Consistency between Primary Uterine Corpus Malignancies and Their Corresponding Patient-Derived Xenograft Models.

Patient-derived xenograft (PDX) models retain the characteristics of tumors and are useful tools for personalized therapy and translational research. In this study, we aimed to establish PDX models for uterine corpus malignancies (UC-PDX) and analyze their similarities. Tissue fragments obtained from 92 patients with uterine corpus malignancies were transplanted subcutaneously into immunodeficient mice. Histological and immunohistochemical analyses were performed to compare tumors of patients with PDX tumors. DNA and RNA sequencing were performed to validate the genetic profile. Furthermore, the RNA in extracellular vesicles (EVs) extracted from primary and PDX tumors was analyzed. Among the 92 cases, 52 UC-PDX models were established, with a success rate of 56.5%. The success rate depended on tumor histology and staging. The pathological and immunohistochemical features of primary and PDX tumors were similar. DNA sequencing revealed similarities in gene mutations between the primary and PDX tumors. RNA sequencing showed similarities in gene expressions between primary and PDX tumors. Furthermore, the RNA profiles of the EVs obtained from primary and PDX tumors were similar. As UC-PDX retained the pathological and immunohistochemical features and gene profiles of primary tumors, they may provide a platform for developing personalized medicine and translational research.

Evaluation of the one-step nucleic acid amplification assay for detecting lymph node metastasis in patients with cervical and endometrial cancer: A multicenter prospective study.

OBJECTIVE: This multicenter study aimed to evaluate the accuracy of the one-step nucleic acid amplification (OSNA) assay in diagnosing lymph node metastasis (LNM) in patients with cervical and endometrial cancers. METHODS: Surgically removed LNs from patients with cervical and endometrial cancer were sectioned at 2-mm intervals along the short axis direction and alternately examined using the OSNA assay and conventional histopathological examination. Ultrastaging (200-µm LN sections) was performed for metastatic LNs using hematoxylin and eosin staining and immunostaining with an anti-CK19 antibody in cases where the OSNA assay and histopathological examination (performed using 2-mm LN sections) results showed discordance. RESULTS: A total of 437 LNs from 133 patients were included; 61 patients (14%) showed metastasis by histopathological examination, with a concordance rate of 0.979 (95% confidence interval [CI]: 0.961-0.991) with the OSNA assay. The sensitivity and specificity of the OSNA assay were 0.918 (95% CI: 0.819-0.973) and 0.989 (95% CI: 0.973-0.997), respectively. Discordance between the two methods was observed in nine LNs (2.1%), and allocation bias of metastatic foci was identified as the major cause of discordance. CONCLUSIONS: The OSNA assay showed equally accurate detection of LN metastasis as the histopathological examination. We suggest that the OSNA assay may be a useful tool for the rapid intraoperative diagnosis of LN metastasis in patients with cervical and endometrial cancers.

Oncologic outcomes in elderly patients who underwent hysterectomy for endometrial cancer: a multi-institutional survey in Kinki District, Japan.

BACKGROUND: The goal of this study is to assess the oncologic outcomes of elderly patients who underwent hysterectomy for endometrial cancer across three variables: hysterectomy approach, lymph node resection, and adjuvant therapy. METHODS: Hospital records of patients aged ≥ 70 years who underwent hysterectomy for endometrial cancer were obtained from 19 institutions. Patients were categorized into three risk groups: low, intermediate, and high. In each group, disease-free survival and overall survival were compared according to hysterectomy approach, lymph node resection, and adjuvant therapy using Kaplan-Meier method. Cox regression analysis with a 95% confidence interval was performed to estimate relative risk (RR) of death. RESULTS: A total of 1246 patients were included. In the low-risk group, the adjusted RR for death for minimally invasive surgery (MIS) versus laparotomy and lymph node resection versus no lymph node resection were 0.64 (0.24-1.72) and 0.52 (0.24-1.12), respectively. In the intermediate-risk group, the adjusted RR for death for MIS versus laparotomy, lymph node resection versus no lymph node resection, and adjuvant therapy versus no adjuvant therapy were 0.80 (0.36-1.77), 0.60 (0.37-0.98), and 0.89 (0.55-1.46), respectively. In the high-risk group, the adjusted RRs for death for lymph node resection versus no lymph node resection and adjuvant therapy versus no adjuvant therapy were 0.56 (0.37-0.86) and 0.60 (0.38-0.96), respectively. CONCLUSIONS: MIS is not inferior to laparotomy in uterine-confined diseases. Lymph node resection improved the outcome for all disease stages and histological types. In contrast, adjuvant therapy improved the outcomes only in high-risk patients.

