Performance of an ancillary test for cervical cancer that measures miRNAs and cytokines in serum and cervical mucus.

Currently, human papillomavirus tests and cytology are used to screen for cervical cancer. However, more accurate ancillary screening tests are needed. MicroRNAs (miRNAs) and cytokines are promising biomarkers that are aberrantly expressed in cervical cancer. Therefore, the potential of developing new screening markers based on the levels of miRNAs and cytokines in serum and local mucus samples from the same patients with cervical neoplasia was investigated. miRNA screening was performed by microarray and measurement using real-time reverse-transcriptase PCR. Cytokine were measured using multiplex bead assay, and changes in expressions were analyzed based on disease severity. As lesions progressed, miR-20b-5p, -155-5p, -144-3p, -451a, and -126-3p expression levels were increased in mucus, and miR-16-5p, -223-3p, and -451a expression levels were decreased in serum. Regarding cytokines, IL-6, IL-8, monocyte chemoattractant protein-1, Eotaxin, interferon-γ, and RANTES were increased, whereas granulocyte-colony-stimulating factor (G-CSF) was significantly decreased in mucus. miRNAs and cytokines in serum did not have high diagnostic accuracy. However, a combination of miR-20b-5p, -451a, -126-3p, Eotaxin, as well as G-CSF in mucus samples, had high diagnostic accuracy with an area under the receiver operating characteristic curve of 0.989 (0.979-0.999). Our results suggest that using mucus for this ancillary test is more beneficial than serum.

Intrauterine manipulator use during laparoscopic hysterectomy for endometrial cancer: association for pathological factors and oncologic outcomes.

OBJECTIVE: To examine the association between intrauterine manipulator use and pathological factors and oncologic outcomes in patients with endometrial cancer who had laparoscopic hysterectomy in Japan. METHODS: This was a nationwide retrospective cohort study of the tumor registry of the Japan Society of Obstetrics and Gynecology. Study population was 3846 patients who had laparoscopic hysterectomy for endometrial cancer from January 2015 to December 2017. An automated 1-to-1 propensity score matching with preoperative and intraoperative demographics was performed to assess postoperative pathological factors associated with the intrauterine manipulator. Survival outcomes were assessed by accounting for possible pathological mediators related to intrauterine manipulator use. RESULTS: Most patients had preoperative stage I disease (96.5%) and grade 1-2 endometrioid tumors (81.9%). During the study period, 1607 (41.8%) patients had intrauterine manipulator use and 2239 (58.2%) patients did not. In the matched cohort, the incidences of lymphovascular space invasion in the hysterectomy specimen were 17.8% in the intrauterine manipulator group and 13.3% in the non-manipulator group. Intrauterine manipulator use was associated with a 35% increased odds of lymphovascular space invasion (adjusted odds ratio 1.35, 95% confidence interval (CI) 1.08 to 1.69). The incidences of malignant cells identified in the pelvic peritoneal cytologic sample at hysterectomy were 10.8% for the intrauterine manipulator group and 6.4% for the non-manipulator group. Intrauterine manipulator use was associated with a 77% increased odds of malignant peritoneal cytology (adjusted odds ratio 1.77, 95% Cl 1.29 to 2.31). The 5 year overall survival rates were 94.2% for the intrauterine manipulator group and 96.6% for the non-manipulator group (hazard ratio (HR) 1.64, 95% Cl 1.12 to 2.39). Possible pathological mediators accounted HR was 1.36 (95%Cl 0.93 to 2.00). CONCLUSION: This nationwide analysis of predominantly early stage, low-grade endometrial cancer in Japan suggested that intrauterine manipulator use during laparoscopic hysterectomy for endometrial cancer may be associated with an increased risk of lymphovascular space invasion and malignant peritoneal cytology. Possible mediator effects of intrauterine manipulator use on survival warrant further investigation, especially with a prospective setting.

Guideline for gynecological practice in Japan: Japan Society of Obstetrics and Gynecology and Japan Association of Obstetricians and Gynecologists 2023 edition.

