Post-transplant lymphoproliferative disorders in a cohort of adult patients with a liver transplant from a reference hospital in Bogotá, Colombia / Trastornos linfoproliferativos en una cohorte de pacientes adultos con trasplante hepático atendidos en un hospital de referencia en Bogotá, Colombia.

Introduction: The post-transplant lymphoproliferative disorders (PTLD) are characterized by an uncontrolled pathological lymphoid proliferation as a consequence of transplant immunosuppression therapy. Objective: To characterize the clinical and pathological characteristics of PTLD in a cohort of adult patients with liver transplant during a 15 year period at the Hospital Universitario Fundación Santa Fe de Bogota. Materials and methods: We conducted an observational retrospective study by searching for the PTLD cases diagnosed during the study period in the databases of the Liver Transplantation Unit and the Pathology Department. We collected the epidemiological, clinical, and pathological information and performed the corresponding statistics analyses. Results: During the research period, 572 patients were transplanted; the incidence of PTDL was 2.44%; 79% of them were man and the average age at the time of diagnosis was 62.5 years; 71% of the cases were diagnosed during the first year after the transplant and the same percentage EBV-seropositive patients. The most frequent pathological phenotype was monomorphic and the majority of tumors was detected in the hepatic hilum. The one-year survival was 50%. Conclusion: The high proportion of early cases and the high frequency of Epstein-Barr virus seropositivity both in donors and receptors drewour attention. More studies are necessary to have a better understanding of this condition in Colombia. This is the first PTLD clinical and pathological analysis in liver-transplant patients from Colombia to date.

Introducción. Los trastornos linfoproliferativos después de un trasplante se caracterizan por la proliferación descontrolada de linfocitos como consecuencia del tratamiento inmunosupresor posterior a este. Objetivo. Caracterizar clínica y patológicamente los casos de trastornos linfoproliferativos después de trasplante (Post-Transplant Lymphoproliferative Disorders, PTLD) en una cohorte de pacientes adultos con trasplante de hígado atendidos a lo largo de 15 años en el Hospital Universitario Fundación Santa Fe de Bogotá. Materiales y métodos. Se hizo un estudio observacional retrospectivo a partir de la revisión de las bases de datos de la Unidad de Trasplante Hepático y del Departamento de Patología del Hospital en busca de los casos de PTLD diagnosticados durante el periodo de estudio. Se recolectó la información epidemiológica, clínica y patológica, y se adelantaron los análisis estadísticos. Resultados. Durante el periodo de estudio, hubo 572 pacientes con trasplante de hígado, la incidencia de trastornos linfoproliferativos fue de 2,44 %, el 79 % en hombres, y la edad promedio en el momento del diagnóstico fue de 62,5 años. El 71 % de los casos se presentó durante los primeros 12 meses después del trasplante y el mismo porcentaje fue seropositivo para el virus de Epstein-Barr (EBV). El fenotipo patológico más frecuente fue el monomorfo y la mayoría de los tumores se detectaron en el hilio hepático. La supervivencia al año fue del 50 %. Conclusiones. Llamó la atención el alto porcentaje de casos de presentación temprana, así como la gran frecuencia de seropositividad para el EBV tanto en los donantes como en los receptores. Deben adelantarse estudios más detallados para una mejor comprensión de esta enfermedad en el país. Este es el primer análisis clínico y patológico de PTLD en pacientes con trasplante de hígado adelantado en Colombia hasta la fecha.

Trastornos linfoproliferativos en una cohorte de pacientes adultos con trasplante hepático atendidos en un hospital de referencia en Bogotá, Colombia / Post-transplant lymphoproliferative disorders in a cohort of adult patients with a liver transplant from a reference hospital in Bogotá, Colombia

