Marginal zone B-cell lymphoma (MZL) is the second most common subtype of non-Hodgkin's lymphoma in Korea (17.3%). Mucosa-associated lymphoid tissue (MALT) can develop in almost any organ as a result of exposure to a persistent stimulus, such as chronic infection or certain autoimmune processes. Under conditions of prolonged lymphoid proliferation, a malignant clone may emerge, which is followed by the development of a MALT lymphoma. Whereas MALT lymphoma of the stomach is the most common and the most extensively studied, we focus on non-gastric MZL studies conducted in Korea that highlight the most recent advances with respect to MZL definition, etiology, clinical characteristics, natural history, treatment approaches, outcomes, and prognostic factors. Moreover, we discuss current organ-specific considerations and controversies, and identify areas for future research.

Background/Aims: Endoscopic papillary balloon dilation (EPBD) is a safe and effective method for the treatment of choledocholithiasis, but previous studies have rarely reported the appropriate ballooning time (BT). We prospectively evaluated the safety and efficacy of EPBD according to BT in patients undergoing bile duct stone removal. Methods: Seventy consecutive patients with bile duct stones were randomly assigned to receive EPBD with either conventional (n = 35, 60 seconds) or short (n = 35, 20 seconds) BT. Results: EPBD alone achieved complete bile duct clearance in 67 patients (long BT, n = 33, 94.3%; short BT, n = 34, 97.1%; p = 0.808). We also found no significant difference in the rate of complete duct clearance, including procedures that used mechanical lithotripsy, between the long and short BT groups (97.1% vs. 100%; p = 0.811). Mild pancreatitis was noted in four (11.4%) patients in the long BT group and two (5.7%) patients in the short BT group, but this incidence was not significantly different. Conclusions: The study showed that EPBD using both 20-sec and 60-sec BTs is safe and effective for the treatment of bile duct stones. Short and long BTs produced comparable outcomes.

Background/Aims: Few studies have assessed left ventricular (LV) dyssynchrony in cases of diastolic dysfunction that do not include overt symptoms of heart failure. We hypothesized that systolic or diastolic dyssynchrony involves unique features with respect to the degree of diastolic impairment in isolated diastolic dysfunction. Methods: We examined 105 subjects with no history of overt symptoms of heart failure and a left ventricular ejection fraction > 50% for mechanical dyssynchrony using tissue Doppler imaging. Results: In terms of longitudinal dyssynchrony, four cases showed (6.3%) LV intraventricular systolic dyssynchrony $(SDS_{LV})$, whereas none had LV intraventricular diastolic dyssynchrony $(DDS_{LV})$ or co-existing systolic dyssynchrony. Radial dyssynchrony (RD) was found in six cases (9.4%). After adjusting for age, $SDS_{LV}$ and $DDS_{LV}$ were found to be significantly related to increases in the E/$E^{\prime}$ ratio (r = 0.405 and p < 0.001 vs. r = 0.216 and p = 0.045, respectively). RD at the base and apex was also significantly related to increases in E/$E^{\prime}$ (r = 0.298 and p = 0.002 vs. r = 0.196 and p = 0.045, respectively). Conclusions: Systolic and diastolic dyssynchrony in subjects with isolated diastolic dysfunction but without overt symptoms of heart failure was not as common as in patients with diastolic heart failure; however, the systolic and diastolic intraventricular time delay increased with increases in the E/$E^{\prime}$ ratio, an indicator of diastolic dysfunction.

Background/Aims: In patients with heart failure (HF), N-terminal prohormone brain natriuretic peptide (NT-ProBNP) is a standard prognostic indicator. In addition, uric acid (UA) was recently established as a prognostic marker for poor outcome in chronic HF. The aim of this study was to determine the combined role of UA and NT-ProBNP as prognostic markers for short-term outcomes of acute heart failure (AHF). Methods: The levels of UA and NT-ProBNP were determined in 193 patients (age, $69{\pm}13$ years; 76 males) admitted with AHF. Patients were followed for 3 months and evaluated for cardiovascular events, defined as cardiac death and/or readmission for HF. Results: Of the 193 patients, 23 (11.9%) died and 20 (10.4%) were readmitted for HF during the 3-month followup period. Based on univariate analysis, possible predictors of short-term cardiovascular events were high levels of UA and NT-ProBNP, low creatinine clearance, no angiotensin converting enzyme inhibitors or angiotensin receptor blockers, and old age. Multivariate Cox hazard analysis showed that UA levels were independently associated with increased incidence of cardiovascular events (hazard ratio, 1.115; 95% confidence interval, 1.006 to 1.235; p = 0.037). Kaplan-Meier survival analysis revealed that patients with UA levels > 8.0 mg/dL and NT-ProBNP levels > 4,210 pg/mL were at highest risk for cardiac events (p = 0.01). Conclusions: The combination of UA and NT-ProBNP levels appears to be more useful than either marker alone as an independent predictor for short-term outcomes in patients with AHF.

