Barriers to undergoing cervical cancer screening among health sciences university students in Japan: A cross-sectional study.

In most developed countries, cervical cancer screening and human papillomavirus vaccination have reduced cervical cancer incidence. However, the incidence has been increasing in Japan, possibly because of the low screening rate. Although cervical cancer incidence has increased in people in their 20s, the screening rate among 20-24-year-olds in Japan is only 10.2%, meaning that cervical cancer screening rates should be increased among young Japanese women. We conducted a questionnaire survey among students at health sciences universities to determine their knowledge of cervical cancer, screening rates, and barriers to screening. Students taking specialized medical courses were highly knowledgeable; recognition of the facts that "cervical cancer can be prevented through screening" and that "the risk of cervical cancer increases in one's 20s" was significantly high among those who underwent screening. On the other hand, only 7.5% of students used the free coupons provided for screening. Knowledge of cervical cancer improves screening rates. Therefore, educational programs to raise awareness of the importance of cervical cancer screening among non-medical and health sciences university students and young women in general are required.

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.

Assessment of the localization of chondroitin sulfate in various types of endometrial carcinoma.

INTRODUCTION: This study aimed to assess the localization of chondroitin sulfate (CS), a primary extracellular matrix component, in the stromal region of endometrial carcinoma (EC). METHODS: Immunostaining was performed on 26 endometrial endometrioid carcinoma (EEC) samples of different grades and 10 endometrial serous carcinoma (ESC) samples to evaluate CS localization. This was further confirmed by Alcian Blue (AB) staining as well. RESULTS: In the G1-EEC samples, CS showed reactivity with fibrovascular stroma, supporting closely packed glandular crowding and papillary structures. As the grade increased, the original interstitial structure was re-established, and the localization of CS in the perigulandular region decreased. In the ESC samples, the thick fibrous strands supporting the papillary architecture showed reactivity with CS; however, the delicate stromal region branching into the narrow region showed poor reactivity. The AB staining results showed similar characteristics to the immunostaining ones. CONCLUSIONS: The characteristic localization of CS in various EC types was elucidated. The present study provides new information on endometrial stromal assessment.

Can Mitotic Figures in Hyperchromatic Crowded Groups be Cytodiagnostic Criteria for High-Grade Squamous Intra-epithelial Lesions?

Aims: The present study aimed to investigate whether the presence of mitoses in hyperchromatic crowded groups (HCGs) in cervical cytological specimens can serve as cytological criteria for high-grade squamous intra-epithelial lesions (HSILs). Methods and Material: Various parameters were examined, including the frequency of mitotic figures per high power field (HPF) in Pap, hematoxylin eosin (HE) samples, and PHH3 immunocytochemical (ICC) and immunohistochemical (IHC) analyses. Results: In the Pap and PHH3-ICC samples, the number of mitotic figures observed in HCGs was significantly higher in HSIL (P < 0.001) compared to other groups. Furthermore, the frequency of observing two or more mitoses was significantly higher in HSIL (Pap: P = 0.002, PHH3-ICC: P < 0.001) than in low-grade squamous intra-epithelial lesions (LSILs). Moreover, a comparison between Pap samples and PHH3-ICC showed that the frequency of two or more mitoses was significantly higher in the PHH3-ICC analysis of HSIL (P = 0.042). Regarding HE and PHH3-IHC samples, counting the number of mitoses in the lower and middle/upper layers of the squamous epithelial layer revealed that HSIL had a significantly higher value (HE: P = 0.0089, PHH3-IHC: P = 0.0002) than LSIL in the middle/upper layers. Conclusions: Hence, the presence of two or more mitotic figures in HCGs per HPF in cervical cytology indicates a suspicion of HSIL. The detection of mitoses in PHH3-ICC samples is more sensitive and easier to observe than in Pap samples, making it a valuable mitotic marker.

Efficacy of the Antigenicity-Retaining Ability of Fixative Solutions for Liquid-Based Cytology: Immunocytochemistry of Long-Term Storage.

