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Background /Objectives: Evaluation of the local and systemic effects of aging on the severity of acute pancreatitis (AP) in an experimental rat model in elderly animals. Methods AP was induced in Wistar rats by intraductal 2.5% taurocholate injection and divided into two groups: Young (3 month old) and Aged (18 month old). Two and 24 h after AP induction blood samples were collected for determinations of amylase, AST, ALT, urea, creatinine, glucose, and of plasma I-FABP. TNF-α and IL-6 levels were determined in serum and ascitic fluid. Liver mitochondrial function and malondialdehyde (MDA) contents, pancreas histological analysis, and pulmonar myeloperoxidade (MPO) activity were performed. Bacterial translocation was evaluated by bacterial cultures of pancreas. Results A significant increase in serum amylase, AST, ALT, urea, creatinine, glucose, I-FABP, and IL-6 levels, and a reduction in serum and ascitic fluid TNF-α levels were observed in the aged group compared to the young group. Liver mitochondrial dysfunction, MDA contents, and pulmonary MPO activity were increased in the Aged AP group compared to the Young AP group. Positive bacterial cultures obtained from pancreas tissue in aged group were significantly increased compared to the young group. Acinar necrosis was also increased in aged AP group when compared to young AP group. Conclusion Aging worsens the course of acute pancreatitis evidenced by increased local and systemic lesions and increased bacterial translocation.

OBJECTIVE: To evaluate the prognostic significance of microvessel density and p53 expression in pancreatic cancer. METHODS: Between 2008 and 2012, 49 patients with pancreatic adenocarcinoma underwent resection with curative intention. The resected specimens were immunohistochemically stained with anti-p53 and anti-CD34 antibodies. Microvessel density was assessed by counting vessels within ten areas of each tumoral section a highpower microscope. RESULTS: The microvessel density ranged from 21.2 to 54.2 vessels/mm2. Positive nuclear staining for p53 was found in 20 patients (40.6%). The overall median survival rate after resection was 24.1 months and there were no differences in survival rates related to microvessel density or p53 positivity. Microvessel density was associated with tumor diameter greater than 3.0 cm and with R0 resection failure. CONCLUSIONS: Microvessel density was associated with R1 resection and with larger tumors. p53 expression was not correlated with intratumoral microvessel density in pancreatic adenocarcinoma.

Background: Intracellular calcium overload is known to be a precipitating factor of pancreatic cell injury in acute pancreatitis (AP). Intracellular calcium homeostasis depends of Plasmatic Membrane Calcium ATPase (PMCA), Sarcoplasmic Endothelial Reticulum Calcium ATPase 2 (SERCA 2) and the Sodium Calcium Exchanger (NCX1). The antioxidant melatonin (Mel) and Trisulfate Disaccharide (TD) that accelerates NCX1 action could reduce the cell damage determined by the AP. Aim: To evaluate m-RNA expressions of SERCA2 and NCX1 in acute pancreatitis induced by sodium taurocholate in Wistar rats pre-treated with melatonin and/or TD. Methods: Wistar rats were divided in groups: 1) without AP; 2) AP without pre-treatment; 3) AP and Melatonin; 4) AP and TD; 5) AP and Melatonin associated to TD. Pancreatic tissue samples were collected for detection of SERCA2 and NCX1 m-R NA levels by polymerase chain reaction (PCR). Results: Increased m-RNA expression of SERCA2 in the melatonin treated group, without increase of m-RNA expression of the NCX1. The TD did not affect levels of SERCA2 and NCX1 m-RNA expressions. The combined melatonin and TD treatment reduced the m-RNA expression of SERCA2. Conclusions: The effect of melatonin is restricted to increased m-RNA expression of SERCA2. Although TD does not affect gene expression, its action in accelerating calcium exchanger function can explain the slightest expression of SERCA2 m-RNA when associated with Melatonin, perhaps by a joint action of drugs with different and but possibly complementary mechanisms.

Background Identification of molecular markers in pancreatic adenocarcinoma (PA) has the potential to guide targeted therapy. The objective of this study is to determine the prognostic significance of epidermal growth factor receptor (EGFR) expression (membrane and cytoplasmic) in resected PA and its correlation with lymph node metastasis and survival. Methods EGFR overexpression was determined by immunohistochemistry, and the pattern of expression was compared between the primary tumour, adjacent normal pancreas and involved lymph nodes. Results A total of 88 patients had curative resection. No difference was found in mEGFR overexpression between tumoural and metastatic nodal tissues (P = 0.28). Median overall survival time was 22.9 months. Overall cumulative 1-, 3- and 5-year survival was 48%, 20% and 18%, respectively. In positive mEGFR tumour expression, survival was 46% at 1 year, 8% at 3 years and 0% at 5 years (P < 0.05). Univariate analysis showed that male gender, portal vein (PV) resection, perineural, lymphovascular and peri-pancreatic invasion, positive margins and positive mEGFR expression in tumour tissue had worse survival. Multivariate analysis showed that male gender, PV resection, vascular and perineural invasion remained independent predictors of poor survival. Conclusion Positive mEGFR overexpression is associated with decreased survival; however, it is not an independent prognostic factor.

