Introduction

Pancreatic serous cystic neoplasms, benign lesions with distinct histologic appearance and very low malignant potential, represent 1-2% of pancreatic cysts.¹ Microcystic serous cystadenoma (SCA) is the most common subtype.² It may have a solid appearance on cross sectional imaging, which is only diagnostic in 50% of cases.³ In the absence of characteristic features on imaging, EUS-guided fine-needle aspiration (FNA) is the next diagnostic method of choice for large microcystic SCAs. However, cytology is often inconclusive and usually enough fluid is not attainable for chemistry analysis.⁴ Previous case series have shown that fine-needle biopsy (FNB) may be an effective method for diagnosing SCAs⁴; however, these studies were limited in patient number. We present a case series of 23 patients who underwent FNB for the diagnosis of suspected microcystic SCAs.

Aims & Methods

A single-center retrospective review of the electronic health record was performed on patients who underwent EUS to evaluate a solitary pancreatic lesion on cross sectional imaging. If EUS imaging was suggestive of a microcystic lesion and fluid aspiration was expected to be non-diagnostic or not feasible due to the small cystic components, the decision was made to pursue an FNB intraoperatively. FNB was performed on all patients using a 22-gauge fork tip biopsy needle, using either a transgastric or transduodenal approach. The acquired tissue was placed in formalin, underwent standard histologic handling, and was reviewed by an expert gastrointestinal pathologist. SCAs were diagnosed histologically by tight acinar tubules bordered by cuboidal cells with clear cytoplasms and round nuclei.

Results

A total of 23 patients were included (18 female). The mean age was 69.5 ± 12.2 years and the mean cyst size in its largest diameter was 33.3 ± 14 (range of 8-60mm). Seven of the lesions were in the tail, 8 in the body, and 8 in the head/genu. Histological diagnosis of SCA was established in 78% (18/23) of the lesions and no further surveillance or imaging was recommended for these patients. A mean number of 1.4 ± 0.63 (range of 1-3 passes) of passes were obtained. In one of the patients, only one pass was obtained due to intra-lesional bleeding after initial needle puncture. The patient did not require admission or any further intervention. There were no other adverse events noted, including bleeding and/or pancreatitis.

Conclusion

Our case series demonstrates that EUS-guided FNB is a safe and feasible method for diagnosing microcystic SCAs, despite previous literature suggesting high intraprocedural bleeding. This may be a cost-effective approach, since after the diagnosis is confirmed, follow-up imaging and surveillance is not needed. This may also prevent unnecessary surgical intervention in cases of larger lesions where EUS-guided FNA was non-diagnostic.

References

1. Kimura W, Moriya T, Hirai I, et al. Multicenter study of serous cystic neoplasm of the Japan pancreas society. Pancreas. 2012;41(3):380-387. doi:10.1097/MPA.0b013e31822a27db
2. Reid MD, Choi HJ, Memis B, et al. Serous Neoplasms of the Pancreas. American Journal of Surgical Pathology. 2015;39(12):1597-1610. doi:10.1097/PAS.0000000000000559
3. Tseng JF, Warshaw AL, Sahani D V, Lauwers GY, Rattner DW, Fernandez-del Castillo C. Serous cystadenoma of the pancreas: tumor growth rates and recommendations for treatment. Ann Surg. 2005;242(3):413-419; discussion 419-21. doi:10.1097/01.sla.0000179651.21193.2c
4. Manfrin E, Perini C, Di Stefano S, et al. Pseudo solid-appearing pancreatic serous microcystic adenomas: Histologic diagnosis with the EUS core biopsy fork-tip needle. Endosc Ultrasound. 2019;8(5):334-341. doi:10.4103/eus.eus_11_19

Disclosure

No conflict of interest to disclose.

Introduction

Janus kinase (JAK) inhibitors have emerged as an important therapeutic class for the management of several immune-mediated conditions, including inflammatory bowel disease (IBD), but they are associated with several side effects. A renewed attention to the safety profile of this drug class has been driven by increasing reports of JAK inhibitor-induced acneiform eruptions seen in clinical trials and real-life practice.

