Distal Biliary Stent Migration in Patients with Irretrievable Bile Duct Stones: Long-Term Comparison Between Straight and Double-Pigtail Stents.

BACKGROUND: Prolonged biliary stenting may be considered in high-risk patients with irretrievable bile duct stones (IBDS). Distal stent migration (DSM) is a known complication, although data beyond the recommended interval of temporary stenting (3-6 months) are lacking. We compared the long-term incidence of DSM between straight and double-pigtail stents in patients with IBDS. METHODS: Consecutive patients with IBDS undergoing plastic biliary stenting (1/2009-12/2019) were retrospectively reviewed. DSM was confirmed on follow-up examination when the stent was no longer present at the papillary orifice nor fluoroscopically visible in the bile duct. Kaplan-Meier and Cox regression analyses were used to determine estimates and predictors of DSM. RESULTS: Overall, 618 biliary stenting procedures (410 patients) were included: 289 with a straight stent (group A) and 329 with a double-pigtail (group B). By Kaplan-Meier analysis, the DSM rates were 8.4 and 14.6% at 6 months, 21.4 and 27.7% at 12 months, 27 and 43.5% at 18 months, and 37.2 and 60.4% at 24 months, for groups A and B, respectively (p = 0.004). Double-pigtail stents were at higher risk for DSM (HR = 7.38, p = 0.04), whereas an inverse correlation was noted with age (HR = 0.97, p = 0.0001). Considering only temporary stenting procedures (≤ 6 months; n = 297), the probability of DSM was not significantly different between the two groups (p = 0.07). CONCLUSIONS: In a setting of prolonged stenting for IBDS, the probability of DSM appears to be higher when a double-pigtail stent is used and in younger patients. A relative anti-migratory advantage of double-pigtail over straight stents appears negligible in this study.

Cold snare polypectomy vs. hot snare polypectomy vs. argon plasma coagulation for small (5-9mm) left-sided colorectal polyps: a prospective randomized trial.

OBJECTIVE: To compare recurrence rates among three endoscopic treatment modalities for 5-9 mm left-sided colorectal polyps. METHODS: Consecutive adults referred for elective colonoscopy (1/2015-1/2018) with at least one polyp of eligible size (5-9 mm) located distally to the splenic flexure were randomly assigned (1:1:1) to one of three treatment modalities: (1) cold snare polypectomy (CSP), (2) hot snare polypectomy (HSP) and (3) argon plasma coagulation (APC) ablation (50-60 W, flow: 2 l/min). The polyp site was marked with an endoscopic tattoo, and a follow-up colonoscopy with scar biopsies was performed >6 months after the index procedure. Outcomes were polyp recurrence rate and occurrence of complications. RESULTS: One hundred nineteen patients were enrolled, of whom 112 (62.5% males, mean age 61.1 ± 9.9 years) with 121 polyps (CSP, 39; HSP, 45; APC, 37) returned for follow-up colonoscopy. Mean polyp size was 6.7 ± 0.91 mm, 58% were located in the sigmoid, 33% in the rectum and 8% in the descending colon. The majority of polyps resected by CSP or HSP were neoplastic (tubular adenomas: 25.9%, tubulovillous adenomas: 11.1% and sessile serrate adenomas/polyps: 17.5%). No cases of delayed bleeding or perforation occurred. Scar biopsies at follow-up colonoscopy (performed after a mean interval of 13.4 ± 3.8 months) revealed 7 (5.8%) cases of polyp recurrence, showing no significant difference among the three treatment groups [CSP, 3/39 (7.7%); HSP, 1/45 (2.2%); APC, 2/37 (5.4%); P = 0.51). CONCLUSIONS: CSP, HSP and APC-ablation are effective and well-tolerated treatment modalities for 5-9 mm left-sided colorectal polyps. The present randomized study did not detect any difference in polyp recurrence rate among the three endoscopic techniques.

An update on current and advancing pharmacotherapy options for the treatment of H. pylori infection.

