[New options in the treatment of ano-rectal incontinence]. / Nouvelles options dans le traitement de l'incontinence ano-rectale.

Ano-rectal incontinence is known to affect about 2% of the population. Main risk factors are traumatic delivery and previous anal surgery. All patients should have a trial of conservative treatment. Patients with major external anal sphincter defect have a 70 to 80% improvement of their symptoms after an overlap sphincter repair Unfortunately, these results deteriorate over time. Sacral nerve modulation improves continence and quality of life in 75 to 100% of patients with various aetiologies. In case of idiopathic internal sphincter degeneration, sphincter augmentation with bulking agents seems to be the least expensive option.

[Sexual and reproductive health--specific problems in adolescence]. / Santé reproductive--problèmes spécifiques à l'adolescence.

The specificity of adolescent gynecology is uncontested and asks for a specific knowledge and approach. Even if the symptoms remain the same, differential diagnostic and therapeutic approach will be different, depending on the state of development (early puberty, late adolescence), during which they occur. The ignorance of specific pathologies (utero-vaginal malformation, ovarian pathologies related to the menstrual cycle) and therefore inadequate or retarded medical treatment might be the source of unnecessary sequellae. There are now many possibilities to acquire or improve one's knowledge and skills in this particular domain of gynecology. The medico-legal situation as well differs in many points from that of the adult.

Effects of epidural analgesia on pelvic floor function after spontaneous delivery: a longitudinal retrospective study.

The aim of the study was to assess the effects of epidural analgesia on pelvic floor function. Eighty-two primiparous women (group 1, consisting of 41 given an epidural, and group 2 of 41 not given an epidural) were investigated during pregnancy and at 2 and 10 months after delivery by a questionnaire, clinical examination, and assessment of bladder neck behavior, urethral sphincter function and intravaginal/intra-anal pressures. The prevalence of stress urinary incontinence was similar in both groups at 2 months (24% vs. 17%, P = 0.6) and 10 months (22% vs. 7%, P = 0.1), as was the prevalence of decreased sexual vaginal response at 10 months (27% vs. 10%, P = 0.08). Bladder neck behavior, urethral sphincter function and intravaginal and intra-anal pressures showed no significant differences between the two groups. Ten months after spontaneous delivery, there were no significant differences in the prevalence of stress urinary incontinence and decreased sexual vaginal response, or in bladder neck behavior, urethral sphincter function and pelvic floor muscle strength between women who had or had not had epidural analgesia.

Granular cell tumor of the breast: a diagnostic pitfall.

We report a rare case of benign granular cell tumor of the breast associated with multiple similar lesions of the scalp, the right shoulder, the right flank, the abdominal wall and the vulva, treated with wide excisions.

Colposcopic evaluation after a repeat atypical squamous cells of undetermined significance (ASCUS) smear.

OBJECTIVES: Management of patients with atypical squamous cells of undetermined significance (ASCUS) remains controversial. We chose to repeat the Pap smear after four months. If ASCUS persisted in this second test, the patient was advised to undergo colposcopy. Our objective is to determine the clinical significance and the prediction of neoplasia among these patients through a colposcopic examination. METHODS: Of 29,827 patients who had a Pap smear, ASCUS were detected in 1387 (5%) and persisted in the repeat smear of 225 (16%). Colposcopy and an additional Pap smear were performed on 186 patients. RESULTS: Out of 186 colposcopic evaluations, 91 (49%) were normal and the patients had a negative Pap smear. Colposcopy was abnormal in 95/186 patients (51%) (Table 1). Histology of the directed biopsies revealed 38 (21%) low-grade squamous intraepithelial lesions (LSIL) and 17 (9%) high-grade squamous intraepithelial lesions (HSIL). Forty patients (21%) with normal biopsies had ASCUS for the third time in the Pap smear. CONCLUSIONS: Colposcopic evaluation after a repeated Pap smear with ASCUS is an appropriate cost-effective management. Finding 30% of LSIL or HSIL justifies this additional investigation.

A low-dose stimulation protocol using highly purified follicle-stimulating hormone can lead to high pregnancy rates in in vitro fertilization patients with polycystic ovaries who are at risk of a high ovarian response to gonadotropins.

