Risk prediction and modeling in early stage endometrial cancer

Le développement de nouvelles options thérapeutiques est à l’origine d’un changement de paradigme dans le processus de décision médicale. L'émergence de la médecine individualisée et la complexité croissante des données médicales ont conduit à l'avènement des modèles de prédiction. Pour le cancer de l'endomètre, ces modèles (algorithmes, scores et nomogrammes) ont été développés pour stratifier, estimer et prédire le risque de métastase ganglionnaire et de récidive. Le principal enjeu clinique est d’intégrer ces outils en vu d’optimiser les stratégies de prévention, de diagnostic et de traitement. Nous nous sommes intéressés au risque de récidive et d’envahissement ganglionnaire sur la base d’une analyse en population, puis individuelle. À l’échelle de la population, nous avons proposé : i) un travail de comparaison des principales classifications internationales, ii) une nouvelle classification clinicopathologique reposant sur l’incorporation d’un prédicteur histologique, iii) le développement de scores de stratification du risque. À l’échelle individuelle, nous avons développé : i) une méthodologie de validation externe des modèles prédictifs, point de départ indispensable à leur utilisation en pratique, ii) un nomogramme clinicopathologique spécifique d’envahissement ganglionnaire et son seuil de décision clinique. La modélisation mathématique en cancérologie est susceptible de transformer notre façon d’appréhender les stratégies préventives et curatives dans le cancer de l’endomètre. Les pistes d’optimisation sont multiples et laissent entrevoir la possibilité, dans un avenir proche, d’une application clinique à ces outils.With the abundance of new options in diagnostic and treatment modalities, a shift in the medical decision process for endometrial cancer has been observed. The emergence of individualized medicine and the increasing complexity of available medical data have lead to the development of prediction models. In endometrial cancer, those clinical models (algorithms, nomograms, and risk scoring systems) have been reported, for stratifying and subgrouping patients, with various unanswered questions regarding such things as the optimal surgical staging for lymph node metastasis as well as the assessment of recurrence and survival outcomes. Through this manuscript we developed the question of the risk stratification for recurrence at the population level and the probability of lymph node involvement estimation at an individual level in early stage endometrial cancer. This double approach was adopted with the aim to illustrate the interest of these tools in clinical practice. At the population level, we proposed: i) a comparison of the main international clinicopathological classifications ii) a new clinicopathological classification based on a pathological predictor iii) two risk stratification systems for recurrence and lymph node metastasis. At the individual level we developed: i) a reproducible methodology for external validation of predictive models, ii) a specific clinic pathological nomogram for lymph node metastasis. In the future, the emerging field of molecular or biochemical markers research may substantially improve the predictive approach for preventive and curative strategies in endometrial cancer

Association of the number of sentinel lymph nodes harvested with survival in breast cancer

International audienceAims: In patients with breast cancer, the association between the number of sentinel lymph node (SLN) removed and survival is poorly known. Our objective was to evaluate this association on disease-specific survival (DSS). Methods: Data of 144 517 patients with invasive T1-3M0 breast carcinoma and initial treatment with SLN biopsy were extracted from the SEER database. Univariate and multivariate analyses were performed. Results: The number of SLNs harvested and the completion of axillary lymph node dissection (ALND) were not associated with DSS improvement for patients without metastatic nodes. After adjustment, patients with three SLNs had a better DSS than did other groups (HR of 0.73 CI 95% [0.60e0.88], p 1/4 0.001). This result was mainly driven by the group of patients with one metastatic LN. When patients had two or more metastatic LNs, there was no difference in DSS according to the number of SLNs or to completion of ALND. Conclusions: The number of SLN harvested was associated with DSS. According to DSS, the optimal number of SLNs harvested was three in this large series, thereby calling into question the understaging or undertreatment of SLN biopsy in which only one or two SLNs are harvested but also the therapeutic effect of completion ALND

Surgical outcomes after colorectal surgery for endometriosis: Systematic Review and Meta-Analysis

