To compare the accuracy of five major risk stratification systems (RSS) in classifying the risk of recurrence and nodal metastases in early-stage endometrial cancer (EC).
Data of 553 patients with ...early-stage EC were abstracted from a prospective multicentre database between January 2001 and December 2012. The following RSS were identified in a PubMed literature search and included the Post Operative Radiation Therapy in Endometrial Carcinoma (PORTEC-1), the Gynecologic Oncology Group (GOG)-99, the Survival effect of para-aortic lymphadenectomy (SEPAL), the ESMO and the ESMO-modified classifications. The accuracy of each RSS was evaluated in terms of recurrence-free survival (RFS) and nodal metastases according to discrimination.
Overall, the ESMO -modified RSS provided the highest discrimination for both RFS and for nodal metastases with a concordance index (C-index) of 0.73 (95% CI, 0.70-0.76) and an area under the curve (AUC) of 0.80 (0.78-0.72), respectively. The other RSS performed as follows: the PORTEC1, GOG-99, SEPAL, ESMO classifications gave a C-index of 0.68 (0.66-0.70), 0.65 (0.63-0.67), 0.66 (0.63-0.69), 0.71 (0.68-0.74), respectively, for RFS and an AUC of 0.69 (0.66-0.72), 0.69 (0.67-0.71), 0.68 (0.66-0.70), 0.70 (0.68-0.72), respectively, for node metastases.
None of the five major RSS showed high accuracy in stratifying the risk of recurrence or nodal metastases in patients with early-stage EC, although the ESMO-modified classification emerged as having the highest power of discrimination for both parameters. Therefore, there is a need to revisit existing RSS using additional tools such as biological markers to better stratify risk for these patients.
Abstract
STUDY QUESTION
Could anogenital distance (AGD) be a non-invasive marker of endometriosis and correlated to the American Society for Reproductive Medicine revised score (r-ASRM) and ENZIAN ...classifications?
SUMMARY ANSWER
Surgically and histologically proven endometriosis is associated with a short AGD in women of reproductive age but not correlated either to the severity or to the location of the disease.
WHAT IS KNOWN ALREADY
AGD is a marker of intrauterine androgen exposure and exposure to oestrogen-like chemicals such as phthalates. Moreover, exposure to endocrine disruptors, such as organochlorine chemicals, is associated with endometriosis. It has been suggested that a short AGD in women is associated with an increased risk of endometriosis based on clinical and ultrasound exams.
STUDY DESIGN, SIZE, DURATION
A prospective cohort study was conducted from January 2018 to June 2019 in a tertiary-care centre including 168 adult women undergoing pelvic surgery.
PARTICIPANTS/MATERIALS, SETTING, METHODS
Of the 168 women included, 98 patients had endometriosis (endometriosis group) and 70 did not (non-endometriosis group). An operator (not the surgeon) measured the distance from the clitoral surface to the anus (AGD-AC) and from the posterior fourchette to the anus (AGD-AF) before surgery using a millimetre accuracy ruler. Endometriosis was diagnosed on exploration of the abdominopelvic cavity, and the r-ASRM and ENZIAN scores were calculated. All removed tissues underwent pathological examination.
MAIN RESULTS AND THE ROLE OF CHANCE
Mean (±SD) AGD-AF measurements were 21.5 mm (±6.4) and 32.3 mm (±8.1), and average AGD-AC measurements were 100.9 mm (±20.6) and 83.8 mm (±12.9) in the endometriosis and non-endometriosis groups (P < 0.001), respectively. Mean AGD-AF and AGD-AC measurements were not related to r-ASRM stage (P = 0.73 and 0.80, respectively) or ENZIAN score (P = 0.62 and 0.21, respectively). AGD-AF had a better predictive value than AGD-AC for discriminating the presence of endometriosis (AUC = 0.840 (95% CI 0.782–0.898) and 0.756 (95% CI 0.684–0.828)), respectively. For AGD-AF, an optimal cut-off of 20 mm had a specificity of 0.986 (95% CI 0.923–0.999), sensitivity of 0.306 (95% CI 26.1–31.6) and positive predictive value of 0.969 (95% CI 0.826–0.998). In multivariable analysis, the diagnosis of endometriosis was the only variable independently associated with the AGD-AF (β = −9.66 mm 95% CI −12.20–−7.12), P < 0.001).
