Non-improvement of atrophic gastritis in cases of gastric cancer after successful Helicobacter pylori eradication therapy

BACKGROUND Helicobacter pylori(H.pylori)infection is closely related to the development of gastric cancer(GC).However,GC can develop even after H.pylori eradication.Therefore,it would be extremely useful if GC could be predicted after eradication.The Kyoto classification score for gastritis(GA)is closely related to cancer risk.However,how the score for GC changes after eradication before onset is not well understood.AIM To investigate the characteristics of the progression of Kyoto classification scores for GC after H.pylori eradication.METHODS Eradication of H.pylori was confirmed in all patients using either the urea breath test or the stool antigen test.The Kyoto classification score of GC patients was evaluated by endoscopy at the time of event onset and three years earlier.In ad-dition,the modified atrophy score was evaluated and compared between the GC group and the control GA group.RESULTS In total,30 cases of early GC and 30 cases of chronic GA were evaluated.The pathology of the cancer cases was differentiated adenocarcinoma,except for one case of undifferentiated adenocarcinoma.The total score of the Kyoto classifi-cation was significantly higher in the GC group both at the time of cancer onset and three years earlier(4.97 vs 3.73,P=0.0034;4.2 vs 3.1,P=0.0035,respectively).The modified atrophy score was significantly higher in the GC group both at the time of cancer onset and three years earlier and was significantly improved only in the GA group(5.3 vs 5.3,P=0.5;3.73 vs 3.1,P=0.0475,respectively).CONCLUSION The course of the modified atrophy score is useful for predicting the onset of GC after eradication.Patients with severe atrophy after H.pylori eradication require careful monitoring.

Background diseases and the number of previous intravitreal aflibercept injections on immediate intraocular pressure increase and vitreous reflux rate in phakic eyes

●AIM:To evaluate the effect of background diseases and number of previous intravitreal aflibercept injections(IVAIs)on immediate intraocular pressure(IOP)increase and vitreous reflux(VR)rate and to evaluate the correlation of both age and axial length with immediate IOP increase and VR rate.●METHODS:This study included 105 patients with cystoid macular edema secondary to retinal vein occlusion,35 patients with diabetic macular edema,69 patients with neovascular age-related macular degeneration(nAMD),and 12 patients with myopic choroidal neovascularization,which underwent first-time IVAI.The correlation of immediate IOP increase and VR rates with the four background diseases was investigated.Moreover,the correlation of age with immediate IOP increase and VR rate as well as correlation of axial length with immediate IOP increase and VR rate were evaluated.Further,54 patients with nAMD were treated with IVAI>10 times(multiple IVAIs).Moreover,the correlation of immediate IOP increase and VR rates with first-time and multiple IVAIs in nAMD was determined.●RESULTS:The immediate IOP increase(P=0.16)and VR rates(P=0.50)were almost similar among the four background diseases.The immediate postinjection IOP and age,VR rate and age,immediate postinjection IOP and axial length,or VR rate and axial length were not correlated in the four background diseases.The immediate IOP increase(P=0.66)and VR rates(P=0.28)did not significantly differ between first-time and multiple IVAIs in nAMD.●CONCLUSION:Background diseases and number of previous IVAIs have no effect on immediate IOP increase and VR rate.Further,age and axial length have no correlation on immediate IOP increase and VR rate.

Involvement of Siglec-15 in regulating RAP1/RAC signaling in cytoskeletal remodeling in osteoclasts mediated by macrophage colony-stimulating factor

DNAX-associated protein 12 kD size(DAP12)is a dominant immunoreceptor tyrosine-based activation motif(ITAM)-signaling adaptor that activates costimulatory signals essential for osteoclastogenesis.Although several DAP12-associated receptors(DARs)have been identified in osteoclasts,including triggering receptor expressed on myeloid cells 2(TREM-2),C-type lectin member 5 A(CLEC5A),and sialic acid-binding Ig-like lectin(Siglec)-15,their precise role in the development of osteoclasts and bone remodeling remain poorly understood.In this study,mice deficient in Trem-2,Clec5a,Siglec-15 were generated.

