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First-line palliative chemotherapy regimens in advanced pancreatic ductal adenocarcinoma (PDAC) have not been compared in head-to-head phase III randomised controlled trials (RCT). Data on optimum first-line treatment and subsequent sequencing is lacking. To compare overall survival (OS) between first-line treatment regimens in a real-world population to determine if an optimal therapeutic sequence is associated with survival benefit. A retrospective analysis of prospectively collated data from the Australasian PURPLE pancreatic cancer registry was undertaken. From 2016 to 2020, of 1551 pancreatic cancer patients, 615 received palliative-intent chemotherapy. Patients with early-stage resected disease without recurrence (n = 369), radiotherapy alone (n = 43), received supportive care alone (n = 458) or had less than 3 months follow-up (n = 66) were excluded. Median OS was comparable between patients receiving first-line Gemcitabine/Nab-Paclitaxel (n = 376) and those receiving FOLFIRINOX (n = 73) (11.3 versus 12.3 months, P = 0.37), with 38% proceeding to second-line chemotherapy which was associated with longer mOS compared to first-line treatment alone (17.4 versus 8.2 months, P < 0.001). With second-line treatment following prior FOLFIRINOX (n = 29) or Gemcitabine/Nab-Paclitaxel (n = 101), mOS did not differ significantly (17.3 versus 15.9 months, P = 0.92), respectively, whilst median progression-free survival was longer with prior FOLFIRINOX (5.2 versus 2.9 months, P = 0.03). There was no significant difference in overall survival between either first-line chemotherapy choice, despite patients receiving FOLFIRINOX being younger, fitter, and more likely to have localised disease. However, FOLFIRINOX was associated with delayed progression. In the absence of phase III RCT data, clinicians should be comfortable using either Gemcitabine/Nab-Paclitaxel or FOLFIRINOX as first-line therapy in advanced PDAC. • Analysis of optimal therapeutic sequencing in advanced pancreatic cancer (n = 615). • 1st-line FFX efficacy comparable to GEM-P (mOS 11.3 versus 12.3 months P = 0.37). • Longer mOS with 2nd-line chemotherapy versus 1st-line only (17.4 versus 8.2 months P < 0.001). • 2nd-line 5FU versus GEM-based treatment mOS similar (17.3 versus 15.9 months P = 0.92). [ABSTRACT FROM AUTHOR]

Background: Laparoscopic surgery is regarded as the gold standard for the surgical management of cholelithiasis. To improve post-operative pain, low-pressure laparoscopic cholecystectomies (LPLC) have been trialed. A recent systematic review found that LPLC reduced pain; however, many of the randomised control trials were at a high risk of bias and the overall quality of evidence was low. Methods: One hundred patients undergoing elective laparoscopic cholecystectomy were randomised to a LPLC (8 mmHg) or a standard pressure laparoscopic cholecystectomy (12 mmHg) (SPLC) with surgeons and anaesthetists blinded to the pressure. Pressures were increased if vision was compromised. Primary outcomes were post-operative pain and analgesia requirements at 4–6 h and 24 h. Results: Intra-operative visibility was significantly reduced in LPLC (p<0.01) resulting in a higher number of operations requiring the pressure to be increased (29% vs 8%, p=0.010); however, there were no differences in length of operation or post-operative outcomes. Pain scores were comparable at all time points across all pressures; however, recovery room fentanyl requirement was more than four times higher when comparing 8 to 12 mmHg (12.5mcg vs 60mcg, p=0.047). Nausea and vomiting was also higher when comparing these pressures (0/36 vs 7/60, p=0.033). Interestingly, when surgeons estimated the operating pressure, they were correct in only 69% of cases. Conclusion: Although pain scores were similar, there was a significant reduction in fentanyl requirement and nausea/vomiting in LPLC. Although LPLC compromised intra-operative visibility requiring increased pressure in some cases, there was no difference in complications, suggesting LPLC is safe and beneficial to attempt in all patients. Trial Registration: Registered with the Australia and New Zealand Clinical Trials Registry (ACTRN12619000205134). [ABSTRACT FROM AUTHOR]

