PGE2 inhibits TIL expansion by disrupting IL-2 signalling and mitochondrial function.

Expansion of antigen-experienced CD8+ T cells is critical for the success of tumour-infiltrating lymphocyte (TIL)-adoptive cell therapy (ACT) in patients with cancer1. Interleukin-2 (IL-2) acts as a key regulator of CD8+ cytotoxic T lymphocyte functions by promoting expansion and cytotoxic capability2,3. Therefore, it is essential to comprehend mechanistic barriers to IL-2 sensing in the tumour microenvironment to implement strategies to reinvigorate IL-2 responsiveness and T cell antitumour responses. Here we report that prostaglandin E2 (PGE2), a known negative regulator of immune response in the tumour microenvironment4,5, is present at high concentrations in tumour tissue from patients and leads to impaired IL-2 sensing in human CD8+ TILs via the PGE2 receptors EP2 and EP4. Mechanistically, PGE2 inhibits IL-2 sensing in TILs by downregulating the IL-2Rγc chain, resulting in defective assembly of IL-2Rß-IL2Rγc membrane dimers. This results in impaired IL-2-mTOR adaptation and PGC1α transcriptional repression, causing oxidative stress and ferroptotic cell death in tumour-reactive TILs. Inhibition of PGE2 signalling to EP2 and EP4 during TIL expansion for ACT resulted in increased IL-2 sensing, leading to enhanced proliferation of tumour-reactive TILs and enhanced tumour control once the cells were transferred in vivo. Our study reveals fundamental features that underlie impairment of human TILs mediated by PGE2 in the tumour microenvironment. These findings have therapeutic implications for cancer immunotherapy and cell therapy, and enable the development of targeted strategies to enhance IL-2 sensing and amplify the IL-2 response in TILs, thereby promoting the expansion of effector T cells with enhanced therapeutic potential.

Sexual quality of life and postoperative deep dyspareunia after vNOTES benign adnexal procedures.

OBJECTIVE: This study aimed to investigate the impact of vNOTES on postoperative sexual dysfunction in patients undergoing adnexal procedures. METHODS: We analyzed data from patients who underwent vNOTES adnexal surgeries for benign conditions between May 2020 and May 2023. The primary outcome was the presence of new postoperative deep dyspareunia (DD) or other sexual dysfunctions, which were assessed through a phone survey conducted 6 to 24 months after surgery. Secondary outcomes included surgical feasibility, operative times, complications rate, and postoperative pain evaluation. RESULTS: We included 103 patients for primary and secondary outcomes and 111 patients for secondary outcomes analysis only. Newly postoperative DD was reported by three patients (2.9%), remained present at 12 postoperative months in one case (1.0%), and spontaneously disappeared in two cases (1.9%) after four and 10 postoperative months, respectively. In the remaining 100 patients (97.1%), no new DD or other sexual function disorders were reported after surgery. vNOTES procedures were successfully performed in all cases, with a mean operative time of 38.2 ± 19.6 min and a conversion rate to conventional laparoscopy of 0.9%. No significant complication was observed. CONCLUSION: This study suggests a very limited risk of developing postoperative sexual dysfunction after vNOTES benign adnexal procedures.

Consensus on surgical technique for sentinel lymph node dissection in cervical cancer.

OBJECTIVE: The purpose of this study was to establish a consensus on the surgical technique for sentinel lymph node (SLN) dissection in cervical cancer. METHODS: A 26 question survey was emailed to international expert gynecological oncology surgeons. A two-step modified Delphi method was used to establish consensus. After a first round of online survey, the questions were amended and a second round, along with semistructured interviews was performed. Consensus was defined using a 70% cut-off for agreement. RESULTS: Twenty-five of 38 (65.8%) experts responded to the first and second rounds of the online survey. Agreement ≥70% was reached for 13 (50.0%) questions in the first round and for 15 (57.7%) in the final round. Consensus agreement identified 15 recommended, three optional, and five not recommended steps. Experts agreed on the following recommended procedures: use of indocyanine green as a tracer; superficial (with or without deep) injection at 3 and 9 o'clock; injection at the margins of uninvolved mucosa avoiding vaginal fornices; grasping the cervix with forceps only in part of the cervix is free of tumor; use of a minimally invasive approach for SLN biopsy in the case of simple trachelectomy/conization; identification of the ureter, obliterated umbilical artery, and external iliac vessels before SLN excision; commencing the dissection at the level of the uterine artery and continuing laterally; and completing dissection in one hemi-pelvis before proceeding to the contralateral side. Consensus was also reached in recommending against injection at 6 and 12 o'clock, and injection directly into the tumor in cases of the tumor completely replacing the cervix; against removal of nodes through port without protective maneuvers; absence of an ultrastaging protocol; and against modifying tracer concentration at the time of re-injection after mapping failure. CONCLUSION: Recommended, optional, and not recommended steps of SLN dissection in cervical cancer have been identified based on consensus among international experts. These represent a surgical guide that may be used by surgeons in clinical trials and for quality assurance in routine practice.

