Introduction

Globus pharyngeus is one of the more common Disorder of Gut Brain Interaction (DGBIs). The pathophysiological mechanisms of DGBIs are complex. However, data considering possible cause of globus pharyngeus are scarce. Accumulating evidence indicates that autonomic dysregulation contributes to DGBI but whether this is true for globus is still unknown. The symptoms are often triggered by stress associated with sympathetic overexcitation, however, the mechanisms of sympathetically linked regulation in these disorders, especially in response to stress are incompletely understood.

Aims & Methods

The aim of this study was to assess potential changes of cognitive stress-related sympathetic regulation of different effector responses (skin conductance and alpha-adrenergic vasomotor activity) in patients suffering from globus pharyngeus. Studied population included 15 patients diagnosed with globus and 12 sex- and age-matched healthy controls. All patients were diagnosed according to ROME IV criteria for Disorders of gut brain interaction. Continuous electrodermal activity (EDA) was recorded with sampling frequency of 256 Hz (required by hardware) (FlexComp Infinity Biofeedback, Thought Technology, Canada). The EDA signal was monitored by two dry, Ag-AgCl, bipolar electrodes placed on the middle phalanges of two fingers on the left (non-dominant) hand, and continuous “beat-to-beat” blood pressure (BP) was recorded using Finometer MIDI (FMS, Netherlands) during complex stress response: rest - mental arithmetic test – recovery. Each period lasted 5 minutes. Evaluated parameters: 1) spectral power in low-frequency band of systolic BP variability (LF-SBP) reflecting sympathetic alpha-adrenergic stimulation of vascular smooth muscles, 2) skin conductance level (SCL) calculated as a mean of tonic EDA reflecting sympathetic cholinergic regulation and emotional arousal in response to cognitive stress. Moreover, reactivity of both parameters was calculated.

Results

LF-SBP (reflecting sympathetic function) was normal at baseline, but significantly increased in response to mental arithmetic test in globus group compared to controls (p<0.001), but in recovery phase LF-SBP parameter was without significant between-group changes. Surprisingly, no differences were found in SCL parameter during complex stress response. Reactivity of both parameters was similar and without significant changes.

Conclusion

Our results revealed significantly increased LF-SBP indicating alpha-adrenergic vasomotor overactivity during cognitive stressor associated with a return to basal values in patients with globus pharyngeus compared to controls. In contrast, EDA was without between-group changes during all phases of stress response which may point to remaining emotional and sympathetic arousal in patients with globus pharyngeus. These findings revealing subtle and discrete abnormalities in alpha-adrenergic sympathetic regulatory network evoked only by cognitive stress and can contribute to clarifying the pathomechanisms and psychophysiological pathways leading to sympathetic and emotional dysregulation in patients with globus pharyngeus. We believe that this represents a fundamental step for personalized and specific non-invasive therapy in patients with globus pharyngeus such as biofeedback.
Support: Slovak Scientific Grant Agency [VEGA 1/0048/24]

Introduction

Esophageal Achalasia (EA) is a rare esophageal motility disorder, characterized by impaired peristalsis and incomplete relaxation of the Lower Esophageal Sphincter (LES) in response to swallowing​​​​​. Key symptoms of the disease include dysphagia, food regurgitation, and retrosternal pain, significantly impacting the quality of life (QoL) and often leading patients to restrict their food intake. Consequently, EA patients often adopt self-managed dietary practices that may result in nutritional imbalances and deficiencies, given the lack of specific dietary guidelines.

Aims & Methods

This retrospective study aimed to describe and evaluate the dietary patterns, eating habits, and nutritional status of achalasic patients. Additionally, the secondary aim was to explore potential associations between food rheology and symptomatology. Patients with a manometric diagnosis of EA were recruited from our outpatient gastrointestinal pathophysiology center. Disease severity was assessed with Eckardt Symptoms Score (ESS), symptoms were evaluated with Modular Questionnaire Roma IV and QoL with the MD Anderson Dysphagia Inventory (MDADI). The MDADI outcomes were stratified into severe, moderate, mild and not perceived disability. Patients also filled out a food diary for 15 days, recording ingested food for each meal and symptoms onset. Estimated caloric intake and macronutrient composition were compared to those recommended by the Italian Society of Human Nutrition (SINU).

