Surgery (Western Health) - Research Publications

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    Use and outcomes from neoadjuvant chemotherapy in borderline resectable pancreatic ductal adenocarcinoma in an Australasian population
    Walpole, I ; Lee, B ; Shapiro, J ; Thomson, B ; Lipton, L ; Ananda, S ; Usatoff, V ; Mclachlan, S-A ; Knowles, B ; Fox, A ; Wong, R ; Cooray, P ; Burge, M ; Clarke, K ; Pattison, S ; Nikfarjam, M ; Tebbutt, N ; Harris, M ; Nagrial, A ; Zielinski, R ; Chee, CE ; Gibbs, P (WILEY, 2023-02-01)
    Background: Use of neoadjuvant (NA) chemotherapy is recommended when pancreatic ductal adenocarcinoma (PDAC) is borderline resectable. Method: A retrospective analysis of consecutive patients with localized PDAC between January 2016 and March 2019 within the Australasian Pancreatic Cancer Registry (PURPLE, Pancreatic cancer: Understanding Routine Practice and Lifting End results) was performed. Clinicopathological characteristics, treatment, and outcome were analyzed. Overall survival (OS) comparison was performed using log-rank model and Kaplan–Meier analysis. Results: The PURPLE database included 754 cases with localised PDAC, including 148 (20%) cases with borderline resectable pancreatic cancer (BRPC). Of the 148 BRPC patients, 44 (30%) underwent immediate surgery, 80 (54%) received NA chemotherapy, and 24 (16%) were inoperable. The median age of NA therapy patients was 63 years and FOLFIRINOX (53%) was more often used as NA therapy than gemcitabine/nab-paclitaxel (31%). Patients who received FOLFIRINOX were younger than those who received gemcitabine/nab-paclitaxel (60 years vs. 67 years, p =.01). Surgery was performed in 54% (43 of 80) of BRPC patients receiving NA chemotherapy, with 53% (16 of 30) achieving R0 resections. BRPC patients undergoing surgery had a median OS of 30 months, and 38% (9 of 24) achieved R0 resection. NA chemotherapy patients had a median OS of 20 months, improving to 24 months versus 10 months for patients receiving FOLFIRINOX compared to gemcitabine/nab-paclitaxel (Hazard Ratio (HR).3, p <.0001). Conclusions: NA chemotherapy use in BRPC is increasing in Australia. One half of patients receiving NA chemotherapy proceed to curative resection, with 53% achieving R0 resections. Patients receiving Infusional 5-flurouracil, Irinotecan and Oxaliplatin (FOLIRINOX) had increased survival than gemcitabine/nab-paclitaxel. Treatment strategies are being explored in the MASTERPLAN and DYNAMIC-Pancreas trials.
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    Ability of malnutrition screening and assessment tools to identify computed tomography defined low muscle mass in colorectal cancer surgery
    Djordjevic, A ; Deftereos, I ; Carter, VM ; Morris, S ; Shannon, R ; Kiss, N ; Yeung, JMC (WILEY, 2022-06)
    BACKGROUND: Malnutrition and low muscle mass are independently associated with poor outcomes in colorectal cancer (CRC). However, tools to identify low muscle mass are limited in the clinical setting. We investigated the ability of existing malnutrition screening and assessment tools to identify low muscle mass assessed by computed tomography (CT). Secondary aims were to determine the feasibility of CT analysis and handgrip strength (HGS). METHODS AND ANALYSIS: An exploratory study of patients who underwent curative surgery for CRC between February and September 2019. Nutrition tools used included body mass index (BMI), Malnutrition Screening Tool (MST), and Patient-Generated Subjective Global Assessment (PG-SGA). Muscle mass was determined by preoperative CT image at the third lumbar vertebral level (L3), and muscle strength was determined by HGS dynamometry. Fisher's exact and Mann-Whitney U tests were used to compare results of nutrition tools with CT muscle assessment. RESULTS: In total, 57 patients were included. MST classified 18 patients (32%) as at risk of malnutrition, and PG-SGA classified 10 patients (17%) as malnourished. Fifty-one (90%) CT scans were analysable and 21 (47%) had low muscle mass. Of those with low muscle mass, PG-SGA classified 22 patients (92%) as well nourished and MST classified 17 patients (71%) as not being at nutrition risk. No tool was able to identify CT-diagnosed low muscle mass. Inability to complete HGS was associated with malnutrition (P = .001). CONCLUSION: In this cohort, nutrition screening and assessment tools did not identify CT-diagnosed low muscle mass. Feasible tools to identify low muscle mass in the clinical setting are required.
