Seonyang Park

Marchiafava-Bignami disease: serial changes in corpus callosum on MRI.

SummarySerial MRI findings of changes in corpus callosum lesions in two cases of Marchiafava-Bignami disease are presented. In both, MRI displayed diffuse swelling of the corpus callosum in the acute stage, thought to represent oedema and demyelination. In the chronic stage, in addition to atrophy of the corpus callosum with presumed focal necrosis, previously undescribed focal hypointensity on T2-weighted images, of unknown cause, was observed in the corpus callosum.

Diffusion-weighted MRI in cystic or necrotic intracranial lesions.

Abstract Our purpose was to investigate the signal intensities of cystic or necrotic intracranial lesions on diffusion-weighted MRI (DWI) and measure their apparent diffusion coefficients (ADC). We examined 39 cystic or necrotic intracranial lesions in 33 consecutive patients: five malignant gliomas, seven metastases, two other necrotic tumours, a haemangioblastoma, three epidermoids, an arachnoid cyst, seven pyogenic abscesses, 12 cases of cysticercosis and one of radiation necrosis. DWI was performed on a 1.5 T unit using a single-shot echo-planar spin-echo pulse sequence with b 1000 s/mm2. The signal intensity of the cystic or necrotic portion on DWI was classified by visual assessment as markedly low (as low as cerebrospinal fluid), slightly lower than, isointense with, and slightly or markedly higher than normal brain parenchyma. ADC were calculated in 31 lesions using a linear estimation method with measurements from b of 0 and 1000 s/mm2. The cystic or necrotic portions of all neoplasms (other than two metastases) gave slightly or markedly low signal, with ADC of more than 2.60 × 10−3 mm2/s. Two metastases in two patients showed marked high signal, with ADC of 0.50 × 10−3 mm2/s and 1.23 × 10−3 mm2/s, respectively. Epidermoids showed slight or marked high signal, with ADC of less than 1.03 × 10−3 mm2/s. The arachnoid cyst gave markedly low signal, with ADC of 3.00 × 10−3 mm2/s. All abscesses showed marked high signal, with ADC below 0.95 × 10−3 mm2/s. The cases of cysticercosis showed variable signal intensity; markedly low in five, slightly low in three and markedly high in four.

Human AQP5 plays a role in the progression of chronic myelogenous leukemia (CML).

Aquaporins (AQPs) have previously been associated with increased expression in solid tumors. However, its expression in hematologic malignancies including CML has not been described yet. Here, we report the expression of AQP5 in CML cells by RT-PCR and immunohistochemistry. While normal bone marrow biopsy samples (n = 5) showed no expression of AQP5, 32% of CML patient samples (n = 41) demonstrated AQP5 expression. In addition, AQP5 expression level increased with the emergence of imatinib mesylate resistance in paired samples (p = 0.047). We have found that the overexpression of AQP5 in K562 cells resulted in increased cell proliferation. In addition, small interfering RNA (siRNA) targeting AQP5 reduced the cell proliferation rate in both K562 and LAMA84 CML cells. Moreover, by immunoblotting and flow cytometry, we show that phosphorylation of BCR-ABL1 is increased in AQP5-overexpressing CML cells and decreased in AQP5 siRNA-treated CML cells. Interestingly, caspase9 activity increased in AQP5 siRNA-treated cells. Finally, FISH showed no evidence of AQP5 gene amplification in CML from bone marrow. In summary, we report for the first time that AQP5 is overexpressed in CML cells and plays a role in promoting cell proliferation and inhibiting apoptosis. Furthermore, our findings may provide the basis for a novel CML therapy targeting AQP5.

Doxorubicin-Based Chemotherapy for Diffuse Large B-Cell Lymphoma in Elderly Patients Comparison of Treatment Outcomes between Young and Elderly Patients and the Significance of Doxorubicin Dosage

Although many studies of elderly patients with non‐Hodgkin lymphoma have focused on the dose intensity of chemotherapy, few studies have restricted the histologic inclusion criteria such that only patients with diffuse large B‐cell lymphoma (DLCL) are considered. In the current study, treatment outcomes for elderly patients (age ≥ 60 years) were analyzed, with emphasis on the dose intensity of doxorubicin.

