Introduction

Distinguishing gastrointestinal stromal tumors (GISTs) with high malignant risk is essential for the management of small submucosal tumors (SMTs).

Aims & Methods

We aimed to develop a machine learning model based on endoscopic ultrasound (EUS) images to diagnose GISTs and non-GISTs as well as distinguish their potential malignancy. EUS images of 205 small gastric SMT (<2cm) patients were retrospectively included in the model development phase. An automatically optimized radiomics modeling system (AORMS) framework was developed to carry out the model learning based on the features extracted from the retrospective cohort. Three-fold cross-validation was used to train the machine learning model and produce the optimal model for differentiating between GIST and non-GIST as well as groups 1 and 4 GIST. Images of 178 patients from different centers were prospectively enrolled in the validation phase of the model. The diagnostic performance of the AORMS was evaluated in the development set and compared with the performance of endoscopists. Then, the performance of the AORMS was evaluated in the prospective validation set.

Results

The overall area under the curve (AUC), accuracy, sensitivity, and specificity of the AORMS were 0.762, 0.708, 0.819 and 0.649 for the diagnose of GIST, and 0.734, 0.872, 0.571 and 0.908 for the risk stratification of group 1 and 4 GIST. The accuracy of five experienced endoscopists ranged from 0.449 to 0.531 in diagnosing GIST, and from 0.702 to 0.809 in distinguishing group 1 and 4 GIST. The overall performance of AORMS is better than that of experienced endoscopists. In the prospective validation set, the AORMS also achieved 0.770 and 0.750 AUC for the diagnosis and risk stratification of small GISTs (<2cm).

Table 1. Diagnostic performance of the AORMS.

Conclusion

AORMS showed good and stable performance in diagnosis and risk stratification of GISTs, which may help endoscopists provide more accurate diagnosis for small gastric SMTs (<2cm).

Introduction

Neuroendocrine neoplasms are a group of tumors originating from neuroendocrine cells and peptidergic neurons. Rectal neuroendocrine tumors (NETs) are the second most common location for gastrointestinal NETs, albeit representing only 2% of all rectal neoplasms. Most of these are nonfunctional and asymptomatic although pain, blood loss and perianal discomfort can occur in larger lesions.
Endoscopically, rectal NETs typically appear as small and well-delimited submucosal lesions, with a yellowish color. The risk of lymph node metastasis is related to the tumor size, therefore, the current guidelines consider endoscopic resection as an option for rectal NETs smaller than 2 centimeters. The classical options for lesion removal include endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD). However, EMR has a higher risk of incomplete resection, whereas ESD is more invasive and has an increased risk of complications (namely bleeding and perforation).
In this setting, underwater endoscopic mucosal resection (UEMR) appeared as an alternative that facilitates the complete removal of a lesion through the filling of the intestinal cavity with water. Previous Eastern studies suggest a higher complete resection rate with this endoscopic technique when compared to conventional EMR.

Aims & Methods

The present study aimed to evaluate the outcomes of patients submitted to UEMR of rectal NETs in a reference center.

Results

A total of 5 patients underwent UEMR for rectal NETs (Table 1). 3 patients had a tumor from the proximal rectum and 2 patients from the distal rectum. The tumor size ranged between 4 and 8 millimeters.
After marking the lesion borders, the entire rectal cavity was filled with saline and UEMR was performed. The lesion scar was closed with endoscopic clips in all cases. In a single case, delayed rectal bleeding was observed 3 days after procedure, solved with application of an additional endoscopic clip, without the need of inpatient management. No other complications were reported.
A R0 resection was observed in 80% of the cases. In a single case a positive basolateral margin was observed. However, after performance of a second UEMR in the scar (where no endoscopic evidence of residual lesion was found), there was absence of lesion in the histopathological sample. All the tumors had a G1 grade in the WHO 2019 Classification for Neuroendocrine Tumors, with a Ki-67 index ranging between 1 and 3%.
In all the cases there was absence of residual lesion or recurrence in the follow up endoscopy.

