Margin status after loop electrosurgical excision procedure (LEEP) and laser excision in patients with high-grade cervical neoplasia.

INTRODUCTION: Early management of high-grade cervical intraepithelial neoplasia is one of the key steps in cervical cancer prevention after vaccination and screening. It relies on lesion removal by surgical excision, and the French National Cancer Institute (INCa) in 2016 recommend using a loop electro excision procedure (LEEP). However, the laser excision method seems to be as effective with similar rates of negative excision margins and postoperative clearance of HPV. OBJECTIVE: The main objective of our study was to compare the laser excision method to LEEP by evaluating the quality of the surgical margins. We also studied factors associated with the status of the margins and the depth of cones. METHODS: We conducted a retrospective unicentric study between 2009 and 2017. RESULTS: Two hundred and thirty-one patients were included: 154 laser excisions and 77 LEEP. Negative surgical margin was achieved in 69.5 % of laser excisions and 72.7 % of LEEP (p = 0.649). Concerning factors predicting margin status, only a greater cone depth was associated with negative margins (OR: 0.91 (95 %CI: 0.84, 0.89); p = 0.02). The surgical technique was not found to be associated with the status of the margins (OR: 0.85 (95 %CI: 0.46,1.56); p = 0.61). Concerning factors predicting cone depth, only the LEEP was associated with a shorter cone depth (OR: 0.24 (95 %CI: 0.08, 0.69); p 0.008). Significant results are based on univariate analysis. CONCLUSION: No difference was found between the two technics concerning the rate of negative margins. However, LEEP seems to be associated with shorter cone depth in this study.

Clinical use of Indocyanine green fluorescence method for sentinel lymph node biopsy in breast cancer in France in 2021.

INTRODUCTION: Indocyanine green (ICG) for axillary sentinel lymph node (SLN) detection in early breast cancer is at least equivalent to radioisotopic and/or colorimetric techniques. This procedure has not yet been recommended by learned societies in France. Following the recent drug approval of Infracyanin ® in this indication, we wished to study the use of ICG in France. METHODS: We conducted a web-based survey among members of multiple French breast cancer societies throughout November 2021. The survey assessed the profile of the respondent, the use or not of ICG for the detection of SLN in breast cancer, the technique used and the opinion of non-users and their expectations on the subject. RESULTS: Seventy-five surgeons participated. More than a third (37 %) have been using ICG for the detection of SLN in breast cancer for 2 to 3 years. Technique was highly variable. According to 82.1 % of the respondents, less than 20 procedures are necessary to master the use of ICG. The main advantage reported for this method is the reduction of organizational constraints. The obstacles to the use of the ICG are the near infra-red camera equipment, but also the lack of validation by the French guidelines. Among non-users, 83 % would like to develop this technique in their center and 72.3 % are interested in training on this subject. CONCLUSION: This work highlights the need for French learned societies to take a stand on this issue but also the need to carry out studies on the technical aspects in order to standardise practices.

What is the most pertinent definition of malnutrition in epithelial ovarian cancer to assess morbidity and mortality?

INTRODUCTION: Malnutrition is common in ovarian cancer and is a major cause of morbidity and mortality. We aimed to define the most pertinent way to assess malnutrition in patients with epithelial ovarian cancer (EOC) in order to study its impact on morbidity (intra and post-operative complications) and survival (OS, overall survival and RFS, recurrence-free survival). METHODS: We retrospectively included all patients with EOC from 2003 to 2020. Nutritional status was assessed using the weight loss at diagnosis (more or <5%), albuminemia, the Nutritional Risk Index (NRI), and the Malnutrition Universal Screening Tool (MUST). RESULTS: Six hundred and fifteen patients were included. Among them, 34% declared having lost >5% of their usual weight, 58% had an albuminemia <35 g/L, 86% presented an abnormal NRI and 29% an abnormal MUST score. After univariate analysis, weight loss>5% appeared to be significantly associated with RFS. An abnormal NRI or MUST score were significantly associated with a decrease in OS in univariate analysis. None of the markers of malnutrition studied were correlated with morbidity. CONCLUSION: We were not able to reach a consensus concerning the most accurate definition to define malnutrition and predict morbidity and mortality in EOC. However, this modifiable prognosis factor must be systematically assessed and managed accordingly.

