A prospective randomized tandem gastroscopy pilot study of linked color imaging versus white light imaging for detection of upper gastrointestinal lesions.

BACKGROUND AND AIM: Gastrointestinal (GI) lesions may have subtle morphological changes. Linked color imaging (LCI) combines narrow-band wavelength light and white light imaging (WLI) in appropriate balance to enhance lesion detection. We compared the detection rates of upper GI lesions using LCI and WLI. METHOD: Patients were randomized in a 1:1 ratio to receive tandem gastroscopy with WLI inspection followed by LCI, or vice versa. Endoscopic examination was performed using the EG-L590ZW gastroscope and the LASEREO endoscope system (Fujifilm Co., Tokyo, Japan). Histology was reported by a specialist GI pathologist blinded to the technique of lesion detection and was used as the gold standard for diagnosis. RESULTS: Ninety patients (mean age 66.8 years, 51.5% male patients) were randomized to either LCI examination first followed by WLI (LCI-WLI), or vice versa (WLI-LCI). An 18.9% of gastroscopies in the study were for surveillance of previously known gastric cancer precursors. Ten patients (11.1%) had a history of Helicobacter pylori infection. There was no significant difference in the time taken for examination under LCI (311 ± 96 s) and WLI (342 ± 86 s) (P = 0.700). LCI detection rates were higher than WLI detection rates for gastric cancer precursors such as atrophic gastritis (2.19% vs 0.55%) (P < 0.01) and intestinal metaplasia (19.73% vs 7.67%) (P < 0.01). Both sensitivity (82.74% vs 50.96%) and specificity (98.71% vs 96.10%) of LCI were higher than WLI for detection of upper GI lesions. CONCLUSIONS: Linked color imaging had better detection rates, sensitivity, and specificity for detection of upper GI lesions compared with WLI.

Efficacy and safety of sofosbuvir/velpatasvir in a real-world chronic hepatitis C genotype 3 cohort.

BACKGROUND AND AIM: Real-world data on sofosbuvir/velpatasvir with and without ribavirin (SOF/VEL ± RBV), particularly among patients with genotype 3 (GT3) decompensated cirrhosis, prior treatment, coinfection, and hepatocellular carcinoma (HCC), are scarce. We aimed to assess the efficacy and safety of SOF/VEL ± RBV in a real-world setting that included both community and incarcerated GT3 hepatitis C virus (HCV) patients. METHODS: We included all GT3 HCV patients treated with SOF/VEL ± RBV in our institution. The primary outcome measure was the overall sustained virological response 12 weeks after treatment (SVR12), reported in both intention-to-treat (ITT) and per-protocol analyses. The secondary outcome measures were SVR12 stratified by the presence of decompensated cirrhosis, prior treatment, HCC, and HIV/hepatitis C virus coinfection and the occurrence rate of serious adverse events requiring treatment cessation or hospitalization. RESULTS: A total of 779 HCV patients were treated with 12 weeks of SOF/VEL ± RBV, of which 85% were treated during incarceration. Among the 530 GT3 HCV patients, 31% had liver cirrhosis, and 6% were treatment-experienced. The overall SVR12 for GT3 was 98.7% (95% confidence interval: 97.3%, 99.5%) and 99.2% (95% confidence interval: 98.1%, 99.8%) in ITT and per-protocol analyses, respectively. High SVR12 was also seen in ITT analysis among GT3 HCV patients with decompensated cirrhosis (88%), prior treatment (100%), HCC (100%), and HIV/hepatitis B virus coinfection (100%). Apart from one patient who developed myositis, no other serious adverse events were observed. CONCLUSION: The SOF/VEL ± RBV is a safe and efficacious treatment option for GT3 HCV patients in a real-world setting. SOF/VEL with RBV may be considered for decompensated GT3 HCV patients.

Randomized trial comparing effects of weight loss by liraglutide with lifestyle modification in non-alcoholic fatty liver disease.

