Effects of mesenchymal stem cell on dopaminergic neurons,motor and memory functions in animal models of Parkinson's disease:a systematic review and meta-analysis

Parkinson’s disease is chara cterized by the loss of dopaminergic neurons in the substantia nigra pars com pacta,and although restoring striatal dopamine levels may improve symptoms,no treatment can cure or reve rse the disease itself.Stem cell therapy has a regenerative effect and is being actively studied as a candidate for the treatment of Parkinson’s disease.Mesenchymal stem cells are considered a promising option due to fewer ethical concerns,a lower risk of immune rejection,and a lower risk of teratogenicity.We performed a meta-analysis to evaluate the therapeutic effects of mesenchymal stem cells and their derivatives on motor function,memory,and preservation of dopamine rgic neurons in a Parkinson’s disease animal model.We searched bibliographic databases(PubMed/MEDLINE,Embase,CENTRAL,Scopus,and Web of Science)to identify articles and included only pee r-reviewed in vivo interve ntional animal studies published in any language through J une 28,2023.The study utilized the random-effect model to estimate the 95%confidence intervals(CI)of the standard mean differences(SMD)between the treatment and control groups.We use the systematic review center for laboratory animal expe rimentation’s risk of bias tool and the collaborative approach to meta-analysis and review of animal studies checklist for study quality assessment.A total of 33studies with data from 840 Parkinson’s disease model animals were included in the meta-analysis.Treatment with mesenchymal stem cells significantly improved motor function as assessed by the amphetamine-induced rotational test.Among the stem cell types,the bone marrow MSCs with neurotrophic factor group showed la rgest effect size(SMD[95%CI]=-6.21[-9.50 to-2.93],P=0.0001,I^(2)=0.0%).The stem cell treatment group had significantly more tyrosine hydroxylase positive dopamine rgic neurons in the striatum([95%CI]=1.04[0.59 to 1.49],P=0.0001,I^(2)=65.1%)and substantia nigra(SMD[95%CI]=1.38[0.89 to 1.87],P=0.0001,I^(2)=75.3%),indicating a protective effect on dopaminergic neurons.Subgroup analysis of the amphetamine-induced rotation test showed a significant reduction only in the intracranial-striatum route(SMD[95%CI]=-2.59[-3.25 to-1.94],P=0.0001,I^(2)=74.4%).The memory test showed significant improvement only in the intravenous route(SMD[95%CI]=4.80[1.84 to 7.76],P=0.027,I^(2)=79.6%).Mesenchymal stem cells have been shown to positively impact motor function and memory function and protect dopaminergic neurons in preclinical models of Parkinson’s disease.Further research is required to determine the optimal stem cell types,modifications,transplanted cell numbe rs,and delivery methods for these protocols.

Short- and long-term outcomes of surgical treatment in patients with intestinal Behcet’s disease

BACKGROUND Behcet’s disease(BD),a chronic vasculitic disorder affecting multiple organs,is characterized by recurrent oral and genital ulcers,arthritis,vasculitis,and intes-tinal ulcers.Although intestinal involvement of BD is common in East Asia,the efficacy and long-term outcomes of surgical treatment of intestinal BD still remain to be established.AIM To evaluate the postoperative clinical course of intestinal BD and determine factors associated with its recurrence.METHODS Data from patients who underwent surgical treatment for intestinal BD between January 2010 and August 2021 were retrospectively reviewed.Patients’demo-graphics,clinical features,postoperative course,complications,and follow-up data were evaluated.RESULTS We analyzed 39 surgeries in 31 patients.The mean patient age was 45.1 years,and the mean interval between the diagnosis of intestinal BD and surgical treatment was 4.9 years(range 1.0-8.0 years).The most common indication for surgery was medical intractability(n=16,41.0%),followed by fistula or abscess(n=11,28.2%).Laparoscopic approaches were used in 19 patients(48.7%),and 5 patients(12.8%)underwent emergency surgeries.The most common surgical procedure was ileocecal resection(n=18,46.2%),followed by right colectomy(n=11,28.2%).A diverting stoma was created in only one patient(2.6%).During a mean follow-up period of 45(range 8-72)months,eight cases(20.5%)of recurrence in five patients required reoperation.The interval between operations was 12.1 months(range 6.3-17.8 mo).Four patients(10.3%)experienced recurrence within 1 year postoperatively,and all eight recurrences occurred within 2 years of the initial surgery.The reoperation rates at 1 and 3 years were 10.3%and 20.5%,respectively.A redo ileocolic anastomosis was performed in all recurrent cases.In multivariate Cox regression analysis,emergency surgery[hazard ratio(HR)9.357,95%confidence interval(CI):1.608-54.453,P=0.013]and elevated C-reactive protein(CRP)levels(HR 1.154,95%CI:1.002–1.328,P=0.047),but not medication use,were predictors of recurrence.CONCLUSION Surgical resection is a feasible treatment option for complicated BD.Reoperation is associated with severe inflam-matory conditions,reflected by increased CRP levels and the requirement for emergency surgery.

