A new look at anti-Helicobacter pylori therapy

With the rising prevalence of antimicrobial resistance,the treatment success of standard triple therapy has recently declined to unacceptable levels (i.e.,80% or less) in most countries.Therefore,several treatment regimens have emerged to cure Helicobacter pylori (H.pylori) infection.Novel first-line anti-H.pylori therapies in 2011 include sequential therapy,concomitant quadruple therapy,hybrid (dual-concomitant) therapy and bismuth-containing quadruple therapy.After the failure of standard triple therapy,a bismuth-containing quadruple therapy comprising a proton pump inhibitor (PPI),bismuth,tetracycline and metronidazole can be employed as rescue treatment.Recently,triple therapy combining a PPI,levofloxacin and amoxicillin has been proposed as an alternative to the standard rescue therapy.This salvage regimen can achieve a higher eradication rate than bismuth-containing quadruple therapy in some regions and has less adverse effects.The best second-line therapy for patients who fail to eradicate H.pylori with first-line therapies containing clarithromycin,amoxicillin and metronidazole is unclear.However,a levofloxacin-based triple therapy is an accepted rescue treatment.Most guidelines suggest that patients requiring third-line therapy should be referred to a medical center and treated according to the antibiotic susceptibility test.Nonetheless,an empirical therapy (such as levofloxacin-based or furazolidone-based therapies) can be employed to terminate H.pylori infection if antimicrobial sensitivity data are unavailable.

Reappraisal of endoscopic papillary balloon dilation for the management of common bile duct stones

Although endoscopic sphincterotomy(EST) is still considered as a gold standard treatment for common bile duct(CBD) stones in western guideline, endoscopic papillary balloon dilation(EPBD) is commonly used by the endoscopists in Asia as the first-line treatment for CBD stones. Besides the advantages of a technical easy procedure, endoscopic papillary large balloon dilation(EPLBD) can facilitate the removal of large CBD stones.The indication of EPBD is now extended from removal of the small stones by using traditional balloon, to removal of large stones and avoidance of lithotripsy by using large balloon alone or after EST. According to the reports of antegrade papillary balloon dilatation, balloon dilation itself is not the cause of pancreatitis. On the contrary, adequate dilation of papillary orifice can reduce the trauma to the papilla and pancreas by the basket or lithotripter during the procedure of stone extraction. EPLBD alone is as effective as EPLBD with limited EST. Longer ballooning time may be beneficial in EPLBD alone to achieve adequate loosening of papillary orifice. The longer ballooning time does not increase the risk of pancreatitis but may reduce the bleeding episodes in patients with coagulopathy. Slowly inflation of the balloon, but not exceed the diameter of bile duct and tolerance of the patients are important to prevent the complication of perforation. EPBLD alone or with EST are not the sphincter preserved procedures, regular follow up is necessary for early detection and management of CBD stones recurrence.

Second-line rescue treatment of Helicobacter pylori infection: Where are we now?

At present, the best rescue therapy for Helicobacter pylori(H. pylori) infection following failure of firstline eradication remains unclear. The Maastricht Ⅴ/Florence Consensus Report recommends bismuth quadruple therapy, or fluoroquinolone-amoxicillin triple/quadruple therapy as the second-line therapy for H. pylori infection. Meta-analyses have shown that bismuth quadruple therapy and levofloxacin-amoxicillin triple therapy have comparable eradication rates, while the former has more adverse effects than the latter. There are no significant differences between the eradication rates of levofloxacin-amoxicillin triple and quadruple therapies. However, the eradication rates of both levofloxacin-containing treatments are suboptimal. An important caveat of levofloxacin-amoxicillin triple or quadruple therapy is poor eradication efficacy in the presence of fluoroquinolone resistance. High-dose dual therapy is an emerging second-line therapy and has an eradication efficacy comparable with levofloxacinamoxicillin triple therapy. Recently, a 10-d tetracyclinelevofloxacin(TL) quadruple therapy comprised of a proton pump inhibitor, bismuth, tetracycline and levofloxacin has been developed, which achieves a markedly higher eradication rate compared with levofloxacin-amoxicillin triple therapy(98% vs 69%) in patients with failure of standard triple, bismuth quadruple or non-bismuth quadruple therapy. The present article reviews current second-line anti-H. pylori regimens and treatment algorisms. In conclusion, bismuth quadruple therapy, levofloxacin-amoxicillin triple/quadruple therapy, high-dose dual therapy and TL quadruple therapy can be used as second-line treatment for H. pylori infection. Current evidence suggests that 10-d TL quadruple therapy is a simple and effective regimen, and has the potential to become a universal rescue treatment following eradication failure by all firstline eradication regimens for H. pylori infection.