External beam radiotherapy boost versus surgical debulking followed by radiotherapy for the treatment of metastatic lymph nodes in cervical cancer: A systematic review and meta-analysis.

OBJECTIVE: We aimed to assess disease-free survival (DFS), overall survival (OS) and treatment-related toxicity of two therapeutic strategies for treating bulky lymph nodes on imaging in patients with locally advanced cervical cancer (LACC): radiotherapy boost versus surgical debulking followed by radiotherapy. METHODS: We performed a systematic review of studies published up to October 2023. We selected studies including patients with LACC treated by external beam radiotherapy (EBRT) boost or lymph node debulking followed by EBRT (with or without boost). RESULTS: We included two comparative (included in the meta-analysis) and nine non-comparative studies. The estimated 3-year recurrence rate was 28.2% (95%CI:18.3-38.0) in the EBRT group and 39.9% (95%CI:22.1-57.6) in the surgical debulking plus EBRT group. The estimated 3-year DFS was 71.8% and 60.1%, respectively (p = 0.19). The estimated 3-year death rate was 22.2% (95%CI:11.2-33.2) in the EBRT boost group and 31.9% (95%CI:23.3-40.5) in the surgical debulking plus EBRT group. The estimated 3-year OS was 77.8% and 68.1%, respectively (p = 0.04). No difference in lymph node recurrence between the two comparative studies (p = 0.36). The meta-analysis of the two comparative studies showed no DFS difference (p = 0.13) but better OS in the radiotherapy boost group (p = 0.006). The incidence of grade≥3 toxicities (ranging 0-50%) was not different between the two approaches in the two comparative studies (p = 0.31). CONCLUSION: No DFS and toxicity difference when comparing EBRT boost with surgical debulking of enlarged lymph nodes and EBRT in patients with cervical cancer was evident. Radiotherapy boost had better OS. Further investigation is required to better understand the prognostic role of surgical lymph node debulking in light of radiotherapy developments.

Contribution of preoperative ultrasound-guided implantation of a magnetic seed for optimal localization and resection of vulvar angiosarcoma: A case report.

INTRODUCTION: Vulvar cancer is a rare cause of malignancy among women. It is key for surgeons to achieve negative resection margins, as it greatly impacts patient's prognosis. Unfortunately, additional surgical procedures are often performed due to the regional anatomical complexity. Based on non-palpable breast tumors, where image-guided preoperative localization tools have enhanced the complete resection rates, we aimed at evaluating the feasibility of magnetic seed technique for localizing perineal lesions. PRESENTATION OF THE CASE: We present the case of a 40-year-old female patient, who underwent iterative resections for a recurrent epithelioid angiosarcoma of the left labia major. Imaging revealed a suspicious regional involvement at 3 months of follow-up, for which another surgery was planned. We decided to target this non-palpable lesion with the Magnetic Seed technique to guide the intervention. A seed was inserted into the nodule under ultrasound guidance. Resection was then performed, with negative margins and no recurrence on last follow-up. DISCUSSION: Surgical procedures with minimal extension are recommended in vulvar cancer, to limit the aesthetic and functional complication. Unfortunately, recurrences and residual tumors remain frequent, even higher when surgical margin safety is not achieved. Many studies have suggested the benefit of image-guided localization tools in non-palpable breast tumors. By reducing the excising volume and focusing on the lesions, relapse and complications are rarer. We considered Magnetic Seed to be the most appropriated technique for perineal lesions. CONCLUSION: As for breast cancer, Magnetic Seed technique could be appropriate for non-palpable perineal lesions, optimizing resection margins with minimal procedures.

