Introduction
Prehabilitation prior to major surgery has increased in popularity over recent years and aims to improve pre-operative conditioning of patients to improve post-operative outcomes. The ...beneficial effect of such protocols is not well established with conflicting results reported. This review aimed to assess the effect of prehabilitation on post-operative outcome after major abdominal surgery.
Methods
EMBASE, Medline, PubMed and the Cochrane database were searched in August 2018 for trials comparing outcomes of patients undergoing prehabilitation involving prescribed respiratory and exercise interventions prior to abdominal surgery. Study characteristics, overall and pulmonary morbidity, length of stay (LOS), maximum inspiratory pressure and change in six-minute walking test (6MWT) distance were obtained. The primary outcome was post-operative overall morbidity within 30 days. Dichotomous data were analysed by fixed or random effects odds ratio. Continuous data were analysed with weighted mean difference.
Results
Fifteen RCTs were included in the analysis with 457 prehabilitation patients and 450 control group patients. A significant reduction in overall (OR 0.63 95% CI 0.46–0.87
I
2
34%,
p
= 0.005) and pulmonary morbidity (OR 0.4 95% CI 0.23–0.68,
I
2
= 0%,
p
= 0.0007) was observed in the prehabilitation group. No significant difference in LOS (WMD −2.39 95% CI −4.86 to 0.08
I
2
= 0%,
p
= 0.06) or change in 6MWT distance (WMD 9.06 95% CI −35.68, 53.81
I
2
= 88%,
p
= 0.69) was observed.
Conclusions
Prehabilitation can reduce overall and pulmonary morbidity following surgery and could be utilised routinely. The precise protocol of prehabilitation has not been completely established. Further work is required to tailor optimal prehabilitation protocols for specific operative procedures.
Livers from controlled donation after circulatory death (DCD) donors suffer a higher incidence of nonfunction, poor function, and ischemic cholangiopathy. In situ normothermic regional perfusion ...(NRP) restores a blood supply to the abdominal organs after death using an extracorporeal circulation for a limited period before organ recovery. We undertook a retrospective analysis to evaluate whether NRP was associated with improved outcomes of livers from DCD donors. NRP was performed on 70 DCD donors from whom 43 livers were transplanted. These were compared with 187 non-NRP DCD donor livers transplanted at the same two UK centers in the same period. The use of NRP was associated with a reduction in early allograft dysfunction (12% for NRP vs. 32% for non-NRP livers, P = .0076), 30-day graft loss (2% NRP livers vs. 12% non-NRP livers, P = .0559), freedom from ischemic cholangiopathy (0% vs. 27% for non-NRP livers, P < .0001), and fewer anastomotic strictures (7% vs. 27% non-NRP, P = .0041). After adjusting for other factors in a multivariable analysis, NRP remained significantly associated with freedom from ischemic cholangiopathy (P < .0001). These data suggest that NRP during organ recovery from DCD donors leads to superior liver outcomes compared to conventional organ recovery.
Human liver cancer research currently lacks in vitro models that can faithfully recapitulate the pathophysiology of the original tumor. We recently described a novel, near-physiological organoid ...culture system, wherein primary human healthy liver cells form long-term expanding organoids that retain liver tissue function and genetic stability. Here we extend this culture system to the propagation of primary liver cancer (PLC) organoids from three of the most common PLC subtypes: hepatocellular carcinoma (HCC), cholangiocarcinoma (CC) and combined HCC/CC (CHC) tumors. PLC-derived organoid cultures preserve the histological architecture, gene expression and genomic landscape of the original tumor, allowing for discrimination between different tumor tissues and subtypes, even after long-term expansion in culture in the same medium conditions. Xenograft studies demonstrate that the tumorogenic potential, histological features and metastatic properties of PLC-derived organoids are preserved in vivo. PLC-derived organoids are amenable for biomarker identification and drug-screening testing and led to the identification of the ERK inhibitor SCH772984 as a potential therapeutic agent for primary liver cancer. We thus demonstrate the wide-ranging biomedical utilities of PLC-derived organoid models in furthering the understanding of liver cancer biology and in developing personalized-medicine approaches for the disease.
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•An increasing proportion of patients are being transplanted for non-alcoholic steatohepatitis (NASH) in Europe.•Hepatocellular carcinoma was more common in patients transplanted with ...NASH.•Survival in recipients with NASH is comparable to that of other disease indications.•Age, BMI, and advanced liver disease predicted poorer outcomes in NASH recipients.
Little is known about outcomes of liver transplantation for patients with non-alcoholic steatohepatitis (NASH). We aimed to determine the frequency and outcomes of liver transplantation for patients with NASH in Europe and identify prognostic factors.
We analysed data from patients transplanted for end-stage liver disease between January 2002 and December 2016 using the European Liver Transplant Registry database. We compared data between patients with NASH versus other aetiologies. The principle endpoints were patient and overall allograft survival.
