The Brazilian national prospective active surveillance (AS) cohort of patients with low-risk prostate cancer in the public health system: vigiaSUS study protocol.

BACKGROUND: Prostate cancer exhibits a very diverse behaviour, with some patients dying from the disease and others never needing treatment. Active surveillance (AS) consists of periodic PSA assessment (prostate-specific antigen), DRE (digital rectal examination) and periodic prostate biopsies. According to the main guidelines, AS is the preferred strategy for low-risk patients, to avoid or delay definitive treatment. However, concerns remain regarding its applicability in certain patient subgroups, such as African American men, who were underrepresented in the main cohorts. Brazil has a very racially diverse population, with 56.1% self-reporting as brown or black. The aim of this study is to evaluate and validate the AS strategy in low-risk prostate cancer patients following an AS protocol in the Brazilian public health system. METHODS: This is a multicentre AS prospective cohort study that will include 200 patients from all regions of Brazil in the public health system. Patients with prostate adenocarcinoma and low-risk criteria, defined as clinical staging T1-T2a, Gleason score ≤ 6, and PSA < 10 ng/ml, will be enrolled. Archival prostate cancer tissue will be centrally reviewed. Patients enrolled in the study will follow the AS strategy, which involves PSA and physical examination every 6 months as well as multiparametric MRI (mpMRI) every two years and prostate biopsy at month 12 and then every two years. The primary objective is to evaluate the reclassification rate at 12 months, and secondary objectives include determining the treatment-free survival rate, metastasis-free survival, and specific and overall survival. Exploratory objectives include the evaluation of quality of life and anxiety, the impact of PTEN loss and the economic impact of AS on the Brazilian public health system. DISCUSSION: This is the first Brazilian prospective study of patients with low-risk prostate cancer under AS. To our knowledge, this is one of the largest AS study cohort with a majority of nonwhite patients. We believe that this study is an opportunity to better understand the outcomes of AS in populations underrepresented in studies. Based on these data, an AS national clinical guideline will be developed, which may have a beneficial impact on the quality of life of patients and on public health. TRIAL REGISTRATION: Clinicaltrials registration is NCT05343936.

The role of linear endosonography for the diagnosis of acute pancreatitis when other methods failed.

BACKGROUND AND STUDY AIMS: Acute pancreatitis has no obvious cause after clinical, laboratory and radiologic investigation in 10%-30% of patients, and the diagnosis of idiopathic pancreatitis is given. This study investigated the role of linear EUS for identification of possible causes for acute pancreatitis when other investigative methods failed. PATIENTS AND METHODS: Between June 2012 and March 2017, 35 patients [25 women; mean age: 51.9 + 17.8 years] with idiopathic acute pancreatitis underwent linear EUS for investigation. All of these cases were contacted for a follow-up telephone interview to compare the EUS findings with the final diagnosis and outcome. RESULTS: Pancreaticobiliary abnormalities were identified in 19 of 35 (54.3%) patients. Ten (28.6%) patients had microlithiasis or biliary sludge. Microlithiasis and choledocholithiasis were identified in 8 (22.8%) and a single (2.8%) patient, respectively. Two patients presented gallbladder biliary sludge, one of them with microlithiasis. Chronic pancreatitis was found on EUS in 6 (17.1%) patients, and pseudotumoral masses confirmed by EUS-FNA as autoimmune pancreatitis were detected in other 3 (8.6%) cases. Linear EUS was normal in 13 (37.1%) patients, and demonstrated findings of recent acute pancreatitis but no other etiological factor in 3 (8.6%) cases. After a mean follow-up of 33.3 months, no case with a normal EUS evaluation presented a new episode of pancreatitis, 1 of 9 cases with microlithiasis presented an episode of recurrent pancreatitis due to choledocolithiasis after cholecystectomy, and 3 of 9 cases with chronic pancreatitis presented recurrent episodes, including the 2 cases of autoimmune pancreatitis. CONCLUSIONS: Linear EUS provides diagnostic information in approximately a half of patients with idiopathic acute pancreatitis. Exclusion of pancreaticobiliary abnormalities on EUS has an important prognostic value for absence of new episodes of acute pancreatitis.

