O-RADS MRI scoring system: key points for correct application in inexperienced hands.

OBJECTIVES: To evaluate the efficacy of the O-RADS MRI criteria in the stratification of risk of malignancy of solid or sonographically indeterminate ovarian masses and assess the interobserver agreement of this classification between experienced and inexperienced radiologists. METHODS: This single-centre retrospective study included patients from 2019 to 2022 with sonographically indeterminate or solid ovarian masses who underwent MRI with a specific protocol for characterisation according to O-RADS MRI specifications. Each study was evaluated using O-RADS lexicon by two radiologists, one with 17 years of experience in gynaecological radiology and another with 4 years of experience in general radiology. Findings were classified as benign, borderline, or malignant according to histology or stability over time. Diagnostic performance and interobserver agreement were assessed. RESULTS: A total of 183 patients with US indeterminate or solid adnexal masses were included. Fifty-seven (31%) did not have ovarian masses, classified as O-RADS 1. The diagnostic performance for scores 2-5 was excellent with a sensitivity, specificity, PPV, and NPV of 97.4%, 100%, 96.2%, and 100%, respectively by the experienced radiologist and 96.1%, 92.0%, 93.9%, and 94.8% by the inexperienced radiologist. Interobserver concordance was very high (Kappa index 0.92). Almost all the misclassified cases were due to misinterpretation of the classification similar to reports in the literature. CONCLUSION: The diagnostic performance of O-RADS MRI determined by either experienced or inexperienced radiologists is excellent, facilitating decision-making with high diagnostic accuracy and high reproducibility. Knowledge of this classification and use of assessment tools could avoid frequent errors due to misinterpretation. CRITICAL RELEVANCE STATEMENT: Up to 31% of ovarian masses are considered indeterminate by transvaginal US and 32% of solid lesions considered malignant by transvaginal US are benign. The O-RADs MRI accurately classifies these masses, even when used by inexperienced radiologists, thereby avoiding incorrect surgical approaches. KEY POINTS: • O-RADS MRI accurately classifies indeterminate and solid ovarian masses by ultrasound. • There is excellent interobserver agreement between experienced and non-experienced radiologists. • O-RADS MRI is a helpful tool to assess clinical decision-making in ovarian tumours.

Assessing vaginal wall thickness by transvaginal ultrasound in breast cancer survivors: A pilot study.

AIM: There is need for a straightforward objective measure to evaluate vaginal wall changes related to hypoestrogenism. The aim of this pilot study was to evaluate a transvaginal ultrasound procedure for the quantification of vaginal wall thickness in order to differentiate between healthy premenopausal women and postmenopausal women with genitourinary syndrome of menopause using ultra-low-level estrogen status as a model. METHODS: We performed a prospective, two-arm, cross-sectional pilot study comparing vaginal wall thickness measured by transvaginal ultrasound in postmenopausal breast cancer survivors using aromatase inhibitors with genitourinary syndrome of menopause (GSM group) and healthy premenopausal women (control or C group) from October 2020 to March 2022. After intravaginal introduction of 20 cm3 of sonographic gel, vaginal wall thickness was measured by transvaginal ultrasound in the anterior, posterior, and right and left lateral walls (four quadrants). The study methods followed the STROBE checklist. RESULTS: According to the results of a two-sided t-test, the mean vaginal wall thickness of the four quadrants in the GSM group was significantly less than that of the C group (2.25 mm vs 4.17 mm, respectively; p < 0.001). Likewise, the thickness of each of the vaginal walls (anterior, posterior, right and left lateral) statistically differed between the two groups (p < 0.001). CONCLUSION: Transvaginal ultrasound with intravaginal gel may be a feasible objective technique to assess genitourinary syndrome of menopause, showing clear differences in vaginal wall thickness between breast cancer survivors using aromatase inhibitors and premenopausal women. Possible correlations with symptoms or treatment response should be assessed in future studies.

Comparison of HE4, CA125, ROMA and CPH-I for Preoperative Assessment of Adnexal Tumors.

