RESUMO
BACKGROUND: Vulvar cancer and vaginal cancer are relatively rare tumors, and there had been no established treatment principles or guidelines to treat these rare tumors in Japan. The first version of the Japan Society of Gynecologic Oncology (JSGO) guidelines for the treatment of vulvar cancer and vaginal cancer was published in 2015 in Japanese. OBJECTIVE: The JSGO committee decided to publish the English version of the JSGO guidelines worldwide, and hope it will be a useful guide to physicians in a similar situation as in Japan. METHODS: The guideline was created according to the basic principles in creating the guidelines of JSGO. RESULTS: The guidelines consist of five chapters and five algorithms. Prior to the first chapter, basic items are described including staging classification and history, classification of histology, and definition of the methods of surgery, radiation, and chemotherapy to give the reader a better understanding of the contents of the guidelines for these rare tumors. The first chapter gives an overview of the guidelines, including the basic policy of the guidelines. The second chapter discusses vulvar cancer, the third chapter discusses vaginal cancer, and the fourth chapter discusses vulvar Paget's disease and malignant melanoma. Each chapter includes clinical questions, recommendations, backgrounds, objectives, explanations, and references. The fifth chapter provides supplemental data for the drugs that are mentioned in the explanation of clinical questions. CONCLUSION: Overall, the objective of these guidelines is to clearly delineate the standard of care for vulvar and vaginal cancer with the goal of ensuring a high standard of care for all women diagnosed with these rare diseases.
Assuntos
Neoplasias Vaginais/patologia , Neoplasias Vaginais/terapia , Neoplasias Vulvares/patologia , Neoplasias Vulvares/terapia , Feminino , Humanos , Japão , Pessoa de Meia-Idade , Doença de Paget Extramamária/patologia , Doença de Paget Extramamária/terapiaRESUMO
AIM: This study was conducted to evaluate the efficacy and the difference in effects of the oral neurokinin-1(NK-1) receptor antagonist aprepitant for chemotherapy-induced nausea/vomiting (CINV) in Japanese patients with gynecological cancer receiving highly emetogenic (cisplatin) and moderately emetogenic (carboplatin) chemotherapy. METHODS: Aprepitant was added during the second course of chemotherapy in Japanese patients with grade ≥ 2 (Common Terminology Criteria for Adverse Events, version 3.0) nausea and vomiting during the first course despite receiving antiemetic therapy (a first-generation 5-hydroxytryptamine 3 receptor antagonist + dexamethasone), and in patients who requested stronger antiemetic therapy despite only having grade 1 nausea and vomiting. The incidence of nausea and vomiting was compared between the first and second courses in each group. RESULTS: Ninety-six (55.5%) out of 173 patients received add-on therapy with aprepitant. There was a significant increase in the complete response (CR: no vomiting or salvage therapy) rate in the patients receiving aprepitant, with marked improvement being confirmed for delayed CINV. Stratified analysis showed that patients with delayed CINV treated with carboplatin had a significantly higher CR rate, while patients with both acute and delayed CINV treated with cisplatin had significantly higher CR rates. There was a positive correlation between the incidence of nausea and the incidence of vomiting in the patients treated with aprepitant. CONCLUSION: The oral NK-1 receptor antagonist aprepitant could be effective for both acute and delayed CINV with cisplatin and for delayed CINV with carboplatin in Japanese gynecological cancer patients.
