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The vascular complications have been a major cause of morbidity and mortality among all subtypes of BCR-ABL1 negative myeloproliferative neoplasms (MPN), but the ethnicity-specific data was limited. We therefore conducted a multi-center retrospective, longitudinal cohort study to evaluate the incidence, characteristics and risk factors of thromboembolic events of MPN patients. Of 256 patients, 27.3% experienced thromboembolic events, majority of which occurred before or within 12 months of MPN diagnosis. The multivariable Cox proportional analyses identified leukocytosis (HR 2.67, 95% CI 1.36–5.24, q = 0.004) and history of thrombosis (HR 9.68, 95% CI 2.00–46.88, q = 0.005) as the risk factors for thromboembolism. In subgroup analysis of polycythemia vera and hemoglobin concentration (HR 1.97, 95% CI 1.28–3.04, q = 0.002) appeared to be a significant risk factor of thrombosis, along with age and thrombosis history. In essential thrombocythemia, severity of the established IPSET score was closely correlated with the frequency of thromboembolic events. In primary myelofibrosis, history of thrombosis was associated with thrombosis events (HR 13.85, 95% CI 1.2–159.5, q = 0.035). Overall survival was worse in patients who experienced thromboembolic events. Our study highlighted the importance of recognizing high risk patients and implementing personalized intervention.

Objectives Transforming growth factor‐beta (TGF‐β) is a multifunctional regulatory factor. Here we measured serum soluble TGF‐β (sTGF‐β) levels and evaluated its dynamics and prognostic capabilities during chemotherapy in unresectable pancreatic cancer patients. Methods We prospectively enrolled 60 patients treated with FOLFIRINOX as the first‐line palliative chemotherapy. We collected blood samples at the time of diagnosis, first response assessment, and disease progression and measured serum sTGF‐β using an enzyme‐linked immunosorbent assay. Results The patients’ median overall survival (OS) and progression‐free survival (PFS) were 10.3 (95% confidence interval [CI], 8.5‐12.1) and 6.5 (95% CI, 4.9‐8.1) months, respectively. Patients with low sTGF‐β at diagnosis (, Pre‐treatment sTGF‐β levels serve as a prognostic indicator in unresectable pancreatic cancer patients treated with FOLFIRINOX chemotherapy. The dynamics of sTGF‐β during chemotherapy have prognostic value.

Background: Traditionally believed to be an integral part of multiple myeloma (MM) treatment, the role of hematopoietic stem-cell transplantation (HSCT) is being challenged. As such, we sought to evaluate the impact of HSCT in the era of novel agents. Methods: A multicenter, retrospective, longitudinal cohort study was carried out between January 2016 and December 2018. A total of 55 patients who received VTD (bortezomib-thalidomide-dexamethasone) as first-line treatment and KRd (carfilzomib-lenalidomide-dexamethasone) as second-line treatment were analyzed for outcomes. Results: The enrolled patients were divided into Group 1, defined as those who continued KRd treatment until progression ( n = 41), versus Group 2, defined as those who underwent HSCT after a certain number of cycles of KRd ( n = 14). Both groups showed a generally favorable response to KRd, with overall response rate (ORR) of 87.9% and clinical benefit rate of 92.8% after a median of seven cycles in Group 1, and ORR 92.8% and clinical benefit rate 100% after median of five cycles in Group 2. However, significantly poorer progression-free survival (PFS) ( p = 0.004) was observed in Group 1 (median 12 months) compared with Group 2 (median not reached). Multivariate analyses identified HSCT after KRd as potential risk factors associated with PFS. Also, in Group 1, bortezomib refractoriness was associated with significantly shorter PFS compared with those who were responsive (median 12 months versus 14 months, respectively, p = 0.039). Conclusions: In conclusion, even with the advent of novel agents, HSCT still remains a valuable treatment modality with additive efficacy.

Background AL amyloidosis might increase the risk of thromboembolism and other plasma cell dyscrasias; however, only a few reports have described the clinical features of thromboembolism. The present study aimed to elucidate the clinical features of thromboembolic events and to identify the risk factors for these events. Materials and Methods The medical records were retrospectively reviewed to define the clinically significant thromboembolic events. Results A total of 106 patients with biopsy-proven AL amyloidosis were included. During a median follow-up of 18.1 months (range, 0.4-166.9 months), 13 thromboembolism events were identified in 13 patients. Of the 13 patients, 9 (8.5%) experienced acute cerebral infarction, 2 (1.9%) experienced pulmonary embolism, and 2 (1.9%) experienced deep vein thrombosis. Patients with a higher serum free light chain (FLC) difference (≥ 172.4 mg/L) or β 2 -microglobulin (β2MG) levels (≥ 2.78 mg/L) experienced significantly more thromboembolic events compared with those with a lower value according to multivariable analysis (for FLC difference: hazard ratio, 4.309; 95% confidence interval, 1.158-16.032; P = .029; for β2MG: hazard ratio, 9.739; 95% confidence interval, 1.127-84.174; P = .039). Most thromboembolic events (11 of 13; 84.6%) occurred within the first year after the AL amyloidosis diagnosis. Conclusion The incidence of thromboembolism was substantial in those with AL amyloidosis. A greater FLC difference and for β2MG levels were risk factors for thromboembolic events.