(1) OBJECTIVE: To assess the performance of CA125, HE4, ROMA index and CPH-I index to preoperatively identify epithelial ovarian cancer (EOC) or metastatic cancer in the ovary (MCO). (2) METHODS: single center retrospective study, including women with a diagnosis of adnexal mass. We obtained the AUC, sensitivity, specificity and predictive values were of HE4, CA125, ROMA and CPH-I for the diagnosis of EOC and MCO. Subgroup analysis for women harboring adnexal masses with inconclusive diagnosis of malignancy by ultrasound features and Stage I EOC was performed. (3) RESULTS: 1071 patients were included, 852 (79.6%) presented benign/borderline tumors and 219 (20.4%) presented EOC/MCO. AUC for HE4 was higher than for CA125 (0.91 vs. 0.87). No differences were seen between AUC of ROMA and CPH-I, but they were both higher than HE4 AUC. None of the tumor markers alone achieved a sensitivity of 90%; HE4 was highly specific (93.5%). ROMA showed a sensitivity and specificity of 91.1% and 84.6% respectively, while CPH-I showed a sensitivity of 91.1% with 79.2% specificity. For patients with inconclusive diagnosis of malignancy by ultrasound features and with Stage I EOC, ROMA showed the best diagnostic performance (4) CONCLUSIONS: ROMA and CPH-I perform better than tumor markers alone to identify patients harboring EOC or MCO. They can be helpful to assess the risk of malignancy of adnexal masses, especially in cases where ultrasonographic diagnosis is challenging (stage I EOC, inconclusive diagnosis of malignancy by ultrasound features).

Detection of the sentinel lymph node with hybrid tracer (ICG-[99mTc]Tc-albumin nanocolloid) in intermediate- and high-risk endometrial cancer: a feasibility study.

PURPOSE: Indocyanine green (ICG) is frequently used for the detection of the sentinel lymph node (SLN) in gynecology, but it carries the loss of the presurgical SLN mapping provided by [99mTc]-based colloids. Hybrid tracers such as ICG-[99mTc]Tc-albumin nanocolloid combine the benefits of both components. The aim of this study was to evaluate the feasibility and applicability of this hybrid tracer injected by transvaginal ultrasound-guided myometrial injection of radiotracer (TUMIR) approach in the detection of SLNs in patients with intermediate- and high-risk EC. METHODS: Fifty-two patients with intermediate- and high-risk EC underwent SLN biopsy after injection of a hybrid tracer using the TUMIR approach, followed by pelvic and paraaortic lymphadenectomy. SLNs were detected preoperatively by lymphoscintigraphic study and intraoperatively by gamma probe and near-infrared (NIR) optical laparoscopic camera. RESULTS: Preoperative lymphatic drainage was obtained in 69% and intraoperative detection in 71.4% of patients. A total of 146 SLNs (4.17 SLNs/patient) were biopsied. Pelvic bilateral detection was observed in 57% of the women and paraaortic drainage in 34% of the patients. The radioactive component allowed the detection of SLN in 97.1% of the patients, while the fluorescent component detected 80%. In more than 17% of the patients with intraoperative detection, SLNs were detected only by the radioactive signal. Lymph node metastasis was identified in 14.3% of patients submitted to SLNB. The sensitivity and negative predictive value for metastatic involvement were 100%. CONCLUSION: TUMIR injection of a hybrid tracer in patients with intermediate- and high-risk EC combines the benefits of the radiotracer and the fluorescence methods with a single tracer. The method increases the paraaortic detection rate and allows a potential increase in SLN detection. Notwithstanding, based on our findings, the radioactive component of the hybrid tracer cannot be obviated.

Molecular Landscape of Vulvar Squamous Cell Carcinoma.

