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Background: The liver is a source of systemic proinflammatory mediators in acute pancreatitis. We have investigated the effects of blood from the pancreas and intestine in liver activation and lung inflammation during early stages of experimental acute pancreatitis in a rat model., Methods: A portosystemic shunt and a mesosystemic shunt were created to prevent the passage of blood coming from the pancreas and the intestine, respectively, to the liver. Pancreatitis was induced by retrograde injection of 5% sodium taurocholate into the biliopancreatic duct. After 3 hours, the inflammatory process in the lung and intestine, plasma levels of tumor necrosis factor (TNF)-alpha and their soluble receptor, and mRNA expression of inflammatory mediators in the lung were evaluated., Results: Portocaval shunting of blood prevented the inflammatory process in the lung, an increase in plasma TNF-alpha concentration, and the expression of TNF-alpha, interleukin (IL)-1beta, and heat-shock protein (HSP)-72 in the lung, but had no effect on plasma levels of soluble TNF-alpha receptor or on expression of inducible nitric oxide synthase (iNOS) and macrophage inflammatory protein (MIP)-2 in the lung. In contrast, mesocaval shunting of blood did not modify any of the parameters evaluated., Conclusions: Pancreatic blood, but not intestinal blood, plays a key role in liver activation during experimental acute pancreatitis.

Background and Objective: Although hypertriglyceridemia is an accepted cause of acute pancreatitis, its clinical course is not well defined. What is more, lipemic serum may interfere with an accurate pancreatic enzyme measurement and may hinder the diagnosis of acute pancreatitis. The objective was to analyze the clinical performance of hypertriglyceridemic acute pancreatitis and the diagnosis value of the serum measurement of pancreatic enzymes., Patients and Method: 31 demographic, clinical, analytical and radiological data of 19 hypertriglyceridemic acute pancreatitis were retrospectively analyzed and their results were compared with data of 19 lithiasic acute pancreatitis without hypertriglyceridemia. Diagnosis of acute pancreatitis was based on clinical, radiological and/or laparotomical findings. Serum levels of triglycerides higher than 1,000 mg/dl were considered the cause of acute pancreatitis when other causes were excluded. Acute pancreatitis was considered lithiasic when gallstones were identified by ultrasonography, serum levels of triglycerides were lower than 200 mg/dl and there was no history of alcohol consumption., Results: Compared with lithiasic acute pancreatitis, hypertriglyceridemic acute pancreatitis showed more personal and family hypertriglyceridemia (9 vs 0), more previous episodes of pancreatitis (13 vs 2), pancreatitis was more severe (13 vs 5) and had more complications (29 vs 5). There was no mortality in either group. The serum levels of amylase and lipase supported the diagnosis in 26% and 58% of patients with hypertriglyceridemic acute pancreatitis compared with 58% and 79% of patients with lithiasic acute pancreatitis, respectively. Hospital stay was longer in hypertriglyceridemic than in lithiasic acute pancreatitis (24 [45] vs 7.6 [3.1] days; p = NS). Demographic and analytical factors which could permit to predict the severity of acute pancreatitis could not be identified., Conclusions: Hypertriglyceridemic acute pancreatitis is relapsing and its clinical course is more severe than lithiasic acute pancreatitis. The measurement of amylase and lipase levels is less useful in the diagnosis of hypertriglyceridemic than in lithiasic acute pancreatitis.

Background: In recent years, technological advances and technical refinements to laparoscopic instruments have encouraged some surgeons to explore the application of laparoscopic methods to benign disorders of the pancreas. The aim of this report was to evaluate the feasibility and outcome of laparoscopic pancreatic surgery in patients with chronic pancreatitis., Methods: One group of five patients with disease of nonalcoholic origin localized in the body-tail of the pancreas underwent distal pancreatectomy with preservation of the splenic vessels; a second group of six patients with symptomatic pancreatic pseudocysts (alcoholic origin in four cases and idiopathic in two cases) underwent laparoscopic transgastric drainage. For distal pancreatectomy and spleen salvage, the patient's positioning was half-lateral decubitus with the left side up. Four ports were used. A comparison was made with 41 patients with chronic, pancreatitis who underwent conventional open distal pancreatectomy. For the patients with laparoscopic distal pancreatectomy, the mean operative time was 4 h (range 3-5)., Results: There were no pancreatic-related complications, but one patient was reoperated for perforation of duodenal ulcer. The mean hospital stay was 6 days and the mean time to resume normal daily activities was 3 weeks. Laparoscopic pseudocyst drainage was performed in four patients via laparoscopic anterior gastrostomy and two patients via laparoscopic intraluminal cystogastrostomy. The mean operative time was 100 min (range 60-160). There was no morbidity. The mean hospital stay was 5 days, and the mean time to resume normal daily activities was 2 weeks., Conclusion: This study provides information about the possibilities of performing laparoscopic surgery in patients with chronic pancreatitis. Laparoscopic distal pancreatectomy with preservation of the splenic vessels and laparoscopic transgastric drainage are feasible and safe techniques. They offer obvious advantages, such as reduction of the parietal damage to the abdomen, a shorter hospital stay, and an earlier postoperative recovery than can be obtained with conventional open pancreatic resection.

