Role of sentinel lymph node biopsy with indocyanine green and site of injection in endometrial cancer.

PURPOSE OF REVIEW: The aim of the present narrative review is to summarize the state of art on sentinel lymph node biopsy (SLNB) in endometrial cancer, with a special focus on indocyanine green (ICG) as adopted tracer. RECENT FINDINGS: Over the years, the surgical nodal staging in patients with endometrial cancer has been intensively investigated. Traditionally, systematic pelvic and para-aortic lymphadenectomy represented the gold standard surgical treatment to assess nodal involvement of the tumor. Through the last two decades, SLNB has gradually replaced lymphadenectomy as a more targeted procedure. A great heterogeneity of tracers and injection techniques have been proposed to perform SLNB. However, no universally accepted recommendations are still available. SUMMARY: SLNB has nowadays almost replaced pelvic lymphadenectomy in low-risk endometrial cancers, offering a better safety profile while being related to a comparable nodal involvement sensitivity. Currently, ICG is considered to be the most used tracer among others. Different injection sites have been proposed, with different detection features. While ICG cervical injection is nowadays the suggested technique for SLNB, noncervical injection techniques, such as hysteroscopic and combined procedures, seem to have a better accuracy in para-aortic nodal assessment, which have a role in high-risk endometrial cancers.

Port Site Metastasis in Women with Low- or Intermediate-Risk Endometrial Carcinoma: A Systematic Review of Literature.

Background: Port site metastasis (PSM) has been reported as a rare metastasis in women with endometrial carcinoma (EC). However, even more rarely, it has also been described in patients with low- or intermediate-risk EC. Unfortunately, knowledge appears limited on the topic. Objectives: Our objective was to systematically review the literature on PSM in low- or intermediate-risk EC. Search Strategy: A systematic review of the literature was performed by searching six electronic databases from their inception to January 2023. Selection Criteria: We included in our research all peer-reviewed studies which reported PSM in low- or intermediate-risk EC women. Data Collection and Analysis: Data on PSM were collected from the included studies and compared. Results: Seven studies with 13 patients (including our case) were included in the systematic review. PSM was reported in patients with low- or intermediate-risk EC independently from tumor histologic characteristics, endoscopic approach, lymph node staging type, number and site of the port, route of specimen removal, prevention strategies for PSM, and concomitant metastases. Among several proposed treatments, local resection and radiotherapy with or without chemotherapy might be the most appropriate ones. Nevertheless, the prognosis appears poor. Conclusions: In patients with low- or intermediate-risk EC, PSM can occur as a rare metastasis, regardless of tumor characteristics or surgical strategy. Unfortunately, no consensus has been reached regarding treatment, and the prognosis appears poor. Additional cases are needed in order to confirm and further explore this rare EC metastasis.

Painful sexual intercourse, quality of life and sexual function in patients with endometriosis: not just deep dyspareunia.

PURPOSE: To evaluate the prevalence of deep and superficial dyspareunia in women with diagnosis of endometriosis. Secondly, to assess the temporal relation between deep and superficial dyspareunia in women reporting both symptoms (concomitant dyspareunia) and the impact on quality of life (QoL) and sexual function. METHODS: This is a cross-sectional cohort study that included fertile women with diagnosis of endometriosis. Enrolled subjects reported pain symptoms including dyspareunia and its temporal onset and completed two one-time validated questionnaires regarding sexual function (Female Sexual Function Index) and QoL (International QoL Assessment SF-36). RESULTS: Among the 334 enrolled patients, 75.7% (95%) reported dyspareunia. Women were divided into four groups according to the presence and type of dyspareunia: isolated superficial dyspareunia (6.3%), isolated deep dyspareunia (26.0%), concomitant dyspareunia (43.4%) and no dyspareunia (24.3%). Women with concomitant dyspareunia reported higher NRS scores than women with isolated dyspareunia or no dyspareunia (P ≤ 0.001). The majority of women with concomitant dyspareunia (56.6%) reported that deep dyspareunia developed before superficial dyspareunia. Women with concomitant dyspareunia reported worse QoL and worse sexual function than women with isolated dyspareunia or without dyspareunia (P ≤ 0.001). CONCLUSION: Dyspareunia is a common symptom in women with endometriosis, with many reporting concomitant deep and superficial dyspareunia. Concomitant dyspareunia can significantly impact sexual function and quality of life (QoL). Therefore, it is crucial to investigate dyspareunia thoroughly and differentiate between its types to tailor effective therapeutic strategies.

Primary omental pregnancy after in vitro fertilization complicated by hemoperitoneum-how to manage it laparoscopically.

