Introduction

Therapeutic management of acute biliary pancreatitis (ABP) includes endoscopic sphincterotomy and cholecystectomy. However, the optimal feeding strategy prior to cholecystectomy—early oral intake or exclusive enteral nutrition—remains debated, particularly given the risk of recurrent biliary events (BEs) before surgery, especially when surgery is delayed.

Aims & Methods

The primary objective was to evaluate the likehood of BEs (biliary colic/migration, stone impaction, cholangitis, recurrent acute pancreatitis, and acute cholecystitis) prior to cholecystectomy, comparing feeding methods: oral vs. exclusive enteral nutrition. The secondary objective was to evaluate cholecystectomy rates during the initial hospitalization and the reasons for non-performance. Data were collected during hospitalization, at 3 months, and at 6 months if surgery had not been performed by month 3. BEs and feeding modalities at those times were documented. Analyses included Cox models and Chi-square tests.

Results

From October 2022 to December 2023, 1,172 patients with ABP were prospectively enrolled by 60 French hospitals, with 1,167 included in the final analysis. Sixty patients (5%) were lost to follow-up, and 34 deaths (3%) were reported. Severe ABP was observed in 27.2% (n=317) of patients. After 48–72 hours, oral feeding was resumed in 62% (n=724), enteral feeding in 16% (n=192), and fasting/parenteral feeding in 21% (n=249). During follow-up, 236 BEs occurred in 172 patients, meaning 15.5% experienced at least one event, with a median onset time of 26 days (range: 9–57 days). Specifically, 6% had at least one episode of biliary colic/migration, 2.1% experienced stone impaction, 2.3% developed cholangitis, 6.1% had recurrent AP (9% of which were severe), and 1.6% developed acute cholecystitis.
Univariate analysis identified several factors associated with a higher risk of BE recurrence (p < 0.10): age ≥52 years (p=0.093), obesity (BMI ≥30, p=0.032), ASA score >2 (p=0.097), total bilirubin ≥60 µmol/L (p=0.010), CRP >150 mg/L, diagnostic delay ≥21 days (p=0.009), and prior sphincterotomy (p=0.136). No difference in BE incidence was observed between severe and non-severe ABP (p=0.497) when analyzing the first 172 BEs.
Over the full follow-up period, despite the 87 BEs analyzed and potential biases, there remained no significant association between nutrition type (oral vs. exclusive enteral nutrition ) and the likelihood of BE occurrence (p=0.447).
In patients with non-severe ABP, cholecystectomy was performed during the initial hospitalization in only 33% of cases. The main reasons for non-performance were structural (e.g., lack of availability or surgeon refusal), accounting for 45% of cases.

Conclusion

BEs are frequent and clinically relevant: 15.5% of patients experienced at least one before surgery, with 6% developing recurrent ABP (9% of which were severe). Cholecystectomy remains underutilized; only one-third of patients with non-severe ABP underwent it during their initial stay, often due to modifiable reasons. Neither ABP severity nor nutritional type-oral vs enteral nutrition (despite potential biases, missing data, and ongoing analysis)-appeared to be associated with the occurrence of BEs prior to surgery. Early cholecystectomy, when possible, remains the only reliable strategy for preventing BEs.

Disclosure

This study received a research grant from Fresenius Kabi.

Introduction

One in four patients experiencing a first episode of non-gallstone-related acute pancreatitis (AP) will develop recurrent disease. Recurrent episodes of AP or acute-on-chronic pancreatitis (CP) lead to decreased quality of life and disease progression. Aside from addressing the underlying cause of pancreatitis (which is sometimes impossible), effective measures to prevent recurrence are lacking. Meta-analyses of randomized controlled trials and epidemiological and cohort studies indicate that statins may provide protection against the development of initial AP.

Aims & Methods

The SIMBA study is a triple-blind, randomized, placebo-controlled, parallel-group multicenter trial. Patients with non-biliary recurrent acute pancreatitis (AP) or acute flares of chronic pancreatitis (CP) (at least two episodes in the last 12 months) were randomized to receive either simvastatin 40 mg daily or a placebo and followed up for 1 year. The sample size was calculated to be 144 patients, but slow recruitment prompted an interim analysis. The primary aim was to compare the recurrence of AP or acute flares in CP (RAP/AF).

Results

Eighty-three patients were included from 22 centers from Spain and 1 from India. The median age was 54 years, and 49 (59%) were men. Sixty-one (73.5%) patients had AP and 22 (26.5%) CP. Thirty-nine (47%) patients received placebo and 44 (53%) simvastatin. The median follow-up was 262 months. During follow-up, there were 12 (30.8%) RAP/AF in the placebo group and 15 (34.1%) in the simvastatin group (p 0.747, intention-to-treat analysis). Nor were there significant differences in the Kaplan-Meier curve (p=0.543). These results did not change when analyzing the patients who had finished treatment (per-protocol analysis) or when analyzing AP and CP separately.

