A nonobstructive condition: Medial arterial calcification / 中南大学学报(医学版)

Vascular calcification, including intimal and medial calcification, is closely associated with a significant increase in cardiovascular diseases. Although increased understandings were achieved, people still know much more about intimal calcification than medial calcification because the latter doesn't obstruct the arterial lumen, commonly considered as a non-significant finding. We clarified the pathologic characteristic of medial calcification, its difference from intimal calcification, principally focused on its clinical relevance, such as diagnosis, nosogenesis, and hemodynamics. We underline the importance of identifying and distinguishing medial calcification, understanding its effect to local/systematic arterial compliance, and relationship to diabetic neuropathy. Recent studies emphasize do not ignore its predictive role in cardiovascular mortality. It is of great clinical significance to summarize the mechanisms of occurrence, lesion characteristics, diagnostic methods, pathogenic mechanisms, hemodynamic changes, and the distinction as well as association of intimal calcification with intimal calcification.

Effect of HER2 and Fascin expression on muscle-invasive bladder cancers: Classification by basaloid and luminal phenotypes

Purpose: The present study aims to identify basaloid and luminal molecular groups and the p53-like sub-group, which is a sub-group of the luminal group, using a specific immunohistochemical panel and investigate human epithelial growth factor receptor 2 (HER2)/Neu and Fascin expression in these groups to analyze their relationship with clinicopathological features and prognosis in a cohort of cases with muscle-invasive urothelial bladder carcinoma (MIBC). Material and Methods: An immunohistochemical panel that included GATA-3, CK20, CD44, and CK5/6 was used to identify molecular sub-groups based on expression in 44 cases of MIBC. HER2/Neu and Fascin expression in basal, luminal, and p53-like groups and the relationship with clinicopathological features and prognosis were investigated. Results: The distribution of the molecular sub-groups determined by immunohistochemistry was as follows: 23 luminal cases (52.3%), 16 basal cases (36.4%), and 5 (11.4%) p53-like cases. There was a statistically significant difference in tumor size across the groups, with the greatest size in the p53-like group (p = 0.001). A statistically significant difference was observed in HER2/Neu expression between the molecular sub-groups (p = 0.017). Comparison of survival and HER2/Neu scores revealed shorter survival in patients with an HER2/Neu score of 3 + compared to those with scores of 0, 1+, and 2+ (p = 0.109). Fascin immunoreactivity was more common in the p53-like and basal groups compared to the luminal group (p = 0.036). Conclusion: Despite the limited number of cases in the MIBC group, our results support that HER2/Neu expression in the luminal sub-group and Fascin expression in basal and p53-like groups may be used as a negative prognostic marker. Multi-center studies that include large case series are warranted in this field.

Changes of choroidal structure in children with hyperopic amblyopia observed by EDI-OCT technique / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To compare the differences in choroidal structure between hyperopic amblyopia and normal children of the same age by the enhanced depth imaging optical coherence tomography(EDI-OCT)technique.METHODS: There were 35 cases in 50 eyes of children with hyperopic amblyopia visiting our hospital in January 2021 to December 2021 selected in the amblyopic group, and 30 cases in 51 eyes of healthy children who matched general data in the same period were selected in the control group. EDI-OCT examination was performed to measure the choroidal thickness(CT). After image processing, the total choroidal area(TCA), luminal area(LA), stromal area(SA)and choroidal vascularity index(CVI)were obtained.RESULTS: TCA(except inferior quadrant), SA(except inferior quadrant of the outer ring), LA and CT(except inferior and temporal quadrant )in the amblyopic group of each area were significantly larger than that in the control group(P<0.05), and there was no significant difference in CVI between the two groups except the temporal quadrant of the outer ring(P>0.05). There was no significant difference in CT for all degrees of hyperopic amblyopia, with the exception of the nasal quadrant(P>0.05).CONCLUSION: Hyperopic amblyopia is accompanied with abnormal choroidal structure. As the degree of hyperopia increases, TCA, LA and SA exhibit increasing trends. The changes in choroidal structure are presumed to be related to hyperopic amblyopia.

Valor pronóstico de la baja expresión del receptor de estrógeno en pacientes con cáncer de mama LUMINAL HER2 negativo / Prognostic value of low estrogen receptor expression in patients with luminal HER2-negative breast cancer

Introducción: El subtipo luminal de cáncer de mama es sensible a la terapia antiestrógenica y muestra un mejor pronóstico que el del cáncer de mama con receptor del factor de crecimiento epidérmico humano 2 enriquecido (HER2) o triple negativo. Sin embargo, el cáncer de mama tipo luminal es heterogéneo y puede tener características clínicas agresivas. Investigamos las implicaciones clínicas y pronósticas de la baja expresión del receptor de estrógeno en un grupo de carcinomas luminales HER2 negativos. Material y método: Recolectamos los datos de un grupo de 367 cánceres de mama luminales HER2 negativo que eran receptor de estrógeno (RE) positivos y receptor de progesterona (RP) positivos o negativos y los dividimos en RE+ alto (RE) y RE+ bajo (REB). Se definió REB de acuerdo a la úl- tima actualización ASCO /CAP de las recomendaciones del testeo de de RH en cáncer de mama como aquellos con expresión entre 1 y 10%. Analizamos los datos clínico-patológicos y la supervivencia según los grupos de RE y REB. Resultados: Edad media 63,9+12.8 años. Tamaño tumoral: 1,9 +0.9 cm. Se realizó Mastectomía radical modificada en 61% de los pacientes. Tipo histológico más frecuente: Ductal Infiltrante en 89,5% de los casos. Hallazgos que concuerdan con publicaciones de otros centros. Discusión: Los tumores REB resultaron en 1,6%. No hubo diferencias estadísticas en el estadio TNM y tipo histológico. Sin embargo, el grupo REB se asoció con menor edad (47 vs 57 años), tipo luminal B, mayor grado histológico y Ki 67 alto (>30%). Si bien las diferencias en supervivencia global (SG) no fueron significativas (p=0,279), observamos que a partir de los 60 meses de seguimiento la SG fue menor en el grupo REB que en el grupo RE. Conclusiones: La baja expresión del RE se asoció peor pronóstico. Podríamos considerar la baja expresión del RE como marcador pronóstico en el subtipo luminal HER2 negativo de cáncer de mama. Debido a la baja incidencia de casos REB consideramos necesario estudios adicionales con mayor número de pacientes que podrían revelar su papel negativo en el cáncer de mama.

