Surgical training in extraperitoneal laparoscopic para­aortic lymphadenectomy for the treatment of gynecological cancer using a Thiel­embalmed cadaver.

The extraperitoneal laparoscopic approach (ELPAN) for para-aortic lymphadenectomy provides excellent visibility of the left side of the aorta, thus facilitating surgery in the retroperitoneal space. This technique is highly complex compared with the transperitoneal approach. In particular, advanced techniques are required to develop an appropriate surgical field in the narrow retroperitoneal space; therefore, surgeons need to undergo a significant amount of training to become competent. A variety of tools are available for surgical training but are limited by their ability to reproduce complex anatomy. Thus, cadavers may represent the most suitable tool for learning this unique technique. The present study describes a surgical training protocol for the ELPAN technique using a Thiel-embalmed human cadaver and provides a step-by-step description of the ELPAN technique performed at Okayama University (Okayama, Japan). A 72-year-old Thiel-embalmed female cadaver was used to develop a protocol for surgical training in the ELPAN technique that effectively reproduced the methodology required in clinical practice. A training method for ELPAN surgery was developed and successfully completed using the Thiel-embalmed cadaver that secured the surgical field in the retroperitoneal space and permitted resection of the lymph nodes. The Thiel-embalmed cadaver tissue possessed excellent properties for surgical training, including color tone, flexibility, and the membrane structure of connective and fat tissues. In addition, this method of fixation preserved stiffness and elasticity of the peritoneum, although large vessels were slightly fragile and poorly extensible. Surgical training using a Thiel-embalmed human cadaver represents a valuable option for learning the ELPAN surgical technique. However, this technique may be unsuitable for training in perivenous manipulation. To the best of our knowledge, this is the first report to describe the use of Thiel-embalmed cadavers as a tool for surgeons to undergo training in the ELPAN technique.

Total laparoscopic wedge resection for an intramural ectopic pregnancy using an intraoperative ultrasound system: A case report.

Intramural pregnancy is a rare form of ectopic pregnancy, and the optimal treatment remains uncertain. We describe a 33-year-old woman (gravida 2, para 0) who visited our hospital with suspected ectopic pregnancy. The patient was asymptomatic and hemodynamically stable. Transvaginal ultrasonography revealed pregnancy at 6 weeks of gestation and a gestational sac and fetal heartbeat in the anterior muscular layer of the uterus, away from the endometrium. The fetal sac measured 26 mm. The serum human chorionic gonadotropin (hCG) level had increased to 27 655 mIU/mL. Accordingly, the patient was diagnosed with an intramural ectopic pregnancy and underwent total laparoscopic wedge resection using intraoperative ultrasonography. The postoperative course was uneventful, and she was discharged after 4 days. Her serum hCG level normalized at 26 days postoperatively. This case indicates that intraoperative laparoscopic ultrasonography seems viable for treating intramural pregnancies.

Adenosine Deaminase Family Acting on RNA 1 (ADAR1) May Be a De Novo Target for Endometriosis Treatment.

BACKGROUND/AIM: Adenosine deaminase family acting on RNA 1 (ADAR1) expression was examined to determine its correlation with endometriosis. The biological functions and inhibitory effects of ADAR1 knockdown were investigated in a human endometriotic cell line. MATERIALS AND METHODS: ADAR1 was examined in patients with and without endometriosis using reverse transcription polymerase chain reaction (RT-PCR), and the apoptotic expression of ADAR1 small interfering RNA (siRNA) was confirmed using flow cytometry. The biological functions and inhibitory effects of ADAR1 knockdown were investigated using RT-PCR in a 12Z immortalized human endometriotic cell line. RESULTS: ADAR1 expression was significantly higher in patients with endometriosis than in those without (p<0.001). ADAR1 siRNA increased early and late apoptosis, compared to the mock (24.83%) and control (19.96%) cells. ADAR1 knockdown led to apoptosis through MDA5, RIG-I, IRF3, IRF7, caspase 3, caspase 7, and caspase 8 expression in the cell lines. CONCLUSION: ADAR1 is a potential novel therapeutic target in endometriosis.

Assessing the efficacy of simulation-based education for paramedics in extended focused assessment with sonography for trauma under physician guidance.

