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El objetivo es analizar los conceptos financieros que trabajamos para el cálculo de los pagos periódicos, así como, calcular los intereses y las tasas del crédito vehicular. Para realizar este estudio, se extrajo información de portales de inteligencia comercial, documentos bancarios, tesis y se visitó diferentes bancos ubicados en Lima metropolitana, de este modo, tuvimos conocimiento de primera mano sobre las diferentes opciones, modalidades, facilidades que nos presentan cada banco; con toda la información obtenida, presentamos aquí un cálculo de los pagos periódicos y tasas para los créditos vehiculares. The objective is to analyze the financial concepts that we work for the calculation of the periodic payments, as well as, to calculate the interest and the rates of the vehicular credit, in order to carry out this study, we extracted information from commercial intelligence portals, bank documents, theses and visited different banks located in metropolitan Lima, in this way, we had firsthand knowledge of the different options, modalities and facilities that we present each bank; with all the information obtained and we present here a calculation of the periodic payments and rates for vehicular credits.

BACKGROUND: Angiopoietin 1 and 2 regulate angiogenesis and vascular remodelling by interacting with the tyrosine kinase receptor Tie2, and inhibition of angiogenesis has shown promise in the treatment of ovarian cancer. We aimed to assess whether trebananib, a peptibody that inhibits binding of angiopoietin 1 and 2 to Tie2, improved progression-free survival when added to carboplatin and paclitaxel as first-line therapy in advanced epithelial ovarian, primary fallopian tube, or peritoneal cancer in a phase 3 clinical trial. METHODS: TRINOVA-3, a multicentre, multinational, phase 3, double-blind study, was done at 206 investigational sites (hospitals and cancer centres) in 14 countries. Eligible patients were aged 18 years or older with biopsy-confirmed International Federation of Gynecology and Obstetrics (FIGO) stage III to IV epithelial ovarian, primary peritoneal, or fallopian tube cancers, and an ECOG performance status of 0 or 1. Eligible patients were randomly assigned (2:1) using a permuted block method (block size of six patients) to receive six cycles of paclitaxel (175 mg/m2) and carboplatin (area under the serum concentration-time curve 5 or 6) every 3 weeks, plus weekly intravenous trebananib 15 mg/kg or placebo. Maintenance therapy with trebananib or placebo continued for up to 18 additional months. The primary endpoint was progression-free survival, as assessed by the investigators, in the intention-to-treat population. Safety analyses included patients who received at least one dose of study treatment. This trial is registered with ClinicalTrials.gov, number NCT01493505, and is complete. FINDINGS: Between Jan 30, 2012, and Feb 25, 2014, 1164 patients were screened and 1015 eligible patients were randomly allocated to treatment (678 to trebananib and 337 to placebo). After a median follow-up of 27·4 months (IQR 17·7-34·2), 626 patients had progression-free survival events (405 [60%] of 678 in the trebananib group and 221 [66%] of 337 in the placebo group). Median progression-free survival did not differ between the trebananib group (15·9 months [15·0-17·6]) and the placebo group (15·0 months [12·6-16·1]) groups (hazard ratio 0·93 [95% CI 0·79-1·09]; p=0·36). 512 (76%) of 675 patients in the trebananib group and 237 (71%) of 336 in the placebo group had grade 3 or worse treatment-emergent adverse events; of which the most common events were neutropenia (trebananib 238 [35%] vs placebo 126 [38%]) anaemia (76 [11%] vs 40 [12%]), and leucopenia (81 [12%] vs 35 [10%]). 269 (40%) patients in the trebananib group and 104 (31%) in the placebo group had serious adverse events. Two fatal adverse events in the trebananib group were considered related to trebananib, paclitaxel, and carboplatin (lung infection and neutropenic colitis); two were considered to be related to paclitaxel and carboplatin (general physical health deterioration and platelet count decreased). No treatment-related fatal adverse events occurred in the placebo group. INTERPRETATION: Trebananib plus carboplatin and paclitaxel did not improve progression-free survival as first-line treatment for advanced ovarian cancer. The combination of trebananib plus carboplatin and paclitaxel did not produce new safety signals. These results show that trebananib in combination with carboplatin and paclitaxel is minimally effective in this patient population. FUNDING: Amgen. ispartof: LANCET ONCOLOGY vol:20 issue:6 pages:862-876 ispartof: location:England status: published

La investigación profundiza en el conocimiento de la Alianza del Pacífico y explica con detalle los acuerdos comerciales que han adoptado sus miembros a fin de liberalizar el comercio de bienes y servicios en el bloque. Analiza estas medidas a la luz de las oportunidades comerciales que esta liberalización promete. La investigación establece que incluso considerando la baja interdependencia económica de los miembros de la Alianza del Pacífico y aun a pesar de que la integración económica al interior del bloque termina teniendo connotaciones más formales que reales; la posibilidad tangible de desarrollar cadenas productivas mirando a los mercados asiáticos exhibe a la Alianza del Pacífico como un mecanismo importante para conseguir tanto crecimiento económico como desarrollo social This paper explores the Pacific Alliance trying to explain the binding agreements that its members have adopted in order to liberalize the trade of goods and services within the block. It analyses these agreements, considering the potential trade opportunities that such a liberalization process promises. The research states that even considering the poor levels of economic interdependence among the members of the Pacific Alliance and despite the fact that economic integration inside the block has more formal than real connotations; the true chance of developing value chains for the Asian markets presents the Pacific Alliance as an important tool in order to obtain both economic growth and social development

Purpose To assess acute and late adverse events (AEs), overall survival (OS), pelvic failure (PF), regional failure, distant failure, and disease-free survival (DFS) in a prospective phase II clinical trial of bevacizumab (Bev) and pelvic intensity modulated radiation therapy (IMRT) with chemotherapy in high-risk endometrial-cancer patients.

Objective To identify problems at different treatment points (early treatment, mid-treatment, early posttreatment, and late posttreatment) among women with ovarian cancer. Design Longitudinal and cross-sectional study design. Setting An academic and community clinical cancer center in the Southeastern United States. Participants Sixty-eight women with Stage I to IV ovarian cancer. Methods Variables assessed included reported problems (physical, psychosocial, pain, marital, medical interaction), social support, optimism, and responses to open-ended questions. Analysis involved mixed models for longitudinal repeated measures and unpaired t tests and content analysis to describe responses to open-ended questions. Results Physical and psychosocial problems were greatest during early treatment and decreased throughout the treatment trajectory. Women with greater levels of social support and optimism at baseline had fewer problems over time. Women who did not have trouble paying for basics had fewer problems related to pain and psychological problems. Conclusion Problems across all domains must be addressed throughout the treatment trajectory, even after chemotherapy has ended. Nurses are well positioned to refer women appropriately to social workers and clinical navigators across all domains of care and should consider systematic assessment of patient-reported problems as a routine form of practice.

