Focal-to-bilateral tonic-clonic seizures and High-grade CMV-infection are poor survival predictors in Tumor-related Epilepsy Adult-type diffuse gliomas-A single-center study and literature review.

Introduction: Previous studies have reported a correlation between a high-grade CMV-infection and an unfavorable prognosis in glioblastoma (GB). Coversely, epilepsy has been associated with a more favorable outcome in GB patients. Despites epilepsy and CMV share similar molecular mechanisms in GB tumoral microenvironment, the correlation between Tumor-Related-Epilepsy (TRE) and CMVinfection remains unexplored. The aim of our study is to examine the correlation between the dregree of CMV infection and seizure types on the survival of TRE Adult-type-diffuse-glioma. To achieve this objective, we conducted a comprehensive literature review to assess our results regarding previous publications. Methods: We conducted a retrospective-observational study on TRE Adult-type-diffuse-gliomas treated at a single center in Mexico from 2010 to 2018. Tumor tissue and cDNA were analyzed by immunochemistry (IHC) for CMV (IE and LA antigens) at the Karolinska Institute in Sweden, and RT-PCR for CMV-gB in Torreon Mexico, respectively. Bivariate analysis (X2-test) was performed to evaluate the association between subtypes of Adult-type-diffuse-glioma (IDH-mut grade 4 astrocytoma vs. IDH-wt glioblastoma) and the following variables: type of hemispheric involvement (mesial vs. neocortical involvement), degree of CMV infection (<25%vs. >25% infected-tumoral cells) and seizure types [Focal awareness, focal impaired awareness, and FBTCS]. Kaplan Meier and Cox analyses were performed to determine the risk, p < 0.05 was considered statistically significant. Results: Sixty patients with TRE Adult type diffuse gliomas were included (80% IDH-wt glioblastoma and 20% IDH-mut grade 4astrocytomas). The mean age was 61.5 SD ± 18.4, and 57% were male. Fifty percent of the patients presented with mesial involvement of the hemysphere. Seizure types included focal awareness (15%), focal impaired awareness (43.3%), and FBTCS (41.7%). Ninety percent of cases were treated with Levetiracetam and 33.3% presented Engel-IA postoperative seizure control. More than 90% of samples were positive for CMV-immunohistochemistry (IHC). However, all cDNA analyzed by RT-PCR return negative results. The median of overall survival (OS) was 15 months. High-grade CMV-IE infection (14 vs. 25 months, p<0.001), mesial involvement (12 vs. 18 months, p<0.001), and FBTCS were associated with worse OS (9 vs.18 months for non-FBTCS). Multivariate analysis demonstrated that high-grade CMV infection (HR = 3.689, p=0.002) and FBTCS (HR=7.007, p<0.001) were independent unfavorable survival factors. Conclusions: CMV induces a proinflammatory tumoral microenvironment that contributes to the developmet of epilepsy. Tumor progression could be associated not only with a higher degree of CMV infection but also to epileptogenesis, resulting in a seizure phenotype chracterized by FBTCS and poor survival outcomes. This study represents the first survival analysis in Latin America to include a representative sample of TRE Adult-type diffuse gliomas considering CMV-infection-degree and distinguishing features (such as FBTCS) that might have potential clinical relevance in this group of patients. Further prospective studies are required to validate these results.

Efficacy of cabergoline therapy in patients with non-functioning pituitary adenomas: A single center clinical experience

ABSTRACT Objective: To evaluate the response to cabergoline (CBG) treatment in patients with non-functioning pituitary adenomas (NFPA). Subjects and methods: Retrospective, single tertiary care center study. A total of 44 patients were treated with 3 mg/week of CBG, 32 after surgical treatment (transsphenoidal surgery [TSS] in 27 and TC in 5 patients) and 12 as primary therapy. Mean age was 59.2 ± 12 years and 23 (52.2%) were women. Response to therapy was ascertained by serial magnetic resonance imaging. The median duration of CBG therapy was 30 months (IQR 24-48). Response to CBG therapy was defined as a greater than 20% reduction in tumor size and volume. Results: A significant reduction in tumor size was documented in 29 patients (66%), whereas in 11 patients (25%) the tumor increased in size and in 4 (9%), it remained stable. Significant tumor shrinkage was documented in 4 (33.3%) of 12 patients treated primarily and in 23 (71.8%) of those treated secondarily. The three-year progression-free survival was 0.61. Conclusion: Cabergoline therapy is effective in reducing tumor growth in over two thirds of patients with NFPA, however 16% of patients will escape to this beneficial effect and will require alternative forms of treatment to halt tumor progression.

