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Background: Surgical margin negativity is highly related to local recurrence of breast cancer. The authors performed this study to evaluate if specimen mammography or ultrasonography can replace the frozen section procedure for surgical margins. Methods: One-hundred fifty five patients with breast cancer were included in this study. After the surgery, the frozen biopsies were assessed in more than three different directions, and all specimens were analyzed with mammography and ultrasonography. The clinicopathologic characteristics of the patients were assessed, and closest tumor margin–resection margin distance (TM–RM distance) to the tumor was compared among specimen mammography, ultrasonography, and pathology. Results: On comparing initial cases of positive and negative margins, the mean closest TM–RM distance in specimen ultrasonography and final pathologic reports was statistically different between both groups (DCIS: p < 0.001, p = 0.006; IDC: p = 0.042, p = 0.022). Conclusion: When the closest TM–RM distance is less than 1.8 mm in specimen ultrasonography, the frozen section cannot be waived because of high risk of margin positivity. However, if the closest TM–RM distance is >4 mm in specimen ultrasonography, the frozen section can be omitted carefully because of the very low risk of margin positivity.

Background After publication of the findings of the American College of Surgeons Oncology Group Z1071 trial, sentinel lymph node biopsy (SLNB) has been increasingly performed in patients with breast cancer after neoadjuvant chemotherapy (NAC). Purpose To investigate the pretreatment breast MRI and clinical-pathologic characteristics associated with failed sentinel node identification after NAC in patients with breast cancer. Materials and Methods Patients who underwent SLNB after NAC between January 2015 and January 2019 were retrospectively identified. Two radiologists independently reviewed the characteristics of axillary nodes (number, perinodal infiltration, cortical thickness, and maximal diameter) at pretreatment breast MRI. The associations of the clinical-pathologic and imaging characteristics of the axillary nodes with sentinel node identification were assessed by using the χ2 test and/or the χ2 test for trend and multivariable logistic regression with odds ratio (OR) calculation. Results A total of 276 women (mean age ± standard deviation, 48 years ± 9; range, 27-68 years) were included. Sentinel nodes were identified in 252 of the 276 patients (91%). Multivariable analysis showed that higher (stage 3 or 4) clinical T stages (OR = 5.2, P = .004 for radiologist 1; OR = 4.6, P = .01 for radiologist 2), use of a single tracer (OR = 4.3, P = .04 for radiologist 1; OR = 3.9, P = .046 for radiologist 2), a greater number (10 or more) of suspicious axillary nodes (OR = 11.5, P = .002 for radiologist 1; OR = 8.3, P = .01 for radiologist 2), and the presence of perinodal infiltration (OR = 7.0, P = .002 for radiologist 1; OR = 7.5, P = .003 for radiologist 2) were associated with failed sentinel node identification. Conclusion A greater number of suspicious axillary nodes and the presence of perinodal infiltration at pretreatment MRI, higher clinical T stages, and use of a single tracer were independently associated with failed sentinel node identification after neoadjuvant chemotherapy in patients with breast cancer. © RSNA, 2020 See also the editorial by Imbriaco in this issue.

Background: The aim of this study was to investigate the effect of Acer tegmentosum Maxim (ATM) on adipocyte differentiation in 3T3-L1 adipocyte-derived cells and anti-obesity properties in high fat diet (HFD)-induced obese rats. Methods: 3T3-L1 adipocytes and HFD-induced obese rats were treated with ATM, and its effect on gene expression was analyzed using RT-PCR and Western blotting experiments. Results: Cellular lipid contents in DMI (dexamethasone, 3-isobutyl-1-methylxanthine, and insulin mixture)-treated cells increased, while ATM treatment caused a significant reduction in lipid accumulation in differentiated 3T3-L1 cells. ATM caused inhibition of adipogenesis via down-regulation of the CCAAT/enhancer binding protein β (C/EBPβ), C/EBPα, and peroxisome proliferator-activated receptor γ (PPARγ) expressions in 3T3-L1 cells. Moreover, treatment with ATM caused a decrease in the expressions of adipocyte-specific genes, such as adipocyte fatty acid-binding protein-2 (aP2), fatty acid synthase (FAS), and lipoprotein lipase (LPL), compared with DMI-stimulated adipocytes. In addition, phosphorylation levels of protein kinase B (Akt) and its downstream substrate, glycogen synthase kinase 3β (GSK3β), were significantly decreased by ATM treatment of 3T3-L1 adipocytes. Together, these results indicated that ATM caused inhibition of both adipocyte differentiation via suppression of the C/EBP family and PPARγ expressions and the Akt signaling pathway in 3T3-L1 adipocytes. In the present study, we further investigated anti-obesity effects of ATM on HFD-induced obese rats. Rats fed with HFD demonstrated elevations in body weight gain, while the administration of ATM significantly reversed BW gains and adipose tissue weights in rats fed HFD. ATM supplementation also caused a decrease in the circulating triglyceride levels and total cholesterol levels and led to inhibition of lipid accumulation in the adipose tissues in HFD-induced obesity in rats. Furthermore, epididymal fat exhibited larger adipocytes in the HFD group, whereas the ATM-treated group was significantly smaller than that of HFD group. These results strongly demonstrate that ATM administration caused a reduction in adiposity via attenuation in adipose tissue mass and adipocyte size. Conclusion: These finding demonstrated that ATM exerted anti-obesity effects through inhibition of adipocyte differentiation and adipogenesis, leading to a decrease in BW and fat tissue mass in HFD-induced obesity in rats.