Colloid resuscitation in acute pancreatitis (AP) is a matter of controversy due to the possible deleterious effect on lung function. A previous study demonstrates that albumin administration increases lung damage in burns and this effect can be reversed by inducible nitric oxide synthase (iNOS) inhibition. This study evaluates the effects of S-methylisothiourea (SMT), a specific iNOS inhibitor, on lungs and pancreas of rats with AP receiving intravenous albumin.AP was induced in Wistar rats by intraductal 5% taurocholate injection. To evaluate the effect of albumin on lung damage, animals received IV saline or human albumin immediately after AP (Groups: Saline and Albumin). To evaluate the effect of iNOS inhibition on lung damage, SMT was given immediately after AP (Group Saline+SMT, and Group Albumin+SMT). At 12 h after AP induction, serum amylase activity, lung vascular permeability and myeloperoxidase (MPO) activity were evaluated. Lung and pancreas histological analysis were performed.Serum amylase activity, pancreatic edema, lung vascular permeability, MPO activity, and inflammatory infiltration were significantly increased after AP. Albumin administration increased lung vascular permeability, inflammatory infiltration, and pancreatic edema compared to saline administration (p 0.05). Albumin administration with SMT reduced lung vascular permeability, MPO activity, and inflammatory infiltration compared to albumin administration alone (p 0.05).Lung and pancreatic damage induced by albumin administration for restoration of plasma volume in AP are reduced by iNOS inhibition. Awareness of this fact may be useful in high-risk patients who need to receive albumin for volume replacement.

Background Ischemia and reperfusion (I/R) causes tissue damage and intracellular calcium levels are a factor of cell death. Sodium calcium exchanger (NCX) regulates calcium extrusion and Trisulfated Disaccharide (TD) acts on NCX decreasing intracellular calcium through the inhibition of the exchange inhibitory peptide (XIP). Objectives The aims of this research are to evaluate TD effects in liver injury secondary to I/R in animals and in vitro action on cytosolic calcium of hepatocytes cultures under calcium overload. Methods Wistar rats submitted to partial liver ischemia were divided in groups: Control: (n = 10): surgical manipulation with no liver ischemia; Saline: (n = 15): rats receiving IV saline before reperfusion; and TD: (n = 15): rats receiving IV TD before reperfusion. Four hours after reperfusion, serum levels of AST, ALT, TNF-alpha, IL-6, and IL-10 were measured. Liver tissue samples were collected for mitochondrial function and malondialdehyde (MDA) content. Pulmonary vascular permeability and histologic parameters of liver were determined. TD effect on cytosolic calcium was evaluated in BRL3A hepatic rat cell cultures stimulated by thapsigargin pre and after treatment with TD. Results AST, ALT, cytokines, liver MDA, mitochondrial dysfunction and hepatic histologic injury scores were less in TD group when compared to Saline Group (p

Administration of hypertonic saline (HS) solution to rats with acute pancreatitis (AP) decreases mortality and systemic inflammation. We hypothesized that these effects are related not only to systemic inflammatory reduction, but also to a reduction of the pancreatic lesion. Acute pancreatitis was induced in Wistar rats by injection of 2.5% sodium taurocholate. Animals were divided in groups: without AP, not treated AP, AP treated with NaCl 0.9%, and AP treated with NaCl 7.5%. Trypsinogen activation peptides and amylase activity were increased in ascitic fluid and serum and were not affected by treatment with HS. Pancreatic inflammation was evaluated by increased myeloperoxidase activity, malondialdehyde formation, and histopathology for severity of pancreatic lesions. The HS did not affect these parameters. Expression of cyclooxygenase 2 and inducible nitric oxide synthase was markedly increased in the pancreas of the AP group and was reduced by treatment with HS. This treatment also reduced the levels of TNF-α and IL-6 but not of IL-10 in the pancreatic tissue. These results show that HS modulates cytokine production and expression of enzymes responsible for inflammatory mediator production in the pancreas without affecting the severity of the pancreatic lesions.

Intestinal and pancreaticobiliary types of Vater’s ampulla adenocarcinoma have been considered as having different biologic behavior and prognosis. The aim of the present study was to determine the best immunohistochemical panel for tumor classification and to analyze the survival of patients having these histological types of adenocarcinoma. Ninety-seven resected ampullary adenocarcinomas were histologically classified, and the prognosis factors were analyzed. The expression of MUC1, MUC2, MUC5AC, MUC6, CK7, CK17, CK20, CD10, and CDX2 was evaluated by using immunohistochemistry. Forty-three Vater’s ampulla carcinomas were histologically classified as intestinal type, 47 as pancreaticobiliary, and seven as other types. The intestinal type had a significantly higher expression of MUC2 (74.4% vs. 23.4%), CK20 (76.7% vs. 29.8%), CDX2 (86% vs. 21.3%), and CD10 (81.4% vs. 51.1%), while MUC1 (53.5% vs. 82.9%) and CK7 (79.1% vs. 95.7%) were higher in pancreatobiliary adenocarcinomas. The most accurate markers for immunohistochemical classification were CDX2, MUC1, and MUC2. Survival was significantly affected by pancreaticobiliary type (p = 0.021), but only lymph node metastasis, lymphatic invasion, and stage were independent risk factors for survival in a multivariate analysis. The immunohistochemical expression of CDX2, MUC1, and MUC2 allows a reproducible classification of ampullary carcinomas. Although carcinomas of the intestinal type showed better survival in the univariate analysis, neither histological classification nor immunohistochemistry were independent predictors of poor prognosis.

