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Objectives: To investigate visual and anatomical outcomes of vitreoretinal surgeries in patients with Eales' disease. Materials and Methods: In this retrospective study, 22 eyes of 21 patients with vitreous hemorrhage (VH) or tractional retinal detachment (TRD) secondary to Eales' disease who underwent vitreoretinal surgery between January 1997 and December 2015 and had at least 1 year of follow-up were included. Results: The mean best corrected visual acuity (BCVA) was significantly higher at final visit (0.6±0.9 logMAR) than the preoperative values (1.8±1.1 logMAR) (p<0.001). After surgery, BCVA was stable in 4 eyes (18.2%), increased in 16 eyes (72.7%), and decreased in 2 eyes (9.1%). Although the mean BCVA was better in the VH group (0.3±0.34 logMAR) than the TRD group (0.9±1.1 logMAR), the difference was not statistically significant (p=0.1). Multivariable linear regression analyses revealed that final BCVA was negatively associated with preoperative or postoperative proliferative vitreoretinopathy grade C (PVR-C), preoperative retinal detachment involving the macula, postoperative neovascular glaucoma, and long preoperative duration of disease, and positively associated with preoperative BCVA. Final BCVA was not associated with preoperative retinal and disc neovascularization, rubeosis iridis, total posterior hyaloid detachment, preoperative retinal laser photocoagulation, indication of surgery, diameter of sclerotomy (20 or 23 gauge), preoperative lens status, preoperative or postoperative epimacular membrane, peroperative iatrogenic retinal breaks, postoperative hypotony, cystoid macular edema, and new or recurrent retinal detachment. The primary anatomic success rate was 81.8% and the final anatomic success rate was 90.9%. Conclusion: In Eales' disease, good visual results can be obtained with vitreoretinal surgery if the detachment area does not involve the macula and PVR-C does not develop pre- or postoperatively.
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Neovascularización Patológica/complicaciones , Desprendimiento de Retina/cirugía , Vasculitis Retiniana/complicaciones , Agudeza Visual , Vitrectomía/métodos , Hemorragia Vítrea/cirugía , Adulto , Anciano , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Neovascularización Patológica/cirugía , Desprendimiento de Retina/etiología , Vasculitis Retiniana/cirugía , Estudios Retrospectivos , Factores de Tiempo , Resultado del Tratamiento , Hemorragia Vítrea/etiología , Adulto JovenRESUMEN
Background Macrotrabecular-massive (MTM) subtype and vessels encapsulating tumor clusters (VETC) pattern of hepatocellular carcinoma (HCC) are associated with unfavorable prognosis. Purpose To estimate the potential of preoperative CT in the prediction of MTM subtype and VETC pattern. Materials and Methods Patients who underwent surgical resection or liver transplant and preoperative CT for HCC between January 2015 and June 2018 were retrospectively included in the primary cohort. CT imaging features were evaluated by two radiologists. Predictors associated with the MTM subtype or VETC pattern were determined by using logistic regression analyses and the performance was tested in a validation cohort. Prognostic factors associated with early recurrence after surgical resection were identified by using Cox regression analyses. Results The primary cohort included 170 patients (median age, 55 years; interquartile range, 48-63 years; 152 men). Serum α-fetoprotein level higher than 100 ng/mL (odds ratio [OR], 4.3; 95% CI: 2.1, 9.2; P < .001), intratumor necrosis (OR, 5.2; 95% CI: 2.5, 11.0; P < .001), and intratumor hemorrhage (OR, 5.4; 95% CI: 1.3, 23.3; P = .02) were independent predictors for MTM subtype, whereas tumor size greater than 5 cm (OR, 3.8; 95% CI: 1.7, 8.1; P = .001) and intratumor necrosis (OR, 2.1; 95% CI: 1.0, 4.4; P = .045) were independent predictors for VETC pattern. These features were used for the construction of ANH and SN scores (where A is α-fetoprotein level, N is necrosis, H is hemorrhage, and S is size), respectively, which showed comparable prediction performance in the primary and validation cohorts. Preoperative high ANH and high SN phenotype (hazard ratio, 1.9; 95% CI: 1.2, 3.0; P = .01) was independently associated with early recurrence after surgical resection. Conclusion Preoperative CT features could be used for the characterization of macrotrabecular-massive subtype and vessels that encapsulate tumor clusters pattern and were of prognostic significance for early recurrence in patients with hepatocellular carcinoma. Online supplemental material is available for this article. See also the editorial by Yoon and Kim in this issue. Published under a CC BY 4.0 license.
