Surgery (Austin & Northern Health) - Research Publications

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    The prognostic significance of lymphatics in colorectal liver metastases.
    Muralidharan, V ; Nguyen, L ; Banting, J ; Christophi, C (Hindawi Limited, 2014)
    Background. Colorectal Cancer (CRC) is the most common form of cancer diagnosed in Australia across both genders. Approximately, 40%-60% of patients with CRC develop metastasis, the liver being the most common site. Almost 70% of CRC mortality can be attributed to the development of liver metastasis. This study examines the pattern and density of lymphatics in colorectal liver metastases (CLM) as predictors of survival following hepatic resection for CLM. Methods. Patient tissue samples were obtained from the Victorian Cancer Biobank. Immunohistochemistry was used to examine the spatial differences in blood and lymphatic vessel densities between different regions within the tumor (CLM) and surrounding host tissue. Lymphatic vessel density (LVD) was assessed as a potential prognostic marker. Results. Patients with low lymphatic vessel density in the tumor centre, tumor periphery, and adjacent normal liver demonstrated a significant disease-free survival advantage compared to patients with high lymphatic vessel density (P = 0.01, P > 0.01, and P = 0.05, resp.). Lymphatic vessel density in the tumor centre and periphery and adjacent normal liver was an accurate predictive marker of disease-free survival (P = 0.05). Conclusion. Lymphatic vessel density in CLM appears to be an accurate predictor of recurrence and disease-free survival.
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    Pressurized Pulse Irrigation with Saline Reduces Surgical-site Infections following Major Hepatobiliary and Pancreatic Surgery: Randomized Controlled Trial
    Nikfarjam, M ; Weinberg, L ; Fink, MA ; Muralidharan, V ; Starkey, G ; Jones, R ; Staveley-O'Carroll, K ; Christophi, C (SPRINGER, 2014-02)
    BACKGROUND: Surgical site infections (SSI) are a significant cause of postoperative morbidity. Pressurized pulse irrigation of subcutaneous tissues may lower infection rates by aiding in the debridement of necrotic tissue and reducing bacterial counts compared to simply pouring saline into the wound. METHODS: A total of 128 patients undergoing laparotomy extending beyond 2 h were randomized to treatment of wounds by pressurized pulse lavage irrigation (<15 psi) with 2 L normal saline (pulse irrigation group), or to standard irrigation with 2 L normal saline poured into the wound, immediately prior to skin closure (standard group). Only elective cases were included, and all cases were performed within a specialized hepatobiliary and pancreatic surgery unit. RESULTS: There were 62 patients managed by standard irrigation and 68 were managed by pulse irrigation. The groups were comparable in most aspects. Overall there were 16 (13 %) SSI. Significantly fewer SSI occurred in the pulse irrigation group [4 (6 %) vs. 12 (19 %); p = 0.032]. On multivariate analysis, the use of pulse irrigation was the only factor associated with a reduction in SSI with an odds ratio (OR) of 0.3 [95 % confidence interval (95 % CI) 0.1-0.8; p = 0.031]. In contrast, hospital length of stay of greater than 14 days was associated with increased infections with an OR of 7.6 (95 % CI 2.4-24.9; p = 0.001). CONCLUSIONS: Pulse irrigation of laparotomy wounds in operations exceeding 2 h duration reduced SSI after major hepatobiliary pancreatic surgery. (Australian New Zealand Clinical Trials Registry, ACTRN12612000170820).
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    Blockade of the renin-angiotensin system inhibits growth of colorectal cancer liver metastases in the regenerating liver
    Koh, SL ; Ager, EI ; Costa, PLN ; Malcontenti-Wilson, C ; Muralidharan, V ; Christophi, C (SPRINGER, 2014-04)
    Partial hepatectomy (PH), the preferred option for selected patients with colorectal cancer liver metastases (CRCLM), is associated with 40-80% tumor recurrence rates. Renin-angiotensin system (RAS) blockade inhibits tumor growth and has been suggested to improve liver regeneration. We documented the effect of RAS blockade on tumor growth and liver regeneration in a murine model. CRCLM induction followed by 70% PH was performed on 78 CBA mice. Liver regeneration (days 2, 6) and CRCLM tumor load were measured by liver (and tumor) weights, percentage of CRCLM burden and tumor nodule count (days 16, 21). mRNA expression of the RAS components was characterised. Statistical analysis was performed using 2-independent sample T test or Mann-Whitney test (SPSS). Captopril did not impair liver regeneration. By day 21, Captopril decreased tumor burden (percentage of CRCLM in the liver) (48.7 ± 4.7% control, 24.4 ± 6.2 Captopril; p = 0.008), tumor volume (1046.2 ± 200.2 mm(3), 388.3 ± 150.4; p = 0.02), tumor nodule count per image field (181.1 ± 28.5, 68 ± 17.6; p = 0.005) and tumor angiogenesis (71.8 ± 6.4 vessels/mm(2), 43.1 ± 7.6; p = 0.015) compared to controls. Captopril enhanced tumor apoptosis (1 ± 0.2%, 2.5 ± 0.7; p = 0.028). Liver regeneration and tumor development increased liver ACE levels. Blockade of the RAS effectively retarded CRCLM tumor growth at the late stage of tumor development within the regenerating liver without impeding liver regeneration following PH, via anti-angiogenesis and pro-tumor apoptosis. Captopril may be of therapeutic benefit in patients undergoing PH for CRCLM.