Introduction

Endoscopic ultrasound (EUS) emerged as a revolutionary intervention in gastroenterology, it has been extensively utilized among adult patients, however EUS utility in pediatric patients has remained limited due to EUS endoscope design which includes rigidity, diameter, traumatic distal tip, further more complicated by need of Monitored Anesthesia Care (MAC) or General Anesthesia (GA) for intervention which require specialized pediatric anesthesia team[i]. Fewer studies have been conducted so far regarding EUS utility, effectiveness and safety among children, most of the studies have smaller data. Recently, the European Society for Pediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) and the European Society of Gastrointestinal Endoscopy (ESGE) have published joint guidelines for EUS in children which highlights the various indications for EUS in children[ii].In Pakistan, only few endoscopy centers are performing pediatric EUS.

Aims & Methods

This article aims to describe the safety along with technical and clinical success of EUS for both diagnostic and therapeutic purposes among children at a tertiary referral endoscopy center in Pakistan.
Retrospective charts review of patients ≤ 18 years of age who underwent EUS for disgnostic or therapeutic purpose over 10 years, from 2015 to 2024, at Sindh Institute of Advanced Endoscopy and Gastroenterology. This institute was initially working under Civil Hospital Karachi as Endoscopy Suite of S4 Unit. Since May 2023, it has been working as a separate endoscopy unit. This endoscopy center is a referral unit located in the largest city of Pakistan.

Results

A total of 130 patients ≤ 18 years age had EUS, the youngest was 5 years old and 54.3% were male gender. Primary indication for EUS examination included: 35 chronic pancreatitis, 39 pancreatic pseudocyst, 12 pancreatic mass, 3 biliary obstruction with suspected choledochal cyst, 2 liver biopsy, 21 gastrointestinal tract lesions, 6 lymph nodes and 12 other causes. 96 EUS were performed for diagnostic purpose, in which 20 patients underwent fine needle biopsy and 6 underwent fine needle aspiration. Among therapeutic EUS, patients underwent 21 EUS guided pseudocyst drainage, one patient had EUS guided walled off necrosis drainage, 4 patients underwent celiac plexus block referred for pain management of chronic pancreatitis,one patient underwent EUS guided pancreatic duct cannulation and stent placement and one patient had EUS guided randezvous procedure. All therapeutic procedures were performed under general anesthesia whereas diagnostic EUS were performed under monitored anesthesia care. No immediate or early complications were seen.

Conclusion

In this modern era of advanced diagnostic tools and minimally invasive interventions, EUS related procedures are safe and effective in pediatric group of patients too. However, this procedure should be standardized and performed at centers with trained endoscopists and an experienced pediatric anesthesia team.

References

[i] Thomson, M., Tringali, A., Dumonceau, J.-M., Tavares, M., Tabbers, M.M., Furlano, R., Spaander, M., Hassan, C., Tzvinikos, C., Ijsselstijn, H., Viala, J., Dall'Oglio, L., Benninga, M., Orel, R., Vandenplas, Y., Keil, R., Romano, C., Brownstone, E., Hlava, Š., Gerner, P., Dolak, W., Landi, R., Huber, W.D., Everett, S., Vecsei, A., Aabakken, L., Amil-Dias, J. and Zambelli, A. (2017), Paediatric Gastrointestinal Endoscopy. Journal of Pediatric Gastroenterology and Nutrition, 64: 133-153. https://doi.org/10.1097/MPG.0000000000001408.
[ii] Thomson, M., Tringali, A., Dumonceau, J.-M., Tavares, M., Tabbers, M.M., Furlano, R., Spaander, M., Hassan, C., Tzvinikos, C., Ijsselstijn, H., Viala, J., Dall'Oglio, L., Benninga, M., Orel, R., Vandenplas, Y., Keil, R., Romano, C., Brownstone, E., Hlava, Š., Gerner, P., Dolak, W., Landi, R., Huber, W.D., Everett, S., Vecsei, A., Aabakken, L., Amil-Dias, J. and Zambelli, A. (2017), Paediatric Gastrointestinal Endoscopy. Journal of Pediatric Gastroenterology and Nutrition, 64: 133-153. https://doi.org/10.1097/MPG.0000000000001408

Introduction

Malnutrition is a typical complication of pancreatic diseases. Vitamin D (VD) insufficiency or deficiency is present in chronic pancreatitis (CP), leading to increased cardiovascular risk, bone complications, impaired quality of life and increased mortality.