Purpose Intensity modulated radiation therapy (IMRT), compared with conventional 4-field treatment, can reduce the volume of bone marrow irradiated. Pelvic bone marrow sparing has produced a clinically significant reduction in hematologic toxicity (HT). This analysis investigated HT in Radiation Therapy Oncology Group (RTOG) 0418, a prospective study to test the feasibility of delivering postoperative IMRT for cervical and endometrial cancer in a multiinstitutional setting. Methods and Materials Patients in the RTOG 0418 study were treated with postoperative IMRT to 50.4 Gy to the pelvic lymphatics and vagina. Endometrial cancer patients received IMRT alone, whereas patients with cervical cancer received IMRT and weekly cisplatin (40 mg/m 2 ). Pelvic bone marrow was defined within the treatment field by using a computed tomography density-based autocontouring algorithm. The volume of bone marrow receiving 10, 20, 30, and 40 Gy and the median dose to bone marrow were correlated with HT, graded by Common Terminology Criteria for Adverse Events, version 3.0, criteria. Results Eighty-three patients were eligible for analysis (43 with endometrial cancer and 40 with cervical cancer). Patients with cervical cancer treated with weekly cisplatin and pelvic IMRT had grades 1-5 HT (23%, 33%, 25%, 0%, and 0% of patients, respectively). Among patients with cervical cancer, 83% received 5 or more cycles of cisplatin, and 90% received at least 4 cycles of cisplatin. The median percentage volume of bone marrow receiving 10, 20, 30, and 40 Gy in all 83 patients, respectively, was 96%, 84%, 61%, and 37%. Among cervical cancer patients with a V40 >37%, 75% had grade 2 or higher HT compared with 40% of patients with a V40 less than or equal to 37% ( P =.025). Cervical cancer patients with a median bone marrow dose of >34.2 Gy also had higher rates of grade ≥2 HT than did those with a dose of ≤34.2 Gy (74% vs 43%, P =.049). Conclusions Pelvic IMRT with weekly cisplatin is associated with low rates of HT and high rates of weekly cisplatin use. The volume of bone marrow receiving 40 Gy and the median dose to bone marrow correlated with higher rates of grade ≥2 toxicity among patients receiving weekly cisplatin (cervical cancer patients). Evaluation and limitation of the volume of bone marrow treated with pelvic IMRT is warranted in patients receiving concurrent chemotherapy.

PurposeThe objective of the study was to determine the impact of brachytherapy implant quality on outcome among cervical cancer patients treated on Radiation Therapy Oncology Group prospective trials 0116 and 0128.MethodsAll enrolled patients received concurrent chemoradiation followed by brachytherapy. Individual brachytherapy parameters, including the symmetry of ovoids in relation to the tandem, displacement of ovoids in relation to the cervical os, tandem bisecting the ovoids, tandem in the midpelvis, and appropriateness of packing, were scored for each implant. Multivariate Cox proportional hazards models were constructed for each parameter for local recurrence (LR), regional recurrence, distant recurrence, disease-free survival (DFS), and overall survival.ResultsRecords for 103 patients were analyzed. The median follow-up time was 24.5 months. Patients with unacceptable symmetry of ovoids to the tandem had a significantly higher risk of LR than patients in the acceptable group (hazard ratio [HR], 2.67; 95% confidence interval [CI], 1.11–6.45;P= 0.03). Patients with displacement of ovoids in relation to the cervical os had a significantly increased risk of LR (HR, 2.50; 95% CI, 1.05–5.93;P= 0.04) and a lower DFS rate (HR, 2.28; 95% CI, 1.18–4.41;P= 0.01). Inappropriate placement of packing resulted in a lower DFS rate (HR, 2.06; 95% CI, 1.08–3.92;P= 0.03).ConclusionsAssessment of the quality of a brachytherapy implant is imperative, as proper placement has an impact on patient DFS. If feasible, inappropriate placements should be corrected before treatment initiation. Brachytherapy applicators for cervical cancer should preferably be placed and assessed by experienced practitioners.

Background The objective of this study was to estimate antitumor activity and toxicity of weekly docetaxel and gemcitabine as second-line chemotherapy for patients with recurrent uterine carcinosarcoma. Methods Patients with recurrent carcinosarcoma of the uterus who had failed one regimen of chemotherapy, had a Gynecologic Oncology Group (GOG) performance status of 0–2 and had measurable disease were included. Treatment consisted of gemcitabine 600 mg/m2 and docetaxel 35 mg/m2 intravenously on days 1, 8 and 15 of a 28-day cycle until disease progression or intolerable adverse effects. This study employed an optimal but flexible two-stage design with an early stopping rule. If more than 3 out of 22–24 or more than 4 out of 25–29 patients responded, accrual to the second stage was to be initiated. Results Twenty-eight patients were enlisted. Three patients were not eligible after pathology review. One patient was never treated. Twenty-four patients were evaluable. Nine patients had previous radiation therapy. There were no complete responses. Partial responses were seen in two patients (8.3%), stable disease in eight (33.3%) and progressive disease in 12 patients (50%). Two patients were not evaluable (8.3%). The median progression-free survival was 1.8 months. The median survival was 4.9 months. The treatment caused myelosuppression, mainly neutropenia, but also thrombocytopenia and anemia. Dose modifications became necessary in the majority of patients. In five patients, treatment was discontinued due to toxicity. Conclusions This regimen of docetaxel and gemcitabine is not active in patients with recurrent carcinosarcoma of the uterus as second-line chemotherapy.

Findings from telephone focus groups have not been compared previously to findings from face-to-face focus groups. We conducted four telephone focus groups and five face-to-face focus groups in which a single moderator used the same open-ended questions and discussion facilitation techniques. This comparison was part of a larger study to gain a better understanding of employment experiences after diagnosis of gynecologic cancer. Offering the telephone option made it easier to recruit women from rural areas and geographically distant cities. Interaction between participants occurred in both types of focus group. Content analysis revealed that similar elements of the employment experience after cancer diagnosis were described by telephone and face-to-face participants. Participants disclosed certain emotionally sensitive experiences only in the telephone focus groups. Telephone focus groups provide useful data and can reduce logistical barriers to research participation. Visual anonymity might help some participants feel more comfortable discussing certain personal issues.

Introduction: An analysis of experience of surgical and gynecologic oncologists in the United States with the use of hyperthermic intraperitoneal chemotherapy for women with invasive epithelial ovarian cancer (EOC). Methods: An Internet-based registry (HYPER-O) collected data from collaborating institutions. Eligibility included women with EOC treated with hyperthermic intraperitoneal chemotherapy. Borderline and nonepithelial cancers were excluded. Results: As of July 1, 2008, 141 women were eligible for analysis treated at the following time points: frontline (n = 26), interval debulking (n = 19), consolidation (n = 12), and recurrence (n = 83). The mean perfusion temperatures were 38.5 to 43.6°C (median, 41.9°C) for inflow and 36.9 to 42.9°C (median, 41°C) for outflow for 30 to 120 minutes. Treatment was with a platinum agent (n = 72), mitomycin (n = 53), or a combination (n = 14). Median follow-up was 18 months (range, 0.3-140.5 months) and median overall survival 30.3 months (95% confidence interval, 23.0-37.6) with 2-, 5-, and 10-year overall survival probabilities of 49.1%, 25.4%, and 14.3%, respectively. Of the 141 patients, 110 (78%) experienced recurrence of ovarian cancer and 87 died, 3 (0.5%) dying within 30 days of surgery. In the multivariable analysis, the factors significant for increased survival were sensitivity to platinum response (P = 0.048), completeness of cytoreduction scores of 1 or 0 (P = 0.025), carboplatin alone or a combination of 2 or more chemotherapy agents used (P = 0.011), and duration of hospital stays of 10 days or less (P = 0.021). Conclusions: Hyperthermic intraperitoneal chemotherapy is a viable additional treatment option for patients with invasive EOC and may extend life in selected groups. It warrants further study in randomized controlled trials.

