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To develop a new therapeutic strategy for taxane/platinum-resistant/refractory ovarian and primary peritoneal cancers, we evaluated the feasibility and efficacy of irinotecan and gemcitabine combination chemotherapy.Patients with taxane/platinum-resistant/refractory cancer received escalating doses of irinotecan and gemcitabine (level 1: 80 and 800 mg/mA total of 35 patients were enrolled. The recommended dose was defined as 100 mg/mCombination chemotherapy with irinotecan and gemcitabine represents a safe and effective treatment combination for taxane/platinum-resistant/refractory ovarian and primary peritoneal cancers.

Background In Japan, the cervical cancer preventative HPV vaccination rate has dramatically declined, directly as a result of repeated broadcasts of so-called adverse events and the resulting suspension of the government’s recommendation. Our previous survey of obstetricians and gynecologists in Japan regarding their opinions toward HPV vaccination revealed that these key specialists were as negatively influenced by the reports of purported negative events as were the general population. Here, we report a 3-year follow-up survey of these clinicians. Methods We reused the same questionnaire format as used in our 2014 survey, but added new questions concerning opinions regarding a WHO statement and reports of a Japanese nation-wide epidemiological study related to the adverse events, released in 2015 and 2016, respectively. Results The response rate was 46% (259/567): 5 (16.1%) of 31 doctors had inoculated their own teenaged daughters during the time period since the previous survey, despite the continued suspension of the governmental recommendation, whereas in the previous survey none of the doctors had done so. Among the respondents, the majority claimed awareness of the recent pro-vaccine WHO statement (66.5%), and of the report of a Japanese epidemiological study (71.5%), and a majority affirmed they currently held positive opinions of the safety (72.7%) and effectiveness (84.3%) of the HPV vaccine. Conclusions Our re-survey of Japan’s obstetricians and gynecologists regarding their opinions about the HPV vaccine found that their opinions have changed, potentially leading to a more positive future re-engagement for HPV vaccination in Japan.

Improved surgical techniques and immunosuppressant medications for organ transplantation have resulted in a significant increase in the number of women undergoing renal transplantation. Peritoneal dialysis (PD), a common supportive therapy for chronic renal failure, is also used in cases of renal transplantation failure. Herein, we report the first case of a rare total conventional laparoscopic gynecologic hysterectomy performed for endometrial cancer in a patient undergoing life-supportive PD as a result of renal transplantation failure. No unusual intraoperative complications were experienced, but post-surgical peritoneal leakage was observed. We reviewed the literature of alternative surgical methods of hysterectomy for endometrial cancer in patients who had undergone renal transplantation and were undergoing PD at the time of the hysterectomy. Laparoscopic hysterectomy could be safe in a renal transplantation patient receiving PD if injury to the transplanted ureter and renal artery is avoided by recognizing the patient's anatomy and PD leakage is averted by careful peritoneum suture and avoiding contact with the PD catheter.

Background Sheehan’s syndrome occurs because of severe postpartum hemorrhage causing ischemic pituitary necrosis. Sheehan’s syndrome is a well-known condition that is generally diagnosed several years postpartum. However, acute Sheehan’s syndrome is rare, and clinicians have little exposure to it. It can be life-threatening. There have been no reviews of acute Sheehan’s syndrome and no reports of successful pregnancies after acute Sheehan’s syndrome. We present such a case, and to understand this rare condition, we have reviewed and discussed the literature pertaining to it. An electronic search for acute Sheehan’s syndrome in the literature from January 1990 and May 2014 was performed. Case presentation A 27-year-old woman had massive postpartum hemorrhage (approximately 5000 mL) at her first delivery due to atonic bleeding. She was transfused and treated with uterine embolization, which successfully stopped the bleeding. The postpartum period was uncomplicated through day 7 following the hemorrhage. However, on day 8, the patient had sudden onset of seizures and subsequently became comatose. Laboratory results revealed hypothyroidism, hypoglycemia, hypoprolactinemia, and adrenal insufficiency. Thus, the patient was diagnosed with acute Sheehan’s syndrome. Following treatment with thyroxine and hydrocortisone, her condition improved, and she was discharged on day 24. Her next pregnancy was established 2 years after her first delivery. She required induction of ovulation for the next conception. The pregnancy, delivery, and postpartum period were uneventful. An electronic search of the literature yielded 21 cases of acute Sheehan’s syndrome. Presenting signs varied, including adrenal insufficiency (12 cases), diabetes insipidus (4 cases), hypothyroidism (2 cases), and panhypopituitarism (3 cases), with a median time of presentation after delivery for each of those conditions being 7.9, 4, 18, and 9 days, respectively. Serial changes in magnetic resonance imaging were reported in some cases of acute Sheehan’s syndrome. Conclusion Clinicians should be aware of the risk of acute Sheehan’s syndrome after a massive postpartum hemorrhage in order to diagnose it accurately and treat it promptly.

The use of smartphones, mobile networks and associated health applications (known as apps) is now almost universal. Countries with low medical resources need assistance in their delivery of healthcare. This is particularly true where there are limited numbers of specialised physicians or nurses with respect to cancer screening. As smartphones become more universal, real-time and near-real-time expert medical consultations and telediagnosis are becoming more common. This leads us to believe that there will soon be a demand for mobile cancer screening services, which will be particularly useful for women living in rural areas or doctor-less inner city communities. The smartphone would seem to have almost limitless possibilities to address this need. As a first step in studying how cervical cancer screening using a smartphone could have widespread implementation, we conducted a pilot study to evaluate the utility of a smartphone to diagnose cervical intraepithelial neoplasm or invasive cervical cancer in 20 patients having an abnormal cervical cytology. Our results indicate that continuing progress in digital imaging devices may allow the quality of cervical cancer screening to be improved.

Objective: In Japan, the possible adverse events upon HPV vaccination was widely reported in the media. MHLW announced the suspension of aggressively encouraging HPV vaccination in 2013, and inoculation rate has sharply declined. The aim of the present study was estimation of future cervical cancer risk. Methods: The latest data on vaccination rate at each age in Sakai City were first investigated. The rate of experiencing sexual intercourse at the age of 12, 13, 14, 15, 16, 17 and throughout lifetime is assumed to be 0%, 1%, 2%, 5%, 15%, 25%, and 85% respectively. The cervical cancer risk was regarded to be proportional to the relative risk of HPV infection over the lifetime. The risk in those born in 1993 whom HPV vaccination was not available yet for was defined to be 1.0000. Results: The cumulative vaccination rates were 65.8% in those born in 1994, 72.7% in 1995, 72.8% in 1996, 75.7% in 1997, 75.0% in 1998, 66.8% in 1999, 4.1% in 2000, 1.5% in 2001, 0.1% in 2002, and 0.1% in 2003. The relative cervical cancer risk in those born in 1994–1999 was reduced to 0.56–0.70, however, the rate in those born in 2000–2003 was 0.98–1.0, almost the same risk as before introduction of the vaccine. Discussion: The cumulative initial vaccination rates were different by the year of birth. It is confirmed that the risk of future cervical cancer differs in accordance with the year of birth. For these females, cervical cancer screening should be recommended more strongly.

Microscopic examination of urine sediment is a basic, common method of detecting diseases of the urinary tract. We experienced a case involving a patient who had developed a fever after undergoing a urinary-diversion operation. Results of the microscopic examination of the urine collected from the urostomy pouch of the patient showed a food debris-like component. Based on this finding, we suspected a fistula between the urinary and intestinal tracts. However, after performing an experiment to verify the results, we determined that no fistula was present. Instead, we discovered that the food debris-like component originated from the urostomy skin barrier. To our knowledge, ours is the first report in the literature to demonstrate that the urostomy skin barrier can dissolve and mimic food debris in urine sediment, leading to incorrect assumptions regarding the presence of fistulas. We believe that it is important to derive a correct diagnosis when an unfamiliar component is observed in urinary sediment. We further believe that the findings from this case are valuable to professionals who administer clinical treatment and perform laboratory testing.

