Stepwise Algorithmic Approach to Endoscopic Removal of Biliary Partially Covered and Uncovered Self-Expanding Metal Stents.

Self-expanding metal stents play a crucial role in the management of patients with biliary obstruction. Endoscopic extraction of uncovered metal stents (UCMSs) and partially covered metal stents (PCMSs) could be challenging because of tissue ingrowth. No standardized technique can guarantee universal success. We present our technique and experience of endoscopic extraction of biliary stents in two patients with a UCMS and three patients with a PCMS. Three of the five patients had a previous failed attempt of stent extraction at an outside hospital. Overall, our composite success rate was 80% (4/5). The individual success rate was 100% (3/3) for PCMSs and 50% (1/2) for UCMSs. The stent-in-stent technique, in which a fully covered metal stent is placed through an existing UCMS/PCMS, was used in 60% (3/5) of the cases, with a success rate of 66.7% (2/3). We share our algorithmic approach to each case, with detailed emphasis on the technical aspects of the procedure.

Physician adherence to societal guidelines following colonoscopy with polypectomy.

BACKGROUND: Colorectal cancer is a significant cause of mortality and morbidity in western countries. Polypectomy reduces the incidence and mortality of colorectal cancer. Following polypectomy, recommendations regarding the frequency and duration of surveillance rely mostly on features of the resected polyps and are summarized in various gastroenterological societal guidelines. In this study, we aimed to delineate the accuracy of current post-polypectomy surveillance recommendations and to check whether active intervention would lead to an improvement in accuracy and consistency with societal guidelines. METHODS: We prospectively collected polypectomy reports over a 3-month period in 2 tertiary medical centers. We then performed an intervention that included: 1) presentation of results from 1st phase; 2) re-affirming the guidelines in a departmental meeting; 3) addition of a dedicated reporting form for post-polypectomy surveillance recommendations in the patients' electronic medical file. Finally, we conducted a second prospective collection of post-polypectomy recommendations, over a second 3-month period. RESULTS: Prior to the intervention, 76% of the colonoscopies with polypectomy had a recommendation for surveillance, compared to 85% after the intervention (P=0.003). Prior to the intervention, 65% of patients received a recommendation consistent with societal guidelines, compared with 78% after the intervention (P=0.001). CONCLUSION: Intervention, including re-affirmation of the current guidelines and creation of a dedicated reporting platform, significantly increases the number of follow-up recommendations after polypectomy and their consistency with societal guidelines.

Colon mucosal neoplasia referred for endoscopic mucosal resection: Recurrence of adenomas and prediction of submucosal invasion.

BACKGROUND: Endoscopic mucosal resection (EMR) is an effective and minimally invasive alternative to surgery for large polyps and laterally spreading lesions. Gross morphology and surface characteristics may help predict submucosal invasion of the lesion (SMIL) during endoscopic evaluation. This is one of the largest single-center studies reporting endoscopic mucosal resection for larger (≥ 20 mm) colorectal lesions in the United States. AIM: To determine the recurrence rate of adenomas and endoscopic features that may predict submucosal invasion of colonic mucosal neoplasia. METHODS: This is a retrospective cohort study of all the patients referred for endoscopic mucosal resection for lesions ≥ 20 mm, spanning a period from January 2013 to February 2017. The main outcome measure was identifying features that may predict submucosal invasion of mucosal lesions and predict recurrence of adenomas on follow-up surveillance colonoscopy performed at 4-6 mo. RESULTS: A total of 480 patients with 500 lesions were included in the study. The median age was 68 (Inter quantile range: 14) with 52% males. The most common lesion location was ascending colon (161; 32%). Paris classification 0-IIa (Flat elevation of mucosa - 316; 63.2%); Kudo Pit Pattern IIIs (192; 38%) and Granular surface morphology (260; 52%) were most prevalent. Submucosal invasion was present in 23 (4.6%) out of 500 lesions. The independent risk factors for SMIL were Kudo Pit Pattern IIIL + IV and V (Odds ratio: 4.5; P value < 0.004) and Paris classification 0-IIc (Odds ratio: 18.2; P value < 0.01). Out of 500, 354 post-endoscopic mucosal resection scars were examined at surveillance colonoscopy. Recurrence was noted in 21.8% (77 cases). CONCLUSION: There was overall low prevalence of SMIL in our study. Kudo pit pattern (IIIL + IV and V) and Paris classification 0-IIc were the only factors identified as an independent risk factor for submucosal invasion. The independent risk factor for recurrence was adenoma size (> 40 mm). Almost all recurrences (98.8%) were treated endoscopically.