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Carcinoma Hepatocelular/diagnóstico por imagen , Neoplasias Hepáticas/diagnóstico por imagen , Neovascularización Patológica/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Biomarcadores de Tumor/sangre , Carcinoma Hepatocelular/cirugía , China , Femenino , Humanos , Neoplasias Hepáticas/cirugía , Masculino , Persona de Mediana Edad , Neovascularización Patológica/cirugía , Periodo Preoperatorio , Pronóstico , Estudios Retrospectivos , Carga TumoralRESUMEN
PURPOSE: Itraconazole has been repurposed as an anticancer therapeutic agent for multiple malignancies. In preclinical models, itraconazole has antiangiogenic properties and inhibits Hedgehog pathway activity. We performed a window-of-opportunity trial to determine the biologic effects of itraconazole in human patients. EXPERIMENTAL DESIGN: Patients with non-small cell lung cancer (NSCLC) who had planned for surgical resection were administered with itraconazole 300 mg orally twice daily for 10-14 days. Patients underwent dynamic contrast-enhanced MRI and plasma collection for pharmacokinetic and pharmacodynamic analyses. Tissues from pretreatment biopsy, surgical resection, and skin biopsies were analyzed for itraconazole and hydroxyitraconazole concentration, and vascular and Hedgehog pathway biomarkers. RESULTS: Thirteen patients were enrolled in this study. Itraconazole was well-tolerated. Steady-state plasma concentrations of itraconazole and hydroxyitraconazole demonstrated a 6-fold difference across patients. Tumor itraconazole concentrations trended with and exceeded those of plasma. Greater itraconazole levels were significantly and meaningfully associated with reduction in tumor volume (Spearman correlation, -0.71; P = 0.05) and tumor perfusion (Ktrans; Spearman correlation, -0.71; P = 0.01), decrease in the proangiogenic cytokines IL1b (Spearman correlation, -0.73; P = 0.01) and GM-CSF (Spearman correlation, -1.00; P < 0.001), and reduction in tumor microvessel density (Spearman correlation, -0.69; P = 0.03). Itraconazole-treated tumors also demonstrated distinct metabolic profiles. Itraconazole treatment did not alter transcription of GLI1 and PTCH1 mRNA. Patient size, renal function, and hepatic function did not predict itraconazole concentrations. CONCLUSIONS: Itraconazole demonstrates concentration-dependent early antivascular, metabolic, and antitumor effects in patients with NSCLC. As the number of fixed dose cancer therapies increases, attention to interpatient pharmacokinetics and pharmacodynamics differences may be warranted.
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Inhibidores de la Angiogénesis/administración & dosificación , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Itraconazol/administración & dosificación , Neovascularización Patológica/tratamiento farmacológico , Adulto , Inhibidores de la Angiogénesis/efectos adversos , Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Biopsia , Carcinoma de Pulmón de Células no Pequeñas/sangre , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico por imagen , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Femenino , Proteínas Hedgehog/genética , Humanos , Itraconazol/análogos & derivados , Itraconazol/sangre , Itraconazol/farmacocinética , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Neovascularización Patológica/sangre , Neovascularización Patológica/diagnóstico por imagen , Neovascularización Patológica/cirugía , Receptor Patched-1/genética , Proteína con Dedos de Zinc GLI1/genéticaRESUMEN
BACKGROUND: To explore the correlation of flash dual source computed tomography perfusion imaging (CTPI) and regional lymph node metastasis of non-small cell lung cancer (NSCLC), and to evaluate the value of CT perfusion parameters in predicting regional lymph node metastasis of NSCLC. METHODS: 120 consecutive patients with NSCLC confirmed by postoperative histopathology were underwent flash dual source CT perfusion imaging in pre-operation. The CT perfusion parameters of NSCLC, such as blood flow (BF), blood volume (BV), mean transit time (MTT) and permeability (PMB) were obtained by the image post-processing. Then microvessel density (MVD), luminal vascular number (LVN), luminal vascular area (LVA) and luminal vascular perimeter (LVP) of NSCLC were counted by immunohistochemistry. These cases were divided into group A (patients with lymph node metastasis, 58 cases) and group B (patients without lymph node metastasis, 62 cases) according to their pathological results. The CT perfusion parameters and the microvessel parameters were contrastively analysed between the two groups. Receiver operating characteristic (ROC) curve was used to assess the diagnostic efficiency of CT perfusion parameters in predicting regional lymph node metastasis of NSCLC in pre-operation. RESULTS: Group A presented significantly lower LVA, BF and higher MTT, PMB than Group B (P < 0.05), while BV, LVN, LVP and MVD were no significant difference (P > 0.05). Correlation analysis showed that BF was correlated with LVA and LVP (P < 0.05), while BV, MTT and PMB were not correlated with LVN, LVA and LVP (P > 0.05). All the perfusion parameters were not correlated with MVD. According to the ROC curve analysis, when BF < 85.16 ml/100 ml/min as a cutoff point to predict regional lymph node metastasis of NSCLC, the sensitivity, specificity, accuracy, positive predictive value and negative predictive value were 60.8, 81.7, 71.5, 75.6 and 69.5% respectively. CONCLUSION: Flash dual source CT perfusion imaging can non-invasively indicate the luminal vascular structure of tumor and BF can be used as one of the important indexes in predicting regional lymph node metastasis of NSCLC in pre-operation.
