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Carcinosarcomas are high-grade endometrial cancers which enclose mesenchymal and epithelial differentiated components. The vast majority of these cancers belong to the p53 abnormal molecular subgroup and usually come with an unfavorable prognosis. POLE mutant carcinosarcomas are a rarity and only make up about 5% of this histologic subtype. Recent literature even suggests that this number is still an overestimation and the result of misclassification of undifferentiated or dedifferentiated endometrial cancers. Here we present a case of a 56-years old patient diagnosed with carcinosarcoma of the uterus. Hysterectomy, bilateral salpingo-oophorectomy with pelvic lymph node staging was performed and complete molecular workup of the tumor revealed an abnormal p53 expression as well as a pathologic POLE mutation. NGS was performed separately on the epithelial and mesenchymal component of this high-grade cancer and both components shared two identical POLE mutations, a known pathologic mutation, and a variant of unknown significance (VUS). This finding hints to a clonal origin of both histologic components of this tumor and supports conversion theory as mechanism of carcinosarcoma emergence. The cancer was correctly staged as FIGO 2023 Stage IAmPOLEmut and according to ESGO-ESTRO-ESP guidelines adjuvant chemotherapy no longer considered and our patient entered follow-up after a detailed discussion.
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OBJECTIVE: Gynecological sarcomas account for 3% of all gynecological malignancies and are associated with a poor prognosis. Due to the rarity and heterogeneity of gynecological sarcomas there is still no consensus on optimal therapeutic strategies. This study's objective was to describe the treatment strategies used in patients with gynecological sarcomas in the primary course of disease. METHODS: The German prospective registry for gynecological sarcoma (REGSA) is the largest registry for gynecological sarcomas in Germany, Austria and Switzerland. Primary inclusion criteria for REGSA are histological diagnosis of sarcoma of the female genital tract, sarcoma of the breast or uterine smooth muscle tumors of uncertain malignant potential (STUMP). We evaluated data of the REGSA registry on therapeutic strategies used for primary treatment from August 2015 to February 2021. RESULTS: A total of 723 patients from 120 centers were included. Data on therapeutic strategies for primary treatment were available in 605 cases. Overall, 580 (95.9%) patients underwent primary surgery, 472 (81.4%) of whom underwent only hysterectomy. Morcellation was reported in 11.4% (n=54) of all hysterectomies. A total of 42.8% (n=202) had no further surgical interventions, whereas an additional salpingo-ophorectomy was performed in 54% (n=255) of patients. An additional lymphadenectomy was performed in 12.7% (n=60), an omentectomy in 9.5% (n=45) and intestinal resection in 6.1% (n=29) of all patients. Among 448 patients with available information, 21.4% (n=96) received chemo- or targeted therapies, more commonly as single-agent treatment than as drug combinations. Information about anti-hormonal treatment was available for 423 patients, among which 42 (9.9%) received anti-hormonal treatment, 23 (54.8%) of whom with low-grade endometrial stroma sarcomas. For radiotherapy, data of 437 patients were available, among which 29 (6.6%) patients underwent radiotherapy. CONCLUSION: Our study showed that treatment of patients with gynecologic sarcomas is heterogeneous. Further trials are needed along with more information on treatment modalities, therapy response and patient-reported outcomes to implement new treatment strategies.
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Neoplasias do Endométrio , Ginecologia , Sarcoma , Neoplasias Uterinas , Humanos , Feminino , Sarcoma/epidemiologia , Sarcoma/terapia , Sarcoma/patologia , Histerectomia , Alemanha/epidemiologia , Neoplasias do Endométrio/patologia , Neoplasias Uterinas/patologia , Estudos RetrospectivosRESUMO
Backround: The primary aim of this study was to investigate information needs and treatment preferences of patients with ovarian cancer, focusing especially on physician-patient relationship and treatment. Patients and methods: A questionnaire was developed based on the experiences of the national German survey 'Expression II', and was provided to patients with ovarian cancer either at initial diagnosis or with recurrent disease via Internet (online-version) or as print-out-version. Results: From December 2009 to October 2012, a total of 1830 patients with ovarian cancer from eight European countries (Austria, Belgium, France, Germany, Italy, Poland, Romania, Spain) participated, 902 (49.3%) after initial diagnosis and 731 (39.9%) with recurrent ovarian cancer. The median age was 58 years (range 17-89). Nearly all patients (96.2%) had experienced upfront surgery followed by first-line chemotherapy (91.8%). The majority of patients were satisfied with the completeness and comprehensibility of the explanation about the diagnosis and treatment options. The three most important aspects, identified by patients to improve the treatment for ovarian cancer included: 'the therapy should not induce alopecia' (42%), 'there must be more done to counter fatigue' (34.5%) and 'the therapy should be more effective' (29.7%). Out of 659 (36%) patients, who were offered participation in a clinical trial, 476 (26%) were included. Conclusion: This study underlines the high need of patients with ovarian cancer for all details concerning treatment options irrespective of their cultural background, the stage of disease and the patient's age. Increased information requirements regarding potential side effects and treatment alternatives were recorded. Besides the need for more effective therapy, alopecia and fatigue are the most important side effects of concern to patients.
