Development and validation of a predictive model for endocervical curettage in patients referred for colposcopy:A multicenter retrospective diagnostic study in China

Objective:This study aimed to develop a nomogram that can predict occult high-grade squamous intraepithelial lesions or worse(HSIL+)and determine the need for endocervical curettage(ECC)in patients referred for colposcopy.Methods:This retrospective multicenter study included 4,149 patients who were referred to any one of six tertiary hospitals in China for colposcopy between January 2020 and November 2021 because of abnormal screening results.ECC data were extracted from the medical records.Univariate and multivariate logistic regression analyses were performed to identify factors that could predict HSIL+on ECC.Patients were randomly assigned to a training set or to an internal validation set for performance and comparability testing.The model was externally validated and tested in patients from two additional hospitals.The nomogram was assessed in terms of discrimination and calibration and subjected to decision curve analysis.Results:HSIL+was found on ECC in 38.8%(n=388)of cases.Our predictive nomogram included age group,cytology,human papillomavirus(HPV)status,visibility of the cervix and colposcopic impression.The nomogram had good overall discrimination,which was internally validated[area under the receiver-operator characteristic(AUC),0.839;95%confidence interval(95%CI),0.773-0.904].In terms of external validation,the AUC was 0.843(95%CI,0.773-0.912)for the consecutive sample and 0.843(95%CI,0.783-0.902)for the comparative sample.Calibration analysis suggested good consistency between predicted and observed probabilities.Decision curve analysis suggested this nomogram would be clinically useful with almost the entire range of threshold probabilities.Conclusions:This internally and externally validated nomogram can be easily applied and incorporates multiple clinically relevant variables that can be used to identify patients with occult HSIL+who need ECC.

Endocervical Swab Microbial Isolates among Women with Third Degree Uterovaginal Prolapse

Background: Uterovaginal prolapse is the descent of the uterus through the vaginal canal. This may be a predisposing factor to infections in the urogenital system. This study aimed to assess the endocervical swab microscopy, culture and sensitivity in patients with third degree uterovaginal prolapse at the National Obstetric Fistula Centre, Abakaliki, South-East Nigeria. Methodology: This is a cross-sectional prospective study to assess the endocervical swab microbial findings in patients with third degree uterovaginal prolapse using simple random sampling technique. Data on sociodemographic variables, risk factors for pelvic organ prolapse, and endocervical swab findings among women with third degree uterovaginal prolapse were collated and analysed using statistical methods. Results: The mean age and parity were 50.5 years ± 9.1 and 6.7 ± 2.0 respectively. Thirty-six (85.7%) of the clients were grandmultipara and 37 (88.1%) were farmers. Pus cells were present in all samples while 27 (64.3%) had microbial isolates. Streptococcus pyogenes was isolated in 7 (16.7%), Streptococcus faecalis in 5 (11.9%), Escherichia coli in 5 (11.9), Staphylococcus aureus in 4 (9.5%), Klebsiella pneumoniae in 2 (4.8%) and Yeast cells in 4 (9.5%) of the endocervical swabs. All isolates were sensitive to gentamicin. Bacterial isolates were resistant to amoxicillin/clavulanic acid. Conclusion: This study showed growth of pathogenic organisms from the endocervix of women with third degree uterovaginal prolapse. A 100% sensitivity to gentamicin was observed in the study.

Role of Toll-like receptor 4 and human defensin 5 in primary endocervical epithelial cells

Background Endocervical epithelial cells play early roles in the defense of upper female genital tract to pathogens. Toll-like receptors （TLRs） and human defensins （HD） have recently been identified as fundamental components of the innate immune responses to bacterial pathogens. We aimed to use in vitro model of human primary endocervical epithelial cells （HPECs） to investigate their roles in innate immune response of the endocervix. Methods TLR4 expression and distribution in HPECs and endocervix were investigated by immunofluorescence （IF）. Cultured HPECs were divided into lipopolysaccharide （LPS） group which were treated by LPS for 0, 24 and 48 hours, and control group without treatment. At each time point, the levels of HD5, IL-6 and TNF-a in supernants were determined by ELISA. TLR4 and HD5 expressions of cells were detected by Western blotting simultaneously. HD5 expression pattern was also compared between the HeLa cell line and HPECs. Results Endocervix tissue surface and HPECs expressed TLR4. After incubated with LPS, HPECs expressed significantly higher levels of TLR4 than control group, especially after 24 hours （P 〈0.01）, however decreased after 48 hours with a similar level of TLR4 expression compared with control group. LPS could upregulate the secretion of HD5, IL-6 and TNF-a in a time-dependent manner （24 hours： P 〈0.05; 48 hours： P 〈0.01, compared with control group）. Intracellular HD5 expression levels decreased over time. HD5 expression patterns in HPECs were different from HeLa cell line. Conclusions To respond to LPS stimulation, HPECs may function in the mucosal immune defense through TLR4 activation and HD5 secretion. HPEC is considered a significant model for immunological study.

