First Use of AXL Targeting in Metastatic, Refractory, Adenoid Cystic Carcinoma: A Case Report.

First use of AXL-targeting in adenoid cystic carcinoma (ACC); with positive results, ACC now included in AXL studies.

Hepatobiliary phases in magnetic resonance imaging using liver-specific contrast for focal lesions in clinical practice.

BACKGROUND: Challenging lesions, difficult to diagnose through non-invasive methods, constitute an important emotional burden for each patient regarding a still uncertain diagnosis (malignant x benign). In addition, from a therapeutic and prognostic point of view, delay in a definitive diagnosis can lead to worse outcomes. One of the main innovative trends currently is the use of molecular and functional methods to diagnosis. Numerous liver-specific contrast agents have been developed and studied in recent years to improve the performance of liver magnetic resonance imaging (MRI). More recently, one of the contrast agents introduced in clinical practice is gadoxetic acid (gadoxetate disodium). AIM: To demonstrate the value of the hepatobiliary phases using gadoxetic acid in MRI for the characterization of focal liver lesions (FLL) in clinical practice. METHODS: Overall, 302 Lesions were studied in 136 patients who underwent MRI exams using gadoxetic acid for the assessment of FLL. Two radiologists independently reviewed the MRI exams using four stages, and categorized them on a 6-point scale, from 0 (lesion not detected) to 5 (definitely malignant). The stages were: stage 1- images without contrast, stage 2- addition of dynamic phases after contrast (analogous to usual extracellular contrasts), stage 3- addition of hepatobiliary phase after 10 min (HBP 10'), stage 4- hepatobiliary phase after 20 min (HBP 20') in addition to stage 2. RESULTS: The interobserver agreement was high (weighted Kappa coefficient: 0.81- 1) at all stages in the characterization of benign and malignant FLL. The diagnostic weighted accuracy (Az) was 0.80 in stage 1 and was increased to 0.90 in stage 2. Addition of the hepatobiliary phase increased Az to 0.98 in stage 3, which was also 0.98 in stage 4. CONCLUSION: The hepatobiliary sequences improve diagnostic accuracy. With growing potential in the era of precision medicine, the improvement and dissemination of the method among medical specialties can bring benefits in the management of patients with FLL that are difficult to diagnose.

Lack of adequate predialyis care and previous hemodialysis, but not hemoglobin variability, are independent predictors of anemia-associated mortality in incident Brazilian peritoneal dialysis patients: results from the BRAZPD study.

BACKGROUND/AIMS: The objective of this study was to analyze the prevalence of anemia and variability of hemoglobin (Hb) values in peritoneal dialysis (PD) patients, to establish its associated factors and their impact on clinical outcomes in a large cohort of patients starting PD treatment. METHODS: Data were collected monthly in incident patients, who were followed until the primary endpoint (death from all causes) or until leaving the study. RESULTS: 2,156 patients starting PD were included. The prevalence of Hb lower than 11 g/dl was 57% at baseline and decreased to 38% at the 4th month. Lack of adequate predialysis care and previous treatment with hemodialysis were the most important factors associated with anemia. Anemia was an independent predictor of mortality. There were no differences in patient survival throughout the different groups of Hb variability. CONCLUSION: Our data point to the need of identifying other risk factors for anemia and aggressively interfere with the modifiable ones in order to correct anemia and decrease mortality in this group of high-risk patients.

Effect of anti-TNF-α on peritoneal endometrial implants of rats.

OBJECTIVE: To evaluate the effect of anti-TNF-α in the treatment of endometrial implants in the peritoneum of rats. METHODS: Endometrial implants were surgically induced in 120 female Wistar-Albino rats. The animals were randomly divided into four groups. Group C (n = 36) received an intraperitoneal injection of 0.2 ml of saline. Group L (n = 41) received a subcutaneous injection of 1mg/kg of leuprolide. Group I5 (n = 20) received a subcutaneous injection of 5mg/kg of monoclonal anti-tumor necrosis factor (TNF) a (infliximab). Group I10 (n = 20) received a subcutaneous injection of 10mg/kg of infliximab. The rats were sacrificed after 21 days to assess the size of the implants and the expression of TNF. RESULTS: Treatment with leuprolide (group L) promoted an absolute reduction in the surface area of the implant when compared with group C (+14 mm vs. 0mm, p = 0.013) and group I10 (+14 mm vs. +5 Mm, p = 0.018). Likewise, a percentage reduction of surface area of the implant was observed comparing group L with group C (+33.3% vs. 0%, p = 0.005) and group I10 (+33.3% vs. +18.3%, p = 0.027). Treatment with infliximab was not able to decrease the surface area of the implants when compared with group C. The expression of TNF-α in groups L, I5 and I10 was lower than in group C (505.6 mm(2) vs. 660.5 mm(2) vs. 317.2 mm(2) vs. 2519.3 mm(2), respectively; p <0.001). CONCLUSION: The anti-TNF-α therapy reduced the expression of TNF-α in endometriotic implants, but did not reduce the surface area of the lesion.