OBJECTIVE: To study the benefits of a low-dose stimulation (LDS) protocol with purified urinary follicle-stimulating hormone in patients with polycystic ovaries who have presented previously with a very high ovarian response to a standard hMG stimulation. DESIGN: Cohort study. SETTING: Fertility center in a university hospital. PATIENT(S): Sixty-one patients involved in an IVF/ICSI program from January 1995 to December 1996. INTERVENTION(S): The patients were first stimulated with a standard protocol using hMG and presented with a very high ovarian response. These patients were then stimulated a second time using a low-dose protocol. Cryopreserved embryos were transferred in later artificial or natural cycles until to December 1999. MAIN OUTCOME MEASURE(S): Number of gonadotropin ampules; estradiol level on the day of ovulation induction; follicles, oocytes, and cryopreserved zygotes; fertilization, implantation, and pregnancy rates; and number of ovarian hyperstimulation syndromes (OHSS). RESULT(S): The number of ampules used, the estradiol level reached, and the number of oocytes obtained were significantly lower under the LDS than the standard protocol. High implantation (21.8%) and clinical pregnancy (38.4%) rates were obtained after LDS. The cumulated deliveries per cycle started and per patient were, respectively, 41.6% and 52.5%. Five patients suffered OHSS with the standard protocol, and none with the LDS. CONCLUSION(S): The LDS protocol offers a safe and efficient treatment for patients who present with echographic polycystic ovaries and are at risk of an excessive ovarian response to standard IVF stimulation protocols.

Pelvic floor education after vaginal delivery.

OBJECTIVE: To assess the effect of pelvic floor education after vaginal delivery on pelvic floor characteristics in nulliparous women. METHODS: We examined 107 nulliparas during pregnancy and at 9 weeks and 10 months after vaginal delivery. Methods used included a questionnaire, clinical examination, perineosonography, urethral pressure profiles, and intravaginal and intra-anal pressure recordings during pelvic floor contraction. After the second examination, the women were assigned in alternating manner to either 12 sessions of pelvic floor exercises with biofeedback and electrostimulation (n = 51) or no training (n = 56). The two groups were compared at the third examination. RESULTS: Stress urinary incontinence incidence decreased in 2% of control subjects compared with 19% of women who underwent pelvic floor education (P =.002), whereas the incidence of fecal incontinence (5% versus 4%, P = 1) and the percentage of women who recovered predelivery pelvic floor contraction strength (33% versus 41%, P =.4) were no different. We observed no significant differences in bladder neck position and mobility, urethral functional length, maximal urethral closure pressure, pressure transmission ratio, residual area of continence at stress standing, or intravaginal or intra-anal pressures during pelvic floor contraction between groups at the third examination. CONCLUSION: Pelvic floor education, begun 2 months postpartum, significantly reduced the incidence of stress urinary incontinence, but not fecal incontinence or weak pelvic floor. Similarly, bladder neck behavior, urodynamic characteristics, intravaginal or intra-anal pressures during pelvic floor squeezing also were not modified.

Development of a well-defined medium for the in vitro maturation of immature bovine cumulus-oocyte complexes.

PURPOSE: Our purpose was to develop a well-defined medium for the in vitro maturation (IVM) of immature bovine cumulus-oocyte complexes (COC). METHODS: The COC were cultured in the presence of three protein supplementations: fetal bovine serum (FBS), bovine serum albumin, and Synthetic Serum Substitute. The embryos obtained after in vitro fertilization of IVM oocytes were cocultured with Vero cells and their development to the morula and blastocyst stages was studied. RESULTS: When FBS was absent from the IVM medium, a significantly lower fertilization rate was observed, followed by a decrease in the percentage of embryos reaching the blastocyst stage. When FBS was replaced by a defined protein supplementation, the best results were obtained with Synthetic Serum Substitute. CONCLUSIONS: Adequate protein supplementation of the IVM medium optimizes the fertilization rate and the development of bovine IVM oocytes. The implication of these results in the human field is discussed.

Nasal vaccination with attenuated Salmonella typhimurium strains expressing the Hepatitis B nucleocapsid: dose response analysis.

Nasal vaccination of mice with recombinant attenuated strains of Salmonella typhimurium is more efficient at inducing antibody responses than oral vaccination. However, mortality was observed when high doses [10(9) colony forming unit (CFU)], otherwise safe by the oral route, were administered. This observation was counterbalanced by the fact that nasal vaccination was still highly efficient with lower doses (10(6) CFU), which are inefficient by the oral route and this, without any incidents of mortality. Here, we further analyse in mice the effect of nasal vaccination with differently attenuated S. typhimurium strains expressing the Hepatitis B nucleocapsid (HBc). Surprisingly, as few as 100 CFU were sufficient to induce a maximal HBc specific antibody response, but only if the bacteria were inhaled. Furthermore, we observed no correlation between the inoculum dose and the number of surviving bacteria in cervical lymph nodes and spleen. Examination of lung sections revealed strong inflammation and bronchopneumonia 24 h after nasal vaccination with 10(8) CFU, while only minor signs of inflammation were detected transiently when 10(3) CFU or phosphate buffered saline (PBS) were administered. Our data suggest that the safety issue of nasal vaccination with low doses of the Salmonella vaccine strains should be addressed in humans, as it might be an efficient alternative to oral vaccination.