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Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/patología , Metástasis Linfática/diagnóstico , Neovascularización Patológica/diagnóstico por imagen , Imagen de Perfusión , Tomografía Computarizada por Rayos X , Adulto , Anciano , Carcinoma de Pulmón de Células no Pequeñas/irrigación sanguínea , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Correlación de Datos , Estudios de Factibilidad , Femenino , Humanos , Pulmón/irrigación sanguínea , Pulmón/diagnóstico por imagen , Pulmón/patología , Neoplasias Pulmonares/irrigación sanguínea , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/cirugía , Ganglios Linfáticos/patología , Ganglios Linfáticos/cirugía , Metástasis Linfática/patología , Masculino , Microvasos/diagnóstico por imagen , Persona de Mediana Edad , Estadificación de Neoplasias , Neovascularización Patológica/patología , Neovascularización Patológica/cirugía , Valor Predictivo de las Pruebas , Periodo PreoperatorioRESUMEN
BACKGROUND: Colorectal cancer (CRC) is an important current problem concerning public health due to its high incidence and mortality. Advances in molecular and cellular knowledge and the detection of new disease biomarkers are very important to improve prognosis, prediction, and early diagnosis. In this study, we aimed to analyze the gene and protein expression levels of two angiogenic markers, VEGF and soluble Endoglin, during different tumor stages as well as at different stages of cancer treatment, to predict the diagnosis and evolution of colon and rectal cancer. MATERIAL AND METHODS: This study includes 133 CRC patients (93 with colon cancer and 40 with rectal cancer) on which the gene and protein expression of Endoglin (membrane and soluble form) and VEGF were analyzed by molecular and immunohistochemical techniques on different tumor stage samples and plasma obtained preoperatively as well as 3, 6, and 9 months after resection of the tumor. RESULTS: VEGF and Endoglin gene expressions were higher in tumor tissue than in surrounding non-tumoral tissue for both types of cancer. The VEGF levels in plasma were found to decrease in less aggressive tumors, whereas soluble Endoglin was increased in preoperative samples of patients with metastasis. Membrane Endoglin expression was higher on the vascular endothelium of more aggressive tumors. In contrast, Endoglin expression was mainly in the colon epithelium in less aggressive stage tumors. CONCLUSION: Endoglin and VEGF are proteins with a major role in the tumor angiogenesis process. This study performed with a wide cohort of human samples shows that both proteins seem to be valuable biomarkers in the diagnosis and prognosis of CRC.
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Biomarcadores de Tumor/sangre , Neoplasias del Colon/diagnóstico , Endoglina/sangre , Neovascularización Patológica/diagnóstico , Neoplasias del Recto/diagnóstico , Factor A de Crecimiento Endotelial Vascular/sangre , Anciano , Biomarcadores de Tumor/metabolismo , Colectomía , Colon/patología , Colon/cirugía , Neoplasias del Colon/sangre , Neoplasias del Colon/patología , Neoplasias del Colon/cirugía , Endoglina/metabolismo , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Neovascularización Patológica/sangre , Neovascularización Patológica/patología , Neovascularización Patológica/cirugía , Proctectomía , Pronóstico , Estudios Prospectivos , Neoplasias del Recto/sangre , Neoplasias del Recto/patología , Neoplasias del Recto/cirugía , Recto/patología , Recto/cirugía , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
OBJECTIVE: Meningioma is an extra-axial tumor that forms adhesions toward the brain surface in the course of its growth. Predicting adhesions between the tumor and the brain surface leads to better predictions of surgical results. There are few studies on brain-tumor adhesions or postoperative hemorrhage. This study aimed to assess tumor vascularity of the dura and cerebral surface, and predict surgical outcomes using four-dimensional computed tomography angiography (4D CTA). PATIENTS AND METHODS: Using a dynamic contrast CT, we conducted a retrospective study of 27 patients with convexity (n = 15), falx (n = 6), and parasagittal (n = 6) meningiomas treated in our hospital from January 2016 to September 2018. We set the region of interest on the dural layer and cerebral surface side of meningiomas and calculated the mean CT value in each region. Distribution of blood flow in the tumor was classified into two groups: A, which has a higher CT value of the dural side than that of the brain surface side at every timing, and B, which meets the criteria other than those in group A. Demographic data, preoperative characteristic images, and postoperative complications were compared between the groups. RESULTS: Twelve and 15 patients were classified into groups A and B, respectively. The extent of adhesions against the cerebral cortex in group A was significantly less severe compared with that in group B (p = 0.038). The rate of postoperative hemorrhage occurrence in group B (53%) was significantly higher than that in group A (8%) (p = 0.04). There were no significant differences in the other preoperative characteristic images or perioperative parameters between groups A and B. CONCLUSION: A 320-row dynamic contrast CT scanner can detect meningiomas with a high probability of severe adhesion toward the brain surface and postoperative intraparenchymal hematoma.
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Tomografía Computarizada Cuatridimensional/métodos , Neoplasias Meníngeas/cirugía , Meningioma/cirugía , Procedimientos Neuroquirúrgicos/efectos adversos , Hemorragia Posoperatoria/epidemiología , Adherencias Tisulares/epidemiología , Adulto , Anciano , Duramadre/irrigación sanguínea , Duramadre/diagnóstico por imagen , Femenino , Humanos , Masculino , Neoplasias Meníngeas/diagnóstico por imagen , Meningioma/diagnóstico por imagen , Persona de Mediana Edad , Neovascularización Patológica/diagnóstico por imagen , Neovascularización Patológica/cirugía , Procedimientos Neuroquirúrgicos/métodos , Hemorragia Posoperatoria/diagnóstico por imagen , Adherencias Tisulares/diagnóstico por imagen , Adherencias Tisulares/etiologíaRESUMEN
Approximately 20% of patients have persistent unexplained pain after total knee arthroplasty (TKA). Currently available treatments are unsatisfactory. The present report describes four patients in whom transcatheter arterial embolization had a remarkable effect on pain after TKA. Abnormal neovessels were identified in all patients. For 48 h, one patient experienced remarkable postprocedural pain at the inner side of the knee that was subsided by level 1 analgesics and another patient development of a spontaneous skin ulceration resolving within 8 days. The mean Knee injury and Osteoarthritis Outcome Score pain subtotal had increased from 39 to 82 one month after treatment. Endovascular occlusion of neovascularization, decreasing chronic inflammation and the growth of unmyelinated sensory nerves may be treatment options for persistent unexplained pain following TKA.Level of Evidence IV, Case report.
