Background: We investigated whether distance max , that is, the degree of distance between the upper aerodigestive tract (UAT) mass and the farthest pathologic lymph node, was significantly associated with survival in patients with limited-stage UAT natural killer/T cell lymphoma (NKTCL). Methods: A total of 157 patients who received chemotherapy (CTx) with/without radiotherapy (RTx) were enrolled. Results: In the survival analysis, an elevated lactate dehydrogenase level [progression-free survival (PFS): hazard ratio (HR), 2.948; 95% confidence interval (CI), 1.606‒5.404; P ＜0.001; overall survival (OS): HR, 2.619; 95% CI, 1.594‒4.822; P =0.003], short distance max (PFS: HR, 0.170; 95% CI, 0.071‒0.410; P ＜0.001; OS: HR, 0.142; 95% CI, 0.050‒0.402; P ＜ 0.001), and CTx combined with RTx (HR, 0.168; 95%CI, 0.079‒0.380; P < 0.001; OS: HR, 0.193; 95% CI, 0.087‒0.429; P ＜0.001) had an independent predictive value for PFS and OS. Conclusion The evaluation of the degree of lymphatic spread and local control by CTx combined with RTx is essential in patients with limited-stage UAT NKTCL.

Background: We investigated whether distance max , that is, the degree of distance between the upper aerodigestive tract (UAT) mass and the farthest pathologic lymph node, was significantly associated with survival in patients with limited-stage UAT natural killer/T cell lymphoma (NKTCL). Methods: A total of 157 patients who received chemotherapy (CTx) with/without radiotherapy (RTx) were enrolled. Results: In the survival analysis, an elevated lactate dehydrogenase level [progression-free survival (PFS): hazard ratio (HR), 2.948; 95% confidence interval (CI), 1.606‒5.404; P ＜0.001; overall survival (OS): HR, 2.619; 95% CI, 1.594‒4.822; P =0.003], short distance max (PFS: HR, 0.170; 95% CI, 0.071‒0.410; P ＜0.001; OS: HR, 0.142; 95% CI, 0.050‒0.402; P ＜ 0.001), and CTx combined with RTx (HR, 0.168; 95%CI, 0.079‒0.380; P < 0.001; OS: HR, 0.193; 95% CI, 0.087‒0.429; P ＜0.001) had an independent predictive value for PFS and OS. Conclusion The evaluation of the degree of lymphatic spread and local control by CTx combined with RTx is essential in patients with limited-stage UAT NKTCL.

Mitochondrial targeting is a promising approach for solving current issues in clinical application of chemotherapy and diagnosis of several disorders. Here, we discuss direct conjugation of mitochondrial-targeting moieties to anticancer drugs, antioxidants and sensor molecules. Among them, the most widely applied mitochondrial targeting moiety is triphenylphosphonium (TPP), which is a delocalized cationic lipid that readily accumulates and penetrates through the mitochondrial membrane due to the highly negative mitochondrial membrane potential. Other moieties, including short peptides, dequalinium, guanidine, rhodamine, and F16, are also known to be promising mitochondrial targeting agents. Direct conjugation of mitochondrial targeting moieties to anticancer drugs, antioxidants and sensors results in increased cytotoxicity, anti-oxidizing activity and sensing activity, respectively, compared with their non-targeting counterparts, especially in drug-resistant cells. Although many mitochondria-targeted anticancer drug conjugates have been investigated and , further clinical studies are still needed. On the other hand, several mitochondria-targeting antioxidants have been analyzed in clinical phases I, II and III trials, and one conjugate has been approved for treating eye disease in Russia. There are numerous ongoing studies of mitochondria-targeted sensors.

No abstract available.
Female ; Fusion Proteins, bcr-abl/*genetics ; Humans ; Male ; Middle Aged ; Mutation ; Myeloproliferative Disorders/*genetics ; Polycythemia Vera/genetics ; Primary Myelofibrosis/genetics ; Proteins/*genetics ; Thrombocythemia, Essential/genetics

