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.

Clinical Case Summary

We describe a case of an 80-year-old woman with a history of bronchiectasis, nasal polyps, and chronic sinusitis who presented to the emergency department with diarrhea(>10 bowel movements/day),abdominal pain and estimated weight loss of 6 kg over one month. She was previously treated with antiparasitics without clinical improvement. Laboratory tests showed peripheral eosinophilia(10,400/mm3 eosinophils, 51.4% of total leukocytes). Viral serologies and autoimmune study were negative. Microbiological and parasitological analyses of stool samples were negative too. Immunoglobulin E levels were elevated. Abdominal computed tomography(CT) revealed thickening of the rectal ampulla and sigmoid colon. Upper gastrointestinal endoscopy did not show any abnormalities, but rectosigmoidoscopy revealed colorectal mucosa with millimetric whitish dots, some scattered erosions, and a 20 mm ulcer in the distal rectum that was biopsied. Histological evaluation showed inflammatory changes with predominance of eosinophilic polymorphonuclear cells(>50/field). Bone marrow study showed eosinophilic myeloid hyperplasia without blasts. No cytogenetic abnormalities were identified on chromosomal analysis. During hospitalization, she developed pruritic erythematous macules on the sacral region and inner thighs that gradually improved with topical steroids. Idiopathic hypereosinophilic syndrome with gastrointestinal involvement and possible cutaneous and pulmonar, was assumed. Prednisolone 40 mg/day was started with clinical and laboratory improvement, with complete resolution of peripheral eosinophilia. The diagnosis of idiopathic hypereosinophilic syndrome is a challenge because it is a diagnosis of exclusion and manifests in various ways depending on the affected system, with gastrointestinal involvement being possible, as in the case presented here. Recognition and early initiation of appropriate treatment can improve the survival and quality of life of these patients.

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

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.

Introduction

A previous study, which found that focal parenchymal atrophy of the pancreas is an indirect sign of small pancreatic cancer (PC), documented the changes in the pancreas until cancer onset.［1-3］ However, the pancreas atrophies and changes with age, so issues remain regarding the criteria for determining pancreatic atrophy as a sign of PC. The application of artificial intelligence (AI) technology to quantify changes in the pancreas over time and predict the onset of PC and high-risk groups for PC from objective indicators has the potential to facilitate early detection of PC.

Aims & Methods

Based on the rate of change in the pancreatic volume on computed tomography (CT) using AI technology, the present study predicted PC onset. Forty patients in whom PC was histopathologically diagnosed at Komagome Hospital between 2015 and 2023 and who had a history of three or more follow-up CT examinations over five years before PC onset (the PC group) were analyzed. Forty patients who underwent CT periodically for malignant skin disease but had no pancreatic disease were enrolled into a non-PC group. Patients with pancreatic carcinoma in situ (pancreatic intraepithelial neoplasm), an intraductal papillary mucinous neoplasm or chronic pancreatitis with multiple calcifications were excluded. Changes in the pancreatic volume in the groups over time were then compared using CT images taken one year or earlier before PC onset. The pancreatic volume was calculated using SYNAPSE VINCENT cloud (Fuji Film, Japan), an AI image application program. Age and pancreas volume were combined to create a scatter diagram, and the rate of pancreatic volume change (the temporal pancreatic volume change coefficient) was calculated from the regression line and compared.

Results

The lesion site in PC group included the head (n=17), body (n=7), and tail (n=16). The median maximum tumor diameter was 31 mm (interquartile range: 27-37). A comparison of the two groups found a cStage classification of IB, IIA, IIB, III, and IV in eight, ten, three, eight, and 11 patients, respectively. The median age was 72.5 and 72.5 years in the respective group (P=0.182). The male: female ratio was 23:17 and 24:16 (P=0.820), the median observation period was 83.5 and 107 months (P<0.05); the mean number of examinations was 10.7 and 18; the total number of CT examinations was 430 and 745; the mean total pancreatic volume was 74.4 and 78.15 ml (P<0.01 ); and the mean pancreatic volume change coefficient was -0.141 and -0.036 (P=0.01), respectively. The rate of decrease in the pancreatic volume was faster in the PC group with increasing age, the average being 8.46 ml over five years in the PC group compared to 2.16 ml in the non-PC group. The cutoff value for the coefficient of pancreatic volume change over time was set at -0.125. The sensitivity was 50%, the specificity was 90%, the positive predictive value was 83%, and the AUC value was 0.67.

Conclusion

In comparison with the age-related changes in the pancreas, the rate of decrease in the pancreatic volume was faster in the PC group, suggesting that PC onset may be predicted using images obtained one year or earlier before PC onset. These findings further suggested that identifying patients with a high risk of PC may be possible by creating a pancreatic volume histogram using AI technology based on age at the time of CT, intervals between past examinations, and the rate of decrease in the pancreatic volume.

References

［１］Nakahodo J, Kikuyama M, Nojiri S, et al. Pancreatology. 2020 Dec;20(8):1689-1697.
［２］Nakahodo J, Kikuyama M, Fukumura Y, et al. Pancreatology. 2022 Dec;22(8):1148-1158
［３］Kikuyama M, Nakahodo J, Honda G, et al. Pancreatology. 2023 Jun;23(4):420-428.