[Sentinel lymph node biopsy in the management of early-stage ovarian cancer: A systematic review of the literature]. / Place du ganglion sentinelle dans la prise en charge du cancer de l'ovaire de stade précoce : revue de la littérature.

The initial management of early-stage ovarian cancer consists of staging surgery including pelvic and para-aortic lymphadenectomy. The use of the sentinel lymph node (SLN) procedure in this setting may decrease the morbidity associated with this surgery. The objective of this review was to evaluate the feasibility of the SLN procedure in ovarian cancer diagnosed at an early stage by comparing the different techniques used and their accuracy. A systematic literature search was performed on PubMed and ClinicalTrials.gov for articles in English or French about the SLN technique in ovarian cancer. Ten studies were included in the analysis, with a total of 179 patients. The main tracers used were Technetium-99m, indocyanine green, and patent blue, and the most common site of injection was the proper ovarian and unfundibulopelvic ligaments. The overall detection rate was 87.7%. Of the small number of cases of lymph node metastasis reported, the SLN procedure had a sensitivity of 90.9% and a negative predictive value of 98.8%. The sentinel node procedure appears to be feasible and safe and could be reliable in determining the lymph node status of patients with early-stage ovarian cancer.

[Epithelial ovarian cancers and minimally invasive cytoreductive surgery after neoadjuvant chemotherapy: A systematic review]. / Cancers épithéliaux de l'ovaire et chirurgie de cytoréduction par voie mini-invasive après chimiothérapie néoadjuvante : revue systématique de la littérature.

INTRODUCTION: Advanced epithelial ovarian cancer (EOC) is associated with high mortality and often managed first with neoadjuvant chemotherapy (NACT) followed by debulking surgery. Laparoscopic surgery with or without robotic assistance (Minimally Invasive Surgery (MIS)) may represent a beneficial option for these patients. The objective of this literature review is to clarify the place of MIS in the management of advanced EOC for selected patients. METHOD: Pubmed, Cochrane and Clinicaltrials.gov online databases were used for this review, to select English or French published articles. RESULTS: We selected 11 original articles published between 2015 and 2020, 6 of which compared MIS and laparotomy. Among these 11 studies, 8 were retrospective cohorts, 2 were phase II trials, and one was a case-control study. In total, there were 3721 patients, of which 854 (23%) were treated with MIS. The robotic assistance was used with 224 patients (26%) of those MIS patients. Looking specifically at MIS patients, the laparoconversion rate was 9.5%, the rate of complete resection (CC-0) was 83.4%. Finally, the MIS complication rate was 1% intraoperatively and 12% postoperatively. The rate of complete resection, postoperative complication, as well as overall survival (OS) were comparable between patients treated with MIS or laparotomy. One study found an improved disease-free survival (DFS) in MIS versus laparotomy (18 months versus 12 months; P=0.027). CONCLUSION: MIS seems feasible, effective, and reliable in comparison to laparotomy for the completion of cytoreductive surgery after NACT without compromising oncological safety. Prospective randomized controlled trials are needed to confirm the role of MIS in advanced EOC.

Lomboaortic Lymphadenectomy in Gynecological Oncology: Laparotomy, Laparoscopy or Robot-Assisted Laparoscopy?

BACKGROUND: The outcomes of paraaortic lymphadenectomy were compared for the treatment of gynecological malignancies to identify the most appropriate surgical approach. METHODS: Our retrospective, multicentric study included 1304 patients who underwent paraaortic lymphadenectomy for gynecological malignancies. The patients were categorized into the following five groups based on treatment type: transperitoneal laparoscopy (group A, n = 198), extraperitoneal laparoscopy (group B, n = 681), robot-assisted transperitoneal laparoscopy (group C, n = 135), robot-assisted extraperitoneal laparoscopy (group D, n = 44), and laparotomy (group E, n = 246). RESULTS: The prevalence of cancer types differed according to the surgical approach: there were more ovarian cancers in group E and more cervical cancers in groups B and D (p < 0.001). Estimated blood loss was higher in group E (844.2 mL) than in groups treated with minimally invasive interventions (115.8-141.5 mL, p < 0.005). For infrarenal dissection, fewer nodes were removed in group C compared with the other approaches (16 vs. 21 nodes, respectively, p < 0.05). The average operative time ranged from 169 min for group A to 247 min for group E (p < 0.001). Length of hospital stay was 14 days for group E versus 3.5 days for minimally invasive procedures (p < 0.05). The early postoperative grade 3 and superior Dindo-Clavien complications occurred in 9-10% of the patients in groups B-D, 15% of the patients in group E, and only 3% and 4% for groups A and C, respectively. The most common complication was lymphocele. CONCLUSIONS: Laparotomy increases preoperative and postoperative morbidity. The robot-assisted transperitoneal approach demonstrated a poorer lymph node yield than laparotomy and extraperitoneal approaches.

