Locally invasive recurrence or metastasis of pheochromocytoma into the liver?-clinicopathological challenges.

Pheochromocytomas (PCC) are rare and functional neuroendocrine tumors developing from adrenal chromaffin cells. Predicting malignant behavior especially in the absence of metastasis can be quite challenging even in the era of improved understanding of the molecular mechanisms involved in PCCs. Currently, two histopathological grading systems Pheochromocytoma of the Adrenal Gland Scaled Score (PASS) and Grading of Adrenal Pheochromocytoma and Paraganglioma (GAPP) score are used in clinical practice, but these are subject to significant interobserver variability. Some of the most useful clinical factors associated with malignancy are large size ([4-5 cm), and genetic features such as presence of SDHB germline mutations. Local invasion is uncommon in PCC and metastasis seen in 10 to 17% but higher in germline mutations and when this occurs management can be challenging. Here, we report on a case with challenges faced by the pathologist and clinicians alike in diagnosis and management of PCC recurrence.

Living donor hepatectomy in medium volume liver transplant centre has comparable outcomes to high volume centres: validation of donabedian quality assurance framework.

BACKGROUND: Given the complexity of living donor hepatectomy, it is expected that high hospital volume will better outcomes. This study aims to evaluate post-operative outcomes for living donor hepatectomy in a medium volume liver transplant centre and compare to outcomes in high volume centres. Also, it serves as a validation tool for framework of structure-process-outcome model for safe living donor hepatectomy program. METHODS: 204 donors who underwent donor hepatectomy between June 1996 to September 2019 were reviewed retrospectively and compared to outcomes in high volume centres. RESULTS: At 6 months, overall donor morbidity rate was 20/204 (9.8%). Wound complications were most common at 5/204 (2.5%). Majority of complications were either Clavien grade 1 or 2 and only 3 donors had Clavien grade 3 complications. There was zero donor mortality. DISCUSSION: Our centre's donor morbidity rate of 9.8% is the one of the lowest reported in the published literature. With increased experience, stringent donor selection and enhanced perioperative care by a multi-disciplinary team, outcomes in a medium volume centre can match the outcomes reported in high volume centres. The framework for quality in terms of structure, process and outcomes is presented which can be adopted for developing programs.

An international multicenter study of protocols for liver transplantation during a pandemic: A case for quadripartite equipoise.

BACKGROUND & AIMS: The outbreak of COVID-19 has vastly increased the operational burden on healthcare systems worldwide. For patients with end-stage liver failure, liver transplantation is the only option. However, the strain on intensive care facilities caused by the pandemic is a major concern. There is an urgent need for ethical frameworks to balance the need for liver transplantation against the availability of national resources. METHODS: We performed an international multicenter study of transplant centers to understand the evolution of policies for transplant prioritization in response to the pandemic in March 2020. To describe the ethical tension arising in this setting, we propose a novel ethical framework, the quadripartite equipoise (QE) score, that is applicable to liver transplantation in the context of limited national resources. RESULTS: Seventeen large- and medium-sized liver transplant centers from 12 countries across 4 continents participated. Ten centers opted to limit transplant activity in response to the pandemic, favoring a "sickest-first" approach. Conversely, some larger centers opted to continue routine transplant activity in order to balance waiting list mortality. To model these and other ethical tensions, we computed a QE score using 4 factors - recipient outcome, donor/graft safety, waiting list mortality and healthcare resources - for 7 countries. The fluctuation of the QE score over time accurately reflects the dynamic changes in the ethical tensions surrounding transplant activity in a pandemic. CONCLUSIONS: This four-dimensional model of quadripartite equipoise addresses the ethical tensions in the current pandemic. It serves as a universally applicable framework to guide regulation of transplant activity in response to the increasing burden on healthcare systems. LAY SUMMARY: There is an urgent need for ethical frameworks to balance the need for liver transplantation against the availability of national resources during the COVID-19 pandemic. We describe a four-dimensional model of quadripartite equipoise that models these ethical tensions and can guide the regulation of transplant activity in response to the increasing burden on healthcare systems.

Clinical management and outcomes of acute pancreatitis: Identifying areas for quality improvement in a tertiary Asian setting.