Background/Aims: The usefulness of global longitudinal peak systolic strain (GLPSS) measurement by automated function imaging (AFI) in the prediction of perfusion status of infarct-related artery (IRA) before percutaneous coronary intervention (PCI) was evaluated. Methods: Sixty-nine patients with acute myocardial infarction (AMI) who underwent successful primary PCI were divided into two groups; the patients with occlusion of IRA (Group I, 41 patients, $63.0{\pm}14.9$ years of age, 31 males) versus the patients with patent IRA (Group II, 28 patients, $63.8{\pm}11.2$ years of age, 15 males). GLPSS by AFI and wall-motion score index (WMSI) were analyzed in both groups. Results: GLPSS was significantly decreased in Group I compared with Group II ($-11.2{\pm}3.7$ vs. $-14.1{\pm}4.7%$, p = 0.005), but WMSI ($1.49{\pm}0.28$ vs. $1.35{\pm}0.32$, p = 0.062) did not differ between groups. GLPSS of infarct segments was significantly lower ($-3.7{\pm}5.4$ vs. $-11.4{\pm}4.8%$, p < 0.001), and WMSI of infarct segments was significantly higher ($2.13{\pm}0.57$ vs. $1.66{\pm}0.57$, p = 0.001) in Group I compared with Group II. By receiver operation curve analysis, the area under the curve to predict IRA occlusion was 0.850 in GLPSS of infarct segments and 0.719 in WMSI of infarct segments. The optimal cut-off value to predict IRA occlusion was -9.4% in GLPSS of infarct segments (sensitivity, 85.4%; specificity, 67.9%) and 1.68 in WMSI of infarct segments (sensitivity, 78.0%; specificity, 60.7%). Conclusions: The present study suggested that GLPSS measured by AFI is a more sensitive predictor of IRA occlusion than is WMSI before PCI. Routine measurement of GLPSS by AFI can be a very useful tool in risk stratification of AMI.

Background/Aims: This study was conducted to examine the relationship between family history of type 2 diabetes (T2DM) and risk of developing gestational diabetes mellitus (GDM) in Korean women. Methods: We performed a 100-g oral glucose tolerance test in 858 pregnant women who had abnormal glucose tolerance in 50-g oral glucose challenge. In addition, we reviewed the incidence of T2DM in the parents and siblings and analyzed the association between the familial history of T2DM and the risk of GDM. Results: Of the 858 subjects, 427 were normal, and 431 were diagnosed with GDM. Compared with women with no family history of T2DM, women with first degree family history of T2DM displayed higher risk of T2DM (odd ratio: parent only 1.91, sibling only 6.24, any 2.27). Conclusions: The risk of developing GDM was significantly increased in Korean women with a family history of T2DM in first-degree relatives.

Background/Aims: Based on the results of well designed clinical studies, intensive insulin therapy has been established to improve glycemic control in newly diagnosed diabetes. However, discrepancies exist between the findings of clinical trials and experiences in general practice. Furthermore, the efficacy of an early insulin therapy (EIT) - commonly used in general practice - on long-term glycemic control has not been established. Therefore, we evaluated the effects of EIT on pancreatic ${\beta}$-cell function and glycemic control using insulin-based methods widely employed in general practice. Methods: We performed a retrospective cohort study that initially involved reviewing patients' medical records. Following a thorough review, 61 patients who received either biphasic or prandial EIT at the time of diagnosis were enrolled. We then evaluated changes in ${\beta}$-cell function and glycemic control during a 48-month follow-up period. Results: Mean HbA1c decreased significantly as a result of EIT from $10.7{\pm}1.8%$ to $6.2{\pm}1.1%$ (p < 0.001). On average, 2.6 months was required to achieve an HbA1c value < 7%. EIT significantly improved the insulinogenic index. Glycemic control was well maintained for 48 months. More than 70% of patients were able to maintain glycemic control following lifestyle modifications or treatment with oral antidiabetic drugs. No significant differences were identified between patients receiving biphasic EIT and prandial EIT in terms of glycemic control or pancreatic ${\beta}$-cell function. Conclusions: Our results suggest that regardless of the method of delivery, EIT significantly improves ${\beta}$-cell function and facilitates long-term glycemic control in patients with newly diagnosed type 2 diabetes mellitus.

