Uterine mesothelial cysts mimicking ovarian cysts in a primipara patient with a history of Cesarean section: A case report and review of the literature.

OBJECTIVE: We describe a rare case of uterine mesothelial cysts mimicking ovarian cysts in a primipara patient with a history of Cesarean section. CASE REPORT: A 39-year-old female patient with history of Cesarean section presented with dysmenorrhea. Sonography revealed that a hypoechoic and anechoic multicystic complex, which was located on the right side of the pelvic cavity, had infiltrated the adjacent posterior wall of the uterus, and it was preoperatively misdiagnosed as ovarian cysts with suspected endometrioma. Laparoscopic surgery revealed multiple cystic lesions filled with clear yellow fluid on the posterior uterine wall instead of the adnexa. Laparoscopic uterine cystectomy was performed, and the patient's recovery was uneventful. Pathohistological and immunohistochemical examinations confirmed the diagnosis of uterine mesothelial cysts. CONCLUSION: Uterine mesothelial cysts should be considered in the differential diagnosis of pelvic lesions. Increasing the awareness of this rare disease can contribute to improved evaluation, decision-making, and disease management.

Association of TRAIL receptor with phosphatase SHP-1 enables repressing T cell receptor signaling and T cell activation through inactivating Lck.

BACKGROUND: T cell receptor (TCR) signaling and T cell activation are tightly regulated by gatekeepers to maintain immune tolerance and avoid autoimmunity. The TRAIL receptor (TRAIL-R) is a TNF-family death receptor that transduces apoptotic signals to induce cell death. Recent studies have indicated that TRAIL-R regulates T cell-mediated immune responses by directly inhibiting T cell activation without inducing apoptosis; however, the distinct signaling pathway that regulates T cell activation remains unclear. In this study, we screened for intracellular TRAIL-R-binding proteins within T cells to explore the novel signaling pathway transduced by TRAIL-R that directly inhibits T cell activation. METHODS: Whole-transcriptome RNA sequencing was used to identify gene expression signatures associated with TRAIL-R signaling during T cell activation. High-throughput screening with mass spectrometry was used to identify the novel TRAIL-R binding proteins within T cells. Co-immunoprecipitation, lipid raft isolation, and confocal microscopic analyses were conducted to verify the association between TRAIL-R and the identified binding proteins within T cells. RESULTS: TRAIL engagement downregulated gene signatures in TCR signaling pathways and profoundly suppressed phosphorylation of TCR proximal tyrosine kinases without inducing cell death. The tyrosine phosphatase SHP-1 was identified as the major TRAIL-R binding protein within T cells, using high throughput mass spectrometry-based proteomics analysis. Furthermore, Lck was co-immunoprecipitated with the TRAIL-R/SHP-1 complex in the activated T cells. TRAIL engagement profoundly inhibited phosphorylation of Lck (Y394) and suppressed the recruitment of Lck into lipid rafts in the activated T cells, leading to the interruption of proximal TCR signaling and subsequent T cell activation. CONCLUSIONS: TRAIL-R associates with phosphatase SHP-1 and transduces a unique and distinct immune gatekeeper signal to repress TCR signaling and T cell activation via inactivating Lck. Thus, our results define TRAIL-R as a new class of immune checkpoint receptors for restraining T cell activation, and TRAIL-R/SHP-1 axis can serve as a potential therapeutic target for immune-mediated diseases.

Loss of LECT2 promotes ovarian cancer progression by inducing cancer invasiveness and facilitating an immunosuppressive environment.