Introduction: The luminal subtype of breast cancer is sensitive to antiestrogenic therapy and shows a better prognosis than human epidermal grow- th factor receptor 2 (HER2) enriched or triple negative breast cancer. However, luminal type breast cancer is heterogeneous and can have aggressive clinical features. We investigated the clinical and prognostic implications of low estrogen receptor expression in a group of HER2-negative luminal carcinomas. Material and method: We collected data from a group of 367 HER2 negative luminal breast cancers that were estrogen receptor (ER) positive and progesterone receptor (PR) positive or negative and divided them into ER + high (ER) and ER + low (ERL). ERL was defined when RE expression was < 10%. We analyzed the clinical-pathological data and survival accor- ding to the ER and ERL groups. Results: ERL tumors resulted in 1.6%. There were no statistical differences in TNM stage and histological type. However, the ERL group was as- sociated with younger age (47 vs 57 years), luminal type B, higher histological grade, and high Ki 67 (> 30% ). Although the differences in overall survival (OS) were not significant (p = 0.279), we observed that after 60 months of follow-up the OS was lower in the ERL group than in the ER group. Conclusions: Low ER expression was associated with a worse prognosis. We could consider low ER expression as a prognostic marker in the HER2-ne- gative luminal subtype of breast cancer. Due to the low incidence of ERL cases, we consider necessary additional studies with a larger number of patients that could reveal its negative role in breast cancer.

EndoFLIP: una nueva tecnología / EndoFLIP: a new technology

Resumen Mediante la distensión de un balón con líquido conductor, la sonda de imagen luminal funcional endoluminal (EndoFLIP) evalúa las propiedades biomecánicas como la distensibilidad, volumen, presión e inclusive diámetros de regiones esfinterianas como la unión gastroesofágica, píloro y ano. La mayor evidencia en la utilidad clínica de la EndoFLIP está en los trastornos de motilidad esofágica, principalmente para identificar acalasia cuando la manometría esofágica de alta resolución y otras imágenes no logran diagnosticarla e inclusive, mediante el programa de FLIP 2.0, caracteriza la acalasia en subtipos a partir de patrones de motilidad del esófago distal en respuesta a la distensión. Se ha demostrado recientemente que la EndoFLIP tiene un rol diagnóstico, pronóstico o terapéutico en otras patologías como la esofagitis eosinofílica, reflujo gastroesofágico, gastroparesia, durante la fundoplicatura y dilatación esofágica.

Abstract EndoFLIP evaluates biomechanical properties such as distensibility, volume, pressure, and even diameters of sphincter regions like the gastroesophageal junction, pylorus, and anus, by distending a balloon with a conductive medium. The best evidence of the clinical utility of EndoFLIP is observed in esophageal motility disorders, mainly when identifying achalasia when high-resolution esophageal manometry and other images fail to diagnose it. Even EndoFLIP 2.0 characterizes achalasia into subtypes based on distal esophageal motility patterns in response to distention. Recently, it has been shown that this system has a diagnostic, prognostic and/or therapeutic role in other diseases such as eosinophilic esophagitis, gastroesophageal reflux, and gastroparesis, and during fundoplication and esophageal dilation.

Potential health benefits of resveratrol: a pharmacokinetics-caused conundrum / 中国临床药理学与治疗学

Resveratrol (3, 5, 4'-trihydroxy-trans-stilbene) was first identified from white hellebore (Veratrum grandiflorum) root and began to attract interest when its presence in red wine and cardiovascular activities were reported, leading to speculation of its contribution to the 'French paradox'. Besides the cardiovascular protection, potential health benefits of resveratrol include calorie restriction-like effects, cancer prevention and adjunctive therapy, and neuroprotection. In order to achieve translational applications of these potential benefits, pharmacokinetic research was performed for plasma pharmacokinetics and related disposition of orally dosed resveratrol. This paper summarizes the known human pharmacokinetic characteristics of resveratrol after oral administration and various attempts to improve its systemic exposure level from the perspectives of systemic exposure and in vivo process. However, available pharmacokinetic data of resveratrol has raised conundrums that limit translating potential benefits to clinics: (1) differences between the unchanged resveratrol used in bioactivity studies and its major circulating forms (i.e., metabolites) after dosing; (2) resveratrol's test concentrations used to exert in vitro bioactivities related to the benefits significantly higher than the compound's clinically achievable concentrations; (3) resveratrol's concentrations achievable (estimated from the pharmacokinetics) from doses used to produce in vivo efficacy significantly lower than the effective concentrations found in studies of related action mechanism (suggesting unreliability of test mechanism). In the last part of this review, we provide recommendations for future pharmacokinetic investigations of resveratrol, including a more systematic investigation of systemic exposure to resveratrol metabolites, their access to in vivo loci responsible for the benefits, and their disposition in target cells; an investigation of colon-luminal exposure to resveratrol and its metabolites for accessing colonic microbiota; and a multi-compound pharmacokinetic investigation of red wine.

