Incomplete Intestinal Metaplasia of the Stomach Is more Related to Bile Reflux than Chronic Gastritis.

OBJECTIVE: Incomplete intestinal metaplasia (IIM) of the stomach is associated with higher risk of progression to dysplasia and gastric cancer than complete intestinal metaplasia (CIM). Whether the causative factors underlying IIM are different from those underlying CIM is currently unknown. In a recent study, bile acids were found to induce gastric intestinal metaplasia (IM) in mice by activating STAT3 signaling and accelerated the development of dysplasia. The aim of this study was to determine whether there are differences in associations between IIM and CIM and clinicopathologic features known to be associated with intestinal metaplasia, bile reflux, and activated STAT3. METHODS: Fifty-two consecutive gastric biopsies with IM were examined for the type of metaplasia, presence of inflammation, and Helicobacter pylori (H. pylori) status. Immunohistochemical staining was performed for phospho-STAT3 (p-STAT3) and evaluated by image analysis. The type of IM was then correlated with relevant clinicopathologic variables and p-STAT3 expression. RESULTS: Seven cases had IIM only, 31 had CIM only, and 14 had both CIM and IIM (CIIM). Significantly fewer cases with IIM had chronic gastritis than either CIM or CIIM (43%, 93%, 79%, respectively, p=0.005). H. pylori was not detected in any of the IIM cases but was positive in 29% of CIM and 29% of CIIM. Fifty-seven percent of patients with IIM had a history of cholecystectomy compared to 25% of those with CIM and 23% of those with CIIM. The mean BMI was 32.3 kg/m2 for patients with IIM compared to 28 kg/m2 for those with CIM and 31.2 kg/m2 for those with CIIM. Median p-STAT3 for biopsies with was IIM was 6.36 compared to 3.54 for CIM and 6.27 for CIIM. Reactive gastropathy was present in 57% of biopsies with IIM, 39% of CIM and 50% of CIIM. CONCLUSION: In contrast to CIM, IIM is significantly less likely to be associated with chronic gastritis. CIIM also tended to be less associated with H. pylori infection and more associated with reactive gastropathy, history of cholecystectomy, higher BMI, and higher median p-STAT3. These results tend to suggest that IIM is probably more likely to be associated with bile reflux than H. pylori-associated gastritis. Larger studies are needed to confirm these findings.Presented in part at Digestive Disease Week 2023, Chicago, IL, May 6, 2023.

Definition of factor Xa inhibitor-related, life-threatening gastrointestinal bleeding and guidance on when to use reversal therapy: A Delphi panel.

Objective: To define and contextualize life-threatening gastrointestinal (GI) bleeding in the setting of factor Xa (FXa) inhibitor therapy and to derive a consensus-based, clinically oriented approach to the administration of FXa inhibitor reversal therapy. Methods: We convened an expert panel of clinicians representing specialties in emergency medicine, gastroenterology, vascular medicine, and trauma surgery. Consensus was reached among the clinician panelists using the Delphi technique, which consisted of 2 survey questionnaires followed by virtual, real-time consensus-building exercises. Results: Hypovolemia and hemodynamic instability were considered the most important clinical signs of FXa inhibitor-related, life-threatening GI bleeds. Clinician panelists agreed that potentially life-threatening GI bleeding should be determined on the basis of hemodynamic instability, signs of shock, individual patient characteristics, and clinical judgment. Last, the panel agreed that all patients with life-threatening, FXa inhibitor-associated GI bleeding should be considered for FXa inhibitor reversal therapy; the decision to reverse FXa inhibition should be individualized, weighing the risks and benefits of reversal; and when reversal is elected, therapy should be administered within 1 h after initial emergency department evaluation, when possible. Conclusions: Consensus-based definitions of life-threatening GI bleeding and approaches to FXa inhibitor reversal centered on hemodynamic instability, signs of shock, individual patient characteristics, and clinical judgment. The results from this Delphi panel may inform clinical decision-making for the treatment of patients experiencing GI bleeding associated with FXa inhibitor use in the emergency department setting.

Prevalence of Fibromyalgia and Chronic Fatigue Syndrome among Individuals with Irritable Bowel Syndrome: An Analysis of United States National Inpatient Sample Database.