Diffusion MRI: Technical principles and application to uterine cervical cancer.

Imaging is involved in the management of uterine cervical cancer with several objectives: 1/to assess local and lymph node extension of the initial disease; 2/evaluate treatment response to conservative therapy; 3/detect recurrences. Pelvic MRI is the first-line examination in all these indications. It is the key element for delineation after image fusion when the indication of chemoradiation therapy is made. It is also essential for guiding the placement of applicators and optimising the dosimetry of brachytherapy. The diffusion-weighted acquisition is a sequence sensitive to the motion of water molecules. It allows distinguishing water molecules with free diffusion from water molecules with diffusion restricted by obstacles such as cell membranes or the cytoskeleton. The diffusion is thus connected to the cellularity of the explored tissue, and the cancers, being hypercellular, will present a high signal. It thus provides additional information thanks to a high contrast between the tumour and the surrounding tissues, facilitating detection, evaluation of the volume and extent of the disease.

Risk factors for failure of bilateral sentinel lymph node mapping in early-stage cervical cancer.

BACKGROUND: The objective of this study was to determine clinical, tumoral and surgical factors associated with successful bilateral sentinel lymph node mapping (SBM) in early-stage cervical cancer. METHODS: We performed an ancillary work on the data of two prospective trials on SLN biopsy for FIGO IA-IIA cervical cancer (SENTICOL I & II). Patients having Sentinel lymph node (SLN) mapping for early-stage cervical cancer were included between 2005 and 2012 from 28 French oncologic centers. SLN was detected by a combined labeling technique (blue and isotopic). RESULTS: 405 patients were included for analysis: SLNs were identified on at least one side of the pelvis in 381 patients (94.1%) and bilaterally in 326 patients (80.5%). The mean age was 45.4 years [22-85 years]. Most patients had IB1 pathologic FIGO 2018 stage (81.3%) and squamous cell carcinoma (71%). Surgeries were mainly performed by minimally invasive approach (368 patients - 90.9%). By multivariate analysis, lower SBM rate was significantly associated with Age ≥70 years (ORa = 0.02, 95%CI = [0.001-0.28], p = 0.004), tumor size larger than 20 mm (ORa = 0.46,95%CI = [0.21-0.99], p = 0.048) and Body-mass index higher than 30 kg/m2 (ORa = 0.28, 95%CI = [0.12-0.65], p = 0.003). SBM rate was significantly higher in high skills centers (>5patients/year) (ORa = 8.05, 95%CI = [2.06-31.50], p = 0.003) and in SENTICOL II (2009-2012) compared to SENTICOL I (2005-2007) (ORa = 2.6, 95%CI = [1.23-5.51], p = 0.01). CONCLUSIONS: In early-stage cervical cancer, bilateral SLN detection rates is lower in patients aged more than 70years, patients with BMI≥30 kg/m2 and larger tumor ≥20 mm whereas stronger experience of SLN biopsy technique improves bilateral SLN detection.

[Prophylactic hysterectomy in Lynch syndrome: Feasibility and outcomes]. / Faisabilité et résultats de l'hystérectomie prophylactique dans le syndrome de Lynch.

