Long-term outcomes after percutaneous cryoablation of abdominal wall endometriosis.

OBJECTIVE: To retrospectively evaluate the long-term outcomes after percutaneous cryoablation of abdominal wall endometriosis (AWE). METHOD: The Institutional Review Board approved this retrospective observational review of 40 consecutive patients, of a median age of 37 years (interquartile range [IQR] 32-40 years), presenting with a total of 52 symptomatic AWE nodules. All patients underwent cryoablation between January 2013 and May 2022 with a minimum follow-up period of 12 months. Outcomes were assessed using a visual analog scale (VAS) that measured pain, as well as by magnetic resonance imaging (MRI). The pain-free survival rates were derived using the Kaplan-Meier estimator. Adverse events were analyzed and graded using the classification system of the Cardiovascular and Interventional Radiological Society of Europe. RESULTS: The median follow-up time was 40.5 months (IQR 26.5-47.2 months). The median VAS score before cryoablation was 8 (IQR 7-9). Complete relief of symptoms was documented in 80% (32/40) of patients at 3 months after initial cryoablation and correlated with the absence of residual endometriosis nodules on MRI. The median pain-free survival rates were 89.2% [95% CI, 70.1-96.4%] at 36 months and 76.8% [95% CI, 55.3-83.8%] after 60 months. No patient or lesion characteristics were found to be prognostic of failure. No major adverse events or side effects were reported in long term. CONCLUSION: Cryoablation safely and effectively afforded long-term pain relief for patients with AWE nodules. CLINICAL RELEVANCE STATEMENT: AWE cryoablation was found to be safe and effective in the long-term. KEY POINTS: • Cryoablation is highly effective with 80% of patients experiencing complete relief of AWE symptoms after a single procedure. • Cryoablation is safe without long-term adverse events or side effects. • The median pain-free survival rates are 89.2% at 36 months and 76.8% at 60 months.

Surgical and Percutaneous Image-guided Therapies of Abdominal Wall Endometriosis: a Systematic Review of Current Evidence.

OBJECTIVE: Despite various surgical and non-surgical strategies for abdominal wall endometriosis, the lack of definitive guidance on optimal treatment choice leads to clinical uncertainty. This review scrutinizes the safety and efficacy of abdominal wall endometriosis treatments to aid in decision-making. DATA SOURCES: We performed a systematic literature review of PubMed, Embase and Cochrane Library databases from 1947 until December 2023. METHODS OF STUDY SELECTION: A comprehensive literature search identified studies that assessed both surgical and nonsurgical interventions, including high-intensity focused ultrasound (HIFU), cryoablation, radiofrequency ablation (RFA), and microwave ablation (MWA). This review is registered in NIHR-PROSPERO (CRD 42023494969). Local tumor control (LTC), local pain relief (LPR) and adverse events (AE) were recorded. TABULATION, INTEGRATION, AND RESULTS: This review included 51 articles among 831 identified. All study designs were considered eligible for inclusion. A total of 2,674 patients are included: 2,219 patients (83%) undergoing surgery, and 455 (17%) undergoing percutaneous interventions (342 HIFU, 103 cryoablation, 1 RFA, 9 MWA). Follow-up length was 18 months in median, ranging from 1 to 235 months. Overall LTC rates ranged from 86% to 100%. Surgical interventions consistently demonstrated the highest rate of LTC with a median rate of 100%, and LPR with a median rate of 98.2% (95% confidence interval [CI]: 93.9-97.7). HIFU showed median LTC and LPR rates, respectively of 95.65% (95% CI, 87.7-99.9) and 76.1% (95% CI, 61.8-90.4); and cryoablation of 85.7% (95% CI, 66.0-99.9) and 79.2% (95% CI, 67.4-91.03). Minor AE were reported after surgery in 17.5% of patients (225/1284) including 15.9% (199/1284) of mesh implantation; 76.4% (239/313) after HIFU; and 8.7 % (9/103) after cryoablation. Severe AE were reported in 25 patients in the surgery group and 1 in the percutaneous group. CONCLUSION: The safety profile and efficacy of nonsurgical interventions support their clinical utility for management of abdominal wall endometriosis.

Fertility Outcomes after Surgical Management of Colorectal Endometriosis: A Single-center Retrospective Study.

