Los retos en la evaluación radiológica de las metástasis cerebrales, más allá de la progresión / Challenges in radiological evaluation of brain metastases, beyond progression

La resonancia magnética es la piedra angular en la evaluación de las metástasis cerebrales. Los retos clínicos residen en discriminar las metástasis de imitadores como infecciones o tumores primarios y en evaluar la respuesta al tratamiento. Este, en ocasiones, condiciona un crecimiento, que debe encuadrarse como una pseudoprogresión o una radionecrosis, ambos fenómenos inflamatorios atribuibles al mismo, o bien considerarse como una recurrencia. Para responder a estas necesidades, las técnicas de imagen son objeto de constantes investigaciones. No obstante, un crecimiento exponencial tras la radioterapia debe interpretarse con cautela, incluso ante resultados sospechosos de progresión por técnicas avanzadas, ya que puede tratarse de una radionecrosis. El objetivo de este trabajo es familiarizar al lector con los fenómenos inflamatorios de las metástasis cerebrales tratadas con radioterapia y describir dos signos radiológicos relacionados: la «nube inflamatoria» y el «realce en anillo incompleto», con el fin de adoptar un manejo conservador en estos casos.(AU)

MRI is the cornerstone in the evaluation of brain metastases. The clinical challenges lie in discriminating metastases from mimickers such as infections or primary tumors and in evaluating the response to treatment. The latter sometimes leads to growth, which must be framed as pseudo-progression or radionecrosis, both inflammatory phenomena attributable to treatment, or be considered as recurrence. To meet these needs, imaging techniques are the subject of constant research. However, an exponential growth after radiotherapy must be interpreted with caution, even in the presence of results suspicious of tumor progression by advanced techniques, because it may be due to inflammatory changes. The aim of this paper is to familiarize the reader with inflammatory phenomena of brain metastases treated with radiotherapy and to describe two related radiological signs: «the inflammatory cloud» and «incomplete ring enhancement», in order to adopt a conservative management with close follow-up.(AU)

Challenges in radiological evaluation of brain metastases, beyond progression.

MRI is the cornerstone in the evaluation of brain metastases. The clinical challenges lie in discriminating metastases from mimickers such as infections or primary tumors and in evaluating the response to treatment. The latter sometimes leads to growth, which must be framed as pseudo-progression or radionecrosis, both inflammatory phenomena attributable to treatment, or be considered as recurrence. To meet these needs, imaging techniques are the subject of constant research. However, an exponential growth after radiotherapy must be interpreted with caution, even in the presence of results suspicious of tumor progression by advanced techniques, because it may be due to inflammatory changes. The aim of this paper is to familiarize the reader with inflammatory phenomena of brain metastases treated with radiotherapy and to describe two related radiological signs: "the inflammatory cloud" and "incomplete ring enhancement", in order to adopt a conservative management with close follow-up.

Structural Analysis of Cu+ and Cu2+ Ions in Zeolite as a Nanoreactor with Antibacterial Applications.

In this work, we report the structural analysis of Cu+ and Cu2+ ions in zeolite as a nanoreactor with antibacterial applications. A simple one-step process was implemented to obtain Cu ions in zeolite A (ZA4) by controlling the temperature in the solutions to guarantee the ions' stability. Samples were characterized by scanning electron microscopy, energy-dispersive X-ray spectroscopy, and Fourier transform infrared (FT-IR) spectroscopy, showing the characteristic zeolite elements as well as the characteristic bands with slight modifications in the chemical environment of the zeolite nanoreactor attributed to Cu ions by FT-IR spectroscopy. In addition, a shift of the characteristic peaks of ZA4 in X-ray diffraction was observed as well as a decrease in relative peak intensity. On the other hand, the antibacterial activity of Cu ions in the zeolite nanoreactor was evaluated.

Bevacizumab dose adjustment to improve clinical outcomes of glioblastoma.

