John J. Kim

Causes of bleeding and outcomes in patients hospitalized with upper gastrointestinal bleeding.

Goals: To evaluate sources of upper gastrointestinal bleeding (UGIB) at an urban US hospital and compare them to sources at the same center 20 years ago, and to assess clinical outcomes related to source of UGIB. Background: Recent studies suggest changes in causes and outcomes of UGIB. Study: Consecutive patients with hematemesis, melena, and/or hematochezia undergoing upper endoscopy with an identified source at LA County+USC Medical Center from January 2005 to June 2011 were identified retrospectively. Results: Mean age of the 1929 patients was 52 years; 75% were male. A total of 1073 (55%) presented with hematemesis, 809 (42%) with melena alone, and 47 (2%) with hematochezia alone. The most common causes were ulcers in 654 patients (34%), varices in 633 (33%), and erosive esophagitis in 156 (8%), compared with 43%, 33%, and 2% in 1991. During hospitalization, 207 (10.7%) patients required repeat endoscopy for UGIB (10.6% for both ulcers and varices) and 129 (6.7%) died (5.2% for ulcers; 9.2% for varices). On multivariate analysis, hematemesis (OR=1.38; 95% CI, 1.04-1.88) and having insurance (OR=1.44; 95% CI, 1.07-1.94) were associated with repeat endoscopy for UGIB. Varices (OR=1.53; 95% CI, 1.05-2.22) and having insurance (OR=4.53; 95% CI, 2.84-7.24) were associated with mortality. Conclusion: Peptic ulcers decreased modestly over 2 decades, whereas varices continue as a common cause of UGIB at an urban hospital serving lower socioeconomic patients. Inpatient mortality, but not rebleeding requiring endoscopy, was higher with variceal than nonvariceal UGIB, indicating patients with variceal UGIB remain at risk of death from decompensation of underlying illness even after successful control of bleeding.

Helicobacter pylori eradication therapy for functional dyspepsia: Systematic review and meta-analysis

AIM To evaluate whether Helicobacter pylori (H. pylori) eradication therapy benefits patients with functional dyspepsia (FD). METHODS Randomized controlled trials (RCTs) investigating the efficacy and safety of H. pylori eradication therapy for patients with functional dyspepsia published in English (up to May 2015) were identified by searching PubMed, EMBASE, and The Cochrane Library. Pooled estimates were measured using the fixed or random effect model. Overall effect was expressed as a pooled risk ratio (RR) or a standard mean difference (SMD). All data were analyzed with Review Manager 5.3 and Stata 12.0. RESULTS This systematic review included 25 RCTs with a total of 5555 patients with FD. Twenty-three of these studies were used to evaluate the benefits of H. pylori eradication therapy for symptom improvement; the pooled RR was 1.23 (95%CI: 1.12-1.36, P < 0.0001). H. pylori eradication therapy demonstrated symptom improvement during long-term follow-up at ≥ 1 year (RR = 1.24; 95%CI: 1.12-1.37, P < 0.0001) but not during short-term follow-up at < 1 year (RR = 1.26; 95%CI: 0.83-1.92, P = 0.27). Seven studies showed no benefit of H. pylori eradication therapy on quality of life with an SMD of -0.01 (95%CI: -0.11 to 0.08, P = 0.80). Six studies demonstrated that H. pylori eradication therapy reduced the development of peptic ulcer disease compared to no eradication therapy (RR = 0.35; 95%CI: 0.18-0.68, P = 0.002). Eight studies showed that H. pylori eradication therapy increased the likelihood of treatment-related side effects compared to no eradication therapy (RR = 2.02; 95%CI: 1.12-3.65, P = 0.02). Ten studies demonstrated that patients who received H. pylori eradication therapy were more likely to obtain histologic resolution of chronic gastritis compared to those who did not receive eradication therapy (RR = 7.13; 95%CI: 3.68-13.81, P < 0.00001). CONCLUSION The decision to eradicate H. pylori in patients with functional dyspepsia requires individual assessment.

Delayed endoscopic retrograde cholangiopancreatography is associated with persistent organ failure in hospitalised patients with acute cholangitis.

Predictors of organ failure and the impact of early endoscopic retrograde cholangiopancreatography (ERCP) on outcomes in patients with acute cholangitis are unclear.