Conclusion

This case series showcases UEMR as an effective alternative to conventional EMR, achieving high satisfactory complete resection rates, while having a low rate of procedure related complications. Therefore, UEMR should be contemplated when considering an endoscopic removal for rectal neuroendocrine neoplasms.

References

1. Rinke, Anja et al. “European Neuroendocrine Tumor Society (ENETS) 2023 guidance paper for colorectal neuroendocrine tumours.” Journal of neuroendocrinology vol. 35,6 (2023)
2. Srirajaskanthan, Rajaventhan et al. “Optimising Outcomes and Surveillance Strategies of Rectal Neuroendocrine Neoplasms.” Cancers vol. 15,10 2766. 15 May. 2023
3. Shi, Haitao et al. “Underwater endoscopic mucosal resection for rectal neuroendocrine tumors (with videos): a single center retrospective study.” BMC gastroenterology vol. 22,1 276. 2 Jun. 2022
4. Okada, Masahiro et al. “Underwater Endoscopic Mucosal Resection of Small Rectal Neuroendocrine Tumors.” Frontiers in medicine vol. 9 835013. 19 Apr. 2022

Introduction

Ulcerative colitis (UC) treatment requires a patient-centric efficacy endpoint to assess treatment benefits, enabling a shift towards a personalized approach. Comprehensive disease control (CDC) is an individual multi-component endpoint based on findings from a patient and expert Delphi consensus on remission assessment in UC. CDC was defined as IBDQ remission, partial Mayo Clinic Score (pMCS) remission, biomarker (faecal calprotectin [FCP]) remission and endoscopic improvement.

Aims & Methods

We evaluated different definitions of CDC, and the contribution of different CDC components to the net treatment benefit (NTB) of filgotinib 200 mg (FIL200), an oral, once-daily, Janus kinase 1 inhibitor approved for UC treatment following the SELECTION trial (NCT02914522). CDC was assessed at week 58 (W58) of SELECTION in adult patients with active UC treated with FIL200 or placebo (PBO). The CDC definitions evaluated were: 4-component CDC (CDC4) with FCP <150 µg/g, CDC4-150; CDC4 with FCP <250 µg/g, CDC4-250; 5-component CDC (with histological remission [CDC5]) with FCP <150 µg/g, CDC5-150; and CDC5 with FCP<250 µg/g, CDC5-250. The proportion of patients achieving each combination of components was evaluated. NTB of FIL200 was assessed for each endpoint using generalized pairwise comparisons and is reported here for CDC4-150 (and excluding different components).

Results

At W58, 21.6%, 26.6%, 19.1% and 22.6% of FIL200-treated patients achieved CDC4-150, CDC4-250, CDC5-150 and CDC5-250, respectively. Among patients who did not achieve CDC4-150, 0.5% of patients did not achieve this composite endpoint because they did not achieve pMCS remission; whereas 5.0%, 10.1% and 6.0% did not do so because they did not achieve IBDQ remission, biomarker remission or endoscopic improvement, respectively. Positive overall NTB of FIL200 versus PBO was demonstrated with all CDC definitions, including those with histological remission (CDC5). For CDC4-150 at W58, excluding pMCS remission did not substantially change the NTB (Δ −0.33; Table) versus excluding IBDQ or biomarker remission, or endoscopic improvement (Δ 3.87, 6.93 and 3.20, respectively). Similar NTB results were seen for all CDC definitions, with or without histological remission.

Conclusion

CDC is a stringent, patient-level, multi-component endpoint achieved by ~1/5 of FIL200-treated patients at W58. While CDC4-150 could be the optimal operational definition, the addition of histological remission resulted in similar stringency, potentially allowing for the use of different CDC definitions based on context or resources. Additional NTB of FIL200 was identified in patients when IBDQ or biomarker remission or endoscopic improvement were excluded. Overall, CDC appears to be a suitable endpoint to assess individual comprehensive benefit in patients with UC. Prospective validation is needed.