Postsurgical urodynamic study of total laparoscopic nerve-sparing radical hysterectomy for uterine cervical cancer.

AIM: To evaluate the impact on urodynamic results between the laparoscopic nerve-sparing radical hysterectomy (LRH) following a step-by-step procedure and abdominal nerve-sparing radical hysterectomy (ARH) for patients with uterine cervical cancer. METHODS: This retrospective study enrolled 76 patients with cervical cancer: 35 in the LRH group and 41 in the ARH group. We analyzed their postoperative bladder function in a urodynamics study and examined the volume of resected pelvic nerves contained in parametrial sections using S-100 antibody staining. RESULTS: Estimated blood loss and hospital stay after operation for the LRH group were significantly better than those in the ARH group (p < 0.0001). As well, the number of harvested lymph nodes was significantly higher in the LRH group (p = 0.044). There was no difference in perioperative complications between the two groups in this study. The 5-year disease-free survival rates and overall survival rates were 91.2% and 94.0% in the LRH group and 87.8% and 95.1% in the ARH group, both respectively. Although the median residual urine volume were no statistical differences between the LRH group and the ARH group, the recovery of postoperative bladder function (uroflowmetry) in the LRH group rapidly reached presurgery levels at 1 month, and the LRH group had a smaller number of s-100 antibody stained nerves contained the parametrial sections. CONCLUSION: We demonstrated that LRH following a step-by-step procedure could achieve a higher level of prevention of damage to the bladder branch of the pelvic splanchnic nerve plexus and thus restore bladder function more rapidly.

Cancer-Specific miRNAs Extracted from Tissue-Exudative Extracellular Vesicles in Ovarian Clear Cell Carcinoma.

Ovarian clear cell carcinomas (OCCs) arise from endometriotic cysts that many women develop. Biomarkers for early OCC detection need to be identified. Extracellular vesicles have attracted attention as biomarker carriers. This study aims to identify cancer-specific miRNAs as novel OCC biomarkers using tissue-exudative extracellular vesicles (Te-EVs). Te-EVs were collected from four patients with OCC on one side and a normal ovary on the other side. Microarray analysis was performed to identify cancer-specific miRNAs in Te-EVs. Serum samples obtained before and after surgery from patients with OCC and atypical endometrial hyperplasia (AEH) (controls) were compared using real-time PCR to examine changes in the detected EV miRNA levels. Thirty-seven miRNAs were >2-fold upregulated on the OCC side compared with the normal ovarian side. We selected 17 miRNAs and created specific primers for 12 of these miRNAs. The levels of six EV miRNAs were significantly decreased in postoperative OCC serum compared to those in preoperative OCC serum. In contrast, no significant change was observed between the pre and postoperative values in the control group. We identified OCC tissue-specific miRNAs in the EVs secreted by OCC tissues. These EV miRNAs have potential for use as biomarkers for the early diagnosis and detection of OCC.

Can addition of frozen section analysis to preoperative endometrial biopsy and MRI improve identification of high-risk endometrial cancer patients?

BACKGROUND: Surgeons sometimes have difficulty determining which result to favor when preoperative results (MRI + preoperative endometrial biopsy [pre-op EB]) differ from intraoperative frozen section histology (FS) results. Investigation of how FS can complement ordinary preoperative examinations like MRI and pre-op EB in identification of patients at high risk of lymph node metastasis (high-risk patients) could provide clarity on this issue. Therefore, the aim of this study is to assess the utility of pre-op EB, MRI and FS results and determine how to combine these results in identification of high-risk patients. METHODS: The subjects were 172 patients with endometrial cancer. Patients with a histological high-grade tumor (HGT), namely, grade 3 endometrioid cancer, clear cell carcinoma or serous cell carcinoma, or with any type of cancer invading at least half of the uterine myometrium were considered high-risk. Tumors invading at least half of the uterine myometrium were classified as high-stage tumors (HST). We compared (a) detection of HGT using pre-op EB versus FS, (b) detection of HST using MRI versus FS, and (c) identification of high-risk patients using MRI + pre-op EB versus FS. Lastly, we determined to what degree addition of FS results improves identification of high-risk patients by routine MRI + pre-op EB. RESULTS: (a) Sensitivity, specificity, and accuracy for detecting HGT were 59.6, 98.4 and 87.8% for pre-op EB versus 55.3, 99.2 and 87.2% for FS (P = 0.44). (b) These figures for detecting HST were 74.4, 83.0 and 80.8% for MRI versus 46.5, 99.2 and 86.0% for FS (P < 0.001). (c) These figures for identifying high-risk patients were 78.3, 85.4 and 82.6% for MRI + pre-op EB versus 55.1, 99.0 and 81.2% for FS (P < 0.001). The high specificity of FS improved the sensitivity of MRI + pre-op EB from 78.3 to 81.2%, but this difference was not statistically significant (P < 0.16). CONCLUSION: Frozen section enables identification of high-risk patients with nearly 100% specificity. This advantage can be used to improve sensitivity for identification of high-risk patients by routine MRI + pre-op EB, although this improvement is not statistically significant.

