Emilio Elias Abdo

Clinical and pathologic prognostic factors for curative resection for pancreatic cancer

BACKGROUND Pancreatic cancer is the fifth leading cause of cancer-related deaths in the world. Operative resection is the only therapeutic option with curative potential for this disease. OBJECTIVE The aim of the present study was to correlate clinical and pathologic parameters with survival in patients submitted to pancreatic resection for pancreatic adenocarcinoma. METHODS Surgical resection with curative intent (R0 and R1 resections) was performed in 65 pancreatic cancer patients between 1990 and 2006. The overall results of surgical treatment were retrospectively analyzed and compared with the clinicopathologic features of these patients. RESULTS Pylorus-preserving pancreatoduodenectomy was performed in 37 patients (56.9%), classic resection in 35.4%, distal pancreatectomy in 4.6% and total pancreatectomy in 3.6%. The inhospital mortality was 5% (three patients). Postoperative complications occurred in 28 patients (43%). Mean survival and five-year survival rate after curative resection were 27 months and 9.0%, respectively. Sex, TNM stage, tumor differentiation, neural invasion, tumor size and involvement of resection margin were significant prognostic factors on univariate analysis. Multivariate analysis showed tumor differentiation and neural invasion as prognostic factors. CONCLUSION Patients with pancreatic cancer, even those with poor prognostic factors should be given the opportunity of surgical resection with curative intent.

Effects of Octreotide Pretreatment in Experimental Acute Pancreatitis

Background: Severity of systemic lesions and mortality of experimental acute pancreatitis (AP) are reduced after pancreatic enzyme content reduction induced by cerulein administration. Octreotide has been used both prophylatically and therapeutically in AP. The possible effects of octreotide on pancreatic enzyme content and its influence on pulmonary lesions of experimental AP were assessed in this study. Methods: Wistar male rats were divided in two branches: Branch I – Animals divided into three groups: Group Sa (n = 10) intravenous saline infusion; Group Ce (n = 10) intravenous cerulein infusion, (0.133 µg/kg–1·h–1) and Group Oc (n = 10) SC octreotide (10 µg/kg–1). Trypsin, elastase and amylase pancreatic contents as well as serum amylase were determined thereafter in all three groups; Branch II – Rats treated as in branch I, were submitted to sodium taurocholate AP (Groups Sa+AP, Ce+AP and Oc+AP). Two hours thereafter amylase and TAP assays were performed in serum, ascites and pancreatic tissue in eight animals of each group. Pulmonary histology was studied by morphometry 24 h after AP in the remaining animals. Results: Increased serum amylase and pancreatic enzyme contents were observed in octreotide-treated animals when compared to animals receiving saline or cerulein. After AP increases of serum and ascitic fluid amylase and of pancreatic TAP were observed in octreotide pre-treated animals when compared to saline and cerulein groups. Pulmonary interstitial and alveolar edema after AP was significantly increased in rats receiving octreotide as compared to the cerulein group. Conclusion: Octreotide administration acutely increases the enzymatic content of the pancreas and thus may have a potential deleterious influence in the evolution of AP.

Influence of Pancreatic Enzyme Content on Experimental Acute Pancreatitis

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–&agr; (TNF-&agr;) 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 &mgr;g·kg−1·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-&agr; 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.

Effect of PAF antagonists on cerulein-induced pancreatitis

The present study was undertaken to investigate the involvement of PAF in acute pancreatitis induced by cerulein in rats. Cerulein (two doses of 20 micrograms/rat, the first s.c. and the second i.v., 1 h apart) induced a significant increase in vascular permeability in the pancreas, evaluated by the Evans blue (EB) extravasation method. Plasma amylase levels were also significantly increased in this group. The PAF antagonists, BN-52021 (5 mg/kg) and WEB-2170 (1 and 10 mg/kg), both significantly reduced the extravasation of EB in the pancrease induced by i.v. injection of PAF (1 microgram/kg). At these concentrations, BN-52021 was effective at inhibiting cerulein-induced pancreatitis (60-70% of inhibition) whereas WEB-2170 had no significant effect. Although the inhibition induced by BN-52021 suggests the involvement of PAF in cerulein-pancreatitis, the lack of effect of WEB-2170 reported here does not allow a definite conclusion. Further studies are needed to elucidate the differential effect of the PAF antagonists.

