Jurgen M. J. Piek

Evaluating Performance of a Deep Learning–based Artificial Intelligence Model for Ovarian Tumor Classification Using a Multicenter CT Dataset

A computer-aided diagnosis model for preoperative classification of ovarian tumors, developed using a multicenter CT dataset, demonstrated comparable performance to US-based models and radiologists on the internal and external test sets, illustrating challenges due to the heterogeneous nature of the disease and multicenter data.

Pathogenesis of peritoneal high‐grade serous carcinoma after risk‐reducing surgery: a systematic review

AbstractGermline BRCA1/2 pathogenic variant carriers have an increased risk for high‐grade serous carcinoma (HGSC) and are therefore advised to have risk‐reducing salpingo‐oophorectomy around the age of 40. However, a risk of 0.9% to develop peritoneal HGSC remains in these women, which increases to 27.5% when serous tubal intraepithelial carcinoma (STIC) is detected. The pathophysiological mechanism that leads to the development of peritoneal HGSC after salpingectomy or salpingo‐oophorectomy is still largely unknown. In this systematic review, we aim to provide insights into the pathogenic pathways of peritoneal HGSC after salpingectomy or salpingo‐oophorectomy. Therefore, we performed a systematic search for studies investigating pathophysiological mechanisms related to peritoneal HGSC in PubMed and EMBASE. A total of 49 articles were included in this study. Most evidence was found on mechanisms following a tubal origin, such as clonality between STIC and peritoneal HGSC as well as molecular similarities between fallopian tube (FT) epithelium and peritoneal HGSC. Additionally, FT epithelium was shown to adhere to the ovary and could therefore stay present after isolated salpingectomy. There might be a role for the endometrium, as it was observed that serous endometrial intraepithelial carcinoma (SEIC) has a clonal relationship with extra‐uterine HGSC. The role of the ovary seems limited, although some mouse models show a role for follicular fluid in the dissemination of malignant cells on the peritoneum. In conclusion, different mechanisms might be responsible for peritoneal HGSC development after bilateral salpingectomy or salpingo‐oophorectomy. Most available evidence supports the dissemination of precursor cells originating in the FT. Also, a possible role for the endometrium was found. An ovarian origin seems less likely; however, execution of oophorectomy does not seem obsolete in clinical practice as follicular fluid might promote dissemination and residual tubal tissue can be present on the ovary after salpingectomy.

Response to Systemic Therapies in Patient-Derived Cell Lines from Primary and Recurrent Adult Granulosa Cell Tumors

Abstract In patients with the rare adult-type granulosa cell tumor (aGCT), surgery is the primary treatment for both primary and recurrent disease. In cases of inoperable disease, systematic therapy is administered, but variable response rates and drug resistance complicate predicting the most effective therapy. Drug screen testing on patient-derived cell lines may offer a solution. In a national prospective study on aGCT, fresh tissue was cultured into 2D cell lines, testing 27 clinical and experimental drugs. Dose–response curves and synergy were calculated using GraphPad Prism and CompuSyn software. We established 34 patient-derived cell lines from tissue of 20 patients with aGCT. Of these, seven patients had a primary diagnosis of aGCT and 13 patients had recurrent disease. In eight patients, multiple tumor locations were cultured. On each cell line, 10 monotherapies and 17 combinations of drugs were tested. Carboplatin/gemcitabine showed efficacy and synergy in almost all patient-derived cell lines. Synergy could not be detected in the regular carboplatin/paclitaxel and carboplatin/etoposide combinations. Experimental combinations alpelisib/fulvestrant and alpelisib/gemcitabine showed efficacy of more than 75%. Drug screens on patient-derived tumor cell lines reflect the reality of the variable response of systemic therapy in patients with aGCT. In future research, this technique may be used to personalize the systemic treatment of patients with aGCT in a clinical study. The good response to carboplatin/gemcitabine in our patient-derived cell lines can then be confirmed in a clinical setting.

Endoscopic full-thickness resection of a solitary ovarian carcinoma colorectal metastasis

A woman in her 70s with a medical history of recurrent ovarian carcinoma was referred to the gastroenterologist because of rectal blood loss. Colonoscopy revealed a spontaneously bleeding lesion, which was not a typical colorectal carcinoma by optical diagnosis. Biopsies confirmed the diagnosis of recurrence of the former ovarian carcinoma. The patient was not eligible for surgical resection due to former abdominal surgery and she declined chemotherapy due to severe side effects earlier. After a multidisciplinary team consultation, she was treated with endoscopic full-thickness resection (eFTR). This is a minimally invasive resection technique for removal of challenging colorectal lesions. The patient has recovered well and 2 years after the metastasis resection with eFTR there still have been no signs of recurrent malignancy.

