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Background: Patients achieving pathological complete response (pCR) post-neoadjuvant chemoradiotherapy (nCRT) and surgery for locally advanced esophageal squamous cell carcinoma (ESCC) have a favorable prognosis. However, recurrence occurs in approximately 20-30% of all patients, with few studies evaluating their prognostic factors. We identified these prognostic factors, including inflammation-based markers, in patients with ESCC showing pCR after nCRT and surgery., Patients and Methods: Patients with ESCC undergoing esophagectomy post-nCRT (January 2007-August 2017) were studied. Survival analysis evaluated 5-year overall (OS) and recurrence-free survival (RFS). Risk factors, including inflammation factors, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio (PLR), were analyzed using Cox-proportional hazards model., Results: Overall, 123patients participated herein. After a median follow-up duration of 67 months (44-86 months), 17 patients (12.3%) had recurrent disease. The 5-year OS and RFS rates were 71.6% and 68.0%, respectively. In the multivariable analysis, older age ( ≥ 60 years) [hazard ratio (HR) 3.228, 95% confidence interval (CI) 1.478-7.048, p = 0.003], higher pretreatment T stage (≥ T3; HR 2.563, 95% CI 1.335-4.922, p = 0.005), nonapplication of induction chemotherapy (HR 2.389, 95% CI 1.184-4.824, p = 0.015), and higher post-nCRT PLR (≥ 184.2; HR 2.896, 95% CI 1.547-5.420, p = 0.001) were poor independent prognostic factors for 5-year RFS. The patient group with three to four identified factors with poor outcomes exhibited a 5-year RFS rate of 46.2%., Conclusions: Significant prognostic factors include higher post-nCRT PLR, older age, higher clinical T stage, and nonapplication of induction chemotherapy. Identifying higher recurrence risk patients is crucial for tailored follow-up and treatment., (© 2024. Society of Surgical Oncology.)

Background: Effective treatment for patients with advanced thyroid cancer is lacking. Metabolism reprogramming is required for cancer to undergo oncogenic transformation and rapid tumorigenic growth. Glutamine is frequently used by cancer cells for active bioenergetic and biosynthetic needs. This study aims to investigate whether targeting glutamine metabolism is a promising therapeutic strategy for thyroid cancer., Methods: The expression of glutaminase (GLS) and glutamate dehydrogenase (GDH) in thyroid cancer tissues was evaluated by immunohistochemistry, and glutamine metabolism-related genes were assessed using real time-qPCR and western blotting. The effects of glutamine metabolism inhibitor 6-diazo-5-oxo-l-norleucine (DON) on thyroid cancer cells were determined by CCK-8, clone formation assay, Edu incorporation assay, flow cytometry, and Transwell assay. The mechanistic study was performed by real time-qPCR, western blotting, Seahorse assay, and gas chromatography-mass spectrometer assay. The effect of DON prodrug (JHU-083) on thyroid cancer in vivo was assessed using xenograft tumor models in BALB/c nude mice., Results: GLS and GDH were over-expressed in thyroid cancer tissues, and GLS expression was positively associated with lymph-node metastasis and TNM stage. The growth of thyroid cancer cells was significantly inhibited when cultured in glutamine-free medium. Targeting glutamine metabolism with DON inhibited the proliferation of thyroid cancer cells. DON treatment did not promote apoptosis, but increased the proportion of cells in the S phase, accompanied by the decreased expression of cyclin-dependent kinase 2 and cyclin A. DON treatment also significantly inhibited the migration and invasion of thyroid cancer cells by reducing the expression of N-cadherin, Vimentin, matrix metalloproteinase-2, and matrix metalloproteinase-9. Non-essential amino acids, including proline, alanine, aspartate, asparagine, and glycine, were reduced in thyroid cancer cells treated with DON, which could explain the decrease of proteins involved in migration, invasion, and cell cycle. The efficacy and safety of DON prodrug (JHU-083) for thyroid cancer treatment were verified in a mouse model. In addition to suppressing the proliferation and metastasis potential of thyroid cancer in vivo, enhanced innate immune response was also observed in JHU-083-treated xenograft tumors as a result of decreased expression of cluster of differentiation 47 and programmed cell death ligand 1., Conclusions: Thyroid cancer exhibited enhanced glutamine metabolism, as evidenced by the glutamine dependence of thyroid cancer cells and high expression of multiple glutamine metabolism-related genes. Targeting glutamine metabolism with DON prodrug could be a promising therapeutic option for advanced thyroid cancer., (© 2024. The Author(s).)

