Kanis SL, Modderman S, Escher JC, Erler N, Beukers R, de Boer N, Bodelier A, Depla ACTM, Dijkstra G, van Dijk ARM, Gilissen L, Hoentjen F, Jansen JM, Kuyvenhoven J, Mahmmod N, Mallant-Hent RC, van der Meulen-de Jong AE, Noruzi A, Oldenburg B, Oostenbrug LE, Ter Borg PCJ, Pierik M, Romberg-Camps M, Thijs W, West R, de Lima A, van der Woude CJ; Initiative on Crohns and Colitis (ICC)
Health outcomes of 1000 children born to mothers with inflammatory bowel disease in their first 5 years of life
Objective: The aim of this study was to describe the long-term health outcomes of children born to mothers with inflammatory bowel disease (IBD) and to assess the impact of maternal IBD medication use on these outcomes.
Design: The authors performed a multicenter retrospective study in The Netherlands. Women with IBD who gave birth between 1999 and 2018 were enrolled from 20 participating hospitals. Information regarding disease characteristics, medication use, lifestyle, pregnancy outcomes and long-term health outcomes of children was retrieved from mothers and medical charts. After consent of both parents, outcomes until 5 years were also collected from general practitioners. The primary aim was to assess infection rate and the secondary aims were to assess adverse reactions to vaccinations, growth, autoimmune diseases and malignancies.
Results: 1000 children born to 626 mothers (381 [61%] Crohn's disease, 225 [36%] ulcerative colitis and 20 [3%] IBD unclassified) were included. In total, 196 (20%) had intrauterine exposure to anti-tumor necrosis factor-alpha (anti-TNFα) (60 with concomitant thiopurine) and 240 (24%) were exposed to thiopurine monotherapy. The 564 children (56%) not exposed to anti-TNFα and/or thiopurine served as control group. There was no association between adverse long-term health outcomes and in utero exposure to IBD treatment. The authors did find an increased rate of intrahepatic cholestasis of pregnancy (ICP) in case thiopurine was used during pregnancy without affecting birth and long-term health outcomes of children. All outcomes correspond with the general age-adjusted population.
Conclusion: In the present study, no association was found between in utero exposure to anti-tumor necrosis factor-alpha and/or thiopurine and the long-term outcomes antibiotic-treated infections, severe infections needing hospital admission, adverse reactions to vaccinations, growth failure, autoimmune diseases and malignancies.
Dr. S.L. Kanis, Gastroenterology and Hepatology, Erasmus Medical Center, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands,
Am J Gastroenterol. 2021;116(6):1294–303
Chey WD, Lembo AJ, Yang Y, Rosenbaum DP
Efficacy of tenapanor in treating patients with irritable bowel syndrome with constipation: A 26-week, placebo-controlled phase 3 trial (T3MPO-2)
Introduction: 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 long-term efficacy and safety of tenapanor 50 mg b.i.d. for the treatment of patients with irritable bowel syndrome with constipation (IBS-C).
Methods: In this randomized double-blind study, patients with IBS-C received tenapanor 50 mg b.i.d. or placebo b.i.d. for 26 weeks. The primary end point was the proportion of patients who had a reduction of ≥ 30.0% in average weekly worst abdominal pain and an increase of ≥ 1 weekly complete spontaneous bowel movement from baseline, both in the same week, for ≥ 6 of the first 12 treatment weeks (6/12-week combined responder).
Results: Of the 620 randomized patients with IBS-C, 593 (95.6%) were included in the intention-to-treat analysis set (tenapanor: n = 293; placebo: n = 300) and 481 patients (77.6%) completed the 26-week treatment period. In the intention-to-treat analysis set (mean age: 45.4 years; 82.1% women), a significantly greater proportion of patients treated with tenapanor were 6/12-week combined responders than those treated with placebo (36.5% vs. 23.7%; p < 0.001). Abdominal symptoms and global symptoms of IBS were significantly improved with tenapanor compared with placebo. Diarrhea, the most common adverse event, was typically transient and mild to moderate in severity. Diarrhea led to study drug discontinuation for 19 (6.5%) and 2 (0.7%) patients receiving tenapanor and placebo, respectively.
