Oestrogen-dependent hypothalamic oxytocin expression with changes in feeding and body weight in female rats.

Oxytocin (OXT) is produced in the hypothalamic nuclei and secreted into systemic circulation from the posterior pituitary gland. In the central nervous system, OXT regulates behaviours including maternal and feeding behaviours. Our aim is to evaluate whether oestrogen regulates hypothalamic OXT dynamics. Herein, we provide the first evidence that OXT dynamics in the hypothalamus vary with sex and that oestrogen may modulate dynamic changes in OXT levels, using OXT-mRFP1 transgenic rats. The fluorescence intensity of OXT-mRFP1 and expression of the OXT and mRFP1 genes in the hypothalamic nuclei is highest during the oestrus stage in female rats and decreased significantly in ovariectomised rats. Oestrogen replacement caused significant increases in fluorescence intensity and gene expression in a dose-related manner. This is also demonstrated in the rats' feeding behaviour and hypothalamic Fos neurons using cholecystokinin-8 and immunohistochemistry. Hypothalamic OXT expression is oestrogen-dependent and can be enhanced centrally by the administration of oestrogen.

Prognostic significance of intra-tumoral budding in high-grade serous ovarian carcinomas.

Intra-tumoral budding (ITB) has been well demonstrated to be an independent risk factor for adverse outcomes in colorectal carcinoma. This study investigated the prognostic significance of ITB in high-grade serous ovarian carcinomas (HGSOCs). The medical records and slides of 84 SOCs, including 13 with neoadjuvant chemotherapy (NAC), were retrospectively reviewed. The histopathologic examination with scoring of p53 expression showed them to be 80 HGSOCs and 4 low-grade serous ovarian carcinomas (LGSOCs). ITB was found in 64 (80.0%) of the 80 HGSOCs and 1 (25.0%) of 4 LGSOCs. The presence of ITB in HGSOC was significantly correlated with a higher level of CA125, an advanced 2014 FIGO stage, the presence of Lymph node metastasis, and the presence of lymphovascular space invasion (LVSI). The median progression-free survival (PFS) was 18 months in patients with HGSOC with ITB and 36 months in patients with HGSOC without ITB (P = 0.006), and their median overall survival (OS) was 50 months and 60 months (P = 0.060). The multivariate analysis revealed that ITB was not an independent prognostic factor. ITB is a cost-effective prognostic indicator for patients with HGSOC and ITB in ovarian tumor tissue is considered a useful histological biomarker of the progression of HGSOCs.

A retrospective study for investigating the relationship between old and new staging systems with prognosis in ovarian cancer using gynecologic cancer registry of Japan Society of Obstetrics and Gynecology (JSOG): disparity between serous carcinoma and clear cell carcinoma.

OBJECTIVE: International Federation of Gynecology and Obstetrics (FIGO) staging for ovarian, fallopian tube, and peritoneal cancers was revised in 2014. The aim of this study is to clarify whether the revised FIGO2014 staging reflects the prognosis of patients with ovarian cancer by histological type in Japan. METHODS: We extracted 9,747 patients who were diagnosed with ovarian cancer since 2004 until 2008 and who could be classified into appropriate stages from the Gynecologic Cancer Registry of Japan Society of Obstetrics and Gynecology. These cases were analyzed after revision to FIGO2014 based on the pTNM classification. RESULTS: Among stage I, the 5-year overall survival rate (5y-OS) in FIGO2014 was 94.9% in stage IA, 92.3% in stage IC1, 86.1% in IC2, and 84.9% in IC3 with significant differences between stages IA and IC1 (p=0.012), IC1 and IC2 (p<0.001). There was a significant difference between stages IA and IC1 in clear cell and mucinous carcinoma but not in serous and endometrioid carcinoma. Among stage III, the 5y-OS was 75.6% in stage IIIA1, 68.9% in IIIA2, 58.6% in IIIB, and 44.4% in IIIC, with significant differences between stages IIIA2 and IIIB (p=0.009), IIIB and IIIC (p<0.001). Among stage IV, the 5y-OS was 43.1% in stage IVA* and 32.1% in IVB with a significant difference (p=0.002). CONCLUSION: The results suggest that changes in classification for stage III and stage IV are appropriate, but the subclassification for stage IC might be too detailed. There was a discrepancy of prognosis by histological type between stage IA and IC1.

