Proctitis

 

Clinical Background

Radiation-induced proctitis is a common complication associated with radiation directed to the abdomen and/or pelvis in the treatment of rectal, prostate, or cervical malignancies. The symptoms of proctitis can begin as early as immediately following therapy (acute) or as late as well after completion of radiation therapy (delayed or late). Acute proctitis symptoms can persist up to 3 months, while delayed or late proctitis is a chronic disease that may continue for decades. Proctitis symptoms include rectal bleeding, diarrhea, discharge of mucus and tenesmus, a feeling or inability to empty the bowel upon defecation, which is likely a result of extensive rectal tissue fibrosis or possibly the formation of rectal strictures.
The most common first-line therapies have been adapted from the treatments used in inflammatory bowel disease (IBD), including 5-ASA, steroids, sucralfate and metronidazole. Increasingly, endoscopic therapies are being employed to control bleeding associated with radiation proctitis which includes heat probes, lasers, and most commonly argon plasma coagulation (APC). Unfortunately, current treatment options for radiation proctitis vary as greatly in their rate of success as they do in method.

Preclinical Models

Model Description Length Endpoints
Acute Radiation- Induced Proctitis
Disease is evident at day 3, peaks near day 7 and persists through the final evaluation. 10 days Endoscopy score, weight, incidence of diarrhea, histology
Fractionated Radiation- Induced Proctitis
Disease is evident the day after the final dose of radiation. Severity peaks on day 13 and persists through the final evaluation. 28 days Endoscopy, score, weight, incidence of diarrhea, histology

 

Radiation-Induced Proctitis

Biomodels offers both acute and fractionated rat and mouse models of radiation-induced proctitis. In both models, lead shielding is used to cover the rat except for a 3cm X 4cm area of the low pelvis. This area contains approximately a 2 cm length of the rectum and distal colon in the middle of the field. The peak of disease severity differs between the acute and fractionated models. End points in this model include endoscopic proctitis scores based on a standardized scale that is representative of the clinical assessment, combined with weight, incidence of diarrhea and histological analysis.

Acute Radiation-Induced Proctitis

Animals receive one acute dose of radiation on Day 0 of the study and then are evaluated daily
for survival, body weight, evidence of bloody stool and diarrhea. On three of those days, animals are anesthetized and examined via video endoscopy to determine proctitis severity.

Study Design

 

 

*Proctitis severity scores resulting from acute radiation exposure

 

Fractionated Radiation-Induced Proctitis

Animals receive 8 fractionated doses of radiation on days 0, 1, 2, 3, 6, 7, 8, and 9 of the study.

Study Design

 

Mean Radiation Induced Proctitis Scores

proctitis_graph_2

*Proctitis severity scores resulting from fractionated radiation exposure

 

Endoscopy Proctitis Images

 

Photomicrograph showing histological appearance of normal rectal mucosa.

Photomicrograph showing histological appearance of normal rectal mucosa.

Photomicrograph showing histological appearance of inflamed rectal mucosa.

Photomicrograph showing histological appearance of inflamed rectal mucosa.

 

Publications

Animal models of toxicities caused by anti-neoplastic therapy
Stephen T. Sonis, Gregory Lyng, and Kimberly Pouliot
Tumor Models in Cancer Research, second edition, Beverly A. Teicher editor