Pseudomyxoma peritonei (PMP), which involves both the ovaries and appendix, is usually attributed to an appendiceal primary tumor with secondary involvement. However, rare cases may present with synchronous, independent mucinous primaries. Distinguishing between these entities is important because staging, treatment, prognosis, and follow-up may differ according to the primary site. An 83-year-old woman presented with abdominal distension and ascites incidentally discovered during an evaluation for traumatic intracranial hemorrhage. Computed tomography revealed large-volume ascites, a large multilocular cystic mass arising from the left ovary, and a dilated appendix. Diagnostic laparoscopy confirmed the presence of gelatinous ascites, which was consistent with PMP. Histopathological examination revealed ovarian mucinous carcinoma and appendiceal mucinous neoplasms. Immunohistochemistry showed discordant profiles for ovarian (cytokeratin [CK]-7+/paired box 8 [PAX8]+/CK-20-/caudal-type homeobox 2 [CDX-2]-) and appendiceal (CK-20+/CDX-2+/CK-7-/PAX8-) lesions. Peritoneal tumor cells expressed CK-7 but lacked PAX8, CK-20, and CDX-2 expression, supporting an ovarian-type immunophenotype of the peritoneal disease. The patient underwent diagnostic laparoscopy with left salpingo-oophorectomy and removal of the gelatinous ascites. Two cycles of paclitaxel and carboplatin were administered before interval cytoreductive surgery because of advanced disease, arrhythmia, and poor tolerance to prolonged surgery. Complete cytoreduction was achieved through total hysterectomy, right salpingo-oophorectomy, appendectomy, total parietal peritonectomy, omentectomy, cholecystectomy, splenectomy, and the removal of visible disease, followed by carboplatin monotherapy. Complete cytoreduction was achieved, and the patient completed adjuvant carboplatin therapy without grade 3 or higher adverse effects. The patient remained disease-free for 6 months after the completion of chemotherapy.

The tumor suppressor p53 plays a crucial role in preventing cancer development, and its dysfunction is frequently observed in various cancers. This study identifies a novel regulatory interaction between p53 and ITM2A. We found that p53 upregulates ITM2A expression, while ITM2A in turn inhibits p53 function, suggesting a negative feedback loop. ITM2A mRNA levels were reduced across multiple tumor types, particularly in those harboring mutant p53, and low ITM2A expression correlated with poor patient survival. Mechanistically, ITM2A physically interacts with p53, selectively modulates its phosphorylation (reducing Ser392 while enhancing Ser37), and promotes cytoplasmic accumulation of p53. These modifications collectively suppress p53-dependent transcription, an effect consistently observed across multiple cell lines under both basal conditions and upon physiological p53 activation by genotoxic stress. Conversely, ITM2A depletion enhances p53 nuclear accumulation and transcriptional activity. These findings reveal a novel autoregulatory circuit wherein p53 induces ITM2A expression, which then attenuates p53 activity, suggesting ITM2A as a potential prognostic marker and therapeutic target for cancers with dysregulated p53 signaling.

To evaluate the analgesic efficacy and opioid-sparing effect of two different doses of nefopam combined with oxycodone in intravenous patient-controlled analgesia (IV PCA) compared with oxycodone alone after laparoscopic abdominal surgery. In this single-center, randomized, single-blind, non-inferiority trial, 246 patients undergoing elective laparoscopic gastrointestinal or colorectal surgery were randomly assigned (1:1:1) to Group A (oxycodone 160 mg + nefopam 120 mg), Group B (oxycodone 130 mg + nefopam 200 mg), or Group C (oxycodone 200 mg, control), each in a 200 mL PCA bag. The primary endpoint was visual analogue scale (VAS) pain score at rest at 24 h postoperatively, with a non-inferiority margin of 1.0. Secondary endpoints included cumulative oxycodone consumption, rescue medication use, quality of recovery, and adverse events. A total of 230 patients were included in the intention-to-treat analysis. Both nefopam-oxycodone combinations were non-inferior to oxycodone monotherapy for the primary endpoint (mean difference, Group A vs. C: -0.33, 95% CI - 0.81 to 0.15; Group B vs. C: 0.00, 95% CI - 0.50 to 0.51). Cumulative oxycodone consumption at 96 h was reduced by 26.2% in Group A and 46.7% in Group B compared with the control group (both P < 0.001). The incidences of any adverse event, sedation, and respiratory depression did not differ among the three groups. In this single-blind trial, adding nefopam to oxycodone-based IV PCA provided non-inferior analgesia while substantially reducing opioid consumption after laparoscopic abdominal surgery. These results require confirmation in a double-blind trial with a fixed-opioid-dose design.Trial Registration: This study was registered at the Clinical Research Information Service of the Korean National Institute of Health (CRIS, http//cris.nih.go.kr), with registration number KCT0003896.

