RESUMO
OBJECTIVE: Platinum-resistant epithelial ovarian cancer (EOC), recurrent endometrial cancer (EC), and triple negative breast cancer (TNBC) are difficult to treat after failing standard therapies. This phase I study evaluated mirvetuximab soravtansine (MIRV) and gemcitabine in patients with recurrent FRα-positive EOC, EC, or TNBC to determine the maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D) (primary endpoint). METHODS: FRα-positive patients with platinum-resistant EOC, EC, or TNBC with ≤4 prior chemotherapy regimens (2 for EC) were enrolled. FRα expression requirement varied among eligible tumors and changed during the study. RESULTS: Twenty patients were enrolled; 17 were evaluable for DLT. Half the patients received ≥3 prior chemotherapy lines. Most EOC and EC patients (78%) were medium (50-74%) or high(75-100%) FRα expressors. TNBC patients were low (25-49%) FRα expressors. The MTD/RP2D was MIRV 6 mg/kg AIBW D1 and gemcitabine 800 mg/m2 IV, D1 and D8, every 21 days (Dose Level [DL] 3), where 5/7 patients demonstrated a partial response (PR) as their best response, including 2 confirmed ovarian responses whose time-to-progression and duration of response were 7.9/5.4 and 8.0/5.7 months respectively. Most common treatment-related adverse events at MTD were anemia and neutropenia (3/7 each, 43%), diarrhea, hypophosphatemia, thrombocytopenia, and leukopenia (2/7 each, 29%). DLTs were thrombocytopenia (DL1), oral mucositis (DL4) and diarrhea (DL4). Nine of 20 patients (45%; 95% CI: 21.1-68.9%) achieved PR as their best response, with 3/20 patients or 15% (95%CI, 0-32.1%) confirmed PR. CONCLUSION: MIRV and gemcitabine demonstrate promising activity in platinum resistant EOC at RP2D, but frequent hematologic toxicities.
Assuntos
Anticorpos Monoclonais Humanizados , Neoplasias do Endométrio , Imunoconjugados , Maitansina , Neoplasias Ovarianas , Trombocitopenia , Neoplasias de Mama Triplo Negativas , Feminino , Humanos , Gencitabina , Neoplasias Ovarianas/patologia , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/etiologia , Tubas Uterinas/patologia , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/etiologia , Carcinoma Epitelial do Ovário/tratamento farmacológico , Carcinoma Epitelial do Ovário/etiologia , Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/etiologia , Diarreia/induzido quimicamente , Trombocitopenia/induzido quimicamente , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Maitansina/análogos & derivadosRESUMO
PURPOSE: Hyperthermic intraperitoneal chemotherapy (HIPEC) with cisplatin confers a survival benefit in epithelial ovarian cancer (EOC) but is associated with renal toxicity. Sodium thiosulfate (ST) is used for nephroprotection for HIPEC with cisplatin, but standard HIPEC practices vary. METHODS: A prospective, nonrandomized, clinical trial evaluated safety outcomes of HIPEC with cisplatin 75 mg/m2 during cytoreductive surgery (CRS) in patients with EOC (n = 34) and endometrial cancer (n = 6). Twenty-one patients received no ST (nST), and 19 received ST. Adverse events (AEs) were reported according to CTCAE v.5.0. Serum creatinine (Cr) was collected preoperatively and postoperatively (Days 5-8). Progression-free survival (PFS) was followed. Normal peritoneum was biopsied before and after HIPEC for whole transcriptomic sequencing to identify RNAseq signatures correlating with AEs. RESULTS: Forty patients had HIPEC at the time of interval or secondary CRS. Renal toxicities in the nST group were 33% any grade AE and 9% grade 3 AEs. The ST group demonstrated no renal AEs. Median postoperative Cr in the nST group was 1.1 mg/dL and 0.5 mg/dL in the ST group (p = 0.0001). Median change in Cr from preoperative to postoperative levels were + 53% (nST) compared with - 9.6% (ST) (p = 0.003). PFS did not differ between the ST and nST groups in primary or recurrent EOC patients. Renal AEs were associated with downregulation of metabolic pathways and upregulation of immune pathways. CONCLUSIONS: ST significantly reduces acute renal toxicity associated with HIPEC with cisplatin in ovarian cancer patients. As nephrotoxicity is high in HIPEC with cisplatin, nephroprotective agents should be considered.