Discussion: Tenapanor 50 mg b.i.d. improved symptoms of irritable bowel syndrome with constipation (IBS-C) over 26 weeks and was generally well tolerated, offering a potential new long-term treatment option for patients with IBS-C.
W.D. Chey, M.D., Professor of Medicine, Division of Gastroenterology, Department of Medicine, University of Michigan Health System, 1500 E Medical Center Drive, Ann Arbor, MI 48109, USA,
van Hattem WA, Shahidi N, Vosko S, Hartley I, Britto K, Sidhu M, Bar-Yishay I, Schoeman S, Tate DJ, Byth K, Hewett DG, Pellisé M, Hourigan LF, Moss A, Tutticci N, Bourke MJ
Piecemeal cold snare polypectomy versus conventional endoscopic mucosal resection for large sessile serrated lesions: A retrospective comparison across two successive periods
Objective: Large (≥ 20 mm) sessile serrated lesions (L-SSL) are premalignant lesions that require endoscopic removal. Endoscopic mucosal resection (EMR) is the existing standard of care but carries some risk of adverse events including clinically significant post-EMR bleeding and deep mural injury (DMI). The respective risk-effectiveness ratio of piecemeal cold snare polypectomy (p-CSP) in L-SSL management is not fully known.
Design: Consecutive patients referred for L-SSL management were treated by p-CSP from April 2016 to January 2020 or by conventional EMR in the preceding period between July 2008 and March 2016 at 4 Australian tertiary centers. Surveillance colonoscopies (SC) were conducted at 6 months (SC1) and 18 months (SC2). Outcomes on technical success, adverse events and recurrence were documented prospectively and then compared retrospectively between the subsequent time periods.
Results: A total of 562 L-SSL in 474 patients were evaluated of which 156 L-SSL in 121 patients were treated by p-CSP and 406 L-SSL in 353 patients by EMR. Technical success was equal in both periods (100.0% [n = 156] vs 99.0% [n = 402]). No adverse events occurred in p-CSP, whereas delayed bleeding and DMI were encountered in 5.1% (n = 18) and 3.4% (n = 12) of L-SSL treated by EMR, respectively. Recurrence rates following p-CSP were similar to EMR at 4.3% (n = 4) versus 4.6% (n = 14) and 2.0% (n = 1) versus 1.2% (n = 3) for SC1 and SC2, respectively.
Conclusions: In a historical comparison on the endoscopic management of large sessile serrated lesions (L-SSL), piecemeal cold snare polypectomy (p-CSP) is technically equally efficacious to endoscopic mucosal resection but virtually eliminates the risk of delayed bleeding and perforation. p-CSP should therefore be considered as the new standard of care for L-SSL treatment
Prof. Dr. M.J. Bourke, Gastroenterology and Hepatology, Westmead Hospital, Westmead, Hawkesbury Road & Darcy Road, NSW 2145, Australia,
J Hepatol. 2021;75(3):565–71
Tanaka A, Hirohara J, Nakano T, Matsumoto K, Chazouillères O, Takikawa H, Hansen BE, Carrat F, Corpechot C
Association of bezafibrate with transplant-free survival in patients with primary biliary cholangitis
Background and aims: A beneficial effect of bezafibrate (BZF) on symptoms and biochemical features of primary biliary cholangitis (PBC) has been reported in patients with an incomplete response to ursodeoxycholic acid (UDCA), but long-term effects on survival remain unknown. In Japan, BZF has been used as a de facto second-line therapy for PBC since 2000. Herein, the authors compared the survival rates between patients treated with and those without BZF in a large nationwide Japanese PBC cohort.
Methods: All consecutively registered patients of this cohort who started UDCA therapy from 2000 onwards and had a follow-up ≥ 1 year were included. Association between BZF exposure and mortality or need for liver transplantation (LT) was assessed using time-dependent, multivariable, and propensity score-adjusted Cox proportional hazards models. Clinical benefit was quantified using the number needed to treat (NNT).
