Clinical trial: seven-day vonoprazan- versus 14-day proton pump inhibitor-based triple therapy for first-line Helicobacter pylori eradication.

BACKGROUND: One-week triple therapy with vonoprazan is endorsed by Japanese guidelines as an alternative to proton pump inhibitor (PPI)-based triple therapy for first-line Helicobacter pylori eradication. This contrasts with Western guidelines recommending 2-week PPI-based triple therapy. AIM: To verify the non-inferiority of 1-week vonoprazan-based triple therapy versus 2-week PPI-based triple therapy as first-line H. pylori eradication in a multiracial Asian cohort. METHODS: Randomised controlled trial of treatment-naïve patients with H. pylori infection assigned 1:1 to either 7 days amoxicillin 1 g + clarithromycin 500 mg + vonoprazan 20 mg twice per day or 14 days amoxicillin 1 g + clarithromycin 500 mg + omeprazole OR esomeprazole OR rabeprazole 20 mg twice/day. Subjects were randomly assigned to each PPI 1:1:1 Demographics, H. pylori resistance, CYP 2C19 genotype, eradication success and safety profiles were compared between groups. RESULTS: Between June 2019 and June 2021, 252 of 1097 subjects screened were randomised. 244 (age [SD] 51.7 [14.6]) received vonoprazan- (n = 119) or PPI-based (n = 125) triple therapy. Eradication rates by intention-to-treat analysis were 87.4% (vonoprazan-based triple therapy) versus 88.0% (PPI-based triple therapy. By per protocol analysis: 96.3% (vonoprazan-based triple therapy) versus 94.0% (PPI-based triple therapy). Clarithromycin resistance predicted treatment failure on multivariate analysis: RR 11.4; 95% CI [1.4-96.3], p = 0.025. No significant differences in CYP 2C19 genotypes or adverse events occurred between groups. CONCLUSION: One-week vonoprazan-based triple therapy achieved comparable efficacy to 2-week PPI-based triple therapy and was well tolerated.

A novel NSDHL variant in CHILD syndrome with gastrointestinal manifestations and localized skin involvement.

BACKGROUND: CHILD syndrome is an X-linked dominant disorder associated with pathogenic mutations in the NSDHL gene. The condition is predominantly found in females as it is lethal in males. Most cases present at birth with extensive unilateral ichthyosiform erythroderma involving the trunk and limbs. Milder and less extensive presentations have been reported, leading to misdiagnosis especially during early childhood. METHODS AND RESULTS: We report an adult female of Malay ancestry who presented with minimal skin and limb involvement. She was only diagnosed in adulthood when she presented with gastrointestinal symptoms and worsening of skin manifestations. The clinical diagnosis was suspected after a combination of clinical, pathological and immunohistochemistry correlation, and molecularly confirmed with the discovery of a frameshift variant in NSDHL. The novel variant was inherited from her mother who had some linear hypopigmented patches over the medial aspects of both her arms and right forearm. CONCLUSION: We uncovered a novel frameshift variant associated with presentations that cast a new light on the clinical features of CHILD syndrome.

Clinical Features and Predictors of Dysplasia in Proximal Sessile Serrated Lesions.

BACKGROUND/AIMS: Proximal colorectal cancers (CRCs) account for up to half of CRCs. Sessile serrated lesions (SSLs) are precursors to CRC. Proximal location and presence of dysplasia in SSLs predict higher risks of progression to cancer. The prevalence of dysplasia in proximal SSLs (pSSLs) and clinical characteristics of dysplastic pSSLs are not well studied. METHODS: Endoscopically resected colonic polyps at our center between January 2016 and December 2017 were screened for pSSLs. Data of patients with at least one pSSL were retrieved and clinicopathological features of pSSLs were analysed. pSSLs with and without dysplasia were compared for associations. RESULTS: Ninety pSSLs were identified, 45 of which had dysplasia giving a prevalence of 50.0%. Older age (65.9 years vs. 60.1 years, p=0.034) was associated with the presence of dysplasia. Twelve pSSLs were 10 mm or larger. After adjusting for age, pSSLs ≥10 mm had an adjusted odds ratio of 5.98 (95% confidence interval, 1.21-29.6) of having dysplasia compared with smaller pSSLs. CONCLUSION: In our cohort of pSSLs, the prevalence of dysplasia is high at 50.0% and is associated with lesion size ≥10 mm. Endoscopic resection for all proximal serrated lesions should be en-bloc to facilitate accurate histopathological examination for dysplasia as its presence warrants shorter surveillance intervals.