We investigated the effectiveness of simulation-based education in Focused Assessment with Sonography for Trauma (FAST) to increase the number of Emergency Medical Technicians (EMTs) capable of performing ultrasound examinations in vehicles under the guidance of a physician. Twenty-eight paramedics watched a 14-min video on the features of the ultrasound system, its use, and the scanning method for each part of the body. Each participant performed four FAST examinations using a portable ultrasound device, and the task performance was rated using the Task Specific Checklist (TSC) and Global Rating Scale (GRS). The time required for visualizing each examination site and each FAST was assessed. The mean time required for the first and fourth FAST was 144.6 ± 52.4 s and 90.5 ± 31.0 s, respectively. The time required for each test significantly decreased with repeated testing (p < 0.001). The time to complete FAST was significantly shortened for the pericardial cavity (33.4 ± 23.1/15.3 ± 10.6 s, p < 0.01), right thoracic cavity (25.2 ± 11.8/12.1 ± 8.3 s, p < 0.01), Morrison fossa (19.1 ± 10.8/10.8 ± 6.3 s, p < 0.05), and left thoracic cavity (19.0 ± 8.3/15.6 ± 8.3 s, p < 0.05). TSC and GRS scores were elevated, and all EMTs could obtain valid images. The combination of a brief video lecture and hands-on training significantly reduced the time required for FAST performance. Moreover, repeated practice enabled the EMTs to efficiently obtain accurate and clinically useful images.

Association of Regular Cervical Cancer Screening with Socioeconomic, COVID-19 Infection and Vaccine Status Among Japanese Population: Cohort Observational Study.

Purpose: Among the Organisation for Economic Co-operation and Development countries, Japan has one of the lowest cervical cancer screening coverages. Cancer screening coverage has worsened due to the coronavirus disease of 2019 (COVID-19) pandemic. This study investigated the relationship between socioeconomic background, COVID-19 infection history and vaccine status, and regular cervical cancer screening (CCS) during the two years of the COVID-19 era in Japan. Patients and Methods: We used data from the Japan COVID-19 and Society Internet Survey, a nationwide, Internet-based, self-report cohort observational study conducted in 2022. The outcome variable was identified by asking whether the participants had undergone CCS within the last two years. Cervical cytology was performed in Japan by brushing the external cervical os. This study used multivariate log-binomial regression models to evaluate inequalities during regular checkups for CCS. Adjusted prevalence ratios (APRs) with 95% confidence intervals (CIs) were estimated to incorporate the socioeconomic background variables. Results: Of the 12,066 participants, 5597 (46.4%) had undergone regular CCS for over two years. The prevalence ratio (PR) of patients who underwent CCS was 0.70 for those in their 20s and 0.78 for those in their 60s, compared to those in their 40s. Socioeconomic inequities were found in the following groups: unemployed/student, unmarried, high school graduate or lower, and household income below 4 million Yen. Our final multivariate analysis revealed that participants who were in their 20s or 60s, had a household income below 4 million Yen, were unmarried, had no annual health check-ups, and were unvaccinated with COVID-19 were at a higher risk of not undergoing CCS. Conclusion: The relationship between socioeconomic inequality and CCS hesitancy is prevalent among younger participants. The CCS coverage in Japan during the COVID-19 pandemic year (2020-2022) was not low compared with the pre-pandemic era.

Investigation of optimal weight gain during pregnancy: A retrospective analysis of the Japanese perinatal registry database.

AIM: This study aimed to determine the weight gain during pregnancy that minimizes the predicted probability of various perinatal adverse events according to the pre-pregnancy body mass index (BMI) and make recommendations for optimal weight gain in Japan. METHODS: The Japan Society of Obstetrics and Gynecology perinatal database for 2015-2017 was used. From the 719 723 deliveries included in this database, parturients with underlying diseases or missing data were excluded, and 419 114 deliveries were analyzed. A questionnaire survey was also conducted to weigh each perinatal adverse event. For each of the nine outcomes, a restricted cubic spline model was made to estimate the association between the "expected gestational weight gain at 40 weeks" and the outcome risk. RESULTS: Since the classes of medical facilities were generally the same, weights were assigned according to the mean of the questionnaires rather than by the class of the facility. For each pre-pregnancy BMI, the weight gains during pregnancy that minimized the predicted probability of various adverse perinatal events were 12-15, 10-13, 7-10, and upper limit of 5 kg for the underweight, normal-weight, obese 1, and obese ≥2 groups, respectively. CONCLUSIONS: The weight gain during pregnancy that minimizes the predicted probability of various perinatal adverse events according to the pre-pregnancy BMI was established.

