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Cancer is a leading cause of death, and the fibrinolytic system shows cooperative effects that facilitate the growth of tumors and the appearance of metastases. This prospective study aimed to evaluate the fibrinolytic potential in cancer patients and its association with mortality outcomes using the fluorometric method of simultaneous thrombin and plasmin generation. The study included 323 cancer patients and 148 healthy individuals. During the 12-month follow-up, 68 patients died. Compared to the control group, cancer patients showed alterations in thrombin production consistent with a hypercoagulability profile, and an increase in plasmin generation. Mortality risk was associated with two parameters of thrombin in both univariate and multivariable analysis: maximum amplitude (Wald 11.78, p < 0.001) and area under the curve (Wald 8.0, p < 0.005), while such associations were not observed for plasmin. In conclusion, this was the first study able to demonstrate the simultaneous evaluation of thrombin and plasmin generation in newly diagnosed untreated cancer patients. Patients with cancer have been observed to exhibit a hypercoagulable profile. During the study, two parameters linked to thrombin generation, MA and AUC, were identified and found to have a potential association with mortality risk. However, no associations were found with parameters related to plasmin generation.

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OBJECTIVE: To analyze the gene and immunohistochemical expression of HIF-1α, GLUT-1, FASN, and adipophilin in normal salivary gland (NSG), pleomorphic adenoma (PA), and carcinoma ex pleomorphic adenoma (CXPA) samples. MATERIAL AND METHODS: The gene expression was investigated by the real-time PCR (qRT-PCR) method in 9 samples of frozen tissues of normal salivary gland, 13 PA, and 10 CXPA. We validated the reactions by immunohistochemistry on 20 samples from NSG, 85 PA, and 44 CXPA. RESULTS: Our results showed that there was no statistically significant difference in HIF-1α gene and immunohistochemistry expression among the tissues studied while FASN gene and immunohistochemistry expression increased along the carcinogenesis of the PA. GLUT-1 was significantly more expressed in tumor tissues (PA and CXPA), although protein is mainly expressed in transformed cells than in PA and NSG. In contrast, adipophilin was significantly more expressed in NSG while the expression of the protein increased in PA and CXPA. CONCLUSIONS: In summary, the data presented here suggest that neoplastic cells reprogram the expression of GLUT-1 and adipophilin to adapt to the tumor microenvironment and reinforce, through immunohistochemical results, a possible transcriptional and post-translational regulatory mechanisms that act on the expression of these genes.

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OBJECTIVE: Tertiary hyperparathyroidism, an autonomous hyperproduction of parathyroid hormone (PTH), has a challenge in its treatment. This study asked whether the intraoperative PTH and calcium drop can confirm the resection of all parathyroid tissues. STUDY DESIGN: Case series with planned data collection. SETTING: Tertiary referral medical center. SUBJECTS AND METHODS: The study assessed patients with tertiary hyperparathyroidism who were treated at the Hospital of the State University of Campinas from 2007 to 2015. All patients underwent total parathyroidectomy with autotransplantation of parathyroid fragments. PTH and calcium were collected during the preoperative period; at 10, 20, and 240 minutes after resection of the glands; and at 1 year after the procedure. Data were analyzed by analysis of variance and logistic regression analysis with statistical values of P < .05. RESULTS: Thirty-five patients were assessed: 17 women (48.57%) and 18 men (51.43%). The percentage of PTH drop was statistically significant at all times, unlike the calcium analysis, but only PTH collected at 20 minutes was able to confirm the removal of all parathyroid tissues (P = .029). Based on the receiver operating characteristic curve, the 71.2% drop obtained high sensitivity and specificity (P = .028). CONCLUSIONS: Treatment success can be predicted by analyzing the decrease of intraoperative PTH and not by calcium. The 71.2% PTH drop at 20 minutes after parathyroidectomy had high sensitivity and specificity to predict surgical cure.

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The proto-oncogene (pleomorphic adenoma gene 1 (PLAG1)) is immunohistochemically overexpressed in pleomorphic adenoma (PA). Its expression in recurrent pleomorphic adenoma (RPA), however, has not been investigated. Since complex mechanisms are involved in tumor recurrence, the aim of this study was to investigate whether PLAG1 overexpression occurs in RPA. We studied PLAG1 protein expression in 40 PAs and 36 RPAs by immunohistochemistry. Cases with immunopositive cells were classified into two categories, between 10 and 50 % and >50 %. In both groups, PLAG1 expression was observed in both epithelial and myoepithelial cells. Of PAs, 37 cases (93 %) were positive, while this was the case in 34 RPA cases (94 %). Our findings suggest that in addition to morphological similarity, PA and RPA express PLAG1, which might play a role in tumor recurrence. Furthermore, as for PA, expression of PLAG1 can be considered a valuable diagnostic marker for RPA.

