G Protein-Coupled Estrogen Receptor-Mediated Anti-Inflammatory and Mucosal Healing Activity of a Trimethylpyridinol Analogue in Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is characterized by abnormal immune responses, including elevated proinflammatory cytokines, such as tumor necrosis factor-α (TNFα) and interleukin-6 (IL-6) in the gastrointestinal (GI) tract. This study presents the synthesis and anti-inflammatory evaluation of 2,4,5-trimethylpyridin-3-ol analogues, which exhibit dual inhibition of TNFα- and IL-6-induced inflammation. Analysis using in silico methods, including 3D shape-based target identification, modeling, and docking, identified G protein-coupled estrogen receptor 1 (GPER) as the molecular target for the most effective analogue, 6-26, which exhibits remarkable efficacy in ameliorating inflammation and restoring colonic mucosal integrity. This was further validated by surface plasmon resonance (SPR) assay results, which showed direct binding to GPER, and by the results showing that GPER knockdown abolished the inhibitory effects of 6-26 on TNFα and IL-6 actions. Notably, 6-26 displayed no cytotoxicity, unlike G1 and G15, a well-known GPER agonist and an antagonist, respectively, which induced necroptosis independently of GPER. These findings suggest that the GPER-selective compound 6-26 holds promise as a therapeutic candidate for IBD.

Analgesic effect of ultrasound-guided transversus abdominis plane block with or without rectus sheath block in laparoscopic cholecystectomy: a randomized, controlled trial.

BACKGROUND: Ultrasound-guided transversus abdominis plane (TAP) block is commonly used for pain control in laparoscopic cholecystectomy. However, significant pain persists, affecting patient recovery and sleep quality on the day of surgery. We compared the analgesic effect of ultrasound-guided TAP block with or without rectus sheath (RS) block in patients undergoing laparoscopic cholecystectomy using the visual analog scale (VAS) scores. METHODS: The study was registered before patient enrollment at the Clinical Research Information Service (registration number: KCT0006468, 19/08/2021). 88 American Society of Anesthesiologist physical status I-III patients undergoing laparoscopic cholecystectomy were divided into two groups. RS-TAP group received right lateral and right subcostal TAP block, and RS block with 0.2% ropivacaine (30 mL); Bi-TAP group received bilateral and right subcostal TAP block with same amount of ropivacaine. The primary outcome was visual analogue scale (VAS) for 48 h postoperatively. Secondary outcomes included the use of rescue analgesics, cumulative intravenous patient-controlled analgesia (IV-PCA) consumption, patient satisfaction, sleep quality, and incidence of adverse events. RESULTS: There was no significant difference in VAS score between two groups for 48 h postoperatively. We found no difference between the groups in any of the secondary outcomes: the use of rescue analgesics, consumption of IV-PCA, patient satisfaction with postoperative pain control, sleep quality, and the incidence of postoperative adverse events. CONCLUSION: Both RS-TAP and Bi-TAP blocks provided clinically acceptable pain control in patients undergoing laparoscopic cholecystectomy, although there was no significant difference between two combination blocks in postoperative analgesia or sleep quality.

Group A Streptococcus induces lysosomal dysfunction in THP-1 macrophages.

The human-specific bacterial pathogen group A Streptococcus (GAS) is a significant cause of morbidity and mortality. Macrophages are important to control GAS infection, but previous data indicate that GAS can persist in macrophages. In this study, we detail the molecular mechanisms by which GAS survives in THP-1 macrophages. Our fluorescence microscopy studies demonstrate that GAS is readily phagocytosed by macrophages, but persists within phagolysosomes. These phagolysosomes are not acidified, which is in agreement with our findings that GAS cannot survive in low pH environments. We find that the secreted pore-forming toxin Streptolysin O (SLO) perforates the phagolysosomal membrane, allowing leakage of not only protons but also large proteins including the lysosomal protease cathepsin B. Additionally, GAS recruits CD63/LAMP-3, which may contribute to lysosomal permeabilization, especially in the absence of SLO. Thus, although GAS does not inhibit fusion of the lysosome with the phagosome, it has multiple mechanisms to prevent proper phagolysosome function, allowing for persistence of the bacteria within the macrophage. This has important implications for not only the initial response but also the overall functionality of the macrophages, which may lead to the resulting pathologies in GAS infection. Our data suggest that therapies aimed at improving macrophage function may positively impact patient outcomes in GAS infection.