Not taking sick leave for gynecologic cancer treatment is negatively associated with returning to the same workplace.

BACKGROUND: Gynecologic cancers are one of the most common types of malignancies in working-age women. We aimed to determine the factors that impede women from returning to the same workplace after treatment for such cancers. METHODS: A questionnaire-based survey was conducted on 194 women who underwent treatment for gynecologic cancer at the Okayama University (≥1 year after cancer treatment and <65 years of age). We performed a logistic regression analysis to determine the relationship between returning to the same workplace and not taking sick leave. RESULTS: The median age at diagnosis was 49.0 years, and the median time from cancer treatment to questionnaire completion was 3.8 years. Not returning to the same workplace was positively associated with not being regularly employed (P = 0.018), short work time per day (P = 0.023), low personal income (P = 0.004), not taking sick leave (P < 0.001), advanced cancer stage (P = 0.018) and long treatment time (P = 0.032). Interestingly, not taking sick leave was strongly associated with not returning to the same workplace in the multivariable analysis (P < 0.001). CONCLUSIONS: Not taking sick leave likely was negatively associated with returning to the same workplace after the treatment for gynecologic cancer. Therefore, we suggest that steps be taken to formally introduce a sick leave system over and above the paid leave system in Japan.

Efficacy and safety of olaparib, olaparib plus bevacizumab and niraparib maintenance treatment in Japanese patients with platinum-sensitive advanced ovarian cancer.

OBJECTIVE: To investigate whether maintenance treatment could be safely and effectively performed with olaparib, olaparib plus bevacizumab and niraparib in platinum-sensitive advanced ovarian cancer at multiple institutions in Japan. METHODS: We investigated progression-free survival and adverse events in 117 patients with platinum-sensitive advanced ovarian cancer treated with maintenance therapy. RESULTS: The median progression-free survival of 117 patients was 20.1 months. Patients with germline BRCA pathogenic variants had a significantly better prognosis than the other groups (P < 0.001). Furthermore, in the multivariate analysis, stage IV (P = 0.016) and germline BRCA wild-type (P ≤ 0.001) were significantly associated with worse progression-free survival in patients with advanced ovarian cancer. Regarding adverse events, all three types of maintenance treatment were significantly worse than chemotherapy given before maintenance treatment with respect to renal function (olaparib, P = 0.037; olaparib plus bevacizumab, P < 0.001; and niraparib, P = 0.016). CONCLUSION: Maintenance treatment was performed effectively and safely. Renal function deterioration is likely to occur during maintenance treatment, and careful administration is important in platinum-sensitive advanced ovarian cancer.

Successful myomectomy using barbed sutures at 15 weeks of gestation: A case report.

To date, there are no reports on the use of barbed sutures in myomectomy during pregnancy. Herein, successful laparotomic myomectomy at 15 weeks of gestation using barbed sutures is described. A 38-year-old pregnant woman with a large myoma (16 × 11 cm) underwent myomectomy at 15 weeks and 4 days of gestation because of strong pain at the myoma site, a high level of inflammatory markers with degeneration of uterine fibroids, and severe anemia caused by denaturation of myoma. The uterine wall was reconstructed using monofilament absorbable 0 barbed sutures. Unlike conventional sutures, barbed sutures do not retract, so an assistant does not need to hold onto it during reconstruction of the uterine wall, resulting in less pressure and damage to the gravid uterus while maintaining resistance and the ability to hold the tissue under tension. The pregnancy continued with no evidence of myometrial thinning or symptoms of preterm labor. The patient delivered a healthy baby via cesarean section due to partial placenta previa at 36 weeks. The case shows the satisfactory outcome of perinatal myomectomy using barbed sutures during pregnancy.

Partner relationships, hopelessness, and health status strongly predict maternal well-being: an approach using light gradient boosting machine.

