Rosely A. Patzina

Lymph Node Involvement and Not the Histophatologic Subtype Is Correlated with Outcome After Resection of Adenocarcinoma of the Ampulla of Vater

BackgroundIntestinal 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.MethodNinety-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.ResultsForty-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.ConclusionThe 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.

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.

Local and systemic effects of hypertonic solution (NaCl 7.5%) in experimental acute pancreatitis.

Objectives: 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. Methods: 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. Results: 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; P < 0.05). 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 (P < 0.05). 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 (P < 0.05). 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 (P < 0.05). A significant reduction on mortality was observed in HTS (0/14) compared with NS (6/17; 35%) and NT (7/20; 35%). Conclusions: 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.

Serpin Peptidase Inhibitor Clade A Member 1 as a Potential Marker for Malignancy in Insulinomas

Purpose: The biological behavior of insulinomas cannot be predicted based on histopathologic criteria in which the diagnosis of malignancy is confirmed by the presence of metastases. In this study, microarray and quantitative real-time reverse transcription-PCR were applied to identify differentially expressed genes between malignant and nonmalignant insulinomas to search for useful biomarkers to recognize the metastatic potential of insulinomas. Experimental Design: CodeLink human bioarrays were used to analyze differences in ∼20,000 genes between six well-differentiated endocrine tumors of benign behavior compared with one well-differentiated endocrine carcinoma (WDEC) and three metastases of endocrine carcinomas (MEC). Quantitative real-time reverse transcription-PCR was used to validate differential expressions of five genes in a series of 35 sporadic insulinomas. Serpin peptidase inhibitor clade A member 1 (SERPINA1; α-1-antitrypsin) expression, identified as up-regulated in malignant insulinomas, was also evaluated by immunohistochemistry. Results: Analysis of microarray data resulted in 230 differentially expressed genes. Gene Ontology analysis identified serine-type endopeptidase activity and serine-type endopeptidase inhibitor activity as pathways presenting significant differential expression. Protease serine 2 and complement factor B (from serine-type endopeptidase activity pathway) were respectively confirmed as up-regulated in well-differentiated endocrine tumors of benign behavior (WDET) and in WDEC/MEC. Angiotensinogen and SERPINA1 (from serine-type endopeptidase inhibitor activity pathway) were confirmed as up-regulated in WDEC/MEC. SERPINA1 was shown to be expressed in 85.7% of malignant versus 14.3% of nonmalignant insulinomas by immunohistochemistry. Conclusions: Our data are consistent to the possibility that SERPINA1 is a marker of malignancy in insulinomas. Given the widespread availability of antibody anti-α-1-antitrypsin in pathology services, SERPINA1 expression evaluation might be of clinical utility in recognizing patients more likely to develop an aggressive presentation.

MECHANISMS OF THE BENEFICIAL EFFECT OF HYPERTONIC SALINE SOLUTION IN ACUTE PANCREATITIS.

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-&agr; 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.

Inhibition of cyclooxygenase-2 in experimental severe acute pancreatitis

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.

Paradoxical reaction to treatment in 2 patients with severe acute paracoccidioidomycosis: a previously unreported complication and its management with corticosteroids.

Paradoxical reactions have never been described in patients with paracoccidioidomycosis or other deep endemic mycoses out of the context of human immunodeficiency virus infection. We describe 2 patients with an acute form of paracoccidioidomycosis who presented with a worsening of their clinical manifestations while on appropriate antifungal treatment. These manifestations were severe and required adjunct corticosteroid therapy.

Unusual clinical presentation of annular pancreas in the adult

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.

CO2 abdominal insufflation decreases local and systemic inflammatory response in experimental acute pancreatitis.

Objectives: Acute pancreatitis (AP) is a serious disease that is amplified by an associated systemic inflammatory response. We investigated the effect of CO2 pneumoperitoneum on the local and systemic inflammatory response in AP. Methods: Acute pancreatitis was induced in Wistar rats by 5% taurocholate intraductal injection. Carbon dioxide pneumoperitoneum was applied for 30 minutes before the induction of AP. Inflammatory parameters were evaluated in the peritoneum (ascites, cell number, and tumor necrosis factor &agr; [TNF-&agr;]), serum (amylase, TNF-&agr;, interleukin-6 [IL-6], and IL-10), pancreas (myeloperoxidase [MPO] activity, cyclo-oxygenase 2 and inducible nitric oxide synthase expression, and histological diagnosis), liver, and lung (mitochondria dysfunction and MPO activity). Results: Abdominal insufflation with CO2 before induction of AP caused a significant decrease in ascites volume, cells, and TNF-&agr; in the peritoneal cavity and in serum TNF-&agr; and IL-6 but not IL-10 levels. In the pancreas, this treatment reduced MPO activity, acinar and fat necrosis, and the expression of inducible nitric oxide synthase and cyclo-oxygenase 2. There were no significant differences on serum amylase levels, liver mitochondrial function, and pulmonary MPO between groups. Conclusions: Our data demonstrated that CO2 pneumoperitoneum reduced pancreatic inflammation and attenuated systemic inflammatory response in AP. This article suggests that CO2 pneumoperitoneum plays a critical role on the better outcome in patients undergoing laparoscopic pancreatic surgery.

Effect of inhibition of prostaglandin E2 production on pancreatic infection in experimental acute pancreatitis

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)-alpha were measured 2 h after the induction of AP. We analyzed the occurrence of pancreatic infection with bacterial cultures performed 24 h 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-alpha 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.