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Circulating tumor cells (CTCs) are viable tumor cells that are released into the circulatory system. CTCs have shown a prognostic value in numerous solid tumors. CTC research in epithelial ovarian carcinoma (EOC) has attracted only little attention. Since the primary route of metastasis in EOC is considered to be direct peritoneal spread in the abdominal cavity and distant metastases only occur in one third of the patients, it was thought that there is not enough shedding of tumor cells in the circulation. Nevertheless recent studies revealed an important role of hematogenous spread in EOC and showed that CTC status is associated with advanced tumor stage, CA-125 levels and residual disease after surgery. Furthermore the presence of CTCs correlates with shorter overall and disease free survival. However this prognostic value of CTCs in EOC seems to depend on the used isolation and detection methods. In EOC function- or density based enrichment methods seem to offer more promising results then epithelial cell adhesion molecule (EpCAM)-based approaches. This can be explained by a low number of EpCAM positive CTCs in EOC and the downregulation of EpCAM during epithelial-to-mesenchymal transition (EMT). The presence of CTCs might also have predictive value as CTC status was associated with treatment response in two studies and CTCs showed to be a better monitoring tool then CA-125 in a small population. The (genotypic) characterization of CTCs might become even more important in the future paving the way for CTCs to a true predictive “liquid tumor biopsy”. [ABSTRACT FROM AUTHOR]

Abstract: Aim: Due to its high sensitivity, magnetic resonance (MR) mammography is increasingly used as adjunct to mammography and ultrasound. The technique, however, has a relatively limited specificity. Therefore, it may only be used for specific indications. One of the indications is preoperative staging of breast carcinoma. This review serves to give an overview of the studies published on the role of MR in preoperative local staging. Methods: We reviewed studies of the role of MR mammography in the detection of breast carcinomas and in the assessment of the diameter and extent of carcinomas. We also reviewed published studies on detection of multifocal and multicentric carcinomas that were occult on mammography and ultrasound. Advantages and drawbacks of preoperative MR mammography and the effect on treatment, as reported in different published studies, are described. The review is based on a search of PubMed, using specific terms for the different topics. Results: MR has the highest sensitivity to detect invasive carcinomas and is best in assessment of tumor extent, including detection of multifocal, multicentric and bilateral disease. Conclusion: MR mammography is a valuable adjunct to conventional imaging in the preoperative local staging of breast cancer. [Copyright &y& Elsevier]

Objective: We sought to investigate whether angiogenesis can predict the risk of recurrence of cervical intraepithelial neoplasia after treatment.Study Design: Microvessel density was studied in 75 patients with grade 3 cervical intraepithelial neoplasia and in 20 patients with microinvasive squamous carcinoma (International Federation of Gynecology and Obstetrics stage IA1) of the uterine cervix by staining representative tissue sections with the specific endothelial marker anti-CD31. The microvessel density was determined with a digital image analyzer. The results were correlated with clinical and histopathologic data.Results: The mean vessel density was 264 per field (range, 86-674 per field) in grade 3 cervical intraepithelial neoplasia and 378 per field (range, 161-848 per field; P = .001) in microinvasive squamous carcinoma. Thirteen patients with grade 3 cervical intraepithelial neoplasia had recurrent cervical intraepithelial neoplasia (microvessel density, recurrent vs nonrecurrent; not significant). Multiple regression analysis in the noninvasive group confirmed that the mean vessel density (P = .121) had no prognostic value. Furthermore, it showed that the age at diagnosis (P = .011), menopausal status (P = .052), and treatment modality (P = .022) proved to be independent prognostic factors for recurrence.Conclusions: During the progression from noninvasive to microinvasive cervical carcinoma, the microvessel density increases significantly. However, the vessel density does not predict recurrence of noninvasive lesions. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to determine risk factors for trocar implantation metastasis after diagnostic laparoscopy in patients with primary or recurrent advanced ovarian cancer.Study Design: Eighty-three women with primary advanced ovarian cancer and 21 women with recurrent ovarian cancer undergoing a laparoscopy for a tissue diagnosis and for assessment of operability were included in the study. The occurrence of implantation metastasis at the trocar incision scars was analyzed according to clinicopathologic characteristics.Results: A recurrence developed at the trocar site in 7 (58%) of 12 patients undergoing a laparoscopy in which only the skin was closed at the end of the procedure and in 2 (2%) of 92 patients undergoing a laparoscopy with closure of all layers (odds ratio, 63; 95% confidence interval, 10.3-385; P <.001). The International Federation of Gynecology and Obstetrics stage at initial presentation, tumor histologic type, tumor differentiation, maximal tumor diameter at the time of diagnosis, estimated weight of the metastatic tumor, residual tumor after cytoreductive surgery, surgical characteristics, and type of chemotherapy were well balanced among both groups. Patients with implantation metastasis had significantly more ascites (median, 700 mL vs 300 mL; P =.032) and a longer interval between the start of platinum-based chemotherapy or cytoreductive surgery (median, 6 days vs 17 days; P <.01) compared with patients without abdominal wall recurrence. A palpable abdominal wall metastasis developed in none of the patients undergoing a laparoscopy with closure of all layers of the abdomen followed by cytoreductive surgery or chemotherapy within 1 week after the laparoscopy. Kaplan-Meier survival analysis showed that patients with abdominal wall implantation metastasis had a survival rate similar to that of the other patients.Conclusions: Laparoscopy with careful closure of the peritoneum, rectus sheath, and skin followed by chemotherapy or cytoreductive surgery with excision of the trocar trajectories within 1 week is safe in patients with disseminated ovarian cancer. [ABSTRACT FROM AUTHOR]

