Martin Lombard

Guidelines on the management of common bile duct stones (CBDS)

The last 30 years have seen major developments in the management of gallstone-related disease, which in the United States alone costs over 6 billion dollars per annum to treat. Endoscopic retrograde cholangiopancreatography (ERCP) has become a widely available and routine procedure, whilst open cholecystectomy has largely been replaced by a laparoscopic approach, which may or may not include laparoscopic exploration of the common bile duct (LCBDE). In addition, new imaging techniques such as magnetic resonance cholangiography (MR) and endoscopic ultrasound (EUS) offer the opportunity to accurately visualise the biliary system without instrumentation of the ducts. As a consequence clinicians are now faced with a number of potentially valid options for managing patients with suspected CBDS. It is with this in mind that the following guidelines have been written.

Addressing liver disease in the UK: a blueprint for attaining excellence in health care and reducing premature mortality from lifestyle issues of excess consumption of alcohol, obesity, and viral hepatitis.

Liver disease in the UK stands out as the one glaring exception to the vast improvements made during the past 30 years in health and life expectancy for chronic disorders such as stroke, heart disease, and many cancers. Mortality rates have increased 400% since 1970, and in people younger than 65 years have risen by almost five-times. Liver disease constitutes the third commonest cause of premature death in the UK and the rate of increase of liver disease is substantially higher in the UK than other countries in western Europe. More than 1 million admissions to hospital per year are the result of alcohol-related disorders, and both the number of admissions and the increase in mortality closely parallel the rise in alcohol consumption in the UK during the past three decades. The aim of this Commission is to provide the strongest evidence base through involvement of experts from a wide cross-section of disciplines, making firm recommendations to reduce the unacceptable premature mortality and disease burden from avoidable causes and to improve the standard of care for patients with liver disease in hospital. From the substantial number of recommendations given in our Commission, we selected those that will have the greatest effect and that need urgent implementation. Although the recommendations are based mostly on data from England, they have wider application to the UK as a whole, and are in accord with the present strategy for health-care policy by the Scottish Health Boards, the Health Department of Wales, and the Department of Health and Social Services in Northern Ireland.

Enhanced liver fibrosis test can predict clinical outcomes in patients with chronic liver disease

Background Clinicians use fibrosis in a liver biopsy to predict clinical outcomes of chronic liver disease. The performance of non-invasive tests has been evaluated against histological assessment of fibrosis but use of clinical outcomes as the reference standard would be ideal. The enhanced liver fibrosis (ELF) test was derived and validated in a large cohort of patients and shown to have high diagnostic accuracy (area under the curve (AUC)=0.80 95% CI 0.76 to 0.85) in identification of significant fibrosis on biopsy. Objective To evaluate ELF performance in predicting clinical outcomes by following up the original ELF cohort. Methods Patients recruited to the ELF study at seven English centres were followed up for liver morbidity and mortality by examination of clinical data. Defaulting/discharged patients were followed up by family practitioner questionnaires. Primary outcome measure was liver-related morbidity/liver-related death. Results 457 patients were followed up (median 7 years), with ascertainment of clinical status in 92%. There were 61 liver-related outcomes (39 deaths). Survival analysis showed that the ELF score predicts liver outcomes, with people having the highest ELF scores being significantly more likely to have clinical outcomes than those in lower-score groups. A Cox proportional hazards model showed fully adjusted HRs of 75 (ELF score 12.52–16.67), 20 (10.426–12.51) and 5 (8.34–10.425) compared with patients with ELF <8.34. A unit change in ELF is associated with a doubling of risk of liver-related outcome. Conclusions An ELF test can predict clinical outcomes in patients with chronic liver disease and may be a useful prognostic tool in clinical practice.

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.

