Background: Nilotinib is a tyrosine kinase inhibitor approved by the Ministry of Food and Drug Safety for frontline and 2nd line treatment of Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML). This study aimed to confirm the safety and efficacy of nilotinib in routine clinical practice within South Korea. Methods: An open-label, multicenter, single-arm, 12-week observational post-marketing surveillance (PMS) study was conducted on 669 Korean adult patients with Ph + CML from December 24, 2010, to December 23, 2016. The patients received nilotinib treatment in routine clinical practice settings. Safety was evaluated by all types of adverse events (AEs) during the study period, and efficacy was evaluated by the complete hematological response (CHR) and cytogenetic response. Results: During the study period, AEs occurred in 61.3% (410 patients, 973 events), adverse drug reactions (ADRs) in 40.5% (271/669 patients, 559 events), serious AEs in 4.5% (30 patients, 37 events), and serious ADRs in 0.7% (5 patients, 8 events). Furthermore, unexpected AEs occurred at a rate of 6.9% (46 patients, 55 events) and unexpected ADRs at 1.2% (8 patients, 8 events). As for the efficacy results, CHR was achieved in 89.5% (442/494 patients), and minor cytogenetic response or major cytogenetic response was achieved in 85.8% (139/162 patients). Conclusion This PMS study shows consistent results in terms of safety and efficacy compared with previous studies. Nilotinib was well tolerated and efficacious in adult Korean patients with Ph + CML in routine clinical practice settings.

Determining blood loss [100% – RBV (%)] is challenging in the management of haemorrhagic shock. We derived an equation estimating RBV (%) via serial haematocrits (Hct1 , Hct2 ) by fixing infused crystalloid fluid volume (N) as [0.015 × body weight (g)]. Then, we validated it in vivo. Mathematically, the following estimation equation was derived: RBV (%) = 24k / [(Hct1 / Hct2 ) – 1]. For validation, nonongoing haemorrhagic shock was induced in Sprague–Dawley rats by withdrawing 20.0%–60.0% of their total blood volume (TBV) in 5.0% intervals (n = 9). Hct1 was checked after 10 min and normal saline N cc was infused over 10 min. Hct 2 was checked five minutes later. We applied a linear equation to explain RBV (%) with 1 / [(Hct1 / Hct2 ) – 1]. Seven rats losing 30.0%–60.0% of their TBV suffered shock persistently. For them, RBV (%) was updated as 5.67 / [(Hct1 / Hct2 ) – 1] + 32.8 (95% confidence interval [CI] of the slope: 3.14–8.21, p = 0.002, R2 = 0.87). On a Bland-Altman plot, the difference between the estimated and actual RBV was 0.00 ± 4.03%; the 95% CIs of the limits of agreements were included within the pre-determined criterion of validation (< 20%). For rats suffering from persistent, non-ongoing haemorrhagic shock, we derived and validated a simple equation estimating RBV (%). This enables the calculation of blood loss via information on serial haematocrits under a fixed N.Clinical validation is required before utilisation for emergency care of haemorrhagic shock.

PURPOSE: The purpose of this study is to investigate differences in organ-specific cancer incidence according to the region and population size in Korea. MATERIALS AND METHODS: We reviewed the data of the cancer registration program of Gyeongnam Regional Cancer Center between 2008 and 2011. Age-standardized rates of cancer incidence were analyzed according to population size of the region and administrative zone. RESULTS: Incidence of thyroid cancer has been increasing rapidly in both urban and rural areas. However, the thyroid cancer incidence was much lower in rural areas than in urban areas and megalopolis such as Seoul. Gastric cancer was relatively more common in rural areas, in megalopolis near the sea (Ulsan, Busan, and Incheon), and other southern provinces (Chungcheongnam-do, Gyeongsangbuk-do, and Gyeongsangnam-do). A detailed analysis in Gyeongsangnam-do revealed that rural areas have relatively low incidence of thyroid and colorectal cancer, and relatively high incidence of gastric and lung cancer compared to urban areas. CONCLUSION: This study suggests that there are some differences in cancer incidence by population size. Thyroid and colorectal cancer incidence was increasing, and gastric and lung cancer was slightly decreasing in urban areas, whereas gastric and lung cancer incidence still remains high in rural areas.
Busan ; Colorectal Neoplasms ; Epidemiology ; Gyeongsangbuk-do ; Gyeongsangnam-do ; Incidence* ; Korea* ; Lung Neoplasms ; Population Density ; Rural Population ; Seoul ; Stomach Neoplasms ; Thyroid Gland ; Thyroid Neoplasms ; Urbanization

