Practice guidelines for management of uterine corpus cancer in Korea: a Korean Society of Gynecologic Oncology consensus statement.

The Korean Society of Gynecologic Oncology (KSGO) had been making an effort to standardize and enhance the quality of domestic uterine corpus cancer treatment by developing updated clinical practice guidelines in 2021. The KSGO revised the guidelines based on a literature search using 4 key elements: Population, Intervention, Comparison, and Outcome framework. These elements include the evaluation of the efficacy and safety of immune checkpoint inhibitor treatment in recurrent/advanced endometrial cancer patients who have failed platinum-based chemotherapy, as well as the effect of combined treatment with trastuzumab in patients with HER2/neu-positive endometrial cancer. Additionally, the guideline assessed the efficacy and safety of omitting lymph node dissection in low-risk endometrial cancer patients, investigated the effect of sentinel lymph node mapping in early-stage endometrial cancer surgery, addressed the outcome of chemoradiation therapy as a postoperative treatment in patients with advanced (stage III-IVA) endometrial cancer, and explored the impact of initial treatment with immune checkpoint inhibitors on survival in patients with advanced or recurrent endometrial cancer patients.

Immune checkpoint inhibitors with chemotherapy for primary advanced mismatch repair-deficient endometrial cancer: A cost-effectiveness analysis.

OBJECTIVE: The addition of immune checkpoint inhibitors (ICIs), pembrolizumab or dostarlimab, to paclitaxel and carboplatin (TC) has shown better response rates and survival outcomes for patients with primary advanced mismatch repair-deficient (MMRd) endometrial cancer (EC) in NRG-GY018 and RUBY, respectively. Nonetheless, the high cost of ICIs remains a major concern when implementing this strategy in the real world. This study aimed to determine the cost-effectiveness of pembrolizumab and dostarlimab with chemotherapy compared to TC for primary advanced MMRd EC. METHODS: We developed a Markov model including 6600 patients with primary advanced MMRd EC to simulate treatment outcomes. The initial decision points in the model were treatment with pembrolizumab with TC (PEM-TC), dostarlimab with TC (DOS-TC), and TC. Model probabilities, costs, and health utility values were derived with assumptions from published literature. Effectiveness was determined as average quality-adjusted life years (QALYs) gained. The primary outcome was the incremental cost-effectiveness ratio (ICER). RESULTS: TC was the least costly strategy, whereas PEM-TC was the most effective strategy for primary advanced MMRd EC. TC was cost-effective based on a willingness-to-pay (WTP) threshold of $100,000/QALY compared with PEM-TC (ICER, $377,718/QALY), and DOS-TC exhibited absolute dominance (ICER, $401,859/QALY). PEM-TC was cost-effective when the cost of pembrolizumab 200 mg was reduced to $4361 (61% reduction). PEM-TC was selected in 16.5% with a WTP threshold of $300,000/QALY, but in <1% with a WTP threshold range of $100,000-200,000/QALY. CONCLUSION: PEM-TC can become cost-effective for primary advanced MMRd EC when the cost of pembrolizumab substantially decreases.

Degradation of phenol by perborate in the presence of iron-bearing and carbonaceous materials.

We investigated the oxidation of phenol by perborate-a newly proposed oxidant-in the presence of iron-bearing and carbonaceous materials through batch experiments. We hypothesized that the oxidation of phenol by perborate was enhanced due to the formation of reactive oxygen species (ROS) in the presence of iron-bearing or carbonaceous materials. Zero-valent iron and ferrous iron (Fe2+) promoted the oxidation of phenol by perborate. Biochar, granular activated carbon, an anode carbonaceous material recovered from a spent Li-ion battery, and graphite also accelerated the oxidation of phenol by perborate. Quenching experiments with radical scavengers and electron paramagnetic resonance (EPR) analysis revealed that hydroxyl (˙OH) and superoxide (O2˙-) radicals were generated and enhanced the degradation of phenol in the perborate systems. Singlet oxygen (1O2) was involved in the iron-bearing material-perborate systems. Moreover, we found that Persil®, a commercial perborate detergent, enhances the oxidation of phenol in the presence of iron-bearing and carbonaceous materials. Our results suggest that perborate can be used for advanced oxidation processes to remediate recalcitrant organic contaminants in natural environments and engineered systems.