Background/Aims: Based on preliminary in vitro data from a previous study, we proposed that 50 mg/kg glutathione (GSH) would be adequate for suppressing reactive oxygen species in patients with acute paraquat (PQ) intoxication. Methods: Serum levels of reactive oxygen metabolites (ROM) were measured before and after the administration of 50 mg/kg GSH to each of five patients with acute PQ intoxication. Results: In one patient, extremely high pretreatment ROM levels began to decrease prior to GSH administration. However, in the remaining four cases, ROM levels did not change significantly prior to GSH administration. ROM levels decreased significantly after GSH administration in all cases. In two cases, ROM levels decreased below that observed in the general population; one of these patients died after a cardiac arrest at 3 hours after PQ ingestion, while the other represented the sole survivor of PQ intoxication observed in this study. In the survivor, ROM levels decreased during the first 8 hours of GSH treatment, and finally dropped below the mean ROM level observed in the general population. Conclusions: Treatment with 50 mg/kg GSH significantly suppressed serum ROM levels in PQ-intoxicated patients. However, this dose was not sufficient to suppress ROM levels when the PQ concentration was extremely high.

Background/Aims: Kidney transplantations at our center rely mainly on living donors. The purpose of this study was to suggest future donor supply directions by reviewing changing trends in donor type. Methods: During the past 40 years, 1,690 kidney transplantations were performed at our center. We divided the follow-up period into four decades and the donor population into three groups: living related, living unrelated, and deceased. We analyzed changing trends in donors from each group for each decade. Patients receiving overseas transplantation were also included. Results: The proportion of living related donors decreased from 84% (54/64) in the 1970s to 61% (281/458) in the 2000s. Living unrelated donors showed a sustained proportion of around 20% after 1990. However, among living unrelated donors, the proportion of spouse donors increased from 4.6% (17/369) in the 1980s to 8.5% (39/458) in the 2000s. Transplants from deceased donors were only 3.3% (12/369) in the 1980s. However the proportion of deceased donors increased gradually, reaching 13.2% (105/799) in the 1990s and 19.9% (91/458) after 2000. Overseas transplantations increased after 2000 and reached 20% of all cases treated in our center during the 2000s. Such transplantations peaked in 2006 and decreased markedly thereafter. Conclusions: The proportion of each donor type has continuously changed, and the changes were associated with changes in the social structure and system. We expect that this study could be an important reference for other countries to estimate future changes of donor type.

Background/Aims: The efficacy and safety of pemetrexed, gefitinib, and erlotinib administration in previously treated patients with non-small cell lung cancer (NSCLC) were compared. Methods: The study patients met the following criteria: histologically confirmed, previously treated advanced (stage IIIB or IV) or recurrent NSCLC; a measurable lesion; ${\geq}$ 18 years of age; Eastern Cooperative Oncology Group Performance status 0 to 2; and no prior exposure to the three study drugs. Patients received 500 mg/$m^2$ of pemetrexed intravenously every 3 weeks with vitamin supplementation, gefitinib (250 mg/day per os), or erlotinib (150 mg/day per os). Results: Of 57 patients (pemetrexed, 20; gefitinib, 20; and erlotinib, 17), 55 were evaluated for a response. The numbers of males, smokers, and squamous histology were increased in the pemetrexed group compared to the other groups. The objective response rates were 5.3%, 25.0%, and 12.5% (p = 0.22), and the disease control rates (DCR) were 5.3%, 40.0%, and 50.0%, respectively (p < 0.01). The median progression-free survival (PFS) was 1.7, 3.5, and 4.4 months (p < 0.01) and the median overall survival (OS) was 5.6, 21.8, and 21.5 months (p = 0.04), respectively. In subgroup analyses, patients with non-squamous histology, males, and a smoking history had a higher DCR and longer PFS with gefitinib and erlotinib than with pemetrexed. All three chemotherapeutic agents had manageable toxicities. Conclusions: Both oral epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) had comparable efficacy and safety. The superior PFS and OS of EGFR TKIs with more favorable baseline clinical characteristics than those of pemetrexed suggest the impact of baseline clinicopathological factors.

