Change in the risk stratification of prostate cancer after Slide Review by a uropathologist: the experience of a reference center for the treatment of prostate cancer.

INTRODUCTION: Brachytherapy is an option for treating low-risk prostate cancer (PC). Biochemical control of low-risk disease can reach 95 %. The practice advocated is that a review of prostate biopsies should be mandatory before choosing the best treatment for patients with PC. Our objective was to evaluate the change in PC risk after review of a prostate biopsy by an experienced uropathologist at a reference hospital. MATERIALS AND METHODS: Between December 2003 and August 2012, 182 men were referred to our institution for brachytherapy to treat PC. Their slides were reviewed by the same uropathologist. RESULTS AND DISCUSSION: Classification risk disagreement occurred in 71 (39 %) cases, including one in which no tumor was observed. The main cause of risk change was related to the Gleason score (GS), with 57 (81.4 %) cases upgraded to GS 7 or 8. Tumor volume was also compared, although only the number of fragments was reported in most original reports. The concordance of the number of cores affected by tumor was 43.9 %, and in 49 % of the cases, the number was decreased by the uropathologist. Perineural invasion (PNI) was reported in one quarter of original reports, and the agrement was 58 %. CONCLUSION: Slide review by an uropathologist remains essential at reference radiotherapy centers for the treatment of PC. The change in PC risk evaluation is mainly due to the GS, but tumor volume and PNI, which are important for the characterization of tumor aggressiveness, are also misinterpreted and could drive a change in the therapy choice.

Change in the risk stratification of prostate cancer after Slide Review by a uropathologist: the experience of a reference center for the treatment of prostate cancer

Introduction Brachytherapy is an option for treating low-risk prostate cancer (PC). Biochemical control of low-risk disease can reach 95%. The practice advocated is that a review of prostate biopsies should be mandatory before choosing the best treatment for patients with PC. Our objective was to evaluate the change in PC risk after review of a prostate biopsy by an experienced uropathologist at a reference hospital. Materials and Methods Between December 2003 and August 2012, 182 men were referred to our institution for brachytherapy to treat PC. Their slides were reviewed by the same uropathologist. Results and Discussion Classification risk disagreement occurred in 71 (39%) cases, including one in which no tumor was observed. The main cause of risk change was related to the Gleason score (GS), with 57 (81.4%) cases upgraded to GS 7 or 8. Tumor volume was also compared, although only the number of fragments was reported in most original reports. The concordance of the number of cores affected by tumor was 43.9%, and in 49% of the cases, the number was decreased by the uropathologist. Perineural invasion (PNI) was reported in one quarter of original reports, and the agreement was 58%. Conclusion Slide review by an uropathologist remains essential at reference radiotherapy centers for the treatment of PC. The change in PC risk evaluation is mainly due to the GS, but tumor volume and PNI, which are important for the characterization of tumor aggressiveness, are also misinterpreted and could drive a change in the therapy choice. .

Light microscopical and ultrastructural characterization of black howler monkey (Alouatta caraya) ovarian follicles.

The present study describes the morphological characteristics of black howler monkey (Alouatta caraya) ovarian follicles. One ovary of an adult healthy black howler monkey was collected and processed for light and electron microscopy. Primordial, primary, secondary, tertiary and pre-ovulatory follicles were evaluated for their morphometrical aspects. The ovary of black howler monkey presented a distinct conformation with a uniform distribution of the follicles mostly in the peripheric cortex. This black howler monkey ovary presented a total of 59 921 ovarian follicles. From this amount, 71.1% were classified as primordial, 18.9% as primary, 8.1% as secondary, 1.4% as tertiary and 0.5% as pre-ovulatory follicles. From all these developmental stages, the mean diameters of follicles, oocytes, oocytes nuclei and the mean number of granulosa cells are described. Moreover, primordial, primary and secondary follicles have been observed by electron microscopy.

Overexpression of HER2/neu oncoprotein in cytologic specimens.