Neural Wiskott-Aldrich syndrome protein(N-WASP)promotes distant metastasis in pancreatic ductal adenocarcinoma via activation of LOXL2

Pancreatic ductal adenocarcinoma(PDAC)is one of the most aggressive solid malignancies.A specific mechanism of its metastasis has not been established.In this study,we investigated whether Neural Wiskott-Aldrich syndrome protein(N-WASP)plays a role in distant metastasis of PDAC.We found that N-WASP is markedly expressed in clinical patients with PDAC.Clinical analysis showed a notably more distant metastatic pattern in the N-WASP-high group compared to the N-WASP-low group.N-WASP was noted to be a novel mediator of epithelialmesenchymal transition(EMT)via gene expression profile studies.Knockdown of N-WASP in pancreatic cancer cells significantly inhibited cell invasion,migration,and EMT.We also observed positive association of lysyl oxidase-like 2(LOXL2)and focal adhesion kinase(FAK)with the N-WASP-mediated response,wherein EMT and invadopodia function were modulated.Both N-WASP and LOXL2 depletion significantly reduced the incidence of liver and lung metastatic lesions in orthotopic mouse models of pancreatic cancer.These results elucidate a novel role for N-WASP signaling associated with LOXL2 in EMT and invadopodia function,with respect to regulation of intercellular communication in tumor cells for promoting pancreatic cancer metastasis.These findings may aid in the development of therapeutic strategies against pancreatic cancer.

Monogenic features of urolithiasis: A comprehensive review

Objective: Urolithiasis formation has been attributed to environmental and dietary factors. However, evidence is accumulating that genetic background can contribute to urolithiasis formation. Advancements in the identification of monogenic causes using high-throughput sequencing technologies have shown that urolithiasis has a strong heritable component.Methods: This review describes monogenic factors implicated in a genetic predisposition to urolithiasis. Peer-reviewed journals were evaluated by a PubMed search until July 2023 to summarize disorders associated with monogenic traits, and discuss clinical implications of identification of patients genetically susceptible to urolithiasis formation.Results: Given that more than 80% of urolithiases cases are associated with calcium accumulation, studies have focused mainly on monogenetic contributors to hypercalciuric urolithiases, leading to the identification of receptors, channels, and transporters involved in the regulation of calcium renal tubular reabsorption. Nevertheless, available candidate genes and linkage methods have a low resolution for evaluation of the effects of genetic components versus those of environmental, dietary, and hormonal factors, and genotypes remain undetermined in the majority of urolithiasis formers.Conclusion: The pathophysiology underlying urolithiasis formation is complex and multifactorial, but evidence strongly suggests the existence of numerous monogenic causes of urolithiasis in humans.

