Peptic ulcer induced by immune checkpoint inhibitors successfully treated with glucocorticoids: A report of three cases and a literature review

Abstract

In recent decades, immune checkpoint inhibitors (ICIs) have emerged as safer and less disruptive alternatives to conventional chemotherapy and radiotherapy for certain patients with tumours. ICIs serve a synergistic role alongside conventional therapies by manipulating the immune system to recognise and target tumour cells. However, excessive activation of the immune system can lead to immune-related adverse events including pneumonia, myocarditis and colitis, which pose serious and even fatal risks. In the present case series, three patients with a thoracic tumour with an ICI-induced peptic ulcer triggered by programmed cell death protein 1 antibodies (diagnosed by gastrointestinal endoscopy) are presented. These cases were successfully treated with corticosteroids. The diagnostic and treatment processes undertaken for these patients underscore the requirement to comprehensively understand the mechanism of ICI-induced peptic ulcer. Moreover, the relevant literature was also reviewed in the present study.

Keywords: ICI-induced peptic ulcer; adverse effects; immune checkpoint inhibitor; immunotherapy; thoracic tumours.

Figure 1

Contrast-enhanced CT of the chest of patient 1. CT from the first physical examination (A, October 2018) and of the mediastinal metastasis (B, November 2019), liver metastasis (C, August 2020) and sternal metastases (D, November 2020).

Figure 2

H&E staining (magnification, x200) of tumor tissue of right lung from patient 1.

Figure 3

Gastrointestinal endoscope images of patient 1. (A) A large duodenal bulbar ulcer before administration of methylprednisolone and omeprazole. (B) The regression of the duodenal bulbar ulcer to ~0.3 cm in diameter after administrations of methylprednisolone and omeprazole. (C) A new duodenal bulbar ulcer (1.2 cm) next to the scar tissue of the previous ulcer, after re-administration of tislelizumab. (D) Regression of the new ulcer with scaring and erythema after the second administration of tislelizumab.

Figure 4

H&E staining (magnification, x200) of tumor tissue of lymph node from patient 2.

Figure 5

Contrast-enhanced CT of patient 2. CT images of (A) mediastinal mass and (B) lung metastasis. (C) A pulmonary image before treatment for ICI-related pneumonia. (D) A pulmonary image after treatment for ICI-related pneumonia. ICI, immune checkpoint inhibitor.

Figure 6

Gastrointestinal endoscope images of patient 2. (A and B) The large duodenal bulbar ulcer with friability. (C and D) Regression of the duodenal bulbar ulcer.

Figure 7

Contrast-enhanced CT of the chest of patient 3. CT images of the (A) left and (B) right lungs.

Figure 8

H&E staining (magnification, x200) of patient 3. Tissues from the (A) left and (B) right lungs.

Figure 9

GI endoscopy images of patient 3. (A and B) GI endoscope images of the gastric antrum with redness and multiple ulcers covered with white moss. (C and D) The healing of multiple ulcers after the administration of dexamethasone. GI, gastrointestinal.