Leukocyte cell-derived chemotaxin 2 (LECT2) is a multifunctional cytokine that can bind to several receptors and mediate distinct molecular pathways in various cell settings. Changing levels of LECT2 have been implicated in multiple human disease states, including cancers. Here, we have demonstrated reduced serum levels of LECT2 in patients with epithelial ovarian cancer (EOC) and down-regulated circulating Lect2 as the disease progresses in a syngeneic mouse ID8 EOC model. Using the murine EOC model, we discovered that loss of Lect2 promotes EOC progression by modulating both tumor cells and the tumor microenvironment. Lect2 inhibited EOC cells' invasive phenotype and suppressed EOC's transcoelomic metastasis by targeting c-Met signaling. In addition, Lect2 downregulation induced the accumulation and activation of myeloid-derived suppressor cells (MDSCs). This fostered an immunosuppressive microenvironment in EOC by inhibiting T-cell activation and skewing macrophages toward an M2 phenotype. The therapeutic efficacy of programmed cell death-1 (PD-1)/PD-L1 pathway blockade for the ID8 model was significantly hindered. Overall, our data highlight multiple functions of Lect2 during EOC progression and reveal a rationale for synergistic immunotherapeutic strategies by targeting Lect2.

Fertility and Pregnancy Outcomes after Fertility-Sparing Surgery for Early-Stage Borderline Ovarian Tumors and Epithelial Ovarian Cancer: A Single-Center Study.

This study examined treatment outcomes, including preserved fertility, menstrual regularity, and pregnancy outcomes, in patients with stage I epithelial ovarian cancer (EOC) or borderline ovarian tumors (BOTs) who underwent fertility-sparing surgery (FSS). Patients with stage I EOC and BOTs who were aged 18-45 years and underwent FSS between 2007 and 2022 were retrospectively reviewed. Significant differences between various subgroups in terms of disease recurrence, menstrual irregularity due to the disease, and pregnancy outcomes were analyzed. A total of 71 patients with BOTs and 33 patients with EOC were included. In the BOT group, the median age was 30 (range, 19-44) years. Recurrence occurred in eight patients, with one case exhibiting a malignant transformation into mucinous EOC. Among the 35 married patients with BOTs, 20 successfully conceived, resulting in 23 live births and 3 spontaneous abortions. A higher pregnancy rate was observed in those without prior childbirth (82.4%) than in those who had prior childbirth (33.3%). In the EOC group, the median age was 34 (range, 22-42) years. Recurrence occurred in one patient. Menstrual regularity was maintained in 69.7% of the patients. Among the 14 married patients in this group, 12 achieved a total of 15 pregnancies (including 2 twin pregnancies), 16 live births, and 1 spontaneous abortion. The results of the study confirmed that FSS is a favorable surgical option for young women with early-stage BOTs or EOC who wish to preserve their fertility. However, additional investigations are needed to validate these findings.

A method of laparoscopic treatment of large adnexal cysts - Two port trocar suction.

OBJECTIVE: The size of the adnexal cyst is a limitation to perform laparoscopic adnexal surgery. Large adnexal cysts may constrain the surgery space and may increase the risk of inadvertent cyst rupture during the surgery. Here, we offer a method to solve the difficulty in laparoscopic management of large adnexal cysts. MATERIALS AND METHODS: This is a retrospective study of 43 patients with large (≧10 cm) adnexal cysts, managed laparoscopically at one center from October 2016 to October 2019. All the surgeries were performed by an experienced laparoscopic surgeon. Malignancy was excluded before the surgeries according to the sonographic features. Cystectomy or salpingo-oophorectomy was decided according to the age, the sonographic pattern of the cyst and the patients' willingness. A 2 cm vertical incision was made at the umbilicus, and an open laparoscopy method was used to enter the peritoneal cavity. A wound protector was applied with a glove and two trocars being set up. The second wound was made at the left abdomen, and a 5 mm trocar was inserted. Then the cyst was punctured by means of the 5 mm trocar, and the content of the cyst was then soon aspirated by means of the air-flow hole of the trocar. Afterward, cystectomy or salpingo-oophorectomy was performed. Data are expressed as mean ± standard deviation unless stated otherwise. RESULTS: The mean operative duration was 54.7 ± 33.4 min, and the result was shorter than the previous study (P < 0.05, CI (-32.92, -12.38)) according to one sample t-test. Most estimated blood loss (EBL) was minimum. No obvious complication was found. CONCLUSION: Two-port trocar suction in laparoscopic management of large adnexal cysts is feasible after proper evaluation, and it takes short operative time.

