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Background and aims Segregated right intrahepatic duct dilatation (IHD) results from complete obstruction of the biliary tract proximal to the hilar level. We aimed to evaluate long-term efficacy and safety of endoscopic ultrasound (EUS) hepaticoduodenostomy (HDS) in segregated right IHD. Methods Consecutive patients who had undergone EUS-guided HDS with a fully covered self-expandable metal stent (FCSEMS) in an academic tertiary center were recruited. All patients had segregated right hepatic duct and failed drainage by endoscopic retrograde cholangiopancreatography (ERCP). Demographic data, endoscopic findings, procedure details, and outcome data were extracted from a prospectively maintained database. Results From 2013 to 2017, there were 35 patients who had undergone EUS-guided HDS with a median follow-up duration of 169 (3-2091) days. Malignancy accounted for 71.4% of the ductal segregation, followed by surgical complication (17.1%). Technical and clinical success rate was 97.1% and 80%, respectively. Early adverse event (AE) happened in seven patients (20%), two of them required endoscopic reintervention, and no percutaneous transhepatic biliary drainage (PTBD) or surgery was performed because of AE. The median stent patency duration was 331 (3-1202) days. The median duration of fistula tract keeping was 1280 (3-1280) days. There was no significant difference in terms of patency rate with respect to whether the underlying pathology was benign or malignant (P = 0.776). EUS-guided HDS for right posterior sectional duct segregation was associated with higher 3-month stent patency rate when compared with right anterior sectional duct (79.1% vs 38.1%, P = 0.012). Conclusion Endoscopic ultrasound-guided HDS with an FCSEMS appears to be a safe and effective treatment as a viable alternative option to PTBD after failed ERCP. It creates a durable and reliable fistula tract for permanent access to an isolated ductal system, and this application deserves more attention.

Endoscopic gallbladder drainage (GBD) has been performed as an alternative to percutaneous drainage for acute cholecystitis. To date, there has been no comparative study between EUS-guided cholecystostomy (EUSC) and endoscopic transpapillary cholecystostomy (ETC). The aim of this study was to compare the outcomes of EUSC and ETC.A retrospective review of an endoscopic GBD database prospectively collected at the Asan Medical Center (between July 2010 and December 2014) was performed to identify consecutive patients with acute cholecystitis who underwent attempted endoscopic GBD. Procedural and long-term outcomes were evaluated using inverse probability of treatment weighting (IPTW).A total of 172 patients (76 in the EUSC group and 96 in the ETC group) were included in this study. Seven patients who failed to undergo ETC crossed over to the EUSC group. After adjustment with the IPTW method, technical success (99.3% vs 86.6%, P .01) and clinical success (99.3% vs 86%, P .01) rates were significantly higher in the EUSC group than in the ETC group. The procedure-related adverse event rate was significantly higher in the ETC group (7.1% vs 19.3%, P = .02). The cholecystitis or cholangitis recurrence rate (12.4% vs 3.2%) was also higher in the ETC group than in the EUSC group, as identified using Cox analysis (hazard ratio, 3.01; 95% confidence interval, .73-12.9; P = .04).In patients with acute cholecystitis who are unfit for surgery, EUSC may be a more suitable treatment method than ETC.

Endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) is increasingly accepted as an effective treatment option in patients who require drainage for acute cholecystitis. A newly designed lumen-apposing metal stent (LAMS) has been introduced recently in this procedure. In this study, we evaluated the feasibility and safety of the newly designed LAMS in patients with acute cholecystitis who were unsuitable for cholecystectomy. Between Mar 2017 and Oct 2017, 22 patients with acute cholecystitis who were unsuitable for cholecystectomy underwent EUS-GBD with the newly designed LAMS. We evaluated the technical and clinical success and the adverse event profiles. EUS-GBD with newly designed LAMS was technically and clinically successful in 21 of the 22 patients. EUS-GB stenting was performed at urgent setting in 17 patients, while 5 patients, who had undergone initial PTGBD, underwent EUS-GB stenting to remove PTGBD tube. The median procedure time was 11.5 (range 8.8–17.0) min. A late adverse event of stent occlusion developed in one patient. Stent migration was not observed during follow-up (median 318.0 days, range 39.0–398.0 days) and cumulative stent patency rate at 1 year was 95%. EUS-GBD with newly designed LAMS is feasible and shows acceptable safety profiles for both the urgent drainage of acute cholecystitis and elective internalization following PTGBD in patients with high surgical risk.

