Introduction

The principal treatment option for treating chronic lymphoproliferative disorders (CLPD) is chemotherapy. The central concept in chemotherapy (CT) is adherence to the dose and drug administration regimens. It is impotent that infusion of CT agents in high doses is associated with an increased risk of chemotherapy-induced injury of the entire gastrointestinal tract (GIT).
The clinical manifestations of chemotherapy-induced mucositis are diarrhea. The presence of chemotherapy-induced injury mucositis can be assessed by the level of N-acetylneuraminic acid (NANA) and citrulline in the blood. The primary mechanism of the cytotoxic influence of CT agents is strongly associated with oxidative stress.

Aims & Methods

The aim is to investigate the effect of S-ademetionine on plasma NANA and citrulline levels in patients with CLPD during chemotherapy-induced injury The aim is to investigate the effect of S-ademetionine on plasma NANA and citrulline levels in patients with CLPD during chemotherapy-induced injury GIT.
Materials and methods: 24 patients with CLPD were examined (15 (75%) patients with B-cell chronic lymphocytic leukemia and 10 (25%) patients with Small B-cell non-Hodgkin lymphoma, 7 (28 %) females and 18 (72 %) males, ages 30-76. The inclusion criteria were the progression of B-CLL, Small B-NHL, and diarrheal syndrome on the background of CT. The examinations were conducted twice: before CT and after 3 courses of CT. Patients were analyzed the concentration of NANA in the blood, and the concentration of the citrulline in the plasma.
All patients received CT: BR (bendamustine, rituximab), FCR (fludarabine, cyclophosphamide, rituximab), R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone). Depending on the inclusion of S-ademetionine as an adjuvant treatment, patients were divided into groups: І (n=13) – patients with CLPD, who received only CT. ІІ (n=14) – patients with CLPD, who received S-ademetionine at a dose of 1000 mg/day intravenously for 10 days, then 500 mg twice a day for 20 days. ІІІ (n=20) – the control group of 20 practically healthy individuals (9 (45 %) females and 11 (55 %) males, ages 22-26).

Results

Patients in both groups with CLPD had pre-existed mucosal injury characterized by 1.25 (p=0.0025) and 1.26 times (р=0.006) higher blood NANA concentration than the control group. The conduction of CT was associated with injury enterocytes, which was characterized by 1,66 times (p=0,0002) lower plasma citrulline level in patients of group I compared to the initial examination. The infusion of S-ademetionine attenuated intestinal dysfunction associated with 1,23 times (p=0,0005) higher blood citrulline level after the CT compared to group I.

Conclusion

The infusion of S-ademetionine as adjuvant treatment in patients with CLPD provided effective prophylaxis of GIT injury that was associated with higher blood citrulline levels after the conduction of CT.

Disclosure

No

Introduction

ERCP is a commonly used endoscopic procedure for diagnosing and treating disorders of pancreaticobiliary system. NSAIDs have been proven to minimize the risk of post-ERCP pancreatitis, which occurs in approximately 8% of average-risk procedures (1,2). This study aimed to analyze the occurrence of post-ERCP pancreatitis in patients in whom ERCP was performed for the first time, before and after the use of NSAIDs in routine clinical practice.

Aims & Methods

Between January 2012 and December 2014 and between January 2019 and December 2021, 621 and 664 patients, respectively, were consecutively evaluated. In all those patients therapeutic ERCP procedure with biliary sphyncteroctomy has been done for the first time and the post-procedure complications were consecutively evaluated. NSAIDs were administered in a form of rectal suppositories at least an hour before the procedure. Post-ERCP pancreatitis was defined as an appearance of pain with elevated amylase concentrations at least 3x above the upper limit of normal for more than 24 hours after the procedure. Chi-Square test and Mann-Whitney U tests were used to compare discrete and continuous variables where p<0.05 was considered statistically significant.

Results

A total of 1285 ERCP-naïve patients were analyzed. Patients were split into two groups, one receiving and the other not receiving NSAID prophylaxis (667 vs 618 patients, respectively). Patients who received NSAID prophylaxis showed a significantly lower incidence of post-ERCP pancreatitis (2.9% vs. 7.8%, p<0.05) and transient hyperamylasemia (9.3% vs. 28.2%, p<0.05), as well (Table 1).

Table 1. NSAID non-NSAID

Conclusion

Real-life experience from a single tertiary center demonstrated that including NSAID prophylaxis into standard clinical practice resulted in a considerable reduction in post-ERCP pancreatitis and hyperamylasemia.

