Oral anticoagulants in fragile patients with percutaneous endoscopic gastrostomy and atrial fibrillation: the ORIGAMI pilot investigation.

BACKGROUND: Extensive data support the superior safety without any trade-off in efficacy of direct oral anticoagulants (DOACs) compared to vitamin K antagonists (VKA) in patients with nonvalvular atrial fibrillation, deep venous thrombosis or pulmonary embolism. Whether DOACs may be successfully used to treat complex and fragile patients with percutaneous endoscopic gastrostomy (PEG) remains to be proven. The purpose of this pilot study was to evaluate the feasibility, anticoagulant effect, and preliminary safety/efficacy profile of edoxaban administered via PEG in patients with an indication for long-term oral anticoagulation. METHODS: In this prospective, single-arm, pilot study, 12 patients with PEG and guideline-recommended indication for anticoagulation for nonvalvular atrial fibrillation were prospectively enrolled. Crushed edoxaban at approved doses was administered via PEG. Quantitative measures of edoxaban's antifactor Xa activity were performed at steady state. Thromboembolic and bleeding events were assessed at one-month follow-up. RESULTS: Steady state edoxaban plasma levels were at therapeutic range in all patients; mean plasma concentration was 208.5 (±78.6) ng/mL. At one month follow-up, none had suffered a thromboembolic event; one developed minor bleeding, and one died from non-cardiovascular death, owing to sudden worsening of a pre-existing underlying severe condition. CONCLUSIONS: In this pilot investigation, we report for the first time that crushed edoxaban, administered at approved doses through PEG in fragile and complex patients, is feasible, results in therapeutic edoxaban concentrations, and is apparently effective and safe.

ACE I allele is associated with more severe portal hypertension in patients with liver cirrhosis: A pilot study.

BACKGROUND: In liver cirrhosis, the renin-angiotensin-aldosterone system is involved in the pathogenesis of portal hypertension. Its effector, angiotensin II, is generated by angiotensin-converting enzyme (ACE). Serum ACE levels are affected by I/D polymorphism of its gene, with alleles I and D being associated, respectively, with lesser and greater activity of the enzyme. In cirrhotic patients carrying the ACE I allele, an increased risk for gastro-oesophageal varices was observed. AIM: The aim of our study was to evaluate whether ACE I/D polymorphism influenced portal pressure. METHODS: Fifty-one consecutive cirrhotic patients were divided based on ACE genotype (DD, ID, and II). Kidney and liver function tests, upper endoscopy, and hepatic venous pressure gradient measurement (HVPG) were performed in all patients. RESULTS: The presence of the ACE I allele was associated with a higher HVPG value (18.7±6.4 vs 10.3±6.3mmHg; P<.001), higher frequency of large gastrooesophageal varices (59.3% vs 25.0%; P<.05), and higher frequency of variceal bleeding (63.0% vs 29.2%; P<.05). No significant differences were found between patients with and those without the ACE I allele regarding Child-Pugh score, MELD score, ascites, and hepatic encephalopathy. CONCLUSION: ACE I/D polymorphism seems to influence the severity of portal hypertension and the risk of variceal bleeding in liver cirrhosis, regardless of the severity of liver disease.

The Role of Colonoscopy in the Diverticular Disease.

Colonic diverticula are one of the most frequent conditions found during the endoscopic examination of the lower digestive tract, interestingly in >70% of people after 80 years old. Of them, only a few percentage develop complications such as acute diverticulitis or diverticular bleeding. Up to now, colonoscopy represents the most important diagnostic and therapeutic tool on the hands of the clinicians. On the basis of this the need for a standardized and reproducible approach is now emerging. This short review article is tasked to point out some open issues concerning the role of colonoscopy in diverticular disease.

Nutrient infusion bypassing duodenum-jejunum improves insulin sensitivity in glucose-tolerant and diabetic obese subjects.

The mechanisms of type 2 diabetes remission after bariatric surgery is still not fully elucidated. In the present study, we tried to simulate the Roux-en-Y gastric bypass with a canonical or longer biliary limb by infusing a liquid formula diet into different intestinal sections. Nutrients (Nutrison Energy) were infused into mid- or proximal jejunum and duodenum during three successive days in 10 diabetic and 10 normal glucose-tolerant subjects. Plasma glucose, insulin, C-peptide, glucagon, incretins, and nonesterified fatty acids (NEFA) were measured before and up to 360 min following. Glucose rate of appearance (Ra) and insulin sensitivity (SI), secretion rate (ISR), and clearance were assessed by mathematical models. SI increased when nutrients were delivered in mid-jejunum vs. duodenum (SI × 104 min⁻¹·pM⁻¹: 1.11 ± 0.44 vs. 0.62 ± 0.22, P < 0.015, in controls and 0.79 ± 0.34 vs. 0.40 ± 0.20, P < 0.05, in diabetic subjects), whereas glucose Ra was not affected. In controls, Sensitivity of NEFA production was doubled in mid-jejunum vs. duodenum (2.80 ± 1.36 vs. 1.13 ± 0.78 × 106, P < 0.005) and insulin clearance increased in mid-jejunum vs. duodenum (2.05 ± 1.05 vs. 1.09 ± 0.38 l/min, P < 0.03). Bypass of duodenum and proximal jejunum by nutrients enhances insulin sensitivity, inhibits lipolysis, and increases insulin clearance. These results may further our knowledge of the effects of bariatric surgery on both insulin resistance and diabetes.