Patient-derived organoids (PDOs) can recapitulate selected features of original tumors and provide a useful system for studying epithelial ovarian cancer (EOC) in three-dimensional culture. Nonetheless, the protocol to generate EOC-PDOs has not yet been standardized. We therefore empirically refined the culture conditions and medium composition, considering the protocol effective when EOC PDOs were successfully established in five consecutive attempts. Tissue and ascites samples (from 29 and 8 patients, respectively) were used and the Syringe-extruded Organoid Basement membrane extract Assembly (SOBA) fragment culture method applied. Selected similarities in cell morphology, marker expression, and detectable alterations between organoids and patient-matched tumor tissue were assessed using pairwise comparisons. The refined workflow used a culture medium containing recombinant human R-Spondin 1 protein (250 ng/mL), Noggin, and NRG1, factors implicated in organoid maintenance and expansion. Ultimately, 31 EOC organoid lines successfully generated from 82.8% (24/29) of tissue and 87.5% (7/8) of ascites samples. The SOBA technique increased the 10 day PDO yield by 2.75-fold relative to the surface-attached dome method (p < 0.0001). This empirically refined workflow can be adjusted for specific experimental applications; however, further validation across larger and clinically diverse EOC cohorts is required.

Background/Objectives: The effects of combining chemotherapy with hormonal therapy based on hormone receptor (HR) expression in epithelial ovarian, fallopian tube, or primary peritoneal (EOC) remain unclear. This study evaluated the efficacy and safety of physician-chosen chemotherapy combined with hormonal therapy in patients with heavily pretreated advanced EOC, stratified by HR expression. Methods: This phase II, multicenter, pilot study included patients with heavily pretreated advanced EOC, allocated to estrogen receptor (ER)-dominant or progesterone receptor (PR)-dominant arms. Patients in the ER-dominant arm received tamoxifen plus physician-selected chemotherapy, while those in the PR-dominant arm received megestrol acetate (MA) plus chemotherapy. The primary outcome was the best objective response rate (ORR) for six months, assessed using an optimal two-stage Simon design. Results: Among 33 ER-dominant patients with high-grade serous carcinoma (HGSC), the six-month best ORR was 27.3% (3% complete response, 24.2% partial response). The six-month ORR and clinical benefit rate (CBR) were 18.8% and 37.5%, respectively, with 62.5% experiencing progressive disease (PD). Among three PR-dominant patients (two clear cell carcinoma and one HGSC), the six-month best ORR was 0%. The six-month ORR and CBR were also 0%, and all experienced PD within six months. No unacceptable toxicity related to tamoxifen or MA was encountered. Conclusions: In heavily pretreated advanced HGSC patients with ER-dominant expression, chemotherapy combined with tamoxifen showed encouraging clinical activity with favorable safety. While limited by the study design, these findings suggest a potential role for tailored hormonal therapy combined with chemotherapy based on HR expression in heavily pretreated advanced EOC. Clinical Trial Registration: KCT0004571

Approximately 100,000 human endogenous retroviruses (HERV) are integrated into the human genome. Most HERVs are not expressed; however, transcription within the family HERV-K, a class II beta-retrovirus, occurs in specific cancers. Herein, we investigated HERV-K env protein expression and its clinical and molecular significance in serous ovarian cancer. Protein expression was assessed via immunohistochemistry and QuPath digital analysis in 24 normal, 10 benign, 13 borderline and 72 cancerous serous ovarian tissues. Clinicopathological parameters were obtained from medical records. Transcriptomes were evaluated using strand-specific reverse transcription-PCR and sequencing. Antiproliferative activities were explored using MTT and colony formation assays. A stable transfection expression system and siRNA gene silencing were used. Resistant cell lines were established using the paclitaxel concentration gradient method and chemoresponsiveness was evaluated by measuring the IC50. HERV-K env was absent in normal ovarian epithelia and benign tumors but was detected in 37.5

