Potential clinical complications of Orise™ gel use, a new submucosal lifting agent: experience from a tertiary care center and review of the literature.

Background: Endoscopic mucosal resection (EMR) involves forming a fluid cushion in the submucosal area with a lifting agent, followed by superficial resection. Orise™ gel is one of the commonly used lifting agents for EMR. We present a case series and literature review that analyzes the characteristic histopathological findings and clinical implications observed where Orise™ gel was used before EMR. Methods: Colon resection specimens and prior EMR specimens where Orise™ gel was used were reviewed for patients undergoing EMR between January 2018 and December 2020. The literature review included relevant studies from the Medline and Cochrane databases from January 2018 to December 2020. Results: A total of 12 colon polyp EMRs using Orise gel were performed during the study period. Seven patients (58.34%) underwent surgical resection. Histological examination revealed that, after the EMR procedure, the Orise™ gel material changed its morphological characteristics over time from a basophilic (bluish) non-inflamed pattern to an eosinophilic (pink) type pattern, eliciting a foreign body reaction. The endoscopic appearance and examination of the excised specimens weeks after injection gave the impression of a mass in some cases. The material was also present transmurally and in some cases in the peri-intestinal adipose tissue. Conclusions: It was observed that Orise™ gel use elicits a foreign body-type granulomatous reaction. This potential side effect may lead to overdiagnosis of a mass/lesion and unnecessary surgical interventions. This case series and review of the literature aims to increase awareness of the changes caused by Orise™ gel in the gastrointestinal tract.

Ustekinumab does not increase risk of new or recurrent cancer in inflammatory bowel disease patients with prior malignancy.

BACKGROUND AND AIM: There is limited data on the rate of new or recurrent cancer in patients with inflammatory bowel disease (IBD) and a history of prior or current malignancy who are initiated on biologic therapies. Furthermore, there is no data on this topic in patients using ustekinumab. METHODS: The retrospective study included 341 patients with IBD and a history of cancer who were subsequently treated with vedolizumab (VDZ; n = 34), ustekinumab (USK; n = 27), tumor necrosis factor α antagonists (anti-TNF; n = 99), or had no immunosuppressive therapy (control; n = 181). Cox proportional hazard models were developed to determine the independent effect of post-cancer immunosuppressive treatment on the occurrence of incident cancer. RESULTS: Over a median of 5.2 person-years of follow up, cancer recurrence occurred in only one patient on anti-TNF, while new cancers developed in one patient on VDZ, three patients on USK, and six patients on anti-TNF, corresponding to cancer rates of 0.4, 1.8, and 0.7 per 100 person-years, respectively. The rate of incident cancer in control patients was 2.4 per 100 person-years and included 18 new and 9 recurrent cancers. Compared with controls, a stepwise Cox proportional hazards model adjusting for significant covariates found no increased risk of incident cancer in patients receiving post-malignancy treatment with USK (hazard ratio [HR] 0.88; 95% confidence interval [CI] 0.25-3.03), VDZ (HR 0.18; 95% CI 0.03-1.35), or anti-TNF (HR 0.47; 95% CI 0.20-1.12). CONCLUSION: Use of biologic therapy in IBD patients with a previous history of malignancy was not associated with an increased risk of new or recurrent cancer.

From hepatitis A to E: A critical review of viral hepatitis.

Viral infections affecting the liver have had an important impact on humanity, as they have led to significant morbidity and mortality in patients with acute and chronic infections. Once an unknown etiology, the discovery of the viral agents triggered interest of the scientific community to establish the pathogenesis and diagnostic modalities to identify the affected population. With the rapid scientific and technological advances in the last centuries, controlling and even curing the infections became a possibility, with a large focus on preventive medicine through vaccination. Hence, a comprehensive understanding of hepatitis A, B, C, D and E is required by primary care physicians and gastroenterologists to provide care to these patients. The review article describes the epidemiology, pathogenesis, clinical presentation, diagnostic tools and current medication regimens, with a focus on upcoming treatment options and the role of liver transplantation.

Pathogenetic mechanisms of nonalcoholic fatty liver disease and inhibition of the inflammasome as a new therapeutic target.