Twelve years after the first edition of The Guideline for Gynecological Practice, which was jointly edited by The Japan Society of Obstetrics and Gynecology and The Japan Association of Obstetricians and Gynecologists, the 5th Revised Edition was published in 2023. The 2023 Guidelines includes 5 additional clinical questions (CQs), which brings the total to 103 CQ (12 on infectious disease, 30 on oncology and benign tumors, 29 on endocrinology and infertility and 32 on healthcare for women). Currently, a consensus has been reached on the Guidelines, and therefore, the objective of this report is to present the general policies regarding diagnostic and treatment methods used in standard gynecological outpatient care that are considered appropriate. At the end of each answer, the corresponding Recommendation Level (A, B, C) is indicated.

Metabolomic and microbiome analysis of cervicovaginal mucus in in vitro fertilization-embryo transfer: Toward predicting pregnancy success.

Purpose: In the context of in vitro fertilization-embryo transfer (IVF-ET), factors other than egg quality may be key determinants of treatment success, in particular, maternal factors related to uterine endometrial receptivity and unidentified factors. We therefore aimed to analyze the metabolome and microbiome in IVF-ET patients who did and did not achieve pregnancy. Methods: Cervicovaginal mucus was collected from patients undergoing IVF-ET. Metabolite analysis was conducted by liquid chromatography-mass spectrometry and the microbiota were determined by the polymerase chain reaction using universal 16S-rRNA gene bacterial primers by MiSeq sequencing. Patients were classified as pregnant (N = 10) or nonpregnant (N = 13). Metabolic pathways were examined by MetaboAnalyst. Results: Three metabolic pathways, including alanine-aspartate-glutamate metabolism, arginine biosynthesis, and cysteine-methionine metabolism, were commonly decreased at the time of embryo transfer irrespective pregnant outcomes. Notably, pyruvate was decreased in the pregnant group. Amino acid metabolites showed inverse correlations with the presence of anaerobic microbiota in the nonpregnant group. Conclusions: Metabolism decreased during embryo transplantation, with a notable decrease in pyruvate metabolism, particularly in patients who became pregnant. The behavior of metabolites in the pregnant and nonpregnant groups suggests that metabolome analysis in the cervicovaginal mucus may be a diagnostic marker for predicting pregnancy.

Human papillomavirus vaccine impact on invasive cervical cancer in Japan: Preliminary results from cancer statistics and the MINT study.

The first prophylactic vaccine against human papillomavirus (HPV) 16 and HPV18 was licensed in Japan in 2009. HPV vaccine effectiveness against high-grade cervical lesions has been demonstrated among young Japanese women, but evidence of its effects on invasive cervical cancer (ICC) is lacking. Using data from two different cancer registries, we compared recent trends of new ICC cases by age group using Poisson regression analysis. We also analyzed time trends in HPV16/18 prevalence among 1414 Japanese women aged <40 years newly diagnosed with ICC in the past decade. Based on the population-based cancer registry, the incidence of ICC among young women aged 20-29 years showed a significant decline from 3.6 to 2.8 per 100 000 women-years during 2016-2019, but no similar decline was observed for older age groups (p < 0.01). Similarly, using data from the gynecological cancer registry of the Japan Society of Obstetrics and Gynecology, the annual number of ICCs among women aged 20-29 years also decreased from 256 cases to 135 cases during 2011-2020 (p < 0.0001). Furthermore, a declining trend in HPV16/18 prevalence in ICC was observed only among women aged 20-29 years during 2017-2022 (90.5%-64.7%, p = 0.05; Cochran-Armitage trend test). This is the first report to suggest population-level effects of HPV vaccination on ICC in Japan. Although the declining trend in HPV16/18 prevalence among young women with ICC supports a causal linkage between vaccination and results from cancer registries, further studies are warranted to confirm that our findings are attributable to vaccination.

Questionnaire survey regarding current status of minimally invasive surgery for endometrial cancer in Japan: A cross-sectional survey for JSGOE members.

