Surgery (Austin & Northern Health) - Research Publications
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ItemCaptopril, a Renin-Angiotensin System Inhibitor, Attenuates Tumour Progression in the Regenerating Liver Following Partial Hepatectomy(MDPI, 2022-05)(1) Liver regeneration following partial hepatectomy for colorectal liver metastasis (CRLM) has been linked to tumour recurrence. Inhibition of the renin−angiotensin system (RASi) attenuates CRLM growth in the non-regenerating liver. This study investigates whether RASi exerts an antitumour effect within the regenerating liver following partial hepatectomy for CRLM and examines RASi-induced changes in the tumour immune microenvironment; (2) CRLM in mice was induced via intrasplenic injection of mouse colorectal tumour cells, followed by splenectomy on Day 0. Mice were treated with RASi captopril (250 mg/kg/day), or saline (control) from Day 4 to Day 16 (endpoint) and underwent 70% partial hepatectomy on Day 7. Liver and tumour samples were characterised by flow cytometry and immunofluorescence; (3) captopril treatment reduced tumour burden in mice following partial hepatectomy (p < 0.01). Captopril treatment reduced populations of myeloid-derived suppressor cells (MDSCs) (CD11b+Ly6CHi p < 0.05, CD11b+Ly6CLo p < 0.01) and increased PD-1 expression on infiltrating hepatic tissue-resident memory (TRM)-like CD8+ (p < 0.001) and double-negative (CD4-CD8-; p < 0.001) T cells; (4) RASi reduced CRLM growth in the regenerating liver and altered immune cell composition by reducing populations of immunosuppressive MDSCs and boosting populations of PD-1+ hepatic TRMs. Thus, RASi should be explored as an adjunct therapy for patients undergoing partial hepatectomy for CRLM.
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ItemSerum carbohydrate antigen 19-9 in pancreatic adenocarcinoma: a mini review for surgeons(WILEY, 2017-12)The optimal management of oncological conditions is reflected by the careful interpretation of investigations for screening, diagnosis, staging, prognostication and surveillance. Serum tumour markers are examples of commonly requested tests in conjunction with other imaging and endoscopic tests that are used to help clinicians to stratify therapeutic decisions. Serum carbohydrate antigen 19-9 (CA19-9) is a key biomarker for pancreatic cancers. Although this biomarker is considered clinically useful and informative, clinicians are often challenged by the accurate interpretation of elevated serum CA19-9 levels. Recognizing the pitfalls of normal and abnormal serum CA19-9 concentrations will facilitate its appropriate use. In this review, we appraised the biomarker, serum CA19-9, and highlighted the clinical utility and limitations of serum CA19-9 in the investigation and management of pancreatic cancers.
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ItemAge 80 years and over is not associated with increased morbidity and mortality following pancreaticoduodenectomy(WILEY, 2018-05)BACKGROUND: Pancreaticoduodenectomy (PD) is associated with high morbidity, which is perceived to be increased in the elderly. To our knowledge there have been no Australian series that have compared outcomes of patients over the age of 80 undergoing PD to those who are younger. METHODS: Patients who underwent PD between January 2008 and November 2015 were identified from a prospectively maintained database. RESULTS: A total of 165 patients underwent PD of whom 17 (10.3%) were aged 80 or over. The pre-operative health status, according to American Society of Anesthesiologists class was similar between the groups (P = 0.420). The 90-day mortality rates (5.9% in the elderly and 2% in the younger group; P = 0.355) and the post-operative complication rates (64.7% in the elderly versus 62.8% in the younger group; P = 0.88) were similar. Overall median length of hospital stay was also similar between the groups, but older patients were far more likely to be discharged to a rehabilitation facility than younger patients (47.1 versus 12.8%; P < 0.0001). Older patients with pancreatic adenocarcinoma (n = 10) had significantly lower median survival than the younger group (n = 69) (16.6 versus 22.5 months; P = 0.048). CONCLUSION: No significant differences were seen in the rate of complications following PD in patients aged 80 or over compared to younger patients, although there appears to be a shorter survival in the elderly patients treated for pancreatic cancer. Careful selection of elderly patients and optimal peri-operative care, rather than age should be used to determine whether surgical intervention is indicated in this patient group.
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ItemAcute cholangitis: current concepts(WILEY, 2017-07)BACKGROUND: Acute cholangitis, also known as ascending cholangitis, is a life-threatening systemic condition that results from a biliary tree infection and obstruction. Severe acute cholangitis was reported to have a mortality rate between 11 and 27% in the 1990s. This article is a literature review about acute cholangitis. Its aim is to review the latest literature about acute cholangitis and to discuss its pathogenesis, clinical presentation, diagnosis, prognosis, risk factors and treatment. METHODS: Ovid Medline and PubMed database searches were performed for articles about acute cholangitis published in English from 1877 to 2016. The keyword search headings included 'acute', 'ascending' and 'cholangitis', and a combination of these were used. Only articles with full-text descriptions were chosen for this literature review. RESULTS: Common causes of biliary tree obstruction include choledocholithiasis, benign and malignant biliary strictures. According to the Tokyo Guidelines, clinical presentation, laboratory blood results and diagnostic imaging are important in the diagnosis of acute cholangitis. Treatments consist of intravenous fluids and antibiotics followed by biliary decompression and drainage. Available drainage options include endoscopic retrograde cholangiopancreatography, percutaneous transhepatic cholangiography, endoscopic ultrasound and open surgical drainage. CONCLUSION: It is important to diagnose acute cholangitis as early as possible to initiate appropriate treatments to reduce mortality and morbidity.
