Bacterial infections are common in cirrhotic patients with acute variceal bleeding,occurring in 20%within48 h.Outcomes including early rebleeding and failure to control bleeding are strongly associated with bacterial ...Bacterial infections are common in cirrhotic patients with acute variceal bleeding,occurring in 20%within48 h.Outcomes including early rebleeding and failure to control bleeding are strongly associated with bacterial infection.However,mortality from variceal bleeding is largely determined by the severity of liver disease.Besides a higher Child-Pugh score,patients with hepatocellular carcinoma are particularly susceptible to infections.Despite several hypotheses that include increased use of instruments,greater risk of aspiration pneumonia and higher bacterial translocation,it remains debatable whether variceal bleeding results in infection or vice versa but studies suggest that antibiotic prophylaxis prior to endoscopy and up to 8 h is useful in reducing bacteremia and spontaneous bacterial peritonitis.Aerobic gram negative bacilli of enteric origin are most commonly isolated from cultures,but more recently,gram positives and quinolone-resistant organisms are increasingly seen,even though their clinical significance is unclear.Fluoroquinolones(including ciprofloxacin and norfloxacin)used for short term(7 d)have the most robust evidence and are recommended in most expert guidelines.Short term intravenous cephalosporin(especially ceftriaxone),given in a hospital setting with prevalent quinolone-resistant organisms,has been shown in studies to be beneficial,particularly in high risk patients with advanced cirrhosis.展开更多
Colorectal cancer (CRC) is a major global health concern. Accumulation of cancer-associated fibroblasts(CAFs) in CRC is associated with poor prognosis and disease recurrence. CAFs are the main cellular component ofthe...Colorectal cancer (CRC) is a major global health concern. Accumulation of cancer-associated fibroblasts(CAFs) in CRC is associated with poor prognosis and disease recurrence. CAFs are the main cellular component ofthe tumor microenvironment. CAF-tumor cell interplay, which is facilitated by various secretomes, drives colorectalcarcinogenesis. The complexity of CAF populations contributes to the heterogeneity of CRC and influences patientsurvival and treatment response. Due to their significant roles in colorectal carcinogenesis, different clinicalapplications utilizing or targeting CAFs have been suggested. Circulating CAFs (cCAFs) which can be detected inblood samples, have been proposed to help in determining patient prognosis and enables the detection of cancerthrough liquid biopsy. Liquid biopsy is gaining traction as it is non-invasive, allows frequent and easy sampling, andshows concordance to tissue biopsy analysis. In addition, CAF-targeted therapy is currently being studied extensivelyto be used as one of the treatment avenues for CRC. Various mechanisms of CAF-targeted therapy have beenreported, including blocking the signaling pathways involving CAFs and cancer cells, thus abolishing the CAF-tumorcell crosstalk and subsequently hindering tumorigenesis. These translational applications of cCAFs and utilization ofCAFs as key targets for CRC therapy, although still in the early phases of development, will potentially improve CRCpatient management in the future.展开更多
AIM: To identify genes associated with gastric pre-cancerous lesions in Helicobacter pylori (H. pylori )susceptible ethnic Malays. METHODS: Twenty-three Malay subjects with H. pylori infection and gastric precancerous...AIM: To identify genes associated with gastric pre-cancerous lesions in Helicobacter pylori (H. pylori )susceptible ethnic Malays. METHODS: Twenty-three Malay subjects with H. pylori infection and gastric precancerous lesions identified during endoscopy were included as "cases". Thirtyseven Malay subjects who were H. pylori negative and had no precancerous lesions were included as "controls". Venous blood was collected for genotyping with Affymetrix 