Introduction

Endoscopic sleeve gastroplasty (ESG) is a minimally invasive restrictive bariatric procedure associated with significant weight loss, obesity-related comorbidities improvement, and a favorable safety profile. The suturing devices, available today, are often tricky and operator-dependent. A novel automated endoluminal-sutured gastroplasty system (EndoZip™, Nitinotes Ltd. based in Israel), has been developed to simplify and standardize ESG. The device is positioned in the gastric body under endoscopic vision and is connected to an external vacuum pump that captures the gastric wall segments into the distal end of the device. The activation of a motor system makes a custom-designed needle pass through the tissue and allows stitching, tightening, clipping, and cutting of suture wire. The suturing actions are done automatically in approximately 2 minutes, by just pressing on the operation button.

Aims & Methods

This multicenter, prospective, single-arm study aimed to assess the safety and efficacy of the ESG using EndoZip™ for the treatment of obesity. Patients with a BMI of 30 to 40 kg/m² unable to lose weight with non-invasive approaches and deemed suitable for bariatric endoscopic according to the multidisciplinary team were enrolled in 3 centers (Spain, Italy and Israel). The efficacy of the EndoZip™ system was assessed. %TBWL, and % of patients with %TBWL ≥5% were evaluated via ANCOVA model. Safety data and physician's satisfaction with device use, were evaluated via descriptive statistics.

Results

Forty-five patients underwent robotic endoscopy-assisted gastric volume reduction. The mean +SD age was 44 +8 years, and BMI was 34.6 +2.9 kg/m², respectively. The majority of the patients were female (89%). the average procedure time was 30 minutes. We used an average of 3.9 sutures; At 12 months, the mean +SD %TBWL was 13.5 + 10.4%. We observed >5% TBWL in 79.4% of the patients (Table 1). All endoscopists found the device easy to use. Serious adverse events occurred in 2 patients (bleeding and gastric perforation). The bleeding was stopped with endoscopic clipping, and the gastric perforation required surgical closure. No mortality occurred.

	1 month	2 months	4 months	6 months	12 months
Adj. Mean %TBWL (Lower 95% CL)	7.4% (6.6%)	10.3% (8.9%)	13.3% (11.5%)	14.5% (11.7%)	13.5% (10.4%)
%TBWL ≥5% (Lower 95% CL)	78.6% (63.2%)	92.7% (80.1%)	92.3% (79.1%)	85.0% (70.2%)	79.4% (62.1%)
Per Protocol Analysis

Conclusion

EndoZip™ system is an operator-friendly and reproducible procedure with promising efficacy and safety results.

Disclosure

Ivo Boskoski is a consultant for Apollo Endosurgery, Cook Medical, Boston Scientific, and Nitinotes.

Introduction

Female sex and increasing age are risk factors for constipation. Studies have found colon transit times to be longer in women. When estrogens decrease, constipation appears or worsens among perimenopausal women. After recommendation of lifestyle changes, second-line treatment are pharmaceutical solutions such as laxatives. However, most laxative agents show limited efficacy for chronic use, especially in people with comorbid conditions or concomitant medication inducing constipation (antihypertensives, calcium supplements to prevent osteoporosis, ...) in addition to potential adverse effects.
Intermittent colonic exoperistalsis (ICE) administered with the MOWOOT medical device, is a non-invasive, non-pharmacological treatment for chronic constipation. It has been developed to facilitate natural bowel movements and reduce the side effects of laxatives, enemas, or other invasive approaches. ICE has been proven safe and effective in constipation from both neurogenic or idiopathic aetiology in a multicentric clinical trial. Here, its use among women with functional chronic constipation was evaluated.

Aims & Methods

Adult women with chronic functional constipation were recruited in 4 hospitals in Germany. The treatment consisted of using the ICE device for 15 to 30min daily, at home. Patient outcomes were self-reported through anonymous, structured feedbacks collected at baseline (F1) and after some time under ICE treatment (F2).