BACKGROUND: This study aims to review the clinical management of patients with acute pancreatitis in a tertiary institute in Singapore, and to identify areas qualiy improvement based on validation against the recommendations in the IAP/APA and the Japanese guidelines. METHODS: 391 patients from a prospective electronic database were included and reviewed for compliance to the International Association of Pancreatology (IAP)/American Pancreatic Association (APA) guidelines (2013) and the Japanase Guidelines (2015). RESULTS: The 90 day mortality was 8.4% for moderately severe and 11.9% for severe pancreatitis. The accuracy of SIRS in predicting severe acute pancreatitis on admission was 72.1% and at 48 h 80.8%. Only 61.1% patients had ultrasound scan during their admission of whom 32.9% had it within 24 h of admission. 18.3% patients with initial diagnosis of idiopathic pancreatitis had EUS. 50% received Ringer lactate for initial fluid resuscitation. 38.7% received antibiotics as prophylaxis. 21.4% with severe acute pancreatitis had early enteral nutrition. Only 21.4% patients with biliary pancreatitis had index admission cholecystectomy. CONCLUSION: The compliance to existing guidelines for management of acute pancreatitis is variable. Identifying gaps and implementing measures to address them allows for continued improvement in the management of patients with acute pancreatitis.

Does persistent anti-HBc positivity influence the prognosis of HBsAg-negative hepatocellular carcinoma? comparative outcomes of anti-Hbc positive versus anti-Hbc negative non-B non-C HCC.

BACKGROUND: To compare the presentations and outcomes of anti-HBc seropositive Hepatocellular Carcinoma (HBc-HCC) with anti-HBc seronegative (NHBc-HCC) patients in HBsAg negative Non-HBV Non-HCV (NBNC-HCC) HCC population. METHODS: 515 newly diagnosed HCC patients from January 2011 to September 2016 were retrospectively reviewed. 145 (66.5%) NHBc-HCC and 73 (33.5%) HBc-HCC patients were identified. Patient demographics, disease characteristics, details of treatments, recurrence and survival outcomes were analysed. RESULTS: A significantly lower proportion of HBc-HCC patients were diagnosed through surveillence (6.8% vs 26.2%, p = 0.001). HBc-HCC patients were less likely cirrhotic (p < 0.001), portal hypertensive (p < 0.001), ascitic (p = 0.008) and thrombocytopenic (p = 0.003). A higher proportion of HBc-HCC patients had treatment with curative intent (46.6% vs 30.3%, p = 0.018) and surgery (39.7% vs 16.6%, p < 0.001). Although HBc-HCC patients had larger median tumor size (74.0 mm vs 55.0 mm, p = 0.016) with a greater proportion of patients having tumors ≥5 cm, there was no difference in the overall median survival (19.0 months vs 22.0 months, p = 0.919) and recurrence rates (38.2% vs 40.9%). CONCLUSION: Isolated anti-HBc seropositivity in HbsAg negative patients tend to present incidentally with delayed diagnoses resulting in larger tumors, but their long-term survival remain comparable.

A predictive nomogram to identify factors influencing the success of a concomitant laparoscopic cholecystectomy with common bile duct exploration for choledocholithiasis.

BACKGROUND: Single-staged laparoscopic common bile duct exploration (LCBDE) offers clear benefits in terms of cost and shorter hospitalization stays. However, a failed LCBDE requiring conversion to open surgery is associated with increased morbidity. This study reviewed the factors determining success of LCBDE, and created a predictive nomogram to stratify patients for the procedure. METHODS: A retrospective analysis of 109 patients who underwent LCBDE was performed. A nomogram was developed from factors significantly associated with conversion to open surgery and validated. RESULTS: Sixty-two patients underwent a successful LCBDE, while 47 patients required a conversion to open CBDE. The presence of underlying cholangitis (crude OR 2.70, 95% CI: 1.12-6.56, p = 0.017), together with its subsequent interventions, seemed to adversely increase the rate of conversion to open surgery. The predictive factors included in the nomogram for a failed laparoscopic CBDE included prior antibiotic use (adjusted OR (AOR) 2.98, 95% CI: 1.17-7.57, p = 0.022), previous ERCP (AOR 4.99, 95% CI: 2.02-12.36, p = 0.001) and abnormal biliary anatomy (AOR 9.37, 95% CI: 2.18-40.20, p = 0.003). CONCLUSION: LCBDE is useful for the treatment of choledocholithiasis. However, patients who were predicted to have an elevated risk for open conversion might not be ideal candidates for the procedure.