Left Upper Division Segmentectomy Compared with Lobectomy for Lung Expansion and Bronchus Tortuosity.

BACKGROUND: For patients with left upper lobe lesions, the functional benefit of left upper division segmentectomy over left upper lobectomy remains controversial. This study evaluated the clinical and functional outcomes after these two procedures. METHODS: This retrospective study included 135 patients with left upper lobe lesions (left upper lobectomy, 110; left upper division segmentectomy, 25). Propensity score matching was used to compare the two groups. Spirometry and computed tomography volume assessments were performed to evaluate bronchus angle and tortuosity. Short-term clinical respiratory symptoms were assessed via medical record reviews. RESULTS: Patients in both groups had similar preoperative characteristics, apart from tumor size (left upper division segmentectomy, 1.6 ± 0.9 cm; left upper lobectomy, 2.8 ± 1.7 cm; p = 0.002). After propensity score matching, both groups had similar preoperative spirometry and pathological results. The postoperative spirometry results were similar; however, the left upper division segmentectomy group had a significantly smaller decrease in left-side computed tomography lung volume compared with that in the left upper lobectomy group (left upper division segmentectomy, 323.6 ± 521.4 mL; left upper lobectomy, 690.7 ± 332.8 mL; p = 0.004). The left main bronchus-curvature index was higher in the left upper lobectomy group (left upper division segmentectomy, 1.074 ± 0.035; left upper lobectomy, 1.097 ± 0.036; p = 0.013), and more patients had persistent cough in the left upper lobectomy group (p = 0.001). CONCLUSIONS: Left upper division segmentectomy may be a promising option for preventing marked bronchial angulation and decreasing postoperative persistent cough in patients with left upper lobe lung cancer.

A randomized comparison of three intubation techniques/tube materials for nasotracheal intubation.

PURPOSE: We sought to compare three intubation methods using different intubation techniques/tube materials for tube advancement from the nasal cavity into the oral cavity during nasotracheal intubation. METHODS: We conducted a randomized clinical trial with adult patients scheduled to undergo elective surgery requiring nasotracheal intubation for general anesthesia. Participants were randomly allocated to a polyvinyl chloride (PVC) tube group (group P), PVC tube attached to a rubber catheter group (group PR), or velvet-soft PVC tube group (group V). Tracheal intubation was then performed based on group allocation. The primary outcome was the first-attempt success rate of tube advancement into the oral cavity; secondary outcomes included the time required for tube advancement into the oral cavity, total intubation time, and the incidence of epistaxis. RESULTS: A total of 149 patients were included in the study. The first-attempt success rate in group V (90%) was significantly higher than that in group P (58%) (odds ratio, 6.5; 95% confidence interval [CI], 2.2 to 19.2), but similar to that in group PR (100%). The mean (standard deviation) time required for tube advancement into the oral cavity was significantly shorter in group V (16 [13] sec) than in group PR [40 (10) sec; 95% CI of mean difference, 17 to 30] and group P (26 [16] sec; 95% CI of mean difference, 3 to 16). Total intubation time was longest in group PR. Epistaxis occurred the least in group V. CONCLUSIONS: Among the three intubation techniques/tube materials for nasotracheal intubation, the velvet-soft PVC tube provided the highest first-attempt success rate, most expeditious advancement into the oral cavity, and lowest incidence of epistaxis. STUDY REGISTRATION: ClinicalTrials.gov (NCT04695444); first submitted 30 December 2020.