Results

Forty-three achalasic patients were included (M 24, F 19, mean age 56.7 +- 15.8 yrs). The median BMI was 23.7 (18.8-32.2), 34 patients (79%) had an active disease (ESS ≥ 3). Most patients reported mild to moderate disability (respectively 42% and 35%), while 21% reported severe disability and 2% perceived no disability. Disease activity, measured by ESS, strongly correlated with perceived disability (r= 0.59; p <0.0001), while no significant correlation was found between ESS and BMI. The diary analysis showed a mean caloric intake of 1572±373 kcal versus the estimated needs of 2293,71±374 kcal based on anthropometric parameters and physical activity, resulting in a mean caloric deficit of 720 ± 416 kcal (p<0.0001). Macronutrient analysis also reported an unbalanced distribution: carbohydrates 43.3%±7.3 vs recommended 55-59%, protein 18.2%±4.5 vs 15-18%, total fat 37.6%±7.7 vs 26–27% and fibre 14g±5.2 vs 25-30g. Solid food caused significantly more symptoms than semiliquid and liquid ones: dysphagia (35.5% vs 3.5% vs 5.7%, p<0.0001), chest pain (10% vs 12.1% vs 0.2%, p<0.0001), regurgitation (8.9% vs 1.4% vs 1.9%, p=0.001), cough (5% vs 0.2% vs 0.6%, p=0.0002). Bread, pasta, and pizza (50-60%), fresh fruit (44%), lean meat (39.5%), crackers, snacks, and vegetables (30-35%) were the most commonly reported triggers of dysphagia. Additionally, 60% of patients reported worsened symptoms with cold foods, while 53% reported improvement with hot foods.

Conclusion

This study underscores the significant impact of EA on QoL, influenced by disease activity. Achalasic patients tend to modify their diets to minimize symptoms, favoring easily swallowable soft and fatty foods while reducing intake of solid foods rich in carbohydrates and fiber. Thus, comprehensive nutritional assessment is strongly recommended for EA patients to mitigate dietary imbalances and manage possible deficiencies promptly.

Introduction

‘Inability to Belch’, also called retrograde cricopharyngeal dysfunction (R-CPD), is a syndrome characterized by inability or impaired ability to belch, gurgling noises from the chest or lower neck, thoracic or abdominal pain, bloating and flatulence (1). Although awareness of the disorder is increasing, little is known about its cause, characteristics or epidemiology.
Besides recognition of typical symptoms, high resolution impedance manometry (HRiM) is increasingly used to confirm the diagnosis in suspected cases (2, 3).

Aims & Methods

Our aim was to design a diagnostic questionnaire based on the cardinal symptoms, and to validate this questionnaire against the only available objective diagnostic tool at present, i.e. HRiM with belch provocation test (sparkling water) (2, 3).
The questionnaire was developed based on medical history taking of patients that presented to our center with ‘inability to belch’ (4). Fifteen symptoms were included: inability to belch, gurgling noises, thoracic pain, abdominal pain, nausea, fullness, early satiety, bloating, flatulence, heartburn, regurgitation, frequent or painful hiccups, dysphagia, and difficulty to vomit. These were questioned for frequency, severity, bothersomeness and the trigger or timing at which they occurred. A first draft of the questionnaire was evaluated in a cognitive debriefing of the first three R-CPD patients, after which some clarifying changes were made.
Subsequently, the questionnaire was filled out during HRiM prospectively by R-CPD and control patients, each of whom underwent belch provocation test as described by our group (3).
Wilcoxon signed rank test was used to compare between groups. A logistic model was used to compute probabilities with their 95% confidence interval (CI).

