Introduction

IPMNs are mucin-producing subtypes of pancreatic cysts considered a potential precursors of pancreatic cancer accounting for 8% of all pancreatic malignancies. The molecular mechanisms and biological factors involved in the progression of IPMN are still unknown. In previous studies, modifiable risk factors (e.g., smoking) and protective factors (e.g., ACE inhibitors) have been investigated to slow down or prevent the IPMN progression. The aim of this study is to investigate the association between modifiable lifestyle factors (smoking and alcohol consumption) and the use of commonly prescribed medications (aspirin, ACE -inhibitors, angiotensin- II -receptor antagonists, and statins) and the progression of IPMN.

Aims & Methods

This was a monocentric retrospective cohort study. The study included patients who underwent radiological and clinical examinations at time 0 and at the 3-year follow-up visits. Demographic data (sex, age, weight, and height), IPMN characteristics (type of IPMN and radiological characteristics at baseline), lifestyle factors (smoking and alcohol consumption), and medication use (aspirin, ACE -I, ARBs, and statins) were recorded. Clinical and radiological characteristics were recorded at the 3-year follow-up to detect progression of IPMN (defined as the presence of high-risk stigmata and/or features of concern). Statistical analysis was performed using SPSS 20. Descriptive data are presented as mean±standard deviation and median with range or percentage. Categorical data were compared using the χ₂ test. Multivariate logistic regression analysis was performed to adjust for confounding factors (age, sex, and IPMN subtype). A p value < 0.05 was considered statistically significant.

Results

126 patients were included in the study. Patient characteristics are summarized in Table 1. Smoking (p 0.036; OR 5.7, IC95% 1.11-29.04), heavy alcohol use (p 0.027; OR 4.8, IC95% 1.10-9.50), and use of ARB (p 0.048; OR 3.52, IC95% 1.85-14.50) were associated with progression of IPMN. Statin use was associated with a lower risk of IPMN progression (p 0.043; OR 0.154, IC95% 0.021-0.978). Body weight, aspirin, ACEi, and low alcohol intake were not statistically associated with IPMN natural history.

Table 1. Patients’ characteristics.
Demographics: No. of patients, n Age (years), mean ± SD Sex (men), n (%)	126 65 ± 11 46 (36,5%)
Type of IPMN: Main duct-IPMN, n (%) Side Branches-IPMN, n (%) Mixed type-IPMN, n (%)	106 (84%) 7 (5.5%) 13 (10,5%)
BMI: 18-25 25-30 30-35 35-40 >40 Alcohol intake: Low-dose (<2 units/day) High-dose (>2 units/day) Smoking habit:	65 (56%) 40 (34,5%) 7 (6%) 4 (3,5%) 0 88 (69,8%) 17 (13,5%) 24 (19%)
Drugs intake: ACE-I Aspirin Sartans ARB	21 (16,5%) 26 (20,5%) 34 (26,9%) 34 (26,9%)

Conclusion

With the limitations resulting from the small sample size and retrospective design of the study, smoking, heavy alcohol consumption, and ARBi use appear to be risk factors for progression of IPMN. In contrast, statin use was found to be a protective factor for IPMN progression. Prospective studies are needed to confirm these preliminary data.

Clinical Case Summary

We present the case of a 68-year-old man who presents with abdominal pain and constitutional syndrome after two months. Faecal occult blood test is positive, so a gastrointestinal endoscopic study is proposed. Complete colonoscopy is normal. In the upper endoscopy, dilated lymphatics with irregular appearance are observed in the second duodenal portion, so biopsies are taken. Histological study of duodenal biopsies shows infiltration by metastatic adenocarcinoma of the lung (positive cytokeratin 7 and TTF1). The study is completed with computed tomography (CT), which objectifies thoracic adenopathies and a mass in the right lower lobe compatible with lung neoplasia.
Metastatic spread of lung cancer may involve any organ, but metastases to the gastrointestinal tract, particularly the duodenum, are considered unusual.¹ Small bowel metastases usually originate from melanoma or carcinoma of the cervix, uteri, ovary, or breast.¹ However, intestinal metastases have been described in 11% of autopsy lung cancer studies, suggesting that this situation is not as rare as it is thought to be.¹ This could be explained because intestinal metastases are often asymptomatic.¹ Less than 0.5% of the metastatic cases are symptomatic.²
When metastasis to the gastrointestinal tract occurs, the findings are nonspecific. The most common symptoms are abdominal pain, cramping, nausea, vomiting, weight loss, and constipation.³ Possible complications of these metastases include perforation, obstruction, and hemorrhage.^1,3 Abdominal imaging studies, as the CT, have a low sensitivity for detecting gastrointestinal metastases, visualized as a wall thickening or masses.³ However, previous cases of gastrointestinal metastases of lung cancer with the appearance of duodenal lymphatic ectasia have not been found in the literature. So, this case should be taken into account to remember that intestinal lymphangiectasia, albeit infrequently, could be the first sign of malignancy.

