Background: s/Aims: Reported incidence of extrahepatic bile duct cancer is higher in Asians than in Western populations. Korea, in particular, is one of the countries with the highest incidence rates of extrahepatic bile duct cancer in the world. Although research and innovative therapeutic modalities for extrahepatic bile duct cancer are emerging, clinical guidelines are currently unavailable in Korea. The Korean Society of Hepato-Biliary-Pancreatic Surgery in collaboration with related societies (Korean Pancreatic and Biliary Surgery Society, Korean Society of Abdominal Radiology, Korean Society of Medical Oncology, Korean Society of Radiation Oncology, Korean Society of Pathologists, and Korean Society of Nuclear Medicine) decided to establish clinical guideline for extrahepatic bile duct cancer in June 2021. Methods: Contents of the guidelines were developed through subgroup meetings for each key question and a preliminary draft was finalized through a Clinical Guidelines Committee workshop. Results: In November 2021, the finalized draft was presented for public scrutiny during a formal hearing. Conclusions The extrahepatic guideline committee believed that this guideline could be helpful in the treatment of patients.

Purpose: Pembrolizumab is currently used to treat advanced triple-negative breast cancer (TNBC) and high-risk early TNBC with neoadjuvant chemotherapy (NAC). The tumor-infiltrating lymphocyte (TIL) level and programmed cell death ligand 1 (PDL1) status are predictors of response to NAC and immune checkpoint inhibitor treatment. We aimed to investigate whether the PD-L1 status in core needle biopsies (CNBs) could represent the whole tumor in TNBC. Materials and Methods: A total of 49 patients diagnosed with TNBC who received upfront surgery without NAC between January 2018 and March 2021 were included. The PD-L1 expression (SP142 and 22C3 clones) and TIL were evaluated in paired CNBs and resected specimens. The concordance PD-L1 status and TIL levels between CNBs and resected specimens were analyzed. Results: PD-L1 positivity was more frequently observed in resected specimens. The overall reliability of TIL level in the CNB was good [intraclass correlation coefficient (ICC)=0.847, p<0.001]. The agreements of PD-L1 status were good and fair, respectively (SP142, κ=0.503, p<0.001; 22C3, κ=0.380, p=0.010). As the core number of CNB increased, the reliability and agreement also improved, especially from five tumor cores (TIL, ICC=0.911, p<0.001; PD-L1 [22C3], κ=0.750, p=0.028). Regarding PD-L1 (SP142), no further improvement was observed with ≥5 tumor cores (κ=0.600, p=0.058). Conclusion CNBs with ≥5 tumor cores were sufficient to represent the TIL level and PD-L1 (22C3) status in TNBC.

Purpose: The favorable clinical efficacies of intramuscular injection of autologous blood in patients with atopic dermatitis (AD) and intramuscular injection of autologous serum in patients with chronic urticaria have been demonstrated by randomized clinical trials. In this study, we assessed the clinical effectiveness and safety of the intramuscular injection of autologous serum in patients with AD. Materials and Methods: In this randomized, placebo-controlled, and double-blind trial, 23 adolescent and adult patients with moderate-to-severe AD were enrolled. The patients were randomized to receive eight intramuscular injections of 5 mL of autologous serum (n=11) or saline (n=12) over 4 weeks, and were followed up until week 8. Changes in the clinical severity scores of AD assessed by SCORing Atopic Dermatitis (SCORAD), patient-reported Dermatology Life Quality Index (DLQI) score, and incidence of adverse events were assessed from baseline to week 8. Results: One patient in the treatment group and two patients in the placebo group were lost to follow-up before week 8. The intramuscular administration of autologous serum, compared with saline, decreased the SCORAD clinical severity score (-14.8% vs. 10.7%, p=0.006) and improved the DLQI score (-32.6% vs. 19.5%, p=0.01) from baseline to week 8. Serious adverse events were not observed. Conclusion Intramuscular injection of autologous serum may be effective in treating AD. Further studies are needed to evaluate the clinical usefulness of this intervention for AD (KCT0001969).