Differential mucin phenotypes and their significance in a variation of colorectal carcinoma

AIM: To investigate mucin expression profiles in colorectal carcinoma (CRC) histological subtypes with regard to clinicopathologic variables and prognosis. METHODS: Mucin (MUC)2 and MUC5AC expressions were assessed by immunohistochemistry for a total of 250 CRC cases that underwent surgical resection. CRCs included 63 well-to-moderately differentiated adenocar-cinomas (WMDAs), 91 poorly differentiated adenocarcinomas (PDAs), 81 mucinous adenocarcinoma (MUAs), and 15 signet-ring cell carcinomas (SRCCs). MUC2 and MUC5AC were scored as positive when ≥ 25% and ≥ 1% of cancer cells were stained positive, respectively. The human mutL homolog 1 and human mutS homolog 2 expressions were assessed by immunohistochemistry in PDAs to investigate mismatch-repair (MMR) status.Tumors that did not express either of these two were considered MMR-deficient. Results were analyzed for associations with clinicopathologic variables and the prognosis in individual histological CRC subtypes. RESULTS: MUC2-positive and MUC5AC-positive WMDA percentages were 49.2% and 30.2%, respectively. In contrast, MUC2-positive and MUC5AC-positive PDA percentages were 9.5% and 51.6%, respectively. MUC2 levels tended to decrease and MUC5AC levels tended to increase from WMDA to PDA. In 21 tumors comprising both adenoma and adenocarcinoma components in a single tumor (4 WMDAs, 7 PDAs, and 10 MUAs), MUC2 was significantly downregulated in PDA and MUC5AC was downregulated in PDA and MUA in the adenoma-carcinoma sequence. These results suggested that MUC2 levels might be associated with malignant potential and that MUC5AC expression was an early event in tumorigenesis. Despite worse prognoses than WMDA, high MUC2 expression levels were maintained in MUA (95.1%) and SRCC (71.5%), which suggested a pathogenesis for these subtypes distinct from that of WMDA. No significant associations were found between MUC2 expression and any clinicopathologic variables in any histological subtype. MUC5AC expression in PDA was closely associated with right-sided location (P = 0.017), absence of nodal metastasis (P = 0.010), low tumor node metastasis stage (P = 0.010), and MMR deficiency (P = 0.003). MUC2 expression in WMDA was a marginal prognostic factor for recurrence/metastasis-free survival (RFS) by univariate Cox analysis (P = 0.077) but not by multivariate Cox analysis (P = 0.161). MUC5AC expression in PDA was a significant prognostic factor for RFS by univariate Cox analysis (P = 0.007) but not by multivariate Cox analysis (P = 0.104). Kaplan-Meier curves and log-rank tests revealed that MUC2 expression was marginally associated with a better WMDA prognosis [P = 0.064 for RFS and P = 0.172 for overall survival (OS)] but not for PDA. In contrast, MUC5AC expression was significantly and marginally associated with a better PDA prognosis in terms of RFS and OS, respectively(P = 0.004 for RFS and P = 0.100 for OS), but not for WMDA and MUA. CONCLUSION: Mucin core protein expression profiles and clinical significance differ according to histological CRC subtypes. This may reflect different pathogeneses for these tumors.

Multi-disciplinary treatment for cholangiocellular carcinoma

Cholangiocarcinoma(CC)is rare malignant tumors composed of cells that resemble those of the biliary tract.It is notoriously difficult to diagnose,and is associated with a high mortality.Traditionally,CC is divided into intrahepatic and extraheaptic disease according to its location within the biliary tree.Intrahepatic cholangiocellular carcinoma(IH-CCC)or peripheral cholangiocellular carcinoma(CCC)appears within the second bifurcation of hepatic bile duct,and is the second most common primary liver cancer following hepatocellular carcinoma(HCC),IH-CCC or peripheral CCC often presents with advanced clinical features,and the cause for this cancer rise is still unclear.MRI,CT and PET provide useful diagnostic information in those patients.Surgical resection is the only chance for cure,with results depending on selected patients and careful surgical technique.Liver transplantation could offer long-term survival in selected patients when combined with chemotherapy.Chemotherapy,radiation therapy or combination therapies remain as the only treatment for inoperable patients.However,these are uniformly ineffective in patients' survival.

