Introduction

Vagal nerve injury may lead to symptoms of nausea, vomiting, abdominal discomfort, and bloating. Be it by injury or an infiltrative process, vagal nerve function is difficult to assess. Measuring pancreatic polypeptide (PP) following a sham meal may serve as a reasonable surrogate marker of vagal nerve function. PP is released in response to eating and may correlate with slow gastric emptying. Our aim is to assess vagal nerve integrity using sham feeding with measurement of PP, in addition to evaluating the relationship of symptoms with PP levels and gastric emptying.

Aims & Methods

This was a retrospective study of patients who underwent a sham feeding study at Mayo Clinic Florida from 2018 to 2023. We collected demographic and clinical data, sham feeding results, the indication for the study, and gastric emptying data. A 50 % increase in PP level within 30 mins compared to baseline after sham feeding was considered normal. A gastric emptying scan was classified as delayed if <75% of the material emptied at 4 hours.

Results

29 patients were included (58.6% women) with a mean age of 57.3 years. Most patients were white (n=24), and the mean BMI was 27.9 kg/m². The most common reason to request a sham feeding study was abdominal pain (7, 24.1%), gastroesophageal reflux (GER) (6, 20.7%) and chronic nausea and vomiting (6, 20.7%). The main GI symptoms were nausea and vomiting (13, 44.8%) and diarrhea (11, 37.9%). The average weight loss from the onset of symptoms was 31 lb. 24 of 29 included patients had a history of abdominal surgery, with hiatal hernia repair (HHR) and HHR with Nissen fundoplication being the two most common surgeries (5, 17.2%). 20 of 29 studied patients (69.0%) had an abnormal sham feeding study and 48.1% of the patients who underwent gastric empty studies were found to have delayed gastric emptying. The mean baseline PP level of normal vs abnormal was 102.88 pg/mL and 226.4 pg/mL, respectively (p=0.21). The mean peak PP level of normal vs abnormal was 195.22 pg/mL and 245 pg/mL, respectively (p=0.68). Among the 20 patients with an abnormal sham feeding study, ten had delayed gastric emptying. Symptoms of nausea and vomiting were found to have a robust correlation with a positive sham feeding result (12, 92%), compared with gastric emptying scintigraphy (8, 61.5%). There was no correlation between sham feeding result with symptoms of abdominal pain and GER. The care after apparent vagus nerve injury required significant medical resources, including an average of 3.5 visits and 5.7 tests per patient to evaluate key GI symptoms.

Conclusion

Sham feeding is an underused method to measure vagus nerve injury. It is safe and easy to perform. PP levels measured during sham feeding were consistently abnormal in patients with predominant symptoms of nausea and vomiting after foregut surgery while the correlation between gastric emptying measured using scintigraphy and gastroparesis symptoms was not significant. Interestingly, there was limited correlation between scintigraphy gastric emptying results and outcomes of sham feeding. Our research highlights the significant medical and financial burden evaluating patients with symptoms after foregut surgery. Larger prospective studies are needed to better quantify the relationship between PP levels and gastric emptying in patients with prior foregut surgery who remain symptomatic.

Introduction

Functional Dyspepsia (FD), a common disorder of gut-brain interaction [1], is associated with alterations in gastric accommodation, gastric emptying, gastric sensitivity, gastroduodenal permeability, and the gut microbiome. Resilience, the ability to maintain function under personal or physical stress, may play a role in the development of FD, although no studies have evaluated this theory. We hypothesize that FD patients have lower resilience than the general population, which may lead to a new therapeutic target.

Aims & Methods

This prospective questionnaire study compared patients with FD (Rome IV criteria) with internal medicine clinic patients without dyspepsia at a tertiary referral center. Participants completed the FD symptom severity score [2], Brief Resilience Scale (BRS) [3], Connor-Davidson Resilience Scale (CDRS) [4], hospital anxiety and depression scale (HADS) [5], early childhood adverse life event questionnaire [6], and perceived stress score [7]. Questionnaires were distributed to clinic patients meeting inclusion/exclusion criteria.

Results

38 FD (mean age 43 years old, 87% female) and 31 control (mean age 57 years old, 39% female) patients completed the survey. FD patients exhibited lower resilience on the CDRS (96.83 vs. 90.26, P<0.04, CI -12.93 to -0.21) but not on the BRS (3.018 vs. 3.022, P<0.96, CI -0.15 to 0.13). FD patients and controls scored no different on the HADS anxiety index (17.05 vs. 18.38, P<0.064, CI -2.74 to 0.08) and depression scores (P<0.14, CI -0.21 to 1.5). The FD group reported "high" perceived psychological stress while the control group reported a “moderate” level (P<0.004, CI 2.002 to 9.827). In childhood, FD patients had significantly more adverse childhood events (29.3% vs. 15%, P<0.004, CI 0.05 to 0.25). FD patients were more likely to have been exposed to a household member suffering from a psychiatric illness compared to control patients (47% vs. 20%, P<0.049, CI 0.001 to 0.5). FD patients were also more likely to report psychological abuse in childhood (53% vs. 17%, P<0.03, CI 0.034 to 0.67). No other significant differences were found in types of early childhood trauma including physical abuse, familial substance abuse, witnessed maternal violence, or criminal behavior by a household member.

