Efficacy of Lidocaine Spray for Pain Reduction during Colposcopy-Directed Cervical Biopsies: A Randomized Controlled Trial.

Objectives: The objective of this study was to evaluate the efficacy of lidocaine spray in reducing the pain during colposcopy-directed cervical biopsy (CDB). Methods: From December 2017 to February 2019, 312 women undergoing CDBs were enrolled. The participants were randomized to three groups: group 1 (lidocaine spray), in which lidocaine spray was applied thoroughly to the cervix; group 2 (placebo), in which normal saline was applied thoroughly to the cervix; and group 3 (control), in which no anesthetic agent was applied to the cervix. Each woman completed a 10 cm visual analog scale to classify the subjective pain experience at three time points: baseline, immediately after biopsy, and 10 min after the procedure. The primary outcome of this study was the biopsy pain score. Results: The 312 enrolled women were randomly assigned to the three groups, amounting to 104 women per group. The clinical and pathological characteristics of the participants in all groups were comparable. The baseline, the biopsy, and the post-procedure pain scores were comparable among the three groups. There was a significant increase in the pain score from baseline to biopsy and from baseline to post-procedure in each group. The pain-score changes from baseline to biopsy in the lidocaine spray group significantly decreased when compared with the normal saline group (<0.001), and tended to decrease, though not significantly (p = 0.06), when compared with the control group. No complication with the intervention was observed. Conclusions: The application of lidocaine spray to the cervix has the benefit of reducing the pain associated with CDBs by a small amount. However, the intervention is safe and may be considered in nulliparous and/or overly anxious women undergoing the procedure.

Clinical Performance of Self-collected Specimen HPV-DNA vs Clinician- collected Specimen HPV-mRNA to Detect High-risk HPV and High-grade Cervical Lesions and Cancer.

OBJECTIVE: Self- collected specimens to detect high-risk (hr) HPV and high-grade cervical lesions (CIN2+) has been introduced aiming to increase cervical cancer screening coverage. The performance of self- collected specimen  compared to clinician collected specimen is one major concern. This study aimed to compare self-sampling HPV-DNA and clinician-sampling HPV-mRNA to detect hr-HPV and high-grade cervical lesions. METHODS: Women with abnormal cervical cytology and/ or positive hr-HPV who attended the colposcopy clinics in 10 tertiary hospitals in Bangkok were enrolled. Self-collected specimens were evaluated for  HPV DNA using Cobas® 4800 HPV test prior to the clinician-collected specimens which were tested for HPV mRNA with APTIMA® HPV Assay. Subsequent colposcopy with biopsy was performed. The detection rates of hr-HPV from both HPV tests and their performance to detect high-grade lesions pathology were compared. RESULTS: Data from 497 women's specimens were analyzed. Both samplings had 86.8% concordance rate in detecting hr-HPV (Kappa 0.670; 95% confidence interval [CI] 0.599-0.746, P value < 0.001). The sensitivity (95% CI) of self-collected specimen HPV DNA and clinician- collected specimen HPV-mRNA to detect high-grade lesions were 91.8% (85.4%-96.0%) and 90.2% (83.6%-94.9%) respectively. The corresponding negative predictive values (95% CI) were 91.9% (85.6%-96.0%) and 91.7% (86.0%-95.7%) respectively. CONCLUSION: HPV DNA testing from self-collected specimen to detect HR-HPV demonstrates high concordance with HPV mRNA testing from clinician-collected specimen. The sensitivity and negative predictive value of both tests to detect high-grade lesions are comparable.

Self- and physician-collected high-risk human papillomavirus (HPV) testing to detect high-grade cervical lesions among Thai women.

