Interfaz inmunológica de la superficie ocular: expresión de MUC1, MUC4 y MUC16 y producción de citoquinas proinflamatorias en pacientes con síndrome de ojo seco secundario a enfermedad de Sjögren / Ocular surface immunological interface: expression of MUC1, MUC4 and MUC16 and production of proinflammatory cytokines in patients with dry eye syndrome secondary to Sjögren's disease

El síndrome de ojo seco (SOS) constituye una de las patologías oculares más frecuentes y con mayor repercusión en la calidad de vida de pacientes en el mundo actual. A su vez, dado cambios en los hábitos como el mayor uso de pantallas, la mayor polución y el envejecimiento poblacional hacen que la proyección sea en aumento. Se estima que el 10% de los SOS son pacientes con síndrome de Sjögren (SS). Este puede ser primario o secundario cuando se encuentra asociado a otras enfermedades del tejido conectivo como el lupus eritematoso sistémico (LES), la artritis reumatoide (AR) o la esclerosis sistémica (ES). El SOS secundario a SS (SS-SOS) nos resulta de particular interés por ser generalmente severo y de difícil tratamiento. El suero autólogo (SA) constituye una herramienta poco utilizada en nuestro medio hasta la realización de este proyecto. Sus componentes, que incluyen factores de crecimiento epitelial y vitamina A constituyen bloques fundamentales del mantenimiento de las barreras epiteliales haciéndolo una terapia prometedora y accesible. El SS es la tercera enfermedad reumática más prevalente junto con AR y el LES. Se estima que la prevalencia del SSP va del 0.1 al 4.8% de la población dependiendo de la edad, y 90% de estos pacientes son mujeres. A pesar de su alta prevalencia, aún hay gran desconocimiento de los mecanismos moleculares involucrados en el SS-SOS. Tanto la inmunidad innata como adaptativa participan en la patogenia del SOS asociado a SS. Estudios previos encontraron que tanto un perfil Th1 como Th17 serían los principales actores. Por este motivo, elegimos el estudio de las citoquinas IL-17 e IL-22 las cuales son las principales citoquinas efectoras de este perfil linfocitario. Estas citoquinas mantienen la integridad de la barrera epitelial estimulando la formación de proteínas que conforman las uniones estrechas.En especial IL-22 tiene un rol importante en la supervivencia y proliferación celular. Por su parte IL-17 tendría un rol estimulando la producción de péptidos antimicrobianos y quimioquinas que atraen leucocitos a la zona afectada cuando la barrera epitelial es penetrada. En la escasa literatura publicada se ha observado que los niveles de IL-17 e IL­22 se encuentran aumentados significativamente en pacientes con SS-SOS con relación a los no SS y a los controles sanos. A su vez, el nivel de estas citoquinas se correlacionaba positivamente con el cuestionario de queratopatía del índice de enfermedad de la superficie ocular (OSDI por su sigla en inglés) y negativamente con el tiempo de rotura del film lagrimal (TBUT por su sigla en inglés) y el resultado de la prueba de Schirmer. Debemos destacar que estos resultados fueron vistos en un único estudio que incluyó un pequeño número de pacientes. Las mucinas jugarían un rol fundamental en la homeostasis de la superficie ocular (SO). En particular las mucinas transmembrana MUC1, MUC4 y MUC16 estarían involucradas en la activación de factores de transcripción de citoquinas proinflamatorias. Nuestra hipótesis inicial era que se podría observar una disminución en la expresión de estas mucinas en relación con el daño de la SO. Esta hipótesis se basó en el conocido rol protector que las mucinas 12 juegan normalmente en las superficies epiteliales, atrapando agentes patógenos y su estudiada naturaleza inmunorreguladora. A lo largo de este trabajo de doctorado PROINBIO, se utilizó una combinación de diversas estrategias experimentales y clínicas para estudiar la superficie ocular en pacientes con síndrome de Sjögren (SS) y síndrome de ojo seco (SOS) y la correlación de estos hallazgos con la clínica del paciente.Para el desarrollo de este proyecto de investigación, conseguimos articular un servicio dirigido a los pacientes con SOS con la participación de un equipo multidisciplinario integrado por médicos oftalmólogos pertenecientes a la cátedra de oftalmología (valoración- seguimiento - indicación terapéutica), hemoterapia (desarrollo del colirio de suero autólogo) y unidad de enfermedades autoinmunes (captación de los pacientes con síndrome de Sjögren primario o secundario) del Hospital de Clínicas en Montevideo, Uruguay. Al mismo tiempo, desarrollamos y pusimos a punto la toma de biopsias de células conjuntivales mediante impresión conjuntival. Este procedimiento se había realizado anteriormente en nuestro medio, pero nunca para el estudio posterior con técnica de RT-PCR (reacción en cadena de la polimerasa en tiempo real). También conseguimos sistematizar el correcto almacenamiento y procesamiento de las muestras para la realización de esta técnica. Esto facilitará en el futuro continuar con el estudio de nuevos marcadores en esta y otras patologías de la SO. Nuestros resultados nos permitieron arribar a las siguientes conclusiones: Determinamos la primera estimación de prevalencia de SOS en una población de pacientes con diagnóstico de otras patologías autoinmunes en nuestra población la cual fue discretamente menor a la reportada en la literatura. Esta fue de 22% de los pacientes, constituyendo la primera estimación en Uruguay de SOS en pacientes con patología autoinmune. Logramos medir la expresión de las tres principales mucinas transmembrana de la SO en nuestro grupo de pacientes estudiados e individuos sanos. Contrario a nuestra hipótesis, observamos un aumento significativo de la expresión de MUC1 y MUC4 en nuestro grupo de pacientes con SOS.A pesar de que es conocido el rol fundamental de las mucinas en mantener la homeostasis de la SO, se ha descrito el aumento en la expresión de MUC1 y MUC4 frente al daño inflamatorio o en casos de neoplasias tanto en el epitelio digestivo como respiratorio. Detectamos una diferencia en la expresión de estas mucinas entre pacientes con SSP donde observamos un aumento de las tres mucinas de estudio (MUC1, MUC4 y MUC16) y SSS donde únicamente MUC1 se vio significativamente elevada. Asimismo, correlacionamos estos hallazgos con la clínica (síntomas y signos de ojo seco) observando que MUC4 correlaciona significativamente tanto con menor producción del film lagrimal como con un mayor grado de queratopatía superficial. La correlación de MUC4 con los síntomas de SOS no fue significativa lo cual pensamos sí se observaría probablemente incluyendo un mayor número de pacientes en el estudio. Por otra parte, MUC1 y MUC16 se correlacionaron positivamente con una presencia de síntomas más severos de SOS pero su correlación con los signos clínicos de SOS no llegó al nivel de significancia excepto en el caso de MUC1 con relación al grado de queratopatía. Evaluamos la expresión de citoquinas proinflamatorias del perfil Th17 como son IL-17 e IL-22. Observamos como la IL 22 se correlaciona con la expresión de MUC16, la cual a su vez aumenta en pacientes con mayor sintomatología de SOS. Encontramos una correlación significativa entre la expresión de ambas citoquinas como era esperable ya que ambas son citoquinas que corresponden a un mismo perfil de respuesta linfocitaria. No pudimos reproducir los resultados vistos en la literatura, aunque escasa, la cual reporta que los pacientes con SOS presentan un aumento de estas citoquinas en relación a una mayor severidad clínica del SS-SOS.En nuestro estudio no observamos diferencia entre nuestro grupo de pacientes y el grupo control ni una correlación con los síntomas o signos del SOS. Analizamos la expresión de MUC1, MUC4 y MUC16 comparando el grupo de pacientes con SS tratados con inmunomoduladores versus los no tratados observando una diferencia interesante entre estos dos grupos. Mientras ambos grupos sobre expresan MUC1. Los pacientes en tratamiento presentan un aumento de MUC4 y no de MUC16 y lo inverso se observa en los pacientes no tratados. Evidenciamos la mejoría sintomática del tratamiento de estos pacientes con suero autólogo al 20% el cual es una opción terapéutica disponible en nuestro medio que está subutilizada por la falta de evidencia clínica hasta el momento. Estos resultados son un sustento objetivo de la efectividad del tratamiento para este grupo de pacientes. En suma, este trabajo constituye una aproximación a comprender como varia la expresión a nivel de ARN mensajero de mucinas transmembranarias específicas y su asociación con citoquinas de perfil Th17, así como síntomas y signos clínicos del SS-SOS. Constituye un gran paso inicial a la caracterización molecular de la SO de estos pacientes y con esta la potencialidad de desarrollar terapias dirigidas. Según nuestro saber y entender, éste constituye el primer trabajo de estas características en nuestro medio y nos brinda más información de la prevalencia y características de estos pacientes en Uruguay. La puesta a punto de la técnica de impresión conjuntival, conocida en el mundo, pero no utilizada en nuestro país habitualmente para la extracción de ARN, abre las puertas para ampliar nuestras investigaciones focalizándonos en otras moléculas posiblemente cruciales en el desarrollo de SOS como por ejemplo el estudio de glicosil transferasas.

