ORCID Profile
0000-0002-6004-4764
Current Organisation
SA Health
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Publisher: Wiley
Date: 08-09-2023
DOI: 10.1111/ANS.18662
Publisher: MDPI AG
Date: 18-04-2023
Abstract: An overabundance of desmoplasia in the tumour microenvironment (TME) is one of the defining features that influences pancreatic ductal adenocarcinoma (PDAC) development, progression, metastasis, and treatment resistance. Desmoplasia is characterised by the recruitment and activation of fibroblasts, heightened extracellular matrix deposition (ECM) and reduced blood supply, as well as increased inflammation through an influx of inflammatory cells and cytokines, creating an intrinsically immunosuppressive TME with low immunogenic potential. Herein, we review the development of PDAC, the drivers that initiate and/or sustain the progression of the disease and the complex and interwoven nature of the cellular and acellular components that come together to make PDAC one of the most aggressive and difficult to treat cancers. We review the challenges in delivering drugs into the fortress of PDAC tumours in concentrations that are therapeutic due to the presence of a highly fibrotic and immunosuppressive TME. Taken together, we present further support for continued/renewed efforts focusing on aspects of the extremely dense and complex TME of PDAC to improve the efficacy of therapy for better patient outcomes.
Publisher: MDPI AG
Date: 10-06-2022
Abstract: Background and Aims: A concerning rise in incidence of young-onset cancers globally led to the examination of trends in incidence and survival of gastrointestinal (GI) adenocarcinomas in the Northern Territory (NT), Australia, over a 28-year period, with a special emphasis on Indigenous peoples. Methods: This cross-sectional analysis of a prospective longitudinal database, NT Cancer Registry (1990–2017), includes all reported cases of GI (oesophagus, gastric, small intestinal, pancreas, colon, and rectum) adenocarcinomas. Poisson regression was used to estimate incidence ratio ratios, and survival was modelled using Cox proportional hazard models separately for people aged 18–50 years and years. Results: A total of 1608 cases of GI adenocarcinoma were recorded during the time of the study. While the overall incidence in people 18–50 years remained unchanged over this time (p = 0.51), the rate in in iduals aged years decreased (IRR = 0.65 (95% CI 0.56–0.75 p 0.0001)). Incidence rates were significantly less in females years (IRR = 0.67 95% CI 0.59–0.75 p 0.0001), and their survival was significantly better (HR = 0.84 (95%CI 0.72–0.98 p 0.03)) compared to males. Overall survival across all GI subsites improved in both age cohorts, especially between 2010 and 2017 (HR = 0.45 (95%CI 0.29–0.72 p 0.0007) and HR = 0.64 (95%CI 0.52–0.78 p 0.0001), respectively) compared to 1990–1999, driven by an improvement in survival in colonic adenocarcinoma alone, as the survival remained unchanged in other GI subsites. The incidence was significantly lower in Indigenous patients compared to non-Indigenous patients, in both age cohorts (18–50 years IRR = 0.68 95% CI 0.51–0.91 p 0.009 and years IRR = 0.48 95% CI 0.40–0.57 p 0.0001). However, Indigenous patients had worse survival rates (18–50 years HR = 2.06 95% CI 1.36–3.11 p 0.0007 and years HR = 1.66 95% CI 1.32–2.08 p 0.0001). Conclusions: There is a trend towards an increased incidence of young-onset GI adenocarcinomas in the NT. Young Indigenous patients have lower incidence but worse survival across all GI subsites, highlighting significant health inequities in life expectancy. Targeted, culturally safe Indigenous community-focussed programs are needed for early detection and patient-centred management of GI adenocarcinomas.
Publisher: Wiley
Date: 12-10-2022
DOI: 10.1111/ANS.18072
Abstract: High‐quality colonoscopy is vital for the detection and removal of adenomatous polyps and early diagnosis of colorectal cancer. The aim of this study was to prospectively assess the quality and safety of colonoscopies performed in the non‐metropolitan setting. Key performance indicators measured include completion, polypectomy and adenoma/serrated polyp detection rates, rate of adequate bowel preparation, withdrawal time and complications. Prospective data collection for all colonoscopies performed over a one‐year period in seven non‐metropolitan South Australian hospitals. Two general surgeons and twelve registrars working in rural South Australian hospitals (Mount Gambier, Millicent, Naracoorte, Port Lincoln, Port Augusta, Whyalla and Berri) contributed to this study. In total 3497 colonoscopies were analysed. Complete colonoscopy was achieved in 96.1%. The adenoma detection and serrated polyp detection rates were 25.6% and 5.4% respectively. Cancer was detected in 71 patients (2%). Colonic perforation occurred in five patients (0.1%). There was no procedure‐related mortality. Colonoscopy performed in the non‐metropolitan Australian setting outperforms key performance indicators set by national institutions. This is the first Australian prospective multi‐centre study investigating the quality and safety of endoscopic procedures.
Publisher: Wiley
Date: 20-04-2023
DOI: 10.1111/ANS.18482
Abstract: Colorectal cancer with synchronous liver‐only metastasis is managed with a multimodal approach, however, optimal sequencing of modalities remains unclear. A retrospective review of all consecutive rectal or colon cancer cases with synchronous liver‐only metastasis was conducted from the South Australian Colorectal Cancer Registry from 2006 to 2021. This study aimed to investigate how order and type of treatment modality affects overall survival. Data of over 5000 cases were analysed ( n = 5244), 1420 cases had liver‐only metastasis. There were a greater number of colon than rectal primaries ( N = 1056 versus 364). Colonic resection was the preferred initial treatment for the colon cohort (60%). In the rectal cohort, 30% had upfront resection followed by 27% that had chemo‐radiotherapy as 1st line therapy. For the colon cohort, there was an improved 5‐year survival with surgical resection as initial treatment compared to chemotherapy (25% versus 9%, P 0.001). In the rectal cohort, chemo‐radiotherapy as the initial treatment was associated with an improved 5‐year survival compared to surgery or chemotherapy (40% versus 26% versus 19%, P = 0.0015). Patients who were able to have liver resection had improved survival, with 50% surviving over 5 years compared to 12 months in the non‐resected group ( P 0.001). Primary rectal KRAS wildtype patients who underwent liver resection and received Cetuximab had significantly worse outcomes compared to KRAS wildtype patients who did not ( P = 0.0007). Where surgery is possible, resection of liver metastasis and primary tumour improved overall survival. Further research is required on the use of targeted treatments in patients undergoing liver resection.
No related grants have been discovered for Mia Shepherdson.