Multi-compound pharmacokinetic research on Chinese herbal medicines: identifying potentially therapeutic compounds and characterizing their disposition and pharmacokinetics / 药学学报

Chinese traditional medicine has provided, since ancient times, a basis for health care and medicine to the Chinese nation and for China's national stability. Identification of the constituents responsible for therapeutic and undesired effects of Chinese herbal medicines is a type of key research facilitating the modernization of these medicines. For a complex Chinese herbal medicine, multi-compound pharmacokinetic research is a useful approach to identifying its constituents that are bioavailable (in their unchanged and/or metabolized forms) at loci responsible for the medicine's therapeutic action and to characterizing the compounds' disposition and pharmacokinetics related to the action. In addition, such pharmacokinetic research is also useful for identifying herbal compounds associated with the medicine's adverse effects and drug-drug interaction potential. Over the past decade, great advances have been achieved in the theory, methodology, associated techniques, and their application of such multi-compound pharmacokinetic research, which has become an emerging field in pharmacokinetics. In this perspective, we elaborate on the methodology, technical requirements, and key analytical techniques of multi-compound pharmacokinetic research on Chinese herbal medicines, describe research examples regarding investigation of pharmacokinetics and disposition of a class of bioactive herbal constituents (ginsenosides of Panax notoginseng root) and pharmacokinetics-based identification of potential therapeutic compounds from a dosed Chinese herbal medicine (LianhuaQingwen capsule), and discuss follow-up development for the multi-compound pharmacokinetic research.

Colecistogastrostomía guiada por ultrasonografía endoscópica en un paciente con cáncer pancreático: primer caso en Colombia (con video) / Endoscopic ultrasonography-guided cholecystogastrostomy in a patient with pancreatic cancer: the first case in Colombia (with video)

Resumen El tratamiento actual para la obstrucción biliar maligna es la derivación biliar no quirúrgica con propósito paliativo. La cirugía tiene indicaciones específicas en pacientes con patología maligna con propósito curativo. Sin embargo, la obstrucción duodenal y del conducto biliar intra o extrahepático no dilatado hace que esta cirugía y el procedimiento endoscópico guiado por ultrasonografía endoscópica (USE) sean difíciles de realizar. Presentamos nuestra experiencia con el primer caso en Colombia, un país latinoamericano del tercer mundo. Consistió en una colecistogastrostomía guiada por USE, a partir de la utilización de una endoprótesis luminal (Lumen-apposing metal stents, LAMS) (HOT AXIOS stent, Xlumena Inc.; Mountain View, CA, Estados Unidos) de 15 mm × 10 mm, en un paciente masculino con cáncer pancreático inoperable e invasión duodenal con conducto colédoco dilatado. La colecistogastrostomía guiada por USE podría ser considerada como una opción de más importancia para la descompresión biliar que el drenaje percutáneo, ya que es superior en términos de viabilidad técnica, seguridad y eficacia en casos específicos de estenosis ampular e invasión duodenal. Además, puede ser realizada en países del tercer mundo, cuando se cuenta con el entrenamiento y los instrumentos adecuados. La endoprótesis metálica totalmente recubierta, aplicada a luz (HOT AXIOS stent, Xlumena Inc.; Mountain View, CA, Estados Unidos), es ideal para la colecistogastrostomía guiada por USE, a fin de minimizar complicaciones como fugas biliares. Se necesitan estudios comparativos adicionales para validar los beneficios de esta técnica.

Abstract The current treatment of malignant biliary obstruction is non-surgical biliary diversion with palliative intent. The surgery having specific indications in patients with malignant pathology with curative intent. However, duodenal obstruction and non-dilated intra- or extrahepatic bile duct make these surgical and endoscopic procedures guided by EUS difficult. We present our experience with the first case in Colombia, a third-world country in Latin America, of a cholecystogastrostomy guided by endoscopic ultrasound (EUS) in a patient with unresectable pancreatic cancer and duodenal invasion with dilated common bile duct using a luminal stent (LAMS) (HOT AXIOS stent, Xlumena Inc.; Mountain View, CA, USA) 15 mm × 10 mm. EUS-guided cholecystogastrostomy should be considered as an option for biliary decompression of greater importance than percutaneous drainage since it is superior in terms of technical feasibility, safety and efficacy in specific cases of ampullary stenosis and duodenal invasion. In addition, it can be done in third world countries when it has the appropriate training and implements. The fully covered metal stent applied to light (HOT AXIOS stent, Xlumena Inc.; Mountain View, CA, USA) is ideal for EUS guided cholecystogastrostomy to minimize complications such as bile leakage. Additional comparative studies are needed to validate the benefits of this technique.

Correlación entre características clinicopatológicas e inmunohistoquímicas del cáncer de mama en mujeres argentinas / Correlation between clinicopathological and immunohistochemical characteristics of breast cancer in Argentine women

Introducción: El cáncer de mama se clasifica en 4 subgrupos moleculares de tumores. Estos factores biológicos junto al grado histológico, han tomado importancia en la nueva clasificación TNM ya que permite establecer pronósticos de sobrevida. Objetivo: Analizar la correlación entre los distintos subtipos moleculares de los carcinomas de mama con factores clínico-patológico, la presencia de metástasis axilares y en la re-estadificación de los tumores según la nueva Clasificación TNM de la AJCC. Material y método: Estudio observacional y descriptivo de series de casos, registrados en Registro de Cáncer de Mama (RCM), en Argentina entre los años 2006 a 2016. Resultados: La mayoría de los tumores fueron Luminales. Los estadios avanzados fueron en edades tempranas. El mayor compromiso axilar perteneció a HER2 neu positivos. Se consiguió re estadificar las pacientes aumentando el número de pacientes con estadios IA y IB y descendiendo los estadios IIA, IIIA, IIIB y IIIC. Conclusiones: De los subtipos moleculares con factores clinicopatológicos más desfavorables fueron los Triples Negativos y Her2 neu. La importancia de los factores biológicos a la hora de re estadificar los pacientes según TNM 8° edición, favorece los tratamientos conservadores y específicos contra el tumor evitando el sobre tratamiento e implican menores costos que las plataformas genómcias.

