Introduction

Disorders of gut brain interaction (DGBIs) is a group of diseases with relatively high prevalence. One of the most common is functional dyspepsia. It has been repeatedly reported that university students tend to have higher prevalence of this disease than general population. Study at medical school is associated with high degree of stress and this could be accumulated during the passing years. As many other factors could affect the symptomatology, the best way to test this hypothesis is to perform a prospective cohort study following one particular group of students over the years.

Aims & Methods

The aim of this study is to evaluate the prevalence of symptoms of functional dyspepsia in selected cohort overtime. This is a prospective, observational study. The observed group were students of medicine from their 1^stto 3^rd year of study. Acquisition of the data was performed by questionnaires. The diagnosis was made by using ROME IV criteria for DGBI. Additional information was obtained from STAX1 and STAX2 validated questionnaires (STAI-X1 shows how the patient feel while answering the questionnaire (anxiety as a state) and STAI-X2 is based on how the patient feel overall (anxiety as a personality trait)) and Beck depression inventory. The measurement was performed in the middle of the school year, every October (2021 to 2023).

Results

Initially 121 students from first year agreed to participate in the study and filled out the questionary. Subsequently the response rate for 2^nd year was 67.8 % and for 3^rd 73%. The symptoms of Functional Dyspepsia were present in 14.9% of participants from 1^st year, 13.4% from 2^nd year and 14.6% from 3^rd year. The cumulative cohort average of STAX 1 was 45.5 points for 1^st year, 46.5 points for 2^nd year and 46.2 points for 3^rd year. The cumulative cohort average of STAX 2 was 47.7 points for 1^st year, 46.2 points for 2^nd year and 46.8 points for 3^rd year. The cumulative cohort average of Beck depression inventory was 8.7 points for 1^st year, 8.8 points for 2^nd year and 8.4 points for 3^rd year. The rate of smoking was 7.4 % of participants from 1^st year, 13.4% participants from 2^nd year and 14.6% from 3^rd year.

Conclusion

The results of this prospective cohort observational study shows that the symptoms of Functional Dyspepsia are highly prevalent among medical students and this varies only insignificantly over time. The probands in average showed no signs of depression however the average levels of anxiety and stress were high during all 3 years. This could be associated with significant rise of smokers within the cohort during the observation period.

Introduction

The diagnosis of non-calcific chronic pancreatitis (CP) is challenging due to the limited accuracy of available diagnostic methods. Endoscopic ultrasound (EUS) is currently considered the most accurate method for the diagnosis of the disease, but age-related changes may affect this accuracy. In this setting, EUS-guided elastography may play a relevant role by quantifying the degree of pancreatic fibrosis, thus optimizing the diagnostic accuracy of the technique.

Aims & Methods

The aim of our study was to evaluate whether EUS-guided elastographic evaluation of the pancreas in patients with suspected CP is affected by patient age.
METHODS: Prospective comparative study of patients undergoing EUS-guided elastography for the evaluation of non-calcific CP. Procedures were performed with Fujifilm linear echoendoscopes attached to the Arietta 850 ultrasound system. The number of EUS criteria for CP according to the Rosemont classification was evaluated. The degree of pancreatic fibrosis was quantified by measuring the strain histogram (SH) and strain ratio (SR). For the evaluation of SH, an area of the pancreatic body was selected, and for the analysis of SR, the same area was selected (area A), and a soft extrapancreatic area was selected as a reference (B), with the quotient B/A being the result. Data are presented as mean ± standard deviation or median and range for quantitative variables and as percentages for categorical variables. Associations between categorical variables were tested using Fisher's exact test or chi-squared test, as appropriate. Quantitative variables were analyzed by ANOVA, and the correlation between SH and SR with Rosemont classification was analyzed by logistic regression. The Spearman test was used to assess the correlation between non-parametric variables.