Introduction: Eradication of Helicobacter pylori (H. pylori) becomes more challenging due to increasing antimicrobial resistance. Consequently, the performance of clarithromycin-containing triple therapies is now declining to unacceptable levels and should be abandoned unless a prior susceptibility test precludes clarithromycin resistance.Areas covered: This review summarizes updated evidence concerning new and advancing pharmacotherapy options for H. pylori eradication.Expert opinion: Due to the declining efficacy of legacy triple therapies, most guidelines recommend bismuth quadruple therapy as the best initial empiric treatment. Concomitant, sequential and hybrid therapies are remarkable bismuth-free quadruple options, provided that dual clarithromycin-metronidazole resistance is low. Levofloxacin-, rifabutin-, furazolidone- and sitafloxacin-containing regimens remain useful, particularly as salvage options. To eradicate H. pylori in line with the rules of antibiotic stewardship, susceptibility-guided treatment appears as the ideal approach. However, the feasibility and cost-effectiveness of universal pre-treatment susceptibility testing warrants further evaluation. Molecular testing methods promise convenient characterization of H. pylori antibiotic susceptibility. High-dose dual therapy (proton-pump-inhibitor plus amoxicillin) and vonoprazan, a more potent acid inhibitor that likely enhances the activity of amoxicillin, are promising alternatives that could decrease misuse of antibiotics. Addition of certain probiotics could somewhat increase the performance of H. pylori eradication regimens, while improving tolerability.

Simulated performance of flexible sigmoidoscopy-based screening for advanced neoplasia detection in a Greek population.

BACKGROUND: Flexible sigmoidoscopy (FS) is resource-conserving and may increase adherence to colorectal cancer (CRC) screening compared to total colonoscopy. We investigated the diagnostic performance of FS-based screening for advanced colorectal neoplasia (ACN), including advanced adenomatous neoplasms (AANs), advanced serrated lesions (ASLs) and CRCs. METHODS: Data from 2005 subjects undergoing average-risk screening colonoscopy in a single center in Greece were retrospectively reviewed. Sensitivities of FS-based screening for detecting AANs, ASLs, CRCs or any ACN were simulated on a per-lesion basis, assuming: 1) FS up to the sigmoid-descending junction (FS-1) or splenic flexure (FS-2); 2) colonoscopy referral criteria according to the 4 screening FS trials conducted in UK, Italy, Norway, and USA. RESULTS: Overall, 114 ACNs (93 AANs, 17 ASLs, 4 CRCs) were detected in 102 (5.1%) subjects. The overall sensitivities of FS-1 and FS-2 alone for the detection of any ACN were 41.2% and 54.4%, respectively. Assuming different colonoscopy referral criteria, the estimated sensitivities for any ACN ranged from 48.2-50.9% for FS-1 and 60.5-64% for FS-2. The overall sensitivities were lower for ASLs (FS-1: 35.3-41.2%, FS-2: 41.2-52.9%) compared to those observed for AANs (FS-1: 48.4-51.6%, FS-2: 62.4-66.7%). The difference was particularly pronounced in women, in whom all 4 criteria led equally to a very low sensitivity for ASLs (30%). CONCLUSIONS: Implementation of FS-based screening in Greek subjects would have led to the detection of 48-64% of all ACNs. An alarmingly low detection of ASLs among women may call for gender-specific colonoscopy referral strategies.

Persistence and adherence to nucleos(t)ide analogues in chronic hepatitis B: a multicenter cohort study.

BACKGROUND: Adherence and persistence to long-term therapy with nucleos(t)ides analogues are crucial to the outcome of treatment in chronic hepatitis B. Our aim was to determine the persistence and adherence rates to nucleos(t)ides analogues in chronic hepatitis B patients under maintenance therapy and to identify relative to prediction of adherence factors. METHODS: We retrospectively analyzed electronic prescription data of patients (2011-2016; n = 400) with chronic hepatitis B treated with nucleos(t)ides analogues at 4 tertiary liver centers in Greece. RESULTS: Two hundred ninety-six of 400 patients were under or initiated treatment in 2011-2012 (existing patients), while the remainder initiated or switched medication from January 2013 and onward (new patients). The median adherence rate was 99%, with 89.7% achieving adherence >80% during a mean follow-up of 28 ± 14 months. The overall 12-month persistence rate was 57%, with no difference between patients receiving tenofovir, entecavir or double therapy (57.8%, 52.8% and 68.4%, respectively, P = 0.399). The decline in persistence was more pronounced during the first 3 months of follow-up and in existing patients (P = 0.057). Overall, 80% and 55.1% of nonpersistent patients succeeded adherence to nucleos(t)ides analogues >80% and >90%, respectively. Multivariate analyses showed that existing (vs. new) patients were less likely to have >80% adherence (odds ratio: 0.324, P = 0.44) and persistence (odds ratio: 0.562, P = 0.057) to nucleos(t)ides analogues therapy. CONCLUSION: In this real-world cohort of chronic hepatitis B patients, high adherence to nucleos(t)ides analogues was coupled with suboptimal persistence with prescribing the medication. Our data indicate that persistence and adherence are distinct measures that should be approached separately in educational programs targeting to improve medication-taking behavior in chronic hepatitis B.

