En Bloc Resection of Bladder Tumors (ERBT) using different lasers - Hybrid and Holmium Laser

ABSTRACT Introduction: The En-bloc Resection of Bladder Tumors (ERBT) is a method that offers more benefits compared to the traditional Transurethral Resection of Bladder Tumor (TURBT) (1, 2). Recent studies have shown that ERBT offers better pathological analysis and oncological outcomes (3-6). Thulium and holmium are the most frequently used lasers for this procedure, with the hybrid laser being a new addition that combines thulium and diode to improve hemostatic properties (5, 7-9). Objective: This report aims to discuss the use of two types of lasers, hybrid and holmium, for ERBT. Material and Methods: Two case studies were conducted. The first case featured a 68-year-old male with two tumors measuring 1.5cm and 2cm. The hybrid laser was used for the procedure. The second case involved a 70-year-old female with a 5cm tumor on the posterior bladder wall, and holmium laser was used with morcellation of the tumor. The quality of histopathological analysis was evaluated. The perioperative data and the entire procedure of the two cases were documented in a step-by-step video. Results: Both lasers demonstrated excellent results without technical difficulties. There was no bleeding, and both patients were discharged with one day of hospitalization. The detrusor muscle was present without artifacts, and the morcellation did not affect the analysis. The first case showed a pT1G3, and the second case showed a pT2 urothelial carcinoma. The hybrid laser exhibited superior hemostatic capacity compared to the holmium laser. Conclusion: ERBT can use hybrid or holmium lasers without affecting histopathological analysis, even with morcellation.

Can we use Ki67 expression to predict prostate cancer aggressiveness? / Podemos usar a expressão de Ki67 para prever a agressividade do câncer de próstata?

ABSTRACT Introduction: specialists have an urge for biomarkers that can discriminate indolent prostate cancer from aggressive tumors. Ki67 is a proliferation marker, and its expression is associated with the aggressiveness of several cancers. Objective: analyze the expression of Ki67 in prostate cancer samples correlating with the aggressiveness of the disease. Methods: Ki67 mRNA levels were determined utilizing data from a TCGA cohort (Tumor(n)=492 and control(n)=52). The protein expression was determined on 94 biopsies from patients by immunohistochemical assay. Results: in mRNA, the Ki67 upregulation is associated with cancer tissue (p<0.0001) and worst disease-free survival (p=0.035). The protein upregulation is associated with increase of the ISUP score (p<0.0001), cancer stage (p=0.05), biochemical recurrence (p=0.0006) and metastasis (p<0.0001). We also show a positive correlation between Ki67 expression and ISUP score (r=0.5112, p<0.0001) and disease risk stratification (r=0.3388, p=0.0009). Ki67 expression is a factor independently associated with biochemical recurrence (p=0.002) and metastasis (p<0.0001). Finally, the patients with high Ki67expression shows better survival regarding biochemical recurrence (p=0.008) and metastasis (p=0.056). Patients with high Ki67 expression are 2.62 times more likely to develop biochemical recurrence (p=0.036). Conclusion: Ki67 upregulation is associated with prostate cancer aggressiveness.

RESUMO Introdução: especialistas precisam biomarcadores que podem discriminar o câncer de próstata indolente de tumores agressivos. Ki67 é um marcador de proliferação, e sua expressão está associada à agressividade de vários tumores. Objetivo: analisar a expressão do Ki67 em amostras de câncer de próstata correlacionando com a agressividade da doença. Métodos: os níveis de mRNA de Ki67 foram determinados utilizando dados de uma coorte de TCGA (Tumor(n)=492 e controle(n)=52). A expressão da proteína foi determinada em 94 biópsias de pacientes por ensaio imuno-histoquímica. Resultados: no mRNA, a superexpressão Ki67 está associada ao tecido canceroso (p<0,0001) e à pior sobrevida livre de doença (p=0,035). A superexpressão proteica está associada ao aumento do escore ISUP (p<0,0001), estágio de câncer (p=0,05), recorrência bioquímica (p=0,0006) e metástase (p<0,0001). Também mostramos uma correlação positiva entre a expressão Ki67 e o escore ISUP (r=0,5112, p<0,0001) e a estratificação de risco de doença (r=0,3388, p=0,0009). A expressão Ki67 é um fator independentemente associado à recorrência bioquímica (p=0,002) e metástase (p<0,0001). Finalmente, os pacientes com alta expressão de Ki67 expression mostram melhor sobrevivência em relação à recorrência bioquímica (p=0,008) e metástase (p=0,056). Os pacientes com alta expressão de Ki67 são 2,62 vezes mais propensos a desenvolver recorrência bioquímica (p=0,036). Conclusão: a superexpressão Ki67 está associada à agressividade do câncer de próstata.