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Neoplasias Ovarianas/psicologia , Neoplasias Ovarianas/terapia , Pacientes/psicologia , Relações Médico-Paciente , Adulto , Idoso , Europa (Continente) , Feminino , Necessidades e Demandas de Serviços de Saúde , Humanos , Pessoa de Meia-Idade , Inquéritos e QuestionáriosRESUMO
Paclitaxel and carboplatin combination chemotherapy has remained the standard of care in the front-line therapy of advanced epithelial ovarian cancer during the last decade. Maintenance chemotherapy has not been proven to impact on overall survival. Acceptable alternatives include weekly paclitaxel plus 3-weekly carboplatin, the addition of bevacizumab to 3-weekly carboplatin and paclitaxel, and intraperitoneal chemotherapy. In particular, anti-angiogenic therapy has been identified as the most promising targeted therapy, and the addition of bevacizumab to first-line chemotherapy followed by a maintenance period of bevacizumab in monotherapy has shown to prolong progression-free survival. This was considered the proof of concept of the value of anti-angiogenic therapy in the front-line of ovarian cancer, and the results of two additional clinical trials with anti-angiogenic tyrosine kinase inhibitors have shown results in the same direction.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Epiteliais e Glandulares/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Bevacizumab/administração & dosagem , Carboplatina/administração & dosagem , Carcinoma Epitelial do Ovário , Feminino , Humanos , Paclitaxel/administração & dosagem , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
BACKGROUND: Neopterin is produced by activated macrophages upon stimulation with interferon-γ (IFN-γ) and thus, elevated neopterin concentrations in patients indicate cellular inate immune response. Most studies in patients with malignant diseases found an association between higher neopterin concentrations and reduced survival and impaired prognosis. Nevertheless, neopterin is not a classical tumor marker since it is not produced by the cancer cells themselves. PATIENTS AND METHODS: In a study conducted by the Austrian Gynecologic Oncology Group (AGO) in 114 patients with ovarian cystadenomas and 223 patients with invasive ovarian cancer, patients' urinary neopterin was determined before and after primary therapy. The relevance of neopterin in long-term median follow-up was assessed. RESULTS: Elevated levels (cut-off 250 µmol/mol creatinine) were found less frequently in women with benign ovarian cystadenomas (24%) than in patients with malignant disease (58%). After 10 years, only 57% of ovarian cancer patients with elevated urinary neopterin levels survived without disease progression following primary therapy when compared with 86% of women with normal levels (P < 0.001). Along with residual tumor, FIGO stage, age and histological type, neopterin was significantly associated with overall survival (OS) and progression-free survival (PFS). The median PFS was 52 and 12 months and the median OS was 81 and 24 months for patients with normal and elevated neopterin, respectively, P < 0.001. In a multivariate Cox regression analysis, only residual tumor, neopterin and age were independently associated with OS, while only residual tumor was predictive for PFS. Thirty patients with early-stage invasive ovarian cancer (FIGO I and II) were analyzed separately. Of 3 patients with elevated neopterin, 2 died of disease in contrast to 2 out of 27 patients with normal neopterin (P = 0.004). CONCLUSION: In ovarian cancer, the negative impact of elevated urinary neopterin levels indicates a detrimental effect of cancer-associated inflammatory reaction.