Results

The questionnaire was completed by 17 patients reporting inability to belch, and 47 control patients, during HRiM with belch provocation test. In 13 out of 17 patients (sensitivity 76%, positive likelihood ratio of HRiM: 8.44), R-CPD was confirmed with typical findings on HRiM. The indication for HRiM in control patients was GERD (n=27), dysphagia (n=9), chest pain (n=3), known achalasia (n=2), belching (n=1), globus (n=1) and dyspepsia (n=1). In the control patient group, 4 patients were excluded from further analysis because of abnormalities on HRiM similar to R-CPD (specificity 91%, negative likelihood ratio: 0.26).
Using HRiM as a gold standard, we identified the following questions that were significantly different in R-CPD patients vs. controls: frequency of inability to belch (p <0.001, probability of abnormal HRiM when present: 0.6000 CI 0.380:0.786 ), gurgling noises (p = 0.0019, probability when present 0.4000, CI 0.230:0.597), and dysphagia (p = 0.003, probability when present 0.065, CI 0.016:0.022). Even though these symptoms were often present in R-CPD, chest pain, abdominal pain, nausea, fullness, early satiety, bloating, heartburn, regurgitation, hiccups and vomiting did not differ significantly between both patient groups.

Conclusion

We designed a diagnostic questionnaire to help identifying R-CPD. Based on a comparison between R-CPD patients with a control population with a variety of upper motility disorders, the presence of ‘inability to belch’, gurgling noises; and the absence of dysphagia were significantly different between R-CPD patients and controls.
Pending further validation, this questionnaire provides a basis for developing a scoring system for patients with ‘inability to belch’ and it can be used to explore the epidemiology of this peculiar syndrome.

References

1. Bastian RW, Smithson ML. Inability to Belch and Associated Symptoms Due to Retrograde Cricopharyngeus Dysfunction: Diagnosis and Treatment. OTO Open. 2019;3(1):2473974x19834553.
2. Oude Nijhuis RAB, Snelleman JA, Oors JM, Kessing BF, Heuveling DA, Schuitenmaker JM, et al. The inability to belch syndrome: A study using concurrent high-resolution manometry and impedance monitoring. Neurogastroenterol Motil. 2022;34(5):e14250.
3. Karlien Raymenants FV, Stijn Arnaert, Jan Tack, Tim Vanuytsel, Filip Baert, Lieve Delsupehe, Joris Arts Manometric diagnosis and treatment of retrograde cricopharyngeus dysfunction (R-CPD). United European Gastroenterology Journal. 2023;11.
4. Arnaert S, Arts J, Raymenants K, Baert F, Delsupehe K. Retrograde Cricopharyngeus Dysfunction, a New Motility Disorder: Single Center Case Series and Treatment Results. J Neurogastroenterol Motil. 2024;30(2):177-83.

Introduction

Peroral endoscopic myotomy (POEM) has become a standard endoscopic treatment for patients with achalasia, with many studies reporting on its long-term effectiveness. However, the impact of a patient’s previous surgical history on the long-term outcomes of POEM remains unknown.

Aims & Methods

This study aims to compare the long-term efficacy of POEM in achalasia patients with and without prior surgical interventions. A single center, retrospective review was conducted on achalasia patients who underwent POEM between January 2016 to December 2020. Clinical, demographic, radiographic, endoscopic, and manometric data were collected. Patients with less than two years of follow-up without noted failure were excluded. The analysis compared outcomes between first-time POEM patients (naïve POEM) and those undergoing POEM following failed surgical treatments (redo POEM). The primary outcome was the clinical success rate, defined as an Eckardt Score of 3 or less at final follow-up and no need for additional interventions. Secondary endpoints included the prevalance of postoperative gastroesophageal reflux disesase (GORD), the necessity for acid suppression medications, and additional interventions for achalasia.

