PC tumors to panitumumab, and to profile the molecular signature of these tumors in patients with metastatic or localized disease. Specifically, RNASeq of EUS-FNA-derived tumor RNA from localized (n = 20) and metastatic (n = 20) PC cases revealed a comparable transcriptome profile. Screening the KRAS mutation status of tumor genomic DNA obtained from EUS-FNAs stratified PC patients into either KRAS wild-type or mutant cohorts, and the engraftment of representative KRAS wild-type and mutant EUS-FNA tumor s les into NOD/SCID mice revealed that the growth of KRAS wild-type, but not mutant, PDXs was selectively suppressed with panitumumab. Furthermore, in silico transcriptome interrogation of The Cancer Genome Atlas (TCGA)-derived KRAS wild-type (n = 38) and mutant (n = 132) PC tumors revealed 391 differentially expressed genes. Taken together, our study validates EUS-FNA for the application of a novel translational pipeline comprising KRAS mutation screening and PDXs, applicable to all PC patients, to evaluate personalized anti-EGFR therapy in patients with KRAS wild-type tumors.
Publisher: Wiley
Date: 28-03-2016
DOI: 10.1111/ANS.13496
Publisher: Wiley
Date: 12-2016
DOI: 10.1111/ANS.13770
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.22481507.V1
Abstract: Supplementary tables and figure
Publisher: Informa UK Limited
Date: 28-08-2017
DOI: 10.1080/14737140.2017.1369882
Abstract: Despite recent progress, the outlook for most patients with pancreatic cancer remains poor. There is variation in how patients are managed globally due to differing interpretations of the evidence, partly because studies in this disease are challenging to undertake. This article collates the evidence upon which current best practice is based and offers an expert opinion from an international faculty on how latest developments should influence current treatment paradigms. Areas covered: Optimal chemotherapy for first and subsequent lines of therapy optimal management of locally advanced, non-metastatic cancer including the role of neoadjuvant chemo(radio)therapy, current evidence for adjuvant chemotherapy, major advances in pancreatic cancer genomics and challenges in supportive care particularly relevant to patients with pancreatic cancer. For each section, literature was reviewed by comprehensive search techniques, including clinical trial websites and abstracts from international cancer meetings. Expert commentary: For each section, a commentary is provided. Overall the challenges identified were: difficulties in diagnosing pancreatic cancer early, challenges for performing randomised clinical trials in all stages of the disease, some progress in systemic therapy with new agents and in identifying molecular subtypes that may be clinically relevant and move towards personalized therapy, but still, pancreatic cancer remains a very poor prognosis cancer with significant palliative care needs.
Publisher: Elsevier BV
Date: 07-2023
Publisher: Wiley
Date: 09-2014
DOI: 10.1111/NYAS.12521
Abstract: The following, from the 12th OESO World Conference: Cancers of the Esophagus, includes commentaries on the relationship between stem cells, cancer, and the esophagus the behavior of esophageal stem cells and the role of genetics and epigenetics in approaches to translational research.
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.C.6530708.V1
Abstract: AbstractPurpose: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with a poor prognosis, and current diagnostic tests have suboptimal sensitivity. Incorporating standard cytology with targeted transcriptomic and mutation analysis may improve upon the accuracy of diagnostic biopsies, thus reducing the burden of repeat procedures and delays to treatment initiation. Experimental Design: We reviewed the accuracy of 308 endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) diagnostic PDAC biopsies using a large multicenter clinical and biospecimen database, then performed RNA sequencing on 134 EUS-FNA biopsies spanning all stages of disease. We identified a transcriptomic diagnostic gene signature that was validated using external datasets and 60 further diagnostic EUS-FNAs. i KRAS /i digital droplet PCR (ddPCR) analysis was performed and correlated with signature gene expression. Results: The sensitivity of EUS-FNA cytology in diagnosing solid pancreatic masses in our retrospective cohort of 308 patients was 78.6% (95% confidence interval, 73.2%–83.2%). i KRAS /i mutation analysis and our custom transcriptomic signature significantly improved upon the diagnostic accuracy of standard cytology to 91.3% in external validation sets and 91.6% in our validation cohort ( i n /i = 60). Exploratory ddPCR analysis of i KRAS /i -mutant allele fraction (MAF%) correlated closely to signature performance and may represent a novel surrogate marker of tumor cellularity in snap-frozen EUS-FNA biopsies. Conclusions: Our findings support snap-frozen EUS-FNA biopsies as a feasible tissue source for the integrated genomic and transcriptomic analysis of patients presenting with PDAC from all tumor stages, including cases with nondiagnostic cytology. Our transcriptome-derived genetic signature in combination with tissue i KRAS /i mutation analysis significantly improves upon the diagnostic accuracy of current standard procedures, and has potential clinical utility in improving the speed and accuracy of diagnosis for patients presenting with PDAC. /
Publisher: Wiley
Date: 11-02-2015
DOI: 10.1111/ASES.12174
