A Home-Mailed Versus General Practitioner-Delivered Vaginal Self-Sampling Kit for Cervical Cancer Screening: A Cluster Randomized Controlled Trial with a Cost-Effectiveness Analysis.

Objective: We assessed whether general practitioner (GP) delivery of a vaginal self-sampling kit was non-inferior to home-mailed delivery on cervical cancer screening (CCS) participation. Methods: Two hundred and ten French GPs from Indre-et-Loire French department were randomized into two groups, and their unscreened women patients aged 30-65 were included in February-March 2015. In the GP delivery group (n = 105 GPs; 1,806 women), women were sent a reminder letter inviting them to collect a vaginal self-sampling kit at their regular GP's practice. In the home-mailed delivery group (n = 105 GPs; 1,806 women), women were sent a reminder letter with a vaginal self-sampling kit directly at home. The primary outcome was participation in complete CCS within 9 months. A cost-effectiveness analysis was also performed. Results: At 9 months, 14.9% (95% CI: 12.9-16.9) and 27.9% (95% CI: 25.7-30.0) of women in the GP and home-mailed delivery groups participated in complete CCS. The absolute between-group difference was -13.0 percentage points (95% CI: -15.9 to -10.0) in favor of the home-mailed delivery group, crossing the non-inferiority pre-defined non-inferiority margin of 5%. The home-mailed delivery strategy cost 50.81€ more per additional woman screened. Conclusions: The GP delivery was inferior to home-mailed delivery in increasing participation in CCS. Home-mailed delivery of a vaginal self-sampling kit is a cost-effective way to increase CCS in that the additional cost of this strategy seems acceptable. This study is registered at www.Clinicaltrials.gov NCT02255084.

Long-term oncological safety of sentinel lymph node biopsy in early-stage cervical cancer: A post-hoc analysis of SENTICOL I and SENTICOL II cohorts.

OBJECTIVES: To compare oncologic outcomes of patients with early-stage cervical cancer and negative nodes who underwent sentinel lymph node biopsy alone (SLNB) versus pelvic lymphadenectomy (PL). METHODS: An ancillary analysis of two prospective multicentric trials on SLN biopsy for cervical cancer (SENTICOL I and II) was conducted. Only patients with early-stage cervical cancer (IA to IIA FIGO stage), bilateral detection of SLN, negative SLN after ultrastaging and negative non-SLN after final pathologic examination were included. Risk-factors of recurrence and disease-specific mortality were determined by Cox proportional hazard models. RESULTS: Between January 2005 and July 2012, 259 node-negative patients were analyzed: 87 in the SLNB group and 172 in the PL group. The median follow-up was 47 months [4-127]. During the follow-up, 21 patients (8.1%) experienced recurrences, including 4 nodal recurrences (1.9%), and 9 patients (3.5%) died of cervical cancer. Disease-free survival (DFS) and disease-specific survival (DSS) were similar between SLNB and PL groups, 85.1% vs. 80.4%, p = 0.24 and 90.8% vs. 97.2%, p = 0.22 respectively. By Cox multivariate analysis, SLNB compared to PL was not associated with DFS (HR = 1.78, 95%CI = [0.71-4.46], p = 0.22) neither with DSS (HR = 3.02, 95%CI = [0.69-13.18], p = 0.14). Only pathologic risk level according to the Sedlis criteria was an independent predictor of DFS and DSS. CONCLUSIONS: Omitting full pelvic lymphadenectomy for patients with bilateral negative SLN does not seem to be associated with an increased risk of recurrence in this series. Survival non-inferiority needs to be confirmed by prospective trials.

Ovarian arteries embolization in women with persistent symptoms following uterine arteries embolization for uterus fibroids.