Assuntos
Antineoplásicos/efeitos adversos , Carboplatina/efeitos adversos , Cisplatino/efeitos adversos , Neoplasias dos Genitais Femininos/tratamento farmacológico , Morfolinas/farmacologia , Náusea/tratamento farmacológico , Antagonistas dos Receptores de Neurocinina-1/farmacologia , Avaliação de Resultados em Cuidados de Saúde , Vômito/tratamento farmacológico , Adulto , Idoso , Aprepitanto , Feminino , Humanos , Japão , Pessoa de Meia-Idade , Morfolinas/administração & dosagem , Náusea/induzido quimicamente , Antagonistas dos Receptores de Neurocinina-1/administração & dosagem , Vômito/induzido quimicamenteRESUMO
Cell surface glycans change during the process of malignant transformation. To characterize and distinguish endometrial cancer and endometrium, we performed glycan profiling using an emerging modern technology, lectin microarray analysis. The three cell lines, two from endometrial cancers [well-differentiated type (G1) and poorly differentiated type (G3)] and one from normal endometrium, were successfully categorized into three independent groups by 45 lectins. Furthermore, in cancer cells, a clear difference between G1 and G3 type was observed for the glycans recognized with six lectins, Ulex europaeus agglutinin I (UEA-I), Sambucus sieboldiana agglutinin (SSA), Sambucus nigra agglutinin (SNA), Trichosanthes japonica agglutinin I (TJA-I), Amaranthus caudatus agglutinin (ACA), and Bauhinia purpurea lectin (BPL). The lectin microarray analysis using G3 type tissues demonstrated that stage I and stage III or IV were distinguished depending on signal pattern of three lectins, Dolichos biflorus agglutinin (DBA), BPL, and ACA. In addition, the analysis of the glycans on the ovarian cancer cells showed that only anticancer drug-sensitive cell lines had almost no activities to specific three lectins. Glycan profiling by the lectin microarray may be used to assess the characteristics of tumors and potentially to predict the success of chemotherapy treatment.
Assuntos
Neoplasias do Endométrio/metabolismo , Lectinas/metabolismo , Polissacarídeos/metabolismo , Análise Serial de Proteínas , Linhagem Celular Tumoral , Membrana Celular/metabolismo , Análise por Conglomerados , Neoplasias do Endométrio/patologia , Endométrio/metabolismo , Feminino , Humanos , Gradação de Tumores , Estadiamento de Neoplasias , Neoplasias Ovarianas/metabolismoRESUMO
OBJECTIVES: Before setting into the clinical trial using a combination of mammalian target of rapamycin (mTOR) inhibitors (rapamycin and everolimus) and other anticancer drugs, this study was conducted to confirm the efficacy of the new therapeutic strategy for ovarian clear cell adenocarcinoma (CCA), which targeted mTOR-hypoxia-induced factor (HIF) signal transduction system. MATERIALS AND METHODS: Using the cultured cells of CCA and animal models, alteration of mTOR-HIF cofactors and cell proliferation under the mTOR inhibitor-treated condition were analyzed. RESULTS: Mammalian target of rapamycin-HIF cofactors were inhibited dependent on concentration by mTOR inhibitor, resulting in suppression of the cultured CCA proliferation. However, von Hippel-Lindau was up-regulated at the messenger RNA level. In the nude mice with subcutaneously implanted CCA cells, apoptosis and necrosis were detected especially around the center of the tumors in the mTOR inhibitor-treated group more conspicuously than in the nontreated group. In the assessment of combination therapy with other antitumor agents, a combined treatment with mTOR inhibitor and chemotherapeutic agents caused a significant decrease in tumor size compared to the chemotherapeutic agents-only group. CONCLUSIONS: Treatment by mTOR inhibitor is expected to down-regulate the cell proliferation of the CCA as a new therapeutic strategy.