Introducción. Los trastornos linfoproliferativos después de un trasplante se caracterizan por la proliferación descontrolada de linfocitos como consecuencia del tratamiento inmunosupresor posterior a este. Objetivo. Caracterizar clínica y patológicamente los casos de trastornos linfoproliferativos después de trasplante (Post-Transplant Lymphoproliferative Disorders, PTLD) en una cohorte de pacientes adultos con trasplante de hígado atendidos a lo largo de 15 años en el Hospital Universitario Fundación Santa Fe de Bogotá. Materiales y métodos. Se hizo un estudio observacional retrospectivo a partir de la revisión de las bases de datos de la Unidad de Trasplante Hepático y del Departamento de Patología del Hospital en busca de los casos de PTLD diagnosticados durante el periodo de estudio. Se recolectó la información epidemiológica, clínica y patológica, y se adelantaron los análisis estadísticos. Resultados. Durante el periodo de estudio, hubo 572 pacientes con trasplante de hígado, la incidencia de trastornos linfoproliferativos fue de 2,44 %, el 79 % en hombres, y la edad promedio en el momento del diagnóstico fue de 62,5 años. El 71 % de los casos se presentó durante los primeros 12 meses después del trasplante y el mismo porcentaje fue seropositivo para el virus de Epstein-Barr (EBV). El fenotipo patológico más frecuente fue el monomorfo y la mayoría de los tumores se detectaron en el hilio hepático. La supervivencia al año fue del 50 %. Conclusiones. Llamó la atención el alto porcentaje de casos de presentación temprana, así como la gran frecuencia de seropositividad para el EBV tanto en los donantes como en los receptores. Deben adelantarse estudios más detallados para una mejor comprensión de esta enfermedad en el país. Este es el primer análisis clínico y patológico de PTLD en pacientes con trasplante de hígado adelantado en Colombia hasta la fecha.

Introduction: The post-transplant lymphoproliferative disorders (PTLD) are characterized by an uncontrolled pathological lymphoid proliferation as a consequence of transplant immunosuppression therapy. Objective: To characterize the clinical and pathological characteristics of PTLD in a cohort of adult patients with liver transplant during a 15 year period at the Hospital Universitario Fundación Santa Fe de Bogota. Materials and methods: We conducted an observational retrospective study by searching for the PTLD cases diagnosed during the study period in the databases of the Liver Transplantation Unit and the Pathology Department. We collected the epidemiological, clinical, and pathological information and performed the corresponding statistics analyses. Results: During the research period, 572 patients were transplanted; the incidence of PTDL was 2.44%; 79% of them were man and the average age at the time of diagnosis was 62.5 years; 71% of the cases were diagnosed during the first year after the transplant and the same percentage EBV-seropositive patients. The most frequent pathological phenotype was monomorphic and the majority of tumors was detected in the hepatic hilum. The one-year survival was 50%. Conclusion: The high proportion of early cases and the high frequency of Epstein-Barr virus seropositivity both in donors and receptors drewour attention. More studies are necessary to have a better understanding of this condition in Colombia. This is the first PTLD clinical and pathological analysis in liver-transplant patients from Colombia to date.

Multicenter, Randomized Clinical Trial to Assess the Effectiveness of Intravitreal Injections of Bevacizumab, Triamcinolone, or Their Combination in the Treatment of Diabetic Macular Edema.

BACKGROUND AND OBJECTIVE: To evaluate the efficacy of combined bevacizumab-triamcinolone intravitreal injection in the treatment of diabetic macular edema (DME) compared to monotherapy. PATIENTS AND METHODS: At eight clinical sites, 111 patients with DME were randomly assigned to receive an intravitreal injection of bevacizumab (Avastin; Genentech, South San Francisco, CA), triamcinolone (Ophthalmos Pharmaceutical Industry, São Paulo-SP, Brazil), or their combination. The primary outcome was visual acuity (VA) at 6 months' follow-up. RESULTS: The average number of injections was 3.2 in the bevacizumab group, 2.4 in the combined group, and 2.1 in the triamcinolone group. All groups presented with improvements in VA (P < .001); however, no differences between groups were observed (P = .436). Mean reduction in central retinal thickness was statistically different only between the triamcinolone and bevacizumab groups (P < .015). CONCLUSION: Mono- or combination therapy was effective for DME treatment. No synergistic effects were observed; however, triamcinolone alone or a drug combination may reduce the number of injections required when compared to bevacizumab alone. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:734-740.].

Co-expressed miRNAs in gastric adenocarcinoma.

Co-expression networks may provide insights into the patterns of molecular interactions that underlie cellular processes. To obtain a better understanding of miRNA expression patterns in gastric adenocarcinoma and to provide markers that can be associated with histopathological findings, we performed weighted gene correlation network analysis (WGCNA) and compare it with a supervised analysis. Integrative analysis of target predictions and miRNA expression profiles in gastric cancer samples was also performed. WGCNA identified a module of co-expressed miRNAs that were associated with histological traits and tumor condition. Hub genes were identified based on statistical analysis and network centrality. The miRNAs 100, let-7c, 125b and 99a stood out for their association with the diffuse histological subtype. The 181 miRNA family and miRNA 21 highlighted for their association with the tumoral phenotype. The integrated analysis of miRNA and gene expression profiles showed the let-7 miRNA family playing a central role in the regulatory relationships.