Conclusion

This novel, prospective questionnaire pilot study shows that FD patients have lower resilience compared to the general outpatient population on the CDRS. The long-term symptoms of FD may further decrease resilience. While anxiety and psychological stress are not strongly associated with FD, the significant exposure to childhood household members with a psychiatric diagnosis and significantly higher prevalence of self reported psychological abuse may explain the higher prevalence of antidepressant use in this population, especially considering the significantly higher level of self perceived psychological stress [8]. Otherwise, early childhood trauma appears similar between FD patients and patients without FD and is thus not likely to influence resilience markers. Understanding the contribution of resilience to development of FD may lead to therapies enhancing resilience, improving symptoms, and patient well-being.

References

1. El-Serag HB, Talley NJ. Systemic review: The prevalence and clinical course of functional dyspepsia. Aliment Pharmacol Ther. 2004;19:643-654.
2. Taylor F, Higgins S, Carson RT, et al. Development of a symptom-focused patient-reported outcome measure for functional dyspepsia: the functional dyspepsia symptom diary (FDSD). Am J Gastroenterol. 2018 Jan,113(1):39-48.
3. Smith BW, Dalen J, Wiggins K, et al. The brief resilience scale: assessing the ability to bounce back. Int J Behav Med. 2008;15(3):194-200
4. Connor KM & Davidson JR. 2003. Development of a new resilience scale: The Connor-Davidson Resilience Scale (CD-RISC). Depress. Anxiety, 18; 76-82
5. Zigmond AS & Snaith RP. 1983. The hospital anxiety and depression scale. Acta Psychiatrica Scandinavica, 67: 361-370
6. Felitti VJ, Andra RF, Nordenburg D, et al. Relationship of childhood abuse and household dysfunction to many of the causes of death in adults. The adverse childhood experiences (ACE) study. Am J Prev Med. 1998 May;14(4):245-58
7. Cohen S, Kamarck T, Mermelstein R. A global measure of perceived stress. J Health Soc Behav. 1983 Dec;24(4):385-96.
8. Esterita T, Dewi S, Suryatenggara FG, Glenardi G, et al. Association of Functional Dyspepsia with Depression and Anxiety: A Systematic Review. J Gastrointestin Liver Dis. 2021 Jun 18;30(2):259-266.

Introduction

Gastroparesis (GP) is a chronic motility disorder characterized by recurrent upper gastrointestinal (GI) symptoms, namely early satiety, nausea and vomiting, in the absence of a mechanical obstruction. Functional Lumen Imaging Probe (FLIP) is a potential game-changer in anatomical sphincter assessment. Recently, wide prospective trials[1] and a randomized sham-controlled study[2] implemented FLIP to predict response of pyloric-targeted treatments. This has prompted the need for a comprehensive analysis of available FLIP data in GP.

Aims & Methods

The aim of this systematic review was to investigate FLIP role in GP. Meta analysis of normative values and treatment comparative outcomes was also performed. A systematic search was performed until May 2024 on 4 major databases (Pubmed-MEDLINE, Embase, Web of Science, Cochrane). Studies on post-oncological/bariatric surgery gastroparesis were excluded. Pooled baseline mean of FLIP metrics and mean differences (MDs) pre vs post-treatment were calculated. In addition to estimate clinically meaningful normative values for GP, upper-limit reference ranges were estimated by pooled standard deviations (SDs) implementing the formula pooled mean ± 1.96 × pooled SD. Random effects meta-analysis with Knapp-Hartung correction for 95% confidence intervals (CIs) adjustment and I² statistics with subgroup analysis to address heterogeneity were performed.

Results

Twenty studies (N= 805 patients) were included. The majority focused on treatment response, particularly pyloromyotomy. The most assessed FLIP metrics were distensibility index (DI) and cross-sectional area (CSA). Three studies (on 7 total) reported a positive correlation between DI and CSA with specific symptoms (dyspepsia spectrum and nausea/vomiting) and their severity at baseline. Ten studies (on 15 total) studies showed an association between FLIP parameters with clinical response. Pooled mean DI ranged from 7.5 to 8.9 mm²/mmHg and CSA from 85.5 to 195.6 mm² at baseline. Minimum diameter (Dmin) ranged between 10.6 and 16.5 mm while Pressure (P) between 14.8 and 34.5 mmHg (table 1.). Upper-limit normative values for GP ranged from 173-317 mm² for CSA, 17-27 mm for Dmin, 32-64 mmHg for P (between 30-50 mL of fill volumes), while for DI at 50mL the reference limit attested at 21.5 mm²/mmHg. Comparing pre-and post-treatment response, MD of 2.5 mm²/mmHg (I² 24%) for DI at 50 mL, 46.7 mm² (I² 47%) and 68.8 mm² (I² 0%) for CSA at 40 and 50 mL respectively, were statistically significant.