Long-term outcome of stem cell transplantation with and without anti-tumor necrotic factor therapy in perianal fistula with Crohn’s disease

BACKGROUND Stem cell transplantation is a promising therapeutic option for curing perianal fistula in Crohn’s disease(CD).Anti-tumor necrotic factor(TNF)therapy combined with drainage procedure is effective as well.However,previous studies are limited to proving whether the combination treatment of biologics and stem cell transplantation improves the effect of fistula closure.AIM This study aimed to evaluate the long-term outcomes of stem cell transplantation and compare Crohn’s perianal fistula(CPF)closure rates after stem cell transplantation with and without anti-TNF therapy,and to identify the factors affecting CPF closure and recurrence.METHODS The patients with CD who underwent stem cell transplantation for treating perianal fistula in our institution between Jun 2014 and December 2022 were enrolled.Clinical data were compared according to anti-TNF therapy and CPF closure.RESULTS A total of 65 patients were included.The median age of females was 26 years(range:21-31)and that of males was 29(44.6%).The mean follow-up duration was 65.88±32.65 months,and complete closure was observed in 50(76.9%)patients.The closure rates were similar after stem cell transplantation with and without anti-TNF therapy(66.7%vs 81.6%at 3 year,P=0.098).The patients with fistula closure had short fistulous tract and infrequent proctitis and anorectal stricture(P=0.027,0.002,and 0.008,respectively).Clinical factors such as complexity,number of fistulas,presence of concurrent abscess,and medication were not significant for closure.The cumulative 1-,2-,and 3-year closure rates were 66.2%,73.8%,and 75.4%,respectively.CONCLUSION Anti-TNF therapy does not increase CPF closure rates in patients with stem cell transplantation.However,both refractory and non-refractory CPF have similar closure rates after additional anti-TNF therapy.Fistulous tract length,proctitis,and anal stricture are risk factors for non-closure in patients with CPF after stem cell transplantation.

A pilot clinical study to evaluate feasibility of using single patient classifier as a prognostic test in stage Ⅱ-Ⅲ gastric cancer patients

Objective:Precision medicine approaches emphasize the importance of reliable prognostic tools for guiding individualized therapy decisions.In this study,we evaluated the clinical feasibility of the single patient classifier(SPC)test,a new clinical-grade prognostic assay,in stageⅡ-Ⅲgastric cancer patients.Methods:A prospective multicenter study was conducted,involving 237 patients who underwent gastrectomy between September 2019 and August 2020 across nine hospitals.The SPC test was employed to stratify patients into risk groups,and its feasibility and performance were evaluated.The primary endpoint was the proportion of the cases in which the test results were timely delivered before selecting postoperative treatment.Furthermore,3-year disease-free survivals of risk groups were analyzed.Results:The SPC test met the primary endpoint criteria.The 99.5%of SPC tests were timely delivered to hospitals before the postoperative treatment started.In a clinical setting,the median time from the specimen transfer to laboratory to the result delivery to hospital was 4 d.Furthermore,3-year disease-free survivals were significantly different between risk groups classified with SPC tests.Conclusions:This study highlights the SPC test's feasibility in offering crucial information timely delivered for making informed decisions regarding postoperative treatment strategies.It also provides evidence to support the implementation of a future prospective clinical trial aimed at evaluating the clinical utility of the SPC test in guiding personalized treatment decisions for gastric cancer patients.

Efficacy and safety of rebamipide/nizatidine in patients with erosive gastritis: A randomized, multicenter, phase 4 study

BACKGROUND For the treatment of gastritis,rebamipide,a mucoprotective agent,and nizatidine,a gastric acid suppressant,are commonly employed individually.AIM To compare the efficacy of Mucotra®SR(rebamipide 150 mg)and Axid®(nizatidine 150 mg)combination therapy with the sole administration of Axid®in managing erosive gastritis.METHODS A total of 260 patients diagnosed with endoscopically confirmed erosive gastritis were enrolled in this open-label,multicenter,randomized,phase 4 clinical trial,allocating them into two groups:Rebamipide/nizatidine combination twice daily vs nizatidine twice daily for 2 weeks.The full-analysis set analysis encompassed 239 patients(rebamipide/nizatidine,n=121;nizatidine,n=118),while the per-protocol analysis included 218 patients(n=110 vs 108).Post-treatment assessments comprised primary(erosion improvement rate)and secondary(erosion and edema cure rates,erythema improvement rates,hemorrhage,and gastrointestinal symptoms)endpoints.Furthermore,drug-related adverse effects were evaluated.RESULTS Primary efficacy assessment showed a statistically significant improvement rate in mucosal erosions in the combination group compared to the control group in the full-analysis set(rebamipide/nizatidine 62.0%,nizatidine 49.2%,P=0.046),with a similar trend noted in the per-protocol analysis(62.7%vs 50.0%,P=0.058).Both groups were effective in curing erosion and edema and improvement of bleeding,erythema,and gastrointestinal symptoms,whereas no inter-group differences were noted.When confined to the participants with gastritis symptoms,improvement of erosion was more optimal in the combination group(63.0%vs 49.5%,P=0.046).No adverse events related to the drugs were observed.CONCLUSION Rebamipide/nizatidine combination is effective in treatment of erosive gastritis.

