Performance of Endoscopic Ultrasound-Guided Versus Percutaneous Liver Biopsy in Diagnosing Stage 3-4 Fibrosis.

BACKGROUND: Percutaneous liver biopsy (P-bx) is the gold standard for diagnosing advanced fibrosis. Despite the proven technical feasibility of EUS-guided liver bx (EUS-bx) as a novel alternative way of liver biopsy, the clinical applicability remains to be determined. AIMS: The primary aim of this study is to evaluate if EUS-bx, compared to P-bx, can effectively and safely obtain adequate specimen and accurately predict hepatic fibrosis. METHODS: This is a single center, retrospective chart review among patients with liver diseases at a tertiary endoscopy center from February 2011 to March 2020. We assessed the EUS-bx versus P-bx outcomes by success rate, performance, and safety profile. The primary outcome was the association between EUS-bx clinical variables and the presence of histologic liver fibrosis stage ≥ 3. The secondary outcomes were the associations between EUS-bx and variables indicative of fibrosis. RESULTS: Fifty-nine patients underwent EUS-bx; and 59, P-bx. All EUS-bx procedures were successfully completed. All 56/56 (100%) of EUS-bx vs. 50/52 (96.2%) P-bx were considered adequate samples. Tissue lengths were significantly longer in the EUS-bx cohort (p < 0.0001) with a trend towards a greater number of portal tracts. 46/56 (82.1%) cases of EUS-bx vs. 32/52 (61.5%) of P-bx had > 10 portal tracts; 21/56 (37.5%) cases of EUS-bx vs. 14/52 (26.9%) of P-bx had > 15 portal tracts. There were 6 (10.2%) EUS-bx vs. 1 (1.7%) P-bx related complication leading to a phone call (p = 0.061). CONCLUSIONS: EUS-bx can safely performed and accurately predict liver fibrosis stage as the standard P-bx without being influenced by procedure-related factors.

Transoral incisionless fundoplication for recurrent symptoms after laparoscopic fundoplication.

BACKGROUND: Revision of a failed laparoscopic fundoplication carries higher risk of complication and lower chance of success compared to the original surgery. Transoral incisionless fundoplication (TIF) may be an endoscopic alternative for select GERD patients without need of a moderate/large hiatal hernia repair. The aim of this study was to assess feasibility, efficacy, and safety of TIF 2.0 after failed laparoscopic Nissen or Toupet fundoplication (TIFFF). METHODS: This is a multicenter retrospective cohort study of patients who underwent TIFFF between September 2017 and December 2020 using TIF 2.0 technique (EsophyX Z/Z+) performed by gastroenterologists and surgeons. Patients were included if they had (1) recurrent GERD symptoms, (2) pathologic reflux based upon pH testing or Grade C/D esophagitis or Barrett's esophagus, and (3) hiatal hernia ≤ 2 cm. The primary outcome was improvement in GERD Health-Related Quality of Life (GERD-HRQL) post-TIFFF. The TIFFF cohort was also compared to a similar surgical re-operative cohort using propensity score matching. RESULTS: Twenty patients underwent TIFFF (median 4.1 years after prior fundoplication) and mean GERD-HRQL score improved from 24.3 ± 22.9 to 14.75 ± 21.6 (p = 0.014); mean Reflux Severity Index (RSI) score improved from 14.1 ± 14.6 to 9.1 ± 8.0 (p = 0.046) with 8/10 (80%) of patients with normal RSI (< 13) post-TIF. Esophagitis healed in 78% of patients. PPI use decreased from 85 to 55% with 8/20 (45%) patients off of PPI. Importantly, mean acid exposure time decreased from 12% ± 17.8 to 0.8% ± 1.1 (p = 0.028) with 9/9 (100%) of patients with normalized pH post-TIF. There were no statistically significant differences in clinical efficacy outcomes between TIFFF and surgical revision, but TIFFF had significantly fewer late adverse events. CONCLUSION: Endoscopic rescue with TIF is a safe and efficacious alternative to redo laparoscopic surgery in symptomatic patients with appropriate anatomy and objective evidence of persistent or recurrent reflux.