Table. NTB with exclusion of different components of the CDC4-150 endpoint.

Disclosure

We thank Katrien Van Beneden for her contribution to conceptualization, investigation and data interpretation.
The SELECTION trial was sponsored by Gilead Sciences, Inc. (Foster City, CA, USA). Galapagos NV (Mechelen, Belgium) was a collaborator for the SELECTION trial and funded this analysis.
Medical writing support for the development of this abstract was provided by Hannah Stephens, PhD, of PharmaGenesis London, London, UK, and was funded by Alfasigma S.p.A.
VV and AO are employees of Alfasigma S.p.A at the time of abstract submission
SS has received personal fees from AbbVie, Amgen, Arena Pharmaceuticals, Biogen, Bristol Myers Squibb, Celgene, Celltrion, Dr Falk Pharma, Eli Lilly, Ferring Pharmaceuticals, Fresenius Kabi, Galapagos/Gilead Sciences, I-Mab, Janssen Pharmaceuticals, MSD, Mylan, Pfizer, Protagonist, Provention Bio, Sandoz/Hexal, Takeda, Theravance Biopharma and UCB.
BGF has received grants and personal fees from AbbVie, Amgen, AstraZeneca, Bristol Myers Squibb, Janssen Biotech/Centocor, Johnson & Johnson/Janssen, Pfizer, Receptos and Takeda; and personal fees from Ablynx, ActoGeniX, Akebia Therapeutics, Inc., Allergan, Atlantic Pharmaceuticals, Avaxia Biologics, Inc., Avir Pharma, Baxter Healthcare Corporation, Biogen Idec, BiomX Israel, Boehringer Ingelheim, Boston Pharmaceuticals, Calypso Biotech, Celgene, Elan/Biogen, Eli Lilly, enGene, Ferring Pharmaceuticals, Galapagos, Genentech/Roche, gIcare Pharma, Gilead Sciences, Given Imaging, Gossamer Bio, GSK, Inception IBD, Inc., Ironwood Pharmaceuticals, Japan Tobacco Company, Kyowa Hakko Kirin Co. Ltd, Lexicon Pharmaceuticals, Lycera, Mesoblast, Millennium Pharmaceuticals, MSD, Nestlé, Nextbiotix, Novartis, Novo Nordisk, Par’Immune, Progenity, Prometheus, Protagonist, Qu Biologics, Q32 Bio (formerly AdMIRx, Inc.), Salix Pharmaceuticals, Shire, Sienna Biopharmaceuticals, Sigmoid Pharma, Synergy Pharma, Teva Pharmaceuticals, TiGenix, Tillotts Pharma, UCB, Vertex Pharmaceuticals, VHsquared, Vivelix Pharmaceuticals, Wyeth, Zealand Pharma and Zyngenia.
SV receives financial support for research from AbbVie, Galapagos, Johnson & Johnson, Pfizer and Takeda; speaker and/or consultancy fees from AbbVie, Abivax, AbolerIS Pharma, AgomAb Therapeutics, Alimentiv, Arena Pharmaceuticals, AstraZeneca, Bior Therapeutics (formerly Progenity), Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Cytoki Pharma, Dr Falk Pharma, Eli Lilly, Ferring Pharmaceuticals, Galapagos, Genentech-Roche, Gilead Sciences, GSK, Hospira, IMIDomics, Janssen Pharmaceuticals, Johnson & Johnson, Materia Prima, Mestag Therapeutics, MiroBio, Morphic, MRM Health, MSD, Mundipharma, Pfizer, ProDigest, Prometheus, Robarts Clinical Trials, Surrozen, Takeda, Theravance Biopharma, Tillotts Pharma AG, VectivBio, Ventyx Biosciences and Zealand Pharma.
SD reports personal fees from AbbVie, Allergan, Amgen, AstraZeneca, Athos Therapeutics, Biogen, Boehringer Ingelheim, Celgene, Celltrion, Eli Lilly, Enthera, Ferring Pharmaceuticals, Gilead Sciences, Hospira, Inotrem, Janssen Pharmaceuticals, Johnson & Johnson, MSD, Mundipharma, Mylan, Pfizer, Roche, Sandoz, Sublimity Therapeutics, Takeda, TiGenix, UCB and Vifor Pharma.
MF is an employee and shareholder of Galapagos NV.
VV and AO are former employees and shareholders of Galapagos NV, and employees of Alfasigma. S.p.A.
LP-B has received consulting fees from Abivax, AbbVie, Alimentiv, Alma Bio Therapeutics, Amgen, Applied Molecular Transport, Arena Pharmaceuticals, Biogen, Bristol Myers Squibb, Celltrion, CONNECT Biopharma, Cytoki Pharma, Eli Lilly, Enthera, Ferring Pharmaceuticals, Fresenius Kabi, Galapagos, Genentech, Gilead Sciences, Gossamer Bio, GSK, HAC Pharma, IAG Image Analysis, Index Pharmaceuticals, Inotrem, Janssen Pharmaceuticals, Medac, Mopac, Morphic, MSD, Norgine, Novartis, OM Pharma, ONO Pharma, OSE Immunotherapeutics, Pandion Therapeutics, Par’Immune, Pfizer, Prometheus, Protagonist, Roche, Roivant, Samsung, Sandoz, Sanofi, Takeda, Theravance Biopharma, Thermo Fisher Scientific, TiGenix, Tillotts Pharma, VectivBio, Ventyx, Viatris, Vifor Pharma and Ysopia; grants from Celltrion, Fresenius Kabi and Takeda; and speaking fees from AbbVie, Amgen, Arena Pharmaceuticals, Biogen, Celltrion, Eli Lilly, Ferring Pharmaceutics, Galapagos, Genentech, Gilead Sciences, Janssen Pharmaceuticals, Medac, MSD, Pfizer, Sandoz, Takeda, Tillotts Pharma, Viatris and Vifor Pharma.