Non-invasive diagnosis of hepatitis B virus-related cirrhosis

Chronic hepatitis B(CHB)infection is a major public health problem associated with significant morbidity and mortality worldwide.Twenty-three percent of patients with CHB progress naturally to liver cirrhosis,which was earlier thought to be irreversible.However,it is now known that cirrhosis can in fact be reversed by treatment with oral anti-nucleotide drugs.Thus,early and accurate diagnosis of cirrhosis is important to allow an appropriate treatment strategy to be chosen and to predict the prognosis of patients with CHB.Liver biopsy is the reference standard for assessment of liver fibrosis.However,the method is invasive,and is associated with pain and complications that can be fatal.In addition,intra-and inter-observer variability compromises the accuracy of liver biopsy data.Only small tissue samples are obtained and fibrosis is heterogeneous in such samples.This confounds the two types of observer variability mentioned above.Such limitations have encouraged development of non-invasive methods for assessment of fibrosis.These include measurements of serum biomarkers of fibrosis;and assessment of liver stiffness via transient elastography,acoustic radiation force impulse imaging,real-time elastography,or magnetic resonance elastography.Although significant advances have been made,most work to date has addressed the diagnostic utility of these techniques in the context of cirrhosis caused by chronic hepatitis C infection.In the present review,we examine the advantages afforded by use of non-invasive methods to diagnose cirrhosis in patients with CHB infections and the utility of such methods in clinical practice.

Characterization of focal liver masses using acoustic radiation force impulse elastography

AIM:To investigate the diagnostic performance of acoustic radiation force impulse(ARFI) elastography for characterizing focal liver mass by quantifying their stiffness.METHODS:This prospective study included 62 patients with a focal liver mass that was well visualized on conventional ultrasonography performed in our institution from February 2011 to November 2011.Among them,12 patients were excluded for ARFI measurement failure due to a lesion that was smaller than the region of the interest and at an inaccessible location(deeper than 8 cm)(n = 7) or poor compliance to hold their breath as required(n = 5).Finally,50 patients with valid ARFI measurements were enrolled.If a patient had multiple liver masses,only one mass of interest was chosen.The masses were diagnosed by histological examination or clinical diagnostic criteria.During ultrasonographic evaluation,stiffness,expressed as velocity,was checked 10 times per focal liver mass and the surrounding liver parenchyma.RESULTS:After further excluding three masses that were non-diagnostic on biopsy,a total of 47 focal mass lesions were tested,including 39(83.0%) malignant masses [24 hepatocellular carcinomas(HCC),seven cholangiocellular carcinomas(CCC),and eight liver metastases] and eight(17.0%) benign masses(five hemangiomas and three focal nodular hyperplasias,FNH).Thirty-seven(74.0%) masses were confirmed by histological examination.The mean velocity was 2.48 m/s in HCCs,1.65 m/s in CCCs,2.35 m/s in metastases,1.83 m/s in hemangiomas,and 0.97 m/s in FNHs.Although considerable overlap was still noted between malignant and benign masses,significant differences in ARFI values were observed between malignant and benign masses(mean 2.31 m/s vs 1.51 m/s,P = 0.047),as well as between HCCs and benign masses(mean 2.48 m/s vs 1.51 m/s,P = 0.006).The areas under the receiver operating characteristics curves(AUROC) for discriminating the malignant masses from benign masses was 0.724(95%CI,0.566-0.883,P = 0.048),and the AUROC for discriminating HCCs from benign masses was 0.813(95%CI,0.649-0.976,P = 0.008).To maximize the sum of sensitivity and specificity,an ARFI value of 1.82 m/s was selected as the cutoff value to differentiate malignant from benign liver masses.Furthermore,the cutoff value for distinguishing HCCs from benign masses was also determined to be 1.82 m/s.The diagnostic performance of the sum of the ARFI values for focal liver masses and the surrounding liver parenchyma to differentiate liver masses improved(AUROC = 0.853;95%CI,0.745-0.960;P = 0.002 in malignant liver masses vs benign ones and AUROC = 0.948;95%CI,0.896-0.992,P < 0.001 in HCCs vs benign masses).CONCLUSION:ARFI elastography provides additional information for the differential diagnosis of liver masses.However,our results should be interpreted in clinical context,because considerable overlap in ARFI values existed among liver masses.