Imaging findings of uterine adenosarcoma with sarcomatous overgrowth: two case reports, emphasizing restricted diffusion on diffusion weighted imaging.

BACKGROUND: Adenosarcoma is classified as a mixed epithelial and mesenchymal tumor composed of a benign epithelial component and a malignant stromal component. The stromal component in adenosarcoma is usually low grade, and consequently the prognosis is relatively favorable. While, adenosarcoma with sarcomatous overgrowth (SO) is defined as an adenosarcoma in which the sarcomatous component constitutes more than 25% of the tumor. The stromal component is also high-grade sarcoma showing greater nuclear pleomorphism and mitotic activity, thus, it is associated with worse prognosis. MRI findings of adenosarcoma without SO have been described in previous literatures but the imaging findings in adenosarcoma with SO may be poorly defined. Therefore we present two cases of uterine adenosarcoma with SO. CASE PRESENTATION: Patient 1 was a 76-year-old woman referred to our hospital with complaint of abdominal distension and postmenopausal bleeding. Patient 2 was a 57-year-old woman with complaint of lower abdominal pain and abnormal uterine bleeding. On magnetic resonance imaging (MRI), T2 weighted imaging showed a large, heterogeneous high-intensity mass with hyperintense tiny cysts that expanded the uterine cavity and extended into the cervical canal for both patients. On diffusion-weighted imaging (DWI), both masses appeared as high signal intensity. Patient 2 also had a right ovarian adult granulosa cell tumor that may have contributed to development of the adenosarcoma. Patient 1 recurred with peritoneal sarcomatosis 6 months after surgery and died of the disease. Patient 2 also recurred with a left upper lung metastasis 3 months after surgery. CONCLUSIONS: DWI may depict pathological changes produced by SO of adenosarcoma as high signal intensity, even though SO does not seem to change MRI findings of adenosarcoma on other sequences. Therefore, DWI could potentially predict SO in presumptive adenosarcoma on MRI and the patient's prognosis. It is also important for pathologists to know if SO can arise in adenosarcoma because they need to examine the tumor thoroughly to determine the percentage of SO component in the tumor volume when SO is present.

Prognostic significance of peritoneal cytology in low-risk endometrial cancer: comparison of laparoscopic surgery and laparotomy.

BACKGROUND: There is uncertainty surrounding the prognostic value of peritoneal cytology in low-risk endometrial cancer, especially in laparoscopic surgery. The objective of this retrospective study is to determine the prognostic significance of positive peritoneal cytology among patients with low-risk endometrial cancer and to compare it between laparoscopic surgery and conventional laparotomy. METHODS: From August 2008 to December 2019, all cases of pathologically confirmed stage IA grade 1 or 2 endometrial cancer were reviewed at Osaka Medical College. Statistical analyses used the Chi-square test and the Kaplan-Meier log rank. RESULTS: A total of 478 patients were identified: 438 with negative peritoneal cytology (232 who underwent laparotomy and 206 who undertook laparoscopic surgery) and 40 with positive peritoneal cytology (20 who underwent laparotomy and 20 who received laparoscopic surgery). Survival was significantly worse among patients with positive peritoneal cytology compared to patients with negative peritoneal cytology. However, there was no significant difference among patients with negative or positive peritoneal cytology between laparoscopic surgery and laparotomy. CONCLUSION: This retrospective study suggests that, while peritoneal cytology is an independent risk factor in patients with low-risk endometrial cancer, laparoscopic surgery does not influence the survival outcome when compared to laparotomy.

Possible prevention of post-partum depression by intake of omega-3 polyunsaturated fatty acids and its relationship with interleukin 6.

