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.

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

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.

Introduction

Fatigue is commonly reported by Crohn's Disease patients even in the absence of disease activity.
Other possible causative factors need to be determined in order to successfully address this problem, which significantly affects patients' lives even when treatment targets have been achieved.
Sarcopenia and Depression are also common in Crohn's Disease and possibly related to fatigue.

Aims & Methods

Consecutive patients with Crohn's Disease who came to the infusion center to receive maintenance intravenous infliximab treatment were included. All participants had to be in full clinical (HBI <5), biological (C-RP < 0.5 mg/dL and/or fecal calprotectin <100 μg/mg) , endoscopic (SES-CD 0-2), or enterographic remission in the past 6 months. Anthropometric measurements (Weight, Height, Body Mass Index, Circumcenter waist, hips, gastrocnemius, Waist to Hip Ratio), Body Composition Measurements (Body Fat, Total Body Water, Body Fat Mass Index, Lean Body Mass), Physical Activity Tests (Handgrip Strength test, 6-meter Walk Test, One Leg Standing test, 30-second Chair Stand test) and Questionnaires related to Sarcopenia ( Lawton Instrumental Activities of Daily Living Scale-LIADLS, Activities Daily Living Scale-ADLS, Dixon's Diet Score-DASH, Mini Nutritional Assessment-MNA, Mediterranean Diet Serving Score MDSS, the Mind Diet Score-MDS) were conducted. We used the Functional Assessment of Chronic Illness Therapy-Fatigue scale (FACIT-F) to measure fatigue. We used the Hamilton Depression Rating Scale (HAM-D) to assess for depression. Linear regression analysis was used to assess the impact of sarcopenia and depression on fatigue.

Results

A total of 39 patients were included: mean age 38.6 years, mean body weight 80 Kg, median disease duration 9 years, female 22 (56,%), male 17 (44%).
We included patients with ileal disease (48%), perianal disease (28%), stomas (8%), extraintestinal manifestations (12%), on second or third biologic therapy (56%), smokers (10%).
Median C-RP was 0.13 mg/dL and median albumin was 4.5 g/dL.
Sarcopenia was almost non existent by all measures: Indicatively, Median Max Hand Grip was 25.7 (range 10.8-57.4).
Median FACIT-F was 45 (range 7-52).
Median HAM-D was 4 (range 0-25).
There was no correlation between FACIT-F and Sarcopenia (Max Hand Grip): p=0,280, β coefficient = 0,159.
There was a correlation between FACIT-F and HAM-D: p<0,001, β coefficient = -1,576.
Interestingly there was also a correlation between HAM-D and max Hand Grip: p=0,029, β coefficient = -0,804.

Conclusion

We found expectantly low (though not in all patients) estimates of sarcopenia, fatigue and depression in this selected group of Crohn's Disease patients in complete remission receiving intravenous infliximab.
Fatigue could not be attributed to sarcopenia. On the contrary depression seemed to be one of the main determinants of fatigue.
Multidisciplinary care of fatigue should include psychological evaluation and possible intervention.
Further research in the field of fatigue related to Inflammatory Bowel Disease is needed.

Clinical Case Summary

Pancreatic cystic lymphangioma is extremely rare, accounting for less than 5% of pancreatic cystic neoplasms and less than 1% of all lymphangiomas.¹
A 51-year-old female presented with complaints of recurrent abdominal pain for 4 weeks. She was previously misdiagnosed as acute pancreatitis complicated with pancreatic pseudocyst. There was no history of trauma. Dynamic MRI on the abdomen revealed a large, encysted collection at the pancreatic body suggesting a query pancreatic pseudocyst. EUS examination revealed a large cystic lesion at the body of the pancreas. The cyst was multilocular with characteristic multiple thin septa within the lesion (Figure 1). EUS-FNA with 22-G needle was done with aspiration of about 20 ml of cyst fluid, divided into two bottles, one for cytology examination and mucin stain while the second bottle for Amylase, CEA and TG levels. Aspiration fluid was serous yellowish in colour, with negative string sign. Also, a large focal lesion within the spleen was also seen.The biochemical evaluation of the aspirated cystic fluid revealed low amylase and CEA, and high TG levels. Cytopathological examination showed fairly cellular material featuring numerous predominantly small lymphocytes. There were no epithelial, atypical, or malignant cells. IHC staining was positive for CD-31 and CD2-40. Alcian blue mucin stain was negative. The diagnosis of pancreatic cystic lymphangioma was made based on EUS, cytological and biochemical examination with IHC features. Since, lymphangiomas are benign tumors without malignant potential, treatment depends on the symptoms. Lymphangioma can encroach on adjacent organs and need surgical resection. To relieve symptoms of abdominal, distal pancreatectomy and splenectomy was discussed, but patient refuse surgery. Multidisciplinary team decided a conservative management with a follow-up by dynamic MRI and EUS within 6 months.

References

1. Chen D, Feng X, Lv Z, Xu X, Ding C, Wu J. Cystic lymphangioma of pancreas: A rare case report and review of the literature. Medicine (Baltimore). 2018 Jul;97(28): e11238. doi: 10.1097/MD.0000000000011238.