Differential diagnosis of mesenchymal neoplasms of the digestive tract by cell block and immunohistochemistry.

OBJECTIVES: To evaluate the diagnostic yield of the cell block (CB) technique with immunohistochemistry in patients with mesenchymal neoplasms of the gastrointestinal tract collected by endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). METHODS: Tissue samples from consecutive patients with subepithelial lesions collected by EUS-FNA, without analysis by on-site cytopathology, were evaluated by the same pathologist only using CBs in AAF fixative. Sections were stained with haematoxylin-eosin and underwent complementary immunohistochemical staining for SMA, CD117, DOG-1 and S100 in the presence of mesenchymal neoplasms. Specimens were defined as diagnostic when sufficient tissue was present for histopathological evaluation and immunohistochemistry analysis. If they were insufficient for complete evaluation, the specimens were considered nondiagnostic. RESULTS: Between September 2012 and December 2016, a total of 158 patients (median age: 57 years, 64.5% women) underwent EUS-FNA with an average of three needle passes for every lesion. The median lesion size was 17 mm. There were 113 mesenchymal neoplasms confirmed by immunohistochemistry (66 leiomyomas, 44 GISTs, two schwannomas, one leiomyosarcoma). The overall diagnostic yield of CBs was 84.17%. However, diagnosis was obtained in 98.5% (133/135) of the cases after exclusion of 23 cases in which EUS-FNA sampling was insufficient or without tumoural tissue. Only two mesenchymal neoplasms were not confirmed by CBs even after immunohistochemistry. CONCLUSIONS: CBs collected by EUS-FNA and analysed by immunohistochemistry showed a high diagnostic yield in patients with mesenchymal neoplasms, even without on-site cytopathology.

EUS-FNA WITH 19 OR 22 GAUGES NEEDLES FOR GASTRIC SUBEPITHELIAL LESIONS OF THE MUSCLE LAYER.

BACKGROUND: Tissue diagnosis is required for gastric subepithelial lesions for differential diagnosis of GISTs. However, there has not been consensus about the best needle for EUS-guided sampling of these lesions. AIM: To evaluate the diagnostic yield of EUS-FNA for gastric subepithelial lesions of the proper muscle layer with large-bore 19 gauge needles. METHODS: A prospectively maintained database was retrospectively reviewed to identify consecutive patients who underwent EUS-FNA with 19 and 22 gauge needles for gastric subepithelial lesions of the fourth endosonographic layer in a tertiary care referral center. EUS-FNA was performed by the same endosonographer, using the fanning technique, without on-site cytopathologist. Specimens were analysed through cell blocks by the same pathologist. Procedure results were categorized into diagnostic, defined as enough material for histopathology and immunohistochemistry, or nondiagnostic. RESULTS: Eighty-nine patients (mean age: 59 years, 77% women) underwent 92 EUS-FNA with 19 (75) or 22 (17) gauge needles. Mean lesion size was 22.6 mm. Overall diagnostic yield was 88%. The diagnostic yield of 19 gauge was higher than that of 22 gauge needle (92%x70.6%; p=0.0410), and similar for lesions >2 cm and <2 cm (93.7%x90.7%; p=0.9563). The best performance for 19 gauge needles was obtained performing <3 needle passes. Complication rate was 2.8%. CONCLUSIONS: Diagnostic yield of EUS-FNA with 19 gauge needles is 92% for gastric subepithelial lesions of the proper muscle layer. It is safe and highly valuable for differentiation between GIST and leiomyoma, no matter the size of the lesion.

Eus-fna with 19 or 22 gauges needles for gastric subepithelial lesions of the muscle layer / Punção aspirativa ecoguiada com agulhas de 19 e 22 gauges para lesões subepiteliais gástricas da camada muscular própria

