Chemotherapy is indispensable for the treatment of advanced biliary tract cancer. Recently, reports regarding first-line chemotherapy have increased, and first-line chemotherapy treatment has become gradually more sophisticated. Gemcitabine and cisplatin combination therapy (or gemcitabine and oxaliplatin combination therapy) have become the standard of care for advanced biliary tract cancer. Oral f luoropyrimidines have also been shown to have good antitumor effects. Gemcitabine, platinum compounds, and oral fluoropyrimidines are now considered key drugs for the treatment of advanced biliary tract cancer. Several clinical trials using molecular targeted agents are also ongoing. Combination therapy using cytotoxic agents and molecular-targeted agents has been evaluated widely. However, reports regarding second-line chemotherapy remain limited, and it has not yet been clarified whether second-line chemotherapy can improve the prognosis of advanced biliary tract cancer. Thus, there is an urgent need to establish secondline standard chemotherapy treatment for advanced biliary tract cancer. Several problems exist when assessing the results of previous reports concerning advanced biliary tract cancer. In the present review, the current status of the treatment of advanced biliary tract cancer is summarized, and several associated problems are indicated. These problems should be solved to achieve more sophisticated treatment of advanced biliary tract cancer.

Gastric cancer is the second most common cause of cancer death worldwide and is usually detected at a late stage, except in Korea and Japan where early screening is in effect. Results from animal and epidemiological studies suggest that Helicobacter pylori infection, and subsequent gastritis, promote development of gastric cancer in the infected mucosa. Relatively effective treatment regimens are available to treat H. pylori infection, and in general, mass eradication of the organism is not currently recommended as a gastric cancer prevention strategy. However, regional guidelines vary regarding the indications and recommendations for H. pylori treatment for gastric cancer prevention. In this review, we discuss the results from intervention studies, provide insight regarding current guideline recommendations, and discuss future study directions.

Background/Aims: Family history (FHx) of coronary heart disease (CHD) is a well-known risk factor for CHD. However, the prognostic implication of FHx has not been established clearly in patients with acute myocardial infarction (AMI). Methods: In total, 11,612 patients (8,132 males [70%], age $63{\pm}13$ years) with first-onset AMI between November 2005 and June 2008 in a nationwide, prospective, multicenter, online registry (the Korea AMI Registry) were analyzed. Clinical characteristics and outcomes (cardiac death and major adverse cardiac events [MACEs]) were assessed according to the presence of FHx. Results: The patients with FHx were younger and included more males. Male patients with FHx included more current smokers and individuals with poor lipid profiles. In all patients, after adjustment using the Cox proportional hazard model, FHx was related to the risk of MACEs (hazard ratio [HR], 1.41; p = 0.009) and cardiac death (HR, 1.56; p = 0.080). The poor prognostic implication of FHx was further augmented in females and a low risk subset of patients. A significant interaction was only found between male and female patients for composite MACEs (p for interaction = 0.057), and between patients with more risk factors (${\geq}2$ risk factors) and fewer risk factors for cardiac deaths (p for interaction = 0.008). Conclusions: FHx may be an independent prognostic predictor, especially in female patients and patients with low-risk profile.

Background/Aims: We investigated the clinical characteristics and follow-up findings of subjects with adrenal incidentalomas in a single, tertiary-care hospital in South Korea. Methods: The study consisted of a retrospective analysis of 282 adrenal incidentaloma patients who underwent radiographic and endocrinological evaluations at Samsung Medical Center in Seoul, South Korea, between January 2004 and July 2011. Results: Most (86.2%) of the subjects were found to have nonfunctioning tumors. Functioning tumors were seen in 39 patients (13.8%). Among them, 28 (9.9%) had subclinical Cushing syndrome (SCS), six (2.1%) had pheochromocytoma, and five (1.8%) had primary hyperaldosteronism. Malignant adrenal tumors were discovered in three cases: two (0.7%) were primary adrenal cancers, and one (0.4%) was a secondary metastasis from a lung cancer. Significant risk factors for functional tumors were female gender (odds ratio [OR], 3.386; 95% confidence interval [CI], 1.611 to 7.117; p = 0.0013) and a noncontrast attenuation value of > 10 Hounsfield units (OR, 2.806; 95% CI, 1.231 to 6.397; p = 0.0141). During follow-up (mean, 22.5 months) of 72 of the patients, three (4.2%) developed hormonal changes due to functional tumors. One was confirmed as pheochromocytoma by histopathology, and the others were diagnosed with SCS and followed routinely without surgical intervention. No malignant transformation was found in these patients. Conclusions: Based on these findings, initial hormonal and radiographic evaluations for adrenal incidentalomas appear to be more important than follow-up tests because functional or malignant changes are rare.