Aims & Methods

We aimed to investigate the epidemiology, clinical characteristics, and treatment outcomes of this condition in patients with IBD. This was an international, multicenter, retrospective cohort study that consecutively enrolled patients with IBD who were treated with JAK inhibitors and subsequently developed acne. The primary objective was to evaluate the clinical characteristics of acne presentation. Secondary objectives included determining acne prevalence, assessing its impact on quality of life, and evaluating the effectiveness of treatments.

Results

Of the 2,183 JAK inhibitor-treated patients with IBD screened, 272 developed acne and were included in the study. The crude prevalence rates of acne were 15.9% for upadacitinib, 4.3% for tofacitinib, and 1.9% for filgotinib, with dose-dependent relationships observed for upadacitinib and tofacitinib. Acne predominantly affected patients aged 30–50 years, with most cases being mild to moderate in severity. Acneiform eruptions most frequently involved the face (89%), followed by the back (33%) and chest (27%). Lesion characteristics were documented in 159 patients; papules (82%), pustules (52%), and comedones (42%) were the most frequently reported. In contrast, nodules (19%) and cysts (18%) – features associated with more severe disease – were less commonly observed. Among the 213 patients with available time-to-onset data, the median time to acne onset following JAK inhibitor initiation was 47 days (IQR: 28–98 days). Patients with a previous history of acne vulgaris were significantly more likely to develop severe drug-induced acne (p<0.0001). Although corticosteroids are known to contribute to acne, our data did not demonstrate an association between concomitant steroid use and increased acne severity. There was also no difference in time to onset or resolution of acne between the steroid-treated and non-steroid treated groups. A third of patients reported a negative impact on psychosocial well-being, and 40% required pharmacological intervention. Topical therapies were required for 106 patients (39%), with 52 (49%) showing acne improvement or resolution. Systemic oral agents were required for 38 patients (14%), including 25 patients who did not respond or had a partial response to topical therapies. Antibiotics were prescribed to 29 patients (most commonly from the tetracycline class), leading to acne improvement or resolution in 14 patients (48%). Oral isotretinoin was required for 8 patients (3%) and was effective in all but one patient. Eighteen percent of patients who developed acne (2.2% of total cohort) required a JAK inhibitor dose reduction or discontinuation, although most did not have severe disease.

Conclusion

This study is the first to characterise this adverse event in JAK inhibitor-treated patients with IBD and presents the largest cohort of JAK inhibitor-induced acne cases to date across all immune-mediated diseases. JAK inhibitor-induced acne is a common adverse effect resulting in significant psychological burden. Early identification, proactive counselling, and timely interventions, such as dose reduction or referral to dermatology, are crucial in managing this side effect.

Introduction

Eosinophilic esophagitis (EoE) is a chronic type 2 inflammatory disease with increasing incidence and prevalence. Patients with EoE usually present with symptoms of dysphagia that impact their quality of life. In the 3-part, Phase 3 LIBERTY EoE TREET study (NCT03633617), dupilumab improved histologic, symptomatic, and endoscopic aspects of EoE up to 52 weeks.

Aims & Methods

The aim of this analysis was to assess the effect of dupilumab on symptoms of dysphagia in the 28-week extended treatment period of LIBERTY EoE TREET in patients who switched from placebo to dupilumab at 24 weeks. In Parts A and B, patients received dupilumab 300 mg or placebo weekly (qw) for 24 weeks. Patients who completed Parts A and B entered Part C - a 28-week extended treatment period in which all patients received dupilumab 300 mg qw; patients entering Part C remained blinded to their treatment in Parts A and B. Dysphagia Symptom Questionnaire (DSQ) score and number of days with dysphagia (assessed using the DSQ) were calculated over a 14-day period. Percent change in DSQ score and in number of days with dysphagia from Week 24 through Week 52 vs the Week 24 baseline were assessed for patients who switched from placebo to dupilumab 300 mg qw at Week 24 and or continued on dupilumab 300 mg.