The purpose of this study is to evaluate dose–volume histogram (DVH) predictors for the development of chronic gastrointestinal (GI) complications in patients with cervical cancer who have undergone postoperative concurrent chemotherapy and whole-pelvic radiation therapy (WPRT). The subjects were 135 patients who had undergone postoperative WPRT with concurrent nedaplatin-based chemotherapy between 2000 and 2014. Associations between selected DVH parameters and the incidence of chronic GI complications of G3 or higher were evaluated. Chronic GI complications of severity G3 occurred in 18 (13%) patients. Patients with GI complications had significantly greater V5–V45, mean dose and the generalized equivalent uniform dose (gEUD) of the small bowel loops, compared with those without GI complications. V30–V45, mean dose and gEUD of the bowel bag also showed significant differences between patients with and without GI complications. In contrast, no parameter for the large bowel loop was correlated with GI complications. Receiver operating characteristics curve analysis indicated that V30–V45 of the small bowel loops were better predictors than these respective parameters for the bowel bag. Next, patients were divided into four groups based on the median V15 and V40 of the small bowel loops. The group with both a high V15 and a high V40 showed a significantly higher probability of chronic GI complications. In conclusion, the small bowel loops are better predictors of chronic GI complications compared with the bowel bag, and a relatively high-dose volume (e.g. V40) of the small bowel loops is a useful predictor of chronic GI complications.

Multidrug resistance is a major concern in uterine leiomyosarcoma treatment. Development of effective chemotherapies and management of drug resistance in patients is necessary. The copper efflux transporter adenosine triphosphatase copper transporting beta is a member of the P-type adenosine triphosphatase family and is also known as a strong platinum efflux transporter. Various reports have shown the association between adenosine triphosphatase copper transporting beta and platinum resistance; however, suitable inhibitors or methods for inhibiting platinum efflux via adenosine triphosphatase copper transporting beta are not developed.Our study focused on platinum resistance in uterine leiomyosarcoma. The role of adenosine triphosphatase copper transporting beta in uterine leiomyosarcoma resistance to platinum drugs was investigated both in vitro and in vivo.Adenosine triphosphatase copper transporting beta expression was investigated by Western blotting and the efficacy of copper sulfate pretreatment and cisplatin administration in adenosine triphosphatase copper transporting beta-expressing cells was investigated both in vitro and in vivo.Western blot analysis of SK-LMS-1 cells (uterine leiomyosarcoma cell line) revealed strong adenosine triphosphatase copper transporting beta expression. A permanent SK-LMS-ATPase copper transporting beta-suppressed cell line (SK-LMS-7B cells) was generated, and cisplatin exhibited a significant antitumor effect in SK-LMS-7B cells, both in vitro (SK-LMS-1 cells, half-maximal inhibitory concentration, 17.2 μM; SK-LMS-7B cells, half-maximal inhibitory concentration, 4.2 μM, P.01) and in xenografts compared with that in SK-LMS-1 cells (5.8% vs 62.8%, P.01). Copper sulfate was identified as a preferential inhibitor of platinum efflux via adenosine triphosphatase copper transporting beta. In SK-LMS-1 cells pretreated with 15 μM copper sulfate for 3 hours, the cisplatin half-maximal inhibitory concentration decreased significantly compared with that in untreated cells and resulted in significantly increased intracellular platinum accumulation (1.9 pg/cell vs 8.6 pg/cell, P.01). The combination of copper sulfate pretreatment with cisplatin administration was also effective in vivo and caused cisplatin to exhibit significantly increased antitumor effects in mice with SK-LMS-1 xenografts (3.1% vs 62.7%, P.01).Our study demonstrates that adenosine triphosphatase copper transporting beta is overexpressed in uterine leiomyosarcoma cells and that copper sulfate, which acts as an inhibitor of platinum efflux via adenosine triphosphatase copper transporting beta, may be a therapeutic agent in the treatment of uterine leiomyosarcoma.

To compare the efficacy, safety, and tolerability profiles of pegylated liposomal doxorubicin and carboplatin (PLDC) with those of gemcitabine and carboplatin (GC) for the treatment of patients with platinum-sensitive recurrent ovarian cancer. Ovarian cancer patients with recurrence > 6 months after first-line platinum and taxane-based therapies were randomly assigned to PLDC [pegylated liposomal doxorubicin 30 mg/m2 plus carboplatin area under the curve (AUC) 5 mg/mL/min on day 1] every 4 weeks or GC (gemcitabine 1000 mg/m2 on days 1 and 8 plus carboplatin AUC 4 mg/mL/min on day 1) every 3 weeks for at least 6 cycles. The primary endpoint was progression-free survival, and overall response rate, overall survival, toxicity, and dose administration were secondary endpoints. One-hundred patients (49 PLDC; 51 GC) were randomly assigned. Over a median follow-up of 24 months, the median progression-free survival was 12.0 months (95% CI 9.2–15.0) for PLDC and 9.8 months (8.9–12.3) for GC [HR 0.69 (0.455–1.047)] with a difference of 2.2 months. The response rate was 57.1% (41.0–72.3) for PLDC and 56.4% (39.6–72.2) for GC. No obvious differences in toxicity (G3/4) were noted between arms. The median relative dose intensity of planned dose per week was 88.9% for pegylated liposomal doxorubicin and 53.1% for gemcitabine (p

The median eminence (ME) anatomically consists of external (eME) and internal (iME) layers. The hypothalamic neurosecretory cells terminate their axons in the eME and secrete their neurohormones regulating anterior pituitary hormone secretion involved in stress responses into the portal vein located in the eME. Magnocellular neurosecretory cells (MNCs) which produce arginine vasopressin (AVP) and oxytocin in the paraventricular (PVN) and supraoptic nuclei (SON) terminate their axons in the posterior pituitary gland (PP) through the iME. Here, we provide the first evidence that oestrogen modulates the dynamic changes in AVP levels in the eME axon terminals in female rats, using AVP-eGFP and AVP-DREADDs transgenic rats. Strong AVP-eGFP fluorescence in the eME was observed at all oestrus cycle stages in adult female rats but not in male transgenic rats. AVP-eGFP fluorescence in the eME was depleted after bilateral ovariectomy but re-appeared with high-dose 17β-oestradiol. AVP-eGFP fluorescence in the MNCs and PP did not change significantly in most treatments. Peripheral clozapine-N-oxide administration induced AVP-DREADDs neurone activation, causing a significant increase in plasma corticosterone levels in the transgenic rats. These results suggest that stress-induced activation of the hypothalamic-pituitary-adrenal axis may be caused by oestrogen-dependent upregulation of AVP in the eME of female rats.

The incidence and long-term survival analysis for vulvar cancer, due to its rarity, has not been fully described in Asian population. The objective of the study is to determine the trends in incidence and long-term survival for vulvar cancer in a Japanese population, using a population-based cancer registry data in Osaka, Japan. The age-standardized incidence rate of 389 cases of vulvar squamous cell carcinoma (SCC) diagnosed between 1976 and 2010 was calculated, using the 1985 model population of Japan. The annual percentage change (APC) of the age-standardized incidence was estimated by the joinpoint regression models. The 5- and 10-year relative survival of 290 cases with vulvar SCC diagnosed between 1976 and 2008 were analyzed, using a cohort or period approach. Using the 10-year relative survival, the conditional 5-year survival for patients who lived for some years after diagnosis was also calculated. We have found that the age-standardized incidence rate for vulvar cancer trended downward during the period of 1979–1992 (APC − 6.3%; 95% confidence interval (CI) [− 11.3% to − 1.0%]), whereas it trended upward from 1993 to 2010 (APC 1.9%; 95% CI [− 0.7% to 4.6%]). There was no statistically significant difference for the 5- and 10-year relative survival between the two periods of 1976–2000 and 2001–2008. A statistically significant increase in the conditional 5-year survival at 2 years after diagnosis was observed (48.4%; 95% CI [41.1–55.3] versus 75.6%; 95% CI [64.0–83.9]). Despite an increasing trend in vulvar cancer incidence among Japanese population, the relative survival rate for vulvar cancer did not change over the 35 years of this study. We found that the conditional 5-year survival for vulvar cancer, as patients survived additional years, approached within reach of 100%. These data can provide valuable information for both patients and clinicians.