Introduction: Breast cancer is classified into 4 molecular subgroups. These biological factors, together with the histological grade, are important factors in the 8th edition of the TNM Classification, and allow establishing survival prognoses in patients with breast cancer. Objetive: The main objetive was to analyse the correlation between different molecular subtypes of breast carcinomas, the presence of axillary metastases and the correlation of tumours in the new TNM Classification. Material and method: Observational and descriptive restrospective study of case series registred in RCM, in Argentina between 2006 and 2016. Results: Most of the tumours were Luminals. The clinical presentation of advanced stages was more frequent at early ages. The molecular subtypes with the highest axillary involvement were HER2 neu tumours. We managed to re-stage the patients to the TNM Classification 8th edition, increasing the number of patients with stages IA and IB and decreasing the stage IIA, IIIA, IIIB and IIIC. Conclusions: Triples negative tumours were diagnosed in more advanced stages, according to the new TNM Classification, than the Luminals. The surgical decision was not modified according to the molecular subtype. We conclude the importance of biological factors when re-staging patients according to the new TNM Classification 8th edition because it increases the number of conservative treatments, and more targets treatment.

Quimioterapia Neoadyuvante en Tumores Luminales Experiencia del Hospital Oncológico Marie Curie / Neoadjuvant Chemotherapy in Luminal Tumors Experience of the Marie Curie Cancer Hospital

Introducción La quimioterapia neoadyuvante (QTn) es una herramienta de uso cada vez más frecuente en el tratamiento del cáncer de mama. su repercusión es objetivada a partir de parámetros clínicos (examen físico y estudios por imagen) y parámetros anatomo-patológicos sobre la pieza quirúrgica. Existe variabilidad en el impacto de la Qt según el subtipo molecular. Este estudio evalúa el grado de respuesta (clínica y patológica) a la QTn de las pacientes con cáncer de mama subtipo luminal y la tasa de cirugías conservadoras en este subgrupo. Objetivo Describir la tasa de respuesta clínica y patológica obtenida en el subgrupo de pacientes luminales y evaluar la tasa de conversión a cirugía conservadora luego del tratamiento neoadyuvante. Material y método Se analizaron 220 historias clínicas pertenecientes a pacientes que realizaron neoadyuvancia en el periodo 2014-2017 en el Servicio de Patología Mamaria del Hospital Oncológico Marie Curie. Se incluyeron 78 pacientes con diagnóstico de carcinoma invasor subtipo luminal A y B, Her 2 negativas. Se evaluó la tasa de respuesta clínica, patológica y la tasa de cirugía conservadora. Resultados Se clasificaron como Luminal A el 26.9% (n=21) de las 78 pacientes, y Luminal B el 73.1% (n=57). La distribución por tamaño tumoral fue: T1 en el 1.25% (n= 1); T2 en 46.1% (n= 36); T3 en 37.2% (n=29) y T4 en el 15.4% (n=12) de los casos. No presentaban compromiso axilar (N0) el 24.3% de las pacientes (n=19), y se vio afectación ganglionar el 75.5 % (n= 59). El Estadio clínico más frecuente fue el III A (32% = 25 pacientes). El 60.3% (47 pacientes) de los casos tenía indicación de mastectomía de inicio y el 39.7% (41 pacientes) eran candidatas a cirugía conservadora. Posterior a la quimioterapia, se indicaron cirugías conservadoras en el 52.6 % (n=41) y mastectomía en el 47.4% (n=37), con una tasa de conversión a cirugía conservadora del 24.4%. La respuesta clínica completa fue del 28.2% (n=22) y la respuesta patológica completa del 16.6%. Conclusión Se observó una respuesta clínica y patológica acorde a la experiencia de otros centros, sobre todo en el subtipo luminal B, con una alta tasa de conversión a cirugía conservadora del 24.4%. Esto nos permite considerar la quimioterapia neoadyuvante como una opción de tratamiento válida para aquellas pacientes con cáncer de mama subtipo luminal B- Her 2 negativa.

Introduction Neoadjuvant chemotherapy (QTn) is a tool that is increasingly used in the treatment of breast cancer. its repercussion is objectified based on clinical parameters (physical examination and imaging studies) and anatomo-pathological parameters on the surgical specimen. There is variability in the impact of Qt according to the molecular subtype. This study evaluates the degree of response (clinical and pathological) to the QTn of patients with luminal subtype breast cancer and the rate of conservative surgeries in this subgroup. Objective To describe the clinical and pathological response rate in the subgroup of luminous patients and to evaluate the conversion rate in a conservative surgery after neoadjuvant treatment. Material and method We will analyze 220 clinical records belonging to patients that developed during the 2014-2017 period in the Breast Pathology Service of the Marie Curie Oncology Hospital. We included 78 patients with a diagnosis of invasive carcinoma luminal subtype A and B, their 2 negative. The clinical and pathological response rate and the rate of conservative surgery in each group were evaluated. Results Luminal A was classified as 26.9% (n = 21) of the 78 patients, and Luminal B was 73.1% (n = 57). The distribution by tumor size was: T1 at 1.25% (n = 1); T2 at 46.1% (n = 36); T3 in 37.2% (n = 29) and T4 in 15.4% (n = 12) of the cases. There is no axillary involvement (N0) in 24.3% of the patients (n = 19), and the ganglion was affected 75.5% (n = 59). The most frequent clinical stage was III A (32% = 25 patients). Sixty-three percent (47 patients) of the cases had an initial mastectomy indication and 39.7% (41 patients) were candidates for conservative surgery. After chemotherapy, conservative surgeries were indicated in 52.6% (n = 41) and mastectomy in 47.4% (n = 37), with a conversion rate to conservative surgery of 24.4%. The complete clinical response was 28.2% (n = 22) and the complete pathological response was 16.6%. Conclusion A clinical and pathological response was observed according to the experience of other centers, especially in luminal subtype B, with a high conversion rate to conservative surgery of 24.4%. This allows us to consider neoadjuvant chemotherapy as a valid treatment option for those patients with luminal B-Her 2 negative breast cancer.

