D. C. Carter

The effect of polyunsaturated fatty acids on the progress of cachexia in patients with pancreatic cancer.

Cachexia is common in patients with pancreatic cancer and has been associated with persistent activation of the hepatic acute phase response and increased energy expenditure. Fatty acids have been shown to have anticachectic effects in animal models and to reduce inflammatory mediators in healthy subjects and patients with chronic inflammatory disease. Eighteen patients with unresectable pancreatic cancer received dietary supplementation orally with fish oil capsules (1 g each) containing eicosapentaenoic acid 18% and docosahexaenoic acid 12%. Anthropometric measurement, body composition analysis, and measurement of resting energy expenditure and serum C-reactive protein were performed before and after supplementation with a median of 12 g/day of fish oil. Patients had a median weight loss of 2.9 kg/month (IQR 2-4.6) prior to supplementation. At a median of 3 months after commencement of fish oil supplementation, patients had a median weight gain of 0.3 kg/month (IQR 0-0.5) (p < 0.002). Changes in weight were accompanied by a temporary but significant reduction in acute phase protein production (p < 0.002) and by stabilisation of resting energy expenditure. This study suggests a component fish oil, perhaps EPA, merits further investigation in the treatment of cancer cachexia.

Factors influencing morbidity and mortality in acute pancreatitis; an analysis of 279 cases.

Of 279 patients admitted to a specialist unit with acute pancreatitis, 210 were admitted directly and 69 were transferred for treatment of local or systemic complications. Outcome was assessed in terms of mortality and morbidity and in relation to aetiology, predicted severity of disease (modified Glasgow score), organ failure (modified Goris multiple organ failure score), and need for surgical intervention. The death rate was 1.9% in patients admitted directly but was 18.8% in those transferred from other units. Mortality in gall stone related pancreatitis was 3% compared with 15% (p = 0.03) in pancreatitis of unknown aetiology and 27% (p = 0.01) in post-endoscopic retrograde cholangiopancreatography pancreatitis. Mortality was related to age (mortality > 55 years old 11% v 2%; p = 0.003) and Goris score (score 0, mortality 0% v score 5-9, mortality 67%; p = 0.001). In patients transferred from other units, mortality was 11% in those transferred within a week of diagnosis and 35% when transfer was delayed (p = 0.04). Thirty six patients had pancreatic necrosis on dynamic computed tomography of whom 29 underwent pancreatic necrosectomy with a 34% mortality. Mortality was related to the modified Goris score (median score 2 in survivors v 6 in non-survivors; p = 0.005) and was higher when necrosectomy was performed within the first two weeks of admission (100% vs 21%; p = 0.004). In conclusion, mortality in acute pancreatitis is influenced by age, aetiology of the disease, and presence of organ failure. Patients transferred for specialist care have a 10-fold greater mortality than those admitted directly and mortality is greatest when transfer is delayed. Early necrosectomy carries a prohibitively high mortality.

Glutamine-supplemented total parenteral nutrition reduces blood mononuclear cell interleukin-8 release in severe acute pancreatitis

Glutamine, a conditionally essential amino acid, is important for immune function. It is now being formulated for incorporation into total parenteral nutrition (TPN). The aims of this study were to examine the effect of glutamine administration on lymphocyte proliferation and proinflammatory cytokine release in patients with severe acute pancreatitis. Fourteen patients were randomized (in a double-blind fashion) to receive either conventional or isocaloric, isonitrogenous glutamine-supplemented (0.22 g glutamine x kg(-1) x d(-1) as glycyl-glutamine) TPN for 7 d. DNA synthesis (index of lymphocyte proliferation) and the 24-h release of tumor necrosis factor (TNF), interleukin (IL)-6, and IL-8 from peripheral blood mononuclear cells were measured in vitro on days 0, 4, and 7. Thirteen patients completed the study protocol (6 glutamine TPN, 7 conventional TPN). Glutamine supplementation increased median DNA synthesis by 3099 cpm over the study period against 219 cpm in the conventional group (increase not significantly different between the two groups) . Glutamine supplementation did not significantly influence TNF or IL-6 release, but, in contrast, median IL-8 release was reduced by day 7 in the glutamine group while it was increased in the conventional group (-17.7 ng/mL (median change over study period) versus +43.3 ng/mL, respectively; P=0.045). Small patient numbers and substantial interindividual variation limit the conclusions, but there is a trend for the glutamine group to have improved lymphocyte proliferation, and in the case of IL-8, reduced proinflammatory cytokine release.

