[Endometrial cancer in HNPCC syndrome]. / Cancer de l'endomètre du syndrome HNPCC Actualisation des données.

The Hereditary Non-Polyposis Colorectal Cancer syndrome (HNPCC) has initially been described as a predisposition to colorectal cancers (CRC). Subsequently, other cancers, such as endometrial cancers (EC), have been added. The objective of this review was to update data on endometrial cancers of HNPCC syndrome. Endometrial cancers of the HNPCC syndrome are characterized by a younger age at diagnosis (46-48 year old), and a higher cumulative risk along life (30% at 70 years). Complex atypical hyperplasia seems to occur before the cancer, but the transition between precursors and cancer seems to be short. Histology of endometrial cancers of the HNPCC syndrome appears quite similar to that of sporadic cases, except for non-endometrioid lesions which seem more frequent and could occur in younger women. Screening of endometrial cancer in predisposed women should associate annual clinical examination, transvaginal sonography and endometrial sampling. Unfortunately, available data on screening by sonography show that this test seems poorly accurate, with no asymptomatic cancer or hyperplasia recognized and interval cancers between screenings. Endometrial biopsy appears as the most interesting method, since 11 asymptomatic cancers and 14 hyperplasia have been diagnosed in 175 mutation carriers. Diagnostic hysteroscopy seems also interesting, but requires further evaluation. Prophylactic hysterectomy confers a complete protection against endometrial cancer. However, perioperative morbidity (especially in women with history of colorectal surgery) and long-term effects of ovarian suppression should also be considered. Screening of endometrial cancer remains the main objective of the management of those patients. Endometrial biopsy should have a larger place.

[Use of peak systolic velocity of the middle cerebral artery in the management of fetal anemia due to fetomaternal erythrocyte alloimmunization]. / Intérêt pratique du pic systolique de vélocité à l'artère cérébrale moyenne dans la prise en charge des anémies foetales par allo-immunisation érythrocytaire.

OBJECTIVE: To assess the peak systolic velocity in the middle cerebral artery (PSV-MCA) in the prediction of fetal anemia in case of severe red-cell alloimmunization. METHODS: A prospective study, from January 2003 to April 2006, of 47 consecutive pregnancies with severe alloimmunization. Fetal surveillance was based on titration and dosage of antibodies, ultrasound scans, and doppler for PSV-MCA measurement up to twice a week. A fetal blood sampling and in utero transfusion was performed in case of increase in PSV-MCA above 1.5 multiples of the median (MoM), and/or signs of hydrops on ultrasound. Severe fetal anemia was defined by fetal hemoglobin below 0.55MoM for gestational age. Analyses performed included the correlation between PSV-MCA and fetal hemoglobin, the value of PSV-MCA in the prediction of severe fetal anemia, and the determination of adequate threshold for intervention based on ROC curve analysis. RESULTS: Four hundred and eighty-five PSV-MCA were performed in 47 high-risk pregnancies, of which 125 were coupled with hemoglobin measurement by fetal blood sampling. There is a significant negative correlation between PSV-MCA and fetal hemoglobin (R2=0.6545 ; p<0.0001). Based on all prospective data, the negative predictive value of PSV-MCA was 97.8 %, sensitivity was 86.7 %, with a false positive rate of 12.2%. Area under the ROC curve was 0.85 (IC 95 %, 0.742-0.927 ; p<0.0001), suggesting an excellent value of this test. When switching the threshold for intervention from 1.5 to 1.6MoM, the positive predictive value increased, without decrease in sensitivity or negative predictive value. CONCLUSION: This study confirms the correlation between PSV-MCA and fetal hemoglobin. It allows a decrease of invasive procedures in the follow-up of pregnancies with severe red-cell alloimmunization.

Familial invasive breast cancers: worse outcome related to BRCA1 mutations.

