Thoracic Epidural Analgesia for Postoperative Pain Management in Liver Transplantation: A 10-year Study on 685 Liver Transplant Recipients

Background. Thoracic epidural analgesia (TEA) is not widely used for postoperative pain management in liver transplantation due to hepatic coagulopathy-related increased risk of inducing an epidural hematoma. However, an increasing number of patients are transplanted for other indications than the end-stage liver disease and without coagulopathy allowing insertion of an epidural catheter. Methods. This study is a retrospective observational single-center study of all adult patients undergoing first-time liver transplantation at Oslo University Hospital between January 1, 2008, and December 31, 2017. Data regarding patient characteristics were obtained from the Nordic liver transplant registry, medical records, and pain registration forms. Patients without coagulopathy (international normalized ratio 100 × 109/L) were eligible for TEA. Results. Out of 685 first-time liver transplantations in a 10-year period, 327 received TEA, and 358 did not. The median Model of End-stage Liver Disease score was lower in the TEA group than in the non-TEA-group (9 versus 17, P < 0.001), and fewer patients were hospitalized preoperatively (16 versus 127, P < 0.001). The median international normalized ratio (1.1 versus 1.6, P < 0.001) and platelet count (190 versus 78, P < 0.001) were different between the TEA and non-TEA groups. There were no serious complications related to insertion or removal of the TEA catheters. Patients in the TEA group had less pain with a mean numeric rating scale at postoperative days 0–5 of 1.4 versus 1.8 (P = 0.008). Nearly 50% of the patients were prescribed opioids when discharged from hospital (non-TEA 154 versus TEA 158, P = 0.23), and there was no difference after 1 year (P = 0.718). Conclusions. Our report revealed very good pain control with both TEA and the non-TEA modality. TEA was without any serious complications like epidural hematoma or infection/abscess in selected liver transplant recipients without severe coagulopathy. Opioid prescription at hospital discharge and by 1-year follow-up did not differ between the groups.publishedVersio

Early detection of anastomotic leakage after pancreatoduodenectomy with microdialysis catheters: an observational Study

Background Microdialysis catheters can detect focal inflammation and ischemia, and thereby have a potential for early detection of anastomotic leakages after pancreatoduodenectomy. The aim was to investigate whether microdialysis catheters placed near the pancreaticojejunostomy can detect leakage earlier than the current standard of care. Methods Thirty-five patients with a median age 69 years were included. Two microdialysis catheters were placed at the end of surgery; one at the pancreaticojejunostomy, and one at the hepaticojejunostomy. Concentrations of glucose, lactate, pyruvate, and glycerol were analyzed hourly in the microdialysate during the first 24 h, and every 2–4 h thereafter. Results Seven patients with postoperative pancreatic fistulae (POPF) had significantly higher glycerol levels (P 400 μmol/L during the first 12 postoperative hours detected patients with POPF with a sensitivity of 100% and a specificity of 93% (P < 0.001). After 24 h, lactate and lactate-to-pyruvate ratio were significantly higher (P < 0.05) and glucose was significantly lower (P < 0.05) in patients with POPF. Conclusion High levels of glycerol in microdialysate was an early detector of POPF. The subsequent inflammation was detected as increase in lactate and lactate-to-pyruvate ratio and a decrease in glucose (NCT03627559).publishedVersio

European Living Donation and Public Health (EULID Project)

Donation from alive people has been growing strongly in the recent years, thanks to the advance in the field of organ transplantation and its success as a treatment to procure quality-adjusted life years for many patients with end–stage diseases. The choice of transplantation from a living donor (LD) offers some advantages compared to that for a deceased donor. However, it also carries disadvantages related to donor risks in terms of health and safety, and there are several controversial ethical aspects to be taken into account. There is no specific pronouncement of the European Union in relation to standards to quality and safety for the living donor process, and there is a great heterogeneity among European Countries legislation, ethical concern, and protection systems and donor´s data registries on the topic. The EULID project aims to establish European common standard framework regarding living donor issues to guarantee their health and safety thorough common practices and regulation

Immediate and long-term impact of the COVID-19 pandemic on delivery of surgical services

Background The ongoing pandemic is having a collateral health effect on delivery of surgical care to millions of patients. Very little is known about pandemic management and effects on other services, including delivery of surgery. Methods This was a scoping review of all available literature pertaining to COVID‐19 and surgery, using electronic databases, society websites, webinars and preprint repositories. Results Several perioperative guidelines have been issued within a short time. Many suggestions are contradictory and based on anecdotal data at best. As regions with the highest volume of operations per capita are being hit, an unprecedented number of operations are being cancelled or deferred. No major stakeholder seems to have considered how a pandemic deprives patients with a surgical condition of resources, with patients disproportionally affected owing to the nature of treatment (use of anaesthesia, operating rooms, protective equipment, physical invasion and need for perioperative care). No recommendations exist regarding how to reopen surgical delivery. The postpandemic evaluation and future planning should involve surgical services as an essential part to maintain appropriate surgical care for the population during an outbreak. Surgical delivery, owing to its cross‐cutting nature and synergistic effects on health systems at large, needs to be built into the WHO agenda for national health planning. Conclusion Patients are being deprived of surgical access, with uncertain loss of function and risk of adverse prognosis as a collateral effect of the pandemic. Surgical services need a contingency plan for maintaining surgical care in an ongoing or postpandemic phase.publishedVersio