Índice de irresecabilidad asociado a citorreducción óptima en pacientes con cáncer de ovario: Estudio observacional de centro único / Unresectability index associated with optimal cy-toreduction in patients with ovarian cancer: A single-center observational study

Introducción: El índice de irresecabilidad valora la presencia de cuatro variables (masa abdominal palpable, tumor en fondo de saco de Douglas, presencia de líquido ascítico, valor preoperatorio de Ca 125 mayor a 1000 U/ml); previo a la realización de una cirugía citorreductora primaria en pacientes con cáncer de ovario. El objetivo del presente estudio fue realizar una prueba diagnóstica del índice de irresecabilidad con la decisión de realizar citorreducción óptima en pacientes con cáncer de ovario que fueron operadas en un hospital público de referencia nacional en Ecuador en 3 años de estudio. Metodología: En el presente estudio de pruebas diagnósticas, se estudiaron mujeres operadas con cáncer de ovario, en el Hospital de Especialidades Eugenio Espejo (Ecuador) de septiembre del 2016 a septiembre del 2018. Se incluyeron pacientes con citorreducción óptima y subóptima. Se presenta un análisis descriptivo con frecuencias, porcentajes y promedios. Se evaluó la sensibilidad, especificidad, valor predictivo negativo (VPN) y valor predictivo positivo (VPP) del índice de irresecabilidad comparado con la citorreducción. Resultados: Fueron 148 casos analizados. La especificidad del índice fue de 81 %, con un valor predictivo (VP) positivo del 77 % y VP negativo de 68 %. La sensibilidad de la ascitis 85 % y la masa abdominal palpable del 79 %. En las pacientes que presentaron valores de antígeno CA-125 menor a 1000 U/ml, el riesgo de obtener una citorreducción óptima fue OR: 0.15 (IC95% 0.069 ­ 0.307; P: 0.0001); las pacientes que presentaron valores del índice de irresecabilidad entre 1 y 2 puntos versus 3 y 4 fue de OR: 7.04 (IC95% 3.33 -14.87, P: 0.0001). Conclusiones: El Índice de irresecabilidad presentó una capacidad estadísticamente significativa para predecir citorreducción óptima en las pacientes con cáncer ovario operadas en el Hospital de Especialidades Eugenio Espejo.

Introduction: The unresectability index assesses the presence of four variables (palpable abdominal mass, tumor in the fornix of Douglas, presence of ascitic fluid, preoperative Ca 125 value greater than 1000 U/ml); before performing primary cytoreductive surgery in patients with ovarian cancer. The objective of this study was to carry out a diagnostic test of the unresectability index with the decision to perform optimal cytoreduction in patients with ovarian cancer who underwent surgery in a public hospital of national reference in Ecuador in 3 years of study. Methodology: In the present study of diagnostic tests, women operated on for ovarian cancer were studied at the Eugenio Espejo Specialties Hospital (Ecuador) from September 2016 to September 2018. Patients with optimal and suboptimal cytoreduction were included. A descriptive analysis with frequencies, percentages, and averages is presented. The sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) of the unresectable index compared with cytoreduction were evaluated. Results: 148 cases were analyzed. The specificity of the index was 81%, with a positive predictive value (PV) of 77% and a negative PV of 68%. The sensitivity of ascites is 85%, and the palpable abdominal mass of 79%. In patients who presented CA-125 antigen values less than 1000 U/ml, the risk of obtaining optimal cytoreduction was OR: 0.15 (95% CI 0.069 - 0.307; P: 0.0001); The patients who presented unresectability index values between 1 and 2 points versus 3 and 4 were OR: 7.04 (95% CI 3.33 -14.87, P: 0.0001). Conclusions: The unresectability index presented a statistically significant capacity to predict optimal cytoreduction in patients with ovarian cancer operated on at the Eugenio Espejo Specialties Hospital.

Study on the predictive significance of PLR, SII and RPR in ovarian endometriotic cyst / 中华妇产科杂志