OBJECTIVES: Lynch syndrome (LS) is a hereditary predisposition to cancers, first of all, colo-rectal and endometrial cancers in women. Although recommended, gynecologic screening has never proven its benefit. Prophylactic surgery can be considered once the parental project is completed. There are few data regarding the assessment of prophylactic surgery. The objectives of our study were to evaluate the feasibility and morbidity of prophylactic hysterectomy in patients with Lynch syndrome. METHODS: This is a descriptive retrospective study of consecutive patients with LS undergoing prophylactic hysterectomy at the Georges-Pompidou European Hospital from 2002 to 2016. We collected demographic characteristics, results of preoperative assessment, intra- and postoperative data, final pathologic result as well as postoperative follow-up data. RESULTS: Forty patients were included in the study, and seventeen women had a history of colon cancer surgery. All hysterectomies were performed by laparoscopy, with two cases of laparoconversion. Two intraoperative complications occurred: serosal small bowel injuries and superficial bladder injury. Two early postoperative complications occurred (a peritonitis on small bowel perforation and a peritonitis on left ureteral injury) and two late complications (vesico-vaginal fistula and adhesive small bowel obstruction). All operative specimens were benign. With a median follow-up of 28 months [5-52], no patient had peritoneal cancer. CONCLUSIONS: Our study shows that prophylactic hysterectomy in Lynch syndrome should be done with caution. Per and postoperative complication rates appear to be higher than in general population, probably related to a more frequent history of colorectal cancer. However, total hysterectomy with bilateral salpingo-oophorectomy appears to be an effective strategy for preventing gynecological cancers in women with the Lynch syndrome.

Predictive factors of unexpected lymphatic drainage pathways in early-stage cervical cancer.

OBJECTIVES: The purpose of this study was to describe sentinel lymph nodes (SLN) topography in patients with early-stage cervical cancer and to determine factors associated with atypical lymphatic drainage pathway (LDP). METHODS: We analyzed the data of two prospective multicentric trials on SLN biopsy for cervical cancer (SENTICOL I and II) in women undergoing surgery for early-stage cervical cancer. SLN detection was realized with a combined labeling technique (Patent blue and radioactive tracer). Patients having bilateral SLN detection were included. Univariate and Multivariate analysis were performed by patients and by side to assess clinical and pathologic factors that may predict atypical LDP. RESULTS: Between January 2005 and July 2012, 326 patients with 1104 intraoperative detected SLNs fulfilled the inclusion criteria. The SLNs were mainly located in the interiliac or external iliac area in 83.2%. The other localizations were: 9.2% in the common iliac area, 3.9% in the parametrium, 1.6% in the promontory area, 1.5% in the paraaortic area and 0.5% in other areas. Thirty-five patients (10.7%) had atypical SLN without SLN in typical area on one or both sides. In multivariate analysis, tumor size ≥20 mm appeared as an independent factor of having at least one exclusive atypical LDP (ORa = 3.95 95%CI = [1.60-9.78], p = 0.003). Multiparity decreased significantly the probability of having at least one exclusive atypical LDP (ORa = 0.16 95%CI = [0.07-0.39], p < 0.0001). CONCLUSIONS: Tumor size larger than 20 mm and nulliparity increase the risk of having exclusive atypical LDP in early-stage cervical cancer.

Predictive factors of severe perioperative morbidity of radical hysterectomy with lymphadenectomy in early-stage cervical cancer: A French prospective multicentric cohort of 248 patients.

OBJECTIVE: The purpose of this study was to assess the postoperative morbidity after radical hysterectomy (RH) for early-stage cervical cancer and to determine risk factors of severe perioperative morbidity. METHODS: Data of two prospective trials on sentinel node biopsy for cervical cancer (SENTICOL I & II) were analysed. Patients having a radical hysterectomy were included between 2005 and 2012 from 25 French oncologic centers. Postoperative complications were prospectively recorded in a pre-specified analysis. RESULTS: 248 patients met the inclusion criteria. The median age was 44.5 years [25-85]. 88.7% of patients had a stage IB1 disease. There were 71.4% epidermoid carcinomas and 25% adenocarcinomas. 125 patients (50.4%) had a laparoscopic-assisted vaginal RH, 88 patients (35.5%) had a total laparoscopic RH, 26 patients (10.5%) had an open RH and 9 patients (3.6%) had a robotic-assisted RH. Sixteen patients (6.4%) had intraoperative complications. On a multivariate analysis, intraoperative complications were significantly associated with BMI >30 kg/m2. The urinary, lymphovascular and neurologic complications rates were respectively 34.3%, 20.6% and 19.8%. 31 patients (12.5%) had severe postoperative complications (Clavien-Dindo ≥ 3 or CTCAE ≥ 3). On multivariate analysis, severe postoperative complications were associated with parametrial involvement, preoperative brachytherapy and inclusion in low surgical skills center. CONCLUSIONS: This study based on prospective data showed that RH has low severe postoperative complications. The main complications were urinary infections and lower limb lymphedema. Patients with early-stage cervical cancer should be referred to expert center to ensure best surgical outcomes.

