Introduction

Japanese gastrointestinal stromal tumor (GIST) guidelines recommend that gastric submucosal tumors (SMT) < 2 cm should be followed up once or twice a year if asymptomatic and without malignant findings (ulceration, irregular border, and/or tumor growth), and SMT with malignant findings or a pathological diagnosis of GIST are relative indications for surgery¹. However, this management policy for SMT < 2 cm has not been fully evaluated.

Aims & Methods

This study aimed to clarify the long-term outcomes of patients with endoscopically diagnosed gastric SMT < 2 cm managed according to the guidelines. Patients with endoscopically diagnosed gastric gastrointestinal mesenchymal tumors (eGIMT) < 2 cm, including GIST, leiomyomas, and schwannomas, at our institution between September 2002 and December 2020 were included in this study. eGIMT was defined as an SMT with the same color as the surrounding mucosa, negative cushion sign, and mobility by biopsy forceps and/or a hypoechoic mass arising from the fourth layer of the gastric wall on endoscopic ultrasonography (EUS). The success rates of histological diagnosis by biopsy and EUS-guided fine needle aspiration biopsy (EUS–FNAB), rate of eGIMT with tumor growth during the endoscopic follow-up period, predictive factors of tumor growth, disease-specific survival (DSS), and overall survival (OS) rate were retrospectively evaluated. Tumor growth was defined as an increase in tumor size of approximately ≥ 5 mm compared to the initial tumor size, as measured by endoscopy. Factors associated with tumor growth like age, sex, number of lesions, stomach location, atrophic gastritis, and initial tumor size were considered for predictive analysis.

Results

A total of 1,519 patients with 1,632 eGIMTs were enrolled in this study. The median age at the initial diagnosis of eGIMT was 66 years (range, 28–90 years), and 60% of the patients were males. The percentage of patients who underwent EUS was 16%. The tumor locations were upper in 71%, middle in 20%, and lower in 9%, with the median initial tumor size being 5 mm and 24% were ≥ 1 cm. The success rates of histological diagnosis using biopsy and EUS-FNAB for eGIMT were 12% and 87%, respectively. Among the 927 patients with 995 eGIMTs examined at least twice by endoscopy and followed up endoscopically for at least 1 year, tumor growth was observed in 3.8% (median endoscopic follow-up period, 5.3 years). Of these, 33 patients underwent surgery or endoscopic resection, and the final pathological diagnoses of eGIMT were 4 high-risk GISTs, 1 intermediate-risk GISTs, 15 low-risk GISTs, 9 very low-risk GISTs, and 3 schwannomas. In univariate analysis, the only predictive factor of tumor growth was initial tumor size (< 1 cm: 1% vs. ≥ 1 cm: 14%, p < 0.0001). The 5–year DSS and 5–year OS rates of all patients with an eGIMT < 2 cm were 100% and 86%, respectively (median follow-up period, 5.2 years).

Conclusion

The long-term outcomes of patients with an eGIMT < 2 cm managed according to the current guidelines were favorable. Tumor growth in patients with an eGIMT < 1 cm is rare and may allow for extended follow-up intervals.

References

1. Nishida T, Hirota S, Yanagisawa A, et al. Clinical practice guidelines for gastrointestinal stromal tumor (GIST) in Japan: English version. Int J Clin Oncol 2008;13:416-30.

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

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.

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.

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.