Most women with advanced ovarian cancer will relapse and subsequently develop platinum-resistant/refractory ovarian cancer. The benefit of treatment is currently based on objective response rates, which are a crude measure of benefit. It would be clinically meaningful if we were better able to measure the benefit of palliative therapy and, in particular, ascertain whether cancer-related symptoms improve with treatment and how this impacts on quality of life. This paper reviews the management of patients with platinum-resistant/refractory ovarian cancer and highlights the gaps in our knowledge and shortcomings with the current approaches to measure the benefit of treatment. The ultimate objective is to describe and encourage recruitment to the Gynecologic Cancer Intergroup study that has recently opened. This study will recruit a large number of patients from around the world in an effort to develop more robust instruments to measure the benefit of chemotherapy and to understand the impact of chemotherapy on symptom control and quality of life. In addition, this study will give us an insight into how all patients are managed rather than a select minority who are treated in clinical trials.

Purpose To determine the efficacy and patterns of initial failure for oral celecoxib, intravenous cisplatin, and 5-fluorouracil and concurrent pelvic radiotherapy in patients with locally advanced cancer of the cervix. Methods and Materials Patients were treated with concurrent 5-fluorouracil and cisplatin chemotherapy and pelvic radiotherapy and brachytherapy. Celecoxib was prescribed at a dose of 400 mg twice daily for 1 year beginning on the first day of radiotherapy. The overall and disease-free survival rates were determined. Results A total of 84 patients were accrued, of whom 78 were eligible. The estimated 2-year disease-free survival and overall survival rate was 69% and 83%, respectively. Of the 78 patients, 24 had treatment failure: 3 with persistent local disease, 9 local only, 2 regional, 4 distant, 1 regional and distant, 1 local and distant, and 2 with local, regional, and distant disease, and 1 had died of cervical cancer without a reported site of first failure and 1 without evidence of disease. Conclusion At 2 years, the estimated disease-free survival and overall survival rate for patients with advanced cervical cancer who underwent a combination of chemoradiotherapy and celecoxib treatment was 69% and 83%, respectively. Recurrent disease developed in 24 patients, and, of those patients, 18 had a component of locoregional failure as a site of first failure. Thus, locoregional control continues to be problematic after chemoradiotherapy as delivered in our study. The identification of more active biologically targeted therapies is warranted for the treatment of advanced cancer of the cervix.

Objectives. The progression of chemotherapy-resistant cancer confers poor prognosis and decreases overall survival in ovarian cancer patients. Adjuvants to traditional chemotherapy regimens have become attractive modalities for the clinical treatment of refractory or resistant ovarian cancer. We evaluated whether the addition of NSAID to hyperthermic chemotherapy would increase cytotoxicity in cisplatin- and taxane-treated ovarian cancer cells. Methods. Western blot analysis was utilized to determine COX-2 protein expression levels in the 2008, cisplatin-sensitive, and C13 ⁎ , cisplatin-resistant, cell lines. PGE 2 levels were determined and analyzed as a function of cyclooxygenase activity by LC/MS/MS. Cells were treated with cisplatin, docetaxel or paclitaxel in combination with either NS-398 or sulindac sulfide at 37°C, 41°C or 43°C. Cell viability was determined by a MTS cell proliferation assay. Results. Both cell lines expressed COX-2 protein, and NS-398 and sulindac sulfide effectively blocked PGE 2 production. The addition of a NSAID to cisplatin treatment in 2008 and C13 ⁎ cells offered enhanced cytotoxicity and this effect was further enhanced at 41°C. In docetaxel-treated 2008 cells, both NS-398 and sulindac sulfide offered enhanced cell kill; however, this result was not observed in paclitaxel-treated cells. Hyperthermia appeared to play no additional role in taxane cytotoxicity enhancement, however no antagonism was detected. Conclusions. Our results suggest that the combination treatment (cisplatin or docetaxel in combination with NSAID) cause a dose-dependent enhancement of cytotoxicity. Hyperthermia may improve the results of intraperitoneal cisplatin therapy, thus warranting further evaluation in clinical studies.

It was hypothesized that music or guided imagery versus usual care would result in less anxiety and perceived pain for colposcopy patients.Patients were randomized to music, guided imagery, or usual care after completing a baseline questionnaire. All patients completed a postprocedure questionnaire.Study participants (N=170) had a mean age of 28.4 years (SD=9.6; range 18-60) and formed a racially diverse group. Education/income levels were low. No between-group differences were found for postprocedure anxiety or pain rating.Mind-body interventions had no statistically significant impact on reported anxiety, perceived pain, or satisfaction with care, even for those who anticipated the most pain or started with high anxiety.

Purpose: To determine treatment-related acute toxicity rates in patients with locally advanced cervical cancer treated by oral celecoxib, i.v. cisplatin and 5-FU, and concurrent pelvic radiation therapy. Methods and Materials: Eligible patients on this RTOG Phase I-II study for advanced cervix cancer included FIGO Stage IIB-IVA or patients with FIGO Stage IB through IIA with biopsy proven pelvic node metastases or tumor size ≥5 cm. Patients were treated with pelvic radiotherapy and brachytherapy. Celecoxib was prescribed at 400 mg twice daily beginning on day 1 for 1 year. Cisplatin (75 mg/m2) and 5-FU (1g/m2 for 4 days) were administered every 3 weeks times 3. The primary end point of the study was treatment related toxicity. Results: Between August 2001 and March 2004, 84 patients were accrued to the study and 77 patients were evaluable for toxicity. Regarding the primary end point, toxicities were observed in the following areas: blood/bone marrow (16), gastrointestinal (14), pain (7), renal/genitourinary (6), cardiovascular (3), hemorrhage (1), and neurologic (1). For the first 75 evaluable patients, a toxicity failure was identified in 36 patients for a rate of 48%. Conclusions: Celecoxib at 400 mg twice daily together with concurrent cisplatin and 5-FU and pelvic radiotherapy has a high incidence of acute toxicities. The most frequent toxicities were hematologic. Albeit, the toxicity was deemed excessive in this trial, the rate of toxicities was not too different compared to other recent experiences with concurrent chemoradiation for advanced cervix cancer.

