Early outcomes of three new robotic surgical systems in patients undergoing hysterectomy.

New robot models, such as hinotori™, da Vinci SP™, and Hugo™, have been introduced in Japan. This study examined the surgical outcomes of these models in patients from the initial stages of their introduction to the present day.We retrospectively reviewed 36 patients with endometrial cancer or benign gynecologic disease, who underwent robotic hysterectomy using da Vinci SP™, hinotori™, or Hugo™ between March 2023 and March 2024.Robotic hysterectomy was performed using hinotori™ in 10 patients, da Vinci SP™ in 16 patients, and Hugo™ in 10 patients. No significant differences were observed in the characteristics of the patients subjected to surgery using these models. The total operative time was 123.0 min (93-144 min) for hinotori™, 95.0 min (79-165 min) for da Vinci SP™, and 98.5 min (74-177 min) for Hugo™. The total operative time of hinotori™ was significantly longer than that of the other two models (p = 0.031). No differences were observed among the robot systems with respect to complications during or after surgery and the intensity of postoperative pain.Differences in the surgical time were noted depending on the model used. It has been proven that surgeons who are already proficient in performing robotic surgery with da Vinci Xi™ can safely perform surgeries with the new models.

Surgical Outcomes of da Vinci Xi™ and da Vinci SP™ for Early-Stage Endometrial Cancer in Patients Undergoing Hysterectomy.

Objectives: This study aimed to evaluate and compare the feasibility and outcomes of two robotic hysterectomy (da Vinci Xi™ vs. da Vinci SP™) systems without lymph node dissection in patients with early-stage endometrial cancer, and assess the postoperative recurrence rate and overall survival of patients. Methods: A retrospective review of 84 patients who underwent robotic hysterectomy for endometrial cancer (stage 1A) was conducted. Surgical procedures, patient characteristics, intraoperative measures, and postoperative outcomes were statistically analyzed. A single gynecologist performed all surgeries. Results: Patient characteristics, average age, and body mass index showed no significant differences between the two models. The total operative time was significantly shorter with da Vinci SP™. Recurrence was identified in only one patient operated on with da Vinci Xi™. All patients were alive during analysis, with a median overall survival of 38 and 9 months for da Vinci Xi™ and da Vinci SP™, respectively. Conclusions: Robotic hysterectomy without lymph node dissection appears to be a safe and effective approach for patients with early-stage endometrial cancer. The da Vinci SP offers the advantage of shorter operative times than the da Vinci Xi™. These findings support the consideration of robotic surgery as a viable option for selected patients.

Current treatment strategies for ovarian cancer in the East Asian Gynecologic Oncology Trial Group (EAGOT).

Ovarian cancer, notable for its severe prognosis among gynecologic cancers, has seen substantial progress in treatment approaches recently. Enhanced protocols in chemotherapy and the introduction of poly (ADP-ribose) polymerase (PARP) inhibitors for maintenance therapy have markedly improved outcomes for patients with specific genetic profiles, such as those positive for BRCA mutations or exhibiting homologous recombination deficiency (HRD). Additionally, the method of intraperitoneal chemotherapy administration has emerged as a valuable alternative to traditional transvenous routes, showing promise for wider clinical adoption. The field of surgery has also evolved, with increasing exploration into the benefits and feasibility of laparoscopic methods over more invasive traditional surgeries, aiming for complete tumor removal but with reduced patient impact. The hereditary nature of ovarian cancer underscores the importance of genetic testing, which has become integral in tailoring treatment strategies, particularly in determining suitability for PARP inhibitors. The formation of the East Asian Gynecologic Oncology Trial Group (EAGOT) aims to optimize treatment across Japan, Korea, China, and Taiwan. The ovarian cancer committee of EAGOT shared the current policies, focusing on 5 topics: 1) strategies for maintenance therapy after initial surgery and chemotherapy, 2) drug regimens for platinum-sensitive and platinum-resistant recurrence, 3) intraperitoneal chemotherapy, 4) laparoscopic surgery as an alternative to laparotomy, and 5) current status of genetic testing (BRCA, HRD, and panel tests) for ovarian cancer and its prospects. EAGOT's multi-national trials aim to harmonize these evolving treatment strategies, ensuring that the latest and most effective protocols are accessible across the region, thereby significantly impacting patient outcomes in East Asia.

