Liver specification of human iPSC-derived endothelial cells transplanted into mouse liver.

Background & Aims: Liver sinusoidal endothelial cells (LSECs) are important in liver development, regeneration, and pathophysiology, but the differentiation process underlying their tissue-specific phenotype is poorly understood and difficult to study because primary human cells are scarce. The aim of this study was to use human induced pluripotent stem cell (hiPSC)-derived LSEC-like cells to investigate the differentiation process of LSECs. Methods: hiPSC-derived endothelial cells (iECs) were transplanted into the livers of Fah-/-/Rag2-/-/Il2rg-/- mice and assessed over a 12-week period. Lineage tracing, immunofluorescence, flow cytometry, plasma human factor VIII measurement, and bulk and single cell transcriptomic analysis were used to assess the molecular and functional changes that occurred following transplantation. Results: Progressive and long-term repopulation of the liver vasculature occurred as iECs expanded along the sinusoids between hepatocytes and increasingly produced human factor VIII, indicating differentiation into LSEC-like cells. To chart the developmental profile associated with LSEC specification, the bulk transcriptomes of transplanted cells between 1 and 12 weeks after transplantation were compared against primary human adult LSECs. This demonstrated a chronological increase in LSEC markers, LSEC differentiation pathways, and zonation. Bulk transcriptome analysis suggested that the transcription factors NOTCH1, GATA4, and FOS have a central role in LSEC specification, interacting with a network of 27 transcription factors. Novel markers associated with this process included EMCN and CLEC14A. Additionally, single cell transcriptomic analysis demonstrated that transplanted iECs at 4 weeks contained zonal subpopulations with a region-specific phenotype. Conclusions: Collectively, this study confirms that hiPSCs can adopt LSEC-like features and provides insight into LSEC specification. This humanised xenograft system can be applied to further interrogate LSEC developmental biology and pathophysiology, bypassing current logistical obstacles associated with primary human LSECs. Impact and implications: Liver sinusoidal endothelial cells (LSECs) are important cells for liver biology, but better model systems are required to study them. We present a pluripotent stem cell xenografting model that produces human LSEC-like cells. A detailed and longitudinal transcriptomic analysis of the development of LSEC-like cells is included, which will guide future studies to interrogate LSEC biology and produce LSEC-like cells that could be used for regenerative medicine.

Early onset pancreatic cancer-exploring contemporary treatment and outcomes using real-world data.

BACKGROUND: Pancreatic cancer incidence is increasing in younger populations. Differences between early onset pancreatic cancer (EOPC) and later onset pancreatic cancer (LOPC), and how these should inform management warrant exploration in the contemporary setting. METHODS: A prospectively collected multi-site dataset on consecutive pancreatic adenocarcinoma patients was interrogated. Patient, tumour, treatment, and outcome data were extracted for EOPC (≤50 years old) vs LOPC (>50 years old). RESULTS: Of 1683 patients diagnosed between 2016 and 2022, 112 (6.7%) were EOPC. EOPC more frequently had the tail of pancreas tumours, earlier stage disease, surgical resection, and trended towards increased receipt of chemotherapy in the curative setting compared to LOPC. EOPC more frequently received 1st line chemotherapy, 2nd line chemotherapy, and chemoradiotherapy than LOPC in the palliative setting. Recurrence-free survival was improved for the tail of pancreas EOPC vs LOPC in the resected setting; overall survival was superior for EOPC compared to LOPC across the resected, locally advanced unresectable and metastatic settings. CONCLUSIONS: EOPC remains a small proportion of pancreatic cancer diagnoses. The more favourable outcomes in EOPC suggest these younger patients are overall deriving benefits from increased treatment in the curative setting and increased therapy in the palliative setting.

Are the screening guidelines for branch duct intraductal papillary mucinous neoplasms cost-effective in an Australian setting?