Objective To summarize the literature on options of management of patients treated for locally advanced cervical cancers with a specific focus on resource-constrained settings where brachytherapy is not available. Materials and methods A Medline search was performed to summarize studies about treatment approaches including neoadjuvant chemotherapy, primary surgery for bulky cervical cancer, and chemoradiation followed by surgery. Summaries are by treatment approaches that are relevant to resource-constrained settings. Results There are a lack of studies performed on neoadjuvant chemotherapy in low-resource settings. Primary surgery followed by chemoradiation therapy for selected patients with bulky cervical cancer is a feasible option. The disadvantage is the potential increase in treatment complications. Chemoradiation without brachytherapy followed by surgery has been found to have equivalent outcomes and is associated with acceptable morbidity. Conclusions In resource-constrained settings where brachytherapy is not available, performing radical hysterectomy after chemoradiation therapy without brachytherapy has been shown to produce equivalent outcomes. It seems reasonable to adopt a modified therapeutic protocol of chemoradiation followed by extrafascial hysterectomy as an alternative treatment option in low-resource countries where brachytherapy is not readily available.

Here we report our combined analysis of vaginal mesonephric adenocarcinoma (MA) in a 13 years old treated at our institution and of reported vaginal or cervical MA and clear-cell adenocarcinoma in 37 patients 18 years old or younger. Tumors in 27 patients arose in the vagina; 8 (21%) had metastases at diagnosis. The predominant symptom was vaginal bleeding; 62% of patients were exposed to diethylstilbestrol in utero. The 3-year survival estimate was 71% +/- 11%. Surgical treatment and metastasis at diagnosis were significant predictors of survival. The association between tumor excision and excellent outcome suggests that radical hysterectomy or pelvic exenteration is unnecessary. Radiotherapy as an adjunct may have contributed to this outcome.

Objective. The objective of this study was to determine the health-related quality of life (QOL) of disease-free patients after therapy for gynecologic malignancies at follow-up in an outpatient clinic. Methods. Eighty-five patients (P) completed the general Functional Assessment of Cancer Therapy (FACT-G) QOL questionnaire at least 6 months after treatment for a gynecologic malignancy. Responses were compared to 42 unmatched healthy women (H) who were seen for standard gynecologic screening exams. Statistical evaluation was done using t tests, χ 2 ,and Wilcoxon rank-sum tests, Spearman rank correlations, and linear regression. Results. The demographic data for the groups were as follows: median age P, 59 years; H, 56 years; Caucasian P, 51%; H, 56%, African American P, 49%; H, 44%, cervix cancer ( n = 51, 60%), uterine cancer ( n = 24, 28%), ovarian cancer ( n = 10, 12%). The median time since therapy was 39 months (range 6–149 months). There were no overall differences in FACT-G scores of patients and healthy women. Cancer survivors scored slightly higher on the emotional well-being subscale (mean 20.4 vs 19.2). Among cancer patients, all scores were lowest in patients with ovarian cancer. Longer treatment time was associated with a lower physical well-being. Older patients scored higher on emotional well-being, but lower on social/family well-being. Poor education and no help at home were associated with lower functional well-being and total FACT scores. Linear regression analysis revealed significantly lower total QOL scores in patients with the following characteristics: ovarian cancer diagnosis, treatment with radiation therapy or multi-modality therapy, less than high school education, and lack of help at home. Conclusion. Overall the recovery from treatment for gynecological cancer is good. Patients with ovarian cancer, prolonged therapy, poor education, and little social support have the most significant impairments in health-related quality of life and need additional support resources.

The objective of this study was to determine if breast cancer risk assessment following the Gail model should be incorporated into a gynecologic oncology clinic. The Gail model was used to assess the risk of breast cancer in 329 patients with preinvasive lower genital tract disease (Pre, n = 86), invasive vulvar and cervical (Cx, n = 102), uterine (Ut, n = 87), and ovarian cancer (Ov, n = 54) seen in an inner city gynecologic oncology office. T-test, chi square test, and Pearson and Spearman correlation coefficients were used for statistical evaluation. A P-value of less than 0.05 was regarded significant. An estimated 5-year risk of breast cancer of 1.67 or more was noted in 9% of the Pre patients, 5% of Cx patients, 21% of the Ut patients, and 9% of the Ov patients. The difference between Cx and Ut patients was significant. The average 5-year risk was calculated at 0.77 for Pre patients, 0.77 for Cx patients, 1.18 for Ut patients, and 1.11 for Ov patients. These differences were significant, but mirror the age distribution. The average age was 43.6 for Pre patients, 52.2 years for Cx, 61.5 years for Ut, and 58.5 years for Ov patients; these differences were significant. When calculations were corrected for the mean age (53 years), there were no significant differences between groups regarding the average risk: Pre: 1.04, Cx: 0.81, Ut: 0.96, Ov: 0.97. Only eight patients (2.4%), six of them in the Pre and Cx group, would be expected to derive significant benefit from tamoxifen therapy. We conclude that elevated 5-year breast cancer risk to 1.67% or higher is noted in about 11% of patients seen in a gynecologic oncology office, mainly related to age and family history. Risk assessment and regular screening should be part of any follow-up exam.

Study Objectives . To use Chlamydia trachomatis immunoglobulin-γ (IgG) titers to investigate the possibility of their association with ovarian cancer, and to evaluate the effectiveness of this titer in algorithmic protocols in infertility. Design . Prospective, age-matched, pilot study (Canadian Task Force classification II-2). Setting . University and university-affiliated office practice. Patients . The original 30 patients were seen for follow-up of ovarian cancer (19) and at yearly examination for nonmalignant disease (10). An additional group of 21 women seen for pelvic pain and infertility was added to clarify questions that arose during the study. Interventions . None. Measurements and Main Results . Chlamydia trachomatis IgG titers were positive in 15 (79%) of 19 of women with ovarian cancer, 9 (90%) of 10 age-matched controls, and 14 (67%) of 21 patients with infertility and pain. When analyzed by age, 4 (40%) of 10 patients under 30 years and 34 (85%) of 40 patients 30 years of age or older had positive titers (p=0.007). Of 21 women with positive Chlamydia pneumoniae titers, 17 (81%) had positive C. trachomatis titers, and 17 (85%) of 20 with positive C. trachomatis titers had positive C. pneumoniae titers. Conclusion . The test kit used in this study may not be adequate in older patients due to cross-reaction with C. pneumoniae titers. Further evaluation of C. trachomatis IgG titers as a marker in the study of ovarian cancer will require titers that are more specific than those we used. Although these titers may be useful as an immunologic screening marker in infertile patients, results should be interpreted with caution. A positive test may not be evidence of C. trachomatis infection and is not an indication for specific therapy. Successful use of some currently available C. trachomatis IgG titers in algorithms for infertility may be related to a patient's age.

