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.

Association of metabolic-bariatric surgery with long-term survival in adults with and without diabetes: a one-stage meta-analysis of matched cohort and prospective controlled studies with 174 772 participants.

BACKGROUND: Metabolic-bariatric surgery delivers substantial weight loss and can induce remission or improvement of obesity-related risks and complications. However, more robust estimates of its effect on long-term mortality and life expectancy-especially stratified by pre-existing diabetes status-are needed to guide policy and facilitate patient counselling. We compared long-term survival outcomes of severely obese patients who received metabolic-bariatric surgery versus usual care. METHODS: We did a prespecified one-stage meta-analysis using patient-level survival data reconstructed from prospective controlled trials and high-quality matched cohort studies. We searched PubMed, Scopus, and MEDLINE (via Ovid) for randomised trials, prospective controlled studies, and matched cohort studies comparing all-cause mortality after metabolic-bariatric surgery versus non-surgical management of obesity published between inception and Feb 3, 2021. We also searched grey literature by reviewing bibliographies of included studies as well as review articles. Shared-frailty (ie, random-effects) and stratified Cox models were fitted to compare all-cause mortality of adults with obesity who underwent metabolic-bariatric surgery compared with matched controls who received usual care, taking into account clustering of participants at the study level. We also computed numbers needed to treat, and extrapolated life expectancy using Gompertz proportional-hazards modelling. The study protocol is prospectively registered on PROSPERO, number CRD42020218472. FINDINGS: Among 1470 articles identified, 16 matched cohort studies and one prospective controlled trial were included in the analysis. 7712 deaths occurred during 1·2 million patient-years. In the overall population consisting 174 772 participants, metabolic-bariatric surgery was associated with a reduction in hazard rate of death of 49·2% (95% CI 46·3-51·9, p<0·0001) and median life expectancy was 6·1 years (95% CI 5·2-6·9) longer than usual care. In subgroup analyses, both individuals with (hazard ratio 0·409, 95% CI 0·370-0·453, p<0·0001) or without (0·704, 0·588-0·843, p<0·0001) baseline diabetes who underwent metabolic-bariatric surgery had lower rates of all-cause mortality, but the treatment effect was considerably greater for those with diabetes (between-subgroup I2 95·7%, p<0·0001). Median life expectancy was 9·3 years (95% CI 7·1-11·8) longer for patients with diabetes in the surgery group than the non-surgical group, whereas the life expectancy gain was 5·1 years (2·0-9·3) for patients without diabetes. The numbers needed to treat to prevent one additional death over a 10-year time frame were 8·4 (95% CI 7·8-9·1) for adults with diabetes and 29·8 (21·2-56·8) for those without diabetes. Treatment effects did not appear to differ between gastric bypass, banding, and sleeve gastrectomy (I2 3·4%, p=0·36). By leveraging the results of this meta-analysis and other published data, we estimated that every 1·0% increase in metabolic-bariatric surgery utilisation rates among the global pool of metabolic-bariatric candidates with and without diabetes could yield 5·1 million and 6·6 million potential life-years, respectively. INTERPRETATION: Among adults with obesity, metabolic-bariatric surgery is associated with substantially lower all-cause mortality rates and longer life expectancy than usual obesity management. Survival benefits are much more pronounced for people with pre-existing diabetes than those without. FUNDING: None.

Metabolic outcomes after revisional bariatric surgery: a systematic review and meta-analysis.

BACKGROUND: It has been well-established that primary bariatric surgery is effective in inducing improvement of diabetes and other associated co-morbidities in patients with obesity. Evidence demonstrating the influence of revisional bariatric surgery on this trajectory, however, is lacking. OBJECTIVES: We performed a systematic review and meta-analysis to examine the impact of revisional bariatric surgery on obesity-related metabolic outcomes. SETTING: University Hospital, Singapore METHODS: We examined outcomes of remission and improvement of diabetes, hypertension, hyperlipidemia, and obstructive sleep apnea. Revisional surgeries included sleeve gastrectomy, Roux-en-Y gastric bypass, pouch revision, duodenal switch, and minigastric bypass. RESULTS: Our search identified 33 relevant studies including a total of 1593 patients. Meta-analysis of proportions demonstrated a 92% improvement in diabetes with 50% achieving remission after revisional bariatric surgery. Of patients, 81% achieved improvement of hypertension with 33% achieving complete remission. In both groups, the highest proportion of improvement was observed after revisional duodenal switch. Although reported by fewer studies, a remission of hyperlipidemia was reported in 37% of patients and improvement of obstructive sleep apnea was seen in 86% of patients. CONCLUSIONS: Revisional bariatric surgery improves the outcomes of obesity-related co-morbidities and should be considered in patients with persistent metabolic disease after primary bariatric surgery.

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.

Is Laparoscopic Sleeve Gastrectomy for Asian Super Obese a Safe and Effective Procedure?