A large number of pre-clinical and developmental investigations involve experimental vertebrate animals, of which mice have emerged as a favored organism. Recognition of the differences between humans and mice is essential for assessment of the relevance of animal studies to humans. The primary purpose of this study was to gauge the conservation between human and mouse vascular smooth muscle cell (VSMC) proteins mined from an analysis of the Human Protein Atlas. Two comparison were made: a) immunohistochemistry for 16 proteins in brain, heart, esophagus, bladder, stomach, lung, kidney, and aorta enabled comparison between human and mouse of protein localization in VSMC and non-vascular SMC; and b) multi-species primary protein sequence analysis of an expanded set vascular molecules enabled comparison between VSMC sequences among vertebrate species. In total, three dimensions of diversity were uncovered. First, a significant number of factors show human/mouse differences in cellular expression; these differences occurred in both VSMC and non-vascular SMC in an organ and cell-type dependent fashion. Many markers demonstrated notable cell-to-cell and regional heterogeneity in VSMC of the aorta and non-vascular SMC of the esophagus, bladder, and stomach. Second, species specificity can arise by genetic deletions as exemplified by the human protein adipogenesis regulatory factor (ADIRF), which is not present due to a large sequence gap in mice. Third, we describe significant cross-species protein sequence divergence in selected VSMC proteins which may result in altered orthologue function. In a sample of 346 vascular molecules, 15% demonstrate incomplete vertebrate species gene conservation. Divergence of predicted human/mouse VSMC protein sequences is higher than for endothelial proteins in all species examined. In the future, each of these three cross-species differences could be neutralized using gene manipulation, resulting in improved translational potential of murine experimental models.

Protein sulfhydryl residues participate in key structural and biochemical functions. Alterations in sulfhydryl status, regulated by either reversible redox reactions or by permanent covalent capping, may be challenging to identify. To advance the detection of protein sulfhydryl groups, we describe the production of new Rabbit monoclonal antibodies that react with carbamidomethyl-cysteine (CAM-cys), a product of iodoacetamide (IAM) labeling of protein sulfhydryl residues. These antibodies bind to proteins labeled with IAM (but not N-ethylmaleimide (NEM) or acrylamide) and identify multiple protein bands when applied to Western blots of cell lysates treated with IAM. The monoclonal antibodies label a subset of CAM-cys modified peptide sequences and purified proteins (human von Willebrand Factor (gene:vWF), Jagged 1 (gene:JAG1), Laminin subunit alpha 2 (gene:LAMA2), Thrombospondin-2 (gene:TSP2), and Collagen IV (gene:COL4)) but do not recognize specific proteins such as Bovine serum albumin (gene:BSA) and human Thrombospondin-1 (gene:TSP1), Biglycan (gene:BGN) and Decorin (gene:DCN). Scanning mutants of the peptide sequence used to generate the CAM-cys antibodies elucidated residues required for context dependent reactivity. In addition to recognition of in vitro labeled proteins, the antibodies were used to identify selected sulfhydryl-containing proteins from living cells that were pulse labeled with IAM. Further development of novel CAM-cys monoclonal antibodies in conjunction with other biochemical tools may complement current methods for sulfhydryl detection within specific proteins. Moreover, CAM-cys reactive reagents may be useful when there is a need to label subpopulations of proteins.

Polyphenol profiles, physicochemical properties, antioxidant activities, and inhibitory effect of adipocyte differentiation of Houttuynia cordata fermented with Lactobacillus brevis B84 were evaluated. Six polyphenols were characterized for this plant by using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS), and the results were compared with total phenolic content by a spectrophotometric method. The total amount of the identified polyphenols was lower than that determined by the spectrophotometric method. However, the fermentation process influenced polyphenol composition such as content of vanillic acid and caffeic acid. The phytochemical profiles were evaluated by high-performance liquid chromatography with UV and electrospray ionization mass spectrometry detection (HPLC-DAD-ESI-MSn). Total sugar and reducing sugar contents decreased after fermentation. Antioxidant activities such as DPPH, ABTS, and superoxide anion radical scavenging and reducing power were evaluated to compare the beneficial effect after fermentation. Fermented H. cordata increased the lipolytic effect in 3T3-L1 adipocytes. Overall, the results indicate that the fermentation of H. cordata with L. brevis B84 produces changes of phenolic compounds, antioxidant activity, and lipolytic effect.

본 연구에서는 대학생들의 부모기대부응과 진로결정수준의 관계에서 진로수행회피목표의 매개 효과를 확인하고자 하였다. 이를 위해 전국의 대학생 343명을 대상으로 온라인 설문을 실시하였고, 수집된 자료에 대해 각 변인 간 상관분석과 구조방정식을 통한 매개효과 분석을 실시하였다. 분석 결과, 첫째, 부모기대부응은 진로결정수준을 정적으로 예측하였고, 진로수행회피목표를 부적으로 예측하였으며, 진로수행회피목표는 진로결정수준을 부적으로 예측하였다. 둘째, 구조방정식 분석 결과, 부모기대부응이 진로결정수준을 예측하는 경로에서 진로수행회피목표가 부분매개효과를 보였다. 종합하면, 한국의 대학생들은 부모의 기대에 부응하지 못할수록 진로와 관련한 수행에 있어서 회피적인 목표를 지향하게 되는데, 이에 따라 자신의 진로를 결정하기가 어려워질 수 있다. 이러한 연구 결과를 바탕으로 진로상담에서의 시사점을 논하였다.

배경 및 목적: 파킨슨병 환자는 범주유창성과제 수행 시 전환능력은 저하되지만 군집능력은 유지되는 것으로 보고된다. 범주유창성 과제와 같이 시간 제한이 있는 과제에서는 전환의 수가 많아지면 군집의 수가 적어지고 군집의 수가 많아지면 전환의 수는 적어질 수 있다. 본 연구는 파킨슨병 환자들을 대상으로 시간 제한 여부에 따라 범주유창성과제에서의 군집능력이 어떻게...

