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1.
Radiology ; 273(1): 117-24, 2014 Oct.
Article in English | MEDLINE | ID: mdl-24828001

ABSTRACT

PURPOSE: To prospectively determine the accuracy of 3.0-T magnetic resonance (MR) enterography in the preoperative assessment of deep infiltrating endometriosis (DIE) lesions located in the bowel above the rectosigmoid junction. MATERIALS AND METHODS: Institutional review board approval for this study was obtained, and each patient gave written informed consent. Over 18 months, patients with known pelvic DIE who were scheduled for surgery were recruited. Consecutive patients suspected of having bowel endometriosis above the rectosigmoid junction underwent 3.0-T MR enterography. Two blinded readers independently performed a systematic analysis of nine bowel segments above the rectosigmoid junction. MR images were compared with surgical and pathologic findings. Efficacy parameters were calculated with 95% confidence intervals (CIs). Interobserver agreement was assessed with κ statistics. RESULTS: Among the 43 patients enrolled in this study, 33 underwent surgery and were included in the final analyses. Sixteen (48%) patients had bowel DIE lesions located above the rectosigmoid junction at surgery and histopathologic examination. Twenty-six lesions were analyzed, including four ileal, two ileocecal, three cecal, three appendicular, and 14 sigmoid colon lesions. For the diagnosis of these lesions, MR imaging showed sensitivities of 92% (95% confidence interval [CI]: 81.7, 100) for reader 1 and 96% (95% CI: 87.1, 100) for reader 2 and specificities of 100% (95% CI: 98.8, 100) for both readers. The κ value was 0.97. CONCLUSION: These results show 3.0-T MR enterography is accurate in the preoperative diagnosis and mapping of bowel DIE lesions located above the rectosigmoid junction. Online supplemental material is available for this article.


Subject(s)
Endometriosis/diagnosis , Intestinal Diseases/diagnosis , Adult , Contrast Media , Endometriosis/surgery , Female , Humans , Intestinal Diseases/surgery , Magnetic Resonance Imaging/methods , Meglumine/analogs & derivatives , Middle Aged , Organometallic Compounds , Prospective Studies
2.
Gynecol Oncol ; 128(3): 568-72, 2013 Mar.
Article in English | MEDLINE | ID: mdl-23159816

ABSTRACT

OBJECTIVE: To describe the clinical and histological pitfalls in the diagnosis of placental site trophoblastic tumours (PSTT) and epithelioid trophoblastic tumours (ETT), two rare types of gestational trophoblastic neoplasia (GTN). METHODS: This retrospective, observational, study was carried out in the French Trophoblastic Disease Reference Centre, Lyon, between 2000 and 2011. Due to the many similarities in the diagnosis, treatment and prognosis of PSTT and ETT, these two types of tumour were investigated together. Twenty-two patients with PSTT or ETT were analysed. RESULTS: The clinical presentation of these two types of tumour was irregular vaginal bleeding (55%) or amenorrhoea (27%), with a median plasma hCG level of 205IU/L. Seven of the 22 patients (32%) were initially misdiagnosed as an ectopic pregnancy. Median age at presentation was 35-years, with a median interval of 12months between the antecedent pregnancy and diagnosis of PSTT or ETT. The initial histological diagnosis was incorrect in 7/18 (39%) patients; there was a major disagreement with the referral pathologist in five of these seven patients (28%). CONCLUSIONS: PSTT and ETT are the most difficult types of GTN to diagnose clinically and histologically. An incorrect diagnosis can lead to significant therapeutic deviations from the recommended first-line treatment, namely hysterectomy. Clinical and histological expertise is essential to avoid the pitfalls in the diagnosis of PSTT and ETT.


Subject(s)
Gestational Trophoblastic Disease/diagnosis , Placenta/pathology , Trophoblastic Tumor, Placental Site/diagnosis , Adult , Female , Gestational Trophoblastic Disease/pathology , Gestational Trophoblastic Disease/surgery , Humans , Hysterectomy , Middle Aged , Placenta/surgery , Pregnancy , Retrospective Studies , Trophoblastic Tumor, Placental Site/pathology , Trophoblastic Tumor, Placental Site/surgery , Young Adult
3.
Fertil Steril ; 97(3): 691-6, 2012 Mar.
Article in English | MEDLINE | ID: mdl-22245530