Review of cadmium toxicity effects on fish: Oxidative stress and immune responses.

Cadmium (Cd) in aquatic environments can cause environmental toxicity to fish and induce oxidative stress owing to an excessive production of reactive oxygen species in fish bodies. Fish have developed various antioxidant systems to protect themselves from reactive oxygen species; thus, a change in antioxidant responses in fish can be a criterion for evaluating oxidative stress resulting from Cd exposure. Because Cd exposure may be recognized as an exogenous substance by a fish body, it may lead to the stimulation or suppression of its immune system. Various immune responses can be assessed to evaluate Cd toxicity in fish. This review aimed to identify the impacts of Cd exposure on oxidative stress and immunotoxicity in fish as well as identify accurate indicators of Cd toxicity in aquatic ecosystems.

Toxic effects of sub-acute microplastic (polyamide) exposure on the accumulation, hematological, and antioxidant responses in crucian carp, Carassius carassius.

The purpose of this study is to investigate the impact of microplastics (MPs) on fish and to confirm the toxic effects of MPs on fish, as well as to clarify the standard indicators. MPs are present in a large amount in the aquatic environment and can have various adverse effects on aquatic animals. Crucian carp, Carassius carassius (mean weight, 23.7 ± 1.6 g; mean length, 13.9 ± 1.4 cm), were exposed to PA (Polyamide) concentrations of 0, 4, 8, 16, 32 and 64 mg/L for 2 weeks. The PA accumulation profile in C. carassius decreased from the intestine to the gill to the liver. Hematological parameters such as red blood cell (RBC) counts, hemoglobin (Hb), and hematocrit (Ht) notably decreased at high levels of PA exposure. Plasma components such as calcium, magnesium, glucose, cholesterol, total protein, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) were significantly altered by PA exposure. The activities of superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST) and glutathione (GSH) of liver, gill and intestine significantly increased following PA exposure. The results of this study suggest that MP exposure affects the hematological physiology and antioxidant responses in C. carassius as well as accumulation in specific tissues.

Prognostic significance of L1CAM expression in addition to ProMisE in endometrial cancer.

OBJECTIVE: To investigate the prognostic significance of L1 cell-adhesion molecule (L1CAM), ß-catenin, and programmed death-ligand 1 (PD-L1) in endometrial cancer (EC) patients, with a focus on p53 wild-type subgroup, for additional risk stratification. METHODS: This retrospective cohort study included EC patients classified according to Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE) who underwent primary surgical treatment at the single center between January 2014 and December 2018. Immunohistochemical staining was performed for four mismatch repair (MMR) proteins, p53, L1CAM, ß-catenin, and PD-L1. DNA polymerase epsilon (POLE) mutation was detected by hot spot sequencing via droplet digital polymerase chain reaction. Survival outcome of each subgroup of L1CAM, ß-catenin, and PD-L1 was measured according to their expression. RESULTS: A total of 162 EC patients were included. Endometrioid histologic type and early-stage disease were 140 (86.4%) and 109 (67.3%), respectively. ProMisE classification assigned 48 (29.6%), 16 (9.9%), 72 (44.4%), and 26 (16.0%) patients to MMR-deficient, POLE-mutated, p53 wild-type, and p53 abnormal subgroups, respectively. L1CAM was identified as an independent poor prognostic factor for progression-free survival (PFS; adjusted hazard ratio [aHR], 3.207; 95% confidence interval (CI), 1.432-7.187; P = 0.005), whereas ß-catenin and PD-L1 positivity were not associated with recurrence (P = 0.462 and P = 0.152, respectively). In p53 wild-type subgroup, L1CAM positivity was associated with worse PFS (aHR, 4.906; 95% CI, 1.685-14.287; P = 0.004). CONCLUSION: L1CAM positivity was associated with poor prognosis in EC and further stratified the risk of recurrence in p53 wild-type subgroup, whereas ß-catenin and PD-L1 were not informative for risk stratification.