Objective: To investigate the predictive value of platelet-to-lymphocyte ratio (PLR), red blood cell distribution width to platelet count ratio (RPR) and systemic immune inflammation index (SII) in the staging and postoperative recurrence of ovarian endometrial cysts. Methods: Retrospective analysis was made on the clinical data of patients who underwent laparoscopic surgery for ovarian cysts in the Affiliated Hospital of Qingdao University from January 2018 to January 2020. The patients with ovarian endometriosis cyst confirmed by pathology after surgery were the observation group (n=350), and the patients with other benign ovarian cyst were the control group (n=150). The preoperative platelet count, platelet distribution width, absolute number of neutrophils, lymphocyte absolute number, absolute number of monocytes, red blood cell distribution width, and serum cancer antigen 125 (CA125) of the patients in two groups were recorded, and PLR, neutrophil-to-lymphocyte ratio (NLR), RPR, SII, and systemic inflammation response index (SIRI) were calculated and analyzed. The general data of all patients and the follow-up data within 2 years after the operation of the observation group were statistically recorded to evaluate the diagnostic value of PLR, RPR and SII for ovarian endometrial cyst, and the predictive value of staging and recurrence within 2 years after the operation. Results: PLR, NLR, SII (median: 147.53, 1.86, and 488.70 respectively) and CA125 (median: 59.41 kU/L) in the observation group were significantly higher than those in the control group, while RPR (median: 0.16) was lower than that in the control group, with significant differences (all P<0.01). There was no significant difference in SIRI between the two groups (P>0.05). The PLR and SII (median: 122.73, 345.00) of the observation group at stage Ⅲ and Ⅳ were higher than those of patients at stage Ⅰ and Ⅱ, and the RPR was lower than that of patients with stage Ⅰ and Ⅱ, with significant differences (all P<0.001). The PLR, NLR, SII, SIRI (median: 179.63, 2.75, 762.96, and 1.06 respectively) and CA125 (median: 108.83 kU/L) in patients with recurrence were significantly higher than those in patients without recurrence 2 years after the operation, and the differences were statistically significant (all P<0.001). The area under curve (AUC) of CA125 in the diagnosis of ovarian endometriosis cyst was 0.951, the sensitivity was 85.7%, and the specificity was 93.0%, which were higher than those of PLR and SII; the AUC of PLR+SII+CA125 in the diagnosis of ovarian endometriosis cyst was 0.952. The AUC of RPR predicting the stage of ovarian endometriosis cyst was 0.713, higher than PLR and SII, lower than CA125; the AUC of RPR+SII+CA125 in predicting the stage of ovarian endometriotic cyst was 0.825, with sensitivity of 68.7% and specificity of 85.7%. The AUC predicted by SII for recurrence of ovarian endometriotic cyst within 2 years after the operation was 0.803, higher than NLR, PLR, SIRI and CA125; the AUC of PLR+SII+CA125, sensitivity, specificity was 0.813, 81.5% and 73.0%, higher than SII. Conclusion: PLR, RPR and SII are related to the staging of ovarian endometriotic cyst, and SII has a certain predictive value for the recurrence of ovarian endometriotic cyst after surgery.

Struma Ovarii com Síndrome Pseudo-Meigs e Aumento dos Níveis de CA-125: Relato de Caso / Struma Ovarii with Pseudo-Meigs Syndrome and Increased CA-125 Levels: Case Report / Struma Ovarii com Síndrome Pseudo-Meigs e Aumento dos Níveis de CA-125: Relato de Caso

Struma ovarii is a rare type of ovarian tumor composed of more than 50% of thyroid tissue. It represents only 1% of solid ovarian tumors and 3% of dermoid subtypes, with the majority of cases following a benign course. It typically affects women between the third and fifth decades of life and often remains asymptomatic or presents with nonspecific signs. pseudo-Meigs syndrome, characterized by ascites and pleural effusion, may be present, complicating the diagnosis. Case report: A 43-year-old woman presented with abdominal discomfort, pelvic pain, and chronic dyspnea. A CT scan identified a solid-cystic pelvic mass, moderate ascites, and right-sided pleural effusion. Magnetic resonance imaging (MRI) confirmed the findings, raising suspicion of malignant ovarian tumor. The serum tumor marker CA-125 was elevated. The patient underwent exploratory laparotomy, resulting in bilateral salpingo-oophorectomy. Histopathological analysis of the specimen confirmed the diagnosis of struma ovarii in the left ovary and mature cystic teratoma in the right ovary. Conclusion: Elevated CA-125 levels can be found in cases of struma ovarii, posing a differential diagnosis challenge with malignant ovarian neoplasms, especially when associated with pseudo-Meigs syndrome. Therefore, although rare, it should be considered as a possibility during clinical investigation of ovarian masses with atypical presentations. Imaging studies can assist, but confirmation is established through microscopic analysis. Treatment involves simple surgical resection, and symptom disappearance follows, with favorable prognosis

Struma ovarii é um tipo raro de tumor ovariano composto por mais de 50% de tecido tireoidiano. Representa apenas 1% dos tumores sólidos do ovário e 3% dos subtipos dermoides, com a maioria dos casos de curso benigno. Geralmente afeta mulheres entre a terceira e a quinta décadas de vida, sendo muitas vezes assintomático ou com sinais inespecíficos. A síndrome de pseudo-Meigs, caracterizada por ascite e derrame pleural, pode estar presente, dificultando o diagnóstico. Relato do caso: Mulher, 43 anos, com desconforto abdominal, dor pélvica e dispneia crônica. A tomografia identificou massa sólido-cística na pelve e ascite moderada, além de derrame pleural à direita. A ressonância magnética confirmou as alterações e, desse modo, suspeitou-se de tumor maligno ovariano. O marcador sérico tumoral CA-125 estava elevado. A paciente foi submetida a uma laparotomia exploradora que resultou em salpingo-oforectomia bilateral. A análise histopatológica do espécime confirmou o diagnóstico de struma ovarii em ovário esquerdo e teratoma cístico maduro à direita. Conclusão: Os níveis elevados de CA-125 podem ser encontrados em casos de struma ovarii, tornando-o diagnóstico diferencial nas neoplasias ovarianas malignas, especialmente quando associado à síndrome de pseudo-Meigs. Nesse sentido, embora raro, o tumor deve ser considerado uma possibilidade durante investigação clínica de massas ovarianas com apresentações atípicas. Os exames de imagem podem auxiliar, mas a confirmação é estabelecida pela análise microscópica. O tratamento consiste na ressecção cirúrgica simples, e o desaparecimento dos sintomas acontece em seguida, sendo de bom prognóstico.

El struma ovarii es un tipo raro de tumor ovárico compuesto por más del 50% de tejido tiroideo. Representa solo el 1% de los tumores ováricos sólidos y el 3% de los subtipos dermoides, siendo en su mayoría benigno. Típicamente afecta a mujeres entre la tercera y quinta década de vida y a menudo permanece asintomático o presenta signos inespecíficos. El síndrome de pseudo-Meigs, caracterizado por ascitis y derrame pleural, puede estar presente, complicando el diagnóstico. Informe del caso: Una mujer de 43 años consultó por malestar abdominal, dolor pélvico y disnea crónica. La tomografía identificó una masa pélvica sólido-quística, ascitis moderada y derrame pleural en el lado derecho. La resonancia magnética confirmó los hallazgos, levantando sospechas de un tumor ovárico maligno. El marcador tumoral sérico CA-125 estaba elevado. La paciente fue sometida a una laparotomía exploratoria, resultando en salpingo-ooforectomía bilateral. El análisis histopatológico de la muestra confirmó el diagnóstico de struma ovarii en el ovario izquierdo y teratoma quístico maduro en el ovario derecho. Conclusión: Los niveles elevados de CA-125 pueden encontrarse en casos de struma ovarii, lo que lo convierte en diagnóstico diferencial con neoplasias ováricas malignas, especialmente cuando se asocia con el síndrome de pseudo-Meigs. Por lo tanto, aunque sea raro, se debe considerar como una posibilidad durante la investigación clínica de masas ováricas con presentaciones atípicas. Los estudios por imágenes pueden ayudar, pero la confirmación se establece mediante análisis microscópico. El tratamiento implica la resección quirúrgica simple y los síntomas desaparecen después, con un pronóstico favorable.

