Cholecystectomy and Biliary Sphincterotomy Increase Fecal Bile Loss and Improve Lipid Profile in Dyslipidemia.

BACKGROUND AND AIMS: Bile is the only significant pathway for cholesterol elimination. Cholecystectomy (CS) increases fecal bile acid loss, and endoscopic biliary sphincterotomy (ES) is thought to have a similar effect. We speculated that a combined effect of ES + CS would further enhance fecal bile acid loss, potentially causing lipid profile changes in these patients. METHODS: Fecal bile acids and sterols were determined using gas chromatography in cohorts of post-CS + ES, post-CS and in healthy controls. The effect of ES + CS on blood lipid profile was assessed retrospectively in a single-center cohort of post-CS + ES patients, using a computerized database. Parameters of interest included demographics, medical history, and lipid profiles. RESULTS: Fecal primary bile acid concentrations were increased after CS + ES compared to CS and controls (cholic acid [CA] 1.4 ng/mg vs. 0.26 ng/mg, p = 0.02 vs. 0.23 ng/mg, p = 0.004, chenodeoxycholic acid [CDCA] 1.92 ng/mg vs. 0.39 ng/mg, p = 0.02 vs. 0.23 ng/mg, p = 0.01, respectively). Fecal cholesterol excretion was similar in all three groups. Baseline serum lipid profile and subsequent changes following CS + ES were correlated. In patients with baseline hypercholesterolemia (total cholesterol (TC) > 200 mg/dl), TC levels decreased by 28.5 mg/dl, and LDL levels decreased by 21.5 mg/dl. The effect was more pronounced in those with TC > 200 mg/dl, despite of statin intake. In patients with hypertriglyceridemia [triglycerides (TG) > 200 mg/dl], TG decreased by 67.8 mg/dl following ES + CS. Among patients without dyslipidemia or dyslipidemia with adequate response to statins, the effect of ES + CS on lipid profile was minor. CONCLUSIONS: Fecal bile acid loss increases following CS + ES. The effect on blood lipid profile depends on baseline TC and TG levels. Lipid profile is improved in dyslipidemic patients, while the impact of CS + ES is minimal on the normolipemic population.

Diabetes Mellitus and Age are Risk Factors of Interval Colon Cancer: A Case-Control Study.

BACKGROUND AND AIMS: Interval colorectal cancer (CRC) is largely related to a poor endoscopic performance or different biology in the development of the polyp. However, patient-related factors were less investigated for their association with interval cancer. We thus evaluated tumor and patient characteristics as predictors of interval cancer in a population from Israel. METHODS: In this retrospective study, patients that were diagnosed with colon cancer in our institution and had 2 colonoscopies were included. Demographic parameters and tumor characteristics were compared between 84 cases with interval cancer, occurring 1-10 years after a negative colonoscopy, and 983 patients with primary CRC. In addition, patient-related features, including diabetes and diverticulosis, were compared between 51 patients with interval cancer after negative colonoscopy and 255 controls with no cancer and a previous negative colonoscopy. RESULTS: Compared to "positive" controls with primary cancer, patients with interval cancer were older (age 71.3 vs. 67.6, p = 0.003), had proximal tumor location (57 vs. 34%, p < 0.001) and non-advanced (0-2) tumor staging (78.5 vs. 64.8%, p = 0.014). Compared with -"negative" healthy controls, cases with interval cancer had only higher prevalence of diabetes (31 vs. 15%, p = 0.002). No significant differences were seen between patients with interval cancer occurring < 3 years and after 3-10 years. CONCLUSIONS: Patients with Interval cancer tend to be older and have diabetes. These patient groups should be more carefully or more frequently screened for pre-malignant lesions.

A novel gallbladder umbrella stent (the Shai™ Stent) for prevention of stone migration and impaction: results on feasibility and short-term safety in a porcine model.