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Artroplastia de Reemplazo de Rodilla , Dolor Crónico/etiología , Procedimientos Endovasculares/métodos , Articulación de la Rodilla/irrigación sanguínea , Neovascularización Patológica/complicaciones , Neovascularización Patológica/cirugía , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Articulación de la Rodilla/cirugía , Masculino , Persona de Mediana Edad , Resultado del TratamientoAsunto(s)
Inhibidores de la Angiogénesis/uso terapéutico , Angiografía con Fluoresceína , Iris/irrigación sanguínea , Coagulación con Láser , Neovascularización Patológica/diagnóstico , Ranibizumab/uso terapéutico , Tomografía de Coherencia Óptica , Segmento Anterior del Ojo , Terapia Combinada , Humanos , Inyecciones Intravítreas , Masculino , Persona de Mediana Edad , Neovascularización Patológica/tratamiento farmacológico , Neovascularización Patológica/cirugía , Neovascularización Patológica/terapia , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidoresRESUMEN
Background Tetralogy of Fallot with major aortopulmonary collateral arteries is a heterogeneous form of pulmonary artery (PA) stenosis that requires multiple forms of intervention. We present a patient-specific in vitro platform capable of sustained flow that can be used to train proceduralists and surgical teams in current interventions, as well as in developing novel therapeutic approaches to treat various vascular anomalies. Our objective is to develop an in vitro model of PA stenosis based on patient data that can be used as an in vitro phantom to model cardiovascular disease and explore potential interventions. Methods and Results From patient-specific scans obtained via computer tomography or 3-dimensional (3D) rotational angiography, we generated digital 3D models of the arteries. Subsequently, in vitro models of tetralogy of Fallot with major aortopulmonary collateral arteries were first 3D printed using biocompatible resins and next bioprinted using gelatin methacrylate hydrogel to simulate neonatal vasculature or second-order branches of an older patient with tetralogy of Fallot with major aortopulmonary collateral arteries. Printed models were used to study creation of extraluminal connection between an atretic PA and a major aortopulmonary collateral artery using a catheter-based interventional method. Following the recanalization, engineered PA constructs were perfused and flow was visualized using contrast agents and x-ray angiography. Further, computational fluid dynamics modeling was used to analyze flow in the recanalized model. Conclusions New 3D-printed and computational fluid dynamics models for vascular atresia were successfully created. We demonstrated the unique capability of a printed model to develop a novel technique for establishing blood flow in atretic vessels using clinical imaging, together with 3D bioprinting-based tissue engineering techniques. Additive biomanufacturing technologies can enable fabrication of functional vascular phantoms to model PA stenosis conditions that can help develop novel clinical applications.
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Aorta Torácica/anomalías , Bioimpresión , Modelos Anatómicos , Neovascularización Patológica/patología , Impresión Tridimensional , Arteria Pulmonar/anomalías , Tetralogía de Fallot/complicaciones , Aorta Torácica/cirugía , Humanos , Neovascularización Patológica/cirugía , Planificación de Atención al Paciente , Arteria Pulmonar/cirugíaRESUMEN
PURPOSE: To evaluate the effects of clinical features associated with enucleation in eyes with Coats disease. METHODS: The medical records of all patients with Coats disease at the Ocular Oncology, Wills Eye Hospital from November 1, 1973, to July 31, 2018, were reviewed retrospectively. The clinical features pertaining to need for ultimate enucleation and time to enucleation were compared. RESULTS: The records of 351 eyes were reviewed, of which 259 had follow-up at our center and 32 (12%) were managed with enucleation. Reasons for enucleation included neovascular glaucoma (n = 24 [75%]), possible tumor (6 [19%]), and phthisis bulbi (2 [6%]). Compared to nonenucleated eyes, enucleated eyes had more extensive clock hour involvement of telangiectasia (P < 0.001), light bulb aneurysms (P < 0.001), exudation (P < 0.001), and subretinal fluid (P < 0.001). On adjusted analysis by binomial logistic regression, variables predictive of enucleation included presence of iris neovascularization (P = 0.01), ultrasonographic retinal detachment (P = 0.004), open-funnel retinal detachment (P = 0.04), closed-funnel retinal detachment (P = 0.01), ultrasonographic elevation of subretinal fluid by millimeters (P = 0.001), and angiographic extent of light bulb aneurysms by clock hours (P = 0.02). By Kaplan-Meier analysis of 4-year cumulative risk of enucleation, risk factors for enucleation included presence of iris neovascularization (hazard ratio [HR] 31.0; P < 0.001), ultrasonographic retinal detachment (HR 56.2; P < 0.001), open-funnel retinal detachment (HR 2.7; P = 0.01), and closed-funnel retinal detachment (HR 4.5; P < 0.001). CONCLUSIONS: Clinical features that predict risk of and time to enucleation in eyes with Coats disease include iris neovascularization, ultrasonographic presence and millimeter-elevation of retinal detachment, and angiographic extent of light bulb aneurysms.
