Hepatic dysfunction is a frequent complication of total parenteral nutrition (TPN), indicated by derangement of standard liver function tests. However, such changes are variable and nonspecific, and represent hepatic injury rather than changes in hepatic function. Antipyrine (Phenazone) clearance is a sensitive indicator of hepatic microsomal enzyme activity and provides a more specific indication of hepatic function. This was used to investigate the effect of different TPN regimens. Patients receiving a postoperative 2000 kcal TPN regimen providing all nonprotein calories as dextrose (n = 16) showed a 34% reduction of mean antipyrine clearance after 7 days of TPN compared to controls (n = 13, p less than 0.05). This effect was seen also in patients receiving a 1600 kcal dextrose-based regimen (n = 8). In patients receiving a 2000 kcal TPN regimen in which 500 kcal were provided as lipid (n = 10), mean antipyrine clearance was not significantly different from that of the control group. This study indicates the sensitivity of hepatic microsomal oxidative function, an important route of drug metabolism, to different TPN regimens.

Patients presenting with adenocarcinoma of the vermiform appendix at the Royal Preston and Chorley District General Hospitals were reviewed for the 15 year period 1972-1986. Eleven cases were identified, representing a rate of 1 in 956 for all appendicectomies performed. A third of the cases presented as acute appendicitis. However, of 8 patients who initially had an appendicectomy, only 4 subsequently underwent further surgery (right hemicolectomy). One patient died of recurrent disease. Five of the patients presenting were under 60 years of age. During the same period, the total number of appendicectomies performed annually declined by 50%. The study highlights the need to subject all appendicectomy specimens to histological examination, and that the disease presents in a younger age group than commonly seen for malignant colonic neoplasms.

Cholecystitis caused by Campylobacter is rare with only 14 cases found in the literature. This case describes a 71-year-old man who presented with right hypochondrial abdominal pain due to a gangrenous gallbladder identified at laparotomy. Culture of a bile sample identified a slow-growing gram-negative bacterium identified as Campylobacter jejuni. After a poor clinical response, this identification allowed targeted antibiotic treatment resulting in a slow but successful recovery and discharge 17 days postoperatively. This case demonstrates the importance of considering rare organisms in severe acute cholecystitis and ensuring appropriate cultures are performed, particularly in those who fail to respond to initial antimicrobial treatment.

Summary: An experimental model, originally designed to study the effects of controlled interruption of the enterohepatic circulation (EHC), has been extensively modified and adapted to study the applied physiology of an “intact” EHC of bile in Rhesus monkeys. Basically, the model consists of a surgically exteriorised extrahepatic biliary circuit in which an electronic stream splitter is interposed. This diverts every twentieth drop of bile which provides a representative sample for analysis while returning the remaining 95% of bile to the upper intestine. During these studies, the monkeys were comfortably restrained in specially designed chairs whose construction is described in detail. Animal maintenance and the design of the electronic stream splitter are also described. Analysis of the glycine: taurine and the dihydroxy: trihydroxy bile salt ratios both in gallbladder bile and in bile obtained with an “intact” EHC (by using the stream splitter), showed that the Rhesus monkey secretes a bile similar in composition to that of man. The bile salt: cholesterol: phospholipid ratios in monkey gallbladder bile (81:6:13) were also similar to those found in human bile, indicating that this animal is suitable for studies of cholesterol solubility in bile – a factor of major importance in gallstone pathogenesis. The model has been used to measure bile volume, bile salt secretion, pool size and the frequency of circulation of the bile salt pool. The diurnal variation in these variables has also been studied.

Patients presenting with adenocarcinoma of the gallbladder within Newcastle upon Tyne over a 5 year period (1980-1985) were reviewed retrospectively. The mean age of patients on diagnosis was 74 years. Of the 29 patients diagnosed, two were detected after routine cholecystectomy. Laparotomy was performed in 21 patients (72%) of which only 14 patients had a cholecystectomy performed. Mean survival after surgery was 6.6 months with only one patient alive after 5 years. Metastatic disease was present in 72% of patients. The poor prognosis of carcinoma of the gallbladder reflects its late diagnosis and early metastasis to distant sites. Improvement in survival will depend upon early detection of in situ lesions and identification of at risk patients.

