Prognostic Factors of Long-term Survival Following Radical Resection for Ampullary Carcinoma.

BACKGROUND: The incidence of adenocarcinoma of the ampulla of Vater has been increasing over the past years. Nevertheless, it is still a rare disease and the prognostic factors predicting long-term survival are not sufficiently clarified. This study aims to evaluate the association between histopathological characteristics and long-term survival of patients with ampullary cancer after curative resection, as well as the efficiency of immunohistochemical expression of CK7, CK20, and CDX2 to distinguish the histopathological (intestinal or pancreaticobiliary) patterns. METHODS: Demographic, histopathological data, pTNM stage, and immunohistochemical expression patterns were collected from 65 patients with adenocarcinoma of the ampulla of Vater. Five and 10-year overall and disease-free survival rates after curative resection were determined. RESULTS: Of the 65 patients with ampullary carcinoma, 47 (72%) underwent radical resection. The 5- and 10-year overall survival rate was 46% and 37%, respectively. Our results demonstrate that the main prognostic factors were the presence and number of lymph node metastases, lymph node ratio (LNR), differentiation grade, and lymphovascular invasion. After multivariate analysis, only lymph node ratio ≥ 20% remained an independent prognostic factor of survival (HR: 2.63 95% CI: 1.05-6.61; p = 0.039). CONCLUSION: Here, we demonstrated more evidence that the lymph node metastases are associated with poor prognosis in ampullary carcinoma. Particularly, the relation between the number of metastatic lymph nodes and the number of harvested lymph node (LNR) should be considered a major prognostic factor.

Potential roles of Helicobacter pylori treatment, body mass index and waist circumference in the causation of erosive esophagitis: a randomized clinical trial (HEROES-GERD).

BACKGROUND: In recent decades, the prevalence of gastroesophageal reflux disease (GERD) and obesity has been increasing while Helicobacter pylori infection has been decreasing. OBJECTIVE: To evaluate if H. pylori treatment, excess body weight and other anthropometric measurements are associated with incident erosive esophagitis, as a secondary objective of a trial which tested the efficacy of treatment of H. pylori on the symptoms of functional dyspepsia. SUBJECTS/METHODS: Upper gastrointestinal endoscopy and anthropometric assessments were performed, at baseline and after 12 months, in H. pylori positive patients with functional dyspepsia who had no baseline reflux symptoms or esophagitis. Patients were randomly assigned to receive omeprazole, amoxicillin, and clarithromycin (antibiotic group; n = 201) or omeprazole plus placebo (control group; n = 203). The primary outcome was the incidence of esophagitis 12 months after randomization, according to treatment groups, and the association of BMI and other anthropometric measurements. RESULTS: Four hundred and four patients were included (mean age, 46.1 years; 78.7% women). The 12-month follow-up endoscopic esophagitis rates for the antibiotic and control groups were 10.9% (22/201) and 9.4% (19/203), respectively (p = 0.60). The number needed to harm was 67. Baseline anthropometric measurements were performed in 94% (380/404) of patients. The 12-month follow-up esophagitis rates for overweight and normal body weight patients were 13.6% (29/213) and 6.0% (10/167), respectively (p = 0.015); rates for patients with and without increased baseline waist circumference were 15.4% (24/156) and 6.7% (15/224), respectively (p = 0.006). Following logistic regression, only the combination of increased baseline body mass index and waist, but not H. pylori treatment, was independently associated with new-onset esophagitis (OR 2.88; 95% CI: 1.28-6.45). CONCLUSIONS: Excess body weight and concomitant increased waist circumference, but not H. pylori treatment, predicts new-onset esophagitis.

Study on the organization of cellular elements in the granulomatous lesion caused by chromoblastomycosis.