Background/Aims: In several recent studies, renal biopsies in patients with type 2 diabetes and renal disease have revealed a heterogeneous group of disease entities. Our aim was to study the prognosis and clinical course of nondiabetic renal disease (NDRD) and to determine risk factors for NDRD in patients with type 2 diabetes. Methods: Renal biopsy reports of 110 patients with type 2 diabetes who were seen at Kyung Hee University Medical Center and Kyung Hee University Hospital at Gangdong, Seoul, Korea between January 2000 and December 2011 were retrospectively analyzed. Results: Of 110 patients with type 2 diabetes, 41 (37.3%) had diabetic nephropathy (DN), 59 (53.6%) had NDRD, and 10 (9.1%) had NDRD superimposed on DN. Immunoglobulin A nephropathy (43.5%) was the most common NDRD. Patients with NDRD had a shorter duration of diabetes, lower frequency of diabetic retinopathy, and better renal outcomes, which might have resulted from the use of aggressive disease-specific treatments such as steroids and immunosuppressants in patients with NDRD. Conclusions: Compared with DN, NDRD was associated with better renal outcomes in patients with type 2 diabetes, as evidenced by a higher cumulative renal survival rate and lower rate of end-stage renal disease (ESRD). Shorter duration of diabetes and absence of retinopathy were independent predictors of NDRD in patients with type 2 diabetes and renal involvement. Renal biopsy is recommended for patients with type 2 diabetes and risk factors for NDRD, to obtain an accurate diagnosis, prompt initiation of disease-specific treatment, and ultimately better renal outcomes with the avoidance of ESRD.

Background/Aims: The higher incidence of gallbladder cancer (GBC) in females has been accredited to the involvement of hormones. The clinical implications of sex hormone receptors in GBC are well established. Cysteine proteases (such as caspase-3-9, etc.) are known to play a central role in the apoptotic pathway. Of these, the downstream enzyme caspase-3 is often activated in the apoptotic pathway. The aim of this work was to examine the status of apoptosis (which directly correlated with the level of active caspase-3) in hormone-responsive GBC. Methods: We used 10 androgen receptor (AR)-positive, 14 estrogen receptor (ER)-positive, 12 HER/neu-positive, eight triple positive, and 10 triple negative malignant GBC human tissue samples. We isolated the total cellular protein from tumor tissues and carried out Western blotting using antipro-caspase-3 and anti-activated caspase-3 antibodies. Results: ER and HER/neu-positive GBC exhibited high caspase-3 activity and low procaspase-3 activity, whereas AR-positive GBC showed no significant level of apoptosis. We also evaluated the apoptosis status of triple positive GBC and triple negative GBC, and found significant apoptosis in triple positive GBC. Conclusions: The results indicate that ER and HER/neu-positive GBCs had active apoptosis, whereas AR-positive GBC was highly resistant to apoptosis.

Background/Aims: Vitis vinifera grape seed extract (VVE) contains oligomeric proanthocyanidins that show antioxidant and free radical-scavenging activities. We evaluated VVE for its neuroprotective effect in prediabetic mice induce by a high-fat diet (HD). Methods: Mice were divided into four groups according to VVE dose: those fed a normal diet (ND; n = 10), HD (n = 10), HD with 100 mg/kg VVE (n = 10), and HD with 250 mg/kg VVE (n = 10). After 12 weeks, immunohistochemical analyses were carried out using a polyclonal antibody against antiprotein gene product 9.5 (protein-gene-product, 9.5), and intraepidermal innervation was subsequently quantified as nerve fiber abundance per unit length of epidermis (intraepidermal nerve fiber, IENF/mm). Results: Daily administration of VVE at doses of 100 or 250 mg/kg for 12 weeks protected HD mice from nerve fiber loss compared to untreated mice, as follows (IENF/mm): controls ($40.95{\pm}5.40$), HD ( $28.70{\pm}6.37$), HD with 100 mg/kg ($41.14{\pm}1.12$), and HD with 250 mg/kg ($48.98{\pm}7.01$ ; p < 0.05, HD with VVE vs. HD). Conclusions: This study provides scientific support for the therapeutic potential of VVE in peripheral neuropathy in an HD mouse model. Our results suggest that VVE could play a role in the management of peripheral neuropathy, similar to other antioxidants known to be beneficial for diabetic peripheral neuropathy.