Assuntos
Antineoplásicos , Hipertermia Induzida , Neoplasias Ovarianas , Humanos , Feminino , Cisplatino/uso terapêutico , Quimioterapia Intraperitoneal Hipertérmica , Antineoplásicos/uso terapêutico , Estudos Prospectivos , Hipertermia Induzida/efeitos adversos , Recidiva Local de Neoplasia , Neoplasias Ovarianas/patologia , Carcinoma Epitelial do Ovário , Procedimentos Cirúrgicos de Citorredução/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia CombinadaRESUMO
PURPOSE: Hyperthermic intraperitoneal chemotherapy (HIPEC) confers a survival benefit in epithelial ovarian cancer (EOC) and in preclinical models. However, the molecular changes induced by HIPEC have not been corroborated in humans. PATIENTS AND METHODS: A feasibility trial evaluated clinical and safety outcomes of HIPEC with cisplatin during optimal cytoreductive surgery (CRS) in patients with EOC diagnosed with stage III, IV, or recurrent EOC. Pre- and post-HIPEC biopsies were comprehensively profiled with genomic and transcriptomic sequencing to identify mutational and RNAseq signatures correlating with response; the tumor microenvironment was profiled to identify potential immune biomarkers; and transcriptional signatures of tumors and normal samples before and after HIPEC were compared to investigate HIPEC-induced acute transcriptional changes. RESULTS: Thirty-five patients had HIPEC at the time of optimal CRS; all patients had optimal CRS. The median progression-free survival (PFS) was 24.7 months for primary patients and 22.4 for recurrent patients. There were no grade 4 or 5 adverse events. Anemia was the most common grade 3 adverse event (43%). Hierarchical cluster analyses identified distinct transcriptomic signatures of good versus poor responders to HIPEC correlating with a PFS of 29.9 versus 7.3 months, respectively. Among good responders, significant HIPEC-induced molecular changes included immune pathway upregulation and DNA repair pathway downregulation. Within cancer islands, % programmed cell death protein 1 expression in CD8+ T cells significantly increased after HIPEC. An exceptional responder (PFS 58 months) demonstrated the highest programmed cell death protein 1 increase. Heat shock proteins comprised the top differentially upregulated genes in HIPEC-treated tumors. CONCLUSION: Distinct transcriptomic signatures identify responders to HIPEC, and preclinical model findings are confirmed for the first time in a human cohort.
Assuntos
Carcinoma Epitelial do Ovário , Quimioterapia Intraperitoneal Hipertérmica , Neoplasias Ovarianas , Carcinoma Epitelial do Ovário/tratamento farmacológico , Estudos de Viabilidade , Feminino , Humanos , Quimioterapia Intraperitoneal Hipertérmica/efeitos adversos , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Microambiente TumoralRESUMO
BACKGROUND: Part-time clinical nurse educators who simultaneously work in both a clinical and an academic setting experience a unique work-role transition. Identifying and addressing their needs during this time may assist in new faculty retention. PURPOSE: As part of a larger study examining the work-role transition of part-time clinical nurse faculty, a specific research question was developed to determine how these individuals experience the phases of the Nurse Educator Transition (NET) model. METHODS: This qualitative phenomenological study used both purposive and snowball sampling to recruit 14 RNs who were part-time clinical educators. RESULTS: Study findings validated all 4 phases of the NET model. In addition, several participants indicated a sense of returning to the first 2 phases of transition at the beginning of new semesters and courses. CONCLUSION: The NET model is applicable to the part-time clinical nurse educator population. This theory can be used as a framework to design orientation and mentorship programs that specifically target part-time clinical nurse educators.
