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.

Crohn's disease (CD) may involve any part of the gastrointestinal tract, from the mouth to the anus. Approximately >90% of cases occur in the small bowel and colon. Upper gastrointestinal involvement, especially duodenal manifestation, is relatively rare. Therefore, adequate medical treatment for duodenal CD has not yet been established. We report a case of CD with duodenal involvement. A 46-year-old man with Crohn's ileocolitis presented to our hospital with right upper quadrant pain. An endoscopy showed a deep excavated ulcer with deformity at the duodenal bulb, and he was initially treated with azathioprine (1 mg/kg), Pentasa (3.0 g/day), and a proton pump inhibitor for 1 year. However, the deep ulcer did not heal. Therefore, infliximab infusion therapy was initiated, and the duodenal lesion completely resolved on follow-up esophagogastroduodenoscopy. We report a case of duodenal CD that completely resolved following infliximab infusion, with a review of the literature.
Anal Canal ; Azathioprine ; Colon ; Congenital Abnormalities ; Crohn Disease* ; Duodenum ; Endoscopy ; Endoscopy, Digestive System ; Follow-Up Studies ; Gastrointestinal Tract ; Humans ; Infliximab ; Mesalamine ; Middle Aged ; Mouth ; Proton Pumps ; Ulcer

BACKGROUND/AIMS: Carnitine and vitamin complex (Godex(R)) is widely used in patients with chronic liver disease who show elevated liver enzyme in South Korea. The purpose of this study is to identify the efficacy and safety of carnitine from entecavir combination therapy in Alanine aminotransferase (ALT) elevated Chronic Hepatitis B (CHB) patients. METHODS: 130 treatment-naive patients with CHB were enrolled from 13 sites. The patients were randomly selected to the entecavir and the complex of entecavir and carnitine. The primary endpoint of the study is ALT normalization level after 12 months. RESULTS: Among the 130 patients, 119 patients completed the study treatment. The ALT normalization at 3 months was 58.9% for the monotherapy and 95.2% for the combination therapy (P<0.0001). ALT normalization rate at 12 months was 85.7% for the monotherapy and 100% for the combination group (P=0.0019). The rate of less than HBV DNA 300 copies/mL at 12 months was not statistically significant (P=0.5318) 75.9% for the monotherapy, 70.7% for the combination and it was. Quantification of HBsAg level was not different from the monotherapy to combination at 12 months. Changes of ELISPOT value to evaluate the INF-gamma secretion by HBsAg showed the increasing trend of combination therapy compare to mono-treatment. CONCLUSIONS: ALT normalization rate was higher in carnitine complex combination group than entecavir group in CHB. Combination group was faster than entecavir mono-treatment group on ALT normalization rate. HBV DNA normalization rate and the serum HBV-DNA level were not changed by carnitine complex treatment.
Adult ; Alanine Transaminase/blood ; Antiviral Agents/*therapeutic use ; Carnitine/*therapeutic use ; DNA, Viral/analysis ; Drug Therapy, Combination ; Enzyme-Linked Immunospot Assay ; Female ; Guanine/*analogs & derivatives/therapeutic use ; Hepatitis B Surface Antigens/blood ; Hepatitis B e Antigens/blood ; Hepatitis B virus/genetics ; Hepatitis B, Chronic/*drug therapy ; Humans ; Interferon-gamma/metabolism ; Male ; Middle Aged ; Mitochondria/physiology ; Treatment Outcome ; Vitamin B Complex/*therapeutic use

