Small adrenal incidentaloma becoming an aggressive adrenocortical carcinoma in a patient carrying a germline APC variant.

PURPOSE: Recent guidelines on adrenal incidentalomas suggested in patients with an indeterminate adrenal mass and no significant hormone excess that follow up with a repeat noncontrast CT or MRI after 6-12 months may be an option. METHODS: We report the case of a 32-year-old woman who presented with a 2.9 × 1.9 cm left adrenal incidentaloma that was stable in size for 4 years. Ten years later the left adrenal mass was a stage IV adrenocortical carcinoma (ACC). RESULTS: In 2006, a 32-year-old French Canadian woman was referred to endocrinology for a left 2.9 × 1.9 cm incidentally discovered adrenal mass (31 HU). She had normal hormonal investigation. The patient was followed with adrenal imaging and hormonal investigation yearly for 4 years and the lesion stayed stable in size over the 4 years. Ten years later, in 2016, the patient presented with renal colic. Urological CT unexpectedly revealed that the left adrenal mass was now measuring 9 × 8.2 cm and 2 new hepatic lesions were found. Biochemical workup demonstrated hypercorticism and hyperandrogenemia: plasma cortisol after 1 mg overnight DST of 476 nmol/L and DHEA-S of 14.0 µmol/L (N 0.9-6.5). Twenty-four hour urine steroid profiling was consistent with an adrenocortical carcinoma (ACC) co-secreting cortisol, androgens and glucocorticoid precursors. The diagnosis of ACC with hepatic ACC metastases was confirmed at histology. Following genetic analysis, germline heterozygous variant of uncertain significance (VUS) was identified in the exon 16 of the APC gene (c.2414G > A, p.Arg805Gln). Immunohistochemical staining's of the ACC was positive for IGF-2 and cytoplasmic/nuclear ß-catenin staining. CONCLUSIONS: This case illustrates that (1) small adrenal incidentaloma stable in size may evolve to ACC and (2) better genetic characterization of these patients may eventually give clues on this unusual evolution.

Características clínico-epidemiológicas del queratocono en la edad pediátrica / Clinical-epidemiological characteristics of keratoconus in the pediatric age

Introducción: el queratocono se presenta como una ectasia corneal, típica en el adolescente y el adulto joven, que afecta la morfología corneal y, por consiguiente, la visión.Objetivo: describir las características clínico-epidemiológicas del queratocono en la edad pediátrica en la provincia Ciego de Ávila.Método: se realizó un estudio observacional descriptivo transversal, el universo estuvo constituido por 86 ojos de 56 niños diagnosticados con queratocono en la consulta de ectasia corneal del Centro Oftalmológico de Ciego de Ávila en el bienio febrero de 2014 a enero de 2016. Se analizaron variables como: edad, sexo, síntomas, signos, agudeza visual sin corrección y mejor corregida, defecto refractivo, valores paquimétricos, queratométricos, índices topográficos y grados de evolución del queratocono.Resultados: predominaron el sexo masculino y el grupo de edades de 14 a 17 años. El síntoma más frecuente fue la visión borrosa y el signo anillo de Fleischer. La mayoría de los pacientes presentaron una agudeza visual sin corrección menor de 0,2, con una mejoría de más de 0,5 una vez corregida. El astigmatismo miópico compuesto predominó sobre el resto de los defectos refractivos. Los valores paquimétricos más frecuentes oscilaron entre 501 µm y 550 µm, y la queratometría hasta 48 dioptrías. El índice de sector diferenciado fue el más alterado en la topografía corneal y prevaleció el queratocono grado I.Conclusiones: el queratocono es frecuente entre los adolescentes masculinos, siendo la topografía corneal un examen clave para el diagnóstico de la enfermedad en estadios iniciales(AU)

Introduction: keratoconus appears as a corneal ectasia, typical in adolescents and young adults, which affects corneal morphology and vision.Objective: to describe the clinical and epidemiological characteristics of keratoconus in the pediatric age in Ciego de Ávila province.Method: a transversal descriptive observational study was carried out, the universe was constituted by 86 eyes of 56 children diagnosed with keratoconus in the corneal ectasia consultation of the Ophthalmological Center of Ciego de Ávila in the biennium February 2014 to January 2016. Variables were analyzed such as: age, sex, symptoms, signs, visual acuity without correction and better corrected, refractive defect, pachymetric, keratometric values, topographic indexes and degrees of keratoconus evolution.Results: male sex prevailed and the age group of 14 to 17 years old. The most frequent symptom was blurred vision and Fleischer's ring sign. The majority of patients presented a visual acuity without correction less than 0,2, with an improvement over 0,5 once corrected. The compound myopic astigmatism predominated over the rest of the refractive defects. The most frequent pachymetric values oscillated between 501 μm and 550 μm, and the keratometry up to 48 diopters. The differentiated sector index was the most altered in the corneal topography and keratoconus grade I prevailed.Conclusions: keratoconus is frequent among male adolescents, and corneal topography is a key test for the diagnosis of the disease in the early stages(AU)

Multiple criteria optimization joint analyses of microarray experiments in lung cancer: from existing microarray data to new knowledge.