BACKGROUND: It is widely known that the prognosis of acute myeloid leukemia (AML) depends on chromosomal abnormalities. The majority of AML patients relapse and experience a dismal disease course despite initial remission. METHODS: We reviewed the medical records and laboratory findings of 55 AML patients who had relapsed between 2004 and 2013 and who had been treated at the Division of Hematology of the Pusan National University Hospital. RESULTS: The event-free survival (EFS) was related to prognostic karyotype classification at the time of diagnosis and relapse (unfavorable vs. favorable or intermediate karyotypes at diagnosis, 8.2 vs. 11.9 mo, P=0.003; unfavorable vs. favorable or intermediate karyotypes at relapse, 8.2 vs. 11.9 mo, P=0.009). The overall survival (OS) was significantly correlated with karyotype classification only at diagnosis (unfavorable vs. favorable or intermediate vs. karyotypes at diagnosis, 8.5 vs. 21.8 mo, P=0.001; unfavorable vs. favorable or intermediate karyotypes at relapse, 8.5 vs. 21.2 mo, P=0.136). A change in karyotype between diagnosis and relapse, which is regarded as a factor of resistance against treatment, was not a significant prognostic factor for OS, EFS, and post-relapse survival (PRS). A Cox proportional hazards model showed that the combined use of fludarabine, cytosine arabinoside, and granulocyte colony-stimulating factor (FLAG) as a salvage regimen, was a significant prognostic factor for OS (hazard ratio=0.399, P=0.010) and the PRS (hazard ratio=0.447, P=0.031). CONCLUSION: The karyotype classification at diagnosis predicts survival including PRS in relapsed AML patients as well as in treatment-naïve patients. We suggest that presently, administration of salvage FLAG could be a better treatment option.
Busan ; Chromosome Aberrations ; Classification ; Clonal Evolution* ; Cytarabine ; Diagnosis ; Disease-Free Survival ; Granulocyte Colony-Stimulating Factor ; Hematology ; Humans ; Karyotype ; Leukemia, Myeloid, Acute ; Medical Records ; Prognosis ; Proportional Hazards Models ; Recurrence

We evaluated the incidence, clinical characteristics, and prognostic impact of calreticulin (CALR) mutations in essential thrombocythemia (ET) and primary myelofibrosis (PMF) patients. In all, 48 ET and 14 PMF patients were enrolled, and the presence of CALR mutations was analyzed by direct sequencing. Patients were classified into three subgroups according to Janus kinase 2 (JAK2) V617F and CALR mutation status, and their clinical features and prognosis were compared. CALR mutations were detected in 15 (24.2%) patients, and the incidence increased to 50.0% in 30 JAK2 V617F mutation-negative cases. These included 11 patients with three known mutations (c.1092_1143del [seven cases], c.1154_1155insTTGTC [three cases], and c.1102_1135del [one case]) and 4 patients with novel mutations. ET patients carrying CALR mutation were younger, had lower white blood cell counts, and experienced less thrombosis during follow-up than those carrying JAK2 V617F mutation, while both patient groups showed similar clinical features and prognosis. In ET patients without JAK2 V617F mutation, CALR mutation did not significantly affect clinical manifestation and prognosis. In conclusion, CALR mutation analysis could be a useful diagnostic tool for ET and PMF in 50% of the cases without JAK2 V617F mutations. The prognostic impact of CALR mutations needs further investigation.
Adult ; Aged ; Calreticulin/*genetics ; DNA Mutational Analysis ; Exons ; Female ; Genotype ; Humans ; INDEL Mutation ; Janus Kinase 2/genetics ; Male ; Middle Aged ; Primary Myelofibrosis/diagnosis/epidemiology/*genetics ; Prognosis ; Republic of Korea ; Tertiary Care Centers ; Thrombocythemia, Essential/diagnosis/epidemiology/*genetics ; Young Adult

BACKGROUND: To identify potential molecular prognostic markers in core binding factor (CBF) AML, we analyzed incidences and prognostic impacts of mutations in c-KIT, WT1, CEBPA, CBL, and a number of epigenetic genes in CBF AML. METHODS: Seventy one and 21 AML patients with t(8;21) and inv(16) were enrolled in this study, respectively. NPM1, CEBPA, c-KIT, IDH1/2, DNMT3A, EZH2, WT1, and CBL mutations were analyzed by direct sequencing. Patients were categorized with respect to c-KIT and WT1 mutation status, and both clinical features and prognoses were compared. RESULTS: The incidences of FLT3 internal tandem duplication (ITD), NPM1, CEBPA, IDH1/2, DNMT3A, EZH2, and CBL mutations were low (< or =5%) in CBF AML patients. However, c-KIT and WT1 mutations occurred frequently (10.9% and 13.8%, respectively). t(8;21) patients with c-KIT mutations showed significantly shorter overall survival (OS) and disease free survival (DFS) periods than those without mutations (P<0.001, for both); however, although the limited number of t(8;21) patients were analyzed, WT1 mutation status did not affect prognosis significantly. Relapse or death during follow-up occurred more frequently in t(8;21) patients carrying c-KIT mutations than in those without the mutation, although the difference was significant only in a specific patient subgroup with no WT1 mutations (P=0.014). CONCLUSIONS: The incidences of mutations in epigenetic genes are very low in CBF AML; however, c-KIT and WT1 mutations occur more frequently than others. The poor prognostic impact of c-KIT mutation in t(8;21) AML patients only applies in a specific patient subgroup without WT1 mutations. The prognostic impact of WT1 mutation in CBF AML is not evident and further investigation is required.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Asian Continental Ancestry Group/*genetics ; CCAAT-Enhancer-Binding Proteins/*genetics ; Child ; Core Binding Factors/genetics ; Disease-Free Survival ; Epigenesis, Genetic ; Female ; Humans ; Incidence ; Leukemia, Myeloid, Acute/*diagnosis/epidemiology/genetics ; Male ; Middle Aged ; Mutation ; Prognosis ; Proto-Oncogene Proteins c-cbl/*genetics ; Proto-Oncogene Proteins c-kit/*genetics ; Republic of Korea/epidemiology ; Survival Rate ; Translocation, Genetic ; WT1 Proteins/*genetics ; Young Adult

