Predictive value of SUVmax from initial 18F-FDG PET/CT scans for treatment outcomes in endometrial cancer patients undergoing fertility sparing management.

OBJECTIVE: To evaluate whether the maximum standardized uptake value (SUVmax) from initial 18F-FDG PET/CT (fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography) scans could be a predictor of complete response and recurrence in patients with endometrial cancer who are undergoing fertility sparing management. METHODS: We conducted a retrospective review of patients who were diagnosed with endometrial cancer through biopsy and chose to undergo fertility sparing management using progestin at the Asan Medical Center, from January 2011 to December 2020. Of these, 113 patients who had an 18-FDG-PET/CT scan before starting treatment were included in our study. We measured SUVmax and examined its correlation with complete response and time to progression after achieving complete response to progestin therapy. RESULTS: Of 113 patients, 73 (64.6%) achieved a complete response through fertility sparing management. The receiver operating characteristic curve analysis revealed that the optimal cut-off value of SUVmax for predicting complete response was 6.2 (sensitivity 79.5%, specificity 57.5%, p=0.006). After analyzing recurrence in the 73 patients who achieved complete response, we found that patients with an SUVmax value >6.2 had a significantly shorter time to progression compared with those with a value <6.2. (p=0.04). CONCLUSIONS: SUVmax values of PET-CT, along with other clinicopathological parameters, could be used to predict treatment response and recurrence risk in patients with stage I endometrial cancer undergoing fertility sparing management.

Transcriptome profiling and characterization of peritoneal metastasis ovarian cancer xenografts in humanized mice.

Although immunotherapy has not yet been as successful in ovarian cancer (OC), it remains a potential therapeutic strategy. Preclinical models of OC are necessary to evaluate the efficacy of immuno-oncology (IO) drugs targeting human immune components but have been underutilized. Developing mouse models with a humanized (Hu) immune system can help understand the human immune response to IO drugs which have demonstrated limited effectiveness in OC patients. We established OC xenograft Hu-mouse models by intraperitoneally injecting luciferase-expressing SKOV-3 Luc and OVCAR-3 Luc OC cells into CD34+ Hu-mice. Tumor growth was monitored through bioluminescence imaging (BLI). In the SKOV-3 Luc Hu-mouse model, we assessed the efficacy of PD-1 blockade with pembrolizumab. We observed the presence of human lymphocyte and myeloid cell subsets within the tumors, lymph nodes, blood, and spleens in these models. Notably, these tumors exhibited a high prevalence of tumor-infiltrating macrophages. Furthermore, we identified HDAC class I target genes, and genes associated with epithelial-mesenchymal transition (EMT) and fibroblasts in the tumors of Hu-mice treated with pembrolizumab. Our xenograft Hu-mouse model of OC provides a valuable tool for investigating the efficacy of IO drugs. The insights gained from this model offer useful information to explore potential mechanisms associated with unresponsive anti-PD-1 treatment in OC.

Evaluation of the anti-cancer efficacy of lipid nanoparticles containing siRNA against HPV16 E6/E7 combined with cisplatin in a xenograft model of cervical cancer.