[Acquisition of clinical observation skills by medical students improves with discipline-based teaching. The example of neurological examination]. / L'enseignement par discipline de la sémiologie en deuxième année de médecine améliore l'acquisition des compétences. Exemple de la sémiologie neurologique.

INTRODUCTION: Since 2014-2015, practical teaching of clinical observation skills for 2nd year medical students at our faculty has been discipline-based; previously, each clinical lecturer had to cover all medical fields. We assessed the impact of this teaching reform on the neurological examination skills of medical students in a before-and-after study. METHODS: Pre-reform 3rd and post-reform 2nd and 3rd year medical students (n=62, n=71 and 52, respectively) had to perform 7 neurological examination items, for which performance criteria had been pre-defined. Subsequently, we assessed whether the mean grade in neurological examination skills during the test at the end of the 2nd year was different between students who had received neurological teaching from a neurologist (n=29) or another specialist (n=102). RESULTS: The median [interquartile range] number of items acquired by post-reform 3rd year students (4 [2-5]) was higher than that of pre-reform 3rd year students (2 [1-3]; P<0.001), but lower than that of post-reform 2nd year students (5 [4-6]; P=0.01). The mean grade obtained during the practical test was not different in students trained by a neurologist or another specialist. CONCLUSION: Acquisition of neurological examination skills improved after the teaching reform which consisted of: (1) a discipline-based practical teaching of clinical observation skills; (2) a training of clinical lecturers to teach a limited list of educational objectives; and (3) the introduction of a practical test at the end of the 2nd year of medical studies. However, there was a decline in clinical observation skills between 2nd and 3rd year medical students.

[Multidisciplinary consultation for patients with HPV-related invasive carcinoma or precancerous lesions]. / Consultation multidisciplinaire pour les patients atteints d'une pathologie tumorale (carcinome infiltrant ou lésion précancéreuse) liée à HPV : la consultation multidisciplinaire papillomavirus.

Given the recent increase in the number of human papillomavirus (HPV)-induced cancers in other locations than gynaecological, the number of patients with two cancers at distinct sites, and because of the lack of exhaustive data, we decided to create a multidisciplinary network around an HPV consultation at the Georges-Pompidou European Hospital (HEGP). This network aims to set up the best tools for detecting HPV-associated "multisite" precancerous lesions in order to determine the possible impact of dedicated care for this at-risk population. This monthly consultation was created at the HEGP in June 2014. It is currently organized around five consultations: gynaecological, ENT, urological, digestive and immunological. Every patient who has been diagnosed with HPV-related cancer and whose care is provided at the HEGP is offered this particular follow-up: systematically, once the initial lesion has been treated, the patient is convened annually for a day during which it benefits from the consultations mentioned above. A consultation with a psychologist is systematically proposed. Local samples are taken at each site: a cytological examination, the analysis of known predictive and prognostic virological markers are carried out. This study fits more broadly in a theme of clinical and fundamental research around cancers related to HPV.

What about sentinel lymph node biopsy for early breast cancer during pregnancy?