ABSTRACT Background: Tissue diagnosis is required for gastric subepithelial lesions for differential diagnosis of GISTs. However, there has not been consensus about the best needle for EUS-guided sampling of these lesions. Aim: To evaluate the diagnostic yield of EUS-FNA for gastric subepithelial lesions of the proper muscle layer with large-bore 19 gauge needles. Methods: A prospectively maintained database was retrospectively reviewed to identify consecutive patients who underwent EUS-FNA with 19 and 22 gauge needles for gastric subepithelial lesions of the fourth endosonographic layer in a tertiary care referral center. EUS-FNA was performed by the same endosonographer, using the fanning technique, without on-site cytopathologist. Specimens were analysed through cell blocks by the same pathologist. Procedure results were categorized into diagnostic, defined as enough material for histopathology and immunohistochemistry, or nondiagnostic. Results: Eighty-nine patients (mean age: 59 years, 77% women) underwent 92 EUS-FNA with 19 (75) or 22 (17) gauge needles. Mean lesion size was 22.6 mm. Overall diagnostic yield was 88%. The diagnostic yield of 19 gauge was higher than that of 22 gauge needle (92%x70.6%; p=0.0410), and similar for lesions >2 cm and <2 cm (93.7%x90.7%; p=0.9563). The best performance for 19 gauge needles was obtained performing <3 needle passes. Complication rate was 2.8%. Conclusions: Diagnostic yield of EUS-FNA with 19 gauge needles is 92% for gastric subepithelial lesions of the proper muscle layer. It is safe and highly valuable for differentiation between GIST and leiomyoma, no matter the size of the lesion.

RESUMO Racional: O diagnóstico tecidual é mandatório nas lesões subepiteliais gástricas da camada muscular própria para o diagnóstico diferencial das neoplasias do estroma gastrointestinal (GISTs). Contudo, ainda não há consenso quanto a melhor agulha para a punção ecoguiada destas lesões. Objetivo: Avaliar o valor da punção aspirativa ecoguiada com agulhas calibrosas de 19 gauge para o diagnóstico diferencial das lesões subepiteliais gástricas da camada muscular própria. Métodos: Foram revisados retrospectivamente os registros de pacientes consecutivos submetidos à punção aspirativa ecoguiada com agulhas de 19 e 22 gauge de lesões subepiteliais gástricas da quarta camada ecográfica em um centro de referência. A punção aspirativa foi realizada sempre pelo mesmo endoscopista, com o emprego da técnica de fanning, sem presença de citopatologista em sala. O material aspirado foi avaliado apenas pela técnica de cell block pelo mesmo patologista. Os resultados foram considerados diagnósticos, na presença de material adequado para coloração pela H&E e imunoistoquímica, ou não-diagnósticos. Resultados: Oitenta e nove pacientes (idade média: 59 anos, 77% do sexo feminino) foram submetidos a 92 punções aspirativas ecoguiadas com agulhas de 19 (75) ou 22 (17) gauges. O tamanho médio das lesões foi de 22,6 mm. O ganho diagnóstico geral foi de 88%. O ganho diagnóstico para as agulhas de 19 gauge foi superior ao das agulhas de 22 gauge (92%x70,6%; p=0,0410), e similar para lesões >2 cm e <2 cm (93,7%x90,7%; p=0,9563). Os melhores resultados com a agulha de 19 gauge foram obtidos com a realização de até três punções. A taxa de complicações foi de 2,8%. Conclusão: O ganho diagnóstico da punção aspirativa ecoguiada de lesões subepiteliais gástricas da camada muscular própria com agulhas de 19 gauge é de 92%. A punção com a agulha mais calibrosa para lesões de qualquer tamanho é procedimento seguro e de grande valor no diagnóstico diferencial dos GISTs e leiomiomas.

Metastatic lymph node ratio, 6th or 7th AJCC edition: witch is the best lymph node classification for esophageal cancer? Prognosis factor analysis in 487 patients.

BACKGROUND: The esophageal cancer is one of the most common and aggressive worldwide. Recently, the AJCC changed the staging system, considering, among others, the important role of the lymph node metastasis on the prognosis. AIM: To discuss the applicability of different forms of lymph node staging in a western surgical center. METHODS: Four hundred eighty seven patients with esophageal cancer were enrolled. Three staging systems were evaluated, the 6th and the 7th AJCC editions and the Lymph Node Metastatic Ratio. RESULTS: The majority of the cases were squamous cell carcinoma. The mean lymph node sample was eight. Considering the survival, there was no significant difference between the patients when they were classified by the 7th AJCC edition. Analysis of the Lymph Node Metastatic Ratio, just on the group of patients with 0 to 25%, has shown significant difference (p=0,01). The 6th AJCC edition shows the major significant difference between among the classifications evaluated. CONCLUSION: In this specific population, the 7th AJCC edition for esophageal cancer was not able to find differences in survival when just the lymph node analysis was considered.