Comparison of digital versus fiberoptic cholangioscopy in patients requiring evaluation of bile duct disease or treatment of biliary stones.

BACKGROUND: Recently, the introduction of the novel digital SpyGlass™ DS Direct Visualization system (Boston Scientific Corp., Natick, MA, USA) has signaled the transition into the era of digital single-operator cholangioscopy (D-SOC). We sought to compare the clinical utility between fiberoptic single-operator cholangioscopy (F-SOC) and D-SOC in a tertiary-care referral center in Greece. METHODS: This was a retrospective analysis of a prospective database of single-operator cholangioscopy (SOC) procedures performed over an 8-year period (2009-2017) at a single tertiary-care referral center. The study population consisted of consecutive adults referred for cholangioscopy for a variety of clinical indications, including biliary strictures, difficult biliary stones and migrated or occluded pancreatic or biliary stents. RESULTS: A total of 2763 endoscopic retrograde cholangiopancreatography procedures were performed during the study period. Overall, SOC was performed in 68 (2.46%) procedures (F-SOC=39, D-SOC=29), showing a significant increase in the utilization of cholangioscopy during the D-SOC (29/599; 4.84%) compared with the F-SOC (39/2124; 1.83%) period (P=0.0001). The overall technical success of diagnostic SOC was 69.1% (38/55), being marginally higher for D-SOC (83.3%) than for F-SOC (58.1%), although not reaching statistical significance (P=0.07). CONCLUSIONS: D-SOC was utilized more frequently in our tertiary-care non-academic referral center, demonstrating a favorable safety profile and a trend towards a marginally higher technical success rate for the diagnosis of biliary strictures compared with F-SOC.

Seven-day genotypic resistance-guided triple Helicobacter pylori eradication therapy can be highly effective.

BACKGROUND: The efficacy and applicability of molecular testing to guide the selection of antibiotics in triple Helicobacter pylori (H. pylori) eradication regimens have not been reported. We tested a 7-day, genotypic resistance-guided triple H. pylori eradication therapy in a high-resistance setting. METHODS: Consecutive dyspeptic patients with H. pylori infection were prospectively enrolled. Genotypic resistances to clarithromycin (23SrRNA mutations) and fluoroquinolones (gyrA mutations) were determined from gastric biopsy specimens using a commercially available molecular assay (GenoTypeâ HelicoDR). A tailored genotypic resistance-guided 7-day triple therapy comprised esomeprazole, amoxicillin, and either clarithromycin (wild-type 23SrRNA), levofloxacin (23SrRNA mutated/wild-type gyrA) or rifabutin (both 23SrRNA/gyrA mutated). H. pylori eradication was confirmed by 13C-urea breath test. RESULTS: Of 148 subjects screened, 51 patients were enrolled (male/female: 27/24, mean age: 50.7±11.4 years, treatment-naïve/-experienced: 32/19). The molecular kit was easily implemented, allowing for rapid (within 24 h) and relatively inexpensive determination of H. pylori resistance (clarithromycin: 47.1%, fluoroquinolones: 15.7%, dual clarithromycin/fluoroquinolones: 7.8%). For patients who received clarithromycin-, levofloxacin- and rifabutin-containing triple therapy, the respective eradication rates were 24/27, 20/20, and 2/4 by intention-to-treat (ITT); and 24/24, 19/19 and 2/3 by per-protocol (PP) analysis. Overall eradication rates were 90.2% (95% confidence interval [CI] 77.8-96.3%) by ITT and 97.8% (95%CI 87-99.8%) by PP analysis, showing no significant difference between treatment-naïve and -experienced patients (ITT: 87.5% vs. 94.7%, P=0.64; PP: 96.4% vs. 100%, respectively, P=1.00). CONCLUSIONS: Regardless of prior treatment history, a genotypic resistance-guided 7-day triple therapy, based on a simple molecular assay, achieved a high H. pylori eradication rate.