Clustering of Expression Data in Chronic Lymphocytic Leukemia Reveals New Molecular Subdivisions.

Although the identification of inherent structure in chronic lymphocytic leukemia (CLL) gene expression data using class discovery approaches has not been extensively explored, the natural clustering of patient samples can reveal molecular subdivisions that have biological and clinical implications. To explore this, we preprocessed raw gene expression data from two published studies, combined the data to increase the statistical power, and performed unsupervised clustering analysis. The clustering analysis was replicated in 4 independent cohorts. To assess the biological significance of the resultant clusters, we evaluated their prognostic value and identified cluster-specific markers. The clustering analysis revealed two robust and stable subgroups of CLL patients in the pooled dataset. The subgroups were confirmed by different methodological approaches (non-negative matrix factorization NMF clustering and hierarchical clustering) and validated in different cohorts. The subdivisions were related with differential clinical outcomes and markers associated with the microenvironment and the MAPK and BCR signaling pathways. It was also found that the cluster markers were independent of the immunoglobulin heavy chain variable (IGVH) genes mutational status. These findings suggest that the microenvironment can influence the clinical behavior of CLL, contributing to prognostic differences. The workflow followed here provides a new perspective on differences in prognosis and highlights new markers that should be explored in this context.

Determination of the HER2 amplification status by in situ fluorescent hybridization and concordance with immunohistochemistry for breast cancer samples in Colombia / Determinación del estado de amplificación del Oncogén HER2 por hibridación in situ fluorecente y concordancia con el método de inmunohistoquímica en muestras de mujeres Colombianas con Cáncer de seno

Objectives: To determine the status of the HER2 amplification in Breast cancer performed in peripheral laboratories in Colombia by immunohistochemistry and its comparison with central laboratories and the FISH status. Methods: Four thousand one hundred and five cases referred for the determination of the HER2 status by FISH and/or IHQ to the Department of Pathology of the Fundacion Santa Fe were studied. The analysis included correlation between the IHQ HER2 score submitted by the peripheral laboratory (PL), the HER2 score emitted in the CL and the FISH studies performed in the central laboratory (CL). Results: Two thousand five hundred and eight HER2 IHQ studies were performed in the (CL), using the Dako Herceptest. With the following results: 68,2 % negative (0-1+); 16,4% indeterminate (2+); 15,3% 3+ and 2,3 % not adequate. 1360/ 1719 cases studied by FISH came from the (PL), and 329 (19,1%) from the (CL). Comparing the IHQ score emitted by the PL and the positive FISH status showed: 6/28 0+ were positive (21, 4%); 7/31 1+ (22, 5%); 397/1240 2+ (32, 8%) and 74/91 3+ (81, 3%). In the CL the results were 1/9 0+ (11,1%); 3/18 1+ (16,7%); 154/292 2+ (53%); and 9/9 3+ (100%). Only 1/4 negative cases (0/1+) was in house. Conclusion: The false negative rate (22%), and false positive results (18,7%), of the HER2 status performed by IHQ in peripheral laboratories in Colombia is unacceptable high as well as the inadequacy of tissue indicating that pre-analytical factors have to be improved in Colombia in order to get optimal results.

Objetivos: Determinar la correlación entre el estado de amplificación del oncogén HER2 en cáncer de seno por inmunohistoquímica y FISH, en laboratorios periféricos y en un laboratorio central de referencia en Colombia. Métodos: Se estudiaron 4105 casos referidos al Departamento de Patología de la Fundación Santa fe de Bogotá para la determinación del estado de amplificación del HER2 por FISH y/o IHQ. El análisis incluyó la correlación entre los scores del HER2 por IHQ en ambos laboratorios y los estudios de FISH realizados en el laboratorio central. Resultados: Dos mil quinientos ocho casos fueron estudiados para HER2 por IHQ en el LC (Herceptest de DAKO); 68.2% fueron negativos (score de 0-1+); 16.4% indeterminados (2+) y 15,3% positivos (3+); 2,3% fueron inadecuados. 1360 de 1689 casos estudiados por FISH (80.5%) provenían de LP, y 329 (19.5%) del LC. En los LP se encontró amplificación por FISH en: 6/28 casos catalogados por IHQ como 0+ (21.4%); 7/31 1+ (22.5%) ; 397/1210 2+ (2.8%) y 74/91 3+ (81.3%). En el LC se encontró amplificación por FISH en 1/9 casos catalogados por IHQ como 0+ (11.1%); 3/18 1+ (16.7%), 154/292 2+ (53%); y 10/10 3+ (100%) . Un de los 4 casos falsos negativos fue procesado en su totalidad en el LC. Conclusión: Los resultados falsos negativos (22.0%) y falsos positivos (18.7%) en el estado del HER2 determinado por IHQ en los LP son inaceptablemente altos en Colombia, indicando se requiere establecer mecanismos estrictos de control de calidad.

