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Due to advances in modern medicine, liver transplantation has revolutionised the prognosis of many previously incurable liver diseases. This progress has largely been due to advances in immunosuppressant therapy. However, despite the judicious use of immunosuppression, many liver transplant recipients still experience complications such as rejection, which necessitates diagnosis via invasive liver biopsy. There is a clear need for novel, minimally-invasive tests to optimise immunosuppression and improve patient outcomes. An emerging biomarker in this ‘‘precision medicine’‘ liver transplantation field is that of donor-specific cell free DNA. In this review, we detail the background and methods of detecting this biomarker, examine its utility in liver transplantation and discuss future research directions that may be most impactful.

BACKGROUND: In Australia, ethics committees across different states vary in application, requirement and process for the ethical review and approval for clinical research. This may lead to confusion and delays in the enablement of multicentre research projects. This study explores the effect of differing processes for Ethics and Governance in the establishment of the CovidSurg-Cancer study during the global COVID-19 pandemic. METHODS: An anonymous, structured web-based questionnaire was designed using the Research Electronic Data Capture application (REDCap) platform to capture consultant surgeons, fellows, and trainees experience in the ethics application process. 'CovidSurg-Cancer' was an international multicentre collaborative study to assess the impact of COVID-19 on the outcomes of patients undergoing cancer surgery. The ethics process to set up this observational study was used as to explore the differing processes applied across Australia. RESULTS: The CovidSurg-Cancer study was successfully set up in 14 hospitals. Four hospitals approved the study directly as an audit. Of the remaining sites, 10 ethics applications underwent Human Research Ethics Committee review following which two (14%) were subsequently approved as an audit activity and eight hospitals (57%) were given formal ethical approval with waiver of consent. Ethics application acceptance from another Australian Human Research Ethics Committee was provided with six applications; however, only three were reciprocated without the requirement for further agreements. A third of (30%) respondents suggested that the details of the application pathway, process and documentation were unclear. CONCLUSION: Ethics processes are varied across Australia with considerable repetition. A centralized, harmonized application process would enhance collaborative research.

Background Despite improvements in the genetic and epigenetic analysis of cell-free DNA (cfDNA), there has been limited focus on assessing the preanalytical variables of recovery efficiency following cfDNA extraction and bisulfite modification. Quantification of recovery efficiency after these steps can facilitate quality assurance and improve reliability when comparing serial samples. Methods We developed an exogenous DNA Construct to Evaluate the Recovery Efficiency of cfDNA extraction and BISulfite modification (CEREBIS) after cfDNA extraction and/or subsequent bisulfite modification from plasma. The strategic placement of cytosine bases in the 180 bp CEREBIS enabled PCR amplification of the construct by a single primer set both after plasma DNA extraction and following subsequent bisulfite modification. Results Plasma samples derived from 8 organ transplant donors and 6 serial plasma samples derived from a liver transplant recipient were spiked with a known number of copies of CEREBIS. Recovery of CEREBIS after cfDNA extraction and bisulfite modification was quantified with high analytical accuracy by droplet digital PCR. The use of CEREBIS and quantification of its recovery was useful in identifying problematic extractions. Furthermore, its use was shown to be invaluable towards improving the reliability of the analysis of serial samples. Conclusions CEREBIS can be used as a spike-in control to address the preanalytical variable of recovery efficiency both after cfDNA extraction from plasma and following bisulfite modification. Our approach can be readily implemented and its application may have significant benefits, especially in settings where longitudinal quantification of cfDNA for disease monitoring is necessary.