LIMITATIONS, REASONS FOR CAUTION
The sample size was relatively small with a high proportion of patients with colorectal endometriosis reflecting the activity of an expert centre. Furthermore, we did not include adolescents and the AGD-AF measurement could be particularly relevant in this population.
WIDER IMPLICATIONS OF THE FINDINGS
The measurement of AGD could be a useful non-invasive tool to predict endometriosis. This could be especially relevant for adolescents and virgin women to avoid diagnostic laparoscopy and empiric treatment.
STUDY FUNDING/COMPETING INTEREST(S)
None.
Vulvar cancer is a rare pathology affecting mainly elderly women. This study aims to evaluate the impact of age on tumor size in vulvar cancer.
This was a multicenter retrospective observational ...study carried out between January 1, 1998, and December 31, 2020, in patients operated on for vulvar cancer. Univariate analysis was performed according to patients' age ≥ or <65 years. Factors associated with tumor size found to be significant according to age were then included in a multiple linear regression model.
Of the 382 patients included, there were 133 patients aged <65 years and 249 ≥ 65 years. Radical total vulvectomy surgeries were more frequently performed in women ≥65 years (n = 72 (28.9 %) versus n = 20 (15 %); p = 0.004). The median histological tumor size and interquartile range was 20 mm 13–29 in the <65 years and 30 mm 15–42 in patients ≥65 years (p = 0.001). Multiple linear regression showed that age ≥65 years had a regression coefficient of 7.15 95 % CI 2.32; 11.99 (p = 0.004), constituting a risk factor for larger histological tumour size. Patients aged ≥65 years old had a higher early complication rate (n = 150 (62 %) versus n = 56 (42.7 %), p = 0.001). They also had a greater risk of recurrence (HR = 1.89 (95%CI (1.24–2.89)), p = 0.003) with a worse overall survival (HR = 5.64 (95%CI (1.70–18.68)), p = 0.005).
Age is a risk factor for larger tumor size, leading to more radical surgery and a greater risk of complications in already fragile patients, with a greater risk of recurrence and an impact on overall survival.
Abstract
STUDY QUESTION
Could the anogenital distance (AGD) as assessed by MRI (MRI-AGD) be a diagnostic tool for endometriosis?
SUMMARY ANSWER
A short MRI-AGD is a strong diagnostic marker of ...endometriosis.
WHAT IS KNOWN ALREADY
A short clinically assessed AGD (C-AGD) is associated with the presence of endometriosis.
STUDY DESIGN, SIZE, DURATION
This study is a re-analysis of previously published data from a case–control study.
PARTICIPANTS/MATERIALS, SETTING, METHODS
Women undergoing pelvic surgery from January 2018 to June 2019 and who had a preoperative pelvic MRI were included. C-AGD was measured at the beginning of the surgery by a different operator who was unaware of the endometriosis status. MRI-AGD was measured retrospectively by a senior radiologist who was blinded to the final diagnosis. Two measurements were made: from the posterior wall of the clitoris to the anterior edge of the anal canal (MRI-AGD-AC), and from the posterior wall of the vagina to the anterior edge of the anal canal (MRI-AGD-AF).
MAIN RESULTS AND THE ROLE OF CHANCE
The study compared MRI-AGD of 67 women with endometriosis to 31 without endometriosis (controls). Average MRI-AGD-AF measurements were 13.3 mm (±3.9) and 21.2 mm (±5.4) in the endometriosis and non-endometriosis groups, respectively (P < 10−5). Average MRI-AGD-AC measurements were 40.4 mm (±7.3) and 51.1 mm (±8.6) for the endometriosis and non-endometriosis groups, respectively (P < 10−5). There was no difference of MRI-AGD in women with and without endometrioma (P = 0.21), or digestive involvement (P = 0.26). Moreover, MRI-AGD values were independent of the revised score of the American Society of Reproductive Medicine and the Enzian score. The diagnosis of endometriosis was negatively associated with both the MRI-AGD-AF (β = −7.79, 95% CI (−9.88; −5.71), P < 0.001) and MRI-AGD-AC (β = −9.51 mm, 95% CI (−12.7; 6.24), P < 0.001) in multivariable analysis. Age (β = +0.31 mm, 95% CI (0.09; 0.53), P = 0.006) and BMI (β = +0.44 mm, 95% CI (0.17; 0.72), P = 0.001) were positively associated with the MRI-AGD-AC measurements in multivariable analysis. MRI-AGD-AF had an AUC of 0.869 (95% CI (0.79; 0.95)) and outperformed C-AGD. Using an optimal cut-off of 20 mm for MRI-AGD-AF, a sensitivity of 97.01% and a specificity of 70.97% were noted.