AIM: Minimally invasive surgery (MIS) has been introduced as an alternative to more radical surgical procedures. The Japan Society of Gynecologic and Obstetric Endoscopy and Minimally Invasive Therapy conducted a cross-sectional questionnaire survey to ascertain the status of MIS for endometrial cancer. METHODS: The survey was conducted between May 10 and June 30, 2022. The questionnaire included information on personal attributes, academic affiliations, qualifications, hysterectomies, and intraoperative procedures performed. RESULTS: The total number of questionnaire respondents was 436 (9.2% of the membership). The hysterectomy methods and percentage performed were as follows: simple total hysterectomy (equivalent to benign surgery), 3%; simple total hysterectomy with care to avoid shaving the cervix, 31%; extended total hysterectomy, 48%; and modified radical hysterectomy, 15%. An analysis of hysterectomies performed using MIS for endometrial cancer by qualified gynecologists of endoscopy or board-certified gynecologic oncologists showed a tendency not to choose simple total hysterectomy compared to the gynecologists who did not hold certification (p = 0.019, p = 0.045, and p = 0.010, respectively). Additionally, 67% of respondents did not use uterine manipulators, and 59% of the respondents did not perform lymph node dissection following the guidelines for treating endometrial cancer in Japan. CONCLUSION: This study provided the current status of MIS for endometrial cancer in Japan. The hysterectomy method, use of uterine manipulators, and criteria for omitting lymph node dissection were generally in agreement with the guidelines. Currently, an extra-fascial simple hysterectomy, including at least not shaving the cervix, was a major method for early invasive endometrial cancer using MIS.

Lower accuracy of cytological screening for high-grade squamous intraepithelial neoplasia in women over 50 years of age in Japan.

BACKGROUND: As the population ages in developed countries, the number of Pap smears for cervical cancer screening of older women is increasing. There is concern that cervical atrophy may cause misinterpretation of results for this segment of the population. The present study evaluated the accuracy of screening for high-grade intraepithelial lesions (HSILs) in women younger or older than 50 years, to determine whether aging affects cytological interpretation. METHODS: Patients with HSIL cytology (N = 1565) were dichotomized into those aged 20-49 years or aged ≥ 50 years. Association between histology results and age was examined. Pearson's chi-squared test and Cochran-Armitage trend test were used for statistical analysis. RESULTS: The positive predictive value (PPV) for cervical intraepithelial neoplasia (CIN)2 and worse was 65.2% (62/95) in older women but 87.3% (482/552) in younger women (p < 0.001). Older patients had a significantly lower PPV (p = 1.69 × 10-8). Separately analyzing chronic cervicitis, CIN1 and overt cancer grouped together, compared with another group composed of CIN2 and CIN3, we found that the PPV for CIN2 and CIN3 was lower in older than in younger women [44.2% (42/95)-vs-82.4% (455/552), p < 0.001], respectively. CONCLUSIONS: HSILs are associated with a wide range of disease categories as age increases, and the accuracy of HSIL interpretation is lower in older women.

A New Species of Sea Whip Gorgonian-Associated Zoantharian (Cnidaria: Anthozoa: Hexacorallia: Parazoanthidae) from the Ryukyu Islands, Japan, with Subgeneric Subdivision of Genus Umimayanthus.

Symbioses between invertebrates are common in the ocean although usually the diversity and specificity of their interactions are not well understood. Parazoanthidae (Cnidaria: Anthozoa: Zoantharia) is one of the most diverse zoantharian families in terms of numbers of genera and species. Species in this family are commonly associated with various other invertebrates that they utilize as their substrate. Previous studies have re-organized the taxonomy of Parazoanthidae and revealed a strong specificity between many parazoanthid species and genera and their substrates. However, our understanding of the species diversity of Parazoanthidae is far from complete, as parazoanthids are often overlooked in sampling surveys. In this study, we establish three subgenera under the genus Umimayanthus Montenegro, Sinniger, and Reimer, 2015; the nominotypical Umimayanthus, Paraumimayanthus subgen nov., and Gorgoniazoanthus subgen. nov., based on the finding of a new species, Umimayanthus (Gorgoniazoanthus) kanabou sp. nov., associated with the sea-whip gorgonian Ellisella sp. from approximately 30 m depth in shallow mesophotic coral reef communities in Oura Bay on Okinawajima Island and in Oshima Strait near Amami-Oshima Island, in the Ryukyu Islands, southern Japan. We additionally report on gastropods and crustaceans observed in association with U. kanabou, and these species are thought to potentially prey upon the zoantharians or on gorgonian polyps. Umimayanthus kanabou is phylogenetically closely related to congeneric sponge-associated Umimayanthus spp., further supporting the recent hypothesis that substrate preferences may change during the evolutionary history of zoantharians.

