Diagnóstico de precisão das lesões mamárias / Accurate diagnosis of breast lesions

PONTOS-CHAVE As lesões mamárias compreendem uma ampla variedade de diagnósticos que apresentam comportamentos diversos. As lesões mamárias podem ser classificadas como lesões benignas, de potencial de malignidade indeterminado (B3), carcinoma in situ e carcinoma invasor. Na era da medicina personalizada, individualizar e obter um diagnóstico preciso faz grande diferença no desfecho final da paciente, principalmente no caso do câncer de mama. Exames de imagem direcionados e de qualidade, métodos de biópsia adequadamente selecionados e análises de anatomopatologia convencional, imuno-histoquímica e até molecular são determinantes no diagnóstico e no manejo das pacientes.

Research progress on traditional Chinese medicine compounds combined with external therapy in treatment of hyperplasia of mammary glands / 中国中药杂志

Hyperplasia of mammary glands is a benign breast disease with disordered breast structure. Nowadays, the incidence rate of breast hyperplasia in women is increasing year by year, and the etiology is related to the imbalance of estrogen and progesterone in the body. The symptoms include breast pain, breast nodules, or nipple discharge, which can develop into breast cancer in the context of psychological pressure. Therefore, it is timely and effectively necessary for people to treat the symptoms. At present, traditional Chinese medicine(TCM) often treats breast hyperplasia by oral drug, external application, acupuncture, moxibustion, and massage, while western medicine often uses hormone therapy or surgery. TCM can regulate hormone levels to treat breast hyperplasia. Acupuncture, moxibustion, and other methods can stimulate acupoints to reduce breast lumps. However, since TCM is easy to produce hepatorenal toxicity after long-term use and simple external treatment is slow to take effect, rapid and effective treatment is difficult to be achieved. Although western medicine can inhibit the disease, it is easy to produce toxic and side effects if taken for a long time. In addition, surgery can only remove the focus and the recurrence rate is high. Some studies have found that the combination of oral and external use of TCM compounds has a significant effect, with mild toxic and side effects, few adverse reactions, and a low recurrence rate. Based on the relevant literature in recent years, this article reviewed the combination of oral and external treatment of TCM in the treatment of hyperplasia of mammary glands, discussed the effectiveness, clinical evaluation indexes, and mechanism, and pointed out the existing shortcomings to explore a comprehensive therapy worthy of clinical application.

Mechanism of blood-activating and mass-dissipating Chinese patent medicine against hyperplasia of mammary glands and use with other medicine: a review / 中国中药杂志

Caused by endocrine disorder, hyperplasia of mammary glands(HMG) tends to occur in the young with increasing incidence, putting patients at the risk of cancer and threatening the health of women. Therefore, the prevention and treatment of HMG is attracting more and more attention. Amid the modernization of traditional Chinese medicine(TCM), many scholars have found that Chinese patent medicine has unique advantages and huge potential in treatment of endocrine disorder. Particularly, Chinese patent medicine with the function of blood-activating and mass-dissipating, such as Xiaojin Pills and Xiaozheng Pills, has been commonly used in clinical treatment of HMG, which features multiple targets, obvious efficacy, small side effect, and ease of taking and carrying around. Clinical studies have found that the combination of Chinese patent medicine with other medicine can not only improve the efficacy and relieve symptoms such as hyperplasia and pain but also reduce the toxic and side effects of western medicine. Therefore, based on precious pharmacological research and clinical research, this study reviewed the mechanisms of blood-activating mass-dissipating Chinese patent medicine alone and in combination with other medicine, such as regulating levels of in vivo hormones and receptors, promoting apoptosis, inhibiting angiogenesis, improving hemorheology indexes, enhancing immunity, and boosting antioxidant ability. In addition, limitations and problems were summarized. Thereby, this study is expected to lay a theoretical basis for the further study and clinical application of blood-activating mass-dissipating Chinese patent medicine alone or in combination with other medicine against HMG.