OBJECTIVE: We compared the performance of high-risk human papillomavirus (HPV) messenger RNA testing of physician- and self-collected specimens for detecting histological grade 2 or higher cervical intraepithelial neoplasia (CIN) among women who visited a colposcopy clinic in Thailand. METHODS: From January 2022 to April 2022, 500 women participated in this cross-sectional multicenter study; 494 had complete data and valid specimen results. The participants were women who attended any one of the 10 participating institutes' colposcopy clinics due to abnormal cytology, positive high-risk HPV testing, or for follow-up. Participants used a self-sampling Aptima Multitest Swab specimen collection kit to self-collect vaginal samples before physicians biopsied the cervix during the colposcopic examination. The self- and physician-collected specimens were tested for high-risk HPV messenger RNA using Aptima nucleic acid amplification assays. Cervical tissues were collected during colposcopic-directed biopsy from the most severe lesion or a random biopsy and endocervical curettage specimen if no lesion was detected. RESULTS: We detected high-risk HPV messenger RNA in 75.4% of self-collected specimens and 70.6% of physician-collected specimens. The prevalence of histological grade 2 or higher CIN from cervical histology was 25.1% (n=124). For self-collected specimens, the sensitivity and specificity of high-risk HPV messenger RNA for grade 2 or higher CIN were 87.0% (95% CI 79.7% to 92.4%; n=108) and 28.5% (95% CI 24.0% to 33.4%). For physician-collected specimens, the sensitivity and specificity of high-risk HPV messenger RNA for grade 2 or higher CIN were 90.2% (95% CI 83.6% to 94.9%; n=112) and 36.1% (95% CI 31.2% to 41.3%). CONCLUSIONS: Self-collected specimens for high-risk HPV messenger RNA testing demonstrated good sensitivity and negative predictive value for detecting grade 2 or higher CIN in Thai women attending the participating institutes' colposcopy clinics. Self-collected samples performed similarly to physician-collected ones.

Effectiveness of enhanced recovery after surgery protocol in open gynecologic oncology surgery: A randomized controlled trial.

OBJECTIVE: To examine the effectiveness of applying the recommended enhanced recovery after surgery (ERAS) protocol compared with our usual care in women with gynecologic malignancy undergoing elective laparotomy. METHODS: From June 2020 to May 2021, 93 women with gynecologic cancers (cervix, endometrium, and ovary) undergoing elective laparotomy at our institution were randomly assigned into an intervention group (ERAS protocol, 46 women) or control group (usual care, 47 women). For the intervention group, each woman was brought through the pre-specified ERAS protocol starting from preoperative counseling to postoperative management. For the control group, participants underwent routine standard care. The primary outcomes were length of hospital stay and postoperative pain. RESULTS: The intervention group demonstrated shorter hospital stay by 20 h (47.48 h vs 67.17 h, P = 0.02) with lower postoperative pain score at postoperative day 0 (1.58 vs 4.00, P < 0.01) and day 1 (1.00 vs 2.67, P < 0.01) while having decreased opioid consumption (P < 0.01). The intervention group also had faster recovery of gastrointestinal function. Overall, good compliance to most of the ERAS pathway domains was obtained. CONCLUSION: The ERAS protocol demonstrates benefits on shortening hospital stay, reducing pain, and bowel function recovery without increasing complications in our population. CLINICAL TRIAL REGISTRATION: The present study was registered at clinicaltrials.gov (NCT04201626) on December 3, 2019. Initial participant enrollment began on June 1, 2020. Access through URL of the registration site: https://clinicaltrials.gov/ct2/show/NCT04201626?cond=ERAS&cntry=TH&draw=2&rank=3.

Efficacy of Listening to Music on Pain Reduction during Colposcopy-Directed Cervical Biopsy: A Randomized, Controlled Trial.