AIM: This study examined whether the intake of omega-3 polyunsaturated fatty acids (PUFA) prevented post-partum depression and if interleukin 6 (IL-6) was involved in this effect. We hypothesized that omega-3 supplementation has a protective effect against post-partum depression. METHODS: We measured eicosapentaenoic acid (EPA), the arachidonic acid (AA)/EPA ratio, and IL-6 in 80 singleton pregnant women during the first and second trimesters, and post-partum. The women also completed a dietary questionnaire, and post-partum depression was measured using the Edinburgh Postnatal Depression Scale (EPDS). We examined the correlations between the frequency of eating fish and EPA, the AA/EPA ratio and IL-6 in the first and second trimesters, and post-partum. We also investigated the correlation between the EPDS and the EPA, the AA/EPA ratio and IL-6. RESULTS: The frequency of eating fish was significantly correlated with EPA in the second trimester and post-partum and with the AA/EPA ratio in the second trimester. There was no correlation between IL-6 levels and the frequency of eating fish. Post-partum levels of EPA and the AA/EPA ratio were higher in the EPDS >7 group than in the EPDS ≤7 group. In the second trimester, a higher AA/EPA ratio was associated with EPDS >7. IL-6 levels did not differ between the two groups. CONCLUSION: In conclusion, a low dietary intake of omega-3 PUFA during pregnancy was correlated with lower EPA levels, which tended to lead to post-partum depression. The relationship between the IL-6 level and the pathogenesis of post-partum depression was unclear from the results of this study.

Outcome of in vitro fertilization cycles with automatic time-lapse instrumentation combined with the early embryo viability assessment score.

AIM: To evaluate whether embryo selection using the early embryo viability assessment (EEVA) score increases the ongoing pregnancy rate of in vitro fertilization and intracytoplasmic sperm injection patients. METHODS: One hundred eighty-one patients whose serum anti mullerian hormone (AMH) level was greater than 0.5 ng/µL were enrolled in the study. All patients received oocyte retrieval repeatedly from June 2017 to January 2019. Transferred embryos were selected using the EEVA score and Veeck's criteria. We investigated the blastocyst rate according to the EEVA score and Veeck's criteria and also evaluated the clinical outcome following embryo transfer of the blastocysts. RESULTS: Blastocyst development rate (48.7%) and high-quality blastocyst (42.4%) of Veeck 1 was statistically higher than others. The blastocyst rate (71.4%) and high-quality blastocyst rate (60.0%) for EEVA 1 was the highest, and a correlation between the EEVA score and the blastocyst rate was also identified in cases younger than 40 years. Blastocyst rate of EEVA 1 + 2 (69.8% 208/298) was statistically higher than that of Veeck 1 + 2 (40.1% 317/791) (p < 0.05) and high-quality blastocyst rate of EEVA 1 + 2 (50.0% 104/208) was also higher than that of Veeck 1 + 2 (36.6% 117/320) (p < 0.05). However, there was a significant correlation between EEVA and the pregnancy rate and pregnancy rate of EEVA 1 + 2 showed no statistical difference compared with Veeck 1 + 2. CONCLUSIONS: Although it remains to be answered whether a computer can substitute Veeck's classification, the EEVA score could be a viable alternative to predict the blastocyst rate and to select those high-potential embryos that improve the pregnancy rate.

Patient-Derived Xenograft Models in Cervical Cancer: A Systematic Review.

BACKGROUND: Patient-derived xenograft (PDX) models have been a focus of attention because they closely resemble the tumor features of patients and retain the molecular and histological features of diseases. They are promising tools for translational research. In the current systematic review, we identify publications on PDX models of cervical cancer (CC-PDX) with descriptions of main methodological characteristics and outcomes to identify the most suitable method for CC-PDX. METHODS: We searched on PubMed to identify articles reporting CC-PDX. Briefly, the main inclusion criterion for papers was description of PDX created with fragments obtained from human cervical cancer specimens, and the exclusion criterion was the creation of xenograft with established cell lines. RESULTS: After the search process, 10 studies were found and included in the systematic review. Among 98 donor patients, 61 CC-PDX were established, and the overall success rate was 62.2%. The success rate in each article ranged from 0% to 75% and was higher when using severe immunodeficient mice such as severe combined immunodeficient (SCID), nonobese diabetic (NOD) SCID, and NOD SCID gamma (NSG) mice than nude mice. Subrenal capsule implantation led to a higher engraftment rate than orthotopic and subcutaneous implantation. Fragments with a size of 1-3 mm3 were suitable for CC-PDX. No relationship was found between the engraftment rate and characteristics of the tumor and donor patient, including histology, staging, and metastasis. The latency period varied from 10 days to 12 months. Most studies showed a strong similarity in pathological and immunohistochemical features between the original tumor and the PDX model. CONCLUSION: Severe immunodeficient mice and subrenal capsule implantation led to a higher engraftment rate; however, orthotopic and subcutaneous implantation were alternatives. When using nude mice, subrenal implantation may be better. Fragments with a size of 1-3 mm3 were suitable for CC-PDX. Few reports have been published about CC-PDX; the results were not confirmed because of the small sample size.