Background: Postendoscopic submucosal dissection electrocoagulation syndrome (PEECS) is commonly observed after performing endoscopic submucosal dissection (ESD) for esophageal neoplasia. However, data on the incidence and risk factors for PEECS in the esophagus are lacking due to an unclear definition of PEECS and varied clinical settings. Therefore, we aimed to determine the risk factors for PEECS in patients undergoing ESD for esophageal neoplasia., Methods: We retrospectively reviewed data of relevant clinical and endoscopy-specific parameters from 202 consecutive patients with esophageal neoplasias (139 carcinomas and 63 dysplasias) who underwent ESD under general anesthesia. Esophageal PEECS was defined by satisfying at least two of the following criteria: fever ≥ 37.8 °C, leukocytosis ≥ 10,800/mm 3 , and localized chest pain ≥ 5/10 points as assessed on a numeric rating scale within 24 h after ESD. Significant factors associated with PEECS were determined by regression analysis., Results: PEECS was recorded in 98 of 202 (48.5%) patients. Patients with PEECS exhibited a larger tumor size (25.0 vs. 17.0 mm, P = 0.002), longer procedure (40.0 vs. 29.5 min, P = 0.021) and hemostasis times (5.0 vs. 3.5 min, P = 0.004), required greater submucosal injection volume (60.0 mL vs. 50.0 mL, P = 0.030), and had a lower rate of local steroid injection (4.1% vs. 12.5%, P = 0.029) than those without PEECS. Multivariate regression analysis revealed tumor size ≥ 17 mm (P = 0.047), procedure time ≥ 33 min (P = 0.027), and hemostasis time ≥ 5 min (P = 0.007) as risk factors for PEECS. In addition, local steroid injection was a significant negatively associated factor (P = 0.001)., Conclusions: Patients with a large tumor, prolonged procedure and hemostasis times are at a high risk of PEECS occurrence. Further, local steroid injection is a negatively associated factor., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Most gastric leiomyomas are asymptomatic and benign subepithelial tumors (SETs); however, some may increase in size or become symptomatic. Understanding their natural history is therefore important to their management. We investigated the natural history of histologically proven gastric leiomyomas., Methods: We retrospectively reviewed histologically proven gastric leiomyoma cases at a tertiary center. The baseline characteristics of these cases were analyzed, and those with a follow-up period of at least 12 months without immediate resection were evaluated. The primary outcome was the frequency of size increase of more than 25% during the follow-up period, and the secondary outcome was the histopathologic results in cases that underwent resection., Results: Among the 231 patients with histologically proven gastric leiomyomas, the most frequent location was the cardia (77.1%), and the median size was 3 cm (IQR 2-4 cm). Eighty-four cases were followed up over a median period of 50.8 months (IQR 27.2-91.3 months). During the follow-up period, tumor size increased in two cases (2.4%). Surgical results showed that one case was leiomyoma, and the other was leiomyosarcoma. Among the remaining cases without change in size, 15 underwent surgical resection (n = 10) or endoscopic resection (n = 5), and all cases were confirmed as leiomyoma., Conclusions: Most gastric leiomyomas are benign SETs, and an increase in size is not frequent, even in large-sized cases. Close monitoring with routine follow-up without resection may be sufficient in cases of histologically proven gastric leiomyoma. However, in cases of ulceration or size increase, resection may be beneficial., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: The increased use of proton pump inhibitors (PPIs) in the elderly has raised concerns about potential severe adverse effects. Our systematic review investigated the mortality associated with PPI use in elderly populations., Methods: We searched MEDLINE, EMBASE, and the Cochrane Library for relevant publications until August 2022. We included randomized controlled trials (RCTs), quasi-RCTs, and observational studies on the association between proton pump inhibitors and mortality in the elderly. To estimate the pooled relative risk (RR) and 95% confidence interval (CI), the inverse-variance random effect model was used. Heterogeneity was assessed using the I 2 test. Subgroup analyses were performed by follow-up period, population, and study design., Results: A total of 4 RCTs and 36 cohort studies were included in the meta-analysis. Four RCTs showed that there was no significant association between PPIs and the risk of death. From 23 observational studies (26 cohorts), the use of proton pump inhibitors was not significantly associated with increased mortality in the elderly (RR 1.14; 95% CI, 0.90-1.45). However, when controlling for covariates from 33 observational studies (41 cohorts), proton pump inhibitors in older adults aged 50 years or more were significantly associated with a 15% higher risk of mortality compared to nonusers (RR 1.15; 95% CI, 1.10-1.20)., Conclusions: Our meta-analysis of RCTs found that PPIs did not show a significant association with increased mortality risk in older adults. However, the meta-analysis of cohort studies and long-term follow-up studies showed a higher increased risk of death with PPI use in older adults. The prescription of PPIs in patients aged 50 years or older should be carefully considered., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The likelihood of recurrence of gastric hyperplastic polyps (GHPs) following endoscopic resection and the need for long-term follow-up remain unknown. We, therefore, aimed to investigate the factors associated with the recurrence and cumulative incidence of GHPs over a 10-year period., Methods: Between May 1995 and December 2020, 1,018 GHPs > 1 cm were endoscopically resected from 869 patients. Medical records of these patients were retrospectively reviewed and their clinical features and outcomes were assessed. Groups of GHPs with recurrence and those without recurrence group were compared, and univariate and multivariable analyses were performed to identify the potential risk factors for GHP recurrence., Results: A total of 104 (12.0%) patients who underwent endoscopic removal of GHPs experienced recurrence. Compared to patients without recurrent GHPs, those with recurrent GHPs showed considerably larger median polyp size (28 mm vs. 14 mm, P < 0.001), a higher proportion of multiple polyps (41.3% vs. 29.3%, P = 0.020), polyps with lobulation (63.5% vs. 40.3%, P = 0.001), and exudate (63.5% vs. 46.8%, P = 0.001). Compared to the local recurrence (n = 52) group, the metachronous recurrence (n = 52) group had larger median polyp size (20 mm vs. 16 mm, P = 0.006) as well as higher rates of polyp lobulation (86.5% vs. 40.4%, P < 0.001) and exudate (82.7% vs. 44.4%, P = 0.001). After primary GHP excision, the cumulative incidence of recurrence was 7.2%, 12.7%, and 19.6% at 2 years, 5 years, and 10 years, respectively., Conclusion: The incidence of GHP recurrence following endoscopic excision increased as the follow-up period increased, especially in patients whose GHPs were large-sized, multiple, or characterized by surface exudates/lobulations., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Endoscopic submucosal dissection (ESD) is sometimes performed for early gastric cancer (EGC) which is not indicated for endoscopic resection (ER) in elderly patients considering old age and comorbidities. We aimed to compare outcomes between ESD and surgery in elderly patients with EGC that is not indicated for ER., Methods: Elderly patients aged ≥ 75 years who underwent either ESD or surgery for EGC which was not indicated for ER between 2005 and 2015 were retrospectively investigated., Results: Among a total of 294 patients, 59 (20.1%) and 235 (79.9%) patients underwent ESD and surgery as the initial treatment, respectively. The ESD group had smaller size of tumors (25 vs. 30 mm, p = .001) and higher rate of differentiated-type cancer than the surgery group had (88.1% vs. 60.9%, p = 0.001). With a median observation period of 91.8 months (range 11.6-198.1 months), 141 (48.0%) patients died: 25 (42.4%) and 116 (49.4%) patients in the ESD group and the surgery group, respectively. Overall survival and disease-free survival between the two groups had no significant differences (p = 0.982. p = 0.155, respectively)., Conclusions: ESD may be an alternative option for EGC which is not indicated for ER in elderly patients aged ≥ 75 years, considering old age and comorbidity., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background and Aims: As the incidence of duodenal neuroendocrine tumors (DNET) is steadily increasing, the role of endoscopic treatment for appropriate lesions is becoming more significant. We aimed to compare the outcomes according to lesion size and endoscopic mucosal resection (EMR) techniques for DNET treatment., Patients and Methods: Patients who underwent endoscopic treatment for DNET between June 2000 and December 2019 were included. The clinicopathologic features and treatment outcomes were investigated by reviewing medical records., Results: Overall, 104 cases underwent endoscopic resection for nonampullary DNET, including conventional EMR (n = 57), cap-assisted EMR (EMR-C, n = 19), and precut EMR (EMR-P, n = 28). The en bloc resection rates (100% vs. 94.7% vs. 96.4%) and histologic complete resection rates (45.6% vs. 52.6% vs. 57.1%) were not significantly different between the EMR, EMR-C, and EMR-P groups. The histologic complete resection rates were significantly higher in lesions < 10 mm than in lesions ≥ 10 mm (69.8% vs. 38.9%, P = 0.013). In lesions < 10 mm, perforation occurred more frequently in the modified EMR group than in the conventional EMR group (13.2% vs. 0.0%, P = 0.007). During the median follow-up period of 88.0 months, the recurrence-free survival (92.2% vs. 94.4% vs. 92.1%) and overall survival (98.0% vs. 88.1% vs. 100.0%) rates did not show significant differences between the EMR, EMR-C, and EMR-P groups., Conclusion: Conventional EMR and modified EMR are feasible and effective for the treatment of nonampullary DNET sized < 10 mm and limited to mucosal and submucosal layer. Additionally, endoscopists should be aware of the high risk of perforation in modified EMR., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Marginal ulcer bleeding (MUB) is a complication that can occur following several types of surgery. However, few studies exist on it. Therefore, this study aimed to compare the clinical outcomes of MUB with those of peptic ulcer bleeding (PUB)., Methods: Between January 2013 and December 2017, 5,076 patients underwent emergent esophagogastroduodenoscopy for suspected upper gastrointestinal bleeding. We retrospectively reviewed and analyzed the medical records of MUB and PUB patients and developed a propensity score matching (PSM) method to adjust for between-group differences in baseline characteristics with 1:2 ratios. Sex, age, body mass index (BMI), underlying diseases, and drugs were included as matching factors., Results: A total of 64 and 678 patients were diagnosed with MUB and PUB, respectively, on emergent esophagogastroduodenoscopy, and 62 and 124 patients with MUB and PUB, respectively, were selected after PSM. Rebleeding was significantly higher in patients with MUB than in those with PUB (57.8% vs 9.1%, p < 0.001). Mortality caused by bleeding was higher in patients with MUB than in those with PUB (4.7% vs. 0.4%, p < 0.001). Multivariate analysis revealed that proton pump inhibitor (PPI) administration (odds ratio [OR], 0.14; 95% confidence interval [CI], 0.03-0.56; p = 0.011) after first bleeding was inversely correlated with MUB rebleeding. Large ulcer size (> 1 cm) (OR, 6.69; 95% CI, 1.95-27.94; p = 0.005) and surgery covering pancreas (OR, 3.97; 95% CI, 1.19-15.04) were independent risk factors for MUB rebleeding., Conclusions: MUB showed a severe clinical course than PUB. Therefore, MUB should be managed more cautiously, especially for large ulcers and pancreatic surgery. Prophylactic PPI administration may be helpful in reducing rebleeding in MUB., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Subepithelial tumor (SET) size is important in determining the treatment plan; however, size estimation for gastric SETs has not been well investigated. We aimed to investigate which method predicts SET size most accurately by retrospectively analyzing surgically removed SETs., Methods: From January 2015 through June 2020, patients who underwent surgical gastric SET removal at Asan Medical Center, Seoul, Korea, were enrolled. SET sizes measured by pathologists and endoscopists were retrospectively reviewed. The reliability of SET size measurement by endoscopic ultrasonography (EUS) and endoscopy was calculated using intraclass correlation coefficient (ICC), with pathologic size as the gold standard., Results: Overall, EUS was highly reliable (ICC 0.86, P < 0.001), and endoscopy was moderately reliable (ICC 0.75, P < 0.001). When analyzed according to SET location, endoscopy was highly reliable in the lesser curvature's lower third (ICC 0.86, P = 0.014), middle third (ICC 0.88, P < 0.001), and upper third (ICC 0.90, P < 0.001); as well as the anterior wall's middle third (0.84, P < 0.001) and the posterior wall's upper third (ICC 0.80, P < 0.001). EUS (ICC 0.96, P = 0.005) and endoscopy (ICC 0.95, P = 0.008) both were most reliable for lower-third posterior wall lesions, whereas endoscopy was unreliable for middle-third greater curvature lesions (ICC 0.41, P = 0.05)., Conclusions: Both EUS and endoscopy were reliable methods for measuring gastric SET size, and overall, EUS was more reliable than endoscopy. In terms of SET location, EUS was consistently reliable, whereas endoscopy showed variable reliability. When measuring SET size by endoscopy, additional size measurements with EUS should be considered in certain locations., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Although upper gastrointestinal (GI) neoplasms are not rare in patients with familial adenomatous polyposis (FAP), few studies have focused on them and the long-term outcomes of their treatment by endoscopy. Therefore, we aimed to investigate the prevalence and endoscopic treatment outcomes of upper GI neoplasms in patients with FAP., Methods: Among 215 patients diagnosed with FAP between January 1991 and December 2019, 208 who underwent esophagogastroduodenoscopy were eligible. The clinical features and endoscopic treatment outcomes of upper GI neoplasms were retrospectively investigated and analyzed., Results: Among the enrolled patients, 113 (54.3%) had one or more upper GI neoplasms: gastric adenoma (n = 34), gastric cancer (n = 7), nonampullary duodenal adenoma (n = 86), and ampullary adenoma (n = 53). Among patients with gastric neoplasms (n = 37), 24 (64.9%) underwent treatment (endoscopic treatment: 22, surgery: 2). No tumor-related mortality occurred during median follow-up of 106 months (interquartile range [IQR] 63-174). Endoscopic treatment was performed in 47 (54.7%) of 86 patients with nonampullary duodenal adenoma and in 32 (60.4%) of 53 patients with ampullary adenoma. No patient underwent surgery for duodenal neoplasms, and no tumor-related mortality occurred during median follow-up of 88 months (IQR 42-145). The proportion of patients with increased Spigelman stage at 2 years after the initial diagnosis or treatment was significantly higher in untreated group than in the group treated for duodenal neoplasms (27.3% vs. 0.0%, p = 0.001)., Conclusion: Endoscopic surveillance in FAP patients is important for the detection and treatment of upper GI neoplasms in early stage. In particular, endoscopic therapy for duodenal neoplasms can reduce the severity of duodenal polyposis., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Although the rate of early detection and endoscopic treatment of gastric neuroendocrine tumors (NETs) is steadily increasing, there are insufficient studies on the long-term outcomes of endoscopic treatment. Therefore, we aimed to investigate the clinical features and long-term outcomes of endoscopic treatment for type 1 gastric NETs., Methods: Subjects who underwent endoscopic treatment for gastric NETs between March 1997 and December 2015 were included. Clinical features and endoscopic treatment outcomes were retrospectively investigated by reviewing medical records., Results: In total, 125 subjects underwent endoscopic treatment including forceps biopsy (n = 21), argon plasma coagulation (n = 1), endoscopic mucosal resection (EMR, n = 62), and endoscopic submucosal dissection (ESD, n = 41). In total, 103 patients with 114 lesions, who underwent EMR or ESD, were analyzed to evaluate endoscopic and oncologic outcomes. The rates of en bloc resection in the EMR and ESD groups were 91.5% and 97.7%, respectively. Complete resection rates were significantly higher in the ESD group than in the EMR group; it was also higher in < 1-cm small-sized lesions than in 1-2-cm large-sized lesions. Adverse events were similar between the two groups. During a median follow-up period of 63 months, local recurrence rates were 6.5% and 2.4% in the EMR and ESD groups, respectively, and the disease-free survival rate did not differ significantly between the groups., Conclusion: Endoscopic treatment for type 1 gastric NETs less than 2 cm in diameter and confined to mucosal and submucosal layers could be an effective and safe treatment strategy based on the favorable long-term outcome., (© 2021. The Society for Surgery of the Alimentary Tract.)