Impact of enhanced personal protective equipment on colonoscopy performance during the COVID-19 pandemic.

Background and study aims Using personal protective equipment (PPE) can reduce risk of disease transmission. During the COVID-19 pandemic, enhanced PPE (EPPE) is recommended when performing endoscopy. We aimed to evaluate the impact of EPPE on colonoscopy performance when compared to standard PPE (SPPE). Patients and methods A review of electronic medical records and endoscopy reports of consecutive patients who underwent colonoscopy during two similar one-month time periods (in 2019 and during the COVID-19 pandemic in 2020) was performed. SPPE was used in 2019 and EPPE was used in 2020. Patient clinical data and procedure-related information were captured and analyzed. The primary outcomes were time to cecum (TTC) and total procedure time. Secondary outcomes were adenoma detection rate (ADR), polyp detection rate (PDR) and cecal intubation rate (CIR). Statistical analysis was performed using STATA v16.1. Results Two hundred and forty-seven colonoscopy procedures were analyzed. Baseline demographics and indications for colonoscopy of patients in both groups were similar. There were no significant differences in median TTC (10.0 vs 10.0 min, P  = 0.524) or total procedure time (22.5 vs 23.0 min, P  = 0.946) between colonoscopy performed in SPPE and EPPE. The ADR, PDR and CIR were also similar. Conclusion Our findings suggest that use of EPPE does not affect colonoscopy performance.

A prospective randomized study of colonoscopy using blue laser imaging and white light imaging in detection and differentiation of colonic polyps.

Background and study aims Published data on blue laser imaging (BLI) for detection and differentiation of colonic polyps are limited compared to narrow band imaging (NBI). This study investigated whether BLI can increase the detection rate of colonic polyps and adenomas when compared to white light imaging (WLI), and examined use of NICE (NBI International Colorectal Endoscopic) and JNET (Japan NBI Expert Team) classifications with BLI. Patients and methods Patients aged 50 years and above referred for colonoscopy were randomized to BLI or WLI on withdrawal. Detected polyps were characterized using NICE and JNET classifications under BLI mode and correlated with histology. Primary outcome was adenoma detection rate. Secondary outcomes were utility of NICE and JNET classifications to predict histology using BLI. Results A total of 182 patients were randomized to BLI (92) or WLI (90). Comparing BLI with WLI, the polyp detection rate was 59.8 % vs 40.0 %, P  = 0.008, and the adenoma detection rate was 46.2 % vs 27.8 %, P  = 0.010. NICE 1 and JNET 1 diagnosed hyperplastic polyps with sensitivity of 87.18 % and specificity of 84.35 %. NICE 2 diagnosed low- (LGD) or high-grade dysplasia (HGD) with sensitivity of 92.31 % and specificity of 77.45 %. JNET 2A diagnosed LGD with sensitivity of 91.95 %, and specificity of 74.53 %. Four cases of focal HGD all had JNET 2A morphology. Conclusion BLI increased adenoma detection rate compared to WLI. NICE and JNET classifications can be applied when using BLI for endoscopic diagnosis of HP and LGD but histological confirmation remains crucial.

The difference in histological yield between 19G EUS-FNA and EUS-fine-needle biopsy needles.