Oncologic outcomes for patients with endometrial cancer who received minimally invasive surgery: a retrospective observational study.

BACKGROUND: Laparoscopic hysterectomy has been performed for patients with endometrial cancer as minimally invasive surgery; however, the long-term outcomes of high-risk disease compared to open surgery remain unclear. METHODS: Eight hundred and eighty-three patients with endometrial cancer who underwent laparoscopic or abdominal hysterectomy were categorized into three groups. Low-risk disease was defined as stage IA disease with endometrioid carcinoma of grade 1 or 2. Uterine-confined disease was defined as stage IA disease with high-grade tumors or stage IB and II disease. Advanced disease was defined as stage III or IV disease. The progression-free survival (PFS) and overall survival (OS) rates were compared between laparoscopic and laparotomic hysterectomy. RESULTS: Among 478 patients with low-risk disease, including 226 with laparoscopy and 252 with laparotomy, the prognosis was not significantly different between the groups (3-year PFS rate, 97.4% vs. 97.1%, p = 0.8; 3-year OS rate, 98.6% vs. 98.3%, p = 0.9). Among the 229 patients with uterine-confined disease, including 51 with laparoscopy and 178 with laparotomy, the prognosis was not significantly different between the groups (3-year PFS rate, 90.5% vs. 85.5%, p = 0.7; 3-year OS rate, 91.3% vs. 92.5%, p = 0.8). Among the 176 patients with advanced disease, including 24 with laparoscopy and 152 with laparotomy, laparoscopic hysterectomy had a higher PFS rate and OS rate than laparotomic hysterectomy (3-year PFS rate, 74.5% vs. 51.5%, p = 0.01; 3-year OS rate, 92.3% vs. 75.1%, p = 0.03). CONCLUSIONS: Laparoscopic procedures are not associated with a poorer outcome than laparotomy in patients with advanced endometrial cancer or uterine-confined endometrial cancer.

Analysis of MRI Values and Hemoglobin and Total Protein Concentrations of Cystic Ovarian Tumors.

BACKGROUND: Endometrioma generally shows higher intracystic signal intensity (SI) than mucinous cystadenoma (MCA) on T1 -weighted imaging (T1 WI). Nonendometrioma-associated malignant ovarian epithelial tumors (nonendometrioma group) often show higher intracystic SI than benign tumors on T1 WI, while the converse is true for endometrioma and endometrioma-associated malignant tumors (endometrioma group). However, it is sometimes difficult to differentiate between hemorrhagic and mucinous content based on SI on T1 WI. Hemoglobin (Hb) and protein are both speculated to shorten T1 . PURPOSE: To examine MRI values and Hb and total protein (TP) concentrations in ovarian tumors. STUDY TYPE: Prospective. SPECIMEN: In all, 182 samples from 167 cystic ovarian tumors. FIELD STRENGTH: 1.5T, spin-echo T1 WI, fast spin-echo T2 WI. ASSESSMENT: The in vivo intracystic/psoas major muscle SI ratios were determined as references for intracystic SI. T1 and T2 values, cystic content inversion times (TIs), and Hb and TP concentrations were determined to evaluate differences between 1) endometrioma and MCA; 2) benign, borderline, and malignant tumors in the nonendometrioma group; and 3) those in the endometrioma group. STATISTICAL TESTS: Wilcoxon's rank-sum test, Kruskal-Wallis test. RESULTS: In endometriomas (n = 43) and MCAs (n = 27), mean T1 and T2 (TP, Hb concentrations) were 428 and 162 msec (52.7, 12.00 g/dl) and 1639 and 600 msec (7.1, 0.06 g/dl), respectively (all, P < 0.0001). In the nonendometrioma group (epithelial benign, n = 56; borderline, n = 20; malignant, n = 25), these values were 1657 and 696 msec (6.4, 0.35 g/dl), 1235 and 400 msec (13.5, 0.83 g/dl), and 1184 and 311 msec (19.7, 0.84 g/dl), respectively (all, P < 0.0001). In the endometrioma group (endometrioma, n = 43; borderline, n = 3; malignant, n = 8), these values were 428 and 162 msec (52.7, 12.00 g/dl), 427 and 108 msec (16.6, 3.07 g/dl), and 1010 and 268 msec (24.2, 1.56 g/dl), respectively (all, P < 0.05). DATA CONCLUSION: TP and Hb concentrations were higher in the contents of endometriomas than MCAs, leading to lower T1 and T2 values. In the nonendometrioma group, TP and Hb concentrations were higher in the cystic contents of borderline and malignant tumors than benign tumors, leading to lower T1 and T2 values. Conversely, the cystic contents of borderline and malignant tumors in the endometrioma group showed lower TP and Hb concentrations compared to endometriomas, leading to higher T1 and T2 values. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:1133-1140.

