Clinical Case Summary

A 62-year-old Italian woman with suspected Crohn’s disease (CD) was referred to our inflammatory bowel disease outpatient clinic in August 2022. She presented with abdominal pain, weight loss and vomiting. Initial laboratory evaluation revealed an elevated white blood cell count (12× 10^9/L), anemia with hemoglobin of 10 g/dL, a normal creatinine and liver function, a high C-reactive protein of 10 mg/L (reference range <7.4 mg/L) and a faecal calprotectin of 139 µg/g. Moreover, a QuantiFERON-TB Gold+ test was performed to exclude intestinal tuberculosis and resulted negative. Imaging studies (computed tomography, intestinal ultrasound and magnetic resonance enterography) revealed focal thickening and strictures in the terminal ileum and colon (A, B, C, D). Colonoscopy, performed with a gastroscope of 9.2 mm of diameter, confirmed the presence of a passable stenosis in the rectum (E) and a non-passable stenosis of the sigmoid colon (F). Despite inconclusive histological findings, a multidisciplinary team recommended surgery due to worsening symptoms. Unexpectedly, histological analysis of surgical specimens revealed metastases from breast lobular adenocarcinoma (BLAC). After surgery the patient was treated with systemic therapy (ribociclib and letrozole), with stable disease at 1-year follow-up.
Metastasising of breast cancer to the gastrointestinal tract, especially BLAC, is possibile even if is rare. It could be the first manifestation of the tumor and may mimic symptoms and imaging appearance of CD, resulting in challenging diagnosis. False-negative histology at endoscopic specimens warrants consideration of alternative diagnoses, and histological diagnosis sometimes is only possible with surgery.

References

A. Computed tomography scan, in coronal (left) and transversal (right) sections, show both a thickening of the last ileal loop for 5 cm in lenght with enhancement in the arterial phase (red arrows) and a concentric parietal thickening of the sigmoid colon (yellow arrows).
B. Intestinal ultrasound show thickening of the terminal ileum (red dotted line) with increased vascularization and upstream dilation (green dotted line) (left) and parietal thickening of the sigmoid colon up to 7.9 mm (yellow dotted line) with increased vascularization in the submucosa and narrowing of the lumen (right).
C. Magnetic resonance enterography, in coronal (left) and transversal (right) sections, show concentric stricture with enhancement of the ileo-cecal valve and terminal ileum (red arrows) and stricture of the sigmoid colon extending over a length of 7 cm (yellow arrows).
D. Intestinal ultrasound (left) and magnetic resonance enterography (right) shows a wall thickening of the rectum up to 7.3 mm (red dotted lines).
E. Endoscopic view of a passable stenosis of the rectum extending from 12 to 10 cm from the anal verge.
F. Endoscopic view of a non-passable stenosis of the sigmoid colon at 30 cm from the anal verge.

Disclosure

S. Bencardino and A. Zilli declares no conflict of interest. M. Allocca received consulting fees from Nikkiso Europe, Mundipharma, Janssen, Abbvie, and Pfizer. F. Furfaro received consulting fees from Amgen, Abbvie, Janssen and Pfizer. F. D’Amico has served as a speaker for Sandoz, Janssen, Galapagos, and Omega Pharma; he also served as advisory board member for Ferring, Galapagos, Abbvie, Janssen and Nestlè.

Clinical Case Summary

K.D.B.B., a 32-years old woman diagnosed with Crohn’s disease (CD) for 4 years. The patient has been receiving Ustekinumab every 2 months due to recurrent anorectal fistula. In 2022, she underwent a seton placement. Since perianal inflammatory signs persisted, the dose was optimized to a monthly administration. After 5 months, fistula had healed and the seton was removed. At the beginning of 2024, patient presented cramps, abdominal distension, nausea, diarrhea, and elevated inflammatory markers. Consequently, therapy was switched to Adalimumab, which demonstrated a good response: CD remission, 8 kg weight gain over 10 months, disappearance of abdominal symptoms, and regular bowel habits (Bristol Stool Type 4). At the end of 2024, she returned with abdominal pain and discharge from the fistula. An enterotomography and ileocolonoscopy were performed revealing ileal stenosis. Then, a right laparoscopic ileocolectomy was indicated. Immunohistochemical analysis of the surgical specimen showed positivity for CD-56 and chromogranin, as well as a cell proliferation index (Ki-67) of 1%, which is compatible with a well-differentiated grade 1 neuroendocrine tumor (NET) at the apex of the cecal appendix. The patient was referred to an oncologist and is being followed up, taking Adalimumab 40 mg every 14 days, with no abdominal complaints and improvement in perianal discharge. The aim of this report is to describe the findings of NET in a CD patient. The cecal appendix is the second most frequent site of NETs in the entire digestive tract (25-30%) and they are usually diagnosed incidentally during appendectomies or other abdominal surgeries as reported in this clinical case [1]. The chronic inflammation of CD can favor tumor development [2]. However, the association between NET and CD is not yet well established [3], highlighting the need for more studies and reports in order to clarify and understand the pathophysiology of CD and define effective therapeutic approaches.