Axillary nodal status is one of the most important prognostic factors in breast cancer. The lymph node ratio (LNR) has been suggested as an independent prognostic factor because the number of dissected and involved lymph nodes might differ across institutions. Neoadjuvant chemotherapy (NAC) has been the preferred treatment method for reducing tumor mass in the breast and axillary area. However, NAC can reduce total number of excised lymph nodes compared with upfront surgery. Therefore, an emerging question is whether axillary nodal status and LNR following NAC can accurately predict prognosis. We evaluated the prognostic value of axillary nodal status and LNR after NAC. A total of 236 patients were enrolled. Patients were divided into four groups according to the following cut-off values for LNR: 0 (n = 107), 0.01–0.20 (n = 68), 0.21–0.65 (n = 50) and >0.65 (n = 11). Pathologic complete responses were observed in 16.9% of the overall cohort. In univariate analysis, pathologic N stage was a significant prognostic factor of disease free survival (DFS, p = 0.013) and overall survival (OS, p = 0.004). However, in multivariate analysis, hormone receptor status (p = 0.043) and LNR (p = 0.028) were significantly associated with DFS and LNR (p = 0.017) showed statistical significance for OS; however, pathologic N stage was no longer significantly associated with DFS or OS. Traditional nodal staging has been accepted as an important prognostic factor; however, our result indicated that the nodal ratio could be an alternative to pN staging as a prognostic factor after NAC in breast cancer. Keywords: Axilla, Breast, Neoadjuvant therapy, Lymph node, Survival

Type 1 autoimmune pancreatitis (AIP), as a pancreatic manifestation of IgG4-related disease, shows a favorable prognosis in the short term. However, disease relapse is common in long-term follow-up, despite a successful initial treatment response. This study aimed to identify the predictors of relapse and long-term outcomes in patients with type 1 AIP. Patients with more than 2 years of follow-up who met the International Consensus Diagnostic Criteria for type 1 AIP were included. Patients who had undergone pancreatic operations associated with AIP or who lacked sufficient clinical data were excluded. All 138 patients achieved clinical remission with initial steroid therapy, and 66 (47.8%) experienced relapse during a median 60 (range 24–197) months follow-up. Among the relapsed patients, about 74% (49/66) relapsed within 3 years. About 60% (82/138) had other organ involvement (OOI), most commonly in the proximal bile duct (26.8%). At first diagnosis, OOI, and especially OOI of the proximal bile duct, was a significant independent predictor of relapse (hazard ratio 2.65; 95% confidence interval 1.44–4.89; p = 0.002), according to multivariate analysis. During the follow-up period, 16 (11.6%) patients experienced endocrine/exocrine dysfunction and 32 (23.2%) patients developed de novo pancreatic calcifications/stones. No pancreatic cancer occurred in any patients. Type 1 AIP has common relapses, and patients with OOI, especially OOI of the proximal bile duct, appear to be at increased risk for relapse. Long-term sequelae, including pancreatic insufficiency and pancreatic calcifications/stones, are common in patients with relapse. To reduce the relapse, longer maintenance treatment may be needed especially for patients at high risk for relapse.

Background and Aims Although fully covered self-expandable metal stents (FCSEMSs) have been commonly used for EUS-guided biliary drainage (EUS-BD), FCSEMS migration is a main limitation of this procedure. In the present study we evaluated the technical and clinical success rates, adverse events, and long-term outcomes of a newly developed hybrid stent that has been customized for EUS-BD. Methods From September 2011 to May 2015, 54 consecutive patients with biliary obstruction were enrolled in this prospective, observational study. These patients were candidates for alternative BD techniques because of failed ERCP. The hybrid metal stent used for EUS-BD in this study was partially covered, had anchoring flaps, and is commercially available in Korea. Results EUS-guided hepaticogastrostomy (EUS-HGS) was performed in 21 patients and EUS-guided choledochoduodenostomy (EUS-CDS) in 33 patients. The technical and clinical success rates of EUS-BD were 100% (54/54) and 94.4% (51/54), respectively. Immediate adverse events developed after EUS-BD in 9 patients (16.6%; cholangitis in 3, bleeding in 2, self-limited pneumoperitoneum in 3, and abdominal pain in 1). Proximal or distal stent migration was not observed during the follow-up period (median, 148.5 days; IQR, 79.7-244), and the mean stent patency duration was 166.3 days and 329.1 days in the EUS-HGS and EUS-CDS groups, respectively. Conclusions EUS-BD with the hybrid metal stent is technically feasible and can effectively treat biliary obstruction after failed ERCP. EUS-BD with the hybrid metal stent can reduce stent-related adverse events, especially stent migration.

