Intraductal fully covered self-expandable metal stent versus multiple plastic stents for treating biliary anastomotic strictures after liver transplantation

Background and aims: Fully covered metal stents (FCSEMSs) are increasingly used for treatment of biliary anastomotic strictures (ASs) after liver transplantation (LT), requiring fewer endoscopic interventions than does treatment with multiple plastic stents (MPSs). Previous studies, however, have reported adverse events such as stent migration and pancreatitis. The intraductal FCSEMS (ID-FCSEMS) potentially avoids these disadvantages. This study aimed to assess the efficacy and safety of ID-FCSEMSs compared with MPSs for AS. Methods: The cohorts of LT patients treated for AS with endoscopic stenting between 2010 and 2019 from 2 Dutch liver transplantation centers were retrospectively analyzed. Patients treated with ID-FCSEMSs or MPSs were included. Results: 80 patients (44 with ID-FCSEMSs vs 36 with MPSs) were included, with a median follow-up time of 52 versus 64 months (P = .183). Stricture resolution was 93% in the ID-FCSEMS versus 97% in the MPS group (P = 1.000) after a median of 19 and 26 weeks, respectively (P = .031). The median number of ERCPs was 2 in the ID-FCSEMS group versus 4 in the MPS group (P &lt; .001). Stricture recurrence occurred in 33% of ID-FCSEMS versus 29% of MPS patients (P = .653) after a median of 24 and 55 weeks (P = .403). Stent migration occurred in 16% of ID-FCSEMS versus 39% of MPS patients (P = .020). Post-ERCP fever was observed in 34% of ID-FCSEMS patients compared with 14% of MPS patients (P = .038). No significant differences were found in pancreatitis rate between the groups, being 6.8% for ID-FCSEMSs and 5.6% for MPSs (P = .816). Conclusion: ID-FCSEMSs for the treatment of AS after LT provides similar stricture resolution and recurrence rates as MPSs, though with a significant reduction of procedures needed.</p

Randomized Trial of Ciclosporin with 2-h Monitoring vs. Tacrolimus with Trough Monitoring in Liver Transplantation:DELTA Study

Background and Aims: Previous trials comparing cyclosporine and tacrolimus after liver transplantation (LT) showed conflicting results. Most used trough monitoring for cyclosporine (C0), leading to less accurate dosing than with 2-h monitoring (C2). Only one larger trial compared C2 with tacrolimus based on trough level (T0) after LT, with similar treated biopsy-proven acute rejection (tBPAR) and graft loss, while a smaller trial had less tBPAR with C2 compared to T0. Therefore, it is still unclear which calcineurin inhibitor is preferred after LT. We aimed to demonstrate superior efficacy (tBPAR), tolerability, and safety of C2 or T0 after first LT. Methods: Patients after first LT were randomized to C2 or T0. tBPAR, patient-and graft survival, safety and tolerability were the main endpoints, with analysis by Fisher test, Kaplan–Meier survival analysis and log-rank test. Results: In intention-to treat analysis 84 patients on C2 and 85 on T0 were included. Cumulative incidence of tBPAR C2 vs. T0 was 17.7% vs. 8.4% at 3 months (p=0.104), and 21.9% vs. 9.7% at 6 and 12 months (p=0.049). One-year cumulative mortality C2 vs. T0 was 15.5% vs. 5.9% (p=0.049) and graft loss 23.8% vs. 9.4% (p=0.015). Serum triglyceride and LDL-cholesterol was lower with T0 than with C2. Incidence of diarrhea in T0 vs, C2 was 64% vs. 31% (p≤0.001), with no other differences in safety and tolerability. Conclusions: In the first year after LT immunosuppression with T0 leads to less tBPAR and better patient-/re-transplant-free survival as compared to C2.</p

Role of endoscopic ultrasonography in the diagnostic work-up of idiopathic acute pancreatitis (PICUS):study protocol for a nationwide prospective cohort study

INTRODUCTION: Idiopathic acute pancreatitis (IAP) remains a dilemma for physicians as it is uncertain whether patients with IAP may actually have an occult aetiology. It is unclear to what extent additional diagnostic modalities such as endoscopic ultrasonography (EUS) are warranted after a first episode of IAP in order to uncover this aetiology. Failure to timely determine treatable aetiologies delays appropriate treatment and might subsequently cause recurrence of acute pancreatitis. Therefore, the aim of the Pancreatitis of Idiopathic origin: Clinical added value of endoscopic UltraSonography (PICUS) Study is to determine the value of routine EUS in determining the aetiology of pancreatitis in patients with a first episode of IAP. METHODS AND ANALYSIS: PICUS is designed as a multicentre prospective cohort study of 106 patients with a first episode of IAP after complete standard diagnostic work-up, in whom a diagnostic EUS will be performed. Standard diagnostic work-up will include a complete personal and family history, laboratory tests including serum alanine aminotransferase, calcium and triglyceride levels and imaging by transabdominal ultrasound, magnetic resonance imaging or magnetic resonance cholangiopancreaticography after clinical recovery from the acute pancreatitis episode. The primary outcome measure is detection of aetiology by EUS. Secondary outcome measures include pancreatitis recurrence rate, severity of recurrent pancreatitis, readmission, additional interventions, complications, length of hospital stay, quality of life, mortality and costs, during a follow-up period of 12 months. ETHICS AND DISSEMINATION: PICUS is conducted according to the Declaration of Helsinki and Guideline for Good Clinical Practice. Five medical ethics review committees assessed PICUS (Medical Ethics Review Committee of Academic Medical Center, University Medical Center Utrecht, Radboud University Medical Center, Erasmus Medical Center and Maastricht University Medical Center). The results will be submitted for publication in an international peer-reviewed journal. TRIAL REGISTRATION NUMBER: Netherlands Trial Registry (NL7066). Prospectively registered