Assuntos
Adenocarcinoma de Células Claras/patologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Neoplasias Ovarianas/patologia , Transdução de Sinais/efeitos dos fármacos , Sirolimo/análogos & derivados , Sirolimo/farmacologia , Serina-Treonina Quinases TOR/antagonistas & inibidores , Adenocarcinoma de Células Claras/tratamento farmacológico , Adenocarcinoma de Células Claras/metabolismo , Adenocarcinoma de Células Claras/mortalidade , Animais , Antibióticos Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Western Blotting , Proliferação de Células/efeitos dos fármacos , Quimioterapia Combinada , Everolimo , Feminino , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Técnicas Imunoenzimáticas , Imunossupressores/farmacologia , Técnicas In Vitro , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Proteína Oncogênica v-akt/genética , Proteína Oncogênica v-akt/metabolismo , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/mortalidade , Prognóstico , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Taxa de Sobrevida , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo , Células Tumorais Cultivadas , Proteína Supressora de Tumor Von Hippel-Lindau/genética , Proteína Supressora de Tumor Von Hippel-Lindau/metabolismo , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
OBJECTIVES: It is well known that a poorly differentiated endometrial adenocarcinoma shows more rapid progression and a worse response to therapy than a well-differentiated endometrial adenocarcinoma. Qualitative and quantitative changes of cell surface glycolipids occur during neoplastic transformation. Sulfatide is one of the sulfated glycolipids in the cell membrane that may have an important role in various functions such as cell adhesion. To examine the molecular background of the morphological and biological features of well-differentiated and poorly differentiated cancer, we measured the levels of lipids, especially glycolipids, in tumor tissues from patients with endometrial carcinoma. MATERIALS AND METHODS: We determined the composition of lipids and glycolipids in tumor tissues, investigated glycosyltransferase messenger RNA expression by the reverse transcription-polymerase chain reaction, and assessed the localization of galactosylceramide sulfotransferase (an enzyme involved in sulfatide biosynthesis) by immunohistochemical staining. RESULTS: No significant differences were observed between well-differentiated and poorly differentiated cancer with respect to the levels of cholesterol ester, cholesterol, phospholipids, cholesterol sulfate, ceramides, neutral glycolipids of the globo series, and GM3 ganglioside. However, the amount of sulfatides in well-differentiated tumors was significantly greater than that in poorly differentiated tumors, which was confirmed by thin-layer chromatography and immunostaining with a monoclonal antisulfatide antibody. Altered expression of sulfatide was found to be secondary to a change of galactosylceramide sulfotransferase messenger RNA expression. Immunohistochemical staining revealed that galactosylceramide sulfotransferase expression was characteristically observed in glandular areas but not in solid areas. CONCLUSION: These findings suggest that sulfatide contributes to the well-differentiated phenotype of endometrial adenocarcinoma and that it is being expressed in normal uterine endometrium at sites of gland formation during the luteal phase, as we have previously reported.
Assuntos
Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Diferenciação Celular , Neoplasias do Endométrio/metabolismo , Neoplasias do Endométrio/patologia , Sulfoglicoesfingolipídeos/metabolismo , Cromatografia em Camada Fina , Feminino , Humanos , Técnicas Imunoenzimáticas , Gradação de Tumores , Prognóstico , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sulfotransferases/genética , Sulfotransferases/metabolismoRESUMO
Many malignant epithelial tumors show increased expression of glucose transporter-1 (GLUT-1) and hexokinase II (HK-II), both of which are involved in glucose metabolism. GLUT-1 levels are often correlated with prognosis in these tumors. The current retrospective study was conducted to evaluate the importance of GLUT-1 and HK-II expression in leiomyosarcoma (LMS), a malignant uterine non-epithelial tumor with a poor prognosis. The subjects were 23 patients with stage I LMS. Expression of GLUT-1 and HK-II was evaluated immunohistochemically in samples removed surgically, and the MIB-1 index was evaluated as a measure of cell proliferation. The association of these results with prognosis was examined. Twenty samples of leiomyoma (LOM), a benign non-epithelial tumor, were used as controls. Immunohistochemical expression was defined as negative staining (-), weak to sporadic staining (1+), and strong staining (2+) per microscopic field, respectively. Malignancy was evaluated in 2000 cells and the MIB-1 index was calculated. Overall survival for LMS was estimated using the Kaplan-Meier method. Of the LMS cases, 12 were GLUT-1-positive (52.2%; 2+: 2, 1+: 10) and 15 were HK-II-positive (65.2%; 2+: 1, 1+: 14). GLUT-1 expression in LMS was significantly correlated with the MIB1 index. The 10-year survival rates were 90.9% and 58.3% in GLUT-1-negative and GLUT-1-positive cases, respectively, and 75.0% and 73.3% in HK-II-positive and HK-II-negative cases, respectively. GLUT-1 expression was significantly correlated with prognosis. Cases of stage I LMS showed a significant correlation between the expression level of GLUT-1 and the MIB-1 index, an indicator of malignancy. GLUT-1-negative cases had a better prognosis than GLUT-1-positive cases, suggesting that GLUT-1 expression is an effective prognostic marker.
