A 54-year-old male was diagnosed as having lung cancer. He underwent video-assisted thoracoscopic surgery for left upper lung cancer in the Second Affiliated Hospital of the University of South China, and his postoperative diagnosis was polymorphic adenocarcinoma of the left upper lung (T2aN2M0 stage IIIA). Immunohistochemical staining showed the following: CK (+), CK7 (+), TTF1 (+), Napsin A (part+), Vim (+), Syn (-), CgA (-), CD56 (-), P40 (-), CK5/6 (-), and Ki67 (50%+). After the surgery, he was started on the TP chemotherapy regimen, which included the administration of carboplatin (40 mg, days 1-3) + paclitaxel (400 mg, day 1). Four cycles of this TP chemotherapy regimen were administered, with each cycle lasting about 21 days. However, about 178 days postoperatively, he was diagnosed with brain metastases [pT2N2M1 stage IV, epidermal growth factor receptor/anaplastic large-cell lymphoma kinase/ROS1 negative, Kirsten rat sarcoma virus (KRAS) mutation 71.8%, KRAS amplification 2.4, cyclin D1 gene amplification 2.6, cyclin-dependent kinase inhibitor 2A mutation 9.1%, and PD-L1 tumor proportion score 60%], after which he received eight courses (approximately 21 days per course) of bevacizumab (1,100 mg) + sintilimab (200 mg) from 2020 to 2021. In April 2021, he was started on sintilimab maintenance therapy. Bevacizumab was discontinued. About 10 days later, he soon visited our hospital for epigastric pain. He underwent gastroscopy on day 419, which showed squamocolumnar junction (SCJ) blurred, local mucosal hyperemia edema with erosion and opaque white mucus covering the mucosal surface, and localized hemorrhage. A large amount of opaque white mucus was attached to the mucosal surface of the gastric antrum and body, and the gastric mucosa was diffusely hyperemic with spontaneous hemorrhage ( Supplementary Figure 1). Colonoscopy showed no abnormalities. The patient was treated with oral ilaprazole (5 mg, once daily) and gastric protection with sucralfate oral suspension (1 packet, twice daily). Repeat esophagogastroduodenoscopy (EGD) performed in May showed improvements, and repeat colonoscopy still showed no abnormalities. Then, he stopped the oral drug treatment without permission from the doctors after the symptoms subsided ( Supplementary Figure 2).
After treatment with three courses of sintilimab alone, he had recurrent epigastric pain and black tarry stools, which were worse than before. Repeat EGD showed that the entire gastric mucosa was evidently edematous and hyperemic and showed adhesion of opaque mucus, diffuse erosion of the white moss, and active localized hemorrhaging was extensively observed. The gastric antrum was found to have a necrotic mucosa with exfoliation of large flakes ( Figure 1 ). The Carbon 14 breath test was negative, and tests for cytomegalovirus and Epstein-Barr virus revealed a previous infection, but not a current infection. The patient was also negative for tuberculosis immunoglobulin G (IgG) antibodies, HBV, HCV, syphilis antibodies, and HIV ( Supplementary Table 1 ). Initially, he was treated with esomeprazole (40 mg every 6 h via an intravenous pump), oral rebamipide (100 mg, thrice daily), sucralfate oral suspension (10 ml, twice daily), and rehabilitative new liquid (10 ml, thrice daily, taken orally). However, the symptoms of the patient did not subside and were aggravated even with consuming a small amount of water or other fluids. After regular treatment for acute erosive hemorrhagic gastritis, his fecal occult blood test was still positive, indicating that the upper GI lesion still existed.
After three days of the abovementioned regular treatment for acute gastritis, his EGD revealed that the whole gastric mucosa was hyperemic and edematous, with erosion of the attached diffuse white moss and active oozing of blood. Small flaps of mucosal necrosis and stripping could be visualized at the posterior wall of the gastric antrum, indicating a relatively healed mucosa compared with previous EGD findings ( Figure 2 ). Pathologic findings of the biopsy specimens from the gastric antrum showed severe atrophic gastritis with erosion, atrophy, and loss of intrinsic glands; focal aggregation of lymphocytes in the lamina propria and mucosal muscular layer; multiple neutrophil infiltration; and the formation of small abscesses ( Figure 3 ). Considering that bevacizumab has already been discontinued for almost 2 months, it can be concluded that the current presentation was not an effect of bevacizumab; we confirmed that his gastritis was associated with the immune checkpoint inhibitor sintilimab.
We suspended sintilimab administration and simultaneously changed the regimen to steroid therapy as follows: intravenous methylprednisolone sodium succinate drip (100 mg, once daily for 4 days; 70 mg, once daily for 3 days; and 40 mg, once daily for 3 days), followed by oral methylprednisolone tablets as maintenance therapy (32 mg once daily for a week;  Supplementary    Figure 3 ). His symptoms gradually subsided after this treatment. Re-examination of EGD on day 526 showed markedly relieved edematous and hyperemic gastric mucosa and no signs of active oozing of blood compared to previous EGD findings ( Figure 4 ). The patient began to resume the next course of sintilimab treatment (200 mg, 42 days per cycle) starting in October (day 598). Approximately half a month later (day 613), his EGD revealed that the entire gastric mucosa was hyperemic and edematous with white opaque mucus attachment; however, no erosion, ulcer, or mass was identified ( Supplementary Figure 5 ).