# Start Early and See Inflammatory; Late, Nothing Save RAVE: How to Appreciate Radiation Proctitis as a Continuum

## TL;DR

The paper argues that inflammation plays a key role in the development of radiation proctitis, suggesting it should be viewed as a continuum rather than a single condition.

## Contribution

The paper introduces new evidence that inflammation initiates radiation proctitis, challenging the proposed name change to a purely vascular condition.

## Key findings

- VEGF and CEACAM1 expression is elevated before radiotherapy and declines over time.
- p38 MAP kinase expression typically precedes radiation exposure.
- Fibrosis increases while vascular scores decrease over time, suggesting a progression from inflammation to vascular changes.

## Abstract

It has been recently proposed to change the nomenclature of “chronic radiation proctitis” (CRP) to “radiation-associated vascular ectasia” on the basis that signs of inflammation are rarely observed. We herein present data supporting the idea that inflammation is a critical step that initiates the process that culminates in the characteristic changes of CRP.

In support of inflammation in the pathogenesis of CRP, we review the pertinent literature and publish our new results, including the role of amifostine treatment and proinflammatory factors (p38 MAP kinase, VEGF, and CEACAM1).

Immunohistochemistry from anterior rectal wall biopsies obtained in a prospective pilot study demonstrates that expression of VEGF and the downstream vascular effector CEACAM1 were elevated before radiotherapy and declined with time. We also show that MAP Kinase p38 expression usually precede the radiation. Fibrosis scores increase from baseline at 9 and 18 months, while vascular scores decrease at 18 months.

The proposed new nomenclature should be held in obeyance until more supportive data are presented. Possibly, the best way to view CRP is as a continuum that may take one of three forms, inflammation-predominant, vasculopathy-predominant, or mixed.