Novel management of expected post-radiotherapy complications in hepatocellular carcinoma patients: a case report

In recent years, radiotherapy (RT) has been used to treat hepatocellular carcinoma (HCC) at each stage. This clinical trend has developed with the increasing improvement of RT techniques, which show clinical results comparable to those of other treatment modalities. Intensity-modulated radiotherapy uses a high radiation dose to improve treatment effectiveness. However, the associated radiation toxicity can damage adjacent organs. Radiation-induced gastric damage with gastric ulcers is a complication of RT. This report presents a novel management strategy for preventing post-RT gastric ulcers. We present the case of a 53-year-old male patient diagnosed with HCC, who experienced gastric ulcer after RT. Before the second round of RT, the patient was administered a gas-foaming agent, which was effective in preventing RT complications

Mechanisms of Acquired Resistance to AZD9291 A Mutation-Selective, Irreversible EGFR Inhibitor

IntroductionAZD9291, a third-generation and mutation-selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), is active against patients with EGFRT790M-mutant non–small-cell lung cancer (NSCLC) who failed prior treatment with EGFR TKIs. However, acquired resistance to AZD9291 is inevitable. In this study, we identified the mechanisms of acquired resistance to AZD9291 in EGFRT790M-mutant NSCLC.MethodsFour NSCLC patients with both an EGFR exon 19 deletion and the EGFRT790M mutation after developing acquired resistance to first-generation EGFR TKIs received AZD9291 at doses of 20 to 80 mg/day in a phase I trial (NCT01802632). Paired tumor samples before and after treatment were obtained to evaluate EGFR modifications, alternative pathway activation, and histologic transformation. Genetic alterations were analyzed using Sanger sequencing, fluorescence in situ hybridization, real-time polymerase chain reaction, and targeted exome sequencing.ResultsAll four patients achieved a partial response (median duration of response, 9 months [range, 9–11 months]) and subsequently showed resistance to AZD9291. EGFRT790M-mutant clones depopulated AZD9291-resistant tumors to below 1% (baseline, 14%–36%) in three patients with progression: one with the loss of EGFRLREAT747del/T790M-double mutant clones and two accompanied by transformation to small-cell carcinoma and focal fibroblast growth factor receptor 1 (FGFR1) amplification, respectively. EGFRT790M-mutant clones remained and the EGFR ligand was overexpressed in one patient with focal progression to AZD9291.ConclusionAcquired resistance mechanisms of AZD9291 in patients with EGFRT790M-mutant NSCLC who failed treatment with first-generation EGFR TKIs include the loss of EGFRT790M-mutant clones plus alternative pathway activation or histologic transformation and EGFR ligand–dependent activation

Angiographic analysis of the lateral intercostal artery perforator of the posterior intercostal artery: anatomic variation and clinical significance

PURPOSEKnowledge of the anatomic variations of the posterior intercostal artery (PICA) and its major branches is important during transthoracic procedures and surgery. We aimed to identify the anatomic features and variations of the lateral intercostal artery perforator (LICAP) of the PICA with selective PICA arteriography.METHODSWe retrospectively evaluated 353 PICAs in 75 patients with selective PICA arteriography for the following characteristics: incidence, length (as number of traversed intercostal spaces), distribution at the hemithorax (medial half vs. lateral half), and size as compared to the collateral intercostal artery of the PICA.RESULTSThe incidence of LICAPs was 35.9% (127/353). LICAPs were most commonly observed in the right 8th–11th intercostal spaces (33%, 42/127) and in the medial half of the hemithorax (85%, 108/127). Most LICAPs were as long as two (35.4%, 45/127) or three intercostal spaces (60.6%, 77/127). Compared to the collateral intercostal artery, 42.5% of LICAPs were larger (54/127), with most of these observed in the right 4th–7th intercostal spaces (48.8%, 22/54).CONCLUSIONWe propose the clinical significance of the LICAP as a potential risk factor for iatrogenic injury during posterior transthoracic intervention and thoracic surgery. For example, skin incisions must be as superficial as possible and directed vertically at the right 4th–7th intercostal spaces and the medial half of the thorax. Awareness of the anatomical variations of the LICAPs of the PICA will allow surgeons and interventional radiologists to avoid iatrogenic arterial injuries during posterior transthoracic procedures and surgery

Quercetin, the active phenolic component in kiwifruit, prevents hydrogen peroxide-induced inhibition of gap-junction intercellular communication

We evaluated the effects of the two main kiwifruit cultivars (gold kiwifruit (GOK) and green kiwifruit (GRK)) and their active phenolic compound, quercetin, on H2O2-induced inhibition of gap-junction intercellular communication (GJIC) in WB-F344 rat liver epithelial cells. We found that both GOK and GRK protect WB-F344 cells from H2O2-induced inhibition of GJIC. The extracellular signal-regulated protein kinase 1/2 (ERK1/2)-connexin 43 (Cx43) signalling pathway is crucial for the regulation of GJIC, and both GOK and GRK blocked the H2O2-induced phosphorylation of Cx43 and ERK1/2 in WB-F344 cells. Quercetin alone attenuated the H2O2-mediated ERK1/2-Cx43 signalling pathway and consequently reversed H2O2-mediated inhibition of GJIC in WB-F344 cells. A free radical-scavenging assay using 1,1-diphenyl-2-picrylhydrazyl showed that the scavenging activity of quercetin was higher than that of a synthetic antioxidant, butylated hydroxytoluene, per mol, suggesting that the chemopreventive effect of quercetin on H2O2-mediated inhibition of ERK1/2-Cx43 signalling and GJIC may be mediated through its free radical-scavenging activity. Since the carcinogenicity of reactive oxygen species such as H2O2 is attributable to the inhibition of GJIC, GOK, GRK and quercetin may have chemopreventive potential by preventing the inhibition of GJI