Trends in Uterine Cervical Cancer Screening at Physical Health Checkups for Company Employees in Japan.

The consultation rate for uterine cervical cancer screening in Japan is markedly low in comparison with other developed countries. The purpose of this study is to investigate the trends in uterine cervical cancer screening during regular company checkups and to identify potential problems. Questionnaires were sent to occupational health physicians through Sansuiken (Alumni Association of the University of Occupational and Environmental Health, Japan). Overall, 127 valid responses showed that Papanicolaou (Pap) tests are conducted in 100 companies (79%). The detailed information from 50 of the 100 responses was analyzed. Mandatory cervical cancer screenings are performed at just 6 companies (12%). Pap test are started at 30 years of age at 9 of 49 companies, and only 18 of 49 companies (37%) start Pap tests for employees at 20 years old. Of the 86,695 women, 31,294 (36%) received cervical cancer screening. Abnormal Pap test results were detected in 3.0%. Although cervical cancer screening rates have slightly increased compared to our previous studies (17% in 2004, 23% in 2008), it remains at a low level. Complete examinations with colposcopy and punch biopsy were carried out in 70% (61 of 87 women) of those with an abnormal Pap test. Twelve of 26 companies had no information about detailed examination results. It is important to note that cervical cancer incidence and mortality are increasing among young women in Japan. Occupational physicians and health nurses should manage female health education and care at the workplace, by including uterine cervical cancer screening in the growing female working population.

Adenocarcinoma of intestinal type of the vulva.

Primary adenocarcinoma of the vulva is a rare disease, and usually arises in a Bartholin gland or occurs in association with Paget's disease. Furthermore, adenocarcinoma of intestinal type of the vulva is an extremely rare neoplasm, and few cases have been reported. The appropriate treatment for optimal prognosis is unclear. We report a case of adenocarcinoma of intestinal type of the vulva occurring in a 63-year-old female. The tumor was found near the urethra, and biopsy specimen showed a proliferation of signet ring cells embedded in an abundant myxoid stroma and irregular tubular structures of atypical columnar epithelium. An extensive workup showed no metastases. Local excision with a 2-cm lesion in the vulva side, bilateral superficial inguinal lymph node dissection and Cloquet lymph node biopsy were performed. Cancer cells contained mucinous materials in the cytoplasm, which exhibited diffuse positive staining for cytokeratin 20 and CDX2. The final pathologic diagnosis was adenocarcinoma of intestinal type of the vulva (pT1bN0M0). The patient received adjuvant external irradiation because of positive urethral surgical margin. She is well 1 year after therapy. Immunohistochemical staining for cytokeratin 20 and polyclonal CDX2 is helpful with investigation of adenocarcinoma of intestinal type, but long-term prognosis remains unclear.

Laparoscopic uterosacral ligament colpopexy for apical support in addition to hysterectomy for pelvic organ prolapse.

AIM: To evaluate the perioperative complications and the anatomical outcomes of our laparoscopic uterosacral ligament (USL) colpopexy, which is a novel laparoscopic technique for the management of uterine prolapse. The objective was to report on outcome after 2 years of a technique using laparoscopic USL colpopexy. METHODS: A total of 152 uterine prolapse patients underwent laparoscopic USL colpopexy from May 2013 to April 2015. We described the surgical technique and performed a retrospective analysis of this laparoscopic technique. Patients underwent standardized assessment and examination using pelvic organ prolapse quantification (POP-Q) score. The dependent values of Ba point (bladder), C point (vaginal cuff) and Bp point (rectum) were recorded preoperatively, and at 1, 3, 6, 12 and 24 months of postoperative examination. Pre/postoperative data were compared using the Kaplan-Meier method. RESULTS: Mean age, operative time and amount of hemorrhage were 68.2 ± 7.5 years, 118.3 ± 36.4 min and 60.5 ± 73.3 mL, respectively. Overall recurrent prolapse, which was defined as POP-Q stage II or higher, was noted in 29 patients (19%). However, only 2 patients presented recurrent rectocele among 51 patients with preoperative POP-Q stage II of uterine prolapse alone (recurrence rate; 3.9%). The pre/postoperative average POP-Q scores were -0.2/-2.7 cm (P < 0.05) at Ba point, -1.9/-5.1 cm (P < 0.05) at C point and -2.4/-2.3 cm (P = 0.06) at Bp point. CONCLUSION: Laparoscopic visualization of uterosacral ligaments may result in safe colpopexy. Our results show this will be a useful procedure for apical support as native tissue repair.