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide, and its incidence is increasing. Nonalcoholic steatohepatitis (NASH), the progressive form of the disease, can lead to end-stage liver disease. The pathogenesis of the disease is not fully understood, and there is currently no specific treatment. Therefore, an effective and reliable treatment modality is needed. In recent years, the inflammasome has been shown to play a vital role in many stages of NAFLD pathogenesis. In particular, the detection, by toll-like receptors, of pathogen-associated molecular patterns induced by the gut-liver axis triggers the formation of the NLRP3 (NLR family pyrin domain-containing protein 3) inflammasome. Stimulation of damage-associated molecular patterns also activates the NLRP3 inflammasome. The activated inflammasome has caspase-1 activity, which leads to the release of interleukin (IL)-1 and IL-18 and formation of pores in the cell wall. This process spreads the inflammatory process to the outside of the cell and induces inflammatory cell death (pyroptosis). Subsequent progression of the inflammatory process leads to fibrosis. Recent evidence suggests that the NLRP3 inflammasome may be a potential target for the treatment of NASH. The discovery of specific NLRP3 inflammasome blockers in recent years and evidence of their positive effects in experimental models support this therapeutic approach. In this article, we discuss recent evidence on the pathogenesis of NAFLD, the role of the inflammasome in the pathogenesis of NAFLD, and the potential effects of inhibition of the inflammasome.

Early Detection of Hepatocellular Carcinoma Recurrence in the Posttransplant Population: A Comparison of RETREAT and Cleveland Clinic Florida Scoring System.

BACKGROUND: Liver transplantation (LT) for hepatocellular carcinoma (HCC) is curative in most cases; however, recurrence is observed in some patients. The Risk Estimation of Tumor Recurrence After Transplant (RETREAT) score is an externally validated scoring system for prediction of post-LT HCC recurrence. The Cleveland Clinic Florida Scoring System (CCFSS) is a potential new scoring system for prediction of HCC recurrence. Our study aimed to compare the RETREAT and CCFSS. METHODS: We conducted a retrospective cohort study of 52 adult patients with HCC who underwent LT at a tertiary care center. Mantel-Haenszel chi-square analyses were conducted to compare the RETREAT and CCFSS classifications for detecting HCC recurrence. RESULTS: A total of 52 patients underwent LT. The median follow-up period was 37 months. Four patients had post-LT HCC recurrence, with all recurrences occurring within 2 years of LT. The RETREAT score was better able to detect low, moderate, and high levels of risk (P < .001), compared to the CCFSS score (P = 0.480). Both risk scores had a sensitivity of 75%; the specificity of the RETREAT score was 95.8%, whereas the specificity of the CCFSS was 60.4%. Alpha-fetoprotein level at the time of LT was associated with HCC recurrence (P = .014). CONCLUSIONS: This is the first study to evaluate the CCFSS as a potential new scoring system to predict HCC recurrence after LT. The RETREAT score is more specific than the CCFSS. The incorporation of alpha-fetoprotein level at the time of LT improves the estimation of HCC recurrence in the post-LT period.

Association of Complicated Diverticulitis With Development of De Novo Inflammatory Bowel Disease.

BACKGROUND: There has been a historic similarity in the epidemiology and pathophysiology of diverticular disease and inflammatory bowel disease (IBD). Because there are limited to no data on the role of diverticulitis as a potential risk factor for de novo IBD, we aimed to evaluate the role of diverticulitis and complicated diverticulitis as a potential predictor of IBD. METHODS: We performed a retrospective, single-center study including patients older than age 18 years who were diagnosed with diverticulitis from January 2012 until December 2018 without a prior diagnosis of IBD. These patients were then evaluated for development of IBD. Univariate and multivariate analyses were conducted to compare the characteristics and outcomes between patients who did or did not develop IBD. RESULTS: A total of 2770 patients were diagnosed with diverticulitis from 2012 until 2018. Of these patients, 17 were diagnosed with IBD, resulting in an incidence rate of 0.23% per patient-year. The incidence rate among patients who required surgery for diverticulitis was 0.44% per patient-year, and patients with complicated diverticulitis had an incidence rate of 0.91% per patient-year. Univariate analysis showed that the need for surgery related to diverticulitis (hazard ratio [HR], 6.27; P = 0.003) and complicated diverticulitis was associated with the development of IBD (HR, 14.71; P < 0.001). Multivariate analysis showed that complicated diverticulitis was the sole factor associated with IBD (HR, 10.34; P < 0.001). CONCLUSIONS: Patients with diverticulitis are at a higher risk of developing de novo IBD. This risk is highest in patients with complicated diverticulitis.

