Ritsuo Honda

CD44 variant 6 is correlated with peritoneal dissemination and poor prognosis in patients with advanced epithelial ovarian cancer

Cancer stem cells (CSCs) drive tumor initiation and metastasis in several types of human cancer. However, the contribution of ovarian CSCs to peritoneal metastasis remains unresolved. The cell adhesion molecule CD44 has been identified as a major marker for CSCs in solid tumors, including epithelial ovarian cancer. CD44 exists as a standard form (CD44s) and also as numerous variant isoforms (CD44v) generated by alternative mRNA splicing. Here we show that disseminated ovarian tumors in the pelvic peritoneum contain highly enriched CD44v6‐positive cancer cells, which drive tumor metastasis and are responsible for tumor resistance to chemotherapy. Clinically, an increased number of CD44v6‐positive cancer cells in primary tumors was associated with a shortened overall survival in stage III–IV ovarian cancer patients. Furthermore, a subpopulation of CD44v6‐positive cancer cells manifested the ability to initiate tumor metastasis in the pelvic peritoneum in an in vivo mouse model, suggesting that CD44v6‐positive cells show the potential to serve as metastasis‐initiating cells. Thus, the peritoneal disseminated metastasis of epithelial ovarian cancer is initiated by the CD44v6‐positive subpopulation, and CD44v6 expression is a biomarker for the clinical outcome of advanced ovarian cancer patients. Given that a distinct subpopulation of CD44v6‐positive cancer cells plays a critical role in peritoneal metastasis, definitive treatment should target this subpopulation of CD44v6‐positive cells in epithelial ovarian cancer.

Hypertriglyceridemic acute pancreatitis during pregnancy: Prevention with diet therapy and ω-3 fatty acids in the following pregnancy

Acute pancreatitis complicating pregnancy is rare and has previously been associated with high mortality rates. We report a case of repeated hypertriglyceridemia during pregnancy. During the patients first pregnancy, acute pancreatitis was elicited in the third trimester by pregnancy-induced hypertriglyceridemia. The patient was treated successfully with a conservative treatment course. The hypertriglyceridemia recurred during her second pregnancy. She carried the pregnancy to term without incident while maintaining a diet low in fat diet and high in omega-3 fatty acids. Early diagnosis and intensive treatment can help to preserve the lives of the patient and the fetus. Prophylactic diet therapy and omega-3 fatty acids may prevent recurrent hypertriglyceridemia during pregnancy.

Transvaginal Methotrexate Injection for the Treatment of Cesarean Scar Pregnancy: Efficacy and Subsequent Fecundity

STUDY OBJECTIVE To investigate the efficacy of local methotrexate (MTX) injections under transvaginal ultrasound guidance for treatment of cesarean scar pregnancy (CSP) and to assess fecundity after treatment. DESIGN Retrospective review (Canadian Task Force classification II-3). SETTING University hospital. PATIENTS Eight women with CSP. INTERVENTION Transvaginal MTX injection. MEASUREMENTS AND MAIN RESULTS We retrospectively reviewed 8 CSP cases treated with local MTX injection under transvaginal ultrasonographic guidance. In all cases, the serum human chorionic gonadotropin concentration was monitored and the gestational sac was evaluated using ultrasonography after treatment. Magnetic resonance imaging was performed as necessary. Patient clinical characteristics, clinical course after treatment, treatment efficacy, and fecundity after treatment in patients desiring subsequent pregnancies were evaluated. All 8 women were successfully treated without the need for blood transfusions or surgical procedures, although 2 required additional MTX therapy via local injection or systemic administration. The mean (SD) time to human chorionic gonadotropin normalization was 78.5 (37.7) days (range, 42-166 days). Four of 5 patients desiring subsequent pregnancies after the treatment had uneventful parturition, and recurrent CSP was diagnosed in 1 patient. CONCLUSIONS Transvaginal MTX injection was effective and safe as sole treatment of CSP. Although the treatment course tended to be long, this method can be considered the first choice of treatment in patients desiring future pregnancies. However, careful attention should be paid to the possibility of CSP recurrence.

Rapid Detection of Chromosome Aneuploidies by Prenatal Interphase FISH (Fluorescence in situ Hybridization) and Its Clinical Utility in Japan

Objective: The purpose of this study was to assess the accuracy, informative rate, detection rate, and clinical utility of prenatal interphase fluorescence in situ hybridization (FISH) analysis of amniotic fluid samples from Japanese women.

Clinical use of colony-stimulating factor-1 in ovulation induction for poor responders.

OBJECTIVE To evaluate the benefit of colony-stimulating factor-1 (CSF-1) adjuvant therapy to poor responders during a controlled ovarian hyperstimulation (COH) cycle. DESIGN Prospective clinical study. SETTING University hospital, general hospital, and private IVF clinic in Japan. PATIENT(S) Thirty normogonadotropic patients who did not respond to conventional COH protocols. INTERVENTION(S) Eight million units of recombinant human CSF-1 were administered IV every other day during ovarian stimulation using FSH or hMG to 30 normogonadotropic poor responders. Serum CSF-1 concentrations were assayed on day 3. Additional studies were performed in a private IVF clinic on 27 poor responders with low serum CSF-1 levels. MAIN OUTCOME MEASURE(S) Pregnancy rates (PR). In addition, number of mature follicles, cycle cancellations, amount of required gonadotropins were documented. RESULT(S) Significantly more mature follicles, fewer cycle cancellations, and lower amounts of required gonadotropins were seen in the group treated with CSF-1. Five (16.7%) pregnancies were achieved. The CSF-1-effective patients displayed significantly lower serum CSF-1 concentrations. In a private IVF clinic, CSF-1 treatment increased the number of mature oocytes, fertilized eggs, and transferred embryos. Cycle cancellations decreased from 18.5%-3.7%; 11 pregnancies (40.7%) resulted from treatment. CONCLUSION(S) Concomitant administration of CSF-1 and hMG improved follicle developments, especially in patients with low serum CSF-1 levels in the early follicular phase.