Evaluation of laparoscopic-guided rectus sheath block in gynecologic laparoscopy: A prospective, double-blind randomized trial.

BACKGROUND: Ultrasound-guided nerve blocks are effective; however, their use in the abdominal wall is reportedly associated with a risk of abdominal organ injury. Laparoscopic-guided nerve blocks are thought to be safer than ultrasound-guided nerve blocks. We evaluated the safety and effectiveness of the laparoscopic-guided rectus sheath block (LGRSB) for umbilical incisions after gynecologic laparoscopy. MATERIALS AND METHODS: A single-center, prospective, randomized controlled trial of 210 women who underwent gynecologic laparoscopy was performed at a university teaching hospital in Japan. The intervention group underwent the LGRSB with ropivacaine hydrochloride at the end of laparoscopy under general anesthesia and received regular care. The control group received only regular care without a field block. The postoperative pain score (PPS) was recorded at 6 and 12 h and 1, 2, and 3 days postoperatively. The PPS and use of postoperative analgesics (loxoprofen, diclofenac, and pentazocine) were recorded by the floor nurses, who were blinded to the patients' data. RESULTS: In total, 107 women in the intervention group and 101 women in the control group were analyzed. No adverse events were encountered throughout this study. There was no evidence of differences in the PPS or use of perioperative opioids and postoperative analgesics. CONCLUSION: The LGRSB for umbilical incisions after laparoscopic gynecology was easy and safe. However, this method did not significantly reduce the PPS at rest or during coughing in all postoperative conditions after gynecologic laparoscopy compared with the control.

Aiming for complete safety of first trocar insertion of laparoscopic surgery: usefulness of preoperative ultrasonography of umbilical region.

AIM: Vascular or intestinal injuries at the time of the first trocar insertion can cause serious complications during laparoscopic surgeries. In this study, we evaluate the usefulness of ultrasound scans of the umbilical region as well as intraumbilical conditions to help prevent serious complications. METHODS: The subjects included 430 cases who underwent laparoscopic gynecologic surgeries. The umbilical ultrasound scan was performed after tracheal intubation to observe the intestinal movements associated with respiration. Structures of the umbilical region as well as peristalsis and the movement of the intestinal tract were observed. Then, the thickness of the subcutaneous fat (between the umbilical skin surface and the rectus fascia) and the preperitoneal fat (between the rectus fascia and the peritoneum) were measured. The relationship between body mass index (BMI), insertion time of the first trocar and ultrasound measurements were analyzed. RESULTS: The anatomical structures of the umbilical region (the subcutaneous tissue and the preperitoneal fat) were clearly observed in all cases. The BMI score had a significant relationship with subcutaneous fat thickness (r = 0.547), but remarkably not with preperitoneal fat thickness (r = 0.174). There was no significant relationship between BMI and insertion time. However, insertion time of the first trocar had a significant relationship with preperitoneal fat thickness (r = 0.534). CONCLUSIONS: Preoperative ultrasonography of the umbilical region is asimple process, and it is helpful inpreventing serious complications caused by the first trocar insertion. We have found that preperitoneal fat thickness seems to be an important factor in predicting the potential difficulty of the first trocar insertion.

Efficacy of palonosetron plus dexamethasone in preventing chemotherapy-induced nausea and emesis in patients receiving carboplatin-based chemotherapy for gynecologic cancers: a phase II study by the West Japan Gynecologic Oncology Group (WJGOG 131).

