Surgery (St Vincent's) - Research Publications

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    Robotic beyond total mesorectal excision surgery for primary and recurrent pelvic malignancy: Feasibility and short-term outcomes
    Tomas Larach, J ; Flynn, J ; Fernando, D ; Mohan, H ; Rajkomar, A ; Waters, PS ; Kong, J ; McCormick, JJ ; Heriot, AG ; Warrier, SK (WILEY, 2022-07)
    AIM: To explore the feasibility and safety of robotic beyond total mesorectal excision (TME) surgery for primary and recurrent pelvic malignancy. METHODS: Patients undergoing robotic beyond TME resections for primary or recurrent pelvic malignancy between July 2015 and July 2021 in a public quaternary and a private tertiary centre were included. Demographic and clinical data were recorded and outcomes analysed. RESULTS: Twenty-four patients (50% males) were included, with a median age of 58 (45-70.8) years, and a BMI of 26 (24.3-28.1) kg/m2 . Indication for surgery was rectal adenocarcinoma in nineteen, leiomyosarcoma in two, anal squamous cell carcinoma in one and combined rectal and prostatic adenocarcinoma in two patients. All patients required resection of at least one adjacent pelvic organ including genitourinary structures (n = 23), internal iliac vessels (n = 3) and/or bone (n = 2). Eleven patients had a restorative procedure. Of the 13 nonrestorative cases, nine needed perineal reconstruction with a flap. There was one conversion due to bleeding. The mean operating time was 370 (285-424) min, and the median blood loss was 400 (200-2,000) ml. The median length of stay was 16 (9.3-23.8) days. Fourteen patients (58.3%) had postoperative complications; eight of them (33.3%) were Clavien-Dindo III or more complication. Twenty-three (95.8%) patients had an R0 resection. During a median follow-up of 10 (7-23.5) months, five patients (20.8%) had systemic recurrences. No local recurrences were identified during the study period. CONCLUSION: Implementation of robotic beyond TME surgery for primary and recurrent pelvic malignancy is feasible within a highly specialised setting.
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    Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in small bowel adenocarcinoma with peritoneal metastasis: a systematic review
    Chen, V ; Jones, M ; Cohen, L ; Yang, W ; Bedi, J ; Mohan, HM ; Apte, SS ; Larach, JT ; Flood, M ; Heriot, A ; Kong, J ; Warrier, S (WALTER DE GRUYTER GMBH, 2022-12-13)
    OBJECTIVES: Small bowel adenocarcinoma (SBA) with peritoneal metastasis (PM) is rare and despite treatment with systemic chemotherapy, the prognosis is poor. However, there is emerging evidence that cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) may offer a survival benefit over systemic therapy alone. This systematic review will assess the effectiveness of CRS-HIPEC for SBA-PM. CONTENT: Three databases were searched from inception to 11/10/21. Clinical outcomes were extracted and analysed. SUMMARY: A total of 164 cases of SBA-PM undergoing CRS-HIPEC were identified in 12 studies. The majority of patients had neoadjuvant chemotherapy (87/164, 53%) and complete cytoreduction (143/164, 87%) prior to HIPEC. The median overall survival was 9-32 months and 5-year survival ranged from 25 to 40%. Clavien-Dindo grade III/IV morbidity ranged between 19.1 and 50%, while overall mortality was low with only 3 treatment-related deaths. OUTLOOK: CRS-HIPEC has the potential to improve the overall survival in a highly selected group of SBA-PM patients, with 5-year survival rates comparable to those reported in colorectal peritoneal metastases. However, the expected survival benefits need to be balanced against the intrinsic risk of morbidity and mortality associated with the procedure. Further multicentre studies are required to assess the safety and feasibility of CRS-HIPEC in SBA-PM to guide best practice management for this rare disease.
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    Prehabilitation in high-risk patients scheduled for major abdominal cancer surgery: a feasibility study
    Waterland, JL ; Ismail, H ; Granger, CL ; Patrick, C ; Denehy, L ; Riedel, B (BMC, 2022-08-23)
    BACKGROUND: Patients presenting for major surgery with low cardiorespiratory fitness (deconditioning) and other modifiable risk factors are at increased risk of postoperative complications. This study investigated the feasibility of delivering prehabilitation in high-risk patients scheduled for major abdominal cancer surgery. METHODS: Eligible patients in this single-center cohort study included patients with poor fitness (objectively assessed by cardiopulmonary exercise testing, CPET) scheduled for elective major abdominal cancer surgery. Patients were recruited to participate in a prehabilitation program that spanned up to 6 weeks pre-operatively and comprised aerobic and resistance exercise training, breathing exercise, and nutritional support. The primary outcome assessed pre-specified feasibility targets: recruitment >70%, retention >85%, and intervention adherence >70%. Secondary outcomes were assessed for improved pre-operative functional status and health-related quality of life and for postoperative complications. RESULTS: Eighty-two (34%) out of 238 patients screened between April 2018 and December 2019 were eligible for recruitment. Fifty (61%) patients (52% males) with a median age of 71 (IQR, 63-77) years participated in the study. Baseline oxygen consumption the at anaerobic threshold and at peak exercise (mean±SD: 9.8±1.8 and 14.0±2.9 mL/kg/min, respectively) confirmed the deconditioned state of the study cohort. The retention rate within the prehabilitation program was 84%, with 42 participants returning for repeat CPET testing. While >60% of participants preferred to do home-based prehabilitation, adherence to the intervention was low-with only 12 (28%) and 15 (35%) of patients having self-reported compliance >70% with their exercise prescriptions. CONCLUSION: Our prehabilitation program in high-risk cancer surgery patients did not achieve pre-specified targets for recruitment, retention, and self-reported program adherence. These findings underpin the importance of implementation research and strategies for the prehabilitation programs in major surgery. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ( ACTRN12620000073909 ) retrospectively registered.