ABSTRACT

OBJECTIVE: To investigate the functional and sexual outcome of sigmoid vaginoplasty in patients with Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome. DESIGN: Prospective study. SETTING: University hospital. PATIENT(S): Fifty-nine consecutive patients with MRKH syndrome. INTERVENTION(S): Forty-eight patients underwent sigmoid vaginoplasty, and 11 were treated using the Frank method of dilatation. MAIN OUTCOME MEASURE(S): Functional results and sexuality were evaluated with the use of two standardized questionnaires: the Female Sexual Function Index (FSFI) and the revised Female Sexual Distress Scale (FSDS-R). Questions were added to analyze depression, body image perception, and desire of motherhood. RESULT(S): Out of the 68% of patients who answered the questionnaire, 73% had regular sexual intercourse. The mean total FSFI score was 28 ± 3.1 in the operated group and 30 ± 5.3 in the group treated with the Frank method. Their mean FSDS-R scores were 21 ± 12.1 and 18 ± 13.8, respectively. CONCLUSION(S): Sigmoid vaginoplasty is an effective technique providing a nearly normal sexual function to patients with vaginal aplasia. Despite this, psychologic distress related to sexuality persists in most patients, demonstrating the need for a multidisciplinary support.


Subject(s)
46, XX Disorders of Sex Development/surgery , Abnormalities, Multiple/surgery , Gynecologic Surgical Procedures , Sexuality , Surgically-Created Structures , Vagina/surgery , 46, XX Disorders of Sex Development/physiopathology , 46, XX Disorders of Sex Development/psychology , Abnormalities, Multiple/physiopathology , Abnormalities, Multiple/psychology , Adoption/psychology , Body Image , Chi-Square Distribution , Congenital Abnormalities , Depression/etiology , Female , France , Gynecologic Surgical Procedures/adverse effects , Hospitals, University , Humans , Insemination, Artificial, Heterologous/psychology , Kidney/abnormalities , Mullerian Ducts/abnormalities , Patient Satisfaction , Perception , Recovery of Function , Somites/abnormalities , Spine/abnormalities , Surgically-Created Structures/adverse effects , Surrogate Mothers/psychology , Surveys and Questionnaires , Treatment Outcome , Uterus/abnormalities , Uterus/physiopathology , Uterus/surgery , Vagina/abnormalities , Vagina/physiopathology , Young Adult
4.
Hum Reprod ; 26(10): 2651-7, 2011 Oct.
Article in English | MEDLINE | ID: mdl-21840909

ABSTRACT

OBJECTIVE: To evaluate the contribution of referent pathologists (RPs) to the quality of diagnosis of trophoblastic diseases and to study the level of diagnostic agreement between the initial pathologists and the RPs. METHODS: This observational retrospective study was carried between 1 November 1999 and 11 January 2011 using the database of the French Trophoblastic Disease Reference Centre in Lyon. All files for hydatiform moles (HMs), trophoblastic tumours and non-molar pregnancies for which there was an initial suspicion of trophoblastic disease were included, whenever there was rereading of the slides by an RP. A total of 1851 HMs and 150 gestational trophoblastic tumours were analysed. RESULTS: When the initial pathologist diagnosed a complete mole, the RP confirmed the diagnosis in 96% of cases. When the initial pathologist diagnosed a partial mole, the RP confirmed the diagnosis in only 64% of cases. For trophoblastic tumours, when the initial pathologist diagnosed a choriocarcinoma, the RP confirmed the diagnosis in 86% of cases. When the initial anatomopathology suggested an invasive mole, the diagnosis was confirmed in 96% of cases. Finally, when the initial diagnosis was a placental site trophoblastic tumour or an epithelioid trophoblastic tumour, the RP confirmed the diagnosis in 60 and 100% of cases, respectively. CONCLUSION: A systematic policy of rereading of slides for all suspicious moles improves the quality of management of trophoblastic diseases at a national level.


Subject(s)
Gestational Trophoblastic Disease/diagnosis , Hydatidiform Mole/diagnosis , Pathology/methods , Trophoblastic Neoplasms/diagnosis , Adolescent , Adult , Choriocarcinoma/diagnosis , Diagnosis, Differential , Female , Humans , Hydatidiform Mole, Invasive/diagnosis , Middle Aged , Observer Variation , Pregnancy , Pregnancy Complications/diagnosis , Referral and Consultation , Reproducibility of Results , Retrospective Studies
5.
Eur J Obstet Gynecol Reprod Biol ; 158(2): 334-7, 2011 Oct.
Article in English | MEDLINE | ID: mdl-21669485