Hybrid therapy as first-line regimen for Helicobacter pylori eradication in a high clarithromycin resistance area: a prospective open-label trial.

BACKGROUND: Hybrid therapy is a promising first-line regimen for Helicobacter pylori (H. pylori) eradication. We evaluated a hybrid therapy, assessing the impact of antibiotic resistance on eradication outcome. METHODS: This was a prospective study that included 155 treatment-naïve patients diagnosed with H. pylori infection by positive CLO-test, confirmed with histology and/or culture. The hybrid therapy consisted of 40 mg esomeprazole and 1 g amoxicillin for 14 days, with the addition of 500 mg clarithromycin and 500 mg metronidazole for the final 7 days (all b.i.d.). Eradication was defined by negative 13C-urea breath test or histology. RESULTS: The eradication rates were 85.8% (133/155; 95% confidence interval [CI] 79.4-90.5%) by intention-to-treat and 90.2% (129/143; 95%CI 84.1-94.2%) by per-protocol analysis in a setting of high antibiotic resistance (clarithromycin 25.9%, metronidazole 31.1%, dual resistance 8.9%). Adverse events occurred in 29.7% and 1.3% discontinued treatment because of adverse events. Adherence >90% was achieved in 96.6%. The eradication rate in patients with dual clarithromycin/metronidazole resistance (50%) was markedly lower compared to those with single clarithromycin resistance (91.4%), single metronidazole resistance (90.5%) or dual susceptibility (97.8%). Dual resistance was the only factor to correlate with the failure of hybrid therapy (odds ratio 14.4, 95%CI 3.8-54.9, P=0.0003). CONCLUSIONS: Hybrid therapy is an effective and safe first-line regimen in populations with relatively high rates of antibiotic resistance. However, dual clarithromycin/metronidazole resistance may significantly compromise its efficacy.

Cold versus hot endoscopic mucosal resection for nonpedunculated colorectal polyps sized 6-10 mm: a randomized trial.

BACKGROUND AND STUDY AIMS: Cold snare polypectomy is an established method for the resection of small colorectal polyps; however, significant incomplete resection rates still leave room for improvement. We aimed to assess the efficacy of cold snare endoscopic mucosal resection (CS-EMR), compared with hot snare endoscopic mucosal resection (HS-EMR), for nonpedunculated polyps sized 6 - 10 mm. PATIENTS AND METHODS: This study was a dual-center, randomized, noninferiority trial. Consecutive adult patients with at least one nonpedunculated polyp sized 6 - 10 mm were enrolled. Eligible polyps were randomized (1:1) to be treated with either CS-EMR or HS-EMR. Both methods involved submucosal injection of a methylene blue-tinted normal saline solution. The primary noninferiority end point was histological eradication evaluated by postpolypectomy biopsies (noninferiority margin - 10 %). Secondary outcomes included occurrence of intraprocedural bleeding, clinically significant postprocedural bleeding, and perforation. RESULTS: Among 689 patients screened, 155 patients with 164 eligible polyps were included (CS-EMR n = 83, HS-EMR n = 81). The overall rate of histological complete resection was 92.8 % in the CS-EMR group and 96.3 % in the HS-EMR group (difference 3.5 %; 95 % confidence interval [CI] - 4.15 to 11.56), showing noninferiority of CS-EMR compared with HS-EMR. CS-EMR was shown to be noninferior both for polyps measuring 6 - 7 mm (CS-EMR 93.3 %; HS-EMR 100 %; 95 %CI - 7.95 to 21.3) and those of 8 - 10 mm (92.5 % vs. 94.7 %, respectively; 95 %CI - 7.91 to 13.16). Rates of intraprocedural bleeding were similar between the two groups (CS-EMR 3.6 %, HS-EMR 1.2 %; P  = 0.30). No clinically significant postprocedural bleeding or perforation occurred in either group. CONCLUSIONS: CS-EMR appears to be a valuable modification of the standard cold snare technique, obviating the need to use diathermy for nonpedunculated colorectal polyps sized 6 - 10 mm.