References

1. Lin HC, Yu CP, Lin HA, Lee HS. A case of lung cancer metastasized to the gastrointestinal anastomosis site where the primary gastric cancer was resected 17 years ago. Lung Cancer 2011;72(2):255-7. doi: 10.1016/j.lungcan.2011.02.005.
2. Tanriverdi O, Alkan A, Ozseker B, Solak-Ozseker H, Kilinc RM. Synchronous duodenum and descending colon metastasis from primary lung neuroendocrine small-cell carcinoma: A case report and review of the literature. J Oncol Pharm Pract 2020;26(6):1524-9. doi: 10.1177/1078155220904133.
3. Ahmed A, Nasir UM, Donna PD, Swantic V, Ahmed S, Lenza C. A rare presentation of poorly differentiated lung carcinoma with duodenal metastasis and literature review. Case Rep Gastroenterol 2020;14(1):186-96. doi: 10.1159/000506927.

Introduction

Eosinophilic esophagitis (EoE) is a chronic, allergic inflammatory disease of the esophagus. Major adverse cardiovascular events (MACE) have been associated with diseases of chronic inflammation. Data on MACE from large population-based cohorts of biopsy-proven EoE are lacking.

Aims & Methods

The aim of this study was to investigate the association between EoE and MACE. It included all Swedish adults with EoE (1990-2017) without a record of previous cardiovascular disease (CVD) (n=1,546, with follow-up until 2019). EoE was defined from prospectively recorded esophageal histopathology reports from all Swedish pathology departments (n=28) in the Epidemiology Strengthened by Histopathology Reports in Sweden (ESPRESSO) cohort. Individuals with EoE were matched with up to five general population reference individuals (n=7,281) for age, sex, calendar year and county without EoE or CVD. Multivariable-adjusted hazard ratios (aHRs) for MACEs (any of ischemic heart disease, congestive heart failure, stroke and cardiovascular mortality) were calculated using Cox proportional hazards models. In secondary analyses, individuals with EoE were compared to their siblings to account for residual confounding.

Results

The majority of individuals with EoE were male (75%), and the median age at EoE diagnosis was 37 years (IQR 19-51). Over a median of 6.0 (IQR 4.6-8.0) years of follow-up, 65 (4.2%) MACE events were observed in patients with EoE and 225 (3.1%) in reference individuals, corresponding to 6.4 vs. 4.7 events per 1,000 person-years (incidence rate difference: 1.7, 95%CI=0.0-3.4), respectively. No significantly higher overall risk (aHR=1.14, 95%CI=0.86-1.51) of MACE outcomes. No significant differences between age, sex and follow-up time were observed. When adjusting for relevant CVD medication and sibling comparison, results were similar.

Table 1 Incidence Rates, Absolute Rate Differences and Hazard Ratios for incident Major Adverse Cardiovascular Events in patients with Eosinophilic Esophagitis compared to general population reference individuals 1990-2019
		Reference individuals	EoE
		N=7 281	N=1 546
	MACE outcomes*
	Incident events (%)	226	65
	Incidence rate per 1000 py (95%CI)	4.7 (4.1-5.4)	6.4 (4.9-8.1)
	Absolute rate difference per 1000 py (95%CI)	0 (ref.)	1.7 (0-3.4)
	Unadjusted HR# (95%CI)	1 (ref.)	1.37 (1.04-1.80)
	Adjusted HR (95%CI)	1 (ref.)	1.14 (0.86-1.51)

CI, confidence interval; EoE, eosinophilic esophagitis; HR, hazard ratio; MACE, major adverse cardiovascular events; py, person-years

^*Includes ischemic heart disease, congestive heart failure, stroke and cardiovascular mortality.
^#Adjusted for age, sex, calendar year, county of residence at index date, country of birth (Nordic country or other), educational level (compulsory school, upper secondary school or college/university), ≥1 metabolic disease (diabetes, obesity, hypertension or dyslipidemia), chronic kidney disease, atopic dermatitis, celiac disease and chronic respiratory disease (chronic obstructive pulmonary disease or asthma) diagnosis.

