Introduction

Differential diagnosis of solid pancreatic tumours (SPT) is a clinical challenge. Development of advanced imaging techniques associated with EUS, such as elastography and contrast enhancement, has been a step forward in this context. EUS-guided detective flow imaging (DFI) is a very recent technology allowing the evaluation of microvascularization and low-velocity blood flow without the need of contrast agents.

Aims & Methods

Aim of our study was to evaluate the findings obtained by EUS-DFI in SPT and compare them with contrast enhanced harmonic EUS (CEH-EUS).
Methods: A prospective, single-centre, observational study in patients who underwent EUS for the evaluation of SPT was designed. Procedures were performed with a linear echoendoscope (Fujifilm 740UT) attached to the ultrasound system Arietta 850. Lesions were characterized according to the vascularization pattern (hypervascular, isovascular and hypovascular) described with both methods. Final diagnosis was based on histology after EUS-guided biopsy. Data area shown as mean ± SD and percentage.

Results

44 patients were included (mean age 67 years, range 24-88, 23 males). Mean tumour size was 26.1 ± 15.7 mm. Fourteen (31.8%) lesions were located in the head of the pancreas, 19 (43.2%) in the body, 9 (20.5%) in the tail and 2 (4.5%) in the uncinate process. Final diagnosis was adenocarcinoma in 24 patients (54.5%), neuroendocrine tumour in 13 (29.5%), inflammatory mass in 3 (6.8%), autoimmune pancreatitis in 1 (2.3%), pancreatic necrosis in 1 (2.3%), accessory spleen in 1 (2.3%) and lipoma in 1 (2.3%). Agreement regarding the vascular pattern of SPT between CEH-EUS and EUS-DFI was reached in 97.7% of the cases. All adenocarcinomas were hypovascular, inflammatory masses and autoimmune pancreatitis isovascular, pancreatic necrosis avascular, and accessory spleen and lipoma hypervascular at both CEH-EUS and EUS-DFI. All 13 neuroendocrine tumours were hypervascular at CEH-EUS, 12 of them (90%) at EUS-DFI.

Conclusion

EUS-DFI allows evaluating the microvascular pattern of SPT with a similar accuracy than CEH-EUS, but without the need of using contrast agents.

Disclosure

Julio Iglesias-Garcia. Advisor Pentax, FujiFilm, Mediglobe

Clinical Case Summary

The authors present a case of a 22-year-old male with no previous medical history, apart from COVID-19 in January 2022, which had a mild course. He was referred to a medical appointment in our department after routine blood tests, from March 2022, that revealed abnormal liver biochemistry elevation (ALT 476U/L, AST 139U/L, GGT 135U/L, normal ALP and total bilirubin), which was normal in the previous year. He reported no symptoms and physical examination was unremarkable. There was no chronic medication, recent introduction of drugs, herbal products or epidemiology for zoonoses.
Abdominal ultrasound and CT scan with IV contrast showed discrete hepatomegaly with homogeneous steatosis, without focal lesions, and splenomegaly.
An extensive work-up excluded hepatotropic agents, metabolic causes, autoimmune aetiologies and haematological or lymphoproliferative disorders. The serum protein electrophoresis and immunofixation, immunoglobulins count, tumour markers and celiac disease serology were also normal. During this period, the patient maintained the same liver elevation pattern with stable values, without any alteration in total bilirubin, albumin, coagulation and hemogram, except for the appearance of discrete thrombocytopenia. We remained asymptomatic, with no signs of hepatic decompensation or haemorrhagic diathesis.
The percutaneous liver biopsy documented septal fibrosis and regenerative nodules, interface hepatitis, focal hepatocellular necrosis and, notably, the presence of numerous multinucleated giant hepatocytes, allowing the diagnosis of post-infantile giant cell hepatitis (PIGCH), in cirrhotic phase.
We present a case of PIGCH, with rapid progression to cirrhosis, whose aetiology remains unknow. Viral aetiologies account for 20% of the cases. Given the temporal association between SARS-CoV-2 infection and liver enzymes’ elevation, we cannot exclude this agent as a possible culprit. To our knowledge, this is the first case reporting this possible trigger.

References

Xiao, Y., Gao, Z. H., & Deschenes, M. (2021). Autoimmune post-infantile giant cell hepatitis: a case report and review of the literature. Canadian liver journal, 4(2), 104–109. https://doi.org/10.3138/canlivj-2020-0024;
Jiao, J., & Zhang, X. (2022). Post-infantile Giant Cell Hepatitis: A Literature Review and Meta-analysis. Journal of clinical and translational pathology, 2(3), 100–107. https://doi.org/10.14218/jctp.2022.00016.