Long-term recurrence of bile duct stones after endoscopic papillary large balloon dilation with sphincterotomy: 4-year extended follow-up of a randomized trial.

BACKGROUND: Endoscopic papillary large balloon dilation with biliary sphincterotomy (EPLBD + EBS) is safe and effective in patients with large common bile duct (CBD) stones. However, data on long-term outcomes after EPLBD + EBS remain limited. We sought to prospectively evaluate the long-term recurrence of CBD stones after EPLBD + EBS and to identify the associated factors. METHODS: We conducted an extended follow-up of a previous randomized trial (2009-2011) comparing the outcomes of 30- versus 60-s large balloon dilation. A total of 106 trial participants undergoing successful CBD stone clearance by EPLBD + EBS were prospectively followed up for up to 4 years (range 19-48 months). Various risk factors were analysed to assess predictors of long-term recurrence of stones. RESULTS: Recurrent CBD stones appeared in 8/106 (7.5 %) patients during a mean follow-up of 30.5 ± 5.5 months. The mean diameter of CBD was significantly higher in the recurrence versus non-recurrence group (2.0 ± 4.9 vs 1.6 ± 0.9 cm, p = 0.008). Multivariate analysis revealed that CBD diameter was the only predictor significantly associated with the long-term recurrence of stones (odds ratio 1.2, p = 0.01). CONCLUSIONS: EPLBD + EBS is associated with a low rate of long-term CBD stone recurrence. However, the risk is significantly higher in patients with a more dilated CBD.

A delayed onset of bowel activity after the start of conventional polyethylene glycol predicts inadequate colon cleansing before colonoscopy: A prospective observational study.

BACKGROUND: Evaluation of factors correlating with the quality of bowel preparation (QBP) is critical to ensure high-quality colonoscopy. OBJECTIVES: We sought to determine whether the time interval between the start of conventional polyethylene glycol (PEG) ingestion and the onset of bowel activity is predictive of QBP. METHODS: Consecutive adult outpatients attending colonoscopy were prospectively assessed. Data including demographics, medical history, time of starting/completion of PEG and time when bowel activity started were recorded. The QBP was assessed according to the Ottawa bowel preparation score (OBPS); inadequate QBP was OBPS ≥7. RESULTS: A total of 171 patients (92 males, mean age: 60.5 years) complying with preparation instructions were included. The median OBPS was 5 (range: 1-13) and 57 (33.3%) had inadequate QBP. The median interval between the initiation of PEG and the onset of bowel activity was 60 min (range: 9-300 min). Patients (n = 52, 30.4%) with a delayed (>90 min) onset of bowel activity had poorer QBP (p = 0.0001). In multivariate analysis, male gender (OR: 2.38, p = 0.03), the interval between the end of preparation and the start of colonoscopy (OR: 1.94, p = 0.02) and time to onset of bowel activity >90 min (OR: 3.38, p = 0.004) were predictive of inadequate QBP. CONCLUSION: The time interval between the initiation of PEG ingestion and the onset of bowel activity is predictive of the QBP. Our data support "on demand" intensification of bowel preparation in patients with a delayed onset of purgative response to PEG.

Helicobacter pylori and colorectal neoplasia: Is there a causal link?

Ever since Helicobacter pylori (H. pylori) was recognized as an infectious cause of gastric cancer, there has been increasing interest in examining its potential role in colorectal carcinogenesis. Data from case-control and cross-sectional studies, mostly relying on hospital-based samples, and several meta-analyses have shown a positive statistical relationship between H. pylori infection and colorectal neoplasia. However, the possibility exists that the results have been influenced by bias, including the improper selection of patients and disparities with respect to potential confounders. While the evidence falls short of a definitive causal link, it appears that infection with H. pylori/H. pylori-related gastritis is associated with an increased, although modest, risk of colorectal adenoma and cancer. The pathogenic mechanisms responsible for this association remain uncertain. H. pylori has been detected in colorectal malignant tissues; however, the possibility that H. pylori is a direct activator of colonic carcinogenesis remains purely hypothetical. On the other hand, experimental data have indicated a series of potential oncogenic interactions between these bacteria and colorectal mucosa, including induction and perpetuation of inflammatory responses, alteration of gut microflora and release of toxins and/or hormonal mediators, such as gastrin, which may contribute to tumor formation.