Infection is one of the main causes of early-treatment mortality in multiple myeloma (MM) patients during autologous stem cell transplantation (autoSCT). In the present study, we sought to determine the incidence of, and risk factors for, infection during hospital stays after autoSCT. We retrospectively evaluated 324 autoSCT events that occurred in 285 MM patients between 2006 and 2015, and reviewed the clinical characteristics of patients and history of infections. Sixty-eight infection events occurred, including bacteremia (24), other bacterial infections (7), as well as infections caused by Cytomegalovirus (17), Herpes simplex virus (12), Varicella zoster virus (3), Aspergillus (3) and Pneumocystis jiroveci (2). There was no significant difference in number of infections in the 2006-2010 and 2011-2015 periods (P = 0.194). Risk factors for bacteremia included higher beta-2 microglobulin levels at diagnosis [≥3.5 mg/L; adjusted odds ratio (aOR) 3.544 (95% CI 1.070-11.736), P = 0.038] and previous bortezomib treatment [aOR 4.270 (95% CI 1.389-13.125), P = 0.011]. In-hospital mortality occurred in 1.2% of all cases and all were infection-related. In conclusion, infection was the main cause of in-hospital mortality in patients who underwent autoSCT. Bacteremia was the most common type of microbiologically confirmed infection, and was associated with higher beta-2 microglobulin levels and previous bortezomib treatment.

// Kyoung-Min Cho 1, 3 , Hyunkyung Park 1 , Do-Youn Oh 1, 2 , Tae-Yong Kim 1 , Kyung Hun Lee 1, 2 , Sae-Won Han 1, 2 , Seock-Ah Im 1, 2 , Tae-You Kim 1, 2 and Yung-Jue Bang 1, 2 1 Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea 2 Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea 3 Department of Internal Medicine, Graduate School, Kyung Hee University, Seoul, Republic of Korea Correspondence to: Do-Youn Oh, email: ohdoyoun@snu.ac.kr Keywords: biliary tract cancer, skeletal muscle depletion, weight change, BMI, prognosis Received: December 28, 2016 Accepted: May 22, 2017 Published: June 02, 2017 ABSTRACT Background: No prior study has investigated the dynamics of body weight with body muscle mass as a prognostic factor in advanced biliary tract cancer (BTC) patients undergoing palliative chemotherapy. We investigated whether low skeletal muscle mass affects survival in patients with BTC, with a co-analysis of body weight loss and body mass index (BMI). Results: By multivariate analysis, low skeletal muscle mass at diagnosis and decreased SMI during chemotherapy ( p = 0.008 and p < 0.001, respectively) were poor prognostic factors for overall survival (OS). Subgroup analysis revealed that low skeletal muscle mass patients who were overweight or obese (BMI ≥ 25 kg/m 2 ) showed worse OS ( p < 0.001). Additionally, patients with both decreased BMI and SMI during chemotherapy had worse OS ( p < 0.001). Furthermore, patients with decreased SMI had shorter survival regardless of change in BMI. However, for patients with SMI maintained during chemotherapy, decreased BMI had no effect on survival ( p = 0.576). Materials and Methods: We consecutively enrolled 524 patients with advanced BTC who received palliative chemotherapy between 2003 and 2013. Total muscle cross-sectional area (cm 2 ) at the L3 level assessed by computed tomography was analyzed. We defined low skeletal muscle mass as a skeletal muscle index (SMI) < 48.5 cm 2 /m 2 (men) and < 39.5 cm 2 /m 2 (women) using ROC curves. Conclusions: Low skeletal muscle mass, obesity and muscle depletion during palliative chemotherapy are meaningful prognostic factors in advanced BTC. Considering muscle depletion with weight change could help to more accurately predict prognoses of patients with BTC.