Background and aims Acute necrotizing pancreatitis (ANP) can affect main pancreatic duct (MPD) as well as parenchyma. However, the incidence and outcomes of MPD disruption has not been well studied in the setting of ANP. Methods This retrospective study investigated 84 of 465 patients with ANP who underwent magnetic resonance cholangiopancreatography and/or endoscopic retrograde cholangiopancreatography. The MPD disruption group was subclassified into complete and partial disruption. Results MPD disruption was documented in 38% (32/84) of the ANP patients. Extensive necrosis, enlarging/refractory pancreatic fluid collections (PFCs), persistence of amylase-rich output from percutaneous drainage, and amylase-rich ascites/pleural effusion were more frequently associated with MPD disruption. Hospital stay was prolonged (mean 55 vs. 29 days) and recurrence of PFCs (41% vs. 14%) was more frequent in the MPD disruption group, although mortality did not differ between ANP patients with and without MPD disruption. Subgroup analysis between complete disruption (n = 14) and partial disruption (n = 18) revealed a more frequent association of extensive necrosis and full-thickness glandular necrosis with complete disruption. The success rate of endoscopic transpapillary pancreatic stenting across the stricture site was lower in complete disruption (20% vs. 92%). Patients with complete MPD disruption also showed a high rate of PFC recurrence (71% vs. 17%) and required surgery more often (43% vs. 6%). Conclusions MPD disruption is not uncommon in patients with ANP with clinical suspicion on ductal disruption. Associated MPD disruption may influence morbidity, but not mortality of patients with ANP. Complete MPD disruption is often treated by surgery, whereas partial MPD disruption can be managed successfully with endoscopic transpapillary stenting and/or transmural drainage. Further prospective studies are needed to study these items.

IgG4-related sclerosing cholangitis (IgG4-SC) represents a rare but clinically challenging differential diagnosis in patients with biliary strictures which can be mistaken for cholangiocarcinoma. We present a case of a 73-year-old male presented with abdominal discomfort and weight loss. Biliary images showed long-segment luminal narrowing of extrahepatic bile duct associated with prominent enhanced wall thickening, but luminal patency was preserved. Pancreatic images revealed segmental irregular narrowing of main pancreatic duct without upstream duct dilatation. His liver function tests and CA19-9 level were normal. Putting all findings together, IgG4-SC associated with autoimmune pancreatitis was strongly suspected. However, endobiliary biopsy of extrahepatic bile duct revealed adenocarcinoma which was not resectable due to celiac axis involvement. Because there is an overlap in biliary imaging findings between IgG4-SC and cholangiocarcinoma, biopsy is essential for adequate differential diagnosis. We present a case of cholangiocarcinoma masquerading as IgG4-SC based on clinical and imaging findings.

Recent research has shown that a substantial number of patients with primary sclerosing cholangitis (PSC) can also have elevated serum/tissue IgG4. The aim of our study was to develop a simple scoring system for the discrimination of IgG4-related sclerosing cholangits (IgG4-SC) from PSC. Patients with IgG4-SC (n = 39) and PSC (n = 76) who had intrahepatic/hilar strictures were included. Candidate-differentiating variables included patient age, other organ involvement (OOI), inflammatory bowel disease, serum IgG4, and cholangiographic features. A scoring system was developed on the basis of these variables, and its performance was internally validated using a bootstrapping-based method. The scoring system in the final model included age (

Acute recurrent pancreatitis (ARP) refers to a clinical condition characterized by repeated episodes of acute pancreatitis, diagnosed retrospectively after at least the second episode of acute pancreatitis. It is still controversial that acute pancreatitis can progress to chronic pancreatitis, and acute, acute recurrent and chronic pancreatitis is a continuum of disease. The causes of ARP can be divided into mechanical, hereditary and metabolic factor. Despite recent advances in diagnostic technologies, the etiology of ARP still remains unknown in up to 30% of cases. Especially in recurrent episode of idiopathic pancreatitis, a clinician should be considered not only the common causes of ARP, such as gallstone disease and alcohol, but also rare causes of ARP. The common causes of ‘idiopathic’ recurrent pancreatitis are microlithiasis, sludge, sphincter of oddi dysfunction, pancreas divisum and hereditary pancreatitis. Various treatment options, such as cholecystectomy, endoscopic sphincterotomy, medical and surgery can be applied according to the identified etiology of ARP and treatment should be individualized. Currently, endoscopic treatment is increasingly performed and served as a curative treatment strategy. The medical treatment can be an option in microlithiasis and sludge, but it has limitation in terms of systemic side effect, efficacy and lack of long term outcome. Endoscopic treatment should be considered in selected patients with identifiable cause, and post procedural complication should be considered before endoscopic treatment. Korean J Pancreatobiliary 2016;21(1):1-10