Results: Of 3908 eligible patients, 3162 (81%) received UDCA only and 746 (19%) UDCA and BZF over 17,360 and 3932 patient-years, respectively. During follow-up, 183 deaths (89 liver-related) and 21 LT were registered. Exposure to combination therapy was associated with a significant decrease in all-cause and liver-related mortality or need for LT (adjusted hazard ratio [aHR] = 0.3253, 95% confidence interval [CI]: 0.1936–0.5466, and HR = 0.2748, 95% CI: 0.1336–0.5655, respectively; p < 0.001 for both). This association was consistent across various risk groups at baseline. The NNTs with combination therapy to prevent 1 additional death or LT over 5, 10, and 15 years were 29 (95% CI: 22–46), 14 (95% CI: 10–22), and 8 (95% CI: 6–15), respectively.
Conclusions: In a large retrospective cohort study of treatment effects in patients with primary biliary cholangitis, the addition of bezafibrate to ursodeoxycholic acid was associated with improved prognosis.
Prof. Dr. A. Tanaka, Department of Medicine, Teikyo University School of Medicine; 2-11-1, Kaga, Itabashi-ku, Tokyo 173-8605, Japan,
Dr. C. Corpechot, Unité Hépato-Gastro-Entérologie, Hôpital Saint-Antoine, Assistance Publique - Hôpitaux de Paris (AP-HP), 184, rue du Faubourg Saint-Antoine, 75571 Paris, Cedex 12, France,
J Hepatol. 2021;75(2):342–50
Martínez J, Hernández-Gea V, Rodríguez-de-Santiago E, Téllez L, Procopet B, Giráldez Á, Amitrano L, Villanueva C, Thabut D, Ibañez-Samaniego L, Silva-Junior G, Genescà J, Bureau C, Trebicka J, Bañares R, Krag A, Llop E, Laleman W, Palazon JM, Castellote J, Rodrigues S, Gluud LL, Noronha-Ferreira C, Cañete N, Rodríguez M, Ferlitsch A, Schwarzer R, Mundi JL, Gronbaek H, Hernández-Guerra M, Sassatelli R, Dell'Era A, Senzolo M, Abraldes JG, Romero-Gomez M, Zipprich A, Casas M, Masnou H, Primignani M, Nevens F, Calleja JL, Jansen C, Robic MA, Conejo I, Catalina MV, Rudler M, Alvarado E, Perez-Campuzano V, Guardascione MA, Fischer P, Bosch J, García-Pagán JC, Albillos A; International Variceal Bleeding Observational Study Group and Baveno Cooperation
Bacterial infections in patients with acute variceal bleeding in the era of antibiotic prophylaxis
Background and aims: Antibiotic prophylaxis reduces the risk of infection and mortality in patients with cirrhosis and acute variceal bleeding (AVB). This study examines the incidence of, and risk factors for, bacterial infections during hospitalization in patients with AVB on antibiotic prophylaxis.
Methods: A post hoc analysis was performed using the database of an international, multicenter, observational study designed to examine the role of pre-emptive transjugular intrahepatic portosystemic shunts in patients with cirrhosis and AVB. Data were collected on patients with cirrhosis hospitalized for AVB (n = 2138) from a prospective cohort (October 2013–May 2015) at 34 referral centers, and a retrospective cohort (October 2011–September 2013) at 19 of these centers. The primary outcome was incidence of bacterial infection during hospitalization.
Results: A total of 1656 patients out of 1770 (93.6%) received antibiotic prophylaxis; third-generation cephalosporins (76.2%) and quinolones (19.0%) were used most frequently. Of the patients on antibiotic prophylaxis, 320 patients developed bacterial infection during hospitalization. Respiratory infection accounted for 43.6% of infections and for 49.7% of infected patients, and occurred early after admission (median 3 days, interquartile range [IQR], 1–6). On multivariate analysis, respiratory infection was independently associated with Child-Pugh C (odds ratio [OR] = 3.1; 95% confidence interval [CI]: 1.4–6.7), grade III–IV encephalopathy (OR = 2.8; 95% CI: 1.8–4.4), orotracheal intubation for endoscopy (OR = 2.6; 95% CI: 1.8–3.8), nasogastric tube placement (OR = 1.7; 95% CI: 1.2–2.4) or esophageal balloon tamponade (OR = 2.4; 95% CI: 1.2–4.9).
