The incremental yield of adenoma detection with I-Scan versus high-definition white light colonoscopy-a systematic review and meta-analysis of randomized studies.

INTRODUCTION: The incremental yield of I-Scan virtual chromoendoscopy compared to high-definition white light endoscopy (HD-WLE) in detection of colorectal adenomas has not been thoroughly elucidated. METHODS: A systematic search from inception to April 2023 was conducted to identify randomized controlled trials (RCTs) comparing I-Scan to HD-WLE for detection of adenomas. A random effects model was used to compute risk difference (RD) with corresponding 95% confidence intervals in adenoma detection rate (ADR). Influence analysis was done to assess robustness of findings. The number needed to diagnose was computed. Heterogeneity was assessed using the I2 statistic and explored further by subgroup analyses defined a priori. Certainty in effect estimates was assessed using the GRADE approach. RESULTS: We identified four studies (I-Scan n = 730, HD-WLE n = 765). I-Scan increased adenoma detection by 9% (risk difference (RD), 0.09; 0.04, 0.14; I2 02%; certainty, low). Influence analysis revealed that the gain in yield remained statistically significant with exclusion of all but one study. The number needed to capture one additional adenomatous polyp with I-Scan use was 11.2. I-Scan 1 use was associated with a statistically significant gain in ADR, whereas no significant difference in ADR was noted with I-Scan use on subgroup analysis. DISCUSSION: In conclusion, I-Scan increases the yield of adenoma detection by 9% compared to HD-WLE, with low certainty in the estimate of this effect. Data on the gain in yield of detecting large polyps, sessile serrated lesions, and on the impact of formally training endoscopists and trainees in I-Scan use and similar technology on adenoma detection rate are needed.

Diet and carcinogenesis of gastric cancer.

PURPOSE OF REVIEW: Several recent studies have corroborated a strong association between diet and gastric cancer risk; investigators have also identified dietary factors that protect against gastric cancer. This review summarizes the literature on this topic and guides future research directions. RECENT FINDINGS: High-salt intake disrupts the gastric mucosal defense barrier, promoting Helicobacter pylori colonization and penetration of other carcinogenic compounds. Processed foods, processed meats, red meat, alcohol, foods with high dietary fat, and dietary cholesterol increase the risk of gastric carcinogenesis. On the other hand, increased consumption of fruits, vegetables, whole grains, nuts, and a low-salt diet may offer a protective effect. SUMMARY: Despite decreases in gastric cancer incidence because of increased identification and treatment of H. pylori , gastric cancer remains one of the most common cancers worldwide with a high mortality rate. This disturbing statistic highlights the importance of reducing and eliminating other risk factors for gastric cancer. There is a strong body of evidence that alcohol, processed foods, high salt intake, high fat intake, and foods with animal products (meats, eggs, and dairy) increase the risk of gastric cancer. A diet that is high in whole grains, fruits, vegetables, nuts and is low in salt may reduce the risk of gastric cancer.

Outcomes of Radiofrequency Ablation Compared to Liquid Nitrogen Spray Cryotherapy for the Eradication of Dysplasia in Barrett's Esophagus.

INTRODUCTION: Current guidelines recommend endoscopic eradication therapy (EET) for Barrett's esophagus (BE) with dysplasia and intramucosal adenocarcinoma using either radiofrequency ablation (RFA) or liquid nitrogen spray cryotherapy (LNSC). The aims of this multicenter study are to compare the rate and number of treatment sessions of RFA vs. LNSC to achieve CE-D and CE-IM and assess outcomes for those who switched therapy. METHODS: This is a retrospective cohort study of patients with BE undergoing EET. Demographics, baseline variables, endoscopy details, and histology information were abstracted. RESULTS: One hundred and sixty-two patients were included in this study with 100 patients in the RFA group and 62 patients in the LNSC group. The rate of CE-D and CE-IM did not differ between the RFA group and LNSC group (81% vs. 71.0%, p = 0.14) and (64% vs. 66%, p = 0.78), respectively. The number of sessions to achieve CE-D and CE-IM was higher with LNSC compared to RFA (4.2 vs. 3.2, p = 0.05) and (4.8 vs. 3.5, p = 0.04), respectively. The likelihood of developing recurrent dysplasia was higher among patients who did not achieve CE-IM (12%) compared to those who did achieve CE-IM (4%), p = 0.04. Similar findings were found in those who switched treatment modalities. DISCUSSION: EET is highly effective in eradication of Barrett's associated dysplasia and neoplasia. Both RFA and LNSC achieved similar rates of CE-D and CE-IM although LNSC required more sessions. Also, achievement of CE-IM was associated with less recurrence rates of dysplasia.