Results

The study included 284 patients with a mean age of 49.8 years (range 17-85), 142 males. Normal pancreas on EUS was described in 43 patients (15.1%), indeterminate changes for CP in 110 (38.7%), and suggestive findings for CP in 131 (46.1%) according to the Rosemont classification. A statistically significant positive correlation was found between age and the number of EUS criteria according to the Rosemont classification for CP, regardless of etiology (r=0.127, p=0.03), as well as in patients without risk factors (idiopathic CP) (r=0.383, p=0.008). However, no significant correlation was observed between age and EUS elastography (neither SR nor SH) in any of the patient groups.

Conclusion

The evaluation of pancreatic fibrosis by EUS-guided elastography is not influenced by the age of the patients and is therefore accurate for the evaluation of CP.

Disclosure

Julio Iglesias-Garcia, international advisor for Fujifilm, Boston-Scientific, Viatris
Yessica Dominguez-Novoa, international advisor for Fujifilm, Viatris
Jose Lariño-Noia, international advisor for Fujifilm, Boston Scientific, Viatris
J. Enrique Domínguez, international advisor for Boston Scientific, Viatris

Introduction

Pancreatic pseudocyst (PPC) is a well defined local complication of pancreatitis. It has been reported in 8-41% of patients with history of pancreatitis in children¹. In past, surgical technique was treatment of choice for PPC drainage², however with advancements in endoscopic interventions, endoscopic ultrasound (EUS) guided PPC drainage is preferred in present era. Limited literature is available for EUS guided PPC drainage in pediatrics, owing to structure of echo-endoscope due to its rigid tip³, need of anesthesia and endoscopic skills. This study is one of the largest retrospective data⁴ in which we have shared experience of last 10 years for EUS guided PPC drainage from a tertiary care center of Pakistan.

Aims & Methods

This study aimed to evaluate the safety of EUS-guided PPC drainage in a large paediatric cohort (≤18 years) in Karachi, Pakistan, and assess technical and clinical success.
We retrospectively reviewed the charts of patients ≤18 years who underwent EUS-guided PPC drainage from 2015 to 2024 at the Sindh Institute of Advanced Gastroenterology, a tertiary care centre in Karachi, Pakistan. Data collected include patient demographics, aetiology of pancreatitis, PPC characteristics, procedural details, and outcomes. Technical success was defined as successful stent placement across the cyst gastrostomy. Clinical success included PPC resolution and symptom improvement.

Results

28 patients were referred for EUS-guided PPC drainage, 7 patients had no symptoms when presented, so 21 patients underwent EUS-guided PPC drainage. All patients were given general anesthesia by a pediatric anesthetist, and the airway was secured by endotracheal intubation to avoid the risk of aspiration. out of 21 patients,11 were male, with ages ranging from 6 to 18 years (Mean age 14.00± 3.25 years). 11 patients underwent EUS-guided complete aspiration of pseudocyst, with average pseudocyst size of 4.27 X3.93 cm, ranged from 2X1.2cm to 6.7 x5.6 cm. 10 patients underwent EUS-guided pseudocyst drainage via stent placement. The average size of PPC in this group was 8.39 X 8.02 cm, ranged from 6 X5 cm to 14X10cm. 8 pseudocysts were located along the pancreatic body region, 8 were located along the head and neck, and 5 were located near the tail region. Two Double pig tail plastic stents (DPPS) of 7fr 4cm were placed in 9 patients and 7fr 6cm in one patient transmurally into the cyst-gastrostomy tract, whereas LAMS hot axios 10x20 mm was placed in one patient only. One of the patients had a recurrence of pseudocyst with symptoms after 3 months, hence needing repeat pseudocyst drainage. One patient had displacement of DPPS. None of the patients developed major complications.

Conclusion

Endoscopy guided pancreatic pseudocyst drainage is safe and effective in pediatric population, however this procedure should be done by trained and experienced endoscopists under general anesthesia by pediatric anesthetist and EUS guided technique should be preferred over conventional technique of PPC drainage.