Reactive oxygen species (ROS) exacerbate stroke-induced cell damage. We found that ShcA, a protein that regulates ROS, is highly expressed in a Rose Bengal photothrombosis model. We investigated whether ShcA is essential for mitophagy in ROS-induced cellular damage and determined whether ROS exacerbate mitochondrial dysfunction via ShcA protein expression. Ischemic stroke was generated by Rose Bengal photothrombosis in mice. To silence ShcA protein expression in the mouse brain, ShcA-targeting siRNA-encapsulated nanoparticles were intrathecally injected into the cisterna magna. Upon staining with antibodies against ShcA counterpart caspase-3 or NeuN, we found that the ShcA protein expression was increased in apoptotic neurons. In addition, mitochondrial dysfunction and excessive mitophagy were evident in photothrombotic stroke tissue. Infarct volumes were significantly reduced, and neurological deficits were diminished in the ShcA siRNA nanoparticle-treated group, compared with the negative control siRNA nanoparticle-treated group. We confirmed that the reduction of ShcA expression by nanoparticle treatment rescued the expression of genes, associated with mitochondrial dynamics and mitophagy mediation in a stroke model. This study suggests that the regulation of ShcA protein expression can be a therapeutic target for reducing brain damage with mitochondrial dysfunction caused by thrombotic infarction., (© 2020. Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Benign esophageal anastomotic strictures have typically been treated using endoscopic methods, often with balloon dilatation (BD). However, recurrent esophageal strictures after BD have been reported. We evaluated the efficacy and safety of endoscopic incisional therapy (EIT) and BD for treating an anastomotic stricture after a total gastrectomy., Methods: Subjects who underwent EIT or BD as a first treatment for esophagojejunostomy anastomotic stricture after a total gastrectomy between January 2010 and December 2018 were eligible. The medical records of these cases were retrospectively reviewed. Stricture was defined as an inability to pass a normal diameter endoscope (10.2 mm). The stricture area was incised under direct vision with the nano-insulated-tip knife in a radial fashion parallel to the longitudinal axis of the esophagus., Results: Twenty-one patients in our database presented with benign anastomotic stricture after a total gastrectomy for advanced gastric cancer. The BD group included 12 patients. The remaining nine patients underwent EIT, and three of these cases received an immediate additional BD. The re-stricture rate was significantly different between the BD and EIT groups (41.7% vs. 0%, respectively; P = 0.045). There were no significant differences in procedure time, interval from surgery to first stricture, hospitalization period, or complication rates between the groups. One patient developed a microperforation during BD and was treated without surgical intervention., Conclusions: EIT is a safe and effective primary treatment modality compared with BD for esophagojejunostomy anastomotic stricture after a total gastrectomy as it shows a significantly lower re-stricture rate., (© 2020. The Society for Surgery of the Alimentary Tract.)

Monoamine oxidase-B (MAO-B) is a well-established therapeutic target for Parkinson's disease (PD); however, previous clinical studies on currently available irreversible MAO-B inhibitors have yielded disappointing neuroprotective effects. Here, we tested the therapeutic potential of KDS2010, a recently synthesized potent, selective, and reversible MAO-B inhibitor in multiple animal models of PD. We designed and synthesized a series of α-aminoamide derivatives and found that derivative KDS2010 exhibited the highest potency, specificity, reversibility, and bioavailability (> 100%). In addition, KDS2010 demonstrated significant neuroprotective and anti-neuroinflammatory efficacy against nigrostriatal pathway destruction in the mouse MPTP model of parkinsonism. Treatment with KDS2010 also alleviated parkinsonian motor dysfunction in 6-hydroxydopamine-induced and A53T mutant α-synuclein overexpression rat models of PD. Moreover, KDS2010 showed virtually no toxicity or side effects in non-human primates. KDS2010 could be a next-generation therapeutic candidate for PD., (© 2021. The Author(s).)

Background: Duodenal gastrointestinal stromal tumors (GISTs) are rare, and reports on duodenal GIST bleeding are few. We analyzed the risk factors and clinical outcomes of hemorrhagic duodenal GISTs and compared them with those of gastric GISTs., Methods: Primary duodenal GISTs surgically diagnosed between January 1998 and December 2017 were retrospectively reviewed. Furthermore, patients with duodenal GIST were compared with those with primary gastric GIST histopathologically diagnosed between January 1998 and May 2015 using previously published data., Results: Of the 170 total patients with duodenal GISTs, 48 (28.2%) exhibited tumor bleeding. Endoscopic intervention, embolization, and non-interventional conservative treatment were performed for initial hemostasis in 17, 1, and 30 patients, respectively. The 5-year survival rate was 81.9% in the bleeding group and 89.4% in the non-bleeding group (P = 0.495). Multivariate analysis showed that p53 positivity was a significant risk factor for duodenal GIST bleeding (hazard ratio [HR] 2.781, P = 0.012), and age ≥ 60 years (HR 3.163, P = 0.027), a large maximum diameter (comparing four groups: < 2, 2-5, 5-10, and ≥ 10 cm), and mitotic count ≥ 5/high-power field (HPF) (HR 3.265, P = 0.032) were risk factors for overall survival. The incidence of bleeding was significantly higher in duodenal GISTs than in gastric GISTs (28.2% vs. 6.6%, P < 0.001), and the re-bleeding rate after endoscopic hemostasis was also higher in duodenal GISTs than in gastric GISTs (41.2% vs. 13.3%, P = 0.118)., Conclusion: In patients with duodenal GIST with old age, large tumor diameter, and mitotic count ≥ 5/HPF, a treatment plan should be established in consideration of the poor prognosis, although tumor bleeding does not adversely affect the prognosis. Duodenal GISTs have a higher incidence of tumor bleeding and re-bleeding rate after endoscopic hemostasis than gastric GISTs.

