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Background: Traditional randomised controlled trials (RCTs) are the gold standard for evaluating the effectiveness of interventions in clinical research. Traditional RCTs however are complex, expensive and have low external validity. Registry-based randomised controlled trials (RRCTs) are an emerging alternative approach that integrates the internal validity of a traditional RCT with the external validity of a clinical registry by recruiting more real-world patients and leveraging an existing registry platform for data collection. As RRCTs are a novel research design, there is limited understanding of the RRCT landscape in Australia. This qualitative study aims to explore the RRCT landscape in Australia including current capacity and capabilities, and to identify challenges and opportunities for conducting RRCTs., Methods: We conducted 30 semi-structured interviews with 18 clinician researchers, 6 research program managers and 6 research governance officers. Interviews were audio-recorded and transcribed verbatim. We analysed the data using thematic analysis., Results: We identified four overarching themes: (1) understanding of the RRCT methodology concept and knowledge of Australian clinical registries and RRCT landscape; (2) enablers and barriers in the uptake and conduct of RRCTs; (3) ethics and governance requirements impacting the conduct of RRCTs and (4) recommendations for the promotion, support and implementation of RRCTs. Understanding of and ability to define an RRCT varied considerably amongst participants, as did their appreciation of the role the registry should play in supporting these trials. Lack of ongoing funding to support both registries and RRCTs, along with low awareness and minimal education around this methodology, were identified as the predominant barriers to the uptake of RRCTs in Australia. The simplicity of RRCTs, specifically their pragmatic nature and lower costs, was identified as one of their best attributes. There was consensus that inadequate funding, onerous research governance requirements and poor awareness of this methodology were currently prohibitive in enticing clinicians and researchers to conduct RRCTs. Recommendations to improve the uptake of RRCTs included establishing a sustainable funding model for both registries and RRCTs, harmonising governance requirements across jurisdictions and increasing awareness of RRCTs through education initiatives., Conclusions: RRCTs in Australia are an evolving methodology with slow but steady uptake across a number of clinical disciplines. Whilst RRCTs are increasingly identified as a beneficial alternative methodology to evaluate and improve current standards of care, several barriers to effective RRCT implementation were identified. Creating greater awareness of the benefits of RRCTs across a number of stakeholders to help secure ongoing funding and addressing both registry and RRCT governance challenges are two essential steps in enhancing the uptake of RRCTs in Australia and internationally., Competing Interests: Declarations. Ethics approval and consent to participate: Ethical approval was granted by the University of Melbourne Human Research Ethics Committee. Consent for publication: Written informed consent, including the publication of anonymised quotes, was obtained from all participants prior to data collection. Competing interests: The authors declare that they have no competing interests., (© 2024. The Author(s).)

Introduction: Patient body composition (BC) has been shown to help predict clinical outcomes in rectal cancer patients. Artificial intelligence algorithms have allowed for easier acquisition of BC measurements, creating a comprehensive BC profile in patients using data from an entire three-dimensional (3D) region of the body. This study has utilized AI technology to measure BC from the entire lumbosacral (L1-S5) region and assessed the associations between BC and clinical outcomes in rectal cancer patients who have undergone neoadjuvant therapy followed by surgery., Methods: A retrospective, cross sectional analysis was performed on locally advanced rectal cancer (LARC) patients treated with neoadjuvant long-course chemoradiotherapy followed by curative resection with total mesorectal excision at a tertiary referral centre, Western Health, Melbourne, Australia. A pre-trained and validated in-house AI segmentation model was used to automatically segment and measure intramuscular adipose tissue (IMAT), visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT) and skeletal muscle (SM) from CT slices across the entire L1-S5 level of each patient. Multivariate analysis between patient BC and clinical outcomes was performed., Results: Two hundred and fourteen patients were included in the study. One hundred and fifty-one (70.6%) patients were male and 63 (29.4%) patients were female. The average age at diagnosis was 62.4 (±12.7) years. SM density, but not volume, was associated with better overall survival (OS) (HR 0.24, P = 0.029), recurrence-free survival (RFS) (HR 0.45, P = 0.048) and decreased length of stay (LoS) (HR 1.58, P = 0.036). Both IMAT volume (HR 0.13, P = 0.008) and density (HR 0.26, P = 0.006) were associated with better OS., Conclusion: This study measured 3D BC from the entire lumbosacral region of rectal cancer patients. SM density was the most significant BC parameter, and was associated with improved OS, RFS and LoS. This adds to growing evidence that SM is a key component of BC in cancer patients and should be optimized prior to treatment. IMAT was also a prognostic factor, giving rise to avenues of future research into the role of adiposity on nutrition and tumour immunology., (© 2024 Royal Australasian College of Surgeons.)

