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The association between endometrial cancer and the BRCA1 and BRCA2 genes is not fully understood, and the risk elevation of endometrial cancer in patients with hereditary breast and ovarian cancer (HBOC) is not understood. The present report examines a rare case of HBOC syndrome and an uncharacterized variant of the BRCA1 gene in a patient diagnosed with endometrial cancer. A 46-year-old woman, gravida 1 para 1, was referred to Wakayama Medical University Hospital (Wakayama, Japan) because positron emission tomography/computed tomography (PET/CT) showed a high FDG uptake in the corpus uteri and the left ovary. PET/CT was performed just after mastectomy for left-sided breast cancer (triple negative). The patient had previously undergone partial mastectomy for right-sided breast cancer (triple negative) and was treated with radiation therapy to the right residual breast when she was 39 years old. Laparoscopic hysterectomy and bilateral adnexectomy were performed, and the histological diagnosis was endometrioid carcinoma, grade 1. Her germline BRCA status was tested by blood examination and the result was 'NM_007294.4(BRCA1):c.49G>C (p.Ala17Pro)'. The variant was evaluated as 'likely pathogenic'. The patient was diagnosed with HBOC syndrome and endometrial cancer, pT1ANxM0. The patient had no recurrence of breast or endometrial cancer 16 months after gynecologic surgery.
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BACKGROUND: The goal of this study is to assess the oncologic outcomes of elderly patients who underwent hysterectomy for endometrial cancer across three variables: hysterectomy approach, lymph node resection, and adjuvant therapy. METHODS: Hospital records of patients aged ≥ 70 years who underwent hysterectomy for endometrial cancer were obtained from 19 institutions. Patients were categorized into three risk groups: low, intermediate, and high. In each group, disease-free survival and overall survival were compared according to hysterectomy approach, lymph node resection, and adjuvant therapy using Kaplan-Meier method. Cox regression analysis with a 95% confidence interval was performed to estimate relative risk (RR) of death. RESULTS: A total of 1246 patients were included. In the low-risk group, the adjusted RR for death for minimally invasive surgery (MIS) versus laparotomy and lymph node resection versus no lymph node resection were 0.64 (0.24-1.72) and 0.52 (0.24-1.12), respectively. In the intermediate-risk group, the adjusted RR for death for MIS versus laparotomy, lymph node resection versus no lymph node resection, and adjuvant therapy versus no adjuvant therapy were 0.80 (0.36-1.77), 0.60 (0.37-0.98), and 0.89 (0.55-1.46), respectively. In the high-risk group, the adjusted RRs for death for lymph node resection versus no lymph node resection and adjuvant therapy versus no adjuvant therapy were 0.56 (0.37-0.86) and 0.60 (0.38-0.96), respectively. CONCLUSIONS: MIS is not inferior to laparotomy in uterine-confined diseases. Lymph node resection improved the outcome for all disease stages and histological types. In contrast, adjuvant therapy improved the outcomes only in high-risk patients.
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Neoplasias Endometriales , Histerectomía , Anciano , Neoplasias Endometriales/patología , Femenino , Humanos , Histerectomía/métodos , Japón , Escisión del Ganglio Linfático/métodos , Estadificación de Neoplasias , Estudios RetrospectivosRESUMEN
Retained products of conception (RPOC) is a complication that occurs in the second trimester of pregnancy. We enrolled 98 women who had a miscarriage or termination with gemeprost in the second trimester of pregnancy. Eighteen cases (18.4%) were RPOC-positive. The gestational week at miscarriage or termination was earlier in the RPOC-positive group than those in the RPOC-negative group (p = .003). The period of the third stage of labour was longer in the RPOC-positive group than in RPOC-negative group (p = .040). The proportion of placental forceps use was higher in the RPOC-positive group than in RPOC-negative group (p = .003). Multivariate logistic regression analysis showed that gestational week (OR: 3.53; p = .04) and use of placental forceps at delivery (OR: 2.21; p = .012) were independent risk factors for RPOC. Earlier gestational weeks at miscarriage or termination and use of placental forceps at delivery were predictive factors for RPOC after second trimester miscarriage or termination with gemeprost.Impact StatementWhat is already known on this subject? There have been some reports on risk factors of RPOC. A previous report showed that the termination of pregnancy with misoprostol at earlier periods was associated with an increased risk of RPOC.What the results of this study add? There have been few studies on the risk factors of RPOC after miscarriage or termination with gemeprost. In this study, we evaluated the risk factors of RPOC after miscarriage or termination of pregnancy with gemeprost in the second trimester. We found that an earlier gestational age (between 12 and 17 weeks) at delivery and using placental forceps to remove placenta were significant risk factors of RPOC after miscarriage or termination of pregnancy with gemeprost in the second trimester.What the implications are of these findings for clinical practice and/or further research? An earlier gestational age and using forceps to remove placenta may be significant risk factors for RPOC. The accurate evaluation and treatment for RPOC is important for maternal life-saving efforts and subsequent pregnancies. Further research is needed to draft a standardised protocol for RPOC.