Background: /Aim: Transforming growth factor-beta (TGF-β) has a dichotomous role, functioning as a tumor suppressor and tumor promoter. TGF-β signatures, explored in mouse hepatocytes, have been reported to predict the clinical outcomes of hepatocellular carcinoma (HCC) patients; HCCs exhibiting early TGF-β signatures showed a better prognosis than those with late TGF-β signatures. The expression status of early and late TGF-β signatures remains unclear in defined lesions of human B-viral multistep hepatocarcinogenesis. Methods: The expression of TGF-β signatures, early and late responsive signatures of TGF-β were investigated and analyzed for their correlation in cirrhosis, low-grade dysplastic nodules (DNs), high-grade DNs, early HCCs and progressed HCCs (pHCCs) by real-time PCR and immunohistochemistry. Results: The expression levels of TGF-β signaling genes (TGFB1, TGFBR1, TGFBR2 and SMAD4) gradually increased with the progression of hepatocarcinogenesis, peaking in pHCCs. The expression of early responsive genes of TGF-β (GADD45B, FBP1, CYP1A2 and CYP3A4) gradually decreased, and that of the late TGF-β signatures (TWIST and SNAI1) significantly increased according to the progression of multistep hepatocarcinogenesis. Furthermore, mRNA levels of TWIST and SNAI1 were well correlated with those of stemness markers, with upregulation of TGF-β signaling, whereas FBP1 expression was inversely correlated with that of stemness markers. Conclusions The enrichment of the late responsive signatures of TGF-β with induction of stemness is considered to be involved in the progression of the late stage of multistep hepatocarcinogenesis, whereas the early responsive signatures of TGF-β are suggested to have tumor-suppressive roles in precancerous lesions of the early stage of multistep hepatocarcinogenesis.

Currently, no vaccine or established therapeutic agents are available for coronavirus disease 2019. The sharp increase in demand for personal protective equipment (PPE) necessitates an improvement in the protective efficacy of PPE. We evaluated the potential antimicrobial and antiviral effects of a surface-coating disinfectant (3-(trimethoxysilyl)propyldimethyl octadecyl ammonium chloride, Si-QAC) when applied onto PPE. Si-QAC-pre-coated PPE was artificially contaminated with either influenza virus or Salmonella. The results showed significantly reduced influenza and Salmonella titers in Si-QAC-coated PPE; these antimicrobial effects lasted 7 days. This suggests that this surface-coating disinfectant effectively reduces pathogen contamination of PPE, enabling their safe and long-term use.

Currently, no vaccine or established therapeutic agents are available for coronavirus disease 2019. The sharp increase in demand for personal protective equipment (PPE) necessitates an improvement in the protective efficacy of PPE. We evaluated the potential antimicrobial and antiviral effects of a surface-coating disinfectant (3-(trimethoxysilyl)propyldimethyl octadecyl ammonium chloride, Si-QAC) when applied onto PPE. Si-QAC-pre-coated PPE was artificially contaminated with either influenza virus or Salmonella. The results showed significantly reduced influenza and Salmonella titers in Si-QAC-coated PPE; these antimicrobial effects lasted 7 days. This suggests that this surface-coating disinfectant effectively reduces pathogen contamination of PPE, enabling their safe and long-term use.

Influenza virus infection is a zoonosis that has great socioeconomic effects worldwide. Influenza infection induces respiratory symptoms, while the influenza virus can infect brain and leave central nervous system sequelae. As children are more vulnerable to infection, they are at risk of long-term neurological effects once their brains are infected. We previously demonstrated that functional changes in hippocampal neurons were observed in mice recovered from neonatal influenza infection. In this study, we investigated changes in myelination properties that could affect neural dysfunction. Mice were infected with the influenza virus on postnatal day 5. Tissues were harvested from recovered mice 21-days post-infection. The expression levels for myelin basic protein (MBP) were determined, and immunohistochemical staining and transmission electron microscopy were performed. Real-time polymerase chain reaction and Western blot analyses showed that mRNA and protein expressions increased in the hippocampus and cerebellum of recovered mice. Increased MBP-staining signal was observed in the recovered mouse brain. By calculating the relative thickness of myelin sheath in relation to nerve fiber diameter (G-ratio) from electron photomicrographs, an increased G-ratio was observed in both the hippocampus and cerebellum of recovered mice. Influenza infection in oligodendrocyte-enriched primary brain cell cultures showed that proinflammatory cytokines may induce MBP upregulation. These results suggested that increased MBP expression could be a compensatory change related to hypomyelination, which may underlie neural dysfunction in recovered mice. In summary, the present results demonstrate that influenza infection during the neonatal period affects myelination and further induces functional changes in influenza-recovered mouse brain.
Animals ; Blotting, Western ; Brain ; Cell Culture Techniques ; Central Nervous System ; Cerebellum ; Child ; Cytokines ; Hippocampus ; Humans ; Influenza, Human ; Mice ; Microscopy, Electron, Transmission ; Myelin Basic Protein ; Myelin Sheath ; Nerve Fibers ; Neurons ; Oligodendroglia ; Orthomyxoviridae ; Real-Time Polymerase Chain Reaction ; RNA, Messenger ; Up-Regulation