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    Impact of the evolution in RAS mutation analysis in Australian patients with metastatic colorectal cancer
    Chong, CY ; Jalali, A ; Wong, HL ; Loft, M ; Wong, R ; Lee, M ; Gately, L ; Hong, W ; Shapiro, J ; Kosmider, S ; Tie, J ; Ananda, S ; Yeung, JM ; Ma, B ; Burge, M ; Jennens, R ; Tran, B ; Lee, B ; Lim, L ; Dean, A ; Nott, L ; Gibbs, P (WILEY, 2022-10)
    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.
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    Current colorectal cancer chemotherapy dosing limitations and novel assessments to personalize treatments
    Arafat, Y ; Loft, M ; Reid, F ; Kosmider, S ; Lee, M ; Gibbs, P ; Faragher, IG ; Yeung, JM (WILEY, 2022-11)
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    Elective surgery system strengthening: development, measurement, and validation of the surgical preparedness index across 1632 hospitals in 119 countries
    Glasbey, JC ; Abbott, TEF ; Ademuyiwa, A ; Adisa, A ; AlAmeer, E ; Alshryda, S ; Arnaud, AP ; Bankhead-Kendall, B ; Abou Chaar, MK ; Chaudhry, D ; Costas-Chavarri, A ; Cunha, MF ; Davies, JI ; Desai, A ; Elhadi, M ; Fiore, M ; Fitzgerald, JE ; Fourtounas, M ; Fowler, AJ ; Futaba, K ; Gallo, G ; Ghosh, D ; Gujjuri, RR ; Hamilton, R ; Haque, P ; Harrison, EM ; Hutchinson, P ; Hyman, G ; Isik, A ; Jayarajah, U ; Kaafarani, HMA ; Kadir, B ; Lawani, I ; Lederhuber, H ; Li, E ; Loffler, MW ; Lorena, MA ; Mann, H ; Martin, J ; Mazingi, D ; McClain, CD ; McLean, KA ; Meara, JG ; Ramos-De La Medina, A ; Mengesha, M ; Minaya, A ; Modolo, MM ; Moore, R ; Morton, D ; Nepogodiev, D ; Ntirenganya, F ; Pata, F ; Pearse, R ; Picciochi, M ; Pinkney, T ; Pockney, P ; van Ramshorst, GH ; Richards, T ; Roslani, AC ; Satoi, S ; Sayyed, R ; Shaw, R ; Simoes, JFF ; Smart, N ; Sulliva, R ; Sund, M ; Sundar, S ; Tabiri, S ; Taylor, EH ; Venn, ML ; Wickramasinghe, D ; Wright, N ; Yip, SBS ; Bhangu, A (ELSEVIER SCIENCE INC, 2022-11-05)
    BACKGROUND: The 2015 Lancet Commission on global surgery identified surgery and anaesthesia as indispensable parts of holistic health-care systems. However, COVID-19 exposed the fragility of planned surgical services around the world, which have also been neglected in pandemic recovery planning. This study aimed to develop and validate a novel index to support local elective surgical system strengthening and address growing backlogs. METHODS: First, we performed an international consultation through a four-stage consensus process to develop a multidomain index for hospital-level assessment (surgical preparedness index; SPI). Second, we measured surgical preparedness across a global network of hospitals in high-income countries (HICs), middle-income countries (MICs), and low-income countries (LICs) to explore the distribution of the SPI at national, subnational, and hospital levels. Finally, using COVID-19 as an example of an external system shock, we compared hospitals' SPI to their planned surgical volume ratio (SVR; ie, operations for which the decision for surgery was made before hospital admission), calculated as the ratio of the observed surgical volume over a 1-month assessment period between June 6 and Aug 5, 2021, against the expected surgical volume based on hospital administrative data from the same period in 2019 (ie, a pre-pandemic baseline). A linear mixed-effects regression model was used to determine the effect of increasing SPI score. FINDINGS: In the first phase, from a longlist of 103 candidate indicators, 23 were prioritised as core indicators of elective surgical system preparedness by 69 clinicians (23 [33%] women; 46 [67%] men; 41 from HICs, 22 from MICs, and six from LICs) from 32 countries. The multidomain SPI included 11 indicators on facilities and consumables, two on staffing, two on prioritisation, and eight on systems. Hospitals were scored from 23 (least prepared) to 115 points (most prepared). In the second phase, surgical preparedness was measured in 1632 hospitals by 4714 clinicians from 119 countries. 