Struma Ovarii com Síndrome Pseudo-Meigs e Aumento dos Níveis de CA-125: Relato de Caso / Struma Ovarii with Pseudo-Meigs Syndrome and Increased CA-125 Levels: Case Report / Struma Ovarii con Síndrome de Pseudo-Meigs y Niveles Elevados de CA-125: Informe de Caso

Introdução: Struma ovarii é um tipo raro de tumor ovariano composto por mais de 50% de tecido tireoidiano. Representa apenas 1% dos tumores sólidos do ovário e 3% dos subtipos dermoides, com a maioria dos casos de curso benigno. Geralmente afeta mulheres entre a terceira e a quinta décadas de vida, sendo muitas vezes assintomático ou com sinais inespecíficos. A síndrome de pseudo-Meigs, caracterizada por ascite e derrame pleural, pode estar presente, dificultando o diagnóstico. Relato do caso: Mulher, 43 anos, com desconforto abdominal, dor pélvica e dispneia crônica. A tomografia identificou massa sólido-cística na pelve e ascite moderada, além de derrame pleural à direita. A ressonância magnética confirmou as alterações e, desse modo, suspeitou-se de tumor maligno ovariano. O marcador sérico tumoral CA-125 estava elevado. A paciente foi submetida a uma laparotomia exploradora que resultou em salpingo-oforectomia bilateral. A análise histopatológica do espécime confirmou o diagnóstico de struma ovarii em ovário esquerdo e teratoma cístico maduro à direita. Conclusão: Os níveis elevados de CA-125 podem ser encontrados em casos de struma ovarii, tornando-o diagnóstico diferencial nas neoplasias ovarianas malignas, especialmente quando associado à síndrome de pseudo-Meigs. Nesse sentido, embora raro, o tumor deve ser considerado uma possibilidade durante investigação clínica de massas ovarianas com apresentações atípicas. Os exames de imagem podem auxiliar, mas a confirmação é estabelecida pela análise microscópica. O tratamento consiste na ressecção cirúrgica simples, e o desaparecimento dos sintomas acontece em seguida, sendo de bom prognóstico

Introduction: Struma ovarii is a rare type of ovarian tumor composed of more than 50% of thyroid tissue. It represents only 1% of solid ovarian tumors and 3% of dermoid subtypes, with the majority of cases following a benign course. It typically affects women between the third and fifth decades of life and often remains asymptomatic or presents with nonspecific signs. pseudo-Meigs syndrome, characterized by ascites and pleural effusion, may be present, complicating the diagnosis. Case report: A 43-year-old woman presented with abdominal discomfort, pelvic pain, and chronic dyspnea. A CT scan identified a solid-cystic pelvic mass, moderate ascites, and right-sided pleural effusion. Magnetic resonance imaging (MRI) confirmed the findings, raising suspicion of malignant ovarian tumor. The serum tumor marker CA-125 was elevated. The patient underwent exploratory laparotomy, resulting in bilateral salpingo-oophorectomy. Histopathological analysis of the specimen confirmed the diagnosis of struma ovarii in the left ovary and mature cystic teratoma in the right ovary. Conclusion: Elevated CA-125 levels can be found in cases of struma ovarii, posing a differential diagnosis challenge with malignant ovarian neoplasms, especially when associated with pseudo-Meigs syndrome. Therefore, although rare, it should be considered as a possibility during clinical investigation of ovarian masses with atypical presentations. Imaging studies can assist, but confirmation is established through microscopic analysis. Treatment involves simple surgical resection, and symptom disappearance follows, with favorable prognosis.

Introducción: El struma ovarii es un tipo raro de tumor ovárico compuesto por más del 50% de tejido tiroideo. Representa solo el 1% de los tumores ováricos sólidos y el 3% de los subtipos dermoides, siendo en su mayoría benigno. Típicamente afecta a mujeres entre la tercera y quinta década de vida y a menudo permanece asintomático o presenta signos inespecíficos. El síndrome de pseudo-Meigs, caracterizado por ascitis y derrame pleural, puede estar presente, complicando el diagnóstico. Informe del caso: Una mujer de 43 años consultó por malestar abdominal, dolor pélvico y disnea crónica. La tomografía identificó una masa pélvica sólido-quística, ascitis moderada y derrame pleural en el lado derecho. La resonancia magnética confirmó los hallazgos, levantando sospechas de un tumor ovárico maligno. El marcador tumoral sérico CA-125 estaba elevado. La paciente fue sometida a una laparotomía exploratoria, resultando en salpingo-ooforectomía bilateral. El análisis histopatológico de la muestra confirmó el diagnóstico de struma ovarii en el ovario izquierdo y teratoma quístico maduro en el ovario derecho. Conclusión: Los niveles elevados de CA-125 pueden encontrarse en casos de struma ovarii, lo que lo convierte en diagnóstico diferencial con neoplasias ováricas malignas, especialmente cuando se asocia con el síndrome de pseudo-Meigs. Por lo tanto, aunque sea raro, se debe considerar como una posibilidad durante la investigación clínica de masas ováricas con presentaciones atípicas. Los estudios por imágenes pueden ayudar, pero la confirmación se establece mediante análisis microscópico. El tratamiento implica la resección quirúrgica simple y los síntomas desaparecen después, con un pronóstico favorable.

MUC16: The Novel Target for Tumor Therapy / 中国肺癌杂志

Mucin16 (MUC16), also known as carbohydrate antigen 125 (CA125), is a glycoprotein antigen that can be recognized by the monoclonal antibody OC125 detected from epithelial ovarian carcinoma antigen by Bast et al in 1981. CA125 is not present in normal ovarian tissue but is usually elevated in the serum of epithelial ovarian carcinoma patients. CA125 is the most commonly used serologic biomarker for the diagnosis and recurrence monitoring of epithelial ovarian carcinoma. MUC16 is highly expressed in varieties of tumors. MUC16 can interact with galectin-1/3, mesothelin, sialic acid-binding immunoglobulin-type lectins-9 (Siglec-9), and other ligands. MUC16 plays an important role in tumor genesis, proliferation, migration, invasion, and tumor immunity through various signaling pathways. Besides, therapies targeting MUC16 have some significant achievements. Related preclinical studies and clinical trials are in progress. MUC16 may be a potential novel target for tumor therapy. This article will review the mechanism of MUC16 in tumor genesis and progression, and focus on the research actuality of MUC16 in tumor therapy. This article also provides references for subsequent tumor therapy studies targeting MUC16.
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CA-125 and CCL2 may indicate inflammation in peritoneal dialysis patients / CA-125 e CCL2 podem indicar inflamação em pacientes em diálise peritoneal

Abstract Introduction: Progressive structural changes in the peritoneal membrane occur over the course of treatment in peritoneal dialysis (PD), resulting in an increase in cytokines such as CCL2 and structural changes in peritoneal membrane triggering an increase in CA-125 in dialysate, which reflects a probable local inflammatory process, with possible loss of mesothelial cells. Thus, the current study aimed to evaluate the association between plasma and CCL2 and CA-125 dialysate levels in patients undergoing PD. Methods: Cross-sectional study was conducted with 41 patients undergoing PD. The assessments of CA-125 and CCL2 levels were performed using a capture ELISA. Correlations were estimated using Spearman's correlation and the investigation of the association between the explanatory variables (CCL2) and response variable (CA-125) was done for crude ratio of arithmetic means and adjusted utilizing generalized linear models. Results: A moderate positive correlation was observed between the levels of CA-125 and CCL2 in the dialysate (rho = 0.696). A statistically significant association was found between the levels in the CCL2 and CA-125 dialysate (RoM=1.31; CI = 1.20-1.43), which remained after adjustment for age (RoM = 1.31; CI=1.19-1.44) and for time in months of PD (RoM=1.34, CI=1.22-1.48). Conclusion: The association of CA-125 levels with CCL2 in the dialysate may indicate that the local inflammatory process leads to temporary or definitive changes in peritoneal membrane. A better understanding of this pathogenesis could contribute to the discovery of new inflammatory biomarkers.

