Clinical Case Summary

Introduction: Hemolymphangioma is a rare benign tumor characterized by malformation of both venous and lymphatic histological components. Hemolymphangioma occurs mainly in the head, neck and axilla, as well as in the spleen, pancreas, liver, spine and other areas, but rarely in the gastrointestinal tract.^1-4
Case report: We report the case of a 41-year-old man who manifested severe iron deficiency anemia. The patient complained for progressively worsening weakness and dizziness since months. He reported no signs of gastrointestinal bleeding or recent medication. During the physical examination, no pathological findings were found and the digital rectal examination was negative for the presence of blood. Laboratory testing revealed severe iron deficiency anemia (Hct: 23.7 %, Hb: 6.8 g/dl, WBCs: 6.00 K/μl, PLTs: 275.00 K/μl, MCV: 65.7 fl, MCH: 18.80 pg, MCHC: 28.70 g/dl). Subsequently, the patient underwent gastroduodenoscopy showing mild gastritis (histology: mild chronic inactive gastritis without H. pylori microorganisms) and ileocolonoscopy with normal findings. Afterwards, an endoscopy capsule was used to examine the small intestine and revealed a bleeding formation in the proximal part of the jejunum on the 29th minute of recording (Figure). Then, an attempt to find the bleeding mass was made by endoscopy of the upper digestive tract with a small colonoscope, but without success. Finally, the patient underwent surgery (with an intraoperative endoscopic examination) finding the known formation at 80 cm. from the ligament of Treitz. The surgical specimen was histologically examined with evidence supportive of small bowel hemolymphangioma. Abdominal CT scan revealed no other pathological findings.
Conclusions: In conclusion, we report a rare case of a small bowel hemolymphangioma, as the cause of severe iron deficiency anemia in a young patient, where endoscopic capsule of the small intestine plays a key role in the diagnostic approach of such cases.

References

1. Yang SX, Zhou YH, Zhang J, Miao L, Zhong JW, Wang WX, Xu CL, Cai ZZ, Lu GR. Haemorrhagic ileal haemolymphangioma: a case report and review of the literature. J Int Med Res. 2021 Feb;49(2):300060520986677.
2. Wu TL, Hsu HT, Yen HH. Jejunum lymphangioma: a rare case of obscure gastrointestinal bleeding with successful endoscopic therapy. Endoscopy. 2021 Aug;53(8):E307-E308.
3. Huang MY, Chang HM, Gao HW, Huang TY. Small Intestinal Lymphangioma With Lymphangioectasia Causing Obscure Gastrointestinal Bleeding. Am J Gastroenterol. 2017 Mar;112(3):413.
4. Iwaya Y, Streutker CJ, Coneys JG, Marcon N. Hemangiolymphangioma of the small bowel: A rare cause of chronic anemia. Dig Liver Dis. 2018 Nov;50(11):1248.

Introduction

Recent years have seen a significant increase in randomized controlled trials (RCT) published on the efficacy of probiotics on irritable bowel syndrome (IBS), which several reviews have tried to comprehensively review. Two recent trials, Yang et al. 2024¹ and Chen et al. 2023² report the safety and efficacy of probiotics for IBS, which seems to reflect prevailing favorable view of this therapeutic option by most reviews conducted. Yet, despite efforts in this field, major organizations have not changed their stance in this and make no assertive recommendation for probiotics in afflicted patients^3,4. While further investigations are required, two challenges are faced: (1) repeated reviews have been undertaken in this field, resulting in a "multiplicity problem", (2) traditional meta-analytic techniques may also fail to provide a conclusive answer on the sufficiency of evidence, particularly when the data are sparse, and the risk of type I and type II errors is significant. This indicates a need for.

Aims & Methods

This study aims to evaluate the efficacy of probiotics in alleviating symptoms of IBS and improve quality of life through a timely implemented trial sequential analysis (TSA) and rigorously evaluate the evidence for recommendations on future studies. Medline, Embase, Web of Science, and Cochrane were screened for randomized controlled trials (RCTs) comparing probiotics to placebo in adult patients with IBS. Primary outcomes included IBS Symptom Severity Score (IBS-SSS) and IBS Quality of Life (IBS-QOL) scores comparing probiotics and placebo groups. Traditional pairwise meta-analysis conducted in restricted maximum likelihood was conducted, with subsequent TSA . Study quality was graded according to risk-of-bias 2 (ROB-2) and certainty of evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE).