Birth trauma: short and long term effects of forceps delivery compared with spontaneous delivery on various pelvic floor parameters.

OBJECTIVE: To compare the effects of forceps delivery and spontaneous delivery on pelvic floor functions in nulliparous women. DESIGN: A longitudinal prospective study with investigations during the first pregnancy, 10 weeks and 10 months after delivery. SETTING: Antenatal clinic in a teaching hospital. POPULATION: One hundred and seven patients aged 28 +/- 4 years, divided into those with forceps (n = 25) or spontaneous (n = 82) delivery. METHODS: Investigations with a questionnaire, clinical examination, assessment of bladder neck behaviour, urethral sphincter function, intra-vaginal/intra-anal pressures during pelvic floor contractions. RESULTS: The incidence of stress urinary incontinence was similar in both groups at 9 weeks (32% vs 21%, P = 0.3) and 10 months (20% vs 15%, P = 0.6) after delivery, as was the incidence of faecal incontinence (9 weeks: 8% vs 4%, P = 0.9; 10 months: 4% vs 5%, P = 1) and the decreased sexual response at 10 months (12% vs 18%, P = 0.6). Bladder neck behaviour, urethral sphincter function and intra-vaginal and intra-anal pressures were also similar in the two groups. However, 10 months after delivery, the incidence of a weak pelvic floor (20% vs 6%, P = 0.05) and the decrease in intra-anal pressure between the pre- and post-delivery values (-17 +/- 28 cm H2O vs 3 +/- 31 cm H2O, P = 0.04) were significantly greater in the forceps-delivered women. CONCLUSIONS: Forceps delivery is not responsible for a higher incidence of pelvic floor complaints or greater changes in bladder neck behaviour or urethral sphincter functions. However, patients with forceps delivery have a significantly greater decrease in intra-anal pressure and a greater incidence of a weak pelvic floor.

Prospective randomized study of two cryopreservation policies avoiding embryo selection: the pronucleate stage leads to a higher cumulative delivery rate than the early cleavage stage.

OBJECTIVE: To compare the cumulative live birth rates obtained after cryopreservation of either pronucleate (PN) zygotes or early-cleavage (EC) embryos. DESIGN: Prospective randomized study. SETTING: University hospital. PATIENT(S): Three hundred eighty-two patients, involved in an IVF/ICSI program from January 1993 to December 1995, who had their supernumerary embryos cryopreserved either at the PN (group I) or EC (group II) stage. For 89 patients, cryopreservation of EC embryos was canceled because of poor embryo development (group III). Frozen-thawed embryo transfers performed up to December 1998 were considered. MAIN OUTCOME MEASURE(S): Age, oocytes, zygotes, cryopreserved and transferred embryos, damage after thawing, cumulative embryo scores, implantation, and cumulative live birth rates. RESULT(S): The clinical pregnancy and live birth rates were similar in all groups after fresh embryo transfers. Significantly higher implantation (10.5% vs. 5.9%) and pregnancy rates (19.5% vs. 10.9%; P< or = .02 per transfer after cryopreserved embryo transfers were obtained in group I versus group II, leading to higher cumulative pregnancy (55.5% vs. 38.6%; P < or = .002 and live birth rates (46.9% vs. 27.7%; P< or = .0001. CONCLUSION(S): The transfer of a maximum of three unselected embryos and freezing of all supernumerary PN zygotes can be safely done with significantly higher cumulative pregnancy chances than cryopreserving at a later EC stage.

[Sentinel lymph node biopsy in breast cancer: the Lausanne experience]. / La biopsie du ganglion sentinelle en cas de cancer du sein: l'expérience Lausannoise.

A total of 40 patients (mean age 51 yrs; 36-89 yrs) with clinically T1-T2(< 3 cm)N0M0 breast cancer underwent sentinel node (SN) mapping with radioactive tracer (99mTc) injection only in 21 patients, with Patent blue V in 1 patient, or with both techniques in 19 patients. The preoperative injection of 99mTc (20-40 MBq) was followed by lymphoscintigraphy. A handheld gamma probe was used to detect the SN in the operative room. A lumpectomy and an axillary dissection were performed in all the patients. SNs could be identified in 39/40 patients, resulting in a sensitivity of 98%. Successful localization of the SNs was accomplished by isotope only in 19/20 patients, by blue dye only in 1/1 patient, and by both methods in 19/19 patients; in 2 of these 19 patients, SNs were identified by blue dye only. Axillary metastases were found in 12/40 patients (30%), the SN being the only nodal metastasis in 8/12 patients (75%). Six of these 12 patients (50%) had only evidence of micrometastasis. Negative SNs on serial sections stained with hematoxylin-eosin (H&E) were evaluated with cytokeratin immunostain (C11). In all cases of negative SNs the remaining axillary nodes were also free of tumor, resulting in a negative predictive value of 100%. We conclude that SN mapping is a highly accurate method for staging the axillary node status in breast cancer patients. Optimal localization is achieved by the combination of injection of 99mTc-colloid and blue dye as evidence by the cases of positive SN identified by only one of both methods.