Background: Acid-suppressive agents (ASAs) may be associated with cancer; previous studies reported that the risk of cancer with acid suppressants has differed depending on the site of cancer. Here, we conducted a systematic review and meta-analysis of the association between ASA use and the type of cancer risk., Methods: MEDLINE, EMBASE, and Cochrane library databases were searched for publications up to the end of September 2019 for MeSH terms and text words related to cancer and ASAs. Studies on the association between ASAs and cancer risk, which included a control group and reported the relative risk of cancer, were included. The inverse-variance random effect model was used to estimate the pooled relative risk (RR) and 95% confidence interval (CI), and subgroup analysis for type of acid suppressants, drug uptake duration, and cumulative doses was performed. Heterogeneity was assessed using the I 2 test and Q statistic., Results: Thirty-nine cohort and case-control studies were included. ASA use was found to be significantly associated with a 46% higher risk of gastric cancer (RR, 1.46; 95% CI, 1.18-1.80) and a 53% higher risk of liver cancer (RR, 1.53; 95% CI, 1.31-1.78) compared with nonuse; however, there was no significant association for esophageal, colorectal, pancreatic, lung, breast, prostate, and kidney cancer; melanoma; and lymphoma., Conclusions: ASAs were significantly associated with an increased risk of gastric and liver cancer; therefore, special attention of ASA use considering the potential risk of gastric and liver cancer is needed.

Background: Treatment of locally recurrent gastric neoplasms after endoscopic resection remains challenging. We investigated the efficacy and safety of treatment options for recurrent gastric neoplasms localized to the scar of previous endoscopic submucosal dissection (ESD)., Methods: The clinicopathological characteristics and treatment outcomes of patients who underwent endoscopic treatment or surgery for recurrent gastric neoplasms between June 2010 and May 2017 were retrospectively reviewed., Results: Of the 92 patients included, 74 underwent endoscopic treatment (51 redo ESD, 23 argon plasma coagulation [APC] ablation) and 18 underwent surgery. The redo ESD procedure time was significantly longer than that of the primary ESD (31.0 versus 22.0 min, p = 0.018). Overall, adverse events occurred in 11 patients (12.0%), with the incidence being significantly higher in the surgery group (27.8% versus 8.1% in the endoscopic treatment group, p = 0.036). Local recurrence-free survival rates were 81.1% for the endoscopic treatment group (86.3% and 69.6% for redo ESD and APC groups, respectively) and 100% for the surgery group (log rank p = 0.033). Logistic regression analysis showed that tumor size > 12.5 mm (odds ratio [OR] 5.14, 95% confidence interval [CI] 1.25-26.9, p = 0.032) and tumors located in the upper two-thirds of the stomach (OR 4.43, 95% CI 1.27-16.8, p = 0.023) were associated with non-curative resection after redo ESD., Conclusions: Endoscopic treatment could be an effective and safe alternative to surgery for selected patients with gastric neoplasms recurring at the scar of previous ESD. Especially, patients having small lesions located in the distal part of the stomach could be a good candidate for redo ESD.

Background: Epidemiological studies investigating the use of proton pump inhibitors (PPI) on the risk of liver cancer and/or mortality among persons with chronic liver disease (CLD) have reported conflicting results. We conducted a systematic review and meta-analysis to determine the impact of PPI use on liver cancer and/or death among patients with CLD., Methods: The core databases including MEDLINE, EMBASE, and Cochrane library were searched through January 2020. We included studies, evaluating the association between PPIs and liver cancer or mortality among patients with CLD including randomized controlled, nonrandomized controlled, and observational studies. We used inverse-variance random-effects models to estimate the pooled relative risk (RR) and 95% confidence interval (CI) for liver cancer or mortality., Results: Eleven studies including 173,894 patients were selected. In three studies, individuals with CLD who used PPIs had a 67% greater risk of developing hepatocellular carcinoma (HCC) compared to nonusers (RR, 1.67; 95% CI, 1.12-2.50; I 2  = 92%). Combining data from the eight studies relating PPI to overall mortality, we observed a 57% increased risk of mortality in PPI users with CLD compared to CLD nonusers (RR: 1.57; 95% CI, 1.24-1.99; I 2  = 69%)., Conclusion: PPI use was associated with an increased risk of HCC and mortality in patients with CLD suggesting that PPI prescriptions in patients with CLD should be considered carefully.

Background: Upper gastrointestinal bleeding (UGIB) is one of the major manifestations of gastrointestinal stromal tumor (GIST) of the stomach. Several studies have reported that GIST bleeding is associated with poor prognosis. However, only case reports have reported hemostasis modalities for treating hemorrhagic gastric GIST. To identify clinical outcome of gastric GIST bleeding, we analyzed risk factors and prognosis of hemorrhagic GIST evaluating hemostasis methods., Methods: Total 697 patients histopathologically diagnosed with primary gastric GIST between January 1998 and May 2015 were enrolled to the study, retrospectively., Results: Of 697 total patients, 46 (6.6%) patients had UGIB. Endoscopic intervention, transarterial embolization, or surgical intervention was performed for initial hemostasis in 15, 2, and 1, respectively. Over a median of 68 months of follow-up, 16 patients in bleeding group and 88 patients in non-bleeding group died; the 5-year survival rate was 79.4% in bleeding group and 91.8% in non-bleeding group (p = 0.004). Multivariate analysis showed that significant risk factors for gastric GIST bleeding included the maximal tumor diameter > 5 cm and Ki-67 positivity. Age ≥ 60 [hazard ratio (HR) = 8.124, p = 0.048], necrosis (HR = 5.093, p = 0.027), and bleeding (HR 5.743, p = 0.034) were significant factors for overall survival of gastric GIST patients., Conclusions: Bleeding risk of gastric GIST was higher when tumor had diameter > 5 cm or Ki-67 positivity. In addition, tumor bleeding, necrosis, and age ≥ 60 years were associated with poor overall survival. Endoscopic intervention can be considered as an effective method for initial hemostasis of hemorrhagic gastric GIST.

Here, as a basic study in revealing the correlation between extracellular matrix components and spontaneous abortion, we defined the types of integrins expressed on the surface of endometrial stromal (ES) cells retrieved from the uterus of a patient experiencing spontaneous abortion. For these, the types of integrin subunits in the ES cells retrieved from a woman with spontaneous abortion were identified at the transcriptional and translational levels, and functional assay was conducted for confirming the combinations of integrin α and β subunits. Among the genes encoding 25 integrin subunits, significantly high transcription was seen in integrins α 1 , α 2 , α 3 , α 4 , α 5 , α V , β 1 , β 3 , and β 5 . Translation of integrins α 1 , α 3 , α 5 , α V , and β 1 on the cell surface was detected in almost all ES cells, whereas integrins α 2 , α 4 , β 3 , and β 4 were expressed translationally only in some ES cells. Subsequently, ES cells showed significantly increased adhesion to collagen I, laminin, fibronectin, and vitronectin, and functional blocking of integrin α 1 , α 3 , α 5 , and α V significantly inhibited adhesion to these molecules. These results demonstrated that active heterodimers composed of integrins α 1 β 1 , α 3 β 1 , α 5 β 1 , and α V β 1 were co-localized on the surface of ES cells derived from a patient experiencing spontaneous abortion.

A new triterpene named klodorol B (1), together with six known compounds, were isolated from the green walnut husks of Juglans mandshurica Maxim. Their structures were determined using spectroscopic methods on the basis of 1D and 2D NMR, and high-resolution electrospray ionization mass spectrometry. The isolated compounds were evaluated for their cytotoxic activities on human gastric carcinoma (BGC-823), human liver cancer (HepG-2) and human lung cancer (A549) cell lines. .

Background: Valid and reliable methods for measurement of lesion sizes during endoscopy have not been established., Methods: We developed a novel software program (ENDOVER; Poinbionics, Seoul, Republic of Korea) to measure lesions sizes and assessed its validity and reliability. To validate the program, we measured standard coin sizes and estimated measurement errors. To assess program reliability, 32 pictures of endoscopically resected specimens were used to measure tissue sizes six times in a 24-h interval by two examiners. Intraclass correlation coefficients (ICCs) were used to assess intraobserver and interobserver agreements. Agreement between the program and pathological measurements was assessed by absolute differences., Results: The nominal standard sizes of 10-won, 100-won, and 500-won coins were 18.0, 24.0, and 26.5 mm, and the calculated sizes were 18.09, 24.48, and 26.31 mm, respectively. ICCs of the long and short diameters were, respectively, 0.92 [95% confidence interval (CI) 0.87-0.95] and 0.93 (CI 0.89-0.96) for examiner 1 and 0.88 (CI 0.81-0.93) and 0.92 (CI 0.87-0.95) for examiner 2. Interobserver ICCs of the long and short diameters were 0.97 (CI 0.94-0.99) and 0.97 (CI 0.94-0.99), respectively. The mean absolute differences between the program and pathological measurements were 4.4 and 4.7 mm for the long and short diameters, respectively., Conclusions: Our findings indicate that the novel measurement program is a valid and reliable method for estimation of lesion sizes from endoscopic findings during and after examination.