Representações sociais de puérperas sobre as mamas no aleitamento / Representaciones sociales de puérperas sobre la pechos en lactancia / Social representations of puerperals about the breast in breastfeeding

Objetivo: Apreender representações sociais de puérperas sobre as mamas no período do aleitamento. Método: Pesquisa qualitativa, fundamentada na teoria das representações sociais. Utilizou-se o teste de associação livre de palavras, aplicado a 95 puérperas num Centro de Parto Normal de Salvador-Ba, no período de novembro de 2017 a fevereiro de 2018. Realizou-se a análise da estrutura das representações sociais a partir da árvore de similitude das evocações livres. Resultados: As representações sociais das puérperas sobre as mamas são marcantemente a dor e o tamanho, influenciadas por elementos periféricos que envolvem o ato de amamentar e a saúde, estando associadas as suas crenças, conhecimentos e valores afetivos. As participantes reconhecem que as mamas são partes importantes do corpo que requerem cuidado cotidianamente. Conclusão: Os achados corroboram para novos olhares para subjetividades que envolvem o aleitamento, podendo nortear práticas de cuidado em saúde que colaborem para satisfação enquanto nutriz.(AU)

Objective: To apprehend social representations of postpartum women about their breasts during the breastfeeding period. Method: Qualitative research, based on the theory of social representations. The free word association test was used, applied to 95 postpartum women in a Normal Delivery Center in Salvador-Ba, from November 2017 to February 2018. The analysis of the structure of social representations was carried out from the tree of similarity of free evocations. Results: The postpartum women's social representations about the breasts are markedly pain and size, influenced by peripheral elements that involve the act of breastfeeding and health, being associated with their beliefs, knowledge and affective values. Participants recognize that the breasts are important parts of the body that require daily care. Conclusion: The findings corroborate new perspectives on subjectivities that involve breastfeeding, which may guide health care practices that contribute to satisfaction as a nursing mother.(AU)

Objetivo: Aprender las representaciones sociales de las mujeres posparto sobre sus senos durante el período de lactancia. Método: Investigación cualitativa, basada en la teoría de las representaciones sociales. Se utilizó la prueba de asociación libre de palabras, aplicada a 95 puérperas en un Centro de Parto Normal en Salvador-Ba, de noviembre de 2017 a febrero de 2018. El análisis de la estructura de las representaciones sociales se realizó a partir del árbol de similitud de evocaciones libres. Resultados: Las representaciones sociales de las mujeres posparto sobre las mamas son marcadamente dolorosas y de tamaño, influenciadas por elementos periféricos que involucran el acto de la lactancia materna y la salud, estando asociadas a sus creencias, conocimientos y valores afectivos. Los participantes reconocen que los senos son partes importantes del cuerpo que requieren cuidados diarios. Conclusión: Los hallazgos corroboran nuevas perspectivas sobre subjetividades que involucran la lactancia materna, las cuales pueden orientar prácticas de cuidado de la salud que contribuyan a la satisfacción como madre lactante.(AU)

Establishment and comparison of two methods to produce a rat model of mammary gland hyperplasia with hyperprolactinemia

Abstract This study aimed to establish and compare models of mammary gland hyperplasia (MGH) with hyperprolactinemia (HPRL) using two different methods. The models provide information on the relationship between mammary gland hyperplasia and associated hormones. Model A was constructed using intramuscular injections of estradiol benzoate injection (EBI), followed by progesterone (P), and then metoclopramide dihydrochloride (MDI). Model B was designed by administering MDI, follow by EBI, and then P intramuscularly. Model B showed higher MGH progression compared with model A. Notably, increase in estradiol (E2) was negatively correlated with prolactin (PRL) secretion. However, PRL levels in model B were significantly higher compared with the levels in model A. Estrogen (ER), prolactin receptor (PRLR), and progesterone receptor (PR) mRNA and protein expression levels in model B rats were positively correlated with changes in the corresponding hormone levels. However, E2, P, and PRL levels in model A showed no direct relationship with levels of the mRNAs of related hormones and protein expression levels. Our results suggest that model B is an appropriate model of MGH with HPRL that can be used to perform further studies about the interactions of the E2, P, and PRL hormones in this disorder.