The morcellator knife: a new laparoscopic instrument for supracervical hysterectomy and morcellation.

BACKGROUND: Cutting the cervix, morcellation, and extraction of the uterus and myomata remain major problems in endoscopic surgery. We developed an efficient, safe, reusable, and inexpensive instrument to cut the cervix and morcellate the uterus and myomata: the morcellator knife. INSTRUMENT: The morcellator knife is a classic lancet with an interchangeable blade, transformed into an endoscopic instrument that can be inserted easily through a 10-mm-diameter trocar. The blade has an automatic retraction system and is set in the standby position, ensuring security. Cutting the cervix and uterine or myoma fragmentation are easy. The mass to be cut is held between two grasping forceps for easy cutting with the blade, under permanent visual control. After morcellation, extraction of the masses is performed through a posterior culdotomy. EXPERIENCE: We have used this morcellator knife in 54 subtotal hysterectomies and 16 myomectomies. There were no complications during the procedures. Morcellation lasted 3-14 minutes and involved the use of an average of two to three blades. CONCLUSION: The morcellator knife is a simple, safe, reusable, and inexpensive instrument with a low maintenance cost.

Effect of grade on disease-free survival and overall survival in FIGO stage I adenocarcinoma of the endometrium.

OBJECTIVE: To analyse the effect of differentiation on disease-free survival (DFS) and overall survival (OS) in patients with stage I adenocarcinoma of the endometrium. PATIENTS AND METHODS: From 1979 to 1995, 350 patients with FIGO stage IA-IC with well (G1), moderately (G2) or poorly (G3) differentiated tumors were treated with surgery and high dose-rate brachytherapy with or without external radiation. Median age was 65 years (39-86 years). RESULTS: The 5-year DFS was 88+/-3% for the G1 tumors, 77+/-4% for the G2 tumors, and 67+/-7% for the G3 tumors (P=0.0049). With regard to the events contributing to DFS, the 5-year cumulative percentage of local relapse was 4.6% for the G1 tumors, 9.0% for the G2 tumors, and 4.6% (P=0.027) for the G3 tumors. Cumulative percentage of metastasis was 1.4, 6.3 and 7.2% (P<0.001), respectively, whereas percentages of death were 6.0, 7.9 and 20.7% (P<0.001). The 5-year OS was 91+/-3, 83+/-4 and 76+/-7%, respectively (P=0.0018). In terms of multivariate hazard ratios (HR), the relative differences between the three differentiation groups correspond to an increase of 77% of the risk of occurrence of either of the three events considered for the DFS (HR=1.77, 95% CI [0.94-3.33]), (P=0.078) for the G2 tumors and of 163% (HR=2.63, 95% CI [1.27-5.43]), (P=0.009) for the G3 tumors with respect to the G1 tumors. The estimated relative hazards for OS are, respectively, in line with those for DFS: HR=1.51 (P=0.282) for the G2 tumors; and HR=3.37 (P=0.003) for the G3 tumors. CONCLUSION: Patients with grade 1 tumors are those least exposed to either local relapse, metastasis, or death. In contrast patients with grade 2 tumors seem to be at higher risk of metastasis, whereas patients with grade 3 tumors appear at higher risk of death. Since we have looked at the first of three competing events (local relapse, metastasis and death), this suggests that patients with grade 3 tumors probably progress to death so fast that local relapse, if any, cannot be observed.

Endometrial ablation for the treatment of dysfunctional uterine bleeding using balloon therapy.

Dysfunctional uterine bleeding (DUB) has emerged as one of the most frequently encountered gynecological problems. Besides the problems with anemia and iron deficiency, excessive menstrual bleeding adversely affects quality of life and contributes to health-care costs as it is a major indication for referral to the gynecological outpatient clinic. It is a disabling problem for many women and a major clinical challenge for gynecologists. There are numerous options for the treatment of DUB: drug therapy, hysterectomy, endometrial ablation with the Nd:YAG laser, resectoscope, rollerball, and more recently other alternatives such as bipolar devices, direct hot saline instillation, microwaves, and thermal balloons.