Radical hysterectomy is the currently accepted treatment for early-stage cervical cancer. Various radical hysterectomy techniques have been demonstrated in the literature, based predominantly around abdominal radical hysterectomy but more recently on laparoscopic radical hysterectomy. Over the last two decades, many studies have indicated laparoscopic radical hysterectomy’s safety and feasibility for early-stage cervical cancer. The proven benefits, in the appropriately selected cancer patient, of laparoscopy over laparotomy for radical hysterectomy have been significant reductions in blood loss, pain, duration of hospital stay, wound complications, etc. However, until just recently, there had been few studies comparing laparoscopic radical hysterectomy and abdominal radical hysterectomy regarding recurrence and survival rates over a long follow-up period. In this chapter, we review previous reports of laparoscopic radical hysterectomy, having relatively large number of patients, that described perioperative morbidity, tumor recurrence, and survival rate. We present our view of laparoscopic radical hysterectomy’s bright prospects for the future.

This study aimed to determine the association between umbilical cord leucine-rich alpha-2 glycoprotein (LRG) and fetal infection and investigate the underlying mechanism of LRG elevation in fetuses. We retrospectively reviewed the medical records of patients who delivered at Osaka University Hospital between 2012 and 2017 and selected those with histologically confirmed chorioamnionitis (CAM), which is a common pregnancy complication that may cause neonatal infection. The participants were divided into two groups: CAM with fetal infection (CAM-f[+] group,n =14) and CAM without fetal infection (CAM-f[−] group,n =31). Fetal infection was defined by the histological evidence of funisitis. We also selected 50 cases without clinical signs of CAM to serve as the control. LRG concentrations in sera obtained from the umbilical cord were unaffected by gestational age at delivery, neonatal birth weight, nor the presence of noninfectious obstetric complications (all,p> 0.05). Meanwhile, the LRG levels (median, Interquartile range [IQR]) were significantly higher in the CAM-f(+) group (10.37 [5.21–13.7] μg/ml) than in the CAM-f(−) (3.61 [2.71–4.65] μg/ml) or control group (3.39 [2.81–3.93] μg/ml;p< 0.01). The area under the receiver operating characteristic (ROC) curve of LRG for recognizing fetal infection was 0.92 (optimal cutoff, 5.08 μg/ml; sensitivity, 86%; specificity, 88%). In a mouse CAM model established by lipopolysaccharide administration, the fetal LRG protein in sera andLRGmRNA in the liver were significantly higher than those in phosphate-buffered saline (PBS)-administered control mice (p< 0.01).In vitroexperiments using a fetal liver-derived cell line (WRL68) showed that the expression ofLRGmRNA was significantly increased after interleukin (IL)-6, IL-1β, and tumor necrosis factor- alpha (TNF-α) stimulation (p< 0.01); the induction was considerably stronger following IL-6 and TNF-α stimulation (p< 0.01). In conclusion, LRG is an effective biomarker of fetal infection, and fetal hepatocytes stimulated with inflammatory cytokines may be the primary source of LRG productionin utero.

Aim In Japan, the rate of routine cervical cancer screening is quite low, and the incidence of cervical cancer has recently been increasing. Our objective was to investigate ways to effectively influence parental willingness to recommend that their 20-year-old daughters undergo cervical cancer screening. Methods We targeted parents whose 20-year-old daughters were living with them. In fiscal year 2013, as usual, the daughter received a reminder postcard several months after they had received a free coupon for cervical cancer screening. In fiscal year 2014, the targeted parents received a cervical cancer information leaflet, as well as a cartoon about cervical cancer to show to their daughters, with a request that they recommend to their daughter that she undergo cervical cancer screening. The subsequent screening rates for fiscal years 2013 and 2014 were compared. Results The cervical cancer screening rate of 20-year-old women whose parents received the information packet in fiscal year 2014 was significantly higher than for the women who, in fiscal year 2013, received only a simple reminder postcard (P < 0.001). As a result, the total screening rate for 20-year-old women for the whole of the 2014 fiscal year was significantly increased over 2013 (P < 0.001). Conclusion For the first time, we have shown that the parents of 20-year-old daughters can be motivated to recommend that their daughters receive their first cervical cancer screening. This was achieved by sending a cervical cancer information leaflet and a cartoon about cervical cancer for these parents to show to their daughters. This method was significantly effective for improving cervical cancer screening rates.

An advanced sterilization system employing active oxygen species (AOS) was investigated. We revealed in a previous paper that, by using active oxygen species generated from oxygen gas by ultraviolet irradiation in the chamber of the sterilization system, the survival curves of Geobacillus stearothermophilus spores (10 6 CFU), a biological indicator (BI), showed exponential reduction, and that this sterilization was attributable to the UV-generated AOS. However, we had little knowledge of what specific types of AOS were primarily responsible for the sterilization effects. Therefore, in this study we investigated the principal sterilization contributors among the AOS generated by ultraviolet irradiation, using the electron spin resonance (ESR) technique, with 2,2,6,6-tetramethyl-4-piperidinol (TEMP) as a spin-label reagent for the excited state of atomic oxygen molecules ( 1 O 2 ), and compared the respective sterilization effects of AOS and oxygen plasma system.

To examine the effect of the histology of carcinoma and sarcoma components on survival outcome of uterine carcinosarcoma.A multicenter retrospective study was conducted to examine uterine carcinosarcoma cases that underwent primary surgical staging. Archived slides were examined and histologic patterns were grouped based on carcinoma (low-grade versus high-grade) and sarcoma (homologous versus heterologous) components, correlating to clinico-pathological demographics and outcomes.Among 1192 cases identified, 906 cases were evaluated for histologic patterns (carcinoma/sarcoma) with high-grade/homologous (40.8%) being the most common type followed by high-grade/heterologous (30.9%), low-grade/homologous (18.0%), and low-grade/heterologous (10.3%). On multivariate analysis, high-grade/heterologous (5-year rate, 34.0%, P = 0.024) and high-grade/homologous (45.8%, P = 0.017) but not low-grade/heterologous (50.6%, P = 0.089) were independently associated with decreased progression-free survival (PFS) compared with low-grade/homologous (60.3%). In addition, older age, residual disease at surgery, large tumor, sarcoma dominance, deep myometrial invasion, lymphovascular space invasion, and advanced-stage disease were independently associated with decreased PFS (all, P0.01). Both postoperative chemotherapy (5-year rates, 48.6% versus 39.0%, P0.001) and radiotherapy (50.1% versus 44.1%, P = 0.007) were significantly associated with improved PFS in univariate analysis. However, on multivariate analysis, only postoperative chemotherapy remained an independent predictor for improved PFS [hazard ratio (HR) 0.34, 95% confidence interval (CI) 0.27-0.43, P0.001]. On univariate analysis, significant treatment benefits for PFS were seen with ifosfamide for low-grade carcinoma (82.0% versus 49.8%, P = 0.001), platinum for high-grade carcinoma (46.9% versus 32.4%, P = 0.034) and homologous sarcoma (53.1% versus 38.2%, P = 0.017), and anthracycline for heterologous sarcoma (66.2% versus 39.3%, P = 0.005). Conversely, platinum, taxane, and anthracycline for low-grade carcinoma, and anthracycline for homologous sarcoma had no effect on PFS compared with non-chemotherapy group (all, P0.05). On multivariate analysis, ifosfamide for low-grade/homologous (HR 0.21, 95% CI 0.07-0.63, P = 0.005), platinum for high-grade/homologous (HR 0.36, 95% CI 0.22-0.60, P0.001), and anthracycline for high-grade/heterologous (HR 0.30, 95% CI 0.14-0.62, P = 0.001) remained independent predictors for improved PFS. Analyses of 1096 metastatic sites showed that carcinoma components tended to spread lymphatically, while sarcoma components tended to spread loco-regionally (P0.001).Characterization of histologic pattern provides valuable information in the management of uterine carcinosarcoma.

