How Does Aging Affect Presentation and Management of Biliary Stones?

Common bile duct (CBD) stones are common in elderly adults, but the effect of aging on the presentation of CBD stones remains to be evaluated. Recent studies have demonstrated that the clinical presentation of CBD stones may vary with age. Younger adults may present with classical biliary colic symptoms, whereas elderly adults may have no unapparent clinical features. Younger adults with CBD stones were significantly more likely to have abnormal liver function tests than those without. The sensitivity and accuracy of transabdominal ultrasound scans in screening for CBD stones increases with age. Antibiotic agents should be promptly administered to individuals with CBD stones complicated by cholangitis, but the effects of pharmacotherapy on renal function should be considered in elderly adults. Endoscopic retrograde cholangiopancreatography (ERCP) is considered to be first-line treatment for CBD stones, and endoscopic biliary sphincterotomy (EST) or endoscopic papillary balloon dilation (EPBD) along with ERCP is an adequate biliary drainage method in individuals with CBD stones. EPBD has a lower bleeding risk but higher post-ERCP risk of pancreatitis than EST. Longer-duration (>1 minute) EPBD may be preferred over EST because it is associated with a comparable risk of pancreatitis but a lower rate of overall complications, although recurrent cholangitis or unfavorable outcomes will increase during CBD dilation or in the presence of residual CBD stones.

Levofloxacin Sequential Therapy vs Levofloxacin Triple Therapy in the Second-Line Treatment of Helicobacter pylori: A Randomized Trial.

OBJECTIVES: The efficacy of levofloxacin triple therapy has fallen below 80% in the second-line treatment of Helicobacter pylori (H. pylori). We aimed to assess whether the levofloxacin sequential therapy is more effective than levofloxacin triple therapy in the second-line treatment. METHODS: This open-label, randomized, multicenter trial was conducted between 2012 and 2015. H. pylori-infected subjects who failed from clarithromycin-based regimens (N=600) were randomized (1:1) to receive levofloxacin sequential therapy (LS: lansoprazole and amoxicillin for the first 5 days, followed by lansoprazole, levofloxacin, and metronidazole for another 5 days) or levofloxacin triple therapy (LT: lansoprazole, amoxicillin, and levofloxacin for 10 days). Successful eradication was defined as negative (13)C-urea breath test at least 6 weeks after treatment. Our primary outcome was the eradication rate by intention-to-treat (ITT) and per-protocol (PP) analyses. Antibiotic resistance was determined by agar dilution test. RESULTS: The prevalence of clarithromycin, levofloxacin, and metronidazole resistance was 60, 17.6, and 36.9%, respectively. The eradication rates of LS and LT were 84.3% (253/300) and 75.3% (226/300), respectively, in the ITT analysis (P=0.006) and 86.3% (253/293) and 78.8% (223/283), respectively, in the PP analysis (P=0.021). The efficacies of both LS and LT were affected by levofloxacin resistance. The secondary resistance of levofloxacin was 66.7 and 73.9% after LS and LT, respectively. The efficacies of LS and LT were not affected by the CYP2C19 polymorphism. CONCLUSIONS: Levofloxacin sequential therapy was more effective than levofloxacin triple therapy, and it is recommended in the second-line treatment for H. pylori ( TRIAL REGISTRATION NUMBER: NCT01537055).

Sequential therapy for 10†days versus triple therapy for 14†days in the eradication of Helicobacter pylori in the community and hospital populations: a randomised trial.