Preoperative portal vein embolization for hepatocellular carcinoma: consensus and controversy

Thirty years have passed since the first report of portal vein embolization(PVE),and this procedure is widely adopted as a preoperative treatment procedure for patients with a small future liver remnant(FLR).PVE has been shown to be useful in patients with hepatocellular carcinoma(HCC)and chronic liver disease.However,special caution is needed when PVE is applied prior to subsequent major hepatic resection in cases with cirrhotic livers,and volumetric analysis of the liver segments in addition to evaluation of the liver functional reserve before PVE is mandatory in such cases.Advances in the embolic material and selection of the treatment approach,and combined use of PVE and transcatheter arterial embolization/chemoembolization have yielded improved outcomes after PVE and major hepatic resections.A novel procedure termed the associating liver partition and portal vein ligation for staged hepatectomy has been gaining attention because of the rapid hypertrophy of the FLR observed in patients undergoing this procedure,however,application of this technique in HCC patients requires special caution,as it has been shown to be associated with a high morbidity and mortality even in cases with essentially healthy livers.

Surgical treatment of HCC in a patient with lamivudine-resistant hepatitis B cirrhosis with adefovir dipivoxil

We describe a 77-year-old woman with chronic hepatitis B who became resistant to lamivudine.She was started on adefovir(10 mg daily)while still continuing lamivudine therapy.Four mo later her liver function improved and serum Hepatitis B virus(HBV)-DNA level became undetectable.Three years after the start of additional adefovir treatment,hepatocellular carcinoma (HCC)was detected and the patient underwent a successful hepa-tectomy.Our findings suggest tha-t the addition of adefovir to ongoing lamivudine therapy cannot completely suppress hepatocarcinogenesis,but is useful for improving liver function in patients with lamivudine-resistant HBV-related cirrhosis,allowing HCC surgery.

Erythropoietin ameliorates early ischemia-reperfusion injury following the Pringle maneuver

AIM:To investigate the protective effect of erythropoietin (Epo) against ischemia-reperfusion injury (IR/I) following the Pringle maneuver (PM),in comparison with conventional steroid administration in a prospective randomized trial. METHODS:Patients were randomized by age, sex, diagnosis, and surgical method, and assigned to three groups:(1) A steroid group (STRD, n= 9) who received 100 mg of hydrocortisone before PM, and on postoperative days 1, 2 and 3, followed by tapering until postoperative day 7; (2) An EPO1 group (n=10) who received 30 000 U of Epo before the PM and at the end of surgery; and (3) An EPO2 group (n=8) who received 60 000 U of Epo before the PM. Hemoglobin (Hb), hematocrit (Ht), aspartate aminotransferase (AST), alanine transaminase (ALT),lactate dehydrogenase (LDH), lactate, interleukin-6 (IL-6),and tumor necrosis factor(TNF)-α were measured before and just after (Day 0) surgery, and on postoperative days 1, 3, 7 and 14. RESULTS: There were no increases in Hb and Ht in the EPO1 and EPO2 groups. AST was signif icantly lower in EPO1 than in STRD on Day 0 (P=0.041), and lower in EPO1 than in STRD and EPO2 on Day 1 (P=0.018). ALT was signif icantly lower in EPO1 than in STRD and EPO2 on Day 0 (P=0.020) and Day 1 (P=0.004). There were no signif icant inter-group differences in the levels of LDH and lactate. IL-6 was signif icantly lower in EPO1 than in STRD and EPO2 on Day 0 (P=0.0036) and Day 1 (P=0.0451). TNF-α was signif icantly lower in EPO1 than in STRD and EPO2 on Day 0 (P=0.0006) and Day 1 (P<0.0001). Furthermore, hospitalization was signif icantly shorter in EPO1 and EPO2 than in STRD.CONCLUSION:Epo has greater potential than steroids to ameliorate IR/I after the PM. Epo at a dose of 30000 U, administered before PM and just after surgery, yields better results.