OBJECTIVE: To report an uncommon case of primary OP treated laparoscopically. Ectopic pregnancy (EP) is the leading cause of maternal mortality during the first trimester and the incidence increases with assisted reproductive techniques, occurring in approximately 1.5%-2.1% of patients undergoing in vitro fertilization.1 Omental pregnancy (OP) is an extremely rare form of EP accounting for less than 1% of all EPs. OP can be classified as primary or secondary on the basis of Studdiford's criteria2. The preoperative diagnosis of OP is complex and usually occur in acute circumstances during a throughout intraoperative evaluation of the abdomen.3-5 A delayed diagnosis poses a serious threat to the survival of the patient; therefore, it is important to remark that EP can exist in unusual locations and prompt surgical intervention may be necessary. DESIGN: A step-by-step narrated video of a rare clinical case and description of the surgical procedure. SETTING: Tertiary Level Academic Hospital "IRCCS Azienda Ospedaliero - Universitaria di Bologna" Bologna, Italy. PATIENT: A 36-year-old woman was referred to our emergency room because of acute abdominal pain and nausea for 2 hours with no signs of hemodynamic instability. The patient also complained that poor vaginal bleeding appeared during the last 24 hours. The patient has undergone a cycle of in vitro fertilization with an elective single frozen embryo transfer of a blastocyst on day 5, 2 months before. She had no relevant clinical or surgical history. Diffuse abdominal tenderness and a painful uterus at mobilization were appreciated at clinical examination. A massive hemoperitoneum was diagnosed using transvaginal-transabdominal ultrasound, and no uterine or adnexal lesions were identified. The ß-human chronic gonadotropin level was 43.861 mIU/mL, and the hemoglobin value was 10.5 g/dL. INTERVENTIONS: On suspicion of a ruptured EP, after detailed counseling and the acquisition of informed consent, a laparoscopic exploration was planned. First, the hemoperitoneum was evacuated to allow visualization of the abdominal cavity. At pelvic inspection, no EP was found. Throughout the exploration of the abdominal cavity, a 4-cm bluish cystic mass of friable consistency was detected infiltrating the omentum and the mesentery. According to Studdiford's criteria, the diagnosis of a primary OP was established. A careful and complete excision of the ectopic implant was performed with an ultrasonic system and required a considerable hemostatic effort using bipolar energy, endoscopic clips, and mechanical compression. The postoperative course was uneventful. The ß-human chronic gonadotropin levels gradually decreased to negative values within 29 days after surgery. MAIN OUTCOME MEASURE(S): Omental ectopic pregnancy can be successfully managed with a laparoscopic approach even in an emergency setting. CONCLUSION: Omental pregnancy can easily be overlooked, even by skilled surgeons, during laparoscopic exploration. It is mandatory that all peritoneal surfaces and the omentum be carefully inspected during surgery in patients without other signs of pelvic EP.We confirm that the patient included in this video gave consent for publication of the video and posting of the video online, including on social media, the journal website, scientific literature websites, and other applicable sites.

Progression of adenomyosis: Rate and associated factors.

OBJECTIVE: To evaluate the rate of disease progression and the factors associated with such progression in patients with an ultrasound diagnosis of adenomyosis. METHODS: This was a single center, prospective, observational, cohort study performed at a tertiary referral center. Patients who obtained an ultrasound diagnosis of adenomyosis from May 2022 to August 2022 were recruited. Demographic, clinical and ultrasound data were recorded at the first visit (T0) and after 12 months (T1) for enrolled patients and compared between T0 and T1. The study population was divided in two groups according to progression (increase in uterine volume >20%) or stability/regression (decrease or increase in uterine volume ≤20%) of adenomyosis at T1. Primary study outcome was the rate of adenomyosis progression, while secondary study outcome was the association of adenomyosis progression with demographic and clinical factors. Post hoc subgroups analyses for primary and secondary study outcomes were performed based on hormonal therapy (untreated and treated). RESULTS: A total of 221 patients were enrolled in the study, with no significant difference in terms of baseline data among the two study groups and no patients were lost to follow-up. The overall rate of adenomyosis progression was 21.3% (47/221 patients). The rate was 30.77% in hormonally untreated women, and 18.34% in hormonally treated women. Progression was associated with the presence of focal adenomyosis of the outer myometrium (P = 0.037), moderate to severe dysmenorrhea (P = 0.001), chronic pelvic pain (P = 0.05), dyschezia (P = 0.05), and worsening of chronic pelvic pain (P = 0.04) at T1. CONCLUSION: Adenomyosis showed a rate of disease progression of 21.3% at the 12-month follow-up (30.77% in hormonally untreated women, and 18.34% in hormonally treated women). The presence and/or worsening of painful symptoms, such as severe dysmenorrhea, dyschezia and chronic pelvic pain, as well as the presence focal adenomyosis of the outer myometrium, might help identify patients at higher risk of disease progression and tailor their follow-up.

Robotic assisted versus laparoscopic surgery for deep endometriosis: a meta-analysis of current evidence.

