Tailored radiation dose according to margin width for patients with ductal carcinoma in situ after breast-conserving surgery.

A 2 mm resection margin is considered adequate for ductal carcinoma in situ (DCIS). We assessed the effectiveness of a tailored radiation dose for margins < 2 mm and the appropriate margin width for high-risk DCIS. We retrospectively evaluated 137 patients who received adjuvant radiotherapy after breast-conserving surgery for DCIS between 2013 and 2019. The patients were divided into three- positive, close (< 2 mm), and negative (≥ 2 mm) margin groups. Radiation dose to the tumor bed in equivalent dose in 2 Gy fractions were a median of 66.25 Gy, 61.81 Gy, and 59.75 Gy for positive, close, and negative margin groups, respectively. During a median follow-up of 58 months, the crude rates of local recurrence were 15.0%, 6.7%, and 4.6% in the positive, close, and negative margin groups, respectively. The positive margin group had a significantly lower 5-year local recurrence-free survival (LRFS) rate compared to the close and negative margin groups in propensity-weighted log-rank analysis (84.82%, 93.27%, and 93.20%, respectively; p = 0.008). The difference in 5-year LRFS between patients with the high- and non-high-grade tumors decreased as the margin width increased (80.4% vs. 100.0% for margin ≥ 2 mm, p < 0.001; 92.3% vs. 100.0% for margin ≥ 6 mm, p = 0.123). With the radiation dose tailored for margin widths, positive margins were associated with poorer local control than negative margins, whereas close margins were not. Widely clear margins (≥ 2 mm) were related to favorable local control for high-grade DCIS.

Clinical Impact of Genomic and Pathway Alterations in Stage I EGFR-Mutant Lung Adenocarcinoma.

PURPOSE: We investigated the clinical impact of genomic and pathway alterations in stage I epidermal growth factor receptor (EGFR)-mutant lung adenocarcinomas, which have a high recurrence rate despite complete surgical resection. MATERIALS AND METHODS: Out of the initial cohort of 257 patients with completely resected stage I EGFR-mutant lung adenocarcinoma, tumor samples from 105 patients were subjected to analysis using large-panel next-generation sequencing. We analyzed 11 canonical oncogenic pathways and determined the number of pathway alterations (NPA). Survival analyses were performed based on co-occurring alterations and NPA in three patient groups: all patients, patients with International Association for the Study of Lung Cancer (IASLC) pathology grade 2, and patients with recurrent tumors treated with EGFR-tyrosine kinase inhibitor (TKI). RESULTS: In the univariate analysis, pathological stage, IASLC grade, TP53 mutation, NPA, phosphoinositide 3-kinase pathway, p53 pathway, and cell cycle pathway exhibited significant associations with worse recurrence-free survival (RFS). Moreover, RPS6KB1 or EGFR amplifications were linked to a poorer RFS. Multivariate analysis revealed that pathologic stage, IASLC grade, and cell cycle pathway alteration were independent poor prognostic factors for RFS (p=0.002, p < 0.001, and p=0.006, respectively). In the grade 2 subgroup, higher NPA was independently associated with worse RFS (p=0.003). Additionally, in patients with recurrence treated with EGFR-TKIs, co-occurring TP53 mutations were linked to shorter progression-free survival (p=0.025). CONCLUSION: Genomic and pathway alterations, particularly cell cycle alterations, high NPA, and TP53 mutations, were associated with worse clinical outcomes in stage I EGFR-mutant lung adenocarcinoma. These findings may have implications for risk stratification and the development of new therapeutic strategies in early-stage EGFR-mutant lung cancer patients.

The prognostic value of a combined immune score in tumor and immune cells assessed by immunohistochemistry in triple-negative breast cancer.