"Wet Heparin" and "Wet Saline" EUS-Guided Liver Biopsy Techniques Both Provide High Rates of Specimen Adequacy for Benign Parenchymal Liver Disease.

BACKGROUND: Endoscopic ultrasound-guided liver biopsy (EUS-LB) has emerged as a viable mean to obtain core tissue, but the optimal tools and techniques are still an area of active investigation. AIMS: (1) To compare tissue adequacy using "wet saline" (WS) vs. "wet heparin" (WH) technique (2) To compare post-procedure pain between EUS-LB and percutaneous liver biopsy (PLB). METHODS: Retrospective review of consecutive patients who underwent EUS-LB and PLB for benign parenchymal liver disease between May 2017 to October 2019 at a single tertiary veterans affairs medical center. RESULTS: About 257 biopsies from 217 patients were included. Among the 102 EUS-LB specimens, 53 were obtained using WS technique and 49 were obtained using WH technique. Specimen adequacy was similar in both groups. Median Aggregate Specimen Length (ASL) and length of longest piece did not differ significantly between WS and WH groups. Clots were present more frequently in the WS group. Among patients who underwent EUS-LB of both right and left liver lobes, an adequate biopsy was obtained in 85% of patients in the WS group and 96% of patients in the WH group. The percentage of patients experiencing immediate post-procedure pain was higher with PLB compared to EUS-LB, but these results were not statistically significant. CONCLUSIONS: Both WS and WH EUS-LB techniques can offer high rates of specimen adequacy with low rates of pain and other post-procedure complications.

Correlation of Probe-Based Confocal Laser Endomicroscopy (pCLE) and Mucosal Integrity Testing (MIT) with Epithelial Barrier Function and Presence of Gastroesophageal Reflux Disease (GERD).

INTRODUCTION: Epithelial barrier function (EBF) disruption is a key mechanism underlying gastroesophageal reflux disease (GERD). Our aim was to assess whether two novel technologies, probe-based confocal laser endomicroscopy (pCLE) and mucosal integrity testing (MIT), could assess EBF. METHODS: We prospectively enrolled patients undergoing upper endoscopy for refractory GERD or non-GERD conditions. Patients underwent esophagogastroduodenoscopy, pCLE, MIT, esophageal biopsy at 2 cm and 6 cm above the esophagogastric junction, and wireless pH testing. To assess EBF in vitro, biopsies were mounted in a mini-Ussing chamber, 1 ml of fluorescein was instilled on the mucosal side, and concentration of fluorescein on the serosal side was measured at 3 h. RESULTS: We enrolled 54 subjects (28 GERD, 26 non-GERD based on Lyon consensus criteria). In vivo permeability assessed by pCLE did not differ significantly between GERD vs. non-GERD patients and did not correlate with in vitro permeability. Mean MIT at 2 cm was lower in GERD compared to non-GERD (1914 vs. 3727 ohms). MIT correlated inversely with in vitro permeability at 2 cm and at 6 cm. Using a predictive model that used slope and intercept of MIT at 2 cm and 6 cm, sensitivity and specificity of MIT at identifying GERD was 76% and 72%, respectively. CONCLUSION: pCLE did not differentiate GERD vs non-GERD and did not correlate with EBF measured in vitro. MIT, on the other hand, may be more promising as it differentiated GERD vs non-GERD and correlated with EBF measured in vitro.

Endoscopic resection reduces morbidity when compared to surgery in veterans with large and complex colorectal polyps.