Utility and safety of balloon-assisted enteroscopy in patients with left ventricular assist devices: a retrospective multicenter study.

Objective and study aims Patients with left-ventricular assist devices (LVADs) have an increased risk of gastrointestinal bleeding, especially from the small bowel, often necessitating evaluation with balloon-assisted enteroscopy (BAE). Our study aimed to assess the periprocedural safety and utility of BAE for gastrointestinal bleeding in patients with LVADs. Patients and methods This was a multicenter retrospective cohort study of adults with LVADs who underwent BAE between January 2007 to December 2018. Results Thirty-four patients underwent a total of 46 BAEs (9 were single-balloon enteroscopies [SBEs] and 37 were double-balloon enteroscopies [DBEs]). Mean age of patients was 66.4 ±â€Š8.3 years. Patients tolerated anesthesia well, without complications. There were no complications from the BAE itself. One patient required repeat BAE due to a progressive drop in hemoglobin and another patient developed paroxysmal supraventricular tachycardia. One patient died within 72 hours of the procedure due to worsening of LVAD thrombosis. Diagnostic yields were 69.6 % for all procedures, 73.0 % for DBE and 55.6 % for SBE ( P  = 0.309). Therapeutic yields were 67.4 % overall: 73.0 % for DBE and 44.4 % for SBE ( P  = 0.102). In those that presented with overt gastrointestinal bleeding, DBE had a higher diagnostic yield compared to SBE (84.2 % vs. 42.9 %; P  = 0.057) and a significantly higher therapeutic yield (84.2 % vs. 28.6 %; p = 0.014). Conclusions This is the largest multicenter study of patients with LVADs who underwent DBE. BAE appears to be a safe and useful modality for the evaluation of gastrointestinal bleeding in these patients.

Afro-Caribbeans Have a Lower Prevalence of Advanced Colon Neoplasia than African-Americans.

BACKGROUND/AIMS: The black population in the USA is a heterogeneous group composed of smaller subgroups from different origins. The definition of black in many colorectal cancer (CRC) risk studies is vague, and differences in CRC risk comparing black subpopulations have not been evaluated. The aim of the study is to compare advanced colorectal neoplasia (ACN) between two subgroups of black populations: African-American (AA) and Afro-Caribbean (AC). A secondary aim was to determine whether there are differences in prevalence of adenomas. METHODS: This was a retrospective study of 3797 AA and AC patients undergoing first time screening colonoscopy in two different institutions in the USA. RESULTS: Overall adenoma prevalence was 29.3% for the entire population with 29.5% in AAs and 29.0% in AC with no statistically significant difference between the study groups (AOR: 1.02; 95% CI 0.88-1.18, P = 0.751). However, ACN was significantly higher in the AA group (11.8%) compared to AC (9.0%) (AOR: 1.30, 95% CI 1.02-1.66, P = 0.034). It was observed that AAs had ACN at a higher BMI than AC. After adjusting for BMI/ethnicity interactions, the difference in ACN between both groups became more significant (AOR: 1.93, 95% CI 1.16-3.23, P = 0.012). CONCLUSIONS: AAs have a higher risk of ACN than AC. Current recommendations to start screening in average-risk AAs at an earlier age may not apply to other black subgroups.

Randomized Controlled Trial: Split-dose and Same-day Large Volume Bowel Preparation for Afternoon Colonoscopy Have Similar Quality of Preparation.