Background: Surgery improves long-term survival for resectable, liver-only metastatic colorectal cancer (mCRC). With no consensus definition of "resectable" disease, decisions regarding resectability are reliant on the expertise and judgement of the treating clinician working in consultation with a multidisciplinary team (MDT). This study examines the clinical outcome versus initial assessment of resectability in an Australian population with mCRC., Patients and Methods: Patients with liver-only mCRC diagnosed January 2009 to December 2022 were identified from the Treatment of Recurrent and Advanced Colorectal Cancer (TRACC) registry. Patients were classified based on prospectively documented treatment assessment as "resectable," "potentially resectable," or "unresectable." The correlation between initial assessment of resectability and clinical outcome, and any impact of clinicopathologic factors were examined. Kaplan-Meier analysis assessed overall survival based on initial resectability assessment and resection status., Results: Of 4437 patients with mCRC identified through TRACC, 1250 (28%) had liver-only disease at presentation, with 497 (43%), 277 (24%), and 374 (33%) classified as "unresectable," "potentially resectable," and "resectable," respectively. In total, 516 (41%) ultimately underwent surgical resection, including 30 (6%) of the "initially unresectable," 148 (53%) of the "potentially resectable," and 338 (90%) of the "resectable" at a median of 9.5, 5.9, and 2.4 months from the diagnosis of liver metastases, respectively. Resection in the "unresectable" patient population was associated with younger age (mean age 63 vs. 69, P = .0006), better performance status (ECOG 0-1 100% vs. 74%, P = .0017), and fewer comorbidities (Charlson index 0-3 in 73% vs. 53%, P = .0296) compared with no resection. Median overall survival was longer for resected versus nonresected patients across all categories: "unresectable" (59.2 vs. 17.6 months, P < .0001), "potentially resectable" (57.2 vs. 22.8 months, P < .0001), and "resectable" (108 vs. 55 months, P < .0001)., Conclusions: This real-world study demonstrates the potential for "initially unresectable" patients to become surgical candidates following systemic therapy, more likely in younger and fitter patients, with overall excellent survival outcomes in resected patients. This highlights the value of routine, repeated MDT assessments for patients with liver-only disease who are continuing to respond to systemic therapy, even for those initially considered never to be surgical candidates., Competing Interests: Disclosure None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Abnormal results in common blood tests may occur several months before lung cancer (LC) and colorectal cancer (CRC) diagnosis. Identifying early blood markers of cancer and distinct blood test signatures could support earlier diagnosis in general practice., Methods: Using linked Australian primary care and hospital cancer registry data, we conducted a cohort study of 855 LC and 399 CRC patients diagnosed between 2001 and 2021. Requests and results from general practice blood tests (six acute phase reactants [APR] and six red blood cell indices [RBCI]) were examined in the 2 years before cancer diagnosis. Poisson regression models were used to estimate monthly incidence rates and examine pre-diagnostic trends in blood test use and abnormal results prior to cancer diagnosis, comparing patterns in LC and CRC patients., Results: General practice blood test requests increase from 7 months before CRC and 6 months before LC diagnosis. Abnormalities in many APR and RBCI tests increase several months before cancer diagnosis, often occur prior to or in the absence of anaemia (in 51% of CRC and 81% of LC patients with abnormalities), and are different in LC and CRC patients., Conclusions: This study demonstrates an increase in diagnostic activity in Australian general practice several months before LC and CRC diagnosis, indicating potential opportunities for earlier diagnosis. It identifies blood test abnormalities and distinct signatures that are early markers of LC and CRC. If combined with other pre-diagnostic information, these blood tests have potential to support GPs in prioritising patients for cancer investigation of different sites to expedite diagnosis., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Background: The treatment of locally advanced rectal cancer (LARC) is moving towards total neoadjuvant therapy and potential organ preservation. Of particular interest are predictors of pathological complete response (pCR) that can guide personalized treatment. There are currently no clinical biomarkers which can accurately predict neoadjuvant therapy (NAT) response but body composition (BC) measures present as an emerging contender. The primary aim of the study was to determine if artificial intelligence (AI) derived body composition variables can predict pCR in patients with LARC., Methods: LARC patients who underwent NAT followed by surgery from 2012 to 2023 were identified from the Australian Comprehensive Cancer Outcomes and Research Database registry (ACCORD). A validated in-house pre-trained 3D AI model was used to measure body composition via computed tomography images of the entire Lumbar-3 vertebral level to produce a volumetric measurement of visceral fat (VF), subcutaneous fat (SCF) and skeletal muscle (SM). Multivariate analysis between patient body composition and histological outcomes was performed., Results: Of 214 LARC patients treated with NAT, 22.4% of patients achieved pCR. SM volume (P = 0.015) and age (P = 0.03) were positively associated with pCR in both male and female patients. SCF volume was associated with decreased likelihood of pCR (P = 0.059)., Conclusion: This is the first study in the literature utilizing AI-measured 3D Body composition in LARC patients to assess their impact on pathological response. SM volume and age were positive predictors of pCR disease in both male and female patients following NAT for LARC. Future studies investigating the impact of body composition on clinical outcomes and patients on other neoadjuvant regimens such as TNT are potential avenues for further research., (© 2024 The Authors. ANZ Journal of Surgery published by John Wiley & Sons Australia, Ltd on behalf of Royal Australasian College of Surgeons.)

