Edwin Parra

There were 49 patients studied, coming from The Liver Unit at the "Hospital das Clinicas da Faculdade de Medicina da USP (N=41) and from "Prof. Dr. Angelita Habr-Gama and Joaquim Gama-Rodrigues Surgery Institute", SP (N=8); all of which had hepatic metastasis of colorectal adenocarcinoma, with no evidence of concurrent metastasis in any other organs and were submitted to surgical treatment, during the period of 1992 to 2002, with the aim of analyzing the immunoexpression of the p53, ki-67, p16 and molecular markers in order to relate the disease-free period with the prognosis. The patient's clinical data were analyzed retrospectively for verification of information such as age, gender, size of the hepatic metastasis and/or the largest lesion, number of satellite nodules resected and compromised, margin of resection free from neoplasia. The immunoexpression of the p53 was associated with the shortest period of life free from disease (p = 0.04). The proliferation marker ki-67 was not associated with the reduction of the disease-free interval and survival; the immunoexpression of the proliferation marker p16 was not associated with the reduction of disease-free period and survival, however, it was associated with hepatic metastasis synchronism. In patients who received postoperative systemic chemotherapy with 5-FU and leucovorin, the immunoexpression on the hepatic metastasis was not associated with a longer disease-free interval. Molcular markers may be useful to evaluate hepatic metastasis of colorectal Adenocarcinoma.

Ramicotomy is a surgical procedure, with less adverse effects than conventional sympathectomy, however, it was abandoned due to the high recurrence rate. Twenty-eight pigs underwent bilateral videothoracoscopic ramicotomy and were divided into five groups. The animals were sacrificed at 15th, 45th, 90th, 135th and 180th postoperative days (POD). The segments were removed and evaluated for macroscopic regeneration and histological analysis. The data were compared to the control group of 10 intact segments of the sympathetic. There was no macroscopic regeneration on the 15th POD, and present on 41.6% on the 180th POD (P<0.05). The Schwann cells presented a similar evolution in both rami beginning at the 45th POD, with a smaller count in the gray rami. The collagen and reticular fibers presented a negative correlation (r=-0.414; P<0.01). The deposition of the collagen fibers was greater in the gray rami with a peak deposition on the 135th POD and a diminishing rate in the 180th P...

/ Thematic Poster Session / Tuesday, May 17/8:15 AM-4:30 PM / Area L, Hall B (Upper Level), C69 LUNG CANCER BIOMARKERS ... Hyaluronic Acid: A Potential Biochemical Marker For Diagnosis And Prognosis Of Patients With Lung Cancer ... , J. Maciel Martins , ER ...

To study the expression of COX-1 and COX-2 in the remodeled lung in systemic sclerosis (SSc) and idiopathic pulmonary fibrosis (IPF) patients, correlating that expression with patient survival. We examined open lung biopsy specimens from 24 SSc patients and 30 IPF patients, using normal lung tissue as a control. The histological patterns included fibrotic nonspecific interstitial pneumonia (NSIP) in SSc patients and usual interstitial pneumonia (UIP) in IPF patients. We used immunohistochemistry and histomorphometry to evaluate the expression of COX-1 and COX-2 in alveolar septa, vessels, and bronchioles. We then correlated that expression with pulmonary function test results and evaluated its impact on patient survival. The expression of COX-1 and COX-2 in alveolar septa was significantly higher in IPF-UIP and SSc-NSIP lung tissue than in the control tissue. No difference was found between IPF-UIP and SSc-NSIP tissue regarding COX-1 and COX-2 expression. Multivariate analysis based...