ABSTRACT

OBJECTIVE: To evaluate three predictive risk models of non-sentinel lymph node (NSLN) involvement in the case of micrometastatic sentinel node (SLN) involvement for breast cancer. STUDY DESIGN: This retrospective study included 72 successive patients with micrometastatic SLN involvement who had surgery between March 1996 and October 2007. All patients had undergone immediate or delayed axillary lymph node dissection (ALND). The Memorial Sloan-Kettering Cancer Center (MSKCC) nomogram, the Stanford nomogram and the Tenon score were applied to the population to calculate the probability of NSLN involvement. RESULTS: For the MSKCC nomogram with a threshold value of 10%, sensitivity was 50%, specificity was 70% and the negative predictive value (NPV) was 89%. The area under the receiver operating characteristic curve (AUC) was 0.6 (significant). Use of this nomogram would have avoided ALND in 49 out of 72 (68%) patients, but five out of 10 (50%) patients with NSLN involvement would not have been detected. With a threshold value of 7%, the AUC was 0.69, sensitivity was 90% and NPV was 97%. ALND would have been avoided in 31 out of 72 (43%) patients, with a 3% chance of leaving metastases when abstaining from ALND. For the Tenon score with a threshold value of 3.5, sensitivity was 50%, specificity was 72% and the AUC was 0.62. This was not clinically applicable because eight out of 10 (80%) patients with NSLN involvement would not have been detected. For the Stanford nomogram, the results could not be interpreted because the AUC was not significant. CONCLUSION: None of the tested models are sufficiently reliable for use in daily practice. The MSKCC nomogram showed the most encouraging results, especially for a threshold value of 7%, but this has not been validated in the literature. Complete axillary dissection should be performed in the case of micrometastatic SLN involvement until more data become available.


Subject(s)
Breast Neoplasms/pathology , Carcinoma, Ductal, Breast/pathology , Carcinoma, Lobular/pathology , Lymph Node Excision , Lymph Nodes/pathology , Sentinel Lymph Node Biopsy , Adult , Aged , Axilla , Female , Humans , Lymphatic Metastasis , Middle Aged , Models, Statistical , Nomograms , Retrospective Studies , Risk Assessment
6.
Int J Gynecol Cancer ; 20(5): 809-14, 2010 Jul.
Article in English | MEDLINE | ID: mdl-20973274

ABSTRACT

Our objective was to determine if cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is a feasible therapeutic option for treatment of peritoneal recurrence of endometrial carcinoma. Between August 2002 and May 2007, 5 patients with recurrent endometrial carcinoma confined to the peritoneal cavity who underwent CRS with HIPEC. Cisplatin (1 mg/kg) and mitomycin C (0.7 mg/kg) were perfused at an inflow temperature of 46 to 48-C for 90 minutes under systemic hypothermia (32 °C). Of the 5 patients treated, histopathological type and International Federation of Gynecology and Obstetrics stage were as follows: IB endometrioid (n = 1), IIIA endometrioid (n = 1), IIIC endometrioid (n = 2), and IC endometrioid + pseudosarcomatoid component (n = 1). The mean interval from initial surgery to CRS with HIPEC was 47.5 months (10-120 months). In all patients, CRS was complete. One patient with pseudosarcomatoid component developed recurrent disease 10 months after surgery and died 2 months later. One patient experienced early recurrence with a malignant pleural effusion and died. Three patients are alive and disease free at 7, 23, and 39 months from surgery with good performance status. Regarding the toxicity of the procedure, highly selected patients with recurrent endometrial carcinoma confined to the peritoneal cavity may benefit from improved survival after CRS with HIPEC.


Subject(s)
Adenocarcinoma/therapy , Antineoplastic Agents/administration & dosage , Endometrial Neoplasms/therapy , Neoplasm Recurrence, Local/therapy , Peritoneal Neoplasms/therapy , Adenocarcinoma/secondary , Aged , Cisplatin/administration & dosage , Combined Modality Therapy , Endometrial Neoplasms/pathology , Female , Gynecologic Surgical Procedures , Humans , Hyperthermia, Induced , Infusions, Parenteral , Middle Aged , Mitomycin/administration & dosage , Peritoneal Neoplasms/secondary
7.
Am J Obstet Gynecol ; 200(6): 643.e1-6, 2009 Jun.
Article in English | MEDLINE | ID: mdl-19393597

