Jihyun Kwon

Comparison of therapeutic outcomes between surgical resection followed by R-CHOP and R-CHOP alone for localized primary intestinal diffuse large B-cell lymphoma.

Objectives:There is no confirmed treatment strategy for primary intestinal diffuse large B-cell lymphoma (DLBL). In this retrospective study, the purpose is to find an appropriate treatment strategy in patients with primary intestinal DLBL undergoing surgery followed by chemotherapy or chemotherapy alone. Methods:Seventy-six patients were newly diagnosed with DLBL and received treatment between March 2004 and June 2011. Forty-seven patients were treated with surgical resection followed by rituximab combined with cyclophosphamide, adriamycin, vincristine, and prednisolone (R-CHOP), and 29 patients were treated with R-CHOP chemotherapy alone. Results:The characteristics of the patients were as follows: the median age was 56.5 years (range, 15 to 85 y) with a female to male ratio of 1.00:1.45. There was no significant difference in patient characteristics between the 2 groups. The estimated 3-year progression-free survival rates (PFS) and overall survival rates (OS) of surgery followed by R-CHOP (surgery/R-CHOP) and R-CHOP alone (R-CHOP) groups were 92.2% and 74.8% (P=0.009) and 94.2% and 80.7% (P=0.049), respectively. In univariate analysis, significant differences were seen in estimated PFS and OS rates when comparing Lugano stages I and II1 with II2 and IIE (P=0.006 and 0.036), low and low-intermediate risk with high-intermediate risk (P=0.004 and 0.000), and surgery/R-CHOP group with R-CHOP group (P=0.009 and 0.049), respectively. In multivariate analysis, there were no independent predictive factors for survival. Conclusions:Patients treated with surgery followed by R-CHOP seemed to have a higher survival rate than those treated with R-CHOP alone. There were no significant prognostic factors for survival, but there were possible prognostic factors such as Lugano stage, International Prognostic Index risk, and treatment modality for PFS and OS.

Prospective Randomized Comparison of Idarubicin and High-Dose Daunorubicin in Induction Chemotherapy for Newly Diagnosed Acute Myeloid Leukemia

Purpose We compared two induction regimens, idarubicin (12 mg/m2/d for 3 days) versus high-dose daunorubicin (90 mg/m2/d for 3 days), in young adults with newly diagnosed acute myeloid leukemia (AML). Patients and Methods A total of 299 patients (149 randomly assigned to cytarabine plus idarubicin [AI] and 150 assigned to cytarabine plus high-dose daunorubicin [AD]) were analyzed. All patients received cytarabine (200 mg/m2/d for 7 days). Results Complete remission (CR) was induced in 232 patients (77.6%), with no difference in CR rates between the AI and AD arms (80.5% v 74.7%, respectively; P = .224). At a median follow-up time of 34.9 months, survival and relapse rates did not differ between the AI and AD arms (4-year overall survival, 51.1% v 54.7%, respectively; P = .756; cumulative incidence of relapse, 35.2% v 25.1%, respectively; P = .194; event-free survival, 45.5% v 50.8%, respectively; P = .772). Toxicity profiles were also similar in the two arms. Interestingly, overall and event-free survival times of patients with FLT3 internal tandem duplication (ITD) mutation were significantly different (AI v AD: median overall survival, 15.5 months v not reached, respectively; P = .030; event-free survival, 11.9 months v not reached, respectively; P = .028). Conclusion This phase III trial comparing idarubicin with high-dose daunorubicin did not find significant differences in CR rates, relapse, and survival. Significant interaction between the treatment arm and the FLT3-ITD mutation was found, and high-dose daunorubicin was more effective than idarubicin in patients with FLT3-ITD mutation.