Surveillance of radical hysterectomy for early-stage cervical cancer in the early experienced period of minimally invasive surgery in Japan.

OBJECTIVE: The purpose of our study was to conduct a detailed survey of radical hysterectomy in Japanese patients with early-stage cervical cancer, and to compare oncologic outcomes between open and minimally invasive radical hysterectomy. METHODS: In Japan during 2015, the medical records of 929 patients with FIGO stage IB1 and IIA disease treated with radical hysterectomy were retrospectively reviewed. We assessed patients' characteristics, disease-free survival (DFS), overall survival (OS) and prognostic factors for survival. RESULTS: The median patient age was 44 (20-80) years. Most patients (94.4%) had stage IB1 disease. Of the patients who underwent radical hysterectomy, 91.2% underwent open surgery and 8.8% underwent minimally invasive surgery (MIS). The median follow-up period was 40.8 months (range, 0.49-51.1 months). The rate of DFS and OS at 4 years in all patients was 88.3% and 96.4%, respectively. Multivariate analysis identified age (≥ 47), adenocarcinoma histology, tumor size (≥ 2 cm), parametrial invasion, positive lymph node metastasis and institutional accreditation as independent predictors of recurrence, and adenocarcinoma, other cell types, and positive lymph node metastasis as independent predictors of death. Oncologic outcomes in all patients were similar between open and MIS, including DFS and OS. CONCLUSION: The survival rate of the Japanese patients underwent radical hysterectomy for early-stage cervical cancer was favorable. No significant differences were observed for DFS and OS between open and MIS performed by a limited number of surgeons at a limited number of facilities in Japan. Further investigations are required to identify the appropriate patients might benefit from MIS.

Guideline for Gynecological Practice in Japan: Japan Society of Obstetrics and Gynecology and Japan Association of Obstetricians and Gynecologists 2020 edition.

Nine years after the first edition of The Guideline for Gynecological Practice, which was jointly edited by The Japan Society of Obstetrics and Gynecology and The Japan Association of Obstetricians and Gynecologists, the 4th Revised Edition was published in 2020. The 2020 Guidelines includes 4 additional clinical questions (CQ), which brings the total to 99 CQ (12 on infectious disease, 29 on oncology and benign tumors, 29 on endocrinology and infertility and 29 on healthcare for women). Currently, a consensus has been reached on the Guidelines, and therefore, the objective of this report is to present the general policies regarding diagnostic and treatment methods used in standard gynecological outpatient care that are considered appropriate. At the end of each answer, the corresponding Recommendation Level (A, B, C) is indicated.

Effect of Obesity on Hematotoxicity Induced by Carboplatin and Paclitaxel Combination Therapy in Patients with Gynecological Cancer.

Despite in vivo studies suggesting that obesity increases carboplatin (CBDCA) bone marrow toxicity, the American Society of Clinical Oncology recommends that full weight-based cytotoxic chemotherapy doses be used to treat obese patients with cancer. Accordingly, the present study retrospectively investigated the effect of body mass index (BMI) on bone marrow toxicity in patients with gynecological cancer who underwent paclitaxel and carboplatin (TC) therapy after eliminating the effect of the target area under the curve (AUC). Risk factors for CBDCA bone marrow toxicity were also identified. A total of 110 patients with primary gynecological cancer or gynecological cancer of unknown primary origin who underwent TC therapy with a target AUC of 5-6 were included herein. Patients with a BMI of ≥25 and <25 kg/m2 were assigned to the obesity and control groups, respectively, and evaluated according to changes in hematological test values (platelet, white blood cell, and hemoglobin counts) starting from initial TC therapy administration until 21 d after the second treatment course. The obesity group had a significantly higher thrombocytopenia rate than the control group. Risk factors for thrombocytopenia ≥ grade 2 included BMI ≥25 kg/m2. Among patients with primary gynecological cancer or gynecological cancer of unknown primary origin who had a BMI of ≥25 kg/m2, those receiving CBDCA may be at increased risk for thrombocytopenia ≥ grade 2 when the dosage is calculated using the Calvert formula with the creatinine clearance level.

Phylogenetic relationships among the clownfish-hosting sea anemones.