Background/Aims: Rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy (R-CHOP) has improved survival in patients with diffuse large B-cell lymphoma (DLBCL) and weakened the prognostic power of the international prognostic index (IPI). We evaluated the efficacy of the IPI and revised IPI (R-IPI) in patients with DLBCL who were treated with R-CHOP, focusing on extranodal site number (ENS) because extranodal involvement occurs frequently in Koreans. Methods: A total of 126 R-CHOP-treated patients with stage III/IV DLBCL were analyzed. We performed a retrospective analysis of the clinicopathologic factors and verified the predictive power of the standard IPI and RIPI. Various numbers of extranodal sites were analyzed for further stratification, and we set the extranodal sitemodified IPI (E-IPI) as the IPI when the number of extranodal sites was stratified as < 3 vs. ${\geq}$ 3. Results: A univariate analysis showed that ENS was associated with complete response (CR, p = 0.04), eventfree survival (EFS, p = 0.01), and overall survival (OS, p < 0.001) when the ENS cut-off was set at ≥ 3. A multivariate analysis revealed that an ENS ${\geq}$ 3 remained associated with EFS (p < 0.01; hazard ratio [HR], 2.60; 95% confidence interval [CI], 1.29 to 5.26) and OS (p < 0.01; HR, 3.52; 95% CI, 1.68 to 7.35). The IPI was effective for determining prognosis in terms of OS (p = 0.04) but not EFS (p = 0.17). The R-IPI was effective in terms of both variables (p = 0.02 and 0.04, respectively), as was the E-IPI (p = 0.01 and 0.001, respectively). Conclusions: An ENS < 3 vs. ${\geq}$ 3, rather than the original < 2 vs. ${\geq}$ 2, was the most significant prognostic factor for EFS and OS. All three indices were predictive, but only the E-IPI identified the high-risk group of R-CHOP-treated Korean patients with disseminated DLBCL.

Background/Aims: Many patients with aspirin-induced asthma have severe methacholine airway hyperresponsiveness (AHR), suggesting a relationship between aspirin and methacholine in airway response. This study was performed to determine whether methacholine AHR affects the response of asthmatics to inhaled aspirin. Methods: The clinical records of 207 asthmatic patients who underwent inhalation challenges with both aspirin and methacholine were reviewed retrospectively. An oral aspirin challenge was performed in patients with a negative inhalation response. The bronchial reactivity index (BRindex) was calculated from the percent decrease in lung function divided by the last dose of the stimulus. Results: Forty-one (20.9%) and 14 (7.1%) patients showed a positive response to aspirin following an inhalation and oral challenge, respectively. Only 24.3 and 14.3% of the responders had a history of aspirin intolerance, respectively. The methacholine BRindex was significantly higher in the inhalation responders $(1.46{\pm}0.02)$ than in the oral responders ($1.36{\pm}0.03$, p < 0.01) and in non-responders (n = 141, $1.37{\pm}0.01$, p < 0.001). The aspirin BRindex was significantly correlated with the methacholine BRindex (r = 0.270, p < 0.001). Three of four patients who received the oral challenge, despite a positive inhalation test, showed negative responses to the oral challenge. Two of these patients had severe AHR. Conclusions: A considerable number of asthmatic patients with no history of aspirin intolerance responded to the inhalation aspirin challenge. The airway response to aspirin was significantly correlated with methacholine AHR, and a false-positive response to aspirin inhalation test seemed to occur primarily in patients with severe AHR.

