Nuclear morphometry as an adjunct to cytopathologic examination of endometrial brushings on LBC samples: A prospective approach to combined evaluation in endometrial neoplasms and look alikes.

OBJECTIVE: In this study, we aimed to retrospectively investigate and confirm whether atypical nuclear findings in endometrial cytology are useful when assessed by image morphometry in liquid-based cytology (LBC) and compared with microscopic evaluation. METHODS: In total, 53 cases were selected for this study, including 11 presenting proliferative endometrium, 12 with surface papillary syncytial change with endometrial glandular and stromal breakdown (EGBD-SPSC), 10 endometrioid carcinoma grade 1 (G1-EEC), 10 EEC grade 3 (G3-EEC), and 10 endometrial serous carcinomas (ESC). Nuclear image morphometry for nuclear geometric features (area, grey value, aspect ratio, internuclear distance, nucleolar diameter) was performed using ImageJ computer software. For assessing nucleoli, 3861 nuclei were measured, and for nuclear findings, except for nucleoli, 4036 nuclei were measured in total. RESULTS: (a) Compared with G1-EEC, G3-EEC and ESC presented a marked increase in all six parameters (nuclear enlargement, anisonucleosis, nuclear shade, nuclear shape, irregularity of nuclear arrangement, and nucleolar size). (b) EGBD-SPSC presented a marked increase in two parameters (nuclear shade, nuclear shape) when compared with G1/G3-EEC and ESC. (c) Compared with EGBD-SPSC, EEC and ESC demonstrated a marked increase in nucleolar size (≥2.0 µm). (d) ESC presented a marked increase in nucleolar size (≥3.0 µm) when compared with G3-EEC. CONCLUSIONS: Here we confirmed that atypical nuclear findings evaluated by image morphometry are as useful as microscopic evaluations in endometrial cytology. We believe that the objective evaluation of nucleolar size could contribute to an accurate diagnosis of endometrial-LBC samples.

Insulin-like growth factor-II mRNA-binding protein 3 immunocytochemical expression in direct endometrial brushings: Possible diagnostic help in endometrial cytology.

INTRODUCTION: This study evaluated the immunocytochemical (ICC) expression of IMP3 in direct endometrial brushings processed as liquid-based cytology (LBC) samples of endometrioid adenocarcinoma (EAC), serous carcinoma (ESC) and surface papillary syncytial change (SPSC) with endometrial glandular and stromal breakdown (EGBD) to exploit its possible differential diagnostic aid. METHODS: In total, 333 samples of LBC samples were obtained from selected outpatients in parallel with Pipelle endometrial sampling. They consisted of 97 EAC (83 grade 1: EAC-1, 14 EAC-3), 35 ESC and 201 benign endometrial samples (51 proliferative, 42 secretory, 38 atrophic, 70 SPSC with EGBD). ICC expression of insulin-like growth factor-II mRNA-binding protein 3 (IMP3) was manually performed on Papanicolaou-stained LBC samples. RESULTS: The ESC samples showed positive staining cells in 100%, EAC-3 in 28.5%, and EAC-1 in 2.4% cases. All the benign endometrium samples were negative. Only ESC cases showed strong immunoreactivity (≥3+) in more than 50% of tumour cells with an average frequency of 80%. CONCLUSIONS: IMP3 is a helpful immunomarker to distinguish ESC from EAC and SPSC in endometrial cytology.

Evaluation of cellular adequacy in endometrial liquid-based cytology.

OBJECTIVE: This study evaluated cellular adequacy in endometrial liquid-based cytology (LBC) specimens. METHODS: In total, 1267 cases were obtained and the rate of unsatisfactory specimen and diagnostic accuracy for malignancy were assessed. If ≥10 cellular clusters composed of ≤30 endometrial cells were found per specimen, then the sample was provisionally considered adequate. RESULTS: The unsatisfactory rate (with fewer than 10 clusters) was 15.4%. Diagnostic accuracy in specimens with ≥10 clusters was significantly higher (90.5% vs 36.4%) than that in specimens with fewer than10 clusters. Moreover, the unsatisfactory rate in patients aged ≥60 years was significantly higher (33.8% vs 13.2%) than that in patients younger than 60 years. Although the unsatisfactory rate was decreased, significant differences were not found between cases with fewer than five clusters (22.6%) and fewer than 10 clusters (33.8%) in patients aged ≥60 years. Diagnostic accuracy in cases with five or more clusters was significantly higher (90.3% vs 0%) than that in cases with fewer than five clusters. CONCLUSIONS: We propose that ≥10 clusters with ≥30 endometrial cells per cluster could be used as a specimen adequacy criterion for endometrial LBC. If ≥10 clusters cannot be found in patients aged ≥60 years, then the use of the alternative criterion of five or more clusters may yield satisfactory specimen adequacy.

