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Abstracts to Falk Gastro-Info 5/2020

Am J Gastroenterol. 2020;115(2):281–93

Chey WD, Lembo AJ, Rosenbaum DP

Efficacy of tenapanor in treating patients with irritable bowel syndrome with constipation: A 12-week, placebo-controlled phase 3 trial (T3MPO-1)

Objectives: Tenapanor is a first-in-class, minimally absorbed, small-molecule inhibitor of the gastrointestinal sodium/hydrogen exchanger isoform 3. This phase 3 trial assessed the efficacy and safety of tenapanor 50 mg b.i.d. for the treatment of patients with constipation-predominant irritable bowel syndrome (IBS-C).
Methods: In this phase 3, double-blind study, patients with IBS-C were randomized to tenapanor 50 mg b.i.d. or placebo b.i.d. for 12 weeks followed by a 4-week randomized withdrawal period. The primary efficacy variable was the proportion of patients who reported a reduction in average weekly worst abdominal pain of ≥ 30.0% and an increase of ≥ 1 complete spontaneous bowel movement from baseline, both in the same week, for ≥ 6 weeks of the 12-week treatment period.
Results: Of the 629 randomized patients with IBS-C, 606 (96.3%) were included in the intention-to-treat analysis set (tenapanor: n = 307; placebo: n = 299) and 533 (84.7%) completed the 12-week treatment period. In the intention-to-treat analysis set (mean age 45 years, 81.4% women), a significantly greater proportion of patients treated with tenapanor met the primary end point than patients treated with placebo (27.0% vs. 18.7%, p = 0.020). Abdominal symptoms and global symptoms of IBS also improved with tenapanor (p < 0.05 vs. placebo). Diarrhea was the most commonly reported adverse event, resulting in study drug discontinuation in 6.5% and 0.7% of patients receiving tenapanor and placebo, respectively, during the 12-week treatment period.

Discussion: Tenapanor 50 mg b.i.d. improved constipation-predominant irritable bowel syndrome (IBS-C) symptoms and was generally well tolerated, offering a potential new treatment option for patients with IBS-C.

W.D. Chey, M.D., Professor of Internal Medicine, Division of Gastroenterology and Hepatology, Department of Medicine, University of Michigan Health System, 1500 E. Medical Center Drive, Ann Arbor, MI 48109, USA, E-Mail: wchey@umich.edu

Lancet Gastroenterol Hepatol. 2020;5(3):276–84

Waljee AK, Higgins PDR, Jensen CB, Villumsen M, Cohen-Mekelburg SA, Wallace BI, Berinstein JA, Allin KH, Jess T

Anti-tumor necrosis factor-α therapy and recurrent or new primary cancers in patients with inflammatory bowel disease, rheumatoid arthritis, or psoriasis and previous cancer in Denmark: A nationwide, population-based cohort study

Background: Safety of anti-tumor necrosis factor-α (TNFα) therapy in people with a history of cancer and with an immune-mediated disease is unknown. The authors aimed to assess the risk of recurrence of initial cancer or development of a new primary cancer after treatment with anti-TNFα therapy.
Methods: In this Danish, population-based cohort study they recruited adults (≥ 18 years) with inflammatory bowel disease (IBD), rheumatoid arthritis, or psoriasis and a primary cancer diagnosed between January 1, 1999 and December 31, 2016. Patients were recruited from the prospectively recorded Danish National Patient Registry and the Danish Cancer Registry. Participants were matched 1:10 between the treatment group who received anti-TNFα therapy and the control group (no anti-TNFα therapy) and individuals with a cancer diagnosed before their first anti-TNFα treatment (or before matching date for controls), individuals diagnosed with IBD, rheumatoid arthritis, or psoriasis after anti-TNFα initiation (or respective match date for controls), and individuals who received anti-TNFα with fewer than 5 matched controls were excluded. Using adjusted Cox-proportional hazards regression, the authors estimated the primary outcome of development of recurrent or new primary cancer in patients who received anti-TNFα therapy compared with patients who did not receive this therapy, matched by sex, immune-mediated disease type, cancer type, and time from initial cancer diagnosis to first anti-TNFα registration.
Findings: Overall, 25,738 patients with immune-mediated disease and a history of cancer were identified. 434 patients who received anti-TNFα therapy after their initial cancer were matched to 4328 patients in the control group. During 18,752 person-years (median 5.6 years [IQR, 2.8–7.9]) of follow-up, 635 individuals developed recurrent or new primary cancer, 72 of whom had received anti-TNFα therapy and 563 of whom were in the control group. The median time between anti-TNFα treatment and recurrent or new primary cancer diagnosis was 2.8 years (IQR, 1.7–5.4). The incidence of recurrent or new primary cancer development was 30.3 cases (95% confidence interval [CI]: 24.0–38.2) per 1000 person-years in the anti-TNFα treatment group and 34.4 cases (95% CI: 31.7–37.3) per 1000 person-years in the control group, yielding an adjusted hazard ratio of 0.82 (95% CI: 0.61–1.11).

