Gastric Cancer Due to Chronic H. pylori Infection: What We Know and Where We Are Going.

Helicobacter pylori is an established cause of many gastrointestinal pathologies including peptic ulcer disease, gastritis, and gastric cancer. It is an entity that affects the global population, and its true nature has only been known since the 1980s. Although there is much known about H. pylori including its pathophysiology, detection, and eradication, resistance to current therapy models is common. This is problematic because untreated or inadequately treated H. pylori increases morbidity and mortality related to gastric cancer and peptic ulcer disease among others. In order to improve the treatment and reduce resistance, there is significant ongoing research identifying new detection and eradication methods for H. pylori. This review aims to highlight what has already been established regarding H. pylori's epidemiology, pathophysiology, detection, and treatment as well as the most current and novel research involving detection and treatment of H. pylori.

Validation of choledocholithiasis predictors from the "2019 ASGE Guideline for the role of endoscopy in the evaluation and management of choledocholithiasis."

BACKGROUND AND AIMS: Identifying patients likely to have CDL is an important clinical dilemma because endoscopic retrograde cholangiopancreatography (ERCP), carries a 5-7% risk of adverse events. The purpose of this study was to compare the diagnostic test performance of the 2010 and 2019 ASGE criteria used to help risk stratify patients with suspected CDL. METHODS: Consecutive patients evaluated for possible CDL from 2013 to 2019 were identified from surgical, endoscopic, and radiologic databases at a single academic center. Inclusion criteria included all patients who underwent ERCP and/or cholecystectomy with intraoperative cholangiogram (IOC) for suspected CDL. We calculated the diagnostic test performance of criteria from both guidelines and compared their discrimination using the receiver operator curve. Univariate and multivariate analysis was used to identify the strongest component predictors. RESULTS: 1098 patients [age 57.9 ± 19.0 years, 62.8% (690) F] were included. 66.3% (728) were found to have CDL on ERCP and/or IOC. When using the 2019 guidelines, the sensitivity, specificity, PPV, NPV, and accuracy are 65.8, 78.9, 86.3, 54.1, and 70.4%, respectively. Using the 2010 guidelines, the sensitivity, specificity, PPV, NPV, and accuracy are 50.5, 78.9, 82.5, 44.8, and 60.1%, respectively. The AUC for high-risk criteria using the 2019 guidelines [0.726 (0.695, 0.758)] was greater than for the 2010 guidelines [0.647 (0.614, 0.681)]. The key difference providing the increased discrimination was the inclusion of stones on any imaging modality, which increased the sensitivity to 55.0% from 29.1%. Not including CDL on imaging or cholangitis, a dilated CBD was the strongest individual predictor of CDL on multivariate analysis (OR 3.70, CI 2.80, 4.89). CONCLUSION: Compared to 2010, the 2019 high-risk criterion improves diagnostic test performance, but still performs suboptimally. Less invasive tests, such as EUS or MRCP, should be considered in patients with suspected CDL prior to ERCP.

Performance and Predictors of Migration of Partially and Fully Covered Esophageal Self-Expanding Metal Stents for Malignant Dysphagia.

BACKGROUND & AIMS: Self-expanding metal stents (SEMS) are routinely used to palliate malignant dysphagia. However esophageal SEMS can migrate or obstruct due to epithelial hyperplasia. The aim of this study was to evaluate the rates and factors predicting migration and obstruction, and the nutritional outcomes in partially covered (pc) vs. fully covered (fc) SEMS vs. fcSEMS with antimigration fins (AF) placed for malignant dysphagia. METHODS: A retrospective review of consecutive patients undergoing SEMS placement for malignant dysphagia at three academic medical centers. RESULTS: Among 357 patients, there were 55 (15.4%) stent migrations, 45 (12.6%) obstructions from epithelial hyperplasia, and 20 (5.6%) food impactions. Median overall survival was 79 days (IQR 41,199). The percent weight change/change in albumin at 30 and 60 days after SEMS placement were -2.24%/-0.544 g/dL and -2.98%/-0.55 g/dL, respectively. Stent migration occurred significantly more often with fcSEMS than pcSEMS (25.3% vs 10.9%; P < .003), but there was no difference when either group was compared to fcSEMS-AF (19.3%). The overall rate of epithelial hyperplasia resulting in stent obstruction was low (12.6%) and not different between stent types. Factors associated with increased risk of SEMS migration on multivariable logistic regression included stricture traversability with a diagnostic endoscope (OR, 2.37; 95% CI, 1.29-4.35) and use of fcSEMS (OR, 2.56; 1.31-5.00) or fcSEMS-AF (OR, 2.30, 1.03-5.14). CONCLUSIONS: Traversability of a malignant esophageal stenosis predicts SEMS migration. In these patients with a limited overall survival, pcSEMS are associated with lower rates of stent migration and similar rates of obstruction compared to fcSEMS.