PURPOSE: Although all studies confirm that BRCA1 tumors are highly proliferative and poorly differentiated, their outcomes remain controversial. We propose to examine, through a cohort study, the pathologic characteristics, overall survival, local recurrence, and metastasis-free intervals of 40 patients with BRCA1 breast cancer. PATIENTS AND METHODS: A cohort of 183 patients with invasive breast cancer, treated at the Institut Curie and presenting with a familial history of breast and/or ovarian cancer, were tested for BRCA1 germ-line mutation. Tumor characteristics and clinical events were extracted from our prospectively registered database. RESULTS: Forty BRCA1 mutations were found among the 183 patients (22%). Median follow-up was 58 months. BRCA1 tumors were larger in size (P =.03), had a higher rate of grade 3 histoprognostic factors (P =.002), and had a higher frequency of negative estrogen (P =.003) and progesterone receptors (P =.002) compared with non-BRCA1 tumors. Overall survival was poorer for carriers than for noncarriers (5-year rate, 80% v 91%, P =.002). Because a long time interval between cancer diagnosis and genetic counseling artificially increases survival time due to unrecorded deaths, the analysis was limited to the 110 patients whose diagnosis-to-counseling interval was less than 36 months (19 BRCA1 patients and 91 non-BRCA1 patients). The differences between the BRCA1 and non-BRCA1 groups regarding overall survival and metastasis-free interval were dramatically increased (49% v 85% and 18% v 84%, respectively). Multivariate analysis showed that BRCA1 mutation was an independent prognostic factor. CONCLUSION: Our results strongly support that among patients with familial breast cancer, those who have a BRCA1 mutation have a worse outcome than those who do not.

Clinical and biological characteristics of breast cancers in post-menopausal women receiving hormone replacement therapy for menopause.

The paradox of an excess breast cancer incidence among current users of hormone replacement therapy (HRT) without excess in breast cancer mortality raises the question of possible differences in the clinical and biological characteristics of cancers in current HRT users compared to non-users. A consecutive series of 129 post-menopausal patients under HRT for at least 6 months, in whom an operable breast cancer was diagnosed from January 1992 to December 1996, were identified retrospectively. In most cases women had received combination HRT (estrogen and progestative) and the mean duration was 60.4 (range: 6-360) months. Breast cancers diagnosed in post-menopausal patients during 1992-1993 at the Institut Curie constituted the reference series. Cancers in patients receiving HRT were smaller: 78% versus 32% T1 and 12 mm in larger diameter versus 29.5 mm. They were also more often diagnosed radiologically (49 versus 33%). A second group of 420 post-menopausal breast cancer patients whose samples had been referred for steroid hormone receptor and flow cytometric analysis in 1992-1996 were used for comparing biological and pathological information. Cancers of patients receiving HRT tended to be more often grade I and rarely grade III in the Scarf Bloom Richardson classification. Percentage of cells in S-phase as measured by flow cytometry was considerably lower in HRT users compared to control (mean 2.4 versus 3.7, median 2.2 versus 2. 6). Lymph node invasion, ploidy, and steroid hormone receptor expression did not differ significantly between the 2 groups. This apparently more favourable phenotype of breast cancers diagnosed in post-menopausal patients receiving HRT compared to unselected non-HRT users was not confirmed when analysis was restricted to breast cancers of less than 25 mm in diameter. If, as expected, the phenotypic information bears out in terms of prognosis, this may contribute to overcome the reticence in prescribing HRT due to the increased risk of breast cancer. However, it is still not clear whether the biologically less aggressive phenotype is related to the hormone treatment or is simply due to early detection.

Preservation versus section of intercostal-brachial nerve (IBN) in axillary dissection for breast cancer--a prospective randomized trial.

AIMS: Preservation of the intercostal-brachial nerve is advocated to reduce side effects of axillary dissection for breast cancer. We conducted a prospective randomized trail to compare functional results: sensory deficit and/or shoulder pain in preserved (group I) vs sacrificed (group II) intercostal-brachial nerve (IBN). METHODS: From July 1993 to April 1994, 128 patients presenting with an invasive operable breast cancer were operated on by mastectomy n = 28 or lumpectomy n = 100 and axillary dissection. The patients were eligible for randomization when the IBN was preserved at the end of the axillary dissection. Group I (nerve preservation) included 66 patients and group II (nerve section) 62 patients. RESULTS: The two groups were well balanced for TNM, type of surgery, number of nodes dissected and positive, post-operative adjuvant treatment. Examinations were conducted at 3, 6 and 12 months after surgery. Sensory deficit in the IBN area was reported by one patient in group I and four patients in group II, at 3 months (P = 0.36, NS). No patients, apart from one in group II, reported functional trouble at 18 months. Major shoulder motion, limitation and pain developed in four patients in group I and three in group II (NS). This was attributed to depression and treated adequately. Analysis of sensory deficit was impossible in these patients. CONCLUSIONS: Conservation of the IBN, while anatomically preferable, is not functionally necessary during axillary dissection for breast cancer.

