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.

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.

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.

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.

HIV testing in termination of pregnancy and colposcopy services: a scoping review.

BACKGROUND: Women and girls are relatively under-represented across the HIV treatment cascade. Two conditions unique to women, pregnancy and cervical cancer/dysplasia, share a common acquisition mode with HIV. This scoping review aimed to explore HIV testing practices in voluntary termination of pregnancy (TOP) and colposcopy services. METHODS: The scoping review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews. We searched articles published up to 20 December 2020 using three electronic databases (PubMed/Medline, Embase, Google Scholar) and including the keywords "HIV Testing", "Abortion, Induced", "Colposcopy", "HIV screen*" and "termination of pregnancy". RESULTS: A total of 1496 articles were identified, of which 55 met the inclusion criteria. We included studies providing background HIV prevalence in addition to prevalence in the study population and studies of women seeking TOP rather than presenting with TOP complications. This limited our review to high-income, low HIV prevalence settings. We observed two study phases: studies pre-antiretroviral therapy (ART) using unlinked anonymous testing data and examining HIV risk factors associated with positive HIV tests and studies post-ART using routine testing data and exploring HIV testing uptake. HIV prevalence was estimated at >0.2% in most TOP settings and >1% (range 1.7%-11.4%) in colposcopy services. Many TOP providers did not have local HIV testing policies and HIV testing was not mentioned in many specialist guidelines. Testing uptake was 49%-96% in TOP and 23%-75% in colposcopy services. CONCLUSION: Given the estimated HIV prevalence of >0.1% among women attending TOP and colposcopy services, HIV testing would be economically feasible to perform in high-income settings. Explicit testing policies are frequently lacking in these two settings, both at the local level and in specialist guidelines. Offering HIV testing regardless of risk factors could normalise testing, reduce late HIV presentation and create an opportunity for preventive counselling.

Long-term oncological safety of sentinel lymph node biopsy in early-stage cervical cancer: A post-hoc analysis of SENTICOL I and SENTICOL II cohorts.

OBJECTIVES: To compare oncologic outcomes of patients with early-stage cervical cancer and negative nodes who underwent sentinel lymph node biopsy alone (SLNB) versus pelvic lymphadenectomy (PL). METHODS: An ancillary analysis of two prospective multicentric trials on SLN biopsy for cervical cancer (SENTICOL I and II) was conducted. Only patients with early-stage cervical cancer (IA to IIA FIGO stage), bilateral detection of SLN, negative SLN after ultrastaging and negative non-SLN after final pathologic examination were included. Risk-factors of recurrence and disease-specific mortality were determined by Cox proportional hazard models. RESULTS: Between January 2005 and July 2012, 259 node-negative patients were analyzed: 87 in the SLNB group and 172 in the PL group. The median follow-up was 47 months [4-127]. During the follow-up, 21 patients (8.1%) experienced recurrences, including 4 nodal recurrences (1.9%), and 9 patients (3.5%) died of cervical cancer. Disease-free survival (DFS) and disease-specific survival (DSS) were similar between SLNB and PL groups, 85.1% vs. 80.4%, p = 0.24 and 90.8% vs. 97.2%, p = 0.22 respectively. By Cox multivariate analysis, SLNB compared to PL was not associated with DFS (HR = 1.78, 95%CI = [0.71-4.46], p = 0.22) neither with DSS (HR = 3.02, 95%CI = [0.69-13.18], p = 0.14). Only pathologic risk level according to the Sedlis criteria was an independent predictor of DFS and DSS. CONCLUSIONS: Omitting full pelvic lymphadenectomy for patients with bilateral negative SLN does not seem to be associated with an increased risk of recurrence in this series. Survival non-inferiority needs to be confirmed by prospective trials.

Clinical impact of low-volume lymph node metastases in early-stage cervical cancer: A comprehensive meta-analysis.