Motivating Mothers to Recommend Their 20-Year-Old Daughters Receive Cervical Cancer Screening: A Randomized Study.

BACKGROUND: In Japan, the rate of cervical cancer screening is remarkably low, especially among women in their twenties and thirties, when cervical cancer is now increasing dramatically. The aim of this study was to test whether a modified government reminder for 20-year-old women to engage in cervical cancer screening, acting through maternal education and by asking for a maternal recommendation to the daughter to receive the screening, could increase their participation rate. METHODS: In two Japanese cities, 20-year-old girls who had not received their first cervical cancer screening before October of fiscal year 2014 were randomized into two study arms. One group of 1,274 received only a personalized daughter-directed reminder leaflet for cervical cancer screening. In the second group of 1,274, the daughters and their mothers received a combination package containing the same reminder leaflet as did the first group, plus an additional informational leaflet for the mother, which requested that the mother recommend that her daughter undergo cervical cancer screening. The subsequent post-reminder screening rates of these two study arms were compared. RESULTS: The cervical cancer screening rate of 20-year-old women whose mothers received the information leaflet was significantly higher than that for women who received only a leaflet for themselves (11% vs 9%, P = 0.0049). CONCLUSIONS: An intervention with mothers, by sending them a cervical cancer information leaflet with a request that they recommend that their daughter receive cervical cancer screening, significantly improved their daughters' screening rate.

The detection of sentinel lymph nodes in laparoscopic surgery can eliminate systemic lymphadenectomy for patients with early stage endometrial cancer.

BACKGROUND: The examination of a sentinel lymph node (SLN), where lymph node metastasis first occurs, may be advocated as an alternative staging technique. The aim of this study was to evaluate the feasibility and detection rates of an SLN biopsy in patients with endometrial cancer. STUDY DESIGN: Two hundred and eleven patients with endometrial cancer underwent an SLN biopsy at hysterectomy using three kinds of tracers including 99m-technetium-labeled tin colloid (99mTc), indigo carmine and indocyanine green. Factors related to the side-specific detection rate, sensitivity and false negative rate were analyzed. RESULTS: The detection rates of the SLN biopsy using 99mTc, indigo carmine and indocyanine green were 77.9, 17.0 and 73.4%, respectively. The detection rate was lower in elderly patients (≥60 years) (67.9 vs 89.2%, p < 0.01), patients with >50% myometrial invasion (68.3 vs 85.2%, p < 0.01), patients with high-grade tumors (69.5 vs 84.9%, p < 0.01) and patients who underwent laparotomy (71.2 vs 84.9%, p < 0.01). There were no significant differences in body mass index. The sensitivity was not significantly different in any factor. However, the false negative rate was higher in patients with > 50% myometrial invasion (11.5 vs 1.2%, p < 0.01), high-grade tumors (13.3 vs 0.8%, p < 0.01) and who underwent laparotomy (12.2 vs 0.4%, p < 0.01). CONCLUSION: Patients who underwent laparoscopy with < 50% myometrial invasion and low-grade tumors not only have higher detection rates, but also have lower false negative rates. These patients may avoid systemic lymphadenectomy according to the status of the SLN biopsy.

Lower FOXO3 mRNA expression in granulosa cells is involved in unexplained infertility.