Hysterectomy with adnexectomy. Can operative laparoscopy offer advantages?

OBJECTIVE: To investigate whether laparoscopic surgery has the advantage of reducing the rate of laparotomies when a patient with no genital prolapse needs a total hysterectomy associated with unilateral and bilateral adnexectomy. STUDY DESIGN: Retrospective study carried out between January 1993 and December 1995. All patients (96) with no prolapse, pelvic floor relaxation or stress urinary incontinence and scheduled for total hysterectomy with adnexectomy were included in the study. RESULTS: Laparotomy was required in 12.5% of cases (12 patients). For the 84 patients (87.5%) who underwent laparoscopic hysterectomy, the mean duration of the operation was 142.6 +/- 33.9 minutes, and the mean uterine weight was 209.7 +/- 129.4 g. The rate of laparotomy dropped steadily as the surgeon acquired experience. Whereas the rate of laparotomy was 30.5% (7 patients) in 1993, it was 10.8% (4 patients) in 1994 and fell to 2.8% (1 patient) in 1995. CONCLUSION: When adnexectomy needs to be performed with hysterectomy, in the majority of cases it should be carried out by laparotomy. Operative laparoscopy enables the rate of laparotomy to be reduced to < 15%. The existence of an adnexal mass not suspected to be malignant indicates operative laparoscopy.

[Pseudotumoral tuberculosis of the cervix]. / Tuberculose pseudo-tumorale du col de l'utérus.

Cervical tuberculosis is a rare pathology, which can clinically look like a cervix cancer. The biopsy re-establishes the right diagnosis. The treatment is medical. The prognosis is primarily the infertility due to frequent associated general genital tuberculosis.

[Poor vaginal access: excellent indication for laparoscopic hysterectomy]. / La mauvaise accessibilité vaginale: excellente indication de la coeliochirurgie pour réaliser une hystérectomie.

OBJECTIVE: The great majority of hysterectomies in patients without previous vaginal delivery have been carried out via laparotomy. The purpose of this study was to establish whether laparoscopic surgery can be of use in an attempt to reduce the number of laparotomies for patients with no previous vaginal delivery who underwent an hysterectomy indicated for benign pathologies. STUDY DESIGN: A retrospective study was carried out on 116 patients who had not had a previous vaginal delivery who underwent hysterectomy from January 1993 to December 1996. RESULTS: Laparotomy was required for only 20.7% of cases (24 patients). For the 92 patients (79.3%) who underwent laparoscopic hysterectomy, the average duration of the operation was 145 +/- 44 min (range: 60-290) and the mean uterine weight was 200 +/- 130 g (range: 30-840). CONCLUSIONS: These results demonstrate that laparoscopic surgery decreased significantly the number of laparotomies necessary for patients without previous vaginal delivery who require hysterectomy. When vaginal access is poor, simple laparoscopic preparation is inadequate and the only possibility of avoiding laparotomy is to carry out the hysterectomy entirely via laparoscopic route.

[Total hysterectomy for benign pathologies. Laparoscopic surgery does not seem to increase the risk of complications]. / Hystérectomie totale pour pathologies bénignes. La coeliochirurgie ne semble pas majorer le risque de complications.

