Clinical outcomes in women with endometrial polyps underwent conservative management.

OBJECTIVE: To evaluate the regression rate of endometrial polyps (EPs) in a cohort of asymmetric women after conservative follow-up. MATERIALS AND METHODS: In this retrospective cohort study, a total of 1006 women with asymptomatic EPs were treated with expectant management or hormonal drugs between June 1999 and May 2018. Four hundred forty-eight women (44.5%) were administered with hormonal medications and 558 women were managed expectantly (55.5%). Office hysteroscopy was performed to confirm the diagnosis and regression of EPs. Hormonal administration included oral contraceptives, progestin and cyclic estrogen/progestin regimen according to physicians' preferences. Clinical characteristics, including the patient's age, body mass index, parity, and type of conservative management were collected. RESULTS: The mean observation time was 14.1 ± 18.5 months (range, 1-162 months). The overall regression rate of EPs in this cohort was 33.5%, 24.6% occurred after medication and 8.9% after expectant management. Patient age (<50 years) (p < 0.001), follow-up period (p = 0.005) and hormonal drugs used (p < 0.001) were significantly associated with EP regression. Twenty-four (7.1%) of the 337 EP regression patients later developed recurrent disease. Follow-up period (p < 0.001) and hormonal drugs used (p = 0.032) were closely related to polyp recurrence after initial regression. Nevertheless, multivariate logistic regression analysis revealed that hormonal drugs used was significantly associated with the regression (p < 0.001) and recurrence (p = 0.016) of EPs. CONCLUSION: Women aged 50 or less are more suitable for conservative treatment for EPs. Hormonal drugs used could increase the incidence of EP regression.

Analysis of endometrial lavage microbiota reveals an increased relative abundance of the plastic-degrading bacteria Bacillus pseudofirmus and Stenotrophomonas rhizophila in women with endometrial cancer/endometrial hyperplasia.

The pathogenic influences of uterine bacteria on endometrial carcinogenesis remain unclear. The aim of this pilot study was to compare the microbiota composition of endometrial lavage samples obtained from women with either endometrial hyperplasia (EH) or endometrial cancer (EC) versus those with benign uterine conditions. We hypothesized that specific microbiota signatures would distinguish between the two groups, possibly leading to the identification of bacterial species associated with endometrial tumorigenesis. A total of 35 endometrial lavage specimens (EH, n = 18; EC, n = 7; metastatic EC, n = 2; benign endometrial lesions, n = 8) were collected from 32 women who had undergone office hysteroscopy. Microbiota composition was determined by sequencing the V3-V4 region of 16S rRNA genes and results were validated by real-time qPCR in 46 patients with EC/EH and 13 control women. Surprisingly, we found that Bacillus pseudofirmus and Stenotrophomonas rhizophila - two plastic-degrading bacterial species - were over-represented in endometrial lavage specimens collected from patients with EC/EH. Using computational analysis, we found that the functional profile of endometrial microbiota in EC/EH was associated with fatty acid and amino acid metabolism. In summary, our hypothesis-generating data indicate that the plastic-degrading bacteria Bacillus pseudofirmus and Stenotrophomonas rhizophila are over-represented within the endometrial lavage microbiota of women with EC/EH living in Taiwan. Whether this may be related to plastic pollution deserves further investigation.

Towards less invasive molecular diagnostics for endometrial cancer: massively parallel sequencing of endometrial lavage specimens in women attending for an office hysteroscopy.