Manejo del cáncer de mama Estadio IV / Management of Stage IV breast cancer

El cáncer de mama Estadio IV se define como la diseminación de células tumorales más allá de la mama, la pared torácica y los ganglios linfáticos regionales. Globalmente, 5-10% de las mujeres tienen metástasis al momento del diagnóstico y hasta un 30% de aquellas con estadios tempranos al inicio desarrollará metástasis en algún momento. Se estima una mediana de sobrevida global en cáncer de mama metastásico de 3 años, con un intervalo que va desde pocos meses hasta muchos años, y una sobrevida a 5 años que ronda el 25%. Continúa siendo una enfermedad tratable pero no curable. Los objetivos terapéuticos en enfermedad metastásica principalmente son: prolongación de la sobrevida global y libre de enfermedad, disminución de síntomas y complicaciones asociadas al cáncer y mejoras en la calidad de vida de las pacientes. En la actualidad, estas metas son alcanzadas principalmente con la utilización de terapias sistémicas como la quimioterapia, la hormonoterapia o el uso de agentes biológicos. En algunas circunstancias, el tratamiento locorregional también contribuye a lograr estos objetivos. La elección del tratamiento sistémico está principalmente determinada por la biología tumoral, ya que esto permite el empleo de terapias dirigidas. En los tumores Luminales, deberá emplearse hormonoterapia, sola o en asociación con otros esquemas. En tumores her2+, se indicará, de ser posible, como primera línea de tratamiento doble bloqueo anti-her más quimioterapia. El subgrupo de peor pronóstico está representado por los tumores Triple Negativos, para los cuales no existen blancos terapéuticos dirigidos. En este caso, se utilizará quimioterapia. Se deberá usar terapia de mantenimiento luego de lograr el control de la enfermedad en tumores Luminales y her2+. El rol del tratamiento locorregional en cáncer de mama metastásico continúa siendo un tema de debate. Actualmente, algunos estudios sugieren que podrían obtenerse algunos beneficios, aunque aún hacen falta más datos para sostener su indicación. Deberá garantizarse un abordaje multidisciplinario y un seguimiento cercano de estas pacientes, con el fin de valorar la respuesta al tratamiento, la aparición de toxicidad inaceptable y las condiciones de calidad de vida

Stage IV breast cancer is defined as the spread of tumor cells beyond the breast, chest wall, and regional lymph nodes. Globally, 5-10% of women have metastases at diagnosis, and up to 30% of those with early stages of onset will develop metastases at some point. A median overall survival in metastatic breast cancer of 3 years is estimated, with an interval ranging from a few months to many years, and a 5-year survival of around 25%. It remains a treatable but not curable disease. The therapeutic goals in metastatic disease are mainly: prolongation of global and disease-free survival, decrease in symptoms and complications associated with cancer, and improvements in the quality of life of patients. At present, these goals are mainly achieved with the use of systemic therapies such as chemotherapy, hormonal therapy or the use of biological agents. In some circumstances locoregional treatment also contributes to achieving these goals. The choice of systemic treatment is mainly determined by tumor biology, since this allows the use of targeted therapies. In Luminal tumors, hormone therapy should be used, alone or in association with other schemes. In her2+ tumors, double blocking anti-her plus chemotherapy will be indicated if possible as the first line of treatment. The worst prognosis subgroup is represented by Triple Negative tumors for which there are no targeted therapeutic targets. In this case chemotherapy will be used. Maintenance therapy should be used after achieving control of the disease in Luminal tumors and her2+. The role of locoregional treatment in metastatic breast cancer continues to be a matter of debate. Currently some studies suggest that some benefits could be obtained although more data are still needed to support its indication. A multidisciplinary approach and close monitoring of these patients should be guaranteed in order to assess the response to treatment, the appearance of unacceptable toxicity and quality of life conditions

Pneumatosis cystoides intestinalis - an incidental finding with unpredictable evolution / Pneumatose cistoide intestinal - um achado incidental com evolução imprevisível

Abstract Pneumatosis cystoides intestinalis is an uncommon disease with unknown etiology characterized by the presence of multiple gas-filled cysts within the submucosa or subserosa of the intestinal wall. Pneumoperitoneum and/or intestinal perforation are complications that may be associated with pneumatosis cystoides intestinalis. The patients are often prone to misdiagnosis or mistreatment.We are presenting a case of pneumatosis cystoides intestinalis in a 42 year-old woman affected by peritoneal free air and numerous, diffuse, bubble-like intramural gas collections into the jejunum and ileum, showed in CT-enterography images. The woman had a carcinoid tumor located in jejunum two years ago, treated with enterectomy. Recent complaints of nonspecific symptoms of abdominal discomfort and diarrhea motivated the realization of CT scan, serum chromogranin and urine 5-hidroxindolacetic acid for hypothesis of tumor carcinoid recurrence withdraw. The only change found was the presence of pneumatosis cystoides intestinalis in CT-enterography images without intestinal necrosis, bleeding or evident obstruction. For that reason no surgical procedure was realized and the patient stayed on surveillance. Actually, the patient complaints are sporadic abdominal discomfort, without pneumatosis cystoides intestinalis clinical evidence. Conclusion: The treatment plan of patient with PCI depends on underlying cause and clinical condition severity. When conservative treatment is adopted the clinical evolution of pneumatosis cystoides intestinalis is unpredictable and can even disappear in an indeterminate number of patients.

