INTRODUCTION:Resection of primary tumor and liver metastases is the gold standard for colorectal cancer with liver-only metastases (CRLM). Although treatment options have expanded to enable conversion of unresectable to resectable CRLM, about 40% of patients will have definitively unresectable disease. Major advances in surgical techniques, immunosuppressive protocols and patient selection criteria for liver transplantation have resulted in improved outcomes. AREAS COVERED:A literature search has been conducted in Pubmed for articles published between 2014 and 2024. This review paper comments on current liver-directed treatment options for CRLM: resection, percutaneous ablation, conversion-chemotherapy, TACE, SIRT, and SABR. We explore evidence for liver transplantation in patients with unresectable CRLM, comment on possible limitations for implementation in clinical practice and give an overview of the current guidelines on liver transplantation in the USA, Europe, the United Kingdom, and Australia/New Zealand. EXPERT OPINION:The recent randomized TRANSMET trial, investigating liver transplantation versus chemotherapy in unresectable CRLM, shows promising 5-year OS reaching similar values as for other accepted liver transplantation indications. Further investigations with RCTs to investigate reproducibility and feasibility in clinical practice are needed. Before liver transplantation can be implemented as a standard treatment option, reorganizations at federal, regional and hospital levels would be required.

Background: Despite advances in surgical techniques and chemotherapy, poor outcomes persist in pancreatic malignancy. This study aimed to investigate clinical outcomes and describe the impact of factors like the closest resection margin on overall survival following open pancreatoduodenectomy at a tertiary referral centre over a ten-year period. Methods: Patients who underwent a pancreaticoduodenectomy at a tertiary hospital in South Australia between 2009-2019 were included in this retrospective study. Patient demographics, systemic treatments, complications, and histological features were analysed for their role in overall survival. Kaplan-Meier survival curves were used to assess patient survival and estimate median survival time. Results: There were 134 open pancreaticoduodenectomy procedures during 2009-2019. Majority of patients were male (54.7%) between 65-75 years of age (41%) with an ASA physical status classification grade of 3 (63.3%). 56.7% of patients experienced a complication with 5 in-hospital deaths recorded and 12 ISPGF grade B or C pancreatic anastomotic leaks (n=5, n=7 respectively). 88% of resected specimens were malignant with an overall 5-year survival of 32%. A resection margin of >2 mm had a significantly improved overall survival compared to 0 mm (p=0.01). There was no survival benefit for a resection margin of <1 mm or 1-2 mm compared 0mm margin (p=0.6 and p=0.2 respectively). 65 patients (54.6%) experienced either local or distal disease recurrence by the end of the study period. Conclusions: There has been no improvement in overall survival post pancreatoduodenectomy for pancreatic malignancy. Further research into the clinical significance of the R status classification is required.

The study used the American Time Use Survey data from 2010 to 2019 to compare the daily moderate-to-vigorous activity of Native Hawaiians and Pacific Islanders (NHPI) and seven Asian ethnic subgroups. Adults aged 24 years and older were included. The study analyzed activities from sports and recreation, household activities, and all activities carried out during the day. Outcomes were determined by the completion of 30 min or more of moderate-to-vigorous activity and the type of activity carried out in the day. Significant ethnic differences were observed for sports and recreation but not for household activities and not for all activities carried out during the day. Of the ethnic populations, NHPI were the least active, and Asian Indians and Chinese were the most active. A majority achieved 30 min or more of moderate-to-vigorous activity during the day from all their activities. Physical activity from household activities exceeded physical activity from sports and recreation. The most physically active group was adults over the age of 65 years, perhaps reflecting more time to exercise or greater concerns about their health. For sports and recreation, exercising with someone doubled the minutes of moderate-to-vigorous activity. The results emphasize the importance of activities performed around the household in addition to sports and recreation and the benefit of exercising with someone. Ethnic populations may be receptive to interventions that emphasize activities they are performing in their daily lives.