Immune-Hot tumor features associated with recurrence in early-stage ovarian clear cell carcinoma.

Ovarian clear cell carcinoma (OCCC) is a distinct histotype of ovarian cancer, which usually presages a worse prognosis upon recurrence. Identifying patients at risk for relapse is an unmet need to improve outcomes. A retrospective cohort analysis of 195 early-stage OCCC patients diagnosed between January 2011 and December 2019 at National Taiwan University Hospital was conducted to identify prognostic factors for recurrence, progression-free survival (PFS) and overall survival (OS). Molecular profiling of tumors was performed in a case-controlled cohort matched for adjuvant therapy for biomarker discovery. Multivariate Cox proportional hazard model revealed that paclitaxel-based chemotherapy was associated with better PFS than nonpaclitaxel chemotherapy (HR = 0.19, P = .006). The addition of bevacizumab was associated with better PFS, compared to no bevacizumab (HR = 0.09, P = .02). Neither showed significant improvement in OS. Recurrence is associated with an Immune-Hot tumor feature (P = .03), the CTLA-4-high subtype (P = .01) and increased infiltration of immune cells in general. The Immune-Hot feature (HR = 3.39, P = .005) and the CTLA-4-high subtype (HR = 2.13, P = .059) were associated with worse PFS. Immune-Hot tumor features could prognosticate recurrence in early-stage OCCC.

Effectual surgical perineal reconstruction of malignant mucosal vulvar melanoma.

OBJECTIVE: To demonstrate a successful surgical treatment and reconstruction in a case of malignant mucosal vulvar melanoma. CASE REPORT: A 52-year-old woman had stage II bulky malignant mucosal vulvar melanoma and received wide surgical excision with partial vulvectomy. She underwent 2-steps reconstructive vulvoplasty and vaginoplasty with skin grafting 1 year after initial surgical treatment. There was no evidence of recurrence after 3 years of follow-up. CONCLUSION: Vulvar melanoma is a rare malignant neoplasm. Wide local excision with reconstruction can relieve pelvic discomfort and restore local function after the surgery.

Effect of Two-Port Laparoscopic Surgery on Pregnancy Outcomes of Patients with Concurrent Adnexal Masses.

Adnexal masses are common in pregnancy, with 2-10% of pregnancies presenting with an ovarian mass and approximately 1-6% of these masses being malignant. For suspected malignancy or masses with symptoms, surgery must be performed as early as possible. We retrospectively investigated the effect of two-port laparoscopic surgery on the outcomes of patients with concurrent adnexal masses between 2012 and 2019 (including large mucinous tumor, large teratoma, serous borderline tumor, and heterotopic pregnancy). Laparoscopic right partial oophorectomy was performed for a 27 cm ovarian mucinous tumor at a gestational age (GA) of 21 weeks, laparoscopic right oophorocystectomy for an 18 cm teratoma at a GA of 10 weeks, and laparoscopic left salpingo-oophorectomy for a 7 cm serous borderline tumor at a GA of 7 weeks after ultrasonographic confirmation of an intrauterine gestational sac with a fetal heartbeat. Laparoscopic excision of a tubal pregnancy was performed in a heterotopic pregnancy at a GA of 12 weeks with massive internal bleeding. Laparoscopic surgery is easier and safe to perform during early pregnancy because a smaller uterus allows for superior visualization. All of these patients had optimal postoperative recovery and normal spontaneous delivery at term. We discussed several aspects of treatment and delivery, namely treatment option (expectant management or surgery), surgery timing (early or advanced pregnancy), surgery type (laparoscopy or laparotomy), and delivery route (normal spontaneous delivery or cesarean section), in patients with concurrent adnexal tumors and their effects on pregnancy outcomes.

Sonographic features differentiating early-stage ovarian clear cell carcinoma from endometrioma with atypical features.