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Biomarcadores Tumorais/urina , Imunidade Inata/efeitos dos fármacos , Neopterina/urina , Neoplasias Ovarianas/urina , Adulto , Idoso , Áustria , Intervalo Livre de Doença , Feminino , Humanos , Interferon gama/administração & dosagem , Interferon gama/urina , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasia Residual/patologia , Neoplasia Residual/urina , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologiaRESUMO
OBJECTIVE: Cytoreductive surgery and platinum-based systemic therapy constitute the standard treatment of patients with advanced ovarian cancer. The aim of the present study was to evaluate whether the time interval from surgery to start of chemotherapy has an impact on clinical outcome. METHODS: Data of 191 patients with advanced serous (FIGO III-IV) ovarian cancer from the prospective multicenter study OVCAD (OVarian CAncer Diagnosis) were analyzed. All patients underwent primary surgery followed by platinum-based chemotherapy. RESULTS: The 25%, 50%, and 75% quartiles of intervals from surgery to start of chemotherapy were 22, 28, and 38 days, respectively (range, 4-158 days). Preoperative performance status (P<0.001), extent of surgery (P<0.001), and perioperative complications (P<0.001) correlated with intervals from surgery to initiation of chemotherapy. Timing of cytotoxic treatment [≤ 28 days versus >28 days; hazard ratio (HR) 1.73 (95% confidence interval 1.08-2.78), P=0.022], residual disease [HR 2.95 (95% confidence interval 1.87-4.67), P<0.001], and FIGO stage [HR 2.26 (95% confidence interval 1.41-3.64), P=0.001] were significant prognostic factors for overall survival in multivariate analysis. While the interval from surgery to start of chemotherapy did not possess prognostic significance in patients without postoperative residual disease (n=121), it significantly correlated with overall survival in patients with postoperative residual disease [n=70, HR 2.24 (95% confidence interval 1.08-4.66), P=0.031]. CONCLUSION: Our findings suggest that delayed initiation of chemotherapy might compromise overall survival in patients with advanced serous ovarian cancer, especially when suboptimally debulked.
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Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma/tratamento farmacológico , Carcinoma/patologia , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Tempo para o Tratamento , Carcinoma/cirurgia , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasia Residual , Neoplasias Ovarianas/cirurgia , Modelos de Riscos Proporcionais , Taxa de Sobrevida , Fatores de TempoRESUMO
Because of its semi-solid character in dissemination and growth, advanced ovarian cancer with its hundreds of peritoneal tumor nodules and plaques appears to be an excellent in vivo model for studying the cancer stem cell hypothesis. The most important obstacle, however, is to adequately define and isolate these tumor-initiating cells endowed with the properties of anoikis-resistance and unlimited self-renewal. Until now, no universal single marker or marker constellation has been found to faithfully isolate (ovarian) cancer stem cells. As these multipotent cells are known to possess highly elaborated efflux systems for cytotoxic agents, these pump systems have been exploited to outline putative stem cells as a side-population (SP) via dye exclusion analysis. Furthermore, the cells in question have been isolated via flow cytometry on the basis of cell surface markers thought to be characteristic for stem cells.In the Vienna variant of the ovarian cancer cell line A2780 a proof-of-principle model with both a stable SP and a stable ALDH1A1+ cell population was established. Double staining clearly revealed that both cell fractions were not identical. Of note, A2780V cells were negative for expression of surface markers CD44 and CD117 (c-kit). When cultured on monolayers of healthy human mesothelial cells, green-fluorescence-protein (GFP)-transfected SP of A2780V exhibited spheroid-formation, whereas non-side-population (NSP) developed a spare monolayer growing over the healthy mesothelium. Furthermore, A2780V SP was found to be partially resistant to platinum. However, this resistance could not be explained by over-expression of the "excision repair cross-complementation group 1" (ERCC1) gene, which is essentially involved in the repair of platinated DNA damage. ERCC1 was, nonetheless, over-expressed in A2780V cells grown as spheres under stem cell-selective conditions as compared to adherent monolayers cultured under differentiating conditions. The same was true for the primary ovarian cancer cells B-57.In summary our investigations indicate that even in multi-passaged cancer cell lines hierarchic government of growth and differentiation is conserved and that the key cancer stem cell population may be composed of small overlapping cell fractions defined by various arbitrary markers.