INTRODUCTION: Data supporting endoscopic resection (ER) over surgical resection (SR) for large and complex polyps come from high-volume centers. The aim of this study was to determine whether these favorable outcomes can be replicated among endoscopists at tertiary Veterans Affairs Medical Centers (VAMCs) who perform 25 to 30 ER cases a year. METHODS: Patients with adenomatous polyps or intra-mucosal cancers ≥ 2 cm in size who underwent ER or SR were identified from prospectively maintained databases at the 2 tertiary VAMCs in Veterans Integrated Service Network 6 (VISN6). The primary outcome was the rate of serious complications in the ER and SR groups. RESULTS: 310 ER and 81 SR patients met the inclusion criteria. ER was successful in 97% of all polyps, and 93% of polyps ≥ 4 cm. The rate of serious complications was significantly lower with ER compared to SR (0.6% vs. 22%, p = 0.00001). These findings persisted even after limiting the analysis to polyps ≥ 4 cm and after propensity score matching. If all ER patients had instead undergone laparoscopic surgery, the estimated risk of a serious complication was still higher than ER for all patients (8% vs. 0.6%, p < 0.0001) but not significantly higher for polyps ≥ 4 cm (8% vs 2%, p = 0.17). CONCLUSIONS: This study documents high success rates for ER in veterans with colorectal polyps ≥ 2 cm and ≥ 4 cm. When compared to a historical cohort of surgical patients, a strategy of attempting ER first reduced morbidity. A randomized trial is warranted to compare ER to laparoscopic surgery for polyps ≥ 4 cm.

Surgery Reduces Risk of Complications Even in High-Risk Veterans After Endoscopic Therapy for Biliary Stone Disease.

BACKGROUND: In otherwise healthy patients, randomized trials have shown reduced mortality with cholecystectomy (CCY) when compared to non-operative management after endoscopic retrograde cholangiopancreatography (ERCP) for biliary stone disease. These findings may not apply to veterans with multiple comorbidities, who have an increased risk of postoperative complications. AIMS: Our study assessed the benefit of CCY among veterans with multiple comorbidities. METHODS: Medical records of patients undergoing ERCP for biliary stone-related diseases from July 2008 to December 2016 were reviewed. Among patients who did not undergo CCY, risk of postoperative complications or death with CCY was estimated using the American College of Surgeons National Surgery Quality Improvement Program risk calculator. Charlson comorbidity index (CCI) and American Society of Anesthesiologists classification system (ASA) were used to assess patient's functional status. The primary outcome was incidence of recurrent biliary events or death with non-operative management, compared to estimated risk of serious postoperative complications or death with CCY. RESULTS: A total of 152 patients met inclusion criteria, 81 of whom did not undergo CCY. Patients managed non-operatively were older and less medically fit than patients who underwent CCY. Biliary complications recurred in 23 patients managed non-operatively, including 3 deaths due to cholangitis. Among patients with CCI ≥ 3 and ASA ≥ 3 who were managed non-operatively (n = 43), the risk of serious biliary events was significantly higher than estimated risk of serious postoperative complications with laparoscopic CCY (26 vs 5%, p < 0.001). CONCLUSION: Our study suggests that non-operative management is associated with a higher risk of complications than laparoscopic CCY, even among veterans with significant comorbidities.

Lifestyle Medicine for the Prevention and Treatment of Pancreatitis and Pancreatic Cancer.

The incidence of pancreatitis and pancreatic cancer is on the upswing in the USA. These conditions often lead to higher healthcare costs due to the complex nature of diagnosis and the need for specialized medical interventions, surgical procedures, and prolonged medical management. The economic ramification encompasses direct healthcare expenses and indirect costs related to productivity losses, disability, and potential long-term care requirements. Increasing evidence underscores the importance of a healthy lifestyle in preventing and managing these conditions. Lifestyle medicine employs evidence-based interventions to promote health through six key pillars: embracing a whole-food, plant-predominant dietary pattern; regular physical activity; ensuring restorative sleep; managing stress effectively; removing harmful substances; and fostering positive social connections. This review provides a comprehensive overview of lifestyle interventions for managing and preventing the development of pancreatitis and pancreatic cancer.

Endoscopic retrograde cholangiopancreatography-related early perforations: A study of effects of procedure duration, complexity, and endoscopist experience.