Straight leg raise metrics on high-resolution manometry associate with esophageal reflux burden.

BACKGROUND: Straight leg raise (SLR) is a provocative maneuver that assesses esophagogastric junction (EGJ) barrier function during high-resolution manometry (HRM). We evaluated the value of SLR in symptomatic reflux patients undergoing ambulatory reflux monitoring. METHODS: Adult patients being evaluated for reflux symptoms with esophageal physiologic testing off antisecretory therapy over a 12 month period were studied. Demographics, clinical presentation, HRM studies, and reflux monitoring studies were analyzed. Intra-abdominal and intra-esophageal pressures were extracted at baseline and during SLR from HRM studies. Acid exposure time (AET) was derived from reflux monitoring studies, and EGJ morphology and tone from HRM studies. SLR pressure metrics predicting abnormal AET were evaluated. KEY RESULTS: Of 122 patients, 70 (57.4%) had ≥50% peak intra-abdominal pressure increase during SLR (58.0 ± 1.4 years, 75.7% female). Peak intra-esophageal pressure gradient between baseline and SLR predicted pathologic AET when ≥100% (AUC 0.78, sensitivity 71%, specificity 75%, P < .001), seen in 60.7% with AET > 6%, but only 23.7% with AET < 4% (P = .01). Peak intra-esophageal pressure gradient ≥100% was most discriminative in identifying abnormal acid burden in type 1 EGJ morphology (P = .005) but trended toward significance in type 2 and type 3 morphology (P = .1). Normal and abnormal EGJ contractile integral did not associate with peak intra-esophageal pressure gradient either collectively or when subdivided by EGJ morphology (P ≥ .2). CONCLUSIONS & INFERENCES: Analysis of intra-esophageal pressure gradients during SLR, a simple HRM maneuver, may augment evaluation of symptomatic GERD, and provide adjunctive evidence supporting GERD.

Trans-esophagogastric junction pressure gradients during straight leg raise maneuver on high-resolution manometry associate with large hiatus hernias.

BACKGROUND: Straight leg raise (SLR) while supine increases intra-abdominal pressure. We hypothesized that elevations in intra-abdominal pressure would transmit into the thoracic cavity if the esophagogastric junction (EGJ) was disrupted. METHODS: Consecutive patients undergoing esophageal HRM were included if they had adequate SLR (hip flexion with knees extended for ≥ 5 seconds while supine). EGJ morphology was subtyped based on lower esophageal sphincter (LES) and crural diaphragm (CD) location (type 1: LES and CD overlap; type 2: separation of < 3 cm; type 3: separation of ≥ 3 cm). EGJ tone was assessed using EGJ contractile integral (EGJ-CI). HRM studies were analyzed according to Chicago Classification v3.0. Mean and peak intra-thoracic and abdominal pressures were measured at baseline and during SLR using on-screen software tools. Trans-EGJ gradients were compared, and pressure gradient < 1 mmHg denoted the equalization of pressures. KEY RESULTS: Of 430 patients, 248 (57.5 ± 0.9 years, 69.4% F) completed SLR. EGJ morphology was type 1 in 122 (49.2%), type 2 in 56 (22.6%) and type 3 in 40 (16.1%). In types 1 and 2 EGJ, neither the mean nor peak trans-EGJ pressure gradient changed with SLR (P ≥ .17 for each). In contrast, in type 3 EGJ, peak pressure gradient decreased significantly following SLR (3.5 ± 1.8 mmHg vs. -8.6 ± 4.8 mmHg, P = .01). More type 3 EGJ patients equalized peak (65%) pressures across EGJ compared with types 1 and 2 (27%, P < .001). CONCLUSIONS AND INFERENCES: The evaluation of intra-abdominal and intra-thoracic pressures with SLR during esophageal HRM can provide evidence of physiological disruption of the EGJ barrier.