Results

Data resulted from n=17 women(6 aged 18-39 yr, and 11 aged 40-80 yr). Twelve of them had a previous diagnosis of slow colonic transit. The mean time of ICE treatment at F2-feedback collection was 6,60(5,21) months (min 0,5; max 16). No one reported any serious adverse event. Three patients described occasional low self-remitting adverse events which did not affect the treatment compliance.

		Baseline (F1)	Treatment (F2)	Change (F2-F1)	P
Suppositories	Yes(F1)/Same(F2)	12	1	-11	0,0002 a
	No(F1)/No or Less(F2)	5	16
Oral Laxatives	Yes(F1)/Same(F2)	15	6	-9	0,0039 a
	No(F1)/No or Less(F2)	2	11
Number Bowel Movements / week		2,65(1,86)	5,75(2,97)	3,10	<0,0001 b
Time (min) / Bowel Movement		110,4(149,7)	52,4(73,0)	-57,94	0,0314 b
Average Bristol scale (1-7)		2,65(1,54)	3,75(1,73)	1,25	0,0099 c

Results are shown as N or mean(SD). a: Chi² & Fisher's exact test; b: Student's t-Test for paired values; c: Wilcoxon matched-pairs test.

Of the 12 women using suppositories at F1, 11 (92%) had reduced its use at F2, including 9 (75%) that stopped completely. Of the 15 women using oral laxatives, 9 (60%) had reduced its use, including 4 (27%) that fully stopped. Overall, 3 women (25%) had stopped both suppositories and oral laxatives, and only 1 (8%) maintained the same dose of both. In total, 80% (12/15) of women stopped or reduced some form of laxative (Table).
In addition to laxative reduction, bowel movements increased on average by more than 3 per week, fecal consistency ameliorated (Bristol scale), and time spent in each bowel movement was reduced by nearly 1h (Table).

Conclusion

The use of ICE treatment by chronically constipated adult women significantly improved their bowel function. Importantly, this amelioration was accompanied by a notable reduction in laxatives, with a high percentage of women stopping the use of suppositories.
This in-use structured feedback in the out-patient sector points to the clinical benefit of ICE treatment. Therefore, the ICE device has the potential to substitute more invasive and pharmacological approaches in bowel management strategies for women with functional constipation.

References

1. Bharucha AE, Wald A. Chronic Constipation. Mayo Clin Proc. 2019 Nov;94(11):2340-2357.
2. Houghton et al. Age, Gender, and Women’s Health and the Patient. Gastroenterology 2016;150:1332–1343
3. McClurg, D., L. Booth, and I. Herrero-Fresneda, Safety and Efficacy of Intermittent Colonic Exoperistalsis Device to Treat Chronic Constipation: A Prospective Multicentric Clinical Trial. Clin Transl Gastroenterol, 2020. 11(12): p. e00267
4. Special SCI units involved in recruitment: BDH Klinik, Greifswald, GE; Werner-Wicker-Klinic, Bad Wildungen, GE; Zentralkinik, Bad Berka, GE; Klinken Beelitz, Beelitz-Heilstätten, GE.

Disclosure

IHF works as CSO at MOWOOT, USMIMA S.L., the manufacturer of the ICE device. The author would like to thank Dr J. Bremer, Dr. P. Kossmehl, Dr. I. Kurze and Dr. H. Lienhard for their support in the above-mentioned SCI hospitals, and R. Müller for his support regarding the logistics of the study.

Introduction

Anti-TNF are the first biologic treatment option in inflammatory bowel diseases (IBD). Few data is available on the long term risk of relapse after anti-TNF withdrawal in paediatric-onset IBD, especially at the population level.

Aims & Methods

All paediatric-onset (<17 years) IBD diagnosed between 1988 and 2011 were included in a prospective population-based study and were retrospectively followed until 2013. Among patients treated with first-line anti-TNF, the cumulative probability of relapse after anti-TNF withdrawal was evaluated using a composite outcome (intestinal resection, and/or flare-related hospitalization, and/or IBD treatment initiation, and/or active disease). Factors associated with relapse were investigated with a Cox model.