Microarrays can provide large amounts of data for genetic relative expression in illnesses of interest such as cancer in short time. These data, however, are stored and often times abandoned when new experimental technologies arrive. This work reexamines lung cancer microarray data with a novel multiple criteria optimization-based strategy aiming to detect highly differentially expressed genes. This strategy does not require any adjustment of parameters by the user and is capable to handle multiple and incommensurate units across microarrays. In the analysis, groups of samples from patients with distinct smoking habits (never smoker, current smoker) and different gender are contrasted to elicit sets of highly differentially expressed genes, several of which are already associated to lung cancer and other types of cancer. The list of genes is provided with a discussion of their role in cancer, as well as the possible research directions for each of them.

An Optimization-Driven Analysis Pipeline to Uncover Biomarkers and Signaling Paths: Cervix Cancer.

Establishing how a series of potentially important genes might relate to each other is relevant to understand the origin and evolution of illnesses, such as cancer. High-throughput biological experiments have played a critical role in providing information in this regard. A special challenge, however, is that of trying to conciliate information from separate microarray experiments to build a potential genetic signaling path. This work proposes a two-step analysis pipeline, based on optimization, to approach meta-analysis aiming to build a proxy for a genetic signaling path.

DNA damage signaling and apoptosis in preinvasive tubal lesions of ovarian carcinoma.

OBJECTIVE: High-grade serous ovarian cancer (HGSC) is the most life-threatening gynecological malignancy despite surgery and chemotherapy. A better understanding of the molecular basis of the preinvasive stages might be helpful in early detection and diagnosis. Genetic instability is 1 of the characteristics shared by most human cancers, and its level is variable through precancerous lesions to advanced cancer. Because DNA damage response (DDR) has been described as 1 of the first phases in genomic instability, we investigated the level of DDR activation and the apoptosis pathway in serous tubal intraepithelial carcinoma (STIC), the potential precursor of HGSC. METHODS/MATERIALS: A tissue microarray including 21 benign fallopian tubes, 21 STICs, 17 HGSCs from patients with STICs (associated ovarian cancer [AOC]) from the same individuals, and 30 HGSCs without STICs (non-AOC) was used in this study.Immunohistochemistry was performed to evaluate the level of DDR proteins (pATM, pChk2, γH2AX, 53BP1, and TRF2), apoptosis proteins (Bcl2, BAX, and BIM), and cyclin E. RESULTS: The expression of all DDR proteins increased from benign fallopian tubes to STICs. The level of expression of pATM, pChk2, γH2AX, and TRF2 was also increased in STICs in comparison with AOC. BAX, BIM, and cyclin E expressions were high in STICs, whereas Bcl2 expression was low. Immunohistochemical profiles of AOC and non-AOC were also different. CONCLUSIONS: These results suggest an activation of the DDR and apoptosis pathways in STICs, indicating that genomic instability may occur early in the precancerous lesions of HGSC.

Derivation and characterization of matched cell lines from primary and recurrent serous ovarian cancer.

BACKGROUND: Cell line models have proven to be effective tools to investigate a variety of ovarian cancer features. Due to the limited number of cell lines, particularly of the serous subtype, the heterogeneity of the disease, and the lack of cell lines that model disease progression, there is a need to further develop cell line resources available for research. This study describes nine cell lines derived from three ovarian cancer cases that were established at initial diagnosis and at subsequent relapse after chemotherapy. METHODS: The cell lines from three women diagnosed with high-grade serous ovarian cancer (1369, 2295 and 3133) were derived from solid tumor (TOV) and ascites (OV), at specific time points at diagnosis and relapse (R). Primary treatment was a combination of paclitaxel/carboplatin (1369, 3133), or cisplatin/topotecan (2295). Second line treatment included doxorubicin, gemcitabine and topotecan. In addition to molecular characterization (p53, HER2), the cell lines were characterized based on cell growth characteristics including spheroid growth, migration potential, and anchorage independence. The in vivo tumorigenicity potential of the cell lines was measured. Response to paclitaxel and carboplatin was assessed using a clonogenic assay. RESULTS: All cell lines had either a nonsense or missense TP53 mutations. The ability to form compact spheroids or aggregates was observed in six of nine cell lines. Limited ability for migration and anchorage independence was observed. The OV3133(R) cell line, formed tumors at subcutaneous sites in SCID mice. Based on IC50 values and dose response curves, there was clear evidence of acquired resistance to carboplatin for TOV2295(R) and OV2295(R2) cell lines. CONCLUSION: The study identified nine new high-grade serous ovarian cancer cell lines, derived before and after chemotherapy that provides a unique resource for investigating the evolution of this common histopathological subtype of ovarian cancer.