Determination of the HER2 amplification status by in situ fluorescent hybridization and concordance with immunohistochemistry for breast cancer samples in Colombia.

OBJECTIVES: To determine the status of the HER2 amplification in Breast cancer performed in peripheral laboratories in Colombia by immunohistochemistry and its comparison with central laboratories and the FISH status. METHODS: Four thousand one hundred and five cases referred for the determination of the HER2 status by FISH and/or IHQ to the Department of Pathology of the Fundacion Santa Fe were studied. The analysis included correlation between the IHQ HER2 score submitted by the peripheral laboratory (PL), the HER2 score emitted in the CL and the FISH studies performed in the central laboratory (CL). RESULTS: Two thousand five hundred and eight HER2 IHQ studies were performed in the (CL), using the Dako Herceptest. With the following results: 68.2 % negative (0-1+); 16,4% indeterminate (2+); 15.3% 3+ and 2.3 % not adequate. 1360/ 1719 cases studied by FISH came from the (PL), and 329 (19.1%) from the (CL). Comparing the IHQ score emitted by the PL and the positive FISH status showed: 6/28 0+ were positive (21. 4%); 7/31 1+ (22. 5%); 397/1240 2+ (32.8%) and 74/91 3+ (81. 3%). In the CL the results were 1/9 0+ (11.1%); 3/18 1+ (16.7%); 154/292 2+ (53%); and 9/9 3+ (100%). Only 1/4 negative cases (0/1+) was in house. CONCLUSION: The false negative rate (22%), and false positive results (18.7%), of the HER2 status performed by IHQ in peripheral laboratories in Colombia is unacceptable high as well as the inadequacy of tissue indicating that pre-analytical factors have to be improved in Colombia in order to get optimal results.

OBJETIVOS: Determinar la correlación entre el estado de amplificación del oncogén HER2 en cáncer de seno por inmunohistoquímica y FISH, en laboratorios periféricos y en un laboratorio central de referencia en Colombia. MÉTODOS: Se estudiaron 4105 casos referidos al Departamento de Patología de la Fundación Santa fe de Bogotá para la determinación del estado de amplificación del HER2 por FISH y/o IHQ. El análisis incluyó la correlación entre los scores del HER2 por IHQ en ambos laboratorios y los estudios de FISH realizados en el laboratorio central. RESULTADOS: Dos mil quinientos ocho casos fueron estudiados para HER2 por IHQ en el LC (Herceptest de DAKO); 68.2% fueron negativos (score de 0-1+); 16.4% indeterminados (2+) y 15,3% positivos (3+); 2,3% fueron inadecuados. 1360 de 1689 casos estudiados por FISH (80.5%) provenían de LP, y 329 (19.5%) del LC. En los LP se encontró amplificación por FISH en: 6/28 casos catalogados por IHQ como 0+ (21.4%); 7/31 1+ (22.5%) ; 397/1210 2+ (2.8%) y 74/91 3+ (81.3%). En el LC se encontró amplificación por FISH en 1/9 casos catalogados por IHQ como 0+ (11.1%); 3/18 1+ (16.7%), 154/292 2+ (53%); y 10/10 3+ (100%) . Un de los 4 casos falsos negativos fue procesado en su totalidad en el LC. CONCLUSIÓN: Los resultados falsos negativos (22.0%) y falsos positivos (18.7%) en el estado del HER2 determinado por IHQ en los LP son inaceptablemente altos en Colombia, indicando se requiere establecer mecanismos estrictos de control de calidad.

Cystoid macular edema in gyrate atrophy of the choroid and retina: a fluorescein angiography and optical coherence tomography evaluation.