Background and Objective: To investigate the efficacy of listening to music on pain reduction during colposcopy-directed cervical biopsy (CDB). Materials and Methods: From June 2020 to November 2021, 240 women undergoing CDB were enrolled. The participants were randomized into three groups: Group 1, colposcopic examination while wearing headphones and listening to music; Group 2, colposcopy while wearing headphones but not listening to music; Group 3 (control group), colposcopy while neither listening to music nor wearing headphones. All participating women completed a 10 cm visual analog scale for subjective pain at three time points: baseline, immediately after cervical biopsy, and 15 min after the procedure. The primary endpoint was the biopsy pain score. Result: Of the 240 women, a sample size of 80 was randomly assigned per group. The clinical-pathological and procedure-related characteristics of the participants in all groups were similar. The mean baseline pain score between each group was not significantly different (2.83 in the music group, 2.54 in group 2, and 2.94 in the control group, p = 0.47). There were no significant differences between each group in terms of mean biopsy pain score (4.21 in the music group, 4.24 in group 2, and 4.30 in the control group, p = 0.98). The differences in changes between the baseline pain score and the biopsy pain score were not statistically significant (1.39 in the music group, 1.70 in group 2, and 1.36 in the control group, p = 0.69). In the multiple comparison analysis, the differences in changes between the biopsy pain score and the baseline pain score between each group were also not statistically significant. There were no complications with the intervention observed. Conclusion: This study demonstrated that there was no beneficial effect of listening to music on pain reduction during colposcopy-directed cervical biopsies.

HIV-Infected Women with Low-Grade Squamous Intraepithelial Lesion on Cervical Cytology Have Higher Risk of Underlying High-Grade Cervical Intraepithelial Neoplasia.

OBJECTIVE: To evaluate the risk of histological high-grade cervical lesions defined as cervical intraepithelial neoplasia grade 2 or worse (CIN2+) in women with human immunodeficiency virus (HIV) infection who had low-grade squamous intraepithelial lesions (LSIL) on cervical cytological screening compared with HIV-uninfected women who had similar cytology. METHODS: 127 HIV-positive women aged 18-65 years with LSIL cytology undergoing colposcopic examination between January 2008 and December 2019 at Chiang Mai University Hospital were reviewed. By matching 1:1 ratio for age (±5 years) and examination time period (±12 months), 127 HIV-negative women with LSIL cytology in the same period were recruited as controlled subjects for comparison. The patients' characteristics, HIV status, CD4 counts, antiretroviral therapy, and histopathology on cervical biopsy were analyzed. RESULTS: HIV-infected women significantly had early sexual debut (age < 20 years) and more sexual partners (≥2) than HIV-uninfected women. The risk of underlying CIN2+ in HIV-infected women was significantly higher than that in HIV-negative women (20.5% vs. 9.4%, p = 0.021) with an odds ratio (OR) of 2.47 and 95% confidence interval (CI) = 1.18-5.14. After adjustment, the risk of underlying CIN2+ in HIV-infected women remained significantly higher than that in HIV-uninfected women (adjusted OR = 2.55, 95% CI = 1.11-5.82, p = 0.027). CONCLUSION: Among women with LSIL on cervical cytology, the risk of underlying CIN2+ in HIV-infected women was approximately 2.5 times higher than those without HIV infection. Colposcopy is indicated particularly in the case of women with a long duration of HIV infection.

Risk of High-Grade Cervical Lesions in Atypical Squamous Cells of Undetermined Significance (ASC-US) Cytology: Comparison between HIV-Infected and HIV-Negative Women.

BACKGROUND AND OBJECTIVE: Women with human immunodeficiency virus (HIV) infection have an increased risk of HPV infection, cervical neoplasia. This study was undertaken to compare the risk of having high-grade cervical lesions defined as cervical intraepithelial neoplasia grade 2 or worse (CIN2+) in HIV-infected versus HIV-uninfected women who had atypical squamous cells of undetermined significance (ASC-US) on cervical cytology. METHODS: Fifty-seven HIV-positive women aged 25-65 years with ASC-US cytology undergoing colposcopic examination between January 2008 and December 2020 at Chiang Mai University Hospital were reviewed. By matching 1:5 ratio, 285 HIV-negative women with ASC-US cytology in the same period were recruited as controlled subjects for comparison. The patient characteristics, HIV status, CD4 cell count within 6 months of colposcopy, antiretroviral therapy, parity, contraception, smoking history, number of sexual partners, and histopathology on cervical biopsy were analyzed. RESULTS: Mean age ± SD of the HIV-positive and HIV-negative groups was 44.28 ± 8.53 years and 44.28 ± 9.68 years, respectively. HIV-positive women were significantly less likely to use contraceptive methods (36.8 % versus 48.8 % in HIV-negative women; P = 0.002). HIV-infected women significantly had more sexual partners than HIV-uninfected women. Both groups had similar risk for CIN 2+ (5.3 % in HIV-positive women compared with 4.9 % in HIV-negative women; odds ratio [OR] = 1.08, 95% confidence interval [CI] = 0.30 -3.87). After adjustment for no contraception use and number of sexual partners, the risk of CIN2+ in HIV-infected women remained unchanged; adjusted OR= 1.15, 95% CI = 0.27-4.92, P= 0.846). CONCLUSION: The risk of underlying high-grade cervical lesions in women with ASC-US on cervical cytology was approximately 5 %, regardless of HIV status.