Conclusion: Bacterial infections develop in almost one-fifth of patients with acute variceal bleeding despite antibiotic prophylaxis. Respiratory infection is the most frequent, is an early event after admission, and is associated with advanced liver failure, severe hepatic encephalopathy and use of nasogastric tube, orotracheal intubation for endoscopy or esophageal balloon tamponade.
Prof. Dr. A. Albillos, Servicio de Gastroenterología y Hepatología, Hospital Universitario Ramón y Cajal, M-607, km. 9, 100, 28034 Madrid, Spain,
J Hepatol. 2021;75(2):435–8
Rabinowich L, Grupper A, Baruch R, Ben-Yehoyada M, Halperin T, Turner D, Katchman E, Levi S, Houri I, Lubezky N, Shibolet O, Katchman H
Low immunogenicity to SARS-CoV-2 vaccination among liver transplant recipients
Background and aims: Two SARS-CoV-2 mRNA vaccines were approved to prevent COVID-19 infection, with reported vaccine efficacy of 95%. Liver transplant (LT) recipients are at risk of lower vaccine immunogenicity and were not included in the registration trials. The authors assessed vaccine immunogenicity and safety in this special population.
Methods: LT recipients followed at the Tel-Aviv Sourasky Medical Center and healthy volunteers were tested for SARS-CoV-2 immunoglobulin (Ig)G antibodies directed against the Spike-protein (S) and Nucleocapsid-protein (N) 10–20 days after receiving the second Pfizer-BioNTech BNT162b2 SARS-CoV-2 vaccine dose. Information regarding vaccine side effects and clinical data was collected from patients and medical records.
Results: 80 LT recipients were enrolled. Mean age was 60 years and 30% were female. 25 healthy volunteer controls were younger (mean age 52.7 years, p = 0.013) and mostly female (68%, p = 0.002). All participants were negative for IgG N-protein serology, indicating immunity did not result from prior COVID-19 infection. All controls were positive for IgG S-protein serology. Immunogenicity among LT recipients was significantly lower with positive serology in only 47.5% (p < 0.001). Antibody titer was also significantly lower in this group (mean 95.41 AU/ml vs. 200.5 AU/ml in controls, p < 0.001). Predictors for negative response among LT recipients were older age, lower estimated glomerular filtration rate, and treatment with high-dose steroids and mycophenolate mofetil. No serious adverse events were reported in either group.
Conclusion: Liver transplant recipients developed substantially lower immunological response to the Pfizer-BioNTech SARS-CoV-2 mRNA-based vaccine. Factors influencing serological antibody responses include age, renal function and immunosuppressive medications. The findings require re-evaluation of vaccine regimens in this population.
Dr. L. Rabinowich, Tel-Aviv Sourasky Medical Center, 6 Weizmann Street, Tel-Aviv 6423906, Israel,
Am J Gastroenterol. 2021;116(6):1220–9
Nyssen OP, Perez-Aisa A, Tepes B, Castro-Fernandez M, Kupcinskas J, Jonaitis L, Bujanda L, Lucendo A, Brglez Jurecic N, Perez-Lasala J, Shvets O, Fadeenko G, Huguet JM, Kikec Z, Bordin D, Voynovan I, Leja M, Machado JC, Areia M, Fernandez-Salazar L, Rodrigo L, Alekseenko S, Barrio J, Ortuño J, Perona M, Vologzhanina L, Romero PM, Zaytsev O, Rokkas T, Georgopoulos S, Pellicano R, Buzas GM, Modolell I, Gomez Rodriguez BJ, Simsek I, Simsek C, Roldan Lafuente M, Ilchishina T, Gomez Camarero J, Dominguez-Cajal M, Ntouli V, Dekhnich NN, Phull P, Nuñez O, Lerang F, Venerito M, Heluwaert F, Tonkic A, Caldas M, Puig I, Megraud F, O'Morain C, Gisbert JP; Hp-EuReg Investigators
Adverse event profile during the treatment of Helicobacter pylori: A real-world experience of 22,000 patients from the European Registry on H. pylori management (Hp-EuReg)
Introduction: The safety of Helicobacter pylori eradication treatments and to what extent adverse events (AEs) influence therapeutic compliance in clinical practice are hardly known. The aim of the present study was to assess the frequency, type, intensity, and duration of AEs, and their impact on compliance, for the most frequently used treatments in the "European Registry on Helicobacter pylori management."