Interpretation: Use of anti-tumor necrosis factor-α (TNFα) therapy was not associated with recurrent or new primary cancer development in patients with previous cancer. Timing of anti-TNFα therapy after an initial cancer diagnosis did not influence recurrent or new primary cancer development. This observation might guide clinical decision making among providers treating immune-mediated diseases with anti-TNFα medications.

A.K. Waljee, M.D., VA Center for Clinical Management Research, VA Ann Arbor Healthcare System, 2215 Fuller Road, Ann Arbor, MI 48105, USA, E-Mail: awaljee@med.umich.edu

Gastroenterology. 2020;158(3):515–26.e10

D'Haens G, Kelly O, Battat R, Silverberg MS, Laharie D, Louis E, Savarino E, Bodini G, Yarur A, Boland BS, Afif W, Li XJ, Hale M, Ho J, Kondragunta V, Huang B, Kuy C, Okada L, Hester KD, Bray KR, Mimms L, Jain A, Singh S, Collins A, Valasek MA, Sandborn WJ, Vermeire S, Dulai PS

Development and validation of a test to monitor endoscopic activity in patients with Crohn's disease based on serum levels of proteins

Background and aims: Non-invasive tests to measure endoscopic activity in patients with Crohn's disease (CD) have limitations. The authors aimed to develop a test to identify patients in remission, based on endoscopic analysis, and monitor CD activity based on serum levels of proteins.
Methods: They developed a test to measure 13 proteins in blood (ANG1, ANG2, CRP, SAA1, IL7, EMMPRIN, MMP1, MMP2, MMP3, MMP9, TGFA, CEACAM1, and VCAM1), called the endoscopic healing index (EHI), using samples from 278 patients with CD from a multinational training cohort and validated the test using 2 independent cohorts of patients with CD: 116 biologic-naive patients with early-stage CD (validation cohort 1) and 195 biologic-exposed patients with chronic CD (validation cohort 2). The ability of the test to identify patients with active disease versus patients in remission (defined as a simple endoscopic score for CD of ≤ 2 and ≤ 1 in each segment, or a total CD endoscopic index of severity score < 3) was assessed by using area under receiver-operating characteristic curve (AUROC) analysis. The diagnostic accuracy of the test was compared with that of measurement of serum C-reactive protein (CRP) and fecal calprotectin (FC).
Results: The EHI scores range from 0 to 100 units; higher scores indicate more severe CD activity, based on endoscopy findings. The EHI identified patients in remission with an AUROC of 0.962 in validation cohort 1 (95% confidence interval [CI]: 0.942–0.982) and an AUROC of 0.693 in validation cohort 2 (95% CI: 0.619–0.767), regardless of CD location or phenotype. A cut-off value of 20 points identified patients in remission with the highest level of sensitivity (97.1% in validation cohort 1 and 83.2% in validation cohort 2), with specificity values of 69.0% and 36.6%, respectively. A cut-off value of 50 points identified patients in remission with the highest level of specificity (100% in validation cohort 1 and 87.8% in validation cohort 2), with sensitivity values of 37.3% and 30.0%, respectively. The EHI identified patients in remission with a significantly higher AUROC value than the test for CRP (0.876, p < 0.001 in validation cohort 1 and 0.624, p = 0.109 in validation cohort 2). In analysis of patients with available FC measurements, the AUROC value for the EHI did not differ significantly from that of measurement of FC (AUROC, 0.950 for EHI vs. AUROC, 0.923 for FC; p = 0.147 in validation cohort 1 and AUROC, 0.803 for EHI vs. AUROC, 0.854 for FC; p = 0.298 in validation cohort 2).