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Aneurisma/diagnóstico , Enucleación del Ojo , Iris/irrigación sanguínea , Neovascularización Patológica/diagnóstico , Desprendimiento de Retina/diagnóstico , Telangiectasia Retiniana/diagnóstico , Vasos Retinianos/patología , Adolescente , Adulto , Anciano , Aneurisma/cirugía , Niño , Preescolar , Femenino , Angiografía con Fluoresceína , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Neovascularización Patológica/cirugía , Desprendimiento de Retina/cirugía , Telangiectasia Retiniana/cirugía , Estudios Retrospectivos , Líquido Subretiniano , Factores de Tiempo , UltrasonografíaRESUMEN
BACKGROUND: Numerous studies have shown that hepatocellular carcinoma (HCC) without microvascular invasion (MVI) may have better outcomes. This study established a preoperative MVI risk nomogram mainly incorporating three related risk factors of MVI in BCLC 0/A HCC after surgery. METHODS: Independent predictors for the risk of MVI were investigated, and an MVI risk nomogram was established based on 60 patients in the training group who underwent curative hepatectomy for BCLC 0/A HCC and validated using a dataset in the validation group. RESULTS: Univariate analysis in the training group showed that hepatitis viral B (HBV) DNA (P=0.034), tumor size (P<0.001), CT value in the venous phase (P=0.039), CT value in the delayed phase (P=0.017), peritumoral enhancement (P=0.013), visible small blood vessels in the arterial phase (P=0.002), and distance from the tumor to the inferior vena cava (IVC) (DTI, P=0.004) were risk factors significantly associated with the presence of MVI. According to multivariate analysis, the independent predictive factors of MVI, including tumor size (P=0.002), CT value in the delayed phase (P=0.018), and peritumoral enhancement (P=0.057), were incorporated in the corresponding nomogram. The nomogram displayed an unadjusted C-index of 0.851 and a bootstrap-corrected C-index of 0.832. Calibration curves also showed good agreement on the presence of MVI. ROC curve analyses showed that the nomogram had a large AUC (0.851). CONCLUSIONS: The proposed nomogram consisting of tumor size, CT value in the delayed phase, and peritumoral enhancement was associated with MVI risk in BCLC 0/A HCC following curative hepatectomy.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Microvasos , Neovascularización Patológica , Nomogramas , Adulto , Anciano , Carcinoma Hepatocelular/irrigación sanguínea , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/cirugía , Femenino , Humanos , Neoplasias Hepáticas/irrigación sanguínea , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/cirugía , Masculino , Microvasos/patología , Microvasos/cirugía , Persona de Mediana Edad , Invasividad Neoplásica , Neovascularización Patológica/patología , Neovascularización Patológica/cirugía , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Factores de RiesgoRESUMEN
Blood vessels are the important components of the circulatory systems that transport blood throughout the human body and maintain the homeostasis of physiological tissues. Pathologically, blood vessels are often affected by diseases, leading to the formation of unstable, irregular, and hyperpermeable blood vessels. In the tumor microenvironment, abnormal leakage of tumor blood vessels is related to the histological grade and malignant potential of tumors and may also facilitate metastasis of cancer. Visual diagnosis of blood vessels is very important for us to understand the occurrence and development of diseases. Multiphoton microscopy (MPM) is a potential label-free diagnostic tool based on second harmonic generation (SHG) and two-photon excited fluorescence (TPEF). MPM can effectively observe the morphological changes of biological tissues at the molecular and cellular levels. In this work, we demonstrate that label-free MPM can be used to visualize the microstructure of blood vessels in human normal breast and breast tumor tissue. Moreover, MPM can monitor the changes of blood vessels in tumor microenvironment. These results show that the MPM will become a promising technique for clinicians to study the properties of the microstructure of the blood vessels.