STUDY OBJECTIVE: To assess the pregnancy rate after surgery for colorectal endometriosis. DESIGN: A retrospective, single-center study performed from January 2014 to December 2019. SETTING: A university tertiary referral center. PATIENTS: Patients with the intention to get pregnant younger than the age of 43 years, with or without a history of infertility and who were surgically managed for colorectal endometriosis. INTERVENTIONS: Complete excision of deeply infiltrating endometriosis. MEASUREMENTS AND MAIN RESULTS: The postoperative pregnancy rate was assessed. Seventy-seven patients had surgery; their mean age was 32.5 ± 4.4 years. Preoperative documented infertility was present in 77.9% of patients (n = 60). The mean length of history of infertility was 36.2 ± 24.9 months. The procedure was performed by laparoscopic surgery in 92.2% of patients (n = 71). Nonconservative, conservative, and mixed treatment were performed in 66.2% (n = 51), 29.9% (n = 23), and 3.9% of patients (n = 3), respectively. According to the Clavien-Dindo classification, the 3B complication rate was 6.5% (n = 5). The mean follow-up was 46.7 ± 20.6 months. Clinical pregnancies were defined by the presence of intrauterine pregnancy with an embryo with cardiac activity. The postoperative pregnancy rate was 62.3% (n = 48), and 54.2% (n = 26) were spontaneous. The mean number of pregnancies was 1.2 ± 0.4 per patient. In addition, 18.7% of patients (n = 9) got pregnant twice. The mean time from surgery to pregnancy was 13.8 ± 13.1 months. The live birth rate was 89.1% (n = 41). There were no significant differences concerning the prognostic criteria reported in the literature (antimüllerian hormone level, age, presence of adenomyosis). There were no predictive criteria for live births. CONCLUSION: According to this study, surgery for colorectal endometriosis results in a high postoperative pregnancy rate. Studies with a high level of evidence are needed to determine good candidates for this type of surgery.

Factors predicting the spontaneous regression of cervical high-grade squamous intraepithelial lesions (HSIL/CIN2).

PURPOSE: To determine clinical, pathological and virological factors predicting the spontaneous regression of HSIL/CIN2. METHODS: This retrospective study included 73 patients with HSIL/CIN2 diagnosed by biopsy between 2012 and 2016 and followed-up without treatment in the department of gynecology at Bordeaux University Hospital. All biopsies sampled inside or outside our department were reviewed and immunolabelled for p16 and Ki67. The response rate was the regression or the disappearance of HSIL/CIN2 as defined by the regression or the disappearance of initial colposcopic findings, cytological and/or histological results. RESULTS: The diagnosis of CIN2 was confirmed in 63 of 70 biopsies available for review. The Cohen's kappa coefficient was κ = 90%, indicating almost perfect inter-observer agreement. The lesion spontaneously regressed or disappeared in 36 of 60 patients (60%) with confirmed CIN2 during a median follow-up of 20 months (range 6-55). Baseline factors influencing the response rate were colposcopic findings (69% with minor change vs 31% with major change, p = 0.033), cytological results (72% with ASCUS/LSIL vs 28% with ASC-H/HSIL, p = 0.018), and HPV genotyping (71% with HPV not 16 vs 42% with HPV-16, p = 0.027). The other factors (age, smoking, surface area of the lesion, p16 and Ki67 expressions) did not significantly influence the outcome. CONCLUSION: Colposcopic findings, cytological results, and HPV genotyping were baseline factors predicting spontaneous regression of HSIL/CIN2.

Risk Factors of Post-Large Loop Excision of the Transformation Zone Recurrent High-Grade Cervical Intraepithelial Lesion: A Prospective Cohort Study.

OBJECTIVE: The aim of the study was to identify the risk factors of post-large loop excision of the transformation zone (LLETZ) recurrent disease and the impact of colposcopic guidance at the time of LLETZ on that risk. MATERIALS AND METHODS: From December 2013 to July 2014, 204 patients who had undergone LLETZ for the treatment of high-grade intraepithelial lesion with fully visible cervical squamocolumnar junction were included. The use of colposcopy during each procedure was systematically documented. The dimensions and volume of LLETZ specimens were measured at the time of the procedure before formaldehyde fixation. All participants were invited for a follow-up. The primary endpoint was the diagnosis of post-LLETZ recurrent disease defined as the histologic diagnosis of a high-grade cervical intraepithelial lesion. RESULTS: The median duration of post-LLETZ follow-up was 25.8 months. Recurrent disease was diagnosed in 8 (3.6%) patients. Older than 38 years (adjusted hazard ratio [aHR] = 11.9, 95% CI = 1.6-86.0), history of excisional therapy (aHR = 21.6, 95% CI = 3.5-135.3), and the absence of colposcopy for the guidance of LLETZ (aHR = 6.4, 95% CI = 1.1-37.7) were found to significantly increase the risk of post-LLETZ recurrent disease. The dimensions and volume of the specimen were not found to have any impact. Only positive endocervical margins were identified to significantly increase the risk of post-LLETZ recurrent disease (aHR = 14.4, 95% CI = 2.0-101.1). CONCLUSIONS: Risk factors of post-LLETZ recurrent disease are older than 38 years, history of excisional therapy, positive endocervical margins, and lack of colposcopic guidance at the time of LLETZ.

Risk Factors of Inadequate Colposcopy After Large Loop Excision of the Transformation Zone: A Prospective Cohort Study.