Combination Topical Epinephrine and Non-steroidal Inflammatory Drugs in the Prevention of Post-ERCP Pancreatitis: A Systematic Review.

BACKGROUND: The utility of combination rectal NSAID and topical epinephrine (EI) or rectal NSAID and normal saline (SI) sprayed on duodenal papilla in the prevention of post-ERCP pancreatitis (PEP) has been studied but results have been conflicting. AIMS: To evaluate the benefit of using combination prophylaxis in preventing PEP. METHODS: A literature search was performed using Scopus, PubMed/MEDLINE, and Cochrane databases in May 2021. Randomized controlled trials (RCTs) involving adults patients who underwent ERCP and received EI versus SI were eligible for inclusion. The pooled effect was expressed as odds ratio (OR) to assess the rate of PEP, severity of PEP, and specific adverse events. The results were pooled using Reviewer Manager 5.4 software. RESULTS: Six RCTs involving 4016 patients were included in the final analysis. The EI group did not demonstrate any significant benefit over SI group in preventing PEP (OR = 1.00, 95% CI [0.68, 1.45], P = 0.98), irrespective of gender or the epinephrine concentration used. The tests for subgroup differences were not statistically significant with P-values of 0.66 and 0.28, respectively. The addition of topical epinephrine to rectal NSAID did not improve the rate of moderate to severe PEP (OR = 0.94, P = 0.86) or PEP in high-risk patients (OR = 1.14, 95%, P = 0.73). The rates of infection, including cholangitis and sepsis (OR = 0.63, P = 0.07), gastrointestinal bleeding (OR = 1.25, P = 0.56) and procedure-related death (OR = 0.71, P = 0.59) were similar between both groups. CONCLUSION: The addition of topical epinephrine did not demonstrate any benefit over rectal NSAID alone in preventing PEP or reducing other procedure-related adverse events.

A Comparison of Logistic Regression Against Machine Learning Algorithms for Gastric Cancer Risk Prediction Within Real-World Clinical Data Streams.

PURPOSE: Noncardia gastric cancer (NCGC) is a leading cause of global cancer mortality, and is often diagnosed at advanced stages. Development of NCGC risk models within electronic health records (EHR) may allow for improved cancer prevention. There has been much recent interest in use of machine learning (ML) for cancer prediction, but few studies comparing ML with classical statistical models for NCGC risk prediction. METHODS: We trained models using logistic regression (LR) and four commonly used ML algorithms to predict NCGC from age-/sex-matched controls in two EHR systems: Stanford University and the University of Washington (UW). The LR model contained well-established NCGC risk factors (intestinal metaplasia histology, prior Helicobacter pylori infection, race, ethnicity, nativity status, smoking history, anemia), whereas ML models agnostically selected variables from the EHR. Models were developed and internally validated in the Stanford data, and externally validated in the UW data. Hyperparameter tuning of models was achieved using cross-validation. Model performance was compared by accuracy, sensitivity, and specificity. RESULTS: In internal validation, LR performed with comparable accuracy (0.732; 95% CI, 0.698 to 0.764), sensitivity (0.697; 95% CI, 0.647 to 0.744), and specificity (0.767; 95% CI, 0.720 to 0.809) to penalized lasso, support vector machine, K-nearest neighbor, and random forest models. In external validation, LR continued to demonstrate high accuracy, sensitivity, and specificity. Although K-nearest neighbor demonstrated higher accuracy and specificity, this was offset by significantly lower sensitivity. No ML model consistently outperformed LR across evaluation criteria. CONCLUSION: Drawing data from two independent EHRs, we find LR on the basis of established risk factors demonstrated comparable performance to optimized ML algorithms. This study demonstrates that classical models built on robust, hand-chosen predictor variables may not be inferior to data-driven models for NCGC risk prediction.

Endoscopic ultrasound-guided portal pressure gradient with liver biopsy: 6 years of endo-hepatology in practice.