BACKGROUND AND OBJECTIVE: EUS-guided fine-needle biopsy (EUS-FNB) with acquisition of tissue core is possible with the use of 19G fine-needle aspiration (FNA) and dedicated biopsy needles. Published data of direct comparisons between biopsy needles are more limited compared to the abundant data comparing EUS-FNA with EUS-FNB. We performed a retrospective study to determine the difference in histologic yield between 19G FNA needle and EUS-FNB needles in patients with solid masses. MATERIALS AND METHODS: Consecutive patients who underwent EUS-FNB of solid masses from January 2014 to July 2018 were identified from a database. The difference in histologic yield between needles was analyzed. RESULTS: A total of 159 patients underwent 179 EUS-FNB procedures (median of 2 needle passes [range: 1-4]). The use of 19G FNA, 19G, 20G, and 22G FNB needles allowed acquisition of a histologic core in 67.4% (29/43), 72.5% (29/40), 82.1% (46/56), and 75.9% (22/29), respectively (P = 0.368). A significant difference in the yield of histologic core was detected when 19G FNA needle was compared with 22G Acquire™ FNB needle (67.4% [29/43] vs. 94.1% [16/17], P = 0.032). The presence of histologic core was significantly associated with a positive diagnosis (95.6% vs. 30.2%, P < 0.0001). CONCLUSION: EUS-FNB with acquisition of histologic core improved the diagnostic yield. Dedicated FNB needles appeared to achieve a higher yield of histologic core compared to 19G FNA needles.

Endoscopic submucosal dissection of colorectal neoplasms: an audit of its safety and efficacy in a single tertiary centre in Singapore.

INTRODUCTION: Endoscopic submucosal dissection (ESD) provides a higher en bloc and R0 resection rate than endoscopic mucosal resection. Colorectal ESD is not widely used because of its technical difficulty and risk of complications, especially for right-sided colonic lesions. We audited the clinical outcomes of our initial experience with colorectal ESD. METHODS: We reviewed data collected from a prospective registry of patients who underwent colorectal ESD from December 2014 to March 2018. Therapeutic outcomes and procedure-related complications were analysed. RESULTS: A total of 41 patients (mean age 67.4 years, 21 male) underwent colorectal ESD. The distribution of the lesions was as follows: rectum (n = 9), sigmoid colon (n = 8), descending colon (n = 6), splenic flexure (n = 1), transverse colon (n = 5), ascending colon (n = 8) and caecum (n = 4). The mean size was 23 (range 12-50) mm. En bloc resection was achieved in 35 (85.4%) out of 41 patients, and R0 resection or clear resection margins was achieved in 33 (94.3%) of the en bloc resection patients. The lesion was upstaged in 14 (34.1%) patients after ESD. Colonic perforation occurred in 3 (7.3%) patients during ESD and was successfully treated with endoscopic clips. There was no procedure-related bleeding. No patient required surgery for management of complications. The median duration of hospitalisation was 1 (range 0-7) day. Four patients with lesions that were upstaged after ESD, from high-grade dysplasia to intramucosal carcinoma with deep submucosal invasion, were referred for colectomy. CONCLUSION: Our early outcome data was comparable to that from large published series. ESD is an effective and feasible treatment for colorectal lesions.

Safety and efficacy of SpyGlass cholangiopancreatoscopy in routine clinical practice in a regional Singapore hospital.