OBJECTIVE: In order to define the clinical significance of low-volume metastasis, a comprehensive meta-analysis of published data and individual data obtained from articles mentioning micrometastases (MIC) and isolated tumor cells (ITC) in cervical cancer was performed, with a follow up of at least 3 years. METHODS: We performed a systematic literature review and meta-analysis, following Cochrane's review methods guide and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The primary outcome was the disease-free survival (DFS), and the secondary outcome was the overall survival (OS). The hazard ratio (HR) was taken as the measure of the association between the low-volume metastases (MIC+ITC and MIC alone) and DFS or OS; it quantified the hazard of an event in the MIC (+/- ITC) group compared to the hazard in node-negative (N0) patients. A random-effect meta-analysis model using the inverse variance method was selected for pooling. Forest plots were used to display the HRs and risk differences within individual trials and overall. RESULTS: Eleven articles were finally retained for the meta-analysis. In the analysis of DFS in patients with low-volume metastasis (MIC + ITC), the HR was increased to 2.60 (1.55-4.34) in the case of low-volume metastasis vs. N0. The presence of MICs had a negative prognostic impact, with an HR of 4.10 (2.71-6.20) compared to N0. Moreover, this impact was worse than that of MIC pooled with ITCs. Concerning OS, the meta-analysis shows an HR of 5.65 (2.81-11.39) in the case of low-volume metastases vs. N0. The presence of MICs alone had a negative effect, with an HR of 6.94 (2.56-18.81). CONCLUSIONS: In conclusion, the presence of MIC seems to be associated with a negative impact on both the DFS and OS and should be treated as MAC.

[Vaginal microbiota and vaginosis]. / Microbiote vaginal et vaginose.

The vaginal microbiota is essentially composed of bacteria of the Lactobacillus genus. These bacteria, by their presence, prevent vaginal contamination by other potentially aggressive germs. Disturbances of the microbiota lead to a pathological state called dysbiosis, one of the most frequent pathogenic aspects of which is bacterial vaginosis. This vaginal state results in nauseating leucorrhoea induced by the proliferation of aero-anaerobic bacteria. Bacterial vaginosis is a source of different clinical impacts: increased risk of genital infection with many pathogens, loss of chance in medically assisted procreation, increased risk of premature delivery. The treatment of bacterial vaginosis must take into account the restitution of a normal microbiota.

Le microbiote vaginal est composé de bactéries du genre Lactobacillus. Ces bactéries empêchent la contamination vaginale par d'autres germes potentiellement agressifs. Les perturbations du microbiote aboutissent à un état pathologique dénommé dysbiose, dont un des aspects pathogènes le plus fréquent est la vaginose bactérienne (VB). La VB se traduit par des leucorrhées nauséabondes induites par la prolifération de bactéries aéro-anaérobies. La VB est source de différents impacts cliniques : majoration du risque infectieux génital, pertes de chance en procréation médicalement assistée, accroissement du risque d'accouchement prématuré… Le traitement de la VB doit prendre en compte la restitution d'un microbiote normal.

[Human Papillomavirus: screening of cervical and anal cancers]. / Papillomavirus humain : dépistage des cancers du col et de l'anus.

Cervical cancer is preventable through primary and secondary prevention. Vaccination against the human papillomavirus (HPV), the virus necessary for the development of precancerous lesions, can prevent most of them. Screening by cytology for these precancerous (or cancerous) lesions can be replaced by screening for certain types of HPV, high risk (HR-HPV), causing cervical cancer. The presence of HR-HPV on the cervix should raise suspicion of concomitant infection in the anus, as both epithelia are highly susceptible. This attitude is dictated by the increase incidence in anal cancer in the population, which is also HPV-dependent and therefore also potentially preventable through vaccination and screening.

Le cancer du col utérin est évitable, au travers d'une politique de prévention primaire et secondaire. Une vaccination contre le papillomavirus humain (HPV), et plus particulièrement contre les HPV dits à haut risque (HR-HPV) qui induisent le développement des états précancéreux, permet ainsi d'éviter une majeure partie de ceux-ci. Un dépistage par cytologie à la recherche de ces lésions précancéreuses (ou cancéreuses) peut être supplanté par la recherche de la présence des HR-HPV. La présence de HR-HPV sur le col doit faire suspecter une infection concomitante au niveau de l'anus car les deux épithéliums y sont très sensibles. Cette attitude est dictée par l'augmentation des cancers de l'anus dans la population, cancer lui aussi dépendant du HPV, et donc aussi potentiellement évitable au travers de la vaccination et du dépistage.

[Pregnancy of undetermined location: how to find it?] / Grossesse de localisation indéterminée : comment la trouver ?