OBJECTIVE: To assess the rate of HER2/neu overexpression in cytologic specimens by immunocytochemistry (ICC) and compare these results in matched surgical specimens by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH), when available. STUDY DESIGN: All cytologic specimens processed for HER2/neu evaluation by ICC (72 cases) and available corresponding histologic specimens (16 cases) were retrieved from our files. ICC was applied to previously Papanicolaou stained, routine fine needle aspirations specimens (64 cases) and cytocentrifuged, alcohol-fixed, fluid specimens (8 cases). FISH was performed on 6 histologic specimens. RESULTS: Overexpression of HER2/neu was seen in 7/22 breast cancers (31.8%), 3/18 pulmonary adenocarcinomas (16.6%), 2/5 colorectal adenocarcinomas (40%), 1/2 adenocarcinomas of the biliary system (50%), 1/3 thyroid papillary carcinomas (33.3%) and 1/3 prostate adenocarcinomas (33.3%). Sixteen cases had IHC in matched histologic specimens: 14 (87.5%) cases were concordant (11 negative and 3 positive in both specimens), 1 case was negative in the cytologic specimen and positive in the histologic specimen (with no amplification by FISH), and 1 case was positive in the cytologic specimen and negative in the histologic specimen (not informative by FISH). CONCLUSION: Our data suggest that overexpression of HER2/neu oncoprotein can be successfully detected in routine cytologic specimens, providing a simple, fast and cost-effective method of selecting patients for specific treatment.

Lack of mutations of exon 2 of the MEN1 gene in endocrine and nonendocrine sporadic tumors.

In addition to the mutations that underlie most cases of the multiple endocrine neoplasia type 1 (MEN1) syndrome, somatic mutations of the MEN1 gene have also been described in sporadic tumors like gastrinomas, insulinomas and bronchial carcinoid neoplasm. We examined exon 2 of this gene, where most of the mutations have been described, in 148 endocrine and nonendocrine sporadic tumors. DNA was obtained by phenol/chloroform extraction and ethanol precipitation from 92 formalin-fixed, paraffin-embedded samples, and from 40 fresh tumor tissue samples. We used 5 pairs of primers to encompass the complete coding sequence of exon 2 of the MEN1 gene that was screened by the polymerase chain reaction-single-stranded conformation polymorphism (PCR-SSCP) technique in 78 sporadic thyroid cancers: 28 follicular adenomas, 35 papillary carcinomas, 14 follicular carcinomas, and 1 anaplastic thyroid carcinoma. We also examined 46 adrenal lesions (3 hyperplasias, 3 adenomas and 35 adrenocortical carcinomas, 2 pheochromocytomas, 2 ganglioneuroblastomas, and 1 lymphoma) and 24 breast cancers (6 noninvasive, 16 infiltrating ductal, and 2 invasive lobular tumors). The PCR product of 5 tumors suspected to present band shifts by SSCP was cloned. Direct sense and antisense sequencing did not identify mutations. These results suggest that the MEN1 gene is not important in breast, thyroid or adrenal sporadic tumorigenesis. Because the frequency of mutations varies significantly among tumor subgroups and allelic deletions are frequently observed at 11q13 in thyroid and adrenal cancers, another tumor suppressor gene residing in this region is likely to be involved in the tumorigenesis of these neoplasms.

Lack of mutations of exon 2 of the MEN1 gene in endocrine and nonendocrine sporadic tumors

