Introduction

Buried bumper syndrome (BBS) is a complication of a percutaneous endoscopic gastrostomy (PEG) which occurs when the internal bumper migrates into the gastric wall. There are several techniques used to manage BBS. The Flamingo is a novel device specifically developed to release buried bumpers and was first used at North Bristol Trust (NBT) in 2018. This study compared the effectiveness of methods used to free buried bumpers before and after the introduction of this device.

Aims & Methods

The primary endpoint was to determine the success of the Flamingo device in resolving BBS compared to balloon dilatation, needle knife and surgical removal. Data was obtained retrospectively from single endoscopy unit study between January 2010 to July 2023. Due to low numbers, balloon dilatation and needle knife were grouped together for analysis. Additional outcome parameters were complication rate, site change and sedation. Baseline patient demographic and clinical parameters were compared between groups.

Results

Forty-three cases of BBS were identified where balloon/knife, Flamingo or surgery was used to free the buried bumper (median age, 59; 31 males (72.15%)). 20 BBS cases attended endoscopy prior to January 2018 with balloon/knife intervention successful in 11/16 patients (68.75%) and 4 successful surgical removals. After January 2018, balloon/knife interventions succeeded in 2/5 (40%), with subsequent successful surgical (n=1) or flamingo (n=2) interventions. Flamingo alone succeeded in 17/18 patients (94.4%). Combining all BBS cases, the overall success rate of Flamingo was 95% compared to 61.9% for balloon/knife (P = .02). Surgical removal success rate was 100%. Complication rate was highest post-surgical removal (60%) compared to Flamingo (20%) and balloon/knife (4.76%).

Conclusion

Removal of buried bumpers using the Flamingo device was significantly more successful than using the balloon/knife. All surgical procedures were prior to Flamingo or required to rescue balloon/knife. This means there needs to be investigations to determine whether the flamingo can obviate need for surgery and whether these two procedures cause an overall excess of complications.

Disclosure

No Conflict of Interest

Introduction

Potential celiac disease (PCD) is a clinical condition characterized by the presence of a positive CD-specific serology and a normal intestinal architecture. Asymptomatic PCD patients are generally addressed to continue on a gluten containing diet (GCD), but long-term risks of this approach have never been explored.

Aims & Methods

In the present study we aim at investigating nutritional and autoimmune complications possibly developing overtime in a cohort of asymptomatic PCD children left on a GCD. We compared parameters of growth, nutritional status, and autoimmunity between time of diagnosis and in occasion of last medical check, after a long-term gluten containing diet.

Results

Altogether we collected data from 171 PCD children with a mean follow-up time of 3 years (range 0.35-15.3 years). During follow-up, despite patients did not reduce the amount of daily gluten intake , anti-tissue transglutaminase (anti-TG2) antibodies spontaneously and significantly decreased. Most of parameters analysed did not change over follow-up (height centile, ferritin, albumin., cholesterol, calcium, alkaline phosphatase , parathormone, vitamin D, p>0.05) or even improved (weight and BMI centile, haemoglobin, blood iron, HDL, glycaemia and HbA1C, p<0.05), always remaining in the limit of normality. Equally autoantibodies for other concomitant autoimmune disorders did not increase overtime. Similar results were obtained excluding from the analysis patients that stopped producing anti-TG2 and those with a follow up < 3 years.

Conclusion

Our pilot study provides reassuring results on the maintenance of a gluten containing diet in asymptomatic PCD children, even when a long term follow-up is considered.

Disclosure

no conflict of interest to declare

Introduction

Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease with the lowest 5-year survival rate of all cancers due to late diagnosis and lack of effective treatment. One of the challenges of developing molecular diagnosis and molecular targeted therapy for PDAC is the “mismatch” between research models and patients.

Aims & Methods

This study aimed i) to identify common proteins among different research models and patients and accordingly ii) to identify potential hub proteins and signaling pathways involved in the PDAC pathogenesis by using proteomics-based system modeling of multimodal datasets derived from multiple research models and patients. Mouse PDAC cells (derived from a genetically engineered mouse model with KrasG12D/Pdx1-Cre), PDAC orthotopically tumors in C57B/L6 mice (n=5), mouse PDAC spheroids, mouse pancreatic organoids, mouse PDAC organoids, normal mouse pancreatic tissues (n=5), human PDAC tumor tissue samples from treatment-naїve (n=20), neoadjuvant chemotherapy (n=22), and human PDAC organoids were included. Mass spectrometry-based proteomics, Rstudio, Cytoscape 3.10 and pathway enrichment analysis (using ingenuity pathways analysis, including human PDAC transcriptomic in addition) were used.

