Comparison of the reverse bevel versus Franseen type endoscopic ultrasound needle

BACKGROUNDReverse bevel (RB) needle is widely used for endoscopic ultrasound fine needle biopsy (EUS-FNB). A 3-plane symmetrical needle with Franseen geometry (FG) has recently become available. AIMTo compare the clinical efficacy of FG to that of RB needle.METHODSA retrospective cohort study of all adult patients who underwent EUS-FNB for solid and mixed lesions either with 22G RB needle or 22G FG needle between January 2016 and February 2019 was undertaken. All cytology slides were reviewed by an independent gastrointestinal cytopathologist blinded to the needle used and the initial cytology report. The primary and secondary outcomes were to assess the sample adequacy using Euro-cytology criteria and the number of cell clusters, respectively.RESULTSTwo hundred and twenty six procedures were included in the study. RB needle was used in 128 procedures and FG needle in 98 procedures. The baseline characteristics of both groups were comparable. On multivariable analysis, FG needle (P = 0.02) and location of the lesion (P < 0.01) were independently associated with adequate tissue. Further, the use of FG needle (P = 0.04) and the size of the lesion (P = 0.02) were independently associated with acquisition of increased number of cell clusters.CONCLUSIONFG needle is superior to RB needle in acquiring adequate tissue and attaining higher number of cell clusters for solid and mixed lesions

Role of Hepatocyte Senescence in the Activation of Hepatic Stellate Cells and Liver Fibrosis Progression

Hepatocyte senescence is associated with liver fibrosis. However, the possibility of a direct, causal relation between hepatocyte senescence and hepatic stellate cell (HSC) activation was the subject of this study. Liver biopsy specimens obtained from 50 patients with non-alcoholic fatty liver disease and a spectrum of liver fibrosis stages were stained for p16, αSMA, and picrosirius red (PSR). Primary human HSCs were cultured in conditioned media derived from senescent or control HepG2 cells. Expression of inflammatory and fibrogenic genes in HSCs cultured in conditioned media were studied using RT-PCR. ELISAs were undertaken to measure factors known to activate HSCs in the conditioned media from senescent and control HepG2 cells and serum samples from healthy volunteers or patients with biopsy-proven cirrhosis. There was a strong association between proportion of senescent hepatocytes and hepatic stellate cell activation. Both proportion of hepatocyte senescence and hepatic stellate cell activation were closely associated with fibrosis stage. Inflammatory and fibrogenic genes were up-regulated significantly in HSCs cultured in conditioned media from senescent HepG2 cells compared with control HepG2 cells. PDGF levels were significantly higher in the conditioned media from senescent hepatocytes than control HepG2-conditioned media, and in serum samples from patients with cirrhosis than healthy volunteers. In conclusion, this 'proof of concept' study revealed activation of human HSCs by media from senescent HepG2 cells, indicating direct involvement of factors secreted by senescent hepatocytes in liver fibrosis

Next-generation sequencing of pancreatic cyst wall specimens obtained using micro-forceps for improving diagnostic accuracy

Background and study aims: Pancreatic cysts are common incidental findings, with an estimated prevalence of 13-15% in imaging done for other reasons. Diagnosis often relies on collection of cyst fluid, but tissue sampling using micro-forceps may allow for a more reliable diagnosis and higher yield of DNA for next-generation sequencing (NGS). The primary aim was to assess the performance of NGS in identifying mucinous cyst. The secondary aims were to assess DNA yield between the cyst fluid and cyst wall tissue, complication rate and performance of conventional investigations. Patients and methods: 24 patients referred for endoscopic ultrasound were recruited. Biopsies were taken using micro-forceps and the AmpliSeq Cancer Hotspot panel was used for NGS, a PCR assay targeting several hotspots within 50 genes, including GNAS, KRAS and VHL. Results: The concentration of DNA extracted from 24 cyst wall samples was significantly higher than in the 9/24 available matched cyst fluid samples. The sensitivity, specificity and diagnostic accuracy of NGS for diagnosing mucinous cyst was 93%, 50% and 84%, standard of care -66.6%, 50% and 63.1% and for standard of care with NGS was 100%, 50% and 89.4% respectively. Cyst wall biopsy was able to diagnose 19/24 cysts (4 high risk, 7 intraductal papillary mucinous neoplasm, 4 cysts of mucinous origin and 4 benign). Conclusions: NGS data correlates well with histology and may aid in diagnosis and risk stratification of pancreatic cysts. Cyst wall biopsy performs well in diagnosing cysts but was inadequate in 5/24 patients