Identificação das proteínas interagentes de Yes-Associated protein (YAP), um efetor da via Hippo, em células epiteliais mamárias expostas à matriz extracelular rica em laminina / Identification of interacting proteins of Yes-Associated Protein (Yap) in mammary epithelial cells exposed to laminin-rich extracellular matrix

A sinalização da matriz extracelular (MEC) é essencial para a determinação do destino e comportamento de células epiteliais da glândula mamária. Entretanto, pouco é conhecido sobre os mecanismos moleculares envolvidos nesse processo. A via Hippo, uma cascata de sinalização que participa da regulação de diversos comportamentos celulares, incluindo o tamanho de órgãos, parece ser uma importante candidata a mediadora sinalização da MEC. Resultados preliminares do laboratório indicam que a arquitetura tecidual e a membrana basal, componente da MEC de epitélios e outros tecidos, influenciam a localização, concentração e atividade de YAP, uma proteína efetora da via Hippo, em células epiteliais mamárias. Neste contexto, o objetivo deste trabalho foi identificar as proteínas que interagem com Yap (ortólogo de YAP em camundongo) nas células epiteliais da glândula mamária em resposta à membrana basal. Foram utilizadas células EpH4, uma linhagem mamária não-tumoral murina, como modelo de diferenciação funcional e formação de ácinos em um ensaio de cultura tridimensional (3D). O tratamento de estruturas multicelulares 3D pré-formadas em placas nãoadesiva com uma matriz rica em laminina (lrECM) alterou a localização e o padrão subcelular de Yap, assim como a expressão gênica de membros da via Hippo e dos alvos de Yap, mas não alterou a expressão das proteínas da via em nível de proteína. O ensaio de co-imunoprecipitação (CoIP) seguida de análise por espectrometria de massas identificou um conjunto diferencial de proteínas que interagem com Yap na fração citoplasmática de células EpH4 cultivadas na ausência ou na presença de lrECM em um modelo de ECM-overlay. Uma análise realizada junto à database KEGG Pathways revelou que os possíveis interagentes Yap nas células cultivadas não-tratadas com lrECM participam de processos relacionados à proteólise mediada por ubiquitina, enquanto nas células expostas à lrECM os possíveis interagentes estão associados a processos metabólicos e são especialmente proteínas-chave do metabolismo de lipídios. A busca na plataforma de redes de interação STRING não identificou trabalhos que destaquem a interação de Yap com estas proteínas. A plataforma Vizit indica a participação de Yap em processos relacionados à síntese e atividade de lipídios e hormônios, o que reforça as evidências de que está pode ser uma nova função de Yap ainda não explorada em detalhes. A fim de se obter resultados complementares à CoIP, padronizamos o ensaio de identificação por biotinilação dependente de proximidade (BioID) em células embrionárias de rim humano da linhagem 293FT. As proteínas isoladas por pulldown foram identificadas por espectrometria de massas e uma análise junto à database Gene Ontology indicou que os possíveis interagentes de Yap nestas células são em sua maioria proteínas relacionadas à via Hippo, o que reforça a robustez do ensaio. Nós pretendemos transpor este sistema para as células EpH4. A expectativa é que, em conjunto, estes resultados nos orientem em projetos futuros para compreender os mecanismos de sinalização da MEC na morfogênese e diferenciação da glândula mamária

Extracellular matrix (ECM)-signaling is crucial for determination of epithelial cell fate and behavior in the mammary gland. However, little is known about the molecular mechanisms involved in these processes. The Hippo pathway, a signaling cascade involved in the regulation of several cellular processes, including organ size, seems to be an important candidate as a mediator of this signaling. Our preliminary results indicate that the tissue architecture and the basement membrane, an ECM component of epithelia and other tissues, influence the location, level and activity of YAP, an effector of the Hippo pathway. In this context, the goal of this work was to identify the proteins that interact with Yap (ortholog of YAP in mouse) in mammary epithelial cells in response to the basement membrane. We used EpH4 cells, a nontumoral murine mammary cell, in a functional differentiation and acini-forming in tridimensional (3D) culture assay. Treatment of 3D multicellular structures pre-formed on nonadhesive plates with a laminin-rich extracellular matrix (lrECM) altered the subcellular localization and pattern of Yap, as well as gene expression of Hippo pathway proteins and Yap targets, but did not altered the expression of the pathway members at the protein level. Coimmunoprecipitation (CoIP) followed by mass spectrometry analysis identified a differential set of proteins interacting with Yap in cytoplasmic fractions of EpH4 cells in the absence or presence of lrECM in an ECM-overlay culture model. An analysis performed with the KEGG Pathways database revealed that putative Yap interactors in non-treated cells participate in processes related to ubiquitin-mediated proteolysis, whereas in cells exposed to lrECM Yap interactors are associated to metabolic processes and are mainly key-proteins of metabolism of lipids and carbohydrates. A search in interaction networks platform STRING did not identify previous works that showing the interaction of Yap with these proteins. Vizit platform indicated the participation of Yap in processes related to the synthesis and activity of lipids and hormones, which reinforces the evidences that Yap can play a novel poorly explored role. To obtain complementary results to CoIP, we devised the proximity-dependent biotinylation identification (BioID) assay on embryonic renal cells of 293FT cell line. Pulldown-isolated proteins were identified by mass spectrometry and an analysis performed with Gene Ontology database revealed that putative Yap interactors are Hippo pathway-related proteins, which reinforces the robustness of the assay. We intend to transpose this system to the EpH4 cells. We expect that, together, these results will guide us in future projects to understand the signaling mechanisms of ECM in mammary gland morphogenesis and differentiation