Assuntos
Emprego/psicologia , Emprego/estatística & dados numéricos , Docentes de Enfermagem/psicologia , Docentes de Enfermagem/estatística & dados numéricos , Recursos Humanos de Enfermagem Hospitalar/educação , Recursos Humanos de Enfermagem Hospitalar/psicologia , Admissão e Escalonamento de Pessoal/estatística & dados numéricos , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Educacionais , Pesquisa em Educação em Enfermagem , Pesquisa Qualitativa , Estados UnidosRESUMO
AIM: The aim of this study was to explore how nurses experienced the role transition from clinical expert to part-time clinical faculty member when they worked in both a clinical and academic setting. BACKGROUND: In response to the current nurse faculty shortage and the anticipated return of a nationwide shortage of registered nurses, the use of part-time clinical nurse educators has been increasing. METHOD: Fourteen RNs were interviewed using online video conferencing for this qualitative phenomenological study. RESULTS: Study findings revealed seven key themes: different background-different experiences, guidance and support, challenges along the way, maintaining two work roles, influences of prior work experience, influence of personal attributes, and recommendations for successful transition. CONCLUSION: This work-role transition was found to be highly individualized and multifactorial. Results of the study may be beneficial in future administrative decision-making.
Assuntos
Mobilidade Ocupacional , Docentes de Enfermagem , Enfermeiras e Enfermeiros , Emprego , HumanosRESUMO
PURPOSE: To evaluate intraperitoneal (IP) nab-paclitaxel in patients with advanced malignancies that are primarily confined to the peritoneal cavity in a phase I trial. METHODS: Using a 3 + 3 dose escalation of IP nab-paclitaxel on days 1, 8, and 15 of a 28-day cycle, we evaluated six dose levels (35-175 mg/m2/dose). Maximum tolerated dose (MTD) and pharmacokinetics (PK) of IP nab-paclitaxel were determined. RESULTS: There were no dose-limiting toxicities (DLTs) in cohorts 1-3. There was a DLT in one of six patients in cohort 4 (112.5 mg/m2) (grade 3 neutropenia causing treatment delay > 15 days) and a DLT in one of three patients in cohort 6 (175 mg/m2) (grade 4 neutropenia and grade 3 abdominal pain). A second patient in cohort 6 experienced a serious adverse event (cycle 1, grade 4 ANC ≤ 7 days, cycle 4, grade 2 left ventricular dysfunction). This dose level was determined to be above the MTD. No DLTs were seen in seven patients treated in cohort 5 (140 mg/m2). The MTD of IP nab-paclitaxel was established at 140 mg/m2 on days 1, 8, and 15 of a 28-day cycle. There was a PK advantage for IP nab-paclitaxel, with an IP plasma area under the concentration-time curve (AUC) ratio of 147-fold (range 50-403) and therapeutic range systemic drug levels. Eight of 27 enrolled patients had progression-free survival ≥ 6 months. One patient experienced complete response, and one patient experienced partial response. Six patients had stable disease. CONCLUSIONS: Weekly IP nab-paclitaxel has a favorable toxicity profile, a significant pharmacologic advantage, and promising clinical activity. CLINICAL TRIAL REGISTRATION: NCT00825201.
Assuntos
Albuminas/administração & dosagem , Antineoplásicos Fitogênicos/administração & dosagem , Neutropenia/epidemiologia , Paclitaxel/administração & dosagem , Neoplasias Peritoneais/tratamento farmacológico , Adulto , Idoso , Albuminas/farmacocinética , Antineoplásicos Fitogênicos/farmacocinética , Área Sob a Curva , Estudos de Coortes , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Humanos , Infusões Parenterais , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neutropenia/induzido quimicamente , Neutropenia/diagnóstico , Paclitaxel/farmacocinética , Neoplasias Peritoneais/patologia , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
Vulvar cancer is a rare malignancy with high curability in early-stage disease, yet poor outcomes for advanced-stage and recurrent disease. Surgical management is at the cornerstone of treatment for most vulvar cancers, and includes conservative and radical resection of the primary vulvar tumor and excision of local lymph nodes, which are major prognostic factors and drive adjuvant treatment. This review summarizes the surgical management of primary squamous cell carcinoma of the vulva, specifically initial treatment guidelines by stage, based on the 2017 NCCN Clinical Practice Guidelines in Oncology for Vulvar Cancer.