We aimed to detect endometrial cancer (EC)-associated mutations in endometrial lavage specimens collected in an office setting and to compare the detected mutations with those identified in tissue samples. Participants included 16 women attending for an office hysteroscopy because of suspected EC between July 2020 and October 2021. Massively parallel sequencing was conducted using the targeted 72 cancer-associated genes. Endometrial lavage specimens, endometrial tissue samples, and blood samples were simultaneously sequenced to establish the concordance of genetic alterations. In this study, the vast majority of EC-associated mutations identified in lavage samples (R2 = 0.948) were identical to those detected in endometrial tissues. Of the 13 patients with EC, 12 (92.3%) had at least one mutation identified in endometrial lavage samples. Notably, no mutations in lavage samples were identified in the two patients with a previous history of EC but no actual endometrial lesions, supporting a high negative predictive value of the test. A patient previously diagnosed with EC and with current evidence of atypical hyperplasia showed persisting PTEN, PIK3R1, and KRAS mutations in her endometrial lavage specimen. PTEN was the most commonly mutated gene, followed by PIK3R1, ARID1A, PIK3CA, CTNNB1, and KRAS. In conclusions, our study provides pilot evidence on the actionability of uterine lavage samples sequencing to detect EC-associated mutations in women with suspected endometrial lesions. In a precision medicine framework, the high mutational concordance between uterine lavage samples and tissue specimens may help inform less invasive diagnostic protocols and the need for ongoing surveillance in patients with EC who wished for fertility-preserving treatment. KEY MESSAGES: • Sequencing of uterine lavage samples collected by office hysteroscopy is feasible. • Most EC mutations identified in lavage were identical to endometrial tissues. • Sequencing of uterine lavage samples may help inform diagnostic protocols for EC. • This approach can be used for recurrence surveillance in patients with EC.

Massively parallel sequencing of endometrial lavage specimens for the detection of cancer-associated mutations in atypical and non-atypical endometrial hyperplasia.

Background: Endometrial hyperplasia (EH), particularly with atypia, is considered an antecedent of endometrial adenocarcinoma. In this study, we aimed to apply massively parallel sequencing of endometrial lavage specimens for the detection of cancer-associated mutations in atypical (AEH) and non-atypical endometrial hyperplasia (NEH). The identified alterations were compared with those detected in tissue samples. Materials and methods: Endometrial lavage specimens and parallel biopsy samples (n = 11 for AEH and n = 9 for NEH) were obtained from 18 women (9 with AEH and 9 with NEH) who received an office hysteroscopy for suspected endometrial lesions. All samples were tested for somatic mutations in hotspot regions of 72 cancer-associated genes by massively parallel sequencing. Results: On analyzing sequencing data, the presence of at least one cancer-associated gene mutation was identified in 72.7 and 44.4% of endometrial lavage specimens obtained from women with AEH and NEH, respectively (p = 0.362, 95% confidence interval = 0.72-3.70). The concordance rates between mutations identified in endometrial lavage specimens and endometrial biopsies were 54.5 and 0% from women with AEH and NEH, respectively (p = 0.014). A patient with NEH harbored mutations in endometrial lavage with the same mutations found in the tissue specimen at low allele frequency below detection cutoff, raising the suspicion of missed focal atypia. Conclusion: Endometrial hyperplasia is characterized by a high burden of cancer-associated mutations, particularly in the presence of atypia. Our study, albeit performed with a relatively small number of samples, indicates that their detection by massively parallel sequencing of endometrial lavage is feasible. Our findings may allow tailoring of endometrial biopsies to the individual risk of AEH; additionally, they can pave the way toward less invasive surveillance protocols in patients with known EH.

A feasibility analysis of the ArcBlate MR-guided high-intensity focused ultrasound system for the ablation of uterine fibroids.

PURPOSE: Uterine fibroids are benign gynecologic tumors and commonly occur in women by the age of 50. Women with symptomatic uterine fibroids generally receive surgical intervention, while they do not favor the invasive therapies. To evaluate the feasibility and safety of a novel magnetic resonance-guided high-intensity focused ultrasound (MRgHIFU) modality, ArcBlate, in the treatment of uterine fibroids. METHODS: Nine patients with uterine fibroids and one patient with adenomyosis were treated with ArcBlate MRgHIFU. Tumor size and quality of life were evaluated postoperatively at 1 and 3 months by magnetic resonance imaging (MRI) and the 36-Item Short Form Survey (SF-36), respectively. RESULTS: All patients completed the ArcBlate MRgHIFU procedure and there were no treatment-related adverse effects either during the procedure or during the 3 months of follow-up. Despite limiting the ablation volume to under 50% of the treated fibroid volume as a safety precaution, tumor volumes were markedly reduced in four patients by 15.78-58.87% at 3-month post-treatment. Moreover, SF-36 scale scores had improved at 3 months from baseline by 2-8 points in six patients, indicating relief of symptoms and improved quality of life. CONCLUSION: This study evidence demonstrates the safety and feasibility of ArcBlate MRgHIFU and suggests its potential for treating uterine fibroids.