745 (45·6%) of 1632 hospitals were in MICs or LICs. The mean SPI score was 84·5 (95% CI 84·1-84·9), which varied between HIC (88·5 [89·0-88·0]), MIC (81·8 [82·5-81·1]), and LIC (66·8 [64·9-68·7]) settings. In the third phase, 1217 (74·6%) hospitals did not maintain their expected SVR during the COVID-19 pandemic, of which 625 (51·4%) were from HIC, 538 (44·2%) from MIC, and 54 (4·4%) from LIC settings. In the mixed-effects model, a 10-point increase in SPI corresponded to a 3·6% (95% CI 3·0-4·1; p<0·0001) increase in SVR. This was consistent in HIC (4·8% [4·1-5·5]; p<0·0001), MIC (2·8 [2·0-3·7]; p<0·0001), and LIC (3·8 [1·3-6·7%]; p<0·0001) settings. INTERPRETATION: The SPI contains 23 indicators that are globally applicable, relevant across different system stressors, vary at a subnational level, and are collectable by front-line teams. In the case study of COVID-19, a higher SPI was associated with an increased planned surgical volume ratio independent of country income status, COVID-19 burden, and hospital type. Hospitals should perform annual self-assessment of their surgical preparedness to identify areas that can be improved, create resilience in local surgical systems, and upscale capacity to address elective surgery backlogs. FUNDING: National Institute for Health Research (NIHR) Global Health Research Unit on Global Surgery, NIHR Academy, Association of Coloproctology of Great Britain and Ireland, Bowel Research UK, British Association of Surgical Oncology, British Gynaecological Cancer Society, and Medtronic.
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    Application of Machine Learning to Ranking Predictors of Anti-VEGF Response
    Arslan, J ; Benke, KK (MDPI, 2022-11)
    Age-related macular degeneration (AMD) is a heterogeneous disease affecting the macula of individuals and is a cause of irreversible vision loss. Patients with neovascular AMD (nAMD) are candidates for the anti-vascular endothelial growth factor (anti-VEGF) treatment, designed to regress the growth of abnormal blood vessels in the eye. Some patients fail to maintain vision despite treatment. This study aimed to develop a prediction model based on features weighted in order of importance with respect to their impact on visual acuity (VA). Evaluations included an assessment of clinical, lifestyle, and demographic factors from patients that were treated over a period of two years. The methods included mixed-effects and relative importance modelling, and models were tested against model selection criteria, diagnostic and assumption checks, and forecasting errors. The most important predictors of an anti-VEGF response were the baseline VA of the treated eye, the time (in weeks), treatment quantity, and the treated eye. The model also ranked the impact of other variables, such as intra-retinal fluid, haemorrhage, pigment epithelium detachment, treatment drug, baseline VA of the untreated eye, and various lifestyle and demographic factors. The results identified variables that could be targeted for further investigation in support of personalised treatments based on patient data.
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    Perineal necrotizing soft tissue infection secondary to rectal perforation from a large fish bone -a painful lesion not to be missed.
    Satheakeerthy, S ; Tang, H ; Arafat, Y ; Udayasiri, D ; Yeung, JM (Elsevier BV, 2023-05)
    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.