50K Xba1 kit. Genotypes with call rates < 90% for autosomal single nucleotide polymorphisms (SNPs) were excluded. For each precancerous lesion, associated SNPs were identified from Manhattan plots, and only SNPs with a χ2 P value < 0.05 and Hardy Weinberg Equilibrium P value > 0.5 was considered as significant markers. RESULTS: Of the 23 H. pylori -positive subjects recruited, one sample was excluded from further analysis due to a low genotyping call rate. Of the 22 H. pylori positive samples, atrophic gastritis only was present in 50.0%, complete intestinal metaplasia was present in 18.25%, both incomplete intestinal metaplasia and dysplasia was present in 22.7%, and dysplasia only was present in 9.1%. SNPs rs9315542 (UFM1 gene), rs6878265 (THBS4 gene), rs1042194 (CYP2C19 gene) and rs10505799 (MGST1 gene) were significantly associated with atrophic gastritis, complete intestinal metaplasia, incomplete metaplasia with foci of dysplasia and dysplasia, respectively. Allele frequencies in "cases" vs "controls" for rs9315542, rs6878265, rs1042194 and rs10505799 were 0.4 vs 0.06, 0.6 vs 0.01, 0.6 vs 0.01 and 0.5 vs 0.02, respectively. CONCLUSION: Genetic variants possibly related to gastric precancerous lesions in ethnic Malays susceptible to H. pylori infection were identified for testing in subsequent trials.展开更多
AIM:To survey irritable bowel syndrome(IBS) using Rome Ⅲ criteria among Malays from the north-eastern region of Peninsular Malaysia.METHODS:A previously validated Malay language Rome Ⅲ IBS diagnostic questionnaire w...AIM:To survey irritable bowel syndrome(IBS) using Rome Ⅲ criteria among Malays from the north-eastern region of Peninsular Malaysia.METHODS:A previously validated Malay language Rome Ⅲ IBS diagnostic questionnaire was used in the current study.A prospective sample of 232 Malay subjects(80% power) was initially screened.Using a stratified random sampling strategy,a total of 221 Malay subjects(112 subjects in a "full time job" and 109 subjects in "no full time job") were recruited.Subjects were visitors(friends and relatives) within the hospital compound and were representative of the local community.Red flags and psychosocial alarm symptoms were also assessed in the current study using previously translated and validated questionnaires.Subjects with IBS were sub-typed into constipation-predominant,diarrhea-predominant,mixed type and un-subtyped.Univariable and multivariable analyses were used to test for association between socioeconomic factors and presence of red flags and psychosocial alarm features among the Malays with IBS.RESULTS:IBS was present in 10.9%(24/221),red flags in 22.2%(49/221) and psychosocial alarm features in 9.0%(20/221).Red flags were more commonly reported in subjects with IBS(83.3%) than psychosocial alarm features(20.8%,P < 0.001).Subjects with IBS were older(mean age 41.4 years vs 36.9 years,P = 0.08),but no difference in gender was noted(P = 0.4).Using univariable analysis,IBS was significantly associated with a tertiary education,high individual income above RM1000,married status,exsmoker and the presence of red flags(all P < 0.05).In multiple logistic regression analysis,only the presence of red flags was significantly associated with IBS(odds ratio:0.02,95%CI:0.004-0.1,P < 0.001).The commonest IBS sub-type was mixed type(58.3%),followed by constipation-predominant(20.8%),diarrheapredominant(16.7%) and un-subtyped(4.2%).Four of 13 Malay females(30.8%) with IBS also had menstrual pain.Most subjects with IBS had at least one red flag(70.8%),12.5% had two red flags and 16.7% with no red flags.The commonest red flag was a bowel habit change in subjects > 50 years old and this was reported by 16.7% of subjects with IBS.CONCLUSION:Using the Rome Ⅲ criteria,IBS was common among ethnic Malays from the north-eastern region of Peninsular Malaysia.展开更多