OBJECTIVE: Palonosetron is effective for the management of acute and delayed chemotherapy-induced nausea and vomiting (CINV). While emetogenic carboplatin-based chemotherapy is widely used to treat gynecologic cancers, few studies have evaluated the antiemetic effectiveness of palonosetron in this setting. METHODS: A multicenter, single-arm, open-label phase II trial was conducted to evaluate the safety and effectiveness of palonosetron in controlling CINV in patients with gynecologic cancer. Chemotherapy-naïve patients received intravenous palonosetron (0.75 mg/body) and dexamethasone before the infusion of carboplatin-based chemotherapy on day 1. Dexamethasone was administered (orally or intravenously) on days 2-3. The incidence and severity of CINV were evaluated using the patient-completed Multinational Association of Supportive Care in Cancer Antiemesis Tool and treatment diaries. The primary endpoint was the proportion of patients experiencing complete control (CC) of vomiting, with "no rescue antiemetic medication" and "no clinically significant nausea" or "only mild nausea" in the delayed phase (24-120 hours post-chemotherapy). Secondary endpoints were the proportion of patients with a complete response (CR: "no vomiting" and "no rescue antiemetic medication") in the acute (0-24 hours), delayed (24-120 hours), and overall (0-120 hours) phases, and CC in the acute and overall phases. RESULTS: Efficacy was assessable in 77 of 80 patients recruited. In the acute and delayed phases, the CR rates the primary endpoint, were 71.4% and 59.7% and the CC rates, the secondary endpoint, were 97.4% and 96.1%, respectively. CONCLUSION: While palonosetron effectively controls acute CINV, additional antiemetic management is warranted in the delayed phase after carboplatin-based chemotherapy in gynecologic cancer patients (Trial registry at UMIN Clinical Trials Registry, UMIN000012806).

Aging and uterine serous carcinoma.

Uterine serous carcinoma (USC) is closely associated with advanced age in patients. The p53 signature (p53S) is considered the earliest indication for the presence of carcinogenesis of USC. Based on our previous studies, the presence of p53Ss have almost always been found in elderly women and are suspected of being responsible for the imbalance between the proliferation and apoptosis of endometrial epithelial cells with advanced age. We have summarized the current state of knowledge regarding the association between age and cancer and propose an age-related type of endometrial cancer instead of Type II estrogen-independent endometrial cancer.

Inhibition of WNT/ß-catenin signaling under serum starvation and hypoxia induces adipocytic transdifferentiation in human leiomyoma cells.

Fatty metamorphosis is an uncommon alteration in uterine leiomyoma (i.e., lipoleiomyoma), and the pathogenetic mechanisms underlying this phenomenon remain poorly understood. Because a conditional deletion of ß-catenin, a major transducer of the canonical Wingless/integrated (WNT) pathway, in the developing mouse uterus can induce adipogenesis in the myometrium, it is hypothesized that inhibition of the WNT/ß-catenin signaling may be also involved in the development of fat cells within uterine leiomyoma. In the current study, which was performed to address this point, intracytoplasmic lipid droplets were detectable in cultured human leiomyoma cells by treatment with a potent tankyrase inhibitor, XAV939, which antagonizes ß-catenin, in a serum-starved culture medium without additional adipogenesis-inducing agents or supplements, and showed increasing accumulation in a time-dependent manner. In addition, the induction of fat cells was greatly enhanced under hypoxic conditions (i.e., 2.5% O2)-recapitulating the local in vivo situation of uterine leiomyoma-in comparison to that under normoxic conditions (i.e., 21% O2). The marker genes of differentiated fat cells such as ADIPOQ and PLIN were highly expressed in leiomyoma cells that were treated with XAV939 under hypoxia and serum starvation, whereas the immunohistochemical expression of desmin-a cytoskeletal protein representing smooth muscle differentiation-was downregulated, which appears in line with the switch in differentiation. The results of our study suggest that the inhibition of canonical WNT/ß-catenin signaling under the stress due to hypoxia and serum starvation can initiate adipocytic transdifferentiation or metaplasia in human uterine leiomyoma cells, which is potentially related to the development of lipoleiomyoma.

Expression of N-Acetylgalactosaminyltransferase-6 Is Related to Expression of Cell Adhesion Molecules in Endometrial Cancer.

