Recurrent L3 Chordoma Presented as Intradural Extramedullary Mass With Distant Metastasis: A Case Report

Here, we report a rare case of L3 chordoma progressed to an intradural extramedullary (IDEM) mass and distant metastasis to the fascia lata. A 64-year old female patient presented to a local university hospital due to back pain and received excisional biopsy for a L3 destructive bony lesion. Local radiation therapy was initially administered, assuming a malignancy of unknown origin, but she developed cerebrospinal fluid leakage during adjuvant radiation therapy, which was managed by wound revision and lumbar drainage. As the destructive lesion progressed, she visited our hospital for a second opinion 3 months after the biopsy. After review of outside pathology, we diagnosed the lesion to be a chordoma, and performed a L3 corpectomy with cage and plate fixation. One and a half years later, positron emission tomography and computed tomography (PET-CT) revealed a right tensor fascia lata hypermetabolic lesion. Excisional biopsy confirmed a distant metastasis of the chordoma. One year later, she complained of L2 radiating pain. PET-CT and CT myelogram revealed an IDEM lesion. Surgical excision confirmed the transdural invasion of the chordoma. To our knowledge, this is the first report of an iatrogenic IDEM invasion and distant metastasis to the tensor of the fascia lata by a L3 chordoma.

Hyperammonemic Encephalopathy Mimicking Ornithine Transcarbamylase Deficiency in Fibrolamellar Hepatocellular Carcinoma: Successful Treatment with Continuous Venovenous Hemofiltration and Ammonia Scavengers / Journal of the Korean Cancer Association, 대한암학회지

Fibrolamellar hepatocellular carcinoma (FLHCC) is a rare liver cancer affecting adolescents and young adults without any pre existing liver disease. Hyperammonemic encephalopathy (HAE) is a serious paraneoplastic syndrome, and several cases of HAE have been reported in patients with FLHCC. This condition is rare; hence, there are currently no management guidelines for cancer-related HAE. Herein, we report a case of an 18-year-old man with advanced FLHCC who developed HAE during the first course of chemotherapy consisting of cisplatin, doxorubicin, 5-fluorouracil, and interferon-α. He was successfully treated with continuous venovenous hemofiltration, sodium benzoate, sodium phenylbutyrate, and amino acid supplementation for HAE. After the second course of chemotherapy, he underwent surgery, and thereafter, his ammonia levels were normal without any ammonia scavenger therapy. Treatments for HAE described here will be helpful for this rare, but serious metabolic complication of FLHCC and could partially applied to HAE related to any malignancies.

Formulation of the Scope and Key Questions of the Guideline Recommendations for Immunosuppressive Treatment in Kidney Transplantation

BACKGROUND: Although a growing number of guidelines and clinical researches are available for immunosuppressive treatment of post-transplantation, there is no clinical practice guideline for the care of kidney transplant recipients in Korea. Selection of a researchable question is the most important step in conducting qualified guideline development. Thus, we aimed to formulate key questions for Korean guideline to aid clinical decision-making for immunosuppressive treatment. METHODS: Based on previous published guidelines review, a first survey was constructed with 29 questions in the range of immunosuppressive treatments. The experts were asked to rate the clinical importance of the question using a 5-point Likert scale. The questions reached 60% or more from the first survey and additional new questions were included in the second survey. In analyzing the responses to items rated on the 9-point scale, consensus agreement on each question was defined as 75% or more of experts rating 7 to 9. RESULTS: In the first survey, 50 experts were included. Among the 29 questions, 27 were derived to get 60% or more importance and 3 new questions were additionally identified. Through the second survey, 9 questions were selected that experts reached consensus on 75% and over of the options. Finally, we developed key questions using PICO (patient, intervention, comparison, and outcome) methodology. CONCLUSION: The experts reached a high level of consensus on many of key questions in the survey. Final key questions provide direction for developing clinical practice guideline in the immunosuppressive treatment of transplantation.