Endometriosis is a benign inflammatory onco-mimetic disease affecting 10-15% of women in the world. When it is refractory to medical treatments, surgery may be required. Usually, laparoscopy is the preferred approach, but robotic surgery has gained popularity in the last 15 years. This study aims to evaluate the safety and efficacy of robotic-assisted laparoscopic surgery (RAS) versus conventional laparoscopic surgery (LPS) in the treatment of endometriosis. This study adheres to PRISMA guidelines and is registered with PROSPERO. Studies reporting perioperative data comparing RAS and LPS surgery in patients with endometriosis querying PubMed, Google Scholar and ClinicalTrials.gov were included in the analysis. The Quality Assessment of Diagnostic Accuracy Studies 2 tool (QUADAS-2) was used for the quality assessment of the selected articles. Fourteen studies were identified, including 2709 patients with endometriosis stage I-IV for the meta-analysis. There were no significant differences between RAS and LPS in terms of intraoperative and postoperative complications, conversion rate and estimated blood loss. However, patients in the RAS group have a longer operative time (p < 0.0001) and longer hospital stay (p = 0.020) than those in the laparoscopic group. Robotic surgery is not inferior to laparoscopy in patients with endometriosis in terms of surgical outcomes; however, RAS requires longer operative times and longer hospital stay. The benefits of robotic surgery should be sought in the easiest potential integration of robotic platforms with new technologies. Prospective studies comparing laparoscopy to the new robotic systems are desirable for greater robustness of scientific evidence.

Feasibility of Intraoperative Proctosigmoidoscopy After Discoid Bowel Resection for Deep Infiltrating Endometriosis: A Pilot Multicenter Study.

STUDY OBJECTIVE: Although surgery is the gold standard treatment for pain refractory to medical management or partial occlusion owing to rectosigmoid endometriosis, surgical resection can be associated with major perioperative complications. From general surgery experience, intraoperative proctosigmoidoscopy has shown encouraging results as a feasible, safe, and effective technique in reducing the risk of complications related to intestinal anastomosis after segmental resection. Unfortunately, there are no studies evaluating its role after discoid resection for rectosigmoid endometriosis. DESIGN: A pilot, multicentric, observational, prospective, cohort study. SETTING: Two academic hospitals, from March 1 to December 31, 2022. PATIENTS: We enrolled all consecutive fertile-age patients affected by symptomatic endometriosis scheduled for laparoscopic discoid bowel resection. Inclusion criteria were (1) age between 18 and 50 years, (2) diagnosis of rectosigmoid endometriosis performed by transvaginal ultrasound and/or magnetic resonance imaging, and (3) women scheduled for laparoscopic discoid bowel resection of endometriosis at low risk of segmental resection. INTERVENTIONS: During data analysis, enrolled patients were divided into 2 study groups for comparisons based on whether or not the intraoperative proctosigmoidoscopy was performed upon surgeons' discretion after discoid resection for treating endometriosis, in addition to standard integrity tests. Primary outcome was the rate of intraoperative proctosigmoidoscopy success. Secondary study outcomes were the differences between the intraoperative proctosigmoidoscopy group and the nonintraoperative proctosigmoidoscopy group in (1) mean of total operative time and (2) rate of perioperative complications. MEASUREMENTS AND MAIN RESULTS: A total of 28 patients were enrolled and equally distributed in the 2 groups. The rate of intraoperative proctosigmoidoscopy success was 86%. No significant difference was reported between the 2 groups in terms of total operative time (p = .1) and intraoperative and postoperative complications (p = .5 and p = 1, respectively), with no surgical complication related to intraoperative proctosigmoidoscopy. CONCLUSION: Intraoperative proctosigmoidoscopy seems as a feasible and non-time-consuming intraoperative procedure in women undergone discoid resection for rectosigmoid endometriosis. Larger studies with longer follow-up period are necessary to confirm our findings and assess clinical benefits over standard procedure.

Integrated histological parameters define prognostically relevant groups in atypical endometrial hyperplasia/endometrioid intraepithelial neoplasia.

OBJECTIVE: To assess the risk of endometrial carcinoma following a diagnosis of atypical hyperplasia/endometrioid intraepithelial neoplasia by endometrial biopsy, stratified based on integrated histological parameters. METHODS: All women with atypical hyperplasia/endometrioid intraepithelial neoplasia undergoing hysterectomy within 1 year of diagnosis without progestin treatment were included. Patients were subdivided into three study groups, based on two criteria: (a) grade of nuclear atypia and (b) foci (<2 mm) of confluent glands with no intervening stroma: low-grade, high-grade, and confluent glands. The rate of endometrial carcinoma on the subsequent hysterectomy was assessed in each study group, and differences between study groups were assessed using Fisher's exact test, with a significant p value <0.05. Reproducibility was assessed by using Cohen's κ. RESULTS: Ninety-six patients were included. Overall, 36 of 96 patients (37.5%) had endometrial carcinoma on the subsequent hysterectomy. The number of endometrial carcinomas was 4 of 42 (9.5%) in the low-grade group, 14 of 28 (50.0%) in the high-grade group, and 18 of 26 (69.2%) in the confluent glands group. The rate of endometrial carcinoma was significantly higher in the high-grade group than in the low-grade group (p<0.001), whereas it did not significantly differ between the high-grade group and the confluent glands group (p=0.176). The reproducibility among pathologists was moderate for low-grade versus high-grade (κ=0.58) and substantial for confluent glands versus low-grade (κ=0.63) and high-grade (κ=0.63). CONCLUSION: Atypical hyperplasia/endometrioid intraepithelial neoplasia can be stratified into prognostically relevant groups based on integrated histological parameters, with a possible major impact on patient management.