Colon cancer with a synchronous ovarian metastasis is occasionally diagnosed at the time of laparotomy for a pelvic mass. The purpose of this retrospective study is to evaluate the clinical presentation as well as the impact of the type of metastatic spread and surgical intervention on overall survival. We reviewed charts of 23 patients treated between 1980 and 1995. Pain was the initial symptom in 14 patients (61%), with only four patients (17%) complaining of rectal bleeding, but with five patients (22%) complaining of uterine bleeding. At the time of laparotomy, the ovarian capsule was intact in 12 patients. Metastatic disease to the peritoneum was seen in seven patients and to the liver in six patients. On pathological evaluation, the median ovarian tumor size was 10 cm, significantly larger than the median colon tumor size of 4.5 cm. Surgical treatment consisted of colon resection in all but one patient, bilateral or unilateral salpingo-oophorectomy in 22 patients, and hysterectomy in nine patients. Only one patient survived 5 years. Sixteen patients died of colon cancer. The median survival time was 17.8 months, ranging from 1 to 86 months. Tumor size was of no prognostic importance. Median survival time of patients with peritoneal disease (10.8 months) was significantly shorter compared to patients without peritoneal disease (25.2 months). In the presence of liver metastasis, the median survival time was, likewise, significantly reduced from 20.1 months to 8.1 months. In conclusion, macroscopic metastatic disease to the ovary is a poor prognostic factor in colon cancer. In selected patients who can be rendered disease-free by surgery, prolonged survival is possible and an aggressive approach is recommended. Survival of patients with peritoneal disease or liver metastasis is short and a mainly palliative approach is recommended.

Arguments in support of and against routine screening for psychological distress, including depression, and sexual dysfunction among women with gynecologic cancer are considered. Proponents of universal screening note the high prevalence of distress and the options for successful treatment of such distress if detected. Patient-initiated or oncologist-determined detection of distress, however, is highly unreliable and the distress of many patients goes unrecognized. Routine use of self-report screening instruments to rapidly and prospectively identify those patients who are struggling with the challenges of cancer diagnosis and treatment is promoted as the most efficient solution to providing equitable access to psychosocial and mental health care in oncology settings. Critics of universal screening point to the absence of data on the practical utility of screening and provide evidence suggesting that screening is an inefficient method of improving patient well-being. Systematic evidence demonstrating the benefits of screening for distress in general or depression specifically are lacking. Potential harms of screening have not been considered. We conclude that stronger, high-level evidence demonstrating that routine screening results in better outcomes is needed before such programs will or should be broadly adopted. In relation to screening for sexual dysfunction, the situation is not much different. Sexual dysfunction is frequent among survivors of gynecologic cancer and is related to emotional changes, as well as physical changes in vaginal function and hormone status, mainly premature menopause. The effects in some patients significantly impair quality of life for years. Patients and physicians are often reluctant to discuss these issues openly; therefore a screening questionnaire would be of benefit to select patients who need further evaluation and treatment. A variety of treatment options have been described. Unfortunately, there is no consensus regarding the best questionnaire to use; reports in the literature often contain only a limited number of patients with various malignancies in different stages of survival, and there are very few randomized studies evaluating treatment outcomes. In addition, only limited resources are available. For these reasons, we conclude that at this time, universal screening cannot be recommended. More research is definitely needed; however, we still encourage physicians to at least ask their patients about sexual function.

PurposeThis study aimed to measure expression of cyclooxygenase-2 (COX-2) and CD34 in pretreatment tumor biopsies from patients on the RTOG C0128 phase II study, and to correlate expression of these biomarkers, using quantitative immunohistochemistry, with clinical outcome parameters.Methods and MaterialsPretreatment biopsies were placed into tissue microarrays. COX-2 and CD34 expression were measured using automated quantitative immunohistochemistry (AQUA®). Cox regression models and Fisher’s exact test were used to explore associations between expression of the biomarkers and clinical end points.ResultsEighty-four patients were accrued between 2001 and 2004; 78 were eligible and analyzable. Pathology specimen submission was optional; COX-2 expression was determined for 37 (47%) of patients, and CD34 scoring was determined for 34 (44%) of patients. Median follow-up was 44.5 months. In tumors where COX-2 data were available, 6 (16%) of 37 patients had local-regional failure; 4 of these patients had tumors with COX-2 scores below the AQUA® score median (hazard ratio, 0.39; 95% confidence interval, 0.07–2.16;P= 0.28). Of the 8 patients with disease-free survival failures, 5 had tumors with COX-2 levels below the median (hazard ratio, 0.49; 95% confidence interval, 0.12–2.04;P= 0.32). The 4 patients who died all had COX-2 levels below the median value. COX-2 levels below the median were associated with worse 2-year survival (Fisher’sP= 0.046). There was no statistically significant association between CD34 status and clinical outcome.ConclusionsLow COX-2 expression measured by AQUA® was associated with worse overall survival in this subset of patients available for analysis from RTOG C0128. Application of AQUA® technology, in a larger study, will be required to definitively evaluate the association COX-2 with clinical outcome in cervical cancer.

Twenty-one patients who underwent pelvic exenteration for primary ( n = 8) or recurrent ( n = 13) vulvar malignancy at the M. D. Anderson Cancer Center between 1956 and 1989 were evaluated. A posterior exenteration was performed in 12 patients, anterior exenteration was performed in 6, and total exenteration was performed in 3. In patients with primary tumors, radical vulvectomy and inguinal lymphadenectomy were also performed. The median patient age was 57 years. The mean tumor diameters were 5 cm (primary) and 4 cm (recurrent). Infections were the most frequent postoperative complications ( n = 15), followed by pulmonary ( n = 4) and cardiac problems ( n = 3). There were no treatment-related deaths. Five patients required further surgery to correct late postoperative sequelae. Four of eight patients experienced recurrence after treatment of their primary tumor; the recurrences were local only ( n = 1), in the inguinal area ( n = 2), or local and in the pelvis ( n = 1). Nine of the 13 patients treated for recurrent tumors developed a second recurrence; the second recurrences were all within the pelvis, although two also had a distant component. The 5-year survival rates were 70% for patients treated for primary disease and 38% for patients treated for recurrent disease, Pelvic exenteration is indicated for selected patients with advanced vulvar malignancy.

Uterine papillary serous adenocarcinoma (UPSC) is one of the most aggressive endometrial tumors. UPSC has been associated with an increased propensity for extrauterine spread. Survival rates of not more than 50% are commonly reported even for tumors which appear to be confined to the uterus. Small areas of UPSC can be found in otherwise well-differentiated endometrial lesions and yet still determine the overall prognosis. In the present study we evaluated histologic criteria that might be helpful in diagnosing small-volume UPSC, including silver-stained nucleolar organizer regions (AgNOR) which have prognostic importance in a variety of tumors, and nuclear size which has been used for prognostication in endometrial cancer. We examined 25 UPSC specimens and compared them to grade III (GIII, n = 10) and grade I (GI, n = 10) typical endometrial adenocarcinoma using the following parameters: mean AgNOR count per cell was UPSC 6, GIII 6.0, and GI 4.3; mean AgNOR area was UPSC 1.28 microns2, GIII 1.35 microns2, and GI 0.86 microns2; total AgNOR area per cell was UPSC 7.5 microns2, GIII 8.13 microns2, GI 4.47 microns2; and nuclear size was UPSC 66.9 microns2, GIII 60.3 microns2, GI 34.8 microns2. All differences between UPSC or GIII tumors and GI lesions were statistically significant. Overexpression of p53, as determined histochemically, was seen in 64% of the UPSC specimens. UPSC is characterized by high AgNOR count and area per cell, large nuclear size, and a high rate of p53 overexpression. Evaluation of these parameters in biopsy material may aid in selecting high-risk patients for adjuvant therapy trials.