Topical Recombinant Human Epidermal Growth Factor for Oral Mucositis Induced by Intensive Chemotherapy with Hematopoietic Stem Cell Transplantation: Final Analysis of a Randomized, Double-Blind, Placebo-Controlled, Phase 2 Trial

The aim of this study was to evaluate the efficacy and safety of recombinant human epidermal growth factor (rhEGF) oral spray for oral mucositis (OM) induced by intensive chemotherapy with hematopoietic stem cell transplantation. In this phase 2 study, patients were randomized to either rhEGF (50 microg/mL) or placebo in a 1:1 ratio. The primary endpoint was incidence of National Cancer Institute (NCI) grade ≥2 OM. A total of 138 patients were enrolled in this study. In the intention-to-treat analysis, rhEGF did not reduce the incidence of NCI grade ≥2 OM (p = 0.717) nor reduce its duration (p = 0.725). Secondary endpoints including the day of onset and duration of NCI grade ≥2 OM, the incidence of NCI grade ≥3 OM and its duration, and patient-reported quality of life were also similar between the two groups. In the per-protocol analysis, however, the duration of opioid analgesic use was shorter in the rhEGF group (p = 0.036), and recipients in the rhEGF group required a lower cumulative dose of opioid analgesics than those in the placebo group (p = 0.046), among patients with NCI grade ≥2 OM. Adverse events were mild and transient. This study found no evidence to suggest that rhEGF oral spray reduces the incidence of OM. However, further studies are needed to investigate the effect of rhEGF on OM-induced pain reduction after intensive chemotherapy.

Two Korean siblings with recently described ovarioleukodystrophy related toAARS2mutations

J.-M. Lee, H.-J. Yang, J.-H. Kwon, W.-J. Kim, S.-Y. Kim, E.-M. Lee, J.-Y. Park, Y. C. Weon, S. H. Park, B.-J. Gwon, J.-C. Ryu, S.-T. Lee, H.-J. Kim and B. Jeon Department of Neurology, Ulsan University Hospital, University of Ulsan College of Medicine, Department of Radiology, Ulsan University Hospital, University of Ulsan College of Medicine, Department of Nuclear Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, and Department of Neurology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea

Poor prognosis of hypocoagulability assessed by thrombin generation assay in disseminated intravascular coagulation.

Overall assessment of the hemostatic system including procoagulant and anticoagulant changes may help assess the clinical status and prognosis of disseminated intravascular coagulation (DIC). The thrombin generation assay provides useful information about the global hemostatic status. Therefore, we measured several parameters of global hemostatic potential by the thrombin generation assay in patients suspected of having DIC. A total of 114 patients with suspected DIC were included. The thrombin generation assay was performed on the calibrated automated thrombogram using tissue factor with or without the addition of thrombomodulin, showing three parameters: lag time, endogenous thrombin potential (ETP), and peak thrombin. Both 1 and 5 pmol/l tissue factor-stimulated ETP and peak thrombin were well correlated with DIC severity. Interestingly, antithrombin level greatly affected ETP, whereas protein C influenced lag time. Prognostic analysis revealed that the area under the curve of peak thrombin stimulated by 1 pmol/l tissue factor was superior to that of D-dimer. Moreover, multivariate Cox analysis showed that the lag time and time to peak with both 1 and 5 pmol/l tissue factor were independent prognostic markers. ETP and peak thrombin well reflect DIC severity. Hypocoagulability manifesting as prolonged lag time and time to peak is expected to be an independent prognostic marker in DIC.

Sequential spinal and intracranial dural metastases in gastric adenocarcinoma: A case report

Dural metastasis from primary gastric adenocarcinoma has been rarely reported, and its prognosis is very poor because it frequently leads to acute subdural hematoma. Here, we describe a case with sequential spinal and cranial dural metastases from gastric adenocarcinoma without subdural hematoma. A 43-year-old woman with gastric adenocarcinoma and well-controlled peritoneal carcinomatosis presented with back pain, right radiating leg pain, left facial palsy, and hearing loss. Magnetic resonance imaging of the spine and brain revealed dural masses at the lumbosacral junction with invasion to the L5 and S1 nerve roots and at the skull base with invasion to the internal auditory canal. She was treated with local radiotherapy, and her pain and neurologic symptoms improved after palliative radiotherapy. This is the first reported case of dural metastases of gastric adenocarcinoma of the spine and skull base but with a relatively indolent course and without subdural hematoma.