Conclusions: The authors developed an index called the endoscopic healing index (EHI) to identify patients with Crohn’s disease (CD) in endoscopic remission based on blood levels of 13 proteins. The EHI identified patients with resolution of endoscopic disease activity, with good overall accuracy, although with variation between the 2 cohorts assessed. The EHI AUROC (area under receiver operating characteristic curve) values were comparable to measurement of fecal calprotectin and higher than measurement of serum C-reactive protein. The test might be used in practice to assess endoscopic activity in patients with CD.

Prof. Dr. G. D’Haens, Department of Gastroenterology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1100 DZ Amsterdam, The Netherlands, E-Mail: g.dhaens@amc.uva.nl

J Hepatol. 2020;72(4):643–57

Hajarizadeh B, Cunningham EB, Valerio H, Martinello M, Law M, Janjua NZ, Midgard H, Dalgard O, Dillon J, Hickman M, Bruneau J, Dore GJ, Grebely J

Hepatitis C reinfection after successful antiviral treatment among people who inject drugs: A meta-analysis

Background and aims: Hepatitis C virus (HCV) reinfection following successful treatment can compromise treatment outcomes. This systematic review assessed the rate of HCV reinfection following treatment among people with recent drug use and those receiving opioid agonist therapy (OAT).
Methods: The authors searched bibliographic databases and conference abstracts for studies assessing post-treatment HCV reinfection rates among people with recent drug use (injecting or non-injecting) or those receiving OAT. Meta-analysis was used to cumulate reinfection rates and meta-regression was used to explore heterogeneity across studies.
Results: 36 studies were included (6311 person-years of follow-up). The overall rate of HCV reinfection was 5.9/100 person-years (95% confidence interval [CI]: 4.1–8.5) among people with recent drug use (injecting or non-injecting), 6.2/100 person-years (95% CI: 4.3–9.0) among people recently injecting drugs, and 3.8/100 person-years (95% CI: 2.5–5.8) among those receiving OAT. Reinfection rates were comparable following interferon-based (5.4/100 person-years, 95% CI: 3.1–9.5) and direct-acting antiviral (3.9/100 person-years, 95% CI: 2.5–5.9) therapy. In stratified analysis, reinfection rates were 1.4/100 person-years (95% CI: 0.8–2.6) among people receiving OAT with no recent drug use, 5.9/100 person-years (95% CI: 4.0–8.6) among people receiving OAT with recent drug use, and 6.6/100 person-years (95% CI: 3.4–12.7) among people with recent drug use not receiving OAT. In meta-regression analysis, longer follow-up was associated with lower reinfection rate (adjusted rate ratio [aRR] per year increase in mean/median follow-up = 0.77, 95% CI: 0.69–0.86). Compared with people receiving OAT with no recent drug use, those with recent drug use receiving OAT (aRR = 3.50, 95% CI: 1.62–7.53), and those with recent drug use not receiving OAT (aRR = 3.96, 95% CI: 1.82–8.59) had higher reinfection rates.

Conclusion: Hepatitis C virus reinfection risk following treatment was higher among people with recent drug use and lower among those receiving opioid agonist therapy. The lower rates of reinfection observed in studies with longer follow-up suggested higher reinfection risk early post-treatment.