References

1.Park, A., Latif, S.U., Shah, A.U., Tian, J., Werlin, S., Hsiao, A., Pashankar, D., Bhandari, V., Nagar, A. and Husain, S.Z. (2009), Changing Referral Trends of Acute Pancreatitis in Children: A 12-year Single-center Analysis. Journal of Pediatric Gastroenterology and Nutrition, 49: 316-322. https://doi.org/10.1097/MPG.0b013e31818d7db3
2.Szakó L, Mátrai P, Hegyi P, Pécsi D, Gyöngyi Z, Csupor D, Bajor J, Erőss B, Mikó A, Szakács Z, Dobszai D. Endoscopic and surgical drainage for pancreatic fluid collections are better than percutaneous drainage: Meta-analysis. Pancreatology. 2020 Jan 1;20(1):132-41
3.Thomson M, Tringali A, Dumonceau JM, Tavares M, Tabbers MM, Furlano R, Spaander M, Hassan C, Tzvinikos C, Ijsselstijn H, Viala J. Paediatric gastrointestinal endoscopy: European society for paediatric gastroenterology hepatology and nutrition and European society of gastrointestinal endoscopy guidelines. Journal of pediatric gastroenterology and nutrition. 2017 Jan 1;64(1):133-53
4.Nabi Z, Talukdar R, Lakhtakia S, Reddy DN. Outcomes of Endoscopic Drainage in Children with Pancreatic Fluid Collections: A Systematic Review and Meta-Analysis. Pediatr Gastroenterol Hepatol Nutr. 2022 May;25(3):251-262. doi: 10.5223/pghn.2022.25.3.251. Epub 2022 May 9. PMID: 35611379; PMCID: PMC9110851.

Introduction

Pancreatic fibrosis (PF) is a prominent histological feature of chronic pancreatitis and influences on vast majority of pancreatic disorders. So, PF early diagnosis gives a great opportunity to be a part of the strategy for preventing pancreatic diseases progression. It makes non-invasive PF assessment especially via biomarkers level measurement research perspective.

Aims & Methods

Aim was to evaluate the possibility of biomarkers levels measurement in PF grade assessment.
Methods. We measured interleukin-10 (IL-10) and interleukin-36 (IL-36), matrix metalloproteinase-1 (MMP-1) and matrix metalloproteinase-9 (MMP-9), fibronectin (FN) and hyaluronic acid (HA) plasma levels from 165 patient who underwent surgery from April 2022 to February 2024 due to pancreatic tumors and advanced chronic pancreatitis. We included 69 (41.8%) male and 96 (58.2%) female patients, mean age was 57.91±13.5 (25-89). Serum levels of specified biomarkers were determined by enzyme immunoassay using commercial kits; data registration performed was carried out on a semi-automatic analyzer. PF morphological grade was assessed according to Klöppel & Maillet’s scoring system [1] and scaled into three grades: mild, moderate and severe PF.
This study was conducted within the healthcare research project “Assessment of pancreatic fibrosis as a prognostic factor for its diseases course” funded by Autonomous non-profit organization "Moscow Center for Innovative Technologies in Healthcare" administered by the Moscow Healthcare Department.

Results

Plasma FN (pFN) level was significantly (p=0.029) higher in patients with mild PF (pFN=110.7±72.7 μg/mL), than in patients with severe PF (pFN=74.9±32.8 μg/mL). The median pFN levels were significantly varied in groups with different grades of intralobular PF (p<0.05), but not in groups divided by perilobular PF grade (p>0.05). Moreover, pFN level significantly negatively correlated with PF integrative grade (Spearmen’s rho = -0.21, p=0.007). Regarding IL-10, IL36, MMP-1, MMP-9 and HA levels, there were no significant differences either in patients with different PF integrative grade, or in groups divided by perilobular and intralobular PF (p>0.05). We revealed no significant correlations between specified biomarkers levels and PF grade (p>0.05).

Conclusion

The FN serum level significantly decreased in patients with severe PF in contrast to patients with mild PF who had comparatively higher serum FN level. Oppositely, IL-10, IL36, MMP-1, MMP-9 and HA had shown no effect in PF grade assessment. It could be useful for noninvasive pancreatic fibrosis diagnosis and even for patients’ selection for advanced diagnostics.