PURPOSE: We aimed to evaluate the histologic and radiologic findings of vascular lesions after stereotactic radiosurgery (SRS) categorized as radiation-induced cavernous hemangioma (RICH). MATERIALS AND METHODS: Among 89 patients who underwent neurosurgery for cavernous hemangioma, eight RICHs from 7 patients and 10 de novo CHs from 10 patients were selected for histopathological and radiological comparison. RESULTS: Histologically, RICHs showed hematoma-like gross appearance. Microscopically, RICH exhibited a hematoma-like area accompanied by proliferation of thin-walled vasculature with fibrin deposits and infiltrating foamy macrophages. In contrast, CHs demonstrated localized malformed vasculature containing fresh and old clotted blood on gross examination. Typically, CHs consisted of thick, ectatic hyalinized vessels lined by endothelium under a light microscope. Magnetic resonance imaging of RICHs revealed some overlapping but distinct features with CHs, including enhancing cystic and solid components with absence or incomplete popcorn-like appearance and partial hemosiderin rims. CONCLUSION: Together with histologic and radiologic findings, RICH may result from blood-filled space after tissue destruction by SRS, accompanied with radiation-induced reactive changes rather than vascular malformation. Thus, the term "RICH" would be inappropriate, because it is more likely to be an inactive organizing hematoma rather than proliferation of malformed vasculature.
Adult ; Aged ; Brain/*pathology ; Brain Neoplasms/*pathology ; Female ; Hemangioma, Cavernous/complications/*pathology/surgery ; Hematoma/surgery ; Humans ; *Magnetic Resonance Imaging ; Male ; Middle Aged ; Radiosurgery/adverse effects ; Treatment Outcome

Anaphylaxis is a severe and life-threatening systemic reaction. Despite the extensive evaluation to determine the cause, 30%-60% of cases of anaphylaxis in adults remain idiopathic. Recently, omalizumab treatment has been postulated to treat refractory idiopathic anaphylaxis. We report a case of idiopathic anaphylaxis treated with omalizumab and investigated its pharmacological mechanism. A 66-year-old female presented to our clinic with recurrent anaphylaxis. She suffered from anaphylaxis 2-3 times a month for 6 months. She had past medical history of nonallergic bronchial asthma. History was carefully undertaken and anaphylaxis was not related to any specific foods, drugs, exercise, and insect bites. Serum specific IgE antibodies to common food allergens showed negative results. Oral provocation tests to food additives revealed to be negative. To screen systemic mastocytosis and mast cell activating syndrome, baseline tryptase level was checked, and it was within normal range. From comprehensive evaluation, she was diagnosed as having idiopathic anaphylaxis. She could not tolerate oral medications due to gastrointestinal discomfort, therefore, omalizumab treatment (150 mg, monthly) was started. After 6 months of treatment, anaphylaxis did not occur with complete remission status. To evaluate the pharmacological mechanism of omalizumab treatment, basophil histamine releasability test was performed. Histamine releasability induced by anti-IgE did not change after 6 months of treatment, while that induced by calcium inophore decreased. Omalizumab treatment can induce remission or favorable effects on idiopathic anaphylaxis, which may be derived from increased threshold of mast cell degranulation. Long-term studies in a larger cohort will be needed to confirm its efficacy.
Adult ; Aged ; Allergens ; Anaphylaxis* ; Antibodies ; Asthma ; Basophils ; Calcium ; Cohort Studies ; Female ; Food Additives ; Histamine ; Humans ; Immunoglobulin E ; Insect Bites and Stings ; Mast Cells ; Mastocytosis, Systemic ; Reference Values ; Tryptases ; Omalizumab

BACKGROUND: The Bethesda System for Reporting Thyroid Cytopathology (BSRTC) uses six diagnostic categories to standardize communication of thyroid fine-needle aspiration (FNA) interpretations between clinicians and cytopathologists. Since several studies have questioned the diagnostic accuracy of this system, we examined its accuracy in our hospital. METHODS: We calculated the incidences and malignancy rates of each diagnostic category in the BSRTC for 1,730 FNAs that were interpreted by four cytopathologists in Gangnam Severance Hospital between October 1, 2011, and December 31, 2011. RESULTS: The diagnostic incidences of categories I-VI were as follows: 13.3%, 40.6%, 9.1%, 0.4%, 19.3%, and 17.3%, respectively. Similarly, the malignancy rates of these categories were as follows: 35.3%, 5.6%, 69.0%, 50.0%, 98.7%, and 98.9%, respectively. In categories II, V, and VI, there were no statistically significant differences in the ranges of the malignancy rates among the four cytopathologists. However, there were significant differences in the ranges for categories I and III. CONCLUSIONS: Our findings suggest that institutions that use the BSRTC should regularly update their diagnostic criteria. We also propose that institutions issue an annual report of incidences and malignancy rates to help other clinicians improve the case management of patients with thyroid nodules.
Biopsy, Fine-Needle ; Case Management ; Diagnosis* ; Humans ; Incidence* ; Pathology ; Thyroid Gland* ; Thyroid Nodule