Abstract: Postoperative abnormal liver function tests (LFT) following laparoscopic cholecystectomy (LC) could present a substantial clinical dilemma due to suspicion of missed choledocholithiasis or more serious complications such as bile duct injury. We noted that LFT were more likely to be abnormal when an intraoperative cholangiogram (IOC) had been performed. This study aims to examine if contrast injection into the biliary tract during IOC is associated with deranged LFT. Data on all LC performed in a tertiary referral hospital network over a period of 30 months were collected retrospectively, and two groups were identified depending on successful performance of an IOC. Identical inclusion and exclusion criteria were applied to both groups to identify eligible patients. Alkaline phosphatase, gamma-glutamyl transferase (GGT), alanine transaminase (ALT), and bilirubin levels were recorded, and the mean difference between preoperative and postoperative values was analyzed. There were 177 eligible patients: 147 patients in the LC with IOC test group (IOC group) and 30 patients in the LC without IOC control group (NO IOC group). Demographics and preoperative mean LFT were not significantly different between groups. In the IOC group, the mean ALT difference (43 ± 57, P =< 0.001) and GGT difference (34 ± 66, P =< 0.001) were significantly higher than in the NO IOC group (ALT [19 ± 25], GGT [7 ± 20]). The mean alkaline phosphatase difference (IOC [9 ± 47], NO IOC [-2 ± 14], P = 0.214) and mean bilirubin difference (IOC [-2 ± 9], NO IOC [-1 ± 8], P = 0.911) were not significantly different. The performance of an IOC is associated with elevated GGT and ALT but does not affect alkaline phosphatase and bilirubin concentrations.
Publisher: American Association for Cancer Research (AACR)
Date: 16-08-2021
DOI: 10.1158/1078-0432.CCR-21-1107
Abstract: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with a poor prognosis, and current diagnostic tests have suboptimal sensitivity. Incorporating standard cytology with targeted transcriptomic and mutation analysis may improve upon the accuracy of diagnostic biopsies, thus reducing the burden of repeat procedures and delays to treatment initiation. We reviewed the accuracy of 308 endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) diagnostic PDAC biopsies using a large multicenter clinical and biospecimen database, then performed RNA sequencing on 134 EUS-FNA biopsies spanning all stages of disease. We identified a transcriptomic diagnostic gene signature that was validated using external datasets and 60 further diagnostic EUS-FNAs. KRAS digital droplet PCR (ddPCR) analysis was performed and correlated with signature gene expression. The sensitivity of EUS-FNA cytology in diagnosing solid pancreatic masses in our retrospective cohort of 308 patients was 78.6% (95% confidence interval, 73.2%–83.2%). KRAS mutation analysis and our custom transcriptomic signature significantly improved upon the diagnostic accuracy of standard cytology to 91.3% in external validation sets and 91.6% in our validation cohort (n = 60). Exploratory ddPCR analysis of KRAS-mutant allele fraction (MAF%) correlated closely to signature performance and may represent a novel surrogate marker of tumor cellularity in snap-frozen EUS-FNA biopsies. Our findings support snap-frozen EUS-FNA biopsies as a feasible tissue source for the integrated genomic and transcriptomic analysis of patients presenting with PDAC from all tumor stages, including cases with nondiagnostic cytology. Our transcriptome-derived genetic signature in combination with tissue KRAS mutation analysis significantly improves upon the diagnostic accuracy of current standard procedures, and has potential clinical utility in improving the speed and accuracy of diagnosis for patients presenting with PDAC.
Publisher: Springer Science and Business Media LLC
Date: 05-08-2008
DOI: 10.1007/S12015-008-9031-3
Abstract: The incidence of adenocarcinoma of the esophagus has increased faster than any other internal malignancy over the last 40 years. Despite this, surprisingly little is known about the basic biology of this tissue, particularly with regards to the organization of cell proliferation within the epithelium. This is a matter of crucial importance for our understanding of the pathogenesis of esophageal cancer. Nevertheless, significant advances have recently been made in the identification and functional characterization of both murine and human esophageal stem cells and their progeny in recent years. This places investigators in an exciting position to gain further insights into the processes of tissue renewal and repair on the one hand and the development of dysplasia and malignancy on the other.
Publisher: Georg Thieme Verlag KG
Date: 30-01-2017
Publisher: Elsevier BV
Date: 2022
DOI: 10.1016/J.MOLCEL.2021.11.015
Abstract: Mediator kinases (CDK8/19) are transcriptional regulators broadly implicated in cancer. Despite their central role in fine-tuning gene-expression programs, we find complete loss of CDK8/19 is tolerated in colorectal cancer (CRC) cells. Using orthogonal functional genomic and pharmacological screens, we identify BET protein inhibition as a distinct vulnerability in CDK8/19-depleted cells. Combined CDK8/19 and BET inhibition led to synergistic growth retardation in human and mouse models of CRC. Strikingly, depletion of CDK8/19 in these cells led to global repression of RNA polymerase II (Pol II) promoter occupancy and transcription. Concurrently, loss of Mediator kinase led to a profound increase in MED12 and BRD4 co-occupancy at enhancer elements and increased dependence on BET proteins for the transcriptional output of cell-essential genes. In total, this work demonstrates a synthetic lethal interaction between Mediator kinase and BET proteins and exposes a therapeutic vulnerability that can be targeted using combination therapies.
