RESUMO
Oral and oropharyngeal cancer represents the sixth more common type of cancer affecting the worldwide population. It has been estimated the number of 650,000 new cases per year globally and a greater prevalence has been registered among men. The main risk factors for oral cancer such as tobacco smoking and alcohol are uncontroversial and have been deeply investigated and evidenced in the scientific literature. Recently, viral infections related to Human Papilloma Virus (HPV), with the genotype 16 and 32, have shown a correlation mainly with oropharyngeal cancer (OPC) especially in the non-smoking and non-drinkers young adults. Its transmission is mainly related to sexually transmitted diseases (STDs) although its involvement in oral squamous cell carcinoma (OSCC) is still unclear. This review aims to explore the hypotheses of the OSCC etiology and other possible risk factors, such as chronic traumatisms, chronic periodontitis, and poor oral hygiene that affect directly the oral mucosa and might trigger the carcinogenesis process that should not be underestimated. Furthermore, in the last 10 years, the role of oral microbiome gained attention as a predicting biomarker, for a possible bacterial, viral, and fungal involvement in tumorigenesis.
Assuntos
Carcinoma de Células Escamosas , Microbiota , Neoplasias Bucais , Papillomaviridae , Infecções por Papillomavirus , Humanos , Neoplasias Bucais/epidemiologia , Neoplasias Bucais/etiologia , Papillomaviridae/genética , Infecções por Papillomavirus/complicações , Fatores de Risco , NicotianaRESUMO
This observational survey aimed to demonstrate the use of the Snus kind of smokeless tobacco, among young Italian adults from alpine areas. A customized anonymous questionnaire was purposely created using the Google Forms platform and made it available for 4 weeks through social media supports to a cohort of young adults living in a mountain area in Italy. Out of four hundred recipients, 332 interviewees returned the survey. Participants had a mean age of 22.8, range 17-40 years. One hundred fifty regular consumers used Snus for more than 5 years. Gingival changes were reported in 92 subjects, associated with gingival bleeding in 14 subjects. 79 subjects reported discoloration of the mucosa. The 50% of the habitual users developed an addiction to Snus and 90% didn't smoke conventional cigarettes. In Italian young adults the use of Snus tobacco could be an adjunctive risk factor for the oral mucosa. It is essential to extend and spread the awareness about this addictive habit among dental professionals, to give to the patients a reliable and effective oral and systemic education.
Assuntos
Mídias Sociais , Tabaco sem Fumaça , Adolescente , Adulto , Estudos de Coortes , Humanos , Itália/epidemiologia , Inquéritos e Questionários , Tabaco sem Fumaça/efeitos adversos , Adulto JovemRESUMO
BACKGROUND: There is no clear consensus regarding systemic treatment of early-stage ovarian cancer (OC). Clinical trials are challenging because of the relatively low incidence and good prognosis. Initial results of the International Collaborative Ovarian Neoplasm (ICON)1 trial demonstrated benefit in both overall survival (OS) and recurrence-free survival (RFS) with adjuvant chemotherapy. We report results of 10-year follow-up to establish whether benefits are maintained longer term and discuss how this and other available evidence from randomised trials can be used to guide treatment options regarding the need for, and choice of, adjuvant chemotherapy regimen. PATIENTS AND METHODS: ICON1 recruited women with OC following primary surgery in whom there was uncertainty as to whether adjuvant chemotherapy was indicated. Patients were randomly assigned to adjuvant or no adjuvant chemotherapy. Platinum-based chemotherapy was recommended and 87% received single-agent carboplatin. Analyses of long-term treatment benefits and interaction with risk groups were carried out. A high-risk group of women was defined with stage 1B/1C grade 2/3, any stage 1 grade 3 or clear-cell histology. RESULTS: With a median follow-up of 10 years, the estimated hazard ratio (HR) for RFS was 0.69 [95% confidence interval (CI) 0.51-0.94, P = 0.02] and OS 0.71 (95% CI 0.52-0.98, P = 0.04) in favour of chemotherapy. In absolute terms, there was a 10% (60%-70%) improvement in RFS and a 9% (64%-73%) improvement in OS; the benefit of chemotherapy might be greater in high-risk disease (18% improvement in OS). Uncertainty remains about the optimal chemotherapy regimen. The only randomised trial data available are from a subset of 120 stage 1 patients in ICON3 where the treatment difference, comparing carboplatin with carboplatin/paclitaxel was estimated with relatively wide CIs [progression-free survival HR = 0.71 (95% CI 0.39-1.32) and OS HR = 0.98 (95% CI 0.49-1.93)]. CONCLUSIONS: Extended follow-up from ICON1 confirms that adjuvant chemotherapy should be offered to women with early-stage OC, particularly those with high-risk disease. CLINICAL TRIAL NUMBERS: ISRCTN11916376 for ICON1 and ISRCTN57157825 for ICON3.
