Introduction

Zastaprazan is a novel potassium-competitive acid blocker (P-CAB) with fast onset and prolonged duration. This study aims to assess the efficacy and safety of zastaprazan compared to esomeprazole in patient with erosive oesophagitis.

Aims & Methods

A phase 3, multicentre, randomised, double-blind, active-controlled clinical study was conducted with 300 subjects with confirmed erosive oesophagitis (Los Angeles classification grades A to D). Subjects were randomised to receive zastaprazan 20 mg or esomeprazole 40 mg once daily up to 8 weeks. The primary endpoint was the cumulative proportion of subject with healed erosive oesophagitis confirmed by endoscopy up to week 8. The secondary endpoints included the healing rate at week 4, symptom response and quality of life. Safety profiles and serum gastrin levels were also assessed. [ClinicalTrials.gov: NCT04282954]

Results

The cumulative healing rate at week 8 were 97.9% for zastaprazan and 94.9% for esomeprazole. The difference was 2.98% (95% CI, -1.36 to 7.32, FAS). The cumulative healing rate at week 4 was 95.1% for zastaprazan and 87.7% for esomeprazole with a statistically significant difference of 7.44% (95% CI, 0.92 to 13.97, FAS) (p <0.05). The incidence of adverse events was comparable between groups, and zastaprazan was well-tolerated. Serum gastrin levels significantly increased during the treatment and declined after the treatment.

Conclusion

An 8-week therapy of zastaprazan 20 mg is non-inferior to esomeprazole 40 mg in subjects with erosive oesophagitis. The healing rate at week 4 appears to be higher for zastaprazan than esomeprazole at week 4, which further investigation is warranted. These findings suggest that zastaprazan would be a promising alternative to proton pump inhibitors for the treatment of erosive oesophagitis.

Disclosure

Funding for this clinical study was provided by Onconic Therapeutics.

Introduction

Endoscopic intermuscular dissection has been described to successfully treat rectal pathology when deeper dissection levels are needed for en bloc resection and a clear vertical dissection margin, through dissection of the inner circular muscle from the outer longitudinal muscle of the rectum (1-4). The conventional technique is performed with carbon dioxide insufflation. However, since our description of the saline-immersion/irrigation technique (SITE), this has proven to overcome the disadvantages that occur with the use of CO₂ or de-ionised water (5-6). These include improved endoscopic visualization by reduction of any gas/fluid interface or fat micelles, intrinsic magnification, natural-traction through buoyancy, maintenance of a thick, fluid-soaked submucosa, enhanced patient comfort during operator-delivered conscious sedation, through less distension of the bowel and superior electrical conductivity, obviating the need for higher diathermy

Aims & Methods

A 43-year-old female underwent TAMIS for excision of a bulky sessile rectal lesion. The procedure had to be interrupted due to an intra-procedural complication. At follow-up colonoscopy 3 months after, a residual 50mm sessile (Paris 0-Is, LST-G-MN, JNET 2A) rectal lesion was identified in an area of severe fibrosis. Multidisciplinary team discussion favored endoscopic resection with endoscopic submucosal/intermuscular dissection (ESD/EID)

Results

SITE-ESD was selected as the preferred therapeutic approach. In the area of severe scarring, the distinction between planes was extremely challenging and submucosal space was not detectable, therefore, EID was warranted with some parts of the muscle removed full-thickness. Traction with clip-band was applied to gain access underneath the lesion and facilitate dissection. Resection time was 270 minutes. The deepest parts of the resection site was closed with clip-line method and protein-matrix gel was applied on the surface of the defect. The patient was safely discharged home 48 hours after the procedure, without any significant adverse events. Histopathological examination showed a tubulo-villous adenoma with low-grade dysplasia and focal high-grade, confirming R0 resection
6 months follow-up colonoscopy showed granulation tissue in the centre of the scar, with 2 residuals clips attached. This tissue was excised for histopathological analysis, without evidence of lesion recurrence, dysplasia or malignancy. More than 10 sessile serrated lesions were removed through the colon, suggesting an underlying serrated polyposis syndrome

Conclusion

SITE-EID is a feasible technique for rectal pathology when deeper excisions margins are required to achieve R0 resection, in severe fibrosis or deep submucosal invasion, avoiding the need for invasive surgery. SITE facilitates this technically demanding procedure through enhanced visualization, buoyancy and patient comfort. Further study is merited

References

1. Pimentel-Nunes P, Dinis-Ribeiro M, Ponchon T, Repici A, Vieth M, De Ceglie A, et al. Endoscopic submucosal dissection: European Society of Gastrointestinal Endoscopy (ESGE) Guideline. Endoscopy 2015;47:829–54.
2. Moons LMG, Bastiaansen BAJ, Richir MC et al. Endoscopic intermuscular dissection for deep submucosal invasive cancer in the rectum: A new endoscopic approach. Endoscopy 2022; 54: 993–8.
3. Nabi Z, Samanta J, Dhar J et al. Device-assisted endoscopic full-thickness resection in colorectum: Systematic review and meta-analysis. Dig Endosc 2024; 36: 116–28.
4. Guillaumot MA, Barret M, Jacques J et al. Endoscopic full-thickness resection of early colorectal neoplasms using an endoscopic submucosal dissection knife: A retrospective multicenter study. Endosc Int Open 2020; 8: E611–16.
5. Despott EJ, Murino A. Saline-immersion therapeutic endoscopy (SITE): An evolution of underwater endoscopic lesion resection. Digestive and Liver Disease [Internet]. 1. Dezember 2017 [zitiert 25. August 2023];49(12):1376. Verfügbar unter: http://www.dldjournalonline.com/article/S1590865817310538/fulltext
6. Yamamoto H, Hayashi Y, Despott EJ. The pocket-creation method for endoscopic submucosal dissection combined with saline-immersion: another potential option to overcome challenges in colorectal endoscopic submucosal dissection. Gastrointest Endosc [Internet]. 1. August 2019 [zitiert 6. August 2023];90(2):288–9. Verfügbar unter: https://pubmed.ncbi.nlm.nih.gov/31327340/

Disclosure

The authors declare the following conflict of interest
EMB: No disclosures
GK: No disclosures
AR: No disclosures
AM: Personal payments/honoraria/fees: Olympus Medical, Laborie, Boston Scientific, Fujifilm Healthcare Europe
EJD: Educational grants in support of conference organization, and honoraria, from Fujifilm Healthcare Europe, Pentax, and Olympus Medical, and honoraria from Ambu and Fujifilm Healthcare Europe