To clarify the role of neoadjuvant concurrent chemoradiotherapy (NACCRT) followed by surgical resection for localized or locally advanced perihilar cholangiocarcinoma (CCA).METHODSWe retrospectively reviewed 57 patien...To clarify the role of neoadjuvant concurrent chemoradiotherapy (NACCRT) followed by surgical resection for localized or locally advanced perihilar cholangiocarcinoma (CCA).METHODSWe retrospectively reviewed 57 patients who underwent surgical resection with or without NACCRT for perihilar CCA; 12 patients received NACCRT and 45 patients did not received NACCRT. Patients with locally advanced perihilar CCA requiring NACCRT were defined as follows: (1) a mass involving unilateral branches of the portal vein or hepatic artery with insufficient volume of the anticipated remnant lobe; or (2) an infiltrating mass in the main portal vein that was too long for reconstruction, identified at preoperative staging.RESULTSThe median disease-free survival (DFS) durations of the neoadjuvant and non-neoadjuvant CCRT groups were 26.0 and 15.1 mo, respectively (P = 0.91). The median overall survival (OS) durations of the neoadjuvant and non-neoadjuvant CCRT groups were 32.9 and 27.1 mo, respectively (P = 0.26). The NACCRT group showed a downstaging tendency compared to the non-NACCRT group as compared with the tumor stage confirmed by histological examination after surgery and the tumor stage confirmed by imaging test at the time of diagnosis (P = 0.01).CONCLUSIONNACCRT does not prolong DFS and OS in localized or locally advanced perihilar CCA. However, NACCRT may allow tumor downstaging and improve tumor resectability.展开更多
AIM:The generation of oxygen free radicals has been implicated in the pathogenesis of experimental pancreatitis. The aim of this study was to determine the role of oxygen free radicals in patients with acute pancreati...AIM:The generation of oxygen free radicals has been implicated in the pathogenesis of experimental pancreatitis. The aim of this study was to determine the role of oxygen free radicals in patients with acute pancreatitis. METHODS:The plasma levels of C-reactive protein(CRP), lipid peroxide(LPO),myeloperoxidase(MPO)and superoxide dismutase(SOD)were measured in 13 patients with acute pancreatitis and 14 healthy volunteers. RESULTS:Among the patients with acute pancreatitis,there were higher plasma levels of LPO and MPO and lower SOD activity in patients with severe pancreatitis than in those with mild pancreatitis.However,there was no significant difference in the serum marker of oxidative stress no matter what the etiology was.The LPO level was especially correlated with the concentration of serum CRP and CT severity index. CONCLUSION:The oxygen free radicals may be closely associated with inflammatory process and the severity of acute pancreatitis.Especially,the concentration of plasma LPO is a meaningful index for determining the severity of the disease.展开更多
Endogenous neural stem cells become ＂activated＂ after neuronal injury, but the activation sequence and fate of endogenous neural stem cells in focal cerebral ischemia model are little known. We evaluated the relatio...Endogenous neural stem cells become ＂activated＂ after neuronal injury, but the activation sequence and fate of endogenous neural stem cells in focal cerebral ischemia model are little known. We evaluated the relationships between neural stem cells and hypoxia-inducible factor-1α and vascular endothelial growth factor expression in a photothromobotic rat stroke model using immunohistochemistry and western blot analysis. We also evaluated the chronological changes of neural stem cells by 5-bromo-2′-deoxyuridine（BrdU） incorporation. Hypoxia-inducible factor-1α expression was initially increased from 1 hour after ischemic injury, followed by vascular endothelial growth factor expression. Hypoxia-inducible factor-1α immunoreactivity was detected in the ipsilateral cortical neurons of the infarct core and peri-infarct area. Vascular endothelial growth factor immunoreactivity was detected in bilateral cortex, but ipsilateral cortex staining intensity and numbers were greater than the contralateral cortex. Vascular endothelial growth factor immunoreactive cells were easily found along the peri-infarct area 12 hours after focal cerebral ischemia. The expression of nestin increased throughout the microvasculature in the ischemic core and the peri-infarct area in all experimental rats after 24 hours of ischemic injury. Nestin immunoreactivity increased in the subventricular zone during 12 hours to 3 days, and prominently increased in the ipsilateral cortex between 3–7 days. Nestin-labeled cells showed dual differentiation with microvessels near the infarct core and reactive astrocytes in the peri-infarct area. BrdU-labeled cells were increased gradually from day 1 in the ipsilateral subventricular zone and cortex, and numerous BrdU-labeled cells were observed in the peri-infarct area and non-lesioned cortex at 3 days. BrdU-labeled cells rather than neurons, were mainly co-labeled with nestin and GFAP. Early expressions of hypoxia-inducible factor-1α and vascular endothelial growth factor after ischemia made 展开更多
AIM： To investigate the usefulness of tumor markers and adenosine deaminase in differentiating between tuberculous peritonitis （TBP） and peritoneal carcinoma- tosis （PC）. METHODS： A retrospective analysis of dat...AIM： To investigate the usefulness of tumor markers and adenosine deaminase in differentiating between tuberculous peritonitis （TBP） and peritoneal carcinoma- tosis （PC）. METHODS： A retrospective analysis of data was per- formed on consecutive patients who underwent perito- neoscopic and abdominal computed tomography （CT） evaluations. Among 75 patients at the Seoul National University Hospital from January 2000 to June 2010 who underwent both tests, 27 patients （36.0%） and 25 patients （33.3%） were diagnosed with TBP and PC, re- spectively. Diagnosis was confirmed by peritoneoscopic biopsy. RESULTS： Serum c-reactive protein （7.88：1：6.62 mg/ dL vs 3.12 ＋ 2.69 mg/dL, P = 0.01）, ascites adenos- ine deaminase （66.76：1：32.09 IU/L vs 13.89 ：l： 8.95 IU/L, P 〈 0.01）, ascites lymphocyte proportion （67.77 ：1： 23.41% vs 48.36 ＋ 18.78%, P 〈 0.01）, and serum- ascites albumin gradient （0.72 ＋ 0.49 g/dL vs 1.05 ＋ 0.50 g/dL, P = 0.03） were significantly different be- tween the two groups. Among tumor markers, serum and ascites carcinoembryonic antigen, serum carbohy- drate antigen 19-9 showed significant difference be- tween two groups. Abdominal CT examinations showed that smooth involvement of the parietal peritoneum was more common in the TBP group （77.8% vs 40.7%） whereas nodular involvement was more common in the PC group （14.8% vs 40.7%, P = 0.04）. From receiver operating characteristic （ROC） curves ascites adeno- sines deaminase （ADA） showed better discriminative capability than tumor markers. An ADA cut-off level of 21 IU/L was found to yield the best results of differ- ential diagnosis; sensitivity, specificity, positive predic- tive value, and negative predictive value were 92.0%, 85.0%, 88.5% and 89.5%, respectively. CONCLUSION： Besides clinical and radiologic findings, ascitic fluid ADA measurement is helpful in the differen- tial diagnosis of TBP and PC.展开更多