RESUMO
This study was designed to clarify the mechanism of the mammalian target of rapamycin (mTOR)-hypoxia inducible factor-1 (HIF-1) pathway using the cultured cell strain derived from human ovarian clear cell adenocarcinoma (CCA). Everolimus (a derivative of rapamycin)-treated cells and non-treated cells did not show any difference in mTOR expression. But, phosphorylated-mTOR (p-mTOR) expression significantly decreased in the treated cells, and mTOR-related factors such as phosphorylated-4E-BP1 (p-4E-BP1), HIF-1α, and vascular endothelial growth factor (VEGF) in the downstream region of mTOR revealed a marked decrease in expression. The analysis of influences of the drug on the HIF-1α degradation system showed an increase in von-Hippel Lindau (VHL) expression in the treated cells. Increase of cleaved caspase-3, one of key factors involved in apoptosis, was also shown in the treated cells. In the next step, using nude mice implanted with RMG-1 cells, a decrease in tumor size was demonstrated in 4 of the 7 mice which were orally administered with everolimus. As a result, it was suggested that everolimus administration would be helpful as an anti-tumor therapy for CCA not only via down-regulation of p-mTOR but also degradation of HIF-1α by VHL and induction of apoptosis by cleaved caspase-3.
RESUMO
BACKGROUND: Appropriate surgical treatment of epithelial ovarian tumors is reliant on intraoperative diagnosis. A retrospective study to compare the diagnostic accuracies of imprint cytology (IC) with frozen section histology (FSH) in these tumors was performed. METHODS: About 78 cases of IC-based and FSH-based diagnoses against the final histopathologic diagnoses in terms of both histologic subtype (serous, mucinous, endometrioid, or clear cell tumor) and behavioral type (benign, borderline, or malignant) were compared. The cytomorphologic features of the tumor cells (nuclear atypia, papillary clusters, adenoma cells, and necrosis) in relation to behavioral types were also evaluated. RESULTS: While the diagnostic accuracy of IC and FSH were similar with respect to behavioral type (87% and 88%, respectively), the diagnostic accuracy of IC was superior to that of FSH with respect to histologic subtype (83% and 74%, respectively). Among histopathologically confirmed malignant tumors, the diagnostic accuracy of IC (62/64; 97%) was superior to that of FSH (58/64; 91%). The presence of necrosis and absence of adenoma cells were significantly more prevalent among malignant group than among borderline and benign groups (P < .01, for both). CONCLUSION: Since the presence of necrosis and absence of adenoma cells around the carcinoma cells appear useful in distinguishing malignant and borderline tumors, it was proposed to include IC for further intraoperative assessment of any tumors initially diagnosed as a borderline tumor by FSH.
Assuntos
Algoritmos , Carcinoma Epitelial do Ovário/diagnóstico , Citodiagnóstico/métodos , Secções Congeladas/métodos , Adulto , Idoso , Feminino , Humanos , Período Intraoperatório , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
The DNA-binding activity of hypoxia-inducible factor-1 alpha (HIF-1alpha) has been analyzed for various gynecological tumors. Among the tumors that were studied, there was a finding of a high level of DNA-binding HIF-1alpha activity, although it was limited to one case of adult type granulosa cell tumor (GCT). In this case a 60-year-old female had marked immunohistochemical expression of HIF-1alpha. The expressions of the mammalian target of rapamycin (mTOR) and phosphorylated-mTOR (p-mTOR) were also marked, and vascular endothelial growth factor (VEGF) was moderately expressed. To compare the expression profiles, 11 consecutive cases with adult type GCT were used. All cases showed marked expressions of HIF-1alpha and mTOR, but p-mTOR expression was moderately to markedly observed in four of the 12 cases. VEGF was expressed in all cases in varying degrees. Based on the evidence that downregulation of the mTOR pathway due to treatment with rapamycin (everolimus) would suppress tumor cell growth, an experimental study using the GCT cell line was designed to clarify whether HIF-1alpha and VEGF expressions decline. As a result, the expressions of p-mTOR, HIF-1alpha and VEGF were suppressed, but those of mTOR were not. It was concluded that mTOR-targeted therapy may represent a promising strategy for some GCT with an activated mTOR-HIF-1alpha-VEGF pathway.