Metastatic lymph node ratio, 6th or 7th AJCC edition: witch is the best lymph node classification for esophageal cancer? Prognosis factor analysis in 487 patients / Índice de metástase linfonodal da 6a ou 7a edição do AJCC: qual é a melhor classificação linfonodal para o câncer de esôfago? Uma análise de fatores prognósticos em 487 pacientes

BACKGROUND: The esophageal cancer is one of the most common and aggressive worldwide. Recently, the AJCC changed the staging system, considering, among others, the important role of the lymph node metastasis on the prognosis. AIM: To discuss the applicability of different forms of lymph node staging in a western surgical center. METHODS: Four hundred eighty seven patients with esophageal cancer were enrolled. Three staging systems were evaluated, the 6th and the 7th AJCC editions and the Lymph Node Metastatic Ratio. RESULTS: The majority of the cases were squamous cell carcinoma. The mean lymph node sample was eight. Considering the survival, there was no significant difference between the patients when they were classified by the 7th AJCC edition. Analysis of the Lymph Node Metastatic Ratio, just on the group of patients with 0 to 25%, has shown significant difference (p=0,01). The 6th AJCC edition shows the major significant difference between among the classifications evaluated. CONCLUSION: In this specific population, the 7th AJCC edition for esophageal cancer was not able to find differences in survival when just the lymph node analysis was considered. .

RACIONAL: O câncer de esôfago é um dos mais comuns e agressivos que existem. Recentemente o AJCC mudou o sistema de estadiamento, considerando, entre outros fatores, a importância da metástase linfonodal sobre o prognóstico. OBJETIVO: Discutir a aplicabilidade de diferentes formas de estadiamento linfonodal em um serviço de cirurgia ocidental. MÉTODOS: Quatrocentos e oitenta e sete pacientes com câncer de esôfago foram arrolados. Três estadiamentos foram avaliados, a 6a e a 7a Edição do AJCC e o Índice de Metástase Linfonodal. RESULTADOS: A maioria foi casos foi composta por carcinoma epidemóide. A média de amostra linfonodal foi de oito. Considerando a sobrevida, não houve diferença significativa entre os pacientes quando foram classificados pela 7a Edição do AJCC. Analisando o Índice de Metástase linfonodal, apenas o grupo de pacientes com 0-25% mostrou diferença significativa (p=0,01). A 6a Edição do AJCC mostrou a maior diferença entre as classificações avaliadas. CONCLUSÃO: Considerando as características da amostra, a nova classificação do AJCC não foi capaz de evidenciar diferenças significativas na sobrevida dos pacientes, quando apenas o estadiamento linfonodal foi avaliado. .

Renal mixed epithelial and stromal tumor: case report / Tumor epitelial-estromal misto do rim: relato de caso

Mixed epithelial and stromal tumor (MEST) represents a recently described biphasic kidney neoplasm, which predominantly affects perimenopausal females. The authors report the case of a young male patient with a MEST exhibiting positivity for estrogen and progesterone receptors. Computed tomography/magnetic resonance imaging (CT/MRI) showed an expansive lesion affecting the right kidney. Grossly, a solid-cystic tumor was identified, which measured 5.7 × 3.5 × 2.4 cm. On microscopic examination, a biphasic tumor constituted by stromal and epithelial elements, without significant atypias, was identified. The stromal element was composed of spindle cells revealing positive immunoexpression for actin, desmin, vimentin, and estrogen receptors. The epithelial component exhibited a predominantly tubular pattern showing positive immunoreaction for cytokeratins. The diagnosis of MEST was then established.