Assuntos
Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Excisão de Linfonodo , Recidiva Local de Neoplasia/cirurgia , Neoplasias Vulvares/patologia , Neoplasias Vulvares/cirurgia , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/radioterapia , Feminino , Humanos , Canal Inguinal , Estadiamento de Neoplasias , Exenteração Pélvica , Guias de Prática Clínica como Assunto , Radioterapia Adjuvante , Fatores de Risco , Biópsia de Linfonodo Sentinela , Vulva/cirurgia , Neoplasias Vulvares/diagnóstico , Neoplasias Vulvares/radioterapiaRESUMO
Intraperitoneal chemotherapy poses both potential benefits as a cancer treatment and negative consequences on patient and family quality of life. The profound multi-dimensional quality of life impact of intraperitoneal (IP) chemotherapy upon women with advanced ovarian cancer makes the early integration of palliative care particularly important for this population. Numerous opportunities occur throughout the treatment process to improve the delivery of biopsychosocial-spiritual support to women receiving IP chemotherapy.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Ovarianas/terapia , Cuidados Paliativos , Qualidade de Vida , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , California , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Feminino , Humanos , Infusões Parenterais , Pessoa de Meia-Idade , Narração , Neoplasias Ovarianas/complicações , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/psicologia , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Pesquisa Qualitativa , Estudos RetrospectivosRESUMO
PURPOSE OF THE RESEARCH: Intraperitoneal (IP) chemotherapy is a viable and superior treatment to standard intravenous (IV) chemotherapy in women with small volume residual ovarian cancer following optimal debulking. Despite this clinical advantage, widespread adoption of the treatment regimen has been hampered by concerns related to toxicities and complications. The purpose of this descriptive study was to describe nursing implications related to toxicities, complications and clinical encounters in 17 women with ovarian cancer who received IP chemotherapy. METHODS AND SAMPLE: Women with ovarian cancer who received IP chemotherapy at one NCI-designated comprehensive cancer center were accrued. Data related to IP chemotherapy summary, clinical encounters and admissions were obtained through comprehensive chart audits. KEY RESULTS: Common treatment-related toxicities included nausea and vomiting, fatigue, hypomagnesia, pain, neuropathy, anemia, and constipation. Reasons for dose-modifications were multi-factorial, and were primarily related to catheter complications and chemotherapy toxicities. The number of clinical encounters was high, and they were primarily related to admissions for inpatient IP chemotherapy and follow-up clinic visits. CONCLUSIONS: Treatment-related toxicities and complications were common in women with ovarian cancer who received IP chemotherapy. Use of IP chemotherapy results in multiple clinical encounters, such as outpatient clinic visits and inpatient admissions. Nursing is a critical part of the interdisciplinary approach in caring for women treated with IP chemotherapy. Interdisciplinary teams with high levels of knowledge and skills related to IP chemotherapy administration are needed to manage treatment-related toxicities and complications, and support multiple clinical encounters during treatment.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/fisiopatologia , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/enfermagem , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Institutos de Câncer , Cateterismo/efeitos adversos , Cateterismo/métodos , Quimioterapia Adjuvante , Bases de Dados Factuais , Relação Dose-Resposta a Droga , Esquema de Medicação , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Feminino , Seguimentos , Humanos , Incidência , Injeções Intraperitoneais , Pessoa de Meia-Idade , Neoplasia Residual , Papel do Profissional de Enfermagem , Enfermagem Oncológica/métodos , Neoplasias Ovarianas/cirurgia , Ovariectomia/métodos , Estudos de Amostragem , Resultado do TratamentoRESUMO