Background In an experimental animal model of islet transplantation, stable induction of insulin-dependent diabetes mellitus (IDDM) and islet isolation from donor pancreas are essential. Total pancreatectomy for IDDM induction and islet procurement in nonhuman primates leads to unwanted loss of exocrine function and may lead to morbidities associated with IDDM. Methods IDDM induction with streptozotocin (STZ) is associated with drug toxicity of STZ and necessitates the killing of another animal for islet procurement. In this study, we performed a subtotal pancreatectomy combined with reduced STZ injection to induce IDDM and procure islets in a nonhuman primate model. Results Twelve cynomolgus monkeys received low-dose STZ injections (60 mg/kg) simultaneously with subtotal pancreatectomy. All monkeys recovered from the procedure without complications. IDDM was induced in the animals. 57,691 ± 16,050 islets were isolated from the resected pancreas and transplanted into other monkeys. Conclusions Simultaneous subtotal pancreatectomy and low-dose STZ injection represent an effective and safe method to create an animal model of insulin dependence diabetes, while at the same time providing sufficient amounts of fresh islet cells for allotransplantation without requiring killing of additional animals.

Background/Aims We explored Korean physicians’ policies for surveillance of colorectal cancer (CRC) after curative surgery. Methods Web-based self-report questionnaires were developed. Invitations to participate were emailed to physicians who diagnosed and treated CRC from October 1 to November 15, 2015. The questionnaire consisted of the role doctors played in the surveillance, examination of surveillance, and duration of postoperative surveillance according to CRC stage or primary site of the cancer. Results Ninety-one physicians participated in the online survey, and 78 completed the survey. Sixty-seven participants (13%) answered “up to 5 years” for stage I surveillance duration; and 11 (13%) responded with a duration of > 5 years for stage I. A total of 61 (75%) responded with a surveillance duration of up to 5 years for stage II; and 19 (24%) responded with a duration of > 5 years for stage II. Sixty-seven (97%) and 61 (91%) physicians monitored patients with stage II/III every 3 or 6 months by laboratory examination and by abdominopelvic computed tomography scan for the first year, respectively. A total of 43 (53%) responded with a surveillance duration of up to 5 years for stage IV; and 46 (46%) responded with a duration of > 5 years for stage IV after curative resection. Conclusions Korean physicians mostly followed up CRC using intensive postoperative surveillance. In preference to monitoring over a comparatively shorter period of time, the physicians tended to prefer monitoring patients post-operatively over a > 5 year period, particularly in cases of advanced-stage CRC.

Contamination of fresh vegetables and berries with human enteric viruses is a major cause of food poisoning. The aim of this study was to investigate the prevalence of norovirus GI, norovirus GII, hepatitis A virus (HAV), adenovirus, astrovirus, rotavirus, and male-specific coliphage systematically in fresh fruit and vegetables and associated agricultural environmental samples, including irrigation water, soil, and worker's gloves. Enteric viruses were detected by international standard methods (ISO/TS 15216), and male-specific coliphages were isolated using US EPA Method 1601. For the study, 773 samples were collected from June 2016 to April 2017, including Chinese cabbage (n = 244), cucumber (n = 98), lettuce (n = 73), strawberry (n = 120), soil (n = 191), irrigation water (n = 14), and gloves (n = 27). Two cucumber and two irrigation water samples were positive for norovirus GI, and one cucumber and two irrigation water samples were positive for norovirus GII. HAV was detected in one strawberry sample and one glove sample. The other tested foodborne viruses were not detected in any of the samples. Sixteen male-specific coliphages were isolated from Chinese cabbage, cucumber, lettuce, cherry tomato, soil, and irrigation water. The isolation of male-specific coliphage would be more practical to investigate the fecal contamination in produce rather than pathogenic viruses.

Tumor thrombus is a unique characteristic of renal cell carcinoma (RCC). However, only a few studies have reported its clinical influence on the occurrence of venous thromboembolism (VTE). This study aimed to clarify the influence of tumor thrombus and other risk factors for VTE and to elucidate the impact of tumor thrombus on survival outcomes. We retrospectively reviewed data from patients with RCC who underwent radical or partial nephrectomy from September 1999 to August 2015 at Seoul National University Hospital. A total of 2762 patients were enrolled. The 1- and 5-year cumulative incidences of VTE were 0.5% ± 0.1% and 1.5% ± 0.3%, respectively. During a median follow-up of 39.0 months (95% confidence interval [CI], 37.1-41.0 months), deep vein thrombosis occurred in 13 patients and pulmonary embolism in 15 patients. Patients with tumor thrombus (diagnosed by surgical pathology findings) had a significantly higher incidence of VTE than those without thrombus (odds radio 8.160, 95% CI, 1.480-45.004). Older age (≥60 years) and higher preoperative C-reactive protein (>0.5 mg/dL) were also significant risk factors for VTE. Additionally, tumor thrombus was independently associated with worse progression-free survival (PFS) but not with overall survival (OS) in multivariable analysis (hazard ratio [HR] 1.916, 95% CI, 1.295-2.834 for PFS; HR 1.164, 95% CI, 0.755-1.793 for OS). In conclusion, the incidence of VTE was relatively low in patients who underwent surgery for RCC. Nevertheless, patients with tumor thrombus had an increased risk of VTE and should be closely monitored for VTE.