Os somatostatinomas são tumores neuroendócrinos extremamente raros quepossuem positividade imunohistoquímica para somatostatina. A incidência destes tumores émaior nos pacientes portadores da síndrome de Von Recklinghausen. Existem quatro casosrelatados na literatura que mostram coexistência entre somatostatinoma e tumores do estroma gastrointestinal (GIST), todos em pacientes com neurofibromatose. Neste relato, descrevemosuma paciente não portadora da síndrome que apresentou dois somatostatinomas primários de papila maior e menor e nove nódulos jejunais de GIST. O diagnóstico foi confirmado pelo anátomo-patológico e imunohistoquímica, e o tratamento consistiu em uma duodenopancreatectomia associada à ressecção dos nódulos jejunais. A paciente evoluiu com gastroparesia no pós-operatório, e recebeu alta no 34º PO com aceitação de dieta oral. Este é o primeiro caso de toda a literatura que descreve apresentação simultânea destes tumores em paciente não portadora de neurofibromatose.

Objective. Acute pancreatitis is one the important causes of systemic inflammatory response syndrome (SIRS). SIRS results in gut barrier dysfunction that allows bacterial translocation and pancreatic infection to occur. Indomethacin has been used to reduce inflammatory process and bacterial translocation in experimental models. The purpose of this study was to determine the effect of inhibition of prostaglandin E2 (PGE2) production on pancreatic infection. Materials and methods. An experimental model of severe acute pancreatitis (AP) was utilized. The animals were divided into three groups: sham (surgical procedure without AP induction); pancreatitis (AP induction); and indomethacin (AP induction plus administration of 3 mg/kg of indomethacin). Serum levels of interleukin (IL)-6 and IL-10, PGE2, and tumor necrosis factor (TNF)-α were measured 2h after the induction of AP. We analyzed the occurrence of pancreatic infection with bacterial cultures performed 24h after the induction of AP. The occurrence of pancreatic infection (considered positive when the CFU/g was >105), pancreatic histologic analysis, and mortality rate were studied. Results. In spite of the reduction of IL-6, IL-10, and PGE2 levels in the indomethacin group, TNF-α level, bacterial translocation, and pancreatic infection were not influenced by administration of indomethacin. The inhibition of PGE2 production did not reduce pancreatic infection, histologic score, or mortality rate. Conclusion. The inhibition of PGE2 production was not able to reduce the occurrence of pancreatic infection and does not have any beneficial effect in this experimental model. Further investigations will be necessary to discover a specific inhibitor that would make it possible to develop an anti-inflammatory therapy.

To evaluate if using a soft-tipped guidewire to cannulate the common bile duct may ameliorate development of post-ERCP pancreatitis and facilitate cannulation of the CBD.A single-center, blinded, randomized trial of conventional cannulation technique using sphinctertome and contrast injection versus guidewire cannulation technique.We prospectively randomized 300 patients to conventional cannulation (group I) or guidewire cannulation (group II) technique.Primary outcome measure was incidence of acute pancreatitis and secondary outcome measures were ease of cannulation of common bile duct (assessed by attempts required for common bile duct cannulationrates of precut sphincterotomy) and overall complication rates.Guidewire cannulation was associated with significantly lower likelihood of post-ERCP pancreatitis (adjusted OR 0.43, 95% CI 0.21-0.89, P= 0.02). Twenty-five patients (16.6%) in group I and thirteen patients (8.6%) in group II developed acute pancreatitis, P= 0.037. All instances of pancreatitis were mild. There were more women in group II; 41 in group I and 59 in group II, P= 0.028. Otherwise the two groups were comparable for age, age under 35 yr, indication for ERCP, diagnosis, and number of patients with SOD. The number of patients requiring 0-3, 4-6, and 7-10 attempts for successful cannulation of the common bile duct were 87, 48, and 15 in group I and 117, 24, and 9 in group II, respectively, P= 0.001. A total of 33 patients in group I and 13 patients in group II required precut sphincterotomy, P= 0.007. Rates of accidental pancreatic duct cannulation were 21 in group I and 27 in group II, P= 0.34. Rates of overall complication were not significantly different in the two groups.Guidewire technique for bile duct cannulation lowers likelihood of post-ERCP pancreatitis by facilitating cannulation and reducing need for precut sphincterotomy.

Both endoscopic and surgical drainage procedures are effective palliative methods for malignant biliary obstruction. Surgical drainage is still preferred in developing countries due to the high cost of procuring metal biliary stents. The aim of this study was to evaluate the quality of life and the cost of care in patients with metastatic pancreatic cancer after endoscopic biliary drainage and surgical drainage.This is a prospective, randomized controlled trial conducted in a tertiary referral center in Brazil. Patients with biliary obstruction due to metastatic pancreatic cancer and liver metastasis, but without gastric outlet obstruction, were included in the study. Endoscopic biliary drainage with the insertion of a metal stent into the bile duct was compared with the surgical drainage procedure (choledochojejunostomy and gastrojejunostomy). Quality of life was assessed before, and 30 days, 60 days, and 120 days after the drainage procedure. The cost of drainage procedure, cost during the first 30 days and the total cost from drainage procedure to death were calculated.Of the 273 patients with pancreatic malignancy seen at our hospital between July 2001 and October 2004, 35 patients were eligible for the study, and 30 agreed to participate in the study. Both surgical and endoscopic drainage procedures were successful, without any mortality in the first 30 days. The cost of biliary drainage procedure (US dollars 2,832 +/- 519 vs 3,821 +/- 1,181, p= 0.031), the cost of care during the first 30 days after drainage (US dollars 3,122 +/- 877 vs 6,591 +/- 711, p= 0.001), and the overall total cost of care that included initial care and subsequent interventions and hospitalizations until death (US dollars 4,271+/- 2,411 vs 8,321 +/- 1,821, p= 0.0013) were lower in the endoscopy group compared with the surgical group. In addition, the quality of life scores were better in the endoscopy group at 30 days (p= 0.042) and 60 days (p= 0.05). There was no difference between the two groups in complication rate, readmissions for complications, and duration of survival.Endoscopic biliary drainage is cheaper and provides better quality of life in patients with biliary obstruction and metastatic pancreatic cancer.

