Stromal osseous metaplasia in urothelial carcinoma of the bladder: An unusual and challenging feature. A case report / Carcinoma urotelial de vejiga con metaplasia ósea estromal: una característica inusual y desafiante. Presentación de un caso

A 62-year-old male presented with pain and haematuria starting 3 months before. The computed tomography showed focal and mural bladder thickening with ureteropelvic dilatation. The following transurethral bladder resection revealed a high-grade muscle-invasive urothelial carcinoma. In the subsequent cystoprostatectomy we found the same tumour, but adding focal tumour-associated stromal osseous metaplasia. Ossifying metaplasia is an extremely rare feature in urothelial carcinoma, with a few reported cases and represents a diagnostic challenge, mimicking radiotherapy-induced sarcoma or sarcomatoid carcinoma. (AU)

Varón de 62 años que consulta por dolor y hematuria desde hace 3 meses. En la tomografía computarizada se observó un engrosamiento focal y mural de la vejiga con dilatación ureteropélvica. La resección vesical transuretral reveló un carcinoma urotelial infiltrante de alto grado músculo-invasivo. En la cistoprostatectomía posterior encontramos el mismo tumor, pero añadiendo focos de metaplasia ósea estromal asociada al tumor. La metaplasia osificante es una característica extremadamente rara en el carcinoma urotelial, con algunos casos informados, y representa un desafío diagnóstico, ya que simula un sarcoma inducido por radioterapia o un carcinoma sarcomatoide. (AU)

Rspo2-LGR4 exacerbates hepatocellular carcinoma progression via activation of Wnt/b-catenin signaling pathway / Rspo2-LGR4 agrava la progresión del carcinoma hepatocelular al activar la vía de señalización Wnt/beta-catenina

Background: The leucine-rich repeat-containing G-protein-coupled receptor 4 (LGR4) plays an important role in stem cell differentiation, organ development and cancer. Whether LGR4 affects the progression of hepatocellular carcinoma (HCC) remains unknown. This study aimed to reveal the role of LGR4 in HCC. Methods: Clinical samples of HCC were collected to assess the expression of LGR4 and its correlation with patients’ clinical characteristics. The expression level of LGR4 in HCC cells was altered by pharmacological and genetic methods, and the role of LGR4 in HCC progression was analyzed by in vivo and in vitro assays. HCC was induced by diethylnitrosamine (DEN) and carbon tetrachloride (CCl4) in wild-type and LGR4 deficient mice, the effect of LGR4 on HCC was examined by histopathological evaluation and biochemical assays. Results: LGR4 expression was up-regulated in HCC samples, and its expression level was positively correlated with tumor size, microvascular invasion (MVI), TNM stage and pathological differentiation grade of HCC patients. In the mouse HCC model induced by DEN+CCl4, knockdown of LGR4 effectively inhibited the progression of HCC. Silencing of LGR4 inhibited the proliferation, migration, invasion, stem cell-like properties and Warburg effect of HCC cells. These phenotypes were promoted by R-spondin2 (Rspo2), an endogenous ligand for LGR4. Rspo2 markedly increased the nuclear translocation of β-catenin, whereas IWR-1, an inhibitor of Wnt/β-catenin signaling, reversed its effect. Deficiency of LGR4 significantly reduced the nuclear translocation of β-catenin and the expression of its downstream target genes cyclinD1 and c-Myc. Conclusions: LGR4 promotes HCC progression via Wnt/β-catenin signaling pathway. (AU)

Antecedentes: El receptor de acoplamiento de proteínas G de secuencia repetida 4 (LGR4), rico en leucina, juega un papel importante en la diferenciación de células madre, el desarrollo de órganos y el cáncer. Se desconoce si LGR4 afecta la progresión del carcinoma hepatocelular (HCC). El objetivo de este estudio es revelar el papel de LGR4 en el HCC. Métodos: Se recolectaron muestras clínicas de HCC para evaluar la expresión de LGR4 y su correlación con los resultados clínicos de HCC. Alterar los niveles de expresión de LGR4 en las células de HCC mediante métodos farmacológicos y genéticos y analizar el papel de LGR4 en la progresión del cáncer de hígado mediante mediciones in vivo e in vitro. El HCC fue inducido en ratones de tipo salvaje y con defectos de LGR4 con Nitrosamina de dietilo (DEN) y cloruro de carbono (CCl4), y los efectos de LGR4 sobre el HCC fueron detectados por evaluación histopatológica y determinación bioquímica. Resultados: La expresión de LGR4 está regulada en HCC, y su nivel de expresión está positivamente relacionado con el tamaño tumoral, la infiltración microvascular (MVI), la etapa de TNM y el grado de diferenciación patológica en pacientes con HCC. En el modelo de HCC de ratón inducido por DEN+CCl4, golpear bajo LGR4 inhibió efectivamente la progresión del HCC. El silencio de LGR4 inhibe la proliferación, migración, invasión, propiedades similares a las células madre y el efecto Warburg de las células HCC. Estos fenotipos son promovidos por el ligando endógeno roof slab-specific sponge 2 (Rspo2)de LGR4. El Rspo2 aumentó significativamente la translocación nuclear de la proteína beta-catenina, mientras que el inhibidor de la señalización Wnt/beta-cateninaIWR-1 revirtió su acción... (AU)

Stromal osseous metaplasia in urothelial carcinoma of the bladder: An unusual and challenging feature. A case report.

A 62-year-old male presented with pain and haematuria starting 3 months before. The computed tomography showed focal and mural bladder thickening with ureteropelvic dilatation. The following transurethral bladder resection revealed a high-grade muscle-invasive urothelial carcinoma. In the subsequent cystoprostatectomy we found the same tumour, but adding focal tumour-associated stromal osseous metaplasia. Ossifying metaplasia is an extremely rare feature in urothelial carcinoma, with a few reported cases and represents a diagnostic challenge, mimicking radiotherapy-induced sarcoma or sarcomatoid carcinoma.

Rspo2-LGR4 exacerbates hepatocellular carcinoma progression via activation of Wnt/ß-catenin signaling pathway.