Analysis of demographic characteristics in 3242 young age gastric cancer patients in Korea

AIM:To evaluate the epidemiologic features of young age gastric cancer(GC). METHODS:Retrospectively,a total of 3242 patients with GC between 18 and 45 years of age and 3000 sex-and age-matched controls were reviewed.All subjects were stratified into 3 groups based on age (A,18-30 years;B,31-40 years;C,41-45 years). Epidemiologic characteristics and risk factors were investigated with reference to their age and gender. RESULTS:Compared to controls,more frequent intake of high risk diet(P=0.00075),history of heavy smoking(P=0.00087),intake of heavy alcohol(P= 0.00091),lower social economic status(P=0.00083), body mass index>30(P=0.00097),urban residence(P=0.00065),and more frequent exposure to harmful occupational environments(P=0.00072)were observed in all age groups and both genders in young age GC.These relationships were weaker in females compared to males of the same age,and were stronger as the age of patients increased.However,in group C of young age GC patients,environmental factors played important roles in females and males with a similar body weight.In females,older age at first delivery(> 35 years),lack of lactation history,nulliparity,and poor nutritional status during pregnancy were significantly associated with an increased risk of GC(P=0.00034). In this study,252 patients(7.8%)had a family history of GC with high odds ratio(OR)(3.22-4.21).In particular, family history was more closely associated with GC in males(OR,4.21 in male vs 3.46 in female)and more advanced cases(P=0.00051). CONCLUSION:Hormonal associated factors were more commonly associated with females whereas environmental factors were more commonly associated with males in young age GC patients.

Role of the tumor microenvironment in the pathogenesis of gastric carcinoma

Gastric carcinoma (GC) is the 4th most prevalent cancer and has the 2nd highest cancer-related mortality rate worldwide. Despite the incidence of GC has decreased over the past few decades, it is still a serious health problem. Chronic inflammatory status of the stomach, caused by the infection of Helicobacter pylori (H. pylori) and through the production of inflammatory mediators within the parenchyma is suspected to play an important role in the initiation and progression of GC. In this review, the correlation between chronic inflammation and H. pylori infection as an important factor for the development of GC will be discussed. Major components, including tumor-associated macrophages, lymphocytes, cancer-associated fibroblasts, angiogenic factors, cytokines, and chemokines of GC microenvironment and their mechanism of action on signaling pathways will also be discussed. Increasing our understanding of how the components of the tumor microenviroment interact with GC cells and the signaling pathways involved could help identify new therapeutic and chemopreventive targets.