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Células-Tronco Neoplásicas/fisiologia , Neoplasias Ovarianas/patologia , Animais , Separação Celular , Técnicas de Cocultura , Proteínas de Ligação a DNA/genética , Resistencia a Medicamentos Antineoplásicos , Ensaios de Seleção de Medicamentos Antitumorais , Endonucleases/genética , Feminino , Humanos , Neoplasias Ovarianas/tratamento farmacológicoRESUMO
BACKGROUND: Overexpression of L1-cell adhesion molecule (L1CAM) has been observed for various carcinomas and correlates with poor prognosis and late-stage disease. In vitro, L1CAM enhances proliferation, cell migration, adhesion and chemoresistance. We tested L1CAM and interleukin-1 beta (IL-1ß) expression in tumor samples and ascitic fluid from ovarian carcinoma patients to examine its role as a prognostic marker. PATIENTS AND METHODS: We investigated tumor samples and ascitic fluid from 232 serous ovarian carcinoma patients for L1CAM by enzyme-linked immunosorbent assay. L1CAM expression was correlated with pathoclinical parameters and patients' outcome. IL-1ß levels were measured in tumor cell lysates. Ovarian cancer cell lines were analyzed for the contribution of L1CAM to IL-1ß production and nuclear factor 'kappa-light-chain-enhancer' of activated B-cells (NF-κB) activation. RESULTS: We observed that L1CAM-expressing tumors show a highly invasive phenotype associated with restricted tumor resectability at primary debulking surgery and increased lymphogenic spread. Soluble L1CAM proved to be a marker for poor progression-free survival and chemoresistance. In ovarian carcinoma cell lines, the specific knock-down of L1CAM reduces IL-1ß expression and NF-κB activity. CONCLUSIONS: L1CAM expression contributes to the invasive and metastatic phenotype of serous ovarian carcinoma. L1CAM expression and shedding in the tumor microenvironment could contribute to enhanced invasion and tumor progression through increased IL-1ß production and NF-κB activation.
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Carcinoma/metabolismo , NF-kappa B/metabolismo , Molécula L1 de Adesão de Célula Nervosa/metabolismo , Neoplasias Ovarianas/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Líquido Ascítico/metabolismo , Carcinoma/mortalidade , Carcinoma/secundário , Carcinoma/terapia , Linhagem Celular Tumoral , Intervalo Livre de Doença , Feminino , Humanos , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Estimativa de Kaplan-Meier , Metástase Linfática , Pessoa de Meia-Idade , Análise Multivariada , Invasividade Neoplásica , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/terapia , Fenótipo , Prognóstico , Adulto JovemRESUMO
The prognosis of breast cancer is most heavily influenced by the status of the axillary nodes. Until a few years ago, this knowledge was gained through radical axillary lymph node clearance. In the meantime, sentinel lymph node clearance has become an established part of the surgical treatment of breast cancer. With the development of this procedure, the morbidity caused by axillary dissection has been reduced significantly. Although comprehensive prospective, randomised data regarding the safe use of the sentinel concept are only now available, the focus currently, however, is on the question of whether in the case of positive sentinel lymph nodes, an axillary dissection can be done away with altogether without having any negative impact on the risk of loco-regional recurrence or on progression-free survival and overall survival. The results of the American ACOSOG-Z001 study have changed the fundamental perspective of this. In this study on the advantages of axillary dissection following the confirmation of tumour tissue in the sentinel lymph nodes, there were no statistically significant advantages from axillary dissection for women with a favourable overall risk profile who had received radiotherapy and systemic therapy. If this concept takes hold, the surgical treatment of node-positive breast cancer, at least in the axilla, would be reduced to a minimum, and the focus of treatment would in future lie more on the systemic treatment of this condition. As part of an interdisciplinary consensus meeting, a standardised approach for Austria with regard to this question was decided upon.
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BACKGROUND: We aimed to evaluate the clinical relevance of p53 and p73 isoforms that modulate the function of p53. METHODS: This prospective multicentre study included 154 patients with stage III and IV serous ovarian cancer. A functional yeast-based assay and subsequent sequencing were performed to analyse the p53 mutational status. Expression of p53 and p73 isoforms was determined using RT-qPCR. RESULTS: Δ133p53 expression constituted an independent prognostic marker for recurrence-free (hazard ratio=0.571, P=0.016, 95% CI: 0.362-0.899) and overall survival (hazard ratio=0.365, P=0.004, 95% CI: 0.182-0.731) in patients with p53 mutant ovarian cancer (n=121). High Δ40p53 expression was associated with favourable tumour grading (P=0.037) and improved recurrence-free survival (33.4 vs 19.6 months, P=0.029), but not overall survival (43.1 vs 33.6 months, P=0.139), in patients with p53 wild-type cancer (n=33). Neither the p53 mutational status nor p73 isoform expression possessed prognostic significance in the examined ovarian cancer cases. CONCLUSION: Δ133p53 expression was associated with prognosis in the vast majority of ovarian cancer cases, that is, patients with p53 mutant advanced serous carcinomas. Thus, our findings underline the importance of considering the complex p53 regulatory network.