Liquid-based endometrial cytology using SurePath™ is not inferior to suction endometrial tissue biopsy for detecting endometrial malignancies: Midterm report of a multicentre study advocated by Japan Association of Obstetricians and Gynecologists.

OBJECTIVE: We conducted a prospective, multicentre study to compare the clinical performance of liquid-based endometrial cytology (LBEC) using SurePath™ with that of suction endometrial tissue biopsy (SETB). This study is officially advocated and reported by the Japan Association of Obstetricians and Gynecologists. By publishing our midterm data, we intend to disseminate the benefits of LBEC system, using the descriptive reporting format and algorithmic interpretational approach. METHODS: From April 2014 to December 2015, we consecutively assessed 1116 LBEC specimens and 1044 SETB specimens in our five outpatient clinics. RESULTS: The sensitivity of suction tissue biopsies was 85.2%, whereas the sensitivity of LBEC was 92.2%. The specificity of suction tissue biopsies was 98.9% and that of LBEC was 98.5%. The negative predictive value of LBEC (99.1%) was higher than that of SETB (98.1%), although the difference between these values was not significant. CONCLUSIONS: The clinical performance of LBEC for detecting endometrial malignancies was almost identical to the performance of SETB. This indicates that LBEC was not inferior to SETB for the detection of endometrial cancer. The LBEC is appropriate for various clinical situations as the first-step detecting tool. In addition, it could be used for cancer surveillance for women with signs highly suggestive of endometrial malignancies and in Lynch syndrome patients, on a larger scale.

Current Ventilator and Oxygen Management during General Anesthesia: A Multicenter, Cross-sectional Observational Study.

BACKGROUND: Intraoperative oxygen management is poorly understood. It was hypothesized that potentially preventable hyperoxemia and substantial oxygen exposure would be common during general anesthesia. METHODS: A multicenter, cross-sectional study was conducted to describe current ventilator management, particularly oxygen management, during general anesthesia in Japan. All adult patients (16 yr old or older) who received general anesthesia over 5 consecutive days in 2015 at 43 participating hospitals were identified. Ventilator settings and vital signs were collected 1 h after the induction of general anesthesia. We determined the prevalence of potentially preventable hyperoxemia (oxygen saturation measured by pulse oximetry of more than 98%, despite fractional inspired oxygen tension of more than 0.21) and the risk factors for potentially substantial oxygen exposure (fractional inspired oxygen tension of more than 0.5, despite oxygen saturation measured by pulse oximetry of more than 92%). RESULTS: A total of 1,786 patients were found eligible, and 1,498 completed the study. Fractional inspired oxygen tension was between 0.31 and 0.6 in 1,385 patients (92%), whereas it was less than or equal to 0.3 in very few patients (1%). Most patients (83%) were exposed to potentially preventable hyperoxemia, and 32% had potentially substantial oxygen exposure. In multivariable analysis, old age, emergency surgery, and one-lung ventilation were independently associated with increased potentially substantial oxygen exposure, whereas use of volume control ventilation and high positive end-expiratory pressure levels were associated with decreased potentially substantial oxygen exposure. One-lung ventilation was particularly a strong risk factor for potentially substantial oxygen exposure (adjusted odds ratio, 13.35; 95% CI, 7.24 to 24.60). CONCLUSIONS: Potentially preventable hyperoxemia and substantial oxygen exposure are common during general anesthesia, especially during one-lung ventilation. Future research should explore the safety and feasibility of a more conservative approach for intraoperative oxygen therapy.

Human leukocyte antigen class II DRB1*1302 allele protects against cervical cancer: At which step of multistage carcinogenesis?