This study examined differences in poverty and health among Native Hawaiians and Pacific Islanders (NHPI) and 6 disaggregated Asian ethnic subgroups and an aggregated Other Asian category. Participants were followed longitudinally for 2 years using data from 2009 to 2019 from the Current Population Survey, a monthly survey conducted by the Census Bureau. Having 2 years of data enabled the study to assess both prevalence of poverty and fair/poor health in only 1 of the 2 years and in both years. For NHPI, 13.5% were in poverty 1of the 2 years and 7.1% in both years. Asian ethnicities showed high variability ranging from a low of 6.4% for 1 year and 1.9% for 2 years among Asian Indians to 16.0% for 1 year and 6.3% for 2 years among Vietnamese. Fair/poor health also showed ethnic variability, made most apparent after age-sex adjustment in regression models. For poverty, after adjustment, Asian Indians, Filipinos and Japanese had significantly lower odds of being in poverty at least 1 year than NHPI. For having fair/poor health, Asian Indians and Japanese experienced lower odds than NHPI for both 1 and 2 years and Filipinos for 1 year, after age/sex adjustment. The results emphasize the diversity of Asian and Pacific Islander populations, the variability of poverty over time, and the importance of using disaggregated data to understand ethnic differences in poverty and health. These findings can be used to inform future modeling of social determinants on poverty and health among NHPI and Asian subgroups.

Australian Islet Transplant Consortium. Introduction: Total Pancreatectomy and Islet-Auto Transplant (TPIAT) is only available in two locations in Australia at present. TPIAT is currently offered in South Australia for patients with confirmed chronic and hereditary pancreatitis however relies on remote isolation 730km away, causing extended cold ischemic time. This study aims to illustrate patients’ outcomes until 12 months post TPIAT surgery with lengthened ischemic times.Method: This is a retrospective cohort analysis of 10 of 11 patients who underwent TPIAT for Chronic Pancreatitis from 2015 to 2020. Metabolic outcomes, c-peptide, glycated haemoglobin (HbA1c), insulin requirement and analgesia requirement are observed at baseline, 3-, 6- and 12-months post-surgery compared with cold ischemia times, islet equivalent counts and islet equivalents per kilogram of body weight. Results: Of the 11-patient cohort, patients who had bloods at 12 months post, all show detectable c-peptide ranging from 0.05 to 0.89nmol/L. The median HbA1c is at 12 months 6.6%. Insulin Independence was observed in 50% of patients. Nil analgesia requirements were observed in 60% of patients. 1 recipient died 3 days post TPIAT due to cardiac complications, and refusal of blood product transfusions due to religious reasons. The median islet equivalent per kilogram of body weight was 5276 ranged from 1130 to 11665 with a median total ischemic time 11:52hrs from pancreatectomy to transplant.Conclusion: Despite the pancreas needing to be shipped by air for Islet Isolation interstate, South Australia’s TPIAT program has demonstrated to be a successful treatment for chronic pancreatitis improving quality life shown by significant reduction in narcotic dependence, insulin independence and stable glycaemia control. Kidney, Transplant & Diabetes Research Australia. References: 1. Collaborative Islet Transplant Registry

This study used the American Time Use Survey (ATUS) to examine socialization, relaxation, and leisure activities throughout the day as related to social determinants of health (SDOH). The study population was adults aged 25 years and older who participated in the ATUS in 2014–2016, the most recent years for collecting SDOH. Descriptive analyses provide characteristics of the study population. Graphical analyses display socialization by SDOH across the hours of the day based on adjusted regression models. Quasi-binomial models analyzed the association between the numbers of minutes of various activities and SDOH. Associations between SDOH and sleeplessness (yes or no) were explored using logistic regression. For much of the day, being female, having less education, living in poverty, and having food insecurity were associated with more time socializing and relaxing. The major activities under socializing and relaxation are watching television and movies. Having a college degree was strongly associated with increased minutes of sports activity, whereas living in poverty and food insecurity were associated with fewer minutes. Less education, living in poverty, and having food insecurity were associated with sleeplessness. A possible mechanism of the effects of SODH on health is by its altering of the patterns of daily life.