BACKGROUND AND AIMS: Cholelithiasis is the most common biliary tract disorder. Surgery is the treatment of choice for symptomatic gallstones. Aims of this study were to investigate the feasibility and short-term safety of a new endoscopic procedure with a specially designed Nitinol gallbladder stent for blockage of gallstone migration, the Shai™ Stent. The Shai stent is designed to enable free bile flow, which will be supposed to prevent recurrent attacks. METHODS: The Shai™ Stent was inserted into the gallbladder during a standard ERCP procedure using a conventional metal stent delivery system. The aim of the present study was to investigate the feasibility and safety of insertion and deployment and removal of the stent into the gallbladder of pigs. In addition, the short-term safety of the stent was evaluated. RESULTS: Fifteen stents were placed in the gallbladder of 15 pigs. Mean procedure time was 25 min (15-37). The maximum follow-up before sacrifice was 42 days. The stent in 1 pig had migrated at the 42 days follow-up but there were no macroscopic changes in its gallbladder or other organs. The stent remained in place in the remaining 12 pigs at autopsy, and the gallbladder and bile ducts were macroscopically normal. Stent removal was easily done in two pigs immediately after placement. CONCLUSIONS: Correct placement and removal of the Shai™ Stent in the gallbladder is safe and feasible in pigs. Further clinical trials are warranted to confirm these results and to effectively evaluate the capability of this stent as an innovative biotechnology to block gallstones from migration and impaction.

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.

Pouch Inflammation Is Associated With a Decrease in Specific Bacterial Taxa.

BACKGROUND & AIMS: Pouchitis is a common long-term complication in patients with ulcerative colitis (UC) undergoing proctocolectomy with ileal pouch-anal anastomosis. Because the inflammation occurs in a previously normal small bowel, studies of this process might provide information about the development of Crohn's disease. Little is known about the intestinal microbiome of patients with pouchitis. We investigated whether specific bacterial populations correlate with the pouch disease phenotype and inflammatory activity. METHODS: We performed a prospective study of patients with UC who underwent pouch surgery (N = 131) from 1981 through 2012 and were followed at Tel Aviv Medical Center. Patients were assigned to groups based on their degree and type of pouch inflammation. Patients with familial adenomatous polyposis after pouch surgery (n = 9), individuals with intact colons undergoing surveillance colonoscopy (n = 10), and patients with UC who did not undergo surgery (n = 9) served as controls. We collected demographic and disease activity data (based on the Pouchitis Disease Activity Index) and measured levels of C-reactive protein. Fecal samples were collected, levels of calprotectin were measured, and microbiota were analyzed by 16S ribosomal RNA gene amplicon pyrosequencing. RESULTS: Increased proportions of the Fusobacteriaceae family correlated with increased disease activity and levels of C-reactive protein in patients with UC who underwent pouch surgery. In contrast, proportions of Faecalibacterium were reduced in patients with pouchitis vs controls; there was a negative correlation between proportion of Faecalibacterium and level of C-reactive protein. There was an association between antibiotic treatment, but not biologic or immunomodulatory therapy, with reduced proportions of 11 genera and with increased proportions of Enterococcus and Enterobacteriaceae. CONCLUSIONS: Reductions in protective bacteria and increases in inflammatory bacteria are associated with pouch inflammation in patients with UC who underwent pouch surgery. The finding that antibiotics exacerbate dysbiosis indicates that these drugs might not provide long-term benefit for patients with pouchitis. Additional studies of this form of dysbiosis could provide information about the pathogenesis of Crohn's disease.

Telomere Dysfunction in Nonalcoholic Fatty Liver Disease and Cryptogenic Cirrhosis.

Nonalcoholic fatty liver disease (NAFLD) and cryptogenic cirrhosis (CC) are considered preneoplastic conditions that might progress to hepatocellular carcinoma. We evaluated parameters of telomere dysfunction in these patient groups to study the correlation between telomere length and the progression of NAFLD. We analyzed peripheral lymphocytes from 22 patients with NAFLD, 20 patients with CC, and 20 healthy, age-matched controls. Telomere length was analyzed using quantitative fluorescence in situ hybridization, and cellular senescence was evaluated by the percentage of cells with senescence-associated heterochromatin foci. The expression of telomerase reverse transcriptase (hTERT) mRNA was measured using polymerase chain reaction, and telomere capture (TC) was assessed with 2 Cytocell probes, 15qter and 13qter. Shorter telomere length and increased cellular senescence was demonstrated in patients with NAFLD, compared to the CC patients and healthy controls. While hTERT mRNA was significantly decreased, TC was increased in CC patients, compared to the NAFLD group and healthy individuals. Thus, there is a correlation between hTERT mRNA expression and telomere length in patients with NAFLD, which might be related to associated metabolic disorders and the risk of malignant transformation. Patients with CC, on the contrary, elongate their telomeres through the TC mechanism.