Conclusion

Simvastatin does not appear to protect against recurrent episodes of acute pancreatitis or acute-on-chronic pancreatitis.

Introduction

Gastric outlet obstruction is a common manifestation of advanced gastric, duodenal, and periampullary malignancies, severely affecting quality of life. Endoscopic ultrasonography-guided gastroenterostomy (EUS-GE) may be superior to surgical gastroenterostomy (SGJ) as palliative treatment for this condition, but randomised trials are currently lacking.

Aims & Methods

We performed a multicenter, randomized controlled trial involving palliative patients with a malignant obstruction localized between the pylorus and the distal duodenum, randomizing them 1:1 to either EUS-GE or SGJ. The first co-primary superiority end point was time to solid oral intake. The second co-primary non-inferiority end point was persistent or recurrent obstructive symptoms for which a reintervention was required within six months after treatment. The predefined non-inferiority margin was 20%.

Results

From February 2022 to February 2024, 250 patients were screened in 12 participating hospitals in the Netherlands. Of the 98 enrolled patients, 48 were assigned to EUS-GE and 50 were assigned to SGJ. Median age was 69 versus 70 years and the most prevalent etiology was pancreatic cancer in 58% versus 50% in the EUS-GE group and SGJ group, respectively. Median time to oral intake was significantly shorter in the EUS-GE group compared to the SGJ group: 1 day versus 3 days (hazard ratio, 2.21, 95% CI, 1.43 to 3.42, p=0.0003). In the endoscopic group, 5 patients (10%) experienced persistent or recurrent obstructive symptoms requiring reintervention, compared with 6 patients (12%) in the surgical group (risk difference, 1.6%, upper limit of 90% CI, 8.9%). Clinical success, defined as the ability to tolerate solid oral intake, was higher in the EUS-GE group (96% versus 80%, relative risk, 1.20, 95% CI, 1.03 to 1.39). Median length of hospital stay was shorter in the EUS-GE group (1 day versus 4 days, relative change, 0.46, 95% CI, 0.20 to 0.78). Serious adverse events, defined as Clavien-Dindo ≥3B, were observed in 8% of patients in the EUS-GE group and in 12% of patients in the SGJ group (relative risk, 0.69, 95% CI, 0.21 to 2.31). Median survival was 91 days after EUS-GE (95% CI, 74 to 140) and 74 days (95% CI, 46 to 110) after SGJ. Thirty-day mortality was 13% in the EUS-GE group and 26% in the SGJ group (relative risk, 0.48, 95% CI, 0.20 to 1.14). In the first three months following the procedure, quality of life was not different between the two treatments.

Conclusion

This trial showed that EUS-GE, compared to SGJ, is superior in terms of time to solid oral intake and non-inferior with regards to the rate of persistent or recurrent obstructive symptoms requiring reintervention. Based on these results, EUS-GE should be the preferred palliative treatment for malignant gastric outlet obstruction.

Disclosure

Yorick L. van de Pavert, Janine B. Kastelijn, Marc G. Besselink, Dieke C. Booij, Jurjen J. Boonstra, Judith Boot, Olivier R.C. Busch, Wouter J.M. Derksen, Bas Groot Koerkamp, Akin Inderson, Wim J. Lammers, Daan J. Lips, J. Sven D. Mieog, I. Quintus Molenaar, Alexander A.F.A. Veenhof, Niels G. Venneman, Robert C. Verdonk, Paco M.J. Welsing, Thomas R. de Wijkerslooth, and Hjalmar C. van Santvoort report no conflicts of interest.
Freek Daams is proctor for Intuitive, received educational grants from Medtronic, and received speaker’s fees from Johnson & Johnson and Medtronic.
Paul Fockens is consultant for Cook Endoscopy and Olympus.
Rogier P. Voermans reports research grants from Boston Scientific and Prion Medical, performed as a consultant for Boston Scientific and Cook Medical, and received speaker’s fees from Mylan and Zambon.
Roy L.J. van Wanrooij is a consultant for Boston Scientific.
Marco J. Bruno is a consultant for Boston Scientific, Cook Medical, and Pentax Medical; received support for industry-initiated studies from Boston Scientific and Cook Medical; and received support for investigator-initiated studies from Boston Scientific, Cook Medical, Pentax Medical, Mylan, Interscope, and ChiRhoStim.
Jeanin E. van Hooft received lecture fees from Cook Medical, Boston Scientific, Medtronic, and Abbvie, is an independent observer for Olympus, and is the current secretary general of the federation United European Gastroenterology (UEG).
Leon M.G. Moons is a consultant for Boston Scientific.
Frank P. Vleggaar is a consultant for Boston Scientific.