Results

Mean (SD) DSQ score after 24 weeks of placebo was 24.7 (19.6) and 21.5 (18.4) in Parts A (n=37) and B (n=37), respectively. Significant improvements in DSQ score were observed within 4 weeks of the switch to dupilumab 300 mg qw (mean percent reduction: 31.5% and 29.9%). After 28 weeks (at Week 52), mean percent reduction in DSQ score was 63.6% and 59.7%. After 24 weeks of placebo, mean (SD) days with dysphagia was 6.6 (4.7) and 6.0 (4.7) in Parts A and B, respectively. At Week 52, there was a 63.2% and 46.8% mean reduction in the number of days with dysphagia.

Conclusion

In patients who initially received 24 weeks of placebo, weekly treatment with dupilumab 300 mg resulted in rapid (within 4 weeks) and sustained (up to 28 weeks) improvement in symptoms of dysphagia as assessed by the DSQ score. The magnitude of the improvement in dysphagia observed after switching from placebo to dupilumab was similar to that seen at 4 weeks in patients who originally initiated dupilumab in Parts A and B of the study.

Disclosure

Dellon ES. Abbott, Abbvie, Adare/Ellodi, Aimmune, Akesobio, Alfasigma, ALK, Allakos, Amgen, Aqilion, Arena/Pfizer, Aslan, AstraZeneca, Avir, Biorasi, Calypso, Celgene/Receptos/BMS, Celldex, Dr. Falk Pharma, Eli Lilly, EsoCap, Eupraxia, Ferring, GSK, Gossamer Bio, Holoclara, Invea, Knightpoint, Landos, LucidDx, Morphic, Nexstone Immunology/Uniquity, Nutricia, Parexel/Calyx, Phathom, Regeneron, Revolo, Robarts/Alimentiv, Salix, Sanofi, Shire/Takeda, Target RWE, Upstream Bio – consultant. Adare/Ellodi, Allakos, Arena/Pfizer, AstraZeneca, Eupraxia, Ferring, GSK, Meritage, Miraca, Nutricia, Celgene/Receptos/BMS, Regeneron, Revolo, Shire/Takeda – research funding. Allakos, Aqilion, Holoclara, Invea – educational grants.
Chehade M. Adare Pharma Solutions/Ellodi, Allakos, AstraZeneca, BMS, Nexstone Immunology, Phathom, Recludix Pharma, Regeneron Pharmaceuticals Inc., Sanofi, and Shire/Takeda ‒ consultant. Adare Pharma Solutions/Ellodi, Allakos, AstraZeneca, Celgene/BMS, Danone, Regeneron Pharmaceuticals Inc., and Shire/Takeda ‒ research funding.
Bredenoord AJ. Alimentiv, Aqilion, AstraZeneca, Dr. Falk Pharma, Eupraxia, Laborie, Medtronic, Reckitt, Regeneron Pharmaceuticals Inc., and Sanofi ‒ consultant. Dr Falk Pharma, Norgine, Nutricia, Sanofi, SST, Regeneron Pharmaceuticals Inc., and Thelial ‒ research funding. Alimentiv, Aqilion, AstraZeneca, Dr Falk Pharma, Eupraxia, Laborie, Medtronic, Reckitt, Regeneron Pharmaceuticals Inc., and Sanofi ‒ speaker fees.
Spergel JM. Allakos, DBV Technologies, Novartis, Regeneron Pharmaceuticals Inc., and Shire/Takeda – consultant. DBV Technologies and Regeneron Pharmaceuticals Inc. ‒ research grant support.
Xia C, McCann E, Khodzhayev A, Radwan A. Regeneron Pharmaceuticals Inc. – employees and shareholders.
Tilton ST, Pela T, Jacob-Nara JA. Sanofi – employee, may hold stock and/or stock options in the company.

Introduction

Several changes in microbes of the gut and decreased diversity especially in inflammatory bowel disease (IBD) are well-known. The exact pathophysiological connection is lacking, but the systemic inflammation due to the microbial alterations are assumed.

