The Impact of Conservative Surgical Treatment of Adenomyosis on Fertility and Perinatal Outcomes.

Adenomyosis is a benign condition commonly encountered in patients with infertility. While the definitive surgical management is hysterectomy, conservative surgical management is gaining attention in patients desiring future fertility. This review explores whether the surgical treatment of adenomyosis affects fertility outcomes for patients trying to conceive. The PubMed and Medline databases were searched using the keywords: "adenomyosis", "surgery", "radiofrequency", "infertility", "pregnancy", "sterility", "conception", "miscarriage", and "endometrial receptivity". Abstracts were screened, and relevant articles were selected for review. This review reveals that surgery appears to improve fertility outcomes with or without medical therapy; however, the risk of uterine rupture remains high and the best technique to reduce this risk is still not known. More studies are needed to formulate the best surgical approach for preserving fertility in treating adenomyosis and to establish standardized guidelines.

Tertiary prevention strategies for micrometastatic lymph node cervical cancer: A systematic review and a prototype of an adapted model of care.

PURPOSE: We found a need for balancing the application of clinical guidelines and tailored approaches to follow-up of cervical cancer (CC) patients in the lymph node micrometastatic (MICs) setting. This review aimed to determine the current knowledge of management of MIC-positive CC cases. METHODOLOGY: We addressed prognostic and risk of recurrence monitoring impacts associated with MIC+ cases. The electronic databases for literature and relevant articles were analysed. RESULTS: Fifteen studies, (4882 patients), were included in our systematic review. While the results show that MICs significantly worsen prognosis in early CC. A tertiary prevention algorithm for low volume lymph node disease may stratify follow-up according to the burden of nodal disease and provide data that helps improve follow-up performance. CONCLUSION: MICs worsen prognosis and should be managed as suggested by the algorithm. However, this algorithm must be externally validated. The clinical impact of isolated tumor cells (ITC) remains unclear.

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.

The Present and the Future of Medical Therapies for Adenomyosis: A Narrative Review.

Uterine Adenomyosis is a benign condition characterized by the presence of endometrium-like epithelial and stromal tissue in the myometrium. Several medical treatments have been proposed, but still, no guidelines directing the management of adenomyosis are available. While a hysterectomy is typically regarded as the definitive treatment for adenomyosis, the scarcity of high-quality data leaves patients desiring fertility with limited conservative options. Based on the available data, the levonorgestrel-IUD appears to offer the most favorable outcomes. Other treatments, including GnRH antagonists, dienogest, prolactin, and oxytocin modulators, show promise; however, further data are required to establish their efficacy definitively. Furthermore, there are many emerging therapies that have been developed that seem worthy of consideration in the near future. The aim of this narrative review was to explore the current medical treatments available for adenomyosis and to provide a glimpse of future therapies under assessment. For this scope, we performed a literature search on PubMed and Medline from incept to September 2022 using the keywords: "medical treatment", "non-steroidal anti-inflammatory", "progesterone intrauterine device", "dienogest", "combined oral contraceptives", "gonadotropin releasing hormone agonist", "gonadotropin releasing hormone antagonist", "danazol", "aromatase inhibitors", "ulipristal acetate", "anti-platelet therapy", "dopamine", "oxytocin antagonists", "STAT3", "KRAS", "MAPK", "micro-RNA", "mifepristone", "valproic acid", "levo-tetrahydropalamatine", and "andrographolide". The search was limited to articles in English, with subsequent screening of abstracts. Abstracts were screened to select relevant studies.

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.

Adenomyosis: An Updated Review on Diagnosis and Classification.

Adenomyosis is a commonly diagnosed benign condition characterized by the presence of ectopic endometrial glands within the underlying myometrium. The most common presenting signs and symptoms are abnormal uterine bleeding, chronic pelvic pain, and infertility. The clinical relevance of this condition is evident in both medical and surgical care. Histopathology and imaging studies are used for the diagnosis and classification of adenomyosis, which are hallmarks of the advancement of our ability to diagnose adenomyosis. Importantly, the diagnosis and classification of adenomyosis lacks standardization due to the nature of imaging techniques, features of adenomyosis, and the clinical spectrum of adenomyosis. We reviewed the literature to summarize the available classification systems for adenomyosis and highlight the different imaging approaches and histologic criteria used in diagnosis. Despite the high prevalence of the disease, there is no clear consensus on one classification system. We provide a review of some of the classification systems available and discuss their strengths and limitations.

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.

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.

Ruptured ectopic pregnancy as complete hydatidiform mole: Case report and review of the literature.

Usually, a hydatidiform mole (HM) develops inside the uterus. The occurrence of HM in ruptured tubal pregnancy is exceptional. Cases reported in the literature are scarce. In this article, a case of haemoperitoneum secondary to a ruptured fallopian tube by a complete mole is reported. A 50-year-old gravida 2, para 1 was admitted to the emergency department for acute abdominal pain. After the clinical examination, an abdominal sonography and CT scan were done, revealing the presence of an adnexal left mass associated with an important haemoperitoneum. A urine pregnancy test was done and was positive, indicating an immediate laparoscopic exploration. The laparoscopy revealed a haemoperitoneum secondary to a ruptured tubal mass. The pathological exam concluded a complete hydatidiform mole (CHM) invading the wall of the fallopian tube. Any acute abdominal pain in a potentially pregnant woman imposes first the routine realization of a pregnancy test. The occurrence of CHM in a ruptured fallopian tube is particularly rare and has exceptionally been diagnosed before the laparoscopic exploration.

Endometriosis and Infertility: Prognostic Value of #Enzian Classification Compared to rASRM and EFI Score.