Primary Osteosarcoma in Patients Older than 40 Years of Age

Among the 665 patients who registered at our hospital, we reviewed 39 cases of high grade primary osteosarcoma in patients who were older than 40 yr of age. The aim of this study was to determine if a primary osteosarcoma in older patients has different clinical features, and a poorer prognosis than in younger patients. Two evaluations were performed. In the first, an attempt was made to determine the possible prognostic factors such as gender, location, size, alkaline phosphatase, radiological findings, chemotherapy intensity, chemotherapy-induced tumor necrosis, and surgical margin. The second evaluation involved assessment of whether there were any significant clinical differences between older patients and adolescents. According to the results, a primary osteosarcoma in older patients did not reveal any significant prognostic variables. A primary osteosarcoma in older patients showed a poorer prognosis due to relatively unusual locations, common abnormal radiological findings, and a poor response to chemotherapy. Therefore, careful attention should be paid to making an accurate diagnosis and new strategies for more effective treatment, including chemotherapy, must to be developed in order to achieve long term survival in older patients with osteosarcoma

Superior Vena Cava Syndrome Caused by Encircling Soft Tissue

Superior vena cava syndrome can occur from benign conditions that might not alter life expectancy. Here we present a case of a superior vena cava (SVC) obstruction caused by soft tissue encircling the SVC, which was strongly suspected of being an unusual focal type of fibrosing mediastinitis. A 39-year-old man with no prior medical history presented with a four-week history of facial plethora, headache and dilated veins of the neck with a dark purple color change on the anterior chest wall. Radiology examinations, including venography, and computed tomography with a 3-dimensional volume-rendering image of the chest, had revealed severe narrowing of the SVC due to tiny encircling soft tissue and collateral vessels. A total occlusion of the SVC occurred as a result of a thrombus that developed within 1 day after the diagnostic SVC angiogram. The patient underwent stent deployment three days after the administration of thrombolytic therapy

Safety, tolerability of ES16001, a novel varicella zoster virus reactivation inhibitor, in healthy adults

Purpose Herpes zoster (HZ), or shingles, is a clinical syndrome resulting from the reactivation of latent varicella zoster virus (VZV) within the sensory ganglia. We evaluated the safety and tolerability of ES16001 (ethanol extract of Elaeocarpus sylvestris var. ellipticus), a novel inhibitor of varicella zoster virus reactivation in healthy adults. Method Single-center, randomized, double-blind, placebo-controlled, single and multiple ascending dose (SAD and MAD, respectively) studies were conducted in 20- to 45-year-old healthy adults without chronic disease. In the SAD study (n = 32), subjects randomly received a single oral dose of 240, 480, 960, or 1440 mg ES16001 or a placebo. In the MAD study (n = 16), subjects randomly received once daily doses of 480 or 960 mg ES16001 or a placebo for 5 days. The safety and tolerability of the drug were evaluated by monitoring participants treatment emergent adverse events (TEAEs) and vital signs, electrocardiograms (ECGs), physical examinations, and clinical laboratory tests. Results In the SAD study, 11 adverse reactions were seen in 5 subjects, and in the MAD study, 8 adverse reactions were seen in 6 subjects. All adverse reactions were mild, and no serious adverse reactions occurred. The most common adverse reaction was an increase in alanine aminotransferase (ALT), but all test values were in the clinically non-significant range, and their clinical significance was judged to be small considering the fact that most of the test values returned to normal immediately after the end of drug administration. Conclusion ES16001 has good safety and tolerability when administered both once and repeatedly to healthy subjects. Further research is needed to identify any possible drug-induced hepatotoxicity, which appears infrequently. Our findings provide a rationale for further clinical investigations of ES16001 for the prevention of HZ. Trial registration: CRIS, KCT0006066. Registered 7 April 2021—Retrospectively registered, https://cris.nih.go.kr/cris/search/detailSearch.do/19071).This study was funded by Genencell Co. Ltd, Yongin, Korea

PI3K-Akt-Wnt Pathway Is Implicated in Exercise-Induced Improvement of Short-term Memory in Cerebral Palsy Rats

Purpose Maternal lipopolysaccharide (LPS) injection induces neurodevelopmental disorders, such as cerebral palsy. Exercise activates phosphatidylinositol 3-kinase (PI3K)-protein kinase B (Akt) signaling pathway that enhances neurogenesis. Wnt ligands are also implicated in the hippocampal neurogenesis and synaptic plasticity. Glycogen synthase kinase-3β (GSK-3β) is a downstream molecule of Akt, and GSK-3β is known to modulate hippocampal neurogenesis negatively. Methods Cerebral palsy was made by maternal LPS-injection. On the 5 weeks after birth, treadmill running was applied to the rat pups of the exercise groups, for 30 minutes, 5 times a week during 6 weeks. Results Treadmill running alleviated short-term memory impairments of the cerebral palsy rat pups. Hippocampal cell proliferation was increased and hippocampal apoptosis was suppressed by treadmill running in the cerebral palsy rat pups. Hippocampal phosphorylated-PI3K/PI3K ratio, phosphorylated-Akt/Akt ratio, and Wnt expression were enhanced by treadmill running in the cerebral palsy rat pups. In contrast, hippocampal phosphorylated-GSK-3β/GSK-3β ratio and β-catenin expression were suppressed by treadmill running in the cerebral palsy rat pups. Conclusions The results of this study showed that short-term memory improvement due to treadmill running in cerebral palsy occurs via activation of the PI3K-Akt-Wnt pathway