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Background: Breast magnetic resonance imaging (MRI) with conventional screening methods improves sensitivity in high-risk patients without benefits on specific survival. We evaluated the characteristics, treatments, and prognostic features of breast cancers diagnosed among BRCA1/2 mutation carriers either inside or outside screening programs that included MRI., Patients and Methods: Two groups of patients diagnosed with a new breast cancer between 2001 and 2007 were compared: group 1, patients included in an intensive screening program; and group 2, patients outside of this program., Results: Twenty-one patients met inclusion criteria for group 1, and 102 for group 2. Seventy-four percent and 65%, respectively, were BRCA1 mutation carriers. Tumors in both groups had the same characteristics (pN, grade, estrogen receptor, progesterone receptor, HER2 expression), except for smaller tumor size in group 1 (median, 6 mm vs. 22 mm; P < .0001). Group 1 patients had more frequent sentinel node procedures (57% vs. 28%; P = .021) and less commonly received chemotherapy (43% vs. 86%; P < .0001). The 3-year disease-free survival (93% vs. 74%; P = .1) and the 3-year overall survival (100% vs. 92%; P = .2) did not differ between groups., Conclusion: MRI might provide improvement in BRCA1/2 carriers in terms of smaller tumor size and treatment morbidity. However, because of aggressive intrinsic characteristics, this does not turn into significant survival benefits.

The impact of chemotherapy on a woman's fertility depends on her age and the types and doses of the drugs used. Alkylating agents have the biggest negative impact on ovarian function. A trial is currently examining the use of a GnRH agonist to protect ovarian function. The impact of external radiation therapy and brachytherapy on the ovaries depends on three factors: the patient's age, the dose delivered to the ovaries, and concurrent use of chemotherapy. Ovarian transposition is a simple surgical procedure that can be used in selected cases to reduce the risk of early menopause. Both external and internal radiation has an impact on the uterus, notably by altering its vascularization and by reducing its growth when treatment is delivered during childhood.

Background: The histological results of pelvic lymphadenectomy were studied in patients treated for early-stage cervical cancer (<4 cm) who had no nodal uptake on [(18)F]fluorodeoxyglucose positron-emission tomography combined with integrated computed tomography (FDG-PET/CT)., Patients and Methods: Patients treated between 2005 and 2008 for stage IB1 cervical cancer cancer <4 cm who underwent a FDG-PET/CT followed by surgical evaluation of pelvic nodes were reviewed., Results: A total of 16 patients were studied. The median age of patients was 43 (range 29-62) years. Surgery was performed laparoscopically and by laparotomic approach in 13 and 3 cases, respectively. Two patients had histologically proven pelvic involvement. The false-negative rate and negative predictive value of PET-CT imaging for pelvic nodal involvement were 13% and 87%, respectively., Conclusion: The accuracy of PET-CT imaging in predicting the pelvic nodal status is very low in patients with early-stage cervical cancer and is not able to replace lymphadenectomy.

Breast cancer (BC) is the most frequently occurring cancer in women; early diagnosis and efficient treatments create higher event-free and overall survival rates. However, the mean age at first pregnancy continues to increase worldwide; the question of pregnancy after BC is thus raised more frequently. Chemotherapy may induce premature ovarian failure, depending largely on the woman's age and the drugs used, as well as the dosage and duration of treatment. It is important that fertility preservation strategies are addressed before chemotherapy. Pregnancy after BC may implicate a potentially higher risk of cancer recurrence, but the available literature provides reassuring data. The delay between cancer treatment and pregnancy should be discussed, depending on the initial stage of the disease. The risk of discontinuing tamoxifen prematurely should be carefully evaluated using standardised tools. The pregnancy outcome may as well be impaired by the history of cancer, leading to an increased likelihood of preterm birth and low birth weight rates. Proper follow-up and prevention should be provided based on the knowledge of these complications. Pregnancy after BC should be possible for most young BC patients in the future. This implies a global care program including multi-disciplinary teams is initiated prior to starting adjuvant treatment and particularly chemotherapy. The patient and her partner should be involved in the various steps of the process, after being properly informed., (Copyright 2009 Elsevier Ltd. All rights reserved.)

Background: The aim of this study was to assess the outcomes of the largest series of patients treated conservatively for a stage II or III serous borderline ovarian tumor., Materials and Methods: From 1969 to 2006, 41 patients were treated conservatively for an advanced-stage serous borderline ovarian tumor. Patient outcomes were reviewed., Results: Twenty patients had undergone a unilateral salpingo-oophorectomy, 18 a unilateral cystectomy and two bilateral cystectomy (unknown for one patient). Three patients had invasive implants. The median duration of follow-up was 57 months (range 4-235). The recurrence rate was high (56%), but overall survival remained excellent (100% at 5 years, 92% at 10 years). One death had occurred due to an invasive ovarian recurrence. Eighteen pregnancies (nine spontaneous) were observed in 14 patients., Conclusions: This study demonstrates that spontaneous pregnancies can be achieved after conservative treatment of advanced-stage borderline ovarian tumors (with noninvasive implants) but the recurrence rate is high. Nevertheless, this high rate has no impact on survival. Conservative surgery can be proposed to patients with a borderline tumor of the ovary and noninvasive peritoneal implants. Should infertility persist following treatment of the borderline tumor, an in vitro fertilization procedure can be cautiously proposed.

