Simmy Bank

Cytokines (IL-6, IL-8, TNF): early and reliable predictors of severe acute pancreatitis.

Background Severe acute pancreatitis is associated with a high mortality, especially when compared with mild acute pancreatitis. Early intervention in patients with severe acute pancreatitis has been shown to improve mortality. The value of cytokines (interleukin [IL]-6, IL-8 and tumor necrosis factor [TNF]-alpha) in diagnosing severe acute pancreatitis at an early stage was studied. Study Thirty-six patients with acute pancreatitis were prospectively evaluated. Age-matched controls were obtained from healthy volunteers. Levels of IL-6, IL-8, and TNF-alpha were obtained within 24 hours of admission. Ransons prognostic signs and Banks clinical criteria were used to differentiate patients into mild and severe pancreatitis. Results There was significant difference in IL-6 levels between controls and mild pancreatitis, controls and severe pancreatitis, and mild and severe pancreatitis. IL-8 levels were significantly different between controls and severe pancreatitis and mild and severe pancreatitis. There was no significant difference between controls and mild pancreatitis. The results for TNF-alpha were similar to the findings for IL-8. Conclusion IL-6, IL-8, and TNF can be used independently in differentiating mild acute pancreatitis from early severe acute pancreatitis.

The influence of cigarette smoking on cytokine levels in patients with inflammatory bowel disease

Anecdotal reports suggest that smoking may be beneficial for patients with inflammatory bowel disease (IBD) as nicotine may act through inflammatory mediators within the colonic mucosa. Furthermore, there is increasing evidence that cytokines play a pathologic role in IBD. Our aim was to determine the effects of cigarette smoking on cytokine levels in the colonic mucosa of patients with and without IBD. Mucosal biopsies were obtained from 10 patients with Crohns disease (CD), 10 with ulcerative colitis (UC), and 10 healthy controls. Five of 10 patients in each of the three groups were smokers and five were nonsmokers. Concentrations of interleukin (IL)-1beta, IL-2, IL-6, and IL-8 were determined using enzyme-linked immunosorbent assay (ELISA). Cytokine levels of smokers were compared with nonsmokers in each group and with controls. Results were analyzed using the Mann-Whitney test; significance was set at p<0.05. The concentration of IL-8 was significantly higher in healthy controls who smoke compared with nonsmokers and significantly reduced in smokers with CD compared with nonsmokers with CD. Moreover, concentrations of IL-1beta and IL-8 were significantly reduced in smokers with UC compared with nonsmokers with UC. Smokers had significantly elevated levels of IL-8 in the colonic mucosa. Smokers with IBD had a significant reduction in cytokine levels; specifically, IL-1beta and IL-8 for patients with UC and IL-8 for patients with CD. Further studies are warranted to determine if this reduction in cytokine levels is histologically and clinically significant.

CAUSES OF ACUTE AND RECURRENT PANCREATITIS: Clinical Considerations and Clues to Diagnosis

The causes of acute pancreatitis are well documented and usually are divided into alcohol-induced, gallstone, miscellaneous, and idiopathic when no immediate cause is found. Clinically, the cause is either immediately discernable from the history and a few standard investigations, less obvious and requiring more detailed studies, or obscure and even speculative. The physician can whittle away at the idiopathic group by increasingly recognizing causes such as biliary sludge or microlithiasis, sphincter of Oddi dysfunction, hereditary pancreatitis, cystic fibrosis, or autoimmune causes. The prevalence of these and other rare conditions is the focus of intense research. Whether these increasingly recognized causes will significantly alter the current incidence of 10% to 30% of cases classified as idiopathic pancreatitis, only time will tell.

Combined ligation and sclerotherapy versus ligation alone for secondary prophylaxis of esophageal variceal bleeding: a meta-analysis.

OBJECTIVES:Variceal ligation has been shown to be superior to sclerotherapy in prevention of rebleeding and improving survival in patients with cirrhosis. However, 25% of patients will rebleed before completion of treatment. A number of trials have compared the combination of ligation and sclerotherapy to ligation alone in achieving rapid and complete eradication of esophageal varices, with conflicting results.METHODS:Two reviewers independently identified seven randomized, controlled trials that compared endoscopic variceal ligation with the combination of sclerotherapy and ligation for the treatment of esophageal varices. Studies were identified by searching MEDLINE, reviewing references from retrieved articles, and scanning abstracts from conference proceedings. For each outcome, odds ratios (ORs) were calculated using fixed-effects and random-effects models. The Mantel-Haenszel test for statistical heterogeneity was used to assess the validity of combining results from individual studies.RESULTS:No significant difference was seen in cessation of actively bleeding varices (OR = 1.01, 95% CI = 0.43–2.36), variceal rebleeding (OR = 1.12, CI = 0.69–1.81), and mortality (OR = 1.1, CI = 0.70–1.74) in patients with variceal ligation versus patients receiving the combination treatment of ligation and sclerotherapy. Treatment sessions required to achieve complete variceal eradication were similar in the two treatment arms. A significantly higher incidence of esophageal stricture was seen in combination therapy (p < 0.001).CONCLUSIONS:The combination of ligation and sclerotherapy offers no advantage over ligation alone in prevention of rebleeding and in reduction of mortality. It is also associated with a higher complication rate of esophageal stricture.