Background/objectives The pancreatoduodenal groove (anatomical groove) is a potential space bordered by the head of the pancreas, duodenum, and common bile duct. Discerning between groove carcinoma (GC) and groove pancreatitis (GP) is often difficult, but clinically important. We retrospectively analyzed and compared the findings of computed tomography (CT), laboratory tests, and endoscopic ultrasound-fine needle aspiration (EUS-FNA) for GC and GP. Methods GC (n = 36) and GP (n = 44) patients at Asan Medical Center from January 1, 2000, to May 31, 2017 were retrospectively reviewed. MDCT findings, baseline characteristics, laboratory test results, and EUS and EUS-FNA findings of GC and GP patients were compared. Results CT showed no significant difference in groove enhancement between the groups. Mass-like lesions, cystic groove lesions, and calcification were observed in 86.1% and 15.9%, 38.9% and 75%, and 2.8% and 29.5% of GC and GP patients, respectively. Patients were tested for total bilirubin (GC: 2.0 vs. GP: 0.6 mg/dL), cancer antigen 19-9 (CA19-9) (GC: 76 vs. GP: 12.5 U/mL), and carcinoembryonic antigen (GC: 2.4 vs. GP: 2 ng/mL). Three GP patients died, and one GP patient was diagnosed with GC. However, among 30 GC patients with at least 1-year follow-up, 20 died. In multivariate logistic regression, CA19-9, and mass-like lesion on multidetector CT (MDCT) were discriminating factors between GC and GP. Among 23 (10 GC, 13 GP) patients who underwent EUS-FNA, the diagnostic sensitivity, specificity, positive predictive value, negative predictive value, accuracy of EUS-FNA were 90%, 100%, 100%, 92.86%, and 95.65%, respectively. Conclusions Several MDCT and laboratory findings favor GC over GP. EUS-FNA should be considered in patients with elevated CA19-9 levels and mass-like lesions on MDCT.

BACKGROUND AND AIM Endoscopic snare papillectomy (ESP) is an effective treatment for ampullary adenoma. Argon plasma coagulation (APC) is widely used as an additional method to control bleeding or ablate the residual tumor. However, the efficacy of this procedure has not yet been fully evaluated. This study aimed to evaluate the usefulness of APC as an additional method to ESP. METHODS Patients who underwent ESP for ampullary adenoma between September 2005 and September 2015 were retrospectively reviewed. Using propensity score matching, we compared short- and long-term outcomes between the ESP-with-additional-APC group (ESP + APC group) and the ESP-only group. Primary outcome was early post-ESP adverse events (AE), and secondary outcomes were late AE and recurrence. RESULTS Among 109 patients, additional APC was carried out in 59 (54.1%) patients. After matching, 41 patients were included in both groups, respectively. Bleeding rate was significantly lower in the ESP + APC group than in the ESP-only group (7.3% vs 31.7%, odds ratio = 0.180, P

Purpose Peripheral neuropathy (PN) is known as a major contributor of the worsening of ischemic symptoms and the foot ulceration in patients with peripheral arterial occlusive disease (PAOD). However, there are few studies reporting the prevalence and risk factors for PN in PAOD. This study aimed to evaluate these issues for PN and to establish the importance of screening as additional treatment target for PN in PAOD. Materials and methods A total of 52 limbs with PAOD were enrolled from January 2011 to December 2012. PN was divided into radiculopathy, ischemic PN (IPN), and diabetic PN (DPN), based on electromyographic findings. We investigated the prevalence of overall PN and subtypes of PN and then analyzed the risk factors. Results The prevalence of overall PN in PAOD was 43 of 52 limbs (82.7%). In terms of subtypes of PN, the prevalence rate of radiculopathy and IPN was 30.8% and 23.1%, respectively. DPN showed in 22 limbs (73.3%) among 30 diabetic limbs. There was no significant correlation between each type of PN and ischemic symptoms. Our analysis showed that coronary artery disease (CAD) was a significant risk factor (P=0.01) for IPN, however, did not identify any significant risk factors for DPN. Conclusion This present study indicated that most patients with PAOD had PN and CAD was a risk factor for IPN. In particular, PAOD with diabetes represented a higher prevalence for DPN. Our study suggests that PN should be evaluated and considered as another treatment target in patients with PAOD.

Purpose: We evaluated the adequacy and feasibility of a tumescent solution containing lidocaine and bupivacaine for inguinal hernia repairs. Methods: The medical records of 146 consecutive inguinal hernia patients with 157 hernia repairs using the tumescent local anesthesia technique performed by a single surgeon between September 2009 and December 2013 were retrospectively reviewed. Results: The mean operation time (±standard deviation) and hospital stay were 64.5 ± 17.6 minutes and 2.7 ±1 .5 days. The postoperative complication rate was 17.8%. There were four cases of recurrences (2.5%) at a mean follow-up of 24 ± 14 months. Conclusion: Our results suggest that local anesthesia with the tumescent technique is an effective and safe modality for inguinal hernia repairs.