Purpose: The aim of this study was to evaluate the prognostic factors and morbidities of patients undergoing completion surgery for locally advanced-stage cervical cancer after initial chemoradiation therapy (CRT)., Patients and Methods: Patients fulfilling the following inclusion criteria were studied: stage IB2-IVA cervical carcinoma, tumor initially confined to the pelvic cavity on conventional imaging, pelvic external radiation therapy with delivery of 45 Gy to the pelvic cavity and concomitant chemotherapy (cisplatin, 40 mg/m(2) per week) followed by uterovaginal brachytherapy, and completion surgery after the end of radiation therapy including at least a hysterectomy., Results: One-hundred fifty patients treated in 1998-2007 fulfilled the inclusion criteria. Prognostic factors for overall survival in the multivariate analysis were the presence and level of nodal spread (positive pelvic nodes alone: hazard ratio [HR], 2.03; positive para-aortic nodes: HR, 5.46; p < .001) and the presence and size of residual disease (RD) in the cervix (p = .02). Thirty-seven (25%) patients had 55 postoperative complications. The risk for complications was higher with a radical hysterectomy (p = .04) and the presence of cervical RD (p = .01)., Conclusion: In this series, the presence and size of RD and histologic nodal involvement were the strongest prognostic factors. Such results suggest that the survival of patients treated using CRT for locally advanced cervical cancer could potentially be enhanced by improving the rate of complete response in the irradiated area (cervix or pelvic nodes) and by initially detecting patients with para-aortic spread so that treatment could be adapted in such patients. The morbidity of completion surgery is high in this context.

Background: Accurate localisation of the lumpectomy cavity (LC) volume is one of the most critical points in 3D-conformal Partial breast irradiation (3D-APBI) treatment planning because the irradiated volume is restricted to a small breast volume. Here, we studied the role of the placement of surgical clips at the 4 cardinal points of the lumpectomy cavity in target delineation., Methods: Forty CT-based 3D-APBI plans were retrieved on which a total of 4 radiation oncologists, two trainee and two experienced physicians, outlined the lumpectomy cavity. The inter-observer variability of LC contouring was assessed when the CTV was defined as the delineation that encompassed both surgical clips and remodelled breast tissue., Results: The conformity index of tumour bed delineation was significantly improved by the placement of surgical clips within the LC (median at 0.65). Furthermore, a better conformity index of LC was observed according to the experience of the physicians (median CI = 0.55 for trainee physicians vs 0.65 for experienced physicians)., Conclusions: The placement of surgical clips improved the accuracy of lumpectomy cavity delineation in 3D-APBI. However, a learning curve is needed to improve the conformity index of the lumpectomy cavity.

The treatment of the advanced ovarian adenocarcinoma, most frequently stage at diagnostic, relies on association of surgery and chemotherapy. The current standard is the association carboplatine-paclitaxel. In spite of this treatment, relapses are frequent, and the prognosis thus remains very reserved. Presently the current areas of research aim at both improving the efficiency of treatments and decreasing their toxicity. So the various trials dealt with the use of the other cytotoxics having proved efficiency against relapses either in double-agent therapy or in association in the current standard, or in the administration of the chemotherapy by intra peritoneal way. They also investigated the possibility of pursuing the therapeutic sequence by a treatment of maintenance or consolidation. As for numerous cancerous pathologies, the targeted therapies, notably the antiangiogenic one, represent an important hope in the treatment of the ovarian cancer.

Upper abdomen cytoreduction is an important and challenging surgery that should be considered only if a macroscopically complete cytoreduction is expected. Techniques of the main procedures are addressed herein, as well as their respective morbidity and indications. Given its complexity, this surgery should be reserved to specialized teams, working in specialized centers.

Objective: The aim of this study was to evaluate the prognostic impact of the histological response at the time of interval debulking surgery (IDS) in patients treated with neoadjuvant chemotherapy (NACT) for unresectable advanced-stage ovarian cancer (ASOC)., Study Design: A retrospective study to select cases fulfilling 4 inclusion criteria: (1) patients with unresectable ASOC; (2) at least 3 courses of platinum and paclitaxel NACT; (3) patients who underwent IDS after NACT and who were free of macroscopic residual disease at the end of debulking surgery and (4) histologic analysis of specimens performed in the same institution. Patients were classified into 3 groups according to the histological response to NACT group 1: no histologic residual disease; group 2: persistent residual disease but with marked histological changes and group 3: persistence of at least 1 site with no changes in the tumour. Survival was compared., Results: Fifty-eight patients (49 stage IIIC and 9 stage IV) fulfilled inclusion criteria. Respectively 8, 14 and 36 patients were in groups 1, 2 and 3. The median duration of follow-up was 41 months. Three-year event-free survival in groups 1, 2 and 3 was respectively: 63%, 12% and 19% (p=.02)., Conclusions: These results suggest that the degree of the histological response has a limited impact on survival when complete debulking surgery is achieved at IDS. The degree of tumour cell viability after initial chemotherapy is not a reliable marker for modifying chemotherapy after debulking surgery in such patients.

Background: The aim of this study was to assess the outcomes of patients treated for peritoneal or ovarian psammocarcinoma (PSC)., Materials and Methods: Review of patients with PSC who underwent cytoreductive surgery in our institution with a follow-up of more than 18 months (the ovarian or peritoneal tumor was histologically reviewed by our reference pathologist)., Results: From 1997 to 2006, 15 patients with PSC were histologically reviewed in our institution. Five of these patients fulfilled the inclusion criteria. Four patients had ovarian PSC, and 1 had peritoneal PSC. Four patients were surgically treated during initial management and another patient at the time of recurrence. All of them underwent complete cytoreductive surgery followed by intraperitoneal chemotherapy in 2 patients and by conventional adjuvant chemotherapy in 1. After a median follow-up of 42 months, 4 of them remain disease-free., Conclusions: Peritoneal or ovarian PSC is a rare low-grade carcinoma characterized by a more favorable prognosis than classic carcinoma. The place of debulking surgery at the time of initial or recurrent management is important.