No recent study has explicitly focused on predicting the well-being of pregnant women. This study used data from an extensive online survey in Japan to examine the predictors of the subjective well-being of pregnant women. We developed and validated a light Gradient Boosting Machine (lightGBM) model using data from 400 pregnant women in 2020 to identify three factors that predict subjective well-being. The results confirmed that the model could predict subjective well-being in pregnant women with 84% accuracy. New variables that contributed significantly to this prediction were "partner help", "hopelessness," and "health status". A new lightGBM model was built with these three factors, trained and validated using data from 400 pregnant women in 2020, and predicted using data from 1791 pregnant women in 2021, with an accuracy of 88%. These factors were also significant risk factors for subjective well-being in the regression analysis adjusted for maternal age, region, parity, education level, and the presence of mental illness. Mediation analysis, with "hopelessness" as the mediator, showed that both "partner help" and "health status" directly and indirectly affected the outcome.

Relationship Between Hematological Toxicities During Maintenance Treatment and During Chemotherapy Before Maintenance Treatment in Patients With Platinum-sensitive Relapsed Ovarian Cancer.

BACKGROUND/AIM: To determine if maintenance treatment can be performed effectively and safely in patients with platinum-sensitive relapsed ovarian cancer. PATIENTS AND METHODS: We carried out a multi-center study to investigate progression-free survival (PFS) and adverse events (AEs) in 229 patients receiving maintenance treatment for platinum-sensitive relapsed ovarian cancer. RESULTS: The median PFS in the 229 patients with maintenance treatment was 14.0 months (95% confidence interval=10.3-17.6 months). The hematological toxicities included ≥grade 3 anemia in 33.2% of cases. Anemia during maintenance treatment was significantly more common than anemia during chemotherapy given before maintenance treatment (p<0.001). Anemia during chemotherapy prior to maintenance treatment significantly increased the risk of anemia during maintenance treatment, compared with other clinical features (p<0.001). CONCLUSION: Maintenance treatment can be performed safely and effectively in patients with platinum-sensitive relapsed ovarian cancer. Anemia during chemotherapy given before maintenance treatment significantly increased the risk of developing anemia during maintenance treatment in patients with platinum-sensitive relapsed ovarian cancer.

Endothelin-1 production via placental (pro)renin receptor in a mouse model of preeclampsia.

INTRODUCTION: Preeclampsia (PE) pathogenesis is explained by the two-stage disorder theory. However, mechanisms underlying hypertension and proteinuria in PE remain unclear. The role of (pro)renin receptor (PRR) in PE pathology has received special attention. We examined endothelin-1 (ET-1) production via placental PRR in a PE mouse model. METHODS: At 14.5 day-post-coitum (DPC), we performed a reduced uterine perfusion pressure (RUPP) operation, ligating the uterine arteriovenous vessels in female mice. We also infused these mice with a PRR inhibitor, decoy peptide in the handle region of prorenin (HRP) for mice (NH2-RIPLKKMPSV-COOH). At 18.5 DPC, blood, urine, and placenta were collected; fetus and placenta were weighed. We evaluated placental hypoxia using quantitative polymerase chain reaction (PCR), with hypoxia-inducible factor-1α (HIF-1α) as index. We also evaluated PRR, transforming growth factor-ß1 (TGF-ß1), and ET-1 expression in the placenta using quantitative PCR and western blotting. ET-1 concentration in blood plasma was assessed using enzyme-linked immunosorbent assay. RESULTS: Blood pressure and proteinuria significantly increased, and fetal and placental weights decreased in RUPP mice. HIF-1α, PRR, TGF-ß1, and ET-1 expressions considerably increased in RUPP mice placentas. ET-1 concentration in RUPP mice blood plasma was markedly increased. PRR inhibitor suppressed these changes. DISCUSSION: In PE model mice that underwent RUPP treatment, placental hypoxia increased PRR and ET-1 expression suggesting a causative relationship between ET-1 and intracellular PRR signaling. RUPP treatment, when combined with HRP, reversed the effect of elevated ET-1 levels in the model. This study may help to elucidate the pathogenesis of PE considering PRR and ET-1.

Pure abscopal effect in a patient with advanced uterine carcinosarcoma.

The abscopal effect is a rare phenomenon, in which tumor shrinkage in the nonirradiated metastatic region is observed after radiotherapy. Certainly, this response is sometimes reported with the combined use of immune-checkpoint inhibitors, but a pure abscopal effect is extremely rare, especially in endometrial cancer. We present the case of a 79-year-old woman with an advanced endometrial carcinosarcoma. She was treated with surgical reduction of the primary lesion, followed by radiotherapy of the metastatic regional lymph nodes. Distant metastases were detected in radiological imaging test 2 months after the completion of radiotherapy, and we carefully followed up without any treatment considering the patient's tolerability for further procedures. Six months after recurrence, she experienced cytoreduction in the metastatic lesions confirmed through imaging findings, which was believed to be an abscopal effect, and maintained this shrinking state for 15 months. Herein, we describe this pure abscopal effect from the perspective of imaging, pathological and molecular findings, and therapeutic strategies.