Radiation-induced cavernous malformations (RICMs) are most commonly reported in young patients who have previously received radiotherapy. Here, we report a case of a patient with a germ cell tumor who was treated with whole brain radiotherapy (WBRT) and then incidentally found to have numerous RICMs. A 31-year-old male visited the hospital for a testicular mass. On examination, he was diagnosed with a mixed germ cell tumor with lung/brain metastases. The patient underwent a left orchiectomy and received 4 cycles of chemotherapy. He was then treated with WBRT for residual lesions in the brain and a wedge resection for the lung metastasis. Four years later, approximately 250-300 RICMs were incidentally observed in a follow-up brain image. Because the patient had not noticed any symptoms and the RICMs were small in size, he was not treated. To our knowledge, this is the first reported case of numerous (approximately 250-300) RICMs in a germ cell tumor patient after WBRT. Herein, we report details of this case and discuss the typical clinical features of RICM.

Background Several studies have suggested potential links of phthalates to obesity in children and adults. Limited evidence, however, has been available for the relations between diethylhexyl phthalate (DEHP) and obesity-related markers or body mass change in early life. Methods 128 healthy pregnant women were recruited and, after delivery, their newborns’ first urine and umbilical cord blood samples were collected. We measured urinary levels of two DEHP metabolites, mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) and mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP). We also measured the levels of leptin, total cholesterol and triglyceride (TG) in cord serum, and used them along with weight, length, head circumference and ponderal index (PI, 100 g/cm 3 ) at birth, as obesity-related markers, and estimated the relations between DEHP metabolites and obesity-related markers using generalised linear models. For the evaluation of body mass increase by early life DEHP exposure, body mass index (BMI) z-score change during 3 months after birth by DEHP metabolites in the first urine samples of the newborns were evaluated using logistic regression. Results DEHP exposure was associated with decrease of PI and increase of TG (PI, β=−0.11, p=0.070 and TG, β=0.14, p=0.027), especially for boys (PI, β=−0.13, p=0.021; and TG, β=0.19, p=0.025). Moreover, DEHP exposure was positively associated with body mass increase during 3 months after birth (change of BMI z-scores, OR=4.35, p=0.025). Conclusions Our findings suggest that DEHP exposure may affect body mass change in early life through changes of obesity-related markers.

Background: Despite offering an attractive option, the role of allogeneic stem cell transplantation (alloSCT) for treatment of multiple myeloma (MM) remains unclear. Methods: Recognizing the paucity of data in the Asian population, we retrospectively evaluated the outcomes of 24 patients (median age 52) undergoing alloSCT between April 2003 and November 2017. Results: The median time from diagnosis to alloSCT was 39.4 months. The majority of the patients (70.8%) underwent alloSCT followed by reduced intensity conditioning regimens after a median of five lines of therapy. Among 24 patients, 15 patients (62.5%) had a high-risk MM feature. The two-year relapse-free survival (RFS) and overall survival (OS) of the total patients were 29.2 ± 9.3% and 44.3 ± 10.3%, respectively. Patients who were treated with less chemotherapy lines (

Background/Aims Atrophic gastritis (AG) and intestinal metaplasia (IM) are premalignant gastric lesions. The aims of this study were to evaluate the prevalence of endoscopic AG and IM and to document the risk factors for these lesions. Methods In total, 4,023 subjects were enrolled at eight hospitals in Korea. AG and IM were diagnosed by endoscopy. Helicobacter pylori immunoglobulin G antibodies were measured. Results The prevalences of endoscopic AG and IM were 40.7% and 12.5%. In a multivariate analysis, the risk factors for AG were age groups of 40 to 59 years and >60 years, male sex, positive H. pylori serology, IM, and education below the college level (odds ratio [OR], 2.55, 5.00, 1.38, 1.41, 4.29, and 1.35, respectively). The risk factors for IM were age groups of 40 to 59 years and >60 years, male sex, positive H. pylori serology, AG, having relatives with gastric cancer, education below the college level and consumption of dairy products (OR, 3.16, 3.25, 1.88, 2.17, 3.68, 1.48, 1.47, and 1.40, respectively). Conclusions A nationwide survey regarding the prevalence of endoscopic AG and IM and their risk factors in Korea supports the hypothesis that endoscopic diagnosis of these premalignant lesions could be helpful to describe a group at high risk for gastric cancer.