GOALS: We compare bowel cleanliness in patients taking same-day versus split-dose 4-L polyethylene glycol laxative for afternoon colonoscopy. Secondary objectives included patient satisfaction, adverse effects and patient tolerability. BACKGROUND: Afternoon colonoscopies have been associated with inadequate bowel preparation and lower adenoma detection rates. Same-day (morning) or split-dosing of the laxative have improved preparation quality but differences between these options are unclear. MATERIALS AND METHODS: Single-center prospective randomized endoscopist blinded trial. Patients aged 18 years and above prescribed 4-L polyethylene glycol for colonoscopy were randomized into same-day or split-dose preparation. Preparation quality was assessed using the Ottawa Bowel Preparation Scale. Patient satisfaction and side effects was collected using a questionnaire. Intention-to-treat and per-protocol analysis were performed. RESULTS: A total of 300 patients (158 split-dose, 142 same-day) were evaluated. No statistically significant difference was seen on total Ottawa score among the groups (P=0.47) or by individual colonic segments in intent-to-treat and per-protocol analysis. Patients in split-dose group were more likely to complete the entire preparation (P=0.01) but reported more sleep loss (P=0.001). The same-day preparation group reported higher incidence of vomiting (P=0.036). Patients ingesting bowel preparation ≥7 hours before colonoscopy had higher total Ottawa scores (P=0.001). CONCLUSIONS: There were no differences in quality of preparation in patients taking same-day versus split-dose preparation for afternoon colonoscopy. Those receiving same-day preparation were less likely to lose sleep but more likely to have emesis. These differences should be considered when selecting a bowel preparation regimen.

Can polyp detection rate be used prospectively as a marker of adenoma detection rate?

BACKGROUND: Adenoma detection rate (ADR) is a quality indicator for screening colonoscopy, but its calculation is time-consuming. Polyp detection rate (PDR) has been found to correlate with ADR; however, its use as a quality indicator has been criticized out of concern for endoscopists artificially inflating the PDR. We aim to evaluate whether active monitoring affects PDR. METHODS: In March 2015, 14 endoscopists were made aware that their personal PDRs would be tracked monthly as a quality improvement project. Endoscopists received a report of their individual monthly and cumulative PDR, departmental averages, and a benchmark PDR. Following the intervention, data were collected for consecutive patients undergoing average risk screening colonoscopy for six months. PDR, ADR, and adenoma to polyp detection ratio quotient (APDRQ) were compared to a six-month pre-intervention period. RESULTS: 2203 patients were included in the study. There was no statistically significant difference in PDR when comparing pre- and post-intervention (44 vs. 45%, OR 1.04; 95% CI 0.77-1.36). No statistically significant difference in ADR was observed when comparing pre- and post-intervention (29 vs. 30%, OR 1.03; 95% CI 0.64-1.52). There was no statistically significant difference in APDRQ when comparing pre- and post-intervention (0.67 vs. 0.66, OR 0.99; 95% CI 0.69-1.33). CONCLUSIONS: Monthly report cards did not result in a change in PDR or APDRQ. In some environments, PDR can be used as a surrogate marker of ADR, despite endoscopist awareness that PDR is being measured.

Safety of Large-Volume, Same-Day Oral Bowel Preparations During Deep Sedation: A Prospective Observational Study.

BACKGROUND: Colonoscopy quality is directly related to the bowel preparation. It is well established that bowel preparations are improved when at least part of the laxative is ingested on the day of the procedure. However, there is concern that this can result in higher gastric residual volumes (GRV) and increase the risk of pulmonary aspiration. The aim of this study is to evaluate GRV and gastric pH in patients who received day-before bowel preparation versus those ingesting their laxative on the day of colonoscopy under anesthesiologist-directed propofol deep sedation. METHODS: This is a prospective observational study for patients undergoing same-day upper endoscopy and colonoscopy. All included patients had large-volume polyethylene glycol lavage preparation and received propofol sedation. Gastric fluid was collected during the upper endoscopy for volume and pH measurement. RESULTS: The study included 428 patients with 56% receiving same-day laxative preparation and the remainder evening-before preparation. Mean ± SD GRV was 18.1 ± 10.2 mL, 16.3 ± 16.5 mL in each of these preparation groups, respectively (P = .69). GRV ≥ 25 mL or higher than expected GRV adjusted by weight (0.4 mL/kg) were also not different among the study groups (P = .90 and P = .87, respectively). Evaluating GRV based on time since last ingestion of preparation (3-5, 5-7, >7 hours) did not result in any differences (P = .56). Gastric pH was also similar between the bowel preparation groups (P = .23), with mean ± SD of 2.5 ± 1.4 for evening-before and 2.5 ± 1.3 for the same-day preparation. There were more inadequate bowel preparations in day before bowel preparations (P = .001). CONCLUSIONS: A large-volume bowel preparation regimen finished on the day of colonoscopy as close as 3 hours before the procedure results in no increase in GRV or decrease in gastric pH.