Background: The objective of this study was to determine prognostic factors in a large series of patients with stage II or III serous low malignant potential ovarian tumor (LMPOT) and peritoneal implants., Methods: Patients with a serous LMPOT and peritoneal implants treated at or referred to our institution were retrospectively reviewed. The slides of ovarian tumors and peritoneal implants were reviewed by the same pathologist., Results: From 1969 to 2006, 168 patients were reviewed, 21 of whom had invasive implants. Tumors exhibited a micropapillary pattern in 56 patients. Adjuvant treatment had been administered to 61 patients. The median duration of follow-up was 57 months (range, 1-437). Forty-four patients had relapsed and 10 patients had died. The 5-year overall survival rate was 98%. Among patients with noninvasive and invasive implants, 8% and 10%, respectively, had relapsed at 5 years in the form of invasive disease (p = .08). In a multivariate analysis, the use of conservative treatment was the only prognostic factor., Interpretation: The prognosis of serous LMPOT with peritoneal implants remains good. The strongest prognostic factor in patients with an advanced-stage borderline tumor is the use of conservative surgery. In this series, a micropapillary pattern and implant subtype (invasive versus noninvasive) were not prognostic factors.

Early stage of cervical cancer is defined by disease confined to the cervix and upper vagina (stage IA to IIA). For early stage, no treatment has demonstrated clear superiority. Treatment options for women with early stage include either exclusive radiotherapy, or radical surgery, or brachytherapy before radical surgery. Radical hysterectomy or trachelectomy include the resection of the parametrium. The rational of parametrectomy is to remove occult disease in the parametrium and its removal is the cause of much of the morbidity of the surgery, specially urinary complications. This surgery can be performed by laparascopy with quality of life improvement and less blood loss but urinary morbidity is still important. The question is if it's possible to be less radical and still oncologically safe. Parametrial invasion is rare in patients with small tumours without lymphovascular space involvement and negative pelvic nodes (no poor prognostic factors). Sentinel node negative could be a strong criteria to predict parametrial involvement. This review reports studies exploring the safety of omitting parametrectomy in these low risk patients and the future possibilities to evaluate these new indications.

A role for the EGF system, in particular HER1 and 2, in growth of the endometrium has been suggested but HER1 and 2 have not been studied in all locations of endometriosis and in ovarian endometrioid adenocarcinoma (OEC) which is a rare form of malignant transformation of endometriosis. Immunohistochemistry (IHC) was used for studying HER1 and HER2 in ovarian (n = 10), peritoneal (n = 10), colorectal endometriosis (n = 20) and OEC (n = 10). Fluorescent in situ hybridisation (FISH) was used for analysing the status of HER2 gene in colorectal endometriosis and OEC. All samples were negative for HER2 in both glandular and stromal cells and in glandular cells for HER1 by IHC. In 15 out of 20 colorectal endometriosis, there was a weak expression in stromal cells. Following FISH, two colorectal samples had a partial 17 aneusomy and three OEC, a 17 polysomy. The other samples were 17 disomic without HER2 amplification; HER1 and 2 do not seem to have a role in endometriosis physiopathology.

The aim of this study was to assess the outcomes of women treated conservatively for a serous borderline ovarian tumour with stromal microinvasion (SBOT-SMI) but without micropapillary pattern. Ten women treated conservatively for a stage I (n= 8) or stage IIIB (n= 2) tumour were followed up. With a median follow-up duration of 62 months (range 7-117 months), five recurrences developed on the preserved ovary. All lesions were borderline recurrences (with noninvasive peritoneal implants in one). All women are currently disease free. Three women achieved a spontaneous pregnancy and three became pregnant after an in vitro fertilisation procedure. This study suggests that conservative treatment of SBOT-SMI is safe.

Background: Borderline ovarian tumours (BOT) do not exhibit overt stromal invasion and are less aggressive than invasive epithelial ovarian tumours. BOT also arise in younger patients than those who develop epithelial ovarian tumours. Our aim was to evaluate the feasibility of ovarian cryopreservation (OC) in patients treated for BOT., Methods: A retrospective study of data concerning young patients (less than 35 years of age) who underwent surgery for a BOT with OC planned during the surgical procedure., Results: Twenty-three patients, treated between January 2002 and February 2008, were initially selected but six of them were excluded from the present study (four because the tumour was malignant and two because it was benign). Finally, 17 patients were diagnosed as having BOT based on the frozen section analysis. In nine (53%) of these cases, OC was finally performed. In eight cases, OC was not performed; instead, in four cases a simple cystectomy was finally performed (one patient was in fact pregnant at the time of surgery), in one case malignant disease was found and in three (18%) patients OC was not technically feasible because no normal ovarian parenchyma was evident on gross inspection., Conclusion: In patients treated for a BOT, OC was eventually feasible in 53% of patients in whom this procedure was initially planned. In 18%, this procedure was aborted because no macroscopic healthy ovarian tissue could be found.

