Background/Aims: We evaluated the feasibility and long-term efficacy of the combination of cytarabine, idarubicin, and all-trans retinoic acid (ATRA) for treating patients with newly diagnosed acute promyelocytic leukemia (APL). Methods: We included 87 patients with newly diagnosed acute myeloid leukemia and a t(15;17) or promyelocytic leukemia/retinoic acid receptor alpha (PML-RARα) mutation. Patients received 12 mg/m2/day idarubicin intravenously for 3 days and 100 mg/m2/day cytarabine for 7 days, plus 45 mg/m2/day ATRA. Clinical outcomes included complete remission (CR), relapse-free survival (RFS), overall survival (OS), and the secondary malignancy incidence during a 20-year follow-up. Results: The CR, 10-year RFS, and 10-year OS rates were 89.7%, 94.1%, and 73.8%, respectively, for all patients. The 10-year OS rate was 100% for patients that achieved CR. Subjects were classified according to the white blood cell (WBC) count in peripheral blood at diagnosis (low-risk, WBC < 10,000/mm3; high-risk, WBC ≥ 10,000/mm3). The low-risk group had significantly higher RFS and OS rates than the high-risk group, but the outcomes were not superior to the current standard treatment (arsenic trioxide plus ATRA). Toxicities were similar to those observed with anthracycline plus ATRA, and higher than those observed with arsenic trioxide plus ATRA. The secondary malignancy incidence after APL treatment was 2.7%, among the 75 patients that achieved CR, and 5.0% among the 40 patients that survived more than 5 years after the APL diagnosis. Conclusions Adding cytarabine to anthracycline plus ATRA was not inferior to anthracycline plus ATRA alone, but it was not comparable to arsenic trioxide plus ATRA. The probability of secondary malignancy was low.

Pancreatic endocrine tumors are low-to-intermediate-grade neoplasms arising from the pancreatic islets that produce various hormones. These tumors account for a minority of pancreatic tumors and are generally considered functional if they are associated with a hormonal syndrome. Adrenocorticotropic hormone-secreting tumors (ACTHomas) are very rare and require special clinical consideration. Patients with ACTH-secreting tumors usually present with Cushing's syndrome, due to ectopic ACTH production. ACTHomas have a poor prognosis because of early metastasis and difficulty controlling corticosteroid production. We report a 62-year-old male with an ACTH-secreting metastatic pancreatic neuroendocrine tumor, who did not respond to somatostatin analogs and died.
Adrenocorticotropic Hormone ; Cushing Syndrome ; Humans ; Islets of Langerhans ; Male ; Middle Aged ; Neoplasm Metastasis ; Neuroendocrine Tumors ; Pancreas ; Prognosis ; Somatostatin

Neuromuscular complications after hematopoietic stem cell transplantation are rarely reported. We report one male patient with ophthalmoplegia, flaccid paralysis, and hyporeflexia after peripheral blood stem cell transplantation (PBSCT). A cerebrospinal fluid study showed albuminocytologic dissociation, and nerve conduction studies revealed demyelinating polyneuropathies. Intravenous immunoglobulin was tried following a diagnosis of Guillain-Barre syndrome (GBS). After 11 months he was able to walk alone with a walker. This is probably the first report of GBS related to PBSCT in Korea.
Dissociative Disorders ; Guillain-Barre Syndrome ; Hematopoietic Stem Cell Transplantation ; Humans ; Immunoglobulins ; Korea ; Male ; Neural Conduction ; Ophthalmoplegia ; Paralysis ; Peripheral Blood Stem Cell Transplantation ; Polyneuropathies ; Reflex, Abnormal ; Walkers