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Biomarcadores Tumorais/metabolismo , Neoplasias Ovarianas/patologia , Prognóstico , Proteína Supressora de Tumor p53/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Genes p53 , Humanos , Pessoa de Meia-Idade , Mutação , Neoplasias Ovarianas/metabolismo , Estudos Prospectivos , Reação em Cadeia da Polimerase em Tempo Real , Proteína Supressora de Tumor p53/genéticaRESUMO
Recently we showed an integral epidermal growth factor receptor (EGFR)-E2F3a signaling path, in which E2F3a was found to be essential in EGFR-mediated proliferation in ovarian cancer cells. The present work evaluates the clinical relevance of this novel axis and of E2F3a itself in a large set of 130 ovarian cancer specimens. For this purpose E2F3a and its counterpart, E2F3b, were measured by RT-PCR and activated EGFR was assessed by immunohistochemistry. When compared with healthy control tissue, both E2F3 isoforms were overexpressed in the cancers, but only E2F3a expression correlated with tumor stage (ρ=0.349, P=0.0001) and residual disease (ρ=0.254, P=0.004). Univariate survival analyses showed E2F3a and activated EGFR to be associated with poor PFS and OS. Furthermore, a strong, positive correlation between activated EGFR and E2F3a expression was shown (P=0.0001). We further identified two EGFR-independent mechanisms that regulate E2F3a expression, namely one, acting by promoter methylation of miR-34a, which by its physical interaction with E2F3a transcripts causes their degradation, and the second based on 6p22 gene locus amplification. MiRIDIAN-based knockdown and induction of miR-34a evidenced a direct regulatory link between miR-34a and E2F3a, and the tumor-suppressive character of miR-34a was documented by its association with improved survival. Although, 6p22 gene locus amplification was detected in a significant number of ovarian cancer specimens, 6p22 ploidy was not relevant in predicting survival. In Cox regression analysis, E2F3a, but not activated EGFR or miR-34a expression, retained independent prognostic significance (PFS: hazards ratio 3.785 (1.326-9.840), P=0.013; OS: hazards ratio 4.651 (1.189-15.572), P=0.013). These clinical findings highlight the relevance of E2F3a in the biology of ovarian cancer. Moreover, identification of EGFR-independent mechanisms in E2F3a control can be helpful in explaining the non-responsiveness of therapeutic EGFR targeting in ovarian cancer.
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Fator de Transcrição E2F3/fisiologia , Neoplasias Ovarianas/patologia , Idoso , Cromossomos Humanos Par 6 , Metilação de DNA , Fator de Transcrição E2F3/análise , Fator de Transcrição E2F3/genética , Receptores ErbB/fisiologia , Feminino , Amplificação de Genes , Humanos , MicroRNAs/genética , Pessoa de Meia-Idade , Neoplasias Ovarianas/química , Neoplasias Ovarianas/genética , Prognóstico , Regiões Promotoras GenéticasRESUMO
PURPOSE: We assessed the value of contrast-enhanced US for differentiating between benign and malignant axillary lymph nodes in breast cancer. MATERIALS AND METHODS: A total of 120 axillary lymph nodes in 92 patients with breast cancer were studied. All patients underwent grayscale US examination, unenhanced and enhanced color and power Doppler US, and enhanced grayscale harmonic US examination. RESULTS: The mean size of the 120 axillary lymph nodes was 1.5 cm (range 0.5 - 3.4 cm). Of all 120 axillary lymph nodes studied, 80 (67 %) were malignant and 40 (33 %) were benign according to pathological examination. The total number of vessels in baseline US did not increase between benign and malignant lymph nodes (3.3 +/- 2.2 vs. 5.4 +/- 4.0; p > 0.05). The total number of peripheral vessels was 0.5 +/- 0.8 for benign lymph nodes vs. 2.0 +/- 1.7 for malignant lymph nodes (p > 0.05). Enhanced US studies showed enhancement in both benign and malignant lymph nodes after contrast administration with a significantly higher degree of enhancement in malignant lymph nodes (p < 0.01). The total number of vessels was significantly higher in malignant lymph nodes after contrast administration (17.3 +/- 8.0 vs. 8.2 +/- 5.1, p < 0.01). Malignant lymph nodes demonstrated longer contrast enhancement duration compared to benign lymph nodes. CONCLUSION: This preliminary data shows that contrast-enhanced US can differentiate between benign and malignant lymph nodes in breast cancer.