BACKGROUND: Chromoblastomycosis is a deep fungal infection characterized by a complex cellular granuloma. The aim of this study was to analyze the arrangement of cells responsible for the granuloma configuration of this disease by semiquantification of the cellular components of chromoblastomycosis skin biopsies. METHODS: The cells of cutaneous biopsies slides from 100 patients with untreated chromoblastomycosis were stained with hematoxylin-eosin and the granuloma cells were evaluated by microscopic examination of the elements of each granuloma and semiquantified the number of cells through its expressivity in crosses and the histopathological variables. Their presence were coded in degrees of intensity and classified in two categories: low expression and high expression. The cells that constituted the granulomas were separated into three groups: A, B and C. RESULTS: The chromoblastomycotic granuloma analyzed by this semiquantification of its cellular components showed that there was high expression of the elements setting up a mixed organized mycotic granuloma. It was observed that mononuclear phagocytic system (A), polymorphonuclear phagocytic system (B) and lymphoplasmocytic infiltrate (C) were located around the fungus. CONCLUSION: The results indicated that the granuloma present in the cutaneous lesion of chromoblastomycosis is a mixed organized mycotic granuloma with high expression of the cellular components.

Histopathological grading of breast ductal carcinoma in situ: validation of a web-based survey through intra-observer reproducibility analysis.

BACKGROUND: Histopathological grading diagnosis of ductal carcinoma in situ (DCIS) of the breast may be very difficult even for experts, and it is important for therapeutic decisions. The challenge may be due to the inaccurate and/or subjective application of the diagnosis criteria. The aim of this study was to investigate the intra-observer agreement between a traditional method and a developed web-based questionnaire for scoring breast DCIS. METHODS: A cross-sectional study was carried out to evaluate the diagnostic agreement of an electronic questionnaire and its point scoring system with the subjective reading of digital images for 3 different DCIS grading systems: Holland, Van Nuys and modified Black nuclear grade system. Three pathologists analyzed the same set of digitized images from 43 DCIS cases using two different web-based programs. In the first phase, they accessed a website with a newly created questionnaire and scoring system developed to allow the determination of the histological grade of the cases. After at least 6 months, the pathologists read again the same images, but without the help of the questionnaire, indicating subjectively the diagnoses. The intra-observer agreement analysis was employed to validate this innovative web-based survey. RESULTS: Overall, diagnostic reproducibility was similar for all histologic grading classification systems, with kappa values of 0.57 ± 0.10, 0.67 ± 0.09 and 0.67 ± 0.09 for Holland, Van Nuys classification and modified Black nuclear grade system respectively. Only two 2-step diagnostic disagreements were found, one for Holland and another for Van Nuys. Both cases were superestimated by the web-based survey. CONCLUSION: The diagnostic agreement between the web-based questionnaire and a traditional method, both using digital images, is moderate to good for Holland, Van Nuys and modified Black nuclear grade system. The use of a scoring point system does not appear to pose a major risk of presenting large (2-step) diagnostic disagreements. These findings indicate that the use of this point scoring system in this web-based survey to grade objectively DCIS lesions is a useful diagnostic tool.

The Quinovic Acid Glycosides Purified Fraction from Uncaria tomentosa Protects against Hemorrhagic Cystitis Induced by Cyclophosphamide in Mice.

Uncaria tomentosa is widely used in folk medicine for the treatment of numerous diseases, such as urinary tract disease. Hemorrhagic cystitis (HE) is an inflammatory condition of the bladder associated with the use of anticancer drugs such as cyclophosphamide (CYP). Sodium 2-mercaptoethanesulfonate (Mesna) has been used to prevent the occurrence of HE, although this compound is not effective in established lesions. It has been demonstrated that the purinergic system is involved in several pathophysiological events. Among purinergic receptors, P2X7 deserves attention because it is involved in HE induced by CYP and, therefore, can be considered a therapeutic target. The objective of this study was to investigate the potential therapeutic effect of the quinovic acid glycosides purified fraction (QAPF) from U. tomentosa in the mouse model of CYP-induced HE. Pretreatment with QAPF not only had a protective effect on HE-induced urothelial damage (edema, hemorrhage and bladder wet weight) but was also able to control visceral pain, decrease IL-1ß levels and down-regulates P2X7 receptors, most likely by inhibit the neutrophils migration to the bladder. This research clearly demonstrates the promising anti-inflammatory properties of QAPF, supporting its use as complementary therapy. QAPF represents a promising therapeutic option for this pathological condition.

Long-Term Comparison of Aesthetical Outcomes After Oncoplastic Surgery and Lumpectomy in Breast Cancer Patients.

