Although moderate gastrointestinal toxicity was observed, oral CPA therapy contributed to improving the survival of heavily pretreated patients with recurrent epithelial ovarian cancer. A well-designed phase II trial in this regard is awaited.

Malignant struma ovarii is a rare type of ovarian tumor. Metastasis from malignant struma ovarii is rare and has only been documented in 5–6% of cases. The natural history and optimal treatment strategy for malignant struma ovarii remains controversial due to its rarity. The current report presents the case of a 45-year-old female who presented with a tumor of the rib bone. Following resection, the postoperative diagnosis was a metastasizing thyroid carcinoma. No abnormality was detected in the thyroid gland, however, computed tomography revealed a tumor in the left ovary. The patient underwent a left salpingo-oophorectomy and a wedge resection of the right ovary. The postoperative diagnosis was determined as a mature cystic teratoma with malignant struma ovarii (thyroid type, follicular carcinoma) of the left ovary and mature cystic teratoma of the right ovary. Four years subsequent to the initial diagnosis, multiple lung metastases were detected. The following chemotherapies were administered sequentially and intermittently: Tegafur-uracil, paclitaxel/carboplatin and oral etoposide. During this period, the metastatic lesions extended into the bone and progressed slowly. The patient continues to survive with the disease and 24 years have passed since the initial diagnosis, 20 years following the diagnosis of multiple lung metastates. The present report describes a rare case of malignant struma ovarii in which surgical resection and pathological examination of a metastatic rib tumor resulted in the identification of the primary ovarian lesion. The clinical behavior of malignant struma ovarii does not necessarily indicate a histological malignancy, therefore, prediction of future metastasis is difficult and the optimal treatment strategy for malignant struma ovarii is controversial. The present case indicates that the long-term use of oral anticancer agents may facilitate the maintenance of tumor dormancy.

Unrecognizable exposure to estrogenic substance may cause estrogen-dependent diseases, endometriosis and cancer. Pregnant mice (ICR/Jcl, CLEA) were exposed to 0.01 mg ethinyl estradiol (EE2)/kg per day or vehicle (olive oil) through oral intubation from day 11 to 17 of gestation. They delivered their offspring and raised them. When the experimental female F1 mice were at 8 weeks of age, they were not exposed to EE2 or to the same dose of EE2 or to vehicle twice a week until 20 weeks of age. The control female F1 mice were exposed to the same dose of EE2 or vehicle alone, similarly. All mice were killed at 28 weeks of age. The resected uteri and ovaries were processed for microscopic examinations and for determination of the aromatase mRNA levels and aromatase protein through quantitative RT-PCR and Western blotting, respectively. Adenomyosis and adenocarcinomatous changes were significantly discernible in the EE2-exposed uteri, and incidence of ectopic glands and serous cysts were significantly increased in the prenatally EE2-exposed ovaries as compared with respective controls. Significant upregulation of the aromatase mRNA was seen in the prenatally EE2-exposed uteri and in the EE2-exposed ovaries. The aromatase protein was identified in all ovaries examined, and in EE2-exposed uteri but not in controls and confirmed its localization in eutopic and ectopic glands, abnormally proliferated lesions and the lining of the cysts. Taken together, continuous EE2 exposure may cause endometriotic and precancerous lesions due to excessive estrogen synthesis in both target organs.

Preliminary findings of various types of globin expressed in the respiratory bronchiolar and alveolar epithelium prompted us to compare the expression of erythropoietin (Epo) and its receptor (EpoR) in normal (healthy) human lung tissues with that in malignant lung tissues. The expression of Epo and EpoR was examined at the transcriptional and protein levels in normal and malignant lung tissues by reverse transcription-PCR, western blot, and immunohistochemical analyses. EpoR mRNA, but not Epo mRNA, was detected in all samples. In normal tissues, EpoR was detected in the mesothelium, chondrocytes, alveolar cells, vascular endothelial cells, smooth muscle fibers, macrophages, and neutrophils, while in malignant foci, the cancer cells of five malignant types showed various intensities of EpoR immunoreactivity. The pattern of staining of EpoR protein was generally stronger in the malignant tissues than in the normal samples. Phosphorylation of the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK-ERK1/2) was frequently seen in malignant cells, but not in the normal tissues, with the exception of macrophages. Based on the expression of Epo and EpoR mRNA with the EpoR in almost all cell components in normal tissues, we suggest that the normal lung may produce various types of globin through the autocrine and/or paracrine role of Epo. When the Epo signal is upregulated by hypoxic stress, the normal cells appear to transform into malignant cells and proliferate through activated MAPK signaling.

We report a mother and newborn in the puerperium with hemorrhage secondary to factor VIII inhibitor. A 31-year-old gravida 1 para 1 delivered at a local clinic with a massive postpartum hemorrhage. The activated partial thromboplastin time was prolonged and factor VIII inhibitor was detected. The persistent hemorrhage improved following treatment, including transfusion, steroid therapy, and bypass therapy with factor VII formulations. After hysteroscopic removal of the retained placenta, the hemorrhage decreased. The newborn developed significant swelling of the hands after routine blood sampling and factor VIII inhibitor was detected. The inhibitor disappeared without any special treatment in the 5th month postpartum in the mother and the 4th month postpartum in the newborn. Factor VIII inhibitor may be transferred via the placenta from the mother to the fetus. Therefore, the newborn should also be carefully observed in a case of massive hemorrhage after delivery.