RéSUMé: OBJECTIF: Nous avons cherché à comparer trois méthodes d'intubation utilisant différentes techniques d'intubation / matériaux de sondes pour l'avancement de la sonde de la cavité nasale dans la cavité buccale pendant l'intubation nasotrachéale. MéTHODE: Des patient·es devant recevoir une intubation nasotrachéale ont été réparti·es au hasard dans un groupe avec sondes en polychlorure de vinyle (PVC) (groupe P), un groupe avec sondes en PVC attachées à un cathéter en caoutchouc (groupe PR) ou un groupe avec sondes en PVC doux comme du velours (groupe V). L'intubation trachéale a ensuite été réalisée en fonction de l'affectation du groupe. Le critère d'évaluation principal était le taux de réussite de la première tentative d'avancement de la sonde dans la cavité buccale; les critères d'évaluation secondaires comprenaient le temps nécessaire à l'avancement de la sonde dans la cavité buccale, la durée totale de l'intubation et l'incidence d'épistaxis. RéSULTATS: Au total, 149 patient·es ont été inclus·es dans l'étude. Le taux de réussite de l'intubation à la première tentative était significativement plus élevé dans le groupe V (90 %) que dans le groupe P (58 %) (rapport de cotes, 6,5; intervalle de confiance à 95 % [IC], 2,2 à 19,2), mais similaire à celui du groupe PR (100 %). Le temps moyen (écart type) nécessaire pour l'avancement de la sonde dans la cavité buccale était significativement plus court dans le groupe V (16 [13] sec) que dans le groupe PR (40 [10] sec; IC 95 % de la différence moyenne, 17 à 30) et dans le groupe P (26 [16] sec; IC 95 % de la différence moyenne, 3 à 16). La durée totale d'intubation était la plus longue dans le groupe PR. C'est dans le groupe V que l'épistaxis a été la moins fréquente. CONCLUSION: Parmi les trois techniques d'intubation/matériaux de sonde pour l'intubation nasotrachéale, le tube en PVC doux comme du velours a fourni le taux de réussite de première tentative le plus élevé, l'avancement le plus rapide dans la cavité buccale et l'incidence d'épistaxis la plus faible. ENREGISTREMENT DE L'éTUDE: ClinicalTrials.gov (NCT04695444); première soumission le 30 décembre 2020.

A predictive model for lymph node metastasis using tumor location in presumed early-stage endometrioid endometrial cancer patients.

OBJECTIVE: The aim of this study was to identify high- and low-risk subgroups of patients with lymph node (LN) metastasis in presumed early-stage endometrioid endometrial cancer (EC) patients. METHODS: Clinicopathologic data of presumed early-stage endometrioid EC patients (n=361) treated with lymphadenectomy between March 2000 and July 2022 were analyzed. None of the patient had definite evidence of LN metastasis in a preoperative magnetic resonance imaging (MRI). A received operating characteristic curve analysis was conducted to define the sensitivity and specificity for the combined preoperative risk factors for LN metastasis, which was determined by multivariate analysis. RESULTS: Nineteen patients (5.3%) had LN metastasis. Multivariate analysis identified cervical stromal invasion on MRI (odds ratio [OR]=4.386; 95% confidence interval [CI]=1.020-18.852; p=0.047), cornual location of tumor on MRI (OR=36.208; 95% CI=7.902-165.913; p<0.001), and lower uterine segment/isthmic location of tumor on MRI (OR=8.454; 95% CI=1.567-45.610; p=0.013) as independent prognostic factors associated with LN metastasis. Patients were categorized into low- and high-risk groups according to risk criteria. Significant differences in the rates of LN metastasis were observed between the two groups (0.4% vs. 22.2%, p<0.001). CONCLUSION: Approximately 95% of presumed early-stage endometrioid EC patients did not have LN metastasis. A model using tumor location was significantly correlated with the risk of LN metastasis. Even in presumed early-stage endometrioid EC patients, therefore, tumor location should be investigated to determine whether to perform LN assessment.

Multimodal management strategies for chronic pain after spinal surgery: a comprehensive review.

"Chronic pain after spinal surgery" (CPSS) is a nonspecific term for cases in which the end result of surgery generally does not meet the preoperative expectations of the patient and surgeon. This term has replaced the previous term i.e., failed back surgery syndrome. CPSS is challenging for both patients and doctors. Despite advancements in surgical techniques and technologies, a subset of patients continue to experience persistent or recurrent pain postoperatively. This review provides an overview of the multimodal management for CPSS, ranging from conservative management to revision surgery. Drawing on recent research and clinical experience, we aimed to offer insights into the diverse strategies available to improve the quality of life of CPSS patients.

