Multifaceted intervention to decrease the rate of severe postpartum haemorrhage: the PITHAGORE6 cluster-randomised controlled trial.

OBJECTIVE: Decreasing the prevalence of severe postpartum haemorrhages (PPH) is a major obstetrical challenge. These are often considered to be associated with substandard initial care. Strategies to increase the appropriateness of early management of PPH must be assessed. We tested the hypothesis that a multifaceted intervention aimed at increasing the translation into practice of a protocol for early management of PPH, would reduce the incidence of severe PPH. DESIGN: Cluster-randomised trial. POPULATION: 106 maternity units in six French regions. METHODS: Maternity units were randomly assigned to receive the intervention, or to have the protocol passively disseminated. The intervention combined outreach visits to discuss the protocol in each local context, reminders, and peer reviews of severe incidents, and was implemented in each maternity hospital by a team pairing an obstetrician and a midwife. MAIN OUTCOME MEASURES: The primary outcome was the incidence of severe PPH, defined as a composite of one or more of: transfusion, embolisation, surgical procedure, transfer to intensive care, peripartum haemoglobin decrease of 4 g/dl or more, death. The main secondary outcomes were PPH management practices. RESULTS: The mean rate of severe PPH was 1.64% (SD 0.80) in the intervention units and 1.65% (SD 0.96) in control units; difference not significant. Some elements of PPH management were applied more frequently in intervention units-help from senior staff (P = 0.005), or tended to - second-line pharmacological treatment (P = 0.06), timely blood test (P = 0.09). CONCLUSION: This educational intervention did not affect the rate of severe PPH as compared with control units, although it improved some practices.

[Audipog perinatal network. Part 1: principal perinatal health indicators, 2004-2005]. / Réseau sentinelle Audipog 2004-2005. Partie 1 : résultats des principaux indicateurs périnatals.

OBJECTIVE: To present the principal perinatal indicators for 2004-2005, based on data from the Audipog sentinel network. PATIENTS AND METHODS: The database for 2004 and 2005 covers 71,406 pregnancies from 86 maternity units throughout the year. We constructed a random subsample each year by including only the births occurring during a single month for each maternity ward. Our study therefore analyzes 6987 pregnancies in 2004 and 7648 pregnancies in 2005. RESULTS: The number of women working during pregnancy increased between 2004 and 2005 (62.3% versus 66.3%) (p=0.0008) as did the percentage with a postsecondary education (35.1% versus 41.9%) (p<0.0001). The percentage of amniocenteses declined (10.4% versus 7.9%) (p<0.0001). Use of prenatal care improved: more women had prenatal visits before week 14 (30.5% versus 33.9%) (p=0.0002), and fewer women had no prenatal care at all (1.1% versus 0.4%) (p=0.0003). The percentage of preterm deliveries was 6.4% in 2004 and 7% in 2005 (p=0.14) and the percentage of induced preterm deliveries was 37% in 2004 and 41.2% in 2005 (p=0.18). The cesarean rate was essentially stable (19 and 19.2%) and the rate of instrumental intervention in vaginal deliveries fell from 13.1% in 2004 to 11.2% in 2005 (p=0.0015). DISCUSSION AND CONCLUSION: The rates of cesarean and of preterm deliveries remained stable between 2004 and 2005, but the rate of induced preterm deliveries rose. These indicators are consistent with trends that began earlier.

[Audipog perinatal network 2004-2005. Part 2: assessment of medical practices]. / Réseau Sentinelle Audipog 2004-2005. Partie 2 : évaluation des pratiques professionnelles.

