Clinicopathologic characterization of cervical metastasis from an unknown primary tumor: a multicenter study in Korea

Background@#Research regarding cervical metastasis from an unknown primary tumor (CUP) according to human papillomavirus (HPV) and Epstein-Barr virus (EBV) status in Korea has been sporadic and small-scale. This study aims to analyze and understand the characteristics of CUP in Korea according to viral and p16 and p53 status through a multicenter study. @*Methods@#Ninety-five cases of CUP retrieved from six hospitals in Korea between January 2006 and December 2016 were subjected to high-risk HPV detection (DNA in situ hybridization [ISH] or real-time polymerase chain reaction), EBV detection (ISH), and immunohistochemistry for p16 and p53. @*Results@#CUP was HPV-related in 37 cases (38.9%), EBV-related in five cases (5.3%), and unrelated to HPV or EBV in 46 cases (48.4%). HPV-related CUP cases had the best overall survival (OS) (p = .004). According to the multivariate analysis, virus-unrelated disease (p = .023) and longer smoking duration (p < .005) were prognostic factors for poor OS. Cystic change (p = .016) and basaloid pattern (p < .001) were more frequent in HPV-related cases, and lymphoepithelial lesion was frequent in EBV-related cases (p = .010). There was no significant association between viral status and p53 positivity (p = .341), smoking status (p = .728), or smoking duration (p = .187). Korean data differ from Western data in the absence of an association among HPV, p53 positivity, and smoking history. @*Conclusions@#Virus-unrelated CUP in Korea had the highest frequency among all CUP cases. HPV-related CUP is similar to HPV-mediated oropharyngeal cancer and EBVrelated CUP is similar to nasopharyngeal cancer in terms of characteristics, respectively.

A Case of Auricular Schwannoma After Trauma / 대한이비인후과학회지

Schwannoma is a slowly-growing, benign tumor that originates from the Schwann cell and is rarely found in the auricle. In this article, we describe a 20-year-old male patient with an approximately 2 cm auricular mass located in the antitragus of the left ear. The mass was slowlygrowing following an auricular trauma. The mass was completely removed by local excision and the histopathologic review confirmed the diagnosis as an auricular schwannoma. Characteristic immunohistochemical findings may be helpful in differential diagnosis of other tumors. Herein, we present with a literature review a rare case of auricular schwannoma following a trauma.

Utilization of Evidence-Based Clinical Nursing Practice Guidelines in Tertiary Hospitals and General Hospitals / 임상간호연구

Purpose@#The purpose of this study was to investigate the actual utilization of clinical practice guidelines developed by Hospital Nurses Association. @*Methods@#The subjects were 70 nurses who were in charge of guideline distributions in 70 advanced general hospital and general hospitals with 500 beds or more nationwide.Data were collected between June and August, 2020 by mail (return rate: 88.6%). Data were analyzed using descriptive statistics, t-test, and ANOVA with SPSS/WIN 24.0. @*Results@#Among the clinical practice guidelines developed by Hospital Nurses Association, 72.9~90.1% were placed with book and electronic file in nursing department and 24.3~35.8% were placed with book and electronic file in each nursing unit at hospital. The average number of utilized clinical practice guidelines were 3.96±3.88, and average score of guideline utilization was score 2.85±0.79 which means ‘use sometimes’. @*Conclusion@#To improve the distribution and utilization of the clinical practice guidelines, it is necessary to enhance the recognition of values of evidence based nursing practice targeting head of nursing department and to stimulate the distribution and utilization of the clinical practice guidelines using diverse education programs for staff nurses.