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

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

BACKGROUND: Dendritic cell (DC)-based vaccines are currently being evaluated as a novel strategy for tumor vaccination and immunotherapy. However, inducing long-term regression in established tumor-implanted mice is difficult. Here, we show that deoxypohophyllotoxin (DPT) induces maturation and activation of bone marrow-derived DCs via Toll-like receptor (TLR) 4 activation of MAPK and NF-kappaB. METHODS: The phenotypic and functional maturation of DPT-treated DCs was assessed by flow cytometric analysis and cytokine production, respectively. DPT-treated DCs was also used for mixed leukocyte reaction to evaluate T cell-priming capacity and for tumor regression against melanoma. RESULTS: DPT promoted the activation of CD8+ T cells and the Th1 immune response by inducing IL-12 production in DCs. In a B16F10 melanoma-implanted mouse model, we demonstrated that DPT-treated DCs (DPT-DCs) enhance immune priming and regression of an established tumor in vivo. Furthermore, migration of DPT-DCs to the draining lymph nodes was induced via CCR7 upregulation. Mice that received DPT-DCs displayed enhanced antitumor therapeutic efficacy, which was associated with increased IFN-gamma production and induction of cytotoxic T lymphocyte activity. CONCLUSION: These findings strongly suggest that the adjuvant effect of DPT in DC vaccination is associated with the polarization of T effector cells toward a Th1 phenotype and provides a potential therapeutic antitumor immunity.
Animals ; Dendritic Cells ; Immunotherapy ; Interleukin-12 ; Lymph Nodes ; Lymphocyte Culture Test, Mixed ; Lymphocytes ; Mice ; Phenotype ; Podophyllotoxin ; T-Lymphocytes ; Toll-Like Receptors ; Up-Regulation ; Vaccination ; Vaccines

OBJECTIVE: Juvenile rheumatoid arthritis (JRA) is classified as polyarticular, oligoarticular, and systemic onset type by clinical symptoms presented during first six months. This study was performed to investigate the clinical features and course of systemic onset JRA. METHODS: We performed a retrospective study for patients who were diagnosed as JRA between March 2000 and March 2006 according to the JRA criteria of the International League of Association for Rheumatology (ILAR). RESULTS: Of the 216 JRA patients, 33 patients (11 male/ 22 female) were systemic onset type. Because of insufficient data, 6 patients were excluded. Chief complaints at the time of diagnosis were fever (81.5%) and arthralgia (77.7%). During the disease course, all patients manifested fever and arthritis, rash (59.2%) and splenomegaly (22.2%) also occurred. Most patients had symmetric (81.5%) arthritis, and involved more than five joints (59.3%) including knee and wrist. Anemia, leukocytosis, and thrombocytosis were common laboratory abnormalities. Almost all patients had elevated level of C-reactive protein and erythrocyte sediment rate. Some patients had positive results about immunologic marker such as rheumatoid factor (3.8%), antinuclear antibody (57.7%), and antiperinuclear factor (9.5%). Therapeutic regimens included glucocorticoids (88.9%), nonsteroidal anti-inflammatory drugs (81.5%), methotrexate (81.5%), and hydroxychloroquine (55.6%). Biologic agents were applied in 5 patients, and 3 showed improvement of disease activity. Combination therapy was introduced in 18.5% of patients, and 63% of patients still required medications. CONCLUSION: In Korea, systemic onset JRA patients had variable clinical manifestations and chronic course of disease, which often extended into adulthood.
Anemia ; Antibodies, Antinuclear ; Arthralgia ; Arthritis ; Arthritis, Juvenile* ; Biological Factors ; Biomarkers ; C-Reactive Protein ; Diagnosis ; Erythrocytes ; Exanthema ; Fever ; Glucocorticoids ; Humans ; Hydroxychloroquine ; Joints ; Knee ; Korea ; Leukocytosis ; Methotrexate ; Retrospective Studies ; Rheumatoid Factor ; Rheumatology ; Splenomegaly ; Thrombocytosis ; Wrist

PURPOSE: To assess the current status of endourology and laparoscopy in Korea. MATERIALS AND METHODS: Using the database directory of the Korean Urological Association, 83 urology training hospitals were identified. A detailed questionnaire was designed and sent by post and e-mail. The questionnaire included questions regarding the number of various endourological and laparoscopic procedures between 1998 and 2002. The questionnaires of those responding were analyzed. RESULTS: Responses were received from 45 hospitals (response rate 54.2%). 133 antegrade and 626 retrograde endourological procedures for urinary strictures were performed during the period of the study in 12 and 35 hospitals, respectively. 42 hospitals (93.3%) were performing shock wave lithotripsy for urinary stone disease. 29 hospitals (64.4%) reported having performed more than one laparoscopic procedure during the five years. The annual total numbers of laparoscopic procedures increased from 217 in 1998 to 725 in 2002. Simple laparoscopic nephrectomy was the most widely accepted procedure, and was being performed in 18 hospitals. Laparoscopic adrenalectomy, radical nephrectomy, diagnostic laparoscopy, laparoscopic renal cyst marsupialization, nephroureterectomy and donor nephrectomy were performed in more than 10 hospitals. However, the actual number of laparoscopic procedures was limited in most hospitals. More than 40 laparoscopic procedures per year were performed by only four hospitals. CONCLUSIONS: This survey revealed an increasing number of endourological and laparoscopic procedures. However, laparoscopy seems to be mainly a larger hospital-based technology in Korea. These results can be utilized as fundamental data for establishing future developmental requirements of endourology and laparoscopy in Korea.
Adrenalectomy ; Constriction, Pathologic ; Electronic Mail ; Endoscopy ; Humans ; Korea ; Laparoscopy* ; Lithotripsy ; Nephrectomy ; Surveys and Questionnaires ; Shock ; Surgical Procedures, Minimally Invasive ; Tissue Donors ; Urinary Calculi ; Urology*