Hybrid Train-The-Trainer course for the Fundamental Use of Surgical Energy certificates improves self-confidence in knowledge of surgical energy and develops teaching skills: a feasibility study.

BACKGROUND: Several well-trained expert instructors who completed the "Train-The-Trainer (TTT)" course are required to disseminate the safe use of surgical energy devices, which can be learned through the Fundamental Use of Surgical Energy (FUSE) program. This study aimed to explore whether the hybrid FUSE TTT course is feasible and effective, which can improve teaching skills of surgical energy. METHODS: The hybrid TTT course, which was designed to train FUSE-certified personnel as instructors, comprised three virtual sessions spread over 5 h in total and a 1-day in-person training, followed by a 100-min FUSE electrosurgery hands-on workshop in practice as an instructor. The participants reported on self-confidence regarding knowledge of various energy devices or adverse events before, immediately after, and 6 months after the course. Participants and experienced FUSE instructors assessed the trainees' presentation skills at the beginning of the in-person training and after the hands-on workshop. The primary outcomes were the feasibility and completion rate of the entire course. RESULTS: Seventeen participants completed the entire couse; most (94%) were satisfied with the course. Self-confidence in knowledge about various contents improved significantly: the fundamentals of electrosurgery (post, p < 0.001; 6 months, p = 0.01), mechanism and prevention of adverse events (post, p = 0.001; 6 months, p = 0.04), monopolar instruments (post, p = 0.002; 6 months, p = 0.01), bipolar instruments (post, p = 0.01; 6 months, p = 0.06), and integration with other medical devices (post, p = 0.006; 6 months, p = 0.02). The presentation skill index scores of self- and peer assessments improved after the in-person training (self-assessment [pre 44 vs. post 56, p < 0.001], peer assessment [pre 39 vs. post 68, p < 0.001]). CONCLUSIONS: The hybrid TTT course can provide FUSE-certified personnel with an improved self-confidence concerning knowledge of surgical energy and improve their presentation skills with midterm retention. This can help build trainees' self-confidence as instructors.

Diagnosis and Methods of Repair for a Uteroperitoneal Fistula (UPF) Formed After Gynecological Surgeries.

A uteroperitoneal fistula (UPF) is a rare disorder that can lead to infertility and has never been reported. UPFs can cause infertility and perinatal complications. A 34-year-old woman (gravida 0) with a history of three gynecological surgeries using a uterine manipulator was diagnosed with a UPF using hysteroscopy and hysterosalpingography. She underwent laparoscopic uterine repair as an infertility treatment. The uterine perforation may have been caused by uterine manipulator insertion or suture failure in the myometrium during her previous laparoscopic myomectomy and cystectomy procedures. The UPF disappeared after the current surgical treatment. The complications of UPFs include infection, infertility, ectopic pregnancy, and uterine rupture. We expected that the presence of a fistula would increase the risk of impaired fertilization, implantation failure, and ectopic pregnancy. This case report contributes valuable insights into the diagnosis of UPFs and their laparoscopic repair.

Laparoscopic retrovesical lower uterine segment bypass for hysterectomy with previous caesarean section: Hung Up the Bladder Bypass (HUBB) technique.

Patients with a history of cesarean section and a highly adherent bladder may have difficulty in bladder dissection and may suffer damage. It may also be difficult to orient the patient for repair in the event of damage. In such cases, dissection from the side between the bladder and cervix is a good way to avoid complication. This video reviews the steps of the HUBB technique procedure, provides tips and tricks for performing a successful adhesiolysis, and illustrates the procedure's adaptability. The first is the identification of the uterine artery and its position. Step2, a Laparoscopic retrovesical lower uterine segment bypass is created. Step3 a Hung Up the Bladder Bypass is created, the bladder is completely dissected. Step4, an adhesiolysis and leak test is performed. In this report, we would like to introduce a technique for creating a retrovesical lower uterine segment bypass using a laparoscope and traction on the bypass to dissect the bladder.