Background and Aim: Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder associated with other somatic disorders. We studied the prevalence and predictors of fibromyalgia and chronic fatigue syndrome (CFS) in IBS patients. Methods: We used the National Inpatient Sample and included hospitalization of individuals with IBS, using ICD-10 codes, from 2016-2019. The prevalence and predictors of fibromyalgia and CFS in IBS patients were studied. Univariate and multivariate patient- and hospital-level regression models were used to calculate the adjusted odds of fibromyalgia and CFS in the IBS patient population. Results: Of 1,256,325 patients with an ICD-10 code of IBS included in the study, 10.73% (134,890) also had ICD-10 codes for fibromyalgia and 0.42% (5220) for CFS. The prevalence of fibromyalgia and CFS was significantly higher in IBS patients (adjusted odds ratio (AOR) 5.33, 95% confidence interval (CI) 5.24-5.41, p < 0.001, and AOR 5.40, 95% CI 5.04-5.78, p < 0.001, respectively) compared to the general adult population without IBS. IBS-diarrhea, IBS-constipation, and IBS-mixed types were independently associated with increased odds of fibromyalgia and CFS. Increasing age (AOR 1.02, 95% CI 1.01-1.04, p 0.003; AOR 1.02, 95% CI 1.01-1.03, p 0.001), female gender (AOR 11.2, 95% CI 11.1-11.4, p < 0.001; AOR 1.86, 95% CI 1.78-1.93, p < 0.001) and white race (AOR 2.04, 95% CI 1.95-2.12, p < 0.001; AOR 1.69, 95% CI 1.34-2.13, p < 0.001) were independent predictors of increased odds of fibromyalgia and CFS, respectively. Conclusions: It appears that IBS is associated with an increased prevalence of somatic disorders such as fibromyalgia and CFS.

Efficacy and Safety of Naloxegol in Patients with Chronic Non-Cancer Pain Who Experience Opioid-Induced Constipation: A Pooled Analysis of Two Global, Randomized Controlled Studies.

Objective: This study evaluates the onset, magnitude, and consistency of improvement of opioid-induced constipation (OIC) symptoms with naloxegol treatment. Methods: This was a pooled analysis of two Phase 3, double-blind, randomized, placebo-controlled studies (KODIAC-04/05, NCT01309841/NCT01323790) in patients with chronic non-cancer pain and OIC treated with naloxegol 25mg or 12.5mg daily. This analysis assessed improvements in response rates, frequency of spontaneous bowel movement (SBM) and complete SBMs (CSBM), OIC constipation symptoms (straining, stool consistency), time to first post-dose SBM and CSBM, and onset of adverse events over the 12-week period. Subjects: The population of 1337 subjects had a mean age of 52 years and mean duration of opioid use of 3.6 years at baseline. Mean SBM frequency was 1.4/week. Results: Naloxegol 25mg and 12.5mg demonstrated significantly higher response rates vs placebo (PBO) [41.9% (P < 0.001), 37.8% (P = 0.008), 29.4% respectively]. Rapid (within 1 week) and sustained (over 12 weeks) symptom improvement was significantly greater for naloxegol vs PBO (P < 0.05). Both doses showed statistically significant and clinically meaningful improvements in straining, stool consistency, number of SBMs and CSBMs/wk. Significantly shorter times to first post-dose SBM and CSBM were observed with naloxegol vs PBO (SBM HR: 25mg = 1.90, 12.5mg= 1.60; CSBM HR: 25mg = 1.42, 12.5mg = 1.36; P < 0.001 for each regimen). Adverse events occurred more frequently in the naloxegol 25mg group and were most frequently reported during the first week. Conclusion: In patients with chronic non-cancer pain, naloxegol 25mg and 12.5mg demonstrated significantly higher response rates and rapid and sustained improvements in OIC symptoms compared with PBO.

Plecanatide for the treatment of chronic idiopathic constipation and irritable bowel syndrome with constipation: Post hoc analyses of placebo-controlled trials in adults with severe constipation.