ABSTRACT

OBJECTIVE: We sought to review efficacy and toxicity of an 8-day methotrexate (MTX) regimen in the treatment of patients with low-risk gestational trophoblastic neoplasia (GTN) from the French Trophoblastic Disease Reference Center. STUDY DESIGN: Between 1999 and 2006, 142 low-risk GTNs were diagnosed according to International Federation of Gynecology and Obstetrics (FIGO) criteria for GTN and to the FIGO scoring system. We report their characteristics, remission/resistance/recurrence rates, and treatment toxicity. RESULTS: The 8-day MTX regimen achieved a 77.5% remission rate. All patients but 1 (99.9%) achieved remission and remained disease free until the time of analysis. Severe (grade 3 or 4) blood/bone marrow toxicity and metabolic/laboratory toxicity was noted in 4.2% of cases, of which 2 (1.4%) were grade 4. CONCLUSION: For patients with GTN diagnosed according to FIGO criteria and considered low risk according to the FIGO scoring system, an 8-day MTX regimen is an adequate treatment associating a high rate of remission to a low rate of toxicity.


Subject(s)
Antimetabolites, Antineoplastic/therapeutic use , Gestational Trophoblastic Disease/drug therapy , Methotrexate/therapeutic use , Adolescent , Adult , Antimetabolites, Antineoplastic/toxicity , Female , Gestational Trophoblastic Disease/classification , Humans , Methotrexate/toxicity , Middle Aged , Pregnancy , Risk Factors , Young Adult
8.
Eur J Obstet Gynecol Reprod Biol ; 143(2): 84-7, 2009 Apr.
Article in English | MEDLINE | ID: mdl-19193484

ABSTRACT

OBJECTIVE: Twin pregnancy with complete hydatidiform mole and coexistent fetus (CHM&CF) is a rare situation and a challenge for diagnosis. Results related to fetal outcome and maternal risk of subsequent gestational trophoblastic neoplasia (GTN) are controversial. We here display a series from the French Trophoblastic Disease Reference Center, which is to date the third in number of cases registered by the same center. STUDY DESIGN: By retrospective method based on patients from the French Trophoblastic Disease Reference Center data base between November 1999 and December 2006, 17 assumed cases were reviewed. In 14 cases the diagnosis of CHM&CF was ascertained. All files were reviewed to confirm diagnosis. Methods of initial diagnosis, outcome of pregnancy and evolution to GTN were studied. RESULTS: In 10 cases (71%) diagnosis was made by ultrasonography. Differential diagnoses were partial hydatidiform mole and mesenchymal dysplasia. Three patients in 14 (21%) delivered a healthy child. In only one case, delivery occurred after 37 weeks of gestation. Seven patients (50%) had a diagnosis of GTN. No patient had fatal evolution. Clinical events, such as vaginal bleeding, pre-eclampsia or hyperthyroidism, had no effect on the evolution to GTN. Continuation of the pregnancy did not increase the risk of GTN. CONCLUSION: In case of prenatal diagnosis of CHM&CF, and even if delivery of a healthy child is possible, patients should be aware of a possibly higher risk of GTN than in CHM.


Subject(s)
Hydatidiform Mole/diagnosis , Pregnancy Complications, Neoplastic/diagnosis , Pregnancy Outcome , Twins , Uterine Neoplasms/diagnosis , Adult , Female , Gestational Trophoblastic Disease/epidemiology , Humans , Pregnancy , Retrospective Studies , Risk Factors , Ultrasonography, Prenatal
9.
Fertil Steril ; 90(6): 2416-8, 2008 Dec.
Article in English | MEDLINE | ID: mdl-18191845

ABSTRACT

OBJECTIVE: To reestablish uterovaginal continuity using a total laparoscopic procedure in Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome with a functioning right horn. DESIGN: Case report. SETTING: University hospital of Hotel Dieu de Lyon. PATIENT(S): A 13-year-old woman with cyclic abdominal pain. We diagnosed MRKH syndrome with cyclic pain due to a hematometra in a functioning right horn associated to a right hematosalpinx and a nonfunctioning left horn. INTERVENTION(S): Reestablishing uterovaginal continuity with excision of the left rudimentary horn via a total laparoscopic procedure. MAIN OUTCOME MEASURE(S): Restoring regular menstruation. RESULT(S): After total laparoscopic uterovaginal anastomosis and excision of the left nonfunctioning horn, the patient's menstruation resumed 3 months later, and regular, unimpeded menstrual flow was still present at the 2-year-follow-up evaluation. CONCLUSION(S): Total laparoscopic reestablishment of uterovaginal continuity in MRKH syndrome with a functioning horn is a valuable alternative to the currently recommended treatment (laparotomy and radical excision of the rudimentary uterus).