Helicobacter pylori(H. pylori) is an important cause for gastric cancer in high risk individuals. H. pylori colonizes more than 50% of the world's population and associated peptic ulcer disease and gastric maligna...Helicobacter pylori(H. pylori) is an important cause for gastric cancer in high risk individuals. H. pylori colonizes more than 50% of the world's population and associated peptic ulcer disease and gastric malignancy have important public health implications. It has been classified as a class Ⅰ carcinogen in 1994 by the World Health Organization. Clinicians are often prompted to eliminate the infection the moment it is detected. This also, unfortunately, led to reckless use of antibiotics and reports of increasing resistance are now worldwide. Each year, many of people die from gastric cancer; thus application of effective vaccine can reduce this relatively high mortality worldwide. H. pylori can be eliminated by antibiotics but efficacy is sharply decreasing. Moreover, current therapy is also expensive and with side effects. Vaccine may be the best solution to the above problem but there are many challenges in producing such an effective therapeutic vaccine. Recently, the Chinese group published in Lancet, a single-center, randomized, phase Ⅲ study of an oral recombinant vaccine(Urease B subunit fused with heat-labile enterotoxin B derived from Escherichia coli) prescribed in the Chinese children(6-15 years) without a history of H. pylori infection. This review provides an insight into this new solution for an old challenge.展开更多
BACKGROUND Major societies provide differing guidance on management of Barrett’s esophagus(BE),making standardization challenging.AIM To evaluate the preferred diagnosis and management practices of BE among Asian end...BACKGROUND Major societies provide differing guidance on management of Barrett’s esophagus(BE),making standardization challenging.AIM To evaluate the preferred diagnosis and management practices of BE among Asian endoscopists.METHODS Endoscopists from across Asia were invited to participate in an online questionnaire comprising eleven questions regarding diagnosis,surveillance and management of BE.RESULTS Five hundred sixty-nine of 1016(56.0%)respondents completed the survey,with most respondents from Japan(n=310,54.5%)and China(n=129,22.7%).Overall,the preferred endoscopic landmark of the esophagogastric junction was squamocolumnar junction(42.0%).Distal palisade vessels was preferred in Japan(59.0%vs 10.0%,P<0.001)while outside Japan,squamo-columnar junction was preferred(59.5%vs 27.4%,P<0.001).Only 16.3%of respondents used Prague C and M criteria all the time.It was never used by 46.1%of Japanese,whereas 84.2%outside Japan,endoscopists used it to varying extents(P<0.001).Most Asian endoscopists(70.8%)would survey long-segment BE without dysplasia every two years.Adherence to Seattle protocol was poor with only 6.3%always performing it.73.2%of Japanese never did it,compared to 19.3%outside Japan(P<0.001).The most preferred(74.0%)treatment of non-dysplastic BE was proton pump inhibitor only when the patient was symptomatic or had esophagitis.For BE with low-grade dysplasia,6-monthly surveillance was preferred in 61.9%within Japan vs 47.9%outside Japan(P<0.001).CONCLUSION Diagnosis and management of BE varied within Asia,with stark contrast between Japan and outside Japan.Most Asian endoscopists chose squamo-columnar junction to be the landmark for esophagogastric junction,which is incorrect.Most also did not consistently use Prague criteria,and Seattle protocol.Lack of standardization,education and research are possible reasons.展开更多
