Reviving peritoneal cytology: Exploring its role in endometrial cancer molecular classification.

OBJECTIVE: The prognostic significance of positive peritoneal cytology in endometrial cancer has long been debated. In 2009, the Fédération Internationale de Gynécologie et d'Obstétrique (FIGO) removed cytology as a staging criterion from the endometrial cancer staging system. However, there is still evidence that positive peritoneal cytology may decrease survival among patients with endometrial cancer. The aim of this study was to determine the prognostic significance of positive peritoneal cytology among the different molecular subgroups. METHODS: This study included patients with endometrial cancer who underwent primary surgical treatment between 2004 and 2015 at the Bern University Hospital, Switzerland, with molecular classification of the primary tumor and peritoneal cytology performed. RESULTS: A total, 250 patients with endometrial cancer were enrolled. Peritoneal cytology was assessed in 206 patients, of whom 24% were positive: 25% of the POLEmut, 16% of the MMRd, 41% of the p53abn, and 24% of the NSMP cases. The mean follow-up was 128.7 months. Presence of positive peritoneal cytology was associated with significantly decreased mean recurrence-free and overall survival in patients with p53abn (p = .003 and p = .001) and NSMP (p = .020 and p = .049) endometrial cancer. In multivariable Cox regression analysis, positive peritoneal cytology remained an independent predictor of recurrence (p = .033) and death (p = .008) in p53abn endometrial cancer patients. CONCLUSION: Positive peritoneal cytology is associated with worse oncologic outcomes in NSMP and p53abn endometrial cancer and remains an independent predictor of recurrence and death in patients with p53abn endometrial cancer.

Consensus on surgical technique for sentinel lymph node dissection in cervical cancer.

OBJECTIVE: The purpose of this study was to establish a consensus on the surgical technique for sentinel lymph node (SLN) dissection in cervical cancer. METHODS: A 26 question survey was emailed to international expert gynecological oncology surgeons. A two-step modified Delphi method was used to establish consensus. After a first round of online survey, the questions were amended and a second round, along with semistructured interviews was performed. Consensus was defined using a 70% cut-off for agreement. RESULTS: Twenty-five of 38 (65.8%) experts responded to the first and second rounds of the online survey. Agreement ≥70% was reached for 13 (50.0%) questions in the first round and for 15 (57.7%) in the final round. Consensus agreement identified 15 recommended, three optional, and five not recommended steps. Experts agreed on the following recommended procedures: use of indocyanine green as a tracer; superficial (with or without deep) injection at 3 and 9 o'clock; injection at the margins of uninvolved mucosa avoiding vaginal fornices; grasping the cervix with forceps only in part of the cervix is free of tumor; use of a minimally invasive approach for SLN biopsy in the case of simple trachelectomy/conization; identification of the ureter, obliterated umbilical artery, and external iliac vessels before SLN excision; commencing the dissection at the level of the uterine artery and continuing laterally; and completing dissection in one hemi-pelvis before proceeding to the contralateral side. Consensus was also reached in recommending against injection at 6 and 12 o'clock, and injection directly into the tumor in cases of the tumor completely replacing the cervix; against removal of nodes through port without protective maneuvers; absence of an ultrastaging protocol; and against modifying tracer concentration at the time of re-injection after mapping failure. CONCLUSION: Recommended, optional, and not recommended steps of SLN dissection in cervical cancer have been identified based on consensus among international experts. These represent a surgical guide that may be used by surgeons in clinical trials and for quality assurance in routine practice.

Change of Fagotti score is associated with outcome after neoadjuvant chemotherapy for ovarian cancer.

