Association of physiological reserve measures with adverse outcomes following liver transplantation.

BACKGROUND AND AIM: The comparative utility of physiological reserve measures in predicting important clinical outcomes following liver transplantation (LT) requires further study. The aim of this work was therefore to compare the utility of physiological reserve measures in predicting early adverse clinical outcomes post-LT. METHODS: A single-center, retrospective cohort study of LT patients consecutively recruited between 1 January 2015, and 31 August 2020. Outcomes measured were sepsis and death within 12 months of LT, hospital length of stay (LOS), and intensive care LOS. Physiological reserve measures were handgrip strength, mid-arm muscle circumference, and cardiopulmonary exercise testing (CPET) measures. Analysis was performed using univariate and multivariate logistic regression for sepsis and death, and univariate and multivariate Cox regression for hospital and intensive care LOS. RESULTS: Data were obtained for 109 subjects. Patients were predominantly (64%) male with a median (interquartile range [IQR]) age of 57 (49-63) and median (IQR) Model for End-Stage Liver Disease score of 16 (11-21). In multivariate analysis, the odds of sepsis were lower in patients in the highest versus lowest tertile (odds ratio = 0.004; 95% confidence interval [CI] 0.00-0.13; P = 0.002). Hospital LOS was linearly associated with handgrip strength (hazard ratio [HR] = 1.03; 95% CI 1.00-1.06; P = 0.03) in multivariate analysis. Intensive care LOS was associated with peak VO2 (HR 1.83; 95% CI 1.06-3.16; P = 0.03) and VE/VCO2 slope (HR 0.71; 95% CI 0.58-0.88; P = 0.002) in multivariate analysis. CONCLUSION: Handgrip strength and CPET both identify candidates at high risk of adverse outcomes after LT.

Cardiovascular mortality following liver transplantation: predictors and temporal trends over 30 years.

AIMS: There has been significant evolution in operative and post-transplant therapies following liver transplantation (LT). We sought to study their impact on cardiovascular (CV) mortality, particularly in the longer term. METHODS AND RESULTS: A retrospective cohort study was conducted of all adult LTs in Australia and New Zealand across three 11-year eras from 1985 to assess prevalence, modes, and predictors of early (≤30 days) and late (>30 days) CV mortality. A total of 4265 patients were followed-up for 37 409 person-years. Overall, 1328 patients died, and CV mortality accounted for 228 (17.2%) deaths. Both early and late CV mortality fell significantly across the eras (P < 0.001). However, CV aetiologies were consistently the leading cause of early mortality and accounted for ∼40% of early deaths in the contemporary era. Cardiovascular deaths occurred significantly later than non-cardiac aetiologies (8.8 vs. 5.2 years, P < 0.001). On multivariable Cox regression, coronary artery disease [hazard ratio (HR) 4.6, 95% confidence interval (CI) 1.2-21.6; P = 0.04] and era of transplantation (HR 0.44; 95% CI 0.28-0.70; P = 0.01) were predictors of early CV mortality, while advancing age (HR 1.05, 95% CI 1.02-1.10; P = 0.005) was an independent predictors of late CV mortality. Most common modes of CV death were cardiac arrest, cerebrovascular events, and myocardial infarction. CONCLUSION: Despite reductions in CV mortality post-LT over 30 years, they still account for a substantial proportion of early and late deaths. The late occurrence of CV deaths highlights the importance of longitudinal follow-up to study the efficacy of targeted risk-reduction strategies in this unique patient population.

Endoscopic cyst-gastrostomy for pancreatic pseudocysts: refining the indications.

BACKGROUND: Pseudocysts are a common consequence of acute pancreatitis and require intervention if symptomatic. Endoscopic management is emerging as a safe and effective alternative to surgery, although its use is not yet widespread. METHODS: We describe our experience of 10 consecutive unselected patients who underwent endoscopic ultrasound-guided cyst-gastrostomy and stent insertion at a tertiary referral centre. Technical aspects of the procedure are detailed with accompanying photographs. RESULTS: Six patients made an uneventful recovery. Four patients developed complications, of which one was successfully salvaged by endoscopy and three required surgery. CONCLUSION: We discuss technical and patient factors which may have contributed to these complications in the context of current literature, and in particular, found that the presence of necrosis was associated with higher morbidity, both in our series and in others. In our experience, endoscopic ultrasound-guided cyst-gastrostomy is best employed in simple, mature pseudocysts without necrotic debris, and we recommend this procedure only after a detailed assessment of the pseudocyst in a specialist hepatobiliary unit.

Hepatocellular carcinoma in Australia's Northern Territory: high incidence and poor outcome.