Objective To correlate Chlamydia trachomatis immunoglobulin gamma (IgG) titers with psammoma bodies, dystrophic peritoneal calcification, degree of calcification, adhesions, and hydrosalpinges. Design This is a prospective single-blinded histologic analysis of tissue and retrospective analysis of historical laboratory and clinical variables. Setting Tertiary hospital and private practice patient charts. Patients Sixty consecutive patients with C. trachomatis IgG titers reported on the coding sheets of a previous study for endometriosis. Main Outcome Measures The histologic slides were reviewed in a blinded fashion for calcification. Previously used data sheets were reviewed for C. trachomatis IgG titers. Historical data, adhesion scores, hystrosalpingogram findings, and laparoscopic findings were obtained from charts. Results Dystrophic calcification, psammoma bodies, moderate-to-severe dystrophic calcification and hydrosalpinges were associated with positive C. trachomatis IgG titers. Conclusion This study suggests relationship of C. trachomatis with dystrophic calcification, psammoma bodies, adhesions, and hydrosalpinges. This relationship suggests that C. trachomatis IgG titers can be used as a marker to help determine those infertility patients who might best benefit from hysterosalpingogram or laparoscopy and in clinical studies of endometriosis, infertility, pain, or ovarian cancer. However, there is no current data to suggest a need for therapy on the basis of a positive C. trachomatis IgG titer or of dystrophic peritoneal calcification.

Background Nucleolar organizer regions (AgNORs) are associated with proliferative activity and ploidy in many tumors. The endocervical growth pattern of cervical adenocarcinoma renders tumor volume assessment more difficult, necessitating additional prognostic indicators. Methods Thirty-five cases of cervical adenocarcinoma were evaluated by reviewing charts and histologic sections. Nucleolar organizer regions were stained and counted manually; the mean number per cell and the percentage of cells with more than 5 AgNORs were recorded. Ploidy and S-phase fraction were determined by flow cytometry. Results Mean AgNOR counts per cell were significantly higher in adenocarcinoma (3.0) and adenosquamous carcinoma (4.3) than in benign endocervical epithelium (1.4). Grade 3 tumors had higher values (4.0) than Grade 1 lesions (2.9), and tumors with lymphovascular space involvement had higher values (3.5) than tumors without such involvement (2.7). No significant correlation was seen with regard to tumor stage or size. Flow cytometric parameters did not correlate with any of the examined parameters, although the DNA index was higher in larger tumors. Correlation between AgNOR counts and flow cytometry was significant only in Grade I tumors. Conclusions Nucleolar organizer region counts correlated better with histologic parameters of cervical adenocarcinoma than did flow cytometry. Because it is easily performed and does not require sophisticated equipment, AgNOR counts should be investigated further in a larger group of patients to determine their prognostic value.

Nucleolar organizer regions, which are evaluated using a silver stain for paraffin-embedded sections (AgNOR), can be used as a measurement of cellular proliferative activity. In the endometrium significant differences have been seen between benign and malignant lesions. To determine if AgNOR counts are of prognostic value in endometrial cancer, we examined 28 patients who developed recurrent disease after surgical stage Ib and Ic endometrial cancer and compared this group with a matched control group of patients who did not develop recurrence. The mean AgNOR number per cell was significantly higher in patients with recurrent disease (P = 0.001). Only five of these patients had values less than 4, whereas only three of the control group had values higher than 4. There was also a significant difference in the percentage of cells with more than 5 and more than 8 AgNORs (P = 0.001). After radiation therapy, the number of AgNORs per cell decreased. Recurrent tumors had higher AgNOR counts than the respective primary tumors. In conclusion, patients at increased risk for recurrent endometrial cancer can be identified by high AgNOR counts. Further evaluation of this parameter and comparison to other prognostic factors seems warranted.

We determined whether mutations in p53 exons 5–6–7–8, as detected in the polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) test, might be correlated with stage or grade in endomttrial adenocarcinoma. We amplified sequences containing exons 5, 6, 7, or 8 in DNA from tumors and controls. Mttation within the amplified sequences was indicated by changes in electrophoretic mobility (band shifts) in the SSCP test. The results were analyzed statistically and compared with the results of other, similar studies. We identified 15 band shifts among 47 endomttrial tumors studied (band shifts in two different exons in two cases) and none among 42 controls. Band shifts in exons 5 and 8 were associated uniformly with grade 2 or grade 3 histology. In other studies p53 mutations were correlated with advanced-stage malignancy. Further evaluation of particular p53 mutations and their relation to disease course in endomttrial adenocarcinoma seems warranted. The PCR-SSCP test seems well-suited to this purpose.

Purpose To determine the feasibility of pelvic intensity modulated radiation therapy (IMRT) for patients with endometrial cancer in a multi-institutional setting and to determine whether this treatment is associated with fewer short-term bowel adverse events than standard radiation therapy. Methods Patients with adenocarcinoma of the endometrium treated with pelvic radiation therapy alone were eligible. Guidelines for target definition and delineation, dose prescription, and dose-volume constraints for the targets and critical normal structures were detailed in the study protocol and a web-based atlas. Results Fifty-eight patients were accrued by 25 institutions; 43 were eligible for analysis. Forty-two patients (98%) had an acceptable IMRT plan; 1 had an unacceptable variation from the prescribed dose to the nodal planning target volume. The proportions of cases in which doses to critical normal structures exceeded protocol criteria were as follows: bladder, 67%; rectum, 76%; bowel, 17%; and femoral heads, 33%. Twelve patients (28%) developed grade ≥2 short-term bowel adverse events. Conclusions Pelvic IMRT for endometrial cancer is feasible across multiple institutions with use of a detailed protocol and centralized quality assurance (QA). For future trials, contouring of vaginal and nodal tissue will need continued monitoring with good QA and better definitions will be needed for organs at risk.

The 4th Ovarian Cancer Consensus Conference of the Gynecologic Cancer InterGroup was held in Vancouver, Canada, in June 2010. Representatives of 23 cooperative research groups studying gynecologic cancers gathered to establish international consensus on issues critical to the conduct of large randomized trials. Group C, 1 of the 3 discussion groups, examined recurrent ovarian cancer, and we report the consensus reached regarding 4 questions. These included the following: (1) What is the role of cytoreductive surgery for recurrent ovarian cancer? (2) How do we define distinct patient populations in need of specific therapeutic approaches? (3) Should end points for trials with recurrent disease vary from those of first-line trials? (4) Is CA-125 progression alone sufficient for entry/eligibility into clinical trials?