Pulmonary Recruitment Maneuver for Reducing Shoulder Pain after Laparoscopic Gynecologic Surgery: A Network Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Shoulder pain is a common symptom following laparoscopic surgery. This systematic review was undertaken to assess updated evidence regarding the effectiveness and complications of the pulmonary recruitment maneuver (PRM) for reducing shoulder pain after laparoscopic gynecologic surgery. METHODS: A number of databases for randomized controlled trials (RCTs) investigating PRM for reducing shoulder pain were searched up to June 2019. Two authors independently selected potentially relevant RCTs, extracted data, assessed risk of bias, and compared results. Network meta-analyses were employed to simultaneously compare multiple interventions. Effect measures were presented as pooled mean difference (MD) or risk ratio (RR) with corresponding 95% confidence intervals (CI). RESULTS: Of the 44 records that we identified as a result of the search (excluding duplicates), eleven RCTs involving 1111 participants were included. Three studies had an unclear risk of selection bias. PRM with a maximum pressure of 40 cm H2O was most likely to result in the lowest shoulder pain intensity at 24 hours (MD -1.91; 95% CI -2.06 to -1.76) while PRM with a maximum pressure of 40 cm H2O plus intraperitoneal saline (IPS) appeared to be the most efficient at 48 hours (MD -2.09; 95% CI -2.97 to -1.21). The estimated RRs for analgesia requirement, nausea/vomiting, and cardiopulmonary events were similar across the competing interventions. CONCLUSION: PRM with 40 cm H2O performed either alone or accompanied by IPS is a promising intervention for alleviating shoulder pain within 48 hours following gynecologic laparoscopy.

Management of drainage for malignant ascites in gynaecological cancer.

BACKGROUND: Ascites is the accumulation of fluid within the abdominal cavity. Most women with advanced ovarian cancer and some women with advanced endometrial cancer need repeated drainage for ascites. Guidelines to advise those involved in the drainage of ascites are usually produced locally and are generally not evidence-based. Managing drains that improve the efficacy and quality of the procedure is key in making recommendations that could improve the quality of life (QoL) for women at this critical period of their lives. OBJECTIVES: To evaluate the effectiveness and adverse events of different interventions for the management of malignant ascites drainage in the palliative care of women with gynaecological cancer. SEARCH METHODS: We searched CENTRAL, MEDLINE, and Embase to 4 November 2019. We checked clinical trial registries, grey literature, reports of conferences, citation lists of included studies, and key textbooks for potentially relevant studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of women with malignant ascites with gynaecological cancer. If studies also included women with non-gynaecological cancer, we planned to extract data specifically for women with gynaecological cancers or request the data from trial authors. If this was not possible, we planned to include the study only if at least 50% of participants were diagnosed with gynaecological cancer. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies, extracted data, evaluated the quality of the included studies, compared results, and assessed the certainty of the evidence using Cochrane methodology. MAIN RESULTS: In the original 2010 review, we identified no relevant studies. This updated review included one RCT involving 245 participants that compared abdominal paracentesis and intraperitoneal infusion of catumaxomab versus abdominal paracentesis alone. The study was at high risk of bias in almost all domains. The data were not suitable for analysis. The median time to the first deterioration of QoL ranged from 19 to 26 days in participants receiving paracentesis alone compared to 47 to 49 days among participants receiving paracentesis with catumaxomab infusion (very low-certainty evidence). Adverse events were only reported among participants receiving catumaxomab infusion. The most common severe adverse events were abdominal pain and lymphopenia (157 participants; very low-certainty evidence). There were no data on the improvement of symptoms, satisfaction of participants and caregivers, and cost-effectiveness. AUTHORS' CONCLUSIONS: Currently, there is insufficient evidence to recommend the most appropriate management of drainage for malignant ascites among women with gynaecological cancer, as there was only very low-certainty evidence from one small RCT at overall high risk of bias.