Background: Gene-expression arrays have generated molecular predictors of relapse and drug sensitivity in breast cancer. We aimed to identify exons differently expressed in malignant and benign breast lesions and to generate a molecular classifier for breast-cancer diagnosis., Methods: 165 breast samples were obtained by fine-needle aspiration. Complementary DNA was hybridised on splice array. A nearest centroid prediction rule was developed to classify lesions as malignant or benign on a training set, and its performance was assessed on an independent validation set. A two-way ANOVA model identified probe sets with differential expression in malignant and benign lesions while adjusting for scan dates., Findings: 120 breast cancers and 45 benign lesions were included in the study. A molecular classifier for breast-cancer diagnosis with 1228 probe sets was generated from the training set (n=94). This signature accurately classified all samples (100% accuracy, 95% CI 96-100%). In the validation set (n=71), the molecular predictor accurately classified 68 of 71 tumours (96%, 88-99%). When the 165 samples were taken into account, 37 858 exon probe sets (5.4%) and 3733 genes (7.0%) were differently expressed in malignant and benign lesions (threshold: adjusted p<0.05). Genes involved in spliceosome assembly were significantly overexpressed in malignant disease (permutation p=0.002). In the same population of 165 samples, 956 exon probe sets presented both higher intensity and higher splice index in breast cancer than in benign lesions, although located on unchanged genes., Interpretation: Many exons are differently expressed by breast cancer and benign lesions, and alternative transcripts contribute to the molecular characteristics of breast malignancy. Development of molecular classifiers for breast-cancer diagnosis with fine-needle aspiration should be possible.

Background: With the widespread development of genomic analysis, an accurate and quick method for obtaining high-quality nucleic acids is needed. The objective of the current study was to evaluate the quality and potential use of material obtained from fine-needle aspiration cytology (FNAC)., Methods: Ultrasound- or palpation-guided FNAC was performed in 124 consecutive patients who had nodular breast lesions. The authors evaluated the amount of messenger RNA (mRNA) obtained, its quality through the RNA Integrity (RIN) score, and the factors that influenced both. For malignant lesions, the authors attempted to correlate estrogen receptor 1 (ESR1) and HER-2 (c-erb-B2) mRNA expression measured by real-time quantitative polymerase chain reaction with estrogen receptor and HER-2 detection obtained by immunohistochemistry (IHC) and/or fluorescent in situ hybridization (FISH) on the surgical specimen., Results: The amount of mRNA obtained was >1 microg in 89.5% of 124 samples (43 benign lesions and 81 adenocarcinomas). Overall, 59.3% of samples yielded >1 microg RNA with a RIN score >6. The most significant predictors of quality and quantity of mRNA were the cytopathologist who sampled the tumors and a diagnosis of cancer versus benign lesion. The median ESR1 expression level, which was expressed as the polymerase chain reaction cycle threshold (CT) level minus the average 18S value (dct), was 17.7 dct in patients with estrogen receptor-negative tumors and 11.1 dct in patients with estrogen receptor-positive tumors. The median HER-2 expression level was 15.1 dct in patients with HER-2-negative tumors and 10.7 dct in patients with HER-2-positive tumors. mRNA expression was concordant with the IHC/FISH evaluation in 90.3% of patients for estrogen receptor status and in 98.5% of patients for HER-2 status., Conclusions: In 70% of cases, FNAC of breast lesions in well trained hands allowed the extraction of mRNA suitable for gene expression analysis., ((c) 2009 American Cancer Society.)

S. Gouy, C. Uzan, Y. Zafrani, C. Lhommé, P. Pautier, P. Duvillard, C. Haie-Meder, P. Morice Uterine cancer can metastasize to both the pelvic and para-aortic levels. No one questions the diagnostic and prognostic value of lymphadenectomy, but its therapeutic value is still open to debate. In early cervical cancer (<4 cm.), pelvic lymphadenectomy is a routine part of radical hysterectomy. If pelvic lymph nodes show involvement, one can propose an extension of the lymphadenectomy to the para-aortic level. Studies of sentinel lymph node identification and biopsy at this level are currently under way. The standard treatment of cervical cancer > 4 cm is radiotherapy. A pre-radiation laparoscopy to investigate lymph node involvement at the lumbo-aortic level may help to define the extent of the radiation field. For endometrial cancer, the role and benefit of lymphadenectomy are much less clear since these patients often have major co-morbidities which increase the risk of complications from an extended lymph node dissection., (Copyright © 2008 Elsevier Masson SAS. All rights reserved.)

S. Gouy, C. Uzan, Y. Zafrani, C. Lhommé, P. Pautier, P. Duvillard, C. Haie-Meder, P. Morice Uterine cancer can metastasize to both the pelvic and para-aortic levels. No one questions the diagnostic and prognostic value of lymphadenectomy, but its therapeutic value is still open to debate. In early cervical cancer (<4 cm.), pelvic lymphadenectomy is a routine part of radical hysterectomy. If pelvic lymph nodes show involvement, one can propose an extension of the lymphadenectomy to the para-aortic level. Studies of sentinel lymph node identification and biopsy at this level are currently under way. The standard treatment of cervical cancer > 4 cm is radiotherapy. A pre-radiation laparoscopy to investigate lymph node involvement at the lumbo-aortic level may help to define the extent of the radiation field. For endometrial cancer, the role and benefit of lymphadenectomy are much less clear since these patients often have major co-morbidities which increase the risk of complications from an extended lymph node dissection., (Copyright © 2008 Elsevier Masson SAS. All rights reserved.)