Cyanoacrylate spray for treatment of difficult-to-control GI bleeding

BACKGROUND Although endoscopic therapy is highly effective for control of GI bleeding, a small proportion of patients experience persistent bleeding and may require radiologic or surgical intervention. Experience with cyanoacrylate spray for treatment of difficult-to-control GI bleeding is limited. OBJECTIVE To evaluate the efficacy and safety of an endoscopic cyanoacrylate spray technique for treatment of difficult-to-control GI bleeding. DESIGN Case series. SETTING Two tertiary-care centers. PATIENTS This study involved consecutive patients with overt GI bleeding who were treated with n-butyl-2-cyanoacrylate spray during endoscopy for persistent bleeding despite conventional hemostatic therapies. INTERVENTION Cyanoacrylate spray. MAIN OUTCOME MEASUREMENTS Hemostasis, rebleeding, adverse events, and technical failure associated with cyanoacrylate spray. RESULTS Five patients were treated with cyanoacrylate spray during endoscopy for persistent bleeding (duodenal ulcer in 3, gastric vascular ectasia in 1, rectal postpolypectomy bleeding in 1) after failed conventional therapies. Immediate hemostasis and technical success were achieved in all patients. At a median follow-up of 42 days (range 38-120 days), 2 patients developed recurrent bleeding. One patient experienced rebleeding 2 days after the procedure, subsequently requiring radiographic intervention and surgery. Another patient had recurrent bleeding from a different bleeding source 18 days after the procedure. No adverse events attributed to the cyanoacrylate spray were observed. LIMITATIONS Small number of patients. CONCLUSION In patients with difficult-to-control GI bleeding failing conventional endoscopic therapies, cyanoacrylate spray was effective in achieving immediate hemostasis. Prospective studies with a larger number of patients to evaluate the role of the cyanoacrylate spray technique during endoscopy for GI bleeding are needed.

Randomized trial of 1-week versus 2-week intervals for endoscopic ligation in the treatment of patients with esophageal variceal bleeding.

The appropriate interval between ligation sessions for treatment of esophageal variceal bleeding is uncertain. The optimal interval would provide variceal eradication as rapidly as possible to lessen early rebleeding while minimizing ligation‐induced adverse events. We randomly assigned patients hospitalized with acute esophageal variceal bleeding who had successful ligation at presentation to repeat ligation at 1‐week or 2‐week intervals. Beta‐blocker therapy was also prescribed. Ligation was performed at the assigned interval until varices were eradicated and then at 3 and 9 months after eradication. The primary endpoint was the proportion of patients with variceal eradication at 4 weeks. Four‐week variceal eradication occurred more often in the 1‐week than in the 2‐week group: 37/45 (82%) versus 23/45 (51%); difference = 31%, 95% confidence interval 12%‐48%. Eradication occurred more rapidly in the 1‐week group (18.1 versus 30.8 days, difference = −12.7 days, 95% confidence interval −20.0 to −5.4 days). The mean number of endoscopies to achieve eradication or to the last endoscopy in those not achieving eradication was comparable in the 1‐week and 2‐week groups (2.3 versus 2.1), with the mean number of postponed ligation sessions 0.3 versus 0.1 (difference = 0.2, 95% confidence interval −0.02 to 0.4). Rebleeding at 4 weeks (4% versus 4%) and 8 weeks (11% versus 9%), dysphagia/odynophagia/chest pain (9% versus 2%), strictures (0% versus 0%), and mortality (7% versus 7%) were similar with 1‐week and 2‐week intervals. Conclusion: One‐week ligation intervals led to more rapid eradication than 2‐week intervals without an increase in complications or number of endoscopies and without a reduction in rebleeding or other clinical outcomes; the decision regarding ligation intervals may be individualized based on patient and physician preferences and local logistics and resources. (Hepatology 2016;64:549‐555)

Crosstalk between Inflammation and ROCK/MLCK Signaling Pathways in Gastrointestinal Disorders with Intestinal Hyperpermeability

The barrier function of the intestine is essential for maintaining the normal homeostasis of the gut and mucosal immune system. Abnormalities in intestinal barrier function expressed by increased intestinal permeability have long been observed in various gastrointestinal disorders such as Crohns disease (CD), ulcerative colitis (UC), celiac disease, and irritable bowel syndrome (IBS). Imbalance of metabolizing junction proteins and mucosal inflammation contributes to intestinal hyperpermeability. Emerging studies exploring in vitro and in vivo model system demonstrate that Rho-associated coiled-coil containing protein kinase- (ROCK-) and myosin light chain kinase- (MLCK-) mediated pathways are involved in the regulation of intestinal permeability. With this perspective, we aim to summarize the current state of knowledge regarding the role of inflammation and ROCK-/MLCK-mediated pathways leading to intestinal hyperpermeability in gastrointestinal disorders. In the near future, it may be possible to specifically target these specific pathways to develop novel therapies for gastrointestinal disorders associated with increased gut permeability.