Endoscopic retrograde cholangiopancreatography and acute pancreatitis

Endoscopic retrograde cholangiopancreatography (ERCP) is firmly established as a valuable method for the diagnosis and treatment of biliary and pancreatic disease, and has a particularly important role in acute pancreatitis, when gall stones are suspected. Neoptolemos and colleagues randomised patients thought to have gall stone pancreatitis to receive conservative management or urgent ERCP with sphincterotomy if stones were present in the bile duct. In patients with predicted mild disease on Glasgow criteria, urgent ERCP conferred no benefit, whereas it was associated with significantly lower morbidity in patients with predicted severe pancreatitis. None of the patients with mild disease in this trial died. There were fewer deaths in patients with severe disease who received urgent ERCP, although the difference was not statistically significant. A serum bilirubin concentration in excess of 40 ,umomll proved a strong indicator of persisting bile duct stones and the need for ERCP.1 2 In a similar study from Hong Kong, early ERCP with sphincterotomy if stones were found reduced the incidence of biliary sepsis but did not affect mortality or the incidence of local and systemic complications.3 In patients with acute pancreatitis of uncertain origin, ERCP may prove invaluable once the acute episode has settled to determine whether gall stones are present.4 The potential importance of biliary sludge as a cause of acute pancreatitis has also been highlighted recently. Of 31 patients with idiopathic pancreatitis in one series, 23 (740/o) had microscopic evidence of sludge (that is, calcium bilirubinate crystals or cholesterol monohydrate crystals) in duodenal aspirates. Pancreatitis recurred in only one of 10 patients undergoing cholecystectomy or endoscopic papillotomy compared with eight of 11 patients having no such treatment.5 Early ERCP is probably unnecessary in patients with mild pancreatitis and should be avoided during the acute episode in patients without gall stones. Although the available results of early endoscopic intervention in patients with predicted severe gall stone pancreatitis are encouraging, some believe that the severity of an episode (and the risk of necrosis) is determined early, and that the amount of activated enzyme is more important than persisting impaction of a gall stone at the ampulla of Vater.6 If there is a window of opportunity during which an episode of pancreatitis can be aborted by endoscopic sphincterotomy and stone extraction this window may be short-lived and have passed even before some patients reach hospital. Experimental necrotising pancreatitis in the opossum caused by obstructing the biliopancreatic duct system by a balloon catheter is less severe if the catheter is removed at one or three days compared with five days,7 lending support to the concept that early endoscopic removal of obstructing stones is beneficial in gall stone pancreatitis. Despite its potential benefits, ERCP is not without risk in that it can actually cause acute pancreatitis, and result in significant morbidity and even mortality. Clinical acute pancreatitis occurs in some 1-5% of patients undergoing ERCP8 9 while asymptomatic hyperamylasaemia may be present in up to 50% of patients. In a referral centre treating 279 patients with acute pancreatitis over a five year period, ERCP was the causal factor in 4% of cases.10 While the overall death rate in the 279 patients in our review was 6%, three of 11 patients in the subgroup with ERCP related pancreatitis died, a death rate of 27%. Multiple or high pressure injections of contrast into the pancreatic duct, is a well recognised risk factor for ERCP related pancreatitis particularly when acinar filling of the pancreas is seen.11 Other risk factors include therapeutic endoscopic intervention, a past history of pancreatitis, and operator inexperience. The indication for ERCP may also be important and pancreatitis in one report was commoner when sphincter of Oddi dysfunction was being evaluated than when ERCP was being performed because of other indications, particularly gall stones.12 Of the four patients who died in a series of 14 patients developing acute pancreatitis after ERCP, all showed a rising serum bilirubin concentration in the first 48 hours after the procedure. There was no such rise in those who survived. The lethal combination of ERCP related pancreatitis and subsequent deterioration in liver function could not be accounted for by the explanatory variables of age, sex, presence of choledocholithiasis at the time of ERCP, successful duct clearance, inadvertent production of a pancreatogram or the pre-ERCP serum bilirubin concentration when examined in a logistic regression model. The number of patients in this analysis is small so that the significance of a rising serum bilirubin after ERCP