In addition to the mutations that underlie most cases of the multiple endocrine neoplasia type 1 (MEN1) syndrome, somatic mutations of the MEN1 gene have also been described in sporadic tumors like gastrinomas, insulinomas and bronchial carcinoid neoplasm. We examined exon 2 of this gene, where most of the mutations have been described, in 148 endocrine and nonendocrine sporadic tumors. DNA was obtained by phenol/chloroform extraction and ethanol precipitation from 92 formalin-fixed, paraffin-embedded samples, and from 40 fresh tumor tissue samples. We used 5 pairs of primers to encompass the complete coding sequence of exon 2 of the MEN1 gene that was screened by the polymerase chain reaction-single-stranded conformation polymorphism (PCR-SSCP) technique in 78 sporadic thyroid cancers: 28 follicular adenomas, 35 papillary carcinomas, 14 follicular carcinomas, and 1 anaplastic thyroid carcinoma. We also examined 46 adrenal lesions (3 hyperplasias, 3 adenomas and 35 adrenocortical carcinomas, 2 pheochromocytomas, 2 ganglioneuroblastomas, and 1 lymphoma) and 24 breast cancers (6 noninvasive, 16 infiltrating ductal, and 2 invasive lobular tumors). The PCR product of 5 tumors suspected to present band shifts by SSCP was cloned. Direct sense and antisense sequencing did not identify mutations. These results suggest that the MEN1 gene is not important in breast, thyroid or adrenal sporadic tumorigenesis. Because the frequency of mutations varies significantly among tumor subgroups and allelic deletions are frequently observed at 11q13 in thyroid and adrenal cancers, another tumor suppressor gene residing in this region is likely to be involved in the tumorigenesis of these neoplasms

Abnormal expression of MDM2 in prostate carcinoma.

Mutation of p53 is rare in localized prostate carcinoma. The oncoprotein MDM2, whose gene has a response element for p53, promotes the degradation of p53 protein and inhibits its transcriptional activation of genes related to cell cycle arrest and apoptosis, constituting a negative feedback control. We studied p53 and MDM2 expression by immunohistochemistry and looked for mutations in p53 exons 5 to 8 by polymerase chain reaction-single strand conformational polymorphism in 118 patients submitted to radical prostatectomy for localized prostate cancer. In 28 cases, we studied cell proliferation by immunohistochemistry, using antibody for Ki-67, and apoptosis by the deoxynucleotidyl transferase mediated dUTP biotin nick end labeling technique. Although no p53 mutations were found, p53 protein was detected in 31.4% of the cases, and these cases had higher Gleason scores (P = .03) and more advanced tumor stages (P = .02). MDM2 was overexpressed in 40.7% of the cases, and these cases had greater tumor volumes (P = .001). Tumors that were positive for both p53 and MDM2 were larger (P = .003) and of more advanced stage (P = .03). Within the 28-case subset, the proliferative index was higher among MDM2-positive tumors (P = .046), and the apoptotic index was lower among p53-positive tumors (P = .01). We conclude that, although p53 mutation is a rare event in prostate carcinogenesis, the detection of p53 protein by immunohistochemistry is common and is associated with decreased apoptosis and increased histologic grade and tumor stage. We also conclude that the overexpression of MDM2 has a role in prostate carcinogenesis, being frequently detected and associated with increased cell proliferation and tumor volume. Finally, we propose that the MDM2-positive/p53-positive phenotype identifies prostate cancers with aggressive behavior.

Differences in tumour growth, tumour cell proliferation and immune function after laparoscopy and laparotomy in an animal model.