The immune function is altered in jaundiced patients; here, the ability of their peripheral blood mononuclear cells to perform phagocytosis and to release H2O2 was analyzed.Cells from 53 patients before surgery for relief of cholestasis, from 38 patients 1 week and from 15 patients 2 weeks after surgery were separated and cultured for 1 h in the presence of phorbol myristate acetate. H2O2 release was evaluated colorimetrically and phagocytosis by the ingestion of Escherichia coli in vitro.Before surgery for relief of cholestasis, the cells of the patients were unable to release H2O2, but, after surgery, an increasing percentage of patients had cells that were able to produce H2O2 (13% after 1 week; 33% after 2 weeks). This recovery did not correlate with bilirubinemia. When cultured for 1 week in the presence of normal or jaundiced plasma, regardless of collection time, cells of 12/12 patients released H2O2, but in lower levels if in the presence of jaundiced plasma. In contrast, H2O2 release by normal donor cells was enhanced in the presence of jaundiced plasma. Phagocytosis by cells of the patients was lower, but when present was associated with a significantly higher bactericidal activity.These significant, but reversible alterations of monocyte function in jaundiced patients might contribute to their enhanced susceptibility to surgical complications.

Severe acute pancreatitis (AP) is characterized by hemodynamic alterations and a systemic inflammatory response, leading to a high mortality rate. Treatment of hemorrhagic shock with hypertonic saline solutions significantly reduces mortality through an improvement in the hemodynamic conditions and possibly by an anti-inflammatory effect. Therefore, hypertonic solutions could be effective in AP.Wistar rats were divided in 4 groups: group C, control, without AP; group NT, AP, without treatment; group NS, treatment with normal saline solution (NaCl 0.9%) 1 hour after AP; group HTS, treatment with hypertonic saline solution (NaCl 7.5%) 1 hour after AP. AP was induced by injection of 2.5% sodium taurocholate into the pancreatic duct. Mean arterial blood pressure (MAP) and heart rate were recorded at 0 and 2, 4, 24, and 48 hours after AP. After induction of AP, animals were killed at 2, 12, 24, and 48 hours for serum amylase, interleukin (IL)-6, and IL-10 analysis, pancreatic tissue culture and histologic analysis, oxidation and phosphorylation of liver mitochondria, pulmonary myeloperoxidase activity (MPO), and mortality study.In animals of groups NS and NT, a significant decrease of MAP was observed 48 hours after AP (NS: 91 +/- 3 mm Hg; NT: 89 +/- 3 mm Hg) compared with baseline (C: 105 +/- 2 mm Hg) and to HTS group (HTS: 102 +/- 2 mm Hg; P0.05). In animals of group NT, NS, and HTS, serum IL-6 and IL-10 levels were significantly higher at 2 hours after AP compared with the control group. However, IL-6 levels at 12 hours after AP and IL-10 levels at 2 and 12 hours after AP were significant lower in group HTS compared with NS and NT groups (P0.05). In group HTS, a decrease of pulmonary MPO activity and of pancreatic infection was observed 24 hours after AP compared with NT and NS groups (P0.05). A significant reduction on pancreatic acinar necrosis and mitochondrial dysfunction was observed after 48 hours of AP in animals of group HTS compared with groups NT and NS (P0.05). A significant reduction on mortality was observed in HTS (0/14) compared with NS (6/17; 35%) and NT (7/20; 35%).The administration of hypertonic saline solution in experimental AP attenuated hemodynamic alterations, decreased inflammatory cytokines, diminished systemic lesions and pancreatic acinar necrosis, prevented pancreatic infection, and reduced the mortality rate.

Colorectal cancer invading adjacent organs is a frequent event occurring in 5.5% to 12% of all colorectal malignancies. Colon cancer directly invading the duodenum and pancreas is rare and may require combined resection of the colon, pancreas, and duodenum, which represents a complex operation with significant morbidity and mortality rates. In this article, a case of a 41-year-old patient with a right colon cancer directly infiltrating the duodenum and head of the pancreas is presented. The patient was treated by radical combined resection of the colon, duodenum, and pancreas. Pathological examination confirmed neoplastic invasion of the adjacent organs and absence of lymph node metastasis (T4N0). The patient recovered uneventfully. Patients with colorectal cancer infiltrating adjacent organs such as the duodenum and the pancreas should be treated by radical en bloc resection of the tumor. This procedure is the preferred treatment strategy because it seems to be associated with improved overall survival rates.