Results

Among a total of 1,344 patients (Crohn’s disease (CD): n=1,007; Ulcerative colitis (UC): n=337), 562 were treated with anti-TNF. Anti-TNF was stopped in 73 patients (CD: n=66; UC: n=7) during remission defined by Harvey-Bradshaw score < 4 in CD and Mayo score ≤ 2 in UC. Among them, median time to anti-TNF initiation was 1.6 years (IQR, 0.7-4.0) and median duration of treatment was 1.0 year (0.3-1.7). The first line anti-TNF therapy was infliximab in 68 (93%) patients. At anti-TNF withdrawal, 47 (64%) patients received immunosuppressant. The cumulative probability of relapse after anti-TNF withdrawal at 1, 3 and 5 years was respectively 62%, 85% and 93%. Median delay of relapse was 9.5 months (7.5-12.0). The cumulative probability of flare-related hospitalization at 1, 3 and 5 years was respectively 7%, 7% and 8%. No patient required intestinal resection after a median follow-up of 8.7 (5.8-13.8) years. In multivariate analysis, median time to anti-TNF initiation >1 year was the only factor associated with the risk of relapse (HR 0.58, CI95% [0.35-0.97], p=0.036). Among relapsers, 46 (63%) were retreated with anti-TNF. Retreatment with anti-TNF was effective in 45 (98%) patients after a median delay of 3.9 months (3.5-10.0). Infusion reaction occurred in only 2 patients.

Conclusion

In a population-based cohort of paediatric-onset IBD, the risk of relapse after anti-TNF withdrawal was high, but was not associated with major complication. Retreatment with anti-TNF was effective and well tolerated.

Disclosure

Consultant fees from Sandoz and AbbVie

Introduction

Barrett’s esophagus (BE), the major precursor of esophageal adenocarcinoma (EAC), is a condition where the normal stratified squamous esophageal epithelium undergoes transdifferentiation into the specialized, intestinal-like epithelium. This reprogramming, also termed ‘paligenosis’, is predominantly caused by gastroesophageal reflux disease (GERD)¹. On the other hand, hydrogen sulfide (H₂S) next to carbon monixide (CO) is an important endogenous gaseous mediator. H₂S is biosynthesized by cystathionine β-synthase (CBS) and cystathionine γ-lyase (CTH). Both, H₂S and CO have been shown to maintain gastrointestinal (GI) integrity^2,3,4. However, the contribution of gaseous mediators signaling to esophageal transdifferentiation process is overlooked.

Aims & Methods

Thus, in this study we aimed to explore the role of H₂S bioavailability in mTOR-dependent paligenosis induced by chronic epithelial injury. Furthermore, we evaluated the relationship between GERD, the barrier function of cultured cells, and the pattern of selected components involved in the formation of the tight junctions (TJs) and responsible for epithelial barrier integrity.
We implemented an animal model of GERD, based on Male Wistar rats with esophagogastroduodenal anastomosis (EGDA) treated i.g. for 8 weeks with vehicle or with H₂S- releasing chemicals: GYY4137 (5.0 mg/kg)/NaHS (1.0 mg/kg) or CTH/CBS inhibitors: PAG (15 mg/kg)/AOAA (11 mg/kg). In parallel, we employed optimized in-vitro GERD model based on human-derived esophageal epithelial (EPC2) cells +/- CRISPR-Cas9-induced knockout of H₂S-producing enzymes that were treated with acidified bile mixture (BM) or with GYY4137/NaHS (100 µM). We evaluated activation of AKT/mTOR pathway by multiplex microbeads fluorescent assay and an expression of TJ-associated protein (ZO-1) and occludin by capillary immunoblotting. The barrier function of cultured cells was evaluated by measurement of transepithelial electrical resistance (TER).