Background: A substantial proportion of patients with stage III colorectal cancer (CRC) are older than 70 years. Optimal adjuvant chemotherapy (AC) for older patients (OP) continues to be debated, with subgroup analyses of randomized trials not demonstrating a survival benefit from the addition of oxaliplatin to a fluoropyrimidine backbone., Patients and Methods: We analyzed the multisite Australian ACCORD registry, which prospectively collects patient, tumor and treatment data along with long term clinical follow-up. We compared OP (≥70) with stage III CRC to younger patients ([YP] <70), including the proportion recommended AC and any reasons for not prescribing AC. AC administration, regimen choice, completion rates, and survival outcomes were also examined., Results: One thousand five hundred twelve patients enrolled in the ACCORD registry from 2005 to 2018 were included. Median follow-up was 57.0 months. Compared to the 827 YP, the 685 OP were less likely to be offered AC (71.5% vs. 96.5%, P < .0001) and when offered, were more likely to decline treatment (15.1% vs. 2.8%, P < .0001). Ultimately, 60.0% of OP and 93.7% of YP received AC (P < .0001). OP were less likely to receive oxaliplatin (27.5% vs. 84.7%, P < .0001) and to complete AC (75.9% vs. 85.7%, P < .0001). The probability of remaining recurrence-free was significantly higher in OP who received AC compared to those not treated (HR 0.73, P = .04) but not significantly improved with the addition of oxaliplatin (HR 0.75, P = .18)., Conclusion: OP were less likely than YP to receive AC. Receipt of AC reduced recurrences in OP, supporting its use, although no significant benefit was observed from the addition of oxaliplatin., Competing Interests: Disclosure Oliver Piercey: OP has received travel expenses from MSD and an educational speaker fee from BMS; Valerie Heong: VH has received consulting fees or honoraria from AstraZeneca, Novartis, MSD, DKSH and receives grant funding from an NTF HIP grant and an LKC-NHG grant; Jeanne Tie: JT has received consulting fees or honoraria from Haystack Oncology, Seres Therapeutics, Amgen, Servier, Beigene, Novartis, Astra Zeneca, Merck Serono, MSD, Pierre Fabre, BMS, Daichii Sankyo, Illumina, Takeda and Gilead. All other authors report no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: There is mounting evidence that suggests sarcopenia can be used to predict survival outcomes in patients with colon cancer. However, the effect on locally advanced rectal cancer (LARC) is less clear. We sought to determine the association between sarcopenia on Overall Survival and Recurrence-free Survival (OS and RFS) in patients with LARC undergoing multimodal treatment., Methods: A retrospective study was undertaken of all pre-treatment stage 2-3 rectal cancer patients who underwent neo-adjuvant treatment and surgery with curative intent between January 2010 and September 2016 at Western Health. Sarcopenia was measured on pre-treatment staging scans at the third lumbar vertebrae and defined using cohort-derived, sex-specific thresholds. Primary outcomes were OS and RFS., Results: A total of 132 patients with LARC were analysed. Sarcopenia: Hazard ratio (HR) 3.71; 95% CI, 1.28-10.75, P = 0.016 was independently associated with worse Overall Survival following multivariate analysis. There was no significant relationship between sarcopenia and RFS: Time ratio (TR) 1.67; 95% CI 0.52-5.34, P = 0.386., Conclusion: Sarcopenia was found to be an independent risk factor for worse overall survival, but not recurrence free survival, in patients with locally advanced rectal cancer undergoing neo-adjuvant chemo-radiotherapy and surgery with curative intent., (© 2023 Royal Australasian College of Surgeons.)

The clinical presentation of gastrointestinal histoplasmosis (GIH) is often non-specific, mimicking several other gastrointestinal diseases, making diagnosis difficult. We present a case of GIH, causing bowel obstruction in an immunocompetent patient. A woman in her 80s presented with anorexia and a distended abdomen. A CT scan of the abdomen and pelvis (CTAP) showed ileal thickening. Endoscopy was performed and ileal biopsies were taken. A diagnosis of histoplasmosis was made by histopathology, and she began treatment with liposomal amphotericin and itraconazole. Despite presenting well at her routine follow-up appointments, she presented 4 months after diagnosis with worsening symptoms of anorexia and abdominal distention. CTAP showed the ileal stricture causing bowel obstruction. She underwent itraconazole and steroid treatment while having nasogastric tube decompression. Subsequent gastrografin follow through showing partial obstruction and surgical resection was planned. Unfortunately, her condition deteriorated, her kidney function worsened and she suffered from aspiration pneumonia with eventual demise., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Pelvic floor disorders, including pelvic organ prolapse (POP) and stress urinary incontinence (SUI), are serious and very common. Surgery is commonly undertaken to restore the strength of the vaginal wall using transvaginal surgical mesh (TVM). However, up to 15% of TVM implants result in long-term complications, including pain, recurrent symptoms, and infection.Clinical Relevance- In this study, a new bioengineered TVM has been developed to address these issues. The TVM is visible using noninvasive imaging techniques such as computed tomography (CT); it has a highly similar structural profile to human tissue and potential to reduce pain and inflammation. These combined technological advances have the potential to revolutionize women's health.

Background: Colorectal cancer poses a major burden. Its incidence increases with age and older patients with comorbidities have a higher likelihood of major complications. This study investigated the impact of age on health outcomes in colorectal cancer patients treated by surgery., Methods: A prospective database of all patients undergoing colorectal cancer surgery with curative intent between 2012 and 2017 was used to identify patients. A retrospective review of existing medical records investigating health-related outcomes in colorectal cancer patients undergoing surgery was performed. Primary outcomes measured were overall survival (OS) and disease-free survival (DFS). Difference in restricted mean survival times (RMST) up to a pre-specified time point of 24 months was used to compare four age groups., Results: Six-hundred and fifty-one patients were divided into four age group categories: ≤65-years (n = 244), 66 to 75-years (n = 213), 76 to 85-years (n = 162) and >85-years (n = 32). Older patients were found to have a higher rate of post-operative medical complications (including confusion) (P = 0.001) and a longer length of stay (LOS) (P = 0.01). There was no difference between the 76 to 85-year age group and >85-year age group in OS and DFS. However, there was a reduced OS in older patients (>65) compared to their younger cohorts (<65) (P = 0.04)., Conclusion: Older patients who undergo curative surgery have reduced OS, increased LOS and higher complication rates. Complex older patients may benefit from geriatric assessment and management in the peri-operative period., (© 2022 The Authors. ANZ Journal of Surgery published by John Wiley & Sons Australia, Ltd on behalf of Royal Australasian College of Surgeons.)