This study's objective was to compare the predictive validity of the three most utilized classification scores for endometriosis, #Enzian, EFI, and rASRM, in achieving a spontaneous pregnancy or pregnancy via assisted reproductive technology (ART) after surgery for endometriosis. The monocentric retrospective study was carried out from January 2012 to December 2021 at the gynaecology department of the cantonal hospital of Fribourg. Patients consulting for infertility and operated on for endometriosis with histological confirmation were included. The predictive value of #Enzian, rASRM, and EFI was evaluated and compared concerning the prediction of fertility after surgery, both spontaneous and ART, during the following 12 months. A total of 58 women (mean age 33.1 ± 4.57 years) were included. Overall, 30 women achieved a pregnancy, seven spontaneously. Among all women who achieved a pregnancy, there was a lower prevalence of rASRM stage III−IV (16.67% vs. 39.29%, p = 0.054). Women achieving a pregnancy had a significantly higher EFI score than others (p < 0.05). No significant differences were observed concerning the #Enzian score. In conclusion, the revised #Enzian score is not correlated with pregnancy achievement; EFI score is the only score significantly associated with the pregnancy outcome in women affected by endometriosis.

Surgical management of patients with advanced ovarian cancer: Results of a French National Survey.

INTRODUCTION: Desire to homogenize advanced stage ovarian cancer management has led to a debate on the need to centralize cares. The aim was to assess current practices to compare them with centralization motivation and to overview possible perspectives of evolution. METHODS: An anonymous questionnaire of 57 questions has been submitted from August 2021 to October 2021 to members of French gynecological oncological surgical societies. Questions encompassed all aspects of ovarian cancer surgical management, including institutions, technics, indications, and outcomes. RESULTS: Of the 40 responses, 77.5% managed less than 20 cases by themselves, but 67.5% practiced in institution managing more than 30 cases annually. Since the LION trial results' publication, 95% of practitioners have evolved their lymphadenectomy indications. More than 10% of surgery needed digestive resection for 90% of practitioners. Digestive resections rate was significantly higher for practitioners managing more than 20 cases (p<0.01), but it was not for institutions managing more than 30 cases annually (p=0,07). Surgeons performing more than 20 ovarian cancers annually reported less severe complications (p=0.04) compared to low-volume surgeons independently of institution volume. For more than a quarter of the practitioners, less than half of the patients can benefit from the enhanced recovery after surgery program despite benefits of such care. CONCLUSION: Our survey provides an overview of French practices in ovarian cancer management. This survey seems to confirm that minimum volume thresholds could lead to better outcomes. It also underlines that individual performances are as valuable as center volume.

Estimation risk of lymph nodal invasion in patients with early-stage cervical cancer: Cervical cancer application.

Introduction: Lymph node status is a major prognostic factor in early-stage cervical cancer. Predicting the risk of lymph node metastasis is essential for optimal therapeutic management. The aim of the study was to develop a web-based application to predict the risk of lymph node metastasis in patients with early-stage (IA1 with positive lymph vascular space invasion, IA2 and IB1) cervical cancer. Materials and methods: We performed a secondary analysis of data from two prospective multicenter trials, Senticol 1 and 2 pooled together in the training dataset. The histological risk factors were included in a multivariate logistic regression model in order to determine the most suitable prediction model. An internal validation of the chosen prediction model was then carried out by a cross validation of the 'leave one out cross validation' type. The prediction model was implemented in an interactive online application of the 'Shinyapp' type. Finally, an external validation was performed with a retrospective cohort from L'Hôtel-Dieu de Québec in Canada. Results: Three hundred twenty-one patients participating in Senticol 1 and 2 were included in our training analysis. Among these patients, 280 did not present lymph node invasion (87.2%), 13 presented isolated tumor cells (4%), 11 presented micrometastases (3.4%) and 17 macrometastases (5.3%). Tumor size, presence of lymph-vascular space invasion and stromal invasion were included in the prediction model. The Receiver Operating Characteristic (ROC) Curve from this model had an area under the curve (AUC) of 0.79 (95% CI [0.69- 0.90]). The AUC from the cross validation was 0.65. The external validation on the Canadian cohort confirmed a good discrimination of the model with an AUC of 0.83. Discussion: This is the first study of a prediction score for lymph node involvement in early-stage cervical cancer that includes internal and external validation. The web application is a simple, practical, and modern method of using this prediction score to assist in clinical management.

Lymph Node Involvement in Early-Stage Cervical Cancer: Is Lymphangiogenesis a Risk Factor? Results from the MICROCOL Study.

Background: In patients with cervical cancer, the presence of tumoral lymph-vascular space invasion (LVSI) is the main risk factor for pelvic lymph node metastasis (PLNM). The objective of this study was to evaluate the presence of several markers of lymphangiogenesis in early-stage cervical cancer and their correlation with PLNM and tumoral recurrence. Materials and Methods: Seventy-five patients with early-stage cervical carcinoma underwent sentinel lymph node (SLN) sampling in association with complete pelvic lymph node dissection. Primary tumors were stained with the following markers: Ki67, D2-40, CD31 and VEGF-C. A 3-year follow-up was performed to evaluate the disease-free survival. Results: Overall, 14 patients (18.6%) had PLNM. Positive LVSI was seen in 29 patients (38.6%). There was a significant correlation between LVSI evidenced by H/E staining and PLNM (p < 0.001). There was no correlation between high Ki67, CD31, D2-40, and VEGF-C staining with PLNM or tumor recurrence. Conclusions: Our data support that lymphatic spread does not require the proliferation of new lymphatic endothelial cells in early-stage cervical cancer. These results emphasize the importance of pre-existing peritumoral lymphatic vessels in the metastatic process in early cervical cancer. None of the markers of lymphangiogenesis and proliferation assessed in this study were predictive of PLNM or recurrence.

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.