EGFR Mutation Status in Lung Adenocarcinoma-Associated Malignant Pleural Effusion and Efficacy of EGFR Tyrosine Kinase Inhibitors

Purpose Malignant pleural effusions (MPEs) are often observed in lung cancer, particularly adenocarcinoma. The aim of this study was to investigate epidermal growth factor receptor (EGFR) mutation status in lung adenocarcinoma-associated MPEs (LA-MPEs) and its correlation with efficacy of EGFR tyrosine kinase inhibitor (TKI) therapy. Materials and Methods Samples comprised 40 cell blocks of pathologically-confirmed LA-MPEs collected before the start of EGFR TKI therapy. EGFR mutation status was re-evaluated by peptide nucleic acid clamping and the clinical outcomes of EGFR TKI‒treated patients were analyzed retrospectively. Results EGFR mutations were detected in 72.5% of LA-MPE cell blocks (29/40). The median progression-free survival for patients with EGFR mutations in LA-MPEs was better than that for patients with wild-type EGFR (7.33 months vs. 2.07 months; hazard ratio, 0.486; 95% confidence interval, 0.206 to 1.144; p=0.032). The objective response rate (ORR) of 26 patients with EGFR mutations in LA-MPEs among the 36 patients with measurable lesions was 80.8%, while the ORR of the 10 patients with wild-type EGFR in LA-MPEs was 10% (p < 0.001). Among the 26 patients with EGFR mutations in LA-MPEs, the ORR of target lesions and LA-MPEs were 88.5% and 61.5%, respectively (p=0.026). Conclusion EGFR mutation status in cell blocks of LA-MPEs confirmed by pathologic diagnosis is highly predictive of EGFR TKI efficacy. For patients with EGFR mutations in LA-MPEs, the response to EGFR TKIs seems to be worse for pleural effusions than for solid tumors.

A Case of Pulmonary Langerhans Cell Sarcoma Simultaneously Diagnosed with Cutaneous Langerhans Cell Histiocytosis Studied by Whole-Exome Sequencing

Langerhans cell histiocytosis (LCH) and Langerhans cell sarcoma (LCS) are clonal proliferations of Langerhans-type cells. Unlike in LCH, the pathophysiology and clinical course of LCS are unclear due to its rarity. Here, we report the case of a 73-year-old male patient who was diagnosed with cutaneous LCH and pulmonary LCS at the same time. Pathological review of these 2 tumors revealed similar immunohistochemical findings. However, the tumor cells in LCS had more aggressive cytological features than those in LCH. Results of BRAF mutation analysis using real-time PCR were negative for both tumors. In whole-exome sequencing (WES), stop-gain mutations in TP53 gene were discovered only in LCS cells. The mechanism of development of LCS from various progenitor cells is currently unclear. According to the results of the WES study, changes in TP53 gene might have contributed to the malignant features of LCS.

Synchronous double primary renal cell carcinoma and duodenal adenocarcinoma

ogy, the incidence of double primary cancer is increasing. In case that one primary cancer was identified by pathologic finding and has suggestive multiple metastatic lesions of the cancer, it is often difficult that the lesions are considered as another synchronous primary malignancy, not as metastasis of primary cancer. Here, we report a rare case of synchronous double primary renal cell carcinoma that was diagnosed initially as metastatic duodenal adenocarcinoma. A 66-year-old man presented with a palpable abdominal mass. Abdominal computed tomography showed duodenal wall thickening and hypervascular masses in the liver and left kidney. Esophagogastroduodenoscopy revealed an ulcerative lesion in the duodenal bulb, and endoscopic biopsy identified moderately-differentiated adenocarcinoma. We regarded the findings as duodenal adenocarcinoma with metastasis to liver and kidney. So he was treated with fluoropyrimidine-based chemotherapy for the diagnosis of duodenal adenocarcinoma with liver and renal metastases. After 10 months, he developed a right forearm mass. Morphological and immunohistochemical analysis of an incisional biopsy of the forearm mass were consistent with a diagnosis of metastatic renal cell carcinoma. Even when there is a pathologically confirmed malignancy, clinicians must consider the possibility of synchronous double primary malignancy in metastatic lesions.