Resumo A pneumatose cistoide intestinal é uma doença incomum, de etiologia desconhecida, caracterizada pela presença de múltiplos cistos preenchidos com gás na submucosa ou subserosa da parede intestinal. O pneumoperitoneu e/ou a perfuração intestinal são complicações que podem estar associadas à pneumatose cistoide intestinal. Os pacientes geralmente estão sujeitos a erros de diagnóstico ou de tratamento.Apresentamos um caso de pneumatose cistoide intestinal em paciente do sexo feminino, 42 anos de idade, com ar livre peritoneal e numerosas coleções gasosas intramurais, difusas e semelhantes a bolhas no jejuno e íleo, visualizados em imagens de enterografia por tomografia computadorizada (TC). Há dois anos, a paciente teve um tumor carcinoide localizado no jejuno que foi tratado com enterectomia. As queixas recentes de sintomas inespecíficos, desconforto abdominal e diarreia motivaram a realização da TC e exame de cromogranina sérica e ácido 5-hidroxindolacético na urina para excluir a hipótese de recorrência do tumor carcinoide. A única alteração encontrada foi a presença de pneumatose cistoide intestinal em imagens de enterografia por TC sem necrose intestinal, sangramento ou obstrução evidente. Por esse motivo, nenhum procedimento cirúrgico foi realizado, e a paciente permaneceu em observação. Atualmente, a queixa da paciente é de desconforto abdominal esporádico, sem evidência clínica de pneumatose cistoide intestinal. Conclusão: O plano de tratamento de pacientes com PCI depende da causa subjacente e da gravidade da condição clínica. Quando o tratamento conservador é adotado, a evolução clínica da pneumatose cistoide intestinal é imprevisível e pode até desaparecer em alguns pacientes.

Histomorphometric changes of gonads in male guinea pigs after thymectomy

Introduction: The presence of the thymus gland during early life is essential for the normal development ofimmune system and as well as proper maturation of the hypothalamic – pituitary- gonadal axis. This study wasto investigate the influence of thymus gland on male reproductive function.Aim: The aim of this study to investigate the effect of thymectomy on Morphometric changes of gonads inneonatal, prepubertal and pubertal thymectamized male guinea pigs.Material and Methods: In this study, a total of thirty male guinea pigs, thymectamized (n-6) and sham-operated(n-4) were studied in each group. The comparison of diameter of seminiferous tubules, luminal diameter andepithelial thickness in the thymectamized and sham operated male guinea pigs.Results: No Significant changes in the morphometry of seminiferous tubules of testis in thymectamized maleguinea pigs compared to the sham-operated guinea pigs in all age groups. These results suggest that thymectomyhad no detrimental effects on reproductive system in males at any intervals.

Histomorphometry of human vermiform appendix

Background: Acute Appendicitis is one of the most common acute abdominal conditions. Advances in modern radiographic imaging have improved diagnostic accuracy, however the diagnosis of appendicitis remains essentially an enigmatic challenege. Though much work has been done on morphometry but there is less work done on variation of histomorphometric features of appendix. Hence the study was carried out by keeping the following objectives in mind. Aim was to study the general histomorphology and measure the histomorphometric parameters of human vermiform appendix. And also, to study diagnostic significance of histomorphology and histomorphometric parameters in causing appendicitis.Methods: The study was conducted in the Department of Anatomy. Specimens of appendix were obtained from embalmed cadavers. Serial sections were taken at different levels and slides were prepared. The slides were then examined using Nikon Trinocular Research microscope under magnification power of 40x for various parameters, after staining with H&E.Results: The mean luminal diameter varied from 1.32±0.65mm at base to 1.22±0.72mm from base. Diffuse lymphatic tissue was seen in both mucosa and sub-mucosa.Conclusions: Definitely there is a relationship between lymphoid follicle diameter and mucosal-serosal thickness on one hand and that between the luminal diameter and lymphoid follicle diameter on the other hand. Since our study was restricted to geriatric age group so studies need to be done in different age groups to highlight any further relationship.

Bases moleculares da absorção de nutrientes, tamponamento e fluxos de fluídos no intestino médio de Musca domestica / Molecular bases of nutrient absorption, buffering and fluid fluxes in the midgut of Musca domestica

O intestino dos insetos representa uma interface pouco protegida dos agentes externos. A identificação dos mecanismos moleculares envolvidos nos processos fisiológico-digestivos permite encontrar alvos potenciais para o controle de insetos. As moléculas envolvidas na absorção de nutrientes, tamponamento e geração de fluxos de água no intestino médio do inseto-modelo Musca domestica (Diptera Cyclorrhapha) foram identificadas. Para isso, foi feita uma análise da expressão gênica ao longo do intestino médio, a identificação e anotação de proteínas por bioinformática, a confirmação da localização apical das proteínas por análise proteômica de membranas microvilares purificadas e a determinação do papel de algumas das proteínas através de experimentos in vivo utilizando diferentes dietas, corantes e inibidores. A acidificação da região média é consequência da atividade anidrase carbônica que gera prótons que são bombeados por uma H+ V-ATPase apical acompanhados por cloreto transportado por um simporter K+Cl-. O K+ é recuperado por um canal de K+ e a homeostase dos cátions mantida pela Na+/K+-ATPase basolateral. O bicarbonato é eliminado basolateralmente em troca por cloreto por um antiporter. A acidificação é regulada diretamente por um antiporter Na+/H+ e indiretamente por uma proteína envolvida na homeostase do cobre. O muco protetor da região média é tamponado com bicarbonato gerado por uma anidrase carbônica com âncora de GPI e transportado por um antiporter Na+HCO3-/H+Cl-. O excesso de ácido é eliminado por um antiporter Na+/H+ situado na membrana basolateral. A alcalinização da região posterior ocorre pelo transporte apical de NH3 que sequestra os prótons luminais gerando amônio, junto à remoção de prótons em simporte com aminoácidos e peptídeos. A acidificação intracelular, consequência da entrada de aminoácidos com prótons, é regulada por uma H+ V-ATPase basolateral. A geração de fluxos de água é consequência da atividade conjunta de simporters NKCC e KCC ajudados pelas aquaporinas. A inibição dos simporters com inibidores específicos mostrou que o contrafluxo de água está envolvido na reciclagem da enzima tripsina. Por último, o principal lugar de absorção nutrientes no intestino médio é a região posterior, a exceção do cobre que é absorvido na região média

