Prognostic value of a proliferation index including MIB1 and argyrophilic nucleolar organizer regions proteins in node-negative breast cancer.

OBJECTIVE: This study was designed to evaluate a cell proliferation marker, including the percentage of cycling cells (MIB1), and the duration of the cell cycle (assessed by argyrophilic nucleolar organizer regions proteins [AgNORs] measurement). STUDY DESIGN: We included 90 patients with invasive node-negative breast cancer. None received chemotherapy. With the help of a double-staining technique, a proliferation index (PI) was determined by multiplying the percentage of MIB1-positive cells by the mean area of the AgNORs present in those MIB1-positive cells. PI was evaluated for its impact on overall survival (OS) and disease-free survival (DFS). RESULTS: We demonstrated that PI was correlated to OS. For DFS, it conserved its high prognostic value only in univariate analysis. The global amount of AgNORs was more discriminative for DFS. CONCLUSION: PI and AgNOR quantification supplied additional prognosis information in node-negative patients, and we propose to integrate them in further studies.

Fluorescence in situ hybridization and immunohistochemical analysis of p53 expression in endometrial cancer: prognostic value and relation to ploidy.

BACKGROUND: Endometrial carcinoma is the most common gynecological malignancy. Several molecular biological characteristics have been studied for their potential value in patient management. OBJECTIVES: Our objectives were to compare p53 immunohistochemical expression with P53 gene status determined by fluorescence in situ hybridization (FISH) and to compare these characteristics with ploidy and with classical clinical and histological prognostic factors. MATERIALS AND METHODS: We reviewed stored specimens from 43 patients with endometrial cancer diagnosed in 1999-2004. P53 FISH and immunohistochemistry were performed, together with imaging cytometry to calculate DNA ploidy. RESULTS: Thirteen of the 43 endometrial carcinomas (30.2%) showed P53 loss of heterozygosity (LOH). P53 LOH correlated with the histological type (P = .03) and the histological grade (P = .004). Quantitative immunohistochemical expression of p53 protein correlated with the histological type (P = .0001). With a cutoff of 10% of p53-positive cells, p53 overexpression correlated with the histological type (P = .003) and grade (P = .0008). No relation was found between P53 LOH or immunohistochemical expression and the disease stage, the depth of myometrial invasion, lymph node status, lymphovascular space involvement, recurrence, or death from cancer. Nondiploid carcinomas showed deeper myometrial invasion than diploid carcinomas (P = .01). No relation was observed between ploidy and qualitative or semiquantitative p53 expression or P53 LOH. CONCLUSION: In endometrial cancer, FISH analysis of P53 status adds no significant prognostic information compared with immunohistochemical p53 analysis.

Characteristics and outcome of fetal cystic hygroma diagnosed in the first trimester.

OBJECTIVE: The aim of this study was to determine the course of pregnancy and the neonatal outcome of fetuses with cystic hygroma diagnosed at 10-14 weeks' gestation. METHODS: Maternal and fetal data (nuchal translucency, karyotype, pregnancy outcome) in cases of fetal cystic hygroma, admitted or referred to our antenatal diagnostic centre, were prospectively entered into a computer database. Paediatric outcome was analysed when relevant. RESULTS: Some 72 fetuses had cystic hygroma. The mean size of the cystic hygroma was 7.9 mm. Chromosomal abnormalities were present in 52.7% of cases (38/72), including 14 cases (36.8%) of Down syndrome. A total of 34 chromosomally normal pregnancies gave rise to 18 live births (52.9%), with no visible serious structural abnormalities. The outcome of pregnancy was unfavourable (miscarriage, elective termination, serious structural abnormalities) in 77.7% of cases (56/72). The 18 live-born infants were followed up for 17-98 months. Sixteen infants developed normally, while 1 developed Noonan's syndrome and 1 had a urinary tract abnormality (pyelo-ureteral junction; PUJ). CONCLUSION: These data suggest that the prognosis of fetal cystic hygroma detected during the first trimester is poor, and show that sonographic evaluation of fetal nuchal translucency thickness in the first trimester is crucial.

Cavaterm thermal balloon endometrial ablation versus hysteroscopic endometrial resection to treat menorrhagia: the French, multicenter, randomized study.

