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.

BACKGROUND: Although deferasirox (DFX) is reported to have anti-tumor effects, its anti-leukemic activity remains unclear. We evaluated the effect of DFX treatment on two murine lymphoid leukemia cell lines, and clarified the mechanisms underlying its potential anti-leukemic activity. METHODS: L1210 and A20 murine lymphoid leukemia cell lines were treated with DFX. Cell viability and apoptosis were evaluated by the 3-(4,5-dimethylthaizol-2-yl)-5-(3-carboxymethylphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay and fluorescence-activated cell sorting (FACS) analysis, respectively. Immunoblotting was performed to detect the expression of key apoptotic proteins. RESULTS: In dose- and time-dependent manner, DFX decreased viability and increased apoptosis of murine leukemic cells. Fas expression was significantly higher in A20 cells than in L1210 cells at all DFX concentrations tested. Although both cell lines exhibited high caspase 3 and caspase 9 expression, a critical component of the intrinsic mitochondrial apoptotic pathway, expression was greater in L1210 cells. In contrast, caspase 8, a key factor in the extrinsic apoptotic pathway, showed greater expression in A20 cells. Cytochrome c expression was significantly higher in L1210 cells. In both cell lines, co-treatment with ferric chloride and DFX diminished the expression of these intracellular proteins, as compared to DFX treatment alone. CONCLUSION: Treatment with DFX increased caspase-dependent apoptosis in two murine lymphoid leukemia cell lines, with differing apoptotic mechanisms in each cell line.
Apoptosis* ; Caspase 3 ; Caspase 8 ; Caspase 9 ; Cell Line* ; Cell Survival ; Cytochromes c ; Flow Cytometry ; Immunoblotting ; Leukemia* ; Leukemia, Lymphoid

PURPOSE: To evaluate the treatment outcome and prognostic factor of postoperative radiotherapy for extremity soft tissue sarcoma (STS). MATERIALS AND METHODS: Forty three patients with extremity STS were treated with conservative surgery and postoperative radiotherapy from January 1981 to December 2010 at Korea University Medical Center. Median total 60 Gy (range, 50 to 74.4 Gy) of radiation was delivered and 7 patients were treated with chemotherapy. RESULTS: The median follow-up period was 70 months (range, 5 to 302 months). Twelve patients (27.9%) sustained relapse of their disease. Local recurrence occurred in 3 patients (7.0%) and distant metastases developed in 10 patients (23.3%). The 5-year overall survival (OS) was 69.2% and disease free survival was 67.9%. The 5-year local relapse-free survival was 90.7% and distant relapse-free survival was 73.3%. On univariate analysis, no significant prognostic factors were associated with development of local recurrence. Histologic grade (p = 0.005) and stage (p = 0.02) influenced the development of distant metastases. Histologic grade was unique significant prognostic factor for the OS on univariate and multivariate analysis. Severe acute treatment-related complications, Common Terminology Criteria for Adverse Events (CTCAE) grade 3 or 4, developed in 6 patients (14.0%) and severe late complications in 2 patients (4.7%). CONCLUSION: Conservative surgery with postoperative radiotherapy achieved a satisfactory rate of local control with acceptable complication rate in extremity STS. Most failures were distant metastases that correlate with tumor grade and stage. The majority of local recurrences developed within the field. Selective dose escalation of radiotherapy or development of effective systemic treatment might be considered.
Academic Medical Centers ; Disease-Free Survival ; Extremities ; Follow-Up Studies ; Humans ; Korea ; Multivariate Analysis ; Neoplasm Metastasis ; Recurrence ; Sarcoma ; Treatment Outcome