We investigated the role of human leukocyte antigen (HLA) class II alleles in multistage cervical carcinogenesis. Cross-sectional analysis for HLA association with cervical cancer included 1253 Japanese women: normal cytology (NL, n = 341), cervical intraepithelial neoplasia grade 1 (CIN1, n = 505), CIN grade 2 or 3 (CIN2/3, n = 96), or invasive cervical cancer (ICC, n = 311). The HLA class II allele frequencies were compared by Fisher's exact test or the χ(2) -test. The Bonferroni adjustment corrected for multiple comparisons. Among the study subjects, 454 women with low-grade squamous intraepithelial lesion cytology were prospectively monitored by cytology and colposcopy every 3-4 months to analyze cumulative risk of CIN3 within the next 10 years in relation to HLA class II alleles. HLA class II DRB1*1302 allele frequency was similar between women with NL (11.7%) and CIN1 (11.9%), but significantly decreased to 5.2% for CIN2/3 and 5.8% for ICC (P = 0.0003). Correction for multiple testing did not change this finding. In women with low-grade squamous intraepithelial lesion cytology, the cumulative risk of CIN3 diagnosed within 10 years was significantly reduced among DRB1*1302-positive women (3.2% vs. 23.7%, P = 0.03). In conclusion, the two different types of analysis in this single study showed the protective effect of the DRB1*1302 allele against progression from CIN1 to CIN2/3.

Evaluation of endometrial cytology prepared with the Becton Dickinson SurePath™ method: a pilot study by the Osaki Study Group.

OBJECTIVE: To evaluate the sensitivity and specificity of the BD SurePath™ liquid-based Papanicolaou test for assessing the cytology of intrauterine endometrial samples according to newly devised cytological diagnostic criteria and a novel descriptive reporting format. MATERIALS AND METHODS: One hundred and twenty-two endometrial samples were analyzed. All samples were obtained directly from the intrauterine cavity using the Uterobrush or Honest Super Brush. The samples used for the histological examination and cytological tests were collected simultaneously. Our study group devised new cytological diagnostic criteria for examining endometrial samples: the Osaki Study Group method. In this study, histological diagnosis was considered to be the gold standard for cytological diagnosis. A novel descriptive reporting format was also used. RESULTS: Satisfactory cytological specimens were obtained in all cases. The sensitivity and specificity of the SurePath endometrial cytological examination method were 96.4 and 100%, respectively. CONCLUSION: These results indicate that the SurePath method is acceptable for clinical use. Since the SurePath method seems to be easier and allows greater preparation standardization than the conventional method, coupling it with our newly devised cytological diagnostic criteria and descriptive reporting format might represent a reliable diagnostic method for assessing endometrial specimens.

Association between carotenoids and outcome of cervical intraepithelial neoplasia: a prospective cohort study.

BACKGROUND: It has been suggested that micronutrients such as alpha-tocopherol, retinol, lutein, cryptoxanthin, lycopene, and alpha- and beta-carotene may help in the prevention of cervical cancer. Our aim was to investigate whether serum concentrations and/or dietary intake of micronutrients influence the regression or progression of low-grade cervical abnormalities. METHODS: In a prospective cohort study of 391 patients with cervical intraepithelial neoplasia (CIN) grade 1-2 lesions, we measured serum micronutrient concentrations in addition to a self-administered questionnaire about dietary intake. We evaluated the hazard ratio (HR) adjusted for CIN grade, human papillomavirus genotype, total energy intake and smoking status. RESULTS: In non-smoking regression subjects, regression was significantly associated with serum levels of zeaxanthin/lutein (HR 1.25, 0.78-2.01, p = 0.024). This benefit was abolished in current smokers. Regression was inhibited by high serum levels of alpha-tocopherol in smokers (p = 0.042). In progression subjects, a significant protective effect against progression to CIN3 was observed in individuals with a medium level of serum beta-carotene [HR 0.28, 95 % confidence interval (CI) 0.11-0.71, p = 0.007), although any protective effect from a higher level of serum beta-carotene was weaker or abolished (HR 0.52, 95 % CI 0.24-1.13, p = 0.098). Increasing beta-carotene intake did not show a protective effect (HR 2.30, 95 % CI 0.97-5.42, p = 0.058). CONCLUSIONS: Measurements of serum levels of carotenoids suggest that regression is modulated by smoking status. Maintaining a medium serum level of beta-carotene has a protective effect for progression; however, carotene intake is not correlated with serum levels of carotenoids.