An experience with the diagnosis and treatment of patients with non-Oriental primary intrahepatic lithiasis (PIHL) is described. A group of 48 native Brazilian patients with symptomatic PIHL were studied, and the patients' characteristics, diagnoses, treatment protocols based on the presentation of the disease, prognostic factors, and late results were analyzed. Liver resection was performed in patients with an irreversible lesion, such as parenchymal atrophy or biliary stenosis; and biliary drainage procedures were employed in patients with bilateral disease. Late results were considered good when no postoperative symptoms were observed and poor if there was pain recurrence or cholangitis. Overall good results were observed in 73.4% of the patients. Good late results were observed in 94.1% and 62.1% of the patients with unilateral and bilateral stones, respectively. None of the analyzed parameters (gender, age, previous biliary surgery, bilirubin level, serum leukocyte counts, prothrombin activity, previous history of cholangitis, stone location) predicted poor late results, but the risk for patients with bilateral stones to develop late complications was 7.2 times higher than for those with unilateral disease. Non-Oriental PIHL is a rare disease, and the patients' characteristics are similar to those of patients with Oriental PIHL. We believe that personalized treatment based on the presentation of the disease led to the high incidence of good late results in this series.

Annular pancreas (AP) is a rare congenital anomaly, usually present in childhood, with symptoms due to duodenal obstruction; however, this condition can manifest in adulthood with abdominal pain, pancreatitis and pancreatic head mass. The authors present a case of AP observed in a 22-year-old patient that presented an unusual dual-phase clinical manifestation of duodenal obstruction in infancy that was treated by a duodenojejunostomy, and abdominal pain due to chronic pancreatitis in the adult age. MRI with cholangiopancreatography played a decisive role in achieving the correct diagnosis. The patient was treated by a pylorus-preserving Whipple procedure, with resection of the previous duodenojejunostomy. Pancreatic changes characteristic of chronic pancreatitis were demonstrated both in the AP and in the resected pancreatic segment. A marked biliopancreatic ductal anomaly not previously described in the literature was demonstrated by radiologic examination of the surgical specimen. The pathogenesis of AP, the importance of its association with benign and malignant pancreatic disease and the treatment alternatives are discussed by the authors.

Os tumores neuroectodermicos primitivos (PNETs) sao pequenas celulas redondas de tumores malignos classificadas como parte da familia do sarcoma de Ewing e representa aproximadamente 1% de todos as sarcomas1. Predominantemente ocorrendo em tecidos moles, ao longo das extremidades, eles tambem tem sido relatados em uma variedade de orgaos, tais como rim, bexiga, testiculo, ovario, utero, coracao e pulmao2,3. PNETs pancreaticos (PPNET) sao extremamente raros e precisam ser distinguidos de carcinomas neuroendocrinos, carcinoma indiferenciado de celulas pequenas, pancreatoblastomas e tumores pancreaticos. O conhecimento sobre PPNET e escasso; apenas 17 relatos podem ser encontrados na literatura. Aqui e descrito o caso de uma mulher de 25 anos com uma massa solida-cistica na cabeca do pâncreas, que mais tarde revelou ser PPNET.

The management of patients with chronic pancreatitis (CP) remains a challenging problem. Main indications for surgery are intractable pain, suspicion of malignancy, and involvement of adjacent organs. The main goal of surgical treatment is improvement of patient quality of life. The surgical treatment approach usually involves proximal pancreatic resection, but lateral pancreaticojejunal drainage may be used for large-duct disease. The newer duodenum-preserving head resections of Beger and Frey provide good pain control and preservation of pancreatic function. Thoracoscopic splanchnicectomy and the endoscopic approach await confirmatory trials to confirm their efficiency in the management of CP. Common bile duct obstruction is addressed by distal Roux-en-Y choledochojejunostomy but when combined with dudodenal obstruction must be treated by pancreatic head resection. Pancreatic ascites due to disrupted pancreatic duct should be treated by internal drainage. The approach to CP is multidisciplinary, tailoring the various therapeutic options to meet each individual patient's needs.

INTRODUCTION Some studies demonstrate the crucial role of proteases in the pathogenesis of acute pancreatitis (AP). Systemic release of proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) has been demonstrated in AP, yet the mechanism of activation remains unclear. Furthermore, it is not known if the amount of pancreatic enzyme in the pancreas determines the production of proinflammatory cytokines. AIM To determine whether there is a link between the pancreatic enzyme content and the production of cytokines and consequently the systemic lesions observed in AP. METHODOLOGY Forty-seven animals were divided into three groups: group I had a high pancreatic enzyme level (with and without AP), group II had a low pancreatic enzyme level (cerulein infusion: 0.133 microg x kg(-1) x h(-1)) (with and without AP), and group III were the controls. AP was induced by injection of 5% sodium taurocholate into the pancreatic duct. To evaluate the pancreatic enzyme contents before AP, trypsinogen and amylase analysis was carried out on pancreatic tissue collected after the animals were killed. Two hours after induction of AP, concentrations of pancreatic enzymes and trypsinogen activation peptide (TAP) in serum, ascitic fluid, and pancreatic tissue were determined. The ascitic fluid was assayed for TNF-alpha and the serum was assayed for IL-6 with ELISA kits. Systemic lesions were sought on the basis of hepatic mitochondrial respiratory function measured polarographically. RESULTS AND CONCLUSION The administration of physiological doses of cerulein diminishes the pancreatic enzyme and TAP levels, the production of proinflammatory cytokines, and the liver mitochondrial dysfunction observed in AP, suggesting that the pancreatic enzyme content is an important factor in the severity of AP.