Background and purpose We investigated the effect of celecoxib, a selective inhibitor of cyclo-oxygenase 2, in patients with intracerebral hemorrhage (ICH). Methods We conducted a multicenter, randomized, controlled, and open with blinded end-point trial of 44 Korean patients 18 years or older with ICH within 24 h of onset. The intervention group (n = 20) received celecoxib (400 mg twice a day) for 14 days. The control group (n = 24) received the standard medical treatment for ICH. The primary end-point was the number of patients with a change in the volume of perihematomal edema (PHE) from the 1st to the 7th ± 1 day (cut-off value, 20%). Results The time from onset to computed tomography scan slightly differed between groups (177 ± 160 min for control vs. 297 ± 305 min for the celecoxib group; P = 0.10). In the primary end-point analysis using cut-off values, there was a significant shift to reduced expansion of PHE in the celecoxib group (P = 0.005). With respect to the secondary end-points, there was also a significant shift to reduced expansion of ICH in the celecoxib group (P = 0.046). In addition, the expansion rate of PHE at follow-up tended to be higher in the control group than in the celecoxib group (90.6 ± 91.7% vs. 44.4 ± 64.9%; P = 0.058). Conclusions In our small, pilot trial, administration of celecoxib in the acute stage of ICH was associated with a smaller expansion of PHE than that observed in controls.

BACKGROUND/AIMS Gastroesophageal reflux disease is one of the most common and frequent chronic disease requiring considerable cost. We investigated the medical care costs in the erosive reflux disease (ERD) and non-erosive reflux disease (NERD). METHODS The risk factors and the direct medical care costs were analyzed retrospectively in the ERD (178 patients) and NERD (183 patients) groups for a follow up period of 2 years. RESULTS Logistic regression analysis showed that the ERD was more frequent in the groups of male gender, alcohol consumption, higher body mass index (>/=25 kg/m(2)), hiatal hernia, and higher triglyceride levels (>/=150 mg/dL). The direct medical care costs per person for 2 years were found to be $384.8 (ERD) and $412.9 (NERD) without statistically significant differences (p = 0.364). However, 9.3% (17/183) of the NERD patients had visited the emergency room compared to 3.4% (6/178) of the ERD patients (p = 0.029). In addition, more NERD patients were hospitalized than ERD patients (p = 0.006), and because of the longer hospitalization period, the medical costs in NERD patients were higher than ERD patients (p = 0.038). CONCLUSIONS In spite of the different risk factors for ERD and NERD, total direct medical care costs were similar between the ERD and NERD group. However, more visits to emergency room and longer hospitalization period with more hospitalization costs in NERD patients account for the differences in medical service and usage distribution between the 2 groups.

We investigated how the quantity of p15INK4b methylation related to International Prognosic Scoring System variables and survival in 74 patients with de novo myelodysplastic syndrome (MDS). Pyrosequencing of 11 consecutive CpG sites of the p15INK4b promotor region was performed, with the extent of CpG cytosine methylation assessed in terms of methylation level (MtL). Patients with5% bone marrow blasts had higher MtL than patients with5% blasts (10.1% vs. 6.1%, p=0.030, respectively). Methylation was not associated with chromosomal aberrations. The MtL of patients with thrombocytopenia were higher than patients without thrombocytopenia (11.2% vs. 6.2%, p=0.036, respectively); they were higher in patients with cytopenias inor =2 lineages than in patients with either unilineage or no cytopenia (9.8% vs. 4.1%, p=0.036, respectively). The survival of patients with7% MtL was worse than patients with7% MtL (p=0.031). Heavy p15INK4b methylation in MDS is associated with IPSS predictors of poor prognosis and adverse survival.

We evaluated the usefulness of dual priming oligonucleotide (DPO)-based multiplex PCR, Seeplex HBV Lami-DR assay (Seegene Institute of Life Sciences, Seoul, Korea), to detect lamivudine-resistant HBV mutants in a comparison with the use of TRUGENE™ HBV genotyping and restriction fragment mass polymorphism (RFMP). Sera from 44 chronic hepatitis B patients were analyzed for the presence of mutations at codons 180 and 204 by performing DPO-based multiplex PCR, RFMP, and TRUGENE. The overall concordance rate among the three assays was 40.9% (18/44). Concordance rates between multiplex PCR and RFMP or multiplex PCR and TRUGENE were 61.4% (27/44) and 50.0% (22/44), respectively. In ten patients, multiplex PCR identified additional mutants not found using the other two methods. DPO-based multiplex PCR is a highly sensitive method to identify minor mutant populations and could be a practical tool in the monitoring of lamivudine resistance.

Pulmonary lymphoma is a very rare cause of lung tumors which occurs in less than one percent of primary malignant lung tumors. When seemingly pneumonia does not respond to treatment, the possibility of malignant lymphoma should always be considered. Here, we report two cases of pulmonary lymphoma misdiagnosed as pneumonia.