References

[1] Silva, R. L. da, Linhares, E., Gonçalves, R., & Ramos, C. (2010). TUMORES NEUROENDÓCRINOS DO APÊNDICE CECAL: EXPERIÊNCIA DO INSTITUTO NACIONAL DE CÂNCER. Revista Brasileira de Cancerologia, 56(4), 463–470. https://doi.org/10.32635/2176-9745.rbc.2010v56n4.696
‌[2] G. Åkerström, & Hellman, P. (2024). SMALL BOWEL NEUROENDOCRINE TUMORS. Nih.gov; Zuckschwerdt. https://www.ncbi.nlm.nih.gov/books/NBK6976/
[3]Gomes, C. T. de O., Luz, P. F. N. da, Costa, G. D. de F., Grangeiro, J. S., Jeronimo, H. L. C., Pereira, L. M. M. B., Vasconcelos, G. B. S. de, & Mello Filho, R. M. de. (2015). DOENÇA DE CROHN ASSOCIADA A TUMOR CARCINOIDE GÁSTRICO: RELATO DE CASO E REVISÃO DE LITERATURA. GED Gastroenterol. Endosc. Dig., 35(4), 162–165. https://docs.bvsalud.org/biblioref/2017/03/832654/doenca-de-crohn-associada.pdf

Disclosure

Illustrative material will be used in the poster, including colonoscopy images, enterotomography, and photographs of the resected surgical segment. The authors of this study declare, for all intents and purposes, that they have no Conflict of Interest regarding the subject of this research.

Introduction

Intestinal ultrasound (IUS) is a non-invasive, reproducible, low-cost technique for the assessment of intestinal diseases.¹
Crohn's disease (CD) and irritable bowel syndrome (IBS) are two of the major causes of chronic diarrhoea and abdominal pain in high-income countries.² IBS, especially in the diarrheal (IBS-D) or mixed (IBS-M) variants, has clinical features similar to those of CD.
The role of IUS in the diagnosis and monitoring of CD is well established,^{3, 4} whereas only scanty data are available on IBS. Current IBS guidelines do not recommend the use of IUS even to distinguish between IBS-D or IBS-M and CD.^{5, 6}

Aims & Methods

The aim of this two-gate diagnostic study was to assess the accuracy of IUS in discriminating between IBS-D or IBS-M and CD in patients presenting with similar symptoms.
In a high-volume tertiary Centre, consecutive patients symptomatic for chronic diarrhoea and abdominal pain underwent IUS performed by three experienced gastroenterologists.
In the group with clinically active CD, patients had a previous diagnosis based on clinical, biochemical, endoscopic, radiologic and histologic criteria, while in the IBS group subjects had a previous diagnosis based on Rome IV Criteria.
Bowel wall thickness (BWT) of the terminal ileum, ascending colon, transverse colon and descending colon/sigma was evaluated using two cut-offs of 3 mm and 4 mm.⁷ Enlarged lymph nodes, mesenteric fat hypertrophy, bowel wall stratification and submucosal vascularity were also assessed.
The diagnostic accuracy of IUS in discriminating between the two groups was estimated in terms of sensitivity, specificity, positive and negative likelihood ratios (LR+ and LR-) and overall accuracy (OA) (Table 1).

Results

A total of 50 patients with IBS (62% female, mean age 41 years, SD ± 13 years, 54% IBS-D) and 50 subjects with CD (44% female, mean age 47 years, SD ± 17 years) were enrolled.
Forty-nine patients with IBS (98%) and 8 patients with CD (16%) and had a BWT < 3 mm. 49 patient with IBS (98%) and 12 patients with CD (24%) had a BWT < 4 mm.
Sensibility, specificity, LR+ and LR- of BWT < 3 mm were 98%, 84%, 6.13 and 0.02, respectively.
Sensibility, specificity, LR+ and LR- of BWT < 4 mm were 98%, 76%, 4.08 and 0.03, respectively.
BWT with 3 mm and 4 mm cut-offs showed an OA in discriminating between CD and IBS-D or IBS-M of 91% and 87%.
The absence of altered IUS parameters had 94% OA in discriminating between CD and IBS (Table 1).