Conclusion

Individuals with biopsy-proven EoE had no increased risk of MACE outcomes compared to general population or sibling comparators. The absence of any association with MACEs in our study may be reassuring for patients with EoE.

Disclosure

Dr. Forss has served as a speaker and advisory board member for Janssen corporation. Dr. Uchida is a medical advisor for Sanofi-Regeneron and AstraZeneca. Dr. Roelstraete has no conflicts of interest. Dr. Ebrahimi has served as advisory board member for Boehringer Ingelheim. Dr. Garber do not have any conflicts of interest to declare related to this study. Dr. Sundström reports stock ownership in Anagram kommunikation AB and Symptoms Europe AB outside the submitted work. JFL has coordinated an unrelated study on behalf of the Swedish IBD quality register (SWIBREG). This study received funding from Janssen corporation. JFL has also received financial support from MSD to develop a paper reviewing national healthcare registers in China, and has ongoing discussions with Takeda about a celiac disease project.

Introduction

Despite EUS-guided drainage (EUS-FCD) is the preferred modality for management of peripancreatic fluid collections (PFCs), factors predicting the need for step-up to additional procedures (including radiology, surgery or additional endoscopies) are retrospectively explored in studies restricted to Lumen Apposing Metal Stents (LAMS) or excluding pseudocysts and post-surgical collections, which might require a step-up as well.

Aims & Methods

All consecutive candidates to EUS-FCD with either LAMS or Double-pigtail Plastic Stents (DPPS) between 2020-2023 were included in a Prospective Registry of Therapeutic EUS (PROTECT). The role of baseline clinical and morphological factors, including the Quadrant / Necrosis / Infection (QNI) score, in predicting the need for any step-up to additional procedures was evaluated by stepwise logistic regression.

Results

Twenty-three post-surgical PFCs, 19 pseudocysts and 18 walled-off necrosis [WOPN]) were included, 42% treated with LAMS and 58% with DPPS based on morphology. Clinical success was 92.9%, but 38% of patients required a step-up to necrosectomy (26.7%) or additional procedures. Patients requiring step-up versus those sufficing drainage had a higher number of quadrants involved (OR=3.6 [1.5-8.4]), a more frequent paracolic extension (OR=6 [1.4-26]), a higher necrosis content (>30%, OR=7.2 [1.8-28.4] ; >60% OR=25.2 [4.2-153]) and were in the high-risk group according to the QNI score, with no difference in the diameter and rate of superinfection. At multivariate analysis, being in the high-risk QNI group was the only independent predictor of step-up (OR=9.8 [2.9-32.9]). The score however was not able to stratify in analyses restricted to WOPN only or LAMS only. High-risk QNI patients presented also a longer hospital stay (17.5 [8-45] vs 4 [2-6.5], p=0,001), without any difference in ICU stay and nutritional support.

Conclusion

In this prospective series of consecutive non-selective PFCs undergoing EUS-FCD, QNI score was the only independent predictor of any need for step-up to additional procedures, and strongly correlated to the EUS-FCD allocation to LAMS versus DPPS, unravelling a potential additional utility.

Disclosure

GV reports travel grants from Pentax Medical, Boston Scientific and Euromedical, and lecture fees by Boston Scientific.
All the other authors ​declare no conflict of interest.

Introduction

Increased lipase level is a serological hallmark of the diagnosis of acute pancreatitis (AP) but can be detected in various other diseases associated with lipase leakage due to inflammation of organs surrounding the pancreas or reduced renal clearance and/or hepatic metabolism. This non-pancreatic hyperlipasemia (NPHL) is puzzling for attending physicians during the diagnostic procedure for AP. It would be clinically beneficial to identify the clinical and laboratory variables that hinder the accuracy of lipase diagnosis with the aim of improve it. A more precise description of the NPHL condition could potentially provide prognostic factors for adverse outcomes which is currently lacking.