Detecting and grading prostate cancer in radical prostatectomy specimens through deep learning techniques

OBJECTIVES: This study aims to evaluate the ability of deep learning algorithms to detect and grade prostate cancer (PCa) in radical prostatectomy specimens. METHODS: We selected 12 whole-slide images of radical prostatectomy specimens. These images were divided into patches, and then, analyzed and annotated. The annotated areas were categorized as follows: stroma, normal glands, and Gleason patterns 3, 4, and 5. Two analyses were performed: i) a categorical image classification method that labels each image as benign or as Gleason 3, Gleason 4, or Gleason 5, and ii) a scanning method in which distinct areas representative of benign and different Gleason patterns are delineated and labeled separately by a pathologist. The Inception v3 Convolutional Neural Network architecture was used in categorical model training, and a Mask Region-based Convolutional Neural Network was used to train the scanning method. After training, we selected three new whole-slide images that were not used during the training to evaluate the model as our test dataset. The analysis results of the images using deep learning algorithms were compared with those obtained by the pathologists. RESULTS: In the categorical classification method, the trained model obtained a validation accuracy of 94.1% during training; however, the concordance with our expert uropathologists in the test dataset was only 44%. With the image-scanning method, our model demonstrated a validation accuracy of 91.2%. When the test images were used, the concordance between the deep learning method and uropathologists was 89%. CONCLUSION: Deep learning algorithms have a high potential for use in the diagnosis and grading of PCa. Scanning methods are likely to be superior to simple classification methods.

Study of kidney morphologic and structural changes related to different ischemia times and types of clamping of the renal vascular pedicle

ABSTRACT Purpose This study aimed to study morphological and renal structural changes in relation to different ischemic times and types of renal vascular pedicle clamping. Methods Sixteen pigs were divided into two groups (n = 8): Group AV - unilateral clamping of the renal artery and vein and Group A - unilateral clamping of the renal artery only, both with the contralateral kidney used as control. Serial biopsies were performed at 0, 10, 20, 30, 40, 50, 60, 70, 80, and 90 minutes after clamping. Results there is a correlation between the occurrence of renal damage as a function of time (p <0.001), with a higher frequency of Group A lesions for cellular alterations (vascular congestion and edema, interstitial inflammatory infiltrate, interstitial hemorrhage and cell degeneration), with the exception of in the formation of pigmented cylinders that were evidenced only in the AV Group. Conclusion the number of lesions derived from ischemia is associated with the duration of the insult, there is a significant difference between the types of clamping, and the AV Group presented a lower frequency of injuries than Group A. The safety time found for Group A was 10 minutes and for Group AV 20 minutes.

O uso de microRNA para tratamento do câncer de próstata: estudos in vitro e in vivo / The use of microRNA for the treatment of prostate cancer: in vitro and in vivo studies