OBJECTIVE: To investigate the anti-cancer efficacy of ENB101-LNP, an ionizable lipid nanoparticles (LNPs) encapsulating siRNA against E6/E7 of HPV 16, in combination therapy with cisplatin in cervical cancer in vitro and in vivo. METHODS: CaSki cells were treated with ENB101-LNP, cisplatin, or combination. Cell viability assessed the cytotoxicity of the treatment. HPV16 E6/E7 gene knockdown was verified with RT-PCR both in vitro and in vivo. HLA class I and PD-L1 were checked by flow cytometry. A xenograft model was made using CaSki cells in BALB/c nude mice. To evaluate anticancer efficacy, mice were grouped. ENB101-LNP was given three times weekly for 3 weeks intravenously, and cisplatin was given once weekly intraperitoneally. Tumor growth was monitored. On day 25, mice were euthanized; tumors were collected, weighed, and imaged. Tumor samples were analyzed through histopathology, immunostaining, and western blot. RESULTS: ENB101-LNP and cisplatin synergistically inhibit CaSki cell growth. The combination reduces HPV 16 E6/E7 mRNA and boosts p21 mRNA, p53, p21, and HLA class I proteins. In mice, the treatment significantly blocked tumor growth and promoted apoptosis. Tumor inhibition rates were 29.7% (1 mpk ENB101-LNP), 29.6% (3 mpk), 34.0% (cisplatin), 47.0% (1 mpk ENB101-LNP-cisplatin), and 68.8% (3 mpk ENB101-LNP-cisplatin). RT-PCR confirmed up to 80% knockdown of HPV16 E6/E7 in the ENB101-LNP groups. Immunohistochemistry revealed increased p53, p21, and HLA-A expression with ENB101-LNP treatments, alone or combined. CONCLUSION: The combination of ENB101-LNP, which inhibits E6/E7 of HPV 16, with cisplatin, demonstrated significant anticancer activity in the xenograft mouse model of cervical cancer.

Pathological findings and long-term prognosis in Korean BRCA1/2 mutation carriers undergoing risk-reducing salpingo-oophorectomy.

OBJECTIVE: Our study aimed to evaluate the incidence of pathological findings in asymptomatic Korean patients with BRCA1/2 pathogenic variants who underwent risk-reducing salpingo-oophorectomy and to assess their long-term prognosis. METHODS: We retrospectively analyzed the medical records of patients with a germinal BRCA1/2 pathologic variant who had undergone risk-reducing salpingo-oophorectomy at Asan Medical Center (Seoul, Korea) between January 2013 and December 2020. All pathologic reports were made based on the sectioning and extensively examining the fimbriated end of the fallopian tube (SEE/FIM) protocol. RESULTS: Out of 243 patients who underwent risk-reducing salpingo-oophorectomy, 121 (49.8%) had a BRCA1 mutation, 119 (48.9%) had a BRCA2 mutation, and three (1.2%) had both mutations. During the procedure, four (3.3%) patients with a BRCA1 mutation were diagnosed with serous tubal intraepithelial carcinoma (STIC) or serous tubal intraepithelial lesion (STIL), and another four patients (3.3%) were diagnosed with occult cancer despite no evidence of malignancy on preoperative ultrasound. In the BRCA2 mutation group, we found one (0.8%) case of STIC, but no cases of STIL or occult cancer. During the median follow-up period of 98 months (range, 44-104) for STIC and 54 months (range, 52-56) for STIL, none of the patients diagnosed with these precursor lesions developed primary peritoneal carcinomatosis. CONCLUSIONS: Risk-reducing salpingo-oophorectomy, in asymptomatic Korean patients with BRCA1/2 pathogenic variants, detected ovarian cancer and precursor lesions, including STIC or STIL. Furthermore, our follow-up period did not reveal any instances of primary peritoneal carcinomatosis, suggesting a limited body of evidence supporting the imperative need for adjuvant treatment in patients diagnosed with these precursor lesions during risk-reducing salpingo-oophorectomy.

Chimeric Singleton Placenta Comprising Placental Mesenchymal Dysplasia and Complete Hydatidiform Mole with Live Birth and Postpartum Diagnosis of Gestational Trophoblastic Neoplasia.