Hybrid therapy for Helicobacter pylori infection:A systemic review and meta-analysis

AIM: To compare the effectiveness of hybrid therapy with other recommended regimens using metaanalysis.METHODS: Bibliographical searches for randomized trials comparing hybrid and other therapies were performed in Pubmed, the Cochrane Library and relevant congresses up to February 2015 using the following keywords(all fields and/or me SH):("Helicobacter pylori " or "H. pylori") and("hybrid therapy" or "sequential-concomitant therapy"). metaanalyses were performed with Cochrane Review manager 5.1. The random effect model proposed by Der Simonian and Laird and the mantel-Haenszel method were used to estimate the pooled relative risk and 95%CI of the efficacy outcomes between hybrid therapy and other eradication therapies. RESULTS: Eight studies(2516 subjects) met entry criteria. The antimicrobial resistance in the study groups ranged from 6.9% to 23.5%. The mean cure rates of hybrid therapy by intention-to-treat(ITT) and perprotocol analyses were 88.5%(n = 1207; range: 80.0% to 97.4%) and 93.3%(n = 1109; range: 85.7% to99.1%), respectively. meta-analysis showed there was no significant difference in ITT eradication rate between hybrid and sequential therapy(relative risk: 1.01; 95%CI: 0.92-1.11). Subgroup analysis revealed hybrid therapy was more effective than sequential therapy in the non-Italian populations(95%CI: 1.01-1.18) and was only less effective in one, Italian population(95%CI: 0.83-0.98). There was no significant difference in eradication rate between hybrid therapy and concomitant therapy(95%CI: 0.93-1.02). No head-tohead comparisons of hybrid therapy and standard triple therapy or bismuth quadruple therapy were found. However, a multicenter, randomized trial showed that reverse hybrid therapy was superior to standard triple therapy(95.5% vs 88.6% ITT; P = 0.011).CONCLUSION: Hybrid therapy appears to be an effective, safe, and well-tolerated treatment for H. pylori infection in the era of increasing antibiotic resistance.

Gastric juice acidity in upper gastrointestinal diseases

AIM: To search the independent factors determining gastric juice acidity and to investigate the acidity of gastric juices in various benign and malignant upper gastrointestinal diseases. METHODS: Fasting gastric juice acidity of 165 healthysubjects and 346 patients with esophageal ulcer (n = 21), gastric ulcer (n = 136), duodenal ulcer (n = 100) or gastric cancer (n = 89) were measured and compared. Additionally, gastric specimens were taken from the antrum and body for rapid urease test and histological examination. RESULTS: Multivariate analysis revealed that bile stain of gastric juice, high acute inflammatory score of the corpus, and atrophy of the corpus were independent risk factors for the development of gastric hypoacidity with odds ratios of 3.1 (95% CI: 1.3-7.3), 3.1 (95% CI: 1.2-7.9) and 3.5 (95% CI: 1.3-9.2). Esophageal ulcer and duodenal ulcer patients had a lower pH level (1.9 and 2.1 vs 2.9, both P < 0.05) of gastric juices than healthy subjects. In contrast, gastric ulcer and gastric cancer patients had a higher pH level (3.4 and 6.6 vs 2.9, both P < 0.001) than healthy controls. Hypoacidity existed in 22%, 5%, 29%, 5% and 88% of healthy subjects, esophageal ulcer, gastric ulcer, duodenal ulcer and gastric cancer patients, respectively. CONCLUSION: Bile reflux, atrophy and dense neutrophil infiltrate of the corpus are three independent factors determining the acidity of gastric juice.

Composition of common bile duct stones in Chinese patients during and after endoscopic sphincterotomy