Nilotinib combined with multiagent chemotherapy for newly diagnosed Philadelphia-positive acute lymphoblastic leukemia

We investigated the effects of nilotinib plus multiagent chemotherapy, followed by consolidation/maintenance or allogeneic hematopoietic cell transplantation (allo-HCT) for adult patients with newly diagnosed Philadelphia-positive (Ph-pos) acute lymphoblastic leukemia (ALL). Study subjects received induction treatment that comprised concurrent vincristine, daunorubicin, prednisolone, and nilotinib. After achieving complete hematologic remission (HCR), subjects received either 5 courses of consolidation, followed by 2-year maintenance with nilotinib, or allo-HCT. Minimal residual disease (MRD) was assessed at HCR, and every 3 months thereafter. The molecular responses (MRs) were defined as MR3 for BCR-ABL1/G6PDH ratios ≤10(-3) and MR5 for ratios <10(-5). Ninety evaluable subjects, ages 17 to 71 years, were enrolled in 17 centers. The HCR rate was 91%; 57 subjects received allo-HCT. The cumulative MR5 rate was 94%; the 2-year hematologic relapse-free survival (HRFS) rate was 72% for 82 subjects that achieved HCR, and the 2-year overall survival rate was 72%. Subjects that failed to achieve MR3 or MR5 were 9.1 times (P = .004) or 6.3 times (P = .001) more prone to hematologic relapse, respectively, than those that achieved MR3 or MR5. MRD statuses just before allo-HCT and at 3 months after allo-HCT were predictive of 2-year HRFS. Adverse events occurred mainly during induction, and most were reversible with dose reduction or transient interruption of nilotinib. The combination of nilotinib with high-dose cytotoxic drugs was feasible, and it effectively achieved high cumulative complete molecular remission and HRFS rates. The MRD status at early postremission time was predictive of the HRFS. This trial was registered at www.clinicaltrials.gov as #NCT00844298.

Comparative analysis between azacitidine and decitabine for the treatment of myelodysplastic syndromes

The present study aimed to directly compare the efficacy and safety of azacitidine and decitabine in patients with myelodysplastic syndromes (MDS). We compared the overall response rate (ORR) (complete responses, partial responses, marrow complete responses, and haematological improvements), overall survival (OS), event‐free survival (EFS), time to leukaemic transformation, and adverse outcomes between azacitidine and decitabine. To minimize the effects of treatment selection bias in this observational study, adjustments were made using the propensity‐score matching method. Among 300 patients, 203 were treated with azacitidine and 97 with decitabine. Propensity‐score matching yielded 97 patient pairs. In the propensity‐matched cohort, there were no significant differences between the azacitidine and decitabine groups regarding ORR (44% vs. 52%), OS (26 vs. 22·9 months), EFS (7·7 vs. 7·0 months), and rate of leukaemic transformation (16% vs. 22% at 1 year). In patients ≥65 years of age, survival was significantly better in the azacitidine group (P = 0·017). Patients who received decitabine experienced more frequent episodes of grade 3 or 4 cytopenia and infectious episodes. We found that azacitidine and decitabine showed comparable efficacy. Among patients ≥65 years of age, survival was significantly better in the azacitidine group (ClinicalTrials.gov Identifier: NCT01409070).

First-line ifosfamide, methotrexate, etoposide and prednisolone chemotherapy +/- radiotherapy is active in stage I/II extranodal NK/T-cell lymphoma.

Although most patients diagnosed with extranodal NK/T-cell lymphoma (NTCL) have localized disease, radiotherapy alone is unsatisfactory because of frequent systemic failure and conventional doxorubicin-based chemotherapy has low efficacy. Twenty-six patients with NTCL received ifosfamide, methotrexate, etoposide and prednisolone (IMEP) chemotherapy as first-line treatment [ifosfamide 1.5 g/m2 (days 1 – 3), methotrexate 30 mg/m2 (days 3 and 10), etoposide 100 mg/m2 (days 1 – 3) and prednisolone 120 mg (days 1 – 5)]. Radiotherapy was administered only to patients with Ann Arbor stage I/II that had not achieved complete remission (CR) or to those that developed local failure after completing chemotherapy. Sixteen patients (group A) had nasal or upper aerodigestive tract localization (stage I/II) and 10 (group B) had extranasal or disseminated disease. Of the 14 evaluable patients in group A, 11 (79%) achieved CR after IMEP alone and 13 (93%) after chemotherapy ± additional radiotherapy. Although, out of the 11 patients who achieved CR with chemotherapy alone, seven developed recurrence, all recurrences were local failure and successfully treated by additional curative radiotherapy. However, patients in group B responded poorly (CR 13%). IMEP regimen was active in NTCL patients with nasal or upper aerodigestive tract localization. Considering local failure rate after IMEP alone, initial IMEP chemotherapy followed by radiotherapy may be a promising treatment strategy in this subset of NTCL.