A New Scoring System to Predict the Risk for High-risk Adenoma and Comparison of Existing Risk Calculators.

BACKGROUND: Colorectal cancer (CRC) screening guidelines likely over-generalizes CRC risk, 35% of Americans are not up to date with screening, and there is growing incidence of CRC in younger patients. GOALS: We developed a practical prediction model for high-risk colon adenomas in an average-risk population, including an expanded definition of high-risk polyps (≥3 nonadvanced adenomas), exposing higher than average-risk patients. We also compared results with previously created calculators. STUDY: Patients aged 40 to 59 years, undergoing first-time average-risk screening or diagnostic colonoscopies were evaluated. Risk calculators for advanced adenomas and high-risk adenomas were created based on age, body mass index, sex, race, and smoking history. Previously established calculators with similar risk factors were selected for comparison of concordance statistic (c-statistic) and external validation. RESULTS: A total of 5063 patients were included. Advanced adenomas, and high-risk adenomas were seen in 5.7% and 7.4% of the patient population, respectively. The c-statistic for our calculator was 0.639 for the prediction of advanced adenomas, and 0.650 for high-risk adenomas. When applied to our population, all previous models had lower c-statistic results although one performed similarly. CONCLUSIONS: Our model compares favorably to previously established prediction models. Age and body mass index were used as continuous variables, likely improving the c-statistic. It also reports absolute predictive probabilities of advanced and high-risk polyps, allowing for more individualized risk assessment of CRC.

Comparison of Adenoma Detection Rates in Afro-Caribbeans and Non-Hispanic Whites Undergoing First Screening Colonoscopy.

OBJECTIVES: The African American population has a higher prevalence of advanced colon adenomas when compared with non-Hispanic whites and Hispanics, but the risk in other black populations has not been evaluated. Although the Afro-Caribbean population is a significant demographic segment in some regions of the United States, the data are limited on the prevalence of colon adenomas in this group and there is no comparison with a non-Hispanic white population. The objective of our study was to compare the prevalence of adenomas in Afro-Caribbean versus non-Hispanic white populations. METHODS: A total of 880 Afro-Caribbean patients and 1828 non-Hispanic white patients undergoing their first screening colonoscopy between January 2008 and August 2014 was included in the study. RESULTS: A total of 2708 patients met entry criteria for the study. The adenoma detection rate among Afro-Caribbeans was 29% and 31% among non-Hispanic whites. There was no statistically significant difference in the prevalence of adenomas in the two groups (P = 0.28), and the rate of advanced adenomas also was similar in both groups (8.6% in Afro-Caribbeans, 9.2% in non-Hispanic whites; P = 0.60). A multivariate analysis also found no difference in the occurrence of adenomas (P = 0.60) or advanced adenomas (P = 0.99) between Afro-Caribbeans and non-Hispanic whites. CONCLUSIONS: We found a similar adenoma detection rate and advanced adenoma prevalence among Afro-Caribbeans and non-Hispanic whites undergoing their first screening colonoscopy. As such, the Afro-Caribbean population may not have the same risk of colorectal neoplasia as what has been described for African Americans. Based on these results, it is appropriate to initiate colorectal cancer screening for Afro-Caribbeans at age 50 as recommended for non-Hispanic whites.

Crohn's disease presenting as acute gastrointestinal hemorrhage.