OBJECTIVE: The aim of the study was to identify the risk factors of post-large loop excision of the transformation zone (LLETZ) inadequate colposcopy. MATERIALS AND METHODS: From December 2013 to July 2014, a total of 157 patients who had a LLETZ performed for the treatment of high-grade intraepithelial lesion with fully visible cervical squamocolumnar junction were included. All procedures were performed using semicircular loops. The use of colposcopy made during each procedure was systematically documented. Dimensions and volume of LLETZ specimens were measured at the time of procedure, before formaldehyde fixation. All participants were invited for a follow-up colposcopy 3 to 6 months after LLETZ. Primary end point was the diagnosis of post-LLETZ inadequate colposcopy, defined by a not fully visible cervical squamocolumnar junction and/or cervical stenosis. RESULTS: Colposcopies were performed in a mean (SD) delay of 136 (88) days and were inadequate in 22 (14%) cases. Factors found to significantly increase the probability of post-LLETZ inadequate colposcopy were a history of previous excisional cervical therapy [adjusted odds ratio (aOR) = 4.29, 95% CI = 1.12-16.37, p = .033] and the thickness of the specimen (aOR = 3.12, 95% CI = 1.02-9.60, p = .047). The use of colposcopy for the guidance of LLETZ was statistically associated with a decrease in the risk of post-LLETZ inadequate colposcopy (aOR = 0.19, 95% CI = 0.04-0.80, p = .024) as the achievement of negative endocervical margins (aOR = 0.26, 95% CI = 0.08-0.86, p = .027). CONCLUSIONS: Although the risk of post-LLETZ inadequate colposcopy is increased in patients with history of excisional therapy and with the thickness of the excised specimen, it could be reduced with the use of colposcopic guidance and the achievement of negative endocervical margins.

Mid-term outcomes after percutaneous cryoablation of symptomatic abdominal wall endometriosis: comparison with surgery alone in a single institution.

OBJECTIVES: To compare the outcomes of percutaneous image-guided cryoablation of symptomatic abdominal wall endometriosis (AWE) versus surgery alone. METHODS: From 2004 to 2016, cryoablation or surgery alone was performed under local (n = 5) or general anaesthesia (n = 15) for AWE in a single institution in 7 (mean age, 36.1 years) and 13 (mean age, 31.9 years) patients, respectively. Fifteen lesions were treated by cryoablation (mean size, 2.3 cm; range, 0.5-7 cm) and 16 by surgery (2.5 cm; 1.1-3.4 cm). Tolerance, efficacy and patient and procedural characteristics were compared. RESULTS: Median follow-up was 22.5 (range, 6-42) months after cryoablation and 54 (14-149) after surgery. The median procedure and hospitalisation durations were 41.5 min (24-66) and 0.8 days (0-1) after cryoablation, and 73.5 min (35-160) and 2.8 days (1-12 days) after surgery (both P = 0.01). Three patients (23.1%) had severe complications and nine aesthetic sequels (69.2%) after surgery, none after cryoablation (P = 0.05). The median 12- and 24-month symptom free-survival rates were 100% and 66.7% (95% CI, 5.4; 94.5) after cryoablation and 92% (55.3; 98.9) after surgery at both time points (P = 0.45). CONCLUSIONS: Cryoablation presents similar effectiveness to surgery alone for local control of AWE while reducing hospitalisation duration and complications. Any aesthetic sequels were associated with the cryoablation treatment. KEY POINTS: • Hospitalisation is shorter after cryoablation than after surgery of abdominal wall endometriosis. • A significantly lower rate of complications is observed after cryoablation compared to surgery. • Cryoablation of abdominal wall endometriosis presents similar effectiveness to surgery alone. • A significant reduction of pain is observed 6 months after treatment. • A significant reduction of abdominal wall endometriosis is observed at 6 months.

Evaluation and Selection of Quality Indicators for the Management of Endometrial Cancer.

OBJECTIVE: The aim of this study was to evaluate 36 quality indicators (QIs) for monitoring the quality of care of uterine cancer to be implemented in the EFFECT (effectiveness of endometrial cancer treatment) project. METHODS: The 36 QIs were evaluated in the first 10 patients diagnosed with endometrial cancer and managed in 14 French hospitals in 2011. To assess the status of each QI, a questionnaire detailing the 36 QIs was sent to each hospital, and the information was cross-checked with information from the multidisciplinary staff meeting, surgical reports, and pathological reports. The QIs were evaluated in terms of measurability and improvability. The remaining QIs were evaluated with a multiple correspondence analysis to highlight the interrelationships between qualitative variables describing a population. RESULTS: Thirteen of the 14 institutions responded to the survey for a total of 130 patients. Twenty-five of the 36 QIs affected less than 80% of the patients. Thirteen QIs were found not to be improvable because they reached more than 95% of the theoretical target. Finally, 5 QIs concerning more than 80% of the patients were found to be improvable. The multiple correspondence analysis finally identified 3 dimensions-outcome, safety, and perioperative management-that included the 5 QIs. CONCLUSIONS: In the present study, 5 of the 36 QIs suggested by the EFFECT project seem to be sufficient to report on the quality of endometrial cancer management. Further studies are needed to correlate the information provided by those 5 questions and the relevant outcomes reflecting quality of care in endometrial cancer.