Results

We observed that either chronic reflux in EGDA-rats and/or treatment of human esophageal cells with BM led to a slight or a significant activation of AKT/mTOR signaling pathway and its down-stream effector - p70S6K. Additionally, we observed that pharmacologically-derived H₂S reversed this effect, while inhibition of endogenous H₂S biosynthesis (pharmacological or induced by knockout of H₂S-producing enzymes) had either no effect or increased GERD-induced phosphorylation of AKT/mTOR pathway components. Moreover, we showed that ZO-1 is highly expressed in BM treated EPC2 cells and this was reflected by the increase in TER measurment. Level of occludin remained unchanged. We did not observe any changes in expression of ZO-1 and occludin after GYY4137 treatment; however, TER measurment decreased in comparison to BM treated cells. Selective knockout of H₂S-producing enzymes led to a decrease in ZO-1 protein content in comparison to wild-type cells.

Conclusion

We conclude that interventional enhancing or decreasing of H₂S bioavailability in esophageal epithelium respectively delay or accelerate the GERD-induced paligenosis process via regulation of the mTOR pathway. H₂S-prodrugs may provide a protective effect on the esophageal epithelium by substituting the phisiological defensive response of the tissue against GERD, which is reflected by an increase in the expression of ZO-1 and tightening of the cellular barrier.

References

1. Souza RF, Spechler SJ. Mechanisms and pathophysiology of Barrett oesophagus. Nat Rev Gastroenterol Hepatol 2022.
2. Fiorucci S, Distrutti E, Cirino G, Wallace JL. The emerging roles of hydrogen sulfide in the gastrointestinal tract and liver. Gastroenterology 2006.
3. Magierowska K, Korbut E, Wójcik-Grzybek D, Bakalarz D, Sliwowski Z, Cieszkowski J, Szetela M, Torregrossa R, Whiteman M, Magierowski M. Mitochondria-targeted hydrogen sulfide donors versus acute oxidative gastric mucosal injury. J Control Release 2022.
4. Magierowska K, Brzozowski T , Magierowski M. Emerging role of carbon monoxide in regulation of cellular pathways and in the maintenance of gastric mucosal integrity. Pharmacol Res 2018.

[Funding: National Science Centre, Poland (UMO-2016/23/D/NZ4/01913, UMO-2019/33/B/NZ4/00616) and Statutory Grant (N41/DBS/000874), Jagiellonian University Medical College].

Clinical Case Summary

Introduction: Henoch Schoenlein Purpura (HSP) is an IgA immune mediated vasculitis. It is usually preceded by upper respiratory tract infection. It is more common in males. It is more predominant in paediatric population. However, its incidence in adults is extremely rare with 3.4-14.3 cases / million. Only 10-20% of patients present with gastrointestinal symptoms.
Case presentation: A 39-year-old male presented with rash, abdominal pain, vomiting and watery diarrhoea. His rash was non-itchy non-painful purpuric petechial which covered both upper and lower limbs consistent with HSP. He had diffuse angiokeratoma type lesions on the dorsum of his feet, hands, lateral side of thighs and buttocks. He upper respiratory tract infection for 1 week. Vitals signs were unremarkable. Bloods showed high CRP, ESR, IgA and WBCs. Procalcitonin was negative. ASO showed high titers. The rest of his bloodwork was negative including autoimmune screen and ANCA. Urine analysis showed persistent haematuria with negative urine culture.
CT abdomen showed jejunal wall thickening and oedema with fat stranding and mesenteric nodes. MRI small bowel found abnormal oedematous loops of small bowel proximally within the left flank. keeping with acute small bowel inflammation. However, distribution was not classical for inflammatory bowel disease. Rheumatology team started him on steroids for suspected Henoch-Schoenlein Purpura. He improved subsequently.
Discussion: This patient presented with HSP related enteritis after he had a recent upper respiratory tract infection and HSP characteristic rash. He was treated successfully with steroids.
Conclusion: Clinicians should be aware that Henoch Schoenlein Purpura could be present in adults despite being more prevalent in children. Clinicians should suspect HSP in adults when a patient presents with classic rash, abdominal symptoms and raised inflammatory makers after a recent upper respiratory infection.