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Vasos Sanguíneos/diagnóstico por imagen , Neoplasias de la Mama/diagnóstico por imagen , Glándulas Mamarias Humanas/diagnóstico por imagen , Microscopía de Fluorescencia por Excitación Multifotónica/métodos , Neovascularización Patológica/diagnóstico por imagen , Vasos Sanguíneos/patología , Neoplasias de la Mama/irrigación sanguínea , Neoplasias de la Mama/patología , Neoplasias de la Mama/cirugía , Eosina Amarillenta-(YS) , Femenino , Hematoxilina , Humanos , Glándulas Mamarias Humanas/irrigación sanguínea , Glándulas Mamarias Humanas/patología , Glándulas Mamarias Humanas/cirugía , Mastectomía , Microscopía de Fluorescencia por Excitación Multifotónica/instrumentación , Neovascularización Patológica/patología , Neovascularización Patológica/cirugía , Adhesión en Parafina , Fijación del Tejido , Microambiente TumoralRESUMEN
OBJECTIVE: We aimed to assess the preoperative rectal cancer angiogenesis with Endorectal Power Doppler Ultrasonography by using the Power Doppler Vascularity Index (PDVI) calculated by imaging analysis software, and to compare it with the microvessel density (MVD) in surgical specimens PATIENTS AND METHODS: This study included 110 patients (39 females; mean age 61.5 years) with rectal cancer. Immunohistochemical staining of surgical specimens with anti-CD-31 antibody was used for MVD evaluation. The PDVI of each tumor was calculated using Endorectal Power Doppler with computer-assisted quantification of colour pixels. RESULTS: Mean MVD - 163 ± 69 microvessels/mm2 (50-328) was used as a cutoff point, differentiating two groups of tumors with high (> 160 mm2) and low (≤ 160 mm2) angiogenic activity. Mean PDVI of 8.9 ± 6.0% (0-27.3) was used as a cutoff point, dividing two groups of tumors with high (> 8%) and low (≤ 8%) PDVI. The MVD and the PDVI showed a good positive correlation (r = 0.438, p = 0.002). Patients with low PDVI had 25 months longer overall survival (p < 0.05) than patients with high PDVI. Patients with low MVD had 36 months longer survival (p < 0.05). CONCLUSIONS: Endorectal Power Doppler Ultrasonography is a reliable and noninvasive method for assessment of the extent of rectal cancer angiogenesis. Tumor angiogenesis assessed by the PDVI correlated with histological MVD determination and could predict survival rates. Endorectal Power Doppler examination is a useful and reproducible method for in vivo preoperative quantitative assessment of tumor vascularization.
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Neovascularización Patológica/patología , Neoplasias del Recto/patología , Ultrasonografía Doppler , Endosonografía , Femenino , Humanos , Persona de Mediana Edad , Neovascularización Patológica/cirugía , Estudios Prospectivos , Neoplasias del Recto/cirugía , Programas InformáticosRESUMEN
PURPOSE: To investigate the potential of colchicine to improve bleb function after trabeculectomy. METHODS: To find the maximum usable colchicine concentration, an ocular irritation study was performed with the Draize test at concentrations of 0.001%, 0.01% and 0.1%. Additionally, the synergistic effect of topical colchicine instillation and MMC application to surgical site was evaluated in a rabbit model by measuring changes after trabeculectomy in intraocular pressure (IOP) and bleb morphology score at 3, 7, 14, 21, 28, 35, 42, and 49 days. RESULTS: Experiments with a rabbit model of trabeculectomy showed that 0.04% MMC plus 0.01% colchicine was more effective than saline and 0.04% MMC alone in maintaining IOP reduction at days 7-49 (P < 0.01 at all time points) and day 49 (P < 0.05), respectively, while 0.04% MMC alone was more effective than saline only at days 7-35 (P < 0.05 at all time points). 0.04% MMC plus 0.01% colchicine and 0.04% MMC alone were more effective than saline at preserving bleb score at days 7-21 and 35-49 (P < 0.05 at all time points) and at days 7-35 (P < 0.05 at all time points), respectively. CONCLUSION: Colchicine may be a promising adjuvant for strengthening the effect of MMC and improving the survival of the filtering bleb in trabeculectomy.
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Vesícula/tratamiento farmacológico , Colchicina/uso terapéutico , Oftalmopatías/tratamiento farmacológico , Mitomicina/uso terapéutico , Neovascularización Patológica/tratamiento farmacológico , Trabeculectomía/métodos , Alquilantes/uso terapéutico , Animales , Vesícula/fisiopatología , Vesícula/cirugía , Quimioterapia Combinada , Oftalmopatías/cirugía , Masculino , Neovascularización Patológica/cirugía , Conejos , Moduladores de Tubulina/uso terapéuticoRESUMEN
BACKGROUND AND PURPOSE: Neovascularization (NV) is regarded to be one of the important features of vulnerable plaque. The purpose of this study was to evaluate associations between the presence of NV, detected using optical frequency domain imaging (OFDI), and ischemic events and the progress of carotid artery stenosis. MATERIALS AND METHODS: Carotid artery plaques were evaluated using an OFDI system before angioplasty. NV was defined as no-signal tubuloluminal structures recognized on at least 3 consecutive images. The total number of NVs was compared between symptomatic and asymptomatic plaques and between progressive and nonprogressive plaques. Carotid plaque was diagnosed as "progressive" when peak systolic velocity increased between serial carotid duplex scans. RESULTS: A total of 36 patients (17 symptomatic, 16 progressive) were included. The percentage of patients with smoking habits was significantly higher with progressive carotid plaque than with nonprogressive carotid plaque (P = 0.003). NV was detected in 34 patients (94%), and the total number of NVs was significantly higher with progressive carotid plaque (10.2 ± 4.8 vs. 3.7 ± 2.8; P < 0.0001). There was no relationship between the number of NVs and ischemic events (symptomatic 6.0 ± 5.1 vs. asymptomatic 7.1 ± 5.0; P = 0.47). In multivariate logistic regression analysis, the number of NVs was an independent predictor of progressive carotid plaque (odds ratio 1.64 per 1 increase [95% confidence interval 1.19-2.64]; P = 0.0005). CONCLUSIONS: NV was more frequently observed in progressive carotid plaques. Evaluation of NV using OFDI may be useful in predicting progressive carotid plaques.