Assuntos
Tumor de Células da Granulosa/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Neoplasias Ovarianas/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Adulto , Idoso , Western Blotting , Linhagem Celular Tumoral , Feminino , Tumor de Células da Granulosa/cirurgia , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Neoplasias Ovarianas/cirurgia , Transdução de Sinais/fisiologia , Serina-Treonina Quinases TORRESUMO
Diagnosis of malignant uterine tumor with continuous lesions from the uterine body to the cervix, i.e., endometrial or cervical cancer, depends on the main site of the lesions. However, it may be difficult to differentiate advanced cancer that is widespread in the uterus. We experienced a patient who was diagnosed with small cell neuroendocrine carcinoma (SCNEC) based on histopathological characteristics of SCNEC in the endometrium. This tumor frequently coexists with endometrioid carcinoma, but we had difficulty finding the original site of SCNEC in the endometrium. The patient was a 59-year-old, two-parous woman who underwent hysterectomy after diagnosis of malignant uterine tumor. Preoperative cervical and endometrial histology permitted diagnosis of SCNEC. Imaging showed that most of the anterior uterine wall from the uterine body to cervix was replaced by tumors. Histopathologic findings for the resected uterus showed that most of these tumors were SCNEC, but components of endometrioid carcinoma had developed from the endometrium just beneath the fundus to the lower uterine body. The growth pattern of endometrioid carcinoma was endophytic. Based on this finding, the patient was diagnosed with endometrial SCNEC associated with endometrioid carcinoma. The patient initially responded well after postoperative chemotherapy, but early recurrence led to death at three months after the first treatment. This case shows that SCNEC in the uterine body is likely to coexist with endometrioid carcinoma. These findings are useful to determine the original site in postoperative pathological diagnosis of highly advanced tumors. SCNEC is a rapidly progressive and aggressive tumor in clinical practice, but some cases have a relatively good initial response to chemotherapy and it is important to start treatment early.
Assuntos
Carcinoma Endometrioide/diagnóstico , Carcinoma Endometrioide/cirurgia , Carcinoma Neuroendócrino/diagnóstico , Carcinoma Neuroendócrino/cirurgia , Carcinoma de Células Pequenas/diagnóstico , Carcinoma de Células Pequenas/cirurgia , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/cirurgia , Neoplasias Primárias Múltiplas , Antineoplásicos/administração & dosagem , Biomarcadores Tumorais/sangue , Carcinoma Endometrioide/tratamento farmacológico , Carcinoma Endometrioide/patologia , Carcinoma Neuroendócrino/tratamento farmacológico , Carcinoma Neuroendócrino/patologia , Carcinoma de Células Pequenas/tratamento farmacológico , Carcinoma de Células Pequenas/patologia , Terapia Combinada , Diagnóstico Diferencial , Imagem de Difusão por Ressonância Magnética , Progressão da Doença , Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/patologia , Evolução Fatal , Feminino , Humanos , Histerectomia , Pessoa de Meia-Idade , Cuidados Pós-OperatóriosRESUMO
The patient was a 69-year-old multiparous female (gravida/para, 3/3) who had hypertension and arrhythmia. Her history included cerebral infarction treated with conservative therapy. She visited our hospital for atypical genital bleeding. She was diagnosed with atypical glandular cells (AGC) based on cervical cytology, atypical cells in endometrial cytology, and atypical endometrial hyperplasia on preoperative endometrial biopsy, and underwent total laparoscopic hysterectomy. However, in a postoperative pathologic examination, she was diagnosed with stage IB1 cervical adenocarcinoma without endometrial abnormality. AGC appeared in cervical cytology before surgery, but a surgical plan was not made with consideration of cervical adenocarcinoma.