The Accuracy of Large Loop Excision of the Transformation Zone Specimen Dimensions in Determining Volume: A Multicentric Prospective Observational Study.

OBJECTIVE: The aim of the study was to determine which mathematical formula of specimen dimensions is the most accurate method of determining volume of the excised specimen at loop excision of the transformation zone. MATERIALS AND METHODS: A multicenter prospective observational study was conducted. A total of 258 patients who had a loop excision of the transformation zone performed as treatment of cervical intraepithelial neoplasia 2-3 were included. The dimensions and the volume of the specimen were measured at the time of the procedure, before formaldehyde fixation. The volume was measured by immersing the specimen in a graduated cylinder using Archimedes fluid displacement technique. The measured volume was compared with the calculated volume using different volume formulas, that is, a cone, a cylinder, a parallelepiped, and a hemiellipsoid. The main outcome measure was the relationship between calculated volume (using the dimensions of thickness, length, and circumference) and the measured volume of the specimen. RESULTS: The mean (SD) thickness, length, and circumference of specimens were 8.8 mm (3.8), 12.7 mm (5.9), and 45.7 mm (16.8), respectively. The mean (SD) measured volume was 2.53 (1.49) mL. Using the formula for the volume of a cone, a cylinder, a parallelepiped and a hemiellipsoid, estimated volumes were 1.03 mL (1.22), 3.10 mL (3.65), 6.20 mL (7.31), and 2.07 mL (2.44), respectively. The highest intraclass correlation coefficient between measured and calculated volume was observed when using the formula for the volume of a hemiellipsoid specimen (0.47, 95% CI = 0.36-0.56). CONCLUSIONS: The hemiellipsoid formula is the most accurate determinant of the excised volume. Other formulas do not allow for an accurate estimation of the excised volume.

Modified Gluteal Fold V-Y Advancement Flap for Reconstruction After Radical Vulvectomy.

OBJECTIVE: To describe the surgical technique of the V-Y cutaneous supra-fascial (modified) gluteal advancement flaps for reconstruction after radical vulvectomy and to assess the outcome of patients according to their clinical characteristics. METHODS: Between January 2006 and July 2012, 36 V-Y flaps were performed in 21 patients to cover the defect after radical surgery of primary vulvar cancers. Surgery duration, blood loss, hospital stay, and wound healing were assessed according to patient age, body mass index (BMI), American Society of Anesthesiologists (ASA) score, and the initial defect size. RESULTS: Median patient age, BMI, and ASA score were 80 (range, 31-91), 28 (range, 18-36), 3 (range, 1-3), respectively. Median surgery duration and blood loss were 180 minutes (range, 60-275) and 400 mL (range, 100-1000), respectively. Median operating time was higher in patients ASA3 than ASA less than 3, 200 versus 120 minutes (P = 0.038). Median initial defect size was higher in patients with BMI greater than 28 than 28 or less, 92 versus 55 cm (P = 0.004). Local scar defect was observed in 16 patients (76%), mild, less than 10 cm in 10 patients. Median wound healing duration was higher in patients with bilateral than unilateral flap, 16 versus 9.5 days (P = 0.034). CONCLUSIONS: The V-Y cutaneous suprafascial gluteal advancement flap for vulvar reconstruction after vulvectomy is an easy, safe, and reliable procedure. However, even mild local scar defect after bilateral flap may impact on wound healing and hospital stay, in elderly and ASA3 patients.

Benefits of Direct Colposcopic Vision for Optimal LLETZ Procedure: A Prospective Multicenter Study.

OBJECTIVE: The aim of the study was to assess whether direct colposcopic vision (DCV) of the cervix during large loop excision of the transformation zone (LLETZ) is associated with a decrease in the volume and dimensions of specimens or affects margin status at histology. MATERIALS AND METHODS: A prospective multicenter observational study of 216 women who underwent LLETZ for grades 2 and 3 cervical intraepithelial neoplasia was conducted. The volume and dimensions (circumference, length, and thickness) of the surgical specimens were measured before fixation. Data were compared according to the use of colposcopy during LLETZ. The following 3 groups were considered: LLETZ performed without colposcopy (n = 91), LLETZ performed immediately after colposcopy (n = 51), and LLETZ performed under DCV (n = 74). RESULTS: Patient characteristics were comparable with regard to age, parity, history of excision, indication of the procedure, and the size of the cervix. We found a significant decrease in all dimensions of the specimens obtained under DCV (p < .001). Margin status was not affected. After adjusting for confounders, the mean volumes were significantly lower in the DCV group (adjusted mean difference = -0.66 mL; 95% CI = -1.17 to -0.14). The probability that negative margins would be achieved together with the attainment of a volume less than 5 mL and a thickness less than 10 mm was the highest in the DCV group (adjusted OR = 2.80; 95% CI = 1.13 to 6.90). CONCLUSIONS: Direct colposcopic vision is associated with a significant decrease in the volume and in all dimensions of LLETZ specimens with no compromise in the margin status.