Outcomes of Percutaneous Cholecystostomy for Acute Cholecystitis.

BACKGROUND: Acute cholecystitis (AC) is an important cause of emergency admissions among the elderly. The use of percutaneous cholecystostomy (PC) as bridging therapy among high-risk patients is widely accepted. However, the use of PC as definitive treatment is controversial. AIM: To determine the characteristics, clinical outcomes and predictors of recurrence of AC among patients who underwent PC. METHODS: A retrospective case series of 71 consecutive patients [73 (38-96) years, 43/71 males] treated with PC for AC at a tertiary hospital from 2007 to 2013, with data collected from case records. RESULTS: Patients were followed up for 37.0 (0.1-110.8) months after PC. Mortality rate was 8.5 % (6/71) during the index admission and 32.4 % (23/71) at the end of follow-up. Recurrence rate for AC was 11.9 % (7/59). Median time to recurrence was 62 (13-464) days. PC was definitive treatment in 33/59. Predictors of recurrence were higher serum alkaline phosphatase (ALP) at diagnosis (OR = 1.01, 95 % CI 1.00-1.02, p = 0.021) and acute myocardial infarction (AMI) during index admission (OR = 8.00, 95 % CI 1.19-54.0, p = 0.033). Fifteen patients (26.3 %, 15/71) had post-procedural complications including dislodgement (14 %, 10/71), tube obstruction (7.0 %, 5/71), bile leaks (2.8 %, 2/71), gallbladder perforation (1.4 %, 1/71), bowels perforation (1.4 %, 1/71) and severe post-procedural haemorrhage (1.4 %, 1/71). CONCLUSION: PC is effective and relatively safe in high-risk patients with AC. However, patients with higher ALP or AMI during index admission have higher risk of recurrence and might benefit from definitive cholecystectomy.

A randomized controlled trial comparing post-operative pain in single-incision laparoscopic cholecystectomy versus conventional laparoscopic cholecystectomy.

INTRODUCTION: An increasing body of evidence is being published about single-incision laparoscopic cholecystectomy (SILC), but there are no well-powered trials with an adequate evaluation of post-operative pain. This randomized trial compares SILC against four-port laparoscopic cholecystectomy (LC) with post-operative pain as the primary endpoint. METHODS: Hundred patients were randomized to either SILC (n = 50) or LC (n = 50). Exclusion criteria were (1) Acute cholecystitis; (2) ASA 3 or above; (3) Bleeding disorders; and (4) Previous open upper abdominal surgery. Patients and post-operative assessors were blinded to the procedure performed. The site and severity of pain were compared at 4 h, 24 h, 14 days and 6 months post-procedure using the visual analog scale; non-inferiority was assumed when the lower boundary of the 95% confidence interval of the difference was above -1 and superiority when p ≤ 0.05. RESULTS: The study arms were demographically similar. At 24 h post-procedure, SILC was associated with less pain at extra-umbilical sites (rest: p = 0.004; movement: p = 0.008). Pain data were inconclusive at 24 h at the umbilical site on movement; SILC was otherwise non-inferior for pain at all other points. Operating duration was longer in SILC (79.46 vs 58.88 min, p = 0.003). 8% of patients in each arm suffered complications (p = 1.000). Re-intervention rates, analgesic use, return to function, and patient satisfaction did not differ significantly. CONCLUSIONS: SILC has improved short-term pain outcomes compared to LC and is not inferior in both short-term and long-term pain outcomes. The operating time is longer, but remains feasible in routine surgical practice.

Metabolic syndrome after a liver transplantation in an Asian population.