INTRODUCTION: Placental mesenchymal dysplasia (PMD) is a benign lesion that is often misdiagnosed as complete (CHM) or partial hydatidiform mole. PMD usually results in live birth but can be associated with several fetal defects. Herein, we report PMD with CHM in a singleton placenta with live birth. CASE PRESENTATION: A 34-year-old gravida 2, para 1, living 1 (G2P1L1) woman was referred on suspicion of a molar pregnancy in the first trimester. Maternal serum human chorionic gonadotrophin levels were increased during early pregnancy, with multicystic lesions and placentomegaly observed on ultrasonography. Levels decreased to normal with no fetal structural abnormalities observed. A healthy male infant was delivered at 34 gestational weeks. Placental p57KIP2 immunostaining and short tandem repeat analysis revealed three distinct histologies and genetic features: normal infant and placenta, PMD, and CHM. Gestational trophoblastic neoplasia was diagnosed and up to fourth-line chemotherapy administered. CONCLUSION: Distinguishing PMD from hydatidiform moles is critical for avoiding unnecessary termination of pregnancy. CHM coexisting with a live fetus rarely occurs. This case is unique in that a healthy male infant was born from a singleton placenta with PMD and CHM.

A prospective randomized controlled trial evaluating the safety and efficacy of patient blood management program in patients with gynecologic cancer (KGOG 4011/PBM).

BACKGROUND: Gynecologic cancer has a high frequency of anemia, which is associated with increased morbidity and mortality. Blood transfusion is used to correct anemia, but carries its own side effects and problems in the blood supply have been emerging. As such, methods other than transfusion are needed to correct anemia in patients with cancer. PRIMARY OBJECTIVE: To determine whether intravenous administration of high-dose iron supplements before and after surgery as a patient blood management program is helpful in correcting anemia and reducing the frequency of transfusion in patients with gynecologic cancer. STUDY HYPOTHESIS: Patient blood management will reduce the transfusion rate by up to 25%. TRIAL DESIGN: This prospective, multicenter, interventional, randomized controlled study will consist of three steps. In step 1, the safety and effectiveness of patient blood management for surgical patients before, during, and after surgery will be evaluated. In steps 2 and 3, the safety and effectiveness of patient blood management in patients before, during, and after adjuvant radiation therapy and chemotherapy will be evaluated. MAJOR INCLUSION/EXCLUSION CRITERIA: Patients who are diagnosed with gynecologic cancer (ie, endometrial cancer, cervical cancer, ovarian cancer) and scheduled for surgery will be included and their iron deficiency status will be assessed. Only those with a pre-operative hemoglobin level of 7 g/dL or higher will be included. Patients who underwent neoadjuvant chemotherapy or pre-operative radiation therapy will be excluded. Also, patients with serum ferritin >800 ng/mL or transferrin saturation >50% on serum iron panel tests will be excluded. PRIMARY ENDPOINT: Rate of transfusion within 3 weeks after surgery. SAMPLE SIZE: Eligible participants will be randomly assigned in a 1:1 ratio (167 patients each) into the patient blood management group and the conventional management group. ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: Patient recruitment will be completed by mid-2025, and management and follow-up will be completed by the end of 2025. TRIAL REGISTRATION NUMBER: NCT05669872.

Laparo-endoscopic single-site versus conventional laparoscopic surgery for early-stage endometrial cancer: A randomized controlled non-inferiority trial.

OBJECTIVE: To evaluate the feasibility and safety of laparo-endoscopic single-site surgery (LESS) compared with conventional laparoscopic surgery (CLS) for early-stage endometrial cancer. METHODS: Patients with clinical stage IA, IB, grade 1-3 endometrial cancer were randomly assigned to undergo LESS or CLS. The primary endpoint was the non-inferiority of LESS to CLS in terms of operation time and the number of resected pelvic lymph nodes. We set the non-inferior margin of the operation time as within 15% (24 min) and the number of resected pelvic lymph nodes as within 20% (5.2 lymph nodes). RESULTS: There was no significant difference between the LESS group (n = 53) and the CLS group (n = 54) in terms of age, weight, body mass index, parity, menopausal status, history of abdominal surgery, and preoperative CA-125 levels. The total operation time was comparable between the two groups. On average, 4.6 fewer pelvic lymph nodes were retrieved in the LESS group, which was within the non-inferiority margin. There were no significant differences in the incidence of intra- and postoperative complications, estimated blood loss, and postoperative hospital stay between the two groups. After a median follow-up time of 34 months (range, 2-242), the progression-free survival rates were 96.2% and 98.1% (P = 0.55) in the LESS group and the CLS group, and the overall survival rates were 98.1% and 100.0% (P = 0.31), respectively. CONCLUSION: LESS surgical staging was non-inferior to CLS and had acceptable feasibility, safety, and efficacy for the surgical management of early-stage endometrial cancer. TRIAL REGISTRATION: Clinicaltrial.gov identifier number: NCT01679522.