Background and purpose Speech-in-noise perception deficits have been demonstrated in patients with mild cognitive impairment (MCI). However, it remains unclear whether the impairment of speech perception varies between MCI subtypes. The purpose of this study was twofold: 1) to compare speech perception performance among MCI subgroups, and 2) to identify the cognitive domains specifically related to speech-in-noise perception. Methods We studied 46 patients with MCI and 39 hearing-threshold-matched cognitively normal elderly (CNE) subjects. Two different patient classifications were used: 1) patients with amnestic mild cognitive impairment (aMCI) (n=21) or nonamnestic mild cognitive impairment (naMCI) (n=25), and 2) patients with frontal-executive dysfunction (FED) (n=16) or without FED (n=30). All of the subjects underwent audiometric, neuropsychological, and speech perception assessments. Speech-in-noise perception was measured using sentence recognition tests in the presence of two types of background noise at four levels. Results First, as the level of background noise increased, the MCI with FED group scored lower than both the MCI without FED and CNE groups under both types of noise. Second, both the naMCI and aMCI groups scored lower than the CNE group, but there were no differences between the naMCI and aMCI groups in sentence recognition under any noise conditions. Third, significant correlations were found between sentence recognition and executive function scores both in the MCI groups and in the CNE group. Conclusions Our findings suggest that frontal-executive function is strongly related to speech-in-noise perception and that MCI patients with FED have greater deficits in speech-in-noise perception compared to other subgroups of MCI.

Plasma properties of a U-shaped internal inductively coupled plasma (ICP) source (2.3 m long) operated by superimposed dual frequency was investigated as a function of power ratio of dual frequency composed of 2/13.56 MHz and 6/13.56 MHz. For the 2.3-m long linear internal-type ICP source, the use of 13.56 MHz as the operating frequency could result in nonuniform plasma due to the standing wave effect along the antenna line. By using the superimposed dual frequency composed of low frequency (2 or 6 MHz)/high frequency (13.56 MHz) at a fixed total power, higher plasma uniformity could be observed possibly due to the decreased standing wave effect compared to that obtained by 13.56 MHz without changing the plasma density. The use of 2/13.56 MHz instead of 6/13.56 MHz exhibited higher plasma uniformity. In addition, by decreasing the capacitive coupling component by the operation at the lower RF frequency, the ion bombardment energy to the substrate was lower for the operation with the superimposed dual frequency (2 or 6/13.56 MHz) compared to that with 13.56 MHz only.

Residual stress of 10 μm thick copper (Cu) film deposited using direct current (DC) magnetron sputtering system was analyzed for various pulsed DC power conditions. It is found that the increase of pulse frequency at a fixed duty ratio of 80% from continuous wave (CW) to 100 kHz while maintaining the time average power significantly decreased the residual stress of Cu film from 21.75 MPa to 1.8 MPa. The decrease of pulse duty ratio further decreased the residual stress by showing 0.7 MPa at 60% of duty ratio and 50 kHz pulse frequency. Therefore, compared to CW power, Cu film with ~1/30 lower residual stress could be deposited by using DC pulse power. The decrease of residual stress by pulsing and by decreasing the pulse duty ratio while keeping the same time average power was related to the denser film density and smaller grain size of deposited Cu film caused by increased instant sputter power during the pulsing.

Leptin plays a pivotal role in the central control of energy balance through leptin receptors expressed on specific hypothalamic nuclei. Leptin suppresses food intake and body weight and ameliorates hyperglycemia by acting on the AgRP and POMC neurons of the arcuate nucleus. Leptin action on POMC neurons are essential for control of body weight and blood glucose levels and are known to be mediated by JAK-STAT3 and PI3K signalling pathway thus increase POMC mRNA and intrinsic excitability. The effects of leptin on AgRP neurons are not as clear although it has been reported to hyperpolarize AgRP neurons through change of K+ conductance. Using cell-attached patch and whole cell patch configuration, we directly assessed neuronal response to leptin in GFP labelled AgRP or POMC neurons in mice after 18 h of food deprivation. We found leptin has a direct effect on POMC neuron through increased intrinsic excitability and decreased inhibitory synaptic inputs. However, leptin does not have any effect on intrinsic excitability of AgRP neurons in fasted condition although food deprivation induced increase of firing frequency of AgRP neurons. In conclusion, leptin probably has a direct and acute effect on POMC neurons but not on AgRP neurons to control their excitability within feeding-regulatory neuronal circuitry.

PURPOSE To compare the characteristics of patients with surgically overcorrected intermittent exotropia treated with alternate patching. METHODS The medical records of 51 patients who underwent bilateral lateral rectus muscle recession for intermittent exotropia and required alternate patching to correct postoperative overcorrection were retrospectively reviewed. Patients with postoperative esodeviation ≥18 prism diopters (PD) were started on alternate patching on postoperative day 1, whereas those with postoperative esodeviation of 10 to 17 PD were started after 2 weeks. Postoperative esodeviation

배경 및 목적: 난청이 인지기능에 미치는 영향을 파악하기 위한 다수의 연구들이 이루어지고 있으나, 그 결과는 비교적 일관적이지 않다. 이에, 본 연구는 메타분석을 통하여 장노년층에서 청력 손실군과 정상 청력을 나타내는 대조군 간 인지능력을 비교한 문헌들을 체계적으로 분석함으로써 장노년층의 난청과 인지기능 간 관련성에 대한 종합적인 결과를 도출하고자 하였다....