BACKGROUNDS: Intraductal papillary mucinous neoplasms (IPMN) are cystic neoplasms of the pancreatic ductal system. These incidental cystic lesions are increasingly found on radiological imaging and screened for malignant transformation. The Fukuoka consensus guidelines recommend screening with computed tomography, magnetic resonance imaging or endoscopic ultrasound. Branch duct IPMN (BD-IPMN) have significantly lower malignancy and mortality rates compared to main duct IPMN. Our aim was to assess the cost-effectiveness of guideline's recommendations for BD-IPMN screening of cysts between 2 and 3 cm in an Australian context. METHODS: Markov model decision analysis was used to calculate the incremental cost-effectiveness ratio (ICER) of screening. The ICER was compared to a willingness to pay (WTP) threshold of $50 000. We performed scenario analysis to examine the effect of cyst size and non-linearity of malignancy rate on ICER. Probabilistic sensitivity analyses (PSA) were performed on our input parameters. RESULTS: Screening resulted in 586 quality adjusted life years gained and a net present value of $20 379 939, resulting in a base-case ICER of $34 758. After scenario analysis for non-linearity of malignancy rate the ICER increases to $64 555, which is above the WTP threshold. PSA indicates that ICER is most susceptible to the pre-test malignancy rate. CONCLUSION: This cost analysis demonstrates that screening of 2-3 cm BD-IPMN according to current guidelines is unlikely to be cost-effective in an Australian context. To determine the true ICER, a cost analysis on real-world data is required.

Use and outcomes from neoadjuvant chemotherapy in borderline resectable pancreatic ductal adenocarcinoma in an Australasian population.

BACKGROUND: Use of neoadjuvant (NA) chemotherapy is recommended when pancreatic ductal adenocarcinoma (PDAC) is borderline resectable METHOD: A retrospective analysis of consecutive patients with localized PDAC between January 2016 and March 2019 within the Australasian Pancreatic Cancer Registry (PURPLE, Pancreatic cancer: Understanding Routine Practice and Lifting End results) was performed. Clinicopathological characteristics, treatment, and outcome were analyzed. Overall survival (OS) comparison was performed using log-rank model and Kaplan-Meier analysis. RESULTS: The PURPLE database included 754 cases with localised PDAC, including 148 (20%) cases with borderline resectable pancreatic cancer (BRPC). Of the 148 BRPC patients, 44 (30%) underwent immediate surgery, 80 (54%) received NA chemotherapy, and 24 (16%) were inoperable. The median age of NA therapy patients was 63 years and FOLFIRINOX (53%) was more often used as NA therapy than gemcitabine/nab-paclitaxel (31%). Patients who received FOLFIRINOX were younger than those who received gemcitabine/nab-paclitaxel (60 years vs. 67 years, p = .01). Surgery was performed in 54% (43 of 80) of BRPC patients receiving NA chemotherapy, with 53% (16 of 30) achieving R0 resections. BRPC patients undergoing surgery had a median OS of 30 months, and 38% (9 of 24) achieved R0 resection. NA chemotherapy patients had a median OS of 20 months, improving to 24 months versus 10 months for patients receiving FOLFIRINOX compared to gemcitabine/nab-paclitaxel (Hazard Ratio (HR) .3, p < .0001). CONCLUSIONS: NA chemotherapy use in BRPC is increasing in Australia. One half of patients receiving NA chemotherapy proceed to curative resection, with 53% achieving R0 resections. Patients receiving Infusional 5-flurouracil, Irinotecan and Oxaliplatin (FOLIRINOX) had increased survival than gemcitabine/nab-paclitaxel. Treatment strategies are being explored in the MASTERPLAN and DYNAMIC-Pancreas trials.

A novel high-throughput sequencing approach reveals the presence of a new virus infecting Rosa: rosa ilarvirus-1 (RIV-1).