Toxic effects of microplastic (polyethylene) exposure: Bioaccumulation, hematological parameters and antioxidant responses in crucian carp, Carassius carassius.

The purpose of this study was to evaluate the toxic effects of polyethylene microplastics (PE-MPs) by measuring the bioaccumulation, hematological parameters, and antioxidant responses in crucian carp (Carassius Carassius) exposed to waterborne 22-71 µm PE-MPs. C. carassius (mean weight, 24.0 ± 2.1 g; mean length, 13.1 ± 1.2 cm) were exposed to PE-MPs at concentration of 0, 4, 8, 16, 32, and 64 mg/L for 2 weeks. The accumulation of PE-MPs in each tissue of C. carassius was significantly increased in proportion to the PE-MPs concentration; the highest accumulation was observed in the intestine, followed by the gills and liver. Hematological parameters, plasma components and antioxidants responses were significantly affected by PE-MPs in a concentration-dependent manner. Exposure to ≥32 mg/L PE-MPs induced a significant decrease in red blood cells (RBCs), hemoglobin (Hb) content, and hematocrit values. However, exposure to ≥32 mg/L PE-MPs induced oxidative stress in the liver, gill, and intestine of C. carassius, thereby resulting in a significant increase in the levels of superoxide dismutase (SOD), catalase (CAT), and glutathione S-transferase (GST) and a decrease in glutathione (GSH) levels. The effects of interaction between the PE-MPs and exposure periods showed no significant changes in bioaccumulation, hematological parameters, plasma components and antioxidant responses. These finding indicate that the exposure to ≥32 mg/L PE-MPs could cause a significant accumulation in specific tissues of C. carassius, resulting in changes in hematological parameters, plasma components, and antioxidant responses. However, the interaction between PE-MPs and exposure periods had no significant effects, thereby suggesting the lack of toxicological interactions between PE-MPs and exposure periods in C. carassius.

The mercury accumulation and its effects on antioxidant and immune responses in starry flounder, Platichthys stellatus exposed to dietary mercury.

The purpose of this study is to investigate the effect of inorganic mercury (Hg) on fish. Inorganic Hg is less toxic than organic Hg, but it is used more in human daily life, such as manufacturing Hg batteries and fluorescent lamps. For this reason, inorganic Hg was used in this study. Starry flounder, Platichthys stellatus (mean weight 43.9 ± 4.4 g; mean length 14.2 ± 0.4 cm) were exposed for 4 weeks to the different levels of dietary inorganic Hg at concentrations of 0, 4, 8, 12 and 16 mg Hg/kg, and depuration was performed for 2 weeks after exposure. Bioaccumulation of Hg in the tissues was observed to increase significantly, in following order: intestine > head kidney > liver > gills > muscle. Antioxidant responses (superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST) and glutathione (GSH)) were significantly increased. Immune responses (lysozyme and phagocytosis activity) were substantially decreased. The results of this study suggest that dietary inorganic Hg induces bioaccumulation in specific tissues, increases antioxidant responses and decreases immune responses. After the depuration period for 2 weeks, it was effective to alleviate bioaccumulation in tissues. However, antioxidant and immune responses were limited to be attenuated for recovery.

Diagnostic imaging of adnexal masses in pregnancy.