Necrotizing soft tissue infection caused by a large 70 mm fish bone that led to a single perforation of the rectum is an incredibly rare phenomenon. We report a case of an adult male in his 50s who presented with perianal pain. A prompt computed tomography (CT) scan revealed a foreign body had perforated through the rectum into the retrorectal space with associated gas locules, indicating a necrotizing infection. In addition, our case report explores the principles of wide exploration and debridement, the role of a defunctioning colostomy in perineal wound management, and principles of wound closure in the context of a foreign body causing significant perineal sepsis., (© 2023 The Authors.)

Background: Computed tomography (CT) derived body composition measurements of sarcopenia are an emerging form of prognostication in many disease processes. Although the L3 vertebral level is commonly used to measure skeletal muscle mass, other studies have suggested the utilisation of other segments. This study was performed to assess the variation and reproducibility of skeletal muscle mass at vertebral levels T4, T12 and L3 in pre-operative rectal cancer patients. If thoracic measurements were equivalent to those at L3, it will allow for body composition comparisons in a larger range of cancers where lumbar CT images are not routinely measured., Research Methods: Patients with stage I - III rectal cancer, undergoing curative resection from 2010 - 2014, were assessed. CT based quantification of skeletal muscle was used to determine skeletal muscle cross sectional area (CSA) and skeletal muscle index (SMI). Systematic differences between the measurements at L3 with T4 and T12 vertebral levels were evaluated by percentile rank differences to assess distribution of differences and ordinary least product regression (OLP) to detect and distinguish fixed and proportional bias., Results: Eighty eligible adult patients were included. Distribution of differences between T12 SMI and L3 SMI were more marked than differences between T4 SMI and L3 SMI. There was no fix or proportional bias with T4 SMI, but proportional bias was detected with T12 SMI measurements. T4 CSA duplicate measurements had higher test-retest reliability: coefficient of repeatability was 34.10 cm 2 for T4 CSA vs 76.00 cm 2 for T12 CSA. Annotation time (minutes) with L3 as reference, the median difference was 0.85 for T4 measurements and -0.03 for T12 measurements. Thirty-seven patients (46%) had evidence of sarcopenia at the L3 vertebral level, with males exhibiting higher rates of sarcopenia. However, there was no association between sarcopenia and post-operative complications, recurrence or hospital LOS (length of stay) in patients undergoing curative resection., Conclusions: Quantifying skeletal muscle mass at the T4 vertebral level is comparable to measures achieved at L3 in patients with rectal cancer, notwithstanding annotation time for T4 measurements are longer., (© 2023. The Author(s).)

Background: RAS mutation testing now routinely informs the optimal management of metastatic colorectal cancer (mCRC), specifically the finding of a RAS mutation defines patients who will not benefit from treatment with an epidermal growth factor receptor inhibitor. Over time more RAS genes have been tested and more sensitive techniques used., Aims: To review routine care RAS testing and results over time., Methods: A retrospective analysis of the molecular data collected prospectively in the multi-site Treatment of Recurrent and Advanced Colorectal Cancer (TRACC) registry from 2009 to 2018 was undertaken. Patients with RAS data were further analyzed. In parallel, the RAS mutation status of patients enrolled in the Test Tailor Treat (TTT) program was examined for 2011-2018., Results: Of 2908 patients in the TRACC registry, 1892 (65%) were tested, with 898 (47%) of tested patients found to be RAS mutant (RASmt). RAS data were available for 5935 TTT patients. Of the tested TRACC patients diagnosed in 2009 and 2010, 38% were RASmt. For each 2-year period from 2011/2012 through to 2017/2018, the prevalence of RASmt in TRACC and TTT was 42% and 40% (2011/2012), 52% and 40% (2013/2014), 47% and 49% (2015/2016), and 47% and 49% (2017/2018)., Conclusions: Based on both TRACC and TTT data, the proportion of patients reported to have a RAS mutation increased from 2009 to 2015 but has remained relatively stable in recent years. The increased proportion of RASmt patients observed over time is likely largely driven by the uptake of extended RAS testing., (© 2022 John Wiley & Sons Australia, Ltd.)

