Journal

Minerva Obstetrics and Gynecology

Papers (36)

Intrauterine adhesions following fibroid surgery: incidence and prevention strategies. A systematic review

The purpose of this review was to provide current evidence of the relationship between fibroid surgery (hysteroscopic, laparoscopic/robotic, open) and the formation of intrauterine adhesions (IUA). A systematic electronic literature search was conducted to provide a survey of the various surgical modalities and their relevant incidence of intrauterine adhesions. Utilizing PRISMA methodology the search identified 23 full text original studies that were included in the analysis. Our analysis identified 2437 cases reported in the international literature whereby the de novo formation of IUAs were systematically assessed with second look hysteroscopy at least 4 weeks and usually up to 3 months after the surgery. In our analysis, out of 1678 hysteroscopic cases the mean incidence was 9.4% for all different techniques, including monopolar or bipolar diathermy, cold loop and radio frequency ablation. The reported numbers for laparoscopic/robotic and open surgery were 399 and 360 cases respectively. The incidence of IUA following endoscopic abdominal surgery was 12.8% and for the traditional open approach (laparotomy) was 18.3%. There is substantial heterogeneity on the reported data regarding risks factors contributing to IUAs; such as fibroid size, location, number as well as uterine cavity breach during abdominal surgery (either open, laparoscopic or robotic). Iatrogenic IUAs following myomectomies are not uncommon and may be implicated in patient morbidity and sub fertility. Further studies are necessary to evaluate the prevention of such sequelae and improve therapeutic outcomes following fibroid surgery.

A case report of uterine leiomyosarcoma: unusual clinical presentation with unilateral hydronephrosis and importance of an appropriate diagnosis

Uterine leiomyosarcoma is a rare malignant gynecologic tumor that arises from the myometrial or endometrial stromal precursor cells. This tumor has the highest prevalence in the pre- and post-is more frequent between 40 and 60 years old. It has a very unfavorable prognosis: only early-stage tumors have an acceptable prognosis; unfortunately, it is often diagnosed accidentally, typically on an advanced stage, when hematological metastases have already spread. Surgery is the main treatment strategy, while systemic treatment and radiotherapy are not recommended due to the lack of results. Since metastatization is mainly hematological, lymphadenectomy is not recommended. Recent progresses have been achieved in advanced and recurrent disease, often inoperable, thanks to new chemotherapies, target therapies and immunotherapies. We reported the case of a 51-year-old woman evaluated for lumbar pain in the right region compatible with renal colic. The ultrasound evaluation revealed right hydronephrosis and the presence of a paraovarian or intraligamentary mass compatible with fibroma. The abdominal CT confirmed the presence of a mass with heterogeneous vascularization. Therefore, the patient underwent laparoscopic surgery to remove the lesion which resulted to be a leiomyosarcoma G2. During the following week the patient underwent a laparoscopic hysterectomy. The first step for differential diagnosis consists in the evaluation of clinicopathological features, followed by the analysis of preoperative imaging. Pelvic MRI represents the gold standard, while CT is used to detect metastases. The main issue is that imaging shows limited ability in differential diagnosis between benign and malign smooth muscle tumor. The definitive diagnosis is confirmed by histological analysis; this implies the necessity of improved attentions on the surgical procedure, which is often performed by steps with prolongation of the treatment pathway. To distinguish which fibroids presents a major risk to be misdiagnosed, some risk scores were developed (rPRESS in 2014 and pLMS in 2019), though actually they are not applied in clinical practice. Uterine leiomyosarcoma (uLMS) is rare but causes several deaths in perimenopausal women due to lack of effective treatments, although target therapies represent a future hope. Furthermore, clinical practice needs support through the development and improvement of diagnostic risk scores and their integration into guidelines.

The role of colposcopy in HPV vaccination era

Colposcopy has traditionally played a crucial role in the assessment and management of abnormal cervical cytology and human papillomavirus (HPV) -related lesions. However, with the reduction in high-risk (HR) HPV types due to vaccination, the role of colposcopy in the HPV vaccination era is being questioned. The aim of this narrative review was to highlight the latest evidence from the world of HPV vaccination and the future role of colposcopy in the HPV vaccination era. PubMed, MEDLINE, Scopus, Web of Science were searched for relevant articles up to June 2024. HPV vaccination may influence colposcopic practice by reducing HR-HPV vaccine type, colposcopy referrals, colposcopic positive predictive value for CIN 2+, and by changing referral patterns, colposcopic performance, and procedures. The relative incidence of HPV-negative adenocarcinoma and its precursors may be increasing, presenting a new challenge that may increase the difficulty of colposcopic assessment. The role of colposcopy in the management of cervical abnormalities will vary according to vaccination status, vaccine type and timing of vaccination. As this evolves, colposcopy will need to adapt to provide optimal care tailored to individual risk profiles and to maintain the key role in cervical cancer prevention that it has acquired over the past decades. There will certainly be a need to improve the quality and performance of colposcopy by reducing inter- and intra-observer variability in colposcopic practice, including more objective patient selection, greater knowledge, expertise and skill, with the aim of achieving reproducible, sensitive and less biased assessment of cervical appearance.