BACKGROUND AND AIM: The portal pressure gradient (PPG) is a useful predictor of portal hypertension (PH) related complications. We previously showed the feasibility and safety of endoscopic ultrasound guided PPG measurement (EUS-PPG). Now EUS-guided liver biopsy (EUS-bx) has been shown to be a safe and effective alternative to percutaneous or Interventional Radiology-guided liver biopsy for the diagnosis of chronic liver disease (CLD). We aimed to evaluate the correlation between PPG and clinical markers of PH, and assess the feasibility and safety of concomitant, single session EUS-PPG and EUS-bx. METHODS: This was a retrospective study of patients undergoing EUS-PPG for CLD at a single tertiary endoscopy center between February 2014 and March 2020. EUS-PPG was performed using a 25-gauge needle and compact manometer. Data analysis was performed with SAS version 9.4. RESULTS: Eighty-three patients underwent EUS-PPG with 100% technical success. The mean PPG was 7.06 mmHg (SD 6.09, range 0-27.3). PPG was higher in patients with (vs without) clinical features of cirrhosis (9.46 vs 3.61 mmHg, P < 0.0001), esophageal or gastric varices (13.88 vs 4.34 mmHg, P < 0.0001), and thrombocytopenia (9.25 vs 4.71 mmHg, P = 0.0022). In the 71 patients (85.5%) who underwent EUS-bx, 70 (98.6%) specimens were deemed adequate by the pathologist for histologic diagnosis. There were no early or late major adverse events. CONCLUSION: EUS-PPG correlates well with clinical markers of PH. EUS-bx can be performed safely during the same session as EUS-PPG, providing a comprehensive endoscopic evaluation of the patient with CLD.

Endoscopic Ultrasound-Guided Porto-systemic Pressure Gradient Measurement Correlates with Histological Hepatic Fibrosis.

BACKGROUND AND AIMS: Endoscopic ultrasound is a novel diagnostic approach to chronic liver diseases (CLDs), and EUS-guided porto-systemic pressure gradient measurement (EUS-PPG) is an important expansion with a well-developed technique. However, the clinical value and applicability of EUS-PPG measurement in predicting histologically advanced hepatic fibrosis remain unknown. METHODS: This was a single-center retrospective study on patients with various CLDs undergoing EUS-PPG and EUS-guided liver biopsy (EUS-bx) to assess if EUS-PPG measurements correlate with histological fibrosis stage and various surrogate markers for severity of CLDs and its safety. Cases with EUS-PPG were identified at the University of California Irvine, a tertiary endoscopy center, between January 2014 and March 2020. RESULTS: In 64 patients, the mean age was 57.5; 40 (62.5%), males; mean Child-Turcotte-Pugh (CTP) and Model for End-Stage Liver Disease (MELD) scores, 5.9 and 10.4, respectively. The procedure success rate was 100%. Twenty-nine (45.3%) had EUS-PPG ≥ 5 mmHg that was associated with clinical cirrhosis (p < 0.0001), clinical portal hypertension (p = 0.002), hepatic decompensation (p = 0.013), MELD-Na > 10 (p = 0.036), PLTs ≤ 120 × 109/L (p = 0.001), INR ≥ 1.05 (p = 0.007), presence of EV, GV, or PHG (p < 0.0001), biopsy-proven fibrosis stage ≥ 3 (p = 0.002), APRI > 2 (p = 0.001), and FIB-4 > 3.25 (p = 0.001). Multivariable analysis confirmed that EUS-PPG ≥ 5 mmHg was significantly associated with liver biopsy-proven fibrosis stage ≥ 3 (LR 27.0, 95% CI = 1.653-360.597, p = 0.004), independent of C-cirrhosis, C-PHTN, thrombocytopenia, splenomegaly, and APRI score > 2, and FIB-4 score > 3.25. There were no serious complications related to EUS-PPG procedures. CONCLUSIONS: EUS-PPG measurements provide excellent correlation with histological hepatic fibrosis stage and various clinical, laboratory, endoscopic and imaging variables indicative of advanced liver disease without serious adverse events.