BACKGROUND: Clinical and experimental studies have shown that laparoscopy preserves the immune response and can give better clinical results than laparotomy. However, the use of laparoscopy for the treatment of cancer patients is still controversial due to the risk of port-site and haematogenous metastases and increased tumour growth. The purpose of this experimental study was to assess tumour growth and the mechanism of differential tumour behaviour after laparoscopy and laparotomy. METHODS: Seventy-five young, male Wistar rats were randomly assigned to one of two experiments. Experiment 1: 45 animals were inoculated subcutaneously with Walker carcinosarcoma 256 cells and were subdivided into three groups of 15 rats. Control group la was submitted to anaesthesia only, group 1b received carbon dioxide (CO(2)) pneumoperitoneum,while group 1c received a laparotomy. Animals were sacrificed on postoperative day (POD) 7; tumours were excised and weighed to evaluate tumour growth. Nucleolar organiser regions identified by silver staining (AgNORs) were analysed to evaluate cell proliferation. Experiment 2: 30 rats were submitted to the same procedures as before, with ten animals in each group (2a, 2b, 2c), and a delayed-type hypersensitivity response (DTH) was used to evaluate the immune function. RESULTS: The average tumour mass was 1.76 g in group 1a, 2.81 g in group 1b and 4.21 g in group 1c (p < 0.05). The AgNOR expression results were similar in the three groups. The immune function was better preserved in the control group (2a: average inflammatory area on POD1 = 106 mm(2) and on POD2 = 128.18 mm(2)), than in the pneumoperitoneum group (2b: average inflammatory area on POD1 = 79.75 mm(2) and on POD2 = 126.93 mm(2)); the worst results were in the laparotomy group (2c: average inflammatory area on POD1 = 33.33 mm(2) and on POD2 = 61.32 mm(2)).There were significant differences between groups 2a and 2c and between 2b and 2c. CONCLUSION: Laparotomy stimulates a greater tumour growth than CO(2) pneumoperitoneum, but there is no difference in tumour cell proliferation. The cellular immune function is better preserved in animals submitted to CO pneumoperitoneum than in the laparotomized animals. These results suggest a relationship between a weaker immune response and a greater tumour growth.

Monoclonality of asynchronous bilateral lymphoma of the testis.

OBJECTIVES: Lymphoma is the most frequent testicular malignancy in men over 60 years of age. Even though patients present initially with localized disease, the high incidence of bilateral involvement, synchronous or not, and early systemic dissemination are characteristic of these neoplasms. Sometimes the interval between tumor involvement of both testes is long. The question is raised whether either the patient has a predisposition to present new clones of transformed lymphocytes, or the same disease using the same pathway from a systemic reservoir infiltrates the contralateral testis. METHOD: Polymerase chain reaction and DNA sequencing were used to detect immunoglobulin heavy chain (IgH) rearrangement in paraffin-embedded specimens from asynchronous tumors affecting the right and left testis of a 85-year-old man with an interval period of 13 months. RESULTS: Both tumors showed the same IgH rearrangement. CONCLUSIONS: The lymphoma affecting the left and right testis derived from the same clone. It makes a strong case that lymphoma of the testis is the first manifestation of a systemic disease and should be treated aggressively early at the beginning of the disease.

[Histological criteria of esophagitis in the gastroesophageal reflux disease. Reevaluation of the sensitivity of the esophageal 24-hours pHmetry]. / Critérios histológicos de esofagite na doença do refluxo gastroesofágico. Reavaliação da sensibilidade da pHmetria esofágica de 24 horas.

Little change was observed in the histological criteria of reflux esophagitis since the studies of Ismail-Beiji, Pope (1970) and Weinstein (1975). The 24-hour esophageal pHmetry has been proposed as a high sensitivity method in diagnosis of gastroesophageal reflux disease patients. In this study we selected 35 patients with histological esophagitis and submitted them to 24-hour esophageal pHmetry. We determined histological differences according to reflux pattern, endoscopic esophagitis grades and age. The sensitivity of 24-hour esophageal pHmetry was 60.0% in our patients. There are higher histological alterations in patients with more severe patterns of reflux (supine and combined) and significant difference (P < 0.05) in observed quantitative exocytosis between moderate and severe endoscopic esophagitis. There are no difference between histological esophagitis criteria and age groups.

No relationship between proliferative activity and the MACIS prognostic scoring system in papillary thyroid carcinoma.

BACKGROUND: The MACIS score uses metastasis, age, completeness of resection, local invasion, and tumor size to stratify patients with papillary thyroid carcinoma (PTC) into four groups with different survival. METHODS: Immunostaining for proliferating cell nuclear antigen (PCNA) was done in 43 cases of PTC. Relationships between proliferative index (percentage of cells that were PCNA positive) and the MACIS parameters were examined. Double staining for PCNA and for silver-stained nucleolar organizer regions (AgNORs, indicating proliferation) was performed in 10 cases. RESULTS: PCNA was detected only in tumor cells. The proliferative index was low (mean, 14.2%; median, 13.0%), did not differ between MACIS groups (p = 0.56), and showed no association with individual MACIS parameters. PCNA immunostaining correlated with AgNOR staining. The mean AgNOR count was 2.28 in PCNA-positive cells and 1.85 in PCNA-negative cells (p

Analysis of p53 expression and proliferative assessment using PCNA in localized prostate carcinoma.

