Mark Wilkinson

Are we meeting the standards set for endoscopy? Results of a large-scale prospective survey of endoscopic retrograde cholangio-pancreatograph practice

Objective: To examine endoscopic retrograde cholangio-pancreatography (ERCP) services and training in the UK. Design: Prospective multicentre survey. Setting: Five regions of England. Participants: Hospitals with an ERCP unit. Outcome measures: Adherence to published guidelines, technical success rates, complications and mortality. Results: Organisation questionnaires were returned by 76 of 81 (94%) units. Personal questionnaires were returned by 190 of 213 (89%) ERCP endoscopists and 74 of 91 (81%) ERCP trainees, of whom 45 (61%) reported participation in <50 ERCPs per annum. In all, 66 of 81 (81%) units collected prospective data on 5264 ERCPs, over a mean period of 195 days. Oximetry was used by all units, blood pressure monitoring by 47 of 66 (71%) and ECG monitoring by 37 of 66 (56%) units; 1484 of 4521 (33%) patients were given >5 mg of midalozam. Prothrombin time was recorded in 4539 of 5264 (86%) procedures. Antibiotics were given in 1021 of 1412 (72%) cases, where indicated. Patients’ American Society of Anesthesiology (ASA) scores were 3–5 in 670 of 5264 (12.7%) ERCPs, and 4932 of 5264 (94%) ERCPs were scheduled with therapeutic intent. In total, 140 of 182 (77%) trained endoscopists demonstrated a cannulation rate ⩾80%. The recorded cannulation rate among senior trainees (with an experience of >200 ERCPs) was 222/338 (66%). Completion of intended treatment was done in 3707 of 5264 (70.4%) ERCPs; 268 of 5264 (5.1%) procedures resulted in a complication. Procedure-related mortality was 21/5264 (0.4%). Mortality correlated with ASA score. Conclusion: Most ERCPs in the UK are performed on low-risk patients with therapeutic intent. Complication rates compare favourably with those reported internationally. However, quality suffers because there are too many trainees in too many low-volume ERCP centres.

Expression of MUC1 and MUC2 mucin gene products in Barrett's metaplasia, dysplasia and adenocarcinoma : an immunopathological study with clinical correlation

Changes in the histochemical characteristics of the surface epithelial mucins is the hallmark of Barretts metaplasia. The study investigated the pattern of expression of MUC1 and MUC2 mucin gene products in Barretts metaplasia, dysplasia and adenocarcinoma as possible indicators of increased malignant potential.

New therapies for chronic hepatitis C infection: a systematic review of evidence from clinical trials.

Introduction:u2002 Hepatitis C virus (HCV) affects approximately 3% of the world population. The current standard of care for treatment of HCV is a combination of pegylated interferon and ribavirin. Approximately 10% of patients will stop treatment and 30% of patients require dose reduction because of side effects. For genotype 1 HCV‐infected patients, only 40% of patients will achieve undetectable viral load 26u2003weeks posttreatment.

Estrogen and androgen regulation of sex hormone binding globulin secretion by a human liver cell line

Both estrogens and androgens have been shown to stimulate sex hormone binding globulin (SHBG) secretion in vitro in the hepatocellular carcinoma cell line, Hep G2, in contrast to the expected inhibition by androgens from in vivo studies. However, such in vitro stimulation was only demonstrated at high steroid doses, generally in serum-containing medium, with added Phenol Red. In the present study, Hep G2 cells were grown in serum-free medium, without Phenol Red, under the influence of testosterone (T) (0, 0.5-500 nM) and ethinyl estradiol (EE2) (0, 50 pM-500 nM). Levels of secreted SHBG and albumin were correlated with androgen receptors in cytosolic (ARc) and nuclear (ARn) fractions and with DNA levels. In the presence of increasing T levels, SHBG levels fell to 39% of control values at 5 nM T (P = 0.047), rising to 97% of control at 500 nM. Conversely, incubation with EE2 produced a rise in SHBG secretion of more than 100% at 0.5 nM (P less than 0.02) which was sustained to 50 nM (P less than 0.005). DNA levels did not change with the addition of testosterone or EE2, with the exception of a 15% reduction at 5 nM EE2 (P less than 0.05). Albumin levels in the medium were not significantly altered by either steroid. However, in response to T, androgen receptor (AR) levels were reduced in cytosolic (42% of control) and nuclear (22%) fractions at 5 nM, and these changes in ARc and ARn correlated with SHBG levels over the range of T concentrations (P = 0.04 and P = 0.017, respectively). Nuclear estrogen receptor (ER) increased over 10-fold at 5 and 50 pM EE2 (P less than 0.001) and maintained 50 nM (P less than 0.001). Cytosolic ER was reduced at 0.5 and 5 nM but recovered at 50 nM, correlating with SHBG levels (P less than 0.001). These findings are consistent with the hypothesis that estrogens and androgens regulate SHBG synthesis in man by direct, specific, probably receptor-mediated effects on hepatocytes. Hep G2 cells grown in serum-free medium are a suitable experimental system for further study of this phenomenon.

