Neoplasms, Glandular and Epithelial

肿瘤,腺体和上皮
  • 文章类型: Case Reports
    具有胸腺样元件的梭形上皮肿瘤(SETTLE)是一种罕见的甲状腺恶性肿瘤,据信起源于甲状腺内胸腺组织。它主要影响出现不同持续时间的甲状腺肿块的年轻人和儿童,在成人中很少发生。它具有高的总生存率,并有延迟转移的趋势。SETTLE是一种双相分叶状肿瘤,由梭形细胞和组织病理学检查可见的腺体形成组成。尽管其典型的形态,但由于其稀有性和与其他接近的模拟物(如癌)重叠的形态,通常在组织病理学上被误诊。滑膜肉瘤和胸腺瘤。在此,我们报告了一例发生在颈部肿块的中年女性中的病例。鉴于CK的共同表达,她最初诊断为转移性低分化鳞状细胞癌,可能患有口喉原发性癌,p40和p16的免疫组织化学。患者接受了改良颈清扫术的手术切除。在我们医院的检查中,它被诊断为SETTLE,并且在1年的随访期后她仍然没有疾病。勤奋的组织病理学检查与明智的IHC标记物结合临床放射学检查是诊断的主要依据。到目前为止,在文献中尚未记录或评估弥漫性和强p16免疫表达,并需要探索其在这个罕见实体中的诊断效用。
    Spindle epithelial tumor with thymus-like elements (SETTLE) is a rare malignant neoplasm of the thyroid gland which is believed to arise from intrathyroidal thymic tissue. It predominantly affects young adults and children presenting with a thyroid mass of variable duration and rarely occurs in adults. It has a high overall survival with a tendency for delayed metastasis. SETTLE is a biphasic lobulated tumor composed of spindle shaped cells along with glandular formations seen on histopathological examination. Despite its typical morphology it is commonly misdiagnosed on histopathology due to its rarity and overlapping morphology with other close mimics such as a carcinoma, synovial sarcoma and thymoma. Herein we report such a case occurring in a middle aged female presenting with a neck mass. She had an initial diagnosis of metastatic poorly differentiated squamous cell carcinoma possibly with an orophayngeal primary in view of co expression of CK, p40 and p16 on immunohistochemistry. The patient underwent surgical resection with modified neck dissection. On review at our hospital it was diagnosed as SETTLE and she remains disease free after a follow-up period of 1 year. Diligent histopathological examination espoused with a judicious panel of IHC markers in conjunction with clinicoradiological findings forms the mainstay of diagnosis. Diffuse and strong p16 immunoexpression has not been documented or evaluated in literature so far, and needs to be explored for its diagnostic utility in this rare entity.
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  • 文章类型: Journal Article
    编辑注意。-RadioGraphics更新文章补充或更新以前在RadioGraphics中发布的完整文章中的信息。这些更新,由上一篇文章的至少一位作者撰写,提供一个简短的概要,强调重要的新信息,如技术进步,修订的成像协议,涉及影像学的新临床指南,或更新的分类方案。
    Editor\'s Note.-RadioGraphics Update articles supplement or update information found in full-length articles previously published in RadioGraphics. These updates, written by at least one author of the previous article, provide a brief synopsis that emphasizes important new information such as technological advances, revised imaging protocols, new clinical guidelines involving imaging, or updated classification schemes.
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  • 文章类型: Journal Article
    许多癌症转移到胸膜,导致引起呼吸困难和不适的积液。不管是什么组织的起源,胸膜恶性肿瘤是侵袭性的,并且是致命的,没有延长寿命的治疗方法。胸膜间皮单层通过紧密连接连接,形成包含的生物反应器状空间,浓缩由间皮分泌的细胞因子和趋化因子,肿瘤,和浸润免疫细胞。这个空间代表了一个深刻地影响肿瘤和免疫细胞行为的独特环境。定义胸膜分泌体是合理开发局部胸膜内免疫治疗的重要步骤。
    我们使用40分析物面板和Luminex多路复用技术,在多种癌症中测量了252个恶性胸腔积液(MPE)样品的细胞因子/趋化因子含量。
    十一种分析物始终以≥10.0pM的浓度存在:CXCL10/IP10(几何平均值=672.3pM),CCL2/MCP1(562.9pM),sIL-6Rα(403.1pM),IL-6(137.6pM),CXCL1/GRO(80.3pM),TGFβ1(76.8pM),CCL22/MDC(54.8pM),CXCL8/IL-8(29.2pM),CCL11/Eotaxin(12.6pM),IL-10(11.3pM),和G-CSF(11.0pM)。都能够介导趋化性,促进上皮向间充质转化,或者免疫抑制,据报道,许多是由细胞因子IL-6及其可溶性受体介导的促炎细胞因子级联的下游。
    数据表明,在转移到胸膜的上皮癌中,几种细胞因子和趋化因子的浓度很高,并支持了以下观点:胸膜环境是导致MPE临床过程的主要因素。sIL-6Rα与IL-6摩尔比为2.7,确保几乎所有上皮,胸膜环境中的免疫和血管内皮细胞受到IL-6信号的影响。IL-6在MPE的发病机理中可能发挥的核心作用支持靶向IL-6/IL-6R轴的治疗方法。
    UNASSIGNED: Many cancers metastasize to the pleura, resulting in effusions that cause dyspnea and discomfort. Regardless of the tissue of origin, pleural malignancies are aggressive and uniformly fatal, with no treatment shown to prolong life. The pleural mesothelial monolayer is joined by tight junctions forming a contained bioreactor-like space, concentrating cytokines and chemokines secreted by the mesothelium, tumor, and infiltrating immune cells. This space represents a unique environment that profoundly influences tumor and immune cell behavior. Defining the pleural secretome is an important step in the rational development localized intrapleural immunotherapy.