Incidence and prevalence of venous thromboembolism in chronic liver disease: a systematic review and meta-analysis

Background and Aims: Historically, bleeding was thought to be a frequent and fatal complication of liver disease. However, thrombosis due to coagulation disorders in cirrhosis remains a real risk. We aim to systematically analyse published articles to evaluate epidemiology of venous thromboembolism (VTE) in chronic liver disease (CLD). Method: Electronic search was conducted on Ovid Medline, EMBASE and Scopus from inception to November 2021 to identify studies presenting epidemiology VTE (deep vein thrombosis and pulmonary embolism) in CLD in inpatients and/or community settings. Random-effects meta-analysis was performed to determine pooled per-year cumulative incidence, incidence rate and prevalence. Heterogeneity was measured by I² test, and, potential sources of heterogeneity by meta-regression and sensitivity analysis. PROSPERO registration-CRD42021239117. Results: Twenty-nine studies comprising 19,157,018 participants were included, of which 15,2049 (0.79%) had VTE. None of included the studies were done in the community. In hospitalised patients with CLD: pooled cumulative incidence of VTE was 1.07% (95%CI 0.80,1.38) per-year, incidence rate was 157.15 (95%CI 14.74,445.29) per 10,000 person-years, and period prevalence was 1.10% (95%CI 0.85,1.38) per year. There was significant heterogeneity and publication bias. Pooled relative risk (RR) of studies reporting incidence rate was 2.11 (95%CI 1.35,3.31). CLD patients (n=1644), who did not receive pharmacological prophylaxis were at 2.78 times (95% CI 1.11, 6.98) increased risk of VTE compared to those receiving prophylaxis. Conclusion: Hospitalised patients with CLD may be at an increased risk of VTE . For every 1000 hospitalised patients with CLD ten have new, and eleven have pre-existing diagnoses of VTE per-year

Estimating the clinical prevalence of Wilson’s disease in the UK

Background and AimThe clinical prevalence of Wilson’s disease (WD) in the UK remains unknown. The estimated genetic prevalence in the UK, 142/million, is higher than the clinical prevalence (15/million) reported in other European studies. The aim of this study was to estimate the clinical prevalence of WD utilising readily available laboratory and clinical data.MethodPatients with WD who attended Nottingham University Hospital NHS Trust (NUH) between 2011 and 2018 were identified using multiple sources of case ascertainment: serum ceruloplasmin, 24-hour urinary copper, ‘Wilson’ in liver biopsy report, hospital prescription for penicillamine/trientine/zinc and admission coded with ICD-10 Code E83.0 (disorder of copper metabolism). Potential cases were identified using the Leipzig score, diagnosis was confirmed in hospital records and the point prevalence was calculated using the Office for National Statistics mid-2017 population estimates.ResultsA total of 1,794 patients were identified from ≥1 source; 19 patients had WD, of which 11 were from within the study catchment area and alive at the time of point prevalence estimation. Twentynine patients had Leipzig score ≥2 without a diagnosis of WD, but none had WD on screening (n=16). The overall prevalence of WD was 15.5/million; males 16.9/million and females 14.1/million.ConclusionThis is the first UK population-based study of WD clinical prevalence. This is lower than the UK genetic prevalence, but comparable to European clinical prevalence. The case ascertainment approach used in this study may be a cost-effective, and similar practises could be adopted nationally

Next-generation sequencing of pancreatic cyst wall specimens obtained using Moray micro-forceps for improving diagnostic accuracy