Conclusion

IUS seems able to discriminate between IBS-D or IBS-M and CD in patients with chronic diarrhoea and abdominal pain. Particularly, a BWT < 3 mm may rule out the presence of clinically active CD and support the diagnosis of IBS. On the other hand, a BWT > 3 mm or a single altered ultrasound parameter might raise suspicion of CD and justify further testing. Cross-sectional studies are needed to confirm these preliminary results.

References

[1] Bryant RV, et al. Gastrointestinal ultrasound in inflammatory bowel disease: an underused resource with potential paradigm-changing application. Gut 2018;67(May (5)):973–85.
[2] Arasaradnam TP, et al. Guidelines for the investigation of chronic diarrhoea in adults: British Society of Gastroenterology, 3rd edition. Gut vol. 67,8 (2018): 1380-1399.
[3] Castiglione F, et al. Noninvasive diagnosis of small bowel Crohn’s disease: direct comparison of bowel sonography and magnetic resonance enterography. Inflamm Bowel Dis 2013;19:991–8.
[4] Maaser C et al. ECCO-ESGAR Guideline for Diagnostic Assessment in IBD Part 1: Initial diagnosis, monitoring of known IBD, detection of complications. Journal of Crohn's & colitis vol. 13,2 (2019): 144-164.
[5] Vasant, Dipesh H et al. British Society of Gastroenterology guidelines on the management of irritable bowel syndrome. Gut vol. 70,7 (2021): 1214-1240.
[6] Savarino E et al. “Functional bowel disorders with diarrhoea: Clinical guidelines of the United European Gastroenterology and European Society for Neurogastroenterology and Motility.” United European gastroenterology journal vol. 10,6 (2022): 556-584.
[7] Fraquelli M, et al. Role of US in detection of Crohn disease: meta-analysis. Radiology. 2005;236(1):95-101.

Introduction

Adalimumabe (ADA) 160/80 mg is efficacious for induction of clinical remission in patients with intestinal Crohn’s disease (CD), but data on its long-term efficacy for perianal CD are more limited.

Aims & Methods

To determine whether treatment with Adalimumab is effectiveness in patients with perianal CD. A prospective randomized study , from January 2019 until January 2023 was enrolled with 100 patients (38f/62m, mean age 41, 15 smokers). The patients presented ( trans or suprasphinteric, horse-shoes, multiple with or without rectal involvement), perianal fistulising disease or resistant to immunosuppressive. All patients received 160/80 mg of Adalimumab as induction dose. Immunosupressive therapy was suspended at the start of treatment and steroid dose was reduced of 5 mg/week after the induction phase. The study was performed in a reference public/medical school hospital in Porto Velho, north region of Brazil
Definition of remission: complete closure of the fistula assessed with colonoscopy and magnetic resonance imaging ( MRI ).

Results

Medical charts of 100 patients with perianal CD receiving Adalimumab were investigated. Among them, 42 had infliximab failure, 67/100 colonic disease, 82/100 rectal involvement, 42/100 were also using steroid. At week 6, 18/100 patients (18%), were in remission; at week 30, 29/100 patients (29%) were in remission; at week 52, 66/100 (66%), were in remission and at 3 years, 77/96 patients (80%) were in remission. 4 patients loss response and moved to a temporary loop-ileostomy. No serious adverse events were registered.

Conclusion

Adalimumabe treatment was effective in the remission of perianal CD in 80% of the patients after a 4 years follow-up, showing the effectiveness of adalimumabe.

References

- Hanauer S.B. Sandborn W.J. Rutgeerts P. Fedorak R.N. Lukas M. MacIntosh D. et al. Human anti-tumor necrosis factor monoclonal antibody (adalimumab) in Crohn's disease: the CLASSIC-I trial Gastroenterology 130 2006 323 - 333
- Sandborn W.J. Hanauer S.B. Rutgeerts P. Fedorak R.N. Lukas M. MacIntosh D.G. et al. Adalimumab for maintenance treatment of Crohn's disease: results of the CLASSIC II trial Gut 56 2007 1232 123
- Colombel J.F. Sandborn W.J. Rutgeerts P. Enns R. Hanauer S.B. Panaccione R. et al. Adalimumab for maintenance of clinical response and remission in patients with Crohn's disease: the CHARM trial Gastroenterology 132 2007 52 - 65