Vulvar squamous cell carcinoma (VSCC) is a rare malignancy with dual pathogenesis, Human papillomavirus (HPV)-associated and HPV-independent, with a poorly explored molecular landscape. We aimed to summarize the findings of the series analyzing molecular hallmarks of this neoplasm. In January 2021, we conducted a comprehensive literature search using Pubmed Medline and Scopus to identify publications focused on genomic profiling of VSCC. Observational studies, including both prospective and retrospective designs, evaluating molecular alterations in VSCC were deemed eligible. A total of 14 studies analyzing 749 VSCC were identified. The study series were heterogeneous in HPV testing and sequencing strategies, included small sets of tumors and cancer genes, and commonly lacked survival analysis. Only one extensive targeted next-generation sequencing-based study comprised a large cohort of 280 VSCC. The mutated genes, their number, and frequencies were highly variable between the series. Overall, TP53 and CDKN2A, followed by PIK3CA, HRAS, and PTEN, were the most frequently studied and mutated genes. Mutations involved in the PI3K/AKT/mTOR pathway, including TP53, HRAS, KRAS, and PIK3CA, have been consistently reported across the studies. However, the role of individual mutations or pathways in the development of VSCC remains unclear. In conclusion, heterogeneity and the small sample size of available molecular series contribute to a limited view of the molecular landscape of VSCC. Large-scale genome- or exome-wide studies with robust HPV testing are necessary to improve the molecular characterization of VSCC.

Colposcopic Impression Has a Key Role in the Estimation of the Risk of HSIL/CIN3.

Recently published guidelines stratify the risk of high-grade squamous intraepithelial lesion/grade 3 cervical intraepithelial neoplasia (HSIL/CIN3) based on hrHPV detection and Pap smear results. However, colposcopic impression could also provide valuable information for risk estimation. We aimed to analyze the value of adding colposcopic impression to screening tests for the diagnosis of HSIL/CIN3 in 302 women referred for colposcopy due to an abnormal Pap smear. All women underwent hrHPV detection and genotyping (HPV 16/18 vs. non-16/18 hrHPV), Pap smear, and colposcopy with at least one biopsy. HSIL Pap smear, HPV 16/18, and grade 2 colposcopy findings increased the risk of HSIL/CIN3 in the univariate analysis but only colposcopy retained significance in the multivariate model. At least 30% of the women with grade 2 colposcopy findings had HSIL/CIN3, independent of the screening test results. Among women with an HSIL Pap smear and grade 2 colposcopy findings, 53.3% had HSIL/CIN3 independently of the hrHPV genotype. Contrarily, the prevalence of HSIL/CIN3 in women with

Paraaortic sentinel lymph node detection in intermediate and high-risk endometrial cancer by transvaginal ultrasound-guided myometrial injection of radiotracer (TUMIR).

OBJECTIVE: We aimed to evaluate the accuracy of sentinel lymph node (SLN) mapping with transvaginal ultrasound-guided myometrial injection of radiotracer (TUMIR) to detect lymph node (LN) metastases, in patients with intermediate and high-risk endometrial cancer (EC), focusing on its performance to detect paraaortic involvement. METHODS: Prospective study including women with preoperative intermediate or high-risk EC, according to ESMO-ESGO-ESTRO consensus, who underwent SLN mapping using the TUMIR approach. SLNs were preoperatively localized by planar and single photon emission computed tomography/computed tomography images, and intraoperatively by gamma-probe. Immediately after SLN excision, all women underwent systematic pelvic and paraaortic lymphadenectomy by laparoscopy. RESULTS: The study included 102 patients. The intraoperative SLN detection rate was 79.4% (81/102). Pelvic and paraaortic drainage was observed in 92.6% (75/81) and 45.7% (37/81) women, respectively, being exclusively paraaortic in 7.4% (6/81). After systematic lymphadenectomy, LN metastases were identified in 19.6% (20/102) patients, with 45.0% (9/20) showing paraaortic involvement, which was exclusive in 15.0% (3/20). The overall sensitivity and negative predictive value (NPV) of SLNs by the TUMIR approach to detect lymphatic involvement were 87.5% and 97.0%, respectively; and 83.3% and 96.9%, for paraaortic metastases. After applying the MSKCC SLN mapping algorithm, the sensitivity and NPV were 93.8% and 98.5%, respectively. CONCLUSION: The TUMIR method provides valuable information of endometrial drainage in patients at higher risk of paraaortic LN involvement. The TUMIR approach showed a detection rate of paraaortic SLNs greater than 45% and a high sensitivity and NPV for paraaortic metastases in women with intermediate and high-risk EC.