BACKGROUND: The leucine-rich repeat-containing G-protein-coupled receptor 4 (LGR4) plays an important role in stem cell differentiation, organ development and cancer. Whether LGR4 affects the progression of hepatocellular carcinoma (HCC) remains unknown. This study aimed to reveal the role of LGR4 in HCC. METHODS: Clinical samples of HCC were collected to assess the expression of LGR4 and its correlation with patients' clinical characteristics. The expression level of LGR4 in HCC cells was altered by pharmacological and genetic methods, and the role of LGR4 in HCC progression was analyzed by in vivo and in vitro assays. HCC was induced by diethylnitrosamine (DEN) and carbon tetrachloride (CCl4) in wild-type and LGR4 deficient mice, the effect of LGR4 on HCC was examined by histopathological evaluation and biochemical assays. RESULTS: LGR4 expression was up-regulated in HCC samples, and its expression level was positively correlated with tumor size, microvascular invasion (MVI), TNM stage and pathological differentiation grade of HCC patients. In the mouse HCC model induced by DEN+CCl4, knockdown of LGR4 effectively inhibited the progression of HCC. Silencing of LGR4 inhibited the proliferation, migration, invasion, stem cell-like properties and Warburg effect of HCC cells. These phenotypes were promoted by R-spondin2 (Rspo2), an endogenous ligand for LGR4. Rspo2 markedly increased the nuclear translocation of ß-catenin, whereas IWR-1, an inhibitor of Wnt/ß-catenin signaling, reversed its effect. Deficiency of LGR4 significantly reduced the nuclear translocation of ß-catenin and the expression of its downstream target genes cyclinD1 and c-Myc. CONCLUSIONS: LGR4 promotes HCC progression via Wnt/ß-catenin signaling pathway.

Sclerosing stromal tumor of the ovary: Two case reports and literature review / Tumor estromal esclerosante de ovario: reporte de 2 casos clínicos y revisión de la literatura

Introduction: Sclerosing stromal tumors (SSTs) are rare benign ovarian tumors. They represent 6% of sex cord stromal tumors. Its preoperative diagnosis is often a challenge due to its similarity to malignant tumors on ultrasound imaging. We present two cases of SSTs to emphasize the consideration of this type of tumors in the differential diagnosis of solid adnexal masses in young women. A review of the literature on the typical ultrasound features, clinical presentation, and management of SSTs was performed. Main symptoms and/or clinical findings: Pelvic pain was the main symptom in both cases. In the first case, transvaginal ultrasound revealed an unilocular solid adnexal mass of 59mm×44mm×45mm with cystic areas and marked peripheral and central vascularization. MRI (magnetic resonance imaging) revealed a 50mm×50mm heterogeneous adnexal mass with a solid peripheral component and a cystic-necrotic center. In the second case, pelvic ultrasound showed a solid cystic adnexal mass of 103mm×77mm with marked peripheral vascularity. Main diagnoses: Postoperative anatomopathological diagnosis in both cases was an ovarian SST.Therapeutic interventions and results. Unilateral laparoscopic salpingo-oophorectomy and oophorectomy, respectively, was performed without incidents. There has been no recurrence during follow-up.Conclusion: It is important to consider SSTs in the differential diagnosis of young women with a unilateral solid-cystic adnexal mass with a high degree of peripheral and central vascularization. Laparoscopic approach together with fertility-sparing techniques should be considered the treatment of choice.(AU)

Introducción: Los tumores esclerosantes del estroma (SST) son tumores benignos raros del ovario. Representan un 6% de los tumores del estroma de los cordones sexuales. Su diagnóstico preoperatorio suele ser un desafío por su similitud ecográfica con los tumores malignos. Presentamos 2 casos de SST para enfatizar la consideración de este tipo de tumores en el diagnóstico diferencial de masas anexiales sólidas en mujeres jóvenes. Se realizó una revisión de la literatura sobre las características ecográficas típicas, la presentación clínica y el manejo de los SST. Principales síntomas y/o hallazgos clínicos: El dolor pélvico fue el síntoma principal en ambos casos. En el primer caso, la ecografía transvaginal reveló una masa anexial unilocular sólida de 59×44×45mm con áreas quísticas y marcada vascularización periférica y central. La resonancia magnética nuclear reveló una masa anexial heterogénea de 50×50mm con componente sólido periférico y un centro quístico-necrótico. En el segundo caso, la ecografía pélvica mostró una masa anexial sólido quística de 103×77mm con marcada vascularización periférica. Diagnósticos principales: El diagnóstico anatomopatológico postoperatorio en ambos casos fue de un SST de ovario.Intervenciones terapéuticas y resultados: Se realizó ooforectomía y salpingooforectomía unilateral laparoscópica, respectivamente, sin incidencias. No se ha producido recidiva durante el seguimiento. Conclusión: Es importante considerar los SST en el diagnóstico diferencial ante mujeres jóvenes con una masa anexial sólido-quística unilateral con un alto grado de vascularización periférica y central. El abordaje laparoscópico junto con técnicas preservadoras de fertilidad deben ser consideradas el tratamiento de elección.(AU)

Upregulation of miR-200a improves ureteral obstruction-induced renal fibrosis via GAB1/Wnt/ß-catenin signaling.

BACKGROUND: Renal fibrosis is a basic pathological change of almost all chronic kidney disorders. Epithelial-mesenchymal transition (EMT) and excessive extracellular matrix (ECM) accumulation play a crucial role in the process of fibrosis. METHODS: Western blot and qRT-PCR were accomplished to analyze the expression levels of target proteins and genes, respectively. The fibrotic levels in the renal tissues of rats were confirmed utilizing Masson staining. Expression of ECM-related α-SMA in the renal tissues was determined by immunohistochemistry assay. The combination of GRB2 associated binding protein 1 (GAB1) and miR-200a was ensured by starBase database and luciferase reporter assay. RESULTS: Our data uncovered that miR-200a was downregulated, but GAB1 was upregulated in the renal tissues of the rat experienced unilateral ureteral obstruction (UUO). Overexpression of miR-200a improved tissues fibrosis, suppressed GAB1 expression and ECM deposition, and inactivated Wnt/ß-catenin in UUO rats. Moreover, miR-200a expression was inhibited, while GAB1 expression was facilitated in the TGF-ß1-induced HK-2 cells. In TGF-ß1-induced HK-2 cells, miR-200a overexpression inhibited GAB1 expression, also declined ECM-related proteins and mesenchymal markers expression. Oppositely, miR-200a overexpression facilitated epithelial marker expression in the TGF-ß1-induced HK-2 cells. Next, the data revealed that miR-200a inhibited GAB1 expression through binding to the mRNA 3'-UTR of GAB1. Increasing of GAB1 reversed the regulation of miR-200a to GAB1 expression, Wnt/ß-catenin signaling activation, EMT and ECM accumulation. CONCLUSION: Overall, miR-200a increasing improved renal fibrosis through attenuating EMT and ECM accumulation by limiting Wnt/ß-catenin signaling via sponging GAB1, indicating miR-200a may be a promising objective for renal disease therapy.