OPINION STATEMENT: Nearly 500,000 new cases of cervical cancer and 274,000 cervical cancer deaths are occurring worldwide each year. Approximately 80% of the 500,000 new cases occur in developing countries and this percentage is expected to increase to 90% by 2020. In developing countries, cervical cancer tends to affect relatively young poor women and is the single largest cause of years of life lost to cancer, since screening and treatment programs, and health care, in general, are relatively inaccessible to these women. Each 5-year delay in vaccinating women against HPV may lead to the deaths of 1.5 to 2 million women from cervical cancer in developing countries. The high efficacy of the two available cervical cancer vaccines and their proven ability to reduce the incidence of cervical cancer precursor lesions offer hope that the vaccine will have enormous worldwide impact and may dramatically reduce the cervical cancer burden. The current vaccines protecting against HPV-16 and HPV-18 may prevent up to 70% of new cervical cancers. Vaccine cross-reactivity for HPV-31, -33, -45, and -52 suggest that an even higher percentage of cervical cancers might be prevented with its use. Currently, the prohibitive cost of the vaccine precludes its widespread implementation. Cooperation between governments, international health organizations, and the vaccine industry is needed to overcome this significant barrier so that women are no longer denied a potentially life-saving advance. Worldwide HPV vaccination and cervical cancer screening should be made an international priority.
Assuntos
Saúde Global , Vacinas contra Papillomavirus , Adolescente , Adulto , Alphapapillomavirus/imunologia , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Criança , Ensaios Clínicos como Assunto/estatística & dados numéricos , Custos e Análise de Custo , Reações Cruzadas , Países em Desenvolvimento/economia , Método Duplo-Cego , Feminino , Prioridades em Saúde , Acessibilidade aos Serviços de Saúde , Vacina Quadrivalente Recombinante contra HPV tipos 6, 11, 16, 18 , Humanos , Cooperação Internacional , Estudos Multicêntricos como Assunto , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/economia , Vacinas contra Papillomavirus/imunologia , Vacinas contra Papillomavirus/provisão & distribuição , Lesões Pré-Cancerosas/epidemiologia , Lesões Pré-Cancerosas/prevenção & controle , Lesões Pré-Cancerosas/virologia , Prevalência , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/prevenção & controle , Cervicite Uterina/epidemiologia , Cervicite Uterina/prevenção & controle , Cervicite Uterina/virologia , Vacinação/economia , Vacinação/estatística & dados numéricos , Adulto JovemRESUMO
We examined alterations in the p53 tumor suppressor gene and the ras and HER-2/neu oncogenes in chicken ovarian cancers to determine if these tumors have genetic alterations similar to those in human ovarian adenocarcinomas. Mutations in the p53 tumor suppressor gene and the H-ras and K-ras oncogenes were assessed by direct sequencing in 172 ovarian cancers obtained from 4-year-old birds enrolled at age 2 in two separate 2-year chemoprevention trials. Birds in trial B had approximately twice as many lifetime ovulations as those in trial A. Immunohistochemical staining for the HER-2/neu oncogene was done on a subset of avian ovarian and oviductal adenocarcinomas. Alterations in p53 were detected in 48% of chicken ovarian cancers. Incidence of p53 alterations varied according to the number of lifetime ovulations, ranging from 14% in trial A to 96% in trial B (P < 0.01). No mutations were seen in H-ras, and only 2 of 172 (1.2%) tumors had K-ras mutations. Significant HER-2/neu staining was noted in 10 of 19 ovarian adenocarcinomas but in only 1 of 17 oviductal adenocarcinomas. Similar to human ovarian cancers, p53 alterations are common in chicken ovarian adenocarcinomas and correlate with the number of lifetime ovulations. Ras mutations are rare, similar to high-grade human ovarian cancers. HER-2/neu overexpression is common and may represent a marker to exclude an oviductal origin in cancers involving both the ovary and oviduct.