OBJECTIVE: To investigate whether a change in the Fagotti score (ΔFagotti) following neoadjuvant chemotherapy is predictive of resection to no residual disease (R0) and survival in women diagnosed with ovarian cancer. METHODS: Women treated with neoadjuvant chemotherapy for newly diagnosed ovarian cancer between January 2012 and June 2021 at the Bern University Hospital were included in this retrospective cohort study. Fagotti scores before and after neoadjuvant chemotherapy treatment were assessed for a potential association with resection status at interval debulking surgery defined as no residual disease (R0), macroscopic residual disease with a diameter of 0.1-1 cm (R1) or >1 cm (R2), and survival. RESULTS: During the study period, 130 patients received neoadjuvant chemotherapy, mainly in response to advanced ovarian cancer International Federation of Gynecology and Obstetrics (FIGO) stages IIIC (68.5%) or IV (20.8%). 91 patients (70%) experienced a relapse and 81 (62%) died due to their disease. Median overall survival was 40 months (95% CI 30.6 to 49.4). Fagotti scores dropped from a mean of 7.8 (95% CI 7.14 to 8.42) at diagnosis to 3.9 (95% CI 3.34 to 4.46, p<0.001) after neoadjuvant therapy. This decrease was associated with resection status during interval debulking surgery (mean ΔFagotti -4.9 in R0, -2.2 in R1, -0.6 in R2, p<0.001). Women whose Fagotti score declined more than 2 points after neoadjuvant chemotherapy (n=51/88, 58%) survived significantly longer (median overall survival of 42 vs 32 months, p=0.048). CONCLUSION: Fagotti scores and ΔFagotti scores are associated with complete cytoreduction at interval debulking surgery and longer overall survival in women treated with neoadjuvant chemotherapy for ovarian cancer. These markers are valuable for individualized patient treatment planning and should always be performed after neoadjuvant therapy.

Prognostic value of lymphovascular space invasion according to the molecular subgroups in endometrial cancer.

OBJECTIVE: Lymphovascular space invasion (LVSI) is a known prognostic factor for oncological outcome in endometrial cancer patients. However, little is known about the prognostic value of LVSI among the different molecular subgroups. The aim of this study was to determine the prognostic dependence of LVSI from the molecular signature. METHODS: This study included endometrial cancer patients who underwent primary surgical treatment between February 2004 and February 2016 at the Karolinska University Hospital, Sweden and the Bern University Hospital, Switzerland (KImBer cohort). All cases had complete molecular analysis performed on the primary tumor according to the WHO Classification of Tumors, 5th edition. LVSI was reviewed by reference pathologists for all pathology slides. RESULTS: A total of 589 endometrial cancer patients were included in this study, consisting of 40 POLEmut (polymerase epsilon ultramutated), 198 MMRd (mismatch repair deficient), 83 p53abn (p53 abnormal), and 268 NSMP (non-specific molecular profile) cases. Altogether, 17% of tumors showed LVSI: 25% of the POLEmut, 19% of the MMRd, 30% of the p53abn, and 10% of the NSMP cases. There was a significant correlation of LVSI with lymph node metastasis in the entire study cohort (p<0.001), remaining significant in the MMRd (p=0.020), p53abn (p<0.001), and NSMP (p<0.001) subgroups. Mean follow-up was 89 months (95% CI 86 to 93). The presence of LVSI significantly decreased recurrence-free survival among patients with MMRd, p53abn, and NSMP endometrial cancer, and overall survival in patients with p53abn and NSMP tumors. In patients with NSMP endometrial cancer, evidence of substantial LVSI remained a significant independent predictor of recurrence in multivariable Cox regression analysis including tumor stage and grade (HR 7.5, 95% CI 2.2 to 25.5, p=o.001). CONCLUSION: The presence of LVSI was associated with recurrence in each subgroup of patients with MMRd, p53abn, and NSMP endometrial cancer, and LVSI remained an independent predictor of recurrence in NSMP endometrial cancer patients.

Laparoscopic sacrocolpopexy mesh excision step-by-step.

INTRODUCTION AND HYPOTHESIS: The objective was to demonstrate the surgical procedure of laparoscopic mesh removal after sacrocolpopexy to aid clinicians facing mesh complications. METHODS: Video footage shows the laparoscopic management of mesh failure and mesh erosion after sacrocolpopexy with narrated video sequences of two patients. RESULTS: Laparoscopic sacrocolpopexy represents the gold standard in advanced prolapse repair. Mesh complications occur infrequently but infections, failure of prolapse repair and mesh erosions necessitate mesh removal and repeat sacrocolpopexy if applicable. The video deals with two women referred to our tertiary referral urogynecology unit in the University Women's Hospital of Bern, Switzerland, after laparoscopic sacrocolpopexies that were carried out in remote hospitals. Both patients were asymptomatic more than 1 year after surgery. CONCLUSIONS: Complete mesh removal after sacrocolpopexy and repeat prolapse surgery can be challenging but is feasible and is aimed at improving patients' complaints and symptoms.

True Prevalence of Diaphragmatic Endometriosis and Its Association with Severe Endometriosis: A Call for Awareness and Investigation.