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Neoplasias da Mama/diagnóstico por imagem , Aumento da Imagem/métodos , Linfonodos/diagnóstico por imagem , Metástase Linfática/diagnóstico por imagem , Ultrassonografia Doppler em Cores/métodos , Ultrassonografia Mamária/métodos , Idoso , Axila/diagnóstico por imagem , Neoplasias da Mama/irrigação sanguínea , Neoplasias da Mama/patologia , Meios de Contraste/administração & dosagem , Feminino , Humanos , Linfonodos/irrigação sanguínea , Linfonodos/patologia , Metástase Linfática/patologia , Pessoa de Meia-Idade , Neovascularização Patológica/diagnóstico por imagemRESUMO
Similar to p73, the tumor suppressor gene p53 is subject to alternative splicing. Besides p53DeltaE6 and p53beta, we identified p53zeta, p53delta and p53varepsilon, arising from alternative splicing of exon 6 and intron 9, respectively. p53 splice variants were present in 18 of 34 ovarian cancer cell lines (52.9%) and 134 of 245 primary ovarian cancers (54.7%). p53delta expression was associated with impaired response to primary platinum-based chemotherapy (P=0.032). Also, p53delta expression constituted an independent prognostic marker for recurrence-free and overall survival (hazard ratio 1.854, 95% confidence interval 1.121-3.065, P=0.016; and hazard ratio 1.937, 95% confidence interval 1.177-3.186, P=0.009, respectively). p53beta expression was associated with adverse clinicopathologic markers, that is, serous and poorly differentiated cancers (P=0.002 and P=0.008, respectively), and correlated with worse recurrence-free survival in patients exhibiting functionally active p53 (P=0.049). DeltaN'p73 constituted the main N-terminally truncated p73 isoform and was preferentially found in ovarian cancer cell lines showing functionally active p53, supporting our hypothesis that N-terminally truncated p73 isoforms can alleviate the selection pressure for p53 mutations by the inhibition of p53 protein function.
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Processamento Alternativo , Proteínas de Ligação a DNA/genética , Proteínas Nucleares/genética , Neoplasias Ovarianas/genética , Proteína Supressora de Tumor p53/genética , Proteínas Supressoras de Tumor/genética , Feminino , Humanos , Íntrons , Proteína Tumoral p73 , Proteína Supressora de Tumor p53/metabolismoRESUMO
BACKGROUND: A case of cervical cancer associated with irreducible procidentia successfully treated with external beam radiation and extracorporeal HDR-AL with concomitant chemotherapy followed by obliterative vaginal surgery is reported for the first time. CASE: A 73-year-old woman presented in frail condition suffering from a huge, irreducible uterovaginal procidentia combined with a squamous cell carcinoma of the cervix in FIGO Stage IIa. Successful treatment consisted of sequential application of combined radiotherapy with concurrent cisplatin chemotherapy followed by total vaginal hysterectomy and partial colpectomy with colpocleisis according to the Labhardt method. The five-year follow-up documents the excellent long-term results with regard to cervical cancer and pelvic floor stability. CONCLUSION: Especially in patients ineligible for extended surgery, radiochemotherapy followed by an obliterative surgical approach is feasible without aberrant wound healing and constitutes a suitable and efficient option for treating carcinomas of the cervix associated with irreducible genital prolapse.
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Antineoplásicos/uso terapêutico , Carcinoma de Células Escamosas/terapia , Cisplatino/uso terapêutico , Neoplasias do Colo do Útero/terapia , Prolapso Uterino/terapia , Idoso , Antineoplásicos/administração & dosagem , Carcinoma de Células Escamosas/patologia , Quimioterapia Adjuvante , Cisplatino/administração & dosagem , Feminino , Idoso Fragilizado , Humanos , Histerectomia Vaginal , Terapia Neoadjuvante , Radioterapia Adjuvante , Neoplasias do Colo do Útero/patologia , Prolapso Uterino/patologiaRESUMO
OBJECTIVE: To report an uncommon case of a recurrent episode of primarily paraneoplastic dermatomyositis which was completely disconnected from the initially triggering malignancy and manifested as a silent pure multivisceral exacerbation. CASE: A 70-year-old woman presented with a pure multivisceral episode of dermatomyositis without characteristic musculo-cutaneous symptoms one year after successful treatment of fallopian tube carcinoma with complete resolvement of a concomittant paraneoplastic dermatomyositis. The uncommon manifestation of recurrent dermatomyositis involving the lungs, spleen and liver, both adrenal glands and abdominal lymph nodes, mimicked a highly disseminated recurrence of the fallopian tube cancer. Physicians participating in the interdisciplinary tumor board were misled to opt for reinductive chemotherapy. Only histologic diagnosis obtained from multiple biopsies uncovered the inflammatory nature of the disease and spared the patient unneeded chemotherapy. CONCLUSION: Asymptomatic multivisceral dermatomyositis may mimic metastatic spread of the initially underlying malignancy and may misdirect therapeutic strategies towards inadequate antineoplastic treatment.