Do neutralizing antibody responses generated by human papillomavirus infections favor a better outcome of low-grade cervical lesions?

To determine the role of neutralizing antibody generated by human papillomavirus (HPV) infections, baseline levels of serum neutralizing antibodies directed against HPV 16 and cervical HPV DNA were determined in 242 unvaccinated women with low-grade cervical abnormalities, who were then monitored by cytology and colposcopy every 4 months. In women infected with HPV 16 (n = 42), abnormal cytology persisted longer in those positive for HPV 16-specific neutralizing antibodies at baseline (median time to cytological regression: 23.8 vs. 7.2 months). Progression to cervical precancer (cervical intraepithelial neoplasia grade 3) within 5 years occurred only among women carrying HPV 16-specific neutralizing antibodies (P = 0.03, log-rank test). In women infected with types other than HPV 16 (n = 200), detection of HPV 16-specific neutralizing antibodies was not correlated with disease outcome. In conclusion, development of specific neutralizing antibodies following natural HPV 16 infection did not favor a better outcome of low-grade cervical lesions induced by HPV 16 or by other types; rather, detection of neutralizing antibodies generated by current infection may reflect viral persistence and thus help identify those who are at high risk of disease progression.

HLA class II DRB1*1302 allele protects against progression to cervical intraepithelial neoplasia grade 3: a multicenter prospective cohort study.

OBJECTIVE: Genetic variations in human leukocyte antigens (HLA) class II regions may influence the risk of cervical cancer by altering the efficiency of the immune responses to human papillomavirus antigens. This prospective study was designed to evaluate the effects of HLA class II alleles on the natural course of cervical precursor lesions. METHODS: We followed a total of 454 Japanese women with cytological low-grade squamous intraepithelial lesion (LSIL) and histological cervical intraepithelial neoplasia grades 1 to 2 (CIN1-CIN2). Patients were tested for HLA class II alleles and cervical human papillomavirus DNA at the time of entry and then monitored by cytology and colposcopy every 4 months for a mean follow-up of 39.0 months. We analyzed cumulative probabilities of cytological regression to at least 2 consecutive negative Papanicolaou tests and histological progression to biopsy-positive CIN3. RESULTS: During the follow-up period, 39 lesions progressed to CIN3, and 282 lesions regressed to normal cytology. Progression to CIN3 did not occur in DRB1*1302-positive women, and this protective effect of DRB1*1302 was statistically significant (P = 0.03). Low-grade squamous intraepithelial lesion regressed to normal cytology more quickly in DRB1*1302-positive women than in DRB1*1302-negative women (median time, 8.9 months vs 14.2 months), although the difference was not statistically significant (P = 0.16). The risk of LSIL persistence or progression to CIN3 within 5 years was not affected by any other HLA class II alleles. CONCLUSION: By using a prospective study design, we demonstrated the protective effect of the DRB1*1302 allele against progression to CIN3 among Japanese women with LSIL.

Subsequent risks for cervical precancer and cancer in women with low-grade squamous intraepithelial lesions unconfirmed by colposcopy-directed biopsy: results from a multicenter, prospective, cohort study.