Since the first imported case of Middle East respiratory syndrome coronavirus (MERS-CoV) infection was reported on May 20, 2015 in Korea, there have been 186 laboratory-confirmed cases of MERS-CoV infection with 36 fatalities. Ninety-seven percent (181/186) of the cases had exposure to the health care facilities. We are reporting a superspreading event that transmitted MERS-CoV to 81 persons at a hospital emergency room (ER) during the Korean outbreak in 2015. The index case was a 35-yr-old man who had vigorous coughing while staying at the ER for 58 hr. As in severe acute respiratory syndrome outbreaks, superspreading events can cause a large outbreak of MERS in healthcare facilities with severe consequences. All healthcare facilities should establish and implement infection prevention and control measure as well as triage policies and procedures for early detection and isolation of suspected MERS-CoV cases.
Adult ; Coronavirus Infections/*epidemiology/*virology ; Female ; Humans ; Incidence ; Male ; Middle East Respiratory Syndrome Coronavirus/*isolation & purification ; Pandemics/*statistics & numerical data ; Republic of Korea/epidemiology ; Risk Factors

PURPOSE: Home-based care providers were surveyed to assess the effect of collaborative service between Gyeongnam Regional Cancer Center (GRCC) and public health centers (PHCs) in Gyeongnam province. METHODS: Twenty home-based care providers who had previously participated in the GRCC-PHC care project were recruited from nine PHCs and were surveyed using a questionnaire developed by specialists. Questions were rated using the 5-point Likert scale ranging from "strongly disagree (-2)" to "strongly agree (+2)" and each score was multiplied by the corresponding number of respondents (n=20) with the maximum score of 40. RESULTS: Between January 2008 and December 2011, 73 patients were registered to the collaborative service: 72 by GRCC and one by PHC. Home-based care providers marked the highest score (23 points) to "The collaborative service contributed to patients and their family's psychological stability" and the lowest score (11 points) to "The collaborative service was generally helpful for home-based cancer management." For possible suggestions to improve the service, the highest score (35 points) was given to "Simplification of the hospitalization process" followed by "Substantial benefits for patients at their visit to the hospital" (34 points). CONCLUSION: The results revealed several limitations of the GRCC-PHC collaborative care service for terminal cancer patients. The service could be further improved by developing measures to address the limitations and a service model tailored to region-specific needs.
Academic Medical Centers ; Community Health Centers ; Cooperative Behavior ; Surveys and Questionnaires ; Home Care Services ; Hospitalization ; Humans ; Public Health ; Referral and Consultation ; Specialization

The purpose of this study was to establish a prediction rule for severe illness in adult patients hospitalized with pandemic influenza A (H1N1) 2009. At the time of initial presentation, the baseline characteristics of those with severe illness (i.e., admission to intensive care unit, mechanical ventilation, or death) were compared to those of patients with non-severe illnesses. A total of 709 adults hospitalized with pandemic influenza A (H1N1) 2009 were included: 75 severe and 634 non-severe cases. The multivariate analysis demonstrated that altered mental status, hypoxia (PaO2/FiO2 < or = 250), bilateral lung infiltration, and old age (> or = 65 yr) were independent risk factors for severe cases (all P < 0.001). The area under the ROC curve (0.834 [95% CI, 0.778-0.890]) of the number of risk factors were not significantly different with that of APACHE II score (0.840 [95% CI, 0.790-0.891]) (P = 0.496). The presence of > or = 2 risk factors had a higher sensitivity, specificity, positive predictive value and negative predictive value than an APACHE II score of > or = 13. As a prediction rule, the presence of > or = 2 these risk factors is a powerful and easy-to-use predictor of the severity in adult patients hospitalized with pandemic influenza A (H1N1) 2009.
APACHE ; Adult ; Aged ; Antiviral Agents/therapeutic use ; Female ; Hospitalization ; Humans ; Influenza A Virus, H1N1 Subtype/*isolation & purification ; Influenza, Human/drug therapy/*epidemiology/mortality ; Intensive Care Units ; Male ; Middle Aged ; Pandemics ; Predictive Value of Tests ; ROC Curve ; Respiration, Artificial ; Risk Factors ; Severity of Illness Index