Publisher: Wiley
Date: 31-08-2016
DOI: 10.1111/ANS.13724
Abstract: A significant proportion of general surgery emergency procedures are conducted after‐hours in regional centres. The acute surgical unit (ASU) model reduces the number of after‐hours operations performed. We review the burden of emergency surgery in a regional centre and assess what components of the ASU model would benefit regional hospitals. Retrospective analysis was performed on data for all emergency cases performed at Latrobe Regional Hospital (LRH) over a 1‐year period. Time into and out of theatre was used to determine total theatre usage and if the operation occurred after‐hours. ED triage time to theatre and start time for appendicectomy was compared to data from our metropolitan referral hospital, Monash Medical Centre (MMC), which has employed an ASU. General surgery emergency cases in regional areas are regular and predictable with a median of two emergency cases performed, and a mean theatre time of 156 min per day at LRH. On weekdays, 43.1% ( n = 503) of emergency cases were done in the evening (18.00–24.00 hours), compared to 20.3% ( n = 217) on weekends when an emergency theatre is available during the day. LRH performed more appendicectomies after‐hours than MMC over a 1‐year period. Regional centres have a significant burden of general surgery emergency procedures of which the number performed after‐hours is comparable to metropolitan centres. The number of procedures and theatre time required by these cases justify a dedicated emergency theatre in‐hours similar to metropolitan ASU models and this would reduce emergency operating after‐hours.
Publisher: Wiley
Date: 12-2014
DOI: 10.1111/ANS.12871
Publisher: Wiley
Date: 05-10-2017
DOI: 10.1111/ANS.14211
Publisher: Wiley
Date: 10-2013
DOI: 10.1111/ANS.12351
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.C.6530708
Abstract: AbstractPurpose: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with a poor prognosis, and current diagnostic tests have suboptimal sensitivity. Incorporating standard cytology with targeted transcriptomic and mutation analysis may improve upon the accuracy of diagnostic biopsies, thus reducing the burden of repeat procedures and delays to treatment initiation. Experimental Design: We reviewed the accuracy of 308 endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) diagnostic PDAC biopsies using a large multicenter clinical and biospecimen database, then performed RNA sequencing on 134 EUS-FNA biopsies spanning all stages of disease. We identified a transcriptomic diagnostic gene signature that was validated using external datasets and 60 further diagnostic EUS-FNAs. i KRAS /i digital droplet PCR (ddPCR) analysis was performed and correlated with signature gene expression. Results: The sensitivity of EUS-FNA cytology in diagnosing solid pancreatic masses in our retrospective cohort of 308 patients was 78.6% (95% confidence interval, 73.2%–83.2%). i KRAS /i mutation analysis and our custom transcriptomic signature significantly improved upon the diagnostic accuracy of standard cytology to 91.3% in external validation sets and 91.6% in our validation cohort ( i n /i = 60). Exploratory ddPCR analysis of i KRAS /i -mutant allele fraction (MAF%) correlated closely to signature performance and may represent a novel surrogate marker of tumor cellularity in snap-frozen EUS-FNA biopsies. Conclusions: Our findings support snap-frozen EUS-FNA biopsies as a feasible tissue source for the integrated genomic and transcriptomic analysis of patients presenting with PDAC from all tumor stages, including cases with nondiagnostic cytology. Our transcriptome-derived genetic signature in combination with tissue i KRAS /i mutation analysis significantly improves upon the diagnostic accuracy of current standard procedures, and has potential clinical utility in improving the speed and accuracy of diagnosis for patients presenting with PDAC. /
Publisher: MDPI AG
Date: 10-10-2022
Abstract: Background: KRAS G12D mutation subtype is present in over 40% of pancreatic ductal adenocarcinoma (PDAC), one of the leading global causes of cancer death. This retrospective cohort study aims to investigate whether detection of the KRAS G12D mutation subtype in PDAC patients is a determinant of prognosis across all stages of disease. Methods: We reviewed the medical records of 231 patients presenting with PDAC at a large tertiary hospital, and compared survival using the Kaplan Meier, log-rank test and Cox proportional hazards regression model. Results: KRAS G12D mutation subtype was not significantly associated with poorer survival compared across the whole population of PDAC patients (p = 0.107 HR 1.293 95% CI (0.946–1.767)). However, KRAS G12D patients who were resectable had a shorter median survival time of 356 days compared to all other genotypes (median survival 810 days) (p = 0.019 HR 1.991 95% CI (1.121–3.537)). Conclusions: KRAS G12D patients who were resectable at diagnosis had shorter survival compared to all other PDAC patients. These data suggest that KRAS G12D may be a clinically useful prognostic biomarker of PDAC.
Publisher: JMIR Publications Inc.