Stem cell analysis with intraductally treated mammary epithelial cells

PURPOSE: The activity of mammary stem cells (MaSCs) is essential to mammary growth, differentiation and regeneration in cycles of pregnancy, lactation, and involution. The capability to recruit the mammary gland through the cycles is attributed to stem cells. It was shown that the intraductal (i.duc) injection of pegylated liposomal doxorubicin (PLD) to multiparous FVB/N mice was associated with a significantly reduced outgrowth potential of mammary gland cells. We have explored i.duc PLD's effect on stem cell number and function in mouse mammary gland and aldehyde dehydrogenase (ALDH)'s availability as a mouse MaSC marker.METHODS: The total mammary epithelium was purified from 6 to 8-month-old FVB/N control and i.duc PLD-administered mice treated twice and analyzed by flow cytometry and limiting dilution cleared mammary fat pad transplants.RESULTS: There was no significant difference in the proportions of stem cell-enriched population (CD49(fhigh)CD24(med)) between control and i.duc PLD-treated groups. However, we found a significant reduction in the outgrowth potential of CD49(fhigh)CD24(med) and CD49(fhigh)CD24(med)ALDH(+) cells from i.duc PLD-treated mammary glands. We discovered that adding ALDH to CD49(fhigh)CD24(med) had the possibility of better marker selection for MaSC of mice.CONCLUSION: We present i.duc administration of PLD to reduce MaSC function, but not the number; and ALDH activity may add further selection of MaSCs to CD49f CD24 in mouse mammary glands. Screening of chemotherapeutic drugs or other natural products by this method of stem cell analysis may provide safe i.duc treatment in breast cancer.

Hidradenoma Papilliferum of the Anus: A Report of 2 Cases and Review of the Literature

Hidradenoma papilliferum is a rare benign cystic tumor that originates from apocrine glands or anogenital mammary glands. Here, we describe 2 cases of hidradenoma papilliferum of the anus. Two female patients aged 39 and 35 presented with perianal masses with hemorrhoids. The patients underwent hemorrhoidectomy and excision of the lesion. Histopathology confirmed the masses as hidradenoma papilliferum. The postoperative course was uneventful for both patients, and there were no recurrences after 18 and 12 months of follow-up, respectively. Proctologists should consider hidradenoma papilliferum in their differential diagnosis of benign anal tumors. Surgical excision is necessary for diagnosis and treatment of hidradenoma papilliferum.

Histopathological and microbiological findings in buffalo chronic mastitis: evidence of tertiary lymphoid structures

Buffalo mastitis is an important economic problem in southern Italy, causing qualitative/quantitative alterations in milk and resulting in economic losses due to the sub-clinical course and chronic evolution. We investigated 50 udders of slaughtered buffaloes and subjected them to effectual microbiological screening to evaluate macro and microscopic mammary gland changes, immune-characterize the cell infiltrates, and compare the degree of tissue inflammation with somatic cell counts. Numerous Gram-positive and Gram-negative bacteria were isolated from all samples, majority of which were environmental mastitis pathogens. Histological features referable to chronic mastitis were observed in 92% udders. Lymphocytes, plasma cells and macrophages were found to evolve into aggregates in 48% udders, which often organized to form tertiary lymphoid structures (TLSs). A predominance of interstitial CD8+ over CD4+ lymphocytes and, in TLSs, scattered CD8+ lymphocytes in the mantle cells and CD79+ lymphocytes in germinal centers, were evidenced. Environmental pathogens are known to persist and cause chronic inflammatory changes in buffaloes, where CD8+ lymphocytes play an important role by controlling the local immune response. Moreover, the TLSs evidenced here for the first time in buffalo mastitis, could play a role in maintaining immune responses against persistent antigens, thereby contributing in determining the chronic course of mastitis.