To determine the nature of hyaline membranes in different manifestations of diffuse alveolar damage, [pulmonary and extrapulmonary acute respiratory distress syndrome], and idiopathic [acute interstitial pneumonia]. Pulmonary specimens were obtained from 17 patients with acute respiratory distress syndrome and 9 patients with acute interstitial pneumonia. They were separated into 3 different groups: (a) pulmonary diffuse alveolar damage (pDAD) (n = 8), consisting only of pneumonia cases; (b) extrapulmonary diffuse alveolar damage (expDAI) (n = 9), consisting of sepsis and septic shock cases; and (c) idiopathic diffuse alveolar damage (iDAD) (n = 9), consisting of idiopathic cases (acute interstitial pneumonia). Hyaline membranes, the hallmark of the diffuse alveolar damage histological pattern, were examined using various kinds of antibodies. The antibodies used were against surfactant apoprotein-A (SP-A), cytokeratin 7 (CK7), cytokeratin 8 (CK8), alpha smooth muscle actin (alpha-SMA), cytokeratin AE1/AE3 (AE1/AE3), and factor VIII-related antigen (factor VIII). Pulmonary diffuse alveolar damage showed the largest quantity of hyaline membranes (12.65% +/- 3.24%), while extrapulmonary diffuse alveolar damage (9.52% +/- 3.64%) and idiopathic diffuse alveolar damage (7.34% +/- 2.11%) showed intermediate and lower amounts, respectively, with the difference being statistically significant between pulmonary and idiopathic diffuse alveolar damage (P < 0.05). No significant difference was found for hyaline membranes Sp-A immunostaining among pulmonary (15.36% +/- 3.12%), extrapulmonary (16.12% +/- 4.58%), and idiopathic (13.74 +/- 4.20%) diffuse alveolar damage groups. Regarding factor VIII, we found that idiopathic diffuse alveolar damage presented larger amounts of immunostained hyaline membranes (14.12% +/- 6.25%) than extrapulmonary diffuse alveolar damage (3.93% +/- 2.86%), with this difference being statistically significant (P < 0.001). Equally significant was the difference for progressive decrease of cytokeratin AE1/AE3 immunostaining in hyaline membranes present in the extrapulmonary diffuse alveolar damage (5.42% +/- 2.80%) and idiopathic diffuse alveolar damage (0.47% +/- 0.81%) groups (P < 0.001). None of the groups stained for cytokeratin CK-7, CK-8, vimentin, or a anti-smooth muscle actin. This study showed that only the epithelial/endothelial components (SP-A, factor VIII, and AE1/AE3) of the alveolar/capillary barrier are present in hyaline membranes formation in the 3 groups of patients with diffuse alveolar damage. The significant difference in the expression of factor VIII-related antigen and cytokeratin AE1/AE3 in the expDA versus iDAD groups as well as the significant difference in the amount of hyaline membranes present in the pDAD versus iDAD groups are suggestive of a local and specific lesion with different pathways (direct, indirect, or idiopathic), depending on the type of diffuse alveolar damage.

To investigate the effect of cilostazol, in kidney and skeletal muscle of rats submitted to acute ischemia and reperfusion. Fourty three animals were randomized and divided into two groups. Group I received a solution of cilostazol (10 mg/Kg) and group II received saline solution 0.9% (SS) by orogastric tube after ligature of the abdominal aorta. After four hours of ischemia the animals were divided into four subgroups: group IA (Cilostazol): two hours of reperfusion. Group IIA (SS): two hours of reperfusion. Group IB (Cilostazol): six hours of reperfusion. Group IIB (SS) six hours of reperfusion. After reperfusion, a left nephrectomy was performed and removal of the muscles of the hind limb. The histological parameters were studied. In kidney cylinders of myoglobin, vacuolar degeneration and acute tubular necrosis. In muscle interstitial edema, inflammatory infiltrate, hypereosinophilia fiber, cariopicnose and necrosis. Apoptosis was assessed by immunohistochemistry for cleaved caspase-3 and TUNEL. There was no statistically significant difference between groups. Cilostazol had no protective effect on the kidney and the skeletal striated muscle in rats submitted to acute ischemia and reperfusion in this model.

Fluoxetine treatment effects were determined by evaluating respiratory mechanics (elastance/resistance) and exhaled nitric oxide, as well as mononuclear and polymorphonuclear cell recruitment into the lungs, in an experimental guinea pig model. Guinea pigs were divided into four groups: Fl (fluoxetine only, n=7); Fl+Sw (fluoxetine and forced swimming, n=7); Ns+Sw (normal saline and forced swimming, n=8); and Ns (normal saline only, n=8). Treated animals received oral fluoxetine (10 mg/(kg day)) for 30 consecutive days. On day 31, all animals were anesthetized and mechanically ventilated so that respiratory system elastance and resistance, as well exhaled nitric oxide, could be determined. The lungs were then excised en bloc for histological and immunohistochemical evaluation. Forced swimming induced bronchodilation in untreated animals and bronchoconstriction in fluoxetine-treated animals. Fluoxetine treatment was also associated with mononuclear infiltration (predominantly into alveolar walls) and neutrophil recruitment. In addition, levels of exhaled nitric oxide, an inflammatory marker, were higher in fluoxetine-treated animals. Swimming-induced stress also amplified mononuclear cell recruitment to the lungs. These results show that, in this experimental model, fluoxetine treatment reproduces the pathology of chronic interstitial pneumonia in humans.

