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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 serous ovarian carcinomas (SOCs). The medical records and slides of 84 SOCs, including 13 with neoadjuvant chemotherapy (NAC), were retrospectively reviewed. The following clinicopathological parameters were noted: age at the diagnosis, CA125 level, 2014 FIGO stage, architectural grade, nuclear grade, presence of ITB, lymphovascular space invasion (LVSI), mitotic index and lymph node metastasis. ITB was found in 65 (77.4%) of the 84 SOCs. The presence of ITB was significantly correlated with a higher level of CA125, an advanced 2014 FIGO stage, a worse architectural grade, and the presence of LVSI. The median progression-free survival (PFS) was 20 months in women with SOC with ITB and 38 months in women with SOC without ITB (P

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.

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.

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.

Oxytocin (OXT) is produced in the hypothalamic nuclei and is secreted into systemic circulation from the posterior pituitary gland (PP). In the central nervous system, OXT regulates behaviours including maternal and feeding behaviours. Our aim was 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 in the hypothalamic nuclei and PP was most strongly expressed during the oestrus stage in female rats and decreased significantly in ovariectomised rats. Oestrogen replacement caused significant increases in the fluorescent intensities in the hypothalamic nuclei and PP in a dose-dependent manner. This was also demonstrated in feeding behaviour and hypothalamic Fos neurons using immunohistochemistry. Hypothalamic OXT expression was oestrogen dependent and could be enhanced centrally by the administration of oestrogen.

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.

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 β-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/β-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 β-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/β-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.

Neonatal sepsis continues to be a global problem with significant morbidity and mortality, because of the difficulty in predicting its onset with clinical symptoms alone. Thus, the presence of biomarkers is useful for the diagnosis of neonatal sepsis. Presepsin is a 13-kDa truncated form of soluble CD14 that is produced through proteolytic cleavage on activated monocytes. Presepsin, consisting of 64 amino acid residues, has been proposed as a reliable biomarker for the early diagnosis of sepsis in neonates. However, some biomarkers for the diagnosis of sepsis are elevated during the early neonatal period due to physiological variation, whereas such variation in presepsin levels is uncertain. The objective of this study is to investigate the physiological variation in plasma presepsin levels during the early neonatal period. This prospective study included 30 full-term healthy neonates, including 15 neonates delivered by cesarean section. Plasma presepsin levels were examined at birth and on the first day and the fifth day of life in neonates, and the levels on the 5th day of life were lower than those at any other points (P < 0.001). Moreover, there was no significant difference of plasma presepsin levels between neonates delivered vaginally and by cesarean section. The physiological variation in plasma presepsin levels was observed during the early neonatal period. Attention needs to be paid when measuring plasma presespsin levels for the screening of sepsis during the early neonatal period.

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.

The aim of this report was to evaluate the impact of hormone replacement therapy (HRT) on lymphocytic infiltration of the endometrium in postmenopausal women.This study included 58 Japanese patients who had undergone hysterectomy at the University Hospital of Occupational and Environmental Health, Japan. Before surgery, nine patients had received 17β-estradiol (E2), 0.72 mg transdermally for 2-8 weeks (E2 group); 16 patients had received an Estra-1,3,5(10)-triene-3,16α, 17β-triol (E3) vaginal tablet 0.5 mg per month five times (E3 group); and 19 patients had received 17β-estradiol, 0.62 mg, and norethindrone acetate (P), 2.70 mg for 3-16 weeks (E2 + P group). Fourteen patients received no HRT (control group). We examined uterine tissue specimens immunohistochemically for CD45+, CD3+, CD4+, CD8+, CD20+, CD56+, and Ki67 antigen-positive cells.The numbers of CD56 + cells were significantly increased in the E2 group compared with all other groups (E2 vs. E3: 7.0 vs. 0.75, p = 0.017; E2 vs. E2 + P: 7.0 vs. 0.58, p = 0.009; E2 vs.7.0 vs. 0.43, p = 0.010). The numbers of CD3+ cells were significantly increased in the E2 group compared with the control group (149.3 vs. 42.6, p = 0.008).17β-Estradiol induced the proliferation of endometrial uterine natural killer cells (CD56+) in postmenopausal women.

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.

A 75-year-old woman complained of anuria and a sense of discomfort with severe pelvic organ prolapse (POP). We planned tension-free vaginal mesh (TVM) surgery after curing mucosal defects and completing treatment for diabetes mellitus. Anuria and pyelonephritis relapsed repeatedly due to the failure of ring pessary therapy. Surgical treatment was required emergently. We performed a total laparoscopic hysterectomy and uterosacral ligament colpo-suspension (Shull’s method). Although the vaginal apex was supported to a good position, cystocele occurred six months after the initial surgery. A TVM procedure for recurrent cystocele was performed after curing the mucosal defects, and after the improvement of glycemic control. Transvaginal native tissue repair has the advantages of low risk of ureter injury, firm colpo-suspension, and no need for mesh usage. On the other hand, it is not good at treating cystocele. Transvaginal native tissue repair should prove to be a useful surgical option for apical support without mesh.