PURPOSE: In patients with persisting symptoms after uterine arteries embolization (UAE), ovarian arteries embolization (OAE) may play a role to improve symptoms and decrease subsequent surgery rates. In a retrospective cohort, we aimed to investigate the efficacy and safety of OAE in females with recurrent or persistent symptoms following UAE. METHODS: We performed a retrospective analysis of prospectively collected cases at a single reference academic hospital; we identified patients who benefited from OAE for persisting symptoms following UAE from 2008 to 2021. Outcome variables included the rates of subsequent surgery, a quality-of-life questionnaire with the UFS-QOL tool, the MRI reduction in uterine and fibroids volumes and the fibroid devascularization rate. RESULTS: Among 1300 women treated with UAE during the study period, 18 eventually received OAE and were included (mean age 44 ± 4.3 SD). There was no OAE procedural complication. There was a decrease in uterine volume and a complete devascularization of the dominant fibroid in 10/11 (90.9%) patients who underwent 12 months MRI. Three women underwent subsequent hysterectomy. Among 10/18 patients who answered the quality-of-life questionnaire after a mean follow-up of 70 months, eight reported an improvement or stability of symptoms. CONCLUSION: OAE for persisting symptoms after UAE was associated with improvement or stability of quality-of-life in most study subjects and less than a fifth of the cohort underwent hysterectomy after OAE. This study highlights the role of OAE as an adjunct to UAE.

Experience implication in subjective surgical ergonomics comparison between laparoscopic and robot-assisted surgeries.

INTRODUCTION: Laparoscopic surgery (LS) may lead to musculoskeletal disorders (MSDs) and an increase in physical and mental workloads to the surgeon. Robot-assisted surgery (RAS) should improve the ergonomy of the surgeon. This study assesses the experience influence in surgical ergonomics between LS and RAS. METHODS: LS and RAS lasting more than 60 min of effective operative time were compared. During the surgical procedure, the physical discomfort was evaluated using the Borg scale. At the end, the mental workload was evaluated using the NASA-TLX index. After global analysis, the experienced and young surgeons were assessed. RESULTS: 88 RAS and 82 LS were evaluated. During LS, the physical discomfort was significantly higher in all segments, and the pain increased significantly during the procedure in all segments compared to that evaluated in the RAS (p < 0.05). Forearms and the back were the most painful. The young surgeons did not display any improvement in the physical ergonomics of the RAS compared to the LS. Concerning the mental ergonomics, the overall workload and performance were significantly greater during the LS compared to the RAS (p < 0.05). For the young surgeons, the overall workload, the effort, the mental and the physical demands were greater during LS (p < 0.05). For the experienced surgeons, the physical demand was lower during the RAS compared to the LS (p < 0.05). However, the experienced surgeons expressed a feeling of greater performance after the LS (p < 0.01). RAS significantly reduces the onset of MSDs compared to LS, especially for the experienced surgeons. CONCLUSION: RAS significantly reduces the onset of MSDs compared to LS, especially for the experienced surgeons.

Broad-Range Papillomavirus Transcriptome as a Biomarker of Papillomavirus-Associated Cervical High-Grade Cytology.

Human papillomaviruses (HPVs) are responsible for >99% of cervical cancers. Molecular diagnostic tests based on the detection of viral DNA or RNA have low positive predictive values for the identification of cancer or precancerous lesions. Triage with the Papanicolaou test lacks sensitivity; and even when combined with molecular detection of high-risk HPV, this results in a significant number of unnecessary colposcopies. We have developed a broad-range detection test of HPV transcripts to take a snapshot of the transcriptome of 16 high-risk or putative high-risk HPVs in cervical lesions (HPVs 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68, 73, and 82). The purpose of this novel molecular assay, named HPV RNA-Seq, is to detect and type HPV-positive samples and to determine a combination of HPV reads at certain specific viral spliced junctions that can better correlate with high-grade cytology, reflecting the presence of precancerous cells. In a proof-of-concept study conducted on 55 patients, starting from cervical smears, we have shown that HPV RNA-Seq can detect papillomaviruses with performances comparable to a widely used HPV reference molecular diagnostic kit; and a combination of the number of sequencing reads at specific early versus late HPV transcripts can be used as a marker of high-grade cytology, with encouraging diagnostic performances as a triage test.

Clinical practice guidelines for contraception by the French National College of Gynecologists and Obstetricians (CNGOF).