The aims of this study were to examine the extent of decisional conflict in end-of-life cancer treatments and to investigate the influences and predictors of decisional conflict among family surrogates. A cross-sectional, descriptive, correlational design was applied. Data were collected from a convenience sample of 102 family members who had participated in end-of-life cancer decision-making. We enrolled participants from inpatient oncology units at a university hospital in South Korea from May 2014 to January 2016. The results indicated that many family surrogates had high levels of decisional conflict and psychological stress after end-of-life cancer decision-making. Hierarchical multiple regression analyses demonstrated that decisional conflict had significant, substantial influences on decision regret and psychological stress after controlling for demographic variables. Family surrogates who were aware of the patients' wishes about end-of-life treatments and those who had good family functioning had less decisional conflict. To relieve decisional conflict regarding end-of-life cancer treatment among family surrogates, it is necessary to encourage patients to share their end-of-life treatment wishes with family members and to consider family functioning in the end-of-life decision-making process.

This study attempted to reveal the prognostic impact of microsatellite instability-high (MSI-H) colon cancer with tumor-infiltrating immune cells (TIICs) and immune checkpoint protein expression, which are good candidates for immunotherapy. The study included 89 patients with MSI-H colon cancer who underwent curative surgery at Kyungpook National University Chilgok Hospital. The expression status of specific inhibitory receptors, such as CD274 (programmed death-ligand 1, PD-L1), PDCD1 (programmed cell death 1, PD-1), cytotoxic T-lymphocyte-associated protein 4 (CTLA4), lymphocyte-activation gene 3 (LAG3), and indolamine 2′3′-dioxygenase 1 (IDO1), was retrospectively analyzed using immunohistochemistry (IHC). Among the 89 patients, CD274, LAG3, and IDO1 expressions in TIICs were observed in 68.6% (61 cases), 13.5% (12), and 28.1% (25) of patients, respectively. Meanwhile, CD274, CTLA4, and IDO1 were expressed in tumor cells of 24.7% (22 cases), 4.5% (4), and 72.0% (64) of patients, respectively. During the median follow-up duration of 39 months, 14 (15.7%) patients experienced disease recurrence. Among the five immune checkpoint proteins, CD274, LAG3, and IDO1 expressions in TIICs were significantly associated with a better disease-free survival (DFS) in a univariate analysis (P = 0.028, 0.037, and 0.030 respectively). Moreover, co-expression of CD274, LAG3, and IDO1 in TIICs showed an even better survival for DFS (P = 0.010). In a multivariate survival analysis, CD274, LAG3, and IDO1 expressions in TIICs remained as independent prognostic factors for a better DFS. CD274, LAG3, and IDO1 expressions in TIICs showed a better prognosis for patients with MSI-H colon cancer. Thus, the potential therapeutic implications of these immune checkpoint molecules should be further investigated.

Objective: A differential diagnostic role for plasma Del-1 was proposed for early breast cancer (EBC) in our previous study. We examined tumoral Del-1 expression and analyzed its prognostic impact among patients with EBC. Methods: Del-1 mRNA expression was assessed in breast epithelial and cancer cells. Meanwhile, the tumoral expression of Del-1 was determined based on tissue microarrays and immunohistochemistry results from 440 patients. Results: While a high Del-1 mRNA expression was found in all the breast cancer cell lines, the expression was significantly higher in MDA-MB-231. Tumoral expression of Del-1 was also significantly associated with a negative expression of estrogen receptor or progesterone receptor, and low expression of Ki-67, particularly in the case of triple-negative breast cancer (TNBC) (p < 0.036). Furthermore, a correlation was found between Del-1 expression and an aggressive histological grade, nuclear mitosis, and polymorphism, suggesting a possible role in tumor progression. In the survival analysis, a worse distant disease-free survival trend was noted for the group overexpressing Del-1. Conclusion: While all the investigated breast cancer cell lines exhibited Del-1 expression, the expression rate and intensity were specifically prominent in TNBC. In addition, based on its relationship to an unfavorable histology and worse survival trend, Del-1 could act as a molecular target in TNBC patients.

Short stature with optic atrophy and Pelger-Huët anomaly (SOPH) syndrome has been known to cause optic atrophy and achromatopsia resulting from stationary cone dysfunction. This report describes foveal hypoplasia in a brother and sister with SOPH syndrome, which is associated with defects in the neuroblastoma amplified sequence (NBAS) gene. As NBAS gene may play an important role in retinal homeostasis, patients with SOPH should be monitored carefully for ocular abnormalities.

Schizophrenia (SCZ) is a common and severe mental disorder. Genetic factors likely play a role in its pathophysiology as well as in treatment response. In the present study, we investigated the effects of several single nucleotide polymorphisms (SNPs) within 9 genes involved with antipsychotic (AP) mechanisms of action. Two independent samples were recruited. The Korean sample included 176 subjects diagnosed with SCZ and 326 healthy controls, while the Italian sample included 83 subjects and 194 controls. AP response as measured by the positive and negative syndrome scale (PANSS) was the primary outcome, while the secondary outcome was the SCZ risk. Exploratory analyses were performed on (1) symptom clusters response (as measured by PANSS subscales); (2) age of onset; (3) family history; and (4) suicide history. Associations evidenced in the primary analyses did not survive to the FDR correction. Concerning SCZ risk, we partially confirmed the associations among COMT and MAPK1 genetic variants and SCZ. Finally, our exploratory analysis suggested that CHRNA7 and HTR2A genes may modulate both positive and negative symptoms responses, while PLA2G4A and SIGMAR1 may modulate respectively positive and negative symptoms responses. Moreover, GSK3B, HTR2A, PLA2G4A, and S100B variants may determine an anticipation of SCZ age of onset. Our results did not support a primary role for the genes investigated in AP response as a whole. However, our exploratory findings suggested that these genes may be involved in symptom clusters response.