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Carcinoma/complicações , Dermatomiosite/fisiopatologia , Neoplasias das Tubas Uterinas/complicações , Síndromes Paraneoplásicas/fisiopatologia , Corticosteroides/uso terapêutico , Idoso , Pneumonia em Organização Criptogênica/diagnóstico por imagem , Pneumonia em Organização Criptogênica/etiologia , Dermatomiosite/complicações , Dermatomiosite/tratamento farmacológico , Feminino , Humanos , Síndromes Paraneoplásicas/tratamento farmacológico , Recidiva , Tomografia Computadorizada por Raios XAssuntos
Dermatomiosite/diagnóstico , Neoplasias das Tubas Uterinas/diagnóstico , Síndromes Paraneoplásicas/diagnóstico , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Combinada , Diagnóstico Diferencial , Neoplasias das Tubas Uterinas/tratamento farmacológico , Neoplasias das Tubas Uterinas/patologia , Neoplasias das Tubas Uterinas/cirurgia , Feminino , Humanos , Tomografia por Emissão de Pósitrons , Recidiva , Tomografia Computadorizada por Raios XRESUMO
OBJECTIVE: The aim of this study was to investigate the feasibility of sentinel node detection with the blue dye technique in early cervical cancer. METHODS: In a retrospective study conducted between January 2000 and February 2005, 47 women with early cervical cancer (6 patients FIGO Stage I A, 38 patients FIGO Stage I B, 2 patients FIGO Stage II A, 1 patient FIGO Stage II B) who underwent class II-III radical hysterectomy with pelvic lymphadenectomy were identified. Prior to surgery 1 ml of blue dye (lymphazurin 1%) was injected into the four quadrants of the cervix. RESULTS: The detection rate for sentinel nodes was 83% (39/47 patients). The median number of sentinel lymph nodes per patient was two. Nine patients had positive sentinel nodes. In one patient the sentinel lymph node procedure revealed to be false-negative. Positive predictive value and specificity were both 100%. The sensitivity and negative predictive value were 90% and 97%, respectively. CONCLUSIONS: Sentinel node detection has become a main field of interest in gynecological oncology. Our detection rate and sensitivity rate using the blue dye technique in cervical cancer are comparable to those in previously published data. However, recent data on a combined radioactively labeled albumin and blue dye technique show even more promising results. The clinical validity of the combined techniques must be evaluated prospectively in larger studies.