INTRODUCTION: Outcomes of bariatric surgery for super obese Asians are not well reported. We aimed to compare short-term outcomes of laparoscopic sleeve gastrectomy (LSG) in Asian patients with body mass index (BMI) <47.5 kg/m2 to those with BMI •••••• ≥47.5 kg/m2. MATERIALS AND METHODS: A total of 272 patients from Singapore university hospital who underwent LSG from 2008 to 2015 with a follow-up of at least 6 months were included in the study. Primary endpoint was weight loss at 1-year and 3-years. Morbid obesity (Group 1, G1) was defined as BMI <47.5 kg/m2 and super obesity (Group2, G2) was defined as BMI ≥47.5 kg/m2. RESULTS: There were 215 patients in G1 and 57 patients in G2 (mean preoperative weight: 107.3 kg and 146.8 kg; mean follow-up: 27.9 and 26.8 months, respectively). Mean total weight loss at 3-year of 41.9 kg for G2 was significantly higher (P = 0.003) than 27.2 kg for G1. Mean percentage excess weight loss (EWL) did not differ at 3-years. There was no difference in operating time, blood loss, length of stay, 30-day morbidity and readmission. There were no conversions and mortality in both groups. Remission of herpertension (P - 0.001) and dyslipidaemia (P = 0.038) were significantly associated with achieving EWL percentage (%EWL) >50 in G1. CONCLUSION: LSG is an equally safe and effective operation in Asians with BMI ≥47.5 kg/m2 when compare to patients with BMI <47.5 kg/m2 in achieving significant weight loss and improvement in comorbidities. Super obese lose more weight but have lower %EWL.

Early weight loss after laparoscopic sleeve gastrectomy predicts midterm weight loss in morbidly obese Asians.

BACKGROUND: Laparoscopic sleeve gastrectomy (SG) is a popular bariatric procedure in morbidly obese Asians. OBJECTIVES: To investigate the effect of initial weight loss on midterm weight maintenance and remission of co-morbidities after laparoscopic SG in morbidly obese Asians. SETTING: University Hospital, Singapore. METHODS: Data of patients who underwent laparoscopic SG were analyzed. Change in body mass index (BMI), percentage of total weight loss (%WL), and of excess weight loss (%EWL) was calculated and remission of obesity-related co-morbidities was examined. Linear regression analysis was performed to determine the effect of initial weight loss on successful weight maintenance. Receiver operative characteristic curve analysis was used to define optimal cutoff values. RESULTS: Two hundred and seventy-two patients were included in this study. Mean preoperative weight and BMI were 115.4±25.5 kg and 42.5±8.0 kg/m2, respectively. Mean follow-up duration was 27.6±16.4 months. Successful weight loss of>50% EWL was achieved by 65.7%, 65.5%, and 50.8% of patients at 1, 2, and 3 years, postoperatively. There was a significant correlation of %EWL at 3 months with %EWL up to 3 years (P≤.005). Receiver operative characteristic analysis showed initial EWL of 35% at 3 months best predicted successful weight loss at 1 year (sensitivity 73.1%, specificity 81.4%). Patients achieving>35% EWL were significantly more likely to achieve remission of co-morbidities (P≤.005) at 1 year after surgery. CONCLUSION: Early weight loss at 3 months predicts weight maintenance up to 3 years and remission of co-morbidities at 1 year after laparoscopic SG in Asians.

The diagnosis and management of H. pylori infection in Singapore.

Helicobacter pylori (H. pylori) is an infection that has a role in causing dyspepsia and complications such as peptic ulcer disease and gastric malignancies. In the primary care setting, one can adopt a stepwise approach with the 'test-and-treat' strategy to manage H. pylori-associated dyspepsia in young patients without alarm symptoms. Empiric first-line therapies should be for a two-week duration; options include clarithromycin-containing triple therapy alone or with the addition of bismuth, concomitant therapy and bismuth quadruple therapy. Post-treatment carbon urea breath test must be performed at least four weeks after the end of treatment to confirm the cure. Options for empiric second-line treatment include bismuth quadruple therapy and levofloxacin-containing triple therapy. Patients with persistent or alarm symptoms should be referred for further evaluation. Patients with persistent infection should be referred for gastroscopy so that gastric biopsies can be obtained for H. pylori culture and antibiotic susceptibility testing.

Revisional Bariatric Surgery: Focus on Quality of Life.

Bariatric surgery is considered to be the most effective treatment for morbid obesity. At present, revisional surgery is considered in patients who experience complications, or in whom the intended weight loss is not achieved. However, as there is no consensus on what constitutes failure of primary surgery, there are no guidelines on who should receive revisional surgery. Physical parameters alone may be insufficient and quality of life has emerged as an alternative to provide a holistic appraisal of the outcome of primary surgery and the need for further revisional surgery in bariatric patients. Quality of life surveys such as short form health survey (SF-36) or Moorehead-Ardelt II (MA-II) assess the patients' perception of their weight and can also be used to assess the impact of post-operative complications such as gastro-esophageal reflux disease or dysphagia. However, unrealistic expectations of weight loss have been shown to be prevalent in bariatric patients and patients who seek revisional surgery on the basis of disappointment with the primary outcome are unlikely to be satisfied with the revisional outcome. Indications for re-operative surgery must be tailored to improve the quality and longevity of each individual patient's life. Long term studies are required to investigate and validate quality of life as an indication for revisional surgery.