Patients with high model for end-stage liver disease (MELD) scores waiting for liver transplantation in Australia and New Zealand (ANZ) have had limited access to deceased donor livers and therefore binational sharing of livers, for patients with a MELD score >= 35 was introduced in February 2016. Waiting list mortality, post-transplant outcomes and intention-to-treat survival were compared between patients whose MELD score reached 35 on the waiting list between October 2013 and April 2015 (Pre-Share 35 group, n = 23) and patients who were Share 35 listed between February 2016 and May 2022 (Share 35 group, n = 112). There was significantly reduced waiting list mortality in share 35 listed patients in comparison to the pre-Share 35 group (11.7% vs. 52.2%, OR .120 95% CI .044-.328, P < .001). Post-transplant patient and graft survival were not significantly different between the groups (5-year patient survival 82% vs. 84%, P = .991, 5-year graft survival 82% vs. 76%, P = .543). Intention-to-treat survival was superior in the Share 35 group (HR .302, 95% CI .149-.614, P < .001). Introduction of Share 35 in ANZ resulted in a 78% risk reduction in waiting list mortality, equivalent post-transplant survival and an improvement in intention-to-treat survival.

Background and aims: Homozygous familial hypercholesterolaemia (FH) causes severe cardiovascular disease from childhood. Conventional drug therapy is usually ineffective; lipoprotein apheresis (LA) is often required. Liver transplantation (LT) can correct the metabolic defect but is considered a treatment of last resort. Newer drugs including lomitapide and evinacumab might reduce the need for apheresis and LT. We sought to determine the long-term outcomes following LT in Australia and New Zealand.Methods: We analysed demographic, biochemical and clinical data from all patients in Australia and New Zealand who have received LT for homozygous FH, identified from the Australia and New Zealand Liver and Intestinal Transplant Registry.Results: Nine patients (five female; one deceased; seven aged between 3 and 6 years at the time of LT and two aged 22 and 26 years) were identified. Mean follow-up was 14.1 years (range 4-27). Baseline LDL-cholesterol off all treatment was 23 +/- 4.1 mmol/L. Mean LDL-cholesterol on medical therapy (including maximal statin therapy in all patients, ezetimibe in three and LA in five) was 11 +/- 5.7 mmol/L (p < 0.001). After LT, mean LDL-cholesterol was 2.6 +/- 0.9 mmol/L (p = 0.004) with three patients remaining on statin therapy and none on LA. One patient died from acute myocardial infarction (AMI) three years after LT. Two patients required aortic valve replacement, more than 10 years after LT. The remaining six patients were asymptomatic after eight to 21 years of follow-up. No significant adverse events associated with immunosuppression were reported.Conclusions: LT for homozygous FH was highly effective in achieving substantial long-term reduction in LDL-cholesterol concentrations in all nine patients. LT re-mains an option for severe cases of homozygous FH where drug therapy combined with apheresis is ineffective or unfeasible.

The Australian Islet Consortium. Introduction: It is now well known and published TPIAT is effective as a treatment option for hereditary pancreatitis (HP), and it does improve quality of life for affected patients, hence accessibility should be maintained for all Australians. We undertook a financial audit of the costings of TPIAT in Australia. Method: The initial stage was the collection of data surrounding the 15 patients who have undergone TPIAT in South Australia during the 6-year time period of 2017 til-now (April 2023). Data collected included the number of acute pancreatitis episodes leading to presentations to tertiary hospitals per year prior to TPIAT surgery, the medications required pre-TPIAT, the number of nights requiring Intensive Care (ICU) post-TPIAT, the incidence of complications and/or ‘return to theatre’ occurring during or post-TPIAT surgery, the overall length of admission, the incidence of re-admission, and medications required post-TPIAT surgery. Results: Average costs of TPIAT of $204 438.63 Australian Dollars ($136 830.78 US Dollars), ranged to mean average cost of $352 052.72 ($235 742.22 US Dollars), to a least optimal cost of $494 119.21 ($330 873.05 US Dollars). The ongoing yearly expense of care post-TPIAT was $2939.86 ($1968.19 US Dollars). The optimal costing of traditional medical management, without stenting of the pancreatic duct, was $123 136.38 ($82 454.82 US Dollars). The mean average costing of traditional medical management was estimated to be $619 526.64 per year ($414 848.62 US Dollars), and the least optimal costing of traditional medical management was $949 679.53 ($635 926.24 US Dollars). The complications of HP are estimated to cost $8239.53 per year ($5517.37 US Dollars), and the expense of a two-year treatment of pancreatic cancer is estimated to be $32 816.52 ($21 974.66). The conversion of Australian dollars to US dollars was based on the conversion $1 AUD to $0.67 USD as at the 4th May 2023. Conclusion: This audit has illustrated the economic value of TPIAT surgery in the treatment of severe HP in Australia’s healthcare system. TPIAT expense ranging from $200000 to $500000 compared with up to just below one million Australian dollars for traditional medical management. The comparative annual expense post-TPIAT under $3000 against yearly expense of over $8000 for traditional medical management for those who do not have TPIAT surgery for their severe disease. This information should be very useful for upcoming review and indexation of Australia’s Medicare system. Kidney, Transplant and Diabetes Research Australia (KTDRA). References: 1. SA Health