The aim of this study was to review our experience with ultrasound (US)-guided localization of axillary lymph nodes using activated charcoal for the guidance of axillary surgery after neoadjuvant chemotherapy (NAC) in clinically node-positive breast cancer patients. Between April 2016 and April 2017, US-guided localization of the most suspicious axillary lymph nodes at restaging US using activated charcoal (Charcotrace™) was performed in 45 consecutive, clinically node-positive breast cancer patients who had less than two suspicious nodes after NAC and axillary surgery with sentinel node biopsy. Sentinel nodes were defined as radioactive nodes or nodes containing blue dye. The concordance between final pathological results for both the tattooed and sentinel nodes was analyzed. Sentinel node biopsy failed in five patients (11%) in whom axillary surgery was performed under the guidance of the tattooed node. The tattooed nodes were identified in the surgical field in 44 patients (98%). Of the 44 tattooed nodes, 25 (57%) were concordant with the sentinel nodes and 19 (43%) were non-sentinel nodes, including the five nodes with failed sentinel node biopsy. In the final pathological results, 18 patients (40%) had metastatic nodes. The sensitivities for detecting axillary metastasis of the sentinel node biopsy, tattooed node biopsy, and the sentinel and/or tattooed node biopsy were 61% (11/18), 67% (12/18), and 78% (14/18), respectively. US-guided localization of axillary lymph nodes using activated charcoal at restaging after NAC in clinically node-positive breast cancer patients is a useful technique to guide axillary surgery, with a high identification rate.

// Hye Jin Kim 1 , Gyu-Seog Choi 1 , Jun Seok Park 1 , Soo Yeun Park 1 , Seung Hyun Cho 2 , Soo Jung Lee 3 , Byung Woog Kang 3 and Jong Gwang Kim 3 1 Colorectal Cancer Center, Kyungpook National University Medical Center, School of Medicine, Kyungpook National University, Daegu, Korea 2 Department of Radiology, Kyungpook National University Medical Center, School of Medicine, Kyungpook National University, Daegu, Korea 3 Department of Oncology/Hematology, Kyungpook National University Medical Center, School of Medicine, Kyungpook National University, Daegu, Korea Correspondence to: Gyu-Seog Choi, email: kyuschoi@mail.knu.ac.kr Keywords: lateral pelvic lymph node dissection, locally advanced rectal cancer, preoperative chemoradiation Received: May 24, 2017 Accepted: July 29, 2017 Published: August 10, 2017 ABSTRACT Background: Although lateral pelvic lymph node (LPN) metastasis is a major cause of local recurrence in patients with rectal cancer, controversy still remains on the treatment of suspected LPN metastasis, “suspicious LPN”. We aimed to determine the optimal treatment strategies for suspicious LPN, in patients with locally advanced rectal cancer who underwent preoperative chemoradiotherapy (CRT). Materials and Methods: Of 377 patients who received preoperative CRT for rectal cancer between 2006 and 2013, 84 (22.3%) had suspicious LPNs on pretreatment MRI. Patients’ characteristics, MRI findings, operative and pathologic findings, and oncologic outcomes were analyzed retrospectively. Results: Of 84 patients with suspicious LPNs, 61 showed good response to CRT on posttreatment MRI (short-axis LPN diameter < 5 mm). Among them, 31 patients underwent TME alone (group A), and 30 underwent TME plus LPND (group B). The remaining 23 patients had persistently suspicious LPNs on post-CRT MRI and underwent TME plus LPND (group C). Pathologic LPN metastasis was confirmed in five patients (16.7%) in group B and 15 (62.5%) in group C. Local recurrence developed in 7 (22.6%), 0 (0%), and 4 (17.4%) patients in groups A, B, and C, respectively. Five patients (16.1%) in group A developed in situ LPN recurrences. The 3-year disease-free survival rates were 53.7%, 74.2%, and 46.9% in groups A, B, and C, respectively. Conclusions: Study findings suggested that LPND cannot be omitted for patients with suspicious LPNs on pretreatment MRI even with good response to CRT. Findings from pretreatment MRI should be considered to determine whether LPND is indicated.

We aimed to investigate the prognostic influence of primary tumor site on the survival of patients with breast cancer.Data of 63,388 patients with primary breast cancer from the Korean Breast Cancer Registry were analyzed. Primary tumor sites were classified into 5 groups: upper outer quadrant, lower outer quadrant, upper inner quadrant, lower inner quadrant (LIQ), and central portion. We analyzed overall survival (OS) and breast cancer-specific survival (BCSS) according to primary tumor site.Central portion and LIQ showed lower survival rates regarding both OS and BCSS compared with the other 3 quadrants (all P .05) and hazard ratios were 1.267 (95% CI, 1.180-1.360, P .001) and 1.215 (95% CI, 1.097-1.345, P .001), respectively. Although central portion showed more unfavorable clinicopathologic features, LIQ showed more favorable features than the other 3 quadrants. Primary tumor site was a significant factor in univariate and multivariate analyses for OS and BCSS (all P .001). For lymph node-negative patients, LIQ showed a worse OS than the other primary tumor sites in the subgroup with no chemotherapy (P .001), but that effect disappeared in the subgroup with chemotherapy (P = .058).LIQ showed a worse prognosis despite having more favorable clinicopathologic features than other tumor locations and it was more prominent for lymph node-negative patients who received no chemotherapy. The hypothesis of possible hidden internal mammary node metastasis could be suggested to play a key role in LIQ lesions.