Novel Interdisciplinary Approach to GERD: Concomitant Laparoscopic Hiatal Hernia Repair with Transoral Incisionless Fundoplication.

BACKGROUND: Transoral incisionless fundoplication (TIF) is an endoscopic alternative for the treatment of GERD. However, TIF does not address the hiatal hernia (HH). We present a novel approach with a laparoscopic HH repair followed by same-session TIF, coined concomitant transoral incisionless fundoplication (cTIF). The aim of this study was to assess the efficacy, safety, and feasibility of cTIF in a collaborative approach between Gastroenterology and surgery. STUDY DESIGN: Patients with confirmed GERD and >2 cm HH who underwent cTIF between 2018 and 2020 were included. Symptoms were assessed using the Reflux Disease Questionnaire, GERD Health-Related Quality of Life Index, and the Reflux Symptom Index pre and post cTIF. One-way ANOVA and paired samples t-test were used for statistical analysis. RESULTS: Sixty patients underwent cTIF (53% were men, mean age was 59.3 years) with 100% technical success. Mean ± SD HH measurement on endoscopy was 2.9 ± 1.5 cm. Scores on Reflux Disease Questionnaire for symptom frequency and symptom severity improved significantly from before to 6 months after cTIF (17.4 to 4.72; p < 0.01 and 16.7 to 4.56; p < 0.05, respectively). According to the GERD Health-Related Quality of Life Index, significant decreases were seen post cTIF in heartburn (23.26 to 7.37; p < 0.01) and regurgitation (14.26 to 0; p = 0.05). Reflux Symptom Index similarly decreased after cTIF (17.7 to 8.1 post cTIF; p < 0.01). Mean DeMeester score decreased from 43.7 to 4.9 and acid exposure time decreased from 12.7% to 1.28% post cTIF (p = 0.06). CONCLUSIONS: We present a novel multidisciplinary approach to GERD using a combined endoscopic and surgical approach with close collaboration between Gastroenterology and surgery. Our results suggest that cTIF is safe and effective in reducing reflux symptoms in a large spectrum of GERD patients.

Underwater versus conventional EMR for colorectal polyps: systematic review and meta-analysis.

BACKGROUND AND AIMS: Underwater EMR (UEMR) has emerged as an attractive alternative to conventional EMR (CEMR) for the resection of colorectal polyps. The purpose of this systematic review and meta-analysis was to compare UEMR and CEMR for the resection of colorectal polyps with respect to efficacy and safety. METHODS: A literature search was performed across multiple databases, including MEDLINE/PubMed, The Cochrane Library, CINAHL, Google Scholar, and Scopus, for studies that were published until May 2020. Only studies that compared the resection of colorectal polyps using UEMR with CEMR were included. Outcomes examined included rates of en bloc resection, recurrence, postprocedure bleeding, perforation, and resection time. RESULTS: Seven studies totaling 1237 polyps were included: 614 polyps were resected with UEMR and 623 polyps with CEMR. UEMR was associated with a significant increase in the rate of overall en bloc resection (odds ratio [OR], 1.84; 95% confidence interval [CI], 1.42-2.39; P < .001; I2 = 38%), with subgroup analysis showing a significant increase in the rates of en bloc resection in polyps ≥20 mm (OR, 1.51; 95% CI, 1.06-2.14; P = .02; I2 = 44%) but not in polyps <20 mm (OR, 1.07; 95% CI, .65-1.76; P = .80; I2 = 27%), and with a significant reduction in the rate of recurrence (OR, .30; 95% CI, .16-.57; P = .0002; I2 = 0%), again driven by improvements in polyps ≥20 mm. There was no significant difference in postprocedure bleeding (OR, 1.11; 95% CI, .57-2.17; P = .76; I2 = 0%) or perforation (OR, .72; 95% CI, .19-2.83; P = .64; I2 = 0%). CONCLUSIONS: The results of this systematic review and meta-analysis demonstrate that UEMR is a safe and efficacious alternative to CEMR. With appropriate training, UEMR may be strongly considered as a first-line option for resection of colorectal polyps.