AIM: Endoscopic sphincterotomy (ES) is a well-established therapeutic modality for the removal of common bile duct (CBD) stones. After ES there are still around 10% of patients that experience recurrent CBD stones. The aim of this study is to investigate the composition of CBD stones before and after ES and its clinical significance in Chinese patients.METHODS: From January 1996 to December 2003, 735Veterans General Hospital and stone specimens from 266patients were sent for analysis. Seventy-five patients had recurrent CBD stones and stone specimens from 44patients were sent for analysis. The composition of the stones was analyzed by infrared (IR) spectrometry and they were classified as cholesterol or bilirubinate stones according to the predominant composition. Clinical data were analyzed.RESULTS: In the initial 266 stone samples, 217 (82%)were bilirubinate stones, 42 (16%) were cholesterol stones,3 were calcium carbonate stones, 4 were mixed cholesterol and bilirubinate stones. Patients with bilirubinate stones were significantly older than patients with cholesterol stones (66±13 years vs 56±17 years, P= 0.001). In the 44 recurrent stone samples, 38 (86%) were bilirubinate stones, 3 (7%) were cholesterol stones, and 3 were mixed cholesterol and bilirubinate stones. In 27 patients, bothinitial and recurrent stone specimens can be obtained,23 patients had bilirubinate stones initially and 2 became cholesterol stones in the recurrent attack. In the four patients with initial cholesterol stones, three patients had bilirubinate stones and one patient had a cholesterol stone in the recurrent attack.CONCLUSION: Bilirubinate stone is the predominant composition of initial or recurrent CBD stone in Chinese patients. The composition of CBD stones may be different from initial stones after ES.

Prevalence and risk factors for Barrett’s esophagus in Taiwan

BACKGROUND Barrett’s esophagus(BE)is a pre-malignant condition associated with the development of esophageal adenocarcinoma.The prevalence of BE in the general populations of Asian countries ranges from 0.06%to 1%.However,with lifestyle changes in Asian countries and adoption of western customs,the prevalence of BE might have increased.AIM To determine the current prevalence of BE in Taiwan,and to investigate risk factors predicting the presence of BE.METHODS This retrospective study was conducted at the Health Evaluation Center of Kaohsiung Veterans General Hospital in Taiwan.Between January 2015 and December 2015,3385 subjects undergoing routine esophagogastroduodenoscopy examinations as part of a health check-up at the Health Evaluation Center were included.Patient characteristics and endoscopic findings were carefully reviewed.Lesions with endoscopic findings consistent with BE awaiting histological evaluation were judged as endoscopically suspected esophageal metaplasia(ESEM).BE was defined based on extension of the columnar epithelium≥1 cm above the gastroesophageal junction and was confirmed based on the presence of specialized intestinal metaplasia(IM)in the metaplastic esophageal epithelium.Clinical factors of subjects with BE and subjects without BE were compared,and the risk factors predicting BE were analyzed.RESULTS A total of 3385 subjects(mean age,51.29±11.42 years;57.1%male)were included in the study,and 89 among them were confirmed to have IM and presence of goblet cells via biopsy examination.The majority of these individuals were classified as short segment BE(n=85).The overall prevalence of BE was 2.6%.Multivariate analysis disclosed that old age[odds ratio(OR)=1.033;95%confidence interval(CI):1.012-1.055;P=0.002],male gender(OR=2.106;95%CI:1.145-3.872;P=0.017),ingestion of tea(OR=1.695;95%CI:1.043-2.754;P=0.033),and presence of hiatal hernia(OR=3.037;95%CI:1.765-5.225;P<0.001)were significant risk factors predicting BE.The independent risk factor for the presence of IM in ESEM lesions was old age alone(OR=1.029;95%CI:1.006-1.053;P=0.014).CONCLUSION Current prevalence of BE among the general population in Taiwan is 2.6%.Old age,male gender,ingestion of tea and hiatal hernia are significant risk factors for BE.

Clinical application of dip-assisted endoscopic method for nasoenteric feeding in patients with gastroparesis and gastroesophageal wounds

AIM: To report the clinical experiences in the application of clip-assisted endoscopic method for nasoenteric feeeding in patients with gastroparesis and patients with gastroesophageal wounds, and to compare the efficacy of nasoenteric feeding in these two indications. METHODS: From April 2002 to January 2004, 21 consecutive patients with gastroparesis or gastroesophageal wounds were enrolled and received nasoenteric feeding for nutritional support. A clip-assisted method was used to place the nasoenteric tubes. Outcomes in the two groups were compared with respect to the successful rate of enteral feeding, percentage of recommended energyintake (REI), and complication rates.RESULTS: The gastroparesis group included 13 patients with major bums (n = 7), trauma (n = 2), congestive heart failure (n = 2) and post-surgery gastric stasis syndrome (n = 2). The esophageogastric wound group included eight patients with tracheoesophageal fistula (n = 2) and wound leakage following gastric surgery (n = 6). Two study groups were similar in feeding successful rates (84.6% vs75.0%). There were also no differences in the percentage of REI between groups (79.4% vs 78.6%). Additionally, no complications occurred in any of the study groups. CONCLUSION: Nasoenteric feeding is a useful method to provide nutritional support to most of the patients with gastroparesis who cannot tolerate nasogastric tube feeding and to the cases who need bypass feeding for esophageogastric wounds.