Management of Stage I Endometrial Cancer in France: A Survey on Current Practice.

PURPOSE: We conducted a survey to assess the performance of preoperative staging and the application of French surgical guidelines in women with presumed stage I endometrial cancer (EC). METHODS: The survey included 26 questions about the number of patients in low-, intermediate-, and high-risk groups operated on in 2012, the proportion of patients upstaged or downstaged by the examination of the uterus, and the proportion of subsequent surgery for lymph node dissection. RESULTS: Thirty-two (70 %) of the 46 French university hospitals responded to the questionnaire. Among 886 patients with EC treated, 661 had stage 1 EC. The rates of presumed preoperative type 1 low-, intermediate-, high-risk EC and type 2 EC were 310 (46.9 %), 218 (33 %), 39 (5.9 %), and 94 (14.2 %) respectively. Among 567 type 1 patients, 35 % were upstaged and 6 % were downstaged. Fair agreement was found between preoperative and postoperative risk assessment (κ = 0.37). Patients with presumed low- and intermediate-risk EC upstaged postoperatively to FIGO stage II/III were more likely to have a restaging operation than patients upstaged to type 1 high-risk FIGO stage I EC: 37/70 (52.8 %) versus 26/75 (34.6 %), p = 0.027. The proportions of patients undergoing the recommended subsequent pelvic and/or para-aortic lymph node dissection were low: 34/85 (40 %) and 47/145 (32.4 %) respectively. Lymph node samplings were mainly performed by laparoscopy: 31/34 (91.2 %) and 40/47 (85.1 %) for pelvic and para-aortic dissection respectively. CONCLUSIONS: Our survey showed that the performance of preoperative assessment of FIGO stage I EC was moderate and that adherence to the guidelines was low.

[Prevention and screening of cervical cancer]. / Prévention et dépistage des cancers du col de l'utérus.

Cervical cancer may be prevented by human papillomavirus (HPV) vaccination and the treatment of intraepithelial lesions diagnosed using cervical pap smears. HPV vaccines are effective for the prevention of CIN2/3 related to HPV 16, 18 and some other oncogenic HPV subtypes in HPV-naïve women. They are very well tolerated and to date, no increase in the incidence of auto-immune diseases has been reported. HPV vaccines primarily target girls aged 11-14 years old and catch-up programs include girls aged 15-19 years old. Vaccination coverage is below 40% in France, which is insufficient to induce herd immunity. Screening via pap smears is performed every three years in women between 25 and 65 years old, after two normal annual smears. However, screening is an individualised decision and is only performed in 57% of women. Abnormal smears require subsequent diagnostic investigations. Apart from high grade intra-epithelial lesions which generally require treatment, these abnormalities may be observed as they often undergo spontaneous regression due to viral clearance.

Percutaneous cryoablation of symptomatic uterine adenomyomas: Initial experience.

OBJECTIVE: To assess the efficacy and safety of percutaneous image-guided cryoablation of adenomyomas MATERIAL AND METHODS: Five symptomatic women who wanted to preserve their uterus and fertility underwent a single session of percutaneous image-guided cryoablation of adenomyoma. Three to six 17-gauge cryoprobes were introduced percutaneously into the adenomyoma under ultrasound and laparoscopy guidance. Clinical efficacy was defined as the diminution of the Visual Analogue Scale of pain (VAS), the decrease in uterine bleeding and the improvement of quality of life assessed by the endometriosis health profile 5 (EHP-5) 12 months after treatment. Technical efficacy was defined by the reduction in volume of each treated adenomyoma on MRI. Complications were classified using the Clavien-Dindo classification system. Hysterosonography was performed at least 3 months after the procedure. RESULTS: Compared to the baseline, all symptom scores had decreased after 12 months: median VAS 8/10 (range, 5-10) to 4/10 (range, 0-7); median dyspareunia score 7/10 (range, 0-10) to 2/10 (range, 0-8); median bleeding score 335 (range, 102-920) to 76 (range, 0-88); median EHP-5 score 60/100 (range, 50-75) to 50/100 (range, 32-55). The median volume of adenomyosis decreased from 57 cm3 (range, 8-87) to 9 cm3 (range, 2-45) at 12 months. No postoperative complications occurred. Two patients had incomplete intrauterine adhesions that were easily removed hysteroscopically. CONCLUSION: Cryoablation may be a promising alternative treatment for symptomatic adenomyoma in women who want to preserve their uterus.

Regression of cervical high-grade squamous intraepithelial lesions (HSIL/CIN2) managed expectantly.