A randomized controlled trial comparing concurrent chemoradiation versus concurrent chemoradiation followed by adjuvant chemotherapy in locally advanced cervical cancer patients: ACTLACC trial.

OBJECTIVE: To compare response rate and survivals of locally advanced stage cervical cancer patients who had standard concurrent chemoradiation therapy (CCRT) alone to those who had adjuvant chemotherapy (ACT) after CCRT. METHODS: Patients aged 18-70 years who had International Federation of Gynecology and Obstetrics stage IIB-IVA without para-aortic lymph node enlargement, Eastern Cooperative Oncology Group scores 0-2, and non-aggressive histopathology were randomized to have CCRT with weekly cisplatin followed by observation (arm A) or by ACT with paclitaxel plus carboplatin every 4 weeks for 3 cycles (arm B). RESULTS: Data analysis of 259 patients showed no significant difference in complete responses at 4 months after treatment between arm A (n=129) and arm B (n=130): 94.1% vs. 87.0% (p=0.154) respectively. With the median follow-up of 27.4 months, 15.5% of patients in arm A and 10.8% in arm B experienced recurrences (p=0.123). There were no significant differences of overall or loco-regional failure. However, systemic recurrences were significantly lower in arm B than arm A: 5.4% vs. 10.1% (p=0.029). The 3-year progression-free survival (PFS) and 3-year overall survival (OS) of the patients in both arms were not significantly different. The hazard ratio of PFS and OS of arm B compared to arm A were 1.26 (95% CI=0.82-1.96; p=0.293) and 1.42 (95% CI=0.81-2.49; p=0.221) respectively. CONCLUSIONS: ACT with paclitaxel plus carboplatin after CCRT did not improve response rate and survival compared to CCRT alone. Only significant decrease of systemic recurrences with ACT was observed, but not overall or loco-regional failure. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02036164, Thai Clinical Trials Registry Identifier: TCTR 20140106001.

Factors Associated with Development of High-Grade Squamous Intraepithelial Lesions of the Uterine Cervix in Women Younger than 30 Years

Objective: To determine the factors associated with the increased risk of developing high-grade squamous intraepithelial lesions (HSIL) of the uterine cervix in women younger than 30 years compared with those aged ≥ 30 years who also had HSIL. Methods: Patients with HSIL who underwent loop electrosurgical excision procedure (LEEP) between January 2006 and July 2017 at Chiang Mai University Hospital were retrospectively reviewed. We analyzed the factors associated with the development of HSIL by comparing two age groups between women aged < 30 years and those aged ≥ 30 years. The factors analyzed included the well-recognized risk factors for cervical cancer, i.e. age at sexual debut, number of sexual partners, use of oral contraceptive (OC) pills, smoking history, sexually transmitted diseases and HIV status. Univariate and multivariate logistic regressions were used to assess factors associated with the increased risk of developing HSIL in women younger than 30 years compared with those aged ≥ 30 years. Results: During the study period, there were 345 patients with HSIL, 30 were < 30 years (case group) and 315 aged ≥ 30 years (control group). By multivariate analyses , early sexual debut(OR, 2.86; 95% CI, 1.01-8.13; P=0.047), multiple sexual partners (OR, 2.94; 95% CI, 1.23-7.02; P=0.015), history of genital warts (OR, 20.46; 95% CI, 2.27-183.72; P=0.007) and history of smoking (OR, 2.95; 95% CI, 1.10-7.93; P=0.032) were significantly associated with the development of HSIL in women younger than 30 years when compared with those aged ≥ 30 years. The OC use, HIV status and underlying diseases were not significantly different in both groups. Conclusion: Early age at sexual debut, multiple sexual partners, history of genital warts and smoking are significant risk factors for developing HSIL in women younger than 30 years. Cervical cancer screening should be considered in young women with such factors.