STUDY OBJECTIVE: To identify characteristics indicating preoperatively the presence of diaphragmatic endometriosis (DE). DESIGN: Comparison of characteristics of patients with diaphragmatic endometriosis (DE) with characteristics of patients with abdominal endometriosis without diaphragmatic involvement, in a prospective cohort study. SETTING: Tertiary referral center; endometriosis center. PATIENTS: A total of 1372 patients with histologically proven endometriosis. INTERVENTIONS: Surgery performed laparoscopically under general anesthesia. All patients with suspected endometriosis underwent a complete bilateral inspection of the diaphragm. MEASUREMENTS AND MAIN RESULTS: Demographic and clinical pathologic characteristics were evaluated using basic descriptive statistics (comparison of the groups using the χ2 test and the Mann-Whitney t test). A logistic regression analysis was performed to evaluate the relationship (hazard ratio) between symptoms and the presence of DE. DE was diagnosed in 4.7% of the patients (65 of 1372). There was no significant difference between the 2 groups (patients with abdominal endometriosis with or without DE) with regard to typical endometriosis pain (dysmenorrhea, dyschezia, dysuria, and/or dyspareunia). However, in the DE group, diaphragmatic pain was present significantly more often preoperatively (27.7% vs 1.8%, p <.001). Four DE patients (6.1 %) were asymptomatic (with infertility the indication for surgery). In the DE group, 78.4 % had advanced stages of endometriosis (revised American Fertility Society III° or IV°); the left lower pelvis was affected in more patients (73.8%). In cases of ovarian endometriosis, patients with DE showed a significantly higher prevalence of left ovaries involvement (left 63% vs right 35.7%, p <.001). Patients with DE had a significantly higher rate of infertility (49.2% vs 28.7%, p <.05). CONCLUSION: Patients with shoulder pain, infertility, and/or endometriosis in the left pelvis have a significant higher risk of DE and therefore need specific preoperative counseling and if indicated surgical treatment.

Prospective Multicenter Trial Assessing the Impact of Positive Peritoneal Cytology Conversion on Oncological Outcome in Patients with Endometrial Cancer Undergoing Minimally Invasive Surgery with the use of an Intrauterine Manipulator : Positive Peritoneal Cytology Conversion and Its Association with Oncological Outcome in Endometrial Cancer.

BACKGROUND: Minimally invasive surgery is the standard approach in early-stage endometrial cancer according to evidence showing no compromise in oncological outcomes, but lower morbidity compared with open surgery. However, there are limited data available on the oncological safety of the use of intrauterine manipulators in endometrial cancer. PATIENTS AND METHODS: This prospective multicenter study included patients with endometrial cancer undergoing laparoscopic staging surgery with the use of an intrauterine manipulator. We obtained three different sets of peritoneal washings: at the beginning of the surgical procedure, after the insertion of the intrauterine manipulator, and after the closure of the vaginal vault. The rate of positive peritoneal cytology conversion and its association with oncological outcomes was assessed. RESULTS: A total of 124 patients were included. Peritoneal cytology was negative in 98 (group 1) and positive in 26 (group 2) patients. In group 2, 16 patients presented with positive cytology at the beginning of the surgery (group 2a) and 10 patients had positive cytology conversion during the procedure (group 2b). Recurrence rate was significantly different among the study groups, amounting to 9.2%, 25.0%, and 60.0% for groups 1, 2a, and 2b, respectively (p < 0.001). Group 1 showed the best recurrence-free and overall survival, followed by group 2a, while patients in group 2b had the worst oncological outcomes (p = 0.002 and p = 0.053, respectively). Peritoneal cytology was an independent predictor of recurrence and death on multivariable analysis. CONCLUSION: A total of 8.1% of patients with endometrial cancer undergoing minimally invasive surgery with intrauterine manipulation showed positive peritoneal cytology conversion associated with significantly worse oncological outcome.

Evaluating long-term outcomes of three approaches to retroperitoneal staging in endometrial cancer.