Early pregnancy is frequently accompanied by abnormal symptoms such as pelvic pain and metrorrhagia. In these situations, it is quite frequent to be unable to identify the pregnancy and in particular its location, even if the pregnancy test is clearly positive. Many clinical, biological and ultrasound approaches have been proposed to try to predict the location and development of the suspected pregnancy, without the individualization of a truly reliable tool. Currently the HCG dosage at 48 heures-interval remains one of the best tools available, but it is challenged by mathematical models such as the M6 model. The M6 model has shown in our experience a very good predictive value with also an ability to reduce the follow-up of patients with low progressive risk, thus allowing a reduction in costs and anxiety for patients and caregivers.

Le début des grossesses est fréquemment accompagné de symptômes anormaux tels que douleurs pelviennes et métrorragies. Dans ces situations, il n'est pas rare de ne pas pouvoir identifier la grossesse et, en particulier, sa localisation même si le test de grossesse est nettement positif. De nombreuses approches clinique, biologique et échographique ont été proposées pour essayer de prédire la localisation et l'évolutivité de la grossesse suspectée, sans individualisation d'un outil vraiment fiable. Actuellement, le dosage de HCG à 48 heures d'intervalle reste un des meilleurs outils disponibles, mais il est concurrencé par des modèles mathématiques comme le M6. Ce dernier a démontré, selon notre expérience, une très bonne valeur prédictive avec aussi une capacité à réduire le suivi des patientes à faible risque évolutif, en permettant ainsi une baisse des coûts et de l'anxiété des patientes et soignants.

[Intraperitoneal therapy for carcinomatosis in ovarian cancer: proposed treatment algorithm]. / Traitements intrapéritonéaux de la carcinose ovarienne : proposition d'algorithmes décisionnels.

Ovarian cancer is the first cause of death by gynecological cancer. Most of the patients are diagnosed with peritoneal carcinomatosis that represents a therapeutic challenge. Its management implies maximal cytoreductive surgery with survival benefit. Over the last three decades, several strategies of intra-peritoneal chemotherapy have been investigated. This includes intra-peritoneal adjuvant chemotherapy that is used mainly in North America, hyperthermic intraperitoneal chemotherapy (HIPEC) and more recently pressurized intraperitoneal aerosol chemotherapy (PIPAC). In the current article, we review the evidence in favor of each therapeutic approach, and we propose treatment algorithms depending on the clinical situation of ovarian cancer patients: upfront, platinum-sensitive and platinum-resistant relapse.

Le cancer de l'ovaire est la première cause de décès par cancer gynécologique. La plupart des patientes sont diagnostiquées au stade de carcinose péritonéale qui représente un défi thérapeutique. Sa prise en charge chirurgicale implique une cytoréduction maximaliste. Au cours des 30 dernières années, plusieurs stratégies de chimiothérapie intrapéritonéale ont été testées afin d'améliorer le contrôle de la carcinose péritonéale. Il s'agit des chimiothérapies intrapéritonéale adjuvante utilisée surtout en Amérique du Nord, hyperthermique intrapéritonéale (CHIP) et intrapéritonéale pressurisée en aérosols (PIPAC). Dans cet article, nous reprenons les données de la littérature sur chacune de ces trois approches thérapeutiques et proposons des algorithmes décisionnels selon la situation clinique des patientes traitées pour un cancer de l'ovaire : au diagnostic, récidive platine-sensible et platine-résistante.

Width of margins in phyllodes tumors of the breast: the controversy drags on?-a systematic review and meta-analysis.