Clinical characteristics and prognostic factors of endometrial stromal sarcoma and undifferentiated uterine sarcoma confirmed by central pathologic review: A multi-institutional retrospective study from the Japanese Clinical Oncology Group.

OBJECTIVES: Low-grade and high-grade endometrial stromal sarcomas (LGESS and HGESS) and undifferentiated uterine sarcomas (UUS) are rare tumors whose pathological classification and staging system have changed recently. These tumors are reported to contain fusion genes. We aimed to clarify the genetic background, clinical features, prognostic factors, and optimal therapy of these tumors using a new classification and staging system. METHODS: We analyzed the clinical features and prognostic information of 72 patients with LGESS, 25 with HGESS, and 16 with UUS using central pathological review. Estrogen and progesterone receptors (PgRs) were examined by immunohistochemistry. JAZF1-SUZ12 and YWHAE-NUTM2A/B gene fusions were tested using real-time polymerase chain reaction. RESULTS: The 5-year overall survival (OS) rates of LGESS, HGESS, and UUS were 94%, 53%, and 25%, respectively. In LGESS, stage IV, incomplete surgery, and absence of PgR were associated with poor OS. The presence of JAZF1-SUZ12 fusion gene was not associated with OS. In HGESS, the relationship between stage and prognosis was unclear. None of the 3 patients with YWHAE-NUTM2A/B fusion gene died during follow-up. Adjuvant chemotherapy was associated with a favorable OS. Incomplete resection of UUS was associated with poor OS; however, residual tumors frequently occurred. Although most patients underwent adjuvant chemotherapy, their prognosis was extremely poor even in stage I disease. CONCLUSIONS: Prognosis of LGESS is generally good; however, stage IV, incomplete surgery, and PgR-negative tumors are associated with poor prognosis. Adjuvant chemotherapy may be useful for HGESS. Prognosis of UUS is extremely poor, even with adjuvant chemotherapy.

Therapeutic efficacy of a four-year treatment with eribulin in a patient with uterine leiomyosarcoma: A case report.

Uterine leiomyosarcoma (LMS) is a gynecological malignancy with an extremely poor prognosis. Multiple new therapeutic agents, including pazopanib, trabectedin, and eribulin, have been clinically applied to treat uterine LMS, and their therapeutic effects are expected. We encountered one patient with advanced recurrent uterine LMS who achieved a partial response to a four-year treatment with eribulin. A 31-year-old woman was diagnosed with stage 2B LMS. After the first recurrence, Gemcitabine, Docetaxel (GD) therapy was administered, and complete response (CR) was achieved. However, 2 years and 10 months later, recurrence occurred at the vaginal cuff, and GD therapy and doxorubicin hydrochloride were administered, resulting in CR. Five months later, she experienced another recurrence at the same location and was treated with eribulin. To date, 53 courses of eribulin have been administered and are currently ongoing. Maintaining low neutrophil-to-lymphocyte ratio and low platelet-to lymphocyte ratio in this manner is considered to be one of the reasons why eribulin continues to be effective. We encountered a rare case in which eribulin was administered for the longest period of time, and produced an observable effect in uterine LMS.

Cervical conization with endoCUT mode applying gastrointestinal endoscopic polypectomy technique.