Ultra-radical surgery for advanced ovarian cancer: a retrospective cohort study in a tertiary referral cancer center in the UK

Ovarian cancer is the leading cause of death from gynecological cancer in the UK. The standard of care is a combination of surgery and chemotherapy. The aim of the treatment is the resection of all macroscopic disease. In selected cases of advanced ovarian cancer this is achieved with ultra-radical surgery. However, NICE encourages further research due to low quality evidence on the safety and efficacy of this extensive surgery. The aim of this study was to examine the morbidity and survival rates of ultra-radical surgery for advanced ovarian cancer performed in our unit and compare our findings with the current literature. This is a retrospective study of 39 patients diagnosed with stage IIIA-IV ovarian and primary peritoneal cancer who underwent surgery in our unit between 2012 and 2020. The main outcome measures were the perioperative complications, the disease-free survival, the overall survival rate and the recurrence rate. The study enrolled 39 patients with stages IIIA-IV who were treated in our unit between 2012 and 2020. 21 patients were at stage III (53.8%) whereas 18 (46.1%) at stage IV. 14 patients underwent primary and 25 secondary debulking surgery. Major and minor complications occurred 17.9% and 56.4% of the patients, respectively. Complete cytoreduction following surgery was achieved in 24 cases (61.5%). The mean and the median survival time were 4.8 years and 5 years, respectively. The mean disease-free survival time was 2.9 years while median disease-free survival time was 2 years. Age (P=0.028) and complete cytoreduction (p=0.048) were found to be significantly associated with survival. Primary debulking surgery was significantly associated with lower probability of recurrence (P=0.049). Although the number of patients is relatively small, our study indicates that ultra-radical surgery in centers with high expertise may result in excellent survival rates with an acceptable rate of major complications. All patients in our cohort were operated by an accredited gynecological oncologist and a hepatobiliary general surgeon with a special interest in ovarian cancer. A few cases required input from a colorectal and a thoracic surgeon. We believe that the careful selection of the patients that can benefit from ultra-radical surgery and our model of joint surgery can explain our excellent results. Further research is essential to establish that ultra- radical surgery has an acceptable rate of morbidity for patients with advanced ovarian cancer.

Discussion on cervical cytology in postmenopausal women

Considering the cervix at the climacteric period, important changes take place in the morphology of the epithelium and stroma due to hypoestrogenism. Therefore, the aim of the present study was to compare the presence of transformation zone cells in the cervix of premenopausal and postmenopausal women. In a private laboratory in São Paulo (Brazil) a retrospective analysis of cervical cytology results was performed. A total of 1,026,671 satisfactory cytology tests were evaluated between January 2010 and December 2015. A marked decline in transformation zone cells with age was evident, with a greater decrease in the ≥50 years age groups. Only 35% of women ≥50 years of age had transformation zone cells in cytology, while in those <50 years, the figure was 67.5% (P<0.001). The prevalence of negative cytological results in these two age groups was respectively 89.9% and 95.3%; however, it was observed that the most serious cytological results occurred in the group after menopause. Although cytology is the recommended screening method for cervical cancer in Brazil, the low number of transformation zone cells in cytology in menopausal patients could be less sensitive for screening of dysplasia and cancer. So, we suggest routine high-risk HPV DNA testing, when possible, given that this test is considered more sensitive for detecting cervical lesions in this group of patients. When HPV DNA testing is not possible, cytology should be collected, and for cytology sampling we suggest regular topical estrogenization and use of appropriate technique.

Gynecologic Imaging and Reporting Data System for classifying adnexal masses

To perform a systematic review and meta-analysis of the diagnostic performance of the so-called Gynecologic Imaging and Report Data System (GI-RADS) for classifying adnexal masses. A search for studies reporting about the use of GI-RADS system for classifying adnexal masses from January 2009 to December 2021 was performed in Medline (Pubmed), Google Scholar, Scopus, Cochrane, and Web of Science databases. Pooled sensitivity, specificity, positive and negative likelihood ratios and diagnostic odd ratio (DOR) were calculated. Studies' quality was evaluated using QUADAS-2. We identified 510 citations. Ultimately, 26 studies comprising 7350 masses were included. Mean prevalence of ovarian malignancy was 26%. The risk of bias was high in eight studies for domain "patient selection" and low for "index test," "reference test" domains for all studies. Overall, pooled estimated sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio and DOR of GI-RADS system for classifying adnexal masses were 94% (95% confidence interval [CI]=91-96%), 90% (95% CI=87-92%), 9.1 (95% CI=7.0-11.9), and 0.07 (95% CI=0.05-0.11), and 132 (95% CI=78-221), respectively. Heterogeneity was high for both sensitivity and specificity. Meta-regression showed that multiple observers and study's design explained this heterogeneity among studies. GI-RADS system has a good diagnostic performance for classifying adnexal masses.