Date: 30-08-2020
Abstract: dults diagnosed with cancers of the stomach, esophagus, and pancreas are at high risk of malnutrition. In many hospital-based health care settings, there is a lack of systems in place to provide the early and intensive nutritional support that is required by these high-risk cancer patients. Our research team conducted a 3-arm parallel randomized controlled trial to test the provision of an early and intensive nutrition intervention to patients with upper gastrointestinal cancers using a synchronous telephone-based delivery approach versus an asynchronous mobile app–based approach delivered using an iPad compared with a control group to address this issue. his study aims to explore the overall acceptability of an early and intensive eHealth nutrition intervention delivered either via a synchronous telephone-based approach or an asynchronous mobile app–based approach. atients who were newly diagnosed with upper gastrointestinal cancer and who consented to participate in a nutrition intervention were recruited. In-depth, semistructured qualitative interviews were conducted by telephone and transcribed verbatim. Data were analyzed using deductive thematic analysis using the Theoretical Framework of Acceptability in NVivo Pro 12 Plus. total of 20 participants were interviewed, 10 from each intervention group (synchronous or asynchronous delivery). Four major themes emerged from the qualitative synthesis: participants’ self-efficacy, low levels of burden, and intervention comprehension were required for intervention effectiveness and positive affect participants sought a sense of support and security through relationship building and rapport with their dietitian knowledge acquisition and learning-enabled empowerment through self-management and convenience, flexibility, and bridging the gap to hard-to-reach in iduals. eatures of eHealth models of nutrition care delivered via telephone and mobile app can be acceptable to those undergoing treatment for upper gastrointestinal cancer. Convenience, knowledge acquisition, improved self-management, and support were key benefits for the participants. Future interventions should focus on home-based interventions delivered with simple, easy-to-use technology. Providing participants with a choice of intervention delivery mode (synchronous or asynchronous) and allowing them to make in idual choices that align to their in idual values and capabilities may support improved outcomes. ustralian and New Zealand Clinical Trial Registry (ACTRN) 12617000152325 3kxd37b.
Publisher: Wiley
Date: 04-2017
DOI: 10.1111/ANS.13918
Publisher: Elsevier BV
Date: 12-2011
Publisher: Baishideng Publishing Group Inc.
Date: 2009
DOI: 10.3748/WJG.15.4849
Publisher: Elsevier BV
Date: 07-2014
DOI: 10.1111/HPB.12187
Publisher: JMIR Publications Inc.
Date: 23-06-2020
DOI: 10.2196/16112
Abstract: Increased accessibility to the internet and mobile devices has seen a rapid expansion in electronic health (eHealth) behavior change interventions delivered to patients with cancer and survivors using synchronous, asynchronous, and combined delivery methods. Characterizing effective delivery methods of eHealth interventions is required to enable improved design and implementation of evidence-based health behavior change interventions. This study aims to systematically review the literature and synthesize evidence on the success of eHealth behavior change interventions in patients with cancer and survivors delivered by synchronous, asynchronous, or combined methods compared with a control group. Engagement with the intervention, behavior change, and health outcomes, including quality of life, fatigue, depression, and anxiety, were examined. A search of Scopus, Ovid MEDLINE, Excerpta Medica dataBASE, Cumulative Index to Nursing and Allied Health Literature Plus, PsycINFO, Cochrane CENTRAL, and PubMed was conducted for studies published between March 2007 and March 2019. We looked for randomized controlled trials (RCTs) examining interventions delivered to adult cancer survivors via eHealth methods with a measure of health behavior change. Random-effects meta-analysis was performed to examine whether the method of eHealth delivery impacted the level of engagement, behavior change, and health outcomes. A total of 24 RCTs were included predominantly examining dietary and physical activity behavior change interventions. There were 11 studies that used a synchronous approach and 11 studies that used an asynchronous approach, whereas 2 studies used a combined delivery method. Use of eHealth interventions improved exercise behavior (standardized mean difference [SMD] 0.34, 95% CI 0.21-0.48), diet behavior (SMD 0.44, 95% CI 0.18-0.70), fatigue (SMD 0.21, 95% CI −0.08 to 0.50 SMD change 0.22, 95% CI 0.09-0.35), anxiety (SMD 1.21, 95% CI: 0.36-2.07 SMD change 0.15, 95% CI −0.09 to 0.40), depression (SMD 0.15, 95% CI 0.00-0.30), and quality of life (SMD 0.12, 95% CI −0.10 to 0.34 SMD change 0.14, 95% CI 0.04-0.24). The mode of delivery did not influence the amount of dietary and physical activity behavior change observed. Physical activity and dietary behavior change eHealth interventions delivered to patients with cancer or survivors have a small to moderate impact on behavior change and a small to very small benefit to quality of life, fatigue, depression, and anxiety. There is insufficient evidence to determine whether asynchronous or synchronous delivery modes yield superior results. Three-arm RCTs comparing delivery modes with a control with robust engagement reporting are required to determine the most successful delivery method for promoting behavior change and ultimately favorable health outcomes.