Subject(s)
Abnormalities, Multiple/surgery , Gynecologic Surgical Procedures/methods , Laparoscopy , Uterus/surgery , Vagina/surgery , Abnormalities, Multiple/physiopathology , Adolescent , Anastomosis, Surgical , Female , Humans , Menstruation , Syndrome , Treatment Outcome , Uterus/abnormalities , Uterus/physiopathology , Vagina/abnormalities , Vagina/physiopathology
10.
Am J Obstet Gynecol ; 196(2): 172.e1-5, 2007 Feb.
Article in English | MEDLINE | ID: mdl-17306669

ABSTRACT

OBJECTIVE: The objective of the study was to describe women registered at the new French Trophoblastic Disease Reference Center and particularly the rates of gestational trophoblastic neoplasia (GTN) after molar pregnancies. STUDY DESIGN: Epidemiological data from a prospective cohort of women registered between November 1999 and November 2004 were analyzed. RESULTS: Four hundred forty-eight women were registered. The referent pathologist reclassified 32% and 5% of assumed partial mole (PM) and complete mole (CM), respectively. GTN developed in 30 of 212 patients with singleton CM (14%) and in 5 of 108 with singleton PM (5%). Among 131 patients with GTN (35 women followed up after registration for a mole and 96 registered for a GTN), 115 (88%) were low-risk and 16 (12%) were high-risk patients according to 2000 International Federation of Gynecology and Obstetrics (FIGO) scoring system. CONCLUSION: Creation of trophoblastic disease reference centers is desirable to improve treatment of patients. Our results will have to be compared with future publications based on the new 2000 FIGO oncology committee recommendations.


Subject(s)
Hospitals, Special/statistics & numerical data , Hydatidiform Mole/complications , Trophoblastic Neoplasms/epidemiology , Uterine Neoplasms/epidemiology , Adolescent , Adult , Female , France , Gestational Trophoblastic Disease/epidemiology , Gestational Trophoblastic Disease/etiology , Humans , Middle Aged , Pregnancy , Prospective Studies
11.
Breast Cancer Res Treat ; 101(2): 233-45, 2007 Jan.
Article in English | MEDLINE | ID: mdl-17061047

ABSTRACT

PURPOSE: The debate concerning poorer survival for patients with breast cancer (BC) carrying a BRCA1 germline mutation is unresolved, and requires additional data from population-based studies. PATIENTS AND METHODS: We followed 232 women with invasive BC under age 46, ascertained prospectively through a French population-based BC registry and tested for BRCA1/2 mutations (median follow-up: 82 months). We compared tumour characteristics and survival rates between 21 BRCA1/2 deleterious mutation carriers and 211 non-carriers. RESULTS: As compared to sporadic tumours, BRCA1/2 tumours showed higher grade (P = 0.02), fewer ductal carcinoma in situ (P = 0.02), more frequent medullary histology (P = 0.02), more frequent negative oestrogen and progesterone receptors (P = 0.001 each). At 5 years, BC-specific survival, metastasis-free survival, ipsilateral recurrence-free survival and contralateral BC-free survival rates for BRCA1/2 mutation carriers were 95.0%, 94.7%, 100% and 90.0% respectively, compared with 89.6%, 78.2%, 88.8% and 94.4% respectively, for non-carriers (not significant). Rates for women carrying only a BRCA1 mutation were 93.3%, 93.3%, 100%, 86.7%, respectively. 76% of BRCA1/2 carriers received chemotherapy. CONCLUSION: Despite unfavourable tumour features, we found no evidence for poorer short-term survival in BRCA1 mutation carriers compared to non-carriers in this prospective population-based cohort. The high rate of BRCA1 carriers who received chemotherapy for their BC should question the positive impact of this treatment, as suggested by preclinical studies showing increased chemosensitivity of BRCA1-associated tumours.