Genetic and electrophysiological characteristics of recurrent acute pancreatitis.

OBJECTIVES: The aim was to present the workup of patients with acute recurrent pancreatitis (ARP) for genetic analysis and electrophysiological testing. METHODS: Patients with ARP with unknown etiology were referred for genetic testing and evaluation of cystic fibrosis transmembrane conductor regulator (CFTR) function by nasal potential difference (NPD) testing. RESULTS: A total of 67 patients were evaluated. The mean age was 23 ±â€Š17 years (median 17.0 years, range 1.5-72 years); 90% were Jewish and 10% Arab. Ten (15%) patients carried PRSS1 gene mutation (K23R(7), R122H(2), and D21A(1)). One patient had K172E/- (chymotrypsin C [CTRC]) mutation, 1 had I42M (serine protease inhibitor Kazal type 1 [SPINK1])/V235I (CTRC) together with ΔF508/5T, 1 patient had R67H (SPINK1)/V235I (CTRC), and 1 patient had V235I (CTRC)/-. Ten of 67 (15%) patients submitted for CFTR gene testing carried mutations (ΔF508/L997F, ΔF508/5T(11TG), W1282/5T(12TG), W1282X/Y1014C, ΔF508/R31C, R117H/-, R117H/Y1014C, D1152H/-, 5T(11TG)/-, and L997F/-). Fifty-four (80%) patients underwent sweat testing. Of these, 5 had sweat chloride ≥60 mEq/L, and 22 patients had sweat chloride from 40 to 60 mEq/L. Of the 56 (83%) patients had nasal potential difference testing, 4 (6%) with abnormal results. CONCLUSIONS: One-third (34%) of patients with ARP carry mutations for hereditary pancreatitis including rare mutations (K23R), and 12.5% have evidence of cftr mutations and 10% had CFTR dysfunction underscoring the importance of genetic and functional workup of these patients.

Soluble Syndecan-1 Levels Are Elevated in Patients with Inflammatory Bowel Disease.

BACKGROUND: Syndecan-1 plays a central role in maintaining normal intestinal barrier function. Shedding of syndecan-1, reflected by soluble syndecan-1 serum concentrations, is highly regulated by inflammation. AIM: To determine soluble syndecan-1 levels in inflammatory bowel disease patients and its relationship with other inflammatory markers, disease activity, and medical treatment. METHODS: Cross-sectional, pilot study in which serum concentrations of soluble syndecan-1 were analyzed by ELISA in a cohort of 41 inflammatory bowel disease patients (22 Crohn's disease, 19 ulcerative colitis) and 16 healthy controls. Disease activity was estimated by the Crohn's disease activity index, partial Mayo score, and C-reactive protein. RESULTS: Soluble syndecan-1 levels were significantly higher in inflammatory bowel disease patients compared to healthy controls (29.5 ± 13.4 vs. 21.1 ± 10.4 ng/ml, respectively, P = 0.03). Soluble syndecan-1 displayed a reliable ability to discriminate inflammatory bowel disease patients from healthy controls with a sensitivity of 95 %, specificity of 50 %, and positive predictive value of 83 %. Patients treated with anti-inflammatory medications demonstrated significantly lower soluble syndecan-1 levels compared to untreated patients (26.45 ± 9.75 vs. 38 ± 18.43 ng/ml, respectively, P = 0.008). CONCLUSIONS: Our results suggest that soluble syndecan-1 is potentially a novel diagnostic marker in the management of inflammatory bowel disease patients. Its applicability as a surrogate, prognostic biomarker remains to be determined.

[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.

The fatty acid-bile acid conjugate Aramchol reduces liver fat content in patients with nonalcoholic fatty liver disease.