Prolonged Wireless pH Monitoring in Patients With Persistent Reflux Symptoms Despite Proton Pump Inhibitor Therapy.

BACKGROUND & AIMS: Wireless pH monitoring measures esophageal acid exposure time (AET) for up to 96 hours. We evaluated competing methods of analysis of wireless pH data. METHODS: Adult patients with persisting reflux symptoms despite acid suppression (n = 322, 48.5 ± 0.9 years, 61.7% women) from 2 tertiary centers were evaluated using symptom questionnaires and wireless pH monitoring off therapy, from November 2013 through September 2017; 30 healthy adults (control subjects; 26.9 ± 1.5 years; 60.0% women) were similarly evaluated. Concordance of daily AET (physiologic <4%, borderline 4%-6%, pathologic>6%) for 2 or more days constituted the predominant AET pattern. Each predominant pattern (physiologic, borderline, or pathologic) in relation to data from the first day, and total averaged AET, were compared with other interpretation paradigms (first 2 days, best day, or worst day) and with symptoms. RESULTS: At least 2 days of AET data were available from 96.9% of patients, 3 days from 90.7%, and 4 days from 72.7%. A higher proportion of patients had a predominant pathologic pattern (31.4%) than control subjects (11.1%; P = .03). When 3 or more days of data were available, 90.4% of patients had a predominant AET pattern; when 2 days of data were available, 64.1% had a predominant AET pattern (P < .001). Day 1 AET was discordant with the predominant pattern in 22.4% of patients and was less strongly associated with the predominant pattern compared with 48 hour AET (P = .059) or total averaged AET (P = .02). Baseline symptom burden was higher in patients with a predominant pathologic pattern compared with a predominant physiologic pattern (P = .02). CONCLUSIONS: The predominant AET pattern on prolonged wireless pH monitoring can identify patients at risk for reflux symptoms and provides gains over 24 hours and 48 hours recording, especially when results from the first 2 days are discordant or borderline.

Rectal Endoscopic Ultrasound in Clinical Practice.

PURPOSE OF REVIEW: Endoscopic ultrasound (EUS) is routinely utilized for evaluation of disorders of the lower gastrointestinal tract. In this review, we summarize the current status of rectal EUS in clinical practice and describe recent developments in diagnostic and therapeutic rectal EUS. RECENT FINDINGS: Recent guidelines recommend rectal EUS for rectal cancer staging as a second line modality in cases where MRI is contraindicated. Forward-viewing echoendoscopes and through the scope EUS miniprobes allow for EUS imaging of lesions through the entire colon and for evaluation beyond stenoses or luminal narrowings. EUS can be used to assess perianal disease and drain pelvic abscess associated with IBD, along with newer applications currently under investigation. For rectal varices, EUS can confirm the diagnosis, assess the optimal site for banding, guide therapy placement with sclerotherapy and/or coils, and assess response to treatment by confirming absence of flow. Therapeutic rectal EUS is emerging as a promising modality for drainage of pelvic fluid collection drainage and fiducial placement for rectal or prostatic cancer. Drug delivery mechanisms and substances that may increase the scope of therapy with rectal EUS are in varying stages of development. Rectal EUS continues to be an important modality for evaluation of benign and malignant disorders of the lower gastrointestinal tract, although its use as a cancer staging modality has declined due to improvements in MRI technology. Various technologies to enhance ultrasound imaging and for therapeutics have been developed that have or may contribute to expanded indications for rectal EUS.

Use of a Transparent Cap Increases the Diagnostic Yield in Antegrade Single-Balloon Enteroscopy for Obscure GI Bleed.

BACKGROUND AND AIMS: Single-balloon enteroscopy (SBE) is utilized in the evaluation of obscure gastrointestinal bleeding, but 40-50% of these patients experience continued GI blood loss, in part due to missed lesions. The utilization of a transparent cap attached to the end of the endoscope can improve mucosal visualization in other endoscopic applications, but has not yet been evaluated in SBE. The aim of this study was to evaluate the impact of a cap on the diagnostic yield of SBE. METHODS: Consecutive adult patients scheduled for anterograde SBE for the evaluation of obscure GI bleeding were screened for inclusion from 2014 to 2017. Patients were randomized to SBE with or without a transparent cap. The primary outcome was the proportion of enteroscopies in which a P2 lesion (high potential for bleeding) was identified. RESULTS: A total of 90 patients (65.7 ± 12.7 years old, 47.7% female) were analyzed. There were significantly more P2 arteriovenous malformations identified in the cap group (14.8% vs. 0%, p = 0.02). Additionally, the use of a cap was associated with a significantly greater depth of small bowel insertion (191.9 cm vs. 156.2 cm, p = 0.01). There was one perforation in the group without a cap, successfully treated with clip placement, and no adverse events in the cap group. CONCLUSIONS: The use of a transparent cap during SBE performed for the evaluation of obscure gastrointestinal bleeding may be an important, safe augmentation to standard SBE techniques.