Aims & Methods

We aimed to provide a detailed clinical and laboratory characterization of a large prospective NPHL patient cohort and assess parameters determining disease outcomes.
A Hungarian patient cohort with serum lipase levels at least three times higher than the upper limit of normal (ULN) was prospectively evaluated over 31 months. Patients were identified using daily electronic laboratory reports developed to support an ongoing observational, multicenter, prospective cohort study called the EASY trial (ISRCTN10525246) to establish a simple, easy, and accurate clinical scoring system for early prognostication of AP. Diagnosis of NPHL was established based on ≥ 3 × ULN serum lipase level in the absence of abdominal pain or abdominal imaging results characteristic of pancreatitis.

Results

A total of 808 patients [male, n = 420 (52%); median age (IQR): 65 (51-75) years] were diagnosed with ≥ 3 × ULN serum lipase levels. A total of 392 patients had AP, whereas 401 had NPHL with more than 20 different etiologies. Sepsis and acute kidney injury (AKI) were the most prevalent etiologies of NPHL (27.7% and 33.2%, respectively). The best discriminative cut-off value for lipase was ≥ 666 U/L (sensitivity, 71.4%; specificity, 88.8%). The presence of AKI or sepsis negatively affected the diagnostic performance of lipase. NPHL was associated with a higher in-hospital mortality than AP (22.4% vs 5.1%, P < 0.001). In multivariate binary logistic regression, not lipase but increased amylase level (> 244 U/L) and neutrophil-to-lymphocyte ratio (NLR) (> 10.37, OR: 3.71, 95%CI: 2.006-6.863, P < 0.001), decreased albumin level, age, and presence of sepsis were independent risk factors for in-hospital mortality in NPHL.

Conclusion

NPHL is a common cause of lipase elevation and is associated with high mortality rates. Increased NLR value was associated with the highest mortality risk. The presence of sepsis/AKI significantly deteriorates the serological differentiation of AP from NPHL.

Introduction

Surveillance colonoscopy in patients with Inflammatory Bowel Disease (IBD) poses a unique challenge due to the subtle nature of flat dysplasia. But this challenge is further compounded by the number of additional lesions seen as a result of inflammation, such as pseudo-polyps and inflammatory polyps which can result in additional biopsies or unnecessary resection. Computer aided diagnosis (CADx) could improve lesion characterisation in this cohort of patients but a dedicated CADx algorithm has yet to be developed. Here we compare the performance of endoscopists and an existing generic colon CADx algorithm on lesion characterisation in IBD patients.

Aims & Methods

In phase 1, endoscopist performance on image based characterisation was assessed using still images of lesions in patients with IBD. Frames were taken in both white light imaging (WLI) and Image Enhancement (IE). Images were checked by an independent reviewer for the quality of images. Characterisation was then performed by 12 endoscopists (6 experts who regularly perform IBD surveillance and 6 non-expert) who categorised them as neoplastic (adenoma with low or high grade dysplasia) or non-neoplastic (hyperplastic, regenerative, inflammatory or pseudo-polyps).

In phase 2, an existing generic colon CADx algorithm was used in video based analysis of prospectively collected IBD colonoscopy videos. Lesions were characterised as neoplastic or non-neoplastic. Ground truth in both phases was histology.

Results

In phase 1, 57 lesions (34 neoplastic, 23 non-neoplastic) were characterised by endoscopists. For non-experts, sensitivity, specificity and accuracy were 73.0%, 55.3% and 65.9% respectively on white light and 73.9%, 49.1% and 64.7% on IE. For expert endoscopists, sensitivity, specificity and accuracy were 70.1%, 66.7% and 68.7% respectively on WLI and 78.3%, 60.8% and 72.0% on IE.

In phase 2, full withdrawal videos in 20 patients undergoing surveillance colonoscopy were collected. 17 patients had Ulcerative Colitis, 3 patients had Crohn’s disease. 86 lesions were identified (21 neoplastic, 65 non-neoplastic). Video based CADx performance for sensitivity, specificity and accuracy was 88.89%, 80.64% and 74.44% respectively.