OBJECTIVE: Significant heterogeneity was observed in previous trials that assessed the efficacies of sequential therapy for 10 days (S10) versus triple therapy for 14 days (T14) in the first-line treatment of Helicobacter pylori. We aimed to compare the efficacy of S10 and T14 and assess the factors affecting their efficacies. DESIGN: We conducted this open-label randomised multicentre trial in eight hospitals and one community in Taiwan. 1300 adult subjects with H pylori infection naïve to treatment were randomised (1:1) to receive S10 (lansoprazole and amoxicillin for the first 5 days, followed by lansoprazole, clarithromycin and metronidazole for another 5 days) or T14 (lansoprazole, amoxicillin and clarithromycin for 14 days). All drugs were given twice daily. Successful eradication was defined as negative 13C-urea breath test at least 6 weeks after treatment. Our primary outcome was the eradication rate by intention-to-treat (ITT) and per-protocol (PP) analyses. Antibiotic resistance was determined by agar dilution test. RESULTS: The eradication rates of S10 and T14 were 87.2% (567/650, 95% CI 84.4% to 89.6%) and 85.7% (557/650, 95% CI 82.8% to 88.2%) in the ITT analysis, respectively, and were 91.6% (556/607, 95% CI 89.1% to 93.4%) and 91.0% (548/602, 95% CI 88.5% to 93.1%) in the PP analysis, respectively. There were no differences in compliance or adverse effects. The eradication rates in strains susceptible and resistant to clarithromycin were 90.7% and 62.2%, respectively, for S10, and were 91.5% and 44.4%, respectively, for T14. The efficacy of T14, but not S10, was affected by CYP2C19 polymorphism. CONCLUSIONS: S10 was not superior to T14 in areas with low clarithromycin resistance. TRIAL REGISTRATION NUMBER: NCT01607918.

The Primary Resistance of Helicobacter pylori in Taiwan after the National Policy to Restrict Antibiotic Consumption and Its Relation to Virulence Factors-A Nationwide Study.

OBJECTIVE: The Taiwan Government issued a policy to restrict antimicrobial usage since 2001. We aimed to assess the changes in the antibiotic consumption and the primary resistance of H. pylori after this policy and the impact of virulence factors on resistance. METHODS: The defined daily dose (DDD) of antibiotics was analyzed using the Taiwan National Health Insurance (NHI) research database. H. pylori strains isolated from treatment naïve (N=1395) and failure from prior eradication therapies (N=360) from 9 hospitals between 2000 and 2012 were used for analysis. The minimum inhibitory concentration was determined by agar dilution test. Genotyping for CagA and VacA was determined by PCR method. RESULTS: The DDD per 1000 persons per day of macrolides reduced from 1.12 in 1997 to 0.19 in 2008, whereas that of fluoroquinolones increased from 0.12 in 1997 to 0.35 in 2008. The primary resistance of amoxicillin, clarithromycin, metronidazole, and tetracycline remained as low as 2.2%, 7.9%, 23.7%, and 1.9% respectively. However, the primary levofloxacin resistance rose from 4.9% in 2000-2007 to 8.3% in 2008-2010 and 13.4% in 2011-2012 (p=0.001). The primary resistance of metronidazole was higher in females than males (33.1% vs. 18.8%, p<0.001), which was probably attributed to the higher consumption of nitroimidazole. Neither CagA nor VacA was associated with antibiotic resistance. CONCLUSIONS: The low primary clarithromycin and metronidazole resistance of H. pylori in Taiwan might be attributed to the reduced consumption of macrolides and nitroimidazole after the national policy to restrict antimicrobial usage. Yet, further strategies are needed to restrict the consumption of fluoroquinolones in the face of rising levofloxacin resistance.

Distinct aetiopathogenesis in subgroups of functional dyspepsia according to the Rome III criteria.