Objective: To investigate the role of P-selectin and intercellular adhesion molecule-1 (ICAM-1) in the pathogenesis of lung injury associated with pancreatitis, and the relation between xanthine oxidase-derived oxidants and expression of these adhesion molecules., Summary Background Data: In acute pancreatitis, acute respiratory distress syndrome occurs in the early stages of disease. This process is mediated by neutrophil infiltration., Methods: Pancreatitis was induced in rats by intraductal administration of 5% sodium taurocholate. ICAM-1 and P-selectin expression was measured using radiolabeled monoclonal antibodies. Neutrophil infiltration and plasma levels of xanthine oxidase were also evaluated., Results: Pancreatitis induces increases in P-selectin expression in lung, whereas ICAM-1 is unchanged from baseline levels. Immunoneutralization of either P-selectin or ICAM-1 prevents the infiltration of neutrophils into the lung. Xanthine and xanthine oxidase activity were increased after induction of pancreatitis. Xanthine oxidase inhibition prevents the upregulation of P-selectin in lung and neutrophil infiltration., Conclusions: During acute pancreatitis, P-selectin is upregulated in the pulmonary endothelium and is a key determinant of leukocyte recruitment. Constitutive ICAM-1 is also involved in the process of cell infiltration into the lung. The increased expression of P-selectin appears to be triggered by a mechanism dependent on free radicals generated by xanthine oxidase released by the damaged pancreas.

Objective: To evaluate (1) whether alveolar macrophages are activated as a consequence of acute pancreatitis (AP), (2) the implication of inflammatory factors released by these macrophages in the process of neutrophil migration into the lungs observed in lung injury induced by AP, and (3) the role of the liver in the activation of alveolar macrophages., Summary Background Data: Acute lung injury is the extrapancreatic complication most frequently associated with death and complications in severe AP. Neutrophil infiltration into the lungs seems to be related to the release of systemic and local mediators. The liver and alveolar macrophages are sources of mediators that have been suggested to participate in the lung damage associated with AP., Methods: Pancreatitis was induced in rats by intraductal administration of 5% sodium taurocholate. The inflammatory process in the lung and the activation of alveolar macrophages were investigated in animals with and without portocaval shunting 3 hours after AP induction. Alveolar macrophages were obtained by bronchoalveolar lavage. The generation of nitric oxide, leukotriene B4, tumor necrosis factor-alpha, and MIP-2 by alveolar macrophages and the chemotactic activity of supernatants of cultured macrophages were evaluated., Results: Pancreatitis was associated with increased infiltration of neutrophils into the lungs 3 hours after induction. This effect was prevented by the portocaval shunt. Alveolar macrophages obtained after induction of pancreatitis generated increased levels of nitric oxide, tumor necrosis factor-alpha, and MIP-2, but not leukotriene B4. In addition, supernatants of these macrophages exhibited a chemotactic activity for neutrophils when instilled into the lungs of unmanipulated animals. All these effects were abolished when portocaval shunting was carried out before induction of pancreatitis., Conclusion: Lung damage induced by experimental AP is associated with alveolar macrophage activation. The liver mediates the alveolar macrophage activation in this experimental model.

The purpose of this paper is to present the results of our experience in using a conservative pancreatic resection approach in a certain group of patients suffering from chronic pancreatitis. From January 1988 to December 1995, 110 patients underwent surgical therapy for chronic pancreatitis at the Hospital Clinic of the University of Barcelona. In 35 patients with an inflammatory mass at the pancreatic head, pylorus-preserving duodeno-pancreatectomy was performed. Forty male patients with localized focal pancreatitis at the body or tail underwent distal pancreatectomy and drainage of the pancreatic remnant. In 30 patients with pancreatic ducts greater than 7 mm in diameter, side-to-side pancreaticojejunostomy was carried out. Five patients could not be included in any of these three categories because of their particular characteristics. In all cases, resolution of the symptoms was achieved at the mean follow-up of 18 months (range 12 to 21 months). No patient showed a deterioration of glucose homeostasis, and exocrine dysfunction was not observed. Patients with obstructive chronic pancreatitis by inflammatory cystic mass, short strictures or intraductal stones located in the central pancreas or uncinate process may be surgically managed with conservative pancreatic resection or extraction of the stones from the Wirsung duct. The jejunal interposition and pancreaticojejunal anastomosis achieved pain control without any deterioration of the endocrine or exocrine function.