For patients with refractory metastatic colorectal cancer (mCRC) treatment with Trifluridine/Tipiracil, also known as TAS-102, improves overall survival. This study aims to investigate the efficacy and safety of TAS-102 in a real-world population from Victoria, Australia. A retrospective analysis of prospectively collected data from the Treatment of Recurrent and Advanced Colorectal Cancer (TRACC) registry was undertaken. The characteristics and outcomes of patients receiving TAS-102 were assessed and compared to those enrolled in the registration study (RECOURSE). Across 13 sites, 107 patients were treated with TAS-102. The median age was 60 years (range: 31-83), compared to 63 for RECOURSE. Comparing registry TAS-102-treated and RECOURSE patients, 75% vs 100% were ECOG performance status 0-1, 74% vs 79% had initiated treatment more than 18 months from diagnosis of metastatic disease and 36% vs 49% were RAS wild-type. Median time on treatment was 10.4 weeks (range: 1.7-32). Median progression-free survival (PFS) was 3.3 months compared to 2 months in RECOURSE, while median overall survival was the same at 7.1 months. Two patients (2.3%) had febrile neutropenia and there were no treatment-related deaths, where TAS-102 dose at treatment initiation was at clinician discretion.TRACC registry patients treated with TAS-102 were younger than those from the RECOURSE trial, with similar overall survival observed. Less strict application of RECIST criteria and less frequent imaging may have contributed to an apparently longer PFS., (Copyright © 2021. Published by Elsevier Inc.)

Background: Implementation studies of complex interventions such as nutrition care pathways are important to health services research, as they support translation of research into practice. There is limited research regarding implementation of a nutrition care pathway in an upper gastrointestinal (UGI) cancer population. The aim of this study was to comprehensively evaluate the implementation process of a perioperative nutrition care pathway in UGI cancer surgery using The Consolidated Framework for Implementation Research (CFIR)., Methods: This was a mixed methods implementation study conducted during a pilot study of a standardised nutrition care pathway across four major hospitals between September 2018 to August 2019. Outcome measures included five focus groups among study dietitians (n = 4-8 per group), and quantitative satisfaction surveys from multi-disciplinary team (MDT) members (n = 14) and patients (n = 18). Focus group responses were analysed thematically using the CFIR constructs, which were used as a priori codes. Survey responses were summarised using means and standard deviations. A convergent parallel mixed methods approach according to CFIR domains and constructs was used to integrate qualitative and quantitative data., Results: Qualitative data demonstrated that dietitian perceptions primarily aligned with five CFIR constructs (networks and communications, structural characteristics, adaptability, compatibility and patient needs/resources), indicating a complex clinical and implementation environment. Challenges to implementation mostly related to adapting the pathway, and the compatibility of nutrition coordination to existing aspects of care within each setting. Identified benefits from dietitian qualitative data and MDT survey responses included increased engagement between the dietitian and MDT, and a more proactive approach to nutrition care. Patients were highly satisfied with the service, with the majority of survey items being rated highly (≥4 of a possible 5 points)., Conclusions: The nutrition care pathway was perceived to be beneficial by key stakeholders. Based on the findings, sustainability and compliance to this model of care may be achieved with improved systems level coordination and communication., (© 2022. The Author(s).)

Background: Postoperative nutrition support is an essential component of management in upper gastrointestinal (UGI) cancer resection, however there is limited knowledge of current clinical practice. This study aimed to describe the postoperative nutrition support received by patients undergoing UGI cancer resections, assess adherence with ESPEN surgical guideline recommendations, and to investigate differences between oesophageal, gastric and pancreatic surgeries. The secondary aim was to explore the association of adherence with ESPEN guidelines and provision of nutrition support, with surgical complications and length of stay (LOS)., Methods: The NOURISH point prevalence study was conducted between September 2019-June 2020 across 27 Australian tertiary centres. Malnutrition was diagnosed using subjective global assessment. Data on postoperative diet codes, prescription of nutrition support (oral (ONS), enteral (EN), parenteral (PN)) and nutritional adequacy were collected by dietitians for the first 10 days of admission. Fisher's exact test was used to determine differences in nutritional management and adherence to ESPEN guidelines between surgery types. Multivariate regression analysed associations with surgical outcomes., Results: Two-hundred participants were included (42% pancreatic, 33% oesophageal, 25% gastric surgery). Overall, only 34.9% (n = 53) met the guideline recommendations that were applicable to them. Early oral intake of fluids or solids (within 24 h post surgery) was initiated for 23.5% (n = 47), whilst ONS/EN/PN was initiated for 49.5% (n = 99). Only 25% of pancreatic surgeries had nutrition support initiated on the first postoperative day compared to 86.4% of oesophageal and 42.0% of gastric surgeries (p < 0.001). In those who were 'nil by mouth', EN/PN were commenced within 24 h for 51.0% (n = 78), with 18.5% and 45.2% for pancreatic and gastric surgeries compared to 86.0% in oesophageal surgeries (p < 0.001). In malnourished patients, 35.7% (n = 30) commenced EN within 24 h, with 11.1% and 31.8% for pancreatic and gastric compared to 73.1% in oesophageal surgeries (p < 0.001). For patients meeting <60% energy/protein requirements for ≥7 days, only 14.8% (n = 9) received EN/PN, with 2.5% and 16.7% of pancreatic and gastric compared to 75.0% of oesophageal surgeries (p < 0.001). The number of days spent 'nil by mouth' or 'clear fluids' without EN/PN, as well as number of days with <60% estimated requirements met were independently associated with increased LOS and complications., Conclusions: Overall, there was poor adherence to the majority of assessed ESPEN guidelines, and care for patients undergoing pancreatic and gastric surgeries was less compliant than oesophagectomy. Poor nutritional adequacy was associated with increased LOS and complications. There is a clear need for knowledge translation and implementation studies to increase adherence to evidence-based recommendations in the Australian setting supported by an understanding of barriers and enablers to optimal postoperative nutrition management., Competing Interests: Declaration of competing interest ID has received a research grant from the Australian Society of Enteral and Parenteral Nutrition (AuSPEN), unrelated to this study., (Copyright © 2021 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