Resumo Introdução: Alterações estruturais progressivas na membrana peritoneal ocorrem no decorrer do tratamento em diálise peritoneal (DP), resultando em um aumento de citocinas como CCL2 e alterações estruturais na membrana peritoneal desencadeando um aumento de CA-125 no dialisato, o que reflete um provável processo inflamatório local, com possível perda de células mesoteliais. Assim, o presente estudo teve como objetivo avaliar a associação entre CCL2 e CA-125 no plasma e no dialisato de pacientes submetidos à DP. Métodos: Foi realizado um estudo transversal com 41 pacientes submetidos à DP. As avaliações dos níveis de CA-125 e CCL2 foram realizadas utilizando ELISA de captura. As correlações foram estimadas usando a correlação de Spearman, e a investigação da associação entre as variáveis explicativas (CCL2) e a variável resposta (CA-125) foi feita pela razão bruta das médias aritméticas e ajustada utilizando modelos lineares generalizados. Resultados: Foi observada uma correlação positiva moderada entre os níveis de CA-125 e CCL2 no dialisato (rho = 0,696). Foi encontrada uma associação estatisticamente significativa entre os níveis no dialisato de CCL2 e CA-125 (RoM=1,31; IC = 1,20-1,43), que permaneceu após ajuste por idade (RoM = 1,31; IC=1,19-1,44) e pelo tempo de DP em meses (RoM=1,34, IC=1,22-1,48). Conclusão: A associação dos níveis de CA-125 com CCL2 no dialisato pode indicar que o processo inflamatório local leva a alterações temporárias ou definitivas na membrana peritoneal. Uma melhor compreensão desta patogênese pode contribuir para a descoberta de novos biomarcadores inflamatórios.

CA 125 elevado en contexto de endometrioma: reporte de caso / Elevated CA 125 in the context of endometrioma: case report

Introducción: Los tumores benignos de ovario corresponden a un 60-95% de las lesiones anexiales, en edad fértil los más frecuentes corresponden a quistes foliculares y endometriomas. Sin embargo, alrededor del 15% son patología maligna de ovario. Por lo que se debe evaluar aspectos como edad, características ecográficas y la presencia de marcadores tumorales específicos como CA 125. Objetivo general: Describir un reporte de caso y caracterizar la evidencia disponible sobre el abordaje de tumores benignos de ovario. Caso Clínico: Se presenta el caso clínico de una paciente en edad fértil de 43 años, cursando con dolor abdominal asociado a masa anexial, donde destaca la elevación del marcador CA 125 en rango de malignidad, por lo que se solicita valoración por oncología y manejo quirúrgico, confirmándose una masa anexial benigna de características quísticas, sugerente de endometrioma, al descartar patología maligna se realiza quistectomía total. Discusión: La patología anexial es una entidad clínica que puede abarcar características tumorales, ya sean benignas como malignas, por ello frente a lesiones ováricas, siempre se deben descartar estas últimas. Las características ecográficas de la paciente hacían sospechar de un endometrioma, el CA 125 elevado en ella hizo que se optara por un manejo quirúrgico oncológico con biopsia rápida para descartar o confirmar malignidad. Conclusión: Ante la presencia de endometriomas, el tratamiento debe discutirse caso a caso, teniendo en cuenta la sintomatología, deseos de fertilidad futura y tamaño de las lesiones.

Introduction: Benign ovarian tumors correspond to 60-95% of adnexal lesions, in childbearing years the most frequent correspond to follicular cysts and endometriomas. However, about 15% are malignant ovarian pathology. Therefore, aspects such as age, ultrasound characteristics and the presence of specific tumor markers such as CA 125 must be evaluated. General objective: Describe a case report and characterize the available evidence on benign ovarian tumors. Case report: A case of a 43 year old female of childbearing age, presents abdominal pain associated with an adnexal mass, where CA 125 elevations are found in the range of malignancy, for which an oncology evaluation and surgical management. A benign adnexal mass with cystic characteristics is confirmed, suggestive of endometrioma, when malignant pathology is ruled out, a total cystectomy is performed. Discussion: Adnexal pathology is a clinical entity that can include tumor characteristicas, whether benign or malignant, therefore, in the face of ovarian lesions, these should always be ruled out. The sonographic characteristics of the patient made one suspect an endometrioma, the elevated CA 125 in it led to an oncological surgical management with rapid biopsy to rule out or confirm malignancy. Conclusions: In the presence of endometriomas, treatmentshould be discussed individually, taking into account the symptoms, wishes for future fertility, and size of the lesions. Keywords: Ca-125 antigen, Endometriosis, Ovarian neoplasms

Serum levels of soluble interleukin-2 receptor (sIL-2R) and cancer antigen 125 (CA 125) in dogs diagnosed with cutaneous lymphoma / [Níveis séricos do receptor solúvel de interleucina-2 (sIL-2R) e antígeno do câncer 125 (CA 125) em cães diagnosticados com linfoma cutâneo]

Marcadores sorológicos são rotineiramente utilizados na prática clínica para o estadiamento de linfomas e para a determinação de seu prognóstico em humanos. No entanto, pouco se sabe sobre sua utilização em cães, mesmo os linfomas sendo neoplasias com alta prevalência nessa espécie. No presente estudo, as concentrações séricas do receptor solúvel de interleucina-2 (sIL-2R) e do antígeno do câncer 125 (CA 125) foram mensurados em 10 cães saudáveis e em 15 cães com linfoma cutâneo, utilizando-se o kit ELISA canino e a leitura em um Stat Fax modelo 2100 (sIL-2R), bem como o kit ELISA humano e a leitura pelo ELISYS UNO humano (CA 125). Os resultados mostraram que não houve diferença significativa (P<0,05) nas concentrações dos marcadores entre os grupos. Além disso, os resultados não apontaram significância clínica no estadiamento tumoral e estabelecimento do prognóstico em cães diagnosticados com linfoma cutâneo.(AU)

Postoperative transient elevation of serum cancer antigen 125 in non-small cell lung cancer patients

SUMMARY OBJECTIVE: The aim of this retrospective study was to investigate the correlation of transiently elevated postoperative serum cancer antigen 125 levels and prognosis in patients with non-small cell lung cancer. METHODS: A total of 181 non-small cell lung cancer patients with normal levels of preoperative serum cancer antigen 125 were statistically summarized in this study. RESULTS: Out of the analyzed patients, 22 (12.2%) showed elevation of serum cancer antigen 125 within one month after surgery. Serum cancer antigen 125 level decreased to normal at three months postoperation. Serum cancer antigen 125 was positively correlated with pro-brain natriuretic peptide in non-small cell lung cancer postoperative patients (p=0.00035). Univariate analysis did not find significant difference in disease progression survival between those who experienced cancer antigen 125 elevation in the early postoperation and those who did not (p=0.646). CONCLUSIONS: In conclusion, transient elevation of cancer antigen 125 is associated to pro-brain natriuretic peptide increase after pulmonary surgery in non-small cell lung cancer patients.