Feasibility of single-incision laparoscopic cholecystectomy for acute cholecystitis

AIM: To assess the safety of single-incision laparoscopic cholecystectomy(SILC) for acute cholecystitis.METHODS: All patients who underwent SILC at Sano Hospital(Kobe, Japan) between January 2010 and December 2014 were included in this retrospective study. Clinical data related to patient characteristics and surgical outcomes were collected from medical records. The parameters for assessing the safety of the procedure included operative time, volume of blood loss, achievement of the critical view of safety, use of additional trocars, conversion to laparotomy, intraoperative and postoperative complications, and duration of postoperative hospital stay. Patient backgrounds were statistically compared between those with and without conversion to laparotomy.RESULTS: A total of 100 patients underwent SILC for acute cholecystitis during the period. Preoperative endoscopic treatment was performed for suspected choledocholithiasis in 41 patients(41%). The mean time from onset of acute cholecystitis was 7.7 d. According to the Updated Tokyo Guidelines(TG13) for the severity of cholecystitis, 86 and 14 patients had grade Ⅰ and grade Ⅱ acute cholecystitis, respectively. The mean operative time was 87.4 min. The mean estimated blood loss was 80.6 mL. The critical view of safety was obtained in 89 patients(89%). Conversion laparotomy was performed in 12 patients(12%). Postoperative complications of Clavien-Dindo grade Ⅲ or greater were observed in 4 patients(4%). The mean duration of postoperative hospital stay was 5.7 d. Patients converted from SILC to laparotomy tended to have higher days after onset.CONCLUSION: SILC is feasible for acute cholecystitis; in addition, early surgical intervention may reduce the risk of laparotomy conversion.

Edaravone inhibits apoptosis caused by ischemia/reperfusion injury in a porcine hepatectomy model

AIM： TO investigate the effect of E3-methyl-l-phe- nyl-2-pyrazolin-5-one （Edr） on hepatic ischemia-reper- fusion （I/R） injury and liver regeneration in a porcine hepatectomy model. METHODS： One hour ischemia was induced by occlud- ing the vessels and the bile duct of the right and median lobes. A 40% left hepatectomy was performed after re- perfusion. Six animals received Edr （3 mg/kg per hour） intravenously and six control animals received saline just before reperfusion. Remnant liver volume, hemody- namics, aspartate aminotransferase （AST）, alanine ami- notransferase, lactate dehydrogenase and lactic acid, were compared between the groups. The expression of transforming growth factor-β （TGF-β1） and toll-like receptor （TRL） mRNA in hepatic tissues was examined using reverse transcription polymerase chain reaction. Apoptosis was demonstrated by terminal deoxynucleo- tidyl transferase dUTP nick end labeling （TUNEL） stain- ing, respectively. RESULTS： Serum AS-I- （P = 0.029）, and toll like recep- tor 4 level （P = 0.043） were significantly lower after 3 hin animals receiving Edr. In addition, TUNEL staining in Edr-treated pigs showed significantly fewer hepatocytes undergoing apoptosis compared with control pigs. After 1 mo, all factors were non-significantly different between the two groups. CONCLUSION： Edr is considered to reduce hepatic injury in the early stage of I/R injury in a porcine model.