Mucosal cytokine production in radiation-induced proctosigmoiditis compared with inflammatory bowel disease

OBJECTIVE:We measured the mucosal levels of interleukin 1β (IL-1β), IL-2, IL-6, and IL-8 in affected segments of radiation-induced proctosigmoiditis and compared these with the levels in normal controls and inflammatory bowel disease (IBD) patients.METHODS:Thirteen patients with histologically proven radiation proctosigmoiditis, 32 patients with active ulcerative colitis (UC), 35 patients with Crohns disease, and 15 normal subjects undergoing routine colonoscopy were included in the study. All patients underwent colonoscopy and mucosal biopsies were obtained from both diseased and normal-appearing areas. Mucosal levels of IL-1β, IL-2, IL-6, and IL-8 were determined by solid-phase enzyme-linked immunosorbent assay (ELISA) using the Quantikine method (R&D Systems, Minneapolis, MN). All the data were statistically analyzed using Students t test.RESULTS:The mucosal levels of IL-2, IL-6, and IL-8 were significantly higher in both diseased segments (5.62 ± 0.13, 1.60 ± 0.31, and 21.45 ± 4.03 pg/ml, respectively) and normal-appearing segments (3.83 ± 0.78, 1.36± 0.34, and 13.45 ± 3.18 pg/mg) in the radiation proctitis group compared to those of normal control subjects (1.74 ± 0.23, 0.67 ± 0.09, and 4.99 ± 1.39 pg/mg). These differences were statistically significant. (p < 0.05). In the UC group, IL-1β, IL-6, and IL-8 levels in diseased segments were 4.98 ± 0.53, 2.22 ± 0.28, and 88.85 ± 8.05 pg/mg, respectively. In Crohns disease patients, IL-1β, IL-6, and IL-8 levels were 5.45 ± 0.93, 2.88 ± 0.58, and 61.68 ± 10.02 pg/mg, respectively. All these levels were significantly higher (p < 0.05) compared with IL-1β, IL-6, and IL-8 levels from normal segments of IBD patients. Compared with the radiation proctitis patients, the levels of IL-6 and IL-8 were significantly higher in the IBD group.CONCLUSIONS:The mucosal levels of IL-2, IL-6, and IL-8 were significantly higher in both diseased and normal segments of colon in patients with radiation proctitis, compared with normal controls. Only IL-1β levels were significantly higher in diseased segments, compared with endoscopically normal-appearing segments in radiation proctitis. These results indicate that there is a similarity in the activation of mucosal cytokines between IBD and radiation proctosigmoiditis. This may partly explain the beneficial effects of similar topical and systemic agents such as steroids and mesalamine compounds when used in radiation-induced proctosigmoiditis.

Infected pancreatic necrosis and peripancreatic fluid collections: Serendipitous response to antibiotics and medical therapy in three patients

Three patients with clinical and radiologic evidence of pancreatic necrosis or peripancreatic fluid collections/inflammatory masses who were advised to have surgery on the basis of bacterial infection on skinnyneedle aspiration of the pancreas but were deemed medically unstable or refused operative intervention were treated with intensive antibiotic therapy. All three patients survived the attack of acute pancreatitis with infection on medical therapy alone. This suggests that occasional patients with infected necrosis and/or peripancreatic collections/inflammatory masses may respond to antibiotics, especially those antibiotics that have recently been shown to have a high penetration into pancreatic tissue.

Antacid versus sucralfate in preventing acute gastrointestinal bleeding. A randomized trial in 100 critically ill patients.

A randomized, controlled trial of sucralfate versus antacid as prophylaxis against upper gastrointestinal bleeding was carried out in 100 critically ill intensive care unit patients. Both groups were comparable with regard to sex, age, duration of prophylaxis, and the number of risk factors per patient. There was no gross bleeding in any of the patients. Three of the 48 sucralfate patients and 2 of the 52 antacid patients showed strongly positive results of Gastroccult tests of three successive hourly samples of gastric aspirate and were considered treatment failures. We conclude that sucralfate therapy is as effective as an antacid regimen in the prevention of gastrointestinal bleeding in critically ill patients. In view of a considerable savings in nursing time, it offers the opportunity for considerable reduction in the cost of intensive care while providing effective protection.

Analysis of risk factors predictive of early mortality and urgent ERCP in acute cholangitis.