OBJECTIVE: Sentinel lymph node mapping (SNM) has gained popularity in managing apparent early-stage endometrial cancer (EC). Here, we evaluated the long-term survival of three different approaches of nodal assessment. METHODS: This is a multi-institutional retrospective study evaluating long-term outcomes of EC patients having nodal assessment between 01/01/2006 and 12/31/2016. In order to reduce possible confounding factors, we applied a propensity-matched algorithm. RESULTS: Overall, 940 patients meeting inclusion criteria were included in the study, of which 174 (18.5%), 187 (19.9%), and 579 (61.6%) underwent SNM, SNM followed by backup lymphadenectomy (LND) and LND alone, respectively. Applying a propensity score matching algorithm (1:1:2) we selected 500 patients, including 125 SNM, 125 SNM/backup LND, and 250 LND. Baseline characteristics of the study population were similar between groups. The prevalence of nodal disease was 14%, 16%, and 12% in patients having SNM, SNM/backup LND and LND, respectively. Overall, 19 (7.6%) patients were diagnosed with low volume nodal disease. The survival analysis comparing the three techniques did not show statistical differences in terms of disease-free (p = 0.750) and overall survival (p = 0.899). Similarly, the type of nodal assessment did not impact survival outcomes after stratification based on uterine risk factors. CONCLUSION: Our study highlighted that SNM provides similar long-term oncologic outcomes than LND.

Parallel targeted and non-targeted quantitative analysis of steroids in human serum and peritoneal fluid by liquid chromatography high-resolution mass spectrometry.

We developed and validated a liquid chromatography high-resolution mass spectrometry method for the absolute quantification of 51 steroids for clinical analysis of human serum and, for the first time, peritoneal fluid. Data acquisition was performed in both targeted and untargeted mode simultaneously, thus allowing the accurate and precise quantification of the main components of the classical steroid pathways (17 steroids) as well as the analysis of 34 additional non-classical steroids. For targeted analysis, validation was performed according to FDA guidelines, resulting, among other parameters, in accuracy < 13% RSD and precision < 10% relative error, for both inter- and intra-day validation runs. By establishing steroid-specific response factors, the calibration curves of the targeted analytes can be extended to untargeted analytes. This approach opens novel possibilities for the post hoc analysis of clinical samples as the data can be examined for virtually any steroid even after data acquisition, enabling facile absolute quantification once a standard becomes available. We demonstrate the applicability of the approach to evaluate the differences in steroid content between peripheral serum and peritoneal fluid across the menstrual cycle phases, as well as the effect of the synthetic gestagen dienogest on the steroid metabolome.

Postpartum urinary retention: what are the sequelae? A long-term study and review of the literature.

INTRODUCTION AND HYPOTHESIS: Postpartum urinary retention (PUR) may cause long-term urogenital tract morbidity. The incidence ranges from 0.18 to 14.6%, but the importance of prompt diagnosis and appropriate management is often underappreciated. The paucity of data on long-term outcome after PUR contributes to these drawbacks. The aim of this study was to assess long-term persistence of elevated PVR (post-void residual urine) volume after PUR. Pathophysiology, risk factors and management of PUR are reviewed. METHODS: In our tertiary referral urogynecology unit in the University Women's Hospital of Bern, Switzerland, all patients who were referred for PUR were asked to participate in this study. PVR was measured sonographically every 2 days until day 15, then after 6, 12, 24 and 36 months and, if increased, the patients were instructed to perform clean intermittent self-catheterization. If retention persisted longer than the lactation period, multichannel urodynamics was performed. RESULTS: Sixty-two patients were included. The median PVR normalized at day 7. Long-term voiding disorders were found in 8.2%, 6.7%, and 4.9% after 1, 2, and 3 years respectively. Multichannel urodynamics confirmed in all patients with persisting retention an acontractile detrusor and de novo stress urinary incontinence in 4 cases. Quantile regression did not reveal any factor contributing to earlier recovery. Eighty-nine percent of the patients with PUR had operative vaginal deliveries, emphasizing the importance of this risk factor for PUR. CONCLUSIONS: In most cases PUR resolves early, but voiding difficulties persist more often than previously thought, and for these patients the consequences are devastating. Obstetric awareness, early active management, and developing management strategies in the postpartum period might preclude lower urinary tract morbidity.

Implementation of the 2021 molecular ESGO/ESTRO/ESP risk groups in endometrial cancer.

