Gaetano Riemma

Endometrial cancer in asymptomatic postmenopausal women: the importance of a rapid, nonharmful, and noninvasive diagnosis

Risk of endometrial cancer in asymptomatic postmenopausal women in relation to ultrasonographic endometrial thickness: a reply to unfounded concerns

Endometrial biopsy: Indications, techniques and recommendations. An evidence-based guideline for clinical practice

This practice guideline provides updated evidence for the gynecologist who performs endometrial biopsy (EB) in gynecologic clinical practice. An international committee of gynecology experts developed the recommendations according to AGREE Reporting Guideline. An adequate tissue sampling is mandatory when performing an EB. Blind methods should not be first choice in patients with suspected endometrial malignancy. Hysteroscopy is the targeted-biopsy method with highest diagnostic accuracy and cost-effectiveness. Blind suction techniques are not reliable for the diagnosis of endometrial polyps. In low resources settings, and in absence of the capacity to perform office hysteroscopy, blind techniques could be used for EB. Hysteroscopic punch biopsy allows to collect only limited amount of endometrial tissue. grasp biopsy technique should be considered first choice in reproductive aged women, bipolar electrode chip biopsy should be preferred with hypotrophic or atrophic endometrium. EB is required for the final diagnosis of chronic endometritis. There is no consensus regarding which endometrial thickness cut-off should be used for recommending EB in asymptomatic postmenopausal women. EB should be offered to young women with abnormal uterine bleeding and risk factors for endometrial carcinoma. Endometrial pathology should be excluded with EB in nonobese women with unopposed hyperestrogenism. Hysteroscopy with EB is useful in patients with abnormal bleeding even without sonographic evidence of pathology. EB has high sensitivity for detecting intrauterine pathologies. In postmenopausal women with uterine bleeding, EB is recommended. Women with sonographic endometrial thickness > 4 mm using tamoxifen should undergo hysteroscopic EB.

Risk of endometrial cancer in asymptomatic postmenopausal women in relation to ultrasonographic endometrial thickness: look but do not overlook

Risk of endometrial cancer in asymptomatic postmenopausal women in relation to ultrasonographic endometrial thickness: a dutiful reply

Risk of endometrial cancer in asymptomatic postmenopausal women in relation to ultrasonographic endometrial thickness: systematic review and diagnostic test accuracy meta-analysis

This study aimed to evaluate the risk of endometrial carcinoma and atypical endometrial hyperplasia in asymptomatic postmenopausal women concerning the endometrial thickness measured by stratified threshold categories used for performing subsequent endometrial sampling and histologic evaluation. MEDLINE, Scopus, ClinicalTrials.gov, SciELO, Embase, the Cochrane Central Register of Controlled Trials, LILACS, conference proceedings, and international controlled trials registries were searched without temporal, geographic, or language restrictions. Studies were selected if they had a crossover design evaluating the risk of atypical endometrial hyperplasia and endometrial carcinoma in postmenopausal asymptomatic women and calculated the diagnostic accuracy of transvaginal ultrasonography thresholds (at least 3.0 mm) confirmed by histopathologic diagnosis. This was a systematic review and diagnostic test accuracy meta-analysis according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses of Diagnostic Test Accuracy and Synthesizing Evidence from Diagnostic Accuracy Tests guidelines. Endometrial thickness thresholds were grouped as follows: from 3.0 to 5.9 mm; between 6.0 and 9.9 mm; between 10.0 and 13.9 mm; and ≥14.0 mm. Quality assessment was performed using the Quality Assessment Tool for Diagnostic Accuracy Studies 2 tool. Publication bias was quantified using the Deek funnel plot test. Coprimary outcomes were the risk of atypical endometrial hyperplasia or endometrial carcinoma according to the endometrial thickness and diagnostic accuracy of each threshold group. A total of 18 studies provided the data of 10,334 women who were all included in the final analysis. Overall, at an endometrial thickness threshold of at least 3.0 mm, the risk of atypical endometrial hyperplasia or endometrial carcinoma was increased 3-fold relative to women below the cutoff (relative risk, 3.77; 95% confidence interval, 2.26-6.32; I Both low and high endometrial thickness thresholds in postmenopausal asymptomatic women seem equally effective in detecting endometrial carcinoma and atypical endometrial hyperplasia. However, although using a 3.0 to 5.9 mm cutoff results in a lower specificity, the offsetting improvement in sensitivity may justify using this cutoff for further endometrial evaluation in patients with suspected endometrial malignancy.