Subject(s)
Breast Neoplasms/genetics , Breast Neoplasms/mortality , Genes, BRCA1 , Genes, BRCA2 , Genetic Predisposition to Disease , Adult , Breast Neoplasms/pathology , Carrier State , Female , Humans , Middle Aged , Mutation , Prognosis , Survival Analysis
12.
Gynecol Oncol ; 102(1): 103-10, 2006 Jul.
Article in English | MEDLINE | ID: mdl-16624388

ABSTRACT

OBJECTIVE: Gestational trophoblastic diseases (GTD), a group of rare placenta disorders, have a varying potential for invasion, either local, or remote under the form of metastases, and are definitely cured by chemotherapy in 85 to 99% of cases. Single-agent methotrexate is the usual primary treatment for women with low-risk trophoblastic tumors (TT), yet various regimens are currently used worldwide. We reviewed these regimens and the available evidence for evaluating their respective efficacy and tolerance. METHODS: We performed an exhaustive literature search and applied the French agency for evaluation in healthcare (HAS) methodology for critical appraisal and level of evidence. We summarised the protocols used in the selected studies and their respective results regarding efficacy and toxicity. RESULTS: We selected 18 original studies on the efficacy and tolerance of methotrexate used alone or in association with folinic acid for the treatment of nonmetastatic or low-risk metastatic trophoblastic tumors. Among these 18 studies, 15 were retrospective series, 3 were prospective series without any control group, and none were controlled clinical trial. We identified four main chemotherapy regimens and two very different strategies for repeating the treatment courses. It was not possible to perform a meta-analysis due to the lack of controlled clinical trials. Because all studies were observational with no control group and methods were heterogeneous for scoring women, setting criteria for starting therapy, defining remission, and collecting information on adverse events, we found no objective element allowing recommending one protocol rather than another. CONCLUSION: Objective comparison should be addressed in the scope of comparative trials organised at the national or even international level. However their feasibility is highly problematic for rare diseases such as GTD. International collaborative works should be encouraged to reduce practice variations and allow a better comparability between strategies.


Subject(s)
Antimetabolites, Antineoplastic/administration & dosage , Gestational Trophoblastic Disease/drug therapy , Methotrexate/administration & dosage , Choriocarcinoma/drug therapy , Clinical Trials as Topic , Female , Humans , Pregnancy
13.
Prog Urol ; 15(3): 498-500, 2005 Jun.
Article in French | MEDLINE | ID: mdl-16097157

ABSTRACT

Bladder endometriosis is a rare site of a disease with very polymorphic clinical signs. The authors report the case of a 30-year-old woman operated for bladder endometriosis who presented with recent menstrual macroscopic haematuria with primary infertility and deep dyspareunia. Histological examination demonstrated bladder endometriosis sparing the urothelium. Comparison with our histological series of bladder endometriosis demonstrated polymorphic lesions ranging from integrity to complete loss of the bladder mucosa, with no correlation with clinical features.


Subject(s)
Endometriosis/pathology , Urinary Bladder Diseases/pathology , Adult , Dyspareunia/etiology , Endometriosis/surgery , Female , Hematuria/etiology , Humans , Infertility, Female/etiology , Urinary Bladder Diseases/surgery
14.
Genes Chromosomes Cancer ; 43(4): 404-13, 2005 Aug.
Article in English | MEDLINE | ID: mdl-15887246

ABSTRACT

The prevalence of BRCA1/2 germ-line mutations was assessed in a prospective population-based series of early-onset breast cancer (BC) patients in France, and the usefulness of a clinical assessment of hereditary BC risk, based on multiple criteria including pedigree structure, was evaluated. Through the Rhone region BC registry, 232 women diagnosed with BC before 46 years of age were included. They were tested for BRCA1/2 mutations an average of 10 months after diagnosis. All the women were classified according to their family history of cancer: high risk of hereditary breast cancer (HBC), low risk of HBC, isolated BC, and unknown HBC risk. Deleterious mutations were observed in 21 women (9.1%): 15 (6.5%) BRCA1 and 6 (2.6%) BRCA2. Mutations were more prevalent in women who developed BC before age 41 than in women who developed BC between ages 41 and 45 (12.8% versus 5.2%, respectively, P = 0.04). A high prevalence of BRCA1/2 mutations was found among women in the high-risk category with particular family features (i.e., small family size, predominantly male pedigree, specific cancers; 23.5%) and among women with isolated BC before age 41 and with five or fewer close adult female relatives (16.6%). According to the 10% probability level recommended by the American Society of Clinical Oncology guidelines for genetic testing of cancer, BRCA1/2 mutation screening should be considered for all women diagnosed before age 41, except for those with isolated BC in a large pedigree including multiple unaffected female relatives. The clinical assessment of HBC risk that we have developed should help in the decision to perform genetic testing.