Assuntos
Neoplasias Epiteliais e Glandulares/tratamento farmacológico , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Compostos de Platina/uso terapêutico , Adulto , Idoso , Carcinoma Epitelial do Ovário , Quimioterapia Adjuvante , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Epiteliais e Glandulares/mortalidade , Neoplasias Ovarianas/mortalidadeRESUMO
OBJECTIVES: The aim of this study was to estimate the rate of malignancy in adnexal lesions described as unilocular cysts at transvaginal ultrasound examination and to investigate if there are differences in clinical and ultrasound characteristics between benign and malignant unilocular cysts. METHODS: A total of 3511 patients with an adnexal mass underwent transvaginal ultrasound examination between 1999 and 2007. Sonologists used the International Ovarian Tumor Analysis terms and definitions to describe their ultrasound findings. Only masses operated on within 120 days after the ultrasound examination were included in the analysis and the histopathological diagnosis of the mass was used as the gold standard. RESULTS: Of the 3511 masses, 1148 (33%) were classified as unilocular cysts on ultrasound. Of these, 11 (0.96% (95% CI, 0.48-1.71)) were malignant. The malignancy rate was lower in premenopausal than in postmenopausal women: 0.54% (5/931; 95% CI, 0.17-1.25) vs. 2.76% (6/217; 95% CI, 1.02-5.92); P = 0.009. More patients with malignant unilocular cysts had a personal history of breast cancer (18% vs. 2%; P = 0.02) or ovarian cancer (18% vs 0.6%; P = 0.003). Hemorrhagic cyst contents on ultrasound were more common in malignant than in benign unilocular cysts (18% vs. 2%; P = 0.03). In seven of the 11 malignancies judged to be unilocular cysts at scan, papillary projections or other solid components were seen at macroscopic inspection of the surgical specimen. CONCLUSIONS: The malignancy rate in surgically removed adnexal lesions judged to be unilocular cysts at transvaginal scan is c 1%. Postmenopausal status, personal history of breast or ovarian cancer and hemorrhagic cyst contents on ultrasound increase the risk of malignancy. To avoid misclassifying adnexal lesions as unilocular cysts at scan, it is important to scrutinize unilocular cysts for the presence of solid components.
Assuntos
Cistos Ovarianos/diagnóstico por imagem , Neoplasias Ovarianas/diagnóstico por imagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Diagnóstico Diferencial , Feminino , Humanos , Pessoa de Meia-Idade , Cistos Ovarianos/patologia , Neoplasias Ovarianas/patologia , Pós-Menopausa , Pré-Menopausa , Estudos Retrospectivos , Fatores de Risco , Ultrassonografia Doppler em Cores/métodos , Adulto JovemRESUMO
OBJECTIVES: To develop a logistic regression model for discrimination between benign and malignant unilocular solid cysts with papillary projections but no other solid components, and to compare its diagnostic performance with that of subjective evaluation of ultrasound findings (subjective assessment), CA 125 and the risk of malignancy index (RMI). METHODS: Among the 3511 adnexal masses in the International Ovarian Tumor Analysis (IOTA) database there were 252 (7%) unilocular solid cysts with papillary projections but no other solid components ('unilocular cysts with papillations'). All had been examined with transvaginal ultrasound using the IOTA standardized research protocol. The ultrasound examiner had also classified each mass as certainly or probably benign, unclassifiable, or certainly or probably malignant. A logistic regression model to discriminate between benignity and malignancy was developed for all unilocular cysts with papillations (175 tumors in the training set and 77 in the test set) and for unilocular cysts with papillations for which the ultrasound examiner was not certain about benignity/malignancy (113 tumors in the training set and 53 in the test set). The gold standard was the histological diagnosis of the surgically removed adnexal mass. RESULTS: A model containing six variables was developed for all unilocular cysts with papillations. The model had an area under the receiver-operating characteristics curve (AUC) on the test set of 0.83 (95% CI, 0.74-0.93). The optimal risk cut-off, as defined on the training set (0.35), resulted in sensitivity 69% (20/29), specificity 79% (38/48), positive likelihood ratio (LR +) 3.31 and negative likelihood ratio (LR-) 0.39 on the test set. The corresponding values for subjective assessment when using the ultrasound examiner's dichotomous classification of the mass as benign or malignant were 97% (28/29), 79% (38/48), 4.63 and 0.04. A model containing four variables was developed for unilocular cysts with papillations for which the ultrasound examiner was not certain about benignity/malignancy. The model had an AUC of 0.74 (95% CI, 0.60-0.88) on the test set. The optimal risk cut-off of the model, as defined on the training set (0.30), resulted in sensitivity 57% (12/21), specificity 78% (25/32), LR + 2.61 and LR- 0.55 on the test set. The corresponding values for subjective assessment were 95% (20/21), 78% (25/32), 4.35 and 0.06. CA 125 and RMI had virtually no diagnostic ability. CONCLUSIONS: Even though logistic regression models to predict malignancy in unilocular cysts with papillations can be developed, they have at most moderate performance and are not superior to subjective assessment for discrimination between benignity and malignancy.