References

1 Esposito I, Hruban RH, Verbeke C, et al. Guidelines on the histopathology of chronic pancreatitis. Recommendations from the working group for the international consensus guidelines for chronic pancreatitis in collaboration with the International Association of Pancreatology, the American Pancreatic Association, the Japan Pancreas Society, and the European Pancreatic Club. Pancreatology. 2020;20(4):586-593. doi:10.1016/j.pan.2020.04.009

Introduction

Lumen-apposing metal stents (LAMSs) have significantly advanced endoscopic ultrasound (EUS)-guided treatment of pancreatic fluid collections (PFCs). However, their impact on clinical outcomes in real-world settings remains incompletely understood.

Aims & Methods

Using the Diagnosis Procedure Combination database—a nationwide inpatient database in Japan where LAMSs were approved in 2018—we identified 5,885 patients who underwent EUS-guided treatment for PFCs at 550 hospitals between 2010 and 2023. We examined the association between treatment period (before vs. after LAMS implementation at each hospital) and clinical outcomes. Multivariable logistic regression analyses were conducted to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for in-hospital mortality, bleeding, length of stay, and total healthcare costs, adjusting for potential confounders.

Results

Compared with patients treated in the pre-LAMS period, those treated in the post-LAMS period had a significantly higher risk of bleeding (adjusted OR, 1.56; 95% CI, 1.35–1.81). Additionally, the post-LAMS period was associated with an increase of approximately $3,300 (USD) in total healthcare costs, with an adjusted OR for being in the highest quartile of total costs of 1.55 (95% CI, 1.34–1.79). There was no significant difference in the risk of in-hospital mortality (adjusted OR, 1.21; 95% CI, 0.95–1.55) or prolonged hospitalisation (adjusted OR for top quartile, 0.98; 95% CI, 0.86–1.12).

Conclusion

The introduction of LAMSs was associated with an increased risk of bleeding and higher healthcare costs, without significant improvements in mortality or hospital stay duration. These findings suggest that routine use of LAMSs for EUS-guided PFC treatment should be reconsidered.

Disclosure

HI declares research funding from Boston Scientific Japan, Fujifilm, and Piolax Medical Devices; honoraria from Boston Scientific Japan, Century Medical, Create Medic, Fujifilm, Gadelius Medical, Hitachi Medical, Japan Lifeline, Kaneka, Kawasumi Laboratories, Olympus Medical, Piolax Medical Devices, Sumitomo Bakelite, UMIDAS, and Zeon Medical; and contributions from Boston Scientific Japan, Gadelius Medical, Japan Lifeline, and Zeon Medical. YN declares research funding from Boston Scientific Japan, Century Medical, Fujifilm, Gadelius Medical, HOYA Pentax Medical, Hitachi Medical, Kaneka, and Medico’s Hirata; and honoraria from Boston Scientific Japan, Fujifilm, Gadelius Medical, Hitachi Medical, J-MIT, Medico’s Hirata, and Olympus Medical. This work was not supported by any of those companies. No other conflicts of interest exist. The other authors declare that they have no conflicts of interest.

Introduction

​Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related deaths, with a five-year survival rate under 10% [1]. Its lethality stems from its aggressive progression and strong chemotherapy resistance, both closely linked to epithelial-mesenchymal transition (EMT). EMT enables epithelial cells to gain migratory mesenchymal traits and is regulated by transcription factors such as SNAIL, SLUG, ZEB1/2, and TWIST [2]. Among these, SNAIL plays a major role in metastasis [3], while ZEB1 is associated with poor prognosis [4]. EMT is tightly modulated by networks including ELAVL1, which encodes the RNA-binding protein HuR. HuR stabilizes mRNAs by binding AU-rich elements (AREs) in their 3′ untranslated regions (3′UTRs), promoting their expression [5].