OBJECTIVE: To show how endoCUT mode can be safely managed with cervical conization. METHODS: Demonstration of the technique and explanation of endoCUT and soft coagulation mode with narrated video footage. Cervical conization is a therapeutic and diagnostic procedure performed for the diagnosis of cervical intraepithelial lesions and cervical cancer. Specific. METHODS: include cold scalpel, ultrasonically activated device and laser, and loop electrosurgical excision procedure (LEEP), which involves transpiration and partial excision. The endoCUT mode and soft coagulation in VIO3® (ERBE, Tübingen, Germany) were used to perform cervical conical resection safely and at low cost. The endoCUT mode was originally developed for polypectomy in gastrointestinal endoscopy, where no counter traction can be applied. RESULTS: The endoCUT mode approach to cervical conization with several key strategies to minimize blood loss and ensure safety: 1) incisions can be made in close contact; 2) resection can be performed with minimal contact with the lesion; 3) control of bleeding from the resected transection by soft coagulation; and 4) low running cost of endoCUT mode. CONCLUSION: Conventionally, cervical conical resection has been performed by using a device capable of making a close incision (cold scalpel, ultrasonically activated device and laser, and LEEP etc.), but there have been issues with bleeding control and cost. Here, we present a new technique using the endoCUT mode and several strategies for safe and effective resection.

Graft Failure after Uterus Transplantation in 16 Recipients: A Review.

Uterus transplantation (UTx) is now an alternative to surrogacy and adoption for women with uterine factor infertility to have children; however, there are still unresolved clinical and technical issues. One of these is that the graft failure rate after transplantation is somewhat higher than that of other life-saving organ transplants, which is a critical concern. Herein, we summarize the details of 16 graft failures after UTx with living or deceased donors using the published literature in order to learn from these negative outcomes. To date, the main causes of graft failure are vascular factors (arterial and/or venous thrombosis, atherosclerosis, and poor perfusion). Many recipients with thrombosis develop graft failure within one month of surgery. Therefore, it is necessary to devise a safe and stable surgical technique with higher success rates for further development in the UTx field.

Mailing human papillomavirus self-sampling kits to women under-screened for cervical cancer improved detection in cervical cancer screening in a general population study in Japan.

BACKGROUND: One cause of the increase in cervical cancer rates in Japan is the long-term stagnation in the cervical cancer screening consultation rate. Therefore, improving the screening consultation rate is of urgent concern to reduce cervical cancer incidence. Self-collected human papilloma virus (HPV) tests have been successfully adopted in several countries, such as the Netherlands and Australia, as a measure of individuals who have not undergone cervical cancer screening in national programs. This study aimed to verify whether self-collected HPV tests presented an effective countermeasure for individuals who had not undergone the recommended cervical cancer screenings. METHODS: This study was conducted from December 2020 to September 2022 in Muroran City, Japan. The primary evaluated endpoint was the percentage of citizens who underwent cervical cancer screening at a hospital with positive self-collected HPV test results. The secondary endpoint was the percentage of included participants who were diagnosed with cervical intraepithelial neoplasia (CIN) or higher among those who visited a hospital and underwent cervical cancer screening. RESULTS: The included study participants were 7,653 individuals aged 20-50 years with no record of previous cervical cancer examination in the past 5 years. We mailed these participants information on self-administered HPV tests as an alternative screening procedure and sent the kit to 1,674 women who requested the test. Among them, 953 returned the kit. Among the 89 HPV-positive individuals (positive rate, 9.3%), 71 (79.8%) visited the designated hospital for an examination. A closer examination revealed that 13 women (18.3% of hospital visits) had a CIN finding of CIN2 or higher, among whom one each had cervical cancer and vulvar cancer, eight presented with CIN3, and three presented with CIN2; two cases of invasive gynecologic cancer were also identified. CONCLUSIONS: We conclude that the self-collected HPV tests showed a certain efficacy as a measure of individuals who had not undergone the recommended cervical cancer screening. We devised ways to have the unexamined patients undergo HPV testing and ensure that HPV-positive individuals visited the hospital. Despite a few limitations, our findings suggest the effectiveness of this public health intervention.

A mixed-method evaluation of cadaver surgery training for gynecologic oncology.