    UNASSIGNED: We measured cytokine/chemokine content of 252 malignant pleural effusion (MPE) samples across multiple cancers using a 40-analyte panel and Luminex multiplexing technology.
    UNASSIGNED: Eleven analytes were consistently present in concentrations ≥ 10.0 pM: CXCL10/IP10 (geometric mean = 672.3 pM), CCL2/MCP1 (562.9 pM), sIL-6Rα (403.1 pM), IL-6 (137.6 pM), CXCL1/GRO (80.3 pM), TGFβ1 (76.8 pM), CCL22/MDC (54.8 pM), CXCL8/IL-8 (29.2 pM), CCL11/Eotaxin (12.6 pM), IL-10 (11.3 pM), and G-CSF (11.0 pM). All are capable of mediating chemotaxis, promotion of epithelial to mesenchymal transition, or immunosuppression, and many of are reportedly downstream of a pro-inflammatory cytokine cascade mediated by cytokine IL-6 and its soluble receptor.
    UNASSIGNED: The data indicate high concentrations of several cytokines and chemokines across epithelial cancers metastatic to the pleura and support the contention that the pleural environment is the major factor responsible for the clinical course of MPE across cancer types. A sIL-6Rα to IL-6 molar ratio of 2.7 ensures that virtually all epithelial, immune and vascular endothelial cells in the pleural environment are affected by IL-6 signaling. The central role likely played by IL-6 in the pathogenesis of MPE argues in favor of a therapeutic approach targeting the IL-6/IL-6R axis.
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  • 文章类型: Case Reports
    胸腺上皮肿瘤是罕见的恶性肿瘤,每年每百万人中有1.7例发病率。由于它们与自身免疫性疾病的关联,它们构成了重大的管理挑战。在这个案例报告中,我们介绍了一名诊断为晚期B2/B3胸腺瘤和Good\'s综合征的患者的21年病史。患者在仅接受两个周期的免疫检查点抑制剂Nivolumab后实现了完全和持久的反应。然而,这种阳性结果伴随着严重的免疫相关性心肌炎的发展,并伴有巨细胞病毒的再激活.此外,该患者出现了高度罕见的胸腺肿瘤的膈下直肠旁播散,这是文献中很少描述的情况。尽管免疫检查点抑制剂成功实现了完整和持久的反应,免疫相关不良事件的出现凸显了与这些治疗相关的潜在挑战,强调需要仔细监测和全面了解癌症之间复杂的相互作用,免疫系统失调和免疫疗法。
    Thymic epithelial tumors are rare malignancies with an incidence of 1.7 cases per million people per year. They pose significant management challenges due to their association with autoimmune disorders. In this case report, we present the 21-year history of a patient diagnosed with advanced B2/B3 thymoma and Good\'s syndrome. The patient achieved a complete and durable response after receiving only two cycles of the immune checkpoint inhibitor Nivolumab. However, this positive outcome was accompanied by the development of severe immune-related myocarditis complicated by reactivation of cytomegalovirus. Moreover, the patient developed a highly uncommon subdiaphragmatic pararectal dissemination of the thymic tumor, which is a condition rarely described in the literature. Despite the success in achieving complete and durable response with immune checkpoint inhibitors, the emergence of immune-related adverse events highlights the potential challenges associated with these treatments, emphasizing the need for careful monitoring and a comprehensive understanding of the intricate interplay between cancer, immune system dysregulations and immunotherapy.