Prediction models of hepatocellular carcinoma development in chronic hepatitis B patients

Chronic hepatitis B virus(HBV) infection is a major cause of cirrhosis and hepatocellular carcinoma(HCC). Applying the same strategies for antiviral therapy and HCC surveillance to all chronic hepatitis B(CHB) patients would be a burden worldwide. To properly manage CHB patients, it is necessary to identify and classify the risk for HCC development in such patients. Several HCC risk scores based on risk factors such as cirrhosis, age, male gender, and high viral load have been used, and have negative predictive values of ≥ 95%. Most of these have been derived from, and internally validated in, treatment-na?ve Asian CHB patients. Herein, we summarized various HCC prediction models, including IPM(Individual Prediction Model), CU-HCC(Chinese University-HCC), GAG-HCC(Guide with Age, Gender, HBV DNA, Core Promoter Mutations and Cirrhosis-HCC), NGM-HCC(NomogramHCC), REACH-B(Risk Estimation for Hepatocellular Carcinoma in Chronic Hepatitis B), and Page-B score. To develop a noninvasive test of liver fibrosis, we also introduced a new scoring system that uses liver stiffness values from transient elastography, including an LSM(Liver Stiffness Measurement)-based model, LSM-HCC, and mR EACH-B(modified REACH-B).

Comparison of the efficacy and safety of sedation between dexmedetomidine-remifentanil and propofol-remifentanil during endoscopic submucosal dissection

AIM: To compare the efficacy and safety of sedation protocols for endoscopic submucosal dissection(ESD) between dexmedetomidine-remifentanil and propofolremifentanil.METHODS: Fifty-nine patients scheduled for ESD were randomly allocated into a dexmedetomidineremifentanil(DR) group or a propofol-remifentanil(PR) group. To control patient anxiety, dexmedetomidine or propofol was infused to maintain a score of 4-5 on the Modified Observer's Assessment of Alertness/Sedation scale. Remifentanil was infused continuously at a rate of 6 μg/kg per hour in both groups. The ease of advancing the scope into the throat, gastric motility grading, and satisfaction of the endoscopist and patient were assessed. Hemodynamic variables and hypoxemic events were compared to evaluate patient safety.RESULTS: Demographic data were comparable between the groups. The hemodynamic variables and pulse oximetry values were stable during the procedure in both groups despite a lower heart rate in the DR group. No oxygen desaturation events occurred in either group. Although advancing the scope into the throat was easier in the PR group("very easy" 24.1% vs 56.7%, P = 0.010), gastric motility was moresuppressed in the DR group("no + mild" 96.6% vs 73.3%, P = 0.013). The endoscopists felt that the procedure was more favorable in the DR group("very good + good" 100% vs 86.7%, P = 0.042), whereas patient satisfaction scores were comparable between the groups. En bloc resection was performed 100% of the time in both groups, and the complete resection rate was 94.4% in the DR group and 100% in the PR group(P = 0.477). CONCLUSION: The efficacy and safety of dexmedetomidine and remifentanil were comparable to propofol and remifentanil during ESD. However, the endoscopists favored dexmedetomidine perhaps due to lower gastric motility.

Clinical characteristics and treatment of inflammatory bowel disease: A comparison of Eastern and Western perspectives

Inflammatory bowel disease(IBD) is a chronic, relapsing intestinal inflammatory disorder with unidentified causes. Both environmental factors and genetic aspects are believed to be crucial to the pathogenesis of IBD. The incidence and prevalence of IBD have recently been increasing throughout Asia, presumably secondary to environmental changes. This increasing trend in IBD epidemiology necessitates specific health care planning and education in Asia. To this end, we must gain a precise understanding of the distinctive clinical and therapeutic characteristics of Asian patients with IBD. The phenotypes of IBD reportedly differ considerably between Asians and Caucasians. Thus, use of the same management strategies for these different populations may not be appropriate. Moreover, investigation of the Asian-specific clinical aspects of IBD offers the possibility of identifying causative factors in the pathogenesis of IBD in this geographical area. Accordingly, this review summarizes current knowledge of the phenotypic manifestations and management practices of patients with IBD, with a special focus on a comparisonof Eastern and Western perspectives.

Benefit of neoadjuvant concurrent chemoradiotherapy for locally advanced perihilar cholangiocarcinoma

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.