Assuntos
Doenças dos Anexos/patologia , Cistos/patologia , Neoplasias Ovarianas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígeno Ca-125/metabolismo , Diagnóstico Diferencial , Feminino , Humanos , Pessoa de Meia-Idade , Cuidados Pré-Operatórios/métodos , Estudos Prospectivos , Estudos Retrospectivos , Adulto JovemRESUMO
OBJECTIVES: To describe clinical and ultrasound features of Brenner tumors of the ovary. METHODS: In this retrospective study, the databases of the International Ovarian Tumor Analysis (IOTA) studies and one tertiary center were searched to identify patients who had undergone an ultrasound scan before surgery for an adnexal mass that proved to be a Brenner tumor. Twenty-eight patients with 29 Brenner tumors were included, most of which had been collected within the framework of the IOTA studies. An experienced ultrasound examiner reviewed available ultrasound images (available for 14 tumors), searching for a pattern specific to Brenner tumors. RESULTS: Most patients were postmenopausal and asymptomatic. Twenty-four (83%) tumors were benign, two (7%) were borderline and three (10%) were malignant. Most benign tumors (17/24, 71%) contained solid components and manifested no or minimal blood flow on Doppler examination (19/24, 79%). Information about calcifications was available for 15 benign tumors, and in 13 (87%) calcifications were present. The five borderline and invasively malignant tumors contained solid components less often than did the benign ones (3/5, 60%) and were more richly vascularized on Doppler examination. Information about calcifications was available for four borderline or invasively malignant tumors, and in three (75%) calcifications were present. CONCLUSION: We failed to demonstrate ultrasound features specific to Brenner tumors. A prospective study is needed to determine if ultrasound features of calcifications can discriminate between Brenner tumors and other types of ovarian tumor.
Assuntos
Tumor de Brenner/diagnóstico por imagem , Neoplasias Ovarianas/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Tumor de Brenner/patologia , Tumor de Brenner/cirurgia , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/cirurgia , Cuidados Pré-Operatórios/métodos , Prognóstico , Estudos Retrospectivos , Carga Tumoral , Ultrassonografia Doppler em CoresRESUMO
OBJECTIVE: To determine the diagnostic performance of ultrasound-based simple rules, risk of malignancy index (RMI), two logistic regression models (LR1 and LR2) and real-time subjective assessment by experienced ultrasound examiners following the exclusion of masses likely to be judged as easy and 'instant' to diagnose by an ultrasound examiner, and to develop a new strategy for the assessment of adnexal pathology based on this. METHODS: 3511 patients with at least one persistent adnexal mass preoperatively underwent transvaginal ultrasonography to assess tumor morphology and vascularity. They were included in two consecutive prospective studies by the International Ovarian Tumor Analysis (IOTA) group: Phase 1 (1999-2005), development of the simple rules and logistic regression models LR1 and LR2, and Phase 2, a validation study (2005-2007). RESULTS: Almost half of the cases (43%) were identified as 'instant' to diagnose on the basis of descriptors applied to the database. To assess diagnostic performance in the more difficult 'non-instant' masses, we used only Phase 2 data (n = 1036). The sensitivity of LR2 was 88%, of RMI it was 41% and of subjective assessment it was 87%. The specificity of LR2 was 67%, of RMI it was 90% and of subjective assessment it was 86%. The simple rules yielded a conclusive result in almost 2/3 of the masses, where they resulted in sensitivity and specificity similar to those of real-time subjective assessment by experienced ultrasound examiners: sensitivity 89 vs 89% (P = 0.76), specificity 91 vs 91% (P = 0.65). When a three-step strategy was applied with easy 'instant' diagnoses as Step 1, simple rules where conclusive as Step 2 and subjective assessment by an experienced ultrasound examiner in the remaining masses as Step 3, we obtained a sensitivity of 92% and specificity of 92% compared with sensitivity 90% (P = 0.03) and specificity 93% (P = 0.44) when using real-time subjective assessment by experts in all tumors. CONCLUSION: A diagnostic strategy using simple descriptors and ultrasound rules when applied to the variables contained in the IOTA database obtains results that are at least as good as those obtained by subjective assessment of a mass by an expert.