BACKGROUND: This study aimed to develop a novel combined immune score (CIS)-based model assessing prognosis in triple-negative breast cancer (TNBC). METHODS: The expression of eight immune markers (PD-1, PD-L1, PD-L2, IDO, TIM3, OX40, OX40L, and H7-H2) was assessed with immunohistochemistry on the tumor cells (TCs) and immune cells (ICs) of 227 TNBC cases, respectively, and subsequently associated with selected clinicopathological parameters and survival. Data retrieved from The Cancer Genome Atlas (TCGA) were further examined to validate our findings. RESULTS: All immune markers were often expressed in TCs and ICs, except for PD-1 which was not expressed in TCs. In ICs, the expression of all immune markers was positively correlated between one another, except between PD-L1 and OX40, also TIM3 and OX40. In ICs, PD-1, PD-L1, and OX40L positive expression was associated with a longer progression-free survival (PFS; p = 0.040, p = 0.020, and p = 0.020, respectively). In TCs, OX40 positive expression was associated with a shorter PFS (p = 0.025). Subsequently, the TNBC patients were classified into high and low combined immune score groups (CIS-H and CIS-L), based on the expression levels of a selection of biomarkers in TCs (TCIS-H or TCIS-L) and ICs (ICIS-H or ICIS-L). The TCIS-H group was significantly associated with a longer PFS (p < 0.001). Furthermore, the ICIS-H group was additionally associated with a longer PFS (p < 0.001) and overall survival (OS; p = 0.001), at significant levels. In the multivariate analysis, both TCIS-H and ICIS-H groups were identified as independent predictors of favorable PFS (p = 0.012 and p = 0.001, respectively). ICIS-H was also shown to be an independent predictor of favorable OS (p = 0.003). The analysis of the mRNA expression data from TCGA also validated our findings regarding TNBC. CONCLUSION: Our novel TCIS and ICIS exhibited a significant prognostic value in TNBC. Additional research would be needed to strengthen our findings and identify the most efficient prognostic and predictive biomarkers for TNBC patients.

A new species of the genus Proutia Tutt (Lepidoptera, Psychidae) from Korea, based on morphology and DNA barcodes.

Background: The genus Proutia Tutt, 1899 (Lepidoptera, Psychidae) comprises 14 species found throughout the world. In East Asia, three species, Proutiachinensis Hättenschwiler & Chao, 1990, P.maculatella Saigusa & Sugimoto, 2014 and P.nigra Saigusa & Sugimoto, 2014, are known from Korea, Japan and China. New information: Proutiacornucervae Roh & Lee, sp. nov. is newly recognised from Korea. In addition, Bruandellaniphonica (Hori) is transferred to genus Proutia. Male and genitalia of the species are described and DNA barcodes are provided.

Effect of high-dose radiation therapy on positive margins after breast-conserving surgery for invasive breast cancer.

PURPOSE: Positive margins after breast-conserving surgery are associated with poor oncological outcomes and warrant additional surgery. This study aimed to evaluate the effectiveness of high-dose radiation therapy for positive margins by comparing local recurrence between patients with positive and negative margins. METHODS: We retrospectively evaluated 550 patients treated with adjuvant radiation therapy after breast-conserving surgery for invasive breast cancer between 2013 and 2019. The total equivalent dose in 2 Gy fractions (EQD2) to the tumor bed ranged from 65.81 to 66.25 Gy for positive margins and 59.31-61.81 Gy for negative margins. The differences in local recurrence between the positive and negative margin groups were analyzed. RESULTS: After a median follow-up of 58 months, the crude local recurrence rate was 7.3% in the positive margin group (n = 55) and 2.4% in the negative margin group (n = 495). Positive margins were associated with higher local recurrence without statistical significance in the entire cohort (p = 0.062). Among patients aged <60 years, those with positive margins had a significantly lower 5-year local recurrence-free survival rate than those with negative margins (89.16% vs. 97.57%, respectively; p = 0.005). In contrast, there was no significant difference in the 5-year local recurrence-free survival rate between patients with positive and negative margins among those aged ≥60 years (100.00% vs. 94.38%, respectively; p = 0.426). CONCLUSION: In this study, positive margins were not associated with poor local control in older patients after a high-dose boosts. Further prospective studies are needed to verify our findings.

[Epithelioid Hemangioendothelioma Presenting as a Right Paratracheal Mass: A Case Report]. / 우측기관주위의 ì¢ ê²©ë™ ì¢ ê´´ë¡œ 나타난 상피양 í˜ˆê´€ë‚´í”¼ì¢ : 증례 ë³´ê³ .

Epithelioid hemangioendothelioma (EHE) is a low-grade malignant vascular neoplasm that can occur anywhere in the body. EHE has a low annual incidence (0.38/106) and prevalence (< 1/106), and primary mediastinal EHE is exceedingly rare. We report a case of EHE in a 53-year-old female which manifested as an incidentally discovered mass in the right paratracheal region. In this report, authors describe the pathological and radiological findings of primary mediastinal EHE invading the superior vena cava in the right paratracheal area.

High expression of the phosphoinositide 3-kinase p11γ isoform can predict poor prognosis of non-small cell lung cancer.