The French College of Obstetrics and Gynecology (CNGOF) has released its first comprehensive recommendations for clinical practices in contraception, to provide physicians with an updated synthesis of the available data as a basis for their practice. The organizing committee and the working group adopted the objective methodological principles defined by the French Authority for Health (HAS) and selected 12 themes relevant to medical professionals' clinical practices concerning contraception. The available literature was screened through December 2017 and served as the basis of 12 texts, reviewed by experts and physicians from public and private practices, with experience in this field. These texts enabled us to develop evidence based, graded recommendations. Male and female sterilization, as well as the use of hormonal treatments not authorized for contraception ("off-label") were excluded from the scope of our review. Specific practical recommendations are provided for the management of contraception prescription, patient information concerning effectiveness, risks, and benefits of the different methods, patient follow-up, intrauterine contraception, emergency contraception, local and natural methods, contraception in teenagers, in women after 40, for women at high thromboembolism or cardiovascular risk, and for those at of primary cancer or relapse. The short- and mid-term future of contraception depends mainly on improving the use of currently available methods. This includes reinforced information for users and increased access to contraception for women, regardless of their social and clinical contexts. The objective of these guidelines is to aid in enabling this improvement.

Intraoperative Factors that Predict the Successful Placement of Essure Microinserts.

STUDY OBJECTIVE: To determine whether the number of coils visualized in the uterotubal junction at the end of hysteroscopic microinsert placement predicts successful tubal occlusion. DESIGN: Cohort retrospective study (Canadian Task Force classification II-2). SETTING: Department of obstetrics and gynecology in a teaching hospital. PATIENTS: One hundred fifty-three women underwent tubal microinsert placement for permanent birth control from 2010 through 2014. The local institutional review board approved this study. INTERVENTION: Three-dimensional transvaginal ultrasound (3D TVU) was routinely performed 3 months after hysteroscopic microinsert placement to check position in the fallopian tube. MEASUREMENTS AND MAIN RESULTS: The correlation between the number of coils visible at the uterotubal junction at the end of the hysteroscopic microinsert placement procedure and the device position on the 3-month follow-up 3D TVU in 141 patients was evaluated. The analysis included 276 microinserts placed during hysteroscopy. The median number of coils visible after the hysteroscopic procedure was 4 (interquartile range, 3-5). Devices for 30 patients (21.3%) were incorrectly positioned according to the 3-month follow-up 3D TVU, and hysterosalpingography was recommended. In those patients the median number of coils was in both the right (interquartile range, 2-4) and left (interquartile range, 1-3) uterotubal junctions. The number of coils visible at the uterotubal junction at the end of the placement procedure was the only factor that predicted whether the microinsert was well positioned at the 3-month 3D TVU confirmation (odds ratio, .44; 95% confidence interval, .28-.63). When 5 or more coils were visible, no incorrectly placed microinsert could be seen on the follow-up 3D TVU; the negative predictive value was 100%. No pregnancies were reported. CONCLUSION: The number of coils observed at the uterotubal junction at the time of microinsert placement should be considered a significant predictive factor of accurate and successful microinsert placement.

Overview and guidelines of off-label use of methotrexate in ectopic pregnancy: report by CNGOF.

Our objective is to describe off-label use of methotrexate in ectopic pregnancy treatment using evidence based medicine. The patient group includes all women with a pregnancy outside the usual endometrium, or of unknown location. Method used was a Medline search on ectopic pregnancy managed using methotrexate treatment; evidence synthesis was done based on this current literature analysis. Level of evidence (LE) were given according to the centre for evidence base medicine rules. Grade was proposed for guidelines but no recommendation was possible as misoprostol is off label use for all the indications studied. In the absence of any contraindication, the protocol recommended for medical treatment of ectopic pregnancy is a single intramuscular injection of methotrexate (MTX) at a dosage of 1mg/kg or 50mg/m(2) (Grade A). It can be repeated once at the same dose should the hCG concentration not fall sufficiently. Pretreatment laboratory results must include a complete blood count and kidney and liver function tests (in accordance with its marketing authorization). MTX is an alternative to conservative treatment such as laparoscopic salpingotomy for uncomplicated tubal pregnancy (Grade A) with pretreatment hCG levels≤5000IU/l (Grade B). Expectant management is preferred for hCG levels<1000IU/l or in the process of spontaneous decreasing (Grade B). Intramuscular MTX is also recommended after the failure of surgical salpingotomy (Grade C) or immediately after surgery, if monitoring is not possible. Except in special circumstances, a local insitu ultrasound-guided MTX injection is not recommended for unruptured tubal pregnancies (Grade B). In situ MTX is an option for treating cervical, interstitial, or cesarean-scar pregnancies (Grade C). In pregnancies of unknown location persisting more than 10days in an asymptomatic woman who has an hCG level>2000IU/l, routine MTX treatment is an option. MTX is not indicated for combination with treatments such as mifepristone or potassium.

