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Purpose: We report a case of primary mucinous adenocarcinoma diagnosed in a patient presenting with a mass of the lower eyelid.Case summary: A 60-year-old man presenting with a mass on the left lower eyelid that had increased in size for 3 years was referred to our center after being diagnosed as mucinous adenocarcinoma. The mass was limited to the dermis and subcutaneous fat layer. The extent of the lesion was confirmed through frozen section examination, and tumor removal was performed. In immunohistochemistry, estrogen receptor, progesterone receptor, and cytokeratin-7 were positive, and cytokeratin-20 was negative. No metastasis was found, so it was diagnosed as primary mucinous adenocarcinoma of the eyelid. After surgery, adjuvant radiotherapy was administered to the tissues surrounding the lesion, and it did not recur during 12 months of follow-up period.Conclusions: Primary mucinous adenocarcinoma of the skin, especially of the eyelid, is rare, and it is important to differentiate it from metastatic mucinous adenocarcinoma of other organs. The authors diagnosed primary mucinous adenocarcinoma using immunohistochemistry, and we report how it was successfully treated through surgical excision and reconstruction of the eyelid.

Isatidis folium or Isatis tinctoria L. is a flowering plant of the Brassicaceae family, commonly known as woad, with an ancient and well-documented history as an indigo dye and medicinal plant. This study aimed to evaluate the anti-atopic dermatitis (AD) effects of Isatidis folium water extract (WIF) using a 2,4-dinitrochlorobenzene (DNCB)-induced AD-like mouse model and to investigate the underlying mechanism using tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ)-activated HaCaT cells. Oral administration of WIF reduced spleen weight, decreased serum IgE and TNF-α levels, reduced epidermal and dermal thickness, and inhibited eosinophil and mast cell recruitment to the dermis compared to DNCB-induced control groups. Furthermore, oral WIF administration suppressed extracellular signal-regulated kinase and p38 mitogen-activated protein kinase protein expression levels, p65 translocation from the cytoplasm to the nucleus, and mRNA expression of TNF-α, IFN-γ, interleukin (IL)-6, and IL-13 in skin lesion tissues. In HaCaT cells, WIF suppressed the production of regulated upon activation, normal T cell expressed and secreted (RANTES), thymus and activation-regulated chemokine (TARC), macrophage-derived chemokine (MDC), MCP-1, and MIP-3a, which are inflammatory cytokines and chemokines related to AD, and inhibited the mRNA expression of RANTES, TARC, and MDC in TNF-α/IFN-γ-stimulated HaCaT cells. Overall, the results revealed that WIF ameliorated AD-like skin inflammation by suppressing proinflammatory cytokine and chemokine production via nuclear factor-κB pathway inhibition, suggesting WIF as a potential candidate for AD treatment.

Objective: This study aimed to evaluate the effect of waiting time from diagnosis to initiation of definitive concurrent chemoradiation (CCRT) on overall survival in patients with cervical cancer. Methods: Patients with cervical cancer who had definitive CCRT between 2000 and 2017 were retrospectively reviewed. Time from pathological diagnosis to definitive CCRT was analyzed both as a continuous variable (per day) and as a categorical variable in 2 groups (Group 1 median, Group 2 > median). Patients with waiting time more than 60 days were excluded. Associations between waiting time, patients baseline characteristics, and survivals were analyzed using the Cox proportional-hazards model. Results: The median waiting time was 14 days (0-60). There were differences between Group 1 and Group 2 in age and type of chemotherapy. However, no significant difference was found in the FIGO stage, cell type, and the number of cycles of chemotherapy received during CCRT. Longer waiting time was associated with poorer overall survival on the Kaplan-Meir curve (Group 1 vs. Group 2, P = .042). On multivariate analysis, intervals as either a continuous variable (HR; 1. 023, 95% CI; 1.0061.040, P = .007) or a categorical variable (HR; 1.513, 95% CI; 1.0732.134, P = .018), FIGO stage, cell type, and the number of cycles of chemotherapy received during CCRT were significant independent prognostic factors for overall survival. Conclusion: Longer waiting time from pathological diagnosis to definitive CCRT was associated with worse overall survival. Our findings suggest that stakeholders in healthcare, including physicians and policymakers, should make an effort to minimize waiting time by rethinking factors involved in waiting time, such as referral time and time from decision making to treatment.