Development of Agenda for Pharmaceutical Care Service Research and Development using the Analytical Hierarchy Process

BACKGROUND: Although the importance of pharmaceutical care service has been growing to meet the needs of customers with the improvement of clinical and humanistic outcomes, there was not a systematic strategy to promote research in Korea. The aim of this study was to suggest the core agendas for pharmaceutical care services research and development (R&D) considering priorities. METHODS: Based on desk researches, we developed R&D agendas for the needs of improving pharmaceutical care services in the area of institution, community, and public health. To determine the priority of agendas in developing pharmaceutical care service, analytic hierarchy process (AHP) analysis was performed by the 14 experts. Criteria and subcriteria were assessed for significance by pairwise comparisons. Then, agendas were evaluated for importance according to each subcriteria, and rank ordered considering the weight calculated by multiplying the importance scores of the criteria and the subcriteria. RESULTS: We derived 25 agendas including 13 for institutional pharmaceutical care service, 8 for community pharmaceutical care service, and 4 for public-health related pharmaceutical care service. AHP model was constructed based on 4 criteria and 8 subcriteria by a hierarchical structure. From the AHP survey, the ‘Development of pharmaceutical care service for metabolic and chronic disease’ agenda accounted for the highest priority. CONCLUSION: We have developed the R&D agendas of the pharmaceutical care service which should be promoted. The results should be utilized by the government to nationally support the development of the standards and relevant regulations related to pharmaceutical care services in Korea.

PLAG1, SOX10, and Myb Expression in Benign and Malignant Salivary Gland Neoplasms

BACKGROUND: Recent findings in molecular pathology suggest that genetic translocation and/or overexpression of oncoproteins is important in salivary gland tumorigenesis and diagnosis. We investigated PLAG1, SOX10, and Myb protein expression in various salivary gland neoplasm tissues. METHODS: A total of 113 cases of surgically resected salivary gland neoplasms at the National Cancer Center from January 2007 to March 2017 were identified. Immunohistochemical staining of PLAG1, SOX10, and Myb in tissue samples was performed using tissue microarrays. RESULTS: Among the 113 cases, 82 (72.6%) were benign and 31 (27.4%) were malignant. PLAG1 showed nuclear staining and normal parotid gland was not stained. Among 48 cases of pleomorphic adenoma, 29 (60.4%) were positive for PLAG1. All other benign and malignant salivary gland neoplasms were PLAG1-negative. SOX10 showed nuclear staining. In normal salivary gland tissues SOX10 was expressed in cells of acinus and intercalated ducts. In benign tumors, SOX10 expression was observed in all pleomorphic adenoma (48/48), and basal cell adenoma (3/3), but not in other benign tumors. SOX10 positivity was observed in nine of 31 (29.0%) malignant tumors. Myb showed nuclear staining but was not detected in normal parotid glands. Four of 31 (12.9%) malignant tumors showed Myb positivity: three adenoid cystic carcinomas (AdCC) and one myoepithelial carcinoma with focal AdCC-like histology. CONCLUSIONS: PLAG1 expression is specific to pleomorphic adenoma. SOX10 expression is helpful to rule out excretory duct origin tumor, but its diagnostic value is relatively low. Myb is useful for diagnosing AdCC when histology is unclear in the surgical specimen.

Selection of Tasks for Assessment of Pharmacy Clinical Performance in Korean Pharmacist Licensure Examination: Results of an Expert Survey