O câncer de próstata (CaP) é o tumor mais comum do homem nos países ocidentais e a segunda causa de óbito por câncer em homens nos EUA, Europa e Brasil. O câncer localizado tem sobrevida câncer especifica elevada quando tratado adequadamente, porém a doença metastática ainda apresenta tratamentos pouco eficientes com sobrevida global de 28%. Os microRNAs (miRNAs) são um grupo de moléculas pequenas de RNA que contém entre 19 a 25 nucleotídeos não codificantes de proteína, com ação fundamental na regulação da expressão gênica. Eles estão envolvidos em processos essenciais nas células normais e neoplásicas como ciclo celular, proliferação, apoptose, metabolismo energético, invasão e metastatização. Objetivos: Realizar estudos in vitro e in vivo usando miRNA em um modelo de câncer de próstata metastático inédito no nosso meio com intuito de analisar o seu potencial como agente terapêutico dessa neoplasia. Métodos: Nos estudos in vitro, três linhagens celulares foram utilizadas (PC3, DU145 e LNCaP). Essas linhagens foram transfectadas com os miRNAs 100, 145 e 373 e seus respectivos antiMiRs utilizando-se lipofectamina. Analisamos a expressão dos genes alvo mTOR, SMARCA5, KRAS, CMYC, MMP9, CD44 por PCR quantitativo em tempo real (qRT-PCR). Foram realizados também estudos de apoptose, ciclo celular e ploidia utilizando o citômetro de fluxo. Alterações no potencial de invasão foram avaliadas pela técnica do matrigel. O modelo in vivo pré-clínico foi desenvolvido pela injeção intra-cardíaca da linhagem PC-3M-Luc-C6 em camundongos NUDE com 9 semanas. O crescimento tumoral foi avaliado com o sistema de bioluminescência in vivo. Após o pleno estabelecimento das metástases no dia 21, os animais foram tratados com três injeções na veia da cauda contendo o miRNA conjugado com o atelocolágeno. Os animais foram sacrificados e no dia 48 para análise dos tecidos. Resultados: miR-100 aumenta a apoptose na LNCaP, e reduz a apoptose na DU145. Na linhagem DU145...

Prostate cancer (PCa) is the most common neoplasia of man in Western countries and the second cause of death by cancer in men in the US, Europe and Brazil. The localized cancer has high cancer-specific survival when treated properly, however metastatic disease still presents low effective treatments with 28% of global survival. microRNAs (miRNAs) are a group of small RNA molecules containing from 19 to 25 nucleotides of noncoding protein with fundamental action in the regulation of gene expression. They are involved in key processes in normal and neoplastic cells as cell cycle, proliferation, apoptosis, energy metabolism, invasion and metastasis. Objectives: To carry out studies in vitro and in vivo using miRNA in a novel model of metastatic prostate cancer in our country in order to evaluate its potential as a therapeutic agent of this neoplasia. Methods: In the in vitro studies, three cell lines were used (PC3, DU145 and LNCaP). These cell lines were transfected with miRNAs 100, 145 and 373 and their antiMiRs using lipofectamine. We analyzed the gene expression of mTOR, SMARCA5, KRAS, CMYC, MMP9, CD44 by real-time polymerase chain reaction (qRT-PCR). We also performed studies of apoptosis, cell cycle and ploidy using flow cytometer. Changes in the invasion potential were evaluated by the technique of matrigel. The pre-clinical model in vivo was developed by intracardiac injection of PC-3MLuc-C6 cell line in NUDE mice with 9 weeks. Tumor growth was evaluated with an in vivo image system (IVIS). After the full establishment of metastases on day 21, the animals were treated with three injections into the tail vein containing the miRNA plus atelocollagen. The animals were sacrificed on day 48 for tissues analysis. Results: MiR-100 increases apoptosis in LNCaP and reduces apoptosis in DU145. The anti-miR-100 increased apoptosis in 14% in PC3. In cell line DU145, miR-100 inhibited proliferation. In the analysis of gene expression, the miR-100...

Classificação molecular dos carcinomas de mama: uma visão contemporânea / Molecular classification of breast cancer: a contemporary view

RESUMO O câncer de mama é uma doença heterogênea com comportamentos diferentes. O progresso da biotecnologia permitiu sua classificação molecular por perfis de expressão gênica, a saber: luminal A, luminal B, superexpressor de HER-2, basaloide, ?normal like?, ?claudin-low? e molecular apócrino. As características biológicas e moleculares dos subtipos são apresentadas e discutidas, assim como sua importância prognóstica. Existe uma forte correlação entre classificação dos tumores por ?microarray? de DNA e reações imuno-histoquímicas, o que facilita seu uso na prática diária. Porém, um amplo espectro de neoplasias é incluído como triplo-negativo (com negatividade de receptores de estrogênio e progesterona e oncogene HER-2) e é possível discriminá-las em distintas formas genômicas.