OBJECTIVE: To assess the risk of complications of total laparoscopic hysterectomy (TLH). SETTING: University Hospital, Surgical Gynecological team. DESIGN: Retrospective study of 313 patients. For all the patients a total laparoscopic hysterectomy was performed. Every part of the operation was carried out via laparoscopy, from the adnexal phase (conservative or radical) to the colpotomy. All hemostasis was carried out by electrosurgery (bipolar coagulation). All the instruments are reusable. RESULTS: The rate of conversion to laparotomy was 6.7% (21 patients). For the patients who underwent a TLH (292 cases; 92.3%) the overall complication rate was 9.95% (29 patients). The rate of patients presented a complication which required a further operation was 1.4% (4 patients). The rate of patients presented a complication which required a re-hospitalization was 2.0% (6 patients). The rate of major urinary injury was 2.5% (6 cases): bladder injury (4 patients; 1.35%); vesico-vaginal fistula (1 case; 0.35%); ureteral complication (1 case; 0.35%). The rate of postoperative febrile morbidity was 5.8% (17 patients). CONCLUSIONS: These encouraging results mean that, provided the surgeons are experienced in laparoscopic surgery, total laparoscopic hysterectomy technique would appear not to have a higher rate of complications than hysterectomy via laparotomy or the vaginal route.

[Stenosis caused by mechanical colorectal anastomosis. Technique of plasty]. / Sténose d'anastomose colorectale mécanique. Technique de plastie.

Stenosis occurs in 1.2 to 4% of the cases after colorectal anastomosis, especially after stapling. Ischaemia may have been favoured in our two cases. Treatment requires endoscopic dilatation or section of a sclerous diaphragm and may entail reconstruction of the anastomosis. The Kraske plasty is a simple and rapid procedure (case n. degree 1) and can be performed via endoluminal access (case n. degree 2) using a linear suture.

Bladder injuries during total laparoscopic hysterectomy: diagnosis, management, and prevention.

Based on a series of 150 total hysterectomies carried out via laparoscopy between January 1993 and December 1994, we observed 2 bladder complications: 1 bladder injury and 1 vesicovaginal fistula. These two accidents form the basis of discussion on the risk factors for these complications, their diagnosis, treatment, and prevention.

Risk of invasive breast cancer after lobular intra-epithelial neoplasia: review of the literature.

OBJECTIVE: Lobular intra-epithelial neoplasia (LIN) is a rare breast disease that has been regarded alternately as a risk factor for invasive breast cancer in both breasts or a true breast cancer precursor. The controversy is largely dependent on the estimation of the IBC (Invasive Breast Cancer) risk after LIN; however a systematic review of the published data has not been previously performed. We aimed to review the IBC after LIN and the characteristics of those cancers. METHODS: A PubMed search was performed to identify the published articles in English addressing the breast cancer risk after LIN. RESULTS: There was a wide range in the figures estimating the risk of the breast cancer among the 22 studies that form the basis of this review. The cumulative average risk of invasive breast cancer (IBC) was 8.7% (range 0-33). It was 4.7% (range 0-25) for the ipsilateral and 4.2% (range 0-16) for the contralateral breast. 52% of the breast cancers occurred more than 10 years after the initial LIN. A lobular histotype was present in 30% (range 0-67%) of all IBC. CONCLUSIONS: LIN should be considered both as a risk factor (low and similar level of IBC risk for both breasts, long delay between LIN and IBC) and a precursor for IBC (over-representation of lobular histotype).

[Lobular intra-epithelial neoplasia: atypical lobular hyperplasia and lobular carcinoma in situ]. / Néoplasies lobulaires intra-épithéliales: hyperplasie lobulaire atypique et cancer lobulaire in situ.

OBJECTIVE: To review main knowledge about lobular intra-epithelial neoplasia with special interest for daily practice management. MAIN RESULTS: Intra-epithelial lobular neoplasias (ILN) are non invasive proliferations within the terminal ducto-lobular unit of monomorphic loosely cohesive small cells. A lack of expression of the E-cadherin adhesion molecule is often observed as in invasive lobular breast cancer. ILN are infrequent, however, a rise in incidence partly, due to the generalization of mammographic screening, is observed. Actually ILN are usually asymptomatic and diagnosed after breast biopsy for unspecified microcalcifications. ILN are associated with an increased risk of breast cancer that persists over 20 years after the initial diagnosis. The average risk is 4.2 % for the ipsilateral breast and 3,5 % for the controlateral breast. However, a great variability in the risk estimation is observed between the studies. There is no consensus on how to treat ILN. Surgical options have varied from biopsy to bilateral mastectomy. Current tendency is favouring lumpectomy.