BACKGROUND & AIMS: We investigated the effects of the fatty acid-bile acid conjugate 3ß-arachidyl-amido, 7α-12α-dihydroxy, 5ß-cholan-24-oic acid (Aramchol; Trima Israel Pharmaceutical Products Ltd, Maabarot, Israel) in a phase 2 trial of patients with nonalcoholic fatty liver disease (NAFLD). METHODS: We performed a randomized, double-blind, placebo-controlled trial of 60 patients with biopsy-confirmed NAFLD (6 with nonalcoholic steatohepatitis) at 10 centers in Israel. Patients were given Aramchol (100 or 300 mg) or placebo once daily for 3 months (n = 20/group). The main end point was the difference between groups in the change in liver fat content according to magnetic resonance spectroscopy. The secondary end points focused on the differences between groups in alterations of liver enzyme levels, levels of adiponectin, homeostasis model assessment scores, and endothelial function. RESULTS: No serious or drug-related adverse events were observed in the 58 patients who completed the study. Over 3 months, liver fat content decreased by 12.57% ± 22.14% in patients given 300 mg/day Aramchol, but increased by 6.39% ± 36.27% in the placebo group (P = .02 for the difference between groups, adjusted for age, sex, and body mass index). Liver fat content decreased in the 100-mg Aramchol group, by 2.89% ± 28.22%, but this change was nonsignificant (P = .35), indicating a dose-response relationship (P for trend = .01). Groups given Aramchol had nonsignificant improvements over time in endothelial function and levels of alanine aminotransferase and adiponectin, but homeostasis model assessment scores did not change. The appropriateness of a single daily dose was confirmed by pharmacokinetic analysis. CONCLUSIONS: Three months' administration of the fatty acid-bile acid conjugate Aramchol is safe, tolerable, and significantly reduces liver fat content in patients with NAFLD. The reduction in liver fat content occurred in a dose-dependent manner and was associated with a trend of metabolic improvements, indicating that Aramchol might be used for the treatment of fatty liver disease. ClinicalTrials.gov number: NCT01094158.

Gastric microbiota is altered in oesophagitis and Barrett's oesophagus and further modified by proton pump inhibitors.

Gastro-oesophageal reflux can cause inflammation, metaplasia, dysplasia and cancer of the oesophagus. Despite the increased use of proton pump inhibitors (PPIs) to treat reflux, the incidence of oesophageal adenocarcinoma has increased rapidly in Europe and in the United States in the last 25 years. The reasons for this increase remain unclear. In this study, we aimed to determine whether the microbiota of the gastric refluxate and oesophageal biopsies differs between patients with heartburn and normal-appearing oesophageal mucosa versus patients with abnormal oesophageal mucosa [oesophagitis or Barrett's oesophagus (BE)] and to elucidate the effect of PPIs on the bacterial communities using 16S rRNA gene pyrosequencing. Significant differences in the composition of gastric fluid bacteria were found between patients with heartburn and normal oesophageal tissue versus patients with oesophagitis or BE, but in the oesophagus-associated microbiota differences were relatively modest. Notably, increased levels of Enterobacteriaceae were observed in the gastric fluid of oesophagitis and BE patients. In addition, treatment with PPIs had dramatic effects on microbial communities both in the gastric fluids and the oesophageal tissue. In conclusion, gastric fluid microbiota is modified in patients with oesophagitis and BE compared with heartburn patients with normal biopsies. Furthermore, PPI treatment markedly alters gastric and oesophageal microbial populations. Determining whether the changes in bacterial composition caused by PPIs are beneficial or harmful will require further investigation.

Cannabis for inflammatory bowel disease.

The marijuana plant Cannabis sativa has been used for centuries as a treatment for a variety of ailments. It contains over 60 different cannabinoid compounds. Studies have revealed that the endocannabinoid system is involved in almost all major immune events. Cannabinoids may, therefore, be beneficial in inflammatory disorders. In murine colitis, cannabinoids decrease histologic and microscopic inflammation. In humans, cannabis has been used to treat a plethora of gastrointestinal problems, including anorexia, emesis, abdominal pain, diarrhea, and diabetic gastroparesis. Despite anecdotal reports on medical cannabis in inflammatory bowel disease (IBD), there are few controlled studies. In an observational study in 30 patients with Crohn's disease (CD), we found that medical cannabis was associated with improvement in disease activity and reduction in the use of other medications. In a more recent placebo-controlled study in 21 chronic CD patients, we showed a decrease in the CD activity index >100 in 10 of 11 subjects on cannabis compared to 4 of 10 on placebo. Complete remission was achieved in 5 of 11 subjects in the cannabis group and 1 of 10 in the placebo group. Yet, in an additional study, low-dose cannabidiol did not have an effect on CD activity. In summary, evidence is gathering that manipulating the endocannabinoid system can have beneficial effects in IBD, but further research is required to declare cannabinoids a medicine. We need to establish the specific cannabinoids, as well as appropriate medical conditions, optimal dose, and mode of administration, to maximize the beneficial effects while avoiding any potential harmful effects of cannabinoid use.