BACKGROUND: Glioblastoma (GBM) is one of the most aggressive and vascularized brain tumors in adults, with a median survival of 20.9 months. In newly diagnosed and recurrent GBM, bevacizumab demonstrated an increase in progression-free survival, but not in overall survival. METHODS: We conducted an in silico analysis of VEGF expression, in a cohort of 1082 glioma patients. Then, to determine whether appropriate bevacizumab dose adjustment could increase the anti-angiogenic response, we used in vitro and in vivo GBM models. Additionally, we analyzed VEGFA expression in tissue, serum, and plasma in a cohort of GBM patients before and during bevacizumab treatment. RESULTS: We identified that 20% of primary GBM did not express VEGFA suggesting that these patients would probably not respond to bevacizumab therapy as we proved in vitro and in vivo. We found that a specific dose of bevacizumab calculated based on VEGFA expression levels increases the response to treatment in cell culture and serum samples from mice bearing GBM tumors. Additionally, in a cohort of GBM patients, we observed a correlation of VEGFA levels in serum, but not in plasma, with bevacizumab treatment performance. CONCLUSIONS: Our data suggest that bevacizumab dose adjustment could improve clinical outcomes in Glioblastoma treatment.

Analysis of expression of PTEN/PI3K pathway and programmed cell death ligand 1 (PD-L1) in malignant pleural mesothelioma (MPM).

BACKGROUND: Malignant pleural mesothelioma (MPM) frequently express elevated AKT/mTOR activity. Previous reports in gliomas, colon, breast and prostate cancer suggest that PTEN/PI3K pathway may be important for the induction of PD-L1 expression. This study explored the expression of PTEN/PI3K pathway and PD-L1 in MPM and its relationship with the patient́s prognosis MATERIAL AND METHODS: Twenty seven consecutive MPM patients were reviewed. Formalin-fixed, paraffin-embedded tissue biopsies were used for immunohistochemical analysis of PTEN/PI3K pathway and PD-L1 RESULTS: Expression of PTEN, mTOR, pAKT, p4EBP1, peif4E, pS6 and FOXO3a was found in 88.5%, 92.3%, 78.3%, 38.5%, 100%, 52.2% and 100% of tumors and PD-L1 in 23%. We found a significant correlation between pAKT, FOXO3a and PD-L1 expression and longer overall survival (p <0.05). We did not identify significant association between the level of PD-L1 expression and alterations in PI3K pathway CONCLUSIONS: This study shows PTEN/PI3K pathway and PD-L1 in MPM are frequently activated. Our results suggests that there is not association between PD-L1 and the involvement of the PI3K pathway in MPM.

A very rare case of vaginal angiokeratoma.

Angiokeratomas are benign, vascular lesions that are very rarely identified in the vagina. A patient originally presented with endometrial cancer in 1993 and was cured following surgery and adjuvant radiotherapy. However, in 2007, she developed multiple, erythematous, vaginal nodules that were eventually diagnosed as angiokeratoma of the vagina. The diagnosis of vaginal angiokeratoma may not be initially suspected. Therefore, physicians should perform a histologic examination to verify the condition and accordingly, provide relevant clinical management.

Influencia de variables clínicas y lipídicas en la magnitud de la lipemia postradial de sujetos con y sin hipertrigliceridemia / Influence of clinical and lipid variables on the magnitude of postprandial lipemia in subjects with and without hipertriglyceridemia

Introducción. La lipemia postprandial se caracteriza por el aumento de la permanencia en circulación de lipoproteínas ricas en triglicéridos que pueden producir aterosclerosis siendo esta una importante causa de muerte en nuestro medio Objetivo. Evaluar el efecto de variables lipídicas y antropométricas en la magnitud de la lipemia postprandial de sujetos con y sin hipertrigliceridemia Material y métodos. Se estudiaron 48 sujetos de uno y otro género, con triglicéridos basales mayores a 200mg/dL, que ingirieron una carga lipídica estandarizada (desayuno con 30g de grasa) y fueron seguidos durante siete horas recolectando sangre total cada hora para determinar los triglicéridos postprandiales y con estos datos hallar la magnitud de la lipemia postprandial. Este dato se correlacionó con variables clínicas como la edad, el índice de masa corporal, la circunferencia de la cintura, entre otras y con variables lipídicas como colesterol total, colesterol de HDL y LDL y triglicéridos basales Resultados. Se encontró alteración en el aclaramiento de triglicéridos postprandiales en sujetos que tenían una concentración basal de triglicéridos por encima de 186 mg/dl. Las variables clínicas que más correlacionaron con la magnitud de la lipemia postprandial fueron la edad (p=0.009) y el perímetro de la cintura (p=0.043), mientras que las variables lipídicas mejor relacionadas con la lipemia postprandial fueron la concentración de triglicéridos basales (p=<0.001), el colesterol VLDL (p=<0.001) y el colesterol HDL (p=0.041) Conclusión. Las variables que podrían predecir el comportamiento de los triglicéridos postprandiales en los individuos de este estudio son la edad, el perímetro de la cintura, el colesterol VLDL, el colesterol HDL y la concentración de triglicéridos basales.