BACKGROUND: Patients with chronic idiopathic constipation (CIC) and irritable bowel syndrome with constipation (IBS-C) often experience severe symptoms. The current aim was to evaluate plecanatide in adults with CIC or IBS-C with severe constipation. METHODS: Data were analyzed post hoc from randomized, placebo-controlled trials (CIC [n = 2], IBS-C [n = 2]) of plecanatide 3 mg, 6 mg, or placebo administered for 12 weeks. Severe constipation was defined as no complete spontaneous bowel movements (CSBMs) and an average straining score ≥3.0 (CIC; 5-point scale) or ≥8.0 (IBS-C; 11-point scale) during a 2-week screening. Primary efficacy endpoints were durable overall CSBM responders (CIC: ≥3 CSBMs/week, plus increase from baseline of ≥1 CSBM/week, for ≥9 of 12 weeks, including ≥3 of the last 4 weeks) and overall responders (IBS-C: ≥30% reduction from baseline in abdominal pain and ≥1 CSBM/week increase for ≥6 of 12 weeks). KEY RESULTS: Severe constipation was observed in 24.5% (646/2639) and 24.2% (527/2176) of CIC and IBS-C populations, respectively. The CIC durable overall CSBM response rate (plecanatide 3 mg, 20.9%; plecanatide 6 mg, 20.2%; placebo, 11.3%) and IBS-C overall response rate (plecanatide 3 mg, 33.0%; plecanatide 6 mg, 31.0%; placebo, 19.0%) were significantly greater with plecanatide versus placebo (p ≤ 0.01 for all). Median time to first CSBM in CIC and IBS-C populations were significantly shorter with plecanatide 3 mg versus placebo (p = 0.01 for both). CONCLUSIONS AND INFERENCES: Plecanatide was effective in the treatment of severe constipation in adults with CIC or IBS-C.

ACR Appropriateness Criteria® Right Upper Quadrant Pain: 2022 Update.

Acute right upper quadrant pain is one of the most common presenting symptoms in hospital emergency departments, as well as outpatient settings. Although gallstone-related acute cholecystitis is a leading consideration in diagnosis, a myriad of extrabiliary sources including hepatic, pancreatic, gastroduodenal, and musculoskeletal should also be considered. This document focuses on the diagnostic accuracy of imaging studies performed specifically to evaluate acute right upper quadrant pain, with biliary etiologies including acute cholecystitis and its complications being the most common. An additional consideration of extrabiliary sources such as acute pancreatitis, peptic ulcer disease, ascending cholangitis, liver abscess, hepatitis, and painful liver neoplasms remain a diagnostic consideration in the right clinical setting. The use of radiographs, ultrasound, nuclear medicine, CT, and MRI for these indications are discussed. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Colonic Eosinophilia: Clinicopathologic Study of Paired Right and Left Colon Biopsies from 276 Patients.

OBJECTIVE: This study evaluated differences in eosinophil (Eos) count in the right colon (RC) and left colon (LC) relative to known clinical and pathologic features. METHODS: H&E slides from 276 subjects with biopsies taken from both RC and LC were reviewed. Eos/mm2 were counted in the area with highest concentration then correlated with clinical and pathologic findings for RC and LC. RESULTS: There were higher numbers of Eos/mm2 in RC than in LC (mean 177 vs 122, respectively p<0.0001), and there was significant positive correlation between Eos numbers in the two locations (r=0.57, p<0.001). In RC, the mean Eos/mm2 was 242 with active chronic colitis, 195 with inactive chronic colitis, 160 in microscopic colitis, 144 in quiescent IBD, and 142 with normal histology (p<0.001), and was higher in males (204 vs 164, p=0.022). In LC, mean Eos/mm2 was 186 with active chronic colitis, 168 with inactive chronic colitis, 154 in microscopic colitis, 82 in quiescent IBD, and 84 with normal histology (p<0.001), and was higher in males (154 vs 107, p<0.001). In biopsies with normal histology, RC showed higher mean Eos/mm2 in Asian patients (228 vs 139, p=0.019), and patients with history of UC (205 vs 136, p=0.004), but was not significantly different in patients with or without irritable bowel syndrome with diarrhea (IBS-D) or history of Crohn's disease (CD). In LC the mean Eos/mm2 was higher in males (102 vs 77, p=0.036), and history of CD (117 vs 78, p=0.007), but was not significantly different in patients with or without IBS-D or history of UC. The number of Eos/mm2 was greater in biopsies performed in the summer than during other seasons of the year. CONCLUSION: The mean number of Eos/mm2 in colorectal biopsies varies significantly by location, histopathologic changes, clinical diagnosis, season, gender and ethnicity. Of particular interest is the association between high Eos/mm2 in RC biopsies with otherwise normal histology and clinical history of UC, and in LC biopsies with clinical history of CD. Additional larger and prospective studies that include normal healthy volunteers are needed to establish a reliable cutoff for the histopathologic diagnosis of eosinophilic colitis, taking into consideration the biopsy site within the colon and rectum, as well as patient gender and ethnicity.Presented in part at the annual American College of Gastroenterology meeting, San Antonio, TX October 2019.