Succinate dehydrogenase inhibitors fungicides: a review of their impact on human health and epigenetic changes / Fungicidas inibidores da succinato desidrogenase: uma revisao de seu impacto na saúde humana e alterares epigenéticas / Fungicidas inhibidores de la succinato deshidrogenasa: una revisión de su impacto en la salud humana y los cambios epigenéticos

Abstract Succinate dehydrogenase inhibitors (SDHIs), fungicides currently most used in agriculture in Brazil, act by blocking the enzyme succinate dehydrogenase (SDH) from plant pathogens. However, studies show that SDHIs can not only inhibit SDH activity in target fungi, but also block that activity in human cells. Considering the medical and agricultural implications of SDH, the purpose of this narrative review is to describe the relationship between exposure to fungicides SDHIs and epigenetic regulation of SDH associated with the development of gastrointestinal stromal tumor, pheochromocytoma/paraganglioma, and cancer. The results obtained with the research showed that the human SDH enzyme exhibited sensitivity to some tested SDHIs, which may cause microcephaly and defects in neurological development. Deficiency of SDH activity causes accumulation of succinate which can act as an oncometabolite inhibit-ing iron-dependent dioxygenases and alpha-ketoglutarate, eleven translocation -TET and histone demethylases, inducing epigenetic changes that lead to multiple cancers and other diseases. Therefore, further in vitro and in vivo analyzes should be performed to assess susceptibility to diseases influenced by the toxic effect of SDHIs.

Resumo Os inibidores da succinato desidrogenase (SDHIs), fungicidas atualmente mais utilizados na agricultura no Brasil, atuam bloqueando a enzima succinato desidrogenase (SDH) de fitopatógenos. No entanto, estudos mostram que SDHIs podem nao apenas inibir a atividade de SDH em fungos alvo, mas também bloquear essa atividade em células humanas. Considerando as implicares médicas e agrícolas do SDH, o objetivo desta revisao narrativa é descrever a relaqao entre a exposiqao a fungicidas SDHIs e a regulaqao epigenética do SDH associada ao desenvolvimento de tumor estromal gastrointestinal, feocromocitoma/paraganglioma e cáncer. Os resultados obtidos com a pesquisa mostraram que a enzima SDH humana apresentou sensibilidade a alguns SDHIs testados, que podem causar microcefalia e defeitos no desenvolvimento neurológico. A deficiencia da atividade da SDH causa acumulo de succinato que pode atuar como um oncometabólito inibindo as dioxigenases dependentes de ferro e alfa-cetoglutarato, onze translocaqóes -TET e histonas desmetilases, induzindo alteraqóes epigenéticas que levam a múltiplos canceres e outras doenqas. Portanto, análises adicionais in vitro e in vivo devem ser realizadas para avaliar a suscetibilidade a doenqas influenciadas pelo efeito tóxico dos SDHIs.

Resumen Los inhibidores de la succinato deshidrogenasa (SDHI), los fungicidas actualmente más utilizados en la agricultura en Brasil, actúan bloqueando la enzima succinato deshidrogenasa (SDH) de los patógenos de las plantas. Sin embargo, los estudios muestran que los SDHI no solo pueden inhibir la actividad de SDH en los hongos objetivo, sino que también bloquean esa actividad en las células humanas. Teniendo en cuenta las implicaciones médicas y agrícolas de SDH, el propósito de esta revisión narrativa es describir la relación entre la exposición a fungicidas SDHI y la regulación epigenética de SDH asociada con el desarrollo de tumores del estro-ma gastrointestinal, feocromocitoma/paraganglioma y cáncer. Los resultados obtenidos con la investigación mostraron que la enzima SDH humana mostró sensibilidad a algunos SDHI probados, lo que puede causar microcefalia y defectos en el desarrollo neurológico. La deficiencia de la actividad de SDH provoca la acumulación de succinato que puede actuar como un oncometabolito que inhibe las dioxigenasas dependientes de hierro y el alfa-cetoglutarato, once translocaciones -TET e histona desmetilasas, induciendo cambios epigenéticos que conducen a múltiples cánceres y otras enfermedades. Por lo tanto, se deben realizar más análisis in vitro e in vivo para evaluar la susceptibilidad a enfermedades influenciadas por el efecto tóxico de los SDHI.

Hallazgo Incidental de Tumor Estromal Gastrointestinal en Divertículo de Meckel. Caso Clínico

Introducción: El divertículo de Meckel es un defecto sacular ubicado en el íleon distal, con una tasa de complicaciones de 4%. La resección quirúrgica está indicada en estas complicaciones, siendo controversial en casos asintomáticos o incidentales. Dentro de las complicaciones existen tumores como los estromales gastrointestinales (GIST). Caso Clínico: Hombre de 57 años, postrado por múltiples factores, presenta úlcera por presión sacra grado IV sobreinfectada y con evolución tórpida. Se decide realizar colostomía terminal, evidenciando un divertículo de Meckel en el intraoperatorio con aspecto sospechoso, por lo cual se decide resecar, resultando en un GIST de bajo riesgo. Se mantiene en seguimiento por 6 meses, sin recidiva tumoral. Discusión: Mientras que la cirugía pareciera ser imperativa en complicaciones, aún existe debate respecto a las indicaciones de resección de divertículo de Meckel hallado incidentalmente en el intraoperatorio por cirugía de otra causa. Si bien puede aumentar la morbimortalidad, la resección estaría indicada según ciertas características como edad, sexo, tamaño y aspecto, dado el riesgo de desarrollo de complicaciones y neoplasias.