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    Comparison of CT derived body composition at the thoracic T4 and T12 with lumbar L3 vertebral levels and their utility in patients with rectal cancer
    Arayne, AA ; Gartrell, R ; Qiao, J ; Baird, PN ; Yeung, JMC (BMC, 2023-01-16)
    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 cm2 for T4 CSA vs 76.00 cm2 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.
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    Health service nutrition practices and associations with clinical outcomes in patients undergoing resection for upper gastrointestinal cancer: Results from the multi-centre NOURISH point prevalence study
    Deftereos, I ; Yeung, JMC ; Arslan, J ; Carter, VM ; Isenring, E ; Kiss, N (WILEY, 2023-04)
    BACKGROUND: The present study aimed to investigate health service nutrition practices of sites providing care to patients undergoing surgery for upper gastrointestinal cancer within Australia, including the provision of perioperative nutrition support services and outpatient clinics, as well as the use of evidence-based nutrition care pathways/protocols. Secondary aims were to investigate associations between the use of a nutrition care pathway/protocol and patient outcomes. METHODS: Principal investigator dietitians for the sites (n = 27) participating in the NOURISH point prevalence study participated in a purpose-built site-specific survey regarding perioperative nutrition practices and protocols. Data from the 200 patients who participated in the study (including malnutrition prevalence, preoperative weight loss and receipt of dietetics intervention, intraoperative feeding tube insertions, provision of nutrition support day 1 post surgery, length of stay, and complications) were investigated using multivariate analysis to determine associations with the sites' use of a nutrition care pathway/protocol. RESULTS: The majority of sites (>92%) reported having dietetics services available in chemotherapy/radiotherapy. Eighty-five percent of sites reported having some form of outpatient clinic service; however, a routine service was only available at 26% of sites preoperatively and 37% postoperatively. Most preoperative services were embedded into surgical/oncology clinics (70%); however, this was reported for only 44% of postoperative clinics. Only 44% had a nutrition care pathway/protocol in place. The use of a nutrition care pathway/protocol was associated with lower rates of malnutrition, as well as higher rates of preoperative dietetics intervention, intraoperative feeding tube insertions, and European Society of Clinical Nutrition and Metabolism (ESPEN) guideline compliant care day 1 post surgery. CONCLUSIONS: The results of the present study demonstrate varied perioperative outpatient nutrition services in this high-risk patient group. The use of nutrition care pathways and protocols was associated with improved patient outcomes.
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    Reversal of Hartmann's procedure: timelines, preoperative investigations and early outcomes. A single Australian institution's ten-year experience
    Suthakaran, R ; Faragher, IG ; Yeung, JMC (WILEY, 2023-01)
    BACKGROUND: Real-world data on outcomes following Hartmann's reversal is necessary to help optimize the patient experience. We have explored the timing between the index operation and its reversal; what investigations were carried out prior to this, and the associated short-term outcomes. METHODS: A retrospective study of all patients who underwent Hartmann's reversal from 2010 to 2020 within a tertiary referral centre in Melbourne, Australia. One hundred from a total of 406 (25%) who underwent an emergency Hartmann's procedure had a subsequent reversal. Complete patient data was available for 83 of these patients. RESULTS: The average patient age was 60 years, and the median time for reversal was 14.0 (IQR 10-23) months. Seventy-nine of 83 (95%) reversals had a preoperative endoscopic evaluation of both their rectal stump and a complete colonoscopy. Stoma stenosis (n = 2), patient refusal (n = 1) and emergency reversal (n = 1) were cited reasons for not undergoing preoperative endoscopic evaluation. A third (n = 28, 34%) had a computed tomography prior to reversal; the majority was due to their underlying cancer surveillance (n = 21, 75%). Reversal was associated with a morbidity rate of 47% (n = 39). Surgical site infections (SSIs) (n = 21, 25%) were the most common type of complications encountered, with the majority being superficial (n = 15, 71%). SSIs were associated with steroid use (5/21 versus 4/62, p = 0.03) and greater hospital length of stay (6 versus 10 days, p = 0.03). CONCLUSION: Only a quarter of emergency Hartmann's procedures within our institution were reversed. A significant proportion developed postoperative complications. Surgical site infection was the most common morbidity.