Multi-focal dysplasia is associated with high recurrence rates after successful ablation of dysplastic Barrett's esophagus.

BACKGROUND & AIMS: Barrett's esophagus (BE) might recur after complete eradication of intestinal metaplasia (CEIM). We investigated  factors associated with recurrence of BE after successful Radiofrequency ablation (RFA). METHODS: A longitudinal study of BE patients with dysplasia treated with RFA from 2014 to 2021 in two large referral centers. Recurrence was identified in histologic specimens. Factors associated with post-RFA recurrence were analyzed using Cox regression analysis. RESULTS: A total of 728 patients with BE were identified, 118 had underwent RFA, and 113 had sufficient follow up time. Mean age was 63.7 (±11.7) years, 73.5% were males, 59.3% had long segment of BE, and 30.1% had multifocal dysplasia. During 340.8 patient-years of follow-up, 15 patients (13.3%) had recurrence of BE, which represent an incidence rate of 4.41% per patient-year. Incidence rate of recurrence with dysplasia was 1.17% per patient-year. Multifocal dysplasia, number of RFA sessions, and endoscopic resection before RFA were associated with risk of recurrence in univariate analysis. However, in cox regression analysis only multifocal dysplasia (HR 10.99; 95% CI 2.83-22.62, p = 0.001) was associated with post-RFA recurrence. CONCLUSION: Total recurrence rates after CEIM are low, and multifocal dysplasia before the ablative therapy is significantly associated with BE recurrence after CEIM. Patients with multifocal dysplasia should be monitored rigorously after successful ablation.

Development and validation of a prediction model for histologic progression in patients with nondysplastic Barrett's esophagus.

OBJECTIVES: Patients with Barrett's esophagus (BE) are at risk of progression to esophageal adenocarcinoma (EAC). We developed a model to predict histologic progression in patients with nondysplastic BE (NDBE). METHODS: A longitudinal study in three referral centers was performed between January 2010 and December 2019. As progression to low-grade dysplasia (LGD) can be considered an indication for ablative therapy, the study end-point was histopathologic progression to LGD, high-grade dysplasia, or EAC at 3 years after diagnosis. We used logistic regression to create the model. Seventy percent of the cohort were used to stem the model and the remaining 30% for internal validation. RESULTS: A total of 542 patients were included, 69.4% of whom were male, mean age 62.2 years. Long-segment BE at index endoscopy was diagnosed in 20.8% of the patients. After a mean follow-up of 6.7 years, 133 patients (24.5%) had histologic progression. Our model identified a neutrophil-to-lymphocyte ratio (odds ratio [OR] 2.08, 95% confidence interval [CI] 1.77-2.32, P < 0.001), BE length (OR 1.22, 95% CI 1.09-1.36, P < 0.001), age (OR 1.03, 95% CI 1.02-1.05, P = 0.02), smoking (OR 1.66, 95% CI 1.09-2.75, P = 0.04), and renal failure (OR 1.51, 95% CI 0.93-2.43, P = 0.07) as predictors of histologic progression at 3 years. The areas under the receiver operating characteristic curves of this model were 0.88 and 0.76 in the training and validation cohorts, respectively. CONCLUSION: This novel, internally validated model may predict histologic progression, even in patients with NDBE who generally have low rates of progression over time, and may contribute to enhanced patient selection for more intense surveillance programs.

Medical cannabis for inflammatory bowel disease: real-life experience of mode of consumption and assessment of side-effects.

OBJECTIVE: Use of medical cannabis for improving symptoms of inflammatory bowel disease is increasing. However, reports on long-term outcomes are lacking. This prospective, observational study assessed the effects of licensed cannabis use among patients with inflammatory bowel disease. METHODS: Dose and mode of consumption, adverse events, use of other medications, and long-term effects were evaluated among 127 patients with inflammatory bowel disease using legalized medical cannabis. Blood count, albumin, and C-reactive protein were assessed before, 1 month, and at least 1 year after medical cannabis therapy was initiated. Questionnaires on disease activity, patient function, and signs of addiction were completed by patients and by a significant family member to assess its effects. RESULTS: The average dose used was 31 ± 15 g/month. The average Harvey-Bradshaw index improved from 14 ± 6.7 to 7 ± 4.7 (P < 0.001) during a median follow-up of 44 months (interquartile range, 24-56 months). There was a slight, but statistically significant, average weight gain of 2 kg within 1 year of cannabis use. The need for other medications was significantly reduced. Employment among patients increased from 65 to 74% (P < 0.05). We conclude that the majority of inflammatory bowel disease patients using cannabis are satisfied with a dose of 30 g/month. We did not observe negative effects of cannabis use on the patients' social or occupational status. CONCLUSIONS: Cannabis use by inflammatory bowel disease patients can induce clinical improvement and is associated with reduced use of medication and slight weight gain. Most patients respond well to a dose of 30 g/month, or 21 mg Δ9-tetra- hydrocannabinol (THC) and 170 mg Cannabidiol (CBD) per day.