The surgical specimens from 51 men submitted to radical prostatectomy for localized prostate cancer were examined by immunohistochemistry using proliferation cell nuclear antigen (PCNA) monoclonal antibody to evaluate the proliferative index (PI). The relationship between PI, biological variables and p53 protein expression was evaluated by immunohistochemistry. PI was low in invasive localized prostate carcinoma (mean, 12.4%) and the incidence of PCNA-positive cells was significantly higher in tumors with p53 expression (P = 0.0226). There was no statistical difference in PCNA values when biological parameters such as Gleason score, tumor volume, extraprostatic involvement, seminal vesicle infiltration or lymph node metastasis were considered. We conclude that proliferative activity is usually low in prostate carcinoma but is correlated with p53 immune staining, indicating that p53 is important in cell cycle control in this neoplasm.

Analysis of p53 expression and proliferative assessment using PCNA in localized prostate carcinoma

The surgical specimens from 51 men submitted to radical prostatectomy for localized prostate cancer were examined by immunohistochemistry using proliferation cell nuclear antigen (PCNA) monoclonal antibody to evaluate the proliferative index (PI). The relationship between PI, biological variables and p53 protein expression was evaluated by immunohistochemistry. PI was low in invasive localized prostate carcinoma (mean, 12.4percent) and the incidence of PCNA-positive cells was significantly higher in tumors with p53 expression (P = 0.0226). There was no statistical difference in PCNA values when biological parameters such as Gleason score, tumor volume, extraprostatic involvement, seminal vesicle infiltration or lymph node metastasis were considered. We conclude that proliferative activity is usually low in prostate carcinoma but is correlated with p53 immune staining, indicating that p53 is important in cell cycle control in this neoplasm

[Carcinoid tumors of the common bile duct: report of a case]. / Tumor carcinóide de ducto biliar comum: relato de um caso.

The authors discuss an uncommon case in the literature of a carcinoid tumor of in the bifurcation of common hepatic duct. The tumor was surgically resected and the duct was reconstructed by Y of Roux's technic. The patient had a good evolution and no tumoral lesion was found in post operative exams during the last six months. The authors present a literature review and discuss diagnosis, treatment and prognosis.

Genetics and colorectal cancer (HNPCC) in adolescence. A case report.

The authors report a case of non-polyposis colon cancer in a seventeen year old female without prior polyposis or family history. Since it was the first case in this family, HNPCC was suspected. The polymerase chain reaction (PCR) of the tumor revealed changes in four polymorphic regions. Analysis of two of them, indicated the loss of genetic material confirming instability suggestive of HNPCC. The patient underwent ileorectal anastomosis and adjuvant chemotherapy with a good outcome. The authors discuss the importance of family history, genetic and immunohistochemistry studies, and the instability of microsatellites in adolescents with colorectal cancer.

Synchronous primary malignant lymphoma and carcinoma of the stomach

A case of synchronous concurrent carcinoma and primary malignant lymphoma developing as two independent tumors of the stomach is presented. The clinical and pathological diagnosis and therapeutic problemas associated with synchronous tumors of the stomach are discussed. A possible relationship between the two tumors and the role of Helicobacter pylori are also reviewed.

Synchronous primary malignant lymphoma and carcinoma of the stomach.

A case of synchronous concurrent carcinoma and primary malignant lymphoma developing as two independent tumors of the stomach is presented. The clinical and pathological diagnosis and therapeutic problems associated with synchronous tumors of the stomach are discussed. A possible relationship between the two tumors and the role of Helicobacter pylori are also reviewed.