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  • 文章类型: Journal Article
    Introduction and objective: The approach to patients with advanced or metastatic high-grade epithelial ovarian cancer (EOC) has evolved over time with the advent of new therapies and multimodal strategies. The objective of this consensus of experts is to generate national recommendations for the profiling and management of advanced or metastatic high-grade OEC, defined as stages III and IV of the “The International Federation of Gynecology and Obstetrics (FIGO) classification at the time of diagnosis to base on the literature review that included international evidence-based clinical practice guidelines (CPG). Material and methods: Eleven panelists (oncologists and gynecological oncologists) answered 8 questions about the profiling and management of advanced or metastatic ovarian epithelial carcinoma. The panelists were chosen for their academic profile and influence in national health institutions. Guidelines from the “ESMO Standardized Operating Procedures Consensus Conference” were used to develop the consensus. It was agreed that the level of agreement to accept a recommendation should be ≥ 80%. The document was peer reviewed. Results: Eight general recommendations are made, which are presented into five domains. Some of these recommendations are subdivided into specific recommendations. Initial treatment Recommendation 1.1 Complete primary cytoreduction (PCS) surgery is suggested as the initial therapy of choice for patients with high-grade or metastatic EOC, which should ideally be carried out in centers with experience, followed by adjuvant therapy. 1.2 Neoadjuvant chemotherapy followed by interval cytoreduction surgery (ICS) is suggested in those who are unlikely to achieve a complete cytoreduction in PCS either due to unresectable metastatic disease or who present unresectability criteria (imaging, laparoscopic and/or by laparotomy) and that have been defined by a gynecological oncologist and patients with poor functional status and comorbidities according to the criteria of the multidisciplinary team (clinical oncology, gynecological oncology, radiology, etc.). Recommendation 2. In patients with high-grade epithelial ovarian cancer (EOC), in stage III locally advanced or metastatic, who received neoadjuvant chemotherapy and achieved a complete or partial response (cytoreduction with tumor residue < 2.5 mm), the use of Hyperthermic IntraPeritoneal Chemotherapy (HIPEC) could be considered as an alternative to standard platinum-based adjuvant intravenous chemotherapy during interval cytoreductive surgery, after discussion in a multidisciplinary tumor board, at a center experienced in treating this type of patients. Use of genetic testing. Recommendation 3. It is suggested at the time of diagnosis to offer molecular genetic testing to all patients with high-grade advanced or metastatic EOC regardless of family history. Recommendation 4. It is suggested to offer genetic counseling, by qualified personnel, to all patients with high-grade advanced or metastatic EOC who are ordered genetic testing. Recommendation 5. It is suggested that all patients with advanced or metastatic high-grade EOC undergo a germ panel that includes the Breast Cancer Susceptibility Genes 1/2 genes (BRCA 1/2) and the other susceptibility genes according to with institutional protocols and the availability of genetic testing panels; If it is negative, then somatic testing should be performed that includes the homologous recombination deficiency (HRD) status, regardless of family history. Adjuvant Therapy Recommendation 6. 6.1. It is suggested that all patients with advanced stage III/IV EOC, with PSC of (0-2), got adjuvant intravenous chemotherapy as standard treatment within six weeks after Prc. It is suggested paclitaxel/carboplatin. Recommendation 6.2. It is suggested to use standard chemotherapy base on platinum plus Bevacizumab as adjuvant chemotherapy to patients with high-risk disease (EOC stage IV or stage III with suboptimal tumor cytoreduction), following by bevacizumab as maintenance. The use of bevacizumab as maintenance therapy is not recommended if bevacizumab was not included in the first line of treatment. We suggested the dose used in GOG-0218 and ICON7 trials. Recommendation 6.3 It is suggested combined intravenous/intraperitoneal chemotherapy only for selected patients, with optimal cytoreduction (residual lesions < 1 cm), especially those without residual disease (R0) and who are evaluated in a multidisciplinary meeting. It is not considered standard treatment. Recommendation 6.4. 6.4.1 It is suggested to use Poly ADP ribose polymerase (PARP) inhibitors such as olaparib or niraparib as maintenance after receiving first-line chemotherapy in patients with stage III/IV BRCA1/2 positive EOC who received platinumbased chemotherapy and obtained complete response/partial response (CR/PR), 6.4.2 It is suggested to use olaparib alone or in combination with bevacizumab or niraparib in patients with stage III/IV BRCA1/2 positive EOC who received platinum-based chemotherapy plus bevacizumab and achieved CR/PR. 6.4.3 It is suggested to use niraparibin patients with stage III/IV BRCA1/2 negative or unknown EOC who received platinum-based chemotherapy and achieved CR/PR. 6.4.4 It is suggested to use bevacizumab or olaparib plus bevacizumab in patients with EOC stage III/IV BRCA1/2 negative or unknown (HRD positive) who received platinum-based chemotherapy plus bevacizumab and obtained CR/PR. Treatment of disease relapse Recommendation 7. Secondary cytoreductive surgery followed by chemotherapy is suggested for selected patients with high-grade advanced EOC in first relapse, platinum-sensitive (platinum-free interval ≥ 6 months), positive “Arbeitsgemeinschaft Gynäkologische Onkologie – AGO” score or “I-model” positive (< 4.7) with a potential resection to R0 in centers with access to optimal surgical and postoperative support. Note: Platinum-free interval and AGO score have only been developed as positive predictors of complete resection and not to exclude patients from surgery. Recommendation 8. 8.1 For patients with relapse advanced high-grade EOC platinum-sensitive, the following is suggested: Platinum-based combination chemotherapy: carboplatin/liposomal doxorubicin or carboplatin/paclitaxel or carboplatin/nab-paclitaxel or carboplatin/docetaxel or carboplatin/gemcitabine) for six cycles. If combination therapy is not tolerated, give carboplatin or cisplatin alone. Combination chemotherapy (carboplatin/gemcitabine or carboplatin/paclitaxel or carboplatin/doxorubicin liposomal) plus bevacizumab followed by bevacizumab as maintenance (until progression or toxicity). Recommendation 8.2 For patients with relapsed advanced high-grade EOC platinum-resistant, it is suggested: Sequential treatment with chemotherapy, preferably with a non-platinum single agent (weekly paclitaxel or pegylated liposomal doxorubicin or docetaxel or oral etoposide or gemcitabine or trabectidine or, topotecan). Weekly paclitaxel or pegylated liposomal doxorubicin or topotecan could be administrate with or without bevacizumab. Other agents are considered potentially active (capecitabine, cyclophosphamide, ifosfamide, irinotecan, oxaliplatin, pemetrexed, vinorelbine, cyclophosphamide) could be recommended for later lines. Hormone receptor-positive patients who do not tolerate or have no response to cytotoxic regimens may receive hormone therapy with tamoxifen or other agents, including aromatase inhibitors (anastrozole and letrozole) or leuprolide acetate, or megestrol acetate. Patients with a performance score ≥ 3 should be considered only for best supportive care. Recommendation 8.3 Maintenance therapy with PARP inhibitors: It is suggested in patients with relapse advanced high-grade EOC stage III/IV BRCA1/2 (positive, negative or unknown) who have received two or more lines of platinum-based chemotherapy and have achieved CR/PR, use olaparib, niraparib or rucaparib. Niraparib could be useful in BRCA 1/2 +/-/unknown patients, as rucaparib, however, the latter does not yet have approval from the regulatory office in Colombia. Conclusions: It is expected that the recommendations issued in this consensus will contribute to improving clinical care, oncological impact, and quality of life of these women.