Cystic neoplasms of the pancreas are uncommon lesions but are becoming increasingly prevalent. Herein we report a case of an oligolocular cystic lesion in the head of the pancreas in a young female that had undergone a cystenteroanastomosis 10 years ago. She underwent a duodenopancreatectomy with an uneventful recovery. The histology showed a serous oligocystic adenoma of the pancreas and the immunohistochemistry study confirmed the diagnosis. There is no sign of recurrence after the surgery. The role of pre-operative diagnosis based on tomographic, echoendoscopy and fine needle aspiration are discussed.

Bacterial translocation is an important source of pancreas infection in acute pancreatitis. The effect of platelet-activating factor (PAF) in the pathogenesis of acute pancreatitis has been proved in various studies. The aim of this study was to determine whether potent PAF antagonists influence bacterial translocation in acute pancreatitis. Acute pancreatitis was induced in 62 Wistar rats by injection of 2.5% sodium taurocholate into the biliopancreatic duct. The rats treated with PAF factor antagonists received intravenous injection of WEB-2170 (10 mg/kg), lexipafant (5 mg/kg), and BN-52021 (5 mg/kg) 30 minutes before induction of acute pancreatitis. Six hours after induction of acute pancreatitis, bacteriologic cultures and histologic scoring of tissues were performed. There was a statistically significant reduction in bacterial translocation to the mesenteric lymph nodes and liver but not to the pancreas of the rats treated with PAF antagonists. No significant increase in the intestinal bacterial population of any group was found. There were no statistical differences between the pancreatic histologic scores of the groups. PAF antagonists reduced bacterial translocation to distant sites other than the pancreas, preventing the bacterial dissemination that occurs in the early phase of acute pancreatitis and may have beneficial effects on the evolution of this disease.

Background: The low incidence of pancreatic leiomyosarcoma is responsible for the small number of cases correctly diagnosed preoperatively, the tumor being frequently confused with benign pancreatic lesions. Results: We describe a symptom free 52-yr-old male bearing an abdominal mass incidentally found at physical examination. Imaging techniques revealed a nonhomogenous large mass at the head of the pancreas that dislodged the portal vein and the superior mesenteric vein. Increased metabolic activity in the tumor area demonstrated by 18F-fluorodeoxyglicose positron emission tomography scan allowed the diagnosis of a malignant lesion. The patient was operated on and a pylorus preserving pancreatoduodenectomy performed. The pathology diagnosis was a low grade leiomyosarcoma. Immunohistochemistry revealed positivity for vimentin and smooth muscle specific actin. The clinical course was uneventful after 2 yr follow-up. Conclusion: Pancreatic leiomyosarcoma may be preoperatively diagnosed by image techniques and differentiated from benign lesions by means of fluorodeoxyglicose positron emission tomography scanning (FDGPET).

A maioria dos pacientes com câncer de pâncreas apresenta estdios avançados e é tratada paliativamente. Dos que são submetidos exclusivamente a derivação biliar, cerca de 30%-50% vão apresentar na evolução necessidade de tratamento de obstrução duodenal. As técnicas atualmente empregadas para derivação gástrica podem acarretar vômitos pós-operatórios, principalmente quando feitas profilaticamente. Uma nova técnica foi planejada para evitar alterações no mecanismo de esvaziamento gátrico e a recirculação do conteúdo alimentar. Esta técnica consta de anastomose gastrojejunal entre o corpo gátrico e a primeira alça jejunal tipo Braun em que a alça aferente é bloqueada evitando o ciclo vicioso alimentar. A reconstituição do trânsito alimentar é feita a jusante desta anastomose, impedindo o refluxo biliar para o estômago. Dezenove pacientes foram tratados consecutivamente sem complicações. A sonda nasogástrica foi retirada em torno do terceiro dia de pós-operatório e iniciada realimentação no dia seguinte. Não se observaram vômitos no pós-operatório imediato ou tardio em decorrência de retardo do esvaziamento gátrico. Pancreatic cancer is most often diagnosed too late for curative resection. Therefore most of patients with pancreatic cancer are only submitted to palliative procedures. From those submitted to biliary bypass alone about 30 % need treatment for gastric obstruction at some point of the follow up. Surgical techniques for gastroenterostomy currently in use carry themselves delaying in the gastric emptying mechanisms and circulus vitiosus through the non obstructed duodenum. The objetive of this paper is to describe a new technique devised to avoid those problems and to improve the functional results of prophylatic gastroenterostomy. This was accomplished by a gastrojejunostomy in the upper body of the stomach and constructing the jejunal loop in a Braun fashion, whose afferent loop is blocked. The main features of this technique are the position of the gastroenterostomy with a low distubance of gastric motility and the construction of the jejunal loop in order to avoid the circulus vomiting. Nineteen patients were consecutively submitted to this procedure and no post operative complications were observed. Nasogastric tube was taken off in about three days and oral feeding resumed the next day. Vomits were not observed neither in the early post operative period nor in the long term follow up. This newly designed type of reconstruction is a effective gastric beypass and avoids the problem of food reentry.

A 50-year-old woman presented with pancreatitis, fluctuant jaundice, weight loss, and abdominal pain. Contrast-enhanced computed tomography and abdominal ultrasound showed slight dilatation of the biliary tree and gallbladder without calculi. Endoscopy demonstrated a tumor protruding from the papilla of Vater. First endoscopically biopsy diagnosed no tumor, and a second biopsy diagnosed as papillary adenocarcinoma. The patient underwent duodenopancreatectomy. The specimen was fixed in formalin (10%). The tissue was processed routinely, and paraffin sections were stained with hematoxylin-eosin and periodic acid Schiff. Gross examination showed two tumors seen as prolapsed nodules growing isolated from the minor and major duodenal papillae measuring 1.5 and 1.0 cm, respectively, both covered by duodenal mucosa and the histologic study of both lesions demonstrated a moderately differentiated tubular adenocarcinoma, which invaded duodenal wall. After surgery, she is alive 24 months without evidence of recurrence.