BACKGROUND: Therapeutic hypothermia has been recommended as a standard treatment of cardiac arrest patients after return of spontaneous circulation. There are various methods to drop patient's core body temperature below 33.5degrees C. We compared the cooling rate of the conventional cooling method using cold saline bladder irrigation with the commercial hydrogel pad in out-of-hospital cardiac arrest (OHCA) patients. METHODS: We collected data retrospectively from the Samsung Medical Center hypothermia database. The conventional method group was cooled with IV infusion of 2,000 ml of 4degrees C cold saline and cold saline bladder irrigation. Patients in the hydrogel pad group had their body temperature lowered with the Artic Sun(R) after receiving 2,000 ml of 4degrees C cold saline intravenously. The induction time was defined as time from cold saline infusion to the esophageal core temperature below 33.5degrees C. The esophageal temperature probe insertion to the target temperature time (ET to target BT time) was defined as the time from the esophageal probe insertion to the core temperature below 33.5degrees C. We compared these times and cooling rates between the two groups. RESULTS: Eighty one patients were enrolled. Fifty seven patients were included in the hydrogel pad group and 24 patients were in the conventional group. There were no statistical differences of baseline characteristics between the two groups. The induction time of the conventional group (138 min., IQR 98-295) was shorter than that of the hydrogel pad group (190 min., IQR 140-250). The ET to target BT time of the conventional group (106 min., IQR 68-249) was shorter than that of the hydrogel pad group (163 min., IQR 108-222). The cooling rate of the conventional group (0.93degrees C/hr., IQR 0.58-2.08) was lower than that of the hydrogel pad group (1.05degrees C/hr., IQR 0.74-1.96). However, there were no statistical differences in the induction time, the ET to target BT time and the cooling rate between the two groups. CONCLUSIONS: There was no significant statistical difference of the cooling rate of the hydrogel pad and conventional method on the induction time of therapeutic hypothermia in Patients with OHCA. The conventional cooling method can be used as an effective and efficient way to lower OHCA patient's core body temperature during the induction phase of therapeutic hypothermia.
Body Temperature ; Cold Temperature ; Heart Arrest ; Humans ; Hydrogel ; Hypothermia ; Out-of-Hospital Cardiac Arrest ; Retrospective Studies ; Urinary Bladder

PURPOSE: To evaluate long-term local control rate and toxicity in patients treated with external beam radiotherapy (EBRT) for pituitary adenomas. MATERIALS AND METHODS: We retrospectively reviewed the medical records of 60 patients treated with EBRT for pituitary adenoma at Korea University Medical Center from 1996 and 2006. Thirty-five patients had hormone secreting tumors, 25 patients had non-secreting tumors. Fifty-seven patients had received postoperative radiotherapy (RT), and 3 had received RT alone. Median total dose was 54 Gy (range, 36 to 61.2 Gy). The definition of tumor progression were as follows: evidence of tumor progression on computed tomography or magnetic resonance imaging, worsening of clinical sign requiring additional operation or others, rising serum hormone level against a previously stable or falling value, and failure of controlling serum hormone level so that the hormone level had been far from optimal range until last follow-up. Age, sex, hormone secretion, tumor extension, tumor size, and radiation dose were analyzed for prognostic significance in tumor control. RESULTS: Median follow-up was 5.7 years (range, 2 to 14.4 years). The 10-year actuarial local control rates for non-secreting and secreting adenomas were 96% and 66%, respectively. In univariate analysis, hormone secretion was significant prognostic factor (p = 0.042) and cavernous sinus extension was marginally significant factor (p = 0.054) for adverse local control. All other factors were not significant. In multivariate analysis, hormone secretion and gender were significant. Fifty-three patients had mass-effect symptoms (headache, dizziness, visual disturbance, hypopituitarism, loss of consciousness, and cranial nerve palsy). A total of 17 of 23 patients with headache and 27 of 34 patients with visual impairment were improved. Twenty-seven patients experienced symptoms of endocrine hypersecretion (galactorrhea, amenorrhea, irregular menstruation, decreased libido, gynecomastia, acromegaly, and Cushing's disease). Amenorrhea was abated in 7 of 10 patients, galactorrhea in 8 of 8 patients, acromegaly in 7 of 11 patients, Cushing's disease in 4 of 4 patients. Long-term complication was observed in 4 patients; 3 patients with cerebrovascular accident, 1 patient developed dementia. Of these patients, 3 of 4 received more than 60 Gy of irradiation. CONCLUSION: EBRT is highly effective in preventing recurrence and reducing mass effect of non-secreting adenoma. Effort to improve tumor control of secreting adenoma is required. Careful long-term follow-up is required when relatively high dose is applied. Modern radiosurgery or proton RT may be options to decrease late complications.
Academic Medical Centers ; Acromegaly ; Adenoma ; Amenorrhea ; Cavernous Sinus ; Cranial Nerves ; Dementia ; Dizziness ; Female ; Follow-Up Studies ; Galactorrhea ; Gynecomastia ; Headache ; Humans ; Hypopituitarism ; Korea ; Libido ; Magnetic Resonance Imaging ; Male ; Medical Records ; Menstruation ; Multivariate Analysis ; Pituitary Neoplasms ; Pregnancy ; Protons ; Radiosurgery ; Recurrence ; Retrospective Studies ; Stroke ; Unconsciousness ; Vision Disorders