Transcriptional coactivator with PDZ-binding motif (TAZ) is a crucial component of the Hippo tumor suppressor pathway, interacting with transcriptional factors to regulate cell proliferation, apoptosis and tumorigenesis. TAZ and its paralog, Yes-associated protein (YAP), are activated at high frequencies during the progression towards malignancy in various tumors. Recently, YAP has been identified to modulate oncogenic features in endometrial adenocarcinoma, and it has also been reported that the nuclear expression of YAP is correlated with the poorly-differentiated form of endometrioid adenocarcinoma. In contrast to YAP, no studies have investigated TAZ expression in endometrioid adenocarcinoma. In the present study, TAZ expression was immunohistochemically examined in 55 clinical samples of endometrioid adenocarcinoma, and the clinical implications were evaluated. The results demonstrated that TAZ was located primarily in the cell nuclei, and that high TAZ expression was significantly correlated with high tumor-factor (P=0.024), stage (P=0.041) and histological grade (P=0.001), lymph node metastasis (P=0.046), recurrence (P=0.002) and a poor prognosis (P=0.007). Furthermore, univariate analysis identified that high TAZ expression was a poor prognostic factor for overall and disease-free survival. To the best of our knowledge, the present case is the first to report the clinical implications of TAZ in endometrioid adenocarcinoma of the uterus. TAZ may become a marker of a poor prognosis in endometrioid adenocarcinoma.

Several molecular targeting drugs are being evaluated for endometrial cancer; selecting patients whose cancers are sensitive to these agents is of paramount importance. Previously, we developed the cancer tissue-originated spheroid method for primary cancer cells taken from patients' tumors as well as patient-derived xenografts. In this study, we successfully prepared and cultured cancer tissue-originated spheroids from endometrial cancers. Characteristics of the original tumors were well retained in cancer tissue-originated spheroids including morphology and expression of p53 or neuroendocrine markers. We screened 79 molecular targeting drugs using two cancer tissue-originated spheroid lines derived from endometrioid adenocarcinoma grade 3 and serous adenocarcinoma. Among several hits, we focused on everolimus, a mammalian target of rapamycin complex 1 inhibitor, and YM155, a survivin inhibitor. When sensitivity to everolimus or YM155 was assessed in 12 or 11 cancer tissue-originated spheroids, respectively, from different endometrial cancer patients, the sensitivity varied substantially. The cancer tissue-originated spheroids sensitive to everolimus showed remarkable suppression of proliferation. The phosphorylation status of the mammalian target of rapamycin complex 1 downstream molecules before and after everolimus treatment did not predict the effect of the drug. In contrast, the cancer tissue-originated spheroids sensitive to YM155 showed remarkable cell death. The effect of YM155 was also confirmed in vivo. The histological type correlated with YM155 sensitivity; non-endometrioid adenocarcinomas were sensitive and endometrioid adenocarcinomas were resistant. Non-canonical autophagic cell death was the most likely cause of cell death in a sensitive cancer tissue-originated spheroid. Thus, sensitivity assays using cancer tissue-originated spheroids from endometrial cancers may be useful for screening drugs and finding biomarkers.

Background/Aims: The study aims to prevent serious urologic injury during a radical hysterectomy; we propose that one of the most important procedural steps is the careful management of the vesicouterine ligament (VUL). Patients and Methods: Between January 2013 and October 2014, we used a novel internal retractor in 17 patients undergoing a laparoscopic radical hysterectomy (LRH) for early-stage cervical cancer to obtain and secure a better surgical view. For management of the VUL during the laparoscopic procedure, we routinely used an internal retractor (EndoGrab; Virtual Ports, Misgav, Israel) and vessel tape to reposition the ureter in a safe lateral-caudal direction. Results: Using an EndoGrab, we were easily able to reproduce a suitable surgical view that simulated the one obtained by an abdominal route for radical hysterectomy. Using this improved laparoscopic procedure, we completed radical hysterectomies in all 17 cases without a ureteral injury complication. Conclusion: Our modified method using an EndoGrab is effective for the prevention of ureteral injury during a LRH, and its ease of use makes it suitable even for those surgeons early in their laparoscopic learning curve.

The objective of this study is to analyze the clinical outcomes of abnormal cervical cytology and newly diagnosed human papillomavirus (HPV)-related disease after organ transplantation. Medical records from July 2004 to August 2015 were reviewed, and thirteen patients were identified who had been newly diagnosed with HPV-related disease (cervical intraepithelial neoplasia [CIN] and cervical cancer) after organ transplantation. The median transition time to the aggravation of cervical cytology and the spontaneous regression rate of CIN were evaluated. Clinical outcomes of CIN1 and CIN2 were compared between the general population and patients with organ transplantation. We also reviewed the current literature regarding the incidence of HPV infection, Pap smear abnormality and/or CIN after organ transplantation. The cervical cytology aggravated in nine of the 13 patients (69 %). In seven of the 13 cases (54 %), treatments such as cervical conization, laser vaporization, or radiation therapy, were conducted. HPV-related disease disappeared after treatment in only three of the seven actively treated cases (43 %). In contrast, the lesions persisted in three (43 %) cases after treatment. One patient died from cervical cancer. The spontaneous regression rate of the HPV-related diseases, if left untreated, was 0 %. There was a statistically significant difference in the clinical outcomes of CIN1 and CIN2 between the general population and patients with organ transplantation (p = 0.0026 and 0.0315, respectively; chi-squared test). HPV-related lesions that are newly diagnosed after organ transplantation do not seem to regress as spontaneously as in the general population. Physicians should recognize the importance of close monitoring and long-term follow-up.

The objective of this study was to investigate the predictive value of F-18-fluorodeoxyglucose positron emission tomography (FDG-PET) for early assessment of tumor response to chemotherapy and for patient survival in gynecologic malignancies. We performed CT and FDG-PET scans before initiation of chemotherapy to determine baseline conditions. PET scan was repeated after the first cycle of chemotherapy. The tumor response was later evaluated by CT scans after three cycles of chemotherapy, using RECIST. The PET response was analyzed in terms of the difference in SUVmax for FDG of the patient’s largest lesion between the baseline scan and after the first cycle of chemotherapy. The metabolic response for the tumor was defined as a 30 % reduction in its SUVmax. Eleven patients received platinum-based regimens, and 20 patients received non-platinum-based regimens. The mean progression-free survival (PFS) for the patients with a metabolic response was 13 months (range 5–29). In contrast, the mean PFS of the patients with no metabolic response was only 4.3 months (range 1–18). There was a statistically significant difference between the metabolic response and PFS (p = 0.002, Mann–Whitney U test). There was a strong correlation between the metabolic response and RECIST, regardless of the chemotherapy regimens used (platinum-based group, p = 0.006; non-platinum group, p = 0.046, Fisher’s exact test). The metabolic change in SUVmax was clearly predictive of tumor response in 93.5 % of patients. Early FDG-PET assessment by measuring the single largest lesion is a very promising tool for rapidly predicting tumor responses and patient survival, regardless of the chemotherapy regimen.