Ruptured Hemorrhagic Ectopic Pregnancy Implanted in the Diaphragm: A Rare Case Report and Brief Literature Review.

The mortality and morbidity rates of non-tubal ectopic pregnancies with abdominal hemorrhaging are 7-8 times higher than those of tubal pregnancies. Diaphragmatic pregnancy is a rare non-tubal ectopic form, causing acute abdominal hemoperitoneum. Here, we present a case of a primary diaphragmatic ectopic pregnancy with hemorrhage that was immediately diagnosed and successfully managed with laparoscopic surgery. Rapid and accurate diagnosis using appropriate imaging modalities is critical for improving the prognosis of a child-bearing woman with an abdominal pregnancy.

Novel Technique for the Measurement of Fetal Right Modified Myocardial Performance Index Using Synchronized Images of Right Ventricular Inflow and Outflow and Clinical Application to Twin-to-Twin Transfusion Syndrome.

OBJECTIVE: To evaluate the reproducibility of the fetal right modified myocardial performance index (Mod-MPI) obtained by synchronizing the inflow and outflow images of the right ventricle (RV) and to evaluate its feasibility through clinical application to twin-to-twin transfusion syndrome (TTTS). METHODS: We prospectively evaluated 77 normal fetuses. Two experienced operators individually measured the right Mod-MPI using two different methods: (1) separate recording of the RV inflow and outflow using pulsed-wave Doppler (conventional method) and (2) synchronization of RV inflow and outflow images using the MPI + ™ function based on the closure click of the pulmonary valve (new method). To evaluate the clinical utility of the new method, we measured the right Mod-MPI in 33 TTTS fetuses using the new method before and after the fetoscopic laser coagulation (FLC). RESULTS: There was no statistical difference in Mod-MPI values between the two methods (p = .242). For both operators, the intra- and interoperator reproducibility of Mod-MPI was high with both methods (ICCs >0.950). Among the components of Mod-MPI measured using the new method, ejection time showed the highest reproducibility, whereas isovolumetric relaxation time demonstrated the lowest reproducibility. In TTTS fetuses, the Mod-MPI significantly decreased after FLC in recipients, and there was no difference in MPI values before and after FLC in donors. CONCLUSION: Right Mod-MPI measurement after the synchronization of RV inflow and outflow images is a reliable technique for evaluating fetal right cardiac function. This novel method can also independently evaluate the systolic and diastolic functions of the right heart.

Perinatal outcome of fetuses with congenital high airway obstruction syndrome: a single-center experience.

OBJECTIVE: To report our experience with management of fetuses with congenital high airway obstruction syndrome (CHAOS). METHODS: We retrospectively reviewed the cases of fetuses who were prenatally diagnosed and postnatally confirmed with CHAOS between 2010 and 2019 at Asan Medical Center, Seoul, Korea. RESULTS: Of 13 fetuses prenatally diagnosed with CHAOS, 7 were lost to follow-up and 6 were postnatally confirmed as having CHAOS. All fetuses, except one were delivered via cesarean section with an ex utero intrapartum treatment (EXIT) procedure. Two patients had coexisting congenital heart diseases requiring several cardiac surgeries following birth. Both of these patients demonstrated developmental delay; however, the remaining 4 had a normal development except for expressive language. Two infants died of respiratory complications, and the remaining 4 were alive at the end of the follow-up period. All 4 live patients underwent tracheostomy with planned reconstruction surgery. Three children are now able to phonate, and 1 can maintain a conservation. CONCLUSION: The proper management of CHAOS using the EXIT procedure results in high survival and low hypoxemia-induced complication rates. Therefore, an accurate prenatal diagnosis is necessary for an appropriate perinatal management.