Prevalence, risk factors, and surveillance patterns for gastric intestinal metaplasia among patients undergoing upper endoscopy with biopsy.

BACKGROUND AND AIMS: Gastric intestinal metaplasia (GIM) is an important precursor lesion to gastric cancer (GC), the second leading cause of cancer death worldwide. There exist few data regarding the prevalence of, risk factors for, and clinical practice patterns regarding GIM in the United States. Furthermore, there are currently no U.S. guidelines regarding screening/surveillance for GIM. METHODS: All consecutive upper endoscopic procedures from 2 academic medical centers in Seattle between 1999 and 2014 were reviewed. Demographic, clinical, and endoscopic covariates were recorded at time of endoscopy. Procedures with gastric biopsy were matched to final the histologic diagnoses, including the presence of Helicobacter pylori. Cases of GIM and dysplasia were recorded and compared with non-GIM controls using univariate and multivariable regression. Surveillance patterns for cases of GIM were recorded. RESULTS: Data from 36,799 upper endoscopies, 17,710 gastric biopsies, 2073 cases of GIM, 43 cases of dysplasia, and 78 cases of GC were captured. The point prevalence of GIM was 11.7% in patients who underwent gastric biopsy. Non-white race (P < .001), increasing age (P < .001), and presence of H pylori (P < .001) were associated with GIM. If GIM was present, increasing age (P < .001) and male gender (P < .001) were associated with progression, and the presence of H pylori (P < .001) was inversely associated with progression to dysplasia/GC. Few cases of GIM/dysplasia/GC were identified during procedures for GIM screening/surveillance. Only 16% of patients with a diagnosis of GIM received a recommendation for surveillance. CONCLUSIONS: There is a high prevalence of GIM among non-white and Hispanic Americans. Risk factors for development of GIM may be distinct from the risk factors for progression to GC.

Diagnosis and Management of Gastric Intestinal Metaplasia: Current Status and Future Directions.

Gastric intestinal metaplasia (GIM) is a known premalignant condition of the human stomach along the pathway to gastric cancer (GC). Histologically, GIM represents the replacement of normal gastric mucosa by mucin-secreting intestinal mucosa. Helicobacter pylori infection is the most common etiologic agent of GIM development worldwide. The prevalence of GIM is heterogeneous among different regions of the world and correlates with the population endemicity of H. pylori carriage, among other environmental factors. GC remains the third leading cause of cancer-related mortality globally. GIM is usually diagnosed by upper endoscopy with biopsy, and histologic scoring systems have been developed to risk-stratify patients at highest risk for progression to GC. Several recent endoscopic imaging modalities may improve the optical detection of GIM and early GC. Appropriate surveillance of GIM may be cost effective and represents an opportunity for the early diagnosis and therapy of GC. Certain East Asian nations have established population-level programs for the screening and surveillance of GIM; guidelines regarding GIM surveillance have also recently been published in Europe. By contrast, few data exist regarding the appropriateness of surveillance of GIM in the United States. In this review, we discuss the pathogenesis, epidemiology, diagnosis, and management of GIM with an emphasis on the role of appropriate endoscopic surveillance.

Low Frequency of Lymph Node Metastases in Patients in the United States With Early-stage Gastric Cancers That Fulfill Japanese Endoscopic Resection Criteria.