BACKGROUND: With improvements in patient survival after a liver transplantation (LT), long-term sequelae such as metabolic syndrome (MS) have become increasingly common. This study aims to characterize the prevalence, associations and long-term outcomes of post-LTMS and its components in an Asian population. METHODS: A retrospective review of all adult patients who underwent LT at the National University Health System Singapore between December 1996 and May 2012 was performed. MS was defined using the Adult Treatment Panel (ATP) III criteria modified for an Asian population. RESULTS: The median age of this cohort of 90 patients was 50.0 (16.0-67.0) years, with a median follow-up duration of 60.0 (7.0-192.0) months. The prevalence of post-LTMS was 35.6%, diabetes mellitus (DM) 51.1%, hypertension 60.0%, obesity 26.7% and dyslipidaemia 46.7%. On univariate analysis, factors significantly associated with post-LT MS include female gender (P = 0.066), pre-LT respiratory comorbidities (P = 0.038), pre-LT obesity (P = 0.014), pre-LTDM (P < 0.001), pre-LT hypertension (P = 0.039), pre-LTMS (P < 0.001), prednisolone use ≥24 months (P = 0.005) and mycophenolate mofetil use ≥24 months (P = 0.035). On multivariate analysis, independent associations of post-LT MS were pre-LTDM (P = 0.011) and pre-LTMS (P = 0.024). There was no difference in long-term survival of patients with and without post-LTMS (P = 0.425). CONCLUSION: In conclusion, pre-LT components of the MS and the use of certain immunosuppressants are related to developing post-LTMS.

Retained stone retrieval basket causing chronic pancreatitis: a case report.

Background: Endoscopic retrograde cholangiopancreatography is a common procedure performed for choledocholithiasis and gallstone pancreatitis. Although a relatively low risk procedure, it is not without its complications. Cases of impacted Dormia baskets during stone retrieval have been reported, but these are usually retrieved surgically during the same setting. Case summary: A 40-year-old man presented to our hospital with an episode of epigastric pain and discomfort. He has a prior background of recurrent episodes of pancreatitis of which he underwent prior endoscopic therapy in his home country. Initial investigations revealed a metallic object seen on abdominal x-ray, computer tomographic scan of the abdomen and pelvis, and magnetic resonance imaging of the pancreas. Further evaluation was done with endoscopy, which revealed a retained stone extraction basket from a previous endoscopic retrograde pancreatography, resulting in recurrent episodes of acute chronic pancreatitis. Although the retained foreign body was removed, he subsequently developed further complications of portal vein thrombosis as a result of recurrent acute chronic pancreatitis, which required anticoagulation. Conclusion: This case highlights the importance of retrieving any foreign body from the pancreas, especially on the head, to prevent the development of further complications.

Safely Implementing a Program of Pure Laparoscopic Donor Right Hepatectomy: The Experience From a Southeast Asian Center.

Laparoscopic donor right hepatectomy (LDRH) is a technically challenging procedure. There is increasing evidence demonstrating the safety of LDRH in high-volume expert centers. We report our center's experience in implementing an LDRH program in a small- to medium-sized transplantation program. Methods: Our center systematically introduced a laparoscopic hepatectomy program in 2006. We started with minor wedge resections followed by major hepatectomies with increasing complexities. In 2017, we performed our first laparoscopic living donor left lateral sectionectomy. Since 2018, we have performed 8 cases of right lobe living donor hepatectomy (laparoscopy-assisted: 4 and pure laparoscopic: 4). Results: The median operative time was 418 (298-540) min, whereas the median blood loss was 300 (150-900) mL. Two patients (25%) had surgical drain placed intraoperatively. The median length of stay was 5 (3-8) d, and the median time to return to work was 55 (24-90) d. None of the donors sustained any long-term morbidity or mortality. Conclusions: Small- to medium-sized transplant programs face unique challenges in adopting LDRH. Progressive introduction of complex laparoscopic surgery, a mature living donor liver transplantation program, appropriate patient selection, and the invitation of an expert to proctor the LDRH are necessary to ensure success.

Impact of donor age on recipient morbidity and mortality after living donor liver transplantation.