Adnexal masses detected during pregnancy require a prompt and accurate diagnosis to ensure fetal safety and good oncological outcomes. Computed tomography is the most common and useful diagnostic imaging modality for diagnosing adnexal masses; however, it is contraindicated in pregnant women because of the teratogenic effect of radiation on the fetus. Therefore, ultrasonography (US) is commonly used as the main alternative for the differential diagnosis of adnexal masses during pregnancy. Additionally, magnetic resonance imaging (MRI) can assist in the diagnosis when US findings are inconclusive. As each disease has characteristic US and MRI findings, understanding these features is important for the initial diagnosis and subsequent treatment. Thus, we thoroughly reviewed the literature and summarized the key findings of US and MRI to apply these in real-world clinical practice for various adnexal masses detected during pregnancy.

Exogenous mitochondrial transplantation improves survival and neurological outcomes after resuscitation from cardiac arrest.

BACKGROUND: Mitochondrial transplantation (MTx) is an emerging but poorly understood technology with the potential to mitigate severe ischemia-reperfusion injuries after cardiac arrest (CA). To address critical gaps in the current knowledge, we test the hypothesis that MTx can improve outcomes after CA resuscitation. METHODS: This study consists of both in vitro and in vivo studies. We initially examined the migration of exogenous mitochondria into primary neural cell culture in vitro. Exogenous mitochondria extracted from the brain and muscle tissues of donor rats and endogenous mitochondria in the neural cells were separately labeled before co-culture. After a period of 24 h following co-culture, mitochondrial transfer was observed using microscopy. In vitro adenosine triphosphate (ATP) contents were assessed between freshly isolated and frozen-thawed mitochondria to compare their effects on survival. Our main study was an in vivo rat model of CA in which rats were subjected to 10 min of asphyxial CA followed by resuscitation. At the time of achieving successful resuscitation, rats were randomly assigned into one of three groups of intravenous injections: vehicle, frozen-thawed, or fresh viable mitochondria. During 72 h post-CA, the therapeutic efficacy of MTx was assessed by comparison of survival rates. The persistence of labeled donor mitochondria within critical organs of recipient animals 24 h post-CA was visualized via microscopy. RESULTS: The donated mitochondria were successfully taken up into cultured neural cells. Transferred exogenous mitochondria co-localized with endogenous mitochondria inside neural cells. ATP content in fresh mitochondria was approximately four times higher than in frozen-thawed mitochondria. In the in vivo survival study, freshly isolated functional mitochondria, but not frozen-thawed mitochondria, significantly increased 72-h survival from 55 to 91% (P = 0.048 vs. vehicle). The beneficial effects on survival were associated with improvements in rapid recovery of arterial lactate and glucose levels, cerebral microcirculation, lung edema, and neurological function. Labeled mitochondria were observed inside the vital organs of the surviving rats 24 h post-CA. CONCLUSIONS: MTx performed immediately after resuscitation improved survival and neurological recovery in post-CA rats. These results provide a foundation for future studies to promote the development of MTx as a novel therapeutic strategy to save lives currently lost after CA.

Toxic effects of microplastic (Polyethylene) on fish: Accumulation, hematological parameters and antioxidant responses in Korean Bullhead, Pseudobagrus fulvidraco.

Plastic waste discharged into the aquatic environment decomposes into microplastics (MP), which have toxic effects on fish species. Korean bullhead, Pseudobagrus fulvidraco is widely distributed in freshwater ecosystems in Korea, and it is important as an ecological indicator species to evaluate MP toxicity in Korea. In this study, the accumulation and physiological effects of juvenile P. fulvidraco exposed to microplastics (Polyethylene: PE-MPs with white surface and spherical shape) at control (0 mg/L), 100, 200, 5000 and 10,000 mg/L for 96 h were confirmed. Exposure to PE-MPs showed significant bioaccumulation of P. fulvidraco, and the accumulation profile was in the order of gut > gills > liver. Hematological parameters such as the red blood cell (RBC), hemoglobin (Hb) and hematocrit (Ht) were significantly decreased over 5000 mg/L In plasma components, calcium, magnesium and total protein were significantly decreased over 5000 mg/L, whereas glucose, cholesterol, aspartate aminotransferase (AST), alanine transaminase (ALT) and alkaline phosphatase (ALP) were significantly increased over 5000 mg/L or at 10,000 mg/L In antioxidant responses, superoxide dismutase (SOD), catalase (CAT) and glutathione S-transferase (GST) were significantly increased over 5000 mg/L, whereas glutathione (GSH) was significantly decreased over 5000 mg/L. The results of this study suggest that acute exposure to PE-MPs induced all physiological changes in a concentration-dependent manner, and it affects the hematological parameters, plasma components and antioxidant response of juvenile P. fulvidraco after accumulation in specific tissues.