The effect of colonoscopy on intraocular pressure: an observational prospective study.

PURPOSE: Colonoscopy is an endoscopic examination of the bowel. It requires insufflation of the large bowel lumen with gas which leads to intraabdominal hypertension (IAH). There is evidence suggesting that IAH positively correlates with intracranial pressure (ICP) and possibly with intraocular pressure (IOP). The aim of this study was to examine the effect of routine screening colonoscopy performed under sedation on the IOP in healthy individuals. PATIENTS AND METHODS: This was a prospective, single site, observational study. Healthy adults undergoing routine colonoscopy performed under sedation including propofol, fentanyl, and midazolam were recruited. Right eye IOP measurements were performed using Tonopen XL® in a left decubitus position at 5 time points during the procedure. Statistical analysis was performed using Student's t-test for paired samples. RESULTS: Twenty-three Caucasians were recruited. There are 14 males (60%) with a mean age of 60.4 ± 10.4 years (range 36-74). Colonoscopy was conducted under sedation and completed in 22 subjects. Mean baseline IOP was 19.9 ± 4.7 mmHg, 15.8 ± 4.8 mmHg immediately after sedation, 13.5 ± 2.3 mmHg when the colonoscope had reached the cecum, 15.4 ± 5.0 mmHg 5 min after colonoscopy beginning, and 16.5 ± 5.5 mmHg when located in the rectum. The IOP reduction during the procedure was statistically significant (P < 0.01). CONCLUSION: Routine colonoscopy performed under sedation using propofol, fentanyl, and midazolam does not increase the IOP in healthy adults.

Fecal microbiome signatures of pancreatic cancer patients.

Pancreatic cancer (PC) is a leading cause of cancer-related death in developed countries, and since most patients have incurable disease at the time of diagnosis, developing a screening method for early detection is of high priority. Due to its metabolic importance, alterations in pancreatic functions may affect the composition of the gut microbiota, potentially yielding biomarkers for PC. However, the usefulness of these biomarkers may be limited if they are specific for advanced stages of disease, which may involve comorbidities such as biliary obstruction or diabetes. In this study we analyzed the fecal microbiota of 30 patients with pancreatic adenocarcinoma, 6 patients with pre-cancerous lesions, 13 healthy subjects and 16 with non-alcoholic fatty liver disease, using amplicon sequencing of the bacterial 16S rRNA gene. Fourteen bacterial features discriminated between PC and controls, and several were shared with findings from a recent Chinese cohort. A Random Forest model based on the microbiota classified PC and control samples with an AUC of 82.5%. However, inter-subject variability was high, and only a small part of the PC-associated microbial signals were also observed in patients with pre-cancerous pancreatic lesions, implying that microbiome-based early detection of such lesions will be challenging.

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.

Telomere dysfunction in peripheral blood lymphocytes from patients with primary sclerosing cholangitis and inflammatory bowel disease.

BACKGROUND AND AIMS: Primary sclerosing cholangitis and inflammatory bowel disease are two associated, chronic inflammatory, pre-malignant conditions. We hypothesized that patients with these disorders may harbour telomere dysfunction as a marker of chromosomal instability. The aim of our study was to compare parameters of the telomere-telomerase system in these cohorts. METHODS: In this prospective study, peripheral blood was withdrawn from patients with primary sclerosing cholangitis (N=20), inflammatory bowel disease (N=20) and healthy controls (N=20), and lymphocytes were isolated. Telomere length was quantified as a function of the signal intensity and telomere number. Random aneuploidy and telomere capture were determined by fluorescence in situ hybridization technique with specific probes. RESULTS: Patients with inflammatory bowel disease had higher measures of intestinal disease activity than patients with primary sclerosing cholangitis. Despite this, shorter telomere length and telomere aggregates, especially the fusion of 2-5 telomeres, were observed at significantly higher rate in patients with primary sclerosing cholangitis relative to inflammatory bowel disease or healthy controls. Rates of aneuploidy and telomere capture were higher in the two probes in both diseases compared to controls (p<0.001). CONCLUSION: Dysfunction of telomeres was demonstrated in primary sclerosing cholangitis patients more than inflammatory bowel disease and healthy controls patients, which attests to genetic instability and immunosenescence. TRIAL REGISTRATION NUMBER: NCT02247622.