Background/aims Colonic diverticular bleeding cases account for 30-40% of the lower gastrointestinal bleeding, among which, 3-5% appear to be massive bleeding. The purpose of this study was to evaluate the risk factors for colonic diverticular bleeding diagnosed by colonoscopic examination. Methods Among the 1,003 patients, who were identified to have colonic diverticulosis including sleeding by diverticulitis and diverticular bleeding coding search, 216 patients had diverculosis, and they were divided into two groups: one with diverticular bleeding, and the other without bleeding. We evaluated the potential risk factors for diverticular bleeding, based on age, gender, location of diverticulum, comorbidities related to atherosclerosis, smoking, alcohol and medications, and compared them between both groups. Results Among the 216 patients, we observed colonic diverticular bleeding in 35 patients (16.2%). The mean age of the bleeding group was significantly older than that of non-bleeding group. No difference was observed regarding gender ratio. Right colonic diverticula were common in both groups, but there were higher proportion of patients with bleeding in bilateral diverticuosis. Old age, bilateral diverticulosis, presence of atherosclerosis related diseases (hypertension, diabetes mellitus, ischemic heart disease, obesity), use of aspirin, NSAIDs and calcium channel blocker, increased the risk of bleeding. In a multivariate analysis, use of aspirin and bilateral diverticulosis were identified as independent risk factors for colonic diverticular bleeding. Conclusions Since the patients who took aspirin and/or had bilateral colonic diverticulosis increased the risk of bleeding from divertuculi. As such, caution and education of patients are required.

411 Background: Host antitumor immunity measured by neutrophil-lymphocyte ratio (NLR) is reported to be associated with prognosis of cancer patients. Standard uptake value (SUV)by18F-FDG PET represents the metabolic activity of tumor itself. The correlation of host immunity and tumor metabolic activity has not been studied. We investigate the association of these two factors and evaluate their roles in prediction of overall survival (OS) in metastatic pancreatic cancer (MPC) patients who receive palliative chemotherapy. Methods: We reviewed 396 MPC patients receivingpalliative chemotherapy. NLR was obtained before initiation of chemotherapy and after 1st cycle of chemotherapy. In 118 patients who were evaluated with 18F-FDG PET before initiation of chemotherapy (PET cohort), maximum SUV (SUVmax) was collected. Cut-offs for each variable were determined by ROC curve. Results: In multivariate analysis, higher NLR was associated with worse OS ( < 2.5, 9.0 m; 2.5-4.4, 7.2 m; ≥ 4.5, 3.9 m; p< 0.001). Reduction of NLR after 1st cycle of chemotherapywas associated with betterOS (8.0 m vs 6.1 m; HR 0.653; p< 0.001). We made the risk scoring model considering both NLR (score 0, NLR < 2.5; score 1, 2.5 ≤ NLR < 4.5; score 2, NLR ≥ 4.5) and ΔNLR(score 0:ΔNLR < 0; score 1: ΔNLR ≥ 0), which identified 4 risk groups with different prognosis (group with risk score 0 vs 1 vs 2 vs 3: OS 9.7 vs 7.9 vs 5.7 vs 2.6 months; HR 1 vs 1.329 vs 2.137 vs 7.915, respectively; P < 0.001). In PET cohort (118 patients), NLR and SUVmax were independent prognostic factors for OS. The risk model considering both NLR (score 0, NLR < 2.5; score 1, 2.5 ≤ NLR < 4.5; score 2, NLR ≥ 4.5) and SUVmax (score 0:SUVmax < 4.5; score 1: SUVmax ≥ 4.5), which define 4 risk groups with different OS. (group with risk score 0 vs 1 vs 2 vs 3: OS 11.8 vs 9.8 vs 7.2 vs 4.6 months; HR 1 vs 1.536 vs 2.958 vs 5.336, respectively; P < 0.001). Conclusions: NLR and SUVmax as simple parameters of host antitumor immunity and tumor metabolic activity, respectively, have significant impacts on the survival of metastatic pancreatic cancer patients independently. Consideration of both aspects allows more precise prediction of patients’ prognosis.

Currarino syndrome (CS) is a rare autosomal dominant disease that has been described as a triad of partial sacral agenesis, anorectal anomalies, and a presacral mass. Mutations in the HLXB9 gene have been suggested to be the genetic background of CS. In this study, sequence analysis of the HLXB9 gene was performed in two familial and two sporadic Korean patients showing the clinical features of CS, and two mutations in the HLXB9 gene were identified only in the two familial cases. One mutation (R295W) has been reported previously, and the other (H260_Q261delinsLELLELE) is novel. Consistent with previous observations, the phenotypic expression of the mutation carriers in the CS families varies from mild to severe, including the complete triad. This study confirms that familial CS patients in Korea have the same genetic background as other ethnicities and reaffirms the phenotype variability among CS patients with the same mutation.