[Institutional review board of the French college of obstetricians and gynecologists (CEROG).]. / Le Comité d'éthique de la recherche en obstétrique et gynécologie (CEROG).

OBJECTIVE: To report the rules and the activity of the institutional review board of the French college of obstetricians and gynecologists (Comité d'éthique de la recherche en obstétrique et gynécologie [CEROG]) created in 2008. The submission requirements are also described. METHODS: Retrospective study. RESULTS: The Ethical Review Committee [institutional review board of the French college of obstetricians and gynecologists (CNGOF)] CEROG have examined 65 project studies in 2008. The median number of submitted studies was 5.5 per month (IQR: 3.75-6.25). The origins of the submission were as follows: tertiary care university hospitals (n=63, 97 %), Inserm (n=1), INRA (n=1). Researches were found to be in conformity with the French laws and regulations, to conform to generally accepted scientific principles and medical research ethical standards in 44 cases (68 %). In 13 cases (20 %), the study has been forwarded to the Persons Protection Committee (PPC) since it concerned biomedical research or "usual care research" (soin courant). In six cases (9 %), the investigators have not responded to IRB suggestions. In two cases (3 %), the information form has been judged unsatisfactory. CONCLUSION: The CEROG is the first national IRB in obstetrics and gynecology. This new committee clarifies IRB submission procedure in France concerning non-interventional studies in the field of obstetrics and gynecology.

First-trimester ultrasound diagnosis in a recurrent case of Walker-Warburg syndrome.

We report on two siblings with Walker-Warburg syndrome (WWS) born to a consanguineous couple. In the index case, the second-trimester scan showed ventricular dilatation and we diagnosed WWS after observing retinal detachment at 26 weeks' gestation and lissencephaly by 32 weeks' gestation in addition to hypoplasia of the cerebellar vermis. The second case was first suspected at 12 weeks' gestation, when we observed a 2.8-mm nuchal translucency and an unusually large hindbrain vesicle. By 14 weeks' gestation, the lateral ventricles were clearly enlarged (12-13 mm), at 16 weeks' gestation the vitreous chamber appeared to be hyperechogenic, and by 17 weeks' gestation hydrocephalus was evident. The couple chose to continue the pregnancy, and during the third trimester lissencephaly, major hydrocephalus and polyhydramnios developed. Serial ultrasound examination should be offered to a family with a history of WWS and therefore a 1 in 4 risk of recurrence. In some cases, recurrence can be suspected as early as the first trimester, however the diagnosis cannot be excluded on the basis of normal ultrasound appearance until later in pregnancy.

Technical development and results of left extraperitoneal laparoscopic paraaortic lymphadenectomy for cervical cancer.

OBJECTIVE: The aim of this study was to describe the development of our technique for laparoscopic paraaortic lymphadenectomy for cervical cancer and to evaluate the accuracy of the left extraperitoneal route to perform complete paraaortic lymphadenectomy. METHODS: A retrospective study of a consecutive series of 44 patients with cervical cancer undergoing laparoscopic paraaortic lymphadenectomy between July 1992 and November 1998 was performed, as well as a comparison of the three routes successively used to perform paraaortic lymphadenectomy: transperitoneal, bilateral extraperitoneal, and left extraperitoneal. RESULTS: The initial choice of surgical access was transperitoneal (n = 9) in 20%, bilateral extraperitoneal (n = 14) in 32%, and left extraperitoneal (n = 21) in 48% of cases. Success rates of laparoscopic paraaortic lymphadenectomy were 78% for the transperitoneal approach, 93% for the bilateral extraperitoneal approach, and 95% for the left extraperitoneal approach. Conversion from extraperitoneal to transperitoneal laparoscopic paraaortic lymphadenectomy, because of a peritoneal tear, was necessary in 3 cases (21.4%) for the bilateral extraperitoneal route and in 3 cases (14.3%) for the left extraperitoneal route (P = 0.43). The extent of dissection varied with experience. Systematic paraaortic lymphadenectomy (up to the left renal vein) was performed via the transperitoneal route in 1 case with 19 aortic nodes removed (common iliac nodes excluded) in 160 min, via the bilateral extraperitoneal route in 6 cases with a mean of 16 +/- 2 (range: 14-19) aortic nodes removed in 153 +/- 22 min (range: 130-180), and via the left extraperitoneal route in 12 cases with a mean of 15 +/- 3 (range: 10-19) aortic nodes removed in 119 +/- 14 min (range: 100-150). There were no statistically significant differences in the total number of nodes removed between the two extraperitoneal routes, although the bilateral extraperitoneal route yielded more right-sided aortic nodes (P < 0. 01). The operating time was significantly shortened using the left extraperitoneal route (P < 0.05). CONCLUSION: Systematic paraaortic lymphadenectomy by a left extraperitoneal route is feasible. Information on right-sided aortic nodes can be obtained although the sampling is reduced compared to that of bilateral extraperitoneal route. It provides the advantages related to the use of the extraperitoneal route while reducing manipulations and thus the risk of peritoneal tearing compared to those of the bilateral extraperitoneal route.