Dr. B. Hajarizadeh, The Kirby Institute, UNSW Sydney, Level 6, Wallace Wurth Building, High Street, Kensington, NSW 2052, Australia, E-Mail: bhajarizadeh@kirby.unsw.edu.au

Hepatology. 2020;71(3):808–19

Kanwal F, Kramer JR, Li L, Dai J, Natarajan Y, Yu X, Asch SM, El-Serag HB

Effect of metabolic traits on the risk of cirrhosis and hepatocellular cancer in non-alcoholic fatty liver disease

Background and aims: Non-alcoholic fatty liver disease (NAFLD) is now the most common liver condition. Predicting its progression could help clinicians manage and potentially prevent complications. The authors evaluated the independent and joint effects of metabolic traits on the risk of cirrhosis and hepatocellular carcinoma (HCC) among patients with NAFLD.
Approach and results: They assembled a retrospective cohort of patients with NAFLD diagnosed at 130 facilities in the Veterans Administration between January 1, 2004, and December 31, 2008, with follow-up through December 31, 2015. Competing risk-adjusted cause-specific Cox models were performed to evaluate the effects of metabolic traits (diabetes, hypertension, dyslipidemia, obesity) as additive or combined indicators on time to develop cirrhosis or HCC or a composite end point of both. Of the 271,906 patients, 22,794 developed cirrhosis, and 253 developed HCC during a mean of 9 years follow-up. At baseline, the mean body mass index was 31.6 (SD, 5.6), 28.7% had diabetes, 70.3% had hypertension, and 62.3% had dyslipidemia with substantial overlap among these traits. The risk of progression was the lowest in patients with only one or no metabolic trait. There was a stepwise increase in risk with each additional metabolic trait. Compared with patients with no metabolic trait, patients with both hypertension and dyslipidemia had 1.8-fold higher risk of progression to cirrhosis/HCC (hazard ratio [HR] = 1.8, 95% confidence interval [CI]: 1.59–2.06); the risk was 2.6-fold higher in patients with diabetes, obesity, dyslipidemia, and hypertension (HR = 2.6, 95% CI: 2.3–2.9). These associations were stronger for HCC. Diabetes had the strongest association with HCC in this cohort.

Conclusions: Each additional metabolic trait increased the risk of cirrhosis and hepatocellular carcinoma (HCC) in patients with non-alcoholic fatty liver disease. Diabetes conferred the highest risk of progression to HCC. Patients with diabetes and coexisting hypertension and obesity may be important targets for secondary prevention.

F. Kanwal, M.D., Professor of Medicine, Michael E. DeBakey VA Medical Center, 2002 Holcombe Blvd. (152), Houston, TX 77030, USA, E-Mail: kanwal@bcm.edu

Hepatology. 2020;71(3):1009–22

Maiwall R, Pasupuleti SSR, Bihari C, Rastogi A, Kumar Singh P, Naik V, Singh A, Jain P, Kumar A, Mukund A, Mathur RP, Kumar G, Kumar Sarin S

Incidence, risk factors, and outcomes of transition of acute kidney injury to chronic kidney disease in cirrhosis: A prospective cohort study

Transition to chronic kidney disease (CKD) after an episode of acute kidney injury (AKI) is known in patients without cirrhosis. The authors studied the incidence and risk factors for development of CKD in patients with cirrhosis. Competing risk analysis was performed to identify risk factors for CKD development. Of 818 patients with cirrhosis (age, 50.4 ± 11.8 years; 84% males; Model for End-Stage Liver Disease [MELD], 19.9 ± 9.9), 36% had AKI at enrollment, 27% had previous AKI, and 61% developed new episodes of AKI during the follow-up period. CKD developed in 269 (33%) patients. Serum cystatin C (CysC; subdistribution hazard ratio [SHR] = 1.58, 95% confidence interval [CI]: 1.07–2.33), episodes of previous AKI (SHR = 1.26, 95% CI: 1.02–1.56), and AKI stage at enrollment (no AKI [SHR = 1] vs. stage 1 [SHR = 3.28, 95% CI: 1.30–8.25] vs. stage 2 [SHR = 4.33, 95% CI: 1.76–10.66] vs. stage 3 [SHR = 4.5, 95% CI: 1.59–12.73]) were identified as baseline risk factors for CKD development. On time-varying competing risk analysis, MELD (SHR = 1.01, 95% CI: 1.00–1.03), number of AKI episodes (SHR = 1.25, 95% CI: 1.15–1.37), and CysC (SHR = 1.38, 95% CI: 1.01–1.89) predicted CKD development. Development of CKD was associated with higher risk of death. Reduction in glomerular filtration rate not meeting CKD criteria was observed in 66% of patients with cirrhosis, more so in those with previous AKI episodes and a high CysC level and MELD score. Renal histology, available in 55 patients, showed tubulointerstitial injury in 86%, cholemic nephrosis in 29%, and glomerular changes in 38%.