Recent advancements in ovarian cancer treatment, particularly with PARP inhibitors, have markedly enhanced the recurrence-free interval, shifting the treatment paradigm and increasing treatment success in patients with BRCA mutations or HRD (homologous recombination deficiency). However, a significant proportion of cases experience relapse, resulting in poorer long-term survival rates when compared to other female cancers, such as breast cancer. This review explores the potential of adeno-associated virus (AAV) vectors for gene therapy in ovarian cancer and examines rational gene therapy strategies by categorizing them based on target cells and target genes to determine the most effective approach for ovarian cancer treatment. Specifically, it examines strategies such as anti-angiogenesis and immune modulation, highlighting the strategy of gene supplementation to hinder ovarian cancer progression. Innovations in AAV capsid design now allow for targeted delivery, focusing on ovarian cancer stem cells (CSCs) identified by specific markers. Additionally, leveraging DNA sequencing technologies enhances the identification and incorporation of therapeutic genes into AAV vectors, promising new avenues for ovarian cancer gene therapy.

The Korean Gynecologic Oncology Group (KGOG) was established in 2002 and is the only organization in Korea conducting multi-center clinical trials for gynecologic cancers. Since its re-establishment as a non-profit organization in 2021, KGOG has grown significantly, now including 207 gynecologic oncology specialists from 76 hospitals. This growth is a testament to the dedication and hard work of all those involved in the organization. KGOG is committed to maximizing the activation of multi-center clinical research through policies that support patients with rare diseases and gynecologic cancer research, focusing on strengthening institutional capacity, equalizing participation opportunities, and enhancing information sharing. A significant milestone for KGOG was becoming a member of the US Gynecologic Oncology Group (GOG) in 2005, allowing participation in GOG clinical trials. KGOG later joined the Gynecologic Cancer InterGroup (GCIG) and strengthened its capabilities by hosting the first Endometrial Cancer Consensus Conference—Clinical Research (ECCC-CR) in 2023. KGOG holds biannual meetings and symposia, as well as 224 operating committee meetings annually to review the discussions of the Tumor Site Committee. KGOG has conducted 156 investigator-initiated trial (IIT) or sponsor-initiated trial (SIT) studies as KGOG-led or participated in research. Currently, 18 studies are registered, and 10 are in preparation. To date, 68 papers have been published. KGOG conducts six national projects and collaborates with external organizations such as the NRG Oncology Foundation, Gynecologic Oncology Group Partners (GOG-P), GCIG, East Asian Gynecologic Oncology Trial group (EAGOT), and the Japanese Gynecologic Oncology Group (JGOG). Through collaboration with renowned international research institutions, KGOG has significantly expanded the scope of its research, achieving noteworthy clinical outcomes. This report not only introduces the history and recent status of KGOG but also presents the exciting future direction of the organization, filled with potential breakthroughs and advancements in gynecologic oncology research.

Objective: Because of the possible therapeutic benefit of removing occult tumor cells, a source of recurrence and chemoresistance, total parietal peritonectomy (TPP) is an alternative treatment for advanced epithelial ovarian/fallopian tube/primary peritoneal cancer. Interventional studies comparing TPP with selective parietal peritonectomy (SPP) are in progress. Since surgeons skilled in TPP are essential for such trials to be conducted, this nationwide survey aimed to examine current peritonectomy practice among gynecologic oncologists in Korea. Methods: A 17-item questionnaire, developed by a surgery committee and reviewed by the scientific review board of the Korean Gynecology Oncology Group (KGOG), was distributed to 144 KGOG members. The questionnaire was divided into 3 categories: respondent demographics, peritonectomy practice during primary debulking surgery (PDS), and peritonectomy practice during interval debulking surgery (IDS). Results: We received 88 (61.1%) valid responses. Of the valid respondents, 98.9% and 93.8% performed SPP during PDS and IDS, respectively. Only 4.9% of the respondents performed TPP during IDS. Most respondents performed peritonectomy in cases where optimal postoperative outcomes were expected. Approximately 50.6% of the respondents had performed peritonectomy independently, while the others did so in cooperation with non-gynecologic surgeons. The primary reasons for not performing TPP were concerns about morbidity and uncertainty about the clinical benefits of the procedure. Conclusion: SPP is the predominant technique used in both PDS and IDS in Korea. A small percentage (4.9%) of gynecologic oncologists have performed TPP during IDS. Accordingly, a study regarding the feasibility of TPP should be conducted before proceeding with a prospective clinical trial.