Classification, bacteriological findings, and analysis of sex hormone receptors and cytokine expression in mammary lesions of abattoir sows

Mammary lesions in sows can prevent suckling piglets from consuming colostrum that provides fundamental nutrients and protective immunity. Although mammary gross lesions are frequently found in sows at farms or slaughterhouses, with the exception of mastitis, they have received little research attention. In this study, we investigated mammary lesions observed in South Korean sows between 2015 and 2016. Mammary tissue samples of 82 sows showing gross lesions during meat inspection were histologically classified and immunohistochemical analysis was conducted to assess the expression of estrogen receptor (ER)-α, ER-β, and progesterone receptor (PR) for mammary hyperplastic lesions as well as that of cluster of differentiation (CD) 3, CD79a, interleukin (IL)-1α, IL-1β, IL-6, and IL-8 for mastitis. Furthermore, 20 swab samples were cultured, and the isolated bacteria were identified using polymerase chain reactions for 16S ribosomal RNA genes. The lesions were classified as hyperplasia, mastitis, or hyperplasia with mastitis. Immunohistochemistry results revealed that there was neither expression of ER-α nor of ER-β, but all examined hyperplastic samples expressed PR. In addition, there was a significant correlation between CD3 and IL-1β expressions, as well as between IL-1β and IL-6 expressions. Regarding the identity of the isolated bacteria, Pseudomonas spp. were most frequently detected. The results of this study have revealed the incidence and characteristics of porcine mammary lesions.

Ectasia ductal mamaria, una entidad poco frecuente en la edad pediátrica: A propósito de un caso / Duct ectasia, an infrequent condition in childhood: A case report

La secreción sanguínea a través del pezón (telorragia) es un síntoma muy poco frecuente y que genera gran alarma en pediatría por su relación con el carcinoma en la edad adulta. La entidad más frecuente asociada en edades tempranas, de naturaleza benigna y autolimitada, es la ectasia ductal mamaria. Se caracteriza por la dilatación del conducto mamario, fibrosis e inflamación periductal. La etiología es desconocida y multifactorial. Son pocos casos los descritos en la literatura científica. Se presenta a un lactante de 5 meses con telerragia por ectasia ductal mamaria, cuya resolución fue espontánea a las 4 semanas. Nuestro objetivo es facilitar el rápido reconocimiento por parte de los médicos, dar a conocer esta patología tan poco frecuente y, así, evitar estudios y tratamientos agresivos e invasivos innecesarios.

Bloody discharge from the nipple (thelorrhagia) is a rare symptom in childhood and is a cause of great concern due to the association with carcinoma in adults. The most common cause in children is mammary duct ectasia, which is a benign and self-limiting condition. It is characterized by dilatation of the mammary ducts, fibrosis and periductal inflammation. The etiology has not been identified and is multifactorial. Up to date, only isolated case reports have been published. Therefore, we present a review of the literature and we report a case of a fivemonth- old male infant that resolves spontaneously. We aimed to improve physicians’ diagnosis accuracy, the knowledge of this condition and to avoid aggressive studies and treatments.

Mama tuberosa: clasificación y alternativas quirúrgicas en los últimos años / Tuberous breast: classification and surgical alternatives in the last years

La mama tuberosa constituye una anomalía congénita de la mama que afecta a mujeres jóvenes unilateral o bilateralmente, manifestándose en la pubertad con el crecimiento de la mama y presentando un impacto psicológico significativo en las pacientes. Se caracteriza por una deficiencia en las dimensiones horizontal y vertical de la mama, constricción de la base mamaria, hipoplasia parenquimatosa, deficiencia de piel del polo inferior, malposición superior del surco submamario, hernia areolar y asimetría. Debido a la gran variedad de formas de presentación, la mama tuberosa ha sido tratada quirúrgicamente con numerosos tipos de técnicas por diferentes cirujanos a lo largo del tiempo. No se ha llegado a un consenso sobre la mejor técnica quirúrgica. Con una correcta clasificación y evaluación preoperatoria adecuada se puede llegar a un planeamiento quirúrgico más acertado.