Aim The purpose of this study is to present alternative diagnostic criteria of colposcopy using new parameters. Methods Colposcopic photographs were reviewed in 1649 patients from the past 23 years, including 283 benign lesions, 327 low-grade squamous intraepithelial lesions (LSIL; cervical intraepithelial neoplasia 1), 549 high-grade squamous intraepithelial lesions (HSIL; cervical intraepithelial neoplasia 2/3), 78 microinvasive cancers, and 412 invasive cancers. Abnormal colposcopic findings were divided into: minor or major; single, or a combination of two or three findings; and under half or over half circumferential size. Histopathological backgrounds were investigated according to these new parameters of colposcopic findings. Results Minor abnormal colposcopic findings were observed in 21% of LSIL, and major abnormal findings were seen in 52% of LSIL, 86% of HSIL, and 86% of microinvasions. A single major abnormal finding was observed in 64% of the cases with LSIL, while two abnormal findings were observed in 43% of HSIL, and three abnormal findings were observed in 44% of microinvasions. In qualifying major abnormal colposcopic findings, under half size was detected in 91% of LSIL and 74% of HSIL, and over half size was observed in 58% of microinvasions. From these results, the following diagnostic criteria were instituted: (i) LSIL – single, minor or major findings and under half size; (ii) HSIL – two or three major findings and under half size; (iii) microinvasion – three major findings and over half size; and (iv) invasive cancer – irregular surface with atypical vessels. Conclusion Our new diagnostic criteria of colposcopy are fully acceptable, based on their similar level of accuracy to cytology.

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.

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

Background Several biomarkers for the diagnosis of sepsis are elevated during the early neonatal period due to physiological variations. The aim of this study was to investigate the physiological variation in neutrophil CD64 (nCD64) expression during the early neonatal period and the change in nCD64 expression in neonates with noninfectious diseases. Methods Of 71 neonates enrolled in this prospective study, 5 and 51 were diagnosed as having bacteremia and noninfectious diseases, respectively. Fifteen healthy neonates were enrolled as normal controls. Peripheral white blood cell counts, serum C-reactive protein and procalcitonin levels, and nCD64 expression were examined at birth and on the first and fifth day of life in neonates with noninfectious diseases and healthy neonates. In neonates with bacteremia, these markers were measured at onset. Results nCD64 expression was significantly higher in neonates with bacteremia (median, 1,992) than in those with noninfectious diseases (1,823, p

Aim Recent developments in transperineal ultrasound imaging of the pelvis have prompted trials to objectively evaluate labor progression for labor management. We evaluated the accuracy of transperineal ultrasound in diagnosing arrest of labor. Methods Transperineal ultrasound and digital pelvic examinations were performed simultaneously in 63 term laboring patients (singleton fetuses in cephalic presentation). We analyzed a total of 216 ultrasound images (Sonography Volume Computer Aided Display Labor [Sono VCAD Labor®] installed in Voluson E8 ultrasound). We examined the correlation between the three ultrasound parameters head direction (HD), progression distance (PD), and progression angle (PA), and digital pelvic examination findings during labor in a transvaginal delivery group and an arrested labor group. Results The coefficient of correlations between HD/PD/PA and cervical dilation/fetal station were 0.667/0.657/0.706 and 0.667/0.751/0.803, respectively. The three parameters had strong correlations with digital pelvic examination (P < 0.05). In the 11 cases (17%) of cesarean section due to arrested labor, the position of the fetal head was visually unchanged on sequential ultrasound images. According to receiver operating characteristic curves, the significant cut-offs for HD, PD, and PA for arrested labor were 105° (P = 0.048), 35 mm (P = 0.048), and 120° (P = 0.001), respectively. Conclusions Transperineal ultrasound imaging is helpful for objective evaluation of labor progression and the diagnosis of arrested labor.

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.

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

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-naive 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).

