Key words: GLUT-1; positron emission tomography; [F-18]-fluorodeoxyglucose; standardized uptake value; ovarian cancer; biomarkerOvarian cancer is locally aggressive and often disseminates to distant sites. 1 For all stages, the 5-year survival rate is only 46%. 2 Treatment planning depends on information regarding the presence or absence of metastases, the local situation and the malignant activity of the primary tumor. In general, anatomic imaging has been the fundamental approach to cancer imaging, and its daily use has been supported in the management of individual patients with cancer. In ovarian cancer, chest and abdomen CT is used to screen for metastases and MRI is used to assess the local situation.However, anatomic imaging methods for cancer management are of limited value, due to the difficulty in predicting whether the tumor will respond to chemotherapy in patients with ovarian cancer. Treatment other than primary debulking surgery for cancer of the ovary has been proposed as patients with bulky, nonresectable disease do not benefit from primary surgery. 3,4 Analysis of therapeutic outcome in patients with advanced cancer of the pancreas and esophagus provides clear evidence that neoadjuvant chemotherapy before surgery enables downstaging, thereby improving the operability as well as the prognosis of patients. 5,6 In an advanced ovarian cancer study, Kuhn et al. 7 reported that neoadjuvant chemotherapy apparently improved patient prognoses. Thus, early detection of tumor response to chemotherapy would be useful in determining whether such an approach is suitable for ovarian cancer patients.For assessment of malignant activity (which is a biomarker of response to chemotherapy, prognosis and overall chance of survival in ovarian cancer patients), measurement of viability and grading of tumors, 8 -10 cell proliferation 11-13 and glucose metabolism 14,15 are instructive. However, these assessments are performed using tissue specimens, requiring laparotomy for a biopsy or resection of ovarian tissue, which is subject to tissue sampling errors. A noninvasive in vivo imaging technique to assess malignant activity and gain prognostic information of ovarian tumors may be more accurate, as well as provide a more acceptable alternative for patients initially reluctant submit to minor surgery.FDG-PET is a unique, noninvasive method for studying biochemical and metabolic changes in cancer tissue. 16 FDG uptake has been correlated with tumor proliferation rate, tumor grade and expression of glucose transporters, which are biomarkers of the response to chemotherapy and the prognosis and overall chances of survival in cases of malignant disease. 16 -20 Our aim was to determine whether FDG-PET is useful for the assessment of malignant activity and the gathering of prognostic information in ovarian cancer. We compared FDG uptake, quantified as an SUV, with clinical stage; tumor grade of cells, assessed by HE staining; and cell proliferation and glucose metabolism, assessed by immunohistochemistry (MIB-1 LI and inten...

Objective To determine the feasibility and safety of transverse fundal incision with manual placental removal in women with placenta praevia and possible placenta accreta. Design Case series. Setting Four level‐three Japanese obstetric centres. Population Thirty‐four women with prior caesarean section and placenta praevia that widely covers the anterior uterine wall, in whom placenta accreta cannot be ruled out. Methods A transverse fundal incision was performed at the time of caesarean section and manual placental removal was attempted under direct observation. Main outcome measure Operative fluid loss. Results The total volume of fluid lost during our operative procedure compares favourably with the volume lost during our routine transverse lower‐segment caesarean sections performed in patients without placenta praevia or accreta. The average fluid loss was 1370 g. No patients required transfer to intensive care, and there were no cases of fetal anaemia. Conclusions This procedure has the potential to reduce the heavy bleeding that arises from caesarean deliveries in women with placenta praevia and placenta accreta.

The grade of histologic differentiation is one of the most important prognostic factors in patients with endometrial carcinoma and postoperative staging. The aim of this study was to investigate whether 16a-18 F-fluoro-17b-estradiol ( 18 F-FES) and 18 F-FDG PET reflect clinicopathologic features in patients with endometrial tumors. Methods: A total of 22 patients with endometrial adenocarcinoma and 9 with endometrial hyperplasia (mean age, 56.0 6 15.3 y) underwent 18 F-FES PET for estrogen receptor imaging and 18 F-FDG PET. Regional values of tracer uptake were evaluated using standardized uptake value (SUV) and the SUV ratio of 18 F-FDG to 18 F-FES. The accuracy for predicting tumor aggressiveness defined as high-risk carcinoma (International Federation of Gynecology and Obstetrics [FIGO] stage $ Ic or histologic grade $ 2), low-risk carcinoma (FIGO stage # Ib and grade 1), and hyperplasia was compared for each PET parameter using receiver-operating-characteristic (ROC) analysis. The diagnostic accuracy of MRI findings for clinical staging was also compared. Results: Although the SUV for 18 F-FDG was significantly lower in endometrial hyperplasia than in carcinoma, a significant difference between high-risk and low-risk carcinoma was observed only in SUV for 18 F-FES. High-risk carcinoma showed a significantly greater 18 F-FDG-to-18 F-FES ratio (3.6 6 2.1) than did low-risk carcinoma (1.3 6 0.5, P , 0.01) and hyperplasia (0.3 6 0.1, P , 0.005). Low-risk carcinoma showed a significantly higher 18 F-FDG-to-18 F-FES ratio than hyperplasia (P , 0.0001). In ROC analysis, the most accurate diagnostic PET parameter for predicting high-risk and low-risk carcinoma was the 18 F-FDG-to-18 F-FES ratio. The optimal 18 F-FDG/ 18 F-FES cutoff value of 2.0, determined by ROC analysis, revealed 73% sensitivity, 100% specificity, and 86% accuracy, which was better than the 77% accuracy for MRI. The 18 F-FDGto-18 F-FES ratio of 0.5 yielded a correct diagnosis for carcinoma from hyperplasia with 100% accuracy. Conclusion: Endometrial carcinoma reduces estrogen dependency with accelerated glucose metabolism as it progresses to a higher stage or grade. 18 F-FES and 18 F-FDG PET studies provide a new index of the 18 F-FDG-to-18 F-FES ratio, which is considered the most informative index reflecting tumor aggressiveness. This index will be useful for making noninvasive diagnoses and deciding the appropriate therapeutic strategy for patients with endometrial carcinoma.