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Abortivos no Esteroideos , Aborto Inducido , Aborto Espontáneo , Abortivos no Esteroideos/efectos adversos , Aborto Inducido/efectos adversos , Aborto Espontáneo/etiología , Alprostadil/análogos & derivados , Femenino , Humanos , Lactante , Japón , Placenta , Embarazo , Segundo Trimestre del Embarazo , Estudios Retrospectivos , Factores de RiesgoRESUMEN
Low-grade endometrial stromal sarcoma (LG-ESS) is a rare tumor that mostly occurs in perimenopausal women. Treatment with total hysterectomy and bilateral salpingo-oophorectomy is recommended, although fertility preservation or ovarian preservation may be considered in younger patients. The present study reports a case of LG-ESS in a young woman diagnosed after resection of endometrial polyp-like lesions. A 26-year-old nulligravid woman was referred to our hospital after being diagnosed with endometrial polyps. Hysteroscopic endometrial polypectomy was performed twice, and LG-ESS was suspected on postoperative pathological examination. Magnetic resonance imaging revealed a tumor 5-cm in diameter on the right side of the uterus. In light of the young age of the patient, tumorectomy was first performed, and postoperative pathological diagnosis was LG-ESS with the positive resection margin. After thorough discussion with the patient about fertility preservation and recurrence risk, a total abdominal hysterectomy and ovarian preservation was performed. Medroxyprogesterone therapy was performed postoperatively and no recurrence was observed for 2 years.
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There have been very few reports on the use of immune checkpoint inhibitors for malignant tumors during pregnancy. Herein, the current study reports a case of a patient diagnosed with advanced malignant melanoma who was treated with pembrolizumab during pregnancy. A 40-year-old primigravida underwent noninvasive prenatal testing at 10 weeks of gestation, and the result was inconclusive, suggesting the possibility of maternal malignancy. A biopsy of the gluteal mass led to a diagnosis of malignant melanoma, and computed tomography revealed extensive metastases in her lungs and lymph nodes. She had a strong desire to proceed with pregnancy. In consideration of fetal growth and maturation, monotherapy was administered with pembrolizumab from 21 weeks of gestation, aiming for 28 weeks of gestation. The fetus grew well without maternal complications. At 28 weeks of pregnancy, the patient gave birth to a healthy boy by cesarean section. There was no evidence of metastasis in the placenta. The patient received nivolumab-ipilimumab combination therapy from postpartum day 13, followed by nivolumab monotherapy, and has been alive with controlled disease for 20 months.
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Obstructed hemivagina and ipsilateral renal anomaly (OHVIRA) syndrome is a rare Mullerian duct anomaly. Cases with pelvic inflammatory disease or endometriosis have been reported, which may influence fertility or the quality of life of patients; therefore, an accurate and early diagnosis is essential. The present study reports the case of patient (25-year-old female, gravida 0 para 0) with OHVIRA syndrome. Magnetic resonance imaging and a computed tomography scan revealed uterus didelphys and right renal agenesis. An opening was found on the vaginal septum during the menstrual period. Upon diagnostic vaginoscopy and hysteroscopy through the opening, the right vaginal cavity was enclosed, and the right uterine cervix and cavity were normal. The patient was diagnosed with OHVIRA syndrome. Her vaginal septum was surgically removed under direct visualization and the pathological findings of the resected septum revealed a benign squamous epithelium. The post-operative course was uneventful and restenosis of the vagina was not observed. On the whole, the present study demonstrates that the technique, diagnostic vaginoscopy and hysteroscopy, is minimally invasive and is sufficient for the diagnosis of incomplete vaginal obstruction-type OHVIRA syndrome.