OBJECTIVE: To investigate the natural course of low-grade squamous intraepithelial lesions (LSILs) that cannot be histologically confirmed by colposcopy-directed biopsy. METHODS: In a multicenter, prospective, cohort study of Japanese women with LSILs, we analyzed the follow-up data from 64 women who had a negative biopsy result at the initial colposcopy (biopsy-negative LSIL) in comparison with those from 479 women who had a histologic diagnosis of cervical intraepithelial neoplasia grade 1 (LSIL/CIN1). Patients were monitored by cytology and colposcopy every 4 months for a mean follow-up period of 39.0 months, with cytologic regression defined as two consecutive negative smears and normal colposcopy. RESULTS: In women with biopsy-negative LSILs, there were no cases of CIN3 or worse (CIN3+) diagnosed within 2 years; the difference in the 2-year risk of CIN3+ between the two groups was marginally significant (0 vs. 5.5%; P = 0.07). The cumulative probability of cytologic regression within 12 months was much higher in the biopsy-negative LSIL group (71.2 vs. 48.6%; P = 0.0001). The percentage of women positive for high-risk human papillomaviruses (hrHPVs) was significantly lower in the biopsy-negative LSIL group than in the LSIL/CIN1 group (62.1 vs. 78.4%; P = 0.01); however, the 12-month regression rate of biopsy-negative LSIL was similar between hrHPV-positive and -negative women (67.3 vs. 74.4%, P = 0.73). CONCLUSION: In women with biopsy-negative LSILs, the risk of CIN3+ diagnosed within 2 years was low; furthermore, approximately 70% underwent cytologic regression within 12 months, regardless of HPV testing results. Biopsy-negative LSILs may represent regressing lesions rather than lesions missed by colposcopy.

Guidelines for office gynecology in Japan: Japan Society of Obstetrics and Gynecology and Japan Association of Obstetricians and Gynecologists 2011 edition.

Gynecology in the office setting is developing worldwide. Clinical guidelines for office gynecology were first published by the Japan Society of Obstetrics and Gynecology and the Japan Association of Obstetricians and Gynecologists in 2011. These guidelines include a total of 72 clinical questions covering four areas (Infectious disease, Malignancies and benign tumors, Endocrinology and infertility, and Healthcare for women). These clinical questions were followed by several answers, backgrounds, explanations and references covering common problems and questions encountered in office gynecology. Each answer with a recommendation level of A, B or C has been prepared based principally on evidence or consensus among Japanese gynecologists.These guidelines would promote a better understanding of the current standard care practices for gynecologic outpatients in Japan.

New terminology for intrauterine endometrial samples: a group study by the Japanese Society of Clinical Cytology.

OBJECTIVE: To evaluate the sensitivity and specificity of endometrial cytology obtained by intrauterine sample using a descriptive reporting format for endometrial cytological diagnosis. STUDY DESIGN: 10,152 consecutive endometrial scrapings obtained in 13 different Japanese hospitals were analyzed. Cytological results were classified as 'negative for malignancy', 'atypical endometrial cells' (ATEC), 'endometrial hyperplasia', 'atypical endometrial hyperplasia' or 'malignant tumor'. ATEC was subclassified as 'ATEC, of undetermined significance' (ATEC-US) and 'ATEC, cannot exclude atypical endometrial hyperplasia or more' (ATEC-A). Cytological results were compared with the histological diagnosis as a gold standard. When the cytological result was 'negative for malignancy' and there was no subsequent histological examination, the case was considered a true negative when the endometrium was assessed as normal on transvaginal ultrasonography and there was no abnormal uterine bleeding. RESULTS: 1,083 cases in which histology was not performed, 557 cases of 'unsatisfactory specimen' and 76 cases of ATEC-US were excluded. In the remaining 8,436 cases, the sensitivity and specificity, positive predictive value and negative predictive value for detecting atypical endometrial hyperplasia or malignant tumors were 79.0 and 99.7, 92.9 and 98.9%, respectively. CONCLUSION: The current diagnostic standards for endometrial cytology in Japan were established. Specificity is satisfactory for excluding cancer or precancerous diseases.

Predicting the progression of cervical precursor lesions by human papillomavirus genotyping: a prospective cohort study.