BACKGROUND: Perforations (Perf) during endoscopic retrograde cholangiopancreatography (ERCP) are rare (< 1%) but potentially fatal events (up to 20% mortality). Given its rarity, most data is through case series studies from centers or analysis of large databases. Although a meta-analysis has shown fewer adverse events as a composite (bleeding, pancreatitis, Perf) during ERCP performed at high-volume centers, there is very little real-world data on endoscopist and center procedural volumes, ERCP duration and complexity on the occurrence of Perf. AIM: To study the profile of Perf related to ERCP by center and endoscopist procedure volume, ERCP time, and complexity from a national endoscopic repository. METHODS: Patients from clinical outcomes research initiative-national endoscopic database (2000-2012) who underwent ERCP were stratified based on the endoscopist and center volume (quartiles), and total procedure duration and complexity grade of the ERCP based on procedure details. The effects of these variables on the Perf that occurred were studied. Continuous variables were compared between Perf and no perforations (NoPerf) using the Mann-Whitney U test as the data demonstrated significant skewness and kurtosis. RESULTS: A total of 14153 ERCPs were performed by 258 endoscopists, with 20 reported Perf (0.14%) among 16 endoscopists. Mean patient age in years 61.6 ± 14.8 vs 58.1 ± 18.8 (Perf vs. NoPerf, P = NS). The cannulation rate was 100% and 91.5% for Perf and NoPerf groups, respectively. 13/20 (65%) of endoscopists were high-volume performers in the 4th quartile, and 11/20 (55%) of Perf occurred in centers with the highest volumes (4th quartile). Total procedure duration in minutes was 60.1 ± 29.9 vs 40.33 ± 23.5 (Perf vs NoPerf, P < 0.001). Fluoroscopy duration in minutes was 3.3 ± 2.3 vs 3.3 ± 2.6 (Perf vs NoPerf P = NS). 50% of the procedures were complex and greater than grade 1 difficulty. 3/20 (15%) patients had prior biliary surgery. 13/20 (65%) had sphincterotomies performed with stent insertion. Peritonitis occurred in only 1/20 (0.5%). CONCLUSION: Overall adverse events as a composite during ERCP are known to occur at a lower rate with higher volume endoscopists and centers. However, Perf studied from the national database show prolonged and more complex procedures performed by high-volume endoscopists at high-volume centers contribute to Perf.

Co-existing inflammatory bowel disease and Barrett's esophagus is associated with esophageal dysplasia: a propensity score-matched cohort.

Background and study aims Barrett's esophagus (BE) and inflammatory bowel disease (IBD) predispose to the development of dysplasia and cancer. It is unclear if the inflammatory cascade seen in IBD affects disease progression in BE. We aimed to determine if patients with BE who have co-existing IBD had a higher risk of dysplasia, nodular disease, or longer segments than BE patients without IBD. Patients and methods This was a multicenter, retrospective propensity score-matched cohort study. We compared rates of dysplasia, nodular disease, and segment length in patients with BE and IBD (cases) to patients with BE who did not have IBD (controls). Controls were 1:1 propensity score matched with controls for age, sex, body mass index (BMI), smoking, and hiatal hernia. Results A total of 132 patients were included in the IBD + BE group and 132 patients in the BE group. Patients with IBD + BE had higher rates of esophageal dysplasia compared to controls (15.9 % vs. 6.1 % [adjusted odds ratio [OR]: 2.9, 95 % CI: 1.2-6.9]) and more nodules (9.8 % vs. 3.0 % [adjusted OR: 3.5, 95 % CI: 1.1-11.0]). IBD + BE group was also associated with longer BE segments (43.9 % vs. 12.1 % [OR: 5.7, 95 % CI: 3.0-10.6]). Conclusions Co-existing IBD may increase the risk of dysplasia and esophageal nodules in patients with BE. Our findings may have implications for BE surveillance intervals in IBD patients. Prospective studies are needed to confirm our findings.

Deep learning systems detect dysplasia with human-like accuracy using histopathology and probe-based confocal laser endomicroscopy.

Probe-based confocal laser endomicroscopy (pCLE) allows for real-time diagnosis of dysplasia and cancer in Barrett's esophagus (BE) but is limited by low sensitivity. Even the gold standard of histopathology is hindered by poor agreement between pathologists. We deployed deep-learning-based image and video analysis in order to improve diagnostic accuracy of pCLE videos and biopsy images. Blinded experts categorized biopsies and pCLE videos as squamous, non-dysplastic BE, or dysplasia/cancer, and deep learning models were trained to classify the data into these three categories. Biopsy classification was conducted using two distinct approaches-a patch-level model and a whole-slide-image-level model. Gradient-weighted class activation maps (Grad-CAMs) were extracted from pCLE and biopsy models in order to determine tissue structures deemed relevant by the models. 1970 pCLE videos, 897,931 biopsy patches, and 387 whole-slide images were used to train, test, and validate the models. In pCLE analysis, models achieved a high sensitivity for dysplasia (71%) and an overall accuracy of 90% for all classes. For biopsies at the patch level, the model achieved a sensitivity of 72% for dysplasia and an overall accuracy of 90%. The whole-slide-image-level model achieved a sensitivity of 90% for dysplasia and 94% overall accuracy. Grad-CAMs for all models showed activation in medically relevant tissue regions. Our deep learning models achieved high diagnostic accuracy for both pCLE-based and histopathologic diagnosis of esophageal dysplasia and its precursors, similar to human accuracy in prior studies. These machine learning approaches may improve accuracy and efficiency of current screening protocols.