BACKGROUND: Fluorescence in situ hybridization (FISH) analysis can provide important information in the management of patients with hematologic malignancies. However, FISH performed in addition to G-banded karyotype can be labor-intensive and expensive. The aim of this study was to evaluate whether FISH gives additional information in the setting of adequate conventional cytogenetics in cases of hematologic malignancies. METHODS: Bone marrow aspirates were obtained from 135 patients at diagnosis (56 AML, 32 MDS, 20 ALL, and 27 MM) between 2005 and 2010. Interphase FISH was performed using the following probes: BCR/ABL1, AML1/ETO, PML/RARA, CBFB, MLL, EGR1, CEP8, and D7S486 for AML; CEP8, D20S108, EGR1, and D7S486 for MDS; BCR/ABL1, MLL, CDKN2A (p16), ETV6, and 6q21/c-myc for ALL; IgH, TP53, D13S25, IgH/CCND1, IgH/MAF, IgH/FGFR3, and 1q21/8p21 for MM. We compared the results of FISH with the corresponding aberrations identified by G-banded karyotype. RESULTS: Additional genetic aberrations detected by FISH (which were not identified by G-banded karyotype) were 4%, 9%, 50%, and 67% in AML, MDS, ALL, and MM, respectively. In ALL, CDKN2A and ETV6 FISH revealed additional genetic aberrations in 33% and 28% of cases, respectively. In MM, FISH was of benefit in detecting IgH, D13S25, TP53, and 1q21 rearrangements, not detected by G-banded karyotype (31%, 36%, 20%, and 40%, respectively). CONCLUSION: These results suggest that performing FISH in addition to G-banded karyotype may contribute little additional genetic information in AML and MDS, whereas routine FISH analysis appears to be an efficient screening method in ALL and MM.
Bone Marrow ; Cytogenetics ; Fluorescence ; Hematologic Neoplasms ; Humans ; In Situ Hybridization ; Interphase ; Karyotype ; Leukemia, Myeloid, Acute ; Mass Screening ; Multiple Myeloma ; Myelodysplastic Syndromes ; Precursor Cell Lymphoblastic Leukemia-Lymphoma

The pyrimidine antimetabolite 5-fluorouracil (5-FU) is a chemotherapeutic agent used widely for various tumors. Common side effects of 5-FU are related to its effects on the bone marrow and gastrointestinal epithelium. Neurotoxicity caused by 5-FU is uncommon, although acute and delayed forms have been reported. Wernicke's encephalopathy is an acute, neuropsychiatric syndrome resulting from thiamine deficiency, and has significant morbidity and mortality. Central nervous system neurotoxicity such as Wernicke's encephalopathy following chemotherapy with 5-FU has been reported rarely, although it has been suggested that 5-FU can produce adverse neurological effects by causing thiamine deficiency. We report a patient with Wernicke's encephalopathy, reversible with thiamine therapy, associated with 5-FU-based chemotherapy.
Acute Disease ; Antimetabolites, Antineoplastic/*adverse effects ; Female ; Fluorouracil/*adverse effects ; Humans ; Magnetic Resonance Imaging ; Middle Aged ; Nasopharyngeal Neoplasms/drug therapy/radiotherapy ; Thiamine/therapeutic use ; Thiamine Deficiency/*complications/diagnosis ; Wernicke Encephalopathy/*chemically induced/diagnosis