Influence of the diet made by its family ancestors in the hereditary component of an individual: study in six generations of rats.

BACKGROUND: The prevalence of the deficiency of enzyme Lactase/phlorizin hydrolase (LPH) varies widely between different countries, with a low of 1-3% in Scandinavia and close to 100% in most of South-East Asia. Various carbohydrates are capable of enhancing LPH mRNA levels in the small intestine, and that transcriptional control plays a major role in the carbohydrate-induced alterations of LPH mRNA expression. MATERIAL AND METHODS: A generation of rats was randomized and assigned to two groups; those that were fed a high-carbohydrate diet and, those that were fed standard rodent meal. The sixth generation of these animals was fed standard rodent meal. Transfection experiments using Caco-2 cells were performed using sperm samples of the sixth generation of rats. RESULTS: This study suggests that the feeding with a high-carbohydrate diet during five generations of rats increases the capacity of production of enzyme LPH, LPH mRNA levels and the transcription rate of the LPH gene in the sixth generation of these animals, and this fact happens independently of the diet that this generation of rats had. Transfection experiments show that this influence has had to take place necessarily within the hereditary component which the last generation of rats received from its family ancestors. CONCLUSION: The feeding received by the ancestors of a generation of rats could influence within hereditary component received by them.

Artificial antigen-presenting cells as a tool to exploit the immune 'synapse'.

Recent progress in molecular medicine has provided important tools to identify antigen-specific T cells. In most cases, the approach is based on oligomeric combinations of recombinant major histocompatibility complex-peptide complexes fixed to various rigid supports available for binding by the T-cell receptor. These tools have greatly increased our insight into mechanisms of immune responses mediated by CD8+ T cells. Examples of the diverse fields of application for this technology include immunization, viral infections and oral tolerance induction.

Color Doppler image of central retinal artery of eyes with an intraconal mass.

PURPOSE: Retinal ischemia secondary to hypoperfusion of the central retinal artery is recognized as one factor that may contribute to the development of loss of vision in eyes with intraorbital tumors. We study intraorbital tumors which produce motility disturbances and visual problems by color Doppler imaging to evaluate this factor. METHODS: We examined the central retinal artery velocities of 3 patients with disc edema caused by intraconal masses (2 cavernous hemangiomas and 1 presumed optic nerve glioma) via color Doppler imaging. RESULTS: The time-velocity waveform demonstrated abnormally high vascular resistance in the central retinal artery of all affected eyes in the primary position compared with the normal waveform seen in the other eyes. We compared the pulsatility index of eyes with an intraconal mass and contralateral, control eyes using Student's t test for paired samples and significant differences were noted between both groups (p< 0.01). CONCLUSIONS: Intraconal tumors could produce increased pressure in the optic nerve sheath and the optic nerve tissue which could be associated with impaired retinal and optic nerve blood flow and the subsequent amaurosis encountered with intraorbital tumors.

Endogenous endophthalmitis caused by Rickettsia conorii.

PURPOSE: We report herein the first confirmed case of endogenous endophthalmitis caused by Rickettsia conorii. METHODS: Indirect immunofluorescence was performed in peripheral blood with antibodies against Rickettsia conorii. A vitreous aspirate was studied by indirect immunofluorescence with antibodies against Rickettsia conorii and by direct immunofluorescence with conjugated antigen against Rickettsia conorii. RESULTS: Indirect immunofluorescence in peripheral blood gave a titre of 1/320 at that moment and 1/640 fifteen days later. The vitreous aspirate studied by indirect immunofluorescence gave a titre of 1/620 and it showed a positive reaction to Rickettsia conorii antigen by direct immunofluorescence. CONCLUSION: Rickettsia conorii should be considered in the differential diagnosis of endogenous endophthalmitis in areas where Mediterranean spotted fever is endemic.

[Color Doppler echography study of ocular blood flow velocity in patients with proliferative diabetic retinopathy after performance of retinal pan-photocoagulation: 2 years' follow-up]. / Estudio mediante ecografía Doppler color de las velocidades de flujo sanguíneo ocular en pacientes afectos de retinopatía diabética proliferante tras la realización de panfotocoagulación retiniana: dos años de seguimiento.