OBJECTIVE: To describe the epidemiology, clinical features, management and outcomes of hepatocellular carcinoma (HCC) in the Northern Territory over the past decade. DESIGN, SETTING AND PATIENTS: An NT-wide epidemiology study covering the period 1991-2010 and a clinical cohort study including patients diagnosed during 2000-2011. HCC diagnoses were provided by the NT Cancer Registry and cross-checked against clinical records. MAIN OUTCOME MEASURES: Age-adjusted incidence of HCC; management; clinical features; and median and 1-year survival. RESULTS: There were 145 incident cases of HCC in the NT during 1991-2010, giving an age-adjusted annual incidence of 22.7/100 000 (95% CI, 17.2-26.8) for Indigenous Australians and 4.0/100 000 (95% CI, 2.1-5.8) for non-Indigenous Australians - an incidence rate ratio of 5.9 (95% CI, 4.7-7.4). There was no significant change in annual age-adjusted incidence over this period. The most common causative factors were hepatitis B virus in Indigenous people and hepatitis C virus in non-Indigenous people. Most people were diagnosed late, only 13/80 were diagnosed by screening, and outcomes were poor, with 28/80 overall surviving to 1 year. Outcomes were better among those managed through a centralised multidisciplinary service than among those who were not (adjusted hazard ratio for death at 1 year, 0.35 [95% CI, 0.16-0.81]). CONCLUSION: HCC incidence remains high in the Indigenous people of the NT. More resources are needed for HCC surveillance and management programs in this population.

Cancer in liver transplant recipients: management and outcomes.

AIM: To investigate the management and cancer outcomes of liver transplant recipients. METHOD: An audit of all liver transplant recipients from a single liver transplant center from January 1991 to March 2010. Data were obtained from case notes, cancer registry and clinical databases. RESULTS: 198 transplant recipients were identified and 49 (25%) were confirmed as having post-transplantation malignancies. Of these 32 (16%) patients developed skin malignancies and 17 (9%) developed post-transplant non-skin malignancies. All skin malignancies had local involvement only and none of the patients with skin malignancies developed nodal or distant metastases. All were managed with local treatment. Of those with non-cutaneous malignancies, four were managed with local therapy alone, two with immunosuppression reduction, seven with chemotherapy, including two with chemoradiotherapy, one with a targeted agent and three with supportive care only. None of the patients who were treated with chemotherapy for non-skin malignancies were able to complete the full prescribed dose of chemotherapy as a result of chemotherapy-related toxicities. Of those treated with chemotherapy one died of hepatic failure and one of chemotherapy-related infection. CONCLUSION: Liver transplant recipients are at high risk of cancer. Outcomes for liver transplant recipients with post-transplant malignancy are excellent if detected when they are amenable to local therapy alone. Outcomes are poor, with high rates of treatment-associated toxicity, in patients who require systemic therapy. Further research is required to enable the development of guidelines for the safe administration of systemic treatment in this group.

Cirrhosis and microvascular invasion predict outcomes in hepatocellular carcinoma.

BACKGROUND: Liver resection (LR) and liver transplantation (LT) are two modalities offering potential for cure in patients with hepatocellular carcinoma (HCC). The objective of this study was to evaluate the long-term survival of patients with HCC treated with LT and LR and to analyse variables influencing these outcomes. METHODS: Patients referred to the South Australian Liver Transplant Unit and Hepatopancreatobiliary Unit at Flinders Medical Centre from January 1992 to September 2009 with a diagnosis of HCC who underwent LT or LR were included in the study. Histopathological parameters analysed included size, number and grade of tumour, microscopic vascular invasion and presence or absence of cirrhosis in remnant liver. RESULTS: Eighty-five patients with a median age of 58 years (range 26-85 years) underwent LT or LR. Median follow-up was 40 months in both groups. Overall, 5-year actuarial survival for all patients with HCC in both groups was 55%. LR patients were significantly older (P < 0.001) than LT patients. Their tumours were larger (P < 001) and more often solitary (P < 0.001) compared with the LT group. In multivariate analysis, age >60 (P < 0.02), histopathological evidence of vascular invasion (P < 0.02) and presence of cirrhosis (P < 0.02) were associated with a significantly reduced survival. Patients without vascular invasion and cirrhosis had an actuarial 5-year survival >70%. CONCLUSIONS: Our study indicates that LT (within University of California, San Francisco criteria) and LR can lead to acceptable long-term survival outcomes in patients with HCC. Microscopic vascular invasion and cirrhosis were the most significant prognostic factors impacting on survival.

Predicting patient survival after pancreaticoduodenectomy for malignancy: histopathological criteria based on perineural infiltration and lymphovascular invasion.