PURPOSE: Phyllodes tumors (PT) of the breast are rare fibroepithelial neoplasms. Information is controversial in the literature regarding to the optimal surgical management. Most studies suggested margins of at least 10 mm while some recent studies suggested narrower margins without an increased risk of local recurrences (LR) and distant metastases (DM). The objective of this systematic review was to identify and compare studies that assessed these different practices. METHODS: A systematic review was performed through five databases up to April 2019. Studies exploring the association between the width of margins, subtypes of PT, and the LR and DM rates were considered for inclusion. A statistical model for analyzing sparse data and rare events was used. RESULTS: Thirteen studies met eligibility criteria and were selected. Considering a threshold of 10 mm (margins < 10 vs margins ≥ 10 mm), the 5-year incidence rate of LR was estimated to be 5.22 vs. 3.63 (diff. -1.59) per 100 person-years for benign PT, 9.60 vs. 7.33 (diff. -2.27) for borderline PT, and 28.58 vs. 21.84 (diff. -6.74) for malignant PT. For DM, it was estimated to be 0.88 vs. 0.86 (diff. -0.02) for benign PT, 1.61 vs. 1.74 (diff. 0.13) for borderline PT, and 4.80 vs 5.18 (diff. 0.38) for malignant PT. The data for a threshold of 1 mm were not sufficient to draw any conclusions. CONCLUSION: Irrespective of tumor grade, we found that DM was a rarer event than LR. Malignant PT had the highest incidence rate of LR and DM. This meta-analysis found a clear association between width of margins and LR rates. Whatever the tumor grade, surgical margins ≥ 10 mm guaranteed a lower risk of LR than margins < 10 mm. On the other hand, the width of margin did not influence the apparition of DM.

Histopathologic Validation of the Sentinel Node Technique for Early-Stage Cervical Cancer Patients.

BACKGROUND: The sentinel lymph node (SLN) biopsy may be an alternative to systematic lymphadenectomy in early cervical cancer. The SLN biopsy is less morbid and has been shown to have high sensitivity for metastasis detection. However, the sensitivity of the SLN technique might be overevaluated because SLNs are examined with ultra-staging, and non-sentinel nodes usually are examined only with routine techniques. This study aimed to validate the negative predictive value (NPV) of the SLN technique by the ultra-staging of SLNs and non-sentinel nodes (NSLNs). METHODS: The SENTICOL 1 study data published in 2011 were used. All nodes (i.e., SLNs and NSLNs) were secondarily subjected to ultra-staging. The ultra-staging consisted of sectioning every 200 µm, in addition to immunohistochemistry. Moreover, the positive slides and 10% of the negative slides were reviewed. RESULTS: The study enrolled 139 patients, and SLNs were detected in 136 (97.8%) of these patiets. Bilateral SLNs were detected in 104 (76.5%) of the 136 patients. A total of 2056 NSLNs were identified (median, 13 NSLNs per patient; range 1-54). Of the 136 patients with SLNs, 23 were shown to have positive SLNs after serial sectioning and immunohistochemical staining. The NSLNs were metastatic in six patients. In the case of bilateral SLN detection, the NPV was 100%, with no false-negatives (FNs). CONCLUSIONS: The pelvic SLN technique is safe and trustworthy for determining the nodal status of patients with early-stage cervical cancer. In the case of optimal mapping with bilateral detection, the NPV was found to be 100%.

[Equity of care in gynecology-obstetrics for the deaf and hard of hearing†: issues]. / Équité des soins en gynécologie-obstétrique pour les personnes sourdes et malentendantes†: enjeux.

The deaf and hard of hearing population suffers from difficulties in accessing the health care system due to communication barriers with health care and administrative personnel who are often insufficiently trained in deafness issues. Gynecology-obstetrics consultations represent a gateway to the health system. Since 2011, there is a gynecology and obstetrics consultation dedicated to deaf people at the CHUV. This article presents the means of communication support put in place within the context of this specific consultation as well as the experience of a group of patients. Awareness of deafness among all staff in contact with patients as well as the use of professional interpreters are the key elements of care that respects the needs and rights of deaf people.

La population sourde et malentendante souffre de difficultés d'accès au système de santé en raison de barrières de communication avec le personnel soignant et administratif, souvent insuffisamment formé aux enjeux de la surdité. Les consultations de gynécologie-obstétrique représentent une porte d'entrée dans le système de santé. Depuis 2011, une consultation de gynécologie-obstétrique dédiée aux personnes sourdes existe au CHUV. Cet article présente les moyens d'aide à la communication mis en place dans le cadre de cette consultation spécialisée ainsi que le vécu d'un collectif de patientes. Une sensibilisation à la surdité de l'ensemble du personnel au contact des patient·e·s ainsi que la sollicitation d'interprètes professionnel·le·s sont les piliers d'une prise en charge respectueuse des besoins et des droits des personnes sourdes.

