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.

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

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

Introduction

While patients with Sickle Cell Disease (SCD) often exhibit digestive manifestations, the underlying pathophysiology remains poorly understood. SCD could notably affect the intestinal mucosa through microvascular phenomena. Co-occurrence of SCD and Inflammatory Bowel Diseases (IBD) has been reported in a very limited number of cases.
Our aim was to explore the intersection between SCD and IBD, particularly focusing on the impact of SCD on the natural course of IBD and the safety profile of drugs in this high-risk population.

Aims & Methods

We conducted a multicenter retrospective case-control study involving all adult patients diagnosed with both IBD and concomitant SCD and followed in 3 tertiary university hospitals. Each IBD patient with SCD was matched with up to 4 IBD patients without SCD, based on disease phenotype (UC or CD), sex, date of birth (±3 years), length of disease follow-up (±2 years), and year of diagnosis (±3 years). The primary outcome was a complicated disease course, defined by a composite outcome including intestinal resection, perianal surgery, and/or the need for advanced therapy.

Results

Overall, 125 patients with IBD were studied, including 24 with concomitant SCD and 101 controls. Of the 24 SCD patients, 5 (20.8%) had Crohn's disease (CD), 17 (70.8%) had ulcerative colitis (UC) and 2 (8.3%) had indeterminate colitis. 23/24 (95 %) had colonic involvement. Of note, 8 of 24 (33.3%) SCD patients had concomitant primary sclerosing cholangitis (PSC) compared to 1% of patients in the control group (p<0.001). Survival without a complicated course of the disease was estimated at 58.7 % (IC95[49.6-69.5]) at 5 years and at 38.9% (IC95[29.9-50.4]) at 10 years, for non-SCD patients, and at 63.3% (IC95[45.7-87.6]) and 52.7% (IC95[34.9-79.6]) at 5 and 10 years, respectively, for patients with SCD and IBD (p=0.36, Log-rank test). The survival without the need of advanced therapy was estimated at 66.1% (IC95[57.3-76.2]) at 5 years for non-SCD patient, and at 78.2% (IC95[63-97.2]) in patients with SCD patients (p=0.45).
Regarding the safety profile, 26.3% (5/19) of patients with SCD and 13.5 % (14/104) of controls experienced adverse events with advanced therapies (p=0.17, Fisher’s exact test). There was one reported vaso-occlusive crisis associated with the use of thiopurines. No death occurred during follow-up.

Conclusion

While patients with SCD and IBD displayed a distinctive phenotype characterized by nearly constant colonic involvement and a high prevalence of associated PSC, the disease natural history of IBD did not differ from that of patients without SCD. Given the notable prevalence of PSC, systematic screening with cholangio-MRI should be considered. Furthermore, no significant safety signal regarding the use of immunomodulator or advanced therapy was raised.

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

Based on the Chicago classification, HREM diagnosis is classically based on metrics obtained with wet swallows carried out in the supine position. However, both patients and physicians often feel that this is not a physiological position to conduct the test as it may not translate to the real world experience. With the patient in the upright/sitting position, the test would more closely simulate real-life behaviour and may be safer for elderly patients at risk of aspiration.

Aims & Methods

In an Asian tertiary centre, a total of 104 patients had undergone high resolution esophageal manometry (HREM) with retrospective data analysis comparing both conventional supine position with the upright position. The latter is generally favoured by all patients as this represents the physiological posture during meals.

