Endoscopic insights into digestive-related adverse effects of immune checkpoint inhibitors: A narrative review

Table 1 Classification of upper gastrointestinal symptom severity according to the Common Terminology Criteria for Adverse Events

Condition	Grade 1	Grade 2	Grade 3	Grade 4	Grade 5
Abdominal pain	Mild pain	Moderate pain; Limiting instrumental ADL	Severe pain; Limiting self-care ADL
Dysphagia	Symptomatic, able to eat a regular diet	Symptomatic and altered eating or swallowing	Severely altered eating/swallowing; Tube feeding, TPN, or hospitalization indicated	Life-threatening consequences; Urgent intervention indicated	Death
Vomiting	Intervention not indicated	Outpatient IV hydration; Medical intervention indicated	Tube feeding, TPN, or hospitalization indicated	Life-threatening consequences	Death
Upper GI hemorrhage	Mild symptoms; Intervention not indicated	Moderate symptoms; Intervention indicated	Transfusion indicated; Invasive intervention indicated; Hospitalization	Life-threatening consequences; Urgent intervention indicated	Death

GI: Gastrointestinal; ADL: Activities of daily living; IV: Intravenous; TPN: Total parenteral nutrition.

Table 2 Classification of lower gastrointestinal symptom severity according to the Common Terminology Criteria for Adverse Events

Condition	Grade 1	Grade 2	Grade 3	Grade 4	Grade 5
Anal pain	Mild pain	Moderate pain; Limiting instrumental ADL	Severe pain; Limiting self-care ADL
Colitis	Asymptomatic; Clinical or diagnostic observations only; Intervention not indicated	Abdominal pain; Mucus or blood in stool	Severe abdominal pain; Peritoneal signs	Life-threatening consequences; Urgent intervention indicated	Death
Diarrhea	Increase of < 4 stools per day over baseline; Mild increase in ostomy output compared to baseline	Increase of 4-6 stools per day over baseline; Moderate increase in ostomy output; Limiting instrumental ADL	Increase of ≥ 7 stools per day over baseline; Hospitalization indicated; Severe increase in ostomy output; Limiting self-care ADL	Life-threatening consequences; Urgent intervention indicated	Death
Upper GI hemorrhage	Mild symptoms; Intervention not indicated	Moderate symptoms; Intervention indicated	Transfusion indicated; Invasive intervention indicated; Hospitalization	Life-threatening consequences; Urgent intervention indicated	Death

GI: Gastrointestinal; ADL: Activities of daily living.

Table 3 Histopathological characteristics of inflammatory patterns in biopsies from patients with immune checkpoint inhibitor-associated colitis

Histopathological pattern	Histopathological features
Active inflammation	Neutrophil epithelial infiltration, cryptitis, crypt abscess formation, with or without mixed-cell infiltration of the lamina propria
Chronic active inflammation	Basal lymphoplasmacytosis, crypt architectural distortion, paneth cell metaplasia, cryptitis and/or crypt abscess formation
Microscopic colitis	Lymphocytic type with lymphocytic epithelial infiltration, lymphoplasmacytic lamina propria expansion or collagenous type with thickened subepithelial collagen layer
Mixed type	Combined features from the aforementioned categories