A multicenter retrospective analysis of adverse events in Korean patients using bortezomib for multiple myeloma

The proteasome inhibitor bortezomib has demonstrated clinical activity in patients with multiple myeloma (MM). Adverse events, including thrombocytopenia and peripheral neuropathy, have affected 30% to 60% of patients overall, and interrupted therapy in 10% to 20%. No prior toxicity data are available for Asian patients who have used bortezomib for MM. We used National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0, to review the clinical records of patients with an MM diagnosis from 25 centers in Korea. The included patients were treated with bortezomib alone or in combination with other agents, including thalidomide. Ninety-five MM patients were treated. The patients had a median age of 60 years (range, 42-77 years). The median number of previous treatments was 3 (range, 0–10), and 39% of the patients had been treated with 4 or more major classes of agents, including thalidomide (67%), and autologous stem cell transplantation (51%). Regimens included bortezomib only in 38 patients (40%), bortezomib plus dexamethasone in 34 patients (36%), and bortezomib plus a thalidomide-containing regimen in 23 patients (24%). The analysis of patient response to therapy revealed a complete response (CR) or a near-CR in 31 patients (33%) and a partial response in 30 patients (32%), for an objective response rate of 65% in 93 patients. The most common adverse events reported were thrombocytopenia (47%), sensory neuropathy (42%), anemia (31%), and leukopenia (31%). Thirteen patients (14%) stopped therapy because of adverse events (neuropathy, 8; infection, 4; diarrhea, 1). Neuropathy greater than grade 2 was more frequent in patients who received 4 or more prior therapy regimens (17/37) than in those who received 3 or fewer (14/58). In addition, therapy including thalidomide was significantly correlated with neuropathy of grades 1 to 3 (P = .001). We identified 6 therapy-related deaths (6%) within 20 days after the last dose of borte-zomib. The causes of death were infection in 3 patients, disease progression in 2 patients, and suicide in 1 patient. The incidences of thrombocytopenia and neurotoxicity were similar; however, gastrointestinal toxicities were relatively low in Korean patients compared with those reported in Western studies. Significant neuropathy was associated with the number of prior regimens and combination with thalidomide. These findings provide useful information for clinicians and patients using bortezomib.

Microcystic meningiomas: radiological characteristics of 16 cases

SummaryBackground. As a rare subtype of meningioma, only a few reports deal with radiological characteristics of microcystic meningiomas and the problem remains controversial. The authors have analyzed the radiological findings of a series of microcystic meningiomas with a special focus on magnetic resonance images (MRI) and conventional angiography.Method. Sixteen patients of histologically proven microcystic meningiomas were included. Analysis of preoperative MRI including signal intensity characteristics, enhancement patterns and peritumoural edema were performed and correlated with angiographic and histological findings. Peritumoural edema was graded using edema index (EI) which was defined as the ratio of VE/VT.Findings. The tumours were uniformly visualized as a high-signal mass lesion in T2-weighted images and as a low-signal mass lesion in T1-weighted images regardless of tumour vascularity shown by angiography. T2-weighted images revealed that peritumoural brain edema was severe in 11, moderate in 1, mild in 2 and negligible in 2 patients and this was closely related to the co-existence of irregular tumour marginal enhancement. However, other features failed to distinguish these lesions from other subtypes of meningioma.Conclusions. The cases presented demonstrate that characteristic MRI findings suggestive of microcystic meningiomas are; (1) low signal intensity mass in T1- and high signal intensity mass in T2-weighted images; (2) high incidence of peritumoural edema.

Correlation between plasma activity of ADAMTS-13 and coagulopathy, and prognosis in disseminated intravascular coagulation

INTRODUCTION In disseminated intravascular coagulation (DIC), widespread activation of intravascular coagulation accompanied with florid endothelial activation results in release of unusually large von Willebrand factor (ULvWF) from endothelium. Circulating a disintegrin-like and metalloprotease with thrombospondin type 1 repeats (ADAMTS)-13 may be consumed through the ongoing cleavage of ULvWF, resulting in a secondary deficiency of ADAMTS-13 in DIC. We determined whether ADAMTS-13 activity showed a significant correlation with the activation status of the coagulation system and hospital mortality in DIC. MATERIALS AND METHODS ADAMTS-13 activity was assayed by fluorescence resonance energy transfer assay in 97 patients who were clinically suspected to have DIC. RESULTS ADAMTS-13 activity gradually decreased based on the DIC score and D-dimer levels and was correlated with the antithrombin level, representing the consumption of ADAMTS-13 during the ongoing coagulation process. There were no correlation between ADAMTS-13 activity and neutrophil CD64 expression as a neutrophil activation marker and circulating IL-6 level as an inflammatory marker. Patients with a low activity of ADAMTS-13 (< or = 56.4%) had a poor survival rate compared to patients with a high activity of ADAMTS-13. CONCLUSIONS We conclude that ADAMTS-13 activity is strongly correlated with the severity of coagulopathy and hospital mortality. ADAMTS-13 may serve as a diagnostic and prognostic marker of DIC.