Background and study aims Pancreatic cysts are common incidental findings, with an estimated prevalence of 13-15% in imaging done for other reasons. It is difficult to identify cysts with malignant potential. Diagnosis often relies on collection of cyst fluid, but tissue sampling using micro-forceps may allow for a more reliable diagnosis and higher yield of DNA for next-generation sequencing (NGS).Patients and methods 24 patients referred for endoscopic ultrasound were recruited. Biopsies were taken using micro-forceps and the AmpliSeq Cancer Hotspot panel was used for NGS, a PCR assay targeting several hotspots within 50 genes, including GNAS, KRAS and VHL.Results The concentration of DNA extracted from 24 cyst wall samples was significantly higher than in the 9/24 available matched cyst fluid samples. Cyst wall biopsy was able to diagnose 19/24 cysts (5 high risk, 6 intraductal papillary mucinous neoplasm and 4 benign). The sensitivity, specificity and diagnostic accuracy for standard of care was 66.6%, 50% and 63.1% respectively and for standard of care with NGS was 100%, 50% and 89.4% respectively.Conclusions Cyst wall biopsy performs well in diagnosing cysts but was inadequate in 5/24 patients. NGS data correlates well with histology and may aid in diagnosis and risk stratification of pancreatic cysts

Donor outcomes in anonymous live liver donation

BackgroundDeath rates on liver transplant waiting lists range from 5%-25%. Herein, we report a unique experience with 50 anonymous persons who volunteered to address this gap by offering to donate part of their liver to a recipient with whom they had no biological connection or prior relationship (A-LLD).MethodsCandidates were screened to confirm excellent physical, mental, social, and financial health. Demographics and surgical outcomes were analyzed. Qualitative interviews after donation examined motivation and experiences. Validated self-reported questionnaires assessed personality traits and psychological impact.Results50 A-LLD liver transplants (LT) were performed between 2005 and 2017. Most donors had a university education, a middle-class income, and a history of prior altruism. Half were women. Median age was 38.5 years (range 20-59 yrs.). Thirty-three (70%) learned about this opportunity through public or social media. Saving a life, helping others, generativity, and reciprocity for past generosity were motivators. Social, financial, healthcare, and legal supports in Canada were identified as facilitators. A-LLD identified most with the personality traits of agreeableness and conscientiousness. The median hospital stay was six days. There was one Dindo-Clavien Grade 3 complication that completely resolved. One-year recipient survival was 91% in 22 adults and 97% in 28 children. No A-LLD reported regretting their decision.ConclusionsThis is the first and only report of the motivations and facilitators of A-LLD in a large cohort. With rigorous protocols, outcomes are excellent. A-LLD has significant potential to reduce the gap between transplant organ demand and availability

The impact of preexisting and post-transplant diabetes mellitus on outcomes following liver transplantation

Background: Diabetes mellitus (DM) is said to adversely affect transplant outcomes. The aim of this study was to investigate the impact of pre-existing and post-transplant DM on liver transplant (LT) recipients.Method: A single centre retrospective analysis of prospectively collected data of LT recipients (1990–2015) was undertaken.Results: Of the 2,209 patients, 13% (n=298) had Pre-DM, 16% (n=362) developed PTDM, 5% (n=118) developed transient hyperglycemia (t-HG) post-LT, and 65% (n=1,431) never developed DM (no DM). Baseline clinical characteristics of patients with PTDM was similar to that of patients with pre-DM. Incidence of PTDM peaked during first-year (87%) and plateaued thereafter. On multivariate analysis (Bonferroni-corrected), non-alcoholic fatty liver disease and the use of Tacrolimus and Sirolimus use were independently associated with PTDM development. Both Pre-DM and PTDM patients had satisfactory and comparable glycaemic control throughout the follow-up period. Those who developed t-HG seems to have a unique characteristic compared to others. Overall, 9%, 5%, and 8% developed end-stage renal disease (ESRD), major cardiovascular event (mCVE), and de novo cancer, respectively. Both Pre-DM and PTDM did not adversely affect patient survival, re-LT, or de novo cancer. The risks of ESRD and mCVE were significantly higher in patients with Pre-DM followed by PTDM and no DM.Conclusions: In this largest non-registry study, patients with pre-DM and PTDM share similar baseline clinical characteristics. Pre-DM increases the risk of ESRD and mCVE; however, patient survival was comparable to those with PTDM and without diabetes. Understanding the impact of PTDM would need prolonged follow-up