STUDY OBJECTIVE: To compare the efficacy and safety of Cavaterm thermal balloon endometrial ablation with hysteroscopic endometrial resection. DESIGN: Multicenter randomized trial (Canadian Task Force classification I). SETTING: Departments of obstetrics and gynecology in French university hospitals. PATIENTS: Fifty-one women with menorrhagia unresponsive to medical treatment. INTERVENTIONS: Women were randomized to thermal destruction of the endometrium or to hysteroscopic endometrial resection. Women completed preoperative, 6-, and 12-month postoperative pictorial charts to determine Higham blood loss scores and a satisfaction questionnaire. Operative time, discharge time, complication rate, and resumption of normal activities were evaluated for each group. MEASUREMENTS AND MAIN RESULTS: Amenorrhea rates were 36% (95% CI 19%-56%) and 29% (95% CI 8%-51%) in the Cavaterm and the endometrial resection groups at 12 months, respectively (ns). Both treatments significantly reduced uterine bleeding. The median decrease in Higham score at 12 months was significantly higher in women treated by Cavaterm (377, range 108-1300) than in women treated by resection (255, range -82 to 555) (p=.006). A subsequent hysterectomy for recurrent bleeding was performed in 2 women, both previously treated by resection. The rate of women reporting good or excellent satisfaction was 89% (95% CI 72%-98%) in the Cavaterm group and 79% (95% CI 54%-94%) in the resection group at 12 months. Discharge time was significantly lower in women treated by Cavaterm, although postoperative pain at 1 hour was higher. There were no major complications in either group. CONCLUSIONS: Cavaterm thermal balloon ablation was as effective as hysteroscopic endometrial resection to treat menorrhagia, both resulting in a significant reduction in menstrual blood loss and high patient satisfaction.

Conservative treatment of ectopic pregnancy in a cesarean scar.

BACKGROUND: Pregnancy developing in a cesarean scar is a very rare but possibly life-threatening condition because of the risk of rupture and excessive hemorrhage. CASE: A 34-year-old woman presented with lower abdominal pain at 6 weeks of gestation. A cesarean delivery had been performed 3 years earlier. Transvaginal ultrasound examination revealed a viable pregnancy developing in the anterior wall of the uterus. The patient was treated successfully with systemic methotrexate and curettage. CONCLUSION: Conservative management with methotrexate and curettage can be considered in the treatment of ectopic cesarean scar pregnancy.

Recurrent human papillomavirus infection detected with the hybrid capture II assay selects women with normal cervical smears at risk for developing high grade cervical lesions: a longitudinal study of 3,091 women.

To test the reliability of the Hybrid Capture II (HC-II) assay detecting 13 high-risk human papillomavirus (HR-HPV) types for the screening of cervical lesions, we monitored by cytology, HR-HPV testing, colposcopy and biopsy, 3,091 women with normal smears at the first entry. Our primary endpoint was clinical progression defined as the presence of a high-grade lesion (HGSIL) at the biopsy. In our population of 659 HR-HPV-infected women, 241 (36.6%) had a positive HR-HPV test at 2 to 4 examinations with a final histological diagnosis of HGSIL in 51 cases (21.2%) within 4 to 36 months, while women with regressive HPV infection did not develop any lesion during the same period. In the cohort of 2,432 women testing negative for HR-HPV infection, only 2 women (0.08%) developed a HGSIL. Both were HR-HPV positive 18 and 24 months after the first entry, at the time of diagnosis of disease. The RR of incident HGSIL when a HR-HPV was detected at enrollment in women with normal smears was 96.7 (95% CI, 95.8-97.7). The RR increased to 237.3 (95% CI, 222.8-251.8) when the HR-HPV test remained positive at 2 controls, and to 314.3 (95% CI, 260.7-367.9) when the HR-HPV test was positive at 3 controls. The evaluation of the viral load of HR-HPV by the HC-II did not represent a sensitive approach to predict the recurrence of HR-HPV infection and/or the apparition of HGSIL. Nevertheless, a recurrent HR-HPV infection detected with HC-II represents a reliable tool to select populations at risk for the development of HGSIL.

Usefulness of DNA ploidy measurement on liquid-based smears showing conflicting results between cytology and high-risk human papillomavirus typing.

To improve the positive predictive value (PPV) for high-risk human papillomavirus (HR-HPV) in primary screening, DNA ploidy was measured on the same liquid-based sample by image cytometry in 984 cases showing discrepancies between cytology and HR-HPV testing. Of the conflicting results, 14.5% corresponded to a cytologic lesion (from atypical squamous cells of undetermined significance to high-grade squamous intraepithelial lesion [HSIL]) without HPV detected, and 85.5% of smears were within normal limits but revealed an HR-HPV infection. A suspect DNA profile was associated significantly with a lesion. In 497 patients who underwent repeated HPV testing, a normal DNA profile at the first smear predicted the clearance of HPV infection (sensitivity, 81.5%; specificity, 45.4%; PPV, 69%; negative predictive value, 62.4%). In persistent HR-HPV infection, a suspect DNA profile at the first smear increased the PPVfrom 10.8% to 22.7% for the detection of a histologically proven HSIL with a sensitivity of 95.2%. DNA ploidy can be used to select smears with high risk of HSIL, especially in cases of persistent HR-HPV infection.