BACKGROUND: Evidence for use of graft from older donors in living donor liver transplantation (LDLT) has been conflicting. This study aims to clarify the impact of donor age on recipient morbidity and mortality after adult LDLT. METHODS: A total of 90 live liver donors and recipients who underwent primary adult-to-adult LDLT were divided into three groups according to donor age: donors in 20s (D-20s) group, donors in 30s and 40s (D-30s and 40s) group and donors in 50s & 60s (D-50s and 60s) group. Multivariate analyses were conducted to look for independent risk/prognostic factors. Donor age was analysed as a continuous variable to determine an optimal cut off. RESULTS: Overall donor morbidity was 4/90 (4.44%), major donor morbidity was 1/90 (1.11%) and there was no donor mortality. Recipients in the D-20s group had better 1-, 3- and 5-year recipient survival than recipients in the D-50s and 60s group (96%, 91%, 91% versus 73%, 58%, 58%, respectively) (P = 0.020). Donor age was identified to be an independently significant risk factor for increased major complications (P = 0.007) and prognostic factor for reduced overall survival (P = 0.014). The optimal donor age cut off was determined to be 46.5 years old. CONCLUSION: Older donors are associated with poorer recipient outcomes after adult-to-adult LDLT. Usage of liver grafts from older donors should be carefully considered when choosing liver grafts for patients undergoing LDLT.

Pan-cancer pervasive upregulation of 3' UTR splicing drives tumourigenesis.

Most mammalian genes generate messenger RNAs with variable untranslated regions (UTRs) that are important post-transcriptional regulators. In cancer, shortening at 3' UTR ends via alternative polyadenylation can activate oncogenes. However, internal 3' UTR splicing remains poorly understood as splicing studies have traditionally focused on protein-coding alterations. Here we systematically map the pan-cancer landscape of 3' UTR splicing and present this in SpUR ( http://www.cbrc.kaust.edu.sa/spur/home/ ). 3' UTR splicing is widespread, upregulated in cancers, correlated with poor prognosis and more prevalent in oncogenes. We show that antisense oligonucleotide-mediated inhibition of 3' UTR splicing efficiently reduces oncogene expression and impedes tumour progression. Notably, CTNNB1 3' UTR splicing is the most consistently dysregulated event across cancers. We validate its upregulation in hepatocellular carcinoma and colon adenocarcinoma, and show that the spliced 3' UTR variant is the predominant contributor to its oncogenic functions. Overall, our study highlights the importance of 3' UTR splicing in cancer and may launch new avenues for RNA-based anti-cancer therapeutics.

Evaluation of Adult Living Donor Liver Transplantation in Largest Southeast Asian Transplantation Center: Benchmarking With Adult-to-Adult Living Donor Liver Transplantation (A2ALL) Experience.

BACKGROUND: The volume-outcome relation for complex surgical procedures such as living donor liver transplantation (LDLT) generally favors high volume (HV) centers. It is important for low to medium volume (MV) centers to evaluate their centers' performance against HV centers to allow early detection and correction of potential systemic issues. There is a dearth of national and international comprehensive registries for LDLT that may allow reasonable risk-adjusted comparisons for benchmarking. This study aims to evaluate the LDLT program by comparing our center's performance against HV centers of the Adult-to-Adult Living Donor Liver Transplantation cohort. STUDY DESIGN: Patient outcomes from a MV transplant center were compared with 11 HV transplant centers from the Adult-to-Adult Living Donor Liver Transplantation cohort. Outcomes evaluated included length of hospital stay, same admission mortality, 90-day mortality, and overall survival. RESULTS: A total of 1381 patients were analzyed. HV 1 to 4, 6, 8, 9, and 11 centers had a shorter median length of hospital stay compared with the MV center (All Dunnett corrected P values all less than .05). HV 9 and 11 centers had lower same admission mortality compared with the MV center (Dunnett corrected P = .023 and .015). After adjusting for other significant predictors, the MV center had comparable 90-day mortality rates and overall survival rates to all HV centers. CONCLUSION: This benchmarking exercise has demonstrated that the limitation of low institutional case volume can be overcome with a protocol-based framework to implement a safe LDLT program. This framework presented can be adopted for developing programs.

Teaching Medical Research to Medical Students: a Systematic Review.