BACKGROUND: Accurate and simple prognostic criteria based on histopathology following pancreaticoduodenectomy would be helpful in assessing prognosis and considering and evaluating adjuvant therapy. This study analysed the histological parameters influencing outcome following pancreaticoduodenectomy for periampullary malignancy. METHODS: A total of 110 pancreaticoduodenectomies were performed from 1998 to 2008. The median age of patients was 69 years (range 20-89 years). The median follow-up was 4.9 years. Of the procedures, 87% (96) were performed for malignancies and the remainder (n= 14) for benign aetiologies. Of the 96 malignancies, 60 were pancreatic adenocarcinoma and the rest were ampullary (14), cholangio (9), duodenal (9) carcinomas and others. Statistical analysis was performed using log-rank and Cox regression multivariate analyses. RESULTS: Patients who underwent resection had 1-, 3- and 5-year survival rates of 70%, 46% and 41%, respectively. The 1-, 3- and 5-year survival rates for periampullary cancers other than pancreatic adenocarcinoma were 83%, 69% and 61%, respectively; those for pancreatic adenocarcinoma were 62%, 31% and 27%, respectively (P < 0.003). Poor tumour differentiation (P < 0.02), tumour size >3 cm (P < 0.04), margin

Influence of resection margin on survival in hepatic resections for colorectal liver metastases.

BACKGROUND: Traditionally a 1-cm margin has been accepted as the gold standard for resection of colorectal liver metastases. Evidence is emerging that a lesser margin may provide equally acceptable outcomes, but a critical margin, below which recurrence is higher and survival poorer, has not been universally agreed. In a recent publication, we reported peri-operative morbidity and clear margin as the two independent prognostic factors. The aim of the current study was to further analyse the effect of the width of the surgical margin on patient survival to determine whether a margin of 1 mm is adequate. METHODS: Two hundred and sixty-one consecutive primary liver resections for colorectal metastases were analysed from 1992 to 2007. The resection margins were assessed by microscopic examination of paraffin sections. The initial analysis was performed on five groups according to the resection margins: involved margin, 0-1 mm, >1-<4 mm, 4-<10 mm and > or = 10 mm. Subsequent analysis was based on two groups: margin <1 mm and >1 mm. RESULTS: With a median follow-up of 4.7 years, the overall 5-year patient and disease-free survival were 38% and 22%, respectively. There was no significant difference in patient- or disease-free survival between the three groups with resection margins >1 mm. When a comparison was made between patients with resection margins < or = 1 mm and patients with resection margins >1 mm, there was a significant 5-year patient survival difference of 25% versus 43% (P < 0.04). However, the disease-free survival difference did not reach statistical significance (P = 0.14). CONCLUSIONS: In this cohort of patients, we have demonstrated that a resection margin of greater than 1 mm is associated with significantly improved 5-year overall survival, compared with involved margins or margins less than or equal to 1 mm. The possible beneficial effect of greater margins beyond 1 mm could not be demonstrated.

Poorer survival in patients whose explanted hepatocellular carcinoma (HCC) exceeds Milan or UCSF Criteria. An analysis of liver transplantation in HCC in Australia and New Zealand.

BACKGROUND: Milan and University of California San Francisco (UCSF) Criteria have been used for selection of patients with hepatocellular carcinoma (HCC) for liver transplantation (LTx). The aims of this study were to analyse the results of LTx for HCC in Australia and New Zealand with emphasis on the effects of discordance between pre-LTx radiological and post-LTx pathological staging. METHODS: A total of 186 LTx for HCC carried out between July 1985 and August 2003 were included. Patients were categorized according to the Milan and UCSF Criteria. RESULTS: The median follow-up was 6.55 years (range 2.96-20.93 years). Pre-LTx factors associated with better survival include tumour size < or = 5 cm, number of tumours < or = 3, staging within Milan and UCSF Criteria and more recent transplantation (1996-2003). In all, 14 patients had a pre-LTx stage outside the Milan but within the UCSF Criteria. One- and 5-year patient survival rates were, respectively, 88% and 74% within the Milan Criteria, and 87% and 73% within the UCSF Criteria. Vascular invasion, capsular invasion, lymph node invasion and pathological stage outside UCSF Criteria were associated with poor outcome. Of patients within the Milan and UCSF Criteria pre-LTx, 24% and 18%, respectively, were outside the same criteria post-LTx. These patients had poorer survival rates. CONCLUSIONS: The use of the UCSF Criteria in this cohort increased the number of patients eligible for LTx without compromising 5-year survival rates. Patients whose explant tumours were outside the Milan or UCSF Criteria had poorer outcomes compared with those whose explants remained within these criteria.