Efficacy of cabergoline therapy in patients with non-functioning pituitary adenomas: A single center clinical experience.

Introduction: To evaluate the response to cabergoline (CBG) treatment in patients with non-functioning pituitary adenomas (NFPA). Subjects and methods: Retrospective, single tertiary care center study. A total of 44 patients were treated with 3 mg/week of CBG, 32 after surgical treatment (transsphenoidal surgery [TSS] in 27 and TC in 5 patients) and 12 as primary therapy. Mean age was 59.2 ± 12 years and 23 (52.2%) were women. Response to therapy was ascertained by serial magnetic resonance imaging. The median duration of CBG therapy was 30 months (IQR 24-48). Response to CBG therapy was defined as a greater than 20% reduction in tumor size and volume. Results: A significant reduction in tumor size was documented in 29 patients (66%), whereas in 11 patients (25%) the tumor increased in size and in 4 (9%), it remained stable. Significant tumor shrinkage was documented in 4 (33.3%) of 12 patients treated primarily and in 23 (71.8%) of those treated secondarily. The three-year progression-free survival was 0.61. Conclusion: Cabergoline therapy is effective in reducing tumor growth in over two thirds of patients with NFPA, however 16% of patients will escape to this beneficial effect and will require alternative forms of treatment to halt tumor progression.

Shear-wave elastography as a tool in the assessment of thyroid nodules.

INTRODUCTION: Shear-wave elastography (SWE) has been shown to be predictive of malignancy in thyroid nodules. OBJECTIVE: To determine, by SWE, the stiffness cutoff point with the highest specificity and sensitivity to detect thyroid nodules that require surgery. METHODS: Cross-sectional study of ultrasonographically-evaluated patients for thyroid nodules over a period of three years; the TI-RADS classification system was used, and nodule stiffness was determined by SWE. Histopathological specimens were classified using the Bethesda system, and the stiffness cutoff point with the highest specificity and sensitivity was obtained using ROC curves. RESULTS: Forty-one percent of the nodules were classified as TI-RADS 5, and 59 %, as TI-RADS 1-4. In TI-RADS 5 nodules, median stiffness of those in Bethesda system IV-VI categories was 35.9 kPa; in nodules with TI-RADS 1-4, 21.6 kPa. In TI-RADS 5 nodules, a cutoff point > 32.5 kPa had a specificity of 75 % and sensitivity of 57 % to detect those requiring surgery; in TI-RADS 1 to 4 nodules, a cutoff point of 21.5 kPa had a specificity of 63 % and sensitivity of 51 %. CONCLUSION: SWE-determined stiffness is useful to detect nodules that require surgical evaluation.

INTRODUCCIÓN: La elastografía por ondas de corte (SWE) ha demostrado ser predictiva de malignidad en nódulos tiroideos. OBJETIVO: Determinar mediante SWE, el punto de corte de la rigidez con mayor especificidad y sensibilidad para detectar nódulos tiroideos que requieren cirugía. MÉTODOS: Estudio transversal de pacientes con nódulos tiroideos evaluados ultrasonográficamente en un periodo de tres años; se empleó la clasificación TI-RADS y mediante SWE se determinó la rigidez de los nódulos. Con el sistema Bethesda se clasificaron las muestras histopatológicas y mediante curva ROC se obtuvo el punto de corte de la rigidez con mayor especificidad y sensibilidad. RESULTADOS: 41 % de los nódulos fue TI-RADS 5 y 59 %, TI-RADS 1-4. En los TI-RADS 5, la mediana de rigidez de los nódulos con categoría IV-VI del sistema Bethesda fue de 35.9 kPa y en los nódulos con TI-RADS 1-4, 21.6 kPa. En los nódulos TI-RADS 5, la rigidez > 32.5 kPa tuvo especificidad de 75 % y sensibilidad de 57 % para detectar los que requieren cirugía; en los TI-RADS 1-4, el valor de corte de 21.5 kPa tuvo especificidad de 63 % y sensibilidad de 51 %. CONCLUSIÓN: La rigidez determinada por SWE es útil para detectar nódulos que requerirán exploración quirúrgica.