BACKGROUND AND OBJECTIVE: Whether there is distinct pathogenesis in subgroups of functional dyspepsia (FD), the postprandial distress syndrome (PDS) and epigastric pain syndrome (EPS) remains controversial. We aimed to identify the risk factors of FD and its subgroups in the Chinese population. METHODS: Patients with dyspepsia and healthy subjects who underwent gastric cancer screening were enrolled in this multicentre study from 2010 to 2012. All patients were evaluated by questionnaire, oesophagoduodenoscopy, histological examination and Helicobacter pylori tests. Subgroups of FD were classified according to the Rome III criteria. Psychiatric stress was assessed by the short form Brief Symptom Rating Scale. CagA and VacA genotypes were determined by PCR. RESULTS: Of 2378 patients screened for eligibility, 771 and 491 fulfilled the diagnostic criteria of uninvestigated dyspepsia and FD, respectively. 298 (60.7%) and 353 (71.9%) individuals were diagnosed with EPS and PDS, respectively, whereas 169 (34.4%) had the overlap syndrome. As compared with 1031 healthy controls, PDS and EPS shared some common risk factors, including younger age (OR 0.95; 99.5% CI 0.93 to 0.98), non-steroidal anti-inflammatory drugs (OR 6.60; 99.5% CI 3.13 to 13.90), anxiety (OR 3.41; 99.5% CI 2.01 to 5.77) and concomitant IBS (OR 6.89; 99.5% CI 3.41 to 13.94). By contrast, H. pylori (OR 1.86; 99.5% CI 1.01 to 3.45), unmarried status (OR 4.22; 99.5% CI 2.02 to 8.81), sleep disturbance (OR 2.56; 99.5% CI 1.29 to 5.07) and depression (OR 2.34; 99.5% CI 1.04 to 5.36) were associated with PDS. Moderate to severe antral atrophy and CagA positive strains were also more prevalent in PDS. CONCLUSIONS: Different risk factors exist among FD subgroups based on the Rome III criteria, indicating distinct aetiopathogenesis of the subdivisions that may necessitate different therapeutic strategies.

Peginterferon alfa-2b in the treatment of Chinese patients with HBeAg-positive chronic hepatitis B: a randomized trial.

BACKGROUND: In mainland China, peginterferon (PEG-IFN) alfa-2b 1.0µg/kg/wk for 24 weeks is the approved treatment for HBeAg-positive chronic hepatitis B. OBJECTIVE: This multicenter, randomized trial evaluated the safety and efficacy of regimens utilizing increased dose or treatment duration in treatment-naive Chinese patients with chronic hepatitis B. STUDY DESIGN: 670 HBeAg-positive patients from China, Malaysia, Taiwan area, Singapore, and Thailand were enrolled. Patients received PEG-IFN alfa-2b 1.0µg/kg/wk (arm A) or 1.5µg/kg/wk (arm B) for 24 weeks, or 1.5µg/kg/wk for 48 weeks (arm C). The primary end point was loss of HBeAg 24 weeks after end of treatment. RESULTS: At the end of follow-up, HBeAg loss was significantly greater in arm C compared with arm A (31.3% vs. 17.3%; P=0.001) and arm B (31.3% vs. 18.1%; P=0.001). No significant difference in the rate of HBeAg loss was observed between arms A and B. The proportions of patients with HBe seroconversion, HBV DNA levels <20,000IU/mL, and ALT normalization at the end of follow-up were significantly higher in arm C compared with arm A and arm B. In arms A, B, and C, rates of early treatment discontinuation were 6.3%, 4.9%, and 8.9%; of discontinuation due to an AE, 2%, 3%, and 3%; and of AEs requiring dose modification, 3%, 6%, and 10%, respectively. CONCLUSIONS: In Chinese patients with HBeAg-positive chronic hepatitis B, PEG-IFN alfa-2b 1.5µg/kg/wk for 48 weeks is more efficacious compared with 1.0 and 1.5µg/kg/wk for 24 weeks.

Clinical presentations of patients from different age cohorts with biliary tract stone diseases.

BACKGROUND AND AIM: The role of clinical symptoms, transabdominal ultrasound scan (USS), and liver function tests (LFTs) in evaluating common bile duct (CBD) stones in patients suspected to have pancreatobiliary disease has been studied. However, it is unclear whether these predictive models are useful in different age cohorts. The aim of this study is to investigate the clinical presentations from different age cohorts with and without CBD stones. METHODS: Four hundred and forty-three patients with pancreatobiliary diseases were divided into cohorts according to decades as follows: young (Y, 18-64 years old, n = 143), young-old (YO, 65-74 years old, n = 168), old-old (OO, 75-84 years old, n = 97), and very old (VO, ≥ 85 years old, n = 35). The clinical symptoms, LFTs, and USS findings were demonstrated and compared among patients. RESULTS: Y- and YO-group patients were more likely to develop symptoms such as biliary colic in the presence of CBD stones. The proportion of abnormal serum aspartate aminotransferase and alanine aminotransferase were significantly greater in Y-, YO-, and OO-group patients with than in those without CBD stones. Sensitivity of USS for CBD stones in Y: 0.15; YO: 0.45; OO: 0.57; and VO: 0.68. Accuracy of USS for detected CBD stone in Y: 48%; YO: 62.5%; OO: 70.1%; and VO: 71.4%. CONCLUSION: Combined evaluation of clinical symptoms, biochemical and USS findings may help predict the presence of CBD stones. In Y, YO, and OO patients with CBD stones, the incidences of abnormal LFTs were higher. The sensitivity and accuracy of USS in detecting CBD stones were increased according to age.