INTRODUCTION: This study examined the efficacy and safety of cholangiopancreatoscopy via the SpyGlass™ system in routine clinical practice. METHODS: The clinical data of endoscopic retrograde cholangiopancreatography (ERCP) performed in a regional hospital from January 2013 to November 2016 was retrieved from an electronic database and reviewed. All patients who had undergone SpyGlass cholangiopancreatoscopy were enrolled. Patient demographics, procedure indication, technical success rates, clinical success rates and complication rates were analysed. A subanalysis of clinical outcomes was performed comparing the SpyGlass legacy (fibreoptic) and digital systems. RESULTS: Out of 2,050 ERCP procedures performed, 47 patients underwent 50 cholangiopancreatoscopy procedures. Clinical indications were difficult common bile duct (CBD) stones (59.6%, n = 28), indeterminate CBD stricture (36.2%, n = 17), indeterminate pancreatic duct stricture (2.1%, n = 1) and proximally migrated CBD stent (2.1%, n = 1). Complete stone extraction was achieved in 26 (92.9%) out of 28 patients. Among patients with strictures, a correct diagnosis of malignancy based on image visualisation was achieved in all 11 cases. The sensitivity and specificity for SpyBite™ biopsies were 81.8% (95% confidence interval [CI] 48.2%-97.7%) and 100.0% (95% CI 15.8%-100.0%), respectively. The proximally migrated CBD stent was successfully extracted. Complications included pancreatitis (2.1%, n = 1), suspected sealed perforation after laser lithotripsy treated conservatively (2.1%, n = 1) and cholangitis (10.6%, n = 5). There was no difference in clinical outcomes between the SpyGlass legacy (n = 20) and digital (n = 30) systems. CONCLUSION: SpyGlass cholangiopancreatoscopy is a safe and effective tool in routine clinical practice.

Diagnostic Endoscopic Ultrasound: Technique, Current Status and Future Directions.

Endoscopic ultrasound (EUS) is now well established as an important tool in clinical practice. From purely diagnostic imaging, it has progressed to include tissue acquisition, which provided the basis for therapeutic procedures. Even as interventional EUS developed, there has been ongoing progress in EUS diagnostic capabilities due to improved imaging systems, better needles for tissue acquisition and development of enhanced imaging functions such as contrast harmonic EUS (CHEUS) and EUS elastography. EUS is well established for differentiation of subepithelial lesions, for T-staging of luminal gastrointestinal and pancreaticobiliary malignancies, for differentiation of benign pancreaticobiliary disorders and for diagnostic tissue acquisition, which can be achieved by EUS-guided fine needle aspiration or by EUS-guided fine needle biopsy using dedicated biopsy needles. This review briefly describes the technique of performing EUS and then discusses its clinical utility in terms of gastrointestinal cancer staging, the evaluation of pancreaticobiliary disorders and tissue acquisition. Enhanced imaging techniques such as CHEUS and EUS elastography are briefly reviewed.

The learning curve for needle knife precut sphincterotomy revisited.

BACKGROUND: There is no consensus on what constitutes adequate training for needle knife precut sphincterotomy. OBJECTIVE: The purpose of this study was to determine the number of procedures required before effective and safe precut sphincterotomy can be achieved. METHODS: This retrospective study examined the cumulative experience of a single endoscopist from January 2006-December 2015. Precut sphincterotomy success and complication rates were analyzed as a function of number of procedures performed. Acceptable success and complication rates were defined as 85% and 10% respectively. A one-sided binomial test was used to test success and complication rates of every 25 precut sphincterotomies performed. RESULTS: The index endoscopic retrograde cholangiopancreatography was successful in 141/158 (89.2%) patients who underwent precut sphincterotomy. This increased to 148/158 (93.7%) when endoscopic retrograde cholangiopancreatography was repeated on another day. Six precut sphincterotomies were required to achieve an 85% success probability. This was maintained consistently above 85% after 13 precuts, and was significantly higher (91.2%; p = 0.029) than 85% at the 125th precut. Bleeding and pancreatitis developed in 2/158 (1.3%) and 5/158 (3.2%). Probability of either complications remained below 5% after 50 precuts. No perforation occurred. CONCLUSION: At least 13 precut sphincterotomies were required to achieve a sustained success rate greater than 85%. The probability of bleeding or pancreatitis was less than 5% after 50 precut sphincterotomies.

Efficacy of small-volume simethicone given at least 30 min before gastroscopy.