International audienceObjective: To assess the impact of type of surgery for colorectal endometriosis -rectal shaving, discoid or colorectal segmental resection- on complications and surgical outcomes.Data sources: We performed a systematic review of all English and French language full-text articles addressing surgical management of colorectal endometriosis and compared the postoperative complications according to surgical technique by meta-analysis. The PubMed, Clinical Trials.gov Cochrane Library and Web of Science databases were searched for relevant studies published before March 27, 2020. The search strategy used the following MeSH terms: ("bowel endometriosis" or "colorectal endometriosis") AND ("surgery for endometriosis" or "conservative management" or "radical management" or "colorectal resection" or "shaving" or "full thickness resection" or "disc excision") AND ("treatment", "outcomes", "long term results" and "complications").Methods of study selection: Two authors conducted the literature search and independently screened abstracts for inclusion, with resolution of any difference by three other authors. Studies were included when data on surgical management (shaving, disc excision and/ or segmental resection) were provided and when postoperative outcomes were detailed with at least the number of complications. The risk of bias was assessed according to the Cochrane recommendations.Tabulation, integration, and results: Of the168 full-text articles assessed for eligibility, 60 were included in the qualitative synthesis. Seventeen of these were included in the meta-analysis on rectovaginal fistula, 10 on anastomotic leakage, five on anastomotic stenosis, and nine on voiding dysfunction <30 days. The mean complication rate according to shaving, discoid excision and segmental resection were 2.2%, 9.7% and 9.9%, respectively. Rectal shaving was less associated with rectovaginal fistula than discoid excision (OR=0.19; 95% CI [0.10-0.36], p<0.00001, I2=33%) and segmental colorectal resection (OR=0.26, 95% IC [0.15-0.44], p<0.00001, I2=0%). No difference was found in the occurrence of rectovaginal fistula between discoid excision and segmental colorectal resection (OR=1.07, 95%CI [0.70-1.63], p=0.76, I2=0%). Rectal shaving was less associated with leakage than disc excision (OR=0.22, 95% IC [0.06-0.73], p=0.01, I2=86%). No difference was found in the occurrence of leakage between rectal shaving and segmental colorectal resection (OR=0.32, 95% IC [0.10-1.01], p=0.05, I2=71%) or between disc excision and segmental colorectal resection (OR=0.32, 95% IC [0.30-1.58], p=0.38, I2=0%). Disc excision was less associated with anastomotic stenosis than segmental resection (OR=0.15, 95% IC [0.05-0.48], p=0.001, I2=59%). Disc excision was associated with more voiding dysfunction <30 days than rectal shaving (OR=12.9, 95% IC [1.40-119.34], p=0.02, I2=0%). No difference was found in the occurrence of voiding dysfunction <30 days between segmental resection and rectal shaving (OR=3.05, 95% IC [0.55-16.87], p=0.20, I2=0%) or between segmental colorectal and discoid resection (OR=0.99, 95% IC [0.54-1.85], p=0.99, I2=71%).Conclusion: Colorectal surgery for endometriosis exposes patients to a risk of severe complications such as rectovaginal fistula, anastomotic leakage, anastomotic stenosis and voiding dysfunction. Rectal shaving appears to be less associated with postoperative complications than disc excision and segmental colorectal resection. However, this technique is not suitable in all patients with large bowel infiltration. Compared to segmental colorectal resection, disc excision has several advantages including shorter operating time, shorter hospital stay and lower risk of postoperative bowel stenosis

Diagnostic performance of MR imaging, coloscan and MRI/CT enterography for the diagnosis of pelvic endometriosis: CNGOF-HAS Endometriosis Guidelines.