Primary hepatic leiomyosarcoma:Case report and literature review

Primary hepatic leiomyosarcoma are rare tumors with less than 30 cases reported in the English literature.Non specific presentations and often diagnosis delayed until they reach a large size,is the norm with therapy leading to an often dismal prognosis.A 67-year-old man presented complaining of abdominal pain and a palpable abdominal mass since Jan 2010.Abdominal ultrasonography and abdominal computed tomography revealed a large tumor in the left lobe of the liver.Surgical exploration was undertaken and an extended left hepatectomy with extension onto the dorsal part of segment 8 preserving the MHV with partial resection of segment 6 was undertaken.The weight of the resected specimen was 1300 g of the left lobectomy specimen and 8 g of the segment 6 partial resection specimen.The pathology report confirmed the diagnosis of leiomyosarcoma.On immunohistochemistry,the tumor cells were positive for smooth muscle actin stain.The patient is on regular follow up and is currently 9 mo post resection with no evidence of recurrence.We report the case of a resected primary hepatic leiomyosarcoma and emphasize the need for a global database for these rare tumors to promote a better and broader understanding of this less understood subject.

Short-and long-term outcomes of endoscopically treated superficial non-ampullary duodenal epithelial tumors

BACKGROUND It is widely recognized that endoscopic resection(ER) of superficial nonampullary duodenal epithelial tumors(SNADETs) is technically challenging and may carry high risks of intraoperative and delayed bleeding and perforation.These adverse events could be more critical than those occurring in other levels of the gastrointestinal tract. Because of the low prevalence of the disease and the high risks of severe adverse events, the curability including short-and long-term outcomes have not been standardized yet.AIM To investigate the curability including short-and long-term outcomes of ER for SNADETs in a large case series.METHODS This retrospective study included cases that underwent ER for SNADETs at our university hospital between March 2004 and July 2017. Short-term outcomes of ER were measured based on en bloc and R0 resection rates as well as adverse events. Long-term outcomes included local recurrence detected on endoscopic surveillance and disease-specific mortality in patients followed up for ≥ 12 mo after ER.RESULTS In the study, 131 patients with 147 SNADETs were analyzed. The 147 ERs consisted of 136 endoscopic mucosal resections(EMRs)(93%) and 11 endoscopic submucosal dissections(ESDs)(7%). The median tumor diameter was 10 mm.The pathology diagnosis was adenocarcinoma(56/147, 38%), high-grade intraepithelial neoplasia(44/147, 30%), or low-grade intraepithelial neoplasia(47/147, 32%). The R0 resection rate was 68%(93/136) in the EMR group and73%(8/11) in the ESD group, respectively. Cap-assisted EMR(known as EMR-C)showed a higher rate of R0 resection compared to the conventional method of EMR using a snare(78% vs 62%, P = 0.06). No adverse event was observed in the EMR group, whereas delayed bleeding, intraoperative perforation, and delayed perforation in 3, 3, and 5 patients occurred in the ESD group, respectively. One patient with perforation required emergency surgery. In the 43 mo median follow-up period, local recurrence was found in four EMR cases and all cases were treated endoscopically. No patient died due to tumor recurrence.CONCLUSION Our findings suggest that ER provides good long-term outcomes in the patients with SNADETs. EMR is likely to become the safe and reliable treatment for small SNADETs.

Molecular pathogenesis of sporadiccolorectal cancers

Colorectal cancer(CRC)results from the progressive accumulation of genetic and epigenetic alterations that lead to the transformation of normal colonic mucosa to adenocarcinoma.Approximately 75%of CRCs are sporadic and occur in people without genetic predisposition or family history of CRC.During the past two decades,sporadic CRCs were classified into three major groups according to frequently altered/mutated genes.These genes have been identified by linkage analyses of cancer-prone families and by individual mutation analyses of candidate genes selected on the basis of functional data.In the first half of this review,we describe the genetic pathways of sporadic CRCs and their clinicopathologic features.Recently,large-scale genome analyses have detected many infrequently mutated genes as well as a small number of frequently mutated genes.These infrequently mutated genes are likely described in a limited number of pathways.Gene-oriented models of CRC progression are being replaced by pathway-oriented models.In the second half of this review,we summarize the present knowledge of this research field and discuss its prospects.

