Raised hepatic free fatty acids in a patient with acute fatty liver after gastric surgery for morbid obesity.

A patient died after gastric surgery for morbid obesity. Necropsy showed severe fatty liver, and biochemical analysis of hepatic lipids showed unusually high free fatty acid concentrations, which may have contributed to the hepatic failure.

Biochemical and histological assessment of hepatic lipid in sudden infant death syndrome.

A biochemical and histological study of hepatic lipid in children dying from the sudden infant death syndrome (SIDS) and children of a similar age dying explicably are reported. Contrary to a previous report based on histological assessment of hepatic lipid, no significant increase of total lipid content in livers of children dying from SIDS was found. Analysis of hepatic phospholipid fatty acid esters, however, revealed a significant difference between SIDS and children of similar age dying acutely and explicably. The phospholipid abnormality found in SIDS was similar to that found in children dying subacutely with hypoxia and would be consistent with increased cell membrane fluidity. The implications of these findings in the pathogenesis of SIDS are discussed.

Chronic alcoholic skeletal muscle myopathy: a clinical, histological and biochemical assessment of muscle lipid.

Muscle biopsy samples were analysed from five control subjects, four patients with mild to moderate fibre atrophy and four patients with severe atrophy. Patchy increase in lipid was noted with oil red O staining but there was no consistent association of lipid with selective fibre types. Ultrastructural studies demonstrated lipid droplets both subjacent to the sarcolemma and between fibrils. Quantitative analysis showed that the increased lipid was solely due to excess triglyceride. GLC analysis of free and esterified acids was performed. The profiles were essentially similar for the phospholipid and free fatty acid fractions. The triglyceride fraction showed a decrease of myristate, stearate and linoleate with an increase in oleate and arachidate in the alcoholic tissue compared with control. The cholesteryl ester fraction showed an increase in palmitate with a decrease in stearate and oleate in the alcoholic muscle. The accumulation of lipid correlated with mean daily alcohol consumption but not with degree of atrophy suggesting that the two processes probably had different pathogenic mechanisms.

Micromethods for quantitative lipid analysis of human liver needle biopsy specimens.

Micromethods are described for rapid quantitative lipid analysis of human liver specimens obtained by percutaneous needle biopsy. Total phospholipid, free fatty acids, triacylglycerol and free and esterified cholesterol were separated by thin layer chromatography and, with the aid of an internal standard, quantitated by specific chemical assays. Individual phospholipids were also separated and quantitated. Fatty acid esters were transmethylated and assayed by gas-liquid chromatography. The results of recovery and reproducibility experiments and lipid values for normal human liver are reported. These methods provide a new approach for investigating the pathogenesis of liver disease and may well prove useful in analysing lipids from biopsies of other tissues.

A prospective series of out-patient endoscopic retrograde cholangiopancreatography.

OBJECTIVE: Out-patient endoscopic retrograde cholangiopancreatography (ERCP) is widely practised but the safety of this approach has only been addressed in a limited number of prospective series mainly from specialist North American centres. Our objective was to determine prospectively the safety and admission rates of out-patient ERCPs. STUDY DESIGN AND PARTICIPANTS: Patients were selected for out-patient ERCP if in relatively good health, without major risk factors for complications following ERCP and with adequate social support. Our series consisted of 136 consecutive cases of which 82 were therapeutic. SETTING AND OUTCOME MEASURES: A district general hospital in the UK, which also performs ERCPs for neighbouring health districts. Out-patient ERCP patients were followed up at 30 days using standard criteria for defining complications. RESULTS: Procedures were 60 biliary sphincterotomy, 10 stone removal, nine stenting procedures, two dilatations and one pancreatic intervention. Complications were pancreatitis in seven patients (six moderate severity, one mild), cholangitis in three patients, haemorrhage in one patient. Nine patients required admission for complications, two from the endoscopy unit and seven from home; their average in-patient stay was 6 days. Seventeen patients were admitted for observation or for further management. There was one death unrelated to ERCP. Overall, 110 of 136 patients did not require inpatient care following out-patient ERCP. CONCLUSIONS: Our complication rates were similar to those of other series. Out-patient ERCP for selected cases, with adequate post-discharge arrangements for advice and readmission, appears safe and would reduce healthcare costs.

Analysis and subcellular localization of lipid in alcoholic liver disease.

The nature and subcellular distribution of lipids in alcoholic liver disease have been little studied. Micro-methods for lipid analysis were applied to needle biopsy homogenates and their subcellular fractions. Alcoholic fatty liver was accompanied by a major increase (up to 50 fold) in triglyceride and a smaller (2-3 fold) increase in cholesteryl ester: there was no significant change in the free cholesterol, free fatty acid or phospholipid content. Homogenates were fractionated into macro- and micro-droplets and membrane fractions by differential centrifugation. The subcellular location of the membrane lipids were determined by sucrose density gradient centrifugation in a vertical pocket reorientating rotor. In fatty liver, although there was a 2-3 fold increase in macro-droplet and micro-droplet (tentatively identified as VLDL) lipid, the major increase was in the membrane-bound triglyceride (8-10 fold). Sucrose density gradient centrifugation demonstrated that these membranes had an equilibrium density of 1.12 g/ml, clearly separated from droplet lipid, density less than 1.04 g/ml. The membrane fraction was tentatively identified as Golgi in origin and it is suggested that alcoholic fatty liver in man is due to impaired Golgi secretion of triglyceride-rich lipid complexes.