Development and Validation of a Korean Nursing Work Environment Scale for Critical Care Nurses / 임상간호연구

Purpose@#The purpose of this study was to develop a Korean nursing work environment scale for critical care nurses (KNWES-CCN) and verify its validity and reliability. @*Methods@#A total of 46 preliminary items were selected using content validity analysis of experts on 64 candidate items derived through literature reviews and in-depth interviews with critical care nurses. 535 critical care nurses from 21 hospitals responded to the preliminary questionnaire from February to March 2021. The collected data were analysed using construct, convergent and discriminant validities, and internal consistency and test-retest reliability. @*Results@#The 23 items in 4 factors accounted for 55.6% of the total variance were identified through item analysis and exploratory factor analysis (EFA). EFA was performed with maximum likelihood method including direct oblimin method. In the confirmatory factor analysis, KNWES-CCN consisted of 21 items in 4 factors by deleting the items that were not meet the condition that the factor loading over .50 or the squared multiple correlation over .30. This model was considered to be suitable because it satisfied the fit index and acceptable criteria of the model [x2 =440.47 (p<.001), CMIN/DF=2.41, GFI=.86, SRMR=.06, RMSEA=.07, TLI=.90, CFI=.91]. The item total correlation values ranged form .32 to .73 and its internal consistency was Cronbach's ⍺=.92. The reliability of the test-retest correlation coefficient was .72 and the intra-class correlation coefficient was .83. @*Conclusion@#The KNWES-CCN showed good validity and reliability. Therefore, it is expected that the use of this scale would measure and improve nursing work environment for critical care nurses in Korea.

Standardization of the pathologic diagnosis of appendiceal mucinous neoplasms

Although the understanding of appendiceal mucinous neoplasms (AMNs) and their relationship with disseminated peritoneal mucinous disease have advanced, the diagnosis, classification, and treatment of AMNs are still confusing for pathologists and clinicians. The Gastrointestinal Pathology Study Group of the Korean Society of Pathologists (GPSG-KSP) proposed a multicenter study and held a workshop for the “Standardization of the Pathologic Diagnosis of the Appendiceal Mucinous Neoplasm” to overcome the controversy and potential conflicts. The present article is focused on the diagnostic criteria, terminologies, tumor grading, pathologic staging, biologic behavior, treatment, and prognosis of AMNs and disseminated peritoneal mucinous disease. In addition, GPSG-KSP proposes a checklist of standard data elements of appendiceal epithelial neoplasms to standardize pathologic diagnosis. We hope the present article will provide pathologists with updated knowledge on how to handle and diagnose AMNs and disseminated peritoneal mucinous disease.

Standardization of the pathologic diagnosis of appendiceal mucinous neoplasms

Although the understanding of appendiceal mucinous neoplasms (AMNs) and their relationship with disseminated peritoneal mucinous disease have advanced, the diagnosis, classification, and treatment of AMNs are still confusing for pathologists and clinicians. The Gastrointestinal Pathology Study Group of the Korean Society of Pathologists (GPSG-KSP) proposed a multicenter study and held a workshop for the “Standardization of the Pathologic Diagnosis of the Appendiceal Mucinous Neoplasm” to overcome the controversy and potential conflicts. The present article is focused on the diagnostic criteria, terminologies, tumor grading, pathologic staging, biologic behavior, treatment, and prognosis of AMNs and disseminated peritoneal mucinous disease. In addition, GPSG-KSP proposes a checklist of standard data elements of appendiceal epithelial neoplasms to standardize pathologic diagnosis. We hope the present article will provide pathologists with updated knowledge on how to handle and diagnose AMNs and disseminated peritoneal mucinous disease.

Updates of Nursing Practice Guideline for Enteral Nutrition / 임상간호연구

Purpose@#The purpose of this study was to update the previously developed nursing practice guideline for enteral nutrition (EN). @*Methods@#The guideline update was done in 22 steps using standardized methodology for nursing practice guidelines. @*Results@#The updated EN guideline consisted of 16 domains and 228 recommendations. The domains and number of recommendations in each domain were for IDSA (Infectious Diseases Society of America): 8 on general instruction, 9 on general instruction for special nutrition, 9 on general instruction for EN, 3 on assessment of EN, 10 on access to EN, 18 on EN device insertion, 16 on selection and preparation of nutritional supplements, 46 on administration and stopping EN, 22 on maintenance and management of EN, 9 on monitoring EN, 16 on prevention and management of complications of EN, 18 on medication administration, 20 on EN in various situations, 20 on prevention of errors, 1 on nursing education, and 3 on nursing documentation. For the levels of evidence, there were 9.7% for level I, 13.1% for level II, 62.5% for level III and 1.1% for GRADE (Grading of Recommendations Assessment, Development and Evaluation): 3.3% for low, 0.8% for moderate, 9.3% for very low. A total of 133 recommendations were newly developed and 10 previous recommendations were modified. @*Conclusion@#This updated EN nursing practice guideline can be used to enhance evidence-based practice in fundamentals of nursing practice and it should be disseminated to nurses nationwide in order to improve the efficiency of EN practice.