BACKGROUND: Lumpectomy may result in major deformities and asymmetries in approximately one-third of patients. Although oncoplastic surgery (OP) could be a useful alternative to avoid them, lack of strong data is causing some debate. The purpose of this study was to compare aesthetic outcomes in patients undergoing OP versus lumpectomy using three different assessment methods. METHODS: A total of 122 patients were included in this cross-sectional multicentric study; 57 underwent OP (46.7 %), and 65 underwent lumpectomy (53.3 %). Two breast surgeons and two plastic surgeons from different institutions using the Garbay scale independently evaluated aesthetic outcomes. BCCT.core software was applied in both groups, and the patients evaluated their aesthetic outcomes answering a questionnaire about their satisfaction rate. RESULTS: OP group had a higher proportion of excellent aesthetic results according to the BCCT.core software analysis (p = 0.028) and the specialists (p = 0.002). Multifactorial analyses showed that age ≥70 years (RP = 6.02; 95 % confidence interval [CI] 1.73-21.0; p = 0.005), tumors in the medial, inferior, and central quadrants (RP = 4.21; 95 % CI 1.88-9.44; p < 0.001), and large breasts (RP = 7.55; 95 % CI 2.48-23.0; p < 0.001) were significant risk factors for poor aesthetic outcomes after lumpectomy. The patients classified their results as better than those by the specialists and by the software, with no statistical difference between the groups. CONCLUSIONS: Excellent aesthetic results were more frequent in the OP group according to BCCT.core software analysis and specialists. In addition, some clinical conditions and tumor locations in the breast can be considered risky factors for poor aesthetic outcomes in lumpectomy.

Avaliação dos resultados estéticos e de qualidade de vida após tratamento cirúrgico do câncer de mama / Evaluation of the aesthetical and quality of life results after breast cancer surgery

Nos últimos anos, observamos tratamentos cada vez mais conservadores, tanto na mama, como na axila, com uma ampliação nos critérios de cirurgias conservadoras, associação das técnicas de oncoplástica, tratamentos radioterápicos mais direcionados e tratamentos quimioterápicos e hormonais menos agressivos. Todos esses esforços têm como objetivo central melhorar os resultados estéticos e a qualidade de vida das pacientes com câncer de mama. Portanto, tanto a avaliação dos resultados estéticos como da qualidade de vida podem auxiliar os profissionais de saúde e as pacientes nas tomadas de decisões e na abordagem de problemas específicos. Entretanto ainda existem limitações importantes nos métodos existentes de avaliação e o objetivo desta revisão foi apresentar os mesmos, bem como trazer suas principais vantagens e dificuldades para sua aplicação.

In the past years, it is observed that breast cancer treatment is becoming more conservative in the breast and in the axilla, and with the addition of oncoplastic techniques, the indications for breast conserving treatment are enlarged. In addition to that, there are advances in radiotherapy and less agressive adjuvant treatments too. All these efforts have a central aim: to improve the aesthetical results and quality of life of breast cancer patients. Soo, both the evaluation of aesthetical results and quality of life can help doctors and patients in their decisions. However, remains important limitations in current methods of evaluation and the aim of this review was to present them, and to show their advantages and difficulties in their aplicattion.

Gene expression of leptin and long leptin receptor isoform in endometriosis: a case-control study.

In this study, leptin/BMI ratio in serum and peritoneal fluid and gene expression of leptin and long form leptin receptor (OB-RL) were assessed in eutopic and ectopic endometria of women with endometriosis and controls. Increased serum leptin/BMI ratio was found in endometriosis patients. Leptin and OB-RL gene expression was significantly higher in ectopic versus eutopic endometrium of patients and controls. A positive, significant correlation was observed between leptin and OB-RL transcripts in ectopic endometria and also in eutopic endometria in endometriosis and control groups. A negative and significant correlation was found between OB-RL mRNA expression and peritoneal fluid leptin/BMI ratio only in endometriosis. These data suggest that, through a modulatory interaction with its active receptor, leptin might play a role in the development of endometrial implants.

Ectonucleotidases in tumor cells and tumor-associated immune cells: an overview.