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BACKGROUND: The development of perforations or fistulas in the Gastrointestinal (GI) tract or genitourinary (GU) system is a serious adverse effect of bevacizumab. The aim of this study was to investigate the incidences of these GI/GU events as well as their association with previous radiotherapy (RT) in Japanese women with cervical cancer. METHODS: We conducted a written questionnaire survey among 14 gynecological institutions belonging to the Oncology Research Committee of the Obstetrical and Gynecological Society of Kinki District, Japan. The severity of GI/GU events was classified according to the National Cancer Institute's Common Terminology Criteria for Adverse Events version 5.0. All data were extracted from survey responses and maintained in an Excel spreadsheet and summarized using descriptive statistics. RESULTS: The information of 224 Japanese women with cervical cancer (152 recurrent and 72 advanced) who were treated with bevacizumab-containing chemotherapy was collected from 14 institutions. Of these, 65% had been previously treated with RT. GI/GU events of any grade developed in 25 (11.2%) patients, leading directly to death in 3 (1.3%) patients. When compared, the incidence of GI/GU events was higher in recurrent disease patients than in advanced disease patients (13.8% vs 5.6%, p = 0.0728). When examined according to the history of RT, the incidence of GI/GU events was greater in patients with a history of RT than in those without (14.5% vs 5.1%, p = 0.044). CONCLUSION: More than 10% of patients experience GI/GU events during or after receiving bevacizumab-containing chemotherapies. Prior RT is a risk factor for bevacizumab-associated GI/GU events.
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Neoplasias de la Próstata , Neoplasias del Cuello Uterino , Bevacizumab/efectos adversos , Femenino , Humanos , Japón/epidemiología , Masculino , Encuestas y Cuestionarios , Neoplasias del Cuello Uterino/tratamiento farmacológico , Neoplasias del Cuello Uterino/epidemiologíaRESUMEN
Castleman's disease is a rare benign disorder of unknown etiology characterized by proliferation of lymphoid tissues. Castleman's disease arising from pelvic retroperitoneum is clinically rare. The present case report describes a rare case of laparoscopically resected Castleman's disease in the pelvic retroperitoneum associated with benign ovarian cyst. A 47-year-old woman, gravida 5, para 3, was referred to to the Department of Obstetrics and Gynecology of Wakayama Medical University with a suspected pelvic tumor. Magnetic resonance imaging revealed that the solid tumor was localized in the retroperitoneal space at the right side of the pelvis. The patient underwent laparoscopic surgery for the resection of the pelvic retroperitoneal tumor, with complete tumor resection. Postoperative pathological examination established the diagnosis of Castleman's disease. The postoperative course was uneventful, with no evidence of local recurrence or systemic disease 6 months after diagnosis.
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The aim of the present study was to clarify the feasibility and efficacy of helical tomotherapy during concurrent chemoradiotherapy for treating cervical cancer. The medical records of 13 patients who underwent oncurrent chemoradiotherapy using helical tomotherapy for cervical cancer at Wakayama Medical University Hospital between 2013 and 2015 were retrospectively reviewed. A total of 15 patients who underwent oncurrent chemoradiotherapy using conventional radiotherapy (CRT) between 2008 and 2013 at our institution were also examined for comparison. The median age of patients treated with helical tomotherapy was 60 (range, 35-71), and the median age of patients treated with CRT was 57 (range, 43-77). The median follow-up period was 27 months (range, 3-46) in the tomotherapy group and 35 months (range, 7-88) in the CRT group. The frequency of G3/4 thrombocytopenia in the tomotherapy group was significantly higher than that in the CRT group (P=0.049). However, the platelet count spontaneously recovered without transfusion. There were no significant differences between the groups in terms of frequency of G3/4 neutropenia, diarrhea or late intestine injury. The rate of complete response in the tomotherapy group and the CRT group was 84.6 and 73.3%, respectively, and there was no significant difference in the response rate between the groups. There were no significant differences in the progression-free survival or progression-free rate in the irradiation field between the groups. Adverse events from concurrent chemoradiotherapy using helical tomotherapy were acceptable and clinically controllable. The present results suggest that helical tomotherapy is efficient during concurrent chemoradiotherapy for treatment of advanced cervical cancer.