AIM: To evaluate the efficacy of 5 mL simethicone solution in decreasing gastric foam if given at least 30 min before gastroscopy. METHODS: This was a randomized, placebo controlled, endoscopist blinded study performed at Changi General Hospital. Patients were at least 21 years old, had no prior surgical resection of the upper gastrointestinal tract, and scheduled for elective diagnostic gastroscopies. The primary outcome was the total mucosal visibility score (TMVS) which was evaluated using McNally score. The sample size was calculated to be 24 per group (SD 2.4, 80% power, P < 0.05, 2-sample t test). RESULTS: Fifty-four patients were randomised to receive either simethicone [1 mL liquid simethicone (100 mg) in 5 mL of water] or placebo (5 mL of water) at least 30 min before their gastroscopy. Six accredited consultants conducted the gastroscopy, and the interobserver agreement of scoring TMVS was good with a Kappa statistic of 0.73. The simethicone group had significantly better mean TMVS compared to placebo (5.78 ± SD 1.65 vs 8.89 ± SD 1.97, P < 0.001). The improvement was statistically significant for the duodenum and the gastric antrum, angularis, body, and fundus. Percent 51.9 of patients in the simethicone group had a TMVS of 4 (no bubbles at all) to 5 (only 1 area with minimal bubbles), while in the placebo group 3.7% of patients had TMVS of 4 or 5. The number needed to treat was 2.1 to avoid a TMVS of 6 and more. The simethicone group also had a significantly shorter procedure time with less volume of additional flushes required during gastroscopy to clear away obscuring gastric foam. CONCLUSION: With a premedication time of at least 30 min, 5 mL simethicone can significantly decrease gastric foam, decrease the volume of additional flushes, and shorten gastroscopy time.

A two-center comparative study of plastic and lumen-apposing large diameter self-expandable metallic stents in endoscopic ultrasound-guided drainage of pancreatic fluid collections.

BACKGROUND AND OBJECTIVES: Endoscopic ultrasound-guided drainage of walled-off pancreatic fluid collections (PFCs) (pseudocyst [PC]; walled-off necrosis [WON]) utilizes double pigtail plastic stents (PS) and the newer large diameter fully covered self-expandable stents (FCSEMS) customized for PFC drainage. This study examined the impact of type of stent on clinical outcomes and costs. PATIENTS AND METHODS: Retrospective two-center study. Outcome variables were technical and clinical success, need for repeat procedures, need for direct endoscopic necrosectomy (DEN), and procedure-related costs. RESULTS: A total of 49 (PC: 31, WON: 18) patients were analyzed. Initially, PS was used in 37 and FCSEMS in 12. Repeat transmural drainage was required in 14 (PS: 13 [9 treated with PS, 4 treated with FCSEMS]; FCSEMS: 1 [treated with PS]) due to stent migration (PS: 3; FCSEMS: 1) or inadequate drainage (PS: 10). Technical success was 100%. Initial clinical success was 64.9% (25/38) for PS versus 91.7% (11/12) for FCSEMS (P = 0.074). With repeat transmural stenting, final clinical success was achieved in 94.6% and 100%, respectively (P = 0.411). Compared to FCSEMS, PS was associated with greater need for repeat drainage (34.2% vs. 6.3%, P = 0.032). The need for and frequency of DEN was similar between both groups, but PS required more frequent balloon dilatation. PS was significantly cheaper for noninfected PC. Costs were similar for infected PC and WON. CONCLUSION: PS was associated with a higher need for a second drainage procedure to achieve clinical success. The use of FCSEMS did not increase procedural costs for infected PC and WON.

Comparative study of strategies for preventing post-ERCP pancreatitis after early precut sphincterotomy for biliary access.

