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Sorafenib is an oral multikinase inhibitor targeting Raf and other kinases. The anti-tumor effect of sorafenib is thought to be mediated through its inhibition of the RAS-Raf-Erk pathway, as well as its inhibition of VEGFR and PDGFR. Sorafenib has been effective at treating patients with renal cell carcinoma (RCC). Ovarian clear cell carcinoma (OCCC) is a chemoresistant subtype of ovarian cancer. OCCC is represented by cells with clear cytoplasm that resemble those observed in RCC. Using a microarray database, the gene expression profile of OCCC was similar to that of RCC. The effects of sorafenib against human OCCC are unknown. Therefore, we used sorafenib to treat two patients with recurrent chemoresistant OCCC, and observed good effect in both of them without severe side effects. We believe that sorafenib is an effective agent against OCCC. Given the chemoresistant nature of this tumor, this drug appears to be very valuable.

[Objectives]The sensitivity of the current 10 mm cut-off diameter that is used to diagnose lymph node (LN) metastasis is too low. This is the first study to develop a new criterion to diagnose LN metastasis in a region-by-region manner using multi-detector computed tomography (MDCT). [Methods]1) The short-axis diameter of the LNs in MDCT images from 1-mm slices obtained immediately prior to surgery was compared with the pathological diagnosis in 78 uterine cervical cancer patients undergoing primary surgery. For the region-by-region analysis, we divided para-aortic and pelvic spaces into 13 regions. 2) In 28 cases in which patients received neoadjuvant chemotherapy (NAC) followed by surgery, we compared MDCT images before and after NAC. [Results]1) The optimal cut-off in the region-by-region analysis was 5 mm, yielding 71% sensitivity and 79% specificity. 2) NAC significantly decreased LN size (p < 0.0001). NAC decreased the number of swollen LN regions (> 5 mm) from 51% (81/158) to 26% (41/158). [Conclusions]The new criterion developed using MDCT could be effective for accurately assessing LN status. It also facilitates the assessment of NAC efficacy regarding the eradication of LN metastases.

An increasing number of women with severe endometriosis have conceived through assisted reproductive technology, but endometriosis can cause life-threatening complications for both the mother and baby during pregnancy. We describe a case of endometriosis-induced spontaneous ileal perforation in pregnancy with massive intestinal haemorrhage that required caesarean section, right hemicolectomy and terminal ileum resection at 33 weeks of gestation. Spontaneous perforation associated with intestinal endometriosis in pregnancy is a rare complication, and only seven cases have been reported in the English literature. To the best of our knowledge, this is the first report of spontaneous ileal perforation due to endometriosis. Moreover, this is probably the first case of massive intestinal haemorrhage in pregnancy that resulted from intestinal endometriosis. These risks must be explained to couples suffering from endometriosis-related infertility prior to conception by assisted reproductive technology, and multidisciplinary management may be mandatory for women with severe endometriosis in pregnancy.

Vulvar varicosities are generally not an indication for a caesarean section but in a rare case of severe vulvar varicosities, it would be a controversial issue whether to perform a caesarean section for fear they might rupture during a vaginal delivery. We present a case of huge vulvar varicosities during pregnancy. MRI revealed obstruction of the internal iliac system by the gravid uterus and subsequent incompetence of a collateral pathway via the round ligament vein that emptied into the ovarian vein. The patient went into labour at 38 weeks, and successfully vaginally delivered a baby. The vulvar varicose veins became compressed by the foetal head from the inside, and markedly diminished in size during crowning and after delivery. Women with vulvar varicosities can be allowed to attempt a vaginal birth regardless of their severity. The use of MRI aids in the overall anatomical understanding of vulvar varicosities in pregnancy.

Management of second- and third-trimester fetal death in the presence of placenta previa is a dilemma for obstetricians. We herein describe a case of fetal death occurring at 23 weeks' gestation in the presence of placenta previa. Three weeks of expectant management failed to reduce uteroplacental blood perfusion evaluated with pulsatility index of the uterine artery. Labor was then induced with gemeprost vaginal pessary following overnight laminaria pretreatment. Vaginal delivery was achieved with total blood loss of 1900 ml. Homologous blood transfusion was obviated owing to autologous blood that had been stored during the waiting period.

objective: The objective of the study was to assess LOX-1 expression and Nrf2 activation in preeclamptic placentas and to manifest their physiological roles in preeclampsia. Methods: Expression and regulation of LOX-1, HO-1, and Nrf2 were evaluated by real-time quantitative RT-PCR and Western blotting. The functions of LOX-1 and Nrf2 were examined using an anti-LOX-1 antibody and Nrf2 activator in JAR, a choriocarcinoma cell line, and placental explants. Results: Both LOX-1 expression and Nrf2 activation were significantly decreased in preeclamptic placentas compared with normal controls. A significant decrease in LOX-1 mRNA was found in placental explant cultures under hypoxic conditions. Activation of Nrf2 up-regulated HO-1 in both the JAR cells and placental explants. Furthermore, oxLDL increased HO-1 mRNA, whereas the blockade of LOX-1 inhibited the increase of HO-1 mRNA in JAR cells. Conclusion: Decreasing LOX-1 expression in preeclamptic placenta may contribute to high oxLDL concentration, low Nrf2 activation, and low HO-1 expression. These findings provide novel insights into the crucial role of LOX-1 and Nrf2 in the pathogenesis of preeclampsia.

In the human placenta, embryo-derived trophoblasts aggressively invade maternal spiral arteries and transform the arteries to low-resistance large-caliber vessels. This process, which ensures adequate placental perfusion, is called maternal vascular remodeling. Histological examination showed deposition of maternal platelets in the trophoblast aggregates formed in the spiral arteries. Several lines of evidence suggest that these platelets are activated. Soluble factors released from the activated platelets, as a whole, enhanced invasive capacity of isolated trophoblasts in vitro. These findings suggest the importance of nonhemostatic platelet function in maternal vascular remodeling. In contrast, gene knockout studies suggest that maternal platelet defects are compatible with successful pregnancy in mice. Moreover, pregnant women with severe platelet defects usually accomplish an uneventful pregnancy. Thus, promotion of endovascular trophoblast infiltration by maternal platelets might not be the only mechanism that regulates maternal vascular remodeling. The maternal vascular remodeling is an essential component of human reproduction and should be secured by several complementary mechanisms. Future studies should aim to elucidate other mechanisms that could regulate endovascular trophoblast infiltration.