Aim: There has been little report about the long-term results of AI in adjuvant treatment of the breast cancer from Asian countries.This observational study (NCT:00913016) was performed to evaluate the long-term effect of letrozole (Femara®) in Korean women with operable breast cancer. Methods: Self-reported Quality of Life (QoL) scores during adjuvant letrozole treatment was serially assessed using Korean version of the Functional Assessment of Cancer Therapy-Breast (FACT-B) questionnaires (version 3) for 3 years. We also analyzed the change of bone mineral density (BMD) and serum cholesterol level during adjuvant letrozole treatment. Eight hundred and ninety-seven women from 32 institutes participated in the study. Results: All the 897 patients received documented informed consent form to participate in the study and completed a baseline questionnaire before adjuvant letrozole trearment. Seventy percent (n = 624) underwent adjuvant chemotherapy. Forty hundred and ten (45.8%) had stage 1 breast cancer and 396 (44.3%) had stage 2 disease. Follow-up questionnaires were completed by individual patient without help of medical person before the patients visited the clinician at 3, 6, 12, 18, 24, 30, and 36 months after the entry to the study. Of total 897 patient, 749 patients (83.5%) completed the study. Drop-out rate was 16.5%. Main reasons of dropout were recurrence of breast cancer (n = 35; 3.9%), severe arthralgia (n = 41; 4.5%) and follow-up loss (n = 52; 5.9%). The serial trial outcome index (TOI) which is the sum of the physical, functional well-being and breast cancer specific subscales was gradually and significantly increased from baseline during the letrozole treatment (p Conclusions: The QoL was gradually improved during the letrozole treatment. Changing profiles of BMD and serum cholesterol level was not different from those of western countries. The results of this study indicate that adjuvant letrozole treatment is well tolerated in Korean women with minimal ethnic variation. Disclosure: All authors have declared no conflicts of interest.

Abstract 3793 Poster Board III-729 Introduction The inactivation of tumor suppressor genes by promotor hypermethylation, particularly p15INK4b, is believed to contribute to the initiation and the progression of myelodysplastic syndromes (MDS). p15INK4b methylation was found to be more frequent in high-risk MDS (RAEB) at the time of diagnosis, and to be associated with progression to AML in the studies using methylation-specific PCR (MSPCR). We investigated if the quantity of p15INK4b methylation is related to International Prognosic Scoring System variables (IPSS) and survival in the myelodysplastic syndrome (MDS) patients and if the quantity of p15INK4b methylation reflects the bone marrow status (the percentage of blasts or the degree of dysplasia) of the patients under treatment with or without hypomethylating agents. Materials and Methods The study included 74 de novo MDS patients including 24 with follow-up bone marrow examination: 10 under treatment with hypomethylating agent and 14 under treatment with other than hypomethylating agent including stem cell transplantation (SCT). We pyrosequenced 63 base pairs of p15INK4b including 11 CpGs using PSQ96MA system (Biotage, Uppsala, Sweden), with the extent of CpG cytosine methylation assessed in terms of methylation index (MtI) and methylation level (MtL). Result Patients with >5% bone marrow blasts had higher MtI and MtL (58.8% and 10.1%, respectively) than patients with 50% MtI or >7% MtL was worse than patients with Conclusion Using pyrosequencing, we showed that the quantity of p15INK4b methylation correlates with thrombocytopenia and blast percentage in MDS patients. Heavy p15INK4b methylation in MDS is associated with adverse survival. Methylation quantity of p15INK4b did not appear to reflect the bone marrow status of the patients under treatment regardless of the use of hypomethylating agent in this study, however, further study with controlled patient group is required to clarify this issue. Fig. 1. Heavy methylation of the p15INK4b promotor region is a prognostic factor for poor survival in MDS patients. (a) Kaplan-Meier curves of MDS patients with MtI >50% and patients with MtI 7% and patients with MtL Disclosures: No relevant conflicts of interest to declare.