Elastografía por ondas de corte como herramienta en la evaluación de los nódulos tiroideos / Shear-wave elastography as a tool in the assessment of thyroid nodules

Resumen Introducción: La elastografía por ondas de corte (SWE) ha demostrado ser predictiva de malignidad en nódulos tiroideos. Objetivo: Determinar mediante SWE, el punto de corte de la rigidez con mayor especificidad y sensibilidad para detectar nódulos tiroideos que requieren cirugía. Métodos: Estudio transversal de pacientes con nódulos tiroideos evaluados ultrasonográficamente en un periodo de tres años; se empleó la clasificación TI-RADS y mediante SWE se determinó la rigidez de los nódulos. Con el sistema Bethesda se clasificaron las muestras histopatológicas y mediante curva ROC se obtuvo el punto de corte de la rigidez con mayor especificidad y sensibilidad. Resultados: 41 % de los nódulos fue TI-RADS 5 y 59 %, TI-RADS 1-4. En los TI-RADS 5, la mediana de rigidez de los nódulos con categoría IV-VI del sistema Bethesda fue de 35.9 kPa y en los nódulos con TI-RADS 1-4, 21.6 kPa. En los nódulos TI-RADS 5, la rigidez > 32.5 kPa tuvo especificidad de 75 % y sensibilidad de 57 % para detectar los que requieren cirugía; en los TI-RADS 1-4, el valor de corte de 21.5 kPa tuvo especificidad de 63 % y sensibilidad de 51 %. Conclusión: La rigidez determinada por SWE es útil para detectar nódulos que requerirán exploración quirúrgica.

Abstract Introduction: Shear-wave elastography (SWE) has been shown to be predictive of malignancy in thyroid nodules. Objective: To determine, by SWE, the stiffness cutoff point with the highest specificity and sensitivity to detect thyroid nodules that require surgery. Methods: Cross-sectional study of ultrasonographically-evaluated patients for thyroid nodules over a period of three years; the TI-RADS classification system was used, and nodule stiffness was determined by SWE. Histopathological specimens were classified using the Bethesda system, and the stiffness cutoff point with the highest specificity and sensitivity was obtained using ROC curves. Results: Forty-one percent of the nodules were classified as TI-RADS 5, and 59 %, as TI-RADS 1-4. In TI-RADS 5 nodules, median stiffness of those in Bethesda system IV-VI categories was 35.9 kPa; in nodules with TI-RADS 1-4, 21.6 kPa. In TI-RADS 5 nodules, a cutoff point > 32.5 kPa had a specificity of 75 % and sensitivity of 57 % to detect those requiring surgery; in TI-RADS 1 to 4 nodules, a cutoff point of 21.5 kPa had a specificity of 63 % and sensitivity of 51 %. Conclusion: SWE-determined stiffness is useful to detect nodules that require surgical evaluation.

Erratum to "From ACTH-Dependent to ACTH-Independent Cushing's Syndrome from a Malignant Mixed Corticomedullary Adrenal Tumor: Potential Role of Embryonic Stem Cells".

[This corrects the article DOI: 10.1155/2020/4768281.].

From ACTH-Dependent to ACTH-Independent Cushing's Syndrome from a Malignant Mixed Corticomedullary Adrenal Tumor: Potential Role of Embryonic Stem Cells.

OBJECTIVE: To report the immunohistochemical and molecular evaluation of a patient with ectopic ACTH syndrome (EAS) from a MCAT which has single cells with features of both 96 medullary and cortical differentiation. Case Description and Methods. A 16-year-old woman presented with severe EAS and a large right MCAT composed of ACTH-secreting cells resembling pheochromocytoma and another lineage similar to adrenal carcinoma. Immunohistochemistry (IHC) showed positivity for medullary (ACTH, chromogranin A, synaptophysin, and PS-100) and epithelial components (inhibin, melan-A, and calretinin). Embryonic stem cell markers were evaluated using RT/PCR and immunofluorescence. After initial surgery, the tumor recurred shifting to rapidly progressive ACTH-independent liver metastasis. RESULTS: Histopathology and IHC revealed two distinct and intermingled cellular patterns, while some cells immunostained for both medullary and cortical markers. Demonstration of all stem cell biomarkers by RT/PCR and immunofluorescence was predominantly localized to the nucleus, whereas SOX2 immunoreactivity was evident in the cytoplasm as well. CONCLUSION: The expression of cancer stem cell biomarkers points towards the involvement of primitive embryonic cells as the origin of this neoplasm and maybe to the clinically aggressive and biochemically changing behavior.