OBJECTIVE: To describe specific clinical practices in France in 2004-2005 based on data from the Audipog sentinel network. PATIENTS AND METHODS: The database for 2004 and 2005 covers 71406 pregnancies from 86 maternity units throughout the year. We constructed a random subsample each year by including only the births occurring during a single month for each maternity ward. Our study therefore analyzes 6987 pregnancies in 2004 and 7648 pregnancies in 2005. RESULTS: Among the very preterm (<33 weeks of gestation) infants from multiple pregnancies, 77.4% were born in level 3 hospitals in 2000-2001, and only 44.9% in 2004-2005 (p<0.0001). Among the very preterm infants from singleton pregnancies, the percentage born in level 3 maternity hospitals rose between 1996-1997 and 2004-2005 (55% versus 73%; p=0.001). The rate of corticosteroid therapy before delivery among very preterm infants did not change significantly between 2000 and 2005 (p=0.58). The cesarean rate rose from 14% in 1994 to 20.0% in 2005. The percentage of actively managed third stages of labor increased from 1994-1995 to 2005 (6.2% versus 31.3%). Fewer episiotomies were performed: 56% in 1994-1995 and 41.3% in 2005. Exclusive breast-feeding rose from 51.2% in 2000-2001 to 58.5% in 2005 (p<0.0001). Early discharge increased between 1994-1995 and 2005 (p<0.0001). DISCUSSION AND CONCLUSION: Indicators monitoring implementation of some of the national clinical practice guidelines have improved slightly over time, although most often before the publication of these guidelines.

[Prevention and early management of immediate postpartum haemorrhage: policies in six perinatal networks in France]. / Politiques de prévention et de prise en charge précoce de l'hémorragie du post-partum immédiat dans six réseaux de maternités françaises.

OBJECTIVES: Postpartum haemorrhage (PPH) constitutes the leading cause of maternal deaths in France, and the majority of these deaths are preventable. The objective of this study was to ascertain policies for prevention and early management of PPH in maternity units, and to compare the results with scientific evidence. The survey was part of the Euphrates European project, and was conducted in France in 2003 before national recommendations for clinical practice related to PPH were launched. MATERIALS AND METHODS: A cross-sectional declarative survey was conducted in six perinatal networks representing 132 maternity units. A postal questionnaire was sent to all units. Main outcomes measured were stated policies for prevention, diagnosis and management of PPH. RESULTS: There was no definition of PPH in one out of four units, and no written protocol for PPH management in one out of six. Policies of using preventive uterotonics were widespread, but variation was observed concerning the timing of administration, and association with the other components of active management of the third stage of labour. Policies about drugs used for management of PPH also varied. CONCLUSION: Variations in policies show firstly that evidence-based improvement in practice is possible, and secondly that further research is needed on poorly documented aspects of PPH management.

Application of the French guidelines for preventing neonatal group B streptococcal disease in a university hospital.

This study evaluated the application of the French guidelines for prevention of neonatal group B streptococcus (GBS) infections. The prevalence of GBS vaginal carriage by pregnant women during the study period was 6%. Less than 50% of pregnant women testing positive for GBS were treated with at least two doses of antibiotics during labour, and most received only one dose or no antibiotics. In addition, several neonates were colonised or infected by GBS although their mothers were GBS-negative. These results are consistent with vaginal screening having a poor sensitivity, as suggested by the low prevalence of GBS carriage.

Presence of PAF-acether in human breast carcinoma: relation to axillary lymph node metastasis.

PAF-acether (PAF; formerly platelet-activating factor), a potent lipid mediator of inflammation, is involved in multiple cellular functions. To evaluate the role of PAF in human cancer, we obtained specimens from patients with localized breast carcinoma and assayed them for PAF. PAF was found in almost all carcinoma, although it was not detected in most of the matched, nontumor breast tissue samples. Intratumor PAF level was elevated when axillary lymph node involvement was low. Greater axillary extension (two or more positive lymph nodes) was associated with a decreased intratumor PAF level. These findings, along with the independence of other prognostic factors, indicate that PAF is a tumor marker of axillary lymph node involvement.

[Report of the French "conférence nationale de l'échographie obstétricale et fœtale" (CNEOF)-- recommendations for focused prenatal ultrasound]. / Rapport de la conférence nationale de l'échographie obstétricale et fœtale (CNEOF)--recommandations pour l'échographie focalisée.