Tuberous breast is a congenital anomaly of the breast affecting young women unilaterally or bilaterally, manifesting in puberty with the growth of the breast and presenting a significant psychological impact on patients. It is characterized by a deficiency in the horizontal and vertical dimensions of the breast, contricted base,underdevelopment of the breast, skin deficiency of the lower pole, superiorly malpositioned submammary fold, areolar herniation and asymmetry. Due to the great variety of presentation forms, the tuberous breast has been treated surgically with many types of techniques by different surgeons over time. No consensus has been reached on the best surgical technique. With a correct classification, and adequate preoperative evaluation, it is possible to arrive at a more successful surgical planning.

Avances en el conocimiento de las proteínas de la leche materna / Advances in the knowledge about human milk proteins

La glándula mamaria y la leche materna son el resultado de millones de años de una evolución que llevó a una composición óptima para el crecimiento y desarrollo de recién nacidos y lactantes; la leche materna favorece el crecimiento, la adaptación y la supervivencia de su organismo y de sus órganos inmaduros. Análisis recientes han demostrado en ella la presencia de 1606 proteínas que en su mayoría son sintetizadas en los acinos de la glándula mamaria aunque otras proteínas y péptidos provienen de órganos como el sistema linfático y el aparato digestivo. La composición de la leche materna incluye enzimas que modifican sus proteínas y originan péptidos antimicrobianos, antihipertensivos y estimuladores del metabolismo. Esta actividad proteolítica actúa en sitios específicos de las cadenas peptídicas de la proteína de la leche. La activación extemporánea de estos enzimas en los acinos es regulada por péptidos inhibidores y activadores que previenen procesos inflamatorios. Algunos enzimas de la leche actúan en el tubo digestivo de recién nacidos y lactantes y complemen tan la menor concentración y actividad de sus propios enzimas digestivos. Así, la enteroquinasa de la leche estimula la liberación de enzimas pancreáticos (mediada por el estímulo de la colecistoquinina-pancreozimina); la lipasa activada por las sales biliares complementa la baja producción de lipasa pancreática. Estas actividades probablemente facilitan la nutrición de los prematuros, cuyo tubo di gestivo es más permeable a las proteínas parcialmente hidrolizadas y cuyas actividades enzimáticas y factores defensivos locales no han alcanzado su plena madurez. Esto también puede estimular en ellos la tolerancia inmunológica. En este artículo se presentan los aspectos fisiológicos relevantes de la leche materna, y los avances en el conocimiento de su composición, para el cabal conocimiento del pediatra de esta importante materia.

The mammary gland and maternal milk are the product of millions of years of evolution that resul ted in an optimal composition that sustains the growth and development of newborns and infants. Maternal milk supports the growth, adaptation and survival of this immature organism. Recent studies have detected 1606 different proteins in human milk, most of them synthesized in the acini of the glandular tissue while others originate from distant organs such as the lymphoid tissue and the digestive tract. Maternal milk enzymes modify its proteins and liberate peptides with antimicrobial, antihypertensive or stimulatory activities. This proteolytic activity occurs at specific sites in peptide chains. To prevent the extemporaneous activation of these proteolytic enzymes, that would result in inflammatory processes, maternal milk also contains inhibitory peptides that together with the stimulatory peptides conform a complex regulatory system. Some enzymes in maternal milk main tain their activity in the gastrointestinal tract of infants and compensate for the decreased activity of digestive tract enzymes in newborns. Thus, the milk enterokynase stimulates the release of pancreatic proteases as it induces the liberation of cholecystokynin/pancreozymin. The bile salt-activated lipase of human milk is activated in the duodenum by the infants' bile salts and partially compensates for the low levels of pancreatic lipase in newborns. These milk enzymes probably contribute to the nutrition of premature infants as they increase the availability of amino acids and peptides in their upper gastrointestinal tract; furthermore, as their intestinal epithelium is more permeable to peptides and partially digested protein this may help induce immune tolerance. The most relevant issues in the physiology and composition of the maternal milk are presented in this review.