AIM: Traditional surgical training techniques with using patients, and new advances with live animals, artificial models, and simulation methods have several shortcomings. There are a few reports on the usefulness of cadaver surgery training (CST) in gynecology. Herein, we used a mixed-method evaluation to qualitatively and quantitatively explore the educational efficacy of CST by conducting CST programs at the Sapporo Medical University, Japan. METHODS: In 2020, we conducted two CST programs with 45 participants-13 residents, 8 specialists recognized by Japan Society of Obstetrics and Gynecology, 23 certified endoscopists recognized by Japan Society of Gynecology and Obstetrics Endoscopy and Minimally Invasive Therapy, 15 specialists recognized by Japan Society of Gynecologic Oncology, and 14 certified endoscopists cum oncology. Three participants observed the procedure virtually and 42 were physically present. Laparoscopic radical hysterectomy and pelvic exenteration were performed on five Thiel-embalmed cadavers. Participants were asked to complete pre- and post-training surveys that included qualitative questions, concerning the purpose and cost of CST, and quantitative questions, testing anatomical knowledge. RESULTS: We observed that the rate of score improvement to the quantitative questions increased from 58.6% pre-CST to 75.6% post-CST. Furthermore, oncology specialists and those who performed more surgeries and faced more complications during surgeries recorded high percentage of correct answers. Multiple regression analysis statistically confirmed these results. CONCLUSIONS: This study confirmed the educational efficacy of CST.

Human papillomavirus testing and cytology using physician-collected uterine cervical samples vs. self-collected vaginal samples and urine samples.

BACKGROUND: Human papillomavirus (HPV) testing using self-collected vaginal samples and urine samples is convenient and effective for improving the screening rate. But, to serve as an alternative cervical cancer screening technique, such tests must offer sensitivity equivalent to the HPV testing of physician-collected cervical samples. To examine the effectiveness of HPV testing using self-collected samples and urine samples, we compared the results of HPV testing using these samples with those of HPV testing using physician-collected samples and cytological examinations. METHODS: The study population included 300 women (age: 20-50 years) with abnormal cervical cytology. The results of HPV testing using self-collected samples and urine samples and physician-collected samples and cervical cytology were compared. RESULTS: For all HPV types, the κ-value was 0.773 for physician- and self-collected samples and 0.575 for physician-collected and urine samples. The κ-value for HPV type 16-positive samples was 0.988 for physician- and self-collected samples and 0.896 for physician-collected and urine samples. The κ-value for HPV type 18-positive samples was 0.856 for physician- and self-collected samples and 0.831 for physician-collected and urine samples. For other HPV types, the value was 0.809 for physician- and self-collected samples and 0.617 for physician-collected and urine samples. CONCLUSIONS: The obtained results were consistent between physician- and self-collected samples as well as between physician-collected and urine samples. Considering that the agreement rate was particularly high for the high-risk HPV types 16 and 18, HPV testing using physician-collected samples, self-collected samples, and urine samples was equally effective for the types with high carcinogenicity.

Pathological classification of desmoplastic reaction is prognostic factor in cervical adenocarcinoma.

Desmoplastic reaction (DR) and inflammation are significant pathological manifestations of tumorigenesis in several cancers. However, the correlation between these stromal reactions and cervical adenocarcinoma has been poorly documented. This investigation elucidated whether DR is a prognostic indicator in early cervical adenocarcinoma patients. Fifty-nine patients with early stage cervical adenocarcinoma (stages I/II) were included in the study. DR was divided into three groups, mature, intermediate, and immature, based on the presence of myxoid stroma and hyalinized keloid-like collagen. Inflammatory cell responses were classified as mild, moderate, and severe. Those stromal reactions were separately evaluated in the invasion front stroma and intratumoral stroma. In both the intratumor and invasion front stroma, intermediate/immature DR was correlated with tumor size, T stage, N stage, lymphovascular invasion, and parametrial infiltration (p < 0.001 to p < 0.05). In addition, in the intratumoral stroma, intermediate/immature DR led to short relapse-free survival and overall survival (p < 0.001). In the invasion front stroma, inflammatory cell responses were associated with DR immaturity and FIGO stage (p < 0.01). These results suggest that the classification of DR maturity is a potential prognostic biomarker in early stage cervical adenocarcinoma patients. DR can be evaluated by routine H&E staining without immunohistochemistry, making it convenient and economical in clinical practice.

Radical Vaginal Trachelectomy.