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    Clinical covariates that improve surgical risk prediction and guide targeted prehabilitation: an exploratory, retrospective cohort study of major colorectal cancer surgery patients evaluated with preoperative cardiopulmonary exercise testing
    Bolshinsky, V ; Ismail, H ; Li, M ; Basto, J ; Schier, R ; Hagemeier, A ; Ho, K-M ; Heriot, A ; Riedel, B (BMC, 2022-05-26)
    BACKGROUND: Preoperative risk stratification is used to derive an optimal treatment plan for patients requiring cancer surgery. Patients with reversible risk factors are candidates for prehabilitation programmes. This pilot study explores the impact of preoperative covariates of comorbid disease (Charlson Co-morbidity Index), preoperative serum biomarkers, and traditional cardiopulmonary exercise testing (CPET)-derived parameters of functional capacity on postoperative outcomes after major colorectal cancer surgery. METHODS: Consecutive patients who underwent CPET prior to colorectal cancer surgery over a 2-year period were identified and a minimum of 2-year postoperative follow-up was performed. Postoperative assessment included: Clavien-Dindo complication score, Comprehensive Complication Index, Days at Home within 90 days (DAH-90) after surgery, and overall survival. RESULTS: The Charlson Co-morbidity Index did not discriminate postoperative complications, or overall survival. In contrast, low preoperative haemoglobin, low albumin, or high neutrophil count were associated with postoperative complications and reduced overall survival. CPET-derived parameters predictive of postoperative complications, DAH-90, and reduced overall survival included measures of VCO2 kinetics at anaerobic threshold (AT), peakVO2 (corrected to body surface area), and VO2 kinetics during the post-exercise recovery phase. Inflammatory parameters and CO2 kinetics added significant predictive value to peakVO2 within bi-variable models for postoperative complications and overall survival (P < 0.0001). CONCLUSION: Consideration of modifiable 'triple low' preoperative risk (anaemia, malnutrition, deconditioning) factors and inflammation will improve surgical risk prediction and guide prehabilitation. Gas exchange parameters that focus on VCO2 kinetics at AT and correcting peakVO2 to body surface area (rather than absolute weight) may improve CPET-derived preoperative risk assessment.
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    Laminin 521 enhances self-renewal via STAT3 activation and promotes tumor progression in colorectal cancer
    Qin, Y ; Shembrey, C ; Smith, J ; Paquet-Fifield, S ; Behrenbruch, C ; Beyit, LM ; Thomson, BNJ ; Heriot, AG ; Cao, Y ; Hollande, F (ELSEVIER IRELAND LTD, 2020-04-28)
    Remodeling of basement membrane proteins contributes to tumor progression towards the metastatic stage. One of these proteins, laminin 521 (LN521), sustains embryonic and induced pluripotent stem cell self-renewal, but its putative role in cancer is poorly described. In the present study we found that LN521 promotes colorectal cancer (CRC) cell self-renewal and invasion. siRNA-mediated knockdown of endogenously-produced laminin alpha 5, as well as treatment with neutralizing antibodies against integrin α3β1 and α6β1, were able to reverse the effect of LN521 on self-renewal. Exposure of CRC cells to LN521 enhanced STAT3 phosphorylation, and incubation with STAT3 inhibitors Napabucasin and Stattic was sufficient to block the LN521-driven self-renewal increase. Robust expression of laminin alpha 5 was detected in 7/10 liver metastases tissue sections collected from CRC patients as well as in mouse liver metastasis xenografts, in most cases within areas expressing metastasis cancer stem cell markers such as c-KIT and CD44v6. Finally, retrospective analysis of multiple CRC datasets highlighted the significant association between high LN521 mRNA expression and poor clinical outcome in colorectal cancer patients. Collectively our results indicate that high Laminin 521 expression is a frequent feature of metastatic dissemination in CRC and that it promotes cell invasion and self-renewal, the latter through engagement of integrin isoforms and activation of STAT3 signaling.