The prognostic role of primary tumor surgery in women with metastatic breast cancer at diagnosis is contentious. A subset of patients who will benefit from aggressive local treatment is needed to be identified. Using a nationwide database, we developed and validated a predictive model to identify long-term survivors among patients who had undergone primary tumor surgery. A total of 150,043 patients were enrolled in the Korean Breast Cancer Registry between January 1990 and December 2014. Of these, 2332 (1.6%) presented with distant metastasis at diagnosis. Using Cox proportional hazards regression, we developed and validated a model that predicts survival in patients who undergo primary tumor surgery, based on the clinicopathological features of the primary tumor. A total of 2232 metastatic breast cancer patients were reviewed. Of these, 1541 (69.0%) patients had undergone primary tumor surgery. The 3-year survival rate was 62.6% in this subgroup. Among these patients, advanced T-stage, high-grade tumor, lymphovascular invasion, negative estrogen receptor status, high Ki-67 expression, and abnormal CA 15-3 and alkaline phosphatase levels were associated with poor survival. A prediction model was developed based on these factors, which successfully identified patients with remarkable survival (score 0–3, 3-year survival rate 87.3%). The clinical significance of the model was also validated with an independent dataset. We have developed a predictive model to identify long-term survivors among women who undergo primary tumor surgery. This model will provide guidance to patients and physicians when considering surgery as a treatment modality for metastatic breast cancer.

BackgroundPatients who have residual invasive carcinoma after the receipt of neoadjuvant chemotherapy for human epidermal growth factor receptor 2 (HER2)–negative breast cancer have poor prognoses. The benefit of adjuvant chemotherapy in these patients remains unclear. MethodsWe randomly assigned 910 patients with HER2-negative residual invasive breast cancer after neoadjuvant chemotherapy (containing anthracycline, taxane, or both) to receive standard postsurgical treatment either with capecitabine or without (control). The primary end point was disease-free survival. Secondary end points included overall survival. ResultsThe result of the prespecified interim analysis met the primary end point, so this trial was terminated early. The final analysis showed that disease-free survival was longer in the capecitabine group than in the control group (74.1% vs. 67.6% of the patients were alive and free from recurrence or second cancer at 5 years; hazard ratio for recurrence, second cancer, or death, 0.70; 95% ...

BACKGROUND A standardized classification system for breast surgery that incorporates oncoplastic techniques is needed. We classified the surgical techniques for breast cancer treatment into five groups according to the extent of surgery and reconstructive methods, i.e. conventional breast-conserving surgery, partial mastectomy with volume displacement, partial mastectomy with volume replacement, simple mastectomy and total mastectomy with immediate reconstruction. We then evaluated the oncological outcomes for each of the five groups. METHODS We analysed clinical data and 5-year oncological results from patients with breast cancer who underwent breast surgery with reconstruction between 2008 and 2013. Local recurrence, distant metastasis and overall survival were investigated. RESULTS In total, 1469 patients had 1504 breast surgeries performed with a mean follow-up of 72.40 ± 16.76 months. There were 35 cases (2.3%) of locoregional recurrence and 85 cases (5.7%) of distant metastasis, and the 5-year overall survival rate was 98.6%. No statistically significant differences were observed in local recurrence, distant metastasis or death among the five surgical technique groups (P = 0.218, 0.518 and 0.450, respectively). CONCLUSION Oncological outcomes among all patients and within each surgical technique group were excellent during the 5-year follow-up period. No significant differences in oncological results were observed among the five surgical technique groups.

Schizophrenia is a debilitating illness with a chronic impact on social function and daily living. Although various antipsychotics are available, there are still many challenges and unmet needs. Thus, many compounds with diverse mechanisms have been investigated, but all approved antipsychotics still require interactions with dopamine D2 receptors. Areas covered: We searched for investigational drugs using the key words 'dopamine' and 'schizophrenia' in American and European clinical trial registers (clinicaltrials.gov; clinicaltrialsregister.eu). Published articles were searched in PubMed, Embase, Medline, PsycINFO, Cumulative Index to Nursing and Allied Health Literature (CINAHL), the Web of Science and the Cochrane Central Register of Controlled Trials Library. Expert opinion: The prospect of developing a dopamine antagonist is hopeful. Brexpiprazole and cariprazine, which were agents listed as 'investigational dopamine antagonists,' just received FDA approval. Novel agents such as BL 1020, ITI-007, and JNJ-37822681 have solid published data available, and agents such as L-THP, Lu AF35700, S33138, and SB-773812 are under vigorous investigation. However, the expected benefits of the newly developed antagonists may not be great because they offer little enhanced efficacy for negative symptoms, cognition and functional outcomes.

Purpose Eribulin mesilate was approved for the treatment of patients with locally advanced or metastatic breast cancer (MBC), who had received at least two chemotherapeutic regimens, including anthracycline and taxane. On the other hand, the efficacy and safety information of eribulin in Korean patients is limited by the lack of clinical trials. Materials and methods In this multicenter, open-label, single-arm, phase IV study, locally advanced or MBC patients were enrolled between June 2013 and April 2014 from 14 centers in Korea. One point four mg/m2 dose of eribulin was administered on days 1 and 8 of every 21 days. The primary endpoint was the frequency and intensity of the treatment emergent adverse event. The secondary endpoint was the disease control rate, which included the rate of complete responses, partial responses, and stable disease. Results A total of 101 patients received at least one dose of eribulin and were included in the safety set. The patients received a total of 543 treatment cycles, with a median of three cycles (range, 1 to 31 cycles). The most common adverse event was neutropenia (91.1% of patients, 48.3% of cycles). The frequent non-hematological adverse events included alopecia, decrease in appetite, fatigue/asthenia, and myalgia/arthralgia. The peripheral neuropathy of any grade occurred in 27 patients (26.7%), including grade 3 in two patients. Disease control rate was 52.7% and 51.3% of patients in the full analysis set and per-protocol set, respectively. Conclusion This study demonstrated the feasible safety profile and activity of eribulin in Korean patients with MBC.