Mature cystic teratoma is a germ cell tumor of the ovaries and is often observed in clinical practice. However, extragonadal teratomas are rare tumors and have been reported outside the ovaries, (e.g., in the greater omentum). The mechanism underlying the development of extragonadal teratomas remains unknown. We encountered a case of extragonadal teratoma in the pouch of Douglas that appeared to be a parasitic dermoid cyst. From our experience and the literature review, we discuss the potential mechanism leading to the development of extragonadal teratomas. A 41-year-old nonpregnant woman was referred to our department due to myoma and anemia. A 4-cm asymptomatic mass in the pouch of Douglas was observed, and the patient was diagnosed with ovarian mature cystic teratoma. She underwent laparoscopic surgery, and intraoperative findings revealed that the fallopian tube was injured and torn, and a residual small ovary was observed in the left side of the ovary. A tumor measuring approximately 4 cm observed in the pouch of Douglas was extracted without rupturing. The tumor was diagnosed as a parasitic dermoid cyst by macroscopic and histopathological findings. Auto-amputation could be the underlying mechanism that leads to an isolated parasitic dermoid cyst in the pouch of Douglas.

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.

In Japan, the trend for cervical cancer at younger ages has been increasing. As a countermeasure, the HPV vaccine was introduced as a routine vaccination in April 2013. However, the Ministry of Health, Labour and Welfare (MHLW) announced a “Suspension of its active inoculation recommendation for HPV vaccine” in June 2013. In 2016, 32 months after that suspension, we conducted survey via Internet and compared the results with our previous ones conducted at 9 and 23 months after suspension (in 2014 and 2015, respectively). We examined the ‘time-dependent change’ of the ‘intention of mothers to inoculate their daughters with the HPV vaccine’ in terms of efficacy of external decision-making support. 17.5% of mothers in the first survey replied that they would inoculate their daughters under the current circumstances, 12.1% in the second survey, and 6.7% in the third, showing a consistent decrease in willingness over time (p = 0.03, p < 0.01). If the government recommendation were to be reintroduced, 22.5% of mothers in the first survey replied they would inoculate their daughters, 21.0% in the second survey, which indicated no significant difference (p = 0.65) over the first interval; however, this was significantly decreased to 12.2% in the third survey (p < 0.01). Our study revealed that the intention to inoculate their daughters has been declining among Japanese mothers over time triggered by the suspension.

PURPOSE: To propose a categorization model of uterine carcinosarcoma (UCS) based on tumor cell types (carcinoma and sarcoma) and sarcoma dominance. METHODS: This secondary analysis of a prior multicenter retrospective study examined 889 cases of UCS with available histologic evaluation. Based on survival outcome, cases were clustered into three groups: low-grade carcinoma with nondominant homologous sarcoma [type A, n = 96 (10.8%)], (1) low-grade carcinoma with heterologous sarcoma or any sarcoma dominance and (2) high-grade carcinoma with nondominant homologous sarcoma [type B, n = 412 (46.3%)], and high-grade carcinoma with heterologous sarcoma or any sarcoma dominance [type C, n = 381 (42.9%)]. Tumor characteristics and outcome were examined based on the categorization. RESULTS: Women in type C category were more likely to be older, obese, and Caucasian, whereas those in type A category were younger, less obese, Asian, and nulligravid (all P < 0.01). Type C tumors were more likely to have metastatic implants, large tumor size, lymphovascular space invasion with sarcoma cells, and higher lymph node ratio, whereas type A tumors were more likely to be early-stage disease and small (all P < 0.05). On multivariate analysis, tumor categorization was independently associated with progression-free survival (5-year rates: 70.1% for type A, 48.3% for type B, and 35.9% for type C, adjusted P < 0.01) and cause-specific survival (5-year rates: 82.8% for type A, 63.0% for type B, and 47.1% for type C, adjusted P < 0.01). CONCLUSION: Characteristic differences in clinicopathological factors and outcomes in UCS imply that different underlying etiologies and biological behaviors may be present, supporting a new classification system.

OBJECTIVE: To examine significance of sarcoma dominance (SD) patterns In uterine carcinosarcoma (UCS). METHODS: This is a secondary analysis of multicenter retrospective study examining women with stages I-IV UCS who underwent primary surgery. SD was defined as >50% of sarcoma component in uterine tumor. SD patterns were grouped as homologous sarcoma without SD (homo/non-dominance, n = 351), heterologous sarcoma without SD (hetero/non-dominance, n = 174), homologous sarcoma with SD (homo/dominance, n = 175), and heterologous sarcoma with SD (hetero/dominance, n = 189), and correlated to tumor characteristics and survival. RESULTS: SD patterns were significantly associated with age, body habitus, carcinoma type, tumor size, depth of myometrial invasion, and nodal metastasis (all, P < 0.05). On univariate analysis, SD was associated with decreased progression-free survival (PFS) and cause-specific survival (CSS) in homologous cases (both, P < 0.05) but not in heterologous cases. On multivariate models, both homologous and heterologous SD patterns remained independent prognostic factors for decreased PFS (adjusted-hazard ratio [HR] ranges: homo/dominance 1.35–1.69, and hetero/dominance 1.47–1.64) and CSS (adjusted-HR ranges: 1.52–1.84 and 1.66–1.81, respectively) compared to homo/non-dominance (all, P < 0.05). Among stage I-III disease, when tumors had SD, adding radiotherapy to chemotherapy was significantly associated with improved PFS (adjusted-HR: homo/dominance 0.49, and hetero/dominance 0.45) and CSS (0.36 and 0.31, respectively) compared to chemotherapy alone (all, P < 0.05); contrary, this association was not observed with absence of SD (all, P > 0.05). CONCLUSION: In UCS, SD impacts survival in homologous but not in heterologous type. Regardless of sarcoma types, SD was associated with decreased survival in UCS; adding radiotherapy to chemotherapy may be an effective postoperative strategy.

Background Placenta percreta is a rare obstetric condition associated with the risk of massive intraoperative hemorrhage. Recently, conservative management of placenta percreta has been performed to reduce maternal morbidity. However, various complications have been reported during such management. Only a few cases of asymptomatic disseminated intravascular coagulation (DIC) or fever without infection have been reported. Here, we discuss such a case and review the related literature to understand this rare condition better. For this, we performed an electronic literature review. Case presentation We present the clinical course, results of blood tests, and serial magnetic resonance images of a 35-year-old female (gravida 5, para 2) with placenta percreta complicated by placenta previa that was managed conservatively. The patient successfully delivered a healthy baby by a cesarean delivery via a transverse uterine fundal incision at 36 weeks of gestation. We did not observe intraoperative complications during cesarean delivery, and the postoperative course remained uncomplicated until 47 days after the delivery. However, asymptomatic DIC developed after 47 days, and her serum fibrinogen level declined to 42 mg/dL, which was successfully treated with anticoagulant therapy by a therapeutic dose of intravenous heparin for 22 days (postoperative days 48–69). Although DIC resolved, subsequent fever persisted for approximately 1 month (postoperative days 67–103). Infection was ruled out, and conservative management was successfully continued. Literature review revealed that successful conservative management of a patient with asymptomatic DIC and subsequent fever without infection is extremely rare. Conclusions Some patients with DIC and fever can continue conservative management of placenta percreta, although careful examination and monitoring are needed.