Increasing evidence points out that genetic alteration does not guarantee the development of a tumor and indicates that complex interactions of tumor cells with the microenvironment are fundamental to tumorigenesis. Among the pathological alterations that give tumor cells invasive potential, disruption of inflammatory response and the purinergic signaling are emerging as an important component of cancer progression. Nucleotide/nucleoside receptor-mediated cell communication is orchestrated by ectonucleotidases, which efficiently hydrolyze ATP, ADP, and AMP to adenosine. ATP can act as danger signaling whereas adenosine, acts as a negative feedback mechanism to limit inflammation. Many tumors exhibit alterations in ATP-metabolizing enzymes, which may contribute to the pathological events observed in solid cancer. In this paper, the main changes occurring in the expression and activity of ectonucleotidases in tumor cells as well as in tumor-associated immune cells are discussed. Furthermore, we focus on the understanding of the purinergic signaling primarily as exemplified by research done by the group on gliomas.

Assessment of the Fournier(®) cervical specimen self-sampling device using the Papanicolaou method.

INTRODUCTION: Communities of socially excluded immigrant women, especially Muslim, Asian, Aboriginal and Maroon, are among the groups of women with low rates of cervical screening. Exclusion of the pelvic examination could result in a higher acceptance of the cervical screening among these communities and an increase in screening coverage. AIM: To assess the performance of the Fournier(®) cervical specimen self-sampling device for the cytological diagnosis of precursor or neoplastic lesions in the uterine cervix using the Papanicolaou method. METHODS: A case-control study was conducted at the Cervical Pathology Outpatient Clinic. Liquid-based cytology slides were obtained by the Fournier device and stained using the Papanicolaou method. The slides were analyzed by two pathologists, blinded for the colposcopic and histological results and compared to Papanicolaou smears that were obtained using the traditional method of speculum examination. RESULTS: There were 68 patients who were considered free from precursor or neoplastic cervical lesions. There were 35 cases of low-grade lesions, 13 cases of high-grade lesions and 3 cases of squamous-cell carcinoma. According to the first and second pathologists, the sensitivities of the device for identifying precursor or neoplastic cervical lesions were 50.0 and 60.0%, and the specificities of the method were 81.8 and 73.8%. According to the first and second pathologists, the positive predictive values of the diagnostic test were 0.67 and 0.63, and the negative predictive values were 0.68 and 0.71, respectively. CONCLUSION: Sensitivity and specificity of the Fournier device test was comparable to Papanicolaou smears tests obtained using the traditional method with speculum examination.

Periodontal disease treatment and risk of preterm birth: a systematic review and meta-analysis.

The events leading to preterm birth are still not completely understood. A quantitative systematic review was performed to estimate the effects of periodontal care during pregnancy on preventing preterm birth and low birth weight. The meta-analysis included randomized trials with pregnant women with a diagnosis of periodontal disease before 20 weeks of gestation. Relative risk (RR) with 95% confidence intervals (95%CI) was calculated. We evaluated the reduction in preterm and low birth weight. Thirteen trials were included, comparing 3,576 women in intervention groups with 3,412 women receiving usual care. The meta-analysis of the effects of periodontal disease treatment during pregnancy indicated a non-significant reduction in preterm births (RR = 0.90; 95%CI: 0.68-1.19) and low birth weights (RR = 0.92; 95%CI: 0.71-1.20). The creation and examination of a funnel plot revealed clear evidence of publication bias. In summary, primary periodontal care during pregnancy cannot be considered an efficient way of reducing the incidence of preterm birth.

Periodontal disease treatment and risk of preterm birth: a systematic review and meta-analysis / Tratamento de doença periodontal e risco de parto prematuro: revisão sistemática e metanálise

The events leading to preterm birth are still not completely understood. A quantitative systematic review was performed to estimate the effects of periodontal care during pregnancy on preventing preterm birth and low birth weight. The meta-analysis included randomized trials with pregnant women with a diagnosis of periodontal disease before 20 weeks of gestation. Relative risk (RR) with 95% confidence intervals (95%CI) was calculated. We evaluated the reduction in preterm and low birth weight. Thirteen trials were included, comparing 3,576 women in intervention groups with 3,412 women receiving usual care. The meta-analysis of the effects of periodontal disease treatment during pregnancy indicated a non-significant reduction in preterm births (RR = 0.90; 95%CI: 0.68-1.19) and low birth weights (RR = 0.92; 95%CI: 0.71-1.20). The creation and examination of a funnel plot revealed clear evidence of publication bias. In summary, primary periodontal care during pregnancy cannot be considered an efficient way of reducing the incidence of preterm birth.