Struma ovarii-associated pseudo-Meigs−syndrome with concomitant abdominopelvic tuberculosis masquerading as ovarian malignancy / Philippine Journal of Obstetrics and Gynecology

@#Pseudo-Meigs' syndrome (PMS) is a rare disease characterized by the triad of (1) an ovarian neoplasm, other than a fibroma or thecoma, (2) ascites, and (3) pleural effusion. Tumors such as struma ovarii, mucinous and serous cystadenomas, and germ cell tumors have been linked with the condition. Due to its clinical features combined with the elevation of serum cancer antigen 125 (CA-125) levels, it is often mistaken and treated as a malignant ovarian tumor. Ascites or pleural effusion could be massive leading to various life-threatening complications. Despite its presentation, this entity has an excellent prognosis when surgical excision of the tumor is performed. This article presents an unusual case of a 41-year-old gravida 10 para 10 (10-0-0-9) who was diagnosed with a case of struma ovarii associated PMS with concomitant abdominopelvic tuberculosis and elevated CA-125 resembling an ovarian malignancy.

Preoperative differentiation of benign and malignant non-epithelial ovarian tumors: clinical features and tumor markers / Diferenciação pré-operatória de tumores ovarianos não epiteliais benignos e malignos: características clínicas e marcadores tumorais

Abstract Objective To evaluate the role of clinical features and preoperativemeasurement of cancer antigen 125 (CA125), human epididymis protein(HE4), and carcinoembryonic antigen (CEA) serum levels in women with benign and malignant non-epithelial ovarian tumors. Methods One hundred and nineteen consecutive women with germ cell, sex cordstromal, and ovarian leiomyomas were included in this study. The preoperative levels of biomarkers were measured, and then surgery and histopathological analysis were performed. Information about the treatment and disease recurrence were obtained from the medical files of patients. Results Our sample included 71 women with germ cell tumors (64 benign and 7 malignant), 46 with sex cord-stromal tumors (32 benign and 14 malignant), and 2 with ovarian leiomyomas. Among benign germ cell tumors, 63 were mature teratomas, and, amongmalignant, fourwere immatureteratomas. Themost common tumors in the sex cordstromal group were fibromas (benign) and granulosa cell tumor (malignant). The biomarker serum levels were not different among benign andmalignant non-epithelial ovarian tumors. Fertility-sparing surgeries were performed in 5 (71.4%) women with malignant germ cell tumor. Eleven (78.6%) patients with malignant sex cord-stromal tumors were treated with fertility-sparing surgeries. Five women (71.4%) with germ cell tumors and only 1 (7.1%) with sex cord-stromal tumor were treated with chemotherapy. One woman with germ cell tumor recurred and died of the disease and one woman with sex cord-stromal tumor recurred. Conclusion Non-epithelial ovarian tumors were benign in the majority of cases, and the malignant caseswere diagnosed at initial stages with good prognosis. Themeasurements of CA125, HE4, and CEA serum levels were not useful in the preoperative diagnosis of these tumors.

Resumo Objetivo Avaliar o papel das características clínicas e a medida pré-operatória dos níveis séricos de CA125, HE4, e CEA em mulheres com tumores de ovário não epiteliais benignos e malignos. Métodos Cento e dezenovemulheres consecutivas comtumores ovarianos de células germinativas, do cordão sexual-estroma, e miomas ovarianos foram incluídas neste estudo. Os níveis pré-operatórios dos biomarcadores foram medidos, a cirurgia e a análise histopatológica foram realizadas. Informações sobre tratamento e recorrência da doença foram obtidas dos prontuários médicos das pacientes. Resultados Nossa amostra incluiu 71 mulheres com tumores de células germinativas (64 benignos e 7 malignos), 46 com tumores do cordão sexual-estroma (32 benignos e 14 malignos), e 2 com leiomiomas ovarianos. Entre os tumores benignos de células germinativas, 63 eram teratomas maduros, e, entre os malignos, quatro eram teratomas imaturos. Os tumores mais comuns do grupo do cordão sexual-estroma foram fibromas (benignos) e tumores de células da granulosa (malignos). Os níveis séricos dos biomarcadores não diferiram entre os tumores de ovário não epiteliais benignos e malignos. A cirurgia preservadora de fertilidade foi realizada em 5 (71,4%) mulheres com tumores malignos de células germinativas. Onze (78,6%) mulheres com tumores do cordão sexual-estromamalignos foram tratadas comcirurgia preservadora de fertilidade. Cinco (71,4%)mulheres com células germinativas e apenas 1 (7,1%) com tumor do cordão sexual-estroma foram tratadas com quimioterapia. Uma mulher com tumor de células germinativas recidivou e morreu da doença. Uma mulher com tumor do cordão sexual-estroma recidivou. Conclusão Os tumores de ovário não epiteliais foram benignos namaioria dos casos e os malignos foram diagnosticados em estágios iniciais, com bom prognóstico. A medida dos níveis séricos de CA125, HE4, e CEA não foram úteis no diagnóstico préoperatório desses tumores.

Diagnostic value of the neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, and thrombocytosis in the preoperative investigation of ovarian masses / Valor diagnóstico das razões neutrófilo/linfócito, plaqueta/ linfócito, e trombocitose na investigação pré-operatória de massas ovarianas

Abstract Objective To evaluate the diagnostic accuracy of cancer antigen 125 (CA125) and complete blood count (CBC) parameters, such as the neutrophil to lymphocyte ratio (NLR), the platelet to lymphocyte ratio (PLR), and thrombocytosis in patients with ovarian masses. Methods The present is a retrospective study conducted at a single tertiary hospital from January 2010 to November 2016. We included consecutive women referred due to suspicious adnexal masses. The CBC and CA125 were measured in the serum of 528 women with ovarian masses before surgery or biopsy. We evaluated the diagnostic performance of the NLR, PLR, platelets (PLTs), CA125, and the associations between them. We tested the clinical utility of the CBC parameters and CA125 in the discrimination of ovarian masses through decision curve analysis (DCA). Results The best balance between sensitivity and specificity was obtained by the associations of CA125 or PLTs ≥ 350/nL, with 70.14% and 71.66%, CA125 or PLTs ≥ 400/ nL, with 67.30% and 81.79%, CA125 or PLR, with 76.3% and 64.87%, and CA125 or NLR, with 71.09% and 73.89% respectively. In the DCA, no isolated CBC parameter presented a higher clinical utility than CA125 alone. Conclusion We showed that no CBC parameter was superior to CA125 in the prediction of the malignancy of ovarian tumors in the preoperative scenario.