Role of endoscopic endoprostheses in proximal malignant biliary obstruction.

The management of hilar strictures is dependent upon their resectability and may therefore require a multidisciplinary approach. However, resectability rates for such tumors are reported to be in the region of 15%-20%, and, therefore, palliative therapy will be the mainstay of treatment for most patients. With the presenting symptoms being those of obstructive jaundice and the consequences of cholestasis, a significant improvement in morbidity can be obtained by achieving biliary drainage. A number of options are available, including the placement of Teflon or expandable metallic endoprostheses by either the endoscopic or percutaneous route. Some considerable debate exists as to which route of stent placement is best, and in many circumstances the decision will depend on the availability of local services. Some have suggested that success rates with percutaneous stenting are superior to those for endoscopic placement, but the latter technique may be associated with fewer complications. In competent hands, endoscopic placement does achieve a high rate of success and it should be remembered that a combined approach may further improve success rates. The debate over the use of plastic versus metallic stents is centered around the higher rates of stent occlusion/migration for plastic stents seen in some studies, although a stent change is usually possible. An additional advantage of metallic stents is that they may provide drainage of the side branches of the biliary tree through the mesh. However, possible drawbacks may be a greater difficulty in placement of a second stent where a first provides inadequate drainage, and cost issues often have to be taken into consideration. Considerable debate exists over the optimum number of stents required to achieve adequate drainage and minimize the risks of cholangitis. There is good evidence that if overfilling of the biliary tree with contrast is avoided with only the segments to be drained visualized, a single stent may be all that is required, while others argue that placement of more than one stent may improve survival. In the following review we discuss these issues, and conclude by considering success rates and complications following endoprosthesis insertion; we also discuss the prognosis of patients treated in this way.

Biochemical analysis of hepatic lipid in alcoholic and diabetic and control subjects.

Percutaneous needle biopsy specimens of liver were obtained from alcoholic, diabetic and control patients. Micro-methods of lipid separation and quantification were employed to determine the detailed nature of hepatic lipid. Triglyceride is the major accumulating liver lipid in both alcoholic and diabetic patients. Cholesteryl ester levels were raised in both alcoholic and diabetic patients but only diabetic patients had significantly increased free cholesterol and phospholipid levels. Determination of phospholipid/free cholesterol ratios revealed a significant decrease in alcoholic cirrhosis compared with controls. Fatty acid ester analysis of hepatic phospholipid and triglyceride revealed significant differences between alcoholic patients and controls but not between diabetic patients and controls. An increased ratio of non-essential/essential fatty acids was found in the patients with alcoholic liver disease whereas those of diabetic patients were similar to the controls.

Isolation of micro- and macro-droplet fractions from needle biopsy specimens of human liver and determination of the subcellular distribution of the accumulating liver lipids in alcoholic fatty liver.

Needle biopsy specimens of liver were obtained from six control subjects with histologically normal liver and 11 chronic alcoholics with fatty liver. Micro- and macro-lipid droplet fractions were isolated by differential flotation. These fractions, together with the sedimenting membranes, were assayed for cholesterol, cholesteryl ester, phospholipid, free fatty acids and triglyceride. Electron microscopy demonstrated marked differences in the range of lipid droplet sizes in the two fractions and biochemical analysis suggested that the microdroplet lipid corresponded to pre-very low density lipoprotein (VLDL) particles. Studies on biopsies from patients with alcoholic fatty liver showed a 2-3-fold increase in triglyceride in both lipid droplet fractions but most of the accumulating triglyceride was sedimentable and membrane-bound. Needle biopsy specimens from two patients with alcoholic fatty liver were fractionated with a vertical pocket re-orientating rotor. The principal organelles were separated and the subcellular distribution of triglyceride, phospholipid and free cholesterol determined. Triglyceride showed a bimodal distribution to a particulate fraction tentatively located to Golgi particles and to droplet-lipid remaining in the sample layer.

Activities and subcellular distributions of hepatic lipases in control subjects and in patients with alcoholic fatty liver.

