Valentina Chiappa

Abdominal specimen retrieval in endometrial cancer patients with large uteri

Objective: Endometrial cancer surgery has a low risk of specimen fragmentation, but removing large uteri can be challenging. This study aimed to assess whether the use of minilaparotomic incision for specimen retrieval compromises the benefits of minimally invasive surgery in endometrial cancer patients with a large uterus or utero-vaginal discrepancy. Methods: This is a retrospective multi-institutional study, including endometrial cancer patients with FIGO 2009 clinical stage I–II, undergoing minimally invasive staging surgery (laparoscopic or robot-assisted) followed by minilaparotomic specimen retrieval. A propensity-matched algorithm was used to compare outcomes of minimally invasive staging with open surgery. Results: The study included 45 propensity-matched pairs (90 patients): 45 underwent minimally invasive staging with minilaparotomic specimen retrieval and 45 underwent open staging. Patients undergoing minimally invasive surgery plus trans-abdominal specimen retrieval experienced longer median operative time (95 vs. 85 minutes; p=0.0017), lower blood loss (50 vs. 100 ml; p<0.001), and shorter length of hospital stay (3 vs. 5 days; p<0.001) in comparison to patients undergoing open surgery. No intraoperative complication occurred. No intraoperative transfusions were administered in both cohorts. No statistically significant differences in complications rates were registered between groups (p=0.266). No differences in term of disease-free (p=0.833, log-rank test) and overall (p=0.723, log-rank test) survival was noted between groups. Conclusions: Transabdominal specimen retrieval does not reduce the benefits of minimally invasive staging in endometrial cancer with large uteri or utero-vaginal disproportion. Uterine size is not a limitation for minimally invasive surgery. Further studies are needed to confirm these results and define the optimal approach.

Expectant management or conization for persistent low-grade cervical intraepithelial neoplasia: Analysis of 5-year outcomes

Objective: To investigate to describe outcomes of conization or expectant management for women with persistent (>24 months) low-grade cervical intra-epithelial neoplasia. Methods: This is a retrospective analysis focusing on five-year outcomes after persistent, histologically confirmed, low-grade cervical intra-epithelial neoplasia undergoing conization or expectant management. Results: Charts of 219 women with persistent low-grade cervical lesions were retrieved. Overall, 98 (44.7%) and 121 (55.3%) women had conization and observation, respectively. Patients receiving conization were older than patients having observation (43 (range, 24-77) vs. 39 (range, 25-68) years; p=0.013). Focusing on the group of patients receiving conization, 16 (16.3%) women were diagnosed with CIN2+. The five-year risk of secondary conization was 5% (n=5). Focusing on patients having observation (n=121), 18 (14.8%) patients received conization, after a median of 16.5 (range, 6-30) months. Seven (5.8%) and 11 (9.1%) patients were diagnosed with persistent CIN1 and CIN2+, respectively. Not fully visible squamous-columnar junction at colposcopic examination (p=0.035) was associated with CIN2+ occurrence. No invasive cancer was observed Conclusions: Conization for persistent low-grade cervical intra-epithelial neoplasia revealed “occult” CIN2+ in 16% of patients. However, expectant management appears safe and effective in this context, in women with fully visible squamous columnar junction. The decision between conization and expectant management should be discussed on an individual basis.

Malignant germ cells tumor of the ovary

Malignant ovarian germ cell tumors are rare and diverse malignancies, accounting for approximately 5% of all ovarian cancers. Primarily affecting young women, these tumors present unique challenges, particularly in balancing effective treatment with fertility preservation. Early diagnosis is common due to the rapid tumor growth and symptoms such as abdominal pain and distension, leading to favorable prognoses when combined with the high chemosensitivity of platinum-based regimens. Fertility-sparing surgery is the cornerstone of treatment for stage I disease, often followed by close surveillance to minimize the long-term toxicities of chemotherapy. Pathology is pivotal for diagnosis, incorporating immunohistochemical markers to differentiate malignant ovarian germ cell tumors subtypes, including dysgerminomas, yolk sac tumors, and immature teratomas. Advanced imaging modalities like ultrasound, magnetic resonance imaging, and computed tomography are essential for staging, monitoring treatment response, and detecting recurrences. Despite high cure rates, long-term follow-up is crucial to manage late toxicities, such as gonadal dysfunction and secondary malignancies. Recurrent malignant ovarian germ cell tumors present significant therapeutic challenges. High-dose chemotherapy with stem-cell transplantation offers promise in select cases, while the role of secondary cytoreductive surgery and radiotherapy is limited to specific indications. Emerging targeted therapies and novel approaches, such as KIT inhibitors for dysgerminomas with KIT mutations, remain experimental, with limited success reported so far. The rarity and heterogeneity of malignant ovarian germ cell tumors impede large-scale research efforts, underscoring the need for greater understanding of their molecular and genetic landscape to develop more effective and personalized therapies.