    Introducción y objetivo: el abordaje de pacientes con cáncer epitelial de ovario (CEO) de alto grado avanzado o metastásico ha ido evolucionando a través del tiempo con el advenimiento de nuevas terapias y estrategias multimodales. El objetivo de este consenso de expertos es generar recomendaciones nacionales para el perfilamiento y manejo del CEO de alto grado avanzado o metastásico, definido como estadios III y IV de la clasificación de la Federación Internacional de Ginecología y Obstetricia (FIGO) al momento del diagnóstico, a partir de la revisión de la literatura que incluyó guías de práctica clínica (GPC) internacionales basadas en la evidencia. Materiales y métodos: once panelistas (oncólogos y ginecólogos oncólogos) respondieron ocho preguntas sobre el perfilamiento y manejo del carcinoma epitelial de ovario avanzado o metastásico. Los panelistas fueron escogidos por su perfil académico e influencia en instituciones de salud nacionales. Para el desarrollo del consenso se utilizaron los lineamientos de la “Conferencia de consenso de procedimientos operativos estandarizados de ESMO”. Se definió que el nivel de acuerdo para aceptar una recomendación debía ser ≥ 80%. El documento fue revisado por pares. Resultados: Se hacen 8 recomendaciones generales, presentadas en cinco dominios; algunas de ellas se subdividen en recomendaciones específicas. Tratamiento inicial Recomendación 1 1.1. Como terapia inicial de elección para pacientes con CEO de alto grado o metastásico se sugiere la cirugía de citorreducción primaria (Cpr) completa que, idealmente, debe realizarse en centros con experiencia, seguida de terapia adyuvante. 1.2. Se sugiere quimioterapia neoadyuvante seguida de cirugía de citorreducción de intervalo (Cint) en quienes sea improbable alcanzar una citorreducción completa en la Cpr, bien sea por enfermedad metastásica no resecable o que presenten criterios de irresecabilidad (imagenológicos, laparoscópicos o por laparotomía) que hayan sido definidos por un ginecólogo oncólogo. También en pacientes con un pobre estado funcional y comorbilidades de acuerdo con el criterio del equipo multidisciplinario (oncología clínica, ginecología oncológica, radiología, etc.). Recomendación 2. En pacientes con CEO de alto grado, en estadio III localmente avanzado o metastásico, que recibieron quimioterapia neoadyuvante y alcanzaron respuesta completa o parcial (citorreducción con residuo tumoral < 2,5 mm), se podría evaluar el uso de la quimioterapia intraperitoneal hipertérmica (Hyperthermic IntraPeritoneal Chemotherapy - HIPEC) como alternativa a la quimioterapia IV adyuvante estándar basada en platinos durante la Cint, previa discusión en junta multidisciplinaria, en un centro de experiencia en este tipo de pacientes. Uso de pruebas genéticas Recomendación 3. Al momento del diagnóstico, se sugiere ofrecer testeo molecular genético a toda paciente con CEO de alto grado avanzado o metastásico, independientemente de la historia familiar. Recomendación 4. Se sugiere ofrecer asesoramiento genético, por parte de personal calificado, a toda paciente con CEO de alto grado avanzado o metastásico a quien se le ordene un testeo genético. Recomendación 5. Se sugiere que a toda paciente con CEO de alto grado avanzado o metastásico se le realice panel germinal que incluya los genes de susceptibilidad al cáncer de mama 1/2 (BRCA 1/2) y los otros genes de susceptibilidad de acuerdo con los protocolos institucionales y la disponibilidad de paneles de testeo genético; si es negativo entonces se debería realizar testeo somático que incluya el estatus de deficiencia de la recombinación homóloga (homologous recombination deficiency - HRD), independientemente de la historia familiar. Terapia adyuvante Recomendación 6 6.1. Se sugiere que a toda paciente con CEO estadios III/IV avanzado o metastásico, con estatus de desempeño (performance score care - PSC) de 0-2 se le administre como tratamiento estándar quimioterapia intravenosa (IV) adyuvante dentro de las seis semanas posteriores a la Cpr. Se sugiere administrar paclitaxel/carboplatino. 6.2. Se sugiere utilizar quimioterapia estándar basada en platino más bevacizumab como adyuvancia en pacientes con enfermedad de alto riesgo (CEO estadios IV o III con citorreducción tumoral subóptima), continuando con bevacizumab como mantenimiento. No se recomienda el uso de bevacizumab como terapia de mantenimiento si no se incluyó en la primera línea de tratamiento. Se sugiere seguir los esquemas de los estudios Gynecologic Oncology Group Study (GOG-0218) e International Collaborative Ovarian Neoplasm (ICON7). 