Breast cancer is a heterogeneous disease with different evolutions. The progress of biotechnology allowed its molecular classification based in genetic expression profiles, as follows: luminal A, luminal B, HER-2 superexpressor, basal-like, normal-like, claudin-low and molecular apocrine. Biologic and molecular characteristics of the subtypes are presented, as well as their prognostic importance. There is strong correlation between the DNA microarray classification and immunohistochemistry, making easier ITS usage in the daily practice. There is a wide spectrum of triple-negative neoplasias (estrogen and progesterone negative receptors, and HER-2 oncogene negative) and it is possible to discriminate them in several genomic forms.

Loss of TIMP-1 immune expression and tumor recurrence in localized prostate cancer

Introduction and objective: Overexpression of MMPs has been related to biochemical recurrence after radical prostatectomy. TIMP1 and TIMP2 are controllers of MMPs and the aim of this study is to evaluate the expression levels of MMPs and their regulators using immunohistochemistry in tissue microarray of localized prostate cancer (PC). Materials and Methods: Immune-expression of MMP-9, MMP-2, TIMP1, TIMP-2, MMP-14 and IL8, were analyzed by immunohistochemistry in radical prostatectomy specimens of 40 patients with localized PC who underwent surgery between September 1997 and February 2000. Protein expression was considered as categorical variables, negative or positive. The results of the immune-expression were correlated to Gleason score (GS), pathological stage (TNM), pre-operatory PSA serum levels and biochemical recurrence in a mean follow up period of 92.5 months. Results: The loss of TIMP1 immune-expression was related to biochemical recurrence. When TIMP1 was negative, 56.3% patients recurred versus 22.2% of those whose TIMP1 was positive (p=0.042). MMP-9, MMP-2, IL8 and MMP-14 were positive in the majority of PC. TIMP-2 was negative in all cases. Conclusion: Negative immune-expression of TIMP1 is correlated with biochemical recurrence in patients with PC possibly by failing to control MMP-9, an important MMP related to cancer progression.

Evaluation of the metabolism of glycosaminoglycans in patients with interstitial cystis

Introduction: Painful bladder syndrome/interstitial cystitis (PBS/IC) pathogenesis is not fully known, but evidence shows that glycosaminoglycans (GAG) of bladder urothelium can participate in its genesis. The loss of these compounds facilitates the contact of urine compounds with deeper portions of bladder wall triggering an inflammatory process. We investigated GAG in urine and tissue of PBS/IC and pure stress urinary incontinence (SUI) patients to better understand its metabolism. Materials and Methods: Tissue and urine of 11 patients with PBS/IC according to NIDDK criteria were compared to 11 SUI patients. Tissue samples were analyzed by histological, immunohistochemistry and immunofluorescence methods. Statistical analysis were performed using t Student test and Anova, considering significant when p < 0.05. Results: PBS/IC patients had lower concentration of GAG in urine when compared to SUI (respectively 0.45 ± 0.11 x 0.62 ± 0.13 mg/mg creatinine, p < 0.05). However, there was no reduction of the content of GAG in the urothelium of both groups. Immunofluorescence showed that PBS/IC patients had a stronger staining of TGF-beta, decorin (a proteoglycan of chondroitin/dermatan sulfate), fibronectin and hyaluronic acid. Conclusion: the results suggest that GAG may be related to the ongoing process of inflammation and remodeling of the dysfunctional urothelium that is present in the PBS/IC. .

Immune expression of E-cadherin and α, β and γ-Catenin adhesion molecules and prognosis for upper urinary tract urothelial carcinomas