Intra-abdominal adhesion is a complication following abdominal surgery caused by the suppression of fibrinolytic activity and aggravated fibroblast invasion of the injured area, which may lead to chronic illnesses such as chronic pain, intestinal obstruction, and female infertility. This study hypothesized that lumbrokinase, a fibrinolytic enzyme extracted from the earthworm, supports the wound healing process. Therefore, we assessed the effect of lumbrokinase on intra-abdominal adhesion. Lumbrokinase treatment significantly decreased the severity and the area of intra-abdominal adhesion in vivo in a dose-dependent manner compared with the controls (untreated and hyaluronate-treated). Lumbrokinase-associated adverse effects were not observed. Immunohistochemical analysis of adhesion tissues revealed a loosened adhesive band between tissues, coupled with significantly decreased peritoneal thickening in the lumbrokinase-treated group versus the control group. Three-dimensional spheroid, MTT, and scratch wound migration assays using the IMR-90 human fibroblast cell line demonstrated that lumbrokinase significantly attenuated the migration and adhesive activity of fibroblasts without compromising cell proliferation. The luciferase assay and western blot analysis showed that lumbrokinase inhibited the AP-1/ICAM-1 cell adhesion signaling pathway. Therefore, lumbrokinase decreases intra-abdominal adhesion and peritoneal thickening by augmenting fibrinolytic action and inhibiting fibroblast migration and adhesive activity via attenuation of the AP-1/ICAM-1 signaling pathway. Lumbrokinase is thus a promising agent to prevent intra-abdominal adhesion.

Surgical site infection (SSI) is associated with substantial morbidity. However, the incidence and clinical significance of SSIs after cytoreductive surgery in Korean females with epithelial ovarian, fallopian tube and peritoneal cancer (EOFPC) are unknown. We aimed to assess the incidence and consequences of SSI within 30 days after cytoreductive surgery in patients with EOFPC. After estimating the effect size, SSIs were retrospectively investigated in 149 patients between 2011 and 2020. Survival and multivariate analyses were performed using Kaplan-Meier estimates and the Cox regression method that included the interaction terms, respectively. Clinical factors for patients with or without SSI were compared using the Mann-Whitney U test and Fisher's exact test. The overall rate of SSI was 9.4% (14 of 149 patients), consisting of five superficial, three deep and six organ/space SSIs. No clinical significance of SSI was observed when analyzing the 149 cases. Among the 91 patients with FIGO stage III-IV serous type carcinomas, eight experienced SSI, and their clinical factors were compared with those of the 83 patients without SSI. A univariate analysis showed that patient age, neoadjuvant chemotherapy, suboptimal debulking status, FIGO stage, chemoresistance, a longer interval from surgery to initiation of chemotherapy (ISIC), and SSI occurrence were significantly associated with overall survival. The multivariate analysis showed that higher FIGO stage (HR 21.138; 95% CI 2.796-159.819; p = 0.003) and SSI occurrence (HR 21.999; 95% CI 2.616-184.986; p = 0.004) were independent predictors for poor overall survival. The SSI group had a significantly greater body mass index (p = 0.006) and a longer ISIC (23 +/- 9.1 vs. 40.0 +/- 25.7 days; p = 0.006) compared with the non-SSI group. In conclusion, SSI after cytoreductive surgery in patients with FIGO stage III-IV serous type carcinoma significantly worsened patient prognosis and delayed initiation of adjuvant chemotherapy.