BACKGROUND: Most of adult patients with chronic immune thrombocytopenic purpura (ITP) that was refractory or relapsed to high-dose corticosteroid have been treated with splenectomy as a 2nd line treatment. However, these patients may have increased morbidity and mortality according to the operation and the increased risk of infection for a lifetime after splenectomy. Despite of the above risks, 30~40% of these patients can't maintain remission. Furthermore, the remission rate after splenectomy is relatively lower in patients with corticosteroid-refractory chronic ITP than that in those patients with corticosteroid-responsiveness. We studied whether danazol, an attenuated androgen, is useful or safe as 2nd line treatment for chronic ITP instead of splenectomy and which factors are associated with the response to danazol. METHODS: Among the patients with chronic ITP who failed corticosteroid therapy in our hospital, 28 patients who received danazol as the 2nd line treatment were analyzed retrospectively. A complete response was defined that the platelet count was increased to 150 x 10(3)/microL, and a partial response was defined that the platelet count was increased above 50 x 10(3)/microL or there was an increased platelet count of more than 20 x 10(3)/microL from the pre-treatment platelet count when the platelet count was above 50 x 10(3)/microL at the time of danazol therapy. RESULTS: The median age of patients was 44 years (range: 19~67) and the number of male patients was 9 (32.1%) and the number of females was 19 (67.9%). The starting daily doses of danazol were variable from 200 to 600mg, though most of the patients were treated with 400mg daily (18 cases, 64.3%). The median duration of danazol therapy was 201.5 days (range: 13~973) and the median duration from ITP diagnosis to danazol treatment was 56 days (range: 20~2,430). Among the accrued 28 patients, 22 patients showed a response to danazol (78.5%); there were 6 patients (21.4%) with a complete response and 16 patients (57.1%) with a partial response. The median duration from danazol treatment to response was 30 days (range: 0~180). The median response duration of danazol treatment was 330 days (95% CI: 182~478) by the Kaplan-Meiyer method. For the danazol-responsive patients, 9 patients (40.9%) remained in remission and 13 patients (59.1%) relapsed. Grade 3~4 toxicity was observed in two patients and three patients stopped danazol because of adverse effects. Hepatotoxicity was the most common toxicity. CONCLUSION: Our findings suggest that danazol is a beneficial, safe choice as the 2nd line treatment for patients with chronic ITP that was refractory or relapsed to corticosteroid.
Adult ; Danazol* ; Diagnosis ; Female ; Humans ; Male ; Mortality ; Platelet Count ; Purpura, Thrombocytopenic, Idiopathic* ; Retrospective Studies ; Splenectomy

This is the first case report of a patient with a large serous cystadenoma accompanied by a juvenile granulosa cell tumor that was discovered in the remaining ovarian tissue. A 25-year-old female was presented with constipation and amenorrhea. Ultrasonography revealed a large cystic mass in the left ovary with a normal uterus. The remaining ovarian tissue seemed normal at first look after cystectomy, but showed abnormal consistency on palpation. The remaining ovarian tissue was removed and granulosa cell tumor was confirmed by pathologic examination. The patient has been followed up for 30 months without evidence of recurrence. We would like to emphasize the importance of inspection, and palpation of remaining ovarian tissue during operation to avoid risks of remaining ovarian pathology.
Adult ; Amenorrhea ; Constipation ; Cystadenoma, Serous* ; Cystectomy ; Female ; Granulosa Cell Tumor* ; Granulosa Cells* ; Humans ; Ovarian Neoplasms ; Ovary* ; Palpation ; Pathology ; Recurrence ; Ultrasonography ; Uterus

Leukotriene B4(LTB4), derived from arachidonic acid, is a potent chemotactic agent and activating factor for hematopoietic cells. In addition to host defense in vivo, several eicosanoids have been reported to be involved in stem cell differentiation or proliferation. In this study, we investigated the effect of LTB4 on human cord blood CD34+ hematopoietic stem cells (HSCs). LTB4 was shown to induce proliferation of HSC and exert anti-apoptotic effect on the stem cells. Blockade of interaction between LTB4 and its receptor enhanced self-renewal of the stem cells. Effect of LTB4 on differentiation of CD34+ HSCs were confirmed by clonogenic assays, and induction of the expression of BLT2 (the low- affinity LTB4 receptor), during the ex vivo expansion was confirmed by reverse transcription-PCR. Our results suggest that LTB4-BLT2 interaction is involved in the cytokine-induced differentiation and ex vivo expansion of hematopoietic stem cells.
Antigens, CD34/metabolism ; Apoptosis/drug effects ; Cell Differentiation/drug effects ; Cell Proliferation/drug effects ; Fetal Blood/cytology/drug effects ; Hematopoietic Stem Cells/*drug effects/metabolism ; Humans ; Leukotriene B4/*pharmacology ; Receptors, Leukotriene B4/genetics/metabolism ; Research Support, Non-U.S. Gov't ; Reverse Transcriptase Polymerase Chain Reaction ; *Signal Transduction