Objective: The oncoprotein bcl-2 inhibits apoptosis. The purpose of this study was to assess the expression of bcl-2 in human cervical carcinoma and to correlate this with clinicopathologic parameters.Study Design: Immunohistochemical staining for bcl-2 protein (MoAB clone 124) was performed on operative tissue specimens from 22 patients with carcinoma in situ of the cervix and from 137 patients with invasive cervical carcinoma (International Federation of Gynecology and Obstetrics stages I to IV). The immunoreactivity of bcl-2 was scored as positive (> or = 5% staining cells) or negative (< 5% staining cells).Results: Eighty-two percent of in situ carcinomas and 61% of invasive cervical carcinomas were bcl-2 positive. Expression of bcl-2 was correlated to tumor stage (p < 0.001) and to presence of vascular (p < 0.005) or lymphatic tumor (p < 0.023) permeation. In univariate analysis there was a strong relationship between bcl-2 expression and overall survival (p < 0.001). In multivariate analysis bcl-2 expression (p < 0.001), International Federation of Gynecology and Obstetrics stage (p = 0.011), and presence of lymphatic permeation (p = 0.014) proved to be independent prognostic factors.Conclusions: Expression of bcl-2 is lost during tumor progression and is a strong prognostic parameter, suggesting that the regulation of apoptosis plays an important role in the behavior of cervical carcinomas. Better understanding of the mechanisms involved may lead to improved medical treatment strategies. [ABSTRACT FROM AUTHOR]

Objective: Our purpose was to evaluate the effectiveness, benefits, and potential side effects of the use of the cavitational ultrasonic surgical aspirator for cytoreduction of advanced ovarian cancer.Study Design: Forty patients with stage IIC to IV ovarian carcinoma were randomized to undergo ultraradical cytoreductive surgery with (group 1, 20 patients) or without (group 2, 20 patients) the use of the CUSA 200 cavitational ultrasonic surgical aspirator (Valleylab, Boulder, Colo). Preoperative and postoperative information and follow-up data were collected prospectively and compared between both groups.Results: The amount of residual tumor after debulking surgery, the duration of the operation, and the rate of perioperative complications were comparable in both study groups. The amount of perioperative blood loss was significantly lower (1450 ml vs 1650 ml, p=0.02) in group 1. These patients had less morbidity (p<0.05), and could be discharged from the hospital significantly sooner (14 days vs 16 days, p=0.031). CA 125 levels 1 and 2 months after surgery were significantly lower in the group with cavitational ultrasonic surgical aspirator (p<0.01 and p<0.01, respectively), suggesting more successful cytoreduction. However, this is not reflected in a better disease-free or overall survival.Conclusion: Cavitational ultrasonic surgical aspirator-assisted cytoreductive surgery of advanced ovarian carcinoma is more effective in eradicating disease, reduces morbidity, and is cost beneficial. [ABSTRACT FROM AUTHOR]