Background There is increasing evidence that CT pulmonary arteriography and venography allow a better diagnostic yield for deep vein thrombosis （DVT） in suspected acute pulmonary embolism （PE）. The aim was to inve...Background There is increasing evidence that CT pulmonary arteriography and venography allow a better diagnostic yield for deep vein thrombosis （DVT） in suspected acute pulmonary embolism （PE）. The aim was to investigate the value for using such an approach in a multiracial Asian population. Methods A total of 135 consecutive subjects with clinically suspected PE in various clinical settings （postoperative in 23 subjects） were referred and evaluated for venous thromboemboUsm using CT pulmonary arteriography and venography in a tertiary hospital, Malaysia. The distribution of DVT was assessed based on the frequency rate of thrombosis in a particular anatomical region （inferior vena cava, pelvic, femoral and popliteal）. Results In 130 subjects, excluding 5 subjects having poor images, both DVT and PE were detected in 11.5% （15/130） subjects and DVT alone was detected in 6.9% （9/130） subjects giving a combined rate of venous thromboembolism of 18.4%. A history of malignancy was significantly associated with positive scans, P=0.02. It was found that left pelvic veins （18.2%） and left femoral veins （19.5%） were more commonly thrombosed in this population. Conclusion CT pulmonary arteriography and venography is a useful technique in the evaluation of venous thromboembolism in a multi-racial Asian population.展开更多
文摘Bacterial infections are common in cirrhotic patients with acute variceal bleeding,occurring in 20%within48 h.Outcomes including early rebleeding and failure to control bleeding are strongly associated with bacterial infection.However,mortality from variceal bleeding is largely determined by the severity of liver disease.Besides a higher Child-Pugh score,patients with hepatocellular carcinoma are particularly susceptible to infections.Despite several hypotheses that include increased use of instruments,greater risk of aspiration pneumonia and higher bacterial translocation,it remains debatable whether variceal bleeding results in infection or vice versa but studies suggest that antibiotic prophylaxis prior to endoscopy and up to 8 h is useful in reducing bacteremia and spontaneous bacterial peritonitis.Aerobic gram negative bacilli of enteric origin are most commonly isolated from cultures,but more recently,gram positives and quinolone-resistant organisms are increasingly seen,even though their clinical significance is unclear.Fluoroquinolones(including ciprofloxacin and norfloxacin)used for short term(7 d)have the most robust evidence and are recommended in most expert guidelines.Short term intravenous cephalosporin(especially ceftriaxone),given in a hospital setting with prevalent quinolone-resistant organisms,has been shown in studies to be beneficial,particularly in high risk patients with advanced cirrhosis.
基金supported by the Ministry of Higher Education Malaysia for Fundamental Research Grant Scheme with Project Code:FRGS/1/2020/SKK0/USM/03/10 and USM.
文摘Colorectal cancer (CRC) is a major global health concern. Accumulation of cancer-associated fibroblasts(CAFs) in CRC is associated with poor prognosis and disease recurrence. CAFs are the main cellular component ofthe tumor microenvironment. CAF-tumor cell interplay, which is facilitated by various secretomes, drives colorectalcarcinogenesis. The complexity of CAF populations contributes to the heterogeneity of CRC and influences patientsurvival and treatment response. Due to their significant roles in colorectal carcinogenesis, different clinicalapplications utilizing or targeting CAFs have been suggested. Circulating CAFs (cCAFs) which can be detected inblood samples, have been proposed to help in determining patient prognosis and enables the detection of cancerthrough liquid biopsy. Liquid biopsy is gaining traction as it is non-invasive, allows frequent and easy sampling, andshows concordance to tissue biopsy analysis. In addition, CAF-targeted therapy is currently being studied extensivelyto be used as one of the treatment avenues for CRC. Various mechanisms of CAF-targeted therapy have beenreported, including blocking the signaling pathways involving CAFs and cancer cells, thus abolishing the CAF-tumorcell crosstalk and subsequently hindering tumorigenesis. These translational applications of cCAFs and utilization ofCAFs as key targets for CRC therapy, although still in the early phases of development, will potentially improve CRCpatient management in the future.