BACKGROUND: Ovarian clear cell carcinoma (OCCC) is the most common endometriosis-associated ovarian cancer. Ovarian endometriosis may present with atypical or malignant sonographic features and interfere with clinical judgment about whether definitive surgical intervention is required. OBJECTIVE: To compare the characteristics of endometrioma with atypical features and OCCC. METHODS: This study enrolled patients with pathologic diagnoses of either endometrioma or OCCC. For patients with endometrioma, only those with atypical features, defined as the presence of at least one of the following sonographic characteristics: cyst diameter of 10 ± 1 cm, multi-cystic lesions, any solid component or papillary structure, and blood flow of any degree, were included. RESULTS: Sixty-three patients had endometriomas with atypical features, while 57 patients had OCCC. Patients with endometriomas were younger (39.33 ± 7.04 years vs. 53.11 ± 9.28 years, P < 0.01), had smaller cysts (7.81 ± 2.81 cm vs. 12.68 ± 4.60 cm, P < 0.01), and had smaller solid components (0.93 ± 1.74 cm vs. 4.82 ± 3.53 cm, P < 0.01). In contrast, OCCCs were associated with loss of ground-glass echogenicity (6.3% vs 68.4%, P < 0.01). In multivariate analysis, advanced age (> 47.5 years), large cysts (> 11.55 cm), large solid components (size > 1.37 cm), and loss of ground-glass echogenicity were independent factors suggestive of malignancy. CONCLUSION: Advanced age, larger cyst sizes, larger solid component sizes, and loss of ground-glass echogenicity are major factors differentiating endometriomas from malignancies. For women in menopausal transition who have finished childbearing who present with endometrioma with atypical features, removal of the adnexa intact could be considered.

Laparoendoscopic two-site myomectomy (LETS-M) using conventional laparoscopic instruments and the glove-port technique.

PURPOSE: To evaluate the perioperative outcome of laparoendoscopic two-site myomectomy (LETS-M). METHODS: The medical records of 204 women receiving LETS-M in a tertiary referral center, including 183 surgeries performed by the experienced surgeon and 21 surgeries performed by 3 well-supervised trainees were retrospectively reviewed. RESULTS: The age of the participants was 39.3 ± 6.4 years. The mean diameter of the largest myoma and the mean number of myomas were 8.5 ± 2.2 cm and 1.7 ± 1.1, respectively. Thirty-one (15%) operations removed more than 2 myomas larger than 5 cm in diameter. The mean weight of the myomas was 281.1 ± 183.1 g. The operation time was 97.6 ± 40.2 min, and the intraoperative blood loss was 99.3 ± 115.2 mL. There were 3 (1%) cases of excessive blood loss (more than 500 mL) and 2 (1%) of postoperative hematoma. The only significant difference between the experienced surgeon and trainees was the operation time (92.3 ± 32.2 min vs. 141.2 ± 54 min, p < .001), while the myoma number, myoma diameter, myoma weight, and intraoperative blood loss were not significantly different. The operation time did not differ among different myoma locations. In multivariate analysis, virginity, myoma number, more than 2 large myomas, and myoma size were independent variables for longer operation times. No patient experienced any major complications. CONCLUSION: LETS-M using conventional laparoscopic equipment is a minimally invasive surgical method that is safe, effective, and easy to learn for managing uterine myoma. It is useful to achieve a favorable perioperative outcome with acceptable operation time.

Analyzing the learning curve of vaginal pelvic reconstruction surgery with and without mesh by the cumulative summation test (CUSUM).