Numerous monoclonal antibodies (mAb) targeting tumor antigens have recently been developed. Antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP) via effector cells such as tumor-infiltrating natural killer (NK) cells and macrophages are often involved in mediating the antitumor activity of mAb. CpG oligodeoxynucleotides (ODN) have a potent antitumor activity and are considered to increase tumor infiltration of NK cells and macrophages. Our group previously reported significant antitumor activity of anti-bone marrow stromal antigen 2 (BST2) mAb against BST2-positive endometrial cancer cells through ADCC. In this study, we evaluated the synergistic antitumor activity of combination therapy with anti-BST-2 mAb and CpG ODN using SCID mice and elucidated the mechanisms underlying this activity. Anti-BST2 mAb and CpG ODN monotherapy had a significant dose-dependent antitumor activity (P = 0.0135 and P = 0.0196, respectively). Combination therapy with anti-BST2 mAb and CpG ODN had a significant antitumor activity in SCID mice (P

Aim Following media reports of adverse medical events surrounding human papillomavirus (HPV) vaccination and the suspension of Japanese governmental recommendation, most adolescents have refrained from receiving the vaccine. This represents a national critical event, because the incidence of cervical cancer in Japan continues to increase. Methods We conducted an Internet survey to investigate why Japanese adolescent girls decline, continue or discontinue their HPV vaccination, how their mothers influence their decision, and the mothers’ feelings about future HPV vaccination for their daughters. One thousand mothers with daughters 10–18 years of age were recruited for our questionnaire. Results Our results suggest that acceptance of the HPV vaccine was determined predominantly by the mother's perceptions of risk versus benefits, rather than the daughter's wishes. The mothers’ knowledge of the benefits of the prophylactic HPV vaccine and their attitude toward cervical cancer screening influenced their decision whether to allow their daughter to receive future vaccinations. The tenor of survey responses of those mothers who were anti-vaccine changed significantly to the positive in response to a proposed scenario where the governmental recommendation for the HPV vaccine was reinstated, whereas a hypothetical educational intervention sheet did not significantly change their attitude. Conclusions Promotion of the HPV vaccine through comprehensive education for both mothers and daughters, not only on the vaccine itself, but also about cervical cancer and screening, is required for any successful program to prevent cervical cancer.

Background: We compared survival outcomes and risk of venous thromboembolism (VTE) among patients with advanced and early-stage ovarian clear cell carcinoma (OCCC) and serous ovarian carcinoma (SOC), as well as potential links with interleukin-6 (IL-6) levels. Methods: A multicenter case-control study was conducted in 370 patients with OCCC and 938 with SOC. In a subset of 200 cases, pretreatment plasma IL-6 levels were examined. Findings: Patients with advanced OCCC had the highest 2-year cumulative VTE rates (advanced OCCC 43.1%, advanced SOC 16.2%, early-stage OCCC 11.9% and early-stage SOC 6.4%, P < 0.0001) and the highest median levels of IL-6 (advanced OCCC 17.8 pg/mL, advanced SOC 9.0 pg/mL, early-stage OCCC 4.2 pg/mL and early-stage SOC 5.0 pg/mL, P = 0.006). Advanced OCCC (hazard ratio [HR] 3.38, P < 0.0001), thrombocytosis (HR 1.42, P = 0.032) and elevated IL-6 (HR 8.90, P = 0.046) were independent predictors of VTE. In multivariate analysis, patients with advanced OCCC had significantly poorer 5-year progression-free and overall survival rates than those with advanced SOC (P < 0.01), and thrombocytosis was an independent predictor of decreased survival outcomes (P < 0.01). Elevated IL-6 levels led to poorer 2-year progression-free survival rates in patients with OCCC (50% versus 87.5%, HR 4.89, P = 0.016) than in those with SOC (24.9% versus 40.8%, HR 1.40, P = 0.07). Interpretation: Advanced OCCC is associated with an increased incidence of VTE and decreased survival outcomes, which has major implications for clinical management of OCCC.

Most adolescents in Japan have recently been refraining from receiving the human papillomavirus (HPV) vaccine, following media reports of adverse medical events surrounding the vaccination and suspension of the Japanese governmental recommendation. We have previously reported that HPV vaccination of young girls is heavily influenced by guidance from their physicians concerning the vaccine and by the knowledge and attitude of the girls’ mothers towards cervical cancer. However, it has been unclear as to how the obstetricians and gynecologists were themselves affected by the negative media reports. A questionnaire, including questions about their working status, attitudes toward HPV vaccination and about cervical cancer, and the HPV vaccination status of their daughters, was posted to obstetricians and gynecologists. None of the daughters of the responding obstetrician and gynecologists received the HPV vaccination after the announced suspension of the governmental recommendation for the vaccine. The number who received the HPV vaccine in the 6th to 9th grade in 2014 was significantly lower than those in 2012 (p = 0.012). However, 64.7 % of the responders whose daughters were eligible and in the 6th to 12th grade still intended to vaccinate their daughters in the future. Of the responders, 65 % also intended to recommend vaccination to their teenage patients. Our study revealed that obstetricians and gynecologists, like the general population, were negatively influenced by media reports of the adverse effect of the HPV vaccine and the suspension of the governmental recommendation. However, their intention to vaccinate their daughters was much higher than that of the general population. Restart of the governmental recommendation for HPV vaccines and better education about the HPV vaccine, including its adverse effects, and about cervical cancer and cervical cancer screening, are strongly recommended, for both the general public and for doctors, for improved prevention of cervical cancer.

Aim Poor visualization of the operative field due to an obscured camera lens is a problem frequently encountered while performing laparoscopic surgery. Little has been published about the prevention of lens obstruction specifically due to a contaminated camera port used for laparoscopic surgery. The aim of our study is to develop a new device, the Endowiper, for cleaning the laparoscopic port. Materials The new cleaner for the port’s valve is made from rolled gauze. To simulate a surgical environment in the laboratory, we have used pseudo-blood to smudge the port’s valve. Method In order to demonstrate the efficacy and safety of the Endowiper, we compared our method using this device with three previously reported port cleaning methods. These methods included use of gauze tightly wrapped around an endoscopic dissecting cramp, a small piece of gauze grasped by an endoscopic dissecting cramp, and a swab. We repeated the performance tests 280 times, 240 using a 12-mm trocar port and 40 with a 5-mm port. Results With the 12-mm port, the complete port clearance rate achieved was 83.3 % by Endowiper, 56.7 % by wrapped gauze, 36.7 % by small gauze, and 40.0 % by swab. Trouble rate encountered during the procedure was 0 % by Endowiper, 1.7 % by wrapped gauze, 15 % by small gauze, and 90 % by swab. For the 5-mm port, the complete port clearance rate was 85 % by Endowiper and 20 % by sterile swab. The trouble rate was 0 % by Endowiper and 30 % by swab. Endowiper had a significantly superior result related to clearance rate than the other three methods in both the 12- (p

Background The clinical impact of lympho-vascular space invasion (LVSI) in early-stage ovarian clear cell carcinoma (OCCC) is not well understood. Given the distinct tumor biology and survival patterns of OCCC, the significance of LVSI on survival outcome and treatment response was examined in OCCC. Methods A multicenter study was conducted to examine stage IA–IC3 OCCC cases that underwent primary surgical staging including lymphadenectomy. LVSI status was determined from archived histopathology slides, correlated with clinico-pathological results, chemotherapy patterns, and survival outcomes. Results LVSI was observed in 47 (20.3%) among 232 cases. In univariate analysis, LVSI was associated with older age ( p =0.042), large tumor size ( p =0.048), and stage IC ( p =0.035). In survival analysis, LVSI was associated with decreased disease-free survival (DFS, 5-year rate, 70.6% versus 92.1%, p =0.0004) and overall survival (OS, 78.8% versus 93.3%, p =0.008) on univariate analysis. After controlling for age, tumor size, stage, and chemotherapy use, LVSI remained an independent prognostic factor for decreased survival outcomes (DFS, hazard ratio [HR] 4.35, 95% confidence interval [CI] 1.73–10.9, p =0.002; and OS, HR 4.73, 95%CI 1.60–14.0, p =0.015). Among 210 cases who received postoperative chemotherapy, while regimen type did not impact survival outcome regardless of LVSI status (DFS, p =0.63), the number of administered cycles showed a survival benefit towards ≥6cycles for patients with LVSI-positive tumors (DFS, p =0.009; and OS, p =0.016). Conclusion LVSI is an important marker to predict survival outcome of stage I OCCC. Regardless of chemotherapy type, patients with stage I OCCC showing LVSI may benefit from receiving postoperative chemotherapy.

