Cecília Farhat

Prognostic Values of Stromal Proportion and PCNA, Ki-67, and p53 Proteins in Patients with Resected Adenocarcinoma of the Lung

Data from 64 patients who underwent surgical resection of lung adenocarcinomas were studied to identify clinicopathologic markers that might provide prognostic information on the clinical behavior of this neoplasia. Patient staging was performed in accordance with the tumor-node-metastasis system as follows: Stage I (n = 29), Stage II (n = 11), Stage IIIA (n = 21), and Stage IIIB (n = 3). Overall follow-up time corresponded to the follow-up time for patients who were alive and to the survival time for patients who had died, all of them expressed in months. Data included age, staging, histologic type, morphometric assessment of histologic features related to tumor (stroma and vascularization), and immunohistochemical detection of proliferation cell markers (Ki-67 protein and proliferating cell nuclear antigen) and p53 protein. The morphometric assessment was made by the point-counting procedure. Data analysis included Life Tables for Survival and Cox Regression models. Overall follow-up analysis showed that significant univariate predictors (P <.05) were T stage; N stage; tumor stromal proportion; and immunohistochemical indexes of proliferating cell nuclear antigen, Ki-67, and p53 proteins. Variables that presented independent predictive value for overall follow-up with the multivariate model (P <.05) were sex, T stage, N stage, tumor stromal proportion, and immunohistochemical detection of p53 protein. We conclude that tumor stromal proportion and immunohistochemical detection of p53 protein, controlled for sex, T stage, and N stage, may be of critical value in the evaluation of recurrence of lung adenocarcinoma, serving as indicators for a more accurate prognosis.

Protective effects of ascorbic acid pretreatment in a rat model of intestinal ischemia-reperfusion injury: A histomorphometric study

BACKGROUND Ascorbic acid has shown promise in attenuation of intestinal ischemia-reperfusion (I/R) injury. The aim of this study was to determine the protective effects of ascorbic acid on intestinal morphology during IR injury in rats. MATERIALS AND METHODS We examined morphological changes in the small intestine of Wistar rats after (i) 40 minutes of ischemia (I), (ii) ischemia followed by 30 min of reperfusion (IR), (iii) ischemia with ascorbic acid (IA), (iv) ischemia followed by reperfusion and ascorbic acid (IRA) and (v) in a sham group (S). We used morphometry to evaluate the amount of villous architecture, crypts, necrosis, hemorrhagic infarcts and inflammatory cells at the mesenteric and antimesenteric borders of the small intestine. RESULTS Ascorbic acid caused a significant reduction of antimesenteric villous hemorrhagic infarction (p<0.05) of the small intestine after ischemia followed by reperfusion as well as villous necrosis reduction at both borders after ischemia (p<0.05). The lesions found in the small intestine were more prominent along the antimesenteric margin. CONCLUSIONS Ascorbic acid pretreatment has a protective effect against the intestinal morphological lesions induced by ischemia-reperfusion injury in rats.

Semiquantitative assessment of surgical lung biopsy: predictive value and impact on survival of patients with diffuse pulmonary infiltrate

PURPOSE Surgical lung biopsy has been studied in distinct populations, mostly going beyond clinical issues to impinge upon routine histopathological diagnostic information in diffuse infiltrates; however, detailed tissue analyses have rarely been performed. The present study was designed to investigate the prognostic contribution provided by detailed tissue analysis in diffuse infiltrates. METHODS Medical records and surgical lung biopsies from the period of 1982 to 2003 of 63 patients older than 18 years with diffuse infiltrates were retrospectively examined. Lung parenchyma was histologically divided into 4 anatomical compartments: interstitium, airways, vessels, and alveolar spaces. Histological changes throughout these anatomical compartments were then evaluated according to their acute or chronic evolutional character. A semiquantitative scoring system was applied to histologic findings to evaluate the intensity and extent of the pathological process. We applied logistic regression to predict the risk of death associated with acute and chronic histological changes and to estimate the odds ratios for each of the independent variables in the model. RESULTS Impact on survival was found for male gender (P = 0.03), presence of diffuse alveolar damage (P = 0.001), and chronic histological changes (P = 0.0004) on biopsy. Thus, being male was associated with a slightly lower risk (O.R. = 0.18; P=0.03) of dying than being female. Death risk was increased 17 times in the presence of acute histological changes such as diffuse alveolar damage and 2.5 times in the presence of chronic histological changes. CONCLUSION Detailed analysis of histological specimens can provide more than a nosological diagnosis: this approach can provide valuable information concerning prognosis.