Introduction: Meckel's diverticulum is a saccular defect located in the distal ileum, with a complication rate of 4%. Surgical resection is indicated when these complications occur, yet resection in asymptomatic or incidental cases remains controversial. Among these complications, the appearance of tumors such as gastrointestinal stromal (GIST), may occur. Case Report: A 57-year-old male, bedridden due to multi- ple factors, presents with a complicated grade IV sacral pressure ulcer with a torpid evolution. An end colostomy is performed, evidencing a suspicious-looking Meckel's diverticulum intraoperatively, which was resected and resulted to be a low-risk GIST. At a 6-month follow-up, the patient showed no evidence of tumor recurrence. Discussion: While surgery seems to be imperative in complications, there is still a debate regarding the indications for resection of Meckel's diverticulum found incidentally intraoperatively due to surgery for another cause. Although it could increase morbidity and mortality, resection could be indicated according to certain characteristics such as age, sex, size and appearance, given the risk of developing complications and neoplasm.

Sarcoma del estroma endometrial de bajo grado

El sarcoma del estroma endometrial es una neoplasia maligna poco frecuente que se origina en el estroma endometrial. Puede tener varias formas de diferenciación, entre ellas del músculo liso y del cordón sexual. El sarcoma del estroma endometrial de bajo grado es un tipo de tumor endometrial raro, que constituye solo el 0,2% de todas las neoplasias uterinas. Su etiología es desconocida, pero algunos casos se asocian con obesidad, síndrome de ovario poliquístico, diabetes mellitus, menarquia temprana y terapia de sustitución de estrógenos o al tamoxifeno. La sintomatología es inespecífica, varía desde el dolor pélvico hasta el sangrado genital anormal progresivo y es difícil de reconocer por las imágenes radiológicas. En la mayoría de los casos, el diagnóstico se realiza mediante una evaluación anatomopatológica. La tinción inmunohistoquímica también puede ayudar a diferenciarlo de otras neoplasias. Por lo tanto, es importante tener un alto índice de sospecha para este tipo de neoplasia rara. Su tratamiento es quirúrgico y su seguimiento debe ser a largo plazo, debido al alto riesgo de recidivas tardías y metástasis. Se presenta un caso de sarcoma estromal endometrial de bajo grado.

Endometrial stromal sarcoma is a rare malignant neoplasm that originates in the endometrial stroma. It can have several forms of differentiation, including smooth muscle and sex cord. Low-grade endometrial stromal sarcoma is a rare type of endometrial tumor, constituting only 0.2% of all uterine neoplasms. Its etiology is unknown, but some cases are associated with obesity, polycystic ovary syndrome, diabetes mellitus, early menarche, and estrogen replacement therapy or tamoxifen. Symptomatology is nonspecific, ranging from pelvic pain to progressive abnormal genital bleeding, and is difficult to recognize by radiological imaging. In most cases, the diagnosis is made by pathological evaluation. Immunohistochemical staining can also help differentiate it from other neoplasms. Therefore, it is important to have a high index of suspicion for this type of rare neoplasm. Its treatment is surgical and its follow-up should be long term, due to the high risk of late recurrences and metastasis. A case of low-grade endometrial stromal sarcoma is presented.

Granuloma ulcerativo traumático con eosinoflia estromal: lesión simuladora de difícil diagnóstico. Presentación de caso / Traumatic ulcerative granuloma with stromal eosinophilia: Simulator lesión of difcult diagnosis. Presentation of a case

Introducción: el granuloma ulcerativo traumático con eosinofilia estromal es una afección benigna, crónica y autolimitante, que por su evolución clínica puede estar sujeta a confusión diagnóstica. Por ello, el caso que aquí se comparte expone particularidades de esta afección y su respuesta al tratamiento para permitir un mejor conocimiento de esta lesión. Se describen las características clínicas e histopatológicas y su evolución ante la terapéutica empleada. Se presenta una paciente femenina de seis años, con antecedentes de salud y de dientes neonatales, que hace tres meses manifiesta dos úlceras en mucosa sublingual que no cicatrizan ni mejoran al tratamiento anterior. Se indicaron estudios hematológicos, se realizó biopsia incisional de la lesión con su estudio histopatológico e inmunohistoquímico. Se obtuvo eosinofilia estromal y ausencia de linfocitos anómalos CD30. El tratamiento incluyó aplicación de corticosteroides tópicos e intralesionales, experimentando remisión de la lesión. Se mantiene la paciente bajo seguimiento clínico, sin recidiva de lesión. Conclusiones: el granuloma ulcerativo traumático con eosinofilia estromal es una lesión autolimitante que puede ser confundida con otras lesiones ulcerativas de la cavidad bucal, por lo que su estudio histopatológico resulta imprescindible para su diagnóstico. Asimismo, su análisis inmunohistoquímico es indispensable para precisar su naturaleza y probable evolución. El adecuado y exhaustivo proceso diagnóstico constituye una herramienta vital para lograr su identificación.

Background: Traumatic ulcerative granuloma with stromal eosinophilia is a benign, chronicle and self-healing lesion, which can be misdiagnosed for its clinical evolution, for this reason, this case report is carried out, showing particularities of this disease and its response in front to the treatment, giving a better identifcation of the lesion, were described the clinical and histopathological fndings of a case. A feminine patient, six years old, with neonatal health and dental history. She has presented during three months two ulcerative lesions in sublingual mucosa, which do not improve with the previous treatment. Hematological studies and biopsy were carried out, the incisional biopsy was analyzed with immunohistochemical test, the results were stromal eosinophilia and absence of anomalous lymphocytes CD30. She was treated with topical and intralesional corticosteroids, experiencing remission of the lesion. The patient had a long clinical follow up without recidive. Traumatic ulcerative granuloma with stromal eosinophilia is a self-healed lesion that needs a histopathological and inmunohistochemical analysis for an adequate diagnosis. The correct diagnostic sequence is a vital tool to achieve its identification.