Os eventos que levam à prematuridade ainda não são completamente compreendidos. Foi realizada uma revisão sistemática quantitativa para avaliar os efeitos do tratamento de doença periodontal durante a gravidez para prevenir o nascimento prematuro e baixo peso ao nascer. A metanálise incluiu estudos randomizados de grávidas com diagnóstico de doença periodontal antes de 20 semanas de gestação. O risco relativo (RR) com intervalos de 95% de confiança (IC95%) foi calculado. Avaliou-se os desfechos prematuridade e baixo peso ao nascer. Foram incluídos 13 estudos, comparando 3.576 mulheres em grupos de intervenção com 3.412 mulheres que receberam tratamento habitual. A metanálise mostrou uma redução não significativa nos partos prematuros (RR = 0,90; IC95%: 0,68-1,19) e baixo peso ao nascer (RR = 0,92; IC95%: 0,71-1,20). O gráfico de funil revelou clara evidência de viés de publicação. Em resumo, o tratamento periodontal em mulheres grávidas não pode ser considerado uma forma eficiente de reduzir a incidência de parto prematuro ou baixo peso ao nascer.

Ki-67 Antigen Overexpression Is Associated with the Metaplasia-Adenocarcinoma Sequence in Barrett's Esophagus.

Introduction. The objective of this study was to evaluate Ki-67 antigen expression in patients with Barrett's esophagus and esophageal adenocarcinoma and to assess its correlation with the metaplasia-esophageal adenocarcinoma progression. Methods. Using immunohistochemistry we evaluated the Ki-67 index in patients with Barrett's esophagus, esophageal adenocarcinoma, and controls. We included patients with endoscopically visible columnar mucosa of the distal esophagus (whose biopsies revealed specialized intestinal-type metaplasia), patients with esophageal and esophagogastric tumors types I and II, and patients with histologically normal gastric mucosa (control). Results. In the 57 patients studied there were no statistically significant differences between the groups with respect to age or race. Patients with cancer were predominantly men. The Ki-67 index averaged 10 ± 4 % in patients with normal gastric mucosa (n = 17), 21 ± 15 % in patients with Barrett's esophagus (n = 21), and 38 ± 16 % in patients with cancer (n = 19). Ki-67 expression was significantly different between all groups (P < 0.05). There was a strong linear correlation between Ki-67 expression and the metaplasia-adenocarcinoma sequence (P < 0.01). In patients with cancer, Ki-67 was not associated with clinical or surgical staging. Conclusions. Ki-67 antigen has increased expression along the metaplasia-adenocarcinoma sequence. There is a strong linear correlation between Ki-67 proliferative activity and Barrett's carcinogenesis.

Effectiveness of risk-reducing salpingo-oophorectomy in preventing ovarian cancer in a high-risk French Canadian population.

BACKGROUND: Women with germ line BRCA1 or BRCA2 mutations have a marked increased risk of breast and ovarian cancer compared with the general population, whereas risk-reducing salpingo-oophorectomy (RRSO) significantly lowers the incidence of these cancers. The objective of this study was to review the clinical and pathological characteristics of a French Canadian population undergoing RRSO. Surgical morbidity was also evaluated. MATERIALS AND METHODS: From December 1999 to December 2009, all women who underwent RRSO at our institution were identified. Medical records were retrospectively reviewed. Descriptive statistics, the Fischer exact test, and the Student t test were used for analysis. RESULTS: During the study period, RRSO was performed on 119 women. Mean age at surgery was 49 years (35-72 years), and 63 patients (53%) were premenopausal. Sixty-two women (52%) had a history of in situ or invasive breast cancer. BRCA1 and BRCA2 mutations were present in 34 patients (29%) and 42 patients (35%), respectively, whereas 43 patients (36%) were considered to have an increased risk of breast and ovarian cancer, despite a personal genetic test, which was either negative (n = 23) or unknown because the patient declined genetic testing (n = 20). Most patients with a uterus in place had a complementary hysterectomy (65%). Six complications occurred (3 hematomas, 2 cardiac arrhythmias, and 1 cystotomy). In one patient (0.8%), a high-grade stage II ovarian cancer was discovered at the time of surgery. Fallopian tube atypias were identified on final pathology in 8 cases (6.7%). After a median follow-up of 22 months, 4 women (3.4%) developed breast cancer and one woman (0.8%) developed peritoneal cancer. CONCLUSIONS: Risk-reducing salpingo-oophorectomy is highly effective in preventing ovarian, fallopian tube, and breast cancers in a high-risk French Canadian population; and the surgical morbidity is low.

