We report a long-term follow-up of unstable hemoglobin (Hb) patient. He was diagnosed as Hb Madrid [beta115(G17)Ala-->Pro] by direct DNA sequencing and restriction enzyme analysis. Hydroxyurea had been given for beta-chain hemoglobinopathies through activation of gamma(gamma)-chain synthesis. Nowadays he still needs transfusion three or four times per year, but he had been free of hemolytic crisis after hydroxyurea. Although he has been treated for hemochromatosis with parenteral and oral iron-chelating agents, liver cirrhosis complicated by esophageal varix was developed and treated with endoscopic ligation. In addition, he is on warfarin maintenance for anticoagulation therapy for extensive portal vein and superior mesenteric vein thrombosis which presented with abdominal pain and diagnosed by CT scan. In management of unstable Hb patients, physician should monitor and control the serum ferritin level with iron-chelating agents, and be aware of possible long-term complication including hemochromatosis, cirrhosis or thromboembolism.
Abdominal Pain ; Esophageal and Gastric Varices ; Ferritins ; Fibrosis ; Follow-Up Studies ; Hemochromatosis ; Hemoglobinopathies ; Hemoglobins ; Hemoglobins, Abnormal ; Humans ; Hydroxyurea ; Ligation ; Liver Cirrhosis ; Mesenteric Veins ; Organothiophosphorus Compounds ; Portal Vein ; Restriction Mapping ; Sequence Analysis, DNA ; Thromboembolism ; Thrombosis ; Warfarin

The homeostasis of microenvironment in central nervous system, essential for normal function, is maintained by blood-brain barrier (BBB). ZO-1 in tight junctions (TJs) plays an important role in maintaining BBB endothelial ion and solute barriers. Malfunction of BBB by reactive oxygen species has been attributed to disruption of TJs. This study examined H2 O2 effects on paracellular permeability and changes in TJ protein ZO-1 using primary culture of bovine brain microvessel endothelial cells. The BBB permeability,measured as TER, increased in a dose-and time-dependent manner when treated with H2O2 (0.01, 0.1, 1.0 mM). Cytotoxicity test revealed that H2O2 did not cause cell death below 1 mM H2 O2 within 4 hr. H2O2 caused intermittent disruption and loss of ZO-1 at tight junctions, but ZO-1 maintained steady state levels of expression. In conclusion, we report that H2O2 induces increased paracellular permeability of BBB that is accompanied with alterations in localization of ZO-1.
Blood-Brain Barrier ; Brain ; Cell Death ; Central Nervous System ; Endothelial Cells ; Homeostasis ; Microvessels ; Oxidative Stress* ; Permeability ; Reactive Oxygen Species ; Tight Junctions*

Background: The aim of the present study was to evaluate the prognostic significance of B-cell lymphocyte kinase (BLK) expression for survival outcomes in diffuse large B-cell lymphoma (DLBCL) patients treated with R-CHOP. Methods: We retrospectively analyzed the medical records of 89 patients from two tertiary referral hospitals. The expression of BLK, SYK, and CDK1 were evaluated in a semiquantitative method using an H-score, and the proportions of BCL2 and C-MYC were evaluated. Results: A total of 89 patients received R-CHOP chemotherapy as a first-line chemotherapy. The expression rates of BLK in tumor cells was 39.2% (n = 34). BLK expression status was not significantly associated with clinical variables; however, BLK expression in tumor cells was significantly associated with the expression of both C-MYC and BCL2 (p = .003). With a median follow-up of 60.4 months, patients with BLK expression had significantly lower 5-year progression-free survival (PFS) and overall survival rates (49.8% and 60.9%, respectively) than patients without BLK expression (77.3% and 86.7%, respectively). In multivariate analysis for PFS, BLK positivity was an independent poor prognostic factor (hazard ratio, 2.208; p = .040). Conclusions Here, we describe the clinicopathological features and survival outcome according to expression of BLK in DLBCL. Approximately 39% of DLBCL patients showed BLK positivity, which was associated as a predictive marker for poor prognosis in patients who received R-CHOP chemotherapy.