Over the past few decades, research on life in space has increased. Owing to the expensive nature of and the challenges associated with conducting experiments in real space, clinostats, which continuously randomize the gravity vector by using motors, have been used to generate simulated microgravity (SMG) on Earth. Herein, by using a 3D printing method, we develop a customized small-sized clinostat (CS clinostat) that is easy to manufacture, inexpensive, and robust. Moreover, we develop and fabricate a gas-permeable polydimethylsiloxane culture dish that fits inside the CS clinostat. To validate SMG generation, ovarian cancer cells (OV- 90, TOV-21G, and Caov-3) were applied to demonstrate a significant reduction in caveolin-1 expression, a biomarker of SMG, indicating SMG generation. The proposed CS clinostat system has good accessibility for SMG research, which makes it useful as a tool for biologists, who are unfamiliar with conventional clinostat equipment, to conduct preliminary studies in the space environment.

Background The intra-abdominal cavity, surrounded by adipocytes, is the main metastatic site of epithelial ovarian, fallopian tube, and peritoneal cancer. Epidemiological and molecular studies have demonstrated a link between adipose tissue and ovarian cancer. However, the clinical significance of fatty tissue has not been elucidated. Thus, we investigated the clinical significance of body composition in patients with epithelial ovarian, fallopian tube, and peritoneal cancer. Methods Fat and skeletal muscle areas were measured using software based on pretreatment computed tomography scans at the third lumbar vertebra. Fat-to-muscle ratios were calculated using the total (visceral and subcutaneous) fat area or visceral fat area. High fat-to-muscle ratios were defined by values greater than the mean. Sarcopenia was defined as a skeletal muscle index < 38.7 cm 2 /m 2 . The clinicopathological parameters and survival of 153 patients were analyzed. Results High visceral fat-to-muscle ratios and sarcopenia at the time of diagnosis were observed in 43.8% and 33.3% of the patients, respectively. Multivariate analysis showed that high visceral fat-to-muscle ratio ( p = 0.014), advanced Federation of Gynecology and Obstetrics stage ( p = 0.008), and chemoresistance ( p = 0.027) were independent factors for worse overall survival. Patients with high visceral fat-to-muscle ratios were older, had higher body mass indexes, and were more likely to have diabetes/hypertension, serous cancer subtypes, and implementation of neoadjuvant chemotherapy than those with low visceral fat-to-muscle ratios. The platelet count was significantly higher in the high visceral fat-to-muscle ratio group than in the low visceral fat-to-muscle ratio group ( p = 0.011). Conclusions Pretreatment visceral fat area could be an independent predictive factor of overall survival in patients with epithelial ovarian, fallopian tube, and peritoneal cancer and may be significantly associated with thrombocytosis.

Introduction Radiotherapy is preferred in the cases if lymph node involvement is detected before surgery. However, radiotherapy with standard dose is insufficient to sterilize bulky lymph nodes > 2 cm. The resection of bulky lymph node metastasis before radiotherapy has been proposed to provide a therapeutic benefit. Description A sixty-four-year-old woman had been diagnosed of cervical adenocarcinoma with a biopsy. Gynecological examination and computed tomography detected both parametrial involvement and metastatic nodes about 3.3 cm and 2.1 cm in size at bilateral obturator fossa. Concurrent chemoradiation therapy was planned after the removal of the bulky nodes. A two-trocar transperitoneal approach with accessary port for assistant was used. After establishing retroperitoneal space, the ureter was retracted medially. Right node that was 3.3 cm in size was between the external iliac vein and internal iliac artery and extended to the obturator fossa. The operation was followed by the left pelvic node removal. The robotic-assisted operation time was 124 minutes and the hospital stay was four days. The patient received concurrent chemoradiation therapy and had well been for one year with no evidence of disease. Conclusion/Implications The bulky lymph nodes which were difficult to be eradicated with standard radiation therapy were successfully resected with robotic-assisted surgery. The removal of bulky nodes followed by radiation therapy may provide a therapeutic benefit.

Robotic surgery has advantages in myomectomies, which are a technically complex surgery. Multi-site robotic myomectomy (MRM) is widely used and is a safe, minimally invasive surgery. Single-site robotic myomectomy (SSRM) is further expected to provide potential advantages such as better cosmesis and easier fibroid removal. Compared with MRM, SSRM has technical limitations, including a restricted range of motion, especially for large-sized myomas; less powerful suturing in thick myometrium; and non-articulating instruments. To overcome these limitations, additional ports are used, larger skin incisions are made, and the procedure is combined with laparoscopy. However, these adjustments may neutralize the advantages of a single-port surgery. Here we describe our novel gradual turning out method, which enables us to do SSRM without adjustments. Additionally, we introduce know-how on how to accomplish an SSRM.