Distribution of free, esterified, and insoluble bound forms of phenolics in tea seeds and their antioxidant activity.

In this study, phenolic compounds in their phenolic extract (PE), free phenolic (FP), esterified phenolic (EFP), and insoluble bound phenolic (ISBP) forms were extracted from tea seeds and quantified using HPLC to obtain information on the phenolics that are present in tea seeds along with their antioxidant activities. The total phenolic content of the ISBP fraction was higher than that of the FP and EFP fractions. The phenolic acids in tea seeds exist either in esterified or glycosided forms. Moreover, hydroxycinnamic acid derivatives have been identified as important phenolic acid components in tea seeds. The ISBP fraction was an effective antioxidant based on the results obtained from the in vitro assays performed, which include the DPPH and 2,2-azinobis(3-ethylbenzothiazoline-6-sulfonic acid)-derived nitrogen-centered radical scavenging activities, Fe3+-2,4,6-tripyridyl-s-triazine reducing ability, as well as Cu2+ and Fe2+ ion chelating effects.

Physicochemical Characteristics of Black Garlic after Different Thermal Processing Steps.

This study investigated the physicochemical characteristics of black garlic (BG) after different thermal processing steps. Compared with fresh garlic (FG), the moisture content and pH in BG decreased significantly, while the ash content and browning intensity increased during thermal processing. The total mineral and the free sugar contents were significantly higher than that of the BG2 and BG4 samples, respectively. The free sugar content increased by 16-fold in the BG cloves compared with that of FG, while the amino acid content increased during the first stage of thermal processing, and subsequently decreased. The thiosulfinate content in all samples decreased to during thermal processing. The pyruvic acid content initially increased and then decreased during thermal processing. These results contribute to our understanding of the role of thermal processing in the quality formation of BG.

Comparison of Ginsenoside Contents in Different Parts of Korean Ginseng (Panax ginseng C.A. Meyer).

The present study was conducted to investigate the ginsenoside profiles of the main root, root hair, and leaf of ginseng in order to demonstrate their possible application in medicine. The total ginsenoside content of the leaf was up to 12 times than that in the main root, and the content of protopanaxadiol groups was higher than that of protopanaxatriol groups in all the samples. The leaf was shown to contain high amounts of ginsenosides Rb3 and Rh1, whereas the main root contained large amounts of ginsenosides Rb1 and Rc. Moreover, Rb2, Rb3, and Rg1 were only detected in the root hair, leaf, and main root, respectively. The ginsenoside Re content of Panax ginseng leaf and root hair was 2.6~4 times higher than that of the main root. Therefore, the results indicate that the ginsenoside content of Panax ginseng is higher in the leaf and root hair, and lower in the main root.

Evaluation of Melanoidins Formed from Black Garlic after Different Thermal Processing Steps.

The objective of this study was to evaluate the characteristics of melanoidins formed from black garlic (BG) after different thermal processing steps. The melanoidins formed from BG during thermal processing were produced in large amounts, and the initial (280 nm), intermediate (360 nm), and final stage product (420 nm) had similar tendencies. Compounds like degraded proteins, peptides, and phenolic acids were present in the melanoidins during thermal processing. All the melanoidin samples showed different absorptions in the UV-visible spectra, although these had similar shapes. Moreover, the carbon, hydrogen, and oxygen content of melanoidins formed from BG during thermal processing decreased initially, and then increased. However, the nitrogen content increased during thermal processing. As thermal processing progressed, the molecular weight of all the melanoidin samples showed increasing intensities, whereas the major peaks of each melanoidin sample had different retention times. Furthermore, the melanoidins formed from BG after different thermal processing steps contained -OH, -CH, amide I, and III groups. The crystallinity of the melanoidins was majorly formed at 31.58° and 43.62° (2θ).