BACKGROUND: The aberrant glycosylation of mucin type O-glycans is thought to be associated with functional alteration of cancer cells, including adhesive properties, as well as their potential for invasion and metastasis. Positive expression of N-acetylgalactosaminyltransferase-6 (GalNAc-T6) may also be a marker for aberrant O-glycans in carcinogenesis. We previously reported that over-expression of GalNAc-T6 had a strong association with endometrial cell invasion ability in vitro. MATERIALS AND METHODS: This study investigated the relationship between GalNAc-T6 expression and cell adhesion molecules in 218 endometrial carcinomas by immunohistochemistry. RESULTS: Expression of GalNAc-T6 was found to be significantly related to expression of E-cadherin. Positive expression of GalNAc-T6 was significantly associated with better histological grade and good clinical prognosis of patients, but positive E-cadherin and ß-catenin expression were not significantly associated with improved overall survival. CONCLUSION: GalNAc-T6 might be related to cell-cell adhesion in the early phase of cancer invasion in endometrial carcinoma.

Expression of Polypeptide N-Acetylgalactosaminyltransferase-6 in Epithelial Ovarian Carcinoma.

BACKGROUND: The family of polypeptide N-acetylgalactosanimyltransferases (GalNAc-Ts) are important factors in glycosylation in carcinomas. The purpose of this study was to investigate the clinical significance of GalNAc-T6 and its correlation with the prognosis of epithelial ovarian carcinoma. MATERIALS AND METHODS: A total of 150 patients with epithelial ovarian carcinoma were enrolled and the relationship between GalNAc-T6 expression by immunohistochemistry and long-term survival was evaluated. RESULTS: The expression of GalNAc-T6 was positive in 57.6% (34/59) of those with serous carcinoma, 85.3% (29/34) in mucinous carcinoma, 15.6% (5/27) in clear cell carcinoma, and 44% (14/25) in endometrioid carcinoma. In a Kaplan-Meier analysis of patients with grade 1 or 2 serous carcinoma, the 10-year overall survival rates were 47.4% in the GalNAc-T6-positive and 9.1% in the GalNAc-T6-negative groups (p=0.047). CONCLUSION: GalNAc-T6 expression in epithelial ovarian carcinoma was different according to pathological type. In low-grade serous carcinoma, GalNAc-T6 expression may contribute to improved long-term survival.

GalNAc-T6 in the relationship with invasion ability of endometrial carcinomas and prognostic significance.

O-glycosylation in the field of carcinogenesis has been a critical topic of concern for several decades. The abnormal function of enzymes catalyzing the first step of this process, named polypeptide N-acetylgalactosaminyltransferases (ppGalNAc-Ts) has been determined to play an important role in cancer development and metastasis. Accordingly, we investigated the expression of GalNAc-T6 in endometrial carcinoma and evaluated the relationship between invasion characteristics and the cellular level of GalNAc-T6. The results suggested that positive GalNAc-T6 expression is significantly associated with histological grade of tumors and myometrial invasion characteristic. In vitro experiments showed that the over expression of GalNAc-T6 had strong association with the decrease of endometrial cell invasiveness. Taken together, our data support the use of GalNAc-T6 as a potential indicator of good prognosis and noninvasive tumor in patients with endometrial carcinoma.

Effect of menopause on hormonal receptors in ampullae of the fallopian tube with a special reference to the p53 signature.

OBJECTIVES: Age-related changes in the expression of hormonal receptors have not been well examined in the fallopian tube (FT). We herein report the effect of menopause on the hormone receptors in ampullae of the FTs (AFTs), in comparison with cortical inclusion cysts (CICs) of the ovary. METHODS: A total of 84 AFTs and 16 fimbriae of FTs, which were obtained from 26 premenopausal and 58 postmenopausal women; and 27 postmenopausal CICs were immunohistochemically studied for the expression of p53, Ki-67, estrogen receptor-alpha (ER-α), and progesterone receptor A (PRA). Apoptotic cells were identified using a TUNEL assay. RESULTS: Postmenopausal AFTs showed a significantly lower labeling index (LI) for Ki-67 (P<0.001), apoptosis (P=0.03), and PRA (P<0.001) than premenopausal AFTs. No significant correlation with immunohistochemical markers was found in premenopausal AFTs, but the LI for PRA was positively correlated with that for Ki-67 (P=0.004) and inversely with that for p53 (P=0.023) in postmenopausal AFTs. The expression of immunohistochemical markers was closely correlated between ampullae and fimbriae of the FT. The p53 signature (p53S) was detected in five postmenopausal AFTs (mean age: 70.2 years) and was not detected in any CICs. The immunohistochemical profile of p53S was low expression of Ki-67, apoptosis, and PRA, and high expression of ER-α. The expression of PRA in CICs was significantly higher than that in AFTs (P=0.001). CONCLUSION: The expression of PRA was significantly lower in postmenopausal AFTs than in premenopausal AFTs, whereas the expression of PRA was well preserved in postmenopausal CICs.