O tumor epitelial e estromal misto (TESM) representa uma neoplasia renal bifásica descrita recentemente que afeta predominantemente mulheres na perimenopausa. Os autores relatam o caso de um paciente jovem, do sexo masculino, com TESM exibindo positividade para receptores de estrogênio e progesterona. A tomografia computadorizada/ressonância magnética (TC/RM) mostrou lesão expansiva no rim direito. Ao exame macroscópico, identificou-se tumor sólido-cístico medindo 5,7 × 3,5 × 2,4 cm. À microscopia, foi encontrado tumor bifásico constituído por elementos estromais e epiteliais, sem atipias significativas. O componente estromal era composto por células fusiformes, exibindo imunoexpressão positiva para actina, desmina, vimentina e receptores de estrogênio. Os elementos epiteliais mostraram padrão predominantemente tubular e exibiram imunorreação positiva para citoqueratinas. O diagnóstico de TESM foi então estabelecido.

Evaluation of HER2 Protein Expression Using 2 New Monoclonal Antibodies.

This study describes the performance of 2 new mouse anti-HER2 monoclonal antibodies (Abs), clones 33F and 410G, in evaluating HER2 overexpression in a series of 123 invasive breast carcinoma cases. In-house immunohistochemistry (IHC) was performed and the results were compared with those for the SP3 and A0485 anti-HER2 Abs. Chromogenic in situ hybridization was used to detect ERBB2 amplification and its concordance with IHC was analyzed. Comparison of IHC results for 33F with SP3 and A0485 yielded concordance rates (K) of 0.81 and 0.75, respectively; the same concordance rates were found when comparing results for 410G with SP3 and A0485. Compared with SP3 and A0485, 33F and 410G specificities were 98.6% and 98.6%, and 100% and 100%, respectively, whereas the sensitivities were 80% and 74.1%, and 78% and 72.2%, respectively. The K values between 33F and 410G HER2+ expression and chromogenic in situ hybridization-positive amplification were 1 and 0.96, respectively. These concordance rates were reproduced in another production batch (K=0.96 and K=0.96). Together, these results show that the tested monoclonal Abs would be well suited for detecting HER2 protein overexpression by IHC.

Tumores renais: avaliação de fatores prognósticos de 98 casos em hospital de referência de Porto Alegre, Brasil / Renal tumors: evaluation of prognostic factors in 98 cases from a reference hospital in Porto Alegre, Brazil

Introduction: Renal cell carcinoma (RCC) is an aggressive disease worldwide. Objective: Study traditional prognostic factors associated with pathological reports and the novel markers survivin and B7-H1 by immunohistochemistry. Methods: In a reference hospital of Porto Alegre, Brazil, we conducted a cross-sectional study of RCC in patients who underwent radical nephrectomy between 2006 and 2009. We selected those who were diagnosed with the most common histologic subtypes: clear cell and papillary RCC. We retrospectively reviewed pathological data to determine traditional prognostic factors, like size, presence of coagulative necrosis, Fuhrman grade and tumor-node metastasis (TNM) system. Besides, we performed an immunohistochemistry (IHC) study with survivin and B7-H1. Results: Our sample had 98 cases, 90% of the cases were composed by clear cell histologic subtype, 73% were tumors classified as T1 and T2 in the TNM system, most were Fuhrman nuclear grade 2 or 3, and 70% were positive for necrosis. In relation to the new prognostic markers, we found 50 cases positive to survivin and 38 to B7-H1. In this investigation of traditional prognostic markers and new markers we observed that only necrosis was associated with positive results of biomarkers. < 0.001). Conclusion: This finding confirms previous studies that necrosis is an important factor to consider in the prognosis of RCC...

Introdução: O carcinoma de células renais (CCR) é uma doença de comportamento agressivo em todo o mundo. Objetivo: Estudar os fatores prognósticos tradicionais identificados no exame anatomopatológico e sua correlação com a expressão imunoistoquímica dos novos marcadores survivina e B7-H1. Materiais e métodos: Em um hospital de referência de Porto Alegre, foi realizado um estudo transversal de CCR, com pacientes que realizaram nefrectomia total, no período de 2006 a 2009. Foram selecionados aqueles com os tipos histológicos mais comuns: células claras e papilares. Fatores prognósticos tradicionais foram obtidos por meio da revisão de dados patológicos relevantes dos casos, como tamanho, necrose, tipo histológico, grau nuclear e sistema tumor-linfonodo-metástase (TNM). Também se realizou estudo imunoistoquímico (IMQ) da amostra, com o uso dos marcadores survivina e B7-H1. Resultados: Obtivemos 98 casos, com 90% deles do tipo células claras, 73% classificados como T1 e T2, a maioria com grau nuclear de Fuhrman 2 e 3 e cerca de 70% da amostra positivos para necrose. Já no estudo IMQ foi encontrada positividade em 38 casos para o B7-H1 e em 50 para survivina. Ao considerarmos a associação entre os fatores prognósticos tradicionais e a expressão dos marcadores, encontramos associação somente entre o grupo positivo para os marcadores e necrose (p < 0,001). Conclusão: Tal achado vai ao encontro dos dados da literatura que vêm realçando a importância da necrose no prognóstico dos CCR...

