Surgery (Austin & Northern Health) - Research Publications
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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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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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ItemDilemmas and limitations interpreting carbohydrate antigen 19-9 elevation after curative pancreatic surgery: A case report(ELSEVIER SCI LTD, 2019)INTRODUCTION: Serum carbohydrate antigen 19-9 (CA19-9) is routinely used in the management of pancreatic cancer for diagnosis, prognostication and surveillance purposes despite its low specificity. CASE PRESENTATION: This case report demonstrates the challenges of interpreting elevated serum CA19.9 levels in a patient with pancreatic cancer. We performed a Whipple's procedure in an otherwise fit 78-year-old man for pancreatic adenocarcinoma. One year after surgery, he presented with a non-malignant anastomotic stricture that was associated with an elevated serum CA19-9. Subsequently, he presented with biliary sepsis secondary to an infected liver cyst. CA19-9 in the cyst fluid and serum were elevated. On both of these occasions, serum CA19-9 normalised without any clinical or radiological evidence of recurrence. DISCUSSION: Despite sound clinical acumen and investigations, it may be hard to differentiate cancer recurrence from benign aetiologies. Benign conditions may cause elevation of CA19-9, even in the setting of previous malignancy. Persistently high CA19-9 level post-decompression raises suspicion of malignancy. CONCLUSION: This case serves as a reminder for clinicians that non-specific increases in CA19-9 after curative surgery is not uncommon. We recommend careful interpretation of CA19-9 levels in combination with clinical history, physical examination and radiological investigations.
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ItemThe Measurement of Donor-Specific Cell-Free DNA Identifies Recipients With Biopsy-Proven Acute Rejection Requiring Treatment After Liver Transplantation(LIPPINCOTT WILLIAMS & WILKINS, 2019-07)BACKGROUND: Assessment of donor-specific cell-free DNA (dscfDNA) in the recipient is emerging as a noninvasive biomarker of organ rejection after transplantation. We previously developed a digital polymerase chain reaction (PCR)-based approach that readily measures dscfDNA within clinically relevant turnaround times. Using this approach, we characterized the dynamics and evaluated the clinical utility of dscfDNA after liver transplantation (LT). METHODS: Deletion/insertion polymorphisms were used to distinguish donor-specific DNA from recipient-specific DNA. Posttransplant dscfDNA was measured in the plasma of the recipients. In the longitudinal cohort, dscfDNA was serially measured at days 3, 7, 14, 28, and 42 in 20 recipients. In the cross-sectional cohort, dscfDNA was measured in 4 clinically stable recipients (>1-y posttransplant) and 16 recipients (>1-mo posttransplant) who were undergoing liver biopsies. RESULTS: Recipients who underwent LT without complications demonstrated an exponential decline in dscfDNA. Median levels at days 3, 7, 14, 28, and 42 were 1936, 1015, 247, 90, and 66 copies/mL, respectively. dscfDNA was higher in recipients with treated biopsy-proven acute rejection (tBPAR) when compared to those without. The area under the receiver operator characteristic curve of dscfDNA was higher than that of routine liver function tests for tBPAR (dscfDNA: 98.8% with 95% confidence interval, 95.8%-100%; alanine aminotransferase: 85.7%; alkaline phosphatase: 66.4%; gamma-glutamyl transferase: 80.1%; and bilirubin: 35.4%). CONCLUSIONS: dscfDNA as measured by probe-free droplet digital PCR methodology was reflective of organ health after LT. Our findings demonstrate the potential utility of dscfDNA as a diagnostic tool of tBPAR.
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ItemImpact of a goal directed fluid therapy algorithm on postoperative morbidity in patients undergoing open right hepatectomy: a single centre retrospective observational study(BMC, 2019-07-31)BACKGROUND: Right hepatectomy is a complex procedure that carries inherent risks of perioperative morbidity. To evaluate outcome differences between a low central venous pressure fluid intervention strategy and a goal directed fluid therapy (GDFT) cardiac output algorithm we performed a retrospective observational study. We hypothesized that a GDFT protocol would result in less intraoperative fluid administration, reduced complications and a shorter length of hospital stay. METHODS: Patients undergoing hepatectomy using an established enhanced recovery after surgery (ERAS) programme between 2010 and 2017 were extracted from a prospectively managed electronic hospital database. Inclusion criteria included adult patients, undergoing open right (segments V-VIII) or extended right (segments IV-VIII) hepatectomy. PRIMARY OUTCOME: amount of intraoperative fluid administration used between the two groups. SECONDARY OUTCOMES: type and amount of vasoactive medications used, the development of predefined postoperative complications, hospital length of stay, and 30-day mortality. Complications were defined by the European Perioperative Clinical Outcome definitions and graded according to Clavien-Dindo classification. The association between GDFT and the amount of fluid and vasoactive medication used was investigated using logistic and linear regression models. RESULTS: Fifty-eight consecutive patients were identified. 26 patients received GDFT and 32 received Usual care. There were no significant differences in baseline patient characteristics. Less intraoperative fluid was used in the GDFT group: median (IQR) 2000 ml (1175 to 2700) vs. 2750 ml (2000 to 4000) in the Usual care group; p = 0.03. There were no significant differences in the use of vasoactive medications. Postoperative complications were similar: 9 patients (35%) in the GDFT group vs. 18 patients (56%) in the Usual care group; p = 0.10, OR: 0.41; (95%CI: 0.14 to 1.20). Median (IQR) length of stay for patients in the GDFT group was 7 days (6:8) vs. 9 days (7:13) in the Usual care group; incident rate ratio 0.72 (95%CI: 0.56 to 0.93); p = 0.012. There was no difference in perioperative mortality. CONCLUSIONS: In patients undergoing open right hepatectomy with an established ERAS programme, use of GDFT was associated with less intraoperative fluid administration and reduced hospital length of stay when compared to Usual care. There were no significant differences in postoperative complications or mortality. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry: no 12619000558123 on 10/4/19.