LIMITATIONS, REASONS FOR CAUTION
This was a retrospective analysis and no adolescents had been included.
WIDER IMPLICATIONS OF THE FINDINGS
This study is consistent with previous works associating a short C-AGD with endometriosis and the absence of correlation with the disease phenotype. MRI-AGD is more accurate than C-AGD in this setting and could be evaluated in the MRI examination of patients with suspected endometriosis.
STUDY FUNDING/COMPETING INTEREST(S)
N/A.
TRIAL REGISTRATION NUMBER
The protocol was approved by the ‘Groupe Nantais d’Ethique dans le Domaine de la Santé’ and registered under reference 02651077.
In vulvar cancer, it is admitted that tumor-free margin distance is one of the most important element for locoregional control. It is currently recommended to surgically remove the tumor with at ...least an 8 mm tumor-free margin. The aim of this study was to evaluate the impact of tumor-free margin distance on recurrence and survival in vulvar cancer.
From 2005 to 2016, 112 patients surgically treated for a vulvar squamous cell cancer were included in a retrospective multicenter study. Overall, disease-free and metastasis-free survivals were analyzed according to tumor-free margin distance.
Patients were divided into three groups: group 1 (margin <3 mm, n = 47); group 2 (margin ≥3 mm to < 8 mm, n = 48) and group 3 (margin ≥8 mm, n = 17). During the study, 26,8% patients developed recurrence (n = 30) after a median of 8 months (1-69). Analysis of 5-year overall survival, as well as disease-free and metastasis-free survivals, did not reveal a difference between groups. We performed a subgroup analysis in patients with a tumor-free margin <8 mm (group 1 and 2). It showed that histological lesions observed closest to the edge of the specimen were more often invasive or in situ carcinoma lesions in group 1 than in group 2, in which VIN lesions were mainly observed at this location. After re-excision, no patients in group 1 and 50% (n = 2) patients in group 2 developed recurrence.
This study did not reveal a significant impact of tumor-free margin distance on recurrence and survival in vulvar cancer. Moreover, the benefit of re-excision seems stronger when tumor-free margins are positive or very close (<3 mm), cases in which invasive or in situ lesions are often present closest to the edge of the specimen.
Lymphovascular space invasion (LVSI) is one of the most important predictors of nodal involvement and recurrence in early stage endometrial cancer (EC). Despite its demonstrated prognostic value, ...LVSI has not been incorporated into the European Society of Medical Oncology (ESMO) classification. The aim of this prospective multicentre database study is to investigate whether it may improve the accuracy of the ESMO classification in predicting the recurrence risk.
Data of 496 patients with apparent early-stage EC who received primary surgical treatment between January 2001 and December 2012 were abstracted from prospective multicentre database. A modified ESMO classification including six risk groups was created after inclusion of the LVSI status in the ESMO classification. The primary end point was the recurrence accuracy comparison between the ESMO and the modified ESMO classifications with respect to the area under the receiver operating characteristic curve (AUC).
The recurrence rate in the whole population was 16.1%. The median follow-up and recurrence time were 31 (range: 1-152) and 27 (range: 1-134) months, respectively. Considering the ESMO modified classification, the recurrence rates were 8.2% (8 out of 98), 23.1% (15 out of 65), 25.9% (15 out of 58), and 45.1% (28 out of 62) for intermediate risk/LVSI-, intermediate risk/LVSI+, high risk/LVSI-, and high risk/LVSI+, respectively (P<0.001). In the low risk group, LVSI status was not discriminant as only 7.0% (14 out of 213) had LVSI+. The staging accuracy according to AUC criteria for ESMO and ESMO modified classifications were of 0.71 (95% CI: 0.68-0.74) and 0.74 (95% CI: 0.71-0.77), respectively.
The current modified classification could be helpful to better define indications for nodal staging and adjuvant therapy, especially for patients with intermediate risk EC.