AIM： To investigate the effect of Patrinia scabiosaefolia （PS） on the cholecystokinin （CCK） octapeptide-induced acute pancreatitis （AP） in rats.METHODS： Wistar rats weighing 240-260 g were divided into three g...AIM： To investigate the effect of Patrinia scabiosaefolia （PS） on the cholecystokinin （CCK） octapeptide-induced acute pancreatitis （AP） in rats.METHODS： Wistar rats weighing 240-260 g were divided into three groups： （1） Normal saline-treated group; （2） treatment with PS at 100 mg/kg group, in which PS was administered orally, followed by subcutaneous administration of 75μg/kg CCK octapeptide three times after 1, 3 and 5 h, and this whole procedure was repeated for 5 d; （3） treatment with saline group, in which the protocols were the same as in treatment group with PS. We determined the pancreatic weight/ body weight ratio, the levels of pancreatic HSP60, HSP72 and the secretion of pro-inflammatory cytokines. Repeated CCK octapeptide treatment resulted in the typical laboratory findings of experimentally induced pancreatitis.RESULTS： PS reduced the pancreatic weight/body weight ratio, the levels of serum amylase and lipase, and inhibited expressions of pro-inflammatory cytokines in the CCK octapeptide-induced AP. Furthermore, PS pretreatment increased the pancreatic levels of HSP60 and HSP72.CONCLUSION： Pretreatment with PS has an antiiinflammatory effect on CCK octapeptide-induced AP.展开更多
AIM: To investigate whether adding ecabet sodium to the standard triple therapy for H pylori infection improve eradication rate. METHODS: Two hundred and fifty-seven H pylori-infected patients were randomly assigned t...AIM: To investigate whether adding ecabet sodium to the standard triple therapy for H pylori infection improve eradication rate. METHODS: Two hundred and fifty-seven H pylori-infected patients were randomly assigned to standard triple therapy (group A, n = 129) or triple therapy plus ecabet sodium (group B, n = 128). Successful eradication was defined as a negative 13C-urea breath test 6-8 wk after completion of treatment. RESULTS: After completion of therapy, 194/257 patients showed negative 13C-urea breath test results. According to intention-to-treat analysis, the infection was eradicated in 93/129 (72.1%) patients in group A and 101/128 (78.9%) in group B (P = 0.204). Per-protocol analysis showed successful eradication in 93/118 (78.8%) patients from group A and 101/114 (88.6%) from group B (P = 0.044). There were no significant differences in the side effects experienced by the patients in the two treatment groups. CONCLUSION: Our results suggest that the addition of ecabet sodium improves the efficacy of the standard triple therapy for H pylori.展开更多
AIM： To investigate the effect of selective Cyclooxygenase-2 （COX-2） inhibitor 4-[5-（4-Chloro-phenyl）-3- （trifluoromethyl）- 1H-pyrazol- 1-yl] benzenesulfonamide （SC-236）, on the cholecystokinin （CCK）-octape...AIM： To investigate the effect of selective Cyclooxygenase-2 （COX-2） inhibitor 4-[5-（4-Chloro-phenyl）-3- （trifluoromethyl）- 1H-pyrazol- 1-yl] benzenesulfonamide （SC-236）, on the cholecystokinin （CCK）-octapeptideinduced acute pancreatitis （AP） in rats. METHODS： Wistar rat weighing 240 g to 260 g were divided into three groups. （1） Normal DMSO treated group, （2） SC-236 at 4 mg/kg treated group; SC-236 systemically administered via the intravenous （i.v.） catheter, followed by 75 μg/kg CCK octapeptide subcutaneously three times, after 1, 3 and 5 h. This whole procedure was repeated for 5 d. （3） Dimethyl sulfoxide （DMSO） treated group： an identical protocol was used in this group as in the SC-236 cohort （see 2. above）. Repeated CCK octapeptide treatment resulted in a typical experimentally induced pancreatitis in the Wistar rats. RESULTS： SC-236 improved the severity of CCK- octapeptide-induced AP as measured by laboratory criteria [the pancreatic weight/body weight （p.w/ b.w） ratio, the level of serum amylase and lipase]. The SC-236 treated group showed minimal histologic evidence of pancreatitis and a significant reduction in myeloperoxidase activity. SC-236 also increased heat shock protein （HSP）-60 and HSP72 compared with the DMSO-treated group in the CCK-octapeptide-induced AP and also reduced the pancreatic levels of COX-2. Furthermore, SC-236 reduced proinflammatory cytokine synthesis and inhibited NF-KB activation compared with the DMSO-treated group in the CCK-octapeptide-induced AP. CONCLUSION： Our results suggested that COX-2 plays pivotal role in the development of AP and COX-2 inhibitors may play a beneficial role in preventing AP.展开更多
AIM To directly compare the efficacy and toxicity of standarddose FOLFIRINOX(sFOLFIRINOX) and modified-dose FOLFIRINOX(mFOLFIRINOX, 75% of standard-dose) for pancreatic cancer.METHODS One hundred and thirty pancreatic...AIM To directly compare the efficacy and toxicity of standarddose FOLFIRINOX(sFOLFIRINOX) and modified-dose FOLFIRINOX(mFOLFIRINOX, 75% of standard-dose) for pancreatic cancer.METHODS One hundred and thirty pancreatic cancer patients who received sFOLFIRINOX(n = 88) or mFOLFIRINOX(n = 42) as their first-line chemotherapy from January 2013 to July 2017 were retrospectively reviewed. For efficacy analysis, the objective response rate(ORR),disease control rate(DCR), progression-free survival(PFS), and overall survival(OS) were evaluated and compared using Pearson's chi-square test, Kaplan-Meier plot and log-rank test. The adverse events(AEs) were evaluated, and severe(≥ grade 3) AEs rates of the two groups were compared for toxicity analysis.RESULTS The mFOLFIRINOX group included more female patients(30.7% vs 57.1%; P = 0.004) and older patients [age(median), 57 vs 63.5; P = 0.018] than the sFOLFIRINOX group. In the efficacy analysis, the ORR and DCR were not significantly different between the two groups(ORR: 39.8% vs 35.7%; P = 0.656; DCR: 80.7% vs 83.3%; P = 0.716). The median PFS and OS were also not different between the groups(PFS: 8.7 mo vs 8.1 mo, P = 0.272; OS: 13.9 mo vs 13.7 mo, P = 0.476). In the safety analysis with severe AEs, the rates of neutropenia(83.0% vs 66.7%; P = 0.044), anorexia(48.9% vs 28.6%; P = 0.029) and diarrhea(13.6% vs 0.0%; P = 0.009) were markedly lower in the mFOLFIRINOX group.CONCLUSION m FOLFIRINOX showed comparable efficacy but better safety compared to sFOLFIRINOX. If clinically necessary, initiating FOLFIRINOX with 75% of the standard-dose can alleviate toxicity concerns without compromising efficacy.展开更多
This study comprises a systematic review and meta-analysis of micmsurgical vasoepididymostomy outcomes in epididymal obstructive azoospermia.A comprehensive literature search was performed using Medline,Embase,and the...This study comprises a systematic review and meta-analysis of micmsurgical vasoepididymostomy outcomes in epididymal obstructive azoospermia.A comprehensive literature search was performed using Medline,Embase,and the Cochrane library that included all studies related to microsurgical vasoepididymostomy.Keywords included “vasoepididymostomy,”“epididymovasostomy,”“epididymal obstruction,”and “epididymis obstruction.”Event rate and risk ratio (RR)were estimated.Patency rate and pregnancy rate were investigated.The analysis comprised 1422 articles,including 42 observational studies with 2298 enrolled patients performed from November 1978 to January 2017.The overall mean patency rate was 64.1%(95%confidence interval [CI]:58.5%-69.3%;F=83.0%),and the overall mean pregnancy rate was 31.1%(95%CI:26.9%-35.7%;I^2=73.0%).We performed a meta-analysis comparing the patency rate of bilateral microsurgical vasoepididymostomy and unilateral microsurgical vasoepididymostomy and found an RR of 1.38%(95%CI: 1.21%-1.57%;P <0.00001).A comparison of the site of microsurgical vasoepididymostomy showed that caudal or corpus area was favorable for patency rate (RR =1.17%;95%CI: 1.01%-1.35%;P =0.04).Patients with motile sperm in epididymal fluid exhibited an RR of 1.53%(95%CI:1.11%-2.13%;P =0.01)with respect to patency rate. Microsurgical vasoepididymostomy is an effective treatment for epididymal obstructive azoospermia that can improve male fertility. We find that performing microsurgical vasoepididymostomy bilaterally,anastomosing a larger caudal area,and containing motile sperm in epididymis fluid can potentially achieve a superior patency rate.展开更多