Only a subset of cervical precursor lesions progress to cervical cancer and because of the lack of the predictive markers, it cannot be ascertained which lesions will progress or not. To estimate the risk of disease progression associated with human papillomavirus (HPV) genotypes, we followed 570 Japanese women with cytological LSIL (low-grade squamous intraepithelial lesion) and histological CIN (cervical intraepithelial neoplasia) grade 1-2 lesions (479 CIN 1; 91 CIN 2) at 3 to 4 month intervals for a mean follow-up period of 39.1 months. At entry, we detected HPV DNA in cervical samples by polymerase chain reaction-based methodology. Over the period of follow-up period, 46 lesions progressed to CIN 3 while 362 regressed to normal cytology. Women with multiple HPV infections were more likely to have persistent lesions (hazard ratio [HR] for regression, 0.65; 95% confidence interval [CI], 0.42-1.02; p = 0.07); however, multiple infections did not increase the risk of progression (HR for progression, 1.04; 95% CI, 0.37-2.94; p = 0.94). After adjusting for CIN grade and women's age, HRs for progression to CIN 3 (vs. women with low-risk types or negative for HPV DNA) varied markedly by HPV genotype: type 16 (11.1, 95% CI: 1.39-88.3); 18 (14.1, 0.65-306); 31 (24.7, 2.51-243); 33 (20.3, 1.78-231); 35 (13.7, 0.75-251); 52 (11.6, 1.45-93.3); 58 (8.85, 1.01-77.6); other high-risk types (4.04, 0.47-34.7). HPV 45 was not detected in our study subjects. The cumulative probability of CIN 3 within 5 years was 20.5% for HPV 16, 18, 31, 33, 35, 52 and 58; 6.0% for other high-risk types; 1.7% for low-risk types (p = 0.0001). In conclusion, type-specific HPV testing for women with LSIL/CIN 1-2 lesions is useful for identifying populations at increased or decreased risk of disease progression.

Stage IA ovarian cancers: comparison of sonographic findings and histopathologic types between patients with normal and elevated serum cancer antigen 125 levels.

OBJECTIVES: The purpose of this study was to compare sonographic findings and histopathologic types of stage IA ovarian cancers between groups with normal and elevated cancer antigen 125 (CA-125) levels. METHODS: Between 2000 and 2009, 146 stage IA ovarian cancers were treated surgically (85 invasive and 61 borderline, 73 self-referred with tumor-related symptoms, 20 self-referred with nonspecific symptoms, 52 identified through screening, and 1 other). Of these, 87 cases (60%) had normal serum CA-125 levels (<35 U/mL). Their pre-operative sonographic findings and histopathologic types were compared to those of cases with elevated CA-125 levels. RESULTS: Statistically significant differences were found between the proportions of patients with elevated CA-125 levels in groups having tumors with maximal diameters of less than 20 cm and at least 20 cm (P = .03) and groups having tumors with less than 50% and 50% to 80% solid components (P = .02). In the group with normal CA-125 levels, we found predominantly mucinous adenocarcinoma in multilocular cysts with less than 50% solid components (25 cases), and clear cell adenocarcinoma in unilocular cysts with less than 50% solid components (12 cases), whereas in the group with elevated CA-125 levels, mucinous adenocarcinoma in multilocular cysts with less than 50% solid components (19 cases) and endometrioid adenocarcinoma in solid tumors (≥80% solid components) were predominant (5 cases). CONCLUSIONS: Stage IA ovarian cancers with normal CA-125 levels tend to be smaller, have less solid components, and have a slightly different distribution of histopathologic types than cancers with elevated CA-125 levels.

Tobacco smoking and regression of low-grade cervical abnormalities.

The role of tobacco smoking in the multistage carcinogenesis at the cervix is not fully understood because of a paucity of prospective data. To assess the relationship between smoking and spontaneous regression of cervical precursor lesions, a total of 516 women with low-grade squamous intraepithelial lesion (LSIL) were monitored by cytology and colposcopy every 4 months. Probability of LSIL regression within 2 years was analyzed in relation to smoking behaviors, with regression defined as at least two consecutive negative Pap smears and normal colposcopy. Women's age, initial biopsy results, and human papillomavirus (HPV) genotypes were included in the multivariate models for adjustments. Our study subjects included 258 never-smokers and 258 smokers (179 current and 79 former smokers). During a mean follow-up time of 39.8 months, 320 lesions regressed to normal cytology. Probability of regression within 2 years was significantly lower in smokers than in never-smokers (55.0%vs 68.8%, P = 0.004). The risk of LSIL persistence increased with smoking intensity and duration and with younger age at starting smoking (P = 0.003, P < 0.001, and P = 0.03, respectively). Smokers had twice as high a risk of persistent HPV infection compared to never-smokers (odds ratio, 2.50; 95% confidence interval, 1.30-4.81; P = 0.006). In young women, passive smoking since childhood reduced probability of regression within 2 years (56.7%vs 85.9%, P < 0.001). Further adjustments for a wide range of cervical cancer risk factors did not change the findings. In conclusion, tobacco smoking may interfere with regression of cervical precursor lesions. Childhood exposure to second-hand smoke may increase a risk of persistent cervical abnormalities among young women.