Endometriosis-Related Ovarian Cancer: Where Are We Now? A Narrative Review towards a Pragmatic Approach.

BACKGROUND: Endometriosis affects more than 10% of reproductive-aged women, causing pelvic pain and infertility. Despite the benign nature of endometriosis, ovarian endometriomas carry a higher risk of developing endometrioid carcinomas (EnOCs) and clear cell ovarian carcinomas (CCCs). Atypical endometriosis, defined as cytological atypia resembling intraepithelial cancer, is considered the precursor of endometriosis-associated ovarian cancer (EAOC). This narrative review aims to provide an overview of EAOC, proposing a practical approach to clinical and therapeutic decision making. METHODS: An electronic literature search was conducted from inception up to January 2023, using the MEDLINE database via PubMed to evaluate the existing literature on EAOC, including its pathogenesis, the diagnostic process, and the therapeutic possibilities, with articles not relevant to the topic or lacking scientific merit being excluded. RESULTS: Eighty-one articles were included in the review to present the current state of the art regarding EAOC. A pragmatic clinical flowchart is proposed to guide therapeutic decisions and improve patient outcomes. CONCLUSIONS: Endometriosis patients may have an increased risk of developing EAOC (either EnOC or CCC). Despite not being fully accepted, the concept of AE may reshape the endometriosis-ovarian cancer relationship. Further research is needed to understand the unaddressed issues.

"Robot-Assisted Partial Cystectomy for Deep Infiltrating Endometriosis of the Bladder With the Hugo RAS System".

OBJECTIVE: Involvement of the lower urinary tract is found in 0.2 to 2.5% of all deep infiltrating endometriosis (DIE) [1,2]. The bladder is the most affected organ with a prevalence of up to 80% of cases [3]. Patients with bladder endometriosis are often symptomatic (dysuria, hyperactive bladder, recurrent urinary tract infections, and hematuria). Surgery is the gold standard treatment for this condition when medical therapy fails [1,2]. Several studies have shown the feasibility, effectiveness, and safety of the laparoscopic approach [4] but data about robotic-assisted approach are missing in literature. Currently, novel platforms are entering the market and the Hugo™RAS (Medtronic, Minneapolis, USA) is a new system (HRS) consisting of an open console with 3D-HD screen and a multimodular bedside units. Even if some series are already available for radical cystectomies for oncologic purposes [5], a full description of DIE surgery performed with HRS is still lacking. Aim of this video-article is to show our technique and surgical setup to carry out a complex case of anterior compartment DIE. DESIGN: A step-by-step explanation of surgical technique with narrated video footage. SETTING: Tertiary Level Academic Hospital "IRCCS Azienda Ospedaliero-Universitaria di Bologna" Bologna, Italy. INTERVENTION: A 36-year-old nulliparous woman affected by DE was referred to our center due to severe dyspareunia, dysuria with hematuria and postvoiding pain not responsive to oral progestins. The preoperative work up consisted of a gynecological examination, pelvic ultrasound and MRI that showed the presence of an endometriotic nodule of the bladder base. All possible therapeutic strategies and related complications have been discussed with the patient before the signature of the informed consent. To carry out the procedure a "straight" port placement in a "compact" docking configuration [6] was installed. After developing the paravesical spaces bilaterally, the bladder nodule was approached in a latero-medial direction then a partial cystectomy with macroscopical free margins was performed. A double layer horizontal running suture with barbed thread was used to repair the bladder wall. CONCLUSION: To the best of our knowledge, this is the first case of bladder endometriotic nodule excision performed with HRS. We explained our technique and robotic set-up to successfully manage a compelx case of DIE of the bladder.

Ovarian tissue biopsy for cryopreservation by vaginal natural orifice transluminal endoscopic surgery: a new approach for a minimal invasive ovarian biopsy.