Allium is a complicated genus that includes approximately 1000 species.Although its morphology is well studied,the taxonomic importance of many morphological traits,including floral traits,are poorly understood.Here,w...Allium is a complicated genus that includes approximately 1000 species.Although its morphology is well studied,the taxonomic importance of many morphological traits,including floral traits,are poorly understood.Here,we examined and measured the floral characteristics of 87 accessions of 74 Allium taxa(belonging to 30 sections and nine subgenera)from Central to Eastern Asian countries.We then examined the taxonomic relationships between select flower characteristics and a phylogenetic tree based on ITS sequences.Our results confirm that floral morphology provides key taxonomic information to assess species delimitation in Allium.We found that perianth color is an important characteristic within the subg.Melanocrommyum,Polyprason,and Reticulatobulbosa.In subg.Allium,Cepa,and Rhizirideum,significant characteristics include ovary shape,perianth shape,and inner tepal apex.For species in subg.Angunium,the key taxonomic character is ovule number(only one ovule in per locule).In the subg.Allium,Cepa,Polyprason,and Reticulatobulbosa,which belong to the third evolutionary line of Allium,hood-like appendages occur in the ovary,although these do not occur in subg.Rhizirideum.Our results also indicated that the flower morphology of several species in some sections are not clearly distinguished,e.g.,sect.Sacculiferum(subg.Cepa)and sect.Tenuissima(subg.Rhizirideum).This study provides detailed photographs and descriptions of floral characteristics and information on general distributions,habitats,and phenology of the studied taxa.展开更多
Elevating the charge cut-off voltage beyond traditional 4.2 V is a commonly accepted technology to increase the energy density of Li-ion batteries(LIBs) but the risk of Li-dendrites and fire hazard increases as well. ...Elevating the charge cut-off voltage beyond traditional 4.2 V is a commonly accepted technology to increase the energy density of Li-ion batteries(LIBs) but the risk of Li-dendrites and fire hazard increases as well. The use of ambi-functional additive, which forms stable solid electrolyte interphase(SEI) simultaneously at both cathode and anode, is a key to enabling a dendrites-free and well-working high-voltage LIB. Herein, a novel ambi-functional additive, pentaerythritol disulfate(PEDS), at 1 wt% without any other additive is demonstrated. We show the feasibility and high impacts of PEDS in forming lithium sulfateincorporated robust SEI layers at NCM523 cathode and graphite anode in 1 Ah-level pouch cell under4.4 V, 25 °C and 0.1 C rate, which mitigates the high-voltage instability, metal-dissolution and cracks on NCM523 particles, and prevents Li-dendrites at graphite anode. Improved capacity retention of 83%after 300 cycles is thereby achieved, with respect to 69% with base electrolyte, offering a promising path toward the design of practical high-energy LIBs.展开更多
Incorporation of higher content Si anode material beyond 5 wt% to Li-ion batteries(LIBs)is challenging,owing to large volume change,swelling,and solid electrolyte interphase(SEI)instability issues.Herein,a strategy of...Incorporation of higher content Si anode material beyond 5 wt% to Li-ion batteries(LIBs)is challenging,owing to large volume change,swelling,and solid electrolyte interphase(SEI)instability issues.Herein,a strategy of diacetoxydimethylsilane(DAMS)additive-directed SEI stabilization is proposed for a stable operation of Si-0.33FeSi_(2)(named as Si-Fe)anode without graphite,which provides siloxane inorganics and organics enrichment that compensate insufficient passivation of fluoroethylene carbonate(FEC)additive and reduce a dependence on FEC.Unprecedented stable cycling performance of highly loaded(3.5 mA h cm^(-2))pure Si-Fe anode is achieved with 2 wt%DAMS combined with 9 wt%FEC additives under ambient pressure,yielding high capacity 1270 mA h g^(-1)at 0.5 C and significantly improved capacity retention of 81% after 100 cycles,whereas short circuit and rapid capacity fade occur with FEC only additive.DAMS-directed robust SEI layer dramatically suppresses swelling and particles crossover through separator,and therefore prevents short circuit,demonstrating a possible operation of pure Si or Sidominant anodes in the next-generation high-energy-density and safe LIBs.展开更多
OBJECTIVE: To define the effects of Xanthoceras sorbifolia(EXS) on vascular inflammation and the mechanisms in endothelial cells.METHODS: Vascular protective effects of an ethanol extract of seeds from EXS(1-50 μg/mL...OBJECTIVE: To define the effects of Xanthoceras sorbifolia(EXS) on vascular inflammation and the mechanisms in endothelial cells.METHODS: Vascular protective effects of an ethanol extract of seeds from EXS(1-50 μg/mL) against tumor necrosis factor-α(TNF-α)-induced vascularinflammation were examined in human umbilical vein endothelial cells(HUVECs).RESULTS: EXS significantly decreased TNF-α-induced expression of cell adhesion molecules, such as intracellular adhesion molecule-1, vascular cell adhesion molecule-1, and endothelial cell selectin,in a dose-dependent manner. Pre-treatment with EXS significantly inhibited translocation and transcriptional activity of nuclear factor-κB(NF-κB) increased by TNF-α. EXS also significantly inhibited formation of intracellular reactive oxygen species(ROS). Moreover, the vascular protective effects of EXS were linked to up-regulation of heme oxygenase-1(HO-1) and nuclear factor E2-related factor-2(Nrf-2) expression. EXS-induced HO-1 expression was significantly decreased in SnPP(HO-1 inhibitor)-and HO-1 siRNA-treated cells, whereas an increase was found in cobalt protoporphyrin IX(CoPP)(HO-1 inducer)-treated cells. In addition, pretreatment with EXS increased HO-1 and Nrf-2 expression under TNF-α stimulation with or without N-acetyl-L-cysteine. Furthermore, the inhibitory effects of EXS on TNF-α-induced vascular inflammation were partially reversed in SnPP-and of HO-1siRNA-treated cells but increased by CoPP.CONCLUSION: These results suggest that EXS may have important implications for prevention of vascular complications associated with vascular inflammation by inhibition of the NF-κB/ROS pathway and activation of the Nrf-2/HO-1 pathway.展开更多