Cyclosporin a treatment in primary biliary cirrhosis: Results of a long-term placebo controlled trial

BACKGROUND Effective treatment for primary biliary cirrhosis (PBC) resulting in slower progression and improved survival remains elusive. Cyclosporin A (CyA), which has been so effective in preventing human allograft rejection, has shown promise in small numbers of patients in early studies. METHODS Three hundred forty-nine patients with PBC were randomized to receive CyA, 3 mg.kg-1.day-1, or placebo in a multicenter study with follow-up for 6 years. The end point was death or liver transplantation. RESULTS Cox multivariate analysis showed time from entry to death or transplantation was significantly prolonged (by up to 50%) in the CyA-treated group. Liver-related mortality was also significantly lower. However, a univariate analysis of survival showed no statistical differences between the two groups. Biochemical liver indices deteriorated more slowly in the CyA-treated group, but serum creatinine concentration was elevated > 150 mumol/L in 9%, necessitating permanent discontinuation in half of these. A reduction in the dose of CyA was required in 11% because of hypertension. CONCLUSIONS CyA has some therapeutic potential in primary biliary cirrhosis, providing blood pressure and renal function are closely monitored.

LIVER DISEASE AND BILEDUCT ABNORMALITIES IN ADULTS WITH CYSTIC FIBROSIS

A quarter of adults with cystic fibrosis, 57 of 233, had abnormal liver function. Patients with hepatic dysfunction were further investigated by ultrasound, hepatobiliary scintigraphy, and endoscopic retrograde cholangiography (ERC). 17 of the 23 patients studied had abnormalities on imaging. All 15 patients who underwent ERC had abnormal intrahepatic ducts, but only 2 had stricture of the common bile duct. These findings suggest that, in patients with cystic fibrosis, intrahepatic impairment of biliary drainage may be important in the pathogenesis of liver disease.

Pancreatic Pseudocyst in Chronic Pancreatitis: Endoscopic and Surgical Treatment

SurgeryIntroductionThe incidence and prevalence of chronic pancreatitisappear to be increasing [1–4]. Pancreatic pseudocyst is acommon complication of chronic as well as acute pancre-atitis that is unrelated to the underlying aetiology. Ad-vances in radiological techniques have in part led to anincrease in the diagnosis of pseudocyst and better charac-terization of associated complications. There is now a bet-ter understanding of the natural history of pseudocysts inrelation to the underlying disease. The introduction ofnew treatment modalities has also increased the optionsfor surgical management. Thus with better knowledge ofthe disease and with technical advances the indications,timing and methods to treat pancreatic pseudocysts haveundergone a marked evolutionary change.DefinitionA pancreatic pseudocyst is a localised collection ofpancreatic-enzyme-rich fluid, originating in or adjacent tothe pancreas and enclosed in a wall of granulation and/orfibrous tissue lacking an epithelial lining [5]. The princi-ple mechanism leading to pseudocyst formation is be-lieved to involve disruption of the main pancreatic ductand/or peripheral ductules causing leakage and activationof pancreatic enzymes, which in turn leads to localisedautodigestion and necrosis of pancreatic parenchyma.This evokes an inflammatory response with the formationof a distinct pseudocyst wall composed of granulation tis-sue and blood vessels that organizes with more connectivetissue and fibrosis [6–11].On-table pancreatography [12] and endoscopic retro-grade cholangiopancreatography (ERCP) have demon-strated a communication between the pseudocyst and thepancreatic ductal system in up to 80% of the patients [13,14], and peripheral or main pancreatic duct disruption isknown to be an early event in acute pancreatitis [15].Rarely disruption of a retention cyst [16] or trauma thatdisrupts the pancreatic ductal system may also lead to apseudocyst [17–19].

Randomised study of endoscopic biliary endoprosthesis versus duct clearance for bileduct stones in high-risk patients