Objective: The aim of this study was to assess the outcomes of patients treated conservatively for a serous borderline ovarian tumor with micropapillary patterns (SBOT-MP)., Methods: Retrospective study collecting cases of conservative treatment of SBOT-MP. There are 15 patients treated with conservative management for a stage I (n = 8) or III (n = 7) SBOT-MP. Eight patients underwent a unilateral salpingo-oophorectomy with a contralateral cystectomy, three a unilateral salpingo-oophorectomy, two a cystectomy, and two a bilateral cystectomy. Four patients had stromal microinvasion associated with MP at histological examination of the ovarian tumor. Noninvasive implants were observed in eight patients and invasive implants in one. Three patients had residual disease <1 cm on the peritoneum. One patient received adjuvant chemotherapy., Results: After a median interval of 63 months (range, 18-120 months), 11 recurrences were observed: six of them exclusively on the ovary, three exclusively on the peritoneum (invasive peritoneal disease in one), and two on the ovary and peritoneum. One of the last two patients succumbed to the recurrence (under the form of invasive adenocarcinoma). The other patients were actually disease free. Five patients achieved eight spontaneous pregnancies., Conclusion: This study demonstrates that spontaneous pregnancies can be achieved after conservative treatment of SBOT-MP. Nevertheless, as 2/3 of patients had bilateral ovarian involvement at the time of initial management, the recurrence rate is high. However, making definitive conclusions about the safety of conservative surgery is limited by the small sample size. So, further studies are warranted to evaluate conservative management of advanced-stage disease.

Uterine cancer can metastasize to both the pelvic and para-aortic levels. No one questions the diagnostic and prognostic value of lymphadenectomy, but its therapeutic value is still open to debate. In early cervical cancer (<4 cm.), pelvic lymphadenectomy is a routine part of radical hysterectomy. If pelvic lymph nodes show involvement, one can propose an extension of the lymphadenectomy to the para-aortic level. Studies of sentinel lymph node identification and biopsy at this level are currently under way. The standard treatment of cervical cancer>4 cm is radiotherapy. A pre-radiation laparoscopy to investigate lymph node involvement at the lumbo-aortic level may help to define the extent of the radiation field. For endometrial cancer, the role and benefit of lymphadenectomy are much less clear since these patients often have major co-morbidities which increase the risk of complications from an extended lymph node dissection.

Background: The evaluation of residual disease (RD) after chemoradiation therapy (CRT) in stage IB2/II cervical carcinoma conventionally is based on a clinical examination and magnetic resonance imaging (MRI) performed 3 to 8 weeks after the end of treatment. Very few studies have correlated MRI and histologic findings specifically in cervix cancer. This was the objective of the current study., Methods: A retrospective review was undertaken of patients who fulfilled the following inclusion criteria: 1) stage IB2/II cervical cancer, 2) external radiotherapy (45 grays [Gy]) was given with concomitant chemotherapy followed by uterovaginal brachytherapy (15 Gy), 3) MRI studies were obtained between 3 weeks and 8 weeks after brachytherapy, and 4) completion surgery included at least a hysterectomy. Postsurgical histologic findings and MRI results were compared., Results: Forty-four patients who were treated between 2003 and 2006 fulfilled all inclusion criteria. Twelve patients (27%) had achieved a radiologic complete response, 16 patients (36.5%) had unclassified lesions (RD or 'fibrosis'), and 16 patients (36.5%) had radiologic residual tumor. According to the histologic results, 19 patients (43%) had no RD, 10 patients (23%) had inframillimeter RD, 2 patients (5%) had RD that measured <1 cm, and 13 patients (29%) had RD that measured >1 cm. The sensitivity and specificity of MRI in evaluating RD were 80% and 55%, respectively., Conclusions: The current results indicated that the evaluation of RD 3 to 8 weeks after CRT with MRI is difficult, and the risk of false-positive results is high. Another radiologic procedure or a more technologically advanced MRI technique, such as diffusion-weighted MRI, should be evaluated., ((c) 2008 American Cancer Society.)

Background: The prognosis for patients who develop a recurrence after fertility-sparing surgery for epithelial ovarian cancer (EOC) remains unclear. This is the first study to evaluate survival in patients who have developed a recurrence in this context., Methods: The outcomes of relapsed patients reported in the literature in the four main series of fertility-sparing surgery for EOC were reviewed and updated (where feasible)., Results: Twenty-three of the 166 patients in the series were reported to have recurrent disease. The site of the recurrence was the peritoneum (+/- remaining ovary) in 17 patients, and distant in six patients. Twelve patients died of recurrent disease, two are still alive with persistent disease, eight are disease-free, and one is alive but her exact status is not known. Among eight patients (34%) with an isolated recurrence on the remaining ovary, two died and one was lost to follow-up., Conclusion: In this carefully monitored population, including systematic radiological examinations, the rate of isolated recurrences on the spared ovary is low. Recurrence in these patients carries a poor prognosis. Such results suggest that initial selection of candidates for fertility-sparing surgery should be carefully defined to reduce the rate of recurrences that carry a poor prognosis.