6-Azauridine (6-AZA), a pyrimidine nucleoside analogue, is known to exhibit both antitumor and antiviral activities. Although 6-AZA was discovered more than 60 years ago, the cellular effects of this compound are yet to be elucidated. Here, we report that 6-AZA regulates autophagy-mediated cell death in various human cancer cells, where 6-AZA treatment activates autophagic flux through the activation of lysosomal function. Furthermore, 6-AZA exhibited cytotoxicity in all cancer cells studied, although the mechanisms of action were diverse. In H460 cells, 6-AZA treatment induced apoptosis, and the extent of the latter could be reduced by treatment with chloroquine (CQ), a lysosomal inhibitor. However, 6-AZA treatment resulted in cell cycle arrest in H1299 cells, which could not be reversed by CQ. The cytotoxicity associated with 6-AZA treatment could be linearly correlated to the degree of autophagy-mediated cell death. In addition, we demonstrated that the cytotoxic effect of 6-AZA was dependent on AMPK and p53. These results collectively indicate that autophagy-mediated cell death triggered by 6-AZA contributes to its antitumor effect.

Background Endometrial cancer is often the sentinel cancer in women with Lynch syndrome, among which endometrioid endometrial cancer is the most common. We found a Korean case of uterine carcinosarcoma associated with Lynch syndrome. And we reviewed 27 Korean women with endometrial cancer associated with Lynch syndrome already released in case report so far. Case presentation The proband, a 45-year-old Korean woman received treatment for endometrioid adenocarcinoma. Her older sister and niece were treated for endometrioid adenocarcinoma and carcinosarcoma, respectively. Family history met the Amsterdam II criteria and immunohistochemical analysis revealed a loss of MLH1 and PMS2 . They all harbored a previously unreported germline likely pathogenic variant in c.1367delC in MLH1 . They underwent staging operations including total hysterectomy, bilateral salpingo-oophorectomy, pelvic/paraaortic lymph node dissection, and washing cytology. All three women were healthy without evidence of relapse for over 4 years. Conclusion This report indicates a novel germline c.1367delC variant in MLH1 , and presents a Korean case of uterine carcinosarcoma associated with Lynch syndrome. Furthermore, the c.1757_1758insC variant in MLH1 was suggested as a founder mutation in Lynch syndrome in Korean women.

Endometriosis is one of the most common diseases in reproductive ages, and it affects patients' quality of life and fertility. However, few Korean guidelines are available for the evaluation and management of endometriosis. Korean Society of Endometriosis reviewed various literatures and trials, and to provide seventy-one evidence-based recommendations. This review presents guidelines for the diagnosis and management of endometriosis with emphasis on: it's role in infertility, treatment of recurrence, asymptomatic women, endometriosis in adolescents and menopausal women, and possible association of endometriosis with cancer.

Endometriosis is a major cause of disability in women, and 40% to 50% of patients experience disease recurrence by 5 years after surgery. This multicenter retrospective cohort study (N = 588) determined the rate and risk factors for recurrent endometrioma after primary surgery and examined the role of postoperative hormone therapy. When recurrence was defined by sonographic identification of the endometrioma (≥20 mm in size), 61 (10.4%) patients experienced disease recurrence. The cumulative recurrence rates at 1, 2, 3, and 5 years after surgery were 2.2%, 4.9%, 6.9%, and 9.8%, respectively. To determine the risk factors for recurrence, the clinical factors of patients with and without recurrence were compared. There was a significantly increased risk of recurrence with posterior cul-de-sac (PCDS) obliteration (P = .031) and higher serum cancer antigen 125 (CA125) level (P = .005). A longer postoperative hormonal therapy duration (P < .01), absence of PCDS obliteration (P = .036), and lower serum CA125 level (P = .014) were associated with longer recurrence-free interval on multivariate analysis using the Cox regression model. Postoperative hormone therapy prolonged the interval from the time of surgery to the first recurrence. However, it did not prolong the interval from the end of treatment to the first recurrence. Our results indicate that although long-term postoperative hormone therapy might maintain minimal disease status, it does not control residual disease. Therefore, persistent hormone suppression should be used to prevent disease recurrence.