Evidence-based guidelines for treatment of cervical cancer in Japan: Japan Society of Gynecologic Oncology (JSGO) 2007 edition.

Clinical practice guidelines for gynecologic cancers have been published by the National Comprehensive Cancer Network and the National Cancer Institute. Whereas these guidelines form the basis for the standard of care for gynecologic malignancies in the United States, it has proven difficult to institute them in Japan due to differences in patient characteristics, health-care delivery systems, and insurance programs. Therefore, evidence-based guidelines for treating cervical cancer specifically in Japan have been under development. The Guidelines Formulation Committee and Evaluation Committee were independently established within the Committee for Treatment Guidelines for Cervical Cancer. Opinions from within and outside the Japan Society of Gynecologic Oncology (JSGO) were incorporated into the final draft, and the guidelines were published after approval by the JSGO. These guidelines are composed of ten chapters and comprise three algorithms. Each chapter consists of a clinical question, recommendations, background, objectives, explanations, and references. The objective of these guidelines is to clearly delineate the standard of care for cervical cancer treatment in Japan in order to ensure equitable care for all Japanese women diagnosed with cervical cancer.

A Diagnostic Approach to Endometrial Cytology by Means of Liquid-Based Preparations.

The adoption of endometrial cytology as a diagnostic procedure has been hampered in the past by difficulties arising in interpreting the cellular findings due to a number of factors (such as excess blood, cellular overlapping, and the complex physiology of endometrium). Recently, the use of liquid-based cytology (LBC), with its ability to remove blood and mucus and to distribute cells uniformly in a thin layer on the slide, has provided an opportunity to reevaluate the role of endometrial cytology. LBC samples are easier to screen compared to conventional ones, due to a smaller screening area and an excellent quality of cell preparations. LBC by using peculiar cytoarchitectural features is a useful tool in the cellular diagnosis and follow-up of abnormalities, which, however, remains complementary to histopathology and to the emerging molecular diagnostic cytopathology. This review discusses these various entities and takes into consideration the ancillary techniques that may be useful in the diagnostic procedure. Herein, we also summarize the process and rationale by which updates were made to the standardized terminology in 2018 and outline the contents of the new Bethesda-style classification (the Yokohama system) for the endometrial cytology.

Cross-sectional analysis of germline BRCA1 and BRCA2 mutations in Japanese patients suspected to have hereditary breast/ovarian cancer.

The prevalence of BRCA1/2 germline mutations in Japanese patients suspected to have hereditary breast/ovarian cancer was examined by a multi-institutional study, aiming at the clinical application of total sequencing analysis and validation of assay sensitivity in Japanese people using a cross-sectional approach based on genetic factors estimated from personal and family histories. One hundred and thirty-five subjects were referred to the genetic counseling clinics and enrolled in the study. Full sequencing analysis of the BRCA1/2 gene showed 28 types of deleterious mutations in 36 subjects (26.7%), including 13 types of BRCA1 mutations in 17 subjects (12.6%) and 15 types of BRCA2 mutations in 19 subjects (14.1%). Subjects were classified into five groups and 22 subgroups according to their personal and family history of breast and/or ovarian cancer, and the prevalence of deleterious mutations was compared with previously reported data in non-Ashkenazi individuals. Statistical analysis using the Mantel-Haenszel test for groups I through IV revealed that the prevalence of Japanese subjects was significantly higher than that of non-Ashkenazi individuals (P = 0.005, odds ratio 1.87, 95% confidence interval 1.22-2.88). Family history of the probands suffering from breast cancer indicated risk factors for the presence of deleterious mutations of BRCA1/2 as follows: (1) families with breast cancer before age 40 within second degree relatives (P = 0.0265, odds ratio 2.833, 95% confidence interval 1.165-7.136) and (2) families with bilateral breast cancer and/or ovarian cancer within second degree relatives (P = 0.0151, odds ratio 2.88, 95% confidence interval 1.25-6.64).