Segmentectomy quality remains important in ground-glass-dominant stage I lung cancer.

BACKGROUND: Segmentectomy for early-stage lung cancer has benefits for survival and parenchymal preservation. However, segmentectomies are technically challenging, thereby resulting in considerable variability in the quality of resection. In this study, we aimed to review the quality of segmentectomies and analyze their clinical impact. METHODS: This retrospective study reviewed patients diagnosed with stage I lung cancer after segmentectomies between 2013 and 2021. Segmentectomies were classified as anatomical or nonanatomical; anatomical resection included segmental bronchus and vessel (artery and/or vein) divisions; others were classified as nonanatomical. The primary outcome was recurrence-free and overall survival, and the secondary outcome was postoperative spirometry and lung plication, which is seen as a fibrotic line along the stapling site. RESULTS: Of the 132 segmental resections included in this study, 101 (76.5%) were anatomical segmentectomies. The median consolidation-tumor ratio was 0.40, and 83.3% (110/132) had ground-glass opacities (GGOs). Compared to nonanatomical resections, more N1 and total lymph node stations were retrieved after anatomical segmentectomies. Regarding clinical outcomes, recurrence-free survival was better after anatomical segmentectomy (p = 0.049); however, overall survival was not significantly different (p = 0.064). Furthermore, at 3-6 months postoperatively, thicker lung plication at the stapling site was observed in nonanatomical resections (p < 0.001). Subgroup analysis for complex segmentectomies revealed a larger decrease in forced-expiration volume in 1 s after nonanatomical resection. CONCLUSION: Anatomical segmentectomy resulted in better survival and a lower incidence of thick lung plication, even in GGO-dominant tumors. Therefore, further standardization and quality management of segmentectomy procedures will improve the clinical outcomes.

Impact of extended mediastinal lymph node dissection for stage I ground-glass opacity lesions.

Background: Mediastinal lymph node dissection (MLND) is a critical component in lung cancer surgery. With the increasing number of patients with ground-glass opacity (GGO) lesions, the clinical impact of MLND has not been sufficiently assessed, particularly for part-solid lesions. This study aimed to evaluate the impact of extended N2 MLND in patients with GGO lesions with a consolidation tumor ratio (CTR) of 0.3-0.7. Methods: Among patients diagnosed with stage I adenocarcinoma between 2013 and 2019, we retrospectively reviewed 138 patients with a CTR of 0.3-0.7. They were divided into the following two groups by MLND: limited N2 MLND (<3 N2 stations; n=100) and extended N2 MLND (≥3 N2 stations; n=38). Kaplan-Meier curves were used to compare oncologic outcomes and logistic regression was used to identify the predictive factors for postoperative complications (PoCs). Propensity-score matching regarding tumor characteristics and surgical extent were also performed to compare these two MLND assessments in clinical outcome. Results: The extended N2 MLND group had larger solid components (9.5 vs. 7.0 mm, P=0.002) and more patients underwent lobectomy (P=0.008). Kaplan-Meier survival curves revealed no significant difference in clinical outcomes. After propensity score matching, the difference between two MLND strategies was also non-significant in clinical outcome. However, extended N2 MLND was found to be a significant factor in the development of PoC [odds ratio (OR), 4.57; 95% confidence interval (CI): 1.26-16.6; P=0.021]. Conclusions: For GGO lesions with a CTR of 0.3-0.7, the extended MLND strategy may not be optimal in terms of clinical outcome. It could lead to more frequent early complications with no oncologic benefits. Due to the limited number of cases in this study, further prospective research on MLND for part-solid lesions is required.

Effect of local warming for arterial catheterization in adult cardiac surgery: a randomized controlled trial.