Consecutive versus separate sessions of endoscopic ultrasound (EUS) and endoscopic retrograde cholangiopancreatography (ERCP) for symptomatic choledocholithiasis.

BACKGROUND: Common bile duct (CBD) stones are a potentially life-threatening medical condition. Patients with proven CBD stones should undergo stone extraction. The aim of this study was to evaluate whether performing endoscopic ultrasound (EUS) and endoscopic retrograde cholangiopancreatography (ERCP) for symptomatic CBD stones in a single session reduces complications related to postponing treatment due to separate EUS and ERCP sessions, and to assess the safety in both options. METHODS: A total of 151 patients with EUS-proven CBD stones, with subsequent ERCP, treated in our department between January 2005 and December 2011 were included. Complications related to the procedures or sedation and complications due to the CBD stones when EUS and ERCP were not performed in a single session were assessed and compared to complications when the two procedures were performed in one session. RESULTS: In total, 149 patients of the 151 (98.7 %) had a successful ERCP. Four (5 %) patients in the separate-session group (B) had a major complication compared to none in the single-session group (A) (p > 0.05). Group B received 14 % more midazolam during ERCP than group A (p < 0.05). No sedation-related complications were noted in either group. Eleven of the 80 patients in group B (13.8 %) experienced complications while waiting for ERCP compared to none in group A (p = 0.001, OR = 2.17, CI = 1.06-4. CONCLUSIONS: EUS and ERCP done in a single session proved to be safe, with no increase in sedation- or procedure-related complications. Postponing treatment for symptomatic CBD stones exposes the patient to biliary complications, especially cholangitis.

Effects of age and cholecystectomy on common bile duct diameter as measured by endoscopic ultrasonography.

BACKGROUND AND AIM: Increased common bile duct (CBD) diameter has been attributed to aging and previous cholecystectomy. These relationships are, however, controversial and based mainly on old studies and methodologies. Our objective is to evaluate the relationship between age, cholecystectomy, and other clinical factors and CBD diameter, as measured by endoscopic ultrasound (EUS). METHODS: We carried out a retrospective cohort study including patients who underwent EUS in our institution. Patients with an obstructing lesion of the bile ducts, previous sphincter manipulation, or insufficient data were excluded. CBD diameter was measured as a routine part of the examination, in the most distal extrapancreatic portion, between its two exterior margins. The patients were divided into five age groups. The mean CBD diameter in each group was calculated and compared with the other groups. Effects of cholecystectomy, gender, time from operation, and elevated liver enzymes were also evaluated. RESULTS: Six hundred forty-seven patients were included in the study (66% women). Twenty-three percent were postcholecystectomy. There was no difference between the first three groups regarding CBD diameter, but it was significantly wider in groups 4 and 5 (p < 0.001). In all age groups, the postcholecystectomy patients had significantly wider CBD than those with an intact gallbladder (in all groups, p < 0.01). CONCLUSIONS: This EUS study confirms that the CBD dilates significantly after the age of 70 years, but even in the most elderly patients, with an intact gallbladder, the normal CBD does not exceed 7.6 mm, thus a wider CBD warrants further investigation. The single additional factor contributing to dilatation of the CBD was cholecystectomy. A linear regression equation is proposed for the prediction of CBD diameter.

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.

Treatment of Crohn's disease with cannabis: an observational study.

BACKGROUND: The marijuana plant cannabis is known to have therapeutic effects, including improvement of inflammatory processes. However, no report of patients using cannabis for Crohn's disease (CD) was ever published. OBJECTIVES: To describe the effects of cannabis use in patients suffering from CD. METHODS: In this retrospective observational study we examined disease activity, use of medication, need for surgery, and hospitalization before and after cannabis use in 30 patients (26 males) with CD. Disease activity was assessed by the Harvey Bradshaw index for Crohn's disease. RESULTS: Of the 30 patients 21 improved significantly after treatment with cannabis. The average Harvey Bradshaw index improved from 14 +/- 6.7 to 7 +/- 4.7 (P < 0.001). The need for other medication was significantly reduced. Fifteen of the patients had 19 surgeries during an average period of 9 years before cannabis use, but only 2 required surgery during an average period of 3 years of cannabis use. CONCLUSIONS: This is the first report of cannabis use in Crohn's disease in humans. The results indicate that cannabis may have a positive effect on disease activity, as reflected by reduction in disease activity index and in the need for other drugs and surgery. Prospective placebo-controlled studies are warranted to fully evaluate the efficacy and side effects of cannabis in CD.