Efficacy of genotypic resistance-guided sequential therapy in the third-line treatment of refractory Helicobacter pylori infection: a multicentre clinical trial.

OBJECTIVES: The efficacy of sequential therapy and the applicability of genotypic resistance to guide the selection of antibiotics in the third-line treatment of Helicobacter pylori have not been reported. We aimed to assess the efficacy of genotypic resistance-guided sequential therapy in third-line treatment. METHODS: Genotypic and phenotypic resistances were determined in patients who failed at least two eradication therapies by PCR with direct sequencing and agar dilution test, respectively. The patients were retreated with sequential therapy containing esomeprazole and amoxicillin for the first 7 days, followed by esomeprazole and metronidazole plus clarithromycin, levofloxacin or tetracycline for another 7 days (all twice daily), according to genotypic resistance determined using gastric biopsy specimens. Eradication status was determined by the (13)C-urea breath test. Trial registered at clinicaltrials.gov (identifier: NCT01032655). RESULTS: The overall eradication rate was 80.7% (109/135, 95% CI 73.3%-86.5%) in the intention-to-treat analysis. The presence of amoxicillin resistance (OR 6.83, 95% CI 1.62-28.86, P = 0.009) and prior sequential therapy (OR 4.77, 95% CI 1.315-17.3, P = 0.017), but not tetracycline resistance (tetracycline group), were associated with treatment failure. The eradication rates in patients who received clarithromycin-, levofloxacin- and tetracycline-based sequential therapies were 78.9% (15/19), 92.2% (47/51) and 71.4% (25/35) in strains susceptible to clarithromycin, levofloxacin and tetracycline, respectively. CONCLUSIONS: A simple molecular method guiding sequential therapy can achieve a high eradication rate in the third-line treatment of refractory H. pylori infection.

Sequential versus triple therapy for the first-line treatment of Helicobacter pylori: a multicentre, open-label, randomised trial.

BACKGROUND: Whether sequential treatment can replace triple therapy as the standard treatment for Helicobacter pylori infection is unknown. We compared the efficacy of sequential treatment for 10 days and 14 days with triple therapy for 14 days in first-line treatment. METHODS: For this multicentre, open-label, randomised trial, we recruited patients (≥20 years of age) with H pylori infection from six centres in Taiwan. Using a computer-generated randomisation sequence, we randomly allocated patients (1:1:1; block sizes of six) to either sequential treatment (lansoprazole 30 mg and amoxicillin 1 g for the first 7 days, followed by lansoprazole 30 mg, clarithromycin 500 mg, and metronidazole 500 mg for another 7 days; with all drugs given twice daily) for either 10 days (S-10) or 14 days (S-14), of 14 days of triple therapy (T-14; lansoprazole 30 mg, amoxicillin 1 g, and clarithromycin 500 mg for 14 days; with all drugs given twice daily). Investigators were masked to treatment allocation. Our primary outcome was the eradication rate in first-line treatment by intention-to-treat (ITT) and per-protocol (PP) analyses. This trial is registered with ClinicalTrials.gov, number NCT01042184. FINDINGS: Between Dec 28, 2009, and Sept 24, 2011, we enrolled 900 patients: 300 to each group. The eradication rate was 90·7% (95% CI 87·4-94·0; 272 of 300 patients) in the S-14 group, 87·0% (83·2-90·8; 261 of 300 patients) in the S-10 group, and 82·3% (78·0-86·6; 247 of 300 patients) in the T-14 group. Treatment efficacy was better in the S-14 group than it was in the T-14 group in both the ITT analysis (number needed to treat of 12·0 [95% CI 7·2-34·5]; p=0·003) and PP analyses (13·7 [8·3-40], p=0·003). We recorded no significant difference in the occurrence of adverse effects or in compliance between the three groups. INTERPRETATION: Our findings lend support to the use of sequential treatment as the standard first-line treatment for H pylori infection. FUNDING: National Taiwan University Hospital and National Science Council.