Roses are one of the most valuable ornamental flowering shrubs grown worldwide. Despite the widespread of rose viruses and their impact on cultivation, they have not been studied in detail in the United Kingdom (UK) since the 1980's. As part of a survey of rose viruses entering the UK, 35 samples were collected at Heathrow Airport (London, UK) and were tested by RT-qPCR for different common rose viruses. Of the 35 samples tested using RT-qPCR for prunus necrotic ringspot virus (PNRSV; genus Ilarvirus), 10 were positive. Confirmatory testing was performed using RT-PCR with both PNRSV-specific and ilarvirus-generic primers, and diverse results were obtained: One sample was exclusively positive when using the ilarvirus-generic primers, and subsequent sequencing of the RT-PCR product revealed homology to other ilarviruses but not PNRSV. Further work to characterise the virus was performed using high throughput sequencing, both the MinION Flongle and Illumina MiSeq. The sequencing confirmed the presence of a new virus within group 2 of the genus Ilarvirus and we propose the name "rosa ilarvirus-1″ (RIV-1). Here, we describe the identification of a novel virus using the low-cost Flongle flow cell and discuss its potential as a front-line diagnostic tool.

Metal stents are safe and cost-effective for preoperative biliary drainage in resectable pancreaticobiliary tumours.

BACKGROUNDS: To compare the complication rates and overall costs of self-expandable metal stents (SEMS) and plastic stents (PS) in clinically indicated preoperative biliary drainage (PBD) prior to a pancreatoduodenectomy (PD). METHODS: We conducted an Australian multicentre retrospective cohort study using the databases of four tertiary hospitals. Adult patients who underwent clinically indicated endoscopic PBD prior to PD from 2010 to 2019 were included. Rates of complications attributable to PBD, surgical complications and pre-operative endoscopic re-intervention were calculated. Costing data were retrieved from our Financial department. RESULTS: Among the 157 included patients (mean age 66.6 ± 9.8 years, 45.2% male), 49 (31.2%) received SEMS and 108 received PS (68.8%). Baseline bilirubin was 187.5 ± 122.6 µmol/L. Resection histopathology showed mainly adenocarcinoma (93.0%). Overall SEMS was associated less complications (12.2% vs. 28.7%, p = 0.02) and a lower pre-operative endoscopic re-intervention rate (4.3 vs. 20.8%, p = 0.03) compared with PS. There was no difference in post-PD complication rates. On multivariate logistic regression analysis, stent type was an independent risk factor of PBD complication (OR of SEMS compared to PS 0.24, 95% CI 0.07-0.79, p = 0.02) but not for any secondary outcome measures. Upfront material costs were $56USD for PS and $1991USD for SEMS. Accounting for rates of complications, average costs were similar ($3110USD for PS and $3026USD for SEMS). CONCLUSION: In resectable pancreaticobiliary tumours, SEMS for PBD was associated with reduced risk of overall PBD-related complications and pre-surgical endoscopic reintervention rates and was comparable to PS in terms of overall cost.

Potato Virus Y Biological Strain Group YD: Hypersensitive Resistance Genes Elicited and Phylogenetic Placement.