Predictors of Non-Sentinel Lymph Node Metastasis in Patients with Positive Sentinel Lymph Node in Early-Stage Cervical Cancer: A SENTICOL GROUP Study.

BACKGROUND: The goal of this study was to identify the risk factors for metastasis in the remaining non-sentinel lymph nodes (SLN) in the case of positive SLN in early-stage cervical cancer. METHODS: An ancillary analysis of two prospective multicentric databases on SLN biopsy for cervical cancer (SENTICOL I and II) was performed. Patients with early-stage cervical cancer (FIGO 2018 IA to IIA1), with bilateral SLN detection and at least one positive SLN after ultrastaging, were included. RESULTS: 405 patients were included in SENTICOL I and Il. Fifty-two patients had bilateral SLN detection and were found to have SLN metastasis. After pelvic lymphadenectomy, metastatic involvement of non-SLN was diagnosed in 7 patients (13.5%). Patients with metastatic non-SLN were older (51.9 vs. 40.8 years, p = 0.01), had more often lympho-vascular space invasion (LVSI) (85.7% vs. 35.6%, p = 0.03), and had more often parametrial involvement (42.9% vs. 6.7%, p = 0.003). Multivariate analysis retained age (OR = 1.16, 95% IC = [1.01-1.32], p = 0.03) and LVSI (OR = 25.97, 95% IC = [1.16-582.1], p = 0.04) as independently associated with non-SLN involvement. CONCLUSIONS: Age and LVSI seemed to be predictive of non-SLN metastasis in patients with SLN metastasis in early-stage cervical cancer. Larger cohorts are needed to confirm the results and clinical usefulness of such findings.

Survival after sentinel lymph node biopsy for early cervical cancers: a systematic review and meta-analysis.

BACKGROUND: Sentinel lymph node biopsy represents an alternative to pelvic lymphadenectomy for lymph node staging of early-stage cervical carcinoma, but prospective evidence on long-term oncological safety of sentinel lymph node biopsy alone versus pelvic lymphadenectomy is missing. OBJECTIVE: To investigate, with this meta-analysis, the impact of sentinel lymph node biopsy alone versus pelvic lymphadenectomy on survival for patients with early-stage cervical cancer. METHODS: A systematic literature review was performed. We excluded studies in which pelvic lymphadenectomy was systematically performed after every sentinel lymph node biopsy, including only articles where pelvic lymphadenectomy was performed because sentinel lymph node biopsy was not conclusive. A meta-analysis was carried out combining 5-year disease-free survival and overall survival rates with a random and fixed effect model. Heterogeneity was tested using the Cochran Χ2 test and quantified with Higgins information I2. RESULTS: The search of databases and registers found 927 items and six articles (two retrospective and four prospective). The median time of follow-up was 34.8 months (range 13-53). Overall common effect disease-free survival was 98% while random effect disease-free survival was 94%. Overall heterogeneity was 77%. A subgroup analysis was applied, dividing studies into one group including sentinel lymph node biopsy negative data only (common effect disease-free survival 91%; random effect disease-free survival 90%), and one group with a negative and positive sentinel lymph node biopsy (common effect disease-free survival 98%; random effect disease-free survival 96%). In the analysis of overall survival, positive and negative sentinel lymph node biopsy cases were examined together (common and random effect overall survival 99%). Ultrastaging did not affect disease-free survival (common and random effect disease-free survival 92% in the ultrastaging group vs common effect disease-free survival 99% and random effect disease-free survival 96% in the non-ultrastaging group). CONCLUSIONS: Both 5-year disease-free survival and overall survival rate after sentinel lymph node biopsy alone are higher than 90% and do not differ from pelvic lymphadenectomy survival data. Ultrastaging did not impact survival.

ESGO/ESTRO/ESP Guidelines for the management of patients with cervical cancer - Update 2023.