INTRODUCTION: In 2021, a joint ESGO/ESTRO/ESP committee updated their evidence-based guidelines for endometrial cancer, recommending a new risk grouping incorporating both clinicopathologic and molecular parameters. We applied the new risk grouping and compared the results to those of the prior 2016 clinicopathologic system. MATERIALS AND METHODS: We classified molecularly a cohort of 604 women diagnosed with endometrial cancer using immunohistochemistry for TP53 and MMR proteins on a tissue microarray, as well as Sanger sequencing for POLE mutations. These results, combined with clinicopathologic data, allowed the patients to be risk grouped using both the new 2021 molecular/clinicopathologic parameters and the prior 2016 clinicopathologic system. RESULTS: The application of the 2021 molecular markers shows Kaplan-Meier curves with a significant difference between the groups for all survival. Molecular classification under the 2021 guidelines revealed a total of 39 patients (39/594, 7%) with a change in risk group in relation to the 2016 classification system: the shift was alone due to either P53abn or POLEmut molecular marker. In order to ensure correct 2021 molecular risk classification, not all patients with endometrial cancer need a molecular diagnostic: 433 (72.9%) cases would need to be analyzed by TP53 IHC, only 46 (7.7%) by MMR IHC and 286 (48.1%) POLE sequencing reactions. CONCLUSION: Application of the 2021 molecular risk groups is feasible and shows significant differences in survival. IHC for TP53 and MMR and applying POLE sequencing is only needed in selected cases and leads to shifting risk groups both upward and downward for a sizeable number of patients. It is possible to significantly reduce the number of analyses required to implement the classification if resources are limited.

Sentinel node mapping vs. sentinel node mapping plus back-up lymphadenectomy in high-risk endometrial cancer patients: Results from a multi-institutional study.

OBJECTIVE: Sentinel node mapping (SLN) has replaced lymphadenectomy for staging surgery in apparent early-stage low and intermediate risk endometrial cancer (EC). Only limited data about the adoption of SNM in high risk EC is still available. Here, we evaluate the outcomes of high-risk EC undergoing SNM (with or without back-up lymphadenectomy). METHODS: This is a multi-institutional international retrospective study, evaluating data of high-risk (FIGO grade 3 endometrioid EC with myometrial invasion >50% and non-endometrioid histology) EC patients undergoing SNM followed by back-up lymphadenectomy and SNM alone. RESULTS: Chart of consecutive 196 patients were evaluated. The study population included 83 and 113 patients with endometrioid and non-endometrioid EC, respectively. SNM alone and SNM followed by back-up lymphadenectomy were performed in 50 and 146 patients, respectively. Among patients having SNM alone, 14 (28%) were diagnosed with nodal disease. In the group of patients undergoing SNM plus back-up lymphadenectomy 34 (23.2%) were diagnosed with nodal disease via SNM. Back-up lymphadenectomy identified 2 (1%) additional patients with nodal disease (in the para-aortic area). Back-up lymphadenectomy allowed to remove adjunctive positive nodes in 16 (11%) patients. After the adoption of propensity-matched algorithm, we observed that patients undergoing SNM plus back-up lymphadenectomy experienced similar disease-free survival (p = 0.416, log-rank test) and overall survival (p = 0.940, log-rank test) than patients undergoing SLN alone. CONCLUSIONS: Although the small sample size, and the retrospective study design this study highlighted that type of nodal assessment did not impact survival outcomes in high-risk EC. Theoretically, back-up lymphadenectomy would be useful in improving the removal of positive nodes, but its therapeutic value remains controversial. Further prospective evidence is needed.

Fertility, pregnancy and neonatal outcomes of patients with adenomyosis: a systematic review and meta-analysis.

This study aimed to investigate the association of adenomyosis with fertility, pregnancy and neonatal outcomes. An electronic search was conducted using the MEDLINE, PubMed and Cochrane databases up to April 2020. Seventeen observational studies were included. Adenomyosis was significantly associated with a lower clinical pregnancy rate (odds ratio [OR] 0.69; 95% confidence interval [CI] 0.51-0.94) and higher miscarriage rate (OR 2.17; 95% CI 1.25-3.79) after treatment with assisted reproductive technology (ART). The lower clinical pregnancy rate was more significant in the subgroup of patients with short down-regulation protocols. Similar associations were recorded after age adjustment. Adenomyosis was also significantly associated with an increased risk of pre-eclampsia, preterm delivery, Caesarean section, fetal malpresentation, small for gestational age infancy and post-partum haemorrhage, which was confirmed after correction for age and mode of conception. In conclusion, adenomyosis is associated with negative effects on fertility after ART. The potentially protective role of the ultra-long down-regulation protocols needs further evaluation in randomized controlled studies. Adenomyosis is also associated (independently of the mode of conception) with adverse pregnancy and neonatal outcomes. Proper counselling prior to ART and close monitoring of pregnancy in patients with adenomyosis should be recommended.

Impact of clinical factors and surgical outcome on long-term survival in high-grade serous ovarian cancer: a multicenter analysis.