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ItemMetabolic response evaluation for colorectal liver metastases and correlation to pathologic response and tumour markers(WILEY, 2018-03)BACKGROUND: Tumour metabolic response to chemotherapy is increasingly recognized as a prognostic indicator for colorectal cancer liver metastases (CRCLM). However, its clinical role and the underlying biological mechanism of its prognostic ability are unclear. This study compares metabolic to pathologic response for CRCLM, and correlates metabolic response to tumour expression of six key biomarkers. METHODS: Thirty-seven patients who had positron emission tomography imaging before and after pre-operative chemotherapy prior to liver resection for CRCLM were included. Metabolic response was assessed according to the positron emission tomography response criteria in solid tumours (PERCIST) and correlated to recurrence-free and overall survival. PERCIST was compared to tumour regression grading, computed tomography (CT) response, tumour necrosis and mucin and immunohistochemical expression of Ki-67, hypoxia inducible factor 1α, vascular endothelial growth factor, p53, p16 and vimentin. Area under the receiver operating characteristic curve (AUC), Kaplan-Meier survival, Spearman's correlation (rs ) and multivariate Cox regression analyses were used. RESULTS: PERCIST correlated significantly to 2-year mortality (AUC = 0.162, P < 0.01) and 2-year recurrence (AUC = 0.284, P = 0.03). Metabolically responsive tumours conferred a better overall survival (P = 0.01) and recurrence-free survival (P = 0.03). Tumour regression grading did not stratify for outcome. Metabolic response was significantly correlated to Ki-67 and p16 expression (rs = 0.559 and rs = -0.549, respectively). Multivariate analysis revealed only PERCIST to be correlated to death and recurrence. CONCLUSION: Pre-operative PERCIST assessment of CRCLM was more prognostic than pathologic and CT response assessment. Metabolic non-response correlated with tumour proliferation and loss of tumour suppression.
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ItemSearching for the link; mechanisms underlying liver regeneration and recurrence of colorectal liver metastasis post partial hepatectomy(WILEY, 2019-08)Despite excellent treatment of primary colorectal cancer, the majority of deaths occur as a result of metastasis to the liver. Recent population studies have estimated that one quarter of patients with colorectal cancer will incur synchronous or metachronous colorectal liver metastasis. However, only one quarter of these patients will be eligible for potentially curative resection. Tumor recurrence occurs in reportedly 60% of patients undergoing hepatic resection, and the majority of intrahepatic recurrence occurs within the first 6 months of surgery. The livers innate ability to restore its homeostatic size, and volume facilitates major hepatic resection that currently offers the only chance of cure to patients with extensive hepatic metastases. Experimental and clinical evidence supports the notion that following partial hepatectomy, liver regeneration (LR) paradoxically drives tumor progression and increases the risk of recurrence. It is becoming increasingly clear that the processes that drive liver organogenesis, regeneration, and tumor progression are inextricably linked. This presents a major hurdle in the management of colorectal liver metastasis and other hepatic malignancies because therapies that reduce the risk of recurrence without hampering LR are sought. The processes and pathways underlying these phenomena are multiple, complex, and cross-communicate. In this review, we will summarize the common mechanisms contributing to both LR and tumor recurrence.
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ItemBile duct resection for eosinophilic cholangitis(WILEY, 2019-11)
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ItemEmergency presentations of acute biliary pain: changing patterns of management in a tertiary institute(WILEY, 2018-12)BACKGROUND: Acute biliary pain is the most common presentation of gallstone disease. Untreated patients risk recurrent pain, cholecystitis, obstructive jaundice, pancreatitis and multiple hospital presentations. We examine the outcome of implementing a policy to offer laparoscopic cholecystectomy on index presentation to patients with biliary colic in a tertiary hospital in Australia. METHODS: This is a retrospective cohort study of adult patients presenting to the emergency department (ED) with biliary pain during three 12-month periods. Outcomes in Group A, 3 years prior to policy implementation, were compared with groups 2 and 7 years post implementation (Groups B and C). Primary outcomes were representations to ED, admission rate and time to cholecystectomy. RESULTS: A total of 584 patients presented with biliary colic during the three study periods. Of these, 391 underwent cholecystectomy with three Strasberg Type A bile leaks and no bile duct injuries. The policy increased admission rates (A = 15.8%, B = 62.9%, C = 29.5%, P < 0.001) and surgery on index presentation (A = 12.0%, B = 60.7%, C = 27.4%, P < 0.001). There was a decline in time to cholecystectomy (days) (A = 143, B = 15, C = 31, P < 0.001), post-operative length of stay (days) (A = 3.6, B = 3.2, C = 2.0, P < 0.05) and representation rates to ED (A = 42.1%, B = 7.1%, C = 19.9%, P < 0.001). There was a decline in policy adherence in the later cohort. CONCLUSION: Index hospital admission and cholecystectomy for biliary colic decrease patient representations, time to surgery, post-operative stay and complications of gallstone disease. This study demonstrates the impact of the policy with initial improvement, the dangers of policy attrition and the need for continued reinforcement.
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