Background: The increase in internal diameter (ID) and cross-sectional area (CSA) may facilitate better arterial catheterization. Since an increase in body temperature can cause peripheral vasodilation, we aimed to determine if local warming of the radial artery (RA) catheterization site could improve the success rate of catheterization. Methods: This randomized, controlled study enrolled 160 patients aged >18 years who were scheduled for heart surgery. They were randomized into non-warming palpation (NP), non-warming ultrasonography-guided (NU), warming palpation (WP), and warming ultrasonography-guided (WU) groups. After induction, the baseline RA ultrasonography images were collected. In the warming groups (WP, WU), local warming was applied on the catheterization site. Before catheterization, the RA ultrasonography images were collected. The primary outcome was the first-attempt success rate. The secondary outcomes included the ID and CSA of the RA and overall complications. Results: Totally 152 adults were included in the analysis. The first-attempt success rates in each of the four groups were not significantly different (P=0.985). The rates in the non-warming (NP + NU) and warming (WP + WU) groups were also not different (P=0.827). Unlike non-warming group, the warming group had increased ID (3.34±0.78 vs. 3.02±0.73 mm; P<0.001) and CSA (6.9±2.8 vs. 5.8±2.4 mm2; P<0.001) compared with baseline. Conclusions: Local warming for peripheral artery catheterization does not increase the first-attempt success rate in adults undergoing cardiac surgery; however, it can increase the ID and CSA of the RA and prevent vasospasm. Trial Registration: ClinicalTrials.gov NCT04969692.

Sakurasosaponin inhibits lung cancer cell proliferation by inducing autophagy via AMPK activation.

Sakurasosaponin (S-saponin; PubChem ID: 3085160), a recently identified saponin from the roots of Primula sieboldii, has shown potential anticancer properties against various types of cancer. In the present study, the effects of S-saponin on non-small cell lung cancer (NSCLC) cell proliferation and the underlying mechanisms, were investigated. The effect of S-saponin on cell proliferation and cell death were assessed CCK-8, clonogenic assay, western blotting and Annexin V/PI double staining. S-saponin-induced autophagy was determined by confocal microscopic analysis and immunoblotting. S-saponin inhibited the proliferation of A549 and H1299 NSCLC cell lines in a dose- and time-dependent manner, without inducing apoptosis. S-saponin treatment induced autophagy in these cells, as evidenced by the increased LC3-II levels and GFP-LC3 puncta formation. It activated the adenosine monophosphate-activated protein kinase (AMPK) signaling pathway, which is crucial for autophagy induction. Inhibition of AMPK with Compound C or siRNA-mediated knockdown of AMPK abrogated S-saponin-induced autophagy and partially rescued cell proliferation. Therefore, S-saponin exerts anti-proliferative effects on NSCLC cells through autophagy induction via AMPK activation. Understanding the molecular mechanisms underlying the anticancer effects of S-saponin in NSCLC cells could provide insights for the development of novel therapeutic strategies for NSCLC.

Optimal Management of Patients with Phlegmonous Esophagitis: A Systematic Review and Meta-Analysis.

GOALS: To assess the characteristics and prognosis-influencing factors of phlegmonous esophagitis, a rare condition marked by suppurative inflammation of the esophageal submucosa and muscular layers. BACKGROUND: Effective management strategies for phlegmonous esophagitis are lacking. This study aims to systematically review cases to better understand the disease's features and prognostic determinants. METHOD: A systematic search was performed using PubMed/MEDLINE and Google Scholar from inception to 20 April 2023. Phlegmonous esophagitis case reports and studies with patient information were included; clinical manifestations, laboratory results, imaging findings, other diagnostic findings, and outcomes were analyzed. A pooled analysis was performed to investigate mortality-related risk factors. RESULTS: A total of 35 cases of phlegmonous esophagitis were selected from 31 case reports and 2 case series (median age, 57.0 years; male, 54.3%). The patients presented various clinical symptoms, with neck-to-epigastric pain and dysphagia being the most common. Comorbid diabetes mellitus was a major predisposing factor; one-third of the patients had no previous medical history. Computed tomography (CT) and endoscopic examinations were predominantly used for phlegmonous esophagitis diagnosis. Radiological findings showed that the upper and middle esophagus were most frequently involved. Treatments included administration of broad-spectrum antibiotics and drainage via endoscopy or surgery. There were three cases of mortality, and non-survivors tended to have shorter hospital stays, indicating rapid disease progression. In logistic regression, thoracic surgery was a significant mortality-related risk factor (odds ratio, 19.30; 95% confidence interval, 1.33-282.00, p = 0.03). CONCLUSION: Advancements in CT and endoscopy have led to less-invasive diagnostic and treatment methods for phlegmonous esophagitis. Endoscopic localized abscess treatment is associated with positive outcomes.