Evaluation of the genetic overlap between osteoarthritis with body mass index and height using genome-wide association scan data

Objectives Obesity as measured by body mass index (BMI) is one of the major risk factors for osteoarthritis. In addition, genetic overlap has been reported between osteoarthritis and normal adult height variation. We investigated whether this relationship is due to a shared genetic aetiology on a genome-wide scale. Methods We compared genetic association summary statistics (effect size, p value) for BMI and height from the GIANT consortium genome-wide association study (GWAS) with genetic association summary statistics from the arcOGEN consortium osteoarthritis GWAS. Significance was evaluated by permutation. Replication of osteoarthritis association of the highlighted signals was investigated in an independent dataset. Phenotypic information of height and BMI was accounted for in a separate analysis using osteoarthritis-free controls. Results We found significant overlap between osteoarthritis and height (p=3.3×10−5 for signals with p≤0.05) when the GIANT and arcOGEN GWAS were compared. For signals with p≤0.001 we found 17 shared signals between osteoarthritis and height and four between osteoarthritis and BMI. However, only one of the height or BMI signals that had shown evidence of association with osteoarthritis in the arcOGEN GWAS was also associated with osteoarthritis in the independent dataset: rs12149832, within the FTO gene (combined p=2.3×10−5). As expected, this signal was attenuated when we adjusted for BMI. Conclusions We found a significant excess of shared signals between both osteoarthritis and height and osteoarthritis and BMI, suggestive of a common genetic aetiology. However, only one signal showed association with osteoarthritis when followed up in a new dataset.

What predicts failed cannulation and therapy at ERCP? Results of a large-scale multicenter analysis

UNLABELLEDnSTUDY BACKGROUND AND AIMS: Predicting outcome at endoscopic retrograde cholangiopancreatography (ERCP) remains difficult. Our aim was to identify the risk factors for failed ERCP.nnnPATIENTS AND METHODSnA prospective multicenter study of ERCP was performed in 66 hospitals across England. Data on 4561 patients were collected using a structured questionnaire completed at the time of ERCP.nnnRESULTSnIn total 3209 patients had not had an ERCP prior to the study period. Considering their first ever ERCP, 2683 (84 %) were successfully cannulated, 2241(70 %) had all intended therapy completed, 360 (11 %) had some intended therapy completed, and 608 (19 %) were considered to have had a failed procedure. For first ever ERCP, factors associated with incomplete procedure (odds ratio and 95 % confidence interval) were: Billroth surgery (9.2, 3.2 - 26.7), precutting (2.0, 1.6 - 2.7), common bile duct (CBD) stone size and number (3.2, 2.1 - 4.8 for multiple, large stones), interventions in the pancreatic duct (3.4, 1.6 - 7.0), and CBD stenting (2.8, 2.2 - 3.5). Analysis of the 1352 patients who had undergone an ERCP prior to the study period indicated previous failed ERCP was also predictive of incomplete therapy (1.5, 1.1 - 2.1). The modified Schutz score correlated with ERCP completion, as did the Morriston score, even when modified to include only variables measurable before the procedure.nnnCONCLUSIONnThis study confirms that patient- and procedure-based variables are key predictors of technical success and validates current methods of rating ERCP difficulty. Of note, a correlation between outcome and institutional factors, such as unit and endoscopist caseload, was not demonstrated.

The substitution of endoscopic ultrasound for endoscopic retrograde cholangio-pancreatography: implications for service development and training.

Objectives Choledocholithiasis and other benign conditions of the biliary tree are difficult to define clinically. Endoscopic retrograde cholangio-pancreatography (ERCP) is increasingly being replaced as the investigation of choice by other imaging modalities. The aim of this study was to measure the impact of substituting endoscopic ultrasound (EUS) for ERCP in terms of case throughput and the proportion of therapeutic ERCPs performed. Methods Over a 12-month period, cases with a low/medium likelihood for biliary pathology were triaged to EUS rather than ERCP. Data were collected on the proportion of ERCPs performed with diagnostic or therapeutic intent and compared with data from the preceding 12-month period. Results In the 12 months to April 2001, 518 cases were referred for ERCP; 140 underwent EUS and 378 underwent ERCP. The proportions of diagnostic and therapeutic ERCP were 14% and 86%, respectively. Benign biliary disease represented 33% of all referrals for EUS, and calculi were identified in 6% of these cases. During the preceding year, 637 ERCPs were performed. The proportion of diagnostic (33%) and therapeutic (67%) cases differed from the index year (P < 0.001). Conclusions The substitution of EUS for ERCP results in significant quantitative and qualitative change to ERCP practice, which has direct consequences for training and service development.