Assuntos
Adenocarcinoma/cirurgia , Histerectomia/métodos , Laparoscopia/métodos , Neoplasias do Colo do Útero/cirurgia , Adenocarcinoma/patologia , Idoso , Endométrio/patologia , Feminino , Humanos , Hiperplasia , Neoplasias do Colo do Útero/patologiaRESUMO
INTRODUCTION: Somatostatin and its analogues inhibit the growth of various kinds of endocrine and exocrine cells via the somatostatin receptor (SSTR). Expression of SSTR2A has been reported in many well-differentiated neuroendocrine tumors and small numbers of poorly differentiated neuroendocrine carcinomas. SSTR2A-positive neuroendocrine tumors may be treatable by SS analogues. Uterine cervical neuroendocrine carcinoma is generally associated with poor prognosis. MATERIALS AND METHODS: We examined the expression of SSTR2A and other neuroendocrine markers [neural cell adhesion molecule (NCAM), chromogranin A, and synaptophysin] by immunohistochemical methods in seven neuroendocrine tumors of the uterine cervix: five small cell carcinomas and two large cell neuroendocrine carcinomas. RESULTS: SSTR2A was expressed in one small cell carcinoma and two neuroendocrine large cell carcinomas. The cell membrane of cells in these carcinomas showed strong immunohistochemical reactivity for SSTR2A. SSTR2A-positive cases are also frequently positive for the expression of chromogranin A. Treatment with SSTR2A may be effective for endocrine tumors. The results indicate the usefulness of SSTR2A analogs for the treatment of some uterine neuroendocrine carcinomas.
Assuntos
Carcinoma Neuroendócrino/metabolismo , Receptores de Somatostatina/biossíntese , Neoplasias do Colo do Útero/metabolismo , Adulto , Idoso , Biomarcadores/metabolismo , Cromogranina A , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Moléculas de Adesão de Célula Nervosa/metabolismo , Sinaptofisina/metabolismo , Adulto JovemRESUMO
We report an unusual case of endometrial adenocarcinoma in a 80-year-old woman who underwent mastectomy for breast cancer at 68 years of age. The tumor diffusely involved the entire thickness of the myometrium. Atypical cells throughout the tumor contained abundant oxiphilic cytoplasm and were arranged in a solid or solid-tubular nests in a focal papillary manner. Components of the carcinoma were focally observed in situ. The tumor was classified according to the International Federation of Gynecology and Obstetrics (FIGO) as grade 2 and stage IIIa. Immunohistochemistry revealed that the tumor cells were positive for p53 but negative for vimentin, estrogen, and progesterone receptors, GCDFP-15, and mammaglobin. They were positive for antimitochondrial antigen and thyroid transcription factor-1. The Ki-67 labeling index was approximately 50%. Immunostaining revealed endometrial oncocytic carcinoma. Distinguishing between primary uterine neoplasm and carcinoma caused by metastasis of breast cancer appears important.
Assuntos
Adenocarcinoma/patologia , Neoplasias do Endométrio/patologia , Segunda Neoplasia Primária/patologia , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/cirurgia , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carboplatina/administração & dosagem , Quimioterapia Adjuvante , Terapia Combinada , Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/cirurgia , Feminino , Humanos , Histerectomia , Imuno-Histoquímica , Segunda Neoplasia Primária/diagnóstico , Paclitaxel/administração & dosagemRESUMO
Bevacizumab is an effective drug for recurrent/advanced cervical cancer. A 59-year-old patient diagnosed with FIGO stage I B2 squamous cell carcinoma of the cervix at our hospital was treated with concurrent chemoradiotherapy as initial treatment. The outcome was judged as close to CR. Local recurrence in the irradiation field and paraaortic lymph node metastasis were noted 2 months after completion of this treatment. Chemotherapy of bevacizumab combined with paclitaxel plus carboplatin (TC) was initiated for recurrent cervical cancer. At 17 days after the 4th cycle, abdominal pain suddenly developed, and a close examination detected free air on abdominal CT, based on which intestinal perforation was diagnosed. Laparoscopic surgery performed to investigate the intraabdominal cavity showed that the small intestine was perforated at 2 sites. These were treated with laparoscopy-assisted partial resection of the small intestine and functional end-to-end anastomosis. Drug therapy for the recurrent cervical cancer was considered, but the primary disease rapidly aggravated and the patient died of the primary disease 11 months after completion of the initial treatment.