Talcum powder induces malignant transformation in normal human primary ovarian epithelial cells

Several studies have linked perineal use of talcum powder to increased risk of ovarian cancer (OC). Here, we determined that exposure to talcum powder induces malignant transformation in human normal ovarian cells. Human primary ovarian epithelial cells (HPOE), ovarian epithelial cells (HOSEpiC), and primary fibroblasts (NF) were treated with either 100 or 500 μg/mL of talcum powder or titanium dioxide (TiO2) as a particulate control for 72 hours before assessment with a cell transformation assay and p53 and Ki-67 immunohistochemistry. Treatment with talcum powder resulted in formation of colonies, indicating cell malignant transformation in a dose dependent manner in ovarian cell lines. No colonies formed in the untreated ovarian cells or control ovarian cells (TiO2 treated) at either dose. There were no colonies formed in talc treated NF cells. Transformed ovarian cells were increased by 11% and 20% in HPOE and 24% and 40% in HOSEpic cells for talcum powder 100 and 500 μg/mL doses, respectively (P2. Importantly, p53 mutant type as well as increased expression of Ki-67 were detected in HPOE and HOSEpic cells when exposed to talcum powder. Exposure to talcum powder induces malignant transformation in ovarian epithelial cells but not in NF cells. These findings represent a direct effect of talcum powder exposure that is specific to normal ovarian cells and further supports previous studies demonstrating an association between the genital use of talcum powder and an increased risk of OC.

Clinics and pathology of Krukenberg tumor: a systematic review and meta-analysis

Krukenberg tumor (KT) is defined as a secondary neoplasm of the ovary. While ovarian metastases account for about 30% of ovarian tumors, KTs are rare, accounting for about 1-2% of the total. The rarity of KT is at least in part responsible for the lack of a precise clinic-pathological characterization of these tumors. Clinically, KT may have a subtle clinical presentation, with few symptomatic manifestations and nonspecific clinical signs, even though in literature there is disagreement about the clinical presentation of these patients; such difficulties in the diagnostic framework often leads to a delayed diagnosis with serious consequences on the patient outcome. We aimed to provide a clinico-pathological characterization of Krukenberg Tumor (KT) through a systematic review and meta-analysis to improve the diagnosis and management of KT. Electronic databases were searched for all studies assessing clinico-pathological features of KT series. Pooled prevalence of each clinical or pathological factor was calculated according to the random-effect model. Forty-eight studies with 3025 KT patients were included; 39.7% of patients were ≥50 and 39.8% were postmenopausal. The most common primary tumor sites were stomach (42.5%), colon-rectum (26.1%), breast (9.3%), and appendix (5%); 48.7% of KTs were synchronous with the primary tumor, 64.3% were bilateral, 40.5% had a diameter ≥10 cm; 55.3% showed extraovarian extent and 49% showed peritoneal involvement. The most common presenting symptoms were ascites (51.7%), palpable mass (31.3%), pain (29.3%), abdominal distention (28.7%), irregular bleeding (9.1%), asymptomatic (11.2%). KT shows a highly variable presentation. Understanding the prevalence of clinico-pathological factors may be helpful to improve the diagnosis and management of KT.

The potential benefits of dinitrophenol combination with chemotherapy in the treatment of ovarian cancer

2,4-dinitrophenol (DNP), an uncoupling mitochondrial agent, has been identified as a source of oxidative stress and linked to the pathogenesis of ovarian cancer. In this study, we determine the cytotoxic effect of DNP alone or in combination with chemotherapies in ovarian cancer cells. We utilized human ovarian cancer cell lines SKOV-3 and MDAH-2774 with their chemoresistant counterparts. Cancer stem cells (CSCs) were isolated from SKOV-3 utilizing magnetic-activated cell sorting technique for CD44+/CD117+ cells. Human normal primary ovarian epithelial (NOEC) and HOSEpiC cell lines were used as a control. Cells were treated with and without chemotherapy (taxotere 0.3 µM or cisplatin 50 µM), with or without increasing doses of DNP (0.125, 0.25, or 0.5 mM) for 24 hours followed by evaluation of cell viability and IC50 utilizing MTT assay. For determination of synergism, Fa-combination Index plots were created using the CompuSyn software (ComboSyn, Inc., Paramus, NJ, USA). All data were run in triplicates and analyzed by t-test. DNP treatment of ovarian cancer and chemoresistant ovarian cancer cell lines as well as CSCs resulted in decreased cell viability in a dose dependent manner with no effect on normal cells. Combination of DNP with chemotherapy synergistically enhances cytotoxicity of chemotherapeutics in all ovarian cancer cells as compared to chemotherapy alone. Our data indicates the potential of the addition of DNP to the arsenal of drugs available to treat ovarian cancer, whether alone or in combination with chemotherapies. The synergistic effects of DNP in reducing the required amount of chemotherapy, is critical for the alleviation of harmful side effects.