Development and Validation of 18F-FDG PET/CT-Based Models for Predicting Successful Complete Cytoreduction During Primary Cytoreductive Surgery for Advanced Ovarian cancer.

PURPOSE: The aim of this study was to develop an 18F-FDG PET/CT-based model to predict complete cytoreduction during primary cytoreductive surgery (CRS) for ovarian cancer (OC). PATIENTS AND METHODS: We retrospectively identified patients with stage III-IV OC who underwent primary CRS between June 2013 and February 2020 at 2 tertiary centers. Patients from each hospital were assigned to training and test sets. The abdominal cavity was divided into 3 sections, and data for the PET/CT-derived parameters were collected through image analysis. Various prediction models were constructed by combining clinicopathologic characteristics and PET/CT-derived parameters. The performance of the model with the highest area under the receiver operating characteristic curve (AUC) was externally validated. RESULTS: The training and test sets included 159 and 166 patients, respectively. The median age of patients in the test set was 55 years; 72.3% of them had stage III tumors, and 65.4% underwent complete cytoreduction. Metabolic tumor volume, total lesion glycolysis, and the number of metastatic lesions above the upper margin of the renal vein (area A) were selected among the PET/CT parameters. The best predictive multivariable model consisted of CA-125 (<750 or ≥750 IU/mL), number of metastatic lesions (<2 or ≥2), and metabolic tumor volume of area A, predicting complete cytoreduction with an AUC of 0.768. The model was validated using a test set. Its predictive performance yielded an AUC of 0.771. CONCLUSIONS: We successfully developed and validated a preoperative model to predict complete cytoreduction in advanced OC. This model can facilitate patient selection for primary CRS in clinical practice.

Effects on Bioaccumulation, Growth Performance, Hematological Parameters, Plasma Components, and Antioxidant Responses in Starry Flounder (Platichthys stellatus) Exposed to Dietary Cadmium and Ascorbic Acid.

This study evaluates the toxic effects of dietary Cd and mitigative effects of AsA supplementation by measuring the growth performance, bioaccumulation, hematological parameters, plasma components, and antioxidant responses of Starry flounder (Platichthys stellatus). Platichthys stellatus (mean weight, 69.5 ± 1.4 g; mean length, 18.2 ± 0.21 cm) was fed with dietary cadmium-ascorbic acid (Cd-AsA) composed of C0A0, C0A500, C0A1000, C40A0, C40A500, C40A1000, C80A0, C80A500, and C80A1000 mg of Cd-AsA per kg diet for four weeks. Our results showed that Cd accumulation significantly increased in proportion to the Cd concentration, where the highest levels were observed in the intestine, followed by the kidney, liver, and gills. Dietary AsA significantly mitigated the Cd accumulation in all tissues, and the reduction in Cd accumulation was proportional to the increase in AsA concentration. Dietary Cd has adverse effects on growth performance (body weight gain, specific growth rate, feed conversion ratio, and hepatosomatic index) and can alter the hematological parameters (red blood cell count, hematocrit, and hemoglobin), plasma components (glucose, total protein, glutamic oxaloacetic transaminase, and glutamic pyruvic transaminase), and antioxidant responses (superoxide dismutase, catalase, glutathione S-transferase, and glutathione). Dietary AsA restored the decreased growth performance parameters and the altered hematological parameters, plasma components, and antioxidant responses caused by the dietary Cd exposure. The results of this study showed that dietary Cd is toxic to P. stellatus, while dietary AsA is effective in mitigating the toxic effects of Cd.