In this study, we built upon our previous work to demonstrate the distribution and transport of AAV5-green fluorescent protein (GFP) following a single convection-enhanced delivery infusion into the nonhuman primate cerebellum, with no untoward side effects noted. Dosing under magnetic resonance imaging guidance revealed a sixfold larger volume of distribution compared with the volume of infusion, with no evidence of reflux underscoring the convective properties of the cerebellum and step design of the cannula. Postmortem tissue analysis, 4 weeks post-adeno-associated viral (AAV) delivery, revealed the robust presence of the transgene in situ , with GFP detection in secondary regions not directly targeted by the infusion, denoting distal transport of the vector. Irrespective of tropism, a twofold larger area of transgene expression was found and was corroborated against the presence of contrast on T1-weighted images. Different levels of transduction were detected between animals, which were negatively correlated with the level of antibody titer against the GFP construct, whereby the higher the antibody titer, the lower the level of transgene expression. These findings support the use of the posterior fossa as a potential target site for direct delivery of gene-based therapeutics for cerebellar diseases.

Background: Patients undergoing surgery for upper gastrointestinal (UGI) cancer are at high risk of malnutrition, and a multidisciplinary approach to management is recommended. This study aimed to determine practices, awareness and perceptions of multi-disciplinary clinicians with regards to malnutrition screening and provision of nutrition support., Methods: A national survey of dietitians, surgeons, oncologists and nurses was conducted using a 30-item online REDCap survey, including questions regarding self-reported malnutrition screening/nutrition support practices, awareness and perceptions, and barriers and enablers. The survey was distributed via professional organisations/networks between 1st September and 30th November 2020. Results are presented as counts and percentages., Results: There were 130 participants (56% dietitians, 25% surgeons, 11% nurses, 8% oncologists). The majority reported that dietitians and nurses performed malnutrition screening, and dietitians and surgeons prescribed nutrition support. Most participants reported that their health service had dietetics support available overall (98%), however only 41% reported having an outpatient service. Participants (>90%) demonstrated very high awareness of the significance of malnutrition and the importance of early nutrition support. Participants mostly perceived dietitians, nurses and surgeons to be responsible for malnutrition screening, whilst responsibility of prescription of nutrition support was mostly dietitians and surgeons. There were a higher number of barriers for the outpatient setting (48%) than the inpatient setting (38%)., Conclusions: Participants identified a high awareness of the importance of identification and treatment of malnutrition in UGI cancer surgery. However reported practices varied and appear to be lacking in the outpatient setting, with significant barriers identified to providing optimal nutrition care., Competing Interests: Declaration of competing interest ID has received investigator-initiated research grants from the Nestle Health Sciences and the Australian Society of Enteral and Parenteral Nutrition (AuSPEN), unrelated to this study., (Copyright © 2021 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Background: Capsaicin is used in several areas of non-human primate research including allodynia and dermal blood flow (DBF). The capsaicin-induced DBF increase was measured using laser Doppler imaging (LDI), but this response is known to diminish upon repeated topical applications. Refinement of the experimental procedures could improve the rigor and reproducibility of the DBF migraine model., Methods: Optimal anatomical site in cynomolgus was determined, and conditions and experimental settings for DBF measurement using LDI were established. Then, two study design trial structures were compared., Results: Medial thigh was the preferrable site, and an ethanol-Tween 20 formulation of capsaicin was desirable. A 1-week washout for contralateral side or 2-week washout for ipsilateral side was necessary to eradicate capsaicin desensitization., Conclusions: With the established technicality in DBF measurements in cynomolgus macaques, the capsaicin-induced DBF model may be utilized in translational medical research in developing migraine therapeutics., (© 2021 John Wiley & Sons Ltd.)

Background: Preoperative nutrition intervention is recommended prior to upper gastrointestinal (UGI) cancer resection; however, there is limited understanding of interventions received in current clinical practice. This study investigated type and frequency of preoperative dietetics intervention and nutrition support received and clinical and demographic factors associated with receipt of intervention. Associations between intervention and preoperative weight loss, surgical length of stay (LOS), and complications were also investigated., Methods: The NOURISH Point Prevalence Study was conducted between September 2019 and May 2020 across 27 Australian tertiary centres. Subjective global assessment and weight were performed within 7 days of admission. Patients reported on preoperative dietetics and nutrition intervention, and surgical LOS and complications were recorded., Results: Two-hundred patients participated (59% male, mean (standard deviation) age 67 (10)). Sixty percent had seen a dietitian preoperatively, whilst 50% were receiving nutrition support (92% oral nutrition support (ONS)). Patients undergoing pancreatic surgery were less likely to receive dietetics intervention and nutrition support than oesophageal or gastric surgeries ( p < 0.001 and p = 0.029, respectively). Neoadjuvant therapy ( p = 0.003) and malnutrition ( p = 0.046) remained independently associated with receiving dietetics intervention; however, 31.3% of malnourished patients had not seen a dietitian. Patients who received ≥3 dietetics appointments had lower mean (SD) percentage weight loss at the 1-month preoperative timeframe compared with patients who received 0-2 appointments (1.2 (2.0) vs. 3.1 (3.3), p = 0.001). Patients who received ONS for >2 weeks had lower mean (SD) percentage weight loss than those who did not (1.2 (1.8) vs. 2.9 (3.4), p = 0.001). In malnourished patients, total dietetics appointments ≥3 was independently associated with reduced surgical complications (odds ratio 0.2, 95% confidence interval (CI) 0.1, 0.9, p = 0.04), and ONS >2 weeks was associated with reduced LOS (regression coefficient -7.3, 95% CI -14.3, -0.3, p = 0.04)., Conclusions: Despite recommendations, there are low rates of preoperative dietetics consultation and nutrition support in this population, which are associated with increased preoperative weight loss and risk of increased LOS and complications in malnourished patients. The results of this study provide insights into evidence-practice gaps for improvement and data to support further research regarding optimal methods of preoperative nutrition support.