Efeito do anti-TNF-α em implantes endometriais no peritônio de ratas / Effect of anti-TNF-α on peritoneal endometrial implants of rats

OBJETIVO: Avaliar o efeito da terapia anti-TNF-α no tratamento de implantes endometriais no peritônio de ratas. MÉTODOS: Os implantes endometrióticos foram induzidos cirurgicamente em 120 ratas Wistar-Albino. Os animais foram aleatoriamente distribuídos em 4 grupos. O grupo C (n=36) recebeu uma injeção intraperitoneal de 0,2ml de solução salina. O grupo L (n=41) recebeu uma injeção subcutânea de 1mg/kg de leuprolide. O grupo I5 (n=20) recebeu uma injeção subcutânea de 5mg/kg de anticorpo monoclonal anti-fator de necrose tumoral (TNF) a (infliximab). O grupo I10 (n=20) recebeu uma injeção subcutânea de 10mg/kg de infliximab. As ratas foram sacrificadas após 21 dias para se avaliar o tamanho dos implantes e a expressão do TNF-α. RESULTADOS: O tratamento com leuprolide promoveu uma redução absoluta na área de superfície do implante comparado com o grupo C (+14mm vs. 0mm; p=0,013) e com o grupo I10 (+14mm vs. +5mm; p=0,018). Da mesma forma, uma redução percentual da area de superfície do implante foi observada comparando o grupo L com o grupo C (+33,3 por cento vs. 0 por cento; p=0,005) e com o grupo I10 (+33,3 por cento vs. +18,3 por cento; p=0,027). O tratamento com infliximab não foi capaz de diminuir a área de superfície do implante comparado com o grupo C. A expressão de TNF-α reduziu nos grupos L, I5 e I10 comparado com o grupo C (505,6µm² vs. 660,5µm² vs. 317,2µm² vs. 2519,3µm², respectivamente; p<0,001). CONCLUSÃO: A terapia anti-TNF-α reduziu a expressão de TNF-α nos implantes endometrióticos mas não reduziu a área de superfície da lesão.

OBJECTIVE: To evaluate the effect of anti-TNF-α in the treatment of endometrial implants in the peritoneum of rats. METHODS: Endometrial implants were surgically induced in 120 female Wistar-Albino rats. The animals were randomly divided into four groups. Group C (n = 36) received an intraperitoneal injection of 0.2 ml of saline. Group L (n = 41) received a subcutaneous injection of 1mg/kg of leuprolide. Group I5 (n = 20) received a subcutaneous injection of 5mg/kg of monoclonal anti-tumor necrosis factor (TNF) a (infliximab). Group I10 (n = 20) received a subcutaneous injection of 10mg/kg of infliximab. The rats were sacrificed after 21 days to assess the size of the implants and the expression of TNF. RESULTS: Treatment with leuprolide (group L) promoted an absolute reduction in the surface area of the implant when compared with group C (+14 mm vs. 0mm, p = 0.013) and group I10 (+14 mm vs. +5 Mm, p = 0.018). Likewise, a percentage reduction of surface area of the implant was observed comparing group L with group C (+33.3 percent vs. 0 percent, p = 0.005) and group I10 (+33.3 percent vs. +18.3 percent, p = 0.027). Treatment with infliximab was not able to decrease the surface area of the implants when compared with group C. The expression of TNF-α in groups L, I5 and I10 was lower than in group C (505.6 mm² vs. 660.5 mm² vs. 317.2 mm² vs. 2519.3 mm², respectively; p <0.001). CONCLUSION: The anti-TNF-α therapy reduced the expression of TNF-α in endometriotic implants, but did not reduce the surface area of the lesion.

Effect of the bone marrow derived-mononuclear stem cells transplantation in the growth, VEGF-R and TNF-alpha expression of endometrial implants in Wistar rats.

OBJECTIVE: To study the effect of bone marrow derived-mononuclear stem cells transplantation in the growth, VEGF-R and TNF-alpha expression of surgically induced endometriosis in an experimental model. STUDY DESIGN: This is an experimental study conducted in the Center for Health and Biological Sciences at the Pontifical Catholic University of Parana, Brazil. Endometriotic implants were surgically induced in 120 female Wistar rats. The animals with viable endometrial implant (larger than 25 mm(2)) were randomically divided into 3 groups to receive an intraperitoneal injection of 0.2 cc of saline solution (C group; n=30), a subcutaneous injection of 1mg/kg of leuprolide (L group; n=34), or an intraperitoneal injection of 5×10(6) bone marrow derived-mononuclear stem cells (SC group; n=36). They were sacrificed after 21 days to assess the implants' size and the tissue expression of vascular endothelial growth factor receptor (VEGF-R) and tumor necrosis factor-alpha (TNF-alpha). RESULTS: Treatment with leuprolide decreased the surface area of the endometriotic implant compared to the SC group and the C group. The absolute reduction in the surface area of the implant was 16.5mm, 0mm, and 0mm (p=0.007), respectively, and the percent reduction was 40.2%, 0%, and 0% (p=0.001). VEGF-R expression in the endometriotic implant decreased after treatment in the L and SC groups compared to the C group (409.6 µm(2) vs. 465 µm(2) vs. 920.9 µm(2), respectively; p=0.021). TNF-alpha expression also reduced in the L and SC groups compared to the C group (585.7 µm(2) vs. 549.3 µm(2) vs. 2402.1 µm(2), respectively; p<0.001). CONCLUSION: Bone marrow derived-mononuclear stem cells transplantation decreased the expression of VEGF-R and TNF-alpha in the endometriotic implant but did not reduce the surface area of the lesion.