Sense of coherence in people with and without inflammatory bowel diseases - is there a difference?

BACKGROUND AND AIMS: Sense of coherence (SOC) is a theoretical concept reflecting a person's resources and orientation, which enable individuals to cope with stressors in a health-promoting manner. In several multifactorial chronic diseases, such as diabetes mellitus and systemic lupus erythematosus, SOC was correlated with disease development. It was also related with the emotional distress in patients with inflammatory bowel disease (IBD).The aim of this study was to investigate the possible correlation between low SOC scores and the presence of IBD. METHODS: A total of 183 Crohn's disease (CD) and 71 ulcerative colitis (UC) patients completed questionnaires including demographic data and the 13 items for the SOC questionnaire. The IBD patients were matched to 124 healthy people according to age, gender, education, employment status and marital status. RESULTS: In the CD cohort, 96 patients were matched to the healthy cohort according to the propensity score value, and in the UC cohort 57 were matched. Patients with Crohns' disease had a median SOC score of 63 (IQR 56-71), and healthy matching controls of 62.5 (IQR 55.25- 68.75) p=0.369. Patients with ulcerative patients had a median SOC score of 66 (IQR 56-73) and healthy controls 62 (IQR 55-69) p=0.354. CONCLUSIONS: In our study SOC was not related to the development of IBD. The question of whether SOC is associated with the development of chronic disease and particularly with IBD remains open.

Low-Dose Cannabidiol Is Safe but Not Effective in the Treatment for Crohn's Disease, a Randomized Controlled Trial.

BACKGROUND: Cannabidiol (CBD) is an anti-inflammatory cannabinoid shown to be beneficial in a mouse model of IBD. Lacking any central effect, cannabidiol is an attractive option for treating inflammatory diseases. AIM: To assess the effects of cannabidiol on Crohn's disease in a randomized placebo-controlled trial. PATIENTS AND METHODS: Twenty patients aged 18-75 years with a Crohn's disease activity index (CDAI) >200 were randomized to receive oral (10 mg) CBD or placebo twice daily. Patients did not respond to standard treatment with steroids (11 patients), thiopurines (14), or TNF antagonists (11). Disease activity and laboratory parameters were assessed during 8 weeks of treatment and 2 weeks thereafter. Other medical treatment remained unchanged. RESULTS: Of 20 patients recruited 19 completed the study. Their mean age was 39 ± 15, and 11 were males. The average CDAI before cannabidiol consumption was 337 ± 108 and 308 ± 96 (p = NS) in the CBD and placebo groups, respectively. After 8 weeks of treatment, the index was 220 ± 122 and 216 ± 121 in the CBD and placebo groups, respectively (p = NS). Hemoglobin, albumin, and kidney and liver function tests remained unchanged. No side effects were observed. CONCLUSION: In this study of moderately active Crohn's disease, CBD was safe but had no beneficial effects. This could be due to lack of effect of CBD on Crohn's disease, but could also be due to the small dose of CBD, the small number of patients in the study, or the lack of the necessary synergism with other cannabinoids. Further investigation is warranted. CLINICALTRIALS.GOV: NCT01037322.

[BILE DUCT PROBLEMS - ENDOSCOPIC SOLUTIONS].

Patients with symptomatic bile duct stones are at increased risk for complications, which can be life-threatening. In the last four decades, with the development of endoscopic retrograde cholangiopancreatography (ERCP) and biliary sphincterotomy, endoscopic treatment has almost totally replaced surgical treatment of bile duct stones. In addition, a variety of benign and malignant conditions such as iatrogenic strictures (post cholecystectomy/post liver transplant), PSC, papillary adenoma or malignant tumors of bile duct or pancreas, are now amenable to endoscopic treatment. In the early years, ERCP served as a diagnostic and therapeutic tool With the development of non-invasive imaging alternatives, ERCP became a purely therapeutic procedure. However, in recent years, advanced technologies have restored diagnostic abilities to FRCP.

Increased TERC gene copy number and cells in senescence in primary sclerosing cholangitis compared to colitis and control patients.