Female pelvic tuberculosis is almost invariably secondary to disease elsewhere, usually in the lungs. It is difficult to diagnose pelvic tuberculosis, because it is often a disease with absent or few non-specific symptoms. Pelvic tuberculosis should be considered in the differential diagnosis of all ovarian mass and pelvic malignancy. We report a case of retroperitoneal tuberculous lymphadenopathy that may be mistaken for pelvic malignancy, because of the nonspecific clinical features and radiologic findings. The diagnosis was made post-operatively by histopathology.
Diagnosis ; Diagnosis, Differential ; Female ; Humans ; Lung ; Lymphatic Diseases* ; Retroperitoneal Space ; Tuberculosis

PURPOSE: The HER2 gene encodes a 185-kd transmembrane glycoprotein receptor (p185(HER2)) that has partial homology with the epidermal growth factor receptor (EGFR) and shares intrinsic tyrosine kinase activity. The HER2 gene has been found to be amplified in various human cancers and to be associated with poor prognosis. The authors investigated the correlation between clinicopathologic factors and the overexpression of the p185(HER2) in Korean gastric adenocarcinoma patients, and determined whether the antiproliferative effects of anti- p185(HER2) antibody can also be observed on gastric cancer cell lines that overexpress this growth factor receptor. MATERIALS AND METHODS: We evaluated the relationship between p185(HER2) overexpression and clinicopathological features in 94 (M: F=52: 42) gastric adenocarcinoma patients (median age 59 years). Protein expression was analysed by immunohistochemical staining in paraffin embedded tissues with monoclonal antibody for p185(HER2). To explore the role of humanized anti-p185(HER2) monoclonal antibody trastuzumab (Herceptin ) in vitro, the growth curve of Korean gastric cancer cells that overexpress the p185(HER2) protein was studied and a cell cycle analysis was performed. RESULTS: p185(HER2) overexpression correlates positively with lymph node metastasis (p=0.002), distant metastasis (p=0.01), AJCC classification (p=0.01), higher relapse rate p=0.001), and a tendential association with the pT stage (p=0.054). p185(HER2) overexpression was found to be more frequent in advanced gastric cancer than early gastric cancer (54.1% vs 24.2%, p=0.008). Patients with overexpression of p185(HER2) were found to have significantly lower relapse-free (p=0.003) and overall survival (p= 0.0004) than patients without overexpression. Among several Korean gastric cancer cell lines, SNU-1, SNU-5, and SNU-620 overexpress p185(HER2). Trastuzumab inhibited the proliferation of p185(HER2) overexpressed Korean gastric cancer cell line by 21% with down-regulation of p185(HER2) protein expression. DNA fluorescence flow cytometry of propidium iodide-stained nuclei showed a reduction in the fraction of the S phase following treatment with trastuzumab. CONCLUSIONS: Taken together, our observations suggest the potential prognostic significance of p185(HER2) overexpression in Korean gastric adenocarcinoma patients and point to the need for further research on this mechanism. This suggests the possible use of p185(HER2) as a therapeutic target in gastric cancer.
Adenocarcinoma ; Cell Cycle ; Cell Line* ; Classification ; DNA ; Down-Regulation ; Flow Cytometry ; Fluorescence ; Genes, erbB-2 ; Glycoproteins ; Humans ; Lymph Nodes ; Neoplasm Metastasis ; Paraffin ; Prognosis ; Propidium ; Protein-Tyrosine Kinases ; Receptor, Epidermal Growth Factor ; Recurrence ; S Phase ; Stomach Neoplasms ; Trastuzumab