BACKGROUND & AIMS: We compared the effects of weight loss induced with the glucagon-like peptide-1 agonist liraglutide, with that of lifestyle modification, followed by weight maintenance after discontinuing intervention, in obese adults with non-alcoholic fatty liver disease (NAFLD). METHODS: Thirty obese (mean age 40.7 ± 9.1 years, BMI 33.2 ± 3.6 kg/m2 , 90% male) adults with NAFLD defined as liver fat fraction (LFF) > 5% on magnetic resonance imaging without other causes of hepatic steatosis were randomized to a supervised programme of energy restriction plus moderate-intensity exercise to induce ≥ 5% weight loss (DE group, n = 15), or liraglutide 3 mg daily (LI group, n = 15) for 26 weeks, followed by 26 weeks with only advice to prevent weight regain. RESULTS: Diet and exercise and LI groups had significant (P < 0.01) and similar reductions in weight (-3.5 ± 3.3 vs -3.0 ± 2.2 kg), LFF (-8.1 ± 13.2 vs -7.0 ± 7.1%), serum alanine aminotransferase (-39 ± 35 vs -26 ± 33 U/L) and caspase-cleaved cytokeratin-18 (cCK-18) (-206 ± 252 vs -130 ± 158 U/L) at 26 weeks. At 52 weeks, the LI group significantly (P < 0.05) regained weight (1.8 ± 2.1 kg), LFF (4.0 ± 5.3%) and cCK-18 (72 ± 126 U/L), whereas these were unchanged in the DE group. CONCLUSIONS: Liraglutide was effective for decreasing weight, hepatic steatosis and hepatocellular apoptosis in obese adults with NAFLD, but benefits were not sustained after discontinuation, in contrast with lifestyle modification. Continuing the exercise learned in the structured programme contributed to the maintenance of liver fat reduction.

Comparative effects of liraglutide 3 mg vs structured lifestyle modification on body weight, liver fat and liver function in obese patients with non-alcoholic fatty liver disease: A pilot randomized trial.

We compared the effects of weight loss induced by the glucagon-like peptide 1-agonist liraglutide with a structured lifestyle intervention in obese adults with non-alcoholic fatty liver disease (NAFLD). Obese (body mass index ≥30 kg/m2 , mean weight 96.0 ± 16.3 kg) non-diabetic Asian adults, with NAFLD diagnosed by liver fat fraction (LFF) ≥ 5.5% on magnetic resonance imaging without other causes of hepatic steatosis, were randomized to a supervised program of dieting (restriction by 400 kilocalories/d) plus moderate-intensity aerobic exercise (~200 min/wk; DE group, n = 12), or liraglutide at the 3 mg daily dose approved for weight loss (LI group, n = 12), for 26 weeks. Both DE and LI groups had significant (P < .01) and similar reductions in weight (-3.5 ± 3.3 vs -3.5 ± 2.1 kg, respectively, P = .72), LFF (-8.9 ± 13.4 vs -7.2% ± 7.1%, P = .70), serum alanine aminotransferase (-42 ± 46 vs -34 ± 27 U/L, P = .52) and aspartate aminotransferase (-23 ± 24 vs -18 ± 15 U/L, P = .53). In this first randomized study comparing the 2 weight-loss modalities for improving NAFLD, liraglutide was as effective as structured lifestyle modification.

Asia-Pacific consensus on the management of gastro-oesophageal reflux disease: an update focusing on refractory reflux disease and Barrett's oesophagus.

OBJECTIVE: Since the publication of the Asia-Pacific consensus on gastro-oesophageal reflux disease in 2008, there has been further scientific advancement in this field. This updated consensus focuses on proton pump inhibitor-refractory reflux disease and Barrett's oesophagus. METHODS: A steering committee identified three areas to address: (1) burden of disease and diagnosis of reflux disease; (2) proton pump inhibitor-refractory reflux disease; (3) Barrett's oesophagus. Three working groups formulated draft statements with supporting evidence. Discussions were done via email before a final face-to-face discussion. We used a Delphi consensus process, with a 70% agreement threshold, using Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria to categorise the quality of evidence and strength of recommendations. RESULTS: A total of 32 statements were proposed and 31 were accepted by consensus. A rise in the prevalence rates of gastro-oesophageal reflux disease in Asia was noted, with the majority being non-erosive reflux disease. Overweight and obesity contributed to the rise. Proton pump inhibitor-refractory reflux disease was recognised to be common. A distinction was made between refractory symptoms and refractory reflux disease, with clarification of the roles of endoscopy and functional testing summarised in two algorithms. The definition of Barrett's oesophagus was revised such that a minimum length of 1 cm was required and the presence of intestinal metaplasia no longer necessary. We recommended the use of standardised endoscopic reporting and advocated endoscopic therapy for confirmed dysplasia and early cancer. CONCLUSIONS: These guidelines standardise the management of patients with refractory gastro-oesophageal reflux disease and Barrett's oesophagus in the Asia-Pacific region.

The impact of unrestricted access to direct-acting antiviral among incarcerated hepatitis C virus-infected patients.