Background: We evaluated the value of neutrophil-lymphocyte count ratio (NLCR) in patients admitted to the Emergency Department (ED) with suspected nursing home acquired pneumonia (NHAP) Methods: From May 2011 to January 2013, 116 patients admitted to the ED with suspected NHAP were retrospectively studied. The clinical characteristics, C-reactive protein (CRP), white blood cell count, neutrophil count, lymphocyte count, and NLCR were assessed. CURB-65 score was used to calculate disease severity. General ward or intensive care unit (ICU) admissions, and 72-hour and 30-day mortality for each infection marker was assessed. Results: The 116 patients had a median age of 77 years. As the CURB-65 score increased from 0-1 (low risk), to 2-3 (moderate risk), and to 4-5 (high risk), the NLCR consistently increased (mean, 6.9, 8.89, and 16.22, respectively). The difference between the moderate and high risk groups was significant (p=0.008). The NLCR (mean±standard deviation) was high in patients with NHAP (10.28±8.81) and increased even more for patients admitted to the ICU (15.69 ±14.81) or who died within 72-hour (15.63±9.57). NLCR showed the trend of higher value in ICU admission (p=0.072), and CRP was significantly different between ICU and general ward admission (p=0.007). Conclusion: NLCR at ED admission correlated with NHAP severity and was comparable to the traditional infection marker. NLCR can be assessed simply and added to the assessment tools to determine the severity of pneumonia during ED admission.

Occult breast cancer is a type of breast cancer without any symptoms on the breasts or any abnormalities upon radiologic examination such as mammography. In males, there are few cases of breast cancer, the rate of diagnosis of occult breast cancer is very low, and little is known about this disease. We experienced two cases of occult breast cancers manifesting as axillary lymph node metastasis in men. They had a palpable lesion on axillary area several years ago and had not seen a doctor about it. As such there was no abnormality on evaluations for cancer except for axillary lymph node showing signs of carcinoma (primary or metastatic) on biopsy and estrogen receptor-positive and progesterone receptor-positive on immunohistochemistry. The patients were diagnosed with occult breast cancer, and treatments were performed. Herein, we report the rare cases of occult breast cancers in men.

Keap1 is a cytoplasmic repressor of the transcription factor Nrf2, and its degradation induces Nrf2 activation, leading to upregulation of antioxidant phase II genes. We investigated the roles of phase II genes in vascular inflammation and septic injury using Keap1 siRNA and elucidated its underlying mechanism. Selective knockdown of Keap1 with siRNA promoted Nrf2-dependent expression of phase II genes in endothelial cells, such as heme oxygenase-1 (HO-1), glutamate-cysteine ligase (GCL), and peroxiredoxin-1 (Prx1), resulting in the elevation of cellular glutathione levels and suppression of tumor necrosis factor (TNF)-α-induced intracellular H(2)O(2) accumulation. Keap1 knockdown inhibited TNF-α-induced expression of intracellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) by suppressing NF-κB activation via inhibition of its upstream modulators, Akt, NIK, and IKK, resulting in the elevation of monocyte adhesion to endothelial cells. Importantly, these events were reversed by HO-1 and GCL inhibitors and Prx1-specific siRNA. Keap1 knockdown also inhibited endotoxin-induced expression of inducible nitric oxide synthase (iNOS) and TNF-α by upregulating HO-1, GCL, and Prx1 expression in macrophages. Moreover, in vivo Keap1 knockdown increased the expression of phase II genes and suppressed the expression of ICAM-1, VCAM-1, iNOS, and TNF-α in an endotoxemic mouse model, resulting in significant protection against liver and lung injuries and lethality. Our results indicate that Keap1 knockdown prevents NF-κB-mediated vascular inflammation and endotoxic shock by suppressing NF-κB-mediated inflammatory gene expression via upregulation of Nrf2-mediated antioxidant genes. Thus, siRNA targeting Keap1 may provide a new therapeutic approach for inflammation-associated vascular diseases and sepsis.