Objective This study aims to examine the personality characteristics in parricide offenders, by using the Minnesota Multiphasic Personality Inventory (MMPI) test, which is commonly used in clinical medicine. Methods A total of 73 parricide offenders with schizophrenia who were admitted to National Forensic Hospital in Gongju city between September 2014 and February 2015, and 104 comparison schizophrenia patients who had been admitted to Dankook University Hospital in Cheonan city the same hospital, completed the Korean version of the MMPI. Results The parricide offender group showed significantly higher on L, F, Hs, Hy and Pd than the comparison group. The result of the regression analysis indicated that Pd and Si significantly increased the odd ratio of the sexual offender group by 2.77 times and 0.32 times, respectively (p=0.029 and p=0.023). The offenders of parricide may have developed the following characteristics: hypochondriasis, hysteria and psychopathic deviate. Conclusion These results suggested that the psychopatholgy in the offenders of parricide might be different, compared to the control group.

Psychopathy has consistently been associated with antisocial outcomes. The three- and four-factor models have been best fitted to data relating to Korean serious offenders (N = 451), offering construct validity of the Korean Psychopathy Checklist-Revised (PCL-R). However, no study has yet tested the predictive power of the Korean PCL-R to explain two different types of antisocial outcomes: (1) risk of inmates measured by correctional officers during incarceration and (2) recidivism after release. By exploring these two forms of antisociality, here we sought to establish the predictive and construct validities of the Korean version of PCL-R. We found that the deviant lifestyle (Factor 3) performed best for predicting both antisocial forms (risk and recidivism) and that the deficits in interpersonal (Factor 1) and affective (Factor 2) abilities also uniquely predicted one subtype of risk, which suggests the three-factor model is better than the four-factor model in predictions. These findings will b...

Background Volume displacement techniques that use remnant breast tissue are useful in reconstructive procedures after partial mastectomy. The authors analyzed the oncologic results of volume displacement surgery after partial mastectomy and their associations with various clinicopathologic factors. Patients and Methods One hundred fifty-eight eligible patients with breast cancer who underwent volume displacement procedures after partial mastectomy were included in this prospective study, in which associations between clinicopathologic factors and locoregional recurrence, distant metastasis, and death were analyzed. Results During a mean follow-up of 60.8 months, locoregional recurrence occurred in 3 cases (1.9%) and distant metastasis in 4 (2.5%). According to multivariate analysis, bilaterality of breast cancer ( P = .035) and adjuvant chemotherapy ( P = .042) were associated with distant metastasis. Conclusion Volume displacement procedures after partial mastectomy have good oncologic results and are acceptable procedures for patients with breast cancer.

Background: Our previous study showed the association of AQP5 upregulation with cancer proliferation and migration in breast cancer cell lines and with unfavorable prognosis in patients with early breast cancer (EBC). In the current study, we analyzed the association of AQP5 variants or their haplotypes with AQP5 expression and their prognostic impact for survival in patients with EBC. Methods: Three AQP5 polymorphisms (rs74091166, rs3736309, and rs1964676) were selected based on the SNP database and genotyped using the Sequenom MassARRAY in 374 out of 447 patients with EBC in whom AQP5 expression had been investigated in our previous study. Results: The allele frequencies of the selected variants in the current study were similar to those from Asian data previously reported. In a univariate analysis, both rs74091166 and rs1964676 were statistically associated with survival as a dominant model of minor allele. Moreover, a multivariate survival analysis revealed that the CC genotype of rs1964676 is an independent prognostic marker of survival in EBC patients, regardless of stage, tumor subtype, and adjuvant treatment [hazard ratio = 0.399, 0.384, and 0.205; p = 0.021, 0.027, and 0.016 for disease-free survival (DFS), distant DFS, and disease-specific survival, respectively]. In particular, the CT/TT genotype of rs1964676 showed an association with strong expression of AQP5 (58.6 vs. 26.0%; p = 0.001), without any associations with clinical or pathological characteristics including tumor subtype, stage, or histologic grade. Conclusion: The current study suggests AQP5 rs1964676 as a new potential prognostic marker in patients with EBC involved in AQP5 expression.

Aim We evaluated the role of long noncoding ribonucleic acid (lncRNA) in breast cancer cell lines by quantitative reverse transcription-polymerase change reaction. Materials and methods The effects of small NF90-associated RNA (snaR) with RNA interference on proliferation, migration and invasion of MDA-MB-231 cells were observed by 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide, wound healing and transwell assay. Results Among 90 lncRNAs, E2F transcription factor 4, p107/p130-binding (E2F4) antisense, insulin-like growth factor 2 antisense (IGF2AS), snaR, and small nucleolar RNA host gene 5 (SNHG5) were up-regulated in MDA-MB-231 and 7SK, antisense noncoding RNA in the INK4 locus (ANRIL), IGF2AS, Nespas, p53 mRNA, and snaR were up-regulated in MCF-7 cells. Down-regulation of snaR inhibited the proliferation, migration, and invasion of MDA-MD-231 breast cancer cells. Conclusion LncRNA snaR was found to be up-regulated in breast cancer cells, and the cancer progression of MDA-MB-231 cells was significantly suppressed by down-regulation of snaR. Therefore, snaR knockdown has potential as a treatment modality for triple-negative breast cancer.