BACKGROUND/AIMS: Despite the disproportionally high prevalence rates of hepatitis C virus (HCV) amongst the incarcerated population, eradication remains challenging due to logistic and financial barriers. Although treatment prioritization based on disease severity is commonly practiced, the efficacy of such approach remained uncertain. We aimed to compare the impact of unrestricted access to direct-acting antiviral (DAA) among incarcerated HCV-infected patients in Singapore. METHODS: In this retrospective study, we reviewed all incarcerated HCV-infected patients treated in our hospital during the restricted DAA era (2013-2018) and unrestricted DAA access era (2019). Study outcomes included the rate of sustained virological response (SVR), treatment completion and treatment default. Subgroup analysis was performed based on the presence of liver cirrhosis, HCV genotype and HCV treatment types. RESULTS: A total of 1,001 HCV patients was followed-up for 1,489 person-year. They were predominantly male (93%) with genotype-3 HCV infection (71%), and 38% were cirrhotic. The overall SVR during the restricted DAA access era and unrestricted DAA access era were 92.1% and 99.1%, respectively. Unrestricted access to DAA exponentially improved the treatment access among HCV-infected patients by 460%, resulting in a higher SVR rate (99% vs. 92%, P=0.003), higher treatment completion rate (99% vs. 93%, P<0.001) and lower treatment default rate (1% vs. 9%, P<0.001). CONCLUSION: In this large cohort of incarcerated HCV-infected patients, we demonstrated that unrestricted access to DAA is an impactful strategy to allow rapid treatment up-scale in HCV micro-elimination.

The utility of narrow band imaging in improving the endoscopic diagnosis of gastroesophageal reflux disease.

BACKGROUND & AIMS: Narrow band imaging (NBI) facilitates mucosal surface evaluation and may improve the endoscopic diagnosis of gastroesophageal reflux disease (GERD). We investigated the utility of NBI in improving the endoscopic diagnosis of GERD when compared with conventional endoscopy. METHODS: A total of 107 subjects (nonerosive reflux disease [NERD], 36; erosive reflux disease [ERD], 41; controls, 30) were recruited prospectively. The mucosal morphology at the squamocolumnar junction (SCJ) in GERD and controls was visualized using conventional endoscopy and NBI. The main outcome measurements were as follows: (1) The differences in mucosal morphology at the SCJ between conventional endoscopy and NBI; and (2) the differences in mucosal morphology at the SCJ between GERD and controls with NBI. RESULTS: Micro-erosions, increased vascularity, and pit patterns at the SCJ not seen on conventional endoscopy were well seen with NBI. Compared with controls, ERD and NERD had a significantly higher prevalence of micro-erosions (ERD, 100%; NERD, 52.8%; controls, 23.3%), and increased vascularity (ERD, 95.1%; NERD, 91.7%; controls, 36.7%), but a lower prevalence of round pit pattern (ERD, 4.9%; NERD, 5.6%; controls, 70%). ERD and NERD were similar in terms of increased vascularity and pit patterns. Increased vascularity with absence of round pit pattern was useful to distinguish NERD from controls (sensitivity, 86.1%; specificity, 83.3%). Interobserver agreement was good for increased vascularity (kappa = 0.95) and micro-erosions (kappa = 0.89), but lower for pit pattern (kappa = 0.59). CONCLUSIONS: NBI enhanced mucosal morphology at the SCJ and appeared useful for improving the endoscopic diagnosis of GERD.

A pilot study to examine the association between human gut microbiota and the host's central obesity.

BACKGROUND AND AIM: Perturbance in the composition of human gut microbiota has been associated with metabolic disorders such as obesity, diabetes mellitus, and insulin resistance. The objectives of this study are to examine the effects of ethnicity, central obesity, and recorded dietary components on potentially influencing the human gut microbiome. We hypothesize that these factors have an influence on the composition of the gut microbiome. METHODS: Subjects of Chinese (n = 14), Malay (n = 10), and Indian (n = 11) ancestry, with a median age of 39 years (range: 22-70 years old), provided stool samples for gut microbiome profiling using 16S rRNA sequencing and completed a dietary questionnaire. The serum samples were assayed for a panel of biomarkers (interleukin-6, tumor necrosis factor alpha, adiponectin, cleaved cytokeratin 18, lipopolysaccharide-binding protein, and limulus amebocyte lysate). Central obesity was defined by waist circumference cut-off values for Asians. RESULTS: There were no significant differences in Shannon alpha diversity for ethnicity and central obesity and no associations between levels of inflammatory cytokines and obesity. The relative abundances of Anaerofilum (P = 0.02), Gemellaceae (P = 0.02), Streptococcaceae (P = 0.03), and Rikenellaceae (P = 0.04) were significantly lower in the obese group. From principle coordinate analysis, the effects of the intake of fiber and fat/saturated fat were in contrast with each other, with clustering of obese individuals leaning toward fiber. CONCLUSION: The study demonstrated that there were differences in the gut microbiome in obese individuals. Certain bacterial taxa were present in lower abundance in the group with central obesity. Fiber and fat/saturated fat diets were not the key determinants of central obesity.