Condroma pulmonar y paraganglioma carotídeo como manifestaciones de la tríada de Carney: reporte de un caso / Pulmonary chondroma and carotid paraganglioma as expressions of Carney's triad: report of a case

Resumen Objetivos: Presentar caso clínico y revisión de la literatura sobre asociación de tumores poco frecuentes compatibles con diagnóstico de tríada de Carney. Paciente y Métodos: Revisión de ficha clínica de paciente de sexo femenino de 39 años de edad con antecedentes de asma, quien acude a servicio de urgencias por síntomas respiratorios. En estudio con imágenes se evidencia masa pulmonar en lóbulo superior derecho probablemente hamartoma y masa en la bifurcación carotídea izquierda compatible con posible paraganglioma. Se completó el estudio con endoscopia digestiva alta sin evidencia de tumor gástrico y PET-CT (tomografía de emisión de positrones-tomografía computarizada) que descartó otras lesiones. Resultados: La paciente fue sometida a resección quirúrgica de ambos tumores (pulmonar y carotídeo). En estudio histopatológico diferido, se plantean los diagnósticos de paraganglioma carotideo y hamartoma pulmonar, el cual, luego de una segunda revisión histopatológica, es corregido a condroma pulmonar. Discusión: La tríada de Carney se compone por la asociación de al menos 2 de 3 tumores: tumor estromal gastrointestinal (GIST), paraganglioma extra-adrenal y condroma pulmonar. Su expresión es variable, coexistiendo en forma completa en solo el 22% de los casos. Conclusión: Los pacientes con sospecha de tríada de Carney deben recibir evaluación multidisciplinaria, estudio completo en búsqueda de tumores asociados y seguimiento a largo plazo por posibles recurrencias o metástasis.

Objective: To present a clinical case and review of the literature on the infrequent association of pulmonary and extra thoracic tumors compatible with Carney's triad. Patient and Methods: Review of clinical records of a 39 years-old female patient with history of asthma who presented in the emergency department with respiratory symptoms. An imaging study showed a pulmonary mass in the right upper lobe with the aspect of hamartoma and a mass in the left carotid artery bifurcation compatible with a possible paraganglioma. Upper gastrointestinal endoscopy showed no evidence of gastric tumor and a PET-CT (Positron Emission Tomography - Computed Tomography) excluded other lesions. Results: Patient underwent surgical resection of both tumors (pulmonary and carotid). Diagnosis of carotid paraganglioma and pulmonary hamartoma were stated by histopathology. However, lung tumor after a second pathological analysis was confirmed to be a pulmonary chondroma. Discussion: Carney's triad is defined by the association of at least 2 of 3 tumors: Gastrointestinal Stromal Tumor (GIST), extraadrenal paraganglioma and pulmonary chondroma. Its expression is variable, coexisting completely in only 22% of cases. Conclusion: Patients with suspected Carney's triad should receive a multidisciplinary assessment, a complete study searching associated tumors and long-term follow-up for recurrences or metastases.

Evidence in the prevention of the recurrence of herpes simplex and herpes zoster keratitis after eye surgery.

OBJECTIVE: Herpetic keratitis, either due to herpes simplex keratitis (HSK) or herpes zoster ophthalmicus (HZO), can recur after eye surgery.º Prophylaxis is postulated as necessary to avoid it. The objective of this study was to review the scientific evidence on the preventive methods used in the perioperative period in patients previously affected by HSK/HZO. METHODS: An exhaustive search was carried out in the PubMed and Web of Science databases to identify relevant articles on prophylaxis and risk of recurrence of HSK/HZO in patients undergoing eye surgery up to 31 December 2019. RESULTS: There is strong evidence that oral prophylaxis should be recommended after penetrating keratoplasty in patients who have previously had HSK/HZO. For other types of surgery, the evidence is less compelling. However, a latent period of inactivity should be considered between disease and oral prophylaxis. CONCLUSIONS: Penetrating and lamellar keratoplasty, corneal crosslinking, cataract surgery, and photorefractive and phototherapeutic surgery cause an alteration of the subbasal nerve plexus of the cornea. Due to surgical trauma, as well as the modulation of the ocular immune response caused by steroids applied in the postoperative period, it is possible to induce the reactivation of HSK/HZO, which is common in some cases. Within this article, we discuss the available evidence for HSK/HZO prophylaxis in eye surgery. Further studies are necessary to define the real risk of HSK/HZO recurrence after ocular surgeries, particularly in cataract surgery, and to confirm the efficacy of perioperative prophylaxis with anti-HSK/HZO antivirals.

Hiperplasia estromal pseudoangiomatosa (HEP) de mama: a propósito de un caso / Pseudoangiomatous stromal hyperplasia (PASH) of the breast: about a case

La hiperplasia pseudoangiomatosa estromal de la mama es una patología benigna de rara aparición en mujeres, que hoy en día sigue generando incertidumbre en cuanto a su manifestación y al tratamiento definitivo. Nuestro objetivo será detallar el manejo y los resultados obtenidos luego de tratar a una paciente con esta patología atendida en hospital público durante la pandemia, que presentó gigantomastia bilateral a expensas de crecimiento y simetrización de mama contralateral afectada por HEP durante su estado gravídico.

Pseudoangimatous stromal hyperplasia of the breast, is a pathology of rare appearance, in women, which today continues to generate uncertainty regarding its manifestation and definitive treatment. Our objective will be to detail the management and results obtained after treating a patient with this pathology in a public hospital during a pandemic. who presented bilateral gigantomastia at the expense of growth and symmetrization of the contralateral breast affected by HEP during her pregnancy.

Evidencia en la prevención de la recurrencia de queratitis por herpes simple y herpes zóster tras cirugía ocular / Evidence in the prevention of the recurrence of herpes simplex and herpes zoster keratitis after eye surgery

Propósito: La queratitis herpética, ya sea por herpes simple (HSK) o por herpes zóster oftálmico (HZO) puede presentar recaídas tras la cirugía ocular. Se postula como necesaria una profilaxis para evitarla. El objetivo de este estudio es revisar la evidencia científica sobre los métodos preventivos empleados en el período perioperatorio en pacientes previamente afectados de HSK/HZO.MétodosSe ha realizado una búsqueda exhaustiva en las bases de datos PubMed y Web of Science para identificar artículos relevantes sobre profilaxis y riesgo de recurrencia de HSK/HZO en pacientes sometidos a cirugía ocular hasta el 31 de diciembre de 2019.ResultadosHay pruebas sólidas de que la profilaxis oral debe recomendarse tras una queratoplastia penetrante en pacientes que hayan sufrido previamente HSK/HZO. Para otros tipos de cirugías, la evidencia es menos convincente; sin embargo, debe considerarse un período latente de inactividad entre la enfermedad y la profilaxis oral.ConclusionesLa queratoplastia penetrante y lamelar, crosslinking corneal, cirugía de catarata y cirugía fotorrefractiva y fototerapéutica provocan una alteración del plexo nervioso sub-basal de la cornea. Debido al traumatismo quirúrgico, así como a la modulación de la respuesta inmunológica ocular causada por los esteroides aplicados en el postoperatorio, es posible inducir la reactivación de HSK/HZO, siendo en algunos casos común. Dentro del presente artículo discutimos la evidencia disponible para la profilaxis de HSK/HZO en cirugía ocular. Son necesarios estudios adicionales para definir el riesgo real de recurrencia de HSK/HZO después de cirugías oculares, particularmente en cirugía de catarata y para confirmar la eficacia de la profilaxis perioperatoria con antivíricos anti HSK/HZO (AU)