Methods: Systematic prospective non-interventional registry of the clinical practice of European gastroenterologists (27 countries, 300 investigators) on the management of H. pylori infection in routine clinical practice. All prescribed eradication treatments and their corresponding safety profile were recorded. AEs were classified depending on the intensity of symptoms as mild/moderate/severe and as serious AEs. All data were subject to quality control.
Results: The different treatments prescribed to 22,492 patients caused at least 1 AE in 23% of the cases; the classic bismuth-based quadruple therapy was the worst tolerated (37% of AEs). Taste disturbance (7%), diarrhea (7%), nausea (6%), and abdominal pain (3%) were the most frequent AEs. The majority of AEs were mild (57%), 6% were severe, and only 0.08% were serious, with an average duration of 7 days. The treatment compliance rate was 97%. Only 1.3% of the patients discontinued treatment due to AEs. Longer treatment durations were significantly associated with a higher incidence of AEs in standard triple, concomitant, bismuth quadruple, and levofloxacin triple or quadruple therapies.
Discussion: Helicobacter pylori eradication treatment frequently induces adverse events, although they are usually mild and of limited duration. Their appearance does not interfere significantly with treatment compliance.
Dr. J.P. Gisbert, Gastroenterology Unit, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Universidad Autónoma de Madrid, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain,
Sun JM, Shen L, Shah MA, Enzinger P, Adenis A, Doi T, Kojima T, Metges JP, Li Z, Kim SB, Cho BC, Mansoor W, Li SH, Sunpaweravong P, Maqueda MA, Goekkurt E, Hara H, Antunes L, Fountzilas C, Tsuji A, Castro Oliden V, Liu Q, Shah S, Bhagia P, Kato K; KEYNOTE-590 Investigators
Pembrolizumab plus chemotherapy versus chemotherapy alone for first-line treatment of advanced esophageal cancer (KEYNOTE-590): A randomized, placebo-controlled, phase 3 study
Background: First-line therapy for advanced esophageal cancer is currently limited to fluoropyrimidine plus platinum-based chemotherapy. The authors aimed to evaluate the anti-tumor activity of pembrolizumab plus chemotherapy versus chemotherapy alone as first-line treatment in advanced esophageal cancer and Siewert type 1 gastro-esophageal junction cancer.
Methods: They did a randomized, placebo-controlled, double-blind, phase 3 study across 168 medical centers in 26 countries. Patients aged 18 years or older with previously untreated, histologically or cytologically confirmed, locally advanced, unresectable or metastatic esophageal cancer or Siewert type 1 gastroesophageal junction cancer (regardless of PD-L1 status), measurable disease per Response Evaluation Criteria in Solid Tumors version 1.1, and Eastern Cooperative Oncology Group performance status of 0–1, were randomly assigned (1:1) to intravenous pembrolizumab 200 mg or placebo, plus 5-fluorouracil and cisplatin (chemotherapy), once every 3 weeks for up to 35 cycles. Randomization was stratified by geographical region, histology, and performance status. Patients, investigators, and site staff were masked to group assignment and PD-L1 biomarker status. Primary end points were overall survival (OS) in patients with esophageal squamous cell carcinoma (ESCC) and PD-L1-combined positive score (CPS) ≥ 10, and OS and progression-free survival (PFS) in patients with ESCC, PD-L1 CPS ≥ 10, and in all randomized patients.