Short stature in small-for-gestational-age offspring born to mothers with hypertensive disorders of pregnancy.

OBJECTIVE: To investigate the incidence and risk factors of small-for-gestational age (SGA) short stature at 2 and 3 years of age in SGA offspring born to women with hypertensive disorders of pregnancy (HDP). METHODS: We examined 226 women with HDP whose respective SGA offspring were delivered. RESULTS: Eighty offspring (41.2%) were diagnosed with SGA short stature. The prematurity before 32 weeks of gestation was the most significant factor for catch-up growth failure. CONCLUSION: In SGA offspring born to women with HDP, SGA short stature incidence was high, and the risk factor was prematurity before 32 weeks of gestation.

ADAR1 has an oncogenic function and can be a prognostic factor in cervical cancer.

Adenosine deaminase acting on RNA 1 (ADAR1), a recently described epigenetic modifier, is believed to play a critical oncogenic role in human cancers. However, its functional role and clinical significance in cervical cancer (CC) remain unclear. ADAR1 knockdown was performed to investigate its oncogenic functions in SiHa (HPV16), HeLa (HPV18), and Yumoto (non-HPV) CC cell lines. Cytoplasmic and nuclear ADAR1 expression were examined to clarify their correlation with clinicopathological parameters and prognosis in patients with CC. This resulted in increased apoptosis and necroptosis in HPV16 -type SiHa, HPV18-type HeLa, and non-HPV-type Yumoto CC cell lines. Progression-free survival (PFS) rates of patients exhibiting high cytoplasmic and nuclear ADAR1 expression were poorer than those in the other groups (P = 0.016). Multivariate analysis indicated that the combination of higher cytoplasmic and nuclear ADAR1 expression was an independent predictor of prognosis in patients with CC (P = 0.017). ADAR1 could be a potential therapeutic target for HPV-positive or HPV-negative CC. The combination of cytoplasmic and nuclear ADAR1 comprises a better prognostic factor for CC.

Protocol for a randomised, placebo-controlled, double-blinded clinical trial on the effect of oestrogen replacement on physical performance to muscle resistance exercise for older women with osteoarthritis of knee joint: the EPOK trial.

BACKGROUND: Knee osteoarthritis (KOA) is highly prevalent in older women, and previous studies suggest the involvement of hormonal factors play a role in the pathogenesis of osteoarthritis. KOA causes musculoskeletal impairment, resulting in decreased physical activity, muscle mass, and strength, which leads to sarcopenia and further increases the burden on healthcare systems. Oestrogen replacement therapy (ERT) improves joint pain and muscle performance in early menopausal women. Muscle resistance exercise (MRE) is a non-pharmacological method that preserves the physical functions of patients with KOA. However, data on short-term oestrogen administration combined with MRE in postmenopausal women, especially in those aged > 65 years, are limited. Therefore, this study presents a protocol of a trial aimed to examine the synergistic effect of ERT and MRE on lower-limb physical performance in older women with KOA. METHODS: We will conduct a double-blinded, randomised placebo-controlled trial in 80 Japanese women aged > 65 years living independently with knee pain. The participants will be randomly categorised into two groups: (1) 12-week MRE programme with transdermal oestrogen gel containing 0.54 mg oestradiol per push and (2) 12-week MRE programme with placebo gel. The primary outcome measured using the 30-s chair stand test, and secondary outcomes (body composition, lower-limb muscle strength, physical performance, self-reported measure of knee pain, and quality of life) will be measured at baseline, 3 months, and 12 months, and these outcomes will be analysed based on the intention-to-treat. DISCUSSION: The EPOK trial is the first study to focus on the efficacy of ERT on MRE among women aged > 65 years with KOA. This trial will provide an effective MRE to prevent KOA-induced lower-limb muscle weakness, confirming the benefit of short-term oestrogen administration. TRIAL REGISTRATION: Japan Registry of Clinical Trials: jRCTs061210062. Registered 17th December 2021, https://jrct.niph.go.jp/en-latest-detail/jRCTs061210062 .