Aims & Methods

The study aimed to determine the prevalence of VD deficiency or insufficiency in patients with CP, and to assess its relationship to CP progression and associated cardiovascular and bone complications. 70 patients (45 males) were enrolled, with a mean age of 54.01±13.46 years. Alcohol abuse was the most common aetiology. Imaging morphological data were assessed by Cambridge classification for CT/MRCP; pancreatic exocrine insufficiency (PEI) - by fecal elastase-1, CP severity - by M-ANNHEIM classification; bone densitometry - by Dual-energy X-ray absorptiometry; and cardiovascular risk - by 10-year risk of mortality scores (SCORE and Framingham Risk Score - FRS) and by the arterial stiffness using pulse wave velocity (PWV) at а.carotis and a.femoralis. Determination of 25-hydroxyvitamin D was performed by a LC-MS/MS method. Vitamin D status was assessed as deficiency (<25 nmol/L), severe insufficiency (25–50 nmol/L), mild insufficiency (50–80nmol/L), and sufficiency (>80 nmol/L). Resting energy expenditure was calculated using the Harris-Benedict formula. Statistical analysis was performed by SPSS.

Results

Mean VD levels were 37.86±24.36 nmol/L (range 3.854–99.874 nmol/L); 26 patients had deficiency; profound insufficiency was found in 25 patients; another 14 were with mild insufficiency, and only 5 patients were in a sufficiency status. We found no significant relation between VD levels and gender. VD levels correlated significantly with BMI but not with symptoms (weight loss, pain and steatorrhea). 12 patients reported no symptoms, however, 10 of them had levels of VD less than 50 nmol/L. Resting energy expenditure correlated significantly with VD levels (r=0.53, p=0.000). In patients with severe structural changes, we observed significantly lower VD levels regardless of etiology (p<0,01). VD levels were lower in patients with PEI, p<0.05. Patients with mild CP by M-ANNHEIM had lower VD levels compared to patients with moderate and advanced CP, p<0.05. We found an association of VD with pancreatolithiasis. At a cut-off of VD 11.95 nmol/L, we verified pancreatic lithiasis with 89.4% sensitivity and 83.3% specificity and AUC of 0.826±0.113 (95% CI, 0.61-1). VD status worsened with increasing the 10-year risk of mortality by both SCORE and FRS, p<0,05. We observed lower vitamin D levels with increasing PWV. Lower VD levels were associated with diabetes mellitus. 35.6% of the investigated patients had osteopenia or osteoporosis. Bone density was affected and significantly decreased in patients with VD deficiency or severe insufficiency. By increasing and optimising the dose of pancreatic enzymes in patients with pancreatic insufficiency, we demonstrated clinical improvement with a significant increase in BMI (p<0.0001) and VD levels, p<0.01.

Conclusion

Most of our patients with CP were VD insufficient. Monitoring of nutritional status in patients with CP is mandatory to prevent the development of malnutrition complications and associated morbidity and mortality. An effort should be the point of a multidisciplinary approach for an up-to-date strategy for patients with pancreatic disorders, ensuring optimal therapeutic results and better quality of life.

Introduction

Pancreatic inflammation is often triggered by sustained intraductal pressure, commonly due to gallstones or endoscopic retrograde cholangiopancreatography (ERCP). In mouse models, transient pressure disrupts tight junction integrity via calcineurin. Another key regulator of pressure-induced epithelial responses is the mechanosensitive Ca²⁺ channel PIEZO1, which detects cell elongation, increases Ca²⁺ influx, and regulates cell proliferation and apoptosis. However, studying these processes in vitro remains challenging, limiting the development of targeted therapies for post-ERCP and gallstone-induced pancreatitis.

Aims & Methods

To overcome these limitations, we aimed to utilize apical-out pancreatic organoids (hPOCs) to model pressure-related disease mechanisms ex vivo.
To investigate this we generated hPOCs from pancreatic tissue of three cadaver donors. Polarity switching was induced by Matrigel removal. Conventional and apical-out hPOCs were analyzed by RNA sequencing and live-cell fluorescent imaging. Gene expression changes in response to 1 µM PIEZO1 activator (YODA1) were assessed by qRT-PCR.