Fatty Pancreas Is a Risk Factor for Pancreatic Cancer: A Systematic Review and Meta-Analysis of 2956 Patients.

Pancreatic cancer (PC) is one of the most lethal cancers worldwide. Recently, fatty pancreas (FP) has been studied thoroughly, and although its relationship to PC is not fully understood, FP is suspected to contribute to the development of PC. We aimed to assess the association between PC and FP by conducting a systematic review and meta-analysis. We systematically searched three databases, MEDLINE, Embase, and CENTRAL, on 21 October 2022. Case-control and cross-sectional studies reporting on patients where the intra-pancreatic fat deposition was determined by modern radiology or histology were included. As main outcome parameters, FP in patients with and without PC and PC in patients with and without FP were measured. Proportion and odds ratio (OR) with a 95% confidence interval (CI) were used for effect size measure. PC among patients with FP was 32% (OR 1.32; 95% CI 0.42-4.16). However, the probability of having FP among patients with PC was more than six times higher (OR 6.13; 95% CI 2.61-14.42) than in patients without PC, whereas the proportion of FP among patients with PC was 0.62 (95% CI 0.42-0.79). Patients identified with FP are at risk of developing PC. Proper screening and follow-up of patients with FP may be recommended.

FOXJ3 Regulates Cell Proliferation and Motility Through Modulating Snail Expression in Breast Cancer Cells.

BACKGROUND/AIM: Breast cancer is the most common cancer among women and the leading cause of cancer-related deaths worldwide. Despite various therapeutic strategies, its impact on the survival rate and quality of life of patients remains limited. The Forkhead Box J3 (FOXJ3) transcription factor has been implicated in various cancers, including lung cancer, tongue squamous cell carcinoma, prostate cancer, and colorectal cancer. However, the role of FOXJ3 in breast cancer has not been elucidated. This study aimed to investigate the role of FOXJ3 in breast cancer development, migration, and invasion. MATERIALS AND METHODS: FOXJ3 expression was analyzed in patient tissues and breast cancer cell lines. Loss-of-function and gain-of-function studies were performed using MDA-MB-231 and MCF7 cell lines, respectively. Cell proliferation, migration, and invasion assays were conducted, and the effects of FOXJ3 on Snail expression were examined. RESULTS: FOXJ3 is over-expressed in breast cancer tissues compared to normal counterparts and in various breast cancer cell lines. By modulating FOXJ3 expression in breast cancer cell lines, we observed its influence on cell proliferation, migration, and invasion. Microarray analysis and subsequent validation showed that FOXJ3 modulates Snail expression, a well-known transcription factor involved in epithelial-mesenchymal transition. CONCLUSION: FOXJ3 plays a role in cell proliferation, migration, and the regulation of Snail expression and may be a potential therapeutic target for breast cancer treatment.

The Influence of Ambient Temperature on Adipose Tissue Homeostasis, Metabolic Diseases and Cancers.

Adipose tissue is a recognized energy storage organ during excessive energy intake and an endocrine and thermoregulator, which interacts with other tissues to regulate systemic metabolism. Adipose tissue dysfunction is observed in most obese mouse models and humans. However, most studies using mouse models were conducted at room temperature (RT), where mice were chronically exposed to mild cold. In this condition, energy use is prioritized for thermogenesis to maintain body temperature in mice. It also leads to the activation of the sympathetic nervous system, followed by the activation of ß-adrenergic signaling. As humans live primarily in their thermoneutral (TN) zone, RT housing for mice limits the interpretation of disease studies from mouse models to humans. Therefore, housing mice in their TN zone (~28-30 °C) can be considered to mimic humans physiologically. However, factors such as temperature ranges and TN pre-acclimatization periods should be examined to obtain reliable results. In this review, we discuss how adipose tissue responds to housing temperature and the outcomes of the TN zone in metabolic disease studies. This review highlights the critical role of TN housing in mouse models for studying adipose tissue function and human metabolic diseases.