INTRODUCTION: Cell adhesion molecules (CAM) are required for maintaining a normal epithelial phenotype, and abnormalities in CAM expression have been related to cancer progression, including bladder urothelial carcinomas. There is only one study that correlates E-cadherin and α-, β- and γ-catenin expression with prognosis of upper tract urothelial carcinomas. Our aim is to study the pattern of immune expression of these CAMs in urothelial carcinomas from the renal pelvis and ureter in patients who have been treated surgically. Our goal is to correlate these expression levels and characteristics with well-known prognostic parameters for disease-free survival. MATERIALS AND METHODS: We evaluated specimens from 20 patients with urothelial carcinomas of the renal pelvis and ureter who were treated with nephroureterectomy or ureterectomy between June 1997 and January 2007. CAM expression was evaluated by immunohistochemistry in a tissue microarray and correlated with histopathological characteristics and patient outcomes after a mean follow-up of 55 months. RESULTS: We observed a relationship between E-cadherin expression and disease recurrence. Disease recurrence occurred in 87.5% of patients with strong E-cadherin expression. Only 50.0% of patients with moderate expression and 0% of patients with weak or no expression of E-cadherin had disease recurrence (p = 0.014). There was also a difference in disease-free survival. Patients with strong E-cadherin expression had a mean disease-free survival rate of 49.1 months, compared to 83.9 months for patients with moderate expression (p = 0.011). Additionally, an absence of α-catenin expression was associated with tumors that were larger than 3 cm (p = 0.003). CONCLUSIONS: We demonstrated for the first time that immune expression of E-cadherin is related to tumor recurrence and disease-free survival rates, and the absence of α-catenin expression is related to tumor size in upper tract urothelial carcinomas.

Tgf-β1 expression as a biomarker of poor prognosis in prostate cancer

OBJECTIVE: To evaluate the correlation between transforming growth factor beta (TGF-β1) expression and prognosis in prostate cancer. PATIENTS AND METHODS: TGF-β1 expression levels were analyzed using the quantitative real-time polymerase chain reaction to amplify RNA that had been isolated from fresh-frozen malignant and benign tissue specimens collected from 89 patients who had clinically localized prostate cancer and had been treated with radical prostatectomy. The control group consisted of li patients with benign prostate hyperplasia. The expression levels of TGF-β1 were compared between the groups in terms of Gleason scores, pathological staging, and prostate-specific antigen serum levels. RESULTS: In the majority of the tumor samples, TGF-β1 was underexpressed 67.0 percent of PCa patients. The same expression pattern was identified in benign tissues of patients with prostate cancer. Although most cases exhibited underexpression of TGF-β1, a higher expression level was found in patients with Gleason scores >7 when compared to patients with Gleason scores <7(p = 0.002). Among the 26 cases of TGF-β1 overexpression, 92.3 percent had poor prognostic features. CONCLUSIONS: TGF-β1 was underexpressed in prostate cancers; however, higher expression was observed in tumors with higher Gleason scores, which suggests that TGF-β1 expression may be a useful prognostic marker for prostate cancer. Further studies of clinical specimens are needed to clarify the role of TGF-β1 in prostate carcinogenesis.

Prostate cancer detection at rebiopsy after an initial benign diagnosis: results using sextant extended prostate biopsy

INTRODUCTION: Sextant prostate biopsy remains the standard technique for the detection of prostate cancer. It is well known that after a diagnosis of small acinar proliferation (ASAP) or high grade prostate intraepithelial neoplasia (HGPIN), the possibility of finding cancer is approximately 40 percent and 30 percent, respectively. OBJECTIVE: We aim to analyze follow-up biopsies on patients who initially received a benign diagnosis after exclusion of HGPIN and ASAP. METHODS: From July 2000 to December 2003, 1177 patients were submitted to sextant extended prostate biopsy in our hospital. The mean patient age was 65.5 years old, and the median number of fragments collected at biopsy was 13. HGPIN and ASAP were excluded from our study. We only considered patients who had a diagnosis of benign at the first biopsy and were subjected to rebiopsies up until May 2005 because of a maintained suspicion of cancer. RESULTS: Cancer was initially detected in 524 patients (44.5 percent), and the diagnosis was benign in 415 (35.3 percent). Rebiopsy was indicated for 76 of the latter patients (18.3 percent) because of a persistent suspicion of cancer. Eight cases of adenocarcinoma (10.5 percent) were detected, six (75 percent) at the first rebiopsy. Six patients were submitted to radical prostatectomy, and all tumors were considered clinically significant. CONCLUSION: Our data indicate that in extended prostate biopsy, the first biopsy detects more cancer, and the first, second, and third rebiopsies after an initial benign diagnosis succeed in finding cancer in 7.9 percent (6/55), 5.9 percent (1/15) and 20 percent (1/4) of patients, respectively.