Functional and morphologic changes that take place in the pancreatic gland after an episode of acute pancreatitis have been the subject of discussion among experts in recent years. At the present time there are enough studies to support the fact that for a certain time if not permanently after acute pancreatitis a variable number of patients continue to show morphologic pancreatic changes in the pancreas and exocrine functional impairment. These changes are clearly seen to be related to the severity and alcoholic etiology of the pancreatitis. There are also indications of possible progression from acute alcoholic pancreatitis to chronic pancreatitis, related to severity and recurrence. It is more probable that it is the first instance of pancreatitis in a pancreas that has previously suffered asymptomatic alcohol-induced impairment. The vascular and gastrointestinal tract complications that make a late appearance after acute pancreatitis, although infrequent, on occasion confronts the patient with a high risk of mortality, especially in cases of perforation and hemorrhage.

The role of nitric oxide in lipoxygenase metabolism after a process of ischemia-reperfusion in pancreas transplantation has been evaluated in this study. Sprague-Dawley rats were randomized into three groups, as follows: Group I--Control animals not surgically manipulated; Group II.--Pancreas transplantation, after 12 h of organ preservation; Group III.--Same as II but with administration of NG-nitro-L-arginine methyl esther (a nitric oxide synthase inhibitor) (10 mg/Kg) prior to organ revascularization. The results show post-transplantation increases in leukotriene B4 and 12-hydroxyeicosatraenoic acid levels in pancreatic tissue. Nitric oxide synthase inhibition reversed the increases in 12-hydroxyeicosatetraenoic acid, but was unable to modify leukotriene B4 increases suggesting the existence of a direct effect of nitric oxide on the 12-lipoxygenase metabolism in pancreas transplantation.

The role of liver in the respiratory dysfunction associated with acute pancreatitis has been evaluated. For this purpose, an experimental necrohemorrhagic pancreatitis was induced in rats by intraductal administration of 3.5% sodium taurocholate. Additionally, a portocaval shunt was performed before induction of acute pancreatitis to prevent the initial passage through the liver of substances released by the pancreas. Twelve hours after the induction of pancreatitis, increases in lung prostacyclin and thromboxane B2 synthesis, decreased lung superoxide dismutase activity, and increases in plasma phospholipase A2 activity were found. In addition, inflammatory injury was evidenced in lung by histopathological analysis. The portocaval shunt was able to prevent the metabolic changes and ameliorate the inflammatory process in the lung, suggesting that the liver plays an active role in the systemic inflammatory response to acute pancreatitis.

The role of nitric oxide in eicosanoid and oxygen-free radical production in the early stages of sodium taurocholate-induced acute necrotizing pancreatitis has been studied. Male Wistar rats were divided into three groups: group I: control group, a volume of 0.1 ml/100 g body wt saline solution was injected at low pressure in the pancreatic duct; group II: acute pancreatitis was induced by administration of 3.5% sodium taurocholate; and group III: intravenous administration of NG-nitro-L-arginine methyl esther (a nitric oxide synthase inhibitor) 5 min before induction of acute pancreatitis as stated for group II. At 5 and 60 min after induction of pancreatitis, blood and pancreas tissue samples were taken for assays. Increases in 6-keto PGF1 alpha, TXB2, PGE2, PGF2 alpha, and 12-HETE were observed in the pancreatic tissue. Lipoperoxidation was also enhanced and remained unaltered after nitric oxide inhibition. The fact that nitric oxide synthase inhibition could only reverse the increases in 6-keto PGF1 alpha and TXB2 levels indicates that in acute pancreatitis endothelial and platelet eicosanoid generation is mediated through an nitric oxide-dependent mechanism. In contrast, nitric oxide appears to be not related with oxygen free radical damage associated with acute pancreatitis.

Oxygen free radicals (OFR) are postulated to play a role in the pathogenesis of acute pancreatitis. The aim of this work was to examine the role of xanthine oxidase in the generation of OFR and the activity of the endogenous defense mechanisms as reflected by pancreatic superoxide dismutase (SOD) activity in a model of edematous pancreatitis induced in rats by administration of cerulein at supramaximal doses, as well as in necrohemorrhagic model induced by intraductal administration of sodium taurocholate. Comparison between these two models of pancreatitis suggests important differences in origin and importance in the evolution of injury. In necrohemorrhagic pancreatitis OFR can be produced by xanthine oxidase activity probably associated to cell death. By contrast, in cerulein induced pancreatitis, other sources of oxygen free radicals, such as inflammatory cells, can be of more importance.