Background Finding ways to improve the cervical cancer screening rates among young women has been seen as a critical national health problem in many countries, including Japan. The aim of the present study was to evaluate the effects of a free-coupon program for cervical cancer screening conducted by a local government under financial support from the Japanese national government. Methods The personal cervical cancer screening information was analyzed for all female residents of Toyonaka City, including any past screening history and clinical results since the year 2009, when a free-coupon program for screening was started. These results were compared to results from 2008, prior to implementation of the free-coupon screening program. Results The screening rates of women eligible for the free-coupon peaked dramatically compared to women of similar age who paid for their screening; however, the rates for the ineligible-age population also increased significantly in parallel to those in the free-coupon program, possibly by indirect peer and publicity effects. In women aged 20 to 25 years, the consecutive screening rate after a free-coupon screening was significantly lower than for those women who received a regular residential screening. After a free-coupon screening, the rate for participating in consecutive screenings depended significantly on the institution where the participant received her first screening test. Conclusions These results suggest that, for a generation of young women 20–25 years of age, a free-coupon program for cervical cancer screening was effective in increasing the first-time participation rate for screening; however, the increase in first-time participation did not lead to the expected increase in consecutive screenings.

Ovarian cancer is the leading cause of gynecologic cancer-related deaths and novel therapeutic strategies are required. Programmed cell death 1 and programmed cell death ligand 1 (PD-L1), which are key mediators of host immune tolerance, are associated with ovarian cancer progression. Recent evidence indicates the importance of IFNγ-induced PD-L1 for immune tolerance in ovarian cancer. This study aimed to reveal the therapeutic potential of suppressor of cytokine signaling 1 (SOCS-1), an endogenous inhibitor of the Janus kinase (JAK)-STAT signaling pathway, for the treatment of ovarian cancer. IHC assessment revealed that patients with ovarian cancer with high intratumoral STAT1 activation exhibited poor prognosis compared with patients with low STAT1 activation (

Background Maternal outcomes after conservative management of placenta percreta are poorly understood. Objective To assess the success and complication rates of conservative management of placenta percreta. Search strategy The PubMed, MEDLINE, and Scopus databases were searched for English-language articles published between January 1990 and December 2016, using combinations of search terms related to conservative management of placenta percreta. Selection criteria Only studies describing conservative treatment for placenta percreta (without placental removal) were included in the systematic review. Data collection and analysis There were 44 studies included and maternal outcomes were reviewed and categorized among 72 patients. Main results The uterus was preserved among 42 (58%) patients and severe complications developed among 40 (56%). Prophylactic uterine artery embolization (UAE) did not improve success rates (P=0.807); however, the mean time for complete placental resorption was lower in the UAE group than in the non-UAE group (22.4 weeks vs 35.3 weeks; P=0.014). Hysterectomy was performed at a mean of 44.6 days after cesarean delivery. Among the 23 patients with hysterectomy-related complications, 18 (78%) experienced bladder injury, intraoperative bleeding (>2000 mL), or both. The use of chemotherapy did not improve success rates (P=0.064). Conclusions The present systematic review revealed high maternal morbidity during conservative management of placenta percreta.

Key Clinical Message Placenta percreta (with bladder invasion) is a rare obstetric condition with the risk of massive intraoperative hemorrhage. In these cases, the combination of a transverse uterine fundal incision and retrograde cesarean hysterectomy could be useful to minimize maternal hemorrhage and avoid severe bladder injury.

// Akiko Morimoto 1,2 , Satoshi Serada 2 , Takayuki Enomoto 3 , Ayako Kim 2 , Shinya Matsuzaki 1 ,Tsuyoshi Takahashi 2,4 ,Yutaka Ueda 1 , Kiyoshi Yoshino 1 , Masami Fujita 1 , Minoru Fujimoto 2 , Tadashi Kimura 1 and Tetsuji Naka 2 1 Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Japan 2 Laboratory for Immune Signals, National Institute of Biomedical Innovation, Japan 3 Department of Obstetrics and Gynecology, Niigata University Medical School, Japan 4 Department of Surgery, Osaka University Graduate School of Medicine, Japan Correspondence: Tetsuji Naka , email: // Keywords : Annexin A4; platinum resistance; annexin repeat; chloride ion Received : April 04, 2014 Accepted : August 03, 2014 Published : August 04, 2014 Abstract Platinum resistance has long been a major issue in the treatment of various cancers. We previously reported that enhanced annexin A4 (ANXA4) expression, a Ca 2+ -regulated phospholipid-binding protein, induces chemoresistance to platinum-based drugs. In this study, we investigated the role of annexin repeats, a conserved structure of all the annexin family, responsible for platinum-resistance as well as the effect of knockdown of ANXA4. ANXA4 knockdown increased sensitivity to platinum-based drugs both in vitro and in vivo . To identify the domain responsible for chemoresistance, ANXA4 deletion mutants were constructed by deleting annexin repeats one by one from the C terminus. Platinum resistance was induced both in vitro and in vivo in cells expressing either full-length ANXA4 or the deletion mutants, containing at least one intact annexin repeat. However, cells expressing the mutant without any calcium-binding sites in the annexin repeated sequence, which is essential for ANXA4 translocation from the cytosol to plasma membrane, failed to acquire platinum resistance. After cisplatin treatment, the intracellular chloride ion concentration, whose channel is partly regulated by ANXA4, significantly increased in the platinum-resistant cells. These findings indicate that the calcium-binding site in the annexin repeat induces chemoresistance to the platinum-based drug by elevating the intracellular chloride concentration.

Administration of the human papillomavirus (HPV) vaccine decreased dramatically in Japan after extensive news of adverse vaccine events and suspension of the governmental recommendation for the vaccine. In this study, we investigated the knowledge and acceptance of vaccinated adolescents concerning cervical cancer, cancer screening and the HPV vaccine. Furthermore, we analyzed whether and by how much the news affected acceptance of the vaccination. This study was conducted as a part of Osaka Clinical resEArch of HPV vacciNe (OCEAN) study. A questionnaire was distributed to 2,777 study registrants. The response rate was 38 %. The recognition rate of the news of the vaccine’s adverse events was 80 %; it was 68 % for awareness of the government’s announcement of the suspension of its recommendation for the vaccine. Among those who had a chance to hear or see the negative news during their vaccination period, 46 (60 %) continued vaccination while knowing of the news, 22 (29 %) discontinued vaccination, and 9 (11 %) continued vaccination without an awareness of the news. Reports of the vaccine’s adverse events were the main reason for not continuing the vaccination series. Those who consulted doctors after hearing the adverse news were significantly more likely to continue their vaccinations than those who did not. Our results should help in understanding the need for a strong promotion of vaccine usage and cancer screening after future retraction of the recommendation suspension. This may apply to other countries with an unsatisfactory rate of HPV vaccination due to fears of adverse vaccine events.