Assuntos
Anastomose Cirúrgica/métodos , Anti-Inflamatórios não Esteroides/efeitos adversos , Bevacizumab/efeitos adversos , Carcinoma de Células Escamosas/terapia , Perfuração Intestinal/induzido quimicamente , Perfuração Intestinal/cirurgia , Intestino Delgado/cirurgia , Laparoscopia/métodos , Recidiva Local de Neoplasia/terapia , Neoplasias do Colo do Útero/terapia , Anti-Inflamatórios não Esteroides/administração & dosagem , Bevacizumab/uso terapêutico , Quimiorradioterapia , Evolução Fatal , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
The patient was a 50-year-old multiparous female (gravida/para 4/2) who had divorced. She was followed up for 1 year and 5 months after completion of initial treatment for peritoneal cancer (preoperative chemotherapy + optimal surgery + chemotherapy). A gradual increase in the tumor marker CA125 occurred, and computed tomography and ultrasonography showed bilateral neck, left supraclavicular and right axillary lymphadenopathy. The patient wanted to continue her job. Therefore, she was treated with etoposide (25 mg) daily for 3 weeks and TJ-48 (juzen-taihoto, 7.5 g) daily for 4 weeks, and then followed up. After two weeks, swelling of lymph nodes had been reduced or eliminated and tumor marker CA125 was negative. The only adverse reaction was slight numbness and the patient continued to work while receiving the same drugs orally for 2 years and 8 months without any symptoms or recurrence. This case shows that a combination of etoposide and TJ-48 has an antitumor effect on recurrent progressive peritoneal cancer while allowing a patient to work and have a normal daily life.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Medicamentos de Ervas Chinesas/uso terapêutico , Etoposídeo/uso terapêutico , Neoplasias Peritoneais/tratamento farmacológico , Atividades Cotidianas , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Antígeno Ca-125/sangue , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/efeitos adversos , Etoposídeo/administração & dosagem , Etoposídeo/efeitos adversos , Feminino , Humanos , Proteínas de Membrana/sangue , Pessoa de Meia-Idade , Neoplasias Peritoneais/diagnóstico por imagem , Neoplasias Peritoneais/patologia , Resultado do TratamentoRESUMO
The expression of hypoxia inducible factor-1alpha (HIF-1alpha) and glucose transporter-1 (GLUT-1) was immunohistochemically analyzed in ovarian adenocarcinomas with the aim of elucidating whether hypoxic status is associated with histological type or structural character. The following ovarian adenocarcinomas were used: serous adenocarcinoma (SEA), 21 cases; mucinous adenocarcinoma (MUA), 19 cases; endometrioid adenocarcinoma (ENA), 16 cases; clear cell adenocarcinoma (CLA), 19 cases. High-level expression (3+) of HIF-1alpha was observed in 100% of SEAs, 58% of MUAs, 100% of ENAs and 89% of CLAs, and high-level expression of GLUT-1 in 76% of SEAs, 26% of MUAs, 50% of ENAs and 67% of CLAs. Heterogeneous or localized staining was relatively evident for GLUT-1. Immunohistochemical profiles were in accord with the immunoblotting and mRNA levels of both markers. ELISA for the detection of active HIF-1 demonstrated that HIF-1 is strongly activated in SEAs, ENAs and CLAs as compared to MUAs. Our results show that GLUT-1 overexpression is to some extent regulated by HIF-1alpha and is also strongly associated with histological features, i.e., papillary or stratified structure accompanied by little or no vascular stroma. In conclusion, hypoxic status differs according to the histological type of ovarian adenocarcinoma and the micro-environmental conditions of each type.