Objective: Herpetic keratitis, either due to herpes simplex keratitis (HSK) or herpes zoster ophthalmicus (HZO), can recur after eye surgery.° Prophylaxis is postulated as necessary to avoid it. The objective of this study was to review the scientific evidence on the preventive methods used in the perioperative period in patients previously affected by HSK/HZO.MethodsAn exhaustive search was carried out in the PubMed and Web of Science databases to identify relevant articles on prophylaxis and risk of recurrence of HSK/HZO in patients undergoing eye surgery up to 31 December 2019.ResultsThere is strong evidence that oral prophylaxis should be recommended after penetrating keratoplasty in patients who have previously had HSK/HZO. For other types of surgery, the evidence is less compelling. However, a latent period of inactivity should be considered between disease and oral prophylaxis.ConclusionsPenetrating and lamellar keratoplasty, corneal crosslinking, cataract surgery, and photorefractive and phototherapeutic surgery cause an alteration of the subbasal nerve plexus of the cornea. Due to surgical trauma, as well as the modulation of the ocular immune response caused by steroids applied in the postoperative period, it is possible to induce the reactivation of HSK/HZO, which is common in some cases. Within this article, we discuss the available evidence for HSK/HZO prophylaxis in eye surgery. Further studies are necessary to define the real risk of HSK/HZO recurrence after ocular surgeries, particularly in cataract surgery, and to confirm the efficacy of perioperative prophylaxis with anti-HSK/HZO antivirals (AU)

Úlcera eosinofílica lingual: a propósito de un caso clínico / Eosinophilic ulcer of the tongue: case report

Introducción: La úlcera eosinofílica es una lesión infrecuente y benigna de la mucosa oral, caracterizada por su rápida instauración y evolución crónica. Su localización, predominantemente lingual; su aspecto con fondo necrótico de bordes indurados, y largo período de cicatrización, hacen que sea imprescindible su diagnóstico diferencial con un cáncer oral de células escamosas. Se atribuye su causa a un agente traumático, siendo este ausente en la mitad de los casos. Histológicamente, presenta un denso infiltrado inflamatorio polimorfo, con eosinófilos de tamaño aumentado. Objetivo: Se presenta un caso clínico de úlcera eosinofílica y una revisión bibliográfica actualizada con el objetivo de analizar sus factores etiológicos y sus opciones terapéuticas. Caso clínico: Paciente, mujer de 75 años, con una úlcera en el borde lingual derecho, de 1 cm de diámetro y 4 meses de evolución acompañada de un dolor intenso. En un período de 3 meses, se biopsió dos veces por su recidiva. En ambas biopsias, el estudio anatomopatólogico confirma la presencia de una intensa displasia epitelial, con un denso infiltrado inflamatorio, sin evidencia de un proceso neoplásico. Posteriormente, se trató con la aplicación tópica en gel de acetónido de triamcinolona al 0,5%, con el que la lesión curó en tres meses. Conclusión: La úlcera eosinofílica posee una etiopatogenia indeterminada. El agente traumático, se establece como factor predisponente. La biopsia es la medida principal para el diagnóstico y tratamiento de la lesión. Aunque no queda demostrada la eficacia de la aplicación de corticoides tópicos, suponen una mejoría en la evolución y sintomatología de la lesión. (AU)

Introduction: The eosinophilic ulcer is a rare benign lesion of the oral mucosa. It is known for its rapid onset and chronic course. Due to its main location, the tongue, clinical features and its slowhealing process, a differential diagnosis with oral squamous cell carcinoma is necessary. It is suggested that it is caused by local trauma, yet it is missing in half of the cases. The histopathological findings include dense polymorphic inflammatory infiltrate, with large eosinophils. Objective: We aim to report a case of eosinophilic ulcer and an updated literature review to analyse its etiological factors and treatment options. Case report: We present a case of a 75-year-old woman, with a painful ulcer in the right border of the tongue, which appeared 4 months ago. It had a diameter of 1 cm. In a period of 3 months, it had been biopsied twice, due to its recurrence. Both histological findings confirm the presence of a dense polymorphic inflammatory infiltrate, epithelial dysplasia and no neoplastic evidence. Afterwards, the lesion was treated with topical application of triamcinolone acetonide 0.5% and it healed within 3 months. Conclusion: Eosinophilic ulcer has an undetermined etiopathogenesis. Trauma is considered as a contributing factor. Biopsy is the best approach for diagnosis and treatment. Although with no clear evidence, the application of topical corticosteroids improves lesion development and symptoms. (AU)

Alcance de las células madre derivadas de tejido adiposo / Scope of stem cells derived from adipose tissue

Introducción: En el tejido adiposo se han identificado células madre mesenquimales con capacidad autorrenovadora y multipotencial. Mediante digestión enzimática y centrifugado del lipoaspirado se libera una población heterogénea de células denominada fracción vascular estromal, con innumerables potencialidades terapéuticas en el campo de la medicina regenerativa. Objetivo: Actualizar el alcance de las células madre derivadas de tejido adiposo en la terapia regenerativa. Método: Se revisaron 38 artículos entre los años 2000 y 2019 en las bases de datos Scielo, ScienceDirect, Medline y Pubmed. Desarrollo: Las células de la fracción vascular estromal se caracterizan por su capacidad de generar tejido adiposo y vasos sanguíneos, y por la producción de factores de crecimiento que ayudan en la supervivencia de los adipocitos y la formación de una red vascular. El principal mecanismo de acción de las células madre derivadas de tejido adiposo parece deberse a su acción paracrina y a la sinergia con células endoteliales. En el campo de la medicina regenerativa se han utilizado en el tratamiento de cicatrices patológicas y de fibrosis deformantes con impotencia funcional, en las reconstrucciones de secuelas por cáncer y en el cierre precoz de zonas cruentas. Conclusiones: La lipotransferencia es un procedimiento con un mínimo de complicaciones que constituye una de las opciones terapéuticas más empleadas para corregir defectos en los tejidos, debido a que no solo es un medio de relleno, sino que también permite la regeneración y restauración tisular. La presencia de células madre en el tejido adiposo, unido a su accesibilidad, disponibilidad e histocompatibilidad, ha motivado su aplicación cada vez más expandida en la medicina estética, reconstructiva y regenerativa(AU)