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Large-cell neuroendocrine carcinoma (LCNEC) is a high-grade neuroendocrine tumor. LCNECs arising from the genital organs are highly malignant and rare, with <20 cases of LCNEC developing from the uterine endometrium reported to date. We herein present the case of a patient with LCNEC of the endometrium. The patient was a 52-year-old woman, who exhibited lower abdominal pain and rapid uterine enlargement during outpatient treatment for uterine myoma. The endometrial biopsy suggested a diagnosis of poorly differentiated carcinoma or carcinosarcoma. Based on magnetic resonance imaging and positron emission tomography/computed tomography, endometrial stromal sarcoma was suspected. The serum lactate dehydrogenase level was abnormally high. Due to the suspicion of stage IIIC malignant tumor of the uterine corpus, surgery was performed. The pathological diagnosis was stage IIIC2 LCNEC of the endometrium. Recurrence occurred in the vaginal stump, and concurrent chemoradiotherapy (CCRT) was initiated 1 month after the surgery. The residual lesions markedly shrank, but metastasis to the upper abdominal region and cervix subsequently developed. CCRT was attempted, but the associated adverse effects were severe and was switched to palliative treatment. The patient eventually succumbed to the disease 309 days after surgery.
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Mature cystic teratomas are the most common among all ovarian neoplasms, representing 30-40% of the cases. However, to the best of our knowledge, there have been only two reports of mature cystic teratomas occurring in identical twins to date. We herein report a case of identical twins with mature cystic teratomas who were treated with laparoscopic surgery. A 32-year-old woman was referred to our hospital due to a tumor in the right ovary. The patient underwent laparoscopic resection of the ovarian tumor and the pathological diagnosis was benign mature cystic teratoma. Two years later, the identical twin of the abovementioned patient was referred to our hospital also due to a right ovarian tumor. The patient underwent laparoscopic resection of the ovarian tumor and the pathological diagnosis was benign mature cystic teratoma. Therefore, for early diagnosis, it may be important to consider the possibility of mature cystic teratoma in the identical twin of a patient, even in the absence of symptoms.
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Malignant melanoma (MM) in the female genital tract accounts for less than 2% of all melanomas, and the vast majority associated occur in the vulva and vagina. Primary MM of the uterine cervix is extremely rare and its prognosis is very poor. We report a case of primary MM of the cervix with dissemination throughout the vaginal wall. A 66-year-old woman presented with postmenopausal bleeding. Gynecologic examination demonstrated a 2 cm polypoid blackish-pigmented tumor on the cervix with multiple small blackish-pigmented lesions throughout the vaginal wall. Cervical Pap smear cytology showed malignant melanoma. MRI and PET/CT did not detect any distant or lymph node metastases. She underwent radical hysterectomy, pelvic lymphadenectomy, and total vaginectomy. The pathological diagnosis was FIGO stage IIIA primary cervical MM. She received adjuvant chemotherapy with 6 courses of dacarbazine, but 6 months later, multiple lung metastases were detected. Despite 4 courses of anti-PD-1 antibody (nivolumab) treatment, she died of the disease 13 months after surgery.
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Pyomyoma is a rare complication, which withoug antibiotics or surgical intervention, may cause sepsis and mortality. The present study reported a case of large uterine pyomyoma in a perimenopausal female. A 53-year-old multigravida woman was referred to the Department of Obstetrics and Gynecology (Wakayama Medical University, Wakayama, Japan) due to progressive abdominal distension. The patient presented with anemia gravis, severe inflammatory reaction and cachexia. Computed tomography revealed a large unilocular mass, 50 cm in size, with an irregular surface and thickened wall, occupying the entire abdomen. Following antibiotic medication, the patient underwent a total abdominal hysterectomy and bilateral salpingo-oophorectomy. Intraoperative findings demonstrated a solid tumor arising from the back of the uterine body. A total of 12 liters of purulent, malodorous fluid was drained from the tumor. The resected mass was 50 cm in size and 13.5 kg in weight. Cultures of the pus revealed the presence of Streptococcus agalactiae. Pathological findings revealed suppurative leiomyoma with no malignancy. Large pyomyoma is difficult to distinguish from a gynecological malignant tumor types, particularly in perimenopausal women with non-specific clinical presentation. Although pyomyoma is a benign tumor, care must be taken to discriminate these from large abdominal tumors.