Randomized Trial of Ciclosporin with 2-h Monitoring vs. Tacrolimus with Trough Monitoring in Liver Transplantation:DELTA Study

Background and Aims: Previous trials comparing cyclosporine and tacrolimus after liver transplantation (LT) showed conflicting results. Most used trough monitoring for cyclosporine (C0), leading to less accurate dosing than with 2-h monitoring (C2). Only one larger trial compared C2 with tacrolimus based on trough level (T0) after LT, with similar treated biopsy-proven acute rejection (tBPAR) and graft loss, while a smaller trial had less tBPAR with C2 compared to T0. Therefore, it is still unclear which calcineurin inhibitor is preferred after LT. We aimed to demonstrate superior efficacy (tBPAR), tolerability, and safety of C2 or T0 after first LT. Methods: Patients after first LT were randomized to C2 or T0. tBPAR, patient-and graft survival, safety and tolerability were the main endpoints, with analysis by Fisher test, Kaplan–Meier survival analysis and log-rank test. Results: In intention-to treat analysis 84 patients on C2 and 85 on T0 were included. Cumulative incidence of tBPAR C2 vs. T0 was 17.7% vs. 8.4% at 3 months (p=0.104), and 21.9% vs. 9.7% at 6 and 12 months (p=0.049). One-year cumulative mortality C2 vs. T0 was 15.5% vs. 5.9% (p=0.049) and graft loss 23.8% vs. 9.4% (p=0.015). Serum triglyceride and LDL-cholesterol was lower with T0 than with C2. Incidence of diarrhea in T0 vs, C2 was 64% vs. 31% (p≤0.001), with no other differences in safety and tolerability. Conclusions: In the first year after LT immunosuppression with T0 leads to less tBPAR and better patient-/re-transplant-free survival as compared to C2.</p

The performance and safety of motorized spiral enteroscopy, including in patients with surgically altered gastrointestinal anatomy: A multicenter prospective study

Background: Data are scarce on the efficacy and safety of motorized spiral enteroscopy (MSE). No data are available on the utility of this technique in patients with surgically altered gastrointestinal (GI) anatomy. We aimed to evaluate the safety and efficacy of MSE in patients with suspected small-bowel disease, including those with surgically altered GI anatomy. Methods: A multicenter prospective observational, uncontrolled study evaluated MSE in consecutive patients with suspected small-bowel pathology and an indication for diagnostic and/or therapeutic intervention. Results: A total of 170 patients (102 men; median age 64 years, range 18 89) were included. The overall diagnostic yield was 64.1%. Endotherapy was performed in 53.5% of procedures. The median total procedure times for the antegrade and retrograde approaches were 45 minutes (interquartile range [IQR] 30 80) and 40 minutes (IQR 30 70), respectively. When total (pan)enteroscopy was intended, this was achieved at rate of 70.3% (28.1% by antegrade approach and 42.2% by a bidirectional approach). Surgically altered GI anatomy was present in 34 /170 of all procedures (20.0%) and in 11 /45 of the successful total enteroscopy procedures (24.4%). Propofol sedation or general anesthesia were used in 92.9% and 7.1% of the procedures, respectively. Minor adverse events were observed in 15.9% of patients, but there were no major adverse events. Conclusion: MSE seems to be an effective and safe endoscopic procedure. Total (pan)enteroscopy can be achieved, in one or two sessions, even in the presence of surgically altered GI anatomy. The total procedure time is relatively short. For both antegrade and retrograde MSE procedures, propofol sedation seems sufficient and safe

Motorized Spiral Enteroscopy: Multicenter prospective study on performance and safety including in patients with surgically-altered gastrointestinal anatomy