Pregnancy-associated breast cancer is rare, but this clinical situation arises in 1/10,000-1/3000 pregnancies. In patients presenting an early-stage breast tumor devoid of clinically pathological lymph node, sentinel lymph node (SLN) biopsy has not yet been validated as a routine procedure for pregnant women due to the lack of data in the literature. The blue dye injection is not recommended because of 2% theoretical risk of anaphylactic shock. Several studies have shown that Tc99m injection at conventional dose between 12.1 and 18.5MBq exposed the fetus to an irradiation between 0.011 and 0.0245mSv much below the 50mSv recommended threshold. As evidenced by lymphoscintigraphy scans, the dose of injected Tc99m is localized at the injection site and in the SLN. According to the literature, the SLN technique does not seem to impact the fetal or obstetrical prognosis. Studies involving larger cohorts are required to confirm these data and to indicate this technique in pregnant women. Considering the benefit for the patient and the low risk incurred on both fetal and obstetrical levels, it appears reasonable to discuss the indication of SLN on a case-by-case basis in multidisciplinary oncologic meetings.

Morbidity of rectosigmoid resection in cytoreductive surgery for ovarian cancer. Risk factor analysis.

AIM: Rectosigmoid resection is often performed during cytoreductive surgery for ovarian cancer, to achieve the goal of no residual tumour. Here, we evaluated the morbidity associated with rectosigmoid resection and the underlying risk factors. METHODS: We retrospectively assessed consecutive patients managed with rectosigmoid resection during cytoreductive surgery for ovarian cancer at our centre in Paris, France, between 2005 and 2013. All previously identified risk factors were analysed. Major complications were defined as grade III-IV in the Clavien-Dindo classification. RESULTS: Of 228 patients, 116 had primary and 112 interval surgery; 43/228 [18.9%]; experienced major complications, and these were more common after primary surgery [24.1% vs. 13.4%, p = .04]. The 69 patients who had rectosigmoid resection [33 primary vs. 36 interval surgery, p = .32] had a higher morbidity rate compared to the other patients [30.4% vs. 14.6%, p = .006]. The anastomotic leakage rate was 2.89%. By multivariate logistic regression, independent risk factors for morbidity were postmenopausal status [adjusted odds ratio (aOR), 13.7; 95% confidence interval (95%CI), 1.2;161.9], surgery after neoadjuvant chemotherapy [aOR, 4.4; 95%CI, 1.1;18.8], and peritoneal stripping of the left; paracolic gutter [aOR, 11.3; 95%CI, 2.3;54.3]. CONCLUSION: The morbidity of rectosigmoid resection during cytoreductive surgery for ovarian cancer seems acceptable. Ileostomy does not seem associated with a lower risk of major complications or adjuvant bevacizumab with a higher complication rate.

[Benign metastasizing leiomyoma: An unusual cause of aggressive femoral bone tumor]. / Léiomyome métastatique bénin : une cause inhabituelle de tumeur osseuse fémorale agressive.

BACKGROUND: Benign metastasizing leiomyoma (BML) is a rare condition characterized by histologically benign "metastatic" smooth muscle tumors, which can affect women with history of uterine surgery. We report the case of a patient with bone metastases of BML. CASE REPORT: A 78-year-old woman who had undergone uterine surgery six years before hospital admission, was diagnosed with large pulmonary and pleural metastases that necessitated surgical removal. Pathological examination allowed the diagnosis of BML with positive staining for estrogen and progesterone receptors. Three years later, a BML metastasis in the right femoral diaphysis was unexpectedly discovered and treated by osteosynthesis because of a high risk of fracture. Despite an aromatase-inhibitor treatment, new lungs lesions appeared in the next few months. CONCLUSION: BML is a potential cause of aggressive, although histologically benign, bone tumor in women with a history of uterine surgery.

Networking for ovarian rare tumors: a significant breakthrough improving disease management.