Contribution of lymphoscintigraphy to intraoperative sentinel lymph node detection in early cervical cancer: Analysis of the prospective multicenter SENTICOL cohort.

PURPOSE: To evaluate the contribution of preoperative lymphoscintigraphy to intraoperative lymphatic mapping (ILM) in early cervical cancer METHODS: We conducted an ancillary analysis of the multicenter prospective SENTICOL study in early cervical cancer. Radiocolloid was injected intracervically on the day before (long protocol) or morning of (short protocol) surgery, lymphoscintigraphy was performed, and the results of a centralized image review were communicated to the surgeons. ILM was performed on combined radioactivity/patent blue detection. Sentinel lymph nodes (SLNs) were electively sampled before routine bilateral pelvic lymphadenectomy by laparoscopy. RESULTS: Of 139 patients in the modified intention-to-diagnose analysis, 114 had centrally reviewed lymphoscintigrams, which showed 352 SLNs in 100 patients. Lymphoscintigraphy and ILM detection rates were 87.8% and 97.8%, respectively. Agreement between lymphoscintigraphy and ILM was low for the number of SLNs (κ=0.23; -0.04; 0.49) and bilateral SLNs (κ=0.36; 0.2; 0.52). No patient without SLNs by ILM had SLNs by lymphoscintigraphy. Lymphoscintigraphy identified substantial proportions of unusual drainage pathways. No patients with metastatic nodes had SLNs by lymphoscintigraphy but not by ILM in the relevant territory. In 1 of the 2 patients with false-negative SLN results, SLNs were bilateral by lymphoscintigraphy and unilateral by ILM. CONCLUSION: Although the detection rate was lower by lymphoscintigraphy than by ILM, the substantial proportions of SLNs in unusual territories provided valuable guidance for the surgical exploration. Awareness of the limited agreement between lymphoscintigraphic and surgical detection might help surgeons decrease the false-negative rate.

Sentinel node biopsy for the management of early stage endometrial cancer: long-term results of the SENTI-ENDO study.

OBJECTIVE: We report the long-term results of the SENTI-ENDO study evaluating the impact of sentinel lymph node (SLN) biopsy on management and survival in patients with early stages of endometrial cancer (EC). METHODS: Patients with FIGO stage I-II EC underwent pelvic SLN biopsy after cervical dual injection (technetium and patent blue) and systematic pelvic node dissection. This study is a secondary endpoint reporting the long-term recurrence free survival (RFS) and the impact of the SLN procedure on adjuvant therapies. RESULTS: The median follow-up was 50 months (range: 3-77 months). Eighteen of the 125 patients (14.4%) experienced a recurrence. The 50-month recurrence-free survival (RFS) was 84.7% with no difference between patients with and without detected SLN (p = 0.09). Among patients with detected SLN (111), no difference in RFS was observed between those with and without positive SLN (p = 0.5). In the whole population, adjuvant therapy was performed in low-, intermediate- and high-risk groups in 31 of 64 patients (48.4%), 28 of 37 patients (75.7%) and 14 of 17 patients (82.3%), respectively (p = 0.0001). For the 111 patients with detected SLN, EBRT was performed in 27 of the 89 with negative SLN and in 11 of the 14 with positive SLN (p = 0.001). Chemotherapy was performed more frequently in patients with positive SLN (6/12, 50%) than in patients with negative SLN (7/56, 12.5%) (p = 0.009). CONCLUSIONS: Our results support the impact of SLN biopsy on surgical management and indications for adjuvant therapies. Further studies are required to assess the clinical impact of the SLN biopsy in early stage EC.

Feasibility and performance of lymphoscintigraphy in sentinel lymph node biopsy for early cervical cancer: results of the prospective multicenter SENTICOL study.