AIM: The aim of this study was to investigate whether FOXO1 and FOXO3 mRNA expression in granulosa cells is the cause of unexplained infertility. METHODS: Thirty-one patients aged <40 years (13 with unexplained infertility and 18 with male partner infertility as a control group) whose serum anti-Müllerian hormone level was >0.5 ng/µL were enrolled in the study. All patients underwent oocyte retrieval under a short protocol from June 2012 to October 2013. Real-time PCR was carried out using mRNA extracted from granulosa cells retrieved from mature follicles. We compared FOXO1 and FOXO3 mRNA expression ratios in granulosa cells between the unexplained infertility group and the male infertility group. The relation between FOXO1 and FOXO3 mRNA expression ratios in granulosa cells and assisted reproduction technology clinical outcome was also examined. RESULTS: FOXO3 mRNA expression ratio was significantly lower in the unexplained infertility group than in the male infertility group. Moreover, FOXO3 mRNA expression ratio showed a positive correlation with both the number of retrieved oocytes and serum anti-Müllerian hormone level. A positive correlation was also identified between FOXO1 mRNA expression and total dose of hMG. As well, the number of retrieved oocytes in the unexplained infertility group was statistically lower than that in the male infertility group. CONCLUSION: A lower FOXO3 mRNA expression in granulosa cells leads to poor oocyte development in patients with unexplained infertility undergoing controlled ovarian stimulation for in vitro fertilization-embryo transfer.

Analyzing the risk factors for a diminished oocyte retrieval rate under controlled ovarian stimulation.

Aim: To investigate which risk factors contribute to a lower oocyte retrieval ratio in women who are receiving controlled ovarian hyperstimulation. Methods: The authors retrospectively analyzed 329 in vitro fertilization (IVF) cycles under controlled ovarian hyperstimulation by using a gonadotropin-releasing hormone antagonist or agonist at Osaka Medical College, Japan. The patients were classified into five groups: advanced age, male infertility, severe endometriosis, tubal infertility, and unexplained infertility. The primary outcomes were the patients' age, oocyte retrieval ratio, serum basal follicle-stimulating hormone, total dose of gonadotropin, and the clinical outcome. A secondary outcome was the stepwise multivariate logistic regression analysis to assess the factors associated with the failure of oocyte retrieval. Results: The oocyte retrieval ratio declined significantly with the patient's age. The ratio of endometriosis in unsuccessful cases was significantly higher than that in successful cycles. Advanced age and endometriosis were the factors that were significantly associated with a lowered oocyte retrieval rate. Conclusion: Advanced age and endometriosis are high-risk factors that contribute to oocyte retrieval failure in infertile patients who are receiving IVF treatment.

Comparison Between Laparoscopy and Laparotomy in Systematic Para-Aortic Lymphadenectomy for Patients with Endometrial Cancer: A Retrospective Multicenter Study.

Objective: Laparoscopic surgery has been developed worldwide due to its minimal invasion as well as noninferiority, compared with laparotomy. However, whether or not laparoscopic systematic para-aortic lymphadenectomy for endometrial cancer is feasible and has advantages of various clinical factors, such as a short hospital stay, less blood loss, and faster recovery, compared with open surgery has not yet been clarified. The aim of this study was to compare a laparoscopic procedure with laparotomy for para-aortic lymphadenectomy for patients with endometrial cancer. Study Design: This was a retrospective multicenter study of laparoscopic systematic para-aortic lymphadenectomy for endometrial cancer in five institutions. Materials and Methods: The current authors conducted a retrospective multicenter study of laparoscopic systematic para-aortic lymphadenectomy for endometrial cancer. The study involved patients from five institutions in Japan between January 2008 and March 2016. Clinical data were compared with those of a laparotomic procedure performed around the same period. Results: A total of 54 patients in the laparoscopic group and 99 patients in the laparotomic group were analyzed. In the laparoscopic group, 21 patients had stage IA disease, 19 had stage IB disease, 5 had stage II disease, and 9 had stage III disease. In the laparotomic group, 35 patients had stage IA disease, 19 had stage IB disease, 9 had stage II disease, and 36 had stage III disease. There were no significant differences in characteristics between the groups, including age, body mass index, and histologic type. The mean operative time in the laparoscopic group was 483 ± 102 minutes, while that in the laparotomic group was 481 ± 106 minutes (p = 0.9). The laparoscopic group had less intraoperative blood loss (143 ± 253 versus 988 ± 694 mL; p < 0.01) and shorter hospital stays (8.4 ± 5.7 versus 16.1 ± 8.0 days; p < 0.01). The rates of intraoperative complications were not significantly different between the groups. No cases of ileus occurred in the laparoscopic group. Procedures for 2 of the 54 patients in the laparoscopic group were converted to laparotomy. The number of dissected pelvic lymph nodes (31.8 ± 10.1 versus 39.9 ± 15.9, p < 0.01) and para-aortic lymph nodes (26.2 ± 10.9 versus 31.1 ± 13.2; p = 0.02) were lower in the laparoscopic group than in the laparotomic group. The postoperative minimum level of hemoglobin was higher in the laparoscopic group than in the laparotomic group (10.4 ± 1.1 g/dL versus 9.9 ± 1.4 g/dL; p = 0.02). In contrast, the postoperative maximum level of C-reactive protein was lower in the laparoscopic group than in the laparotomic group (6.3 ± 3.8 mg/dL versus 10.2 ± 4.9 mg/dL; p < 0.01). The recurrence rate was not significantly different between the groups in the above time period (7.4% versus 14.3%; p = 0.2). Conclusions: Laparoscopic systematic para-aortic lymphadenectomy is feasible and can be substituted for laparotomic procedures for patients with early stage endometrial cancer. ( J GYNECOL SURG 33:105).