Assuntos
Linfonodos/patologia , Corantes de Rosanilina , Biópsia de Linfonodo Sentinela , Neoplasias do Colo do Útero/patologia , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Adulto , Idoso , Carcinoma Adenoescamoso/patologia , Carcinoma Adenoescamoso/cirurgia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Estudos de Viabilidade , Feminino , Humanos , Histerectomia , Técnicas Imunoenzimáticas , Excisão de Linfonodo , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Sensibilidade e Especificidade , Neoplasias do Colo do Útero/cirurgiaRESUMO
OBJECTIVES: Platinum resistance is a significant problem in patients with ovarian cancer. The aim of this phase II study was to define the response rates, the progression-free survival and the toxicity profile of the combination of PEG liposomal doxorubicin (L-DXR) and gemcitabine (GEM). MATERIAL AND METHODS: Thirty one patients with histologically confirmed platinum-refractory or -resistant epithelial ovarian cancer were scheduled to receive 6 cycles of L-DXR 30 mg/m(2) on day 1 as well as GEM 650 mg/m(2) on days 1 and 8 every 28 days. RESULTS: The median number of chemotherapy cycles given was 4. The mean dose intensity for L-DXR and GEM on day 1 was 96% and 97%, respectively. The mean dose intensity for GEM on day 8 was 93%. The overall response rate was 33% (10 of 30 evaluable patients; 20% complete responses). The median progression-free survival was 3.8 months, and the median overall survival was 15.8 months, respectively. Toxicity was acceptable. One quarter of patients developed grade 3 or 4 neutropenia, but none developed febrile neutropenia. Palmoplantar erythrodysesthesia (PPE) grades 2 and 3 occurred in 13% and 3% only, respectively, and no grade 4 PPE was observed. Grades 1 to 3 stomatitis was found in 58% of patients (10% grade 3). CONCLUSION: The combination of L-DXR and GEM is an active and acceptably tolerated option in the treatment of patients with platinum-resistant and -refractory ovarian cancer. Dose reductions seem advisable in the case of > or =grade 2 stomatitis and/or PPE > or =grade 2.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Desoxicitidina/análogos & derivados , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Doxorrubicina/análogos & derivados , Feminino , Humanos , Pessoa de Meia-Idade , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/efeitos adversos , Qualidade de Vida , GencitabinaRESUMO
Gene therapeutic approaches currently favor adenoviral vectors over alternatively available vector systems. Ovarian cancer represents an attractive model for an intraperitoneal adenovirus-based gene therapy, which is now under intensive clinical investigation. Adenovirus-mediated gene transfer depends on adequate virus uptake and thus on the presence of sufficient amounts of high-affinity coxsackie-adenovirus receptor (CAR) and alphavbeta3- and alphavbeta5 integrins on target cells. This fact has been ignored in most ongoing clinical trials. This investigation, therefore, determined expression of CAR by immunohistochemistry in 37 ovarian carcinomas and compared it with that of alphavbeta3 and alphavbeta5 integrins. In all samples, except one undifferentiated carcinoma, CAR was immunohistochemically demonstrable. Grade 1 tumors exhibited stronger CAR immunostaining as compared with higher-grade cancers (P < 0.03). Integrins alphavbeta3 and alphavbeta5 were detectable in 62% and 65% of carcinomas, respectively, and staining for both classes correlated positively (P < 0.005). Cancers classified as undifferentiated completely lacked alphavbeta3 expression. Furthermore, in undifferentiated and grade 3 carcinomas the three molecules studied exhibited marked distributional heterogeneity with regard to focal positivity and negativity within the same tumor. Either the absence of CAR, alphavbeta3 and alphavbeta5 or the pronounced heterogeneity in their expression might seriously compromise the efficiency of adenovirus-based gene therapy in ovarian cancer.
Assuntos
Técnicas de Transferência de Genes , Vetores Genéticos/metabolismo , Integrinas/metabolismo , Neoplasias Ovarianas/metabolismo , Receptores Virais/metabolismo , Adenoviridae/genética , Proteína de Membrana Semelhante a Receptor de Coxsackie e Adenovirus , Feminino , Terapia Genética , Humanos , Proteínas de Neoplasias/metabolismo , Estadiamento de Neoplasias , Neoplasias Ovarianas/patologia , Receptores de Vitronectina/metabolismoRESUMO
A growing body of evidence supports the hypothesis that the retinoic acid receptor beta2 (RAR-beta2) gene is a tumor suppressor gene which induces apoptosis and that the chemopreventive and therapeutic effects of retinoids are due to induction of RAR-beta2. During breast cancer progression, RAR-beta2 is reduced or even lost. It is known from studies of other tumor-suppressor genes that methylation of the 5'-region is the cause of loss of expression. Several groups demonstrated that this is also true for the RAR-beta2 in breast cancer by treating breast cancer cell lines with a demethylating agent and examining expression of the RAR-beta2 gene in response to a challenge with retinoic acid. Studies using sodium bisulfite genomic sequencing as well as methylation specific PCR showed that a number of breast cancer cell lines as well as breast cancer tissue showed signs of methylation. The RAR-beta2 gene was unmethylated in non-neoplastic breast tissue as well as in other normal tissues. A combination of retinoic acid with demethylating agents as well as with histone deacetylase inhibitors acts synergistically to inhibit growth. This review presents data that suggest that treatment of cancer patients with demethylating agents followed by retinoic acid may offer a new therapeutic modality. Both the time of commencement of chemoprevention and the choice of substances that are able either to prevent de novo methylation or to reverse methylation-caused gene silencing may be important considerations.