Aims & Methods

This study aimed to identify post-transcriptional interactions between ELAVL1 and EMT-related genes and assess their prognostic value in PDAC. mRNA was extracted from cancerous and adjacent normal tissues (n=65), converted to cDNA, and analyzed by RT-PCR. BxPC-3, MiaPaCa-2, and Su.86.86 cell lines were cultured under standard conditions. Immunoprecipitation was performed on 1–2×10⁷ cells using a mouse monoclonal anti-HuR antibody, with IgG as control. qRT-PCR assessed mRNA enrichment. Binding sites were annotated using CISBP-RNA, considering only RNAdirect-confirmed 3′UTR motifs. Target 3′UTR sequences were retrieved from GENCODE V47. Statistical analysis was performed using GraphPad Prism, applying the Wilcoxon signed-rank test, Kruskal-Wallis test with Dunn’s correction, and Spearman correlation. Data were presented as median ± interquartile range, with p<0.05 considered significant.

Results

​Expression levels of EMT-related genes and ELAVL1 varied according to survival outcomes. In short-term survivors (1–12 months), SNAIL and SLUG were significantly upregulated (2.19- and 1.92-fold), while ZEB2 was downregulated (0.65-fold). Medium-term survivors (13–35 months) showed reduced ZEB1 (0.53), SNAIL (0.30), SLUG (0.35), and TWIST (0.68). Long-term survivors (36–125 months) had the lowest levels of ZEB1 (0.24), ZEB2 (0.50), SLUG (0.24), TWIST (0.35), and ELAVL1 (0.72). ELAVL1 showed strong positive correlations with ZEB1, SNAIL, and SLUG (r = 0.74–0.76), whereas overall survival was weakly negatively correlated with the expression of ZEB1, SNAIL, SLUG, and TWIST (r = -0.25 to -0.32). Although ZEB1, SNAIL, and TWIST did not show significant survival differences individually, low SLUG predicted better early survival (36 vs. 15 months, p = 0.0278). ELAVL1 expression was stratified as high and low. High ELAVL1 corresponded to a 71.65-fold increase in ZEB1, whereas high ZEB1 reduced ELAVL1 by 96.1%. High ELAVL1 also led to a 312.35-fold increase in SNAIL, while low ELAVL1 still supported elevated SNAIL expression (8.45-fold). High SNAIL expression reduced ELAVL1 by 90%, though simultaneous high expression of both resulted in a 3.71-fold ELAVL1 increase. High SLUG reduced ELAVL1 by 93%, whereas low SLUG led to a 198.11-fold increase. Binding site analysis revealed ELAVL1 targets within 3′UTRs: 34 in ZEB1, 1 in SNAIL, and 9 in SLUG.

Conclusion

ELAVL1 (HuR) likely plays a central role in regulating EMT in PDAC through stabilization of key transcription factor mRNAs. High levels of ELAVL1, SNAIL, SLUG, and ZEB1 were associated with worse outcomes, particularly in short-term survivors. Conversely, low expression of SLUG was linked to improved survival. The strong correlations and validated binding sites suggest ELAVL1 as a promising prognostic biomarker and potential therapeutic target in PDAC.

References

1. Nakaoka K, Ohno E, Kawabe N, Kuzuya T, Funasaka K, Nakagawa Y, et al. Current status of the diagnosis of early-stage pancreatic ductal adenocarcinoma. Diagnostics (Basel). 2023;13(2).
2. Kaşıkcı E, Aydemir E, Bayrak ÖF, Şahin F. Inhibition of migration, invasion and drug resistance of pancreatic adenocarcinoma cells - role of Snail, Slug and Twist and small molecule inhibitors. Onco Targets Ther. 2020;13:5763-77.
3. Tang X, Sui X, Weng L, Liu Y. SNAIL1: Linking tumor metastasis to immune evasion. Front Immunol. 2021;12:724200.
4. Liu M, Zhang Y, Yang J, Zhan H, Zhou Z, Jiang Y, et al. Zinc-dependent regulation of ZEB1 and YAP1 coactivation promotes epithelial-mesenchymal transition plasticity and metastasis in pancreatic cancer. Gastroenterology. 2021;160(5):1771-1783.e1.
5. Majumder M, Chakraborty P, Mohan S, Mehrotra S, Palanisamy V. HuR as a molecular target for cancer therapeutics and immune-related disorders. Adv Drug Deliv Rev. 2022;188(114442):114442.