Results

Using 2-tailed paired sample T-test, comparison across all cases showed a consistently lower median Integrated Relaxation Pressure (IRP) [6.0 mmHg vs to 8.7 mmHg; p <0.01] and lower mean Distal Contractile Integral (DCI) [1463 mmHg/cm/sec vs 1864 mmHg/cm/sec; p =0.014] in the upright posture compared to supine position although the mean Distal Latency (DL) difference was not significant [6.21secs vs 6.27 secs; p =0.491]. During upright and supine position comparison respectively, subgroup analysis on subjects with normal HREM diagnosis showed even lower median IRP [4.9 mmHg vs 7.5 mmHg; p <0.01] and lower mean DCI results [1436 mmHg/cm/sec vs 1695 mmHg/cm/sec; p <0.01] with mean DL in this subgroup showing no significant statistical difference [6.29 secs vs 6.38secs; p=0.545]. The final HREM diagnosis in upright position is concordant with the conventional supine position up to 81.7% and showed an even higher concordance in terms of management similarity up to 98.1%. Only 2 cases (2/104) showed a significant discordance between supine and upright HREM diagnosis [normal HREM vs esophagogastric juntion –outflow obstruction(EGJ-OO) and hypercontractile esophagus vs normal HREM]. Minor diagnostic discordance [normal HREM vs ineffective esophageal motility (IEM)] was noted in 17/104 cases which had no major clinical impact on patients and may be overcome by adopting a lower cut-off for mean DCI for upright group.

Conclusion

In patients who are unable to perform HREM in supine position, adopting the upright position shows a high clinical concordance and may be considered a more physiological approach in the HREM protocol.

References

Riva CG, Siboni S, Ferrari D, Sozzi M, Capuzzo M, Asti E, Ogliari C, Bonavina L. Effect of Body Position on High-resolution Esophageal Manometry Variables and Final Manometric Diagnosis. J Neurogastroenterol Motil. 2020 Jul 30;26(3):335-343. doi: 10.5056/jnm20010. PMID: 32606256; PMCID: PMC7329148.

Introduction

Hypermobile Ehlers-Danlos syndrome (hEDS) is a hereditary non-inflammatory disorder of connective tissue laxity characterized by joint hyperextensibility in association with musculoskeletal symptoms. The prevalence of gastrointestinal (GI) symptoms, such as abdominal pain, nausea, and constipation is high in hEDS. Research on the relationship between EDS and GI symptoms has mostly been restricted to disorders of the gut-brain axis, whereas the relationship between hEDS and GI dysmotility remains to be clarified.

Aims & Methods

This study aimed to explore antro-duodenal manometry (ADM) patterns in patients with hEDS presenting with GI symptoms.

In a prospective open-label study, patients with hEDS and GI symptoms presumed to be the results of GI dysmotility underwent a 6-hour high resolution ADM. The manometry tracings were analyzed by two investigators (KS and JC) independently. Antral contraction frequency (contractions per minute) < 1.0 was considered as antral hypomotility. Pylorospasm was defined as isolated pyloric pressure waves within 60 minutes postprandial. The following neuropathic enteric patterns were scored: presence of retrograde peristalsis, bursts, clustered contractions, and absence of phase III contractions. Abnormal ADM was defined as having antral hypomotility and/ or pylorospasm and/ or neuropathic enteric patterns.

Results

Fifty patients (48 women, mean age 30.4 ± 11.1 yrs.) were included. At baseline, 74% of patients were dependent on enteral feeding and the mean BMI was 20.4 ± 4.4 kg/m².
Overall, ADM tracings with one or more abnormal patterns were identified in 53% of patients. Antral hypomotility and pylorospasm were detected in 29% and 15% of patients, respectively. Neuropathic enteric patterns were only seen in 17% of patients. In all cases, no more than one neuropathic pattern was identified. Among the observed neuropathic enteric patterns, 15% of patients showed retrograde peristalsis, 13% absence of phase III contractions, and 2% bursts. Clustered contractions were not identified in this cohort.

Conclusion

Hypermobile Ehlers-Danlos patients presenting with gastrointestinal symptoms showed low numbers of abnormal ADM patterns. In particular, enteric dysmotility was observed in only a small minority of cases. Antroduodenal dysmotility therefore does not appear to be a principle pathomechanism in the majority of hEDS cases studied. Further research is needed to understand the mechanisms that underlie GI symptom generation in this population.

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].