Assuntos
Doenças dos Anexos/diagnóstico por imagem , Neoplasias dos Genitais Femininos/diagnóstico por imagem , Adulto , Diagnóstico Diferencial , Detecção Precoce de Câncer , Feminino , Humanos , Modelos Logísticos , Pessoa de Meia-Idade , Cuidados Pré-Operatórios/métodos , Medição de Risco , Fatores de Risco , Sensibilidade e Especificidade , UltrassonografiaRESUMO
OBJECTIVES: To estimate the ability to discriminate between benign and malignant adnexal masses of different size using: subjective assessment, two International Ovarian Tumor Analysis (IOTA) logistic regression models (LR1 and LR2), the IOTA simple rules and the risk of malignancy index (RMI). METHODS: We used a multicenter IOTA database of 2445 patients with at least one adnexal mass, i.e. the database previously used to prospectively validate the diagnostic performance of LR1 and LR2. The masses were categorized into three subgroups according to their largest diameter: small tumors (diameter < 4 cm; n = 396), medium-sized tumors (diameter, 4-9.9 cm; n = 1457) and large tumors (diameter ≥ 10 cm, n = 592). Subjective assessment, LR1 and LR2, IOTA simple rules and the RMI were applied to each of the three groups. Sensitivity, specificity, positive and negative likelihood ratio (LR+, LR-), diagnostic odds ratio (DOR) and area under the receiver-operating characteristics curve (AUC) were used to describe diagnostic performance. A moving window technique was applied to estimate the effect of tumor size as a continuous variable on the AUC. The reference standard was the histological diagnosis of the surgically removed adnexal mass. RESULTS: The frequency of invasive malignancy was 10% in small tumors, 19% in medium-sized tumors and 40% in large tumors; 11% of the large tumors were borderline tumors vs 3% and 4%, respectively, of the small and medium-sized tumors. The type of benign histology also differed among the three subgroups. For all methods, sensitivity with regard to malignancy was lowest in small tumors (56-84% vs 67-93% in medium-sized tumors and 74-95% in large tumors) while specificity was lowest in large tumors (60-87%vs 83-95% in medium-sized tumors and 83-96% in small tumors ). The DOR and the AUC value were highest in medium-sized tumors and the AUC was largest in tumors with a largest diameter of 7-11 cm. CONCLUSION: Tumor size affects the performance of subjective assessment, LR1 and LR2, the IOTA simple rules and the RMI in discriminating correctly between benign and malignant adnexal masses. The likely explanation, at least in part, is the difference in histology among tumors of different size.
Assuntos
Doenças dos Anexos/patologia , Neoplasias Ovarianas/patologia , Doenças dos Anexos/diagnóstico por imagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígeno Ca-125/sangue , Criança , Diagnóstico Diferencial , Feminino , Humanos , Modelos Logísticos , Pessoa de Meia-Idade , Neoplasias Ovarianas/diagnóstico por imagem , Risco , Sensibilidade e Especificidade , Ultrassonografia , Adulto JovemRESUMO
OBJECTIVE: To develop a logistic regression model that can discriminate between benign and malignant adnexal masses perceived to be difficult to classify by subjective evaluation of gray-scale and Doppler ultrasound findings (subjective assessment) and to compare its diagnostic performance with that of subjective assessment, serum CA 125 and the risk of malignancy index (RMI). METHODS: We used data from the 3511 patients with an adnexal mass included in the International Ovarian Tumor Analysis (IOTA) studies. All patients had been examined using transvaginal gray-scale and Doppler ultrasound following a standardized research protocol carried out by an experienced ultrasound examiner using a high-end ultrasound system. In addition to prospectively collecting information on > 40 clinical and ultrasound variables, the ultrasound examiner classified each mass as certainly or probably benign, unclassifiable, or certainly or probably malignant. A logistic regression model to discriminate between benignity and malignancy was developed for the unclassifiable masses (n = 244, i.e. 7% of all tumors) using a training set (160 tumors, 45 malignancies) and then tested on a test set (84 tumors, 28 malignancies). The gold standard was the histological diagnosis of the surgically removed adnexal mass. The area under the receiver-operating characteristics curve (AUC), sensitivity, specificity, positive likelihood ratio (LR+) and negative likelihood ratio (LR-) were used to describe diagnostic performance and were compared between subjective assessment, CA 125, the RMI and the logistic regression model created. RESULTS: One variable was retained in the logistic regression model: the largest diameter (in mm) of the largest solid component of the tumor (odds ratio (OR) = 1.04; 95% CI, 1.02-1.06). The model had an AUC of 0.68 (95% CI, 0.59-0.78) on the training set and an AUC of 0.65 (95% CI, 0.53-0.78) on the test set. On the test set, a cut-off of 25% probability of malignancy (corresponding to the largest diameter of the largest solid component of 23 mm) resulted in a sensitivity of 64% (18/28), a specificity of 55% (31/56), an LR+ of 1.44 and an LR- of 0.65. The corresponding values for subjective assessment were 68% (19/28), 59% (33/56), 1.65 and 0.55. On the test set of patients with available CA 125 results, the LR+ and LR- of the logistic regression model (cut-off = 25% probability of malignancy) were 1.29 and 0.73, of subjective assessment were 1.45 and 0.63, of CA 125 (cut-off = 35 U/mL) were 1.24 and 0.84 and of RMI (cut-off = 200) were 1.21 and 0.92. CONCLUSIONS: About 7% of adnexal masses that are considered appropriate for surgical removal cannot be classified as benign or malignant by experienced ultrasound examiners using subjective assessment. Logistic regression models to estimate the risk of malignancy, CA 125 measurements and the RMI are not helpful in these masses.