Purpose Internal mammary lymph node (IMLN) metastasis is an important prognostic indicator in breast cancer. However, the necessity of internal mammary sentinel lymph node biopsy for accurate staging, for choosing adjuvant treatment, and as a prognostic indicator, has remained controversial. Methods From January 2001 to December 2006, 525 female breast cancer patients underwent radical surgery after preoperative lymphatic scintigraphy. We retrospectively analyzed the follow-up results, recurrences, and deaths of all patients. Results There was no significant difference in the clinicopathological characteristics between the axilla and the IMLN groups. The median follow-up period was 118.8 months (range, 7-122 months) in the axilla group and 107.7 months (range, 14-108 months) in the IMLN group. During the median follow-up period, the breast cancer-related death rate in the axilla group was 3.6%, which was not significantly different from that of the IMLN group (1.3%) (p=0.484). The five-year survival rates did not differ between the two groups (p=0.306). The overall recurrence rate and the locoregional recurrence rate also did not differ between the two groups (p=0.835 and p=0.582, respectively). The recurrence rate of IMLN (both ipsilateral and contralateral) metastasis was very low, accounting for 0.5% in the axilla group and 1.3% in the IMLN group (p=0.416). Conclusion The long-term follow-up results showed that there was no significant difference in both overall outcome and regional recurrence between the two groups. Therefore, the requirement for identification of nodal basins outside the axilla or IMLN sentinel biopsy should be reconsidered.

Ginseng berry possesses higher ginsenoside content than its root, which has been traditionally used in herbal medicine for many human diseases, including atherosclerosis. We here examined the antiatherogenic effects of the Korean ginseng berry extract (KGBE) and investigated its underlying mechanism of actionin vitroandin vivo. Administration of KGBE decreased atherosclerotic lesions, which was inversely correlated with the expression levels of phase II genes to include heme oxygenase-1 (HO-1) and glutamine-cysteine ligase (GCL). Furthermore, KGBE administration suppressed NF-κB-mediated expression of atherogenic inflammatory genes (TNF-α, IL-1β, iNOS, COX-2, ICAM-1, and VCAM-1), without altering serum cholesterol levels, in ApoE-/-mice fed a high fat-diet. Treatment with KGBE increased phase II gene expression and suppressed lipopolysaccharide-induced reactive oxygen species production, NF-κB activation, and inflammatory gene expression in primary macrophages. Importantly, these cellular events were blocked by selective inhibitors of HO-1 and GCL. In addition, these inhibitors reversed the suppressive effect of KGBE on TNF-α-mediated induction of ICAM-1 and VCAM-1, resulting in decreased interaction between endothelial cells and monocytes. These results suggest that KGBE ameliorates atherosclerosis by inhibiting NF-κB-mediated expression of atherogenic genes via upregulation of phase II enzymes and thus has therapeutic or preventive potential for atherosclerosis.

article i nfo Taurine, a non essential sulfur-containing amino acid, plays a critical role in cardiovascular functions. We here examined the effect of taurine on angiogenesis and its underlying signal pathway. Taurine treatment in- creased angiogenesis in vitro and in vivo, which was followed by activation of the phosphatidylinositol 3- kinase (PI3K)/Akt, MEK/ERK, and Src/FAK signaling pathways. Further, taurine promoted endothelial cell cycle progression to the S and G2/M phases by up-regulating the positive cell cycle proteins, particularly cyclins D1 and B, as well as down-regulating the negative cell cycle proteins, p53 and p21 WAF1/CIP1 , resulting in Rb phosphorylation. This angiogenic event was inhibited by inhibitors of PI3K and MEK. In addition, a PI3K inhibitor blocked the activation of Akt and ERK, while Akt knockdown did not affect taurine-induced ERK ac- tivation, indicating that PI3K is an upstream mediator of both MEK and Akt. Taurine-induced endothelial cell migration was suppressed by Src inhibitor, but not by other inhibitors, suggesting that the increase in cell mi- gration is regulated by Src-dependent pathway. Moreover, inhibition of cellular taurine uptake by β-alanine and taurine transporter knockdown promoted taurine-induced cell proliferation, ERK and Akt activation, and in vivo angiogenesis, suggesting that extracellular taurine induces angiogenesis. However, taurine did not in- duce vascular inflammation and permeability in vitro and in vivo. These data demonstrate that extracellular taurine promotes angiogenesis by Akt- and ERK-dependent cell cycle progression and Src/FAK-mediated cell migration without inducing vascular inflammation, indicating that it is potential use for the treatment of vascular dysfunction-associated human diseases.