Overexpression of NTPDase2 in gliomas promotes systemic inflammation and pulmonary injury.

Gliomas are the most common and devastating type of primary brain tumor. Many non-neoplastic cells, including immune cells, comprise the tumor microenvironment where they create a milieu that appears to dictate cancer development. ATP and the phosphohydrolytic products ADP and adenosine by activating P2 and P1 receptors may participate in these interactions among malignant and immune cells. Purinergic receptor-mediated cell communication is closely regulated by ectonucleotidases, such as by members of the ectonucleoside triphosphate diphosphohydrolase (E-NTPDase) family, which hydrolyze extracellular nucleotides. We have shown that gliomas, unlike astrocytes, exhibit low NTPDase activity. Furthermore, ATP induces glioma cell proliferation and the co-administration of apyrase decreases progression of injected cells in vivo. We have previously shown that NTPDase2 reconstitution dramatically increases tumor growth in vivo. Here we evaluated whether NTPDase2 reconstitution to gliomas modulates systemic inflammatory responses. We observed that NTPDase2 overexpression modulated pro-inflammatory cytokine production and platelet reactivity. Additionally, pathological alterations in the lungs were observed in rats bearing these tumors. Our results suggest that disruption of purinergic signaling via ADP accumulation creates an inflammatory state that may promote tumor spread and dictate clinical progression.

The curry spice curcumin selectively inhibits cancer cells growth in vitro and in preclinical model of glioblastoma.

Previous studies suggested that curcumin is a potential agent against glioblastomas (GBMs). However, the in vivo efficacy of curcumin in gliomas remains not established. In this work, we examined the mechanisms underlying apoptosis, selectivity, efficacy and safety of curcumin from in vitro (U138MG, U87, U373 and C6 cell lines) and in vivo (C6 implants) models of GBM. In vitro, curcumin markedly inhibited proliferation and migration and induced cell death in liquid and soft agar models of GBM growth. Curcumin effects occurred irrespective of the p53 and PTEN mutational status of the cells. Interestingly, curcumin did not affect viability of primary astrocytes, suggesting that curcumin selectivity targeted transformed cells. In U138MG and C6 cells, curcumin decreased the constitutive activation of PI3K/Akt and NFkappaB survival pathways, down-regulated the antiapoptotic NFkappaB-regulated protein bcl-xl and induced mitochondrial dysfunction as a prelude to apoptosis. Cells developed an early G2/M cell cycle arrest followed by sub-G1 apoptosis and apoptotic bodies formation. Caspase-3 activation occurred in the p53-normal cell type C6, but not in the p53-mutant U138MG. Besides its apoptotic effect, curcumin also synergized with the chemotherapeutics cisplatin and doxorubicin to enhance GBM cells death. In C6-implanted rats, intraperitoneal curcumin (50 mg kg(-1) d(-1)) decreased brain tumors in 9/11 (81.8%) animals against 0/11 (0%) in the vehicle-treated group. Importantly, no evidence of tissue (transaminases, creatinine and alkaline phosphatase), metabolic (cholesterol and glucose), oxidative or hematological toxicity was observed. In summary, data presented here suggest curcumin as a potential agent for therapy of GBMs.

Modelo experimental de estenose traqueal mediante ressecção cirúrgica submucosa de anéis traqueais combinada com instilações de hidróxido de sódio / Experimental model of tracheal stenosis with submucosal resection of cartilaginous rings combined with sodium hydroxide instillations

