Migration rate using fully covered metal stent in anastomotic strictures after liver transplantation: Results from the BASALT study group.

BACKGROUND AND STUDY AIM: The traditional endoscopic therapy of anastomotic strictures (AS) after orthotopic liver transplantation (OLT) is multiple ERCPs with the insertion of an increasing number of plastic stents side-by-side. Fully covered self-expanding metal stents (cSEMS) could be a valuable option to decrease the number of procedures needed or non-responders to plastic stents. This study aims to retrospectively analyse the results of AS endoscopic treatment by cSEMS and to identify any factors associated with its success. PATIENTS AND METHODS: Ninety-one patients (mean age 55.9 ± 7.6 SD; 73 males) from nine Italian transplantation centres, had a cSEMS positioned for post-OLT-AS between 2007 and 2017. Forty-nine (54%) patients were treated with cSEMS as a second-line treatment. RESULTS: All the procedures were successfully performed without immediate complications. After ERCP, adverse events occurred in 11% of cases (2 moderate pancreatitis and 8 cholangitis). In 49 patients (54%), cSEMSs migrated. After cSEMS removal, 46 patients (51%) needed further endoscopic (45 patients) or radiological (1 patient) treatments to solve the AS. Lastly, seven patients underwent surgery. Multivariable stepwise logistic regression showed that cSEMS migration was the only factor associated with further treatments (OR 2.6, 95% CI 1.0-6.6; p value 0.03); cSEMS implantation before 12 months from OLT was associated with stent migration (OR 5.2, 95% CI 1.7-16.0; p value 0.004). CONCLUSIONS: cSEMS appears to be a safe tool to treat AS. cSEMS migration is the main limitation to its routinary implantation and needs to be prevented, probably with the use of new generation anti-migration stents.

Comparison of Two Different Techniques to Assess Adalimumab Trough Levels in Patients with Crohn's Disease.

BACKGROUND AND AIMS: Loss of response to anti-tumor necrosis factor (TNF) drugs in patients with inflammatory bowel disease is likely due to low drug serum levels, and dosing anti-TNF drug concentrations may improve patients' outcome. However, there are limited data on the diagnostic accuracy and utility of currently available assays for measuring anti-TNF levels. In this study, our aim was to compare serum adalimumab concentrations with two different techniques. METHODS: We assessed serum adalimumab concentrations in 23 patients with Crohn's disease during a 96-week follow-up period. Adalimumab trough levels were assessed using a sandwich principle-based enzyme-linked immunosorbent assay (ELISA) and a homogeneous mobility shift assay (HMSA). RESULTS: At week 48, adalimumab trough levels were significantly lower in patients who experienced relapse compared to patients in remission, using both ELISA and HMSA methods: 4.8 mcg/mL (2.4-7.2 mcg/mL) vs. 7.5 mcg/mL (6.6-8.4 mcg/mL) (P=0.01) and 6.5 mcg/mL (3-10 mcg/mL) vs. 11.6 mcg/mL (7-16.2 mcg/ml) (P=0.004), respectively. Similar results were obtained at week 96: 5.9 mcg/mL (3.3-8.5 mcg/mL) vs. 12.8 mcg/mL (9.4-16.2 mcg/mL) (P=0.001) and 4.1 mcg/mL (1.6-6.6 mcg/mL) vs. 7.5 mcg/mL (5.7-9.3 mcg/mL) (P=0.009), respectively. There was a significant correlation between ELISA and HMSA adalimumab trough levels at both 48 (r = 0.691, P=0.0003) and 96 week (r = 0.822, P=0.0001). CONCLUSIONS: ELISA and HMSA assays are accurate methods to assess adalimumab trough levels in patients with Crohn's disease and those who experience loss of response. The preferential use of one of the two techniques should be based on local availability and physicians' experience.

Adalimumab is more effective than azathioprine and mesalamine at preventing postoperative recurrence of Crohn's disease: a randomized controlled trial.

OBJECTIVES: Postsurgical recurrence of Crohn's disease (CD) is very frequent and, to date, only infliximab has been shown to be useful in preventing it. The efficacy of adalimumab (ADA) is poorly known. We evaluated whether the administration of ADA after resective intestinal surgery reduces postoperative CD recurrence. METHODS: We randomly assigned 51 patients with CD who had undergone ileocolonic resection to receive after 2 weeks from surgery ADA at the dose of 160/80/40 mg every two weeks, azathioprine (AZA) at 2 mg/kg/day, or mesalamine at 3 g/day, and they were followed up for 2 years. The primary end point was the proportion of patients with endoscopic and clinical recurrence. Secondary end point was the assessment of quality of life by means of a previously validated questionnaire. RESULTS: The rate of endoscopic recurrence was significantly lower in ADA (6.3%) compared with the AZA (64.7%; odds ratio (OR)=0.036 (95% confidence interval (CI) 0.004-0.347)) and mesalamine groups (83.3%; OR=0.013 (95% CI 0.001-0.143)). There was a significantly lower proportion of patients in clinical recurrence in the ADA group (12.5%) compared with the AZA (64.7%; OR=0.078 (95% CI 0.013-0.464)) and mesalamine groups (50%; (OR=0.143 (95% CI 0.025-0.819)). The quality of life was higher in the ADA (202) than in the AZA (90; OR=0.028 (95% CI 0.004-0.196)) and mesalamine groups (98; OR=0.015 (95% CI 0.002-0.134)). CONCLUSIONS: The administration of ADA after intestinal resective surgery was greatly effective in preventing endoscopic and clinical recurrence of CD. Further larger studies are necessary to confirm the therapeutic advantage and to show the economic implications of biologic therapy in this field.