Endometriosis-related infertility remains a therapeutic challenge. A burning issue in this field of research is determining whether pre-assisted reproductive technology (ART) surgery may be of some ...benefit in terms of reproductive outcomes. This systematic review and meta-analysis aimed at comparing ongoing pregnancy rates (OPR) and/or live birth rates (LBR) in patients who underwent endometriosis surgery before ART (IVF/ICSI) in comparison with patients who underwent first-line ART (IVF/ICSI). Searches were conducted from January 1990 to June 2021 on PubMed, Embase, and Cochrane Library using the following search terms: endometriosis, surgery, reproductive outcomes, and IVF/ICSI. The primary outcomes were OPR or LBR. A total of 19 studies were included in the meta-analysis. No statistically significant differences in LBR 0.910.63, 1.30; I
= 66%; n = 11, OPR 1.280.66, 2.49; I
= 60%; n = 3, and early pregnancy loss rate 0.880.62, 1.25; I
= 0%; n = 7 per cycle were found when comparing patients who underwent endometriosis surgery before IVF/ICSI and those who did not. After the exclusion of the studies with high risks of bias, the LBR per cycle was significantly reduced in the case of surgical treatment before IVF/ICSI 0.530.33, 0.86; I
= 30%; n = 4. These data urge the clinician to carefully weigh the pros and cons before referring infertile patients with endometriosis to surgery before IVF, highlighting the key role of multidisciplinary referral centers.
To describe strategy and results of fertility preservation (FP) in patients with malignant and borderline ovarian tumors.
Consecutive cohort study of 43 women with malignant or borderline ovarian ...tumors who underwent FP between February 2013 and July 2019.
The study was conducted in national expert center in Tenon University Hospital, Sorbonne University: French ESGO-certified ovarian cancer center and pregnancy-associated cancer network (CALG). Main outcome measure was FP technique proposed by multidisciplinary committee, FP technique used, time after surgery, number of fragments, histology and follicle density (if ovarian tissue freezing), number of expected, retrieved and frozen oocytes (if ovarian stimulation).
Pathological diagnosis was malignant epithelial ovarian tumor in five women (11.6%), rare malignant ovarian tumor in 14 (32.6%), borderline in 24 (55.8%), and mostly unilateral (79.1%) and stage I (76.7%). Mean age at diagnosis was 26.8 ± 6.9 years and mean tumor size 109.7 ± 61 mm. Before FP, mean AFC was 11.0 ± 6.1 and AMH levels were 2.7 ± 4.6 ng/mL. Six ovarian tissue-freezing procedures were performed (offered to 13). Twenty-four procedures of ovarian stimulation and oocyte freezing were performed after surgical treatment for 19 women (offered to 28) with a median interval of 188 days. The mean number of mature oocytes retrieved per stimulation was 12.4 ± 12.8. At least 10 mature oocytes were frozen for 52.6% of the women. No FP was offered to five women.
Oocyte and ovarian tissue cryopreservation should be offered to patients with malignant and borderline ovarian tumors. More data are needed to confirm ovarian stimulation and ovarian tissue grafting safety.
•The median number of ovarian tissue frozen fragments was 22 per patient•In mature oocyte vitrification after ovarian stimulation ten or more frozen oocytes were obtained in 55.6% patients•Preoperative fertility preservation consultations increased from 0% in 2013 to 67% in 2019•Only 28.6% of the patients declined ovarian stimulation for oocyte cryopreservation
To compare first-line surgery with first-line assisted reproductive techniques (ART) in infertile women with deep infiltrating endometriosis (DIE) without colorectal involvement.
A retrospective ...comparative cohort study with a propensity-score matching analysis, in four tertiary-care referral centers. The population was infertile women with DIE without colorectal involvement. The patients were managed either by first-line surgery followed by spontaneous conception attempts and/or ART, or by first-line ART. 284 patients were extracted from the databases. After matching, 92 patients were compared in each group. Clinical pregnancy rates (PR) and live-birth rates (LBR) were the primary outcomes, and cumulative pregnancy rate (CPR) and cumulative live birth rate (CLBR) were the secondary outcomes.
The mean number of IVF-ICSI cycles per patient was 1.4, with a significant difference between the groups: 1.6 in the first-line ART group and 1.2 in the first-line surgery group (p = 0.006). The PR was significantly higher in the first-line surgery group (72 % vs 35 %; p < 0.001). In the first-line surgery group, non-ART pregnancies occurred in 18 % (17/92) while no non-ART pregnancies was noted in the first-line ART group. The LBR was significantly higher in the first-line surgery group (61 % vs 24 %; p < 0.001). After ART, the CPR were 72 % (47/67) in the first-line surgery group, and 35 % (32/92) in the first-line ART group (p < 0.001).
After matching, our results support that first-line surgery offer higher pregnancy and live-birth rates than first-line ART in patients with DIE without colorectal involvement.
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