OBJECTIVE: Vaginal natural orifice transluminal endoscopic surgery (vNOTES) is an emerging surgical procedure that combines the advantages of the vaginal approach with laparoscopic vision and instrumentation. Shorter hospitalization and lesser postoperative pain associated with vNOTES may be explained by the advantages of this innovative surgical approach (e.g., absence of abdominal incisions, shorter operative time, and lower insufflation pressure). Ovarian tissue cryopreservation allows to preserve reproductive and endocrine functions in young women with oncological disease at risk of premature ovarian insufficiency (POI) caused by gonadotoxic treatments. Ovarian tissue biopsy for cryopreservation consists of a large biopsy of 1 or both ovaries that is usually performed by laparoscopy. Then, the removed ovarian tissue is cryopreserved for the future transplant after cancer remission. The volume of ovarian biopsy ranges from 50% of the ovary for women at moderate risk of POI to 70%-100% of it for those at high risk. The inclusion criteria for ovarian tissue cryopreservation are women aged <35 years who cannot delay start of oncological treatments for follicle cryopreservation, with a moderate or high risk of POI and good chance of 5-year survival. Ovarian tissue cryopreservation cannot be performed if tumor treatments include uterine irradiation or for tumors at risk of ovarian metastases (as in the case of ovarian cancer, leukemia, neuroblastoma, or Burkitt lymphoma). Despite widespread adoption of vNOTES in gynecology, ovarian biopsy for cryopreservation has never been performed using this route. DESIGN: Step-by-step explanation of the procedure with descriptive text and narrated video footage. SETTING: Tertiary-level referral academic center. PATIENT(S): A 27-year-old patient recently diagnosed with low-grade follicular non-Hodgkin lymphoma was referred to our center for ovarian tissue cryopreservation before chemotherapy. The patient included in this study gave informed consent for publication of the video and posting of the video online including social media, the journal website, scientific literature websites (e.g., PubMed, ScienceDirect, and Scopus), and other applicable sites. Because of the nature of the study, institutional review board approval was not required. INTERVENTION(S): Access to the peritoneal cavity was created by a 3-cm posterior colpotomy. The peritoneum was then opened using cold scissors and temporarily fixed to the posterior vaginal wall. The GelPOINT Mini Advanced Access Platform (Applied Medical, Rancho Santa Margarita, CA), with 1 10-mm and 2 5-mm trocars, was used as the vNOTES port. The inner Alexis ring of the GelPOINT was inserted through the colpotomy into the pouch of Douglas. A hysterometer was placed into the uterine cavity to keep the uterus anteverted during the surgery. A pneumoperitoneum was created to a pressure of 8 mm Hg, and the operating table was tilted to a 20° Trendelenburg position. A 10-mm rigid 30° camera was inserted in the inferior and larger trocar, and both ovaries were visualized. Seventy percent of the left ovary was removed with cold scissors to minimize trauma on the surgical specimen. After removal of the GelPOINT cap, ovarian biopsy was immediately picked up by the biologist of our fertility center. The ovary was coagulated with a bipolar instrument. The hysterometer was then replaced by a uterine manipulator to perform tubal patency test, and blue dye passage through both salpinges was observed. Finally, the Alexis retractor and stich on the posterior peritoneum were removed, and the vagina was sutured using interrupted stiches. The total operative time was 25 minutes. MAIN OUTCOMES MEASURE(S): Ovarian tissue biopsy for cryopreservation by vNOTES. RESULT(S): No intraoperative and postoperative complications were reported, and the patient was discharged after 24 hours from surgery. CONCLUSION(S): Vaginal natural orifice transluminal endoscopic surgery may be a feasible alternative approach to laparoscopy for ovarian tissue cryopreservation: it allows an easy access to the ovaries and removal of different tissue volumes. Patients undergoing ovarian cryopreservation may benefit from the vNOTES approach because a rapid postoperative recovery is crucial to start chemotherapy in a short time. As for other vNOTES procedures, accurate selection of patients seems to be crucial for a successful ovarian tissue cryopreservation. We believe that the inclusion and exclusion criteria reported for other gynecologic procedures performed through vNOTES may also be valid for ovarian tissue cryopreservation by vNOTES. Women at high risk of pelvic adhesions (e.g., coexistent endometriosis, previous pelvic surgery, or inflammatory pelvic disease), those with an increased body mass index or enlarged uterus, and those with cervical, vaginal, or uterine cancer cannot be considered for this approach because all these factors are associated with failure of vNOTES. On the other hand, women with no history of surgery, endometriosis, and large myomas may benefit from the vNOTES approach, and these women represent most of patients who undergo ovarian tissue cryopreservation. Further and larger studies are needed to assess the efficacy and safety of this new approach.

Detection and Classification of Hysteroscopic Images Using Deep Learning.