In 2018, the European Society of Gynecological Oncology (ESGO) jointly with the European Society for Radiotherapy and Oncology (ESTRO) and the European Society of Pathology (ESP) published evidence-based guidelines for the management of patients with cervical cancer. Given the large body of new evidence addressing the management of cervical cancer, the three sister societies jointly decided to update these evidence-based guidelines. The update includes new topics to provide comprehensive guidelines on all relevant issues of diagnosis and treatment in cervical cancer. To serve on the expert panel (27 experts across Europe) ESGO/ESTRO/ESP nominated practicing clinicians who are involved in managing patients with cervical cancer and have demonstrated leadership through their expertise in clinical care and research, national and international engagement, profile, and dedication to the topics addressed. To ensure the statements were evidence based, new data identified from a systematic search was reviewed and critically appraised. In the absence of any clear scientific evidence, judgment was based on the professional experience and consensus of the international development group. Before publication, the guidelines were reviewed by 155 independent international practitioners in cancer care delivery and patient representatives. These updated guidelines are comprehensive and cover staging, management, follow-up, long-term survivorship, quality of life and palliative care. Management includes fertility sparing treatment, early and locally advanced cervical cancer, invasive cervical cancer diagnosed on a simple hysterectomy specimen, cervical cancer in pregnancy, rare tumors, recurrent and metastatic diseases. The management algorithms and the principles of radiotherapy and pathological evaluation are also defined.

ESGO/ESTRO/ESP Guidelines for the management of patients with cervical cancer - Update 2023.

In 2018, the European Society of Gynecological Oncology (ESGO) jointly with the European Society for Radiotherapy and Oncology (ESTRO) and the European Society of Pathology (ESP) published evidence-based guidelines for the management of patients with cervical cancer. Given the large body of new evidence addressing the management of cervical cancer, the three sister societies jointly decided to update these evidence-based guidelines. The update includes new topics to provide comprehensive guidelines on all relevant issues of diagnosis and treatment in cervical cancer.To serve on the expert panel (27 experts across Europe) ESGO/ESTRO/ESP nominated practicing clinicians who are involved in managing patients with cervical cancer and have demonstrated leadership through their expertise in clinical care and research, national and international engagement, profile, and dedication to the topics addressed. To ensure the statements were evidence based, new data identified from a systematic search was reviewed and critically appraised. In the absence of any clear scientific evidence, judgment was based on the professional experience and consensus of the international development group. Before publication, the guidelines were reviewed by 155 independent international practitioners in cancer care delivery and patient representatives.These updated guidelines are comprehensive and cover staging, management, follow-up, long-term survivorship, quality of life and palliative care. Management includes fertility sparing treatment, early and locally advanced cervical cancer, invasive cervical cancer diagnosed on a simple hysterectomy specimen, cervical cancer in pregnancy, rare tumors, recurrent and metastatic diseases. The management algorithms and the principles of radiotherapy and pathological evaluation are also defined.

ESGO/ESTRO/ESP Guidelines for the management of patients with cervical cancer - Update 2023.

In 2018, the European Society of Gynecological Oncology (ESGO) jointly with the European Society for Radiotherapy and Oncology (ESTRO) and the European Society of Pathology (ESP) published evidence-based guidelines for the management of patients with cervical cancer. Given the large body of new evidence addressing the management of cervical cancer, the three sister societies jointly decided to update these evidence-based guidelines. The update includes new topics to provide comprehensive guidelines on all relevant issues of diagnosis and treatment in cervical cancer.To serve on the expert panel (27 experts across Europe) ESGO/ESTRO/ESP nominated practicing clinicians who are involved in managing patients with cervical cancer and have demonstrated leadership through their expertise in clinical care and research, national and international engagement, profile, and dedication to the topics addressed. To ensure the statements were evidence based, new data identified from a systematic search was reviewed and critically appraised. In the absence of any clear scientific evidence, judgment was based on the professional experience and consensus of the international development group. Before publication, the guidelines were reviewed by 155 independent international practitioners in cancer care delivery and patient representatives.These updated guidelines are comprehensive and cover staging, management, follow-up, long-term survivorship, quality of life and palliative care. Management includes fertility sparing treatment, early and locally advanced cervical cancer, invasive cervical cancer diagnosed on a simple hysterectomy specimen, cervical cancer in pregnancy, rare tumors, recurrent and metastatic diseases. The management algorithms and the principles of radiotherapy and pathological evaluation are also defined.

TRANSLACOL project: Nodal human papillomavirus tumoral DNA detection by ddPCR for survival prediction in early cervical cancer patients without pelvic lymph node invasion.