OBJECTIVES: Many women with cervical high-grade squamous intraepithelial lesions (HSIL/CIN2) are managed expectantly, because about half of them will regress spontaneously, thus avoiding systematic loop electrosurgical excision procedure and related adverse effects. However, most of the guidelines have restricted this strategy to the youngest women. The objectives of our study were to determine the rate and the predictors of regression of HSIL/CIN2 managed expectantly. STUDY DESIGN: This retrospective study included 128 patients under 40 years of age (median 29, range 21-39), and HSIL/CIN2 diagnosed by biopsy between 2012 and 2019. They were followed-up without treatment in the department of gynecology at Bordeaux University Hospital, France. The regression of HSIL/CIN2 was defined by the regression or the disappearance of initial colposcopic findings, cytological and/or histological results. RESULTS: The lesion spontaneously regressed or disappeared in 76 (59%) patients during a median follow-up of 25 months (range, 7-86). In the multivariable analysis, minor change at colposcopy (odds ratio OR = 2.8 (CI95% 1.2-6.9), P = 0.02), low grade lesions (ASC-US/LSIL) by cytology (OR = 4.1 (CI95% 1.7-10.1), P < 0.001), and infection by HPV other than HPV-16 (OR = 5.4 (CI95% 2.3-13.9), P < 0.001) predicted the spontaneous regression of HSIL/CIN2. CONCLUSIONS: Colposcopic findings, cytological results, and HPV genotyping, but not the age, were baseline factors predicting the evolution of HSIL/CIN2 in patients under 40.

Regression of high-grade cervical intraepithelial neoplasia with TG4001 targeted immunotherapy.

OBJECTIVE: We sought to evaluate the safety and efficacy of TG4001 in patients with human papillomavirus (HPV) 16-related cervical intraepithelial neoplasia (CIN) 2/3 at 6 and 12 months. STUDY DESIGN: In all, 21 patients with HPV 16-related CIN 2/3 received 3 weekly subcutaneous injections of TG4001. Regression of the CIN 2/3 lesion and the clearance of HPV 16 infection were monitored by cytology, colposcopy, and HPV DNA/messenger RNA (mRNA) detection. A clinical response was defined by no CIN 2/3 found on conization, or no conization performed because not suspected at cytology or colposcopy. RESULTS: Ten patients (48%) were evaluated as clinical responders at month 6. Nine patients experienced an improvement of their HPV 16 infection, by mRNA ± DNA eradication. HPV 16 mRNA clearance was associated with CIN 2/3 cytologic and colposcopic regression in 7 of 10 patients. At month 12, 7 of 8 patients without conization reported neither suspicion of CIN 2/3 relapse nor HPV 16 infection. The remaining patient was lost to follow-up. CONCLUSION: These promising data warrant further development of TG4001 in CIN 2/3 treatment.

Ulipristal acetate use in adenomyosis: A randomized controlled trial.

OBJECTIVE: To evaluate the effect of a 10 mg per day 12 week treatment of ulipristal acetate (UPA) on abnormal uterine bleeding due to adenomyosis. DESIGN: A double-blind phase 2 randomized controlled pilot study. SETTING: From May 2015 to February 2018 in five teaching hospitals. POPULATION: Premenopausal women with abnormal uterine bleeding (with a pictorial blood loss assessment score (PBAC) higher than 100 at inclusion) and a sonographic or MRI diagnosis of adenomyosis. METHODS: After random allocation, either UPA 10 mg or placebo were orally administered during 12 weeks. A 3:1 ratio was used. MAIN OUTCOME MEASURES: The primary outcome was the rate of women with a PBAC score of less than 75 as evaluated over the 28 days following the 12-week treatment. Secondary outcomes included rate of amenorrhea, evolution of pain, quality of life and tolerance. RESULTS: Thirty women were included in the UPA group and 10 in the placebo group. No woman in the placebo group versus 95.24 % of women in the UPA group had a PBAC score under 75 during the 28 day period following the 12-week treatment (p < 0.01). A significant decrease in pain was noticed between inclusion and 13 weeks in the UPA group (p < 0.01). At 6 months, there was no significant difference in PBAC score or pain between groups. No serious adverse event was recorded. CONCLUSION: UPA could be an interesting option for treatment of abnormal uterine bleeding related to adenomyosis in women wishing to preserve their fertility.

Borderline ovarian tumors: French guidelines from the CNGOF. Part 2. Surgical management, follow-up, hormone replacement therapy, fertility management and preservation.