Table 1. FLIP metrics pooled mean values at different fill volumes at baseline in gastroparesis patients

Conclusion

This is the first systematic effort in gathering evidence on FLIP in gastroparesis. CSA and DI significantly changed after pylorus-targeted treatments. Normative values displayed substantial heterogeneity and wide CIs. The cut-off of 10 mm²/mmHg for DI seems feasible to categorize patients to be addressed to pylorus-targeted treatments. Further studies to calculate prediction ability of this cut-off are warranted.

References

1. Jacques J, Pagnon L, Hure F, Legros R, Crepin S, Fauchais A-L, et al. Peroral endoscopic pyloromyotomy is efficacious and safe for refractory gastroparesis: prospective trial with assessment of pyloric function. Endoscopy. 2019;51(1):40-9.
2. Martinek J, Hustak R, Mares J, Vackova Z, Spicak J, Kieslichova E, et al. Endoscopic pyloromyotomy for the treatment of severe and refractory gastroparesis: a pilot, randomised, sham-controlled trial. Gut. 2022;71(11):2170-8.

Disclosure

E.V. received speaker and/or consulting fees from Sanofi/Regeneron, Falk Pharma, Apollo Therapeutics, and Aurora Biofarma. AJB received research funding from BMS, Sanofi/Regeneron, SST, and Dr. Falk Pharma and received speaker and/or consulting fees from Uniquity, Laborie, Medtronic, BMS, Dr. Falk Pharma, Calypso Biotech, Eupraxia, Aqilion, Alimentiv, Sanofi/Regeneron, Uniquity, Reckitt, AlfaSigma and AstraZeneca. All other authors did not have any disclosures.

Introduction

Noncardiac chest pain (NCCP) is a challenging condition associated with decreased quality of life, diagnostic uncertainty, and a high healthcare burden. The most common gastrointestinal causes are gastroesophageal reflux disease (GERD), functional chest pain, and spastic esophageal motor disorders. Effective treatments are lacking particularly for patients who do not respond to proton pump inhibitors. Virtual reality (VR), an innovative non-invasive tool providing multi-sensory stimulation through a head mounted display, has demonstrated usefulness in treating acute and chronic pain, anxiety, and other gastrointestinal disorders. The objective of this study was to assess the feasibility of virtual reality for the treatment of NCCP.

Aims & Methods

This was a feasibility study of 11 adult patients with NCCP, defined as persistent angina-like chest pain despite the exclusion of a cardiac source. All patients underwent esophagogastroduodenoscopy (EGD) to exclude treatable, secondary gastrointestinal causes. Participants were provided a VR headset preloaded with three-dimensional immersive environments including relaxation simulations and guided diaphragmatic breathing. Participants were asked to use the headset at least 15 consecutive minutes daily for 14 days. The primary objective was to assess the overall feasibility of VR for the treatment of NCCP and challenges that may impact the performance of a future clinical trial. As a secondary objective, we assessed the effectiveness of VR to improve pain severity, gastrointestinal symptoms, hypervigilance, quality of life, depression, anxiety, and resilience through validated questionnaires. Continuous variables were compared with the paired-samples t-test and categorical variables with McNemar’s test.

Results

Eleven patients completed the study with a median age 59 (range 44-72) years, 10 (91%) female, and median body mass index 24.9 kg/m² (19.6-28.7). Ten patients had a normal endoscopic appearance of the esophagus, and one patient had Los Angeles grade A esophagitis. All patients had incomplete treatment response to a proton pump inhibitor. There were improved depression scores by the Hospital Anxiety and Depression Scale compared to baseline after one (median 4 vs. 1, p=0.008) and two weeks (4 vs. 1, p=0.02) and improvement in the composite depression and anxiety score after 2 weeks (10 vs. 6, p=0.009) of the study. There was a trend in improvement of the Esophageal Hypersensitivity and Anxiety Scale although this did not meet statistical significance (43.5 vs. 39.0, 0.097). The virtual reality headset was well-tolerated by all patients without adverse events or safety concerns.

Conclusion

In this two week, prospective feasibility study of patients with NCCP, virtual reality was well tolerated and led to improvement in depression and anxiety scores. These findings provide a foundation for the use of VR for the treatment of NCCP in a larger, prospective randomized controlled trial.