Extraskeletal Ewing's Sarcoma of the Thoracic Nerve Root: A Case Report

Extraskeletal Ewing's sarcoma (EES) is a rare malignant soft tissue tumor which is morphologically indistinguishable from skeletal ES. EES usually occurs in young adults and children and there has been only one case reported in a patient aged over 70 years old. We report a case of an EES arising from the first thoracic spinal nerve root in a 73-year-old female, which was misdiagnosed as benign nerve sheath tumor in preoperative imaging evaluation.

The Structural Equation Model of Organizational Culture, Authentic Leadership, Self-Esteem, and Bullying in Nurses at Critical Care Units / 임상간호연구

PURPOSE@#The purpose of this study were to identify the influential factors of bullying of intensive care nurses and to suggest a final structural model based on identified relationships between nursing organizational culture, authentic leadership, self-esteem, and bullying in the workplace.@*METHODS@#Data were collected from 221 nurses at intensive care units in eight general hospitals using structured questionnaires and analyzed by structural equation modeling.@*RESULTS@#In this study, the average of bullying in the workplace was 1.34±0.40, nursing organizational culture was 3.31±0.47, self-esteem was 2.79±0.44, and authentic leadership was 3.61±0.60. The factors affecting nursing organizational culture were authentic leadership (β=.54, p<.001) and self-esteem (β=.24, p=.002) that had direct positive effects on the nursing organizational culture. The nursing organizational culture had also a direct effect on reducing workplace bullying (β=−.45, p<.001). Authentic leadership (β=−.24, p=.004) and self-esteem (β=−.11, p=.004) had indirect effects on workplace bullying, which was mediated by the nursing organizational culture.@*CONCLUSION@#To understand and reduce workplace bullying, evaluating a nursing organizational culture should be preceded. Based on the finding of this study, an intervention for increasing authentic leadership and self-esteem of nurses can positively help to create the nursing organizational culture and then reduce workplace bullying.

A Case of Lateral Ectopic Thyroid Mimicking the Metastatic Lymphadenopathy / 대한이비인후과학회지

Ectopic thyroid means that thyroid tissue is present at an unusual area rather than at the orthotropic thyroid position. The most common form of ectopic thyroid is lingual thyroid, followed by thyroglossal duct cyst. Ectopic thyroid in the lateral neck area is extremely rare, with only a few case reports found in the literature review. Several studies recommended that metastasizing malignancy should be considered in lateral ectopic thyroid. Described here is a case of 60 year-old woman with lateral ectopic thyroid, which was newly found during a follow-up and was mistaken for metastatic lymphadenopathy.

A Case of Lateral Ectopic Thyroid Mimicking the Metastatic Lymphadenopathy / 대한이비인후과학회지

Ectopic thyroid means that thyroid tissue is present at an unusual area rather than at the orthotropic thyroid position. The most common form of ectopic thyroid is lingual thyroid, followed by thyroglossal duct cyst. Ectopic thyroid in the lateral neck area is extremely rare, with only a few case reports found in the literature review. Several studies recommended that metastasizing malignancy should be considered in lateral ectopic thyroid. Described here is a case of 60 year-old woman with lateral ectopic thyroid, which was newly found during a follow-up and was mistaken for metastatic lymphadenopathy.