The purpose of this study was to evaluate the safety and efficacy of cetuximab (C225), an antibody that inhibits epidermal growth factor receptor (EGFR) activity, with cisplatin and to explore associations between EGFR protein expression with patient demographics or clinical outcome.Women with advanced, persistent, or recurrent carcinoma of the cervix were eligible. The women received cisplatin at 30mg/m(2) on days 1 and 8 with a loading dose of cetuximab at 400mg/m(2) followed by 250mg/m(2) on days 1, 8, and 15 in a 21day cycle. Adverse events were assessed with CTCAE v 3.0. Primary measure of efficacy was tumor response by RECIST. The study was stratified by prior chemotherapy (CT). EGFR protein expression in pre-treatment tumor was analyzed by immunohistochemistry.Between September 2004 and March 2008, 76 patients were enrolled. Of these, 69 were eligible and evaluable; 44 (64%) received prior chemotherapy. There were 4 responses in each group, prior chemotherapy and no chemotherapy, 9% and 16%, respectively. Grade 4 toxicities included anemia (1), allergy (1), metabolic (1), and vascular (1). The most common grade 3 toxicities were metabolic (15), dermatologic (8), fatigue (6), and gastrointestinal (6). EGFR protein was expressed in 47/48 (98%) of tumors analyzed with a median cellular expression of 81%. Exploratory analyses revealed a trend between the percentage of cells expressing EGFR protein and PFS (hazard ratio=1.76, 95% confidence interval=0.96-3.21).The combination of cetuximab with cisplatin was adequately tolerated but did not indicate additional benefit beyond cisplatin therapy.

BACKGROUND Among malignancies of the uterine cervix, the percentage of adenocarcinomas seems to have increased in recent reports. METHODS The clinical presentation of adenocarcinoma of the uterine cervix during the past 25 years was examined by review of charts and pathologic specimens. The data of a total of 124 patients with cervical adenocarcinoma treated between 1964 and 1988 were evaluated. RESULTS During the 25-year period, the percentage of adenocarcinoma among all cervical malignancies increased from 9% to 25%. In addition, the average number of new cases per year increased from 3.7 to 10.8. The percentage of women young than 35 years with adenocarcinoma increased from 16% in 1964 to 24% in 1989. Of these younger women, 74% had disease discovered by cytopathology, in comparison with 27% of the patients who were older than 35 years. The overall percentage of patients with disease diagnosed by cytology increased from 24% in the first half to 39% in the second half of the study period. Vaginal bleeding was the most common symptom. In the entire period, 57% of patients had International Federation of Gynecology and Obstetrics (FIGO) Stage I disease, with a median tumor diameter of 1 cm in patients with no symptoms and 3 cm in patients with symptoms. Outcome was inversely related to stage, tumor volume, and the presence of lymph node metastasis but not to histologic tumor type. CONCLUSION The frequency of adenocarcinoma of uterine cervix is increasing in patients 35 years or younger. Cytopathology is a good screening tool for these patients, leading to earlier diagnosis and improved outcome.

Preparation for pelvic exenteration is a traumatic experience for every patient, especially so when the procedure has to be aborted because of advanced disease. This occurred in 111 of 394 patients who underwent exploration for possible pelvic exenteration for recurrent cervical cancer at the University of Texas M. D. Anderson Cancer Center between 1970 and 1990. We reviewed these cases to better delineate preoperative factors predictive of unresectability. Distributions of initial stages and pathological diagnoses were similar to those for all cases of primary cervical cancer. The median time from primary therapy to recurrence was 12 months. The reasons for aborting the procedure included the presence of peritoneal disease in 49 patients (44%), for which the only preoperative finding with significant correlation was the presence of a pelvic mass (P = 0.03). Other reasons for aborting the procedure included nodal disease in 45 patients (40%), related to a short interval from primary therapy (P = 0.008) and the notation of fibrosis on preoperative exam (P = 0.01), parametrial fixation in 15 patients (13%), and hepatic lesions or bowel involvement in 5 patients (4.5%). Peritoneal cytology was negative in 61 of 79 patients (77.2%) and was of predictive value only in patients with adenocarcinoma. In conclusion, disseminated disease can seldom be detected during preoperative work-up. Evaluation of nodal status with computed tomography, lymphangiogram and directed fine-needle aspiration, and examination of peritoneal cytology in cases with adenocarcinoma, are the best available means of reducing the number of aborted procedures.

Purpose Platinum and taxane compounds have demonstrated activity in uterine carcinosarcoma (malignant mixed Mullerian tumor). Ifosfamide plus paclitaxel is the regimen with established superiority based on a randomized phase III trial conducted through the Gynecologic Oncology Group. However, the toxicity, multiday schedule, and limited activity of this regimen support further development of novel regimens. Our primary objective was to estimate the antitumor activity and toxicity of paclitaxel plus carboplatin in patients with uterine carcinosarcomas. Patients and Methods Eligible patients had advanced stage (III or IV), persistent or recurrent measurable disease, and no prior chemotherapy. Patients received paclitaxel at 175 mg/m2 intravenously (IV) over 3 hours plus carboplatin (area under the serum concentration-time curve = 6) IV over 30 minutes every 3 weeks until disease progression or until adverse effects occurred. Common Terminology Criteria for Adverse Events v3.0 was used to grade adverse events. Results Fifty-five patients were entered onto the study with nine being excluded from analysis, leaving 46 evaluable for analysis. Treatment was well tolerated with expected hematologic toxicity and minimal nonhematologic grade 4 toxicity (one cardiovascular and two pain) with 59% of patients completing six or more cycles of chemotherapy. The proportions of patients with confirmed complete and partial responses were 13% and 41%, respectively, resulting in a total overall response rate of 54% (95% CI, 37% to 67%). Conclusion Paclitaxel plus carboplatin demonstrates antitumor activity against uterine carcinosarcoma with acceptable toxicity and warrants further evaluation in phase III randomized trials.

Background Many quality of life instruments assess the amount of paid work in combination with role function at home in the same items and do not specifically assess social support in the workplace. The goal of this study was to obtain women's views on the relationship between employment and health-related quality of life. Methods A focus group and questionnaire study was conducted among 73 women with gynecologic cancer who were employed at diagnosis and 25 people who provided them with psychosocial support. Results The women held a variety of blue collar and white collar jobs at diagnosis. Employment provided a strong sense of accomplishment and a welcome distraction during treatment. The employment experience was described as distinct from role function at home. No one equated working more hours with better quality of life. Social support at work could be poor at the same time that support from family and friends grew stronger. Conclusions The contribution to their quality of life that cancer survivors feel they receive from employment may not be linearly related to the quantity of their role function in the workplace. Employment-related items could be useful as an adjunct to standard quality of life measures.

Our primary objective is to identify the issues that are of greatest concern to women in each of three treatment stages: newly diagnosed with ovarian cancer, in-treatment, and post-treatment. A longitudinal, repeated measures design will be used to assess changes in problem areas and quality of life from diagnosis to recurrence among women newly diagnosed with ovarian cancer. The CARES-SF and FACT-O questionnaires will be administered to participants following diagnosis and prior to chemotherapy, during chemotherapy, following chemotherapy, and after recurrence. Data collection for the study will last 28 months (patient accrual will last 25 months and follow-up will continue an additional 3 months). Data for the study will be collected through in-person interviews, and mailed questionnaires (with possible telephone follow-up) from women treated at the Wake Forest University Baptist Medical Center (WFUBMC) and Forsyth Medical Center (FMC).