Background: Postoperative anastomotic bleeding (PAB) is relatively rare; however, it can be lethal if not treated immediately. The aim of our study was to investigate the clinical features of PAB and the efficacy of endoscopic hemostasis (EH) for PAB., Methods: Between January 2004 and May 2013, 16,591 patients underwent gastrectomy for gastric cancer at Asan Medical Center. Among them, 36 patients who experienced PAB within 2 months after the gastrectomy were enrolled as a case group. Each subject was matched at a ratio of 1:5 with randomly selected patients without bleeding during the same period (n = 180, control group). The clinical outcomes and risk factors for patients with PAB were compared with those of the control group, and the results of EH were evaluated retrospectively., Results: The incidence of PAB was 0.22% (n = 36), and the median duration from gastrectomy to PAB was 34.5 h (interquartile range, 12.3-132.8 h). EH was attempted in 25 patients (69.4%); surgery was performed in 6 patients (16.7%); and conservative management was applied in 5 patients (13.9%). PAB-related death occurred in three patients (8.3%; one in each treatment modality). Among 25 patients with primary EH, 16 were treated successfully (64%) and hemoclip was the most commonly used endoscopic tool (52%). In the multivariate analysis, the type of gastrectomy was found to be a risk factor for PAB (odds ratio 3.448, 95% confidence interval, 1.138-10.448, p = .029)., Conclusions: Although PAB is an infrequent and potentially life-threatening complication, endoscopy can be considered as a useful method to avoid additional surgery in properly selected patients.

Background: The association between obesity and albuminuria in the general population remains unclear. We aimed to identify the association between obesity and albuminuria as well as sex differences regarding the associations using several obesity indices, including waist circumference (WC), body mass index (BMI), and waist-to-height ratio (WHR)., Methods: This study included 3841 subjects (1730 males and 2111 females; age 20-80 years) who participated in the Fifth Korea National Health and Nutrition Examination Survey conducted in 2011. Subjects with hypertension, diabetes, renal failure, or a malignant tumor and those who were pregnant or menstruating were excluded. Albuminuria was defined as a urinary albumin-to-creatinine ratio ≥30 mg/g. Anthropometric parameters were categorized into sex-specific quartiles. Logistic regression models were used to assess the associations between each anthropometric parameter and albuminuria., Results: All of the obesity indices of the fourth quartile group of females showed a twofold higher risk for albuminuria than the second quartile group, and it was persistently significant after adjusting for age, smoking, and physical activity. After further adjustment for high blood pressure and impaired fasting glucose and triglyceride levels, WC and BMI of the fourth quartile group of females still showed a significantly higher risk for albuminuria than the second quartile group (odds ratios 1.96 and 2.24; 95 % confidence intervals 1.03-3.74 and 1.15-4.37). None of the associations between albuminuria and the obesity indices were significant in males., Conclusion: Higher WC and BMI were significantly associated with the risk of albuminuria among females, but not males., Competing Interests: None of the authors have competing interests to declare.

Background: The incidence of metachronous lesions after endoscopic resection (ER) of high-grade dysplasia (HGD) has not been evaluated, and optimal surveillance strategy remains vague. This study aimed to evaluate the incidence and characteristics of metachronous tumors including HGD and early gastric cancer (EGC) arising after ER., Patients: The medical records of 2779 patients with 2981 lesions (445 patients with HGD and 2334 patients with EGC) who underwent ER and surveillance endoscopy at Asan Medical Center between April 1999 and December 2011 were retrospectively reviewed, and clinicopathological features of metachronous tumors were analyzed., Results: Ninety-six metachronous lesions (17 HGD and 79 EGC) occurred in 92 patients during median 42 months of follow-up period (range 26-58 months). The 5-year and 10-year overall cumulative incidences of metachronous tumors were 4.6 and 10.5 %, respectively, and were on steady rise up to 10 years. The 5- and 10-year cumulative incidences of metachronous lesions were 4.1 and 8.4 % in HGD group and 4.7 and 11.3 % in EGC group (P = 0.578), respectively. The size of metachronous tumors was significantly smaller than initial lesion (2.3 vs. 1.9 cm, P = 0.039). Lower third of the stomach was most frequent site for both initial and metachronous lesions (77.1 and 70.8 %, respectively) and age was the significant predicting factor for metachronous tumors., Conclusions: Cumulative incidence of metachronous tumors after ER of HGD was comparable to the incidence after ER of EGC. Surveillance endoscopy can be considered at least for 10 years, with special attention on the lower third of the stomach.

Purpose: This study aimed to evaluate the effectiveness and safety of ramosetron for chemotherapy-induced nausea and vomiting (CINV) through a systematic review of randomized controlled trials (RCTs)., Methods: An electronic search of CENTRAL, Ovid MEDLINE, Ovid EMBASE, KoreaMed, KISS, KMbase, and DBpia was performed. Published RCTs comparing ramosetron treatment and other 5-HT3RAs to prevent CINV were included, and studies reporting at least one clinical outcome about efficacy were included. Assessment of risk of bias and data extraction of the included studies was conducted by two independent reviewers., Results: Sixteen RCTs were included, with nine studies reporting nausea and 13 reporting vomiting. In the acute phase, ramosetron significantly reduced nausea compared to other 5-HT3RAs (RR 1.11; 95 % CI 1.10 to 1.22, P = 0.03), as well as acute vomiting (RR 1.04, 95 % CI 1.01 to 1.08, P = 0.02). In the delayed phase, there was no difference in the complete response of nausea between ramosetron and other 5-HT3RAs, whereas ramosetron significantly decreased emesis compared to other 5-HT3RAs. Also, there were no significant differences between ramosetron versus other 5-HT3RAs for common adverse reactions such as headache, diarrhea, dizziness, and constipation., Conclusions: This study's findings suggest that ramosetron for CINV is as effective and tolerable as other 5-HT3RAs, based on the currently available evidence from RCTs. However, owing to methodological flaws in the current RCTs, well-designed randomized controlled trials are needed to confirm the effect of ramosetron on acute or delayed CINV in cancer patients.

Background/aims: Self-expandable metal stents (SEMSs) can be used for the palliation of malignant obstruction in the upper gastrointestinal tract. This study assessed the feasibility and efficacy of endoscopically inserted SEMSs for the palliation of malignant obstruction in the stomach and duodenum., Methods: Between January 2011 and April 2014, 220 patients with gastric or duodenal obstruction due to malignancy underwent endoscopic SEMS insertion at Asan Medical Center. The associations of technical/clinical outcomes and complications with the type of stent and site of obstruction were analyzed., Results: The 220 patients included 125 men (56.8 %) and 95 women (43.2 %); median patient age was 63 years. Fully covered, partially covered, and uncovered SEMSs were inserted into 16, 77, and 120 patients, respectively. Obstructions were located in the gastric outlet, including the duodenal bulb, in 106 patients, and in the duodenal second and third portions in 114 patients. Technical success was achieved in 213 of 220 patients (96.8 %) and clinical success in 184 of 213 (86.4 %). Clinical success rates were similar to the type of stent, but were significantly greater for gastric outlet (95/104, 91.3 %) than for duodenal (89/109, 81.7 %) obstructions (p = 0.039). Stent migration was observed in 20 patients (9.1 %) and stent obstruction in 51 (23.2 %). Rates of stent migration were significantly higher for fully covered (6/16, 37.5 %) than for partially covered (7/77, 9.1 %) and uncovered (7/120, 5.8 %) SEMSs (p < 0.001) and were significantly higher for gastric outlet (16/104, 15.4 %) than for duodenal (4/109, 1.2 %) obstructions (p = 0.003). Rates of stent obstruction were similar for fully covered (2/16, 12.5 %), partially covered (17/77, 22.1 %), and uncovered (32/120, 26.7 %) SEMSs (p = 0.409) and in patients with gastric outlet (26/104, 25.0 %) and duodenal (25/109, 22.9 %) obstruction (p = 0.724)., Conclusions: SEMS selection for malignant obstruction of the upper gastrointestinal tract depends on the site of obstruction.

Background: Bleeding is a major complication following endoscopic resection (ER) of gastric mucosal lesions. We aimed to determine the risk factors for post-ER bleeding and their correlations according to the time elapsed since the procedure., Methods: We retrospectively enrolled 670 lesions in 610 patients who underwent ER between March 2009 and December 2010. We classified these lesions into three types in accordance with the bleeding time, i.e., immediate bleeding (IB), early delayed bleeding (EDB), and late delayed bleeding (LDB). We analyzed the risk factors for each bleeding type according to baseline patient characteristics, procedure-related factors, and correlations between the occurrence of each bleeding type., Results: There were 408 post-ER bleeding events in our study cohort: 302 IB events, 88 EDB events, and 18 LDB events. In multivariate analysis, a histologic finding of carcinoma and the resection time were significant predictors of IB (p < 0.001). Of the 302 IB events, 13.9% showed EDB. Additionally, LDB occurred in 2.4% of lesions with EDB and 4.6% of lesions without EDB. Similar to the IB group, of 368 lesions without IB, 12.5% showed EDB. In addition, LDB occurred in 2.2% of lesions with EDB and 1.2% of lesions without EDB. IB was associated with a higher risk of EDB (p < 0.001) and LDB (p < 0.001), whereas EDB was not related to an increased risk of LDB (p = 0.997)., Conclusion: IB significantly increases the risk of EDB and LDB, but EDB does not increase the risk of LDB. Histologically confirmed carcinoma or a prolonged time for resection increases the risk of post-ER IB. We recommend careful follow-up approaches following ER of a gastric mucosal lesion in high-risk patients to prevent a potentially critical occurrence of delayed bleeding.