In Vivo Validation Model of a Novel Anti-Inflammatory Scaffold in Interleukin-10 Knockout Mouse

BACKGROUND: We fabricated anti-inflammatory scaffold using Mg(OH)2-incorporated polylactic acid-polyglycolic acid copolymer (MH-PLGA). To demonstrate the anti-inflammatory effects of the MH-PLGA scaffold, an animal model should be sensitive to inflammatory responses. The interleukin-10 knockout (IL-10 KO) mouse is a widely used bowel disease model for evaluating inflammatory responses, however, few studies have evaluated this mouse for the anti-inflammatory scaffold. METHODS: To compare the sensitivity of the inflammatory reaction, the PLGA scaffold was implanted into IL-10 KO and C57BL/6 mouse kidneys. Morphology, histology, immunohistochemistry, and gene expression analyses were carried out at weeks 1, 4, 8, and 12. The anti-inflammatory effect and renal regeneration potency of the MH-PLGA scaffold was also compared to those of PLGA in IL-10 KO mice. RESULTS: The PLGA scaffold-implanted IL-10 KO mice showed kidneys relatively shrunken by fibrosis, significantly increased inflammatory cell infiltration, high levels of acidic debris residue, more frequent CD8-, C-reactive protein-, and ectodysplasin A-positive cells, and higher expression of pro-inflammatory and fibrotic factors compared to the control group. The MH-PLGA scaffold group showed lower expression of pro-inflammatory and fibrotic factors, low immune cell infiltration, and significantly higher expression of anti-inflammatory factors and renal differentiation related genes compared to the PLGA scaffold group. CONCLUSION: These results indicate that the MH-PLGA scaffold had anti-inflammatory effects and high renal regeneration potency. Therefore, IL-10 KO mice are a suitable animal model for in vivo validation of novel anti-inflammatory scaffolds.

Laminin and Platelet-Derived Growth Factor-BB Promote Neuronal Differentiation of Human Urine-Derived Stem Cells

Urine-derived stem cells (USCs) are considered as a promising cell source capable of neuronal differentiation. In addition, specific growth factors and extracellular matrix are essential for enhancing their neuronal differentiation efficiency. In this study, we investigated the possibility of neuronal differentiation of USCs and the role of laminin and platelet-derived growth factor BB (PDGF-BB) as promoting factors. USCs were isolated from fresh urine of healthy donors. Cultured USCs were adherent to the plate and their morphology was similar to the cobblestone. In addition, they showed chromosome stability, rapid proliferation rate, colony forming capacity, and mesenchymal stem cell characteristics. For inducing the neuronal differentiation, USCs were cultured for 14 days in neuronal differentiation media supplemented with/without laminin and/or PDGF-BB. To identify the expression of neuronal markers, RT-PCR, flow cytometry analysis and immunocytochemistry were used. After neuronal induction, the cells showed neuron-like morphological change and high expression level of neuronal markers. In addition, laminin and PDGF-BB respectively promoted the neuronal differentiation of USCs and the combination of laminin and PDGF-BB showed a synergistic effect for the neuronal differentiation of USCs. In conclusion, USCs are noteworthy cell source in the field of neuronal regeneration and laminin and PDGF-BB promote their neuronal differentiation efficiency.

Critical Care Nursing Courses in Bachelor of Science in Nursing Programs: Present and Future Directions / 중환자간호학회지

PURPOSE: This study examined the status of critical care nursing education in bachelor of science in nursing (BSN) to suggest future directions.METHODS: The target of the survey was 185 BSN programs that were certified by the Korean Accreditation Board of Nursing Education as of October 31, 2016. We structurally reviewed the curriculums and the course syllabi.RESULTS: Forty-eight courses of 42 BSN programs were analyzed. Only five programs offered both theoretical and practical courses in critical care nursing; 22 offered theoretical courses and 26 offered practical courses. Most courses were offered as electives with 1 or 2 credits, and were taught by faculty who were experts in adult health nursing.CONCLUSION: The results show that there is a quantitative shortage of critical care nursing education in the curriculum of BSN programs in Korea. The lack of knowledge and skills on critical care can lead to a burden of new intensive care unit nurses and is a threat to patients' health. It is necessary to develop a practical and integrative curriculum for critical care nursing education.