Spillage and displacement of indocyanine green-stained tissues from uterine cervix to pelvic peritoneum: A proof of concept study for colpotomy approach in minimally invasive surgery.

OBJECTIVE: To analyze peritoneal spillage and displacement of indocyanine green (ICG)-stained tissues from uterine cervix to pelvis during intracorporeal/vaginal colpotomy in laparoscopic-assisted hysterectomy. MATERIALS AND METHODS: Eleven patients undergoing laparoscopic-assisted hysterectomy were included. One patient with an incidental diagnosis of endometrial cancer was excluded. Of the 10 patients, five underwent intracorporeal colpotomy (IC) and five received vaginal colpotomy (VC) during laparoscopic-assisted hysterectomy. Approximately 5 cm of resected round ligament from each patient was stained with ICG and cut to 1.0 × 1.0 cm in size. Four to five fragments of ICG-stained tissues were placed and sutured on the uterine cervix before colpotomy. During and after colpotomy, serial pictures under white and fluorescence light were taken to document peritoneal spillage and displacement of ICG-stained tissues to the pelvic peritoneum. RESULTS: Peritoneal spillage of ICG occurred in the entire IC group. Displacement of ICG-stained tissues from uterine cervix to pelvic peritoneum were visualized in three (60%) patients undergoing IC. In the five patients who received VC, peritoneal spillage of ICG and displacement of ICG-stained tissue to pelvic peritoneum did not occur. There were no perioperative complications. CONCLUSIONS: IC in minimally invasive radical hysterectomy should not be performed because peritoneal spillage of ICG and displacement of ICG-stained tissues from uterine cervix to pelvis frequently occurs during IC. Therefore, specific measures to prevent tumor exposure during colpotomy should be implemented in cervical cancer patients.

Non-ECG-gated high-pitch CT angiography versus hybrid ECG-gated CT angiography for aorta using 512-slice CT: comparison of image quality and radiation dose.

BACKGROUND: There have been few reports comparing image quality and radiation dose of aorta computed tomography angiography (CTA) between the high-pitch and the hybrid technique. PURPOSE: To compare the image quality and radiation dose among non-electrocardiogram (ECG)-gated high-pitch CTA and hybrid ECG-gated CTA of the aorta using 512-slice CT. MATERIAL AND METHODS: This retrospective study included 110 patients who underwent non-ECG-gated high-pitch CTA (group 1) or hybrid ECG-gated CTA (group 2) of the entire aorta. Interpretability, image noise, contrast-to-noise ratio (CNR), signal-to-noise ratio (SNR), and the mean effective radiation dose were compared. RESULTS: The mean image noise of the whole aorta was significantly lower (15.7 ± 1.8 HU vs. 16.5 ± 1.2 HU, P = 0.008) in group 1 than in group 2. The CNR (22.3 ± 4.7 vs. 20.0 ± 3.9, P < 0.001) and SNR (26.5 ± 4.9 vs. 23.2 ± 4.0, P < 0.001) were higher in group 2 compared with group 1. Neither group showed a significant difference in interpretability of the ascending aorta, cardiac chamber, aortic valve, right ostium, and left ostium (all P = 1). The mean effective radiation dose was significantly lower in group 1 than in group 2 (3.5 ± 0.9 mSv vs. 4.3 ± 0.8 mSv, P < 0.001). CONCLUSION: The non-ECG-gated high-pitch technique shows significantly improved CNR and SNR due to reduced noise with lower radiation exposure. The interpretability of the cardiac structure, ascending aorta, aortic valve, and both ostia did not differ significantly between the two groups.

Malignant Tenosynovial Giant Cell Tumor Presenting as an Extra-Articular Superficial Soft-Tissue Mass in a Knee.