PHENOMENON: Research literacy remains important for equipping clinicians with the analytical skills to tackle an ever-evolving medical landscape and maintain an evidence-based approach when treating patients. While the role of research in medical education has been justified and established, the nuances involving modes of instruction and relevant outcomes for students have yet to be analyzed. Institutions acknowledge an increasing need to dedicate time and resources towards educating medical undergraduates on research but have individually implemented different pedagogies over differing lengths of time. APPROACH: While individual studies have evaluated the efficacy of these curricula, the evaluations of educational methods and curriculum design have not been reviewed systematically. This study thereby aims to perform a systematic review of studies incorporating research into the undergraduate medical curriculum, to provide insights on various pedagogies utilized to educate medical students on research. FINDINGS: Studies predominantly described two major components of research curricula-(1) imparting basic research skills and the (2) longitudinal application of research skills. Studies were assessed according to the 4-level Kirkpatrick model for evaluation. Programs that spanned minimally an academic year had the greatest proportion of level 3 outcomes (50%). One study observed a level 4 outcome by assessing the post-intervention effects on participants. Studies primarily highlighted a shortage of time (53%), resulting in inadequate coverage of content. INSIGHTS: This study highlighted the value in long-term programs that support students in acquiring research skills, by providing appropriate mentors, resources, and guidance to facilitate their learning. The Dreyfus model of skill acquisition underscored the importance of tailoring educational interventions to allow students with varying experience to develop their skills. There is still room for further investigation of multiple factors such as duration of intervention, student voluntariness, and participants' prior research experience. Nevertheless, it stands that mentoring is a crucial aspect of curricula that has allowed studies to achieve level 3 Kirkpatrick outcomes and engender enduring changes in students. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40670-020-01183-w.

The unspoken reality of gender bias in surgery: A qualitative systematic review.

OBJECTIVE: This study was conducted to better understand the pervasive gender barriers obstructing the progression of women in surgery by synthesising the perspectives of both female surgical trainees and surgeons. METHODS: Five electronic databases, including Medline, Embase, PsycINFO, CINAHL and Web of Science Core Collection, were searched for relevant articles. Following a full-text review by three authors, qualitative data was synthesized thematically according to the Thomas and Harden methodology and quality assessment was conducted by two authors reaching a consensus. RESULTS: Fourteen articles were included, with unfavorable work environments, male-dominated culture and societal pressures being major themes. Females in surgery lacked support, faced harassment, and had unequal opportunities, which were often exacerbated by sex-blindness by their male counterparts. Mothers were especially affected, struggling to achieve a work-life balance while facing strong criticism. However, with increasing recognition of the unique professional traits of female surgeons, there is progress towards gender quality which requires continued and sustained efforts. CONCLUSION: This systematic review sheds light on the numerous gender barriers that continue to stand in the way of female surgeons despite progress towards gender equality over the years. As the global agenda towards equality progresses, this review serves as a call-to-action to increase collective effort towards gender inclusivity which will significantly improve future health outcomes.

Multimodal prehabilitation before major abdominal surgery: A retrospective study.

INTRODUCTION: Prehabilitation may benefit older patients undergoing major surgeries. Currently, its efficacy has not been conclusively proven. This is a retrospective review of a multimodal prehabilitation programme. METHODS: Patients aged 65 years and above undergoing major abdominal surgery between May 2015 and December 2019 in the National University Hospital were included in our institutional programme that incorporated aspects of multimodal prehabilitation and Enhanced Recovery After Surgery concepts as 1 holistic perioperative pathway to deal with issues specific to older patients. Physical therapy, nutritional advice and psychosocial support were provided as part of prehabilitation. RESULTS: There were 335 patients in the prehabilitation cohort and 256 patients whose records were reviewed as control. No difference in postoperative length of stay (P=0.150) or major complications (P=0.690) were noted. Patients in the prehabilitation group were observed to ambulate a longer distance and participate more actively with their physiotherapists from postoperative day 1 until 4. In the subgroup of patients with cancer, more patients had undergone neoadjuvant therapy in the prehabilitation group compared to the control group (21.7% versus 12.6%, P=0.009). Prehabilitation patients were more likely to proceed to adjuvant chemotherapy (prehabilitation 87.2% vs control 65.6%, P<0.001) if it had been recommended. CONCLUSION: The current study found no differences in traditional surgical outcome measures with and without prehabilitation. An increase in patient mobility in the immediate postoperative period was noted with prehabilitation, as well as an association between prehabilitation and increased adherence to postoperative adjuvant therapy. Larger prospective studies will be needed to validate the findings of this retrospective review.