Detoxification effects of ascorbic acid on the oxidative stress, neurotoxicity, and metallothionein (MT) gene expression in juvenile rockfish, Sebastes schlegelii by the dietary chromium exposure.

Juvenile rockfish Sebastes schlegelii (mean length 10.8 ± 1.4 cm, and mean weight 31.7 ± 3.6 g) were exposed for 4 weeks with the different levels of dietary chromium (Cr6+) at 0, 120 and 240 mg/L and ascorbic acids (AsA) at 100, 200 and 400 mg/L. Superoxide dismutase (SOD) activity, glutathione S-transferase (GST) activity, and glutathione (GSH) level of liver and gill were evaluated as antioxidant response indicators for the 4 weeks exposure. The SOD and GST activity of liver and gill were substantially increased by the high concentrations of dietary Cr exposure, whereas a significant decrease was observed in the GSH levels of liver and gill. Metallothionein (MT) gene in liver was significant stimulated in the response to the dietary Cr exposure. In neurotoxicity, AChE activity was considerably inhibited in brain and muscle tissues by dietary Cr exposure. The high levels of AsA supplementation were highly effective to attenuate the alterations in the antioxidant responses, MT gene expression, and AChE activity by the dietary Cr exposure.

Metabolic Syndrome as a Risk Factor of Endometrial Cancer: A Nationwide Population-Based Cohort Study of 2.8 Million Women in South Korea.

Background: A positive relationship was reported between metabolic syndrome and the risk of endometrial cancer. Studies on the relationship between metabolic syndrome and endometrial cancer have been mainly conducted in post-menopausal women. We aimed to investigate the risk of endometrial cancer according to metabolic syndrome and menopausal status using the Korean nationwide population-based cohort. Methods: We enrolled 2,824,107 adults (endometrial cancer group; N = 5,604 and control group; N= 2,818,503) from the Korean National Health Insurance Service checkup database from January 1 to December 31, 2009. The median follow-up duration was 8.37 years. Metabolic syndrome was diagnosed as having at least three of the following five components: abdominal obesity, hypertriglyceridemia, low levels of high-density lipoprotein cholesterol, raised blood pressure, and hyperglycemia. Multivariate Cox proportional hazard models were used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) to estimate endometrial cancer risk. Results: The endometrial cancer risk was higher in the metabolic syndrome group than that in the non-metabolic syndrome group (HR, 1.362; 95% CI, 1.281-1.449). The association between metabolic syndrome and endometrial cancer risk was significant in the premenopausal subgroup (HR, 1.543; 95% CI, 1.39-1.713) and postmenopausal subgroup (HR, 1.306; 95% CI, 1.213-1.407). The incidence of endometrial cancer was more closely related to metabolic syndrome components in the pre-menopausal subgroup than those in the post-menopausal subgroup (for waist circumference, blood pressure, triglycerides and high-density lipoprotein cholesterol, all p for interaction <0.0001 respectively, and for fasting blood glucose, p for interaction 0.0188). The incidence of endometrial cancer positively correlated with the number of metabolic syndrome components (log-rank p <0.0001). Conclusion: Our large population-based cohort study in Korean women suggests that metabolic syndrome and its accumulated components may be risk factors for endometrial cancer, particularly in the pre-menopausal women.

Clinical Features and Risk Factors of Adrenal Insufficiency in Patients With Cancer Admitted to the Hospitalist-Managed Medical Unit.