Ovarian cancer risk reduction by salpingectomy during non-gynaecological surgery: scoping review

Abstract Background Ovarian cancer is the leading cause of death among gynaecological cancers. The identification of the fallopian tube epithelium as the origin of most ovarian cancers introduces a novel prevention strategy by removing the fallopian tubes during an already indicated abdominal surgery for another reason, also known as an opportunistic salpingectomy. This preventive opportunity is evidence based, recommended and established at the time of gynaecologic surgery in many countries worldwide. To expand interest among surgeons in performing a salpingectomy during non-gynaecological surgery, the aim of this review is to identify knowledge gaps during those surgeries. Methods A scoping review was performed following the PRISMA-Scoping Review (ScR) checklist. PubMed, Embase, Web of Science, Cumulative Index to Nursing and Allied Health Literature (CINAHL) database and Cochrane Library were systematically searched from inception to November 2024. Trial registers were searched for ongoing trials. All studies reporting original data on salpingectomy during non-gynaecological surgery were included. Outcomes were provided narratively. Results Eighteen studies were identified reporting on the implementation, surgical feasibility, patients’ perspectives, physicians’ knowledge and cost-effectiveness of an opportunistic salpingectomy during non-gynaecological surgery. Population-level data indicate that an opportunistic salpingectomy is rarely performed in non-gynaecological surgeries. High success rates and no complications of an opportunistic salpingectomy were observed during bariatric surgery and cholecystectomies. However, performing an additional salpingectomy appeared more time-consuming. Patients had strong interest in information on and willingness to undergo opportunistic salpingectomy. Cost-effectiveness analysis encourages opportunistic salpingectomy use, as models show reduced ovarian cancer incidence and mortality rate while being cost-effective. Conclusions Opportunistic salpingectomy during non-gynaecologic surgery appears to be a promising method to prevent ovarian cancer. Implementing such a strategy will require education of multiple surgical disciplines, training and resolution of organizational issues.

Opportunistic Salpingectomy in Non‐Gynecologic Surgeries: Barriers and Facilitators From a Healthcare Provider Perspective

ABSTRACT Objective This study identifies barriers and facilitators for implementing opportunistic salpingectomy (OS) during non‐gynecological abdominal surgeries from a healthcare provider perspective. Methods From October 2023 to July 2024, a mixed‐method study was conducted. The qualitative phase involved semi‐structured focus group interviews and individual interviews with specialists in surgery (gynecologists, general surgeons, urologists, and residents) and policymakers to identify barriers and facilitators for implementing OS during non‐gynecological surgery. The quantitative phase consisted of a cross‐sectional web‐based survey assessing the importance of these barriers and facilitators. The study utilized the standardized implementation frameworks to categorize the factors into six domains: innovation, patient, healthcare professional, social setting, organization, and economic and financial context. Results In the qualitative phase, 38 healthcare professionals and policymakers identified 38 barriers and 28 facilitators. Barriers were found in all domains and mainly included increased workload, unclear invoicing, and variations in eligible surgeries. Facilitators included the poor prognosis of ovarian cancer, simplicity of OS, and availability of counseling materials. The quantitative survey revealed that 75% of gynecologists, 60% of surgeons, and 61% of urologists supported offering OS during non‐gynecological abdominal surgeries. Barriers identified included the ambiguity regarding which patients are eligible for OS, the perceived complication risks of OS, the increased workload as a result of adding OS, and the unclarity around invoicing an OS. Facilitators included the poor prognosis of ovarian cancer, the availability of uniform counseling materials, education on counseling and technical performance of OS, involvement of a gynecologist during the counseling, and clear agreements between the departments within hospitals. Conclusions Key barriers to OS implementation in non‐gynecological surgeries include unclear invoicing and increased workload, while significant facilitators are the availability of counseling materials and education on counseling and technical performance of OS. Addressing these barriers and leveraging facilitators could enhance OS adoption, potentially reducing ovarian cancer incidence.

First step in implementation of opportunistic salpingectomy for prevention of ovarian cancer: Current care and its determinants