Resumo Objetivo Avaliar a acurácia diagnóstica do antígeno de câncer 125 (cancer antigen 125, CA125, em inglês) e dos parâmetros do hemograma como as razões neutrófilo/linfócito (RNL), plaqueta/linfócito (RPL), e trombocitose em pacientes com massas ovarianas. Métodos Este é um estudo retrospectivo realizado em um hospital terciário no período de janeiro de 2010 a novembro de 2016. Foram incluídas de forma consecutiva mulheres encaminhadas por massas anexiais suspeitas. Foram dosados hemogramas e CA125 no soro de 528 mulheres com massas ovarianas antes da cirurgia ou biópsia. Foram avaliados os desempenhos diagnósticos da RNL, da RPL, das plaquetas (PLQs) e do CA125, considerando-os isoladamente e associados entre si. Testamos a utilidade clínica dos parâmetros do hemograma e do CA125 na discriminação das massas ovarianas por análise de curva de decisão (ACD). Resultados Os melhores equilíbrios entre sensibilidade e especificidade foram obtidos por meio das associações do CA125 ou PLQs ≥ 350/nL, com 70,14% e 71,66%, CA125 ou PLQs ≥ 400/nL, com 67,30% e 81,79%, CA125 ou RPL, com76,3% e 64,87%, e CA125 ou RNL, com 71,09% e 73,89%, respectivamente. Conclusão Na ACD, nenhum parâmetro do hemograma isolado se mostrou superior ao CA125 na predição de malignidade de tumores ovarianos no pré-operatório.

Laboratory predictors of survival in ovarian cancer

SUMMARY OBJECTIVE To relate disease-free survival and overall survival with type I and type II ovarian cancer and preoperative laboratory parameters biomarkers. METHODS A retrospective study was carried out based on the collection of data from medical records of patients with ovarian tumors. Kaplan-Mayer curves were drawn based on the statistical analysis of the data and were compared using the Log-rank test. RESULTS Disease-free survival in type I ovarian cancer was significantly higher than in type II (p=0.0013), as well as in those with normal levels of CA-125 (p=0.0243) and with a platelet-lymphocyte ratio (PLR) lower than 200 (p=0.0038). The overall survival of patients with type I ovarian cancer was significantly higher than in patients with type II, as well as in patients with normal CA-125 serum levels (p=0.0039) and those with a preoperative fasting glucose of less than 100 mg/dL. CONCLUSION CA-125 levels may predict greater overall and disease-free survival. PLR < 200 may suggest greater disease-free survival, whereas normal fasting glucose may suggest greater overall survival.

RESUMO OBJETIVO Relacionar a sobrevida livre de doença e sobrevida global com câncer de ovário tipos I e II, assim como com parâmetros laboratoriais pré-operatórios biomarcadores. MÉTODOS Estudo retrospectivo realizado com base na coleta de dados de prontuários de pacientes com tumor ovariano. As curvas de Kaplan-Mayer foram realizadas em relação à análise estatística dos dados, sendo comparadas pelo teste de Log-rank. RESULTADOS A sobrevida livre de doença nas pacientes com câncer de ovário tipo I foi significativamente maior do que nas pacientes com câncer de ovário tipo II (p = 0,0013), bem como maior naquelas com níveis normais de CA-125 (p = 0,0243) e com relação plaquetas-linfócitos (RPL) inferior a 200 (p = 0,0038). A sobrevida global de pacientes com câncer de ovário tipo I foi significativamente maior do que em pacientes com tipo II, maior em pacientes com níveis séricos normais de CA-125 (p = 0,0039) e naquelas com glicemia de jejum pré-operatória menor que 100 mg / dL. CONCLUSÃO Os níveis de CA-125 podem predizer uma sobrevida global e livre de doença. A RPL < 200 pode sugerir uma maior sobrevida livre de doença, enquanto uma glicemia normal de jejum, uma maior sobrevida global.

Primary Malignant Mesothelioma of the Peritoneum Mistaken for Peritoneal Tuberculosis due to Elevated Cancer Antigen 125 / 대한소화기학회지

A differential diagnosis of ascites is always challenging for physicians. Peritoneal tuberculosis is particularly difficult to distinguish from peritoneal carcinomatosis because of the similarities in clinical manifestations and laboratory results. Although the definitive diagnostic method for ascites is to take a biopsy of the involved tissues through laparoscopy or laparotomy, there are many limitations in performing biopsies in clinical practice. For this reason, physicians have attempted to find surrogate markers that can substitute for a biopsy as a confirmative diagnostic method for ascites. CA 125, which is known as a tumor marker for gynecological malignancies, has been reported to be a biochemical indicator for peritoneal tuberculosis. On the other hand, the sensitivity of serum CA 125 is low, and CA 125 may be elevated due to other benign or malignant conditions. This paper reports the case of a 66-year-old male who had a moderate amount of ascites and complained of dyspepsia and a febrile sensation. His abdominal CT scans revealed a conglomerated mass, diffuse omental infiltration, and peritoneal wall thickening. Initially, peritoneal tuberculosis was suspected due to the clinical symptoms, CT findings, and high serum CA 125 levels, but non-specific malignant cells were detected on cytology of the ascitic fluid. Finally, he was diagnosed with primary malignant peritoneal mesothelioma after undergoing a laparoscopic biopsy.

Prediction of survival outcomes in patients with epithelial ovarian cancer using machine learning methods / 부인종양

OBJECTIVES: The aim of this study was to develop a new prognostic classification for epithelial ovarian cancer (EOC) patients using gradient boosting (GB) and to compare the accuracy of the prognostic model with the conventional statistical method. METHODS: Information of EOC patients from Samsung Medical Center (training cohort, n=1,128) was analyzed to optimize the prognostic model using GB. The performance of the final model was externally validated with patient information from Asan Medical Center (validation cohort, n=229). The area under the curve (AUC) by the GB model was compared to that of the conventional Cox proportional hazard regression analysis (CoxPHR) model. RESULTS: In the training cohort, the AUC of the GB model for predicting second year overall survival (OS), with the highest target value, was 0.830 (95% confidence interval [CI]=0.802–0.853). In the validation cohort, the GB model also showed high AUC of 0.843 (95% CI=0.833–0.853). In comparison, the conventional CoxPHR method showed lower AUC (0.668 (95% CI=0.617–0.719) for the training cohort and 0.597 (95% CI=0.474–0.719) for the validation cohort) compared to GB. New classification according to survival probability scores of the GB model identified four distinct prognostic subgroups that showed more discriminately classified prediction than the International Federation of Gynecology and Obstetrics staging system. CONCLUSION: Our novel GB-guided classification accurately identified the prognostic subgroups of patients with EOC and showed higher accuracy than the conventional method. This approach would be useful for accurate estimation of individual outcomes of EOC patients.