Results

42 studies were included. Overall, probiotics demonstrated non-significant improvements in IBS-SSS (MD: -27.64; 95% CI: -56.90 to 1.63; p=0.06) and IBS-QOL (MD: 1.33; 95% CI: -3.65 to 6.30; p=0.59). TSA was conducted on IBS-SSS demonstrated current evidence has not reached the required information size. The representative cumulative Z-curve demonstrated neither futility, benefit nor detrimental effect, indicating the need for further trials. Assessment with ROB-2 indicates high quality amongst most trials included in this study. GRADE evaluation of the evidence demonstrated low certainty of existing evidence.

Table 1: GRADE Evaluation

No. of studies	Study design	Risk of bias	Inconsistency	Indirectness	Imprecision	Other considerations	Probiotics	Placebo	Relative (95% CI)	Absolute (95% CI)	Certainty
Probiotics effectively reduces a patient's IBS-SSS score
24	randomised trials	not seriousa	very seriousb	not serious	very seriousc	publication bias strongly suspectedd	2237	1599	-	MD 27.64 lower (56.9 lower to 1.63 higher)	⨁◯◯◯ Very lowa,b,c,d
Probiotics effectively reduces a patient's IBS-QOL score
24	randomised trials	not seriousa	very seriousb	not serious	not seriouse	publication bias strongly suspectedd	2292	1712	-	MD 1.33 higher (3.65 lower to 6.3 higher)	⨁◯◯◯ Very lowa,b,d,e

CI: confidence interval; MD: mean difference

Two contributing factors to the low certainty of current evidence include: (1) Inconsistency of existing trials – there exists high level of heterogeneity as detected by statistical analysis through I² and Cochran Q amongst studies; (2) Suspected publication bias through inspection of a funnel plot, though Egger’s regression did not demonstrate statistical significance.

Conclusion

Existing evidence is insufficient to make conclusive recommendations regarding the role probiotics should play in the management of IBS in symptoms and QOL. Given the persistent heterogeneity and potential publication bias, future research should focus on standardizing probiotic interventions and clarifying their clinical utility to truly advance the field.

References

1. Yang R, Jiang J, Ouyang J, Zhao Y, Xi B. Efficacy and safety of probiotics in irritable bowel syndrome: a systematic review and meta-analysis. Clinical Nutrition ESPEN. 2024;
2. Chen M, Yuan L, Xie C-R, et al. Probiotics for the management of irritable bowel syndrome: a systematic review and three-level meta-analysis. International Journal of Surgery. 2023;109(11):3631-3647.
3. Su GL, Ko CW, Bercik P, et al. AGA Clinical Practice Guidelines on the Role of Probiotics in the Management of Gastrointestinal Disorders. Gastroenterology. 2020;159(2):697-705. doi:10.1053/j.gastro.2020.05.059
4. McKenzie Y, Thompson J, Gulia P, Lomer M. British Dietetic Association systematic review of systematic reviews and evidence‐based practice guidelines for the use of probiotics in the management of irritable bowel syndrome in adults (2016 update). Journal of Human Nutrition and Dietetics. 2016;29(5):576-592.
5. Lacy BE, Pimentel M, Brenner DM, et al. ACG clinical guideline: management of irritable bowel syndrome. Official journal of the American College of Gastroenterology| ACG. 2021;116(1):17-44.

Disclosure

All authors of the manuscript do not have a conflict of interest to declare.

Introduction

Many irritable bowel syndrome (IBS) patients report gastrointestinal (GI) symptoms due to various foods, resulting in food avoidance. However, a detailed description of trigger foods and related GI symptoms and avoidance behaviour is lacking. Therefore, we evaluated the extent and nature of food intolerance and avoidance in IBS patients, and its relation to GI symptoms and psychological comorbidities.

Aims & Methods

Food intolerance and avoidance behaviour were evaluated in 124 IBS patients and 113 healthy controls (HC) using a questionnaire with 257 food products of 13 food groups. Per product, participants were asked if they experience symptoms (i.e. nausea, constipation, diarrhoea, bloating, abdominal pain) after consumption, and if they consumed this product despite these symptoms. Furthermore, IBS symptom severity and psychological factors were assessed.