Ultrasound examiners' ability to describe ovarian cancer spread using preacquired ultrasound videoclips from a selected patient sample with high prevalence of cancer spread

ABSTRACTObjectivesTo assess the ability, as well as factors affecting the ability, of ultrasound examiners with different levels of ultrasound experience to detect correctly infiltration of ovarian cancer in predefined anatomical locations, and to evaluate the inter‐rater agreement regarding the presence or absence of cancer infiltration, using preacquired ultrasound videoclips obtained in a selected patient sample with a high prevalence of cancer spread.MethodsThis study forms part of the Imaging Study in Advanced ovArian Cancer multicenter observational study (NCT03808792). Ultrasound videoclips showing assessment of infiltration of ovarian cancer were obtained by the principal investigator (an ultrasound expert, who did not participate in rating) at 19 predefined anatomical sites in the abdomen and pelvis, including five sites that, if infiltrated, would indicate tumor non‐resectability. For each site, there were 10 videoclips showing cancer infiltration and 10 showing no cancer infiltration. The reference standard was either findings at surgery with histological confirmation or response to chemotherapy. For statistical analysis, the 19 sites were grouped into four anatomical regions: pelvis, middle abdomen, upper abdomen and lymph nodes. The videoclips were assessed by raters comprising both senior gynecologists (mainly self‐trained expert ultrasound examiners who perform preoperative ultrasound assessment of ovarian cancer spread almost daily) and gynecologists who had undergone a minimum of 6 months' supervised training in the preoperative ultrasound assessment of ovarian cancer spread in a gynecological oncology center. The raters were classified as highly experienced or less experienced based on annual individual caseload and the number of years that they had been performing ultrasound evaluation of ovarian cancer spread. Raters were aware that for each site there would be 10 videoclips with and 10 without cancer infiltration. Each rater independently classified every videoclip as showing or not showing cancer infiltration and rated the image quality (on a scale from 0 to 10) and their diagnostic confidence (on a scale from 0 to 10). A generalized linear mixed model with random effects was used to estimate which factors (including level of experience, image quality, diagnostic confidence and anatomical region) affected the likelihood of a correct classification of cancer infiltration. We assessed the observed percentage of videoclips classified correctly, the expected percentage of videoclips classified correctly based on the generalized linear mixed model and inter‐rater agreement (reliability) in classifying anatomical sites as being infiltrated by cancer.ResultsTwenty‐five raters participated in the study, of whom 13 were highly experienced and 12 were less experienced. The observed percentage of correct classification of cancer infiltration ranged from 70% to 100% depending on rater and anatomical site, and the median percentage of correct classification for the 25 raters ranged from 90% to 100%. The probability of correct classification of all 380 videoclips ranged from 0.956 to 0.975 and was not affected by the rater's level of ultrasound experience. The likelihood of correct classification increased with increased image quality and diagnostic confidence and was affected by anatomical region. It was highest for sites in the pelvis, second highest for those in the middle abdomen, third highest for lymph nodes and lowest for sites in the upper abdomen. The inter‐rater agreement of all 25 raters regarding the presence of cancer infiltration ranged from substantial (Fleiss kappa, 0.68 (95% CI, 0.66–0.71)) to very good (Fleiss kappa, 0.99 (95% CI, 0.97–1.00)) depending on the anatomical site. It was lowest for sites in the upper abdomen (Fleiss kappa, 0.68 (95% CI, 0.66–0.71) to 0.97 (95% CI, 0.94–0.99)) and highest for sites in the pelvis (Fleiss kappa, 0.94 (95% CI, 0.92–0.97) to 0.99 (95% CI, 0.97–1.00)).ConclusionsUltrasound examiners with different levels of ultrasound experience can classify correctly predefined anatomical sites as being infiltrated or not infiltrated by ovarian cancer based on video recordings obtained by an experienced ultrasound examiner, and the inter‐rater agreement is substantial. The likelihood of correct classification as well as the inter‐rater agreement is highest for sites in the pelvis and lowest for sites in the upper abdomen. However, owing to the study design, our results regarding diagnostic accuracy and inter‐rater agreement are likely to be overoptimistic. © 2025 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Age-specific predictors of cervical dysplasia recurrence after primary conization: analysis of 3,212 women

