Introduction

Eosinophilic esophagitis (EoE) is a chronic, food and/or aeroallergen-mediated inflammatory disease , characterized by esophageal dysfunction and eosinophil inflammation of the esophageal mucosa. The incidence of EoE has increased in recent years, including Japan. Pathogenesis of EoE is incomplete, and the data on microbiome related with EoE are limited. The aim of this study was to identify the esophageal and salivary microbiome in patients with EoE.

Aims & Methods

Patients either with EoE or non-EOE patients with symptoms of esophageal dysfunction who underwent esophagogastroduodenoscopy(EGD) at Kawasaki Medical School hospital between April 2021 and April 2023 were enrolled. The endoscopic reference score (EREFS) is used to determine severity of endoscopic findings. EoE patients were classified as the active group, if the presence of esophageal eosinophilia greater than or equal to 15 eosinophils per high-power field were detected during the endoscopy. , Saliva and Esophageal mucous taken from esophagus using brushing samples and saliva were used to investigate microbiome in EoE patients and controls. The microbiota of samples was profiled using the Illumina MiSeq platform.

Results

Total 24 patients were enrolled including8 active EoE patients, 5 inactive EoE patients, and 11 controls.
There were no significant differences in age, PPI use, history of gastroesophageal reflux disease and H. pylori infection among the three groups.The comparative analysis of the taxonomic composition at the genus level among esophageal mucous samples indicated that Streptococcus were less abundant in the active EoE group compared to the other groups, and Stomatobaculum were more abundant in the inactive EoE group than in the controls. On salivary, The abundance of the genera Megasphaera were significantly more prevalent in the inactive EoE group than in the other groups.The abundance of the genera Streptococcus was negatively correlated with ERFFS scores.

Conclusion

Streptococcus might be involved in the pathogenesis of EOE.

Introduction

Diagnosis of chronic pancreatitis (CP) is challenging, especially in early stages when typical clinical signs and parenchymal changes are lacking. To date, evaluation by endoscopic ultrasound (EUS) using Rosemont criteria (RC) is the gold standard for the diagnosis of CP, but represents an invasive method with still suboptimal accuracy. Therefore, it is of crucial interest to develop non invasive, widely applicable tests for the diagnosis of CP. Recently the Gemelli chronic pancreatitis ultrasound score (USCP) has been developed to fill this gap (1). Comparable to liver stiffness measurement, transabdominal ultrasound (US) with 2D shear wave elastography (2D SWE) could represent an additional alternative for the diagnosis of CP. It uses measurement of tissue stiffness, which increases naturally with chronic inflammatory changes, present in CP (2).

Aims & Methods

We conducted a single center prospective case control study where all the included subjects underwent EUS first (for the suspicious of CP or other reasons such as lithiasis), with RC defined patient cohorts with chronic pancreatitis or absence of parenchymal changes. Patients with and without CP subsequently underwent US with evaluation of the pancreas using 2D SWE (in m/s) and characterization by the USCP score (LogiqE10, GE Healthcare). Primary outcome was agreement between the different evaluation techniques, namely RC and 2D SWE. Secondary outcome was the evaluation of a cut off value of SWE differentiating values in CP from normal values. Main exclusion criteria were patients with liver cirrhosis, acute pancreatitis and inability to visualize the pancreas with US.

Results

51 patients with CP and 51 without CP were included. Median SWE were statistically different between groups (no CP 1.50m/s; IQR 1.34-1.63 and with CP 1.83 m/s; IQR 1.68-2.08; p<0.0001). Patients with RC indeterminate for CP had lower SWE values compared to patients with RC consistent with CP (Median 1.67m/s, IQR 1.52-1.72 vs. 1.90 m/s, IQR 1.72-2.12, p<0.0001). Median USCP Score significantly differed between groups (no CP 0-1 points, with CP 3-9 points, p<0.0001). SWE values did not correlate with age, BMI, HbA1c or stool elastase levels, but correlated significantly with USCP score (p<0.001) and RC (p<0.001). USCP Score significantly correlated with BMI (p=0.011), stool elastase levels (p<0.001), HbA1c (p=0.002) as well as RC (p<0.0001). We defined a cutoff- SWE value of <1.42 m/s to rule out CP with a sensitivity of 97% (NPV 98%) and a SWE cut off >1.97 ms/s to diagnose CP with a specificity of 97% (PPV 92%).