Cirugía Corneal con Láser Excímer en pacientes adultos con ambliopía refractiva / Corneal surgery with Excimer Laser in adult patients with amblyopia refractive

Introducción: La visión es uno de los sentidos más necesarios para el desarrollo psico-social del ser humano, al encontrarse afectada, genera dificultades en el ámbito personal y social del individuo y su familia. En la consulta de Cirugía Refractiva Corneal del Centro Oftalmológico de Ciego de Ávila se ha constatado una apreciable incidencia de pacientes adultos con ambliopía de causa refractiva. Método: Sobre los resultados obtenidos a partir de la corrección quirúrgica con Láser Excímer del defecto refractivo en estos pacientes, se realiza este estudio. El universo lo conformó la totalidad de los pacientes operados, se utilizó la técnica LASIK en el Servicio de Cirugía corneal con Láser Excímer; la muestra estuvo compuesta por los pacientes operados con el diagnóstico de ambliopía de causa refractiva, a los cuales se les realizó un total de 86 cirugías. Resultado: Se constata que los pacientes que no usaron corrección refractiva en la infancia fueron los de mayor incidencia en el estudio, así como los que padecen de ambliopía anisometrópica y los pertenecientes a grupos de edad más jóvenes. El astigmatismo miópico compuesto fue el defecto refractivo predominante en los pacientes estudiados. En el postoperatorio se obtuvo una evolución satisfactoria de la agudeza visual sin corrección y la agudeza visual mejor corregida. Conclusiones: La corrección refractiva con Láser puede llegar a ser una alternativa de tratamiento para estos pacientes, proporcionar un adecuado desempeño laboral y social, así como un incremento de la calidad de vida(AU)

Introduction: Vision is one of the most necessary senses for the psico-social development of the human being, when is affected, it generates social and personal difficulties in a person. In the consultation of Corneal Refractive Surgery from Ciego de Avila Ophthalmological Center an appreciable incidence of adult patients with refractive amblyopia has been verified. Method: This study is carried out on the results obtained starting from the surgical correction with Laser Excimer of the refractive defect.Technical LASIK was applied in all the patients in the corneal surgery service with Excímer Laser.The sample was composed by operated patients with amblyopia of refractive cause, to which a total of 86 surgeries was carried out to them. Results: It is verified that those patients who didn't use refractive correction in the childhood were those of more incidence in the study, as well as those that suffer of anisometropic amblyopia and those who are younger. The composed myopic astigmatism was the predominant refractive defect in the studied patients. In the postoperative it was obtained a satisfactory evolution of visual acuity without correction and best corrected visual acuity. Conclusions: The refractive correction with Laser can reach to be an alternative treatment for these patients, providing an appropriate labor Performance, as well as an increment of the quality of life(AU)

Cirugía Corneal con Láser Excímer en pacientes adultos con ambliopía refractive / Corneal surgery with excimer laser in adult patients with amblyopia refractive

Introducción: La visión es uno de los sentidos más necesarios para el desarrollo psico-social del ser humano, al encontrarse afectada, genera dificultades en el ámbito personal y social del individuo y su familia. En la consulta de Cirugía Refractiva Corneal del Centro Oftalmológico de Ciego de Ávila se ha constatado una apreciable incidencia de pacientes adultos con ambliopía de causa refractiva. Método: Sobre los resultados obtenidos a partir de la corrección quirúrgica con Láser Excímer del defecto refractivo en estos pacientes, se realiza este estudio. El universo lo conformó la totalidad de los pacientes operados, se utilizó la técnica LASIK en el Servicio de Cirugía corneal con Láser Excímer; la muestra estuvo compuesta por los pacientes operados con el diagnóstico de ambliopía de causa refractiva, a los cuales se les realizó un total de 86 cirugías. Resultado: Se constata que los pacientes que no usaron corrección refractiva en la infancia fueron los de mayor incidencia en el estudio, así como los que padecen de ambliopía anisometrópica y los pertenecientes a grupos de edad más jóvenes. El astigmatismo miópico compuesto fue el defecto refractivo predominante en los pacientes estudiados. En el postoperatorio se obtuvo una evolución satisfactoria de la agudeza visual sin corrección y la agudeza visual mejor corregida. Conclusiones: La corrección refractiva con Láser puede llegar a ser una alternativa de tratamiento para estos pacientes, proporcionar un adecuado desempeño laboral y social, así como un incremento de la calidad de vida.

Introduction: Vision is one of the most necessary senses for the psico-social development of the human being, when is affected, it generates social and personal difficulties in a person. In the consultation of Corneal Refractive Surgery from Ciego de Avila Ophthalmological Center an appreciable incidence of adult patients with refractive amblyopia has been verified. Method: This study is carried out on the results obtained starting from the surgical correction with Laser Excimer of the refractive defect.Technical LASIK was applied in all the patients in the corneal surgery service with Excímer Laser.The sample was composed by operated patients with amblyopia of refractive cause, to which a total of 86 surgeries was carried out to them. Results: It is verified that those patients who didn't use refractive correction in the childhood were those of more incidence in the study, as well as those that suffer of anisometropic amblyopia and those who are younger. The composed myopic astigmatism was the predominant refractive defect in the studied patients. In the postoperative it was obtained a satisfactory evolution of visual acuity without correction and best corrected visual acuity. Conclusions: The refractive correction with Laser can reach to be an alternative treatment for these patients, providing an appropriate labor Performance, as well as an increment of the quality of life.