Influence of uterine manipulator on oncological outcome in minimally invasive surgery of endometrial cancer: A systematic review and meta-analysis

The endoscopic approach for early-stage endometrial cancer (EC) treatment is considered gold standard. Some authors expressed their concern regarding uterine manipulator (UM) as a risk factor for tumor spillage and dissemination allowing peritoneal or lympho-vascular spaces invasion (LVSI). This meta-analysis aimed to evaluate the effect of UM on the presence of LVSI, recurrence rate and presence of atypical or malignant peritoneal cytology in patients with endometrial cancer. We searched electronic databases including PubMed, MEDLINE, Embase, Scopus, EBSCO, Google Scholar, and ClinicalTrials.gov. The pooled results were used to evaluate the association between the use of UM and oncological outcomes. This systematic review was reported according to PRISMA statement 2020. Statistical meta-analysis was performed using Review Manager software. This systematic review included 18 studies (3 prospective studies, 13 retrospective studies, and 2 RCT). The pooled results showed no significant difference (RR: 0.86, 95% CI, 0.69 to 1.08) in the incidence of LVSI between manipulated hysterectomy and total abdominal hysterectomy (TAH) and between UM group and non-UM group in minimally invasive surgery (RR: 1.18, 95% CI, 0.76 to 1.85), no significant difference in the rate of recurrence (RR: 1.11, 95% CI, 0.71 to 1.74), in the incidence of positive peritoneal cytology between manipulated and non-manipulated hysterectomies in minimally invasive surgery (RR: 1.89, 95% CI, 0.74 to 4.83) and before and after the use of uterine manipulator (RR: 1.21, 95% CI, 0.68 to 2.16). We found a positive association between malignant cytology and hysterectomies in which a uterine manipulator had been used in a sub-group analysis where LH/LAVH were compared to TAH. (RR = 2.26, 95% CI, 1.08-4.71. P = 0.03). This meta-analysis supports that the use of uterine manipulator for minimally invasive treatment of endometrial cancer does not increase the rate of recurrence and LVSI. Therefore, the opportunity of any other studies on its use in endometrial cancer women should be questioned.

Reproductive Outcomes in Young Women with Early-Stage Cervical Cancer Greater than 2 cm Undergoing Fertility-Sparing Treatment: A Systematic Review

Background and Objectives: Despite advancements in detection and treatment, cervical cancer remains a significant health concern, particularly among young women of reproductive age. Limited data exists in the literature regarding fertility-sparing treatment (FST) of cervical cancers with tumor sizes greater than 2 cm. The objective of this systematic review was to evaluate the reproductive outcomes of women diagnosed with cervical cancer greater than 2 cm who underwent FST. Materials and Methods: A comprehensive search of the literature was carried out on the following databases: MEDLINE, EMBASE, Global Health, The Cochrane Library (Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Cochrane Methodology Register), the Health Technology Assessment Database, and Web of Science. Only original studies (retrospective or prospective) that reported reproductive outcomes of patients with cervical cancer >2 cm were considered eligible for inclusion in this systematic review (CRD42024521964). Studies describing only the oncologic outcomes, involving FST for cervical cancers less than 2 cm in size, and case reports were excluded. Results: Seventeen papers that met the abovementioned inclusion criteria were included in the present systematic review. In total, 443 patients with a cervical cancer larger than 2 cm were included in this systematic review. Eighty pregnancies occurred, with 24 miscarriages and 54 live births. Conclusions: FST appears to be a viable option for women of childbearing age diagnosed with cervical cancer larger than 2 cm. However, careful consideration is advised in interpreting these encouraging results, as they are subject to limitations, such as variability in study designs and potential biases. In addition, reproductive outcomes should be further cross-referenced with oncologic outcomes to clarify the potential risk–benefit ratio. It is critical to conduct further research using standardized approaches and larger participant groups to strengthen the validity of the conclusions drawn.

The Role of β1 Integrin/CD29 as a Potential Prognostic Factor for the Risk of Progression to Cervical Carcinoma in HPV-Associated Lesions