Investigating the relationship between the cervical mucoprotein levels and cervical intraepithelial neoplasia

Cervical cancer has been ranked as the fourth most common cancer in women. The role of HPV, the DNA virus identified in the 1980s, in almost all cervical cancers is undisputed. In patients scanned with smear and HPV, a cervical biopsy is performed accompanied by colposcopic examination, and the lesion is defined. The concentration of mucoproteins varies in the structure of the cervical mucus with neoplasms. The major aim of this study was to investigate the changes in the levels of cervical mucoprotein in patients at the early stages of cervical cancer and evaluate if these levels can be used in the early diagnosis of this cancer type. The study was designed as a prospective cohort study. Samples from cervical mucus were taken and stored before colposcopy examination of human papillomavirus (HPV) positive patients (N.=100). According to the pathology results, while 36 cases constituted the precancerous group, no suspicion of cancer was found in 64 cases. To ensure standardization, colposcopy was performed immediately after the menstrual cycle and at least 0.5 mL of the cervical mucus sample was taken from all individual patients used in this study. Cervical mucus samples of the patients were analyzed for mucoproteins MUC1, MUC2, MUC5AC and MUC5B. All mucoprotein levels were found to be higher in patients with cervical intraepithelial neoplasia (CIN) than those of subjects with normal pathology for cervical neoplasia. Significant relationship was obtained between cervical intraepithelial neoplasms and the levels of mucoproteins in cervical mucus. The results showed that diagnosis of neoplasia with HPV may be easily performed by utilizing any mucoprotein test.

How challenging could be preoperative and intraoperative diagnosis of endometrial cancer?

Aim of this study was to rate the misdiagnosis of histological type between preoperative endometrial biopsy and final postoperative pathology focusing on non-endometrioid endometrial cancer (NEEC). Secondary objective is to assess the concordance between intraoperative assessment and final pathology in a subgroup of patients. A multicenter retrospective study was conducted in patients with histological diagnosis of endometrial cancer who underwent surgical staging between 2011 and 2016. The concordance rate and the Kappa Cohen coefficient were calculated to assess the correlation concerning the histological type between endometrial biopsy and final pathology, and between intraoperative assessment and final pathology in a subgroup of patients. Two hundred ninety-five patients were enrolled, 226 were endometrioid carcinomas and 61 NEEC at final pathology. The concordance rate between pre-operative and final pathology for NEEC and the Kappa Cohen coefficient were 81.4% and 0.41 (CI 95% 0.3059-0.5122), respectively. 26 out of 61 (42.6%) NEEC were preoperatively misdiagnosed. The frozen section was performed in a subgroup of 86 patients (29.15%): the concordance rate between frozen section and final pathology for NEEC was 80% and the Kappa Cohen coefficient was 0.28 (CI 95% 0.212-0.347). Preoperative pathological histotype assessment predicts final pathology with a moderate grade of accuracy and the identification of NEEC could be challenging. Efforts should be directed toward molecular characterization of diagnostic samples in order to improve diagnostic accuracy and guide therapeutic decisions.

Therapeutic human papilloma virus vaccination in patients at risk for cervical dysplasia

Shared decision making between patients and their healthcare providers is recommended for use of the human papillomavirus (HPV) vaccine Gardasil 9 (9v-HPV) in women ages 27-45 years. We studied HPV vaccination as a treatment modality for patients undergoing colposcopy older than age 26 years who tested positive for high-risk subtypes of HPV (HR-HPV). A retrospective study (N.=155) was performed for patients that were evaluated for cervical dysplasia who tested positive for HR-HPV and received the 9v-HPV vaccine prior to repeat cervical cancer screening with co-testing. Demographic information, risk factors for cervical dysplasia, and treatment outcomes were assessed for response to vaccination as treatment. Repeat co-testing was negative for HR-HPV in 76 patients (49%) and was positive in 79 patients (51%). A greater percentage of Hispanic patients cleared the virus and Black patients had a greater percentage of persistent HR-HPV on repeat co-testing (P=0.047). When comparing those who cleared the virus and those who had persistent HR-HPV, there were no differences observed for associated risk factors for dysplasia, HPV subtype, cytology or colposcopy results, vaccine dosing interval, or total number of vaccine doses received. While the HPV vaccine is effective for prevention of infection by high-risk strains of HPV, it remains unclear whether 9v-HPV vaccine should be recommended as a treatment option in exposed patients beyond age 26. We recommend healthcare providers discuss usefulness of 9v-HPV vaccine with their unvaccinated patients 27 years and older at risk for cervical dysplasia.

Attitudes of mothers of preadolescent girls on HPV vaccine in Italy: do we need a turning point?

The aim of this study was to investigate the knowledge, awareness, and attitude of mothers of preadolescent girls regarding the HPV vaccination and cervical cancer, and to understand how to improve the efficacy of the Italian vaccination campaign through the gathered data. A questionnaire-based survey was conducted in mothers of unvaccinated 9 to 12-year-old girls in Italy from November 2018 to July 2019, to evaluate their awareness and the attitude toward HPV, its vaccination, and the information sources of the vaccination campaign. The selection of the distribution sites of the questionnaire was performed with randomization of 50 major places of aggregation located throughout the Italian territory. Three hundred mothers of unvaccinated girls were included in the study and divided into two groups (191 subjects 45 years old). Results showed that 79.6% of 45 years old (P value 45 years old) showed awareness about the HPV vaccine (P value 0.03). The percentage of parents against vaccination in preadolescent was higher in the >45 years old (29.4%); however, most of them appeared favorable to the information campaigns regarding the vaccine (P value <0.001). Our study showed that mothers of unvaccinated preadolescent girls have suboptimal knowledge on the topic. Moreover, the implementation of communication strategies dedicated to the population segment appears as a central aspect. As HPV vaccination keeps being a public health concern, it is fundamental to understand which trigger should be managed by healthcare decision makers to boost the vaccination campaigns.