6.3. Se sugiere la quimioterapia combinada IV/intraperitoneal (IP) solo para pacientes seleccionadas, con una citorreducción óptima (lesiones residuales < 1 cm), en especial aquellas sin enfermedad residual (R0) y que sean evaluadas en junta multidisciplinaria. La quimioterapia combinada IV/IP no se considera como tratamiento estándar. 6.4. 6.4.1. Se sugiere utilizar inhibidores de poli(ADP-ribosa) polimerasa (PARP) tales como olaparib o niraparib como mantenimiento después de recibir una primera línea de quimioterapia en pacientes con CEO estadios III/IV BRCA1/2 positivo que recibieron quimioterapia basada en platino y obtuvieron respuesta completa/respuesta parcial (RC/RP). 6.4.2. Se sugiere utilizar olaparib solo o en combinación con bevacizumab o niraparib en pacientes con CEO estadios III/IV BRCA1/2 positivo que recibieron quimioterapia basada en platino más bevacizumab y obtuvieron RC/RP. 6.4.3. Se sugiere utilizar niraparib en pacientes con CEO estadio III/IV BRCA1/2 negativo o desconocido que recibieron quimioterapia basada en platino y obtuvieron RC/RP. 6.4.4. Se sugiere utilizar bevacizumab u olaparib más bevacizumab en pacientes con CEO estadios III/IV BRCA1/2 negativo o desconocido (HRD positivo) que recibieron quimioterapia basada en platino más bevacizumab y obtuvieron RC/RP. Tratamiento de la recaída de la enfermedad Recomendación 7. Se sugiere la realización de la cirugía de citorreducción secundaria (Csec), seguida de quimioterapia, a pacientes seleccionadas con CEO de alto grado avanzado o metastásico en primera recaída, platino-sensibles (intervalo libre de platinos ≥ 6 meses), puntuación Arbeitsgemeinschaft Gynäkologische Onkologie (AGO) positiva o Integrate model (I-Model) positivo (< 4,7), y con una potencial resección a R0, en centros con acceso a soporte quirúrgico y posoperatorio óptimo. Nota: el intervalo libre de tratamiento con platinos y la puntuación AGO solo se han desarrollado como predictores positivos de resección completa y no para excluir a las pacientes de la cirugía. Recomendación 8 8.1. Para pacientes con CEO de alto grado avanzado o metastásico en recaída platino-sensibles se sugiere: Quimioterapia combinada basada en platino: carboplatino/doxorrubicina liposomal o carboplatino/paclitaxel o carboplatino/ nab-paclitaxel o carboplatino/docetaxel o carboplatino/gemcitabina, por seis ciclos. Si no se tolera la terapia combinada, dar carboplatino o cisplatino solo. Quimioterapia combinada: carboplatino/gemcitabina o carboplatino/paclitaxel o carboplatino/doxorubicina liposomal, más bevacizumab, seguida de bevacizumab como mantenimiento (hasta progresión o toxicidad). 8.2. Para pacientes con CEO de alto grado avanzado o metastásico en recaída, platino-resistentes, se sugiere: Tratamiento secuencial con quimioterapia, preferiblemente con un agente único que no sea un platino (paclitaxel semanal o doxorrubicina liposomal pegilada o docetaxel o etopósido oral o gemcitabina o trabectidina o topotecan). El paclitaxel semanal o la doxorrubicina liposomal pegilada o el topotecan pueden ser administrados con o sin bevacizumab. Existen otros agentes que se consideran potencialmente act ivos (capecitabina, ciclofosfamida, ifosfamida, irinotecán, oxaliplatino, pemetrexed, vinorelbina, ciclofosfamida), que se podrían recomendar para líneas posteriores. Las pacientes con receptores hormonales positivos que no toleran o no tienen respuesta a los regímenes citotóxicos pueden recibir terapia hormonal con tamoxifeno u otros agentes, incluidos los inhibidores de la aromatasa (anastrozol y letrozol) o acetato de leuprolide o acetato de megestrol. Pacientes con PSC ≥ 3 deberían ser consideradas solo para el mejor cuidado de soporte. 8.3. Terapia de mantenimiento con inhibidores PARP. Para pacientes con CEO de alto grado avanzado o metastásico en recaída estadios III/IV BRCA1/2 (positivo, negativo o desconocido), que hayan recibido dos o más líneas de quimioterapia basada en platino y hayan alcanzado RC/RP, se sugiere utilizar olaparib, niraparib o rucaparib. El niraparib podría ser útil en pacientes BRCA 1/2 +/-/desconocido, al igual que el rucaparib, sin embargo, este último no tiene aún aprobación del ente regulador en Colombia. Conclusiones: se espera que las recomendaciones emitidas en este consenso contribuyan a mejorar la atención clínica, el impacto oncológico y la calidad de vida de estas mujeres.