Prevention of postoperative recurrence of Crohn's disease by Adalimumab: a case series.

Adalimumab, an anti-TNF-α monoclonal antibody, was found to be effective for the treatment of luminal Crohn's disease (CD), but its efficacy for the prevention of postoperative recurrence of CD is still unknown. Here, we present a case series of six patients who underwent resection for an ileocecal stricture caused by CD. Surgery removed the involved ileocolon, and pathology confirmed the presence of a fibrotic stricture. Two weeks after the operation, they were given Adalimumab at the dose of 160/80/40 mg every 2 weeks and were followed up. Since then, they have been disease-free for ≈ 3 years after surgery on clinical, radiological, and endoscopic/histological grounds (Crohn's Disease Activity Index ≤ 110 in all occasions). Up to now, they have had no anemia, no increase in inflammatory indices, and no abnormal blood tests. These are the first cases, to our knowledge, in which Adalimumab has been successfully used to prevent the postsurgical recurrence of CD, an event so far considered to be mandatory. Further large placebo-controlled studies are necessary to show the therapeutic advantage and the economic implications of these observations.

Overweight is a risk factor for both erosive and non-erosive reflux disease.

INTRODUCTION: Studies have reported that the association between overweight and erosive oesophagitis is very strong, whilst seeming less consistent with non-erosive reflux disease. AIM: We have hypothesized that this difference may be due to the heterogeneity of endoscopy-negative population. METHODS: We studied 81 patients with erosive oesophagitis, 48 controls and 295 endoscopy-negative patients classified by impedance-pH-testing as: (1) pH-POS (abnormal acid exposure); (2) hypersensitive oesophagus (normal acid exposure/SAP+); (3) functional heartburn (normal acid exposure/SAP-). Body mass index was also calculated. RESULTS: Mean body mass index was significantly higher (p<0.05) in erosive oesophagitis than in endoscopy-negative patients as a whole and controls [27 (18-40) vs. 25 (16-48) vs. 23 (16-34)]. However, the separation of endoscopy-negative patients showed that mean body mass index was higher (p<0.05) in those with increased acid exposure time [26 (18-45)] than in hypersensitive oesophagus [24 (16-48)]. The former subgroup was similar to erosive oesophagitis, whilst the latter one to both functional heartburn [23 (16-34)] and controls (p=ns). Increased body mass index represented a risk factor for erosive oesophagitis (odds ratio 1.4; 95% confidence interval, 1.2-1.6) and non-erosive reflux disease pH-POS subgroup (odds ratio 1.35; 95% confidence interval, 1.2-1.5). CONCLUSION: Our study shows that overweight represents an important risk factor for erosive oesophagitis and pH-POS non-erosive reflux disease and not for hypersensitive oesophagus and functional heartburn. This provides an explanation for the previously reported lesser role of this variable in non-erosive reflux disease population.

The added value of impedance-pH monitoring to Rome III criteria in distinguishing functional heartburn from non-erosive reflux disease.

INTRODUCTION: Functional heartburn is defined by Rome III criteria as an endoscopy-negative condition with normal oesophageal acid exposure time, negative symptom association to acid reflux and unsatisfactory response to proton pump inhibitors. These criteria underestimated the role of non-acid reflux. AIM: To assess the contribution of impedance-pH with symptom association probability (SAP) analysis in identifying endoscopy-negative patients with reflux disease and separating them from functional heartburn. METHODS: Consecutive endoscopy-negative patients treated with proton pump inhibitors (n=219) undergoing impedance-pH monitoring off-therapy were analysed. Distal acid exposure time, reflux episodes, SAP and symptomatic response to proton pump inhibitors were measured. RESULTS: Based on impedance-pH/SAP, 67 (31%) patients were pH+/SAP+, 6 (2%) pH+/SAP-, 83 (38%) hypersensitive oesophagus and 63 (29%) functional heartburn. According to pH-metry alone/response to proton pump inhibitors, 62 (28%) were pH+/SAP+, 11 (5%) pH+/SAP-, 61 (28%) hypersensitive oesophagus and 85 (39%) functional heartburn. In the normal-acid exposure population the contribution of impedance-pH/SAP compared to pH-metry alone/response to proton pump inhibitors in identifying patients with reflux disease and functional heartburn resulted to be 10%. In patients with abnormal-acid exposure, the contribution of impedance-pH/SAP increased by 3%. CONCLUSION: Comparing impedance-pH testing with pH-metry alone plus the response to proton pump inhibitor therapy demonstrated that the latter ones cause underestimation of reflux disease patients and overestimation of functional heartburn patients.