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PLAG1 (pleomorphic adenoma gene 1) is frequently activated in pleomorphic adenoma (PA). Carcinoma ex pleomorphic adenoma (CXPA) arises in PA, and PLAG1 expression is believed to be maintained from PA to CXPA, as it can contribute to the carcinogenesis process. To evaluate if PLAG1 is a good marker of malignant transformation from PA to CXPA as well as to evaluate if PLAG1 expression is associated with progression and histopathologic subtype of CXPA. Forty PAs, 21 residual PAs (without malignant transformation), and 40 CXPAs were analyzed by immunohistochemistry with PLAG1 antibody. The proportion of positive neoplastic cells was assessed according to a 2-tiered scale: >10% to 50%, and >50% positive cells. The CXPA group was classified according to histopathologic subtype and invasiveness degree. Thirty-seven PAs (92.5%), 15 residual PAs (71%), and 14 CXPAs (35%) were positive for PLAG1. In relation to the CXPA group, among the intracapsular cases, myoepithelial carcinoma and epithelial-myoepithelial carcinoma showed the highest level of PLAG1 expression. PLAG1 expression is lost when PA undergoes malignant transformation, possibly due to other pathway activation and different clone cells. In addition, PLAG1 expression seems to be present mainly in low-grade carcinomas and in cases with early phase of invasion, due to its regulation of oncogene-induced cell senescence. In CXPA, PLAG1 expression was most associated with myoepithelial differentiation. This way, loss of PLAG1 expression can be considered a hallmark of CXPA carcinogenesis, mainly when there is only epithelial differentiation.

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Carcinoma ex pleomorphic adenoma (CXPA) has been considered an interesting model of carcinogenesis, presenting various histological subtypes and invasiveness phase. The objective was to determine the proliferative index of CXPA and comparing to pleomorphic adenoma (PA). Thirty six cases of CXPA (36 PA) and 22 areas of PA in CXPA (residual PA) were studied by Ki-67 expression. All CXPA cases were classified according to invasiveness phase (intracapsular, minimally and frankly invasive) and histopathological subtypes. Data was statistically analyzed by Wilcoxon, Mann-Whitney and Kruskal-Wallis tests. CXPA included 5 intracapsular, 9 minimally invasive and 22 frankly invasive cases. Fifteen cases corresponded to salivary duct carcinoma, 7 to adenocarcinoma NOS, 7 myoepithelial, 5 epithelial-myoepithelial, one case of squamous cell and one case of sarcomatoid carcinoma. The Ki-67 index of PA and residual PA were significantly lower than CXPA. Intracapsular and minimally invasive showed smaller proliferative index than frankly invasive. Considering the subtypes of CXPA, there was not a statistic difference among them. Ki-67 is a useful marker in the differential diagnosis of PA and CXPA, even when in the early invasive phase.

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Carcinoma ex pleomorphic adenoma (CXPA) has been considered an interesting model of carcinogenesis, presenting various histological subtypes and invasiveness phase. The objective was to determine the proliferative index of CXPA and comparing to pleomorphic adenoma (PA). Thirty six cases of CXPA (36 PA) and 22 areas of PA in CXPA (residual PA) were studied by Ki-67 expression. All CXPA cases were classified according to invasiveness phase (intracapsular, minimally and frankly invasive) and histopathological subtypes. Data was statistically analyzed by Wilcoxon, Mann-Whitney and Kruskal-Wallis tests. CXPA included 5 intracapsular, 9 minimally invasive and 22 frankly invasive cases. Fifteen cases corresponded to salivary duct carcinoma, 7 to adenocarcinoma NOS, 7 myoepithelial, 5 epithelial-myoepithelial, one case of squamous cell and one case of sarcomatoid carcinoma. The Ki-67 index of PA and residual PA were significantly lower than CXPA. Intracapsular and minimally invasive showed smaller proliferative index than frankly invasive. Considering the subtypes of CXPA, there was not a statistic difference among them. Ki-67 is a useful marker in the differential diagnosis of PA and CXPA, even when in the early invasive phase.