Women who underwent vaginal pelvic reconstructive surgery with or without mesh consecutively between 2004 and 2018 were retrospectively analyzed to determine the learning curve in vaginal pelvic reconstructive surgery. With cumulative summation (CUSUM) analysis of surgical failure and operation time, we assessed the learning curve of vaginal pelvic reconstructive surgery, including sacrospinous ligament fixation, anterior colporrhaphy, posterior colporrhaphy, and optional vaginal hysterectomy with or without mesh placement. The study is based on two individual surgeons who performed vaginal pelvic reconstructive surgery with or without mesh. Two hundred and sixty-four women with stage III or IV pelvic organ prolapse underwent vaginal pelvic reconstructive surgery by surgeons A or B. The median follow-up time of 44 months ranged from 24 to 120 months. Surgical proficiency was achieved in 32-33 vaginal pelvic reconstructive surgery procedures without mesh and 37-47 procedures in the same surgery with mesh. The total surgical success rates for surgeons A and B were 82.2% and 94.1%, with median follow-up times of 60 and 33 months, respectively. More procedures were needed for the learning curve of vaginal pelvic reconstructive surgery with mesh. Having crossed the proficiency boundary, the surgical success rate and operation time were improved.

Real-World Evaluation of Modern Adjuvant Radiotherapy in Women with Stage IB Endometrial Cancer.

The optimal adjuvant treatment for stage IB endometrial cancer remains undefined. We investigated the benefit of modern adjuvant radiotherapy for women with stage IB endometrial cancer. We retrospectively reviewed patients with surgically staged, pure stage IB endometrioid adenocarcinoma (2010 to 2018). Adjuvant modern radiotherapy consists of external-beam radiotherapy (EBRT) by intensity, volumetric-modulated arc radiotherapy, or image-guided vaginal brachytherapy (VBT). The study included 180 stage IB patients. Patients with grade 3 diseases had frequent aggressive histology patterns (lymphovascular space invasion (LVSI); low uterine segment involvement) and experienced significantly shorter recurrence-free survival (RFS) and overall survival (OS) than patients with grade 1/2 diseases. Adjuvant modern radiotherapy decreased the incidence of acute/chronic grade ≥2 gastrointestinal toxicity. In IB grade 1/2 patients, EBRT significantly lengthened survival (RFS/OS); patients with age >60 years, myometrial invasion beyond the outer third, or LVSI benefited the most from EBRT. EBRT also significantly improved survival (RFS/OS) in IB grade 3 patients, where patients with bulky tumors or LVSI benefited the most from EBRT. Therefore, EBRT may be beneficial for all stage IB patients.

Single incision laparoscopic surgery using conventional laparoscopic instruments versus two-port laparoscopic surgery for adnexal lesions.

Single incision laparoscopic surgery (SILS) has emerged as least invasive interventions for gynecologic disease. However, SILS is slow to gain in popularity due to difficulties in triangulation and instrument crowding. Besides, the costly instruments may influence patients' will to have this procedure, and limit other medical expense as well. To optimize outcome and reduce cost, the objective of this study is to evaluate the feasibility and safety for patients undergoing adnexal surgeries using conventional laparoscopic instruments with SILS (SILS-C), and to compare with those of patients subject to TP using conventional laparoscopic instruments (TP-C). This is a retrospective case-control study. The data dated from April 2011 to April 2018. Patients who received concomitant multiple surgeries, were diagnosed with suspected advanced stage ovarian malignancy, or required frozen sections for intraoperative pathologic diagnosis were excluded. Demographic data, including the age, body weight, height, previous abdominal surgery were obtained. The surgical outcomes were compared using conventional statistical methods. 259 patients received SILS-C. The operating time was 63.83 ± 25.31 min. Blood loss was 2.38 ± 6.09 c.c. 58 patients (24.38%) needed addition of port to complete surgery. 384 patients received TP-C. Compared with SILS-C, the operating time was shorter (57.32 ± 26.38 min, OR = 0.984, CI = 0.975-0.992). The patients were further divided into unilateral or bilateral adnexectomy, and unilateral or bilateral cystectomy. Other than the operating time in unilateral cystectomy (66.12 ± 19.5 vs. 58.27 ± 23.92 min, p = .002), no statistical differences were observed in the subgroup analysis. Single incision laparoscopic surgery using conventional laparoscopic instruments is feasible and safe as initial approach to adnexal lesions. In complex setting as unilateral cystectomy or pelvic adhesions, two-port access may be considered.