基金Supported by Fundamental Research Grant Scheme(FRGS)203/PPSP/6171121,1001/PPSP/812016 and 1001/PPSP/8122022 of Universiti Sains MalaysiaThe National Science Foundation of China grants,No.30971577and No.31171218+5 种基金the Shanghai Rising-Star Program,No.11QA1407600the Science Foundation of the Chinese Academy of Sciences(CAS)(KSCX2-EW-Q-1-11KSCX2-EW-R-01-05KSCX2-EW-J-15-05)the support of the National Program for Top-notch Young Innovative Talentsthe support of K.C. Wong Education Foundation, Hong Kong
文摘AIM: To identify genes associated with gastric pre-cancerous lesions in Helicobacter pylori (H. pylori )susceptible ethnic Malays. METHODS: Twenty-three Malay subjects with H. pylori infection and gastric precancerous lesions identified during endoscopy were included as "cases". Thirtyseven Malay subjects who were H. pylori negative and had no precancerous lesions were included as "controls". Venous blood was collected for genotyping with Affymetrix 50K Xba1 kit. Genotypes with call rates < 90% for autosomal single nucleotide polymorphisms (SNPs) were excluded. For each precancerous lesion, associated SNPs were identified from Manhattan plots, and only SNPs with a χ2 P value < 0.05 and Hardy Weinberg Equilibrium P value > 0.5 was considered as significant markers. RESULTS: Of the 23 H. pylori -positive subjects recruited, one sample was excluded from further analysis due to a low genotyping call rate. Of the 22 H. pylori positive samples, atrophic gastritis only was present in 50.0%, complete intestinal metaplasia was present in 18.25%, both incomplete intestinal metaplasia and dysplasia was present in 22.7%, and dysplasia only was present in 9.1%. SNPs rs9315542 (UFM1 gene), rs6878265 (THBS4 gene), rs1042194 (CYP2C19 gene) and rs10505799 (MGST1 gene) were significantly associated with atrophic gastritis, complete intestinal metaplasia, incomplete metaplasia with foci of dysplasia and dysplasia, respectively. Allele frequencies in "cases" vs "controls" for rs9315542, rs6878265, rs1042194 and rs10505799 were 0.4 vs 0.06, 0.6 vs 0.01, 0.6 vs 0.01 and 0.5 vs 0.02, respectively. CONCLUSION: Genetic variants possibly related to gastric precancerous lesions in ethnic Malays susceptible to H. pylori infection were identified for testing in subsequent trials.
基金Supported by Malaysian Society of Gastroenterology and Hepatology Research Award 2008
文摘AIM:To survey irritable bowel syndrome(IBS) using Rome Ⅲ criteria among Malays from the north-eastern region of Peninsular Malaysia.METHODS:A previously validated Malay language Rome Ⅲ IBS diagnostic questionnaire was used in the current study.A prospective sample of 232 Malay subjects(80% power) was initially screened.Using a stratified random sampling strategy,a total of 221 Malay subjects(112 subjects in a "full time job" and 109 subjects in "no full time job") were recruited.Subjects were visitors(friends and relatives) within the hospital compound and were representative of the local community.Red flags and psychosocial alarm symptoms were also assessed in the current study using previously translated and validated questionnaires.Subjects with IBS were sub-typed into constipation-predominant,diarrhea-predominant,mixed type and un-subtyped.Univariable and multivariable analyses were used to test for association between socioeconomic factors and presence of red flags and psychosocial alarm features among the Malays with IBS.RESULTS:IBS was present in 10.9%(24/221),red flags in 22.2%(49/221) and psychosocial alarm features in 9.0%(20/221).Red flags were more commonly reported in subjects with IBS(83.3%) than psychosocial alarm features(20.8%,P < 0.001).Subjects with IBS were older(mean age 41.4 years vs 36.9 years,P = 0.08),but no difference in gender was noted(P = 0.4).Using univariable analysis,IBS was significantly associated with a tertiary education,high individual income above RM1000,married status,exsmoker and the presence of red flags(all P < 0.05).In multiple logistic regression analysis,only the presence of red flags was significantly associated with IBS(odds ratio:0.02,95%CI:0.004-0.1,P < 0.001).The commonest IBS sub-type was mixed type(58.3%),followed by constipation-predominant(20.8%),diarrheapredominant(16.7%) and un-subtyped(4.2%).Four of 13 Malay females(30.8%) with IBS also had menstrual pain.Most subjects with IBS had at least one red flag(70.8%),12.5% had two red flags and 16.7% with no red flags.The commonest red flag was a bowel habit change in subjects > 50 years old and this was reported by 16.7% of subjects with IBS.CONCLUSION:Using the Rome Ⅲ criteria,IBS was common among ethnic Malays from the north-eastern region of Peninsular Malaysia.