BACKGROUND: Rare ovarian tumors represent >20% of all ovarian cancers. Given the rarity of these tumors, natural history, prognostic factors are not clearly identified. The extreme variability of patients (age, histological subtypes, stage) induces multiple and complex therapeutic strategies. METHODS: Since 2011, a national network with a dedicated system for referral, up to 22 regional and three national reference centers (RC) has been supported by the French National Cancer Institute (INCa). The network aims to prospectively monitor the management of rare ovarian tumors and provide an equal access to medical expertise and innovative treatments to all French patients through a dedicated website, www.ovaire-rare.org. RESULTS: Over a 5-year activity, 4612 patients have been included. Patients' inclusions increased from 553 in 2011 to 1202 in 2015. Expert pathology review and patients' files discussion in dedicated multidisciplinary tumor boards increased from 166 cases in 2011 (25%) to 538 (45%) in 2015. Pathology review consistently modified the medical strategy in 5-9% every year. The rate of patients' files discussed in RC similarly increased from 294 (53%) to 789 (66%). An increasing number (357 in 5 years) of gynecologic (non-ovarian) rare tumors were also registered by physicians seeking for pathological or medical advice from expert tumor boards. CONCLUSION: Such a nation-wide organization for rare gynecological tumors has invaluable benefits, not only for patients, but also for epidemiological, clinical and biological research.

Upper outer boundaries of the axillary dissection. Result of the SENTIBRAS protocol: Multicentric protocol using axillary reverse mapping in breast cancer patients requiring axillary dissection.

BACKGROUND: Two thirds of node-positive breast cancer patients have limited pN1 disease and could benefit from a less extensive axillary lymph node dissection (ALND). METHODS: 172 breast cancers patients requiring an ALND were prospectively enrolled in the Sentibras Protocol of Axillary Reverse Mapping (ARM). Radioisotope was injected in the ipsilateral hand the day before surgery. ALND was standard. Removed lymph nodes were classified into non radioactive nodes and radioactive nodes (ARM nodes). Among ARM nodes, nodes located in the upper outer part of the axilla, above the second intercostal brachial nerve and lateral to the lateral thoracic vein were identified as "zone D ARM nodes". The main objective was: feasibility of identification of the zone D ARM nodes. Secondary objectives were: metastatic involvement and lymphedema rate. RESULTS: 100% of patients had ARM nodes identified. The "zone D ARM nodes" were identified in 92% of cases. The rate of metastatic nodes was 60% in the all cohort, 31% in ARM nodes and 9% in zone D ARM nodes. Among those, metastatic rate was 6% in patients undergoing ALND for a positive sentinel node biopsy, 6% in case of primary ALND versus 14% after neo-adjuvant chemotherapy (p < 0.05). After 34 months of median follow up, 27% of interviewed patients had a lymphedema. CONCLUSION: The ARM technique reliably identifies the "zone D ARM nodes". These nodes can also easily be identified using knowledge of axillary anatomy. In selected patients, a selective ALND sparing the zone D ARM nodes could be performed.

[Anatomical consideration for the technique of nerve-sparing during radical hysterectomy for cervical cancer]. / Bases anatomiques et principe du nerve-sparing au cours de l'hystérectomie radicale pour cancer du col utérin.

Radical hysterectomy (RH) is an effective treatment for early-stage cervical cancer IA2 to IIA1 but RH is often associated with several significant complications such as urinary, anorectal and sexual dysfunction due to pelvic nerve injuries. Pelvic autonomic nerves including the superior hypogastric plexus (SHP), hypogastric nerves (HN), pelvic splanchnic nerves (PSN), sacral splanchnic nerves (SSN), inferior hypogastric plexus (IHP) and efferent branches of the IHP. We aimed to precise the neuroanatomy of the female pelvis in order to provide key-points of surgical anatomy to improve NSRH for cervical cancer. The SHP could be injured during periaortic lymph node dissection and its preservation necessitates an approach on the right side of the aorta and a blunt dissection of the promontory before lomboaortic lymphadenectomy. Injuries to HN can occur during the resection of USL at the posterior pelvic wall and of rectovaginal ligaments and to preserve HN only the medial fibrous part of the uterosacral ligament should be resected. The middle rectal artery, the deep uterine vein and the ureter should be identified to preserve PSN and IHP during resection of paracervix. Vesical branches can be preserved by blunt dissection of the posterior layer of the vesicouterine ligament after identifying the inferior vesical vein. In most of cases, NSRH for cervical cancer can be performed. Anatomical landmarks as middle rectal artery, deep uterine vein, inferior vesical vein and ureter and the respect of nervous part of uterine ligament and of parametrium provide to surgeon a safe preservation of pelvic innervation without compromising oncological outcomes.