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  • 文章类型: Letter
    暂无摘要。
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  • 文章类型: Journal Article
    犬卵巢上皮性肿瘤(OET)目前分为卵巢腺瘤和癌,进一步不一致地分为乳头状或囊性,而在人类医学中,OET被细分为几个亚型。这项研究旨在建立清晰的形态学特征,从而在良性OET和卵巢癌(OvCas)之间进行更一致的区分,并定义犬OvCas的不同组织病理学模式。分析显示,有丝分裂计数阈值>2是区分OvCas与良性OET的潜在标准。除了卵巢腺瘤,在良性OET中,卵巢交界性肿瘤被引入为一个独特的类别。OvCas表现出五种不同的组织病理学模式,即乳头状,实性与管状分化,微乳头状,囊性和肉瘤。由于某些OvCas在形态上可以与其他卵巢肿瘤重叠,细胞角蛋白7的表达,一种在卵巢上皮中表达的细胞角蛋白,被评估并证明是有帮助的,尽管并非在所有情况下都有表达。此外,我们研究了14-3-3σ和环氧合酶2(COX-2)的表达。根据14-3-3σ的频繁表达式,该标记似乎在犬OET中起作用,因为它在正常犬卵巢中不表达。COX-2的不常见表达表明,它是犬OvCas中潜在治疗靶标的不良候选物。
    Canine ovarian epithelial tumours (OETs) are currently divided into ovarian adenomas and carcinomas, which are further inconsistently subclassified as papillary or cystic, whereas in human medicine, OETs are subdivided into several subtypes. This study aimed to establish clear morphological features enabling more consistent distinction between benign OETs and ovarian carcinomas (OvCas) as well as defining different histopathological patterns of canine OvCas. Analysis revealed a mitotic count threshold of >2 as a potential criterion for differentiating OvCas from benign OETs. Alongside ovarian adenomas, ovarian borderline tumours were introduced as a distinct category among benign OETs. OvCas exhibited five different histopathological patterns, namely papillary, solid with tubular differentiation, micropapillary, cystic and sarcomatous. Since some OvCas can morphologically overlap with other ovarian tumours, the expression of cytokeratin 7, a cytokeratin expressed in ovarian epithelium, was assessed and proved helpful, although it was not expressed in all cases. Furthermore, we investigated the expression of 14-3-3σ and cyclooxygenase 2 (COX-2). Based on the frequent expression of 14-3-3σ, this marker appears to have a role in canine OETs since it is not expressed in normal canine ovaries. The infrequent expression of COX-2 suggests that it is a poor candidate as a potential therapeutic target in canine OvCas.
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  • 文章类型: Journal Article
    上皮性卵巢癌(EOC)总体生存率较低,主要是由于频繁复发和对铂类化疗产生耐药性。具有同源重组(HR)缺陷的EOC对基于铂的化疗的敏感性增加,因为铂诱导的DNA损伤无法修复。HR途径中涉及的基因的突变被认为与对治疗的有利反应密切相关。具有这些突变的患者具有更好的预后和提高的存活率。另一方面,EOC中非HR基因突变与化疗耐药增加和预后较差相关.出于这个原因,对治疗和总生存率的准确预测仍然具有挑战性.因此,我们在NCI的癌症基因组图谱(TCGA)程序上分析了360例EOC病例,以鉴定与总生存期密切相关的新基因突变特征.我们发现相当一部分EOC病例在一组31个基因中表现出多个重叠突变。使用来自TCGA的突变谱和患者生存数据的后勤回归模型,我们确定了EOC患者中特定的有害基因突变组是否会影响患者的生存.我们的结果表明,与生存时间增加密切相关的六个基因是BRCA1,NBN,BRIP1,RAD50,PTEN,PMS2此外,我们的分析表明,与减少生存时间密切相关的六个基因是FANCE,FOXM1KRAS,FANCD2,TTN,CSMD3此外,通过这些阳性和阴性基因突变特征分层的360例患者的Kaplan-Meier生存分析证实,我们的回归模型优于传统的基于HR基因的分类和生存结果预测。总的来说,我们的研究结果表明,EOC表现出超越HR基因突变的独特突变特征.我们的方法可以识别一组新的基因突变,有助于提高对EOC患者治疗结果和总体生存率的预测。
    Epithelial ovarian cancer (EOC) has a low overall survival rate, largely due to frequent recurrence and acquiring resistance to platinum-based chemotherapy. EOC with homologous recombination (HR) deficiency has increased sensitivity to platinum-based chemotherapy because platinum-induced DNA damage cannot be repaired. Mutations in genes involved in the HR pathway are thought to be strongly correlated with favorable response to treatment. Patients with these mutations have better prognosis and an improved survival rate. On the other hand, mutations in non-HR genes in EOC are associated with increased chemoresistance and poorer prognosis. For this reason, accurate predictions in response to treatment and overall survival remain challenging. Thus, analyses of 360 EOC cases on NCI\'s The Cancer Genome Atlas (TCGA) program were conducted to identify novel gene mutation signatures that were strongly correlated with overall survival. We found that a considerable portion of EOC cases exhibited multiple and overlapping mutations in a panel of 31 genes. Using logistical regression modeling on mutational profiles and patient survival data from TCGA, we determined whether specific sets of deleterious gene mutations in EOC patients had impacts on patient survival. Our results showed that six genes that were strongly correlated with an increased survival time are BRCA1, NBN, BRIP1, RAD50, PTEN, and PMS2. In addition, our analysis shows that six genes that were strongly correlated with a decreased survival time are FANCE, FOXM1, KRAS, FANCD2, TTN, and CSMD3. Furthermore, Kaplan-Meier survival analysis of 360 patients stratified by these positive and negative gene mutation signatures corroborated that our regression model outperformed the conventional HR genes-based classification and prediction of survival outcomes. Collectively, our findings suggest that EOC exhibits unique mutation signatures beyond HR gene mutations. Our approach can identify a novel panel of gene mutations that helps improve the prediction of treatment outcomes and overall survival for EOC patients.