OBJECTIVE: Primary sclerosing cholangitis (PSC) is a chronic cholestatic disorder that involves inflammatory and fibrotic changes in the bile ducts. Up to 80% of patients have concomitant inflammatory bowel disease (IBD) with colitis. PSC patients are predisposed to develop hepatobiliary, colonic and other extrahepatic malignancies, probably related to inflammatory processes that might promote carcinogenesis. Telomerase is an enzyme complex that lengthens telomeres and has enhanced expression in numerous malignancies. In this study, we evaluated the TERC gene copy number, the proportion of cells in senescence and the amount of fragmentation in the senescent state. METHODS: Fluorescence in situ hybridization (FISH) for the TERC gene was applied to lymphocytes retrieved from PSC (N=19), colitis (N=20) and healthy control patients (N=20) to determine the TERC copy number. On the same FISH slides, cells stained with DAPI were also analyzed for senescence-associated heterochromatin foci (SAHF) status, including the number of cells with fragments and the number of SAHF fragments in each cell. RESULTS: A higher TERC gene copy number was observed in cells from PSC patients compared to colitis and control group patients. It was also higher in the colitis than in the control group. Significantly more cells in the senescent state and more fragmentation in each cell were observed in the PSC group compared to colitis and control groups. CONCLUSION: The TERC gene copy number and the number of cells in the senescent state were increased in PSC patients compared to the colitis and control groups. These findings are probably related to the genetic instability parameters that reflect the higher tendency of this patient group to develop malignancies.

False negative fecal occult blood test may be associated with increased mortality from colorectal cancer.

BACKGROUND: Fecal Occult Blood Test (FOBT) is an accepted screening test for colorectal cancer (CRC). It has been shown to decrease mortality by up to 30%. The outcome of screening failures has not been adequately studied. AIMS: The purpose of this study was to assess the outcome of patients who were diagnosed with CRC after a false negative FOBT. METHODS: We identified all consecutive CRCs from pathology reports between 2005 and 2010. Patients were divided according to their FOBT result. Those who became positive were compared to patients who remained negative. RESULTS: Altogether 401 CRCs were identified. Of those, 202 never performed a FOBT. At least one negative FOBT was performed by 133 individuals (67%). Of these, 76 remained negative (false negatives, FN) and 57 became positive (positive conversion, PC, controls). The prevalence of metastatic disease was threefold higher among the FNs as compared to the PC group (16 [22.2%] vs. 4 [7.5%], P=0.022). All-cause mortality was also significantly higher among FNs versus PCs (24 [31.6%] vs. 5 [8.8%], P=0.001); in Cox regression analysis of survival (covariates: FNs vs. PC, gender, age, medications and co-morbidities) FNs had increased mortality compared to the PC (HR 2.929, P=0.033, CI 95% 1.092-7.858). No statistically significant difference was found regarding all primary end points when comparing the FN and the "No test" group. CONCLUSION: These data disclose a particular risk of FOBT as a screening test. A subgroup of patients with "false" negative tests may have increased morbidity and mortality. Efforts should be made to recognize and characterize this high-risk group.

Cannabis induces a clinical response in patients with Crohn's disease: a prospective placebo-controlled study.

BACKGROUND & AIMS: The marijuana plant Cannabis sativa has been reported to produce beneficial effects for patients with inflammatory bowel diseases, but this has not been investigated in controlled trials. We performed a prospective trial to determine whether cannabis can induce remission in patients with Crohn's disease. METHODS: We studied 21 patients (mean age, 40 ± 14 y; 13 men) with Crohn's Disease Activity Index (CDAI) scores greater than 200 who did not respond to therapy with steroids, immunomodulators, or anti-tumor necrosis factor-α agents. Patients were assigned randomly to groups given cannabis, twice daily, in the form of cigarettes containing 115 mg of Δ9-tetrahydrocannabinol (THC) or placebo containing cannabis flowers from which the THC had been extracted. Disease activity and laboratory tests were assessed during 8 weeks of treatment and 2 weeks thereafter. RESULTS: Complete remission (CDAI score, <150) was achieved by 5 of 11 subjects in the cannabis group (45%) and 1 of 10 in the placebo group (10%; P = .43). A clinical response (decrease in CDAI score of >100) was observed in 10 of 11 subjects in the cannabis group (90%; from 330 ± 105 to 152 ± 109) and 4 of 10 in the placebo group (40%; from 373 ± 94 to 306 ± 143; P = .028). Three patients in the cannabis group were weaned from steroid dependency. Subjects receiving cannabis reported improved appetite and sleep, with no significant side effects. CONCLUSIONS: Although the primary end point of the study (induction of remission) was not achieved, a short course (8 weeks) of THC-rich cannabis produced significant clinical, steroid-free benefits to 10 of 11 patients with active Crohn's disease, compared with placebo, without side effects. Further studies, with larger patient groups and a nonsmoking mode of intake, are warranted. ClinicalTrials.gov, NCT01040910.