Twisted Ovarian Tumor Causing Progressive Hemothorax : A Case Report of Porous Diaphragm Syndrome

Background: Porous diaphragm syndrome is caused by a defect in the diaphragm. The defect may induce pleural effusion in a patient with an ovarian tumor. Case Report: A 59-year-old Japanese woman with an ovarian tumor and right hemothorax underwent thoracotomy and presented with a fenestra in the right diaphragm through which bloody fluids were flowing from the peritoneal cavity into the pleural space. Following suturing of the fenestra, laparotomy revealed intraabdominal bleeding due to torsion of an ovarian tumor. Conclusion: This is the first report in which the diaphragmatic defect was identified in a patient with an ovarian tumor and hemothorax. Porous diaphragm syndrome may be involved in the pathophysiology of right pleural effusion observed in other medical conditions such as Meigs’ syndrome, ovarian hyperstimulated syndrome, and ovarian cancer.

Heterotopic cervical pregnancy with preservation of the intrauterine gestation

We present a case of heterotopic cervical pregnancy where intrauterine gestation was preserved successfully. A 40-year-old Japanese woman presented with heterotopic cervical pregnancy after intracytoplasmic sperm injection with elongated spermatid. An ultrasound examination showed heterotopic cervical pregnancy. Intrauterine gestation was preserved successfully with the use of local vasopressin injection, followed by curettage of cervical implantation and local methotrexate injection. The cervical pregnancy resolved, and a healthy full-term infant was delivered. When early diagnosis of a heterotropic cervical pregnancy is made, selective reduction of a cervical implantation might allow preservation of the intrauterine gestation, without hysterectomy.

Development of a mouse model for testing therapeutic agents: the anticancer effect of dienogest on endometrial neoplasms.

Abstract Objective: As the number of younger women with endometrial carcinoma has increased, fertility-sparing treatments have received more attention. Although there have been several reports on conservative treatments with progestins for endometrial carcinoma, only medroxyprogesterone acetate (MPA) is available in Japan. Dienogest has been developed as a fourth-generation progestin for treating endometriosis. Because of its high progesterone activity, its antitumor activity has attracted attention. In this study, we investigated the anticancer effect of dienogest on endometrial neoplasms using mouse model of endometrial carcinoma. Methods/materials: PtenloxP/loxP mice were injected with MPA or dienogest subcutaneously to evaluate the anticancer effect against endometrial neoplasms that developed in the mice. One week after injections, histopathological analyzes were performed. Results: Endometrial neoplasms were found in one of the eight (12.5%) mice from each group treated with either dienogest or MPA. In contrast, they were found in seven of eight (87.5%) mice not treated with progestins. Each progestin treatment showed anticancer activity against endometrial neoplasms that developed in the mice compared to those without treatment. Conclusions: Dienogest and MPA showed potent anticancer activity against endometrial neoplasms in our mouse model. The present study demonstrated that dienogest might be a useful therapeutic agent for human endometrial neoplasms.

Ovarian follicular development stimulated by leuprorelin acetate plus human menopausal gonadotropin in chimpanzees.

Abstract:  We attempted ovarian stimulation using gonadotropins in 14 chimpanzees. Subjects were given a single administration of leuprorelin acetate, followed by repeated administration of human menopausal gonadotropin (hMG) for 16–21 days. During the dosing period, the ovarian follicle diameter and count were measured by transvaginal ultrasonography. The hormone administration induced the development of multiple follicles, and multiple oocytes were subsequently retrieved. However, the follicle count was decreased, suggesting atresia, in some subjects. Statistically, the final follicle diameter was dependent on the dosing duration and the hMG dose in the late stage, while the maximum follicle count during hMG administration was dependent on age and the hMG dose in the early stage. Five subjects showed mild ovarian hyperstimulation syndrome (OHSS)‐like symptoms with a high serum estradiol (E2) concentration. These results suggest that leuprorelin acetate plus hMG administration successfully stimulates the development of multiple ovarian follicles for oocyte retrieval and that the serum E2 concentration is predictive of OHSS‐like symptoms in chimpanzees.

A Giant Ovarian Tumor Causing Anasarca and Dyspnea Successfully Managed after Preoperative Drainage

Serious complications are likely to accompany the treatment of giant ovarian tumors, and resection with or without preoperative drainage has been previously reported. Here, we report the case of a 27-year-old Japanese woman with a significant weight gain of 50 kg, who was referred to the Kumamoto University Hospital because of gait impairment and dyspnea. Imaging tests revealed an ovarian tumor, 37 cm in diameter, with two solid components. The patients condition improved after the removal of 31.5 l tumor fluid by using a suprapubic urinary catheter for 3 days. The tumor was subsequently resected without complications, and was diagnosed as a left mucinous ovarian tumor with malignant components, weighing 37 kg (81.5 lb). The patient was discharged after her anasarca improved, and her body weight decreased from 100 to 50 kg with accompanying considerable urination within two weeks. She was in good condition with no evidence of recurrence at 15 months after surgery. Tumor resection after preoperative drainage was effective in the management of a patient with dyspnea induced by a giant ovarian tumor. We suggest the use of a suprapubic urinary catheter for preoperative drainage because of its ease of use in preventing fluid leakage from the possibly malignant tumor.