Objective: We describe a pipeline for creating and publishing online schematic 3D anatomical models, that requires minimal resources and facilitates an intuitive understanding of complex surgical structures, using the inguinal canal as an example., Design: The open source 3D modeling software Blender 1 was used to generate the inguinal canal model. With screen recording enabled, the model was annotated within a 3D space and the resultant video tutorial uploaded to YouTube. The 3D model was also exported to an online web portal that students could navigate independently. Feedback was collated from YouTube and the online platform over two years via video comments and an online form for platform visitors., Setting: Department of Surgery, Western Precinct, University of Melbourne, Melbourne, Australia., Participants: A total of 5,438 students utilized the online platform over the past 24 months. Video tutorials depicting the inguinal canal model were viewed a total of 162,181 times across the same period., Results: Feedback was uniformly positive with a predominant theme of faster comprehension times that were attributed to the visuospatial feedback complementing traditional resources., Conclusions: The development of online 3D schematic models is achievable with the use of free and readily accessible computer software. These models allow students to "walk through" complex anatomical areas, which may enable them to better orientate and understand previously difficult to teach surgical concepts., (Copyright © 2021 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: Malnutrition is a significant problem in gastrointestinal (GI) cancer, and accurate screening and identification is essential to ensure appropriate nutrition intervention. This study aims to determine current evidence for concurrent validity of malnutrition screening tools in GI cancer., Methods: A systematic review was undertaken according to PRISMA guidelines, using four databases. Studies investigating the concurrent validity of malnutrition screening tools against a reference standard of Patient Generated Subjective Global Assessment (PG-SGA) or Subjective Global Assessment (SGA) in adult patients with GI cancer were identified. Screening, quality assessment using the QUADAS-2 checklist, and data extraction were performed by two independent reviewers. Concurrent validity ratings were applied using predefined criteria., Results: Six studies investigating concurrent validity of the Nutrition Risk Index (NRI), Malnutrition Universal Screening Tool (MUST), Malnutrition Screening Tool (MST) and Nutrition Risk Screening 2002 criteria (NRS-2002) were included. There was variation in concurrent validity ratings ranging from poor-good for all tools, depending on treatment type, stage and population characteristics., Conclusion: Recommendations regarding the use of one tool over another could not be made. However, in the absence of a clear recommendation specific to GI cancer, screening tools that are well validated in general clinical populations should be utilised. The MST can be recommended based on validity data against the PG-SGA and SGA from other oncology populations. If indicated, malnutrition screening should then be followed by thorough nutritional assessment., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Aim: Colorectal cancer surveillance is an essential part of care and should include clinical review and follow-up investigations. There is limited information regarding postoperative surveillance and survivorship care in the Australian context. This study investigated patterns of colorectal cancer surveillance at a large tertiary institution., Methods: A retrospective review of hospital records was conducted for all patients treated with curative surgery between January 2012 and June 2017. Provision of clinical surveillance, colonoscopy, computed tomography (CT), and carcinoembryonic antigen (CEA) within 24 months postoperatively were recorded. Kaplan-Meier estimates were used to evaluate time-to-surveillance review and associated investigations., Results: A total of 675 patients were included in the study. Median time to first postoperative clinical review was 20 days (95% confidence interval (CI), 18-21) with only 31% of patients having their first postoperative clinic review within 2 weeks. Median time to first CEA was 100 days (95% CI, 92-109), with 47% of patients having their CEA checked within the first 3 months, increasing to 68% at 6 months. Median time to first follow-up CT scan was 262 days (95% CI, 242-278) and for colonoscopy, 560 days (95% CI, 477-625). Poor uptake of surveillance testing was more prevalent in patients from older age groups, those with multiple comorbidities, and higher stage cancers., Conclusion: Colorectal cancer surveillance is multi-disciplinary and involves several parallel processes, many of which lead to inconsistent follow-up. Further prospective work is required to identify the reasons for variation in care and which aspects are most important to cancer patients., (© 2020 John Wiley & Sons Australia, Ltd.)