Significance of Vesicle-Associated Membrane Protein 8 Expression in Predicting Survival in Breast Cancer / 한국유방암학회지

PURPOSE: Vesicle-associated membrane protein 8 (VAMP8) is a soluble N-ethylmaleimide-sensitive factor receptor protein that participates in autophagy by directly regulating autophagosome membrane fusion and has been reported to be involved in tumor progression. Nevertheless, the expression and prognostic value of VAMP8 in breast cancer (BC) remain unknown. This study aimed to evaluate the clinical significance and biological function of VAMP8 in BC. METHODS: A total of 112 BC samples and 30 normal mammary gland samples were collected. The expression of VAMP8 was assessed in both BC tissues and normal mammary gland tissues via a two-step immunohistochemical detection method. RESULTS: The expression of VAMP8 in BC tissues was significantly higher than that in normal breast tissues. Furthermore, increased VAMP8 expression was significantly correlated with tumor size (p=0.007), lymph node metastasis (p=0.024) and recurrence (p=0.001). Patients with high VAMP8 expression had significantly lower cumulative recurrence-free survival and overall survival (p < 0.001 for both) than patients with low VAMP8 expression. In multivariate logistic regression and Cox regression analyses, lymph node metastasis and VAMP8 expression were independent prognostic factors for BC. CONCLUSION: VAMP8 is significantly upregulated in human BC tissues and can thus be a practical and potentially effective surrogate marker for survival in BC patients.

A simple calculation for the preoperative estimation of transverse rectus abdominis myocutaneous free flap volume in 2-stage breast reconstruction using a tissue expander

BACKGROUND: Flap volume is an important factor for obtaining satisfactory symmetry in breast reconstruction with a transverse rectus abdominis myocutaneous (TRAM) free flap. We aimed to develop an easy and simple method to estimate flap volume. METHODS: We performed a preoperative estimation of the TRAM flap volume in five patients with breast cancer who underwent 2-stage breast reconstruction following an immediate tissue expander operation after a simple mastectomy. We measured the height and width of each flap zone using a ruler and measured the tissue thickness by ultrasound. The volume of each zone, approximated as a triangular or square prism, was then calculated. The zone volumes were summed to obtain the total calculated volume of the TRAM flap. We then determined the width of zone II, so that the calculated flap volume was equal to the required flap volume (1.2×1.05×the weight of the resected mastectomy tissue). The TRAM flap was transferred vertically so that zone III was located on the upper side, and zone II was trimmed in the sitting position after vascular anastomosis. We compared the estimated flap width of zone II (=X) with the actual flap width of zone II. RESULTS: X was similar to the actual measured width. Accurate volume replacement with the TRAM flap resulted in good symmetry in all cases. CONCLUSIONS: The volume of a free TRAM flap can be straightforwardly estimated preoperatively using the method presented here, with ultrasound, ruler, and simple calculations, and this technique may help reduced the time required for precise flap tailoring.

Cáncer de mama en hombre: Presentación de caso / Male Breast Cancer: Case Report

El cáncer de mama en hombres es poco frecuente, representa menos del 1 % de todos los cánceres masculinos, se presenta entre los 60-70 años con un pico de edad de 67 años; el carcinoma ductal invasivo es el que prevalece en varones, clínicamente se detecta como un nódulo unilateral indoloro retroareolar, o paraareolar. A diferencia de la mujer donde se realizan estudios de tamizaje, en los hombres suele diagnosticarse más tarde, porque buscan atención médica tardíamente por la poca incidencia de cáncer en pacientes masculinos, por la ausencia de signos y síntomas tempranos. Actualmente se puede utilizar para el diagnóstico la mamografía que ayuda a diferenciar entre enfermedades mamarias benignas y malignas. En este artículo se presenta el caso clínico de un paciente que acude al Instituto Hondureño de Seguridad Social, a quien se le diagnosticó carcinoma ductal.

Breast cancer in men is rare, it represents less then 1% of all male cancers, it's present between the ages of 60 through 70 years with an age peak at 67 years; the invasive ductal carcinoma is the most prevalent in men. Clinically, it is detected as an odorless, unilateral retro- or paraareolar nodule. Unlike with women, where screening studies are performed, in men it's usually diagnosed later on, because the low incidence of this cancer in male patients and the absence of early signs and symptoms leads to a delayed search for medical attention delayed. For diagnosis, a mammography can be used that helps differentiate between benign and malign mammary diseases. In this article we presented the clinical case of a patient that visits the Honduran Social Security Institute, diagnosed with ductal carcinoma.