Diagnosis and Surgical Treatment of Uterine Isthmus Atresia: A Case Report and Review of the Literature.

Uterine isthmus atresia is a rare Müllerian duct anomaly occasionally diagnosed in adolescents with primary amenorrhea and cyclic abdominal pain. A case is presented of a 14-year-old female with monthly cyclic lower abdominal pain of a 2-year duration. Magnetic resonance imaging and 3-dimensional ultrasound showed separation of a 10-mm fibrotic tissue between the cervical canal and the endometrial cavity. In an attempt to preserve reproductive ability, an end-to-end anastomosis was laparoscopically performed between the cervical canal and uterine cavity. A platinol stent (WallFlex Biliary RX; Boston Scientific, Boston, MA) was placed by hysteroscopy to avoid stenosis after surgery. Laparoscopic end-to-end anastomosis is proposed to treat congenital uterine isthmus atresia.

p53 Immunohistochemical Patterns in HPV-Independent Squamous Cell Carcinomas of the Vulva and the Associated Skin Lesions: A Study of 779 Cases.

Human papillomavirus (HPV)-independent vulvar squamous cell carcinomas (VSCC) and its precursors frequently harbour TP53 mutations. Recently, six p53 immunohistochemical (IHC) patterns have been defined, which have shown strong correlation with TP53 mutation status. However, few studies have applied this new six-pattern framework and none of them exhaustively compared p53 IHC positivity and patterns between invasive VSCC and adjacent skin lesion. We performed p53 IHC in a series of 779 HPV-independent VSCC with adjacent skin and evaluated the IHC slides following the newly described classification. Some 74.1% invasive VSCC showed abnormal p53 IHC staining. A skin lesion was identified in 450 cases (57.8%), including 254 intraepithelial precursors and 196 inflammatory/reactive lesions. Two hundred and ten of 450 (47%) VSCC with associated skin lesions showed an abnormal p53 IHC stain, with an identical staining pattern between the VSCC and the adjacent skin lesion in 80% of the cases. A total of 144/450 (32%) VSCC showed wild-type p53 IHC both in the invasive VSCC and adjacent skin lesion. Finally, 96/450 (21%) VSCC showed p53 IHC abnormal staining in the invasive VSCC but a wild-type p53 staining in the skin lesion. Most of the discordant cases (70/96; 73%) showed adjacent inflammatory lesions. In conclusion, the p53 IHC staining and pattern are usually identical in the VSCC and the intraepithelial precursor.

HPV Vaccination as Adjuvant to Conization in Women with Cervical Intraepithelial Neoplasia: A Study under Real-Life Conditions.

Background: Recent studies have shown preliminary evidence that vaccination against human papillomavirus (HPV) could decrease the risk of persistent/recurrent HSIL in women treated for high-grade cervical intraepithelial lesion (HSIL). We aimed to determine the benefits of HPV vaccination in patients undergoing conization for HSIL in real-life conditions and evaluate vaccination compliance associated with different funding policies. Methods: From January 2013 to July 2018, 265 women underwent conization in our center. From January 2013 to July 2017, treated patients (n = 131) had to pay for the vaccine, whereas after July 2017 the vaccine was publicly funded and free for treated women (n = 134). Post-conization follow-up controls were scheduled every six months with a Pap smear, HPV testing, and a colposcopy. Results: 153 (57.7%) women accepted vaccination (vaccinated group), and 112 (42.3%) refused the vaccine (non-vaccinated group). Persistent/recurrent HSIL was less frequent in vaccinated than in non-vaccinated women (3.3% vs. 10.7%, p = 0.015). HPV vaccination was associated with a reduced risk of persistent/recurrent HSIL (OR 0.2, 95%CI: 0.1-0.7, p = 0.010). Vaccination compliance increased when the vaccine was publicly funded (from 35.9% [47/131] to 79.1% [106/134], p < 0.001). Conclusions: HPV vaccination in women undergoing conization is associated with a 4.5-fold reduction in the risk of persistent/recurrent HSIL. Vaccination policies have an important impact on vaccination compliance.