Transient alterations in plasma sodium concentrations with NER1006 bowel preparation: an analysis of three phase III, randomized clinical trials.

BACKGROUND: This analysis characterized changes in sodium levels in patients receiving the 1 L polyethylene glycol-based preparation NER1006. METHODS: Data were pooled from three phase III, randomized clinical trials. A post hoc subanalysis included adults who received a 2-day split-dose (evening/morning) NER1006 regimen, a 1-day split-dose (morning only) regimen, or evening-before regimen and had an increase in sodium concentrations from normal to above the upper limit of normal (143-148 mmol/L) at ≥ 1 of three post-treatment visits. Blood samples were collected at baseline, day of colonoscopy (visit 2), 2 ± 1 days post-colonoscopy (visit 3), and 7 ± 1 days post-colonoscopy (visit 4). RESULTS: A total of 214 of 1028 patients were included. Of the 214 patients, sodium concentration increased from a mean baseline value of 141.8 mmol/L to a mean of 147.1 mmol/L (median increase from baseline of approximately 5 mmol/L). The mean sodium concentration was within normal range at visit 3 (142.3 mmol/L) and visit 4 (142.4 mmol/L), as was the median sodium concentration. Overall, ~ 90% of patients had a normal serum concentration at visits 3 and 4. Based on day of colonoscopy test results, there were four adverse events involving hypernatremia (0.4% of 1028), which were mild and did not require medical intervention; sodium levels returned to normal range by visit 3. CONCLUSION: NER1006 was associated with small, transient increases in sodium levels that were not considered clinically significant. Trial registration NOCT (ClinicalTrials.gov: NCT02254486 [registered October 2, 2014]), MORA (ClinTrials.gov: NCT02273167 [registered October 23, 2014]; EudraCT number: 2014-002185-78 [registered August 13, 2014]), DAYB (ClinicalTrials.gov: NCT02273141 [registered October 23, 2014]; EudraCT Number: 2014-002186-30 [registered August 12, 2014]).

ACR Appropriateness Criteria® Staging of Colorectal Cancer: 2021 Update.

Preoperative imaging of rectal carcinoma involves accurate assessment of the primary tumor as well as distant metastatic disease. Preoperative imaging of nonrectal colon cancer is most beneficial in identifying distant metastases, regardless of primary T or N stage. Surgical treatment remains the definitive treatment for colon cancer, while organ-sparing approach may be considered in some rectal cancer patients based on imaging obtained before and after neoadjuvant treatment. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

A novel duodenal-release formulation of caraway oil and L-menthol is a safe, effective and well tolerated therapy for functional dyspepsia.

BACKGROUND: A randomized, placebo-controlled clinical trial (FDREST) of a novel formulation of caraway oil and L-menthol (COLM-SST) demonstrated symptom relief in patients with functional dyspepsia (FD). Two follow-up studies were conducted to evaluate patient satisfaction, self-regulated dosing, and long-term safety data: FDACT, Functional Dyspepsia Adherence and Compliance Trial, and FDSU36, Functional Dyspepsia Safety Update at 36 months. METHODS: A patient reported outcomes (PRO) questionnaire was designed and distributed online to assess real-world satisfaction and dosing frequency of open-label COLM-SST in patients with FD. A separate study analyzing voluntary safety surveillance data evaluated the frequency and severity of reported adverse events (AEs). RESULTS: A total of 600 FD patients were enrolled in the PRO study. Ninety five percent of respondents reported a major or moderate improvement in their FD symptoms and 91.7% indicated a major or moderate improvement in quality of life (QOL) using COLM-SST. Between 1 and 4 capsules were consumed daily by 91.2% of respondents, with 56.2% taking them before meals. Symptom relief was rapid, with 86.4% of respondents indicating relief within 2 h of taking COLM-SST. Few adverse events (AEs) were reported (0.0187%) by patients using COLM-SST. No serious AEs were identified. CONCLUSION: COLM-SST is safe, well tolerated, and provides rapid relief of FD symptoms. These findings, demonstrated in the FDREST trial, were further supported by a large prospective PRO study evaluating self-regulated dosing frequency, symptom improvement, and QOL. COLM-SST was well-tolerated based on review of AE data at 36 months.