Clinical Characteristics and Outcomes of Patients With Postfundoplication Dysphagia.

BACKGROUND & AIMS: Dysphagia is a consequence of antireflux surgery (ARS) for gastroesophageal reflux disease (GERD). We studied patient management and symptomatic outcomes. METHODS: We performed a retrospective study of 157 consecutive adult patients with GERD (mean age, 65.1 ± 1.0 y; 72% female) who underwent ARS at a tertiary care center from 2003 through 2014. We characterized postfundoplication dysphagia using a self-reported Likert scale, which ranged from a low score of 0 (no dysphagia) to a high score of 4 (severe daily dysphagia); scores of 2 or more indicated clinically significant dysphagia. Postfundoplication dysphagia was categorized as early (≤6 wk after ARS) or late (>6 wk after ARS), and Kaplan-Meier analyses were used to assess the time to development of clinically significant dysphagia. We performed univariate and multivariate analyses to assess management response and identify factors associated with dysphagia. The primary aim was to determine the prevalence and clinical course of postfundoplication dysphagia in patients with GERD treated with ARS. RESULTS: Of the 157 patients, 54.8% had early postfundoplication dysphagia (clinically significant in 20.4%); only 3.5% required endoscopic intervention. Over 2.1 ± 0.2 years of follow-up evaluation, 29 patients (18.5%) developed late postfundoplication dysphagia. Based on Kaplan-Meier analysis, the median time to clinically significant late postfundoplication dysphagia was 0.75 years (95% CI, 0.26-1.22). Of 13 patients (44.8%) who underwent endoscopic dilation, improvement was reported by 92.3%, with a mean decrease in dysphagia severity of 1.55 ± 0.3, based on the Likert scale. Prefundoplication dysphagia, early postfundoplication dysphagia, recurrent hiatal hernia, and lack of contraction reserve following multiple rapid swallows were univariate predictors of late postfundoplication dysphagia (P ≤ .04); lack of contraction reserve was associated independently with late postfundoplication dysphagia, based on multivariate logistic regression analysis (odds ratio, 3.73; 95% CI, 1.11-12.56). CONCLUSIONS: Early and late postfundoplication dysphagia can be successfully managed conservatively or with endoscopic dilation, respectively. Lack of contraction reserve on multiple rapid swallows is associated independently with late postfundoplication dysphagia.

Model to Select On-Therapy vs Off-Therapy Tests for Patients With Refractory Esophageal or Extraesophageal Symptoms.

BACKGROUND & AIMS: It is not clear whether we should test for reflux in patients with refractory heartburn or extraesophageal reflux (EER) symptoms, such as cough, hoarseness, or asthma. Guidelines recommend testing patients by pH monitoring when they are on or off acid-suppressive therapies based on pretest probability of reflux, determined by expert consensus. However, it is not clear what constitutes a low or high pretest probability of reflux in these patients. We aimed to develop a model that clinicians can use at bedside to estimate pretest probability of abnormal reflux. METHODS: We performed a prospective study of 471 adult patients with refractory heartburn (n = 214) or suspected EER symptoms (n = 257) who underwent endoscopy with wireless pH monitoring while they were off acid-suppressive treatment and assigned them to groups based on symptoms at presentation (discovery cohort). Using data from the discovery cohort, we performed proportional odds ordinal logistic regression to select factors (easy to obtain demographic criteria and clinical symptoms such as heartburn, regurgitation, asthma, cough, and hoarseness) associated with esophageal exposure to acid. We validated our findings in a cohort of 118 patients with the same features from 2 separate tertiary care centers (62% women; median age 59 years; 62% with cough as presenting symptom). RESULTS: Abnormal pH (>5.5% of time spent at pH <4) was found in 56% of patients with heartburn and 63% of patients with EER (P = .15). Within EER groups, abnormal pH was detected in a significantly larger proportion (80%) of patients with asthma compared with patients with cough (60%) or hoarseness (51%; P < .01). Factors significantly associated with abnormal pH in patients with heartburn were presence of hiatal hernia and body mass index >25 kg/m2. In patients with EER, the risk of reflux was independently associated with the presence of concomitant heartburn (odds ratio [OR] 2.0; 95% confidence interval [CI] 1.3-3.1), body mass index >25 kg/m2 (OR 2.1; 95% CI 1.5-3.1), asthma (OR 2.0; 95% CI 1.2-3.5), and presence of hiatal hernia (OR 1.9; 95% CI 1.2-3.1). When we used these factors to create a scoring system, we found that a score of ≤2 excluded patients with moderate to severe reflux, with a negative predictive value of 80% in the discovery cohort and a negative predictive value of 85% in the validation cohort. CONCLUSION: We developed a clinical model to estimate pretest probability of abnormal pH in patients who were failed by proton pump inhibitor therapy. This system can help guide clinicians at bedside in determining the most appropriate diagnostic test in this challenging group of patients.