Potato virus Y (PVY) disrupts healthy seed potato production and causes tuber yield and quality losses globally. Its subdivisions consist of strain groups defined by potato hypersensitive resistance (HR) genes and whether necrosis occurs in tobacco, and phylogroups defined by sequencing. When PVY isolate PP was inoculated to potato cultivar differentials with HR genes, the HR phenotype pattern obtained resembled that caused by strain group PVYD isolate KIP1. A complete genome of isolate PP was obtained by high-throughput sequencing. After removal of its short terminal recombinant segment, it was subjected to phylogenetic analysis together with 30 complete nonrecombinant PVY genomes. It fitted within the same minor phylogroup PVYO3 subclade as KIP1. Putative HR gene Nd was proposed previously to explain the unique HR phenotype pattern that developed when differential cultivars were inoculated with PVYD. However, an alternative explanation was that PVYD elicits HR with HR genes Nc and Ny instead. To establish which gene(s) it elicits, isolates KIP1 and PP were inoculated to F1 potato seedlings from (i) crossing 'Kipfler' and 'White Rose' with 'Ruby Lou' and (ii) self-pollinated 'Desiree' and 'Ruby Lou', where 'Kipfler' is susceptible (S) but 'White Rose', 'Desiree', and 'Ruby Lou' develop HR. With both isolates, the HR:S segregation ratios obtained fitted 5:1 for 'Kipfler' × 'Ruby Lou', 11:1 for 'White Rose' × 'Ruby Lou', and 3:1 for 'Desiree'. Those for 'Ruby Lou' were 68:1 (isolate PP) and 52:0 (isolate KIP1). Because potato is tetraploid, these ratios suggest PVYD elicits HR with Ny from 'Ruby Lou' (duplex condition) and 'Desiree' (simplex condition) and Nc from 'White Rose' (simplex condition) but provide no evidence that Nd exists. Therefore, our differential cultivar inoculations and inheritance studies highlight that PVYD isolates elicit an HR phenotype in potato cultivars with either of two HR genes Nc or Ny, so putative gene Nd can be discounted. Moreover, phylogenetic analysis placed isolate PP within the same minor phylogroup PVYO3 subclade as KIP1, which constitutes the most basal divergence within overall major phylogroup PVYO.

Circulating tumor DNA dynamics and recurrence risk in patients undergoing curative intent resection of colorectal cancer liver metastases: A prospective cohort study.

BACKGROUND: In patients with resectable colorectal liver metastases (CRLM), the role of pre- and postoperative systemic therapy continues to be debated. Previous studies have shown that circulating tumor DNA (ctDNA) analysis, as a marker of minimal residual disease, is a powerful prognostic factor in patients with nonmetastatic colorectal cancer (CRC). Serial analysis of ctDNA in patients with resectable CRLM could inform the optimal use of perioperative chemotherapy. Here, we performed a validation study to confirm the prognostic impact of postoperative ctDNA in resectable CRLM observed in a previous discovery study. METHODS AND FINDINGS: We prospectively collected plasma samples from patients with resectable CRLM, including presurgical and postsurgical samples, serial samples during any pre- or postoperative chemotherapy, and serial samples in follow-up. Via targeted sequencing of 15 genes commonly mutated in CRC, we identified at least 1 somatic mutation in each patient's tumor. We then designed a personalized assay to assess 1 mutation in plasma samples using the Safe-SeqS assay. A total of 380 plasma samples from 54 patients recruited from July 2011 to Dec 2014 were included in our analysis. Twenty-three (43%) patients received neoadjuvant chemotherapy, and 42 patients (78%) received adjuvant chemotherapy after surgery. Median follow-up was 51 months (interquartile range, 31 to 60 months). At least 1 somatic mutation was identified in all patients' tumor tissue. ctDNA was detectable in 46/54 (85%) patients prior to any treatment and 12/49 (24%) patients after surgery. There was a median 40.93-fold (19.10 to 87.73, P < 0.001) decrease in ctDNA mutant allele fraction with neoadjuvant chemotherapy, but ctDNA clearance during neoadjuvant chemotherapy was not associated with a better recurrence-free survival (RFS). Patients with detectable postoperative ctDNA experienced a significantly lower RFS (HR 6.3; 95% CI 2.58 to 15.2; P < 0.001) and overall survival (HR 4.2; 95% CI 1.5 to 11.8; P < 0.001) compared to patients with undetectable ctDNA. For the 11 patients with detectable postoperative ctDNA who had serial ctDNA sampling during adjuvant chemotherapy, ctDNA clearance was observed in 3 patients, 2 of whom remained disease-free. All 8 patients with persistently detectable ctDNA after adjuvant chemotherapy have recurred. End-of-treatment (surgery +/- adjuvant chemotherapy) ctDNA detection was associated with a 5-year RFS of 0% compared to 75.6% for patients with an undetectable end-of-treatment ctDNA (HR 14.9; 95% CI 4.94 to 44.7; P < 0.001). Key limitations of the study include the small sample size and the potential for false-positive findings with multiple hypothesis testing. CONCLUSIONS: We confirmed the prognostic impact of postsurgery and posttreatment ctDNA in patients with resected CRLM. The potential utility of serial ctDNA analysis during adjuvant chemotherapy as an early marker of treatment efficacy was also demonstrated. Further studies are required to define how to optimally integrate ctDNA analyses into decision-making regarding the use and timing of adjuvant therapy for resectable CRLM. TRIAL REGISTRATION: ACTRN12612000345886.