The conference has among its functions, to promote a quality assurance policy for obstetrics and foetal ultrasound scans by participating in the development of an information strategy for the professionals and the public on the interest and limits of these techniques, and in the development of rules for good practice. Thus, the conference produced in 2005 a good practice's recommendations report concerning the screening of ultrasound scans, with an actualised version in 2015, and has published in 2014 a similar report concerning second line prenatal ultrasound. The conference complements these recommendations by characterizing the third type of ultrasound scan, the "focused ultrasound scan", which is a daily tool for every practitioner in obstetrics.

How singleton breech babies at term are born in France: a survey of data from the AUDIPOG network.

Based on data from the AUDIPOG sentinel network between 1994 and 2010, we can say that the rate of singleton breech presentation at term is 3% and remains unchanged despite an external cephalic version rate of 35%. The total cesarean section rate is currently 75%. This rate increased by nearly 20% after the Hannah publication in 2000, regardless of the type of breech and type of maternity unit. The rate of planned cesarean sections increased in particular, going from 40% to 60%, and even reaching 67% for footling breech presentations. The rate is higher in type I maternity units than in type II or III. This cesarean section rate has been stable since 2005 and has even decreased for the Frank breech. The average rate of external cephalic version remains stable at around 23%. The episiotomy rate is 28%. The rate of babies transferred to neonatology units is higher for breech babies at term than for babies presenting cephalically (3.9% compared to 2.9%), but the newborns most often transferred are those born by cesarean section (4.1% compared to 3.4%).

Does paraaortic lymphadenectomy have a benefit in the treatment of ovarian cancer that is apparently confined to the ovaries?

We conducted a retrospective review of all epithelial ovarian carcinoma patients with disease that is apparently confined to the ovaries who were treated in the Obstetric and Gynecologic Hospital of the University of Tours. In our hospital, no lymphadenectomies for such epithelial ovarian carcinoma patients are carried out. We studied the survival of these patients that were operated upon from 1 December 1975 until 1 August 1997. 43 epithelial ovarian carcinoma patients were studied; 22 were stage Ia, 1 was stage Ib and 20 were stage Ic. The average age was 58 years (range 27-86 years). 5% (2/43) developed recurrent disease and the rates of disease-free and overall survival after 5 years were 83% and 90.3% respectively. These results are very close to those described in literature for patients who underwent paraaortic and pelvic lymphadenectomy. As no series to date has demonstrated the benefit of paraaortic lymphadenectomy on survival and we know that paraaortic lymphadenectomy increases morbidity, we think it reasonable to propose surgery without lymphadenectomy for the treatment of early ovarian epithelial cancer patients whose disease is apparently confined to the ovaries.

Association between breast cancer and family malignancies.

In a case-control study, the relationship between a family history of cancer of the breast, ovary, colon, uterus or prostate and the risk of breast cancer was investigated. The data consisted of family histories from 495 breast cancer cases and 785 controls aged 20-56 years. A positive association was found between the occurrence of breast cancer and a history of breast cancer in the families of the subjects affected. This relationship increased linearly with both the degree of kinship of the affected relatives and with their number. The risk of breast cancer associated with other types of cancer in the family was not significantly different from unity.

Radical hysterectomy for stage I and II endometrial carcinoma: a retrospective analysis of 179 cases.

Total hysterectomy with bilateral salpingo oophorectomy is the traditional treatment for endometrial carcinoma. In an effort to improve local control rates, we have surgically treated our Stage I and II patients with radical hysterectomy and pelvic lymphadenectomy (RH-PL). Between 1976 and 1987 we have treated 179 patients with endometrial adenocarcinoma (125 Stage I and 54 Stage II) with the following modalities. Uterovaginal brachytherapy (60 Gy) was performed first and then 6 weeks later an RH-PL was performed. Twenty-nine patients received external pelvic irradiation (45 Gy) because of tumor invasion beyond the internal two-thirds of the myometrium and/or lymph node involvement. The local control rate was 87% (92% for Stage I, 76% for Stage II). Distant metastases occurred in 24 patients (13%). Five-year actuarial survival rates were 80% for Stage I and 61% for Stage II patients. Prognostic factors were nodal status, histological grading, depth of tumor myometrial invasion, histologic status of the hysterectomy specimen, and peritoneal cytology. Late severe complications occurred for 13 patients (7%). These results are comparable to those published for patients treated with less extensive surgery. We conclude that such an extensive surgery (especially pelvic lymphadenectomy) appears to be useless for all patients with bad prognostic factors requiring pelvic external irradiation. We only still perform external iliac node samples for patients with Stage I grade 1 tumors without deep tumor invasion into the myometrium.