OBJECTIVE: As the demands of pharmacist's role and quality performance have increased, the verification of pharmacist's ability has been required. In this study, we aimed to select appropriate items for assessment of pharmacist's knowledge, attitude and performance. METHODS: Based on the pharmacist job analysis, we selected duties and tasks in consideration of applying pharmacy practical examination through brainstorming of internal researchers and group discussion with experts. Survey was conducted to evaluate the tasks according to the criteria detailed below: Realistic, Understandable, Measurable, Behavioral and Achievable (RUMBA). The subjects included professors at colleges of pharmacy and instructors of institutional or community pharmacy settings. RESULTS: Nine duties including 41 tasks were drawn for the survey through primary internal researchers. Of the 90 respondents, 95.6% were professors or preceptors who was engaged in practical training, and 62.2% had more than five years of practical experience. As a result of survey and discussion with expert panel, selected seven duties were selected as followings: ‘Patient (customer) reception’, ‘Drug preparation and distribution’, ‘Patient care’, ‘Administration’, ‘Patient counseling’, ‘Non-prescription medication counseling’, and ‘Provision of drug information’. The final 20 tasks from seven duties were chosen to assess skills that a pharmacist should be able to perform. CONCLUSION: This is the first study to select the items that can be included in pharmacist practical examination in the future, based on the RUMBA criteria. As a next step, it is necessary to study how to implement these items.

Regulation of Pharmacogene Expression by microRNA in The Cancer Genome Atlas (TCGA) Research Network

Individual differences in drug responses are associated with genetic and epigenetic variability of pharmacogene expression. We aimed to identify the relevant miRNAs which regulate pharmacogenes associated with drug responses. The miRNA and mRNA expression profiles derived from data for normal and solid tumor tissues in The Cancer Genome Atlas (TCGA) Research Network. Predicted miRNAs targeted to pharmacogenes were identified using publicly available databases. A total of 95 pharmacogenes were selected from cholangiocarcinoma and colon adenocarcinoma, as well as kidney renal clear cell, liver hepatocellular, and lung squamous cell carcinomas. Through the integration analyses of miRNA and mRNA, 35 miRNAs were found to negatively correlate with mRNA expression levels of 16 pharmacogenes in normal bile duct, liver, colon, and lung tissues (p<0.05). Additionally, 36 miRNAs were related to differential expression of 32 pharmacogene mRNAs in those normal and tumorigenic tissues (p<0.05). These results indicate that changes in expression levels of miRNAs targeted to pharmacogenes in normal and tumor tissues may play a role in determining individual variations in drug response.

Attitudes to proposed assessment of pharmacy skills in Korean pharmacist licensure examination / 보건의료교육평가

PURPOSE: The survey aimed to obtain opinions about a proposed implementation of pharmacy skills assessment in Korean pharmacist licensure examination (KPLE). METHODS: A 16-question survey was distributed electronically to 2,738 people including 570 pharmacy professors of 35 pharmacy schools, 550 preceptors from 865 practice sites and 1,618 students who graduated in 2015. The survey solicited responses concerning the adequacy of the current KPLE in assessing pharmacy knowledge/skills/attitudes, deficiencies of pharmacy skills testing in assessing the professional competencies necessary for pharmacists, plans for pharmacy skills tests in the current KPLE, and subject areas of pharmacy practice. RESULTS: A total of 466 surveys were returned. The current exam is not adequate for assessing skills and attitudes according to 42%–48% of respondents. Sixty percent felt that skills test is necessary to assess qualifications and professional competencies. Almost two-thirds of participants stated that testing should be implemented within 5 years. More than 60% agreed that candidates should be graduates and that written and skills test scores can be combined for pass-fail decisions. About 70% of respondents felt that the test should be less than 2 hours in duration. Over half of the respondents thought that the assessor should be a pharmacy faculty member with at least 5 years of clinical experience. Up to 70% stated that activities related to patient care were appropriate and practical for the scope of skills test. CONCLUSION: Pharmacy skills assessment was supported by the majority of respondents.