Human hepatic lipase activities were studied in needle biopsy specimens by fluorogenic and radioisotopic assay methods. Using analytical subcellular fractionation by sucrose density gradient centrifugation a lysosomal acid lipase, with pH optimum of 4.0, and an endoplasmic reticulum alkaline lipase, with pH optimum of 8.5, were demonstrated with the fluorogenic assay. The apparent Km of the acid lipase was 17 mumol/l by the fluorogenic method and 23 mmol/l by the radioisotopic method. The values for alkaline lipase were 94 mumol/l and 1.4 mmol/l respectively. Assay of these activities in biopsies from 16 control subjects and 42 chronic alcoholics showed increasing activity with increasing hepatic fatty infiltration when the fluorogenic assay was used: no differences were demonstrated with radioisotopic assay. These results suggest that depressed lipolysis due to a relative deficiency of triglyceride lipase is not a causal factor in triglyceride accumulation in chronic alcoholic fatty liver.

Biliary surgery without the surgeon!

Since the introduction of endoscopic retrograde cholangiopancreatography in the 1970s and of endoscopic sphincterotomy (EST) in 1974, endoscopic techniques for the diagnosis and therapy of biliary and pancreatic disorders have proliferated. Although some procedures have become part of routine practice, for example EST for postcholecystectomy bile duct stones and stent insertion for inoperable biliary strictures, the place of others is unclear at present and should be evaluated by prospective randomized clinical trials. The choice of either an endoscopic or a transhepatic approach for biliary disease is usually dictated by local expertise, but these should be regarded as complementary rather than competing techniques, and complex biliary problems should be managed jointly by the endoscopist, interventional radiologist and hepatobiliary surgeon.

Additional endoscopic procedures instead of urgent surgery for retained common bile duct stones.

One hundred and twenty seven patients were treated by nasobiliary drainage, or stenting, to prevent biliary obstruction after endoscopic failure to clear stones from the common bile duct. At presentation, 91 (72%) patients were jaundiced and 39 (31%) had cholangitis. Placement of either a nasobiliary drain or stent was successful in 124 (98%) patients. One hundred and twenty one (95%) patients were followed up. Clearance was ultimately achieved endoscopically in 52 and surgically in 25 patients after (mean) 2.4 months. Thirty day mortality was 3%. There were no complications of nasobiliary drainage, but two of 39 patients treated by temporary stents developed cholangitis, both successfully managed by endoscopic duct clearance. Forty two patients unfit for surgery or further endoscopic attempts at duct clearance were followed with stents in situ for a mean 15.9 months (range 2.5-37.5). Cholangitis developed in four patients and was successfully managed by stent change. These results indicate that longterm stenting can be useful for poor risk surgical patients and that nasobiliary drainage or temporary stenting permits further elective rather than urgent endoscopic or surgical treatment.

Endoscopic management of choledocholithiasis during pregnancy.

Extrahepatic biliary obstruction by gallstones during pregnancy is a difficult management problem. We present five patients--four with acute cholangitis and one with gallstone pancreatitis--in whom a surgical procedure was avoided by endoscopic sphincterotomy. All five women delivered healthy babies at term. Endoscopic retrograde cholangiopancreatography and sphincterotomy can be performed safely in pregnancy with minimal exposure to radiation. Endoscopic management should be considered in women presenting with acute cholangitis or gallstone pancreatitis during pregnancy.

A 10 year single centre experience of percutaneous and endoscopic extraction of bile duct stones with T tube in situ.

A non-randomised single centre study of 226 consecutive patients referred over 10 years with retained common bile duct stones and a T tube in situ or a cholecystostomy tube are reported. Percutaneous extraction was attempted in 204 and endoscopic extraction in 68 patients. Percutaneous clearance was achieved in 158 (77.5%) patients and endoscopic clearance in 52 (76.5%) patients. Six of 153 (3.9%) patients followed after percutaneous treatment suffered major complications (pancreatitis, cholangitis, or tract perforation). Three of 67 (44%) patients followed after endoscopic treatment suffered major complications (pancreatitis, cholangitis, or bleeding). When the initial method of treatment failed, the alternative was used, resulting in an overall success rate of bile duct clearance of 94.3%. It is concluded that percutaneous and endoscopic methods of bile duct clearance in patients with a T tube in situ are equally effective, carrying similar complication rates. This study has helped to clarify the indications and efficacy of these alternative treatments.

Sclerosing cholangitis in acquired immunodeficiency syndrome. Case reports and review of the literature.

Four patients with acquired immunodeficiency syndrome (AIDS) (CDC group IV) were investigated for biliary disease because of the presence of both severe upper abdominal pain and raised levels of serum alkaline phosphatase. None was clinically jaundiced. Upper abdominal ultrasound was abnormal in three. All had endoscopic retrograde cholangiographic evidence of both an intrahepatic sclerosing cholangitis suggestive of primary sclerosing cholangitis and an irregular suprapapillary common bile duct dilation suggestive of papillary stenosis. Three had evidence of gastrointestinal cryptosporidiosis and two of disseminated cytomegalovirus infection. Endoscopic sphincterotomy, performed in two patients, gave good pain relief. We propose the name 'AIDS sclerosing cholangitis' for this form of secondary cholangitis. The cause of this disorder remains unclear. Recent evidence is discussed which suggests that it is not due to HIV itself but to an opportunistic infection. Cryptosporidium appears to be the most likely candidate.