OBJECTIVE: Needle knife precut sphincterotomy (PS) during endoscopic retrograde cholangiopancreatography (ERCP) has been associated with a high risk of post-ERCP pancreatitis (PEP). This study aimed to examine the effect of no prophylaxis, somatostatin, rectal diclofenac and pancreatic duct (PD) stenting in reducing rates of PEP in patients who underwent early PS. METHODS: This was a retrospective comparative study and the study period was from January 2006 to December 2015. A standardized approach to early PS was used: (i) inadvertent guidewire cannulation of the PD > thrice; (ii) impacted bile duct stone; (iii) inability to achieve deep cannulation within 10 min. PEP prophylactic measures included: (i) none when there was minimal papilla trauma; (ii) somatostatin infusion; (iii) rectal diclofenac; (iv) PD stent. The difference in rates of PEP between the different strategies was analysed. RESULTS: During the study period, PS was performed in 191 ERCP patients (mean age 66 years; 56.5% males). The ERCP success rate after PS was 93.2% (178/191). Overall the PEP rate was 3.1% (6/191) and the severity in all cases was mild. PEP occurred in 6.1% of patients with PD cannulation but not in those without (P = 0.016). PEP rates were 1.8%, 7.3%, 1.8% and 0% in control, somatostatin, diclofenac and PD stenting groups, respectively (P = 0.209). CONCLUSIONS: There was no significant difference in PEP rates after early PS whether or not prophylactic measures were adopted if there was minimal papilla trauma. A trend towards lower PEP rates was observed in patients who had either rectal diclofenac or PD stenting, compared to somatostatin.

The Changing Profile of Helicobacter pylori Antibiotic Resistance in Singapore: A 15-Year Study.

BACKGROUND: Antibiotic resistance is an important cause of H. pylori treatment failure. This study aimed to examine the change in H. pylori antibiotic resistance profile in Singapore over the course of 15 years. MATERIALS AND METHODS: The study period was from 2000 to 2014. Gastric mucosal biopsies obtained from H. pylori-positive patients were cultured. Antibiotic susceptibility to metronidazole, clarithromycin, levofloxacin, tetracycline, and amoxicillin was tested. The change in resistance rates over time was analyzed. RESULTS: A total of 708 H. pylori isolates were cultured. There was a significant increase in resistance rates for metronidazole (2000-2002: 24.8%; 2012-2014: 48.2%; p < .001), clarithromycin (2000-2002: 7.9%; 2012-2014: 17.1%; p = .022), and levofloxacin (2000-2002: 5%; 2012-2014: 14.7%; p = .007). The resistance rates for tetracycline (2000-2002: 5%; 2012-2014: 7.6%) and amoxicillin (2000-2002: 3%; 2012-2014: 4.4%) remained stable. Increase in dual (2000-2002: 6.9%; 2012-2014: 9.4%; p = .479) and triple antibiotic resistance rates (2000-2002: 0; 2012-2014: 7.6%; p < .001) were observed. Overall, the most common dual and triple resistance patterns were metronidazole/clarithromycin (4.4%) and metronidazole/clarithromycin/levofloxacin (1.8%), respectively. CONCLUSIONS: Over 15 years, H. pylori resistance rates to metronidazole, clarithromycin and levofloxacin had increased. There was increased resistance to multiple antibiotics.

A multicenter randomized comparison between high-definition white light endoscopy and narrow band imaging for detection of gastric lesions.

OBJECTIVE: Narrow band imaging (NBI) is generally considered to be useful for lesion characterization, but not enhanced detection of gastric lesions, because of the dark endoscopic view. We tested whether the new generation of NBI (190-NBI or 290-NBI), which is twice as bright as the previous version, would improve detection of premalignant gastric lesions compared with high-definition white light endoscopy (HD-WLE). PATIENTS AND METHODS: This was a multicenter prospective randomized study involving five tertiary institutions in the Asia-Pacific region. A total of 579 patients aged older than 50 years who underwent diagnostic upper gastrointestinal endoscopy were randomized to either HD-WLE or NBI. The outcome measurements were detection of intestinal metaplasia (IM), focal gastric lesions, and gastric cancers. RESULTS: Focal gastric lesions were detected in 83/286 (29%) and 119/293 patients (40.6%) by HD-WLE and by NBI, respectively (P=0.003). IM was detected in 22/286 patients (7.7%) by HD-WLE and in 52/293 patients (17.7%) by NBI (P<0.001). Gastric cancer were found in 7/286 (2.4%) and 3/293 patients (1%) in HD-WLE and NBI groups, respectively (P=0.189). CONCLUSION: NBI increased the detection rate of IM compared with HD-WLE.