Introduction

Patients with type 2 diabetes are prone to the development of dysbiosis, which can manifest as intestinal bacterial overgrowth (SIBO). This may explain the pathomechanism of abdominal symptoms that sometimes affect this group of patients. Disturbances in the composition and quantity of intestinal microbiota translate to impaired production of short-chain fatty acids (SCFA) in the intestinal mucosa. To increase the concentration of butyrate in the lumen of the intestine, oral microencapsulated sodium butyrate supplementation can be proposed. Given the limited research conducted on the topic of the effects of sodium butyrate supplementation in alleviating abdominal symptoms in patients with type 2 diabetes, it became the topic of our interest.

Aims & Methods

The aim of the study was to evaluate the effectiveness of oral sodium butyrate supplementation in the population of patients with type 2 diabetes in alleviating abdominal symptoms and to estimate the incidence of small intestinal bacterial overgrowth in this group. In addition, the impact of the intervention on the carbohydrate metabolism was assessed.A prospective, single-centre, randomized, placebo-controlled study was conducted between October 2022 and April 2023.
52 patients with type 2 diabetes and gastrointestinal symptoms were randomly assigned to one of 2 groups - a group receiving microencapsulated sodium butyrate (Intesta Max) at a dose of 1.5 g/day and a group receiving placebo. As 8 patients (15.3%) were lost to follow-up, for the preliminary analysis 44 patients were included. The study lasted for 6 weeks. Before and after the intervention the presence of abdominal pain, diarrhoea, constipation and flatulence was assessed, laboratory tests and hydrogen breath tests were performed, the HOMA index and body mass index were calculated.