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Objectives: Intraperitoneal administration of trypsin stimulates the production of cytokines from peritoneal macrophages. Removing the pancreatitis-associated ascitic fluid from the peritoneal cavity may decrease the systemic inflammatory response in acute pancreatitis (AP). We investigated the effect of peritoneal lavage on the systemic inflammatory response in severe AP. Methods: Acute pancreatitis was induced in Wistar rats by 5% taurocholate intraductal injection. Peritoneal lavage was performed for 4 hours after onset of AP. At 4 hours after induction of AP, serum samples were assayed for amylase and inflammatory cytokines (tumor necrosis factor >, interleukin-6 [IL-6], and IL-10). Expression of pancreatic cyclooxygenase-2 and inducible nitric oxide synthase, liver mitochondrial function, and pulmonary myeloperoxidase activities were determined. Results: Peritoneal lavage after AP led to a decrease in serum levels of tumor necrosis factor > and IL-6 and an increase in IL-10. In the pancreas, this treatment reduced cyclooxygenase-2 and inducible nitric oxide synthase expression. Liver mitochondrial dysfunction was also reduced. There were no differences on serum amylase levels and pulmonary myeloperoxidase between groups with AP. Conclusions: Peritoneal lavage has a systemic anti-inflammatory effect in severe AP and may be able to decrease the severity of severe AP.

Severe acute pancreatitis is associated with high morbidity and mortality rates. At the present time, no specific therapy has been shown to be uniformly effective in reducing morbidity and mortality in this disease. The aim of this study was to determine the effects of pentoxifylline on the pancreatic and systemic inflammatory process, pancreatic infection, and mortality rate in severe acute pancreatitis in rats.One hundred and twenty male Wistar rats were divided into 3 groups: sham, pancreatitis, and pentoxifylline (acute pancreatitis induction plus administration of 25 mg/kg pentoxifylline). Inflammatory response was measured by histological studies, inflammatory cytokine production (IL-6, IL-10, and TNF-alpha), and mortality rate. Pancreatic infection was evaluated by bacterial cultures expressed in colony-forming units per gram.Pentoxifylline-treated animals had a statistically significant reduction of inflammatory cytokine levels, pancreatic histological damage, occurrence of bacterial translocation and pancreatic infection (p0.05), associated with a significant reduction in mortality rate.Pentoxifylline administration in this experimental model of acute pancreatitis reduces local and systemic inflammatory responses and decreases the pancreatic infection and the mortality rate.

Objective: Endoscopic sphincterotomy (ES) may facilitate insertion of self expandable metal stent (SEMS) and also help avert the development of pancreatitis from stent-related occlusion of the pancreatic duct. On the other hand, ES is also independently associated with pancreatitis, bleeding, and perforation. We evaluated whether ES before SEMS placement was associated with a greater likelihood of stent migration and other complications in patients with malignant obstruction of the distal common bile duct. Methods: Seventy-four patients with unresectable distal bile duct obstruction were prospectively randomized to biliary stenting following ES (group 1) and without ES (group 2). Main outcome measures included overall procedure complications rates including stent migration, stent occlusion, oxygen desaturation, bleeding, perforation, and pancreatitis. Results: Covered SEMS were successfully deployed in all patients in both groups. Stent migration occurred in 6 patients (16%) in group 1 and 1 patient (3%) in group 2, P = 0.075. Overall, complications occurred in 18 patients in group 1 and 4 patients in group 2, P = 0.006. There was no pancreatitis in either group. Conclusions: Deployment of covered SEMS without prior ES in patients with distal common bile duct obstruction owing to pancreatic cancer is feasible and prevents the development of complications such as stent migration, bleeding, and perforation.

Objectives The accuracy of endoscopic ultrasound-fine needle aspiration cytology (EUS-FNAC) for the diagnosis of pancreatic cancer is suboptimal. Mutational activation of the kras oncogene is almost universally present in pancreatic cancer tissue. We, therefore, investigated if analysis for mutant kras gene in the EUS-FNAC aspirates supplements cytopathology for the diagnosis of pancreatic adenocarcinoma (PAC). Methods EUS-FNAC specimens obtained from 74 patients with pancreatic masses were analyzed for the presence of kras mutation on codon 12 using polymerase chain reaction-restriction fragment length polymorphism and MvaI restriction enzyme. Definitive diagnosis was based on surgical pathology or long-term follow-up (median 27.8 mo); 57 patients had PAC, 11 patient's chronic pancreatitis, and 9 patient's nonfunctioning neuroendocrine tumors. Results Analysis of mutant kras gene in addition to cytopathology allowed the detection of PAC in 4 additional patients as compared with cytopathology alone. Cytopathology and kras mutant analysis were negative for PAC in 17 patients of whom 6 patients (35%) had PAC. The respective sensitivity (90.9% vs. 82.5%), specificity (47.6% vs. 97.9%), positive predictive value (89.5% vs. 83.8%), negative predictive value (98.1% vs. 94.1%), accuracy (89.2% vs. 58.8%) of cytopathology plus kras mutation versus cytopathology were numerically superior but did not reach statistical significance. Conclusions Analysis for the presence of mutant kras gene supplements conventional cytopathology for the diagnosis of PAC even without a cytopathologist in attendance and using only 3 needle passes. Among patients with negative cytopathology, the presence of kras mutation represents pancreatic cancer while the absence of kras mutation increases the possibility of benign lesion.