Patterns of recurrence in surgically treated women for TP53-mutated endometrial carcinomas.

OBJECTIVE: To describe the patterns of recurrence and the prognosis of patients with a recurrent TP53 mutated endometrial carcinoma treated initially by surgery. METHODS: All patients with endometrial carcinoma, treated at hospital European Georges Pompidou between 2001 and 2021 were retrospectively included. Patients were separated into two groups: TP53-mutated and not TP53-mutated (POLE/ultramutated-like (POLEmut), dMMR (mismatch repair-deficient) and NSMP (No specific molecular profile)). We estimated survival using recurrence free survival, overall survival and overall survival from recurrence. The risk of recurrence according to TP53 status and the type of recurrence (locoregional recurrence, peritoneal recurrence, and metastasis) were also compared between the two groups. RESULTS: Two hundred and ninety-one patients with endometrial carcinoma were included. Of these, 57 were TP53-mutated and 234 patients were not TP53-mutated. TP53 mutated patients had the worst recurrence free survival and overall survival (p < 0.001 for each). The hazard rate of recurrence was higher during the first three years for TP53 mutated endometrial carcinoma then tend to join the one of no TP53 mutated. There was a statistical difference between the two groups in terms of cumulative incidence of peritoneal recurrence (p = 0.002). There was, however, no statistical difference in overall survival from recurrence. CONCLUSIONS: TP53-mutated endometrial carcinoma were more likely to experience a recurrence during the first three years and most often peritoneal recurrence compared to not TP53-mutated. TP53 status in endometrial carcinoma could be useful to define follow-up. Further prospective studies are required to assess the predictive impact of TP53 mutation on chemotherapy benefit.

Prognostic impact of cytoreductive surgery conducted with primary intent, versus cytoreductive surgery after neoadjuvant chemotherapy, in the management of patients with advanced epithelial ovarian cancers: a multicentre, propensity score-matched study from the FRANCOGYN group.

OBJECTIVE: To compare survival and morbidity rates between primary cytoreductive surgery (pCRS) and interval cytoreductive surgery (iCRS) for epithelial ovarian cancer (EOC), using a propensity score. DESIGN: We conducted a propensity score-matched cohort study, using data from the FRANCOGYN cohort. SETTING: Retrospective, multicentre study of data from patients followed in 15 French department specialized in the treatment of ovarian cancer. SAMPLE: Patients included were those with International Federation of Gynaecology and Obstetrics (FIGO) stage III or IV EOC, with peritoneal carcinomatosis, having undergone CRS. METHODS: The propensity score was designed using pre-therapeutic variables associated with both treatment allocation and overall survival (OS). MAIN OUTCOME MEASURES: The primary outcome was OS. Secondary outcomes included recurrence-free survival (RFS), quality of CRS and other variables related to surgical morbidity. RESULTS: A total of 513 patients were included. Among these, 334 could be matched, forming 167 pairs. No difference in OS was found (hazard ratio, HR = 0.8, p = 0.32). There was also no difference in RFS (median = 26 months in both groups) nor in the rate of CRS leaving no macroscopic residual disease (pCRS 85%, iCRS 81.4%, p = 0.76). The rates of gastrointestinal tract resections, stoma, postoperative complications and hospital stay were significantly higher in the pCRS group. CONCLUSIONS: Analysis of groups of patients made comparable by propensity score matching showed no difference in survival, but lower postoperative morbidity in patients treated with iCRS.

Could uterine conservation be an option in presumed early-stage epithelial ovarian cancer?