PURPOSE: Color Doppler imaging allows for simultaneous two-dimensional anatomical imaging and Doppler measurement of blood flow velocity. Because hemodynamic changes have been seen in diabetic patients after photocoagulation by other techniques, the authors compared 25 eyes with proliferative diabetic retinopathy before, 6 months, 1 year, and 2 years after panretinal photocoagulation with a matched control group of 30 healthy volunteers. METHODS: The ophthalmic artery, short posterior ciliary artery, central retinal vessels and vortex veins of all patients were examined, and the systolic, diastolic and mean arterial velocities were measured. Panretinal photocoagulation was performed with these parameters: 800-1000 spots, 0.1s, 500 micron argon laser. RESULTS: Student's t test revealed that the perfusion velocity was significantly lower in diabetic patients than in normals (Vsystolic in the ophthalmic artery: 31.7 (6.7) cm/s vs 36.6 (7.0) cm/s, respectively, P = 0.03). After treatment, blood flow velocities were significantly lower than before photocoagulation (Vsystolic in the ophthalmic artery: 6 months after treatment 26.9 (7.2) cm/s, P = 0.018 and 1 year after photocoagulation 25.5 (7.0) cm/s, P = 0.009; and 2 years after photocoagulation, 25.7 (6.8) cm/s, P = 0.01). No statistically significant differences were found between 6 months, 1 year, and 2 years after panretinal photocoagulation. No significant correlations were found between age and blood velocities in diabetics and healthy volunteers. CONCLUSIONS: Eyes with proliferative diabetic retinopathy showed lower ocular perfusion velocities than normals. Photocoagulation resulted in a reduction in ocular blood flow velocities; these values did not change during 2 years of follow-up.

Effect of nylon suture diameter on induced astigmatism after phacoemulsification.

PURPOSE: To prospectively compare the clinical results of 10-0 and 9-0 monofilament nylon sutures after phacoemulsification with poly(methyl methacrylate) intraocular lens implantation through a 4.0 mm cruciate incision. SETTING: Department of Ophthalmology, Ramón y Cajal Hospital, Madrid, Spain. METHODS: One hundred eyes with cataract were randomly assigned to have surgery using a 10-0 or a 9-0 nylon suture. Except for suture diameter, identical surgical methods were used in every case. Data on uncorrected visual acuity, keratometry and postoperative astigmatism were analyzed up to 12 months after surgery. RESULTS: Both groups had similar uncorrected visual acuity. Mean postoperative corneal astigmatism was against the rule in the 10-0 nylon suture group and with the rule in the 9-0 nylon suture group. Significant differences were found between groups (P < .05). CONCLUSION: Both suture diameters offered satisfactory clinical results. Patients with preoperative with-the-rule astigmatism might benefit from 10-0 nylon sutures and those with preoperative against-the-rule astigmatism, from 9-0 nylon sutures.

Influence of a dilated pupil on the visual field in glaucoma.

PURPOSE: The author studied the effects of pupillary dilation on perimetry in a group of glaucomatous patients receiving timolol therapy. PATIENTS AND METHODS: A prospective study compared the visual fields of 23 patients with primary open-angle glaucoma of varying severity (mean defect: 3.84; short-term fluctuation: 1.91; pattern standard deviation [SD]: 3.61; corrected pattern SD: 3.12) before and after instillation of phenylephrine 10% using the Octopus 1-2-3 projection perimeter (INTERZEAG AG, Schlieren, Switzerland). RESULTS: The mean defect became impaired by an average of 3.01 (SD +/- 1.52) dB after administration of phenylephrine (p < 0.001). The pattern SD and the corrected pattern SD also became impaired with dilation by 1.51 dB (p < 0.01) and 1.73 dB (p < 0.05), respectively, after dilation. These changes varied across the visual field. The outer zone of the visual field had the greatest impairment after dilation with phenylephrine. CONCLUSIONS: Pupillary dilation in patients with glaucoma produces a nonuniform decrease in threshold sensitivities that is statistically greater on outer zone of the visual field.

Frequency of induced astigmatism following phacoemulsification with suturing versus without suturing.