Demographic, etiological, and histological pulmonary analysis of patients with acute respiratory failure: a study of 19 years of autopsies

INTRODUCTION: Acute respiratory failure has been one of the most important causes of death in intensive care units, and certain aspects of its pulmonary pathology are currently unknown. OBJECTIVES: The objective was to describe the demographic data, etiology, and pulmonary histopathological findings of different diseases in the autopsies of patients with acute respiratory failure. METHOD: Autopsies of 4,710 patients with acute respiratory failure from 1990 to 2008 were reviewed, and the following data were obtained: age, sex, and major associated diseases. The pulmonary histopathology was categorized as diffuse alveolar damage, pulmonary edema, alveolar hemorrhage, and lymphoplasmacytic interstitial pneumonia. The odds ratio of the concordance between the major associated diseases and specific autopsy findings was calculated using logistic regression. RESULTS: Bacterial bronchopneumonia was present in 33.9% of the cases and cancer in 28.1%. The pulmonary histopathology showed diffuse alveolar damage in 40.7% (1,917) of the cases. A multivariate analysis showed a significant and powerful association between diffuse alveolar damage and bronchopneumonia, HIV/AIDS, sepsis, and septic shock, between liver cirrhosis and pulmonary embolism, between pulmonary edema and acute myocardial infarction, between dilated cardiomyopathy and cancer, between alveolar hemorrhage and bronchopneumonia and pulmonary embolism, and between lymphoplasmacytic interstitial pneumonia and HIV/AIDS and liver cirrhosis. CONCLUSIONS: Bronchopneumonia was the most common diagnosis in these cases. The most prevalent pulmonary histopathological pattern was diffuse alveolar damage, which was associated with different inflammatory conditions. Further studies are necessary to elucidate the complete pathophysiological mechanisms involved with each disease and the development of acute respiratory failure.

Autopsy-proven causes of death in lungs of patients immunocompromised by secondary interstitial pneumonia

PURPOSE To present the more frequent associations found in autopsies of immunocompromised patients who developed secondary interstitial pneumonia as well as the risk of death (odds ratio) in having specific secondary interstitial pneumonia according to the cause of immunocompromise. METHOD From January 1994 to March 2004, 17,000 autopsies were performed at Hospital das Clínicas, São Paulo University Medical School. After examining the pathology report review, we selected 558 of these autopsies (3.28%) from patients aged 15 years or more with primary underlying diseases who developed radiologically diffuse infiltrates of the lung during their hospital course and died after secondary interstitial pneumonia (bronchopneumonia, lobar pneumonia, interstitial pneumonia, diffuse alveolar damage, pulmonary recurrence of underlying disease, drug-induced lung disease, cardiogenic pulmonary edema, or pulmonary embolism). Histology slides were reviewed by experienced pathologists to confirm or not the presence of secondary interstitial pneumonia. Statistical analysis included the Fisher exact test to verify any association between histopathology and the cause of immunocompromise; a logistic regression was used to predict the risk of death for specific histological findings for each of the independent variables in the model. RESULTS Secondary interstitial pneumonia was histologically represented by diffuse interstitial pneumonitis ranging from mild nonspecific findings (n = 213) to a pattern of diffuse alveolar damage (n = 273). The principal causes of immunocompromise in patients with diffuse alveolar damage were sepsis (136 cases), neoplasia (113 cases), diabetes mellitus (37 cases), and transplantation (48 cases). A high risk of death by pulmonary edema was found for patients with carcinoma of colon. Similarly, in patients with lung cancer or cachexia, A high risk of death by bronchopneumonia (OR = 3.6; OR = 2.6, respectively) was found. Pulmonary thromboembolism was associated with an appreciable risk of death (OR = 2.4) in patients with arterial hypertension. The risk of death was also high in patients presenting hepatic cancer (OR = 2.5) or steroid therapy (OR = 2.4) who developed pulmonary hemorrhage as the histological pattern of secondary interstitial pneumonia . The risk of death by lung metastasis was also elevated (OR = 1.6) for patients that were immunosuppressed after radiotherapy. CONCLUSION Patients with secondary immunosuppression who developed secondary interstitial pneumonia during treatment in hospital should be evaluated to avoid death by diffuse alveolar damage, pulmonary edema, bronchopneumonia, lung hemorrhage, pulmonary thromboembolism, or lung metastasis. The high-risk patients are those immunosuppressed by hematologic disease; those under steroid treatment; or those with colon or hepatic carcinoma, cachexia, or arterial hypertension.