Among 68,950 adults undergoing first liver transplantation, 4.0% were transplanted for NASH – an increase from 1.2% in 2002 to 8.4% in 2016. A greater proportion of patients transplanted for NASH (39.1%) had hepatocellular carcinoma (HCC) than non-NASH patients (28.9%, p <0.001). NASH was not significantly associated with survival of patients (hazard ratio HR 1.02, p = 0.713) or grafts (HR 0.99; p = 0.815) after accounting for available recipient and donor variables. Infection (24.0%) and cardio/cerebrovascular complications (5.3%) were the commonest causes of death in patients with NASH without HCC. Increasing recipient age (61–65 years: HR 2.07, p <0.001; >65: HR 1.72, p = 0.017), elevated model for end-stage liver disease score (>23: HR 1.48, p = 0.048) and low (<18.5 kg/m2: HR 4.29, p = 0.048) or high (>40 kg/m2: HR 1.96, p = 0.012) recipient body mass index independently predicted death in patients transplanted for NASH without HCC. Data must be interpreted in the context of absent recognised confounders, such as pre-morbid metabolic risk factors.
The number and proportion of liver transplants performed for NASH in Europe has increased from 2002 through 2016. HCC was more common in patients transplanted with NASH. Survival of patients and grafts in patients with NASH is comparable to that of other disease indications.
The prevalence of non-alcoholic fatty liver disease has increased dramatically in parallel with the worldwide increase in obesity and diabetes. Its progressive form, non-alcoholic steatohepatitis, is a growing indication for liver transplantation in Europe, with good overall outcomes reported. However, careful risk factor assessment is required to maintain favourable post-transplant outcomes in patients with non-alcoholic steatohepatitis.
Abstract Background Enhanced recovery after surgery (ERAS) programmes aim to improve postoperative outcomes. They are being utilized increasingly in hepatic surgery. This review aims to evaluate the ...impact of ERAS programmes on outcomes following liver surgery. Methods EMBASE, MEDLINE, PubMed and the Cochrane Database were searched for trials comparing outcomes in patients undergoing liver surgery utilizing ERAS principles with those in patients receiving conventional care. The primary outcome was occurrence of postoperative complications within 30 days. Secondary outcomes included length of stay (LoS), functional recovery and adherence to ERAS protocols. Results Nine articles were included in the review, of which two were randomized controlled trials (RCTs). Overall complication rates were 25.0% (range: 11.5–46.4%) in ERAS patients, and 31.0% (range: 11.8–46.2%) in conventional care patients. Significantly reduced overall complication rates following ERAS care were demonstrated by a meta-analysis of the data reported in the two RCTs (odds ratio: 0.49, 95% confidence interval 0.28–0.84; P = 0.01) The median LoS reported by the studies was 5.0 days (range: 2.5–7.0 days) in ERAS patients, and 7.5 days (range: 3.0–11.0 days) in non-ERAS patients. Recovery milestones, when reported, were improved following ERAS care. Conclusions The adoption of ERAS protocols improves morbidity and LoS following liver surgery. Future ERAS programmes should accommodate the unique requirements of liver surgery in order to optimize postoperative outcomes.
Abstract Background Enhanced recovery after surgery (ERAS) is a well-established pathway of perioperative care in surgery in an increasing number of specialties. To implement protocols and maintain ...high levels of compliance, continued support from care providers and patients is vital. This survey aimed to assess the perceptions of care providers and patients of the relevance and importance of the ERAS targets and strategies. Materials and methods Pre- and post-operative surveys were completed by patients who underwent major hepatic, colorectal, or oesophagogastric surgery in three major centers in Scotland, Norway, and The Netherlands. Anonymous web-based and article surveys were also sent to surgeons, anesthetists, and nurses experienced in delivering enhanced recovery protocols. Each questionnaire asked the responder to rate a selection of enhanced recovery targets and strategies in terms of perceived importance. Results One hundred nine patients and 57 care providers completed the preoperative survey. Overall, both patients and care providers rated the majority of items as important and supported ERAS principles. Freedom from nausea (median, 10; interquartile range IQR, 8–10) and pain at rest (median, 10; IQR, 8–10) were the care components rated the highest by both patients and care providers. Early return of bowel function (median, 7; IQR, 5–8) and avoiding preanesthetic sedation (median, 6; IQR, 3.75–8) were scored the lowest by care providers. Conclusions ERAS principles are supported by both patients and care providers. This is important when attempting to implement and maintain an ERAS program. Controversies still remain regarding the relative importance of individual ERAS components.
Background and Aims
Genome‐wide association studies (GWAS) have identified several risk loci for gallstone disease. As with most polygenic traits, it is likely that many genetic determinants are ...undiscovered. The aim of this study was to identify genetic variants that represent new targets for gallstone research and treatment.