The gain of the 1q region, which is a recurrent chromosomal aberration in B lymphoproliferative disorder, has been reported one of the most common anomalies in Korean myelodysplastic patients. Recently, risk based application of hypomethylating agents or tailored therapy in MDS rely on the prognostic variables of International Prognostic Scoring System (IPSS). To investigate the possibility of 1q gain as a new prognostic marker, we evaluated the prognostic impact of 1q gain, along with comparison with IPSS variables. A total of 117 patients with newly diagnosed MDS between 1997 and 2007 at the Seoul National University Hospital were investigated. Fluorescence in situ hybridization (FISH) studies with 5 specific probe(EGR1 for 5q31 deletion, D7S522 for 7q31 deletion, CEP8, D20S108 for 20q12 deletion, LSI 1p36/1q25 for 1q gain) and conventional G-banding karyotyping were performed on bone marrow aspirates. Other laboratory findings, such as hemoglobin(Hb), absolute neutrophil count(ANC), platelet count, bone marrow blast percent and IPSS score, and clinical data were collected through the individual medical records. The median age was 54 years and the male-to-female ratio was 1.4. Using WHO classification, refractory anemia(RA) was 27.4% and the other subgroups as follows: RA with ringed sideroblast(RARS), 3.4%; refractory cytopenia with multilineage dysplasia(RCMD), 8.5%; RCMD with ringed sideroblasts(RCMD-RS), 0.9%; RA with excess blasts-1(RAEB-1), 26.5%; RAEB-2, 31.6%; and 5q- syndrome, 1.7%. Cytogenetic abnormalities by FISH and G-banding were detected in 58 patients (49.6%). Most frequent anomaly was trisomy 8 occuring in 28 patients(23.9% of the 117 patients, 48.3% of the 58 patients with clonal cytogenetic abnormalities). Gain of 1q was the second common anomalies seen in 18 patients (15.4%) and other anomalies were −7/del7q (13.7%), −5/del5q (13.7%), and del20q (2.6%). G-banding showed gain of 1q in 7 cases, additional 11 patients with gain of 1q were revealed by FISH only. Patients with 1q gain showed a poor survival (median survival 23 months; n=18) compared to patients without 1q gain (median survival 60 months; p=0.02). EGR1 and D7S522 deletion by FISH also had a shorter median survival (8 months vs. 60 months p=0.0001, 16 months vs. 60 months p=0.005). The initial platelet count and blast count were found to affect overall survival, whereas CEP8 FISH, D20S108 FISH, Hb and ANC did not. Our results show that gain of 1q is associated with an adverse clinical outcome and can be considered as a poor cytogenetic risk factor of IPSS. In the Western study, the prevalence of 1q gain was low because most studies report G-banding result only. But it may be increased up to 2.5 fold higher by using FISH analysis in combination with G-banding. A gain of 1q could be a candidate as an adverse prognostic marker in clinical practice, which could help for risk-adapted therapies. Figure 1. Kaplan-Meier survival curve for chromosomal anomalies and IPSS. (A) gain of 1q. (B) −1/del(7q). (C) del(20q). Figure 1. Kaplan-Meier survival curve for chromosomal anomalies and IPSS. (A) gain of 1q. (B) −1/del(7q). (C) del(20q).

Although mutations in three genes, amyloid precursor protein (APP), presenilin 1 (PSEN1), and presenilin 2 (PSEN2), have been identified as genetic causes of early-onset Alzheimer s disease (EOAD), there has been a single report on a PSEN1 mutation in Koreans. In the present study, we performed a genetic analysis of six Korean patients with EOAD. Direct sequencing analysis of the APP, PSEN1 and PSEN2 genes revealed two different mutations of the PSEN1 gene (G206S and M233T) and one mutation of the APP gene (V715M) in three patients with age-at-onset of 34, 35, and 42 yr, respectively. In addition, two patients with age-at-onset of 55 and 62 yr, respectively, were homozygous for APOE epsilon 4 allele. One woman had no genetic alterations. These findings suggest that PSEN1 and APP gene mutations may not be uncommon in Korean patients with EOAD and that genetic analysis should be provided to EOAD patients not only for the identification of their genetic causes but also for the appropriate genetic counseling.

9715 Background: Epidemiologic studies indicated that nonsteroidal antiinflammatory drugs can reduce the risk of breast cancer, possibly via cyclooxygenase(COX) inhibition. The growth factor-inducible COX-2, which is overexpressed in neoplastic tissue, is attractive target of cancer treatment. Methods: We evaluated the relationships between COX-2 overexpression, Her-2/neu overexpression, and clinicopathological features in 112 Korean breast cancer patients. Protein expression was analysed by immunohistochemical stain in paraffin embedded tissues using monoclonal antibody for COX-2 and Her-2/neu. To explore the role of selective COX-2 inhibitor, celecoxib, and humanized anti-Her-2/neu monoclonal antibody trastuzumab in vitro, MTT assay of the breast cancer cells which have different expression levels of the COX-2 and Her-2/neu protein (MCF 7, COX-2 -, Her-2/neu -; MCF 7/H18, COX-2 -, Her-2/neu +; SKBR-3, COX-2 weak +, Her-2/neu +) were studied and a cell cycle analysis was performed. Results: Increased COX...