Pulmonary alveolar proteinosis(PAP) is a disorder in which an insoluble, proteinaceous material, rich in phospholipids, is deposited in the alveoli and bronchioles. The deficiency in the clearance and degradation of the i ntra-alveolar phospholipoproteinaceous material in PAP most likely represents a dysfunction of the type II pneumocytes. Although the pathogenesis and causative treatment of PAP is unclear a whole lung bronchopulmonary lavage is a relatively safe and effective treatment. Here we experienced a case of pulmonary alveolar proteinosis in a 62 year old female patient who had pulmonary tuberculosis approximately 20 years ago. She complained of aggravated dyspnea and chronic cough, and presented fine inspiratory crackles at both lung fields. diffuse ground glass opacity with some area of consolidation and smooth interlobular septal thickenings in both upper, right middle lobes, and a portion of right lower lobe. Optical microscopy of the lung tissue obtained by an open lung biopsy many granulomas containing acid-fast smear positive bacilli and diffuse homogeneous PAS-positive fluid in the alveolar space. Immunohistochemical stain showed surfactant A in the alveolar space. Antituberculosis drugs with bronchoalveolar lavage were used to treat the disease. There after she showed improvement in her symptoms and a partial improvement in the chest X-ray and HRCT findings. We present a case of PAT associated with pulmonary tuberculosis.
Biopsy ; Bronchioles ; Bronchoalveolar Lavage ; Cough ; Dyspnea ; Female ; Glass ; Granuloma ; Humans ; Lung ; Microscopy ; Middle Aged ; Phospholipids ; Pneumocytes ; Pulmonary Alveolar Proteinosis* ; Respiratory Sounds ; Thorax ; Tuberculosis, Pulmonary*

Pulmonary alveolar proteinosis(PAP) is a disorder in which an insoluble, proteinaceous material, rich in phospholipids, is deposited in the alveoli and bronchioles. The deficiency in the clearance and degradation of the i ntra-alveolar phospholipoproteinaceous material in PAP most likely represents a dysfunction of the type II pneumocytes. Although the pathogenesis and causative treatment of PAP is unclear a whole lung bronchopulmonary lavage is a relatively safe and effective treatment. Here we experienced a case of pulmonary alveolar proteinosis in a 62 year old female patient who had pulmonary tuberculosis approximately 20 years ago. She complained of aggravated dyspnea and chronic cough, and presented fine inspiratory crackles at both lung fields. diffuse ground glass opacity with some area of consolidation and smooth interlobular septal thickenings in both upper, right middle lobes, and a portion of right lower lobe. Optical microscopy of the lung tissue obtained by an open lung biopsy many granulomas containing acid-fast smear positive bacilli and diffuse homogeneous PAS-positive fluid in the alveolar space. Immunohistochemical stain showed surfactant A in the alveolar space. Antituberculosis drugs with bronchoalveolar lavage were used to treat the disease. There after she showed improvement in her symptoms and a partial improvement in the chest X-ray and HRCT findings. We present a case of PAT associated with pulmonary tuberculosis.
Biopsy ; Bronchioles ; Bronchoalveolar Lavage ; Cough ; Dyspnea ; Female ; Glass ; Granuloma ; Humans ; Lung ; Microscopy ; Middle Aged ; Phospholipids ; Pneumocytes ; Pulmonary Alveolar Proteinosis* ; Respiratory Sounds ; Thorax ; Tuberculosis, Pulmonary*