Prediction model for residual high-grade cervical intraepithelial lesions

The aim of the study was to evaluate risk factors associated with high-grade cervical intraepithelial lesions (HSIL) in patients undergoing a second cervical excision procedure due to positive surgical margins and to create a prediction model for residual disease. This study included patients with HSIL positive surgical margins following loop electrosurgical excision procedures (LEEP) between March 2015 and August 2019. HSIL in the second cervical excision pathology in these patients was accepted as residual disease. For residual disease prediction, a multivariate logistic regression and stepwise elimination analysis of 14 variables including demographic characteristics, clinical characteristics, pathology results and HPV genotypes of the patients was performed. Second cervical excision procedures were performed in 290 patients 85(29.4%) of these patients had CIN 2 (cervical intraepithelial neoplasia) and 205 (70.6%) had CIN 3. In the second excision procedure, 166 patients (57.2%) had ≤CIN 1, 124 patients (42.8%) had ≥CIN2. The prediction model of residual disease includes only 3 variables out of the 14 different clinical characteristics (AUC=0.605 [0.539-0.671]). These variables are gravida (adjusted OR: 1.15 [0.97-1.38], P=0.107), CIN2-3 presence in the endocervical canal in the first LEEP specimen (adjusted OR: 1.52 [0.94-2.47], P=0.091) and the presence of HR-HPV except 16/18 lesions (adjusted OR: 0.64 [0.38-1.06], P=0.083). A prediction model was designed with our data, from variables reported to be risk factors for residual disease in previous studies. While this model was statistically significant, it was poor at distinguishing residual disease. A prediction model can be designed to guide clinicians with future studies.

Association of high expression of CD44 in clinicopathological factors of endometrial cancer

Clinical stages, histologic type, degree of cell differentiation, myometrial invasion, and lymph-vascular space invasion (LVSI) have been identified as clinicopathological factors that are predictive for endometrial cancer, however, further prognostic indicators are still required to account for the heterogeneity of this cancer. Adhesion molecule CD44, affects the invasion, metastasis, and prognosis of many forms of cancer. The purpose of this study is to examine the expression of CD44 in endometrial cancer and its correlation with established prognostic variables. A cross-sectional study was conducted on 64 samples of endometrial cancer from Wahidin Sudirohusodo Hospital and Hasanuddin University Hospital. Immunohistochemical analysis was used to detect CD44 expression using mouse anti-human CD44 monoclonal antibody. Differences in Histoscore were studied to determine the association between CD44 expression and clinicopathological factors of endometrial cancer. Of the overall sample, 46 samples were in the early stage, whereas 18 samples were in the advanced stage. High expression of CD44 was associated with advanced stage compare than early stage (P=0.010), poor differentiation compare than well-moderate differentiation (P=0.001), myometrial invasion ≥50% compare than myometrial invasion <50% (P=0.004), and positive LVSI compare than negative LVSI (P=0.043) in endometrial cancer, but not associated with histological type of endometrial cancer (P=0.178). High expression of CD44 may be considered as a poor prognostic marker and predictive marker for targeted therapy in endometrial cancer.

Clinical factors predicting objective response to bevacizumab-based chemotherapies in advanced and recurrent epithelial ovarian cancer

Bevacizumab-based chemotherapies are commonly administered in the treatment of patients diagnosed with epithelial ovarian cancer (EOC). The primary aim of this study was to assess the factors that predict the objective response to bevacizumab-based therapies in cases of advanced and recurrent EOC. The retrospective data of 264 patients with EOC from the current study were collected between 2009 and 2022 at our clinic. Survival analyses were conducted utilizing the Kaplan-Meier method and the log-rank test. Binary logistic regression analysis was employed to assess the factors predicting the objective response. A predominant subset of patients (83%) presented with serous adenocarcinoma, exhibiting a high-grade differentiation at 87%. The vast majority (80%) of the cohort experienced disease recurrence. Three-fourths of the cases received bevacizumab in combination with platinum-based doublet chemotherapy. In the multivariate analysis, clinical factors such as a disease recurrence (P=0.031), upfront tumor debulking surgery before bevacizumab (P=0.009), doublet chemotherapy (P=0.003), and the presence of malignant pleural effusion (P=0.024) emerged as significant determinants influencing the Objective Response Rate (ORR) in patients undergoing bevacizumab-based therapy. The ORR was 67.5% (N.=178), comprising 15.2% complete responses (N.=40) and 52.1% partial responses (N.=138). The median Progression-Free Survival (PFS) and Overall Survival (OS) were estimated at 10.2 months (95% CI, 8.60-11.9) and 20.1 months (95% CI, 16.0-24.2), respectively. The responses to bevacizumab-based chemotherapies could be predict by the presence of malignant pleural effusion, disease recurrence, upfront tumor debulking surgery and doublet regimen of chemotherapy.