Organizing pneumonia (OP) is an inflammatory lung disease characterized histologically by intraluminal plugs involving alveolar ducts and alveoli. The aim was to examine extracellular matrix repair and remodelling in 12 cases of idiopathic OP and compare these with 11 cases of secondary OP. Collagen/elastic fibre density, myofibroblast proliferation, microvascular density and endothelial activity in the intraluminal plugs were evaluated by histochemistry, immunohistochemistry and morphometry. The density of the collagen system fibres was greater in plugs of idiopathic OP when compared with secondary OP (P < 0.001). Quantification of myofibroblastic cells confirmed differences observed in patterns of immunoexpression; when compared with secondary OP, idiopathic OP contained fewer myofibroblastic cells in intraluminal plugs (P = 0.01). Microvascular density (CD34) and endothelial activity (vascular cell adhesion molecule-1 and E-selectin) were significantly greater in secondary OP (P < 0.05). Idiopathic and secondary OP show significant variation in morphological features that may represent different responses to injury. Increased collagen synthesis, low myofibroblast proliferation, poor microvascularization and minimal endothelial activity found in idiopathic OP may be more of a remodelling process than secondary OP repair.

Bronchoalveolar lavage (BAL) is an established diagnostic tool in diffuse parenchyma lung disease. The objective of the present study was designed to investigate whether immunophenotyping affects BAL results and improves diagnostic accuracy. BAL from 61 patients was included in the study. The patients were also submitted to transbronchial biopsy, with a final diagnosis of granulomatous disease [tuberculosis (TB), n = 20; sarcoidosis (SARC), n = 3; and hypersensitivity pneumonitis (HP), n = 4]; idiopathic interstitial pneumonias (IIPs) [idiopathic pulmonary fibrosis (IPF), n = 9; organizing pneumonia (OP), n = 17]; and lung cancer (LC), n = 8. Immunohistochemistry and histomorphometry were used to identify and quantify type 1 and type 2 alveolar epithelial cells, macrophages, CD3+T-cells, CD4+T-cells, CD8+T-cells, and CD20+B-cells in BAL. These markers were correlated with a database and pulmonary function tests. The cellular, inflammatory, and immune components of BAL varied among the diagnostic groups and were negatively correlated with age and smoking history. An increased quantity of lymphocyte surface markers CD3 (P < 0.05) and CD20 (P = 0.01) was seen in IIPs. Patients with a pattern of OP had a higher proportion of type 2 alveolar epithelial cells; patients with SARC had a higher density of CD20+B-cells and CD4+T-helper cells; and patients with HP had a higher proportion of CD8+T-cytotoxic cells. A positive association was found between the density of type I alveolar epithelial cells and forced vital capacity. The immunophenotyping affects the cellular, inflammatory, or immune constituents of BAL and improved the diagnostic accuracy in diffuse parenchymal lung disease.

The prognostic relevance of different molecular markers in lung cancer is a crucial issue still worth investigating, and the specimens collected and analyzed represent a valuable source of material. Cyclin-D1, c-erbB-2 and vascular endothelial growth factor (VEGF) have shown to be promising as prognosticators in human cancer. In this study, we sought to examine the importance of Cyclin-D1, c-erbB-2 and VEGF, and to study the quantitative relationship among these factors and disease progression in metastases vs corresponding primary cancer, and metastatic vs non metastatic cancers. We used immunohistochemistry and morphometric analysis to evaluate the amount of tumour staining for Cyclin-D1, c-erbB-2 and VEGF in 52 patients with surgically excised adenocarcinoma of the lung, and the outcome for our study was survival time until death from hematogenic metastases. Metastasis presented lower c-erbB-2 expression than corresponding primary cancers (p=0.02). Cyclin-D1 and VEGF expression w...

Hyperhidrosis (HH) is a disease whose physiopathology remains poorly understood and that adverserly affects quality of life. There are no morphological studies that include an adequate control group that allows for comparison of the ganglion of HH to those of normal individuals .The purpose of study was analyze morphological and morphometric characteristics of the ganglion from patients with hyperhidrosis and normal individuals (organ donators). This was a transversal study. The sympathetic thoracic ganglia were obtained from two groups of patients.Group.PH (Palmar Hyperhidrosis), 40 patients with palmar HH submitted to surgery by video-assisted thoracoscopic (VATS) and Group C (control group), 14 deceased individuals (control group of organ donators) without any history of HH. The third left sympathetic thoracic ganglion was resected in all patients. We observed higher number of cells in the PH group than in Control group (14.25 + 3.81 versus 10.65 + 4.93),with p = 0,007 ; the mean...