Recently, radical vaginal hysterectomy (RVH) has developed into laparoscopically assisted radical vaginal hysterectomy (LARVH), which is associated with the laparoscopical procedure, and it is applied as radical vaginal trachelectomy and semi-radical vaginal hysterectomy. LARVH is indicated for patients with stage IB1 and IIA1 cervical carcinoma, especially those with a tumor size of less than 2 cm, because the cardinal ligaments cannot be resected widely. Although RVH that is associated with laparoscopic pelvic lymphadenectomy is the most used surgical procedure, radical trachelectomy may be performed either abdominally or vaginally (laparoscopic or robotic). One report found that the pregnancy rate was higher in patients who underwent minimally invasive or radical vaginal trachelectomy than in those who underwent radical abdominal trachelectomy.

ERα increases endometrial cancer cell resistance to cisplatin via upregulation of BAG3.

Endometrial cancer is a leading cause of cancer-associated mortality in women and has a poor prognosis in advanced stages. Our previous study revealed that BCL-2-associated athanogene 3 (BAG3) may contribute to enhancing cell viability through downregulation of microRNA (miR)-29b in endometrial cancer cell lines. In addition, a relationship between estrogen receptor α (ERα) and BAG3 was recently reported in several cancer cell types. The present study investigated the relationship between ERα and BAG3 in endometrial cancer cell lines. The results demonstrated that exogenous ERα overexpression enhanced BAG3 expression in the EMTOKA endometrial cancer cell line, which does not endogenously express ERα, but had no effect on BAG3 expression levels in the Ishikawa cell line, which does endogenously express ERα. In addition, ERα overexpression suppressed miR-29b expression and enhanced the expression of Mcl-1, a mediator situated downstream of BAG3, in EMTOKA cells, but not Ishikawa cells. ERα overexpression also enhanced EMTOKA, but not Ishikawa, endometrial cancer cell viability in the presence of cisplatin. These findings suggested that ERα may contribute to enhancing endometrial cancer cell resistance to anticancer agents through BAG3 overexpression.

Mucinous carcinoma originating in the peritoneum diagnosed by an ascites cell block: a case report.

BACKGROUND: Peritoneal carcinoma is a rare disease that is diagnosed and treated in a manner similar to ovarian cancer. In most cases, the histological type is serous carcinoma, and chemotherapy is effective. However, there are a few case reports of mucinous peritoneal carcinoma. We inferred the histological type before surgery using an ascites cell block sample, which was useful for determining the treatment plan. CASE PRESENTATION: Our patient was a 60-year-old Japanese woman. She presented with a feeling of fullness in the abdomen. A computed tomographic scan showed a large quantity of ascitic fluid and thickening of the greater omentum, as well as thickening of the peritoneum at the pouch of Douglas and diaphragm. Hence, peritoneal carcinoma was suspected. The tumor markers carcinoembryonic antigen, cancer antigen 19-9, and cancer antigen 125 were all increased, and no malignant findings were observed in the uterus or ovaries. Cells suggestive of carcinoma were found in the ascitic fluid, and immunostaining by the cell block method suggested the possibility of mucinous carcinoma. The preoperative chemotherapy strategy was changed to short courses, and tumor reduction surgery was planned. Similar to the suspicion before surgery, the pathology results indicated mucinous carcinoma, and the therapeutic effect of chemotherapy was grade 0. CONCLUSIONS: Determining whether peritoneal carcinoma is serous carcinoma is important for therapy and prognostic prediction. In this case, we encountered a patient for whom surgery was chosen because of drug therapy resistance inferred through histological type estimation using the cell block method. Inferring the histological type by cell block preparation is useful for diagnosis and treatment selection.

Three-Dimensional Peripheral Bloodstream Model of the Uterus for Laparoscopic Radical Hysterectomy.