INTRODUCTION: Long-term survivors of ovarian cancer are a unique group of patients in whom prognostic factors for long-term survival have been poorly described. Such factors may provide information for a more personalized therapeutic approach. The objective of this study is to determine further characteristics of long-term survivors with high-grade serous ovarian cancer. METHODS: Long-term survivors were defined as patients living longer than 8 years after first diagnosis and were recruited within seven high volume centers across Europe from November 1988 to November 2008. The control group included patients with high-grade serous ovarian cancer with less than 5 years' survival identified from the systematic 'Tumorbank ovarian cancer' database. A subanalysis of Charité patients only was performed separately for in-depth analysis of tumor dissemination. Propensity score matching with nearest-neighbor caliper width was used to match long-term survivors and the control group regarding age, FIGO stage, and residual tumor. RESULTS: A total of 276 patients with high-grade serous ovarian cancer were included, divided into 131 long-term survivors and 145 control group patients. After propensity score matching and multivariable adjustment, platinum sensitivity (p=0.002) was an independent favorable prognostic factor whereas recurrence (p<0.001) and ascites (p=0.021) were independent detrimental predictors for long-term survival. Significantly more long-term survivors tested positive for mutation in the BRCA1 gene than the BRCA2 gene (p=0.016). Intraoperatively, these patients had less tumor involvement of the upper abdomen at initial surgery (p=0.024). Complexity of surgery and surgical techniques were similar in both cohorts. CONCLUSION: Platinum sensitivity constitutes a favorable factor for long-term survival whereas tumor involvement of the upper abdomen, ascites, and recurrence have a negative impact. Based on clinical estimation, long-term survival is associated with combinations of clinical, surgical, and molecular factors.

Risk factors for non-response and discontinuation of Dienogest in endometriosis patients: A cohort study.

INTRODUCTION: Progestins are commonly prescribed first-line drugs for endometriosis. High rates of non-response and intolerance to these drugs have been previously reported. However, no study to date has investigated the characteristics and comorbidities of patients taking progestins in relation to treatment outcomes, so identifying which patients will respond to or tolerate the treatment is currently impossible. The purpose of this study, therefore, was to identify risk factors for non-response and discontinuation of Dienogest (DNG) in women with endometriosis. MATERIAL AND METHODS: This is a retrospective cohort study including women currently taking, or newly prescribed, DNG for endometriosis-associated pain presenting in the Endometriosis Clinic of the University Hospital of Bern between January 2017 and May 2018. Women with initiation of treatment directly after surgery for endometriosis were excluded. For all participants the symptoms and comorbidities were documented. Effectiveness, tolerability and discontinuation of DNG were the primary end points. Univariate and multivariate binary logistic regression models were carried out to identify risk factors for non-response, intolerance and discontinuation of DNG. RESULTS: A sufficient or excellent treatment response was reported by 85/125 (68%) participants. Genital bleeding during the DNG treatment was negatively (OR 0.185, 95% CI 0.056-0.610, P = .006) and rASRM endometriosis stages III and IV were positively (OR 3.876, 95% CI 1.202-12.498, P = .023) correlated with the DNG response. When accounting for exclusively pretreatment factors, primary dysmenorrhea (OR 0.236, 95% CI 0.090-0.615, P = .003) and suspicion of adenomyosis (OR 0.347, 95% CI 0.135-0.894, P = .028) were inversely correlated with DNG response, and the latter was also correlated with treatment discontinuation (OR 3.189, 95% CI 1.247-8.153, P = .015). CONCLUSIONS: Genital bleeding during the DNG treatment and low rASRM stages are independent risk factors for DNG non-response. Before treatment initiation, primary dysmenorrhea and suspicion of adenomyosis correlate with DNG non-response. The results could assist the clinician first to provide detailed information to women before treatment initiation, second to identify and possibly modify in-therapy factors correlated to treatment effectiveness and lastly to switch treatment on time if needed.

Predictive Factors for Voiding Dysfunction after Surgery for Deep Infiltrating Endometriosis.