This study aimed to identify predictors of recurrence/persistence of cervical intraepithelial neoplasia grade 2+ (CIN2+) lesion (r-CIN2+) after primary conization. Retrospective analysis involving all consecutive women having conization for CIN2+ between 1998 and 2018. The risk of r-CIN2+ was assessed using Kaplan-Meier and Cox models. Data of 3,212 women were retrospectively identified. After a mean follow-up of 47 (±22.2) months, 112 (3.5%) patients developed r-CIN2+. Mean time interval between prior conization and diagnosis of r-CIN2+ was 26.2 (±13.2) months. Via multivariate analysis, presence of high-risk human papillomavirus (HPV) types at the time of CIN2+ diagnosis, hazard ratio (HR)=3.40 (95% confidence interval [CI]=1.66-6.95) for HPV16/18 and HR=2.59 (95% CI=1.21-5.55) for HPV types other than 16/18, positive margins at primary conization, HR=4.11 (95% CI=2.04-8.26) and HPV persistence after conization, HR=16.69 (95% CI=8.20-33.9), correlated with r-CIN2+, independently. Considering age-specific HPV types distribution, we observed that HPV16/18 infection correlated to an increased risk of r-CIN2+ only in young women (aged ≤25 years; p=0.031, log-rank test); while in the older population (>25 years) HPV type(s) involved had not impact on r-CIN2+ risk (p>0.200, log-rank test). HPV persistence is the main factor predicting r-CIN2+. Infection from HPV16/18 has a detrimental effect in young women, thus highlighting the need of implementing vaccination against HPV in this population. Further prospective studies are warranted for tailoring clinical decision-making for post-conization follow-up on the basis of risk factors.

BYL719 (alpelisib) for the treatment of PIK3CA-mutated, recurrent/advanced cervical cancer

Purpose: Advanced/recurrent cervical cancer has limited therapeutic options, with a median progression-free survival after the failure of systemic treatments ranging between 3.5 and 4.5 months. Here, we reported our preliminary experience in the use of BYL719 (alpelisib) in advanced/recurrent cervical cancer after failure of at least 2 lines of treatment. The Istituto Nazionale dei Tumori di Milano approved this investigation. Methods: From April 2020 to September 2020, 17 consecutive patients with recurrent cervical cancer had Next Generation Sequencing (NGS). Of these, six patients harboring the PIK3CA mutation were included in the study. All patients had been treated with at least 2 previous lines of systemic treatment: 3 patients received >2 prior lines of treatment in the recurrent or metastatic setting; 60% had received prior bevacizumab in combination with chemotherapy. All patients started alpelisib at the daily dosage of 300 mg. Results: Investigator-assessed confirmed objective response rate (ORR) was 33%. The disease control rate (DCR) was 100%. According to RECIST 1.1, two patients had a partial response (PR), and four patients had stable disease (SD). No complete response was observed. The mean duration of response (DOR) was 11.5 (SD 3.75) months; five patients had PR lasting for >9 months. One patient stopped the treatment at 0.82 months due to the onset of a grade 2 adverse event (AE) (skin rash). Grade 3 treatment-related AEs included: lymphoedema (n = 1, 17%) and rash (n = 1, 17%). No treatment-related grade 4-5 AEs occurred. Conclusions: Our preliminary data highlighted a high level of efficacy in this setting of patients. Further trials are needed to assess the safety and effectiveness of alpelisib in PIK3CA-mutated recurrent/advanced cervical cancer.