Introduction: Mesenchymal stem cells with self-renewing and multipotential capacity have been identified in adipose tissue. By means of enzymatic digestion and centrifugation of the lipoaspirate a heterogeneous population of cells called vascular stromal fraction is released. It has innumerable therapeutic potentialities in the field of regenerative medicine. Objective: To update the scope of stem cells derived from adipose tissue in regenerative therapy. Method: 38 articles published between 2000 and 2019 in the Scielo, ScienceDirect, Medline and Pubmed databases were reviewed. Development: The cells of the vascular stromal fraction are characterized by generating adipose tissue and blood vessels and by the production of growth factors that help in the survival of adipocytes and the formation of a vascular network. The main mechanism of action of stem cells derived from adipose tissue appears to be due to their paracrine action and synergy with endothelial cells. Stem cells derived from adipose tissue have been used in regenerative medicine for the treatment of pathological scars and deforming fibrosis with functional impotence, in the reconstruction of cancer sequelae and in the early closure of bloody areas. Conclusions: Lipotransfer is a procedure with a minimum of complications that constitutes one of the most widely used therapeutic options to correct tissue defects, since it is not only a filling medium, but also allows tissue regeneration and restoration. The presence of stem cells in adipose tissue, together with their accessibility, availability and histocompatibility, has motivated their increasingly widespread application in aesthetic, reconstructive and regenerative medicine(AU)

Tumores estromales gastrointestinales (GIST) gástricos, serie de casos / Gastrointestinal stromal tumors (GIST). Case series

Resumen Introducción: Los tumores estromales gastrointestinales (GIST) representan hasta el 2 % de las neoplasias gastrointestinales, estos aparecen en cualquier parte del tracto gastrointestinal y son encontrados más frecuentemente en el estómago (60 %). El diagnóstico se realiza por la expresión de un receptor de factor de crecimiento de tirosina-cinasa, antígeno de diferenciación (CD) 117, lo que lo diferencia de los otros tumores mesenquimales como leiomiomas, leiomiosarcomas, leiomioblastomas y tumores neurogénicos, que no expresan esta proteína. Objetivo: El objetivo de nuestro trabajo es caracterizar los GIST de localización gástrica con respecto a su presentación clínica, diagnóstico, manejo, recurrencia y supervivencia. Métodos: Se trata de un estudio observacional, retrospectivo basado en una serie de casos. Se realizó una extracción de la información por medio de la revisión de las historias clínicas de los pacientes con GIST gástricos en un centro oncológico de Bogotá entre enero de 2005 y diciembre de 2015. La información recolectada incluyó tipo de manejo y abordaje quirúrgico, localización, tamaño, índice mitótico y clasificación de riesgo. Resultados: Se encontraron 31 pacientes con diagnóstico de GIST gástrico. La edad media fue de 62,3 años, con una mediana de 61 años. De los 31 pacientes, 18 fueron mujeres y 13 hombres. El tiempo de seguimiento estuvo entre un mínimo de 2,4 meses y un máximo de 214 meses, La mediana de seguimiento fue de 36 meses. Conclusiones: Los GIST son tumores potencialmente malignos, y el de localización gástrica es el más frecuente. El diagnóstico y tratamiento dependen de su tamaño y localización dentro del estómago. El manejo es variado y consiste en la resección quirúrgica, en la que los procedimientos son mínimamente invasivos, en combinación con la endoscopia, que son una buena alternativa al tratamiento abierto hasta que haya necesidad de terapia sistémica.

Abstract Introduction: Gastrointestinal stromal tumors (GIST) account for up to 2% of gastrointestinal neoplasms. They may appear anywhere in the gastrointestinal tract and are most frequently found in the stomach (60%). The diagnosis is made based on the expression of the tyrosine-protein kinase KIT CD117, which differentiates it from other mesenchymal tumors such as leiomyomas, leiomyosarcomas, leiomyoblastomas, and neurogenic tumors, that do not express this protein. Objective: To characterize the clinical presentation, diagnosis, treatment, recurrence, and survival of GISTs in the stomach. Materials and methods: This is an observational retrospective study based on a case series. Data was collected after reviewing the medical records of patients diagnosed with GIST at a cancer center in Bogotá between January 2005 and December 2015. The data included type of treatment and surgical approach, location, size, mitotic index, and risk classification. Results: There were 31 patients diagnosed with GIST. Their mean age was 62.3 years, with a median of 61 years. Of the 31 patients, 18 were women and 13 were men. Follow-up time ranged from a minimum of 2.4 months to a maximum of 214 months. The median follow-up time was 36 months. Conclusions: GISTs are potentially malignant tumors, with gastric location being the most frequent. Diagnosis and treatment depend on their size and location in the stomach. Treatment options vary, ranging from surgical resection, where minimally invasive procedures along with endoscopy are a suitable alternative to open surgery, to the need for systemic therapy.