Clinical Case Summary

A 40-year-old male came to our emergency department referring worsening jaundice, mental status deterioration, epigastric pain and anorexia over the past week. Four weeks earlier he presented odynophagia, myalgias, and hand pruritus but didn’t seek medical attention.
Patient’s clinical background included cognitive impairment due to peripartum anoxia and type 2 Diabetes Mellitus. At admission, he had elevated liver enzymes (R value=2,7), coagulopathy (INR 1.3), pancreatic enzymes >3 times the upper normal level and hyperbilirubinemia (mostly conjugated).
The CT-scan revealed pancreatic tail globosity, diffuse abdominal and retroperitoneal peri-centimetric lymph nodes and excluded biliary lithiasis.
After common causes of acute hepatitis and pancreatitis were ruled out, and since patient was at risk of acute liver failure despite supportive treatment, a liver biopsy was performed. Autoimmune hepatitis, drug-induced liver injury or lymphoproliferative disease were held as potential differentials. Hepatitis E Virus (HEV) RNA was then found and genotyped in the serum (genotype 3). HEV infection was assumed as the cause for both hepatitis and pancreatitis. Histological pattern was inconclusive and epidemiological source wasn’t found.

HEV infection paradigm has changed and is now considered an endemic zoonotic infection in most high-income countries (Portuguese seroprevalence is 16.3%)¹. Infection occurs due to ingestion of undercooked pig or boar meat and should be suspected in every acute hepatitis, mostly with a cholestatic pattern.
The setting of acute HEV hepatitis complicated with acute pancreatitis (AP) is uncommon². AP usually starts after a median of 10 days of jaundice onset³. Literature only reports association between AP and HEV caused by genotype 1 from Southeast Asia^{3 4}, and genotype 3 was only related to gallstone-related pancreatitis, according to current knowledge⁵. This might be the first form of HEV genotype 3 infection with hepatitis and pancreatitis.

References

1. Nascimento MSJ, Pereira SS, Teixeira J, et al. A nationwide serosurvey of hepatitis E virus antibodies in the general population of Portugal. Eur J Public Health 2018;28(4):720-24. doi: 10.1093/eurpub/ckx213 [published Online First: 2017/12/14]
2. Debnath P, Datta AK, Chakraborty U, et al. Acute viral hepatitis E complicated with acute pancreatitis in an immunocompetent adult. BMJ Case Rep 2021;14(2) doi: 10.1136/bcr-2020-239684 [published Online First: 2021/02/06]
3. Haffar S, Bazerbachi F, Garg S, et al. Frequency and prognosis of acute pancreatitis associated with acute hepatitis E: A systematic review. Pancreatology 2015;15(4):321-6. doi: 10.1016/j.pan.2015.05.460 [published Online First: 2015/06/08]
4. European Association for the Study of the Liver. Electronic address eee, European Association for the Study of the L. EASL Clinical Practice Guidelines on hepatitis E virus infection. J Hepatol 2018;68(6):1256-71. doi: 10.1016/j.jhep.2018.03.005 [published Online First: 2018/04/04]
5. Karlsson M, Norder H, Bergstrom M, et al. Hepatitis E virus genotype 3 is associated with gallstone-related disease. Scand J Gastroenterol 2019;54(10):1269-73. doi: 10.1080/00365521.2019.1666163 [published Online First: 20190925]

Introduction

Hypertriglyceridemia is a well-established cause of acute pancreatitis, representing up to 35% of all etiologies. The risk of developing acute pancreatitis increases progressively with serum triglyceride (TG) levels over 500 mg/dL. The degree of TG elevation is also associated to the severity of hypertriglyceridemia-induced pancreatitis (HTGP). Besides general measures, it has been suggested from observation studies that, in selected patients, insulin and plasmapheresis may have a role in the management of this condition.

Aims & Methods

We present an observational retrospective study of patients diagnosed with severe HTGP treated with plasmapheresis (PX) in an Intensive Care Unit (ICU) between January 2013 and March 2023.