Conclusion

Transabdominal ultrasound evaluation of the pancreas with 2D SWE is a promising, widely applicable and non-invasive tool for the diagnosis of CP. More studies with larger cohorts confirming the results are necessary.

References

1)Pagliari D, et al. A new ultrasound score for the assessment and follow-up of chronic pancreatitis: The 'Gemelli USCP score'. Dig Liver Dis. 2020 Jun;52(6):644-650.
2) Yashima Y et al. Acoustic radiation force impulse elastography for noninvasive assessment of chronic pancreatitis. J Gastroenterol. 2012 Apr;47(4):427-32.

Introduction

Recent research has shown that there is considerable interest in studying inflammatory bowel diseases (IBD) due to the potential for dietary interventions to be used as a therapeutic approach for their onset and progression. Evidence suggests that Western-style diets, with high intake of processed foods, food additives, red meat, and animal fat, have been associated with an increased risk of IBD.

Aims & Methods

The purpose of this study is to evaluate the link between an anti-inflammatory exclusion diet and the maintenance of IBD remission, as well as to assess the potential therapeutic advantages of this dietary approach in preserving IBD remission.The inclusion and exclusion criteria were applied to a total of 189 individuals with IBD, with 21 individuals not meeting the criteria. Therefore, 168 eligible patients were enrolled in the study and allocated to either an exclusion diet or a regular diet, based on their personal preference.

Results

A cohort of 84 adult patients with inflammatory bowel disease (IBD) was recruited for the study. The cohort included 47.6% males, with 44 patients having ulcerative colitis (UC) and 40 having Crohn's disease (CD). The intervention group received an exclusion diet consisting of the removal of red and processed meat, fried foods, high-lactose foods, fast food, white bread, sweetened drinks, and vegetable oils rich in omega-6 for a period of 1 year. An equivalent number of IBD patients with similar demographics and disease types formed the control group. The exclusion diet was well tolerated, with 90% of participants adhering to it frequently or always. The study demonstrated that the clinical response was maintained in 80 patients (95.2%) in the intervention group, which was significantly higher than the 72 patients (85.7%) in the control group (p-value=0.036). Although not statistically significant, fecal calprotectin was higher in the control group than in the intervention group at the one-year follow-up interval. Additional information is provided in Table 1.

Conclusion

Patients who adhere to an exclusion diet have the chance of a significantly higher rate of maintenance of clinical remission (95% versus 86% in the control group). A trend toward improvement in inflammation tests was observed in the intervention group, confirming once again that Western-style diet is an important etiological factor in IBD. Therefore, it is recommended that the exclusion, anti-inflammatory diet be presented to all patients diagnosed with IBD as a potential intervention.

Introduction

Pancreatic cancer (PC) is one of the fatal malignant tumors, with a 5-year survival rate is approximately 6%, and is expected to become the second leading cause of cancer deaths by 2030. The poor prognosis of PC is associated with the tumour microenvironment, characterized by excessive fibrosis and extracellular matrix deposition, known as desmoplasia. PC’s highly desmoplastic property not only increases the malignancy of the tumor but also inhibits the penetration and diffusion of anti-cancer drugs, related to drug resistance. Chauhan et al. demonstrated that the angiotensin inhibitor (ASI), losartan reduced stromal collagen and hyaluronan production, thus improving the efficacy of chemotherapy in PC models. Several retrospective studies have reported that the ASI usage group showed higher overall survival (OS) and progression-free survival compared to the non-ASI usage group in PC patients. However, most of the previous studies on ASI in PC patients were based on retrospective data from single institutions. Recently, real-world big data study could explain this subject.

Aims & Methods

In this study, we aimed to conduct whether ASI use in PC patients improve OS using National Health Information Database of the National Health Insurance Service, which represents the entire Korean population. We assessed 209,723 participants for eligibility, diagnosed with pancreatic cancer between 2002 and 2020. A total of 64,219 PC patients were enrolled and divided into 3 groups [chronic ASI users with hypertension (HTN), n=13,239; non-ASI users with HTN, n=5,963; non-HTN group, n=45,017]. We performed propensity score matching to balance the baseline characteristics of the 3 groups and to reduce potential confounders using a logistic regression model with adjustment for the following: age; sex; region of residence (urban or rural); household income; underlying disease of HTN, diabetes mellitus, cardiovascular disease, cerebrovascular disease, chronic kidney disease or chronic pancreatitis; Charlson Comorbidity Index (0, 1 or ≥2); concurrent use of aspirin, metformin, statin; PC surgery type; radiotherapy; and chemotherapy.