BACKGROUND The value of an endoprosthesis for long-term management of bileduct stones has not been formally established. The main theoretical advantage of endoprosthesis insertion (BE) over conventional endoscopic duct clearance (DC) is the prevention of stone impaction, with obstruction and consequent cholangitis or pancreatitis. In a randomised study we compared the results of these two methods in patients with symptomatic bileduct stones who were at high risk because of old age (> 70 yr) or serious debilitating disease. METHODS 43 high-risk patients were randomised to BE with a 7F double-pigtail endoprosthesis and < 0.75 cm sphincterotomy, and 43 to DC with standard 1.25-1.50 cm sphincterotomy and stone extraction by balloon or basket, with or without mechanical lithotripsy. The principal endpoint was the rate of biliary related complications. FINDINGS In the BE group biliary drainage was achieved in the first session in all but one patient (who required 2 sessions). In the DC group, 24 patients had duct clearance at the first attempt and 35 (81%) after a median of 2 sessions (range 2-4); eight of this group had an endoprosthesis inserted to maintain long-term drainage. At 72 h the complication rates were 7% in the BE group and 16% in the DC group (p = 0.18). However, the long-term complication rate for BE was higher: by Kaplan-Meier analysis, at a median of 20 months the proportions free of biliary complications were 64% BE and 86% DC (p = 0.03, log-rank test). INTERPRETATION For immediate bileduct drainage, endoprosthesis insertion proved a safe and effective alternative to duct clearance. Because of the risk of subsequent cholangitis, its use as a definitive treatment should be confined to highly selected cases.

Regulation of intestinal non-haem iron absorption

Iron is a precious metal in biological terms, having essential roles in oxygen transport, electron transfer and as a cofactor in many enzyme systems, including DNA synthesis. The biological importance of iron is underscored by the evolution of very complex mechanisms for its acquisition, utilisation and preservation in even the most primitive organisms. These systems have evolved because bioavailability of iron is limited and also because its biological activity is potentially toxic as seen, for example, in haemochromatosis. In humans, iron loss from the body is minimall and the level of iron is controlled by regulating its absorption from the intestine.2 3Iron in food is available in two forns haem iron (in muscle as myoglobin and haemoglobin) and non-haem iron (in vegetables, cereals and meat). Haem iron accounts for only 10-20% of dietary iron in industrialised countries but can contribute a disproportionate 30% ofthe absorbed iron due to its higher bioavailability. Non-haem iron accounts for 80% of dietary iron in industrialised countries and an even greater proportion worldwide or in vegetarians.4 For this reason it is more important from a worldwide perspective and it is also more affected by other micronutrients and by regulatory mechanisms in the intestine.5 Non-haem iron absorption can be considered to occur in two phases-first, the assimilation of iron from the intestinal lumen into the epithelial cell and, second, the transfer or export of the assimilated iron to plasma. Both of these phases are known to be responsive to the level of body iron stores,6 but the intracellular mechanisms influencing these phases and the mechanism by which the enterocyte is informed of body iron requirements are poorly understood. Here, we draw together evidence from older physiological experiments and more recent studies using cell and molecular biology techniques to speculate how this recent information may be pertinent to how iron is taken up by enterocytes, how its transfer to plasma is controlled and, finally, how information about body iron stores or requirement is conveyed to enterocytes and by what mechanism this information can influence both of these

Hereditary pancreatic endocrine tumours

The two main types of hereditary pancreatic neuroendocrine tumours are found in multiple endocrine neoplasia type 1 (MEN-1) and von Hippel-Lindau disease (VHL), but also in the rarer disorders of neurofibromatosis type 1 and tuberous sclerosis. This review considers the major advances that have been made in genetic diagnosis, tumour localization, medical and surgical treatment and palliation with systemic chemotherapy and radionuclides. With the exception of the insulinoma syndrome, all of the various hormone excess syndromes of MEN-1 can be treated medically. The role of surgery however remains controversial ranging from no intervention (except enucleation for insulinoma), intervening for tumours diagnosed only by biochemical criteria, intervening in those tumours only detected radiologically (1–2 cm in diameter) or intervening only if the tumour diameter is >3 cm in diameter. The extent of surgery is also controversial, although radical lymphadenectomy is generally recommended. Pancreatic tumours associated with VHL are usually non-functioning and tumours of at least 2 cm in diameter should be resected. Practice guidelines recommend that screening in patients with MEN-1 should commence at the age of 5 years for insulinoma and at the age of 20 years for other pancreatic neuroendocrine tumours and variously at 10–20 years of age for pancreatic tumours in patients with VHL. The evidence is increasing that the life span of patients may be significantly improved with surgical intervention, mandating the widespread use of tumour surveillance and multidisciplinary team management.