NITROUS OXIDE CRYOBALLOON ABLATION FOR ERADICATION OF NON-AMPULLARY SPORADIC AND FAMILIAL DUODENAL ADENOMAS: PRELIMINARY RESULTS OF A MULTICENTER CLINICAL TRIAL

Background:
Endoscopic ultrasound-guided gastroejejunostomy (EUS-GJ) has gained popularity in treating malignant gastric outlet obstruction (GOO). EUS-GJ has also been used to manage benign GOO with promising technical and clinical success. The long-term efficacy and course of EUS-GJ in benign GOO are important to understand given the longer treatment course entailed, compared to malignant GOO in which end of life may be eminent. The aim of this study was to determine efficacy and clinical course of EUS-GJ in benign GOO.
Methods:
This was a single center retrospective series. Consecutive patients who underwent EUS-GJ from January 2017 to May 2022 for treatment of benign GOO were included. The primary outcomes were technical and clinical success. The secondary outcomes included prior endoscopic treatment, adverse events, and follow-up (clinical and endoscopic).
Results:
A total of 16 patients (43.75% female; mean age 63.3 +/- 14.8 years) underwent EUS-GJ for benign GOO. The etiology of the patients’ respective GOO’s was intrinsic in 50% of patients (8/16) and extrinsic in 50% of patients (8/16). These included pancreatitis (n=5), NSAID induced stricture (n=4), peptic ulcer disease (n=2), and SMA syndrome (n=2) among others. Technical success was achieved in 100% (16/16) patients and clinical success was achieved in 93% (15/16) patients- one patient required stent exchange due to occlusion in the first month. Hot Axios^TM stent was used; 20 mm x 10 mm in 12 patients and 15 x 10 mm in 4 patients. Stents remained in place for an average of 329 days and 25% of patients (4/16) had their stents removed on follow-up. In total, 13 patients had follow-up endoscopy, 1 patient was lost to follow-up, and 2 patients died of other chronic illnesses. On endoscopic follow-up, the stent was patent in all patients with no evidence of tissue overgrowth. On follow-up, 10 patients had normal jejunal mucosa at an average of 5.9 months from EUS-GJ, 1 patient had jejunal erosions 6-months after the procedure, and 2 patients had ulcerations at an average of 6.5 months from the procedure.
Discussion:
This series adds to very limited literature on EUS-GJ for benign GOO, showing that it is both technically feasible and clinically beneficial. This study uniquely features follow-up at up to 1444 days from EUS-GJ. In the 4 of 16 patients whose stents were removed during the study, 75% of patients (3/4) had an extrinsic etiology, which was consistent with expectations given that extrinsic causes of GOO are more likely to resolve. No patients had stent damage or tissue overgrowth and most patients had normal jejunal mucosa on follow-up. Limitations of this study include the single center retrospective nature and the small sample size. A larger and prospective data set is needed to further describe the clinical course of EUS-GJ for benign GOO.

Endoscopic resection (ER) is the standard technique for the treatment of duodenal adenomas (DA). However, it can be technically challenging in flat lesions or lead to bleeding or perforation. A small retrospective study found that cryoballoon ablation (CBA) led to complete eradication (CE) of DA with no adverse events. AIM: To assess the safety and efficacy of nitrous oxide focal CBA in a prospective multicenter clinical trial (NCT03847636). METHODS: We enrolled patients with or without familial adenomatous polyposis (FAP) with benign non-ampullary DAs in the first or second portion with maximum diameter 1-5 cm, thickness <=4 mm (Paris 2a, 2b,1s) involving < 50% circumference and < 3 duodenal folds, no prior ablation or surgery. Prior EMR >6 weeks from CBA allowed. We excluded Paris 1p, 0-2c, 0-3 or malignant DAs. Using a cryogen dose of 8-12 seconds, we treated DA (up to 5 per procedure) at baseline and every 3 months until CE, maximum of 5 treatments in 1 year. Follow-up continued to minimum of 1 year. Primary endpoints: clinical response (>=50% eradication of treated DA using endoscopy and/or pathology), and change in Spigelman class (FAP only). Secondary endpoints: percent eradication, safety, technical success, procedure time. A 3-member expert panel blindly reviewed FAP images and videos and independently scored post-CBA response (+1 clinical improvement, 0 no improvement, -1 increase in DA size and number). RESULTS: To date, 28 patients enrolled, 19 (68%) completed treatment for 48 DAs, in a median of 2 procedures, within 4 min/DA (Tables 1a,1b). 6(21%) had prior EMR. Technical success was 86% (minor device malfunction or difficulty in positioning in 4 FAP patients). There were no serious adverse events; 4 patients had mild immediate transient post-procedure discomfort not requiring treatment. In 19 evaluable patients, we noted clinical response in 95%, with 90% complete, 5% partial (>=50% size reduction), and 5% minimal/no eradication (<50% size reduction) (Figure 1a). A median of 4 CBA procedures (IQR1-5) were needed to achieve CE. Median time for CBA per session was 4 minutes (IQR 2.2-7.8). The Paris classification of 48 of eligible treated polyps was 1s (13%), 0-2a (69%),0-2b (12%) or mixed (6%),with median diameter of 20 mm (IQR 15-30) (Table 1b).To date, in 38 of 48 polyps that completed treatment, we noted 26(74%) complete and 7(20%) partial eradication, with median decrease in DA size of 17 mm (IQR10-20) (Table1b). In all treated polyps, a clinical response was noted in 95% (Figures 1b, 2a-d). In FAP patients, blinded review showed improvement in polyp size and number in 4/4 and downgraded Spigelman class in 2/4 (Stage 3 to 2, Stage 3 to1). CONCLUSION: CBA is a safe, efficient, and effective therapy for DAs. Our preliminary results suggest it is a potential alternative therapy for select non-polypoid or thin sessile non-ampullary DA.