Development and Validation of a Predictive Score for Preoperative Diagnosis of Early Stage Epithelial Ovarian Cancer

Objective: To develop and validate a simplified multi-parameter risk-based scoring system for preoperative diagnosis of early stage epithelial ovarian cancer. Methods: All women presented with adnexal mass and were scheduled for operation at Phrapokklao hospital during September 2013 ­ December 2017 were included and categorized according to their histopathologic reports into early stage ovarian cancer groups and benign ovarian tumor groups. Multivariable logistic regression was used to explore for potential predictors. The selected logistic coefficients were transformed into risk-based scoring system. Internal validation was done with bootstrapping procedure. Results: A total of 270 participants were included in analysis and predictive model development, 54 in early stage ovarian cancer group and 216 in benign ovarian tumor group. Menopausal status, two abnormal ultrasound findings (presence of solid component or ascites), tumor size and serum CA-125 level were used for derivation of the scoring system. The score-based model showed area under ROC of 0.88 (95%CI 0.82-0.93). The developed scoring system ranged from 0 to 51 was classified into 3 subcategories for clinical practicability. The positive predictive values for the presence of early stage ovarian cancer were 2.07 (95%CI 0.43-6.05) for low risk patient, 29.13(95%CI 19.65-41.58) for moderate risk patient, and 95.45(95%CI 77.16-99.88) for high risk patient. Conclusion: This simplified risk-based scoring system for preoperative diagnosis of early stage ovarian cancer could aid general physicians or general gynecologists in evaluation of patients presenting with ovarian tumors and help gynecologic oncologists in management planning and prioritization of patients for operation.

Cervical Screening Results Leading to Detection of Adenocarcinoma in Situ of the Uterine Cervix

Background: Adenocarcinoma in situ (AIS) of the uterine cervix is a preinvasive lesion of the invasive adenocarcinoma. We analyzed the cervical screening results leading to detecting the AIS lesions including the coexistence of AIS lesions with high-grade squamous intra-epithelial lesions (HSIL) and invasive carcinoma. Methods: Women who were diagnosed and received treatment for AIS at Chiang Mai University Hospital between January 1, 2007 and August 31, 2016 were retrospectively reviewed. The inclusion criteria were the women who had pathological diagnosis of AIS obtained from cervical punch biopsy or excisional cone biopsy with either loop electrosurgical excision procedure (LEEP) or cold-knife conization (CKC). The patient characteristics, diagnostic work-up and treatment details were reviewed, including the cervical screening results prior to the diagnosis of cervical AIS, pathologic results of excisional cone biopsy and hysterectomy specimens. Results: During the study period, 75 women with AIS pathology undergoing excisional cone biopsy with either LEEP (n=62) or CKC (n=13) were identified. The abnormal cytologic screening leading to detection of AIS was the squamous cell abnormality accounting for 57.3%. Abnormal glandular cytology accounted for 37.3%. The most common abnormal cervical screening results was HSIL cytology (n = 25) followed by AIS cytology (n = 13). Normal cytology was noted in 4 women in whom 3 were positive for HPV 18 and 1 had AIS on the endocervical polyp. AIS coexisted with HSIL and invasive carcinoma were detected in cone biopsy specimens in 21 (28%) and 29 (38.7%) patients, respectively. Conclusion: The majority of cervical screening results leading to detection of cervical AIS was the squamous cell abnormality accounting for 57.3% in which, HSIL cytology was the most common. Abnormal glandular cytology accounted for only 37.3%. Diagnostic cone excision is recommended if AIS lesion is noted in cervical biopsy specimen since nearly 40% have coexisting invasive lesions.

Role of genomic DNA methylation in detection of cytologic and histologic abnormalities in high risk HPV-infected women.