The clownfish-sea anemone symbiosis has been a model system for understanding fundamental evolutionary and ecological processes. However, our evolutionary understanding of this symbiosis comes entirely from studies of clownfishes. A holistic understanding of a model mutualism requires systematic, biogeographic, and phylogenetic insight into both partners. Here, we conduct the largest phylogenetic analysis of sea anemones (Order Actiniaria) to date, with a focus on expanding the biogeographic and taxonomic sampling of the 10 nominal clownfish-hosting species. Using a combination of mtDNA and nuDNA loci we test (1) the monophyly of each clownfish-hosting family and genus, (2) the current anemone taxonomy that suggests symbioses with clownfishes evolved multiple times within Actiniaria, and (3) whether, like the clownfishes, there is evidence that host anemones have a Coral Triangle biogeographic origin. Our phylogenetic reconstruction demonstrates widespread poly- and para-phyly at the family and genus level, particularly within the family Stichodactylidae and genus Stichodactyla, and suggests that symbioses with clownfishes evolved minimally three times within sea anemones. We further recover evidence for a Tethyan biogeographic origin for some clades. Our data provide the first evidence that clownfish and some sea anemone hosts have different biogeographic origins, and that there may be cryptic species of host anemones. Finally, our findings reflect the need for a major taxonomic revision of the clownfish-hosting sea anemones.

Cytokine expression profiles in cervical mucus from patients with cervical cancer and its precursor lesions.

Human papillomavirus (HPV) infection can persist in the cervical epithelium without provoking a strong host immune response, leading to the development of cervical cancer. Cytokines, which mediate innate and adaptive immune activities, are secreted in the cervical mucus; however, there is currently no appropriate method for assessing cytokine levels in mucus specimens. Here, we employed multiplexed bead-based immunoassays to examine cytokine levels in cervical mucus using both weighted-volume and total protein concentration methods to adjust for different specimen volumes in individual patients. Out of 18 cytokines initially examined in the primary cohort patient group (n = 28), 14 were detected in more than 10% of the samples. Of these 14 cytokines, expression levels of interferon (IFN)-γ, granulocyte-macrophage colony-stimulating factor (GM-CSF), RANTES, and eotaxin were significantly increased with the disease severity in the secondary cohort patient group (n = 235). We also examined associations between cytokine levels and clinical parameters, such as cytology and HPV genotype. Of the 14 cytokines, granulocyte colony-stimulating factor (G-CSF) was downregulated in HPV-positive specimens. Examination of co-expression patterns of cytokines in relation to HPV infection status revealed that several pairs of cytokines were simultaneously upregulated in HPV-positive cases, including INF-γ and interleukin (IL)-17A, GM-CSF and monocyte chemoattractant protein-1 (MCP-1), GM-CSF and RANTES, IL-17A and RANTES, and MCP-1 and eotaxin. Interestingly, upregulation of GM-CSF and RANTES might reflect a shift in immuno-regulatory cytokines in HPV-positive specimens, potentially associated with more severe cervical neoplasia.

Redescription of Synactinernus flavus for the First Time after a Century and Description of Synactinernus churaumi sp. nov. (Cnidaria: Anthozoa: Actiniaria).

Two species of Synactinernus sea anemones were found in Japanese waters. Synactinernus flavus Carlgren, 1918, the only described species of this genus, is rediscovered from off the Goto Islands a century after the original description. Synactinernus flavus was once synonymized with Isactinernus quadrilobatus Carlgren, 1918; however, we show that, based on morphological (including examination of type specimens) and molecular (using nuclear 18S rDNA) evidence, these species are completely different. The other species, Synactinernus churaumi sp. nov., was found off Ishigaki Island and Okinawa Island by a remotely operated vehicle (ROV), and had been kept for 15 years in a tank at the Okinawa Churaumi Aquarium. There are clear differences between these two species; therefore, we describe the second species and revise the diagnosis of Synactinernus.

A case of uterine lymphangioleiomyomatosis in a young woman that was identified via peritonitis.