Purpose Neoadjuvant chemotherapy (NAC) involving trastuzumab markedly increases pathologic complete response (pCR) rates in patients with human epidermal growth factor receptor 2-positive (HER2+) breast cancer. Despite increasing pCR rates, long-term survival gains are controversial owing to distinctive biologic behavior mediated by the presence of hormonal receptors (HRs) that may interact with HER2 receptors. We, therefore, investigated the differences in relative survival gain provided by neoadjuvant trastuzumab-based chemotherapy on HR positive (HR+) status of patients. Methods We retrospectively analyzed women with stage II or III HER2+ breast cancer who underwent NAC followed by a breast cancer surgery between 2008 and 2013. The survival benefits of adding trastuzumab to NAC were analyzed by classifying patients into HR+ and HR negative (HR-) groups. Results Of 666 patients included in the study, 374 (52.1%) were HR+ and 319 (47.9%) were HR-. In the HR+ group, trastuzumab treatment led to higher pCR rates and significantly better breast cancer specific survival (BCSS) and overall survival (OS) than no trastuzumab treatment. However, among patients with HR- breast cancer, trastuzumab treatment showed no statistically significant difference between BCSS and OS following multivariate analysis. Conclusion We found that the addition of trastuzumab to NAC improved relative survival benefit in HER2+/HR+ patients than in HER2+/HR- patients, even though the pCR rate increases were lower. Although pCR has been regarded as a surrogate marker for estimating long-term survival benefits after NAC, it alone may not translate into real long-term oncologic outcomes in particular cancer subtypes after trastuzumab-based NAC. Further longer-term evaluation of the objective survival benefit after NAC driven by a dual HER2 block according to HR status is warranted.

Background/Aim: Multigene profiling assays provide strong evidence for predicting the prognosis of breast cancer. In this study, we aimed to evaluate the clinical validation of the BCT score with various prognostic factors. Materials and Methods: A total of 133 cases of hormone receptor-positive, cT1N0 breast cancers were analyzed. Risk stratification using the BCT score (Low, n=105; High, n=28) was analyzed with Ki67 index, p53 mutation, Immunohistochemistry 4 (IHC4) score, Nottingham Prognostic Index (NPI) and online PREDICT. Results: Ki67 index and NPI showed strong correlations with risk stratification based on BCT scores. Although the IHC4 score and online PREDICT were not associated with BCT score, there was a significant tendency of association with the online PREDICT results as the time of overall survival was increasing. Conclusion: Risk classification based on BCT scores might have aclinical significance as a prognostic marker in hormone receptor-positive, HER2-negative, early breast cancer.

To investigate the effect of neoadjuvant chemotherapy (NAC) on breast tissue composition with mammographic automated volumetric measurement. This retrospective study included 168 breast cancer patients who were treated with NAC and underwent serial mammography (pre-treatment, mid-treatment, and post-treatment) between January 2015 and October 2018. Automated volumetric measurements of the contralateral breast volume (BV), fibroglandular volume (FGV), and breast density (BD) were performed using Volpara software. BD grades were divided into 4 groups by Volpara density grade (VDG). The longitudinal changes in BV, FGV, BD, and their associated factors were evaluated. Repeated-measures analysis of variance demonstrated a significant reduction in BV, FGV, and BD over time (p

In the present study, a polyphenolic mixture was isolated from Seomae mugwort (SM; a native Korean variety of Artemisia argyi H.) via extraction with aqueous 70% methanol followed by the elution of ethyl acetate over a silica gel column. Each polyphenolic compound was analyzed using high-performance liquid chromatography coupled with tandem mass spectrometry, and compared with the literature. In addition to the 14 characterized components, one hydroxy-cinnamate, six flavonoids, and one lignan were reported for the first time, to the best our knowledge, in Artemisia argyi H. The anti-inflammatory properties of SM polyphenols were studied in lipopolysaccharide-treated RAW 264.7 macrophage cells. The SM polyphenols attenuated the activation of macrophages via the inhibition of nitric oxide production, nuclear factor-κB activation, the mRNA expression of inducible nitric oxide synthase, tumor necrosis factor α and interleukin-1β, and the phosphorylation of mitogen-activated protein kinase. Our results suggested that SM polyphenols may have therapeutic potential for the treatment of inflammatory-related diseases.

Background We report on our experience of ultrasound (US)-guided dual-localization for axillary nodes before and after neoadjuvant chemotherapy (NAC) with clip and activated charcoal to guide axillary surgery in breast cancer patients. Methods Between November 2017 and May 2018, a dual-localization procedure was performed under US guidance for the most suspicious axillary nodes noted at initial staging (before NAC, with clip) and restaging (after NAC, with activated charcoal) in 28 cytologically proven node-positive breast cancer patients. Patients underwent axillary sampling or dissection, which involved removing not only the sentinel nodes (SNs), but also clipped nodes (CNs) and tattooed nodes (TNs). Success (or failure) rates of biopsies of SNs, CNs, and TNs and inter-nodal concordance rates were determined. Sensitivities for the individual and combined biopsies were calculated. Results SN biopsy failed in four patients (14%), whereas the CN biopsy failed in one patient (4%). All TNs were identified in the surgical field. Concordance rates were 79% for CNs–TNs, 63% for CNs–SNs, and 58% for TNs–SNs. Sensitivity for SN, CN, and TN biopsy was 73%, 67%, and 67%, respectively. Sensitivity was 80% for any combination of biopsies (SN plus CN, SN plus TN, SN plus CN plus TN). Conclusions US-guided dual-localization of axillary nodes before and after NAC with clip and activated charcoal was a feasible approach that might facilitate more reliable nodal staging with less-invasive strategies in node-positive breast cancer patients.