PURPOSE: To analyze the importance f optical coherence tomography (OCT) to diagnose the cystoid macular edema in a case of gyrate atrophy. DESIGN: Observational case report. METHODS: A 12-year-old boy presenting with gyrate atrophy of the choroid and retina underwent ophthalmologic, clinical, and laboratory tests. RESULTS: Plasma ornithine level was 735 mumol/l. Fluorescein angiography showed bilateral hyperfluorescence involving the central region of the macula. Optical coherence tomography (OCT) disclosed bilateral intraretinal cysts areas of low reflectivity with occasional high-signal elements bridging the retinal layers and intraretinal thickening. CONCLUSIONS: Both fluorescein angiography and OCT were helpful to confirm the diagnosis of macular involvement as a complication of gyrate atrophy of the choroid and retina in a patient who presented without any clinical evidence of cystoid macular edema, except a decrease in visual acuity.

Visual electrophysiologic findings in patients from an extensive Brazilian family with Leber's hereditary optic neuropathy.

Leber's hereditary optic neuropathy (LHON) is a maternally inherited disease, associated with mitochondrial DNA (mtDNA) point mutations and characterized by bilateral, usually sequential, rapid loss of central vision. The purpose of this study was to investigate electrophysiologically a small cohort of members from an extensive Brazilian family affected by LHON. Pattern-reversal visual evoked potentials (PVEP), and full-field electroretinograms (ERG) were performed on the four index members, all carrying the 11778 homoplasmic mtDNA mutation. They were a 14-year-old recently affected male, his unaffected mother, and her two affected brothers. The three affected members all had bilateral profound visual loss with visual acuities that ranged from 20/250 to CF, cecocentral defects, and severe dyschromatopsia (by FM-100). The unaffected (carrier) female had normal visual acuities, visual fields and color discrimination. Severely prolonged P100 latencies and decreased N75-P100 peak amplitudes were found in pattern-reversal VEPs for three affected members. Normal PVEP responses were found in the carrier female. Rod and cone ERG responses were normal in two affected members, but both the carrier mother and her affected son showed reduced peak-to-peak amplitude for single-flash cone response and 30 Hz flicker, with normal b-wave implicit times. Thus, optic nerve function, evaluated by PVEP, was severely reduced in LHON affected members and normal in the carrier female. However, reduced ERG cone responses suggest that LHON can also affect retinal elements, even in the absence of fundus and other clinical changes that constitute the full and classical expression of LHON.

Intravitreal triamcinolone in the treatment of serous retinal detachment in Vogt-Koyanagi-Harada syndrome.

PURPOSE: To report the use of intravitreal injection of triamcinolone acetonide during the acute phase of Vogt-Koyanagi-Harada disease. DESIGN: Prospective interventional case series. METHODS: Three eyes from two patients at the acute phase of Vogt-Koyanagi-Harada disease with serous retinal detachments were treated with a 4-mg intravitreal injection of triamcinolone acetonide. The following variables were evaluated: visual acuity, intraocular pressure, and height of the serous retinal detachment using optical coherence tomography. RESULTS: The optical coherence tomography images showed a marked decrease in the retinal detachment in the first week after the injection with subsequent return to normal retinal thickness in all eyes. CONCLUSIONS: Intravitreal triamcinolone acetonide provides short-term improvement in visual acuity and serous retinal detachments associated with Vogt-Koyanagi-Harada disease. These findings should be followed by future studies to evaluate long-term effects.

Photodynamic therapy with verteporfin for subfoveal choroidal neovascularization in best disease.

PURPOSE: To describe the effects of photodynamic therapy using verteporfin for the treatment of subfoveal choroidal neovascularization (CNV) in Best vitelliform macular dystrophy. DESIGN: Interventional case report. METHODS: A 43-year-old patient with confirmed Best vitelliform macular dystrophy complicated with subfoveal CNV received a single photodynamic therapy session with verteporfin. The patient was prospectively followed with fluorescein angiography and optical coherence tomography. RESULTS: A regression of the neovascular lesion and resolution of the exudative manifestations was observed 3 weeks after treatment; at that time, visual acuity had improved from 20/60 to 20/25. Optical coherence tomography disclosed restoration of normal macular architecture due to fluid resolution and lesion contraction. Up to 2 years from this single treatment, no further change was observed. CONCLUSIONS: Regression of CNV and resolution of subretinal hemorrhage as well as exudative manifestations occurred after photodynamic therapy with verteporfin. Verteporfin therapy may be a viable treatment for subfoveal neovascular lesions in Best vitelliform macular dystrophy.