BACKGROUND & AIMS: In the West, early gastric cancer is increasingly managed with endoscopic resection (ER). This is, however, based on the assumption that the low prevalence and risk of lymph node metastases observed in Asian patients is applicable to patients in the United States. We sought to evaluate the frequency of and factors associated with metastasis of early gastric cancers to lymph nodes, and whether the Japanese ER criteria are applicable to patients in the US. METHODS: We performed a retrospective study of 176 patients (mean age 68.5 years; 59.1% male; 58.5% white) who underwent surgical resection with lymph node dissection of T1 and Tis gastric adenocarcinomas, staged by pathologists, at 7 tertiary care centers in the US from January 1, 1999, through December 31, 2016. The frequency of lymph node metastases and associated risk factors were determined. RESULTS: The mean size of gastric adenocarcinomas was 23.0 ± 16.6 mm-most were located in the lower-third of the stomach (67.0%), invading the submucosa (55.1%), and moderately differentiated (31.3%). Lymphovascular invasion was observed in 18.2% of lesions. Overall, 20.5% of patients had lymph node metastases. Submucosal invasion (odds ratio, 3.9; 95% CI, 1.4-10.7) and lymphovascular invasion (odds ratio, 4.6; 95% CI, 1.8-12.0) were independently associated with increased risk of metastasis to lymph nodes. The frequency of lymph node metastases among patients fulfilling standard and expanded Japanese criteria for ER were 0 and 7.5%, respectively. CONCLUSIONS: The frequency of lymph node metastases among patients with early gastric cancer in a US population is higher than that of published Asian series. However, early gastric cancer lesions that meet the Japanese standard criteria for ER are associated with negligible risk of metastasis to lymph nodes, so ER can be recommended for definitive therapy. Expanded criteria cancers appear to have a higher risk of metastasis to lymph nodes, so ER may be considered for select cases.

Searching for Bacterial Biofilm in Recurrent Cholangitis in Primary Sclerosing Cholangitis: A Case Presentation and Introduction of an Unexplored Disease Mechanism.

Inflammation and fibrosis of the bile ducts are the defining pathological characteristics of primary sclerosing cholangitis (PSC). A previously unexplored mechanism for recurrent cholangitis, one of PSC's most common presentations, is bacterial colonization of the biliary epithelium in the form of biofilm, which may confer resistance to antibiotics and host phagocytic machinery. The aim of the current study was to assess whether bacteria could be seen on the liver explant and whether they organized in the form of biofilm. An explanted PSC liver from a 60-year-old male who suffered from recurrent cholangitis was formalin-fixed, paraffin-embedded and Gram stained. The specimens were observed under light microscopy. Neither bacteria nor biofilm were detected. We did not detect bacteria or biofilm in the liver explant of a single PSC patient with recurrent cholangitis using standard light microscopy. We suspect this may be in part due to techniques related to tissue preservation and microscopy.

Association of gastric intestinal metaplasia and East Asian ethnicity with the risk of gastric adenocarcinoma in a U.S. population.

BACKGROUND AND AIMS: Although the incidence of gastric cancer is higher than that of esophageal cancer in the United States, no screening or surveillance guidelines exist. The aim of this study is to evaluate the association between gastric intestinal metaplasia and the risk of gastric cancer in a U.S. tertiary care system with a large immigrant population. METHODS: This is a retrospective case-control study with cases of biopsy-proven gastric cancer matched (by age and gender) to controls without gastric cancer who had undergone EGD. The presence of gastric intestinal metaplasia was ascertained from pathology reports. Other potential risk factors for gastric cancer were abstracted from medical records as follows: country of origin, Helicobacter pylori infection, family history of gastric cancer, alcohol consumption, smoking, and history of partial gastrectomy (Billroth I or II). Conditional logistic regression was used to identify independent risk factors for gastric cancer. RESULTS: One hundred fifty-two cases of gastric cancer were compared with 456 age- and gender-matched controls. The mean age was 66 years, and 57% were male. Multivariable analysis identified 2 significant predictors of gastric cancer: the presence of gastric intestinal metaplasia (odds ratio [OR], 9.3; 95% confidence interval [CI], 4.5-18.9; P < .001) and East Asian ethnicity (OR, 15.9; 95% CI, 5.8-43.6; P < .001). CONCLUSION: The presence of gastric intestinal metaplasia on endoscopy and East Asian ethnicity were significant risk factors for gastric cancer. Screening East Asian immigrants and surveying patients with gastric intestinal metaplasia may improve the rates of early detection of gastric cancer in the United States.