Subject(s)
Breast Neoplasms/genetics , Genes, BRCA1 , Genes, BRCA2 , Genetic Predisposition to Disease , Germ-Line Mutation , Adolescent , Adult , Breast Neoplasms/epidemiology , Female , France , Humans , Middle Aged , Models, Genetic , Pedigree , Penetrance , Prospective Studies , Risk
15.
Fetal Diagn Ther ; 19(4): 305-12, 2004.
Article in English | MEDLINE | ID: mdl-15192288

ABSTRACT

The therapeutic field of in utero transplantation of stem cells, into human fetuses, has developed since 1988 with the hope of improved probability of engraftment and tolerance, due to immune immaturity of the host. Fifteen years later, it is possible to evaluate the results that we and others have obtained in the treatment of several fetal diseases. Seven fetal patients have been treated in Lyon: In 2 cases, pregnancy termination was induced by the in utero injection; in the 5 other cases, engraftment was obtained and repeatedly documented with presence of donor HLA antigens and/or Y chromosome in recipients. In the 2 patients with combined immunodeficiency disease, a sustained reconstitution of immunity was obtained as a result of the transplant but other complications occurred thereafter. In patients with thalassemia major, Niemann-Pick disease or hemophilia, a very partial and very transitory benefit was only obtained. Approximately 33 other patients with immunodeficiencies, hemoglobinopathies or inborn errors of metabolism have been treated worldwide, over the last 13 years, with a comparable method, using parental or fetal stem cells transplanted in utero. Successful treatment has usually been recorded in immunodeficiencies, and insufficient results have been obtained in the other cases. This form of treatment can therefore be recommended after prenatal diagnosis of combined immunodeficiency but additional research is required to improve the degree of engraftment, the lack of resistance of the host and the 'space' available for hematopoiesis in the other conditions.


Subject(s)
Fetal Therapies/statistics & numerical data , Stem Cell Transplantation/statistics & numerical data , Animals , Female , Fetal Diseases/diagnostic imaging , Fetal Diseases/surgery , Fetal Therapies/methods , Hemoglobinopathies/diagnostic imaging , Hemoglobinopathies/surgery , Humans , Pregnancy , Prenatal Diagnosis/methods , Prenatal Diagnosis/statistics & numerical data , Stem Cell Transplantation/methods , Time , Ultrasonography
16.
Fertil Steril ; 80(3): 600-6, 2003 Sep.
Article in English | MEDLINE | ID: mdl-12969705

ABSTRACT

OBJECTIVE: To assess the functional outcome and sexuality of patients after creation of a sigmoid neovagina. DESIGN: Clinical study performed between 1992 and 2002, with a mean follow-up of 3.3 years (range, 6 months to 9 years). SETTING: Tertiary care center. PATIENT(S): Sixteen consecutive patients with Rokitansky syndrome. INTERVENTION(S): Creation of a neovagina with an antiperistaltic (n = 13) or isoperistaltic (n = 3) sigmoid graft and colovestibular anastomosis by interrupted suture (n = 11) or PCEEA forceps (n = 5). All patients had a neovaginal vault suspension (n = 16). MAIN OUTCOME MEASURE(S): Functional results were evaluated in patients 6 or more months after the operation (n = 12) by using the standardized Female Sexual Function Index (FSFI). This index assesses four domains of sexual dysfunction: desire disorder, arousal disorder, orgasm disorder, and sexual pain disorder. Lubrification and "sexual" quality of life was also evaluated. Normal patients had a mean full FSFI score of 30 +/- 5 of 36. RESULT(S): The mean full FSFI score was 28 +/- 5 (range: 22-34). Seventy-two percent of patients had vaginal intercourse at least once a week; in this subset, the mean full FSFI score was 30 +/- 3 (range: 25-34). CONCLUSION(S): Sigmoid neovagina allowed a normal sexual life in patients who had sexual relations.


Subject(s)
Colon, Sigmoid/transplantation , Sexuality , Surgically-Created Structures , Uterus/abnormalities , Vagina/abnormalities , Vagina/surgery , Adolescent , Adult , Anxiety/etiology , Body Fluids/metabolism , Dyspareunia/etiology , Dyspareunia/physiopathology , Female , Humans , Infertility, Female/psychology , Libido , Orgasm , Self Concept , Surgically-Created Structures/adverse effects , Surveys and Questionnaires , Syndrome , Treatment Outcome , Vagina/metabolism
17.
Drugs ; 63(5): 463-92, 2003.
Article in English | MEDLINE | ID: mdl-12600226