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The objective of the present study was to investigate the usefulness of the maximum standardized uptake value (SUVmax) of the primary tumor on preoperative 18F-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography and computed tomography (PET/CT) as a prognostic indicator in patients with endometrial neoplasms. A total of 75 patients with endometrial cancer or uterine carcinosarcoma who underwent surgical treatment were included in the present study. All patients underwent preoperative PET/CT, and the correlation between the SUVmax of the primary tumor and clinical outcomes was analyzed. The SUVmax was significantly higher in patients with stage II/III disease, a histology of grade 3 endometrioid adenocarcinoma and carcinosarcoma, a positive lymph node (LN) status, positive lymph-vascular space involvement (LVSI), and deep (≥1/2) myometrial invasion. Receiver operating characteristic curve analysis revealed that the optimal cut-off values of SUVmax for predicting a positive LN, LVSI and deep myometrial invasion were 7.49, 6.45 and 6.45, respectively. The overall survival (OS) and progression-free survival (PFS) of patients with a high SUVmax were significantly lower compared with those of patients with a low SUVmax using the cut-off value of 7.30. However, no significant difference was observed in the OS or PFS between the high and low SUVmax groups when analyzed in carcinosarcoma patients alone. Finally, multivariate analyses demonstrated that the SUVmax of the primary tumor was an independent prognostic factor for impaired PFS in 55 endometrioid adenocarcinoma patients; however, not in all patients, including those with carcinosarcoma. The present findings demonstrated that the SUVmax of the primary tumor may be a useful biomarker for predicting clinical outcomes of patients with endometrial cancer, although its prognostic impact appears to be limited in patients with uterine carcinosarcoma.
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The objective of the present study was to investigate the prognostic value of 18F-fluoro-2-deoxy-D-glucose (FDG) uptake by primary tumors on positron emission tomography/computed tomography (PET/CT) in surgically resectable cervical cancer. A total of 59 patients with stage IA2-IIB cervical cancer who underwent preoperative FDG-PET/CT, followed by radical hysterectomy and lymphadenectomy, were included in the study. The maximum standardized uptake value (SUVmax) of the primary tumor was measured, and the association between the SUVmax and clinicopathological factors or patient outcomes was analyzed. The SUVmax was significantly higher in patients with an advanced stage, lymph node metastasis, lymph-vascular space involvement and large tumors. The overall survival (OS) and progression-free survival (PFS) of patients with a high SUVmax were significantly lower compared with patients with a low SUVmax, using an optimal cut-off value of 7.36 for OS and 5.59 for PFS obtained from receiver operating characteristic curve analysis. Similarly, OS and PFS in patients with a high SUVmax were significantly lower in 39 patients with stage IB using a cut-off value of 7.90 and 6.69 for OS and PFS, respectively. Finally, multivariate analyses showed that the SUVmax of the primary tumor was an independent prognostic factor for impaired PFS in all patients and those with stage IB alone. These findings demonstrated that a high SUVmax on preoperative PET/CT was correlated with unfavorable clinical outcomes in patients receiving radical hysterectomy, suggesting that the SUVmax of the primary tumor may be a prognostic indicator for surgically-treated, early-stage invasive cervical cancer.
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OBJECTIVE: The aim of this study was to clarify the clinicopathologic factors of stages IB to IIB cervical adenocarcinoma. METHODS: Several clinicopathologic factors were compared between 35 patients who underwent radical hysterectomy and pelvic lymphadenectomy due to cervical adenocarcinoma stages IB to IIB and 77 patients with squamous cell carcinoma (SCC). RESULTS: In patients with adenocarcinoma, univariate analysis demonstrated that International Federation of Gynecology and Obstetrics stage, tumor size, and lymphovascular space invasion were significantly associated with progression-free survival (PFS), whereas FIGO stage, lymphovascular space invasion, and lymph node metastasis were significantly associated with overall survival (OS). However, multivariate analysis revealed that FIGO stage was the only significant factor for PFS in patients with adenocarcinoma. In patients with SCC, univariate analysis demonstrated that FIGO stage and lymph node metastasis were significantly associated with PFS, whereas FIGO stage, lymphovascular space invasion, and lymph node metastasis were significantly associated with OS. Multivariate analysis revealed that lymph node metastasis was the only significant factor for PFS and OS in patients with SCC. In 26 patients who were positive for high-risk human papillomavirus (HPV), including both adenocarcinoma and SCC patients, univariate and multivariate analyses revealed that HPV18 was significantly associated with poorer PFS compared with non-HPV18. There was a significant difference in distribution of HPV genotype between adenocarcinoma and SCC. CONCLUSIONS: Careful treatment may be necessary for the patients with lymphovascular space invasion in early-stage cervical adenocarcinoma. The presence of HPV18 may have an influence on the prognosis of early-stage cervical carcinoma.