Cervical cancer is the fourth most common malignancy affecting women worldwide. The development of disease is related to high-risk human papillomavirus (hrHPV) infection. Cytology has been the most recommended triage for primary cervical (pre)cancer screening despite relatively low sensitivity. Recently, genomic DNA methylation has been proposed as an additional marker to increase sensitivity for detecting cervical precancerous lesion. This study aimed to evaluate the performance of methylation status of three tumor suppressor genes (CADM1, FAM19A4, and MAL) and HPV genotyping in detection of cytologic and histologic abnormalities in cervical cancer screening. Two hundred and sixty samples with available frozen cell pellets including 70 randomly selected cases of negative for intraepithelial lesion or malignancy (NILM)&HPV-negative, 70 randomly selected cases of NILM&HPV-positive, and 120 cytologic abnormalities & HPV-positive from a population-based cervical cancer screening program (n = 7,604) were investigated for the DNA methylation pattern of CADM1, FAM19A4, and MAL. Of 120 cytologic abnormalities & HPV-positive cases, there were 115 available histologic results. HPV52 and HPV58 were most commonly found in histologic HSIL+. The methylation levels of CADM1, FAM19A4, and MAL were elevated with the severity of cytologic abnormality which significantly increased by 3.37, 6.65 and 2 folds, respectively, in cytologic HSIL comparing with NILM. A significant increase in methylation levels of these three genes was also observed in histologic HSIL+ compared with negative histology but only CADM1 showed a significant higher methylation level than histologic LSIL. Using the ROC curve analysis, DNA methylation levels of FAM19A4 performed best in differentiating high-grade cytology (ASC-H+ from NILM/ASC-US/LSIL), followed by CADM1 and MAL. Whilst the CADM1 methylation performed best in distinguishing histologic HSIL+ from negative/LSIL with an area under the ROC curve of 0.684, followed by MAL (0.663) and FAM19A4 (0.642). Interestingly, after combining high DNA methylation levels to HPV16/18 genotypes, rates of histologic HSIL+ detection were substantially increased from 25% to 79.55% for CADM1, 77.27% for FAM19A4, and 72.73% for MAL, respectively. The rate further increased up to 95.45% when at least one of three genes had a high methylation level. This suggests a possible role of genomic DNA methylation, especially CADM1, in detecting histologic HSIL+ lesions in combination with hrHPV testing.

Perioperative Complications of Hysterectomy After a Previous Cesarean Section: A Systematic Review and Meta-Analysis.

BACKGROUND: With increasing rates of cesarean sections (CS), the number of hysterectomies performed among women with a previous CS is on the rise. OBJECTIVE: To provide the association between the odds of complications following a hysterectomy performed later in life and a previous CS. SEARCH STRATEGY: A comprehensive search was performed using major electronic databases, ie, MEDLINE, Scopus, ISI Web of Science, from their inception to April 2019. SELECTION CRITERIA: Analytical studies, irrespective of language or publication status, were included. DATA COLLECTION AND ANALYSIS: Outcomes were extracted in duplicate. The methodological quality of the included studies was independently evaluated by two review authors. A three-level meta-analysis was applied for outcomes with dependent effect sizes. MAIN RESULTS: Twenty-six studies were included involving 54,815 women. The odds of the following complications were increased in women with a previous CS: urinary tract injury (pooled unadjusted odds ratio (OR)=3.15, 95% CI=2.01-4.94, 15 studies, 33,902 women, and pooled adjusted OR=2.21, 95% CI=1.46-3.34, 3 studies, 31,038 women), gastrointestinal tract injury (pooled unadjusted OR=1.73, 95% CI=1.19-2.53; 7 studies, 30,050, and pooled adjusted OR=1.83, 95% CI=1.11-3.03, 1 study, 25,354 women), postoperative infections (pooled unadjusted OR=1.44, 95% CI=1.22-1.71, 6 studies, 37,832 women), wound complications (pooled unadjusted OR=2.24, 95% CI=1.94-2.57, 9 studies, 37,559 women), reoperation (pooled unadjusted OR=1.46, 95% CI=1.19-1.78, 2 studies, 9,899 women), and blood transfusion (pooled unadjusted OR=1.35, 95% CI=1.03-1.76, 7 studies, 13,430 women). CONCLUSION: Previous CS increases risks of various complications following hysterectomy. This information reminds the gynecologists to be aware of the associations between previous CS and potential complications among women undergoing hysterectomy. PROSPERO REGISTRATION NUMBER: CRD42018085061.