Adjuvant radiotherapy for early-stage endometrial cancer based on randomized controlled trials: a narrative review

Endometrial carcinoma (EC) is the most common gynecologic malignancy in the USA, with surgical staging as the cornerstone of treatment. Although most patients are diagnosed at an early stage, adjuvant therapies, including external beam radiation therapy (EBRT), vaginal brachytherapy (VBT), and systemic treatments, are employed in select cases to reduce recurrence risk. This review highlights data from randomized controlled trials assessing the efficacy of adjuvant radiotherapy in early-stage EC. For low-risk EC, studies suggest that postoperative brachytherapy has minimal impact on locoregional recurrence and is not recommended without significant uterine risk factors. In intermediate-risk EC, trials such as GOG 99 and PORTEC-1 demonstrated reduced recurrence with pelvic RT, particularly in high-intermediate risk subsets, though overall survival benefits were not observed. For high-intermediate risk EC, PORTEC-2 showed that VBT effectively controls vaginal recurrence with less morbidity compared to EBRT, recommending VBT as the preferred modality. Medium-risk cases benefit similarly from VBT alone, as shown in Swedish trials. In high-risk EC, RCTs such as GOG 249 and PORTEC-3 examined the addition of chemotherapy to radiotherapy, finding comparable recurrence and survival outcomes between VBT with chemotherapy and EBRT, though acute toxicity was higher with combined therapy. Across these trials, the degree of lymphovascular space invasion (LVSI), patient age, tumor grade, and histology were key prognostic factors influencing treatment recommendations. Despite advancements in molecular classification and modern radiotherapy techniques, most data derive from earlier studies, emphasizing the need for updated research to refine treatment paradigms.

Barbed suture in laparoscopic myomectomy

Uterine myomas are the most common benign gynecological tumors among women of reproductive age. The laparoscopic approach, when feasible, is considered the most suitable and safe technique for intervention. Typically, uterine muscular wall defects are sutured with absorbable filaments. However, performing intra-corporeal knots during laparoscopic procedures demands significant surgical abilities and experience. While laparoscopic myomectomies are often recommended, they pose a high risk of hemorrhage. Barbed sutures may address the challenges of laparoscopic knotting due to their inherent barbs, leading to filament cohesion with tissues. This characteristic could potentially reduce the total operative time and blood loss during surgery. In consideration of the latest literature meta-analysis on the topic, published in 2018 and cited in the present work, six papers were included in this review, excluding case reports, reviews and articles without a control group. The objective of this narrative review is to explore the literature and establish the safety profile of barbed suture compared to conventional laparoscopic sutures. Additionally, given the potential for postoperative adhesion formation with the use of barbed sutures, the review also emphasizes reproductive outcomes. Consistent with previous literature, patients undergoing barbed suture laparoscopic myomectomy experienced significantly lower suturing time and blood loss. Regarding obstetric outcomes, all studies analyzing this aspect concluded that barbed sutures in myomectomy are as safe as, and represent an easier alternative to, conventional sutures. Importantly, these findings did not adversely affect pregnancy outcomes.

Tailoring parametrectomy for early cervical cancer (Stage IA-IIA FIGO): a review on surgical, oncologic outcome and sexual function

Cervical cancer is currently one of the most common cancers afflicting the female population worldwide and in industrialized countries the presence of screening and a specific diagnostic and therapeutic process has favored early diagnosis of cervical cancer. In literature have found that reducing the radicality on the parametria in early cervical cancer (ECC), reduces complications without impacting oncological outcomes, but the data in the literature are not yet clear. Searching on PubMed, we included 1473 articles from January 1974 to 2020. We identified all the studies that compared different type of radical hysterectomy in the primary surgical treatment of ECC. 16 articles were elected for the review. Modified radical hysterectomy (Piver II/Querleu-Morrow Type B) in ECC, if compared to CRH (Piver III/Querleu-Morrow Type C2), is not associated with worse cancer outcome and patient survival, but it is associated with a minor operating time, lower blood loss and minor bladder dysfunction. Nerve sparing radical hysterectomy approach (NSRH/Querleu-Morrow Type C1) compared to CRH (Piver III/Type C2) in the ECC, with our data we can confirm a non-inferiority regarding the oncological outcome. Reduced radicality on the parametrium offers positive effects on the quality of life (sexual life and bladder function) of patients without impacting on survival, oncological outcome.