The Importance of Endocervical Curettage in an Old Post-Loop Electrosurgical Excision Procedure Woman with Abnormal Cervical Cytology and a Normal Punch Biopsy Histology:A Case Report and Literature Review

Endocervical curettage(ECC)is an optional practice during colposcopy,and the indication for endocervical curettage(ECC)is controversial between Europe and the USA.Here,we explored the value of ECC in a specific situation.An elderly post-loop electrosurgical excision procedure woman,who had undergone a colposcopy 4 months before,went for her follow-up and abnormal cytology was found,and both the ECC and punch biopsy showed negative results.Then,a second ECC was performed,which led to the diagnosis of a high-grade squamous intraepithelial lesion.This case report shows that ECC is useful for diagnosing elderly women with Type 3 squamocolumnar junction.

Total Laparoscopic Hysterectomy for Diagnosis and Treatment of Cervical Cystic Lesions: A Case Series

Objective: Cervical cystic lesions are often observed in gynecological clinical practice. Many are caused by benign diseases such as lobular endocervical glandular hyperplasia (LEGH), and it is important to differentiate these lesions from those due to malignant diseases such as minimal deviation adenocarcinoma (MDA). In cases in which fertility preservation is not a concern, the final pathology is often confirmed by hysterectomy. To investigate the feasibility and safety of laparoscopic surgery for cervical cystic lesions, we retrospectively examined cases in which total laparoscopic hysterectomy (TLH) was performed for diagnosis and treatment. Methods: The subjects were 28 women who underwent TLH from April 2012 to March 2017 at Keio University Hospital. The pre- and post-operative courses of these patients were examined. Results: The average age was 49.4 (range 39 - 65) years and the mean body mass index was 21.7 (16.8 - 30.5) kg/m2. The average operation time was 159 (101 - 314) min and the average bleeding volume was 106.8 (0 - 600) g. There were no severe perioperative complications. The average hospital stay was 8.4 (7 - 14) days. In postoperative pathological diagnosis, 13 cases had benign diseases such as Nabot cysts, there were 14 cases of LEGH, and one patient was diagnosed with MDA. In the MDA case, additional bilateral salpingo-oophorectomy and pelvic lymph node dissection were performed at a later date. No metastasis was observed in these excised specimens. Conclusions: Our results suggest that TLH for cervical cystic lesions can be performed safely. However, it is important to consider the TLH indication before surgery based on the possibility of malignant disease.

Semen lactoferrin promotes CCL20 production by epithelial cells: Involvement in HIV transmission