Results

Polarity switching led to reduced PIEZO1 expression and decreased intraluminal pressure, resulting in downregulation of cytoskeletal and cell cycle-related genes (ACTB, VCL, LPXN, LMNA, cyclins) as well as pro-inflammatory cytokines (CXCL1-3, CXCL8).
Heatmap analysis of transcriptomic data revealed distinct gene expression patterns between apical-in and apical-out organoids. Apical-in organoids exhibited upregulation of cell cycle and cytoskeletal genes, suggesting increased proliferation, while apical-out organoids showed a quiescent phenotype with reduced proliferative activity.
Gene Ontology (GO) analysis confirmed that apical-in organoids were enriched in pathways related to chromosome segregation, mitotic progression, and microtubule organization, whereas apical-out organoids had lower expression of these genes.
Volcano plot analysis of differentially expressed genes identified significant upregulation of MKI67, CENPF, ASPM, and UHRF1 in apical-in organoids, indicative of a proliferation-driven state. Conversely, apical-out organoids showed enrichment in DUOXA2, NUPR1, VNN2, and GBP2, genes associated with oxidative stress and inflammatory response, supporting the hypothesis that apical-in organoids reflect a pressure-induced, inflammation-like state.
Furthermore, polarity switching resulted in enhanced Cl⁻ efflux via CFTR and ANO1, likely due to the absence of sustained intraluminal pressure. Pharmacological activation of PIEZO1 by YODA1 reversed the downregulation of pro-inflammatory cytokines in apical-out hPOCs, suggesting that PIEZO1 mediates the inflammatory phenotype observed in conventional organoids.

Conclusion

Our results suggest that conventional apical-in pancreatic organoids mimic a pressure-induced inflammatory state, driven by PIEZO1-dependent signaling. In contrast, apical-out organoids, which lack sustained luminal pressure, provide a more physiological model for studying epithelial homeostasis. This platform offers new opportunities for investigating pressure-induced pancreatitis and developing targeted therapeutic strategies.

Introduction

The Revision of the Atlanta Classification (RAC) defines severe acute pancreatitis (AP) by the presence of persistent organ failure (OF), limited to respiratory, renal, or cardiovascular systems, this being associated with a high mortality rate. Whether gastrointestinal bleeding (GIB) and impaired mental status (IMS) should be considered as OF remains unclear. We aimed to assess the association of GIB and IMS with mortality and other outcomes.

Aims & Methods

We performed a retrospective analysis of a prospective database including 1,612 AP patients. GIB was defined as bleeding >500 mL. IMS was defined as a Glasgow score ≤14 at baseline. Multivariate logistic regression models were used to assess associations with mortality, controlling for comorbidity and RAC- defined OF. Two models were used: one including all OF (any duration), and another including only persistent OF.

Results

GIB occurred in 1.5% and IMS in 3% of patients. Both were associated with worse outcomes in bivariate analysis. In multivariate models, GIB was not independently associated with mortality. IMS was independently associated with mortality (aOR 4.0, 95% CI 1.2–13.4) only when adjusting for persistent OF, but not when adjusting for OF of any duration. Renal, respiratory or cardiovascular OF of any duration, as well as persistent OF, had an independent and very strong association with all the outcome variables including mortality, clearly differentiating them from GIB and IMS.

Conclusion

GIB and IMS are markers of disease severity but do not show a consistent independent association with mortality comparable to the current RAC definition of OF.

Introduction

Acute Pancreatitis (AP) is a common gastrointestinal disease with an incidence of 34 per 100,000 and mortality of up to 30% in its severe form. Frequently, AP is complicated locally and systemically. Splanchnic Venous Thrombosis (SVT) is a well-known local vascular complication of AP involving the portal vein (PV), the splenic vein (SV), and the superior mesenteric vein (SMV) in combination or alone.

Aims & Methods

The aim is to study and analyze pancreatitis-related SVT patients' epidemiological data and characteristics at the Institute of Pancreatic Diseases, Semmelweis University.From the Institute of Pancreatic Diseases, out of a total of 1141 patients hospitalized with AP between 1st January 2022 and 21st February 2024, we found 45 patients' data with pancreatitis-related thrombosis using the international code for diseases. We extracted the individual data of 45 patients from E-Med Solution and EESZT and further analyzed it. 19 patients were excluded based on inclusion and exclusion criteria.