Ectopic Male Breast Cancer in the Perineum: A Case Report / 한국유방암학회지

Ectopic breast tissue and male breast cancer are both very rare diseases with only a few reports in the literature. Here, we present the first case of ectopic male breast cancer in the perineum. The patient was a 70-year-old man with a palpable mass in the perineum. A wide local excision and inguinal lymph node dissection revealed invasive breast carcinoma of no special type involving the skin and subcutis, and inguinal lymph node metastases. Immunohistochemical staining showed that the tumor cells were strongly positive for estrogen and progesterone receptors and negative for human epidermal growth factor receptor 2. Moreover, no p53 overexpression was observed. Herein, the clinical and pathologic features, as well as a review of ectopic male breast cancer are discussed.

Low-Dose Bisphenol A Increases Bile Duct Proliferation in Juvenile Rats: A Possible Evidence for Risk of Liver Cancer in the Exposed Population?

Increasing concern is being given to the association between risk of cancer and exposure to low-dose bisphenol A (BPA), especially in young-aged population. In this study, we investigated the effects of repeated oral treatment of low to high dose BPA in juvenile Sprague-Dawley rats. Exposing juvenile rats to BPA (0, 0.5, 5, 50, and 250 mg/kg oral gavage) from post-natal day 9 for 90 days resulted in higher food intakes and increased body weights in biphasic dose-effect relationship. Male mammary glands were atrophied at high dose, which coincided with sexual pre-maturation of females. Notably, proliferative changes with altered cell foci and focal inflammation were observed around bile ducts in the liver of all BPA-dosed groups in males, which achieved statistical significance from 0.5 mg/kg (ANOVA, Dunnett’s test, p<0.05). Toxicokinetic analysis revealed that systemic exposure to BPA was greater at early age (e.g., 210-fold in C(max), and 26-fold in AUC at 50 mg/kg in male on day 1 over day 90) and in females (e.g., 4-fold in C(max) and 1.6-fold in AUC at 50 mg/kg vs. male on day 1), which might have stemmed from either age- or gender-dependent differences in metabolic capacity. These results may serve as evidence for the association between risk of cancer and exposure to low-dose BPA, especially in young children, as well as for varying toxicity of xenobiotics in different age and gender groups.

Genotypic Identification of Cystoisospora in Immunocompromised Patients Using T(m)-Variation Analysis

Cystoisospora is responsible for morbidity in immunocompromised patients. PCR is sensitive for diagnosing Cystoisospora; however, it needs reevaluation for differential molecular diagnosis of cystoisosporiasis. We aimed at evaluating melting curve analysis (MCA) after real-time PCR (qPCR) in diagnosis and genotyping of Cystoisospora as an alternative to conventional PCR. We included 293 diarrheic stool samples of patients attending the Department of Clinical Oncology and Nuclear Medicine of Cairo University Hospitals, Egypt. Samples were subjected to microscopy, nested PCR (nPCR), and qPCR targeting the internal transcribed spacer 2 region (ITS2) of the ribosomal RNA (r RNA) gene followed by melting temperatures (T(m)s) analysis and comparing the results to PCR-RFLP banding patterns. Using microscopy and ITS2-nPCR, 3.1% and 5.8% of cases were Cystoisospora positive, respectively, while 10.9% were positive using qPCR. Genotyping of Cystoisospora by qPCR-MCA revealed 2 genotypes. These genotypes matched with 2 distinct melting peaks with specified T(m)s at 85.8°C and 88.6°C, which indicated genetic variation among Cystoisospora isolates in Egypt. Genotype II proved to be more prevalent (65.6%). HIV-related Kaposi sarcoma and leukemic patients harbored both genotypes with a tendency to genotype II. Genotype I was more prevalent in lymphomas and mammary gland tumors while colorectal and hepatocellular tumors harbored genotype II suggesting that this genotype might be responsible for the development of cystoisosporiasis in immunocompromised patients. Direct reliable identification and differentiation of Cystoisospora species could be established using qPCR-T(m)s analysis which is useful for rapid detection and screening of Cystoisospora genotypes principally in high risk groups.