Two-port access for laparoscopic surgery for endometrial cancer using conventional laparoscopic instruments.

Minimally invasive surgery is the first-line management for endometrial cancer. The role of 2-port access laparoscopy (TPA) has been underestimated. Compared to conventional laparoscopic surgery (CL), TPA is associated with smaller total incision size and less postoperative pain. Compared to single-incision laparoscopic surgery, no specific instruments and surgical techniques are needed. This study primarily evaluated the surgical and pathologic outcomes of TPA with conventional instruments, and additionally evaluated the surgeon's learning curve. Consecutive patients who underwent TPA and CL for endometrial cancer between 2015 and 2019 were included. Baseline characteristics were recorded. In total, 148 patients (TPA, 89; CL, 59) were identified. The baseline characteristics were similar, except for a greater proportion of patients in the CL group receiving para-aortic lymph node dissection (5.62% vs. 35.59%, P < 0.01). The mean operation time was significantly less in the TPA group (152.09 vs. 187.15 min; P < 0.01). Both the groups had comparable 5-year progression-free survival (TPA, 86.68%) and 5-year overall survival rates (TPA, 93.24%). Analysis of the learning curve showed that the operation time decreased after 3-4 procedures. TPA using conventional laparoscopic instruments for endometrial cancer is feasible and is easily accessible to patients and surgeons.

Prolapsed epiploica of bowel after robotic hysterectomy: A case report.

PURPOSE: Vaginal cuff dehiscence with evisceration was defined as expulsion of intraperitoneal organs through the separated incision. Prolapsed epiploica of the colon is a rare complication after hysterectomy. The most common organ to prolapsed out from the dehiscence vaginal cuff is terminal ileum. We reported the first known case of prolapsed epiploica of the colon after robotic hysterectomy. CASE: This is a case who had prolapse of a vaginal tumor after sexual intercourse 5 months after robotic hysterectomy. Vaginal tumor resection and primary closure were performed successfully without complications. The final pathology revealed fat prolapse with foreign body reaction and confirmed prolapse of epiploica of the colon. Being aware of the risk factors and patients who are more likely to develop this complication is essential in making the correct diagnosis in time. MAJOR CONCLUSION: Patients with a higher risk of vaginal cuff dehiscence are advised to avoid sexual activity for a longer period of time. Surgical intervention is the primary treatment. Prolapsed epiploica of the colon should be kept in mind for those who have undergone hysterectomy in order to provide appropriate treatment in time.

Long-term follow-up of 453 patients with pelvic organ prolapse who underwent transvaginal sacrospinous colpopexy with Veronikis ligature carrier.

Sacrospinous ligament fixation (SSLF) is one of the most utilized surgeries in the management of pelvic organ prolapse (POP). We conducted a large-series study of SSLF in a tertiary center by an experienced urogynecologic team. The 453 women with POP who underwent SSLF at National Taiwan University Hospital in the period from 2002 to 2015 are reviewed. All patients received unilateral SSLF with Veronikis ligature carrier. Concomitant anterior colporrhaphy was performed in 75.3% of the cases and posterior colporrhaphy in 78.6%. The mean operation time was 92.3 ± 31.5 minutes. The intraoperative blood loss was 92.3 ± 91.4 ml. The objective cure rate was 82.5%, and 79 (17.5%) patients recurred. The Kaplan-Meier recurrence-free analysis showed a steep decline during the first postoperative year, and the yearly number of recurrent patients decreased as the follow-up period proceeded. A comparison of the site of recurrence found that anterior compartment prolapse was the most common with 57 cases (12.6%). Paravaginal repair is frequently implemented in the management of recurrent anterior prolapse. In conclusion, SSLF provides excellent support to the apex compartment, and our long-term results show that the anterior compartment is the most commonly encountered type of POP recurrence.

Comparison of uterine scarring between robot-assisted laparoscopic myomectomy and conventional laparoscopic myomectomy.