Pre-operative surgical algorithm: sentinel lymph node biopsy as predictor of parametrial involvement in early-stage cervical cancer.

INTRODUCTION: Radical hysterectomy is the gold standard in the management of early-stage cervical cancer. Parametrectomy aims to remove occult disease but is associated with significant surgical morbidity. Avoiding unnecessary parametrectomy in a subset of patients at low risk of parametrial involvement may decrease the incidence of such morbidity. The purpose of this study was to identify patients at low risk of parametrial involvement in early-stage cervical cancer potentially eligible for less radical surgery based on pre-operative criteria and sentinel lymph node (SLN) status. METHODS: We performed an ancillary analysis of data from two prospective trials on sentinel node biopsy for cervical cancer (SENTICOL I and II). Patients with International Federation of Gynecology and Obstetrics (FIGO) IA-IIA cervical cancer who underwent primary radical surgery and bilateral SLN mapping were identified between 2005 and 2012 from 25 French oncologic centers. Patients who underwent pre-operative brachytherapy or did not undergo radical surgery (simple trachelectomy, simple hysterectomy, or lymph node staging only) were excluded. RESULTS: Of 174 patients who fullfiled the inclusion criteria, 9 patients (5.2%) had parametrial involvement and 24 patients (13.8%) had positive SLN. Most patients had 2018 FIGO stage IB1 disease (86.1%) and squamous cell carcinomas (68.9%). Parametrial involvement was significantly associated with tumor size ≥20 mm on pelvic magnetic resonance imaging (MRI) (adjusted odds ratio (ORa) 9.30, 95% CI 1.71 to 50.57, p=0.01) and micrometastic or macrometastatic SLN (ORa 8.98, 95% CI 1.59 to 50.84, p=0.01). Of 114 patients with tumors <20 mm on pre-operative MRI and negative SLN after ultrastaging, only one patient had parametrial involvement (0.9%). By triaging patients with both of these criteria in a two-step surgical procedure, unjustified and contra-indicated radical hysterectomy would have been avoided in 65.5% and 8.6% of cases, respectively. CONCLUSIONS: Less radical surgery may be an option for patients with bilateral negative SLN after ultrastaging and tumors <20 mm. SLN status should be integrated into the decision-making process for tailored surgery in early-stage cervical cancer.

European Society of Gynaecological Oncology quality indicators for surgical treatment of cervical cancer.

BACKGROUND: Optimizing and ensuring the quality of surgical care is essential to improve the management and outcome of patients with cervical cancer.To develop a list of quality indicators for surgical treatment of cervical cancer that can be used to audit and improve clinical practice. METHODS: Quality indicators were developed using a four-step evaluation process that included a systematic literature search to identify potential quality indicators, in-person meetings of an ad hoc group of international experts, an internal validation process, and external review by a large panel of European clinicians and patient representatives. RESULTS: Fifteen structural, process, and outcome indicators were selected. Using a structured format, each quality indicator has a description specifying what the indicator is measuring. Measurability specifications are also detailed to define how the indicator will be measured in practice. Each indicator has a target which gives practitioners and health administrators a quantitative basis for improving care and organizational processes. DISCUSSION: Implementation of institutional quality assurance programs can improve quality of care, even in high-volume centers. This set of quality indicators from the European Society of Gynaecological Cancer may be a major instrument to improve the quality of surgical treatment of cervical cancer.

[Is there still a space for the vaginal examination in the gynecological consultation ?] / Y a-t-il encore une place pour l'examen vaginal en consultation gynécologique ?

The vaginal examination is too often part of the routine in periodic gynecological consultations. However, its performance as a screening examination for gynecological diseases such as cancers and infections is poor when performed in the asymptomatic patient. It is appropriate for cervical cancer screening every 3 years from the age of 21. Moreover, the intrusive nature of the vaginal examination, which is sometimes experienced as traumatic by patients, encourages the targeting of indications for its practice. Fear of this examination may also result in avoidance of care. The gynecological consultation is a privileged setting for screening for sexual risk taking or domestic violence, but also for exploring overall sexual health and promoting women's health.

