A RANDOMIZED TRIAL OF ENDOSCOPIC ULTRASOUND GUIDED CELIAC PLEXUS NEUROLYSIS WITH ALCOHOL ALONE VS ALCOHOL+ BUPIVACAINE: PRELIMINARY RESULTS

Background and Aims
Surgical resection is a standard treatment option for management of pancreatic cysts. The newly introduced EUS-guided ethanol ablation (EUS-ablation) has been performed as an alternative to pancreatectomy in selected patients and is expected to reduce the high rates of short-and long-term morbidity of pancreatectomy. However, no comparative studies have been carried out between EUS-ablation and pancreatectomy for pancreatic cysts.
Methods
We reviewed the prospectively collected pancreatic cyst database to analyze consecutive patients with unilocular or oligolocular pancreatic cysts requiring treatment who underwent EUS-ablation or pancreatectomy between January 2015 and July 2021. After excluding cases in which malignancies were suspected preoperatively, we performed 1:1 match using propensity score matching based on age, gender, cyst size, cyst morphology (unilocular or oligolocular), cyst location, and American Society of Anesthesiologists (ASA) physical status classification between EUS-ablation and pancreatectomy. Complete remission rates, adverse events, mortality, and occurrence of diabetes were evaluated.
Results
A total of 620 patients (310 EUS-ablation, 310 pancreatectomy) were selected after propensity score matching. During follow-up, rate of complete resolution of pancreatic cysts was lower in EUS-ablation group (77% vs. 100%; P = 0.001). However, the EUS-ablation group showed lower rates of early adverse events (EUS-ablation, 12.6% vs. pancreatectomy, 46.5%; P = 0.001), late adverse events (1% vs. 16%; P = 0.001), occurrence of diabetes (0% vs. 18%; P = 0.001), unplanned readmissions (1% vs. 15%; P = 0.001), and cumulative morbidities at 5 years (11.3% vs. 37.5%; P = 0.001) than did the pancreatectomy group. There were significant differences in the severity of the adverse events: mild (10% vs. 16%; P = 0.018); moderate (2% vs. 15%; P = 0.001); severe (0% vs. 3%; P = 0.004). The EUS-ablation group required interventions for adverse events less frequently than the pancreatectomy group did (1% vs. 10%; P = 0.001). Procedure or surgery-related mortality rates in EUS-ablation group and pancreatectomy group was 0% and 0.3%, respectively.
Conclusions
In management of unilocular or oligolocular pancreatic cyst, EUS-guided ethanol ablation might be a good alternative to pancreatectomy in selected patients regarding morbidity and mortality benefits.

Aims
Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) is emerging as safe and effective treatment for pancreatic neoplasms. We aimed to compare EUS-RFA and surgical resection for the treatment of pancreatic insulinoma (PI).

Methods
Patients with non-metastatic PI who underwent EUS-RFA at 23 centers or surgical resection at eight high-volume pancreatic surgery institutions between 2014 and 2022 were identified and outcomes compared using a propensity-matching analysis. Patients with multiple nodules or diagnosed with MEN-1 were excluded. Primary outcome was safety. Adverse events (AEs) were defined according to international definitions and graded using the AGREE and Clavien-Dindo classifications. Secondary outcomes were treatment effectiveness, length of hospital stay, and rate of recurrence with need of additional treatment after EUS-RFA. Treatment effectiveness was defined as complete disappearance of symptoms related to insulin secretion and was assessed including possible multiple treatments in the EUS-RFA group.

Results
Overall, 328 patients were identified and 304 were included (111 EUS-RFA and 193 surgical resections). Using propensity score matching, 178 patients were selected and 89 allocated in each group (1:1). The two groups were evenly distributed in terms of age, sex, Charlson comorbidity index, ASA score, BMI, distance between lesion and main pancreatic duct, lesion site, size, and grade (Figure 1). Lesions were in the head, body, or tail in 69 (38.8%), 66 (37.1%), and 43 (24.1%) cases, respectively. Mean lesion size was 13.5 ± 4.8mm. Tumor grading was G1 in 145 (81.5%) cases, G2 in 13 (7.3%), and remained unknown in 20 (11.2%) cases. The rate of AEs was 18.0% and 61.8% after EUS-RFA and surgical resection, respectively (p<0.001). The most common AEs was pancreatic fistula in the surgical group (42.7%) and acute pancreatitis in the EUS-RFA group (10.1%) (Figure 2). No severe (AGREE ≥3) AEs were observed in the EUS-RFA group compared with 7.8% after surgery (p=0.0002). Clinical efficacy was 100% after surgery and 95.5% after EUS-RFA (p=0.160). However, the mean duration of follow-up time was shorter in the EUS-RFA group (median 23 (IQR 14-31) vs 37 (IQR 17.5-67) months, p<0.0001). Hospital stay was significantly longer in the surgical group (11.1 ± 9.7 vs 3.0 ± 2.5 days in the EUS-RFA group, p<0.0001). Fifteen (16.9%) lesions recurred after EUS-RFA after a mean time of 9.5 months, and uneventfully underwent to second EUS-RFA (n=11) or surgical resection (n=4). No distant/nodal metastases appeared during follow-up.

Conclusion
EUS-RFA is safer than surgery and highly effective for the treatment of PI. When a lesion recurs after EUS-RFA it can be safely managed with a second EUS-RFA treatment or surgical resection. If confirmed in a randomized study, EUS-RFA could be suggested as first-line therapy for sporadic PI.

Background and aims:
Pain often complicates pancreatic cancer management. EUS-CPN is usually performed using dehydrated alcohol and bupivacaine. We hypothesized that alcohol dilution by bupivacaine reduces the alcohol-induced neurolysis and subsequent pain relief, with no impact on periprocedural pain. We therefore undertook a randomized trial of EUS-guided CPN with alcohol alone vs alcohol + bupivacaine. These are interim results from our ongoing non-inferiority trial and were requested by our data safety monitoring board. The study was approved by research ethics board with approval number of 2022-9969, 21.151 and registered on clinicaltrial.gov; registration number NCT04951804.

Methods:
Patients with inoperable painful pancreatic body cancer were randomised by sealed envelope to bilateral EUS-CPN with alcohol (10cc x 2) or alcohol (10ml x2) preceded by Bupivacaine 0.5% (10ml, central). Patients and the research nurse were blinded to treatment arm. Narcotic usage was measured as mg of morphine equivalent. Follow up included a 7-point Likert pain scale, Global rating scale of change (GRSC), and narcotic use at 3, 7, 30, 60, 90 and 120 days, survival, and the incidence of adverse events (ASGE criteria).

Results:
36 patients were enrolled from November 2021 to December 2022; of whom 30 achieved complete 120 day follow up. The results are summarized in Table 1. Patients were comparable at baseline. There were no differences in intra-procedural variables. Post-procedure, the bupivacaine group showed significantly lower BP at discharge. The alcohol only group tended to have lower pain scores and higher reduction in pain and morphine use at T120 days. There were significantly more mild adverse events in the bupivacaine group.

Conclusions:
Preliminary results of this ongoing randomized trial suggest that adding bupivacaine to alcohol for EUS-CPN significantly increases mild adverse events and may reduce effectiveness in terms of pain relief and need for narcotics.