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Adenocarcinoma/patología , Carcinoma de Células Escamosas/patología , Escisión del Ganglio Linfático , Infecciones por Papillomavirus/complicaciones , Neoplasias del Cuello Uterino/patología , Adenocarcinoma/complicaciones , Adenocarcinoma/terapia , Adulto , Anciano , Vasos Sanguíneos/patología , Carcinoma de Células Escamosas/complicaciones , Carcinoma de Células Escamosas/terapia , Quimioterapia Adyuvante , Supervivencia sin Enfermedad , Femenino , Genotipo , Papillomavirus Humano 18/genética , Humanos , Histerectomía , Metástasis Linfática , Vasos Linfáticos/patología , Persona de Mediana Edad , Invasividad Neoplásica , Estadificación de Neoplasias , Infecciones por Papillomavirus/virología , Radioterapia Adyuvante , Tasa de Supervivencia , Carga Tumoral , Neoplasias del Cuello Uterino/complicaciones , Neoplasias del Cuello Uterino/terapiaRESUMEN
Vaginal carcinoma is a rare gynecological malignancy that is usually treated by radiation therapy and/or surgery combined with chemotherapy. Here, we report a case of invasive vaginal carcinoma in a young woman who underwent fertility-sparing treatment involving neoadjuvant chemotherapy and conservative surgery. A 36-year-old non-parous woman had a solid tumor in the vagina. Positron emission tomography/computed tomography showed a tumor in the vagina with high FDG uptake (SUV = 17.33) but no metastatic lesions. The patient was diagnosed with vaginal squamous cell carcinoma, FIGO stage I, T1N0M0. Because she wished to retain her fertility, neoadjuvant chemotherapy consisting of irinotecan hydrochloride and nedaplatin was initiated. After four courses of chemotherapy, partial vaginectomy was carried out and the pathological diagnosis of the residual lesion was VAIN 3. Following two further courses of the same chemotherapy, she obtained complete response, and has shown no evidence of disease for 14 months.
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Carcinoma de Células Escamosas/cirugía , Tratamientos Conservadores del Órgano , Vagina/cirugía , Neoplasias Vaginales/cirugía , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica , Camptotecina/análogos & derivados , Camptotecina/uso terapéutico , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/fisiopatología , Femenino , Humanos , Irinotecán , Terapia Neoadyuvante , Estadificación de Neoplasias , Compuestos Organoplatinos/uso terapéutico , Inducción de Remisión , Hemorragia Uterina/etiología , Hemorragia Uterina/prevención & control , Vagina/efectos de los fármacos , Vagina/patología , Neoplasias Vaginales/tratamiento farmacológico , Neoplasias Vaginales/patología , Neoplasias Vaginales/fisiopatologíaRESUMEN
Indoleamine 2,3-dioxygenase (IDO) is a tryptophan-catabolizing enzyme that has immunoregulatory functions. Our prior study showed that tumoral IDO overexpression is involved in disease progression and impaired patient survival in human ovarian cancer, although its mechanism remains unclear. The purpose of the present study is to clarify the role of IDO during the process of peritoneal dissemination of ovarian cancer. Indoleamine 2,3-dioxygenase cDNA was transfected into the murine ovarian carcinoma cell line OV2944-HM-1, establishing stable clones of IDO-overexpressing cells (HM-1-IDO). Then HM-1-IDO or control vector-transfected cells (HM-1-mock) were i.p. transplanted into syngeneic immunocompetent mice. The HM-1-IDO-transplanted mice showed significantly shortened survival compared with HM-1-mock-transplanted (control) mice. On days 11 and 14 following transplantation, the tumor weight of peritoneal dissemination and ascites volume were significantly increased in HM-1-IDO-transplanted mice compared with those of control mice. This tumor-progressive effect was coincident with significantly reduced numbers of CD8(+) T cells and natural killer cells within tumors as well as increased levels of transforming growth factor-ß and interleukin-10 in ascites. Finally, treatment with the IDO inhibitor 1-methyl-tryptophan significantly suppressed tumor dissemination and ascites with reduced transforming growth factor-ß secretion. These findings showed that tumor-derived IDO promotes the peritoneal dissemination of ovarian cancer through suppression of tumor-infiltrating effector T cell and natural killer cell recruitment and reciprocal enhancement of immunosuppressive cytokines in ascites, creating an immunotolerogenic environment within the peritoneal cavity. Therefore, IDO may be a promising molecular target for the therapeutic strategy of ovarian cancer.