The Present and Future of Colorectal Cancer Screening.

There have been multiple recent updates for recommendations pertaining to colorectal cancer (CRC) screening. Among the most notable is the recommendation from several guideline-issuing bodies to initiate CRC screening examinations at 45 years of age for individuals at average risk for CRC. Current CRC screening methods include stool-based tests and colon visualization examinations. Currently recommended stool-based tests include fecal immunochemical testing, high-sensitivity guaiac-based fecal occult blood testing, and multitarget stool DNA testing. Visualization examinations include colonoscopy, computed tomography colonography, colon capsule endoscopy, and flexible sigmoidoscopy. Although these screening tests have shown encouraging results for CRC detection, there are important differences between these testing modalities for precursor lesion detection and management. In addition, emerging CRC screening methods are being developed and evaluated. However, additional large, multicenter clinical trials in diverse populations are needed to validate the diagnostic accuracy and generalizability of these new tests. This article reviews the recently updated CRC screening recommendations and current and emerging testing options.

Alterations in MAdCAM1-Positive Mucosal Capillaries and Integrin a4b7-Positive Lymphocytes in Crohn's Disease Treated with Anti-TNFα Biologics.

OBJECTIVE: To elucidate the reasons for the decreased effectiveness of Vedolizumab (VDZ) treatment in patients with Crohn's disease (CD) previously treated (CD-T) with anti-TNF-α biologics. METHODS: Immunohistochemical staining was performed on sections of formalin-fixed paraffin-embedded ileocolonic biopsies using antibodies for the mucosal addressin molecule (MAdCAM-1) and Etrolizumab. RESULTS: The mean number of MAdCAM-1 positive capillaries (MAdCAM-1-C) was 3 in controls, 8.5 in CD, 5.37 in CD-T, 5.7 in ulcerative colitis (UC), and 3.1 in lymphocytic colitis (LC) (p=0.0032). When all biopsies with inflammatory bowel disease (IBD) in this series were considered together, the number of MAdCAM-1-C increased with an increased histologic activity score (HAS) (p<0.001). The mean MAd-CAM-1-C was lower in CD-T than CD (5.37 vs. 8.5, p=0.0362), even in cases with high HAS (6.46 vs. 9.5, p=0.073). Two of 6 (33%) controls, 4 of 6 (67%) CD, 9 of 16 (56%) CD-T, 6 of 7 (86%) UC, and 0 of 8 (0%) LC showed Etrolizumab-positive lymphocytes (E-Ly, p=0.0106). IBD biopsies positive for E-Ly were associated with higher HAS (p=0.0546). MAdCAM-1-C was heterogenous in some IBD cases. CONCLUSIONS: Our results suggest that treatment with anti-TNF-α reduces the number of MAdCAM-1-C in CD, even in biopsies with high HAS. This suggests that high inflammation in such cases obviously failed to respond to anti-TNF-α, may be less dependent on the migration of a4b7-lymphocytes to the inflamed mucosa, and therefore may not optimally respond to VDZ treatment.Presented in part at the Digestive Diseases Week meeting, San Diego, CA, May 2019. Supported by Takeda Pharmaceuticals.

Lymphocytic Esophagitis Is Not Similar to Eosinophilic Esophagitis Except for Seasonal Variation.