Recently, deep learning-based segmentation models have been widely applied in the ophthalmic field. This study presents the complete process of constructing an orbital computed tomography (CT) segmentation model based on U-Net. For supervised learning, a labor-intensive and time-consuming process is required. The method of labeling with super-resolution to efficiently mask the ground truth on orbital CT images is introduced. Also, the volume of interest is cropped as part of the pre-processing of the dataset. Then, after extracting the volumes of interest of the orbital structures, the model for segmenting the key structures of the orbital CT is constructed using U-Net, with sequential 2D slices that are used as inputs and two bi-directional convolutional long-term short memories for conserving the inter-slice correlations. This study primarily focuses on the segmentation of the eyeball, optic nerve, and extraocular muscles. The evaluation of the segmentation reveals the potential application of segmentation to orbital CT images using deep learning methods.

A choristoma is defined as a growth of histologically normal tissue in an abnormal location. Epibulbar osseous choristoma is the rarest type among all ocular choristoma with less than 100 cases reported. Here, we report a case of epibulbar osseous choristoma combined with dermolipoma and a literature review.A 15-year-old female patient presented with an accidentally found subconjunctival mass in her left eye. Slit lamp examination revealed a 10 × 10 mm elevated, sigmoid-shaped mass in the supratemporal quadrant of the bulbar conjunctiva. We performed a debulking excisional biopsy of the mass.The pathology confirmed osseous tissue surrounded by mature adipose tissue. At 1 week after the operation, the wound was clear and the patient was satisfied with the treatment. A systematic literature review of 14 previously published cases taken from PubMed dating back to 1987 along with ours was undertaken. The average age at presentation was 11.6 years and there was a female preponderance with 10 cases being female and the other 5 cases being male. Supratemporal conjunctiva was the most common site of presentation. There was no systemic disease associated with any of the cases. Since it is a benign tumor, it can be managed by observation, but if necessary, it can be treated by surgical removal.In pediatric subconjunctival mass, particularly located in supratemporal quadrant of bulbar conjunctiva, osseous choristoma should be considered in the differential diagnosis. Pre-operative CT scans will helpful to not also reduce complication with surgical excision but also helpful in prediction of diagnosis and prognosis.

Background It is important to continually reevaluate the risk/benefit calculus of internal mammary node irradiation (IMNI) in the era of modern systemic therapy. We aimed to investigate the effect of IMNI on survival in node-positive breast cancer treated with mastectomy and anthracycline plus taxane-based chemotherapy. Methods We analyzed 348 patients who underwent mastectomy and anthracycline plus taxane-based chemotherapy for node-positive breast cancer between January 2006 and December 2011. All patients received postoperative radiation therapy (RT) with IMNI (n = 105, 30.2%) or without IMNI (n = 243, 69.8%). The benefit of IMNI for disease-free survival (DFS) and overall survival (OS) was evaluated using multivariate analysis and inverse probability of treatment weighting (IPTW) to adjust for unbalanced covariates between the groups. Results After a median follow-up of 95 months, the 10-year locoregional recurrence-free survival rate, DFS, and OS in all patients were 94.8%, 77.4%, and 86.2%, respectively. The IPTW-adjusted hazard ratio (HR) for the association of IMNI (vs. no IMNI) with DFS and OS was 0.208 (95% confidence intervals (CI) 0.045–0.966) and 0.460 (95% CI, 0.220–0.962), respectively. In multivariate analysis, IMNI was a favorable factor for DFS (HR, 0.458; P = 0.021) and OS (HR 0.233, P = 0.018). Conclusions IMNI was associated with improved DFS and OS in node-positive patients treated with mastectomy, post-mastectomy RT, and taxane-based chemotherapy, although the rate of locoregional recurrence was low., Highlights • We evaluated the benefit of IMNI in modern era. • In taxane-based chemotherapy era, locoregional recurrence was very low (5.2%) in node-positive breast cancer. • IMNI was associated with improved survival.

Ocular hypertension is a major risk factor for glaucoma, which is characterized by the presence of ganglion cells, ganglion disease, and an irreversible reduction in the number of ganglion cells and axons. Although the anti-inflammatory and detoxifying effects of the maple tree (Acer palmatum Thunb.) leave extract are well known, it is unclear whether the extract can protect the eyes from ocular hypertension. This study was conducted to investigate whether the alcohol extract from A. palmatum Thunb. leaves (KIOM-2015E) had a protective effect on eyes in an animal model of steroid-induced ocular hypertension. We investigated whether KIOM-2015E had a therapeutic effect on ocular diseases induced by elevated intraocular pressure (IOP) by reducing IOP. Ocular hypertension was induced in 9-week-old female C57BL/6 mice weighing 23–27 g with 4 weeks of steroid injection. After 4 weeks, 1 or 2 mg/mL of KIOM-2015E was instilled in the mice three times a day for 5 weeks. IOP was measured weekly, and the eyes were lysed after drug administration to investigate the changes in the histological parameters and the levels of anti-apoptotic proteins. IOP was elevated, OPN1SW levels were decreased in the retinal tissue, and GFAP levels were increased in the mice with induced ocular hypertension. IOP was lowered in a concentration-dependent manner in the mice treated with KIOM-2015E. KIOM-2015E was confirmed to have an inhibitory effect on the histological changes on the retina, activity of glial and astrocytic cells, and cell death. Treatment with KIOM-2015E improved steroid-induced ocular hypertension. KIOM-2015E prevented retinal degeneration caused by increased ocular pressure by regulating protein levels and histological parameter expression in retina.