Comparison of ultrasound with computed tomography and whole‐body diffusion‐weighted MRI in prediction of surgical outcome using ESMO ‐ ESGO criteria in patients with tubo‐ovarian carcinoma: prospective ISAAC study

ABSTRACT Objective To test the non‐inferiority of extended abdominopelvic ultrasound examination compared with contrast‐enhanced computed tomography (CT) and whole‐body diffusion‐weighted magnetic resonance imaging (WB‐DWI/MRI) in discriminating preoperatively between resectable and non‐resectable disease based on the European Society for Medical Oncology (ESMO) and European Society of Gynecological Oncology (ESGO)‐defined criteria in patients with tubo‐ovarian carcinoma. Methods The Imaging Study on Advanced ovArian Cancer was a prospective multicenter observational study conducted in five European gynecological oncology centers. All centers had ESGO accreditation to perform advanced ovarian cancer surgery, and ultrasound examinations were performed by a European Federation of Societies for Ultrasound in Medicine and Biology level‐III examiner in a standardized manner. Included in the analysis were patients enrolled between 2020 and 2022 with suspected or histologically proven primary tubo‐ovarian (including peritoneal) carcinoma who, for the purposes of the study, underwent ultrasound and CT imaging, as well as WB‐DWI/MRI if available, prior to surgery. The index tests, which included the preoperative imaging modalities as well as intraoperative exploration at the start of surgery, supplemented by biopsy or follow‐up imaging for extra‐abdominal locations, evaluated the presence of disease at eight anatomical sites that, if infiltrated, would indicate non‐resectability of the tumor according to the ESMO‐ESGO criteria. Surgical outcome, described by the surgeons at the end of the procedure, was used as the reference standard and non‐resectability was defined as the presence of residual disease > 1 cm or when debulking surgery was not feasible. The area under the receiver‐operating‐characteristics curve (AUC) and F 1  score were used to assess the performance of the preoperative imaging methods and surgical exploration in discriminating between patients with resectable and those with non‐resectable disease, based on the ESMO‐ESGO criteria. We also calculated the percentage agreement between imaging findings and surgical exploration findings at the start of surgery, supplemented when applicable by biopsy or follow‐up imaging for extra‐abdominal locations, regarding the presence of tumor infiltration at each of the eight anatomical sites associated with non‐resectability. Results Of 279 patients enrolled during the study period, 242 were included in the final analysis. In the subgroup of 167 patients who underwent surgery and had been examined by all three imaging methods, the AUC of the three imaging modalities and surgical exploration for discriminating between resectable and non‐resectable disease based on the ESMO‐ESGO criteria was 0.835 (95% CI, 0.756–0.915) for ultrasound, for CT it was 0.754 (95% CI, 0.664–0.843), for WB‐DWI/MRI it was 0.720 (95% CI, 0.626–0.814) and for surgical exploration it was 0.952 (95% CI, 0.915–0.988). Ultrasound was not inferior to CT or WB‐DWI/MRI, based on the AUC and F 1 score, in discriminating between patients with resectable and those with non‐resectable tubo‐ovarian carcinoma. At surgical exploration, at least one non‐resectability criterion was present in 32.2% cases. The criteria observed most frequently at surgical exploration were small‐bowel involvement (23.6% of cases), diffuse deep infiltration of the root of the small‐bowel mesentery (18.2% of cases) and hepatic hilum involvement (5.4% of cases). The percentage agreement between ultrasound and surgical exploration in assessing the presence of disease in at least one of the eight anatomical sites that, if infiltrated, would indicate non‐resectability of tumor, was 83.9%, surpassing the percentage agreement with surgical exploration of both CT (77.7%) and WB‐DWI/MRI (75.8%). Conclusion When performed by an experienced examiner, ultrasound is not inferior to either CT or WB‐DWI/MRI in discriminating between resectable and non‐resectable disease in patients with tubo‐ovarian carcinoma, based on evaluation of the presence of the disease in at least one of eight anatomical sites that, if infiltrated, would indicate non‐resectability of the tumor. © 2025 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Imaging Study in Advanced Ovarian Cancer

The aim of the study is the assessment of tumour sites critical for the achievement of optimal cytoreduction in patients with advanced ovarian cancer using Ultrasound, CT and WB-DWI/MRI. The study uses an equivalence design with a hypothesis that cases with non-resectable disease identified by Index test (Ultrasound, CT and WB-DWI MRI) are equivalent to a portion of cases identified during surgery.