Endoscopic ultrasonography can diagnose distal biliary strictures without a mass on computed tomography

AIM:To assess the diagnostic ability of endoscopic ultrasonography(EUS)for evaluating causes of dista biliary strictures shown on endoscopic retrograde chol angiopancreatography(ERCP)or magnetic resonance cholangiopancreatography(MRCP),even without iden tifiable mass on computed tomography(CT). METHODS:The diagnostic ability of EUS was retro spectively analyzed and compared with that of routine cytology(RC)and tumor markers in 34 patients with distal biliary strictures detected by ERCP or MRCP a Dokkyo Medical School Hospital from December 2005 to December 2008,without any adjacent mass or ec centric thickening of the bile duct on CT that could cause biliary strictures.Findings considered as benign strictures on EUS included preservation of the normasonographic layers of the bile duct wall,irrespective of the presence of a mass lesion.Other strictures were considered malignant.Final diagnosis of underlying diseases was made by pathological examination in 18 cases after surgical removal of the samples,and by clinical follow-up for>10 mo in 16 cases. RESULTS:Seventeen patients(50%)were finally di- agnosed with benign conditions,including 6"normal" subjects,while 17 patients(50%)were diagnosed with malignant disease.In terms of diagnostic ability,EUS showed 94.1%sensitivity,82.3%specificity,84.2% positive predictive value,93.3%negative predictive value(NPV)and 88.2%accuracy for identifying ma- lignant and benign strictures.EUS was more sensi- tive than RC(94.1%vs 62.5%,P=0.039).NPV was also better for EUS than for RC(93.3%vs 57.5%,P= 0.035).In addition,EUS provided significantly higher sensitivity than tumor markers using 100 U/mL as the cutoff level of carbohydrate antigen 19-9(94.1%vs 53%,P=0.017).On EUS,biliary stricture that was fi- nally diagnosed as malignant showed as a hypoechoic, irregular mass,with obstruction of the biliary duct and invasion to surrounding tissues. CONCLUSION:EUS can diagnose biliary strictures caused by malignant tumors that are undetectable on CT.Earlier detection by EUS would provide more therapeutic options for patients with early-stage pancreaticobiliary cancer.

Gastroduodenal ulcer bleeding in elderly patients on low dose aspirin therapy

AIM To determine the clinical characteristics of elderly patients of hemorrhagic gastroduodenal ulcer on low-dose aspirin(LDA)therapy.METHODS A total of 1105 patients with hemorrhagic gastroduodenal ulcer treated in our hospital between January 2000 and March 2016 were grouped by age and drugs used,and these groups were compared in several factors.These groups were compared in terms of length of hospital stay,presence/absence of hemoglobin(Hb)decrease,presence/absence of blood transfusion,Forrest Ⅰ,percentage of Helicobacter pylori infection,presence/absence of underlying disease,and percentage of severe cases.RESULTS The percentage of blood transfusion(62.6%vs 47.7%,P<0.001),Hb decrease(53.8% vs 40.8%,P<0.001),and the length of hospital stay(23.5 d vs 16.7 d,P<0.001)were significantly greater in those on drug therapy.The percentage of blood transfusion(65.3%vs 47.8%,P<0.001),Hb decrease(54.2%vs 42.1%,P<0.001),and length of hospital stay(23.3 d vs 17.5 d,P<0.001)were significantly greater in the elderly.In comparison with the LDA monotherapy group,the percentage of severe cases was significantly higher in the LDA combination therapy group when elderly patients were concerned(16.1%vs34.0%,P=0.030).Meanwhile,among those on LDA monotherapy,there was no significant difference between elderly and non-elderly(16.1%vs 16.0%,P=0.985).CONCLUSION A combination of LDA with antithrombotic drugs or nonsteroidal anti-inflammatory drugs(NSAIDs)contributes to aggravation.And advanced age is not an aggravating factor when LDA monotherapy is used.