Relationship between cervical excisional treatment for cervical intraepithelial neoplasia and obstetrical outcome

The aim of our systematic review was the assessment of effects of excisional treatments for the management of cervical intraepithelial neoplasia (CIN) on preterm delivery (PD), lower birth weight (LBW), preterm premature rupture of membrane (PPROM) and obstetrical outcomes. A structured search was carried out in PubMed-Medline, Embase, and Cochrane Controlled Trials Register databases through November 30, 2019. The search included a combination of the following terms: "loop electrosurgical excision procedure (LEEP)," "large loop excision of transformation zone (LLETZ)," "cold-knife conization (CKC)," "laser cervical conization (CLC)," "preterm delivery" and "neonatal outcome." Thirty-two of 561 publications considered were included: 28 retrospective series, 2 prospective studies and 2 multicenter trials. Globally in several studies there was a significant increase in PD, measured by the relative risk, in the women underwent a surgical procedure for the CIN. In their majority, the studies were retrospective and therefore a high risk of bias. This systematic review shows that the surgical treatment of the CIN was associated with an increased risk of PD, LBW and pPROM before 37 pregnancy weeks compared to untreated women, especially in a CKC and LLETZ procedure. Moreover, the increase of the of PD was associated with cone size, cervical length, repeated treatment and a short conization-to-pregnancy interval.

Cancer screenings among sexual and gender minorities by midwives' point of view

Although women belonging to sexual and gender minorities are more at risk of gynecological and breast cancer, pieces of evidence have been provided that this population finds hardships getting involved in cancer screening programs. This happens because they tend to avoid clinical settings because of fear of discrimination, heteronormative assumptions, heterosexism, classism, and homophobic slurs by healthcare professionals. On the other hand, medical programs that allow healthcare providers to have experience with LGBTQ people are scarce and there are no specific tools to assess sexual cancer risks in this population. Studies included were obtained searching MEDLINE with keywords "lesbians," "queer women," "trans women," "LGBTQ women," "cervical cancer screening," "pap test," "oncology screening," "mammogram" and "prevention." Furthermore, 1577 papers were found. After filtering for species, sex, language, and time range, 820 papers were left. The number of works included was 24 after title screening and 20 after abstract screening and full-text screening. More research will be needed to develop tools with an inclusive, non-judgmental, and open language capable of engaging the LGBTQ community. Cancer screening programs involve a large variety of healthcare providers including midwives. Midwives are multifaceted healthcare professionals whose large competence spectrum includes a variety of knowledge and skills going from antenatal care to education and research and they may efficiently provide cancer screenings. Midwives have been asking for more specialistic roles and calling for specific instruction to face the complex and ever-changing reality.

Reducing the radicality of surgery for vulvar cancer: are smaller margins safer?

Vulvar cancer accounts for ~4% of all gynecological malignancies and the majority of tumors (>90%) are squamous cell (keratinizing, ~60% and warty/basaloid, ~30%). Surgical excision forms the foundation of treatment, with resection margin status being the single most influential factor when predicting clinical outcome. There has been a paradigm shift concerning surgical approaches and radicality when managing vulvar cancer within recent times, largely owing to a desire to preserve vulvar structure and function without compromising oncological outcome. As such the safety of the size of resection margin has been called into question. In this narrative review we consider the current literature on the safety of resection margins for vulvar cancer. PubMed, Medline and the Cochrane Database were searched for original peer-reviewed primary and review articles, from January 2005 to January 2020. The following search terms were used vulvar cancer surgery, vulvar squamous cell carcinoma, excision margins, adjuvant radiation. A pathological tumor margin of <8 mm has been widely considered to indicate "close" margins. This measurement after fixation of the tumor is considered comparable to a surgical resection margin of around 1cm, following an estimated 20% tissue shrinkage after formalin fixation and a 1-2cm clinical surgical margin in order to achieve the 8 mm final pathological margin. A surgical resection margin of 2-3mm does not appear to be associated with a higher rate of local recurrence than the widely used limit of 8 mm. As such the traditional practice of re-excision or adjuvant radiotherapy based on "close" surgical margins alone needs to be closely evaluated, since the attendant morbidity associated with these procedures may not be outweighed by oncological benefit.

Gynecologic oncology top-cited articles: an international analysis

The aim of this paper was to study the top-cited per year (CPY) original articles published in the leading subspecialty journals in gynecologic oncology and in the leading general obstetrics and gynecology journals. We used the Web of Science and iCite databases to mine the original articles and review articles in the field of gynecologic oncology in the following journals: Gynecologic Oncology, The International Journal of Gynecological Cancer, The American Journal of Obstetrics and Gynecology and the Obstetrics & Gynecology. Top CPY articles from the four journals were analyzed and compared in a two-time point analysis. A total of 23,252 original articles and reviews were identified. The 100 Top-CPY articles were published from 1983 to 2021. Seventy (70%) in Gynecologic Oncology journal, 20 (20%) in The International Journal of Gynecological Cancer, eight (8%) in Obstetrics & Gynecology and two (2%) in The American Journal of Obstetrics and Gynecology. The most common study methodology was observational studies (20%), followed by guidelines/consensus papers (19%). The most common study topic was ovarian cancer (41%). North America originating authors composed 62% of the top CPY publications, followed by Europe (21%). The most common country of authorship was the United States (52%) followed by Canada (10%). CPY were similar in the publications before vs. after 2014 (P=.19). Study designs, study topics and continent of authorship were similar in both periods. The proportion of multi-center studies was higher after 2014 (66.6% vs. 28.8%, P=0.002) and the proportion of open access publications was higher after 2014 (66.6% vs. 15.4%, P<.001). Funded studies were more common after 2014 (75.0% vs. 53.8%, P=0.028). Ovarian cancer is the top CPY area of research in gynecologic oncology. This field is leaded by authors from the United States with multi-center studies proportion increasing in recent years. It is important to promote further high-quality research in other countries to disseminate knowledge and equality.