Cervical cancer can and should be a historical disease. The reality, however, is that every year more than half a million women are diagnosed with cervical cancer and a quarter of a million die of this disease. The causal factor for cervical cancer is a persistent HPV infection and therefore a vaccine was developed: prophylactic HPV vaccination will reduce cervical cancer by 70%. Screening based on cytology will miss more than 40% of the abnormalities. The introduction of vaccination should lead to the reintroduction of cervical cancer screening based on HPV detection. Primary HPV screening followed by cytology will detect almost all abnormalities. Not all HPV tests, however, are the same! Clinicians are generally not aware that there is a huge difference among HPV tests. If a low grade lesion progresses to a high grade or invasive cancer, their HPV is likely to integrate. During integration L1 expression can be lost, but E6/E7 expression will always remain present. If the viral HPV is completely integrated then a L1 test looking for only L1 expression will miss this (pre)cancer, while the E6/E7 test will not miss it. HPV tests used in cervical cancer screening should be based on the early (E) and the late (L) genes in order not to miss the abnormality. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: Levonorgestrel (LNG), delivered locally into the uterine cavity has a profound effect on the endometrium. The aim of the study was to use a LNG intrauterine system to treat non-atypical and atypical endometrial hyperplasia in women and to evaluate the long-term cure (remission) rate. Methods: Each of the 20 women in the study, of whom eight were diagnosed with atypical hyperplasia, received a LNG–IUS, releasing 20μgLNG/day. The study is a non-comparative study with long-term follow-up (range 14–90 months). Results: All women developed a normal endometrium, except one asymptomatic woman with atypical hyperplasia who still had focal residual non-atypical hyperplasia at 3 years follow-up in the presence of a thin (<4mm) endometrium. Conclusion: Continuous intrauterine delivery of LNG appears to be a promising alternative to hysterectomy for the treatment of endometrial hyperplasia and could enhance the success rate when compared with other routes of progestagen administration as well as intrauterine progesterone delivery. The significant reduction of the PR expression observed during treatment with the LNG–IUS appears to be a marker for the strong antiproliferative effect of the hormone at a cellular level resulting in an inhibition of estrogen bioactivity and endometrial suppression. [Copyright &y& Elsevier]

Objective: To investigate endometrial histology and thickness of the endometrium after long-term use of continuous transdermal estrogen substitution combined with intrauterine release of levonorgestrel (LNG) in postmenopausal women. Design: A 5-year non-comparative prospective clinical trial. Subjects: Out of 182 symptomatic postmenopausal women using estrogen substitution therapy (EST) combined with a novel T-shaped LNG-releasing intrauterine system (Femilis Slim LNG-IUS), to prevent endometrial proliferation and bleeding, only those women (n=102) who used two consecutive LNG-IUSs, were isolated with the aim to study the long-term effects on the endometrium. The mean age of the women was 57 years (range 47-71). The majority of women received percutaneous 17beta estradiol, 1.5mg daily, or an equivalent dose by patch or orally, on a continuous basis. Main Outcome Measures: Endometrial histology and ultrasonographic evidence of endometrial suppression, after a period of approximately 5 years of use. The mean duration of use of the regimen was 70 months (range 25-98). Results: The dominant endometrial histologic picture was that of inactive endometrium characterized by glandular atrophy and stroma decidualization (Kurman classification 5b). No cases of endometrial hyperplasia were found. On transvaginal ultrasound, this corresponds with a thin endometrium (< or = 5 mm). Conclusion: The results of this 5-year study in 102 postmenopausal women using EST demonstrates that the LNG-IUS effectively opposes the estrogenic effect on the endometrium resulting in strong suppression during the entire period of EST. Due to its high efficacy and absence of systemic effects on organ tissues (e.g., breasts), target delivery in the uterine cavity could be a preferred route to administer a progestagen in women using EST. [ABSTRACT FROM AUTHOR]

PURPOSE: The study was designed to determine independent prognostic variables in suboptimally debulked advanced ovarian cancer patients entered in the randomised phase III study EORTC 55865. EXPERIMENTAL DESIGN: Retrospectively collected paraffin blocks from 169 patients with stages IIb-IV epithelial ovarian cancer, taken at primary debulking surgery, were analysed. All patients were treated with cyclophosphamide and cisplatin (CP), and followed up for a median of 10 years. Expression of p53, bcl-2, P21, Ki-67 and HER-2 status was assessed by immunohistochemistry (IHC). RESULTS: Expression of p21, a downstream effector of the p53 gene, was found to be a favourable prognostic factor for survival (HR 0.58, CI 0.36-0.94, p=0.025) in addition to FIGO stage (HR 1.54, CI 1.08-2.21, p=or<0.02). For progression free survival (PFS), both p21 (HR 0.52) and Ki-67 (HR 0.6) were significant factors. CONCLUSION: P21 overexpression is a positive prognostic factor for survival and PFS in advanced ovarian carcinoma with residual lesions of more than 1 cm. [ABSTRACT FROM AUTHOR]