BACKGROUND: The symptoms of adrenal insufficiency (AI) overlap with the common effects of advanced cancer and chemotherapy. Considering that AI may negatively affect the overall prognosis of cancer patients if not diagnosed in a timely manner, we analyzed the incidence, risk factors, and predictive methods of AI in cancer patients. METHODS: We retrospectively analyzed the medical records of 184 adult patients with malignancy who underwent a rapid adrenocorticotrophic hormone stimulation test in the medical hospitalist units of a tertiary hospital. Their baseline characteristics and clinical features were evaluated, and the risk factors for AI were identified using logistic regression analysis. RESULTS: Of the study patients, 65 (35%) were diagnosed with AI, in whom general weakness (63%) was the most common symptom. Multivariate logistic regression showed that eosinophilia (adjusted odds ratio [aOR], 4.28; 95% confidence interval [CI], 1.10-16.63; P = 0.036), history of steroid use (aOR, 2.37; 95% CI, 1.10-5.15; P = 0.028), and history of megestrol acetate use (aOR, 2.71; 95% CI, 1.38-5.33; P = 0.004) were associated with AI. Baseline cortisol levels of 6.2 µg/dL and 12.85 µg/dL showed a specificity of 95.0% and 95.4% for AI diagnosis, respectively. CONCLUSION: AI was found in about one-third of patients with cancer who showed general symptoms that may be easily masked by cancer or chemotherapy, suggesting that clinical suspicion of AI is important while treating cancer patients. History of corticosteroids or megestrol acetate were risk factors for AI and eosinophilia was a pre-test predictor of AI. Baseline cortisol level appears to be a useful adjunct marker for AI.

Safety and feasibility of laterally extended endopelvic resection for sarcoma in the female genital tract: a prospective cohort study.

OBJECTIVE: This study aims to evaluate the safety and feasibility of laterally extended endopelvic resection (LEER) for sarcoma in the female genital tract. METHODS: We prospectively recruited gynecologic cancer patients with sarcoma arising from female genital tract who underwent LEER at Seoul National University Hospital from December 2016 to March 2021. Clinicopathologic characteristics, surgical outcomes including postoperative complications and pain control, and survival outcomes of the patients were investigated. RESULTS: A total of nine patients were registered for this study. The median age was 56 years. Carcinosarcoma (n=2, 22%), leiomyosarcoma (n=2, 22%), and undifferentiated uterine sarcoma (n=2, 22%) were common histology types. Complete resection was achieved in 88.9%. The most common location of pelvic sidewall tumors was infra-iliac acetabulum (66.7%). The pathologic outcome showed a median tumor size of 9.0 cm and internal iliac vessel resection with pelvic sidewall muscle was performed in all patients. The median estimated blood loss was 1,600 mL (range, 300-22,300), and the patients were postoperatively admitted to the intensive care unit for median 1 day (range, 0-8). Complete response was observed in 44.4% (4/9) in radiologic studies after LEER, and median progression-free survival, treatment-related survival, and overall survival were 3.3, 19.6, and 98.9 months, respectively. CONCLUSION: LEER was feasible and safe in treating recurrent sarcoma presenting pelvic sidewall invasion with acceptable survival outcomes and manageable postoperative complications.

Integrated analysis of ascites and plasma extracellular vesicles identifies a miRNA-based diagnostic signature in ovarian cancer.

Ovarian cancer is mostly diagnosed at advantaged stages due to the lack of early diagnostic biomarkers. The common metastasis pattern is characterized by peritoneal dissemination with a formation of malignant ascites. Extracellular vesicles (EVs) are emerging as promising clinical biomarkers in liquid biopsy. Here, we aimed to investigate robust liquid biopsy-based EV miRNA biomarkers for ovarian cancer diagnosis and metastasis regulation. EVs were isolated from malignant ascites and plasma of ovarian cancer patients as well as the benign control counterparts of patients with benign gynecologic diseases. EV small RNA sequencing identified a panel of eight miRNAs (miR-1246, miR-1290, miR-483, miR-429, miR-34b-3p, miR-34c-5p, miR-145-5p, miR-449a) based on dysregulated miRNAs overlapped in the ascites and plasma subset. The ovarian cancer EV miRNA (OCEM) signature developed based on these eight miRNAs demonstrated high diagnostic accuracy in our in-house dataset and multiple public datasets across diverse clinical samples (blood, tissue and urine). In addition, malignant ascites-derived EVs could significantly facilitate the aggressive property of ovarian cancer cells and boost the growth of ascites-derived organoids. Notably, miR-1246 and miR-1290 shuttled in malignant ascites-derived EVs were identified to promote the invasion and migration of ovarian cancer cells through regulating a common target RORα.