The primary objective was to learn the extent that muscle function, mobility, and self-reported health decline following incident diabetes, stroke, lung problem, and heart problems. A secondary objective was to measure subsequent recovery following the incident events. A longitudinal panel study of the natural history of four major chronic diseases using the Health and Retirement Study, a nationally representative sample of adults over age 50 years. People first interviewed from 1998-2004 were followed across five biannual exams. The study included 5,665 participants who reported not having diabetes, stroke, lung problems, and heart problems at their baseline interview. Their mean age was 57.3 years (SD = 6.0). They were followed for an average of 4.3 biannual interviews. Declines and subsequent recovery in self-reported health, muscle function, and mobility were examined graphically and modeled using negative binomial regression. The study also measured the incidence rates and prevalence of single and multiple chronic diseases across the follow-up years.Self-reported health and muscle function declined significantly following incident stroke, heart problems, lung problems, and multiple chronic diseases. Mobility declined significantly except following incident diabetes. Self-reported health improved following incident multiple chronic conditions, but recovery was limited compared to initial decline. Population prevalence after five follow-up waves reached 9.0% for diabetes, 8.1% for heart problems, 3.4% for lung disease, 2.1% for stroke, and 5.2% for multiple chronic diseases. Significant declines in self-reported health, muscle function, and mobility occurred within two years of chronic disease incidence with only limited subsequent recovery. Incurring a second chronic disease further increased the declines. Early intervention following incident chronic disease seems warranted to prevent declines in strength, mobility, and perceptions of health.

Background. Prevalence of concurrent liver diseases among liver transplant recipients and impact on posttransplant outcomes are unknown. Methods. This retrospective study included adult liver transplants between January 1‚ 1985‚ and December 31‚ 2019‚ from the Australian and New Zealand Liver and Intestinal Transplant Registry. Up to 4 liver disease causes were recorded for each transplant; concurrent liver diseases were defined as >1 liver disease indication for transplantation, excluding hepatocellular carcinoma. Impact on posttransplant survival was determined using Cox regression. Results. A total of 840 (15%) of 5101 adult liver transplant recipients had concurrent liver diseases. Recipients with concurrent liver diseases were more likely male (78% versus 64%) and older (mean age 52 versus 50 y). A higher proportion of liver transplants for hepatitis B (12% versus 6%), hepatitis C (33% versus 20%), alcohol liver disease (23% versus 13%), and metabolic-associated fatty liver disease (11% versus 8%, all P < 0.001) were identified when all indications were included than with primary diagnosis only. The number and proportion of liver transplants performed for concurrent liver diseases have increased from 8 (6%) during Era 1 (1985–1989) to 302 (20%) during Era 7 (2015–2019; P < 0.001). Concurrent liver diseases were not associated with increased posttransplant mortality (adjusted hazard ratio, 0.98, 95% confidence interval, 0.84-1.14). Conclusions. Concurrent liver diseases are increasing among adult liver transplant recipients in Australia and New Zealand; however, they do not appear to impact posttransplant survival. Reporting all liver disease causes in the transplant registry reports provides more accurate estimates of liver disease burden.