Transpapillary drainage has no added benefit on treatment outcomes in patients undergoing EUS-guided transmural drainage of pancreatic pseudocysts: a large multicenter study.

BACKGROUND AND AIMS: The need for transpapillary drainage (TPD) in patients undergoing transmural drainage (TMD) of pancreatic fluid collections (PFCs) remains unclear. The aims of this study were to compare treatment outcomes between patients with pancreatic pseudocysts undergoing TMD versus combined (TMD and TPD) drainage (CD) and to identify predictors of symptomatic and radiologic resolution. METHODS: This is a retrospective review of 375 consecutive patients with PFCs who underwent EUS-guided TMD from 2008 to 2014 at 15 academic centers in the United States. Main outcome measures included TMD and CD technical success, treatment outcomes (symptomatic and radiologic resolution) at follow-up, and predictors of treatment outcomes on logistic regression. RESULTS: A total of 375 patients underwent EUS-guided TMD of PFCs, of which 174 were pseudocysts. TMD alone was performed in 95 (55%) and CD in 79 (45%) pseudocysts. Technical success was as follows: TMD, 92 (97%) versus CD, 35 (44%) (P = .0001). There was no difference in adverse events between the TMD (15%) and CD (14%) cohorts (P = .23). Median long-term (LT) follow-up after transmural stent removal was 324 days (interquartile range, 72-493 days) for TMD and 201 days (interquartile range, 150-493 days) (P = .37). There was no difference in LT symptomatic resolution (TMD, 69% vs CD, 62%; P = .61) or LT radiologic resolution (TMD, 71% vs CD, 67%; P = .79). TPD attempt was negatively associated with LT radiologic resolution of pseudocyst (odds ratio, 0.11; 95% confidence interval, 0.02-0.8; P = .03). CONCLUSIONS: TPD has no benefit on treatment outcomes in patients undergoing EUS-guided TMD of pancreatic pseudocysts and negatively affects LT resolution of PFCs.

Cyclic stretch affects pulmonary endothelial cell control of pulmonary smooth muscle cell growth.

Endothelial cells are subjected to mechanical forces in the form of cyclic stretch resulting from blood pulsatility. Pulmonary artery endothelial cells (PAECs) produce factors that stimulate and inhibit pulmonary artery smooth muscle cell (PASMC) growth. We hypothesized that PAECs exposed to cyclic stretch secrete proteins that inhibit PASMC growth. Media from PAECs exposed to cyclic stretch significantly inhibited PASMC growth in a time-dependent manner. Lyophilized material isolated from stretched PAEC-conditioned media significantly inhibited PASMC growth in a dose-dependent manner. This inhibition was reversed by trypsin inactivation, which is consistent with the relevant factor being a protein(s). To identify proteins that inhibited cell growth in conditioned media from stretched PAECs, we used proteomic techniques and found that thrombospondin (TSP)-1, a natural antiangiogenic factor, was up-regulated by stretch. In vitro, exogenous TSP-1 inhibited PASMC growth. TSP-1-blocking antibodies reversed conditioned media-induced inhibition of PASMC growth. Cyclic stretched PAECs secrete protein(s) that inhibit PASMC proliferation. TSP-1 may be, at least in part, responsible for this inhibition. The complete identification and understanding of the secreted proteome of stretched PAECs may lead to new insights into the pathophysiology of pulmonary vascular remodeling.