STUDY OBJECTIVE: To evaluate the prognostic value of pre- and perioperative factors for voiding dysfunction after surgery for deep infiltrating endometriosis (DIE). DESIGN: Single-center retrospective cohort study. SETTING: University hospital. PATIENTS: A total of 198 women with DIE in the posterior compartment who underwent surgery and a postoperative bladder scan. INTERVENTIONS: Surgical resection of the DIE nodule from the dorsal compartment. MEASUREMENTS AND MAIN RESULTS: After surgery, 41% of the patients initially experienced voiding dysfunction (defined as >100 mL postvoid residual urine volume at second bladder scan). The number decreased to 11% by the time of hospital discharge. Among those with a need for self-catheterization after discharge (n = 17), voiding dysfunction lasted for a median of 41 days before a return to normal bladder function, with a residual urine volume of <100 mL. The preoperative presence of DIE nodules in the ENZIAN compartment B was associated with postoperative voiding dysfunction (p = .001). The hazard ratio for elevated residual urine volume was highest when the disease stage was B3 (hazard ratio 6.43; CI, 2.3-18.2; p <.001), describing a nodule diameter of >3 cm in lateral distension. Receiver operating characteristic curve analyses showed that a first residual urine volume >220 mL has a good predictive value for the risk of intermittent self-catheterization (area under the receiver operating characteristic curve 0.893; p <.001). CONCLUSION: Postoperative voiding dysfunction is frequent; of note, in most cases the problem is temporary. When DIE with an ENZIAN classification B is noted intraoperatively and, most of all, when the diameter of the lesion is >3 cm, a higher risk of postoperative voiding dysfunction is to be expected.

Anatomy of the female pelvic nerves: a macroscopic study of the hypogastric plexus and their relations and variations.

The autonomic nerves of the lesser pelvis are particularly prone to iatrogenic lesions due to their exposed position during manifold surgical interventions. Nevertheless, the cause of rectal and urinary incontinence or sexual dysfunctions, for example after rectal cancer resection or hysterectomy, remains largely understudied, particularly with regard to the female pelvic autonomic plexuses. This study focused on the macroscopic description of the superior hypogastric plexus, hypogastric nerves, inferior hypogastric plexus, the parasympathetic pelvic splanchnic nerves and the sympathetic fibres. Their arrangement is described in relation to commonly used surgical landmarks such as the sacral promontory, ureters, uterosacral ligaments, uterine and rectal blood vessels. Thirty-one embalmed female pelvises from 20 formalin-fixed and 11 Thiel-fixed cadavers were prepared. In all cases explored, the superior hypogastric plexus was situated anterior to the bifurcation of the abdominal aorta. In 60% of specimens, it reached the sacral promontory, whereas in 40% of specimens, it continued across the pelvic brim until S1. In about 25% of the subjects, we detected an accessory hypogastric nerve, which has not been systematically described so far. It originated medially from the inferior margin of the superior hypogastric plexus and continued medially into the presacral space. The existence of an accessory hypogastric nerve was confirmed during laparoscopy and by histological examination. The inferior hypogastric plexuses formed fan-shaped plexiform structures at the end of both hypogastric nerves, exactly at the junction of the ureter and the posterior wall of the uterine artery at the uterosacral ligament. In addition to the pelvic splanchnic nerves from S2-S4, which joined the inferior hypogastric plexus, 18% of the specimens in the present study revealed an additional pelvic splanchnic nerve originating from the S1 sacral root. In general, form, breadth and alignment of the autonomic nerves displayed large individual variations, which could also have a clinical impact on the postoperative function of the pelvic organs. The study serves as a basis for future investigations on the autonomic innervation of the female pelvic organs.

Visualization of endometriosis with laparoscopy and near-infrared optics with indocyanine green.

INTRODUCTION: Endometriosis is a common health problem, affecting 10% of women of reproductive age. Laparoscopic surgery is proven to relieve pain and to improve fertility in women with endometriosis. However, identifying peritoneal endometriosis lesions may be difficult due to their polymorphic aspects. Endometriosis lesions harbor a high degree of neovascularization. The visualization of tissue perfusion by the additional use of near infrared fluorescence imaging with indocyanine green (ICG) may improve the detection of endometriosis lesions. MATERIAL AND METHODS: In a single-center, prospective, single-arm pilot study, patients undergoing laparoscopic surgery for suspected endometriosis and/or infertility were recruited. All patients first had white light imaging with systematical documentation of all suspicious areas. ICG was then administered intravenously at .3 mg/kg bodyweight and the near infrared imaging was activated and an identical documentation of suspected lesions was performed again. After removal, the specimen were sent to pathology. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov NCT03850158. RESULTS: In total, 173 suspected lesions were identified and excised, of which 150 had histologically proven endometriosis. Of the total number, 166 suspected lesions were detected using white-light and 32 with ICG. Among the 32 suspected lesions found with ICG, 22 were confirmed to be endometriosis. Seven additional lesions were identified with ICG alone, of which only one was histologically proven endometriosis. Positive predictive values were 89.8%, 68.8% and 86.7% for white-light laparoscopy alone, near-infrared (NIR)-ICG visualization alone, and the combination of white-light and NIR-ICG, respectively. ICG exposure time, previous abdominal surgery and rARSM stage showed a statistically significant impact on the ICG detection rate. In seven patients, ICG was used for the resection of deep infiltrating nodules from the rectum. In these cases, NIR fluorescence imaging with ICG was useful to define the borders between an endometriotic nodule and healthy tissue. CONCLUSIONS: The diagnostic value of NIR-ICG imaging in identifying endometriosis appears to be minimal. ICG exposure time over 20 minutes, no previous abdominal surgery and low rASRM stages have a significant positive effect on the ICG detection rate. NIR fluorescence imaging with ICG was helpful in the resection of deep infiltrating nodules in providing a better visualization of endometriosis.