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Indolamina-Pirrol 2,3,-Dioxigenasa/metabolismo , Invasividad Neoplásica/inmunología , Neoplasias Ováricas/patología , Neoplasias Peritoneales/secundario , Escape del Tumor/inmunología , Animales , Western Blotting , Línea Celular Tumoral , Cromatografía Líquida de Alta Presión , Ensayo de Inmunoadsorción Enzimática , Femenino , Inmunohistoquímica , Indolamina-Pirrol 2,3,-Dioxigenasa/inmunología , Linfocitos Infiltrantes de Tumor/inmunología , Ratones , Neoplasias Ováricas/enzimología , Neoplasias Ováricas/inmunología , Neoplasias Peritoneales/inmunología , Microambiente Tumoral/inmunologíaRESUMEN
OBJECTIVE: The objective of this study was to investigate the preoperative diagnostic value of F-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography and computed tomography (PET/CT) in patients with ovarian cancer. METHODS: One hundred sixty patients suspected of having malignant ovarian tumors were included in this study. All patients underwent FDG-PET/CT scans before operation, and the maximum standardized uptake value (SUVmax) of the primary tumor was measured. We evaluated the diagnostic accuracy of SUVmax for detecting malignancy and its relationship with histological findings. RESULTS: Postoperative pathological diagnoses showed that 67 were malignant, 14 were borderline malignant, and 79 were benign tumors. With the use of a cutoff SUVmax of 2.9 obtained from the receiver operating characteristic curve analysis, the sensitivity, specificity, positive predictive value, and negative predictive value for detecting malignancy were 80.6%, 94.6%, 91.5%, and 87.1%, respectively. Positive FDG accumulation (SUVmax ≥ 2.9) was shown in 89.5% of serous adenocarcinoma and in 92.3% of endometrioid adenocarcinoma. In contrast, lower frequencies of positive FDG accumulation were shown in clear cell adenocarcinoma (54.5%), mucinous adenocarcinoma (66.7%), and metastatic carcinoma (66.7%), and the median SUVmax of these 3 histological types were significantly lower than those of serous and endometrioid types. In addition, a positive FDG accumulation was shown in all patients with malignant transformation of mature cystic teratoma. Finally, of the 14 borderline malignant tumors, only 2 (14.3%) showed positive FDG accumulation. CONCLUSIONS: The SUVmax on FDG-PET/CT is useful for differentiating ovarian cancer from borderline or benign tumor with a high specificity and positive predictive value. However, our data also demonstrated a lower FDG uptake value in clear cell or mucinous histological finding, suggesting that SUVmax may vary depending on the tumor histological subtype.
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Adenocarcinoma/diagnóstico por imagen , Fluorodesoxiglucosa F18 , Neoplasias Ováricas/diagnóstico por imagen , Radiofármacos , Adenocarcinoma/patología , Femenino , Humanos , Neoplasias Ováricas/patología , Ovario/patología , Tomografía de Emisión de PositronesRESUMEN
A rare case of mixed carcinoma of the cervix is reported, composed of a large-cell neuroendocrine carcinoma and an invasive intestinal-type mucinous adenocarcinoma. The large-cell neuroendocrine carcinoma was composed of solid nests, sheets, and trabeculae of medium-sized to large-sized cells, and was positive for chromogranin-A and CD56. The invasive intestinal-type mucinous adenocarcinoma showed sparsely scattered immunoreactivity for chromogranin-A. Using an X-chromosome clonality assay, these 2 components showed patterns of monoclonality. These results suggest that the large-cell neuroendocrine carcinoma may have arisen from the invasive mucinous adenocarcinoma.