We determined the effects of two extracts from Acer palmatum Thumb. leaves (hot water extract KIOM-2015EW and 25% ethanol extract KIOM-2015EE) in a benzalkonium chloride (BAC)-induced dry eye mouse model. Dry eye was induced by 0.2% BAC for 2 weeks, followed by treatment three times (eye drop) or once (oral administration) daily with KIOM-2015E for 2 weeks. Treatment with both KIOM-2015EE and KIOM-2015EW resulted in a marked increase in tear volume production for the 4 days of treatment. The Lissamine Green staining score, TUNEL-positive cells, and inflammatory index were significantly decreased after 2 weeks. Topical KIOM-2015EE administration exhibited a greater improvement in decreasing the ocular surface staining scores, inflammation, dead cells, and increasing tear production in a dose-dependent manner compared with the other groups. Furthermore, KIOM-2015E significantly reduced the phosphorylation of NF-κB, which was activated in the BAC-treated cornea. Topical administration was much more effective than oral administration for KIOM-2015E and KIOM-2015EE was more effective than KIOM-2015EW. Application of KIOM-2015E resulted in clinical improvement, inhibited the inflammatory response, and alleviated signs of dry eye. These results indicate that KIOM-2015E has potential as a therapeutic agent for the clinical treatment of dry eye.

ObjectiveThis study aimed to report clinical outcomes of salvage radiotherapy for recurrent ovarian cancer and identify predictors of clinical outcomes.MethodsWe retrospectively reviewed data of patients who received salvage radiotherapy for recurrent ovarian cancer between January 2011 and June 2021. Stereotactic body radiotherapy, involved-field radiotherapy with conventional fractionation, and non-involved-field radiotherapy with conventional fractionation were included in this study. Local failure-free survival, progression-free survival, chemotherapy-free survival, and overall survival were assessed. Additionally, potential prognostic factors for survival were analyzed.ResultsA total of 79 patients were included with 114 recurrent lesions. The median follow-up was 18.3 months (range 1.7–83). The 2-year local failure-free survival, progression-free survival, chemotherapy-free survival, and overall survival rates were 80.7%, 10.6%, 21.2%, and 74.7%, respectively. Pre-radiotherapy platinum resistance (hazard ratio (HR) 3.326, pConclusionsSalvage radiotherapy for recurrent ovarian cancer resulted in local control with improved chemotherapy-free survival in carefully selected patients. Our results suggest that the consideration of pre-radiotherapy platinum resistance and pre-radiotherapy CA-125 doubling time could help with patient selection.

Isoquercitrin (IQC) is a component abundantly present in many plants and is known to have an anti-viral effect against various viruses. In this study, we demonstrate that IQC exhibits strong anti-influenza A virus infection, and its effect is closely related to the suppression of hemagglutinin (HA) and neuraminidase (NA) activities. We used green fluorescent protein-tagged Influenza A/PR/8/34 (H1N1), A/PR/8/34 (H1N1), and HBPV-VR-32 (H3N2) to evaluate the anti-IAV effect of IQC. The fluorescence microscopy and fluorescence-activated cell sorting analysis showed that IQC significantly decreases the levels of GFP expressed by IAV infection, dose-dependently. Consistent with that, IQC inhibited cytopathic effects by H1N1 or H3N2 IAV infection. Immunofluorescence analysis confirmed that IQC represses the IAV protein expression. Time-of-addition assay showed that IQC inhibits viral attachment and entry and exerts a strong virucidal effect during IAV infection. Hemagglutination assay confirmed that IQC affects IAV HA. Further, IQC potently reduced the NA activities of H1N1 and H3N2 IAV. Collectively, IQC prevents IAV infection at multi-stages via virucidal effects, inhibiting attachment, entry and viral release. Our results indicate that IQC could be developed as a potent antiviral drug to protect against influenza viral infection.