Comparison of hydrocolonic sonograpy accuracy in preoperative staging between colon and rectal cancer

AIM:To compare the accuracy of hydrocolonic sonography (HUS) in determining the depth of invasion (T stage) in colon and rectal cancer. METHODS:A total of 1000-2000 mL of saline was instilled per rectum using a system for barium enemas,and then ultrasonography was conducted by a SSA-270A (Toshiba Co,Japan) sonolayer unit with a 3.75 MHz for 17 patients with colon cancer and 13 patients with rectal cancer before operation.After operation,T stage in HUS was compared with postoperative histological findings. RESULTS:Overall,the accuracy of T stage was 70%.It was 88% in colon cancer and 46% in rectal cancer.In evaluating nodal state,the accuracy of HUS was low in both colon (71%) and rectal cancers (46%) compared with conventional CT or MRI.The overall accuracy of N staging was 60%. CONCLUSION:HUS is valuable to evaluate the depth of invasion in colon cancer,but is less valuable in rectal cancer.Because HUS is low-cost,noninvasive,and readily available at any place,this technique seems to be useful to determine the preoperative staging in colon cancer,but not in rectal cancer.

Clinical application of liver stiffness measurement using transient elastography in chronic liver disease from longitudinal perspectives

Accurate determination of the presence and degree of fibrosis in liver is of great importance, because the prognosis and management strategies for chronic liver disease depend mainly on these factors. To date, liver biopsy (LB) remains the "gold standard" for assessing the severity of liver fibrosis; however, LB is often limited by its invasiveness, sampling error, and intra/ inter-observer variability in histological interpretation. Furthermore, repeated LB examinations within a short time interval are indeed ineligible in a real clinical practice. Thus, due to the pressing need for non-invasive surrogates for liver fibrosis, transient elastography (TE),as a novel ultrasound based technology, has allowed a noninvasive measurement of liver stiffness and has gained in popularity over recent years. In the past few years, additional roles for transient TE beyond the initial purpose of a non-invasive surrogate for LB have included the prediction of the most two critical consequences of fibrosis progression: the development of portal hypertension-related complications and hepatocellular carcinoma. This indicates that the role of transient TE is not merely limited to reducing the need for LB, but transient TE can enable the establishment of tailored management strategies by providing more detailed prognostic information. In particular, under the concept in which the clinical course of liver fibrosis is dynamic and bidirectional, especially when appropriate intervention is commenced, transient TE can be used to track the dynamic changes in fibrotic burden during antiviral or antifibrotic treatment. This review discussed extended applications of transient TE in prediction of the development of real clinical endpoints from a longitudinal perspective.

Role of surgical resection for multiple hepatocellular carcinomas

AIM:To clarify the role of surgical resection for multiple hepatocellular carcinomas(HCCs)compared to transarterial chemoembolization(TACE)and liver transplantation(LT). METHODS:Among the HCC patients who were managed at Yonsei University Health System between January 2003 and December 2008,160 patients who met the following criteria were retrospectively enrolled:(1) two or three radiologically diagnosed HCCs;(2)no radiologic vascular invasion;(3)Child-Pugh class A;(4) main tumor smaller than 5 cm in diameter;and(5) platelet count greater than 50 000/mm3.Long-term outcomes were compared among the following three treatment modalities:surgical resection or combined radiofrequency ablation(RFA)(n=36),TACE(n=107), and LT(n=17).The survival curves were computed using the Kaplan-Meier method and compared with a log-rank test.To identify the patients who gained a survival benefit from surgical resection,we also investigated prognostic factors for survival following surgical resection.Multivariate analyses of the prognostic factors for survival were performed using the Cox proportional hazard model. RESULTS:The overall survival(OS)rate was significantly higher in the surgical resection group than in the TACE group(48.1%vs 28.9%at 5 years,P<0.005). LT had the best OS rate,which was better than that of the surgical resection group,although the difference was not statistically significant(80.2%vs 48.1%at 5 years,P=0.447).The disease-free survival rates were also significantly higher in the LT group than in the surgical resection group(88.2%vs 11.2%at 5 years, P<0.001).Liver cirrhosis was the only significant prognostic factor for poor OS after surgical resection. Clinical liver cirrhosis rates were 55.6%(20/36)in the resection group and 93.5%(100/107)in the TACE group.There were 19 major and 17 minor resections. En bloc resection was performed in 23 patients,multisite resection was performed in 5 patients,and combined resection with RFA was performed in 8 patients. In the TACE group,only 34 patients(31.8%)were recorded as having complete remission after primary TACE.Seventy-two patients(67.3%)were retreated with repeated TACE combined with other therapies. In patients who underwent surgical resection,the 16 patients who did not have cirrhosis had higher 5-year OS and disease-free survival rates than the 20 patients who had cirrhosis(80.8%vs 25.5%5-year OS rate, P=0.006;22.2%vs 0%5-year disease-free survival rate,P=0.048).Surgical resection in the 20 patients who had cirrhosis did not provide any survival benefit when compared with TACE(25.5%vs 24.7%5-year OS rate,P=0.225).Twenty-nine of the 36 patients who underwent surgical resection experienced recur-rence.Of the patients with cirrhosis,80%(16/20) were within the Milan criteria at the time of recurrence CONCLUSION:Among patients with two or three HCCs, no radiologic vascular invasion,and tumor diameters≤ 5 cm,surgical resection is recommended only in those without cirrhosis.