Assuntos
Doenças dos Anexos/diagnóstico por imagem , Neoplasias Ovarianas/diagnóstico por imagem , Ultrassonografia Doppler em Cores , Área Sob a Curva , Diagnóstico Diferencial , Feminino , Humanos , Modelos Logísticos , Pessoa de Meia-Idade , Probabilidade , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: A prospective phase II study was conducted to evaluate the efficacy and toxicity of oral gimatecan in patients with recurrent epithelial ovarian, fallopian tube or peritoneal cancer. PATIENTS AND METHODS: Patients had a maximum of three prior chemotherapy lines with no more than two prior platinum-containing regimens and a progression-free interval after the last dose of platinum <12 months. A total dose of 4 mg/m(2)/cycle (0.8 mg/m(2)/day from day 1 to day 5) was administered, repeated every 28 days. RESULTS: From June 2005 to December 2005, 69 assessable patients were enrolled. The best overall response to study treatment by combined CA-125 and RECIST criteria was partial response in 17 patients (24.6%) and disease stabilization in 22 patients (31.9%). The median time to progression and overall survival were 3.8 and 16.2 months, respectively. A total of 312 cycles were administered. Neutropenia grade 4 and thrombocytopenia grade 4 occurred in 17.4% and 7.2% of patients, respectively. Diarrhea grade 4 was never observed. Asthenia and fatigue were reported by 36.2% and 18.8% of patients, but were all grade 2 or less. CONCLUSION: Gimatecan is a new active agent in previously treated ovarian cancer with myelosuppression as main toxicity.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Camptotecina/análogos & derivados , Neoplasias das Tubas Uterinas/tratamento farmacológico , Neoplasias Epiteliais e Glandulares/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Peritoneais/tratamento farmacológico , Administração Oral , Adulto , Idoso , Antineoplásicos/administração & dosagem , Camptotecina/administração & dosagem , Quimioterapia Adjuvante , Neoplasias das Tubas Uterinas/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Ovarianas/patologia , Neoplasias Peritoneais/patologia , Platina/administração & dosagem , Recidiva , Taxoides/administração & dosagemRESUMO
OBJECTIVES: To describe the ultrasound characteristics of endometriomas in pre- and postmenopausal patients and to develop rules that characterize endometriomas. METHODS: All patients included in the International Ovarian Tumor Analysis (IOTA) studies were used in our analysis. Patients with an adnexal mass were scanned by experienced sonologists using a standardized research protocol. The gold standard was the histology of the surgically removed adnexal mass. The gray-scale and Doppler ultrasound characteristics of the endometriomas were compared with those of other benign and malignant masses. Based on decision-tree analysis, the existing literature and clinical experience, ultrasound rules for the detection of endometriomas were created and evaluated. RESULTS: Of all 3511 patients included in the IOTA studies, 713 (20%) had endometriomas. Fifty-one per cent of the endometriomas were unilocular cysts with ground glass echogenicity of the cyst fluid. These characteristics were found less often among other benign tumors or malignancies, or among the small set of endometriomas (4%) that were found in postmenopausal patients. Based on the decision-tree analysis, the optimal rule to detect endometriomas was 'an adnexal mass in a premenopausal patient with ground glass echogenicity of the cyst fluid, one to four locules and no papillations with detectable blood flow'. Based on clinical considerations, the following rule: 'premenopausal status, ground glass echogenicity of the cyst fluid, one to four locules and no solid parts' seems preferable. CONCLUSIONS: Several rules had a good ability to characterize endometriomas. The ultrasound characteristics of endometriomas differ between pre- and postmenopausal patients. Masses in postmenopausal women whose cystic contents have a ground glass appearance have a high risk of malignancy.
Assuntos
Endometriose/diagnóstico por imagem , Neoplasias Ovarianas/diagnóstico por imagem , Doenças dos Anexos/diagnóstico por imagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Endometriose/fisiopatologia , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/fisiopatologia , Ultrassonografia Doppler em Cores , Adulto JovemRESUMO
OBJECTIVES: The aims of the study were to temporally and externally validate the diagnostic performance of two logistic regression models containing clinical and ultrasound variables in order to estimate the risk of malignancy in adnexal masses, and to compare the results with the subjective interpretation of ultrasound findings carried out by an experienced ultrasound examiner ('subjective assessment'). METHODS: Patients with adnexal masses, who were put forward by the 19 centers participating in the study, underwent a standardized transvaginal ultrasound examination by a gynecologist or a radiologist specialized in ultrasonography. The examiner prospectively collected information on clinical and ultrasound variables, and classified each mass as benign or malignant on the basis of subjective evaluation of ultrasound findings. The gold standard was the histology of the mass with local clinicians deciding whether to operate on the basis of ultrasound results and the clinical picture. The models' ability to discriminate between malignant and benign masses was assessed, together with the accuracy of the risk estimates. RESULTS: Of the 1938 patients included in the study, 1396 had benign, 373 had primary invasive, 111 had borderline malignant and 58 had metastatic tumors. On external validation (997 patients from 12 centers), the area under the receiver-operating characteristics curve (AUC) for a model containing 12 predictors (LR1) was 0.956, for a reduced model with six predictors (LR2) was 0.949 and for subjective assessment was 0.949. Subjective assessment gave a positive likelihood ratio of 11.0 and a negative likelihood ratio of 0.14. The corresponding likelihood ratios for a previously derived probability threshold (0.1) were 6.84 and 0.09 for LR1, and 6.36 and 0.10 for LR2. On temporal validation (941 patients from seven centers), the AUCs were 0.945 (LR1), 0.918 (LR2) and 0.959 (subjective assessment). CONCLUSIONS: Both models provide excellent discrimination between benign and malignant masses. Because the models provide an objective and reasonably accurate risk estimation, they may improve the management of women with suspected ovarian pathology.