Results

From the total of 1,141 patients, 26 were with pancreatitis-related SVT. Among these, 19 (73%) were male and 7 (27%) were female. Regarding the severity, 19 patients experienced moderate acute pancreatitis (AP), while 7 had severe AP. The most common etiologies were alcohol consumption (41%), biliary (14%), and hypertriglyceridemia (14%). The average age of the patient population was 48.3 years (SD 13.5), with male patients averaging 44.7 years (SD 10.2) and female patients averaging 58 years (SD 16.2). The average length of hospitalization was 14.5 days (SD10.4). The average BMI of the patient population was 28.4 kg/m2 (SD 4.8). Of 7 severe AP patients, 6 were males with alcoholic etiology, an average BMI of 28.9 kg/m2 (SD 3.2) and higher on admission mean Procalcitonin of 1.1 ng/mL(SD 1.23) (Vs 0.81ng/mL (SD 2.08)).
The splenic vein (SpV) was the most affected vessel, involved in 11 patients (42%), followed by superior mesenteric vein (SMV) in 3 patients (11%) and portal vein (PV) in 2 patients (7%) and 10 patients (38%) with two or more vessels involved of SpV, SMV, and PV. Of the 26 patients, 17 (65%) showed recanalization after receiving LMWH (57%) and DOAC (68%) therapy after discharge. The splenic vein recanalized the highest (68%) among the vessels.

Conclusion

In our analysis, splenic vein is the most involved vessel among the splanchnic veins and also the vessel with highest recanalization after anticoagulant therapy. Our data clearly shows anticoagulant therapy has a better outcome in patients with acute pancreatitis-related SVT. Therefore, dynamic changes of SVT should be closely monitored, and antithrombotic therapy should be rapidly initiated to prevent the further extension of thrombosis and subsequent complications. Unfortunately, major guidelines on the management of AP are silent on this aspect.Hence further studies are necessary to improve the standard of care for the AP patients with SVT.

Introduction

Alcohol is a common cause of acute pancreatitis, and ongoing consumption increases the risk of recurrent episodes. There are no international guidelines to direct behavioural or pharmacological interventions to reduce recurrence of alcohol-associated acute pancreatitis (AAP). Studies exploring the role of addiction medicine in patients with AAP are limited.

Aims & Methods

This study describes the uptake and role of the Addiction Medicine Unit (AMU), a specialist consultative service, in patients admitted with AAP. We conducted a retrospective cohort study including all inpatients diagnosed with AAP at a large multisite tertiary health service in Melbourne, Australia between May 2022 to May 2024. Patient demographics, diagnosis of alcohol use disorder (AUD) and pharmacological and non-pharmacological interventions provided by the AMU were obtained from the patient’s medical records.

Results

A total of 231 patients with 314 admissions with AAP were identified. Most were males (77.9%) with a median age of 44 years (IQR 21), with median bedside index of severity in acute pancreatitis (BISAP) score of 1 (IQR 1). Of the patients, 35 (11.1%) had necrotising pancreatitis, 30 (9.6%) required admission to the intensive care unit (ICU), and 1 patient died from AAP. The prevalence of AUD was 82.3%. Referral to the AMU occurred in 56.7% of admissions, predominantly among those with AUD (87.6%). Patients referred to the AMU had a higher median number of standard drinks per week (70 standards, range 6-385 standards) compared to those who were not referred (49 standards, range 1-301 standards) (p=0.024). The AMU recommended outpatient services alone in 40.4%, both pharmacological and outpatient interventions in 37.6%, and medications alone in 21.9%. Outpatient services included either a service for community-based assessment and counselling (86.4%), residential rehabilitation programs and/or detox services (5.8%), follow up in the AMU outpatient clinic (3.9%) or a combination of these outpatient services (3.9%). There were 137 (43.6%) admissions in which patients were commenced on medications for AUD. Topiramate (42.6%), and naltrexone (42.6%) were the most prescribed pharmacological agents by the AMU, followed by baclofen (9.8%), acamprosate (4.1%) and disulfiram (0.8%). Over the 2-year period, 54 (23.4%) were readmitted with AAP. Most patients were not readmitted within 30 days of discharge (73.2%) however there were 33 (10.5%) patients readmitted for pancreatitis or pancreatitis-related complications including pain or infection, and 18 (5.7%) readmitted to hospital for non-pancreatitis related reasons. Patients who were older (median 49 years) were more likely to be readmitted with AAP compared to those who were younger (median age 43 years) across the study period (p=0.05). There were six patients re-admitted with AAP with their index admission deemed related to an alcoholic binge without suspected underlying AUD. Of these six patients, only two were referred and reviewed by the AMU, with the other four patients not referred.

Conclusion

Our study highlights the critical role of the AMU in managing AAP, particularly given the high prevalence of concurrent AUD in this population. Despite this, significant gaps remain in screening for AUD and initiating referrals, resulting in only half of AAP patients being referred. Considering the substantial morbidity and healthcare cost associated with alcohol, efforts to improve referral practices during index admissions may be key to reduce readmissions for AAP and improve patient outcomes.