Although it has been suggested that smad7 blocks downstream signaling of TGF-β, the role of smad7 in the EGF signaling pathway has not been fully elucidated. We determined the effect of smad7 on EGF-induced MMP-9 expression in SKBR3 breast cancer cells. The expression of smad7 and MMP-9 was increased by EGF or TGF-β1, respectively, and further increased by EGF and TGF-β1 co-treatment. EGF induced the phosphorylation of EGFR, smad3, ERK, and JNK, and MMP-9 expression was decreased by the EGFR inhibitor, AG1478. In addition, EGF-induced MMP-9 expression was inhibited by UO126 (a MEK1/2 inhibitor) or SIS3 (a smad3 inhibitor), but not by SP600125 (a JNK inhibitor). Interestingly, EGF-induced smad3 phosphorylation was completely blocked by smad7 over-expression, but not the phosphorylation of ERK and JNK. EGF- or TGF-β1-induced MMP-9 expression was completely decreased by adenoviral-smad7 (Ad-smad7) over-expression. We also investigated the role of smad3 on EGF-induced MMP-9 expression and showed that EGF-induced MMP-9 expression was decreased by smad3 siRNA transfection, whereas EGF-induced MMP-9 expression was further increased by smad3 over-expression, as expected. This study showed that EGF-induced smad3 phosphorylation mediates the induction of MMP-9, whereas smad7 inhibits TGF-β1 as well as the EGF signaling pathway in SKBR3 cells.

Angiosarcoma of the breast is rare. The purpose of the present study was to evaluate the clinicopathologic characteristics and the clinical outcomes of patients with primary breast angiosarcoma.We analyzed the clinicopathologic factors of patients with angiosarcoma of the breast treated between 1997 and 2010 at the Samsung Medical Center. We reviewed the related demographic data, preoperative imaging studies, method of histologic confirmation, tumor size, histologic grades, status of hormonal receptors, treatment modality, and survival data.Nine women with angiosarcoma of the breast were identified. The median age of patients with primary angiosarcoma of the breast at diagnosis was 31 years (range: 19-63 years), and the median tumor size was 9.0 cm (range: 3.5-10.7 cm). Seven patients (77.7%) died within a median follow-up of 46.7 months (range: 3.9-63.3 months), and all deaths were directly attributed to angiosarcoma. Overall, the median time from diagnosis of angiosarcoma to death was 46.8 months (range: 8.21-63.3 months). The 5 year overall survival with angiosarcoma was 42.9%.Primary angiosarcoma of the breast is a rare malignancy with a poor prognosis, even with complete resection. Chemotherapy and radiation therapy have limited value as treatments to date. Total mastectomy appears to be the most appropriate and beneficial treatment. More aggressive surgical management should be considered, and future clinical research should explore the most appropriate adjuvant therapy in the treatment of angiosarcoma.

Papillary thyroid cancer (PTC) is the most common differentiated thyroid carcinoma. Metastases usually occur in regional lymph nodes or to lungs. Distant metastases to skeletal muscle are rare. Here, we report a patient with a solitary metastasis to skeletal muscle.A 31-year-old woman was found on routine physical examination to have a 1-cm nodule in the right thyroid lobe. The patient underwent endoscopic total thyroidectomy with central cervical lymph node dissection in April 2008. Pathological analysis showed a 1.5 × 0.9 cm PTC in the right thyroid lobe with extension into perithyroidal soft tissue and lymph node involvement (all six central lymph nodes examined were positive). After surgery, she received 100 mCi of radioactive iodine. Subsequently, the patient was found to have a lateral neck recurrence and, therefore, underwent right unilateral modified radical neck dissection followed by additional radioactive iodine ablation. In February 2010, her serum thyroglobulin was 19.4 ng/mL, but the neck ultrasound was negative. However, a fluorodeoxyglucose (FDG) positron emission tomography scan showed focal FDG uptake in the vastus medialis muscle of the right distal femur. A 0.9 × 0.5 cm, well-defined, whitish mass in the vastus medialis muscle was confirmed on histopathology to be metastatic PTC.Here, we report an adult woman who presented with a thyroid nodule that was noted to be PTC on histopathology after total thyroidectomy. Almost 2 years later, she was noted to have had focal FDG uptake consistent in the region of the right femur. A solitary metastasis of PTC in the right vastus medialis muscle was resected. A MEDLINE (Medical Literature Analysis and Retrieval System Online) search showed that this is only the third report of PTC with a distant, solitary skeletal muscle metastasis.Distant skeletal metastasis in PTC is very rare. Until the availability of FDG to detect skeletal metastasis of PTC, they may have been more difficult to discern.