Assuntos
Neoplasias Ovarianas/diagnóstico por imagem , Neoplasias Pélvicas/diagnóstico por imagem , Doenças dos Anexos/diagnóstico por imagem , Adulto , Diagnóstico Diferencial , Feminino , Humanos , Modelos Logísticos , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Sensibilidade e Especificidade , Ultrassonografia DopplerRESUMO
BACKGROUND: The efficacy and tolerability of the regimen containing paclitaxel and cisplatin (TP) in the neo-adjuvant treatment of locally advanced squamous cell cervical cancer are unknown. The TIP regimen (TP plus ifosfamide) showed high efficacy but high toxicity and it is used as an internal control. PATIENTS AND METHODS: In all, 154 patients were randomized to TP (paclitaxel 175 mg/m(2) + cisplatin 75 mg/m(2); n = 80) or TIP (TP + ifosfamide 5 g/m(2); n = 74), three cycles, followed by radical surgery. Pathological response to chemotherapy was classified as optimal [no residual tumor (complete response) or residual disease with < or = 3 mm stromal invasion (PR1)] or suboptimal response. RESULTS: Patient characteristics (TP/TIP): stage IB2 (56%/64%), IIA (18%/14%), IIB (20%/19%), III-IVA (5%/4%) and median age (42 years/45 years). The optimal response rate in the TP group was 25%, 95% confidence interval (CI) = 16% to 37% and 43%, 95% CI = 31% to 55% in the TIP group. Grades 3-4 leukopenia (6%/53%) and neutropenia (26%/76%) were significantly more frequent on TIP. CONCLUSION: TP performance was below expectation since the lower 95% confidence limit of the optimal response rate failed to reach the prespecified minimum requirement of efficacy, i.e. 22%. The TIP regimen confirmed its activity but was associated with higher haematological toxicity than TP.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/cirurgia , Cisplatino/administração & dosagem , Paclitaxel/administração & dosagem , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/cirurgia , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Quimioterapia Adjuvante , Cisplatino/efeitos adversos , Terapia Combinada , Intervalo Livre de Doença , Feminino , Humanos , Ifosfamida/administração & dosagem , Ifosfamida/efeitos adversos , Pessoa de Meia-Idade , Paclitaxel/efeitos adversos , Taxoides/administração & dosagem , Taxoides/efeitos adversosRESUMO
OBJECTIVES: To determine the sensitivity and specificity of subjective evaluation of gray-scale and Doppler ultrasound findings (here called pattern recognition) when used by experienced ultrasound examiners with regard to making a specific diagnosis of adnexal masses. METHODS: Within the framework of a European multicenter study, the International Ovarian Tumor Analysis study, comprising nine ultrasound centers, women with at least one adnexal mass were examined with gray-scale and color Doppler ultrasonography by experienced ultrasound examiners. A standardized examination technique, and standardized terms and definitions were used. Using pattern recognition the examiners classified each mass as benign or malignant and suggested a specific diagnosis (e.g. dermoid cyst or endometrioma). The reference standard was the histology of the surgically removed adnexal tumors. RESULTS: A total of 1066 women were included, of whom 800 had a benign mass and 266 a malignant mass. A specific diagnosis based on ultrasound findings was suggested in 899 (84%) tumors. The specificity was high for all diagnoses (range, 94-100%). The sensitivity was highest for benign teratoma/dermoid cysts (86%, 100/116), hydrosalpinges (86%, 18/21), peritoneal pseudocysts (80%, 4/5) and endometriomas (77%, 153/199), and lowest for functional cysts (17%, 4/24), paraovarian/parasalpingeal cysts (14%, 3/21), benign rare tumors (11%, 1/9), adenofibromas (8%, 3/39), simple cysts (6%, 1/18) and struma ovarii (0%, 0/5). The positive and negative likelihood ratios of pattern recognition with regard to dermoid cysts, hydrosalpinges and endometriomas were 68.2 and 0.14, 38.9 and 0.15, and 33.3 and 0.24, respectively. Dermoid cysts, hydrosalpinges, functional cysts, paraovarian cysts, peritoneal pseudocysts, fibromas/fibrothecomas and simple cysts were never misdiagnosed as malignancies by the ultrasound examiner, whereas more than 10% of inflammatory processes, adenofibromas and rare benign tumors including struma ovarii were misdiagnosed as malignancies. CONCLUSIONS: Using subjective evaluation of gray-scale and Doppler ultrasound findings it is possible to make an almost conclusive diagnosis of a dermoid cyst, endometrioma and hydrosalpinx. Many other adnexal pathologies can be recognized but not confidently confirmed or excluded.
