Cutaneous Adverse Effects of Amivantamab in Patients with Non-Small Cell Lung Cancer / 대한피부과학회지

Background@#The cutaneous adverse effects (AEs) of amivantamab, a novel monoclonal bispecific antibody against the epidermal growth factor receptor and mesenchymal-epithelial transcription factor, have not been investigated. @*Objective@#To analyze the type and prevalence of cutaneous AEs in patients with non-small cell lung cancer (NSCLC) treated with amivantamab. @*Methods@#A single-institution retrospective medical record review was conducted on patients with NSCLC who were treated with amivantamab between January 1, 2021, and June 30, 2023. A total of 37 patients receiving amivantamab monotherapy for NSCLC were included in this study. Demographic data (age, sex, body mass index, age at cancer diagnosis, age at amivantamab therapy initiation, and duration of amivantamab use) and the types and severity of cutaneous AEs were evaluated. @*Results@#Cutaneous AEs occurred in 59.5% of the patients. The most common AEs were maculopapular eruptions (37.8%), paronychia (24.3%), pruritus/xerosis (16.2%), acneiform eruptions (13.5%), pustulosis (5.4%), and scalp rashes (5.4%). No Grade 3 cutaneous AE, which led to the discontinuation of amivantamab therapy, was observed. @*Conclusion@#Our data describes an extensive review of cutaneous AEs caused by amivantamab. Further research with a larger patient population is necessary to reliably predict and manage cutaneous AEs associated with amivantamab.

Microcystic Adnexal Carcinoma on the Forehead Misdiagnosed as Cylindroma: A Case Report / 대한피부과학회지

Microcystic adnexal carcinoma (MAC) is a rare infiltrative cutaneous malignant tumor that presents as scar-like papules or plaques on sun-exposed skin. MAC can be misdiagnosed as a benign adnexal tumor, owing to its histopathologic similarity and slow growth rate. Nonetheless, MAC can show aggressive local invasion. Therefore, MAC should be treated with surgical excision or radiation therapy. Herein, we report the case of a 51-year-old woman with a flesh-colored plaque on her forehead. The patient was diagnosed with a benign adnexal tumor on the first punch biopsy. Notably, after a second incisional biopsy, the patient was finally diagnosed with MAC. This case demonstrates the difficulty of diagnosing MAC, suggesting that MAC should be considered for the differential diagnosis of slow-growing tumors in the head and neck and that multiple biopsies are needed when histological findings are ambiguous.

A Case of Successfully Treated Onychogryphosis: Traction Osteophyte Removal with Inverted T Incision and Fusiform Excision of Hyponychium / 대한피부과학회지

Onychogryphosis is a disorder of nail plate growth, which most commonly involves the toenails. It is characterized by opaque, yellow-brown thickening of the nail plate with associated marked convexity and elongation. Treatment for onychogryphosis can be conservative or operative depending on the cause and medical status of the patient. A 30-year-old male presented with onychogryphosis of the right and left toenails. Since the patient had shown recurrence after simple nail avulsion several years ago, the inverted T incision method and fusiform excision of the hypertrophic hyponychium were performed. No recurrence was observed during the 3-year follow-up period. Our results showed that nail avulsion combined with traction osteophyte removal is a suitable surgical method for treating onychogryphosis.

Phagocytic Roles of Glial Cells in Healthy and Diseased Brains

Glial cells are receiving much attention since they have been recognized as important regulators of many aspects of brain function and disease. Recent evidence has revealed that two different glial cells, astrocytes and microglia, control synapse elimination under normal and pathological conditions via phagocytosis. Astrocytes use the MEGF10 and MERTK phagocytic pathways, and microglia use the classical complement pathway to recognize and eliminate unwanted synapses. Notably, glial phagocytosis also contributes to the clearance of disease-specific protein aggregates, such as β-amyloid, huntingtin, and α-synuclein. Here we reivew recent findings showing that glial cells are active regulators in brain functions through phagocytosis and that changes in glial phagocytosis contribute to the pathogenesis of various neurodegenerative diseases. A better understanding of the cellular and molecular mechanisms of glial phagocytosis in healthy and diseased brains will greatly improve our current approach in treating these diseases.