ABSTRACT

Chlormadinone acetate, cyproterone acetate and dienogest are potent, orally active progestogens, which have antiandrogenic instead of partial androgenic activity. They act mainly by blocking androgen receptors in target organs, but also reduce the activity of skin 5alpha-reductase, the enzyme responsible for converting testosterone to the more potent androgen, 5alpha-dihydrotestosterone, in sebaceous glands and hair follicles. Chlormadinone acetate and cyproterone acetate also suppress gonadotropin secretion, thereby reducing ovarian and adrenal androgen production. Combined oral contraceptives (COCs) containing antiandrogenic progestogens provide highly effective contraception (gross and adjusted Pearl indices: 0-0.7 and 0-0.3, respectively) with excellent cycle control. Furthermore, COCs containing 2mg of chlormadinone acetate or cyproterone acetate plus 30 or 35 microg of ethinylestradiol produced improvement or resolution of seborrhoea in 80% of users, acne in 59-70%, hirsutism in 36% and androgen-related alopecia in up to 86%. These COCs are generally well tolerated, the main adverse effects being nonspecific or as expected for a COC (headache, breast tenderness and nausea). They have no clinically relevant effects on metabolic or liver functions or on bodyweight. Effects on mood and libido are uncommon (<3.5% and <6% of women, respectively). COCs containing antiandrogenic progestogens are likely to be particularly valuable in women with pre-existing androgen-related disorders who require contraception. They also increase the choice of products available for women with normal skin and hair who are concerned about the possibility of developing seborrhoea or acne with other COCs.


Subject(s)
Androgen Antagonists/pharmacology , Nandrolone/analogs & derivatives , Progesterone Congeners/pharmacology , Progestins/pharmacology , 5-alpha Reductase Inhibitors , Acne Vulgaris/drug therapy , Alopecia/drug therapy , Androgen Antagonists/adverse effects , Androgen Antagonists/pharmacokinetics , Animals , Chlormadinone Acetate/adverse effects , Chlormadinone Acetate/pharmacokinetics , Chlormadinone Acetate/pharmacology , Clinical Trials as Topic , Contraceptives, Oral, Synthetic/adverse effects , Contraceptives, Oral, Synthetic/pharmacokinetics , Contraceptives, Oral, Synthetic/pharmacology , Cyproterone Acetate/adverse effects , Cyproterone Acetate/pharmacokinetics , Cyproterone Acetate/pharmacology , Dermatitis, Seborrheic/drug therapy , Female , Hirsutism/drug therapy , Humans , Nandrolone/pharmacokinetics , Nandrolone/pharmacology , Progesterone Congeners/adverse effects , Progesterone Congeners/pharmacokinetics , Progestins/adverse effects , Progestins/pharmacokinetics , Receptors, Androgen/drug effects , Receptors, Androgen/physiology
18.
Bull Cancer ; 89(4): 430-6, 2002 Apr.
Article in French | MEDLINE | ID: mdl-12016043

ABSTRACT

Primary peritoneal tumors are rare and yet not well-known malignancies. We report here the clinical cases of 8 patients who were referred to our institution with a primary peritoneal tumor, 4 serous carcinomas (PSC) and 4 malignant mesotheliomas (PMM). Diagnosis was available in all cases and reviewed by two pathologists. A battery of various immunomarkers contributed to confirm the morphological diagnosis. All patients underwent initial surgery with or without optimal debulking. All of them received a platinum-based systemic chemotherapy. Intraperitoneal treatment with cisplatin and hyperthermia was performed in two cases. Four patients are dead (3 PSC, 1 PMM), two are alive (one in partial remission (1 PSC) and one is having treatment (1 PMM)), one is in complete remission (1 PMM) and one is lost to follow up (1 MMP). PSC and PMM are difficult to distinguish since they share the embryonic cOElomic epithelium as a common origin. The clinical presentations are similar and usually include the detection of a pelvic mass and/or diffuse peritoneal carcinomatosis with or without malignant ascites. Therefore, the accuracy and reliability of the initial histological examination is of crucial importance. Further attempts will be required to better identify the most active therapeutic post-surgical combinations, especially for PMM.


Subject(s)
Cystadenocarcinoma, Serous/pathology , Mesothelioma/pathology , Peritoneal Neoplasms/pathology , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Biomarkers, Tumor/analysis , Combined Modality Therapy , Cystadenocarcinoma, Serous/complications , Cystadenocarcinoma, Serous/therapy , Female , Humans , Male , Mesothelioma/complications , Mesothelioma/therapy , Middle Aged , Peritoneal Neoplasms/complications , Peritoneal Neoplasms/therapy
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