Trainees require extensive experience to perform radical hysterectomy. Before starting training during an actual operation, trainees should be familiar with the pelvic anatomy and should simulate surgical procedures. Many simulators are available for virtual reality training of laparoscopic operations, but they are very expensive. The materials required to construct our model included sponges and colored wires sold in home improvement stores that allowed for superior cost effectiveness. The model represented almost all peripheral vessels and nerves around the uterus, including the minor vessels. Attaching and detaching the vessels was easy, facilitating reconstruction of the dissected vessels. The wires were easy to bend, ensuring high operability. This model allows for the simulation of laparoscopic radical hysterectomy in a dry box. Our model was superior to a 2-dimensional picture for the memorization of branching and positional relationships of the blood vessels. Comparison of our model with actual operative videos showed that the dry box provided an identical surgical view of an actual laparoscopic radical hysterectomy. We developed a peripheral bloodstream model of the uterus for repeated simulation of laparoscopic radical hysterectomy with an actual surgical view using a dry box.

Efficacy of liquid-based genetic diagnosis of endometrial cancer.

Although liquid-based cytology (LBC) has increased the sensitivity of cytological diagnosis of endometrial cancer (EC) compared with conventional smear cytology, the sensitivity of LBC for the detection of EC is between 70% and 96% and remains unsatisfactory. In the present study, we compared the efficacy of LBC with liquid-based genetic diagnosis (LBGDx) by amplicon sequencing of five genes including PTEN, PIK3CA, CTNNB1, KRAS, and TP53 in 48 LBC subjects who underwent endometrial screening. Consequently, LBC classified 15 samples as "positive or suspicious for malignancy" and the 15 were later confirmed as EC. However, LBC failed to identify five cases who were diagnosed as EC by additional transvaginal ultrasound and endometrial curettage, indicating that the sensitivity of cytology alone was 75% (15/20). LBGDx identified 11 pathogenic PTEN variants in 10 subjects, six PIK3CA variants in nine, three CTNNB1 variants in five, two KRAS variants in four, and three TP53 variants in three. Collectively, at least one pathogenic variant was identified in 19 subjects, which included 17 EC (15 endometrioid carcinoma and 2 endometrial carcinosarcomas), and one cervical adenocarcinoma. However, LBGDx did not identify any pathogenic mutations in three of the 20 EC, indicating that the sensitivity of LBGDx alone was 85% (17/20). Although five EC were negative for malignancy by LBC and three were negative for pathogenic mutations by LBGDx, the combination of LBC and LBGDx would successfully diagnose all 20 EC. These data suggested that LBGDx is a useful strategy to improve the sensitivity of screening of EC by LBC.

Rap1GAP inhibits tumor progression in endometrial cancer.

OBJECTIVE: Endometrioid adenocarcinoma (EAC) is a common endometrial cancer with recent dramatic increases in incidence. Previous findings indicate that Rap1GAP acts as a tumor suppressor inhibiting Ras superfamily protein Rap1 in multiple aggressive carcinomas; however, Rap1GAP expression in EAC has not been investigated. In this study, the tumor suppressing activity of Rap1GAP in EAC was explored. METHODS: EAC cell lines were used to examine Rap1GAP levels by real-time RT-PCR and western blotting and the effects of Rap1GAP on cancer cell invasion and migration. Rap1GAP expression was analyzed by immunohistochemical staining for Rap1GAP, E-cadherin in surgically resected tumors of 114 EAC patients scored according to EAC differentiation grade. Prognostic variables such as age, stage, grade, tumor size, and immunostaining for Rap1GAP, E-cadherin were evaluated using Cox regression multivariate analysis. RESULTS: Low Rap1GAP expression was detected in poorly differentiated EAC cells. Rap1GAP deficiency significantly accelerated while Rap1 deficiency decreased cancer cell migration and invasion. Patients with higher Rap1GAP, E-cadherin, and especially combined Rap1GAP/E-cadherin levels had better overall survival than EAC patients with no or weak expression. In addition, Rap1GAP expression was an independent prognostic factor in EAC. CONCLUSIONS: Inhibition of Rap1GAP expression increases EAC cell migration and invasion through upregulation of Rap1. Low expression of Rap1GAP correlates with poor EAC differentiation. Our findings suggest that Rap1GAP is an important tumor suppressor with high prognostic value in EAC.