Molecular evidence for a clonal relationship between synchronous uterine endometrioid carcinoma and ovarian clear cell carcinoma: a new example of "precursor escape"?

Synchronous endometrial and ovarian carcinomas (SEOCs) that share the same endometrioid histology are generally considered as the result of metastatic spread from one organ to another. However, SEOCs with different histologies are regarded as distinct primary lesions that arise independently from each other. This study was undertaken to compare the mutational landscape of SEOCs with different histologies to confirm or refute the hypothesis of an independent origin. Four patients with synchronous uterine endometrioid carcinoma (UEMC) and ovarian clear cell carcinoma (OCCC) were examined. UEMCs were accompanied by endometrial hyperplasia/endometrioid intraepithelial neoplasia, whereas endometriosis was evident in two cases. Paired UEMC and OCCC specimens were subjected to mutation analysis with massively parallel sequencing. Surprisingly, we found that 50% (2/4) of paired SEOCs with different histologies shared the same somatic mutations, some of which localized in cancer driver genes. Clonality analyses indicated that these tumors were clonally related to each other. Notably, 75% (3/4) of the study patients had Lynch syndrome. The cancer-specific survival figures of patients with synchronous UEMCs and OCCCs were more favorable than those observed in a historical cohort of patients with isolated stage 2/3 OCCCs. Taken together, we set forth a potential explanation that considers clonally related SEOCs as a result of "precursor escape" - whereby precursor cells of endometrial cancer spread beyond the uterus to reach the pelvis and eventually evolve into an OCCC under an increasing mutational burden. KEY MESSAGES: • SEOCs characterized by different histologies are rare. • All cases of SEOCs were accompanied by endometrial hyperplasia. • Fifty percent of SEOCs were clonally related to each other. • Shared mutations in cancer driver genes were evident among SEOCs. • Clonally related SEOCs may be a result of "precursor escape." • Lynch syndrome is highly prevalent in patients with UEMC and synchronous OCCC. • The prognosis of synchronous UEMC and OCCC was favorable.

Use of human fibrin glue (Tisseel) versus suture during transvaginal natural orifice ovarian cystectomy of benign and non-endometriotic ovarian tumor: a retrospective comparative study.

BACKGROUND: To evaluate the use of a human fibrin glue (Tisseel) for minor bleeding control and approximation of ovarian defect during transvaginal natural orifice ovarian cystectomy (TNOOC) of benign and non-endometriotic ovarian tumors. METHODS: A total of 125 women with benign and non-endometriotic ovarian tumors who underwent TNOOC between May 2011 and January 2020: 54 with the aid of Tisseel and 71 with traditional suture for hemostasis and approximation of ovarian defect. Surgical outcomes such as length of surgery, operative blood loss, postoperative pain score, and postoperative hospital stay were recorded. Before and immediately (10 days) and at 6 months after the procedure, serum anti-Müllerian hormone (AMH) levels were also determined. RESULTS: Complete hemostasis and approximation of ovarian defect were achieved in all cases. No significant difference was noted in the operating time, operative blood loss, postoperative pain scores after 12, 24 and 48 h, length of postoperative stay, and baseline AMH levels between the two groups. The operation did not have a negative effect on the immediate and 6-month postoperative AMH levels in the suture group. However, the decline in the AMH levels was significant immediately after surgery in the Tisseel group, nevertheless, no significant difference was noted in the AMH levels at 6 months (3.3 vs. 1.7 mg/mL; p = 0.042, adjusted p = 0.210). CONCLUSION: The use of Tisseel in TNOOC of benign and non-endometriotic ovarian tumors without suturing the ovarian tissue is clinically safe and feasible.