INTRODUCTION/OBJECTIVE: Liquid-based cytology (LBC) is advantageous as multiple stained specimens can be prepared and used for additional assays such as immunocytochemical and molecular-pathological investigations. Two types of preservative-fixative solutions (fixatives) are used for nongynecologic specimens used in the BD SurePath-LBC (SP-LBC) method, and their components vary. However, few studies have evaluated the differences in antigen-retaining ability between these fixatives. Therefore, we investigated and compared the antigen-retaining ability of the fixatives in immunocytochemical staining (ICC) under long-term storage conditions. MATERIALS AND METHODS: Sediments of cultured RAJI cells (derived from Burkitt's lymphoma) were added to each fixative (red and blue) and stored at room temperature for a specified period (1 h; 1 week; and 1, 3, and 6 months). The specimens were then prepared using the SP-LBC method and subjected to ICC. Positivity rate was calculated using the specimens fixed at room temperature for 1 h as a control. Antibodies against Ki67 expressed in the nucleus and against CD20 and leukocyte common antigen (LCA) expressed on the cell membrane were used. RESULTS: For CD20 and LCA, the positivity rate increased with time in the red fixative compared with that in the control. In the blue fixative, the positivity rate was highest at 1 h and was maintained at a high level throughout the storage period. In contrast, the Ki67 positivity rate was highest at 1 h in both red and blue fixatives and markedly decreased with time. Therefore, although refrigerated (8°C) storage was used, no improvement was noted. CONCLUSIONS: Long-term storage is possible for cell membrane antigens at room temperature; however, it is unsuitable for intranuclear antigens. Therefore, we conclude that suitable fixative type and storage temperature differ based on antigen location. Further investigation is warranted.

A Method for Deriving Quasi-healthy Cohorts From Clinical Data.

We evaluated quasi-healthy cohorts (model cohorts), derived from clinical data, to determine how well they simulated control cohorts. Control cohorts comprised individuals extracted from a public checkup database in Japan, under the condition that their values for 3 basic laboratory tests fall within specific reference ranges (3Ts condition). Model cohorts comprised outpatients, extracted from a clinical database at a hospital, under the 3Ts condition or under the condition that their values for 4 laboratory tests fall within specific reference ranges (4Ts condition). Because even a patient with a serious illness, such as cancer, may present with normal values on basic laboratory tests, one additional condition was added: the duration (1 or 3 months; 1M or 3M) during which patients were not hospitalized after their first laboratory test. For evaluations, cohorts were specified by age and sex. The 4Ts + 3M condition was the most effective condition, under which model cohorts were used to successfully simulate age-dependent changes and sex differences in laboratory test values for control cohorts. Therefore, by properly setting the conditions for extracting quasi-healthy individuals, we can derive cohorts from clinical data to simulate various types of cohorts. Although some issues with the proposed method remain to be solved, this approach presents new possibilities for using clinical data for cohort studies.

Evaluation of the Anonymity and Utility of De-Identified Clinical Data Based on Japanese Anonymization Criteria.

We analyze the deterioration of clinical data quality due to anonymization. The result shows that data quality remained high with micro-aggregation and also verify the availability of noise addition to prevent illegal re-identification by matching another personal data.

Comparison of two liquid preservatives for SurePath™ slides prepared from voided urine.

Blood-rich gynecologic specimens can be problematic in the processing of liquid-based cytology. However, little is known about the influence of erythrocytes and protein on urine specimens. In addition, the SurePath™ system has two preservatives for non-gynecologic specimens. In this study, we compared the epithelial cell counts and cytomorphology obtained from CytoRich™ (CR) Red and CR Blue. A total of 98 voided urine samples were processed using both CR Red and CR Blue. We made an assessment of the epithelial cell counts, fixation, and staining quality, and backgrounds of both slides. Urine protein and urine erythrocyte counts were analyzed, and those data were compared with the epithelial cell counts in CR Red and CR Blue slides. Overall, epithelial cell counts were equivalent for both CR Red and CR Blue slides. However, in high-level proteinuria cases, the CR Red slides showed higher epithelial cell counts than the CR Blue slides. On the other hand, in microscopic hematuria cases, the CR Blue slides showed higher epithelial cell counts than the CR Red slides. We have found both CR Red and CR Blue to be available for urine cytology. However, it is important to note that CR Blue is inferior to CR Red in epithelial cell recovery rates in cases of high-level proteinuria.