OBJECTIVE: Unlike eosinophilic esophagitis (EoE), there is no consensus on the minimum number of intraepithelial lymphocytes (IEL) that is diagnostic of lymphocytic esophagitis (LyE). The aim of this study was to determine whether significant correlations exist between the numbers of intraepithelial lymphocytes (IEL) in esophageal biopsies and clinical and endoscopic manifestations usually associated with EoE. METHODS: H&E slides from esophageal biopsies from 330 patients were reviewed. The number of IEL and intraepithelial eosinophils (IEE) per mm2 was counted in the area with the highest concentration in each biopsy. The numbers were then correlated with clinical and endoscopic findings. RESULTS: As expected, a higher number of IEE was significantly associated with food impaction (p=0.001), dysphagia (p=0.021), esophageal stricture (p=0.017), rings (P<0.0001), and furrows (p<0.0001). By contrast, there was no significant association between increased IEL and any of the aforementioned clinical and endoscopic features in the original 330 patients or in a subset of 233 patients with no IEE. Interestingly, the number of both IEE and IEL varied significantly by the season when the biopsy was obtained, being lowest in the fall and highest in the spring (p=0002 for IEE and p<0.0001 for IEL). CONCLUSION: In esophageal biopsies, increased IEL has no significant correlation with food impaction or dysphagia or with esophageal stricture, rings, or furrows. There is significant variation in the number of IEL depending on the season when the biopsy is obtained, which has not been previously reported.

ACR Appropriateness Criteria® Radiologic Management of Lower Gastrointestinal Tract Bleeding: 2021 Update.

Diverticulosis remains the commonest cause for acute lower gastrointestinal tract bleeding (GIB). Conservative management is initially sufficient for most patients, followed by elective diagnostic tests. However, if acute lower GIB persists, it can be investigated with colonoscopy, CT angiography (CTA), or red blood cell (RBC) scan. Colonoscopy can identify the site and cause of bleeding and provide effective treatment. CTA is a noninvasive diagnostic tool that is better tolerated by patients, can identify actively bleeding site or a potential bleeding lesion in vast majority of patients. RBC scan can identify intermittent bleeding, and with single-photon emission computed tomography, can more accurately localize it to a small segment of bowel. If patients are hemodynamically unstable, CTA and transcatheter arteriography/embolization can be performed. Colonoscopy can also be considered in these patients if rapid bowel preparation is feasible. Transcatheter arteriography has a low rate of major complications; however, targeted transcatheter embolization is only feasible if extravasation is seen, which is more likely in hemodynamically unstable patients. If bleeding site has been previously localized but the intervention by colonoscopy and transcatheter embolization have failed to achieve hemostasis, surgery may be required. Among patients with obscure (nonlocalized) recurrent bleeding, capsule endoscopy and CT enterography can be considered to identify culprit mucosal lesion(s). The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Patient experience with NER1006 as a bowel preparation for colonoscopy: a prospective, multicenter US survey.

BACKGROUND: NER1006 (Plenvu®, Salix Pharmaceuticals, Bridgewater, NJ) is a 1 L polyethylene glycol bowel preparation indicated for colonoscopy in adults. A US online survey assessed real-world ease of use and treatment satisfaction in individuals who received NER1006. METHODS: Adults were recruited from 444 US community gastrointestinal practices and provided a kit number for enrollment into an online survey to be completed within 2 weeks. Survey questions evaluated colonoscopy history and prior bowel preparation(s) prescribed, patient experience during NER1006 administration, and patient satisfaction with the bowel preparation process. A 9-point predefined grading scale was used to evaluate ease of NER1006 preparation and consumption (range, 1 "very difficult" to 9 "very easy"); the perceived importance of volume requirement and clear liquid options (range, 1 "not important at all" to 9 "very important"); and patient satisfaction (range, 1 "not satisfied at all" to 9 "very satisfied"). RESULTS: 1630 patients were enrolled, 1606 underwent colonoscopy, and 1598 completed the survey between September 15, 2018 and February 28, 2019. Among 1606 patients who had a colonoscopy, 62.5% were female, and the mean patient age was 54.4 years (range 18-89 years). Most patients (74.7%) did not report a family history of colon cancer, 62.6% had undergone prior colonoscopy, and 64.8% were undergoing colonoscopy for routine colorectal cancer screening. A majority (76.1%) of patients who completed the survey reported that NER1006 was very easy to prepare and take, and 89.9% were very or moderately satisfied with NER1006 overall. Most (97.6%) patients reported consuming all or most of the bowel preparation. Among 1005 patients with previous bowel preparation use, 84.7% indicated that their experience with NER1006 was much better or better (65.3%) or about the same (19.4%) compared with previously used bowel preparations, while only 15.3% rated NER1006 as worse or much worse. CONCLUSIONS: In this first real-world, US multicenter survey, patient-reported experience with NER1006 as a bowel preparation for colonoscopy was favorable and adherence was high. The majority of patients were very or moderately satisfied with the overall experience and found it much better/better than previously used bowel preparations. TRIAL REGISTRATION: Not applicable.