OBJECTIVE: To evaluate feasibility, SLN detection rate, and SLN location of lymphoscintigraphy in sentinel lymph node (SLN) biopsy for early cervical cancer. METHODS: Ancillary analysis of data from the multicenter prospective SENTICOL study (January 2005-June 2007) of patients with early cervical cancer (FIGO stage IA with emboli to IB1) was conducted. Preoperative lymphoscintigraphy was performed after intracervical administration of 60 or 120 MBq of (99m)Tc-labeled radiocolloid on the day before (long protocol) or morning of (short protocol) surgery. SLNs were identified intraoperatively using combined radioactivity/patent blue detection. SLNs were sampled electively and routine bilateral pelvic lymphadenectomy was performed by laparoscopy. A centralized review of lymphoscintigraphies was performed to assess feasibility, detection rates, and anatomic SLN location. RESULTS: Of 139 patients included in the SENTICOL study, 133 received radiocolloid injection, and 131 (98.5 %) underwent preoperative lymphoscintigraphy, with the long protocol in three-fourths of cases. The lymphoscintigraphic detection rate was 87.8 %, with a median of 2 (1-4) SLNs per patient. By multivariate analysis, factors independently associated with lymphoscintigraphic SLN detection were age [odds ratio (OR) 0.91, 95 % confidence interval (95 % CI) 0.87-0.96; P < 0.001], and protocol (long vs. short; OR 8.23, 95 % CI 1.87-36.25; P = 0.005). Bilateral SLN identification by lymphoscintigraphy occurred in 67 % of cases and was independently influenced by age (OR 0.95, 95 % CI 0.92-0.98, P < 0.001) and protocol (OR 5.42, 95 % CI 2.21-13.27; P < 0.001). Although 60.5 % of preoperative SLNs were in the external iliac territory, unusual drainage patterns included the common iliac (19.6 %), para-aortic (10.8 %), and parametrial (6 %) basins. CONCLUSIONS: Our study demonstrates the feasibility and good detection rate of preoperative lymphoscintigraphy, with better detection in younger patients and with the long protocol. The high proportion of SLN basins in unexpected territories is of interest to guide intraoperative detection. Further studies are needed to better evaluate preoperative detection and to assess the contribution of lymphoscintigraphy to intraoperative detection.

[Men with breast cancer have increased risk of other cancers]. / Augmentation du risque de cancer extra-mammaire chez les hommes atteints de cancer du sein.

OBJECTIVE: To investigate the frequency of family history of breast cancer in male patients with breast cancer and the association with other cancers. PATIENTS AND METHODS: The patient group consisted of consecutive male patients managed for primary breast cancer in our institution between January 1997 and July 2012. Clinical data included comorbidities, BMI, personal and familial history of other cancers were searched. RESULTS: Thirty-one male patients with the diagnosis of 32 primary breast cancers were enrolled during the study period. Thirty-two percent patients had family history of breast cancer, 29% patients had other primary cancers, and 16.1% of patients had associated prostate cancer. DISCUSSION AND CONCLUSION: Male breast cancer frequently occurs in a context of family history of breast cancer. Its diagnosis must lead to the screening of prostate cancer especially in young men with family history.

Risk of incidental finding of endometrial cancer at the time of hysterectomy for benign condition.

STUDY OBJECTIVE: To assess the risk of unanticipated endometrial carcinoma during hysterectomy to treat a presumed benign condition. DESIGN: Retrospective analysis (Canadian Task Force classification II-2). SETTING: Tertiary referral center, university hospital. PATIENTS: All women who underwent hysterectomy to treat presumed benign indications at our center from January 2000 to December 2011 were identified. We analyzed all pathologic reports and identified cases of unexpected endometrial carcinoma. INTERVENTIONS: Hysterectomy by any approach to treat presumed benign indications. MEASUREMENTS AND MAIN RESULTS: At our institution, 2179 hysterectomies were performed to treat presumed benign indications. Nine (0.4%) revealed unexpected endometrial carcinoma (95% confidence interval, 0.2-0.7). CONCLUSION: Our data suggest that the rate of unanticipated endometrial carcinoma during hysterectomy to treat benign conditions is low.

Novel use of contrast-enhanced sonography in the diagnosis of central uterine necrosis following embolization for postpartum hemorrhage.