Abnormal thymic stromal lymphopoietin expression in the gastrointestinal mucosa of patients with eosinophilic gastroenteritis / Expressão anormal da linfopoietina estromal tímica na mucosa gastrointestinal depacientes com gastroenterite e osinofílica

Abstract Objective: To investigate the differential expression of the thymic stromal lymphopoietin isoforms, short and long, and discern their biological implications under eosinophilic gastroenteritis. Methods: The expression of thymic stromal lymphopoietin and its two isoforms in tissues was assessed by quantitative RT-PCR in healthy controls (n = 24) and patients with eosinophilic gastroenteritis (n = 17). Results: Thymic stromal lymphopoietin mRNA was significantly reduced in eosinophilic gastroenteritis when compared with healthy controls (p < 0.0001). A significantly lower amount of short thymic stromal lymphopoietin mRNA was observed in eosinophilic gastroenteritis when compared with controls (p < 0.05), while a significantly higher amount of long thymic stromal lymphopoietin mRNA was observed in eosinophilic gastroenteritis when compared with controls (p < 0.05). Peak eosinophilic count is significantly positively correlated with the expression of long thymic stromal lymphopoietin mRNA in the gastrointestinal mucosal of patients with eosinophilic gastroenteritis (r s = 0.623, p < 0.005), while peak eosinophilic count is significantly negatively correlated with the expression of short thymic stromal lymphopoietin mRNA in the gastrointestinal mucosal of patients with eosinophilic gastroenteritis (r s = −0.4474, p < 0.05). Conclusions: Abnormal mucosal thymic stromal lymphopoietin expression may contribute to gastrointestinal mucosa damage in eosinophilic gastroenteritis.

Resumo Objetivo: Investigar a expressão diferencial das isoformas da linfopoietina estromal tímica, curta e longa, e discernir suas implicações biológicas na gastroenterite eosinofílica. Métodos: Avaliamos a expressão das isoformas da linfopoietina estromal tímica e suas duas isoformas através da técnica RT-PCR quantitativa em tecidos de controles saudáveis (n = 24) e pacientes com gastroenterite eosinofílica (n = 17). Resultados: Demonstramos que o RNAm das isoformas da linfopoietina estromal tímica estava significativamente reduzido na gastroenterite eosinofílica em comparação com os controles saudáveis (p < 0,0001). Também descobrimos uma quantidade significativamente menor de RNAm das isoformas da linfopoietina estromal tímica curta na gastroenterite eosinofílica em comparação com os controles (p < 0,05) e uma quantidade significativamente maior de RNAm das isoformas da linfopoietina estromal tímica longa na gastroenterite eosinofílica em comparação com os controles (p < 0,05). O pico da contagem eosinofílica está correlacionado positiva e significativamente com a expressão do RNAm das isoformas da linfopoietina estromal tímica longa na mucosa gastrointestinal de pacientes com gastroenterite eosinofílica (rs = 0,623, p < 0,005), enquanto o pico de contagem eosinofílica está negativa e significativamente correlacionado com a expressão do RNAm das isoformas da linfopoietina estromal tímica curta na mucosa gastrointestinal de pacientes com gastroenterite eosinofílica (rs = -0,4474, p < 0,05). Conclusões: A expressão anormal das isoformas da linfopoietina estromal tímica na mucosa pode contribuir para o dano da mucosa gastrointestinal na gastroenterite eosinofílica.

A rectal gastrointestinal stromal tumor - a plea for neoadjuvant imatinib and TAMIS / Tumor estromal gastrointestinal no reto - um caso de uso de imatinibe neoadjuvante e TAMIS

Abstract Here we describe an infrequent case of gastrointestinal stromal tumor of the rectum in a 57 year-old man with spindle cell neoplasm probably gastrointestinal stromal tumor and CT scan showed tumor from the anterior rectal wall and offered abdominoperineal resection for the same. The patient was started on imatinib and had a significant reduction in symptoms. The patient was reassessed with the CT scan, which showed a reduction in tumor size and Transanal minimally invasive surgery was planned for the patient. Use of imatinib prior to surgical resection to attain the reduced size of the tumor within the limit of resection is an attractive approach. Since tumor development can happen rapidly again after substantial tumor shrinkage, the best time to operate depending on resectability and the maximum therapeutic outcome remains divisive.

Resumo No presente estudo, os autores descrevem um caso raro de tumor estromal gastrointestinal no reto em um homem de 57 anos que se apresentou com neoplasia de células fusiformes, com provável tumor estromal gastrointestinal. A tomografia computadorizada demonstrou tumor na parede anterior do reto e foi sugerida sua ressecção abdominoperineal. O paciente iniciou tratamento com imatinibe e apresentou uma redução significativa nos sintomas. O paciente foi reavaliado por tomografia computadorizada, que evidenciou redução do tamanho do tumor; portanto, foi indicada cirurgia transanal minimamente invasiva. O tumor era ressecável e foi necessário um extenso acompanhamento para romper o órgão, de forma a alcançar a ressecção máxima; caso contrário, o tumor estromal gastrointestinal também seria irressecável. O uso de imatinibe antes da ressecção cirúrgica para reduzir o tamanho do tumor dentro do limite de ressecção é uma abordagem interessante. Como o tumor pode se crescer rapidamente após ser substancialmente reduzido, a literatura ainda apresenta controvérsias quanto ao melhor momento para operar e quanto ao melhor desfecho terapêutico.

Abnormal thymic stromal lymphopoietin expression in the gastrointestinal mucosa of patients with eosinophilic gastroenteritis.

OBJECTIVE: To investigate the differential expression of the thymic stromal lymphopoietin isoforms, short and long, and discern their biological implications under eosinophilic gastroenteritis. METHODS: The expression of thymic stromal lymphopoietin and its two isoforms in tissues was assessed by quantitative RT-PCR in healthy controls (n=24) and patients with eosinophilic gastroenteritis (n=17). RESULTS: Thymic stromal lymphopoietin mRNA was significantly reduced in eosinophilic gastroenteritis when compared with healthy controls (p<0.0001). A significantly lower amount of short thymic stromal lymphopoietin mRNA was observed in eosinophilic gastroenteritis when compared with controls (p<0.05), while a significantly higher amount of long thymic stromal lymphopoietin mRNA was observed in eosinophilic gastroenteritis when compared with controls (p<0.05). Peak eosinophilic count is significantly positively correlated with the expression of long thymic stromal lymphopoietin mRNA in the gastrointestinal mucosal of patients with eosinophilic gastroenteritis (rs=0.623, p<0.005), while peak eosinophilic count is significantly negatively correlated with the expression of short thymic stromal lymphopoietin mRNA in the gastrointestinal mucosal of patients with eosinophilic gastroenteritis (rs=-0.4474, p<0.05). CONCLUSIONS: Abnormal mucosal thymic stromal lymphopoietin expression may contribute to gastrointestinal mucosa damage in eosinophilic gastroenteritis.