Therapeutic plasma exchange in postpartum HELLP syndrome: a case report.

BACKGROUND: Postpartum hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome is more difficult to treat than HELLP syndrome during pregnancy. We describe a case of postpartum HELLP syndrome that responded to plasma exchange (PE) therapy. CASE PRESENTATION: A 30-year-old primipara woman was hospitalized for gestational hypertension at 33 weeks of gestation and underwent an emergent cesarean section at 36 weeks and 6 days of gestation due to rapidly progressing pulmonary edema. After delivery, liver dysfunction and a rapid decrease in platelet count were observed, and the patient was diagnosed with severe HELLP syndrome. She experienced multiple organ failure despite intensive care, and PE therapy was initiated. Her general condition dramatically stabilized within a few hours of PE therapy. CONCLUSION: It is controversial whether PE therapy should be used primarily in the management of HELLP syndrome, but early initiation of PE therapy could be effective for severe HELLP syndrome.

Postpartum pyomyoma due to Mycoplasma hominis: A case report.

Pyomyoma is a rare condition that causes fever and abdominal pain associated with pregnancy, especially in the postpartum period. An appropriate diagnosis and early medical intervention are required to prevent serious complications. A 38-year-old primigravida with uterine fibroids had fever from the 11th day after cesarean section. The fever did not resolve despite repeated daily administration of broad-spectrum ß-lactam antibiotics for 2 weeks. Although the physical examination did not show any lower abdominal pain, a pelvic magnetic resonance scan revealed degenerative fibroids, and myomectomy was performed. Yellow-greenish odorless pus inside the uterus was detected, and Mycoplasma hominis was detected in the pus culture. Mycoplasma species are resistant to broad-spectrum penicillin antibiotics and can cause pyomyoma. Pyomyomas may not cause uterine tenderness, and the causative organism may be difficult to identify; therefore, additional imaging studies should be considered.

Liquid Biopsy Revealed HBOC Pedigree and Led to Medical Management Among the Relatives.

A hereditary breast and ovarian cancer (HBOC) pedigree was detected via liquid biopsy, and cancer prevention was initiated for the patient's daughter, after receiving a definitive result from BRCA genetic testing. A 48-yearold woman with ovarian cancer was administered precision medicine, which used cell-free DNA from plasma. The results revealed a pathogenic variant of BRCA1 as a presumed germline pathogenic mutation. We confirmed the germline pathological variant BRCA1 c.81-1G> A and suggested treatment with a PARP inhibitor. One of her three children had the variant, was diagnosed as an unaffected pathogenic variant carrier, and was advised to initiate surveillance.

Molecular Characteristics of Metastatic Lesions Have Superior Prognostic Impact on Endometrial Cancer.

BACKGROUND/AIM: In endometrial cancer (EC), lymph node (LN) metastasis significantly impacts prognosis. Thus far, no studies have reported the molecular genetics of each metastatic lesion. This study aimed to investigate the molecular characteristics of primary and metastatic LNs and their association with clinical outcomes. PATIENTS AND METHODS: The clinicopathological and molecular characteristics of 33 patients with EC with regional LN metastasis (FIGO stage IIIC) were investigated; we evaluated the mutational status of p53 and DNA mismatch repair (MMR) proteins in the primary lesion, all the positive LNs (102 lesions), mutational variation between primary and paired metastatic lesions, inter-lesion heterogeneity, and their association with clinical outcomes. RESULTS: Immunohistochemically, 12 patients (36.4%) displayed aberrant p53 expression in metastatic lesions, and a concordant rate of 93.4% was observed between primary and metastatic lesions. Inter-lesion heterogeneity was observed in 20 cases (60.6%). In Kaplan-Meier analysis, patients with aberrant p53 expression in metastatic LNs exhibited worse progression-free survival (PFS) than those with wild-type p53 expression (p=0.008). Wild-type p53 expression in primary lesion with inter-lesion heterogeneity had a significantly worse PFS (p=0.049) than those without heterogeneity. In the Cox univariate analysis, p53 expression in metastatic LNs was significantly associated with recurrence (p=0.013). Genetic diversity between primary and metastatic lesions and among metastases was validated by evaluating the p53 and MMR proteins using immunohistochemistry analysis. CONCLUSION: The molecular characteristics of metastatic lesions in addition to those of primary lesions could provide beneficial prognostic information in patients with EC with regional LN metastasis.