Background:Although several prediction models for the occurrence of postoperative pancreatic fistula(POPF)after pancreatoduodenectomy(PD)exist,all were established using Western cohorts.Large-scale external validation...Background:Although several prediction models for the occurrence of postoperative pancreatic fistula(POPF)after pancreatoduodenectomy(PD)exist,all were established using Western cohorts.Large-scale external validation studies in Eastern cohorts that consider demographic variables including lower body mass index(BMI)are scarce.The purpose of this study was to externally validate POPF prediction models using nationwide large-scale Korean cohorts.Methods:Nine tertiary university hospitals in the Republic of Korea participated.Patients'preoperative characteristics,intraoperative factors,and pathologic findings were evaluated.POPF grades were determined according to the 2016 International Study Group on Pancreatic Surgery definition.Three POPF risk models(Callery,Roberts,and Mungroop)were selected for external validation.Results:A total of 1,898 PD patients were enrolled.A non-pancreatic disease diagnosis[hazard ratio(HR),1.856;95%confidence interval(CI),1.223–2.817;P=0.004),higher preoperative BMI(HR,1.069;95%CI,1.019–1.121;P=0.006),and soft pancreatic texture(HR,1.859;95%CI,1.264–2.735;P=0.002)were independent risk factors for clinically relevant POPF(CR-POPF).The area under the receiver operating characteristic curve(AUC)values were 0.61,0.64,and 0.63 on the Callery,Roberts,and Mungroop models,respectively;all were lower than those published in each external validation study.Conclusions:Western POPF prediction models performed less well when applied to Korean cohorts.Thus,a large-scale Eastern-specific and externally validated POPF prediction model is needed.展开更多
AIM: To analyze the expression profiles of premalignant and/or preclinical lesions of gastric cancers.METHODS: We analyzed the expression profiles of normal gastric pit, tubular adenoma and carcinoma in situ using mic...AIM: To analyze the expression profiles of premalignant and/or preclinical lesions of gastric cancers.METHODS: We analyzed the expression profiles of normal gastric pit, tubular adenoma and carcinoma in situ using microdissected cells from routine gastric biopsies. For the DNA microarray analysis of formalin-fixed samples,we developed a simple and reproducible RNA extraction and linear amplification procedure applying two polymerasebinding sites. The amplification procedure took only 8 h and yielded comparable DNA microarray data between formalin-fixed tissues and unfixed controls.RESULTS: In comparison with normal pit, adenoma/carcinoma showed 504 up-regulated and 29 down-regulated genes at the expected false significance rate 0.15%. The differential expression between adenoma and carcinoma in situ was subtle: 50 and 22 genes were up-, and down-regulated in carcinomas at the expected false significance rate of 0.61%, respectively. Differentially expressed genes were grouped according to patterns of the sequential changes for the 'tendency analysis' in the gastric mucosaadenoma-carcinoma sequence.CONCLUSION: Groups of genes are shown to reflect the sequential expression changes in the early carcinogenic steps of stomach cancer. It is suggested that molecular carcinogenic pathways could be analyzed using routinely processed biopsies.展开更多
BACKGROUND Although the criteria for the indication of endoscopic submucosal dissection(ESD)for undifferentiated early gastric cancer(UD-EGC)have been recently proposed,accumulating reports on the non-negligible rate ...BACKGROUND Although the criteria for the indication of endoscopic submucosal dissection(ESD)for undifferentiated early gastric cancer(UD-EGC)have been recently proposed,accumulating reports on the non-negligible rate of lymph node metastasis(LNM)after indicated ESD raise questions on the reliability of the current criteria.AIM To investigate the prevalence and risk factors of LNM in UD-EGC cases meeting the expanded indication for ESD.METHODS We retrospectively reviewed 4780 UD-EGC cases that underwent surgical resection between January 2008 and February 2019 at Asan Medical Center,a tertiary university hospital in Korea.To identify the risk factors of LNM of UDEGC meeting the expanded criteria for ESD,we performed a case-control study by matching the cases with LNM to those without at a ratio of 1:4.We reviewed the clinical,endoscopic,and histologic features of the cases to identify features with a significant difference according to the presence of LNM.Univariate and multivariate logistic regression analyses were performed to estimate the odds ratios(ORs).RESULTS Of the 4780 UD-EGC cases,1240(25.9%)were identified to meet the expanded indication for ESD.Of the 1240 cases,14(1.1%)cases had LNM.Among the various clinical,endoscopic,and histopathological features that were evaluated,mixed histology(tumors consisting of 10%-90%of signet ring cells)had a marginally significant association(P=0.059)with the risk of LNM.Moreover,diffuse blurring of the muscularis mucosae(MM)underneath the tumorous epithelium,a previously unrecognized histologic feature,had a significant association with the absence of LNM(P=0.028).Multivariate logistic regression analysis showed that the blurring of MM was the only explanatory variable significantly associated with a reduced risk of LNM(OR:0.12,95%CI:0.02-0.95;P=0.045).CONCLUSION The risk of LNM is higher than expected when using the current expanded indication for UDEGC.Histological evaluation could provide useful clues for reducing the risk of LNM.展开更多
Objective:While a rushed operation can omit essential procedures,prolonged operative time results in higher morbidity.Nevertheless,the optimal operative time range remains uncertain.This study aimed to estimate the id...Objective:While a rushed operation can omit essential procedures,prolonged operative time results in higher morbidity.Nevertheless,the optimal operative time range remains uncertain.This study aimed to estimate the ideal operative time range and evaluate its applicability in laparoscopic cancer surgery.Methods:A prospectively collected multicenter database of 397 patients who underwent laparoscopic distal gastrectomy were retrospectively reviewed.The ideal operative time range was statistically calculated by separately analyzing the operative time of uneventful surgeries.Finally,intraoperative and postoperative outcomes were compared among the shorter,ideal,and longer operative time groups.Results:The statistically calculated ideal operative time was 135.4-165.4 min.The longer operative time(LOT)group had a lower rate of uneventful,perfect surgery than the ideal or shorter operative time(IOT/SOT)group(2.8%vs.8.8%and 2.2%vs.13.4%,all P<0.05).Longer operative time increased bleeding,postoperative morbidities,and delayed diet and discharge(all P<0.05).Particularly,an uneventful,perfect surgery could not be achieved when the operative time exceeded 240 min.Regardless of ideal time range,SOT group achieved the highest percentage of uneventful surgery(13.4%),which was possible by surgeon's ability to retrieve a higher number of lymph nodes and perform≥150 gastrectomies annually.Conclusions:Operative time longer than the ideal time range(especially≥240 min)should be avoided.If the essential operative procedure were faithfully conducted without compromising oncological safety,an operative time shorter than the ideal range leaded to a better prognosis.Efforts to minimize operative time should be attempted with sufficient surgical experience.展开更多