A multicenter study of acute necrotizing pancreatitis (ANP) classified in accordance with the Balthazar criteria (grades D and E), has been performed in 12 teaching hospitals. A total of 233 patients were reviewed, and the mortality rate was 26.6%. The most common etiology was biliary pancreatitis (45.5%). Among the complications, shock, renal insufficiency, pulmonary insufficiency and hemorrhagic gastritis were associated with a mortality rate of 51-66%. Diffuse fluid collections were associated with a higher mortality rate (26.8%) than localized fluid collections (14.5%). In 106 patients with gallstone pancreatitis, early surgery was performed in 17, and 5 patients (29.4%) died. No mortality was observed in 32 patients with delayed surgery. Sphincterotomy was performed in 13 patients, and 4 (30.7%) died. Early surgery (necrosectomy and closed peritoneal lavage) was undertaken in 75 patients, with a mortality rate of 39%. In conclusion, the morbidity and mortality rates of ANP can be improved with proper monitoring, adequate supportive care and the judicious use of surgery based on clinical and morphological findings.

Changes in endogenous pancreas production of prostaglandins D2, F2 alpha, E2, and E1 in early stages of acute necrotizing pancreatitis induced by intraductal administration of 3.5% sodium taurocholate have been determined by radioimmunoassay of chromatographically purified tissue extracts. For this purpose 18 male Wistar rats were randomized in three groups: control, pancreatitis, and pancreatitis plus indomethacin. Pancreas tissue samples were obtained 5 min after pancreatitis induction. In the pancreatitis-induced group, prostaglandins D2, F2 alpha, and E2 show significantly increased tissue levels relative to the controls whereas prostaglandin E1 remains unmodified. These results suggest a role for series 2 prostaglandins in the earlier stages of pancreatitis.

Ten patients who had undergone whole-organ pancreas transplantation and pancreatoduodenocystostomy from a total of 60 simultaneous cadaveric kidney-pancreas transplants met the criteria for graft pancreatitis. This condition is clearly different from acute rejection on the basis of marked hyperamylasaemia and significant local findings over the allograft. Graft rejection was the cause of graft loss in one of the patients; eight are alive, seven with a functioning graft 61, 30, 27, 25, 21, 18 and 14 months after transplantation. Two patients died: one from severe graft pancreatitis and the other from cytomegalovirus infection. Bladder drainage with or without antibiotics has been the most common therapy, based on the theory that damage is caused by duodenal content and infected urine reflux. To prevent graft loss, antiviral treatment should be given when pancreatitis due to cytomegalovirus is suspected or diagnosed. Two patients with native pancreatitis are also described; the disease was severe and surgery was required in both cases. The pancreas grafts have now been functioning for 2 years 7 months and 2 years 10 months respectively.

Pancreatic ascites is the accumulation of high protein, amylase-rich intraperitoneal fluid which occurs during the course of chronic pancreatitis, in association with rupture of a pseudocyst or disruption of a pancreatic duct. This is an uncommon complication, with less than 250 cases reported in the literature. We have treated 6 patients with pancreatic ascites. Five were males with a history of chronic alcoholism, but no known pancreatic disease. The diagnosis was made by ascitic tap and the site of the leakage identified by ERCP. Treatment was initiated with total parenteral nutrition in all cases. In 5 patients, the ascites failed to respond to medical therapy. Surgical intervention was indicted in 3 of these patients. The diagnosis of pancreatic ascites should be considered in patients with refractory ascites, and a combination of medical care and judicious surgery have contributed to an improved outcome.

Prostacyclin metabolism in rat acute pancreatitis was evaluated by measuring the tissue levels of 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) and the urinary excretion of 2, 3-dinor 6-keto-PGF1 alpha. Acute pancreatitis was induced by i.v. cerulein perfusion and was confirmed by the pancreas enzyme changes and the histological findings. Significantly enhanced tissue and urinary prostacyclin levels were found in acute pancreatitis rats, when compared to the controls. Concomitantly, an enhanced tissue phospholipase A2 (PLA2) activity was also found. These data show the importance of 2, 3-dinor PGF1 alpha as an inflammatory marker in cerulein-induced pancreatitis.

Post-transplantation pancreatitis is an infrequent complication with a high risk of mortality. In a 7-year period, there were five patients who had documented pancreatitis out of a total of 488 renal homograft recipients, an incidence of 1 per cent. Two cases occurred in patients with an orthotopic transplant, one of them as a result of surgical injury of the pancreas and the other as a consequence of cytomegalovirus infection. The third case was an acute pancreatitis of hypercalcaemic origin, the fourth patient developed postoperative pancreatitis and acute acalculous cholecystitis, and the fifth had acute pancreatitis and sepsis associated with cytomegalovirus infection. Three patients died as a direct result of the complication. The mean incidence and mean mortality rate of post-transplantation pancreatitis, as determined from our review of the literature of the last 15 years, are 2.3 and 61.3 per cent, respectively; these are similar to the figures found up to 1970 of 1.7 and 52.2 per cent. A multiplicity of factors present in the uraemic patient may be responsible for the continued frequency of post-transplant pancreatitis despite advances in surgical technique and immunosuppressive therapy.