Introduction

Patients with inflammatory bowel disease (IBD) in clinical and endoscopic remission may still experience disease relapse. Therefore, there is an unmet need for reliable predictors of outcomes to enable a personalized therapeutic approach. Recently, a novel histological score has highlighted the pivotal role of neutrophils in predicting disease outcomes in Ulcerative Colitis (UC)¹. Furthermore, the impairment of the intestinal barrier plays a key role in forecasting disease outcomes in UC and Crohn’s disease (CD). Hence, this study aims to assess the predictive role of neutrophils according to their tissue localization and intestinal barrier protein expression in IBD patients.

Aims & Methods

IBD patients in clinical remission who underwent colonoscopy between January 2020 and June 2022 at two tertiary referral centres were enrolled. Patients with a Mayo Endoscopic Score ≤1 for UC and a Simple endoscopic score of ≤6 for CD were included. The histological activity was assessed using the Robarts Histopathology Index, Nancy Histological Index, and PICaSSO Histological Remission Index. Neutrophil localization in the epithelium and lamina propria was carefully evaluated by experienced pathologists. Additionally, the immunohistochemical expression of barrier proteins, such as Claudin-2 and JAM (junctional adhesion molecule)-A, was assessed to evaluate the integrity of the intestinal barrier.

Results

Out of 60 UC and 76 CD patients, 60% were in histological activity. 25.8% of patients developed an adverse outcome within 12 months. Only neutrophils in the epithelium and not in lamina propria could predict adverse outcomes for UC (HR 5.20, p=.01) and CD (HR 4.38, p=.03) patients in endoscopic remission. Moreover, epithelial Claudin-2 expression correlated with endoscopic and histological disease activity and predicted outcomes in UC. Combining neutrophils in the epithelium or Claudin-2 expression significantly predicted outcomes in UC patients (HR 3.23, p=.035). Similar results were found for JAM-A in CD despite this protein showing less specificity as a barrier predictor of outcome.

Conclusion

This multicentre study highlights the potential role of epithelial neutrophil localization and Claudin-2 ‘leaky gut’ protein expression as practical clinical tools for predicting outcomes in IBD and potentially guiding patient-tailored therapy.

References

¹Gui X et al., Gut. 2022;71(5):889-898.

Disclosure

None

Clinical Case Summary

A 62-year-old female, followed for hypothyroidism and is receiving Levothyroxine at a dosage of 100 µg daily, with a prior surgical removal of a subcutaneous lipoma located on the dorsal region, presented with isolated persistent postprandial vomiting over the past four months. Physical examination revealed mild dehydration; the abdomen was soft with no palpable mass. Laboratory tests showed a hypercalcemia, no other abnormalities were noted.
Gastroscopy revealed an erythematous gastric mucosa and a mass protruding into the antrum with normal overlying mucosa and a yellow hue; a sponge-like sinking impression was observed as the biopsy forceps was gently pushed into the lesion. Systematic gastric biopsies revealed a chronic nonspecific gastritis, the mass was not biopsied. An abdominal computed tomography (CT) scan depicted a gastric homogenous low-density mass of fatty tissue and three intramuscular masses with the same characteristics in the thigh, the largest measuring 5cm. the CT scan also revealed a suspicious osteolytic lesion of the iliac crest. An endoscopic ultrasound (EUS) showed a hypoechoic well-defined mass arising from the third parietal layer consistent with a lipoma. A thigh magnetic resonance imaging (MRI) revealed intramuscular lesions with the circumscribed, low attenuation mass compatible with lipomas. A biopsy of the osteolytic lesion revealed a multiple myeloma. The patient is scheduled to receive chemotherapy for the multiple myeloma as for the lipomas, no treatment was warranted.

Clinical Case Summary

About 1-2% of pancreatic tumors are neuroendocrine pancreatic tumors (NETs). They are often solid masses; rarely they appear as cystic lesions.
The authors report the clinical case of a 66-year-old woman with unspecific abdominal pain, who was referred to the Pancreato-biliary clinic for pancreatic cystic lesions. Magnetic resonance cholangiopancreatography and abdominal CT showed multiple cystic lesions in the distal body and a lesion of 26 mm in the anterior region of the body with diffusion restriction; the duct of Wirsung was dilated (8 mm). Endoscopy ultrasound showed: several hyperechoic foci in the pancreatic parenchyma; a nodular hyperechoic lesion measuring 9 mm in the pancreatic body; a cystic lesion measuring 6 mm in the body; and two cystic lesions measuring 38 and 25 mm in the tail. Fine needle biopsy of the nodular lesion and fine needle aspiration of the larger cystic lesions was performed; the aspiration punction showed amylase 33207 U/L and carcinoembryonic antigen 0.9 ng/mL; however, the cytology of both lesions was inconclusive. Somatostatin receptor scintigraphy showed uptake in the pancreatic body's anterior region and high somatostatin receptor expression, suggesting a neuroendocrine pancreatic tumor diagnosis. In the multidisciplinary team discussion, the decision was to perform total duodenopancreatectomy with splenectomy, which occurred without complications. Histological examination revealed several well-differentiated NETs, the largest of which measured 4 cm, with < 2 mitoses per 2 mm², a proliferation index of 3-20% and regional ganglionic metastasis (pT3(m)N1). At 2 years of follow-up, the patient remains clinically stable without evidence of recurrence of the disease.
This case report, while displaying remarkable images, intends to highlight the challenge of the differential diagnosis between cystic lesions and neuroendocrine tumors of the pancreas; both entities can coexist synchronously and they may share imagiological features.

References

Images list:

1. Multiple cystic pancreatic lesions and a pancreatic lesion in the anterior region of the body with diffusion restriction (Magnetic Resonance Cholangiopancreatography).
2. Multiple cystic lesions in the distal body and a pancreatic lesion in the anterior region of the body (Abdominal Computed Tomography).
3. Several hiperecoic foci in the pancreatic parenchyma; a nodular hiperecoic lesion measuring 9 mm in the pancreatic body; a cystic lesion measuring 6 mm in the body; and two cystic lesions measuring 38 and 25 mm in the tail (Endoscopy ultrasound).
4. Uptake in the pancreatic body's anterior region and high somatostatin receptor expression (Somatostatin receptor scintigraphy)