Learning curve analysis of applying Seprafilm hyaluronic acid/carboxymethylcellulose membrane during laparoscopic hysterectomy.

This study was designed to evaluate the learning curve of applying Seprafilm (modified hyaluronic acid and carboxymethylcellulose; Genzyme, Cambridge, MA, USA) during laparoscopic hysterectomy or subtotal hysterectomy with or without adnexectomy. In this retrospective cohort study, 35 patients who underwent laparoscopic hysterectomy or subtotal hysterectomy with or without adnexectomy were enrolled. The Seprafilm was cut into 4 pieces, rolled up with a trimmed plastic sleeve and delivered through an incision wound made for the 5-mm ancillary trocar. The membrane was unrolled and placed on the rough surface after hysterectomy or subtotal hysterectomy with or without adnexectomy. The time from the insertion of the first piece of membrane into the abdominal cavity to the complete removal of the trimmed plastic sleeve was recorded. The median time for Seprafilm placement was 3 min. The learning curve was analyzed using the power-law method and suggested that 10 cases were required to achieve proficiency in the procedure. The presence of adnexectomy was significantly associated with the time required for Seprafilm placement (P < 0.001). Although Seprafilm placement is more complicated compared to the liquid and gel forms of anti-adhesion barriers, surgical proficiency seemed to be attained after 10 cases for an experienced surgeon.

Performing laparoscopic adenomyomectomy with the four-petal method.

OBJECTIVE: To demonstrate an innovative idea for a four-petal method for performing laparoscopic adenomyomectomy on a patient with focal-type adenomyosis. DESIGN: A step-by-step explanation of the technique with narrated video footage. SETTING: University hospital. PATIENT(S): A 38-year-old female with a 7 × 4 cm adenomyoma at the anterior uterine wall. INTERVENTION(S): Laparoscopic adenomyomectomy began with a cruciate incision to turn the adenomyoma into the shape of a blooming four-petal flower to fully expose the tumor and maximize the removal of adenomyotic tissue. During excision of the lesion, around a 1 cm thickness of the myometrium was preserved at the subendometrial region and around a 0.5 cm thickness of the serosa flap was also left in each "petal." Suture repair in the method introduced is different from closing the wound by approximation of myometrium to myometrium as in traditional myomectomy; instead, herein we repaired the adenomyomectomy wound by anchoring the serosal flap to the subendometrial tissue, with care taken to avoid dead space. MAIN OUTCOME MEASURE(S): Subjective clinical symptoms as well as serial ultrasonographic measurement of the uterine size, shape, and wall thickness. RESULT(S): The specimen removed was 92 g in weight. The symptoms have dramatically decreased since the procedure and dysmenorrhea improved from visual analog scale 8 to 1 postoperatively. Besides achieving satisfactory symptomatic relief, the ultrasonographic measurement of the myometrium was of adequate thickness (2.3 cm) after the operation and did not increase in a serial follow-up of 33 months. CONCLUSION(S): The four-petal method of adenomyomectomy with cruciate incision offers full exposure to the localized adenomyosis. It greatly facilitates a balance between the maximized resection of the lesions and tailored reserves of myometrium. Subsequent repair by anchoring the serosal flap to the subendometrial tissue ensures adequate thickness of the uterine wall after the operation.

Learning Curve Analysis of Transvaginal Natural Orifice Adnexal Surgery.