Tratamento cirúrgico dos insulinomas -- estudo de 59 casos

After establishing the diagnosis of an insulinoma the next step is its localization in order to perform the most suitable management approach. PURPOSE: To evaluate the methods used for the diagnosis of insulinoma and the localization of its site as well as the results of the surgical treatment. METHODS: Fifty nine consecutive patients with pancreatic insulinomas were studied. The discriminative power of the preoperative investigations in the localization of insulinomas was analysed. Special attention was focused to the intra operative methods of tumor localizations. The early and late results of the surgical treatment were also investigated. RESULTS: There were 55 benign cases and 4 malignant tumors. Preoperative localization was attempted by using ultrasonography (positive in 28.1%) CT imaging (positive in 25%), selective arteriography (positive in 54.1%), endoscopic ultrasonography (positive in 27.2%) and assay of portal plasma insulin levels (positive in 94.4%). In 54/55 cases (98.2%) the tumors were identified intraoperatively by palpation. By addition of intraoperative ultrasonography all lesions were identified and successfully removed without mortality. Five patients had multiple endocrine neoplasias all with multiple lesions in the pancreas. In patients with benign lesions 29 enucleations and 32 resections were performed. Pancreatic fistulas were the most common complication (29/59). Excluding the patients with malignant lesions the recovery rate was 98.1%. Three patients who underwent corporo caudal pancreactectomy developed diabetes. CONCLUSIONS: The preoperative localization is not necessary, since a combination of palpation and intraoperative ultrasonography can deal with most cases. Enucleation when possible is the best choice for benign lesions.

Prognostic significance of epidermal growth factor receptor overexpression in pancreas cancer and nodal metastasis.

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.

Protective effect of N2-mercaptopropionylglycine on rats and dogs liver during ischemia/reperfusion process

BACKGROUND N2-mercaptopropionylglycine is a powerful super oxide synthesis inhibitor and has been tested as a preventive agent of metabolic and structural hepatic damage in the ischemia/reperfusion process. AIM To analyze some effects of N2-mercaptopropionylglycine administration to animals of two species submitted to normothermic liver ischemia/reperfusion. MATERIAL AND METHODS Twenty-two rats and 22 dogs were divided into four groups: group I: rats that received intravenous saline 0.9%; group II: rats that received 100 mg/kg of N2-mercaptopropionylglycine; group III: dogs that received saline intravenous 0.9% and group IV: dogs that received 100 mg/kg N2-mercaptopropionylglycine. RESULTS Ten minutes after the saline or drug administration, each group was submitted to left lobe liver ischemia for 25 minutes followed by reperfusion. Biochemical studies 24 hours after reperfusion revealed a significantly lower elevation of transaminases in animals of groups II (AST = 271 +/- 182; ALT = 261 +/- 161 ) and IV (AST = 101 +/- 45; ALT = 123 +/- 89) when compared to the controls group: I (AST = 2144 +/- 966; ALT = 1869 +/- 1040 00) and III (AST = 182 +/- 76.51; ALT = 277 +/- 219), respectively. Histology study demonstrated a significantly minor aggression to animals of groups II and IV when compared to groups I and III, respectively. CONCLUSION These results suggest a significant release of free radicals of oxygen in the process and that N2-mercaptopropionylglycine may have a significant protective effect on liver parenchyma when submitted to ischemia/reperfusion.

Serous Oligocystic Adenoma of the Pancreas

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.

Trisulfate Disaccharide Decreases Calcium Overload and Protects Liver Injury Secondary to Liver Ischemia/Reperfusion.

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-α, 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<0.05) with no differences in pulmonary vascular permeability. In culture cells, TD diminished the intracellular calcium raise and prevented the calcium increase pre and after treatment with thapsigargin, respectively. Conclusion TD decreases liver cell damage, preserves mitochondrial function and increases hepatic tolerance to I/R injury by calcium extrusion in Ca2+ overload situations.