Intraoperative frozen section diagnosis of bile duct margin for extrahepatic cholangiocarcinoma

AIM To evaluate the usefulness of frozen section diagnosis(FSD) of bile duct margins during surgery for extrahepatic cholangiocarcinoma(CCA). METHODS We retrospectively analyzed 74 consecutive patients who underwent surgery for extrahepatic CCA from 2012 to 2017, during which FSD of bile duct margins was performed. They consisted of 40 distant and 34 perihilar CCAs(45 and 55 bile duct margins, respectively). The diagnosis was classified into three categories: negative, borderline(biliary intraepithelial neoplasia-1 and 2, and indefinite for neoplasia), or positive. FSD in the epithelial layer, subepithelial layer, and total layer was compared with corresponding permanent section diagnosis(PSD) postoperatively.Then, association between FSD and local recurrence was analyzed with special reference to borderline.RESULTS Analysis of 100 duct margins revealed that concordance rate between FSD and PSD was 68.0% in the total layer, 69.0% in the epithelial layer, and 98.0% in the subepithelial layer. The extent of remaining biliary epithelium was comparable between FSD and PSD, and more than half of the margins lost > 50% of the entire epithelium, suggesting low quality of the samples. In FSD, the rate of negative margins decreased and that of borderline and positive margins increased according to the extent of the remaining epithelium. Diagnostic discordance between FSD and PSD was observed in 31 epithelial layers and two subepithelial layers. Alteration from borderline to negative was the most frequent(20 of the 31 epithelial layers). Patients with positive margin in the total and epithelial layers by FSD demonstrated a significantly worse local recurrence-free survival(RFS) compared with patients with borderline and negative margins, which revealed comparable local RFS. Patients with borderline and negative margins in the epithelial layer by PSD also revealed comparable local RFS. These results suggested that epithelial borderline might be regarded substantially as negative. When classifying the status of the epithelial layer either as negative or positive, concordance rates between FSD and PSD in the total, epithelial, and subepithelial layers were 95.0%, 93.0%, and 98.0%, respectively.CONCLUSION During intraoperative assessment of bile duct margin, borderline in the epithelial layer can be substantially regarded as negative, under which condition FSD is comparable to PSD.

Shear wave elastography in hepatitis C patients before and after antiviral therapy

AIMTo investigate shear wave (SW) propagation velocity in patients with untreated hepatitis C and patients with sustained virological response (SVR). METHODSA total of 136 hepatitis C patients [85 patients who had not received antiviral therapy (na&iuml;ve group) and 51 patients who had received antiviral therapy and subsequently achieved SVR of at least 24 wk (SVR group)] and 58 healthy volunteers and outpatients without liver disease (control group) underwent evaluation of liver stiffness by SW elastography (SWE). Various parameters were evaluated in the chronic hepatitis C patients at the time of SWE. RESULTSSW propagation velocity (Vs) was 1.23 &plusmn; 0.14 m/s in the control group, 1.56 &plusmn; 0.32 m/s in the SVR group, and 1.69 &plusmn; 0.31 m/s in the na&iuml;ve group. Significant differences were seen between the control group and the SVR group (P = 0.0000) and between the SVR group and the na&iuml;ve group (P = 0.01417). All four fibrosis markers were higher in the na&iuml;ve group than in the SVR group. In the na&iuml;ve group, Vs was positively correlated with alanine aminotransferase (ALT) (r = 0.5372), &alpha; feto protein (AFP) (r = 0.4389), type IV collagen (r = 0.5883), procollagen III peptide (P-III-P) (r = 0.4140), hyaluronic acid (r = 0.4551), and Mac-2 binding protein glycosylation isomer (M2BPGi) (r = 0.6092) and negatively correlated with albumin (r = -0.4289), platelets (r = -0.5372), and prothrombin activity (r = -0.5235). On multiple regression analysis, Vs was the most strongly correlated with ALT (standard partial regression std &beta; = 0.4039, P = 0.00000). In the SVR group, Vs was positively correlated with AFP (r = 0.6977), type IV collagen (r = 0.5228), P-III-P (r = 0.5812), hyaluronic acid (r = 0.5189), and M2BPGi (r = 0.6251) and negatively correlated with albumin (r = -0.4283), platelets (r = -0.4842), and prothrombin activity (r = -0.4771). On multiple regression analysis, Vs was strongly correlated with AFP (standard partial regression std &beta; = 0.5953, P = 0.00000) and M2BPGi (standard partial regression std &beta;= 0.2969, P = 0.03363). CONCLUSIONIn hepatitis C patients, liver stiffness is higher in treatment-na&iuml;ve patients than in those showing SVR. SWE may be a predictor of hepatocarcinogenesis in SVR patients.