Results

IBS patients reported a higher number of food products with perceived intolerance than HC (median of 18.0 (25^th-75^th percentile 10.0-33.5) vs 1.0 (0.0-8.0), p<0.001). A wide variety of trigger foods was reported, with gas-producing foods and fatty/cream-based dairy products most frequently reported by both groups. Predominant symptoms were abdominal pain and bloating. The number of avoided foods was higher in IBS (15.0 (8.0-27.0) vs 1.0 (0.0-7.0), p<0.001). Food avoidance was not significantly related to symptom type, but was associated with an IBS diagnosis, female sex, and higher screening scores for somatisation and Avoidant/Restrictive Food Intake Disorder.

Conclusion

Self-reported food intolerance and avoidance is higher in IBS than HC, with a wide variety of trigger foods. Food avoidance was significantly related to psychological factors, but not to symptom type. This warrants individual dietary guidance, as well as attention for psychological factors.

Disclosure

D Keszthelyi: DK reports receiving research funding from ZonMw, MLDS, UEG, Rome Foundation, Horizon Europe, Horizon 2020, Grunenthal, Allergan and speaker’s fee from Dr Falk (paid to host institute).
DMAE Jonkers: DMAEJ reports receiving a public–private partnership grant of TKI Well on Wheat? and TKI grants from Agri & Food and Health Holland, the Carbokinetics programme as part of the Netherlands Organisation for Scientific Research–Carbohydrate Competence Center partnership, Organic A2BV/Mothersfinest, and Horizon 2020.

Introduction

ESD of the colorectal lesions involving the appendiceal orifice (AO) is technically challenging because of the thin wall and narrow working space. On the other hand, even if the lesions are small and benign, it is difficult to perform EMR because of the narrow snaring space. We previously reported strip biopsy (SB) resection of the AO lesion. The SB technique is as follows (1) Insert a 2-channel scope and check the lesion. (2) Insert a snare and grasping forceps into each channel, and hold the grasping forceps in the snare. (3) Grasp the appendiceal end of the lesion with the grasping forceps, open the snare, grasp the lesion, and resect it. This method makes it possible to snare the lesion after confirming the distal border of the AO. In the present study, we evaluated the feasibility of SB for AO lesions.

Aims & Methods

This was a retrospective study in which SB for AO lesions was performed on 10 patients at our hospital. Inclusion criteria for the study cohort were (1) the lesion less than 15 mm, and (2) visible lesion margin on the appendicular side. Polyps suspected to be cancerous were excluded.

Results

Male to female ratio was 8:2, median age (range) was 76 years (44-89). The median tumor size was 10 mm (10-15). The pathological findings were 8 cases of SSL and 2 cases of low-grade tubular adenoma. All lesions were resected en bloc, with a median treatment time of 10 minutes (range (5-10)). No complications were observed. Pathology results were negative for 8 cases and unknown for 2 cases. All lesions were resected endoscopically with no residuals.

Conclusion

SB technique for AO lesions is safe and it appeared that this could be one option for endoscopic treatment of AO lesions.^​

Introduction

The DOMINO diet app (diet) provides superior symptom relief to a spasmolytic agent (otilonium bromide, OB) in primary care Irritable Bowel Syndrome (IBS)¹. While the DOMINO diet aimed to provide a practical approach to lower intake of FODMAPs (fermentable oligo-, di-, monosaccharides and polyols), genetic polymorphisms in the eosinophil trafficking chemokine receptor CCR3 were associated with response to the diet². A correlation between fecal eosinophil-derived neurotoxin (F-EDN) and colonic mucosal eosinophil degranulation was previously reported in IBS³.

Aims & Methods

To assess a role for eosinophil-driven mucosal inflammation as a target for IBS therapy, we assessed changes in F-EDN levels in primary care patients treated with the DOMINO diet and OB, and their correlation with symptoms and inflammatory markers. In the DOMINO study, primary care physician-diagnosed IBS patients (70% fulfilling Rome IV, Rome+) were randomized to diet or OB. Analysis of gene polymorphisms, blood and stool samples were collected from 356 patients (86 IBS-C, 116 IBS-D, and 154 IBS-M) before and after treatment with diet and OB (respectively n=147 and 163). We compared and correlated F-EDN levels, demographic parameters, IBS symptom severity scoring (IBS-SSS), laboratory blood tests as well as biomarkers of inflammation in stool (secretory Ig/sIgA, Beta-defensin2, calprotectin). Statistical analysis was conducted using non-parametric tests; data were presented as median with interquartile range.