Office endometrial sampling: effectiveness and predictive factors of success in Novak versus Endosampler devices

The study aimed to evaluate the rate of endometrial sampling (ES) failure, predictive factors of success, and reliability as diagnostic methods of Endosampler versus Novak. A retrospective single-center study was carried out with all patients who underwent ES via Endosampler or Novak in 2020 and 2021. Demographic data, personal background, and histopathologic results were evaluated. Eighty-six patients underwent ES by Novak and 90 by Endosampler. The failure rate of ES was 43.2% with lower values for Endosampler (33.3% vs. 53.5%, P<0.05). Age, biopsy device, menopausal status, indication for biopsy, and amount of sample collected were predictive factors of failure. Analyzing each device, Endosampler was only affected by menopausal status. Only 50% in Novak and 62.5% in the Endosampler group of endometrial neoplasia cases were detected by these methods. Analyzing the performance for endometrial neoplasia (EN), we obtained higher values of sensitivity and accuracy for Endosampler (62.5% vs. 50.0% and 83.3% vs. 72.7%), respectively. In our study, the failure rate obtained was in line with other previous studies. Menopausal status, age, type of biopsy device, indication for biopsy, and amount of sample collected affected ES performance. Analyzing diagnostic performance for EN, we found that these methods have better reliability for positive results than for negative ones, which may indicate the need for further evaluation in cases of high clinical suspicion. In short, we obtain a higher rate of success rate in Endosampler devices and better performance in diagnosing EN, which is the major objective of an ES.

Unilateral hydroureteronephrosis after introduction of a levonorgestrel-releasing intrauterine system: a case report and literature review

Insertion of a LNG-Intra-uterine System (LNG-IUS) has many gynecological indications. The approved indications worldwide are contraception, treatment of abnormal uterine bleeding depending on not organic disease, and endometrial protection in case of an estrogenic therapy. Instead adenomyosis, fibroids, and fertility-sparing management of endometrial hyperplasia or early endometrial cancer in patients with desire of pregnancy are off label indications. Hydroureteronephrosis is an uncommon complication during LNG-IUS insertion. There are few cases described in the literature. The first diagnostic approach for this complication is an abdominal-pelvic ultrasound scan to identify the abnormal position of the device. Diagnostic management includes computed tomography (CT) or magnetic resonance imaging (MRI), which are necessary to confirm hydroureteronephrosis and to assess the exact location of the LNG-IUS in the abdomen. A minimally invasive approach is the standard of care with the removal of the device, while the therapeutic management of the hydroureteronephrosis depends on ureteral and kidney involvement. We report the history of a dislocated LNG-IUS in the left paracervical space with subsequent ipsilateral hydroureteronephrosis. In our case we removed the device through hysteroscopy and later inserted a J-J stent. Follow-up at three months revealed the persistence of left hydroureteronephrosis, so we performed ureter reimplantation. We also performed a review of the literature to analyze common diagnostic and therapeutic pathways for this rare complication.

Should laparoscopy be revisited in the management of stage II endometrial cancer in the post-LACC era?

A recent randomized trial showed that laparoscopy had poorer outcomes compared with open surgery for early-stage cervical cancer. Whether this is of concern in endometrial cancer, when the cervix is involved has received little attention. This study aimed to investigate whether there is any difference on overall and cancer specific survival between patients treated with laparoscopy and laparotomy for stage II endometrial cancer. Data from patients with histologically proven stage II endometrial cancer who were treated between 2010 and 2019 in a single cancer center were reviewed. Demographic, histopathological characteristics and treatment modalities were recorded. Recurrence rate, cancer specific and overall survival were compared between patients that were treated with laparoscopic and open surgery. From 47 patients with stage II disease, 33 (70%) were treated with laparoscopy and 14 (30%) with open surgery. There was no difference on age (P=0.86), BMI (P=0.76), Comorbidity Index Score (P=0.96), upstaging/upgrading after surgery (P=0.41), performance of lymphadenectomy (P=0.74), histological type (P=0.32), LVSI (P=0.15), depth of myometrial invasion (P=0.07), postoperative hospital stay (P=0.18) and administration of adjuvant treatment (P=0.11) between the two groups. Recurrence rate (P=0.756), overall (P=0.606) and cancer specific survival (P=0.564) were also comparable between laparoscopy and laparotomy groups. Laparoscopic and open surgery seem to have comparable outcomes for stage II endometrial cancer. The oncological safety of laparoscopy for stage II endometrial cancer should be further investigated with a randomized controlled trial.

Publisher

Edizioni Minerva Medica

ISSN

2724-606X