Gastro-intestinal toxicity of chemotherapeutics in colorectal cancer:The role of inflammation

Chemotherapy-induced diarrhea(CID)is a common and often severe side effect experienced by colorectal cancer(CRC)patients during their treatment.As chemotherapy regimens evolve to include more efficacious agents,CID is increasingly becoming a major cause of dose limiting toxicity and merits further investigation.Inflammation is a key factor behind gastrointestinal(GI)toxicity of chemotherapy.Different chemotherapeutic agents activate a diverse range of pro-inflammatory pathways culminating in distinct histopathological changes in the small intestine and colonic mucosa.Here we review the current understanding of the mechanisms behind GI toxicity and the mucositis associated with systemic treatment of CRC.Insights into the inflammatory response activated during this process gained from various models of GI toxicity are discussed.The inflammatory processes contributing to the GI toxicity of chemotherapeutic agents are increasingly being recognised as having an important role in the development of anti-tumor immunity,thus conferring added benefit against tumor recurrence and improving patient survival.We review the basic mechanisms involved in the promotion of immunogenic cell death and its relevance in the treatment of colorectal cancer.Finally,the impact of CID on patient outcomes and therapeutic strategies to prevent or minimise the effect of GI toxicity and mucositis are discussed.

Controversies in the pathological assessment of colorectal cancer

Pathologic assessment of colorectal cancer specimens plays an essential role in patient management,informing prognosis and contributing to therapeutic decision making.The tumor-node-metastasis(TNM)staging system is a key component of the colorectal cancer pathology report and provides important prognostic information.However there is significant variation in outcome of patients within the same tumor stage.Many other histological features such as tumor budding,vascular invasion,perineural invasion,tumor grade and rectal tumor regression grade that may be of prognostic value are not part of TNM staging.Assessment of extramural tumor deposits and peritoneal involvement contributes to TNM staging but there are some difficulties with the definition of both of these features.Controversies in colorectal cancer pathology reporting include the subjective nature of some of the elements assessed,poor reporting rates and reproducibility and the need for standardized examination protocols and reporting.Molecular pathology is becoming increasingly important in prognostication and prediction of response to targeted therapies but accurate morphology still has a key role to play in colorectal cancer pathology reporting.

Endoscopic evaluation in diagnosis and management of inflammatory bowel disease

Endoscopy is a keystone in the management of patients with inflammatory bowel disease (IBD). It is the fundamental diagnostic tool for IBD, and can help discern between ulcerative colitis and Crohn’s disease. Endoscopic assessment provides an objective end point in clinical trials, and identifies patients in clinical practice who may benefit from treatment escalation and may assist risk stratification in patients seeking to discontinue therapy. Recent advances in endoscopic assessment of patients with IBD include video capsule endoscopy, and chromoendoscopy. Technological advances enable improved visualization and focused biopsy sampling. Endoscopic resection and close surveillance of dysplastic lesions where feasible is recommended instead of prophylactic colectomy.