Results

In the comparison of PDAC models and patients, shared proteins were identified as follows: 60% between the mouse PDAC cells and the mouse PDAC spheroids, 78% between the mouse PDAC cells and the mouse PDAC tissue, 56% between the mouse PDAC spheroids and the mouse PDAC tissue, 66% between the mouse PDAC cells and the mouse PDAC organoids, 54% between the mouse PDAC spheroids and the mouse PDAC organoids, 38% between the mouse PDAC and the human PDAC tissues, 31% between the human PDAC tumor and the human PDAC organoids, and 60% between the mouse and the human PDAC organoids. A total of 1,367 common proteins were identified within all the PDAC models. Among these proteins ACTB, HSP90AA1, HSPA8, HSP90AB1, HSPA4, EEF2, RPS3, RPS20 and GAPDH were the top 10 hub proteins (with >300 node connections). Upon comparison of all eight models, eight proteins were identified as unique to PDAC, namely FAHD1, ARSA, NEK9, SERPINB9, LAMTOR2, SNRPG, TMED3, and RAB1A. There was a correlation in terms of z-score regarding signaling pathways between the mouse PDAC and human PDAC (p<0.001), particularly in activations of nerve growth factor signaling, integrin signaling, and neuregulin signaling. Central hub proteins commonly found in the mouse models included vinculin (membrane-cytoskeletal protein) as one of the high connectivity nodes and β-catenin and probable ubiquitin carboxyl-terminal hydrolase FAF-X (involved in axonal growth and neuronal cell migration) as high centrality nodes. In patients, central hub proteins that were dysregulated after chemotherapy included 14-3-3 protein zeta/delta (encoded by YWHAZ gene), β-catenin and SRC. Among the 47 proteins that were associated with altered metabolism after the chemotherapy in patients, CD44, CTNND1, APOA 1, PARVA, and SCRBS1 were nodes with low degrees, and desmosomes (DSP, KP3, PPL), PRTN3, thrombospondin-2 (THBS2), and DMBT1 were the most down-regulated proteins without nodes, and APOA1, caveolin-1 (encoded by CAV1), LRP1 were the most up-regulated proteins with nodes.

Conclusion

The system modeling identified the common proteins among the research models and patients and the hub proteins and signaling pathways, suggesting the potential translational targets of PDAC.

Introduction

Aims & Methods

This retrospective cohort study encompasses all elective NRLAR, RLAR, and APR procedures performed for non-metastatic primary rectal carcinoma across 11 Dutch centers between 2013 and 2020. The primary outcome measured was 3-year disease-free survival (DFS), while secondary outcomes included 3-year overall survival (OS) and local recurrence (LR). Data analysis employed Kaplan-Meier survival analysis, and results were juxtaposed using log-rank testing. The association between resection type (NRLAR, RLAR, and APR) was further explored using multivariate Cox regression analysis.

Results

Conclusion

Disclosure

Introduction

Ascites of any etiology presents a major problem in patients with malignant biliary obstruction (MBO) and failed ERCP, where trans-mural drainage is indicated, but presumed to be unsafe due to the risk of bile leak. We planned to evaluate the safety of Endoscopic Ultrasound-guided choledocho-duodenostomy (EUS-CDS) in our patients with ascites.

Aims & Methods

We palnned to evaluate the safety of endoscopic ultrasound-guided choledocho-duodenostomy (EUS-CDS) in malignant biliary obstruction (MBO) and ascites in a retrospective study. Prospectively maintained records of consecutive patients with MBO, with or without ascites, and undergoing EUS-CDS for biliary drainage, were retrospectively analysed. Technical success was defined as successful stent deployment, while clinical success was defined as biliary decompression (biochemical and radiological), and relief in cholangitis. Complications such as bile leak, fever and abdominal pain were recorded, and the data were compared between patients with and without ascites.

Results

Between November 2019 and March 2024, 60 patients underwent EUS-CDS for MBO. Of these, 38 (65%) were males and the mean age was 61.49 years. At the time of the procedure, 18 patients had ascites (30%) had ascites, of which 11 had Grade II and 7 had Grade III ascites. The most common malignancies wer pancreatic cancer (28), peri-ampullary carcinoma (12) and distal cholangiocarcinoma (9). Other lesions seen were duodenal cancer (5), malignant lymph node metastases causing MBO (4) and gall bladder cancer (2). Technical success was achieved in 100% procedures, and clinical success was also achieved in all the patients. In the group with ascites, 3 patients had bile leak, which was managed conervatively with percutaneous trans-hepatic biliary drainage (PTBD). One patint had fever resposnsive to antibiotics; the other two had mild abdominal pain responding to analgesics. In the group with without ascites, two patients had bile leak, one had mild pain, and the other two had self-limited fever.

Conclusion

EUS-guided drainage is generally presumed to be contra-indicated in the presence of ascites [1]. EUS-hepatico-gastrostomy has been shown to be safe in the presence of ascites [2]. Our study shows that EUS-CDS is safe & effective in MBO with ascites. Further, larger studies are needed to evaluate its long-term safety and the effect on the survival and quality of life of the patients.

