Proximal intestinal mucosal ablation for the treatment of type 2 diabetes. These are our disclosures. Gastric bypass surgery is a highly effective metabolic treatment for patients with type 2 diabetes. Excluding nutrients from the proximal intestines causes an almost immediate and weight independent improvement in blood glucose. Due to the endoscopic accessibility of the duodenum, ablation of the abnormal and hypertrophied duodenal mucosa has been proposed as a metabolic treatment for type 2 diabetes. Duodenal mucosal ablation aims to selectively destroy up to 15cm of duodenal mucosa to emulate the metabolic effects of gastric bypass. However, this is much shorter than the average biliopancreatic limb length of 50-60cm formed during bypass surgery. Ablation length has been limited by the accessibility to safely deliver ablation beyond the duodenum of current technology, which could be overcome with a through-the-scope system. We propose a novel procedure that extends the length of mucosal ablation within the proximal intestines up to 75cm. The extended length, more akin to bypass surgery, is hypothesized to induce a better and more durable glycemic response. So we present the novel PEMA procedure, or proximal intestinal mucosal ablation. This is achieved by vapor ablation using radiofrequency energy that converts saline into heated water vapor. It's delivered to the intestines with a through-the-scope catheter, which at the end has a mesh tip that directs and releases steam to the mucosa to induce thermal injury. So we present a 56-year-old female with inadequately controlled type 2 diabetes despite maximum dose metformin. Their baseline glycated haemoglobin was 10%, their body mass index was 34.2kgsm2, and they had no other major comorbidities. After a 4-week run-in period to ensure stable glycemic control on current therapy, they proceeded to the PEMA procedure. So an initial screening enteroscopy is completed with an adult colonoscope to ensure no contraindications to the PEMA procedure. Initially, the proximal ablation zone is marked with an endoscopic clip that's placed contralateral to the ampulla. The catheter is then inserted and we see deployment of the mesh tip. Steam is then released from ports within a 2.5cm treatment zone with foot pedal activation at a dose of 250J, and at the end of ablation, the mesh is retracted back into the sheath. So here the catheter is inserted, the mesh is deployed, and the first vapour ablation can be delivered immediately distal to the clip. The catheter is positioned, the mucosa suctioned down onto the mesh, and then steam ablation delivered with foot pedal activation. At the end of the ablation, the mesh is retracted and the area of ablation can be assessed. Sequential ablations are then given during the first run of the procedure, ensuring minimal overlap and going in a proximal to distal direction. Here we can see the catheter was repositioned immediately distal to the previous ablation, and then a steam ablation was delivered, and the catheter is now being retracted to assess the zone. The endoscope is then pushed forward, catheter inserted again, mesh deployed, and the same process can take place to deliver excellent circumferential steam ablation. During the procedure, buscopam may be given at several intervals to prevent peristalsis to allow better mucosal contact with the mesh tip. Again, the mesh is deployed, positioned, mucosa suctioned down and steam ablation is delivered. Here on withdrawal we can see the excellent circumferential mucosal ablation appearance. At the end of the first run of ablations, the ablated segment is inspected for any complications or any missed areas. Any water that may have been produced during the procedure is suctioned. Once that's complete, the second run of vapor ablations are then delivered, going the same proximal to distal direction to create a series of double application of steam ablation. Here we can see the endoscope being advanced within the duodenum and proximal jejunum to apply the second overlapping ablation. Here again, the mesh tip is being deployed, positioned, mucosa suctioned and then steam ablation delivered. So, once we've done the complete second application of steam ablation, the entire ablated segment is then inspected. Here we can see fantastic circumferential mucosal ablation. The endoscope is slowly withdrawn, checking for the ablation surface, checking for any complications. And then if we see any missed areas, additional ablation may be given. So here, an additional vapour ablation is planned to be given because there's a small missed area. So the endoscope can be inserted and withdrawn throughout the ablated segment to really assess at the end of the procedure. Once this assessment has been completed, the procedure is complete. So the patient was discharged the following day on a modified diet for 14 days without complication. The maximum visual analogue score for pain was 3 on day 1 and there were no serious adverse events or hypoglycemia. Follow-up endoscopy at 28 days was unremarkable with normal biopsies from the ablated segment. At one month follow-up, HbA1c reduced significantly by 1.8% going from 10% to 8.2% despite only a modest reduction in BMI. So in conclusion, the PEMA procedure is safe, feasible and early efficacy is excellent for the treatment of type 2 diabetes. The extended length of ablation within the PEMA procedure has the potential for both greater reduction and more durable improvement in HbA1c without compromising safety or technical feasibility. We are continuing to investigate the safety and longer term efficacy of the PEMA procedure in an extension to our first in-human study.

Proximal Intestinal Mucosal Ablation

type 2 diabetes

radiofrequency energy

glycemic improvements

duodenal mucosa