Importância prognóstica da invasão neural no câncer colorretal: estudo imunoistoquímico com a proteína S-100 / Prognostic importance of neural invasion in colorectal cancer: an immunohistochemical study with the S-100 protein

Das variáveis anatomopatológicas relacionadas ao prognóstico de enfermos com câncer colorretal, a invasão neural ainda se encontra pouco estudada. OBJETIVO: Verificar se a invasão neural no câncer colorretal estádios B e C de Dukes pode ser considerada como fator prognóstico independente. MÉTODO: Foram estudados 97 doentes operados com intenção curativa e seguidos por período mínimo de cinco anos. Excluíram-se doentes que receberam tratamento adjuvante. Os espécimes cirúrgicos foram corados por hematoxilina-eosina e imunoistoquímica para pesquisa da proteína S-100, com o intuito de se comparar a fidedignidade das técnicas em detectar invasão neural, sendo analisadas comparativamente: acurácia, especificidade, sensibilidade e valores preditivos positivo e negativo. A comparação entre a incidência de invasão neural com relação à recidiva foi realizada, empregando-se o teste do qui-quadrado. A sobrevida e sobrevida livre de doença foram estudadas por análise univariada,. Estabeleceu-se nível de significância de 5 por cento (p ú 0,05) para todos os testes adotados. RESULTADOS: A técnica da HE apresentou fraca habilidade em detectar a invasão neural, não sendo adequada para esta análise em doentes portadores de câncer colorretal. As curvas de sobrevida e sobrevida livre de doença dos enfermos portadores de invasão neural, pesquisada por meio da imunocoloração para proteína S-100 são significativamente piores, identificando aquela característica histológica como valor prognóstico independente (p = 0,0003 e p = 0,0002, respectivamente). A ocorrência de recidiva tumoral foi significativamente maior nos doentes que apresentavam invasão neural (p = 0,0010). CONCLUSÃO: Os resultados do presente estudo permitem concluir que, nos doentes portadores de câncer colorretal, a detecção da invasão neural pela pesquisa imunoistoquímica da proteína S-100 demonstrou ser variável independente, acrescentando informações prognósticas adicionais nos doentes classificados nos estádios ...

Among the anatomopathological variables related to the prognosis for patients with colorectal cancer, neural invasion remains little studied. OBJECTIVE: To evaluate whether neural invasion in patients with colorectal cancer in Dukes stages B and C could be considered to be an independent prognostic factor, by means of univariate and multivariate analysis. METHODS: Ninety-seven patients who underwent operations with curative intent by the same surgical team were followed up for a minimum period of five years and were studied. Patients who received adjuvant treatment were excluded. The surgical specimens were stained with hematoxylin-eosin (HE) and immunohistochemical techniques for S-100 protein analysis, with the aim of comparing the two techniques for detecting neural invasion. Accuracy, specificity, sensitivity and positive and negative predictive values were analyzed for HE in relation to S-100 protein. Comparison between the incidence of neural invasion and tumor recurrence was made by using the chi-squared test. Survival and disease-free survival were studied by univariate analysis. A significance level of 5 percent (p ú 0.05) was established for all the tests adopted. RESULTS: The HE technique presented weak ability to detect neural invasion and was inadequate for this analysis in colorectal cancer patients. The survival and disease-free survival curves for patients with neural invasion, investigated by means of immunostaining for S-100 protein, were significantly worse, thus identifying this histological characteristic as having independent prognostic value (p = 0.0003 and p = 0.0002, respectively). There was significantly more tumor recurrence among patients who presented neural invasion (p = 0.0010). CONCLUSION: The results from the present study allow the conclusion that, among colorectal cancer patients, neural invasion was shown to be an independent variable that gave additional prognostic information regarding patients in stages B, C and C2 of...