A re-assessment of the epidemiology and patient characteristics of hepatitis D virus infection in inner city London

OBJECTIVESnTo re-assess the prevalence and patient characteristics of hepatitis D virus (HDV) infection among hepatitis B patients in inner city London.nnnMETHODSnAll hepatitis B patients attending clinics over a 52 months period were tested for HDV antibody. All reactive samples were also tested for anti-HDV IgM and RNA. The characteristics of HDV seronegative patients first seen in the calendar year 2008 were compared with all HDV seropositive patients in the cohort.nnnRESULTSnOf 1048 hepatitis B patients, 11 had equivocal anti-HDV serology (1%) and 22 were HDV seropositive (2.1%, 95%CI 1.39-3.16%); 12 were anti-HDV IgM positive and 15 HDV RNA positive. No patient with equivocal anti-HDV serology had detectable HDV RNA. Five HDV seropositive patients were intravenous drug users (22.7%); 17/22 were from abroad with 11/22 (50%) from sub-Saharan Africa. HDV seropositive patients had poorer laboratory parameters and were more likely to have evidence of cirrhosis. Triple infected (HIV/HBV/HDV) patients were also more likely to have cirrhosis than HIV/HBV dually infected patients.nnnCONCLUSIONSnThe prevalence of HDV in hepatitis B patients in inner city London was about 2%. The role of migration from endemic countries should be recognised.

Post-vaccination serological test results of infants at risk of perinatal transmission of hepatitis B using an intensified follow-up programme in a London centre.

Immunisation of infants born to hepatitis B virus (HBV) infected mothers is an important public health measure to prevent mother-to-child transmission of HBV. Post-vaccination serological tests (PVST) inform the success of the infant HBV immunisation programme and identify infected infants. Previous studies suggested that the rates of PVST in the UK programme were unsatisfactory. We introduced an intensified local follow-up programme and offered an earlier PVST 2-3 months after the third vaccination at age 4-5 months. Of 219 infants born between 2009 and 2011, 193 infants (88.1%) had at least one PVST: 145 (66.2%) early; 94 (42.9%) standard; 46 (21.0%) both and 26 (11.9%) never tested. Twenty-four infants were identified as high risk for mother-to-child transmission according to national criteria and received both hepatitis B immunoglobulin (HBIG) and hepatitis B vaccine at birth. These infants had a significantly lower hepatitis B surface antibody (anti-HBs) levels at early PVST compared to the lower risk group who received hepatitis B vaccine only (median of 59 vs. 376 mIU/ml, P=0.006). None of the infants tested were infected with hepatitis B. This study illustrates that the rate of PVST can be improved by using an intensified follow-up programme offering an early PVST. The significantly lower anti-HBs levels in the HBIG subgroup is of concern as this group of infants is already at higher risk for acquiring HBV infection. Infants with poor antibody responses can be identified by an early PVST and offered a timely extra booster dose.

Measurement of androgen receptor expression in adult liver, fetal liver, and Hep-G2 cells by the polymerase chain reaction.

Hepatocellular carcinoma is the most commonly fatal malignant tumour worldwide. The role of androgen receptors, which have been found in hepatocellular carcinoma, is controversial. Sequence specific polymerase chain reaction (PCR) was used to quantify, for the first time, the expression of androgen receptor in four adult liver biopsy specimens (HL-A to HL-D), fetal liver, and Hep-G2 cells. The measurement of androgen receptor is expressed as a ratio (androgen receptor: beta-actin) of the value of androgen receptor to the value of a control gene, beta-actin. The value of the androgen receptor: beta-actin ratios for HL-A, HL-B, HL-C, HL-D, fetal liver, and Hep-G2 were 0.37, 0.86, 0.37, 0.44, 0.87, and 0.66 respectively. To verify sequence specific amplification of the androgen receptor, the PCR androgen receptor fragment was sequenced. The resultant sequence data for both strands of the double stranded PCR androgen receptor fragment had 100% similarity with the published androgen receptor mRNA sequence (complete codons).