Should bariatric surgery be offered for hepatocellular adenomas in obese patients?

BACKGROUND: Obesity and metabolic syndrome are increasingly recognized as risk factors for development of hepatocellular adenoma (HCA). The implications of weight loss on HCA regression has not been previously reviewed. OBJECTIVES: To analyze the effects of surgical and nonsurgical weight loss on HCA. SETTING: University Tertiary Hospital. METHODS: Literature review of full-text articles from PubMed and Scopus on patients with HCA who underwent surgical or nonsurgical weight loss was performed. Only English language articles were included and editorial comments were excluded. Wilcoxon signed rank test was used for paired data analysis. Spearman correlation was used for correlation between percent excess weight loss (%EWL) and number and size of HCA lesions. RESULTS: Out of 4 studies, 7 patients were included in this review, all of whom were female. The median preintervention body mass index was 41 kg/m2 compared with the postintervention body mass index of 28 kg/m2 (P = .002). The %EWL following intervention positively correlated to reduction in number of HCA lesions (%) postintervention, with a Spearman correlation of .78 (P = .04). Similarly, %EWL postintervention was positively correlated, though not statistically significant, to reduction in lesion size (%), with a Spearman correlation of .46 (P = .29). All patients who were candidates for liver resection preintervention based on lesion size > 5 cm avoided liver resection postintervention following surgical and nonsurgical weight loss. CONCLUSIONS: Effective long-term weight loss by surgical and nonsurgical methods result in regression of HCAs. Weight loss could avoid major liver resections or decrease the morbidity associated with liver surgery. Bariatric surgery should be considered as an option for management of surgically challenging HCAs in carefully selected obese patients. Multicenter long-term trials, while adjusting for cofounding factors, are required to determine the effects of surgical compared with nonsurgical weight loss on maintenance of HCA regression.

The incidence of symptomatic remnant gall bladder: a population study.

BACKGROUND: Subtotal cholecystectomy is utilized in conditions of high risk to critical structures, like the common bile duct. However, the remnant gall bladder may become symptomatic and require a completion cholecystectomy for treatment. This second procedure can itself be a risk to critical structures. To establish the incidence of redo-cholecystectomy and identify risk factors that lead to subtotal cholecystectomy and repeat operation in a review of state-based practices for cholecystectomy. METHODS: A search of state coding records relating to cholecystectomy from 1998 to 2016. Patients who were coded for cholecystectomy-related procedures on different dates were identified. Patients who underwent the procedures within 6 months were excluded to avoid acute post-operative complications and gall bladder malignancy. RESULTS: 210 719 cholecystectomies were performed. 1133 required repeat procedure. 616 were excluded, leaving 516 (0.25%) cholecystectomy patients requiring a second cholecystectomy. The subsequent operation was more likely to be an emergency procedure; involve transcystic bile duct exploration, adhesiolysis and require intensive care unit admission post-operatively. A repeat cholecystectomy was more likely to occur after having the primary procedure at a public hospital and when an intra-operative cholangiogram was not performed. Over the study period, the rate of repeat cholecystectomy increased from 0.02% to 0.6%. Incidentally, the rate of intra-operative cholangiogram during a primary cholecystectomy increased from 43% to 73%. CONCLUSIONS: Repeat cholecystectomy is an uncommon procedure. A second cholecystectomy is a more complex and likely to require intensive care unit support. Referral to a tertiary hepatobiliary unit is recommended.

A systematic review on the complications and management of hepatic adenomas: a call for a new approach.