MK615 decreases RAGE expression and inhibits TAGE-induced proliferation in hepatocellular carcinoma cells

AIM:To investigate the proliferative effect of advanced glycation end-products(AGEs) and the role of their cellular receptor(RAGE) on hepatocellular carcinoma(HCC) cells,and the inhibitory effects of MK615,an extract from Japanese apricot,against AGEs were also evaluated.METHODS:Two HCC cell lines,HuH7 and HepG2,were used.Expression of RAGE was investigated by poly-merase chain reaction,Western blotting,and flow cytemetry(FACS).The effect of MK615 on RAGE expression was also evaluated by FACS.The proliferative effects of a control(unglycated bovine serum albumin),glucosederived AGEs(Glc-AGE),and glyceraldehyde-derived AGEs(Glycer-AGE),and the anti-proliferative effect of MK615 against AGEs,were evaluated using MTT assays.RESULTS:Expression of RAGE was confirmed at both the mRNA and protein levels in both HuH7 and HepG2.FACS revealed that the level of RAGE expression was higher in HuH7 than in HepG2.Treatment with 0.1 μg/mL MK615 decreased the expression level of RAGE from 24.3% to 3.7% in HuH7 and from 6.2% to 4.8% in HepG2.The growth indices for the control,Glc-AGE,and Glycer-AGE were 1.06 ± 0.08,0.99 ± 0.04,and 1.38 ± 0.05,respectively,in HuH7(P = 0.037),and were 1.03 ± 0.04,1.04 ± 0.03,and 1.07 ± 0.05,respectively,in HepG2(P > 0.05).When the cells were cultured simultaneously with Glycer-AGE and MK615,MK615 abrogated the proliferative effect of Glycer-AGE in HuH7.CONCLUSION:Only Glycer-AGE has a proliferative effect on HuH7,which expresses a higher level of RAGE.MK615 suppresses the proliferative effect of GlycerAGE on HuH7 by decreasing the expression of RAGE.

Role of bile acid sequestrants in the treatment of type 2 diabetes

Cholestyramine is a first-generation bile acid sequestrant(BAS) and antihyperlipidemic agent that currentl y has limited use because of its relatively weak effect on lowering low density-lipoprotein(LDL)-chol es terol(C) and poor tolerability.The current first choice drugs for hyper-LDL-cholesterolemia are 3-hy droxy-3-me t hyl-glutaryl coenzyme A reductase inhibitors(statins) because of their strong LDL-C lowering effects and efficacy in prevention of card io vascular disease.Howe ver,after lowering the target levels of LDL-C in very high risk patients,combination therapy with statins and other antihyper lipidemic drugs may become more important for treatment of hyper-LDL-cholesterolemia.Second-generation BASs such as coles evelam and colestimide have a glucose-lowering effect and improved tolerance,which has led to re-evaluation of their utility in combination with statins or antidiabetic agents.

Pulmonary artery sarcoma successfully treated by right pneumonectomy after definitive diagnosis

Pulmonary artery sarcoma(PAS)is a rare and lethal neoplasm that is usually diagnosed during surgery or autopsy.Early diagnosis and radical surgical resection offer the only chance for survival.However,making a preoperative histopathological diagnosis is quite difficult.We encountered a 57-year-old woman presenting a PAS that mimicked a pulmonary thromboembolism.After confirming a definitive diagnosis using a catheter suction biopsy,we successfully performed a right pneumonectomy via a median sternotomy without cardiopulmonary bypass.Eighteen months after surgery,no recurrence was observed.