Surgery (St Vincent's) - Research Publications

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    Impact of the approach on conversion to open surgery during minimally invasive restorative total mesorectal excision for rectal cancer
    Larach, JT ; Kong, J ; Flynn, J ; Wright, T ; Mohan, H ; Waters, PS ; McCormick, JJ ; Warrier, SK ; Heriot, AG (SPRINGER, 2023-03-27)
    BACKGROUND: The aim of this study is to explore the impact of the approach on conversion in patients undergoing minimally invasive restorative total mesorectal excision within a single unit. METHODS: A retrospective cohort study was conducted. Patients with rectal cancer undergoing minimally invasive restorative total mesorectal excision between January 2006 and June 2020 were included. Subjects were classified according to the presence or absence of conversion. Baseline variables and short-term outcomes were compared. Regression analyses were conducted to assess the relationship between the approach and conversion. RESULTS: During the study period, 318 patients underwent a restorative proctectomy. Of these, 240 met the inclusion criteria. Robotic and laparoscopic approaches were undertaken in 147 (61.3%) and 93 (38.8%) cases, respectively. A transanal approach was utilised in 62 (25.8%) cases (58.1% in combination with a robotic transabdominal approach). Conversion to open surgery occurred in 30 cases (12.5%). Conversion was associated with an increased overall complication rate (P = 0.003), surgical complications (P = 0.009), superficial surgical site infections (P = 0.02) and an increased length of hospital stay (P = 0.006). Robotic and transanal approaches were both associated with decreased conversion rates. The multiple logistic regression analysis, however, showed that only a transanal approach was independently associated with a lower risk of conversion (OR 0.147, 0.023-0.532; P = 0.01), whilst obesity was an independent risk factor for conversion (OR 4.388, 1.852-10.56; P < 0.00). CONCLUSIONS: A transanal component is associated with a reduced conversion rate in minimally invasive restorative total mesorectal excision, regardless of the transabdominal approach utilised. Larger studies will be required to confirm these findings and define which subgroup of patients could benefit from transanal component when a robotic approach is undertaken.
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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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    What are clinically relevant performance metrics in robotic surgery? A systematic review of the literature
    Younes, MM ; Larkins, K ; To, G ; Burke, G ; Heriot, A ; Warrier, S ; Mohan, H (SPRINGERNATURE, 2023-04)
    A crucial element of any surgical training program is the ability to provide procedure-specific, objective, and reliable measures of performance. During robotic surgery, objective clinically relevant performance metrics (CRPMs) can provide tailored contextual feedback and correlate with clinical outcomes. This review aims to define CRPMs, assess their validity in robotic surgical training and compare CRPMs to existing measures of robotic performance. A systematic search of Medline and Embase databases was conducted in May 2022 following the PRISMA guidelines. The search terms included Clinically Relevant Performance Metrics (CRPMs) OR Clinically Relevant Outcome Measures (CROMs) AND robotic surgery. The study settings, speciality, operative context, study design, metric details, and validation status were extracted and analysed. The initial search yielded 116 citations, of which 6 were included. Citation searching identified 3 additional studies, resulting in 9 studies included in this review. Metrics were defined as CRPMs, CROMs, proficiency-based performance metrics and reference-procedure metrics which were developed using a modified Delphi methodology. All metrics underwent both contents and construct validation. Two studies found a strong correlation with GEARS but none correlated their metrics with patient outcome data. CRPMs are a validated and objective approach for assessing trainee proficiency. Evaluating CRPMs with other robotic-assessment tools will facilitate a multimodal metric evaluation approach to robotic surgery training. Further studies should assess the correlation with clinical outcomes. This review highlights there is significant scope for the development and validation of CRPMs to establish proficiency-based progression curricula that can be translated from a simulation setting into clinical practice.
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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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    Tight Junction Protein Claudin-2 Promotes Self-Renewal of Human Colorectal Cancer Stem-like Cells
    Paquet-Fifield, S ; Koh, SL ; Cheng, L ; Beyit, LM ; Shembrey, C ; Molck, C ; Behrenbruch, C ; Papin, M ; Gironella, M ; Guelfi, S ; Nasr, R ; Grillet, F ; Prudhomme, M ; Bourgaux, J-F ; Castells, A ; Pascussi, J-M ; Heriot, AG ; Puisieux, A ; Davis, MJ ; Pannequin, J ; Hill, AF ; Sloan, EK ; Hollande, F (American Association for Cancer Research, 2018-06-01)
    Posttreatment recurrence of colorectal cancer, the third most lethal cancer worldwide, is often driven by a subpopulation of cancer stem cells (CSC). The tight junction (TJ) protein claudin-2 is overexpressed in human colorectal cancer, where it enhances cell proliferation, colony formation, and chemoresistance in vitro. While several of these biological processes are features of the CSC phenotype, a role for claudin-2 in the regulation of these has not been identified. Here, we report that elevated claudin-2 expression in stage II/III colorectal tumors is associated with poor recurrence-free survival following 5-fluorouracil–based chemotherapy, an outcome in which CSCs play an instrumental role. In patient-derived organoids, primary cells, and cell lines, claudin-2 promoted colorectal cancer self-renewal in vitro and in multiple mouse xenograft models. Claudin-2 enhanced self-renewal of ALDHHigh CSCs and increased their proportion in colorectal cancer cell populations, limiting their differentiation and promoting the phenotypic transition of non-CSCs toward the ALDHHigh phenotype. Next-generation sequencing in ALDHHigh cells revealed that claudin-2 regulated expression of nine miRNAs known to control stem cell signaling. Among these, miR-222-3p was instrumental for the regulation of self-renewal by claudin-2, and enhancement of this self-renewal required activation of YAP, most likely upstream from miR-222-3p. Taken together, our results indicate that overexpression of claudin-2 promotes self-renewal within colorectal cancer stem-like cells, suggesting a potential role for this protein as a therapeutic target in colorectal cancer.
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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)