Real-world experience of pembrolizumab and lenvatinib in recurrent endometrial cancer: A multicenter study in Korea.

OBJECTIVE: To investigate the effectiveness and safety of pembrolizumab and lenvatinib (PEMBRO+LEN) for recurrent endometrial cancer (EC) in a real-world setting. METHODS: This multicenter retrospective cohort study included patients with recurrent EC who received PEMBRO+LEN between March 2020 and May 2021 at three tertiary hospitals in Korea. We summarized patient characteristics and evaluated the response rates, survival outcomes, and treatment-related adverse events (AEs). RESULTS: In total, 48 patients were included in the study. The median age of the patients was 62.5 (range, 42-78) years. The most common histologic subtype was endometrioid adenocarcinoma (43.8%), followed by serous adenocarcinoma (25.0%). Most patients (91.7%) had mismatch repair-proficient tumors. Patients received PEMBRO+LEN for a median of 4.5 cycles, during which the best objective response rate and disease control rate were 23.8% (95% CI, 11.9-38.1) and 76.2% (95% CI, 61.9-88.1), respectively. Overall, 56.2% of patients experienced LEN dose reduction once or more and 16.7% experienced LEN interruption. The most common treatment-related AEs were fatigue (18.8%), hypertension (16.7%), and hypothyroidism (14.6%). Total of 8 patients (16.7%) discontinued LEN during the treatment because of treatment-related AEs. Serum CA-125 level was the only prognostic factor for progression-free survival (adjusted hazard ratio, 4.41; 95% confidence interval, 1.19-16.36; p = 0.03). CONCLUSIONS: In our real-world study, Korean patients with recurrent EC who received PEMBRO+LEN showed lower treatment response rate and similar treatment discontinuation rate, compared to clinical trials.

Toxic effects of waterborne cadmium exposure on hematological parameters, oxidative stress, neurotoxicity, and heat shock protein 70 in juvenile olive flounder, Paralichthysolivaceus.

Cadmium-induced toxicity can affect fish embryo development, ion homeostasis regulation, energy metabolism, maturation and growth, stress response, and immunity. However, studies on the toxic effects of cadmium exposure to aquatic animals, particularly olive flounder (Paralichthys olivaceus), are limited. In this study, juvenile P. olivaceus (mean length, 12.9 ± 1.3 cm; mean weight, 23.1 ± 3.2 g) was exposed to waterborne cadmium (0, 50, 100, 200, and 400 µg/L) for 10 d. Hematological parameters, including hematocrit value and hemoglobin level, in P. olivaceus were significantly decreased after waterborne cadmium exposure. Plasma components such as calcium, glucose, cholesterol, glutamic-oxaloacetic transaminase, and glutamic-pyruvic transaminase were significantly altered via cadmium exposure. The activities of antioxidant enzymes, such as superoxide dismutase, catalase, and glutathione S-transferase, were significantly altered in P. olivaceus after cadmium exposure. Acetylcholinesterase activity was significantly inhibited upon waterborne cadmium exposure. Hepatic heat shock protein 70 was significantly upregulated in P. olivaceus after waterborne cadmium exposure. Therefore, waterborne cadmium at concentrations of >100 or 200 µg/L can induce physiological toxicity in P. olivaceus via changes in hematological parameters, antioxidant enzymes, neurotransmitters, and stress indicators.