Clinical and biochemical impact of vitamin B6 deficiency in primary sclerosing cholangitis before and after liver transplantation

Background and aims We previously demonstrated that people with primary sclerosing cholangitis (PSC) had reduced gut microbial capacity to produce active vitamin B6 (pyridoxal 5’-phosphate [PLP]), which corresponded to lower circulating PLP levels and poor outcomes. Here, we define the extent and biochemical and clinical impact of vitamin B6 deficiency in people with PSC from several centers before and after liver transplantation (LT). Methods We used targeted liquid chromatography-tandem mass spectrometry to measure B6 vitamers and B6-related metabolic changes in blood from geographically distinct cross-sectional cohorts totaling 373 people with PSC and 100 healthy controls to expand on our earlier findings. Furthermore, we included a longitudinal PSC cohort (n = 158) sampled prior to and serially after LT, and cohorts of people with inflammatory bowel disease (IBD) without PSC (n = 51) or with primary biliary cholangitis (PBC) (n = 100), as disease controls. We used Cox regression to measure the added value of PLP to predict outcomes before and after LT. Results In different cohorts, 17-38% of people with PSC had PLP levels below the biochemical definition of a vitamin B6 deficiency. The deficiency was more pronounced in PSC than in IBD without PSC and PBC. Reduced PLP was associated with dysregulation of PLP-dependent pathways. The low B6 status largely persisted after LT. Low PLP independently predicted reduced LT-free survival in both non-transplanted people with PSC and in transplant recipients with recurrent disease. Conclusions Low vitamin B6 status with associated metabolic dysregulation is a persistent feature of PSC. PLP was a strong prognostic biomarker for LT-free survival both in PSC and recurrent disease. Our findings suggest that vitamin B6 deficiency modifies the disease and provides a rationale for assessing B6 status and testing supplementation. Impact and implications We previously found that people with PSC had reduced gut microbial potential to produce essential nutrients. Across several cohorts, we find that the majority of people with PSC are either vitamin B6 deficient or have a marginal deficiency, which remains prevalent even after liver transplantation. Low vitamin B6 levels strongly associate with reduced liver transplantation-free survival as well as deficits in biochemical pathways dependent on vitamin B6, suggesting that the deficiency has a clinical impact on the disease. The results provide a rationale for measuring vitamin B6 and to investigate whether vitamin B6 supplementation or modification of the gut microbial community can help improve outcomes for people with PSC.publishedVersio

Liver transplantation for secondary liver tumours: The difficult balance between survival and recurrence

Assessing the balance between survival and recurrence after transplantation for secondary liver tumours should be based on the type of cancer in question. For neuroendocrine liver metastases, high recurrence rates are clearly related to reduced long-term survival. For colorectal liver metastases, experience to date indicates that pulmonary recurrence alone has a modest impact on survival outcomes. Further studies focusing on this group of patients will be important for the development of this field of transplant oncology. Liver transplantation for secondary liver tumours should be implemented in accordance with stringent transplant criteria and preferably in the context of prospective trials. Expansion of the donor pool by utilising extended criteria donors and partial liver transplantation could be considered for this indication

Hallmarks of postoperative liver regeneration: An updated insight on the regulatory mechanisms

Performance and advances in liver surgery makes remarkable progress of the understanding of liver regeneration. Liver regeneration after liver resection has been widely researched, and the underlying mechanism mostly concerns proliferation of hepatocytes and the influence by inflammation through activation of Kupffer cells and the other parenchymal cells, the second regenerative pathway by hepatic progenitor cells (HPCs), inducing angiogenesis, remodeling of a extracellular matrix (ECM), and termination mechanisms. New clinical surgeries and the updated multiomics analysis are exploiting the remarkable progress, especially in immune regulation and metabolic process of two emerging hallmarks. This review briefly represents a systemic outline of eight hallmarks, including hepatocyte proliferation, contribution of hepatic progenitor cells, inducing angiogenesis, reprogramming of the extracellular matrix, apoptosis and termination of proliferation, inflammation, immune and metabolic regulation, which are set as organizing characteristics of postoperative liver regeneration and future directions of refining treatment targets

The Potential Role of Liver Transplantation as a Treatment Option in Colorectal Liver Metastases

Liver resection is the only potentially curative treatment option in patients with liver metastases from colorectal cancer, but only about 20% of the patients are resectable. Liver transplantation of patients with unresectable liver metastases was attempted in the early era but it was abandoned due to poor survival. During the last decade, several case reports, a controlled pilot study, and a retrospective cohort study indicated that prolonged disease-free survival and overall survival can be obtained in a proportion of these patients. Strict selection criteria have not yet been well defined, but tumor load, response to chemotherapy, pretransplant carcinoembryonic antigen level, and time interval from resection of the primary tumor to transplant are all factors related to outcome. Carefully selected patients may obtain 5-year overall survival that approaches conventional indications for liver transplant. The scarcity of liver grafts is a significant problem, but this can possibly to some extent be addressed by use of extended criteria grafts and novel surgical techniques. There is an increasing interest in liver transplantation in these patients in the transplant community, and currently 4 clinical trials are active and are recruiting