Assuntos
Doenças dos Anexos/diagnóstico por imagem , Competência Clínica/normas , Reconhecimento Automatizado de Padrão , Doenças dos Anexos/classificação , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/classificação , Neoplasias Ovarianas/diagnóstico por imagem , Valor Preditivo dos Testes , Prognóstico , Fatores de Risco , Sensibilidade e Especificidade , Ultrassonografia DopplerRESUMO
BACKGROUND: P63 belongs to the 'p53 family' whose role in cancer progression has been recently revisited in light of the plethora of splicing variants that are generated. We analyzed the expression of the full-length TAp63 gene and its dominant-negative form deltaNp63 in ovarian cancer biopsies to correlate their expression with clinical outcome. MATERIALS AND METHODS: Real-time RT-PCR analysis was used to determine the levels of TAp63 and deltaNp63 in 83 stage I and in 86 stage III ovarian cancer biopsies and in seven human ovarian cancer cell. RESULTS: TAp63 levels were comparable in stage I and stage III, but deltaNp63 levels increased 77-fold in stage III, independently of the p53 status. Patients with high deltaNp63 expression had the worst overall survival (OS); patients with a deltaNp63/TAp63 ratio >2 had a poor OS. Patients with a high deltaNp63/TAp63 ratio were those with a poor response to platinum-based therapy. CONCLUSIONS: Data indicate a role for deltaNp63 as a potential biomarker to predict patient's outcome and tumor progression in ovarian cancer. This would have particularly clinical relevance in ovarian cancer where the high rate of mortality reflects our lack of knowledge of molecular mechanisms underlying cell progression toward malignancy.
Assuntos
Biomarcadores Tumorais/análise , Proteínas de Ligação a DNA/análise , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/mortalidade , Transativadores/análise , Proteínas Supressoras de Tumor/análise , Biópsia , Progressão da Doença , Feminino , Humanos , Pessoa de Meia-Idade , Mutação , Estadiamento de Neoplasias , Neoplasias Ovarianas/patologia , Análise de Sobrevida , Fatores de TranscriçãoAssuntos
Doença Pulmonar Obstrutiva Crônica/terapia , Pneumologia/métodos , Respiração Artificial/métodos , Idoso , Dióxido de Carbono/metabolismo , Progressão da Doença , Feminino , Humanos , Troca Gasosa Pulmonar , Respiração , Respiração Artificial/efeitos adversos , Testes de Função Respiratória , Resultado do Tratamento , Ventiladores MecânicosRESUMO
Seven patients with advanced epithelial carcinoma and ascites, relapsing after two or more regimens of standard chemotherapy, have been treated with recombinant gamma-interferon (rIFN-gamma) i.p., via a permanent catheter. rIFN-gamma (Immuneron; Biogen; 0.5 mg = 10(7) IU in 2 liters of saline) was administered 3 times a week, on alternate weeks, for a total of nine courses. No major toxicities were observed: mild fever, malaise, and a flu-like syndrome occurred in all patients. The modulation of immunological parameters was studied. Cytotoxic activity of immunocompetent cells against tumor cell lines was measured both in the peritoneal compartment and in peripheral blood mononuclear cells. A significant increase of cytotoxicity of tumor-associated macrophages was observed in 5 of 7 patients and in 4 of 7 patients with tumor-associated peritoneal lymphocytes. Circulating effector cells were only occasionally stimulated. Tumor-associated macrophages isolated from the ascitic fluid and stimulated with lipopolysaccharide produced higher amounts of interleukin 1 in 5 of 6 patients tested, while interleukin 6 production by unstimulated tumor-associated macrophages was augmented in 2 of 2 patients after rIFN-gamma treatment. Freshly isolated ovarian carcinoma cells from the ascitic fluid has a variable, although usually low, expression of HLA-DR antigens. rIFN-gamma treatment caused a marked increase in HLA-DR expression in all patients tested. Expression of HLA class I antigens was negative in 2 of 5 patients and was strongly increased in 1 of the 2 after treatment. The observation that rIFN-gamma administered i.p. activates in situ effector cells and augments major histocompatibility antigen expression in tumor cells, with minimal toxicity, encourages further efforts to investigate its therapeutic potential in ovarian carcinoma.