BACKGROUND: Although hysteroscopy with endometrial biopsy is the gold standard in the diagnosis of endometrial pathology, the gynecologist experience is crucial for a correct diagnosis. Deep learning (DL), as an artificial intelligence method, might help to overcome this limitation. Unfortunately, only preliminary findings are available, with the absence of studies evaluating the performance of DL models in identifying intrauterine lesions and the possible aid related to the inclusion of clinical factors in the model. AIM: To develop a DL model as an automated tool for detecting and classifying endometrial pathologies from hysteroscopic images. METHODS: A monocentric observational retrospective cohort study was performed by reviewing clinical records, electronic databases, and stored videos of hysteroscopies from consecutive patients with pathologically confirmed intrauterine lesions at our Center from January 2021 to May 2021. Retrieved hysteroscopic images were used to build a DL model for the classification and identification of intracavitary uterine lesions with or without the aid of clinical factors. Study outcomes were DL model diagnostic metrics in the classification and identification of intracavitary uterine lesions with and without the aid of clinical factors. RESULTS: We reviewed 1500 images from 266 patients: 186 patients had benign focal lesions, 25 benign diffuse lesions, and 55 preneoplastic/neoplastic lesions. For both the classification and identification tasks, the best performance was achieved with the aid of clinical factors, with an overall precision of 80.11%, recall of 80.11%, specificity of 90.06%, F1 score of 80.11%, and accuracy of 86.74 for the classification task, and overall detection of 85.82%, precision of 93.12%, recall of 91.63%, and an F1 score of 92.37% for the identification task. CONCLUSION: Our DL model achieved a low diagnostic performance in the detection and classification of intracavitary uterine lesions from hysteroscopic images. Although the best diagnostic performance was obtained with the aid of clinical data, such an improvement was slight.

Where Morphological and Molecular Classifications Meet: The Role of p53 Immunohistochemistry in the Prognosis of Low-Risk Endometrial Carcinoma (GLAMOUR Study).

No prospective study has validated molecular classification to guide adjuvant treatment in endometrial cancer (EC), and not even retrospective data are present for patients with morphological low-risk EC. We conducted a retrospective, multicenter, observational study including 370 patients with low-risk endometrioid EC to evaluate the incidence and prognostic role of p53 abnormal expression (p53abn) in this specific subgroup. Among 370 patients, 18 had abnormal expressions of p53 (4.9%). In 13 out of 370 patients (3.6%), recurrences were observed and two were p53abn. When adjusting for median follow-up time, the odds ratio (OR) for recurrence among those with p53abn versus p53 wild type (p53wt) was 5.23-CI 95% 0.98-27.95, p = 0.053. The most common site of recurrence was the vaginal cuff (46.2%). One recurrence occurred within the first year of follow-up, and the patient exhibited p53abn. Both 1-year and 2-year DFS rates were 94.4% and 100% in the p53abn and p53wt groups, respectively. One patient died from the disease and comprised p53wt. No difference in OS was registered between the two groups; the median OS was 21.9 months (16.4-30.1). Larger multicenter studies are needed to tailor the treatment of low-risk EC patients with p53abn. Performing molecular classification on all EC patients might be cost-effective, and despite the limits of our relatively small sample, p53abn patients seem to be at greater risk of recurrence, especially locally and after two years since diagnosis.

Ovarian tissue transplantation: 10 years of experience at the Bologna University.

Objective: The efficiency of ovarian tissue transplantation (OTT) was established in terms of ovarian function recovery (95% of cases), number of live births (over 200 worldwide to date) and induction of puberty. Unfortunately, the lack of international registries and the fact that many centers have not yet reported their outcomes, lead to poor knowledge of the exact fertility data. The aim of the study is to describe our experience with OTT to restore ovarian function and fertility. Methods: This study was designed as a single-center, observational, retrospective, cohort study that includes women who underwent OTT between December 2012 and June 2023 at our center. After approval by the oncologist/hematologist, a small fragment of ovarian tissue was thawed and analyzed to detect the presence of micrometastases before OTT. Thawed ovarian tissue was grafted laparoscopically at multiple sites, including the remaining ovary and pelvic side wall (orthotopic transplantation) and/or abdominal wall (heterotopic transplantation). After OTT, ovarian function was monitored by hormonal assay, ultrasound and color Doppler at approximately 4-week intervals. Results: Between December 2012 and June 2023, 30 women performed OTT. Prior to OTT, immunohistochemical and molecular analyses revealed no micrometastases in all thawed ovarian tissue samples. In our series of 30 women, 20 of women were on premature ovarian insufficiency (POI), and the remaining ten cases still had oligomenorrhea and difficulty getting pregnant. Among the women with POI before OTT and at least 6 months follow-up, recovery of endocrine function was observed in all but one woman who underwent orthotopic transplantation (13 of 14 cases), in one out of two women who underwent both orthotopic and heterotopic transplantation (1 of 2 cases) and in all women who underwent heterotopic transplantation (4 of 4 cases). Women who underwent OTT to enhance fertility had no alterations in menstrual cycle and hormonal levels. In total, ten pregnancies were obtained in 25 women, resulting in four live births, two ongoing pregnancies and four spontaneous abortions. Conclusion: Our data can help patients and physicians in their discussions and decisions about the need and possibilities of preserving fertility.

Adenomyosis among patients undergoing postpartum hysterectomy for uncontrollable uterine bleeding: A multicenter, observational, retrospective, cohort study on histologically-based prevalence and clinical characteristics.