Prognostic significance of breast relapse after conservative treatment in node-negative early breast cancer.

The prognostic significance of local relapse after conservative treatment of early stage breast carcinoma has been controversial. To determine the incidence and the prognostic value of a breast relapse, we analyzed the results obtained in a series of patients with pT1pN0 presentation of breast carcinoma treated conservatively without adjuvant medical treatment. From 1976 to 1986, 202 patients with invasive breast carcinoma of less than 2 cm without lymph node involvement were treated with surgery and radiation therapy. The overall survival rate was 97.2% at 5 years. Locoregional relapses occurred in 16 patients (7.9%). In these patients, the overall survival rate was significantly decreased as compared to that of patients without local relapse (87.5% versus 98.3% at 5 years, p less than 0.001). The probability of remaining metastasis-free was also significantly decreased (80.2% vs 91.3%, p less than 0.001). Most relapses (94%) appeared at or close to the primary site. Salvage local treatment was possible in 14/16 patients (87.5%). Age, menopausal status, size and site of primary tumor, histological grade, and boost technique did not influence significantly the risk of local relapse occurrence. We concluded that the occurrence of a breast relapse after a successful local conservative treatment is a pejorative prognostic factor predictive of a high risk of distant metastasis development. There is a need to individualize factors that could allow discrimination of patients with a high probability of local relapse and subsequent metastasis.

Primary chemotherapy and radiosurgical breast-conserving treatment for patients with locally advanced operable breast cancers.

PURPOSE: The traditional surgical treatment for operable breast cancer larger than 3 cm is mastectomy. In order to avoid mutilating surgery, we administered primary chemotherapy to 80 patients with operable non metastatic large breast cancer T2 > 3 cm and T3, N0-N1. The purpose of the study was to evaluate the breast-conserving rate induced by this treatment strategy and determine if it is a safe alternative for women with locally advanced breast carcinomas that are responders to an induction chemotherapy. METHODS AND MATERIALS: The mean age was 50.1 years. Forty-three patients were T2 > 3 cm, 37 were T3. Twenty-six were N0 and 54 were N1. Mean tumor size was 5.4 cm. Patients were treated with three courses of the MVCF regimen (Mitoxantrone, Vindesin, Cyclophosphamide, and 5 Fluorouracil) every 4 weeks and then with a radiosurgical combination. RESULTS: The overall response rate to induction chemotherapy was 51% with 17.5% complete tumor regression. Twenty-one percent of the patients developed grade 3 or 4 chemotherapy toxic effects, all acceptable and reversible. Breast-conserving treatment was feasible in 42.5% (34/80). Twenty patients (25%) were treated with a radiosurgical combination (tumorectomy+radiation therapy), 14 (17.5%) with radiotherapy alone (external irradiation and brachytherapy). Age, tumor stage, histology, hormonal status, hormonal receptors rate had no influence on the frequency of the observed regressions. Isolated recurrences occurred in five patients, two conservatively treated and three treated with mastectomy. Metastatic relapses were observed in 20 patients (12% in the responders and 38.5% in the non responders to chemotherapy) (p < 0.02). Five-year actuarial survival was 73% and was significantly better for responders to the induction treatment. CONCLUSION: These results suggest that primary chemotherapy and radiosurgical breast conserving treatment is a safe alternative to mastectomy for patients with locally advanced operable breast cancer. The long-term benefit of this strategy must be evaluated in well designed controlled trials.

Preoperative or postoperative brachytherapy for patients with endometrial carcinoma stage I and II.