Publisher: Elsevier BV
Date: 03-2009
Publisher: Wiley
Date: 08-2015
DOI: 10.1111/ANS.12341
Publisher: JMIR Publications Inc.
Date: 12-03-2021
DOI: 10.2196/23979
Abstract: Adults diagnosed with cancers of the stomach, esophagus, and pancreas are at high risk of malnutrition. In many hospital-based health care settings, there is a lack of systems in place to provide the early and intensive nutritional support that is required by these high-risk cancer patients. Our research team conducted a 3-arm parallel randomized controlled trial to test the provision of an early and intensive nutrition intervention to patients with upper gastrointestinal cancers using a synchronous telephone-based delivery approach versus an asynchronous mobile app–based approach delivered using an iPad compared with a control group to address this issue. This study aims to explore the overall acceptability of an early and intensive eHealth nutrition intervention delivered either via a synchronous telephone-based approach or an asynchronous mobile app–based approach. Patients who were newly diagnosed with upper gastrointestinal cancer and who consented to participate in a nutrition intervention were recruited. In-depth, semistructured qualitative interviews were conducted by telephone and transcribed verbatim. Data were analyzed using deductive thematic analysis using the Theoretical Framework of Acceptability in NVivo Pro 12 Plus. A total of 20 participants were interviewed, 10 from each intervention group (synchronous or asynchronous delivery). Four major themes emerged from the qualitative synthesis: participants’ self-efficacy, low levels of burden, and intervention comprehension were required for intervention effectiveness and positive affect participants sought a sense of support and security through relationship building and rapport with their dietitian knowledge acquisition and learning-enabled empowerment through self-management and convenience, flexibility, and bridging the gap to hard-to-reach in iduals. Features of eHealth models of nutrition care delivered via telephone and mobile app can be acceptable to those undergoing treatment for upper gastrointestinal cancer. Convenience, knowledge acquisition, improved self-management, and support were key benefits for the participants. Future interventions should focus on home-based interventions delivered with simple, easy-to-use technology. Providing participants with a choice of intervention delivery mode (synchronous or asynchronous) and allowing them to make in idual choices that align to their in idual values and capabilities may support improved outcomes. Australian and New Zealand Clinical Trial Registry (ACTRN) 12617000152325 3kxd37b.
Publisher: Wiley
Date: 09-10-2016
DOI: 10.1111/ANS.13790
Publisher: Wiley
Date: 05-12-2017
DOI: 10.1111/ANS.14280
Abstract: Studies have shown that post-operative telephone follow-up is satisfactory and effective. As high quality evidence is scant, we conducted a randomized controlled trial to compare it against outpatient clinic review for emergency laparoscopic appendicectomy or cholecystectomy. Patients who received emergency laparoscopic appendicectomy or cholecystectomy were eligible for this study. Once recruited, they were randomly allocated to either clinic review or telephone follow-up on discharge. Participants were reviewed at 2 weeks after operation and contacted again at 4 weeks after initial follow-up for satisfaction survey. One hundred and seventy-nine participants were recruited with one withdrawn consent and six excluded. Ninety-six underwent laparoscopic appendicectomy and 76 had laparoscopic cholecystectomy. Ninety-six attended clinic review and 76 had telephone follow-up. The two groups were similar in baseline variables. Non-attendance rate was higher for clinic review cohort (24% vs 6.6%, P = 0.002). Participants who received telephone review reported higher satisfaction level (9.31 vs 8.85, P = 0.002), and most patients prefer telephone follow-up (73.1%, P < 0.0001). No difference was detected for missed complications (P = 0.354). Telephone follow-up post laparoscopic appendicectomy or cholecystectomy is safe, satisfying and effective.
Publisher: Oxford University Press (OUP)
Date: 12-10-2007
DOI: 10.1634/STEMCELLS.2006-0421
Abstract: The identification and characterization of esophageal stem cells are critical to our understanding of the biology of the esophageal epithelium in health and disease. However, the proliferative compartment within the mouse esophageal epithelium remains poorly characterized. Here, we report that the basal cells of the mouse esophagus can be separated into three phenotypically and functionally distinct subpopulations based on the expression of α6 integrin and transferrin receptor (CD71). Cells that express high levels of α6 integrin and low levels of CD71, termed α6briCD71dim, are a minor subpopulation of small and undifferentiated cells that are enriched for label-retaining cells and thus represent a putative esophageal stem cell population. Conversely, cells expressing high levels of both α6 integrin and CD71 (α6briCD71bri), the majority of basal esophageal cells, are enriched for actively cycling cells and therefore represent a transit- lifying population. Kinetic analyses revealed that a third cell population, which is α6 integrin-dim and CD71-bright (α6dim), is destined to leave the basal layer and differentiate.
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.22481507
Abstract: Supplementary tables and figure
Publisher: JMIR Publications Inc.