Objective: To describe changes in health-related quality of life (QoL) from before colorectal cancer (CRC) surgery to 1 and 3-month post-surgery in patients diagnosed pre-operatively as sarcopenic or non-sarcopenic by computed tomography (CT) analysis., Methods: Secondary analysis of a prospective observational cohort study with one pre-operative and two post-operative assessments. Patient-reported outcome measures (PROMs) were collected at each timepoint using Functional Assessment of Cancer Therapy-Colorectal and the EuroQol-5D (EQ-5D) questionnaires. Pre-operative staging CT scans of the third lumbar vertebra (axial slice) were analysed using Slice-O-Matic Software to determine if patients had CT defined sarcopenia by employing sex-specific threshold values for skeletal muscle index. Patient-reported outcome measure scores were compared with minimal clinical important difference estimates to determine if changes were clinically significant., Results: Twenty-five of 40 patients were found to be sarcopenic. The difference between sarcopenic groups on the EQ-5D was medium-sized and clinically significant, with the sarcopenic group reporting lower health status. The non-sarcopenic group displayed a clinically significant reduction in physical wellbeing post-operatively. The sarcopenic group did not demonstrate a clinically important reduction in physical wellbeing. For functional wellbeing, the sarcopenic group recorded a clinically significant reduction at the 1-month timepoint, trending back towards baseline by the 3-month timepoint. The non-sarcopenic group recorded almost no change in functional scores., Conclusion: This study explored the novel concept of the effect of sarcopenia on QoL in the CRC surgical setting. Clinically significant changes were identified at both post-operative timepoints. This highlights an important proof of concept that PROMs can detect meaningful clinical change in CRC patients in the context of sarcopenia and should be further explored.

Background: Anaemia is a common manifestation of colorectal cancer (CRC). However, appropriate workup prior to surgery and the effect of anaemia on outcomes have not been well defined. This study aimed to describe preoperative anaemia incidence, investigations performed, treatment and associated complications in a CRC surgical population at a single large tertiary institution in Australia., Methods: Patients who received surgery with curative intent for CRC between 2012 and 2017 were identified from a prospectively maintained database. Demographic and clinical outcome data were analysed., Results: In total, 754 patients with CRC were included. Anaemia was found in 350 (46.4%) patients, of which 124 (35.4%) were microcytic, 20 (5.7%) were macrocytic and 206 (58.9%) were normocytic. Older patients were more likely to have anaemia (mean age 70.28 years, standard deviation (SD) 12.98 versus 64.74 years, SD 11.74). Only 89 patients (25.4%) were tested for iron deficiency, and of these, 76 (85.4%) were found to be iron deficient and 42 (47.7%) had low ferritin. Preoperative anaemia was associated with a higher incidence of postoperative complications (adjusted odds ratio (OR) 1.46, 95%, CI 1.04-2.05; P = 0.03) and a longer length of stay (LOS; average 1.8 days; 95% CI 0.3-3.3 days)., Conclusion: A significant proportion of CRC patients had anaemia and the majority were normocytic. Only a small number of anaemic patients were tested for iron deficiency. Preoperative anaemia had an adverse effect on LOS and postoperative complications. The evaluation of anaemic patients is essential in CRC patients undergoing surgery., (© 2021 Royal Australasian College of Surgeons.)

Background: The role of lateral lymph node dissection (LLND) in the treatment of patients with low rectal cancer with enlarged lateral lymph nodes (LLN+) is under investigation. Enthusiasm for LLND stems from a perceived reduction in local recurrence (LR). We aimed to compare the LR rate for LLN+ patients with LLN- patients, treated with neoadjuvant chemoradiotherapy (nCRT) and surgery, in a hospital that does not perform LLND., Methods: A retrospective study of all patients with clinical stage 3 low rectal cancer who completed nCRT and surgery between 2008 and 2017 at Western Health was performed. Outcomes for LLN+ patients were compared with LLN- patients. The primary outcome was LR. Secondary outcomes included distant metastases, disease-free survival and overall survival., Results: There were 110 patients treated for stage 3 low rectal cancer over 10 years. There was no significant difference in the LR rate, with one LR from 28 LLN+ patients and one LR from 82 LLN- patients (4% versus 1.2%, P = 0.44). There were no significant differences in median disease-free survival (41 versus 52 months, P = 0.19) or mean overall survival (62 versus 60 months, P = 0.80). Of all patients studied, 21% developed distant metastases., Conclusion: LR after nCRT and surgery in patients with stage 3 rectal cancer is rare, irrespective of lateral pelvic node status. These data, along with the uncertain benefit and known risks of LLND, supports the continued use of standard therapy in these patients. Strategies to address distant failure in these patients should be explored., (© 2021 Royal Australasian College of Surgeons.)

Background: Currently no consensus exists regarding what pre-reversal investigations are required to assess integrity of the rectal anastomosis. The objective of this study was to compare pre-reversal assessments of anastomotic integrity and to evaluate trends that might have influenced timings for reversal., Methods: From a prospectively maintained database, patients with colorectal cancer resections between March 2012 and October 2019 were identified. Patient characteristics, pre-reversal contrast enema and flexible sigmoidoscopy findings were recorded, and management of complications were recorded. Time-to-ileostomy reversal and time series for trends were analysed., Results: There were 154 patients included. Pre-reversal contrast enema or sigmoidoscopy detected a possible stricture or leak at the rectal anastomotic site in 11% (15/132) and 15% (18/112), respectively. When both modalities were used there was concordance of 86.1% and a positive likelihood ratio of 5.73. Of 125 (81.2%) ileostomies reversed, the median time-to-reversal was 11.99 months; time series analysis over the 7-year period showed no significant trend for average patient-days from booking to reversal (P = 0.60). Cox regression modelling did not identify any influential risk factors for the times taken to reversal., Conclusion: This study supports the use of both contrast enema and flexible sigmoidoscopy in the assessment of rectal anastomosis integrity. Most patients with complications can have their ileostomies reversed. Patients who have adjuvant chemotherapy have a prolonged time to reversal., (© 2020 Royal Australasian College of Surgeons.)