BACKGROUND AND OBJECTIVES: To compare the postoperative astigmatism between sutured wounds and nonsutured wounds after cataract surgery with a 3.2-mm scleral tunnel incision. PATIENTS AND METHODS: One hundred ten eyes of 110 patients were studied. Eyes with cataracts were randomly assigned to either the sutured or the unsutured procedure. Identical surgical methods were used in every case except for wound closure technique. Data on uncorrected visual acuity and induced astigmatism were analyzed for 6 months after the surgery. RESULTS: Both groups displayed similar uncorrected visual acuity. Mean induced corneal astigmatism was "against-the-rule" with both techniques, and it remained stable during the study. No significant differences were found between the two groups (P > .1). CONCLUSION: This study has shown that the differences in surgically induced astigmatisms of sutured wounds and nonsutured wounds after cataract surgery were not statistically significant when a 3.2-mm self-sealing incision was used.

Ocular blood flow velocities in patients with proliferative diabetic retinopathy after panretinal photocoagulation.

Color Doppler imaging allows for simultaneous two-dimensional anatomical imaging and Doppler measurement of blood-flow velocity. Because hemodynamic changes have been seen in diabetic patients after photocoagulation by other techniques, the author compared 25 eyes of 25 patients with proliferative diabetic retinopathy before and 6 months and 1 year after panretinal photocoagulation with a matched control group of 30 eyes of 30 healthy volunteers. The ophthalmic artery, short posterior ciliary artery, central retinal vessels, and vortex veins of all patients were examined, and the systolic, diastolic, and mean arterial velocities were measured. Panretinal photocoagulation was performed with these parameters: 800-1000 spots, 0.1 second, 500 microm argon laser. The blood velocity was significantly lower in diabetic patients than in normals in the ophthalmic artery and the central retinal artery. After treatment, blood-flow velocities were significantly lower than before photocoagulation in the ophthalmic artery, the central retinal artery and the central retinal vein. No statistically significant differences were found between 6 months and 1 year after panretinal photocoagulation. No significant correlations were found between age and blood velocities in diabetics and healthy volunteers. Eyes with proliferative diabetic retinopathy showed lower ocular perfusion velocities than normals in the ophthalmic artery and the central retinal artery. Photocoagulation resulted in a reduction in ocular blood-flow velocities in the ophthalmic artery, the central retinal artery and the central retinal vein; these values did not change significantly during 1 year of follow-up.

Intraocular lens implantation through 3.2 versus 4.0 mm incisions.

PURPOSE: To prospectively compare the clinical results of two small incision cataract surgery procedures: silicone intraocular lens (IOL) implantation through a 3.2 mm incision and poly(methyl methacrylate) IOL implantation through a 4.0 mm cruciate incision. SETTING: Department of Ophthalmology, Ramón y Cajal Hospital, Madrid, Spain. METHODS: One hundred twenty eyes with cataract were randomly assigned to either procedure. Except for incision width, identical surgical methods were used in every case. Data on uncorrected visual acuity, keratometry, and postoperative astigmatism were analyzed up to 6 months after surgery. RESULTS: Both groups had similar uncorrected visual acuities. Mean postoperative corneal astigmatism was against the rule with both techniques, and it remained stable during the study. No significant differences between groups were found (P > .1). CONCLUSION: Both procedures offered satisfactory clinical results and were associated with postoperative against-the-rule astigmatism despite the use of the nylon suture.

Comparative study of astigmatism through superior and lateral small incisions.

PURPOSE: To prospectively compare the clinical results of two cataract surgery procedures through a 4.0-mm incision, differing only in the wound location (superior or lateral). METHODS: 168 eyes with cataract were randomly assigned to either procedure. Except for incision location, surgical methods were identical. Uncorrected visual acuity, keratometry and postoperative astigmatism were analyzed up to six months for after surgery. RESULTS: Both groups had similar uncorrected visual acuity. Eyes in the superior incision group had significantly larger "against-the-rule" changes than those in the lateral incision group, and differences were significant at all measurement points from one week through six months after surgery. Patients with preoperative "with-the rule" astigmatism had smaller postoperative astigmatism after a superior incision and those with preoperative "against-the rule" astigmatism had less postoperative cylinder after a lateral incision. Differences between these groups were significant. CONCLUSIONS: Both procedures gave satisfactory clinical results. Postoperative astigmatism could depend on the preoperative astigmatism and the wound location.