Obesity and diabetes mellitus (DM) are associated with pancreatic cancer. The present study evaluated tumor staging and resection of pancreatic adenocarcinoma (PaC) according to previous Body Mass Index (BMI), BMI on admission and DM duration.A retrospective analysis of 151 consecutive patients with PaC was performed: 73 were evaluated according to BMI preceding tumor-related weight loss and BMI on admission; 118 according to DM diagnosis; and 38 were assessed according to DM duration (less than 1 year [recent-onset] versus more than 2 years [long-standing]).There was no difference in the prevalence of tumor stage III or IV between previously normal weight and overweight/obese patients (56 vs. 42%, NS). Tumor resection rate was higher in previously obese than in previously lean patients (58 vs. 24%, p0.05). Tumor staging and resection were similar between normal weight and overweight/obese patients considering BMI on admission and diagnosis of DM. Weight loss was more pronounced in diabetic than in non-diabetic patients (21.7 vs. 13.3%, p0.01). Tumor staging and resection were similar between recent-onset and long-standing diabetic patients.Tumor resection rate was lower in previously normal weight patients. Diabetics lost more weight than non-diabetic patients. Neither BMI on admission nor the presence of DM nor DM duration influenced tumor staging or resection in PaC patients.

BACKGROUND: The standard treatment for acute pancreatitis (AP) is still based on supportive care. The search for a new drug that could change the natural history of the disease is a continuing challenge for many researchers. The aim of this study is to evaluate the effect of a cyclooxygenase-2 (COX-2) inhibitor on experimental AP in rats. METHODS: The animals were divided into 2 groups: Group 1 (n = 30)-animals with taurocholate-induced AP treated with parecoxib (40 mg/kg). Group 2 (n = 30)-animals with taurocholate-induced AP that received saline. The COX-2 inhibitor (parecoxib) was injected immediately after AP induction, through the penis dorsal vein. The parameters evaluated were histology, serum levels of amylase, IL-6 and IL-10, and mortality rate. RESULTS: The serum levels of IL-6 and IL-10 in the parecoxib-treated group were lower than the control group. The amylase serum levels and the mortality rate remained unchanged in the treated animals. Histologic morphology also was unaltered, except for fat necrosis, which was higher in parecoxib-treated rats. CONCLUSION: Inhibition of Cox-2 decreases the systemic release of inflammatory cytokines, but has a poor effect on the direct pancreas injury caused by taurocholate.

BACKGROUD: Recent studies indicate that hyperthermia can change inflammatory mechanisms and protect experimental animals from deleterious effects of secretagogue-induced acute pancreatitis AIM: To evaluate the effects of hyperthermia post-treatment on cerulein-induced acute pancreatitis in rats METHODS: Twenty animals were divided in two groups: group I (n = 10), rats with cerulein-induced acute pancreatitis undergone hyperthermia, and group II (n = 10), animals with cerulein-induced acute pancreatitis that were kept normothermic. In all groups, amylase serum levels, histologic damage, vascular permeability and pancreatic water content were assessed. Acute pancreatitis was induced by administration of two cerulein injections (20 mcg/kg). A single dose of Evans' blue dye was administered along with the second dose of cerulein. All animals also received a subcutaneous injection of saline solution. After this process, animals undergone hyperthermia were heated in a cage with two 100 W lamps. Body temperature was increased to 39.5ºC and maintained at that level for 45 minutes. Normothermia rats were kept at room temperature in a second cage RESULTS: Control animals had typical edema, serum amylase activity and morphologic changes of this acute pancreatitis model. Hyperthermia post-treatment ameliorated the pancreatic edema, whereas the histologic damage and the serum amylase level remained unchanged CONCLUSIONS: The findings suggest a beneficial effect of the thermal stress on inflammatory edema in experimental acute pancreatitis.

Background: The current study sought to evaluate the results of liver resection as the treatment for unilateral non-oriental primary intrahepatic lithiasis (PHIL). Methods: Twenty-seven symptomatic patients (mean age 42 years) were submitted to liver resection; the indications were parenchymal fibrosis/atrophy in 22 and biliary stenosis in 5. Resection was associated with a Roux-en-Y hepaticojejunostomy in patients with a significant degree of dilation of the extrahepatic biliary duct. Results: There was no operative mortality and the morbidity rate was 7.4% (2 patients with biliary fistula). After a median follow-up of 41.2 months, the overall rate of good results was 92.6%. All patients submitted to liver resection alone presented good late results, while 80% of those with associated hepaticojejunostomy did not have complications (P .12). Late complications were observed in 2 patients (7.4%): 1 with a liver abscess and 1 with cholangitis and recurrent stones. There was no mortality during long-term follow-up. Conclusions: Liver resection showed low incidence of complications and good long-term results. None of the patients with unilateral disease without associated extrahepatic bile duct dilation presented complications and they were considered cured. We believe that resection indications should be expanded and the procedure should be indicated as routine in patients with unilateral PHIL even in the absence of parenchymal fibrosis/atrophy or biliary stenosis. © 2006 Excerpta Medica Inc. All rights reserved.