Colposcopy Evaluation at the Time of Loop Electrosurgical Excision Procedure May Avoid Unnecessary Treatment.

OBJECTIVE: The aim of the study was to assess the accuracy of colposcopy evaluation at the time of the loop electrosurgical excision procedure (LEEP) to identify women with a previous confirmatory diagnosis of squamous intraepithelial lesion/cervical intraepithelial neoplasia (SIL/CIN) with low probability of dysplasia in the LEEP specimen. MATERIALS AND METHODS: We prospectively recruited a cohort of 162 women undergoing LEEP for histological high-grade SIL/CIN 2-3 or low-grade SIL/CIN 1 with high-grade SIL cytology showing a fully visible squamocolumnar junction in the colposcopy evaluation at the time of LEEP. At the referral visit cervical cytology, human papillomavirus and genotype detection, digital colposcopy, colposcopical lesion measurement, and 1 or more biopsies of the transformation zone were obtained. The uterine cervix was colposcopically evaluated intraoperatively. RESULTS: Thirty-four women (21.0%) had a normal colposcopy evaluation at the time of the LEEP, whereas the remaining 128 women showed abnormal findings. Absence of SIL/CIN in the LEEP specimen was confirmed in 28 (82.3%) of the 34 women with a normal colposcopy at the time of LEEP group and 8 (3.1%) of the 128 women showing abnormal colposcopy at the time of LEEP group (p < .001). A normal colposcopic evaluation at the time of LEEP was associated with an increase in the risk of absence of lesion in the cone specimen compared with cases presenting an abnormal colposcopy (95% CI = 33.8-1,555.1, p < .001). The colposcopy evaluation at the time of LEEP had a positive predictive value of 82.3% (95% CI = 66.5-91.5) and a negative predictive value of 96.9% (95% CI = 92.2-98.8) to predict low probability of SIL/CIN in the specimen. CONCLUSIONS: Colposcopic evaluation at the time of LEEP seems to be accurate to identify SIL/CIN postbiopsy regression; thus, its performance would be considered at the time of the treatment.

The use of inhaled sevoflurane during operative hysteroscopy is associated with increased glycine absorption compared to intravenous propofol for maintenance of anesthesia.

STUDY OBJECTIVE: To compare the effects of anesthesia maintenance drugs (inhaled sevoflurane versus intravenous propofol) used in general anesthesia on the absorption of glycine 1.5% solution during hysteroscopy. DESIGN: Prospective comparative study. SETTING: Tertiary care university hospital. PATIENTS: One hundred fifteen women undergoing hysteroscopy. INTERVENTIONS: Women were assigned to receive general anesthesia with inhaled sevoflurane (n = 77) or intravenous propofol (n = 38) to maintain anesthesia. MEASUREMENTS: The primary endpoint was clinically relevant glycine 1.5% absorption (>1000 mL), while secondary endpoints were the median of glycine absorption, operative time, complications and the incidence of discontinuation of the hysteroscopic procedure due to excessive glycine 1.5% absorption. MAIN RESULTS: Maintenance with sevoflurane produced significantly increased absorption of glycine 1.5% solution compared to intravenous anesthesia (264 vs 202 mL, P = .007). Clinically relevant absorption rates (>1000 mL) were observed in the sevoflurane group (P = .04) while none of the women receiving intravenous anesthesia reached this absorption level. No cases of severe post-operative hyponatremia (Na(1+)<125 mmol/L) or adverse events derived from glycine 1.5% absorption were reported. No major complications (such as perforations, severe hemorrhage or infection) were presented during the interventions. CONCLUSIONS: The results of the present study show that the use of inhaled sevoflurane is associated with significantly increased glycine 1.5% absorption compared to intravenous propofol for the maintenance of anesthesia. However, further randomized controlled trials are needed to assess the possible mechanisms and risk factors involved in the higher absorption induced by sevoflurane.