Since 2007, we have identified 2 cases of central uterine necrosis after uterine arterial embolization for postpartum hemorrhage. Contrast-enhanced sonography showed an absence of enhancement of the internal myometrium. Magnetic resonance imaging with gadolinium confirmed the diagnosis. The images obtained for the first case were corroborated by histologic analysis from a hysterectomy done for sepsis. For the second case, contrast-enhanced sonography performed during a follow-up period of conservative treatment revealed a reduction of necrosis. Our study shows that contrast-enhanced sonography seems to be a useful examination as an adjunct to grayscale and power Doppler imaging in the diagnosis and follow-up of uterine necrosis.

[Uterine artery embolization for myomas treatment]. / Embolisation dans le traitement des myomes.

Myoma treatment by uterine artery embolisation (UAE) using non-spherical PVA particles or calibrated tris-acryl microspheres>500µm is effective in more than 90 % of cases in the short-term. In the long-term, menorrhagia, bulk-related symptoms and pelvic pain are significantly improved or eliminated in 75 % of cases at 5 to 7 years. At 6 months, uterine volume reduction and larger myoma volume reduction varies between 30 to 60 % and 50 to 80 % respectively. During hospital stay the complication rate is very low, less than 3 % mostly urinary infection and pain. Secondary hysterectomy for complication is less than 2 % at 3 months. Definitive amenorrhea is reported in less than 5 % of cases in women of more than 45-year of age. No significant impact of embolization on hormonal function has been reported in women less than 45 years with normal baseline function. UAE is not indicated for submucous myomas. Randomized studies comparing embolization to hysterectomy demonstrate that reinterventions are more frequently performed after embolization. Secondary hysterectomy is performed in 13 to 24 % of cases at 2 years and in up to 28 % of cases at 5 years. Hospital stay, duration of recovery and time off work are shorter after embolization compared to hysterectomy. Embolization is cheaper than hysterectomy at 12 and 24 months even taking into consideration the additional costs of imaging and reinterventions. UAE is a good alternative treatment in women with unique myoma of less than 10cm and multiple myomas around 15cm. This treatment should be proposed to women each time possible. Randomized studies comparing embolization to myomectomy demonstrate that in the short and mid-term there is no difference in terms of control of menorrhagia and bulk-related symptoms. Uterine volume reduction and quality of life were not different at 6 months. Periprocedural and 30-day complication rates are not different. At 6 months, the rate of complications is higher after myomectomy. Reinterventions are more frequent after embolization compared to myomectomy. Hospital stay, duration of recovery and time off work are shorter after embolization compared to myomectomy. UAE is less aggressive than myomectomy and should be proposed as a conservative alternative treatment. Embolization should be considered with caution in pregnancy-seeking women since there is still a lack of good quality data available in the specific group of patients. FSH level is more frequently elevated after embolization compared to myomectomy. Pregnancy rate and term pregnancy rate are higher after myomectomy compared to embolization. Spontaneous abortion is more frequent after embolization than after myomectomy. At this time, UAE is not indicated excepted in studies or in specific cases when the woman want a pregnancy. Embolization performed before myomectomy (preoperative or combined procedures) can be discussed for an individual patient but there is not enough data to support its routine use.

Validation of a breast cancer nomogram for predicting nonsentinel node metastases after minimal sentinel node involvement: validation of the Helsinki breast nomogram.

BACKGROUND: Complete node dissection for tumor-positive sentinel lymph nodes (SLN) is becoming more controversial. Nevertheless, current practice guidelines still recommend complete axillary lymph node dissection (ALND) for breast cancer patients whose SLN contains a metastatic tumor. The Helsinki breast cancer nomogram developed by Meretoja TJ et al. aims to predict the risk of positive non-sentinel lymph nodes in patients with minimal sentinel node involvement, it uses tumor diameter and multifocality. The purpose of this study was to test the accuracy of the nomogram among patients with micrometastatic SLN-positive biopsy findings. METHODS: The Helsinki nomogram was used to calculate risk of metastases for 49 consecutive patients with SLN micrometastases or isolated tumor cells (ITC) who underwent complete ALND. The nomogram was evaluated by calculating the area under the receiver-operator characteristic (ROC) curve. RESULTS: The area under the ROC curve for the nomogram applied to all patients with micrometastases and ITC was 0.72 (range 0.60-0.85) (0.791 in the original publication). CONCLUSIONS: The Helsinki breast cancer nomogram is a useful tool for patients with minimal sentinel node involvement.