Recurrent cholangitis after endoscopic lithotripsy of common bile duct stones with gallstones in situ: predictive factors with and without subsequent cholecystectomy.

BACKGROUND: Common bile duct stones are a frequent complication of gallstones. Endoscopic retrograde cholangiopancreatography and sphincterotomy are often performed to evaluate the etiology of obstructive jaundice and for concomitant therapeutic removal of common bile duct stones. We aimed to evaluate the recurrence rate of cholangitis or cholecystitis after endoscopic lithotripsy with gallstones in situ and to identify associated predictive factors. PATIENTS AND METHODS: We retrospectively reviewed 183 patients who had received endoscopic lithotripsy between July 2007 and June 2010. We divided patients into two groups: One group who had received subsequent cholecystectomy (n=66) and one observational group (n=117). Patients with previous cholecystectomy or without gallstones were excluded. All included patients were followed up at our outpatient department. Our end point was the presence of symptoms of recurrent cholangitis or cholecystitis. RESULTS: Subjects included 86 males and 97 females with a mean age of 62.5±16.3 years (range, 43-81 years). Cholangitis or cholecystitis recurred in 6 patients in the cholecystectomy group and 30 patients in the observational group. Findings revealed a lower recurrence rate and longer recurrence-free period in patients who received subsequent cholecystectomy. The recurrence rate of the observational group was significantly higher than that of the cholecystectomy group (25.6% versus 9.1%, P=.007). Univariate and multivariate Cox regression analyses revealed that common bile duct dilatation was an independent predictive factor for recurrence. CONCLUSIONS: Cholecystectomy is recommended after endoscopic lithotripsy. Common bile duct dilatation is associated with the rate of recurrent cholangitis or cholecystitis.

Pancreatic head well-differentiated endocrine tumor.

The authors report a case of a small pancreatic head well-differentiated endocrine tumor. A 44-year-old woman was revealed to have a large cystic tumor in the pancreatic head area. Resection revealed a well-differentiated endocrine tumor 7 mm in diameter confined to the pancreatic head and obstructing the proximal portion of the pancreatic duct, resulting in cystic dilatation of the duct, mimicking a cystic tumor of the pancreatic head.

Unusual presentation of desmoid tumor in the small intestine: a case report.

Desmoid tumor originating from the small intestine is extremely rare. We report a 50-year-old man who presented with the sudden onset of severe abdominal pain. Computerized tomography (CT) demonstrated a huge homogeneous tumor in the lower abdomen that appeared to be in continuity with the distal ileum. The mass adherent to the ileum was resected and proved to be a desmoid tumor. The patient has remained recurrence free on follow-up.

Perforated peptic ulcer in southeastern Taiwan.

BACKGROUND: No studies focus on the population with perforated peptic ulcer in southeastern Taiwan. The present study aimed to assess the differences between the different races and the risk factors related to mortality and morbidity in postoperative patients in southeastern Taiwan. METHODS: The medical records of 237 patients were reviewed retrospectively. The following factors were analyzed: patient profiles, coexisting illnesses, diagnostic method, fever, preoperative shock, clinical data at emergency room, delay operation, site of perforation, operative method, positive ascites culture, species of microbes in ascites culture, postoperative complications, death and the length of hospital stay. RESULTS: Aborigines were significantly different from non-aborigines in the ratio of female cases and in the habits of alcohol drinking and betel nut chewing. There were also four significantly different variables between them: fever, hemoglobin value, site of perforation and operative method. Total postoperative complication rate was 41.3% and 39 patients (16.6%) died. In multivariate analysis, age > or = 65 years, lipase > upper normal limit and preoperative shock were independent predictors of mortality. Significant risk factors associated with morbidity were NSAIDs use, creatinine > 1.5 mg/dL and preoperative shock. CONCLUSION: Aborigines were different from non-aborigines in several categories. In southeastern Taiwan, NSAIDs use, creatinine > 1.5 mg/dL and preoperative shock were independent risk factors of morbidity, and age > or = 65 years, lipase > upper normal limit and preoperative shock were independent risk factors of mortality in postoperative perforated peptic ulcer. Lipase > upper normal limit is needed for further research on the influence on mortality.