Results

Data were collected on 47 naïve POEM and 26 redo POEM patients. After excluding 17 naïve POEM patients and 8 redo POEM patients who did not meet the criteria for long-term follow-up, a total of 30 naïve POEM patients and 18 redo POEM patients were analyzed. In the redo POEM group, 77.8% (14/18) of the patients underwent Heller myotomy with Dor fundoplication, while the surgical details for the remaining patients were unknown. The median length of symptoms was 5 (IQR 3-10) years for naïve patients and 6 (IQR 1.2-17.5) years for redo patients (p=0.29). According to the Chicago classification v4.0, the achalasia subtypes in the naïve POEM group were Type I in 9 patients (30%), Type II in 12 (40%), Type III in 3 (10%), and other types in 6 (20%). For the redo POEM group, subtypes were Type I in 9 patients (50%), Type III in 2 (11.1%), and unspecified in 7 (38.9%). Barium esophagram revealed no significant differences in the maximum diameter between the groups (naïve POEM 45.8 ± 21.4 mm vs. redo POEM 44.9 ± 15.4 mm, p=0.89). Long-term success rates were 76.7% (23/30) in naïve POEM and 83.3% (15/18) in redo POEM, with no significant difference between the groups (p=0.72). Postoperative GORD was noted in 63.3% (19/30) in the naïve POEM versus 67% (12/18) in the redo POEM (p=0.06), with newly prescribed acid suppression medication in 23.3% (7/18) and 55.6% (10/18), respectively (p=0.02). Additional interventions for achalasia were required in 10% (3/30) in the naïve POEM versus 11.1% (2/18) in the redo POEM, with no significant difference between the groups (p=1.0). In the naïve POEM group, one patient required a second POEM, another was hospitalized due to achalasia recurrence, and a third underwent Heller myotomy with Dor fundoplication. In the redo POEM group, one patient underwent endoscopic balloon dilatation, and another required esophagectomy.

Conclusion

POEM is an effective long-term treatment for achalasia, demonstrating similar success rates in patients undergoing either their first or redo POEM procedures. The overall efficacy and safety profiles support POEM as a recommended treatment for managing achalasia regardless of prior surgical treatment failures.

Introduction

Colorectal cancer (CRC) is one of the most common neoplasms world widely. G-protein coupled receptors (GPCR) affect crucial elements of oncogenesis, such as responses to various endo- and exogenous stimuli (e.g. medications), angiogenesis and forming metastases. The magnitude of GPCR signaling is terminated by regulators of G-protein signaling (RGS), which typically possess GTPase activity. AXIN is an atypical RGS without GTPase function. Its main role is stabilization of β-catenin destruction complex in which it cooperates with adenomatous polyposis coli (APC) and glycogen synthase kinase3 (GSK3). Through this complex, AXIN antagonizes prooncogenic canonical Wnt signaling pathway that depends on β-catenin. On the other hand, recently attention has been paid to the potential tumor-suppressive properties of cannabinoids (CB) which are ligands of Gαi/o-type GPCR – CB1 and CB2.

Aims & Methods

In this project we aim to test the therapeutic potential of simultaneous targeting of AXIN and CB receptors with KYA1797K and WIN 55,212-2 in CRC cell lines (SW480, Caco-2) and non-cancerous enterocytes CCD 841 CoN as comparator. We hypothesize that KYA1797K is effective in monotherapy and in combination with cannabinoids in CRC. Moreover, we expect that stabilization of AXIN does not to weaken the effect of CB receptor ligands.
Cytotoxicity of KYA1797K (1; 10; 100, 300 µM) and WIN 55,212-2 (1; 10; 100 µM) in monotherapies and combined treatment (KYA1797K(10µM)+WIN 55,212-2(10µM) [K+W10] and KYA1797K(100µM)+WIN 55,212-2(10µM)) was assessed using MTT test. Relative genes’ expression was evaluated using quantitative real-time PCR and Western Blot. Statistical analysis included Shapiro-Wilk test, one-way ANOVA with post-hoc Dunnett’s and Tukey’s tests.