Background Multifactor prognostic scoring systems have been developed for acute pancreatitis to identify those patients with a potentially poor prognosis. A similar system for patients with acute cholangitis is still lacking. Goals To identify common clinical, biochemical, and etiologic variables that can be used to predict mortality and the need for early endoscopic retrograde cholangiopancreatography (ERCP) in patients with acute cholangitis. Study A retrospective study of 108 patients with acute cholangitis was performed at a single center. Univariate analysis and logistic regression were used to identify variables that were significantly associated and predictive of mortality and need for early ERCP. Results Univariate analysis identified 18 variables significantly associated with mortality and 15 variables that predicted the need for early ERCP. Through logistic regression total bilirubin (P<0.01), partial prothrombin time (P<0.01), and presence of a liver abscess (P<0.01) were found to be significant in predicting mortality. Alanine aminotransferase (P<0.01) and white blood cell count (P<0.01) were determined to be predictive of a need for early ERCP. The scoring systems for predicting mortality (93.9%, 80.7%) and early ERCP (98%, 91%) were both highly sensitive and specific, respectively. Conclusions Acute cholangitis is a disease that presents with varying severity. We report a scoring system that can be used to identify patients at high risk of early mortality and those that may benefit from earlier ERCP.

Hyperamylasemia in Inflammatory Bowel Disease

We determined the prevalance and significance of hyperamylasemia in 180 patients with idiopathic inflammatory bowel disease (IBD) (83 with ulcerative colitis, and 97 with Crohns disease). Serum total amylase and pancreatic and salivary isoamylase activity were measured in all patients. In all patients with hyperamylasemia, we measured isoamylase activity by cellulose acetate electrophoresis and lipase activity, assayed for the presence of macroamylase, and carried out pancreatic ultrasound examination and barium studies of the upper gastrointestinal tract. Eight of 97 patients with Crohns disease (8%) had hyperamylasemia; 4 of them had an elevated pancreatic isoamylase and 2 a raised lipase activity. All patients with hyperamylasemia had normal ultrasonographic scans of the pancreas and no evidence of duodenal involvement on barium meal. None had macroamylasemia. We found no relationship of hyperamylasemia to disease site, activity, and duration or therapy and no patient developed clinical evidence of pancreatitis. We conclude that a small but important number of patients with Crohns disease have hyperamylasemia not associated with overt pancreatitis. In the absence of appropriate indications, it requires no investigation.

Pylephlebitis—diagnosis and management

1. Dusheiko G. Side effects of alpha interferon in chronic hepatitis C. Hepatology 1997;26(suppl 1):112S–21S. 2. Mellstedt H, Osterborg A, Bjorkholm M, et al. Induction treatment witha-interferon in multiple myeloma: An interim report from MGCS. Eur J Haematol 1989;43:124–8. 3. Marcellin P, Pouteau M, Martinot-Peignoux M, et al. Lack of benefit of escalating dosage of interferon alpha in patients with chronic hepatitis C. Gastroenterology 1995;109:156–65. 4. Jett GK. Captopril-induced angioedema. Ann Emerg Med 1984;13:489–90. 5. Israili ZH, Hall WD. Cough and angioneurotic edema associated with angiotensin-converting enzyme inhibitor therapy. A review of the literature and pathophysiology. Ann Intern Med 1992;117:234–42. 6. Messerli FH, Nussberger J. Vasopeptidase inhibition and angio-oedema. Lancet 2000;356:608–9. 7. Naldi L, Ferri C, Locati T, et al. Cutaneous reactions to analgesic-antipyretics and nonsteroidal anti-inflammatory drugs. Dermatology 1993;186:164–9. 8. Chin HL, Buchan DA. Severe angioedema after long-term use of an angiotensin-converting enzyme inhibitor. Ann Intern Med 1990;112:312–3. 9. Shionoiri H, Takasaki I, Hirawa N, et al. A case report of angioedema during long-term (66 months) angiotensin converting enzyme inhibition therapy with enalapril. Jpn Circ J 1996;60:166–70. 10. Schiller PI, Messmer SL, Haefeli WE, et al. Angiotensinconverting enzyme inhibitor-induced angioedema: Late onset irregular course, and potential role of triggers. Allergy 1997; 52:432–5. 11. Anderson MW, deShazo RD. Studies of the mechanism of angiotensin-converting enzyme (ACE) inhibitor-associated angioedema: The effect of an ACE inhibitor on cutaneous responses to bradykinin, codeine, and histamine. J Allergy Clin Immunol 1990;85:856–8. 12. Nussberger J, Cugno M, Amstutz C, et al. Plasma bradykinin in angio-oedema. Lancet 1998;351:1693–7. 13. Blais C Jr, Rouleau JL, Brown NJ, et al. Serum metabolism of bradykinin and des-Arg9-bradykinin in patients with angiotensin-converting enzyme inhibitor-associated angioedema. Immunopharmacology 1999;43:293–302. Reprint requests and correspondence:Kenji Ohmoto, M.D., Division of Gastroenterology, Department of Medicine, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama 701-0192, Japan. Received Nov. 28, 2000; accepted Dec. 6, 2000.