Pure sarcomatous recurrence of clear cell renal carcinoma following radical nephrectomy and dendritic cell vaccination / Recorrência sarcomatosa pura após nefrectomia radical e vacina de células dendríticas no carcinoma renal de células claras

CONTEXT: Sarcomatous differentiation, which represents transformation to high-grade malignancy, can occur in all histogical types of renal malignancy. CASE REPORT: The authors report on the case of a 66-year-old woman with a right renal mass that was shown to be a clear cell carcinoma. She underwent radical nephrectomy and dendritic cell vaccination and, 3.5 years later, she developed retroperitoneal pure sarcomatous recurrence of the tumor. The authors speculate that the vaccination could have played some role in this differentiation or selection of the sarcomatous component of the primary tumor.

CONTEXTO: Diferenciação sarcomatosa, que representa evolução para malignidade de alto grau, pode ocorrer em todos os tipos histológicos de câncer renal. RELATO DE CASO: Os autores relatam o caso de uma mulher de 66 anos, com uma massa no rim esquerdo que se revelou um carcinoma de células renais. Após 3,5 anos da nefrectomia radical seguida de vacinação com células dendríticas, a paciente desenvolveu uma recorrência sarcomatosa pura no retroperitônio. Os autores especulam que a terapia com vacina de células dendríticas pode ter desempenhado algum papel na diferenciação ou seleção do componente sarcomatoso do tumor primário.

Helicobacter pylori and cagA gene detected by polymerase chain reaction in gastric biopsies: correlation with histological findings, proliferation and apoptosis

CONTEXTO E OBJETIVO: A virulência de Helicobacter pylori em doenças gastroduodenais está relacionada à presença de ilha de patogenicidade (cagPAI) que ocorre em algumas cepas. A infecção pelo cagPAI induz a secreção de IL-8, aumenta a proliferação epitelial, podendo ter um papel importante na carcinogênese. Nosso objetivo foi detectar HP e o gene cagA (marcador de cagPAI) pela técnica de PCR (polymerase chain reaction), correlacionando com os achados histológicos, de proliferação e apoptose. TIPO DE ESTUDO E LOCAL: Estudo retrospectivo, no Laboratório de Patologia Cirúrgica e Molecular do Hospital Sírio Libanês. MÉTODOS: DNA isolado de 164 biópsias gástricas foi submetido a PCR para detecção de HP. Os casos positivos foram submetidos a nova reação para identificação do gene cagA. Pela técnica de imunohistoquímica foi analisada a proliferação celular e, pela TUNEL, a apoptose. RESULTADOS: HP foi detectado em 67,7% dos pacientes. Houve correlação entre a presença do HP e o diagnóstico de gastrite moderada ou grave, úlcera e linfoma do tipo MALT. Houve correlação entre cagPAI+ e a doença gástrica grave, incluindo o câncer. O risco de úlcera, adenocarcinoma ou linfoma MALT para os portadores de cagA+ foi de 8,8. Infecção pelo cagPAI correlacionou-se com aumento na taxa de proliferação. O índice proliferação/apoptose foi significantemente maior para os pacientes cagPAI+. CONCLUSÕES: Uma desregulação do crescimento celular nos pacientes cagPAI+ foi demonstrada pela diferença do índice de proliferação, que acreditamos pode explicar o papel carcinogênico da bactéria.

Desdiferenciação do câncer da próstata após terapia antiandrogênica / Prostate cancer dedifferentiation following antiandrogen therapy: a morphological finding or an increased tumor aggressiveness?