Mucosal but not parenteral immunization with purified human papillomavirus type 16 virus-like particles induces neutralizing titers of antibodies throughout the estrous cycle of mice.

We have recently shown that nasal immunization of anesthetized mice with human papillomavirus type 16 (HPV16) virus-like particles (VLPs) is highly effective at inducing both neutralizing immunoglobulin A (IgA) and IgG in genital secretions, while parenteral immunization induced only neutralizing IgG. Our data also demonstrated that both isotypes are similarly neutralizing according to an in vitro pseudotyped neutralization assay. However, it is known that various amounts of IgA and IgG are produced in genital secretions along the estrous cycle. Therefore, we have investigated how this variation influences the amount of HPV16 neutralizing antibodies induced after immunization with VLPs. We have compared parenteral and nasal protocols of vaccination with daily samplings of genital secretions of mice. Enzyme-linked immunosorbent assay analysis showed that total IgA and IgG inversely varied along the estrous cycle, with the largest amounts of IgA in proestrus-estrus and the largest amount of IgG in diestrus. This resulted in HPV16 neutralizing titers of IgG only being achieved during diestrus upon parenteral immunization. In contrast, nasal vaccination induced neutralizing titers of IgA plus IgG throughout the estrous cycle, as confirmed by in vitro pseudotyped neutralization assays. Our data suggest that mucosal immunization might be more efficient than parenteral immunization at inducing continuous protection of the female genital tract.

The nature of the attenuation of Salmonella typhimurium strains expressing human papillomavirus type 16 virus-like particles determines the systemic and mucosal antibody responses in nasally immunized mice.

We have recently shown by using a recombinant Salmonella typhimurium PhoPc strain in mice the feasibility of using a Salmonella-based vaccine to prevent infection by the genital human papillomavirus type 16 (HPV16). Here, we compare the HPV16-specific antibody responses elicited by nasal immunization with recombinant S. typhimurium strains harboring attenuations that, in contrast to PhoPc, are suitable for human use. For this purpose, chi4989 (Deltacya Deltacrp) and chi4990 [Deltacya Delta(crp-cdt)] were constructed in the ATCC 14028 genetic background, and comparison was made with the isogenic PhoPc and PhoP- strains. Although the levels of expression of HPV16 virus-like particle (VLP) were similar in all strains, only PhoPc HPV16 induced sustained specific antibody responses after nasal immunization, while all strains induced high antibody responses with a single nasal immunization when an unrelated viral hepatitis B core antigen was expressed. The level of the specific antibody responses induced did not correlate with the number of recombinant bacteria surviving in various organs 2 weeks after immunization. Our data suggest that the immunogenicity of attenuated Salmonella vaccine strains does not correlate with either the number of persisting bacteria after immunization or the levels of in vitro expression of the antigen carried. Rather, the PhoPc phenotype appears to provide the unique ability in Salmonella to induce immune responses against HPV16 VLPs.

Follow-up of 32 hypothalamo-hypopituitary patients treated with pulsatile gonadotropin-releasing hormone or human menopausal gonadotropin.

In a clinical retrospective study, a follow-up of hypothalamo-amenorrheic patients treated firstly with gonadotropin-releasing hormone (GnRH) pump stimulation and secondly with human menopausal gonadotropin (hMG) was performed. Thirty-two hypothalamo-amenorrheic patients, 24-38 years old, were submitted to 103 GnRH stimulation cycles. Seven, with polycystic ovaries (PCO) on ultrasound, were stimulated with hMG after one or several unsuccessful pump cycles. Ovulation was confirmed by a luteinizing hormone (LH) surge or triggered by human chorionic gonadotropin in 80 out of 103 cycles (77.7%/cycle) leading to 62 timed sexual intercourses and 17 intrauterine inseminations (IUI). Twenty-one pregnancies (26.3%/cycle) terminated in eight abortions (38.1%/pregnancy) and 13 deliveries (40.6%/patient). hMG stimulation, in the seven PCO patients (six IVF, one IUI), led to four additional deliveries in three patients. Five patients became pregnant spontaneously after pump failure (n = 2) or unsuccessful IVF (n = 3). Combining all cycles, 17 deliveries were obtained in 16 patients. No case of ovarian hyperstimulation syndrome (OHSS) was observed. GnRH is an efficient and safe treatment of hypothalamo-amenorrheic-induced anovulation. Following GnRH or hMG ovarian stimulation, spontaneous ovulation and conception may be restored in certain hypothalamo-amenorrheic patients.