OBJECTIVE: To assess the prevalence of adenomyosis at pathologic examination, and its association with obstetric complications, peripartum maternal clinical characteristics and neonatal birth weight in patients undergoing postpartum hysterectomy due to postpartum hemorrhage (PPH). METHODS: A multicenter, observational, retrospective, cohort study was carried out including all women who underwent postpartum hysterectomy due to PPH at gestational week 23+0 or later, between January 2010 and May 2023. Patients were categorized into two groups based on the presence of adenomyosis at pathologic examination, and were compared for obstetric complications, peripartum maternal clinical characteristics, and neonatal birth weight. RESULTS: The histologically-based prevalence of adenomyosis in patients undergoing postpartum hysterectomy due to PPH was 39.4%. Adenomyosis was associated with a longer hospitalization time (regression coefficient: 4.43 days, 95% CI: 0.34-8.52, P = 0.034) and a higher risk of hypertensive disorders (OR: 5.82, 95% CI: 1.38-24.46, P = 0.016), threatened preterm labor (OR: 3.34, 95% CI: 1.08-10.31, P = 0.036), urgent/emergency C-section (OR: 24.15, 95% CI: 2.60-223.96, P = 0.005), postpartum maternal complications (OR: 4.96, 95% CI: 1.48-16.67, P = 0.012), maternal intensive care unit admission (OR: 3.56, 95% CI: 1.05-12.05, P = 0.041), and low birth weight neonates (OR: 3.8, 95% CI: 1.32-11.02, P = 0.013). CONCLUSION: In patients undergoing postpartum hysterectomy due to PPH, adenomyosis is a highly prevalent condition among, and is associated with adverse obstetric, maternal, and neonatal outcomes.

Laparoscopic medulla-sparing ovarian tissue biopsy for cryopreservation: step-by-step surgical technique.

OBJECTIVE: To describe a laparoscopic technique for ovarian tissue biopsy (OTB) for fertility preservation. In the last years, the demand for fertility preservation has grown because of the increasing survival rates among patients with cancer and the rising awareness of the importance of quality of life after gonadotoxic therapy. Among fertility-sparing approaches, ovarian tissue cryopreservation is a valid strategy to preserve ovarian endocrine and reproductive function in prepubertal and postpubertal women who will undergo gonadotoxic cancer treatments. Currently, there is no universal consensus regarding ovarian tissue retrieval technique for fertility preservation. DESIGN: Step-by-step description of the surgical technique with narrated video footage. SETTING: Academic tertiary hospital. PATIENT(S): Patients with a high risk of premature ovarian insufficiency, usually due to gonadotoxic treatments, who undergo OTB for fertility preservation were included in the study. In this video, we present the clinical case of a 28-year-old patient affected by Hodgkin lymphoma who underwent laparoscopy for OTB before chemotherapy. INTERVENTION(S): After exposing the chosen ovary, an incision at the tubal pole of the ovary is made with scissors. Through section and dissection, a large cortical biopsy of the ovary is performed without removing and avoiding any damage to the medulla. At the end of the procedure, hemostasis was achieved with selective coagulation using bipolar coagulation. MAIN OUTCOME MEASURE(S): Step by step educational video. RESULT(S): The post-operative course was uneventful and the patient was discharge 24 hours after surgery. CONCLUSION(S): Standardization of a step-by-step laparoscopic technique can provide an effective method to optimize ovarian tissue removal while minimizing tissue injury. Medulla-sparing ovarian biopsy allows retrieval of only the cortical part of the ovary, maximizing the number of primordial follicles obtained without damaging the vascular supply of the ovary contained within the medulla. Primordial follicles are resistant to cryoinjury owing to their relatively inactive metabolism, and they are usually found at approximately 0.8 mm below the surface of the cortex. This technique could also reduce the back-table processing time of the ovarian tissue before cryopreservation. One disadvantage could be the difficulty of the technique compared to an oophorectomy because it requires a skilled surgeon that can easily find the cleavage plane between the medulla and the cortex, even in patients submitted to previous chemoradiotherapy or during gonadotropin-releasing hormone analogue therapy.

Assessment of sentinel Lymph node mapping with different volumes of Indocyanine green in early-stage ENdometrial cancer: the ALIEN study.

OBJECTIVE: To evaluate the impact of different volumes of indocyanine green (ICG) on the detection rate and bilateral mapping of sentinel lymph nodes in patients with apparent uterine-confined endometrial cancer. METHODS: All patients who underwent surgical staging with sentinel node mapping in six reference centers were included. Two different protocols of ICG intracervical injection were used: (1) 2 mL group: total volume of 2 mL injected superficially; (2) 4 mL group: total volume of 4 mL, 2 mL deeply and 2 mL superficially. Logistic regression was used to analyze factors that could influence dye migration and detection rates. A sensitivity analysis was carried out to determine how independent variables could affect the sentinel node detection rate. RESULTS: Of 442 eligible patients, 352 were analyzed (172 in the 2 mL group and 180 in the 4 mL group). The bilateral detection rates of the 2 mL and 4 mL groups were 84.9% and 86.1%, respectively (p=0.76). The overall detection rate was higher with a volume of 4 mL than with 2 mL (97.8% vs 92.4%, respectively; p=0.024). In the univariate analysis the rate of bilateral mapping fell from 87.5% to 73.5% when the International Federation of Gynecology and Obstetrics (FIGO) 2009 tumor stage was >IB (p=0.018). In the multivariate analysis, for both overall and bilateral detection rates a statistically significant difference emerged for the volume of ICG injected and FIGO 2009 stage >IB. Increasing body mass index was associated with worse overall detection rates on univariate analysis (p=0.0006), and significantly decreased from 97% to 91% when the body mass index exceeded 30 kg/m2 (p=0.05). CONCLUSIONS: In patients with early-stage endometrial cancer, a volume of 2 mL ICG does not seem to compromise the bilateral detection of sentinel lymph nodes. In women with obesity and FIGO 2009 stage >IB, a 4 mL injection should be preferred.