References

1. Buxbaum JL, Freeman M, Amateau SK, Chalhoub JM, Coelho-Prabhu N, Desai M, Elhanafi SE, Forbes N, Fujii-Lau LL, Kohli DR, Kwon RS, Machicado JD, Marya NB, Pawa S, Ruan WH, Sheth SG, Thiruvengadam NR, Thosani NC, Qumseya BJ; (ASGE Standards of Practice Committee Chair). American Society for Gastrointestinal Endoscopy guideline on post-ERCP pancreatitis prevention strategies: summary and recommendations. Gastrointest Endosc. 2023 Feb;97(2):153-162. doi: 10.1016/j.gie.2022.10.005. Epub 2022 Dec 12. PMID: 36517310.
2. Pekgöz M. Post-endoscopic retrograde cholangiopancreatography pancreatitis: A systematic review for prevention and treatment. World J Gastroenterol 2019;25:4019-4042.

Disclosure

no conflict of interest

Introduction

Agonists and antagonists of G protein-coupled receptors (GPCRs) are widely used medications that serve in the therapy of constipation, diarrhea, and pain. However, little is known about how the effect of those drugs is modulated by Regulator of G Protein Signaling (RGS) proteins which promote timely silencing of the GPCR responses. RGS proteins have been documented to regulate the magnitude and duration of signals initiated by several types of GPCRs occurring in the GI tract, including opioid and cannabinoid receptors. Serving as a central control point in GPCR signaling cascades, RGS proteins hold great promises as targets for the drug development however their expression profile and function in the gut constitute a major gap in the knowledge.

Aims & Methods

The major emphasis of this study is on elucidating the expression and function of RGS proteins in physiology and pathophysiology of the GI tract. We hypothesize that identification of RGS proteins and GPCR signaling pathways that they control will reveal novel molecular targets combating GI disorders. METHODS: We used total RNA sequencing to evaluate the expression profile of RGS proteins in the mouse ileum and colon. Then we confirmed the expression of the most abundant transcripts with the qPCR and measured the expression of proteins with Western blot. Then in the in vivo conditions we used an RGS6 knockout (RGS-/-) mouse model to evaluate the effect of this protein on intestinal motility, pain and inflammation in naïve mice as well in the presence of the cannabinoid agonist WIN 55,212-2.

Results

RNA sequencing showed similar profile of expression of RGS proteins in the ileum and colon. qPCR analyses showed that Rgs2, 5 and 6 are the most abundant transcripts in the colon. At the level of protein we observed that RGS6 exhibits the highest expression in the ileum colon as well as intestinal intraepithelial lymphocytes. Moreover we observed a significant increase in RGS6 expression in the mouse colon samples during intestinal inflammation. In vivo experiments showed that RGS6-/- animals exhibit increased intestinal motility in physiological conditions and resistance to stress-induced diarrhea. Moreover RGS6-/- animals exhibit anti-nociceptive phenotype and are more susceptible to the analgesic effect of WIN 55,212-2. We did not observe the impact of RGS6 on the severity of colitis in the DSS-induced model.

Conclusion

Here we present RGS6 protein as a novel candidate for drug targeting in the GI tract. Our study suggests that loss and perhaps also pharmacological blockade of RGS6 might be used as standalone or an adjunct treatment to increase the potency of cannabinoids in the gut. The project is ongoing and further experiments are pending.

Introduction

Despite the usefulness of white light endoscopy (WLE) and nonmagnified narrow band imaging (NBI) for screening superficial esophageal squamous cell carcinoma (SESCC) and precancerous lesions, these lesions may be missed due to their subtle features and interpretation variations among endoscopists.

Aims & Methods

Our team has developed an artificial intelligence (AI) system to detect SESCC and precancerous lesions using WLE and nonmagnified NBI. This study aims to evaluate the impact of this AI system on clinical diagnosis.
A prospective tandem study was conducted to evaluate the auxiliary diagnostic performance of the AI system in a real clinical setting. Consecutive patients undergoing sedated upper gastrointestinal endoscopy at 12 hospitals in China were recruited. Patients were randomly assigned to either the AI-assisted first group or the routine first group at a 1:1 ratio. The same endoscopist at each center performed tandem upper gastrointestinal endoscopy for each eligible patient on the same day. In the AI-assisted group, the endoscopist performed the first examination with the assistance of the AI system and the second examination without it. In the routine first group, the order of examinations was reversed. The primary outcome was the miss rate of SESCC and precancerous lesions. The secondary outcome including the detection rate of SESCC and precancerous lesions.

Results

Between October 2021 and June 2022, a total of 5,856 eligible patients were included and randomly assigned to the AI-assisted first group and 5,850 were assigned to the routine first group. The per-lesion miss rate was significantly lower in the AI-assisted first group than in the routine first group (1.7% vs 6.7%; Risk ratio (RR)=0.25; p=0.08). The detection rate in the AI-assisted first group was significantly higher than that in the routine first group (1.8% vs 1.3%; RR=1.38; p=0.03).

Conclusion

The proposed AI system can reduce the miss rate and improve the detection rate of SESCC and precancerous lesions during upper gastrointestinal endoscopy under WLE and non-magnified NBI.