INTRODUCTION: In early cervical cancer (EEC), 10 to 15% of patients without nodal metastasis (N-) will suffer from recurrences with further similar survival as N+ patients. However, no clinical, imaging or pathological risk-factor is today available to identify them. In the present study, we hypothesized that the N- histologically characterized patients who present a poor prognosis could be patients for whom metastasis are missed by classical procedure. Therefore, we propose to research HPV tumoral DNA (HPVtDNA) in pelvic Sentinel Lymph Nodes (SLN) biopsy using ultrasensitive droplet-based digital PCR (ddPCR) to detect eventual occult metastasis. MATERIALS AND METHODS: Sixty HPV16, HPV18 or HPV33 positive EEC N- patients with available SLN were included. In SLN, HPV16 E6, HPV18 E7 and HPV33 E6 gene were respectively detected using ultrasensitive ddPCR technology. Survival data were analysed using Kaplan-Meier-curves and log-rank-test to compare progression-free survival (PFS) and disease-specific survival (DSS) in two groups according to their HPVtDNA status in SLN. RESULTS: More than half (51.7%) of the patients finally showed HPVtDNA positivity in SLN initially diagnosed as negative by histology. Two patients with negative HPVtDNA SLN and 6 with positive HPVtDNA SLN group presented recurrence. Finally, all of the 4 deaths listed in our study occurred in the positive HPVtDNA SLN group. CONCLUSION: These observations hint that the use of ultrasensitive ddPCR to detect HPVtDNA in SLN could allow the identification of two subgroups of histologically N- patients that may have different prognosis and outcome. To our knowledge, our study is the first one to evaluate the detection of HPVtDNA in SLN in early cervical cancer using ddPCR highlighting its interest as a complementary tool for N- specific early cervical cancer diagnosis.

Safety and efficacy of a suction cervical stabilizer for intrauterine contraceptive device insertion: Results from a randomized, controlled study.

OBJECTIVES: To compare patient-reported pain, bleeding, and device safety between intrauterine contraceptive device (IUD) insertion procedures employing a suction cervical stabilizer or single-tooth tenaculum. STUDY DESIGN: This was a randomized, prospective, single-blinded study conducted at two centers, enrolling women aged 18 years or older, eligible for IUD insertion. The primary end point measure was patient-reported pain, measured on a 100-mm Visual Analogue Scale. Safety was assessed on the amount of bleeding, adverse events, and serious adverse events. RESULTS: One hundred women were randomized, 48 to the investigational device and 52 to control. There were no statistically significant differences between the groups in factors potentially associated with pain on IUD insertion. IUD insertion was successful in 94% of all subjects. Subjects in the investigational device group reported pain scores ≥14 points lower than in the control group at cervix grasping (14.9 vs 31.3; p < 0.001) and traction (17.0 vs 35.9; p < 0.001), and smaller differences in pain scores at the IUD insertion (31.5 vs 44.9; p = 0.021) and cervix-release (20.6 vs 30.9; p = 0.049) steps. Nulliparous women experienced the greatest pain differences to control. Mean blood loss was 0.336 (range 0.022-2.189) grams in the investigational device group and 1.336 (range 0.201-11.936) grams in the control group, respectively (p = 0.03 for the comparison). One adverse event (bruising and minor bleeding) in the investigational device group was considered causally related to the study device. CONCLUSIONS: The suction cervical stabilizer had a reassuring safety profile and its use was associated with significant reductions in pain during the IUD insertion procedure compared with standard single-tooth tenaculum use, particularly among nulliparous women. IMPLICATIONS: Pain can be an important barrier to greater use of IUD devices among prescribers and users, particularly nulliparous women. The suction cervical stabilizer may provide an appealing alternative to currently available tenacula, filling an important unmet need.

Lymph Node Involvement in Recurrent Serous Borderline Ovarian Tumors: Current Evidence, Controversies, and a Review of the Literature.

Borderline ovarian tumors (BOTs) account for 10-20% of epithelial ovarian neoplasms. They are characterized by their lack of destructive stromal invasion. In comparison to invasive ovarian cancers, BOTs occur in younger patients and have better outcome. Serous borderline ovarian tumor (SBOT) represents the most common subtype of BOT. Complete surgical staging is the current standard management but fertility-sparing surgery is an option for SBOT patients who are at reproductive age. While most cases of SBOTs have an indolent course with favorable prognosis, late recurrence and malignant transformation can occur, usually in the form of low-grade serous carcinoma (LGSC). Thus, assessment of the recurrence risk is essential for the management of those patients. SBOTs can be associated with lymph node involvement (LNI) in up to 30% of patients who undergo lymph node dissection at diagnosis, and whether LNI affects prognosis is controversial. The present review suggests that recurrent SBOTs with LNI have poorer oncological outcomes and highlights the biases due to the scarcity of reports in the literature. Preventing SBOTs from recurring and becoming invasive overtime and a more profound understanding of the underlying mechanisms at play are necessary.