OBJETIVO: Desenvolver, experimentalmente, malácia e estenose traqueal para testar novos modelos de órteses traqueais. MÉTODOS: Ressecamos três anéis cartilaginosos da traqueia cervical de cães no grupo A (n=5) e seis anéis no grupo B (n=4) para produzir malácia. Logo após, a mucosa da região com malácia recebeu aplicações de uma solução de hidróxido de sódio (NaOH) a 23 por cento, e os animais eram acompanhados com exames broncoscópicos para observar o desenvolvimento de estreitamento da luz da via aérea. Quando a estenose era de mais de 50 por cento da luz, ou havia sinais mínimos de insuficiência ventilatória, os animais eram sacrificados. O segmento de via aérea estreitada foi então coletado para análise histológica e era calculada a área de luz residual do segmento traqueal com estenose e malácia. RESULTADOS: Na análise histológica, foi constatada fibrose na submucosa e adventícia, associada a granulomas na mucosa. A luz residual média dos segmentos com estenose foi de 9 por cento e 12 por cento nos grupos A e B, respectivamente, (p>0,05). CONCLUSÃO: A combinação da ressecção de anéis cartilaginosos e da aplicação de NaOH 23 por cento na mucosa respiratória promoveu uma estenose traqueal intensa, porém esteve associada à perda de animais. Novos estudos são necessários para verificar se o emprego isolado de uma das técnicas seria mais seguro e eficaz para desenvolver estenose traqueal.

OBJECTIVE: To experimentally develop tracheal stenosis and malacia to test new models of tracheal stents. METHODS: We resected three cartilaginous rings from the cervical trachea of dogs in group A (n = 5) and six rings in group B (n = 4) to produce malacia. The mucosa of the region with malacia then received applications of a solution of sodium hydroxide (NaOH) at 23 percent, and the animals were accompanied with bronchoscopic examinations to observe the development of luminal narrowing of the airway. When the stenosis was of more than 50 percent or there were minimal signs of ventilatory failure, the animals were sacrificed. The segment of narrowed airway was then collected for histological analysis and calculation of the area of residual lumen in the tracheal segment with stenosis and malacia. RESULTS: In histological analysis, fibrosis was found in the submucosa and adventitia, associated with granulomas in the mucosa. The average residual lumen of the segments with stenosis was 9 percent and 12 percent in groups A and B, respectively (p> 0.05). CONCLUSION: The combination of resection of the cartilaginous rings and the application of 23 percent NaOH in the respiratory mucosa promoted severe tracheal stenosis, but was associated with loss of animals. Further studies are needed to verify that the isolated use of one of the techniques would be safer and more effective to develop tracheal stenosis.

Avaliação da expressão imunoistoquímica da proteína p16INK4a no adenocarcinoma de esôfago / Protein p16INK4a immunohistochemical expression in adenocarcinoma of the esophagus

INTRODUÇÃO: O adenocarcinoma de esôfago apresenta aumento de frequência nas últimas décadas, particularmente em países desenvolvidos. O esôfago de Barrett é reconhecido como a principal lesão precursora e o estudo da sequência metaplasia-displasia-adenocarcinoma mostra a ocorrência de alterações genéticas desde suas fases mais incipientes. As alterações no p16INK4a são relatadas como frequentes no esôfago de Barrett e no carcinoma de esôfago. OBJETIVO: Verificar a prevalência da expressão imunoistoquímica da proteína p16INK4a em exames anatomopatológicos de pacientes com adenocarcinoma de esôfago. MÉTODO: A população do estudo foi constituída de 37 pacientes com adenocarcinoma de esôfago. A expressão da proteína p16 foi detectada por meio de análise imunoistoquímica, com anticorpo primário p16INK4aAb-7, clone 16P07, NeoMarkers e avaliada de acordo com o Sistema de Escore de Imunorreatividade (Immunoreactive scoring system - IRS) modificado. RESULTADOS: No grupo houve predominância de pacientes do sexo masculino (86,5 por cento) e a maioria dos casos correspondia a estádios avançados (III e IV = 67,5 por cento). Em 12 casos (32,4 por cento) foi identificada expressão imunoistoquímica da proteína p16INK4a. Não foi observada relação significativa entre a perda da expressão da proteína p16INK4a e o grau de diferenciação histológica (p=0,81) nem com o estadiamento da doença (p=0,485). CONCLUSÃO: Ocorre perda da expressão imunoistoquímica da proteína p16INK4a, corroborando as informações de que a inativação do gene p16 é um evento frequente e que pode exercer papel importante na carcinogênese do adenocarcinoma de esôfago.