Background and Objectives: Available evidence reports the overexpression of β1 integrin in dysplastic rather than normal cervical tissue. We aimed to evaluate the involvement of β1 (CD29) integrin in the progressive pathogenesis of cervical intraepithelial neoplasia (CIN). Materials and Methods: From January 2019 to December 2021, we prospectively enrolled women undergoing a colposcopy with a cervical biopsy for abnormal cervical cytology and/or undefined cytology with a positive HPV DNA test and women with relapsing cervical inflammatory disorders. Based on the histopathological results, women were divided into four groups: group A (CIN1), group B (CIN2), group C (CIN3), and group D (no CIN diagnosis) as a control group. Subsequently, cytofluorimetry and immunohistochemical analysis (based on the identified positive cell ratios as follows: ≤10%, negative; 10–25%, 1+ (weak); 25–50%, 2+ (medium); ≥50%, and 3+ (high)) for β1 integrin were carried out. Results: In total, 154 women were included. The average fluorescence intensity in the four groups was 2.35 ± 1.37, 2.73 ± 1.56, 3.09 ± 1.56, and 2.13 ± 1.25 UA from groups A to D, respectively; this figure was significantly different for CIN3 (group C) women relative to the other groups (p = 0.0132). Higher β1 integrin/CD29 concentrations in the CIN groups with HR-HPV 16 and 18 were also detected (p = 0.0292, 0.0367, and 0.0357 respectively for CIN3, CIN2, and CIN1). Immunohistochemistry analysis showed higher results for the CIN3 group compared to controls and all the other groups (p < 0.001). Conclusions: β1/CD29 integrin expression increased with CIN grade, and it was significantly higher in CIN3 lesions. This could be used as a promising screening tool to identify women prone to developing high-grade cervical lesions. However, additional evidence is needed to strengthen these findings.

New Perspectives in Therapeutic Vaccines for HPV: A Critical Review

Human Papillomavirus is the main cause of cervical cancer, including squamous cell carcinoma of the oropharynx, anus, rectum, penis, vagina, and vulva. In recent years, considerable effort has been made to control HPV-induced diseases using either prophylactic or therapeutic approaches. A critical review of the literature about the therapeutic Human Papillomavirus vaccine was performed to analyze its efficacy in the treatment of female lower genital tract lesions and its possible perspective application in clinical practice. The most important medical databases were consulted, and all papers published from 2000 until 2021 were considered. We retrieved a group of seven papers, reporting the role of anti HPV therapeutic vaccines against the L2 protein in the order of their efficacy and safety in female lower genital tract disease. In addition, the immune response due to vaccine administration was evaluated. The development of therapeutic vaccines represents an interesting challenge for the treatment of HPV infection of the lower genital tract. Literature data underline that the L2 protein may be an interesting and promising target in the development of therapeutic HPV vaccines, but the possible strengths and the unclear longevity of L2 immune responses are factors to be considered before clinical use.

Echinacea angustifolia and Echinacea purpurea Supplementation Combined with Vaginal Hyaluronic Acid to Boost the Remission of Cervical Low-Grade Squamous Intraepithelial Lesions (L-SILs): A Randomized Controlled Trial

Background and Objectives: Echinacea angustifolia and purpurea have known immunomodulatory effects which boost viral clearance, including HPV infection. However, evidence regarding the improvement due to Echinacea-based supplements of cervical HPV-related pathologies is still lacking. The aim of this study is to evaluate the efficacy of Echinacea supplementation on the remission of cervical low-grade squamous intraepithelial lesions (L-SIL). Materials and Methods: A single-blind 1:1:1 parallel randomized controlled trial was conducted at the Colposcopy Unit of a tertiary care referral center. Reproductive-aged women were allocated either to (a) an oral supplement based on Echinacea extracts plus vaginal hyaluronic acid-based soft gel capsules, (b) the Echinacea supplement alone, or (c) vaginal hyaluronic acid-based soft gel capsules alone for 3 months. The primary outcome was the regression of cervical intraepithelial neoplasia (CIN)-1 for each treatment arm at 3, 6 and 12 months after the diagnosis. Secondary outcomes included changes in the epithelialization, pap smear, colposcopic parameters, histological reports, and vaginal health indexes (VHI) in the study groups. Results: 153 women (52 for arm A, 50 for arm B and 51 for arm C) completed the follow-up and were included in the analysis. There were no significant differences in both primary and secondary outcomes for the three groups after 3 months. At the 6-month follow-up, the number of persistent CIN-1 diagnoses was significantly lower in arm A (15/51), rather than in arm B (23/48, p = 0.03) and C (27/49, p = 0.03). Similarly, the same effect was seen after 12 months for treatment A (5/51) relative to B (15/48, p = 0.03) and C (14/48, p = 0.03). Colposcopic, histological and vaginal parameters were all significantly improved at 6 and 12 months for arm A relative to B and C, while no beneficial effects were seen after 3 months. Conclusions: Echinacea extracts supplementation in women with L-SIL/CIN-1 significantly boosts HPV lesion clearance, reducing the overall amount of diagnosis, histological, colposcopic and vaginal parameters after 6 and 12 months. However, a limited sample size reduces the quality of evaluated evidence, emphasizing the need for additional studies to validate these findings.