The p53 signature (p53S) has been proposed to be a marker of the earliest phase of development of endometrial serous carcinoma. We examined the presence of p53S in the background endometrium in cases of endometrial carcinoma. From a series of 351 endometrial carcinomas, 225 (64.1 %) lesions, for which slides of the adjacent noncancerous endometrium were available for review, were included. Expression of estrogen receptor (ER)-alpha, Ki-67, and p53 in the adjacent endometrium was studied by immunohistochemistry. The p53S was defined as the presence of morphologically benign endometrial epithelial cells with moderate to strong intensity of p53 immunostaining. Of the 225 noncancerous endometrium samples, 34 consisted of hyperplastic and 191 of non-hyperplastic endometrium. A p53S was found in 22 cases (mean age 64.2 years), 2 in hyperplastic, and 20 in non-hyperplastic background endometrium. All p53S-positive cases also expressed ER-alpha; their median Ki-67 labeling index (LI) was 4.0 % (range 0.0 to 21.0 %). The two cases with hyperplastic p53S-positive background endometrium were in association with a grade 1 endometrioid tumor in a premenopausal woman with Lynch syndrome. Of the 152 cases of endometrioid adenocarcinomas with non-hyperplastic endometrium, 12 (8 %) were p53S positive, none of which associated with EIC. Of the 21 cases of serous carcinoma, five (24 %) were p53S positive, 4 of which (19 %) associated with EIC while in 5 others (24 %) EIC was found without p53S. Of three clear cell adenocarcinomas, none were p53S positive while two contained EIC without p53S. Of 15 carcinosarcomas, 3 (20 %) were p53S positive, all of which with EIC while 6 others (40 %) were associated with EIC but without p53S. Of the 8 non-endometrioid tumors with p53S, 7 (88 %) were associated with EIC. p53S is thought to be associated with precancerous lesions of non-endometrioid tumors, including carcinosarcomas.

The SMARCE1 (SWI / SNF-related, matrix-associated, and actin-dependent regulator of chromatin, subfamily e, member 1) encodes BAF57 protein. Previously, we reported that BAF57 is a predictive marker of endometrial carcinoma. In this study, we investigated BAF57 expression in ovarian cancer cell lines and their sensitivities to cisplatin, doxorubicin, paclitaxel, and 5-fluorouracil. BAF57 expression was strongly correlated with sensitivities to cisplatin, doxorubicin, and 5-fluorouracil in 10 ovarian cancer cell lines. Paclitaxel sensitivity was also correlated with BAF57 expression, but without significance. In A2780 ovarian cancer cells, knockdown of BAF57 using specific siRNA increased cell cycle arrest at G1 phase and the sensitivities to these anticancer agents. cDNA microarray analysis of A2780 cells transfected with BAF57 siRNA showed that 134 genes were positively regulated by BAF57, including ATP-binding cassette, sub-family G (WHITE), member 2 (ABCG2) encoding breast cancer resistance protein (BCRP). We confirmed that knockdown of BAF57 decreased BCRP expression in ovarian cancer cells by Western blot analysis, and that ABCG2 gene expression might be regulated transcriptionally. These results suggested that BAF57 is involved in ovarian cancer cell growth and sensitivity to anticancer agents, and that BAF57 may be a target for ovarian cancer therapy.

Objective: We investigated the association of positive peritoneal cytology with prognosis in uterine cervical cancer. Study Design: We reviewed the medical records and cytologic materials of 225 Japanese patients with FIGO IB1-IVB uterine cervical cancer who had undergone surgery at our University Hospital between 1993 and 2012. Univariate and multivariate regression analyses were performed for statistical analysis. Results: Positive peritoneal cytology was noted in 6 of 225 patients (2.7%). Positive peritoneal cytology was found in 4 of 149 patients (2.6%) with squamous cell carcinoma (SCC) and in 2 of 70 patients (2.8%) with non-SCC (p = 0.9434). The 5-year survival rate of patients with positive peritoneal cytology was significantly lower than that of patients with negative cytology (50 vs. 84.6%, p = 0.001) in univariate survival analysis. However, peritoneal cytology no longer remained significant in multivariate analysis. Conclusion: Although we conclude that positive peritoneal cytology in uterine cervical cancer is a poor prognostic factor, further investigation and multi-institutional studies are necessary.

Objectives: The aim of this study is to introduce protocols for choosing trans-arterial embolization (TAE) or surgical hemostasis as an initial therapy for obstetric hemorrhage. Materials and Methods: From 2002 to 2011 at our hospital, the medical records of the patients who underwent TAE or surgical hemostasis for obstetric hemorrhage were reviewed to assess the following data: The causes of obstetric hemorrhage, Shock Index (SI) and obstetrical disseminated intra-vascular coagulation (DIC) score, amount of bleeding, transfusion, and operation time. Results: Twenty-five patients underwent TAE and six underwent surgical hemostasis. SI and obstetrical DIC score of the TAE group were 1.0 (0.4 - 2.2) and 6.0 (1 - 32), respectively. They were significantly lower than those of the surgical hemostasis group (SI: 1.6, obstetrical DIC score: 12.5, p < 0.05). Though the hemorrhage could be controlled sufficiently in 23 cases of the TAE group, 5 cases went into shock during TAE. The SI and obstetrical DIC score of shock group were 1.2 (1 - 2) and 10 (2 - 32), respectively. Conclusion: Though TAE is a useful therapy to control obstetric inevitable hemorrhage, special attention should be paid to the vital signs during TAE, especially in cases where SI and/or obstetrical DIC score are higher than 1.2 and 10, respectively.