Micro-inflammation in functional dyspepsia: A systematic review and meta-analysis

Functional dyspepsia (FD) is a gastrointestinal disorder of unknown etiology. Although micro‐inflammation appears to be important in the pathogenesis, studies evaluating immune activation in FD have been inconsistent. A systematic review of literature and meta‐analysis was performed to compare immunologic cell counts and cytokine levels in the mucosa and peripheral blood of individuals with FD and healthy controls. PubMed, Embase, and the Cochrane library were searched. Data on immunologic cell counts and cytokines levels among individuals with FD and control groups were extracted and compared by calculating standard mean differences (SMD). Thirty‐seven studies met the inclusion criteria. Mast cell (SMD = 0.94, 95%CI 0.26‐1.62, P = .007) and eosinophil counts (SMD = 0.36, 95%CI 0.06‐0.68, P = .03) in the stomach were increased, among individuals with FD compared to controls. Similarly, mast cell (SMD = 0.66, 95%CI 0.20‐1.13, P = 0.005) and eosinophil (SMD = 0.95, 95%CI 0.66‐1.24; P < .001) counts in the duodenum were also increased in those with FD compared to controls. In a subgroup analysis, elevated eosinophil counts in the duodenum were observed in both post‐prandial distress syndrome (SMD = 0.97, 95%CI 0.46‐1.47, P = .0002) and epigastric pain syndrome subtypes (SMD = 1.16, 95%CI 0.48‐1.83, P = .0008). No differences in mucosal intraepithelial lymphocyte, enterochromaffin cell, and neutrophil counts, as well as, peripheral interlukin‐6 (IL‐6) and IL‐10 levels were observed among individuals with FD and controls. Micro‐inflammation in the form of local immune cell infiltration, particularly eosinophils and mast cells, characterizes the pathogenesis of FD.

KRAS and TP53 mutations in inflammatory bowel disease-associated colorectal cancer: a meta-analysis

Although KRAS and TP53 mutations are common in both inflammatory bowel disease-associated colorectal cancer (IBD-CRC) and sporadic colorectal cancer (S-CRC), molecular events leading to carcinogenesis may be different. Previous studies comparing the frequency of KRAS and TP53 mutations in IBD-CRC and S-CRC were inconsistent. We performed a meta-analysis to compare the presence of KRAS and TP53 mutations among patients with IBD-CRC, S-CRC, and IBD without dysplasia. A total of 19 publications (482 patients with IBD-CRC, 4,222 with S-CRC, 281 with IBD without dysplasia) met the study inclusion criteria. KRAS mutation was less frequent (RR=0.71, 95%CI 0.56-0.90; P=0.004) while TP53 mutation was more common (RR=1.24, 95%CI 1.10-1.39; P<0.001) in patients with IBD-CRC compared to S-CRC. Both KRAS (RR=3.09, 95%CI 1.47-6.51; P=0.003) and TP53 (RR=2.15, 95%CI 1.07-4.31 P=0.03) mutations were more prevalent in patients with IBD-CRC compared to IBD without dysplasia. In conclusion, IBD-CRC and S-CRC appear to have biologically different molecular pathways. TP53 appears to be more important than KRAS in IBD-CRC compared to S-CRC. Our findings suggest possible roles of TP53 and KRAS as biomarkers for cancer and dysplasia screening among patients with IBD and may also provide targeted therapy in patients with IBD-CRC.

Impact of gluten consumption in patients with functional dyspepsia: A case–control study

Dietary factors and immune dysfunction may induce symptoms in patients with functional dyspepsia (FD). The aim of the study was to evaluate whether gluten consumption impacts symptom onset in patients with FD and to evaluate for possible histologic alterations in the duodenum of patients with FD.

Gastroenterologists' practice patterns for positive fecal occult blood test.

Goals: To evaluate gastroenterologists’ use of esophagogastroduodenoscopy (EGD) for positive fecal occult blood test (FOBT). Background: Colonoscopy is recommended when an FOBT performed for colorectal cancer screening is positive. Guidelines suggest no further evaluation if anemia and gastrointestinal (GI) symptoms are absent. Methods: Online surveys included 4 vignettes: positive FOBT in average-risk adults 50 years of age or older with/without iron-deficiency anemia and with/without upper GI symptoms. For each scenario, respondents were asked if they would perform colonoscopy only, EGD only, colonoscopy+EGD on same day, or colonoscopy followed by EGD on different day if colonoscopy was negative. Results: Surveys were returned by 778 (11%) of 7094 potential responders. In patients without anemia or upper GI symptoms, 65% performed colonoscopy only; 35% added EGD (9% same day, 25% different day). EGD was added in 91% with anemia, 96% with symptoms, and 100% with anemia+symptoms. In patients with positive FOBT alone (no symptoms or anemia), multivariate analysis revealed fear of litigation as the primary factor associated with adding EGD to colonoscopy (odds ratio=4.1; 95% confidence interval, 2.3-7.3). When EGD+colonoscopy were planned for positive FOBT, private practice was associated with performing EGD on a different day (odds ratio=6.3; 95% confidence interval, 2.9-13.5 for private versus academic setting). Conclusions: One third of gastroenterologists perform EGD in addition to colonoscopy for a positive FOBT alone. Fear of litigation is the most important factor in deciding whether to add EGD to colonoscopy. When both procedures are planned, they are more likely to be performed on different days in a private practice setting than in an academic setting.