Impact of COVID-19 on Liver Transplantation in Hong Kong and Singapore: A Modelling Study.

BACKGROUND: Liver transplantation (LT) activities during the COVID-19 pandemic have been curtailed in many countries. The impact of various policies restricting LT on outcomes of potential LT candidates is unclear. METHODS: We studied all patients on the nationwide LT waitlists in Hong Kong and Singapore between January 2016 and May 2020. We used continuous time Markov chains to model the effects of different scenarios and varying durations of disruption on LT candidates. FINDINGS: With complete cessation of LT, the projected 1-year overall survival (OS) decreased by 3•6%, 10•51% and 19•21% for a 1-, 3- and 6-month disruption respectively versus no limitation to LT, while 2-year OS decreased by 4•1%, 12•55%, and 23•43% respectively. When only urgent (acute-on-chronic liver failure [ACLF] or acute liver failure) LT was allowed, the projected 1-year OS decreased by a similar proportion: 3•1%, 8•41% and 15•20% respectively. When deceased donor LT (DDLT) and urgent living donor LT (LDLT) were allowed, 1-year projected OS decreased by 1•2%, 5•1% and 8•85% for a 1-, 3- and 6-month disruption respectively. OS was similar when only DDLT was allowed. Complete cessation of LT activities for 3-months resulted in an increased projected incidence of ACLF and hepatocellular carcinoma (HCC) dropout at 1-year by 49•1% and 107•96% respectively. When only urgent LT was allowed, HCC dropout and ACLF incidence were comparable to the rates seen in the scenario of complete LT cessation. INTERPRETATION: A short and wide-ranging disruption to LT results in better outcomes compared with a longer duration of partial restrictions. FUNDING: None to disclose.

Liver transplantation for non-resectable colorectal liver metastases: the International Hepato-Pancreato-Biliary Association consensus guidelines.

Colorectal cancer is a prevalent disease worldwide, with more than 50% of patients developing metastases to the liver. Despite advances in improving resectability, most patients present with non-resectable colorectal liver metastases requiring palliative systemic therapy and locoregional disease control strategies. There is a growing interest in the use of liver transplantation to treat non-resectable colorectal liver metastases in well selected patients, leading to a surge in the number of studies and prospective trials worldwide, thereby fuelling the emerging field of transplant oncology. The interdisciplinary nature of this field requires domain-specific evidence and expertise to be drawn from multiple clinical specialities and the basic sciences. Importantly, the wider societal implication of liver transplantation for non-resectable colorectal liver metastases, such as the effect on the allocation of resources and national transplant waitlists, should be considered. To address the urgent need for a consensus approach, the International Hepato-Pancreato-Biliary Association commissioned the Liver Transplantation for Colorectal liver Metastases 2021 working group, consisting of international leaders in the areas of hepatobiliary surgery, colorectal oncology, liver transplantation, hepatology, and bioethics. The aim of this study was to standardise nomenclature and define management principles in five key domains: patient selection, evaluation of biological behaviour, graft selection, recipient considerations, and outcomes. An extensive literature review was done within the five domains identified. Between November, 2020, and January, 2021, a three-step modified Delphi consensus process was undertaken by the workgroup, who were further subgrouped into the Scientific Committee, Expert Panel, and Transplant Centre Representatives. A final consensus of 44 statements, standardised nomenclature, and a practical management algorithm is presented. Specific criteria for clinico-patho-radiological assessments with molecular profiling is crucial in this setting. After this, the careful evaluation of biological behaviour with bridging therapy to transplantation with an appropriate assessment of the response is required. The sequencing of treatment in synchronous metastatic disease requires special consideration and is highlighted here. Some ethical dilemmas within organ allocation for malignant indications are discussed and the role for extended criteria grafts, living donor transplantation, and machine perfusion technologies for non-resectable colorectal liver metastases are reviewed. Appropriate immunosuppressive regimens and strategies for the follow-up and treatment of recurrent disease are proposed. This consensus guideline provides a framework by which liver transplantation for non-resectable colorectal liver metastases might be safely instituted and is a meaningful step towards future evidenced-based practice for better patient selection and organ allocation to improve the survival for patients with this disease.