Is total laparoscopic hysterectomy a safe surgical procedure?

Total hysterectomy via laparoscopy is a recently developed technique. Assessment of a new surgical technique, once the operation has been shown to be feasible, requires an evaluation of the risks of complications. Here we report our cumulative 3 year experience with laparoscopic hysterectomy in a total of 222 patients. The overall complication rate was 10.0%. We did not observe any haemorrhage complications requiring another operation. Four patients (1.8%) were re-admitted to hospital but only two of them (0.9%) had to be operated upon again (one vesico-vaginal fistula and one vaginal cuff wound separation). These encouraging results mean that, provided the surgeons are experienced in laparoscopic surgery, total laparoscopic hysterectomy technique would appear not to have a higher rate of complications than hysterectomy via laparotomy or the vaginal route.

Hysterectomy for patients without previous vaginal delivery: results and modalities of laparoscopic surgery.

The great majority of hysterectomies in nulliparous patients have been carried out via laparotomy. The purpose of this study was to establish whether laparoscopic surgery can be of use in an attempt to reduce the number of laparotomies when hysterectomy is indicated in patients without previous vaginal delivery. A retrospective study was carried out on 66 women who had not had a previous vaginal delivery who underwent hysterectomy from January 1993 to May 1995. Laparotomy was required for only 19.7% of cases (13 patients). For the 53 patients (80.3%) who underwent laparoscopic hysterectomy, the average duration of the operation was 152.24 +/- 45.7 min, and the average weight of the uterus was 238.3 +/- 154.1 g. The duration of the laparoscopic operation was correlated in a statistically significant fashion with the weight of the uterus (P = 0.0005), the necessity of associated procedures during the hysterectomy (P = 0.01) and the surgeons' experience (P = 0.01). These results demonstrated that laparoscopic surgery decreases the number of laparotomies necessary for patients with no previous vaginal delivery who require hysterectomy. When vaginal access is poor, simple laparoscopic preparation is inadequate and the only possibility of avoiding laparotomy is to carry out the hysterectomy entirely via the laparoscopic route.

Proximal tubal occlusion: is there an alternative to microsurgery?

Fertility outcome following microsurgical tubocornual anastomosis by laparotomy was evaluated. A total of 131 women presenting pure proximal occlusion, whether bilateral or in one tube only, were treated between January 1978 and December 1993. Subsequent fertility was studied in 120 patients, 11 being patients lost to follow-up. Cumulative intrauterine pregnancy (IUP) rate, evaluated by life-table analysis, was 68% at 24 months. The overall IUP rate, calculated from a group of 120 women with follow-up > or = 2 years, and including births and miscarriages, was 70% after 2 years. Comparisons of the cumulative IUP rates show that the fertility outcome is significantly better if the woman is aged < or = 36 years and if tubocornual anastomosis is carried out bilaterally. These results from our personal series confirm that microsurgical tubocornual anastomosis is still of prime importance in the treatment of pure proximal occlusions. Nevertheless, considerable progress in the fields of tubal catheterization, Falloposcopy and in-vitro fertilization techniques raises the question of the management of patients presenting with a proximal tubal occlusion. Here we define the indications for microsurgical tubocornual anastomosis.