Treatment outcome of localized Helicobacter pylori-negative low-grade gastric MALT lymphoma

AIM: To investigate treatment outcome of Helicobacter pylori (H.pylori )-negative low-grade gastric mucosaassociated lymphoid tissue (MALT) lymphoma.METHODS: In this study,we retrospectively reviewed the clinical outcome and clinicopathologic factors of stage Ⅰ E H.pylori -negative low-grade gastric MALT lymphoma cases from August 1998 to June 2009.RESULTS: A total of eleven patients with H.pylori -negative low-grade gastric MALT lymphoma were enrolled in the study and received anti-H.pylori eradication treatment and/or radiotherapy or excisional therapy.Complete remission (CR) of gastric MALT lymphoma was achieved in all patients.The time to CR was 1-66 mo (median,1 mo).CONCLUSION: Eradication therapy may be offered as an initial treatment option even in cases of localized H.pylori -negative gastric MALT lymphoma.

Overexpression of miR-196b and HOXA10 characterize a poor-prognosis gastric cancer subtype

AIM:To identify molecular biologic differences between two gastric adenocarcinoma subgroups presenting different prognoses through the analysis of microRNA and protein expression.METHODS:Array technologies were used to generate1146 microRNAs and 124 proteins expression profiles of samples from 60 patients with gastric cancer.For the integrative analysis,we used established mRNA expression data published in our previous study.Whole mRNA expression levels were acquired from microarray data for 60 identical gastric cancer patients.Two gastric adenocarcinoma subgroups with distinct mRNA expression profiles presented distinctly different prognoses.MicroRNA and protein expression patterns were compared between gastric cancer tissue and normal gastric tissue and between two different prognostic groups.Aberrantly expressed microRNA,associated mRNA,and protein in patients with poor-prognosis gastric cancer were validated by quantitative reverse transcription polymerase chain reaction and immunochemistry in independent patients.RESULTS:We obtained the expression data of 1146microRNAs and 124 cancer-related proteins.Four microRNAs were aberrantly expressed in the two prognostic groups and in cancer vs non-cancer tissues(P<0.05).In the poor-prognosis group,miR-196b,miR-135b,and miR-93 were up-regulated and miR-29c*was down-regulated.miR-196b expression positively correlated with Homeobox A10(HOXA10)expression(r=0.726,P<0.001),which was significantly increased in poor-prognosis patients(P<0.001).Comparing gastric cancer with non-cancer tissues,46/124 proteins showed differential expression(P<0.05);COX2(P<0.001)and cyclin B1(P=0.017)were clearly overexpressed in the poor-prognosis group.CONCLUSION:Co-activation of miR-196b and HOXA10characterized a poor-prognosis subgroup of patients with gastric cancer.Elucidation of the biologic function of miR-196b and HOXA10 is warranted.