PURPOSE: In early-stage epithelial ovarian cancer (EOC), patients usually undergo a hysterectomy. However, in fertility sparing surgery (FSS), carefully selected patients could conserve their uterus. The aim of our study was to evaluate the incidence and epidemiologic characteristics associated with uterine involvement in patients with early-stage EOC, outside of FSS. METHODS: We conducted a retrospective, monocentric, study from 2003 to 2019 and included all patients with a presumed early-stage EOC (FIGO I) who underwent a hysterectomy. The incidence of uterine involvement, predictive factors of uterine involvement, and the impact of uterine involvement on survival (recurrence-free survival and overall survival) were analyzed. RESULTS: Eighty-five patients had an early-stage EOC. Of these, six had an uterine involvement (7%). The populations of patients with or without uterine involvement did not differ except for CA 125 at diagnosis (136 ± 138 versus 356 ± 723, p = 0.04, respectively). No patient or tumor characteristics were predictive of uterine involvement. Uterine involvement was not associated with recurrence-free survival (HR = 1.26, IC95% 0.36-4.4, p = 0.72) or overall survival (HR = 0.7, IC95% 0.1-6.1, p = 0.77). CONCLUSION: Due to the small size of our sample, no conclusion can be drawn, yet it could be hypothesized that, for selected patients, a systematic hysterectomy could be discussed, notably in restaging surgery.

A Suggested Modification to FIGO Stage IV Epithelial Ovarian Cancer.

International Federation of Gynecology and Obstetrics (FIGO) staging classification for stage IV epithelial ovarian cancer (EOC) separates stages IVA (pleural effusion) and IVB (parenchymal and/or extra-abdominal lymph node metastases). We aimed to evaluate its prognostic impact and to compare survival according to the initial metastatic location. We conducted a multicenter study between 2000 and 2020, including patients with a FIGO stage IV EOC. Primary endpoint was overall survival (OS). The secondary endpoints were progression-free survival (PFS) and recurrence rates. We included 307 patients: 98 (32%) had FIGO stage IVA and 209 (68%) had FIGO stage IVB. The median OS and PFS of stage IVA patients were significantly lower than those of stage IVB patients (31 versus 45 months (p = 0.02) and 18 versus 25 months (p = 0.01), respectively). Recurrence rate was higher in stage IVA than IVB patients (65% versus 47% (p = 0.004)). Initial pleural involvement was a poor prognostic factor with a median OS of 35 months versus 49 months for patients without initial pleural involvement (p = 0.024). Patients with FIGO stage IVA had a worse prognosis than patients with FIGO stage IVB EOC. Pleural involvement appears to be relevant for predicting survival. We suggest a modification of the current FIGO staging classification.

Fluorescence guided surgery to improve peritoneal cytoreduction in epithelial ovarian cancer: A systematic review of available data.

During surgery for advanced epithelial ovarian cancer (EOC), the most important prognostic factor is the absence of residual tumor. Invisible microscopic peritoneal metastasis (mPM) are not removed during surgery and can be responsible of peritoneal recurrences. The aim of this current systematic review is to assess the role of fluorescence in evaluating mPM in EOC. We performed a systematic review using bibliographic citations from PubMed, Clinical Trials.gov, Embase, Cochrane Library, and Web of Science databases. MeSH terms for fluorescence, EOC and peritoneal carcinomatosis were combined and not restricted to the English language. The final search was performed on September 1rst, 2021. The primary outcome was to determine the diagnostic accuracy of fluorescence. We also reviewed the different techniques used. Eighty-seven studies were identified. Of these, 10 were included for analysis. The sensitivity and specificity of fluorescence ranged between 66.7-100% and 54.2-100%, respectively. Most importantly, the negative predictive value (NPV) ranged from 90 to 100% Due to the heterogeneity of the studies, no consensus was reached concerning the optimal use of fluorescence in terms of type of dye, type and timing of injection and imager to use. No adverse event was reported. Fluorescence can safely be used in EOC to evaluate mPM with a high NPV. However, a randomized controlled trial is needed to homogenize current practice.

Risks and benefits of systematic lymphadenectomy during interval debulking surgery for advanced high grade serous ovarian cancer.