Meningeal Solitary Fibrous Tumors with Delayed Extracranial Metastasis

BACKGROUND: The term solitary fibrous tumor (SFT) is preferred over meningeal hemangiopericytoma (HPC), because NAB2-STAT6 gene fusion has been observed in both intracranial and extracranial HPCs. HPCs are now considered cellular variants of SFTs. METHODS: This study analyzes 19 patients with STAT6-confirmed SFTs, who were followed for over 11 years in a single institution. Ten patients (10/19, 56.2%) had extracranial metastases (metastatic group), while the remainder (9/19) did not (non-metastatic group). These two groups were compared clinicopathologically. RESULTS: In the metastatic group, the primary metastatic sites were the lungs (n = 6), bone (n = 4), and liver (n = 3). There was a mean lag time of 14.2 years between the diagnosis of the initial meningeal tumor to that of systemic metastasis. The median age at initial tumor onset was 37.1 years in the metastatic group and 52.5 in the non-metastatic group. The 10-year survival rates of the metastatic- and non-metastatic groups were 100% and 33%, respectively. The significant prognostic factors for poor outcomes on univariate analysis included advanced age (≥45 years) and large initial tumor size (≥5 cm). In contrast, the patients with higher tumor grade, high mitotic rate (≥5/10 high-power fields), high Ki-67 index (≥5%), and the presence of necrosis or CD34 positivity showed tendency of poor prognosis but these parameters were not statistically significant poor prognostic markers. CONCLUSIONS: Among patients with SFTs, younger patients (<45 years) experienced longer survival times and paradoxically had more frequent extracranial metastases after long latent periods than did older patients. Therefore, young patients with SFTs require careful surveillance and follow-up for early detection of systemic metastases.

Clinical Outcomes of Multidisciplinary Team Care on the Regulation of Chronic Kidney Disease - Mineral and Bone Disorder (CKD-MBD) in Patients Undergoing Dialysis

BACKGROUND: Multidisciplinary team care (MTC) is a collaborative approach to treatment plan and ongoing care. We aimed to evaluate the clinical effect of MTC on the regulation of chronic kidney disease-mineral and bone disorder (CKD-MBD) complications in dialysis patients. METHODS: This retrospective observational study was approved by the institutional review board. Among patients who have undergone dialysis at admission, the patients admitted to the nephrology ward were allocated to MTC group, and the others to usual care (UC) group. The MTC group had collaborative care by nephrologists, nurses, pharmacists, and nutritionists. The endpoints were the regulation of corrected calcium (cCa) and phosphate (P), the percent of patients in target level of cCa-P product (cCa×P), and the prescription rate of non-calcium based P-binders. RESULTS: A total of 163 patients were included from January to December 2009. A significant difference was shown in the percentage of patients in target cCa×P level at admission (MTC vs. UC, 81.40% vs. 91.67%; P = 0.038), but there was no significant difference at discharge. During admission, the cCa and P levels of patients in only UC group were significantly changed. In addition, compared with UC group, patients in MTC group were more likely prescribed appropriate P-binders, when they had higher cCa×P levels than 55 mg²/dL² (P <0.001). CONCLUSION: It was found that MTC had beneficial effect on improving the regulation of CKD-MBD and the appropriate phosphate binder uses. Therefore, application of the MTC is anticipated to enhance quality of clinical care in chronic diseases.

Qualitative Study for Medication Use among Visually Impaired in Korea

OBJECTIVE: The visually impaired have limited access to health care services and related information, and thus, they can have serious hurdles against properly taking medications. Despite that it is important to improve self-care ability of the visually impaired for correct medication use, there have been few studies investigating their needs for health care services in Korea, particularly focusing on proper medication usage. This study is to explore safety-related issues regarding mediation usage among the visually impaired based on in-depth interview. We particularly focus on any obstacles for safe use of medicines including experience on medication-related adverse effects in order to provide preliminary evidence for policy measures to improve proper medication use among the visually impaired. METHODS: Study sample was visually impaired individuals who resided in Seoul area and were registered in the National Association of Visually Impaired. The association helped the process of recruiting the study participants. In-depth interview for each study participants was conducted. Each interview was recorded and later converted into a written script to extract core contents for the analysis. RESULTS: The study participants comprised of three women (42.9%) and four men (57.1%). One was in his 20's, and there were four participants in 30's and two in 40's. Fully impaired participants were majority (5 out of 7). Limitation to physical access to health care providers and health information were the key factors to hamper safe medication utilization among the study participants. Difficulty reading medication information and may take the wrong medication or incorrect doses of medication, resulting in serious consequences, including overdose or inadequate treatment of health problems. Visually impaired patients report increased anxiety related to medication management and must rely on others to obtain necessary drug information. Pharmacists have a unique opportunity to pursue accurate medication adherence in this special population. This article reviews literature illustrating how severe medication mismanagement can occur in the visually impaired elderly and presents resources and solutions for pharmacists to take a larger role in adherence management in this population. CONCLUSION: The visually impaired had difficulties reading medication information and identifying medicines, and took incorrect doses of medications. Public support for safe medication use and medication management among the visually impaired is necessary.