OBJETIVO: O bloqueio androgênico neo-adjuvante em câncer da próstata produz involução do volume tumoral sem melhorar a evolução desses pacientes. Uma das explicações para esse fenômeno é a aquisição de comportamento mais agressivo pelas células tumorais remanescentes que, morfologicamente, apresentam aspecto mais indiferenciado após o bloqueio androgênico. Os objetivos do presente estudo foram avaliar a freqüência de desdiferenciação celular após tratamento antiandrogênico e definir se a neoplasia remanescente apresenta sinais de maior agressividade biológica. MÉTODOS: Trinta pacientes portadores de câncer da próstata localmente avançado foram submetidos a tratamento antiandrogênico neo-adjuvante por quatro meses, seguido de prostatectomia radical. Foram comparados os escores de Gleason da biópsia e do espécime cirúrgico. Ademais, mediu-se o índice de proliferação celular, determinado por imunohistoquímica para o PCNA, sendo considerados positivos os testes com reação nuclear intensa. A porcentagem de núcleos positivos, determinada em 500 células, foi confrontada com as diversas categorias do escore de Gleason do espécime cirúrgico. RESULTADOS: Em 11 espécimes cirúrgicos (37 por cento) o escore de Gleason foi igual ou menor que o encontrado na biópsia, enquanto em 19 (63 por cento) o escore cirúrgico foi maior que o da biópsia (p <0,05). A mediana de expressão do PCNA foi, respectivamente, de 4,5 por cento, 10 por cento, 12 por cento e 14 por cento para os escores de Gleason 2-4, 5-6, 7 e 8-10 (p> 0,05). A mediana dos índices de proliferação celular foi de 9 por cento para tumores confinados à glândula ou ao espécime e de 17 por cento para os extraprostáticos (p<0,05). CONCLUSÃO: Piora do escore de Gleason ocorreu em cerca de dois terços dos pacientes submetidos a tratamento hormonal anti-androgênico. Entretanto, os índices de proliferação celular, medidos pelo PCNA, foram iguais para espécimes com diferentes escores de Gleason. É provável que o bloqueio hormonal neo-adjuvante produza uma piora morfológica da neoplasia, sem, contudo, gerar clones celulares mais agressivos.

The role of HER2/neu, BCL2, p53 genes and proliferating cell nuclear protein as molecular prognostic parameters in localized prostate carcinoma

CONTEXTO: Câncer de próstata é a neoplasia geniturinária sólida mais freqüente no homem. Alguns genes foram identificados na iniciação e progressão do carcinoma de próstata. OBJETIVO: Estudar a expressão dos oncogenes HER2/neu e BCL2, do gene supressor p53, e da taxa de proliferação tumoral em 150 espécimes de prostatectomia radical, para definir o papel prognóstico desses parâmetros no câncer de próstata localizado. TIPO DE ESTUDO: Estudo prospectivo. LOCAL: Universidade Federal de São Paulo e Hospital Sírio Libanês, São Paulo. PARTICIPANTES: Cento e cinqüenta homens foram submetidos a prostatectomia radical entre agosto 1997 e agosto 1998, por câncer de próstata localizado. VARIAVEIS ESTUDADAS: Todos os espécimes foram submetidos à avaliação da porcentagem de volume tumoral, da extensão do tumor e da escala de Gleason. Imunohistoquímica foi realizada para determinar a expressão genética dos seguintes anticorpos: anti-HER2/neu, BCL2, p53, e proteína nuclear de proliferação celular. O teste qui-quadrado foi utilizado na correlação entre a expressão genética, a atividade proliferativa e as variáveis histológicas. RESULTADOS: Trinta por cento dos casos eram p53 positivos. Houve correlação positiva entre a expressão do p53 e o estágio tumoral. A porcentagem de expressão do p53 foi de 22.9% e de 42.6% para tumores pT2 e pT3, respectivamente, (p = 0,01). As expressões de HER2/neu, BCL2 e proteína nuclear de proliferação celular foram identificadas em 66%, 23% e 43% dos pacientes, respectivamente. Não houve correlação entre esses três parâmetros e o volume tumoral, a escala de Gleason ou o estágio da neoplasia. CONCLUSAO: Um terço dos adenocarcinomas prostáticos expressam a proteína p53, e essa característica está relacionada ao estágio tumoral. HER2/neu está freqüentemente expressado nos carcinomas de próstata, mas não existe correlação com os parâmetros histológicos. BCL2 e proteína nuclear de proliferação celular raramente estão expressados, não havendo correlação destes com as variáveis de prognóstico patológicos nessa neoplasia.

Primary lymphoma of the liver treated by extended hepatectomy and chemotherapy: a case report

Primary lymphoma of the liver is an extremely rare entity. A case of anaplastic large B-cell (both CD-20 and lambda positive) non-Hodgkin's lymphoma that was confined to the liver in a 33-year-old man is reported. The patient was treated with an extended right hepatectomy and combination chemotherapy: cyclophosphamide, adriamycin, vincristine, and prednisone. The patient was disease free 24 months after the procedure