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.

Prognosis of primary sclerosing cholangitis in israel is independent of coexisting inflammatory bowel Disease.

BACKGROUND AND AIMS: Primary sclerosing cholangitis (PSC) is a rare chronic progressive cholestatic disorder. We assessed its characteristics and natural history in Israel and compared its outcome with respect to coexisting inflammatory bowel disease (IBD). METHODS: Data on characteristics, course and outcome were retrospectively retrieved on patients diagnosed with PSC from five large Israeli medical centers between 1988 and 2012. Patients with isolated PSC were compared with those with coexisting IBD to identify predictors of outcome. RESULTS: Of 141 patients (56% males) with confirmed PSC, 98 (69.5%) had coexisting IBD. The average age at presentation was 38.8 ± 15.4 years and duration of follow-up was 7.93 ± 6.26 years. The crude estimated point prevalence was 4 cases per 105 persons. Demographics and clinical characteristics were similar among all patients except for symptoms at diagnosis (which were more prevalent among PSC­IBD patients) and utilization of multiple diagnostic modalities (which was more prevalent among isolated-PSC patients). More than one-third of the entire cohort had cirrhosis. A total of 15 patients (10.6%) died and 19 patients (13.5%) developed malignancy during follow-up. Nine patients (6.3%) underwent liver transplantation. Mean survival for the entire cohort was 26.3 ± 1.4 years and mean transplant-free survival was 23.5 ± 1.6 years. Cox proportional hazard regression for transplantation or death revealed two independent risk factors: cirrhosis and malignancy [hazard ratio 4.25 (p = 0.004) and 2.58 (p = 0.046), respectively]. CONCLUSIONS: Survival rate of PSC patients in Israel is longer than reported rates worldwide and is independent of coexisting IBD.

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.

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.

Effect of ezetimibe on the prevalence of cholelithiasis.

AIM: To investigate the prevalence of cholelithiasis among patients treated with ezetimibe. METHODS: A retrospective, case-control study based on computerized medical records from patients of the Clalit Health Services, Sharon-Shomron region, from 2000 to 2009. Patients 20-85 years of age, who had been treated with ezetimibe and statins or statins only for at least 6 mo, and who had an abdominal ultrasound were included in the study. Collected data included age, gender, ezetimibe treatment duration, presence of hypothyroidism or diabetes, and existence of cholelithiasis as determined by ultrasound. Excluded were subjects after gallbladder resection, with hemolysis, myeloproliferative or inflammatory bowel diseases, and those treated with ursodeoxycholic acid and fibrates. Patients treated with statins and ezetimibe (study group) were compared to patients treated with statins only (control group). RESULTS: The study group included 25 patients and the control group 168. All patients in the study were treated with statins. The study group included 13 males (52%) and 12 females (48%), the control group 76 males (45%) and 92 (55%) females (P = 0.544). The groups did not differ in age (mean age: 68 ± 8 years, range 53-85 years vs mean age: 71 ± 8 years, range 51-85 years; P = 0.153) or in the rate of diabetic and hypothyroid patients [11 (44%) vs 57 (33%), P = 0.347 in the study group and 5 (20%) vs 23 (14%), P = 0.449 in the control group, respectively]. Patients in the study group were treated with ezetimibe for an average of 798 ± 379 d. Cholelithiasis was found in 4 (16%) patients in the study group and in 33 (20%) patients in the control group (P = 0.666). CONCLUSION: Ezetimibe does not appear to influence the prevalence of gallstones.