Although lymphangioleiomyomatosis is often observed with tuberous sclerosis, uterine lymphangioleiomyomatosis is rare. Our patient was 36 years old (gravida 0, para 0). She had a history of tuberous sclerosis, and many myometrial cystic lesions were identified during assisted reproductive therapy. Although we administered a gonadotropin-releasing hormone analog, myometrial cystic lesions increased in size. Therefore, simple hysterectomy, bilateral salpingo-oophorectomy and pelvic lymph node biopsy were performed. Postoperative histology showed lymphangioleiomyomatosis and myometrial abscess. For uterine lesions in young women with tuberous sclerosis, the possibility of uterine lymphangioleiomyomatosis should also be considered.

Guidelines for office gynecology in Japan: Japan Society of Obstetrics and Gynecology (JSOG) and Japan Association of Obstetricians and Gynecologists (JAOG) 2017 edition.

Six years after the first edition of The Guideline for Gynecological Practice, which was jointly edited by The Japan Society of Obstetrics and Gynecology and The Japan Association of Obstetricians and Gynecologists, the third revised edition was published in 2017. The 2017 Guidelines includes 10 additional clinical questions (CQ), which brings the total to 95 CQ (12 on infectious disease, 28 on oncology and benign tumors, 27 on endocrinology and infertility and 28 on healthcare for women). Currently a consensus has been reached on the Guidelines and therefore the objective of this report is to present the general policies regarding diagnostic and treatment methods used in standard gynecological outpatient care that are considered appropriate. At the end of each answer, the corresponding recommendation level (A, B, C) is indicated.

Potential role for nectin-4 in the pathogenesis of pre-eclampsia: a molecular genetic study.

BACKGROUND: Nectins are cell adhesion molecules that play a pivotal role in adherens junctions and tight junctions. Our previous study using whole-genome oligonucleotide microarrays revealed that nectin-4 was upregulated in pre-eclamptic placentas. We investigated the role of nectin-4 in the etiology of pre-eclampsia. METHODS: We investigated the expression of nectin-4 using real-time RT-PCR, western blot and immunostaining. Additionally, we performed matrigel invasion assay and cytotoxicity assay using cells overexpressing the nectin-4. RESULTS: NECTIN4 transcripts were elevated in pre-eclamptic placentas relative to uncomplicated pregnancies. Nectin-4 protein levels in pre-eclamptic placentas were higher on a semi-quantitative western blot. Nectin-4 was localized at the apical cell membrane in syncytiotrophoblast cells and not at the adherens junctions. Nectin-4 was also detected in cytotrophoblasts and a subset of cells in the decidua. Nectin-4 overexpressing trophoblast cells migrated normally in the matrix. However, Natural killer (NK) cells showed a strong cytotoxic effect against nectin-4 overexpressing trophoblast cells. No causative genetic variation was evident in the NECTIN4 gene from a pre-eclamptic placenta. CONCLUSIONS: There are as yet unknown factors that induce nectin-4 overexpression in trophoblast cells that may contribute to abnormal placentation via an aberrant immune response and the onset of a pre-eclamptic pregnancy.

Comparison of methods using paraffin-embedded tissues and exfoliated cervical cells to evaluate human papillomavirus genotype attribution.

Monitoring the attribution of human papillomavirus (HPV) genotypes to cervical precancerous lesions is essential in assessing the efficacy of HPV vaccines. To resolve the lack of studies comparing the HPV genotyping procedures used to estimate HPV genotype attribution, we undertook a retrospective cross-sectional study to determine the appropriate genotyping procedures for evaluating the potential efficacy of HPV vaccines. Three procedures, including two different genotyping methods, Clinichip HPV test (C-Chip) and modified GP5+/6+ PCR coupled to fluorescent bead sorter detection (MGP), using exfoliated cervical cells (C-Chip and C-MGP, respectively) or formalin-fixed paraffin-embedded tissues (F-MGP), were compared. The overall agreement in detecting high-risk HPV was 88.5-92.1% among the three procedures, and genotype-specific agreement was 83.9-100% for all pairwise comparisons. In cervical intraepithelial neoplasia grade 2/3 specimens, HPV16/18 attribution estimated with the hierarchical attribution method was consistent among the procedures: 52.3% (45/86) for C-Chip, 54.7% (47/86) for C-MGP, and 52.3% (45/86) for F-MGP (P = 0.81). HPV16/18/31/33/45/52/58 hierarchical attribution was 88.4% (76/86) with C-Chip, 86.0% (74/86) with C-MGP, and 83.7% (72/86) with F-MGP (P = 0.49). In cervical intraepithelial neoplasia grade 3 specimens, the corresponding hierarchical attribution was 96.4% (53/55) with C-Chip, 89.1% (49/55) with C-MGP, and 94.5% (52/55) with F-MGP (P = 0.27). Although F-MGP is theoretically a reliable method for determining HPV genotype attribution, it is acceptable to use C-Chip or C-MGP, coupled to the hierarchical attribution formula to correct the bias of multiple infections. These approaches using exfoliated cervical cells are practical for monitoring the efficacy of HPV vaccines.