Implications of anti-parietal cell antibodies and anti-Helicobacter pylori antibodies in histological gastritis and patient outcome

AIM: To develop a serum or histological marker for early discovery of gastric atrophy or intestinal metaplasia. METHODS: This study enrolled 44 patients with gastric adenocarcinoma, 52 patients with duodenal ulcer, 14 patients with gastric ulcer and 42 consecutive healthy adults as controls. Each patient received an endoscopy and five biopsy samples were obtained. The degrees of histological parameters of gastritis were categorized following the Updated Sydney System. Anti-parietal cell antibodies (APCA) and anti-Helicobacter pylori (H pylori) antibodies (AHPA) were analyzed by immunoassays. H pylori infection was diagnosed by rapid urease test and histological examination. RESULTS: Patients with gastric cancer and gastric ulcer are significantly older than healthy subjects, while also displaying higher frequency of APCA than healthy controls. Patients with positive APCA showed higher scores in gastric atrophy and intestinal metaplasia of corpus than patients with negative APCA. Patients with positive AHPA had higher scores in gastric atrophy, intestinal metaplasia, and gastric inflammation of antrum than those patients with negative AHPA. Elderly patients had greater prevalence rates of APCA. Following multivariant logistic regression analysis, the only significant risk factor for antral atrophy is positive AHPA, while that for corpus atrophy is positive APCA. CONCLUSION: The existence of positive APCA correlates with glandular atrophy in corpus and the presence of positive AHPA correlates with glandular atrophy in antrum. The existence of serum APCA and AHPA betokens glandular atrophy and requires further examination for gastric cancer.

Prevalence and risk factors of asymptomatic peptic ulcer disease in Taiwan

AIM:To investigate the prevalence and risk factors of asymptomatic peptic ulcer disease(PUD)in a general Taiwan Residents population. METHODS:From January to August 2008,consecutive asymptomatic subjects undergoing a routine health check-up were evaluated by upper gastrointestinal endoscopy.Gastroduodenal mucosal breaks were carefully assessed,and a complete medical history and demographic data were obtained from each patient.Logistic regression analysis was conducted to identify indepen-dent risk factors for asymptomatic PUD. RESULTS:Of the 572 asymptomatic subjects,54(9.4%) were diagnosed as having PUD.The prevalence of gastric ulcer,duodenal ulcer and both gastric and duodenal ulcers were 4.7%,3.9%,and 0.9%,respectively. Multivariate analysis revealed that prior history of PUD [odds ratio(OR),2.0,95%CI:1.3-2.9],high body mass index[body mass index(BMI)25-30:OR,1.5,95%CI: 1.0-2.2;BMI>30 kg/m 2 :OR,3.6,95%CI:1.5-8.7] and current smoker(OR,2.6,95%CI:1.6-4.4)were independent predictors of asymptomatic PUD.In contrast, high education level was a negative predictor of PUD (years of education 10-12:OR,0.5,95%CI:0.3-0.8; years of education>12:OR,0.6,95%CI:0.3-0.9). CONCLUSION:The prevalence of PUD in asymptomatic subjects is 9.4%in Taiwan.Prior history of PUD, low education level,a high BMI and current smoker are independent risk factors for developing asymptomatic PUD.

Expression of altered retinoblastoma protein inversely correlates with tumor invasion in gastric carcinoma

AIM: To investigate the clinical and pathological significance of altered retinoblastoma (Rb) encoding protein (pRb) in gastric carcinoma. METHODS: Expression of altered pRb was analyzed in 91 patients with gastric adenocarcinoma by immunohistochemistry. RESULTS: Sixty-five percent (59/91) of the tumors were positively stained and the staining in tumor nuclei of gastric carcinoma ranged 0%-90%. Moreover, strong expression of altered pRb was found in 35% (6/17), 24% (5/21), 17% (8/46) and 0% (0/7) of T1, T2, T3 and T4 gastric carcinomas, respectively. altered pRb expression was inversely correlated with the depth of tumor invasion (P = 0.047). Degree of immunoreactivity had no significant correlation with tumor grade, node metastasis and distant metastasis. In terms of prognostic significance, univariate analysis showed that poor differentiation [41 (66.1%) vs 34 (42.5%) P = 0.051], advanced tumor stage (P < 0.001) and weakly altered pRb expression [17 (80.5%) vs 58 (49.6%) P = 0.044] were associated with worse prognosis in these patients. However, multivariate analysis revealed that advanced tumor stage was the only independent poor prognostic factor (P < 0.001). CONCLUSION: The mutation of Rb gene is frequent in gastric carcinoma. The expression of altered pRb inversely correlates with tumor invasion and is not an independent prognostic marker in gastric adenocarcinoma.