PURPOSE: This study was conducted to explore the process and operation of a cancer multidisciplinary team (MDT) after the reimbursement decision in Korea, and to identify ways to overcome the major barriers to effective and sustainable MDTs. MATERIALS AND METHODS: Approximately 1,000 cancer specialists, including medical oncologists, surgical oncologists, radiation oncologists, pathologists, and radiologists in general hospitals in Koreawere invited to complete the survey. The questionnaire covered the following topics: organizational structure of MDTs, candidates for consulting, the clinical decision-making initiative, and responsibility for dealing with legal disputes. RESULTS: We collected a total of 179 responses (18%) from physicians at institutions where an MDT approach was active. A surgical oncologist (91%), internist (90%),radiologist (89%),radiation oncologist (86%), pathologist (71%), and trainees (20%) regularly participated in MDT operations. Approximately 55% of respondents stated that MDTs met regularly. In cases of a split opinion, the physician in charge (69%) or chairperson (17%) made the final decision, and most (86%) stated they followed the final decision. About 15% and 32% of respondents were “very satisfied” and “satisfied,” respectively, with the current MDT's operations. Among 38 institutional representatives, 34% responded that the MDT operation became more active and 18% stated an MDT was newly implemented after the reimbursement decision. CONCLUSION: The reimbursement decision invigorated MDT operations in almost half of eligible hospitals. Dissatisfaction regarding current MDTs was over 50%, and the high discordance rates regarding risk sharing suggest that it is necessary to revise the current system of MDTs.
Clinical Decision-Making ; Dissent and Disputes ; Hospitals, General ; Korea* ; Specialization ; Surveys and Questionnaires

Many predictive models have been proposed for better stratification of diffuse large B-cell lymphoma (DLBCL). Hans' algorithm has been widely used as standard to sub-classify DLBCL into germinal center B-cell (GCB) and non-GCB origins. However, there have been disagreements in the literature regarding its prognostic significance. Here, we retrospectively analyzed Hans' algorithm and the individual immunohistochemical biomarkers at different cut-off values (5%, 30%, 50% or 75%) in 94 Korean patients with DLBCL treated with combination chemotherapy with cyclophosphamide, daunorubicin, vincristine, and prednisone. No significant differences were observed between the GCB (18 patients, 19.1%) and non-GCB (76, 80.9%) groups. Among individual biomarkers, CD10 negativity (cut point: 30%) and bcl-6 positivity (cut point: 5%) were independent good prognostic markers in progression-free survival (PFS), whereas bcl-6 (cut point: 5%) positivity was an independent good prognostic marker in overall survival irrelevant of international prognostic index. The present study showed the lack of predictability of Hans' algorithm in DLBCL patients, and that CD10, Bcl-6 may have diverse prognostic significance at different cut-off values. Our results suggest that the proposed cut-off value may not be applied universally, and that the optimal cut-off value may need to be optimized for individual laboratory.
Adult ; Aged ; Aged, 80 and over ; Algorithms ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Cyclophosphamide/therapeutic use ; DNA-Binding Proteins/analysis ; Doxorubicin/therapeutic use ; Female ; Humans ; Lymphoma, Large B-Cell, Diffuse/classification/*drug therapy ; Male ; Middle Aged ; Neprilysin/analysis ; Prednisone/therapeutic use ; Prognosis ; Republic of Korea ; Retrospective Studies ; Tumor Markers, Biological/*analysis ; Vincristine/therapeutic use

We investigated the effectiveness of lamivudine to prevent hepatitis flare up due to reactivation of hepatitis-B virus (HBV) in hepatitis-B surface antigen (HBsAg)-positive patients with Non-Hodgkin's lymphoma (NHL) during cytotoxic chemotherapy. HBsAg-positive patients with NHL were identified from the lymphoma database of the Asan Medical Center from January 1995 to August 2002, and their medical records were reviewed. We found that 31 patients were received cytotoxic chemotherapy among 41 NHL patients with HBsAg-positive during same period. We divided them into 2 groups of HBsAg patients with NHL as follows: Group A who received cytotoxic chemotherapy with lamivudine 100 mg daily; Group B without any prophylactic antiviral therapy. There were no significant differences between Group A and B in several clinical variables. Seventeen patients (85%) in group B and one patient (9%) in Group A had hepatitis due to reactivation of HBV (p<0.001), with one hepatic failure related death in Group B and none in group A. The mean dose intensity of adriamycin actually delivered was 13.3 mg/m2/week (80% Relative Dose intensity (RDI)) in Group A and 9.1 mg/m2/week (55% RDI) in Groups B (p<0.001). Our data suggest that the frequency of chemotherapy-related HBV reactivation may be significantly decreased by lamivudine prophylaxis with maintenance of the dosage of adriamycin.
Adult ; Aged ; Antibiotics, Antineoplastic/*therapeutic use ; Doxorubicin/*therapeutic use ; Female ; Hepatitis B/complications/diagnosis/*drug therapy ; Hepatitis B Surface Antigens/*analysis ; Hepatitis B Virus/metabolism ; Human ; Lamivudine/*therapeutic use ; Lymphoma, Non-Hodgkin/complications/*drug therapy/metabolism ; Male ; Middle Aged ; Reverse Transcriptase Inhibitors/*therapeutic use ; Survival Rate ; Virus Activation