Pregnancy Outcomes After Abdominal Radical Trachelectomy for Early-Stage Cervical Cancer: A 13-Year Experience in a Single Tertiary-Care Center.

OBJECTIVE: To investigate pregnancy outcomes in women after abdominal radical trachelectomy (RT) for early-stage cervical cancer. METHODS: The patients' background, fertility, and pregnancy outcomes were reviewed in a total of 61 pregnancies in 48 of 172 women who underwent abdominal RT at Keio University Hospital between September 2002 and December 2013. RESULTS: There were 5 women with stage IA1, 2 with stage IA2, and 41 with stage IB1. Histological types were as follows: squamous cell carcinoma (n = 36), adenocarcinoma (n = 10), and adenosquamous cell carcinoma (n = 2). The pregnancy rate of women attempting to conceive after abdominal RT was 44% (48/109). The mean ± SD duration from abdominal RT to conception was 3.1 ± 1.9 years. Of 61 pregnancies, 42 pregnancies were achieved by fertility treatment (in vitro fertilization-embryo transfer, 39; intrauterine insemination, 3). After excluding one pregnancy without detailed clinical information, there were 42 live births (5 in 22-27 weeks, 11 in 28-33weeks, 20 in 34-36 weeks, and 6 in 37-38 weeks), 13 miscarriages, and 5 ongoing pregnancies. While there were 10 first trimester miscarriages, 3 pregnancies ended in the second trimester owing to chorioamnionitis. The mean gestational age at birth was 33 weeks of pregnancy. Thirty-seven neonates were appropriate-for-date, and one was small-for-date. Six pregnancies exhibited massive bleeding from the residual cervix in the late pregnancy. Preterm birth less than 34 weeks of pregnancy was related to premature rupture of the membrane (P < 0.05). Chorioamnionitis was evident in 9 of 11 pregnancies with preterm premature rupture of the membrane followed by birth at less than 34 weeks of pregnancy. No parturients exhibited lochiometra and endometritis postpartum. CONCLUSIONS: Abdominal RT provided favorable pregnancy outcomes, and fertility treatment could be advantageous to conception. Massive bleeding from the residual cervix as well as ascending infection might be characteristic features during pregnancy after abdominal RT.

Changing state of gynecologic oncologist specialty in Japan.

Gynecologic oncologists must have extensive knowledge regarding the methods of treating a diverse range of gynecologic cancers as well as the ability to perform cutting-edge multidisciplinary treatments that frequently involve surgery. Given that coordination with other medical departments is vital for treatment, a high level of interpersonal and technical skills needs to be demonstrated to form the axis for medical treatment. One objective of the specialist certification system is the grooming of leaders as gynecologic oncologists while instructing trainees. The most distinguishing feature of Japanese gynecologic oncologists is that they need experience in more than 150 invasive cancer treatments, including more than 100 operations within the last 3-5 years. As for performance of surgery, at least 30 operations, including 15 radical hysterectomies, are required. Since surgical methods, including laparoscopic surgery, are undergoing a radical change, and increasing numbers of patients are undergoing radiotherapy for invasive cervical cancer, a review of the necessary requirements is critical. It is important to foster new leaders who are research-oriented. Now is the time for marked reform with the new specialist certification system being introduced by the Japanese Medical Specialty Board. Japan has the advantage of offering medical services at a much lower cost because of its national health insurance system. However, specialists are currently not receiving clear benefits befitting their efforts, and the question of how to maintain their motivation is an issue for the future. For these purposes, I believe securing incentives is a critical issue for specialists.