Background: The aim of this study was to determine the influence of the different histological subtypes (serous versus non-serous) on the location of nodal metastases in patients undergoing pelvic and para-aortic lymphadenectomies during the initial management of epithelial ovarian tumors., Methods: We carried out a retrospective analysis of data concerning patients fulfilling the following inclusion criteria: (1) an epithelial ovarian tumor; (2) a complete pelvic and bilateral para-aortic lymphadenectomy up to the level of the left renal vein; (3) surgical procedures including lymphadenectomies performed before adjuvant chemotherapy; and (4) a description of the distribution of positive nodes removed between pelvic and para-aortic areas. Patients were classified into two groups according to the histological subtypes: serous (group 1) and non-serous (group 2) tumors., Results: Of patients treated between 1989 and 2005, 148 fulfilled the inclusion criteria: 73 had a serous tumor and 75 a non-serous tumor. Positive nodes were observed in 70 (47%) patients-47 (64%) in group 1 and 23 (31%) in group 2 (P < 0.05). But the distribution of involved nodes between pelvic and para-aortic areas in patients with positive nodes was not statistically different between the two groups. In both groups, the most common site for positive nodes in the para-aortic area was the left para-aortic group: 74% in group 1 and 61% in group 2 (NS)., Conclusions: This series suggests that the histological subtype has no impact on the distribution of positive nodes in pelvic and para-aortic areas in patients with epithelial ovarian tumors.

Introduction: Ovarian cancer is the leading cause of death from gynaecological malignancy, especially because of late diagnosis. The objective of the study was to provide the clinician with current concepts regarding prevention of ovarian cancer., Material and Methods: A computerized search of articles published was performed using the Medline database We performed a review of the literature (PubMed, Embase) using the following search terms (MeSH and non-MeSH): prevention, chemoprevention, chemoprevention, ovarian cancer, ovarian, ovary, carcinoma, tumor, tumour., Results: Oral contraceptive and acetaminophen use may provide substantial protection against ovarian cancer, whereas aspirin, carotenoids and non-steroidal anti-inflammatory agents do not decrease the risk. However, to date, there is no recommendation concerning low risk population. At the opposite, young women (<35-40 years old) presenting with BRCA1 or 2 mutation or Lynch syndrome may be counseled for chemoprevention using oral contraceptive. For high risk women over 35-40 years old, prophylactic bilateral salpingo-oophorectomy should be performed. Indeed, it has been showed that prophylactic surgery significantly decrease mortality rates in high risk women., Conclusion: Large randomized studies are required to assess the efficacy of ovarian cancer chemoprevention in low risk women. High-risk women over 35-40 years old should be counseled for prophylactic salpingo-oophorectomy or for chemoprevention using oral contraceptive.

Background: Pelvic radiation therapy with concomitant chemotherapy (PCRT) is the standard treatment of stage IB2/II cervical carcinoma. The impact of concomitant chemotherapy on positive para-aortic nodes (PA+), however, remains unknown. The aim of this study was twofold: to evaluate the rate of histological PA+ after PCRT and to determine the survival of patients with PA+., Methods: Patients fulfilling the following inclusion criteria were studied: (1) stage IB2/II cervical carcinoma, (2) histological subtype: squamous cell, adenocarcinoma or an adenosquamous tumor, (3) exclusion of patients with radiological PA+ (CT scan/MRI), (4) pelvic external radiation therapy of 45 Gy with concomitant chemotherapy (cisplatin 40 mg/m2/week) + utero-vaginal brachytherapy, and (5) completion surgery after the end of PCRT including at least a para-aortic lymphadenectomy., Results: Seventy-three patients (16 stage IB2, 57 stage II) treated between 1998 and 2004 fulfilled all the inclusion criteria. PA+ after PCRT were observed in 13 patients (18%) with a median of five (range, 2-22) positive nodes. Overall and disease-free survival at 24 months in patients with PA+ was 40% and 17%. Only two patients with PA+ are currently alive and in remission., Conclusions: The rate of PA+ remains high after PCRT in patients treated for stage IB2/II cervical carcinoma. Furthermore, the survival rate of patients with PA+ is very low. These important results suggest that detection of PA + at the time of completion surgery (after PCRT) is not beneficial for improving survival.

When a former breast cancer patient asks for pregnancy, several questions have to be considered. The physician has to answer and counsel clearly and honestly his/her patient regarding the possibilities, risks and specificities associated with a pregnancy in this case. The individual risk of relapse should be considered, together with individual predictive factors and theoretical benefits of specific prolonged treatments such as hormone therapy. Both risks associated with the pregnancy itself and with the modification of treatment schemes have to be evaluated. Risks related to Assisted reproductive techniques when indicated, should also be considered and explained. Potential foetal risks should be explained too. The aim of this review is to summarize the current knowledge and then available tools that the physician can use to help the couple making decision regarding subsequent pregnancy.

Objective: The aim of this study was to review the results of completion surgery after chemoradiation therapy in stage IB2/II cervical carcinoma., Methods: Analysis of series published in the literature about completion surgery in this context., Results: Stages of the disease included in those series were stage IB2-IVA disease. The rate of residual disease was correlated with initial stage of the disease and the use of preoperative brachytherapy. Morbidity of such management varied between 15% and 47% and was correlated with the radicality of the surgical procedure and the size of the residual disease. The rate of complete pathological response varied between 52% and 76%. The survival of patients was correlated with the presence and the size of the residual disease and the presence of a nodal involvement., Conclusion: Completion surgery after chemoradiation therapy has a place in the multimodality management of stage IB2 or II cervical cancer, particularly in cases of bulky residual disease. Nevertheless further investigations are needed, particularly with collaborative studies, to analyze the real impact of such surgery on the survival of patients.