Results

Of the 19 patients included in this study, 89% were men (n=17) and the mean age of presentation was 41 ± 7 years. Around 90% of patients were obese with a mean body mass index (BMI) of 29 ± 3 kg/m². The average APACHE II score was 9±7 and most patients did not require organ support (n=16, 84%). All the selected patients had severe hypertriglyceridemia at admission (1225 to 4700 mg/dL) and underwent PX within 48h of ICU admission. Levels of TG were measured before and after each plasmapheresis. 68% of patients needed only one treatment to reduce TG to a value below 500 mg/dL (n=13), 26% needed two treatments (n=5) and 5% needed four (n=1). A total of 27 PX were conducted. The average decrease in TG levels per treatment was 67% and 74% with the first treatment. The mean volume exchanged was 3683 mL ± 859 mL, and the most used replacement solutions were albumin/crystalloid (n=12, 44%) and albumin alone (n=11, 41%). The technique was interrupted mainly due to elevated transmembrane pressure (n=11, 40%). There were no PX interruptions due to complications related to the patient. Although heparin was used in all patients for anticoagulation, no hemorrhagic complications were associated to the technique. Hypotension occurred in 7% of plasmapheresis and was solved with crystalloid administration . The mean ICU length of stay was 7+11 days and the mean hospital length of stay was 17+21 days. The hospital mortality was 5% (n=1).

Conclusion

PX proved to be successful in lowering TG levels in HTGP. One to two plasma exchanges effectively reduced the serum TG level. There was a low rate of procedure-related complications. However, having no comparison with standard treatments, the impact of this technique on the patients’ clinical outcomes is still uncertain. Further prospective randomized clinical studies are needed to outline an efficient treatment for the management of HTGP.

References

Padmanabhan, A et al, “Guidelines on the Use of Therapeutic Apheresis in Clinical Practice”, J Clin Apher. 2019;34:171–354.
Banks PA, “Practice guidelines in acute pancreatitis.”, Am J Gastroenterol. 2006;101(10):2379)
Rawla, P. “Hypertriglyceridemia-induced pancreatitis: updated review of current treatment and preventive strategies”, Clin J Gastroenterol. 2018 Dec;11(6):441-448.
Faria, R. et al, “Therapeutic Plasmapheresis: Seven Year Experience of an Intensive Care Unit in Portugal”, Acta Med Port 2022 Mar;35(3):176-183
Stefanutti, C. et al, “Severe Hypertriglyceridemia-Related Acute Pancreatitis”, Therapeutic Apheresis and Dialysis 2013; 17(2):130–137

Introduction

Gastric injury induces metaplasia is based on parietal cells loss and reprogramming chief cells into proliferative, mucin-rich spasmolytic polypeptide-expressing metaplasia (SPEM) cells. Previously, we demonstrated that parietal cell-selective Slc26a9 deficiency in mice promotes the development of SPEM and progress to gastric intraepithelial neoplasia in mice (Liu et al., Cellular oncology; 2022; Deng et al., DDW2023). However, the exact role of Slc26a9 in injury-induced metaplasia is need further investigated.

Aims & Methods

We used immunostaining to characterize the expression pattern of Slc26a9 during murine gastric development, homeostasis, and injury in homeostasis, after conditionial genetic deletion of Slc26a9. Furthermore, to reveal the functional role of Slc26a9, Injury-induced metaplasia was established in Slc26a9^fl/fl mice and Slc26a9^fl/fl/Atp4b-Cre mice with high-dose tamoxifen.

Results

Mice with parietal cell selective Slc26a9 deficiency first developed spontaneous parietal cell damage, which subsequently led to SPEM. Parietal cell injury was associated with the release of typical pyroptosis factors, including NRLP3, Caspase-1, ASC, GasderminD, IL-1β and IL-18. At the same time, SLC26A9 colocalized with caspase1, NLRP3, GSDMD, and NLRP3 and GSDMD, and produced a large number of reactive oxygen species (ROS), markers of mitochondrial damage, thereby expanding membrane perforation of GSDMD-N fragments and amplifying inflammasome-mediated parietic cell pyrodeath. At the same time, electron microscopy showed that after the knockout of the Slc26a9 gene, the mitochondria of the murine wall cells were obviously swollen, the cell membrane structure was blurred and damaged, the matrix was more dissolved, the ridge was broken and disappeared, and there were many bubble protrusions. This suggests that parietal cell specific SLC26A9 gene deletion may lead to parietal cell scorch death through mitochondrial damage mediated by GSDMD. However, with a large number of parietal cell damage and loss, gastric hypergastrinemia stimulates Tuft cell proliferation and migration to the gastric mucosa for colonization, and secretes a series of alarm hormones such as IL-25, IL-33, HMGB1. Moreover, ILC2 cell secretory factors such as IL-17RA and IL-17RB, GATA3, CD90, CD25 were up-regulated. M2 macrophage polarization-related markers such as Arg1, Fizz1, Ym1, Klf4 and secreted chemokines such as CCL24 and CCL22 were significantly up-regulated. The immunofluorescence staining of F4/80+ and CD163+ was significantly increased. This suggests that the spontaneous injury of parietal cells caused by the deletion of SLC26A9 gene in gastric parietal cells may lead to gastric dysfunction (hypoacid and hypergastrinemia) and mucosal epithelial injury, which may promote the occurrence of SPEM through IL-25 mediating the activation of ILC2 cells to regulate the cellular immune mechanism of macrophage M2 polarization.