Date: 03-09-2019
Abstract: ncreased accessibility to the internet and mobile devices has seen a rapid expansion in electronic health (eHealth) behavior change interventions delivered to patients with cancer and survivors using synchronous, asynchronous, and combined delivery methods. Characterizing effective delivery methods of eHealth interventions is required to enable improved design and implementation of evidence-based health behavior change interventions. his study aims to systematically review the literature and synthesize evidence on the success of eHealth behavior change interventions in patients with cancer and survivors delivered by synchronous, asynchronous, or combined methods compared with a control group. Engagement with the intervention, behavior change, and health outcomes, including quality of life, fatigue, depression, and anxiety, were examined. search of Scopus, Ovid MEDLINE, Excerpta Medica dataBASE, Cumulative Index to Nursing and Allied Health Literature Plus, PsycINFO, Cochrane CENTRAL, and PubMed was conducted for studies published between March 2007 and March 2019. We looked for randomized controlled trials (RCTs) examining interventions delivered to adult cancer survivors via eHealth methods with a measure of health behavior change. Random-effects meta-analysis was performed to examine whether the method of eHealth delivery impacted the level of engagement, behavior change, and health outcomes. total of 24 RCTs were included predominantly examining dietary and physical activity behavior change interventions. There were 11 studies that used a synchronous approach and 11 studies that used an asynchronous approach, whereas 2 studies used a combined delivery method. Use of eHealth interventions improved exercise behavior (standardized mean difference [SMD] 0.34, 95% CI 0.21-0.48), diet behavior (SMD 0.44, 95% CI 0.18-0.70), fatigue (SMD 0.21, 95% CI −0.08 to 0.50 SMD change 0.22, 95% CI 0.09-0.35), anxiety (SMD 1.21, 95% CI: 0.36-2.07 SMD change 0.15, 95% CI −0.09 to 0.40), depression (SMD 0.15, 95% CI 0.00-0.30), and quality of life (SMD 0.12, 95% CI −0.10 to 0.34 SMD change 0.14, 95% CI 0.04-0.24). The mode of delivery did not influence the amount of dietary and physical activity behavior change observed. hysical activity and dietary behavior change eHealth interventions delivered to patients with cancer or survivors have a small to moderate impact on behavior change and a small to very small benefit to quality of life, fatigue, depression, and anxiety. There is insufficient evidence to determine whether asynchronous or synchronous delivery modes yield superior results. Three-arm RCTs comparing delivery modes with a control with robust engagement reporting are required to determine the most successful delivery method for promoting behavior change and ultimately favorable health outcomes.
Publisher: Wiley
Date: 30-12-2017
DOI: 10.1111/ANS.12937
Publisher: MDPI AG
Date: 22-03-2021
DOI: 10.3390/NU13031020
Abstract: Background: People with upper gastrointestinal cancer are at high risk for malnutrition without universal access to early nutrition interventions. Very little data exist on the attitudes and views of health professionals on providing nutrition care to this patient cohort delivered by electronic health methods. COVID-19 has fast-tracked the adoption of digital health care provision, so it is more important than ever to understand the needs of health professionals in providing health care via these modes. This study aimed to explore the perspectives of health professionals on providing nutrition care to upper gastrointestinal cancer patients by electronic methods to allow the future scaling-up of acceptable delivery methods. Methods: Semi-structured qualitative interviews were conducted face-to-face or by telephone and recorded, de-identified and transcribed. Thematic analysis was facilitated by NVivo Pro 12. Results: Interviews were conducted on 13 health professionals from a range of disciplines across several public and private health institutions. Thematic analysis revealed three main themes: (1) the ideal model, (2) barriers to the ideal model and (3) how to implement and translate the ideal model. Health professionals viewed the provision of nutrition interventions as an essential part of an upper gastrointestinal cancer patient’s treatment with synchronous, telephone-based internal health service models of nutrition care overwhelmingly seen as the most acceptable model of delivery. Mobile application-based delivery methods were deemed too challenging for the current population serviced by these clinicians. Conclusion: The use of novel technology for delivering nutrition care to people receiving treatment for upper gastrointestinal cancers was not widely accepted as the preferred method of delivery by health professionals. There is an opportunity, given the rapid uptake of digital health care delivery, to ensure that the views and attitudes of health professionals are understood and applied to develop acceptable, efficacious and sustainable technologies in our health care systems.