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    文章类型: Journal Article
    UNASSIGNED: Thymoma-associated paraneoplastic syndromes in dogs and cats include myasthenia gravis, hypercalcemia, exfoliative dermatitis, erythema multiforme, T-cell lymphocytosis, myocarditis, anemia, and polymyositis. Paraneoplastic myasthenia gravis (MG) is the most commonly reported paraneoplastic syndrome in dogs with thymic epithelial tumors. The objective of this study was to examine cases of canine thymic-associated MG treated surgically, with the specific objective of providing an updated clinical picture of the preoperative management, postoperative complications, and outcomes of these cases.
    UNASSIGNED: Nine dogs with paraneoplastic MG underwent surgical removal of a thymic epithelial tumor.
    UNASSIGNED: Medical records of dogs with MG that received surgical treatment of a thymic epithelial tumor between January 1, 2012 and October 1, 2022 were obtained from 4 veterinary teaching hospitals. Descriptions of perioperative MG management, complications, and outcomes were reported.
    UNASSIGNED: Six of the 9 dogs received medical therapy for MG, with either a cholinesterase inhibitor (4 dogs) or a cholinesterase inhibitor and immunosuppressive agent (2 dogs), before surgery. The median duration of medical therapy for MG before surgery was 7.5 d (range: 2 to 60 d). Three of 9 dogs experienced immediate postoperative complications and were euthanized. Six of 9 dogs (66.6%) survived to discharge and 3 of 6 dogs that survived to discharge were alive at the time of writing. At the time of writing, 3 of 6 dogs had complete resolution of clinical signs attributable to MG and 2 of 6 had partial resolution. The median time from surgery to resolution of clinical signs of MG in these dogs was 63 d (range: 2 to 515 d).
    UNASSIGNED: Dogs with thymic epithelial tumors and paraneoplastic MG are at a high risk for perioperative complications.
    UNASSIGNED: The findings of this study corroborate previous literature stating that paraneoplastic MG is a poor prognostic indicator for dogs with thymic epithelial tumors, while also highlighting the variation in approaches to clinical management of thymic-associated MG in veterinary medicine and the lack of established protocols guiding perioperative management.
    Prise en charge préopératoire et complications postopératoires chez 9 chiens subissant un traitement chirurgical de la myasthénie grave associée au thymus.
    UNASSIGNED: Les syndromes paranéoplasiques associés au thymome chez le chien et le chat comprennent la myasthénie grave, l’hypercalcémie, la dermatite exfoliative, l’érythème polymorphe, la lymphocytose à cellules T, la myocardite, l’anémie et la polymyosite. La myasthénie paranéoplasique (MG) est le syndrome paranéoplasique le plus fréquemment rapporté chez les chiens atteints de tumeurs épithéliales thymiques. L’objectif de cette étude était d’examiner les cas de MG canine associée au thymus traités chirurgicalement, dans le but spécifique de fournir un tableau clinique actualisé de la prise en charge préopératoire, des complications postopératoires et des résultats de ces cas.
    UNASSIGNED: Neuf chiens atteints de MG paranéoplasique ont subi l’ablation chirurgicale d’une tumeur épithéliale thymique.
    UNASSIGNED: Les dossiers médicaux des chiens atteints de MG ayant reçu un traitement chirurgical d’une tumeur épithéliale thymique entre le 1er janvier 2012 et le 1er octobre 2022 ont été obtenues auprès de 4 hôpitaux universitaires vétérinaires. Des descriptions de la prise en charge péri-opératoire de la MG, des complications et des résultats ont été rapportées.