Aims & Methods

This study aimed to perform analysis of faecal microbiota composition simultaneously with body composition and lipid characteristics in Crohn’s disease (CD) patients to find specific microbiota profiles connected to altered metabolism and obesity. In our prospective cohort study, CD patients were enrolled. At the inclusion, demographic and clinical data, blood, and faecal samples were obtained. Disease activity was assessed by CDAI, and SES-CD. Laboratory tests were made including C-reactive protein (CRP), albumin and lipids (triglyceride, cholesterol). Faecal bacterial composition was assessed using shotgun method. Each patient underwent a body composition analysis via bioelectrical impedance analysis. A nutritional questionnaire was filled by each subject.

Results

We analysed 27 CD patients in this study (median age was 35 IQR 13.5 years). A 44,4% and 27,3% of patients were obese based on BMI and VFA. Beta diversities were higher in non-obese patients (VTA, p<0,001), however relative abundances did not differ. Firmicutes has a lower, while C.innocuum has a higher abundance at high cholesterol level (p=0,001, p=0,0034). Adlercreutzia, B.longum and Blautia alterations were correlated with triglyceride level. Higher Clostridia (p=0,009) and B.schinkii (p=0,032) and lower Lactobacillus (p=0,035) were connected to high VFA. B.bifidum had richness amongst low-weight patients (p=0,01). Beside Clostridia, Eubacteriales and R.hominis also correlated with waist-hip ratio (p=0,04, p=0,04 and p=0.048). Higher body fat mass was paired with increased B.schinkii (p=0,021) and decreased L.paragasseri (p=0,015) and R.intestinalis (p=0,035). Disease activity was coupled with dysbiotic elements. Microbiota alterations were found during different treatments.

Table 1. Baseline demographic and clinical characteristics of the study population [n = 27]

Conclusion

Changes in Blautia, Lactobacillus, Clostridia and Bifidobacterium abundances in obesity highlight the importance of gut microbiota in diseases with similar inflammatory background. It suggests to treat obesity to achive better disease contol in IBD and it helps to develop new therapeutic approaches, such as pre- or probiotics or personalized faecal microbiota transplantation.

Clinical Case Summary

A 77-year-old man underwent liver transplantation in 2008 due to alcoholic cirrhosis associated with hemochromatosis, and was taking tacrolimus and mycophenolate mofetil since that.
He was admitted in the Emergency Department in February 2023 with right upper quadrant abdominal pain and diarrhea for one week. Abdominal computed tomography(CT) showed ileal thickening. Laboratory tests revealed leukocytosis(19,000 leukocytes/mm3) and elevated C-reactive protein(16 mg/dL). Acute gastroenteritis was assumed and he was discharged on metronidazole with clinical improvement. One month later, he returned to the Emergency Department with abdominal pain for two days. CT revealed concentric wall thickening of the last ileal loop and a probable enteromesenteric fistula. He was admitted for further evaluation. Colonoscopy revealed deep mucosal ulceration of the terminal ileum. After colonoscopy, his abdominal pain worsened, so he repeated the abdominal CT, which showed a new organized collection in the right flank measuring 63 mm and small gas bubbles of pneumoperitoneum in the right upper quadrant. He underwent ileocecal resection with terminal ileostomy, and the histopathological evaluation revealed a neoplasm composed of atypical lymphoid proliferation, with positive immunohistochemistry for CD45, CD20, CD79a, BCL2, and BCL6, compatible with diffuse large B-cell lymphoma. After staging and exclusion of distant disease, the patient was proposed for chemotherapy following reduction of immunosuppression.
The clinical presentation of Inflammatory Bowel Disease can be quite heterogeneous and several pathologies can mimic its clinical, endoscopic, and/or histological findings. This case illustrates the importance of considering the diagnosis of small bowel lymphoma as a differential diagnosis of Crohn's disease, especially in elderly patients with risk factors, such as chronic immunosuppression.