Asunto(s)
Arterias Carótidas/cirugía , Estenosis Carotídea/cirugía , Neovascularización Patológica/cirugía , Placa Aterosclerótica/diagnóstico por imagen , Placa Aterosclerótica/cirugía , Anciano , Anciano de 80 o más Años , Estenosis Carotídea/diagnóstico por imagen , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neovascularización Patológica/diagnóstico por imagen , Imagen Óptica/métodos , Resultado del TratamientoRESUMEN
BACKGROUND: Neuropilins (NRPs) participate in many processes related to cancer development such as angiogenesis, lymphangiogenesis and metastasis. Although endometrial cancer is one of the most common gynecological cancers, it has not been studied in terms of NRPs expression. OBJECTIVE: The aim of this study was to investigate the potential utility of NRPs as important factors in the diagnosis and treatment of endometrial cancer. METHODS: Our study consisted of 45 women diagnosed with endometrial cancer at the following degrees of histological differentiation: G1, 17; G2, 15; G3, 13 cases. The control group included 15 women without neoplastic changes. The immunohistochemical reactions were evaluated using light microscopy. RESULTS: We did not detect the expression of NRP-1 and NRP-2 in the control group. NRP-1 expression was found exclusively in cancer cells. It was higher in G2 and G3 and reached about 190% of G1. NRP-2 expression was observed in the endothelium and was similar across all three cancer grades. In cancer cells, NRP-2 expression increased with the degree of histological differentiation. CONCLUSION: NRP1 and NRP2 are candidates for complementary diagnostic molecular markers and promising new targets for molecular, personalized anticancer therapies.
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Biomarcadores de Tumor/biosíntesis , Neoplasias Endometriales/metabolismo , Regulación Neoplásica de la Expresión Génica , Neuropilina-1/biosíntesis , Neuropilina-2/biosíntesis , Biomarcadores de Tumor/genética , Neoplasias Endometriales/patología , Neoplasias Endometriales/cirugía , Femenino , Humanos , Histerectomía , Neovascularización Patológica/metabolismo , Neovascularización Patológica/patología , Neovascularización Patológica/cirugía , Neuropilina-1/genética , Neuropilina-2/genética , Células Tumorales CultivadasRESUMEN
Perihilar cholangiocarcinoma (PHCCA) is the most common type of cholangiocarcinoma with low resection rate and high morbidity. The study of PHCCA biomarkers made progresses slowly compared with intrahepatic cholangiocarcinoma because of surgical complexity and low possibility of radical surgery, which resulted in the difficulty of specimen obtainment. To screen and identify new biomarkers in PHCCA, we constructed a retrospective cohort with 121 PHCCA patients and a prospective cohort consisting of 64 PHCCA patients, and screened the candidate biomarkers by immunohistochemistry and quantified PCR. In our study, expression of high mobility group box 1 (HMGB1) was demonstrated to be significantly associated with microvascular density (MVD) and unfavorable prognosis of PHCCA in both retrospective and prospective study. Moreover, HMGB1 concentrations in bile and serum of PHCCA patients and healthy controls were detected and compared. Postoperative serum HMGB1 and reflux cholangitis indicated recurrence and unfavorable prognosis of PHCCA. With experiments in vitro and in vivo, we demonstrated that intracellular HMGB1 could be released from PHCCA cells and induce invasion and angiogenesis with LPS stimulation. VEGFR2 expression in vessel endothelial cells was upregulated by the released HMGB1 from PHCCA, resulting in the ectopic angiogenesis. In conclusion, intracellular HMGB1 could be released from PHCCA cells and promote angiogenesis via elevating VEGFR2 in vessel endothelial cells. High expression of HMGB1 was associated with MVD and poor prognosis in clinical analyzation. Postoperative serum HMGB1 and cholangitis could predict high recurrence and unfavorable prognosis.
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Neoplasias de los Conductos Biliares , Proteína HMGB1/sangre , Tumor de Klatskin , Proteínas de Neoplasias/sangre , Neovascularización Patológica , Neoplasias de los Conductos Biliares/sangre , Neoplasias de los Conductos Biliares/mortalidad , Neoplasias de los Conductos Biliares/cirugía , Supervivencia sin Enfermedad , Células Endoteliales/metabolismo , Células Endoteliales/patología , Femenino , Humanos , Tumor de Klatskin/sangre , Tumor de Klatskin/mortalidad , Tumor de Klatskin/cirugía , Masculino , Neovascularización Patológica/sangre , Neovascularización Patológica/mortalidad , Neovascularización Patológica/cirugía , Estudios Prospectivos , Tasa de SupervivenciaRESUMEN
A 41-year-old woman (gravida 2, para 1) underwent elective termination of pregnancy at approximately 7 weeks of gestation. At 1 month after the elective abortion, she was referred due to abnormal results in a cervical cytological examination. Transvaginal ultrasonography showed a heterogeneous mass of 16 mm in diameter in the left adnexal region. At 3 months after her referral, the asymptomatic left adnexal mass had increased to 55 mm in diameter. Prominent vascular flow was detected in the solid portion by color Doppler ultrasonography. Magnetic resonance imaging showed suspected hemorrhage in the left adnexal cystic mass. Three-dimensional computerized tomographic angiography showed the prominent development of tortuous blood vessels in the left adnexal region, which originated from the left ovarian artery. The patient had a negative ß-human chorionic gonadotropin (hCG) level. Left salpingectomy was performed by a single-port laparoscopic approach. A pathological examination revealed degenerated villous tissue with ß-hCG-positive syncytiotrophoblasts.