TC-325 versus the conventional combined technique for endoscopic treatment of peptic ulcers with high-risk bleeding stigmata: A randomized pilot study.

OBJECTIVE: Preliminary studies on a new topical hemostatic agent, TC-325, have shown its safety and effectiveness in treating active upper gastrointestinal (GI) bleeding. However, to date there have been no randomized trials comparing TC-325 with the conventional combined technique (CCT). Our pilot study aimed to compare the efficacy and safety of TC-325 with those of CCT in treating peptic ulcers with active bleeding or high-risk stigmata. METHODS: This was a comparative randomized study of patients with upper GI bleeding who had Forrest class I, IIA or IIB ulcers. RESULTS: Altogether 20 patients with a mean age of 70 years (range 23-87 years) were recruited, including 16 men, with a mean hemoglobin of 97 g/L. Initial hemostasis was successful in 19 (95.0%) patients, including 90.0% (9/10) in the TC-325 group and 100% (10/10) in the CCT group. TC-325 monotherapy failed to stop bleeding in a patient with Forrest IB posterior duodenal wall ulcer. Rebleeding was seen in 33.3% (3/9) of the patients in the TC-325 group and 10.0% (1/10) in the CCT group. One patient required angio-embolization therapy while three had successful conventional endotherapy. Two patients from the TC-325 group had serious adverse events that were not procedure- or therapy-related. In patients with Forrest IIA or IIB ulcers, five received TC-325 monotherapy; none had rebleeding. CONCLUSIONS: Our pilot study showed that TC-325 has a tendency towards a higher rebleeding rate than CCT, when treating actively bleeding ulcers. Larger trials are necessary for definitive results.

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.

Simple clinical prognostic model for hepatocellular carcinoma in developing countries and its validation.

PURPOSE: More than 80% of hepatocellular carcinomas (HCCs) worldwide occur in developing countries, especially in Asia. It often presents at an advanced stage beyond treatment. In this circumstance, a simple prognostic model is useful. Previous prognostic models require radiologic and laboratory investigations that are not readily available in developing countries. Our aim is to formulate and then validate a simple clinical prognostic model for HCC in an Asian population using only clinical parameters and with serum alpha-fetoprotein (AFP) as the sole laboratory test. PATIENTS AND METHODS: Cox regression modeling was performed on several clinical parameters and serum AFP level in 397 patients with HCC who received only supportive care in Singapore. A later group of 324 HCC patients from an Asia-Pacific-wide randomized trial was then used to validate the model. RESULTS: Ascites, physical performance status, and serum AFP were independently predictive of survival. Cox analysis yielded a simple score based on these three variables that categorizes patients into low-, medium-, and high-risk groups with 6-month survivals of 43%, 21%, and 5%, respectively. The prospective validation data provided corresponding estimates of 33%, 15%, and 3% and give confirmation of the utility of the simple model. CONCLUSION: We have formulated and prospectively validated a simple prognostic score for untreated HCC that only requires a clinical evaluation for ascites and physical performance status and measurement of serum AFP. This simple model is particularly apt for developing country circumstances and can also be used to select patients for treatment trials.

Current status of functional gastrointestinal evaluation in clinical practice.

Neurogastroenterology and motility disorders of the gastrointestinal (GI) tract encompass a broad spectrum of diseases involving the GI tract and central nervous system. They have varied pathophysiology, clinical presentation and management, and make up a substantial proportion of outpatient clinic visits. Typically, patients experience persistent symptoms referable to the GI tract despite normal endoscopic and radiologic findings. An appropriate evaluation is thus important in the patient's care. Advances in technology and understanding of the disease pathophysiology have provided better insight into the physiological basis of disease and a more rational approach to patient management. While technological advances serve to explain patients' persistent symptoms, they should be balanced against the costs of diagnostic tests. This review highlights the GI investigative modalities employed to evaluate patients with persistent GI symptoms in the absence of a structural lesion, with particular emphasis on investigative modalities available locally and the clinical impact of such tools.

Wireless oesophageal pH monitoring: establishing values in a multiracial cohort of asymptomatic Asian subjects.

