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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ItemA novel immune function biomarker identifies patients at risk of clinical events early following liver transplantation(WILEY, 2017-04)Balancing immunosuppression after liver transplant is difficult, with clinical events common. We investigate whether a novel immune biomarker based on a laboratory platform with widespread availability that measures interferon γ (IFNγ) after stimulation with a lyophilized ball containing an adaptive and innate immune stimulant can predict events following transplantation. A total of 75 adult transplant recipients were prospectively monitored in a blinded, observational study; 55/75 (73.3%) patients experienced a total of 89 clinical events. Most events occurred within the first month. Low week 1 results were significantly associated with risk of early infection (area under the receiver operating characteristic curve [AUROC], 0.74; P = 0.008). IFNγ ≤ 1.30 IU/mL (likelihood ratio positive, 1.93; sensitivity, 71.4%; specificity, 63.0%) was associated with the highest risk for infection with minimal rejection risk. Nearly half the cohort (27/60, 45.0%) expressed IFNγ ≤ 1.30 IU/mL. Moreover, an elevated week 1 result was significantly associated with the risk of rejection within the first month after transplant (AUROC, 0.77; P = 0.002), but no episodes of infection. On multivariate logistic regression, IFNγ ≥ 4.49 IU/mL (odds ratio, 4.75) may be an independent predictor of rejection (P = 0.05). In conclusion, low IFNγ suggesting oversuppression is associated with infections, whereas high IFNγ indicating undersuppression is associated with rejection. This assay offers the potential to allow individualization and optimization of immunosuppression that could fundamentally alter the way patients are managed following transplantation. Liver Transplantation 23 487-497 2017 AASLD.
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ItemIncreasing Incidence of Nonalcoholic Steatohepatitis as an Indication for Liver Transplantation in Australia and New Zealand(LIPPINCOTT WILLIAMS & WILKINS, 2019-01)The worldwide increase in obesity and diabetes has led to predictions that nonalcoholic steatohepatitis (NASH) will become the leading indication for orthotopic liver transplantation (OLT). Data supporting this prediction from outside the United States are limited. Thus, we aimed to determine trends in the frequency of NASH among adults listed and undergoing OLT in Australia and New Zealand (ANZ) from 1994 to 2017. Data from the ANZ Liver Transplant Registry were analyzed with patients listed for fulminant liver failure, retransplantation, or multivisceral transplants excluded. Nonparametric trend, Spearman rank correlation, and regression analysis were used to assess trends in etiologies of liver disease over time. Of 5016 patient wait-list registrants, a total of 3470 received an OLT. The percentage of patients with NASH activated for OLT increased significantly from 2.0% in 2003 to 10.9% in 2017 (trend analyses; P < 0.001). In 2017, NASH was the third leading cause of chronic liver disease (CLD) among wait-list registrants behind chronic hepatitis C virus (HCV; 29.5%) and alcohol (16.1%). Similarly, significant increases over time in the percentage of patients undergoing OLT were observed for HCV and NASH (all trend analyses; P < 0.001) but with significant reductions in primary sclerosing cholangitis and cryptogenic cirrhosis (both P < 0.05). By 2017, NASH was the third leading cause of liver disease among patients undergoing OLT (12.4%) and behind chronic HCV (30.2%) and alcohol (18.2%). NASH also became the third most frequent etiology of CLD in patients transplanted (13.8%) with concomitant hepatocellular carcinoma by 2017. In conclusion, NASH is increasing as a primary etiology of liver disease requiring listing and liver transplantation in ANZ.