AbstractIntroductionOpportunistic salpingectomy (OS) refers to additional removal of the fallopian tubes during abdominal surgery performed for another medical indication, as prevention for ovarian cancer. As OS has been inconsistently implemented, its clinical practice varies worldwide. To reduce this variation, insight is required into current clinical practice and its determinants. Therefore, the study aim was to determine the implementation of counseling and performance of OS between 2015 and 2018, and its patient, surgical, physician, and hospital characteristics.Material and methodsRetrospective study using electronic medical records from six different Dutch hospitals: two academic, two large teaching, and two non‐teaching hospitals. Patients were considered eligible for OS if they underwent elective non‐obstetric abdominal surgery for a gynecological indication from January 2015 through December 2018. Primary outcomes were uptake of counseling and performance of OS. Multilevel multivariable logistic regression analyses were conducted to identify characteristics associated with OS.ResultsA total of 3214 patients underwent elective non‐obstetric abdominal surgery for a gynecological indication and were eligible for OS. Counseling on OS increased significantly from 2.9% in 2015 to 29.4% in 2018. In this period, 440 patients were counseled on OS, of which 95.9% chose OS. Performance of OS increased significantly from 6.9% in 2015 to 44.5% in 2018. Counseling for and performance of OS were more likely in patients who had surgery by laparoscopic approach, were counseled by a gynecological resident, or had more than three contact moments before surgery. Additionally, OS was less likely in patients who had vaginal surgery.ConclusionsAlthough the uptake of OS increased from 2015 to 2018, the majority of patients who were eligible for OS were not counseled and did not undergo OS. Its clinical practice varies on patient, surgery, and physician characteristics. Therefore, an implementation strategy tailored to associated determinants is recommended.

External validation of Risk of Malignancy Index compared to IOTA Simple Rules

Background Mathematical predictive models for ovarian tumors have an advantage over subjective assessment due to their relative simplicity, and therefore usefulness for less experienced sonographers. It is currently unclear which predictive model is best at predicting the nature of an ovarian tumor. Purpose To compare the diagnostic predictive accuracy of the International Ovarian Tumour Analysis Simple Rules (IOTA SR) with Risk of Malignancy Index (RMI), to differentiate between benign and malignant ovarian tumors. Material and Methods A total of 202 women diagnosed with ovarian tumor(s) were included. Preoperatively, patients were examined through transvaginal ultrasonography and CA-125 (U/mL) levels were measured. RMI and IOTA SR were determined, and where possible compared to definitive histopathological diagnosis. Results Of the 202 women with ovarian tumors, 168 women were included in this cohort study. Of these tumors, 118 (70.2%) were benign, 17 (10.1%) were borderline, and 33 (19.7%) were malignant. The sensitivity, specificity, and area under the curve for the RMI were 72.0%, 90.7%, and 0.896, respectively. For the IOTA SR, these were 90.0%, 68.6%, and 0.793, respectively. Conclusion This cohort study shows that the RMI is a relatively useful diagnostic model in characterizing ovarian tumors, compared to the IOTA SR. However, due to the relatively low sensitivity of the RMI and high rate of inconclusive results of the IOTA SR, both diagnostic tests do not seem discriminative enough. Therefore, alternative diagnostic models are necessary.

The effect of opportunistic salpingectomy for primary prevention of ovarian cancer on ovarian reserve: a systematic review and meta-analysis

Opportunistic salpingectomy (OS) is an attractive method for primary prevention of ovarian cancer. Although OS has not been associated with a higher complication rate, it may be associated with earlier onset of menopause. To provide a systematic review and meta-analysis of the effect of OS on both age at menopause and ovarian reserve. A search was conducted in the Cochrane Library, Embase and MEDLINE databases from inception until March 2022. We included randomized clinical trials and cohort studies investigating the effect of OS on onset of menopause and/or ovarian reserve through change in anti-Müllerian hormone (AMH), antral follicle count (AFC), estradiol (E2), follicle stimulating hormone (FSH) and luteinizing hormone (LH). Data was extracted independently by two researchers. Random-effects meta-analyses were conducted to estimate the pooled effect of OS on ovarian reserve. The initial search yielded 1047 studies. No studies were found investigating the effect of OS on age of menopause. Fifteen studies were included in the meta-analysis on ovarian reserve. Meta-analyses did not result in statistically significant differences in mean change in AMH (MD -0.07 ng/ml, 95%CI -0.18;0.05), AFC (MD 0.20 n, 95 % CI -4.91;5.30), E2 (MD 3.97 pg/ml, 95%CI -0.92;8.86), FSH (MD 0.33mIU/ml, 95%CI -0.15;0.81) and LH (MD 0.03mIU/ml; 95%CI -0.47;0.53). Our study shows that OS does not result in a significant reduction of ovarian reserve in the short term. Further research is essential to confirm the absence of major effects of OS on menopausal onset since clear evidence on this subject is lacking. Registration number PROSPERO CRD42021260966.