Molecular Testing for Gastrointestinal Cancer

With recent advances in molecular diagnostic methods and targeted cancer therapies, several molecular tests have been recommended for gastric cancer (GC) and colorectal cancer (CRC). Microsatellite instability analysis of gastrointestinal cancers is performed to screen for Lynch syndrome, predict favorable prognosis, and screen patients for immunotherapy. The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor has been approved in metastatic CRCs with wildtype RAS (KRAS and NRAS exon 2–4). A BRAF mutation is required for predicting poor prognosis. Additionally, amplification of human epidermal growth factor receptor 2 (HER2) and MET is also associated with resistance to EGFR inhibitor in metastatic CRC patients. The BRAF V600E mutation is found in sporadic microsatellite unstable CRCs, and thus is helpful for ruling out Lynch syndrome. In addition, the KRAS mutation is a prognostic biomarker and the PIK3CA mutation is a molecular biomarker predicting response to phosphoinositide 3-kinase/AKT/mammalian target of rapamycin inhibitors and response to aspirin therapy in CRC patients. Additionally, HER2 testing should be performed in all recurrent or metastatic GCs. If the results of HER2 immunohistochemistry are equivocal, HER2 silver or fluorescence in situ hybridization testing are essential for confirmative determination of HER2 status. Epstein-Barr virus–positive GCs have distinct characteristics, including heavy lymphoid stroma, hypermethylation phenotype, and high expression of immune modulators. Recent advances in next-generation sequencing technologies enable us to examine various genetic alterations using a single test. Pathologists play a crucial role in ensuring reliable molecular testing and they should also take an integral role between molecular laboratories and clinicians.

Prognostic Significance of a Micropapillary Pattern in Pure Mucinous Carcinoma of the Breast: Comparative Analysis with Micropapillary Carcinoma

BACKGROUND: Mucinous carcinoma of the breast is an indolent tumors with a favorable prognosis; however, micropapillary features tend to lead to aggressive behavior. Thus, mucinous carcinoma and micropapillary carcinoma exhibit contrasting biologic behaviors. Here, we review invasive mucinous carcinoma with a focus on micropapillary features and correlations with clinicopathological factors. METHODS: A total of 64 patients with invasive breast cancer with mucinous or micropapillary features were enrolled in the study. Of 36 pure mucinous carcinomas, 17 (47.2%) had micropapillary features and were termed mucinous carcinoma with micropapillary features (MUMPC), and 19 (52.8%) had no micropapillary features and were termed mucinous carcinoma without micropapillary features. MUMPC were compared with 15 invasive micropapillary carcinomas (IMPC) and 13 invasive ductal and micropapillary carcinomas (IDMPC). RESULTS: The clinicopathological factors of pure mucinous carcinoma and MUMPC were not significantly different. In contrast to IMPC and IDMPC, MUMPC had a low nuclear grade, lower mitotic rate, higher expression of hormone receptors, negative human epidermal growth factor receptor 2 (HER2) status, lower Ki-67 proliferating index, and less frequent lymph node metastasis (p < .05). According to univariate analyses, progesterone receptor, HER2, T-stage, and lymph node metastasis were significant risk factors for overall survival; however, only T-stage remained significant in a multivariate analysis (p < .05). CONCLUSIONS: In contrast to IMPC and IDMPC, the micropapillary pattern in mucinous carcinoma does not contribute to aggressive behavior. However, further analysis of a larger series of patients is required to clarify the prognostic significance of micropapillary patterns in mucinous carcinoma of the breast.

Diversity of vir Genes in Plasmodium vivax from Endemic Regions in the Republic of Korea: an Initial Evaluation

Variant surface antigens (VSAs) encoded by pir families are considered to be the key proteins used by many Plasmodium spp. to escape the host immune system by antigenic variation. This attribute of VSAs is a critical issue in the development of a novel vaccine. In this regard, a population genetic study of vir genes from Plasmodium vivax was performed in the Republic of Korea (ROK). Eighty-five venous blood samples and 4 of the vir genes, namely vir 27, vir 21, vir 12, and vir 4, were selected for study. The number of segregating sites (S), number of haplotypes (H), haplotype diversity (Hd), DNA diversity (π and Θw), and Tajima’s D test value were conducted. Phylogenetic trees of each gene were constructed. The vir 21 (S=143, H=22, Hd=0.827) was the most genetically diverse gene, and the vir 4 (S=6, H=4, Hd=0.556) was the opposite one. Tajima’s D values for vir 27 (1.08530, P>0.1), vir 12 (2.89007, P0.1) were positive, and that of vir 4 (−1.32162, P>0.1) was negative. All phylogenetic trees showed 2 clades with no particular branching according to the geographical differences and cluster. This study is the first survey on the vir genes in ROK, providing information on the genetic level. The sample sequences from vir 4 showed a clear difference to the Sal-1 reference gene sequence, whereas they were very similar to those from Indian isolates.