Assuntos
Adenocarcinoma/patologia , Fatores de Transcrição Hélice-Alça-Hélice Básicos/biossíntese , Hipóxia Celular/fisiologia , Transportador 2 de Aminoácido Excitatório/biossíntese , Neoplasias Ovarianas/patologia , Adenocarcinoma/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Western Blotting , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Neoplasias Ovarianas/metabolismo , RNA Mensageiro/análise , Reação em Cadeia da Polimerase Via Transcriptase ReversaAssuntos
Ascite Quilosa/prevenção & controle , Ascite Quilosa/terapia , Neoplasias dos Genitais Femininos/cirurgia , Doenças Linfáticas/prevenção & controle , Doenças Linfáticas/terapia , Complicações Pós-Operatórias/prevenção & controle , Adulto , Feminino , Humanos , Excisão de Linfonodo , Complicações Pós-Operatórias/terapiaRESUMO
Thymidine phosphorylase (TP) is structurally similar to platelet-derived endothelial cell growth factor, and it activates 5-fluorouracil (5-FU) prodrugs and also promotes angiogenesis. In the present study, the possibility of using TP expression as a biomarker for 5-FU prodrugs, and the significance of TP as an angiogenic factor, were investigated in patients with gynecological tumors. The subjects enrolled in the study were 188 patients with gynecological tumors who provided informed consent and underwent tumor resection at the Department of Obstetrics and Gynecology of Tokai University Hospital between February 2002 and January 2010. Measurement of the enzymatic activity of TP and dihydropyrimidine dehydrogenase (DPD) was performed by enzyme-linked immunosorbent assay. In addition, immunohistochemistry (IHC) analysis of microvessels by monochrome imaging, western blotting and reverse transcription-polymerase chain reaction were performed. The mean TP activity and the TP/DPD ratio were increased in squamous cell carcinoma of the cervix (306.9 and 2.2 U/mg protein, respectively) and adenosquamous carcinoma (317.6 and 1.4 U/mg protein, respectively) compared with benign tumors and other malignancies, including endometrial (uterine) carcinoma, ovarian serous adenocarcinoma and ovarian mucinous adenocarcinoma. However, these parameters were also elevated in other histological types of cancer such as clear cell adenocarcinoma of the ovary (115.2 and 2.1 U/mg protein, respectively), in which the microvessel area was the largest of all the histological types analyzed. Since high TP expression and a high TP/DPD ratio were identified in other tumors besides cervical cancer, it is possible that patients for whom 5-FU prodrugs are indicated could be selected appropriately if their TP activity is determined and their TP expression is analyzed by IHC prior to initiation of the treatment.
RESUMO
We compared the preoperative serum tumor marker values and diameters of ovarian tumors between 14 stage Ia ovarian cancer patients with a good prognosis and 14 stage Ic patients with a poor prognosis. The aim was to examine the usability of tumor markers and diameter of ovarian tumors for prognostic diagnosis of clinically advanced phases. In occult neoplastic cells (ONCs), a tumor marker indicative of recurrence and metastasis, the cytokeratin-positive cells in lymph node biopsies, were also compared. In a preoperative comparison of serum tumor markers, CA125 levels in stage Ia and Ic patients were 47.1+/-15.9 (median, 31.9 U/ml) and 370.6+/-146.2 U/ml (median, 135.6 U/ml), respectively (p=0.0457), and CA19-9 levels were 25.5+/-5.5 (median, 20.4 U/ml) and 564.5+/-192.4 U/ml (median, 248.0 U/ml), respectively (p=0.0131). In a comparison of tumor diameters during surgery, diameters of stage Ia and Ic patients were 117.3+/-11.4 (median, 100.0 mm) and 182.0+/-29.2 mm (median, 145.0 mm), respectively (p=0.0457). ONCs were not detected in any stage Ia patients, but detected in 3 (30%) stage Ic patients. In conclusion, clinical progression was evaluated using CA125 and CA19-9 serum markers and tumor diameters in stage Ia and Ic patients, and demonstrated significant differences between stage. ONCs were only detected in the lymph nodes of stage Ic patients.