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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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ItemEarly viral-specific T-cell testing predicts late cytomegalovirus reactivation following liver transplantation(WILEY, 2018-10)INTRODUCTION: Although antiviral prophylaxis is effective in preventing early cytomegalovirus (CMV) reactivation following liver transplantation (OLT), it predisposes patients to late CMV after prophylaxis has ceased. QuantiFERON-CMV (QFN-CMV, Qiagen, The Netherlands) measures an individual's viral-specific immune response. METHODS: Fifty-nine OLT recipients were prospectively monitored post-OLT in an observational cohort study. QFN-CMV was performed at regular time-points. An absolute QFN-CMV <0.1 IU/mL was considered non-reactive. RESULTS: 50/59 (84.7%) had a reactive QFN-CMV by M6. 38/59 (64.4%) had antiviral prophylaxis or treatment before M6, with 31/38 (81.6%) developing a reactive QFN-CMV by 6 months. Over 90% already had a reactive result as early as 3 months post transplant, 3 patients (5.08%) developed late CMV between 6-12 months (median 251 days)-all had a non-reactive M6 QFN-CMV. And 2/3 experienced CMV disease. Non-reactive M6 QFN-CMV was significantly associated with late CMV (OR = 54.4, PPV = 0.33, NPV = 1.00, P = .003). CONCLUSION: Although only 5% of recipients developed late CMV, 2/3 suffered CMV disease. M6 QFN-CMV has an excellent NPV for late CMV, suggesting patients who exhibit a robust ex vivo immune response at M6 can safely cease CMV monitoring. Furthermore, >90% already express viral-specific immunity as early as 3 months. Conceivably, antiviral prophylaxis could be discontinued early in these patients.
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ItemExcellent Contemporary Graft Survival for Adult Liver Retransplantation: An Australian and New Zealand Registry Analysis From 1986 to 2017.(Ovid Technologies (Wolters Kluwer Health), 2019-08)BACKGROUND: Liver retransplantation is technically challenging, and historical outcomes are significantly worse than for first transplantations. This study aimed to assess graft and patient survival in all Australian and New Zealand liver transplantation units. METHODS: A retrospective cohort analysis was performed using data from the Australia and New Zealand Liver Transplant Registry. Graft and patient survival were analyzed according to era. Cox regression was used to determine recipient, donor, or intraoperative variables associated with outcomes. RESULTS: Between 1986 and 2017, Australia and New Zealand performed 4514 adult liver transplants, 302 (6.7%) of which were retransplantations (278 with 2, 22 with 3, 2 with 4). The main causes of graft failure were hepatic artery or portal vein thrombosis (29%), disease recurrence (21%), and graft nonfunction (15%). Patients retransplanted after 2000 had a graft survival of 85% at 1 year, 75% at 5 years, and 64% at 10 years. Patient survival was 89%, 81%, and 74%, respectively. This was higher than retransplantations before 2000 (P < 0.001). Univariate analysis found that increased recipient age (P = 0.001), recipient weight (P = 0.019), and donor age (P = 0.011) were associated with decreased graft survival prior to 2000; however, only increased patient weight was significant after 2000 (P = 0.041). Multivariate analysis found only increased recipient weight (P = 0.042) and donor age (P = 0.025) was significant prior to 2000. There was no difference in survival for second and third retransplants or comparing time to retransplant. CONCLUSIONS: Australia and New Zealand have excellent survival following liver retransplantation. These contemporary results should be utilized for transplant waitlist methods.
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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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ItemEpidemiology and outcomes of acute liver failure in Australia(BAISHIDENG PUBLISHING GROUP INC, 2019-07-27)BACKGROUND: Acute liver failure (ALF) is a life-threatening syndrome with varying aetiologies requiring complex care and multidisciplinary management. Its changing incidence, aetiology and outcomes over the last 16 years in the Australian context remain uncertain. AIM: To describe the changing incidence, aetiology and outcomes of ALF in South Eastern Australia. METHODS: The database of the Victorian Liver Transplant Unit was interrogated to identify all cases of ALF in adults (> 16 years) in adults hospitalised between January 2002 and December 2017. Overall, 169 patients meeting criteria for ALF were identified. Demographics, aetiology of ALF, rates of transplantation and outcomes were collected for all patients. Transplant free survival and overall survival (OS) were assessed based on survival to discharge from hospital. Results were compared to data from a historical cohort from the same unit from 1988-2001. RESULTS: Paracetamol was the most common aetiology of acute liver failure, accounting for 50% of cases, with an increased incidence compared with the historical cohort (P = 0.046). Viral hepatitis and non-paracetamol drug or toxin induced liver injury accounted for 15% and 10% of cases respectively. Transplant free survival (TFS) improved significantly compared to the historical cohort (52% vs 38%, P = 0.032). TFS was highest in paracetamol toxicity with spontaneous recovery in 72% of cases compared to 31% of non-paracetamol ALF (P < 0.001). Fifty-nine patients were waitlisted for emergency liver transplantation. Nine of these died while waiting for an organ to become available. Forty-two patients (25%) underwent emergency liver transplantation with a 1, 3 and 5 year survival of 81%, 78% and 72% respectively. CONCLUSION: Paracetamol toxicity is the most common aetiology of ALF in South-Eastern Australia with a rising incidence over 30 years. TFS has improved, however it remains low in non-paracetamol ALF.