    UNASSIGNED: Six des 9 chiens ont reçu un traitement médical pour la MG, avec soit un inhibiteur de la cholinestérase (4 chiens), soit un inhibiteur de la cholinestérase et un agent immunosuppresseur (2 chiens), avant la chirurgie. La durée médiane du traitement médical de la MG avant la chirurgie était de 7,5 jours (plage : 2 à 60 jours). Trois des neuf chiens ont présenté des complications postopératoires immédiates et ont été euthanasiés. Six des 9 chiens (66,6 %) ont survécu jusqu’à leur sortie et 3 des 6 chiens qui ont survécu jusqu’à leur sortie étaient en vie au moment de la rédaction. Au moment de la rédaction de cet article, 3 chiens sur 6 présentaient une résolution complète des signes cliniques attribuables à la MG et 2 chiens sur 6 présentaient une résolution partielle. Le délai médian entre l’intervention chirurgicale et la résolution des signes cliniques de MG chez ces chiens était de 63 jours (plage : 2 à 515 jours).
    UNASSIGNED: Les chiens atteints de tumeurs épithéliales thymiques et de MG paranéoplasique présentent un risque élevé de complications périopératoires.
    UNASSIGNED: Les résultats de cette étude corroborent la littérature antérieure indiquant que la MG paranéoplasique est un indicateur de mauvais pronostic pour les chiens atteints de tumeurs épithéliales thymiques, tout en soulignant également la variation des approches de prise en charge clinique de la MG associée au thymus en médecine vétérinaire et le manque de protocoles établis de gestion guidant les interventions périopératoires.(Traduit par Dr Serge Messier).
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  • 文章类型: Journal Article
    背景:完全宏观切除(CMR)是延长卵巢癌生存期的关键因素。然而,大多数证据来自高级别浆液性卵巢癌(HGSOC),而CMR在其他组织型中的益处缺乏表征。我们试图确定哪些组织型从CMR中获得最大的益处,以更好地指导未来关于激进细胞还原努力的决定。
    方法:我们对两个独立的患者队列进行了疾病特异性生存(DSS)的多变量分析,以确定每个组织型中与CMR相关的获益程度。
    结果:在这两个队列中(苏格兰,n=1622;SEER,n=18947),CMR与长期DSS相关;这在苏格兰队列中更为明显(SEER的多变量HR0.44,95CI0.37-0.52vs0.59,95CI0.57-0.62)。在这两个队列中,透明细胞卵巢癌(CCOC)是最受益于CMR的组织学类型之一(苏格兰和SEER队列中的多变量HR0.23和0.50);HGSOC病例显示出非常显着和临床意义的生存获益,但在这两个队列中,这一幅度低于CCOC和子宫内膜样卵巢癌(EnOC).低级别浆液性卵巢癌的获益也很高(苏格兰队列中的多变量HR0.27)。在SEER队列中,CMR与粘液性卵巢癌(MOC)患者的生存期延长相关(多变量HR0.65),但相关因素在苏格兰队列中未能达到统计学意义。
    结论:总体卵巢癌患者群体表现出与CMR相关的显著生存获益;然而,不同组织型的获益程度不同。
    BACKGROUND: Complete macroscopic resection is a key factor associated with prolonged survival in ovarian cancer. However, most evidence derives from high-grade serous ovarian carcinoma, and the benefit of complete macroscopic resection in other histotypes is poorly characterized. We sought to determine which histotypes derive the greatest benefit from complete macroscopic resection to better inform future decisions on radical cytoreductive efforts.
    METHODS: We performed multivariable analysis of disease-specific survival across 2 independent patient cohorts to determine the magnitude of benefit associated with complete macroscopic resection within each histotype.
    RESULTS: Across both cohorts (Scottish: n = 1622; Surveillance, Epidemiology, and End Results [SEER]: n = 18 947), complete macroscopic resection was associated with prolonged disease-specific survival; this was more marked in the Scottish cohort (multivariable hazard ratio [HR] = 0.44, 95% confidence interval [CI] = 0.37 to 0.52 vs HR = 0.59, 95% CI = 0.57 to 0.62 in SEER). In both cohorts, clear cell ovarian carcinoma was among the histotypes to benefit most from complete macroscopic resection (multivariable HR = 0.23 and HR = 0.50 in Scottish and SEER cohorts, respectively); high-grade serous ovarian carcinoma patients demonstrated highly statistically significant and clinically meaningful survival benefit, but this was of lower magnitude than in clear cell ovarian carcinoma and endometrioid ovarian carcinoma across both cohorts. The benefit derived in low-grade serous ovarian carcinoma is also high (multivariable HR = 0.27 in Scottish cohort). Complete macroscopic resection was associated with prolonged survival in mucinous ovarian carcinoma patients in the SEER cohort (multivariable HR = 0.65), but the association failed to reach statistical significance in the Scottish cohort.
    CONCLUSIONS: The overall ovarian cancer patient population demonstrates clinically significant survival benefit associated with complete macroscopic resection; however, the magnitude of benefit differs between histotypes.
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