Reflectance confocal microscopy as a non‐invasive imaging tool in vulvar high‐grade squamous intraepithelial lesions and lichen sclerosus: A descriptive morphological study in patients and healthy volunteers

AbstractIncorrect and delayed diagnosis of vulvar high‐grade squamous intraepithelial neoplasia (vHSIL) and lichen sclerosus (LS) increases malignant progression risks and negatively impacts prognosis and quality of life. There is a need to improve diagnosis and monitoring. Reflectance confocal microscopy is a non‐invasive imaging tool that visualizes skin structures at cellular resolution. The objectives were to explore feasibility and patient acceptability of vulvar RCM imaging and to identify RCM characteristics that are discriminative for vulvar HSIL and LS. This was a prospective, cross‐sectional, observational clinical trial in patients with vHSIL and LS compared to healthy volunteers. RCM images and vulvar tissue samples were obtained. Five (5) patients with vHSIL, 10 patients with LS and 10 healthy volunteers were enrolled. In total, 100 image series of vulvar skin were obtained, including lesional and nonlesional sites. The RCM technique was considered acceptable for application by patients and healthy controls. Healthy vulvar skin was characterized by a homogenous, normal honeycomb patterned epidermis and a clear epidermal‐dermal junctions. Vulvar HSIL and LS displayed an atypical honeycomb pattern of the epidermis and lymphocytic influx with presence of melanophages. Distinct features specifically observed in LS included the presence of hyalinised vessels and sclerotic areas in the dermis. RCM is a non‐invasive imaging technique that is feasible and clinically acceptable to apply on vulvar skin, both in patients with premalignant lesions and healthy controls. Recognition and validation of disease‐specific characteristics could make reflectance confocal microscopy a clinical tool to non‐invasively aid identification of vulvar premalignancies.

Substantial discordance between structured pre-operative computed tomography (CT) reports and intraoperative findings in advanced ovarian cancer cytoreductive surgery, affecting treatment decisions

The aim of this study was to assess the agreement and diagnostic accuracy of structured preoperative computed tomography (CT) findings compared to intraoperative findings in advanced ovarian cancer patients undergoing primary or interval cytoreductive surgery. Patients with CT scans suggesting advanced ovarian cancer were enrolled in the study. Agreement between CT reports, reviewed using European Society of Urogenital Radiology (ESUR) criteria, and surgical findings were evaluated with the kappa coefficient. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for each radiologic feature. From February 2018 to September 2020, 258 patients with International Federation of Gynaecology and Obstetrics (FIGO) stage IIIB-IV epithelial ovarian cancer were enrolled. Agreement between ESUR-reviewed CT reports and surgical findings was slight to fair (kappa = 0.115-0.352). The most common CT findings were peritoneal carcinomatosis, omental metastases, and bowel involvement. Sensitivity and specificity of peritoneal carcinomatosis were 0.91 (95% confidence interval [CI]: 0.86-0.94) and 0.19 (95% CI: 0.10-0.31), with an area under the receiver operating characteristic curve (AUC) of 0.55 (95% CI: 0.46-0.64). Omental metastases had a sensitivity of 0.91 (95% CI: 0.87-0.95) and specificity of 0.27 (95% CI: 0.16-0.40) with an AUC of 0.59 (95% CI: 0.52-0.65). Bowel involvement showed a sensitivity of 0.61 (95% CI: 0.54-0.67), specificity of 0.71 (95% CI: 0.58-0.83), and AUC of 0.66 (95% CI: 0.58-0.74). This study demonstrates limited concordance between ESUR-reviewed CT reports and intraoperative findings in advanced ovarian cancer. Even when interpreted by expert radiologists, CT imaging alone may inadequately reflect disease burden. These findings emphasise the ongoing challenges of imaging-based surgical planning and support the need for further development and validation of more accurate preoperative assessment tools.

Real-world performance of the Assessment of Different NEoplasias in the adneXa (ADNEX) model for the pre-operative classification of ovarian tumors.

To predict the risk of malignancy in ovarian tumors, the multi-class risk prediction Assessment of Different NEoplasias in the adneXa (ADNEX) model of the International Ovarian Tumor Analysis group is used internationally. This study aimed to perform an external validation of this model in a real-world clinical setting in the Netherlands. A multi-center, retrospective diagnostic accuracy study was performed. Women aged ≥18 years who attended the outpatient clinic between May 2020 and December 2021 and had a first ultrasound assessment for an ovarian tumor with application of the International Ovarian Tumor Analysis ADNEX model were included. The reference standard was the pathology result in case of surgery or follow-up with ultrasound according to the current Dutch guideline in case of conservative management. Of the 363 women included, 286 (78.8%) had benign, 24 (6.6%) had borderline, and 53 (14.6%) had malignant pathology. Most (62.5%) of the included patients underwent surgery. The area under the receiver operating characteristic (ROC) curve was 0.92 (95% CI 0.89 to 0.96) if borderline tumors were considered malignant and 0.93 (95% CI 0.89 to 0.96) if borderline tumors were considered benign. Cutoff values between 7% and 14% yielded the highest Youden index. The model was moderately able to differentiate between malignant histologic sub-types. The ADNEX model showed excellent diagnostic performance in daily clinical practice and retained its value in a population in which a proportion of patients were treated with conservative management.