Malignant tenosynovial giant cell tumor (TsGCT) is a rare disease that can arise as a recurrent lesion or co-exist with a benign TsGCT lesion. Here we report a rare case of malignant TsGCT in a 73-year-old male with a history of lymphoma. The tumor appeared as a superficial soft-tissue mass in the subcutaneous fat tissue of the left knee.

Novel peptide-based vaccine targeting heat shock protein 90 induces effective antitumor immunity in a HER2+ breast cancer murine model.

BACKGROUND: Heat shock protein 90 (HSP90) is a protein chaperone for most of the important signal transduction pathways in human epidermal growth factor receptor 2-positive (HER2+) breast cancer, including human epidermal growth factor receptor 2, estrogen receptor, progesterone receptor and Akt. The aim of our study is to identify peptide-based vaccines and to develop an effective immunotherapeutics for the treatment of HER2+ breast cancer. METHODS: HSP90-derived major histocompatibility complex (MHC) class II epitopes were selected using in silico algorithms and validated by enzyme-linked immunospot (ELISPOT). In vivo antitumor efficacy was evaluated in MMTVneu-transgenic mice. HSP90 peptide-specific systemic T-cell responses were assessed using interferon gamma ELISPOT assay, and immune microenvironment in tumors was evaluated using multiplex immunohistochemistry and TCRß sequencing. RESULTS: First, candidate HSP90-derived MHC class II epitopes with high binding affinities across multiple human HLA class II genotypes were identified using in silico algorithms. Among the top 10 peptides, p485 and p527 were selected as promising Th1 immunity-inducing epitopes with low potential for Th2 immunity induction. The selected MHC class II HSP90 peptides induced strong antigen-specific T cell responses, which was induced by cross-priming of CD8+ T cells in vivo. The HSP90 peptide vaccines were effective in the established tumor model, and their efficacy was further enhanced when combined with stimulator of interferon genes (STING) agonist and/or anticytotoxic T lymphocyte-associated antigen-4 antibody in MMTVneu-transgenic mice. Increased tumor rejection was associated with increased systemic HSP90-specific T-cell responses, increased T-cell recruitment in tumor microenvironment, intermolecular epitope spreading, and increased rearrangement of TCRß by STING agonist. CONCLUSIONS: In conclusion, we have provided the first preclinical evidence of the action mechanism of HSP90 peptide vaccines with a distinct potential for improving breast cancer treatment.

Astaxanthin Inhibits Matrix Metalloproteinase Expression by Suppressing PI3K/AKT/mTOR Activation in Helicobacter pylori-Infected Gastric Epithelial Cells.

Helicobacter pylori (H. pylori) increases production of reactive oxygen species (ROS) and activates signaling pathways associated with gastric cell invasion, which are mediated by matrix metalloproteinases (MMPs). We previously demonstrated that H. pylori activated mitogen-activated protein kinase (MAPK) and increased expression of MMP-10 in gastric epithelial cells. MMPs degrade the extracellular matrix, enhancing tumor invasion and cancer progression. The signaling pathway of phosphatidylinositol 3-kinase (PI3K)/serine/threonine protein kinase B (AKT)/mammalian target of rapamycin (mTOR) is associated with MMP expression. ROS activates PIK3/AKT/mTOR signaling in cancer. Astaxanthin, a xanthophyll carotenoid, shows antioxidant activity by reducing ROS levels in gastric epithelial cells infected with H. pylori. This study aimed to determine whether astaxanthin inhibits MMP expression, cell invasion, and migration by reducing the PI3K/AKT/mTOR signaling in H. pylori-infected gastric epithelial AGS cells. H. pylori induced PIK3/AKT/mTOR and NF-κB activation, decreased IκBα, and induced MMP (MMP-7 and -10) expression, the invasive phenotype, and migration in AGS cells. Astaxanthin suppressed these H. pylori-induced alterations in AGS cells. Specific inhibitors of PI3K, AKT, and mTOR reversed the H. pylori-stimulated NF-κB activation and decreased IκBα levels in the cells. In conclusion, astaxanthin suppressed MMP expression, cell invasion, and migration via inhibition of PI3K/AKT/mTOR/NF-κB signaling in H. pylori-stimulated gastric epithelial AGS cells.