Novel technique for adhesion barrier insertion by using cut-off surgical glove fingers in laparoscopic surgery.

AIM: Laparoscopic surgery causes fewer postoperative adhesions than laparotomy and adhesion barriers are used to lessen the chance of adhesion. Sodium hyaluronate and carboxymethylcellulose (SH-CMC), a bioresorbable membrane, is effective in preventing adhesions. However, its properties make it difficult to insert the film into the abdominal cavity and to place it into the target area during laparoscopic surgeries. Here we report a novel technique for applying SH-CMC during laparoscopic surgeries by using cut-off surgical glove fingers. METHODS: In our dry-box experiment, we found that SH-CMC became more flexible after moisturizing for 30 s. Therefore, for this procedure, we moisturizing both sides of the SH-CMC sheet (7.35 × 6.35 cm) on wet gauze (for 30 s). The film was rolled into cut-off surgical glove fingers and inserted into the abdominal cavity through a 12-mm trocar. The film was then removed from the glove finger and unrolled onto the target area (glove-finger method). RESULTS: The dry-box experiment revealed that moisturizing both sides of SH-CMC for 30 s/side, 15 min after package removal, made the film more flexible. Ninety of 96 attempts with SH-CMC were successful among the 24 patients who underwent total laparoscopic hysterectomy with our glove-finger method. CONCLUSION: Our glove-finger method can realize the smooth application of SH-CMC to the target area during laparoscopic surgeries.

BK-UM in patients with recurrent ovarian cancer or peritoneal cancer: a first-in-human phase-I study.

BACKGROUND: BK-UM (CRM197) is a mutant form of diphtheria toxin and a specific inhibitor of heparin-binding epidermal growth factor-like growth factor (HB-EGF). We assessed the safety, pharmacokinetics, recommended dose, and efficacy of BK-UM in patients with recurrent ovarian cancer (OC) or peritoneal cancer (PC), and measured HB-EGF levels in serum and abdominal fluid after BK-UM administration. METHODS: Eleven patients with advanced or recurrent OC or PC were enrolled and treated with BK-UM via the intraperitoneal route. The dose was escalated (1.0, 2.0, 3.3, and 5.0 mg/m2) using a 3 + 3 design. RESULTS: Eight of 11 patients completed treatment. No dose-limiting toxicity (DLT) was experienced at dose levels 1 (1.0 mg/m2) and 2 (2.0 mg/m2). Grade 3 transient hypotension as an adverse event (defined as a DLT in the present study) was observed in two of four patients at dose level 3 (3.3 mg/m2). Treatment with BK-UM was associated with decreases in HB-EGF levels in serum and abdominal fluid in seven of 11 patients and five of eight patients, respectively. Clinical outcomes included a partial response in one patient, stable disease in five patients, and progressive disease in five patients. CONCLUSIONS: BK-UM was well tolerated at doses of 1.0 and 2.0 mg/m2, with evidence for clinical efficacy in patients with recurrent OC or PC. A dose of 2.0 mg/m2 BK-UM is recommended for subsequent clinical trials. TRIAL REGISTRATION: This trial was prospectively performed as an investigator-initiated clinical trial. The trial numbers are UMIN000001002 and UMIN000001001, with registration dates of 1/30/2008 and 2/4/2008, respectively. UMIN000001001 was registered as a trial for the continuous administration of BK-UM after UMIN000001002 .

Clinical statistics of gynecologic cancers in Japan.

