Introduction/Background The present study was designed to evaluate the effect of the peritoneal stripping method termed ‘wide resection of the pelvic peritoneum (WRPP)’ on eliminating disseminated tumors in the pelvic peritoneum and whether there is any survival benefit for patients with epithelial ovarian cancer. Methodology From January 2000 to December 2018, 460 patients with epithelial ovarian cancer were treated surgically at Kumamoto University Hospital. The clinical and surgical records of these patients were reviewed retrospectively, and 225 patients with ovarian cancer who underwent standard definitive surgery were included in this study. Eligible patients with ovarian cancer were divided into 3 groups according to surgical approach. Patients in the standard surgery group underwent cytoreduction with standard surgical techniques (n=65). The WRPP group consisted of patients who underwent standard surgery plus WRPP (n=125). The RS group included patients who required standard surgery plus rectosigmoidectomy (RS) (n=35). The primary outcome measure was overall survival. The secondary endpoint was recurrence-free survival. Results Overall survival was significantly longer in the WRPP group than in the standard surgery group for patients with stage III–IV disease (P<0.05). The WRPP group was less prone to recurrence than the standard surgery group (P=0.70). In addition, the intrapelvic recurrence rate differed significantly between the standard surgery and WRPP groups (38.2% vs. 23.8%, P<0.01). Conclusion WRPP is an effective procedure that should be a part of the skill set of any gynecological surgeon performing surgical cytoreduction in patients with advanced ovarian cancer. The addition of this surgical technique has the potential to improve patient outcomes. Disclosure Nothing to disclose.

Introduction/Background In Japan, radical hysterectomy (RH) has been widely performed for patients with invasive uterine cervical cancer, resulting in favorable outcome. However, recurrence, which might have been induced by hematogenous metastasis, is defined as the development of distant metastasis in some cases. From 2006, we have performed RH with antecedent ligation of uterine vessels before pelvic lymphadenectomy to prevent hematogenous metastasis. The objective of this study is to evaluate the clinical contribution of antecedent ligation of uterine vessels in RH to the prognosis of patients with uterine cervical cancer. Methodology Two hundred fifty-five patients who underwent RH at Kumamoto University Hospital between 2000 and 2011 were identified. Retrospective analyses were performed between 2 groups according to the surgical approach. The patients who underwent RH with conventional surgical procedures before 2006 were assigned to conventional surgery group (n=98). Another group (antecedent ligation group) consisted of patients who underwent RH with a pelvic lymphadenectomy following antecedent ligation of uterine vessels after 2006 (n=157). The site of initial recurrence within 5 years and histological type were analyzed. Survival estimates used the Kaplan-Meier methods. Results At a median follow-up of 88 months, 49 events had been observed and 31 patients had died. The 5-year overall survival rates were similar between groups (83.7% vs 90.4%, p=0.12). Among squamous cell carcinoma (SCC) patients, there were no differences in the 5-year overall survival rates and recurrences between groups. For non-SCC patients, RH with antecedent ligation of uterine vessels improved the 5-year overall survival rates (70.3% vs 88.0%, p=0.06). Furthermore, antecedent ligation of uterine vessels in RH was associated with a lower rate of extrapelvic recurrence than conventional surgery (21.6% vs 6.0%, p=0.03) in patients with non-SCC uterine cervical cancer. Conclusion Antecedent ligation of uterine vessels in RH may improve the survival in patients with non-SCC uterine cervical cancer. Disclosure Nothing to disclose.

Saffron (Crocus Sativus L.) has been utilized in the preparation of different foods all over the world due to its organoleptic properties (color, taste, and flavor), and it also shows therapeutic properties against miscellaneous diseases in traditional medicine. Crocin, picrocrocin, and safranal are the main bioactive compounds of saffron and possess various health beneficial properties. Crocins also belong to the category of water-soluble carotenoids that make them unique natural food colorant alternatives for a variety of food applications. They also have shown to possess anticarcinogenic, antidepressant, antiinflammatory, antioxidant, antiapoptotic, and antithrombotic properties. However, the bioactive compounds of saffron are unstable to various environmental conditions such as temperature, pH, light, oxygen, and the presence of metallic ions, and can be degraded in the gastrointestinal environment that results in low bioavailability and restrict their applications. The aim of this chapter is to evaluate the encapsulation methods mainly spray drying, freeze-drying, ionic gelation, inclusion complexation, electrospinning, nanoparticle, emulsion, liposome and solid lipid nanoparticle preparations that aim to prevent the degradation of those compounds by environmental factors, the destruction in human gastrointestinal tract, and to provide controlled release of compounds and therefore improve their bioavailability.