Hepatic adenomas are benign hepatic lesions with heterogeneous characteristics. Awareness of complications, including haemorrhage and malignant transformation, has improved alongside a concurrent rise in their detection. Monitoring and management guidelines, however, remain inconsistent. This systematic review analyses the natural history of hepatic adenomas, and existing and novel risk factors associated with haemorrhage and malignant transformation. Results of this systematic review commonly identified male sex, and the beta-catenin histopathological hepatic adenoma subtype, as risk factors for malignant transformation, whilst those associated with haemorrhage included lesion size and number, exophytic nature, and recent hormone use. Overall, females demonstrated higher rates of haemorrhage, whilst males exhibited a higher risk of hepatocellular carcinoma development. This systematic review highlights that tumour size and subtype may not be as characteristically linked with complications as previously thought. We have additionally reported novel risk factors contributing to development of hepatic adenoma-related complications. We conclude by highlighting the risk of taking a conservative approach to seemingly low-risk lesions and suggest revised practice guidelines.

Characterization of distinct strains of an aphid-transmitted ilarvirus (Fam. Bromoviridae) infecting different hosts from South America.

Potato yellowing virus (PYV, original code SB-22), an unassigned member of the Genus Ilarvirus Family Bromoviridae, has been reported infecting potatoes in Peru, Ecuador and Chile. It is associated with symptomless infections, however yellowing of young leaves has been observed in some potato cultivars. Thirteen potato and yacon isolates were selected after routine screening of CIP-germplasm and twenty-four were identified from 994 potato plants collected in Peru whereas one was intercepted from yacon in the UK. These isolates were identified using high throughput sequencing, ELISA, host range and RT-PCR. Here we report the sequence characterization of the complete genomes of nine PYV isolates found infecting Solanum tuberosum, four complete genome isolates infecting Smallanthus sonchifolius (yacon), and in addition 15 complete RNA3 sequences from potato and partial sequences of RNA1, 2 and 3 of isolates infecting potato and yacon from Ecuador, Peru and Bolivia. Results of phylogenetic and recombination analysis showed RNA3 to be the most variable among the virus isolates and suggest potato infecting isolates have resulted through acquisition of a movement protein variant through recombination with an unknown but related ilarvirus, whereas one yacon isolate from Bolivia also had resulted from a recombination event with another related viruses in the same region. Yacon isolates could be distinguished from potato isolates by their inability to infect Physalis floridana, and potato isolates from Ecuador and Peru could be distinguished by their symptomatology in this host as well as phylogenetically. The non-recombinant yacon isolates were closely related to a recently described isolate from Solanum muricatum (pepino dulce), and all isolates were related to Fragaria chiloensis latent virus (FCiLV) reported in strawberry from Chile, and probably should be considered the same species. Although PYV is not serologically related to Alfalfa mosaic virus (AMV), they are both transmitted by aphids and share several other characteristics that support the previous suggestion to reclassify AMV as a member in the genus Ilarvirus.

Contrast-enhanced sonographic appearances of two primary hepatic epithelioid angiomyolipomas.

Epithelioid hepatic angiomyolipoma (Epi-HAML) is a rare hepatic tumor frequently misdiagnosed as hepatocellular carcinoma (HCC). Unlike conventional angiomyolipoma (AML), Epi-HAML contains minimal amount of adipose tissue, which is a radiological distinguishing feature between AML and HCC. Two patients were referred for management of incidentally found hepatic lesions confirmed to be Epi-HAML on post-resection tissue analysis. CT and MRI findings were suggestive of HCC. Contrast-enhanced ultrasound demonstrated intratumoral shunting, a feeding artery, and early draining hepatic vein. These findings should alert radiologists to the possibility of Epi-HAML. Furthermore, these features may be better assessed by contrast-enhanced ultrasound due to its superior dynamic temporal resolution.

Body Composition Adjusted Dosing of Gemcitabine-Nab-Paclitaxel in Pancreatic Cancer Does Not Predict Toxicity Compared to Body Surface Area Dosing.