Objective To assess longitudinal, population-based data on the prevalence and impact of chronic pancreatitis in children. Study design Administrative data linkage was used to ascertain an index cohort consisting of all individuals who had an initial diagnosis of chronic pancreatitis before age 19 years in the South Australian public hospital system between June 2000 and June 2019. Age- and sex-matched controls were drawn from the general population of South Australia, children with type 1 diabetes, and children with type 2 diabetes. Main outcomes and measures included hospital visits, days in hospital, emergency department (ED) visits, intensive care unit (ICU) admissions, education comparators, and incidence and prevalence estimates. Results A total of 73 incident cases were identified. The crude prevalence and incidence of pediatric chronic pancreatitis were estimated at 6.8/100 000 and 0.98/100 000 per year, respectively. Of the index cohort, 24 cases (32.8%) of pediatric chronic pancreatitis were identified as occurring in children of Aboriginal and/or Torres Strait Islander descent. Compared with matched general population controls, children with chronic pancreatitis averaged 11-fold more hospital visits, 5-fold more ED visits, and 9-fold more ICU admissions; spent 10-fold more days in the hospital; and had a 2-fold higher rate of absence from school (P < .001 for all). Similarly, children with chronic pancreatitis used substantially more health resources than children with type 1 or 2 diabetes. Conclusions Pediatric patients with chronic pancreatitis consume a high volume of public health services and are significantly impacted in their ability to engage in education.

The prognostic role of cardiac dysfunction in cirrhotic patients is increasingly recognized. We studied its impact on morbidity and mortality before and after liver transplantation (LT) including development of post-transplant cardiovascular disease (CVD). In this retrospective study, cirrhotic patients who underwent LT assessment from January 2010 to December 2020 were reviewed. Demographics, cardiac investigations and clinical courses were analyzed to identify the prevalence of cardiac dysfunction and its role in LT outcomes. Survival analysis was performed using Cox proportional hazard regression modelling, with LT as a time-varying covariate and as an interaction variable with cardiac dysfunction. Three hundred and eight patients (70% male) were studied. The median (interquartile range) age at LT assessment was 56 (12) years. Cardiac dysfunction was found in 178 (58%) patients (diastolic, 169; systolic, 26; both, 17) and was significantly associated with hepatorenal syndrome/acute kidney injury and peri- and post-transplant morbidity (adjusted odds ratio [aOR] 1.94, 95% CI 1.06-3.52, P < .001; aOR 2.01, 95% CI 1.06-3.82, P = .033; aOR 1.9, 95% CI 1.01-3.65, P = .023, respectively). Cardiac dysfunction was not associated with mortality before (adjusted hazard ratio [aHR] 1.01, 95% CI .99-1.01) or after LT (aHR .74, 95% CI .4-1.05. Post-transplant CVD (61% cardiac failure) occurred in 36 patients, and there was no significant association with cardiac dysfunction (P = .11). Cardiac dysfunction was common in LT candidates and was significantly associated with morbidity before and after LT. Studies on the role of advanced echocardiographic parameters to improve diagnosis of cardiac dysfunction and optimize LT outcomes are needed.

Background Interventions to support patients with complex needs have proliferated in recent years, but the question of how to identify patients with complex needs has received relatively little attention. There are innumerable ways to structure inclusion and exclusion criteria for complex care interventions, and little is known about the implications of choices made in designing patient selection criteria. Objective To provide insights into the design of patient selection criteria for interventions, by implementing criteria sets within a large health plan member population and comparing the characteristics of the resulting complex patient cohorts. Design Retrospective observational descriptive study. Subjects Patients identified as having complex needs, within the membership population of Kaiser Permanente Southern California, a large, population-based health plan with more than 4 million members. We characterize five commonly used archetypes of complex needs: high-cost patients, patients with multiple chronic conditions, frail elders, emergency department high-utilizers, and inpatient high-utilizers. Measures We selected an initial set of criteria for identifying patients in each of the archetypical complex populations, based on available administrative data. We then tested multiple variants of each definition. We compared the resulting patient cohorts using univariate and bivariate descriptive statistics. Key Results Overall, 32.7% of the 3,112,797 adults in our population-based sample were selected by at least one of the 25 definitions of complexity we tested. Across definitions the total number of patients identified as complex ranged from 622,560 to 1583 and complex patient cohorts varied widely in demographic characteristics, chronic conditions, healthcare utilization, spending, and survival. Conclusions Choice of patient population is critical to the design of complex care programs. Exploratory analyses of population criteria can provide useful information for program planning in the setting of limited resources for interventions. Data such as these should be generated as a key step in program design.