Conclusion: Almost two-thirds of patients with cirrhosis develop episodes of acute kidney injury (AKI) and reduction in glomerular filtration rate; one-third progress to chronic kidney disease (CKD), resulting in adverse outcomes. Higher MELD and CysC levels and number of AKI episodes predict development of CKD in patients with cirrhosis.

Prof. Dr. S. Kumar Sarin, Department of Hepatology, Institute of Liver and Biliary Sciences (ILBS), D-1 Vasant Kunj, New Delhi 110070, Indien, E-Mail: sksarin@ilbs.in

Gastroenterology. 2020;158(1):111–22.e10

Hirano I, Dellon ES, Hamilton JD, Collins MH, Peterson K, Chehade M, Schoepfer AM, Safroneeva E, Rothenberg ME, Falk GW, Assouline-Dayan Y, Zhao Q, Chen Z, Swanson BN, Pirozzi G, Mannent L, Graham NMH, Akinlade B, Stahl N, Yancopoulos GD, Radin A

Efficacy of dupilumab in a phase 2 randomized trial of adults with active eosinophilic esophagitis

Background and aims: Eosinophilic esophagitis (EoE) is an allergen-mediated inflammatory disease with no approved treatment in the United States. Dupilumab, a VelocImmune-derived human monoclonal antibody against the interleukin (IL)-4 receptor, inhibits IL-4 and IL-13 signaling. Dupilumab is effective in the treatment of allergic, atopic, and type 2 diseases, so the authors assessed its efficacy and safety in patients with EoE.
Methods: They performed a phase 2 study of adults with active EoE (2 episodes of dysphagia/week with peak esophageal eosinophil density ≥ 15 eosinophils [eos] per high-power field [HPF]), from May 12, 2015, through November 9, 2016, at 14 sites. Participants were randomly assigned to groups that received weekly subcutaneous injections of dupilumab (300 mg, n = 23) or placebo (n = 24) for 12 weeks. The primary end point was change from baseline to week 10 in Straumann Dysphagia Instrument (SDI) patient-reported outcome (PRO) score. Histologic features of EoE (peak esophageal intraepithelial eosinophil count and EoE histologic scores), endoscopically visualized features (endoscopic reference score), esophageal distensibility, and safety were also assessed.
Results: The mean SDI PRO score was 6.4 when the study began. In the dupilumab group, SDI PRO scores were reduced by a mean value of 3.0 at week 10 compared with a mean reduction of 1.3 in the placebo group (p = 0.0304). At week 12, dupilumab reduced the peak esophageal intraepithelial eosinophil count by a mean 86.8 eos/HPF (reduction of 107.1%; p < 0.0001 vs. placebo), the EoE-histologic scoring system severity score by 68.3% (p < 0.0001 vs. placebo), and the endoscopic reference score by 1.6 (p = 0.0006 vs. placebo). Dupilumab increased esophageal distensibility by 18% vs. placebo (p < 0.0001). Higher proportions of patients in the dupilumab group developed injection-site erythema (35% vs. 8% in the placebo group) and nasopharyngitis (17% vs. 4% in the placebo group).

Conclusions: In a phase 2 trial of patients with active eosinophilic esophagitis, dupilumab reduced dysphagia, histologic features of disease (including eosinophilic infiltration and a marker of type 2 inflammation), and abnormal endoscopic features compared with placebo. Dupilumab increased esophageal distensibility and was generally well tolerated.