Does Sexual Function and Quality of Life Improve after Medical Therapy in Women with Endometriosis? A Single-Institution Retrospective Analysis.

BACKGROUND: Endometriosis is a gynecological condition affecting up to 10% of women of reproductive age and characterized by chronic pain. Pain is the major cause of the impairment of quality of life in all aspects of these patients. Previous studies have shown that endometriosis treatment, hormonal or surgical, has proven effective not only in controlling the disease but also in improving symptoms, and we can assume also effective in improving quality of life. METHODS: This study evaluates quality of life and sexual function in patients with endometriosis at the time of diagnosis and after 6 months of medical therapy, to assess the impact of treatment on these aspects. We evaluated retrospectively patients with a diagnosis of endometriosis between 2018 and 2020. All patients underwent gynecological examination and transvaginal ultrasound and filled in three questionnaires. The same evaluation was provided after taking medical hormonal therapy. RESULTS: The improvement of dysmenorrhea, chronic pelvic pain, and dyspareunia after medical treatment were statistically significant. Instead, items concerning arousal, lubrication, and sexual satisfaction showed a statistically significant worsening after therapy. CONCLUSIONS: We can state that hormone therapy alone is not sufficient to achieve an improvement in the patient's quality of life and sexual function. Emerging evidence suggests that most of these patients showed a central sensibilization phenomenon characterized by an amplification of the response to a peripheral and/or neuropathic nociceptive trigger, which is expressed by hyperalgesia and allodynia. For this reason, in these patients, it is better to adopt a multimodal and multidisciplinary approach, including other professional figures, that acts on pain and also intervenes in all those conditions that contribute to worsening quality of life.

Effects of Pelvic Floor Muscle Physiotherapy on Urinary, Bowel, and Sexual Functions in Women with Deep Infiltrating Endometriosis: A Randomized Controlled Trial.

Background and Objectives: Endometriosis is a chronic and recurrent disease defined as the presence and proliferation of endometrial glands and stroma outside the uterine cavity. It affects up to 6-10% of women of reproductive age and can be classified into superficial, ovarian, and deep infiltrating endometriosis (DIE). Deep infiltrating endometriosis can be associated with pain symptoms and pelvic floor muscle hypertone. Moreover, it may be responsible of bowel, urinary, and sexual dysfunctions with impairment of women's quality of life. Few studies have investigated the role of physiotherapy in women with DIE. Here, we aimed first to evaluate the effects of pelvic floor physiotherapy (PFP) on urinary, bowel, and sexual functions. Secondly, we aimed to evaluate the effects of ultrasound visual feedback during PFP on pelvic floor and subjective modifications in the frequency of sexual intercourse. Materials and Methods: This randomized controlled trial was conducted between June 2018 and December 2019 at our tertiary center. Nulliparous women with DIE and superficial dyspareunia were enrolled. At first examination, levator hiatal area (LHA) assessed with 3D/4D transperineal ultrasound, pain symptoms, urinary, bowel, and sexual functions were evaluated. Then, women were randomly assigned to no intervention (control group) or treatment with five individual sessions of PFP (experimental group), and after four months women underwent a second examination. Urinary, bowel, and sexual functions were assessed with validated questionnaires at first and second examinations. In particular, the Bristol Female Lower Urinary Tract Symptoms questionnaire was used to evaluate urinary symptoms, the Knowles-Eccersley-Scott-Symptom questionnaire to assess the presence of constipation, and the Female Sexual Function Index to investigate sexual function. Study outcomes were the comparisons among groups in terms of differences in actual changes in median of questionnaire scores between first and second examinations. Results: Thirty women (17 in the experimental group and 13 in the control group) completed the study. No significant differences were found between the two groups regarding urinary, bowel, and sexual functions, although women in the experimental group showed a tendency towards an improvement in constipation symptoms. Conclusion: In women with DIE, PFP does not appear to affect urinary, bowel, and sexual functions. Therefore, despite the improvement in superficial dyspareunia, chronic pelvic pain, and PFM relaxation with high treatment satisfaction, women should be informed about the unclear impact of PFP on urinary, bowel, and sexual functions. Larger studies are necessary to further investigate the impact of PFP on these functions.