Publisher: American Physiological Society
Date: 15-12-2012
Abstract: The molecular mechanism underlying the development of Barrett's esophagus (BE), the precursor to esophageal adenocarcinoma, remains unknown. Our previous work implicated sonic hedgehog (Shh) signaling as a possible driver of BE and suggested that bone morphogenetic protein 4 (Bmp4) and Sox9 were downstream mediators. We have utilized a novel in vivo tissue reconstitution model to investigate the relative roles of Bmp4 and Sox9 in driving metaplasia. Epithelia reconstituted from squamous epithelial cells or empty vector-transduced cells had a stratified squamous phenotype, reminiscent of normal esophagus. Expression of Bmp4 in the stromal compartment activated signaling in the epithelium but did not alter the squamous phenotype. In contrast, expression of Sox9 in squamous epithelial cells induced formation of columnar-like epithelium with expression of the columnar differentiation marker cytokeratin 8 and the intestinal-specific glycoprotein A33. In patient tissue, A33 protein was expressed specifically in BE, but not in normal esophagus. Expression of Cdx2, another putative driver of BE, alone had no effect on reconstitution of a squamous epithelium. Furthermore, epithelium coexpressing Cdx2 and Sox9 had a phenotype similar to epithelium expressing Sox9 alone. Our results demonstrate that Sox9 is sufficient to drive columnar differentiation of squamous epithelium and expression of an intestinal differentiation marker, reminiscent of BE. These data suggest that Shh-mediated expression of Sox9 may be an important early event in the development of BE and that the potential for inhibitors of the hedgehog pathway to be used in the treatment of BE and/or esophageal adenocarcinoma could be tested in the near future.
Publisher: Informa UK Limited
Date: 14-05-2017
DOI: 10.1080/00365521.2017.1325930
Abstract: There is no current, evidence-based therapy to prevent acute erticulitis in patients with erticular disease. Metformin has been shown to have anti-inflammatory effects in a number of disease states, in both animal models and in human observational studies. The potential therapeutic efficacy of metformin in erticular disease has not been investigated. This study aims to describe the relationship between metformin use and erticular disease in patients with diabetes mellitus. This was a retrospective case-control study. It compared metformin and other hypoglycaemic medication use in diabetic patients with uncomplicated erticulosis to those with acute erticulitis. Patients were identified using hospital International Classification of Diseases 10 (ICD-10) data, and radiology, pathology and scanned medical record databases were used to confirm diagnoses and collect all information. Chi square tests were used to determine significance of difference in categorical variables, and Mann-Whitney tests were used for continuous data. There were 174 patients with uncomplicated erticulosis and 175 patients with acute erticulitis. A diagnosis of acute erticulitis was associated with a significantly lower incidence of metformin use, than a diagnosis of uncomplicated erticular disease (44% compared to 60%, respectively, p = .002). Other oral hypoglycaemic drugs and insulin were not associated with a lower incidence of erticulitis (p = .12 and p = .24, respectively). Metformin use is associated with reduced incidence of erticulitis in diabetic patients with erticular disease. The utility of metformin as a therapeutic agent to reduce the risk of erticulitis in patients with erticular disease warrants further randomised, prospective, interventional investigation.
Publisher: Elsevier BV
Date: 03-2009
Publisher: Elsevier BV
Date: 04-2009
DOI: 10.1016/J.AMJSURG.2008.04.021
Abstract: Although proctocolectomy and ileal pouch surgery is a routine part of modern-day management for complicated ulcerative colitis, these patients are often debilitated and require close and attentive management in the early postoperative period. Here we present a rare but clinically important postoperative complication.
Publisher: Oxford University Press (OUP)
Date: 15-06-2016
DOI: 10.1002/BJS.10207
Abstract: Various minimally invasive approaches exist for the management of choledocholithiasis at the time of laparoscopic cholecystectomy. The aim of this study was to compare endoscopic retrograde cholangiopancreatography (ERCP) with laparoscopic bile duct exploration (LBDE) and test the hypothesis that intraoperative ERCP is no different to LBDE in terms of rate of bile duct clearance or retained stones. Eligible patients with choledocholithiasis undergoing emergency laparoscopic cholecystectomy were randomized to intraoperative ERCP or LBDE in a 1 : 1 ratio. The primary outcomes were rates of bile duct clearance and retained stones. Secondary outcomes were postprocedure complication rate, mortality rate, postoperative length of hospital stay, conversion to open surgery rate, procedural time and total duration of surgery. Some 104 patients were randomized, and 52 patients in each group were included in an intention-to-treat analysis. Duct clearance rates were 87 per cent for patients who had intraoperative ERCP and 69 per cent for those in the LBDE group (P = 0·057). The rate of retained stones was lower in the ERCP group than in the LBDE group: 15 versus 42 per cent respectively (P = 0·004). Median postoperative length of stay was shorter with ERCP (2 days versus 3 days for LBDE P = 0·015). Intraoperative ERCP is more effective than LBDE in terms of minimizing the rate of retained stones in patients with choledocholithiasis undergoing emergency laparoscopic cholecystectomy. Registration number: ACTRN12613000761763 (www.anzctr.org.au/).