Findings: Between July 25, 2017, and June 3, 2019, 1020 patients were screened and 749 were enrolled and randomly assigned to pembrolizumab plus chemotherapy (n = 373 [50%]) or placebo plus chemotherapy (n = 376 [50%]). At the first interim analysis (median follow-up of 22.6 months), pembrolizumab plus chemotherapy was superior to placebo plus chemotherapy for OS in patients with ESCC and PD-L1 CPS ≥ 10 (median 13.9 months vs. 8.8 months; hazard ratio [HR = 0.57, 95% confidence interval [CI]: 0.43–0.75; p < 0.0001), ESCC (12.6 months vs. 9.8 months; HR = 0.72, 95% CI: 0.60–0.88; p = 0.0006), PD-L1 CPS ≥ 10 (13.5 months vs. 9.4 months; HR = 0.62, 95% CI: 0.49–0.78; p < 0.0001), and in all randomized patients (12.4 months vs. 9.8 months; HR = 0.73, 95% CI: 0.62–0.86; p < 0.0001). Pembrolizumab plus chemotherapy was superior to placebo plus chemotherapy for PFS in patients with ESCC (6.3 months vs. 5.8 months; HR = 0.65, 95% CI: 0.54–0.78; p < 0.0001), PD-L1 CPS ≥ 10 (7.5 months vs. 5.5 months; HR = 0.51, 95% CI: 0.41–0.65; p < 0.0001), and in all randomized patients (6.3 months vs. 5.8 months; HR = 0.65, 95% CI: 0.55–0.76; p < 0.0001). Treatment-related adverse events of grade 3 or higher occurred in 266 (72%) patients in the pembrolizumab plus chemotherapy group versus 250 (68%) in the placebo plus chemotherapy group.
Interpretation: Compared with placebo plus chemotherapy, pembrolizumab plus chemotherapy improved overall survival in patients with previously untreated, advanced esophageal squamous cell carcinoma (ESCC) and PD-L1 CPS ≥ 10, and overall survival and progression-free survival in patients with ESCC, PD-L1 CPS ≥ 10, and in all randomized patients regardless of histology, and had a manageable safety profile in the total as-treated population.
Prof. Dr. J.-M. Sun, Samsung Medical Center, Sungkyunkwan University, 25-2 Sungkyunkwan-ro, Myeongnyun 3(sam)ga-dong, Jongno-gu, Seoul 06351, South Korea,
Am J Gastroenterol. 2021;116(9):1868–75
Thosani N, Rashtak S, Kannadath BS, Munjal A, Meriwether M, Yoon ED, Hermann A, Ali S, Haddad PG, Patil P, Ramireddy S, Badillo R, DaVee RT, Guha S
Bleeding risk and mortality associated with uninterrupted antithrombotic therapy during percutaneous endoscopic gastrostomy tube placement
Introduction: Antithrombotic therapy is often interrupted before the placement of a percutaneous endoscopic gastrostomy (PEG) tube because of potentially increased risk of hemorrhagic events. The aim of the present study was to evaluate the risk of bleeding events and overall complication rates after PEG in patients on uninterrupted antiplatelet and anticoagulation therapy in a high-volume center.
Methods: Data regarding demographics, diagnoses, comorbidities, and clinical outcomes pertinent to PEG were collected from 2010 to 2016. Furthermore, data regarding antithrombotic therapy along with the rate of minor or major complications including bleeding associated with this procedure were analyzed. Significant bleeding was defined as postprocedure bleeding from PEG site requiring a blood transfusion and/or surgical/endoscopic intervention.