Approach and Results
We performed a GWAS of 28,627 gallstone cases and 348,373 controls in the UK Biobank, replicated findings in a Scottish cohort (1089 cases, 5228 controls), and conducted a GWA meta‐analysis (43,639 cases, 506,798 controls) with the FinnGen cohort. We assessed pathway enrichment using gene‐based then gene‐set analysis and tissue expression of identified genes in Genotype‐Tissue Expression project data. We constructed a polygenic risk score (PRS) and evaluated phenotypic traits associated with the score. Seventy‐five risk loci were identified (p < 5 × 10−8), of which 46 were new. Pathway enrichment revealed associations with lipid homeostasis, glucuronidation, phospholipid metabolism, and gastrointestinal motility. Anoctamin 1 (ANO1) and transmembrane Protein 147 (TMEM147), both in novel, replicated loci, are expressed in the gallbladder and gastrointestinal tract. Both regulate gastrointestinal motility. The gallstone risk allele rs7599‐A leads to suppression of hepatic TMEM147 expression, suggesting that the protein protects against gallstone formation. The highest decile of the PRS demonstrated a 6‐fold increased odds of gallstones compared with the lowest decile. The PRS was strongly associated with increased body mass index, serum liver enzymes, and C‐reactive protein concentrations, and decreased lipoprotein cholesterol concentrations.
Conclusions
This GWAS demonstrates the polygenic nature of gallstone risk and identifies 46 novel susceptibility loci. We implicate genes influencing gastrointestinal motility in the pathogenesis of gallstones.
Background & Aims Liver regeneration requires functional liver macrophages, which provide an immune barrier that is compromised after liver injury. The numbers of liver macrophages are controlled by ...macrophage colony-stimulating factor (CSF1). We examined the prognostic significance of the serum level of CSF1 in patients with acute liver injury and studied its effects in mice. Methods We measured levels of CSF1 in serum samples collected from 55 patients who underwent partial hepatectomy at the Royal Infirmary Edinburgh between December 2012 and October 2013, as well as from 78 patients with acetaminophen-induced acute liver failure admitted to the Royal Infirmary Edinburgh or the University of Kansas Medical Centre. We studied the effects of increased levels of CSF1 in uninjured mice that express wild-type CSF1 receptor or a constitutive or inducible CSF1-receptor reporter, as well as in chemokine receptor 2 (Ccr2)-/- mice; we performed fate-tracing experiments using bone marrow chimeras. We administered CSF1-Fc (fragment, crystallizable) to mice after partial hepatectomy and acetaminophen intoxication, and measured regenerative parameters and innate immunity by clearance of fluorescent microbeads and bacterial particles. Results Serum levels of CSF1 increased in patients undergoing liver surgery in proportion to the extent of liver resected. In patients with acetaminophen-induced acute liver failure, a low serum level of CSF1 was associated with increased mortality. In mice, administration of CSF1-Fc promoted hepatic macrophage accumulation via proliferation of resident macrophages and recruitment of monocytes. CSF1-Fc also promoted transdifferentiation of infiltrating monocytes into cells with a hepatic macrophage phenotype. CSF1-Fc increased innate immunity in mice after partial hepatectomy or acetaminophen-induced injury, with resident hepatic macrophage as the main effector cells. Conclusions Serum CSF1 appears to be a prognostic marker for patients with acute liver injury. CSF1 might be developed as a therapeutic agent to restore innate immune function after liver injury.
Background
Enhanced Recovery After Surgery (ERAS) has been widely applied in liver surgery since the publication of the first ERAS guidelines in 2016. The aim of the present article was to update the ...ERAS guidelines in liver surgery using a modified Delphi method based on a systematic review of the literature.
Methods
A systematic literature review was performed using MEDLINE/PubMed, Embase, and the Cochrane Library. A modified Delphi method including 15 international experts was used. Consensus was judged to be reached when >80% of the experts agreed on the recommended items. Recommendations were based on the Grading of Recommendations, Assessment, Development and Evaluations system.
Results
A total of 7541 manuscripts were screened, and 240 articles were finally included. Twenty-five recommendation items were elaborated. All of them obtained consensus (>80% agreement) after 3 Delphi rounds. Nine items (36%) had a high level of evidence and 16 (64%) a strong recommendation grade. Compared to the first ERAS guidelines published, 3 novel items were introduced: prehabilitation in high-risk patients, preoperative biliary drainage in cholestatic liver, and preoperative smoking and alcohol cessation at least 4 weeks before hepatectomy.
Conclusions
These guidelines based on the best available evidence allow standardization of the perioperative management of patients undergoing liver surgery. Specific studies on hepatectomy in cirrhotic patients following an ERAS program are still needed.
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