L'examen vaginal est trop souvent ancré dans la routine des consultations périodiques en gynécologie. Or, sa performance comme examen de dépistage des maladies gynécologiques telles que cancers et infections est mauvaise lorsqu'il est effectué chez la patiente asymptomatique. Il est justifié tous les 3 ans à partir de 21 ans dans le cadre du dépistage du cancer du col utérin. De plus, le caractère intrusif de l'examen vaginal parfois vécu comme traumatisant par les patientes incite à cibler les indications à sa pratique. La crainte de cet examen peut en outre se manifester par un évitement des soins. La consultation gynécologique est un espace privilégié pour dépister des prises de risque sur le plan sexuel ou des violences domestiques, mais aussi pour l'exploration de la santé sexuelle globale et la promotion de la santé des femmes.

[Treatment of early cervical cancer : Back to the future]. / Traitement du cancer débutant du col de l'utérus : retour vers le future.

The treatment of the early-stage cervical cancer is surgical. In the last ten years we have seen a surgical de-escalation and the development of new techniques such as the sentinel node biopsy. In 2018, absolutely against the trend, the study published in the New England Journal of Medicine by Pedro Ramirez upset the world of gynecologic-oncologists by demonstrating that the open approach is superior to the minimally invasive technique in the surgical management of these cancers. A long debate arose after the publication of this article, which remains the only prospective randomized study published to date on the subject. We therefore must take a step back and return to open surgery in the treatment of early-stage cervical cancer.

Le traitement du cancer débutant du col de l'utérus est la chirurgie. Ces dix dernières années, on a assisté à une désescalade chirurgicale et au développement de nouvelles techniques comme celle du ganglion sentinelle. En 2018, en opposition avec l'évolution actuelle, l'étude publiée dans The New England Journal of Medicine par Pedro Ramirez a bouleversé le monde des gynéco-oncologues en démontrant que la chirurgie ouverte (laparotomie) est supérieure à celle mini-invasive dans la prise en charge chirurgicale de ces cancers. Un long débat est né après la publication de cet article qui reste la seule étude prospective randomisée publiée jusqu'à maintenant sur le sujet. Cependant, actuellement, il est donc impératif de faire un pas en arrière et de revenir à la chirurgie ouverte pour le traitement du cancer débutant du col de l'utérus.

A Phase I/II trial comparing autologous dendritic cell vaccine pulsed either with personalized peptides (PEP-DC) or with tumor lysate (OC-DC) in patients with advanced high-grade ovarian serous carcinoma.

BACKGROUND: Most ovarian cancer patients are diagnosed at a late stage with 85% of them relapsing after surgery and standard chemotherapy; for this reason, new treatments are urgently needed. Ovarian cancer has become a candidate for immunotherapy by reason of their expression of shared tumor-associated antigens (TAAs) and private mutated neoantigens (NeoAgs) and the recognition of the tumor by the immune system. Additionally, the presence of intraepithelial tumor infiltrating lymphocytes (TILs) is associated with improved progression-free and overall survival of patients with ovarian cancer. The aim of active immunotherapy, including vaccination, is to generate a new anti-tumor response and amplify an existing immune response. Recently developed NeoAgs-based cancer vaccines have the advantage of being more tumor specific, reducing the potential for immunological tolerance, and inducing robust immunogenicity. METHODS: We propose a randomized phase I/II study in patients with advanced ovarian cancer to compare the immunogenicity and to assess safety and feasibility of two personalized DC vaccines. After standard of care surgery and chemotherapy, patients will receive either a novel vaccine consisting of autologous DCs pulsed with up to ten peptides (PEP-DC), selected using an agnostic, yet personalized, epitope discovery algorithm, or a sequential combination of a DC vaccine loaded with autologous oxidized tumor lysate (OC-DC) prior to an equivalent PEP-DC vaccine. All vaccines will be administered in combination with low-dose cyclophosphamide. This study is the first attempt to compare the two approaches and to use NeoAgs-based vaccines in ovarian cancer in the adjuvant setting. DISCUSSION: The proposed treatment takes advantage of the beneficial effects of pre-treatment with OC-DC prior to PEP-DC vaccination, prompting immune response induction against a wide range of patient-specific antigens, and amplification of pre-existing NeoAgs-specific T cell clones. Trial registration This trial is already approved by Swissmedic (Ref.: 2019TpP1004) and will be registered at http://www.clinicaltrials.gov before enrollment opens.