The effect of celecoxib on the development of diethylnitrosamine-induced liver tumors in rats.

BACKGROUND/AIMS: Hepatocellular carcinoma is one of the most commonly diagnosed malignant tumors in the world, and it typically has a poor prognosis. Extensive studies have examined the effects of non-steroidal anti-inflammatory drugs selective to COX-2 on the chemoprevention of various tumors. The objective of this study is to observe the effect of celecoxib on the development of liver tumors in rats. MATERIAL AND METHODS: Hepatocellular carcinoma was induced in a group of 75 rats with the carcinogen diethylnitrosamine. The animals were divided into 5 groups. Three groups received various doses of celecoxib, one group received indomethacin, and a control group received no non-steroidal selective anti inflammatory drugs. RESULTS: The experimental model was considered to be successful because 78% of the rats in the control group developed liver tumors. The number of neoplastic lesions was similar among the celecoxib, indomethacin and control groups, although the nodule diameter of the lesions was smaller in the celecoxib group. Better results were observed in animals that received celecoxib at doses of 6 and 9 mg/kg/ day; 4 rats in these groups did not show any neoplastic histological lesions, and a greater proportion of the nodules in the other animals in these groups were benign than in the groups that did not use celecoxib. CONCLUSIONS: These results suggest that celecoxib may play a role in modifying the natural history of hepatocellular carcinoma development.

Evaluation of the C3435T polymorphism in the MDR1 gene in patients with hepatocellular carcinoma.

INTRODUCTION: Considering the high prevalence of liver tumors and the impact on patient survival, a greater understanding of the biological behavior of those tumors if of great importance. The multidrug resistance gene (MDR1) may present as single nucleotide polymorphism (SNP) which can affect the expression and activity of P-glycoprotein (Pgp), and high expression of Pgp has been associated with a worse prognosis in affected patients. OBJECTIVE: To correlate the C3435T polymorphism in the MDR1 gene with the immunohistochemical expression of Pgp. MATERIAL AND METHODS: A total of 67 samples from patients with diagnosis of hepatocellular carcinoma (HCC), collected in the period from 2000 to 2009, were analyzed. The polymorphism in the MDR1 gene was determined by the technique of allele-specific real time PCR using TaqMan assay, and the expression of protein Pgp was evaluated by immunohistochemistry. RESULTS: Among the samples evaluated, 56 (83.6%) were from male patients and 11 (16.4%) from females. Mean age was 60.6 years (± 8.8), ranging from 37 to 85 years. The etiology of the HCC was related to hepatitis C virus infection (HCV) in 31 (46.3%) of cases, followed by hepatitis C virus infection + alcohol in 24 cases (35.8%), alcohol in 4 cases (6)%, hepatitis B virus (HBV) in 4 cases (6%) and other factors in 4 cases (6%). Liver transplantation was performed in 48 cases (71.6%) and hepatectomia in 19 cases (28.4%). The genotypes CC, CT and TT showed frequencies of 25.4%, 41.8% and 32.8%, respectively, and the allele frequencies were 46.3% for allele C and 53.7% for allele T. The expression of Pgp in over 75% of the cells was significantly more frequent in tumor tissue. On the other hand, a low expression of Pgp, in less than 25% of the cells, was significantly more frequent in non-tumor tissue. The Pgp expression in more than 50% of tumor cells of individuals with genotypes CC, CT and TT was 15.7%, 51.0% and 33.3%, respectively, and was significantly higher when in the presence of allele T (p = 0.002). CONCLUSION: The presence of the polymorphic allele T is related to increased expression of Pgp protein in patients with HCC.