Cervical, endometrial, and ovarian cancers, have both high morbidity and mortality among the gynecologic malignant tumors in Japan. The present study was conducted using both the population-based cancer registry and the gynecologic cancer registry to elucidate the characteristics of gynecologic malignant tumors in Japan. Based on nationwide estimates from the population-based cancer registry in Japan, the morbidities and mortality of cervical, endometrial, and ovarian cancers were obtained and used for analysis. Clinicopathologic factors for cervical cancer, endometrial cancer, ovarian cancer, including age, clinical stage, postsurgical stage, histological type, therapeutic strategy, and prognosis were retrieved from the gynecologic cancer registry published by the Japan Society of Obstetrics and Gynecology and used for analysis. The morbidities of cervical, endometrial, and ovarian cancers were 10,908, 13,606, and 9,384 women in 2012, respectively. The prevalence of endometrial cancer has significantly and consistently been increasing and represents the most common gynecologic malignant tumor in Japan. The mortalities of cervical, endometrial, and ovarian cancers were 2.1, 1.3, and 3.2 per 100,000 in 2012, respectively. In 2014, 52.2% of cervical cancer patients were classified as stage I, 22.5% as stage II, 10.2% as stage III, and 11.2% as stage IV. In addition, 71.9% of endometrial cancer patients were classified as stage I, 6.0% as stage II, 13.3% as stage III, and 7.5% as stage IV. Finally, 43.2% of ovarian cancer patients were classified as stage I, 9.1% as stage II, 27.6% as stage III, and 7.2% as stage IV. Twelve-point six percent of ovarian cancer patients received neoadjuvant chemotherapy.

How to reduce the operative time of laparoscopic sacrocolpopexy?

OBJECTIVE: Laparoscopic sacrocolpopexy (LSC) has been reported to achieve lower recurrence rates, shorter recovery time, and less dyspareunia. However, as a pelvic organ prolapse (POP) surgery, LSC is problematic because it requires specific techniques and it takes a comparatively longer operative time. In this study, we present our surgical techniques of LSC and their effectiveness for shortening operative times and raising safety. METHODS: Thirty-four women with stage 2 or greater POP who underwent LSC in our hospital between September 2014 and October 2015 were enrolled in this study. The notable points of our operative procedures are as follows: (1) fixing the sigmoid colon to the left lateral abdominal wall for a clearer visualization of the sacral promontory, (2) making a retroperitoneal tunnel (not opening the peritoneum) from the sacral promontory to the Douglas pouch, (3) dissection of the vaginal wall after transvaginal hydrodissection, (4) fixation of mesh to the vaginal wall by using absorbable tacks, and (5) limiting usage of posterior mesh for the patients with posterior vaginal wall descent. RESULTS: The median operative time was 140 (range, 90-255) minutes, and blood loss was 50 (range, 10-1600) mL. The operative time decreased as the surgical techniques improved through experience. No major intra- or postoperative complications occurred. The mean follow-up period was 4 (range, 1 -14) months, and only one patient presented a recurrent grade 2 cystocele. CONCLUSION: Our unique procedures will help shorten operative times and reduce complications of LSC.

Lovastatin induced Kruppel like factor 2 (KLF2), Kruppel like factor 6 (KLF6) and Ras homolog family member B (RHOB) genes and preferentially led to viability reduction of Cisplatin-resistant cells.

It was reported that statins, inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase that are used to prevent hypercholesterolemia, have antitumor activity in several cancers. In this study, we investigated the cell viability of statins in Cisplatin-resistant HCP4 and PCDP5 cells compared with their parent Hela and PC3 cells, respectively, and found that HCP4 and PCDP5 cells were 37-fold and 18-fold more resistant to Cisplatin but 13-fold and 7-fold more sensitive to Lovastatin by cell proliferation assay. Lovastatin induced the apoptosis of HCP4 cells more rapidly and to greater extent than in Hela cells as assessed by flow cytometry and western blotting analyses. The MVA pathway was not involved in this acquired Cisplatin resistance. To elucidate the mechanism underlying the reduced viability to Lovastatin, we performed cDNA microarray analysis and identified 65 and 54 genes that were induced more than 2-fold by Lovastatin in HCP4 and PCDP5 cells, respectively. Of these, only three genes, KLF2, KLF6, and RHOB, were commonly induced between HCP4 and PCDP5 cells. These mRNAs were strongly induced by Lovastatin with transcriptional regulation in HCP4 cells. Consistent with transcription, the protein expression of RHOB also was induced by Lovastatin. The induction of these genes was associated with cell cycle arrest and apoptosis. Combination treatment with Cisplatin and Lovastatin resulted in an agonistic effect in Hela and PC3 cells and an antagonistic effect in HCP4 and PCDP5 cells. These results suggest that statins might have the potential to overcome Cisplatin resistance as single-agent therapy.