Clinical Case Summary

We report the case of 20 year old female patient with Crohn's disease who was shifted to Combo therapy (Infliximab + Azathioprine) for failing to reach mucosal healing on Conventional treatment. Quantiferon test, virology panel and a CT chest were negative prior to therapy. After one year of treatment she presented with high grade fever, weight loss, and abdominal pain. COVID-19 PCR and CT chest were negative. However, quantiferon test was positive. CTE abdomen showed marked thickening and stricture in the ileocecal area. Colonoscopy (Video available) was done to obtain biopsies; serpiginous ulcers with narrowing were noted. Histopathological assessment showed heavy Inflammatory cells with no more specification. A gene Xpert PCR on the tissue biopsy was positive for MTB. Given the septic state of the patient biological therapy was held for the duration of her treatment. She started Anti-TB and improved as the fever subsided and she gained weight. Colonoscopy was re-attempted after 4 months of treatment to confirm resolution (Video available). An impassable fibrotic stricture was noted the biopsy forceps could however be introduced and biopsies were obtained. Gene Xpert test was negative. The patient was started on Ustekinumab monotherapy with good response.
TB infection in patients on Anti-TNF therapy is a well-recognized potential side-effect of these drugs. To the best of our knowledge, this is the first reported case of Ileocecal TB on top of Crohn’s disease. A major challenge was weighing how much of the active inflammation shown in the endoscopy, biopsy and imaging was due to TB infection and how much was because of Crohn's disease activity. The time to re-initiate therapy was difficult given that the patient's bad general condition before starting antimicrobial treatment. While recommendations suggest starting immunosuppressives after 8 weeks of treatment in active tuberculosis, the evidence support this in pulmonary rather than extrapulmonary tuberculosis.

Introduction

Pancreatic neuroendocrine tumors (pNETs) are a heterogeneous group of tumors with different treatment options depending on pathological grading, clinical staging, and presence of symptoms related to hormonal secretion. Their classification is made on mitotic count and Ki-67 index.
The current standard for Grading assessment is analysing the material obtained from EUS-guided fine needle aspiration/biopsy (EUS-FNA/FNB). However this technique is not free from adverse events and could be challenging for NETs localization.
The evidence of high grade of fibrosis and microvascular density decrease (MVD) on tumor pathological specimens has led many authors to search for undirected malignant features of pNET extrapolated from non-invasive techniques. The introduction of ancillary techniques, such as second-generation contrast agents (CH-EUS), has improved study of pNET. Particularly, at CH-EUS examination contrast pattern well correlates with behaviour and grading of NETs. However, the use of contrast agents entails a prolongation of procedure time and additional costs. An innovative ultrasound Doppler technique, Detective Flow Imaging EUS (DFI-EUS), involves no additional time or cost as it doesn’t require the administration of contrast agent. There is still no standardisation of this technique and few studies have validated its use.

Aims & Methods

The aim of this study is to evaluate the DFI role in defining NET vascularization and its correlation with CH-EUS. The second aim of the study is to assess DFI role in predicting histological grading.
Single center retrospective analysis on consecutive patients with solid pancreatic lesions who underwent EUS at Therapeutic Digestive Endoscopy Unit of the Fondazione Policlinico Universitario Campus Bio-Medico in Rome.
After activation of DFI, each lesion was observed for at least 30 seconds. Lesions was classified into three grades, according to the degree of vascularisation at DFI: (grade 0 absence of microvascularization of the tumor; grade 1 minimal/isovascularization of the tumor; grade 2 markedly increased microvascularization).
All lesion with final hystological diagnosis of NET were enrolled.
Grading and Ki-67 index of tumors were reported.
Data about lesion’s features and procedure were collected.

Results

From April 2024 to February 2025, 17 patients were enrolled (58.8% male; mean age 57±12 years old). The majority of lesion (53%) were localized in the body of the pancreas and the mean lesion’ s size was 28±20 mm. The final histological diagnosis classified 50% lesions as G1, 38.8% G2 and 5.5% G3.
At the CEH-EUS the 70.6% of lesion showed hyper-enhancement. About the DFI evaluation the 17.6% of lesion was hypo-vascular, 17.6% Iso-vascular and 64.7% was hyper-vascular. There was excellent correlation between DFI characterization of the lesion and the CH-EUS (ICC 0.9)
Among the NET G1, 66.7% were Hypervascular at DFI and 33.3% Isovascular. Among the G2, 71.4% were Hypervascular at DFI and 28.6% Hypovascular. The only G3 lesion was Hypovascular.
There was inverse correlation between the NET grade and the DFI grade (Pearson coefficient -0.56; p 0.02).

Conclusion

DFI-EUS can provide a fast evaluation of the micro-vascularization of pNET with excellent correlation with CH-EUS. Hyper-vascular pattern at DFI correlates with low Ki-67 index.