Background/Aims: Encapsulating peritoneal sclerosis (EPS) is an often-fatal complication of long-term peritoneal dialysis (PD). We here report the clinical features of EPS in Korean PD patients from a single university center. Methods: The data were collected retrospectively from 606 PD patients at Kyungpook National University Hospital, between August 2001 and August 2011. The diagnosis of EPS was based on clinical signs and symptoms, and confirmed by radiological findings. Results: Eight patients (1.3%, four males) were diagnosed with EPS. The mean age of the patients was 48.5 years (range, 33 to 65). The mean duration of PD was 111.8 months (range, 23 to 186). All patients except for one had three or more episodes of peritonitis. Seven patients were diagnosed with EPS after stopping PD, and only one stayed on PD after initial diagnosis and treatment. Total parenteral nutrition and corticosteroids, in addition to tamoxifen therapy, were used to treat most of the patients, and one patient underwent surgery (adhesiolysis). The overall mortality rate was 50%. Conclusions: EPS is a serious, life-threatening complication in patients on longterm PD. To reduce the incidence and mortality rate of EPS, careful monitoring and early diagnosis is needed.

Background/Aims: Chronic arthritis of familial Mediterranean fever (FMF) involves weight-bearing joints and can occur in patients without a history of acute attack. Our aim was to investigate a possible causal relationship between FMF and osteoarthritis in a population in which FMF is quite common. Methods: Patients with late stage primary osteoarthritis were enrolled, and five MEFV gene mutations were investigated. The frequency of MEFV gene mutations was compared among patients with osteoarthritis and a previous healthy group from our center. Results: One hundred patients with primary osteoarthritis and 100 healthy controls were studied. The frequency of MEFV gene mutations was significantly lower in the osteoarthritis group (9% vs. 19%). M694V was the most frequent mutation (5%) in the osteoarthritis group, whereas in the control group, E148Q was the most common (16%). In subgroup analyses, the mutation frequency of patients with hip osteoarthritis was not different from that of patients with knee osteoarthritis and controls (7.1%, 9.7%, and 19%, respectively). There were no differences among the three groups with respect to MEFV gene mutations other than E148Q (8.1% vs. 3.6%). E148Q was significantly lower in the osteoarthritis group than in the controls (16% vs. 1%), although the mutations did not differ between patients with knee osteoarthritis and controls. Conclusions: In a population with a high prevalence of MEFV gene mutations, we did not find an increased mutation rate in patients with primary osteoarthritis. Furthermore, we found that some mutations were significantly less frequent in patients with osteoarthritis. Although the number of patients studied was insufficient to claim that E148Q gene mutation protects against osteoarthritis, the potential of this gene merits further investigation.

The solid pseudopapillary tumor (SPT) of the pancreas is a rare but low-grade malignant tumor with a good prognosis after surgical excision. Endoscopic ultrasound (EUS)-guided fine needle aspiration (FNA) is a minimally invasive, safe and reliable way of diagnosing SPT by providing characteristic cytological and immunochemical specimens. Definitive preoperative diagnosis leads to targeted and minimally invasive surgical resection. In this study, we report three cases of SPTs that were diagnosed through EUS-FNA and underwent successful laparoscopic surgery.

Dilated cardiomyopathy (DCM) is usually an idiopathic disease with a poor prognosis. Hypocalcemia is a rare and reversible cause of DCM. Here, we report a 50-year-old female with DCM, induced by idiopathic hypoparathyroidism, that improved after treatment with calcium.

We report the case of a patient who experienced extreme recurrent gestational hyperlipidemia. She was diagnosed with partial lipoprotein lipase (LPL) deficiency but without an associated LPL gene mutation in the presence of the apolipoprotein E3/2 genotype. This is the first reported case of extreme gestational hyperlipidemia with a partial LPL deficiency in the absence of an LPL gene mutation and the apolipoprotein E 3/2 genotype. She was managed with strict dietary control and medicated with omega-3 acid ethyl esters. A patient with extreme hyperlipidemia that is limited to the gestational period should be considered partially LPL-deficient. Extreme instances of hyperlipidemia increase the risk of acute pancreatitis, and the effect of parturition on declining plasma lipid levels can be immediate and dramatic. Therefore, decisions regarding the timing and route of delivery with extreme gestational hyperlipidemia are critical and should be made carefully.

Ankylosing spondylitis (AS) is a chronic inflammatory rheumatological disease affecting the axial skeleton with various extra-articular complications. Dysphagia due to a giant anterior osteophyte of the cervical spine in AS is extremely rare. We present a 48-year-old male with AS suffering from progressive dysphagia to soft foods and liquids. Esophagography showed an anterior osteophyte at C5-C6 resulting in esophageal compression. The patient refused surgical resection of the osteophyte and received conservative therapy. However, after 6 months there was no improvement in dysphagia. This case illustrates that a large cervical osteophyte may be the cause of dysphagia in patients with AS and should be included in the diagnostic workup in early stages of the disease.