Multicentre, prospective, randomised study comparing the diagnostic yield of colon capsule endoscopy versus CT colonography in a screening population (the TOPAZ study).

OBJECTIVE: Colon capsule endoscopy (CCE) has shown promise for colorectal neoplasia detection compared with optical colonoscopy (OC), but has not been compared with other screening tests in average risk screening patients. DESIGN: Patients 50 to 75 years of age (African Americans, 45-75 years) were randomised to CCE or CT colonography (CTC) and subsequent blinded OC. The primary endpoint was diagnostic yield of polyps ≥6 mm with CCE or CTC. Secondary endpoints included accuracy for size and histology, examination completeness, number/proportion of subjects with polyps and adenomas ≥6 mm and ≥10 mm, subject satisfaction and safety. RESULTS: From 320 enrolled subjects, data from 286 (89.4%) were evaluable. The proportion of subjects with any polyp ≥6 mm confirmed by OC was 31.6% for CCE versus 8.6% for CTC (pPr non-inferiority and superiority=0.999). The diagnostic yield of polyps ≥10 mm was 13.5% with CCE versus 6.3% with CTC (pPr non-inferiority=0.9954). The sensitivity and specificity of CCE for polyps ≥6 mm was 79.2% and 96.3% while that of CTC was 26.8% and 98.9%. The sensitivity and specificity of CCE for polyps ≥10 mm was 85.7% and 98.2% compared with 50% and 99.1% for CTC. Both tests were well tolerated/safe. CONCLUSION: CCE was superior to CTC for detection of polyps ≥6 mm and non-inferior for identification of polyps ≥10 mm. CCE should be considered comparable or superior to CTC as a colorectal neoplasia screening test, although neither test is as effective as OC. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov no: NCT02754661.

Kras mutation rate precisely orchestrates ductal derived pancreatic intraepithelial neoplasia and pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer-related death in the United States. Despite the high prevalence of Kras mutations in pancreatic cancer patients, murine models expressing the oncogenic mutant Kras (Krasmut) in mature pancreatic cells develop PDAC at a low frequency. Independent of cell of origin, a second genetic hit (loss of tumor suppressor TP53 or PTEN) is important for development of PDAC in mice. We hypothesized ectopic expression and elevated levels of oncogenic mutant Kras would promote PanIN arising in pancreatic ducts. To test our hypothesis, the significance of elevating levels of K-Ras and Ras activity has been explored by expression of a CAG driven LGSL-KrasG12V allele (cKras) in pancreatic ducts, which promotes ectopic Kras expression. We predicted expression of cKras in pancreatic ducts would generate neoplasia and PDAC. To test our hypothesis, we employed tamoxifen dependent CreERT2 mediated recombination. Hnf1b:CreERT2;KrasG12V (cKrasHnf1b/+) mice received 1 (Low), 5 (Mod) or 10 (High) mg per 20 g body weight to recombine cKras in low (cKrasLow), moderate (cKrasMod), and high (cKrasHigh) percentages of pancreatic ducts. Our histologic analysis revealed poorly differentiated aggressive tumors in cKrasHigh mice. cKrasMod mice had grades of Pancreatic Intraepithelial Neoplasia (PanIN), recapitulating early and advanced PanIN observed in human PDAC. Proteomics analysis revealed significant differences in PTEN/AKT and MAPK pathways between wild type, cKrasLow, cKrasMod, and cKrasHigh mice. In conclusion, in this study, we provide evidence that ectopic expression of oncogenic mutant K-Ras in pancreatic ducts generates early and late PanIN as well as PDAC. This Ras rheostat model provides evidence that AKT signaling is an important early driver of invasive ductal derived PDAC.

ACR Appropriateness Criteria® Liver Lesion-Initial Characterization.

Incidental liver masses are commonly identified on imaging performed for other indications. Since the prevalence of benign focal liver lesions in adults is high, even in patients with primary malignancy, accurate characterization of incidentally detected lesions is of paramount clinical importance. This document reviews utilization of various imaging modalities for characterization of incidentally detected liver lesions, discussed in the context of several clinical scenarios. For each clinical scenario, a summary of current evidence supporting the use of a given diagnostic modality is reported. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.