Results

At baseline SIBO was diagnosed in 73.1% of patients in the experimental group and 58.8% of patients in the control group. After 6 weeks of the intervention there was a significant drop in SIBO occurrence in sodium butyrate group – 22.2% (p=0.001). The incidence of SIBO in the control group did not change – 64.7% (p=0.21).All patients included in the study declared abdominal pain before the intervention. After 6 weeks the pain was reported by 42.3% of the patients receiving the sodium butyrate vs. 88.4% of the patients receiving placebo (p=0.002). After the intervention there was a significant difference between the groups regarding diarrhea – 18.5% and 58.8% (p=0.006) in sodium butyrate and placebo groups respectively. A decrease in the incidence of bloating in the sodium butyrate group was observed - 100% before vs. 29,6% after the intervention (p<0.00001). The study also showed a decrease in BMI level, the HOMA index and glycated hemoglobin level after consumption of the sodium butyrate vs. placebo for 6 weeks. These results need confirmation in a larger group.

Conclusion

To our knowledge this is the first study reporting the effectiveness of oral butyric sodium supplementation in relieving abdominal symptoms (abdominal pain, diarrhea, flatulence) in patients with type 2 diabetes. Furthermore, an improvement in carbohydrate metabolism parameters was noted and body weight decrease was observed after the intervention.

Disclosure

Sodium butyrate (Intesta Max) we received from the company that produces it.

Clinical Case Summary

A 62 y/o male complaining from epigastric pain, constipation, vomiting and eructation for two months and CT abd revealed irresectable pancreatic head mass 4.5x4.5 cm encasing PV and SMV with duodenal invasion. Ryle decompression was done before EGD, duodenal obstruction was noted and biopsy showed duodenitis (stasis induced). EUS-FNB confirmed well differentiated AC. Duodenal stenting was successfully performed with improving symptoms.
After one week patient complained from weakness and abnormal gait, examination showed normal vital signs, bilateral lower limb edema and patient was lethargic. Three days after, the patient became confused (GCS 12), so he was admitted to ICU.
CT brain was unremarkable. Lab investigations showed the following:
Na 130, K 4.1, Ca 7.8, Phos 2.8, Mg 2.6, Alb 2.9
Refeeding injury was suspected and TPN was started by the ICU team. No improvement of the consciousness was achieved and patient caught chest infection, developed sepsis and died.
Discussion: Refeeding syndrome is a serious complication that can be easily missed [1] in upper GI malignant obstructions with prolonged decreased oral intake along with the malignancy cachexia status. These obstructions may need surgery or stenting to regain patency and without cautious monitoring of the nutrients repletion rate either enteral or parenteral this will lead to fluid and electrolyte disturbance (Fluid balance abnormalities, Abnormal glucose metabolism, Vitamin deficiency, e.g., vitamin B1 (thiamine), Hypophosphatemia, Hypomagnesaemia and/or Hypokalemia) [2] with symptoms ranging from vague up to life threatening conditions like disturbed conscious level and heart failure. Our patient had high risk of developing refeeding syndrome due to caloric deprivation secondary to duodenal obstruction with development of the symptoms after stenting and restarting oral intake.
Conclusion: Nutritionist counseling after GI stenting of upper GI malignant obstructions is needed to avoid refeeding syndrome.

References

[1] Reber, E., Friedli, N., Vasiloglou, M.F., Schuetz, P. and Stanga, Z., 2019. Management of refeeding syndrome in medical inpatients. Journal of clinical medicine, 8(12), p.2202.
[2] Crook, M.A., Hally, V. and Panteli, J.V., 2001. The importance of the refeeding syndrome. Nutrition, 17(7-8), pp.632-637.

Introduction

Atrophic gastritis(AG) is mainly caused by Helicobacter pylori(Hp)infection or autoimmunity. Hp-related AG affects both corpus and antral mucosa resulting in multifocal AG(MF-AG), whereas AG driven by autoimmunity is corpus-restricted(CR-AG).
Corpus mucosa gastric atrophy carries an increased risk of gastric dysplasia(GD) and cancer(GC);the neoplastic risk in CR-AG is considered lower, but still debated. GD-GC lesions in AG may arise in the antrum, incisura angularis or, less frequently,the corpus.Data on characteristics and potential differences of GD-GC lesions between MF-AG and CR-AG are lacking.