Results: The authors included 1613 consecutive PEG procedures in this study, of which 1540 patients (95.5%) received some form of uninterrupted antithrombotic therapy. Of those patients, 535 (34.7%) were on aspirin, 256 (16.6%) on clopidogrel, and 119 (7.7%) on both aspirin and clopidogrel. Subcutaneous heparin was uninterrupted in 980 (63.6%), intravenous heparin in 34 (2.1%), warfarin in 168 (10.9%), and direct-acting oral anticoagulation in 82 (5.3%) patients who overlapped on multiple drugs. Six significant bleeding events were observed in the entire cohort (0.39%), and all were in subcutaneous heparin groups either alone or in combination with aspirin. No clinically significant bleeding was noted in patients on uninterrupted aspirin, warfarin, clopidogrel, or direct-acting oral anticoagulation groups. Only 5 patients (0.31%) had PEG-related mortality.
Discussion: The risk of significant bleeding associated with the percutaneous endoscopic gastrostomy tube placement was minimal in patients on uninterrupted periprocedural antithrombotic therapy.
S. Guha, M.D., Ph.D., Professor of Medicine, Division of Gastroenterology, Hepatology, and Nutrition, Department of Internal Medicine, McGovern Medical School at UTHealth, 6410 Fannin Street #1014, Houston, TX77030, USA,
Crinò SF, Di Mitri R, Nguyen NQ, Tarantino I, de Nucci G, Deprez PH, Carrara S, Kitano M, Shami VM, Fernández-Esparrach G, Poley JW, Baldaque-Silva F, Itoi T, Manfrin E, Bernardoni L, Gabbrielli A, Conte E, Unti E, Naidu J, Ruszkiewicz A, Amata M, Liotta R, Manes G, Di Nuovo F, Borbath I, Komuta M, Lamonaca L, Rahal D, Hatamaru K, Itonaga M, Rizzatti G, Costamagna G, Inzani F, Curatolo M, Strand DS, Wang AY, Ginès À, Sendino O, Signoretti M, van Driel LMJW, Dolapcsiev K, Matsunami Y, van der Merwe S, van Malenstein H, Locatelli F, Correale L, Scarpa A, Larghi A
Endoscopic ultrasound-guided fine-needle biopsy with or without rapid on-site evaluation for diagnosis of solid pancreatic lesions: A randomized controlled non-inferiority trial
Background and aims: The benefit of rapid on-site evaluation (ROSE) on the diagnostic accuracy of endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) has never been evaluated in a randomized study. This trial aimed to test the hypothesis that in solid pancreatic lesions (SPLs), diagnostic accuracy of EUS-FNB without ROSE was not inferior to that of EUS-FNB with ROSE.
Methods: A non-inferiority study (non-inferiority margin, 5%) was conducted at 14 centers in 8 countries. Patients with SPLs requiring tissue sampling were randomly assigned (1:1) to undergo EUS-FNB with or without ROSE using new-generation FNB needles. The touch-imprint cytology technique was used to perform ROSE. The primary end point was diagnostic accuracy, and secondary end points were safety, tissue core procurement, specimen quality, and sampling procedural time.
Results: 800 patients were randomized over an 18-month period, and 771 were analyzed (385 with ROSE and 386 without). Comparable diagnostic accuracies were obtained in both arms (96.4% with ROSE and 97.4% without ROSE; p = 0.396). Non-inferiority of EUS-FNB without ROSE was confirmed with an absolute risk difference of 1.0% (1-sided 90% confidence interval, -1.1–3.1%; non-inferiority p < 0.001). Safety and sample quality of histologic specimens were similar in both groups. A significantly higher tissue core rate was obtained by EUS-FNB without ROSE (70.7% vs. 78.0%; p = 0.021), with a significantly shorter mean sampling procedural time (17.9 ± 8.8 vs. 11.7 ± 6.0 minutes; p < 0.0001).
Conclusions: Endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) demonstrated high diagnostic accuracy in evaluating solid pancreatic lesions independently on execution of rapid on-site evaluation (ROSE). When new-generation FNB needles are used, ROSE should not be routinely recommended.
Dr. S.F. Crinò, Department of Medicine, Gastroenterology and Digestive Endoscopy Unit, The Pancreas Institute, University Hospital of Verona, P.le L.A. Scuro 10, 37134 Verona, Italy,