PARAGON (ANZGOG-0903): a phase 2 study of anastrozole in asymptomatic patients with estrogen and progesterone receptor-positive recurrent ovarian cancer and CA125 progression / 부인종양

OBJECTIVE: A subset of patients with recurrent ovarian cancer (ROC) may benefit from antiestrogen therapy with higher response rates reported in tumors that are strongly estrogen receptor (ER)-positive (ER+). PARAGON is a basket trial that incorporates 7 phase 2 trials investigating the activity of anastrozole in patients with ER+ and/or progesterone receptor (PR)-positive (PR+) recurrent/metastatic gynecological cancers. METHODS: Postmenopausal women with ER+ and/or PR+ ROC, who were asymptomatic and had cancer antigen 125 (CA125) progression after response to first line chemotherapy, where chemotherapy was not clinically indicated. Patients received anastrozole 1 mg daily until progression or unacceptable toxicity. RESULTS: Fifty-four patients were enrolled (52 evaluable). Clinical benefit at three months (primary endpoint) was observed in 18 patients (34.6%; 95% confidence interval [CI]=23%–48%). Median progression-free survival (PFS) was 2.7 months (95% CI=2.1–3.1). The median duration of clinical benefit was 6.5 months (95% CI=2.8–11.7). Most patients progressed within 6 months of starting anastrozole but 12 (22%) continued treatment for longer than 6 months. Anastrozole was well tolerated. In the exploratory analysis, ER histoscores and the intensity of ER staining did not correlate with clinical benefit rate or PFS. CONCLUSION: A subset of asymptomatic patients with ER+ and/or PR+ ROC and CA125 progression had durable clinical benefit on anastrozole, with acceptable toxicity. Anastrozole may delay symptomatic progression and the time to subsequent chemotherapy. The future challenge is to identify the subset of patients most likely to benefit from an aromatase inhibitor and whether the clinical benefit could be increased by the addition of other agents.

Treatment strategies for patients with advanced ovarian cancer undergoing neoadjuvant chemotherapy: interval debulking surgery or additional chemotherapy? / 부인종양

OBJECTIVE: To treat advanced ovarian cancer, interval debulking surgery (IDS) is performed after 3 cycles each of neoadjuvant chemotherapy (NAC) and postoperative chemotherapy (IDS group). If we expect that complete resection cannot be achieved by IDS, debulking surgery is performed after administering additional 3 cycles of chemotherapy without postoperative chemotherapy (Add-C group). We evaluated the survival outcomes of the Add-C group and determined their serum cancer antigen 125 (CA125) levels to predict complete surgery. METHODS: A retrospective chart review of all stage III and IV ovarian, fallopian tube, and peritoneal cancer patients treated with NAC in 2007–2016 was conducted. RESULTS: About 117 patients comprised the IDS group and 26 comprised the Add-C group. Univariate and multivariate analyses revealed that Add-C group had an equivalent effect on progression-free survival (PFS; p=0.09) and overall survival (OS; p=0.94) compared with the IDS group. Multivariate analysis revealed that patients who developed residual disease after surgery had worse PFS (hazard ratio [HR]=2.18; 95% confidence interval [CI]=1.45–3.28) and OS (HR=2.33; 95% CI=1.43–3.79), and those who received <6 cycles of chemotherapy had worse PFS (HR=5.30; 95% CI=2.56–10.99) and OS (HR=3.05; 95% CI=1.46–6.38). The preoperative serum CA125 cutoff level was 30 U/mL based on Youden index method. CONCLUSIONS: Administering 3 additional cycles of chemotherapy followed by debulking surgery exhibited equivalent effects on survival as IDS followed by 3 cycles of postoperative chemotherapy. Preoperative serum CA125 levels of ≤30 U/mL may be a useful predictor of achieving complete surgery.

Improved preoperative risk stratification with CA-125 in low-grade endometrial cancer: a multicenter prospective cohort study / 부인종양

OBJECTIVES: The global obesity epidemic has great impact on the prevalence of low-grade endometrial carcinoma. The preoperative tumor serum marker cancer antigen 125 (CA-125) might contribute to improved identification of high-risk patients within this group. The study aimed to investigate the prognostic value of CA-125 in relation to established preoperative prognosticators, with a focus on identifying patients with poor outcome in low-grade endometrial carcinoma (EC) patients. METHODS: Prospective multicenter cohort study including all consecutive patients surgically treated for endometrial carcinoma in nine collaborating hospitals from September 2011 until December 2013. All preoperative histopathological diagnoses were reviewed in a blinded manner. Associations between CA-125 and clinicopathological features were determined. Univariable and multivariable analysis by Cox regression were used. Separate analyses were performed for preoperatively designated low-grade and high-grade endometrial carcinoma patients. RESULTS: A total of 333 patients were analyzed. CA-125 was associated with poor prognostic features including advanced International Federation of Gynecology and Obstetrics (FIGO) stage. In multivariable analysis, age, preoperative tumor and CA-125 were significantly associated with disease-free survival (DFS); preoperative grade, tumor type, FIGO and CA-125 were significantly associated with disease-specific survival (DSS). Low-grade EC patients with elevated CA-125 revealed a DFS of 80.6% and DSS of 87.1%, compared to 92.1% and 97.2% in low-grade EC patients with normal CA-125. CONCLUSION: Preoperative elevated CA-125 was associated with poor prognostic features and independently associated with DFS and DSS. Particularly patients with low-grade EC and elevated CA-125 represent a group with poor outcome and should be considered as high-risk endometrial carcinoma.

Involved-field radiation therapy for selected cases of recurrent ovarian cancer / 부인종양

OBJECTIVES: In our institutional experience, involved-field radiation therapy (IFRT) yields favorable outcomes in patients with recurrent epithelial ovarian cancer (EOC). This retrospective study aimed to investigate the clinical benefits of IFRT in this patient population. METHODS: Among patients treated with IFRT for recurrent EOC between 2010 and 2017, 61 patients with 90 treatments were included. IFRT encompassed all treatable lesions identified via imaging studies with 10–15-mm margins. Prescribed doses were ≥45 Gy (equivalent dose in 2 Gy/fraction). RESULTS: Patients were followed up for a median of 19.0 (Interquartile range, 8.6–34.9) months after IFRT. The 2-year in-field control, progression-free survival, and overall survival (OS) rates were 42.7%, 24.2%, and 78.9%, respectively. Fifty-three IFRT sessions (58.9%) were followed by systemic chemotherapy, and the median chemotherapy-free interval (CFI) was 10.5 (95% confidence interval=7.3–13.7) months. A higher carbohydrate antigen-125 (CA-125) level correlated with a worse 2-year OS (69.2% vs. 91.0%; p=0.001) and shorter median CFI (4.7 vs. 11.9 months; p12 months. For patients with a normal CA-125 level and/or platinum-sensitive tumor, IFRT prolonged CFI regardless of pre-existing carcinomatosis, gross tumor volume, and number of treatment sites. CONCLUSION: Our early experience demonstrates the safety and feasibility of IFRT as an effective salvage therapy and enables a “chemotherapy holiday” in selected recurrent EOC settings. The CA-125 value before IFRT (within normal range) and/or platinum sensitivity could be used as selection criteria for IFRT.