Mothers' attitudes in Japan regarding cervical cancer screening correlates with intention to recommend cervical cancer screening for daughters.

BACKGROUND: Cervical cancer and its precancerous lesions caused by human papilloma virus (HPV) are steadily increasing in women in Japan. In comparison with women in other resource-rich countries, young women in Japan have a dismally low screening rate for cervical cancer. Our preliminary research has shown that 20-year-old women in Japan usually ask their mothers for advice regarding their initial cervical cancer screening. The objective of our current research is to determine the social factors among mothers in Japan that are causing them to give advice to their daughters regarding the HPV vaccine and cervical cancer screening. METHODS: The survey's targets were mothers who had 20-year-old daughters. We recruited respondents from the roster of a commercial internet survey panel. We analyzed for correlations between a mother's knowledge concerning cervical cancer, her recent cancer screening history, and the advice she gave to her daughter regarding cervical cancer screening. RESULTS: We obtained 618 valid answers to the survey. Compared with mothers who did not get screening, mothers who had cervical cancer screening had significantly more knowledge about cervical cancer and its screening (p < 0.05). The daughters of mothers with recent screening had received HPV vaccination more often than those of mothers without recent screening (p = 0.018). Mothers with recent screening histories tended more often to encourage their daughters to have cervical cancer screening (p < 0.05). When mothers were properly educated concerning cervical cancer and its screening, they were significantly more likely than before to recommend that their daughters have it (p < 0.0001). CONCLUSIONS: In young Japanese women, given the important role their mothers have in their lives, it is probable that we could improve their cervical cancer screening rate significantly by giving their mothers better medical information, and a chance to experience cervical cancer screening for themselves.

Development of an efficient strategy to improve HPV immunization coverage in Japan.

BACKGROUND: In Japan, new HPV immunizations have dropped dramatically after repeated adverse media reports and a June 2013 temporary suspension of the government's recommendation for the vaccine. The aim of the present study was to develop an efficient strategy to improve HPV immunization coverage across Japan. METHODS: We conducted an internet survey in Japan of mothers of 12-16 year-old girls who were unvaccinated as of May, 2015. The goal was to gather behavioral information from the mothers to develop a strategy for improving Japanese HPV immunization coverage. RESULTS: Valid survey answers were obtained from 2060 mothers. The survey found that a hypothetical restart of a governmental recommendation for the vaccine would induce 4.1 % of all the mothers surveyed to be more likely to encourage vaccination of their daughters, without any other preconditions. This initial result would be followed by a moderate spread of vaccinations to these daughters' close friends and acquaintances, hypothetically resulting in a total vaccination rate of 21.0 % of the targeted age-eligible girls. As a second critical step for improving vaccinations, an educational information sheet integrating the concepts of behavioral economics for changing behaviors was found to be significantly effective for persuading mothers with poorer decision-making facilities, who would otherwise prefer to wait to first see the vaccination of other girls of the same age as their daughter. CONCLUSIONS: Following what we foresee as the inevitable restart of the Japanese government's recommendation for receiving the HPV vaccine, we expect to first see vaccinations occurring in a very small group of girls, the daughters of the most willing mothers, which will be roughly 4 % of those eligible for government paid vaccinations. This will be followed by the spread of vaccinations outward through these girls' circle of friends and acquaintances, and, finally, to the daughters of the most skeptical mothers, those who would await the return of new vaccine safety results from a large group of similarly-aged girls. As a critical step in improving HPV vaccine coverage in Japan, an educational information sheet that integrates the concepts of behavioral economics for changing behaviors can be employed to persuade mothers with poor decision-making facilities.