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ItemIntraoperative TOE guided management of newly diagnosed severe tricuspid regurgitation and pulmonary hypertension during orthotopic liver transplantation: a case report demonstrating the importance of reversibility as a favorable prognostic factor(BMC, 2019-07-13)BACKGROUND: Tricuspid regurgitation (TR) and pulmonary hypertension (PHT) are highly dynamic cardiovascular lesions that may progress rapidly, particularly in the orthotopic liver transplantation (OLT) waitlist population. Severe TR and PHT are associated with poor outcomes in these patients, however it is rare for the two to be newly diagnosed intraoperatively at the time of OLT. Without preoperative information on pulmonary vascular and right heart function, the potential for reversibility of severe TR and PHT is unclear, making the decision to proceed to transplant fraught with difficulty. CASE PRESENTATION: We present a case of successful orthotopic liver transplantation (OLT) in a 48 year old female with severe (PHT) (mean pulmonary arterial pressure > 55 mmHg) and severe TR diagnosed post induction of anaesthesia. The degree of TR was associated with systemic venous pressures of > 100 mmHg resulting in massive haemorrhage during surgery and difficulty in distinguishing venous from arterial placement of vascular access devices. Intraoperative transoesophageal echocardiography (TOE) proved crucial in diagnosing functional TR due to tricuspid annular and right ventricular (RV) dilatation, and dynamically monitoring response to treatment. In response to positioning, judicious volatile anaesthesia administration, pulmonary vasodilator therapy and permissive hypovolemia during surgery we noted substantial improvement of the TR and pulmonary arterial pressures, confirming the reversibility of the TR and associated PHT. CONCLUSION: TR and PHT are co-dependent, dynamic, load sensitive right heart conditions that are interdependent with chronic liver disease, and may progress rapidly in patients waitlisted for OLT. Use of intraoperative TOE and pulmonary artery catheterisation on the day of surgery will detect previously undiagnosed severe TR and PHT, enable rapid assessment of the cause and the potential for reversibility. These dynamic monitors permit real-time assessment of the response to interventions or events affecting right ventricular (RV) preload and afterload, providing critical information for prognosis and management. Furthermore, we suggest that TR and PHT should be specifically sought when waitlisted OLT patients present with hepatic decompensation.
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ItemActivation of the Alternate Renin-Angiotensin System Correlates with the Clinical Status in Human Cirrhosis and Corrects Post Liver Transplantation(MDPI, 2019-04)INTRODUCTION: Recent animal studies have shown that the alternate renin-angiotensin system (RAS) consisting of angiotensin-converting enzyme 2 (ACE2), angiotensin-(1⁻7) (Ang-(1⁻7)) and the Mas receptor is upregulated in cirrhosis and contributes to splanchnic vasodilatation and portal hypertension. To determine the potential relevance of these findings to human liver disease, we evaluated its expression and relationship to the patients' clinical status in subjects with cirrhosis. METHODS: Blood sampling from peripheral and central vascular beds was performed intra-operatively for cirrhotic patients at the time of liver transplantation (LT) or trans-jugular intra-hepatic portosystemic shunt (TIPS) procedures to measure angiotensin II (Ang II) and Ang-(1⁻7) peptide levels and ACE and ACE2 enzyme activity. Relevant clinical and hemodynamic data were recorded pre-operatively for all subjects and peripheral blood sampling was repeated 3 months or later post-operatively. RESULTS: Ang-(1⁻-7) and ACE2 activity were up-regulated more than twofold in cirrhotic subjects both at the time of LT and TIPS and levels returned to comparable levels as control subjects post-transplantation. Ang-(1⁻7) levels correlated positively with the degree of liver disease severity, as measured by the model for an end-stage liver disease (MELD) and also with clinical parameters of pathological vasodilatation including cardiac output (CO). There were strong correlations found between the ACE2:ACE and the Ang-(1⁻7):Ang II ratio highlighting the inter-dependence of the alternate and classical arms of the RAS and thus their potential impact on vascular tone. CONCLUSIONS: In human cirrhosis, the alternate RAS is markedly upregulated and the activation of this system is associated strongly with features of the hyperdynamic circulation in advanced human cirrhosis.