Background: Endoscopic resection for gastric neoplasms in the pylorus is a technically difficult procedure. We investigated clinical outcomes to determine the feasibility and effectiveness of endoscopic resection for gastric neoplasms in the pylorus., Methods: Subjects who underwent endoscopic resection for gastric neoplasms in the pylorus between January 1997 and February 2012 were eligible., Results: A total of 227 subjects underwent endoscopic resection for 228 gastric adenomas and early cancers in the pylorus. En bloc resection was achieved for 193 lesions (84.6%), including complete resection of 195 lesions (85.5%), and curative resection of 167 lesions (73.2%). Complete resection and curative resection rates were significantly different according to the location (prepyloric, pyloric, and postpyloric, P = 0.002 and P = 0.006). Delayed bleeding and stricture occurred in 5.3 and 3.1%, respectively, and there was no patient with perforation. During a median follow-up period of 79.0 months, local tumor recurrence was detected in 2.6%., Conclusions: Endoscopic resection appears to be a feasible and effective method for the treatment of pyloric neoplasms, regardless of the location and distribution of tumor. Thorough evaluation of the distal margin of the tumors is necessary when tumors involve or extend beyond the pyloric ring, and the appropriate use of additional techniques may be useful.

Background: The use of endoscopic submucosal dissection (ESD) for the treatment of minute submucosal (SM) invasive cancer that fulfills the current expanded criteria remains controversial. This study investigated the clinicopathological parameters of patients with sm1 gastric cancers to predict lymph node metastasis (LNM) and evaluate the feasibility of ESD as a curative treatment., Methods: Data from 278 patients who underwent surgical resection of sm1 gastric cancer between 2006 and 2010 were retrospectively collected, and their clinicopathological parameters were analyzed to identify predictive factors of LNM., Results: Of 278 patients, 28 patients (10.1 %) had LNM. Multivariate analysis identified multiple lesions (p = 0.018), lymphovascular invasion (LVI) (p < 0.001), SM invasion depth >500 µm (p = 0.007), undifferentiated histology (p = 0.012), and ulceration (p = 0.024) as factors significantly associated with LNM in patients with sm1 gastric cancer. Additionally, SM invasion width/superficial tumor size ratio >0.04 (p = 0.036) demonstrated a significant association with LNM in patients with sm1 gastric cancer falling within the current expanded criteria for ESD. LNM was not identified among 35 patients who met the absence of ulceration, SM invasion depth ≤ 500 µm, and SM invasion width/superficial tumor size ratio ≤ 0.04 besides the current expanded indications., Conclusions: Endoscopic resection can be performed on patients with minute SM invasive, differentiated cancers of ≤ 3 cm without LNM on pretreatment examination. In addition, if histological assessment shows the absence of LVI and ulceration, SM invasion depth ≤ 500 µm, and SM invasion width/superficial tumor size ratio ≤ 0.04, the patient can be carefully observed without additional treatment.

To save and analyze the data from a positron emission tomography/computed tomography (PET/CT) scan, it is sometimes important to use a server away from the workstation of the equipment or to install and operate mini-picture archiving and communication system (PACS). Mini-PACS was developed to save the data from a scan and measure the standard uptake value (SUV) in PACS that could be measured only in PET/CT equipment manufactured by many companies. Against this background, this study examined whether the SUV measured in PET/CT equipment was the same value in mini-PACS. This study evaluated Biograph 16 and Biograph 40 manufactured by SIEMENS and Discovery Ste 8 manufactured by GE, all of which are installed in this hospital. The SUV of the aorta of 30 patients, who had undergone an (18)F-FDG whole body PET scan in the period from February to October 2012, was measured at the height of the liver and mediastinum. In the mini-PACS program, the SUV was also measured and analyzed in an image with the same phase. According to the study results, the coefficient of the SUV of the liver in PET/CT equipment and mini-PACS was 0.99, 0.98, and 0.64 in Biograph 16, Biograph 40, and Discovery Ste 8, respectively, where the coefficient of the SUV of aorta was 0.98, 0.98, and 0.66 in Biograph 16, Biograph 40, and Discovery Ste 8, showing a positive correlation in all equipment.

An excellent transparent film with effective absorption property in near-infrared (NIR) region based on cesium-doped tungsten oxide nanoparticles was fabricated using a facile double layer coating method via the theoretical considerations. The optical performance was evaluated; the double layer-coated film exhibited 10% transmittance at 1,000 nm in the NIR region and over 80% transmittance at 550 nm in the visible region. To optimize the selectivity, the optical spectrum of this film was correlated with a theoretical model by combining the contributions of the Mie-Gans absorption-based localized surface plasmon resonance and reflections by the interfaces of the heterogeneous layers and the nanoparticles in the film. Through comparison of the composite and double layer coating method, the difference of the nanoscale distances between nanoparticles in each layer was significantly revealed. It is worth noting that the nanodistance between the nanoparticles decreased in the double layer film, which enhanced the optical properties of the film, yielding a haze value of 1% or less without any additional process. These results are very attractive for the nanocomposite coating process, which would lead to industrial fields of NIR shielding and thermo-medical applications., Pacs: 78.67.Sc; 78.67.Bf; 81.15.-z.

The purpose of this study was to examine the conceptual gap between self-perceived weight and body mass index (BMI), and to assess the knowledge gap between perceived importance of following dietary guidelines and health literacy levels. Adults (n = 131) eligible for the Supplemental Nutrition Assistance Program (SNAP) were interviewed at eleven SNAP regional offices in Maryland. Based on BMI calculated from self-reported height and weight, 65.6% of participants were overweight or obese while 40.5% perceived that they were overweight or obese. In sub-group analysis categorized by BMI, only 20.0% in the overweight and 20.0% in the obese group correctly perceived themselves as being overweight or obese. Following dietary guidelines was perceived as important by a majority of participants, but only 43.5% had adequate health literacy. Conceptual and knowledge gaps between self-perception and objective health status existed in the low-income SNAP-eligible sample. Future studies need to address these gaps because misperceived weight status and insufficient health literacy are critical barriers to inducing behavioral change.

Background: Endoscopic forceps biopsy (EFB) is a major diagnostic procedure for gastric epithelial neoplasia (GEN). However, discrepancy between the result of EFB and endoscopic resection (ER) is not uncommon. Thus, there is controversy over whether specimens obtained by EFB are optimal for diagnosis of GEN. We investigated the discrepancy between EFB and ER in the diagnosis of GEN., Methods: A total of 1,850 GEN cases were histologically diagnosed with EFB, including 954 low-grade dysplasias (LGDs), 315 high-grade dysplasias (HGDs), and 581 carcinomas. Following diagnosis with EFB, all patients were treated with ER. We retrospectively reviewed the pathologic findings and patient characteristics and analyzed predictors for the discrepancy between the two procedures (largest diameter, number of biopsy fragments, number of biopsy fragments/largest diameter, location, macroscopic type, color, surface unevenness, and erosion)., Results: The overall discrepancy rate between EFB and ER was 31.7 % (587/1,850). Among the discordant group, 440 (23.9 %) cases showed a higher grade of disease after ER; 229 of the 954 LGDs (24.0 %) were diagnosed as HGD or carcinoma, 166 of the 315 HGDs (52.7 %) as carcinoma, and 45 of the 581 differentiated carcinomas (7.7 %) as undifferentiated carcinoma. In the LGD group with EFB, the largest diameter (≥1.8 cm; P < 0.001), surface unevenness (P = 0.014), and depressed macroscopic type (P < 0.001) were factors associated with discrepancy. In the carcinoma group with EFB, flat macroscopic type (P = 0.043) was the only significant factor. In the HGD group with EFB, there were no significant factors for discrepancy., Conclusions: EFB can be insufficient for diagnosing GENs, and ER can be considered not only as treatment but also as a diagnostic modality in GEN. It is especially pertinent to all cases of HGD regardless of their endoscopic features and to cases of LGDs with the largest lesion diameter ≥1.8 cm, surface unevenness, or a depressed macroscopic type.