Assuntos
Carcinoma/terapia , Interferon gama/uso terapêutico , Neoplasias Ovarianas/terapia , Ascite , Carcinoma/imunologia , Citocinas/biossíntese , Citotoxicidade Imunológica , Feminino , Antígenos HLA-D/metabolismo , Antígenos de Histocompatibilidade Classe I/metabolismo , Humanos , Imunidade Celular , Injeções Intraperitoneais , Interferon gama/administração & dosagem , Neoplasias Ovarianas/imunologia , Proteínas RecombinantesRESUMO
PURPOSE: Topotecan, a topoisomerase I inhibitor, was evaluated in a multicenter, phase II study of women with epithelial ovarian carcinoma who relapsed after one or two prior regimens that included platinum and paclitaxel. PATIENTS AND METHODS: Topotecan 1.5 mg/m2 daily was administered as a 30-minute infusion for 5 consecutive days on a 21-day cycle. Eligibility criteria included bidimensionally measurable disease, Eastern Cooperative Oncology Group performance status of 2 or less, and adequate bone marrow, liver, and renal function. Efficacy was assessed by independent radiologic review. RESULTS: One hundred thirty-nine patients were treated; 81% were platinum resistant. Sixty-two patients had received one prior regimen and 77 patients had received two prior regimens. Nine patients were not assessable for response; however, all patients were included in the response analysis. The overall response rate was 13.7%; 12.4% in platinum-resistant and 19.2% in platinum-sensitive patients. Stable disease lasted at least 8 weeks in 27.3% of the patients. The median duration of response and time to progression were 18.1 and 12.1 weeks, respectively. The median survival was 47.0 weeks. Grade 4 neutropenia occurred in 82% of the patients (34% of the courses) and thrombocytopenia in 30% of the patients (9% of the courses). Infectious complications occurred in 6% of the courses. Nonhematologic toxicities were mild. There were no drug-related toxic deaths. CONCLUSION: As a single agent, topotecan has modest activity in women with advanced epithelial ovarian carcinoma who have progressed or not responded after one or two prior regimens with platinum and paclitaxel. Further investigation of combination regimens is indicated in the primary therapy for ovarian cancer based on the mechanism of action and tolerability.
Assuntos
Antineoplásicos/uso terapêutico , Carcinoma/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Topotecan/uso terapêutico , Adulto , Idoso , Carboplatina/administração & dosagem , Carcinoma/patologia , Cisplatino/administração & dosagem , Esquema de Medicação , Feminino , Humanos , Leucopenia/induzido quimicamente , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Neutropenia/induzido quimicamente , Neoplasias Ovarianas/patologia , Paclitaxel/administração & dosagem , Trombocitopenia/induzido quimicamente , Resultado do TratamentoRESUMO
The effects of inspiratory flow and inflation volume on the mechanical properties of the respiratory system in eight sedated and paralyzed postoperative morbidly obese patients (aged 37.6 +/- 11.8 yr who had never smoked and had normal preoperative seated spirometry) were investigated by using the technique of rapid airway occlusion during constant-flow inflation. With the patients in the supine position, we measured the interrupter resistance (Rint,rs), which in humans probably reflects airway resistance, the "additional" resistance (delta Rrs) due to viscoelastic pressure dissipation and time-constant inequalities, and static respiratory elastance (Est,rs). Intra-abdominal pressure (IAP) was measured by using a bladder catheter, and functional residual capacity was measured by the heliumdilution technique. The results were compared with a previous study on 16 normal anesthetized paralyzed humans. Compared with normal persons, we found that in obese subjects: 1) functional residual capacity was markedly lower (0.645 +/- 0.208 liter) and IAP was higher (24 +/- 2.2 cmH2O); 2) alveolar-arterial oxygenation gradient was increased (178 +/- 59 mmHg); 3) the volume-pressure curve of the respiratory system was curvilinear with an "inflection" point; 4) Est,rs, Rint,rs, and delta Rrs were higher than normal (29.3 +/- 5.04 cmH2O/l, 5.9 +/- 2.4 cmH2O.l-1.s, and 6.4 +/- 1.6 cmH2O.l-1.s, respectively); 5) Rint,rs increased with increasing inspiratory flow, Est,rs did not change, and delta Rrs decreased progressively; and 6) with increasing inflation volume, Rint,rs and Est,rs decreased, whereas delta Rrs rose progressively. Overall, our data suggest that obese subjects during sedation and paralysis are characterized by hypoxemia and marked alterations of the mechanical properties of the respiratory system, largely explained by a reduction in lung volume due to the excessive unopposed IAP.
Assuntos
Obesidade/fisiopatologia , Paralisia/fisiopatologia , Respiração/fisiologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVES: To evaluate the role of needle aspiration in the management of endometriomas. DESIGN: Retrospective evaluation of the activity of the section of interventional ultrasound in a single tertiary care institution. SETTING: Department of Obstetrics and Gynecology, Ospedale S. Gerardo, Monza, University of Milan, Italy. PATIENTS: Two hundred nine premenopausal patients underwent aspiration for diagnostic purpose (n = 166), for relief of symptoms (n = 25), or with therapeutic intent (n = 18). RESULTS: Adequate material was obtained by all punctures. Early complications (self-limiting vagal symptoms or pain) occurred in eight cases. Short-term complications consisted of acute abdominal pain in three cases and infection in one. Three women required surgical treatment of the complication. At first examination after aspiration, persistence of the cyst was observed in all but four cases, including all cases who had undergone therapeutic aspiration. Nine patients reported relief of symptoms but six other patients referred onset or worsening of pelvic discomfort after aspiration. CONCLUSIONS: Ultrasound-guided aspiration of endometriomas is feasible. The transvaginal route reduces early complication but implies a risk of infection of 1.3%. However, drainage alone is ineffective as a therapeutic procedure and the applications of aspiration of endometriomas appear limited to some cases with diagnostic intent.