Undercarboxylated osteocalcin (ucOC) improves glucose metabolism; however, its effects on endothelial cell function are unclear. We examined the biological effect of ucOC on endothelial function in animal models ex vivo and human cells in vitro. Isometric tension and immunohistochemistry techniques were used on the aorta of male New Zealand white rabbits and cell culture techniques were used on human aortic endothelial cells (HAECs) to assess the effect of ucOC in normal and high‐glucose environments. Overall, ucOC, both 10 and 30 ng/ml, did not significantly alter acetylcholine‐induced blood vessel relaxation in rabbits (p >.05). UcOC treatment did not cause any significant changes in the immunoreactivity of cellular signalling markers (p >.05). In HAEC, ucOC did not change any of the assessed outcomes (p >.05). UcOC has no negative effects on endothelial function which is important to reduce the risks of off target adverse effects if it will be used as a therapeutic option for metabolic disease in the future. [ABSTRACT FROM AUTHOR]

Introduction: The purpose of this study is to describe the patterns of practice in Australia and New Zealand for post-operative radiotherapy in endometrial cancer with cervical stromal involvement.Methods: A ten-item survey including five clinical case scenarios in endometrial cancer with cervical stromal invasion was emailed to Royal Australian and New Zealand College of Radiologists (RANZCR) radiation oncologists in 2018. Responses were analysed to determine relative frequency distributions and preferred adjuvant treatment modalities for the clinical case scenarios.Results: A total of 65 respondents initiated the survey with 27 respondents treating more than 11 endometrial cancer cases annually. Only 31 respondents answered all five clinical case scenarios. Preferred adjuvant radiotherapy modalities varied for the Stage II cases between vault brachytherapy (VB), pelvic external beam radiotherapy (EBRT) or a combination. For the stage IIIA and IIIC1 cases, the majority recommended pelvic EBRT with or without VB boost (79% and 77%), and of these, most combined with chemotherapy (61% and 88%). For 4 of the 5 case scenarios, when pelvic EBRT was offered, most recommended a VB boost.Conclusion: This patterns of practice survey suggests variability in adjuvant radiotherapy recommendations in endometrial cancer with cervical involvement, particularly in cases where there is lack of randomised data and discrepancies in consensus guidelines. [ABSTRACT FROM AUTHOR]

Low circulating levels of undercarboxylated osteocalcin (ucOC) is associated with a higher risk of cardiovascular disease, yet whether ucOC has a direct effect on endothelium-dependent vasorelaxation, or in proximity to its postulated receptor, the class CG protein-coupled receptor (GPCR6A), in blood vessels remains unclear. Immunohistochemistry and proximity ligation assays were used to localize the presence of ucOC and GPRC6A and to determine the physical proximity (< 40 nm) in radial artery segments collected from patients undergoing coronary artery bypass surgery (n = 6) which exhibited calcification (determined by Von Kossa) and aorta from New Zealand white rabbits exhibiting atherosclerotic plaques. Endothelium-dependent vasorelaxation was assessed using cumulative doses of acetylcholine in vitro on abdominal aorta of rabbits fed a normal chow diet (n = 10) and a 4-week atherogenic diet (n = 9) pre-incubated with ucOC (10 ng/mL) or vehicle. Both ucOC and GPRC6A were localized in human and rabbit diseased-blood vessels. Proximity ligation assay staining demonstrated physical proximity of ucOC with GPRC6A only within plaques in rabbit arteries and the endothelium layer of rabbit arterioles. Endothelium-dependent vasorelaxation was impaired in atherogenic abdominal aorta compared to healthy aorta and ucOC attenuated this impairment. ucOC attenuated impaired endothelium-dependent vasorelaxation in rabbit abdominal aorta following an atherogenic diet, however, this effect may be independent of GPRC6A. It is important that future studies determine the underlying cellular mechanisms by which ucOC effects blood vessels as well as whether it can be used as a therapeutic agent against the progression of atherosclerosis. [ABSTRACT FROM AUTHOR]