Screening and prevention of hepatitis C virus reactivation during chemotherapy

Hepatitis C virus(HCV)reactivation occurs in 23%of HCV-infected cancer patients receiving chemotherapy.Forty-three percent of the patients with reactivation of HCV during chemotherapy develop a hepatitis flare.Most of the cancer patients with HCV reactivation have an unremarkable clinical course following an HCV-related hepatitis flare during chemotherapy.However,26%–57%of the cancer patients developing an acute flare of chronic hepatitis C during chemotherapy require unanticipated discontinuation or dose reduction of chemotherapy,which results in deleterious changes in the cancer treatment plan.Although an optimal strategy for HCV screening in cancer patients receiving chemotherapy has not been established,universal pre-chemotherapy HCV testing for patients with hematological malignancies is recommended by current guidelines.All the currently approved direct-acting antivirals(DAAs)can be used in cancer patients,but the use of DAAs during chemotherapy should avoid drug–drug interactions between chemotherapy and antiviral agents.If there are no contraindications or anticipated drug–drug interactions,DAAs treatment can be administered before,during,or after chemotherapy.In conclusion,HCV reactivation occurs in approximately one-fourth of HCV-infected cancer patients receiving chemotherapy.An HCV-related hepatitis flare during chemotherapy may lead to the discontinuation of potentially life-saving chemotherapy.Currently,universal HCV screening is recommended in hematological malignancy patients before chemotherapy,but there is no evidence-based guideline for other cancer patients.DAAs treatment can cure HCV infection and prevent HCV reactivation during chemotherapy.

Prevalence and risk factors for Candida esophagitis among human immunodeficiency virus-negative individuals

BACKGROUND Candida esophagitis(CE) is among the commonest esophageal infections and is known as an opportunistic fungal infection mostly affecting people living with the human immunodeficiency virus(HIV).However,some medical conditions might predispose HIV-negative individuals to esophageal candidiasis.The epidemiology and associated endoscopic findings of CE among people without HIV have rarely been reported.AIM To investigate the prevalence of CE among HIV-negative persons,and determine risk factors predicting CE.METHODS Between January 2015 and December 2018,all consecutive outpatients who underwent routine esophagogastroduodenoscopy as part of health check-ups at their own expense at the Health Check-up Center of the Kaohsiung Veterans General Hospital,Taiwan,were recruited in this study.Those with positive HIV serology results were excluded.Sociodemographic and clinical characteristics including age,gender,economic status,smoking history,alcohol consumption,tea and coffee consumption,underlying diseases,body fat percentage,body mass index,endoscopic findings,and Helicobacter pylori infection status were carefully reviewed.CE was confirmed by endoscopic biopsy and pathological assessment with hematoxylin and eosin and periodic acidSchiff staining.To evaluate independent factors predicting the development of CE,we conducted a univariate analysis of clinical characteristics.The variables found to be significant via univariate analysis were subsequently included in a multivariable analysis of potential risk factors for CE development.RESULTS A total of 11802 participants were included in this study.Forty-seven(0.4%) were confirmed as having CE by pathological examination.Univariate analysis identified older age,the presence of chronic kidney disease,alcohol consumption,and steroid use(P = 0.023,< 0.001,0.033,and 0.004,respectively) as significantly associated with CE.Multivariable analysis revealed older age [adjusted odds ratio(OR) = 1.027;95%CI:1.001-1.053;P = 0.045],chronic kidney disease(adjusted OR = 13.470;95%CI:4.574-39.673;P < 0.001),alcohol consumption(adjusted OR = 2.103;95%CI:1.151-3.844;P = 0.016),and steroid use(adjusted OR = 24.255;95%CI:5.343-110.115;P < 0.001) as independent risk factors for CE development.The presence of dysphagia was associated with severe CE(P = 0.021).CONCLUSION The prevalence of CE among HIV-negative persons was 0.4% in Taiwan.Independent risk factors for CE were older age,chronic kidney disease,alcohol consumption,and steroid use.