Desenvolvimento de modelo experimental de endometriose em ratas / Development of an experimental model of endometriosis in rats

OBJETIVO: Desenvolver um modelo de endometriose experimental em ratas. MÉTODOS: Foram utilizadas 30 ratas adultas da linhagem Wistar. A técnica cirúrgica consistiu em laparotomia mediana com identificação do útero bicorno e ressecção de um segmento de 2 cm do corno uterino direito. Um retalho de 0,25 cm² foi retirado dessa estrutura e suturado na parede abdominal com a face endometrial voltada para a cavidade peritoneal. As ratas foram divididas aleatoriamente em dois grupos de acordo com o tempo para a reoperação: grupo 1 (n=15), reoperado em 30 dias, e grupo 2 (n=15), em 60 dias. No momento da segunda laparotomia os implantes foram avaliados macroscopicamente, ressecados e encaminhados para análise microscópica com coloração hematoxilina-eosina e imunohistoquímica (HEMA, AE1 e AE2). RESULTADOS: Os implantes se desenvolveram em 83,3 por cento do Grupo 1 e 71,4 por cento no Grupo 2. Não houve diferença estatisticamente significativa entre o peso dos animals dos dois grupos. Também não houve diferença estatisticamente significativa no tamanho da área das lesões induzidas: no Grupo 1 a média foi 0,37 cm² e no Grupo 2, de 0,25 cm². Segundo a classificação histológica semi-quantitativa de Keenan (de acordo com a preservação da camada epitelial de endométrio), o Grupo 1 teve média de 1,9 e o Grupo 2, de 2,4. CONCLUSÃO: A técnica utilizada para o desenvolvimento de endometriose em ratas foi satisfatória.

OBJECTIVES: To develop an experimental model of endometriosis in rats. METHODS: Thirty adult female Wistar rats were used. The surgical technique consisted of median laparotomy with identification of the bicornuate uterus and resection of a 2-cm segment of the right uterine horn. A 0.25 cm² flap was removed from that structure and sutured to the abdominal wall with the endometrial side facing the peritoneal cavity. The rats were randomly divided into two groups according to the reoperation date: group 1 (n=15) was reoperated in 30 days, and group 2 (n=15), in 60 days. On the occasion of the second laparotomy, the implants were evaluated macroscopically, resected and referred for microscopic analysis with hematoxylin-eosin and immunohistochemical staining (HEMA, AE1 and AE2). RESULTS: The implants developed in 83.3 percent of group 1 and 71.4 percent of group 2. There was no statistically significant difference between the weights of the animals in the two groups. No statistically significant difference was found in the surface area of the induced lesions: in group 1, the mean was 0.37 cm² and in group 2, 0.25 cm². According to Keenan's semiquantitative histological classification (based on the preservation status of the epithelial layer of the endometrium), the mean for group 1 was 1.9 and for group 2, 2.4. CONCLUSION: The technique used for inducing the development of endometriosis in rats was satisfactory.

Development of an experimental model of endometriosis in rats.

OBJECTIVES: To develop an experimental model of endometriosis in rats. METHODS: Thirty adult female Wistar rats were used. The surgical technique consisted of median laparotomy with identification of the bicornuate uterus and resection of a 2-cm segment of the right uterine horn. A 0.25 cm(2) flap was removed from that structure and sutured to the abdominal wall with the endometrial side facing the peritoneal cavity. The rats were randomly divided into two groups according to the reoperation date: group 1 (n=15) was reoperated in 30 days, and group 2 (n=15), in 60 days. On the occasion of the second laparotomy, the implants were evaluated macroscopically, resected and referred for microscopic analysis with hematoxylin-eosin and immunohistochemical staining (HEMA, AE1 and AE2). RESULTS: The implants developed in 83.3 % of group 1 and 71.4% of group 2. There was no statistically significant difference between the weights of the animals in the two groups. No statistically significant difference was found in the surface area of the induced lesions: in group 1, the mean was 0.37 cm(2) and in group 2, 0.25 cm(2). According to Keenan's semiquantitative histological classification (based on the preservation status of the epithelial layer of the endometrium), the mean for group 1 was 1.9 and for group 2, 2.4. CONCLUSION: The technique used for inducing the development of endometriosis in rats was satisfactory.