In the Early Stages (ES) of Borderline Ovarian Tumor (BOT), if surgery without risk of tumor rupture is possible, then laparoscopy with protected extraction is recommended over laparotomy (Grade C). In case of bilateral serous ES BOT treatment with a strategy to preserve fertility and/or endocrine function, bilateral cystectomy is recommended if possible (Grade B). In case of mucinous BOT treatment with a strategy to preserve fertility and/or endocrine function, unilateral adnexectomy is recommended (grade C). In the case of a mucinous BOT in a patient who has had an initial cystectomy, unilateral adnexectomy is recommended (grade C). In the case of treatment of a serous ES BOT in a patient who has had an initial cystectomy, with a strategy to preserve fertility and/or endocrine function, restaging surgery for adnexectomy is not recommended in the absence of suspicious residual lesions at the time of surgery and/or postoperative imaging (reference ultrasonography or pelvic MRI) (grade C). For serous or mucinous ES BOTs, routine hysterectomy is not recommended (Grade C). In cases of ES BOTs, lymphadenectomy is not recommended (Grade C). For ES BOTs, appendectomy is recommended only if there is a macroscopically pathological aspect to the appendix (Grade C). Restaging surgery is recommended in case of a serous BOT with a micropapillary aspect and an unsatisfactory inspection of the abdominal cavity during initial surgery (Grade C). Restaging surgery is recommended in cases of mucinous BOT if only a cystectomy has been performed or if the appendix has not been evaluated (Grade C). If restaging surgery is decided for an ES BOT, the following procedures should be performed: peritoneal cytology (grade C), omentectomy (there is no data in literature to recommend which type of omentectomy should be performed) (grade B), complete exploration of the abdominal cavity with peritoneal biopsies (grade C), visualization of the appendix +/- appendectomy in case of pathological macroscopic appearance (grade C) and unilateral adnexectomy in case of a mucinous BOT (grade C). In advanced stages of BOT it is not recommended to perform a lymphadenectomy as a routine procedure (Grade C). In cases of an advanced stage BOT, in a patient with a desire to fall pregnant, conservative treatment involving preservation of the uterus and all or part of the ovary may be proposed after a multidisciplinary meeting (Grade C). Second surgery aimed at removing all lesions, if not performed initially, is recommended in cases of advanced stage BOT (Grade C). It is not recommended to perform completion surgery after conservative treatment (preservation of the ovaries and the uterus) and after the achievement of fertility desire for a serous BOT (Grade B). After treatment for a BOT, follow-up beyond 5 years is recommended due to the median time to recurrence (Grade B). It is recommended that a systematic clinical examination be carried out during follow-up of a treated BOT (Grade B). In the particular case of an initial elevation of CA 125 levels, it is recommended to monitor CA 125 during follow up (Grade B). In cases treated conservatively (ovarian and uterine conservation), it is recommended to use endovaginal and transabdominal ultrasonography during the follow up period (Grade B). In the event of a recurrence of a BOT, in a woman of childbearing age, a conservative treatment strategy can again be proposed (Grade C). In the presence of non-invasive BOT implants, conservative treatment may be considered after a first non-invasive recurrence in women who wish to preserve their fertility (Grade C). Pelvic MRI is recommended after 12 weeks of amenorrhea in case of an undetermined adnexal mass and should be concluded with a diagnostic score (Grade C). The injection of gadolinium, in case of pregnancy, should be discussed on a case-by-case basis due to the proven risks for the foetus (Grade C). If feasible, a laparoscopic approach should be preferred during pregnancy (Grade C). A consultation with a specialist reproductive physician should be offered to patients with a BOT and of childbearing age (Grade C). It is recommended that patients be provided with full information on the risk of decreased ovarian reserve following to surgical treatment. It is recommended that the ovarian reserve be evaluated prior to surgical management of a suspected BOT (Grade C). When possible, a conservative surgical strategy is recommended to preserve fertility in women of childbearing age (Grade C). There is no specific data on the management of infertility following to conservative treatment of BOT. In case of durable infertility following to conservative treatment of BOT, a consultation with a specialist reproductive physician is required (Grade C). In the case of optimally treated BOT, there is no evidence in literature to contraindicate the use of Assisted Reproductive Techniques (ART). The use of hormonal contraception after serous or mucinous BOT is not contraindicated (Grade C). After treatment of a mucinous BOT, for women aged under 45 years, given the benefit of hormonal replacement therapy (HRT) on cardiovascular and bone risks, and the lack of hormone-sensitivity of mucinous BOTs, it is recommended to offer HRT (Grade C). After treatment of a mucinous BOT, for women over 45 years of age, there is no argument to contraindicate the use of HRT. HRT can be prescribed in case of a climacteric syndrome, as part of an individual benefit to risk assessment (Grade C).

Borderline ovarian tumors: French guidelines from the CNGOF. Part 1. Epidemiology, biopathology, imaging and biomarkers.