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    Management of lateral pelvic lymph nodes by Australasian colorectal surgeons: An insight from the west
    Cribb, B ; Kong, J ; Warrier, S ; McCormick, J ; Heriot, A (WILEY, 2021-12)
    PURPOSE: Lateral pelvic lymph node dissection (LPLND) for locally advanced low rectal cancer is a common practice in Japan. However, it is not widely performed in western countries. The aim of this survey study is to assess the current practice and management of lateral pelvic lymph nodes by colorectal surgeons in Australasia. METHODS: The authors developed a survey to assess surgeons' assessment and management of lateral pelvic lymph nodes in patients with rectal cancer. The survey was run through the online RedCap® platform in 2019. An electronic link and request to complete the survey was sent to specialist surgeons of the Colorectal Surgical Society of Australia and New Zealand (CSSANZ). RESULTS: Ninety-two colorectal surgeons completed the online survey (32% response rate). Eighty percent of participants consider malignant lateral pelvic lymph nodes to represent locoregional and resectable disease. In patients with clinically malignant lateral pelvic lymph nodes on preoperative imaging the majority of respondents (92%) recommend neoadjuvant chemoradiotherapy and 86% would also recommend LPLND. Over half of the surgeons (57%) had no exposure to LPLND during fellowship training and approximately two thirds (62%) do not perform LPLND in their current practice. CONCLUSION: This study highlights the challenges in the management of the lateral pelvic lymph nodes in a western context. The majority of the participating Australasian colorectal surgeons consider malignant lateral pelvic lymph nodes to represent locoregional and resectable disease. The majority also recommend LPLND for clinically malignant lateral pelvic nodes. However, adequate training and experience with LPLND is limited.
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    Are we doing enough to assess surgical quality in advanced colon and rectal cancer?
    Warrier, SK ; Larach, JT ; Kong, JCH ; Waters, PS ; Smart, PJ ; McCormick, JJ ; Heriot, AG (WILEY, 2021-03)
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    Masquerading mucinous metastases: cutaneous colorectal cancer metastasis of the toes
    Larkins, KM ; Heriot, A ; Warrier, SK ; Kong, JC (WILEY, 2021-09)
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    Robotic colorectal surgery in Australia: evolution over a decade
    Larach, JT ; Flynn, J ; Kong, J ; Waters, PS ; McCormick, JJ ; Murphy, D ; Stevenson, A ; Warrier, SK ; Heriot, AG (WILEY, 2021-11)
    BACKGROUND: Despite reports of increasing adoption of robotics in colorectal surgery worldwide, data regarding its uptake in Australasia are lacking. This study examines the trends of robotic colorectal surgery in Australia during the last 10 years. METHODS: Data from patients undergoing robotic colorectal surgery with the da Vinci robotic platform between 2010 and 2019 were obtained. Overall, numbers of specific colorectal procedures across Australia were obtained from the Medicare Benefit Schedule data over the same period. Pearson's correlation analysis was used to determine the statistical trends of overall and specific robotic colorectal procedures over time. RESULTS: A total of 6110 robotic general surgery procedures were performed across Australia during the study period. Of these, 3522 (57.6%) were robotic colorectal procedures. An increasing trend of overall robotic colorectal procedures was seen over 10 years (Pearson's coefficient of 0.875; P = 0.001). While this applied to both the public and private sectors, 90.7% of the procedures were undertaken in the private sector. Restorative rectal resections, rectopexies, and right hemicolectomies accounted for 82.6% of the robotic colorectal procedures performed during this period with an increasing trend seen over time for each intervention. Moreover, a robotic approach was utilized in 12.5%, 41.0% and 9.0% of all restorative rectal resections, rectopexies and right hemicolectomies undertaken in Australia during 2019, respectively. CONCLUSION: Robotic colorectal surgery has increased dramatically in Australia over the last 10 years, especially in the private sector. Penetration of robotic colorectal surgery in the public healthcare system will require focussed cost-benefit evaluations and governmental investment.
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    Oncological reasons for performing a complete mesocolic excision: a systematic review and meta-analysis
    Kong, JC ; Prabhakaran, S ; Choy, KT ; Larach, JT ; Heriot, A ; Warrier, SK (WILEY, 2021-01)
    BACKGROUND: While complete mesocolic excision (CME) has been shown to have an oncological benefit as compared to conventional colonic surgery for colon surgery, this benefit must be weighed up against the risk of major intra-abdominal complications. This paper aimed to assess the comparative oncological benefits of CME. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, a systematic review of the literature until May 2020 was performed. Comparative studies assessing CME versus conventional colonic surgery for colon cancer were compared, and outcomes were pooled. RESULTS: A total of 700 publications were identified, of which 19 were found to meet the inclusion criteria. A total of 25 886 patients were compared, with 14 431 patients in the CME arm. CME was associated with a significantly higher rate of vascular injury (odds ratio 3, P < 0.001). Rates of local and distant recurrence were lower in the CME group (odds ratio 0.66 and 0.73, respectively, both P < 0.001). CME patients had a significantly higher lymph node yield (P < 0.001). While no significant differences were noted between the two groups in terms of pooled 3- or 5-year disease-free survival, pooled 5-year overall survival was significantly higher in the CME group (relative risk 0.82, P < 0.001). CONCLUSION: Based on the available evidence, CME is associated with improved oncologic outcomes at the expense of higher complication rates, including vascular injury. The oncological benefits need to weighed up against a multitude of factors including the level of hospital support, surgeon experience, patient age, and associated comorbidities.