Predictors of Recurrent Ductal Carcinoma In Situ after Breast-Conserving Surgery / 한국유방암학회지

PURPOSE: Local recurrence is a major concern in patients who have undergone surgery for ductal carcinoma in situ (DCIS). The present study assessed whether the expression levels of hormone receptors, human epidermal growth factor receptor 2 (HER2), and Ki-67, as well as resection margin status, tumor grade, age at diagnosis, and adjuvant hormonal therapy and radiotherapy (RT) are associated with recurrence in women with DCIS. METHODS: In total, 111 patients with DCIS were included in the present study. The invasive and noninvasive recurrence events were recorded. The clinicopathological features; resection margins; administration of hormonal therapy and RT; expression statuses of estrogen receptor (ER), progesterone receptor (PR), and HER2; Ki-67 expression; and molecular subtypes were evaluated. Logistic regression analysis was performed to examine the risk factors for recurrence. RESULTS: Recurrence was noted in 27 of 111 cases (24.3%). Involvement of resection margins, low tumor grade, high Ki-67 expression, and RT were independently associated with an increase in the recurrence rate (p<0.05, Pearson chi-square test). The recurrence rate was not significantly associated with patient age; ER, PR, and HER2 statuses; molecular subtype; and hormonal therapy. CONCLUSION: The results of the present study suggested that the involvement of resection margins, low tumor grade, high Ki-67 index, and the absence of adjuvant RT were independently associated with increased recurrence in patients with DCIS. Future studies should be conducted in a larger cohort of patients to further improve the identification of patients at high-risk for DCIS recurrence.

Effective High-Throughput Blood Pooling Strategy before DNA Extraction for Detection of Malaria in Low-Transmission Settings

In the era of (pre) elimination setting, the prevalence of malaria has been decreasing in most of the previously endemic areas. Therefore, effective cost- and time-saving validated pooling strategy is needed for detection of malaria in low transmission settings. In this study, optimal pooling numbers and lowest detection limit were assessed using known density samples prepared systematically, followed by genomic DNA extraction and nested PCR. Pooling strategy that composed of 10 samples in 1 pool, 20 µl in 1 sample, was optimal, and the parasite density as low as 2 p/µl for both falciparum and vivax infection was enough for detection of malaria. This pooling method showed effectiveness for handling of a huge number of samples in low transmission settings (<9% positive rate). The results indicated that pooling of the blood samples before DNA extraction followed by usual nested PCR is useful and effective for detection of malaria in screening of hidden cases in low-transmission settings.

Prevalence of Clonorchis sinensis Infection among Residents along 5 Major Rivers in the Republic of Korea

Clonorchis sinensis is currently the most important parasite affecting public health problems in the Republic of Korea. We investigated the prevalence of C. sinensis infection among residents living along 5 major rivers in Korea. A total of 42,562 individual stool samples were collected from 37 localities and examined using the formalin-ether sedimentation technique. Helminth eggs were detected in 4,052 (9.5%) residents and 3,586 (8.4%) were infected with C. sinensis. The egg positive rate of C. sinensis in Nakdong, Seomjin, Geum, Yeongsan, and Han River was 11.7%, 9.9%, 6.5%, 3.1%, and 1.0%, respectively. The overall prevalence of clonorchiasis by sex was 11.2% in males and 6.2% in females. The age-prevalence was the highest in the 50-59 years band. It has been reconfirmed that the endemicity of clonorchiasis is higher in southern areas of Korea, especially along Nakdong and Seomjin Rivers. A combination of continuous control programs with health education initiatives is urgently required in these highly endemic areas of clonorchiasis in Korea.