Assuntos
Adenocarcinoma/genética , Genes ras/genética , Mutação/genética , Neoplasias Ovarianas/genética , Receptor ErbB-2/metabolismo , Proteína Supressora de Tumor p53/genética , Adenocarcinoma/patologia , Animais , Biomarcadores Tumorais/genética , Galinhas/genética , Galinhas/metabolismo , Modelos Animais de Doenças , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Técnicas Imunoenzimáticas , Neoplasias Ovarianas/patologia , Oviductos/metabolismo , Oviductos/patologia , Reação em Cadeia da PolimeraseRESUMO
Ovarian cancer is the fifth most common cause of cancer-related death among women in the United States, although the median survival of patients has been increasing over the past few decades. In patients with epithelial ovarian cancer, chemotherapy has increased survival. Platinum agents combined with taxanes have become standard treatment. Intraperitoneal chemotherapy has also increased survival. Cytoreductive surgery to optimally debulk a tumor or, ideally, remove any gross disease has also been shown to increase survival. Each 10% increase in cytoreduction correlates with a 5.5% increase in median survival. The ability to successfully perform optimal cytoreduction ranges from 20% to 90%. Many institutions have recently begun to perform aggressive/ultraradical procedures to achieve this result. Interval cytoreduction may also benefit patients whose initial surgery is suboptimal, especially if the first procedure was performed by a surgeon unfamiliar with the disease. Secondary cytoreduction can increase survival in patients with low-volume disease and a long disease-free interval. All of these procedures should be performed by a specialist trained in ovarian cancer surgery.
Assuntos
Procedimentos Cirúrgicos em Ginecologia/métodos , Neoplasia Residual , Neoplasias Epiteliais e Glandulares/cirurgia , Neoplasias Ovarianas/cirurgia , Feminino , HumanosRESUMO
Pathogenesis and growth of three common women's cancers (breast, endometrium and ovary) are linked to estrogen. A single gene encodes the key enzyme for estrogen biosynthesis named aromatase, inhibition of which effectively eliminates estrogen production in the entire body. Aromatase inhibitors successfully treat breast cancer, whereas their roles in endometrial and ovarian cancers are less clear. Ovary, testis, adipose tissue, skin, hypothalamus and placenta express aromatase normally, whereas breast, endometrial and ovarian cancers overexpress aromatase and produce local estrogen exerting paracrine and intracrine effects. Tissue-specific promoters distributed over a 93-kb regulatory region upstream of a common coding region alternatively control aromatase expression. A distinct set of transcription factors regulates each promoter in a signaling pathway- and tissue-specific manner. In cancers of breast, endometrium and ovary, aromatase expression is primarly regulated by increased activity of the proximally located promoter I.3/II region. Promoters I.3 and II lie 215 bp from each other and are coordinately stimulated by PGE(2) via a cAMP-PKA-dependent pathway. In breast adipose fibroblasts exposed to PGE(2) secreted by malignant epithelial cells, PKC is also activated, and this potentiates cAMP-PKA-dependent induction of aromatase. Thus, inflammatory substances such as PGE(2) may play important roles in inducing local production of estrogen that promotes tumor growth.