Usefulness of p16/Ki67 immunostaining in the triage of women referred to colposcopy.

BACKGROUND: This study compared the performance of p16/Ki67 dual-staining and human papillomavirus (HPV) testing in women referred to colposcopy and sought to determine the usefulness of a morphological evaluation of the double-stained cells. METHODS: This prospective study included 1123 women (mean age, 35.8 ± 10.9 years) referred to colposcopy from October 2009 to November 2012 due to positive HPV testing or abnormal cytology results (atypical squamous cells of unknown significance, or worse abnormalities). Liquid-based cytology specimens (PreservCyt, Hologic) were used for HPV detection (Hybrid Capture 2 [HC2]; Qiagen) and p16/Ki67 dual-staining (CINtec Plus; Roche-mtm Laboratories). All women underwent histological study. After completion of the study, 18 patients were classified as having cervical cancer (CC), 378 had a high-grade squamous intraepithelial lesion (HSIL), 304 had a low-grade squamous intraepithelial lesion, and 423 were negative. RESULTS: The sensitivity and specificity of p16/Ki67 dual-staining for HSIL/CC were 90.9% (95% confidence interval [CI] = 87.9-93.9) and 72.1 (95% CI = 68.7-75.4), respectively. For HC2, the figures were, respectively, 96.0% (95% CI = 93.9-98.0) and 41.4 (95% CI = 37.7-45.0). The values were high both in women < 30 and ≥ 30 years old (86.9% and 63.3% versus 92.3% and 77.8%, respectively). The addition of a morphological evaluation of the dual-stain-positive cells with establishment of HSIL features as the threshold for a positive reaction increased the specificity (93.5%) but decreased the sensitivity (84.1%). CONCLUSIONS: Use of the molecular markers p16 and Ki67 has higher specificity than HC2 tests for HSIL or CC, which may support p16/Ki67 dual-staining use in the triage of patients referred for abnormal screening results. Morphological evaluation of p16/Ki67-positive cells may have some benefits in women younger than 30 years or with low-grade squamous intraepithelial lesion.

Prognostic role of maternal neutrophil gelatinase-associated lipocalin in women with severe early-onset preeclampsia.

INTRODUCTION: The association between maternal plasma levels of neutrophil gelatinase-associated lipocalin (NGAL) and maternal complications in women admitted with severe early-onset preeclampsia was evaluated. MATERIAL AND METHODS: Plasma levels of NGAL were measured at admission in patients with severe early-onset (presenting before 34 weeks) preeclampsia. The maternal outcome of women with elevated plasma levels was compared with those with normal levels. Maternal complications included eclampsia, HELLP syndrome, acute renal failure, subcapsular hepatic hematoma, pulmonary edema and disseminated intravascular disease. RESULTS: Sixty-seven patients were included. The median NGAL plasma levels in the group of women who subsequently had a complication were significantly higher than in those uncomplicated cases (114.8 vs. 84.2 ng/ml; Mann-Whitney U test p = 0.03). Maternal complications were more common in the elevated (>100 ng/ml) NGAL group (58.3 vs. 25.6%; χ(2) test p = 0.008), with an OR of 4.1 (95% CI 1.4-11.8). After adjustment by gestational age at onset, the association between elevated NGAL plasma levels and maternal complications remained significant (OR 4.2; 95% CI 1.4-12.4). DISCUSSION: Women with severe early-onset preeclampsia are at higher risk of maternal complications if plasma levels of NGAL are elevated.