To evaluate the effect of lymphovascular space invasion on survival of patients with early-stage epithelial ovarian cancer.A multicenter retrospective study was conducted for patients with stage IA-C epithelial ovarian cancer who underwent primary comprehensive surgery including lymphadenectomy. Histopathology slides for ovarian tumors were examined by gynecologic pathologists for the presence or absence of lymphovascular space invasion. Survival analysis was performed examining tumoral factors.A total of 434 patients were included in the analysis. Lymphovascular space invasion was detected in 76 (17.5%) patients associated with histology (P=.042) and stage (P=.044). Lymphovascular space invasion was significantly associated with decreased survival outcomes (disease-free survival, 5-year rate 78.4% compared with 90.7%, P=.024 and overall survival, 84.9% compared with 93.2%, P=.031) in univariate analysis. In multivariate analysis, lymphovascular space invasion did not remain a significant variable for disease-free survival (hazard ratio [HR] 1.98, 95% confidence interval [CI] 0.97-3.97, P=.059) or overall survival (HR 2.41, 95% CI 0.99-5.85, P=.052). Lymphovascular space invasion was associated with increased risk of hematogenous and lymphatic metastasis (HR 4.79, 95% CI 1.75-13.2, P=.002) but not peritoneal metastasis (P=.33) in multivariate analysis. Among lymphovascular space invasion-expressing tumors, patients who received fewer than six cycles of postoperative chemotherapy had significantly poorer disease-free survival than those who received six or more cycles (HR 4.59, 95% CI 1.20-17.5, P=.015).Lymphovascular space invasion is an important histologic feature to identify a subgroup of patients with increased risk of recurrence in stage I epithelial ovarian cancer.III.

The objective of the study is to identify the risk factors associated with recurrent/persistent disease and cervical stenosis after conization. Five hundred twenty-two (522) cases of high-grade intraepithelial lesions treated by conization were retrospectively reviewed. Risk factors associated with recurrent/persistent disease were analyzed by univariate and multivariate analysis using a Cox hazard regression model. Factors that could potentially affect the risk of cervical stenosis were examined by univariate and by multivariate analysis using the χ 2 test and logistic regression, respectively. Recurrent/persistent diseases and cervical stenosis occurred in 4.8% and 5.4% of the patients, respectively. Age ≥46 years [hazard ratio (HR) 3.6, 95% CI 1.36–10.3, p = 0.0092] and surgical margin involvement (HR 13.44, 95% CI 5.07–46.37, p

Small cell neuroendocrine carcinoma (SCNEC) of uterine cervix is a rare tumor accounting for approximately 1-2% of uterine cervical tumors. SCNEC of uterine cervix is highly invasive and has an extremely poorer prognosis than other histologic types for which no standard treatment is established. To establish a new management strategy against SCNEC of uterine cervix, we developed a drug sensitivity assay based on a 3D primary culture system. We previously developed the cancer tissue-originated spheroid (CTOS) method, a primary culture method from patients’ tumors. To date, we established a panel of 12 SCNEC CTOS lines with the success rate of 100%. For each line, multiple CTOSs were placed in one well of a 96 well plate and dose response analysis was performed for seven anticancer drugs; paclitaxel, carboplatin, irinotecan, SN-38, cisplatin, etoposide and gemcitabine. After 7 days of culture, the CTOSs viability was evaluated by measuring intracellular ATP levels, corrected by the size of CTOS at day0. All drugs had substantial variations in sensitivity among the lines. Cerv54 was far more sensitive to irinotecan than other lines while was similarly sensitive to SN-38. We revealed that cancer cells of cerv54 had high levels of carboxylesterase(CES)1 expression, which converts irinotecan to SN38. Since cerv54 with CES1 knockdown by pGFP-C-shCES1 lentivirus had lower sensitivity than sh-scramble, CES1 expression is related to the irinotecan sensitivity in cerv54. CES1 expression in cancer cells may be useful for predicting the effect of irinotecan based chemotherapy. In addition, this study indicates that sensitivity test using CTOS might be applicable to precision medicine by selecting sensitive drugs for each patient. Citation Format: Mie Tanaka, Satoshi Kubota, Yu Ito, Yumiko Kiyohara, Hiroko Endo, Jumpei Kondo, Satoshi Nakagawa, Akiko Okazawa, Shinya Matsuzaki, Toshihiro Kimura, Eiji Kobayashi, Yutaka Ueda, Kiyoshi Yoshino, Shoji Kamiura, Tadashi Kimura, Masahiro Inoue. Ex vivo drug sensitivity assay with a panel of cancer patient-derived spheroids of small cell neuroendocrine carcinoma of uterine cervix [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 33.

Objective To analyze the efficacy and safety of combination chemotherapy of docetaxel and irinotecan for paclitaxel and carboplatin (TC) -refractory or -resistant ovarian carcinomas and for first treatment of primary clear cell and mucinous ovarian carcinomas. Study design Between 2002 and 2009, we conducted a prospective Phase II study of the efficacy and safety of combination chemotherapy using docetaxel and irinotecan in 62 patients with TC-refractory or -resistant ovarian carcinoma cases (GOGO-OV2) and 15 patients with primary clear cell and mucinous ovarian carcinoma cases (GOGO-OV3). The dose of docetaxel and irinotecan was determined during our previous Phase I study. Results A docetaxel plus irinotecan regimen provided a 53% response rate, 6 months progression-free survival (PFS), and 12 months overall survival (OS) for primary clear cell and mucinous ovarian carcinomas (similar to TC therapy). The differences of anti-tumor and survival effects between refractory and resistant cases were not statistically significant. The regimen also provided a 15% response rate, 5 months PFS, and 15 months OS for TC-refractory or TC-resistant cases, when used as a second-line chemotherapy. These data are similar to previous reports, however, our study provides the first data exclusively for the cases refractory or resistant to a gold standard TC therapy as a second-line chemotherapy. The regimen was demonstrated to be well tolerable. Conclusion Combination chemotherapy of docetaxel and irinotecan may be a useful option to treat TC-refractory/resistant cases and primary clear cell and mucinous adenocarcinoma cases of ovarian carcinoma.

With the aim of constructing a system for monitoring sterilization under atomic oxygen, we investigated the applicability of the quartz crystal microbalance (QCM) system, to atomic oxygen generated in a cold oxygen plasma apparatus. We have exposed microorganisms, such as Bacillus subtilis and Aspergillus niger , examined the effects of such exposure, and observed the inactivation properties of these microorganisms. We have confirmed that there is a positive correlation between atomic oxygen exposure and inactivation of microorganisms, quantified by the QCM method using fluorocarbon thin films, and have investigated the relevant inactivation mechanism through scanning electron microscope (SEM) observation and spectrum analysis.

Objective The Shimodaira-Taniguchi conization procedure addresses the disadvantages of the loop electrosurgical excision procedure (LEEP) by using a high frequency current and a triangular probe with a linear excision electrode to extract the tissue as a single informative specimen, without incurring accompanying thermal trauma. The aim of the present study was to analyze the surgical efficacy of the Shimodaira-Taniguchi conization procedure for adenocarcinoma in situ (AIS) of the uterine cervix. Study design At the Osaka University Hospital, conization using the Shimodaira-Taniguchi procedure has long been routinely performed for AIS. Medical records of patients during the period from 2005 to 2011, whose post-conization diagnosis was AIS, were retrospectively analyzed. A literature review was conducted of the PubMed database to clarify the surgical outcome efficacy of the Shimodaira-Taniguchi procedure compared to other procedures. Results During the study period, a post-conization diagnosis of AIS was made in 10 patients. A positive resection margin was detected in 4 of the 10 cases (40%), and residual disease was observed in 3 cases (30%). A review of the relevant literature indicates that the rate of positive margin and residual disease by the Shimodaira-Taniguchi procedure, including our cases, was not significantly different from the cold knife, LEEP or laser procedures ( p =0.32, 0.99, and 0.40, respectively, for positive margin, and p =0.76, 0.94, and 0.063, respectively, for residual disease). Conclusion AIS was demonstrated to be efficaciously treated, with a low risk of residual disease, by the Shimodaira-Taniguchi conization procedure. Further study is still needed to establish a standard of conservative treatment for AIS.