The protein p110γ is an isoform of the catalytic subunit of class I phosphoinositide 3-kinases (PI3Ks). PI3Ks are involved in the regulation of cell survival, growth, proliferation, and migration and have been implicated in the oncogenesis of various cancers. In this study, p110γ expression in non-small cell lung cancer (NSCLC) and its association with clinicopathological factors and patient survival were evaluated. A total of 230 NSCLC tumors were immunohistochemically stained for p110γ. Of these, 174 (75.7%) and 56 (24.3%) were placed in the low and high expression groups, respectively. The positive rate of p110γ was significantly higher in adenocarcinoma than in squamous cell carcinoma (p⟨0.001). Advanced stage NSCLCs showed higher p110γ expression than those at an early stage (p=0.002). Irrespective of the histological tumor type, the patients with high p110γ expression had significantly worse overall survival than those with low p110γ expression (p=0.004). p110γ expression was an independent poor prognostic factor in the multivariate analysis. Our results suggest that p110γ may be involved in the development and progression of NSCLC, and that p110γ has promising potential as a prognostic factor or novel therapeutic target for NSCLC.

Efficacy of Dendrobium candidum polysaccharide extract as a moisturizer.

INTRODUCTION: This study investigated the role of natural polymers as moisturizers with low toxicity and biodegradability in the cosmetic and pharmaceutical industries. We isolated a polysaccharide extract from Dendrobium candidum (D. candidum) and determined its efficacy in skin hydration when used as an active cosmetic ingredient. METHODS: The molecular weight distribution of D. candidum polysaccharides was analyzed via gel permeation chromatography (GPC). We performed real-time reverse transcription PCR (RT-PCR) and western blotting assays to investigate the physiological mechanism of the polysaccharides extracted from D. candidum (PDC). Based on in vitro data, the efficacy of PDC in improving skin condition was tested on the face of 21 volunteers. RESULTS: The expression of filaggrin (FLG), caspase-14, and bleomycin hydrolase, which are the major components contributing to skin hydration, was significantly increased in the PDC-treated group. Further, the PDC upregulated the mRNA expression of occludin and claudin-1, which play a key role in epidermal barrier function. In addition, a topical application of PDC markedly increased skin hydration and improved trans-epidermal water loss (TEWL) and skin elasticity after 2 weeks. CONCLUSIONS: It is the first study reporting the efficacy of PDC-mediated FLG mechanism associated with positive skin hydration. PDC can be used as an active ingredient in moisturizers. Long-term application of PDC-based moisturizers may result in significant improvement in elasticity and barrier function.

Taxonomy of the coastal Thinobius Kiesenwetter (Coleoptera: Staphylinidae: Oxytelinae) in Korea.

A taxonomic study of the intertidal Thinobius Kiesenwetter in Korea is presented. Three species are recognized, two of which are identified as new species (Thinobius jejuensis Lee Ahn, sp. n. and Thinobius koreanus Lee Yoo, sp. n.) and Thinobius kuroshio (Sawada) is recorded for the first time in Korea. A key, descriptions, habitus photographs, and line drawings of diagnostic characters of these three species are provided to facilitate identification.

Pyoderma Gangrenosum Mimicking Wound Infection after Breast Cancer Surgery.

Postoperative pyoderma gangrenosum (PPG) is rare, and its diagnosis is often delayed because of its wound infection-mimicking course. A 53-year-old breast cancer patient who underwent breast-conserving surgery of the right breast presented with fever, leukocytosis, C-reactive protein elevation, and redness of the right breast on postoperative day (POD) 3. The breast wound showed desquamation with painful ulcerative changes from POD 6, and fever was sustained under antibiotic administration. Wound irrigation was attempted; however, inflammatory skin damage progressed to involvement of the entire skin overlying the breast. With clinical suspicion of PPG, skin biopsy and systemic corticosteroid initiation were performed on POD 12. Wound damage progression ceased, and the systemic inflammation subsided. The patient underwent split-thickness skin grafting under intravenous corticosteroid administration, and the wound healed after 30 days. PPG is a rare clinical scenario. Early diagnosis is critical to avoid unnecessary treatment and aggravation of the surgical wound.

Development of a forward model for Bayesian analysis of a single crystal dispersion interferometer.

The Single Crystal Dispersion Interferometer (SCDI) is a newly developed dispersion interferometer (DI) system installed on KSTAR and has obtained the first data successfully in January 2020. Unlike conventional heterodyne DI systems, which use two nonlinear crystals, only one nonlinear crystal is used to eliminate the difficulty in overlapping the first and second harmonic beams, aligning and focusing the beams to a small aperture of the second nonlinear crystal, and resolving a problem of significant efforts to maintain the beam alignment to the second nonlinear crystal after a long beam transmission. The second nonlinear crystal is replaced by a frequency doubler, a simple electronic component. To infer a line integrated electron density with its associated uncertainty consistent with the measured data, we develop a forward model of the KSTAR SCDI that can be used as a likelihood within a Bayesian-based data analysis routine. The forward model consists of two main parts, which are an optical system and an electronics system, and it takes into account noises by modeling the mechanical vibrations and the electronic noises as Gaussian distributions, while the photon noise is modeled with a Poisson distribution. The developed forward model can be used for designing and improving the SCDI system.