International audienceDiagnostic performance of MR imaging for the diagnosis of pelvic endometriosis are good. Even if some differences of performances exists according the location considered, the risk of misdiagnosis is lower than 10% for trained teams (NP2). The performance of pelvic MR imaging and surgery are quite similar to diagnose endometrioma (sensitivity and specificity>90%). A negative pelvic MR imaging allows to exclude deep pelvic endometriosis with a performance similar to surgery but a positive MR imaging is less accurate than surgery because of a high number of false positives (23%). Pelvic MR imaging is more sensitive and less specific than ultrasonography for the diagnosis of uterosacral ligament, vagina or recto vaginal septum (NP2). Pelvic ultrasonography is more sensitive than pelvic MR imaging for the diagnosis of colorectal location (NP3). Pelvic MR imaging is a reproducible technique for the diagnosis of pelvic endometriosis (NP3). Regarding, quality criteria of pelvic MR imaging, no data are enough to recommend a specific MR unit, digestive preparation, or a specific moment during the menstrual cycle to realize the examination. Vaginal and/or rectal opacification are options. Most of studies are based a protocol including 3D T2W and 3DT1W sequences. Gadolinium injection is useful to characterize a complex adnexal mass. In clinical routine, slices crossing the kidneys are useful to evaluate the presence of pyelo calic distension. ColoCT is an accurate technique to diagnose pelvic digestive endometriosis (rectosigmoide and iléocaecal) (NP3).Les performances de l’IRM pelvienne pour le diagnostic d’endométriose sont bonnes. Même si des différences existent entre les différentes localisations, le risque de classement à tort est égal ou inférieur à 10 % pour les équipes entraînées (NP2). L’IRM pelvienne peut être considérée comme une technique diagnostique proche de la chirurgie pour le diagnostic d’endométriome ovarien (sensibilité et spécificité supérieures à 90 %). Une IRM pelvienne négative permet d’exclure des lésions d’endométriose pelvienne profonde avec une performance proche de la chirurgie alors qu’une IRM pelvienne positive est moins performante que la chirurgie en raison du nombre de faux positifs d’environ 23 % (NP1). L’IRM pelvienne est plus sensible et moins spécifique que l’échographie endovaginale pour le diagnostic des ligaments utérosacrés, du vagin, et de la cloison rectovaginale (NP2). L’échographie pelvienne est plus sensible que l’IRM pelvienne pour le diagnostic de l’endométriose du rectosigmoide (NP3). L’IRM pelvienne est une technique reproductible pour le diagnostic d’endométriose pelvienne (NP3). Concernant les critères de qualité de l’IRM pelvienne, aucune donnée suffisante dans la littérature ne permet de recommander une machine spécifique, une préparation préalable ou des conditions de réalisation spécifique au cours du cycle. L’opacification du vagin et/ou du rectum est une option. La plupart des études se basent sur des séquences multi planaires en T2 et T1 pour faire le diagnostic d’endométriose pelvienne. L’injection de gadolinium est utile pour caractériser une masse annexielle complexe. Les recommandations de bonne pratique sont de disposer de coupes passant par les reins et de faire une acquisition à vessie semi pleine pour ne pas gêner l’interprétation (accord d’expert). Le ColoCT est une technique performante pour le diagnostic d’endométriose pelvienne digestive du rectosigmoide et iléocaecale (NP3)

Voiding Dysfunction after Colorectal Surgery for Endometriosis: A Systematic Review and Meta-analysis

International audienceObjective: Surgical management of deep endometriosis is associated with a high incidence of lower urinary tract dysfunction. The aim of the current systematic review and meta-analysis was to assess the rates of voiding dysfunction according to colorectal shaving, discoid excision, and segmental resection for deep endometriosis.Data sources: We performed a systematic review using bibliographic citations from PubMed, Clinical Trials.gov, Embase, Cochrane Library, and Web of Science databases. Medical Subject Headings terms for colorectal endometriosis and voiding dysfunction were combined and restricted to the French and English languages. The final search was performed on August 28, 2019. The outcome measured was the occurrence of postoperative voiding dysfunction.Methods of study selection: Study Quality Assessment Tools were used to assess the quality of included studies. Studies rated as good and fair were included. Two reviewers independently assessed the quality of each included study, discrepancies were discussed; if consensus was not reached, a third reviewer was consulted.Tabulation, integration and results: Out of 201 relevant published reports, 51 studies were ultimately reviewed systematically and 13 were included in the meta-analysis. Rectal shaving was statistically less associated with postoperative voiding dysfunction than segmental colorectal resection (Odds ratio [OR] 0.34; 95% confidence intervals [CI], 0.18-0.63; I2 = 0%; p 1 month than segmental colorectal resection (OR 0.3; 95% CI, 0.14-0.66; I2 = 0%; p = .003). This outcome was no longer significant when comparing discoid excision and segmental colorectal resection (OR 0.72; 95% CI, 0.4-1.31; I2 = 63%; p = .28).Conclusion: Colorectal surgery for endometriosis has a significant impact on urinary function regardless of the technique. However, rectal shaving causes less postoperative voiding dysfunction than discoid excision or segmental resection