Treatment of Helicobacter Pylori infection: optimization strategies in a high resistance era.

INTRODUCTION: Treatment of Helicobacter pylori (H. pylori) infection is paramount for the management of prevalent gastrointestinal disorders and in the prevention of gastric cancer. Due to increasing antimicrobial resistance, performance of standard triple therapies has now declined to unacceptably low levels. AREAS COVERED: In this article: i) we critically revise optimization tools aiming to improve the outcome of standard treatments; ii) we provide updated evidence on the efficacy and rationale for the use of several non-bismuth quadruple regimens in clinical practice, recommended as preferred empirical therapies in areas of high clarithromycin resistance. EXPERT OPINION: Prolonged (14-day) treatment duration may boost the efficacy of standard triple therapy by approximately 5%. Use of a high-dose PPI and/or new-generation PPIs, rabeprazole and esomeprazole, might improve eradication rates, particularly in regions where the CYP2C19 rapid metabolizer phenotype is prevalent. Adjunctive probiotics may be considered to improve treatment tolerability, though more data are required to better define their role in H. pylori eradication. Among non-bismuth quadruple regimens, both concomitant and sequential therapies are appropriate options for high-resistance settings; however, concomitant therapy appears to be less impaired by dual clarithromycin/metronidazole resistance. Hybrid therapy is a promising new alternative which seems not to be inferior to concomitant therapy.

Current status and emerging challenges in the treatment of hepatitis C virus genotypes 4 to 6.

Hepatitis C virus (HCV) genotypes 4, 5 and 6 are mainly present in Africa, the Middle East and Asia and they have been less extensively studied with respect to epidemiology, natural disease history and therapeutic endpoints. Response rates to a 48-wk combined peginterferon/ribavirin treatment range to 40%-69% for HCV 4, 55%-60% for HCV 5 and 60%-90% for HCV 6. Response-guided schedules are recommended to optimize the outcomes of peginterferon/ribavirin treatment in HCV 4 and, in form of preliminary data, for HCV 6, but no data are yet available to support such an individualization of therapy for HCV 5. Recently, the direct-acting antivirals (DAAs) with pan-genotypic activities simeprevir, sofosbuvir and daclatasvir have been recommended in triple regimens with peginterferon/ribavirin for the treatment of HCV genotypes 4 to 6 infections. In the future, DAA-based interferon-free therapies are awaited to drastically improve treatment outcomes in HCV. However, efforts to improve treatment outcomes with peginterferon/ribavirin should continue, as the HCV 4-6 infected population is mainly based in resource-limited settings with restricted access to the costly DAAs.

Treatment of Helicobacter pylori infection: Past, present and future.

Helicobacter pylori (H. pylori) is a major human pathogen associated with significant morbidity and mortality. However, after decades of efforts, treatment of H. pylori remains a challenge for physicians, as there is no universally effective regimen. Due to the rising prevalence of antimicrobial resistance, mainly to clarithromycin, efficacy of standard triple therapies has declined to unacceptably low levels in most parts of the world. Novel regimens, specifically experimented to improve the therapeutic outcome against antibiotic-resistant H. pylori strains, are now recommended as first-line empirical treatment options providing high efficacy (reportedly > 90% in intention to treat analysis) even in high clarithromycin resistance settings. These include the bismuth quadruple, concomitant, sequential and hybrid therapies. Due to the rapid development of quinolone resistance, levofloxacin-based regimens should be reserved as second-line/rescue options. Adjunct use of probiotics has been proposed in order to boost eradication rates and decrease occurrence of treatment-related side effects. Molecular testing methods are currently available for the characterization of H. pylori therapeutic susceptibility, including genotypic detection of macrolide resistance and evaluation of the cytochrome P450 2C19 status known to affect the metabolism of proton pump inhibitors. In the future, use of these techniques may allow for culture-free, non-invasive tailoring of therapy for H. pylori infection.