John W. C. Chen

Background/Objectives: Poor outcomes in liver cancer are often driven by late-stage diagnoses and high recurrence rates following surgical resection, highlighting a critical clinical need for non-invasive surveillance tools. This proof-of-concept study investigates the utility of circulating extracellular vesicles (EVs) to track dynamic molecular shifts and monitor patient response following tumour resection. Methods: Small ribonucleic acid (RNA) sequencing was conducted on matched tumour tissue, tissue-derived EVs, and plasma EVs collected at the time of surgery from patients with liver cancer. To capture longitudinal transcriptomic changes, plasma EVs were also collected at a post-operative follow-up appointment. Results: At the time of surgery, the transcriptomic profile of circulating plasma EVs strongly correlated with both the matched tumour tissue and tissue-derived EVs, exhibiting substantial transcript overlap. However, at post-operative follow-up, the circulating EV cargo significantly diverged from the primary tumour profile. This loss of similarity was characterised by a distinct shift in RNA cargo, including 173 uniquely detected transcripts absent at baseline. Conclusions: Circulating EVs accurately reflect the local hepatic transcriptome at the time of surgery, but their profile dynamically and fundamentally diverges once the tumour is removed. This post-surgical divergence provides an initial proof-of-concept that utilising patients as their own internal control to longitudinally profile EV cargo may track the clearance of tumour signals and monitor post-surgical systemic changes, highlighting their potential utility for future longitudinal studies aimed at tracking cancer progression and recurrence.

Background: Expansion in liver transplantation (LT) criteria for HCC from Milan to UCSF has not adversely impacted overall survival, prompting further expansion towards Metroticket 2.0 (MT2). In this study, we compared patient survival post-transplant before and after 2007 and long-term outcomes for LT within Milan versus UCSF criteria (to determine the true benefit of the expansion of criteria) and retrospectively validated the MT2 criteria. Methods: Retrospective analysis of ANZLITR (including all patients transplanted for HCC since July 1997). The entire cohort was divided based on criteria used at the time of listing, namely, Milan era (1997–2006) and the UCSF era (2007–July 2015). Results: The overall 5- and 10-year cumulative survival rates for the entire cohort of 691 patients were 78% and 69%, respectively. Patients transplanted in UCSF era had significantly higher 5- and 10-year survival rates than in the Milan era (80% vs. 73% and 72% vs. 65%, respectively; p = 0.016). In the UCSF era, the 5-year survival rate for patients transplanted within Milan criteria was significantly better than those transplanted outside Milan but within UCSF criteria (83% vs. 73%; p < 0.024). Patients transplanted within the MT2 criteria had a significantly better 5- and 10-year survival rate as compared to those outside the criteria (81% vs. 64% and 73% vs. 50%, respectively; p = 0.001). Conclusion: Overall survival following LT for HCC has significantly improved over time despite expanding criteria from Milan to UCSF. Patients fulfilling the MT2 criteria have a survival comparable to the UCSF cohort. Thus, expansion of criteria to MT2 is justifiable.

There is a growing disparity between the number of liver transplant (LT) candidates and availability of suitable liver allografts. Antibody-mediated rejection (AMR), secondary to positive donor-specific antibodies (DSA), remains a concern in liver transplantation. This study aimed to correlate expression of DSA on pre-transplant screening and outcomes of LT, specifically development of AMR in liver allografts and liver function profile in the post-operative period.

Pancreatic cancer (PC) has the worst survival of all periampullary cancers. This may relate to histopathological differences between pancreatic cancers and other periampullary cancers. Our aim was to examine the distribution and histopathologic features of pancreatic, ampullary, biliary and duodenal cancers resected with a pancreaticoduodenectomy (PD) and to examine local trends of periampullary cancers resected with a PD. A retrospective review of PD between January 2000 and December 2012 at a public metropolitan database was performed. The institutional ethics committee approved this study. There were 142 PDs during the study period, of which 70 cases were pre-2010 and 72 post-2010, corresponding to a recent increase in the number of cases. Of the 142 cases, 116 were for periampullary cancers. There were also proportionately more PD for PC (26/60, 43% pre-2010 vs 39/56, 70% post-2010, P = 0.005). There were 65/116 (56%) pancreatic, 29/116 (25%), ampullary, 17/116 (15%) biliary and 5/116 (4%) duodenal cancers. Nodal involvement occurred more frequently in PC (78%) compared to ampullary (59%), biliary (47%) and duodenal cancers (20%), P = 0.002. Perineural invasion was also more frequent in PC (74%) compared to ampullary (34%), biliary (59%) and duodenal cancers (20%), P = 0.002. Microvascular invasion was seen in 57% pancreatic, 38% ampullary, 41% biliary and 20% duodenal cancers, P = 0.222. Overall, clear margins (R0) were achieved in fewer PC 41/65 (63%) compared to ampullary 27/29 (93%; P = 0.003) and biliary cancers 16/17 (94%; P = 0.014). This study highlights that almost half of PD was performed for cancers other than PC, mainly ampullary and biliary cancers. The volume of PD has increased in recent years with an increased proportion being for PC. PC had higher rates of nodal and perineural invasion compared to ampullary, biliary and duodenal cancers.

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.

Abstract  Scorpion envenomation causes severe upper abdominal pain associated with nausea and vomiting. Although scorpion venom (SV) stimulates pancreatic and gastric secretion in animal models, its effects on duodenal and biliary motility have not been reported. The aim of this study was to determine the effects of SV on sphincter of Oddi (SO), duodenal and gall bladder motility and pancreatic amylase output. Anaesthetized Australian possums (n = 21) were infused with SV via intravenous or closed intra‐arterial routes. Blood pressure, SO, duodenal and gall bladder motility were continuously monitored for 4 h. Trans‐sphincteric flow (TSF), an indicator of bile duct resistance, was measured concurrently. The amylase output in pancreatic juice was also measured. SV infusion resulted in profound transient increase in blood pressure, SO motility and a significant decrease in TSF. No significant differences were noted in SO basal pressure changes. A transient increase in gall bladder tone, duodenal contraction amplitude and frequency, and amylase output were noted. Following the peak in blood pressure, amylase output, SO, gall bladder and duodenal motility were depressed. SV induces a rapid but transient increase in biliary and duodenal motility that is associated with stimulation of pancreatic amylase output. These changes may contribute to gastrointestinal symptoms associated with early phases of envenomation.