Primary cystic neuroendocrine tumor of the liver: case report / Tumor neuroendócrino quístico primario de hígado: reporte de un caso

Background: 85% of neuroendocrine tumors (NET) originate in the gastrointestinal tract, which is why their primary hepatic location is very rare; NETs most frequently cause metastases to the liver; so when diagnosed, a hepatic NET is considered initially metastatic. Diagnosis of primary hepatic neuroendocrine tumors (PHNET) should be performed by excluding extrahepatic NETs and through histological confirmation. The objective of this article is to present a case of PHNET. Clinical case: 75-year-old male patient, who presented asthenia, adynamia, abdominal pain in the right hypochondrium, six-month weight loss, with a right subcostal palpable tumor. Imaging studies reported a lesion in the right hepatic lobe, multilobulated, heterogeneous, with poorly defined margins and with cystic areas. It was performed diagnostic laparotomy and then a hepatic tumorectomy, whose product measured 16.0 x 10.0 x 6.5 cm, with two cystic cavities of 13.2 and 11.5 cm of hematic content. Microscopically, cells with neuroendocrine differentiation, with positive immunoreactivity to chromogranin were observed. It was diagnosed well-differentiated neuroendocrine neoplasm, with cystic degeneration. Conclusions: Even though it is excluded a NET from an extrahepatic primary site, the tumor etiology of an important proportion of patients with PHNET will be due to an unknown primary tumor that will become apparent over time; hence, the need to follow up as long as possible.

Introducción: 85% de los tumores neuroendocrinos (TNE) se originan del tracto gastrointestinal, su localización hepática primaria muy rara; los TNE con mayor frecuencia causan metástasis al hígado; por esto, cuando se diagnóstica un TNE hepático es considerado inicialmente metastásico. El diagnóstico de tumor neuroendocrino primario de hígado (TNEPH) debe realizarse mediante la exclusión de tumores neuroendócrinos extrahepáticos y la confirmación histológica. El objetivo de este artículo es presentar un caso con TNEHP. Caso clínico: paciente de sexo masculino, de 75 años de edad, quien presentó astenia, adinamia, dolor abdominal en hipocondrio derecho y pérdida de peso de 6 meses de evolución, con tumor palpable subcostal derecho. Los estudios de imagen reportaron lesión en lóbulo hepático derecho, multilobulada, márgenes mal definidos, heterogénea y con áreas quísticas. Se realizó laparotomía diagnóstica y tumorectomía hepática que midió 16.0 x10.0 x 6.5 cm, con dos cavidades quísticas de 13.2 y 11.5 cm de contenido hemático. Microscópicamente se observaron células con diferenciación neuroendócrina, inmunoreactivas a cromogranina. Se estableció el diagnóstico de neoplasia neuroendócrina bien diferenciada, con degeneración quística. Conclusiones: aunque se excluya un TNE de sitio primario extrahepático, la etiología tumoral de una proporción considerable de pacientes con TNEPH será a causada por un tumor primario no conocido que se hará evidente con el tiempo; de ahí la necesidad de hacer seguimiento el máximo tiempo posible.

Tumor-associated macrophages and angiogenesis: a statistical correlation that could reflect a critical relationship in ameloblastoma.

Neoplasm growth is determined not only by the tumor cells themselves, but also by the tumor microenvironment. Increased densities of macrophages and activation of angiogenesis have been identified as common events in the progression of several neoplasms. Ameloblastoma is one of the most frequent odontogenic tumors and an excellent model for the study of neoplasm progression due to the different clinical variants that it exhibits. Here, by immunohistochemical studies using antibodies against CD68 and CD34, we evaluated the density of macrophages and microvessels associated to 45 paraffin-embedded ameloblastomas. In solid/multicystic ameloblastoma (SMA), we observed significantly higher densities of both macrophages and microvessels than in unicystic (UA) and desmoplastic (DA) ameloblastomas. Likewise, higher densities of macrophages and microvessels were found in UA than in DA. Furthermore, a predominance of intratumoral and peritumoral macrophage infiltrates was seen in SMA, while in UA, both macrophages and microvessels were also detected in the wall of the cysts. In contrast, DA had scant macrophages and microvessels, mainly situated distant from tumoral cells. In addition, a high correlation between macrophage and microvessel densities was observed in the samples (r=0.9623). Our results suggest that these two tumor microenvironmental elements could have an important role during ameloblastoma progression.