Background: The purpose of this study was to evaluate the safety and efficacy of endoscopic therapy, an alternative and less invasive modality for the management of leakage after gastrectomy., Methods: An electronic database of 35 patients with anastomotic leaks after surgery for stomach cancer that were treated with either an endoscopic procedure or surgery between January 2004 and March 2012 was reviewed. The success rates and safety of both modalities were evaluated., Results: Endoscopic treatment was performed in 20 patients and surgical treatment in 15 patients. The median time interval between the primary surgery and diagnosis of leakage was 8.0 days (interquartile range, 5.0-14.0 days). Of the 20 patients with endoscopic treatment, technical success was achieved in 19 patients (95 %) with resulting clinical success achieved in all of these 19 patients (100 %). One patient with failed endoscopic management went on to receive surgery. There were no cases of leakage-related deaths after endoscopic treatment. Of the 15 patients with surgical treatment, 5 died due to sepsis, bleeding, or hospital-acquired pneumonia. For diagnosis of leakage, 17 patients from the endoscopy group underwent computed tomography (CT) scanning, which revealed leakages in 3 patients (17.6 %) and occult leakages were subsequently defined at fluoroscopy in all 20 patients. Seven of twelve patients (58.3 %) from the surgical group had leakages diagnosed by CT scan., Conclusions: Endoscopic treatment can be considered a valuable option for the management of postoperative anastomotic leakage with a high degree of technical feasibility and safety, particularly for leakages that are not excessively large.

Elders living alone may experience worse health outcomes than do those living with spouse and/or children. Using baseline data from a randomized trial to promote high blood pressure (HBP) control in Korean elders (N = 440), we examined the relationship between living arrangements and HBP control. We also interviewed a sub-sample to better understand the patterns of social interactions associated with different types of living arrangements. One in five reported living alone; this group tended to be older and female, and resided in senior group housing. Those living alone were twice as likely as those living with a spouse to have controlled BP (OR = 2.08; 95 % CI 1.09-3.97), even after controlling for study covariates. Those in senior group housing had frequent social interactions that involved conversations around health, encouragement concerning medication taking, and health information sharing. In conclusion, Korean elders living independently are neither socially-isolated nor at increased risk for poor BP control.

Background: There are insufficient reports on the outcomes and local recurrence rates for gastric neoplasms treated using argon plasma coagulation (APC). The purpose of this study was to analyze the clinical outcomes in early gastric cancer or gastric adenoma patients following APC treatment., Methods: Seventy-one patients were enrolled and all underwent APC at the Asan Medical Center between July 2007 and August 2011. Clinical and oncological outcomes were analyzed., Results: The median follow-up period was 20 months (interquartile range 13-29 months). Among the 71 patients we evaluated, nonlifting after submucosal saline injection was found in 35 patients and 15 patients (21.2%) experienced local recurrence with a median period of 10 months (IQR 5-13 months). The rate of local recurrence was higher in the nonlifting group and the 40-W group than in the lifting group and the 60- or 80-W groups (31.4 vs. 11.1%, p = 0.045 and 31.7 vs. 6.7%, p = 0.017, respectively). Multivariate analysis showed that the power setting with the 40-W and nonlifting groups after submucosal injection was associated with local recurrence., Conclusions: APC therapy after submucosal saline injection using high power (60 or 80 W) appears to be an effective alternative in the management of gastric neoplasm.

Background: The outcomes of balloon dilation for the treatment of strictures caused by endoscopic submucosal dissection (ESD) have not been evaluated previously. This study was designed to evaluate and compare the effectiveness and complications of balloon dilation for post-ESD strictures and peptic strictures., Methods: The medical records of 14 patients with post-ESD strictures and 48 patients with peptic strictures who underwent fluoroscopically or endoscopically guided balloon dilation between January 1997 and April 2011 at the Asan Medical Center in Korea were reviewed retrospectively., Results: The technical success rates (defined as successful dilation without major complications) of the post-ESD and peptic stricture groups were 92.9% (13/14) and 93.8% (45/48), respectively (p = 1.000). For the post-ESD and peptic stricture groups, the clinical success rates (defined as symptom improvement, as determined by the patient) at 1 month were 92.9% (13/14) and 83.3% (40/48), respectively (p = 0.67). Their clinical success rates at 6 months were 71.4% (10/14) and 70 % (28/40), respectively (p = 1.000). The mean weight gains of the post-ESD stricture group 1 and 6 months after balloon dilation were 1.1 and 4.8 kg, respectively, whereas the peptic group gained 1.4 and 3.4 kg, respectively (p = 0.814). All complications were perforations. The complication rates of the post-ESD and peptic stricture groups were 7.1 % (1/14) and 10.5 % (5/48), respectively (p = 1.000)., Conclusions: Balloon dilation is an effective and safe treatment for post-ESD strictures.

The impact of CDH1 gene mutations and large deletions on hereditary diffuse gastric cancer (HDGC) and early onset diffuse gastric cancer (EODGC) has not been determined in Asians. We investigated the mutation status of the CDH1 gene in 25 Korean EODGC patients younger than 50 years and 23 HDGC patients who met the clinical criteria for HDGC. Polymerase chain reaction-direct sequencing was performed, and multiplex ligation-dependent probe amplification (MLPA) was used to evaluate the patients with negative sequencing results. We determined that 2 of 25 (8 %) EODGC patients had CDH1 germline mutations. One was a nonsense mutation (c.1003C>T, p.Arg335*, exon 7) in a 41-year-old female with no family history of cancer. The other was a missense mutation (c.715G>A, p.Gly239Arg, exon 6) in a 28-year-old male with no family history of cancer. One of 23 (4.3 %) HDGC patients had a CDH1 germline mutation (c.1003C>T). The patient's brother and sister died of stomach cancer. The MLPA results revealed no deletion or duplication in any patient. More research is needed to determine additional genetic targets that trigger HDGC. More comprehensive methods such as next-generation sequencing might be a good approach that can be used to identify the genetic causes of pathogenetically unexplained disorders.

Background: The main problem in performing endoscopic submucosal dissection (ESD) of gastric neoplasms is that it is technically difficult, especially for beginners., Methods: A total of 51 patients were randomly assigned to undergo transnasal endoscope-assisted or routine ESD performed by two endoscopists inexperienced in ESD while supervised by one expert., Results: Total procedure time (p = 0.330), complete resection rate (p = 0.977), and complication rate (p = 0.157) were similar for the patients who underwent transnasal endoscope-assisted and routine ESD, but bleeding control time was significantly longer in the transnasal endoscope-assisted ESD group (p = 0.002). Three and six patients in the transnasal endoscope-assisted and routine ESD groups, respectively, were "dropped out" during the procedures (p = 0.291). The endoscopists tended to regard the traction with the transnasal endoscope as more useful for large tumors (p = 0.062). Bleeding control in patients who underwent the transnasal endoscope-assisted ESD was significantly longer for patients with tumors located in the anterior wall, posterior wall, and lesser curvature of the stomach (p = 0.001)., Conclusion: Transnasal endoscope-assisted ESD does not result in improved outcomes when performed by beginners, except for some large tumors. The traction method used by beginners was not superior to proper supervision and advice by an expert during ESD and allowing the expert to perform the procedure when the risk of complications is high or the procedure is delayed.

Background: Reducing food residue by proper preparation methods before endoscopy after distal gastrectomy can increase the quality of examination and decrease patient discomfort. We evaluated the risk factors for food residue and proper methods of preparation for endoscopy after distal gastrectomy., Methods: Follow-up endoscopy with questionnaires was performed on 1,001 patients who underwent distal gastrectomy at Asan Medical Center between December 2010 and July 2011., Results: Endoscopic examination failed in 94 patients (9.4 %) as a result of large amounts of food residue. Rates of failure were significantly higher in patients who ate a regular diet rather than a soft diet at last dinner before examination (13.9 vs. 6.1 %, p = 0.050), and in those who ate lunch rather than not eating lunch on the day before examination (14.6 vs. 7.7 %, p = 0.020). Multivariate analysis showed that the rate of failed examination was lower in patients who had a history of abdominal surgery (p = 0.011), those who ate a soft (p < 0.001) or liquid (p = 0.003) diet as a last meal rather than a regular diet, those who underwent Billroth I rather than Billroth II reconstruction (p = 0.035), patients with longer fasting time (p = 0.009), and those with a longer gastrectomy-to-endoscopy time interval (p < 0.001)., Conclusions: Patients who undergo follow-up endoscopy after surgery should fast more than 18 h and ingest a soft or liquid diet on the day before examination.

Aim: Monocyte chemoattractant protein-1 (MCP-1) is a potent chemokine and plays an important role in atherosclerosis of Type 2 diabetes. The aim of this study was to investigate the methylation status of CpG sites in the MCP-1 promoter in Type 2 diabetic patients and its correlation to serum MCP- 1 level, and blood glucose level., Methods: The 32 patients with Type 2 diabetes and 15 healthy controls were enrolled into the study. Bodymass index, blood pressure, blood lipid, blood glucose, glycosylated hemoglobin (HbA1c), and serum MCP-1 were measured. Genomic DNA was isolated fromthe peripheral blood mononuclear cells (PBMC). Methylation status of CpG sites in theMCP-1 promoter was determined using methylation specific polymerase chain reaction., Results: The promoter region (2890-3050 bp) was predominantly methylated in PBMC from controls.Methylation of CpGmotifs were less methylated in the patients than in the controls (25% vs 80%; p<0.001), while the level of MCP-1 in serum was higher in patients with Type 2 diabetes (193.95±74.96 vs 88.46±55.10; p<0.001). MCP-1 promoter methylation was significantly correlated to serum MCP-1, HbA1c, fasting blood glucose, and triglyceride., Conclusion: These data suggest that hypomethylation of CpG sites in the MCP-1 promoter region may be affected by blood glucose and TG, which then increase the serum MCP-1 level and may play a role in the vascular complications of Type 2 diabetes.