Assuntos
Aromatase/metabolismo , Neoplasias da Mama/enzimologia , Neoplasias do Endométrio/enzimologia , Regulação Enzimológica da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Neoplasias Ovarianas/enzimologia , Animais , Aromatase/genética , Neoplasias da Mama/genética , Neoplasias do Endométrio/genética , Feminino , Humanos , Neoplasias Ovarianas/genéticaRESUMO
In the United States, there are 11,150 cases and 3670 deaths projected due to invasive cervical cancer for 2007. Approximately 500,000 new cases and 274,000 deaths will occur in women throughout the world. Human papillomavirus (HPV) has been designated by the World Health Organization (WHO) as a "necessary cause" of cervical cancer. There are 6.2 million new cases of HPV diagnosed each year. In addition to cervical cancer, the virus has also been implicated in vaginal, vulvar, penile, anal, and head and neck cancers. Current methods for prevention of cervical cancer include Pap smears, HPV testing, ablative procedures, cervical conization, and hysterectomy. These are costly as well as invasive. The HPV vaccine is the most recent breakthrough for the prevention of cervical cancer. The quadrivalent HPV vaccine (Gardasil) covers types 6, 11, 16, & 18. The bivalent vaccine (Cervarix) covers types 16 & 18, and is expected to come out in the early part of 2007. Approximately 70% of cervical cancer is caused by HPV types 16 & 18. HPV types 6 &11 are responsible for 90% of anogenital warts. Females of ages 11-12 and those prior to their sexual debut should be vaccinated, with all females in the age range of 9-26 also eligible. This vaccination strategy can prevent the above HPV infections, cervical dysplasia, and possibly cervical cancer.
Assuntos
Alphapapillomavirus/efeitos dos fármacos , Infecções por Papillomavirus/tratamento farmacológico , Vacinas contra Papillomavirus/uso terapêutico , Neoplasias do Colo do Útero/prevenção & controle , Neoplasias do Colo do Útero/virologia , Feminino , Papillomavirus Humano 11/efeitos dos fármacos , Papillomavirus Humano 16/efeitos dos fármacos , Papillomavirus Humano 18/efeitos dos fármacos , Papillomavirus Humano 6/efeitos dos fármacos , Humanos , Masculino , Infecções por Papillomavirus/complicaçõesRESUMO
Vulvar cancer is an uncommon but devastating disease. In addition to radical vulvectomy, most patients require inguinofemoral lymphadenectomy, which often results in wound infection, wound breakdown, and chronic lymphedema. In the past, the gold standard for early lesions was radical vulvectomy with complete bilateral inguinal-femoral lymphadenectomy. This resulted in a low rate of recurrence but devastating disfigurement and high complication rates. Because only approximately 20% of patients with vulvar cancer have positive lymph nodes upon presentation, the traditional approach of inguinal-femoral lymphadenectomy for all patients resulted in many patients undergoing a morbid procedure without any real benefit. Sentinel node dissection, by removing only the nodes with the highest risk of containing metastases, offers a much less morbid alternative. In addition, because only one or two lymph nodes are removed, these can be subjected to a more thorough histopathologic analysis than conventional complete lymphadenectomy. This involves serial sectioning and immunohistochemical staining for cytokeratin antigen. Very small metastases, termed micrometastases, can be detected in this fashion. Therefore, sentinel node dissection with serial sectioning and immunohistochemical staining potentially offers a more accurate assessment of the regional nodes with less morbidity. Patients with positive sentinel nodes may then undergo additional therapy. Patients with negative sentinel nodes are theoretically at very low risk for metastases and should not require any additional treatment.
Assuntos
Biópsia de Linfonodo Sentinela/métodos , Neoplasias Vulvares/cirurgia , Feminino , Humanos , Excisão de Linfonodo/métodos , Metástase Linfática , Neoplasias Vulvares/patologiaRESUMO
This study meta-analytically examined extensive literature associated with work commitment. The primary purposes were to (a) cumulate correlations among dimensions of work commitment to see which were intercorrelated and (b) determine impact of work commitment dimensions and subdimensions on specific outcome variables (job satisfaction, job performance, turnover intentions, and turnover). Results were cumulated across 997 articles. The positive manifold of correlations suggests the presence of a common psychological construct underlying different commitment forms, with the exception of calculative, continuance, and union commitment. Most of the 94 meta-analyzed correlations were small, suggesting that concept redundancy is not a major concern. Meta-analyses of the correlations of 24 commitment constructs with 4 outcome variables suggest that different commitment forms have similar patterns of correlations with outcome variables.