Severe gastrointestinal (GI) hemorrhage is a rare complication of Crohn's disease (CD). Although several surgical and non-surgical approaches have been described over the last 2 decades this complication still poses significant diagnostic and therapeutic challenges. Given the relative infrequency of severe bleeding in CD, available medical literature on this topic is mostly in the form of retrospective case series and reports. In this article we review the risk factors, diagnostic modalities and treatment options for the management of CD presenting as GI hemorrhage.

Endoscopic botox injections in therapy of refractory gastroparesis.

Gastroparesis (GP) is a common disease seen in gastroenterology practice particularly in western countries, and it may be underdiagnosed. The available drug therapies for this condition are quite disappointing. Botulinum toxin type A (BT) has been found to be effective therapy in various spastic disorders of smooth muscle of gastrointestinal tract. However, the benefits of BT injections in GP have been unclear. Several retrospective and open label studies have shown clinical advantages of intrapyloric Botulinum toxin type A injections, while two small randomized trials did not show positive results. Therefore, the available published studies yielded conflicting results leading to fading out of botox therapy for GP. We recognize possible clinical benefit of BT injections without any disadvantages of this treatment. We are calling for revisiting the endoscopy guided botox therapy in refractory GP. In this review we discuss important features of these studies pointing out differences in results among them. Differences in patient selection, doses and method of administration of botox toxin in the prior studies may be the cause of conflicting results. The mechanism of action, indications, efficacy and side-effects of BT are reviewed. Finally, we recognize limited evidence to recommend BT in GP and calling attention for future research in this field since no advances in drug management had been made in the last two decades.

Can adjusting BMI for age and sex provide for a better predictor of colonic neoplasia?

OBJECTIVE: The aim of this study was to evaluate the influence of BMI on colonic neoplasia in average-risk patients aged between 40 and 59 years, analyzed by sex. METHODS: A total of 4443 patients aged between 40 and 59 years undergoing a first-time screening or average-risk colonoscopy were included in this study. Data on demographics, smoking, and BMI were collected and correlated to the presence of adenomas and advanced adenomas. RESULTS: We evaluated 1197 colonoscopies in patients aged between 40 and 49 years, and 3246 in those aged between 50 and 59 years. Among men between 40 and 49 years, increasing BMI [odds ratio (OR)=1.05, 95% confidence interval (CI): 1.00-1.09] and BMI of at least 27 (OR=1.95, 95% CI: 1.15-3.29) were predictors of adenomas. Younger men with a BMI of at least 27 were more likely to have proximal adenomas (OR=2.23, 95% CI: 1.14-4.37) but not advanced adenomas. There was no relation between BMI and adenomas in younger women. Among women aged between 50 and 59 years, increasing BMI (OR=1.03, 95% CI: 1.01-1.05) and a BMI of at least 24 (OR=1.43, 95% CI: 1.06-2.94) was found to be correlated with adenomas, and increasing BMI was also found to be associated with proximal adenomas (OR=1.67, 95% CI: 1.13-2.45). Among men aged between 50 and 59 years, there was no relation between BMI and adenomas, but there was a positive correlation for advanced adenomas (OR=1.05, 95% CI: 1.002-1.09). Among women aged between 50 and 59 years, BMI was not predictive of advanced adenomas. CONCLUSION: The association between BMI and adenoma differs by age and sex. If BMI is utilized to refine screening practices for colorectal cancer, its influence on sex and age should be taken into account.

Body mass index and colon cancer screening: the road ahead.

Screening for colorectal cancer (CRC) has been associated with a decreased incidence and mortality from CRC. However, patient adherence to screening is less than desirable and resources are limited even in developed countries. Better identification of individuals at a higher risk could result in improved screening efforts. Over the past few years, formulas have been developed to predict the likelihood of developing advanced colonic neoplasia in susceptible individuals but have yet to be utilized in mass screening practices. These models use a number of clinical factors that have been associated with colonic neoplasia including the body mass index (BMI). Advances in our understanding of the mechanisms by which obesity contributes to colonic neoplasia as well as clinical studies on this subject have proven the association between BMI and colonic neoplasia. However, there are still controversies on this subject as some studies have arrived at different conclusions on the influence of BMI by gender. Future studies should aim at resolving these discrepancies in order to improve the efficiency of screening strategies.