Polyethylene glycol plus simethicone in small-bowel preparation for capsule endoscopy.

BACKGROUND: Small-bowel contents can hamper the quality of video-capsule endoscopy (VCE). No standardized protocol has been proposed and overnight fasting remains the proposed preparation for VCE. AIMS: The aim was to evaluate the effects of 2 regimens of bowel preparation on small intestine cleansing, diagnostic yield and capsule transit times. METHODS: This is a prospective, randomized, blinded, and controlled study. Sixty patients referred for VCE were randomized into 2 groups. Group A ingested 2l of a polyethylene glycol and simethicone solution 16h before VCE. Group B were instructed to consume a fibre-free diet and allowed to consume clear liquids the day before VCE. The small-bowel cleansing was graded as "complete" if the entire wall was assessable, "incomplete" if more than 50% of the wall was visible, and "insufficient" if less than 50% of the wall was visible. RESULTS: In group A, a "complete", "incomplete" and "insufficient" small-bowel cleansing was achieved in 42%, 39% and 19% of cases respectively. In group B, a "complete", "incomplete" and "insufficient" small-bowel cleansing was achieved in 43%, 33% and 24% of cases respectively. No significant differences were observed between the two groups, regarding small-bowel cleansing level (p=0.65). No differences were also observed in the diagnostic yield (48.2%, 13.8% and 38% vs 65.5%, 6.9% and 27.6% of positive, suspicious and no findings respectively, in groups A and B [p=0.39]) and small-bowel transit times (mean 288min and 299 min in groups A and B respectively [p=0.70]). CONCLUSIONS: The results of the present study do not support the use of 2l of a polyethylene glycol and simethicone solution before VCE.

Capsule enteroscopy vs. other diagnostic procedures in diagnosing obscure gastrointestinal bleeding: a cost-effectiveness study.

BACKGROUND: Capsule enteroscopy is considered the gold standard for evaluating patients with obscure gastrointestinal bleeding. The costs of capsule enteroscopy examination, however, make it uncertain whether the clinically relevant diagnostic gain is also associated with cost savings. AIM: To evaluate the incremental cost-effectiveness ratio of capsule enteroscopy in patients with obscure gastrointestinal bleeding. METHODS: Retrospective study was carried out in nine Italian gastroenterology units from 2003 to 2005. Data on 369 consecutive patients with obscure gastrointestinal bleeding were collected. The diagnostic yield of capsule enteroscopy vs. other imaging procedures was evaluated as a measure of efficacy. The values of Diagnosis Related Group 175 (euro 1884.00 for obscure-occult bleeding and euro 2141.00 for obscure-overt bleeding) were calculated as measures of economic outcomes in the cost analysis. RESULTS: Obscure and occult gastrointestinal bleeding was recorded in 177 patients (48%) with a mean duration of anemia history of 17.6+/-20.7 months. Among patients, 60.9% had had at least one hospital admission, 21.2% at least two, and 1.2% of obscure bleeders up to nine admissions. Overall, 58.4% of patients had positive findings with capsule enteroscopy compared with 28.0% with other imaging procedures (P<0.001). The mean cost of a positive diagnosis with capsule enteroscopy was euro 2090.76 and that of other procedures was euro 3828.83 with a mean cost saving of euro 1738.07 (P<0.001) for one positive diagnosis. CONCLUSIONS: Capsule enteroscopy is a cost-saving approach in the evaluation of patients with obscure gastrointestinal bleeding.

Video capsule enteroscopy in the diagnosis of celiac disease: a multicenter study.

OBJECTIVES: Duodenal biopsy is the current gold standard for diagnosis of celiac disease. Videocapsule endoscopy examines the entire small bowel and allows visualization of mucosal villi. We evaluated the potential of videocapsule endoscopy in assessing the severity and extent of mucosal changes in patients with suspected celiac disease. METHODS: Consecutive patients with signs/symptoms suggesting celiac disease and positive anti-gliadin and/or anti-endomysial and/or anti-tissue transglutaminase antibodies underwent upper gastrointestinal endoscopy and videocapsule endoscopy. Duodenal biopsies were classified according to modified Marsh's criteria. Capsule findings were evaluated for the presence of lesions compatible with celiac disease (scalloping of duodenal folds, fissures, flat mucosa, and mosaic appearance). RESULTS: Forty-three patients were studied. Duodenal histology was normal in 11 and compatible with celiac disease in 32. Using duodenal histology as the gold standard, the performance characteristics of capsule endoscopy for the diagnosis of celiac disease were: sensitivity 87.5% (95% CI 76.1-98.9%), specificity 90.9% (95% CI 81.0-100%), positive predictive value 96.5% (95% CI 90.1-100%), negative predictive value 71.4% (95% CI 55.8-87%), positive and negative likelihood ratios 9.6 and 0.14, respectively. Eighteen patients had mucosal changes extending beyond the duodenum, involving the entire small bowel in three. These patients tended to have more severe symptoms, but the difference was not statistically significant. Interobserver agreement for the diagnosis of celiac disease by capsule endoscopy ranged between 79.2 and 94.4%; kappa values ranged between 0.56 and 0.87. CONCLUSIONS: Videocapsule endoscopy shows good sensitivity and excellent specificity for the detection of villous atrophy in patients with suspected celiac disease.