Human papillomavirus (HPV) are responsible of an important morbidity and mortality. HPV is a significant source of morbidity and mortality. HPV is the most common sexually transmitted infection: adolescents are at high-risk for HPV acquisition. Biologic and epidemiologic studies have demonstrated that HPV infection is a necessary but non-sufficient cause of cervical cancer and genital warts. The vast majority of cervical cancers contain high-risk HPV type and approximately 70% contain HPV types 16 or 18. HPV types 6 or 11 are responsible for approximately 90% of genital warts. Thus, a vaccine that could prevent. Prophylactic vaccines based on the use of virus-like particles (VLPs) obtained by auto-assembly of L1 are under clinical trials. Two vaccines are currently evaluated: Cervarix (GlaxoSmithKline Biologics), a bivalent vaccine against HPV 16 and 18, and Gardasil (Merck & Co) a quadrivalent vaccine against HPV 16, 18, 6, and 11. Phase I, II and III studies have demonstrated that both vaccines are well tolerated and provide an excellent immunogenicity. With approximately 5-year follow-up, both vaccines have been effective in preventing persistent infection with targeted HPV types and in preventing cervical intraepithelial lesions. The optimal target for vaccination is probably 12-year-old girls.

Matrix metalloproteinase (MMPs) expression has been linked to gynecological tumor aggressiveness. The objective of this study was to determine MMP-2, MMP-7, and MMP-9 and tissue inhibitors of metalloproteinases (TIMP)-1 and TIMP-2 expression in endometrial malignancies and their relation to clinical and histologic parameters. Formalin-fixed, paraffin-embedded tumor samples from 50 patients with endometrial carcinoma treated between 1999 and 2004 were stained with specific monoclonal antibodies. The tumors were grouped according to the FIGO classification. The staining results were compared to histologic and clinical data. Semiquantitative analysis of MMP and TIMP expression showed a significant difference in TIMP-2 expression according to the histologic subtype (P = 0.03) and also a trend towards a difference in MMP-9 expression (P = 0.05). MMP-2 expression increased and TIMP-2 expression fell as the histologic grade increased (P = 0.0007, P < 0.0001, respectively). MMP-2 expression correlated with lymph node metastasis (P = 0.04), while TIMP-2 expression correlated with the depth of myometrial invasion (P = 0.01), vasculolymphatic space involvement (P = 0.02), and lymph node metastasis (P = 0.0003). These results support the involvement of MMPs and TIMPs in endometrial tumor growth and progression. High MMP-2 and low TIMP-2 expression were the most potent markers of endometrial tumors with a high risk of local and distant spread.

Endometriosis is defined as the presence of endometrial glands and stroma outside the uterus. Apoptosis, a physiological process by which multicellular organisms eliminate superfluous cells, is altered in tumor tissue. Here we studied the expression of the apoptosis-related proteins p53, bcl-2, bax, p21 and fas in proliferative (n=9) and secretory (n=9) endometrium, and in peritoneal (n=11), ovarian (n=20) and colorectal (n=20) endometriosis, by qualitative and semi-quantitative immunohistochemical methods using the percentage of positive cells and HSCORE analysis. In endometrium, p53, p21 and fas expression was low, whereas bax and bcl-2 expression was elevated. Using HSCORE analysis, only bcl-2 expression varied during the menstrual cycle (48.9+/-34.2% in the proliferative phase, 11.5+/-24.7% in the secretory phase, p=0.01). Using HSCORE analysis, p53 expression was higher in ovarian endometriosis than in peritoneal (p<0.0001) and colorectal endometriosis (p=0.03). P21 expression was higher in ovarian endometriosis than in peritoneal (p=0.01) and colorectal endometriosis (p=0.01). Bcl-2 expression was lower in ovarian endometriosis than in peritoneal (p=0.0002) and colorectal endometriosis (p<0.0001). Fas expression was higher in peritoneal endometriosis than in ovarian (p=0.02) and colorectal endometriosis (p=0.008). In conclusion, these results confirm the involvement of apoptosis in the pathogenesis of endometriosis. Moreover, expression of apoptosis-related proteins varies according to the location of endometriosis suggesting the involvement of different apoptotic pathways.

Objectives: To determine the feasibility and short and midterm results of laparoscopic pelvic exenteration for cervical cancer relapse. Materials and methods. Five patients with centro-pelvic recurrence within 3 to 13 months after combined chemo-radiation therapy (associated to surgery for two cases) for cervical cancer tumors were included in a pilot study., Results: The procedures consisted in a complete pelvic exenteration with colo-anal anastomosis and ileal-loop conduit for 2 patients, a posterior pelvic exenteration including uterus, vagina and rectum with colo-anal anastomosis for 1 patient, an anterior pelvic exenteration including bladder and vagina with an ileal-loop conduit for 1 patient and a anterior pelvic exenteration with a laparoscopic hand assisted Miami Pouch for 1 patient. The 5 procedures were successful with no conversion to laparotomy. Time of procedure ranged between 4 h 30 and 9 hours. Average blood loss was 370 cc. Three patients developed metastatic recurrences and died. The two patients with anterior exenteration are alive and free of disease 11 and 15 months after the procedure., Conclusion: Laparoscopic pelvic exenteration procedures are feasible. A larger series is necessary to determine the advantages of this technique compared to laparotomy.