BACKGROUND: The esophageal adenocarcinoma shows an increasing frequence in the last decades, specially in the developed countries. The Barrett´s esophagus is accepted as the major premalignant lesion and the metaplasia-dysplasia-adenocarcinoma sequence presents a lot of genetic changes since its early events. The alterations in p16INK4a are frequent in Barrett´s esophagus and esophageal carcinoma. AIM: To verify the prevalence of the immunohistochemical expression of the p16INK4a protein in patients with esophageal adenocarcinoma. METHODS: The study population consisted of 37 patients with resected esophageal adenocarcinoma. The p16INK4a protein expression was determined by immunohistochemistry using primary antibody p16INK4aAb-7, clone 16P07 NeoMarkers and assessed according to the Immunoreactive scoring system (IRS). RESULTS: Of 37 analyzed patients, the most were male (86,5 percent) and the advanced disease was predominant (stages III and IV = 67,5 percent). In 12 (32,4 percent) the immunohistochemistry was positive for p16INK4a.There was no significative relation between the protein expression and the degrees of histological differentiation of the biopsies and surgical especimens (p=0,81) neither with the staging (p=0,485). CONCLUSION: The lost of the immunohistochemical expression of the p16INK4a protein in this study suggests that p16 is enroled in the carcinogenesis of the adenocarcinoma of esophagus.

Clinical and pathological correlations of C4d immunostaining and its influence on the outcome of kidney transplant recipients.

INTRODUCTION: C4d is a marker of antibody-mediated rejection (ABMR) in kidney allografts, although cellular rejection also have C4d deposits. OBJECTIVE: To correlate C4d expression with clinico-pathological parameters and graft outcomes at three years. METHODS: One hundred forty six renal transplantation recipients with graft biopsies by indication were included. C4d staining was performed by paraffin-immunohistochemistry. Graft function and survival were measured, and predictive variables of the outcome were determined by multivariate Cox regression. RESULTS: C4d staining was detected in 48 (31%) biopsies, of which 23 (14.7%) had diffuse and 25 (16%) focal distribution. Pre-transplantation panel reactive antibodies (%PRA) class I and II were significantly higher in C4d positive patients as compared to those C4d negative. Both glomerulitis and pericapillaritis were associated to C4d (p = 0.002 and p < 0.001, respectively). The presence of C4d in biopsies diagnosed as no rejection (NR), acute cellular rejection (ACR) or interstitial fibrosis/ tubular atrophy (IF/TA) did not impact graft function or survival. Compared to NR, ACR and IF/TA C4d⁻, patients with ABMR C4d⁺ had the worst graft survival over 3 years (p = 0.034), but there was no difference between ABMR versus NR, ACR and IF/TA that were C4d positive (p = 0.10). In Cox regression, graft function at biopsy and high %PRA levels were predictors of graft loss. CONCLUSIONS: This study confirmed that C4d staining in kidney graft biopsies is a clinically useful marker of ABMR, with well defined clinical and pathological correlations. The impact of C4d deposition in other histologic diagnoses deserves further investigation.

Helicobacter pylori eradication in functional dyspepsia: HEROES trial.

BACKGROUND: Eradication of Helicobacter pylori in patients with functional dyspepsia continues to be a matter of debate. We studied eradication effects on symptoms and quality of life of primary care patients. METHODS: Helicobacter pylori -positive adult patients with functional dyspepsia meeting the Rome III International Consensus criteria were randomly assigned to receive omeprazole, amoxicillin trihydrate, and clarithromycin, or omeprazole plus placebo for 10 days. Endoscopy and H pylori tests were performed at screening and at 12 months. Outcome measures were at least 50% symptomatic improvement at 12 months using a validated disease-specific questionnaire (primary end point), patient global assessment of symptoms, and quality of life. RESULTS: We randomly assigned 404 patients (78.7% were women; mean age, 46.1 years); 201 were assigned to be treated with antibiotics (antibiotics group) and 203 to a control group. A total of 389 patients (96.3%) completed the study. The proportion of patients who achieved the primary outcome was 49.0% (94 of 192) in the antibiotics group and 36.5% (72 of 197) in the control group (P = .01; number needed to treat, 8). In the patient global assessment of symptoms, 78.1% in the antibiotics group (157 of 201) answered that they were better symptomatically, and 67.5% in the control group (137 of 203) said that they were better (P = .02). The antibiotics group had a significantly larger increase in their mean (SD) Medical Outcomes Study 36-Item Short Form Health Survey physical component summary scores than the control group did (4.15 [8.5] vs 2.2 [8.1]; P = .02). CONCLUSION: Helicobacter pylori eradication provided significant benefits to primary care patients with functional dyspepsia. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00404534.