Fas-associated factor 1 (FAF1) is a scaffolding protein that plays multiple functions, and dysregulation of FAF1 is associated withmany types of diseases such as cancers. FAF1 contains multiple ubiquitin-related domai...Fas-associated factor 1 (FAF1) is a scaffolding protein that plays multiple functions, and dysregulation of FAF1 is associated withmany types of diseases such as cancers. FAF1 contains multiple ubiquitin-related domains (UBA, UBL1, UBL2, UAS, and UBX), eachdomain interacting with a specific partner. In particular, the interaction of UBL1 with heat shock protein 70 (Hsp70) is associatedwith tumor formation, although the molecular understanding remains unknown. In this study, the structural analysis revealed thatHis160 of FAF1 is important for its interaction with Hsp70. The association of Hsp70 with FAF1 is required for the interaction withIQGAP1. FAF1 negatively regulates RhoA activation by FAF1–Hsp70 complex formation, which then interacts with IQGAP1. Thesesteps play a key role in maintaining the stability of cell-to-cell junction. We conclude that FAF1 plays a critical role in the structureand function of adherens junction during tissue homeostasis and morphogenesis by suppressing RhoA activation, which induces theactivation of Rho-associated protein kinase, phosphorylation of myosin light chain, formation of actin stress fiber, and disruptionof adherens junction. In addition, depletion of FAF1 increased collective invasion in a 3D spheroid cell culture. These results provideinsightinto how the FAF1–Hsp70 complex acts as a novelregulator ofthe adherens junction integrity. The complex can be a potentialtherapeutic target to inhibit tumorigenesis and metastasis.展开更多
文摘To clarify the role of neoadjuvant concurrent chemoradiotherapy (NACCRT) followed by surgical resection for localized or locally advanced perihilar cholangiocarcinoma (CCA).METHODSWe retrospectively reviewed 57 patients who underwent surgical resection with or without NACCRT for perihilar CCA; 12 patients received NACCRT and 45 patients did not received NACCRT. Patients with locally advanced perihilar CCA requiring NACCRT were defined as follows: (1) a mass involving unilateral branches of the portal vein or hepatic artery with insufficient volume of the anticipated remnant lobe; or (2) an infiltrating mass in the main portal vein that was too long for reconstruction, identified at preoperative staging.RESULTSThe median disease-free survival (DFS) durations of the neoadjuvant and non-neoadjuvant CCRT groups were 26.0 and 15.1 mo, respectively (P = 0.91). The median overall survival (OS) durations of the neoadjuvant and non-neoadjuvant CCRT groups were 32.9 and 27.1 mo, respectively (P = 0.26). The NACCRT group showed a downstaging tendency compared to the non-NACCRT group as compared with the tumor stage confirmed by histological examination after surgery and the tumor stage confirmed by imaging test at the time of diagnosis (P = 0.01).CONCLUSIONNACCRT does not prolong DFS and OS in localized or locally advanced perihilar CCA. However, NACCRT may allow tumor downstaging and improve tumor resectability.
文摘AIM:The generation of oxygen free radicals has been implicated in the pathogenesis of experimental pancreatitis. The aim of this study was to determine the role of oxygen free radicals in patients with acute pancreatitis. METHODS:The plasma levels of C-reactive protein(CRP), lipid peroxide(LPO),myeloperoxidase(MPO)and superoxide dismutase(SOD)were measured in 13 patients with acute pancreatitis and 14 healthy volunteers. RESULTS:Among the patients with acute pancreatitis,there were higher plasma levels of LPO and MPO and lower SOD activity in patients with severe pancreatitis than in those with mild pancreatitis.However,there was no significant difference in the serum marker of oxidative stress no matter what the etiology was.The LPO level was especially correlated with the concentration of serum CRP and CT severity index. CONCLUSION:The oxygen free radicals may be closely associated with inflammatory process and the severity of acute pancreatitis.Especially,the concentration of plasma LPO is a meaningful index for determining the severity of the disease.
基金supported by the National Research Foundation of Korea Grant funded by the Korean Government,No.NRF-013-2011-1-E00045
文摘Endogenous neural stem cells become ＂activated＂ after neuronal injury, but the activation sequence and fate of endogenous neural stem cells in focal cerebral ischemia model are little known. We evaluated the relationships between neural stem cells and hypoxia-inducible factor-1α and vascular endothelial growth factor expression in a photothromobotic rat stroke model using immunohistochemistry and western blot analysis. We also evaluated the chronological changes of neural stem cells by 5-bromo-2′-deoxyuridine（BrdU） incorporation. Hypoxia-inducible factor-1α expression was initially increased from 1 hour after ischemic injury, followed by vascular endothelial growth factor expression. Hypoxia-inducible factor-1α immunoreactivity was detected in the ipsilateral cortical neurons of the infarct core and peri-infarct area. Vascular endothelial growth factor immunoreactivity was detected in bilateral cortex, but ipsilateral cortex staining intensity and numbers were greater than the contralateral cortex. Vascular endothelial growth factor immunoreactive cells were easily found along the peri-infarct area 12 hours after focal cerebral ischemia. The expression of nestin increased throughout the microvasculature in the ischemic core and the peri-infarct area in all experimental rats after 24 hours of ischemic injury. Nestin immunoreactivity increased in the subventricular zone during 12 hours to 3 days, and prominently increased in the ipsilateral cortex between 3–7 days. Nestin-labeled cells showed dual differentiation with microvessels near the infarct core and reactive astrocytes in the peri-infarct area. BrdU-labeled cells were increased gradually from day 1 in the ipsilateral subventricular zone and cortex, and numerous BrdU-labeled cells were observed in the peri-infarct area and non-lesioned cortex at 3 days. BrdU-labeled cells rather than neurons, were mainly co-labeled with nestin and GFAP. Early expressions of hypoxia-inducible factor-1α and vascular endothelial growth factor after ischemia made
文摘AIM： To investigate the usefulness of tumor markers and adenosine deaminase in differentiating between tuberculous peritonitis （TBP） and peritoneal carcinoma- tosis （PC）. METHODS： A retrospective analysis of data was per- formed on consecutive patients who underwent perito- neoscopic and abdominal computed tomography （CT） evaluations. Among 75 patients at the Seoul National University Hospital from January 2000 to June 2010 who underwent both tests, 27 patients （36.0%） and 25 patients （33.3%） were diagnosed with TBP and PC, re- spectively. Diagnosis was confirmed by peritoneoscopic biopsy. RESULTS： Serum c-reactive protein （7.88：1：6.62 mg/ dL vs 3.12 ＋ 2.69 mg/dL, P = 0.01）, ascites adenos- ine deaminase （66.76：1：32.09 IU/L vs 13.89 ：l： 8.95 IU/L, P 〈 0.01）, ascites lymphocyte proportion （67.77 ：1： 23.41% vs 48.36 ＋ 18.78%, P 〈 0.01）, and serum- ascites albumin gradient （0.72 ＋ 0.49 g/dL vs 1.05 ＋ 0.50 g/dL, P = 0.03） were significantly different be- tween the two groups. Among tumor markers, serum and ascites carcinoembryonic antigen, serum carbohy- drate antigen 19-9 showed significant difference be- tween two groups. Abdominal CT examinations showed that smooth involvement of the parietal peritoneum was more common in the TBP group （77.8% vs 40.7%） whereas nodular involvement was more common in the PC group （14.8% vs 40.7%, P = 0.04）. From receiver operating characteristic （ROC） curves ascites adeno- sines deaminase （ADA） showed better discriminative capability than tumor markers. An ADA cut-off level of 21 IU/L was found to yield the best results of differ- ential diagnosis; sensitivity, specificity, positive predic- tive value, and negative predictive value were 92.0%, 85.0%, 88.5% and 89.5%, respectively. CONCLUSION： Besides clinical and radiologic findings, ascitic fluid ADA measurement is helpful in the differen- tial diagnosis of TBP and PC.