This study compared uterine wound healing after robot-assisted laparoscopic myomectomy (RM) and laparoscopic myomectomy (LM). Ultrasound was used to evaluate the scar repair of uterine wounds at 1, 3, and 6 months postoperatively. Ninety-three RM and 110 LM patients were enrolled. More myomas excised using RM were type 1∼type 3(51.1%) and more myomas excised using LM were type 4∼type 6(54.2%), p < .001. Both groups had myomas of similar size (RM vs. LM, 9.0 vs. 8.4 cm, p = .115) and weight (RM vs. LM, 322 vs. 274 g, p = .102). The mean myoma number was significantly larger in RM patients than LM patients (RM vs. LM, 3.3 vs. 1.8, p < .001). Significantly more patients were found to have haematomas in the LM than the RM group (RM vs. LM, 0 vs. 6, p = .032); two in type 3, two in type 4 and two in type 8 myomas. Four small haematomas spontaneously resolved at the 3rd month, and a large one resolved at the 9th month postoperatively. One haematoma caused pelvic infection and a 7-cm peritoneal inclusion cyst during sonographic follow up. RM resulted in fewer postoperative haematomas and may result in superior uterine repair relative to LM after excision of symptomatic type 3, type 4 and type 8 myomas. RM is suggested for these patients, especially those considering future pregnancy.IMPACT STATEMENTWhat is already known on this subject? Reconstructive suturing and uterine wound healing are the main challenges when performing laparoscopic myomectomy (LM), and spontaneous uterine rupture during pregnancy following LM has been reported because of its limitations in multilayer closure of the myoma bed. Robot-assisted laparoscopic myomectomy (RM) has improved visualisation and EndoWrist movements resulted in adequate multilayered suturing, which may overcome the technical limitations of reconstructive suturing in conventional LM.What do the results of this study add? We evaluated postoperative uterine scarring after RM and LM using ultrasound and found RM resulted in fewer postoperative haematomas, which result in superior uterine wound repair, relative to LM after excision of symptomatic type 3, type 4 and type 8 myomas.What are the implications of these findings for clinical practice and/or further research? RM is suggested for symptomatic type 3, type 4 and type 8 myomas because of superior uterine wound repair, especially those considering future pregnancy.

Activation of STAT3 and STAT5 Signaling in Epithelial Ovarian Cancer Progression: Mechanism and Therapeutic Opportunity.

Abstract: Epithelial ovarian cancer (EOC) is the most lethal of all gynecologic malignancies. Despite advances in surgical and chemotherapeutic options, most patients with advanced EOC have a relapse within three years of diagnosis. Unfortunately, recurrent disease is generally not curable. Recent advances in maintenance therapy with anti-angiogenic agents or Poly ADP-ribose polymerase (PARP) inhibitors provided a substantial benefit concerning progression-free survival among certain women with advanced EOC. However, effective treatment options remain limited in most recurrent cases. Therefore, validated novel molecular therapeutic targets remain urgently needed in the management of EOC. Signal transducer and activator of transcription-3 (STAT3) and STAT5 are aberrantly activated through tyrosine phosphorylation in a wide variety of cancer types, including EOC. Extrinsic tumor microenvironmental factors in EOC, such as inflammatory cytokines, growth factors, hormones, and oxidative stress, can activate STAT3 and STAT5 through different mechanisms. Persistently activated STAT3 and, to some extent, STAT5 increase EOC tumor cell proliferation, survival, self-renewal, angiogenesis, metastasis, and chemoresistance while suppressing anti-tumor immunity. By doing so, the STAT3 and STAT5 activation in EOC controls properties of both tumor cells and their microenvironment, driving multiple distinct functions during EOC progression. Clinically, increasing evidence indicates that the activation of the STAT3/STAT5 pathway has significant correlation with reduced survival of recurrent EOC, suggesting the importance of STAT3/STAT5 as potential therapeutic targets for cancer therapy. This review summarizes the distinct role of STAT3 and STAT5 activities in the progression of EOC and discusses the emerging therapies specifically targeting STAT3 and STAT5 signaling in this disease setting.