STUDY OBJECTIVE: This study was designed to evaluate the learning curve of transvaginal natural orifice surgery (NOS) for adnexal tumors based on the type of procedure (adnexectomy or cystectomy). DESIGN: Retrospective cohort study. SETTING: Tertiary-care university hospital. PATIENTS: One hundred thirty-six women with adnexal tumors. INTERVENTIONS: A series of 136 consecutive transvaginal NOS for adnexal tumor were performed between April 2011 and June 2016. Eighty-five patients (62.5%) had undergone cystectomy, and 51 patients (37.5%) had undergone adnexectomy. MEASUREMENTS AND MAIN RESULTS: The transvaginal NOS procedures included vaginal, endoscopic, single-port access techniques and were divided into 2 categories: adnexectomy and cystectomy. Operating time was electronically recorded and was defined as the time from the creation of a posterior colpotomy incision until the complete closure of the posterior colpotomy opening. The average operating time for the cystectomy and adnexectomy groups was 42.7 and 37.7 minutes, respectively (p = .015). The learning curve was analyzed using the cumulative summation method and showed that 36 cases were needed to achieve proficiency in transvaginal NOS for ovarian cystectomy. However, there was no significant cut-off point to determine the number of patients who had undergone adnexectomy. CONCLUSION: A well-trained gynecologic endoscopist can achieve surgical proficiency in transvaginal NOS cystectomy after 36 cases. It is suggested that the surgical transvaginal NOS procedure should begin with adnexectomy rather than with cystectomy to avoid initial technical challenges.

A Simple Technique for the Placement of Seprafilm, a Sodium Hyaluronate or Carboxymethylcellulose Absorbable Barrier, during Laparoscopic Myomectomy.

This report describes a simple technique using conventional instrumentation for the placement of Seprafilm, a sodium hyaluronate or carboxymethylcellulose absorbable barrier for adhesion prevention. A total of 378 women with uterine myomas undergoing laparoscopic myomectomies had 737 Seprafilm pieces placed. Seprafilm sheet was softened through exposure to room air for 5 minutes, cut into 4 pieces (length, 5-10 mm), rolled up alongside a plastic sheet cut from a camera drape cover, and gently placed at the right paracolic gutter. The Seprafilm pieces unfolded semiautomatically on release and were then placed on the uterus. The median time to apply per Seprafilm piece was 1 (range: 0.8-3.5) minute. We failed to place 16 pieces (16 of 737, 2.2%) in 11 patients. Virginal status, myoma weight, and the number of removed myomas were the risk factors of failed placement. Our technique for Seprafilm placement during laparoscopic myomectomy is simple and safe.

Learning curve analysis of transvaginal natural orifice transluminal endoscopic hysterectomy.

BACKGROUND: No data are available to assess the learning curve for transvaginal natural orifice transluminal endoscopic hysterectomy for non-prolapsed uteri in benign gynecologic diseases. The lack of exposure to transvaginal natural orifice transluminal endoscopic hysterectomy during training, in addition to a poorly defined learning curve, further deters interested physicians from applying this technique to daily practice. The aim of this study was to evaluate the learning curve and perioperative outcome of transvaginal natural orifice transluminal endoscopic hysterectomy by an experienced endoscopist. METHODS: A total of 240 cases of transvaginal natural orifice transluminal endoscopic hysterectomies with or without adnexectomy for various benign gynecologic diseases were included. Demographic data and various perioperative parameters were reviewed from the prospectively collected database. Operative time was set as a surrogate marker for surgical competency. The learning curve was evaluated using the cumulative sum method. RESULTS: The overall mean operative time (OT) was 76.5 min ± 22.4. Four unique phases of the learning curve were derived using cumulative sum analysis: the mean OT of phase I (the initial learning curve of 20 cases) was 86.3 ± 23.7 min, phase II (acquisition of competence of 80 cases) was 71.0 ± 21.4 min, phase III (proficiency and plateau of 80 cases) was 76.0 ± 20.4 min, and phase IV (post-learning in which more challenging cases were managed) was 81.3 ± 23.6 min. No major complications were encountered. One case in phase III converted to laparoscopy due to difficulty in performing anterior colpotomy. CONCLUSION: Our data demonstrated four distinct phases of the learning curve of transvaginal natural orifice transluminal endoscopic hysterectomy. In a well-trained endoscopist, surgical competence in transvaginal natural orifice transluminal endoscopic hysterectomy can be reached after 20 cases.