Conclusion

Slc26a9 target deletion in parietal cells leads to spontaneous damage and scorch death of parietal cells, which is the core target and cell origin of initiating SPEM. After parietal cell specific Slc26a9 gene deletion leads to spontaneous injury of parietal cells, gastric dysfunction and mucosal injury result in the release of alarm hormone IL-25, which promotes the development of SPEM by activating IL-25-ILC2-macrophage M2 polarization axis. Slc26a9 plays an important protective role in stabilizing gastric epithelial cell differentiation and gastric mucosal immune homeostasis.

Disclosure

No conflict of interest

Introduction

The Epi-IBD cohort is a prospective European population-based cohort of 1,390 patients diagnosed with inflammatory bowel disease (IBD) in 2010 and 2011 according to Copenhagen criteria. Of these, 482 were diagnosed with Crohn’s Disease (CD), 817 with ulcerative colitis (UC) and 91 with IBD unclassified (IBDU). The Epi-IBD cohort was established to examine differences in incidence, treatment strategies, disease course and prognosis among IBD patients in Eastern and Western Europe.

Aims & Methods

This study aims to describe the use of biological therapy as well as the treatment prior to biological therapy. IBD patients were followed prospectively from the time of diagnosis until the 31^st December 2020, death, emigration or loss of follow-up. Clinical data on surgery, hospitalizations, and medical treatment, were captured throughout the follow-up period and entered into a validated web-database, www.epi-ibd.org.

Results

During a median follow-up period of 10.7 (interquartile range (IQR), 10.0-11.4) years, 34% (N=165/482) of CD and 15% (N=122/817) of UC patients were started on biological therapy. Biological therapy was initiated within the first year after diagnosis in 16.8% (N=81/482) of all CD and 3.8% (N=31/817) of all UC patients. In median biological therapy was started at 1.0 year (IQR, 0.3-3.1) and 2.7 years (IQR, 1.6-4.0) after CD and UC diagnosis, respectively. First-line biological therapy was infliximab in 74% (N=213/287) and adalimumab in 22% (N=64/287) of the patients. The remaing (N=10/287) received either Golimumab, Vedolizumab, Ustekinumab or were part of a trial/unknown. The sequences of biological therapies are displayed in Sankey diagrams, Figures 1 and 2. Herein illustrated is that 34% (N=56/165) CD and 34% (N=41/122) UC received at least two different biological drugs. Immunomodulators were initiated simultaneously to the first biological therapy in 19% (N=31/165) of CD patients and in 9% (N=11/122) of UC patients. Overall 63% (N=104/165) CD and 51% (N=62/122) UC patients were receiving concomittant immunomodulators with the first biological therapy.
The sequences of therapy leading up to biological therapy are displayed in Sankey diagrams, Figures 3 and 4. Herein illustrated is that the most common sequence of treatment before the first biological therapy for CD was 1) Steroids, 2) Immunomodulators (21%, N=34/165), and for UC was 1) 5-aminosalicylic-acid (5ASA), 2) Steroids, 3) Immunomodulators (39%, N=48/122). Prior to the first biological therapy one, two and three or more courses of systemic steroid were used in 41%, 28% and 17% (N=67, 47 and 28) of CD patients and 43%, 24% and 26% (N=52, 29 and 32) of UC patients. In 14% (N=23/165) and 7% (N=9/122) of CD and UC patients, systemic steroids were not used prior to first biological therapy. In patients having immunomodulators prior to biological therapy, these were administered for a median of 0.5 (IQR, 0.1-1.9) years and 1.1 (IQR, 0.2-3,2) years in CD and UC, respectively. For 5ASA this was 0.8 (IQR, 0.2-1.5) years for CD and 2.2 (IQR, 0.8-4.3) years for UC.

Conclusion

In this multicenter European population-based cohort, different prescribing patterns for biologics emerge: 34% of CD and 15% of UC patients received biologics within 10 years after diagnosis. Infliximab was the most common first-line biological therapy. Only about half of the patients received concomitant immunomodulators. Prior to the first biological therapy, most patients were exposed to systemic steroids and many to repeated courses.