BACKGROUND: Lymphadenectomy is debated in patients with ovarian cancer. The aim of our study was to evaluate the impact of lymphadenectomy in patients with high-grade serous ovarian cancer receiving neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS). METHODS: A retrospective, unicentric study including all patients undergoing NACT and IDS was carried out from 2005 to 2018. Patients with and without lymphadenectomy were compared in terms of recurrence free survival (RFS), overall survival (OS), and complication rates. RESULTS: We included 203 patients. Of these, 133 had a lymphadenectomy (65.5%) and 77 had involved nodes (57.9%). Patients without a lymphadenectomy were older, had a more extensive disease and less complete CRS. No differences were noted between the lymphadenectomy and no lymphadenectomy group concerning 2-year RFS (47.4% and 48.6%, p = 0.87, respectively) and 5-year OS (63.2% versus 58.6%, p = 0.41, respectively). Post-operative complications tended to be more frequent in the lymphadenectomy group (18.57% versus 31.58%, p = 0.09). In patients with a lymphadenectomy, survival was significantly altered if the nodes were involved (positive nodes: 2-year RFS 42.5% and 5-year OS 49.4%, negative nodes: 2-year RFS 60.7% and 5-year OS 82.2%, p = 0.03 and p < 0.001, respectively). CONCLUSION: Lymphadenectomy during IDS does not improve survival and increases post-operative complications.

[Place of PARP inhibitors in the treatment of endometrial and cervical cancers]. / Place des inhibiteurs de PARP dans le traitement des cancers de l'endomètre et du col de l'utérus.

New molecular therapeutic approaches have emerged in recent years for advanced gynaecological cancers, including targeted therapies such as poly-ADP-ribose polymerase inhibitors (PARPi). These have demonstrated efficacy in high-grade serous ovarian cancers in patients carrying a mutation in the BRCA gene, which predisposes them to breast and ovarian cancers. Clinical and pre-clinical data suggest that the activity of PARPi inhibitors may not be limited to BRCA mutated tumours and may involve the homologous recombination pathway. These data raise the question of the potential efficacy of PARPi in advanced endometrial and cervical cancers where treatment options are currently limited. At present, there are few data available on the activity of PARPi in endometrial and cervical cancers, but some results seem promising. In this review, we present a synthesis of the available studies concerning PARPi in endometrial and cervical cancer.

What can we learn from the 10 mm lymph node size cut-off on the CT in advanced ovarian cancer at the time of interval debulking surgery?

INTRODUCTION: The benefit of a systematic lymphadenectomy is still debated in patients undergoing neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) in ovarian cancer (OC). The objective of this study was to evaluate the predictive value of the pre-NACT and post-NACT CT in predicting definitive histological lymph node involvement. The prognostic value of a positive node on the CT was also assessed. MATERIEL AND METHODS: A retrospective, unicentric cohort study was performed including all patients with ovarian cancer who underwent NACT and IDS with a lymphadenectomy between 2005 and 2018. CT were analyzed blinded to pathology, and nodes with small axis ≥ 10 mm on CT were considered positive. Sensitivity (Se), specificity (Sp), and negative (NPV) and positive predictive values (PPV) and their CI95% were calculated. The 2-year recurrence free survival (RFS) and 5-year overall survival (OS) was compared. RESULTS: 158 patients were included, among which 92 (58%) had histologically positive lymph nodes. CT had a Se, Sp, NPV and PPV of 35%, 82%, 47% and 73% before NACT and 20%, 97%, 47% and 91% after NACT, respectively. Patients with nodes considered positive had a non-significant lower 2-year RFS and 5-year OS on the pre-NACT and post-NACT CT. Patients at 'high risk' (nodes stayed positive on the CT or became positive after NACT) also had a non-significant lower 2-year RFS and 5-year OS. CONCLUSION: Presence of enlarged lymph nodes on CT is a weak indicator of lymph node involvement in patients with advanced ovarian cancer undergoing NACT. However, it could be used to assess prognosis.