ObjectiveThe most commonly proposed mechanisms for pain production in endometriosis are: 1) production of substances such as cytokines and growth factors released from activated macrophages and other cells; 2) direct and indirect effects of active bleeding from endometriotic implants; and 3) irritation or direct invasion of pelvic floor nerves induced by infiltrating endometriotic implants with the mechanism of ‘epithelial to mesenchymal transition’ (EMT). The use of Tranilast, an anti-allergic drug, was approved in 1982 in Japan and South Korea for treatment of bronchial asthma. It is a relatively safe drug that is well tolerated by most patients at doses of up to 600 mg/day. It reduces collagen synthesis in fibroblasts, inhibits growth of neurofibroma cells, and produces interleukin-6 in endothelial cells that processes EMT in vitro. In this preliminary clinical trial, we evaluated the efficiency of Tranilast that was given to 8 patients of endometriosis with pelvic pain.DesignClinical trial.Materials and MethodsThis study was carried out with the approval from IRB of Kumamoto University. Tranilast was administered to patients with adenomyosis or endometriosis complaining of pelvic pain at a dose of 300mg/day for six months. The patients continued to record the degree of pain every day in the Numerical Rating Scale (NRS), which is based on a scale from 0 to 10; 0 represents no pain and 10 represents the worst possible pain.ResultsThe average NRS score of low back pain or lower abdominal pain during menstruation period decreased from 6.25 to 3.63 at the end of the administration. One of eight patients showed a decrease in score of 70% or more (markedly improved). Four patients showed a 69-50% score reduction rate. In addition, three patients who were suffering with severe pain no longer required bed rest.ConclusionTranilast is considered a useful drug to relieve the symptoms of pelvic pain of endometriosis by mechanisms different from the drug to control the ovarian endocrinological function. ObjectiveThe most commonly proposed mechanisms for pain production in endometriosis are: 1) production of substances such as cytokines and growth factors released from activated macrophages and other cells; 2) direct and indirect effects of active bleeding from endometriotic implants; and 3) irritation or direct invasion of pelvic floor nerves induced by infiltrating endometriotic implants with the mechanism of ‘epithelial to mesenchymal transition’ (EMT). The use of Tranilast, an anti-allergic drug, was approved in 1982 in Japan and South Korea for treatment of bronchial asthma. It is a relatively safe drug that is well tolerated by most patients at doses of up to 600 mg/day. It reduces collagen synthesis in fibroblasts, inhibits growth of neurofibroma cells, and produces interleukin-6 in endothelial cells that processes EMT in vitro. In this preliminary clinical trial, we evaluated the efficiency of Tranilast that was given to 8 patients of endometriosis with pelvic pain. The most commonly proposed mechanisms for pain production in endometriosis are: 1) production of substances such as cytokines and growth factors released from activated macrophages and other cells; 2) direct and indirect effects of active bleeding from endometriotic implants; and 3) irritation or direct invasion of pelvic floor nerves induced by infiltrating endometriotic implants with the mechanism of ‘epithelial to mesenchymal transition’ (EMT). The use of Tranilast, an anti-allergic drug, was approved in 1982 in Japan and South Korea for treatment of bronchial asthma. It is a relatively safe drug that is well tolerated by most patients at doses of up to 600 mg/day. It reduces collagen synthesis in fibroblasts, inhibits growth of neurofibroma cells, and produces interleukin-6 in endothelial cells that processes EMT in vitro. In this preliminary clinical trial, we evaluated the efficiency of Tranilast that was given to 8 patients of endometriosis with pelvic pain. DesignClinical trial. Clinical trial. Materials and MethodsThis study was carried out with the approval from IRB of Kumamoto University. Tranilast was administered to patients with adenomyosis or endometriosis complaining of pelvic pain at a dose of 300mg/day for six months. The patients continued to record the degree of pain every day in the Numerical Rating Scale (NRS), which is based on a scale from 0 to 10; 0 represents no pain and 10 represents the worst possible pain. This study was carried out with the approval from IRB of Kumamoto University. Tranilast was administered to patients with adenomyosis or endometriosis complaining of pelvic pain at a dose of 300mg/day for six months. The patients continued to record the degree of pain every day in the Numerical Rating Scale (NRS), which is based on a scale from 0 to 10; 0 represents no pain and 10 represents the worst possible pain. ResultsThe average NRS score of low back pain or lower abdominal pain during menstruation period decreased from 6.25 to 3.63 at the end of the administration. One of eight patients showed a decrease in score of 70% or more (markedly improved). Four patients showed a 69-50% score reduction rate. In addition, three patients who were suffering with severe pain no longer required bed rest. The average NRS score of low back pain or lower abdominal pain during menstruation period decreased from 6.25 to 3.63 at the end of the administration. One of eight patients showed a decrease in score of 70% or more (markedly improved). Four patients showed a 69-50% score reduction rate. In addition, three patients who were suffering with severe pain no longer required bed rest. ConclusionTranilast is considered a useful drug to relieve the symptoms of pelvic pain of endometriosis by mechanisms different from the drug to control the ovarian endocrinological function. Tranilast is considered a useful drug to relieve the symptoms of pelvic pain of endometriosis by mechanisms different from the drug to control the ovarian endocrinological function.