Background Excessive skeletal muscle loss during neoadjuvant concurrent chemoradiotherapy (NACRT) is significantly related to survival outcomes of oesophageal cancer. However, the conventional method for measuring skeletal muscle mass requires computed tomography (CT) images, and the calculation process is labour‐intensive. In this study, we built machine‐learning models to predict excessive skeletal muscle loss, using only body mass index data and blood laboratory test results. Methods We randomly split the data of 232 male patients treated with NACRT for oesophageal cancer into the training (70%) and test (30%) sets for 1000 iterations. The naive random over sampling method was applied to each training set to adjust for class imbalance, and we used seven different machine‐learning algorithms to predict excessive skeletal muscle loss. We used five input variables, namely, relative change percentage in body mass index, albumin, prognostic nutritional index, neutrophil‐to‐lymphocyte ratio, and platelet‐to‐lymphocyte ratio over 50 days. According to our previous study results, which used the maximal χ 2 method, 10.0% decrease of skeletal muscle index over 50 days was determined as the cut‐off value to define the excessive skeletal muscle loss. Results The five input variables were significantly different between the excessive and the non‐excessive muscle loss group (all P

Background: Morbidity and mortality as a result of influenza is an ongoing global health issue. Macrophages are part of the immune defense mechanism, as they play a role in the inflammatory response that blocks viral replication. Thuja orientalis Folium (TOF) has been prescribed traditionally as an expectorant for inflammatory airway disease. In this investigation, we have assessed the anti-viral properties of TOF water extract on the infectivity of the influenza A (H1N1) virus in RAW 264.7 macrophages.Method: We assessed the ability of GFP-tagged influenza A virus (A/PR/8/34-GFP) to infect murine macrophages. To determine the potential of antiviral activity using Fluorescence-activated cell sorting (FACS), fluorescent microscopy with green fluorescent protein (GFP)-tagged Influenza A/PR/8/34 virus. Hemagglutination inhibition assay, Western blotting, and Immunofluorescence analyses were performed to find the target protein. To investigate which stage of viral infection is associated with the TOF antiviral impact, we evaluated viral infection at three stages: attachment, entry, and virucidal in the presence of TOF.Results: FACS and immunofluorescence analyses results showed that TOF significantly inhibited viral infection and 100 μg/mL of TOF repressed that up to 98% of untreated control. Consistently, Western blot and immunofluorescence analyses against the influenza viral protein confirmed the TOF extract reduced the influenza viral protein expression in a dose-dependent manner. Time of addition and hemagglutination assays elucidated that TOF suppresses influenza A viral infection at early stages and interfere with HA protein.Conclusion: The TOF extract was thus found to exhibit inhibitory effects on influenza virus infection by inhibiting hemagglutination, blocking viral attachment and entry, and through virucidal effects. Based on our results, TOF may be a potential natural resource that could be utilized to develop an antiviral reagent.

Objective There is little evidence regarding the radiotherapy modification based on molecular subtypes in breast cancer. This study aimed to identify the risk and patterns of regional recurrence according to molecular subtype in patients with pN2 breast cancer. Methods We identified 454 patients who underwent radical surgery for breast cancer with 4–9 axillary lymph node metastases. All patients underwent axillary lymph node dissection, adjuvant chemotherapy and limited-field regional nodal irradiation. The rates and patterns of regional recurrence were compared between the following three subgroups: luminal type (estrogen receptor- and/or progesterone receptor-positive), HER2-type (estrogen receptor- and progesterone receptor-negative and HER2-positive) and triple-negative type (estrogen receptor-, progesterone receptor- and HER2-negative). Results Regional recurrence occurred in 18/454 patients (4%). The risk of regional recurrence was higher in the triple-negative (hazard ratio 7.641) and HER2-type (hazard ratio 4.032) subtypes than in the luminal subtype. The predominant pattern of regional recurrence was inside the radiotherapy field in triple-negative breast cancer and outside the radiotherapy field in HER2-type and luminal-type cancers. Conclusions In patients with pN2 breast cancer, the risk of regional recurrence was higher in the triple-negative and HER2-type than in the luminal type. In-field recurrence was predominant in triple-negative cancer, while out-field recurrence was frequent in luminal and HER2-type breast cancers.