Pharmaceutical Care Services of Community Pharmacies in Korea Through the Review of Literature

BACKGROUND: The recent change in pharmaceutical education system following the paradigm shift to patient-oriented pharmacy service requires an in-depth discussion to reorganize a future direction and establish a basis for maximizing social values of community pharmacy service. OBJECTIVE: This study was conducted to review the current status of community pharmacy service provision in Korea based on published literatures. METHODS: The electronic databases of National Digital Science Library and Electronic National Assembly Library were used to search the journal articles and dissertation papers. A search term "community pharmacy" was used and the published period was limited to papers published after year 2001, when the legal separation of prescribing and dispensing was implemented. Relevant study reports were also searched manually. Information about pharmacy service provision and study outcomes were retrieved from the selected papers, and classified by predefined individual service scope. RESULTS: A total 33 papers reporting services provided by community pharmacies were selected (journal article 11, dissertation paper 17, and study report 5). Pharmacy services identified in these papers could be classified into prescription dispensing service, pharmaceutical care service, self medication service, other products service, and health promotion service. Twenty papers reported prescription dispensing services, three papers reported pharmaceutical care service, and only two papers reported health promotion service. Current community pharmacy services are highly dependent on prescription drugs while expanded services such as pharmaceutical care and health promotion are peripheral. Most prevalent research topic was medication counseling service (18 papers), reflecting that community pharmacists generally consider it to be the most important and fundamental service. Overall, current pharmacy services are very limited and focus on prescription dispensing service. CONCLUSION: At this point of time requiring expansion and quality improvement of community pharmacy services, we suggest further lively discussion to strengthen pharmacist's functional identity and set conditions for providing socially expected services.

Effects of Fixation and Storage of Human Tissue Samples on Nucleic Acid Preservation

BACKGROUND: Because of recent advances in the molecular diagnosis of cancer patients, tissue quality has become more important in daily practice. METHODS: To evaluate the effects of fixative, duration of fixation, decalcification, and storage periods on nucleic acid integrity, DNA and RNA were extracted from gastrointestinal cancer tissue. The yield and purity were analyzed, and polymerase chain reaction (PCR) for glyceraldehyde 3-phosphate dehydrogenase (GAPDH; 60 bp), beta-actin (148 bp), and human growth hormone (hGH; 434 bp) and real-time reverse transcription-PCR for beta-actin (97 bp) were performed. RESULTS: All formalin-fixed paraffin-embedded (FFPE) and methacarn-fixed paraffin-embedded (MFPE) samples tested positive for GAPDH and beta-actin by PCR. hGH was successfully detected in all MFPE samples, but in only 46.7% of the FFPE samples. Prolonged formalin fixation resulted in fewer GAPDH and beta-actin PCR products, and amplification of hGH was not successful. The PCR and reverse transcription-PCR results were significantly affected by the duration of decalcification. The yield, purity, and integrity of mRNA progressively decreased with increased storage periods of paraffin blocks. CONCLUSIONS: Fixation and storage should therefore be standardized in order to improve the quality of molecular pathologic diagnosis.