BACKGROUND: Few clinical studies have clarified the prognostic factors that affect clinical outcomes for patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) after immunochemotherapy. METHODS: A total of 158 patients with relapsed or refractory DLBCL were enrolled. All patients underwent positron emission tomography/computed tomography (PET/CT) before and after salvage therapy. All enrolled patients previously received the ifosfamide, carboplatin, and etoposide regimen. Clinical outcomes were compared according to several factors (age > or = 65 years, low age-adjusted International Prognostic Index [aa-IPI], maximum standardized uptake value [SUVmax] <6.0 on PET/CT, time to relapse > or =12 months, complete response after salvage therapy). A low aa-IPI, SUVmax <6.0, and time to relapse > or = 12 months were independent prognostic factors for survival. RESULTS: In univariate analysis and multivariate analysis, SUVmax below 6.0 (P<0.001 for progression-free survival (PFS), P<0.001 for overall survival (OS)) and low aa-IPI (P<0.001 for PFS, P<0.001 for OS) were independent prognostic factors associated with favorable outcome. CONCLUSION: The aa-IPI and initial SUVmax were powerful prognostic factors in patients with relapsed or refractory DLBCL.
Carboplatin ; Disease-Free Survival ; Electrons* ; Etoposide ; Humans ; Ifosfamide ; Lymphoma, B-Cell* ; Multivariate Analysis ; Positron-Emission Tomography ; Positron-Emission Tomography and Computed Tomography ; Recurrence ; Salvage Therapy

Using the Korean public health insurance database, we analyzed patients diagnosed as benign prostatic hyperplasia (BPH) from 2004 to 2008. Age and year-specific amount and seasonal variation of hospital visits (HV), duration of treatment (DT), the total and per capita amount of insurance payment (TAIP, PCIP) were evaluated. A total of 12,088,995 HV were studied. Total HV increased 1.7 times and DT almost doubled in 2008 compared to those in 2004. HV, DT, and TAIP showed linearly increasing patterns year by year. In a time series analysis, HV increased in winter and demonstrated seasonality in a 12-month cycle. In a Poisson regression analysis, the annual variations of HV, DT, TAIP, and PCIP were different by age groups. In patients older than 40 yr, HV significantly increased 1.10-1.16 times compared to that of the previous year. DT markedly increased in their 60s and 80s patients. The rate of increase in PCIP was steeper in patients 50 yr and older than in the others.Health care utilization due to BPH was rapidly increasing in Korea and it was remarkable in the elderly population. Seasonal variation of HV demonstrated that health care utilization increased in winter.
Adult ; Aged ; Aged, 80 and over ; Cost of Illness ; Health Care Costs ; Humans ; Insurance, Health/*economics/statistics & numerical data ; Male ; Middle Aged ; Patient Acceptance of Health Care/*statistics & numerical data ; Prostatic Hyperplasia/*economics/*epidemiology/therapy ; Republic of Korea/epidemiology ; Retrospective Studies ; Seasons ; Young Adult

Using the Korean public health insurance database, we analyzed patients diagnosed as benign prostatic hyperplasia (BPH) from 2004 to 2008. Age and year-specific amount and seasonal variation of hospital visits (HV), duration of treatment (DT), the total and per capita amount of insurance payment (TAIP, PCIP) were evaluated. A total of 12,088,995 HV were studied. Total HV increased 1.7 times and DT almost doubled in 2008 compared to those in 2004. HV, DT, and TAIP showed linearly increasing patterns year by year. In a time series analysis, HV increased in winter and demonstrated seasonality in a 12-month cycle. In a Poisson regression analysis, the annual variations of HV, DT, TAIP, and PCIP were different by age groups. In patients older than 40 yr, HV significantly increased 1.10-1.16 times compared to that of the previous year. DT markedly increased in their 60s and 80s patients. The rate of increase in PCIP was steeper in patients 50 yr and older than in the others.Health care utilization due to BPH was rapidly increasing in Korea and it was remarkable in the elderly population. Seasonal variation of HV demonstrated that health care utilization increased in winter.
Adult ; Aged ; Aged, 80 and over ; Cost of Illness ; Health Care Costs ; Humans ; Insurance, Health/*economics/statistics & numerical data ; Male ; Middle Aged ; Patient Acceptance of Health Care/*statistics & numerical data ; Prostatic Hyperplasia/*economics/*epidemiology/therapy ; Republic of Korea/epidemiology ; Retrospective Studies ; Seasons ; Young Adult