BACKGROUND AND STUDY AIMS: Data are scarce on the efficacy and safety of the Motorized spiral enteroscopy (MSE). No data are available on the utility of this technique in patients with surgically-altered gastrointestinal (GI) anatomy. We aimed to evaluate the safety and efficacy of MSE in patients with suspected small-bowel disease including those with surgically-altered GI anatomy. METHODS: A multicenter prospective observational, uncontrolled study evaluated MSE in consecutive patients with suspected small-bowel pathology indicated for diagnostic and/or therapeutic intervention. RESULTS: A total of 170 patients (median age, 64 years; range 18-89 years; 102 male, 68 female) were included. The overall diagnostic yield was 64.1%. Endotherapy was performed in 53.5% of procedures. The median total procedure time for antegrade and retrograde approach was 45 minutes (IQR=30-80) and 40 (IQR=30-70) respectively. When total (pan-)enteroscopy was intended, this was achieved at rate of 70.3%, (28.1% by antegrade approach and 42.1% by a bi-directional approach). Surgically-altered GI anatomy was present in 34/170 (20%) of the all procedures and in 11/45 (24.4%) of the successful total enteroscopy procedures. Propofol sedation or general anesthesia were used in 92.9% and 7% of the procedures respectively. Minor adverse events were observed in 15.8% of patients, but no major adverse events. CONCLUSION: MSE seems to be effective and safe endoscopic procedure. Total (pan-)enteroscopy can be achieved, in one or two sessions, even in the presence of surgically-altered GI anatomy. The total procedure time is relatively short. For both antegrade and retrograde MSE procedures, propofol sedation seems sufficient and safe

Impact of EUS in liver transplantation workup for patients with unresectable perihilar cholangiocarcinoma

Background and Aims: For a highly selected group of patients with unresectable perihilar cholangiocarcinoma (pCCA), liver transplantation (LT) is a treatment option. The Dutch screening protocol comprises nonregional lymph node (LN) assessment by EUS, and whenever LN metastases are identified, further LT screening is precluded. The aim of this study is to investigate the yield of EUS in patients with pCCA who are potentially eligible for LT. Methods: In this retrospective, nationwide cohort study, all consecutive patients with suspected unresectable pCCA who underwent EUS in the screening protocol for LT were included from 2011 to 2021. During EUS, sampling of a “suspicious” nonregional LN was performed based on the endoscopist's discretion. The primary outcome was the added value of EUS, defined as the number of patients who were precluded from further screening because of malignant LNs. Results: A total of 75 patients were included in whom 84 EUS procedures were performed, with EUS-guided tissue acquisition confirming malignancy in LNs in 3 of 75 (4%) patients. In the 43 who underwent surgical staging according to the protocol, nonregional LNs with malignancy were identified in 6 (14%) patients. Positive regional LNs were found in 7 patients in post-LT-resected specimens. Conclusions: Our current EUS screening for the detection of malignant LNs in patients with pCCA eligible for LT shows a limited but clinically important yield. EUS with systematic screening of all LN stations, both regional and nonregional, and the sampling of suspicious lymph nodes according to defined and set criteria could potentially increase this yield.</p

High peak alanine aminotransferase determines extra risk for nonanastomotic biliary strictures after liver transplantation with donation after circulatory death

Orthotopic liver transplantation (OLT) with donation after circulatory death (DCD) often leads to a higher first week peak alanine aminotransferase (ALT) and a higher rate of biliary nonanastomotic strictures (NAS) as compared to donation after brain death (DBD). This retrospective study was to evaluate whether an association exists between peak ALT and the development of NAS in OLT with livers from DBD (n=399) or DCD (n=97) from two transplantation centers. Optimal cutoff value of peak ALT for risk of development of NAS post-DCD-OLT was 1300IU/l. The 4-year cumulative incidence of NAS after DCD-OLT was 49.5% in patients with a high ALT peak post-OLT, compared with 11.3% in patients with a low ALT peak. (

Risk of multiple pancreatic cancers in CDKN2A-p16-Leiden mutation carriers

CDKN2A-p16-Leiden mutation carriers have a substantial risk of developing pancreatic ductal adenocarcinoma (PDAC). One of the main clinical features of hereditary cancer is the development of multiple cancers. Since 2000, we have run a surveillance program for CDKN2A-p16-Leiden mutation carriers. The patients are offered a yearly MRI with optionally endoscopic ultrasound. In patients with a confirmed lesion, usually, a partial resection of the pancreas is recommended. A total of 18 PDAC (8.3%) were detected in 218 mutation carriers. In this report, we describe two CDKN2A-p16-Leiden patients with a synchronous and metachronous PDAC. Including two previously-reported cases, we identified four patients with multiple PDAC: two of 18 patients within the surveillance program (11%) and two patients with a proven CDKN2A-p16-Leiden mutation not participating in the surveillance program. In conclusion, this study demonstrated a high risk of developing multiple PDAC in CDKN2A-p16-Leiden mutation carriers. After detecting a primary tumor, it is very important to exclude the presence of a second synchronous tumor. Moreover, after a partial pancreatectomy for PDAC, close surveillance is necessary. In view of the current findings, offering a total pancreatectomy might be an appropriate option in patients with an early PDAC