Publisher: Elsevier BV
Date: 02-2022
Publisher: BMJ
Date: 09-2019
DOI: 10.1136/BMJOPEN-2019-031434
Abstract: The Upper Gastrointestinal Cancer Registry (UGICR) was developed to monitor and improve the quality of care provided to patients with upper gastrointestinal cancers in Australia. It supports four cancer modules: pancreatic, oesophagogastric, biliary and primary liver cancer. The pancreatic cancer (PC) module was the first module to be implemented, with others being established in a staged approach. In iduals are recruited to the registry if they are aged 18 years or older, have received care for their cancer at a participating public rivate hospital or private clinic in Australia and do not opt out of participation. The UGICR is governed by a multidisciplinary steering committee that provides clinical governance and oversees clinical working parties. The role of the working parties is to develop quality indicators based on best practice for each registry module, develop the minimum datasets and provide guidance in analysing and reporting of results. Data are captured from existing data sources (population-based cancer incidence registries, pathology databases and hospital-coded data) and manually from clinical records. Data collectors directly enter information into a secure web-based Research Electronic Data Capture (REDCap) data collection platform. The PC module began with a pilot phase, and subsequently, we used a formal modified Delphi consensus process to establish a core set of quality indicators for PC. The second module developed was the oesophagogastric cancer (OGC) module. Results of the 1 year pilot phases for PC and OGC modules are included in this cohort profile. The UGICR will provide regular reports of risk-adjusted, benchmarked performance on a range of quality indicators that will highlight variations in care and clinical outcomes at a health service level. The registry has also been developed with the view to collect patient-reported outcomes (PROs), which will further add to our understanding of the care of patients with these cancers.
Publisher: Elsevier BV
Date: 2012
DOI: 10.1016/J.EJSO.2011.08.134
Abstract: Survival rates after surgery and adjuvant chemotherapy for pancreatic ductal adenocarcinoma (PDA) remain low. Selected patients with portal/superior mesenteric vein (PV) involvement undergo PV resection at pancreaticoduodenectomy (PD). This study analyses outcomes for PD with/without PV resection in patients with PDA. A retrospective analysis of prospectively collected data on patients requiring PD for histologically proven adenocarcinoma between 1/1997 and 9/2009 identified 326 patients with PDA, with 51 requiring PD with PV resection. Patients were analyzed in two groups: PD + PV resection vs. PD alone. Multivariate analysis was used to identify predictive variables influencing survival and the Kaplan-Meier method to estimate patient survival. Mean age for patients with PV resection was 66.4 (range 46-80) years, 47% were male. Both groups had similar patient demographics, perioperative and tumor characteristics. Postoperative morbidity was similar for patients with and without PV resection (27.5 vs. 28.4%). 30-day mortality was significantly higher in patients with PV resection (13.7%) vs. PD alone (5.1%). Overall survival however was similar in both groups (median PD alone 14.8 months vs. 14.5 months PD + PV). Multivariate analysis identified age, tumor grading, stay on the ICU and lack of chemotherapy as independent risk factors for reduced long-term survival. In carefully selected patients, PV resection results in similar long-term survival compared to PD alone. In selected patients, PV infiltration may be considered a sign of anatomical proximity of the tumor, rather than only a sign of increased tumor aggressiveness.
Publisher: Humana Press
Date: 2012
DOI: 10.1007/978-1-61779-815-3_5
Abstract: Proliferation in mouse oesophageal epithelial cells is confined to the basal layer of the epithelium. Within this population, it is possible to discriminate different sub-populations using a combination of cell kinetic studies and functional assays. In particular, it is possible to distinguish basal epithelial cells, which are post-mitotic and destined to leave the basal layer and differentiate compared with those cells that remain in the cycling pool. Within the cycling basal population, there appears to be a hierarchy with respect to the rate of cell turnover which may reflect a hierarchy of "stemness", although it has not been possible to demonstrate functional differences between these populations using current in vivo tissue reconstitution assays. The aim of this chapter is to describe the development of a quantitative in vivo tissue reconstitution assay to assess the potency of candidate stem cell populations within the mouse oesophageal epithelium.
Publisher: Wiley
Date: 24-11-2017
DOI: 10.1111/ANS.13381
Abstract: The interventional management of necrotizing pancreatitis has evolved from early open surgery to delayed endoscopic or percutaneous intervention. However, few studies have directly compared the three treatment modalities. We aim to compare the outcomes of patients who had endoscopic, percutaneous or surgical interventions for necrotizing pancreatitis at our institution. This is a retrospective cohort study of patients who had interventions for necrotizing pancreatitis at our institution from 2005 to 2014. Primary outcome was length of stay (LOS) secondary outcomes were complication rate and number of procedures required for resolution of necrosis. Thirty patients were included. Mortality rate was 13% (four patients). Median LOS and time to intervention was 88 and 28 days, respectively. There were no significant differences in the computed tomography severity indices and 48-h C-reactive protein levels among the three groups. Initial endoscopic intervention was associated with a median LOS of 62 days compared with 101 days in the percutaneous group and 91 days in the surgical group (P = 0.04). There were higher rates of pancreatic fistulae (40%) (P = 0.012) and new onset diabetes (30%) (P = 0.046) in the surgical group. Median number of procedures was similar among the three groups. Median LOS for patients with delayed intervention (fourth to sixth week of pancreatitis) was 66 days, compared with 137 days in patients with early intervention (first to third week) and 104 days in patients with late intervention (seventh week onwards) (P ≤ 0.001). A delayed, endoscopy first approach appears to be a reasonable strategy as it is associated with decreased LOS and low complication rate.
No related grants have been discovered for Daniel Croagh.