文摘AIM： To investigate the effect of Patrinia scabiosaefolia （PS） on the cholecystokinin （CCK） octapeptide-induced acute pancreatitis （AP） in rats.METHODS： Wistar rats weighing 240-260 g were divided into three groups： （1） Normal saline-treated group; （2） treatment with PS at 100 mg/kg group, in which PS was administered orally, followed by subcutaneous administration of 75μg/kg CCK octapeptide three times after 1, 3 and 5 h, and this whole procedure was repeated for 5 d; （3） treatment with saline group, in which the protocols were the same as in treatment group with PS. We determined the pancreatic weight/ body weight ratio, the levels of pancreatic HSP60, HSP72 and the secretion of pro-inflammatory cytokines. Repeated CCK octapeptide treatment resulted in the typical laboratory findings of experimentally induced pancreatitis.RESULTS： PS reduced the pancreatic weight/body weight ratio, the levels of serum amylase and lipase, and inhibited expressions of pro-inflammatory cytokines in the CCK octapeptide-induced AP. Furthermore, PS pretreatment increased the pancreatic levels of HSP60 and HSP72.CONCLUSION： Pretreatment with PS has an antiiinflammatory effect on CCK octapeptide-induced AP.
基金An unrestricted grant by JEIL Pharm.Co.,Ltd.,Korea
文摘AIM: To investigate whether adding ecabet sodium to the standard triple therapy for H pylori infection improve eradication rate. METHODS: Two hundred and fifty-seven H pylori-infected patients were randomly assigned to standard triple therapy (group A, n = 129) or triple therapy plus ecabet sodium (group B, n = 128). Successful eradication was defined as a negative 13C-urea breath test 6-8 wk after completion of treatment. RESULTS: After completion of therapy, 194/257 patients showed negative 13C-urea breath test results. According to intention-to-treat analysis, the infection was eradicated in 93/129 (72.1%) patients in group A and 101/128 (78.9%) in group B (P = 0.204). Per-protocol analysis showed successful eradication in 93/118 (78.8%) patients from group A and 101/114 (88.6%) from group B (P = 0.044). There were no significant differences in the side effects experienced by the patients in the two treatment groups. CONCLUSION: Our results suggest that the addition of ecabet sodium improves the efficacy of the standard triple therapy for H pylori.
基金Supported by the Ministry of Science & Technology/Korea Science & Engineering Foundation through the Vestibuloco-chlear Research Center at Wonkwang University, No. R13-2002- 055-00000-0
文摘AIM： To investigate the effect of selective Cyclooxygenase-2 （COX-2） inhibitor 4-[5-（4-Chloro-phenyl）-3- （trifluoromethyl）- 1H-pyrazol- 1-yl] benzenesulfonamide （SC-236）, on the cholecystokinin （CCK）-octapeptideinduced acute pancreatitis （AP） in rats. METHODS： Wistar rat weighing 240 g to 260 g were divided into three groups. （1） Normal DMSO treated group, （2） SC-236 at 4 mg/kg treated group; SC-236 systemically administered via the intravenous （i.v.） catheter, followed by 75 μg/kg CCK octapeptide subcutaneously three times, after 1, 3 and 5 h. This whole procedure was repeated for 5 d. （3） Dimethyl sulfoxide （DMSO） treated group： an identical protocol was used in this group as in the SC-236 cohort （see 2. above）. Repeated CCK octapeptide treatment resulted in a typical experimentally induced pancreatitis in the Wistar rats. RESULTS： SC-236 improved the severity of CCK- octapeptide-induced AP as measured by laboratory criteria [the pancreatic weight/body weight （p.w/ b.w） ratio, the level of serum amylase and lipase]. The SC-236 treated group showed minimal histologic evidence of pancreatitis and a significant reduction in myeloperoxidase activity. SC-236 also increased heat shock protein （HSP）-60 and HSP72 compared with the DMSO-treated group in the CCK-octapeptide-induced AP and also reduced the pancreatic levels of COX-2. Furthermore, SC-236 reduced proinflammatory cytokine synthesis and inhibited NF-KB activation compared with the DMSO-treated group in the CCK-octapeptide-induced AP. CONCLUSION： Our results suggested that COX-2 plays pivotal role in the development of AP and COX-2 inhibitors may play a beneficial role in preventing AP.
文摘AIM To directly compare the efficacy and toxicity of standarddose FOLFIRINOX(sFOLFIRINOX) and modified-dose FOLFIRINOX(mFOLFIRINOX, 75% of standard-dose) for pancreatic cancer.METHODS One hundred and thirty pancreatic cancer patients who received sFOLFIRINOX(n = 88) or mFOLFIRINOX(n = 42) as their first-line chemotherapy from January 2013 to July 2017 were retrospectively reviewed. For efficacy analysis, the objective response rate(ORR),disease control rate(DCR), progression-free survival(PFS), and overall survival(OS) were evaluated and compared using Pearson's chi-square test, Kaplan-Meier plot and log-rank test. The adverse events(AEs) were evaluated, and severe(≥ grade 3) AEs rates of the two groups were compared for toxicity analysis.RESULTS The mFOLFIRINOX group included more female patients(30.7% vs 57.1%; P = 0.004) and older patients [age(median), 57 vs 63.5; P = 0.018] than the sFOLFIRINOX group. In the efficacy analysis, the ORR and DCR were not significantly different between the two groups(ORR: 39.8% vs 35.7%; P = 0.656; DCR: 80.7% vs 83.3%; P = 0.716). The median PFS and OS were also not different between the groups(PFS: 8.7 mo vs 8.1 mo, P = 0.272; OS: 13.9 mo vs 13.7 mo, P = 0.476). In the safety analysis with severe AEs, the rates of neutropenia(83.0% vs 66.7%; P = 0.044), anorexia(48.9% vs 28.6%; P = 0.029) and diarrhea(13.6% vs 0.0%; P = 0.009) were markedly lower in the mFOLFIRINOX group.CONCLUSION m FOLFIRINOX showed comparable efficacy but better safety compared to sFOLFIRINOX. If clinically necessary, initiating FOLFIRINOX with 75% of the standard-dose can alleviate toxicity concerns without compromising efficacy.
文摘This study comprises a systematic review and meta-analysis of micmsurgical vasoepididymostomy outcomes in epididymal obstructive azoospermia.A comprehensive literature search was performed using Medline,Embase,and the Cochrane library that included all studies related to microsurgical vasoepididymostomy.Keywords included “vasoepididymostomy,”“epididymovasostomy,”“epididymal obstruction,”and “epididymis obstruction.”Event rate and risk ratio (RR)were estimated.Patency rate and pregnancy rate were investigated.The analysis comprised 1422 articles,including 42 observational studies with 2298 enrolled patients performed from November 1978 to January 2017.The overall mean patency rate was 64.1%(95%confidence interval [CI]:58.5%-69.3%;F=83.0%),and the overall mean pregnancy rate was 31.1%(95%CI:26.9%-35.7%;I^2=73.0%).We performed a meta-analysis comparing the patency rate of bilateral microsurgical vasoepididymostomy and unilateral microsurgical vasoepididymostomy and found an RR of 1.38%(95%CI: 1.21%-1.57%;P <0.00001).A comparison of the site of microsurgical vasoepididymostomy showed that caudal or corpus area was favorable for patency rate (RR =1.17%;95%CI: 1.01%-1.35%;P =0.04).Patients with motile sperm in epididymal fluid exhibited an RR of 1.53%(95%CI:1.11%-2.13%;P =0.01)with respect to patency rate. Microsurgical vasoepididymostomy is an effective treatment for epididymal obstructive azoospermia that can improve male fertility. We find that performing microsurgical vasoepididymostomy bilaterally,anastomosing a larger caudal area,and containing motile sperm in epididymis fluid can potentially achieve a superior patency rate.