Results

Caco-2 cells were insensitive to KYA1797K in monotherapy excluding concentration of 300 µM, for which we observed significant cytotoxicity. Treatment with WIN 55,212-2 in concentration of at least 10 µM in both mono- and combined therapy significantly reduced viability of this cell line. Similar profile of changes was observed in SW480 line, however the strength of observed effect and sensitivity to KYA1797K were higher. In CCD 841 CoN cells significant additive effect of KYA1797K and WIN 55,212-2 was observed for 100 µM with no changes observed for 10 µM. Moreover, we found that treatment with K+W10 causes significant cytotoxicity in cancerous SW480 cells but not in normal enterocytes CCD 841 CoN. Moreover, K+W10 treatment resulted in increased expression of AXIN 1 and 2 in each cell line except AXIN 2 in Caco-2 line, in which opposite effect was observed. The combined treatment decreased CB1 receptors’ expression in all examined cell lines, whereas opposing tendency was observed for CB2. Furthermore, K+W10 treatment led to increased expression of RGS2, 11, APC and GSK-3. At the protein level K+W10 treatment surprisingly tended to decrease β-catenin relative expression. CB2 receptors were significantly more expressed in SW480 than in CCD 841 CoN that was consistent with cytotoxicity results.

Conclusion

AXIN stabilization is a promising new approach in CRC treatment. AXIN stabilization does not weaken CB1 and 2-dependent effects. The combined treatment of AXIN stabilizer and CB agonist may be especially important as life-prolonging therapy for patients with advanced CRC.

Introduction

Capsule endoscopy (VCE) is generally safe, however a subset of patients require confirmation of bowel patency before undergoing the procedure, using a self-dissolvable patency capsule of similar calibre to the video capsule, with interval imaging to confirm excretion. Patency capsule absence on imaging confirms bowel patency. Prucalopride, a 5-HT4 agonist that enhances bowel motility, has been used in VCE to improve completion rates¹, but its use in the context of patency testing remains unknown. Similarly, the role of fasting in improving pass rate is unclear.

Aims & Methods

This study aims to determine whether Prucalopride and fasting enhance the pass rate of patency tests. Data from procedures performed in 3 centers in the Republic of Ireland was reviewed retrospectively. We compared the pass rate in the context of Prucalopride (Group A), fasting (B), and non-fasting (C) states. All patients had an abdominal x-ray between 24-30 hours post-patency capsule ingestion to confirm passage. ANOVA test was used to compare means between all groups, and student t-test between individual groups.

Results

A total of 127 patients were included. Group A (Pruculopride): 59 patients, Group B (fasting, no Prucalopride): 22 patients, Group C (non-fasting, no Prucalopride): 46 patients.
Demographics:

• Group A: 47.5% males and 52.5% females, Group B: 45.5% males and 54.5% females, Group C: 32.6% males and 67.4% females
• Mean age – Group A: 50.3 years (range 18-82), Group B: 48.4 years (24-82), Group C: 47.9 (17-79).

• Appropriate: 80 (63%)
• Inappropriate: 35 (27.6%)
• Undocumented: 12 (9.4%)

• Group A: 36/59 (61%), Group B: 17/22 (77%), Group C: 19/46 (67%).
• ANOVA test f-ratio 4.55, p= 0.012.
• T-test: Group A vs B (61% vs 77%, p=0.087). A vs C (61%vs 67%, p=0.023), B vs C (77% vs 67%, p=0.002).

Conclusion

This study shows that fasting improves patency tests pass rates, but Prucalopride does not. Fasting and subsequent patency capsule ingestion promoting the gastro-ileal reflex is a possible explanation. It is unclear in this study why Prucalopride, a prokinetic and laxative, failed to show an improvement in pass rates despite being shown to improve VCE completion rates in other studies. Longer duration of Prucalopride at split intervals is a potential area for further studies.