Cervical cancer is one of the leading causes of cancer mortality in women worldwide, yet few suitable animal models currently exist for study of this disease. Virtually all cases of cervical cancer in women are caused by specific types of genital human papillomavirus (HPV). In this study, we investigated naturally occurring genital PVs in female cynomolgus macaques ( Macaca fascicularis ) without breeding contact for at least 3.5 years. Exfoliated cervicovaginal cells from 19 of 54 animals tested positive for at least one PV. Seven different PVs were identified, including four novel genotypes and two genotypes (RhPV-d and RhPV-a) previously identified in rhesus macaques ( Macaca mulatta ). Four PV types were associated with cervical intraepithelial neoplasia (CIN), which resembled human CIN by endoscopy, cervical cytology, histology, and immunohistochemistry. The presence of CIN was highly associated with PV infection ( P < 0.0001). The most prevalent virus type was RhPV-d, which was identified in 60% of animals with CIN. An RhPV-d genome sequenced from a high-grade CIN lesion was found to be phylogenetically related to the highly oncogenic HPV16. Transfer of cervical cytobrush samples from donor animals naturally carrying RhPV-d resulted in new infections in 4 of 12 previously virus-free animals and abnormal cytology and histology in 1 of 4 infected animals after 18 weeks of infection. Experimental transmission was confirmed by E1^E4 reverse transcription-PCR products and RhPV-d sequence identity with the donor variant. These findings identify key similarities between macaque and human oncogenic PVs which should prove useful in the study of viral persistence, carcinogenesis, and therapeutic development.

I nternational evidence-based consensus statements are important for defining standards of care and developing guidelines for communities worldwide. For ovarian cancer, successful international consensus meetings have been organized, and the most important was the meeting in Baden-Baden, Germany, in September 2004, which was organized by the Gynecological Cancer Intergroup. Its statements still are valid and are applied in daily routine. See related article on pages 692–702, this issue.

Objective Cyclic platinum-based intraperitoneal chemotherapy has proven to be effective after optimal surgical cytoreduction in ovarian carcinoma. Hyperthermia is directly cytotoxic and enhances chemotherapy tumoricidal effects. This study was designed to determine the maximum tolerated dose (MTD) of carboplatin used intraoperatively as intraperitoneal hyperthermic chemotherapy (IPHC), the effect on postoperative systemic chemotherapy administration, and the potential for repeat IPHC at second look surgery. Methods Using the ThermoChem™ HT System, escalating doses of carboplatin (400, 600, 800, 1000, and 1200 mg/m 2 ) were administered intraoperatively as IPHC with a perfusion time of 90 min. A subgroup of eight patients that received initial IPHC and subsequent systemic chemotherapy underwent second look reassessment surgery with IPHC. Results The first 4 dose levels were well tolerated without dose-defining toxicity. The initial two patients treated at 1200 mg/m 2 developed grade 4 myelosuppression thus defining the MTD at 1000 mg/m 2 . Newly diagnosed ovarian cancer patients receiving the initial IPHC at the MTD defined above completed standard systemic chemotherapy with six courses of systemic chemotherapy. Eight patients having initial IPHC and systemic chemotherapy subsequently had repeat IPHC performed at second look laparotomy without grade 3 or 4 toxicities. Four patients were found to have extensive adhesions at the time of second look reassessment surgery yet completed IPHC. Conclusions The MTD for intraperitoneal carboplatin administered as IPHC was established at 1000 mg/m 2 . IPHC at the initial cytoreductive procedure did not preclude subsequent systemic chemotherapy. In addition, repetitive IPHC was feasible at second look reassessment surgery.

The 3rd International Ovarian Cancer Consensus Conference (OCCC), held 3–5 September 2004, in Baden-Baden, Germany, addressed 12 questions critical to the future directions of clinical research into the treatment of newly diagnosed ovarian cancer. Four of these questions examined issues related to the current standard of care and to what should, for now, constitute a proper control arm in future phase III clinical trials. These questions are listed in Table 1. Consensus on the answer to these four questions is crucial to the interpretation of major clinical trials. Such a consensus will encourage the use of similar standards in each major trial and thus will provide a common basis for interpretation. This article will provide a detailed discussion of the rationale for the unanimous consensus achieved for each of these four questions.

2004 consensus statements on the management of ovarian cancer : final document of the 3rd International Gynecologic Cancer Intergroup Ovarian Cancer Consensus Conference (GCIG OCCC 2004).

The aim of this study was to identify the psychosocial needs of patients after treatment for gynecological malignancies and their views concerning the role physicians should take in meeting those needs. Self-administered questionnaires were answered by 95 patients at least 6 months after completion of therapy. Topic areas included emotional needs, spiritual concerns, patient-family communication, patient participation in decision making, and advance directives. In addition, all participants completed the Functional Assessment of Cancer Therapy (FACT-G, version 4) quality of life questionnaire. Fifty-seven percent of respondents stated that they had needed help dealing with emotional problems, and 73% wanted the physician to ask whether help is needed. The most common emotional concerns were feeling nervous (40% of subjects), being worried (34%), fear (25%), needing someone to talk to (24%), sadness (21%), and loss of control (17%). Fifty-nine percent stated that physicians should ask whether help is needed in discussing spiritual matters. Sixty-one percent stated that physicians should ask patients whether they want help starting conversations with their families about difficult-to-raise topics such as the possibility of dying. Forty-six of 86 respondents (53%) stated that discussions about advance directives such as living wills should take place soon after the cancer diagnosis has been established. Most patients surveyed want physicians to take an active role in dealing with psychosocial needs.

Objective. The aim of the study was to investigate the use of the cavitron ultrasonic surgical aspirator (CUSA) for the treatment of vulvar intraepithelial neoplasia (VIN) as it combines the advantage of laser removal of the superficial dermal layers without scars and the advantage of resection with collection of a pathological specimen. Methods. Between 1992 and 1998, 37 patients with VIN were treated using the CUSA. Charts were reviewed retrospectively. Results. The median age at diagnosis was 40 years. Eleven patients (30%) had been previously treated for VIN. Diagnosis was made by inspection before and after ascitic acid application, colposcopy, and multiple biopsies revealing VIN II in 8 patients (22%) and VIN III in 29 patients (78%). At least two quadrants of the vulva were involved in 16 cases (43%) and three or four quadrants in 12 cases (33%). Under anesthesia the CUSA was used to remove all lesions with a 1-cm margin. There were no complications except 1 admission for pain control. Healing was complete in 4 to 6 weeks and no patient developed scarring. Final pathology confirmed the preoperative diagnostic grade in 24 cases (65%), while upgrading to a higher dysplasia occurred in 4 patients (11%). A second treatment was necessary in 3 patients with widespread disease. Patients were followed for an average of 33 months. Thirteen recurrences (35%) developed after a median interval of 16 months. Recurrences were significantly ( P = 0.004) more frequent if VIN involved hair-bearing tissue, 6 of 7 (86%) cases, in contrast to patients with disease confined to the labia minora and introitus, 7 of 30 (23%) cases. Conclusion. CUSA is an acceptable treatment alternative for VIN confined to non-hair-bearing vulvar skin.