基金supported by research grants from the Korea National Arboretum (Grant No. KNA1-1-26, 20-1)the Mid-level professor Financial Program at Changwon National University in 2023
文摘Allium is a complicated genus that includes approximately 1000 species.Although its morphology is well studied,the taxonomic importance of many morphological traits,including floral traits,are poorly understood.Here,we examined and measured the floral characteristics of 87 accessions of 74 Allium taxa(belonging to 30 sections and nine subgenera)from Central to Eastern Asian countries.We then examined the taxonomic relationships between select flower characteristics and a phylogenetic tree based on ITS sequences.Our results confirm that floral morphology provides key taxonomic information to assess species delimitation in Allium.We found that perianth color is an important characteristic within the subg.Melanocrommyum,Polyprason,and Reticulatobulbosa.In subg.Allium,Cepa,and Rhizirideum,significant characteristics include ovary shape,perianth shape,and inner tepal apex.For species in subg.Angunium,the key taxonomic character is ovule number(only one ovule in per locule).In the subg.Allium,Cepa,Polyprason,and Reticulatobulbosa,which belong to the third evolutionary line of Allium,hood-like appendages occur in the ovary,although these do not occur in subg.Rhizirideum.Our results also indicated that the flower morphology of several species in some sections are not clearly distinguished,e.g.,sect.Sacculiferum(subg.Cepa)and sect.Tenuissima(subg.Rhizirideum).This study provides detailed photographs and descriptions of floral characteristics and information on general distributions,habitats,and phenology of the studied taxa.
基金supported by the Ministry of Trade,Industry&Energy (A0022-00725)National Research Foundation grant (No.2019R1A2C1084024 and 2021R1A2C2005764) funded by the Ministry of Science and ICT of Korea+2 种基金Chungnam National Universitysupported by the Nano Material Technology Development Program through the National Research Foundation of Koreafunded by the Ministry of Science and ICT of Korea (2009-0082580)。
文摘Elevating the charge cut-off voltage beyond traditional 4.2 V is a commonly accepted technology to increase the energy density of Li-ion batteries(LIBs) but the risk of Li-dendrites and fire hazard increases as well. The use of ambi-functional additive, which forms stable solid electrolyte interphase(SEI) simultaneously at both cathode and anode, is a key to enabling a dendrites-free and well-working high-voltage LIB. Herein, a novel ambi-functional additive, pentaerythritol disulfate(PEDS), at 1 wt% without any other additive is demonstrated. We show the feasibility and high impacts of PEDS in forming lithium sulfateincorporated robust SEI layers at NCM523 cathode and graphite anode in 1 Ah-level pouch cell under4.4 V, 25 °C and 0.1 C rate, which mitigates the high-voltage instability, metal-dissolution and cracks on NCM523 particles, and prevents Li-dendrites at graphite anode. Improved capacity retention of 83%after 300 cycles is thereby achieved, with respect to 69% with base electrolyte, offering a promising path toward the design of practical high-energy LIBs.
基金supported by the National Research Foundation grants funded by the Ministry of Science and ICT of Korea(2021M3H4A3A02086211 and RS-2023-00217581).
文摘Incorporation of higher content Si anode material beyond 5 wt% to Li-ion batteries(LIBs)is challenging,owing to large volume change,swelling,and solid electrolyte interphase(SEI)instability issues.Herein,a strategy of diacetoxydimethylsilane(DAMS)additive-directed SEI stabilization is proposed for a stable operation of Si-0.33FeSi_(2)(named as Si-Fe)anode without graphite,which provides siloxane inorganics and organics enrichment that compensate insufficient passivation of fluoroethylene carbonate(FEC)additive and reduce a dependence on FEC.Unprecedented stable cycling performance of highly loaded(3.5 mA h cm^(-2))pure Si-Fe anode is achieved with 2 wt%DAMS combined with 9 wt%FEC additives under ambient pressure,yielding high capacity 1270 mA h g^(-1)at 0.5 C and significantly improved capacity retention of 81% after 100 cycles,whereas short circuit and rapid capacity fade occur with FEC only additive.DAMS-directed robust SEI layer dramatically suppresses swelling and particles crossover through separator,and therefore prevents short circuit,demonstrating a possible operation of pure Si or Sidominant anodes in the next-generation high-energy-density and safe LIBs.
基金Supported by the Natural Science Foundation of Shandong Province,China(No.ZR2015HM037)a National Research Foundation of Korea(NRF)Grant Funded by the Korean Government(No.NRF-2017R1A5A2015805)
文摘OBJECTIVE: To define the effects of Xanthoceras sorbifolia(EXS) on vascular inflammation and the mechanisms in endothelial cells.METHODS: Vascular protective effects of an ethanol extract of seeds from EXS(1-50 μg/mL) against tumor necrosis factor-α(TNF-α)-induced vascularinflammation were examined in human umbilical vein endothelial cells(HUVECs).RESULTS: EXS significantly decreased TNF-α-induced expression of cell adhesion molecules, such as intracellular adhesion molecule-1, vascular cell adhesion molecule-1, and endothelial cell selectin,in a dose-dependent manner. Pre-treatment with EXS significantly inhibited translocation and transcriptional activity of nuclear factor-κB(NF-κB) increased by TNF-α. EXS also significantly inhibited formation of intracellular reactive oxygen species(ROS). Moreover, the vascular protective effects of EXS were linked to up-regulation of heme oxygenase-1(HO-1) and nuclear factor E2-related factor-2(Nrf-2) expression. EXS-induced HO-1 expression was significantly decreased in SnPP(HO-1 inhibitor)-and HO-1 siRNA-treated cells, whereas an increase was found in cobalt protoporphyrin IX(CoPP)(HO-1 inducer)-treated cells. In addition, pretreatment with EXS increased HO-1 and Nrf-2 expression under TNF-α stimulation with or without N-acetyl-L-cysteine. Furthermore, the inhibitory effects of EXS on TNF-α-induced vascular inflammation were partially reversed in SnPP-and of HO-1siRNA-treated cells but increased by CoPP.CONCLUSION: These results suggest that EXS may have important implications for prevention of vascular complications associated with vascular inflammation by inhibition of the NF-κB/ROS pathway and activation of the Nrf-2/HO-1 pathway.
基金This study was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institutefunded by the Ministry of Health&Welfare,Republic of Korea(grant number:HI16C2037)by the Collaborative Genome Program for Fostering New Post-Genome Industry of the National Research Foundation funded by the Ministry of Science and ICT(NRF-2017M3C9A5031591).