References

1. Sundaram S, Dhir V. EUS-guided biliary drainage for malignant hilar biliary obstruction: A concise review. Endosc Ultrasound. 2021 May-Jun;10(3):154-160. doi: 10.4103/EUS-D-21-00004.
2. 1.Yasuda T, Hara K, Mizuno N et al. Safety of endoscopic ultrasound-guided hepatico-gastrostomy in patients with malignant biliary obstruction and ascites. Clin Endosc. 2023 Sep 7. doi: 10.5946/ce.2023.075

Introduction

An increased risk of pancreatic cancer has been reported in families with breast cancer history carrying BRCA1 and BRCA2 mutations. Pancreatic cancer is associated with familial and hereditary cancer syndromes. Multigene panel testing for pancreatic cancer detected germline variants BRCA1/2, PALB2, ATM, TP53, MLH1, STK11/LKB1, APC, CDKN2A, and SPINK1/PRSS1 as high-risk genes. Active pancreatic surveillance using computed tomography (CT), magnetic resonance imaging (MRI), and echoendoscopic (EE) are recommended for high-risk individuals who have a family history of pancreatic cancer or harbor these pathogenic germline variants to improve the detection rate and the prognosis of pancreatic cancer. We evaluated the performance characteristics of echoendoscopically guided fine needle biopsy (EE-FNB) in this subset of patients.

Aims & Methods

This is a retrospective analysis of a prospective database total of 99 families with ≥1 case of breast cancer tested for mutations in BRCA1 and/or BRCA2. The eligible patients were the ones that underwent EE-FNB at a tertiary hospital with an Oncology center due a focal pancreatic lesion observed on CT/MRI, from January 2022 to January 2024. Patients were excluded if (1) they had obstructive jaundice or (2) the lesion appeared cystic on CT/MRI. The main outcome measures were (1) prevalence of the association between BRCA 2 positive and pancreatic cancer (2) performance characteristics of EE-FNB for identification of malignancy.

Results

In the 99 patients in the study, a focal pancreatic lesion was identified with pancreatic adenocarcinoma by EE-FNB. The final diagnosis included 20 patients with breast cancer and BRCA2 positive undergoing oncological treatment or follow-up, with a mean age of 32.8 +/- 2.2 years. EE was performed in an average of 19 +/- 11.3 days. EE-FNB showed an accuracy of 100% for the diagnosis of malignant neoplasia, with a sensitivity of 100%, specificity of 100%.

Conclusion

EE-FNB diagnostic yield was substantial in established high-risk mutation carriers, is highly accurate in patients with focal pancreatic lesion on CT/MRI, without obstructive jaundice. EE-FNB can potentially be used as a definitive diagnostic test in the management of these patients.

Introduction

Thiopurines are vital therapeutic agents for inflammatory bowel diseases but often cause severe myelosuppression. The NUDT15 polymorphism, particularly p.Arg139Cys (NUDT15R139C), is strongly linked to severe leukocytopenia and is prevalent in Asian populations. Despite thiopurine use during pregnancy, it remains unclear if NUDT15R139C affects fetal thiopurine sensitivity.

Aims & Methods

The human and murine NUDT15 proteins share 89% homology with the preservation of arginine at codon 139 of human NUDT15 in codon 138 of murine Nudt15. We established a knock-in mouse model with a point mutation (c.412C>T) generating p.Arg138Cys (Nudt15^R138C), mimicking the human phenotype. In the current study, we investigated offspring generated from Nudt15^+/R138C or Nudt15^+/+ female mice that were mated with Nudt15^+/R138C male mice and simultaneously administered with mercaptopurine (MP).To evaluate the effects of thiopurine on the fetus, we evaluated the number of hematopoietic stem cells in the fetal liver, which is the center of fetal hematopoiesis.

Results

In administration with the tolerable MP dose (0.5 mg/kg) for adult Nudt15^+/R138C mice, genotypes of the genotypes of neonatal mice born from breeding between Nudt15^+/R138 male mice and Nudt15^+/R138 female mice were 35 (37.2%) Nudt15^+/+, 59 (62.8%) Nudt15^+/R138C, and 0 Nudt15 ^R138C/R138C. On embryonic day 14.5, Nudt15^R138C/R138C fetal mice showed shorter body lengths and fewer hematopoietic stem cells in the fetal liver than Nudt15^+/+ fetal mice. The number of fetal HSCs was not altered in any of the Nudt15genotypes without MP treatment. However, it was significantly reduced by MP treatment in Nudt15^+/R138C fetal mice (p< 0.01, mean number 1104 in DMSO and 577 in MP) and in Nudt15^R138C/R138C fetal mice (p< 0.01, mean number 927 in DMSO and 402 in MP), but not in Nudt15^+/+ fetal mice (p= 0.39, mean number 1004 in DMSO and 820 in MP). The number of HSCs in Nudt15^R138C/R138C fetal livers was significantly reduced to less than 50% of that in Nudt15^+/+ fetal livers by MP treatment during gestation (p= 0.0089). In administration with the tolerable MP dose (1.0 mg/kg) for Nudt15^+/+ adult mice, genotypes of neonatal mice born from breeding between Nudt15^+/R138 male mice and Nudt15^{++ /}female mice were 23 Nudt15^+/+ and 0 Nudt15^+/R138C. Without MP administration, neonatal mice were born in a Mendelian fashion.

Conclusion

Fetal toxicity may arise if the fetus has more NUDT15 R139C alleles than the mother, despite safe thiopurine doses for the mother. Analysis of the father's NUDT15 genotype may enable safer thiopurine use during pregnancy, emphasizing the importance of considering parental genotypes in therapeutic decisions.