Management of patients with advanced epithelial ovarian cancer: a European survey.

BACKGROUND: The aim of this study was to assess current European practices in the management of patients with advanced epithelial ovarian cancer in 2021. METHODS: A 58-question electronic survey was distributed anonymously to the members of six European learned societies. Initial diagnostic workup and staging, pathological data, surgical data, treatments and follow-up strategies were assessed. RESULTS: A total of 171 participants from 17 European countries responded to emailed surveys. Most participants were experienced practitioners (superior than 15 years of experience) specializing in gynecology-obstetrics (29.8%), surgical oncology (25.1%), and oncogynecology (21.6%). According to most (64.8%) participants, less than 50% of patients were eligible for primary debulking surgery. Variations in the rate of primary debulking surgery depending on the country of origin of the practitioners were observed in this study. The LION study criteria were applied in 70.4% of cases during PDS and 27.1% after chemotherapy. In cases of BRCA1-2 mutations, olaparib was given by 75.0-84.8% of respondents, whereas niraparib was given in cases of BRCA wild-type diseases. CONCLUSIONS: This study sheds light on current practices and attitudes regarding the management of patients with advanced epithelial ovarian cancer in Europe in 2021.

[Application in France of the 2021 European recommendations on endometrial cancer]. / Application en France des recommandations européennes 2021 sur le cancer de l'endomètre.

The latest European recommendations of the European Societies of Gynecological Oncology (ESGO), Radiotherapy and Oncology (ESTRO) and Anatomopathology (ESP) concerning the management of patients with endometrial cancer were published in 2021. On behalf of the French Society of Gynecologic Oncology (SFOG) and the SFOG campus, we wish to summarize for the French-speaking readership the main measures with a more specific application for France. We also incorporate data from a Delphi survey conducted with a panel of French and French-speaking Swiss experts. The data presented in this article relate to histo-molecular characteristics, radiological data of endometrial cancer, and management of low-risk, intermediate-risk, intermediate-high-risk, and metastatic cancers. The aim of this review article is to show the application of the latest international recommendations to clinicians and pathologists for the implementation of these recommendations.

Ulcus Vulvae Acutum Lipschütz-UVAL: case series at a Swiss university hospital emergency room.

Background: Ulcus Vulvae Acutum Lipschütz (UVAL) is a largely unknown disease with a broad and complex differential diagnosis. Objectives: To provide a description of the main characteristics of UVAL, determine the most appropriate diagnostic process and describe the current therapeutic approach. Methods: We designed a retrospective, descriptive cohort study using the gynecological-ER database of our institution. Inclusion criteria: female patients aged between 10 and 20 years old with suspicion of a UVAL diagnosis at CHUV's gynecological ER. Data extraction: epidemiological characteristics, clinical presentation, laboratory tests, established diagnostics, treatment, and ulcer outcomes. Results: 15 patients were included for the analysis; average age: 15 years old; 60% of patients were virgo at the time of ulcer onset; all patients had at least one flu-like symptom concomitant with the vulvar lesion; the most-performed serology was for EBV and acute disease was present in only one patient; for diagnostic purposes two biopsies were performed with both inconclusive histopathology analysis; the main prescribed treatments were: oral NSAIDs, Paracetamol, and Lidocaine gel; 93% of cases presented signs of regression; the average follow-up time was 10 days. The diagnostic algorithm of Sadoghi et al: 10 out of 15 cases were retrospectively diagnosed with UVAL by the algorithm; half were diagnosed with UVAL, and the other half received a diagnosis of "ulcers of unknown origin" at the time of the gynecological ER visit. Conclusions: We highly recommend the diagnostic and therapeutic algorithms developed by Sadoghi et al. as valuable tools to guide clinical reasoning and, consequently, improve acute vulvar ulcers management.

Management of Endometrial Cancer: French Society of Onco-Gynecology's Evaluation through a Delphi Survey.