The vast majority of patients with metastatic prostate cancer present with bone metastases and high prostate specific antigen (PSA) level. Rarely, prostate cancer can develop in patients with normal PSA level. Here, we report a patient who presented with a periureteral tumor of unknown primary site that was confirmed as prostate adenocarcinoma after three years with using specific immunohistochemical examination. A 64-year old man was admitted to our hospital with left flank pain associated with masses on the left pelvic cavity with left hydronephrosis. All tumor markers including CEA, CA19-9, and PSA were within the normal range. After an exploratory mass excision and left nephrectomy, the pelvic mass was diagnosed as poorly differentiated carcinoma without specific positive immunohistochemical markers. At that time, we treated him as having a cancer of unknown primary site. After approximately three years later, he revisited the hospital with a complaint of right shoulder pain. A right scapular mass was newly detected with a high serum PSA level (101.7 ng/ml). Tissues from the scapular mass and prostate revealed prostate cancer with positive immunoreactivity for P504S, a new prostate cancer-specific gene. The histological findings were the same as the previous pelvic mass; however, positive staining for PSA was observed only in the prostate mass. This case demonstrates a patient with prostate cancer and negative serological test and tissue staining that turned out to be positive during progression. We suggest the usefulness of newly developed immunohistochemical markers such as P504S to determine the specific primary site of metastatic poorly differentiated adenocarcinoma in men.
Adenocarcinoma ; Flank Pain ; Humans ; Hydronephrosis ; Male ; Neoplasm Metastasis ; Nephrectomy ; Prostate ; Prostate-Specific Antigen ; Prostatic Neoplasms ; Reference Values ; Serologic Tests ; Shoulder Pain ; Biomarkers, Tumor

PURPOSE: Tertiary hyperparathyroidism (tHPT) means a persistent secondary hyperparathyroidism even after successful renal transplantation. Parathyroidectomy (PTX) is an efficient way to treat tHPT. In this study, we reviewed our single center Experience of PTX in regard to postoperative outcomes and analyzed any differences by the types of surgery. METHODS: Among 2,589 recipients who underwent renal allograft between April. 1979 and Dec. 2006, 11 patients (0.4%) were identified to have tHPT and underwent PTX. Levels of intact parathyroid hormone (iPTH) and serum calcium were measured before and after PTX to evaluate therapeutic effect, and serum-creatinine and GFR using the Modification of Diet in Renal Disease (MDRD) equation to investigate any effect to graft function. RESULTS: One patient showed persistent hyperparathyroidism and hypercalcemia after subtotal PTX. We experienced 10 successful PTXs in which 2 total PTX with autotransplantations, 4 subtotal PTXs and 4 limited PTXs. Level of iPTH and serum calcium were at normal range after PTX. Serum creatinine increased and estimated GFR decreased after PTX. Total PTX with autotransplantation showed a tendency of more decrease in the values of iPTH, and GFR after PTX than Subtotal PTX. CONCLUSION: PTX can cure tHPT-specific symptoms and sign by the recovery of hypercalcemia but may carry the risk of deterioration of kidney graft function. Subtotal PTX rather than total PTX might be recommended in the surgical treatment of tHPT to prevent any risk of kidney graft deterioration.
Allografts ; Autografts ; Calcium ; Creatinine ; Diet ; Humans ; Hypercalcemia ; Hyperparathyroidism* ; Hyperparathyroidism, Secondary ; Kidney ; Kidney Transplantation* ; Parathyroid Hormone ; Parathyroidectomy ; Reference Values ; Transplants