The gut of insects is a less protected interphase against external agents. The identification of the molecular mechanisms involved in physiological-digestive processes allows one to find potential targets for insect control. The molecules involved in nutrient absorption, buffering and fluid fluxes in the midgut of the insect-model M. domestica (Diptera Cyclorrhapha) were identified. For this, gene expression along the midgut was analyzed; proteins were identified and annotated by bioinformatics; apical localization of proteins was confirmed by proteomics of purified microvillar membranes; the role of proteins was confirmed by in vivo experiments using different diets, dyes and inhibitors. Middle midgut acidification occurs by the action of an apical H+ V-ATPase with protons coming from carbonic anhydrase activity accompanied by chloride transported with potassium by a K+Cl- symporter. Potassium is recovered by a potassium channel, and cation homeostasis maintained by a basolateral Na+/K+-ATPase. Acidification is directly regulated by a Na+/H+ antiporter and indirectly by a copper homeostasis protein. Mucus protecting epithelium is neutralized with bicarbonate generated by a GPI-ancored carbonic anhydrase and transported by a Na+HCO3-/H+Cl- antiporter. Intracellular acidification is avoided by a basolateral Na+/H+ antiporter. Posterior midgut alkalization occurs by the action of an apical ammonia transporter and proton amino acid (and peptide) symporters. Intracellular acid is eliminated by a basolateral H+ V-ATPase. Fluid fluxes are generated by K+Cl- and Na+Cl-Cl- symporters helped by aquaporins. Inhibition of these symporters showed that the countercurrent flux of water allows trypsin recycling. Finally, posterior midgut is the main location of nutrient absorption, except for copper which is absorbed in the middle midgut

Histomorphometric Analysis of Umbilical Arteries in Preeclampsia

Introduction: Preeclampsia is a pregnancy‑related hypertensive disorder complicated with placental hypoxia and resistance. The hypoxia and hypertension can induce changes in the morphometric parameters of umbilical cord and its vessels that can further affect the blood flow to the fetus. Subjects and Methods: Umbilical cords were collected from new-borns of preeclamptic and normal mothers, length and diameter were measured. Further, cords were processed for histological examination. The diameter, luminal area and wall thickness of umbilical arteries were measured. Results: A shorter and narrower cord was observed in preeclampsia. The umbilical arteries in preeclamptic cases were dilated, whereas statistically significant changes were not observed in the thickness of wall. Conclusion: Dilated umbilical arteries would be an adaptation to the affected babies so as to ensure reduced resistance for fetal circulation.

Structural and Functional Features on Quantitative Chest Computed Tomography in the Korean Asian versus the White American Healthy Non-Smokers

OBJECTIVE: Considering the different prevalence rates of diseases such as asthma and chronic obstructive pulmonary disease in Asians relative to other races, Koreans may have unique airway structure and lung function. This study aimed to investigate unique features of airway structure and lung function based on quantitative computed tomography (QCT)-imaging metrics in the Korean Asian population (Koreans) as compared with the White American population (Whites). MATERIALS AND METHODS: QCT data of healthy non-smokers (223 Koreans vs. 70 Whites) were collected, including QCT structural variables of wall thickness (WT) and hydraulic diameter (Dh) and functional variables of air volume, total air volume change in the lung (ΔVair), percent emphysema-like lung (Emph%), and percent functional small airway disease-like lung (fSAD%). Mann-Whitney U tests were performed to compare the two groups. RESULTS: As compared with Whites, Koreans had smaller volume at inspiration, ΔVair between inspiration and expiration (p < 0.001), and Emph% at inspiration (p < 0.001). Especially, Korean females had a decrease of ΔVair in the lower lobes (p < 0.001), associated with fSAD% at the lower lobes (p < 0.05). In addition, Koreans had smaller Dh and WT of the trachea (both, p < 0.05), correlated with the forced expiratory volume in 1 second (R = 0.49, 0.39; all p < 0.001) and forced vital capacity (R = 0.55, 0.45; all p < 0.001). CONCLUSION: Koreans had unique features of airway structure and lung function as compared with Whites, and the difference was clearer in female individuals. Discriminating structural and functional features between Koreans and Whites enables exploration of inter-racial differences of pulmonary disease in terms of severity, distribution, and phenotype.

Luminal B. Factor pronóstico y predictivo del Ki67 / Luminal B. Prognostic and predictive factor of Ki67

Introducción El cáncer de mama es una enfermedad heterogénea; tumores con factores pronósticos similares presentan diferente evolución, lo que hace suponer que la diferencia es molecular. El antígeno de proliferación celular Ki67 es un factor clave que representa la actividad mitótica celular. Objetivos Analizar el subtipo Luminal B y el valor del Ki67, evaluando su relación con los factores pronósticos y predictivos clásicos, y determinar su utilidad para subclasificar grupos moleculares en función del mismo. Material y métodos Estudio descriptivo, retrospectivo, analítico observacional. Se revisaron 520 fichas de patología mamaria pertenecientes al Hospital Churruca y al Sanatorio Corporación Médica General San Martín, en el período comprendido entre enero 2010-enero 2015. Fueron analizadas 82 pacientes subtipo Luminal B, con Ki67 elevado. Resultados La mediana de expresión del Ki67 fue de 25,9% y del 34% en las pacientes recaídas. Discusión Se observó relación proporcional del Ki67 con el tamaño tumoral y el grado histológico. Conclusiones El Ki67 debe ser analizado en la práctica diaria por patólogos expertos, a fin de predecir el comportamiento frente a tratamientos adyuvantes de una manera más certera, adecuando la terapéutica a cada paciente.