Authors performed extrapedicular screws fixation in thoracic spines. Because patient had very narrow thoracic pedicles, classical transpedicular screws fixation could not be accomplished. In case of narrow thoracic pedicles, extrapedicular screws fixation would be a good alternative technique. We describe here a method for thoracic extrapedicular screws fixation.
Humans ; Spine

OBJECTIVE: Spontaneous intracerebral hemorrhage (sICH) is a leading cause of morbidity and mortality, especially in Asian countries. Nevertheless, few reports of sICH in young people have been published. This study investigates the clinical features of sICH in young people. METHODS: Between February 1999 and December 2007, we retrospectively reviewed the medical records of patients aged 45 years diagnosed with sICH at our institute. We analyzed the causes, locations, risk factors, and final outcomes of sICH in these patients. RESULTS: Twenty-one patients (14.5%) were younger than 25 years, while 27 patients (18.6%) were 25~34 years old. Ninety-seven patients (66.9%) were between the ages of 35~45. The most common cause of sICH was hypertension (57.9%). The most common location of sICH was in the lobar region (35.2%). Vascular anomaly was the main cause in both the <25 age group (76.2%) and the 25~34 age group (70.4%). The diagnostic rate of angiography was 75% for the under 25 age group and 80% in the 25~34 age group. CONCLUSIONS: Hypertension is the most common cause of sICH in people between 35 and 45, and vascular anomaly is the main cause in people under 35 years of age. Thus, angiography should be mandatory for people under 35 with sICH, and for people with lobar hemorrhage. For young people, early diagnosis of hypertension and strict blood pressure control is recommended.
Aged ; Angiography ; Asian Continental Ancestry Group ; Blood Pressure ; Cerebral Hemorrhage ; Early Diagnosis ; Hemorrhage ; Humans ; Hypertension ; Medical Records ; Retrospective Studies ; Risk Factors

The aims of this study were to verify the hypoxia-reoxygenation injury of primary cultured Kupffer cells and the effect of propofol against the hypoxia-reoxygenation injury through quantitating lactate dehydrogenase (LDH) release and superoxide dismutase (SOD) activity.The sequential treatments with hypoxia and reoxygenation induced significant increasement of LDH release (P.0.01) and decresement of SOD activity(P.0.05) in primary cultured Kupffer cell. The level of LDH release and SOD activity after sequential treatments with hypoxia and reoxygenation were restored to the control level by the propofol treatment in the concentration of 0.5 and 5 microgram/mL. Propofol in concentration of 50 microgram/mL induced significant increasement of LDH release (P.0.01) on both normal culture and hypoxia-reoxygenation culture of the Kupffer cell. As hypoxia and reoxygenation procedures and propofol treatment were concurrently added to the cultured Kupffer cell, propofol treatment in the concentration of 50 microgram/mL decreased significantly the SOD activity (P.0.01). In conclusion, propofol in this hypoxia-reoxygenation model could provide a valuable clue for the study of liver transplantation and of propofol.
Anoxia ; Kupffer Cells ; L-Lactate Dehydrogenase ; Liver Transplantation ; Propofol* ; Superoxide Dismutase* ; Superoxides*