Combination gemcitabine and nab-paclitaxel (Gem-Nab-P) is a common regimen used to treat metastatic pancreatic ductal adenocarcinoma (PDAC). Toxicity from this regimen is associated with significant morbidity. Currently, Gem-Nab-P is dosed using estimated body surface area, derived from height and weight. This study investigates whether skeletal muscle assessment could be a useful tool in the dosing of Gem-Nab-P in metastatic PDAC. This study included 52 patients who had received first-line treatment with Gem-Nab-P for PDAC. Demographic and chemotherapy treatment information was gathered from medical records and body composition analysis was performed using single slice computed tomography methods, at spinal level L3. Patients who experienced first-cycle chemotherapy-associated toxicity did not have a different median skeletal muscle area (SkMA) to those who did not (128.6 cm2 vs. 111.4 cm2, P = 0.2). There was also no difference in the gemcitabine dose to SkMA ratio (14.1 mg/cm2 vs. 14.4 mg/cm2, P = 0.8), nab-paclitaxel to SkMA ratio (1.8 mg/cm2 vs. 1.8 mg/cm2, P = 0.6) or combined dose equivalent to SkMA ratio (2.8 mg/cm2 vs. 2.9 mg/cm2, P = 0.9) between the patients that experienced first cycle toxicity versus those that did not. This study suggests that a PDAC patient's SkMA is unlikely to be a useful addition to conventional body surface area in the dosing of first-line Gem-Nab-P, to reduce first-cycle toxicity.

Neoadjuvant therapy and major arterial resection for potentially reconstructable arterial involvement by stage 3 adenocarcinoma of the pancreas.

BACKGROUND: Stage 3 pancreatic ductal adenocarcinoma (PDAC) is defined by arterial involvement. This study objective was to evaluate outcomes for patients with stage 3 PDAC with potentially reconstructable arterial involvement, considered for neoadjuvant therapy (NAT) and pancreatic resection, and to compare outcomes following arterial (AR) and non-arterial resection (NAR). METHODS: This study included patients from 2009 to 2016 with biopsy-proven stage 3 PDAC who were offered NAT before surgical exploration. AR was performed if required to achieve R0 resection. Time to event outcomes were analysed from diagnosis date. RESULTS: 87/89 patients (97.8%) received NAT (chemotherapy 41.6%, chemotherapy/radiotherapy 56.2%). 46/89 (51.7%) underwent exploration; 31 underwent resection (AR n = 20, NAR n = 11). AR patients had longer operative time (681 vs. 563 min, p = 0.006) and more blood loss (1600 vs. 575 mL, p = 0.0004), with no difference for blood transfusion, pancreatic fistula, length of stay, reoperation, or mortality. R0 rate was 30/31. Post-resection 90-day mortality was 3.2%. Median overall survival was statistically comparable between the AR and NAR groups (19.7 vs. 28.4 months, p = 0.41). CONCLUSIONS: AR had comparable clinical and oncologic outcomes to NAR. Following careful selection and non-progression after NAT, major AR may cautiously be considered if required to obtain a negative resection margin.

Safety, efficacy and compliance of extended thromboprophylaxis in hepatobiliary and upper gastrointestinal surgery.