BACKGROUND: Wireless oesophageal (Bravo) readings in healthy European and American subjects show varied results. Values in Asians remain unstudied. AIMS: We performed Bravo studies in healthy Asians to determine if values differed from previously published and identified reflux parameters to differentiate healthy volunteers from patients. METHODS: Fifty healthy volunteers were recruited between August 2009 and August 2011 to undergo 48 h wireless pH monitoring. Bravo capsule was introduced transorally and placed 6 cm above the squamocolumnar junction. Acid reflux parameters were compared against 41 patients previously evaluated for non-erosive reflux disease. RESULTS: Five volunteers were excluded. Capsule dislodgement occurred in four and three volunteers on study days 1 and 2 respectively. Forty and 37 volunteers (73% male, mean age 33.0 ± 7.6 years) had interpretable readings at 24 and 48 h, respectively. Percentage of time oesophageal pH<4 in 37 volunteers who completed 48 h recordings was 1.6% (7.5%), 1.5% (6.3%) and 1.9% (5.8%) on days 1, 2 and overall study duration, respectively. CONCLUSION: Bravo readings in Asians differed from previously published. Percentage of time oesophageal pH<4 on day 2 and DeMeester score on day 2 (95th percentile 22.9) best discriminated healthy volunteers from patients.

Emergency complications of acute and chronic pancreatitis.

Acute pancreatitis is a common disease with a relatively high morbidity and mortality. In contrast, chronic pancreatitis is a recurrent disease with multiple potential complications that occasionally require urgent intervention. This article focuses on the emergency complications of acute and chronic pancreatitis that require urgent intervention. Recent developments in the diagnosis and management of such complications are discussed.

Rectal and colonic distension elicit viscerovisceral reflexes in humans.

Colonic transit is slowed in patients with disordered rectal evacuation, but the mechanism of this phenomenon is unclear. Our objective was to investigate rectocolonic inhibitory reflexes in humans to provide potential insight into patients with obstructed defecation. In 30 healthy subjects, a barostat-manometric assembly recorded colonic tone and phasic activity in the descending colon during rectal distension and recorded rectal tone during colonic distension. Phasic distensions were 8, 16, and 32 mmHg above balloon operating pressure, and staircase inflations were comprised of balloon inflation then deflation in 2-mmHg increments at 30-s intervals from 0 to 36 mmHg. Colonic balloon volumes increased to a similar extent during phasic rectal distensions 8, 16, and 32 mmHg above operating pressure, reflecting reduced colonic tone; balloon volumes also increased and phasic pressure activity decreased during staircase rectal distensions. In contrast, rectal balloon volume declined, reflecting increased tone during phasic and staircase colonic distensions. Thus rectal distension inhibited colonic motor activity, indicative of a viscerovisceral inhibitory reflex.

Validation of Rome II criteria for functional gastrointestinal disorders by factor analysis of symptoms in Asian patient sample.

BACKGROUND: It has been unclear as to whether the Rome II criteria could be applied to patients in the Asia region with functional gastrointestinal (GI) diseases. The aim of the present study was to determine if symptoms of Asian patients with functional gastrointestinal disorders formed groups which corresponded to the Rome II diagnostic criteria. METHODS: A modified English version of Talley's bowel disease questionnaire was developed in collaboration with various research teams in accordance with the Rome II criteria. This instrument was translated into the local languages of the following nine Asian regions: China, Hong Kong, Indonesia, Korea, Malaysia, Singapore, Taiwan, Thailand and Vietnam. From September to December 2001, newly enrolled outpatients attending 14 GI or medical clinics in these regions were invited to complete the questionnaire. From these respondents, patients with functional gastrointestinal disorders fulfilling the '12 weeks out of 12 months' criteria were separated for further analysis. Principal component factor analysis with varimax rotation was used to identify symptom clusters or factors. These factors were compared with the existing classification of functional GI diseases derived from the Rome II criteria. RESULTS: Factor analysis of symptoms from 1012 functional GI patients supported the Rome II classification of the following groups of functional GI disorders: diarrhea-predominant irritable bowel syndrome, functional constipation, functional dyspepsia, functional abdominal pain syndrome, functional heartburn, and functional vomiting. Functional diarrhea was combined with functional anorectal disorders, and globus merged with functional dysphagia into one factor. Some of the functional dyspepsia, abdominal bloating and belching symptoms were loaded into one factor. CONCLUSIONS: Factor analysis of symptoms from a sample of Asian patients with functional GI disorders partially supported the use of the Rome II classification.