The new single crystal dispersion interferometer installed on KSTAR and its first measurement.

Dispersion interferometers have been used to measure line integrated electron densities from many fusion devices. To optically suppress noise due to mechanical vibrations, a conventional dispersion interferometer typically uses two nonlinear crystals located before and after the plasma along the laser beam path. Due to the long beam path, it can be difficult to overlap the fundamental and second harmonic laser beams for a heterodyne dispersion interferometer and to focus the beams on the second nonlinear crystal located after the plasma, especially when the aperture of the nonlinear crystal is small, i.e., of the order of mm. To overcome such difficulties, a new concept of a heterodyne dispersion interferometer, a single crystal dispersion interferometer (SCDI), is developed and installed on KSTAR with the laser wavelength of 1064 nm. The concept and the optical setup of the KSTAR SCDI are discussed, as well as its first measurement during a shattered pellet injection that produces abrupt and large changes in the electron density. To demonstrate feasibility, the KSTAR SCDI measurements are also compared with those from the existing two-color interferometer.

Clinical outcomes of laparoscopic versus open surgery for repairing colonoscopic perforation: a multicenter study.

PURPOSE: We conducted this study to compare the perioperative outcomes of laparoscopic surgery (LS) vs. open surgery (OS) for repairing colonoscopic perforation, and to evaluate the possible predictors of complications. METHOD: We reviewed the medical records of patients who underwent surgical repair of colonoscopic perforation by LS or OS between January 2005 and June 2019 at six Hallym University-affiliated hospitals. Multivariable analysis was performed to identify the predictors of postoperative complications. RESULTS: Of the total 99 patients, 40 underwent OS and 59 underwent LS. The postoperative hospital stay and the time to resuming a soft diet were shorter in the LS group than in the OS group (P = 0.017 and 0.026, respectively). The complication rate and Clavien-Dindo classification were not significantly different between the two groups. Multivariable analysis revealed that an American Society of Anesthesiologists score (ASA) ≥ 3 and switching from non-operative management to surgical treatment were independently associated with complications (P = 0.025 and 0.010, respectively). CONCLUSION: LS may be a safe alternative to OS for repairing colonoscopic perforation with a shorter postoperative hospital stay and time to resuming a soft diet. Patients with an ASA score ≥ 3 and those with changes to their planned treatment should be monitored carefully to minimize their risk of complications.

Comprehensive Immuno-Molecular Profiles for Liposarcoma: Roles of Programmed Death Ligand 1, Microsatellite Instability, and PIK3CA.

BACKGROUND: Developing personalized strategies for cancer has shown good efficacies. METHODS: We assessed the molecular targets programmed death ligand 1 (PD-L1), microsatellite instability (MSI), and PIK3CA. Seventy-four patients with liposarcomas who underwent curative resection were assessed for PD-L1 expression in the tumor and tumor-infiltrating lymphocytes (TILs), mismatch repair proteins (MLH1, PMS2, MSH2, and MSH6) by immunohistochemistry, MSI using polymerase chain reaction, and PIK3CA mutation/amplification using pyrosequencing and fluorescence in situ hybridization. RESULTS: Seventeen (23%) cases were TIL+ (≥1 + expression) and associated with longer 5-year overall survival than those with TIL- tumors (84.4 vs. 60.8%, p = 0.007). Six (35.3%) PD-L1+ tumors were detected only in TIL+ cases, with none detected in tumor cells. Two well-differentiated liposarcomas showed MSI, one low and one high with concurrent loss of MLH1, MSH6, and PMS2. PIK3CA mutation was detected in 7 (9.5%) [exon 9 (n = 4) and exon 20 (n = 3)] and only 1 Q546K mutation was a PD-L1+ tumor. PIK3CA copy number gain was detected in 18 (24.4%) and was associated with TIL+ tumors (p = 0.045). CONCLUSIONS: Our comprehensive immuno-molecular panel suggests that liposarcoma should be categorized based on the molecular genomic subtype for precision medicine.

Prognostic significance of glucose-related protein 94 in colorectal cancer.