In endometrial carcinoma, vaginal vault brachytherapy is performed to improve the local control rate and to decrease vaginal recurrences. To assess the best chronology of this brachytherapy compared to surgery, we have retrospectively analyzed results of treatment of patients treated either with preoperative brachytherapy (60 Gy) and then radical hysterectomy with bilateral salpingo oophorectomy (RH-BSO) (Group 1), or with RH-BSO and then postoperative brachytherapy (60 Gy) (Group 2). There were one hundred twenty-one patients in Group 1 and 63 in Group 2. The mean age was 61.8 years in Group 1 and 64.3 in Group 2. In Group 1, 73% of the patients were Stage I, and 77.6% were in Group 2. The two groups were comparable for histological grading and depth of tumoral invasion into the myometrium. Brachytherapy was delivered with one uterine and two vaginal sources in Group 1 and with three vaginal sources in Group 2. Doses to the reference volume and to reference points were calculated according to ICRU recommendations. Brachytherapy data were similar in the two groups except reference volume, which was smaller in Group 2. Local control rate was 87% in Group 1 and 91% in Group 2. Distant metastasis occurred in 12% of patients in Group 1 and 9% in Group 2. The 5-year actuarial survival rate was 84% in Group 1 and 89% in Group 2. Regarding stage, histological grading, and depth of tumoral invasion, no differences were observed between the two therapeutic groups. The only prognostic factor in the entire population was Stage. The 5-year actuarial survival rate was 91% for Stage I patients and 69% for Stage II (p value less than 0.03). The late severe complication rate was 14% in Group 1 and 7.9% in Group 2, a difference which was not statistically significant. We concluded that since no differences were observed between the two techniques, vaginal brachytherapy should be performed postoperatively when surgery is the first treatment (Stage I or II, grade 1 or 2, and no deep tumoral invasion into the myometrium).

Disappearance of the in situ component: a criterion predictive of metastasis in breast cancer after local relapse.

Local recurrence after conservative treatment of breast cancer is associated with a significant risk for metastasis. In order to identify criteria predictive of metastasis in this subset of women, we analyzed a series of 35 patients with local relapse among 512 consecutive patients treated with tumorectomy and radiotherapy. When relapse occurred within 2 years of initial treatment, overall 2-year survival from the time of local relapse was 39.5%. When local relapse occurred more than 2 years from initial therapy, 2-year survival was 80.5% (p < 0.001). Pathological slides of both initial and recurrent tumors were reviewed and compared. In 17 patients, local relapse and initial tumor had the same morphological features, with an in-situ component either absent or present in the same proportion. Metastasis occurred in two of these patients. In contrast, 9 of 12 patients in whom the proportion of non-invasive carcinoma had decreased at the time of local recurrence developed metastasis. Overall 2-year survival from the time of relapse was significantly better in the former group of patients (93.3% versus 52.5%, p < 0.05). We concluded that early relapses have a poor prognostic significance and that disappearance of the in-situ component or increase of the invasive component at the time of relapse is a feature predictive of tumor-related death and that more intensive therapy might benefit to this subset of women.

Reproductive factors and breast cancer risk. Effect of age at diagnosis.

The data from a French case-control study of 495 patients with breast cancer and 542 control subjects interviewed in five French public hospitals, were analyzed to assess the effect of reproductive factors (age at menarche, age at first full-term pregnancy, the time interval between these two ages, and parity) on the risk of breast cancer. Age at menarche, age at first full-term pregnancy, the time interval between these two ages, and parity appeared to have a limited influence on breast cancer risk. However, the relationship between these factors and the risk of breast cancer varied according to the age at breast cancer diagnosis. In the youngest group of women, the most consistent effects came from factors occurring early in life (menarche, first full-term pregnancy, and consequently the time interval between these two events). These factors had a null or weak effect on the oldest group of women. The protective effect of high parity was confined to the oldest group of women.

Argyrophilic cells in mammary carcinoma.