Oxygen/Glucose Deprivation and Reperfusion Cause Modifications of Postsynaptic Morphology and Activity in the CA3 Area of Organotypic Hippocampal Slice Cultures

Brain ischemia leads to overstimulation of N-methyl-D-aspartate (NMDA) receptors, referred as excitotoxicity, which mediates neuronal cell death. However, less attention has been paid to changes in synaptic activity and morphology that could have an important impact on cell function and survival following ischemic insult. In this study, we investigated the effects of reperfusion after oxygen/glucose deprivation (OGD) not only upon neuronal cell death, but also on ultrastructural and biochemical characteristics of postsynaptic density (PSD) protein, in the stratum lucidum of the CA3 area in organotypic hippocampal slice cultures. After OGD/reperfusion, neurons were found to be damaged; the organelles such as mitochondria, endoplasmic reticulum, dendrites, and synaptic terminals were swollen; and the PSD became thicker and irregular. Ethanolic phosphotungstic acid staining showed that the density of PSD was significantly decreased, and the thickness and length of the PSD were significantly increased in the OGD/reperfusion group compared to the control. The levels of PSD proteins, including PSD-95, NMDA receptor 1, NMDA receptor 2B, and calcium/calmodulin-dependent protein kinase II, were significantly decreased following OGD/reperfusion. These results suggest that OGD/reperfusion induces significant modifications to PSDs in the CA3 area of organotypic hippocampal slice cultures, both morphologically and biochemically, and this may contribute to neuronal cell death and synaptic dysfunction after OGD/reperfusion.

Clinical Utility of Coronary CT Angiography with Low-dose Chest CT in the Evaluation of Patients with Atypical Chest Pain: A Preliminary Report

PURPOSE: To determine the clinical utility of coronary CT angiography (CCTA) with low-dose chest CT in the evaluation of patients with atypical chest pain. MATERIALS AND METHODS: Ninety-six patients (mean age 60.2 years; age range, 41-68 years; 70 males) were referred for CCTA with low-dose chest CT (16-slice MDCT, Siemens) for an evaluation of atypical chest pain. When significant stenoses (lumen diameter reduction > 50%) were detected on CCTA, invasive coronary angiography (CA) was performed as the standard of reference. In all patients, medical chart review or telephone contact with patients was used to evaluate the contribution of CCTA with low-dose chest CT to the final clinical diagnosis, at least 6 months after performing CCTA. RESULTS: Among 96 patients, seven patients (7%) had significant stenoses as detected on CCTA, whereas two patients (2%) had significant stenoses and five patients had insignificant stenoses or no stenosis, as detected on conventional catheter angiography. In 18 (19%) of the 89 patients without significant stenosis detected on CCTA, this protocol provided additional information that suggested or confirmed an alternate clinical diagnosis. CONCLUSION: In patients with atypical chest pain, CCTA with low-dose chest CT could help to exclude ischemic heart disease and could provide important ancillary information for the final diagnosis.

The Steroid Effect on the Blood-Ocular Barrier Change Induced by Triolein Emulsion as seen on Contrast-Enhanced MR Images

OBJECTIVE: The purpose of this study is to evaluate the effect of dexamethasone on the damaged blood-ocular barrier caused by triolein emulsion, using contrast-enhanced MR imaging. MATERIALS AND METHODS: An emulsion of 0.1-mL triolein in 20 mL of saline was infused into the carotid arteries of 32 cats, 12 cats were placed in the treatment group and 18 cats were placed in the Control group. Thirty minutes after the infusion of triolein emulsion, a set of orbital pre- and post-contrast T1-weighted MR images (T1WIs) were obtained. Infusion of 10 mg/kg dexamethasone into the ipsilateral carotid artery of each of the cats in the treatment group cats and 20 mL saline in each of the cats in the control group was given. A second set of pre- and post-contrast orbital T1WIs were obtained three hours following triolein emulsion infusion. Qualitative analysis was performed for the the anterior chamber (AC), the posterior chamber (PC), and in the vitreous humor of the ipsilateral and contralateral eyes. The signal intensity ratios of the ipsilateral eye over the contralateral eye were quantitatively evaluated in the three ocular chambers on the first and second set of T1WIs, and were then statistically compared. RESULTS: Qualitatively, the AC, the PC or the vitreous did not show immediate contrast enhancement on the first and the second set of post-contrast T1WIs. However, the AC and the PC showed delayed contrast enhancement for both groups of cats on the second pre-contrast T1WIs. No enhancement or minimally delayed enhancement was seen for the vitreous humor. Quantitatively, the signal intensity ratios in the PC of the treatment group of cats were statistically lower than the ratios of the control group of cats for the second set of T1WIs (p = 0.037). The AC and vitreous showed no statistically significant difference between the feline treatment group and control group (p > 0.05). CONCLUSION: Contrast-enhanced MR images revealed increased vascular permeability in the PC of the eye after infusion of triolein emulsion. Dexamethasone seems to decrease the breakdown of the blood-aqueous barrier in the PC.