PURPOSE: The HSV1-tk reporter gene system is the most widely used system because of its advantage that direct monitoring is possible without the introduction of a separate reporter gene in case of HSV1-tk suicide gene therapy. In this study, we investigate the usefulness of the reporter probe (substrate), 9-(4-[18F]fluoro-3-hydroxymethylbutyl)guanine ([18F]FHBG) for non-invasive reporter gene imaging using PET in HSV1-tk expressing hepatoma model. MATERIALS AND METHODS: Radiolabeled FHBG was prepared in 8 steps from a commercially available triester. The labeling reaction was carried out by NCA nucleophilic substitution with K[18F]/K2.2.2. in acetonitrile using N2-monomethoxytrityl-9-[4-(tosyl)-3-monomethoxytritylmethylbutyl]guanine as a precursor, followed by deprotection with 1 N HCl. Preliminary biological properties of the probe were evaluated with MCA cells and MCA-tk cells transduced with HSV1-tk reporter gene. In vitro uptake and release-out studies of [18F]FHBG were performed, and was analyzed correlation between [18F]FHBG uptake ratio according to increasing numeric count of MCA-tk cells and degree of gene expression. MicroPET scan image was obtained with MCA and MCA-tk tumor bearing Balb/c-nude mouse model. RESULTS: [18F]FHBG was purified by reverse phase semi-HPLC system and collected at around 16-18 min. Radiochemical yield was about 20-25% (corrected for decay), radiochemical purity was >95% and specific activity was around >55.5 GBq/micro mol. Specific accumulation of [18F]FHBG was observed in HSV1-tk gene transduced MCA-tk cells but not in MCA cells, and consecutive 1 hour release-out results showed more than 86% of uptaked [18F]FHBG was retained inside of cells. The uptake of [18F]FHBG was showed a highly significant linear correlation (R2=0.995) with increasing percentage of MCA-tk numeric cell count. In microPET scan images, remarkable difference of accumulation was observed for the two type of tumors. CONCLUSION: [18F]FHBG appears to be a useful as non-invasive PET imaging substrate in HSV1-tk expressing hepatoma model.
Animals ; Carcinoma, Hepatocellular* ; Cell Count ; Gene Expression ; Genes, Reporter ; Genetic Therapy ; Guanine* ; Mice ; Suicide ; Thymidine Kinase

OBJECTIVE: To evaluate the incidence of the +769 G/A mutation of inhibin-alpha gene in Korean patients with idiopathic premature ovarian failure. DESIGN: DNA analysis of the mutation. METHODS: One hundred patients with idiopathic premature ovarian failure (POF) were recruited. Patient with known causes of premature ovarian failure were excluded: cytogenetic abnormalities, prior chemotherapy, prior bilateral oophorectomy and autoimmune disease, etc. DNA was extracted from peripheral blood and the +769 G/A variant of Inhibin-alpha gene (INH-alpha) was analyzed by polymerase chain reaction (PCR) and restriction fragment length polymorphism using restriction enzyme BbvI. RESULTS: We didn't find any case of +769 G/A variant in Inhibin-alpha gene in 100 Korean patients with idiopathic POF. CONCLUSION: This result suggests that in contrary to the recent data reported on the Asian population, the +769 G/A variant in inhibin-alpha gene may not exist in Korean patients with idiopathic POF.
Asian Continental Ancestry Group ; Autoimmune Diseases ; Chromosome Aberrations ; DNA ; Drug Therapy ; Female ; Humans ; Incidence ; Ovariectomy ; Polymerase Chain Reaction ; Polymorphism, Restriction Fragment Length ; Primary Ovarian Insufficiency*