A 69-year-old man with a 1-month history of right chest pain, cough, and expectoration had undergone an X-ray of the chest at the outpatient clinic of the Shanghai Tenth People's Hospital of Tongji University (Shanghai, China) on October 23, 2021. Chest X-ray examination showed a high-density mass in the middle lobe of the right lung ( Figure 1A ). Further CT-guided percutaneous lung biopsy of these lung nodules was performed on November 10, 2021. One week later, biopsy pathology revealed CK7(+), TIF-1(+), SYN(+), CD56(+), and ki-67 (60% +), confirming that it was poorly differentiated neuroendocrine carcinoma (SCLC) ( Figures 1B, D-K ). What was worse, PET-CT showed that he had pleural, mediastinal lymph node, and cerebellar metastases. Brain MRI confirmed metastasis of lung cancer in the cerebellar tonsillar ( Figure 1C ).
Thus, the patient was admitted to the Department of Oncology in our hospital on November 15, 2021. He was a non-drinker and non-smoker, and had tuberculosis 50 years ago, which had been cured already. In addition, he had no history of any other diseases like gastrointestinal diseases and autoimmune diseases or medication use such as non-steroidal anti-inflammatory drugs (NSAIDs), proton pump inhibitors, or probiotics. He also denied any family history of hypertension, diabetes, and tumor. On admission, he had experienced a weight loss of 5 kg in 4 months and gradually worsening right chest pain, cough, and expectoration despite that he had taken an antibiotic (i.e., amoxil capsule) since 1 week ago. His Karnofsky performance score (KPS) was 80, and his body mass index (BMI) was 19.37. Physical examination was almost negative except for mild coarse breath sounds of both lungs on auscultation. Laboratory tests revealed significant increases in carcinoembryonic antigen (CEA; 7.90 ng/ml; n.v., <5.2 ng/ml), carbohydrate antigen (CA)-153 (27.10 U/ml, n.v., <26.4 U/ml), CA-125 (104 U/ml; n.v., <35 U/ml), and neuron-specific enolase (NSE; 32 ng/ml; n.v., <16.3 ng/ml); but C-reactive protein (CRP; 3.30 mg/L; normal value (n.v.), <8.2 mg/L), white blood cell (WBC; 8.56 x 10(9)/L; n.v., 3.5-9.5 x 109/L), red blood cell (RBC, 4.29 x 1012/L; n.v., 4.3-5.8 x 1012/L), platelet (PLT; 439 x 109/L; n.v., 125-350 x 109/L), and hemoglobin (Hb; 138 g/L; n.v., 130-175 g/L), serum albumin (ALB, 37.3 g/L; n.v., 35-50 g/L), hepatic and renal functions, bleeding time test, D-dimer (0.50 mg/L; n.v., <0.55 mg/L FEU), and fecal tests were almost normal ( Table 1 ). Considering that his KPS and BMI are relatively low within normal limits, his oncologist recommended a regimen of anti-PD-L1+IP, namely, durvalumab, a PD-L1 antibody, intravenous injection on the 1st day and irinotecan and cisplatin intravenous injection on the 1st and 8th days, allowing for the evaluation of his tolerance to chemotherapy after the first injection. After informed consent was acquired, durvalumab (1,500 mg; Imfinzi; AstraZeneca, Cambridge, UK) was administered to the patient together with irinotecan (115 mg, Pfizer, Manhattan, NY, USA) and cisplatin (50 mg, Teva Pharma AG, Basel, Switzerland) on November 16, 2021 (1st day). No adverse reaction was reported by him in the next 1 week. No obvious change was found in his laboratory test 1 week later, except for a slight increase of D-dimer (0.95 mg/L) ( Table 1 ). Therefore, he received irinotecan and cisplatin of the same dosage as mentioned above on November 23, 2021 (8th day). Later, he presented mild diarrhea (2-3 times/day, grade I) for three days. His oncologist considered it was chemotherapy-induced diarrhea and prescribed him antidiarrheal medicine in an outpatient clinic. However, he developed moderate diarrhea 5-6 times/day and mild abdominal pain (grade II) afterward, even though he had taken antidiarrheal medicine daily at home. Thus, he had to be hospitalized again in the Department of Oncology in our hospital on November 29, 2021. In this instance, laboratory tests revealed significant increases in CRP (59.77 mg/L). As shown in  Table 1 , ALB (33.1 g/L), WBC (1.76 x 109/L), RBC (3.98 x 1012/L), and Hb (121 g/L) were significantly decreased. Routine fecal test (RFT) and fecal occult blood test (FOBT) were still negative, as well as fecal ova/parasites tests, stool pathogen cultures, and Clostridium difficile toxin tests. In addition, serum coagulation function tests were revealed to be normal, but D-dimer increased significantly (>20.3 mg/L). Further CT angiography excluded mesenteric embolism or bowel perforation.
His symptoms worsened with bloody diarrhea (6-10 times/day) and moderate abdominal pain (grade III). FOBT became positive (++), but no RBC or WBC was found in RFT. In order to obtain special therapy, he was transferred to the Department of Gastroenterology on December 1, 2021. No evidence of vasculitis, fungal elements, tuberculosis, viral staining for cytomegalovirus, Epstein-Barr virus (EBV)- encoded RNA (EBER), adenovirus, or parasitic infection was found in further laboratory tests. Therefore, the patient was diagnosed with ICI-induced colitis and started on 120 mg of intravenous methylprednisolone daily on December 2, 2021. Three days later, he developed more severe bloody diarrhea (>15 times/day) and moderate-to-severe abdominal pain (grade III), and his ALB decreased significantly. Subsequent colonoscopy showed severe mucosal inflammation from the transverse colon to the anus with multiple ulcerations attached with purulent secretions and moss, consistent with Mayo endoscopic subscore of 3 ( Figures 2A-D ). No obvious abnormality was found in the gastroscope. Histopathological analysis of colon biopsies revealed that there was multiple purulent exudation and necrosis, and colonic crypt atrophy or rupture, suggestive of acute enteritis ( Figures 2E-H ). Considering that he was steroid refractory, 5 mg/kg of anti-TNF mAb (i.e., infliximab; Cilag AG, Schaffhausen, Switzerland) was administered to him on December 4, 2021, followed by a reduced dose of methylprednisolone (60 mg/day) intravenously daily for another 4 days. Meanwhile, enteral nutrition, albumin infusion, empiric antibiotic therapy, and oral probiotics were administered to him daily, and hemostatic therapy was administered to him intermittently when needed. Unexpectedly, his bloody diarrhea became more severe (>20 times/day), and abdominal pain worsened. We immediately switched to total parenteral nutrition on December 7, 2021, and 300 mg of anti-integrin mAb (i.e., vedolizumab; Takeda GmbH, Konstanz, Germany) was administered to the patient to strengthen immunosuppression on December 11, 2021 ( Figure 3 ). At this time, laboratory findings reflected the patient's clinical degradation, including CRP 191 mg/L, ALB 18.9 g/L, and Hb 49 g/L, as shown in  Table 1 . He was urgently treated with fluid resuscitation and blood transfusions on December 11 and 12, 2021, respectively. Furthermore, 300 mg of infliximab was administered to him in advance in order to save him from severe colitis. Unfortunately, he died on December 13, 2021, due to severe lower gastrointestinal bleeding and hemorrhagic shock.