Background/Aims: This study was undertaken to identify the intracellular signaling pathway involved in induction of macrophage migration inhibitory factor (MIF) in human rheumatoid arthritis (RA) synovial fibroblasts. Methods: Human RA synovial fibroblasts were treated with concanavalin A (ConA), various cytokines, and inhibitors of signal transduction molecules. The production of MIF by synovial fibroblasts was measured in culture supernatants by ELISA. The expression of MIF mRNA was determined using reverse transcriptase polymerase chain reaction (RT-PCR) and real-time PCR. Phosphorylation of p38 mitogen-activated protein (MAP) kinase in synovial fibroblasts was confirmed using Western blotting. The expression of MIF and p38 MAP kinase in RA synovium was determined using dual immunohistochemistry. Results: The production of MIF by RA synovial fibroblasts increased in a dose-dependent manner after ConA stimulation. MIF was also induced by interferon-${\gamma}$, CD40 ligand, interleukin-15, interleukin-$1{\beta}$, tumor necrosis factor-${\alpha}$, and transforming growth factor-${\beta}$. The production of MIF by RA synovial fibroblasts was significantly reduced after inhibition of p38 MAP kinase. The expression of MIF and p38 MAP kinase was upregulated in the RA synovium compared with the osteoarthritis synovium. Conclusions: These results suggest that MIF production was induced through a p38 MAP-kinase-dependent pathway in RA synovial fibroblasts.

A right-sided aortic arch (RAA) is a rare congenital anomaly, and Stanford type B dissection aneurysms involving this anomaly is also uncommon. Surgical approaches to dealing with an RAA are complicated by the unusual anatomical features of the condition. Here we report the case of a 47-year-old male who had a type B dissecting aneurysm involving an RAA with Kommerell's diverticulum. Graft replacement was successfully performed with an uneventful postoperative course.

We experienced a case of primary pulmonary biphasic synovial sarcoma, which was confirmed by immunohistochemistry and molecular testing of SYT-SSX2 fusion transcripts. The patient was a 61-year-old man who presented with a well-defined mass in the left upper lung field on chest radiography. Left upper lobectomy with lymph node dissection was performed. Histological and immunophenotypic features were consistent with biphasic synovial sarcoma. Reverse transcriptase polymerase chain reaction, performed using RNA extracted from frozen tumor samples for the detection of SYT-SSX fusion gene, amplified a single 331-bp fragment that was characteristic of the SYT-SSX2 fusion transcripts. We report a case of primary pulmonary biphasic synovial sarcoma, which was confirmed by SYT-SSX2 fusion transcripts, and present a brief review of the literature on Korean cases.

We describe here a patient who obtained a good analgesic effect with high-dose fentanyl patches for controlling cancer pain. A 52-year-old man was referred to our hospital because of severe cancer pain that was 7/10 on a numeric rating scale (NRS). He had been diagnosed with locally advanced cholangiocarcinoma 3 months previously. We prescribed weak opioids and an antidepressant, but his pain was not relieved. We introduced strong opioids (transdermal fentanyl patches for the background pain and a short-acting opioid for the breakthrough pain) and his pain was tolerable on 250 ${\mu}g$/hr of fentanyl patches for 3 months. With time, however, his pain intensity became worse and this reached up to 8/10 to 9/10 on the NRS. Percutaneous transhepatic biliary drainage was performed, which did not relieve his pain. We increased gradually the dose of transdermal fentanyl to 1,050 ${\mu}g$/hr (20 patches). At this dose, the patient was mentally alert, with good pain control (NRS 2/10 to 3/10) and no exacerbation of side effects. To the best of our knowledge, we report here on the highest dose of transdermal fentanyl that has been successfully used for treating a patient suffering from visceral cancer pain.

The variability of cardiovascular abnormalities is one of the characteristics of systemic lupus erythematosus (SLE). Among the cardiovascular manifestations, hypertension is reported in 14% to 58.1% of patients in diverse ethnic populations, and remains a clinically important issue due to its close relationship with early mortality in patients with SLE. The development of hypertension in patients with SLE has been associated with advanced lupus-related renal disease and the medications used for the treatment of lupus. Malignant hypertension is a serious complication of hypertension; it rarely occurs in patients with SLE. However, it can occur in patients with other complicated medical conditions such as the antiphospholipid antibody syndrome (APS) or cardiac tamponade. Here, we report the case of a patient with SLE and malignant hypertension with hypertensive retinopathy that initially presented without clinical evidence of APS or hypertensive nephropathy.