I. Hirano, M.D., Professor of Medicine, Northwestern University Feinberg School of Medicine, 259 East Erie Street, 16th Floor, Chicago, IL 60611, USA, E-Mail: i-hirano@northwestern.edu

Gastroenterology. 2020;158(3):506–14.e2

Ducrotte P, Coffin B, Bonaz B, Fontaine S, Bruley Des Varannes S, Zerbib F, Caiazzo R, Grimaud JC, Mion F, Hadjadj S, Valensi PE, Vuitton L, Charpentier G, Ropert A, Altwegg R, Pouderoux P, Dorval E, Dapoigny M, Duboc H, Benhamou PY, Schmidt A, Donnadieu N, Gourcerol G, Guerci B; ENTERRA Research Group

Gastric electrical stimulation reduces refractory vomiting in a randomized crossover trial

Background and aims: There have been conflicting results from trials of gastric electrical stimulation (GES) for treatment of refractory vomiting, associated or not with gastroparesis. The authors performed a large, multicenter, randomized, double-blind trial with crossover to study the efficacy of GES in patients with refractory vomiting, with or without gastroparesis.
Methods: For 4 months, they assessed symptoms in 172 patients (66% women; mean age ± standard deviation, 45 ± 12 years; 133 with gastroparesis) with chronic (> 12 months) of refractory vomiting (idiopathic, associated with a type 1 or 2 diabetes, or postsurgical). A GES device was implanted and left unactivated until patients were randomly assigned, in a double-blind manner, to groups that received 4 months of stimulation parameters (14 Hz, 5 mA, pulses of 330 µs) or no stimulation (control); 149 patients then crossed over to the other group for 4 months. Patients were examined at the end of each 4-month period (at 5 and 9 months after implantation). Primary end points were vomiting score, ranging from 0 (daily vomiting) to 4 (no vomiting), and the quality of life, assessed by the Gastrointestinal Quality of Life Index scoring system. Secondary end points were changes in other digestive symptoms, nutritional status, gastric emptying, and control of diabetes.
Results: During both phases of the crossover study, vomiting scores were higher in the group with the device on (median score, 2) than the control group (median score, 1; p < 0.001), in diabetic and non-diabetic patients. Vomiting scores increased significantly when the device was ON in patients with delayed (p < 0.01) or normal gastric emptying (p = 0.05). Gastric emptying was not accelerated during the ON period compared with the OFF period. Having the GES turned on was not associated with increased quality of life.

Conclusions: In a randomized crossover study, it was found that gastric electrical stimulation reduced the frequency of refractory vomiting in patients with and without diabetes, although it did not accelerate gastric emptying or increase of quality of life.

Dr. Dr. G. Gourcerol, Department of Physiology, Rouen University Hospital, 1, rue de Germont, 76031 Rouen, France, E-Mail: guillaume.gourcerol@chu-rouen.fr

Gastrointest Endosc. 2020;91(1):70–7.e1

Huang RJ, Ende AR, Singla A, Higa JT, Choi AY, Lee AB, Whang SG, Gravelle K, D'Andrea S, Bang SJ, Schmidt RA, Yeh MM, Hwang JH

Prevalence, risk factors, and surveillance patterns for gastric intestinal metaplasia among patients undergoing upper endoscopy with biopsy