BACKGROUND: In the milieu of the postischemic nerve system, oxygen plays an important, but different role on the ischemia/reperfusion injury. Oxygen is needed in newly restored oxidative phosphorylation to reenergize neurons depleted of ATP and membrane potential. Alternatively, oxygen may also be used as substrate for the destructive free radical-mediated processes that seem to be common final pathways in numerous mechanisms of ischemia/reperfusion injury. Several investigators have reported decreasing inspired oxygen concentration was neuroprotective. But, others have demonstrated hyperbaric oxygen was useful for reducing the ischemia/reperfusion injury. Our study aims first to evaluate the effects of difference in arterial oxygen tension on early phase of ischemia/reperfusion injury and to outline practical use of oxygen to reduce ischemic/reperfusion injury. METHODS: A rabbit spinal cord ischemia model of infrarenal aortic occlusion for 17 mins was employed. Rabbits were randomly assigned to three groups. The rabbits in control group (n = 3) did not undergo ischemic insult. The rabbits in group A (n = 5) and B (n = 5) underwent ischemic insult for 17 mins and then breathed oxygen (6 L/min) via facial mask or room air, respectively. We observed neurologic function for 2 days. The sections of the spinal cords were stained with hematoxylin and eosin, and the number of spinal motor neurons in ventral region was counted by light microscopy. RESULTS: All rabbits in control group did not have neurologic dysfunction whereas all rabbits in group A and B had neurologic dysfunction at same degree. Spinal motor neurons in ventral gray matter in group A and B decreased significantly compared with those in control group (P < 0.05). But, difference in number between group A and B was not significant. CONCLUSIONS: The result indicated that the level of arterial oxygen tension within the clinical range had little effect on early phase of ischemia/reperfusion injury.
Adenosine Triphosphate ; Eosine Yellowish-(YS) ; Hematoxylin ; Humans ; Masks ; Membrane Potentials ; Microscopy ; Motor Neurons ; Neurologic Manifestations ; Neurons ; Oxidative Phosphorylation ; Oxygen* ; Rabbits* ; Research Personnel ; Spinal Cord Ischemia ; Spinal Cord*

Percutaneous pericardiocentesis guided by two-dimensional echocardiography was introduced in 1983 as an alternative to electrocardiographically or fluoroscopically guided puncture for the management of pericardial effusion. The objective of this study was to investigate echocardiographically (echo) - guided pericardiocenteses performed at Yonsei Cardiovascular Center from January 1, 1993 to December 31, 2003, and also to determine whether patient profiles, etiology, and practice patterns have changed over this 11-year period. The medical records of 272 patients were examined and a follow-up survey was conducted. Patient clinical profiles, etiology, echocardiographic findings, and procedural details were determined for 2 periods: January, 1993 through December, 1997 (period 1) ; and January 1998 through December, 2003 (period 2). During the 11-year study period, 291 therapeutic, echo-guided pericardiocenteses with pericardial catheter drainage were performed in 272 patients. The number of pericardiocentesis in period 2 was increased compared with period 1 (191 cases vs. 100 cases). The mean age at pericardiocentesis increased from 49 +/-17 years in period 1 to 55+/-16 years in period 2 (p< 0.05). The procedural success rate was 99% overall with a major complication rate of 0.7% (2 cases of right ventricular free wall perforation which required emergency operation). Only one procedure-related mortality (< 30 days) was noted. Malignancy was the leading cause of a pericardial effusion requiring pericardiocentesis (45.6%). The incidence of pericardial effusion following cardiothoracic surgery and percutaneous coronary intervention procedures accounted for nearly 20% of all pericardiocenteses performed. Echo-guided pericardiocentesis has become a safe, standard practice for clinically significant pericardial effusion, in line with the changes of patients profiles over the 11 years of the study.
Adult ; Aged ; Cardiac Tamponade/therapy/ultrasonography ; Drainage ; *Echocardiography ; Female ; Human ; Male ; Middle Aged ; Pericardial Effusion/*therapy/*ultrasonography ; Pericardiocentesis/adverse effects/*methods ; Retrospective Studies ; Treatment Outcome