Proctitis

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. Proctitis symptoms include rectal bleeding, diarrhea, discharge of mucus and tenesmus, a feeling or inability to empty the bowel upon defecation (likely a result of extensive rectal tissue fibrosis or possibly the formation of rectal strictures).They can begin as early as immediately following therapy (acute) or as late as after completion of radiation therapy (delayed or late). Acute proctitis symptoms can persist for up to 3 months, while delayed or late proctitis is a chronic disease that may continue for decades.

The most common therapies include 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.

Acute Radiation-Induced Proctitis

Biomodels offers acute rat and mouse models of radiation-induced proctitis. In this model 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. Animals receive one acute dose of radiation on Day 0 of the study and 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. Disease is evident at day 3, peaks near day 7 and persists through the final evaluation. 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.

Study Design Table

Acute Radiation Dose (Day 0) Proctitis Evaluation Duration Endpoints

20 Gy

Days 3, 7, 10.

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

 

Disease Course of Proctitis resulting from acute radiation exposure
Proctitis Endoscopy Images
Fractionated Radiation-Induced Proctitis

Biomodels also offers fractionated rat and mouse models of radiation-induced proctitis. Like in the acute model, 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. Animals receive 8 fractionated doses of radiation on days 0, 1, 2, 3, 6, 7, 8, and 9 of the study. Animals are evaluated daily for survival, body weight, evidence of bloody stool and diarrhea. On 6 of those days, animals are anesthetized and examined via video endoscopy to determine proctitis severity. Disease is evident the day after the final dose of radiation and disease severity typically peaks between days 10-15. 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.

Study Design Table

Fractionated Radiation Dose Proctitis Evaluation

Duration

Endpoints
4 Gy x 8 doses= 32 Gy
5 Gy x 8 doses= 40 Gy
6 Gy x 8 doses= 48 Gy

Days 10, 13, 16, 20, 23 and 28.

Disease typically peaks between days 10-15.

28 days Endoscopy score, Weight, Incidence of Diarrhea, Histology

 

Disease Course of Proctitis resulting from fractionated radiation exposure
Endoscopy Proctitis Images
 (A) Photomicrograph showing histological appearance of normal rectal mucosa. (B) Photomicrograph showing histological appearance of inflamed rectal mucosa.
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