Autopsy-Proven Determinants of Immediate Fire Death in Lungs

In immediate fire deaths, pulmonary injury may be the main source of mortality, being important to document the histologic findings for the purpose of excluding other modes of death, such as from asphyxia with no gross findings. In this context, a group of morphologic determinants have been targeted with useful makers of pulmonary injury. To facilitate the determination of whether an individual was deceased before the start of a fire and validate the importance of parenchymal alterations in pulmonary injury in fire deaths, we studied lungs in victims of fire (N = 28) and suffocation (N = 40), creating a mathematical model using cluster analysis. For this purpose, a semiquantitative analysis of the distal parenchyma was performed to evaluate the amount of bronchiolar dilatation, overinsufflation (ductal and alveolar), collapse (ductal and alveolar), passive congestion, alveolar edema, and hemorrhage (interstitial and alveolar). These 7 histologic determinants were useful to discriminate fire (bronchiolar dilatation, ductal overinsuflation, alveolar overinsuflation, alveolar hemorrhage) from suffocation lung injuries (alveolar collapse, congestion, and edema). We conclude that these determinants should be included in the routine of forensic pathology.

Usefulness of complementary next-generation sequencing and quantitative immunohistochemistry panels for predicting brain metastases and selecting a treatment outcomes of non–small cell lung cancer

To demonstrate the usefulness of complementary next-generation sequencing (NGS) and immunohistochemistry (IHC) counting, we analyzed 196 patients with non-small cell lung cancer who underwent surgical resection and adjuvant chemotherapy. Formalin-fixed, paraffin-embedded samples of adenocarcinoma (ADC), squamous cell carcinoma, and large cell carcinoma were used to prepare tissue microarrays and were examined by protein H-score IHC image analysis and NGS for oncogenes and proto-oncogenes and genes of tumor suppressors, immune checkpoints, epithelial-mesenchymal transition factors, tyrosine kinase receptors, and vascular endothelial growth factors. In patients with brain metastases, primary tumors expressed lower PIK3CA protein levels. Overexpression of p53 and a higher PD-L1 protein H-score were detected in patients who underwent surgical treatment followed by chemotherapy as compared with those who underwent only surgical treatment The absence of brain metastases was associated with wild-type sequences of genes EGFR, CD267, CTLA-4, and ZEB1. The combination of protein overexpression according to IHC and mutation according to NGS was rare (ie, represented by a very low percentage of concordant cases), except for p53 and vascular endothelial growth factor. Our data suggest that protein levels detected by IHC may be a useful complementary tool when mutations are not detected by NGS and also support the idea to expand this approach beyond ADC to include squamous cell carcinoma and even large cell carcinoma, particularly for patients with unusual clinical characteristics. Conversely, well-pronounced immunogenotypic features seemed to predict the clinical outcome after univariate and multivariate analyses. Patients with a solid ADC subtype and mutated genes EGFR, CTLA4, PDCD1LG2, or ZEB1 complemented with PD-L1 or p53 protein lower expression that only underwent surgical treatment who develop brain metastases may have the worst prognosis.

Histomorphometric Evaluation of the Ki-67 Proliferation Rate and CD34 Microvascular and D2-40 Lymphovascular Densities Drives the Pulmonary Typical Carcinoid Outcome

Ki-67 has shown promise as a prognostic factor in pulmonary carcinoids. In this study, we sought to validate the importance of Ki-67 and study the relationships between Ki-67 and other stromal biomarkers of vascular density. We examined Ki-67, CD34, and D2-40 in tumor tissues from 128 patients with surgically excised typical carcinoid of the lung. We used immunohistochemistry and morphometry to evaluate the amount of tumor staining for cellular proliferation (Ki-67), microvascular density (CD34-MVD), and D2-40 lymphovascular density. The main outcome was overall survival, considered as life expectancy until death from metastasis. Specimens from patients with central tumors showed high CD34-MVD (P = .01), which was also significantly associated with a compromised surgical margin, lymph node metastasis, and clinical stage Ib. Equally significant was high D2-40 lymphovascular density in central specimens with a compromised surgical margin and lymph node metastasis. A high Ki-67 proliferation rate was significantly associated with tumors from patients with clinical stage IIb, IIIa, and IV disease. Multivariate Cox model analysis demonstrated that tumor location and stage, surgical margin, tumor size, and N stage were significantly related to survival time (P < .05). Quantitative staining of the tumor for Ki-67 and CD34-MVD served as prognostic factors (P < .05), which were more relevant than the surgical and pathological stage. Ki-67 greater than 5% and CD34-MVD greater than 7% staining comprise a subset of patients with higher death hazard; this outcome may harbor evidence for further prospective studies of target therapy after surgical resection.

Breve reflexão sobre a importância do método científico

Este texto faz uma reflexao sobre o Metodo Cientifico como a maneira segura e viavel para se chegar a uma explicacao acerca de um objeto ou fenomeno. Pelo metodo ha como conhecer e sistematizar os objetos ou fenomenos, pois possibilita acrescer, e tambem abre caminhos para questionar seus proprios achados e refutar conhecimentos ja adquiridos.