This study examines the effect of parenteral nutrition on hepatic triglyceride secretion in postoperative patients. Five patients received fluids and electrolytes only (D/S), 10 received a 2000-kcal total parenteral nutrition (TPN) formula with 25% of the nonprotein energy from lipid (LIPID-TPN), and 11 received a similar regimen with all of this energy from dextrose (CHO-TPN). After 7 days an intravenous bolus of 3H-glycerol was given and hepatic triglyceride secretion measured from the decay curve of plasma radiolabeled triglyceride content. Plasma triglyceride concentrations were similar in each group. Hepatic triglyceride secretion was 16.3 mg/kg/hr after D/S, 10.7 mg/kg/hr after LIPID-TPN, and 12.2 mg/kg/hr after CHO-TPN (NS). There was no correlation between the rate of hepatic secretion and dextrose intake. Both TPN regimens resulted in significant reductions in plasma concentrations of apoproteins A1 and B but this did not appear to be related to triglyceride secretion rates. Despite the similar rates of hepatic secretion the quantity of labeled glycerol secreted in triglyceride was significantly greater after CHO-TPN (17629 dpm/24 hr) than either D/S (10560 dpm/24 hr) or LIPID-TPN (7264 dpm/24 hr, p less than 0.05), indicating that recycling of exogenous lipid may have occurred after LIPID-TPN. This study indicates that hepatic triglyceride secretion is not suppressed by TPN, irrespective of the energy source, but suggests that the rate of secretion may have an upper limit.

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I read with interest the recent paper by Nakagawa et all concerning the development of hepatic steatosis in the parenterally fed rat. However, I dispute the authors' conclusions that steatosis is prevented or reduced by the presence of essential fatty acids in the total parenteral nutrition (TPN) regimens used. The degree of hepatic steatosis observed was more likely related to the carbohydrate content of the TPN, which provided 85%, 77%, and 60% of the total calories in the three study groups.The sensitivity of hepatic function to carbohydratederived calories has been known for some time.' In humans, hepatic steatosis occurs because of lipogenesis from TPN-derived carbohydrate, exceeding a fixed rate of hepatic triglyceride secretion as very low density lipoprotein.' Accumulation of lipid disrupts hepatocytes and results in the clinically observed derangement in liver function. In contrast, the pathogenesis of steatosis in the rat is due to a reduction of hepatic triglyceride secretion and is independent of the effect of essential fatty acid deficiency.4 4 Inclusion of lipid calories during TPN results in reduction of lipogenesis and maintenance of liver function.Specifically, hepatic microsomal enzyme function (P45o enzyme activity), impaired by dextrose-based TPN regimens, appears to be protected by the provision of exogenous lipid emulsion.' The pathogenesis of hepatic steatosis during TPN is therefore dextrose related and species specific. In addition, nutritional bypass of the gastrointestinal tract may increase the susceptibility of the liver to the development of steatosis secondary to depletion of gut-derived serum apolipoproteins. REFERENCES 1. Nakagawa M, Hiramatsu Y, Mitsuyoshi K, et al: Effect of various lipid emulsions on total parenteral nutrition-induced hepatosteatosis in rats. JPEN 15:137-143, 1991 2. Lamson PD, Greig ME, Hobdy CJ: Modification of barbiturate anaesthesia by glucose, intermediary metabolites and certain other substances. J Pharmacol Exp Ther 103:460-470, 1951 3. Burgess P, Johnston IDA, Hall RI: Effect of different energy sources on hepatic triglyceride secretion during parenteral nutrition. JPEN 12:569-573, 1988 4. Hall RI, Grant JP, Ross LH, et al: The pathogenesis of hepatic steatosis in the parenterally fed rat. J Clin Invest 74:1658-1668, 1984 5. Burgess P, Hall RI, Bateman DN, et al: The effect of total parenteral nutrition on hepatic drug oxidation. point is well taken. The mechanism of the development of steatosis, especially with respect to secretion of triglyceride during total parenteral nutrition (TPN), is problematic. Unfortunately, we did not experiment to ascertain the answer to the question he has raised regarding exceeding a fixed rate of hepatic triglyceride secretion or a reduction of hepatic triglyceride secretion. Actually, we found a difference in hepatic lipid content during glucose TPN and during lipid TPN. Furthermore, we noted different hepatic lipid contents among various lipid TPN groups. During TPN, under the same conditions, differences in the fatty ...