Oral CBD-rich Cannabis Induces Clinical but Not Endoscopic Response in Patients with Crohn's Disease, a Randomised Controlled Trial.

AIMS: Despite reports that medical cannabis improves symptoms in Crohn's disease [CD], controlled studies evaluating disease response are lacking. This study assessed the effect of cannabidiol [CBD]-rich cannabis oil for induction of remission in CD. METHODS: In a double-blind, randomised, placebo-controlled, single-centre trial, patients received orally either cannabis oil containing160/40 mg/ml cannabidiol/tetrahydrocannabinol [CBD/THC] or placebo for 8 weeks. Disease parameters, including the CD activity index [CDAI], and simple endoscopic score for CD [SES-CD], were assessed before and after treatment. In a subgroup of patients, blood samples were collected for CBD and THC plasma levels. RESULTS: The study included 56 patients, age 34.5 ± 11 years, men/women 30/26 [54/46%],30 in cannabis and 26 in placebo groups. CDAI at recruitment and after 8 weeks was 282 (interquartile range [IQR] 243-342) and 166 [IQR 82-226], and 264 [IQR 234-320] and 237 [IQR 121-271] [p <0.05] in the cannabis and placebo groups, respectively. Median quality of life [QOL] score improved from 74 for both groups at baseline to 91 [IQR 85-102] and 75 [IQR 69-88] after 8 weeks in the cannabis and placebo groups, respectively [p = 0.004]. SES-CD was 10 [IQR 7-14] and 11 [IQR7-14], and 7 [4-14] and 8 [IQR 4-12] [p = 0.75] before and after treatment, in the cannabis and placebo groups, respectively. Inflammatory markers (C-reactive protein [CRP], calprotectin) remained unchanged. CONCLUSIONS: Eight weeks of CBD-rich cannabis treatment induced significant clinical and QOL improvement without significant changes in inflammatory parameters or endoscopic scores. The oral CBD-rich cannabis extract was well absorbed. Until further studies are available, cannabis treatment in Crohn's disease should be used only in the context of clinical trials.

Risk of metachronous advanced lesions after resection of diminutive and small, non-advanced adenomas.

BACKGROUND AND AIMS: Current post-polypectomy surveillance interval guidelines do not discriminate between 1-2 diminutive (1-5mm) and small (6-9mm) non-advanced adenomas. This study compared the risk for metachronous advanced lesions in these groups. METHODS: Patients with 1-2 diminutive, non-advanced adenomas and no further advanced lesions, and patients with no polyps at baseline colonoscopy were retrospectively analyzed to determine the rate of metachronous advanced lesions. These were defined as the combined rate of colon cancer, advanced adenoma and ≥ 3 non-advanced adenomas at surveillance colonoscopy. Polyp size was measured either subjectively by the endoscopist or by pathology-based measurements. RESULTS: Among patients with diminutive (n = 395) and small polyps (n = 110), advanced lesions were found in 68 patients (17.2%) and 16 patients (14.5%), respectively (P = 0.53), during a mean follow-up of 4.3 ± 0.9 years. In contrast, advanced lesions were observed in 33 patients (6.6%) in the no polyp group (n = 505), significantly lower than diminutive (P = 0.000) and small polyp groups (P = 0.002), despite a mean follow-up duration of 6.1 ± 1.9 years. The rate of metachronous advanced lesions was also similar between patients with 1-3mm polyps (16%) versus 7-9mm polyps (15.8%). CONCLUSIONS: Our findings suggest that among patients who underwent polypectomy of up to 2 non-advanced adenomas, those with diminutive and small polyps have the same risk of metachronous advanced lesions; thus, supporting uniform recommendations for surveillance colonoscopy for these lesions.