BACKGROUND: Acute biliary pain is the most common presentation of gallstone disease. Untreated patients risk recurrent pain, cholecystitis, obstructive jaundice, pancreatitis and multiple hospital presentations. We examine the outcome of implementing a policy to offer laparoscopic cholecystectomy on index presentation to patients with biliary colic in a tertiary hospital in Australia. METHODS: This is a retrospective cohort study of adult patients presenting to the emergency department (ED) with biliary pain during three 12-month periods. Outcomes in Group A, 3 years prior to policy implementation, were compared with groups 2 and 7 years post implementation (Groups B and C). Primary outcomes were representations to ED, admission rate and time to cholecystectomy. RESULTS: A total of 584 patients presented with biliary colic during the three study periods. Of these, 391 underwent cholecystectomy with three Strasberg Type A bile leaks and no bile duct injuries. The policy increased admission rates (A = 15.8%, B = 62.9%, C = 29.5%, P < 0.001) and surgery on index presentation (A = 12.0%, B = 60.7%, C = 27.4%, P < 0.001). There was a decline in time to cholecystectomy (days) (A = 143, B = 15, C = 31, P < 0.001), post-operative length of stay (days) (A = 3.6, B = 3.2, C = 2.0, P < 0.05) and representation rates to ED (A = 42.1%, B = 7.1%, C = 19.9%, P < 0.001). There was a decline in policy adherence in the later cohort. CONCLUSION: Index hospital admission and cholecystectomy for biliary colic decrease patient representations, time to surgery, post-operative stay and complications of gallstone disease. This study demonstrates the impact of the policy with initial improvement, the dangers of policy attrition and the need for continued reinforcement.

Introduction Cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS) is a rare multisystem neurodegenerative disorder. We describe our perioperative evaluation and care of a patient with CANVAS undergoing a pancreaticoduodenectomy for an ampullary adenocarcinoma, with a focus on perioperative risk stratification and optimisation, intraoperative advanced haemodynamic monitoring and the postoperative care. Case presentation A 69-year-old female with CANVAS presented with asymptomatic obstructive jaundice, icterus and abdominal pain. She had limited mobility and deconditioning due to severe generalised neuropathy. Computed tomography confirmed a resectable periampullary tumour. Her Duke Activity Status Index was 8.25 points and Edmonton Frailty Scale score was 11, confirming moderate frailty. However, the Charlson Comorbidity Index was five, indicative of a 21% estimated 10-year survival. Further risk stratification including respiratory function testing, echocardiography and cardiopulmonary exercise testing was conducted. The patient proceeded with surgery after multidisciplinary discussions with her treating medical teams. Discussion CANVAS is a rare and challenging condition requiring careful perioperative planning and management. There is no effective treatment for CANVAS. The management approach focuses on mitigating symptoms and improving quality of life. Given that no specific guidelines for managing these patients in the perioperative period have been provided, this report highlights several critical medical issues and implications that should be considered for the successful management of these patients. We demonstrate the role of specific anaesthesia techniques and advanced haemodynamic monitoring in both preventing postoperative morbidity and optimising patient recovery. Conclusion CANVAS is a rare and challenging condition in anaesthesia requiring careful perioperative planning and management., Highlights • CANVAS is a rare multisystem neurological disorder • There is no effective treatment for CANVAS • Perioperative management for patients with CANVAS is complex • Perioperative risk stratification requires multidisciplinary involvement • CANVAS patients can present with unique anaesthesia challenges

The intraoperative delivery of medications for patients with Parkinson’s disease (PD) during prolonged surgery is challenging. In complex surgical procedures, PD medications are commonly delivered via a nasogastric tube. However, this technique is not feasible in procedures where the stomach is

We present the case of a 29-year-old woman who attended a surgical outpatient clinic with symptoms of perianal fissure due to syphilitic infection. This uncommon aetiology of a common condition is often alluded to in textbooks, but little information exists in the scientific literature regarding the pathogenesis, presentation and treatment of fissure-in-ano secondary to syphilis. We present the case and an overview of the topic aimed at surgeons and clinicians who manage patients with perianal pathology. Syphilis is far from a disease of antiquity; in patients presenting with fissure-in-ano a thorough sexual history and sexually transmissible infection screening in at-risk groups may avoid mis-diagnosis, community transmission and unnecessary procedures.

Background Endovascular intervention for chronic total occlusions (CTOs) in aortoiliac occlusive disease (AIOD) poses technical challenges. In this manuscript, our experience of fine needle recanalization for the treatment of iliac artery CTO is described. Method A prospective database recorded treatment of 11 limbs in 11 patients since 2011 using this technique. The majority of these CTO were of the common iliac artery (n = 9). Results Technical success rate was 91% (n = 10). One failed case was due to tortuous iliac anatomy. There was no restenosis of the treated segments at 8 weeks and no major complications, perforations, major limb loss, or periprocedural mortality. Conclusions This technique is a safe and viable adjunct for difficult CTO in AIOD with suitable anatomy. It benefits from being a simple, low-profile, low-cost coaxial system and should be part of the armamentarium with other advanced endovascular techniques.