Cyclooxygenase-2 (COX-2) has been reported to be elevated in many cancers, including breast and colorectal cancers, resulting in accumulation of prostaglandin E2 in the cancer cell environment. In this study, we investigated the effect of pifithrin (PFT)-α, an inhibitor of p53 transactivation, on COX-2 expression in breast and fibrosarcoma cells. Our results showed that COX-2 expression was dose-dependently increased by PFT-α in MDA-MB231 breast cancer cells with mutant p53. In addition, the expression level of COX-2 was also increased by PFT-α in normal fibroblasts as well as in HT1080 fibrosarcoma cells with p53 wild-type cells. To verify the regulatory mechanism of COX-2 in response to PFT-α, we pretreated cells with a mitogen-activated protein kinase (MAPK) kinase (MEK)1/2 inhibitor (UO126) and a phosphoinositide-3 (PI-3K) inhibitor (LY294002). PFT-α-induced COX-2 expression was significantly decreased by UO126 and LY294002 in MDA-MB231 cells. However, the phosphorylation of extracellular signal-regulated kinase (ERK) was increased by PFT-α, but not Akt phosphorylation. Finally, we confirmed the correlation of the MEK and PI-3K pathway and COX-2 expression using the constitutively active (CA)-MEK and myr-Akt adenovirus systems. COX-2 expression was increased by CA-MEK transfection, but not by myr-Akt. Taken together, we have demonstrated that PFT-α-induced COX-2 expression is regulated through a MEK/ERK pathway in MDA-MB231 human breast cancer cells.

Purpose: To present the author’s experience with various treatment methods of granulomatous lobular mastitis (GLM) and to determine effective treatment methods of GLM. Methods: Fifty patients who were diagnosed with GLM were classified into five groups based on the initial treatment methods they underwent, which included observation (n = 8), antibiotics (n = 3), steroid (n = 13), drainage (n = 14), and surgical excision (n = 12). The treatment processes in each group were examined and their clinical characteristics, treatment processes, and results were analyzed respectively. Results: Success rates with each initial treatment were observation, 87.5%; antibiotics, 33.3%; steroids, 30.8%; drainage, 28.6%; and surgical excision, 91.7%. In most cases of observation, the lesions were small and the symptoms were mild. A total of 23 patients underwent surgical excision during treatment. Surgical excision showed particularly fast recovery, high success rate (90.3%) and low recurrence rate (8.7%). Conclusion: The clinical course of GLM is complex and the outcome of each treatment type are variable. Surgery may play an important role when a lesion is determined to be mass-forming or appears localized as an abscess pocket during breast examination or imaging study.

Purpose We conducted this study to study the clinical correlation between the characteristics of gastric cancer and serum selenium and zinc levels. Materials and methods The following data were measured in the baseline serum selenium and zinc levels of 74 patients with curative gastrectomy subsequent to confirmed gastric cancer, from March 2005 to August 2012. Results Among the 74 gastric cancer patients, 53 patients were male. Mean serum selenium and zinc levels were 118.7±33.1 ug/L and 72.2±24.3 ug/dl, respectively. Seven patients (9.5%) showed lower selenium level, and 33 patients (44.6%) showed lower zinc level. Serum Selenium level was 99.1±31.8 ug/L in cardia cancer group (10 cases) and 121.8±32.4 ug/L in non-cardia cancer group (64 cases)(P=0.044). According to tumor gross type, zinc level was 78.7±29.6 ug/dl in early gastric cancer (33) and 66.9±17.8 ug/dl in advanced gastric cancer (41) (P=0.064). Conclusions The serum selenium level was highly correlated with the location of gastric cancer. The serum zinc level was lower in advanced gastric cancer.

Purpose: We analyzed the responses of patients with locally advanced breast cancer to neoadjuvant chemotherapy (NAC) and NAC combined with neoadjuvant human epidermal growth factor receptor-2 (HER2) targeted therapy (NCHTT). Methods: We retrospectively reviewed 59 patients with HER2 amplified locally advanced breast cancer among patients who were treated surgically after neoadjuvant therapy at Samsung Medical Center between 2005 and 2009. Thirty-one patients received conventional NAC and 28 patients received NCHTT. Pathologic responses were assessed according to response evaluation criteria in solid tumors (RECIST) guidelines. Results: Pathologic complete response (pCR) was achieved in 13 out of 28 patients treated with NCHTT and in 6 out of 31 patients treated with NAC alone (46.4% vs. 19.4%, respectively, P = 0.049). Breast conserving surgery (BCS) was more frequently performed in the NCHTT group than in the NAC only group (71.4% vs. 19.4%, P ＜ 0.001). The 3-year recurrence-free survival (RFS) rate was 100% in the NCHTT group and 76.4% in the NAC group (P = 0.014). Together, NCHTT, type of operation (BCS vs. mastectomy) and pathologic nodal status were significant prognostic factors for RFS in univariate analysis. Conclusion: We found that NCHTT produced higher pCR rates than NAC alone in locally advanced breast cancer.