Health facility-based Active Management of the Third Stage of Labor: findings from a national survey in Tanzania

Hemorrhage is the leading cause of obstetric mortality. Studies show that Active Management of Third Stage of Labor (AMTSL) reduces Post Partum Hemorrhage (PPH). This study describes the practice of AMTSL and barriers to its effective use in Tanzania. A nationally-representative sample of 251 facility-based vaginal deliveries was observed for the AMTSL practice. Standard Treatment Guidelines (STG), the Essential Drug List and medical and midwifery school curricula were reviewed. Drug availability and storage conditions were reviewed at the central pharmaceutical storage site and pharmacies in the selected facilities. Interviews were conducted with hospital directors, pharmacists and 106 health care providers in 29 hospitals visited. Data were collected between November 10 and December 15, 2005. Correct practice of AMTSL according to the ICM/FIGO definition was observed in 7% of 251 deliveries. When the definition of AMTSL was relaxed to allow administration of the uterotonic drug within three minutes of fetus delivery, the proportion of AMTSL use increased to 17%. The most significant factor contributing to the low rate of AMTSL use was provision of the uterotonic drug after delivery of the placenta. The study also observed potentially-harmful practices in approximately 1/3 of deliveries. Only 9% out of 106 health care providers made correct statements regarding the all three components of AMTSL. The national formulary recommends ergometrine (0.5 mg/IM) or oxytocin (5 IU/IM) on delivery of the anterior shoulder or immediately after the baby is delivered. Most of facilities had satisfactory stores of drugs and supplies. Uterotonic drugs were stored at room temperature in 28% of the facilities. The knowledge and practice of AMTSL is very low and STGs are not updated on correct AMTSL practice. The drugs for AMTSL are available and stored at the right conditions in nearly all facilities. All providers used ergometrine for AMTSL instead of oxytocin as recommended by ICM/FIGO. The study also observed harmful practices during delivery. These findings indicate that there is a need for updating the STGs, curricula and training of health providers on AMTSL and monitoring its practice

Identification of genes and pathways associated with cytotoxic T lymphocyte infiltration of serous ovarian cancer

BACKGROUND: Tumour-infiltrating lymphocytes (TILs) are predictors of disease-specific survival (DSS) in ovarian cancer. It is largely unknown what factors contribute to lymphocyte recruitment. Our aim was to evaluate genes and pathways contributing to infiltration of cytotoxic T lymphocytes (CTLs) in advanced-stage serous ovarian cancer. METHODS: For this study global gene expression was compared between low TIL (n=25) and high TIL tumours (n=24). The differences in gene expression were evaluated using parametric T-testing. Selectively enriched biological pathways were identified with gene set enrichment analysis. Prognostic influence was validated in 157 late-stage serous ovarian cancer patients. Using immunohistochemistry, association of selected genes from identified pathways with CTL was validated. RESULTS: The presence of CTL was associated with 320 genes and 23 pathways (P<0.05). In addition, 54 genes and 8 pathways were also associated with DSS in our validation cohort. Immunohistochemical evaluation showed strong correlations between MHC class I and II membrane expression, parts of the antigen processing and presentation pathway, and CTL recruitment. CONCLUSION: Gene expression profiling and pathway analyses are valuable tools to obtain more understanding of tumour characteristics influencing lymphocyte recruitment in advanced-stage serous ovarian cancer. Identified genes and pathways need to be further investigated for suitability as therapeutic targets

The ErbB signalling pathway: protein expression and prognostic value in epithelial ovarian cancer

Ovarian cancer is the most frequent cause of death from gynaecological cancer in the Western world. Current prognostic factors do not allow reliable prediction of response to chemotherapy and survival for individual ovarian cancer patients. Epidermal growth factor receptor (EGFR) and HER-2/neu are frequently expressed in ovarian cancer but their prognostic value remains unclear. In this study, we investigated the expression and prognostic value of EGFR, EGFR variant III (EGFRvIII), HER-2/neu and important downstream signalling components in a large series of epithelial ovarian cancer patients. Immunohistochemical staining of EGFR, pEGFR, EGFRvIII, Her-2/neu, PTEN (phosphatase and tensin homologue deleted on chromosome 10), total and phosphorylated AKT (pAKT) and phosphorylated ERK (pERK) was performed in 232 primary tumours using the tissue microarray platform and related to clinicopathological characteristics and survival. In addition, EGFRvIII expression was determined in 45 tumours by RT–PCR. Our results show that negative PTEN immunostaining was associated with stage I/II disease (P=0.006), non-serous tumour type (P=0.042) and in multivariate analysis with a longer progression-free survival (P=0.015). Negative PTEN staining also predicted improved progression-free survival in patients with grade III or undifferentiated serous carcinomas (P=0.011). Positive pAKT staining was associated with advanced-stage disease (P=0.006). Other proteins were expressed only at low levels, and were not associated with any clinicopathological parameter or survival. None of the tumours were positive for EGFRvIII. In conclusion, our results indicate that tumours showing negative PTEN staining could represent a subgroup of ovarian carcinomas with a relatively favourable prognosis