Experimental Model for Research on the Blood-Ocular Barrier

PURPOSE: The eyeball has 2 blood-ocular barriers, i.e., the blood-retinal and blood-aqueous barriers. The purpose of this study was to evaluate if triolein emulsion could disrupt the barriers, and we wanted to suggest as an experimental model for future blood-ocular barrier studies. MATERIALS AND METHODS: The triolein emulsion was made of 0.1 ml triolein and 20 ml normal saline, and this was infused into the carotid artery of ten cats (the experimental group). As a control group, only normal saline was infused in another ten cats. Precontrast and postcontrast T1-weighted MR images were obtained at 30 minutes and 3 hours after embolization in both groups. The signal intensities were evaluated qualitatively and quantitatively in the anterior and posterior chambers and also in the vitreus fluid. Statistical analysis was performed by employing the Kruskal Wallist test, Dunn's Multiple Comparison test and the Wilcoxon signed rank test. RESULTS: In the control group, no contrast enhancement was demonstrated in the anterior or posterior chamber or in the vitreus fluid of the ipsilateral or contralateral eyeball on the 30 minutes MR images. The anterior chambers of the ipsilateral and contralateral eyeballs revealed delayed contrast enhancement on the 3 hour MR images. In the experimental group, the 30 minute-postembolization MR images were not different from those of the control group. The 30 minute-postembolization MR images demonstrated delayed contrast enhancement in the anterior chamber of the ipsilateral and contralateral eyeballs and in the posterior chamber of the ipsilateral eyeball. The delayed contrast enhancement of the posterior chamber of the ipsilateral eyeball was statistically significant (p<0.05). CONCLUSION: The present study demonstrated significant contrast enhancement in the posterior chamber with infusion of the triolein emulsion, and this can serve as a model for blood-aqueous barrier studies.

Alteration of Immunoreactivity for SNARE Proteins in the Rat Hippocampus after Middle Cerebral Artery Occlusion

Soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNARE) proteins, composed of two presynaptic membrane proteins [synaptosomal-associated protein of 25 kDa (SNAP-25) and syntaxin] and a presynaptic vesicular protein [vesicle-associated membrane protein (VAMP) ], serve as a core of exocytotic fusion machinery, which can be affected by ischemia. Synaptic protein in core region, striatum and cortex has been shown to alter after focal ischemia, however, little is known in hippocampus. Hippocampus is remote from ischemic core, but it is one of the most vulnerable regions. Using immunohistochemistry, the present study was undertaken to investigate the alteration of expression of SNAP-25, syntaxin, and VAMP in the hippocampus of rats which were subjected to middle cerebral artery occlusion (MCAO) for 2h and allowed to reperfuse. At 2 weeks of reperfusion, the SNAP-25 and syntaxin immunoreactivity was increased in the stratum oriens of the CA1 and the stratum lucidum of the CA3 in the ipsilateral hippocampus. However, VAMP immunoreactivity didn't show significant change. These results demonstrate that the level of the presynatpic plasma membrane proteins (SNAP-25 and syntaxin) in the rat hippocampus is more sensitively affected by focal ischemia than that of the synaptic vesicle protein (VAMP).

Increase of Synapsin I, Phosphosynapsin (ser-9), and GAP-43 in the Rat Hippocampus after Middle Cerebral Artery Occlusion

The loss of neurons and synaptic contacts following cerebral ischemia may lead to a synaptic plastic modification, which may contribute to the functional recovery after a brain lesion. Using synapsin I and GAP-43 as markers, we investigated the neuronal cell death and the synaptic plastic modification in the rat hippocampus of a middle cerebral artery occlusion (MCAO) model. Cresyl violet staining revealed that neuronal cell damage occurred after 2 h of MCAO, which progressed during reperfusion for 2 weeks. The immunoreactivity of synapsin I and GAP-43 was increased in the stratum lucidum in the CA3 subfield as well as in the inner and outer molecular layers of dentate gyrus in the hippocampus at reperfusion for 2 weeks. The immunoreactivity of phosphosynapsin was increased in the stratum lucidum in the CA3 subfield during reperfusion for 1 week. Our data suggest that the increase in the synapsin I and GAP-43 immunoreactivity probably mediates either the functional adaptation of the neurons through reactive synaptogenesis from the pre-existing presynaptic nerve terminals or the structural remodeling of their axonal connections in the areas with ischemic loss of target cells. Furthermore, phosphosynapsin may play some role in the synaptic plastic adaptations before or during reactive synaptogenesis after the MCAO.