BACKGROUND: Extended venothromboprophylaxis (eVTP) after abdominal surgery for hepatobiliary (HPB) and upper gastrointestinal (UGI) malignancies is recommended. Safety, efficacy and compliance within this group of surgical patients are not well described. The primary aim was to assess safety and compliance of post-operative administration of eVTP with low molecular weight heparin. Secondary aim was to assess barriers to treatment and monitor the rate of post-operative venous thromboembolism. METHODS: A prospective observational cohort study of patients undergoing abdominal surgery for HPB or UGI malignancies was undertaken from January 2014 to June 2016. All patients were assessed for eVTP. Demographics, clinical outcomes and clinical questionnaires on discharge and at follow-up 6 weeks post their initial surgery were used to assess the safety, compliance and efficacy of eVTP. RESULTS: A total of 100 patients were assessed for post-operative eVTP. Of these, 80 patients were prescribed 28 days of low molecular weight heparin. Of 80 patients, 65 (85%) patients completed the full eVTP, 11 (13%) missed 1-5 injections and only four (6%) missed 6-15 injections. In the 80 eVTP patients, there were no episodes of significant bleeding or venous thromboembolism. A total of nine (11%) patients would be unwilling to undertake eVTP again for a variety of reasons, including ease of disposal of syringes and needle phobias. CONCLUSION: The administration of eVTP in patients undergoing major HPB and UGI surgery is safe, with minimal morbidity and high compliance. The greatest barrier to administration is doctor prescription.

Hepatic cystic echinococcosis in Australia: an update on diagnosis and management.

BACKGROUND: Echinococcosis is an uncommonly encountered zoonotic disease caused by the taeniid Echinococcus. The only endemic species in Australia, Echinococcus granulosus, forms cysts in the liver in 70% of cases. The aim of this study was to review the literature to provide an evidence-based narrative update on the diagnosis and management of hepatic cystic echinococcosis in Australia. METHODS: We reviewed the literature, utilizing multiple research databases and citation tracking. Original research and review articles examining the diagnosis and management of hydatid disease in adults, published prior to 2016 and in the English language were included in our review. RESULTS: Ultrasound is the gold-standard screening test, whilst computed tomography has a role in emergency presentations and screening for multi-organ involvement. Magnetic resonance imaging is the preferred second-line imaging and better demonstrates biliary involvement. Medical therapy or PAIR (percutaneous aspiration, irrigation with scolicide and re-aspiration) may be appropriate in selected cases; however, surgery remains the definitive treatment for active, large (>5 cm), symptomatic or complicated cysts. A variety of surgical techniques have been described, including conservative, radical and minimally invasive procedures. There is currently no consensus approach; surgical modality should be tailored to patient factors, relevant anatomy, local facilities and surgeons' expertise. CONCLUSION: Diagnosis and therapy in hepatic hydatid cysts have been significantly advanced by imaging, interventional radiology and surgical approaches in recent years. Surgery remains the mainstay of treatment for large, active, complicated or symptomatic hepatic hydatid cysts.

Endoscopic sphincterotomy with sphincteroplasty for the management of choledocholithiasis: a single-centre experience.

BACKGROUND: Balloon dilatation of the ampulla at endoscopic retrograde cholangiopancreatography (ERCP) is increasingly utilized in the management of large bile duct stones. The aim of this study was to review and compare the outcomes of using endoscopic sphincterotomy with endoscopic balloon dilatation (sphincteroplasty) in a combined approach as a single-stage (immediate) or a two-stage procedure (delayed). METHODS: A retrospective review of medical records for all patients undergoing ERCP and balloon dilatation for choledocholithiasis between January 2010 and December 2012 was undertaken. Outcomes measured included patient demographics, stone size, degree of dilatation performed, success of stone extraction, number of procedures required for duct clearance and procedure-related complications. RESULTS: One hundred and thirty-six ERCPs were performed with balloon sphincteroplasty. One hundred and four had a previous sphincterotomy with a delayed balloon dilatation and 32 had sphincterotomy with immediate dilatation. The overall clearance rate of the common bile duct for immediate and delayed groups was 93% (28/30) and 93% (81/87), respectively. Bile duct clearance after the first procedure was achieved in 70% (21/30) of patients in the immediate group and 74% (64/87) in the delayed group. There were six complications in the delayed group and four in the immediate group. The most frequently used balloon size was 10 mm for both groups with mean sizes of 10.34 (2.93) and 11.73 (2.87) in the immediate and delayed groups, respectively. CONCLUSION: Our study suggests that use of a combined approach is safe and effective and may provide benefits over using endoscopic balloon dilatation or endoscopic sphincterotomy alone in the treatment of choledocholithiasis.