Purpose: The aim of this study was to determine whether (18)F-fluorothymidine (FLT) PET is feasible for the early prediction of tumor response to induction chemotherapy followed by concurrent chemoradiotherapy in patients with esophageal cancer., Methods: This study was prospectively performed as a collateral study of "randomized phase II study of preoperative concurrent chemoradiotherapy with or without induction chemotherapy with S-1/oxaliplatin in patients with resectable esophageal cancer". (18)F-FLT positron emission tomography (PET) images were obtained before and after two cycles of induction chemotherapy, and the percent change of maximum standardized uptake value (SUVmax) was calculated. All patients underwent esophagography, gastrofiberoscopy, endoscopic ultrasonography (EUS), computed tomography (CT) and (18)F-fluorodeoxyglucose (FDG) PET at baseline and 3-4 weeks after completion of concurrent chemoradiotherapy. Final tumor response was determined by both clinical and pathologic tumor responses after surgery., Results: The 13 patients for induction chemotherapy group were enrolled until interim analysis. In a primary tumor visual analysis, the tumor detection rates of baseline (18)F-FLT and (18)F-FDG PET were 85% and 100%, respectively. The tumor uptakes on (18)F-FLT PET were lower than those of (18)F-FDG PET. Among nine patients who completed second (18)F-FLT PET, eight patients were responders and one patient was a non-responder in the assessment of final tumor response. The percent change of SUVmax in responders ranged from 41.2% to 79.2% (median 57.1%), whereas it was 10.2% in one non-responder., Conclusion: The percent change of tumor uptake in (18)F-FLT PET after induction chemotherapy might be feasible for early prediction of tumor response after induction chemotherapy and concurrent chemoradiotherapy in patients with esophageal cancer.

Nardostachys jatamansi (NJ) has been used in the treatment of inflammatory diseases. However, it is not clear how NJ produces anti-inflammatory effects. In the present study, using an experimental model of lipopolysaccharide (LPS)-induced endotoxin shock, the protective effects and mechanisms of action of NJ were investigated. The water extract of roots of NJ was administrated to mice orally (1, 5, and 10 mg/kg) 1 h after or before LPS challenge. The administration of NJ inhibited LPS-induced endotoxin shock and the production of inflammatory mediators, such as interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, and interferon (IFN)-α/β. Murine peritoneal macrophages were used to determine the production of inflammatory mediators. In peritoneal macrophages, NJ also inhibited LPS-induced production of inflammatory mediators, such as IL-1β, IL-6, TNF-α, and IFN-α/β. In addition, NJ reduced the activation of mitogen-activated protein kinases (MAPKs) and the level of expression of interferon regulatory factor (IRF)-1 and IRF-7 mRNA. Furthermore, post-treatment with NJ reduced LPS-induced endotoxin shock and the production of inflammatory mediators. These results suggest that NJ inhibits endotoxin shock by inhibiting the production of IL-1β, IL-6, TNF-α, and IFN-α/β through the inhibition of MAPKs activation and IRF induction.

Despite well-known benefits of health care utilization for the effective management of chronic diseases, the underlying mechanism of understanding health care utilization in ethnic minority population has not been systematically explored. The purpose of this paper is to examine the predictive ability of a health care utilization model by analyzing the interplay between predisposing, enabling, and need factors. The sample consisted of hypertensive Korean American immigrants (KAIs) 40-64 years of age who participated in a self-help intervention for high blood pressure care (SHIP-HBP). Using structured questionnaires, data were collected from 445 KAIs at baseline and analyzed with path analysis. Insurance status and relevant medical history were not just strong direct effects but also carried the most total effect on the health care utilization of these patients. Life priorities, years of residence in the US and perceived income level exerted indirect effects through the participants' insurance status. Our statistical analysis indicated a good fit for the proposed model (x (2) = 28.4, P = 0.29; NFI = 0.91; CFI = 0.99; RMSEA = 0.02). Overall, the model explained 18% of the variance in health care utilization of hypertensive KAIs. These findings strongly support a need to improve access to health care for KAIs by introducing a variety of community resources and building sustainable community infrastructures.

Background: Bleeding is a major complication of endoscopic mucosal resection (EMR). This study investigated whether the use of metal hemoclips to close EMR-induced ulcers after gastric EMR was effective in preventing delayed bleeding., Methods: This single-center study retrospectively examined the records for 150 lesions of 140 consecutive patients (107 men and 33 women) with a mean age of 61 years (range, 38-81 years) who underwent EMR. For 60 patients, moderate to severe immediate bleeding occurred during the procedure, and the ulcers had been closed using metal hemoclips (clip group). In the remaining 90 cases, the immediate bleeding was absent or mild, and hemoclips were not used (nonclip group). Postprocedure bleeding (delayed bleeding) was analyzed., Results: Overall, delayed bleeding occurred with 14 (9.3%) of the 150 lesions. Delayed bleeding occurred less frequently in the clip group (2 of 60 lesions; 3.3%) than in the nonclip group (12 of 90 lesions; 13.3%; p = 0.04). Of the 60 clip group ulcers, 37 (62%) were completely closed, and none showed delayed bleeding. The median number of hemoclips used for ulcer closure was 10 (range, 4-22), and the median time for ulcer closure was 14 min (range, 4-40 min)., Conclusions: Prophylactic closure of gastric EMR-induced ulcers with hemoclips reduced delayed bleeding.

In this study, we characterized the surface of oxide film formed on titanium metal through the use of thermal treatment and investigated the effect of surface characteristics on the bioactivity of titanium. The as-received sample group was prepared by polishing and cleaning CP-Ti as a control group, and thermally oxidized sample groups were prepared by heat treating at 530, 600, 700, 800, 900, and 1000 degrees C respectively. Micro-morphology, crystalline structure, chemical composition, and binding state were evaluated using FE-SEM, XRD, and XPS. The bioactivity of sample groups was investigated by observing the degree of calcium phosphate formation from immersion testing in MEM. The surface characterization tests showed that hydroxyl group content in titanium oxide film was increased, as the density of titanium atoms was high and the surface area was large. In MEM immersion test, initial calcium phosphate formation was dependent upon the thickness of titanium oxide, and resultant calcium phosphate formation depended on the content of the hydroxyl group of the titanium oxide film surface.

Background: The aim of this study was to determine how to select potential candidates for curative resection among advanced gastric patients with equivocal findings of para-aortic lymph node metastasis on computed tomography (CT)., Methods: We analyzed the clinicopathologic results of 23 advanced gastric cancer patients who were diagnosed as having equivocal findings of para-aortic lymph node metastasis on a CT scan and who underwent gastrectomy with D2 and para-aortic lymph node dissection., Results: Twenty-two patients were male, and one patient was female. The median age of all study subjects was 52 years (range, 31-75 years). Sixteen underwent total gastrectomy, and seven underwent subtotal gastrectomy. The median number of A2 (suprarenal) lymph nodes harvested was 2 (range, 1-5), and that of B1 (infrarenal) lymph nodes was 6 (range, 1-17). Ten (43.5%) of the 23 patients were proven pathologically to have metastasis to para-aortic lymph nodes. Two patients with cT2 cancer had no metastatic para-aortic lymph node, whereas three patients with cT4 disease had metastatic para-aortic lymph nodes (P = .021). Seven (70.0%) of 10 patients with pathologic para-aortic lymph node metastasis experienced recurrence, whereas only 2 (15.4%) of 13 patients without experienced recurrence (P = .008). The Lauren classification was found to be an independent predictor of para-aortic lymph node metastasis (relative risk; .13; 95% confidence interval, .02-.83; P = .03)., Conclusions: More than half of gastric cancer patients with equivocal findings of para-aortic lymph node metastasis on CT are potential candidates for curative resection. The Lauren classification of gastric cancer in patients with equivocal CT findings of para-aortic lymph node metastasis would be helpful when deciding on clinical stage and treatment plans in these patients.

Pure red cell aplasia (PRCA) associated with adult-onset Still's disease (AOSD) is very rare. In this report a 28-year-old woman was admitted with fever, skin rash, jaundice and anemia. She was diagnosed as having AOSD with PRCA by bone marrow examination. Treatment with high-dose prednisolone and intravenous immunoglobulin resulted in remission of the PRCA and a good response of the AOSD.