Breast tumor tissues were treated by the Grimelius procedure and examined for the presence of argyrophilic cells. Carcinomas found to contain argyrophilic cells did not include classic carcinoid tumors; the group was, in fact, heterogeneous, comprising poorly differentiated ductal carcinomas, lobular carcinomas, carcinomas of uncertain origin, and colloid carcinomas. Colloid tumors were the most frequently encountered. The prominence of argyrophilic cells in colloid carcinomas raises the possibility that development into mucin-producing cells is propitious for endocrine differentiation.

Variations in the risk of breast cancer associated with a family history of breast cancer according to age at onset and reproductive factors.

In a case-control study of 495 breast cancer patients and 785 controls between 20 and 56 years of age, the risk of breast cancer associated with a family history of breast cancer was studied according to age and reproductive factors. The familial risk of breast cancer was not significantly modified by age at onset, age at menarche, number of children, age at first full-term pregnancy, menstrual cycle length or age at menopause. However, the familial risk significantly increased with the number of abortions (p < 0.05) and seemed to decrease after a natural menopause (p = 0.08). These results suggest that a familial predisposition to breast cancer exerts the same influence during the first six decades of life, except maybe when there are isolated or repeated events such as abortions or artificially imposed menopause, in which case the risk is apparently greater.

Oral contraceptives and breast cancer: a French case-control study.

The relationship between the risk of breast cancer and oral contraceptive use was investigated in a case-control study conducted in France between 1983 and 1987 in five public hospitals. Some 464 cases aged 25 to 56 years and 542 matched controls were interviewed about their history of the use of oral contraceptives (OC). Results are given for the entire population and for the subgroup of 358 and 379 premenopausal cases and controls. The multivariate relative risk estimate, for ever user, was 1.5 (p less than 0.01) in the whole group as well as in the premenopausal subgroup (p less than 0.02). However, there was no evidence that the effect varied appreciably according to duration of use, age at first use, use before first full-term pregnancy (FFTP) and time since first or last use. The risk was not altered for any particular brand of OC. We conclude that, because of the widespread attention given to the relationship between OC use and breast cancer, information bias might be responsible for part of the excess in risk observed among OC ever users.

PIP: The relationship between the risk of breast cancer and oral contraceptive (OC) use was investigated in a case-control study conducted in France between 1983-87 in 5 public hospitals. Some 464 cases ages 25-56 years and 542 matched controls were interviewed about their history of OC use. Results are provided for the entire population and for the subgroups of 358 and 379 premenopausal cases and controls. The multivariate relative risk estimate, for ever-use, was 1.5 (p0.01) in the entire group as well as in the premenopausal subgroup (p0.02). However, there was no evidence that the effect varied appreciably according to the duration of use, age at 1st use, use prior to 1st fullterm pregnancy, and time since 1st or last use. The risk was not altered for any particular OC brand. The authors conclude that because of the widespread attention given to the relationship between OC use and breast cancer, information bias might be responsible for a part of the excess of risk observed among OC ever-users.

Cell abnormalities associated with human papillomavirus-induced squamous intraepithelial cervical lesions. Multivariate data analysis.

One hundred ninety-six cervical scrapings were obtained for simultaneous research of cell abnormalities in Papanicolaou smears and detection of genital human papillomavirus (HPV) genotypes by polymerase chain reaction in extracted DNA from each clinical sample. The samples described by six discriminant cytologic parameters, and a synthetic HPV-presence/absence parameter provided an efficient matrix for multiple correspondence analysis. This statistical analysis displayed a plurality of HPV-related cell abnormalities in squamous intraepithelial lesions, and a high correspondence between HPV infection and the presence of multinucleated squamous cells, morphologically transformed keratinocytes (dyskaryotic cells), koilocytes, and cellular changes related to epithelial maturation. Because of the low proportion of detectable koilocytes in the HPV-infected scrapings, the authors also inferred that cellular changes related to epithelial maturation and morphologically transformed keratinocytes are the most accurate and efficient cell abnormalities, in terms of frequency and correlation, for cytodiagnosis of HPV-induced or associated squamous intraepithelial cervical lesions.