Background and aims: Gastric intestinal metaplasia (GIM) is an important precursor lesion to gastric cancer, the second leading cause of cancer death worldwide. There exist few data regarding the prevalence of, risk factors for, and clinical practice patterns regarding GIM in the United States. Furthermore, there are currently no U.S. guidelines regarding screening/surveillance for GIM.
Methods: All consecutive upper endoscopic procedures from 2 academic medical centers in Seattle between 1999 and 2014 were reviewed. Demographic, clinical, and endoscopic covariates were recorded at time of endoscopy. Procedures with gastric biopsy were matched to final the histologic diagnoses, including the presence of Helicobacter pylori. Cases of GIM and dysplasia were recorded and compared with non-GIM controls using univariate and multivariable regression. Surveillance patterns for cases of GIM were recorded.
Results: Data from 36,799 upper endoscopies, 17,710 gastric biopsies, 2073 cases of GIM, 43 cases of dysplasia, and 78 cases of gastric cancer were captured. The point prevalence of GIM was 11.7% in patients who underwent gastric biopsy. Non-white race (p < 0.001), increasing age (p < 0.001), and presence of H. pylori (p < 0.001) were associated with GIM. If GIM was present, increasing age (p < 0.001) and male gender (p < 0.001) were associated with progression, and the presence of H. pylori (p < 0.001) was inversely associated with progression to dysplasia/gastric cancer. Few cases of GIM/dysplasia/gastric cancer were identified during procedures for GIM screening/surveillance. Only 16% of patients with a diagnosis of GIM received a recommendation for surveillance.

Conclusions: There is a high prevalence of gastric intestinal metaplasia (GIM) among non-white and Hispanic Americans. Risk factors for development of GIM may be distinct from the risk factors for progression to gastric cancer.

J.H. Hwang, M.D., Ph.D., Professor of Medicine, Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University, 300 Pasteur Drive, H0268, MC: 5244, Stanford, CA 94305, USA, E-Mail: jooha@stanford.edu

Gastrointest Endosc. 2020;91(2):361–9.e3

Lakhtakia S, Reddy N, Dolak W, Ponchon T, Bruno MJ, Bourke MJ, Neuhaus H, Roy A, González-Huix Lladó F, Kortan PP, Peetermans J, Rousseau M, Costamagna G, Devière J; Benign Biliary Stenoses Working Group

Long-term outcomes after temporary placement of a self-expanding fully covered metal stent for benign biliary strictures secondary to chronic pancreatitis

Background and aims: Temporary single, fully covered self-expanding metal stent (FCSEMS) placement for benign biliary strictures (BBSs) associated with chronic pancreatitis (CP) may require fewer interventions than endotherapy with multiple plastic stents and may carry less morbidity than biliary diversion surgery. This study aimed to assess long-term outcomes in CP-associated BBSs after FCSEMS placement and removal.
Methods: In this open-label, multinational, prospective study, subjects with CP and a BBS treated with FCSEMS placement with scheduled removal at 10 to 12 months were followed for 5 years after FCSEMS indwell. Kaplan-Meier analyses assessed BBS resolution and cumulative probability of freedom from recurrent stent placement to 5 years after FCSEMS indwell.
Results: 118 patients were eligible for FCSEMS removal. At a median of 58 months (interquartile range, 44–64) post-FCSEMS indwell, the probability of remaining stent-free was 61.6% (95% confidence interval [CI]: 52.5–70.7%). In 94 patients whose BBSs resolved at the end of FCSEMS indwell, the probability of remaining stent-free 5 years later was 77.4% (95% CI: 68.4–86.4%). Serious stent-related adverse events occurred in 27 of 118 patients (22.9%); all resolved with medical therapy or repeated endoscopy. Multivariate analysis identified severe CP (hazard ratio [HR] = 2.4, 95% CI: 1.0–5.6; p = 0.046) and longer stricture length (HR = 1.2, 95% CI: 1.0–1.4; p = 0.022) as predictors of stricture recurrence.

Conclusion: In patients with symptomatic benign biliary strictures (BBSs) secondary to chronic pancreatitis (CP), 5 years after placement of a single fully covered self-expanding metal stent (FCSEMS) intended for 10 to 12 months indwell, more than 60% remained asymptomatic and stent-free with an acceptable safety profile. Temporary placement of a single FCSEMS may be considered as first-line treatment for patients with CP and BBSs.

Prof. Dr. J. Devière, Service de Gastro-Entérologie et d’Hépato-Pancréatologie, Hôpital Erasme, Université Libre de Bruxelles, Route de Lennik 808, 1070 Brussels, Belgium, E-Mail: jdeviere@ulb.ac.be