文摘Helicobacter pylori(H. pylori) is an important cause for gastric cancer in high risk individuals. H. pylori colonizes more than 50% of the world's population and associated peptic ulcer disease and gastric malignancy have important public health implications. It has been classified as a class Ⅰ carcinogen in 1994 by the World Health Organization. Clinicians are often prompted to eliminate the infection the moment it is detected. This also, unfortunately, led to reckless use of antibiotics and reports of increasing resistance are now worldwide. Each year, many of people die from gastric cancer; thus application of effective vaccine can reduce this relatively high mortality worldwide. H. pylori can be eliminated by antibiotics but efficacy is sharply decreasing. Moreover, current therapy is also expensive and with side effects. Vaccine may be the best solution to the above problem but there are many challenges in producing such an effective therapeutic vaccine. Recently, the Chinese group published in Lancet, a single-center, randomized, phase Ⅲ study of an oral recombinant vaccine(Urease B subunit fused with heat-labile enterotoxin B derived from Escherichia coli) prescribed in the Chinese children(6-15 years) without a history of H. pylori infection. This review provides an insight into this new solution for an old challenge.
文摘BACKGROUND Major societies provide differing guidance on management of Barrett’s esophagus(BE),making standardization challenging.AIM To evaluate the preferred diagnosis and management practices of BE among Asian endoscopists.METHODS Endoscopists from across Asia were invited to participate in an online questionnaire comprising eleven questions regarding diagnosis,surveillance and management of BE.RESULTS Five hundred sixty-nine of 1016(56.0%)respondents completed the survey,with most respondents from Japan(n=310,54.5%)and China(n=129,22.7%).Overall,the preferred endoscopic landmark of the esophagogastric junction was squamocolumnar junction(42.0%).Distal palisade vessels was preferred in Japan(59.0%vs 10.0%,P<0.001)while outside Japan,squamo-columnar junction was preferred(59.5%vs 27.4%,P<0.001).Only 16.3%of respondents used Prague C and M criteria all the time.It was never used by 46.1%of Japanese,whereas 84.2%outside Japan,endoscopists used it to varying extents(P<0.001).Most Asian endoscopists(70.8%)would survey long-segment BE without dysplasia every two years.Adherence to Seattle protocol was poor with only 6.3%always performing it.73.2%of Japanese never did it,compared to 19.3%outside Japan(P<0.001).The most preferred(74.0%)treatment of non-dysplastic BE was proton pump inhibitor only when the patient was symptomatic or had esophagitis.For BE with low-grade dysplasia,6-monthly surveillance was preferred in 61.9%within Japan vs 47.9%outside Japan(P<0.001).CONCLUSION Diagnosis and management of BE varied within Asia,with stark contrast between Japan and outside Japan.Most Asian endoscopists chose squamo-columnar junction to be the landmark for esophagogastric junction,which is incorrect.Most also did not consistently use Prague criteria,and Seattle protocol.Lack of standardization,education and research are possible reasons.
文摘Background There is increasing evidence that CT pulmonary arteriography and venography allow a better diagnostic yield for deep vein thrombosis （DVT） in suspected acute pulmonary embolism （PE）. The aim was to investigate the value for using such an approach in a multiracial Asian population. Methods A total of 135 consecutive subjects with clinically suspected PE in various clinical settings （postoperative in 23 subjects） were referred and evaluated for venous thromboemboUsm using CT pulmonary arteriography and venography in a tertiary hospital, Malaysia. The distribution of DVT was assessed based on the frequency rate of thrombosis in a particular anatomical region （inferior vena cava, pelvic, femoral and popliteal）. Results In 130 subjects, excluding 5 subjects having poor images, both DVT and PE were detected in 11.5% （15/130） subjects and DVT alone was detected in 6.9% （9/130） subjects giving a combined rate of venous thromboembolism of 18.4%. A history of malignancy was significantly associated with positive scans, P=0.02. It was found that left pelvic veins （18.2%） and left femoral veins （19.5%） were more commonly thrombosed in this population. Conclusion CT pulmonary arteriography and venography is a useful technique in the evaluation of venous thromboembolism in a multi-racial Asian population.