Detection of Hepatocelluar Carcinoma on Triple-Phase Images of Liver Using Multi-Detector Row Helical CT

PURPOSE: To determine whether triple-phase multi-detector-row helical CT images of the liver improves the detection rate of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Forty-one patients with 103 HCCs underwent triple-phase multi-detector-row helical CT imaging of the entire liver after contrast administration. Early and late arterial phase images were obtained serially during a single breath-hold, and portal venous-phase images were then obtained. Each image set was independently assessed for the presence of HCC by two radiologists unaware of the possible presence of tumors, and for each phase the detection rate was determined. For each arterial-phase image, lesion conspicuity (attenuation of a tumor compared with that of its parenchyma) was calculated. RESULTS: For reader 1, the detection rates for the early arterial, late arterial, and portal venous phase were 81%, 77%, and 55%, respectively, and for reader 2 were 83%, 81%, and 68%, respectively (p>0.05). When triplephase imaging findings were combined, the detection rate was significantly higher than when only those of the early or late arterial, and portal venous, phase were used (p0.05). CONCLUSION: Triple-phase imaging of the liver, involving the early arterial, late arterial, and portal venous phase, and using multi-detector-row helical CT, increases the detection rate of HCC.

Liver Abscess Formation in Non-Tumorous Parenchyma after Transcatheter Arterial Chemoembolization (TACE) for the Treatment of Hepatocellular Carcinoma Associated with Pneumobilia / 대한간학회지

Transcatheter arterial chemoembolization (TACE) is widely used to treat inoperable hepatocellular carcinoma and metastatic tumor of the liver. Among the complications occurring after TACE, liver abscess formation in HCC is a fatal complication. The reported incidence of this complication ranges from 0% to 3.3%. Moreover, liver abscess formation in non-tumorous parenchyma is very rare. The pathogenic mechanism of this complication has been linked to several factors but retrograde enteric bacterial contamination of the biliary tract appears to be the most commonly implicated cause. The major risk factors of the biliary tract infection are pneumobilia, portal vein thrombosis, bilo-enteric anastomosis and biliary obstruction. We report a rare case of liver abscess formation in non-tumorous liver parenchyma after TACE for the treatment of hepatocellular carcinoma in a patient with pneumobilia.

Epidermal Growth Factor Dependent Expression of Plasminogen Activator and Plasminogen Activator Inhibitor in Rat Hepatocytes in Primary Culture

PURPOSE: In order to clarify the the role of epidermal growth factor (EGF) in the regulation of plasminogen activator (PA) and plasminogen activator inhibitor (PAI) during liver regeneration, we investigated the EGF-dependent gene expression of PA and PAI-1 in rat hepatocytes in primary culture. METHODS: Hepatocytes were isolated from rats using a two step perfusion technique and cultivated in dishes precoated with rat tail collagen. DNA synthesis of the hepatocytes by EGF treatment was measured with (3)H-thymidine incorporation. Gene expression for PAI-1, uPA and tPA was examined using Northern blot hybridization analysis. RESULTS: EGF treatment increased the (3)H-thymidine incorporation of the hepatocytes up to 36 hours and normal polygonal hepatocyte morphology was achieved simultaneously. tPA and PAI-1 mRNA were detected in the control hepatocytes. With the EGF treatment, the tPA mRNA level increased with time up to 48 hours, however the PAI-1 mRNA level rapidly increased to 1 hour and then decreased quickly to the control level. On the contrary, uPA mRNA was not detected in hepatocytes with or without treatment of EGF. The EGF-dependent induction of tPA and PAI-1 mRNA was a protein synthesis independent process. CONCLUSION: These results suggest that differential expression of tPA and PAI-1 mRNA by EGF in hepatocytes may play an important role in the regulation of liver regeneration. Among PAs, tPA seemed to be more important in EGF dependent growth or regeneration of primary hepatocytes in the rat since uPA mRNA was not induced in primary hepatocyte cultures in spite of EGF treatment.

Tissue Engineering of Vascular Prosthetic Grafts Using Autogenous Vein Cells

PURPOSE: To investigate bioartificial vessels capable of being used for vascular grafts, we studied cell-polymer constructs from venous smooth muscle cells (SMCs) and biodegradable scaffolds using the canine model. METHODS: Scaffolds constructed from 50/50 poly (D,L-Lactide-co-glycolide) (PLGA) were created with pores containing gelatin particles. Disk type scaffolds were used as templates of cell attachment and vascular tissue regeneration. SMCs were isolated from canine external jugular veins and primary SMCs cultures were produced with the explant-derived method. SMCs were seeded into the scaffolds and cultured statically for 4 weeks. The cell-polymer constructs were examined histochemically and using scanning electron microscopy. RESULTS: The SMCs obtained by the explant-derived method were confirmed with immunohistochemical staining using an anti-smooth muscle actin antibody. Four weeks after the SMCs were seeded into the scaffold, histological examination showed SMCs infiltration into the scaffold wall and scanning electron microscopy revealed the SMCs mass which resembled tissue on the scaffold surface. CONCLUSION: This is a pilot study for the constructing artificial vessels using tissue engineering. The construction of the ideal scaffold for vessel and the improvement of culture methods in vitro are the most important parts in this field.