Aims & Methods

This study aimed to assess clinical,endoscopic,and histological characteristics of GD-GC in MF-AG and CR-AG pts.
A multicenter,cross-sectional study was conducted across 14 Italian GI centers. Data on GD-GC in patients with MF-AG or CR-AG(2001-2023) were retrospectively collected based on clinical,endoscopic, and histological charts: site,dimension,endoscopic,and histologic features of GD-GC, perilesional gastric antral and corpus mucosa(updated Sydney system),and patients’ clinical data (age,sex,outcome after GD-GC diagnosis,Hp infection, parietal cell antibodies(PCA), family history for GC). Inclusion criteria were:patients with MF-AG or CR-AG and GD or GC diagnosis,aged>18 years, availability of endoscopic and histological description of GD-GC and perilesional gastric mucosa, completeness of clinical data.Data were stratified for MF-AG/CR-AG and the GD-GC, perilesional mucosa, and clinical characteristics were compared.

Results

A total of 84 pts[(F46[54.8%];age 70(33-90yrs)] were included. MF-AG and CR-AG were observed in 45(53.6%) and 39(46.4%) pts,respectively. High-grade(HG)-GD,low-grade(LG)-GD,and non-cardia GC were diagnosed in 6(7.1%),31(36.9%), and 47(56.0%)pts.
Age, GC family history,smoking habits, and PCA positivity were similar between MF-AG and CR-AG.Women(69.2% vs 42.2%,p=0.01) and pernicious anemia(29% vs 9.1%,p=0.04) were more frequent in CR-AG than in MF-AG.
The proportion of GD and GC in MF-AG and CR-AG pts was similar:HG-GD was present in 4(8.9%) vs 2(5.1%),LG-GD in 17(37.8%) vs 14(35.9%),GC in 24(53.5%) vs 23(59.0%)pts(p>0.05).
Compared to MF-AG,in CR-AG pts GD-GC were more frequently polypoid lesions (51.6% vs 27.3%,p=0.048) and more frequent in the corpus (55.3% vs 28.6%,p=0.02), but also occurred in the antrum(34.2%) and incisura(10.5%).The intestinal-type GC was the most prevalent and was more frequent in MF-AG than in CR-AG (87%vs60.9%,p>0.046), while diffuse GC was 2 times more frequent in CR-AG than in MF-AG, albeit not reaching statistical significance (26.1% vs 13%, p=0.27).
Concerning GC differentiation grade and staging, no significant differences were observed between MF-AG and CR-AG.Endoscopic treatment of GD-GC was similar in both groups. CR-AG patients underwent surgery more frequently than MF-AG(48.6% vs 23.1%,p=0.0207), but outcome was similar with 90.7% MF-AG and 92.1% CR-AG pts being alive.
Histopathological features of corpus mucosa (acute-chronic inflammation, severity of atrophy,pseudopyloric and intestinal metaplasia) were similar between MF-AG and CR-AG(p>0.05). The histological evidence of Hp in the antrum and corpus was low in both groups (2.3% vs 2.9%,p=0.87).

Conclusion

Non-cardia GC and GD may occur in both,MF-AG and CR-AG, displaying differences in topography and endoscopic presentation, but similarities in perilesional gastric corpus mucosa, differentiation, staging and outcome.
Endo-histological surveillance should be considered in pts with gastric corpus atrophy, irrespective of its etiology and extension.

References

Lahner E, et al. Dig Liver Dis. 2019 Dec;51(12):1621-1632.
Lenti MV, et al. Nat Rev Dis Primers. 2020 Jul 9;6(1):56.
Rugge M, et al. Gut. 2023 Jan;72(1):30-38.