	Non-expert		Expert		CADx
	WLI	IE	WLI	IE
Sensitivity (%)	73.0	73.9	70.1	78.3	88.9%
Specificity (%)	55.3	49.1	66.7	60.8	80.6%
Accuracy (%)	65.9	64.7	68.7	72.0	74.4%
Table 1. Performance of endoscopists vs CADx

Conclusion

Our data highlights the challenges of lesion characterisation IBD patients, with a low sensitivity and specificity in both experts and non-experts. In particular, non-experts have a very low specificity meaning there may be a high number of unnecessary resections/biopsies performed. A generic CADx algorithm performed better than endoscopists and with dedicated training of this algorithm with IBD lesions could further improve characterisation and reduce the number of non-neoplastic lesions which are removed.

Disclosure

Professor Bhandari has received research grants or is the advisory board for Fujifilm, Boston, Olympus, Pentax, 3-D matrix, NEC (Japan), Medtronic

Introduction

Pancreatic cancer is a highly fatal disease with a 5-year survival rate of approximately 10%. Pancreatic ductal adenocarcinoma (PDAC) is characterized by abundant collagen deposition in the tumor stroma. However, the precise impact of this phenomenon on PDAC remains unclear.

Aims & Methods

This study aimed to clarify the interactive relationship between tumor stromal collagen and its molecular characteristics, immune characteristics, and tumor progression in human PDAC. The goal is to elucidate the mechanism of fibrosis in PDAC. A comprehensive examination was performed using a molecular pathological epidemiology database on 169 cases with resected PDAC.
Among 234 patients who underwent pancreatectomy surgery between April 2008 and March 2017 at Kobe University, 169 conventional PDAC patients were analyzed. Patients with special type pancreatic cancers, with stageⅣ PDAC, who underwent preoperative radiation, and without available FFPE samples were excluded. The following information was collected retrospectively about these patients: age, gender, body mass index, family history, blood test results, surgical pathology specimen, and treatment course.
We quantified the amount of tumor stromal collagen by digitally processing EVG-stained whole-section slides. Gene alterations (KRAS, TP53, CKDN2A/p16, and SMAD4), immune parameters (CD4+ tumor-infiltrating lymphocytes [TILs], CD8+ TILs, FOXP3+ TILs, and tertiary lymphoid structures), and marker of cancer-associated fibroblasts such as αSMA were evaluated by immunohistochemistry, next-generation sequencing, and droplet digital PCR.

Results

Multivariate logistic regression analysis revealed that low stromal collagen levels were linked to poor differentiation (P=0.008) and CDKN2A/p16 alteration (P=0.03) of PDAC. Additionally, low stromal collagen levels were found to be an independent poor prognostic factor. The overall survival of such patients was significantly shorter (22.1 months vs. 38.0 months, P=0.001).
Regarding those who underwent chemotherapy, low amounts of stromal collagen were linked to poor prognosis in the S-1 (P= 0.005) and gemcitabine (P= 0.007) treatment groups. Furthermore, they were linked to low levels of CD4+ tumor-infiltrating lymphocytes (TILs) (P=0.046), CD8+ TILs (P=0.09), and tertiary lymphoid structures (P=0.001).
The mechanism by which fibrosis is associated with prognosis is not well-defined. The components of tumor microenvironment are diverse, including cancer cells, fibroblasts, immunocompetent cells, and extracellular matrix. Thus, we explored comprehensively the factors and mechanisms that define fibrosis with Spatial Transcriptome. Gene expression analysis was performed using two sets of four cases with different amounts of stromal collagen. The gene expression could be classified into 7 clusters. The cancer cells in the low amounts group consisted of one cluster and those in the high amounts group consisted of two clusters on the hand. Enrichment analysis on the distinctive cluster in the high amounts group revealed that it was genes that activated the TGFβ pathway.

Conclusion

The amount of tumor stromal collagen varies in tumor characteristics, prognosis, and response to postoperative chemotherapy in PDAC, and may affect the modulation of the tumor immune microenvironment. We found that there is a group of genes that are characteristically expressed in PDAC with high amounts of stromal collagen and a good prognosis. Further studies will be conducted to elucidate the mechanisms that regulate fibrosis.