Acquired hyperplastic gastric polyps after treatment of ulcer.

BACKGROUND/PURPOSE: Healing of gastric ulcers requires repair by epithelial migration and proliferation. We have found a small proportion of patients with acquired hyperplastic polyps at the healed ulcer site. The aim of this study was to identify clinical characteristics that might be associated with the development of hyper-plastic polyps at the site of healed gastric ulcers. METHODS: This was a retrospective review of 86 patients with gastric ulcers from April 2006 to September 2008. After initial endoscopy, the patients were all treated with proton pomp inhibitors, after which a second endoscopy was performed. Demographic data, polyp characteristics (endoscopic and histological), Helicobacter pylori status, and duration of treatment were analyzed. RESULTS: A total of 24 hyperplastic gastric polyps were found in 18 patients; all at the site of the healed ulcer (20 in the antrum and 4 in the corpus). The mean size of the ulcers prior to treatment was 14.5 +/- 9.1 mm. Hyperplastic gastric polyps were more likely to occur at the site of ulcers larger than 10 mm (odds ratio = 9.57, 95% confidence interval =2.50-36.65). Age, sex, H. pylori status, ulcer location and duration of treatment did not differ significantly between patients with and without polyps. CONCLUSION: Hyperplastic polyps that develop after healing of gastric ulcers are likely to be extensive mucosal injury. A gastric ulcer larger than 10 mm is associated with a significantly increased risk of hyperplastic polyps.

Clinical images. Delayed duodenal intramural hematoma with obstruction.

An intramural duodenal hematoma with duodenal obstruction is usually a complication of blunt abdominal trauma, endoscopic biopsy, or peptic ulcer disease. Possible management strategies include conservative treatment, surgical evacuation, and percutaneous or endoscopic drainage. We report on a 40-year-old man with a remote history of trauma who presented with vomiting for 3 days. At surgery, he was found to have an intramural duodenal hematoma causing obstruction.

Duodenal polypoid lipoma with bleeding.

Duodenal lipomas are rare; most are asymptomatic and are found incidentally via endoscopy or surgery. We report a case of duodenal polypoid lipoma with active bleeding. Although endoscopic treatment was scheduled initially, surgical intervention ultimately was indicated.

Findings and risk factors of early mortality of endoscopic retrograde cholangiopancreatography in different cohorts of elderly patients.

OBJECTIVES: To analyze experience of endoscopic retrograde cholangiopancreatography (ERCP) in patients with of different age cohorts and discuss the risk factors of early mortality after ERCP. DESIGN: Retrospective study. SETTING: Tertiary care medical center. PARTICIPANTS: Two hundred sixty-four patients with pancreatobiliary diseases divided into cohorts according to decades as young-old (YO, 65-74, n=143), old-old (OO, 75-84, n=88), and very-old (VO, >or=85, n=33). MEASUREMENTS: The indications, results, and complications of ERCP in these three groups were demonstrated and compared. RESULTS: Three hundred three ERCP procedures were performed. The leading indication for ERCP was common bile duct (CBD) obstruction or dilation. Diabetes mellitus was significantly more prevalent in the YO group (39.2%) than in the other two groups (OO, 15.9%; VO, 24.2%; P=.001). The most common finding of ERCP was CBD dilatation. There was no difference in incidence of malignant diseases between the three groups. Acute pancreatitis was the most frequently identified post-ERCP complication. There was no significant difference in early mortality between the three cohorts. Patients with malignancy had higher early mortality than those with benign disease (71.4% vs 11.2%; P=.001). CONCLUSION: The findings and incidences of complication of ERCP in different elderly cohorts were similar. Underlying malignancy seemed to bear some relation to early mortality after the ERCP procedure.