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.

Human gonads and non-gonadal organs/tissues express luteinizing hormone/chorionic gonadotropin (LH/CG) receptors. This study aimed to identify the LH/CG receptors and to clarify their function in human placental chorionic villous macrophages. Macrophages as well as syncytiotrophoblasts of human chorionic villous tissues were immunohistochemically positive for LH/CG receptor throughout gestation. By reverse transcription-nested polymerase chain reaction methods, villous macrophages were shown to express a variant type of LH/CG receptor, the sequencing of which revealed a deletion of exon 9. For experiments in vitro, a monocyte-macrophage cell line, THP-1, was transfected with vector alone, wild-type LH/CG receptor, and exon 9-deleted LH/CG receptor after phorbol 12-myristate 13-acetate (PMA) treatment. Non-PMA-treated THP-1 cells transfected with vector alone were also examined. THP-1 cells expressed exon 9-deleted LH/CG receptor after treatment with PMA. After the cells of the four groups were cultured in medium containing intact human CG (hCG), the concentrations of hCG and its beta-core fragment (beta-CF) were measured in the supernatant of the culture medium and in the cell cytosol. Time-dependent hCG uptake was observed in both non-PMA-treated and PMA-treated THP-1 cells, suggesting that the variant receptor is not directly involved in the ingestion of hCG. The degradation of hCG and excretion of beta-CF were progressed in PMA-treated cells but not in the un-treated cells. In the cell cytosol, the ratio of beta-CF and hCG concentrations (beta-CF/hCG) was significantly higher in the PMA-treated cells than in non-PMA-treated cells; however, it did not differ between the PMA-treated cells transfected with exon 9-deleted receptor and those transfected with vector alone. Macrophages may express the variant receptor in order to recognize the intracytoplasmic hCG and transport it to the lysosome. Among the two PMA-treated cells, the ratio was lower in those transfected with wild-type receptor. The expression of the variant receptor may modulate the degradation of hCG but be reduced by expression of the wild-type receptor in its lacking macrophages. Our data suggest a potentially important role for exon 9-deleted LH/CG receptors expressed in human placental villous macrophages in the local metabolism of hCG.

The human ovarian surface epithelium (hOSE) is a single layer of mesothelial-type primitive epithelial cells that are potential estrogen targets. It has been reported that hOSE cells can produce estrogen. However, the mechanisms that regulate estrogen level(s) in hOSE cells are not yet known. To elucidate the enzymes involved in these reactions, we examined gene expression of 17beta-hydroxysteroid dehydrogenases (17beta-HSDs) in primary hOSE (POSE) and OSE2a cells using RT-PCR. We found that POSE cells and cells of the immortalized hOSE line, OSE2a, bidirectionally converted estrone (E1) and 17beta-estradiol (E2). Both cell types expressed mRNA for 17beta-HSD type 1 (17beta-HSD1), suggesting that the enzyme is involved in the E1 to E2 conversion. Interestingly, both cells expressed 17beta-HSD4 mRNA but not 17beta-HSD2 mRNA. We prepared an antibody against the carboxyl terminal of 17beta-HSD4 (anti-17beta-HSD4 antibody), which recognized the 80 and 48 kDa proteins in POSE and OSE2a cells based on immunoblot analysis. Furthermore, immunohistochemical study revealed the presence of 17beta-HSD4 in hOSE cells in the human ovary. These results suggest that 17beta-HSD4 is involved in estrogen inactivation and may protect against an excessive accumulation of E2 in hOSE cells.