References

Nevrekar RP, Bhandare P, Khandeparkar A. Clinical Spectrum of Henoch Schonlein Purpura in Adults: A Hospital Based Study. J Assoc Physicians India. 2022;70(2):11-12.

Introduction

Endoscopic ultrasonography-guided gastroenterostomy (EUS-GE) is emerging as a new and minimally invasive endoscopic treatment method for gastric outlet obstruction (GOO). In EUS-GE, it is important that stents can be safely and reliably deployed and that there is no stent migration. As the optimal method, we have developed the EUS-guided balloon-occluded gastrojejunostomy bypass (EPASS) and have performed it as a clinical study.

Aims & Methods

We retrospectively evaluated the results of EPASS including long-term outcomes. The EPASS procedure was performed under conscious sedation. The endoscope was used to reach the site of obstruction. The stricture was cannulated with a 0.025-inch guidewire and the guidewire was used to negotiate beyond the site of obstruction under endoscopic and fluoroscopic guidance. The double balloon tube was then inserted on the guidewire beyond the duodenal–jejunal flexure using an overtube. The two balloons of the occluder were inflated with 30–40 mL normal saline and constrast. 200–300 mL of methyleneblue-stained saline was then injected to distend the occluded segment of duodenum. A linear echoendoscope was then inserted into the stomach. A site in the posterior wall of the body of the stomach was punctured directly by the delivery system of the lumen apposing metal stent. A 20 x 10 or 15 x 10 mm stent was used. The distal flange of the stent was deployed under EUS guidance, followed by deployment of the proximal flange under endoscopic or EUS guidance. Stent position was confirmed with the drainage of methylene-blue-stained saline, the endoscopic view of the proximal flange and also the fluoroscopic image. Thirty-six consecutive patients with symptomatic GOO who were not refractory to surgical gastrojejunostomy were enrolled in the study. The primary endpoint was technical success rate. Secondary endpoints included procedure time, GOO scoring system (GOOSS) scores at 7 days and 1 month after EPASS, clinical success rate (improvement in GOOSS scores at 7 days after EPASS), procedure-related adverse events (AEs) rate, overall survival (OS) after EPASS in the 23 patients with long-term follow-up, and stent patency rate.

Results

The mean age was 70.6 years (range 47-91), 16 (44%) were female, and the underlying diseases were 18 pancreatic cancer, 9 gastric cancer, 3 duodenal cancer, 4 gallbladder cancer, 1 breast cancer, and 1 chondrosarcoma. The technical success rate was 94.4% (34/36), mean procedure time was 26.9 minutes (range 14-40), mean time to double-balloon tube insertion was 9.8 minutes (range 6-28), mean pre-GOOSS score was 0.42, mean GOOSS score was 2.08 and 2.21 at 7 days and 1 month after EPASS, and the clinical success rate was 88.9% (32/36). The incidence of procedure-related AE was 16.7% (6/36), including 2 cases of fever, 2 cases of abdominal pain, and 2 cases of worsening ascites. The mean overall survival after EPASS was 183.8 days, all patients died of primary disease, and there were no events such as stent occlusion or stent deviation (stent patency was 100%).

Conclusion

EPASS is a safe and reliable EUS-GE method and may be a useful treatment for symptomatic malignant GOO.

References

(1) Tsuchiya T, et al. Tech Innov Gastrointest Endosc. 2020;22:27-32.
(2) Itoi T, et al. J Hepatobiliary Pancreat Sci. 2020;27:791-792.
(3) Itoi T, et al. Gut 2016;65:193-5

Disclosure

Lecture fee : Boston Scientific Japan, Olympus Japan