Introduction Breast cancer is a heterogeneous disease; tumors with similar prognostic factors have different evolution, which suggests that the difference is at the molecular level. The proliferation antigen Ki67 is a key factor that represents the cell mitotic activity. Objectives Analyze Luminal B subtype and the value of Ki67, evaluating its relationship with prognostic and predictive factors conventionally used. Determine its usefulness for subclassified different molecular groups. Matherials and method Observational analytical retrospective study. We reviewed 520 breast cancer files belonging to Churruca Hospital and Sanatorio Corporación Médica General San Martín in the period between January 2010- January 2015. We analyzed 82 patients Luminal B subtype with hight Ki67. Results The median expression of Ki67 was 25.9 % and 34% in patients with relapsed. Discussion We found proportional relationship between the value of Ki67 with tumor size and histologic hight grade. Conclusions The Ki67 must be analyzed in daily practice validated by expert pathologists in late predict behavior towards adjuvant treatments in a more accurate way available, adapting to each patient therapeutic methods.

Differences in expression profiles of circular RNA between luminal breast cancer cells and normal breast cells / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the differences in the expression profiles of circular RNA (circRNA) between luminal breast cancer cells and normal breast cells.</p><p><b>METHODS</b>Total RNA extracted from luminal breast cancer cells MCF7 and normal breast cells MCF10A was digested with Rnase R to remove linear RNAs and enrich circRNAs. The enriched circRNAs were amplified and transcribed into fluorescent cRNAs using a random priming method, and were hybridized onto the circRNA hybridization array. The circRNA expression profiles of MCF7 and MCF10A cells were analyzed using Agilent Feature Extraction software. Quantile normalization and subsequent data processing were performed, and volcano plot filtering and hierarchical clustering were utilized to analyze the circRNA expression patterns. The expressions of 3 circRNAs with significant log fold changes were validated using qPCR.</p><p><b>RESULTS</b>The hybridization array data revealed significant differences in the circRNA expression profiles between MCF7 and MCF10A cells. Compared with those of MCF10A cells, the 12910 circRNAs expressed in MCF7 cells showed 5964 up-regulated, 81 consistently regulated, and 6865 down-regulated circRNAs; 343 circRNAs showed a log fold change by more than 2 folds, among which 213 circRNAs were up-regulated and 130 were down-regulated. Nine circRNAs showed differential expressions by more than 2 folds, including 8 up-regulated ones, namely hsa_circRNA_061260 (6.02 folds), hsa_circRNA_103933 (5.96 folds), hsa_circRNA_005239 (5.84 folds), hsa_circRNA_100689 (5.69 folds), hsa_circRNA_004087 (5.60 folds), hsa_circRNA_104420 (5.25 folds), hsa_circRNA_104421 (5.13 folds) and hsa_circRNA_101222 (5.03 folds); only one circRNA was down-regulated, namely hsa_circRNA_104864 (5.09 folds). The expressions of hsa_circRNA_100689, hsa_circRNA_005239 and hsa_circRNA_104864 were further validated by qPCR, which yielded consistent results with the microarray data.</p><p><b>CONCLUSIONS</b>The circRNA expression profiles differ significantly between luminal breast cancer cells and normal breast cells. These differentially expressed circRNAs may serve as potential novel targets for the diagnosis of luminal breast cancer.</p>

Observation on curative effects of neoadjuvant chemotherapy for different subtypes of Luminal B breast cancer and analysis on its prognosis / 吉林大学学报(医学版)

Objective: To investigate the differences in the curative effects of neoadjuvant chemotherapy (NAC) for different subtypes of Luminal B breast cancer and its prognosis, and to discuss the clinical treatment characteristics of different subgroups. Methods: A total of 246 cases of Luminal B like breast cancer patients who completed the projected NAC courses and surgical treatment were selected. All the biopsy specimens before treatment were positive for estrogen receptot (ER). According to the expressions of progesterone receptor (PR), human epidermal growth factor-2 (Her-2) and cell proliferation nuclear antigen Ki-67, 246 cases of Luminal B breast cancer patients were divided into 3 subgroups. A subgroup (PR low expression group), Her-2 negative and PR0.05). There were significant differences in the lymph node metastasis rate among three subgroups (P=0.018), and the lymph node metastasis rate was the highest in A subgroup among three subgroups. There were no significant differences in the clinical response and pathological response among three subgroups (P= 0.123, P=0.06). 8.5% 21/246) patients achieved the pathological complete response (pCR); the rates of pCR in three subgroups had statistically significant difference (P=0.009); the rate of pCR in C subgroup was the highest, and the rate of pCR in B subgroup was the lowest. The Log-Rank test of the survival curves of three subgroups had not statistically significant difference (P=0.216), but the 3-year disease-free survival (DFS) and 5-year DFS of the patients in B subgroup were slightly higher than those in other two groups. The DFS of the patients in C subgroup was longer than that of the patients with Her-2 overexpression breast cancer at the same period, and the difference was statistically significant (P= 0.047). Conclusion: Her-2 positive Luminal B breast cancer is more likely to achieve pCR in NAC and the prognosis is better than Her-2 overexpressing breast cancer. The patients with high expression of PR in Luminal B breast cancer patients have a tend of overall survival advantage compared with the patients with PR low expression and Her-2 positive expression.