The addition of FDG PET to CT increases accuracy in staging of ovarian cancer.

Chemoresistance enables cancer cells to evade apoptotic stimuli and leads to poor clinical prognosis. It arises from dysregulation of signaling factors responsible for inducing cell proliferation and death and for modulating the microenvironment. In gynecologic cancers, p53 is a pivotal determinant of cisplatin sensitivity, while BCL-2 family members are associated with taxane sensitivity. Mitochondria fusion and fission dynamics are required for many mitochondrial functions and are also involved in mitochondria-mediated apoptosis, which is closely associated with chemosensitivity. Mitochondrial dynamics are controlled by a number of intracellular proteins, including fusion (Opa1 and mitofusion 1 and 2) and fission proteins (Drp1 and Fis1), which can be proapoptotic or antiapoptotic, depending on the cell types, status, and stimuli from the microenvironment. This paper describes the role of mitochondrial dynamics in the mechanism of chemoresistance and the evidence supporting a significant contribution of a hyperfusion state to chemoresistance in gynecological cancers. Moreover, we discuss our findings showing that enforced fission induces apoptosis of cancer cells and sensitizes them to chemotherapeutic agents. Understanding the regulation of mitochondrial dynamics in chemoresistance may provide insight into new biomarkers that better predict cancer chemosensitivity and may aid the development of effective therapeutic strategies for clinical management of gynecologic cancers.

Canine distemper of domestic dogs is caused by canine distemper virus (CDV), a member of the morbilliviruses. It has been a highly contagious disease of great veterinary importance for centuries, but for the last several decades it has been controlled satisfactorily by modified live vaccines. In the 1990s, however, it was described that CDV strains genetically different from vaccine strains may have caused the disease in vaccinated dogs. The highest antigenic variation is found in the H protein. Therefore, in the present study, hemagglutinin (H) genes obtained from current vaccines and field isolates and amplified directly from clinical specimens were genetically analyzed by restriction fragment length polymorphism assay and sequencing. Phylogenetic analysis of the H-gene amino acid sequences revealed that at least two CDV genotypes are circulating among dogs in Japan; one is a genotype to which almost all Japanese CDV isolates belong and the other has not been previously described. Both are separate and independent from the other lineages or genotypes of vaccine strains, as well as European and U.S. CDV isolates. The results suggest that CDV has also evolved in Japan, and further studies will be needed for an evaluation and possible improvement of the efficacies of current CDV vaccines.

Formation of a theca cell (TC) layer is an important physiologic event that occurs during early follicular development. Nevertheless, little is known concerning the nature and regulation of the formation of the TC layer during follicular growth. Using an established coculture system in this study, we examined the hypothesis that stromal cells differentiate into TCs during early follicular development and that this process involves interaction with granulosa cells (GCs). Ovarian stromal cells from the bovine ovarian cortex (S(C)) and medulla (S(M)) were cultured with or without GCs from small antral follicles. The presence of GCs increased the number of lipid droplets and mitochondria, and it stimulated androstenedione production in S(C) and S(M). However, luteinizing hormone/choriogonadotropin receptor (LHCGR) mRNA abundance and hCG-induced cAMP and androstenedione production were increased in S(C) but not in S(M) by the presence of GCs. The present results indicate that GCs are involved in the functional differentiation and the acquisition of LH responsiveness in stromal cells of the ovarian cortex. We suggest that GC-S(C) interaction is important in the formation of the TC layer during early follicular development, although the nature of this interaction remains to be determined.

ER expression and glucose metabolism of uterine tumors measured by using PET showed opposite tendencies. PET studies with both FES and FDG could provide pathophysiologic information for the differential diagnosis of uterine tumors.