[Clinical and laboratory evaluation of patients treated with oral anticoagulation]. / Avaliação clínica e laboratorial de pacientes em uso de anticoagulantes orais.

PURPOSE: To evaluate the clinical and laboratory management of patients taking anti-vitamin K drugs (AVK). METHODS: We studied retrospectively 952 visits of 100 outpatients taking AVK drugs for 7.6 months. There were 56 men and 44 women, 54 patients had acute arterial occlusion, 34 presented venous thromboembolism and 12 had cardiopathy. Anticoagulation level was estimated by the prothrombin time reported as international normalized ratio (INR). RESULTS: Seventy-three patients were considered stable, as they had one visit every at least 3 weeks, and their INR was within the therapeutic range in 59% of their visits, whereas 27 patients were less stable and had 36% of their visits within the therapeutic range. Insufficient anticoagulation was due to poor compliance (22%), vitamin K rich diet (19%) and underdosage (16%). Four patients presented minor bleedings, and there was no recurrence of thromboembolism. CONCLUSION: Careful clinical and laboratory management, using the INR, are necessary to avoid hemorrhage and thrombotic complications in patients taking oral anticoagulants.

Avaliaçäo clínica e laboratorial de pacientes em uso de anticoagulantes orais / Clinical and Laboratory Management of Patients Under Oral Anticoagulation

Objetivo - Avaliar o acompanhamento clínico e laboratorial de pacientes em uso de drogas antivitamina K(AVK). MÉTODOS - Foram avaliados, retrospectivamente, 952 consultas ambulatoriais de 100 pacientes em uso de AVK, durante 7,6 meses. Havia 56 homens e 44 mulheres, 54 pacientes com obstruçäo arterial aguda, 34 com troboembolismo venoso e 12 com cardiopatia. O nível de anticoagulaçäo foi medido pelo tempo de protrombina expresso em razäo normalizada internacional (RNI). RESULTADOS - Nível adequado de anticoagulaçäo foi observado em 59 "por cento" das consultas dos 73 pacientes considerados estáveis, com intervalo entre consultas maior do que 3 semanas. Os 27 pacientes instáveis tinham 36 "por cento" das consultas com RNI adequado. Anticoagulaçäo insuficiente ocorreu por uso irregular (22 por cento), dieta rica em vitamina (19 por cento) e dose insuficiente (16 por cento). Quatro pacientes tiveram sangramento sem gravidade e näo houve recorrência da trombose durante o período de observaçäo. CONCLUSÄO - O controle clínico e laboratorial, através do RNI, é fundamental para evitar complicaçöes hemorrágicas ou trombóticas em pacientes que necessitam de anticoagulaçäo oral.

[Clinical, biochemical and histopathological development of post-transfusional non-A, non-B hepatitis from the acute picture to chronicity during 13.3 years]. / Evolução clínico-bioquímica e histopatologica de hepatite não-A, não-B pós-transfusional, do quadro agudo até a cronicidade, com duração de 13.3 anos.

This case was of a 45 year old female patient with a post-transfusion non-A non-B hepatitis which was accompanied since an acute phase to hepatic cirrhosis during a period of 159.7 months or 13.3 years. Four hepatic biopsies were carried out and they divided the follow-up into 5 evolutive periods. The biopsies revealed a progressive histologic from chronic persistent hepatitis to an active chronic hepatitis and cirrhosis. The aminotransferases followed a floating course in the whole period, with ALT greater than AST starting from the 3rd period. The 3rd period (from 5th to 8th year) was of least activity of the aminotransferases, and the 4th and 5th periods (from 8th to 13th year) showed the highest activity of ALT. The 2nd period (from 3rd to 5th year) showed the least portion of gamma globulin and the highest of albumin in comparison with the others. There was no connection between the levels of aminotransferases and the values of gamma globulin and albumin in the follow up process. The treatment employed in the 5th evolutive period (prednisone and colchicine) did not present any biochemical improvement.