AIM: To study the effect of seminal plasma on Chemokine(C-C motif) ligand 20(CCL20) production by epithelial cells and its relationship with lactoferrin.METHODS: HEC-1A cells, a cell line derived from a monostratified endocervical epithelium, were incubated with samples of seminal plasma(diluted 1:10 in culture medium) recovered from human immunodeficiency virus(HIV) seronegative(HIV-) or HIV seropositive(HIV+) subjects. Recombinant human interleukin 1 beta(IL-1β) was used as positive control, and culture medium only as negative control. The measurement of CCL20 production in the supernatants of HEC-1A cells and of lactoferrin in seminal plasma was determined by enzyme-linked immunosorbent assay techniques. A fractionation of seminal plasma proteins was performed by ion exchange chromatography on a pool of seminal plasma specimens from HIV- subjects. Each fraction was tested for its ability to stimulate the production of CCL20 by HEC-1A cells and for its lactoferrin concentration. The HIV viral load in seminal plasma samples from HIV+ patients was measured using the HIV-Monitor kit(Roche Diagnostic Systems, Branchburg, NJ, United States).RESULTS: The positive control IL-1β was responsible for an increase of 11.36 ± 3.36 times in the production of CCL20. Stimulation of HEC-1A cells was performed in 34 seminal plasma samples(22 from HIV+ subjects and 12 from HIV- subjects). The mean production of CCL20 by HEC-1A in presence of seminal plasma from HIV- and HIV+ subjects was respectively 5.38 ± 0.91 and 7.57 ± 3.26 times higher than that obtained with the untreated cells(P < 0.05 between the two groups). Using the same 34 specimens of seminal plasma, no correlation was observed between the concentration of total proteins in seminal plasma and their ability to stimulate the secretion of CCL20 by HEC-1 cells. In contrast, the ability to produce CCL20 by HEC-1A cells correlated to the concentration of lactoferrin in the seminal plasma samples(r coefficient = 0.56; CI: 0.26-0.76; P < 0.001). After fractionation by ion exchange chromatography, the seminal plasma fractions exhibiting the highest concentrations of lactoferrin were responsible for the greatest stimulation of CCL20 production by HEC-1A cells(r coefficient = 0.89; CI: 0.78-0.95; P <0.0001). CONCLUSION: Lactoferrin present in seminal plasma correlated with an increased production of CCL20 by HEC-1A cells and therefore could facilitate HIV entry through the genital mucosa.

A Study on Clinical Management of Glandular Changes in Cells on Cervical Cytology

A cytological cervical smear abnormality of glandular origin raises a high suspicion of underlying invasive or pre invasive cancers. Objective: To look into the diagnosis and management of women presenting with glandular changes on cervical cytology and to further implement a good management plan for these women. Methods: This study is a retrospective review of all patients referred to North Cumbria Integrated Care (NCIC) NHS foundation trust, United Kingdom with glandular changes on their cervical smear result between January 2015 and December 2020. Data was collected from the hospital colposcopy data base. Results: This study comprised of a sample size of 65 women. 11 of these (17%) were referred with borderline changes in their endocervical cells and 54 (83%) referred with a ?glandular neoplasia of endocervical type. There were colposcopically significant lesions (high grade lesions or suspected adenocarcinoma) for 52 (80%) of the women. All but one (98%) had Large loop excition of transformation zone (LLETZ) after colposcopy. Histologically, 8 (12%) women were diagnosed with adenocarcinoma, 29 (45%) were diagnosed with high grade cervical glandular intraepithelial neoplasia (HGCGIN), 9 (14%) had high grade cervical intraepithelial neoplasia (CIN2/3), 2 (3%) had low grade cervical glandular intraepithelial neoplasia (LGCGIN), 4 (6%) had a normal histology and 10 (15%) had lesions of mixed origin. After their first LLETZ treatment, 24 (37.5%) needed repeat LLETZ, 8 (12%) had a hysterectomy and one woman had radical trachelectomy.

Value of frozen section examination in diagnosis and treatment of high-grade cervical intraepithelial neoplasia

Background Invasive cancer of the cervix is considered a preventable disease because it has a long pre-invasive state, cervical cytology screening programs are currently available, and treatment of pre-invasive lesions is effective. We tested the accuracy of frozen section examination （FSE） of cone specimens to identify the endocervical margin and rule out invasion in patients with high-grade cervical intraepithelial neoplasia （CIN）. Methods For 320 consecutive patients with a preoperative biopsy result of CIN stage 2/3, cold-knife conization （CKC） was performed followed by FSE. The results from analyses of permanent paraffin sections （PS） were compared with the FSE findings. Results The accuracy of FSE was 87% （278/320）. For all of the seven patients with an invasive squamous cell carcinoma of the cervix identified by FSE, the diagnosis was confirmed by PS analysis. For one patient, the FSE result was cervicitis, whereas PS ananlysis showed microinvasive carcinoma. Appropriate surgery was performed for all patients based on the FSE and biopsy results. The FSE and PS results were not significantly different （P=-0.000）. Definitive examination of margin status using PS was concordant with FSE findings in all cases. Conclusions FSE is a rapid and reliable method for evaluating CKC specimens. It can identify frank invasion, permit adequate treatment in a one-stage procedure, and reliably detect clear resection margins. Since discrepancies do exist and may result in inappropriate treatment, further research is required to decrease these discrepancies and avoid missing even one case.