Results

Baseline F-EDN correlated negatively with presence of CCR3 polymorphism (r=-0.13, p=0.02), positively with sIgA (r=0.27, p<0.0001), but showed no significant associations with IBS-SSS scores or other stool parameters. Furthermore, a positive correlation was observed between F-EDN and glucose (r=0.16, p=0.004), insulin (r=0.14, p=0.01) and triglyceride (r=0.12, p=0.03) plasma levels and body weight (r=0.16/p=0.002). F-EDN decreased significantly in responders to the diet (≥50-point improvement on IBS-SSS) (n=104, 0.44μg/g[0.16;0.88] vs. 0.32μg/g[0.15;0.72], p=0.03), but not to medication (n=97, 0.48μg/g[0.16;1.01] vs. 0.44μg/g[0.19;0.87], p=0.57). In diet responders, baseline F-EDN levels correlated positively with calprotectin and sIgA (respectively r=0.24, p=0.01 and r=0.37, p<0.001). The significant decrease in F-EDN after diet was more pronounced in the subset of patients fulfilling Rome IV criteria (n=86, 0.47μg/g[0.17;0.91] vs. 0.34μg/g[0.16;0.75], p=0.02). Baseline F-EDN levels in this cohort correlated with the improvement in IBS-SSS (r=0.21, p=0.04).

Conclusion

In primary care IBS, response to the DOMINO diet, but not to OB, is associated with the presence and decrease of eosinophil-driven intestinal immune activation. Further research will focus on the ability of the DOMINO diet, besides its FODMAP-lowering properties, to improve atypical food allergic reactions involved in IBS pathophysiology.

References

1. Carbone, Van den Houte et al. Gut. 2022
2. Balsiger et al. Gut. 2023
3. Casado-Bedmar et al. Journal of Leukocyte Biology. 2022

Introduction

The protocol of the clinical trial OLGA (Operative Link for Gastritis Assessment) proposed in 2005 (M.Rugge & R. Genta, 2005) has become widely used in clinical practice as the method of unified assessment of the progression of atrophic gastritis and the risk of developing stomach cancer.
The protocol involves obtaining 5 fragments of the gastric mucosa: 2 fragments from the antrum, 2 fragments from the oxyntic part and 1 fragment from the incisura angularis. It was believed that the mucosa in this region, being in fact a transition zone between the location of the pyloric and oxyntic glands of the stomach, may be the place with the most pronounced probability of developing atrophic and dysplastic processes.
The purpose of this study was to establish the significance of histological changes in the gastric mucosa in the region of the incisura angularis to assess the degree of inflammation activity and the stage of atrophic gastritis.

Aims & Methods

1146 patients (916 women and 230 men) with clinical manifestations of chronic gastritis aged 20 to 84 years were examined. Most patients were represented in the age group from 50 to 70 years (54.6%). Biopsy material was obtained during endoscopic examination in accordance with the OLGA protocol. Histological assessment of the degree of inflammation activity and the stage of atrophy was carried out according to the standard OLGA protocol. Then the same samples were evaluated without taking into account histological changes in the incisura angularis.

Results

During histological examination more frequently (73.2%) was detected the mild severity of inflammation in gastric mucosa (grade II according to the OLGA system). This score practically did not change if the biopsy from the incisura angularis was not tested. Severe stages of gastric mucosa atrophy (stages III and IV according to the OLGA system) were detected in 465 patients (40.58%). If changes in the incisura angularis were not taken into account, then severe stages of atrophy (III and IV) were detected in 460 patients (40.1%). In total, changes in the assessment of the stage of atrophy occurred in 53 patients (4.62%), and more often this was observed in patients with stages I and II of atrophy. Only in 8 patients stage IV of atrophy was changed to III, and in 3 patients stage III was changed to stage II. Thus the stage of atrophy was changed in less than 0,5% of patients in groups with severe atrophy if the samples from the incisura angularis were excluded from the examination.

Conclusion

Evaluation of the histological changes in the gastric mucosa from the incisura angularis does not significantly affect the assessment of the grade and stage of chronic gastritis according to the OLGA system.

References

Rugge M, Genta RM. Staging and grading of chronic gastritis. Human Pathology (2005) 36, 228– 233

Disclosure

This study was conducted within the healthcare research project “Epidemiological study of Helicobacter pylori infection prevalence in Moscow” funded by Autonomous non-profit organization "Moscow Center for Innovative Technologies in Healthcare" administered by the Moscow Healthcare Department. Grant No. 0903-1/22.