Regulation of innate inflammation is critical for maintaining tissue homeostasis and barrier function, especially in those interfacing the external environment such as the skin and cornea. Expression of pro-inflammatory cytokines by injured tissues has been shown to exacerbate the inflammatory cascade, causing tissue damage. Interleukin 36 cytokine, a subfamily of the IL-1 superfamily, consists of three pro-inflammatory agonists IL36α, IL36β, and IL36γ and an IL36 receptor antagonist (IL36Ra). The current investigation, for the first time, reports that IL36γ is the primary isoform expressed by the corneal epithelium, which is significantly upregulated following corneal injury. The function of IL36γ on non-immune cells, in addition to innate inflammatory cells, in regulating tissue homeostasis has not been well investigated. Using a loss-of-function approach via neutralizing antibody treatment, our data demonstrate that blocking endogenously-expressed IL36γ in epithelial cells promotes rapid repithelialization in in vitro wound closure assay. Finally, by utilizing a naturally occurring antagonist IL36Ra in a well-established murine model of ocular injury, our study demonstrates that inhibition of IL36γ accelerates epithelial regeneration and suppress tissue inflammation. Given rapid wound healing is critical for re-establishing normal tissue structure and function, our investigation on the function of IL36γ provides evidence for the development of novel IL36γ-targeting strategies to promote tissue repair.

Broccoli (Brassica oleracea L. var. Italica) leaves are a byproduct of broccoli and could be used as a food source. The study aimed to evaluate the effect of broccoli leaves on influenza A virus (IAV) infection. We investigated the effect of ethanol extract of Broccoli leaves (EBL) on IAV infection using green fluorescent protein (GFP)–tagged Influenza A/PR/8/34 virus (PR8-GFP IAV). When EBL and PR8-GFP IAV were cotreated to RAW 264.7 cells, the fluorescence microscopy and fluorescence-activated cell sorting (FACS) analysis showed that EBL significantly reduced the levels of GFP expression by influenza viral infection dose-dependently. Immunofluorescence (IF) analysis confirmed that EBL decreased the expression of IAV proteins. EBL exhibited a strong inhibitory effect of IAV binding on the cells and moderate virucidal impact. Consistently, EBL potently suppressed the hemagglutination by IAV infection. These results indicate that EBL prevents IAV attachment via the inhibition of HA upon viral infection. Finally, EBL as an HA inhibitor of IAV could be used as the natural antiviral source to protect against influenza viral infection.

Background The Korean Radiation Oncology Group (KROG) 19 − 09 prospective cohort study aims to determine the effect of regional nodal irradiation on regional recurrence rates in ypN0 breast cancer patients. Dosimetric variations between radiotherapy (RT) plans of participating institutions may affect the clinical outcome of the study. We performed this study to assess inter-institutional dosimetric variations by dummy run. Methods Twelve participating institutions created RT plans for four clinical scenarios using computed tomography images of two dummy cases. Based on a reference structure set, we analyzed dose-volume histograms after collecting the RT plans. Results We found variations in dose distribution between institutions, especially in the regional nodal areas. Whole breast and regional nodal irradiation (WBI + RNI) plans had lower inter-institutional agreement and similarity for 95% isodose lines than WBI plans. Fleiss’s kappa values, which were used to measure inter-institutional agreement for the 95% isodose lines, were 0.830 and 0.767 for the large and medium breast WBI plans, respectively, and 0.731 and 0.679 for the large and medium breast WBI + RNI plans, respectively. There were outliers in minimum dose delivered to 95% of the structure (D95%) of axillary level 1 among WBI plans and in D95% of the interpectoral region and axillary level 4 among WBI + RNI plans. Conclusion We found inter-institutional and inter-case variations in radiation dose delivered to target volumes and organs at risk. As KROG 19 − 09 is a prospective cohort study, we accepted the dosimetric variation among the different institutions. Actual patient RT plan data should be collected to achieve reliable KROG 19 − 09 study results.

Background and purpose This study was conducted to evaluate the longitudinal impact of postmastectomy radiation therapy (PMRT) on persistent severe lymphedema (PSL) using arm volume measurements by an infrared optoelectronic volumetry. Materials and methods Of the patients who underwent mastectomy between 2008 and 2016, we included 330 patients with secondary arm lymphedema. Percentage of excessive volume (PEV) of the arm were serially assessed using an optoelectronic volumetry 1, 3, 6, 12, 18, 24, 36, and 48 months after the lymphedema diagnosis (Tlymh_Dx). We defined PSL as 2 or more episodes of PEV ≥ 20%. Risk factors for PSL were evaluated using stepwise regression analyses. Results Patients who received PMRT (n = 202, 61.2%) were more likely to have larger extent of axillary node dissection (AND), and frequent stage II/III lymphedema at Tlymh_Dx than those who did not receive PMRT (p Conclusion PMRT, especially RNI, was associated with a consistent increase in PEV in patients with arm lymphedema. Therefore, timely physical therapy is necessary for this patient population.