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.

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 β-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.

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.

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.This study investigated the relationship between GalNAc-T6 expression and cell adhesion molecules in 218 endometrial carcinomas by immunohistochemistry.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 β-catenin expression were not significantly associated with improved overall survival.GalNAc-T6 might be related to cell-cell adhesion in the early phase of cancer invasion in endometrial carcinoma.

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.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.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).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.

Rie Urabe,1 Toru Hachisuga,1 Taeko Ueda,1 Toshinori Kawagoe,1 Tomoko Kurita,1 Seiji Kagami,1 Masanori Hisaoka,2 Yoshihisa Fujino3 1Department of Obstetrics and Gynecology, 2Department of Pathology and Oncology, 3Department of Preventive Medicine and Community Health, School of Medicine, University of Occupational and Environmental Health, Iseigaoka, Yahatanishi-ku, Kitakyushu, Japan 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

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.

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.

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. Electronic supplementary material The online version of this article (doi:10.1186/s12885-017-3071-5) contains supplementary material, which is available to authorized users.

Uterine cervical cancer is the most common primary gynecologic malignant tumor in Japan. Conventional cervical screening Papanicolaou (Pap) test has been shown to be extremely effective in reducing cervical cancer incidence and mortality, but the consultation rate for cancer screening in Japan is markedly low, at 20% of prescribed subjects, in comparison with other developed countries. In 2001, 15,501 women (6.8%) received a Pap test in Kitakyushu City, and that was less than half of national average. From 2009, free coupons for uterine cervical cancer screening were distributed to Japanese woman who were 20, 25, 30, 35 or 40 years of age as part of the project for women-specific cancer screening. The rate of participation in Pap testing was 22.3% in 2012, with 31,970 women receiving cervical tests. It was almost as high as the national level. It's obvious that high risk human papillomavirus (HPV) is responsible for cervical cancer incidence and HPV mainly infects through sexual practice. The rate of early cervical neoplasms and invasive cancers is currently increasing in young women. Abnormal Pap tests were detected in 2.3% of the women in 2008. To increase the population's participation in this screening process, a cost-effective and efficient system should be established. National and local governments, medical institutions, companies, and educational institutions must have an accurate understanding of the current situation, and take an assertive approach in order to decrease the mortality rate of uterine cervical cancer.

Ovarian yolk sac tumor (YST) is characterized by endodermal differentiation, and represents approximately 20% of malignant germ cell neoplasms. The age distribution of patients reported with YST ranges from 16 months to 46 years, but most patients are under 30 years of age (Talerman and Vang, 2011). YST is often found admixed with other types of germ cell neoplasm, but YST associated with epithelial ovarian carcinoma is extremely rare (Talerman and Vang, 2011). Unlike pure YST, YST associated with epithelial ovarian carcinoma is reported in elderly patients, and has a poor response to chemotherapy. Here we describe a case of YST associated with endometrioid adenocarcinoma in a postmenopausal woman. Our patient responded favorably to treatment with Docetaxel and Carboplatin combination chemotherapy, and has survived without evidence of relapse for 48 months postoperatively including a long term follow-up program. To the best of our knowledge, this is the first report of YST associated with endometrioid adenocarcinoma with longterm (> 48 months) successful therapy treatment, according to a Medline search of English publications.

Aim The aim of this study is to look at the weak points of tension-free vaginal mesh (TVM) operation for pelvic organ prolapse by reviewing recurrent cases. Methods Five hundred and twenty-six transobturator TVM operations were performed at the University of Occupational and Environmental Health hospital from August 2006 to December 2011. Thirty-seven patients with pelvic organ prolapse quantification (POP-Q) stage II or higher after their initial operations were diagnosed as recurrent and were enrolled in the present study. The patients' characteristics, procedures of the initial and second operations, and the recurrence rates in the pelvic organs were retrospectively reviewed. Results The median age, parity and body mass index of the patients were 66.5 years (range, 48–80), 2.2-times (range, 1–5) and 24.1 kg/m2 (range, 17.6–32.1), respectively. The mean/median follow-up periods of the whole group were 29.7/35.9 months and the recurrent prolapse rate was 7.0% (37/526 cases). We performed reoperations in eight cases (8/526 cases; 1.5%). The median recurrent period after the initial operations was 6.9 months (range, 1–24). All recurrent cases showed severe prolapse with POP-Q stage III to IV before the initial operations. The uterus showed the most frequent recurrent prolapse after anterior posterior TVM or anterior TVM. Conclusion Because the uterus is the most recurrent organ after TVM operations, TVM operations may not be sufficient for apical suspension.