PD-L1 expression with QR1 and E1L3N antibodies according to histological ovarian cancer subtype: A series of 232 cases

International audienceTherapeutic strategies for epithelial ovarian cancers are evolving with the advent of immunotherapy, such as PD-L1 inhibitors, with encouraging results. However, little data are available on PDL-1 expression in ovarian cancers. Thus, we set out to determine the PD-L1 expression according to histological subtype. We evaluated the expression of two PD-L1 clones-QR1 and E1L3N-with two scores, one based on the percentage of labeled tumor cells (tumor proportion score, TPS) and the other on labeled immune cells (combined proportion score, CPS) in a consecutive retrospective series of 232 ovarian cancers. PD-L1 expression was more frequent in high grade serous carcinoma (27.5% with E1L3N clone and 41.5% with QR1 clone), grade 3 endometrioid carcinoma (25% with E1L3N clone and 50% with QR1 clone), and clear-cell carcinomas (27.3% with E1L3N clone and 29.6% with QR1 clone) than other histological subtypes with CPS score. Using the CPS score, 17% of cases were labeled with E1L3N vs 28% with QR1. Using the TPS score, 14% of cases were positive to E1L3N vs 17% for QR1. For TPS and CPS, respectively, 77% and 78% of the QR1 cases were concordant with E1L3N for the thresholds of 1%. Overall and progression-free survival between PD-L1 positive and PD-L1 negative patients were not different across all histological types, and each subtype in particular for serous carcinomas expressing PD-L1. Expression of PD-L1 is relatively uncommon in epithelium ovarian tumors. When positive, usually <10% of tumor cells are labeled. QR1 clone and CPS appear the best tools to evaluate PD-L1 expression

Appropriate surgical management of ovarian endometrioma: excision or drainage?

International audienceEndometriosis negatively impacts the lives of countless women around the world. When medical management fails to improve quality of life often women are left making a decision whether or not to proceed with surgery. With endometriomas, patient's surgical options include complete surgical removal or drainage via laparoscopy. Here, we review the literature to discuss both techniques, excision and drainage of endometriomas, and what the research supports for endometrioma management

A narrative review of functional outcomes following nerve-sparing surgery for deeply infiltrating endometriosis

International audienceEndometriosis negatively impacts the lives of countless women around the world. When medical management fails to improve the quality of life for women with either previously confirmed or suspected endometriosis often a decision must be made whether or not to proceed with surgery. When deeply infiltrating disease is diagnosed either clinically or by imaging studies often medical management alone will not suffice without excisional surgery. Surgery for endometriosis, especially deeply infiltrating disease, is not without risks. Aside from common risks of surgery endometriosis may also involve pelvic nerves, which can be hard to recognize to the untrained eye. Identification of pelvic nerves commonly encountered during endometriosis surgery is paramount to avoid inadvertent injury to optimize function outcomes. Injury to pelvic nerves can lead to urinary retention, constipation, sexual dysfunction, and refractory pain. However, nerve-sparing surgery for endometriosis has been proven to mitigate these complications and enhance recovery following surgery. Here we review the benefits of nerve-sparing surgery for deeply infiltrating disease