Complete pathological response to olaparib and bevacizumab in advanced cervical cancer following chemoradiation in a BRCA1 mutation carrier: a case report.

BACKGROUND: Homologous recombination deficiency is a marker of response to poly(ADP-ribose) polymerase inhibitors in different cancer types including ovary, prostate, and pancreatic cancer. To date, no report about poly(ADP-ribose) polymerase inhibitors has been published on cervical cancer. CASE PRESENTATION: Here we present the case of a patient with cervical cancer treated in this setting. A 49-year-old woman diagnosed with International Federation of Obstetricians and Gynecologists stage 2018 IIIC2 locally advanced undifferentiated cervical cancer received first-line chemoradiotherapy followed by carboplatin, paclitaxel, and bevacizumab with partial response. Because of a family history of cancers, the patient was tested and found positive for a pathogenic BRCA1 germline and somatic mutation, which motivated bevacizumab plus olaparib maintenance treatment. A simple hysterectomy was performed after 2 years stable disease; pathological report showed complete pathological response, and 12 months follow-up showed no recurrence. CONCLUSION: Poly(ADP-ribose) polymerase inhibitors could be an alternative maintenance treatment for patients with persistent advanced cervical cancer previously treated with platinum, especially when familial history of cancers is reported. Clinical trials using poly(ADP-ribose) polymerase inhibitors for advanced cervical cancer are warranted.

Docking for robotic extraperitoneal para-aortic lymphadenectomy with Da Vinci Xi surgical system.

Regarding extraperitoneal para-aortic lymphadenectomy, installation is key when performed with the assistance of the Da Vinci Xi robotic system. We developed a step-by-step guide, from patient installation to placement of the trocars to patient cart docking, to perform in the efficient and safest installation possible this procedure. The operation does not differ from standard laparoscopic extraperitoneal lymphadenectomy. The benefits of robotic surgery in this indication are comparable to those of the standard laparoscopic approach. Those benefits imply a precise knowledge of the management and installation of the da Vinci Xi robotic system.

Endocervical microglandular hyperplasia: Colposcopic aspects, physiopathology and differential diagnosis.

Endocervical microglandular hyperplasia (MGH) is a reactive type of glandular lesion that may be confused with endocervical adenocarcinoma from the macroscopic and the colposcopic findings, as well as from a histological. Differential diagnosis is very important. Here, we report a case of a 21 years-old women with a challenging differential diagnosis in the colposcopy and a MGH as histological finding.

Diagnostic value of indocyanine green fluorescence guided sentinel lymph node biopsy in vulvar cancer: A systematic review.

INTRODUCTION: Sentinel lymph node biopsy (SLN) helps define lymph node status, a major prognostic factor in vulvar cancer. The aim of the current systematic review was to assess the use of indocyanine green (ICG) coupled with near-infrared (NIR) fluorescence imaging in SLN mapping in vulvar cancer in terms of technique used, feasibility and accuracy. DATA SOURCES: We performed a systematic review using bibliographic citations from PubMed, Clinical Trials.gov, Embase, Cochrane Library, and Web of Science databases. MeSH terms for SLN, ICG and vulvar cancer were combined and restricted to the English language. The final search was performed on May 28, 2020. The primary outcome was to determine if the use of ICG alone in detecting SLN in women with vulvar cancer is as accurate as the gold standard dual labeling technique. RESULTS: Of the 34 studies initially identified, 13 were included for analysis. The SLN detection rate with ICG and NIR fluorescence ranged from 89.7 to 100%. No studies demonstrated the superiority of other detection techniques compared to ICG and NIR imaging. Lower SLN detection rates were found in studies with the most metastatic lymph nodes. No consensus was reached concerning the optimal use of ICG in terms of: injection timing or site; concentrations or volume of ICG; or use of human serum albumin or hybrid tracer. No adverse events were reported. CONCLUSION: ICG for SLN mapping appears to be safe in women with vulvar cancer with a detection rate similar to the current techniques. A large prospective randomized controlled study with optimization of the technique is necessary to homogenize current practice and determine the true value of ICG in vulvar cancer. PROSPERO ID: CRD42020178261.