The incidence (rate per 100 000) of borderline ovarian tumors (BOTs) increases progressively with age, starting at 15-19 years and peaking at around 4.5 cases per 100 000 at an age of 55-59 years (LE3) with a median age of 46 years. The five year survival for FIGO stages I, II, III and IV is 99.7 % (95 % CI: 96.2-100 %), 99.6 % (95 % CI: 92.6-100 %), 95.3 % (95 % CI: 91.8-97.4 %) and 77.1 % (95 % CI: 58.0-88.3 %), respectively (LE3). An epidemiological association exists between the individual risk of BOT and family history of BOT and certain other cancers (pancreatic, lung, bone, leukemia) (LE3), a personal history of benign ovarian cyst (LE2), a personal history of tubo-ovarian infection (LE3), the use of a levonorgestrel intrauterine device (LE3), oral contraceptive use (LE3), multiparity (LE3), Hormonal replacement therapy (LE3), high consumption of Coumestrol (LE4), medical treatment for infertility with progesterone (LE3) and non-steroidal anti-inflammatory drug use (LE3). Screening for BOTs is not recommended for patients (Grade C). The overall risk of recurrence of BOTs varies between 2% and 24 %, with an overall survival greater than 94 % at 10 years, and the risk of an invasive recurrence of a BOT ranges from 0.5 % to 3.8 %. The use of scores and nomograms can be useful in assessing the risk of recurrence, and providing patients with information (Grade C). The WHO classification is recommended for classifying BOTs. It is recommended that the presence of a microinvasive focus (<5 mm) and microinvasive carcinoma (<5 mm with an atypical nuclei and a desmoplastic stroma reaction) within a BOT be reported. In cases of serous BOT, it is recommended to specify the classic histological subtype or micropapillary / cribriform type (Grade C). When confronted with a BOT, it is recommended that the invasive or non-invasive nature of peritoneal implants can be investigated based solely on the invasion and destruction of underlying adipose or peritoneal tissue which has a desmoplastic stromal reaction where in contact with the invasive clusters (Grade B). For bilateral mucinous BOTs and / or in cases with peritoneal implants or peritoneal pseudomyxoma, it is recommended to also look for a primitive digestive or pancreato-biliary cancer (Grade C). It is recommended to sample ovarian tumors suspected of being BOTs by focusing samples on vegetations and solid components, with at least 1 sample per cm in tumors with a size less than 10 cm and 2 samples per cm in tumors with a size greater than 10 cm (Grade C). In cases of BOTs and in the absence of macroscopic omental involvement after careful macroscopic examination, it is recommended to perform at least 4-6 systematic sampling blocks and to include all peritoneal implants (Grade C). It is recommended to consult an expert pathologist in gynecology when a BOT suspicion requires intraoperative extemporaneous histology (grade C). Endo-vaginal and suprapubic ultrasonography are recommended for the analysis of an ovarian mass (Grade A). In case of an undetermined ovarian lesion on ultrasonography, it is recommended that a pelvic MRI be performed (Grade A). To analyze an adnexal mass with MRI, it is recommended to use an MRI protocol with T2, T1, T1 Fat Sat, dynamic and diffusion sequences as well as gadolinium injection (Grade B). To characterize an adnexal mass with MRI, it is recommended to include a score system for malignancy (ADNEX MR/O-RADS) (Grade C) in the report and to formulate a histological hypothesis (Grade C). Pelvic MRI is recommended to characterize a tumor suspected of being a BOT (Grade C). Macroscopic MRI features should be analyzed to differentiate BOT subtypes (Grade C). Pelvic ultrasound is the first-line examination for the detection and characterization of adnexal masses during pregnancy (Grade C). Pelvic MRI is recommended from 12 weeks of gestation in case of an indeterminate adnexal mass and should provide a diagnostic score (Grade C). Gadolinium injection must be minimized as fetal impairment has been proven (Grade C). It is recommended that serum levels of HE4 and CA125 be evaluated and that the ROMA score for the diagnosis of an indeterminate ovarian mass on imaging be used (grade A). In case of suspicion of a mucinous BOT on imaging, dosage of serum levels of CA 19-9 can be considered (Grade C). If the determination of tumor markers is normal preoperatively, routine dosage of tumor markers in BOT follow-up is not recommended (Grade C). In case of preoperative elevation in tumor markers, the determination of serum CA 125 levels is recommended in the follow-up of BOT (Grade B). When conservative treatment of a BOT has been adopted, the use of endovaginal and transabdominal ultrasonography is recommended during follow-up (Grade B).

Lymphoepithelioma-like carcinoma of the ovary: a case report and review of the literature.

Lymphoepithelioma-like carcinoma (LELC), which is commonly reported in the nasopharynx and occasionally in other organs, remains a rare condition in gynecology. It is morphologically defined as a poorly differentiated carcinoma with prominent lymphoplasmacytic infiltrate. We present a case of an 82-year-old woman with a 10 cm LELC of the ovary shown by inguinal lymph nodes. There was no peritoneal carcinomatosis. Cytoreductive surgery was performed to remove a left ovarian neoplasm and multiple involved lymph nodes. Cytoreduction was complete. The tumor was a mixed poorly undifferentiated ovarian carcinoma consisting of 95% LELC and 5% moderately differentiated serous adenocarcinoma. Immunohistochemistry showed a large infiltration of T lymphocytes and plasma cells. Epstein-Barr virus was not detected by immunolabeling and polymerase chain reaction. The patient was still alive at 24 months of follow-up. To our knowledge, this is the second case of ovarian LELC and the first description of the native tumor before chemotherapy. In conclusion, this rare tumor of the ovary is difficult to diagnose both preoperatively and perioperatively. However, clinicians and pathologists should be aware that ovarian tumors with massive involvement of lymph nodes and no peritoneal carcinomatosis are suggestive of such a diagnosis and that prognosis is relatively good.