Results

Multivariate analysis using Cox regression analysis for matched cohort presented ASI usage, female, younger, history of chronic pancreatitis, CCI ≥2, concurrent use of statin, and receiving distal pancreatectomy were significantly associated with longer OS. In addition, Kaplan-Meier curve for OS of 3 groups according to ASI usage showed that chronic ASI users presented significantly longer OS than non-ASI users and non-HTN group [Hazard ratio, chronic ASI users (control) versus non-ASI users 1.447; chronic ASI users (control) versus non-HTN group 1.518; P value < 0.001].

Conclusion

We found that the use of ASI after PC diagnosis is associated with longer survival in PC patients. Additional well-designed randomized controlled studies are needed to confirm these findings in the future.

References

1. Rahib, L., B. D. Smith, R. Aizenberg, A. B. Rosenzweig, J. M. Fleshman and L. M. Matrisian (2014). "Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States" Cancer Res 74(11): 2913-2921.
2. Encarnación-Rosado, J. and A. C. Kimmelman (2021). "Harnessing metabolic dependencies in pancreatic cancers." Nature Reviews Gastroenterology & Hepatology 18(7): 482-492.
3. Thomas, D. and P. Radhakrishnan (2019). "Tumor-stromal crosstalk in pancreatic cancer and tissue fibrosis." Molecular cancer 18: 1-15.
4. Chauhan, V. P., J. D. Martin, H. Liu, D. A. Lacorre, S. R. Jain, S. V. Kozin, T. Stylianopoulos, A. S. Mousa, X. Han, P. Adstamongkonkul, Z. Popović, P. Huang, M. G. Bawendi, Y. Boucher and R. K. Jain (2013). "Angiotensin inhibition enhances drug delivery and potentiates chemotherapy by decompressing tumour blood vessels." Nat Commun 4: 2516.
5. Pinter, M. and R. K. Jain (2017). "Targeting the renin-angiotensin system to improve cancer treatment: Implications for immunotherapy." Sci Transl Med 9(410).

Introduction

Pancreatic ductal adenocarcinoma (PDAC) is a highly metastatic disease refractory to all targeted and immune therapies. However, our understanding of PDAC microenvironment especially the metastatic microenvironment is very limited partly due to the inaccessibility to metastatic tumor tissues. Here, we aim to carry out the first single-cell transcriptome analysis of PDAC metastatic microenvironment in matched primary tumor and liver metastasis tissues.

Aims & Methods

We collected synchronously resected PDAC primary tumors and matched liver metastases from four PDAC patients and performed single-cell RNA sequencing. We performed comparative analysis on both cellular composition and functional phenotyping between primary and metastatic tumors. We also performed trajectory analysis and cellular interactome analysis in the metastasis microenvironment.

Results

Epithelial cancer cells exhibited distinct transcriptomic profile in liver metastasis with clearly defined evolutionary routes from primary tumor. We identified specific subtypes of stromal and immune cells critical to the formation of the pro-tumor microenvironment in metastatic lesions, including RGS5⁺ cancer-associated fibroblasts, CCL18⁺ lipid-associated macrophages, S100A8⁺ neutrophils and FOXP3⁺ regulatory T cells. We also identified several new biomarkers associated with PDAC metastasis and poor prognosis, such as LITAF, SPRR1B, KLK7 and LGALS9. Cellular interactome analysis further revealed that the lack of tumor-immune cell interaction in metastatic tissues contributes to the formation of the immunosuppressive microenvironment.

Conclusion

Our study provides a comprehensive characterization of the transcriptional landscape of PDAC liver metastasis, which deepens our understanding of the mechanisms underlying the immunosuppressive microenvironment in metastatic PDAC and serves as a valuable resource for the design of novel targeted therapies.

Disclosure

No