Clinical Impact of Lymphadenectomy after Neoadjuvant Chemotherapy in Advanced Epithelial Ovarian Cancer: A Review of Available Data.

Recent robust data allow for omitting lymph node dissection for patients with advanced epithelial ovarian cancer (EOC) and without any suspicion of lymph node metastases, without compromising recurrence-free survival (RFS), nor overall survival (OS), in the setting of primary surgical treatment. Evidence supporting the same postulate for patients undergoing complete cytoreductive surgery after neoadjuvant chemotherapy (NACT) is lacking. Throughout a systematic literature review, the aim of our study was to evaluate the impact of lymph node dissection in patients undergoing surgery for advanced-stage EOC after NACT. A total of 1094 patients, included in six retrospective series, underwent either systematic, selective or no lymph node dissection. Only one study reveals a positive effect of lymphadenectomy on OS, and two on RFS. The four remaining series fail to demonstrate any beneficial effect on survival, neither for RFS nor OS. All of them highlight the higher peri- and post-operative complication rate associated with systematic lymph node dissection. Despite heterogeneity in the design of the studies included, there seems to be a trend showing no improvement on OS for systematic lymph node dissection in node negative patients. A well-conducted prospective trial is mandatory to evaluate this matter.

Does a pre-operative conization improve disease-free survival in early-stage cervical cancer?

PURPOSE: Ever since the recent findings showing the lack of benefit of minimally invasive surgery (MIS) versus open surgery in early-stage cervical cancer, gynecologists have tried to explain these results. The primary objective of our study was to assess the impact of pre-operative conization on disease-free survival (DFS) in early-stage cervical cancer. The secondary objective was to analyze the peri-operative morbidity associated with a pre-operative conization. METHODS: All patients undergoing a surgical management for early-stage squamous carcinoma or adenocarcinoma cervical cancer (IA1, IA2, IB1 and IB2 FIGO 2018) at a French university hospital from 2004 to 2018 were retrospectively included. We examined the association between conization and DFS using a Cox regression model. We also analyzed the morbidity associated with pre-operative conization. RESULTS: 48.4% (44/91) of the patients had a pre-operative conization (defined by a conization up to 90 days prior to surgery). 86.8% underwent MIS. There was a non-significant increase in the DFS with one patient presenting a recurrence in the conization group (2.3%) and six (12.8%) in the no conization group (log rank = 0.09). In univariate analysis, conization, definitive FIGO stage and pre-operative tumor size were associated with DFS (p < 0.2). Only pre-operative tumor size was significantly associated with DFS in multivariate analysis. There was a non-significant increase of adverse events in the conization group (43.2% in the conization group versus 23.4%, p = 0.06). CONCLUSION: Conization, through a reduction of tumor size, could improve DFS. Carefully selected patients could still benefit from minimally invasive surgery.

Use of fluorescence to guide surgical resection in vulvo-vaginal neoplasia: Two case reports.

We report hereby two cases of fluorescence-guided surgical resection with Indocyanine green in vulvo-vaginal neoplasia. The first case was a 86-year old patient who had a high-grade squamous intraepithelial lesion of the left small lip and on the vulvar fork. After a first incomplete surgery, a second fluorescence-guided vulvectomy was performed with ICG injected intravenously to determine intraoperatively surgical margins. At final pathologic examination, surgical margins were free of disease and postoperative course was uneventful. The second case was a 44-year old patient who had a clear cell carcinoma of the upper vagina. She underwent a fluorescence-guided colpo-hysterectomy with pelvic lymphadenectomy. ICG was injected one centimeter around the tumor and highlighted intraoperatively the limits of the vaginal resection. On the specimens, surgical margins were also negative. Peritumoral or intravenous injection of ICG are promising techniques for the intraoperative identification of surgical margins in gynecologic malignancies.