Our aim was to assess the opinion of a panel of experts and obtain a consensus on the management of endometrial cancer in France and French Switzerland. A Delphi survey was carried out among a panel of French and French-speaking Swiss experts. The first questionnaire included 65 questions divided into eight categories: characterization of experts, histo-molecular characteristics and radiological data of endometrial cancer, and management of low-risk, intermediate-risk, intermediate-high-risk, high-risk, and metastatic cancers. The experts were asked to reply on a 9-point scale, both on the validity and the clarity of each question. After the answers were analyzed, a second questionnaire was sent to the same experts. The study took place between December 2021 and March 2022. Further, 58 (57.4%) of the 101 experts responded in the first round, and 39 recommendations were obtained (60%). Six questions were voted redundant and 20 discordant. These questions were reformulated, and, at the end of the second round, 17 recommendations were validated (85%). In total, the study presents an analysis of 56 questions and related responses. Expert advice helps to clarify non-consensual issues, standardize the management of endometrial cancer, and optimize clinical practices.

Histological regression of peritoneal metastases of recurrent tubo-ovarian cancer after systemic chemotherapy.

Introduction: Post-treatment histological regression of peritoneal metastases (PM) is a new and potentially important predictor of oncological outcomes. Histology of PM from adnexal origin is usually evaluated by the Chemotherapy Response Score (CRS). The aim of this preliminary study was to quantify the response of PM of recurrent tubo-ovarian cancer (TOVC) after systemic chemotherapy by using the recently validated Peritoneal Regression Grading System (PRGS) and compare it with CRS. Correlation with per operative evaluation through Peritoneal Cancer Index (PCI) was performed. Material and methods: Retrospective cohort study of all consecutive patients with recurrent PM from TOVC undergoing surgery after prior systemic chemotherapy from January 2015 to March 2019. Biopsies were assessed with the four-scale PRGS. Results: Thirty-eight patients were included. Patients had a median of 2 (range 1-2) lines and 12 (range 3-18) cycles of prior systemic chemotherapy. Overall mean (SD) PRGS was 2.3 (±1.1). Of the patients, 26% (10) had complete response (PRGS 1), 40% (15) had major response (PRGS 2), 26% (10) minor response (PRGS 3), and 8% (3) had no response (PRGS 4). Mean PRGS was positively correlated with the Peritoneal Cancer Index (ρ = 0.5302, p = 0.0003) and inversely correlated with CRS (ρ = -0.8403, p < 0.0001). No correlation was highlighted between mean PRGS and overall survival (ρ = -0.0195, p = 0.9073). Conclusion: CRS and mean PRGS correlated with each other. Histological response of PM after systemic chemotherapy was quantifiable and variable. The role of PRGS for the evaluation of treatment response and as potential surrogate marker for oncological outcomes is part of ongoing and planned research.

Women with Cervical High-Risk Human Papillomavirus: Be Aware of Your Anus! The ANGY Cross-Sectional Clinical Study.

Anogenital human papillomaviruses (HPV) are highly prevalent in sexually active populations, with HR-HPV being associated with dysplasia and cancers. The consequences of cervical HPV infection are well-known, whereas those of the anus are less clear. The correlation of cervical and anal HPVs with the increasing number of anal cancers in women has not been studied yet. The objective of our prospective study was to determine whether cervical and anal HPV correlated in a cohort of women recruited in a university hospital in Switzerland. Recruitment was conducted in the gynecology clinic, the colposcopy clinic, and the HIV clinic. Cervical and anal HPV genotyping and cytology were performed. Overall, 275 patients were included (360 were initially planned), and among them, 102 (37%) had cervical HR-HPV. Patients with cervical HR-HPV compared to patients without cervical HR-HPV were significantly younger (39 vs. 44 yrs, p < 0.001), had earlier sexual intercourse (17.2 vs. 18.3 yrs, p < 0.01), had more sexual partners (2.9 vs. 2.2, p < 0.0001), more dysplastic cervical cytology findings (42% vs. 19%, p < 0.0001) and higher prevalence of anal HR-HPV (59% vs. 24%, p < 0.0001). Furthermore, the HR-HPV group reported more anal intercourse (44% vs. 29%, p < 0.015). Multivariate analysis retained anal HR-HPV as independent risk factor for cervical HR-HPV (OR3.3, CI 1.2−9.0, p = 0.02). The results of this study emphasize that it is of upmost importance to screen women for anal HR-HPV when diagnosing cervical HR-HPV.