References

1. Deding U, Kaalby L, Baatrup G, Kobaek-Larsen M, Thygesen MK, Epstein O, et al. The effect of prucalopride on the completion rate and polyp detection rate of colon capsule endoscopies. Clinical Epidemiology 2022;Volume 14:437–44. doi:10.2147/clep.s353527.

Disclosure

None

Introduction

As no direct comparison between IBD drugs to prevent endoscopic postoperative recurrence (POR) in Crohn’s disease (CD) are available, hierarchizing these therapeutic options remains challenging.

Aims & Methods

The objective of this network meta-analysis was to compare the effectiveness of treatments to prevent endoscopic POR of CD.
We performed a systematic review and network meta-analysis of comparative studies conducted in adults, evaluating a treatment to prevent endoscopic POR after ileocecal resection. The selection of studies was made according to PRISMA guidelines. The primary endpoint was endoscopic POR at 6 months defined as Rutgeerts score ≥ i2.
The network meta-analysis was carried out according to a random effects model. The results are presented as odds ratio (OR) with 95% confidence interval, adjusted for risk factors of POR. The risk of bias of the studies was assessed according to the Cochrane risk-of-bias tool for randomized trials and overall statistical heterogeneity between studies was assessed using τ.
The SUCRA ranking method (surface under the cumulative ranking) was used to rank the treatments.

Results

Twenty studies were included in this network meta-analysis, including a total of 2414 patients. Overall heterogeneity was moderate (τ =0.34). After adjustment for POR risk factors, ustekinumab (OR = 0.23 [0.07-0.70]), vedolizumab (OR = 0.17 [0.05 -0.59]), infliximab (OR = (0.18 [0.36-0.88]) and adalimumab (OR = 0.17 [0.07-0.42]) were superior to placebo to prevent endoscopic POR, contrary to 5-ASA (OR = 0.79 [0.42 -1.48]) and thiopurines (RR = 0.52 [0.22-1.24]) (Table 1). Ustekinumab (OR = 0.29 [0.08-0.99]), vedolizumab (OR = 0.22 [0.06-0.85]), infliximab (OR = (0.23 [0.09-0.54]) and adalimumab (OR = 0.22 [0.08-0.59]) were more effective than 5-ASA in preventing endoscopic POR. Adalimumab (OR = 0.33 [0.15-0.74]) and infliximab (OR = 0.34 [0.13-0.87]) were also more effective than thiopurines.
We observed no difference in efficacy between the 4 biologics (infliximab, adalimumab, ustekinumab and vedolizumab). The SUCRA ranking identified adalimumab (SUCRA = 0.81), infliximab (SUCRA = 0.80), vedolizumab (SUCRA = 0.79) and ustekinumab (SUCRA = 0.72) as the most effective treatments. The probability that thiopurines (SUCRA = 0.41), 5-ASA (SUCRA = 0.24), placebo (SUCRA = 0.16) and antibiotics (SUCRA = 0.08) were significantly higher weak.

Conclusion

This network meta-analysis confirms the efficacy of anti-TNF agents, vedolizumab and ustekinumab in preventing endoscopic CD POR without any difference between them. When prophylactic therapy is indicated, biologics appear as the best therapeutic option to prevent of endoscopic POR. Due to lower effectiveness, the use of 5-ASA and thiopurines should be limited in this situation.

Disclosure

Anthony BUISSON: Consulting fees for Abbvie, Amgen, Arena, Biogen, Celltrion Healthcare, CTMA, Galapagos/Alfa Sigma, GutyCare/Resilience, Janssen, MSD, Nexbiome, Pfizer, Roche, Sandoz, Takeda, Tillotts. And Viatris. Lecture fees for Abbvie, Amgen, Biogen, Celltrion Healthcare, Galapagos/Alfa Sigma, Janssen, Mayoli-Spindler, MSD, Nordic Pharma, Norgine, Pfizer, Roche, Takeda, Tillotts and Vifor Pharma. Research grants from: Abbvie, Celltrion Healthcare, Galapagos/Alfa Sigma, Janssen, Lessaffre, Lilly, Pfizer, Takeda.