Semi-Supervised Classification of Noisy, Gigapixel Histology Images.

One of the greatest obstacles in the adoption of deep neural networks for new medical applications is that training these models typically require a large amount of manually labeled training samples. In this body of work, we investigate the semi-supervised scenario where one has access to large amounts of unlabeled data and only a few labeled samples. We study the performance of MixMatch and FixMatch-two popular semi-supervised learning methods-on a histology dataset. More specifically, we study these models' impact under a highly noisy and imbalanced setting. The findings here motivate the development of semi-supervised methods to ameliorate problems commonly encountered in medical data applications.

Neoadjuvant cryotherapy improves dysphagia and may impact remission rates in advanced esophageal cancer.

Background and study aims Liquid nitrogen spray cryotherapy (LNSC) can provide rapid dysphagia relief, and is postulated to stimulate a local antitumor immune response. The aim of this prospective pilot clinical trial was to evaluate the safety and efficacy of LNSC when administered prior to chemoradiotherapy. Patients and methods Treatment-naïve adult patients with dysphagia at the time of biopsy-proven squamous carcinoma or adenocarcinoma of the esophagus were prospectively enrolled at two tertiary medical centers. Patients underwent a single session of LNSC. The primary outcome measure was change in dysphagia at 1 and 2 weeks post-cryotherapy. A secondary outcome measure was clinical complete response rate (CR) following chemoradiotherapy. Results Twenty-five patients were screened, of whom 21 patients were eligible and enrolled. There were seven with metastatic and 14 with locally advanced cancer. The primary outcome of dysphagia improvement of ≥ 1 point occurred in 15/21 patients (71 %) at 1 week, and 10/20 patients (50 %) at 2 weeks. The median dysphagia score improved by 1 at 1 week ( P  = 0.0003), and 0.5 at 2 weeks ( P  = 0.02). Six of nine patients (67 %) with locally advanced cancer who completed chemoradiation did not have residual tumor cells on mucosal biopsy, and five of nine patients (56 %) had a clinical CR. There were no serious cryotherapy-related complications. Conclusions LNSC provided safe and effective palliation for esophageal cancer patients who presented with dysphagia at index diagnosis. Its combination with chemoradiotherapy did not lead to any serious toxicity. Our study provides a scientific rationale for pursuing larger clinical trials addressing synergistic effects of combining LNSC with chemoradiation.

Accuracy of probe-based confocal laser endomicroscopy (pCLE) compared to random biopsies during endoscopic surveillance of Barrett's esophagus.

BACKGROUND: For surveillance of Barrett's esophagus (BE), the current standard of random 4-quadrant biopsies misses 10 - 50 % of esophageal neoplasms, and does not permit real-time decision-making. Probe-based confocal laser endomicroscopy (pCLE) permits real-time in vivo histologic assessment of esophageal mucosa during upper endoscopy. Prospective studies comparing the accuracy of pCLE to 4-quadrant biopsies in routine clinical practice are lacking. METHODS: Consecutive patients with BE underwent high definition white light and narrow-band imaging followed by pCLE and targeted biopsy or mucosal resection. Four-quadrant biopsies were obtained during the same session. Baseline variables, real-time pCLE interpretation, and histology results were prospectively recorded. Blinded expert review of pCLE sequences and histology specimens was performed. A sample size of 64 patients was calculated a priori based on 3 % estimated prevalence of high grade dysplasia (HGD) or cancer. RESULTS: In total, 66 patients were included in the study. The prevalence of HGD or cancer was 4.55 %. Both real-time and blinded pCLE correctly identified all cases of cancer. For the primary outcome, real-time pCLE was 98 % specific but only 67 % sensitive for HGD/cancer compared to non-blinded pathologist interpretation. For HGD and cancer, inter-observer agreement was substantial between real-time and blinded endomicroscopists (kappa = 0.6). pCLE identified dysplasia in 75 % of cases where both blinded and unblinded pathology interpretation was low grade dysplasia. CONCLUSIONS: pCLE demonstrates high specificity for detecting dysplasia and cancer, but lower sensitivity may limit its utility in routine BE surveillance. pCLE may have a role in confirming LGD in real-time before eradication therapy.