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Enfermedades de los Anexos/diagnóstico por imagen , Gonadotropina Coriónica Humana de Subunidad beta/sangre , Neovascularización Patológica/diagnóstico por imagen , Embarazo Tubario/diagnóstico por imagen , Enfermedades de los Anexos/sangre , Enfermedades de los Anexos/cirugía , Adulto , Femenino , Humanos , Neovascularización Patológica/sangre , Neovascularización Patológica/cirugía , Embarazo , Embarazo Tubario/sangre , Embarazo Tubario/cirugía , SalpingectomíaRESUMEN
Mounting evidence demonstrates that expression of ERO1α, an endoplasmic reticulum (ER)-resident oxidase, is a poor prognosis factor in a variety of human cancers. However, the clinical relevance of ERO1α and its molecular mechanisms underlying tumor progression have not been determined for hepatocellular carcinoma (HCC). ERO1α expression levels in HCC tissues and cells were detected by quantitative real-time PCR and western blotting. ERO1α shRNAs and overexpression vector were transfected into HCC cells to downregulate or upregulate ERO1α expression. In vitro and in vivo assays were performed to investigate the function of ERO1α in invasion, metastasis, and angiogenesis of HCC. We found high ERO1α expression in HCC tissues and cells that was significantly associated with metastasis and poor clinicopathologic features of vascular invasion, advanced Edmondson Grade, and TNM stage. Loss-of-function and gain-of-function studies showed that ERO1α prompted migration, invasion, epithelial-mesenchymal transition (EMT), and angiogenesis of HCC cells both in vitro and in vivo. Further studies verified a positive correlation between ERO1α and S1PR1, upregulated in metastatic HCC tissues compared with HCC tissues without metastasis. S1PR1 knockdown markedly diminished the effects of ERO1α on HCC cell migration, invasion and vascular endothelial growth factor (VEGF) expression. Most importantly, ERO1α knockdown significantly repressed the death of HCC xenograft mouse models by reducing tumor distant metastasis, and host angiogenesis by suppressing the expression of S1PR1, p-STAT3, and VEGF-A in HCC cells. Our findings suggest that ERO1α is significantly correlated with reduced survival and poor prognosis, and promotes HCC metastasis and angiogenesis by triggering the S1PR1/STAT3/VEGF-A signaling pathway. ERO1α might be a novel candidate in HCC prognosis and therapy.
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Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Neoplasias Pulmonares/genética , Glicoproteínas de Membrana/genética , Neovascularización Patológica/genética , Oxidorreductasas/genética , Factor de Transcripción STAT3/genética , Receptores de Esfingosina-1-Fosfato/genética , Factor A de Crecimiento Endotelial Vascular/genética , Anciano , Animales , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/secundario , Carcinoma Hepatocelular/cirugía , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Transición Epitelial-Mesenquimal/genética , Femenino , Regulación Neoplásica de la Expresión Génica , Xenoinjertos , Humanos , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/cirugía , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/secundario , Neoplasias Pulmonares/cirugía , Masculino , Glicoproteínas de Membrana/antagonistas & inhibidores , Glicoproteínas de Membrana/metabolismo , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Persona de Mediana Edad , Estadificación de Neoplasias , Neovascularización Patológica/mortalidad , Neovascularización Patológica/patología , Neovascularización Patológica/cirugía , Oxidorreductasas/antagonistas & inhibidores , Oxidorreductasas/metabolismo , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/metabolismo , Factor de Transcripción STAT3/metabolismo , Transducción de Señal , Receptores de Esfingosina-1-Fosfato/metabolismo , Análisis de Supervivencia , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have become the standard first-line treatment for advanced lung adenocarcinoma (LUAD) cancer patients with activating EGFR mutations. However, most patients show acquired resistance to EGFR-TKIs, thereby resulting in a modest overall survival benefit. Here, we found that expression level of APE1 was closely associated with TKI resistance in LUAD. Our clinical data show that level of APE1 was inversely correlated with progression-free survival rate and median time to progression in EGFR-mutated LUAD patients. Additionally, we observed increased expression of APE1 in TKI-resistant LUAD cell lines compared to their parental cell lines. Overexpression of APE1-protected TKI-sensitive LUAD cells from TKI-induced cell growth inhibition and cell death. In contrast, inhibition of APE1-enhanced TKI-induced apoptosis, cell growth inhibition and tumor growth inhibition in TKI-resistant LUAD. In addition, we identified that APE1 positively regulates Akt activation and APE1 overexpression-induced TKI resistance was attenuated by inhibition of Akt activity. Finally, we demonstrated that inhibition of the redox function of APE1 enhances the sensitivity of TKI-resistant LUAD cells to TKI treatment and inhibits Akt phosphorylation in TKI-resistant LUAD cells, but not by inhibition of the APE1 DNA repair function. Taken together, our data show that increased expression of APE1 significantly contributes to TKI resistance development in LUAD, and targeting APE1 may reverse acquired resistance of LUAD cells to TKI treatment. Additionally, our data show that APE1 regulates TKI resistance in LUAD cells by activating Akt signaling through a redox-dependent mechanism.