文摘Background:Although several prediction models for the occurrence of postoperative pancreatic fistula(POPF)after pancreatoduodenectomy(PD)exist,all were established using Western cohorts.Large-scale external validation studies in Eastern cohorts that consider demographic variables including lower body mass index(BMI)are scarce.The purpose of this study was to externally validate POPF prediction models using nationwide large-scale Korean cohorts.Methods:Nine tertiary university hospitals in the Republic of Korea participated.Patients'preoperative characteristics,intraoperative factors,and pathologic findings were evaluated.POPF grades were determined according to the 2016 International Study Group on Pancreatic Surgery definition.Three POPF risk models(Callery,Roberts,and Mungroop)were selected for external validation.Results:A total of 1,898 PD patients were enrolled.A non-pancreatic disease diagnosis[hazard ratio(HR),1.856;95%confidence interval(CI),1.223–2.817;P=0.004),higher preoperative BMI(HR,1.069;95%CI,1.019–1.121;P=0.006),and soft pancreatic texture(HR,1.859;95%CI,1.264–2.735;P=0.002)were independent risk factors for clinically relevant POPF(CR-POPF).The area under the receiver operating characteristic curve(AUC)values were 0.61,0.64,and 0.63 on the Callery,Roberts,and Mungroop models,respectively;all were lower than those published in each external validation study.Conclusions:Western POPF prediction models performed less well when applied to Korean cohorts.Thus,a large-scale Eastern-specific and externally validated POPF prediction model is needed.
基金Supported by a Korea Research Foundation Grant, KRF-2003-041-E00052
文摘AIM: To analyze the expression profiles of premalignant and/or preclinical lesions of gastric cancers.METHODS: We analyzed the expression profiles of normal gastric pit, tubular adenoma and carcinoma in situ using microdissected cells from routine gastric biopsies. For the DNA microarray analysis of formalin-fixed samples,we developed a simple and reproducible RNA extraction and linear amplification procedure applying two polymerasebinding sites. The amplification procedure took only 8 h and yielded comparable DNA microarray data between formalin-fixed tissues and unfixed controls.RESULTS: In comparison with normal pit, adenoma/carcinoma showed 504 up-regulated and 29 down-regulated genes at the expected false significance rate 0.15%. The differential expression between adenoma and carcinoma in situ was subtle: 50 and 22 genes were up-, and down-regulated in carcinomas at the expected false significance rate of 0.61%, respectively. Differentially expressed genes were grouped according to patterns of the sequential changes for the 'tendency analysis' in the gastric mucosaadenoma-carcinoma sequence.CONCLUSION: Groups of genes are shown to reflect the sequential expression changes in the early carcinogenic steps of stomach cancer. It is suggested that molecular carcinogenic pathways could be analyzed using routinely processed biopsies.
文摘BACKGROUND Although the criteria for the indication of endoscopic submucosal dissection(ESD)for undifferentiated early gastric cancer(UD-EGC)have been recently proposed,accumulating reports on the non-negligible rate of lymph node metastasis(LNM)after indicated ESD raise questions on the reliability of the current criteria.AIM To investigate the prevalence and risk factors of LNM in UD-EGC cases meeting the expanded indication for ESD.METHODS We retrospectively reviewed 4780 UD-EGC cases that underwent surgical resection between January 2008 and February 2019 at Asan Medical Center,a tertiary university hospital in Korea.To identify the risk factors of LNM of UDEGC meeting the expanded criteria for ESD,we performed a case-control study by matching the cases with LNM to those without at a ratio of 1:4.We reviewed the clinical,endoscopic,and histologic features of the cases to identify features with a significant difference according to the presence of LNM.Univariate and multivariate logistic regression analyses were performed to estimate the odds ratios(ORs).RESULTS Of the 4780 UD-EGC cases,1240(25.9%)were identified to meet the expanded indication for ESD.Of the 1240 cases,14(1.1%)cases had LNM.Among the various clinical,endoscopic,and histopathological features that were evaluated,mixed histology(tumors consisting of 10%-90%of signet ring cells)had a marginally significant association(P=0.059)with the risk of LNM.Moreover,diffuse blurring of the muscularis mucosae(MM)underneath the tumorous epithelium,a previously unrecognized histologic feature,had a significant association with the absence of LNM(P=0.028).Multivariate logistic regression analysis showed that the blurring of MM was the only explanatory variable significantly associated with a reduced risk of LNM(OR:0.12,95%CI:0.02-0.95;P=0.045).CONCLUSION The risk of LNM is higher than expected when using the current expanded indication for UDEGC.Histological evaluation could provide useful clues for reducing the risk of LNM.
文摘Objective:While a rushed operation can omit essential procedures,prolonged operative time results in higher morbidity.Nevertheless,the optimal operative time range remains uncertain.This study aimed to estimate the ideal operative time range and evaluate its applicability in laparoscopic cancer surgery.Methods:A prospectively collected multicenter database of 397 patients who underwent laparoscopic distal gastrectomy were retrospectively reviewed.The ideal operative time range was statistically calculated by separately analyzing the operative time of uneventful surgeries.Finally,intraoperative and postoperative outcomes were compared among the shorter,ideal,and longer operative time groups.Results:The statistically calculated ideal operative time was 135.4-165.4 min.The longer operative time(LOT)group had a lower rate of uneventful,perfect surgery than the ideal or shorter operative time(IOT/SOT)group(2.8%vs.8.8%and 2.2%vs.13.4%,all P<0.05).Longer operative time increased bleeding,postoperative morbidities,and delayed diet and discharge(all P<0.05).Particularly,an uneventful,perfect surgery could not be achieved when the operative time exceeded 240 min.Regardless of ideal time range,SOT group achieved the highest percentage of uneventful surgery(13.4%),which was possible by surgeon's ability to retrieve a higher number of lymph nodes and perform≥150 gastrectomies annually.Conclusions:Operative time longer than the ideal time range(especially≥240 min)should be avoided.If the essential operative procedure were faithfully conducted without compromising oncological safety,an operative time shorter than the ideal range leaded to a better prognosis.Efforts to minimize operative time should be attempted with sufficient surgical experience.
基金Thisworkwas supported by the National Research Foundation of Korea(NRF)grant funded by the Ministry of Science and ICT(2017R1A2B3007224 and 2020R1A4A4079494 to E.E.K.2020R1F1A1055369 to K.-J.L.2019R1A2C2004052 to E.J.S.).S.S.and I.-K.S.were supported by Brain Korea 21 Plus(BK21 Plus)Project.
文摘Fas-associated factor 1 (FAF1) is a scaffolding protein that plays multiple functions, and dysregulation of FAF1 is associated withmany types of diseases such as cancers. FAF1 contains multiple ubiquitin-related domains (UBA, UBL1, UBL2, UAS, and UBX), eachdomain interacting with a specific partner. In particular, the interaction of UBL1 with heat shock protein 70 (Hsp70) is associatedwith tumor formation, although the molecular understanding remains unknown. In this study, the structural analysis revealed thatHis160 of FAF1 is important for its interaction with Hsp70. The association of Hsp70 with FAF1 is required for the interaction withIQGAP1. FAF1 negatively regulates RhoA activation by FAF1–Hsp70 complex formation, which then interacts with IQGAP1. Thesesteps play a key role in maintaining the stability of cell-to-cell junction. We conclude that FAF1 plays a critical role in the structureand function of adherens junction during tissue homeostasis and morphogenesis by suppressing RhoA activation, which induces theactivation of Rho-associated protein kinase, phosphorylation of myosin light chain, formation of actin stress fiber, and disruptionof adherens junction. In addition, depletion of FAF1 increased collective invasion in a 3D spheroid cell culture. These results provideinsightinto how the FAF1–Hsp70 complex acts as a novelregulator ofthe adherens junction integrity. The complex can be a potentialtherapeutic target to inhibit tumorigenesis and metastasis.