Background: We examined the expression of apoptosis-related proteins in serous versus mucinous borderline ovarian tumours, in comparison with benign and malignant ovarian tumours., Materials and Methods: Immunohistochemical expression of pro-apoptotic (p53, p21, bax, bak, fas) and anti-apoptotic proteins (bcl-2, bcl-x) was determined in 34 borderline (19 mucinous, 15 serous), 20 benign (10 mucinous, 10 serous) and 28 malignant ovarian tumours (9 mucinous, 19 serous)., Results: A difference in semi-quantitative p53 expression was found between benign and borderline tumours (P = 0.01), but not between borderline and malignant tumours. Increased p21 expression was found in borderline versus benign tumours (P = 0.004). Bcl-2 expression was lower in borderline than in benign (P = 0.01) and malignant tumours (P = 0.02). No difference in bax, bak, fas or bcl-x expression was observed among the three tumour types. Higher percentage of p21 positive cells was found in serous than in mucinous borderline tumours (P < 0.001). Bcl-2 expression was higher in serous than in mucinous forms of benign (P < 0.001), borderline (P < 0.001), and malignant tumours (P < 0.003). No difference in p53, bax, bak, fas or bcl-x expression was observed between serous and mucinous borderline ovarian tumours., Conclusion: Although p53 overexpression was a common feature of both mucinous and serous borderline tumours, p21 and bcl-2 overexpression appeared specific to serous tumours., (2005 Wiley-Liss, Inc.)

Background: Endometriosis is defined by the presence of endometrium outside the uterus. Changes in the expression of the proto-oncogene c-kit are associated with aggressive behaviour of both benign and malignant tumours, but there are few data on its c-kit expression in endometriosis. Here we examined c-kit expression in endometrium and endometriotic tissue., Methods: Immunohistochemistry was used for qualitative and semi-quantitative (mean+/-S.D. positive cells) analysis of c-kit expression in endometrium from women with (n=9) and without endometriosis (n=18), and in peritoneal (n=20), ovarian (n=20) and colorectal endometriosis (n=20)., Results: Semi-quantitative c-kit expression was higher in endometrial glandular cells from women with endometriosis than from women without endometriosis (15.0+/-14.6% versus 3.9+/-7.4%, p=0.01). No difference in c-kit expression was found in qualitative analysis and according to the phase of the menstrual cycle. C-kit expression values in peritoneal, ovarian and colorectal endometriosis were 2.0+/-3.8%, 2.0+/-4.1% and 21.7+/-18.4%, respectively. Qualitative and semi-quantitative c-kit expression was higher in colorectal endometriosis than in peritoneal and ovarian endometriosis (p<0.001); no difference was found between ovarian and peritoneal endometriosis. No c-kit expression was detected in stromal cells of either endometrium or endometriotic tissue., Conclusion: These results suggest that the c-kit/stem cell factor axis is involved in the pathogenesis of endometriosis. Strong c-kit protein expression was associated with invasive endometriotic lesions.

Endometriosis is subsequent to the ability of endometrial glands to invade normal tissues. Matrix metalloproteinases (MMPs)--enzymes that mediate normal tissue turnover, including endometrial breakdown during menstruation-appear to be involved in this invasive process. Here, we examined the immunohistochemical expression of MMP-2, MMP-3, MMP-11, tissue inhibitor metalloproteinase (TIMP)-1 and TIMP-2 in endometrium from women with (n=9) or without endometriosis (n=18) in comparison with peritoneal (n=20), ovarian (n=20) and colorectal endometriosis (n=20). Women with endometriosis showed decreased endometrial MMP-2 expression compared with women without endometriosis (mean+/-SD positive cells: 24.3+/-28.3% and 69.3+/-12.1%), together with loss of MMP-3 expression (0 versus 17.5%+/-20.2). MMP-11, TIMP-1 and TIMP-2 expression was similar in the two groups. Endometrial MMP-2, -3 and -11 expression and TIMP-1 and -2 expression were similar in women with endometriosis and in those with peritoneal endometriosis. MMP-2, -3 and -11 expression was higher in colorectal endometriosis than in ovarian and peritoneal endometriosis. TIMP-2 expression was lower in colorectal endometriosis (P=0.0002) and ovarian endometriotic cysts (P=0.003) than in peritoneal endometriosis. TIMP-1 expression did not vary according to the location of endometriotic lesions. These results suggest that MMP-2 and -3 and TIMP-2 may be involved in the pathogenesis of endometriosis. Interestingly, MMP-2 and -3 overexpression was related to the infiltrative nature of endometriotic lesions, with possible sequential expression from peritoneal to colorectal endometriosis.

Background: The aim was to study the prognosis for and survival of patients treated with combined therapy (including surgical resection) for nodal recurrences from epithelial ovarian cancer (EOC)., Methods: This was a retrospective study of a group of 12 patients with a recurrence from EOC, a priori, exclusively located in lymph node(s). All patients underwent surgical resection of nodal metastases, followed by adjuvant therapy., Results: The median age of patients was 51 (range, 42-71) years. The initial disease stages were as follows: stage IA, n = 5; stage IIA, n = 1; and stage IIIC, n = 6. The median interval between the end of initial treatment and the nodal relapse was 21 (range, 6-72) months. The recurrence was located in the abdominal nodes in 10 patients (pelvic and/or para-aortic area) and was extra-pelvic in one patient, and the last patient had concomitant para-aortic and supraclavicular nodal involvement. Ten patients received postoperative chemotherapy and two had radiation therapy (one patient received both treatments). Eight patients relapsed and four did not. To date, three patients have died of the disease, three are alive with persistent disease, and six are alive and disease-free (including two patients who were treated by surgical resection after relapses twice in abdominal nodes). Five-year overall survival from the time of treatment of recurrent disease is 71% (confidence interval, 41%-90%)., Conclusions: The prognosis of patients with an a priori isolated nodal recurrence from EOC was good in this group of treated with surgical resection followed by chemoradiation or radiation therapy. This finding argues in favor of proposing surgical resection in such patients.