Early-stage endometrial cancer, CTNNB1 mutations, and the relation between lymphovascular space invasion and recurrence.

INTRODUCTION: Women diagnosed with early-stage (FIGO 1) endometrial cancer, grade 1 and 2 can have a good prognosis. Most of these women can be treated successfully with a hysterectomy and bilateral salpingo-oophorectomy and without the additional adjuvant treatment that is accompanied by more risks for complications. However, when recurrence does occur, the consequences can be dire. Accurate decisions must therefore be made by surgeons to avoid either under- or over-treatment. Risk and patient stratification for tailoring treatment still need further improvement. Both histopathology and genetic variants could be integrated into the decision process if relevant factors were identified. MATERIAL AND METHODS: Morphological features and the presence of selected genetic mutations in isolated malignant endometrial epithelial cells from these tumors were analyzed in a strictly defined cohort of FIGO 1, grade 1 and 2 low-risk endometrial cancer. Their presence in this cohort, their relation to recurrence, and the association between histopathological features and mutations were determined. This analysis was performed using archival formalin-fixed paraffin-embedded tissue, complete re-evaluation of histopathological features, laser capture microdissection of epithelial cells, and a polymerase chain reaction-based mutational screening assay. RESULTS: Twenty-one women with recurrence, after initial identification as low-risk endometrial cancer, were compared with 20 matched control women. The histological marker of lymphovascular invasion was significantly associated with recurrence. There was also a very high prevalence of mutations in CTNNB1 gene, occurring in 50% of this cohort. PTEN mutations were also observed in 27.8% of cases and PIK3CA mutations in 22.2%; none of these mutations were significantly related to recurrence. CONCLUSIONS: This study supports the importance of lymphovascular space invasion to identify women with significant risk for recurrence in initially low-risk, early-stage endometrial cancer. It also identifies CTNNB1 as a significant mutation in early-stage disease, and although it may not represent a marker for recurrence its high prevalence in early stage disease could have relevance for both pathogenesis and early treatment.

Minimally invasive surgery does not impair overall survival in stage IIIC endometrial cancer patients.

PURPOSE: We aimed to evaluate weather survival is impaired in stage IIIC endometrial cancer patients treated with minimally invasive surgery as compared to laparotomy. METHODS: We analyzed surgical data and oncologic outcome of histologically proven stage IIIC endometrial cancer patients who were treated at our institution via laparotomy or via laparoscopic surgery. All the patients underwent a systematic pelvic and para-aortic lymphadenectomy and a complete tumor resection. Perioperative morbidity and overall survival of the patients subjected to the two surgical approaches were compared. RESULTS: Sixty-six patients with stage IIIC endometrial cancer were identified. Of these, 15 patients were operated via laparotomy and 51 via laparoscopy. The two groups were similar with regards to median age at diagnosis, BMI, histotype, number of affected lymph nodes, and median maximal diameter of the affected lymph nodes. Patients undergoing laparoscopic surgery had fewer perioperative complications, a smaller estimated blood loss, and were subjected less frequently to transfusions. Overall survival at 60 months of follow-up did not differ between the two groups. At uni- and multivariate analysis, surgical approach did not affect survival. Only age was a variable associated with overall survival. CONCLUSIONS: Minimally invasive surgery has better perioperative outcomes and does not impair survival in stage IIIC endometrial cancer patients. Age at diagnosis is the only factor independently affecting survival.