Human Papillomavirus in Thai Women and Men with Anogenital Warts.

OBJECTIVE: Anogenital warts are caused by human papillomavirus (HPV). Globally, HPV genotypes 6 and 11 are most often associated with anogenital warts. However, the diversity of HPV genotypes found in patients with genital warts in Thailand is unknown. The aim of this study was to investigate HPV-associated anogenital warts in the Thai population and to assess whether genotypes found are represented in the bivalent and quadrivalent HPV vaccine. METHODS: This study included 206 anogenital swab samples from patients who were diagnosed with anogenital warts. Detection of HPV DNA was performed using polymerase chain reaction to amplify the L1 gene and sequencing. RESULTS: HPV was identified in 88.3% (182/206) of the samples. The majority of HPV genotypes were low-risk genotypes HPV6 (36.9%) and HPV11 (36.4%), which represented the most common infection found in genital warts in this study. CONCLUSION: Immunization with the quadrivalent vaccine (HPV6, HPV11, HPV16, and HPV18) could potentially prevent genital warts caused by HPV infection.

Effect of lidocaine spray during colposcopy-directed cervical biopsy: A randomized controlled trial.

AIM: We aimed to examine the effect of lidocaine spray in reducing pain during colposcopy-directed cervical biopsy (CDB). METHODS: Two hundred women with abnormal cervical screening test results and abnormal colposcopic findings that required a CDB during April to December 2015 were enrolled. The participants were randomly assigned into one of two groups. For group 1 (lidocaine group), 10% lidocaine spray was applied thoroughly to the ectocervix. For group 2, no anesthesia was given. The primary outcome of this study was the biopsy pain score. RESULTS: Of the 200 women enrolled, 100 were randomly assigned to group 1 and 100 were in group 2. The baseline, biopsy, and postprocedure pain scores were comparable between the study groups. The mean difference between the biopsy and the baseline pain scores and the mean difference of the postprocedure pain scores from baseline were statistically significantly higher in the no-anesthesia group (group 2), P = 0.01 and P = 0.02, respectively. However, the degree of pain was minimal in both groups. There were no complications observed in any participants. CONCLUSION: Lidocaine spray reduces pain during colposcopy-directed cervical biopsy; however, the clinically meaningful effect of such a procedure cannot be demonstrated in this study.

Anti-aging and tyrosinase inhibition effects of Cassia fistula flower butanolic extract.

BACKGROUND: Natural products made from plant sources have been used in a variety of cosmetic applications as a source of nutrition and as a whitening agent. The flowers of Cassia fistula L, family Fabaceae, have been used as a traditional medicine for skin diseases and wound healing and have been reported to possess anti-oxidant properties. The anti-aging effect of C. fistula flower extract on human skin fibroblast was investigated. METHODS: The butanolic extraction of C. fistula flowers was completed and the active compounds were classified. The cytotoxicity of fibroblasts was evaluated by SRB assay for the purposes of selecting non-toxic doses for further experiments. The collagen and hyaluronic acid (HA) synthesis was then measured using the collagen kit and ELISA, respectively. Moreover, the enzyme activity, including collagenase, matrixmelloproteinase-2 (MMP-2) and tyrosinase, were also evaluated. RESULTS: It was found that the flower extract did not affect skin fibroblast cell growth (IC50 > 200 µg/mL). The results did show that the flower extract significantly increased collagen and HA synthesis in a dose dependent manner. The flower extract (50-200 µg/mL) also significantly inhibited collagenase and MMP-2 activity. Furthermore, this flower extract could inhibit the tyrosinase activity that causes hyperpigmentation, which induces skin aging. CONCLUSIONS: The C. fistula flower extract displayed a preventive effect when used for anti-aging purposes in human skin fibroblasts and may be an appropriate choice for cosmetic products that aim to provide whitening effects, and which are designated as anti-aging facial skin care products.