Carcinoma ex adenoma pleomorfo (CXAP) tem sido considerado um interessante modelo de carcinogênese, apresentando vários subtipos histológicos e fases de invasividade. Determinar o índice proliferativo de CXAP e compará-lo ao adenoma pleomorfo (AP). e seis casos de CXAP, 36 AP, e 22 áreas de AP em CXAP (AP residual) foram estudadas através da expressão de Ki-67. Todos os casos de CXAP foram classificados de acordo com a fase de invasividade (intracapsular, minimamente invasivo e francamente invasivo) e de acordo com os diversos subtipos histopatológicos. Os dados foram estatisticamente analisados através dos testes Wilcoxon, Mann-Whitney e Kruskal-Wallis. O grupo de CXAP era formado por 5 intracapsulares, 9 minimamente invasivos e 22 francamente invasivos. Quinze casos corresponderam a carcinoma de ducto salivar, 7 a adenocarcinoma nos, 7 a carcinoma mioepitelial, 5 a carcinoma epitelial-mioepitelial, 1 a carcinoma epidermoide e 1 a carcinoma sarcomatóide. Os índices de Ki-67 de AP e AP residual foram significativamente menores que o encontrado em CXAP. Os casos intracapsulares e minimamente invasivos mostraram índices proliferativos menores que os francamente invasivos. Considerando os subtipos histológicos de CXAP, não houve diferença estatística entre eles. Ki-67 é um marcador útil no diagnóstico diferencial de AP e CXAP, mesmo quando o carcinoma está em fase precoce de invasividade.

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Context. The possibility of cephalic venous hypertension with the resultant facial edema and elevated cerebrospinal fluid pressure continues to challenge head and neck surgeons who perform bilateral radical neck dissections during simultaneous or staged procedures. Case Report. The staged procedure in patients who require bilateral neck dissections allows collateral venous drainage to develop, mainly through the internal and external vertebral plexuses, thereby minimizing the risks of deleterious consequences. Nevertheless, this procedure has disadvantages, such as a delay in definitive therapy, the need for a second hospitalization and anesthesia, and the risk of cutting lymphatic vessels and spreading viable cancer cells. In this paper, we discuss the rationale and feasibility of preserving the external jugular vein. Considering the limited number of similar reports in the literature, two cases in which this procedure was accomplished are described. The relevant anatomy and technique are reviewed and the patients' outcomes are discussed. Conclusion. Preservation of the EJV during bilateral neck dissections is technically feasible, fast, and safe, with clinically and radiologically demonstrated patency.

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AIMS: Metastasizing pleomorphic adenoma (MPA) is a rare tumour, and its mechanism of metastasis still is unknown. To date, there has been no study on MPA genomics. We analysed primary and secondary MPAs with array comparative genomic hybridization to identify somatic copy number alterations and affected genes. METHODS AND RESULTS: Tumour DNA samples from primary (parotid salivary gland) and secondary (scalp skin) MPAs were subjected to array comparative genomic hybridization investigation, and the data were analysed with NEXUS COPY NUMBER DISCOVERY. The primary MPA showed copy number losses affecting 3p22.2p14.3 and 19p13.3p123, and a complex pattern of four different deletions at chromosome 6. The 3p deletion encompassed several genes: CTNNB1, SETD2, BAP1, and PBRM1, among others. The secondary MPA showed a genomic profile similar to that of the primary MPA, with acquisition of additional copy number changes affecting 9p24.3p13.1 (loss), 19q11q13.43 (gain), and 22q11.1q13.33 (gain). CONCLUSION: Our findings indicated a clonal origin of the secondary MPA, as both tumours shared a common profile of genomic copy number alterations. Furthermore, we were able to detect in the primary tumour a specific pattern of copy number alterations that could explain the metastasizing characteristic, whereas the secondary MPA showed a more unbalanced genome.

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CONTEXT AND OBJECTIVE: Carotid body tumors, or chemodectomas, are the most common head and neck paragangliomas, accounting for 80% of the cases. They may present minor symptoms; however, they deserve special attention in order to achieve accurate diagnosis and adequate treatment. The objectives of this study were to show the approach towards chemodectomas and evaluate the complications of the patients treated surgically without previous embolization. DESIGN AND SETTING: Retrospective study on chemodectomas followed up at the Head and Neck Surgery Service, Department of Surgery, Unicamp. METHODS: Twenty-two patients were evaluated between 1983 and 2009. The diagnosis was based on clinical findings and imaging methods. The epidemiological characteristics, lesion characteristics, diagnostic methods, treatment and complications were analyzed. RESULTS: The paragangliomas were classified as Shamblin I (9%), II (68.1%) and III (22.7%). Angiography, magnetic resonance imaging and computed tomography confirmed the diagnosis in 20 patients (90.9%). Five (22.7%) had significant bleeding during the surgery, while four (18.1%) had minor bleeding. Four patients (18.1%) developed neurological sequelae. Seven (31.8%) needed ligatures of the external carotid artery. Three patients (13.6%) underwent carotid bulb resection. The postoperative follow-up ranged from 3 months to 14 years without recurrences or mortality. CONCLUSIONS: In our experience and in accordance with the literature, significant bleeding and neurological sequelae may occur in chemodectoma cases, particularly in Shamblin III patients. The complications from treatment without previous embolization were similar to data in the literature data, from cases in which this procedure was applied prior to surgery.

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