AIMS: The expression of glucose-related protein 94 (GRP94), a member of the heat shock protein 90 family, was correlated with a variety of clinicopathological factors and patient survival in a large colorectal cancer (CRC) cohort. We aimed to elucidate the role of GRP94 in the prognosis of CRC patients. METHODS: Tissue microarray blocks were generated from 709 CRC samples and immunohistochemically stained for GRP94. RESULTS: Of the 709 tumours, 164 (23.1%) and 545 (76.9%) were classified in the low and high expression groups, respectively. GRP94 expression was high in CRC cases with larger tumours (p =  0.005) and advanced pT stage (p =  0.021). GRP94 expression was higher in females than males (p =  0.024). In univariate and multivariate survival analyses, high GRP94 expression was unexpectedly associated with better overall survival in CRC patients younger than 65 years of age (p =  0.001) CONCLUSION: Our conflicting results indicate that GRP94 has the ability to switch between oncogenic and tumour-suppressive roles depending on the conditions and microenvironment of the tumour cells. Furthermore, GRP94 could be a candidate biomarker to predict better prognosis in CRC patients.

Moesin (MSN) as a Novel Proteome-Based Diagnostic Marker for Early Detection of Invasive Bladder Urothelial Carcinoma in Liquid-Based Cytology.

Bladder urothelial carcinoma (BUC) is the most lethal malignancy of the urinary tract. Treatment for the disease highly depends on the invasiveness of cancer cells. Therefore, a predictive biomarker needs to be identified for invasive BUC. In this study, we employed proteomics methods on urine liquid-based cytology (LBC) samples and a BUC cell line library to determine a novel predictive biomarker for invasive BUC. Furthermore, an in vitro three-dimensional (3D) invasion study for biological significance and diagnostic validation through immunocytochemistry (ICC) were also performed. The proteomic analysis suggested moesin (MSN) as a potential biomarker to predict the invasiveness of BUC. The in vitro 3D invasion study showed that inhibition of MSN significantly decreased invasiveness in BUC cell lines. Further validation using ICC ultimately confirmed moesin (MSN) as a potential biomarker to predict the invasiveness of BUC (p = 0.023). In conclusion, we suggest moesin as a potential diagnostic marker for early detection of BUC with invasion in LBC and as a potential therapeutic target.

Utility of Human Papillomavirus Testing for Cervical Cancer Screening in Korea.

(1) Background: Cervical cancer is one of the most common cancers in Korean women. This study was performed to discover the utility of HPV (Human Papillomavirus) testing in screening of cervical lesions and to provide the prevalence of HPV and the genotype distribution in a single center of Korea. (2) Methods: A total of 15,141 women who underwent both HPV testing and cervical cytology were enrolled in this retrospective medical record review study. (3) Results: HPV testing showed higher sensitivity than cytology for the detection of histological high-grade squamous lesions. Furthermore, the sensitivity and specificity of HPV testing varied depending on the method used. The BD Onclarity™ HPV assay had higher sensitivity (90%) than the MyHPV CHIP™ kit (all types of HPV: 82%; high-risk HPV: 76%) for high-grade squamous lesions. A combination of MyHPV CHIP™ and cytology detected 90.9% (30/33) of histological high-grade squamous lesions. A combination of BD Onclarity™ HPV assay and cytology detected 96.55% (84/87) of histological high-grade squamous lesions. In addition, HPV prevalence and genotype distribution were different depending on the HPV testing method used. (4) Conclusion: HPV testing showed higher sensitivity than cytology, but the sensitivity and specificity of HPV testing had variation depending on the method used.

Differential expression of HSP90 isoforms and their correlations with clinicopathologic factors in patients with colorectal cancer.

Heat shock protein 90 (HSP90), a molecular chaperone, plays critical roles in cellular protection against various stressful stimuli and in the regulation of cellular growth and apoptosis. HSP90 has four human isoforms; HSP90α, HSP90ß, glucose related protein 94 (GRP94), and tumor necrosis factor (TNF) receptor-associated protein 1 (TRAP1). We evaluated the differential expression of these HSP90 isoforms in colorectal cancer (CRC) and correlated their expression levels with clinicopathological factors and patient survival rates. We performed immunohistochemical staining for HSP90α, HSP90ß, GRP94, and TRAP1 in 129 CRC tumor samples and found that HSP90α expression was significantly associated with advanced pT stage (P = 0.011) and shorter recurrence-free survival (RFS) (P = 0.010), whereas GRP94 expression was correlated with low grade (P = 0.029) and better RFS (P < 0.001). HSP90ß and TRAP1 had no prognostic impact, although HSP90ß expression was positively correlated with tumor size (P = 0.008). Based on our results, HSP90α and GRP94 are potential prognostic biomarkers of CRC. In addition, the differences in expression and functional activities among four HSP90 isoforms imply that isoform selectivity should be seriously considered when HSP90 inhibitors are studied or adopted for the treatment of CRC.